The Glycine Miracle

The Science of Living Long

and Free from Inflammation

by

Joel Brind, PhD

WWW.OAKLEAPRESS.COM
The Glycine Miracle: The Science of Living Long and Free from
Inflammation © 2024 by Joel Brind PhD, all rights reserved.
 Table of Contents
Introduction ........................................................................ 4
Chapter One: Self-Experimentation Surprises ................ 7
Chapter Two: Amino Acid Relationships ......................... 16
Chapter Three: The Cells that Do Inflammation ...........23
Rend or Mend?
Chapter Four: The Inflammation Switch ........................ 40
Chapter Five: Red Flags ................................................... 49
Chapter Six: The Evolution of Cancer ........................... 56
Chapter Seven: The State of Life Science Research ...... 63
Chapter Eight: Anti-Inflammatory ................................ 68
Chapter Nine: Back to the Science, a Global
Hypothesis Regarding Glycine and Inflammation ......... 73
The Hypothesis
The Proof
Chapter Ten: How Does Glycine Deficiency
Result in Specific Disease States? .................................... 87
Chapter Eleven: Genetic Disorders Affecting
or Affected by Glycine ...................................................... 151
Chapter Twelve: Cutting Through TMI
on Chronic Disease ........................................................... 158
Chapter Thirteen: The Question of Biological Aging ... 170
Chapter Fourteen: Why Glycine? ................................... 182
References Cited .............................................................. 185
 Introduction
Americans spend more money than ever on healthcare,
so why does the average American seem less and less
healthy? Average American life expectancy has actually
started to go down in the last couple of years.
Putting aside the epidemic of obesity, even in child-
hood, the average American seems pretty healthy until
about the age of 40. But then the progression begins of
medications and surgeries that mark the decline in health
from age 40 on. Everywhere Americans are taking meds
for prediabetes and diabetes, high blood pressure, arthritis,
psoriasis and cancer, among many others. Many need to
undergo drastic interventions like knee and hip replace-
ments by the time they are 60, as well as cancer surgeries
and vascular surgeries like stents, bypasses and heart valve
replacements.
So the average American manages to hobble up to
about age 75 or 80 before he or she succumbs, usually to
some chronic illness like heart disease or cancer. Only a
minority of Americans actually can be said to die of old
age, even among those who may reach their nineties.
What’s wrong with this picture? Why don’t most
Americans live to be 100 or more, free of chronic illness
to the end?
4
 The Glycine Miracle
Many healthcare professionals, especially alternative
health advocates, believe the answer lies in correcting nu-
tritional imbalances, deficiencies or toxicities, and they are
right.
Most medical and medical research experts are now
coming around to the view that most chronic illnesses, in-
cluding cardiovascular disease, Alzheimer’s Disease and
Cancer, are the result of chronic inflammation. They are
also right.
The experts also believe that the problem is very com-
plex, due to a complex interplay of genetic, environmental
and dietary factors. Here, they are wrong.
Many years ago I learned that when an expert claims
that the problem is complex, he really means that he does
not know. Complexity then, is often a euphemism for ig-
norance, but one which preserves the outward appearance
of wisdom and expertise. Great discoveries are made when
a simple yet fundamental truth is revealed, in the face of
which the experts dissolve away. Thus the many experts in
different modalities of treating the dreaded scourge of
syphilis less than a century ago, disappeared with the dis-
covery of penicillin, just as many complex theories of
physics disappeared with the elegant simplicity of e = mc2.

5
 The Glycine Miracle
This book is written to share the discovery of the great
and simple truth that has been revealed to me through my
scientific research, which has been my profession for more
than half a century. This truth solves the mystery of
chronic illness and early demise that currently plagues our
society.

6
 Chapter One
Self-Experimentation Surprises
It was a picture perfect day for baseball. It was back in
2010 in the new Yankee Stadium in New York, and a great
day to be wearing my shorts and my NY Yankees tee shirt
as the morning chill gave way to the warming mid-June sun
in the cloudless blue sky. It was my first time in the new
stadium, there with some of my family, as my brother-in-
law had scored some really good box seats a few rows be-
hind the first base dugout. As a life-long Yankee fan—as
my father had been—I was thrilled to watch the game.
And once the game started, I was totally absorbed—espe-
cially because the Yankees were winning, and the view was
wide and totally unobstructed.
Of course, the sun was also totally unobstructed, and
sometime during the fifth inning—about an hour and a
half into the game—I noticed a warm sensation on my
thighs. I looked down and came to the sudden realization
that I was red as the proverbial boiled lobster, everywhere
that my fair skin was not clothed. From the hem of my
shorts down to my socks, my whole arms and from the
neck up, I was sunburned as I had not been since at least
my twenties. You see, the thought of putting on sunscreen

7
 The Glycine Miracle
or sunblock had never even occurred to me in preparation
for this day. After all, I wasn’t going to the beach!
I immediately segued to a seat in a shaded area some
rows back, but I knew, I mean I knew, with 100% cer-
tainty, that for the next couple of days, even the simple
tasks of dressing, undressing and bathing would be excru-
ciating. And after all that, the dead skin would just blister
and peel off, without even leaving the benefit of any sig-
nificant tanning. I knew this because I had done this to
myself several times during my youth, that is, I had gone
to the beach and been exposed to the sun for an hour or
two or more, with inadequate sunscreen.
This time would be no different, I was certain. And I
forgot all about the game. I’m pretty sure the Yankees won,
but I don’t remember anything else about the game, or
even much about the interaction with my family there that
day. In fact, there was nothing really memorable that hap-
pened. But what didn’t happen was truly a game changer.
You see, during that time I was in the process of con-
ducting an experiment on myself. Starting in 2008 I began
taking, as a dietary supplement, 10 grams per day of the
amino acid glycine. Exactly why I decided upon this ex-
perimental dietary regimen will be explained a bit later in
this book. The fact is, I did not know quite what to expect.

8
 The Glycine Miracle
I really didn’t expect anything dramatic to happen. Rather,
I had come to the idea that taking that much glycine every
day should be of some long-term health benefit, and that
it certainly would do me no harm. After all, glycine, the
simplest of all the amino acids, is a bulk nutrient of which
everyone takes in a quantity of some number of grams per
day. Glycine is also such a small, water-soluble molecule
that it cycles through the body in a matter of hours; it does
not build up in the long term to any sort of toxic level. I
also knew that the typical diet contains about two to three
grams per day of glycine, so that, in order to make a sig-
nificant difference, only a big amount like an additional
ten grams per day could be expected to have any notice-
able effect.
So, in order to embark on this experimental regimen,
I first needed to figure out how to formulate an amino acid
powder in such a way that I could easily take 10 grams a
day. Glycine is available in capsule form from a number of
health food suppliers online. But I would need to take six-
teen 500 mg capsules, or eight one-gram capsules every
day. That seemed to me too much like a chore. But I had
noticed early on, when trying things out informally, that
glycine has a sweet taste, albeit with an unpleasant after-
taste. (The name glycine is derived from the Greek, mean-

9
 The Glycine Miracle
ing “sweet amine”). I found that the taste was considerably
improved when cut with sugar, or added to something like
fruit juice which contains natural sugar. Since gelatin also
has a high content of glycine in protein form, I settled
upon a “glycine Jell-o”-type formulation, wherein each
(four-ounce) serving would provide about half a gram just
from the gelatin. Then, to unflavored gelatin, I would add
natural tart cherry juice. Of course, the cherry juice has its
own natural sugar, but since it is naturally tart one could
add quite a bit of sweetness without making it too sweet.
So my daily regimen ended up being a home-made gelatin
dessert, just following the directions on the unsweetened
gelatin box with tart cherry juice, only adding 9.5 grams
per serving of pure glycine powder. It was a good-tasting
dessert and was thus no problem eating it once a day, day
after day after day, religiously.
Now, back to the ball game and the sunburn. As I
quickly moved to a shady seat to watch the last few innings
of the game—having made suitable apologies to my
brown-skinned family for the need to do this—I kept
beating myself up over how I could have been so stupid as
to let this horrible sunburn happen. But as I settled back
to watching the game, I soon forgot about the sunburn. In
fact, by the time the game was over and we were leaving

10
 The Glycine Miracle
the ballpark, the redness had already diminished notice-
ably. And in the succeeding hours, it just continued to fade,
and was completely gone—except for just a little bit of
tan—by the next morning.
By this time I had read enough about glycine to know
that it has some benefit in terms of inflammation. This
knowledge was largely amassed by a prolific research team
at the University of North Carolina (UNC) headed by a
toxicologist named Ron Thurman. Dr. Thurman had un-
fortunately passed away in 2001 at the age of only 59, from
a massive heart attack. Although there were several papers
that were published during the ensuing several years, the
work at UNC did not continue—as far as I know—and
other members of the team were scattered elsewhere.
The Thurman group laid the groundwork for under-
standing glycine as the immune system’s own natural reg-
ulator of inflammation. Until then, glycine—acting as the
free amino acid, rather than as a building block of protein
molecules—was understood to be an inhibitory neuro-
transmitter in the central nervous system (CNS, i.e., brain
and spinal cord). As an inhibitory neurotransmitter, it pre-
vents hyperactivation in neural pathways. That’s why
glycine supplements have traditionally been sold as sleep
aids. It doesn’t make you sleepy, but it can help allow you

11
 The Glycine Miracle
to get to sleep more easily. What the Thurman group
found was that the very same molecule on the cell surface
membrane of the CNS neurons (nerve cells)—the glycine
receptor—was also to be found on the surface of
macrophages (the immune cells that actually generate in-
flammation). They found that the activation of
macrophages to produce inflammation was inhibited by
adding adequate concentrations of glycine to the cellular
environment. The work of the Thurman group was pub-
lished in a review published in 1999. More on their work
later in this book.
What’s important for now is the fact that—as I real-
ized by doing some reading in the medical literature to re-
fresh my knowledge on skin physiology, and having done
research on the skin during the 1970s and 80s—the painful
and damaging aspects of sunburn are actually the result of
inflammation; the immune system’s reaction to the sun-
burn, rather than the sunburn itself. When you think
about it, it really does make sense. After all, if the sun just
makes your skin turn red, why doesn’t it just go away when
the offending stimulus—intense sunlight—is withdrawn?
What is the point of all that pain and damage that happens
in the succeeding hours and days?

12
 The Glycine Miracle
So what did not happen to me this time around was,
to say the least, a big surprise. In fact it was one of two big
surprise findings in my grand self-experiment with glycine.
A bit later that summer, in early July, we were scrambling
to finish some work in our house to make it suitable to put
up several family members for a couple of days, as our
daughter was set to get married at the end of the month.
In particular, I needed to finish a bit of drywall work
in the basement. It only required two or three sheets’
worth of drywall, but drywall comes in 4-foot by 8-foot
sheets, too big to fit into our SUV. The best way around
that problem was to make some measurements such that
the drywall could be cut in the store into smaller pieces.
So my wife and I went to our local Home Depot with a
tape measure, a yardstick, a pencil and utility knife. The
drywall was stacked up on the concrete floor to a height
of about 4 feet. I would climb onto the top of the stack,
measure and mark the top sheet for the cuts, score the
cuts and break the cut pieces, finish the cuts with the knife
and pass down the cut pieces of drywall to my wife. Then
I would jump down to the floor and the two of us would
load each piece onto the cart. This process would be re-
peated until we had all the pieces we needed to be cut, cut.

13
 The Glycine Miracle
Except I did something wrong. I must have gotten mo-
mentarily distracted and turned away from the sheet of
drywall I was cutting, and accidentally stepped right off
the stack. I fell the full four feet down onto the concrete
floor directly onto my tailbone! My wife looked on in hor-
ror, speechless, but already imagining the trip to the ER
that would surely ensue. And it hurt like hell! But only for
about half a minute, after which the pain subsided enough
for us to finish what we were doing, load the drywall into
the SUV and drive home.
Trouble is, we were under a bit of time pressure that
afternoon, as we had bought tickets to a dinner dance that
evening. So we went to the dinner-dance anyway, and sur-
prisingly, my injuries were not bothering me that much. So
I thought we could try a dance or two, and in fact, it was
no trouble at all. More surprisingly, I experienced no pain
whatsoever the next morning. Fortunately, I had evidence
of the very serious fall I had suffered, in that I did develop
a massive bruise on my lower back, and that bruise took a
week or so to go away.
So there were no two ways about it: Between the sun-
burn and the fall at Home Depot, I had experienced two
events that should have produced massive inflammation,
with all the accompanying pain and disability. But they did-

14
 The Glycine Miracle
n’t. And I don’t think in my entire career as a scientist that
I have ever had any experiment produce such dramatic and
definitive results: Inflammation, always known to every-
one to be a normal consequence of injury, did not happen
after these very substantial injuries.
Now the big question, what did these dramatic results
mean?

15
 Chapter Two
Amino Acid Relationships
My graduate degree is a PhD in Basic Medical Science,
with specialization in biochemistry, physiology and im-
munology. Inflammation is a function of the immune sys-
tem, and thus within the purview of immunology, but my
entry into the study of glycine actually began in the arena
of nutritional biochemistry and aging.
During the early years of this century, in addition to
my full-time professorship at Baruch College (City Uni-
versity of New York), I was working part-time as a bio-
chemist consultant for the Orentreich Foundation for the
Advancement of Science (OFAS), a private non-profit re-
search organization for which I had worked full time back
in the early 1980s. Other researchers at OFAS had been
doing research on the essential amino acid methionine
since the early 1990s. In 1993 they published a paper de-
scribing the significant extension of normal lifespan of lab-
oratory rats, merely by restriction of the methionine
content of the diet they were fed. Since methionine is an
essential amino acid, the animals would not survive a diet
completely devoid of methionine, but if you gave them just
enough to sustain life—while feeding them ad libitum (i.e.,

16
 The Glycine Miracle
to eat all they wanted)—they would live 30-40% longer
than rats fed the normal control diet. The restriction
needed to be severe—about 80% less than normal methio-
nine content—such that, although the rats lived substan-
tially longer, they did not grow to normal adult size.
Hence, they stayed pretty much the same size they were
when weaned, which was when they were started on the
methionine restricted (MR) diet.
The original experiment showing lifespan extension by
methionine restriction (MR) turned out not to be a one-
off, but the first of many papers on rats and mice by the
OFAS group and others in the field. By the early years of
this century, MR had been established as a real phenome-
non. But the basis of MR remained a mystery. Part of my
job was to solve the mystery, and that was my start on the
road to glycine.
At this point it would be useful to expand a bit on
amino acids in general, to provide some perspective on the
connection between these two: glycine and methionine.
Most people are familiar enough with the fact that amino
acids are the building blocks of proteins. They are small
molecules that fit together like Lego blocks, with 20 dif-
ferent ones altogether making up the full variety of all pro-
teins in the body. With the variety provided by the 20, the

17
 The Glycine Miracle
diversity of protein structures and functions that can be
made is almost limitless. There is the wide array of en-
zymes—proteins that function as “nano” machines that do
all manner of chemical work, structural proteins such as
collagen—the actual “threefold cord” with which the body
is knit together, transport proteins that carry various fats,
vitamins and minerals through the bloodstream to the var-
ious cells and tissues of the body, hormones that carry mes-
sages from one part of the body to another, and a host of
others. Twelve of these amino acids are considered “non-
essential,” since the body (mainly the liver) can make them
from simpler compounds, and eight of the amino acids are
considered essential, because the body cannot make them
from simpler compounds, and thus needs to obtain them
from the diet.
There is in the field of nutrition, however, a tendency
to oversimplify the amino acids, as if their role in consti-
tuting proteins were their only function. In classifying
them as essential v. non-essential, their importance in the
diet is also oversimplified. Thus there is the pervasive con-
cept of “high quality protein,” a term applied to a protein
source which is particularly rich in the essential amino
acids. Not surprisingly, these have gotten most of the at-
tention in terms of dietary research over the years. Hy-

18
 The Glycine Miracle
potheses concerning the origins of many disease states
have sought to find deficiencies in essential amino acids—
such as methionine—being responsible for such condi-
tions as cancer. After all, why would anyone waste time and
resources studying nutrients that are non-essential?
But all amino acids are not alike, and the “essential” v
“non-essential” designation is an oversimplification which
can be misleading. Methionine restriction being a good
thing is one glaring example of this. Amino acids, you see,
serve not only as the building blocks of the proteins. They
also serve many other functions, such as being intermedi-
ate compounds in the transformation of one amino acid
into another, and also building blocks of other, non-pro-
tein substances such as DNA. And some amino acids—
even just among the essential ones—are more critical than
others. Thus it has long been known that methionine has
a critical function as the universal methylator; a donor of
one-carbon units in the synthesis and modification of
many different substances such as DNA, neurotransmit-
ters and other types of compounds. Because of its impor-
tance and its essential nature, the body has a number of
redundant mechanisms for the recycling, salvage and re-
generation of methionine. The methionine cycle, for ex-
ample, is well known to all students of biochemistry. But

19
 The Glycine Miracle
precisely because the body is so frugal in its use of methio-
nine, it actually needs very little of it: about 300-500 mg
per day; more like the daily requirement for a vitamin
rather than a bulk nutrient like an amino acid. And the dis-
tribution of methionine in animal proteins is quite asym-
metric, with muscle being very methionine-rich, and the
collagen of the bones and connective tissues being very
methionine-poor. Hence, muscle meats are universally
considered “high quality protein,” whereas collagen
(gelatin) is considered a very low quality protein.
Now take a look at the modern, Western diet, with the
typical bacon-and-eggs breakfast, tuna fish or meat loaf
sandwich lunch and steak or chicken dinner, seven days a
week, and you note that it is extremely methionine-rich.
Unfortunately, excess methionine is not harmless, and the
body gets rid of it as a toxin when there is too much. Re-
search over the last 20 years has demonstrated that when
one consumes a typical high methionine meal, the liver ac-
tually does the opposite of its methionine conservation
routine, and gets rid of the excess methionine quite rap-
idly. But there’s a catch. While the liver has many pathways
available to conserve and recycle methionine, it has only
one pathway to get rid of the excess. This makes sense
when one understands that the body is designed to better

20
 The Glycine Miracle
withstand famine than feast. And it turns out that the only
pathway for methionine clearance uses up two molecules
of glycine for every one molecule of methionine cleared.
That would not be a problem of course, were glycine ac-
tually non-essential. But that turns out not to be the case.
(Much of the biochemistry was worked out in detail in the
early years of this century in the laboratory of the late em-
inent biochemist Conrad Wagner at Vanderbilt University
in Tennessee.)
You see, in addition to all the various biochemical func-
tions of glycine, including its role as a building block for
proteins, it also has a function that is not really biochem-
ical, meaning that it does not participate in this role, in
any biochemical reactions. Specifically, glycine acts as a
regulator of cellular function by stabilizing the cell mem-
brane of several types of cells—most importantly, all the
various types of macrophages, the cells of the immune sys-
tem that generate inflammation. Importantly, for this reg-
ulatory function, the concentration of glycine in the blood
plasma and the fluid that bathes all the cells of the body,
needs to be at least three or four times higher than the
concentration needed to make all the proteins that glycine
is a part of.

21
 The Glycine Miracle
As a consequence of eating the typical high animal pro-
tein meal (rich in muscle meats and poor in bone and con-
nective tissue, that is), the body actually loses glycine.
Hence, the blood plasma of meat-eaters contains less
glycine than that of vegans or vegetarians, even though the
total consumption of glycine (and all the other amino
acids) is higher. (It is an interesting commentary on the
overall state of medical science to note that when this dif-
ference was confirmed by Schmidt, et al., a group at Ox-
ford University, and published in 2016, the authors found
it counterintuitive, and could not explain it! More on this
in Chapter Six).
Getting back to the question of exactly why methion-
ine restriction should extend life, my thinking took a dif-
ferent tack than the one generally followed. Specifically, I
thought, “Why do we think of an experimental diet result-
ing in longer-lived animals to be an extension of lifespan
at all?” Rather, why not consider that the shorter-lived an-
imals have their natural lifespan cut short by whatever it
is—or isn’t—in the control diet that makes them die
sooner than those animals on the experimental (in this
case, methionine-restricted) diet?

22
 Chapter Three
The Cells that Do Inflammation
What exactly is the nature and purpose of inflamma-
tion? Inflammation may well be the most familiar function
of the immune system, inevitably popping up with any sort
of injury, for example. Its classic description goes back cen-
turies in the medical textbooks, i.e., “rubor, et tumor et
calor et dolor” (Latin for redness and swelling and heat and
pain). When occurring at any joint, immobility is added to
the list of symptoms. And of course everybody knows that
the first aid treatment for blunt injury is to put an ice pack
on the injured area, for the express purpose of suppressing
inflammation. This bit of common wisdom raises an inter-
esting question, namely, why does the body normally re-
spond to injury in an inappropriate way, such that this
natural response—inflammation—needs to be suppressed?
Perhaps this response is not so natural after all, rather sug-
gesting some underlying disorder?
Now that medical science has elucidated bodily func-
tions at the cellular and biochemical level, we can take a
closer look at what actually happens in inflammation. In
terms of the immune system, inflammation is seen to be a
function of what is called innate immunity, i.e., a rela-

23
 The Glycine Miracle
tively non-specific response to infection or cellular dam-
age. The body needs to respond to infection quickly and
vigorously, lest the invading microbes spread and multiply
and kill the host before a specific antibody response—
which takes weeks to muster—can be mobilized. Biochem-
ically, that response includes the manufacture and
deployment by the immune system of a host of toxic
chemicals (collectively known as cytokines) which can kill
the invading microbes. But since these chemicals are non-
specific poisons, they also do damage to normal bodily tis-
sues. This manifests in part, as the above-described
familiar symptoms of inflammation. This response thus
raises another interesting question, namely, what is the
point of secreting poisons to kill invading microbes in cir-
cumstances where there are no microbes to kill, such as in
blunt injury? One common hypothesis suggests that the
immobility of injured joints protects the joint from further
injury; sort of a natural cast or splint. Indeed it is generally
thought that inflammation is part of, or essential for the
initiation of the healing process. The trouble is, all those
cytokine poisons actually inhibit healing. So there is really
no satisfactory explanation out there for why the body es-
sentially engages in a self-destructive process in response
to injury. Indeed, the big hunt is on for an explanation as

24
 The Glycine Miracle
to why inflammation seems to happen chronically, often
seemingly for no reason at all. A recent review on the sub-
ject of chronic inflammation in the popular journal Epoch
Times describes the situation thus: “When the body is in-
fected or injured, inflammation—often likened to fire—is
nature’s way of burning away pathogens and repairing dam-
age. Once the threat is eliminated, inflammation should
subside. But if the fire continues to smolder, it can become
a chronic issue.” Here is embodied the central contradic-
tion: How can we speak of inflammation as a proper re-
sponse to injury, but one which needs to subside “once the
threat is eliminated,” if there is no threat to begin with?
So it is clear that the wrong question—i.e., “Why does in-
flammation persist after the initial response?”—is being
asked. To answer it, a distinction is made between “normal
inflammation” and “chronic inflammation,” the latter of
which is inflammation that persists more than three
months. But this distinction is arbitrary and artificial. As
we shall see later in this book, short-term inflammation,
when inappropriate, can be just as damaging—even fatal—
as chronic inflammation.
But at least it is now widely understood that inflamma-
tion is the common denominator for most of the chronic

25
 The Glycine Miracle
diseases that make people sick and die these days, from
arthritis to diabetes to cardiovascular disease to cancer.
So let’s take a look at the cellular players in the inflam-
matory process. The cells that actually generate inflamma-
tion are the immune system’s first responder cells,
collectively called macrophages (derived from the Greek,
meaning “big eaters”). These cells all originate in the bone
marrow, where all of the red and white blood cells origi-
nate. The name macrophage refers to these cells acting like
amebas, eating up dead and dying cells and cellular debris
and invading microbes by the process of phagocytosis.
Phagocytosis is the process in which the cell doing the eat-
ing actually moves its membrane and cytoplasm around to
engulf large particles. Once engulfed, the contents of the
newly formed food vacuole are digested by cellular en-
zymes and chemically recycled, if they are digestible. If
these particles are not digestible, they simply remain in-
side the macrophages permanently. This is the case, for ex-
ample, of the pigment particles used in tattoos. The fact
that the macrophages remain alive and therefore capable
of some movement, is why tattoo images gradually become
blurred with time.
Several types of macrophages circulate as white cells
in the blood (i.e., some of the monocytes, but for simplic-

26
 The Glycine Miracle
ity, I also include the more abundant white blood cells
called neutrophils, as well as basophils and eosinophils in
the macrophage category), and there are also macrophages
which are resident in perhaps all the organs and tissues of
the body, at least wherever they have been looked for.
Hence, there are known to be macrophages specific to the
liver and the lungs and the bone and the skin and the brain,
for example. And even though these macrophages typically
look like the cells of the organs in which they are resi-
dent—save for chemical surface markers by which they can
be distinguished chemically—they all originate in the bone
marrow, migrating to the other organs during the embry-
onic stages of life.

Rend or Mend?
The macrophages thus comprise the immune system’s
first responder cells, and they get activated whenever the
chemical signature of a disease-causing microbe is de-
tected or anytime there is any tissue damage (cellular
death). But their activation is often misunderstood. Re-
cent research has demonstrated that macrophages can be
activated in two ways: one level of activation causes them
to migrate to the site of injury and phagocytize the dead

27
 The Glycine Miracle
cells and cellular debris. Macrophages which are activated
to engage in this activity are typically referred to as “M2.”
But it takes a different, second type of activation, typically
referred to as “M1” (sometimes called “priming”) which
causes them to initiate the process of cytokine production
and secretion characteristic of inflammation. To reflect
this dichotomous type of activation, we may refer to M1
as “rend” mode, and M2 as “mend” mode. So is a
macrophage involved in dealing with tissue injury there to
rend or to mend?
A good metaphor for the action of macrophages is the
action of first responders in society. For example, when
there is an accident on a freeway or expressway, the first
responders that show up are the police. They arrive at the
scene of the accident, call in backup and ambulances and
tow trucks, take accident reports from witnesses and redi-
rect traffic to keep it flowing. When their work is complete,
they return to their nearby bases and traffic flow returns to
normal. These would all be considered “mending” actions.
Of course, being police, all the while they are armed with
deadly force—capable of rending, rather than mending—
but would not think to draw their weapons and start shoot-
ing unless bad actors are present. But just imagine if every
time there was an accident on the highway, the police

28
 The Glycine Miracle
showed up and started shooting? That would be insanely de-
structive! Yet that is exactly what happens within our own
bodies even when there are no bad actors present, i.e., in-
jury—and therefore inflammation—in the absence of infec-
tion. No wonder people’s physical health begins to go
downhill by the time half a normal lifespan has been lived!
But there is much more to the story of what actually
happens in inflammation, some of it only elucidated in the
last couple of years. As noted earlier, inflammation is ba-
sically a nonspecific reaction to the detection of the chem-
ical signature of any type of dangerous microbe. But it is a
multifaceted and graded reaction, involving several differ-
ent types of weaponry. It is not necessary here, however,
to get too much into the weeds, so to speak, of all the di-
verse different types of cytokines; chemical effectors of
damage to microbes, some of which are not fully under-
stood. Suffice it to say that macrophages engage in the
equivalent of shooting a gun, but it may also escalate to
the equivalent of artillery and ultimately, the equivalent of
a nuclear weapon!
The simplest action of an M1 activated macrophage is
the secretion of molecular “bullets:” small, destructive
molecules such as hydrogen peroxide. If you look at a bot-
tle of hydrogen peroxide you can purchase at a pharmacy,

29
 The Glycine Miracle
it is to be used as a topical antiseptic; not to be taken in-
ternally. But internally, M1 macrophages actually secrete
hydrogen peroxide for the same purpose: killing microbes
that have gotten into the body. These small molecules are
secreted by being produced in the macrophage in small
vesicles; little bubble-packets that migrate to the cell
membrane, with the contents being released into the ex-
tracellular space when the membrane of the vesicle fuses
with the cell membrane, both membranes having the
structure of highly specialized “soap bubbles.” There are
other, larger effectors of inflammation, cytokine proteins
such as Tumor Necrosis Factor alpha (TNFα). TNFα is
produced in the cell as a protein molecule that also ends
up in a vesicle that fuses with the cell membrane, and it
can activate other immune cells by contact with such cells,
and it can also have its active part clipped off so that the
resulting soluble TNFα is secreted into the fluid outside
whence it can migrate to activate other cells elsewhere in
the body.
And then, for a greater inflammatory response, there
is the construction of an ‘artillery piece’ called an inflam-
masome within the macrophage. An enzyme called caspase
within the cell initiates the construction of a very large,
multi-protein complex in the shape of a cylinder. Activated

30
 The Glycine Miracle
by another enzyme in the cell called a gasdermin (gasder-
min D being the most well studied type), this inflamma-
some creates a large cylindrical pore in the cell membrane,
a literal artillery barrel large enough (10-20 nanometers in
diameter) to enable the bulk flow outward of fairly large
inflammation effectors such as Interleukin 1beta (IL-1β).
IL-1β, for example, has long been known as a pyrogen; a
substance which can induce a body-wide fever, for the pur-
pose of killing infecting bacteria.
As you might guess, a number of such large pores in the
cell membrane can be pretty destabilizing to the integrity
of the macrophage. Such large openings in the cell surface
formed by gasdermin D allow for the bulk passage of water
molecules, for example. In the bloodstream, the presence
of high concentrations of albumin and other proteins keeps
these cells from swelling and bursting. But within the tis-
sues outside the bloodstream, where the cells are bathed
in essentially protein-free lymph, water flows in, ultimately
leading to the cells bursting (which we may liken to the det-
onation of a nuclear weapon), a process that is termed py-
roptosis, and releasing a huge torrent of cellular contents
(often referred to collectively as “DAMPS” for “damage-as-
sociated molecular patterns,” which tremendously exacer-
bate the inflammatory reaction.

31
 The Glycine Miracle
This sort of reaction has long been known to occur in
severe infectious reactions. It was first observed in 1986
by Arthur Friedlander at the US Army Medical Research
Institute in Maryland, who demonstrated the ability of an-
thrax lethal toxin to directly destroy macrophages. In 1992
the process was observed in detail by A Zychlinsky of the
Pasteur Institute in Paris, Fance, as the induction of sui-
cide in human intestinal macrophages by Shigella flexneri
bacteria. First presumed to be an example of a well known
process of programmed cell death, called apoptosis, the
different mechanism by which this cellular suicide occurs
was recognized in 2000 and termed pyroptosis by Brad
Cookson and Molly Brennan of the University of Wash-
ington in Seattle, who worked with Salmonella ty-
phimurium bacteria. Pyroptosis is maximal and
widespread in septic shock, a condition in which an infec-
tion has spread to the entire bloodstream, and by provok-
ing the rupture of many macrophages and the release of
so many DAMPs, is usually rapidly fatal.
Now this begs the same question we entertained ear-
lier, namely, why does the immune system generate a reac-
tion so destructive that it can kill the whole body itself?
Actually, such a violent reaction is appropriate for virulent
bacterial infections like Salmonella and anthrax, but septic

32
 The Glycine Miracle
shock does not usually result because the process is some-
how self-limiting. How? Surprisingly, the answer is exactly
the same answer that applied to the initiation of inflam-
mation in the case of injury without infection (sterile in-
jury). Again, it is a matter of the concentration of the
amino acid glycine!
Just as the Thurman group at UNC had elucidated the
role of glycine in the initiation of inflammation via the
glycine-gated chloride channel called the glycine receptor,
another research team had been investigating, since the
1980s, the protective role of glycine in septic shock. Thus,
nephrologist Joel Weinberg and his group at the University
of Michigan determined that glycine’s protective effect in
septic shock does not involve the glycine receptor. But the
molecular details of this effect has only become clear from
research in the last couple of years, at several major re-
search centers, including that of the pharmaceutical com-
pany Genentech in San Francisco, CA.
It turns out that, contrary to the prevailing dogma for
decades, the swelling and bursting of the macrophages is
not a passive process owing to the pressure of inflowing
water. Swelling, yes, but this does not lead to the bursting
of cells without the action of another surface protein
called “ninjurin 1” (NINJ1). When Nobuhiko Kayagaki

33
 The Glycine Miracle
and colleagues at Genentech tested laboratory mice from
which the NINJ1 genes had been removed (called NINJ1
knockouts), the final step in pyroptosis did not occur; the
nuclear weapon did not detonate. In order for the final
step of membrane rupture to occur, the NINJ1 protein
molecules which normally float within the cell membrane
must aggregate together, and glycine prevents that from
happening.
This is really quite an astonishing discovery: The lowly
“nonessential” amino acid glycine is the very molecule
which specifically prevents both the very first step (via the
classical glycine receptor) and the very last step (cell mem-
brane rupture, or CMR) of the inflammatory response, so
that inflammation is not excessive or inappropriate, unless
of course, glycine is deficient. Hence, glycine is both the
alpha and the omega of the control of inflammation!
But a related question then arises, namely, how is py-
roptosis—which can happen appropriately to combat in-
fection from such pathogenic bacteria as Salmonella and
anthrax—ever limited in a body that is glycine-deficient,
such that it does not invariably escalate to a life-threaten-
ing scenario like septic shock? After all, pyroptosis causes
the release of inflammatory mediators which dramatically
accelerate damage, so if glycine is low, what stops the sit-

34
 The Glycine Miracle
uation from spiraling out of control? You may find this sur-
prising; even counterintuitive, but the answer is still
glycine! How, exactly, you might ask?
It turns out that all living cells normally concentrate
glycine from the surrounding fluid. That is, cells expend
energy to pump glycine in, such that the normal concen-
tration of glycine inside of cells is five to ten times higher
inside than outside. Hence, when a macrophage “goes nu-
clear,” i.e., when the cell membrane ruptures and releases
inflammatory mediators (DAMPS) all over the place, it
also substantially increases the local extracellular concen-
tration of glycine. The increased concentration of glycine
therefore acts to stabilize other macrophages, both pre-
venting the final stages of pyroptosis, and stabilizing the
membranes of unactivated macrophages via the glycine re-
ceptor. Finally, the system fails and results in septic shock
when glycine concentration is so low, and/or the infection
has become so massive, that inflammation passes the point
of no return.
Later, we will revisit the work of Joel Weinberg on the
subject of how glycine prevents cellular necrosis, a process
that is not caused by inflammation, but other insults such
as oxygen deprivation. But as we will see, it is virtually the
same process of cellular death by necrosis in the kidney

35
 The Glycine Miracle
cells that Weinberg, et al., study, which happens in pyrop-
tosis in macrophages. In other words, the final detonation
and self-destruction that characterizes the ultimate step
in inflammation, is really the same process in the death of
kidney cells by necrosis. Importantly, the sudden release
of cellular contents in necrosis or pyroptosis causes inflam-
mation to be generated in the vicinity of the event. In fact,
this is the kind of cellular demise that happens in septic
shock, which causes multiple organ failure from massive
cell death. The Thurman group demonstrated the ability
of glycine to prevent septic shock in animals back in the
1990s, and the Weinberg group demonstrated the protec-
tive effect of glycine in cellular necrosis back in 1987!
All of this action I have summarized here has been the
subject of astonishing amounts of research in the last few
years. For example, merely using the search term “pyrop-
tosis” in review papers—papers which review the findings
of many primary research studies—generates 531 hits—531
separate, unique review papers—in the National Library
of Medicine (Medline) database! And as we have seen, the
knowledge base relating to inflammation and glycine has
been expanding rapidly. Hence one might think the real-
ization of the central importance of glycine and glycine
deficiency in human health and disease would be immi-

36
 The Glycine Miracle
nent. I, for one, certainly hope that it is, and the very pur-
pose of this book is to hasten that day.
Indeed, we may now distill recent discoveries about
cellular death and macrophage function to essentially two
mechanisms:

1) Apoptosis, which is the orderly condensation of cel-

lular contents into “bite-sized” pieces of molecular aggre-
gates, and the emission of signals to attract macrophages
and to activate them to the “mend” or M2 mode. The M2
macrophages then quietly devour the remains of the cell,
clearing the way for the normal functioning of the tissue.
2) Pyroptosis (or a similar type of cell death, such as
necrosis or ferroptosis), which, as described earlier in this
chapter, is the swelling and explosive bursting of the cell,
spewing its contents willy-nilly in the vicinity, and attract-
ing and activating macrophages to the “rend” or M1 mode,
propagating and magnifying the inflammatory state. This
is what results in chronic inflammation, with its resulting
pain and tissue damage and even malignant tumor gener-
ation, or blood vessel blockage, depending upon where in
the body it occurs.

37
 The Glycine Miracle
When glycine concentrations are adequate, pyroptosis
only occurs in a limited way in response to a virulent in-
fection. But when glycine concentrations are too low, py-
roptosis occurs inappropriately in response to sterile
injury, and excessively even in response to infection, lead-
ing to chronic inflammation and some form of early de-
mise of the whole body.
Unfortunately, as we have also seen in earlier chapters
of this book, the focus of researchers is typically pharma-
cological rather than physiological. In other words, rather
than studying a disease process in order to understand nor-
mal function and to learn how normal function may be re-
stored, disease processes are studied in order to develop an
artificial method—a drug—to correct the diseased condi-
tion. A particularly instructive example of this sort of think-
ing, from the Cookson et al. group at the University of
Washington, is embodied in the literal bottom line of a
study by Wendy Loomis et al. (including Brad Cookson) on
the action of glycine to prevent the final stage of pyroptosis:
“Glycine administration is highly protective in models of
sepsis, suggesting that understanding the mechanism of
glycine action may provide novel therapeutic targets for in-
flammasome-mediated pathology. This study identified novel

38
 The Glycine Miracle
pyroptotic cytoprotectants of much higher potency than
glycine, which may be useful for future studies of pyroptosis.”
That makes me ask the following question: If glycine,
a normal and natural component of the blood plasma and
lymph, is the natural regulator which arrests the process
of septic shock, why look for something of greater po-
tency? This is not to belittle the importance of the study
in helping to characterize and understand the nature of
glycine’s action in this process, but the focus seems rather,
as we have seen before, to come up with new drugs. And
after all, as discussed a bit earlier here, the final piece of
the puzzle of the glycine mechanism was discovered in the
laboratories of a pharmaceutical company (Genentech).

39
 Chapter Four
The Inflammation Switch
A great deal of medical research attention is focused
on the question: “What is responsible for inflammation
becoming chronic and thus doing damage and causing
chronic disease?”
Unfortunately, this bypasses our earlier question about
why the body resorts to inflammation in the first place in
situations—e.g., blunt injury—when it cannot possibly do
any good, and only causes harm. In other words, inflam-
mation is taken as a given in such circumstances, and the
dismissal of the real question precludes its ever being an-
swered! (Later in this book, the scientific process itself will
be discussed, and the importance of asking the right ques-
tions will loom large.) For me, the surprise of not experi-
encing inflammation when it had been expected as a
certainty, forced me to question my basic assumptions.
To examine this question about the switch that turns
inflammation on and/or keeps it on inappropriately, we re-
turn to the seminal research of Dr. Thurman’s group at
UNC in the late 1990’s. It was the Thurman group that
elucidated the likely mechanism by which glycine acts to
prevent the inappropriate or excessive priming of

40
 The Glycine Miracle
macrophages, rather like a trigger lock in our first respon-
ders metaphor. To understand this process more specifi-
cally, I need to introduce some basic knowledge of cells
and cellular physiology.
The cell is the microscopic functional unit of a living
organism. Indeed, some organisms—like amebas—consist
of just a single cell. In fact, every living body—including
the human body—starts out life on earth as a single cell at
the time of fertilization or conception. Then it grows by
cellular division and specialization. A fully grown human
body is composed of some 100 trillion cells of some hun-
dreds of different types, ranging from the epithelial cells
of the skin to the various types of blood cells, muscle cells,
nerve cells and so on, including all the various types of
macrophages of the immune system. The boundary of
every cell is formed by what is called the cell membrane
or plasma membrane, which differentiates the inside from
the outside of the cell. So for example, the blood plasma
constitutes the outside environment for all the blood cells.
The membrane itself is very fluid and constantly changing,
to enable the cell to function in and adapt to its surround-
ings, and to respond to messages from other parts of the
body and other cells nearby. Its structure consists of a
soapy film, with highly diverse and specialized molecules

41
 The Glycine Miracle
floating around in it. Thus, it is rather like a highly com-
plex and specialized soap bubble. Each cell contains within
it a nucleus, which contains the DNA; the library of in-
formation that specifies everything the cell is capable of
making in terms of proteins. Various proteins comprise the
cellular machinery itself and everything the cell can make
for export for use outside the cell, such as hormones and
cytokines. “Organelles” within the cell, called mitochon-
dria, function as power plants to generate the chemical en-
ergy the cell requires. Other organelles include
ribosomes—which are basically protein knitting machines,
endoplasmic reticulum—which are assembly lines com-
posed of many ribosomes, and proteasomes—which are
basically protein recycling centers. There are also other or-
ganelles that perform various functions. The proteins and
other molecules that float around within the cell mem-
brane itself, determine the exchange of materials and mes-
sages between the inside and the outside of the cell. Every
living cell must maintain what is called “homeostasis,” i.e.,
a constant internal environment, while constantly ex-
changing energy, material and information with the cells’
external environment. Cells such as macrophages may be
quiescent—just minding their own business—or they may
be activated to perform a particular bodily function, such

42
 The Glycine Miracle
as inflammation. When activated, a cell changes its inter-
nal environment in response to its activation. A
macrophage, for example, when it detects—via receptor
molecules floating in its cell membrane—the presence of
chemicals coming from other cells which have been dam-
aged or killed, goes into phagocytosis (mend or M2) mode.
In this mode, it cleans up the mess of dead cells and cell
debris, so that healing—via new tissue growth—can occur.
But the macrophage can also become primed to enter the
rend (M1) mode, when it detects—again, via specific re-
ceptor molecules in its cell membrane—the presence of
components of bacteria or fungi or some other infectious
microbe. That sets into motion the construction of an in-
flammasome within the cell; the machinery for the pro-
duction and secretion of various poisons, so that the
invading microbes can be killed before they endanger the
life of the host.
Interestingly, the very switch that turns on or primes
the macrophage is actually an electrical switch, essentially
just like a wall switch that turns on the light in a room!
When the light switch is off, one pole of the switch carries
120 volts of electricity, whereas the other pole carries zero
volts. When the switch is turned on, the two poles are con-
nected by a metal (usually copper) that conducts electric-

43
 The Glycine Miracle
ity, thus bringing the voltage difference between the two
poles to zero. The electricity reaches the light bulb, and it
lights up.
In the case of a living cell, the voltage is created by the
fact that the internal environment of the cell is different
from the external environment, due to the presence of dif-
ferent concentrations of dissolved ions. Ions are chemical
entities that carry + or – electrical charges. Hence, posi-
tively charged sodium ions are present in very high con-
centration outside the cell, and low inside. But positively
charged potassium ions are the reverse: at high concentra-
tion inside the cell and low outside. Because potassium
ions are bigger than sodium ions, there is a slight differ-
ence in the overall positive charge concentration, i.e.,
slightly lower on the inside. This results—when the cell is
at rest—is an average voltage of about -0.07 volts (70 mil-
livolts) inside versus outside the cell membrane. This can
be stable because the soapy (oily) nature of the membrane
itself does not allow ions to cross, thus making it a good
electrical insulator. However, because the cell membrane
is so fluid—always in motion and exchanging various ma-
terials between the inside and outside to maintain home-
ostasis—that there is naturally some leakage that occurs.
Therefore there are special “ion pumps” that actively

44
 The Glycine Miracle
pump sodium ions out and potassium ions in, in order to
maintain the electrical and ionic balance.
There are also special pores or channels (also called
“transporters”) that allow particular ions to diffuse be-
tween the inside and outside or vice-versa, to help main-
tain that 0.07 volt “resting potential.” A critical channel
that serves this function allows negatively charged chloride
ions—which are highly concentrated outside versus inside
the cell—to diffuse in, to keep the inside negatively
charged relative to the outside. Other channels serve as
switches, actually allowing sodium and potassium ions or
positively charged calcium ions to diffuse through the
membrane, thus throwing the switch on. In fact this is
how all nerve impulses—manifesting as sensations and
muscular responses—are propagated along the membranes
of nerve cells (“neurons”). As for macrophages, the detec-
tion of the presence of invading microbes opens calcium
channels, and because calcium ions are also positively
charged, the membrane voltage goes to zero and the
macrophage becomes primed to cause inflammation. But
this also happens inappropriately if the resting potential
of 70 millivolts deteriorates enough because not enough
negatively charged chloride ions diffuse inside to maintain
it. In terms of macrophage function, the most important

45
 The Glycine Miracle
of these regulatory ion channels are what are called
“glycine-gated chloride channels,” aka “glycine receptors.”
High concentrations of the free amino acid glycine are re-
quired to keep these glycine receptors open, so that the
chloride ions can diffuse in at an adequate rate to prevent
the macrophage membrane from losing its resting poten-
tial inappropriately such as when the cell is actively per-
forming phagocytosis in response to the detection of dead
cells or cell debris. The normal extracellular concentration
of glycine is established to be about 150-350 micromolar
units because that is the average range of concentrations
that exist in the general population. The trouble is, even
350 micromolar is not high enough to prevent inflamma-
tion when there is only tissue damage but no infection.
For that stability, the concentration of free glycine outside
the cell (reflected in the blood plasma glycine concentra-
tion) needs to be over about 500 micromolar units. The
lower it is below that, the more precarious the situation,
i.e., the more the macrophages are prone to cause inflam-
mation unnecessarily.
Immunologists will argue that the above description
of the inflammation switch is a gross oversimplification.
After all, there are many different types of macrophages,
specific for different organs in which they are found, and

46
 The Glycine Miracle
in the specificity of signaling chemicals that activate them.
Thus, for example, the white blood cell macrophages
called neutrophils are particularly responsive to bacterial
infection, whereas the white blood cell macrophages called
eosinophils are more reactive to microbial parasites. Be-
yond activation, there is also a host of different cytokines
designed to more efficiently attack different microbes. In
the chronic inflammation situation wherein there is no in-
fection present, there are still different kinds of
macrophages activated, causing the various different forms
of chronic inflammatory disease. Thus, for example,
eosinophils are typically over-activated in asthma. Indeed
there are many different switches, and the most abundant
one is typically the opening of channels in the membrane
for the positively charged calcium ions—rather than
sodium ions—to come in and activate the many different
biochemical pathways needed for an inflammatory re-
sponse. But remember that it is the inappropriate or ex-
cessive activation of macrophages that is the problem in
most chronic illnesses—not the normal, appropriate acti-
vation in response to infection. What glycine does—via
the glycine receptors (glycine-gated chloride channels)—
is stabilize the cell membrane against anything that will
cause the inappropriate depolarization. Hence we recall

47
 The Glycine Miracle
the metaphor of the glycine receptor serving not as the
universal inflammation switch or trigger, but rather as the
universal “trigger lock,” preventing any or all of the diverse
triggers from being erroneously activated. Importantly,
this role provides the basis for the universality of the sta-
bilizing role of glycine vis-à-vis inflammation of any kind.

48
 Chapter Five
Red Flags
In February of 2009, while I was in the midst of both
laboratory animal research and self-experimentation on
glycine, a group of scientists at the University of Michigan
led by Arul Chinnayan (first author: Arun Sreekumar)
raised a red flag with the publication of a study on cultured
prostate cancer cells in the prominent scientific journal,
Nature. Their research claimed that the addition of sarco-
sine (a metabolite of glycine) or glycine to cell cultures of
benign human prostate cells made them turn into invasive
cancer cells. One of the unfortunate aspects of scientific
research publication is the fact that the prominence or
high “impact factor” of the particular journal is more de-
terminative of the study’s effect on medical research and
practice than the actual scientific merit of the published
study. As Nature is one of the highest impact journals in
the life sciences in the world, the Chinnayan group’s study
had a chilling effect to say the least.
Adding to the negative impact of the study were the
difficult rules by which one could attempt to refute the
findings by submitting a letter to be published subse-
quently in the journal. This particular journal required that

49
 The Glycine Miracle
a letter first be sent privately to the original authors, and
that it could only be submitted to the journal for publica-
tion following a response or lack thereof to the private let-
ter. I played by all their rules, and got no response from
the Chinnaiyan group, and the journal declined to publish
my group’s detailed letter, which included our own re-
search findings on the biochemical effects of methionine
restriction and glycine supplementation. In our letter, we
noted that their finding that adding glycine “induced in-
vasion” in benign prostate cells suggested that glycine sup-
plementation might cause or aggravate cancer. We called
this suggestion unwarranted, mainly because the so-called
“benign” cultured cells they used (RWPE cells) were actu-
ally virally transformed cells, i.e., potentially cancerous
cells in a non-invasive state. Moreover, the concentrations
of glycine to which the cells were exposed were wildly dif-
ferent from actual physiological levels in the body—only
about 10% of normal blood levels. But the real proof of
the proverbial pudding came three years later, when the
Chinnaiyan group (first author: AP Khan) published an-
other study which confirmed the carcinogenic potential
of sarcosine in experimental mice, specifically, that the
“addition of sarcosine, but not glycine or alanine, induced
invasion in RWPE cells…” Curiously they failed to men-

50
 The Glycine Miracle
tion—in their 2012 study—that the lack of effect of
glycine was contrary to their earlier result in 2009, when
they reported that glycine “induced invasion in these (be-
nign) cells.” In fact such a tumor promoting effect of
glycine would have been contrary to their findings about
sarcosine, and the authors should have said so! Hence,
their new finding of what might be called an inconvenient
truth was studiously avoided in their lengthy 2012 Discus-
sion section. Rather, they just noted that the lack of effect
of glycine was “consistent with our (their) in vitro data.”
Hence, the red flag the Chinnayan group had raised in
2009 was most inconspicuously lowered in 2012. I still get
occasional calls from customers concerned about taking
my glycine supplement, based on the 2009 false alarm.
However, just before the Chinnayan red flag was low-
ered, yet another, bigger red flag was raised in the most
prominent scientific journal Science, by a group led by
Mohit Jain of Harvard. This time, the (tacit) implication
was that glycine supplementation might cause or exacer-
bate a host of major human cancer types, including breast
cancer! The very title of the paper was full of foreboding
in terms of glycine supplementation: “Metabolite Profiling
Identifies a Key Role for Glycine in Rapid Cancer Cell

51
 The Glycine Miracle
Proliferation.” Specifically, the Jain group utilized a panel
of cultured human cancer cell lines from the collection
called the NCI-60; sixty cell lines derived from actual
human tumors of nine major cancer cell types including
breast, colon, lung, et al. These cultured cell lines had been
developed in the 1990s by the US National Cancer Insti-
tute, an organ of the US government’s Department of
Health and Human Services (HHS) and the largest entity
funding cancer research in the world. The Jain group ana-
lyzed the cultured cells’ metabolism by a method known as
metabolomics, which enables the measurement of hun-
dreds of metabolic intermediates and products simultane-
ously. It is one of a family of highly computerized methods
including such others as proteomics, genomics and
lipomics, that all measure hundreds of substances simulta-
neously. These are not really scientific disciplines in their
own right, but technological tools of science that I would
call a mixed blessing. I say this because the proliferation of
these tools has resulted in what is known as “data-based sci-
ence,” in contrast to traditional “hypothesis-based science.”
In my early days as a scientist—back in the 1970s and
80s—hypothesis-based science was pretty much all sci-
ence, as generating and testing a hypothesis is a critical
step in the scientific process. In data-based science, first

52
 The Glycine Miracle
one collects all the data possible in a given area of study—
because one can—and after computer analysis discerns
which differences between groups are statistically signifi-
cant and which are not—one then thinks up hypotheses
to try and explain the findings. Back in the 1970s and 80s,
this approach was called a “fishing expedition,” and no
agency would ever consider funding such an expedition,
because the multiplicity of things to be measured would
make such a study impossible: One needed to generate a
hypothesis first, to delineate a reasonable number of
things to measure, in order to test the hypothesis. In fact,
the investigations of both the Chinnayan group in 2009
and the Jain group in 2012 were data-based studies utilizing
metabolomics.
Hence the very idea that glycine was particularly im-
portant in cancerous tumor growth was not arrived at log-
ically, through the study of previous findings and known
characteristics of cancer cell growth; rather it just popped
out as significant from examining all the possible data. I
will have more to say about “-omics”-based research later
on in this book, but my summary view is that the “-omics”
constitute excellent and unparalleled ways to test hypothe-
ses. But to generate hypotheses; not so much.

53
 The Glycine Miracle
Getting back to the work of Jain et al., they not only
studied the established cell lines of the NCI-60, but they
also studied cells grown from actual human breast cancers,
and they were able to correlate enhanced synthesis of
glycine in the mitochondria of the tumors (compared to
normal cells) with more rapid growth and greater lethality
of the tumors. Specifically, they reported “discovering an
unexpected increased reliance on glycine metabolism in
rapidly proliferating cancer cells” compared to rapidly pro-
liferating normal cells. Hence they suggested that their re-
search might lead to breast cancer therapies that inhibit
the production of glycine by cancer cells. So even though
they did not address the topic of glycine supplementation
per se, one can see how the specter of this common nutri-
ent’s making cancers grow faster and kill faster cast a pall
over the idea of consuming more glycine!
That brings us to the question: What exactly do the
Jain group’s findings mean? After all, there is no reason to
doubt their validity, subject to the obvious limitations re-
lated to measuring the activity of cells grown in a test tube,
rather than in a living patient’s body. The first question I
ask is whether the concentrations of glycine that the cells
were subjected to are relevant to physiological concentra-
tions. Recall that normal (though not necessarily healthy)

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 The Glycine Miracle
levels of glycine in the blood plasma are between about
150 and 350 micromolar units. The Chinnayan group tested
their cells at 25-50 micromolar (about 1/10 normal) and the
Jain group used 140 micromolar (just below the bottom of
the normal range.) In both cases, therefore, the levels of
glycine that made the cancer cells grow better were below
normal levels. This does not mean their data should be dis-
carded—not at all. Rather it might be useful to test hy-
potheses concerning glycine and cancer.

55
 Chapter Six
The Evolution of Cancer
It is common knowledge that malignant tumors arise
when cells multiply out of control, after mutations
(changes in their DNA) accumulate in such a way that a
cell is transformed into a parasitic cell that escapes the
normal controls of cell division and other regulatory mech-
anisms. In the process of transformation—which may take
years—the mutated cells are subject to a Darwinian natu-
ral selection process. During this process, the mutant cells
are selected for their ability to multiply rapidly, invade nor-
mal tissues and escape the immune system’s mechanisms
for finding and destroying them. Thus, the “fittest” cells
survive to eventually form a “successful” malignant tumor,
i.e., a dangerous cancer.
A state of chronic inflammation is now understood to
provide an environment that breeds cancer. That is be-
cause lots of cellular proliferation is necessary for the heal-
ing process; for the building of new tissues to recover from
cellular death that follows any sort of injury. But in a state
of chronic inflammation, damage keeps being done, so the
proliferation of cells for the purpose of tissue repair also
becomes chronic. This chronic proliferation multiplies the

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 The Glycine Miracle
opportunities for mutations to occur (since cellular prolif-
eration requires the replication of DNA) and for abnormal
and potentially cancerous cells to arise.
Earlier, we discussed how a state of chronic inflamma-
tion will occur if glycine levels are chronically too low to
regulate the macrophages that initiate the inflammatory
process. We also saw how a diet rich in muscle meats (and
therefore rich in the essential amino acid methionine) and
poor in bones and connective tissues (and therefore poor
in the amino acid glycine) puts the body into a pro-inflam-
matory state.
Now the stage is set for abnormal, mutated cells to be
generated with increased frequency, and for the mutated
cells to be subjected to a natural selection process. Thus,
the “fittest” cells would be those that thrive in a high-me-
thionine and low-glycine environment. Both methionine
and glycine supply small pieces of the molecules—called
purines and pyrimidines—that form DNA, and the forma-
tion of lots of DNA is needed for tissue growth and tumor
growth. As noted earlier, too much methionine is treated
by the body as toxic. In fact, it is known to be toxic in that
it inhibits growth. Hence it stands to reason that a more
successful tumor cell in a high methionine/low glycine en-
vironment would be one that excels at getting rid of excess

57
 The Glycine Miracle
methionine on the one hand, and at making plenty of its
own glycine on the other. Such a cell would thrive in such
an environment.
In fact, it has been known for decades that human can-
cer cells generally are far more dependent on exogenous
methionine than are normal cells, the latter having several
ways to recycle and salvage methionine molecules. This
has even led to the development of cancer treatment
strategies that employ a methioninase enzyme that actu-
ally eliminates methionine from the bloodstream. Return-
ing to the first study that raised a red flag about
glycine—that of the Chinnaiyan group in 2009—we can
see that the principal finding of their metabolomic inves-
tigation was an accelerated activity of the one pathway
that eliminates methionine, an enzyme called GNMT, for
glycine-N-methyltransferase. That’s why they measured an
increase in the production of sarcosine, the derivative of
glycine that results from this enzymatic reaction. In the
metabolomic study of the Jain group—the second red flag
raised about glycine—the main finding was that the most
rapidly growing and lethal human cancers had a markedly
elevated capacity to make their own glycine. Thus, in ac-
tuality, these studies provided evidence in favor of the hy-
pothesis that life-threatening malignancies evolve in

58
 The Glycine Miracle
precisely the environment of elevated methionine and de-
creased glycine!
One would think that, since the reciprocal metabolic
relationship between glycine and methionine has been
documented in the peer-reviewed literature for many years
now, scientists in top institutions publishing in top journals
would be able to connect the dots. But unfortunately, the
hyperspecialization of science is a trend that has only ac-
celerated in recent years. It is as if specialists of different
species of trees do not realize they are researching the for-
est. What can one expect to learn if, when researching a
given disease process, one does not consciously relate the
findings in one experimental system to other areas of
knowledge of human physiology and biochemistry?
Another particularly relevant case in point is a study I
mentioned earlier in this book, i.e., the “data based” study
by Schmidt et al. from Oxford University, published in
2016. It was part of a very large, ongoing high profile study
in Europe (the EPIC study, which stands for The Euro-
pean Prospective Investigation into Cancer and Nutrition)
sponsored by the IARC, or International Agency for Re-
search on Cancer of the World Health Organization.
EPIC is described by the WHO as “one of the largest co-
hort studies in the world, with more than half a million

59
 The Glycine Miracle
(521 000) participants recruited across ten European coun-
tries and followed for almost 15 years.” The aim of the
Schmidt study was to correlate differences in the amino
acid content of the diets of vegans, lactovegetarians, fish-
eaters and meat-eaters (omnivores) with differences in the
amino acid content of the blood plasma of these four
groups of normal men, selected from among UK partici-
pants in the EPIC study. Thus, the researchers analyzed
the dietary intake of the 392 participants (98 in each di-
etary group) and recorded their amino acid content, and
then measured the free amino acid content of the subjects’
blood plasma.
One would think that the researchers—being on the
faculty of Oxford, a premier “world class” university, and
conducting an arm of such a prestigious multinational
study as EPIC—would expect the relationships among the
plasma amino acid content and the different dietary amino
acid intake to reflect what was known about the interac-
tions of different amino acids in human metabolism. In
particular, recall the reciprocal relationship between
glycine and methionine noted earlier in this work. Being
aware of the fact that excess methionine actually depletes
glycine, it should be expected that meat-eaters (omnivores,
that is, who normally throw the bones and connective tis-

60
 The Glycine Miracle
sues of meat, fish and poultry into the trash instead of the
soup), would have lower levels of glycine in their blood
plasma than do vegans, even though the high quantities of
protein eaten overall by the meat-eaters renders their in-
take of all the amino acids higher than that of vegans.
But that is not what the Schmidt group hypothesized,
for they are “data-based” researchers, with essentially no
hypothesis at all. Their aim was therefore simply: “to in-
vestigate the differences in plasma concentrations and in
intakes of amino acids between male meat-eaters, fish-
eaters, vegetarians and vegans in the Oxford arm of the Eu-
ropean Prospective Investigation into Cancer and
Nutrition”. Of course, their analyses of amino acid concen-
trations were correctly performed, and they found, in their
measurements of the blood plasma, “For glycine, vegans
had the highest concentration and meat-eaters the lowest.”
As part of a proper scientific investigation, the Oxford
group thus needed to discuss their findings, including re-
viewing the relevant literature, to determine the clinical
relevance of their statistically significant findings, espe-
cially those they found surprising. But in their discussion
of results, they invoked the common generalization about
“complexity,” i.e. “The plasma concentration of amino
acids is a result of a complex interplay between dietary in-

61
 The Glycine Miracle
take, (and) tissue breakdown,” and simply reported that
among the four different dietary intake groups, there were
significant differences in the concentrations of six amino
acids, and “The largest percentage difference between
meat-eaters and vegans in plasma concentration was found
for glycine (16%), for which vegans had the highest concen-
tration.” All they offered to “in part explain” this was that
soybeans—which the vegans ate more of—have lots of
glycine, and how higher glycine has been reported to be as-
sociated with a lower risk of diabetes. (This was a 2013 find-
ing from another group in Germany, which was also part of
the EPIC study team.) But they offered no potential expla-
nation as to why the meat-eaters had the lowest plasma
glycine of all, even though they ate the most glycine.
Hence, as disappointing as it was that these presum-
ably erudite authors did not expect to find the big differ-
ences between vegans and meat-eaters in terms of
methionine and glycine, it was more disappointing to read
that they were unable or unwilling to do the basic library
research that would have revealed to them the knowledge
of the glycine-methionine connection, even after they ob-
tained their surprising results.

62
 Chapter Seven
The State of Life Science Research
These days, one is all too familiar—especially in relation
to public health and the COVID pandemic—with the ral-
lying cry “Follow the science!” And within scientific circles,
the familiar rallying cry is: “Show me the data!” But as we
have just seen in the preceding chapter, the data is not of
much use without proper interpretation. Do the data con-
firm or at least support the underlying hypothesis, or per-
haps disprove or mitigate against it? In the absence of a
hypothesis, the data can easily be simplistically interpreted
to lead one in exactly the wrong direction. Thus, the fact
that the most aggressive human cancers make and utilize
more glycine has been misinterpreted to mean that glycine
supplementation is bad for you, and might cause cancer or
make cancer worse. Yet we see that when these findings are
interpreted in the broader context of tumor evolution, it
makes perfect sense that successful tumors will have to
make more glycine than normal cells, if they arise in an en-
vironment where glycine is below a healthy level.
If we are therefore to follow the science, it needs to be
real science; that is to say whole science: embodying the
whole of the scientific method, rather than being just

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 The Glycine Miracle
about the data. Hence it is worth considering here just
what constitutes the scientific method.
The very word “science” is derived from the Latin verb
“scire,” meaning “to know.” Hence the scientific method
is a method for acquiring knowledge about some phenom-
enon. In particular, science aims to discover the natural
law which governs the phenomenon in question, in other
words, the ”Why?” Thus, the scientific quest always begins
with a question. When the mind entertains a question, an
answer will usually come to mind, based on previous ob-
servations and experiences. That answer would be the hy-
pothesis. But it is, as it were, only a hypothetical answer,
because it needs to be tested in the phenomenal (physical)
world. Hence the mind is presented with a second ques-
tion, i.e., how can the hypothesis be tested? In the scien-
tific process, any hypothesis that cannot be tested must
be rejected. So the mind seeks a model system—some sort
of controlled experiment or set of observations in the phe-
nomenal world; a metaphor for the phenomenon under
study—to test the hypothesis. Then comes the actual con-
ducting of the experiment: This is where most of the
money is spent, and where the data are generated. If the
experiment was designed and conducted properly to an-
swer the original question, the results—the experimental

64
 The Glycine Miracle
data—should reveal whether the original hypothesis was
correct, in whole or in part.
But these days, it’s all about the data. And as we have
just seen, the same dataset can be interpreted in different
ways, and not necessarily correct ones. It has therefore be-
come more and more difficult to sort through the astro-
nomical expansion of life science research data in search
of what is correct and important and relevant to answering
questions about human health and disease. One scientific
principle, the application of which is often forgotten, is
typically referred to as “Ockham’s Razor.” This principle,
attributed to the 14th Century theologian William of Ock-
ham, is commonly expressed as a preference for the sim-
plest possible hypothesis that can answer a given question.
A familiar historical example would be the Ptolemaic hy-
pothesis that the sun revolves around the earth, as do the
planets, in complex gyrations called “epicycles.” In stark
contrast is the now accepted Kepler model that has the
earth and other planets revolving around the sun in simple
elliptical orbits.
Yet curiously, findings from disparate areas of study
that point to a simple common factor tend to be met with
more, rather than less skepticism. The seminal 1999 review
by Wheeler et al of the Thurman group in 1999 illustrates
this tendency:
65
 The Glycine Miracle
“For many, it is difficult to fathom that beneficial ef-
fects can be obtained in several disease states with the sim-
plest amino acid, glycine. However, evidence continues to
mount in favor of this idea.”
No, when disparate findings appear to be connected to
a single factor or substance, the problem is actually more
easy to fathom, not difficult to fathom! That is the mes-
sage of Ockham’s Razor. One does not reject a hypothesis
because it is too simple; rather, because it is too compli-
cated! Yet these days, as I noted earlier, the claim that the
problem is complex is often a cover for a lack of knowl-
edge, a hedge to hide behind while maintaining a façade
of wisdom and expertise.
But, adding to the tendency to believe that the causes
of all manner of dysfunction in complex systems that com-
prise human physiology must themselves be complex in-
stead of simple, is the tendency to think of anything that
normalizes abnormal function to be some kind of drug.
Even the recent (2021) review article (from a group headed
by Zhending Gan of the South China Agricultural Univer-
sity in Guangzhou) that catalogs the benefits of glycine
supplementation in diseases rooted in inflammation,
speaks of “the potential application of glycine supplemen-
tation as an adjuvant therapy in macrophage-associated

66
 The Glycine Miracle
diseases.” Don’t you see? Glycine may be a terrific drug!
But just think: these days, no one would ever consider the
B vitamin thiamine to be a drug that cures the disease pel-
lagra, nor vitamin C to be a drug that cures the disease
scurvy, so why would a single substance that stops inap-
propriate or excessive inflammation be considered a drug?
An important part of the answer to that question is
rooted in the belief that glycine is generally considered
“non-essential.” So why would anyone place too much cre-
dence on the importance of a nutrient we know to be non-
essential? In another context, it is interesting to note that,
during the recent pandemic of COVID 19, many state gov-
ernments in the US closed many businesses which were
deemed to be “non-essential.” Hence many hard-working
citizens learned the hard way that their livelihood—cer-
tainly essential to their own families’ well-being—could be
thought of as “non-essential!” So we might say that the
word “non-essential” itself is toxic: destroying livelihoods
in the workaday world, and throwing scientific research
off the trail of finding the root cause of so many illnesses
that destroy lives. I have become convinced that these dis-
eases should be thought of as glycine deficiency diseases.

67
 Chapter Eight
Anti-Inflammatory
With the recent realization that inflammation lies at
the core of so many modern-day ailments, the term “anti-
inflammatory” has become something of a buzzword. Peo-
ple search for foods and supplements and drugs that are
“anti-inflammatory” as things that might improve health.
That makes perfect sense, and I’m happy to promote the
use of supplemental glycine as anti-inflammatory and ben-
eficial, as glycine is the ultimate anti-inflammatory nutri-
ent. But the term “anti-inflammatory” covers quite a bit of
territory. There are, for example, supplements marketed to
“fight inflammation.” This is because these substances ac-
tually suppress, in some way, some stage or stages in the
multi-stage inflammatory cascade. So for example, the
commonly used non-steroidal anti-inflammatory drugs
(“NSAIDs, e.g. ibuprofen and acetaminophen) suppress the
generation of chemical signals (called prostaglandins) that
recruit additional macrophages to the site of inflammation.
More recent types of drugs called “biologics” are actu-
ally semi-synthetic antibodies to specific chemical poisons
that form part of the inflammatory response. These are
used to treat conditions that produce symptoms that are

68
 The Glycine Miracle
traceable to specific of these inflammatory components.
Perhaps the most well known example is adalimumab (the
most common brand is Humira®), which has been around
for over 20 years. The last three letters “mab” stand for
monoclonal antibody. Unlike natural antibodies, “mabs”
are products of genetic engineering such that these anti-
bodies do not generate antibodies in the patient that
would cause a rejection reaction of some sort. That makes
them safe to use on one level, but fundamentally, these
“mabs” are dangerous precisely because they are designed
to disable a natural function of the immune system.
Adalimumab, for example, specifically inactivates the
cytokine called “tumor necrosis factor alpha” (TNFα).
Adalimumab is used to treat a variety of chronic inflam-
matory conditions, including rheumatoid arthritis, anky-
losing spondylitis, Crohn’s disease, et al. It works because
TNFα is near the top of the inflammatory cascade; a prod-
uct of M1 activated macrophages that can generate fever
and induce cell death and all manner of damage typical of
inflammation. This makes TNFα an important compo-
nent of the inflammatory response to infectious disease.
That’s why, in all the advertising for all the mabs, there is
a whole list of warnings about the development of serious,
potentially life-threatening infections with use of the mab.

69
 The Glycine Miracle
Since they are proteins (All antibodies are large protein
molecules), these medications are only available as injecta-
bles, because the protein structure would be broken down
by the digestive system if taken orally. These medications
are also chemically modified to be released into the circu-
lation slowly over time, so dosing needs to be repeated
after some weeks or months. Of course, all these drugs do
not act to cure any of these inflammatory diseases, pre-
cisely because they fight inflammation, rather than natu-
rally regulating it, as adequate glycine does. But remember
that glycine—which is not a drug of any kind—only sets
the threshold for macrophage activation higher (i.e., to a
truly healthy level), so that inflammation can still take
place when it is appropriate, i.e., in the presence of an ac-
tual microbial infection.
Still, one would think that long term use of an anti-in-
flammatory medication would lessen the inflammatory
damage over time, so that there should be an improve-
ment, provided the absence of natural inflammation did
not result in serious infectious disease. That’s why Johanna
Luitjens and colleagues at the University of California at
San Francisco (UCSF) studying the long-term effects of
NSAIDS on osteoarthritis in the knee, found their own
results to be counterintuitive. They reported their findings

70
 The Glycine Miracle
at the Annual Meeting of the Radiological Society of
North America in 2022. Contrary to their expectations,
MRIs of the knees of patients who used these NSAIDS
(ibuprofen or acetaminophen) actually evidenced more de-
generative changes in their knees than those who did not
take NSAIDS. Why? It does seem paradoxical, but in ac-
tuality the answer is quite simple. The issue is rooted in
imprecise language. Although the NSAIDS act, in part, as
anti-inflammatory agents by blunting the recruitment of
inflammatory cells (part of a group of drugs known as cy-
clooxygenase or COX inhibitors), their main immediate
pharmacological action is that of an analgesic. Analgesics
act by directly reducing pain signals to nerve cells. That’s
why these drugs are so popular: They reduce pain pro-
duced by the movement of a joint which is also suffering
inflammation. And although inflammation produces pain,
the typical pain of motion in osteoarthritis is not the di-
rect result of inflammation, rather the result of moving a
damaged member and directly irritating pain-sensitive
nerve endings.
In other words, people take NSAIDS in order to be able
to work through the pain by reducing the pain. Therefore,
remaining active with joints already damaged by chronic in-
flammation will cause further damage to the joints, neutral-

71
 The Glycine Miracle
izing or even exceeding the anti-inflammatory benefits of
NSAIDS. That is only surprising because we call drugs
which are primarily analgesics, anti-inflammatories.
Here, then, is another example of confusion and misdi-
rection resulting from using the wrong word to describe some-
thing, rather like calling glycine a “non-essential” nutrient.

72
 Chapter Nine
Back to the Science, a
Global Hypothesis Regarding
Glycine and Inflammation

The Hypothesis
Whereas most chronic diseases are traceable to some
form and degree of chronic inflammation, and other con-
ditions or diseases are traceable to acute inflammation in
the absence of any benefit of inflammation, and whereas
glycine stabilizes macrophages from inappropriate or ex-
cessive priming by permitting adequate influx of chloride
ions through glycine-gated chloride channels (aka glycine
receptors) on the macrophage cell surface, it is hypothe-
sized that all such disease conditions, whether acute or
chronic, result from a deficiency of glycine in the blood
plasma and may therefore properly be referred to as glycine
deficiency diseases or glycine deficiency conditions.
If this hypothesis is correct, we should expect to make
the following observations:

1. The supplementation with glycine of diets of those

suffering from any of these conditions will cause a rise in

73
 The Glycine Miracle
plasma glycine concentrations and symptomatic improve-
ments in all these conditions.
2. People suffering from any of these diseases or con-
ditions will have plasma glycine concentrations lower than
those of unaffected controls.
3. A clear mechanism for the causation of these condi-
tions should be demonstrable, i.e., what caused the stim-
ulus for activation of macrophages that caused the
condition, which activation would be putatively prevented
by raising plasma glycine concentrations above the thresh-
old needed to prevent such activation. This would include
any condition in which the macrophages would be pre-
sented with the results of tissue injury, i.e., dead and dying
cells and/or cellular debris. An obvious example would be
blunt injury, where tissue damage clearly occurs. Less obvi-
ous are recurring physiological situations in which cell death
normally occurs, such as ovulation in the ovaries, or pre-
menstrual regression of breast tissue during each non-con-
ceptive monthly cycle and during weaning. The same is true
for some normal developmental programs, such as in the
brain, where embryonic or early childhood brain tissue is
resorbed as the adult brain is being formed. These condi-
tions will be examined in some detail later on in this book.

74
 The Glycine Miracle
4. Glycine deficiency diseases or conditions should be
more common among people who consume less glycine
and/or more foods which deplete plasma glycine.
5. Since all these chronic putative glycine deficiency
conditions have become more common in recent decades,
dietary habits in the population at large should be known
to have shifted, in recent decades, toward less glycine in-
take and/or greater intake of methionine-rich foods, such
that plasma glycine levels in the population at large have
decreased over the last few decades.

The Proof
These days, proof from an actual clinical trial must be
produced in order to establish the role of any substance in
normal or abnormal physiology—in other words, almost
that of a controlled experiment is required. The best type
of clinical trial—one that approaches the design of a real
controlled experiment—is a placebo-controlled, random-
ized clinical trial, and the bigger the better, as the results
become more statistically reliable as the numbers increase.
Yet, while it is generally true that a placebo-controlled ran-
domized clinical produces more reliable results than stud-
ies in which many factors cannot be controlled, convincing
proof of anything can be provided by other means.

75
 The Glycine Miracle
For example, the weakest sort of study is a correla-
tional study. In a correlational study, a population of ob-
served subjects with and without a given disease is
compared to, say, the overall exposure to the putative
causative agent in the general population. In such a study,
one is not even comparing, on an individual basis, those
with versus those without the exposure in question that
developed or did not develop the disease in question.
Nevertheless, in the early 2000s, a study of the corre-
lation between the sudden drop in breast cancer incidence
in the general population of US women over 50 years of
age, and the sudden drop in combination hormone re-
placement therapy (HRT) use in postmenopausal US
women, was taken to be decisive. That is, it was taken as
legitimate proof that combination HRT is a causative
agent in breast cancer. Importantly, the known cellular
proliferation-inducing effect of these drugs had also been
established, so that a likely mechanism for the cancer-caus-
ing effect was present. It was in fact a placebo-controlled,
randomized clinical trial of combination HRT as a puta-
tive preventative for heart disease—called the Women’s
Health Initiative or WHI trial—that led to the sudden
drop in combination HRT use. Specifically, interim results
after 2.5 years of the five-year study showed an increase—

76
 The Glycine Miracle
rather than the expected decrease—in heart attacks, forc-
ing the early termination of the WHI study. The attendant
publicity included the fact that breast cancer incidence
was also increased among WHI study participants, which
resulted in a 70% decrease in combination HRT prescrip-
tions the following year. The findings of the WHI study
have been recently reviewed by Petra Stute of the Univer-
sity of Bern, Switzerland.
In the case of the present hypothesis concerning
glycine, there is a wealth of study data from a multiplicity
of types of studies, all of which point in the direction of
confirmation of the hypothesis. Clinical trial data, how-
ever, are rare. In the remainder of this chapter, we’ll exam-
ine the evidence that fulfills the first two elements of proof
listed above.

1. Glycine supplementation showing improve-

ment in an inflammation-based condition:

One clinical trial by Cruz et al.—apparently a one-
off—was published in 2008. It was in fact a randomized,
placebo controlled trial of oral glycine, 15 grams per day,
in type 2 diabetic patients in Mexico City. Although the
study was small by clinical trial standards—74 patients—
there was a significant reduction in the premier blood test

77
 The Glycine Miracle
marker for type two diabetes: Hemoglobin A1c, which was
reduced, on average in the glycine-treated group, from 8.3
to 6.9. This is quite a dramatic result, all the more remark-
able because the patients were consuming their normal
anti-diabetic medications all along. (It would not be an
ethical study otherwise.)

In their discussion of results, Cruz et al. focused on the

results that showed a decrease in inflammatory markers in
the blood with glycine treatment, and cited research from
the early 2000s which linked type 2 diabetes to inflamma-
tion. Unfortunately, the authors did not highlight the dra-
matic reduction in Hemoglobin A1c they also observed.
Were it up to me, I would have entitled the paper:
“Glycine supplementation reverses type 2 diabetes.” More-
over, the study was not published in one of the top “high
impact” endocrinology journals, and it remains in relative
obscurity to this day.

The Cruz study is one of the very few clinical trials to

date to focus on any anti-inflammatory effects of glycine
supplementation. (There have been other trials of glycine
supplementation in psychological disorders, based on
glycine’s action as an inhibitory neurotransmitter in the
brain, and without striking results.)
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 The Glycine Miracle
2. Comparison of blood glycine levels in subjects

with versus without an inflammation-based

condition:
This is an area in which metabolomics—data-based
science—is most useful. In terms of clinical studies, it is
the easiest kind to perform. Often, there are blood sam-
ples that have already been collected from many—some-
times tens of thousands—of patients, and literally
hundreds of metabolites may be measured in a single pass
from a very small amount of stored plasma or serum.

With respect to type 2 diabetes, if it is indeed a disease

of glycine deficiency, differences in glycine concentration
should be demonstrable in matched groups of subjects
with versus without type 2 diabetes in a metabolomic
analysis. Indeed, the high and increasing prevalence of this
condition has focused a great deal of research attention on
it. Exemplifying this trend, Harvard nutritional scientist
Marta Guasch-Ferré and coworkers published a systematic
review and meta-analysis (SRMA) in 2016, which pooled
results from 46 separate studies where metabolomics had
been used to measure a wide spectrum of metabolites, in-
cluding all the amino acids. Only two of the amino acids—

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 The Glycine Miracle
glycine and glutamine—were found to be at significantly
lower concentrations in the blood of pre-diabetics (a con-
dition typically preceding onset of type 2 diabetes and
characterized by insulin resistance) and type 2 diabetics.
This study of studies—comprising thousands of patients—
does not prove the glycine hypothesis in terms of causa-
tion of diabetes, but failure to find this result—an inverse
association between glycine and diabetes or prediabetes—
would essentially disprove the glycine hypothesis. After
all, how could you view diabetes as a glycine deficiency dis-
ease if there is no difference between blood glycine con-
centrations among diabetics versus nondiabetics? Finding
that glycine levels are lower in diabetics and pre diabetics
than in a healthy, matched population therefore provides
essential—though not sufficient—support for the glycine
hypothesis.

The Guasch-Ferré study is important, although it suf-

fers from its being a metabolomics study. That is, as a data-
based study, it does not begin with a hypothesis
concerning why one might expect particular metabolites
to be increased or decreased in diabetics. Rather it is in-
deed a fishing expedition. The findings of significantly de-
creased plasma glycine and glutamine were significant

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 The Glycine Miracle
“fish” that were caught. But what did it mean? This was
explored in a very cursory fashion in the Discussion sec-
tion of the paper. No specific hypothesis was offered;
rather just the citation of a 2002 study showing generic ef-
fects of amino acids on glucose metabolism. To the data-
based scientist, hypothesis comes as an
afterthought—with most of the paper devoted to statisti-
cal analysis of data.

Remember that the Guasch-Ferré study was published

four years after the publication of the Cruz clinical trial of
glycine for type 2 diabetics, and both the significant re-
duction of Hemoglobin A1C and of markers of inflamma-
tion were among the positive effects of supplemental
dietary glycine that the Cruz study documented, and the
anti-inflammatory effects of glycine were demonstrated
almost 20 years after the pioneering work of the Thurman
group. One might expect, therefore, that Guasch-Ferré et
al. might have connected the proverbial dots: diabetes, in-
flammation and glycine. Then again, a look at the stated
objective of the Guasch-Ferré paper reveals the self-im-
posed limitations on the group’s efforts:

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 The Glycine Miracle
OBJECTIVE
To conduct a systematic review of cross-sectional
and prospective human studies evaluating metabolite
markers identified using high-throughput metabolomics
techniques on prediabetes and type 2 diabetes.”

Where is the objective to further understand diabetes,

what causes it, how to predict it and cure it? These objec-
tives may seem implicit merely by virtue of the fact that
the study was funded by the NIH and the American Dia-
betes Association. Instead, the fixation on the data ob-
scured the importance of the group’s own findings!
I should also mention the connection that the Guasch-
Ferré group found with the amino acid glutamine being
reduced among diabetics and pre-diabetics. The likely rea-
son is straightforward. Unlike most amino acids, which are
made by the liver, the amino acid glutamine is mainly made
by muscle. Insulin resistance manifests mainly as a de-
creased ability of muscle to take up the fuel glucose from
the circulation, thus muscle function is inhibited, and a
decrease in glutamine production is to be expected. There-
fore, we may infer from the Guasch-Ferré group’s findings
that the decrease in glycine reflects the cause of insulin re-
sistance, and the decrease in glutamine reflects the effect

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 The Glycine Miracle
of insulin resistance. (As we shall see later on, the synthesis
of glycine is also affected by insulin resistance and dia-
betes. Hence, low glycine may indicate both cause and ef-
fect.) Speaking of other amino acids, another study by a
group at Baylor College in Houston, Texas, published in
2011—a clinical trial, actually—showed similar benefits in
type 2 diabetes after supplementation with glycine in com-
bination with another amino acid: cysteine. More on that
study in a later chapter.
Data-based metabolomic studies have also linked
blood glycine levels to other serious chronic diseases
linked to inflammation, such as cardiovascular disease. As
the glycine hypothesis would predict, such studies also
show decreased blood levels of glycine linked to adverse
cardiovascular events, mainly heart attacks and strokes.
In 2015 Hartiala and colleagues at the Cleveland clinic
used metabolomics to identify genetic variations for genes
that code for enzymes involved in the synthesis and me-
tabolism of glycine, as some of these had been identified
with reductions in heart disease risk. They discovered a
highly significant connection between defective glycine
clearance and a 12% lower risk of coronary artery disease
(CAD) in women. While this did not prove that the ele-
vated blood glycine levels were responsible for the lower

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 The Glycine Miracle
risk of CAD, the authors cited earlier (2012) research that
had shown the inflammation reducing and “cardioprotec-
tive” effects of glycine. Importantly, they also showed that
the significant risk reduction in the genetic variant popu-
lation disappeared when they statistically adjusted for the
increased glycine. This is good statistical evidence that the
increased glycine levels in the variant population were re-
sponsible for the decrease in CAD risk.
The following year (2016), Yupeng Ding and colleagues
at the University of Bergen, Norway, and the University of
Florida, looked specifically for a protective effect of
glycine for CAD (real hypothesis-based science!). They in-
cluded over 4,000 participants in their study of male and
female patients with suspected stable angina, which is es-
sentially, quiescent CAD. The researchers followed up the
participants for an average of over seven years, and com-
pared blood glycine levels of those who had an acute my-
ocardial infarction (AMI, i.e., a heart attack) with those
who did not. What they found was about the same risk re-
duction for AMI (11%, and statistically significant) as the
Cleveland clinic had found the prior year for CAD.
Another, more recent observational study on obese
teenagers adds support to the importance of glycine defi-
ciency as a cause of cardiovascular disease (CVD). Wagner

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 The Glycine Miracle
Luiz do Prado of the California State University and col-
leagues at children’s health centers in Jacksonville, Florida,
Wilmington, Delaware and the Mayo Clinic in Rochester,
Minnesota, studied patients aged 14-18 years, to follow up
on the growing body of research linking CVD to low levels
of glycine. Specifically, since CVD occurs almost exclu-
sively in older adults, they hypothesized that the inverse
correlations between glycine and obesity, prediabetes and
markers of inflammation (C-reactive protein or CRP, and
Interleukin 6 or IL-6) seen in adults, would also show up
in children. They also noted that recent studies had shown
a distinct decrease in blood glycine levels among obese
children and adolescents. Confirming their hypothesis
about parallels between CVD biomarkers in children and
adults, the authors concluded: “Given that CVD progres-
sion is a continuum and the disease itself is not present in
children and biomarkers are typically used to monitor
CVD in children, the links between GLY and biomarkers
of CVD provide evidence for the first time of a potential
role for GLY in CVD in children with obesity.”
Finally, regarding the work of do Prado and colleagues,
it is noteworthy that they are among only a handful of re-
searchers who consider glycine not “non-essential,” but

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 The Glycine Miracle
rather as a “conditionally essential” amino acid. In my view,
that in itself represents major progress!
We will take a closer look at obesity and its conse-
quences vis-à-vis glycine in the next chapter.

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 Chapter Ten

How Does Glycine Deficiency Result

in Specific Disease States?
As we have seen, glycine deficiency results in excess or
inappropriate inflammation when there is tissue damage
(i.e., cell death). Harking back to Chapter Nine and the
glycine deficiency hypothesis I have advanced, any disease
state that is rooted in chronic inflammation should be
shown to have, as a chronic condition that leads to disease,
a chronic situation of cell death in a particular tissue or
organ. Here we will discuss in some detail the connection
between chronic cell death and the ultimate development
of a serious disease state, in most of the diseases that make
people sick and die these days.
The types of situations involving cell death can be di-
vided into 4 types:

1. Normal development of certain organs and tissues

2. Certain physiologically cyclical processes.
3. Trauma from any sort of injury, or ‘micro injuries’
due to normal internal or external physical activity
or reinjury from disturbance of scar tissue from

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 The Glycine Miracle
previously healed traumatic injury.
4. Direct harm to normal cells by infectious mi-
crobes (to which some level of inflammation is an
appropriate response, but overreaction to which
produces more serious or chronic disease).
5. In addition to all these conditions producing some
level of excess inflammation when glycine is defi-
cient, inflammation may be provoked for un-
known reasons, such as in migraine headaches.

1. Developmental Processes: Autism (most com-

monly now referred to as Autism Spectrum Disorder or
ASD)—a serious condition which starts before birth. The
development of the human brain—both before and after
birth, until about age 25—occurs via the multiplication of
precursor cells into solid masses of cells, followed by the
elimination of cells that are not needed. These unneces-
sary cells are eliminated by cells called microglia—the
macrophages of the brain—doing their normal phagocy-
tosis of cells which die. But if glycine is deficient, the death
of the unnecessary neuron precursor cells primes the mi-
croglia to cause inflammation. In 2011, PH Patterson ob-
served “an ongoing, hyperresponsive inflammatory-like
state in many young as well as adult autism subjects.” Using

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 The Glycine Miracle
postmortem brain specimens from ASD v normal subjects,
Lee et al observed “a shift in microglial phenotype that
may indicate impaired synaptic plasticity and a chronic
vulnerability to exaggerated immune responses.” More
specifically, they described “a significant increase in
primed microglia (i.e., M1 v M2 phenotype) in gray matter
of ASD compared to typically developing individuals.” Al-
though Patterson did not measure nor implicate glycine
deficiency, Wheeler, et al. of the Thurman group at UNC
had elucidated the role of glycine in macrophage activa-
tion back in the 1990s. Moreover, in 2017, Mori et al
demonstrated experimentally the ability of glycine to ame-
liorate brain damage in rats. My own summary analysis of
autism as a glycine deficiency condition was published as
an e-letter on the British Medical Journal’s website in 2018.

2. Physiological cyclical processes: Menstrual cycle

a) Ovulation and ovarian cancer: While ovulation

is the normal process of the ejection of a mature egg (sec-
ondary oocyte) from alternate ovaries during a woman’s
fertile years, it is a rather violent process, causing injury to
the surface of the ovary. Over a half century ago, in 1971,
MF Fathalla at Assiut University in Egypt observed the
epidemiological (statistical) association between number

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 The Glycine Miracle
of lifetime ovulations and the frequency of ovarian epithe-
lial cancer (the most common type of ovarian cancer in
women). He noted that most ovulations in modern times
served no purpose, and that the repeated trauma to the
ovarian surface somehow promoted the development of
cancer. Ovulation, after all, is naturally stopped when a
woman is pregnant or breastfeeding, and these situations
had become rare by the late 20th century. Artificially, birth
control pills (which are generally composed of synthetic
estrogen and progestin drugs) generally act via suppression
of ovulation, and their use is also known to be associated
with a decreased risk of ovarian cancer. However, for al-
most 30 years the dominant theories as to the cause of
ovarian cancer centered on hormones, especially estrogen,
but no conclusive connections were found. Finally, in 1999,
RB Ness and C Cottreau at the University of Pittsburgh,
suggested that “inflammation is a pathophysiologic con-
tributor to the development of ovarian cancer,” due to the
effects of inflammation causing “cell damage, oxidative
stress, and elevations of cytokines and prostaglandins, all
of which may be mutagenic,” i.e., can cause mutations in
the cellular DNA. Meanwhile, any suggestion as to a con-
nection between ovarian cancer and glycine status has yet
to appear in the medical literature, to my knowledge.

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 The Glycine Miracle
b) Breast Cancer. Most people think of a woman’s
menstrual cycle as a process that happens in the ovaries
and the uterus. However, the cyclical hormonal changes—
which occur in the ovaries—have effects body-wide, in-
cluding the breasts. Many women experience breast
tenderness in the third week of the menstrual cycle, be-
cause the combination of estrogen and progesterone that
peak during that time cause a growth spurt in the breasts.
That is, they cause a burst in cellular reproduction to begin
the massive breast growth that will be needed if concep-
tion occurs and a baby develops who will need to be fed
after birth by the breasts. However, if conception does not
occur, all those extra cells that were created need to die
off and their substance resorbed, a perfectly normal re-
gression process that happens before menstruation. But if
glycine is deficient, this regression process is characterized
by a low-grade inflammation. In terms of epidemiology,
the science that statistically relates specific exposures to
specific outcomes, breast cancer risk is proportional to the
lifetime number of menstrual cycles. However, the use of
birth control pills is known to increase the risk of breast
cancer, in contrast to decreasing the risk of ovarian cancer.
That is attributable to the fact that the combination of es-
trogen and progestin drugs in birth control pills, stimulate

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 The Glycine Miracle
cellular reproduction in the breasts for most of the
monthly cycle, rather than the normal estrogen-proges-
terone-mediated growth stimulus that happens only for
several days (during what is called the luteal phase) of a
normal menstrual cycle. Hence, with more growth in the
breasts each month, there is more cell death (tissue resorp-
tion), and, if glycine is deficient, more inflammation hap-
pening each month.
In addition to the monthly cycle of growth and regres-
sion that occurs during non-conceptive menstrual cycles,
The growth of breast tissue is much more massive if con-
ception occurs. Then, the hormonally driven growth spurt
that happens during the luteal phase of the cycle acceler-
ates with exponential increases in the same hormones
(estradiol, the main form of estrogen, and progesterone)
secreted by the ovaries and later, by the placenta. That is
why the breasts typically double in size during a normal
pregnancy. If the hormonal support for this massive
growth is suddenly stopped by an abortion of the preg-
nancy, the resulting inflammation (if glycine is deficient)
shows up epidemiologically as an increased risk for breast
cancer among women who have had any induced abor-
tions. (I have published, along with several colleagues, sys-
tematic reviews and meta-analyses of the research on this

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 The Glycine Miracle
subject in 1996 and 2018.) If, however, the pregnancy con-
tinues to term, breast cancer risk is known to decrease,
compared to no pregnancy at all. This protective effect of
full-term pregnancy was first established in 1970 by a land-
mark World Health Organization (WHO) study led by
Brian MacMahon at Harvard. The protective effect is at-
tributable to the differentiation or maturation of the ex-
cess breast tissue generated by the pregnancy, into mature
tissue capable of producing milk. The terminally differen-
tiated cells of these breasts, being no longer capable of cel-
lular division, thus produce no mutations in their DNA
from cellular division, and therefore do not give rise to ma-
lignancies. However, there is a measurable increase in
breast cancer risk after birth, if the infant is not breast fed,
or after weaning if the infant is breastfed. That’s because
the massive regression of the excess breast tissue produces
substantial inflammation, if glycine is deficient. Finally, it
should be noted that miscarriage (aka spontaneous abor-
tion) does not produce an increase in breast cancer risk.
That is because most miscarriages occur when the embryo
or fetus dies too early during the pregnancy for the preg-
nancy to have generated a massive growth spurt.

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 The Glycine Miracle
3. Microinjuries from normal physical or physio-

logical activity

a) Blood circulation and cardiovascular disease.

The arterial part of the circulatory system constitutes a
high-pressure fluid distribution system. As such, there is
naturally some level of turbulence, which is maximal
around high-pressure branch points. The most turbulence
is therefore to be found where the pressure is greatest,
where the coronary arteries (which serve the heart muscle
itself) branch off the ascending aorta, the carotid arteries
(which serve the brain) branch off the brachiocephalic ar-
tery, and the renal arteries (which serve the kidneys)
branch off the descending abdominal aorta. Not surpris-
ingly then, the major—often life-threatening—adverse
events in cardiovascular disease involve blockages that
occur at these branch points, i.e., heart attacks, strokes
and kidney failure, respectively. It has long been recog-
nized that these events follow years of buildup of athero-
sclerotic plaques from a chronic inflammatory process,
which progressively occlude the arterial opening. Finally,
the adverse event often occurs when a blood clot inappro-
priately forms at this narrowed point, thus abruptly stop-
ping the blood flow at that point altogether. More recent

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 The Glycine Miracle
research has begun to tie adverse cardiovascular outcomes
with lower levels of blood glycine (as we saw in the previ-
ous chapter) with the work of Hartiala and Ding in 2015
and 2016, respectively. Hopefully, researchers will increase
their focus on glycine. It should be noted that even the ob-
servation of an inverse correlation between adverse car-
diovascular events and blood glycine is still restricted to
the “normal” range of glycine concentrations, which is re-
ally quite sub-optimal. Hence, observed differences in out-
comes and glycine levels, while statistically significant, will
hardly be as dramatic as one would expect between those
with healthy high glycine levels and the general public.
This sort of conclusive finding would be expected only in
a long-term clinical trial of those with v without glycine
supplementation.

To this point I would also hypothesize that glycine sup-

plementation might also serve to dramatically reduce the
risk of adverse cardiovascular events due to the inappro-
priate formation of blood clots (i.e., heart attacks and
strokes) among those with existing extensive cardiovascular
disease, i.e, substantial occlusion of critical arteries. That
is because glycine acts in three important ways to reduce
the risk of inappropriate clot formation, as there are essen-

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 The Glycine Miracle
tially two interdependent systems to form clots in the
bloodstream: 1)The formation of clumps of platelets (aka
thrombocytes, which literally means “clot cells”), and 2) the
chemical formation of glycoprotein nanofibers (called fib-
rin), which turn the liquid blood plasma into a gel.
Normalization of platelet aggregation: In 2013
Peter Schemmer and coworkers of the Thurman group at
UNC established the presence of glycine receptors in rat
and human platelets, and showed that glycine reduced
platelet aggregation (clot formation) in a dose-dependent
manner. That means, the more glycine, the less likely were
the platelets to stick together. Importantly, the platelets
could still aggregate normally—as in response to an actual
cut in the blood vessel wall—with concentrations of
glycine 2 or 3 times higher than the “normal” (but actually
suboptimal) levels.

Normalization of chemical clot formation:

When there is damage to the blood vessel wall, the cells
of the wall’s lining (called the endothelium) release a pro-
tein called “tissue factor” which begins a chemical cascade
(the coagulation cascade) that amplifies the reaction and
which culminates in the formation of a fibrin clot. That is,
the last step in the cascade is the conversion (via the acti-

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 The Glycine Miracle
vated enzyme called thrombin) of the soluble glycoprotein
called fibrinogen into an insoluble matrix; a nano-mesh-
work, as it were, that turns the liquid blood plasma into a
gel. Of course, such a biochemical system that turns a very
small injury into a sizable clot capable of plugging the hole
in the blood vessel, must be very tightly controlled, lest
the whole circulatory system form one big clot, which
would be rapidly fatal! Therefore, the clotting system is
designed such that, when the coagulation system is acti-
vated, another cascade (the fibrinolytic cascade) is simul-
taneously activated. The fibrinolytic cascade culminates in
the enzymatic digestion of the fibrin (via the activated en-
zyme called plasmin), thus dissolving the clot. However, in
the location of the actual injury site through which blood
is flowing out of the vessel, another enzyme called factor
XIII or fibrin stabilizing factor, chemically cross-links the
nanofibers of fibrin, so that the plasmin cannot dissolve
the plug that fills the hole.

The two ways in which glycine stabilizes the chemical

coagulation system are through normalizing the changes
in blood chemistry that result from inflammation, namely:

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 The Glycine Miracle
1) Increased production and secretion of Factor VII by
the liver. Factor VII is a circulating protein that combines
with the tissue factor (the top of the coagulation cascade)
to initiate the coagulation cascade. When there is more
factor VII around, the blood clots more readily.
2) Increased production, by the platelets, of another
soluble protein called Plasminogen Activator Inhibitor-1
or PAI-1. PAI-1 has been known since 1986 to be part of
the inflammatory cascade as well as the fibrinolytic cas-
cade. That is, the penultimate step in the fibrinolytic (clot
dissolving) cascade, i.e., the activation, by Tissue Plasmino-
gen Activator (TPA) of the pro-enzyme plasminogen to
form active plasmin, is normally inhibited by PAI-1. When
there is inflammation present, the platelets secrete more
PAI-1, thus rendering clots more stable, and thus more li-
able to create a blockage (thrombosis). In 2005, DE
Vaughan at Vanderbilt University in Tennessee, suggested
that PAI-1 was a key player in the formation of blood clots
in heart attack and stroke. Hence, a state of chronic in-
flammation can increase the likelihood of inappropriate
clot formation. That is why patients suffering from car-
diovascular disease typically have blood that is hypercoag-
ulable, i.e., more likely to form inappropriate clots, and
why they are generally prescribed some sort of “blood

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 The Glycine Miracle
thinners,” drugs that inhibit coagulation. Aspirin, for ex-
ample, which inhibits platelet aggregation, is typically rec-
ommended for older individuals with any family or
personal history of stroke or heart attack or other condi-
tion involving inappropriate blood clotting. Prescription
drugs, such as warfarin (which inhibits the liver’s produc-
tion of coagulation factors including Factor VII and pro-
thrombin, and Clopidogrel (Plavix®) which inhibits
platelet aggregation are commonly prescribed as “blood
thinners.” Theoretically, elevation of glycine to a healthy
level, by glycine supplementation, should dramatically de-
crease the risk of stroke and heart attack, and/or recur-
rence of stroke and heart attack, without the use of drugs.
While this is hypothetical at this point for patients who
need to have their blood’s hypercoagulability reduced, it
is certainly harmless for anyone to correct a simple nutri-
tional deficiency, regardless of what drugs they might need.
Certainly the observational studies of Hartiala and
coworkers at the Cleveland Clinic and Ding and coworkers
in Norway point in this direction.

b) Pre-diabetes and Diabetes: Diabetes (specifi-

cally, Type 2 diabetes mellitus) is not usually ascribed to
any sort of injury, but there is reason to hypothesize that

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 The Glycine Miracle
this is the case at the cellular level. Metabolic syndrome
(aka insulin resistance or prediabetes) and diabetes have
historically been ascribed to chronic excess carbohydrates
in the diet, eventually exhausting the beta cells of the pan-
creas from the strain of producing insulin to remove the
excess glucose from the blood circulation. However, since
at least the 1970s, Prediabetes and diabetes were found to
be associated with obesity, specifically, abdominal obesity.
Moreover, the causal link seems very clear, since it is now
known that losing the extra 20 or 30 pounds or more by
diabetic patients actually can reverse the condition. More
recently, researchers have observed an association between
diabetes and markers of inflammation.

In fact, the secretion of inflammatory mediators—cy-

tokines known to mediate inflammation—by abdominal
adipose tissue has been known for over 30 years. In 1993,
GS Hotamisligil and coworkers at the Dana-Farber Cancer
Institute in Boston observed the secretion of tumor necro-
sis factor alpha (TNF-alpha, an important mediator of in-
flammation secreted by macrophages) by adipose tissue in
laboratory rodents. They also observed that neutralization
of the TNF-alpha enhanced the sensitivity of muscle to
insulin, implicating inflammation as a causative factor in

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 The Glycine Miracle
the development of insulin resistance and diabetes. But it
was not until a decade later that Stuart Weisberg and col-
leagues at Columbia University in New York City estab-
lished that the secretion of TNF alpha and other
inflammatory mediators including interleukin-6 (IL-6) was
not from adipocytes (fat cells) in the adipose tissue of mice
and people, but from macrophages embedded in the fat
tissue. This was possible because of technological advance-
ments in the detection of cell surface markers that can dif-
ferentiate between different types of cells and their
origins. Like all macrophages, the adipose tissue
macrophages are immune cells which arise in the bone
marrow and carry the cell surface marker called CD68
(F4/80 in mice).
On the cellular level, Weisberg and colleagues de-
scribed what has come to be known as a “crown-like”
structure. This is the appearance of a large, round, adipose
(fat) cell that appears to be surrounded by a crown-shaped
form. This “crown” is actually a cluster of macrophages in-
volved in the consumption and reabsorption of the adi-
pose cell which has been damaged in some way. These
“crown-like structures” are now known to be a hallmark of
local inflammation in adipose tissue.

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 The Glycine Miracle
In 2010, Naim Alkhouri and colleagues at the Cleve-
land Clinic suggested that apoptosis (cell death; although,
as I have described earlier, the adipocyte cell death going
on here is more like necrosis or pyroptosis; i.e., inflamma-
tory-type cell death) of adipocytes is the first step in the
sequence of events leading to inflammation in adipose tis-
sue, insulin resistance (prediabetes) and type 2 diabetes.
The Weisberg group and others had previously demon-
strated a direct correlation between adiposity (percentage
of body mass composed of adipose tissue) and the average
size of adipose cells. Weisberg et al. had also shown a direct
correlation between adiposity and the percentage of adi-
pose tissue composed of macrophages, ranging from about
10% in lean individuals to about 40% in massively obese
individuals. Hence adiposity, adipocyte cell volume, per-
centage of macrophages in adipose tissue and measures of
inflammation all correlate together. Larger adipose cells
(i.e., adipocytes) are therefore more vulnerable to stresses
which can induce cell death, and so there is more of it.
This attracts macrophages to the tissue to devour the dead
and dying adipocytes. If glycine is deficient, the
macrophages initiate the inflammatory response which
creates more cell death, and the vicious cycle escalates.

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 The Glycine Miracle
While those researching the connection between dia-
betes and inflammation noted above seem to have been
unaware of any role of glycine, the relevance of glycine was
not lost on Cruz and coworkers in Mexico City, who con-
ducted a clinical trial of glycine supplementation in type 2
diabetes in 2008. Specifically, citing earlier work by Gon-
zalez-Ortiz et al. that showed some benefit of glycine in
glucose control, and the work of the Thurman group at
UNC which revealed the glycine-mediated reduction of
the secretion of inflammatory mediators (TNFalpha in
particular) by monocytes (white blood cells which are pre-
cursors to macrophages), Cruz et al focused on markers of
inflammation in their clinical trial, which I summarized
in the previous chapter. Among the dramatic findings in
their study was a result directly related to the question of
adiposity. Specifically, the reduction in hemoglobin A1C in
the glycine treatment group—i.e., the reversal of type 2 di-
abetes in a patient group that was moderately overweight
(BMI between 28 and 29)—was accomplished with no
change in adiposity (represented by the BMI). Hence, the
connection between adiposity, cell death, inflammation,
type 2 diabetes and glycine has been clear since at least
2010. Yet it remains largely unknown!

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 The Glycine Miracle
Yet there is something incomplete in the story about
how abdominal adiposity causes type 2 diabetes. That is,
knowing that the inflammatory cytokine TNFα causes in-
sulin resistance in muscle and fat, and thus makes the beta
islet cells—the cells in the islets of Langerhans in the pan-
creas that actually make insulin—work harder, does not
really explain exactly why the beta cells should ultimately
fail to make insulin at all and eventually die. After all, there
are many bodily cells and organs that suffer from chronic
inflammation, but they don’t all fail in relatively short
order like the beta cells do in type 2 diabetes (or even
sooner in Type 1, which is juvenile onset diabetes).
With so much research attention focused on type 2 di-
abetes, many details of this process have been elucidated
over the last two decades. This research was recently re-
viewed by Wei Ying and coworkers at the University of
California, San Diego. It is now known that the islets of
Langerhans in the pancreas have lots of resident
macrophages, and that the numbers of these macrophages
increase with adiposity (obesity). As adiposity increases,
not only the number, but also the activation from the non-
inflammatory “mend” state (M2), to an active inflamma-
tory “rend” state (M1) increases, with the increased
secretion of cytokines which are pro-inflammatory medi-

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 The Glycine Miracle
ators, especially TNFalpha and Interleukin-1beta (IL-1β).
Moreover, these cytokines, depending upon conditions
which are not so well known, sometimes increase the num-
ber and function of beta cells (remember, these are the
cells that actually make the insulin and which malfunction
in diabetes) and sometimes decrease their function and
promote their apoptosis (cellular demise). Whatever the
details, the cellular and molecular events that happen with
increasing adiposity almost invariably lead to beta cell dys-
function and death and therefore, diabetes. So with all that
research, we are left with more questions than answers,
and a situation that seems—you guessed it—increasingly
complex! Ying et al throw up their hands with such state-
ments as:
“Macrophages can adapt to local environmental cues,
and it is possible that intra-islet resident macrophage pro-
liferation is an adaptive response to pathophysiological
stimuli. However, the factors that mediate this adaptation
remain to be defined.”
As the authors say at the end of this review exercise:
“While much has been learned about macrophage-beta
cell interactions, many important questions remain unre-
solved. What are the triggering events with respect to islet
macrophage proliferation and expansion? Are initiating

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 The Glycine Miracle
signals derived from the beta-cell or are they extrinsic to
the islet?” These are certainly good questions. And you
might think that, since this is all about a common and se-
rious metabolic dysfunction centered on how the body
handles certain nutrients—especially glucose (sugar) and
amino acids—that researchers would be looking to dietary
components; to the role of specific nutrients, for answers.
While there have been studies on fats, studies which im-
plicate saturated fats as contributing to islet inflammation
in diabetes, there has been relatively little effort made in
studying the role of amino acids in this process, even
though amino acids figure strongly in overall islet function
in terms of hormone secretion (especially insulin and
glucagon).
Thankfully, there has been some excellent research fo-
cused on amino acids and their role in obesity and insulin
resistance (pre-diabetes) done by Hong Chang Tan at the
Singapore General Hospital and colleagues at Baylor Col-
lege of Medicine in Houston, Texas. Studying a group of
patients who underwent bariatric surgery for their obesity,
they have been following up on observations of differences
in amino acid profiles that were enabled by the ability to
measure most (16) of them (as well as over 100 intermedi-
ary metabolites and hormones) in a single test, using the

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 The Glycine Miracle
relatively new tool of metabolomics we discussed here ear-
lier. Thus, back in 2009, Christopher Newgard and col-
leagues at Duke University Medical Center in North
Carolina showed that eight of the amino acids (including
the branched chain amino acids leucine, isoleucine and va-
line) were dramatically elevated in the blood serum of
obese subjects, compared to seven amino acids that were
not different from non-obese control subjects. In stark
contrast, only the concentration of glycine was dramati-
cally reduced in the obese subjects. These findings raised
the question of causal sequence, that is, were the differ-
ences in the amino acid concentrations cause or result of
the insulin resistance?
In 2022, when the Tan group in Singapore measured
the glycine levels of patients before, and six months after
bariatric surgery, they found that, in addition to the pre-
dicted decrease in obesity and insulin resistance, the
glycine levels went up to normal (i.e., the same level as
non-obese control subjects) from being 19% below normal.
Importantly, Tan and colleagues also did specific biochem-
ical testing on their subjects, and they found that the rate
at which the bodies of the obese patients synthesized
glycine was 30% below normal. Six months after the sur-
gery, not only had their glycine levels come up to normal,

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 The Glycine Miracle
but so did the glycine synthesis rate. In other words, the
Tan group was able to conclude that the low levels of
glycine found in obese subjects was because of decreased
synthesis, and not from an increased rate of glycine me-
tabolism or decrease in dietary glycine consumption.
Based on these clear findings, Tan and colleagues argue
that the causal chain suggested by their results is: obesity
→ insulin resistance → decreased glycine synthesis → hy-
poglycinemia (decreased blood glycine levels). But this as-
sumes that the glycine levels (and glycine synthesis rate)
are truly healthy in the non-obese subjects. If we assume,
on the other hand, that “normal” glycine levels are low to
begin with (not due to inadequate glycine synthesis, but
inadequate dietary intake), then we would have obesity in
the presence of hypoglycinemia → insulin resistance and
decreased glycine synthesis. This is what I conclude based
on the clinical trial of the Cruz group in Mexico city in
2008, which we discussed here earlier. They tested mod-
erately overweight subjects with type 2 diabetes (which
follows on insulin resistance and characterized by extreme
insulin resistance) not with bariatric surgery, but with 15 g
per day of supplemental dietary glycine. Their inflamma-
tory and diabetic markers declined toward normal after
three months of treatment, but with no loss of weight. Al-

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 The Glycine Miracle
though their HOMA-IR, a standard measurement of in-
sulin resistance, did not come down to normal it was re-
duced toward normal by almost ten percent.
I would therefore argue that the initial, diet-associated
glycine deficiency was the underlying cause of the meta-
bolic disorder (insulin resistance), with obesity being a sec-
ondary cause by generating systemic inflammation in a
hypoglycinemic (low glycine) environment. What Tan and
colleagues showed, then, was that obesity makes hypo-
glycinemia worse by decreasing glycine synthesis.
Glutamine is perhaps foremost among amino acids
that have been studied in relation to diabetes and specifi-
cally to the function of macrophages and inflammation in
the development of diabetes. In the Guasch-Ferré meta-
analysis discussed in Chapter Nine, you will recall that
both blood glycine and glutamine were found to be low in
type 2 diabetics. More recent research on glutamine and
macrophage activation in regards to obesity and diabetes
has been extensively reviewed by Wenkai Ren and col-
leagues of the South China Agricultural University in
Guangzhou. They noted that glutamine is critical to the
activation of macrophages to the M2, or cleanup function,
as opposed to the M1 or inflammatory function, which is
ascendant in obesity and diabetes. Moreover, they traced

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 The Glycine Miracle
the biochemical pathways implicated in this role, and
noted glutamine supplementation might be a useful strat-
egy in the treatment of diabetes, as it has been found to
be beneficial in laboratory experiments.
However, they also noted that (contrary to most of the
amino acids, including glycine) glutamine is mainly synthe-
sized in muscles, whose function is compromised in obe-
sity and diabetes. Therefore, they admit that glutamine
might well be low as a result of the diabetes, rather than a
cause. This is reminiscent of the recent work of the Tan
group, which also showed a decrease in glycine synthesis
as a result of the metabolic disorder (insulin resistance).
As for glutamine, in the typical, muscle meat-rich diet con-
sumed these days in the industrialized world, glutamine
consumption is high—not low. In contrast, glycine acts as
a “trigger lock” on macrophages, preventing their activa-
tion to the M1, proinflammatory functionality. Teasing out
cause versus effect in the measurement of these nutrients
and metabolites is not an easy task, especially when the
“control” or “normal” levels of glycine are taken axiomati-
cally to indicate healthy function. In particular, the Ren
group appears to be entirely unaware of the research im-
plicating glycine deficiency in the development of dia-
betes, and specifically in the function of macrophages,

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 The Glycine Miracle
even though the very mechanism of glycine’s action had
been worked out by the Thurman group two decades prior.
Another amino acid that has been studied for its ben-
eficial effects on diseases rooted in inflammation is the
sulfur-containing amino acid, cysteine. Cysteine is one of
the three amino acids that make up the body’s main an-
tioxidant molecule, glutathione (GSH). GSH has had a
substantial following among life scientists as a key player
in age-related diseases—including diabetes—and aging it-
self. It is attractive in that oxidative damage causes inflam-
mation, and many believe this implicates a lack of GSH as
a cause of chronic inflammation. However, oxidative dam-
age is also caused by inflammation. For example, one of
the poisons produced and secreted by activated (M1)
macrophages to kill invading bacteria is hydrogen perox-
ide. But such poisons also kill normal cells, and cell death
causes more inflammation (if glycine is deficient), and the
vicious cycle becomes chronic. A team of researchers at
Baylor College in Houston, Texas led by Premranjan
Kumar and Rajagopal Sekhar has propounded a theory
called the “power of three.” By this they mean that equally
important in controlling oxidative damage and chronic in-
flammation are GSH, and the two GSH component amino
acids glycine and cysteine. Following this line of thinking

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 The Glycine Miracle
they have conducted successful trials in laboratory rodents
and humans using supplementation with “GlyNAc,” the
combination glycine and N-acetylcysteine (a readily ab-
sorbable form of cysteine).
This line of research is puzzling, however, in that the
authors make no attempt to separate the effects of these
two amino acids individually; they only test the combina-
tion. This is problematic in light of our old friend Ock-
ham’s Razor, which would dictate that if the benefits of
GlyNAc could be achieved by the supplementation of ei-
ther amino acid alone, then the other can be dismissed as
the principal player. In fact, the benefits the Kumar and
Sekhar group obtain have been observed with just glycine
supplementation alone. Add to that the fact that cysteine
(and methionine, from which it is derived) is abundant in
muscle meat, so the idea that the typical omnivorous could
produce a cysteine deficiency can be dismissed. There is
more to the story of GSH, however, and we’ll take a deeper
look at GSH and the Kumar and Sekhar team’s work in a
later chapter. Getting back to the case of diabetes specif-
ically, we may again recall that the 2008 clinical study of
Cruz et al demonstrated that glycine supplementation
alone could reverse type 2 diabetes.

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 The Glycine Miracle
But unfortunately, most of the effort in terms of look-
ing for substances that help to normalize islet function is
in looking for drugs, especially anti-inflammatory drugs.
So there has been research on NSAIDS (non-steroidal
anti-inflammatory drugs), such as the aspirin-like drug sal-
salate, or TNFalpha inhibitor “biologics”—which are bio-
engineered antibodies to TNFalpha (e.g., etanercept,
adalimumab) or IL-1β (e.g., canakinumab). These drugs
have now become ubiquitous features of television adver-
tising for inflammation-based conditions such as arthritis
and Crohn’s disease. They are necessarily injectable (be-
cause they are proteins, which would be destroyed by the
digestive system if ingested orally) and increase the risk of
all sorts of infections. That’s because they are antibodies
designed to impede the normal function of macrophages
in destroying infectious microbes. How healthy can the
population be if the use of drugs which weaken the im-
mune system are widely and chronically used?
And let’s not forget that all this research in recent years
is in the shadow of the Mexico City clinical trial in 2008
(Cruz, et al), a successful trial of supplementation with or-
dinary glycine.

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 The Glycine Miracle
c) Nonalcoholic Fatty Liver Disease (NAFLD)
While we are on the subject of type 2 diabetes, it is a
good point to address the very closely related co-morbidity
of NAFLD. Actually, NAFLD encompasses several closely
related co-morbidities, the most common being nonalco-
holic steatohepatitis (NASH). These conditions are char-
acterized by fatty accumulations, inflammation and
scarring (fibrosis) in the liver, which can lead to cirrhosis
and liver failure. It is also characterized by insulin resist-
ance. NAFLD is very common, estimated to affect 25% of
the world’s population. The advent of metabolomics,
which enables the measurement of up to hundreds of
metabolites in the blood simultaneously, has provided a
great deal of information about the metabolic defects as-
sociated with NAFLD. Thus, in 2018, Melania Gaggini at
the National Research Council in Pisa, Italy and colleagues
at the University of Turin, detailed differences in the pro-
file of metabolites—especially amino acids—between nor-
mal and both obese and nonobese NAFLD patients.
Unsurprisingly, while several amino acids were elevated,
glycine in particular was lower in the patients compared
to healthy controls, especially in the NAFLD patients who
were also obese. As usual, it was not possible to pinpoint
the causal chain of events in the development and progres-

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 The Glycine Miracle
sion of disease. In 2020, however, Oren Rom and col-
leagues at the University of Michigan zeroed in on glycine.
Noting that “Lower circulating glycine is consistently re-
ported in patients with NAFLD,” they aimed to investi-
gate “the causes for reduced glycine, its role as a causative
factor, and its therapeutic potential.” Using human liver
biopsies and laboratory mice, they tested the activities of
genes (using transcriptomics, which like all the other “-
omics” methods, enables the measurement of many
mRNAs simultaneously, to determine which genes are ac-
tively coding for the synthesis of particular enzymes) in
NAFLD mice and people, compared to normal. As the Tan
group in Singapore reported in patients with obesity in
2022, the Rom group also found that the synthesis of
glycine was impaired in NAFLD. In particular, they iden-
tified a defect in the synthesis of glycine by one particular
pathway in the liver, which utilizes the enzyme called ala-
nine-glyoxylate aminotransferase (AGXT). There actually
are many people (especially of northern European descent)
with genetic variants of the gene for this enzyme. I suspect
that such people, with decreased capacity to synthesize
glycine by this route, may be more prone to have a dietary
glycine deficiency show up as NAFLD. The Rom group
took the next logical step of using glycine therapy to treat

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 The Glycine Miracle
the illness in their experimental mouse model, based on
experiments done back in 2004 by Mohammed el Hafidi
and colleagues in Mexico City. Just as glycine feeding had
protected el Hafidi’s rats from developing NAFLD-like ab-
normalities, glycine-based therapy normalized all the abnor-
mal biochemical indicators in the Rom group’s study. Their
approach was a bit different than just using glycine in that
they sought out compounds—essentially small peptides
(short chains of a few amino acids) to do even better than
plain glycine. They settled on a compound they called DT-
109, a tripeptide (three amino acid groups) consisting of two
glycine units and one leucine unit. They found that this
compound was even better than glycine alone in helping to
regulate both sugar and fat in NAFLD mice. Of course, DT-
109 is digested to release the free amino acids (mainly
glycine), so it is really another way to supplement with
glycine. Why Rom et al focused on synthetic compounds,
however, rather than just ordinary, natural glycine, is an-
other reflection of what I have referred to as a drug men-
tality in the medical and medical research communities. It
should be noted that although the Rom group did not re-
ceive any funding from pharmaceutical companies, the drug
orientation of researchers is very prevalent these days.

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 The Glycine Miracle
d) Micro Injuries causing chronic pain as long-

term consequences of significant injuries:

It has long been known that substantial injuries, such
as from war wounds or motor vehicle accidents, result in
chronic pain years or decades after the initial injuries have
healed. The treatment of such chronic pain is a major
source of opioid addiction, as opioids are typically pre-
scribed to treat such chronic pain. The fact that so many
such people have had these pains substantially reduced or
eliminated entirely via glycine supplementation has led me
to embrace the following hypothesis:

Substantial injury often heals with the creation of scar tissue.

Scar tissue is much less flexible than the soft tissue it replaces. There-
fore, though long healed, formerly wounded joints, for example,
when flexed, give rise to small tears: micro injuries that provoke
inflammation and hence pain, as long as glycine is deficient.

Here are a few stories from people whose chronic pain

was alleviated or eliminated by daily consumption of Swee-

tamine®, the glycine supplement I formulated and cur-

rently market:

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 The Glycine Miracle
“Having worked in construction, I had been suf-

fering terribly with back and shoulder injuries for 17

years. All in all, I have had to endure six shoulder sur-

geries, five spinal surgeries and another dozen outpa-

tient procedures. This left me with intense chronic

pain, requiring me to take eight doses of opioids (mor-

phine and Percocet) every day to get through the day,

for the last several years. Then my brother heard you

on the radio, and he said ‘You oughtta try this stuff.’

So I did, and after about a week of Sweetamine (two

stick packs per day), I started to feel incredible relief

from the pain and immobility, and have cut my use of

painkillers literally in half. I feel like I have my life

back.” Anthony, Pico Rivera, CA

“My wife and I have been adding Sweetamine to

our morning hot oatmeal for about 7 days, it gives

sweetness to the dull tasting oatmeal. I had an old

right ankle injury a few years back and developed

chronic pain when I make a wrong step, the pain

comes and goes, and I have been told by an Orthopedic

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 The Glycine Miracle
Surgeon that soon I will need arthroscopic surgery.

Now I noticed that the ankle acts more stable and I

feel no pain when walking.” Tad, Mission Viejo, CA

I hear many such stories from Sweetamine consumers,

including those who have had joint replacement surgeries:

“My wife and I have been using sweetamine for

over a year now and we love it. We’re 73 years old and

are virtually pain free. I had shoulder replacement

surgery last year shortly after starting on sweeta-

mine. Even my surgeon was impressed with the speed

of my recovery.” John, Georgetown, TX

And those who were told by doctors that they would

need joint replacement surgery, until they tried Sweeta-
mine, which ended their pain and immobility:

Had three years of swelling and issues with my right

knee. Some days, I couldn’t walk at all, or had to use

a walker. I finally got an MRI in May, and I was told

that I needed a full knee replacement. I started taking

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 The Glycine Miracle
Sweetamine, and within two weeks there was no

swelling and no more pain! Dee, Surprise, AZ

“I can’t say enough good things about Sweeta-

mine! I can move now, I don’t have any pain in my

knees. They told me I had osteoarthritis; that it was

bone-on-bone and I would probably need knee re-

placement surgery, but I feel great now” Pilar, Stock-

ton, CA

Chronic brain injury resulting from head trauma:

These days there is increasing concern about sports in-
juries and other forms of head trauma, as they often result
in concussions and chronic encephalopathies of various
sorts. Just as chronic inflammation resulting from normal
cell death in brain development may produce brain abnor-
malities characteristic of autism, the inappropriate inflam-
mation following traumatic injury to the brain may well be
responsible for the rising tide of encephalopathies. Here
again I will rely on some of my own personal self-experi-
mentation experience to describe what does not happen,
when glycine is not deficient.

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 The Glycine Miracle
Six years ago (at age 67), after allowing myself to become
dehydrated, not drinking water all day and having a glass
of wine after a three-hour drive, I got up quickly from a
seated position and fainted. Unfortunately, I fell with my
head hitting the square corner of a hardwood kitchen table
on the way down. After several seconds I came to lying on
the floor on my back, and in a state of some mental con-
fusion for a minute or so. I also had a really bad headache
where my head had struck the table. Fortunately, this was
at the home of, and in the presence of my grown son and
daughter, who quickly called 911, and I was whisked off to
the hospital ER within the hour. Within two hours of the
trauma, the pain at the spot of impact on my head was
gone completely. The mental confusion I had upon regain-
ing consciousness lasted no more than a minute or two.
No other symptoms occurred or persisted beyond two
hours at all. Nor have any occurred since.
Also, a member of my extended family had suffered a
concussion from a blow to the head while playing hockey.
She had recurrent headaches which persisted at least for
several weeks. But after taking the Sweetamine glycine
supplement for a few days, the headaches disappeared.
Such chronic inflammation may well be responsible for
various forms of age-related dementia, which are also on
the rise.
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 The Glycine Miracle
e) “Type 3 Diabetes.”
The question of brain damage resulting from chronic
injury—really, from inappropriate inflammation in re-
sponse to injury—brings to the fore the question of age-
related dementia, such as Alzheimer’s Disease. Specifically,
we may ask, is age-related dementia also a result of inap-
propriate inflammation, due to glycine deficiency? This ac-
tually brings us back to the subject of type 2 diabetes, the
association of which with dementia has recently earned
Alzheimer’s Disease the nickname: “Type 3 diabetes.”

It is difficult to pin down the origin of the term “Type

3 Diabetes,” which popped up in several places during the
early years of the 21st century. Suzanne de la Monte of
Brown University suggested the term in 2014; however,
Zina Kroner of the American Board of Internal Medicine
mentioned earlier references to the term in her 2009 re-
view. Regardless, it is clear that many researchers have
noted the endocrinological and biochemical similarities
between insulin resistance and other dysfunctions ob-
served in muscle and other tissues in Type 2 diabetes and
brain abnormalities in those with Alzheimer’s Disease.
Moreover, the epidemiological (i.e., statistical) association
between diabetes and Alzheimer’s Disease has been appar-

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 The Glycine Miracle
ent since at least 1999. This association has been the sub-
ject of several systematic reviews and meta-analyses
(SRMAs), such as that published in 2009 by Feng-Ping Lu
and colleagues at the National Taiwan University Hospital
in Taipei. They reported a significant, overall 47% in-
creased risk of dementia among patients with type 2 dia-
betes, compared to non-diabetics. Specifically, the average
risk increase was 39% for Alzheimer’s disease and 138% for
vascular dementia. It is not surprising that both common
forms of dementia correlate. (Vascular dementia is often
referred to as multi-infarct dementia; a result of multiple
“mini-strokes;” episodes of small blood vessel blockages in
the brain. This is in contrast to Alzheimer’s disease, where
the primary damage is directly to the neurons of the brain
themselves, rather than to their blood supply.) After all,
both are characterized by (among other normalities) some
form of inflammation, whether in the brain tissue itself
(instigated by microglia, the brain macrophages) or
macrophages in the blood and blood vessel walls.
In 2016, EM Ribe and F Lovestone of Oxford Univer-
sity in the UK noted: “links between insulin and IGF-1 sig-
naling and the Alzheimer’s disease-associated pathological
events as well as the impact of other processes such as in-
flammation, oxidative stress and mitochondrial dysfunc-

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 The Glycine Miracle
tion are either common to both conditions or perhaps re-
sponsible for a mechanistic link between metabolic and
neurodegenerative disease.”
Now there is general agreement not only that diabetes
and dementia are functionally related, but also obesity and
other such “pre-diabetic” conditions, specifically insulin
resistance (sometimes referred to as “metabolic syn-
drome”) and non-alcoholic hepatic steatosis (NASH).
However, there are different hypotheses proposed con-
cerning causation, some putting more credence into aging,
diet and obesity, and some others suggesting that various
forms of oxidative stress may be more to blame. De la
Monte, for example, makes the case that the primary in-
sult responsible for these related conditions is the specific
type of oxidative damage caused by nitrosamines. Both en-
vironmental and dietary exposure to these toxins (and
known carcinogens) has increased substantially in the
Western world in recent decades, along with the increased
incidence of diabetes and dementia. How then, do we an-
swer the question as to which insult is primal in the chain
of events leading to these diseases?
Inflammation is increasingly recognized to be the com-
mon denominator. For example, as we have seen with the
work of Cruz et al in 2008, we can definitively assign to

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glycine deficiency the cause of diabetes, since it can be re-
versed with glycine supplementation alone, and since this
reversal does not involve any decrease in body weight.
Rather, obesity increases the level of systemic inflamma-
tion when glycine is deficient. Hence, while obesity is
clearly causally related to diabetes, it is secondary to
glycine deficiency, and exacerbates glycine deficiency by
reducing glycine synthesis. We have also seen that cardio-
vascular disease (which would also include multi-infarct or
vascular dementia) is also characterized by low glycine lev-
els. As far as oxidative damage is concerned, it is known
that oxidative damage can cause inflammation, but so can
virtually any kind of cellular damage provoke the activa-
tion of macrophages to cause inflammation in the pres-
ence of glycine deficiency. Ultimately, the
medical/scientific community will require proof in terms
of glycine supplementation’s ability to prevent or reverse
any or all of these inflammation-related conditions, before
the glycine hypothesis is accepted.
This raises yet another question, namely, in what meas-
ure can glycine supplementation actually reverse any of
these conditions? In the Cruz clinical trial, for example, it
is clear that diabetes is reversed—with the average hemo-
globin A1C dropping from 8.3 to 6.9 (i.e., diabetic to non-

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 The Glycine Miracle
diabetic levels). However, all the patients remained on
their anti-diabetic medications. Would their diabetes be
completely reversed if the medications were withdrawn?
This cannot be determined, of course. Yet it is reasonable
to assume that what glycine supplementation achieves
completely is the cessation of inappropriate inflammation.
But the actual presence of disease reflects some measure
of chronic damage resulting from chronic inflammation.
Hence, the sooner the glycine deficiency is corrected, the
less damage (especially to the pancreatic islets, where the
insulin is made) and therefore, the more complete the re-
covery can be.
But when it comes to type three diabetes, reversal of
the condition of dementia may not be possible at all, since
once brain tissue is actually destroyed, it may be unable to
be regenerated. Not that there is no regenerative capacity
in the brain, but by the time cognitive deficits are clearly
observable, the disease process has likely been going on
for many years, and typically all this is happening at an ad-
vanced age, at which regenerative capacity may have been
lost for the most part. Thus, in the few cases I have wit-
nessed wherein supplementation with glycine (Sweeta-
mine) commenced, it offered no improvement after
substantial cognitive decline had been diagnosed.

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 The Glycine Miracle
4. Inflammation that is an overreaction to infection

by various microbes, whether viral or bacterial

I have several examples of this, mostly from my own
experience, self-observation and self-experimentation, as
well as the anecdotal experiences of others. However, it all
fits into the coherent picture of glycine action and inflam-
mation that has emerged from the medical literature, as
detailed above.

a) Gingivitis/Periodontitis
I had been plagued by this condition for most of my
adult life. Annual or semiannual cleanings at my dentist’s
office were always painful and bloody affairs, with deep
sulci (pockets) forming around many of my teeth, several
of which were lost to infection along the way. But after
daily glycine supplementation, at some point, my dental
cleaning visits ceased to be painful or bloody. And the over-
all condition of my gums actually improved over time.
From this change I conclude that the populations of bac-
teria that normally inhabit my mouth—and especially
deep in my gums around my teeth—are simply not pro-
voking the inflammation that characterized the ”normal”
state in my mouth in my pre-glycine days. Adding to the

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 The Glycine Miracle
evidence of the relevance of glycine deficiency in peri-
odontitis, in 2005 Caroline Riben-Grundstrom and col-
leagues in Sweden demonstrated the ability of therapeutic
glycine to ameliorate periodontitis that developed after
dental implants. The importance of glycine in periodontal
health may also have implications for cardiovascular
health, in that researchers have noted that such conditions
as gingivitis are statistically linked to cardiovascular dis-
ease (CVD). This subject was reviewed in 2020 by Ric-
cardo Nocini of the University of Verona, Italy, and
colleagues. They noted that one mechanism underlying the
statistical association between periodontitis and coronary
heart disease (CHD) may be the translocation of bacteria
to the heart and vascular tissue, and their accumulation
within atherosclerotic plaques, rendering plaques more un-
stable and prone to cause ischemic events (heart attacks).
We may hypothesize here that inflammation, which char-
acterizes both gingivitis and atherosclerosis may be pro-
voked unnecessarily in both locations (mouth and
coronary arteries) due to glycine deficiency. This hypoth-
esis is also supported by the Norwegian research cited ear-
lier by Ding et al. linking adverse cardiovascular events
(heart attacks) to lower glycine levels. Hence it may well
be that inappropriate inflammation may be instigated by

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 The Glycine Miracle
both micro-injuries in the coronary arteries as well as the
presence there of otherwise harmless bacteria.

b) Shingles
It is common knowledge that shingles is an adult dis-
ease caused by an infectious agent, specifically the Herpes
zoster virus, which is the same pathogen that causes chick-
enpox in children. Shingles is thus a resurgence of a child-
hood infection, the virus remaining latent for many years
or decades, before symptoms and frank disease appear.
The disease typically presents with a unilateral rash—typ-
ically on the lower back but sometimes occurring on the
neck or face. The rash is characteristic and typically very
painful, often described as the skin’s being “on fire.” The
condition also typically lasts for a month or two, and is
sometimes debilitating. There is therefore substantial pro-
motion of shingles vaccines (e.g., “Shingrix®”), especially
to older people, who have the highest prevalence.
I got a case of shingles myself in 2015, so daily eight to
ten grams of supplemental glycine did not prevent shin-
gles. And my case was classic in that it produced a charac-
teristic unilateral rash on my lower back (with the
diagnosis confirmed by my neurologist. “Classic” was the
word he used to describe it.) But what was unusual was

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 The Glycine Miracle
that I did not feel the rash at all. In fact I had only discov-
ered it while bathing in the shower one morning and hap-
pened to feel the bumpy surface of the rash with my
fingers. Therefore, although my shingles ran the usual
course of almost two months, it never caused me any pain,
although there was a mild, generalized malaise typical of
many viral infections, and was therefore merely a minor
nuisance. It was certainly not a disease I would ever con-
sider using a vaccine to prevent.
This encounter with shingles led me to hypothesize
that the pain usually caused by shingles is actually due to
local inflammation, inappropriately set off by the infection
in the absence of adequate glycine. This thinking is also in
the context of hearing about similar types of relief from
pain of secondary inflammation. One customer of mine
suffers from periodic flare-ups of gout. Gout is a painful
condition due to a metabolic imbalance that causes the
crystallization of the metabolite uric acid in capillaries
around joints. Hence the flare-up is mainly due to the in-
flammation resulting from micro-injuries caused by the
uric acid crystals. But when glycine is adequate, the flare-
ups produce minimal discomfort.
Another customer is a young lady who suffers from sys-
temic lupus erythematosus (SLE). She has reported that

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taking daily Sweetamine enables her to flex her fingers first
thing in the morning without pain. Whether glycine has
any direct benefit in terms of ameliorating the disease
process in SLE, which is an autoimmune disease, is un-
known. My hypothesis is, again, damage caused by the dis-
ease process produces secondary inflammation when
glycine is deficient.
Another such situation may be presented by allergy. I
used to be exquisitely sensitive to poison ivy. Even the
slightest touch of a poison ivy leaf anywhere on my skin
would provoke the characteristic, delayed hypersensitivity
allergic reaction: hard, white bumps that were very itchy
and made me scratch them, making it all worse, of course.
But sometime after taking 10g/day of supplemental
glycine, it seemed that light, casual contact with poison
ivy produced no major reaction.
So I tried an experiment: Handling a freshly plucked poi-
son ivy leaf with my (gloved!) right hand, I rubbed the leaf
against the back of my left hand. Afterwards I just washed
my hands normally—without any special soap or solvent to
wash out the poison ivy oil that persists in the skin.
Sure enough, a day or two later, the back of my left
hand flared up with the typical poison ivy reaction. It
looked just as ugly as any poison ivy rash had ever looked

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on my skin. However, the itch was minimal and actually
went away soon after the rash had formed. Hence the rash
never got exacerbated by scratching it. Within several
days, the rash followed its typical course of disappearance,
but all the while it did not itch.

c) Covid 19 Pneumonia
Back to the subject of viruses and glycine, we cannot
skip over the viral pathogen of the recent pandemic, Covid
19. Covid 19 provides a perfect example of a case wherein
most of the damage—life-threatening damage in millions
of cases during the recent pandemic—is caused by inflam-
mation. The severe inflammation, the pneumonia caused
by Covid 19 is now typically described as a “cytokine
storm” of inflammation that pervades the lungs and often
kills rapidly. It is also noteworthy that, after many months
of trying different treatment modalities, the standard pro-
tocol has become centered around a course of the anti-in-
flammatory steroid, prednisone.
From the glycine perspective, the common comorbidi-
ties are all conditions characterized by decreased glycine
levels: obesity, diabetes, cancer, and most prominently, ad-
vanced age. Could it be that Covid 19 is only a life-threat-

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ening disease because it provokes inflammation in alveolar
macrophages, and only when glycine is deficient?
Considering my long-standing regular consumption of
supplemental glycine as an ongoing self-experiment, more
results manifested when I myself became infected with
Covid 19 (likely the delta strain of 2021).
As it had been with shingles, my symptoms were quite
characteristic of the disease (which was confirmed by a
positive rapid antigen test (Carestart). After a few days of
testing positive, I had, in addition to general malaise, a
fever of almost 102 F and diarrhea, both of which lasted
less than 24 hours. There were also appetite changes that
persisted for some weeks. The malaise persisted for two
weeks and gradually subsided completely after another
week. I also progressively lost my sense of smell, which
was complete for a few days before gradually returning. All
in all, I felt quite miserable for about three weeks, like I
had a nasty intestinal virus. I needed about 12 hours per
night of sleep, but was not bedridden, so overall, I would
have to characterize my disease as moderate at worst.
But there was one glaring set of symptoms usually en-
countered with Covid that was completely absent: I had
no respiratory symptoms whatsoever. No coughing, no
sneezing, no wheezing, no shortness of breath. Later, in

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checking with various friends and family, those taking the
Sweetamine glycine supplement, also had no serious dis-
ease, even those who were older (65+), and one who had
even had lung surgery a year or two prior to Covid. One
particular anecdote stands out: A friend of mine’s dad—in
his 70s—was hospitalized with Covid, and he was not
doing well. His dad was on a ventilator for 12 days, as he
begged the hospital not to take him off it. Finally, they dis-
charged him and sent him home, but he was so weak, he
literally could not get out of bed. I suggested that Sweet-
amine might help, and brought some to his house. He sub-
sequently called me and said it was like a miracle: He fed
his dad the Sweetamine in his tea in the evening, and the
next morning, he just got up and went about his business!
Of course, this is only one anecdotal report. There was,
however, a clinical trial of glycine administration interven-
tion conducted by Mario Vargas and colleagues in Mexico
City, on 56 severe Covid patients admitted to hospital for
mechanical ventilation in the ICU, and no clinical benefit
was obtained. However, the glycine was administered
through a nasogastric feeding tube, and no increase in
blood levels of glycine was observed. Hence it is clear that
the administered glycine was not absorbed, forcing the au-
thors to admit that a “possibility for the lack of effect of

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glycine was that the critical condition of patients impaired
the enteral absorption of glycine and in this case, perhaps
glycine administration by the intravenous route might
have been a better approach.”
Then of course, there is what has become known as
“long covid,” mainly characterized by persistent muscle
weakness, but also cognitive and systemic impairments.
The common denominator seems to be—you guessed it:
inflammation! As of mid-2024, at least three dozen re-
search articles have appeared in the literature about in-
flammation in long covid. The PHOSP-COVID
Collaborative Group in the UK reported in the top med-
ical journal Lancet Respiratory Medicine that only one in four
patients who had been hospitalized for Covid-19 had re-
covered completely within five months of hospital dis-
charge. More alarmingly, none of the patients still affected
had recovered within an entire year! The authors also
noted that “several inflammatory mediators were in-
creased in individuals with the most severe physical, men-
tal health, and cognitive impairments compared with
individuals with milder ongoing impairments.” They fur-
ther concluded: “Both pharmacological and non-pharma-
cological interventions are urgently needed to improve the
ongoing burden following hospitalization for COVID-19

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 The Glycine Miracle
both for individuals and healthcare systems. Our findings
support the use of a precision medicine approach with po-
tential treatable traits of systemic inflammation and obe-
sity.”
Could it be that all these patients need is supplemental
glycine? The evidence certainly points in that direction,
with inflammation being the central common feature of
long covid. But, alas, such simple explanations seem to
elude the most knowledgeable clinical experts: As Lidiane
Florencio and César Fernández-de-las-Peñas of the Uni-
versity Rey Juan Carlos in Madrid reported almost simul-
taneously in the same journal (citing the same data from
the PHOSP-COVID group), “Management of the post-
COVID-19 condition—often referred to as long
COVID—is a challenge for health-care professionals be-
cause of the heterogeneity and complexity of its clinical
manifestations and the probable need for multidisciplinary
management approaches.” It would seem that apparent
complexity immediately rules out the possibility of a sim-
ple solution for these doctors. They are likely unaware that
their mindset is completely unscientific—even anti-scien-
tific! Another iteration of this flawed logic in relation to
long covid (although it is pervasive among medical science
researchers and practitioners these days) was articulated

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 The Glycine Miracle
in the 2023 paper by Bianca Besteher and colleagues in
Jena/Magdeburg Germany. In their summary of their work
on cognitive deficits in long COVID patients, they wrote:
“As the heterogeneity of symptoms is increasingly recog-
nized among long-COVID patients, it appears highly rel-
evant to study potential pathophysiological differences
among the different subtypes.” After summarizing their
findings in different subgroups of their patients, they con-
clude: “This implies a complex underlying pathomech-
anism in long-COVID and emphasizes the necessity to
investigate the whole spectrum of post-COVID biology to
determine targeted treatment strategies targeting specific
sub-groups.” What this thinking means, in general terms,
is that when seeking to understand any set of phenomena,
a multiplicity of diverse effects implies that the underlying
cause is complex, and therefore the treatment must em-
body a diverse array of treatment strategies. But as a scien-
tist, I look for the common factor that underlies all the
diverse manifestations. They already know and acknowl-
edge the common factor of inflammation, but even this is
seen as bewilderingly complex. Just imagine if a meteorol-
ogist, in seeking to understand the weather phenomenon
of precipitation, believed that one needed to separately
study rain and snow and sleet and hail, as if they had noth-

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 The Glycine Miracle
ing in common! My hypothesis, based on inflammation
being found as a culprit in every study of long COVID is
that Long COVID is indeed just another glycine deficiency
disease (as is acute COVID pneumonia).

d) Viral infections in general

In fact, my Covid experience led me to expand my hy-
pothesis that had been suggested by my shingles experi-
ence: Many viruses—perhaps viruses in general—are really
relatively harmless unless glycine-deficiency is present. It
is intriguing to consider that so many potentially deadly
viruses do not universally cause serious disease, or no dis-
ease at all. Consider for example, the hepatitis B virus, and
C virus, infection with which is often asymptomatic until
liver cancer develops years or decades later. What about
human papilloma viruses (HPV) which can cause cervical
cancer years later—or not? What about HIV, long feared
as a death sentence, which also does not produce disease
among a significant fraction of infected individuals?
Though not generally known, this was also the case for the
viral disease, polio (poliomyelitis).
I was among the first generation to receive the Salk
polio vaccine to prevent the scourge that was rampant
until the 1950s in the United States. But in fact, before the

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 The Glycine Miracle
vaccine was available, most American kids got polio. How-
ever, it was typically experienced as just another cold.
Could it be that glycine was the difference between an in-
significant infection and death or lifelong paralysis? Even
the dreaded Ebola virus also produces no disease (only im-
munity) in a majority of those infected. Are viruses in gen-
eral no more than a nuisance in the absence of glycine
deficiency? Even more generally, a host of bodily irritations
including viral and bacterial infections, and also environ-
mental insults, such as cigarette smoking, asbestos inhala-
tion, are only harmful because they cause injuries, which
in turn, provoke inflammation. This can cause serious dis-
ease and even death when acute, such as in Covid 19 in-
fection, or ultimately cancers when chronic.

5. Inflammatory conditions with unknown causes

Migraine headache
Headaches may follow on traumatic injury, with long-
term consequences, as we have discussed. But there is also
a very common type of headache not apparently related
to traumatic injury, but nevertheless a product of inflam-
mation, namely, migraines. Migraines are now known to
be a specific consequence of one of the major inflamma-
tory cytokines we have seen before in this book: Tumor

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 The Glycine Miracle
Necrosis Factor alpha (TNFα). Elevated concentrations
of TNFα have been observed in the blood of patients with
migraine since the 1990s, and V. Covelli and colleagues at
the University of Naples, Italy, have correlated the pres-
ence of bacterial marker molecules (lipopolysaccharides,
characteristic of bacterial cell walls) with TNFα in mi-
graine as well. Hence there is the suggestion that the initial
inflammation-provoking insult might be a low-grade bac-
terial infection. It is also particularly interesting that sev-
eral inflammatory conditions are seen as comorbidities in
migraine. As observed by Amrit Sudershan and colleagues
in Srinagar, India, in their extensive 2024 review of TNFα
in migraine: “Patients with psoriasis, inflammatory bowel
diseases (IBD), and rheumatoid arthritis have a higher risk
of migraines.” They also detailed the partial successes with
anti-TNFα drugs in recent years as well as the progress
made in understanding the sequence of events in the acti-
vation of the microglia (brain macrophages) to cause in-
flammation.
But unfortunately, as we have seen before, Sudershan
et al. seem to be swept up in the apparent complexity of
the inflammatory basis of migraine, rather than seeking a
common molecular denominator; a simple solution. “Mi-
graine is a complex disorder,” they say, as they highlight

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 The Glycine Miracle
what they say is the need for “continued research for the
discovery of genetic, epigenetic, and molecular biomark-
ers, which help for identifying the diseases and also moti-
vate personalized medicine to treat migraine.” Never does
the word glycine enter their discussion, a fact which is cu-
rious as they defer to the classical understanding of mi-
graine as expressed by Rami Burstein and co-workers at
Harvard, including the fact that the “lower threshold of
neuronal hyperexcitability, is the reason for the migraine
attack initiation.” I say curious, since, as I explained earlier
in this book, one of glycine’s natural roles as an inhibitory
neurotransmitter in the brain is to prevent neuronal hy-
perexcitability. Then again, one should not be too sur-
prised to see clinicians (again!) fall into the non-scientific
trap of complexity, given even the title of one of Burstein
et al.’s classic papers on migraine in 2015, published in the
Journal of Neuroscience: “Migraine: multiple processes,
complex pathophysiology.”

One can find glycine appearing sporadically in the mi-

graine literature, however, in the context of measuring
CNS neurotransmitters in cerebrospinal fluid, blood or
saliva. Importantly, glycine is not only an inhibitory trans-
mitter in the CNS, but also a co-activator (co-transmitter)

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 The Glycine Miracle
with glutamate, which together act as excitatory neuro-
transmitters. Back in the 1990s, JF Rothrock et al. at the
University of California, San Diego (UCSD; 1995), Z Alam
et al. at the University of Birmingham in the UK (1998)
and C Rajda et al. at the Albert Szent-Györgyi Medical
University in Szeged, Hungary (1999) measured elevated
levels of glycine and glutamate in CSF (cerebrospinal fluid;
the fluid which circulates inside the brain and spinal cord),
blood plasma and saliva, respectively in patients with mi-
graine. Those findings of course raise the question as to
which role of glycine—neuroexcitatory or neuro in-
hibitory—is represented by elevated levels in migraine pa-
tients. It also raises the treatment-oriented question as to
whether supplementation with glycine will make things
better or worse.
As to the former question, the likely answer emerged
in research conducted by Martina Curto at Harvard and
her colleagues in Rome, Italy. They looked at metabolites
in the kynurenine pathway, a sequence of biochemical con-
versions of molecules of the amino acid tryptophan, which
occur in the brain. In this pathway, tryptophan is con-
verted into the amino acid kynurenine, at which point
there is a fork in the road. One path produces kynurenic
acid, while another results in the formation of anthranilic

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 The Glycine Miracle
acid. In migraine patients, Curto and colleagues found that
most of the kynurenine was converted to anthranilic acid,
thus drastically reducing the formation of kynurenic acid.
Importantly, kynurenic acid is a key inhibitor of glycine’s
action as an excitatory co-activator. Consequently, its re-
duction results in the increase of excitatory transmission.
In other words, the natural inhibition of glycine’s excita-
tory role is reduced in migraine. This supported the au-
thors’ hypothesis that migraine is a disorder in which
excitatory neurotransmission is increased.
As to the latter question, there seems to be nothing in
the literature regarding glycine supplementation in mi-
graine, but anecdotally, my own daughter who suffered mi-
graines a few times per year, no longer gets them at all,
taking 8 grams of glycine per day. And some of my Sweet-
amine customers have reported dramatic benefits in their
unsolicited testimonials:

Annie in Cave Creek, writes:

“THANK YOU. Love your product. I’ve been a

chronic sufferer of migraines for most of my life. I am

a 35 year old mom of three who has a very healthy diet,

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 The Glycine Miracle
exercises, and keeps my weight down, but I couldn’t

get my headaches to improve. I wrecked my stomach

using Advil like candy to get by, but it never cured or

removed my headaches. I knew my headaches were in-

flammation related because of stemming from my

neck muscles and feeling like I always needed to pop

my back. I saw numerous specialists and chiroprac-

tors but nothing helped. I changed my diet to reduce

inflammation, but still, they persisted. I started tak-

ing Sweetamine and within days I felt like my

headaches were gone. I thought NO WAY— too good

to be true. Week THREE NO head aches. I am a be-

liever! I am elated with this product. I tell everyone

I can about it.”

Dustin from Charlotte, NC writes:

“I first heard of your product on the radio. At the

time I was skeptical at best about its efficacy, but I

have suffered from a lot of inflammatory illness (Celi-

acs Disease, Leaky Gut, Spondylosis etc.), and I

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 The Glycine Miracle
thought I would try out your product for a couple of

weeks to see if it would help with back and joint pain.

What I did not expect was the effect it would have on

my migraines. To give a little context, for the last fif-

teen years I have suffered from increasingly

severe migraines that have been diagnosed as hemi-

plegic, where one side of my face and body will occa-

sionally become paralyzed for short periods of time.

At the time I ordered my first package of Sweetamine,

I was on average getting one to two migraines a week,

if I was lucky. Since I have been using Sweetamine

every day, I don’t think I have had one serious Mi-

graine in four months. For me your product has

worked wonders, completely curing my migraines,

and freeing me from a great deal of back and joint

pain. Thank you for creating this product. “

Note also how the benefits of glycine came as a sur-

prise to Dustin, confirming what I mentioned earlier
about the correlations between known inflammatory dis-
eases and migraine.

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 The Glycine Miracle
b) Inflammatory Gastrointestinal disease
Inflammatory conditions such as Crohn’s disease are
very prevalent nowadays, but there is nothing in the recent
literature I can find that references glycine in this context.
One would think that glycine supplementation might help,
and I have received some unsolicited testimonials from
Sweetamine customers suffering from such conditions.
Thus, Mackenzie of Cleveland, Ohio, writes:

“I have Crohn’s and arthritis, for which I had been

taking steroids for some time. But the steroids were caus-

ing so many side-effects, I went off them. But then, my

arthritis got so bad that I would wake up in the morning

and everything hurt really badly: my arms, my legs, every-

thing. Then I tried Sweetamine. I took two packets a day,

and within two days, most of the pain was gone. It was

amazing; A-MAZING!!”

CB in Wisconsin writes:

“I have suffered from chronic diarrhea for the past ten

years. By the third day taking Sweetamine I began to see a

100% improvement and now have regular bowel move-

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 The Glycine Miracle
ments. I also had a pain that ran down my right leg that

has decreased considerably. I love your product!”

Mary, in Ridgefield, Washington, writes:

“I have been taking Sweetamine for almost two

months. I had suffered from Irritable Bowel Syndrome

(IBS) and Sweetamine calmed my intestinal tract. I also

found relief from a bad shoulder that I couldn’t lift above

my head without pain and even had discomfort driving.

Now it is almost 100% No pain!”

FM in Gilbert, Arizona, writes:

“I am thrilled with Sweetamine! I have suffered from

colitis and diverticulitis for years. I have been using Swee-

tamine for 4 months, the pain is gone. I have regular

healthy bowel movements now. The yeasty film that used

to be on my tongue which I tried to get rid of for years is

now gone! I have clear whites in my eyes which used to be

cloudy. The arthritis in my knees is much less, too.”

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 The Glycine Miracle
c) Other diseases.
Notice how all of these people who found relief from
inflammatory bowel conditions also experienced relief
from bodily aches and pains related to arthritis. When
glycine is deficient (evidenced here by the correction of
the condition with glycine supplementation), inflamma-
tion is often systemic, and shows up in all sorts of places.
The last testimonial above also referenced improvement
in the eyes, and the eyes are also where a host of inflam-
matory processes show up as disease, for example, in age-
related macular degeneration (AMD).

Lucien, in Lincoln, Rhode Island, writes:

“I’m diabetic type 2 and I’ve been using Sweetamine

for about a year, and this stuff WORKS! I have diabetic

neuropathy from my knees down and severe macular de-

generation (AMD). I’ve been taking Lyrica and Avastin

for those conditions. But with Sweetamine, my doctor was

able to lower the dosage of both of them and I feel a lot bet-

ter. Sweetamine takes the feeling of severe tightness out of

the neuropathy. It really works!”

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 The Glycine Miracle
Here again, note the presence of inflammation-related
comorbidity, specifically type 2 diabetes and diabetic neu-
ropathy. Note also the powerful prescription drugs: Lyrica
(pregabalin) is a potent drug for nerve pain. According to
the Cleveland Clinic, it “works by calming overactive
nerves in your body.” That kind of sounds like what glycine
does, as one of the body’s natural inhibitory neurotrans-
mitters, doesn’t it? Avastin (bevacizumab), is one of the ex-
pensive, semi-synthetic “mab” drugs (monoclonal
antibodies) that need to be taken by injection. It is pre-
scribed for AMD for the same purpose as it is prescribed
for the treatment of several types of cancer, specifically, to
inhibit the growth of blood vessels, thus inhibiting the
growth of cancerous tumors, and also the overgrowth of
blood vessels in the retina which is part of the AMD dis-
ease process.
Hence, this drug is known as an anti-angiogenic drug.
And even though angiogenesis is not an inflammatory
process, it is actually inhibited by glycine. Endothelial
cells—the cells that line the blood vessels—are equipped
with the same glycine receptors that are found in
macrophages and neurons. First described in 2001 by the
Thurman group at UNC, Mark McCarty of Natural Alter-
natives International in San Marcos, CA—a rare glycine

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 The Glycine Miracle
supplementation enthusiast—suggested exploiting this
fact for preventing or treating cardiovascular disease back
in 2009.

150
 Chapter Eleven
Genetic Disorders Affecting
or Affected by Glycine
There are a number of rare genetic defects that affect
glycine synthesis or metabolism, as well as some that cause
disease without affecting glycine directly, but the severity
of which may be affected by the usual state of glycine de-
ficiency. We have already seen, from the work of Hartiala
et al. at the Cleveland Clinic, that a genetic defect in the
synthesis of urea (CPS-1 deficiency), which is largely made
from glycine, results in higher levels of glycine and a lower
incidence of heart attack in women who have this genetic
defect. (This type of benefit due to having one copy of a
defective gene is well known in sickle cell anemia/sickle
cell trait, wherein having one copy of a defective hemoglo-
bin synthesis gene confers resistance to malaria. Such
genes are called pleiotropic genes.)

Nonketotic hyperglycinemia
Another genetic defect in glycine metabolism which is
usually fatal (if the defect is complete) in the early years of
life is called non-ketotic hyperglycinemia, or NKH. This
involves a defect in the gene that codes for what is known

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 The Glycine Miracle
as the glycine cleavage system, which is the main route of
glycine metabolism. It is basically a neurological disorder,
because glycine cleavage is critical within the neurons of
the central nervous system, where glycine serves as a neu-
rotransmitter. (Treatment strategies for NKH generally in-
volve feeding with substances such as benzoic acid, which
binds to glycine and helps to clear it through the urine.)
In particular, the toxicity of the excess glycine is to the
NMDA receptor, for which glycine acts as a co-activator
(as opposed to the glycine receptor, by which glycine acts
as an inhibitory neurotransmitter). Curiously, this illness
does not show up until after birth. I also find it curious
that the steroid DHEA (a natural product of the adrenal
gland, and which is available over-the-counter as a supple-
ment) is found to be protective of NMDA receptors in
other contexts, and DHEA concentration is normally very
high prenatally (as it is made then by the feto-placental
unit), but drops abruptly to zero right after birth. DHEA
is a precursor to the sex hormones estrogen and testos-
terone, but is inactive on its own. (Moreover, there are now
synthetic derivatives of DHEA available, such as BNN27,
which cannot be converted to sex hormones.) DHEA nat-
urally starts to rise at about age eight (an event called
adrenarche, a precursor to puberty), and it can naturally

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 The Glycine Miracle
reach very high concentrations. Hence I hypothesize that
in individuals with NKH, the NMDA receptor is naturally
protected by DHEA before birth, such that prenatal brain
development is normal. Therefore, I would suggest that
supplementing with DHEA after birth might prevent the
disease process of NKH from manifesting.
Since we have now veered off the subject of glycine de-
ficiency per se, let us now extend our excursion a bit to
discuss two interesting examples of heritable (genetic) dis-
eases that have nothing at all to do with glycine, but for
which glycine supplementation may offer a good treat-
ment option. Importantly, I am not suggesting using
glycine as a therapeutic drug; rather, as a nutrient which
is normally deficient in the diet which can therefore be
normalized by supplementation. I would even be so bold
as to suggest that there are certain genetic diseases which
are not really genetic diseases, but genetic variants which
will only produce disease—or serious disease—in the pres-
ence of glycine deficiency.

Hereditary Hemorrhagic Telangiectasia

HHT is a genetic disorder that has long (since the mid-
19th Century) been known as a hereditary bleeding disor-
der, similar to the various types of hemophilia. However,

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 The Glycine Miracle
it is now known that the genetic defects (there are several
variants) produce an oversecretion of the natural chemical
mediator (like a hormone, but acting locally) called vascu-
lar endothelial growth factor or VEGF (discovered in
1989). What excess VEGF does is produce overgrowth of
capillaries at various places in the body, which are then
prone to bleeding. Nosebleeds are the most common
symptom, but bleeding can occur anywhere in the body,
such as in the intestines, and blood loss, anemia and heart
failure can result from this very serious condition. It may
afflict over one million people worldwide, and I just
searched and found no less than 175 review papers on
HHT: a very substantial literature devoted to the diagnosis
and treatment of it. Most of the treatment protocols cen-
ter on countering the proliferative effects of VEGF, i.e.,
through the use of anti-angiogenic drugs. Recall from the
previous chapter that anti-angiogenic drugs are part of the
medical armamentarium against cancer, for they inhibit
tumor growth by inhibiting the ability of the tumor to
grow a blood supply. Recall also that the cells of the en-
dothelium—the cells which line the interior walls of the
blood vessels and which constitute target tissue for
VEGF—are also equipped with glycine receptors. This has
been known since at least 2001, and recall that McCarty

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 The Glycine Miracle
even suggested that the resulting anti-angiogenic action of
glycine could be exploited for the treatment of cardiovas-
cular disease back in 2009. Yet, for all the massive research
dedicated to the treatment of HHT, not even one sugges-
tion of the use of glycine in HHT has been proposed!
When we consider the fact that most people are glycine
deficient, the question that arises to me is: Would this ab-
normality even produce disease among people who had
truly healthy levels of glycine? It would certainly do no
harm to try glycine supplementation in those suffering
from HHT.

Cystic fibrosis
Unlike HHT or NKH, CF is a genetic disorder which
is well known to the general public, afflicting some 89,000
people worldwide. With a tremendous focus of the med-
ical and medical research community, mean survival of CF
has risen over recent years to about 53 years of age. CF
arises from one of several genetic defects in the gene for a
cell membrane protein called CFTR (Cystic Fibrosis
Transmembrane conductance Regulator). CF is a debilitat-
ing disease, the worst manifestation being difficulty
breathing due to inflammation in the airways and lungs. It
has attracted my attention because CFTR is a chloride ion

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 The Glycine Miracle
channel—just like the glycine receptor. Hence, it seems to
me that raising glycine concentration to a truly healthy
level, by glycine supplementation, might be able to aug-
ment the balancing of chloride ions via the glycine recep-
tor, even perhaps normalizing the condition. In other
words, as I suggested earlier for HHT, CF might also con-
stitute a group of genetic variants which only produce dis-
ease—or serious disease—in the presence of a glycine
deficiency. Yet, a review of CF in the prestigious Journal
of the American Medical Association (JAMA) just pub-
lished in 2023 makes no mention of this possibility, even
though a 2017 clinical trial of glycine supplementation ob-
tained substantial benefits in the trial patients. The 2017
randomized, placebo controlled crossover trial (Glycine-
treated and placebo-treated patients switched places after
eight weeks.) was conducted by the Vargas group in Mex-
ico City, who supplemented patients (13 children aged 6-
18) with 0.5 g/kg body weight/day.
The Vargas study was undertaken to test glycine as anti-
inflammatory therapy, considering the known, anti-inflam-
matory effects of glycine, and as a bronchial muscle relaxant,
since bronchial muscles are known to possess glycine recep-
tors which induce relaxation. The subjects improved on
glycine therapy, both in terms of respiratory function and

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 The Glycine Miracle
the concentration of inflammatory markers in the patients’
serum and sputum. The Vargas team concluded, “Thus, if
replicated, our results suggest that glycine might constitute
a novel therapeutic tool in patients with CF.”
Appropriately, they also acknowledged that, “Larger
and longer-term clinical trials, perhaps without a cross-
over design, are needed to corroborate our results.” Okay,
that was 2017. Where are the follow-up trials for the treat-
ment of this debilitating, life-shortening terrible disease,
with a natural nutrient that is completely harmless (and
inexpensive)? Such deafening silence has become all too
familiar concerning treatments that are not patentable,
and therefore unlikely to attract substantial investment for
clinical research.

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 Chapter Twelve
Cutting Through TMI
on Chronic Disease
Understanding glycine’s role in regulating inflamma-
tion, and inflammation’s role in causing all manner of
chronic illness, it is easy to conclude that eating more
glycine is all one needs to do to ward off or even reverse
the vast majority diseases that make us sick and die these
days. But then we are also confronted with voluminous re-
search about other factors that appear to be causally im-
portant. What about the gut microbiome and the
importance of probiotics? What about all the colorful
plant pigments and bioflavonoids that seem to have ben-
eficial effects? As I have pointed out repeatedly in this
book, a genuinely scientific approach seeks to find the
simple, central or fundamental causes of disease, rather
than to focus on the complexity. But once a common, fun-
damental factor is identified—glycine—it also behooves
us to determine and to explain how other, seemingly fun-
damental factors fit into the scheme we have elucidated—
or not. Science tells us there is but one truth, and that
everything about the issue that is true should fit into that

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singular scheme. So what about these other factors that
are gaining traction through recent research?

The gut microbiome

More and more attention has been focused recently on
the importance of the trillions of bacteria that normally
inhabit the human gastrointestinal tract. Exactly what sort
of mix of bacteria and what their secreted products do for
us and to us is unarguably important. For many decades
we have known, for example, that Vitamin K, which is es-
sential to human life and health, is not made by the human
body. (That’s why it’s called a vitamin.) Rather, it is made
by gut bacteria, and it is an essential component of the en-
zymatic machinery in the liver that makes several of the
clotting factors in the blood (i.e., Factors II, VII, IX and
X). When we take antibiotics to combat a bacterial infec-
tion, many of the “good bacteria” in the gut are also killed,
leading to a functional deficiency of Vitamin K. That’s why
it is not uncommon for transient bleeding issues, such as
nosebleeds, to occur during or after a course of antibiotic
treatment. However, there is much that is still unknown
and just recently being elucidated about what these gut
bacteria make and how they affect human health.

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Currently there is emerging a sizable literature on the
subject of the metabolite trimethylamine oxide (TMAO),
which is made by gut bacteria from the nutrient choline
(also from related nutrients betaine and carnitine). More
precisely, gut bacteria produce the metabolite trimethy-
lamine, which the liver oxidizes to form TMAO). Muscle
meats are rich in choline so meat-eaters eat a lot of it, and
have lots of gut bacteria that can utilize choline for their
nutrition. At this point, readers with some knowledge of
biochemistry might just be thinking: “Wait a minute! Can’t
choline be turned into glycine? So doesn’t eating more
choline mean eating more glycine?” Yes, but in the same
way that eating more muscle meat also means eating more
glycine, as we saw here in a previous chapter, the net result
is glycine depletion because of meat’s high methionine
content. That’s because choline is rich in methyl groups
(It has three of them), and it uses up a molecule of glycine
to remove each of those methyl groups. In fact, it is re-
moval of those methyl groups that is part of the process
of regenerating methionine when it is in short supply. Get-
ting back to TMAO specifically, it has been specifically
linked to the development of atherosclerosis by many re-
searchers worldwide. How does TMAO cause cardiovas-
cular disease (CVD)? By provoking inflammation in the

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blood vessel walls! Hence it is reasonable to hypothesize
that the primary cause of CVD is a deficiency of glycine,
for this deficiency makes the macrophages prone to initi-
ate inflammation inappropriately.
There is also substantial literature on the effects of the
increased consumption of nitrates and nitrates, inorganic
substances used as preservatives in processed meats. These
substances are metabolized by gut microflora to produce
many nitrosamines, which are known human carcinogens.
Nitrosamines are also generated by consumption of to-
bacco products. But how do they induce cancer? First of
all, the very formation of carcinogenic nitrosamines in the
body is closely tied to inflammation, via the reactive oxi-
dation products of inflammation—Remember, that’s one
way inflammation kills infectious microbes. Hence we can
see the operation of a vicious cycle of inappropriate inflam-
mation, resulting in oxidative damage and oxidative forma-
tion of carcinogens, and thus more inflammation resulting
from the cellular damage, that is, if glycine is deficient.

Other dietary factors and environmental exposures

Here I have mentioned only a few lines of research link-
ing so many different types of dietary and environmental
exposures to the ever-increasing prevalence of chronic dis-

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eases including CVD and cancer. There are also dietary
deficiencies other than glycine—such as Vitamin D and
magnesium—which keep emerging in the research litera-
ture. So how do we make sense of it all? Since I have con-
cluded that, at least in regard to any condition involving
inflammation, “All roads lead to glycine and glycine defi-
ciency,” it behooves me to trace these connections, even
and especially where it does not seem obvious at first. I
will take two very recent examples as cases in point, as this
book is by no means intended to be an exhaustive analysis
of everything linked to the incidence of chronic disease.

Pentadecanoic Acid (PDA)

A particularly exciting discovery over the last two
decades concerns a specific fat molecule called pentade-
cenoic acid (PDA). This is actually a type of saturated fat—
which of course has been a “dirty word” since the 1970s,
with the belief that only the essential polyunsaturated fats
such as EPA (eicosapentaenoic acid) and DHA (docosa-
hexaenoic acid) were healthy to eat. To fill in a few basics
here, most fats are molecules called triglycerides, made up
of fatty acids and glycerin, a small sugar alcohol. Saturated
fatty acids have no double bonds between the carbon
atoms. The double bonds—in strategic places within the

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chain of carbon atoms—confer rigidity, and thus, confer
specific stable shapes to the molecule. As fatty acids are a
major component of cellular membranes—which are like
highly specialized soap films—the proper function of the
membranes requires a particular mix of types of fatty
acids, in terms of carbon chain length and the presence of
double bonds at specific places. Almost all fatty acids con-
sist of an even number of carbon atoms, but a small per-
centage of them have odd numbers of carbon atoms, one
of which is pentadecanoic acid (PDA), which has 15.
The study of PDA has been pioneered by veterinary
epidemiologist Stephanie Venn-Watson, co-founder and
CEO of Epitracker, a San Diego based natural pharmaceu-
tical research company. Venn-Watson discovered, using
metabolomics, that PDA was essential to the health and
well-being of dolphins, which she was researching for the
US Navy. Over the last few years, Venn-Watson has estab-
lished PDA (aka C15:0) as an essential fatty acid, which,
like glycine, is made in the human body, but in insufficient
quantities. How does it work? The most important role of
PDA is to make cell membranes in general more stable,
i.e., less vulnerable to stresses such as oxidative damage.
Hence, PDA deficiency leads to an increase in ferropto-
sis—the kind of explosive, pro-inflammatory cell death we

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discussed earlier, similar to the pyroptosis of macrophages
as the final “nuclear detonation” of inflammation. In terms
of disease manifestations, PDA deficiency syndrome—
which Venn-Watson calls ”Cellular Fragility Syndrome,”
“can increase susceptibilities to ferroptosis, dysmetabolic
iron overload syndrome, type 2 diabetes, cardiovascular
disease, and NAFLD.” Sound familiar? This is basically the
panoply of diseases rooted in chronic inflammation, which
I attribute to glycine deficiency!
Furthermore, Venn-Watson also has shown “that C15:0
supplementation can reverse the described C15:0 defi-
ciency syndrome.” Just like glycine supplementation can
reverse the chronic inflammation that results from glycine
deficiency.
Okay, so which is it? Is glycine deficiency the real root
of inflammation-related chronic disease, or is it PDA de-
ficiency? Clearly, as both of these are now shown to be es-
sential nutrients which are causally related to chronic
inflammation and the chronic illnesses that result, which
one is more important? To answer this question, we can
examine the typical diet and dietary sources of both of
these nutrients. Venn-Watson estimates that about one
third of the US population is PDA-deficient, whereas I
would estimate that glycine deficiency afflicts close to

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100% of the population; basically, everyone except bone-
broth enthusiasts (i.e., to the tune of about 8 oz or 250mL
of bone broth daily) and those taking glycine or gelatin
supplements (to the tune of several grams/day of glycine).
Importantly, the best dietary sources of PDA are whole
milk and full-fat dairy products, and meat, fish and poultry.
But that would be the kind of diet that was typical two
generations ago, before meat and dairy foods became
largely low fat or fat-free, and/or low-cholesterol; in other
words, before the food industry began removing most or
all of the PDA from foods. And yet, the removal of satu-
rated fats and cholesterol from food products was spurred
by research showing the typical American ‘meat and pota-
toes’ diet was somehow producing large increases in the
incidence of CVD and cancer, starting in the 1940s, when
almost nobody in the US was PDA-deficient. More impor-
tantly, the putative mechanism by which cellular fragility
from PDA deficiency leads to chronic inflammation, by
causing excess cell death and therefore, inflammation, is
straightforward. As we have seen, cellular death does not
cause inflammation except when glycine is deficient. Re-
member also in our discussion of the causation of insulin
resistance and diabetes, we looked at the fragility of larger
and larger adipocytes (fat cells) as drivers of inflammation.

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Why are these adipocytes so fragile, and therefore
causes of cell death and inflammation? It may well be that
this fragility is what makes obesity the main apparent
cause of insulin resistance and diabetes, and that it is PDA
deficiency that causes the fragility. Hence, I would not be
surprised to see research popping up that shows that over-
weight diabetics might see some reversal of the diabetes
upon supplementation with PDA. Moreover, cellular
fragility of the macrophages themselves clearly makes
glycine deficiency more critical, because glycine protects
by virtue of allowing the influx of chloride ions to combat
the deterioration of the membrane voltage, a process
which will be exacerbated by PDA deficiency.

Magnesium
As I write now in 2024, one of the latest crazes in the
nutritional field is magnesium, and the detrimental health
effects of magnesium deficiency. Like all other minerals
the body needs for normal function, magnesium is essen-
tial: you have to take it in the diet because your body can-
not make any minerals. One of the main dietary sources
cited is green leafy vegetables. Actually, this source is the
most obvious because, in exactly the same way as iron
makes blood and red meat red, it is magnesium that makes

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green plants green. Hence, a healthy diet with lots of green
vegetables contains plenty of magnesium, but with many
people not eating healthy diets, it is estimated that 15% of
the US population is magnesium deficient.
In the body, magnesium—like many other metals, in-
cluding copper and zinc—functions as a working part of
dozens of enzymes; you might call them “nano-machines”
that catalyze (facilitate) biochemical reactions. Therefore,
if the body is deficient, nothing really works right. Not
surprisingly, therefore, lack of magnesium is tied to all
manner of chronic disease. It has also been linked to aging,
because the protection of DNA appears to be one of its
functions.
In terms of supplementation, most recommended are
organically chelated magnesium supplements; that is, mag-
nesium bound to an organic acid, like citric acid, because
such chelates, as they are called, are more readily absorbed
than a mineral form such as magnesium oxide. In fact
there are now currently running competing prime time tel-
evision ads for a magnesium supplement, specifically mag-
nesium glycinate, from two different supplement
manufacturers, Nature Made® and Qunol®. Wow, this
stuff must be pretty good to see such big ad campaigns for
one particular supplement among the many that these two

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companies sell! As I said earlier, magnesium is one of the
latest nutritional crazes. But why, in particular, magnesium
glycinate? As you might guess by its name, it is glycine that
is the organic acid that is chelated to the magnesium in this
supplement. (Glycine is both an organic acid and an organic
base, like all the amino acids.) But in particular, in order to
chelate the magnesium to glycine, it takes two molecules
of glycine for each atom of magnesium, a very light metal
(That’s why it’s more formally called “magnesium bisglyci-
nate”). In fact each molecular complex of magnesium gly-
cinate is actually 85% glycine! That’s why it takes two large
capsules to get 200 mg (Nature Made ® ) or 300 mg
(Qunol® ) of magnesium: each daily serving actually con-
tains 200 or 300 mg of magnesium and 1,333 mg or 2,000
mg (2 grams) of glycine! That is not enough glycine to com-
pletely correct the usual glycine deficiency, as most people
need about eight grams of glycine per day. But it is enough
for most glycine-deficient people to feel the difference in
terms of decreased levels of inflammation.
Therefore I predict that sales of magnesium glycinate
will grow very well in the next few months and years. And
maybe; just maybe, some researchers studying magnesium
supplementation will find much more dramatic health
benefits with magnesium glycinate than with any other

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 The Glycine Miracle
form of magnesium. And maybe the world of medical sci-
ence will come to realize that the real magic nutrient is
glycine after all.
Hence, the real bottom line here is that when it comes
to chronic inflammation and the chronic diseases that re-
sult, many insults, from the oxidative damage caused by
such chemicals as TMAO, to the cellular fragility caused
by PDA deficiency, actually do play causal roles. But the
very central role of glycine as the primary regulator of in-
flammation always seems to emerge when one examines
the causal chain of events. There are many supplement
products on the market—as well as both prescription and
over-the-counter drugs—which claim to “fight inflamma-
tion,” and they do. But glycine does not fight inflamma-
tion, it just stops inappropriate inflammation by keeping
the master switch from switching on inappropriately. And
as glycine is the way the body does it naturally, there are
no drug side effects, because the natural function of in-
flammation in the face of a real infectious challenge is not
compromised.

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 Chapter Thirteen
The Question of Biological Aging
Not surprisingly, since the inflammation-related
chronic illnesses are associated with advancing age, we
need to ask the question: To what extent are these condi-
tions the result of simply aging? This question cannot be
answered, however, unless we are able to define biological
aging, and that’s not so easy. In fact it has yet to be fully
answered, even though the field of aging research has been
around for decades, with several prominent journals ded-
icated to this issue.
There are basically two schools of thought with respect
to aging that are prominent these days. One postulates
that aging—as evidenced by the gradual deterioration of
cellular functions, especially in the mitochondria (the or-
ganelles which function as cellular power plants)—is the
result of the accumulation of products of oxidative dam-
age. The oxidation of biological fuels, such as sugar and
fat, produces toxic by-products, collectively referred to as
reactive oxygen species (ROS). The chemistry here is very
simple: Oxygen is itself reactive, producing substantial
amounts of energy when it reacts with biological fuels. But
in the process of these biological oxidations, small

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amounts of super-reactive forms of oxygen—called free
radicals—are also produced. These ROS are so reactive
that they cause damage to the normal cellular machinery.
It is widely hypothesized that these damaged molecules
gradually accumulate to the point where they interfere
with normal cellular function, thus producing chronic dis-
ease associated with age.
The human body, however, is designed to chemically
neutralize these ROS, using substances collectively re-
ferred to as antioxidants. One such is the enzyme super-
oxide dismutase. Some small antioxidant molecules are
nutrients, such as Vitamin C, Vitamin E and a host of
“bioflavonoids.” But importantly, the body itself makes an-
tioxidants, the one considered the most important being
glutathione (GSH). There is a substantial school of
thought that implicates low levels of GSH with the aging
process. Chemically, glutathione is what is called a tripep-
tide, that is, it is composed of three amino acids. Proteins,
of course, are large molecules made of many amino acid
molecules; not just three. Glutathione is also different
from proteins in that it is not made by the same process,
but the three amino acids are linked together by the same
type of bond as are the amino acids of proteins, and it can
be broken down into its component amino acids by the

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same enzymes that break down proteins in the digestive
system. The amino acid which is responsible for the an-
tioxidant function of GSH is the sulfur-containing amino
acid called cysteine. But importantly, one of the three
amino acids in GSH is glycine. That means that GSH con-
tains about 25% glycine by weight; about the same per-
centage as collagen. Hence it is a very rich source of
glycine. Therefore it is worth examining whether benefits
attributed to supplementation with GSH may actually be
due to the glycine content of GSH.

A recent (2011-2022) series of studies on both mice and

people by a group of doctors at Baylor Medical College in
Houston, TX provides a good case in point. Focusing on
the importance of GSH in aging and disease, P Kumar and
RV Sekhar and colleagues tested old v young mice as well
as old (in their 70’s) v young men and women and diabetic
v non-diabetic men and women for blood GSH and a host
of clinical parameters, i.e., oxidative stress, mitochondrial
dysfunction, inflammation, insulin resistance (aka “pre-di-
abetes”), endothelial dysfunction (endothelium being the
cellular layer that lines the inner surface of blood vessels),
genotoxicity, muscle strength, and cognition. The experi-
mental groups were all supplemented with both cysteine

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(as N-acetylcysteine) and glycine. Hence the supplemen-
tation protocol was termed GlyNAC. These studies fol-
lowed up on earlier studies on mice, wherein they had
observed negative effects on these functions when GSH
synthesis was suppressed. Importantly, the authors’ ration-
ale was based entirely on glycine and NAC serving as pre-
cursors to GSH. The GlyNAC-supplemented diet
normalized all these clinical parameters. Not surprisingly,
the authors attributed these beneficial results to the nor-
malization of GSH levels, which they observed. Specifi-
cally, they concluded: “The observation that improving
glutathione synthesis and concentrations resulted in a re-
duction in oxidant damage suggests that the primary rea-
son for oxidative stress in aging is glutathione deficiency.”
However, by 2021 the authors acknowledged: “However,
correction of GSH alone is insufficient to explain the mag-
nitude and extent of improvements, suggesting that there
may be other factors in play.” Here, they introduced what
they call “The power of three,” meaning that GlyNAC
supplementation actually accomplished three things: 1)
correction of GSH status 2) addition of glycine, which has
its own biochemical and other benefits and 3) addition of
cysteine, which has its own important biochemical func-
tions. Importantly, the authors do not mention the role of

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glycine in regulating macrophage function, i.e., controlling
the primary step in inflammation.
Essentially, what we have here are two competing hy-
potheses. The Kumar-Sekhar team from Baylor looks at
oxidative damage as the primary mover in age-related and
inflammation-related decline of bodily functions. This
makes sense in that it is well known that reactive oxygen
species (ROS, the causative chemical species that cause
oxidative damage) provoke inflammation. Restoring the
synthesis and maintenance of adequate concentrations of
the body’s main antioxidant, glutathione (GSH) by supple-
menting with its main precursors, glycine and cysteine (as
NAC), restores healthy function. But not quite, so, as
noted above, they need to supplement their hypothesis
with their ill-defined “power of three” argument.
In contrast my hypothesis views the anti-inflammatory
function of glycine as primal. When a healthy glycine level
is attained, inappropriate inflammation is shut off, thereby
stopping the oxidative stress and damage (an intended
consequence of inflammation, as oxidation is a major way
of killing invading microbes), which also decreases the
need for GSH. In other words, it is entirely possible that
the beneficial clinical results obtained by the Baylor group
were attributable to glycine alone. Unfortunately, I can

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find no evidence that the Baylor group experimented with
supplementation of glycine alone, which would have an-
swered the question. In addition, the modern dietary
trend of eating more muscle meats and less bone and con-
nective tissue exacerbates a glycine deficiency, but not a
cysteine deficiency, as muscle meats are relatively rich in
sulfur-containing (cysteine and methionine) amino acids.
So why would cysteine deficiency be a growing trend?
In addition, in their own research, Sekhar et al saw
GlyNAC supplementation increase blood cysteine by 55%,
but glycine by 142%, blood glycine being much more defi-
cient at the start (24% v 55% of controls, respectively).
Moreover, the Sekhar group does not even mention the
possible confounding effect of acetaminophen (e.g.,
Tylenol®) use, which might well be higher among older v
younger individuals. That’s because acetaminophen is well
known to chemically destroy GSH by destroying its cys-
teine component.
But just as glycine alone might explain all the benefits
the Baylor team observed with GlyNAC supplementation,
glycine’s function in regulating inflammation does not ex-
plain all the benefits of glycine. This was evidenced by a
2016 study by the Hayashi group in Japan, which compared
mitochondrial function in cells derived from elderly

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donors v fetal tissue. They observed defects in cellular res-
piration in the mitochondria in the elderly-derived cells,
but no difference in reactive oxygen species. In other
words, the respiratory dysfunction was not due to oxida-
tive damage as the prevailing theory of cellular aging would
have it. Nor was the difference due to any accumulated
damage to mitochondrial DNA. Rather, as the authors ob-
served when doing a genomic analysis of the cells, i.e., an
analysis of what genes were being expressed, they found
that the respiratory defects of the elderly-derived cells cor-
responded to a downregulation (i.e., shutting off, a form
of what is known as epigenetic regulation) of the two
major genes that represent the two most important path-
ways for the synthesis of glycine. The authors then took
the obvious step to test whether the downregulation of
glycine synthesis was responsible for the respiratory
deficit, by adding glycine to the cell culture medium, and
Presto! Mitochondrial respiration was restored to the level
of the young-derived fibroblasts! So here we observe an-
other direct function of glycine in restoring youthful func-
tion, but having nothing to do with macrophages or
inflammation or the glycine receptor which does not exist
in these cells. So the bottom line is that glycine alone can
explain the difference between elderly and youthful bodily

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function, but in more ways than we yet know!
In fact, there is another major function of glycine in
relation to cellular injury and disease, independent of its
action in regulating inflammation via the glycine receptor,
that has been recognized for almost 4 decades. Getting
back to research on Glutathione (GSH), it was known not
only to guard against reactive oxygen species, but also to
prevent cellular injury, necrosis and death. This is a big
problem when it comes to organ transplants. When a kid-
ney, for example, is removed from a donor for transplan-
tation, the microscopic tubules of the kidney that filter
the blood are very sensitive to damage from a lack of oxy-
gen. The cells that form the part of the kidney nephron
(nephrons being the multicellular working units of the kid-
ney) called the proximal tubules, usually enjoy being
bathed in oxygen-rich blood. Hence, they lack the bio-
chemical machinery to generate energy and stay alive and
functioning even temporarily without oxygen. However, it
was found that adding GSH protects the tubules from
necrosis, not by preventing inflammation, but by some un-
known mechanism.
Harking back to 1987 (and to Chapter Three of this
book), the Weinberg group at the University of Michigan
ran experiments with GSH and its three component

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amino acids, glycine, glutamate and cysteine. The proximal
tubular cells of their laboratory model system (using rabbit
kidneys) were protected from hypoxic injury, but to their
surprise, the cells were also completely protected by
adding glycine alone. Importantly, neither glutamate nor
cysteine alone were protective. Furthermore, they ob-
served that the GSH was hydrolyzed (broken down) rap-
idly upon addition, into the three component amino acids,
suggesting that intact GSH was not the active protective
substance. Finally, they observed that oxidized GSH, in
which the active antioxidant part of the GSH molecule,
cysteine, was inactivated, was just as protective as active
GSH. In other words, Weinberg et al had demonstrated
that it is glycine, and glycine alone that protects against
cell damage and death!
These findings essentially nullify the hypothesis of
Kumar and Sekhar, which would require the presence of
both glycine and cysteine (and in fact, intact GSH) to pro-
tect cells from oxidative damage and death.
But at least they are beginning to focus more on in-
flammation as the main driver of chronic disease.
In my own studies with the Orentreich Foundation on
rats (2011) and with the National Institute on Aging (one
of the NIH institutes) on mice (2019), supplemental

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glycine feeding was found to significantly extend lifespan.
Finally, in their comprehensive review of studies con-
cerning the role of glycine in cell injury and death, published
in 2016, Weinberg and colleagues observed: “Although
glycine is considered a nonessential amino acid, its availabil-
ity may, in fact, be limiting for all of its normal metabolic
roles. Manipulating glycine levels in vivo to potentially elicit
protective effects is feasible because circulating glycine lev-
els in multiple species, including humans and rodents, are
at or below the EC50s (0.5–0.75 mM) required for both its
cytoprotective and anti-inflammatory effects. Serum glycine
levels can be readily increased by either oral feeding or par-
enteral administration, and maximal cytoprotection is seen
at 2–5 mM concentrations that are well below the 16–36 mM
levels associated with acute toxicity.”
Is this not really saying that the general population
may be suffering from glycine deficiency, which is easily
corrected by simply eating more glycine?

Inflammaging
Over the last decade or so, a new paradigm on aging
has been in ascendance, one which is based on the obser-
vations of increased inflammation associated with age. The
chronic low-grade inflammation has even spawned the new

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term “inflammaging.” Indeed, literally hundreds of peer re-
viewed articles on inflammaging have appeared over the last sev-
eral years, and the host of chronic diseases characterized by
chronic inflammation and associated with age are often called
ARDs (age-related diseases, e.g., type 2 diabetes, cardiovascular
disease and cancer).
In addition to the fact that “inflammaging” researchers
seem unaware of the key role of glycine in regulating inflamma-
tion, they typically make an arbitrary distinction between acute
and chronic inflammation. They typically frame the issue of in-
flammation thus: “Inflammation is the body’s natural first re-
sponse to injury or infection. That’s a good thing, but what’s not
good is when the inflammatory reaction becomes chronic, so it
causes progressive damage to normal bodily tissues and func-
tions.” Hence, researchers dwell on the question: “What is it
that makes inflammation become chronic, i.e., that prevents in-
flammation from naturally shutting off after its job is done?”
The real problem is that this is the wrong question! The
problem is not acute v chronic inflammation, but appropriate v
inappropriate inflammation. As we have seen, inflammation is
never an appropriate response to sterile injury for it just does
damage to normal tissues. And even when invading microbes
are present, inflammation may be excessive, even to the point
of causing death rapidly, as it can in Covid pneumonia.

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Therefore “inflammaging” will not likely persist for long as
a descriptor, in my opinion, for it conflates aging with a partic-
ular immune function, thus obscuring the actual fact of aging.
After all, aging happens, even in the absence of inappropriate
inflammation: Nobody lives forever. Yes, inflammation exacer-
bates the deterioration of the body and bodily functions that
are associated with age. And this association is not just happen-
stance. Since the body’s production of glycine slows with ad-
vancing age, chronic inflammation increases with advancing
age. But in order to understand the process of aging per se, we
need to distinguish it from the process of inflammation.

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 Chapter Fourteen
Why Glycine?
What makes glycine so fundamental to good health?
Or we might ask, of all the essential molecules out there,
why is it glycine, in particular, which is so important to
cellular function, especially immune cell function? In a
way, the answer has always been obvious. In fact, the crit-
ical importance of glycine has always been obvious to sci-
entists investigating the origin of life itself. To them, the
question was: What was the source of the organic mole-
cules in the early earth before life arose on this planet that
enabled organic living things to emerge?
Speculation as to the extraterrestrial origin of the or-
ganic molecules essential for life to exist on earth was long
fueled by the discovery of amino acids—including
glycine—in meteorites. However, the possibility that these
organic compounds arose through chemical reactions here
on earth after the meteorites crashed could never be ruled
out. In particular, the identification of glycine was a
sought-after prize because glycine is the simplest of the
amino acids actually used to make proteins. Therefore,
glycine was the key “missing link” between inorganic
chemistry (anywhere in the universe as well as here on

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 The Glycine Miracle
earth) and the biochemistry of living organisms. Glycine
is also the most abundant amino acid in the body and par-
ticipates in more key biochemical reactions than any other
organic compound in the body.
But technological advances more recently have enabled
the actual collection of material from the tail of a comet.
This was the main objective of the Stardust Mission,
launched back in 1999 by the US National Aeronautics and
Space Administration (NASA). In 2004 the spacecraft
conducted a “flyby” of the comet Wild-2, when it collected
dust from the comet’s tail. In 2006, the spacecraft re-
turned to earth and safely landed in the Utah desert.
Analysis of the collected “stardust” revealed a host of or-
ganic molecules—including glycine.
Nevertheless, chemical changes occurring during the
return of the spacecraft could not be ruled out. Efforts to
identify glycine spectroscopically in interstellar clouds and
comet tails from earthbound detectors came up negative,
however, as the chemical nature of glycine makes it very
rare in the gaseous state, which is necessary for spec-
troscopy. At least, it was not until the Rosetta orbiter,
which had been launched by the European Space Agency
(ESA) in 2004, became the first spacecraft to actually orbit
a comet, in this case, Comet Churyumov–Gerasimenko, in

183
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2014. Finally, in 2014 the ROSINA spectrometer aboard
the Rosetta orbiter was able to actually and unequivocally
measure the existence of glycine in the comet’s tail. This
discovery was detailed in a 2016 paper by Kathrin Altwegg
of the University of Bern, Switzerland, and a large interna-
tional group of colleagues, in the prestigious journal Science.
In terms of fundamental building blocks of all living
systems, glycine is about as fundamental as it gets. And as
we have seen, recent research has revealed that glycine is
“the alpha and the omega” of inflammation, that immune
system process which is so dysregulated in the population
as to be responsible for most of the diseases that make
people sick and die these days. That is, glycine regulates
both the initial activation of macrophages to start the in-
flammatory process, and the final cell membrane rupture
of pyroptosis, when a macrophage “goes nuclear.”
As for me, I still hold to the belief that the esteemed
institutions of science and medicine, will eventually
emerge from their current confusion of complexity and re-
alize how the biggest biochemical secret to health and
longevity turns out to be among the very simplest of bio-
chemicals, hidden, as it were, in plain sight.

184
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