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Use of Dietary Supplements for Blood Sugar Regulation

Prevalence of Pre-diabetes and Type 2 Diabetes

Approximately 17 million Americans have type 2 diabetes, or 5.6% of the population, according to the US Dept. of
Health & Human Services. Another 16 million are estimated to be pre-diabetic with impaired glucose tolerance.
One of every 3 to 4 individuals (70 million), is likely to be insulin resistant and have increased risk to develop pre-
diabetes, Syndrome X, or type 2 diabetes. Genetic predisposition is likely to be 50 percent responsible for insulin
resistance, and lifestyle habits are likely to account for the other half.
Definition and Diagnosis of Pre-diabetes
The American Diabetes Association (ADA) has formally defined pre-diabetes as having either impaired fasting
glucose (IFG) concentration between 110 and 126 mg/dL, or, impaired glucose tolerance (IGT) with a fasting
glucose less than 126 mg/dL and plasma glucose concentration between 140 and 200 mg/dL 120 minutes after
intake of 75 grams of oral glucose. The utility of the diagnosis of pre-diabetes is to initiate weight loss programs in
overweight individuals, encourage increased physical activity in sedentary individuals, and to identify and treat the
other coronary heart disease risk factors of dyslipidemia and hypertension which are increased in prevalence in these
individuals. Each year, approximately 5% of all individuals within the pre-diabetic group progress into developing
type 2 diabetes. The vast majority of pre-diabetic individuals, even if they don’t develop type 2 diabetes, have
manifestations of Syndrome X and increased risk of heart attack. According to a recent survey of physicians
commissioned and reported by the ADA, “…of the more than 17 million people living with diabetes, 65 percent will
die from a heart attack or stroke.”
Lifestyle Modifications

Many scientists believe that calorie restriction, a healthy diet and weight loss combined with increased physical
activity would be an effective means—possibly even more effective than drugs like metformin—to reduce the
incidence of diabetes in those that are pre-diabetic, and there is definitive evidence to support that idea.
Studies show that dietary changes alone can somewhat reduce risk of type 2 diabetes. Some studies have also
shown that moderate alcohol intake among those who drink alcohol may decrease risk. Smoking worsens pre-
diabetes, Syndrome X, and type 2 diabetes, as can certain prescription drugs for hypertension, which increase LDL
cholesterol and triglyceride levels while lowering HDL cholesterol.

Use of Individual Supplements
Chromium

Description. Chromium is essential for normal binding of insulin to cell receptors and receptor activity. When
insulin receptors are activated, a complex signaling system and set of reactions begin that result in the transport of
glucose from plasma into cells.
Actions and Pharmacology. Chromium’s mechanism of action is not fully understood. However, chromium may
activate insulin receptor kinase activity and inhibit insulin receptor tyrosine phosphatase, leading to increased
phosphorylation of the receptor and increased insulin sensitivity. Clinical studies have suggested that chromium
improves glucose tolerance. Chromium may also have anti-atherogenic effects through glucose regulatory
mechanisms.
Usage and Dosage. From 200-1000 mcg daily. Chromium has been used safely in amounts up to 1000 mcg daily.
Research Summary. Since the mid-1960’s, more than 30 studies have reported beneficial effects of supplemental
chromium in people ingesting normal diets. However, not all studies conducted showed benefit. The response to
chromium supplementation for glucose, insulin, and lipids is related to the amount and form of supplementation,
duration, and degree of glucose tolerance in subjects. Recent studies using chromium supplementation ranging from
200-1000 mcg report improved glucose and insulin parameters in type 2 diabetics, and improved insulin sensitivity
in healthy obese subjects with a family history of type 2 diabetes and overweight, exercising young women.
Contraindications, Precautions, Adverse Reactions. Generally, chromium supplementation is well tolerated.
Pregnant women and nursing mothers should limit their intake to the recommended safe dose of 50-200 mcg per
day, unless monitored by their physician. Those with type 2 diabetes mellitus should consult their physician so that
their blood glucose levels can be appropriately monitored and medications adjusted, should their insulin resistance
decrease.
Interactions: Drugs.
Beta-blockers taken in conjunction with chromium may increase HDL-cholesterol levels.
Vanadium
Description. Vanadium is a trace mineral that may be life-essential.
Actions and Pharmacology. Research suggests that vanadium is essential to normal insulin function. Evidence is
accumulating, showing that vanadium mimics insulin action in isolated cell systems.
Usage and Dosage. Range of 10 mcg to 1800 mcg. is considered safe. However, clinical studies with vanadium
compounds have shown benefits in increasing insulin sensitivity in type 2 diabetics at a dosage of 100 milligrams
vanadyl sulfate (31 mg elemental vanadium) daily for up to 4 weeks.
Research Summary. Studies demonstrate that vanadium significantly mimics insulin action and lowers plasma
glucose at pharmacological doses in animals and humans with diabetes.
Contraindications, Precautions, Adverse Reactions, Interactions. No known contraindications at physiologic
doses. Adverse reactions of diarrhea, green tongues, nausea, vomiting, and cramps are reported at dosage levels 4.5
to 22.5 mg per day. Ferrous ion, chloride, EDTA, chromium, and aluminum hydroxide may impair absorption of
vanadium.
Magnesium
Description. Magnesium is an essential mineral affecting more than 300 metabolic functions and every biological
process.
Actions and Pharmacology. Magnesium may have profound glucose-regulatory activity. The mechanism is
unclear, but may affect insulin receptor binding or signal transduction.
Usage and Dosage. Studies show an inverse relationship between amounts of magnesium ingested and uptake, with
lower amounts showing more efficacious absorption. Doses varied between 7 to 1,000 mg.
Research Summary. Supplemental magnesium has been shown to improve insulin response and glucose handling
in the elderly and in type 2 diabetics. Several large scale, prospective studies have associated low serum magnesium
with greater risk of developing type 2 diabetes, or have found that non-diabetics consuming the highest amount of
magnesium can lower their risk of developing type 2 diabetes by about one-third, compared to those consuming the
least magnesium.
Contraindications, Precautions, Adverse Reactions, Interactions. Ensure adequate levels. Contraindicated in
people with heart block or renal failure. Amounts over 350 mg. may cause loose stool in some sensitive individuals.
Alpha-Lipoic Acid
Description. Alpha-lipoic acid is a compound involved in energy production, and is a powerful antioxidant.
Actions and Pharmacology. Alpha-lipoic acid is synthesized in the body, where it acts as an antioxidant with free
radical scavenging activity, and is involved in the regeneration of antioxidants such as vitamins C, E, and
glutathione. It may stimulate glucose transport.
Usage and Dosage. For treating diabetic neuropathy: 600-1200 mg daily. In Europe it is available for diabetic
neuropathy in 300 mg doses, divided into 150 mg doses twice daily.
Research Summary. Experimental studies in cell culture and animal models of diabetes suggest that alpha-lipoic
acid may stimulate glucose transport. Safety of large oral and intravenous doses has been demonstrated in clinical
trials showing benefit in subjects with diabetic neuropathy. In studies of type 2 diabetics, large oral doses have been
shown to improve insulin resistance or glucose effectiveness after 4 weeks of treatment.
Contraindications, Precautions, Adverse Reactions, Interactions. Pregnant women or nursing mothers should
avoid alpha-lipoic acid supplements at pharmacologic doses. In general, it is well tolerated.
Taurine
Description. Taurine is a non-protein amino acid manufactured in the body. Dietary intake averages 40-300 mg
daily.
Actions and Pharmacology. Taurine plays a role in detoxification, platelet function, central nervous system
development, and acts as a membrane stabilizing antioxidant.
Usage and Dosage. Normal dosages range from 500 to 1000 mg.
Research Summary. Experiments have shown taurine to improve insulin sensitivity in animal models of insulin
resistance and spontaneous type 2 diabetes. Some researchers have proposed that taurine supports glucose transport
by its effects on membranes. Decreased nerve conduction velocity in diabetics is correlated with taurine depletion,
and studies have shown that taurine supplementation prevents diabetic neuropathy and counters oxidative stress in
animal models.
Contraindications, Precautions, Adverse Reactions, Interactions. No adverse reactions. Pregnant women and
nursing mothers should consult their physicians before taking taurine.
Zinc
Description. Zinc is a mineral that plays a clear role in normal production, storage and secretion of insulin. It is
necessary for the conformational integrity of insulin.
Actions and Pharmacology. Zinc is vital for numerous immune and metabolic functions, but it’s role and influence
is not fully understood. It is known to have antioxidant activity.
Usage and Dosage. Deficiencies in zinc can lead to adverse health effects. Typical supplemental dose: 15 mg daily.
Research Summary. Studies have found that increased urinary loss of zinc is common in diabetes. Evidence also
suggests that elevated glucose may induce higher intracellular levels of zinc-requiring antioxidant enzymes, and that
zinc and chromium supplementation can significantly reduce biomarkers of oxidative stress in type 2 diabetics
Contraindications, Precautions, Adverse Reactions, Interactions. Doses up to 30 mg daily are well tolerated.
Significantly higher doses may cause nausea, vomiting, headache, and sleepiness. A typical doses for pregnant
women and nursing mothers is 15 mg daily.
Banaba/Colosolic Acid
Description. Colosolic acid is a triterpene compound derived from the Lagerstroemia speciosa plant, also known as
banaba, from Southeast Asia. Used as a remedy for obesity and diabetes.
Actions and Pharmacology. Banaba extract has been reported to stimulate glucose transport, although how it exerts
this action within the cellular insulin-signaling cascade is not known.
Usage and Dosage. Banaba may decrease blood glucose in type 2 diabetics. Studies have not established a
recommended dosage. Take only with meals.
Research Summary. Most evidence of banaba’s efficacy comes from safe, historical use by indigenous populations
in Asia. Experimental studies have shown that colosolic acid and other components of banaba extract stimulate
glucose transport activity in cultured cells. Other small placebo controlled studies have shown modest hypoglycemic
effects in type 2 diabetics, and improved glucose and insulin response.
Contraindications, Precautions, Adverse Reactions, Interactions. No adverse reactions reported. Due to potential
additive effects when taken in combination with insulin or drugs to manage type 2 diabetes, blood glucose levels
should be monitored. Fasting or reactive hypoglycemics, type 1 diabetics, children, pregnant women and nursing
mothers should not take banaba.
References
1. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. New Engl J Med ;346(6):393-403, 2002. 2. van Dam RM, Rimm EB, Willett WC, Stampfer MJ, Hu FB. Dietary patterns and risk for type 2 diabetes mellitus in U.S. men. Ann Intern 3. Hu FB et al. Diet, lifestyle and the risk of type 2 diabetes mellitus in women. New Eng J of Med 345:790-7, 2001. 4. Reaven GM. The role of insulin resistance in human disease. Diabetes 37:1495-607, 1988 5. Reaven GM, Strom TK, Fox B, Syndrome X The Silent Killer, Simon & Schuster, 2000 6. ADA position statement. Evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications. Diabetes Care 25:S50-60, 2002 7. Vincent JB. Quest for the molecular mechanism of chromium action and its relationship to diabetes. Nutr Rev 58:67-72, 2000 8. Rimm EB et al. Toenail chromium levels and risk of coronary heart disease among normal and overweight men. American Heart Association, 42nd Annual Conference on Cardiovascular Disease, Epidemiology and Prevention, April, 2002. 9. Anderson RA. Review: Chromium, glucose intolerance and diabetes. J Am Coll Nutr 17:548-55, 1998 10. Anderson RA. Review: Chromium in the prevention and control of diabetes. Diab & Metab 26:22-27, 2000 11. Ravina A et al. Clinical use of the trace element chromium (III) in the treatment of diabetes mellitus. J Trace Elem Exp Med 8:183-90, 1995. 12. Anderson RA et al. Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes. 13. Ravina A et al. Control of steroid-induced diabetes with supplemental chromium. J Trace Elem Exp Med 12:375-8, 1999. 14. Jovanovic L. Chromium supplementation for women with gestational diabetes. J Trace Elem Exp Med 12:91-8, 1999. 15. Cefalu WT et al. Effect of chromium picolinate on insulin sensitivity in vivo. J Trace Elem Exp Med 12:71-84, 1999. 16. Grant KE et al. Chromium and exercise training: effect on obese women. Med Sci Sports Exerc 29:992-8, 1997. 17. Balon TW et al. Magnesium supplementation reduces development of diabetes a rat model of spontaneous NIDDM. Am J Physiol 269:E745- 18. Paolisso G et al. Daily magnesium supplements improve glucose handling in elderly subjects. Am J Clin Nutr 55:1161-7, 1992 19. Paolisso G et al. Changes in glucose turnover parameters and improvement of glucose oxidation after 4-week magnesium administration in elderly non-insulin dependent diabetic patients. J Clin Endocrin Metab 78:1510-14, 1994. 20. Nadler JL et al. Intracellular free magnesium deficiency plays a key role in increased platelet reactivity in type II, Diabetes Care 15:835-41, 21. Kao WH et al, Serum and dietary magnesium and risk for type 2 diabetes mellitus: the Atherosclerosis Risk in Communities Study. Arch 22. Meyer KA Carbohydrates, dietary fiber, and incident type 2 diabetes in older women. Am J Clin Nutr 71:921-30, 2000 23. Colditz GA et al. Diet and risk of clinical diabetes in women. Am J Clin Nutr, 55:1018-23, 1992. 24. Chausmer A. Review: Zinc, insulin and diabetes. J Am Coll Nutr. 17:109-115, 1998. 25. Ceriello A et al. High glucose induces antioxidant enzymes in human endothelial cells in culture. Diabetes 46:471-7, 1996 26. Anderson RA et al. Potential antioxidant effects of zinc and chromium supplementation in type 2 diabetes mellitus. J Am Coll Nutr, 20:212- 27. Verma S et al. Review. Nutritional factors that can favorably influence the glucose/insulin system : Vanadium. J Am Coll Nutr 17:11-18, 28. Cohen N et al. Oral vandyl sulfate improves hepatic and peripheral insulin sensitivity in patients with non-insulin dependent diabetes mellitus 29. Boden G et al. Effects of vandyl sulfate on carbohydrate and lipid metabolism in patients with non-insulin-dependent diabetes mellitus. 30. Halberstam M et al.Vanadyl sulfate improves insulin sensitivity in NIDDM but not in obese non-diabetic subjects. Diabetes 45:659-66, 1996 31. Quisumbing E. Medicinal plants of the Philippines. Technical Bulletin 16; Dept. of Agriculture and Natural Resources, 1951. 32. Kakuda T et al. Hypoglycemic effect of extracts from Lagerstroemia speciosa leaves in genetically diabetic KK-A mice. Biosci Biotech 33. Murakami C et al. Screening of plant constituents for effect on glucose transport activity in erlich ascites tumor cells. Chem Pharm Bull 34. Liu F et al. An extract of Lagerstroemia speciosa has insulin like glucose uptake stimulatory and adipocyte differentiation-inhibitory activities in 3T3-L1 cells. J of Nutr 131:2242-7, 2001 35. Hiyashi T et al. Ellagitannins from Lagerstroemia speciosa as activators of glucose transport in fat cells. Planta Med 68:173-5, 2002. 36. Ikeda Y et al. Effectiveness and safety of Banabamin tablets containing an extract from banaba in patients with mild type 2 diabetes. Jpn 37. Ikeda Y et al. Effectiveness and safety in administering banaba extract to those concerned about blood sugar. J of Practical Diabetes 18 (4) 38. Anuradha CV et al. Taurine attenuates hypertension and improves insulin sensitivity in the fructose fed rat, and animal model of insulin resistance. Can J Physiol Pharm 77:749-54, 1999. 39. Nakaya Y et al. Taurine improves insulin sensitivity in the Otsuka Long-Evans fatty rat, a model of spontaneous type 2 diabetes. Am J Clin 40. Kulakowski EC et al. Hypoglycemic properties of taurine: not mediated by enhanced insulin release. Biochem Pharm 33:2835-8, 1994 41. Elizarova EP et al. First (human) experiments in taurine administration for diabetes mellitus: effects on erythrocyte membranes. Adv in Exp 42. Hayes KC et al. Taurine modulates platelet aggregation in cats and humans. Am J Clin Nutr 49:1211-6, 1989 43. Pop-Busui R et al. Depletion of taurine in experimental diabetic neuropathy; implications for nerve metabolic, vascular and functional 44. Obrosova IG et al. Taurine counteracts oxidative stress and nerve growth factor deficit in early experimental diabetic neuropathy. Exp Neurol 45. Packer et al. Review: alpha lipoic acid as a biological antioxidant. Free Rad Biol Med 19:227-50, 1995 46. Marangon K et al. Comparison of the effect of alpha-lipoic acid and alpha-tocopherol supplementation on measures of oxidative stress Free 47. Xu DP et al. Alpha lipoic acid dependent regeneration of ascorbic acid from dehydroascrobic acid in rat liver mitrochondria. J Bioenerg & 48. Yaworsky K et al. Engagement of the insulin-sensitive pathway in the stimulation of glucose transport by alpha-lipoic acid in 3T3-L1 adipocytes. Diabetologia 43:294-303, 2000 49. Estrada DE et al. Stimulation of glucose uptake by the natural coenzyme alpha lipoic acid. Diabetes 45:1798-804, 1996. 50. Zeigler D et al. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid : A 7 month multicenter randomized controlled trial. Diabetes Care 22:1296-1301, 1999. 51. Ziegler D et al. Treatment of symptomatic diabetic peripheral neuropathy with the antioxidant alpha-lipoic acid (ALADIN Study). 52. Jacob S, Ruus P, Hermann 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 Rad Biol Med 27:309-14, 1999 53. Konrad T et al. Alpha-lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with type 2 diabetes. Diabetes Care 22:280-7, 1999. 54. American Diabetes Association, Diabetes Creates Serious Cardiovascular Risk, In The News, 2002-06-17.

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