THE ART OF

METHYLATION IN
MENTAL HEALTH
Bridget Briggs, MD, ABIHM

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 Legal Disclaimer
The contents of this document are provided for informational
purposes only, to scientists, health care professionals, and
academics. Neither the statements in this document nor
statements made by the presenter should be interpreted as
providing medical advice, a physician-to-physician consultation,
professional diagnosis, a medical or health-related opinion,
treatment, or services to you or any other individual; nor should
they be interpreted as recommending any product, therapy, or
course of treatment. Health care professionals are responsible for
their own independent treatment decisions relative to their
patients. Not responsible or liable for any advice, course of
treatment, or diagnosis made by a health care professional, nor for
any course of action taken by an individual.
The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
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 Participants Will

• Understand the crucial importance of methylation

for mental health.
• Recall three supplements that can enhance
methylation.
• Be able to describe how impairments in
methylation can create psychiatric illness.

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
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 Depression in America

1 in 10

The diagnosis is INCREASING 20% per year

80% of depressed persons do not seek

treatment

“Compared to men, women are twice as likely

to develop depression”
• Psychology Today: The 7 Reasons Why Depression is More Common in Women Compared to men, women are twice as likely to develop depression. Published on May 17, 2012
by Neel Burton, M.D. in Hide and Seek,
• http://www.psychologytoday.com/blog/hide-and-seek/201205/the-7-reasons-why-depression-is-more-common-in-women as reported 30, Sept, 2014
• Healthline Infographic:Posted as of 29/Feb/2016: http://www.healthline.com/health/depression/statistics-infographic
The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Common Interventions for Depression

Reuptake
Reuptake
inhibitors:
inhibitors: Cyclics Atypical
Norepinephrine,
Serotonin
Dopamine

Sertraline Ariprazole
Bupropion Trazodone

Citalopram Olanzapine

Venlafaxine Mirtazapine
Escitalopram Quetiapine

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
Let’s Look at Genetics

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physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
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 Single Nucleotide Polymorphisms (SNPs)

• Most frequent type of mutation in the human

genome.
• A SNP occurs when a nucleotide at a specific
position in the DNA sequence gets replaced with
a different nucleotide.

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
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 Common SNPs with Mood Disorders

MTHFR MAOA MAOB

COMT VDR CBS

• Gilbody S, Lewis S, Lightfoot T. Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms and psychiatric disorders: a HuGE review.Am J Epidemiol. 2007 Jan 1;165(1):1-
13. Epub 2006 Oct 30. [PMID: 17074966]
• Wichers M, Aguilera M, Kenis G, et al. "The catechol-O-methyl transferase Val158Met polymorphism and experience of reward in the flow of daily life". Neuropsychopharmacology 2008.
33 (13): 3030-6. PMID 17687265
• Dlugos AM, Palmer AA, de Wit H. Negative emotionality: monoamine oxidase B gene variants modulate personality traits in healthy humans. J Neural Transm. 2009 Oct;116(10):1323-
34. [PMID: 19657584]
• Denson TF, Dobson-Stone C, Ronay R, et al. A functional polymorphism of the MAOA gene is associated with neural responses to induced anger control. J Cogn Neurosci. 2014
Jul;26(7):1418-27. [PMID: 24564461]
• Beydoun MA, Ding EL, Beydoun HA, Tanaka T, Ferrucci L, Zonderman AB. Vitamin D receptor and megalin gene polymorphisms and their associations with longitudinal cognitive
change in US adults. Am J Clin Nutr. 2012 Jan;95(1):163-78. [PMID: 22170372]
The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Methylation & Depression
“Depressed patients with raised total
plasma homocysteine had significant
lowering of serum, red cell, and CSF
folate, CSF S-adenosylmethionine and
all three CSF monoamine metabolites”
J Neurol Neurosurg Psychiatry 2000;69:228-232 doi:10.1136/jnnp.69.2.228

Clinical note: Restoration of neurotransmitters may require restoration of active methyl donors

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Journal of Clinical & Medical Genomics

“It wasn’t in my head and I wasn’t

depressed. I didn’t need an anti-depressant
or whatever. That’s what everybody kept
trying to give me. I knew there was
something wrong. I wanted an answer, but it
wasn’t (until the MTHFR diagnosis) was
there the answer”

• J Nutrigenet Nutrigenomics. 2015;8(3):137-50. doi: 10.1159/000440700. Epub 2015 Oct 21. Epigenetics in Clinical Practice: Characterizing Patient and
Provider Experiences with MTHFR Polymorphisms and Methylfolate. Oberg E1, Givant C, Fisk B, Parikh C, Bradley R.

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Advances in Psychiatric research
“Recent evidence suggests that some
autistic children may have reduced
detoxification capacity and may be under
chronic oxidative stress. Based on reports of
abnormal methionine and glutathione
metabolism in autistic children, it was of
interest to examine the same metabolic
profile in children”
• J Autism Dev Disord. 2008 Nov;38(10):1976. doi: 10.1007/s10803-008-0614-2. Abnormal Transmethylation/transsulfuration Metabolism and DNA Hypomethylation Among Parents
of Children with Autism. James SJ1, Melnyk S, Jernigan S, Hubanks A, Rose S, Gaylor DW.
• Nutr J. 2008 Jan 21;7:2. doi: 10.1186/1475-2891-7-2. Nutritional therapies for mental disorders. Lakhan SE1, Vieira KF.
• Glob Adv Health Med. 2013 Nov;2(6):68-73. doi: 10.7453/gahmj.2013.087. Autism: a redox/methylation disorder. Deth RC1.
• Am J Hum Genet. 1998 May;62(5):1044-51. A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? van der
Put NM1, Gabreëls F, Stevens EM, Smeitink JA, Trijbels FJ, Eskes TK, van den Heuvel LP, Blom HJ.

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Enzyme Function of Core SNPs
MTHFR • Produces 5-methyltetrahydrofolate (5-MTHF).

MTR • Recycles homocysteine back into methionine. This enzyme is

B12 dependent.

MTRR • Recharges MTR via re-methylation. This enzyme is B12

dependent.

• Catalyzes the conversion of betaine and homocysteine to

BHMT dimethylglycine and methionine. This is one of two
biochemical pathways involved in recycling homocysteine.

• Catalyzes the conversion of homocysteine to cystathionine,

CBS the first step in the transsulfuration pathway which ultimately

involves the degradation of sulfur-containing amino acids. B6
is a cofactor.

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Enzyme Function of Core SNPs
VDR • Vitamin D receptor is involved in mineral metabolism, immune
function and dopamine synthesis.

• Catalyzes phase II detoxification (metabolism) of

COMT neurotransmitters dopamine, epinephrine, and norepinephrine,
as well as estrogen.

MAO-A • Catalyzes the oxidative deamination (inactivation) of amines,

such as tyramine, dopamine, norepinephrine and serotonin.

• Catalyzes the oxidative deamination (inactivation) of biogenic

MAO-B and xenobiotic amines, specifically epinephrine and histamine,
as well as dopamine.

NOS • Encodes for nitric oxide synthases which catalyze the reaction
of oxygen with l-arginine generating citrulline and nitric oxide.

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
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 The Metabolic Pathway Gears
Biopterin

Krebs Folate Methionine

Transsulfuration

Nitric Oxide

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Compromised Gears

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physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Function of Folate Gear

• Its purpose is to convert dietary folate and folic acid from

supplements and fortified foods to the active form, 5-
methyltetrahydrofolate (5-MTHF).
• 5-MTHF provides the substrate for the transmethylation
cycle.

• Kidney International, Vol 59 Suppl 78 (2001) pp221-229. The Folate cycle and disease in humans. Brian Fowler. The effect of multiple single nucleotide polymorphisms in the folic
acid pathway genes on homocysteine metabolism. Liang S1, Zhou Y2, Wang H3, Qian Y4, Ma D4, Tian W 2, Persaud-Sharma V5, Yu C6, Ren Y1, Zhou S5, Li X7.

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Function of Folate Gear
DNA Synthesis & Repair

Neurotransmitter Production

Glutathione Synthesis

Detoxification of Homocysteine

Related gears

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Function of MTHFR
(methyltretahydrofolate)

• MTHFR is the enzyme responsible for the final and

irreversible step of the conversion of folic acid/(5,10MTHF)
into the active form 5-MTHF.

• Proc Natl Acad Sci U S A. 2008 Nov 11;105(45):17573-8. doi: 10.1073/pnas.0803727105. Epub 2008 Nov 6. MTHFR 677C --> T genotype disrupts prefrontal function in schizophrenia
through an interaction with COMT 158Val --> Met. Roffman JL1, Gollub RL, Calhoun VD, Wassink TH, Weiss AP, Ho BC, White T, Clark VP, Fries J, Andreasen NC, Goff DC, Manoach
DS.
The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 MTHFR SNP
Can have a negative impact on:

DNA Synthesis & Repair

Neurotransmitter Production

Glutathione Synthesis

Detoxification of Homocysteine

Related gears
The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Function of MTR (methionine synthase) /MTRR
(methionine synthase reductase) SNPs

Imbalances result from an upregulated enzyme:

• Will drain MB12 to create lower than normal
homocysteine and elevate methionine.
• High dependency on B12 especially MB12 for energy
balance.

• Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3059-64. Cloning and mapping of a cDNA for methionine synthase reductase, a flavoprotein defective in patients with homocystinuria.
Leclerc D1, Wilson A, Dumas R, Gafuik C, Song D, Watkins D, Heng HH, Rommens JM, Scherer SW, Rosenblatt DS, Gravel RA.
• J Nutr. 2004 Nov;134(11):2985-90. Methionine synthase reductase 66A->G polymorphism is associated with increased plasma homocysteine concentration when combined with
the homozygous methylenetetrahydrofolate reductase 677C->T variant. Vaughn JD1, Bailey LB, Shelnutt KP, Dunwoody KM, Maneval DR, Davis SR, Quinlivan EP, Gregory JF 3rd,
Theriaque DW, Kauwell GP.

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Folate Gear - CORE SNPs
MTHFR

• Converts 5,10 methylene-THF into 5-MTHF, the

active form of folate in the body
• SAMe inhibits

MTR

• To synthesize methionine from homocysteine while

using Methyl B12 as the methyl donor

MTRR

• Regenerates Methyl B12 for use by MTR

• SAMe restores the inactivated form

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Folate Gear
Imbalances may lead to these clinical patterns:

Estrogen Depression/
Migraines dominance Anxiety

Cardiac
Fatigue
dysfunction

• Gilbody S, Lewis S, Lightfoot T. Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms and psychiatric disorders: a HuGE review.Am J Epidemiol. 2007 Jan
1;165(1):1-13. Epub 2006 Oct 30. [PMID: 17074966
• Schürks M1, Zee RY, Buring JE, Kurth T.Interrelationships among the MTHFR 677C>T polymorphism, migraine, and cardiovascular disease. Neurology. 2008 Aug
12;71(7):505-13 [PMID: 18672474]
The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Nutritional Cofactors of Folate Gear

• Methyl B12 SL, INJ, Oral

• 5-MTHF SL, Injection, Oral
• B2 oral & component of B Complex
Injection/ oral
• B3 oral & component of B Complex
Injection/ oral

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
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 Importance of B Complex

B2

5,10 MTHF MTHFR 5-MTHF

Enzyme

B3

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Flow of B12:

Cyanocobalamin Methylcobalamin

Adenylcobalamin

Hydroxycobalamin
B5 Acetyl CoA Krebs

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
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 Clinical Observations:
Which B12 for Which Patient?
Majority Methyl Sensitive Others

Certain patients are overstimulated by

Most patients MethylBs (COMT Val158++). May support Adenyl B12 in
prefer Methyl B12 patients with HydroxyB12 shots or drops 2000 fatigue patients
for energy mcg/day & folinic acid 1000 to 2000 mcg/day

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Function of Methionine Gear

• Balances transmethylation
vs. transsulfuration
pathways
• Maintains global methylation
balance (SAMe / SAH)
• Long route is folate
dependent
• Short route, liver only, is
non-folate dependent

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
Function of SAMe

• Primary methyl donor necessary to synthesize:

• Choline
• Creatine
• Co-Q10
• Carnitine
• Melatonin
• Norepinephrine
• Methylates DNA
• Maintains Myelin

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
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 Function of BHMT
(Betaine-homocysteine methyltransferase)

• BHMT re-methylates
homocysteine via the “short
route”
• BHMT pulls homocysteine
away from the
transsulfuration pathway
• Choline/TMG are coenzymes

• The Journal of Nutrition. Recent advances in Nutritional sciences. Kelly T. Williams, Kevin L. Schalinske. Department of Food Science
• Nutrients. 2013 Sep 9;5(9):3481-95. doi: 10.3390/nu5093481. The metabolic burden of methyl donor deficiency with focus on the betaine homocysteine methyltransferase
pathway. Obeid R1
• J Nutr. 2007 Feb;137(2):311-4. New insights into the regulation of methyl group and homocysteine metabolism. Williams KT1, Schalinske KL.
The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 BHMT SNP

Cause the “short route” to slow down in

the liver which may impair phase II
detoxification

Push the “long route” and may up-

regulate the transsulfuration pathway

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Methionine Gear
Imbalances may lead to these clinical patterns:

High
IBS / SIBO
homocysteine

Fatigue

• Harmon DL, Shields DC, Woodside JV, et al. Methionine synthase D919G polymorphism is a significant but modest determinant of circulating homocysteine concentrations. Genet
Epidemiol. 1999 Nov;17(4):298-309. [PMID: 10520212]
• Laraqui A, Allami A, Carrié A, et al. Influence of methionine synthase (A2756G) and methionine synthase reductase (A66G) polymorphisms on plasma homocysteine levels and
relation to risk of coronary artery disease. Acta Cardiol. 2006 Feb;61(1):51-61. [PMID: 16485733]

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Nutritional Cofactors of Methionine Gear

• Methyl B12
• 5-MTHF
• Zinc
• Betaine/TMG
• Choline

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
Interplay of Folate & Methionine Gears

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Function of Transsulfuration

• Synthesis of:
• Glutathione
• Sulfate Groups
• Metalothionine
• Bile acids
• Detoxification
• Hormones
• Catecholamines
• Cholesterol

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Function of CBS (Cystathionine beta-synthase)

• B6 & zinc dependent

enzyme
• Activates transsulfuration
pathway
• Produces sulfur containing
amino acids

• Williams KT, Schalinske KL. New insights into the regulation of methyl group and homocysteine metabolism. J Nutr. 2007 Feb;137(2):311-4. PubMed PMID: 17237303.
• Am J Physiol Heart Circ Physiol. 2010 Nov;299(5):H1568-76. doi: 10.1152/ajpheart.00555.2010. Epub 2010 Sep 3. Extracellular transsulfuration generates hydrogen sulfide from
homocysteine and protects endothelium from redox stress. Bearden SE1, Beard RS Jr, Pfau JC.
The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 CBS SNP

C699T polymorphism in CBS results in an up-

regulation causing the enzyme to work too fast.

Increased activity causes rapid conversion of

homocysteine and cystathionine into taurine and
ammonia.

Up-regulation of CBS increases downstream

metabolites and may result in sulfur intolerance in
some patients.

• Nutrition. 2010 Nov-Dec;26(11-12):1170-5. doi: 10.1016/j.nut.2009.10.006. Epub 2009 Dec 29. Methionine-deficient diet induces post-transcriptional downregulation of
cystathionine β-synthase. Tang B1, Mustafa A, Gupta S, Melnyk S, James SJ, Kruger WD.
• Cell Stress and Chaperones (2013) 18:631-641 Inhibition of cystathionine B- synthase is associated with glucocorticoids over-secretion in psychological stress-induced
hyperhomocystinemia rat liver. Yun Zhao. Shuqing Wu. Xiujie Gao. Zhiqing Zhang. Jingbo Gong. Rui Zhan. Xinxing Wang. Weiming Wang. Lingjia Qian.
The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
CBS SNP

• B6 and SAMe can produce excess:

• Sulfites
• Sulfur containing amino acids
• Ammonia
• Bile acids
• Histaminergic

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Transsulfuration
Imbalances may lead to these clinical patterns:

IBS / SIBO GERD

Joint / tendon Poor digestion /

pain detoxification

• Williams KT, Schalinske KL. New insights into the regulation of methyl group and homocysteine metabolism. J Nutr. 2007 Feb;137(2):311-4. PubMed PMID: 17237303.
• Am J Physiol Heart Circ Physiol. 2010 Nov;299(5):H1568-76. doi: 10.1152/ajpheart.00555.2010. Epub 2010 Sep 3. Extracellular transsulfuration generates hydrogen sulfide
from homocysteine and protects endothelium from redox stress. Bearden SE1, Beard RS Jr, Pfau JC.
The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
Nutritional Cofactors of Transsulfuration

• P5P/B6
• Manganese
• Molybdenum
• Serine
• SAMe

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Function of Biopterin Gear

• Key pathway related to:

• Neurotransmitter synthesis
• Nitric oxide synthesis
• Clearance of ammonia

• Folate gear dependent

• Arch Dis Child. 1986 Feb;61(2):130-7. Neurological aspects of biopterin metabolism. Smith I, Leeming RJ, Cavanagh NP, Hyland K. Antioxid Redox Signal. 2014 Jun
20;20(18):3040-77. doi: 10.1089/ars.2013.5566. Epub 2014 Mar 14. Tetrahydrobiopterin in cardiovascular health and disease. Bendall JK1, Douglas G, McNeill E, Channon
KM, Crabtree MJ.
• Psychiatr Danub. 2015 Mar;27(1):25-30. Urinary neopterine levels in patients with major depressive disorder: alterations after treatment with paroxetine and comparison with
healthy controls. Taymur I1, Özdel K, Özen NE, Güngör BB, Atmaca M.
The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Enzyme Function
MAO-A
• Catalyzes the oxidative deamination (inactivation) of amines, such as
tyramine, dopamine, norepinephrine and serotonin.

MAO-B
• Catalyzes the oxidative deamination (inactivation) of biogenic and
xenobiotic amines, specifically epinephrine and histamine, as well as
dopamine.

• BMC Genet. 2005 Sep 20;6:46. MAOA haplotypes associated with thrombocyte-MAO activity. Jansson M1, McCarthy S, Sullivan PF, Dickman P, Andersson B, Oreland L, Schalling
M, Pedersen NL.
• J Psychiatry Neurosci. 1993 Jan;18(1):25-32. Structure and promoter organization of the human monoamine oxidase A and B genes. Shih JC1, Grimsby J, Chen K, Zhu QS.
The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 MAO-A (Monoamine oxidase A) SNP
Males only have one allele since the gene is inherited from
their mother and located on the X chromosome

The rs 6323 SNP affects MAO-A enzymatic activity and

can result in higher or lower neurotransmitter levels,
depending on SNP combinations (haplotypes).

When MAO-A SNP’s are combined with COMT SNPs

imbalances in neurotransmitters may be more severe

• Neuropsychopharmacology. 2005 Sep;30(9):1719-23. Association study of a monoamine oxidase a gene promoter polymorphism with major depressive disorder and
antidepressant response. Yu YW1, Tsai SJ, Hong CJ, Chen TJ, Chen MC, Yang CW.
• Hum Mol Genet. 1999 Apr;8(4):621-4. Excess of high activity monoamine oxidase A gene promoter alleles in female patients with panic disorder. Deckert J1, Catalano M, Syagailo
YV, Bosi M, Okladnova O, Di Bella D, Nöthen MM, Maffei P, Franke P, Fritze J, Maier W, Propping P, Beckmann H, Bellodi L, Lesch KP.
• Biol Psychol. 2011 Jul;87(3):366-71. doi: 10.1016/j.biopsycho.2011.04.007. Epub 2011 May 7. Gene environment interactions with a novel variable Monoamine Oxidase A
transcriptional enhancer are associated with antisocial personality disorder. Philibert RA1, Wernett P, Plume J, Packer H, Brody GH, Beach SR.
• Am J Hum Genet. 1991 Aug;49(2):383-92. Human monoamine oxidase A gene determines levels of enzyme activity. Hotamisligil GS1, Breakefield XO.
The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 MAO-B (Monoamine oxidase B) SNP

Males only have one allele since the gene is

inherited from their mother and located on the X
chromosome.

Since MAO-B preferentially metabolizes

dopamine, SNP’s in MAO-B are associated with
altered dopamine levels.

• Proc Natl Acad Sci U S A. 1991 May 1;88(9):3637-41. Human monoamine oxidase A and B genes exhibit identical exon-intron organization. Grimsby J1, Chen K, Wang LJ, Lan
NC, Shih JC.
• J Neural Transm (Vienna). 2009 Oct;116(10):1323-34. doi: 10.1007/s00702-009-0281-2. Epub 2009 Aug 6. Negative emotionality: monoamine oxidase B gene variants modulate
personality traits in healthy humans. Dlugos AM1, Palmer AA, de Wit H.
The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Enzyme Function

VDR
• Vitamin D receptor is involved in mineral metabolism, immune
function and dopamine synthesis.

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 VDR (Vitamin D receptor) SNP

SNPs in VDR decrease the affinity of the D3

receptor

Associated with osteopenia/ osteoporosis,

immune function, cancer, fatigue, cognitive
decline & Alzheimer’s risk

• Beydoun MA, Ding EL, Beydoun HA, Tanaka T, Ferrucci L, Zonderman AB. Vitamin D receptor and megalin gene polymorphisms and their associations with longitudinal cognitive
change in US adults. Am J Clin Nutr. 2012 Jan;95(1):163-78. [PMID: 22170372]
• Jingwi EY, Abbas M, Ricks-Santi L, Winchester D, Beyene D, Day A, Naab TJ, Kassim OO, Dunston GM, Copeland RL Jr, Kanaan YM. Vitamin D receptor genetic polymorphisms
are associated with PSA level, Gleason score and prostate cancer risk in African-American men. Anticancer Res. 2015 Mar;35(3):1549-58. [PMID: 25750310]
• Du Y, Hu L, Kong F, Pan Y. Lack of association between vitamin D receptor gene BsmI polymorphism and breast cancer risk: an updated meta-analysis involving 23,020 subjects.
Tumour Biol. 2014 Mar;35(3):2087-93. [PMID: 24248540]
• Mauf S, Penna-Martinez M, Jentzsch T, et al. Immunomodulatory effects of 25-hydroxyvitamin D3 on monocytic cell differentiation and influence of vitamin D3 polymorphisms in
type 1 diabetes. J Steroid Biochem Mol Biol. 2015 Mar;147:17-23. [PMID: 25448747]
• Feng M, Li H, Chen SF, Li WF, Zhang FB. Polymorphisms in the vitamin D receptor gene and risk of autoimmune thyroid diseases: a meta-analysis. Endocrine. 2013
Apr;43(2):318-26. [PMID: 23065592]
The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Enzyme Function

COMT
• Catalyzes phase II detoxification (metabolism) of neurotransmitters
dopamine, epinephrine, and norepinephrine, as well as estrogen.

• Neurodegener Dis. Author manuscript, available in PMC 2014 October 13. Influence of single nucleotide polymorphism in COMT, MAO-A, and BDNF genes on
dyskinesias and Levodopa Use in Parkinson’s Disease. P. Cheshire. K.Bertram. H. Ling. SS. O’Sullivan. G. Halliday. C. McLean. J Brass. T. Foltynie. E. Storey and DR
Williams.
• J Clin Psychopharmacol. 2009 Aug;29(4):372-7. doi: 10.1097/JCP.0b013e3181ac4aaf. Monoamine oxidase a and catechol-o-methyltransferase functional
polymorphisms and the placebo response in major depressive disorder. Leuchter AF1, McCracken JT, Hunter AM, Cook IA, Alpert JE.
The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 COMT (Catechol-O-methyltransferase) SNP
SNP’s in COMT confer both upregulated and down
regulated enzyme activity and subsequent dopamine
levels

Low COMT activity (high levels of dopamine)

High COMT activity (low levels of dopamine)

• Am J Hum Genet. 2004 Nov;75(5):807-21. Epub 2004 Sep 27. Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and
enzyme activity in postmortem human brain. Chen J1, Lipska BK, Halim N, Ma QD, Matsumoto M, Melhem S, Kolachana BS, Hyde TM, Herman MM, Apud J, Egan MF, Kleinman JE,
Weinberger DR.
• Science. 2006 Dec 22;314(5807):1930-3. Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure. Nackley AG1,
Shabalina SA, Tchivileva IE, Satterfield K, Korchynskyi O, Makarov SS, Maixner W, Diatchenko L.
The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Biopterin Gear Core SNPs

• MAO-A
• MAO-B
• COMT
• VDR

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Biopterin Gear
Imbalances may lead to these clinical patterns:
Severe depression
or non-drug Cardiac
responsive dysfunction
depression

IBS Brain fog

• Arch Dis Child. 1986 Feb;61(2):130-7. Neurological aspects of biopterin metabolism. Smith I, Leeming RJ, Cavanagh NP, Hyland K. Antioxid Redox Signal. 2014 Jun
20;20(18):3040-77. doi: 10.1089/ars.2013.5566. Epub 2014 Mar 14. Tetrahydrobiopterin in cardiovascular health and disease. Bendall JK1, Douglas G, McNeill E, Channon KM,
Crabtree MJ.
• Psychiatr Danub. 2015 Mar;27(1):25-30. Urinary neopterine levels in patients with major depressive disorder: alterations after treatment with paroxetine and comparison with healthy
controls. Taymur I1, Özdel K, Özen NE, Güngör BB, Atmaca M.
The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Nutritional Cofactors of Biopterin Gear

• P5P (pyridoxine B6)

• Magnesium
• Vitamin C
• SAMe
• Phenylalanine, tryptophan, tyrosine
• Vitamin D
• MB12 / 5-MTHF
• B complex

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
Function of NOS (Nitric Oxide Synthase)

• Synthesis of nitric oxide

• Arginine & biopterin (BH4)
dependent

• Curr Opin Clin Nutr Metab Care. 2010 Jan;13(1):97-104. doi: 10.1097/MCO.0b013e328332f99d. Regulation of nitric oxide production in health and disease. Luiking YC1,
Engelen MP, Deutz NE.
• BMC Med Genet. 2014 Jan 16;15:9. doi: 10.1186/1471-2350-15-9 Endothelial nitric oxide synthase gene polymorphisms and risk of diabetic nephropathy: a systematic review
and meta-analysis. Dellamea BS1, Pinto LC, Leitão CB, Santos KG, Canani LH.

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Function of NOS

eNOS(NOS-3) (rs 1799983, rs 2070744)

The endothelial isoform and primary signal generator in the control of vascular
tone, insulin secretion, & airway tone. Constitutively active

iNOS (NOS-2) (rs 2297518)

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 NOS SNP

• May cause down regulation

NOS SNPs: and reduced enzymatic
activity

• Inefficient conversion of
arginine into nitric oxide
Slow NOS activity
results in:
• Production of toxic free
radicals superoxide and
peroxynitrite

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
professionals are responsible for their own independent treatment decisions relative to their patients. Not responsible or liable for any advice, course of treatment, or diagnosis made by a health care professional, nor for any course of action taken by an individual.
 Nitric Oxide Gear
Imbalances may lead to these clinical patterns:
Vascular Oxidative
Raynaud’s
insufficiency stress

Brain fog IBS / SIBO

• Curr Opin Clin Nutr Metab Care. 2010 Jan;13(1):97-104. doi: 10.1097/MCO.0b013e328332f99d. Regulation of nitric oxide production in health and disease. Luiking YC1, Engelen MP,
Deutz NE.
• BMC Med Genet. 2014 Jan 16;15:9. doi: 10.1186/1471-2350-15-9 Endothelial nitric oxide synthase gene polymorphisms and risk of diabetic nephropathy: a systematic review and
meta-analysis. Dellamea BS1, Pinto LC, Leitão CB, Santos KG, Canani LH.
• Rossi GP, Maiolino G, Zanchetta M, Sticchi D, Pedon L, Cesari M, Montemurro D, De Toni R, Zavattiero S, Pessina AC. The T(-786)C endothelial nitric oxide synthase genotype
predicts cardiovascular mortality in high-risk patients. J Am Coll Cardiol. 2006 Sep 19;48(6):1166-74. Epub 2006 Aug 28.[PMID: 16979000]
• Dhillon SS, Mastropaolo LA, Murchie R, Griffiths C, Thöni C, Elkadri A, Xu W, Mack A, Walters T, Guo C, Mack D, Huynh H, Baksh S, Silverberg MS, Brumell JH, Snapper SB, Muise
AM. Higher activity of the inducible nitric oxide synthase contributes to very early onset inflammatory bowel disease. Clin Transl Gastroenterol. 2014 Jan 16;5:e46. doi:
10.1038/ctg.2013.17. [PMID: 24430113]
The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
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 Nutritional Cofactors NOS Gear

• BH4
• B2
• B3
• Arginine
• Calmodulin

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
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 Clinical Patterns for Use of NO Strips for
Monitoring NOS and Ammonia
Upregulated Can produce H2S which can contribute to GERD, SIBO, IBS
Transsulfuration
Pathway

Molybdenum & Are beneficial for helping to decrease the amount of sulfur by
Manganese products in the body

Manganese Lowers Ammonia and preserves Biopterin

Supports pancreatic enzyme output, dopamine synthesis, &

helps with brain fog
NO Strips Can be used to monitor NO synthesis and balance

Serum Ammonia Can be measured while on Manganese to monitor effects

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
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 Summary

All patients have unique polymorphisms which alters the

functioning of the gears.

Understanding genetic markers and pathways can lead

to a new kind of medicine that is
Precise, Personalized & Preventative!

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 QUESTIONS?

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 Legal Disclaimer
The contents of this document are provided for informational
purposes only, to scientists, health care professionals, and
academics. Neither the statements in this document nor
statements made by the presenter should be interpreted as
providing medical advice, a physician-to-physician consultation,
professional diagnosis, a medical or health-related opinion,
treatment, or services to you or any other individual; nor should
they be interpreted as recommending any product, therapy, or
course of treatment. Health care professionals are responsible for
their own independent treatment decisions relative to their
patients. Not responsible or liable for any advice, course of
treatment, or diagnosis made by a health care professional, nor for
any course of action taken by an individual.
The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
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 Thank you!

The contents of this document are provided for informational purposes only, to scientists, health care professionals, and academics. Neither the statements in this document nor statements made by the presenter should be interpreted as providing medical advice, a
physician-to-physician consultation, professional diagnosis, a medical - or health-related opinion, treatment, or services to you or any other individual; nor should they be interpreted as recommending any product, therapy, or course of treatment. Health care
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