Nearly 98 million people in India may have type 2 diabetes by 2030, according to a study published in the ‘Lancet Diabetes & Endocrinology’ journal. There are lots of chemical agents available to control and to treat diabetic patients. However, there is an increasing demand by patients for natural products with antidiabetic activity. Abhishek Dutt Tripathi, Anjali Singh, and K.R.C. Reddy attempt to display and remark some of the most popular nutraceuticals being use as antidiabetic.
The quality of life in terms of income, spending, and lifestyle has improved with economic development. However, it has also thrown up a major challenge in the form of ‘lifestyle diseases’. The first victim of this lifestyle change has been food habits. Consumption of junk food has increased manifold, which has led to a number of diseases related to nutritional deficiencies. Nutraceuticals can play an important role in controlling them. No wonder more and more people are turning to nutraceuticals.
A nutraceutical is a food with a medical-health benefit, including the prevention and treatment of disease. The term was coined in the late1980s by Stephen DeFelice, M.D., founder, and chairman of the Foundation for Innovation in Medicine1. Nutraceuticals also refer to natural functional/medical foods or bioactive phytochemicals that have health-promoting, disease-preventing or medicinal properties. These nutraceuticals normally contain the required amount of vitamins, lipids, proteins, carbohydrates, minerals, or other necessary nutrients, depending on their emphases.
When food is being cooked or prepared using “scientific intelligence” with or without knowledge of how or why it is being used, the food is called “functional food”.
Thus, functional food provides the body with the required amount of vitamins, fats, proteins, carbohydrates, etc. needed for its healthy survival. When functional food aids in the prevention and/or treatment of disease and/or disorder other than anaemia, it is called a nutraceutical. Examples of nutraceuticals include fortified dairy products (e.g. milk) and citrus fruits (e.g. orange juice)
Nutraceuticals and Diabetes
Diabetes mellitus is characterized by abnormally high levels of blood glucose, either due to insufficient insulin production or due to its ineffectiveness. The most common forms of diabetes are type1 diabetes (5%), an autoimmune disorder, and type2 diabetes (95%), which is associated with obesity. Gestational diabetes occurs in pregnancy. As a result of elevated levels of blood glucose, two problems occur: body cells become starved for energy, and, over time, the high glucose levels can damage the nerves, eyes, kidneys, heart and blood vessels. Globally the total number of people with diabetes is projected to rise from 171 million in 2000 to 366 million in 2003. Several medicinal plants have found potential use as hypoglycaemic in the Indian system of medicines, including ayurveda7.
Nutraceuticals have the capability to control diabetes. Nutraceuticals denote foods having a medicinal effect on the health of human beings. According to the American Diabetes Association, if you have the symptoms of developing diabetes then an appropriate change in diet will certainly do wonders for you. Research is also supportive of the benefits of diets high in certain types of fiber for promoting improved post-prandial glucose and insulin responses in normal individuals and in individuals with type 2 diabetes, dyslipidemia, and insulin resistance. The types of dietary fiber that appear to be most significant with respect to insulin resistance include oat fiber and sugar gum, while psyllium has produced mixed results. Coffee is another great nutraceutical. It comprises of chlorogenic acid which acts as an antioxidant. After having food, it aids in slowing down the release of glucose in our bloodstream. A few more popular nutraceuticals include magnesium, chromium picolinate, conjugated linoleic acid, bitter melon, and our beloved cinnamon. These nutraceuticals effectively enhance glucose tolerance as well as insulin sensitivity.
Traditional plant medicines are used throughout the world for a range of diabetic presentations. Herbal drugs are prescribed widely because of their effectiveness, fewer side effects, and relatively low cost. Therefore, investigation on such agents from traditional medicinal plants has become more important20. The present review deals with some selective Indian medicinal plants having pharmacologically established hypoglycaemic potential.
Categories of nutraceuticals and their role in diabetes
Nutraceuticals are non-specific biological therapies used to promote wellness, prevent malignant processes and control symptoms. These can be grouped into the following three broad categories.
- Substances with established nutritional functions, such as vitamins, minerals, amino acids and fatty acids – Nutrients
- Herbs or botanical products as concentrates and extracts – Herbals
- Reagents derived from other sources (e.g. pyruvate, chondroitin sulphate, steroid hormone precursors) serving specific functions, such as sports nutrition, weight-loss supplements and meal replacements – Dietary supplements.
Apart from choosing herbs as part of the natural army against diabetes, vitamins and minerals are also an essential and balancing factor. There is mentioning below the basic vitamins and minerals that our needs especially in case of diabetes. These nutrient classes can be categorized as either macronutrient (needed in relatively large amounts) or micronutrient (needed in smaller quantities). The macronutrients include carbohydrates, fats, protein, and water. The micronutrients are minerals and vitamins.
Carbohydrates: Dietary carbohydrates from cereals, breads, other grain products, legumes, vegetables, fruits, dairy products, and added sugars should provide 50–60% of the individual’s energy requirements. Both the source and the amount of carbohydrate consumed influence blood glucose and insulin responses. When carbohydrate food is eaten there is a corresponding rise and subsequent decrease in blood glucose level known as the glycaemic response. This response is relevant, for example, to appetite control, sports nutrition and those with diabetes. A number of factors influence the rate and duration of the glycaemic response. It depends on:
The specific food
- The type of sugar that forms the carbohydrate
- The nature and the form of the starch as some are more digestible than others
- The cooking and processing methods used
- Other nutrients in the food such as fat or protein
Weight reduction is usually necessary and is the primary dietary aim for people with non-insulin-dependent diabetes. Consuming a wide range of carbohydrate foods is an acceptable part of the diet of all diabetics, and the inclusion of low glycaemic index foods is beneficial as they help regulate blood glucose levels. Most recommendations for the dietary management of diabetes allow a modest amount of ordinary sugar as the inclusion of sugar with a meal has little impact on either blood glucose or insulin concentrations in people with diabetes.
Protein: Current evidence indicates people with diabetes have similar protein requirements to those of the general population – about 0.86 g/kg per day. Although protein plays a role in stimulating insulin secretion excessive intakes should be avoided as it may contribute to the pathogenesis of diabetic nephropathy. Some evidence suggests eating vegetable protein rather than animal protein is better for reducing serum cholesterol29 and managing nephropathy. There are a number of different types of protein supplements include liquid protein supplements, protein powders, and liquid protein shots. There are a number of sources for protein supplements. Some of these sources include Whey, Casein, Soy, Rice, and Egg.
Fat: Numerous studies indicate high-fat diets can impair glucose tolerance and promote obesity, dyslipidemia and atherosclerotic heart disease. Research also shows these same metabolic abnormalities are reversed or improved by reducing saturated fat intake. Current recommendations on the fat intake for the general population apply equally to people with diabetes: reduce saturated fats to 10% or less of total energy intake and cholesterol intake to 300 mg/d or less. Scientific debate continues over which alternative is preferable to saturated fat polyunsaturated fat, monounsaturated fat, or carbohydrate calories. Research suggests monounsaturated fat such as canola, olive, and peanut oils may have beneficial effects on triglycerides and glycemic control in some individuals with diabetes, but care must be taken to avoid weight gain. Omega-3 fatty acids, found in fish such as salmon and mackerel, may reduce serum triglycerides without impairing glycemic control.
Minerals: Chromium (Cr+3) is an essential trace element required for normal glucose metabolism. It appears to act by enhancing insulin’s actions, with increases in the number of insulin receptors, increased binding of insulin to the insulin receptor and increases in activation of the insulin receptor reported. Because chromium is a nutrient, supplements are likely to be beneficial only in those people with chromium deficiencies. Chromium levels in the body tend to decline with age, which may be one factor affecting older people’s risk of developing Type II diabetes. Dosage levels between 100-500 mcg/day have been shown to reduce blood glucose, insulin, and cholesterol.
Vanadium: Research indicates that this mineral acts similarly to insulin in transporting glucose into the cells, and is therefore valuable for both Type I and Type II diabetics. Vanadium supplementation also decreased fasting blood glucose levels, Hemoglobin A1c levels and cholesterol levels 50. Dosages ranging from 45-150 mg/day can be useful for improving fasting glucose levels (how much sugar is in the blood when one wakes up in the morning). Toxicity studies show these dosage levels to be safe and well-tolerated by most people. Some individuals experience mild gastrointestinal distress, either during the first week of use or at higher dosage levels (up to 400 mg/day).
Magnesium: The mineral magnesium functions as an essential cofactor for over 300 enzymes in the body. It is essential for all energy-dependent transport systems, glycolysis, oxidative energy metabolism, and biosynthetic reactions. While this mineral is not directly implicated in the mechanisms of diabetes, it helps to protect patients from complications of the disease. For people with diabetes or heart disease, the recommended daily intake level of magnesium is 1000 mg/day. However, because the actions of calcium and magnesium are so strongly connected, one needs an intake ratio of 2:1 or more – for each 1000 mg of calcium, one should also get 500-1000 mg of magnesium.
Vitamin E: Vitamin E is an essential fat soluble vitamin and functions primarily as an antioxidant. Low levels of vitamin E have been associated with increased incidence of diabetes53 and some research suggests people with diabetes have decreased levels of antioxidants. Additional evidence indicates that people with diabetes may also have greater antioxidant requirements, due to increased free radical production secondary to hyperglycemia. Doses of vitamin E up to 400 IU are generally believed to be safe. Doses over 800 IU may alter blood clotting although supplement trials that have monitored prothrombin times in subjects have noted no increases.
Vitamin C: Research has shown that Vitamin C supplementation may be beneficial to type II diabetes patients. In one study patients took no Vitamin C for the first week, then 1g/day for 4 weeks, followed by 3g/day for a further 4 weeks. The results showed that the mega dose of Vitamin C helped to control blood sugar levels and increased the patient’s anti-oxidant status. There is preliminary evidence that substantial supplements of vitamin C (about 1000 mg daily) may help to prevent or reduce the development of cataracts and nerve disorders that commonly occur in people with diabetes. Such may also inhibit protein glycosylation, which is believed to be important in the development of the long-term complications associated with diabetes.
Biotin: Biotin, a member of the B vitamin complex, is necessary for both metabolism and growth in humans, particularly in the production of fatty acids, antibodies, and digestive enzymes and in tissue metabolism. Importantly, for patients with diabetes, biotin stimulates liver glucokinase activity, increases insulin production, and enhances glucose uptake in muscle cells. Food sources of biotin include organ meats, soy, egg yolks, whole grains, and yeast. There is growing evidence of suboptimum biotin intake in the U.S. population. A recommended dosage level for diabetics is 9 mg/day.
Omega 3 Fatty Acids: Fatty acids are an integral “building block” of our cell walls. In order for glucose to get into our cells and provide energy, that wall must be fluid and flexible. However, the body cannot make omega-3 fatty acids, so must get them from dietary sources. The best sources are fatty fish (such as salmon, mackerel, sardines, herring, and tuna), flaxseed, evening primrose, borage, walnuts, and wheat germ. Omega-3 essential fatty acids (omega 3 EFAs), improve insulin resistance in animal models. Their effect on humans has been equivocal. Available human research has shown a range of outcomes regarding insulin metabolism ranging from some improvement to no change to deterioration of glycemic control in one study. A recommended intake level of flaxseed oil is 1-2 tablespoons/day (or 1/4 cup freshly ground flaxseed).
Alpha-Lipoic Acid: This substance is a potent anti-oxidant, soluble in both fats and water, which means it, can act in virtually all areas of the cell to neutralize free radicals. Alpha-Lipoic acid has been shown to improve insulin resistance in a variety of animal models. Copious anecdotal evidence exists regarding the efficacy of alpha-lipoic acid in restoring insulin sensitivity in type 2 diabetes. Alpha lipoic acid has been demonstrated to inhibit mammalian pyruvate dehydrogenase kinase, thereby providing a possible mechanism for glucose (and lactate) lowering effect in diabetic subjects. Dosage levels of 600-1800 mg/day have been shown to improve the transport of glucose into cells by as much as 63%.
Coenzyme Q10: The importance of this nutrient cannot be overstated, primarily because many of the drugs that are needed for the management of diabetes and/or its complications deplete CoQ10. Coenzyme Q10 (CoQ10) is a promising nutritional intervention for insulin resistance, at least among subjects with hypertension. Singh et al conducted an eight-week randomized, double-blind trial comparing the use of a water-soluble form of CoQ10 (60 mg twice daily) to a vitamin B complex in 59 hypertensive patients. Their results indicated CoQ10 at this dose lowered glucose and fasting insulin levels, suggesting possible improved insulin resistance.
Herbal Dietary supplements: Great attention has nowadays been given to discover the link between dietary nutrients and disease prevention. Large numbers of herbs that had been in use since unknown time have been shown to play a crucial role in the prevention of disease. In addition to the macro and micro-nutrients such as proteins, fats, carbohydrates, vitamins or minerals necessary for normal metabolism, a plant-based diet contains numerous non-nutritive phytoconstituents which may also play an important role in health enhancement. A brief overview of the role of various herbs in disease prevention, with a focus on bioactive components from flaxseeds, garlic, citrus, fruits, soybean, and ginkgo biloba has been given in this part of the nutraceuticals.
Nutraceuticals are food supplements and have nutritional value. All the nutrients discussed in this review have exhibited significant clinical & pharmacological activity. There is an increasing demand by patients to use natural products with antidiabetic activity. The natural products especially herbs are the rich source of nutraceuticals which commonly have significant and negligible side effects than synthetic antidiabetic drugs. The efficacy of hypoglycemic herbs is achieved by increasing insulin secretion, enhancing glucose uptake by adipose and muscle tissues, inhibiting glucose absorption from the intestine and inhibiting glucose production from hepatocytes. A place for nutraceuticals in clinical practice is emerging, but important pharmaceutical and clinical issues need to be addressed by further research.
Functional Foods and Phyto Medicines from Spices
- DeFelice SL. FIM. Rationale and proposed guidelines for the nutraceutical research & education act –NREA. 2002.
- Zeisel SH. Regulation of “Nutraceuticals”. Science.1999; 285:185-86.
- Whitman M. Understanding the perceived need for complementary and alternative nutraceuticals: lifestyle issues. Clin J OncolNurs. 2001; 5:190-94.
- Kalra EK. Nutraceutical-definition and introduction.AAPS PharmSci.2003; 5:2-3
- Expert Committee on the Diagnosis and Classification of Diabetes Mellitus Diabetes Care. Alexandria, Virginia: USA; 2003.
- Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for 2000 and projections for 2030. Diabetes Care.2004; 27:1047.
- Mukherjee Pulok K, MaitiKuntal, Mukherjee Kakali, and Houghton Peter J. Review: Leads from Indian medicinal plants with hypoglycemic potentials. Journal of Ethnopharmacology.2006; 106:1–28.
- Frape DL and Jones AM. Chronic and postprandial responses of plasma insulin, glucose, and lipids in volunteers given dietary fibre supplements.Br J Nutr.1995; 73:733-751.
- Pick ME, Hawrysh ZJ, Gee MI. Oat bran concentrate bread products improve long-term control of diabetes: a pilot study. J Am Diet Assoc. 1996; 96:1254-1261.
- Braaten JT, Scott FW, Wood PJ. High beta-glucan oat bran and oat gum reduce postprandial blood glucose and insulin in subjects with and without type2 diabetes. Diabet Med. 1994; 11:312-318.
- Hallfrisch J, Scholfield DJ, Behall KM. Diet’s containing soluble oat extracts improves glucose and insulin responses of moderately hypercholesterolemic men and women. Am J ClinNutr.1995; 61:379-384.
- Tappy L, Gugolz E, Wursch P. Effects of breakfast cereals containing various amounts of beta-glucan fibers on plasma glucose and insulin responses in NIDDM subjects. Diabetes Care.1996; 19:831-834.
- Rodriguez-Moran M, Guerrero-Romero F, Lazcano-Burciaga G. Lipid- and glucose-lowering efficacy of plant agopsyllium in type II diabetes. J Diabetes Complications.1998; 12:273-278.
- Frati Munari AC, Benitez Pinto W, Raul Ariza Andraca C, Casarrubias M. Lowering glycemic index of food by acarbose and Plantagopsyllium mucilage. Arch Med Res. 1998; 29:137-141
- Fairchild RM, Ellis PR, Byrne AJ. A new breakfast cereal containing guar gum reduces postprandial plasma glucose and insulin concentrations in normal-weight human subjects. Br J Nutr.1996; 76:63-73.
- Landin K, Holm G, Tengborn L, Smith U. Guar gum improves insulin sensitivity, blood lipids, blood pressure, and fibrinolysis in healthy men. Am J ClinNutr.1992; 56:1061- 1065.
- Tagliaferro V, Cassader M, Bozzo C. Moderate guar-gum addition to usual diet improves peripheral sensitivity to insulin and lipaemic profile in NIDDM. DiabeteMetab. 1985; 11:380-385.
- Venkateswaran S and Pari L. Effect of Cocciniaindicaleaves on antioxidant status in streptozotocin-induced diabetic rats. Journal of Ethnopharmacology 2003b; 84:163–168.
- Suba V, Murugesan T, Arunachalam G, Mandal SC, Saha BP. Anti-diabetic potential of Barlerialupulinaextract in rats. Phytomedicine. 2004a; 11:202–205.
- Hathcock J. Dietary supplement: How they are used and regulated, J. Nutrition. 2001; 131:1114-7.
- Nutrition Recommendations, Report of the Scientific Review Committee, Ottawa, Canadian Government Publications Centre, Cat No H49- 42/1990E, 1990.
- Wolever TMS, Jenkins DJA, Vuksan V. Variation in meal fat does not affect the relative blood glucose response of spaghetti in subjects with type 2 diabetes. Diabetes NutrMetab.1992; 5:191.
- Wolever TMS, Bolognesi C. Source and amount of carbohydrate affect postprandial glucose and insulin in normal subjects. J Nutr.1996; 126:2798.
- WHO/FAO Carbohydrates in human nutrition. FAO food and nutrition paper no. 66. FAO, Rome: 1998.
- Rimm EB, Ascherio A, Giovannucci E. Vegetable, fruit and cereal fiber intake and risk of coronary heart disease among men. J AMA.1996; 275:447.
- Franz MJ. Protein, metabolism and effect on blood glucose levels.The Diabetes Educator, 23.1997; 6:643.
- Nuttall FQ, Gannon MC. Plasma glucose and insulin response to macronutrients in nondiabetic and NIDDM subjects.Diabetes Care.1991; 14:824.
- Brenner BM, Meyer TW, Hostetter TH. Dietary protein intake and the progressive nature of kidney disease, the role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation and intrinsic renal disease. New Engl J Med. 1982; 307:652.
- Anderson JW, Johnstone MB, Cook-Newell ME. Meta-analysis of the effects of soy protein intake on serum lipids, New Engl J Med, 1995; 333:276.
- Kontessis P, Jones S, Dodds R. Renal, metabolic and hormonal responses to ingestion of animal and vegetable proteins. Kidney Int. 1990; 38:136.
- Anderson JW, Blake JE, Turner J. Effects of soy protein on renal function and proteinuria in patients with type 2 diabetes. Am J ClinNutr. 1998; 68:1347.
- Summary of the second report of the National Cholesterol Education Program expert panel on detection, evaluation and treatment of high blood cholesterol in adults (Adult Treatment Panel II), JAMA. 1993; 269:3015.
- Prunell JG, Brunzell JD. The central role of dietary fat, not carbohydrate, in the insulin resistance syndrome.CurrOpinLipidol.1997; 8:17.
- Reaven GM. Do high carbohydrate diets prevent the development or attenuate the manifestations (or both) of syndrome X? A viewpoint strongly against.CurrOpinLipidol.1997; 8:23.
- Garg A. High-monounsaturated-fat diets for patients with diabetes mellitus, a meta-analysis. Am J ClinNutr.1998; 76:577.
- National Research Council. Recommended Dietary Allowances. 10th ed. Washington DC: National Academy Press; 1989.
- Anderson RA. Chromium, glucose intolerance and diabetes. J Am Col Nutr. 1998; 17:548-555.
- Food and nutrition Board, Institutes of Medicine. Dietary reference intakes for vitamin A, vitamin K, boron, chromium, copper, iodine, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington DC: National Academy Press; 2001. p. 197-223.
- Sarubin A. The Health Professional’s Guide to Popular Dietary Supplements, Chicago, IL: The American Dietetic Association; 2000.
- Anderson RA. Nutritional Factors influencing the glucose/insulin system: chromium. J Am Col Nutr. 1997; 16:404-410.
- Vincent JB. Quest for molecular mechanism of chromium action and its relationship to diabetes.Nutr Rev. 2000; 58:67-72.
- Mertz W. Interaction of chromium with insulin: a progress report. Nutr Rev. 1998; 56:174-177.
- Vincent JB. Elucidating a biological role for chromium at a molecular level.AccChem Res. 2000; 53:503-510.
- Wyn Snow, Managing Editor. With Diabetes Surging Some Look For Alternative Treatment. 20 October 2006.
- Halberstam M, Cohen N, Shlimovich P, Rossetti L, Shamoon H. Oral vanadylsulfate improves insulin sensitivity in NIDDM but not obese nondiabetic subjects. Diabetes.1996; 45:659-666.
- Cohen N, Halberstam M, Schilmovich P, Chang CJ, Shamoon H, Rosetti L. Oral vanadylsulfate improves hepatic and peripheral insulin sensitivity in patients with non-insulin dependent diabetes mellitus. J. Clin. Invest. 1995; 95:2501-2509.
- Boden G, Chen X, Ruiz J, Van Rossum GD, Turco S. Effects of vanadylsulfate on carbohydrate and lipid metabolism in patients with non-insulin dependent diabetes mellitus. Metabolism.1996; 45:1130-1135.
- Goldfine A, Simonson D, Folli F, Patti ME, Kahn R. Metabolic effects of sodium metavanadate in humans with insulin-dependent and non-insulin dependent diabetes mellitus in vivo and in vitro studies. J. Clin. Endocrinol.Metab.1995; 80:3311-3320.
- De Valk H. Magnesium in diabetes mellitus.J of Med. 1999; 54:139-146.
- White JR, Campbell RK. Magnesium and diabetes: a review. Annals of Pharmacotherapy.1993; 27:775-780.
- Salonen JT, Nyyssonen K, Tuomainen TP, Maenpaa PH, Korpela H, Kaplan GA, Lynch J, Helmrich SP, Salonen R. Increased risk of non-insulin-dependent diabetes mellitus at low plasma vitamin E concentrations: a four year study in men. Br Med J. 1995; 311:1124-1127.
- Jain K, and McVie R. Effect of glycaemic control, race (white versus black) and duration of diabetes on reduced glutathione content in erythrocytes of diabetes patients. Metabolism.1994; 43:306-309.
- Chuchi E, Odetta P, Prando R. Relationship between glutathione and sorbitol concentrations in erythrocytes from diabetic patients. Metabolism.1996; 45:611-613.
- Rema M, Mohan V, Bhaskar A, Shmmugasundaram KR. Does antioxidant stress play a role in diabetic retinopathy? Indian J Opthamol.1995; 43:17-21.
- Wolff SP, and Dean RT. Glucose autoxidation and protein modification: the potential role of autoxidative glycosylation in diabetes.Biochem J. 1987; 245:243-250.
- Sharma A, Kharb S, Chugh SN, Kakkar R, Singh GP. Evaluation of oxidative stress before and after control of glycemia and after vitamin E supplementation in diabetic patients.Metabolism.2000; 49:160-162.
- Ceriello A, Bortolotti N, Motz E, Crescentini A, Lizzio S, Russo A, Tonutti L, Taboga C. Meal-generated oxidative stress in type 2 patients. Diabetes Care.1998; 21:1529-1533.
- Park HS and Lee YM. Effects of vitamin C supplementation on blood sugar and antioxidative status in types II diabetes mellitus patients.TaehanKanhoHakhoe Chi. 2003; 33 (2):170-178.
- Vitamin and mineral supplementation in diabetes: a review Nutrition Research Newsletter, Oct; 1992.
- Dakshinamurti K, Tarrago-Litvak L, Hong HC. Biotin and glucose metabolism. Can J Biochem. 1970; 48:493-500.
- Dakshinamurti K, Cheah-Tan C. Biotin-mediated synthesis of hepatic glucokinase in the rat. Arch BiochemBiophys. 1968; 127:17-21.
- Furukawa Y. Enhancement of glucose-induced insulin secretion and modification of glucose metabolism by biotin. Nippon Rinsho.1999; 57:2261-2269.
- Wang ZQ, Zhang XH, Cefalu WT. Chromium picolinate and biotin enhance glycogen synthesis and glycogen synthase gene expression in human skeletal muscle culture [abstract]. Diab Res ClinPract.2000; 50:395.
- Fernadez-Mejia C. Pharmacological effects of biotin. J NutrBiochem.2005; 16:424-427.
- Luo J, Rizkalla SW, Boillot J. Dietary (n- 3) polyunsaturated fatty acids improve adipocyte insulin action and glucose metabolism in insulin resistant rats: relation to membrane fatty acids. J Nutr.1996; 126:1951-1958.
- Jacob S, Streeper RS, Fogt DL. The antioxidant alpha-lipoic acid enhances insulinstimulated glucose metabolism in insulinresistant rat skeletal muscle. Diabetes 1996; 45:1024-1029.
- Streeper RS, Hendrickson EJ, Jacob S. Differential effects of lipoid acid stereoisomers on glucose metabolism in insulin-resistant skeletal muscle. Am J Physiol. 1997; 273:E185- E191.
- Korotchkina LG, Sidhu S, Patel MS. R-lipoic acid inhibits mammalian private dehydrogenase kinase. Free Radic. Res. 2004; 38:1083-1092.
- Singh RB, Niaz MA, Rastogi SS. Effect of hydro soluble coenzyme Q10 on blood pressures and insulin resistance in hypertensive patients with coronary artery disease. J Hum Hyper tens. 1999; 13:203-208.