Complementary medicine, also known as complementary and alternative medicine, alternative medicine, functional medicine, and integrative medicine, is re-emerging as one of the fastest growing fields in medicine today. A 1997-1998 national survey showed that 57% of individuals with diabetes reported using complementary and alternative medicine therapies during that year; 35% used complementary and alternative medicine specifically for their diabetes. Individuals with chronic disease often turn to complementary and alternative medicine therapies as adjuncts to standard medical treatment. It is noteworthy, however, that approximately 40% of these patients do not discuss complementary and alternative medicine therapies with their physicians. Of those who do report complementary and alternative medicine use, only 35% of all self-reported supplements are documented in the patient’s chart. Given that several herbs and supplements have properties that augment or attenuate pharmaceutical agents, a knowledge of complementary and alternative medicine treatments for diabetes is imperative.

The list of modalities considered “complementary and alternative medicine” is extensive. Included in this chapter are some of the major therapies of the Naturopathic medical system including lifestyle issues, nutritional supplements, and botanical medicine. Portions of other well-known and well-studied medical systems, such as Ayurveda and Chinese medicine, are included in the botanical section.

A basic tenet of most complementary and alternative medicine medical systems views the individual as a whole: a somatic-psycho-social-emotional-spiritual being. To ignore or minimize these factors and treat simply the disease and its symptoms results in less than optimum care. It is the package of care, rather than the specific modality, that promotes healing and well-being.

Lifestyle

While diet and exercise are lifestyle choices that have obvious impact on diabetes (indeed, in most cases they can hardly be considered complementary and alternative medicine), less apparent dietary topics and practices such as spirituality, social support, stress, and smoking can have profound effects on the disease and on the individual.

Diet

Standard dietary recommendations are well described. However, special mention needs to be made regarding fats and type 2 diabetes. In an extensive review, it was found that quality of fat was essential in glucose metabolism. Polyunsaturated fats and long-chain omega-3 fatty acids were found to be beneficial, while saturated fats and trans fats were detrimental to glucose metabolism and insulin resistance. Indeed, some of the adverse effects of a high fat diet can be ameliorated with omega-3 fatty acids, and an inverse relationship has been shown between vegetable fats and risk of diabetes. It is important that the quality as well as the quantity of fats are addressed, as all fats are not created equal.

Cow’s milk has been implicated in the development of type 1 diabetes. Elevated IgG antibodies to bovine serum albumin were found to average seven times higher in children with diabetes than their healthy counterparts. This, in conjunction with viral exposure, may lead to a cross reaction with the p69 surface cell antigen on beta cells, leading to release of interferon gamma and induction of the beta-cell surface antigen. While these results are controversial, it seems that breast milk should be favored over cow’s milk, at least during the first six months of life.

Smoking

Smoking, while deleterious on many counts, has particular influence on carbohydrate and lipid metabolism. In a group of insulin treated diabetics, smokers had a 15-20% higher insulin requirement and serum triglyceride concentration than their nonsmoking counterparts; this went as high as 30% in heavy smokers. While complete abstinence appears to decrease insulin resistance, smoking cessation methods that employ nicotine (gums, patches) decrease insulin sensitivity. The degree of insulin resistance is correlated to the extent of nicotine used. While encouraging patients to quit smoking is always recommended, care must be taken when prescribing patches and gums to aid this process.

Stress

Acute stress, associated with fight-or-flight response, is accompanied by clear and adaptive severe insulin resistance, quickly reversible with the removal of the stressor. Studies have shown, however, that psychosocial stress may be associated with continued insulin resistance.

Cortisol, a major stress hormone, might contribute to insulin resistance by its tendency to oppose the action of insulin, however, the relationship remains unclear. Evidence suggests that consistently elevated levels of cortisol greatly inhibit nonhepatic glucose utilization.

Social Support

Unlike other disease states, diabetes has a significant impact on the social unit of the patient, in addition to the patient themselves. Diet and exercise, the cornerstones of glucose control, will be affected by the support network of the individual. Change in the habits of people with diabetes will often be intimately tied, for better or worse, to the support of their families, colleagues, and health care systems.

A field test of a one-year program of education and support in Sweden, including ongoing counseling, examined 100 patients with type 2 diabetes. At the study onset, 51% of participants had HbAlc levels at or below 6.5%. After 12 months of education and counseling, 63% had HbAlc levels within this range. Interestingly, participants whose diabetes was diet controlled and rated their loneliness as high were more successful in lowering their HbAlc levels than their non-lonely counterparts. This emphasizes the critical need for social network (i.e., family) education, in conjunction with patient education.

Spirituality

Prayer and religious practice, a cornerstone of illness treatment for millennia, have been largely disregarded in modern medical practice. Recently, however, spirituality has been receiving attention as an adjunct to health care, particularly in the area of immune function. In diabetics, C-reactive protein — an acute inflammatory marker levels are known to be higher than in nondiabetics. C-reactive protein has been tied to cardiovascular disease, a common sequelae of diabetes.

A recent cross-sectional survey of 556 diabetics examined attendance at religious services and C-reactive protein levels. Those who did not regularly attend religious service were more likely to have elevated C-reactive protein than those who attended religious services. After adjusting for demographic variables, health status, smoking, social support, mobility, and BMI, the association between religious attendance and C-reactive protein remained significant for respondents with diabetes.

Conclusions

The psychosocial-emotional factors in diabetes can and should be addressed in caring for the individual. While maintenance of glycemic control is the ultimate goal, the well-being and quality of life of the patient must be addressed as well.

Nutritional supplements

Several nutritional components have an effect on insulin resistance and diabetic control. Further, diet, along with medications, may affect micronutrient status in diabetic populations, leading to complications in their glucose control and in general health. Common vitamins, minerals, and nutrients that affect diabetes are discussed, as well as nutrient status affected by diabetes medications.

Vitamins

Minerals

Nutrients

Botanical Medicine

Conclusions

It should be emphasized that while some of the most common modalities of complementary and alternative medicine are presented, Naturopathic medicine, similar to Native American, Ayurvedic, or Chinese medical systems, does not operate solely by treating the disease. Instead, the emphasis is on treating the whole person. An individual with diabetes, for example, would likely receive some of the treatments outlined in this chapter. However, treatment would be individualized to that particular person, and other modalities such as homeopathy, counseling, acupuncture, bodywork (manipulation, hydrotherapy), and/or energy work (Reiki or another healing touch therapy) would be applied as well. It is precisely this individualization of treatment that make complementary and alternative medicine medical systems so difficult to study in the reductionistic paradigm that guides current medical thinking. With time and understanding, however, medical systems rather than single treatments are beginning to be examined; it is hoped that this will continue in the future.

TABLE. Less Well-Studied Botanicals that May Benefit Diabetes

Herb	Effects
Aloe vera	FBS and triglycerides in type 2 with or without standard anti-diabetic agents; hypoglycemic effects in type 2 and animal models; decreased FBS and HbAlcin type 2
Salt bush (Atriplex halimu)	Improved blood glucose regulation and glucose tolerance in type 2; prevents diabetes in sand rats
Konjac (Amophophallus Konjac C. koch)	Reduced plasma cholesterol, LDL, total: LDL ratio, fasting glucose in type 2 on oral hypoglycemics
Cinnamon (Cinnamomum cassia)	Decrease serum glucose, triglycerides, cholesterol, LDL in type 2
Ivy gourd (Coccinia indica)	Change in glycemic control better than conventional drug in type 2; blood glucose lowering in animals
Horsetail (Equisetum myriochaetum)	Decreased blood glucose, no change in insulin following OGTT in type 2
Fig leaf (Ficus carica)	Decrease in postprandial glucose and insulin requirement in type 1; short- and long-term hypoglycemic effects in animals
Ginkgo biloba	Improves blood flow, thereby | sequelae of diabetes
Holy basil (Ocimum sanctum)	Positive effects on fasting and postprandial glucose in type 2; hypoglycemic effects in animal models
Nopal (Opuntia streptacantha)	Decreased fasting glucose and insulin levels in type 2; decrease postprandial glucose and HbAlc with synergistic effects with insulin in animal models
Oolong tea	Decreased concentration of plasma glucose and fructosamine in type 2 or hypoglycemics
Psyllium (Plantago ovata)	Total cholesterol, | LDL, | postprandial glucose rise
Pterocarpus marsupium	Prevents beta-cell damage in rats; regenerates functional pancreatic bets-cells in animals
Milk thistle (Silibum marianum)	Improved glycemic control in cirrhotic type 2 patients
Zygophyllum gaetulum	Short- and long-term reduction in blood glucose, normoglycemia without change in body weight in type 2

 

 

 

Vitamins are vital for life, and, ideally, should be maintained in adequate levels in the foods we eat. With over-farming and genetic modification of foods, the vitamin and mineral content today may not supply the nutrients of the foods past, or even meet what is necessary for optimal health. Add in fast foods, convenience foods, and high fat and sugar choices (some very cleverly disguised), and the ability to meet nutritional requirements becomes questionable.

A large longitudinal study found that adults who used vitamin supplements were 24% less likely to develop diabetes than those who did not. The protective effect of vitamins remained when adjusted for age, race or ethnicity, education, cigarette smoking, systolic blood pressure, use of antihypertensive medication, serum cholesterol, body mass index, exercise, alcohol consumption, fruit and vegetable intake, percent calories from fat, and total energy intake. Clearly, vitamins are an important part of health maintenance.

Vitamin B₃ (Niacin, Niacinamide, Nicotinamide)

Niacin plays an important role in fat, cholesterol, and carbohydrate metabolism. It is an essential component of the glucose-tolerance factor, giving it a key role in hypoglycemia and diabetes. Niacin has been shown to be deficient in people with diabetes.

Niacinamide, a water-soluble amide of nicotinic acid, has been used successfully to prevent or delay the onset of type 1 diabetes, lowering the incidence from 15-20 per 100,000/year to 8 per 100,000/year. Treatment with high-dose niacinamide appears to delay rather than completely reverse disease development in those with preexisting type 1 diabetes. However, treatment of ‘at risk’ groups, in the majority of studies, shows promise in disease prevention.

Lipid profiles in people with diabetes have been improved with niacin supplementation. Niacin has been shown to increase HDL, decrease triglycerides, and decrease LDL in patients with or without diabetes. HbAlc levels remained unchanged in this study, however, another study found extended release niacin improved both HbAlc and lipid profile in diabetics.

Self-medication of high-dose niacin should be discouraged. Flushing, stomach irritation, and hepatic damage may occur with high doses. In normal individuals, niacin has been known to cause insulin resistance. Because of the capacity to disrupt blood sugar control, diabetics taking any form of niacin must monitor their glucose closely.

Vitamin B₆ (Pyroxidine), B_n (Cobalamin), and Folk Acid (Folate)

Vitamins B₆ and Bi₂ have been shown to be deficient in people with diabetes, especially those with diabetic neuropathy. Further, B₁₂ absorption is reduced by metformin. B₆ prevents the glycosylation of proteins, and may be a safe treatment for gestational diabetes. Studies have shown that folate, B₆, and Bi₂ reduce homocysteine levels in diabetics.

Biotin

Biotin supplementation has been shown to enhance insulin sensitivity and increase the activity of glucokinase. Biotin significantly lowers fasting blood sugar and improves glucose control in both type 1 and type 2 diabetes. Insulin requirements must be monitored with high-dose biotin supplementation.

Vitamin C (Ascorbic Acid)

Because the transport of vitamin C into cells is facilitated by insulin, it is often deficient in people with diabetes. High doses of vitamin C have been found to inhibit aldose reductase, inhibiting the conversion of D-glucose to d-sorbitol, then to fructose. Left unchecked, sorbitol and fructose accumulate in cells, causing damage to glucose insensitive tissues: the eye lens, renal glomeruli, and peripheral nerves, exacerbating many of the common complications of diabetes.

Vitamin E

Vitamin E appears to play a significant role in preventing diabetes. In a 4-year prospective study, a low plasma vitamin E was associated with a 3.9-fold increase in risk of diabetes. A 1 µmol/l decrement in serum vitamin E corresponded with a 22% increment in diabetes risk. Supplementation of vitamin E not only improves the action of insulin, but also has a number of beneficial effects that may prevent long-term complications of diabetes.

Like vitamins, minerals are essential to life, and theoretically should be available from foods. Since most multivitamins also contain minerals, it may be presumed that the decrease in diabetic incidence and complications seen with vitamin supplementation may include minerals as well. Several specific minerals, however, bear further mention.

Chromium

Trivalent chromium (Cr3) is a key constituent of glucose-tolerance factor, and deficiency has been linked to decreased glucose tolerance, increased serum insulin levels, and decreased number of insulin receptors. There is evidence that marginal chromium deficiency is common in the United States.

Chromium is a part of a glucose/insulin system that maintains homeostatic control of blood glucose. Cr3 has also been shown to have a positive influence on individuals with no diabetic symptoms. Serum chromium levels in healthy individuals were found to be inversely related to insulin peaks in response to a glucose challenge. In people with diabetes, however, levels did not fluctuate with respect to insulin.

Chromium deficiency has been associated with hyperglycemia in test animals as well as humans, and is reversible by supplementation. It is effective in treating various types of diabetes, including type 1 and 2, gestational, and steroid-induced. Treatment of type 2 diabetes with Cr3 has led to improvement in blood glucose, insulin, and HbAlc levels in a dose-dependent manner. Higher Cr3 doses also resulted in a decrease in cholesterol levels.

While many studies show positive effects with chromium supplementation, the results are mixed. Further, some concern exists regarding high doses and renal dysfunction, including decreased thirst, fatigue, and urinary frequency. Other studies did not replicate this finding at the same dose; no changes in renal or hepatic function were found by laboratory testing. The Drug-Induced Nutrient Depletion Handbook states that side effects and toxicity with chromium supplementation are virtually nonexistent in humans.

Diets high in simple sugars increase urinary excretion of chromium, but show no change in absorption rates. Antacids have been found to decrease absorption.

Magnesium

Hypomagnesemia is common in diabetes. Deficiency can potentially cause states of insulin resistance, and supplementation may prevent some of the complications of diabetes such as retinopathy and heart disease.

Magnesium levels are related to insulin resistance in type 1 and type 2 diabetes, as well as nondiabetics. Between 25% and 48% of type 2 diabetics have been shown to have low magnesium levels.

The research on magnesium supplementation and glycemic control is mixed. Two trials showed a decrease in fasting plasma glucose and an increase in postprandial insulin. Three other trials did not show a change in blood glucose or HbAlc level. However, magnesium deficiency in people with diabetes is not under dispute. Given that magnesium toxicity is rare, it would seem wise to consider supplementation. Caution should be used, as high doses may cause diarrhea.

Potassium

A high potassium diet has several positive results for diabetes control: it yields improved insulin sensitivity, responsiveness, and secretion; it replaces potassium lost by exogenous insulin administration; and it reduces the risk of heart disease, atherosclerosis, and cancer. A potassium-depleted diet was found to lead to insulin resistance at postreceptor sites, reversible when potassium was resupplied.

Diet is the preferred method of increasing potassium intake, as supplementation with potassium salts can cause nausea, vomiting, diarrhea, and ulcers. Further, kidney disease can result from potassium toxicity in people with diabetes, so supplementation other than dietary should be used with care.

Vanadium (Vanadyl Sulfate)

Vanadium is a trace mineral believed to regulate fasting blood sugar and improve sensitivity to insulin. It is thought to be insulin-mimetic, and upregulate insulin receptors.

In three small studies, vanadium has been shown to decrease fasting blood sugar in people with diabetes; two of these also reported improvement in HbAlc and insulin sensitivity. Beneficial effects remained after cessation of active treatment. No change in insulin sensitivity was found with supplementation in obese nondiabetics.

Gastrointestinal discomfort was reported by many subjects, however, organically chelated vanadium compounds cause less irritation than vanadium salts.

Zinc

Zinc is involved with the synthesis, secretion, and utilization of insulin. It also exerts a protective effect against beta-cell destruction. People with diabetes are prone to insulin depletion due to excess excretion, and zinc supplementation has been shown to improve insulin levels in both type 1 and type 2 diabetes.

 

There are several nutritional components beyond vitamins and minerals that either have an affect, or are affected by diabetes. Further, oral hypoglycemics and insulin may deplete some of these essential nutrients, warranting supplementation.

Essential Fatty Acids

Essential fatty acids , including omega-3 (n-3), omega-6 gamma linoleic acid, eicosapentaenoic acid, and do-cocsahexaenoic acid have been studied extensively for their beneficial effects on cholesterol, triglycerides, blood pressure and cardiovascular disease, autoimmune disease, and inflammation. Several compounds have been shown to be particularly relevant to diabetes, beyond their cardiovascular protective effects.

Diabetes, both human and experimental, has been associated with disturbances in Essential fatty acids metabolism; in particular, the conversion of linoleic acid to gamma linoleic acid is inhibited. Linoleic acid shares functional similarities to potent insulin sensitizers, and has been shown to normalize impaired glucose tolerance and improved hyperinsulinemia in animal studies. Gamma linoleic acid, however, is an important component of diabetic complications, particularly neuropathy. In a large multicenter trial, gamma linoleic acid supplementation was provided in the form of evening primrose oil to patients with diabetic neuropathy. Following 1 year of treatment, all symptoms of neuropathy improved. Sources of gamma linoleic acid include evening primrose oil, borage oil, and black currant oil.

Fish oils are an important source of long-chain n-3 fatty acids, eicosapentaenoic acid, and do-cocsahexaenoic acid. The ability of fish oil to enhance the rate of glycogen storage allows skeletal muscle to increase its uptake of glucose, even under conditions where fatty acid oxidation is accelerated. Fish oil enhances insulin secretion by incorporation of n-3 fatty acids into the plasma membrane. This reduces the concentration of amino acids in the plasma membrane, decreasing the production of prostaglandin 2 (PGE2) which, in turn, suppresses the production of cAMP, a well-known enhancer of glucose-induced insulin secretion. Consequently, fish oil enhances insulin secretion from beta cells, regulating blood sugar.

Fish oils have biological properties of potential relevance for the prevention of type 1 diabetes. One large case control study found that cod liver oil, given in the first year of life, was associated with significantly lower risk of type 1 diabetes.

In type 2 diabetes, studies have shown mixed results. One study examined established type 2 diabetics, providing a diabetic diet along with eicosapentaenoic acid and do-cocsahexaenoic acid supplements, or diet alone. Essential fatty acids supplementation resulted in significantly greater improvement in glycemic status, blood pressure, and lipid profiles, as well as reduction in measures of oxidative stress. In other studies, supplementation with fish oils resulted in no change in either fasting serum insulin levels or insulin sensitivity, and one study found an increase in fasting blood glucose following fish oil intervention. However, given the proven vascular benefits of EFAs, with careful monitoring supplementation may be indicated.

Medium chain triglycerides are a component of many foods, with coconut and palm oils being the dietary sources with the highest concentrations. In an inpatient setting, an experimental diet containing 78% of fat calories as Medium chain triglycerides (31% of total energy intake) increased glucose metabolism in patients with type 2 diabetes. In five outpatients with type 2 diabetes, an experimental diet containing 18% of calories from Medium chain triglycerides led to a slight reduction in postprandial blood sugar and no effect on fasting blood sugar. While promising, the role of Medium chain triglycerides in the management of diabetes remains to be decided.

Blood lipid levels should be monitored when supplementing with EFAs. While the results are mixed, and several studies have shown improved lipid levels, but one study found an increase in cholesterol when supplementing people with type 1 diabetes with n-3 fatty acids.

Alpha Lipoic Acid (Thioctic Acid)

Alpha lipoic acid is a naturally occurring thiol, synthesized in the liver. It is a potent antioxidant, a cofactor in many enzymatic complexes, and may play a role in glucose oxidation. Alpha lipoic acid has been shown to improve insulin resistance in a number of animal models, and experimental trials have indicated usefulness in insulin resistance, when delivered both parenterally and orally.

Insulin sensitivity and glucose effectiveness following oral glucose-tolerance test was performed on lean and obese people with type 2 diabetes. Alpha lipoic acid treatment was associated with increased glucose effectiveness in both lean and obese groups, while higher insulin sensitivity and lower fasting glucose were significantly changed in lean subjects only. In another study, blood glucose levels following Alpha lipoic acid supplementation were not changed, however changes in coagulation factors and marked lipid lowering were seen.

A dosage study of Alpha lipoic acid showed a mean increase of 21% in insulin-stimulated glucose disposal in treated subjects, with no significant differences between dosage levels. A relatively low dose, therefore, is sufficient to produce effects.

Coenzyme Qho (Ubiquinone)

Coenzyme Cho (CoQio) is a cofactor in the mitochondrial electron transport chain. Because an adequate supply of energy is essential for the health of virtually all human tissues, CoQio is a vital nutrient. Many recent studies have demonstrated the effectiveness of CoQio in maintaining cardiovascular health.

Several studies have explored the role of CoQio in diabetes. Administration of C0Q7 (a nutritionally equivalent analog of C0Q10) resulted in fasting blood sugar level declines of at least 30% in 31% of the patients. A second study showed improvement in pain and paresthesias in diabetic neuropathy. Several negative studies, however, have indicated that beneficial effects of C0Q10 administration may not be apparent in the short term.

Many of the oral hypoglycemics and all of the lipid-lowering statins deplete C0Q10. Given its known beneficial cardiovascular effects, and emerging effects on glucose control, supplementation in people with diabetes should be considered.

TABLE . Oral Hypoglycemics, Exogenous Insulin, and Nutrient Depletion

Hypoglycemic agent	Nutrient depleted	Potential effects
Acarbose (Precose)	Coenzyme Qio	Congestive heart failure, high blood pressure, angina, mitral valve prolapse, stroke, cardiac arrhythmias, cardiomyopathy, lack of energy, gingivitis, weakened immune system
Acetohexamide (Dymelor)
Glimepride (Amaryl)
Glipizide (Glucotrol)
Glyburide (Micronase)
Tolazamide (Tolinase)
Metformin (Glucophage)	Folic acid	Homocysteine, megaloblastic anemia, headache, fatigue, hair loss, anorexia, insomnia, nausea, diarrhea, f infections
	B12	Fatigue, peripheral neuropathy, macrocytic anemia, confusion, depression, memory loss, poor blood clotting, dermatitis, anorexia, nausea, vomiting
Insulin	K+	Cardiac arrhythmias, poor reflexes, weakness, fatigue, thirst, edema, constipation, dizziness, mental confusion, nervous disorders

Conclusion

This list of nutritional supplements is not meant to be exhaustive. Several other substances, including beta carotene, calcium, manganese, L-carnitine, and glutathione, have shown promise in the treatment of diabetes.

The standard medications for glycemic control can and do influence nutritional status. Table  Oral Hypoglycemics, Exogenous Insulin, and Nutrient Depletion presents the most commonly prescribed diabetes medications, their effect on nutritional substances, and the potential consequences.

There are literally thousands of herbal compounds available and beneficial for various health conditions. Most of the herbs described in this section have been used for centuries, and are just now beginning to be considered in mainstream medicine as options for diabetic control. As testing of botanicals increase, more use of the ancient treatments may be seen.

This section, like the nutritional supplements, cannot be considered exhaustive. The most rigorously studied herbs with the longest and most effective history of use are discussed, with contraindications and interactions presented in tabular form. A table with less well-studied, yet promising, treatments follows.

Bitter Melon (Momordica charantia)

Bitter melon is indigenous to tropical areas in Asia, India, South America, and Africa. It has been used widely in folk medicine as a treatment for diabetes. Theoretical mechanisms of action include increased insulin secretion, tissue glucose uptake, liver muscle glycogen synthesis, glucose oxidation, and decreased hepatic gluconeogenesis. The blood sugar lowering capabilities have been clearly established in clinical trials and experimental models.

Charantin, an active component of bitter melon, is a more potent hypoglycemic agent than tolbutamide, a first generation sulfonylurea. It also contains an insulin-like polypeptide, structurally and pharmacologically comparable to bovine insulin, which lowers blood sugar levels with fewer side effects than exogenous insulin injections.

Positive effects have been shown using bitter melon. One study showed 73% of people with type 2 diabetes had improved glucose tolerance with bitter melon juice. Another small study showed a 54% decrease in postprandial blood sugar and a 17% reduction in glycosylated hemoglobin with an aqueous extract. No adverse effects have been reported in human studies.

Bitter melon may have additive effects when taken with other glucose-lowering agents. While capsules are available, the juice or extract form has been used in most studies. However, as the name implies, the juice is extremely bitter and may be difficult to make palatable.

Bilberry (Vaccinium myrtillus)

Leaves of the bilberry plant were widely used for diabetic treatment before the availability of insulin. In addition, the berries, containing anthocyanidins, have beneficial effects on microvascular abnormalities common in diabetes.

Bilberry has been shown to lower plasma glucose and triglycerides in animals. In humans, it has been shown to improve retinopathy and normalization of collagen deposition. Interestingly, a recent study of mulberry, another rich source of anthocyanidins, compared it to the standard antidiabetic medication glibenclamide. Patients with mulberry therapy significantly improved their glycemic control over those on glibenclamide treatment. Mulberry also significantly decreased serum total cholesterol (12%), triglycerides (16%), plasma free fatty acids (12%), LDL (23%), VLDL (17%), plasma peroxides (25%), and urinary peroxides (55%), while increasing HDL by 18%. Glibenclamide showed moderate improvement in glycemic control, but only had a significant effect on triglycerides (10%), and peroxides (15% plasma, 19% urine). Neither treatment affected HbAlc levels.

No side effects or contraindications are known with bilberry fruit. High doses and prolonged use of the leaves, however, may lead to chronic intoxication. This manifested in animals as cachexia, anemia, icterus, and excitation. Extremely high doses (1.5 g/kg per day) of the leaves over long periods could result in death.

Fenugreek (Trigonella foenum-graecum)

Fenugreek is one of the oldest medicinal plants. Proposed mechanisms of action include delay of gastric emptying, slowing carbohydrate absorption, inhibition of glucose transport, increased erythrocyte insulin receptors, and modulation of peripheral glucose utilization. In animal and several small human trials, fenugreek seeds have been found to lower fasting serum glucose levels, both acutely and chronically.

In people with type 1 diabetes, ingestion of defatted fenugreek seed resulted in significant improvement in fasting blood sugar levels and glucose tolerance, as well as a 54% reduction in 24-hour urinary glucose excretion, and reductions in LDL, VLDL, and triglycerides, indicating that fenugreek may aid with insulin secretion.

Several small clinical trials have been conducted in type 2 diabetics. In one study, fenugreek-treated patients showed statistically significant mean improvements for glucose-tolerance test scores and serum-clearance rates of glucose. In a series of two crossover studies, significant mean improvements were seen in the fasting blood glucose levels and glucose-tolerance test results in the fenugreek-treated patients, even though the dose of their standard antidiabetic medication (glibenclamide, glipizide, or metformin) was reduced by 20% prior to the study period. The fenugreek patients also reported subjective improvements in polydipsia and polyuria. In a study of newly diagnosed people with type 2 diabetes, however, the benefit of fenugreek seeds was not seen to be significantly different than diet and exercise.

In their review of clinical trials, Yeh and colleagues found that whole raw seeds, extracted seed powder, gum isolate of seeds, and cooked whole seeds seemed to decrease postprandial glucose levels, while degummed seeds and cooked leaves did not.

No adverse effects have been reported in clinical trials of fenugreek, but interactions are possible due to decreased intestinal absorption. Hypoglycemic symptoms are to be expected, and should be monitored.

Garlic and Onion (Allium sativa and Allium cepa)

Onions and garlic have demonstrated blood sugar lowering action in several studies. The active constituents are believed to be the sulfur containing compounds allyl propyl disulfide (APDS) and diallyl disulfide oxide (allicin). APDS may lower glucose levels by competing with insulin for inactivating sites in the liver, resulting in an increase of free insulin.

In clinical trial, onion extracts reduced blood sugar levels in a dose dependent manner. A second small study showed acute decrease in fasting blood glucose and increase in insulin, showing an insulin-mediating effect in nondiabetics. Also in nondiabetics, using garlic was shown to decrease fasting serum glucose. Studies in diabetics, however, have been mixed.

As well as potential hypoglycemic effects, garlic and onions have cardiovascular and immune enhancing qualities, and are generally well tolerated. The use of these herbs in diabetes is valuable. Care is indicated with patients on anticoagulants.

Ginseng Species (Panax ginseng and Panax quinquefolius)

Ginseng root has been used for over 2,000 years for health promotion. Of the ginseng species, American ginseng (P. quinquefolius) and Asian ginseng (P. ginseng) are the most commonly used. Reported mechanisms of action include decreased rate of carbohydrate absorption into the portal hepatic circulation, increased glucose transport, and uptake mediated by nitric oxide, increased glycogen storage, and modulation of insulin secretion.

There are several clinical trials that provide evidence for the hypoglycemic effects of ginseng. One study demonstrated a reduction in the levels of fasting blood glucose and HbAlc in type 2 diabetes when ginseng was taken before meals. The subjects also showed mood elevation, improved psychophysiological performance and physical activity, and reduced body weight.

In a second group of studies on ginseng and people with type 2 diabetes, ground American ginseng root in capsules of varying dosage were administered prior to an oral glucose challenge. Ginseng significantly affected postprandial glycemia, with significant interaction for area under the curve. Compared with placebo, all ginseng doses reduced glycemia, without significant effect as to time of administration. In a second similar study, people without diabetes were compared to those with type 2 diabetes. In nondiabetics, significant reductions in postprandial glucose were found only when the ginseng was taken 40 minutes prior to the challenge. In people with diabetes, however, reductions in glucose were seen regardless of when ginseng was taken, either at challenge or before .

Adverse effects for ginseng have been reported, and include nervousness and excitation. These generally diminish with increased use or dosage reduction. Ginseng may inhibit the effects of warfarin, and interact with the monoamine oxidase inhibitor phenelzine. Massive doses of ginseng may result in “ginseng abuse syndrome,” characterized by hypertension, insomnia, hypertonia, and edema.

Gymnema (Gymnema sylvestre, Gumar)

Gymnema, an Ayurvedic herb, has been used for centuries as a treatment for diabetes. Gumar, the Hindi name, literally means “destroyer of sugar.” Mechanism of action is unknown, but postulations include an increase in glucose uptake and utilization, increase in insulin release through cell permeability, increase in beta-cell number, and stimulation of beta-cell function.

Chewing gymnema blocks the sensation of sweetness. Individuals who had gymnema extracts applied to their tongues prior to meals ate fewer calories compared to controls. This has not been shown with ingestion of capsules or tablets, however.

In people with type 1 diabetes, supplementation with gymnema resulted in insulin requirements being decreased by one half, and reduced average blood glucose levels. HbAlc levels were reduced, but still remained higher than normal. Cholesterol and triglycerides were lowered significantly. Gymnema appears to enhance the action of insulin in type 1 diabetes.

In a study of 22 people with type 2 diabetes, gymnema taken along with their oral hypoglycemic drugs improved glucose control in all 22 participants. Further, 21 of the 22 were able to reduce their oral hypoglycemic medication dose considerably, and five were able to discontinue medication altogether and maintain glycemic control with gymnema alone.

Gymnema extract given to healthy volunteers does not produce any blood sugar lowering or hypoglycemic effects. No side effects have been noted.

Soy (Phytoestrogens)

Phytoestrogens in general, and soy in particular, have been receiving increased attention of late due to substantial data that consumption of plant-based phytoestrogens have a beneficial impact on health. In diabetes, soy is thought to be beneficial both for glycemic control and for obesity, although the mechanism of action remains unclear.

In a recent study of postmenopausal women with diet-controlled type 2 diabetes, phytoestrogen supplementation resulted in significantly lower mean values for fasting insulin, insulin resistance, HbAlc, total cholesterol, LDL, cholesterol/HDL ratio, and free thyroxine. These results show that dietary supplementation with soy phytoestrogens favorably alter insulin resistance, glycemic control, and serum lipoproteins. A study examining a soybean-derived Touchi extract was tested against placebo in people with borderline type 2 diabetes. Initial fasting glucose and HbAlc gradually decreased, reaching statistical significance after 3 months. There were no complaints of side effects or abdominal distention.

A review of the literature on soy and diabetes revealed that soy protein, along with soy fiber, decreased LDL, VLDL, total cholesterol, and triglycerides; decreased postprandial hyperglycemia with no effect on serum insulin; and improved glucose tolerance and glycated hemoglobin. While the number of studies is small, the results are promising.

TABLE. Interactions and Contraindications of Selected Herbs

Herb	Contraindications	Interactions
Bitter melon (Momordica charantia)	Pregnancy	Insulin, chlorpropamide
Bilberry (Vaccinium myrtillus)	None known	Warfarin and antiplatelet drugs
Fenugreek (Trigonella foenum-graecum)	Pregnancy	Insulin, cholesterol lowering drugs, may retard absorption of oral drugs, may interfere with warfarin
Garlic and onion (Allium sativa and Allium cepa)	Stomach inflammation, pregnancy, low thyroid, presurgery, acid reflux	Insulin, warfarin, indomethacin, dypiridamole, anticoagulants, may be protective against acetaminophen and isoprenaline toxicity
Ginseng species (Panax ginseng and P. quinquefolius)	Hypertension, acute asthma, acute infection, excessive menstruation, nosebleeds	Insulin, warfarin, caffeine, phenelzine, lithium, amitriptyline, potentiates amoxicillin and clavulanic acid, morphine, methamphetamine
Gymnema (Gymnema sylvestre, Gumar)	None known	Insulin, enhances glybenclamide and tolbutamide
Soy (Phytoestrogens)	Nontoxic goiter	Thyroxine in infants, estrogen replacement therapy

Drug-Herb Interactions

While generally well tolerated, many botanical substances react with other medications. Table presents the contraindications and interactions of the botanicals discussed.

Less Well-Studied Beneficial Herbs

Table Less Well-Studied Botanicals that May Benefit Diabetes

provides botanical species that are not as well studied for their effects on diabetes, but have shown potential in at least one study.

Conclusion

A plethora of botanical substances exist that affect diabetes. Many of the lesser known herbs presented are from the Ayurvedic or Chinese medical systems, and have been used successfully in other countries with good results, but without the benefit of the rigorous scientific study required in the United States. As the world becomes smaller, more of these traditional medicines may become available.