“An ideal regimen to fight against the single most important

metabolic disease which can affect nearly every organ system in

the body”

* Inhibition of Glucose absorption Helps to support the benefits

* Stimulates insulin secretion/action of controlling diabetes
* Prevents PUFA peroxidation beyond the Glucose
Metabolism &
* Improves capillary function
Cardiovascular function
* Improves insulin binding
* Improves insulin sensitivity

CONTENTS
1. Introduction * Methylhydroxy chalcone polymers 6. Insulike - A Nutri Phenotypic
2. Metabolic Syndrome - An Over view * 4-Hydroxy isoleucine Approach specific nutrients
3. Causes of Metabolic Syndrome * Anthocyanins in Insulike with the
4. Traditional approach for Type-II * Alphalipoic acid biochemical and genetic
Diabetes Insulin Therapy * Chromium effects to help protect from
5. Insulike - A Nutri Phenotypic * Vitamin C, D3, E, K & Biotin disease
Approach Ingredients * Benfotiamine 7. Lactonova awareness
* Eugenia Jambolana Extract * Amino acids - Isoleucine, information -Life support
* Curcuminoids Glycine, N-Acetyl cysteine, L- benefits of exercise & stress
* Berberine Hydrochloride Glutathione management
* Cynanins 8. Benefits of slow release
* Banaba Leaf Extract 9. Conclusion - Future direction
* Charantin 10. Prescribing info & References
A Product Review
 A Nutriphenotypic
Insulike
TM

Tablets
Approach
METABOLIC SYNDROME (METS)
An Overview
Although metabolic syndrome (commonly referred to as and sleep apnea.
MetS) is a somewhat elusive diagnosis, the health
ramifications can be of significant consequence. There
is no agreed upon definition of MetS, but the current
consensus between the International Diabetes
Foundation and the American Heart
Association/National Heart, Lung, and Blood Institute is
that MetS is defined as the presence of three or more of
the following:

 increased waist circumference (≥102 centimeters/40

inches in men and ≥88 centimeters/34 inches in
women)

 elevated blood pressure (≥130/85 mmHg)

 elevated blood sugar (fasting glucose ≥100 mg/dL)

 high triglycerides (≥150 mg/dL)

 low high-density lipoprotein (HDL) cholesterol (<40

mg/dL in men and <50 mg/dL in women)
In addition, patients with MetS frequently demonstrate
elevated low-density lipoprotein (LDL) and total
cholesterol, smaller LDL particle size, elevated
inflammatory markers (such as C-reactive protein [CRP]
and fibrinogen), endothelial dysfunction, and high
homocysteine.
It is estimated that 25 percent of the world's adult
population meet the criteria for a MetS diagnosis. In the
United States, the prevalence might be even higher, with
the National Health and Nutrition Survey (NHANES)
reporting that 34 percent of adults meet the MetS
criteria.1 The risk for MetS also increases with age and
body mass index (BMI) (Table 1).
Table 1. Association between BMI and MetS Risk for Men and Women
BMI / Gender Prevalence Risk Compared to
of MetS Normal Weight
BMI <25 (normal or 7% Base line
underweight males)
BMI 25-29.9 (Overweight males) 30% 6 times the risk
BMI=30 (obese males) 65% 32 times the risk
BMI<25 (normal or underweight 9% Base line
females)
BMI 25-29.9 (overweight females) 33% 5.5times the risk
BMI=30 (obese females) 56% 17 times the risk

MetS is associated with increased risks for a number of

comorbidities, including cardiovascular disease, Type 2
diabetes, fatty liver, polycystic ovary syndrome (PCOS),
 Cardiovascular Disease / Diabetes represents a syndrome with disordered metabolism of
Individuals with MetS are three times more likely than carbohydrate and The most prominent clinical
those without MetS to have a stroke or a heart attack, and fat.
feature is hyperglycemia (fasting plasma glucose level
twice as likely to die from these events. The risk of >126mg/ dL, or glycosylated hemoglobin Alc (Hb Alc)
developing type II diabetes is five times higher in > 6.9%) .5 in most patients with Type 2 diabetes the
patients
onset is in adulthood most commonly in obese people
with
MetS2. over 40Hypertension,
years of age. hyperlipidemia and atherosclerosis
INTRODUCTION are often associated with
diabetes.
Diabetes mellitus is chronic metabolic disorder that 3. [Link] Med. Assoi. 2002 Mar ; 100(3): 144-8.
4. Diabetes 1996 Vital Statastics. Alexandria, VA: American Diabetes
has a significant impact on the health, quality of life Association.
and life expectancy of patients, as well as on the 5. No Authors listed. Report of the Expert Committee on the Diagnosis and
Classification of Diabetes Melllitus. Diabetes Care 1997;20:1183-1191.
health care system. In India it is estimated that
presently 19.4 million individuals are affected by this
deadly disease, which is likely to go up by 57.2 Non-alcoholic Fatty Liver Disease (NAFLD)
3
million by the year 2025. Diabetes is divided into two
major categories: Type 1 diabetes (formerly known as NAFLD is closely associated with metabolic syndrome
insulin dependent diabetes mellitus or IDDM) and (its incidence increases as weight increases). NAFLD is
Type 2 diabetes (formerly known as non - insulin the primary cause of elevated liver enzymes. Liver
enzymes should be tested in all patients with suspected
dependent diabetes mellitus or NIDDM) the overall
MetS, and MetS with a fatty liver comorbidity should be
prevalance of diabetes is approximately 60% of the Type 2 diabetes
ruled out in patients with elevated liver enzymes. Weight
population of which 90% is Type 2.4 loss and addressing other aspects of MetS are central to
treatment of fatty
Sleep Apnea liver. Causes Metabolic Syndrome?
What
Obesity is at the heart of the worldwide increase in the
prevalence of sleep apnea, a condition commonly Proposed unbalanced mechanisms
associated with MetS. In addition to the epidemiological 1. Nutrient Deficiencies
association between the two, it appears that imbalances Although it is easy to consider metabolic syndrome as
brought on by sleep apnea contribute to some of the attributable to excesses, there are several nutrient
symptoms seen in MetS. For instance, studies indicate deficiencies associated with this condition. The most
sleep apnea increases cortisol levels, which are in turn extensively researched deficiencies are magnesium,
6
associated with obesity and insulin As many vitamin D, and chromium.
resistance.
as 70 percent of obese Type 2 diabetics experience sleep MAGNESIUM
6
apnea . Magnesium is one of the most clearly identified nutrient
Polycystic Ovary Syndrome (PCOS) deficiencies in patients with MetS. Prior to identifying it
Many aspects of metabolic syndrome are also observed as “metabolic syndrome,” researchers were examining
in women who have PCOS – including insulin the combination of insulin resistance, hyperinsulinemia,
resistance, obesity in some cases, and dyslipidemia. essential hypertension, ischemic heart disease, and
Statistics indicate approximately
30 percent of women with PCOS magnesium deficiency (Reaven-Modan
have impaired glucose tolerance, while an additional 7.5 syndrome)9.
Studies clearly show that insulin sensitivity declines in
percent have . All women with a diagnosis of
diabetes7
PCOS or symptoms suggesting a diagnosis of PCOS healthy subjects when a state of magnesium deficiency is
(infertility, hirsutism, and oligomenorrhea) should be induced10. A large, prospective, 15-year study of
tested for hyperglycemia and dyslipidemia. young American adults found a 31-percent increase in
MetS in the group of subjects with the lowest
How to Determine Body Mass Index magnesium intake11.
Multiply weight in pounds by 703 Square the height in A study on hair mineral content foundlower magnesium-
inches Divide the first number (weight x 703) by the 12
to-calcium ratios in individuals with insulin resistance .
Lower intakes and lower blood levels of magnesium are
second number (height associated with an elevation in inflammatory markers,
squared) while higher magnesium intakes and higher blood levels
9
demonstrate a protective
Alternate metric method:effect .
Divide weight in kilograms by height in meters squared As discussed above,
(kg/m2) these inflammatory markers are associated with MetS.
The Inflammation Connection
Obesity is known to be associated with low-level VITAMIN D
inflammation. The inflammation occurs first in the Vitamin D plays a role in MetS. Studies show vitamin D
adipocytes, with an increase in tumor necrosis factor- has a role in immune system function, inflammation,
alpha (TNF-α)8. TNF-α stimulates a more parathyroid levels, pancreatic beta-cell function, and
general inflammatory state that can ultimately result in mineral balances that are key to the pathogenesis of the
insulin resistance and endothelial dysfunction, which disorder13.A meta-analysis of 28 studies showed
can contribute to hypertension and other vascular that, when compared to higher vitamin D levels, lower
complications (Figure 1). serum levels of 25-hydroxyvitamin D were associated
with a 55- percent increase in diabetes, a 33-percent
increase in the risk of cardiovascular diseases, and a 51-
14
percent increase in metabolic syndrome .

CHROMIUM
Figure 1. Association between Obesity, Inflammation, and Metabolic Syndrome
Chromium is not found in sufficient amounts in food to
Obesity
AdipocytesLocal Inflammation in Adipocytes (fat cells) replenish tissue stores or to affect clinically significant
caused by TNF-
improvement in blood glucose control. Current
estimates indicate 80 percent of Americans are deficient
Generalized Insulin Resistance; in this essential mineral nutrient, andhigh in simple sugars
diets
Inflammation IL-6; Endothelial Dysfunction 15
Adiponectin* can deplete chromium from the body . In a study of 123
males (63 with MetS; 60 controls), those with MetS had
lower hair chromium concentrations than healthy
controls12.
2. Dietary Excesses sweetened beverages show HFCS-containing beverages
increase MetS symptoms at a higher rate than other sugar-
SUGAR-SWEETENED SODAS containing beverages18,19. Other research has outlined
When examining the effects of sugar-sweetened beverages the potential health outcomes associated with HFCS (Table
on MetS parameters, researchers found plasma 2)20.
triglycerides and waist circumference, both aspects of
MetS, increased as the number of sugared beverages Forty-eight percent of Indians drink an average of one
16
increased . soda daily, putting them at greater risk for MetS or type 2
diabetes.
DIET SODAS
Table 2. High-Fructose Corn Syrup Potential Contributions to MetS

Weight gain / obesity Leptin resistance

Insulin resistance Increased protein
High-Fructose Corn Syrup Lipid production glycosylation
by the liver Type 2 diabetes
Increased triglycerides
As awareness of the negative effects of sugar-sweetened
sodas has increased, many people who choose diet sodas
have the misconception that these beverages provide a
healthier choice. Unfortunately, data indicates the
opposite toIndividuals
be true. with an “at least daily” intake of diet
soda were shown to have a 36-percent greater risk of
developing metabolic syndrome and a 67-percent greater
risk of developing type 2 diabetes compared to individuals
who consumed no diet
17
beverages .
HIGH-FRUCTOSE CORN SYRUP(HFCS)

Studies comparing HFCS-sweetened beverages to sugar-

3. Other Dietary Excesses abnormalities.
Researchers are concerned that the effects of these
In evaluating questionnaires from different subjects chemicals will be amplified because chemical
that compared dietary factors and MetS incidence production now exceeds 400 million tons globally24.
for nine years, researchers found BPA has been shown to have “consumption of a Western
significant adverse effects
dietary pattern” that is high in meat, fried foods, and diet
soda promoted the development of metabolic
Lack of Exercise syndrome
21
.
on estrogen signaling, even at small doses25. This
Lack of physical activity has long been associated signaling can alter glucose transporter function, cause
with adverse impacts on metabolic health, including hyperglycemia, interfere with hypothalamic regulation
an increase in abdominal fat and a decrease in
of weight, result in adiposity, and impair energy
insulin sensitivity. As a person becomes less active,
BMI, waist- hip ratio, waist circumference, and expenditure26.
obesity go up22. Even in adolescents, lack of
exercise and low cardio-respiratory fitness are Most chronic health problems, including stubborn
associated with increased risk for MetS23 . weight gain, unrelenting fatigue, high blood
pressure, creeping cholesterol, and high blood
Potential Contributions to MetS
Environmental Toxin Exposure sugar, are not found in simply one organ, but in
Increasing evidence over the past decade indicates several parts of the body. This is the result of years
that chemicals in the environment can contribute to of slow, subtle challenges to one's unique
the hormonal imbalances that result in metabolic metabolism.
disruption in society at large. Human
epidemiological data and numerous animal studies Lifestyle habits, stress levels, prescription drug
specifically associate endocrine- disrupting use, relationships, inherited genes, and the
chemicals, such as organochlorine pesticides (like environment can all dictate one's current state of
DDT), dioxins (like PCBs), and flame retardants health. Cracking the Metabolic Code helps
(PBDEs), with metabolic syndrome. Studies also both practitioner and patient understand how
link these factors can affect health and what can be
exposure to the plasticizing agents bisphenol-A(BPA) done to reverse them.
and phthalates to insulin resistance, obesity, and liver
4. Stress In cases of suspected MetS, serum liver enzymes should
Stress is a well-known contributing factor to obesity. In be tested. Laboratories offer additional markers to
a study of 10,308 men and women ages 35-55, determine the state of long-term blood sugar levels
workplace stress measured over a 14-year period was (HbA1c), inflammation (e.g., high sensitivity C-reactive
positively associated with an increased risk for protein, TNF-α), insulin secretion (e.g., insulin,
metabolic syndrome. Employees with chronic work proinsulin, and C-peptide), thrombosis (e.g.,
stress were twice as likely to develop MetS than plasminogen activator-1 [PAI-1] and fibrinogen), and fat
27
individuals without work stress . metabolism associated hormones (e.g., adiponectin and
leptin).
How can stress cause metabolic syndrome? Hormones produced in fat cells – adiponectin and
Figure 2 illustrates some of the factors involved. For a leptin
more detailed discussion on the relationship between are shown to have an increasing role in regulating
hormones, neurotransmitters, and metabolism, the book
inflammation, insulin sensitivity, appetite, and energy
Cracking the Metabolic Code is highly recommended.
metabolism.28, 29

Figure 2. The Connection Between Chronic Stress and Obesity TRADITIONAL APPROACH FOR
TYPE-II DIABETES
Chronic Stress
INSULIN THERAPHY
Insulin is usually added to an oral agent when glycemic
Cortisol
^ control is suboptimal at maximal doses of oral
Fat
Obesity
^Blood Sugar + ^Food Cravings
(via gluconeogenesis production
Prod
uctio

of glucose from protein)

^ n
(Lip
Insulin ogen
esis)
^ (Hyperinsulinemia)
medications. various curre therapies.)
(Table 1 limitatio nt
summarizes ns of drug Table 1. Limitations of Hypoglycemic Medications

Anti - Diabetic Drugs Mechanisim of action Limitations/Side effects

Laboratory Evaluation Sulfonylureas

Dry (Torbutaline & glyburide)
Enhance insulin secretion from the
Pancreatic beta cells
Hypoglycemia, weight gain

Biguanides Gastrointestinal disturbances

The basic markers for diagnosis and follow-up of MetS

Reduces plasma glucose via inhibition of
Dry (Medformin) hepatic glucose production & increase
muscle glucose uptake

patients include the measuring of waist circumference,

Alpha-glucosidase inhibitors Gastrointestinal disturbances
Decreases post prandial levels by
Dry (acarbose)
interfering with carbohydrately gerhins &
delayrs gastro internal absorphon

blood pressure, blood sugar, triglycerides, and Thiazolidinediones

Dry (troghtazone, rosightazone & Improving insulin sensitivity in the muscle
Liver toxicity, weight gain, high LDL
cholestrerol, high cost
pioghtazone) to a much lesser extent in the liver

cholesterol fractions (see page 1 for abnormal levels of Meglitinides Hypoglycemia, weight gain

these diagnostic markers for MetS). The goal is to Dry (Repahinide) Augment insulin secretion

Insulin Hypoglycemia, weight gain

achieve the following: —

 women: waist circumference <34 inches; men:

PHARMACOLOGICAL
waist circumference <40 inches TREATMENT & LIMITATIONS
 blood pressure ≤120/80 mmHg
 fasting blood sugar <100 mg/dL By conventional standards, oral therapy is indicated in
 triglycerides <150 mg/dL any patient with Type 2 diabetes in whom diet &
 HDL-cholesterol levels >50 mg/dL in women exercise
fail
30
to achieve acceptable glycemic control . Although
and initial responses may be good oral hypoglycemic drugs
>40 mg/dLin men may lose their effectiveness in a significant percentage
of patients. The drug categories include sulfonylureas,
biguanides, aplha-glucosidase inhibitors,
thiazolidinediones, and meglitinides.

30. American Diabetes Association. Clinical practice recommendations

1995. Position statement: diabetes mellitus and [Link] Care
1995; 18:28.

EUGENIAJAMBOLANAEXTRACT

Eugenia Jambolana is a fruit; it is a flavonoid rich extract. It is

long known for its Anti diabetic activity in traditional
INSULIKE contains all essential natural botanicals and medicines. Studies have proved that the various biological
nutrients to address factors associated with MetS* and
specifically diabetes.
Serving size : 1 Tablet
INSULIKE contains vitamins and minerals often found
to be deficient in MetS, diabetic patients for example, Each film coated tablet contains
each serving contains 400 IU (10mcg) of vitamin D3, 40 Eugenia Jambolana extract 100mg
mg of vitamin C and 40 mcg chromium* and 55mcg of Curcuminoids 50mg Epigallocatechin gallate (EGCG) 10mg
Berberine Hydrochloride 50mg from Greeen tea extract
selenium. Mulberry leaf extract 4:1 33.5mg Alpha lipoic acid 100mg
Cynarins 5mg Chromium (as Chromium picolinate) 40mcg
from Artichoke leaf extract Selenium (as L-Selenomethionine) 55mcg
Banaba leaf extract 12mg Magnesium 40mg
L-Glutathione 2.5mg Vitamin C 40mg
Gymnemic acids 10mg Vitamin D3 10mcg
from Gymnema sylvestre extract Methylcobalamine 500mcg
Charantin 10mg Vitamin E 12mg
from Bitter melon exract Vitamin K 30mcg
Methyl hydroxy chalcone polymers 6.25mg Vanadium 1mg
from Cinnamon extract Biotin 50mcg
isoleucine 1.25mg Benfotiamine 25mg
from Fenugreek Isoleucine 25mg
Anthocyanins 3.10mg Glycine 25mg
 from Bilberry fruit extract N-acetyl cysteine 25mg

Help maintain healthy blood sugar levels*

Support normal lipid levels*

Increases satiety*

Support insulin sensitivity*

Provide nutrient support for fatty liver*

parameters such as glucose tolerance, lipid profile, Figure: 04 Effect of Eugenia Jambolana
glycogen Extract Postprandial Blood Sugar in 10 Healthy
Volunteers Control

biosynthesis, glucose uptake and insulin release. It has a Eugenia Jambolana Extract 1.5g

Blood Glucose (mg /dL)

Eugenia Jambolana Extract 3.0g

dual hypoglycemic and hypolipidemic effect. 120

Bhavna Sharma, [Link], Rajani salunke, parta Roy

100
DOI: 10.1016/[Link] chem..2008.02.068.

INSULIKE contains the seed extract of Eugenia 75

Jambolana Extract this botanical was heavily researched
in Europe as an anti-diabetic agent prior to insulin
development.
Unpublished research on the specific extract Eugenia
Jambolana Extract found a 20-percent decrease in blood
sugar levels after a carbohydrate load (50 grams of white
rice) in healthy volunteers (Figure 4). Another
unpublished study conducted on 40 patients with Type 2
diabetes found
Eugenia Jambolana Extract (average 2-3 grams daily)
 Figure: 05 Effect of Eugenia Jambolana Extract on
an Average Fasting Blood Sugar Level Over Time
200
190
180
170
160

Glycemia (mg/dL)
150
0 25 50 75 100 125 150
140
Min.

197± 11

resulted in a 35-percent reduction in fasting blood sugar 130

120
128± 10 127± 8*

after 15 days and a 49-percent reduction after 90 days 110

100
103± 7* 101± 5*

Figure 4. 90
0 15 30 Days
60 90

Nalx, Liy, Pan HZ, ZhouXL, Sun DL, Meng M 2013 sep; 57((): 1569-77
In a small, unpublished pilot study, 13 Type 2 diabetics
(nine were not on oral hypoglycemic medications) were
given varying dosages of Eugenia Jambolana Extract
(from 1.5-6 g daily) for 10 weeks. Fasting blood sugar
dropped an average of 33 percent (n=12), while
postprandial blood sugar dropped an average of 35
percent (n=10) (Figure 6).*

Eugenia Jambolana Extract was evaluated at a hospital at

doses of 1-6 g (average 1.5 to 3 g) for periods from two
weeks to six months. Significant decreases in fasting
blood sugar were reported in several evaluations of Type 2
diabetics (ranging from 13 to 112 subjects).*In two smaller
observational studies, Eugenia Jambolana Extract was
found to improve the effect of oral hypoglycemic
medications in Type 2 diabetics who were not well
controlled with the medications *
alone.
The mechanisms of action of Eugenia jambalona extract
include activation of glucose transport, improved
28
glycogen storage, and stimulation of insulin release.
Laboratory studies support Eugenia jambalona extract
31,32
bility to improve blood glucose and lipid profiles.

CURCUMINOIDS:
Curcuminoids exerts glucose lowering effect and
improvise
insulin resistance in Type II Diabetes. This action of
Curcuminoids is due to reducing serum free fatty acids
(FFAs) andTheincreasing
study hasfatty acidthat
proved oxidation in skeleton
curcuminoids are
muscle.
effective in lowering glucose in blood in type II diabetes.
 inflammation.
Curcumin has been shown to ameliorate
33,34
many of the inflammatory and metabolic
dearrangements
associated with metabolic
A highly absorbable curcumin to help maintain Supplementing
syndrome. with curcumin can benefit patients
with pre-diabetes:
healthy inflammatory-mediator levels.* In a double-blind, placebo-controlled trial, 240 pre-
Curcumin : Effects on Aspects of diabetic patients were given 750 mg curcumin or
Metabolic Syndrome placebo twice daily for nine months. After nine months,
16.4% of patients in the placebo group, compared to no
 Fasting blood sugar*
53
 Adipogenesis*
56
patients in the curcuim group, had progressed to Type 2
diabetes.
Beta-cell function*
53 Leptin
 fibrosis Liver 57
in fatty liver* Chuengsamarn S, Rattanamongkolgul S,
Luechapudiporn R,et [Link] Care 2012;35:2121-2127.

 Inflammation58in
53
Adiponectin levels*
adipocytes* Steigerwalt R, Nebbioso M, Appendino G, et al.
Panminerva Med 2012;54(Suppl 4):11-16
53, 59
 Triglycerides*54 Insulin sensitivity*
Curcumin can benefit patients who have high
Circulation*
55
triglyceride levels:
In a randomized, double-blind trial, 1g/day of Curcumin
The inflammation can occur first in obesity is known to be associated with low levels of
6
the adipocytes, with an increase in TNF-α. TNF-α or placebo was given to obese, non-diabetic patients
stimulates a more general inflammatory state that can (n=30) for 30 days. Curcumin was shown to significantly
ultimately result in insulin resistance and endothelial promote normal level of triglycerides.
dysfunction, which can contribute to hypertension Mohammadi A, Sahebkar A, Iranshahi M, et al.
and other vascular complications. Phytother Res 2013;27:374-379.

Curcumin might have benefits in other obesity-

related conditions: Change from Fasting Blood Glucose
Several animal and Invitro studies have demonstrated Concentration (mg/dl)
benefits for insulin resistance, adipocyte inflammation, Influenc of mulberry leaf extract on the blood glucose and breath
weight management, fat loss, liver fibrosis, and hydrogen response to ingestion of 75g sucrose by subjects with
Type 2 diabetes and controls.
inflammatory response.

BERBERINE HYDROCHLORIDE 120

A
Berberine is an isoquinoline derivative alkaloid with
hypoglycemic effect was first Reported in 1998.
Berberine showed improved blood glucose control
compared with conventional anti diabetic therapy
In a study of patients with Type 2 diabetes for at least
In addition effect was enhanced when combined with
hypoglycemic five years, 3790patients received 500 mg curcumin Twice
anti diabetic agent. It also has Positive effect on plasma daily plus standard care, while 38 patients received
standard care60only (control). After four weeks, Visual
activity, peripheral
30 blood flow, and retinal and peripheral
edema showed statistically significant improvement in
0
the curcumin group compared to the controls.
-30

-60
0 30 60 90 120 150 180 210 240
lipid profile in diabetic patients. It also has additional
cholesterol lowering effect in treating diabetes Recent
studies have shown this impressive alkaloid has beneficial
actions on metabolic activities. As a potent regulator of
90
intracellular metabolism, Berberine affects cellular 120
B
uptake of glucose, beta-oxidation of fatty acid, insulin 60

sensitivity, and glucose transportation. 30

Hui Dong,Nanwang, Lizhao; and Fuerlu; No serious adverse sideffects except for 0
mild to moderate G.I. disturbances.

MULBERRY LEAF EXTRACT Mulberry

-30 leaf extract contains compounds such as
-60
0
 35
Fagomines which induces insulin secretion ,antioxidants
that putatively reduce lipid peroxidation36, considered
37
safe as food supplement in Asia .
30 60 90 120 150 180 210 240
Beneficial effects upon ingestion of Mulberry extract
Time (minutes)
 Inhibits intestinal Sucrase .
 Induce sucrose malabsorption. Changes in blood glucose concentration from the fasting
concentration of 10 healthy controls (upper panel (A) ) and 10
 Reduce microvascular complications of diabetes38. subjects With Type 2 diabetes (lower panel (B)) after ingestion of
75 g sucrose with 1.0 g of Mulberry leaf extract(white squares) or
35. Taniguchi S, Asano N, Tomino F, Miwa I. Potentiation of glucose induced placebo ( Black circles ). The significance of difference between
insulin secretion by fagomine, a pseudo sugar isolated from mulberry leaves. mulberry leaf extract and placebo over the first 120 minutes of the
Horm. Metab. Res. 1998 ;30:679-683 study, determined by ANOVA, was highly significant for
controls(P=0.0050 and subjects with diabetes(p=0.002).
36. J. Nutr 2005; 135: 729-734
Clin. Chem Acta 2004; 348: 215-218
Clin Chem Acta 2001; 314: 47-53

37. Int. J. of Food sci. And Nutr, taylao and Francis ltd, 2003;54:411-416.

38. Diabetes care in press, published online Feb 15 2007.

CYNARINS FROM ARTHICHOKE LEAF GYMNEMIC ACIDS FROM GYMNEMA

EXTRACT: SYLVESTRE EXTRACTS
Arthichoke is a plant. The leaf, stem, and roots are used
to make 'Extract' which contains a higher concentration Gymnema Sylvestre(Sugar Killer) is a medicinal Plant
of certain chemicals found in the plant. These extracts that grows in the open forest of India, China, Indonesia,
are used as medicine Cynara Scolymusl (Artichoke) acts Japan, Malaysia, Srilanka and South Africa.
as lowering glycemic effect. Clinical studies have The leaves of these plants are used as Antiallergic,
proven that Cynara Scolymus is capable of lowering Hypoglycemic, and Hypolipidimic. ([Link].2010)
post-pradial glycemia. It has been shown to help The studies have showed that the Gymnemic Sylvestra
maintain healthy glucose and cholesterol levels in Itobese
also extract, significantly decreases the plasma glucose
individuals.
level, it controlled gluconeogenic levels in Liver,
provides support for healthy bile flow and liver kidney and muscles ([Link].1990).
function.
Noemi Fantini, Gaencarlo Colombo, Andrea Giori DOI: 10.1002/PTP.3285, 24 Aug 2010.
It has a direct effect of increase in insulin level up to
50% (Bolkent [Link].2000, chattopadhay (1998).
COROSOLIC ACID from BANABA LEAF This extract showed significant decrease in triglyceride,
EXTRACT cholesterol and LDL cholesterol and increase in the
Corosolic acid impacts glucose parameters of Type 2 level of HDL Cholesterol, due to increase in Insulin
diabetes by way of insulin like activity, stimulating which resulted in increased activity of Lipoproteins
glucose uptake by body cells and inhibiting adipocyte Lipase.(Daisy [Link].2009) Studies showed that
differentiation. The corosolic acid in banaba leaf extract [Link] leaves treats complications like
has been shown to stimulate glucose transport activity Hyperglycemia, Hyper insulinemia, Hyperlipidemia
and significantly aids in regulation of blood sugar and Oxidative stress.
helps to lower
levels39. It serum insulin, urinary excreted glucose
and Ref : Aziza A.M. EL shafey, Magda
total plasma ,41,42 It is said to have a memory
[Link]. DOI : 10.1016/JJ
cholesterol40 . KSUS.2012.11.001

effect 43ofconfirmed safe and

blood glucose effective
lowering by the
even clinical
after intake is CHARATIN FROM BITTER MELON EXTRACT:
studies . Momordica Charantia is a fruit used for the Treatment of
diabetes and related conditions. It has a signicant anti
diabetic, and
39. Liu.F, im J, Lin X, Chen X, [Link] 2001, sep; 131(9):2242-7
cysteine,
40. Suzuki Y, Unno T, Leshitani M, Hayashi K, Kakuda T. J. Nutr. Sci.
Vitaminology(Tokyo)1999Dec; 45(6);791-795.
41. Hayashi T, et al Planta med 2002; Feb68(2), 173-5
stress.
42. Kakunda T, SakaneL, Takihara T, Ozaki Y, Takeuchi H, Kuroyanagi Glutathione exerts Glycemic control which
M, Biosci. Biotechnology Biochem 1996 Feb; 60(2)204-8. diminishes the incidence of diabetic microvasular
43. Murakami L, Myozak, Kasai R, Ohtani K, KurokawaT, Ighibasis,
complications by decreasing oxidative stress.
Dayrit F,Padolina WG, Yamasaki K. chem., Pharm bull (Tokyo)
1993, DEC; 41(12): 2129-31.43) Hattori K, et al activation of
lagerstroemeia Speciosa has insulin like activity. J. Pharmacol Sci.
93,1:69-73-2003

L- GLUTATHIONE:
Glutathione is a tripeptide Synthase from glutamate
lower cellular levelshyperglycemia
sustained of the antioxidants glutathione,
is associated with
which leadsds to tissue damage attributed to oxidative
Hypolipodemic activity so that it can be used as adjuvant skeletal muscle glucose utilization. (Cummings E Hundal, MS,
therapy along with allopathic medicine Studies has Wackerhage H, etal), inhibition of intestinal glucose uptake
reported that 'Charatin' a typical 'curditane type (VebansoT, Arai H, Taketaniy etal 2007), Inhibition of adipocyte
triterpenoid in M. Chantin is more effective than other differentiation (NerukarPV, Lee YK Nerukar Med 2010; 10.34),
hypoglycemic agents tolbutamine. Suppression of key gluconeogenic enzymes, preservation of islet
(Cousens G. North Atlantic book, 2008.) Beta cells and their functions (Gadang V, Gilbertw, Hettiara,
rehylhy N, Horax R, Katwal, Devareddy).
It shows hypoglycemic effect by stimulation of peripheral and

Rajagopal Vsekar MD, V Mckay, MD and Farool Jahoor Phd

Diabetic Care, Jan2011; 34(1): 162- 167

METHYL HYDROXY CHALCONE uptake in cell studies, other cinnamon polyphenols such as
POLYMERS FROM CINNAMON EXTRACT MHCPhave been shown to be potent insulin mimetic.
Aqeous extracts of cinnamon have been shown to MHCP / Type A Polymers mimics insulin, activates its
increase invitro glucose up take, glycogen receptors and
100
works synergistically with insulin in the cells.
synthesis, phosphorylation of insulin receptors and
44,45
aids in trigerring the insulin cascade system . A 80

INCREASE IN FLOURESCENCE
novel MHCP was identified , which increases the
60
glucose metabolism of the cells 20 fold in vitro in the
epididymal fat cell assay. The MHCP in cinnamon 40
strongly inhibits the formation of reactive oxygen
species in collagen-activated platelets in v i t r o ( f i g : 20

2 ) s o m a y p r o v i d e s y n e r g i s t i c 0
46
benefits .Cinnamon also contains procynadin
dimmers and oligomers of the type thought to improve
47
capillary function .

MHCP AND INSULIN HAVE SYNERGISTIC

EFFECT

We have isolated and charecterised the active

constituents from cinnamon and shown that they are
type A polymers ( A type doubly linked procynadin
polymers of the catechins and/or epicatechins, with a
molecular weight of 864 and 1152 respectively (few
studies show type A polymers as MHCP).These
complexes not only improve insulin function but also
work as antioxidants in Ferric reducing antioxidant
power (FRAP) assay and in prevention of copper
induced LDL [Link] A polymers potentiates
insuin activity and also inhibits insulin receptor
phophatase activity, thus mimics the action of insulin
induced signalling via its receptor48.
44. Impart rodosevich J, Deas S. Polansky, MM Beedke DA, IngerbrustenTS AndersonRA,
graves Dj; regulation of phosphorylase phophatase (PTP-1) and insulin receptor
kinase by fractions from cinnamon ; implications from Cinnamon regulation of insulin
signaling. Horm res 50; 177-182, 1998.
45. Jarvill-Taylor KJ, andrson RA, Graves Dj, A ydroxychalcon derived from cinnamon
functions as a mimetic for insulin in 3T3-L1 adipocytes. J AM. Coll. Nutr 20 ; 327-336,
2001. Coll. Nutr 20 ; 327-336, 2001.
46. Broadhust CL, Schmidt WS, Anderson RA, et al. Lipids, chromium and phytochemicals:
a synergistic approach to NIDDM. Essential fatty acids and eicosanoids; Invited
papers from the fourth conference july 1997. Prostaglandins leukot Essent Fatty acids
1997: 57:2002
47. Chem Pharm Bull1986; 34: 633-642.
48. Journal of American college of Nutrition, Vol. 20, No.4, 327-336(2001)

The polyphenol type A polymers from cinnamon up

regulates expression of genes involved in activation &
phosphorylation of insulin receptor and increase glucose
 0 2 4 6 8 10 12
Time

Figure 2. Inhibition of production of reactive oxygen

Cinnamon extracts have been shown to positively affect
species in platelets by metlylhydroxy chalcone numerous aspects of MetS in individuals with obesity,
polymer (MHCP) 49
pre-diabetes, diabetes, or PCOS (Table 3). In one study
using specifically the Cinamon extract, supplementation
of 6.25 mg twice daily or placebo for two months to 137
- No Extract added
- 5uL 2A

individuals with Type 2 diabetes significantly improved

- 5uL 1

fasting and postprandial glucose levels in the cinnamon

50
group. Each serving of INSULIKE contains 6.25 mg of
Cinamon extract.

MHCP in cinnamon extract shows positive affects of

several aspects of metabolic syndrome in individuals
with obesity , including maintenance of healthy blood
sugar , lipids, and lean muscle mass.

Whole blood is incubated with 10 M w2’7’- dichlorodihydrofluorescein diacetate for 10 min,

followed by a 5 min exposure to MHCP solution or vehicle control. Collagen at 20 ug/ml is
added, and platelets in the samples are monitored for increases in fluorescence by flow
cytometry at time indicated. Platelets are known to produce hydrogen peroxide,particularly
when collagen is used to stimulate them. MHCP 1 is mg/ml, and is likely to be a slightly lower
molecular weight than MHCP 2A (4.5 mg/ml). The data show a significant, dose-dependent
decrease in fluorescence with MHCP treatment

MHCP in Insulike
Increases insulin sensitivity by activating the
enzymes that stimulate insulin receptors, while
inhibiting the enzymes that deactivate them,
thus improves the way insulin works.
4 HYDROXY ISOLEUCINE FROM exerts hypoglycemic effects by stimulating glucose
FENUGREEK EXTRACT 54
dependant insulin secretion from pancreatic beta cells ,
as well as by inhibiting the activities of alpha amylase
The fraction of fenugreek that contains the testa (ie.. the 55
portion and the endosperm of the defatted seeds (ie.. The and sucrase , two intestinal enzymes in carbohydrate
subfraction are thought to be associated with the metabolism.
hypoglycemic effects of fenugreek, these effects have
not been observed in the studies of lipid extracts51 TABLE
and the extract used in INSULIKE is water extract. Safety : Areview of literature o fenugreek
It is possible fenugreek lowers lipids because it contains reveals .
50% fiber(30% soluble fiber and 20% insoluble fiber)
that can slow the post prandial glucose absorption. This
may be a secondary mechanism for its hypoglycemic
effect.

The hypoglycemic effects of fenugreek have been

attributed to several mechanisms, (savior et al) in vitro
studies demonstrated that the amino acid 4 hydroxy
isoleucine in fenugreek extract increased glucose
induced insulin release in human and rat pancreatic
52
islets .
The amino acid appeared to act only on pancreatic beta
cells, since the levels of somatostatin and glucagons
were
53
not altered . In human studies, fenugreek reduced the
area
under the plasma, glucose curve and increased the
number of insulin receptors, although the mechanism of
this effects is unclear, In humans, fenugreek extract
 seeds on intravenous glucose disposition in non insulin dependant diabetic
Fenugreek seed extract also lowers serum triglycerides, Patients. Phytother. Res 1994; 8: 83-86
56-60
Total Cholesterol (TC), and LDL . These effects may 54. Ajabnoor MA, Tilmisany Ak. Effect of trigonella foeum graceum on blood
glucose levels in normal and alloxin diabetic mice J. Ethno pharmacol 1988;
be due to sapogenins, which increase biliary cholesterol 22 : 45-49.
55. Amin R, Abdul Ghani As, Shleiman MS. Effect of trigonella foeum
excretion, in turn leading to lower serum gracecum on intestinal absorption. Proc. Of the 47 th annual meeting of the
60,61- American diabetes association9Indiana polis USA) Diabetes 1987; 36:2119.
cholesterols 56. Stark, Madar Z, The effect of an ethanol extract derived fenugreek on bile
63 acid absorption and cholesterol levels. Br. J. Nutr. 1993;69:277-287.
. The lipid lowering effect might also be attributed to 57. Petit P, sauvaire Y, Ponsin G, et al effects of fenugreek seed extract on
feeding behaviour. Metabolic-endocrine correlates. Pharmacol Biochem
its estrogenic constituent, indirectly increasing the Behav 1993; 45; 369-374.
58. Al. Habori, Al Agubari Am, Al-Mamery M. Effects of fenugreek seeds
thyroid and its extracts on plasma lipid profile. Phytother Res 1998;12 : 572-575.
64 59. Al- Habori M, Raman A. Antidiabetic andhypocholesterolaemic effects
hormone T4 . of fenugreek. Phytother Res 1998;12:237-242.
In animal and several human trials, fenugreek seed have 60. Valette G, Sauvaire Y, Baccao JC, Ribes G; Hypocholesterolaemic effect of
fenugreek seeds. Atherosclerosis 1984;50;105-111.
been found to lower the fasting serum glucose levels, 61. Sauvaire Y, Ribes G, Baccao JCet al . Implication of steroid saponins and
sapogenins in the hypocholesterolaemic effect of fenugreek. Lipids 1991; 26;
both acutely and chronically. The summary of the 191-197.
62. Varshney Ip, sharma SC, saponins and sapogenins ; Part xxxii. Studies on
studies have been shown in table. trigonella foenum graceum linn. Seeds. J. Indian Chem Soc 1966;43:564-567.
63. Sidhu GS, Oakenfull Dg, A mechanism for the
hypocholesterolaemic activity of saponins. Br.J. Nutr. 1986;55:643-
649
52. Savaire Y, Petit P, Broca C, et al 4-hydroxy isoleucine ; a novel amino acid,
64. Mishkinsy J Joseph , Sulman Fg, Hypoglycemic effect of trionella : Lancet
potentiator of insulin secretion. Diabetes 1998; 47:206-210.
1967; 2:1311-1312.
53. Raghuram TC, Sharma RD, Sivakumar B, et al , Effect of fenugreek

Number of
Comments
Condition Evidence/ Author,Year Statistically Magnitude Absolute Patients
Study Type Reference N Significant of Benefit Risk Needed to
Treated (Primary
or Secondary Results? (how strong Reduction Treat for
Outcome) is the effect) One
Outcome
Gupta, 2001 Improved fasting
Type 2 diabetes, Randomized, glucose & GTT
controlled, [Link] 25 Yes None NA NA
hyperlipidemia Physcians with fenugreek
double-blind seeds or diet/
study India 2001;49:
1057-1061 excercise, without
differences between
[Link] AUC
& Insulin resistance
with fenugreeK.

Type 2 diabetes Randomized, Raghuram 1994 10 Yes Large NA NA Improved

crossover study Phytother res peripheral
1994;8:83-86 glucose utilization
with fenugreek seed
supplementation

Type 2 diabetes Randomized, Sharma 1990 15 Yes Small NA NA Improvement in

crossover study [Link].1990; reported diabetic
10:731-739. symptoms.

Medium NA NA Improvement of
Type 2 diabetes Case series with Neeraja 1996 12 Yes acute glycemic
matched [Link] sci. response, most
controls Technol 1996; notable with raw
33:427-430. fenugreek seed
powder

Type 1 diabetes Randomized, Sharma1990 10 Yes Large NA NA Fasting blood

hyperlipidemia crossover study Eur [Link] Nutr. glucose levels
1990;44:301-306 and GGT
improved: serum
insulin levels
unchanged.

ANTHOCYANINS FROM BILBERRY FRUIT Green Tea Extract)

EXTRACT
EGCG inhibits cytokines responsible for destruction of
69
Vaccinium Myrtillus ( bilberry or European blue berry ) pancreatic beta cells in Type 1 diabetes . It also inhibits the
is a shruby plant that grows in Europe. The enzyme action to suppress glucose production, suppress the
anthocynosides and chlorogenic acid being the most uptake of glucose by the intestine and enhances insulin
important constituents. Bilberry has been shown to activity. It also protects from oxidative damage.
beneficially effect in micro vascular abnormalities of
65,66
diabetes . It has also been shown to improve 69 . Han Mk, “ EGCG , a constituet of Green tea , suppress cytokine
67,68 Induced pancreatic beta cells damage”. Exp. Mol. Med. 35(2);136-9, 2003.
edema and microangiopathy .
65. Scharrer A, Ober M, Anthocynosied in the treatment of retinopathies. Klin ALPHALIPOICACID
Monatsbl. Augenheikd 1981;178:386-389 (article in German)
66. Caselli L, Cllinical and electroretinographic study on acivity of anthocyanosides. Arch.
Med. Int. 1985;37:29-35 Alphalipoic acid is a potent antioxidant in both fat and water
67. Morazzoni P, Bombardelli F, Vaccnium myrillus L fitoterapia 1996; 1:3-29. soluble medium. Alpha lipoic acid can be synthesized by
68. Bontale R, Miskulin, Robert Am, pharmacological properties of myrtillus anthcyanosides; 70

correlation with results of treatment of diabetic microangiopathy. [Link] L Gabor M,

both animals and humas . It seems to be readily absorbed
Kllay F eds,flavonoids and bioflavonoids 1985, Amsterdam: ELSEVEIR 1986:193. from an oral dose and converts easily to its reduced form
Dihydrolipoic acid (DHLA) in many tissues of the body .An
EGCG ( Epigallocatechinsgallate From
 71
invitro sudy indicated that the normal mammalian CHROMIUM PICOLINATE
cells appear to be capable of taking up alpha lipoic acid
and reducing it DHLA. The effects of both ALA and A major detriment of insulin sensitivity, as it functions
DHLA are present both as intra and extracellular lipoic as a cofactor in all the insulin regulating
acid , eg. (in an oral dose). Further more its antioxidant activities75. Chromium facilitates insulin binding and
activity extends to both the oxidized form and its reduced subsequent uptake of glucose into the cell .
form . DHLA is capable of regenerating Vitamin C and
Supplemental chromium has been shown to decrease
indirectly regenerating vitamin E72, researchers have
found ALA to increase intracellular glutathione and
73 fasting glucose levels, improve glucose tolerance , lower
coenzyme q105 levels. Also appears to chelate certain insulin levels and decrease total cholesterol and
minerals74. triglycerides, while increasing HDL cholesterol in
70. Carreau JP. Biosynthesis of lipoid acid via saturated fatty acids methods enzymol.
normal , elderly and Type 2 diabetes subjects without
1979;62: 152-158 blocking insulin action76.
71. Handle man GJ, Han D, Tritscher H, Packer L, ALA reduction by mammalian cells to
the dithiol form release into culture medium. Biochem pharmacol. 1994;47: 1725-1730. Chromium picolinate has been well studied for its
72. Scholich S, Murphy ME, Sies H, Antioxidant activity of diydrolipoate against
microsomal lipid peroxidation and its dependence on alpha tocopherol. Biochem
beneficial effects on insulin resistance and diabetes. A
Biophysics. 2004 review found the mineral enhanced glucose uptake
Acta 1989; 1001:256-261.
73. Busse E , Zimmer G, Schophol B, et al Influence of ALA on intracellular and glycogen synthesis , in addition to improving insulin
lutathione invitro and invivo, ArzneimiHcl-Forschung 1992;42: 829-83 77
function .
74. Sigel H, Prijs B, Mc Cormick DB, Shih JCH, Staility of binary and ternary complexes of A 2004 clinical trial concluded chromium picolinate had
lipoate and lipoate derivatives with MN+, CU+ and ZN+ in solution. Arch. Biochem.
Biophys 1978: 187:208-214. an acute effect on the post prandial glucose metabolism
in young men, possible lowering glycemic index of a
78
meal . A 2002 trial found the mineral improved glucose
control
79
by enhancing insulin action rather than secretion .
While Israeli researchers demonstrated 200 mcg /day of
chromium picolinate balanced glucose levels and
80
reduced serum lipid levels . A result verified by dutch
researchers at an even higher dose of 1000 mcg /day.
Animal trials have shown similar results, showing
chromium picolinate supplementation can lower glucose
81
levels and improve insulin sensitivity in rats , as well as
lower fasting insulin levels and glucose disappearance
82
in hyper insulinemic .

chromium provides support for healthy glucose

metabolism and helps the body metabolize
carbohydrates and fats .
Chromium supplementation has been reported in clinical
trials for over five decades to improve insulin regulation
and glucose tolerance.* In a meta-analysis of 41 studies,
chromium was shown to significantly improve fasting
glucose and HbA1c levels in Type 2 diabetics.*49 A
meta- analysis of 11 studies found chromium
supplementation compared to placebo resulted in
significant decreases in body weight and percent body
fat.*50
75. Offenbacker Bg, Pi Sunyer Fx, Beneficial effect of chromium rich yeast on glucose
tolerance and blood lipids in elderly subjects Diabetes 1980; 29:919-25.
76. Mooradian Ad, Failla M, Hoogwer Fb, et al selected vitamins and minerals in diabetes.
Diabetes Care 1994; 17; 464-479.
77. Juturu V, Chromium and insulin resistance . Experimental Biology 2004, Abstract 351.7
78. Wenk C et al. Effects of accte chromium supplementation in post prandial metabolism in
healthy and young men . J. Am. Col. Nutr. 23, 4; 351-357, 2004.
79. Ghosh D et al, Role of Chromium supplementation in Indians withtype 2 diabetes
mellitus. J. Nutr. Biochem 13, 11, 690-697, 2002.
80 . Rabinovtz H et al Effects of chromium supplementation on blood glucose and lipid levels
in type 2 diabetes mellitus in elderly atients. Int. J. Vitamin. Nutr Res 74,3:178-82,2004.
 81. Kemi Ds, Kin TW, Kang Js, Chromium supplementation improvesinsulin sensitivity. metabolism and enhances skeletal muscle GLUT4. Translocation in Obese, hyper
J. Trace elements Med. Biol. 17, 4, 243-7, 2004. insulinemic.
82. Ce aly TW et al, Oral chromium picolinate improves carbohydrate and lipid (JCR-LA. Corpulent)rate' [Link]. 132,6:1107-14, 2002.

SELENIUM: VITAMIN D3:

Selenium is a mineral found in soil plays a key role in Vitamin D deficiency has been shown to alter insulin
Metabolism. Selenium is found to have action similar to synthesis and secretion in both humans and animal
Insulin like molecule for the down regulation of glucose models. Vitamin D supplementation improves glycemia
level. The case studies on diabetes subjects stated that: and insulin secretion in patients with Type II diabetes
Selenium treatment induces insulin like effects in with established hypovitaminosis. The mechanism of
lowering Serum glucose level and it also significantly action of Vitamin D in type II Diabetes is by mediating
decreases serum biochemical components associated not only through regulation of Plasma Calcium level,
with liver damage and lipid metabolism. Its treatment which regulates Insulin Synthesis but also through the
also reveals Apoptosis of Liver tissues. It is concluded direct action on pancreatic beta cell function.
from the clinical studies that Selenium lowers serum Palomerx :Gonzslez – Clemnte JM, B lanco- VacaF 2008 Mar,
glucose and biochemical profiles associated with liver 10(3): 185-97. Do 10.1111 (J.1463. 1326. 2007.00710
damage and lipid metabolism in diabetes.
DAEYOUN HWANG , SUJINSEO, YONGKYO KIM, Seoul National University hospital,
Seoul 110-744. Korea, Jinju 660- 758 Korea.
METHYLCOBALAMINE:
Methylcobalamine has a potential benefit in treating
MAGNESIUM: Diabetic Neuropathy. Low levels of Vitamin B 12 often
Magnesium is a chemical element and an alkaline lead to diabetic Neuropathy with high levels of blood
earth metal and most abundant ion present in the living vessels damaging compound homocysteine (Fahmy
cells and its plasma concentration is remarkably 2010). Vitamin B 12 also known as Methylcobalamine
constant in healthy subjects. Intracellular magnesium
has high affinity for nerve tissue (Mizukami 2011)
concentration is highly regulated by several factors
studies on animal models of diabetic neuropathy has
among them insulin seems to be most important. In
vitro and invivo studies have demonstrated that the found that methycobalamine may mitigate the damage
insulin may modulate the shift of magnesium from caused by diabetic. Neuropathy possibly by
extracellular to intracellular. Intracellular magnesium modulating proteinkinase'C' signaling pathways or
concentration has also been shown to be effective in activating chemical signals that helps nerve survive .
modulating insulin action (mainly oxidative glucose (Mizukami 2011, Okada- 2010, Zian'BO 2010)
metabolism), calcium related excitation concentration
coupling and decreases smoothly. From the studies it
is concluded that intracellular magnesium may play a
key role in modulating insulin-mediated glucose VITAMIN E
uptake and vascular tone. Vitamin E has been shown to reduce glycosylation of
tissues. Vitamin E enhances immunity and reduces the
MOL. Aspects Med it: 2003 feb-jun; 24(1-3); 34(52) number of infections with higher plasma vitamin E
levels. Alpha tocopherol was found to decrease both C-
reactive protein and cytokine interleukin-6 in normal
VITAMIN C
Vitamin C is known to inhibit the process of glycation to volunteers and Type 2 diabetic patients. Vitamin E
some degree, thus helping to prevent the tissue works synergistically with other nutrients to protect
Glycening effect of those AGE'S, it also improves lipid against the nerve and kidney damage.
metabolism. Vitamin C is known to inhibit the
accumilation of sorbitol, a sweet tasting alchol derived Also supplementation of Vitamin E resulted in the
from glucose, excess sorbitol is implicated in the decrease in both glucose disposal rate and number of
83
formation of cataracts in diabetic individuals and it is insulin receptors on erythrocytes . Also reported an
thought to lead to diabetic neuropathy, a cathall term that improvement in insulin sensitivity in hypertensive
means a functional disturbance or pathological change in patients.
the pheripheral nervous system. Diabetic neuropathy is
common in the early stages of Type 1 diabetes and also in
the later stages of Type 2 diabetes.
83. Skhra J, Sindelka G, Kvasnicke J, Hilgertova J, Insulin action nad fibrinolysis
influenced by Vitamin E in obese and type 2 diabetes mellitus. Diabetes Res.
Clin Pact 19994;44:27-33

VITAMIN K this vitamin are rare it is included for good measure because
Vitamin K in the form of phylloquinone, the form found Japanese researchers have found that it can help improve
in plants and leafy vegetables, although deficiencies of insulin sensitivity and blood sugar regulation.
VANADIUM ISOLEUCINE:
Prior to the discovery of insulin in 1922, vanadium was Isoleucine is a approved neutraceutical and it is essential
used for the control of blood sugar. Two small studies branched chain aliphatic amino acid found in many
(one with six type 2 diabetic patients , one with seven proteins. It is important in hemoglobin synthesis and
Type 2 diabetes patients) have confirmed the regulation of blood sugar and energy levels. Clinical
effectiveness of vanadyl sulphate in improving insulin studies on normal and diabetic subjects concluded that
84,85
sensitivity . the both acute and chronic treatment with isoleucine is
beneficial for glucose metabolism and glucose
Vanadium has also shown some overall blood glucose intolerance
86
lowering ability . As well as an ability to effectively .
control altered glucose metabolism and antioxidant Isoleucine is a branched-chain amino acid. Like exercise,
87 isoleucine has been shown to enhance uptake of glucose
status in diabetic rat lenses . 90
by skeletal muscles and decreases glucose production in
the liver. Branched-chain amino acids can also help
84. Cohen N, Halberstan m, Shlimovich P et al , oral vanadyl sulphate improves hepatic
and peripheral insulin sensitivity in patients with NIDDM. J. of Clin. Invest reduce fatigue during exercise.
1995;95: 2501-2509
85. Halberstem M, Cohen N, Schlimovich Ch P, et al oral vanadyl sulphate improves
Biol Pharm 2008 Mari 31(3);; 469-72 I kehara, Kawajaki N, Mac Zonok
insulin sensitivity in NIDDM but not in obese non diabetic subjects.
Diabetes 1996; 45: 659-666.
86. Sakurai H. “ A new concept; the use of vanadium complexes in the treatment GLYCINE:
of diabetes mellitus'. Chem Res 2, 4; 237-48 , 2002.
87. Preet A, et al “ efficacy of lower doses of vanadiumin restoring altered glucose Glycine is an amino acid. This is shown to stimulate
metabolism and antioxidant status in diabetic rat lenses “ J. secretion and decrease glycated hemoglobin in Type II
Bio Sci. 30,2:221-30, 2005.
diabetes. Treatment with glycine is likely to have a
BIOTIN beneficial effect on innate and and adaptive immune
Biotin helps to lower post prandial glucose levels, responses and may help prevent tissue damage caused
improved response to a glucose load & decreased insulin by chronic inflammation in patients with Type II
88
resistance .This vitamin has demonstrated an ability diabetes. It has been shown to increase adiponectin,
to improve glucose metabolism in human dialysis with which can down- regulate inflammatory cytokines in fat
Type 2 diabetes89. tissue, thus helping to modulate inflammation associated
91
with obesity and MetS.*
88. Reddi A, De Angelis B, Frank O, [Link]., Biotin supplements when improves glucose &
insulin tolerance in generally diabetic kk Mice. Life Sci kgg ; 42; 1323-1330.
Cruz, M; Maldonada-Bernal, R; Wacher, N H; Carvajal -2008
89. Icoutsikos, D, Fourtounas C, kapetanaki A, [Link], oral glucose tolerance test after high Biochemistry Medical Research Uni, Hospital de Especialidades, Mexico City
dose i.v. biotin administration is normoglucemic hemodialysis patients.
[Link]. 1996;18:131-137.
ACETYL CYSTEINE
An essential supplement in the case of patients with
Type 2 and Type 1 diabetes. An amino acid derivative
that is converted into glutathione, the body's master
antioxidant, the most vital of all such molecules. The
role of glutathione are too numerous to list, but it is
worth noting that it can help prevent some of the
complications of diabetes. NAC decreases plasma
soluble vascular cell
BENFOTAMINE: adhesion molecule-1 in NIDDM . Overtime this can
92

It is a fat soluble derivative of thiamine that is more significantly decrease the progression of vascular
readly absorbed by digestive tract (SancheZ - RamireZ damage that occurs with diabetics. It also helps to
2006). It modulates several pathways that contributes to protect the integrity of erythrocytes and reduces
Diabetic Neuropathy: The Formation of AGEs, the structural changes in the Type 2 diabetics / NAC may
proteinkinase 'C' pathways and damaging changes that also reduce the glycation process that lead to cataract
occurs within cells due to high glucose level ( Varkonyi 93
formation .
2008, Balakumar 2010). It also helps to prevents
vascular problem.
(Stracke 2008). It improves carbohydrate and amino acid
metabolism to produce cellular energy. It has found to be 92. De mattia G, Bravi MC, et al reduction of oxidative stress by oral N-acetyl cysteine
neuro and nephroprotective in situations associated with treatment decreases plasma vascular cell adhesion molecule -1, concentrations in non
elevated blood sugar. obese, non dyslipidemic, normotensive patients with NIDDM,
Diabetolgiab 1998 NOV.; 41(11):1392-136.
93. Straface E, Rivabene R, Masella R, et al structural changes of the erythrocyte as a
marker of NIDDM; protective effects of NAC. Biochem Biophy. Res.
Commun 2002 Feb 8; 290(5),1393-98.
CONCLUSION & FUTURE DIRECTION ORTHOMOLECULAR MEDICINE:
The incidence of Type 2 diabetes is increasing VISIONARY SCIENCE
dramatically worldwide, resulting in large measure form
the increasing prevalence of obesity94. In addition In 1968, the Noble Prize-winning scientist Linus
research is uncovering the importance of
“Pre-diabetic” state or Pauling, PhD, Published an article in the journal Science
metabolic syndrome , when insulin resistance gives rise describing “orthomolecular” approach to illness. This
was the first time that such an approach was presented to
to
impairment of glucose Unfortunately, varying
the public specifying that the
“ concentration of substances
metabolism95,96.
Patients who have metabolic syndrome or diabetes are at normally present in the human body may control mental
greatly increased
95,96 risk of cardiovascular morbidity and disease” Dr. Pauling later extended this strategy beyond
mortality . Thus, Insulike approach can modulate mental
6
. illness to include the discipline of orthomolecular
glucose homeostasis and potentially improve lipid medicine.
parameters would be desirable. This is especially true
for diabetes prevention in patients with metabolic Orthomolecular medicine is a paradigm that attempts to
prevent and treat disease by integrating conventional
syndrome. These patients already manifest medicine therapies with vitamins, phytonutrients, and
abnormalities of glucose handling and could be relief other dietary micronutrients.
from a low-risk, in expressive, food based intervention
aimed at normalizing their metabolic milley. Insulike as NUTRIGENOMICS: GUIDING GENETIC
a dietary supplement that may hold promise in this DESTINY
regard. The data generated to date are sparse but will
Driven by the recent technological breakthroughs
hopefullyhelp to the development of well designed
associated with the mapping of the genome, the science
adequatly powered, randomized, clinical trials
of nutrigenomics holds great potential for predicting how
evaluating the effect of Insulike on measures of insulin
specific nutrients and dietary ingredients can directly
resistances, insulin secretion, insulin binding, sensitivity
affect the disease by specific genetic
glucose absorption & cholesterol metabolism.
interactions9,10.
94. Yale JF. Prevention of type 2 diabetes, Int., [Link] [Link]. 2000;113:35-39.
Nutrigenomics holds promise in advancing the goal of
95. No authors liked (Adult treatement grand III) JAMA 2001;285:2486 -2497.
preventing diseases with “individualized nutrition” based
on unique genetic needs.
96. Ford Es, Giles WH, Dietz WH, Prevalance of the metabolic syndrome Among
US adults ; Frdihps from the third National Health & Nutrition exultations survey. Currently, however, nutrigenomics remains a very
JAMA 2002 ; 287:356-359.
young and developing science that has not yet developed
PHENOTYPIC NUTRITION A NEW to the potential of being able to offer broad-based
STRATEGY FOR PREVENTING METABOLIC nutrient-gene
SYNDROME testing of this sort.
A powerful strategy called phenotypic nutrition can help There is, however, another approach that we can use for
modulate the expression of your unique code, thus specific, individualized nutrient recommendations that
dramatically reducing your risk of developing disease. incorporate Dr. Pauling's visionary approach to
Phenotypic nutrition uses specific nutrients with the
biochemical and genetic effects to help protect you from orthomolecular medicine. This alternative approach is
disease. called phenotypic nutrition.
One of the most important threats to your health and
longevity is metabolic syndrome, a disorder little known
to the fast becoming an extremely important public
health issue. This deadly, common condition affects
approximately one in five people overall, with even
higher rates among certain ethnic groups1.
By applying a phenotypic nutrition strategy, we can help
to guard against the deadly dangers of cardiovascular
disease associated with metabolic syndrome.
GENES, GENOTYPE, AND PHENOTYPE your phenotype.

Your unique genetic code defines your genotype. The While it is not known exactly which genes are responsible for
expression of your individual genetic code is your the constellation of abnormalities associated with metabolism
phenotype. Your genes and your environment influence syndrome, a number of genes so far identified play a role in
the malfunction associated with abnormally elevated
With phenotypic nutrition, once high-risk individuals
plasma glucose97.
have been identified strategies that include dietary
Metabolic syndrome is a phenotypic expression of the modifications and supplementation of specific
genetic code as it interacts with the environment. nutraceuticals can be implemented to help decrease
Specifically, have a genetic tendency to develop the disease risk.
metabolic syndrome phenotype, you will be far more Identifying Those Most AT Risk
likely to develop this phenotype if you are overweight,
do not exercise, consume a diet high in simple sugars Metabolic syndrome is characterized by insulin
and saturated fats, and do not consume specific nutrients resistance. Identifying individuals with evidence of
insulin resistance the development of full-blown
with beneficial nutrient-gene interactions. metabolic syndrome allows us to intervene with a
nutrient and lifestyle strategy to prevent progression of
In 2004, an innovative approach to weight management this condition.
and obesity was published in the peer-reviewed journal
Curr. Ther. Targets. This approach called “ Thankfully, simple metabolic markers are very useful in
nutriphenotypic,” is selective nutrition based on an helping to identify individuals with insulin resistance
who are risk of cardiovascular disease.
individual's phenotypic metabolic characterstics98.
Triglycerides, Insulin, and HDL. Clinical studies
This past year, researchers described the concept of a
suggest that the following Threshold values for
“nutritional phenotype” that characterizes the plasma triglycerides ratio of triglycerides to HDL, and
relationship of biochemical measures, metabolic fasting insulin are the most useful metabolic markers in
parameters, and functional characteristics (for example, identifying insulin-resistant individuals at risk of
100
exercise, body weight, example to environmental cardiovascular disease .
pollutants and toxins, emotional stress) on health. The
Triglycerides greater than or equal to 130 mg/dL,
nutrient phenotype is a function of genes, disease Triglycrides/HDLratio greater than or equal to 3.0,
Fasting insulin level greater than or equal to 15
µU/mL, C-reactive protein

Moreover, research has demonstrated that a condition of

low-grade systemic inflammation is associated with
insulin resistance. For example, a recent clinical study
showed that insulin and insulin resistance remained
significantly and independently related to C-reactive
protein (CRP) levels, a marker of inflammation, after
adjustments for age, sex , body mass index, waist size,
alcohol consumption, level of physical activity, and
smoking habits101. Another clinical study that CRP was
. pathways to help prevent disease and achieve optimal health
environment, and
The nutriphenotypic/nutrient
behavior
99 phenotype approach and longevity.
represents an integrative strategy to help prevent
and treat disease just as specific inputs to a
computer will cause specific outputs,
phenotypic
nutrition uses specific nutrients for specific
effects.
J Nutr.2005 Jul;135(7):1613-6.

Phenotypic nutrition affects the expression of your

genes and unique biochemistry so that you can
influence your genetic destiny. Instead of dooming
individuals to disease and an early demise due to “bad
genes,” phenotypic nutrition uses nutrients that act on
specific genes as well as biochemical and molecular
 102
significantly correlated to insulin resistance . multicenter, p controlled trial, type II diabetes patients
LIPOICACID treated with lipoic acid demonstrated a significant
A naturally occurring nutrient, lipoic acid is increase in insulin-stimulate glucose disposal104.
known to improve glucose metabolism by Furthermore, lipoic acid's molecular attributes include
influencing genetic transcriptior factors in fat cells increasing glucose uptake through recruit the glucose
through the mitogen- activated protein kinase transporter-4 (GLUT-4) to plasma membranes, a
(MARK) pathway .
103
For example, in a mechanism that is shared with insulin-stimulated glucose
uptake105.
Research also shows that lipoic acid decreases markers smoking status and physical activity they found that
of vascular inflammation in metabolic syndrome. A individuals with metabolic syndrome had significantly lower
concentrations of retinyl esters, Vitamin C and carotenoids
recent randomized, double-blind clinical trial showed 111
except lycopene .
that after four weeks of therapy, endothelium-
dependent vasodilatation of bronchial artery was
increased by 67%,44%, and 75% in groups receiving
irbesartan (an angiotensin-blocking drug), lipoic acid,
and irbesartan plus lipoic acid, respectively, compared
to placebo. Furthermore, treatment with irbesartan and
lipoic acid was associated with statistically significant
reductions in plasma levels of pro-inflammatory
106
mediators such as interleukin .

BIOFLAVONOIDS GREEN TEA EXTRACT

Inflammation and associated insulin resistance play a
critical role in the development of metabolic syndrome
107,108
and Type of diabetes . Nutrients that act to down-
regulate genes involved in inflammation are critical to
preventing metabolic syndrome.

TOCOPHEROLS

Vitamin E is an important nutrient in preventing

metabolic syndrome, as it helps regulate several genes
109
affecting cardiovascular disease risk .

Genes that are associated with lipid uptake and

Atherosclerosis (CD36, SR-BI, and SR-AI) Genes that
are related to inflammation, Cell adhesion, and platelet
aggregation( E- Selection, ICAM- 1 , integrins,
glycoprotein IIb, IL-2, IL-4, and IL-beta).

Furthermore the appropriate genetic regulation of

glucose transport protein (GLUT-3) is critical to optimal
blood glucose control. Studies have shown that both
aging and vitamin E deficiency are associated with
110
decreased expression of Glut- 3 .

VITAMIN C

Using data from the Third National Health and Nutrition

Examination Survey (1988-1994), researchers evaluated
the levels of vitamins A and C, retinyl esters, five
carotenoids and other trace nutrients in 8,808 US adults
aged 20 and older without metabolic syndrome. After
adjusting for factors like age, sex, ethnicity, education
CINNAMON EXTRACTS nuclear magnetic resonance and mass spectroscopy114.

In clinical trials, cinnamon has demonstrated The polyphenol Type-A polymers from cinnamon up-
remarkable effects on glucose control. regulate expression of genes involved in activation of
(phosphorylation) the insulin receptor and increase
In 2003, a placebo-controlled study of Type 2 glucose uptake in cell studies115. In other
diabetes patients who were given one, three, or six cinnamon polyphenol such as methylhydroxychalcone
116
grams a day of cinnamon placebo showed that have been shown to be potent insulin mimics .
after 40 days, all three levels of cinnamon reduced
mean fasting serum glucose by 18-29%, BLUE BERRYEXTRACT
Triglycerides by 23-30%, LDL by 7-27%, and
Total Cholesterol by 12-26%. No significant Clinical studies have shown that chlorogenic acid delays
112
changes were noted in the other groups . glucose absorption and improves gastrointestinal
hormone secretion.
Cinnamon also has been shown to have excellent
antioxidant properties. Natural water-soluble The association between chlorogenic acid and GLP-1 is
cinnamon extract (as in Insulike Tablets) has particularly remarkable. Several GLP-1 related
shown to inhibit oxidation by 88%, while a pharmaceutical agents are mimicking this hormone as a
synthetic antioxidant control, butylated treatment for Type II diabetes mellitus, including the
hydroxytoluene, inhibited oxidation 80%113. recently FDA-Approved analog BYETTATM
(exenatide). Chlorogenic acid acts to increase GLP-1 and
Water-soluble polyphenol polymers (polyphenol delay glucose absorption, thereby maintain the
type-A polymers) from cinnamon increase insulin- responsiveness of the insulin-producing beta cells of the
117
dependent glucose metabolism in vitro. These pancreas .
polymers have recently been characterized by
Lactonova goes a step further to steer patients function when compared to a high-glycemic index diet and
120
toward low-carbohydrate foods and away from common exercise .
food allergens that can contribute to inflammation. In addition to nutritional and dietary interventions, prevention
and correction of MetS should focus on increasing fitness
levels for all age groups (see Metabolic Syndrome Patient
Benefits of Exercise & Stress Guide for specific exercise tips).

Management Exercise Reducing Stress

There is a strong connection between elevated cortisol levels
The benefits of exercise are well known and accepted. and elevated blood sugar, hyperinsulinemia, and obesity.
In weight-loss programs exercise enhances maintenance Exercise is a good way to reduce the effects of stress. Yoga
121
of lean muscle mass. Lean muscle tissue assists in exercise, for instance, can decrease salivary cortisol levels ,
utilization of glucose and improves fatty acid increase GABA (an inhibitory neurotransmitter involved in
metabolism. Citation of several studies helps illustrate relaxation), and result in improvements in mood and anxiety.
specific benefits. For example, a 12-week exercise In one study, both 60- minute yoga and 60-minute walking
regimen consisting of 80 minutes of mixed aerobic and were shown to improve GABA levels, as well as feelings of
resistance training three days a week by Korean college anxiety, although yoga was more effective than walking .
122

students resulted in a significant reduction in percent

118
body fat, waist circumference, and blood pressure .
Exercise by older adults with metabolic syndrome had a
positive effect on blood pressure, Triglycerides, HDL-
cholesterol levels, Waist Circumference, body
composition, aerobic fitness, and insulin resistance. The
participants exercised 60 minutes a day, five days a
week, regardless of whether they were following a high-
119
or low- glycemic index diet .
Other studies illustrate the benefit of coupling exercise
with dietary modifications. Research on pre-diabetics
found a low-glycemic index diet partnered with exercise
adds additional protection by lowering postprandial
hyperinsulinemia and preserving pancreatic beta-cell
Although cortisol can become elevated during o k i n e t i c a n d pharmacodynamic properties of a
periods of extreme exercise (such as marathons), drug in such a way that its utility is maximized, side
jogging can result in a decrease in stress effects are reduced and cure or control of the condition
hormones. One study of 18- to 20-year old is achieved, in the shortest possible time by using
females found 50 minutes of jogging five days per smallest quantity of drug administered by the most
week resulted in decreased urinary output of the suitable route. Slow release drug formulations have
stress hormones epinephrine and cortisol. Jogging become more important in therapy as a means of
123
also resulted in improvements in depression . reduced dosing frequency, hence potentially
improving patient compliance and consequently
efficacy. The efficient benefits of slow release
Testing formulation include.
Salivary
 Decreased dose frequency
 Reduced peak to through ratio of drug in
Cortisol
systemic circulation
 Reduced rate of rise of drug concentration in
Levels
blood
Salivary cortisol is a reliable and simple means to assess
 Sustained and consistent blood level with in the
cortisol levels in patients, and the kits can be
therapeutic window
provided by many labs. The test requires merely
 Enhanced bioavailability
that a patient collect saliva in a test tube four
 Reduced side effects
times daily – At 8 AM, noon, 4 PM, and 11 PM.
 Improved patient compliance
The samples are mailed back to the lab. Other -Dusane Abhijit Ratilal et al/ IJRAP 2011, 2(6) 1701-1708
hormones, such as DHEA, Testosterone, and [Link], 2010, 2(1): 349-360

Estrogens, can be measured in this way as well.

CONCLUSION
BENEFITS OF SLOW RELEASE
FORMULATIONS: Phenotypic Nutrition enables you to choose dietary
Slow release drug delivery system optimizes strategies and nutrients that influence powerful
the b i o p h a r m a c e u t i c a l , p h a r m a c biochemical and factors to help control the expression of
your genetic code to your benefit.
References: Eugenia jambolana seeds on streptozotocin induced diabetic rats. Food Chem Toxicol 2008;46:2376-2383.
32. Tanwar RS, Sharma SB, Singh UR, et al. Antiatherosclerotic potential of active principle isolated from Eugenia jambolana
1. Ervin RB. Prevalence of metabolic syndrome among adults 20 years of age and over, by sex, age, race and in streptozotocin-induced diabetic rats. Evid Based Complement Altern Med 2011;2011:127641.
ethnicity, and body mass index: United States, 2003-2006. Natl Health Stat Report 2009;13:1-7. 33. Alappat L, Awad AB. Curcumin and obesity: evidence and mechanisms. Nutr Rev 2010;68:729-738.
2. [Link] [Accessed October, 25, 2012] 34. Aggarwal BB. Targeting inflammation-induced obesity and metabolic diseases by curcumin and other
3. [Link] Med. Assoi. 2002 Mar ; 100(3): 144-8. nutraceuticals. Annu Rev Nutr 2010;30:173-199.
4. Diabetes 1996 Vital Statastics. Alexandria, VA: American Diabetes Association. 35. Taniguchi S, Asano N, Tomino F, Miwa I. Potentiation of glucose induced insulin secretion by fagomine, a pseudo
5. No Authors listed. Report of the Expert Committee on the Diagnosis and Classification of Diabetes sugar isolated from mulberry leaves. Horm. Metab. Res. 1998 ;30:679-683
Melllitus. Diabetes Care 1997;20:1183-1191. 36. J. Nutr 2005; 135: 729-734, Clin. Chem Acta 2004; 348: 215-218, Clin Chem Acta 2001; 314: 47-53
6. Calvin AD, Albuquerque FN, Lopez-Jimenez F, Somers VK. Obstructive sleep apnea, inflammation, and the 37. Int. J. of Food sci. And Nutr, taylao and Francis ltd, 2003;54:411-416.
metabolic syndrome. Metab Syndr Relat Disord 2009;7:271-278. 38. Diabetes care in press, published online Feb 15 2007.
7. Sharpless JL. Polycystic ovary syndrome and the metabolic syndrome. Clin Diabetes 2003;21:154-161. 39. Liu.F, im J, Lin X, Chen X, [Link] 2001, sep; 131(9):2242-7
8. Emanuela F, Grazia M, Marco de R, et al. Inflammation as a link between obesity and metabolic syndrome. 40. Suzuki Y, Unno T, Leshitani M, Hayashi K, Kakuda T. J. Nutr. Sci. Vitaminology(Tokyo)1999Dec; 45(6);791-
J Nutr Metab 2012;2012:476380. 795.
9. Weglicki WB. Hypomagnesemia and inflammation: clinical and basic aspects. Annu Rev Nutr 2012;32:55-71. 41. Hayashi T, et al Planta med 2002; Feb68(2), 173-5
10. Nadler JL, Buchanan T, Natarajan R, et al. Magnesium deficiency produces insulin resistance and increased 42. Kakunda T, SakaneL, Takihara T, Ozaki Y, Takeuchi H, Kuroyanagi M,Biosci. Biotechnology Biochem 1996 Feb;
thromboxane synthesis. Hypertension 1993;21:1024-1029. 60(2)204-8.
11. He K, Liu K, Daviglus ML, et al. Magnesium intake and incidence of metabolic syndrome among young adults. 43. Murakami L, Myozak, Kasai R, Ohtani K, KurokawaT, Ighibasis, Dayrit F,Padolina WG, Yamasaki K. chem., Pharm bull
Circulation 2006;113:1675-1682. (Tokyo) 1993, DEC; 41(12): 2129-31.43) Hattori K, et al activation of lagerstroemeia Speciosa has insulin like activity.
12. Chung JH, Yum KS. Correlation of hair mineral concentrations with insulin resistance in Korean males. Biol [Link] Sci. 93,1:69-73-2003
Trace Elem Res 2012;150:26-30. 44. Impart rodosevich J, Deas S. Polansky, MM Beedke DA, IngerbrustenTS Anderson RA, graves Dj; regulation of
13. Sung CC, Liao MT, Lu KC, et al. Role of vitamin D in insulin resistance. J Biomed Biotechnol phosphorylase phophatase (PTP-1) and insulin receptor kinase by fractions from cinnamon ; implications from Cinnamon
2012;2012:634195. regulation of insulin signaling. Horm res 50; 177-182, 1998.
14. Parker J, Hashmi O, Dutton D, et al. Levels of vitamin D and cardiometabolic disorders: systematic review and 45. Jarvill-Taylor KJ, andrson RA, Graves Dj, A ydroxychalcon derived from cinnamon functions as a mimetic for insulin in
meta-analysis. Maturitas 2010;65:225-236. 3T3-L1 adipocytes. J AM. Coll. Nutr 20 ; 327-336, 2001. Coll. Nutr 20 ; 327-336, 2001.
15. Vincent J. The biochemistry of chromium. J Nutr 2000;130:715-718. 46. Broadhust CL, Schmidt WS, Anderson RA, et al. Lipids, chromium and phytochemicals: a synergistic approach to
16. Mattei J, Malik V, Hu FB, et al. Substituting homemade fruit juice for sugar-sweetened beverages is associated NIDDM. Essential fatty acids and eicosanoids; Invited papers from the fourth conference July 1997. Prostaglandins leukot
with lower odds of metabolic syndrome among Hispanic adults. J Nutr 2012;142:1081-1087. Essent Fatty acids 1997: 57:2002
17. Nettleton JA, Lutsey PL, Wang Y, et al. Diet soda intake and risk of incident metabolic syndrome and type 2 47. Chem Pharm Bull1986; 34: 633-642.
diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA). Diabetes Care 2009;32:688-694. 48. Journal of American college of Nutrition, Vol. 20, No.4, 327 -336(2001)
18. Bocarsly ME, Powell ES, Avena NM, et al. High-fructose corn syrup causes characteristics of obesity in rats: 49. Qin B, Panickar KS, Anderson RA. Cinnamon: potential role in the prevention of insulin resistance, metabolic syndrome,
increased body weight, body fat and triglyceride levels. Pharmacol Biochem Behav 2010;97:101-106. and type 2 diabetes. J Diabetes Sci Technol 2010;4:685-693.
19. Stanhope KL, Havel PJ. Endocrine and metabolic effects of consuming beverages sweetened with 50. Stoecker BJ, Zhan Z, Luo R, et al. Cinnamon lowers blood glucose in hyperglycemic subjects. FASEB J 2010;24 [Meeting
fructose, glucose, sucrose, or high-fructose corn syrup. Am J Clin Nutr 2008;88:1733S-1737S. Abstract Supplement 722.1]
20. Parker K, Salas M, Nwosu VC. High fructose corn syrup: production, uses, public health concerns. 51. Doi M, Yamaoka I, Nakayama M, et al. Isoleucine, a blood-glucose lowering amino acid, increases glucose uptake by
Biotechnol Mol Biol Rev 2010;5:71-78. rat skeletal muscle in the absence of increases of AMP-activated protein kinase activity. J Nutr 2005;135:2103-2108.
21. Lutsey PL, Steffen LM, Stevens J. Dietary intake and the development of the metabolic syndrome: the 52. Savaire Y, Petit P, Broca C, et al 4-hydroxy isoleucine ; a novel amino acid, potentiator of insulin secretion. Diabetes
Atherosclerosis Risk in Communities study. Circulation 2008;117:754-761 1998; 47:206-210.
22. Golbidi S, Mesdaghinia A, Laher I. Exercise in the metabolic syndrome. Oxid Med Cell Longev 53. Raghuram TC, Sharma RD, Sivakumar B, et al , Effect of fenugreek seeds on intravenous glucose disposition in non insulin
2012;2012:349710. dependant diabetic patients. Phytother. Res 1994; 8: 83-86
23. Neto A, Sasaki J, Mascarenhas L, et al. Physical activity, cardiorespiratory fitness, and metabolic syndrome. 54. Ajabnoor MA, Tilmisany Ak. Effect of trigonella foeum graceum on blood glucose levels in normal and alloxin diabetic
BMC Public Health 2011;11:674-680. mice J. Ethno pharmacol 1988;22 : 45-49.
24. Casals-Casas C, Desvergne B. Endocrine disruptors: from endocrine to metabolic disruption. Annu Rev Physiol 55. Amin R, Abdul Ghani As, Shleiman MS. Effect of trigonella foeum gracecum on intestinal absorption. Proc. Of the 47 th
2011;73:135-162. annual meeting of the American diabetes association9Indiana polis USA) Diabetes 1987; 36:2119.
25. Alonso-Magdalena P, Ropero A, Soriano S, et al. Bisphenol-A acts as a potent estrogen via non-classical estrogen 56. Stark, Madar Z, The effect of an ethanol extract derived fenugreek on bile acid absorption and cholesterol levels. Br. J. Nutr.
triggered pathways. Mol Cell Endocrinol 2012;355:201-207. 1993;69:277-287.
26. Alonso-Magdalena P, Ropero A, Soriano S, et al. Bisphenol-A: a new diabetogenic factor? Hormones 57. Petit P, sauvaire Y, Ponsin G, et al effects of fenugreek seed extract on feeding behaviour. Metabolic-endocrine
2010;9:118-126. [Link] Biochem Behav 1993; 45; 369-374.
27. Chandola T, Brunner E, Marmot M. Chronic stress at work and the metabolic syndrome: prospective study. 58. Al. Habori, Al Agubari Am, Al-Mamery M. Effects of fenugreek seeds and its extracts on plasma lipid profile. Phytother
BMJ 2006;332:521-525. Res1998;12 : 572-575.
28. Martins Mdo C, Lima Faleiro L, Fonseca A. Relationship between leptin and body mass and metabolic syndrome 59. Al- Habori M, Raman A. Antidiabetic andhypocholesterolaemic effects of fenugreek. Phytother Res
in an adult population. Rev Port Cardiol 2012;31:711-719. 1998;12:237-242.
29. Chen SJ, Yen CH, Huang YC, et al. Relationships between inflammation, adiponectin, and oxidative stress in 60. Valette G, Sauvaire Y, Baccao JC, Ribes G; Hypocholesterolaemic effect of fenugreek seeds. Atherosclerosis
metabolic syndrome. PLoS One 2012;7:e45693 1984;50;105-111.
30. American Diabetes Association. Clinical practice recommendations 1995. Position statement: diabetes mellitus 61. Sauvaire Y, Ribes G, Baccao JCet al . Implication of steroid saponins and sapogenins in the
and [Link] Care 1995; 18:28. hypocholesterolaemic effect offenugreek. Lipids 1991; 26;191-197.
31. Sharma B, Balomajumder C, Roy P. Hypoglycemic and hypolipidemic effects of flavonoid rich extract from 62. Varshney Ip, sharma SC, saponins and sapogenins ; Part xxxii. Studies on trigonella foenum graceum linn. Seeds. J. Indian
 Chem Soc 1966;43:564-567.
63. Sidhu GS, Oakenfull Dg, A mechanism for the hypocholesterolaemic activity of saponins. Br.J. 67. Morazzoni P, Bombardelli F, Vaccnium myrillus L fitoterapia 1996; 1:3-29.
Nutr. 1986;55:643-649 68. Bontale R, Miskulin, Robert Am, pharmacological properties of myrtillus anthcyanosides; correlation with
64. Mishkinsy J Joseph , Sulman Fg, Hypoglycemic effect of trionella : Lancet 1967; 2:1311-1312. results of treatment of diabetic microangiopathy. [Link] L Gabor M, Kllay F eds,flavonoids and
65. Scharrer A, Ober M, Anthocynosied in the treatment of retinopathies. Klin Monatsbl. Augenheikd bioflavonoids 1985, Amsterdam: ELSEVEIR 1986:193.
1981;178: 386-389 (article in German) 69. Han Mk, “ EGCG , a constituet of Green tea , suppress cytokine Induced pancreatic beta cells damage”. Exp.
66. Caselli L, Cllinical and electroretinographic study on acivity of anthocyanosides. Arch. Med. Int. 1985;37:29-35 Mol. Med.35(2);136-9, 2003.
70. Carreau JP. Biosynthesis of lipoid acid via saturated fatty acids methods enzymol. 1979;62: 152-158
71. Handle man GJ, Han D, Tritscher H, Packer L, ALA reduction by mammalian cells to the dithiol form release
into culture medium. Biochem pharmacol. 1994;47: 1725-1730.
72. Scholich S, Murphy ME, Sies H, Antioxidant activity of diydrolipoate against microsomal lipid peroxidation and
its dependence on alpha tocopherol. Biochem Biophysics. Acta 1989; 1001:256-261.
73. Busse E , Zimmer G, Schophol B, et al Influence of ALA on intracellular lutathione invitro and invivo,
ArzneimiHcl-Forschung 1992;42: 829-83
74. Sigel H, Prijs B, Mc Cormick DB, Shih JCH, Staility of binary and ternary complexes of lipoate and lipoate
derivatives with MN+, CU+ and ZN+ in solution. Arch. Biochem. Biophys 1978: 187:208-214.
75. Offenbacker Bg, Pi Sunyer Fx, Beneficial effect of chromium rich yeast on glucose tolerance and blood lipids
in elderly subjects Diabetes 1980; 29:919-25.
76. Mooradian Ad, Failla M, Hoogwer Fb, et al selected vitamins and minerals in diabetes. Diabetes Care 1994; 17;
464-479.
77. Juturu V, Chromium and insulin resistance . Experimental Biology 2004, Abstract 351.7
78. Wenk C et al. Effects of accte chromium supplementation in post prandial metabolism in healthy and young men
J. Am. Col. Nutr. 23, 4; 351-357, 2004.
79. Ghosh D et al, Role of Chromium supplementation in Indians withtype 2 diabetes mellitus. J. Nutr.
Biochem13, 1, 690-697, 2002.
80. Rabinovtz H et al Effects of chromium supplementation on blood glucose and lipid levels in type 2 diabetes
mellitus in elderly atients. Int. J. Vitamin. Nutr Res 74,3:178-82,2004.
81. Kemi Ds, Kin TW, Kang Js, Chromium supplementation improvesinsulin sensitivity. J. Trace elements Med.
Biol. 17, 4, 243-7, 2004.
82. Ce aly TW et al, Oral chromium picolinate improves carbohydrate and lipid metabolism and enhances skeletal
muscle GLUT4. Translocation in Obese, hyper insulinemic. (JCR-LA. Corpulent)rate' [Link]. 132,6:
1107-14, 2002.
83. Skhra J, Sindelka G, Kvasnicke J, Hilgertova J, Insulin action nad fibrinolysis influenced by Vitamin E in obese
and type 2 diabetes mellitus. Diabetes Res. Clin Pact 19994;44:27-33
84. Cohen N, Halberstan m, Shlimovich P et al , oral vanadyl sulphate improves hepatic and peripheral insulin
sensitivity in patients with NIDDM. J. of Clin. Invest 1995;95: 2501-2509
85. Halberstem M, Cohen N, Schlimovich Ch P, et al oral vanadyl sulphate improves insulin sensitivity in NIDDM
but not in obese non diabetic subjects. Diabetes 1996; 45: 659-666.
86. Sakurai H. “ A new concept; the use of vanadium complexes in the treatment of diabetes
mellitus'. Chem Res 2, 4; 237-48 , 2002.
87. Preet A, et al “ efficacy of lower doses of vanadiumin restoring altered glucose metabolism and
antioxidant status in diabetic rat lenses “ J. Bio Sci. 30,2:221-30, 2005.
88. Reddi A, De Angelis B, Frank O, [Link]., Biotin supplements when improves glucose & insulin tolerance in
generally diabetic kk Mice. Life Sci kgg ; 42; 1323-1330.
89. Icoutsikos, D, Fourtounas C, kapetanaki A, [Link], oral glucose tolerance test after high dose i.v. biotin
administration is normoglucemic hemodialysis patients. [Link]. 1996;18:131-137.
90. Doi M, Yamaoka I, Nakayma M, et al. Hypoglycemic effect of isoleucine involves increased muscle glucose
uptake and whole body glucose oxidation and decreased hepatic gluconeogenesis. Am J Physiol Endocrinol
Metab 2007;292: E1683-E1693.
91. Alarcon-Aguilar FJ, Almanza-Perez J, Blancas G, et al. Glycine regulates the production of pro-inflammatory
cytokines in lean and monosodium glutamate-obese mice. Eur J Pharmacol 2008;599:152-158.
92. De mattia G, Bravi MC, et al reduction of oxidative stress by oral N-acetyl cysteine treatment decreases plasma
vascular cell adhesion molecule -1, concentrations in non obese, non dyslipidemic, normotensive patients with
NIDDM, Diabetolgiab 1998 NOV.; 41(11):1392-136.
93. Straface E, Rivabene R, Masella R, et al structural changes of the erythrocyte as a marker of NIDDM; protective
effects of NAC. Biochem Biophy. Res. Commun 2002 Feb 8; 290(5),1393-98.
94. Yale JF. Prevention of type 2 diabetes, Int., [Link] [Link]. 2000;113:35-39.
95. No authors liked (Adult treatement grand III) JAMA 2001;285:2486 -2497.
96. Ford Es, Giles WH, Dietz WH, Prevalance of the metabolic syndrome Among US adults ; Frdihps from the
third National Health & Nutrition exultations survey. JAMA 2002 ; 287:356-359.
97. Ha CH, So WY. Effects of combined exercise training on body composition and metabolic syndrome factors.
Iran J Public Health 2012;41:20-26.
98. Malin SK, Niemi N, Solomon TP, et al. Exercise training with weight loss and either a high- or low-glycemic
index diet reduces metabolic syndrome severity in older adults. Ann Nutr Metab 2012;61:135-141.
99. Solomon TP, Haus JM, Kelly KR, et al. A low-glycemic index diet combined with exercise reduces insulin
resistance, postprandial hyperinsulinemia, and glucose-dependent insulinotropic polypeptide responses in obese,
prediabetic humans. Am J Clin Nutr 2010;92:1359-1368.
100. Smith JA, Greer T, Sheets T, Watson S. Is there more to yoga than exercise? Altern Ther Health
Med 2011;17:22-29.
101. Streeter CC, Whitfield TH, Owen L, et al. Effects of yoga versus walking on mood, anxiety, and brain GABA
levels: a randomized controlled MRS study. J Altern Complement Med 2010;16:1145-1152.
102. Nabkasom C, Miyai N, Sootmongkol A, et al. Effects of physical exercise on depression, neuroendocrine stress
hormones, and physiological fitness in adolescent females with depressive symptoms. Eur J Public Health
2006;16:179-184.
103. Cho KJ, Moon HE, Moini H, et al. Alpha-lipoic acid inhibits adipocyte differentiation by regulating pro-
adipogenic transcription factors via mitogen-activated protein kinase pathways. J Biol Chem. 2003 Sep
2;278(37):34823-33.
104. Jacob S, Ruus P, Herman R, et al. Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in
patients with type-2 diabetes mellitus:a placebo-controlled pilot trial. Free Radic Biol Med. 1999 Aug;27
(3-4):309-14
105. Packer L, Kraemer K, Rimbach G. Molecular aspects of lipoic acid in the prevention of diabetes complications.
Nutrition. 2001 Oct;17(10):888-95.
106. Sola S, Mir MQ,Cheeema FA, et al. Irbesartan and lipoic acid improve endothelial function and reduce markers
of inflammation in the metabolic syndrome: results of the Irbesartan and Lipoic Acid in Endothelial
Dysfunction (ISLAND) study. Circulation.2005 Jan 25;111(3):343-8.
107. Savage DB, Petersen KF, Shulman GI. Mechanisms of insulin resistance in humans and possible links with
inflammation. Hypertension.2005 May; 5(5):828 -33.
108. Perseghin G, Petersen K, Shulman GI. Cellular mechanism of insulin resistance:potential links with
inflammation. Int J Obes Relat Metab Disord. 2003 Dec;27 Suppl 3S6-11.
109. Azzi A, Gysin R, Kempna P, et al. Regulation of gene expression by alpha-tocopherol. Biol Chem. 2004
Jul;385(7):585-91.
110. Fattoritti P, Bertoni-Freddari C, Casoli T, et al. Decreased expression of glucose transport protein (Glut3) in
aging and vitamin E deficiency. Ann NY Acad Sci.2002 Nov;973:293-6.
111. Ford ES, Mokdad AH, Giles WH, Brown DW. The metabolic syndrome and antioxidant concentrations:
findings from the Third National Health and Nutrition Examination Survey. Diabetes. 2003 Sep;52(9):2346-
52.
112. Khan A, Safdar M, Ali Khan MM, Khattak KN, Anderson RA, Cinnamon improves glucose and lipids of
people with type 2 diabetes. Diabetes Care.2003Dec;26(12):3215-8.
113. Mancini-Filho J, Van Koiij A, Mancini DA, Cozzolino FF, Torres RP. Antioxidant activity of
cinnamon (Cinnamon Zeylanicum, Breyne) [Link] Chim Farm.1998 Dec;137(11):443-7.
114. Anderson RA, Broadhurst CL, Polansky MM, et al. Isolation and characterization of polyphenol type-A
polymers from cinnamon with insulin-like biological activity. J Agric Food Chem. 2004 Jan 14;52(1):65-70.
115. Imparl-Radosevich J, Deas S, Polansky MM, et al. Regulation of PTP-1 and insulin receptor kinase by fractions
from cinnamon: implications for cinnamon regulation of insulin singnalling. Horm Res. 1998 Sep;50(3):177-82.
116. Jarvil-Taylor KJ, Anderson RA, Graves DJ. A hydroxychalcone derived from cinnamon functions as a
mimetic for insulin in 3T3-L1 adipocytes. J Am Coll Nutr.2001 Aug;20(4):327-36.
117. McCarty MF. A chlorogenic acid-induced increase in GLP-1 production may mediate the impact of heavy coffee
consumption on diabetes risk. Med Hypotheses.2005;64(4):848-53.
118. Ha CH, So WY. Effects of combined exercise training on body composition and metabolic syndrome factors.
Iran J Public Health 2012;41:20-26.
119. Malin SK, Niemi N, Solomon TP, et al. Exercise training with weight loss and either a high- or low-glycemic
index diet reduces metabolic syndrome severity in older adults. Ann Nutr Metab 2012;61:135-141.
120. Solomon TP, Haus JM, Kelly KR, et al. A low-glycemic index diet combined with exercise reduces insulin
resistance, postprandial hyperinsulinemia, and glucose-dependent insulinotropic polypeptide responses in
obese, prediabetic humans. Am J Clin Nutr 2010;92:1359-1368.
121. Smith JA, Greer T, Sheets T, Watson S. Is there more to yoga than exercise? Altern Ther Health
Med 2011;17:22-29.
122. Streeter CC, Whitfield TH, Owen L, et al. Effects of yoga versus walking on mood, anxiety, and brain GABA
levels: a randomized controlled MRS study. J Altern Complement Med 2010;16:1145-1152.
123. Nabkasom C, Miyai N, Sootmongkol A, et al. Effects of physical exercise on depression, neuroendocrine stress
hormones, and physiological fitness in adolescent females with depressive symptoms. Eur J Public Health
2006;16:179-184.
Serving size : 1 Servings per pack :100
Tablet
Each film coated tablet contains
Eugenia Jambolana extract 100mg
Curcuminoids 50mg Epigallocatechin gallate (EGCG) 10mg
Berberine Hydrochloride 50mg from Greeen tea extract
Mulberry leaf extract 4:1 Cynarins 33.5mg Alpha lipoic acid 100mg
from Artichoke leaf extract 5mg Chromium (as Chromium picolinate) 40mcg
Banaba leaf extract Selenium (as L-Selenomethionine) 55mcg
L-Glutathione 12mg Magnesium 40mg
Gymnemic acids 2.5mg Vitamin C 40mg
from Gymnema sylvestre extract 10mg Vitamin D3 10mcg
Charantin Methylcobalamine 500mcg
from Bitter melon exract 10mg Vitamin E 12mg
Methyl hydroxy chalcone polymers Vitamin K 30mcg
from Cinnamon extract 6.25mg Vanadium 1mg
4-Hydroxy isoleucine Biotin 50mcg
from Fenugreek 1.25mg Benfotiamine 25mg
Anthocyanins
from Bilberry fruit extract Isoleucine 25mg
3.10mg
Glycine 25mg
N-acetyl cysteine 25mg

Hyderabad, Telangana, INDIA

[Link]