Living with Diabetes

Living with Diabetes: Supplements to Make the Job Easier

There are two primary types of diabetes: type 1 and type 2. Both types result in high levels of blood sugar levels, which may manifest itself through any of the following symptoms: increased thirst and an increased need to urinate; feeling edgy, tired, and sick to your stomach; and having an increased appetite (but loss of weight). In addition, other symptoms may include: repeated or hard-to-heal infections of the skin, gums, vagina, or bladder; blurred vision; tingling or loss of feeling in the hands or feet; and dry, itchy skin. If left uncontrolled, high blood sugar may result in a variety of serious complications. There are nutrients and supplements that can ease some of the burden of living with diabetes.

Glycosylated protein

Many of these complications are the result of glycosylated protein (GP). GP simply means that sugar (glucose) has attached itself to protein. For example, blood sugar can attach itself to the protein in your red blood cells’ hemoglobin and form glycosylated hemoglobin (HbA1c). Virtually all proteins are glycosylated to some degree. However, if this process continues to excess, eventually you end up with compounds called Advanced Glycosylation End Products (AGE). These AGE become permanent fixtures in our cells. AGE impregnated cells are very reactive and react with one another, and other proteins. In the case of blood capillaries, they can result in the walls of the capillaries thickening, eventually causing the vessels to be blocked off. This is the underlying cause of kidney complications (nephropathy) and eye complications (retinopathy). Unfortunately, the more blood sugar, the more glycosylated proteins.

Sorbitol

Another mechanism by which complications in diabetes result is excessive cellular sorbitol (a type of sugar-alcohol). Many cells in the body do not rely on insulin for glucose uptake. When you have hyperglycemia, you actually get high sugar levels inside these cells, which causes sorbitol to be produced in high concentrations. Intracellular sorbitol disrupts the pressure balance between the inside and outside of the cell, causing water to enter. This swelling of nerve cells is what is believed to be, at least in part, responsible for the nerve damage (neuropathy) caused by diabetes. (This does not mean that if you consume sorbitol in foods that it will have the same effect—it won’t). 

Type 1 Diabetes

Type 2 Diabetes

Type 2 diabetes used to be called non-insulindependent diabetes. The most common type of diabetes, it affects about 15 million Americans. Nine out of ten cases of diabetes are type 2. It usually occurs in people over 45 and overweight, among other factors. When you have type 2 diabetes, your body does not make enough insulin—or your body still makes insulin but can't properly use it. Without enough insulin, your body cannot move blood sugar into the cells. Sugar builds up in the bloodstream. Conventional medical treatment for type 2 diabetes includes any of the following, alone or in combination: insulin injections, oral drugs, or diet alone.

Following is a discussion about dietary supplements that may help diabetics to gain greater control over their blood sugar levels, reduce the long-term detrimental effects of high blood sugar levels, or both. 

Chromium

Chromium levels can be below normal in patients with diabetes.^{1 2} In a randomized, placebo-controlled study³ , 180 men and women with type 2 diabetes were divided into three groups and supplemented with: 1) placebo, 2) 200 mcg chromium daily, or 3) 1,000 mcg chromium daily (from chromium picolinate for both doses).Subjects continued to take their normal medications and were instructed not to change their normal eating and living habits. The results were that that both doses of supplemental chromium had significant beneficial effects on HbA1c, glucose, insulin, and cholesterol variables, although the benefits were greater with the higher dose.

Other studies show that taking chromium picolinate orally can decrease fasting blood glucose, decrease HbA1c levels, decrease triglyceride levels, and increase insulin sensitivity in people with type 2 diabetes. ^{4 5} Some evidence also suggests that chromium picolinate might decrease weight gain and fat accumulation in type 2 diabetes patients who are taking a sulfonylurea.⁶ Higher chromium doses (1,000 mcg) might be more effective and work more quickly.⁷ Higher doses might also reduce triglyceride and total serum cholesterol levels in some patients. ^{8 9} Additional research demonstrated that chromium picolinate may have the same benefits in patients with type 1 diabetes¹⁰ and in patients who have diabetes secondary to corticosteroid use.¹¹

Banaba

Banaba is the common name for Lagerstroemia speciosa, a traditional herbal medicine used among diabetics in the Philippines.¹² Research done on Banaba extract has demonstrated that it has an “insulin-like principle” as well as an ability to reduce blood sugar. At least one component of this insulinlike principle is thought to be corosolic acid, although Banaba also contains other like candidates including ellagitannins, lagerstroemin, flosin B, reginin A. As a matter of fact, a recent study identified ellagitannins from Banaba as activators of glucose transport.¹³

One of the Banaba studies was conducted hereditary diabetic mice. The results showed blood sugar increases were suppressed, and the level of serum insulin and the amount of urinary excreted glucose were also lowered in mice fed Banaba extract. The researchers suggested Banaba extract has beneficial effects on control of blood levels of glucose in noninsulin dependent diabetes mellitus.¹⁴

Twelve diabetic subjects taking 48 mg of the Banaba extract were tested in a randomized, double-blind crossover study. This study confirmed that a Banaba extract promotes normal blood glucose metabolism in people with type 2 diabetes, and also showed that Banaba extract’s benefits were sustained for several weeks even after discontinuation of the supplement.¹⁵

Another crossover, placebo-controlled clinical study with 24 subjects found similar results. Specifically, Banaba extract was effective in reducing blood glucose levels even in short-term (4 weeks) treatment, with no signs of adverse effects. Furthermore, even a one-time dose leaves a memoryeffect for blood glucose control. Compared to the placebo group, a statistically significant drop in the average blood glucose level is observed with the administration of Banaba extract ¹⁶

Gymnema sylvestre

Animal studies have demonstrated that the herb Gymnema sylvestre is capable of lowering blood glucose levels, improving glucose utilization, and increasing insulin levels in diabetes.^{17 18 19 20} The latter benefit was found to be a function of Gymnema’s apparent ability to repair/regenerate beta cells, the parts of the pancreas responsible for producing insulin.²¹

Of greater significance to diabetic patients is the research conducted on humans. In one study, 22 type 2 diabetic patients received Gymnema for 18-20 months, as a supplement to the conventional oral drugs. During Gymnema supplementation, the patients showed a significant reduction in blood glucose, glycosylated hemoglobin and glycosylated blood proteins; and conventional drug dosage could be decreased. As a matter of fact, five of the 22 diabetic patients were able to discontinue their conventional drug and maintain their blood glucose homeostasis with Gymnema alone. The researchers concluded that “These data suggest that the beta cells may be regenerated/repaired in type 2 diabetic patients on [Gymnema] supplementation. This is supported by the appearance of raised insulin levels in the serum of patients after [Gymnema] supplementation.”²²

In a similar study, Gymnema was administered to 27 patients with type 1 diabetes, who were also on insulin therapy. The results were that insulin requirements came down together with blood glucose and glycosylated hemoglobin and glycosylated blood protein levels. Blood fats also returned to near normal levels with Gymnema therapy. Type 1 diabetic patients who were just on insulin therapy (no Gymnema), showed no significant reduction in serum lipids, glycosylated hemoglobin or glycosylated blood protein when followed up after 10-12 months. The researchers of this study concluded, “Gymnema therapy appears to enhance endogenous insulin, possibly by regeneration/revitalization of the residual beta cells in insulin-dependent diabetes mellitus.²³

Bitter Melon

Bitter melon (Momordica charantia) is a tropical vegetable widely cultivated in Asia, Africa and South America, and has been used extensively in traditional folk medicine as a remedy for diabetes. This traditional use has also been validated by clinical research. In one study, Bitter melon was found to significantly improve the glucose tolerance of 73% of patients with adult-onset diabetes (type 2).²⁴ During another study, Bitter Melon significantly reduced blood glucose concentrations during a glucose tolerance test in type 2 diabetics.²⁵ Other research has identified the protein component of Bitter Melon that have the blood sugar lowering effects, and those researchers have stated that it is very effective for that purpose when administered to “gerbils, langurs, and humans.”²⁶

Alpha Lipoic Acid

A significant amount of research has been conducted on the natural antioxidant Alpha Lipoic Acid (ALA) in the treatment of diabetes. In one study, seventyfour patients with type-2 diabetes were given either a placebo, or ALA.. When compared to the placebo group, those receiving the ALA had significantly greater insulin-sensitivity, and improvement in insulin-stimulated glucose disposal. The researchers logically concluded, “The results suggest that oral administration of alpha-lipoic acid can improve insulin sensitivity in patients with type-2 diabetes.”²⁷ Another benefit of ALA use in diabetics has to do with diabetic neuropathy. In one study on type 2 diabetics, ALA treatment was associated with “a favorable effect on neuropathic deficits without causing significant adverse reactions.”²⁸ In another two-year study, ALA “appeared to have a beneficial effect on several attributes of nerve conduction” in a group of type 2 diabetic patients.²⁹ Additional research on diabetics has shown that ALA has been able to improve other aspects of diabetic neuropathy,^{30 31} including improvements in neuropathy symptoms.^{32 33 34}

Another important consideration is that oxidative stress caused by free radicals can exacerbate the diabetic condition. Research provides evidence that, in type 2 diabetics, treatment with ALA significantly improves antioxidant defense³⁵—even in patients with poor blood sugar control and albuminuria (i.e., too many serum proteins in the urine).³⁶

Finally, one of the most important benefits offered to diabetics by ALA is the fact that it has been shown to enhance the disposal of blood sugar in patients with type 2 diabetes, which gives it great potential as a blood sugar lowering agent.³⁷ In a related study of lean and obese diabetic patients treated with ALA, the ALA prevented increases in metabolites that are typically associated with high blood sugar, and also increased blood sugar effectiveness.³⁸

American ginseng

Panax quinquefolius, more commonly known as American ginseng, was shown to lower the rise in blood sugar following the consumption of a drink high in glucose by people with type 2 diabetes in a small pilot study.³⁹ The same effect was found whether the herb was taken either 40 minutes before the drink or at the same time. In a follow-up study, similar blood sugar lowering results were found; even when American ginseng was given up to two hours before or together with the drink.30 The same researchers conducted additional research on nondiabetic subjects, and again found blood sugar lowering effects from American ginseng.⁴⁰

Fenugreek seeds extract

Fenugreek (Trigonella foenum-graecum) has been used as a traditional herbal medicine for treating diabetes. Modern scientific research lends support to this traditional use. As the result of research conducted on diabetic rats and humans, the International Journal of Obesity recognized Fenugreek as having potential benefit for the control of glucose metabolism.⁴¹ Other research in animals^{42 43 44 45 46} as well as humans^{47 48} has also shown that Fenugreek is capable of lowering blood glucose levels in diabetic, as well as non-diabetic subjects.

Some of the studies assumed that it was the soluble fiber content of the Fenugreek seeds that provided the glucose modulating effect. However, other studies found that there were other natural components present which are also involved. ^{49 50} In fact, one study found an enzyme in Fenugreek is implicated in synthesizing an unusual amino acid called 4- hydroxyisoleucine, which is known for its insulin stimulating effect.⁵¹

Co-enzyme Q10

Research has shown that some diabetic patients who use diet to control their blood sugar may have a deficiency of Co-enzyme Q10 (CoQ10), which may be further exacerbated by certain commonly used antidiabetic drugs. Such a deficiency of CoQ10 in the pancreas could impair aspects of energy metabolism, and the biosynthesis of insulin.⁵² Other research has also demonstrated that CoQ10 levels are lower in diabetic patients, which can cause diabetic cardiomyopathy. That same research, however, also showed that the diabetic cardiomyopathy can also be reveresed by CoQ10 supplementation.⁵³ And speaking of a cardiac condition, research has also demonstrated that CoQ10 exhibits an effective antiarrhythmic (i.e., prevents abnormal heart beat) in patients with diabetes.⁵⁴

A newly discovered form of diabetes is referred to as maternally inherited diabetes mellitus and deafness (MIDD). The characteristic clinical features of MIDD are progressive worsening of insulin secretion and, as the name would suggest, neurosensory deafness and maternal inheritance. After three years of treatment with CoQ10 therapy on MIDD patients, progressive hearing loss was prevented and blood sugar metabolites improved after exercise. Furthermore, there were no side effects during therapy.⁵⁵

Bilberry

One clinician/researcher had this to say about Bilberry (a European relative of the American Blueberry): "Perhaps the most significant clinical applications for bilberry extracts are in the field of ophthalmology.” The health of the eye depends on a rich supply of nutrients and oxygen, and, “Relatively speaking, the amount of blood blow through the eye is the greatest in the body.” Bilberry appears to support vision by improving the delivery of oxygen and blood, “as well as exert[ing] other important pharmacological effects,” including acting as an antioxidant. Among other benefits, Bilberry has proven effective in treating or preventing diabetic retinopathy, and macular degeneration. Bilberry’s strengthening effect on collagen may explain its benefit in helping to treat diabetic retinopathy. It also effectively regulates blood sugar levels in diabetic subjects.⁵⁶

Inositol

An altered metabolism of inositol, a natural substance associated with the B complex group of vitamins, has been documented in patients with diabetes.⁵⁷ In fact, over 20 years ago, researchers found that high blood sugar levels in diabetes “may condition a widespread relative intracellular inositol deficiency, and suggest that restoration of normal intracellular inositol concentrations might prove to be of benefit in the prevention and treatment of certain of the complications associated with human diabetes mellitus.”⁵⁸ As it turned out, supplementation with inositol has indeed proven beneficial for diabetics. For example, low levels of inositol have been associated with neuropathy in diabetic patients,⁵⁹ and inositol supplementation has been demonstrated to be effective in treating diabetic neuropathy.⁶⁰ Another benefit is that supplementation with inositol can help prevent the premature aging of certain cells in the diabetic which is caused by elevated concentrations of blood sugar.⁶¹ Other research suggests that inositol may exert a protective effect on slowly developing diabetic cataracts.⁶²

Finally, consider that the incidence of major congenital malformations is approximately 6-9% in pregnancies complicated by diabetes mellitus. This incidence is 3-4-fold higher than that in the general population. Congenital malformations are now ranked as the leading cause of death in the offspring of women with diabetes. This particular type of congenital malformation in the offspring of diabetic women is referred to as diabetic embryopathy.

Dietary supplementation of inositol has been shown to reduce the incidence of diabetes-related malformations in offspring of diabetic pregnant animals.⁶³ Researchers have indicated that supplementation with inositol offers great promise, in addition to blood sugar control, as a dietary preventive measure against diabetic embryopathy.⁶⁴

Antioxidants

Antioxidants block the production of AGE. Hence, any good antioxidant has potential value for use by diabetics. Thus far we’ve examined three antioxidants: Alpha Lipoic Acid, Co-enzyme Q10 and Bilberry. Following is a description of a few others antioxidants which may have value for diabetics.

Gingko biloba extract

In addition to its antioxidant properties, Ginkgo biloba extract enhances peripheral circulation and will highly benefit vascular disease. Ginkgo promotes blood flow in both healthy and compromised blood vessels. Many medical experts actually advise aspirin therapy for diabetics to thin the blood and reduce its stickiness. Ginkgo does this naturally. The benefits of Ginkgo biloba extract are primarily attributed to two groups of active constituents: the ginkgo flavone glycosides and the terpene lactones. Ginkgo flavone glycosides, which typically make up approximately 24% of the extract, are primarily responsible for GBE’s antioxidant activity and mildly inhibit platelet aggregation (stickiness). GBE’s antioxidant action may also extend to the brain and retina of the eye.⁶⁵ Preliminary trials have suggested potential benefit for people with macular degeneration⁶⁶ and diabetic retinopathy.⁶⁷

Turmeric

Turmeric is a bright yellow, ancient spice and a traditional remedy that has been used as a medicine, condiment and flavoring based on records dating back to 600 BCE. Its medicinal value is essentially due to its curcuminoid content. The curcuminoids inhibit 5-lipo-oxygenase (LOX) and cyclo-oxygenase (COX), resulting in a well-established antiinflammatory action.^{68 69 70} Turmeric and its curcuminoids also exhibit strong antioxidant activity⁷¹, enhance cellular resistance to oxidative damage⁷², and enhance the body's natural antioxidant glutathione levels; which in turn aids the liver in detoxification.⁷³

Grape Seed Extract

Grape Seed Extract is a source of oligomeric proanthocyanidins (OPCs). Not only do OPCs have significant antioxidant properties, but they also help stabilize collagen and maintain elastin;^{74 75} important proteins in connective tissue that support organs, joints, blood vessels, and muscle. In double-blind research, OPCs have been shown to strengthen capillaries, ⁷⁶ and improve venous blood flow;⁷⁷ important considerations for diabetics. Furthermore, OPCs have improved visual performance in the dark and after exposure to glare.^{78 79}

Schizandra

Schizandra’s value as an antioxidant is wellestablished.^{80 81} Also, it appears that the lignans in Schizandra activate enzymes in liver cells that produce the antioxidant glutathione.⁸² In addition to its antioxidant properties, Schizandra is also regarded as an adaptogen in Russia.⁸³ Research indicates that Schizandra can improve work performance, build strength, reduce fatigue, and increase endurance^{84 85}; all consistent with the effects of an adaptogen, and all of value to a diabetic.

Green Tea Extract

Green, Oolong and black (‘normal’) tea are all made from the leaves of the same plant species. Green, unfermented tea is the world’s second most popular beverage, after water. It is the polyphenols in Green Tea, specifically the catechin polyphenols, which gives it biological and medicinal qualities. Catechins, particularly one called Epigallocatechin gallate (EGCg), are what give Green Tea its antioxidant, antimicrobial, blood thinning, and cholesterol lowering activities;⁸⁶ all of which should be of interest to diabetics.

A word of caution

If you are diabetic and controlled on medication, make your health professional aware of any changes you intend to make in your lifestyle. Diet, exercise, and supplements may affect your blood sugar levels. Make your doctor a participant in any changes you would like to make in your health management. This will assure that you are being properly monitored and that you will keep yourself out of trouble.

By Gene Bruno, MS, MHS & Art Presser, PharmD. Smart Supplementation™ is a free series of educational literature created by Huntington College of Health Sciences (HCHS) as a public service. Although copyrighted, it may be freely photocopied and distributed, but may not be altered in any way. Smart Supplementation™ is not intended as medical advice. For diagnosis and treatment of any medical condition, consult your physician. 

Reference

1 Davies S, Howard JM, Hunnisett A, et al. Age-related decreases in chromium levels in 51,665 hair, sweat, and serum samples from 40,872 patients – implications for the prevention of cardiovascular disease and type II diabetes. Metabolism 1997;46:469-73. 2 Morris BW, Kemp GJ, Hardisty CA. Plasma chromium and chromium excretion in diabetes. Clin Chem 1985;31:334-5. 3 Anderson RA, Cheng N, Bryden NA, et al. Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes. Diabetes 1997;46:1786-91. 4 Rabinovitz H, Friedensohn A, Leibovitz A, et al. Effect of chromium supplementation on blood glucose and lipid levels in type 2 diabetes mellitus elderly patients. Int J Vitam Nutr Res 2004;74:178-82. 5 Martin J, Wang ZQ, Zhang XH, et al. Chromium picolinate supplementation attenuates body weight gain and increases insulin sensitivity in subjects with type 2 diabetes. Diabetes Care 2006;29:1826-32. 6 Martin J, Wang ZQ, Zhang XH, et al. Chromium picolinate supplementation attenuates body weight gain and increases insulin sensitivity in subjects with type 2 diabetes. Diabetes Care 2006;29:1826-32. 7 Anderson RA, Cheng N, Bryden NA, et al. Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes. Diabetes 1997;46:1786-91. 8 Lee NA, Reasner CA. Beneficial effect of chromium supplementation on serum triglyceride levels in NIDDM. Diabetes Care 1994;17:1449-52. 9 Anderson RA, Cheng N, Bryden NA, et al. Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes. Diabetes 1997;46:1786-91. 10 Fox GN, Sabovic Z. Chromium picolinate supplementation for diabetes mellitus. J Fam Pract 1998;46:83-6. 11 Ravina A, Slezak L, Mirsky N, et al. Reversal of corticosteroidinduced diabetes mellitus with supplemental chromium. Diabet Med 1999;16:164-7. 12 Suzuki Y, Unno T, Ushitani M, et al. Antiobesity activity of extracts from Lagerstroemia speciosa L. leaves on female KK-Ay mice. Journal of nutritional science and vitaminology 1999; 45(6):791-5. 13 Hayashi T, Maruyama H, Kasai R, et al. Ellagitannins from Lagerstroemia speciosa as activators of glucose transport in fat cells. Planta medica 2002; 68(2):173-5. 14 Kakuda T, Sakane I, Takihara T, et al. Hypoglycemic effect of extracts from Lagerstroemia speciosa L. leaves in genetically diabetic KK-AY mice. Bioscience, biotechnology, and biochemistry 1996; 60(2):204-8. 15 Judy, W. V. Glucosol™ Clinical Study Synopsis (1999) Report from Soft Gel Technologies, Inc. 16 Judy, W. V. Glucosol™ Clinical Study Synopsis (1999) Report from Soft Gel Technologies, Inc. 17 Shimizu K, et al, J Vet Med Sci (1997) 59(9):753-7. 18 Okabayashi Y, et al, Diabetes Res Clin Pract (1990) 9 (2):143-8. 19 Shanmugasundaram KR, J Ethnopharmacol (1983) 7(2):205-34. 20 Shanmugasundaram ER, et al, J Ethnopharmacol (1990) 30(3):265-79. 21 Ibid. 22 Baskaran K, et al, J Ethnopharmacol (1990) 30(3):295-300. 23 Shanmugasundaram ER, et al, J Ethnopharmacol (1990) 30(3):281-94. 24 Welihinda J, et al, J Ethnopharmacol (1986) 17(3):277-82. 25 Leatherdale BA, et al, Br Med J (1981) 282(6279):1823-4. 26 Khanna P, et al, J Nat Prod (1981) 44(6):648-55. 27 Jacob S, et al, Free Radic Biol Med (1999) 27(3-4):309-14. 28 Ziegler D, et al, Diabetes Care (1999) 22(8):1296-301. 29 Reljanovic M, et al, Free Radic Res (1999) 31(3):171-9. 30 Haak ES, et al, Microvasc Res (1999) 58(1):28-34. 31 Ziegler D, et al, Diabetes Care (1997) 20(3):369-73. 32 Strokov IA, et al, Zh Nevrol Psikhiatr Im S S Korsakova (1999) 99(6):18-22. 33 Ziegler D, et al, Diabetes (1997) 46 Suppl 2:S62-6. 34 Ziegler D, et al, Diabetologia (1995) 38(12):1425-33. 35 Roy S, et al, Biochem Pharmacol (1997) 53(3):393-9. 36 Borcea V, et al, Free Radic Biol Med (1999) 26(11-12):1495- 500. 37 Jacob S, et al, Arzneimittelforschung (1995) 45(8):872-4. 38 Konrad T, et al, Diabetes Care (1999) 22 (2):280-7. 39 Vuksan V, Sivenpiper JL, Koo VYY, Francis T, BeljanZdravkovic U, Xu Z, Vidgen E. American ginseng (Panax quinquefolius L.) reduces postprandial glycemia in nondiabetic subjects and subjects with type 2 diabetes mellitus. Arch Intern Med 2000; 160:1009–13. 40 Vuksan V, Sievenpiper JL, Wong J, Xu Z, Beljan-Zdravkovic U, Arnason JT, Assinewe V, Stavro MP, Jenkins AL, Leiter LA, Francis T. American ginseng (Panax quinquefolius L.) attenuates postprandial glycemia in a time-dependent but not dose-dependent manner in healthy individuals. Am J Clin Nutr. 2001; 73(4):753-8. 41 Madar Z. New source of dietary fiber [Review]. International Journal of Obesity 1987; Suppl.1:57-65. 42 Ajabnoor MA, Tilmisany AK. Effect of Trigonella foenum graecum on blood glucose levels in normal and alloxandiabetic mice. Journal of Ethnopharmacology 1988; 22:45-49. 43 Al-Habori M, Raman A. Antidiabetic and hypocholesterolemic effects of fenugreek. Phytotherapy Research 1988; 12:233-242. 44 Khosla P, Gupta DD, Nagpal RK. Effect of Trigonella foenum graecum (Fenugreek) on blood glucose in normal and diabetic rats. Indian Journal of Physiology and Pharmacology 1995; 39:173-174. 45 Ali L, Azad Khan AK, Hassan Z, et al. Characterization of the hypoglycemic effects of Trigonella foenum graecum seed. Planta Medica 1995; 61:358-360. 46 Ribes G, Sauvaire Y, Da Costa C, et al. Antidiabetic effects of subfractions from fenugreek seeds in diabetic dogs. Proceedings of the Society for Experimental Biology and Medicine 1986; 182:159-166. 47 Sharma, RD, Raghuram TC, Rao NS. Effect of fenugreek seeds on blood glucose and serum lipids in Type I diabetes. European Journal of Clinical Nutrition 1990; 44:301-306. 48 Madar Z, Abel R, Samish S, Arad J. Glucose-lowering effect of fenugreek in non-insulin dependent diabetics. European Journal of Clinical Nutrition 1988; 42:51-54. 49 Ali L, Azad Khan AK, Hassan Z, et al. Characterization of the hypoglycemic effects of Trigonella foenum graecum seed. Planta Medica 1995; 61:358-360. 50 Ribes G, Sauvaire Y, Da Costa C, et al. Antidiabetic effects of subfractions from fenugreek seeds in diabetic dogs. Proceedings of the Society for Experimental Biology and Medicine 1986; 182:159-166. 51 Haefele C, Bonfils C, Sauvaire Y. Characterization of a dioxygenase from Trigonella foenum graecum involved in 4- hydroxyisoleucine biosynthesis. Phytochemistry 1997; 44:563- 566. 52 Kishi T, et al, J Med (1976) 7(3-4):307-21. 53 Miyake Y, et al, Arzneimittelforschung (1999) 49(4):324-9. 54 Fujioka T, Sakamoto Y, Mimura G, Tohoku J Exp Med (1983) 141 Suppl:453-63. 55 Suzuki S, Diabetologia (1998) 41(5):584-8. 56 Murray M, American Journal of Natural Medicine (1997) 4(1):18-22. 57 Holub BJ, Adv Nutr Res (1982) 4:107-41. 58 Clements RS Jr, Reynertson R, Diabetes (1977) 26(3):215-21. 59 Servo C, Bergstrom L, Fogelholm R, Acta Med Scand (1977) 202(4):301-4. 60 Pfeifer MA, Schumer MP, Diabetes (1995) 44(12):1355-61. 61 Sibbitt WL Jr, et al, Mech Ageing Dev (1989) 47(3):265-79. 62 Beyer-Mears A, et al, Pharmacology (1989) 39(1):59-68. 63 Reece EA, et al, J Soc Gynecol Investig (1998) 5(4):178-87. 64 Reece EA, Homko CJ, Wu YK, Teratology (1996) 54(4):171-82. 65 Ferrandini C, Droy-Lefaix MT, Christen Y, eds. Ginkgo biloba Extract (EGb 761) as a Free Radical Scavenger. Paris: Elsevier, 1993. 66 Lebuisson DA, Leroy L, Rigal G. Treatment of senile macular degeneration with Ginkgo biloba extract. A preliminary doubleblind, drug versus placebo study. Presse Med 1986;15:1556–8 67 Lanthony P, Cosson JP. Evolution of color vision in diabetic retinopathy treated by extract of Ginkgo biloba. J Fr Ophthalmol 1988;11:671–4 68 Chandra D, Gupta S. Anti-inflammatory and anti-arthritic activity of volatile oil of Curcuma longa (Haldi). Ind J Med Res 1972; 60:138-142. 69 Arora R, Basu N, Kapoor V, et al. Anti-inflammatory studies on Curcuma longa (turmeric). Ind J Med Res 1971;59:1289-1295. 70 Mukhopadhyay A, Basu N, Ghatak N, et al. Anti-inflammatory and irritant activities of curcumin analogues in rats. Agents Actions 1982; 12:508-515. 71 Toda S, Miyase T, Arich H, et al. Natural antioxidants. Antioxidative compounds isolated from rhizome of Curcuma longa L. Chem Pharmacol Bull 1985;33:1725-1728. 72 Mortellini R, Foresti R, Bassi R, Green CJ. Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase- 1 and protects endothelial cells against oxidative stress. Free Radic Biol Med 2000;28:1303-1312. 73 Pizorrno JE, Murray MT. Textbook of Natural Medicine, 2nd Ed. London: Churchill Livingstone; 1999; 689-693. 74 Mitcheva M, Astroug H, Drenska D, et al. Biochemical and morphological studies on the effects of anthocyans and vitamin E on carbon tetrachloride induced liver injury. Cell Mol Bio 1993;3 9:443–8. 75 Maffei F, Carini M, Aldini G, et al. Free radical scavenging action and anti-enzyme activities of procyanidines from Vitis vinifera. A mechanism for their capillary protective action. Arzneimittelforschung 1994; 44:592–601. 76 Dartenuc JY, Marache P, Choussat H. Resistance Capillaire en Geriatrie Etude d’un Microangioprotecteur. Bordeaux Médical 1980;13:903–7 77 Delacroix P. Etude en Double Avengle de l’Endotelon dans l’Insuffisance Veineuse Chronique. Therapeutique, la Revue de Medicine 1981;27–28 Sept:1793–802 78 Corbe C, Boissin JP, Siou A. Light vision and chorioretinal circulation. Study of the effect of procyanidalic oligomers. J Fr Ophtalmol 1988;11:453–60. 79 Boissin JP, Corbe C, Siou A. Chorioretinal circulation and dazzling; use of procyanidolic oligomers. Bull Soc Ophtalmol Fr 1988;88:173–4, 177–9. 80 Kuhn MA, Winston D. Herbal Therapy & Supplements: A Scientific & Traditional Approach. Philadelphia:Lippincott; 2000. 81 Upton R (ed). Schizandra: analytical, quality control and therapeutic monograph. American Herbal Pharmacopoeia 1999;1:1-25. 82 Ip SP, Poon MKT, Wu SS, et al. Effect of schisandrin B on hepatic glutathione antioxidant system in mice: Protection against carbon tetrachloride toxicity. Planta Med 1995; 61:398-401. 83 Bone K. Clinical Applications of Ayurvedic and Chinese Herbs. Warwick, Queensland:Phytotherapy Press; 1996:69-74. 84 Foster S, Yue CX. Herbal Emissaries: Bringing Chinese Herbs to the West. Rochester, VT: Healing Arts Press; 1992:146–52. 85 Fulder S. The Root of Being. London: Hutchinson and Co; 1980. 86 Graham HN. Green tea composition, consumption, and polyphenol chemistry. Prev Med 1992;21:334–50.