A Guide To Nutritional Supplements For Patients With Diabetes
Nearly 21 million people in the United States have diabetes, according to the Centers For Disease Control and Prevention (CDC). Approximately 6.2 million of these people are not aware they have the disease. The CDC also estimates that over 40 million people have pre-diabetes, a condition that increases the risk of developing type 2 diabetes. Over 20 percent of adults 60 years of age and older have diabetes. “Diabetes is the leading cause of adult blindness, limb amputation, kidney disease and nerve damage,” notes Frank Vinicor, the Director of the CDC’s diabetes program.1 Podiatrists see patients with diabetes on a fairly regular basis. While podiatric physicians do not treat the systemic disease of diabetes, the resultant vascular and neurological complications can certainly come into play with lower extremity complications from the disease. These patients present many challenges when it comes to managing the multi-system effects of diabetes. The diabetic patient population also presents a greater risk of postoperative complications due to vascular and neurological pathology directly attributed to diabetes. Most of the diabetic patients whom podiatrists see are already under the care of their family practitioner or internist when it comes to medications and diet. However, there is a group of patients that we see as podiatrists who may not be diagnosed with diabetes but have some of the disease characteristics that could affect a surgical outcome. There are also patients with diabetes who are under the care of their primary care physicians but do not have good blood glucose control. As podiatric physicians, it behooves us to make sure we do everything in our power to assist these patients in their disease management as it affects their lower extremities. Accordingly, let us take a closer look at self-management tools (see “The Glycemic Index: A Valuable Tool For Self-Management” below) and nutritional supplements that podiatrists can recommend to help these patients maintain better blood sugar control and better peripheral vascular perfusion. The Glycemic Index: A Valuable Tool For Self-Management To prevent diabetic complications, podiatrists may be able to help patients with diabetes by educating them about new clinical information on recommended diets. The glycemic index is one measure people with diabetes can use to help control blood glucose. Jenkins developed the index 25 years ago to measure the rise of blood glucose after consumption of a particular food.2 Researchers determined these glycemic index ranges over a period of time, using multiple types of whole foods. The idea is that the higher the glycemic index number, the greater the rise in insulin as a result of the similar rise in blood sugar. Therefore, the lower the glycemic index of the particular food, the lower the blood glucose level and the corresponding insulin response. While the glycemic index offers a guideline for dietary recommendations for people with either diabetes or hypoglycemia, it should not be the only guideline for maintaining normal blood sugar and insulin levels. For example, while high fat foods like ice cream and sausage may have a low glycemic index, these are not good choices for people with hypoglycemia or diabetes as researchers have shown that a diet high in fat impairs glucose uptake. In the past, many physicians have recommended that patients with diabetes avoid fruits and fructose, which is the primary form of sugar found in fruits. However, recent research challenges this concept. The ingestion of fructose does not cause a rapid rise in blood sugar levels. It needs to be changed to glucose in the liver in order for the body to utilize it fully. Blood glucose levels do not rise as rapidly after fructose consumption compared to other simple sugars. Therefore, there is not a corresponding rise of insulin as there would be with the ingestion of other simple sugars. Fructose, from whole fruit, has a glycemic index of 20 while glucose has a glycemic index of 100. Certainly, the glycemic index has important clinical relevance and can be used as a tool to provide information to patients concerning foods that may rapidly elevate their blood sugar. Clinically, we have seen that foods with a glycemic index of 70 or above have a profound effect on the rapid rise in insulin in blood sugar in patients with diabetes. By stabilizing the patient’s blood sugar levels, utilizing low glycemic index foods and meals in a ratio of 35 percent complex carbohydrates, 30 percent fats (including 21 percent monosaturated fats such as olive oil) and 35 percent protein will result in lower levels of the proteins and lower levels of blood glucose. Research has demonstrated that when the glycemic index of carbohydrates decreases to between 38 and 54, the glycosylated hemoglobin drops by 9 percent and the fructosamine levels decrease by 8 percent. Podiatric physicians should consider recommending the use of the glycemic index to patients with diabetes. There are also books available and lists on the Internet that supply the glycemic index of multiple types of foods. Nutritional Supplements: Separating Hype From Reality Podiatric physicians can assist patients with diabetes by recommending nutritional supplements. Researchers have shown in clinical studies that the addition of key nutrients helps improve blood sugar control and helps prevent or ameliorate many of the major complications of diabetes. While nutritional supplements will never supplant a proper diet, glycemic control and consistent exercise, they can play a valuable adjunctive role in helping patients with diabetes maintain normal blood glucose levels. Certain supplement companies try to provide a wide range of nutritional supplements within one tablet or capsule. Some of these companies state that a single capsule or tablet of a combination of multiple vitamins and minerals would be all that is necessary for augmenting the diet of a patient with diabetes. The problem with the philosophy of “once-a-day multivitamins” is that the patient utilizes the water-soluble vitamins in the tablet within two hours of ingestion. Therefore, one will have a serum spike of the essential vitamin and then a drop in the serum level, which does not aid the patient who has diabetes, who needs a constant therapeutic level of these essential vitamins during the day. When it comes to these patients, they may need to take nutritional supplements three or more times a day in order to have a constant therapeutic level in the bloodstream. Many nutriceutical companies tout their brand or combination as being the best absorbed or the most biologically active form of vitamins and minerals. However, there has been ongoing research on the use of nutritional supplements for the treatment of diabetes in well-controlled trials. Diabetes Care published a systematic review of the current literature on the efficacy and safety of herbal therapies and vitamin/mineral supplements for glucose control in people with diabetes.3 The authors concluded that the herbal extracts from cocina indica and American ginseng showed good glycemic control results. Positive preliminary results from clinical trials demonstrated that gymnema sylvestre, aloe vera momordica charantia and vanadium were also helpful in reducing hyperglycemia. A recent double-blind, placebo-controlled balance crossover study demonstrated that taking 200 mg of oral Panax ginseng significantly reduced blood sugar levels.4 Many herbal and mineral combinations are available for the treatment of patients with hyperglycemia. The right combinations and strengths are important to ensure the successful use of these nutritional supplements. One should only recommend nutritional supplements that come from an FDA-approved manufacturing facility as the FDA approval of these facilities lends more credence to the quality and purity of the products. Also, the efficacy of these products will be consistent when manufactured in this type of pharmaceutical grade facility. Understanding The Effects Of Vitamin Supplements • Thiamin (vitamin B1). Thiamin is the active form of thiamine pyrophosphate, which functions as a cocarboxylase. It is required for the oxidative carboxylase of pyruvate to form active acetate and acetyl coenzyme A. It is also required for the oxidative carboxylase of other alpha-keto acids such as alpha-ketoglutaric acid into keto-carboxylase derived from the amino acids methionine, threonine, leucine, isoleucine and valine. Allicin, a substance found in onions and garlic, combines with thiamine and renders it more absorbable. Thiamine pyrophosphate (TPP) is involved in the oxidation pathway and may be responsible for the energy required for nerve conduction. Diabetic patients, who would normally have a high intake of carbohydrates, need an increase in the amount of thiamine in their diet. The recommended daily allowance (RDA) is 1.0 to 2.4 mg per day. Therapeutic levels of thiamin for patients with diabetes should be in the range of 60 mg per day in divided doses. Many nutriceutical manufacturers provide multivitamin mineral supplements with thiamine in the 60 mg per day therapeutic range. There is very little evidence of thiamine toxicity. In monkeys, the lethal dose is greater than 350 mg/kg body weight. • Riboflavin (vitamin B2). Riboflavin is essential in the activation of vitamin B6 and is involved in converting tryptophan to niacin. Riboflavin is essential for the production of corticosteroids and in the regulation of gluconeogenesis and thyroid enzyme regulation. Vitamin B2 is the component of two major energy enzymes: flavin mononucleotide and flavin adenine dinucleotide. Vitamin B6 is also important in glucose metabolism. Exercise uses glucose stores and can dramatically alter levels of the active coenzyme form of B6.5 The RDA for B2 is 1.2 to 1.6 mg per day and is 1.5 to 1.7 mg/day during pregnancy/lactation. Therapeutic levels of vitamin B2 should be in the range of 60 mg per day. No toxicity due to riboflavin has been found. • Vitamin B6 (pyridoxal-5-phosphate). Vitamin B6, in its active form, is involved in the transamination of ammonia groups to other amino acids. It is also involved in the deamination or removal of amino acids. It can also be useful as an energy source and in the decarboxylation process for the removal of carboxyl (C00H) groups from certain amino acids to form another compound. It is required in the synthesis of neurotransmitters such as serotonin, norepinephrine and histamine from tryptophan, tyrosine and histamine. The RDA requirement for Vitamin B6 is 2 to 2.2 mg per day. It is 5 to 6 mg/day during pregnancy/lactation. The therapeutic level of vitamin B6 is at least 60 mg per day. Toxicity with vitamin B6 has been reported in one case in which a dosage of 200 mg/per day was administered and resulted in peripheral neuropathy. Normally, it would take a dosage of 225 g per day for a few months in order to cause toxic symptoms consisting of numbness and tingling in extremities. The symptoms usually disappear once the patient discontinues the B6 but may linger for a few months if the symptoms are severe. If the patient is on L-dopa for Parkinson’s disease and takes vitamin B6, the vitamin will convert the L-dopa into dopamine outside the blood/brain barrier. This will render the L-dopa ineffective because dopamine cannot pass the blood/brain barrier. If the patient is on Sinemet® (a combination of L-dopa and carbidopa), B6 may actually have a synergistic effect. Carbidopa stops conversion of L-dopa outside the blood/brain barrier. The vitamin B6 would then cross the blood/brain barrier along with the unchanged L-dopa. Once inside the blood/brain barrier, the B6 would then convert the L-dopa into dopamine where the brain could then effectively use it. A Closer Look At Options For Managing Diabetic Neuropathy There is a relationship between elevated levels of homocysteine and diabetic neuropathy in patients with type 2 diabetes mellitus.6 Homocysteine is known to exhibit toxic effects on vascular endothelial cells by increasing oxidation and damaging connective tissues. One may employ nutrients to help reverse the elevated levels of homocysteine in patients with diabetes whether they have peripheral neuropathy or not. The nutrients may be prescribed in the following combination: L-methylfolate 2.8 mg per day, methylcobalamin 2 mg per day and pyridoxal-5-phosphate, 25 mg twice a day. This combination of nutrients is supplied as a prescription tablet that patients may take once or twice a day. Researchers have shown that a high dose of folate increases the bioavailability of nitric oxide, which is essential for several bodily functions and improved endothelial function in patients with type 2 diabetes.7 The short-term oral use of folic acid supplementation enhanced endothelial function in patients with type 2 diabetes. Methylcobalamin has been proven to facilitate myelin node genesis and nerve regeneration in a double-blind study that utilized oral methylcobalamin.8 This study also showed the benefit of using methylcobalamin to regress the symptoms of diabetic neuropathy. Authors have shown that pyridoxal-5-phosphate (vitamin B6), in a dosage of 50 to 100 mg/day, decreases the glycosylation of hemoglobin.9 It is thought that glycosylated hemoglobin may be responsible for the end organ damage resulting from diabetes. Jones and Gonzalez related the usefulness of pyridoxine in the treatment of diabetic neuropathy for podiatric patients.10 It was interesting to note that the neuropathy caused by a vitamin B6 deficiency is indistinguishable from diabetic neuropathy. Much has been written in the podiatry literature on the use of alpha lipoic acid for treating peripheral neuropathy. Lipoic acid is approved in Germany for preventing and treating diabetic neuropathy. The effect may result from the medication’s antioxidant activity. Researchers have shown that lipoic acid replenishes vitamin C and glutathione, and helps recycle vitamin E. Lipoic acid may also help reduce blood glucose and the damaging glycosylation of proteins. Nagamatsu, et. al., demonstrated that lipoic acid improves nerve blood flow, reduces oxygen stress and improves distal nerve conduction in experimental diabetic neuropathy.11 Combining acetyl-L-carnitine and lipoic acid has an added benefit in the treatment of peripheral diabetic neuropathy. A recent randomized, double-blind, placebo-controlled trial with 333 patients examined the use of acetyl-L-carnitine at 1,000 mg per day intramuscularly for 10 days, followed by oral acetyl-L-carnitine at 2,000 mg per day for one year. Nerve conduction velocities dramatically increased by several fold in the acetyl-L-carnitine group compared with the placebo treatment. Acetyl-L-carnitine treatment also significantly decreased painful neuropathies by 39 percent from baseline scores. Study authors stated that acetyl-L-carnitine was a promising treatment for diabetic neuropathy.12 Several nutriceutical companies are offering a combination of acetyl-L-carnitine and alpha lipoic acid for the treatment of diabetic neuropathy. The usual oral doses are 1 to 4 g daily in divided doses. Parenteral doses were between 1 to 21.5 g daily for acetyl-L-carnitine and between 200 and 300 mg per day for lipoic acid. What You Should Know About Other Supplements • Biotin. In an animal study performed by Reddi, DeAngelis, Frank, et. al., biotin improved glucose and insulin tolerances in genetically diabetic KK gamma and KK B1 mice.13 Biotin supplementation reportedly enhances insulin sensitivity and increases the activity of the glucose kinase, the enzyme responsible for the first step in the liver’s utilization of glucose. Kinase concentrations are usually low in patients with diabetes. In Reddi’s study, 16 mg of biotin per day resulted in a significant reduction of fasting blood sugar levels and improvements in blood glucose control among people with insulin-dependent diabetes mellitus.11 Biotin doses of greater than 8 mg per day would require close observation by the attending clinician in order to make sure insulin requirements are adjusted as needed. • Chromium. Trivalent chromium, a trace element, is required for the maintenance of normal blood glucose metabolism. O’Connell demonstrated that chromium deficiency is associated with impaired glucose tolerance, which can be improved with supplementation.14 However, most individuals with diabetes are not chromium deficient. In addition to glucose control, researchers have studied the chromium supplement for its effects on weight control, control of hyperlipidemia and bone density. Trivalent chromium’s action is linked with the glucose tolerance factor (GTF) and reportedly increases the number of insulin receptors, enhancing receptor binding and facilitating insulin action. There is no RDA for chromium. Most nutritional supplements manufactured for consumption in the United States utilize at least 200 µg of chromium polynicotinate, chromium picolinate or chromium enriched yeast. • Cinnamon. Radosevich, Deas, Polansky, et. al., found that bioactive compounds extracted from cinnamon potentiate insulin activity as measured by glucose oxidation in the rat in epididymal fat cell assay.15 These authors recommended further studies in the use of bioactive cinnamon compounds and insulin resistance in adult-onset diabetes. Many nutriceutical companies are now including cinnamon extract in their combinations of vitamins and minerals, which are specifically geared toward reducing blood glucose levels. • Vanadyl sulfate. There have been three non-randomized, single-blind studies on the use of vanadyl sulfate in the treatment of hyperglycemia. Utilizing 100 mg/per day, one placebo-controlled study showed a uniform decrease in fasting blood glucose. There was also reduced hemoglobin A-1C and hepatic glucose production in the subjects tested in the study. Insulin mediated the glucose uptake and there was an increase in insulin sensitivity.3 Many nutriceutical companies are adding vanadyl sulfate to their oral formulas for blood sugar control for patients with diabetes. • Herbal combinations. Medi-Plex Physicians Nutrition Network is the only nutriceutical company in the United States that offers a combination herbal product, Gluco Vita, that has been shown to give significant support to blood sugar balance in the human body. I recommend taking two of these capsules three times a day between meals for maximum absorption and clinical effectiveness. A Guide To Nutriceutical Companies In regard to the products discussed in this article, I recommend the following companies that make nutriceutical supplements. • Medi-Plex Physicians Nutrition Network, 6701 Center Drive West, Suite 1500, Los Angeles, CA 90045. Phone: (800) 292-6006. • Integrative Therapeutics Inc., 825 Challenger Drive, Green Bay, WI 54311-8328. Phone: (800) 931-1790. • Metabolic Maintenance. Phone: (800) 772-7873. • Pamlab, LLC, P.O. Box 8950, Mandeville, LA 70470. Phone: (985) 893-4097. In Conclusion Indeed, there are many alternative and complementary therapies for the treatment of hyperglycemia and peripheral neuropathy. Many podiatric patients are well versed in alternative therapies that are offered on the Internet, in health food stores and other sources. However, not all of these nutriceuticals that are offered on the Internet or in big box stores have the same manufacturing criteria or clinical effectiveness as those that are only available by physician prescription. My patients love the fact that I am able to recommend clinically effective nutriceuticals for their benefit along with podiatric therapies. This value-added service has gained wide acceptance from patients and has generated more patient referrals. Accordingly, it behooves the prudent podiatrist to become knowledgeable with the complementary and alternative therapies that are available for patients with diabetes. There are many reputable companies that offer pharmaceutical grade nutriceuticals, and have clinical support staff available to answer questions regarding indications, contraindications, adverse reactions and dosing (see “A Guide To Nutriceutical Companies” above). Dr. Hahn is in private practice at Trinity Clinic in Bend, Ore. He is board-certified by the American Board of Podiatric Surgery and is a member of the American Association of Naturopathic Physicians.
References 1. National Diabetes Fact Sheet. Centers for Disease Control and Prevention, 2005. 2. Jenkins DJA, Wolever TMS, Taylor RH, et. al. Glycemic index of foods: a physiological basis for carbohydrate exchange. Am J Clin Nutrition 24:362-366, 1981. 3. Khan A, Safdar M, Khan M, Khattak K, Anderson R. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care 26(4):3215-3218, 2003. 4. Reay J, Kennedy D, Scholey A. Single doses of Panax ginseng (G115) reduce blood glucose levels and improve cognitive performance during sustained mental activity. J Psychopharmacol, 19:357-365, 2005. 5. Garrison RH. Nutrition Desk Reference, Keats Publishing, New Canaan, Connecticut. 1985, page 93. 6. Ambrosch A, Dierkes J, Lobmann R, et. al. Relation between homocysteinaemia and diabetic neuropathy in patients with Type 2 diabetes mellitus. Diabetic Medicine 18(3):185-192, 2001. 7. Mangoni A, Sherwood R, Asonganyi B, Swift C, Thomas S, Jackson S. Short-term oral folic acid supplementation enhances endothelial function in patients with type 2 diabetes. Am J Hypertension 18:220-226, 2005. 8. Yaqub B, Siddique A, Sulimani R. Effects of methylcobalamin on diabetic neuropathy. Clinical Neurology Neurosurgery 94(2):105-111, 1992. 9. Solomon LR, Cohen K. Erythrocyte O2 transport and metabolism and effects of vitamin B6 therapy in type II diabetes mellitus. Diabetes 38(7):881-86, 1989. 10. Jones CL, Gonzalez V. Pyridoxine deficiency. J Am Podiatry Assoc. 68:646, 1978. 11. Nagamatsu M, Nickander KK, Schmelzer JD, Raya A, Wittrock DA, Tritchler H, et. al: Lipoic acid improves nerve blood flow, reduces oxidative stress, and improves distal nerve conduction in experimental diabetic neuropathy. Diabetes Care. 18:1160-70, 1995. 12. DeGrandis D, Minardi C. Acetyl-L-carnitine (levacecarnine) in the treatment of diabetic neuropathy: a long-term, randomized, double-blind, placebo-controlled study. Drugs in R&D 3(4):223-31, 2002. 13. Reddi A, De Angelis B, Frank O, et .al. Biotin supplementation improves glucose and insulin tolerances in genetically diabetic KK mice. Life Sci 42:1323-30, 1988. 14. O’Connell B. Select vitamins and minerals in the management of diabetes. Diabetes Spectrum. 14:133-148, 2001. 15. Radosevich J, Deas S, Polansky M, et. al. Regulation of PTP-1 and insulin receptor kinase by fractions from cinnamon: implications for cinnamon regulation of insulin signaling. Hormone Research, 50:177-182, 1998.