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Biological Complementary Therapies: a Focus on Botanical Products in Diabetes

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Biological Complementary Therapies: a Focus on Botanical Products in Diabetes In Brief to Practice Research From / Complementary & Integrative Medicine Several botanical and biological products claim to lower blood glucose or decrease complications of diabetes, and some of these are being used by peo- ple with diabetes. Products thought to lower blood glucose include gymnema, fenugreek, bitter melon, ginseng, and nopal. Claims have also been made for aloe, bilberry, and milk thistle, but there is less evidence in support of these. Botanical products thought to decrease diabetes complications include ␥- linolenic acid, ginkgo biloba, and garlic. A vitamin-like substance, ␣-lipoic acid, has been used to treat neuropathic complications. Biological Complementary Therapies: A Focus on Botanical Products in Diabetes No one has thoroughly determined concerns about possible side effects3 how many patients with diabetes use and drug interactions.4 Patients using complementary therapies. A recent complementary therapies have experi- Laura Shane-McWhorter, PharmD, survey of diabetes educators in the enced many serious side effects; in BCPS, FASCP, CDE, BC-ADM western half of the United States1 eval- some cases, they may attribute these uated the most frequently recom- effects to another medication. Because mended and used alternative thera- patients often take medications to pies. These included physical activity, treat their diabetes, concomitant use self-help groups, lifestyle diets, laugh- of complementary therapies may also ter and humor, relaxation therapy, result in toxicity secondary to exag- prayer, imagery/visualization, medita- gerated effects or sub-therapeutic tion, massage, and music therapy. effects of their conventional medica- Although botanical products were tions. included in the survey, they were not Another concern relates to the vari- frequently recommended or used. ability of products. Botanical products Another survey of alternative treat- are available in capsules and tablets, ments used by patients with diabetes2 as well as in other forms, such as did indicate that herbal treatments are water extracts (also called decoctions used along with other modalities. In or infusions), tinctures (hydroalco- some cases, patients used these treat- holic extracts), and glycerites (glyc- ments instead of conventional medica- erin-extracted preparations that are tions, and severe complications, alcohol-free). All vary in potency. In including increased hospitalizations, addition, product quality may depend ketoacidosis, and acute hyperglycemia, on what part of the plant was used, occurred. how it was stored, how long it was Technically, an herbal product is stored, the processing technique, and made from the leaves and roots of a how the extract was prepared.3 plant, whereas a botanical product Some products are available in a includes parts or pieces from the form standardized for pharmacologi- whole plant. However, these terms are cal activity. This should guarantee often used interchangeably in discus- that there is consistency from batch to sions of complementary therapies. batch and that the active ingredients are stable.5 However, standardization CONCERNS ABOUT BIOLOGICAL is not simple because, for many OR BOTANICAL THERAPIES botanicals, the active constituents are unknown. A product may be stan- As with conventional medicines, the dardized for one or more biologically use of complementary therapies raises active compounds, but that com- 199 Diabetes Spectrum Volume 14, Number 4, 2001 pound may not be the active ingredi- tions may occur from the additive along with other legumes.9,10 The ent. Pharmacological action may effects when used concomitantly with plant grows in India, Egypt, and the come from the additive or synergistic hypoglycemic agents. Middle East.9 effects of several ingredients, none of Clinical studies. There are only a Fenugreek has also been used as a which separately has the same activity few human studies, and these do not medicinal agent to treat diabetes, con- as the whole plant.6 Furthermore, report important design details, such stipation, and hyperlipidemia.10 It has active constituents in extracts or dried as blinding or randomization. been used topically to treat inflamma- botanicals may vary secondary to geo- One study14 was conducted in type tion, and it has been used postpartum graphical or soil differences, differ- 1 diabetic patients on insulin, 27 of with a substance called jaggery to pro- ences in exposure to sunlight or rain- whom took 200-mg gymnema cap- mote lactation. Because its taste and fall, differences in the time of harvest, sules after breakfast and supper and odor resemble maple syrup, it has and differences in the methods of dry- 37 of whom took insulin only for a been used to mask the taste of medi- ing, storing, and processing. All of period of 6–30 months. After 6–8 cines.9 these variables may affect pharmaco- months, mean HbA1c decreased in the Chemical constituents of the plant logical activity.7 gymnema group from a baseline of include saponins, many of which are Other factors involve potential 12.8 to 9.5% (P < 0.001). After glycosides of diosgenin.9 The seeds misidentification, mislabeling, and 16–18 months, 22 patients remaining also contain the alkaloids trigonelline, possible addition of unnatural toxic on gymnema had a mean HbA1c of gentianine, and carpaine compounds. substances, such as adulteration with 9% (P values not given). At the end of Other components of the seeds heavy metals or steroids and contami- 26–30 months, six patients remaining include several C-glycosides. The nation with microbes, pesticides, on gymnema had a mean HbA1c of seeds contain up to 50% mucilagi- fumigants, and radioactive products.7 8.2% (P values not given). nous fiber.9 Other seed constituents Mean fasting blood glucose (FBG) include 4-hydroxyisoleucine, an BOTANICAL PRODUCTS THAT also decreased from a baseline of 232 amino acid, and fenugreekine. MAY LOWER BLOOD GLUCOSE to 177 mg/dl after 6–8 months 150 Proposed mechanism of action. LEVELS mg/dl after 16–18 months, and 152 Fenugreek is thought to delay gastric mg/dl after 20–24 months (P values emptying, slow carbohydrate absorp- Gymnema not given). The mean insulin dose tion, and inhibit glucose transport.16 It A member of the milkweed family, decreased from a baseline of 60 to 45 has been shown to increase erythro- gymnema (Gymnema sylvestra) is a units/day after 6–8 months and to 30 cyte insulin receptors and improve woody plant found in tropical forests units/day at 26–30 months (P values peripheral glucose utilization, thus of India and Africa.8–10 For more than not given). Patients on placebo had no showing potential pancreatic as well 2,000 years, people have chewed its significant changes from baseline. as extrapancreatic effects.17 leaves to treat “madhu meha” (“honey Another study15 was conducted in Various components of the seeds urine”).9 Used in Ayurvedic medicine, patients with type 2 diabetes on sul- have varying activities. For example, it is thought to destroy a person’s abil- fonylureas; 22 took 400 mg/day of the component called fenugreekine, a ity to discriminate sweet taste; hence, gymnema capsules in addition to sul- steroidal sapogenin peptide ester, may it is often called “gurmar” or “sugar fonylurea treatment, and 25 took a have hypoglycemic properties.10 destroyer.”8 placebo and sulfonylureas for a peri- Trigonelline, another component, may Chemical constituents of the plant od of 18–20 months. Mean HbA1c exert hypoglycemic effects in healthy include the gymnemic acids (gym- decreased from a baseline of 11.9 to patients without diabetes,10 but other nemosides), saponins, stigmasterol, 8.48% (P < 0.001). Mean FBG studies have shown that fenugreek has quercitol, and the amino acid deriva- decreased from 174 to 124 mg/dl no effect on fasting or postprandial tives betaine, choline, and trimethy- after 18–20 months (P < 0.001). Five blood glucose levels in nondiabetic lamine.8 Gymnema has been used for patients were able to discontinue sul- subjects.18 centuries to treat diabetes.10 fonylureas. In this study, lipids also Side effects and drug interactions. Proposed mechanism of action. decreased significantly. Patients on The main side effects are flatulence and Although the exact mechanism is placebo had no significant changes in diarrhea, which subside after a few unknown, there are a variety of theo- HbA1c, FBG, or lipids. days. However, fenugreek also has rized mechanisms. Besides impairing Clinical notes. Because of the pos- uterotonic properties.10 Hypersensitivity the ability to discriminate sweet taste, sibility of hypoglycemia when gymne- reactions have also been reported,10 gymnema increases the enzyme activi- ma is used with insulin or other dia- including rhinorrhea, wheezing, and ty responsible for glucose uptake and betes agents, doses for existing dia- fainting after inhalation of the fenu- utilization.11 It may stimulate ␤-cell betes therapies may have to be adjust- greek-seed powder. Wheezing and function, increase ␤-cell number, ed with the addition of gymnema. facial angioedema after application of a and/or increase insulin release by This product should not be used with- topical fenugreek paste for dandruff increasing cell permeability to out medical supervision. A typical was reported in a patient with chronic insulin.8,12 In pancreatectomized ani- dose is 400 mg/day standardized to asthma.19 mals, it has no hypoglycemic effect, contain 24% gymnemic acids.8,10 Because fenugreek is a member of indicating that its effect may require the Leguminosae family, which in- some residual ␤-cell function.13 Fenugreek cludes peanuts,9 it is theoretically pos- Side effects and drug interactions. Fenugreek (Trigonella foenum-grae- sible for someone with a peanut allergy No side effects have been reported sec- cum) has been used as a cooking spice to react to fenugreek. However, this ondary to gymnema use. Hypoglycemia and flavoring agent for centuries.9 It is reaction has never been reported. is a potential side effect;10 drug interac- a member of the Leguminosae family, All of fenugreek’s side effects may 200 Diabetes Spectrum Volume 14, Number 4, 2001 10 occur in infants of nursing mothers Clinical notes.
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