natural products for the management of type 2 diabetes...

www.pharmacytoday.org58 PharmacyToday • August 2014

Objective: To provide pharmacists with practical information to guide consum-ers in their choices of herbal products and dietary supplements for the manage-ment of type 2 diabetes mellitus (T2DM) and its comorbid disease states.

Summary: The herbal and dietary supplement market has grown exponentially over the past decade as Americans increasingly use such agents for generalized health and the prevention and treatment of chronic disease states.1 Pharmacist ad-vice is often requested on the use of these agents for the management of T2DM; however, this is an area that has insufficient evidence to support confident recom-mendations. Many published studies involving herbal agents and dietary supple-ments are small and poorly designed, with heterogeneous results. Pharmacists should be aware of the safety and efficacy data available for these agents, recognize potential drug interactions, and identify acceptable manufactured products.

Conclusion: The strongest scientific evidence for blood glucose lowering effect is associated with alpha-lipoic acid and fenugreek. There is also good evidence supporting the use of ivy gourd, gymnema, and vitamin E for management of hyperglycemia; however, caution should be used when recommending vitamin E. Pharmacists should advise consumers to disclose use of any of these products to all of their health care providers.

Keywords: Diabetes, herbal supplements, dietary supplements, botanicalsPharmacy Today. 2014(August);20(8):58–72.

CPE

Natural products for the management of type 2 diabetes mellitus and comorbid conditionsJennifer Dixon Smith and Valerie B. Clinard

Jennifer Dixon Smith, PharmD, CPP, BC-ADM, CDE, is Associate Professor, Pharmacy Practice, and Valerie B. Clinard, PharmD, is Vice Chair, Experiential Education, and Associate Professor, Pharmacy Practice, Campbell University College of Pharmacy and Health Sciences, Buies Creek, NC.

Development: This home-study CPE activity was developed by the American Pharmacists Association.

Published concurrently in Pharmacy Today and the Journal of the American Pharma-cists Association (available online at www.japha.org).

Learning objectivesAt the conclusion of this knowledge-based activity, the pharmacist will be able to:

■ Identify natural products and dietary supplements associated with an anti-hyperglycemic effect.

■ Describe safety and efficacy data as-sociated with the most commonly used agents for diabetes management.

■ Identify important drug–drug inter-actions associated with the most commonly used agents for diabetes management.

■ List three items that should clearly be identified on the package labeling be-fore recommending a particular herbal or dietary supplement.

The American Pharmacists Association is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education (CPE). The ACPE Universal Activity Number assigned to this activity by the accredited provider is 0202-0000-14-161-H01-P. Disclosures: Jennifer Dixon Smith, PharmD, CPP,

BC-ADM, CDE, has served as a consultant to AstraZeneca and Bristol-Myers Squibb. Valerie B. Clinard, PharmD, and APhA’s editorial staff declare no conflicts of interest or financial interests in any product or service mentioned in this activity, including grants, employment, gifts, stock holdings, and honoraria. For complete staff disclosures, please see the APhA Accreditation Information section at www.pharmacist.com/education.

Accreditation informationProvider: American Pharmacists AssociationTarget audience: PharmacistsRelease date: August 1, 2014Expiration date: August 1, 2017Learning level: 1

ACPE number: 0202-0000-14-161-H01-PCPE credit: 2 hours (0.2 CEUs)Fee: There is no fee associated with this activity for members of the American Phar-macists Association. There is a $15 fee for nonmembers.

www.pharmacist.com August 2014 • PharmacyToday 59

CPE natural products for t2dm and comorbid conditions

Preactivity questionsBefore participating in this activity, test your knowledge by answer-ing the following questions. These questions will also be a part of the CPE assessment.

1. Which dietary supplement has data that demonstrate a possible benefit in A1C reduction in patients with T2DM?a. Chromiumb. Pyridoxinec. Seleniumd. Zinc

2. Which fat-soluble vitamin has evidence suggesting that use of

high doses may increase the risk of death and, thus, should not be recommended for management of T2DM?a. Pyridoxineb. Alpha-tocopherolc. Alpha-lipoic acidd. Zinc

3. Which herbal agent is more likely to increase bleeding risk when

used concomitantly with anticoagulants?a. Bitter melonb. Burdockc. Cinnamond. Fenugreek

IntroductionThe use of herbals and dietary supplements for generalized health and the prevention and treatment of chronic disease states is increasing throughout the United States.1 The most recent National Health and Nutrition Examination Survey (NHANES) data (2003–06) indicates that approximately 53% of Americans aged 20 years and older use dietary supple-ments, representing a 10% increase in use from the 1988–94 data.2,3

Similarly, a secondary analysis of the complementary and alternative medicine (CAM) supplement to the 2002 Na-tional Health Interview Survey (NHIS) found that 57.3% of adult dietary supplement users took such products to treat a specific medical condition in the previous 12 months.4 Ac-cording to a 2008 study, individuals with diabetes are 1.6 times more likely to use alternatives to traditional medicine compared with those without the disease.5

Access to herbal and dietary supplements was greatly enhanced by passage of the Dietary Supplement Health and Education Act of 1994 (DSHEA).6 Prior to DSHEA, dietary supplements were held to the same regulatory requirements as other foods.7 Now, the manufacturer of a dietary supple-ment is responsible for ensuring product safety prior to mar-keting, while FDA is tasked with taking action against un-safe dietary supplements after products reach the market.7

Manufacturers do not require FDA approval to sell di-etary supplements, and the agency does not maintain a list of manufacturers or the dietary supplement products they sell.7 FDA does call for “good manufacturing practices,” but the burden of proof for verifying product safety is left up to the government. Thus, herbals and dietary supplements comprise part of a thriving, unregulated market. Given this

lack of regulation, such products may be contaminated with other substances, may not contain the intended ingredient, or may be ineffective.

Adding to the problems of a growing, unregulated mar-ket is uncertainty about the generalized safety and efficacy of these products. To date, only a few randomized clinical trials of product safety and efficacy have been conducted and published, and the sample size of many of these stud-ies has been too small to draw reliable conclusions. Further, many of the studies on botanical products use different parts of the plant (e.g., root, stem, leaf), making it difficult to draw reliable conclusions about the safety and efficacy of each constituent.8 Given the limited data available, concern exists regarding these products’ adverse effects, contraindications, and appropriate doses.

Thousands of plant-derived herbs have been implicated in the treatment of diabetes,1 and a plethora of natural prod-ucts—mostly in combination—are marketed for lowering blood glucose and treating comorbid conditions associated with diabetes.9 However, while limited data are available on the ability of many of these agents to safely and effectively lower blood glucose levels, health care professionals should not discount the use of such products.

With more available information, it is possible that one or more of these agents may become an element of conven-tional treatment for patients with diabetes. Metformin—now a cornerstone of diabetes prevention and treatment—is an example of how such a transition can occur. Metformin was discovered from use of the medicinal plant Galega officina-lis to treat diabetes.10–12 Based on the recommendation of the World Health Organization Expert Committee on Diabetes, efforts are currently underway to determine the utility of other traditional medicinal herbs in diabetes care.11

However, it is difficult to assess the use of herbal prod-ucts and dietary supplements specifically for diabetes. Many studies report the use of CAM approaches to diabetes care, including dieting, relaxation techniques, herbal treatment, prayer, and homeopathy.13 Available studies indicate that prayer and dietary measures are the primary types of CAM used in patients with diabetes.

In a study by Yeh et al.,10 CAM use in patients with diabe-tes included prayer and spiritual practice (28%), herbal rem-edies (7%), and commercial diets (6%). In a separate study by Bell et al.,14 a greater number of individuals with diabetes were found to use CAM approaches compared with those without the disease (73% vs. 61%); however, a significantly lower number of respondents with diabetes used non-vita-min, non-mineral natural products compared with respon-dents without diabetes (15.7% vs. 19.2%). Those with diabetes who did use CAM mostly did so for non-diabetes conditions.

These findings underscore the need to determine the ac-tual use of herbal remedies for diabetes care, as well as antic-ipated and actual outcomes. This review focuses on practical information to aid pharmacists in guiding consumers on the use of herbals and dietary supplements for managing type 2 diabetes mellitus (T2DM) and its comorbid disease states.



Herbal products Bitter melon (Momordica charantia)Bitter melon is also known as bitter gourd, karela, or balsam pear.5 It is sometimes referred to as “vegetable insulin” be-cause its extract components share structural similarities with animal insulin.15,16 Purported mechanisms include en-hanced pancreatic insulin secretion and decreased hepatic gluconeogenesis.16

Safety: Based on animal studies, isolated proteins from bitter melon have abortifacient properties; therefore, bitter melon should be used with caution in women of childbear-ing age.5,16 Bitter melon should be avoided in nursing women, children, and those with allergies to foods in the gourd or melon family.5 Additionally, ingestion of bitter melon seeds may cause favism—the onset of hemolytic anemia—in those with glucose-6-phosphate dehydrogenase (G6PDH) deficien-cy.5

Known drug interactions: Bitter melon may be a p-glyco-protein inhibitor; concomitant use with digoxin should be avoided.16

Efficacy: Bitter melon has shown hypoglycemic effects in various animal models,12 some low-quality human trials, and one case report.16 A randomized controlled trial by Dans et al.17 compared bitter melon extract (1000 mg three times daily) with placebo in patients with uncontrolled T2DM (glycosylated hemoglobin [A1C] levels of 7%–9%). The mean difference in treatment for A1C was 0.22% in favor of bitter melon (non-significant); however, the study sample size was only 40 participants and power was not met.

Fuangchan et al.18 published a study comparing dried bit-ter melon fruit powder doses of 500 mg/day, 1000 mg/day, and 2000 mg/day with metformin 1000 mg/day. The four-week study based efficacy on lowered fructosamine levels, a measure of glycemic control over the past 2–3 weeks. Of the bitter melon doses, only the 2000 mg/day dose showed significant reduction in mean fructosamine levels, but there was no effect on fasting or postprandial blood glucose levels. Bitter melon reduction in fructosamine levels was less than that seen with a suboptimal metformin dose.

Bitter melon in doses of 2 grams per day may have an effect on long-term blood glucose lowering, but immediate effects have not been observed.

Burdock (Arctium lappa)Burdock, which is rooted in traditional Chinese medicine, has been examined for uses as an anti-inflammatory, anti-cancer, antidiabetes, antimicrobial, and antiviral agent.19 Bur-dock root and fruit have been suggested as the parts of the plant that likely contribute the most to producing hypoglyce-mic effects.19 The root contains sitosterol-beta-D-glucopyran-oside, which is thought to have alpha-glucosidase inhibitor activity, and inulin, which helps to regulate blood glucose levels.19 Total lignin from the burdock fruit has suggested an-tidiabetic activity in animal studies.19

Safety: Different parts of the burdock plant contain vary-ing levels of pectin complex. Avoid use in individuals with allergy or intolerance to pectin.16 Burdock should also be

avoided in patients with allergies to ragweed, chrysanthe-mums, marigolds, or daisies. Animal studies suggest in-creased bleeding risk with burdock use; therefore, recom-mend caution with concomitant use of anticoagulants or antiplatelet agents.16 Of greatest concern is that burdock can be confused with belladonna alkaloids during harvesting, and atropine-like effects have been seen following the con-sumption of contaminated burdock.16 Burdock itself does not have atropine-like effects.

Known drug interactions: Burdock tinctures may contain high concentrations of alcohol, which may induce vomiting if combined with disulfiram or metronidazole.16

Efficacy: Animal data and weak human data suggest the root or fruit of burdock may produce hypoglycemic effects, but reliable data is lacking.16 Further studies are needed be-fore recommending burdock for the management of T2DM.

Cinnamon (Cinnamomum cassia)Cinnamon, also sometimes referred to as Chinese cinna-mon,20 is derived from the dried inner bark of evergreen trees grown in the tropical climates of Asia.5,21 The active ingredients in cinnamon include cinnamaldehyde and pro-cyanidin type-A polymers.5,21 It is purported that these con-stituents enhance insulin sensitivity by improving glucose uptake and glycogen synthesis.21

Safety: When used in natural food sources, cinnamon ap-pears to be safe. In clinical trials, gastrointestinal disorders were the most reported adverse effect associated with cin-namon use.16 It should be noted that cinnamon is a top food allergen, so caution should be exercised when recommend-ing its use among mass populations.

Known drug interactions: Cinnamon contains a coumarin component, so caution should be used when recommending with concurrent administration of anticoagulants.5

Efficacy: Results of randomized trials from human and animal studies have indicated hypoglycemic effects; how-ever, the results have been conflicting.16 To date, studies of patients with T2DM have involved the administration of 1, 3, or 6 grams per day of cinnamon in divided doses.22

While there is currently insufficient data to recommend cinnamon for any human condition, its use in the treatment of T2DM seems to be the most desired field of research.16 The use of cinnamon increased substantially after 2003 when Khan et al.23 demonstrated a lowering of blood glucose val-ues in patients with T2DM. Consequently, patients began questioning if cinnamon may be an appropriate alternative

Case study 1A 28-year-old obese female with T2DM requests an herbal supplement to use in addition to metformin for glycemic control. She has no other disease states but is allergic to grass, trees, and ragweed. Name two herbal supplements you would avoid recommending in this patient for glycemic control.

Bitter melon should be avoided in all women of childbearing age because of the risk of miscarriage. Additionally, burdock should not be recommended at this time to any patient for glycemic control given the risk of contamination with belladonna alkaloids. Burdock should also be avoided in patients allergic to ragweed, chrysanthe-mums, marigolds, daisies, or pectin.



or supplement for diabetes management. Allen et al.22 conducted a systematic review and meta-

analysis of randomized trials evaluating cinnamon (mono-preparation or in combination) in patients with T2DM. A total of 10 studies involving 543 participants met eligibility criteria. Doses of aqueous cinnamon extract or raw cinna-mon powder ranged from 120 mg/day to 6 g/day over a pe-riod of 4–18 weeks. Cinnamon was associated with a statisti-cally significant reduction in fasting plasma glucose levels of 24.59 mg/dL. High degrees of heterogeneity were present for A1C levels, but no statistically significant effect was seen in A1C levels (−0.16%).

Leach and Kumar24 conducted a Cochrane Review analysis of randomized controlled trials using cin-namon as monotherapy for type 1 diabetes (T1DM) or T2DM. A total of 10 studies met eligibility criteria (n = 577 participants), with only 2 of the studies dif-ferent from those evaluated in the Allen review. Cin-namon cassia was the predominant form of cinnamon used (mean dose of 2 g/d) for a period of 4–16 weeks. In the meta-analysis, no conclusions could be made re-garding the efficacy of cinnamon on fasting blood glu-cose levels. Of the six trials reporting A1C levels (n = 405), there was no statistically significant difference in A1C levels (mean difference −0.06%).

Further studies are needed before recommending cinna-mon as an agent for glycemic control.

Dandelion (Taraxacum officinale)Dandelion is a member of the Asteraceae family.16 Found growing wild in meadows and pastures of temperate zones, it provides fiber, potassium, iron, calcium, magne-sium, phosphorus, thiamine, and riboflavin when ingested. Dandelion has traditionally been used to treat gastrointes-tinal disorders. FDA has approved dandelion fluid extract and solid dandelion root extract as food additives; they are currently used as salad ingredients and coffee substitutes.

Safety: Dandelion is considered likely safe when taken orally in amounts found naturally in foods,16 earning FDA’s “generally recognized as safe” designation. It has been well-tolerated in human studies, with the most common-ly reported adverse effects being dermatologic in nature, following direct contact. However, safety data beyond 4 months of use is lacking. Use should be avoided in indi-viduals who are allergic to dandelion, honey, chamomile, chrysanthemums, or any member of the Asteracae family.

A theoretical concern is that dandelion stimulates bile secretion and therefore should not be used in individuals with liver or gallbladder disease; however, supporting data for this is lacking. The prudent approach at this time would be to avoid recommending dandelion if liver or gallbladder disease is present.

Known drug interactions: Dandelion may cause increased gastric acid secretion; therefore, it may reduce the effec-tiveness of antacids.16 Dandelion may also increase the risk of bleeding, so caution is recommended with concomitant use of anticoagulants or antiplatelet agents.

Efficacy: Animal studies have suggested hypoglycemic effects of dandelion, but no human data is available. One published case report suspected that dandelion induced hypoglycemia when it was added to a neutral protamine Hagedorn (NPH) insulin regimen.25 Dandelion may be considered safe when recommended as part of a natural diet. However, given the lack of human data, dandelion should not be recommended as a hypoglycemic agent at this time.

Fenugreek (Trigonella foenum-graecum)Fenugreek is a fiber-rich plant that is a member of the Faba-ceae family.5,15,16 It is commonly used for glycemic control in foreign countries such as Saudi Arabia and Canada.16 The mechanism of action is thought to be a delay in gastric emp-tying, slowed carbohydrate absorption, and increased insu-lin sensitivity of the tissues.8,15 Fenugreek seeds reportedly increase glucose-dependent insulin secretion.12

Safety: The most commonly reported adverse effects of fenugreek are gastrointestinal,5 including dyspepsia and abdominal distention.26 Fenugreek also has a blood thinning effect5 and may cause hypokalemia.16 Fenugreek should not be recommended for use in individuals aller-gic to members of the Fabaceae family (peanuts, chickpeas, soybeans, or green peas).5,16

Known drug interactions: Because it is rich in fiber, fenu-greek may interfere with the absorption of some oral medi-cations. Therefore, it is recommended that the coadminis-tration of oral medications and fenugreek be spaced out by at least 2 hours.9 Additionally, caution should be exercised with concomitant use of potassium-depleting agents.16

Efficacy: Daily doses of 5–100 grams of fenugreek seed powder have been shown to improve fasting blood glu-cose, postprandial glucose, and A1C levels in patients with T2DM.26

From a pooled analysis, Suksomboon et al.21 determined that fenugreek had a statistically significant decrease in A1C (1.13%), but no effect on fasting blood glucose.

Neelakatan et al.26 conducted a meta-analysis to assess the effect of fenugreek on glucose homeostasis; 10 trials met inclusion criteria, but only 8 were selective for patients with T2DM. Results of the meta-analysis included significant reductions in fasting blood glucose (−0.96 mmol/L), 2-hour blood glucose (−2.19 mmol/L; 7 trials), and A1C levels (−0.85%; 3 trials). Significant reductions in glycemic mark-ers were only found with medium to high doses of fenu-greek seed powder (≥5 g/d).

Fenugreek seed powder in daily doses of at least 5 grams appears to be a safe and effective option for glycemic control in persons with T2DM.

Ginseng—Korean red (Panax ginseng) and American (Panax quinquefolius)While several species of ginseng are used in herbal prod-ucts, the most common are of the Panax genus.27 Other species of ginseng from different botanical families (e.g., Siberian) are sometimes sold as less expensive alternatives.



However, they lack the efficacy data associated with the Panax genus.16

The glucose lowering effect of Panax is attributed to its ginsenosides, but the peptidoglycan and glycan constitu-ents have also shown beneficial effects.1 However, there is great difficulty in standardizing Panax ginseng products. Currently, there are more than 30 identified ginsenosides, so there may be considerable variability in the composition of marketed ginseng products.1

Safety: Insomnia is the most commonly reported side effect. Anxiety, headache, and tachycardia have also been reported.5

Known drug interactions: Caution should be exercised with concomitant use of agents that increase bleeding.16 Ginseng has also been linked to a plethora of potential drug interactions (e.g., antihypertensives, antidepressants, pain relievers, antibiotics); however, data is lacking to definitive-ly support these interactions.16

Efficacy: Vuksan et al.1 evaluated the acute and chronic effects of American and Korean red ginsengs using a stan-dardized ginsenoside component administered at specific times. The study found that doses of 1–9 grams of Ameri-can ginseng were equally effective in the acute and long-term reduction of postprandial hyperglycemia (~15–20%). Chronic antihyperglycemic efficacy of American ginseng was evaluated using 1 gram of ginseng extract 40 minutes before each meal (3 g/d). Similarly, the administration of 2 grams of Korean red ginseng rootlets 40 minutes before each meal (6 g/d) demonstrated acute and chronic anti-hyperglycemic efficacy. Administration time of at least 40 minutes prior to the meal was significant.

A separate study evaluating the safety and efficacy of Korean red ginseng observed acute efficacy for glycemic control, but did not see any long-term effects as measured by A1C levels.28

High variability in the composition of ginseng products is linked to the inconsistent efficacy observed in studies, with no standardization existing at this time for the differ-ent ginsenosides and their ratios.1 Limited efficacy data and lack of standardization limit the recommendation of Panax ginseng products for glycemic control.

Gymnema (Gymnema sylvestre)Gymnema is a woody, climbing plant native to the tropi-cal forests of central and southern India.8 In Hindu folk-lore, chewing gymnema leaves results in the inability to taste sweets. It is therefore also known as “gurmar,” which means “destroyer of sugar” in Hindi.8 The exact mechanism of action is unknown, but suggested mechanisms include enhanced insulin secretion, beta cell regeneration, and en-hanced peripheral glucose utilization.8

Safety: Based on limited trial data, gymnema appears to be safe, with the most notable side effect being taste al-teration.8 Patients may experience diminished perception of sweet taste and enhanced perception of bitter taste.

Known drug interactions: Gymnema may enhance the lipid-lowering effects of antilipemic agents and the weight loss effects of antiobesity agents.16

Efficacy: Animal studies have demonstrated glucose-lowering effects in animals with residual pancreatic func-tion, but not in pancreatectomized animals; however, gymnema has demonstrated efficacy in human trials in both patients with T1DM and T2DM.8

Baskaran et al.29 conducted a non-randomized study of 47 patients with T2DM. For 18–20 months, 22 of the pa-tients were administered 400 mg/day of GS4, an extract from gymnema sylvestre leaves, in combination with oral hypoglycemic agents. Statistically significant reductions in fasting blood glucose values (−2.78 mmol/L) and A1C lev-els (-3.43%) were reported. Almost all patients in the treat-ment group required dose reduction or discontinuation of sulfonylureas within several weeks (unspecified time). The study authors also observed elevations in serum insulin levels in the fasting and postprandial state in those partici-pants treated with GS4.

It may be safe to recommend gymnema for glycemic lowering in T2M. However, further well-controlled trials need to be conducted in this population to establish safety and efficacy.

Ivy gourd (Coccinia indica)Ivy gourd is an aggressive climbing vine found in tropical areas.16 Both human and animal studies have found that the fruit and leaves of ivy gourd can lead to reductions in fasting and postprandial blood glucose values. Ivy gourd is a source of fiber, which may account for its ability to lower blood glucose levels, but it is also speculated to pos-sess insulin-like effects.12,16 Ivy gourd’s exact mechanism of action remains unclear.8

Safety: Published clinical trials report a lack of adverse events associated with the use of ivy gourd.16 In a 2008 study using an alcoholic extract of ivy gourd, participants experienced mild disturbance of the gastrointestinal tract (abdominal distention, flatulence, constipation, and gas-tritis). However, more participants in the placebo group experienced these symptoms than those in the interven-tion group, and the symptoms resolved within 1 week.30

Known drug interactions: No known drug interactions exist.16

Efficacy: Evidence for the potential efficacy of ivy gourd in lowering blood glucose dates back to a 1979 study con-ducted in Bangladesh, which found that 1800 mg/day of ivy gourd decreased both fasting and postprandial blood glucose values, with no reported side effects.8,31 A case se-ries published by Kamble et al.32 compared use of 6 g/day of ivy gourd to that of chlorpropamide and found that the two treatments were similar in their ability to lower fast-ing and postprandial blood glucose levels.

Additional data are needed prior to recommending ivy gourd for treatment of T2DM.

Nopal (Opuntia streptacantha)Prickly pear cactus, known as nopal to the Mexican com-munity, has high soluble fiber and pectin content in its fresh state,15 which may affect intestinal glucose uptake.8

Safety: Diarrhea and increased stool volume have been



reported with nopal use,5 as have allergic nasal inflamma-tion and asthma.16 Nopal is likely safe when used as a food source.16

Known drug interactions: Nopal may increase bleeding when combined with anticoagulants or antiplatelet agents.16 Additionally, nopal may cause increased drug levels of agents metabolized through the cytochrome P450 enzyme system. Nopal may also help reduce cholesterol; thus an additive effect is possible when combined with cholesterol-lowering agents.

Efficacy: The leaves and stem of nopal have been studied for glycemic effects, with nopal shown to decrease glucose in both pancreatectomized and nonpancreatectomized ani-mals.8 Additionally, doses of 100–600 grams/day have pro-vided hypoglycemic effects in individuals with T2DM.15

Studies are generally limited on this readily available plant. However, given the lack of significant side effects seen in trials and the possible glucose-lowering effect of nopal, it can safely be recommended for consumption as a food source.

Onion (Allium cepum)Onion is part of the Allium species and contains allyl pro-pyl disulphide.8 It is suggested that onion’s hypoglycemic properties are attributable to enhanced pancreatic insulin secretion and/or improved hepatic storage of glycogen.

Safety: Onion is likely safe when consumed as part of a normal diet,16 though increased dietary intake may induce heartburn or dyspepsia. Onion has resulted in lowered blood pressure in patients both with and without hyperten-sion; therefore, its increased intake should be accompanied by cautious monitoring of blood pressure.

Known drug interactions: P-glycoprotein substrates and medications metabolized by the cytochrome P450 enzyme system may interact with onion.16 Additionally, onion may increase bleeding risk when combined with anticoagulants or antiplatelet therapy.

Efficacy: Onion has reduced fasting and postprandial blood glucose levels in both animal (rabbit) and human studies.12 Given as a single orally administered dose of 25, 50, 100, or 200 grams of aqueous onion extract (either boiled or raw), onion lowered fasting blood glucose levels in a dose-dependent manner and was comparable to tolbutamide—a first-generation secretagogue. Additionally, an onion diet of 3 x 20 grams of fresh onion decreased or maintained blood glucose levels in study participants with T2DM.12

Onion is considered safe when consumed as part of a normal healthy diet. Therefore, pharmacists may safely rec-ommend increased dietary intake for patients who do not take anticoagulants and are not currently being treated for dyspepsia or heartburn.

Psyllium (Plantago ispaghula)Fiber intake for the general population is recommended as 14 g/1000 kcal, which for most individuals translates into 25–35 grams of fiber per day.33,34 The fiber consumption recommen-dation for individuals with diabetes is the same as that for the general population.33 Psyllium is a soluble fiber; its seed

husk and leaves have been studied for potential blood glu-cose lowering effects.16 While the exact mechanism of glu-cose lowering remains unclear,16 it has been suggested that psyllium may enhance insulin action or insulin-independent effects.35

Safety: Adequate amounts of water should be consumed with psyllium-containing products to prevent swelling and blockage of the throat and intestines.16 Health care workers with repeated exposure to psyllium may be at increased risk for development of an allergy to the fiber.

Known drug interactions: Psyllium may reduce the absorp-tion of some oral agents. Oral medications should be taken 1 hour before or 2 hours after psyllium.

Efficacy: According to the American Diabetes Association (ADA), fiber has lowered postprandial blood glucose levels modestly in available trials.33 Other sources have associated psyllium with lower mean daily glucose levels, lower post-prandial blood glucose concentrations, and lower A1C lev-els.34

Anderson et al.36 conducted a study to assess the safety and efficacy of psyllium in male patients with T2DM. For 8 weeks, participants ingested 5.2 grams of psyllium seed husk twice daily (20–30 minutes before morning and eve-ning meals). All-day blood glucose levels were significantly lower in the psyllium group compared with the placebo group (−11%). As in previously published studies, Anderson et al. observed a “second meal effect” in the psyllium-treated group, with psyllium doses taken before morning meals re-sulting in statistically significant lower post-lunch postpran-dial blood glucose levels compared with the placebo group (−19.2%).

Ziai et al.37 evaluated the glycemic benefit of psyllium in persons with T2DM in a double-blind, placebo-controlled study. Psyllium dosing, dosing schedule, and study dura-tion were identical to the study conducted by Anderson et al. Of the 49 enrolled patients, 36 completed the study, with no attrition in the treatment group due to adverse effects. A statistically significant decrease in A1C levels from baseline were reported in the psyllium-treated group [10.5% (±0.73) to 8.9% (±0.23)], while an increase was seen in the placebo-treated group [9.1% (±0.51) to 10.5% (±0.59)].

When either added to one’s regularly consumed diet or used as fiber supplementation, psyllium may help benefit glycemic control.

Dietary supplements Alpha-lipoic acidAlpha-lipoic acid (ALA) is an endogenous dithiol antioxidant that is naturally synthesized in the body.16 ALA acts as an an-tioxidant and coenzyme, and evidence exists that it may aid in the treatment of both T2DM and diabetic neuropathy.16,38

Safety: ALA is generally well tolerated when daily doses do not exceed 1200–1800 mg. Common adverse effects in-clude nausea, vomiting, and vertigo, especially at the higher dose ranges (1200 mg or above).16,39,40

Use of ALA is a risk factor for the development of insulin autoimmune syndrome (IAS), also known as Hirata disease, a rare cause of hypoglycemia due to the production of auto-



antibodies to insulin in individuals who have not previously been treated with insulin.16 Additional risk factors for IAS in-clude the use of sulfhydryl drugs (e.g., methimazole, mercap-topropionyl glycine, and glutathione). Risk is also higher in persons from East Asia and certain patients of native North American descent.

Known drug interactions: Significant drug interactions have not been noted with ALA.

Efficacy: ALA administered orally or via IV may improve insulin sensitivity and glucose disposal in persons with T2DM.41–46

Mazloom et al.46 conducted a randomized, placebo-con-trolled study to assess the effect of ALA on A1C and blood glucose levels in 70 patients with T2DM. Patients remained on oral diabetes medications and were randomized to re-ceive 300 mg ALA or placebo three times daily for 8 weeks. Compared with baseline, patients in the ALA group showed significant reductions in mean fasting blood glucose levels and 2-hour postprandial glucose levels. No significant dif-ference between ALA and placebo treatment groups was observed.

A separate randomized, placebo-controlled trial43 as-sessed the effects of ALA on insulin sensitivity in non-insu-lin-dependent diabetes patients. Patients were randomized to 600 mg ALA (once to three times daily) or placebo. Com-pared with baseline, patients administered 600, 1200, or 1800 mg ALA daily demonstrated significantly increased insulin sensitivity of 15%, 14%, and 22%, respectively. However, a sta-tistically significant difference was not observed compared with placebo. Mild hypoglycemic events were reported in a few subjects, and their dose of oral diabetes medications had to be reduced.

Several studies have also confirmed that ALA is an effec-tive treatment of diabetic peripheral neuropathy (DPN).39,40,47–

50 ALA administered orally or intravenously at doses of 600–1200 mg/day may reduce DPN symptoms.39,40,47–49,51 Symptoms such as burning, pain, numbness, and prickling, as well as attributes of nerve conduction, were improved with 3–5 weeks of supplementation.

Han et al.52 performed a meta-analysis of 15 clinical tri-als to assess safety and efficacy of ALA in patients with DPN. For 2–4 weeks, patients were intravenously adminis-tered 300–600 mg ALA daily. Results from nine of the stud-ies showed significantly improved treatment efficacy in the ALA treatment group compared with placebo. Most of the studies lacked information on adverse effects, adverse events, dropouts, and toxicity. Limitations to this review in-cluded the inclusion of studies with poor methodologies and limited information regarding study design.

Ziegler et al.40 conducted a meta-analysis of four trials (ALADIN I, ALADIN III, SYDNEY, and NATHAN II) to eval-uate the safety and efficacy of administering 600 mg ALA over 3 weeks to patients with diabetes and symptomatic polyneuropathy. Changes in total symptom score (TSS) was assessed daily (except weekends). Patients treated with ALA demonstrated a significant relative improvement in TSS of 24.2% compared with placebo.

Three of the four trials included studies showing the ben-

eficial effect of ALA on TSS. While no effect was seen for A1C levels, significant effects in favor of ALA were observed for neuropathy impairment score (17.1%), NIS of the lower limbs (16%), pinprick sensation (OR = 1.57), touch pressure sensa-tion (OR = 1.35), and ankle reflex (OR = 1.69). The rate of ad-verse effects, which included headache and nausea, did not differ between groups. Limitations of the review included the inclusion of select studies and the short duration of treat-ment.

It is also notable that that some studies have found no benefit of ALA in the treatment of DPN.53,54 While ALA may provide benefit to some patients with DPN, additional stud-ies are warranted to assess its effect on insulin sensitivity and glycemic control.

Alpha-tocopherol/vitamin EVitamin E is a fat-soluble vitamin that exhibits antioxidant properties.16

Safety: Evidence suggests that use of high-dose vitamin E supplements may increase the risk of death from all causes; however, human research is inconsistent.16 Caution is war-ranted prior to recommending vitamin E supplementation to patients. Vitamin E should not be used in patients with bleeding disorders or in those taking anticoagulants, and high-dose vitamin E may increase the risk of congenital heart defects.16 Additionally, vitamin E should not be used in patients with Alzheimer disease because of a significantly increased risk of falls and syncope compared with placebo.5

Known drug interactions: Possible drug interactions with vitamin E include cyclosporine, paclitaxel, sucralfate, and mineral oil.16

Efficacy: It has been suggested that vitamin E may aid in the prevention of both T1DM and T2DM.56,57 Vitamin E may also improve glucose disposal in patients with T2DM, nerve conduction in patients with diabetic neuropathy, and kidney function in patients with T1DM.58–59 Paoloisso et al.60 observed improved insulin action in non-insulin-dependent patients with diabetes who were treated with vitamin E (900 mg dl-alpha-tocopheryl acetate/d).

Blum et al.61 performed a meta-analysis of two random-ized trials to evaluate the cardiovascular protection effects of vitamin E supplementation in patients with T2DM and hap-toglobin 2-2 genotype (a cardiovascular disease risk marker in diabetes). Patients were administered 400 IU daily of vita-min E. Endpoints included nonfatal myocardial infarction, stroke, and cardiovascular disease death, in addition to a composite endpoint. A protective effect of vitamin E was sta-tistically significant for all endpoints except stroke. Detailed information about methodology of the trials was not includ-ed in the meta-analysis. Vardi et al.62 confirmed a possible benefit of vitamin E in patients with T2DM and haptoglobin 2-2 genotype.

In a meta-analysis performed by Suksomboom et al.,63 vitamin E supplementation did not improve glycemic con-trol in the overall group of patients with T2DM. However, vitamin E did improve glycemic control in patients with in-adequate glycemic control at baseline (A1C ≥8%) and baseline serum vitamin E levels below normal ranges.



Other data suggest that vitamin E has no effect on serum glucose, A1C, or fructosamine levels.54,64–66 In the HOPE trial, treatment with vitamin E for an average of 4.5 years had no effect on cardiovascular outcomes.67

Some experts believe that vitamin E supplementation in the form of alpha-tocopherol rather than gamma-tocopherol may be a factor in the observable negative effects or lack of effects reported.16 Gamma-tocopherol is believed to have more antioxidant effects compared with alpha-tocopherol.

Caution should be exercised prior to recommending vita-min E to patients because of possible adverse effects and the lack of beneficial data.

ChromiumChromium is an essential element in the metabolism of car-bohydrates, lipids, and proteins.16 Chromium picolinate, the most common synthetic chromium product evaluated in published literature, is thought to be more completely ab-sorbed and have a greater bioavailability than other chro-mium formulations.68,69 Chromium picolinate has been ad-ministered at doses ranging from 200 to 1400 mcg/day for a period of 6 weeks to 6 months. Other doses of varying forms of chromium have also been studied, including chromium chloride, chromium-enriched yeast, and brewer’s yeast.

Safety: Trivalent chromium, typically found in food and supplements, appears to be safe, with very low toxicity.16 Many of the studies assessing the effects of chromium on pa-tients with T2DM reported either no adverse events or such minimal effects as nausea, vomiting, constipation, headache, and vertigo.16,70,71

Chromium is likely safe when used appropriately, al-though shortened QTc intervals have been reported.16

Known drug interactions: Theoretically, chromium may interact with selective serotonin reuptake inhibitors, mono-amine oxidase inhibitors, antiparkinsonian agents, and cen-tral nervous system stimulants.16 Chromium picolinate may affect the central nervous system metabolism of dopamine, serotonin, and norepinephrine. Additionally, administration of H2 blockers may inhibit the absorption of chromium. Ad-ministration of levothyroxine sodium and chromium should be separated by several hours.

Efficacy: Chromium use in patients with T2DM has been associated with beneficial effects on glucose, lipid metabo-lism, and insulin sensitivity.45,68,69,72–74

Balk et al.69 conducted a systematic review of randomized controlled trials evaluating the effect of chromium supple-mentation on glucose metabolism and lipid profile param-eters. A total of 41 studies comprising 431 patients with ei-ther T2DM or glucose intolerance met the eligibility criteria. Overall, chromium supplementation in patients with T2DM proved statistically significant in reducing A1C by 0.6% and fasting glucose by −1.0 mmol/L; however, lipids were not im-proved. None of the included studies reported differences in patients with glucose tolerance.

However, the results of other studies are inconsistent with these findings.70,71,75,76 Althuis et al.77 conducted a systematic review and meta-analysis of 15 randomized controlled trials to determine the effect of chromium on glucose and insulin

responses. There was no association between chromium and glucose or insulin concentration in subjects without diabetes, while data included in the analysis for patients with diabetes were inconclusive. Kleefstra et al.71 reported similar negative results in a study evaluating chromium supplementation in patients with T2DM on oral agents. Many of the studies evaluated were small and lacked defined methodology or in-formation critical to assessing the trial.

Additional research with more defined endpoints and better methodology should be conducted prior to recom-mending chromium for the management of T2DM.

Pyridoxine/vitamin B6

Pyridoxine (Vitamin B6) is required for the synthesis of sero-tonin and norepinephrine, as well as for myelin formation.16 Pyridoxine supplementation has been assessed for improve-ment of glucose metabolism and in the treatment of diabetic neuropathy.

Safety: Pyridoxine is likely safe when used orally in doses within the recommended dietary allowance.16 Doses greater than 200 mg should be avoided, as reversible neuropathy has been reported with high doses.16,78

Known drug interactions: Due to an additive hypertensive effect, pyridoxine should not be used in combination with other antihypertensives or in patients with cardiovascular conditions.16 Patients treated for Parkinson disease should use caution before taking additional pyridoxine, as it may enhance the metabolism of levodopa when levodopa is taken as a single agent.

Efficacy: Pyridoxine may have a role in the treatment of diabetic neuropathy.38,78–80 In combination with thiamine 25 mg daily, pyridoxine 50 mg may reduce the severity of symp-toms in patients with diabetic neuropathy.38,78

Abbas et al.80 assessed the effect of pyridoxine 50 mg and thiamine 25 mg daily in patients with diabetes. A total of 100 control patients received a tablet identical to that provided to the treatment group but containing only 1 mg of pyridoxine and 1 mg of thiamine. Severity of peripheral neuropathy symptoms decreased in 48.9% of patients in the treatment group, compared with 11.4% in the control group. Because patients’ pyridoxine levels were not reported, it is difficult to determine the role of pyridoxine supplementation in the trial. Conflicting evidence for use of pyridoxine in the management of neuropathy in T2DM patients also exists.38,78

Researchers have also evaluated the use of pyridoxine for impaired glucose tolerance in nonpregnant patients with pyridoxine deficiency, with supplementation not found to significantly improve either glucose tolerance or insulin re-sponse to glucose.81 This finding was affirmed by another study in which 7 of 13 included patients had a pyridoxine deficiency.82

At this time, pyridoxine should not be routinely recom-mended for glycemic control or peripheral neuropathy to pa-tients without pyridoxine deficiency. Additional studies are required.

SeleniumSelenium is an essential trace mineral found in soil, water,



and some foods.16 It functions as a cofactor for the antioxi-dant enzymes.

Safety: Selenium should not be used in patients on hemo-dialysis or immunosuppressants, or in patients with hyper-lipidemia, hypothyroidism, or high risk for development of T2DM.16

Known drug interactions: Possible drug interactions with selenium include HMG-CoA reductase inhibitors, barbitu-rates, and erythropoietin.16

Efficacy: Data do not support use of selenium for the treat-ment of T2DM.83–85 Interestingly, both low concentrations of selenium in toenails and high serum levels of selenium have been associated with an increased risk for the development of T2DM.38,83,84 In one secondary analysis, patients who took selenium 200 mcg daily for an average of 7.7 years had a sig-nificantly increased risk for T2DM.83

Selenium should not be recommended for the treatment of T2DM.

ZincZinc is a trace mineral essential for the functioning of cellu-lar processes, including enzymatic processes.16 Patients with diabetes may be zinc deficient.16,86 Evidence exists that zinc may increase glucose transport into cells and thus assist with insulin-induced glucose transport.87

Safety: Zinc is likely safe when consumed at levels com-monly found in food or at levels lower than the tolerable up-per level: 4 mg for infants aged 0–6 months, 5 mg for infants aged 7–12 months, 7 mg for children aged 1–3 years, 12 mg for children aged 4–8 years, 23 mg for children aged 9–13 years, 34 mg for children aged 14–18 years, and 40 mg for adults aged 19 years or older.16

The most common adverse effects of zinc reported to the California Poison Control System include nausea and vom-iting.88 Caution should be used when zinc is administered as a supplement to patients with gastrointestinal disorders, neurological disorders, hematological disorders, renal insuf-ficiency, immunosuppression, and coagulation disorders, and to men at risk for prostate cancer.16

Known drug interactions: Possible drug interactions in-clude fluoroquinolones, tetracyclines, and calcium salts.16

Efficacy: Zinc supplementation in patients with T2DM has been shown to decrease fasting and postprandial blood glu-cose.89

Gupta et al.89 conducted a double-blind randomized trial assessing the efficacy of zinc supplementation in 50 patients,

including healthy controls and those with poorly controlled T2DM and diabetic neuropathy. Each day, participants re-ceived 660 mg of zinc sulfate orally. After 6 weeks of treat-ment, the group receiving zinc plus an oral antidiabetic ex-perienced a significant decrease in fasting blood glucose and preprandial blood glucose compared with before treatment. Significant changes in motor nerve conduction velocity of the median nerve and the common peroneal nerve were also noted. Randomization, power calculations, adverse events, and interactions were not discussed in the study manuscript.

Zinc’s potential benefits cannot be determined based on the available literature. Additional research is required to as-sess its effect on T2DM prior to making any recommenda-tions to patients.

Pharmacist-directed practical advice Some of the most widely used agents in traditional medicine have derived from plant sources, including aspirin, antima-larials, anticancers, and digitalis.12 However, a current lack of scientific and clinical data establishing the safety and effi-cacy of many currently available “natural” products hinders their use for medicinal purposes in the general population.

According to ADA, “there is limited evidence that the use of vitamin, mineral, or herbal supplements is necessary in the management of diabetes.”33 Therefore, ADA does not provide specific recommendations on the use of herbals and dietary supplements for glycemic control.

Of the natural products and dietary supplements dis-cussed, alpha-lipoic acid and fenugreek demonstrate the strongest scientific evidence for lowering blood glucose lev-els. Additionally, good scientific evidence exists for use of gymnema, vitamin E, and ivy gourd.16

Table 1 provides a summary and pocket guide for natural products commonly used in the management of T2DM. Pa-tients should be aware that these products may contain con-taminants or inappropriate amounts of active ingredients, as they are not required to undergo the same approval process required for medications in the United States.

Common dietary food sources designated by FDA as “generally recognized as safe” (e.g., cinnamon, dandelion, and onion) can be safely recommended for use in the gen-eral diet, with the potential benefit of lowering glucose with minimal adverse effects.

While some assume that consumers use complementa-ry and alternative medicine because of their dissatisfaction with conventional treatment options, a 2004 U.S. study sug-gests otherwise.15 Study participants said they were more concerned with the inability of health care providers to un-derstand the use of such products in the medical manage-ment of disease states than they were about providers’ poten-tial disapproval. This finding underscores the importance of pharmacists being knowledgeable about the available litera-ture on safety and efficacy of herbal and dietary supplement products, as well as the interaction of these products with other pharmacologic treatments.

Before recommending herbal or dietary supplementation for patients with diabetes, consideration should be given to

Case study 2A 74-year-old male patient with T2DM and benign prostatic hyperplasia (BPH) is currently taking selenium. He heard that selenium may be helpful in controlling his BPH as well as his diabetes. His diabetes is well controlled with his current regimen, which includes metformin. He would like to stop taking his metformin and just continue the selenium. He asks you for your opinion.

Selenium is an essential trace mineral that functions as a cofactor for the antioxidant enzymes. Data do not support the use of selenium for the treatment of T2DM, and it has been implicated as a possible risk factor for the development of T2DM.



Table 1. Pocket guide for commonly used natural products in the management of type 2 diabetes mellitus5,16

Supplement Natural Standard evidence grade for

T2DMa

Bottom line/counseling points Commonly studied doses

Alpha-lipoic acid A Alpha-lipoic acid is generally well tolerated when doses do not exceed 1200–1800 mg. Evidence exists that it may aid in the treatment of T2DM and peripheral neuropathy.

300–1800 mg/d

Alpha-tocopher-ol/vitamin E

B Caution is warranted prior to recommending vitamin E supplementation because of a possible increased risk of death from all causes in patients who take high doses.

400–600 IU/d

Bitter melon C Bitter melon has been studied in humans as an oral and subcutaneous agent; however, safety and efficacy data are not readily available for specific doses. Use cautiously in women of child-bearing age (risk of miscarriage). Also avoid use in nursing women, children, patients with gourd/melon allergies, and those with G6PDH deficiency.

2–3 g/d

Burdock C Given the potential of harvesters to confuse burdock with belladonna alkaloids, purity of burdock preparations cannot be guaranteed; contaminated burdock may produce atropine-like effects. Because of safety concerns and lack of efficacy data, burdock should not be recommended at this time. Avoid use in patients with allergies to ragweed, chrysanthemums, marigolds, daisies, or pectin. Use caution when taken with anticoagulants and antiplatelet agents.

90 g/d

Chromium C Chromium is likely safe when used appropriately. Beneficial effects on glucose in patients with T2DM have been documented; however, the results are inconsistent. Additional research is required before recommending to patients for glycemic control. Administration of H2 blockers may inhibit absorption of chromium. Additionally, coadministration of levothyroxine and chromium should be separated by several hours.

200, 600 mcg/d

500–1000 mcg/d (picolinate)

Cinnamon C When consumed as a spice for food, cinnamon is likely safe and may lower blood glucose values in patients with diabetes. One gram of cinnamon is equal to approximately one-half teaspoonful per day.5 It should be noted, however, that cinnamon is a high-risk allergen. Also, avoid concomitant use with anticoagulants.

1–3 g/d

Dandelion C Dandelion is likely safe when used as naturally found in food products. How-ever, human efficacy data for glycemic-lowering effects is severely lacking.

No human data available

Fenugreek A Fenugreek seed powder has more available positive evidence than other herbal supplements for reducing blood glucose levels in patients with T2DM. Gastro-intestinal effects may be experienced with its use. Space other oral medica-tions apart from fenugreek administration by at least 2 hours.

5–100 g/d(seed powder)

Ginseng C Asian or American ginseng products may have efficacy as glucose-lowering agents; however, the inability to reliably reproduce efficacy results in trials limits the confident recommendation of these agents for glycemic control.

3, 6 g/d, divided into pre-meal doses

Gymnema B It may be safe to recommend gymnema for glycemic lowering in patients with T2DM, but further well-controlled trials need to be conducted. Counsel patients on the potential for enhanced perception of bitter taste.

400 mg/d

Ivy Gourd B Limited data in trials with small sample sizes suggest possible efficacy for glycemic control in patients with T2DM. Ivy gourd is associated with possible minor gastrointestinal effects, but it has no known drug interactions.

1800 mg/d; 6 g/d

Nopal C Nopal is likely safe when consumed as part of a regular diet and may reduce blood glucose and cholesterol levels. Use with caution in patients taking anticoagulants, antiplatelet agents, or agents metabolized through the CYP450 system.

100–600 g/d

Onion C Onion is likely safe when consumed as a part of regular dietary intake. Caution should be exercised when combined with anticoagulants, antiplatelet agents, blood pressure lowering agents, or agents metabolized through the CYP450 system.

20 g fresh onion consumed three times daily; 25, 50, 100, and 200 g aqueous onion extract

Psyllium C (hyperglycemia)

When added to one’s regular diet or used as fiber supplementation, psyllium may benefit glycemic control. Oral medications should be taken 1 hour before or 2 hours after psyllium. Additionally, products containing psyllium should be consumed with adequate amounts of water.

5.2 g seed husk two times daily



Table 1 continued from page 67

Pyridoxine C Pyridoxine is likely safe when used within one’s recommended dietary al-lowance. Dosages greater than 200 mg have been associated with reversible neuropathy.

50–100 mg/d; <200 mg/d recommended

Selenium D(prevention)

Selenium should be avoided in patients on hemodialysis or immunosuppres-sants, as well as in those with hyperlipidemia or hypothyroidism. Selenium may increase risk for the development of T2DM.

<800 mcg/d recommended

Zinc C Limited data is available on the efficacy of zinc in patients with T2DM. Zinc should not be coadministered with fluoroquinolones, tetracyclines, or calcium salts.

600–660 mg/d

Abbreviations used: CYP450, cytochrome P450; G6PDH, glucose-6-phosphate dehydrogenase; T2DM, type 2 diabetes mellitus.aNatural Standard evidence-based grading scale key: A, strong scientific evidence; B, good scientific evidence; C, unclear or conflicting scientific evidence; D, fair negative scientific evidence; F, strong negative scientific evidence.

the type and severity of disease, as well as other agents used for glycemic control. Patients should also be closely moni-tored for adverse events. Optimal doses of natural products are often unclear, many products are not standardized, and extensive variability can be seen from manufacturer to man-ufacturer or batch to batch.

Pharmacists must be able to determine which brands of herbal and dietary supplements can be reliably recommend-ed to consumers and use manufacturer labeling as a dosing guide (Table 2).16 Pharmacists should look for products with recognized symbols of quality (e.g., United States Pharmaco-peia and the National Formulary, TruLabel, Consumer Lab) and avoid recommending foreign products unless the qual-ity is known.8

ConclusionMore than 400 herbal agents have been identified for their potential antihyperglycemic effects.11,21 However, there is no conclusive evidence that these agents are safer or more ef-fective than other agents currently used in modern medical practice. Pharmacists should encourage patients to seek ad-vice about the addition of these agents for the management of diabetes and consider these agents as adjuncts to pharma-cologic treatment.

Though limited data are available for the use of herbals and dietary supplements for diabetes care, health care con-sumers continue to turn to these agents as a means of supple-mentation and/or management of their disease state. It is es-sential that pharmacists recognize safety and efficacy issues prior to recommending herbals and dietary supplements for diabetes care.

References1. Vuksan V, Sievenpiper JL. Herbal remedies in the management of

diabetes: lessons learned from the study of ginseng. Nutr Metab Cardiovasc Dis. 2005;15(3):149–160.

2. Bailey RL, Gahche JJ, Lentino CV, et al. Dietary supplement use in the United States, 2003–2006. J. Nutr. 2011;141(2):261–266.

3. Gahche J, Bailey R, Burt V, et al. Dietary supplement use among U.S. adults has increased since NHANES III (1988–1994). NCHS

Data Brief. 2011;61:1–8. 4. Kennedy J. Herb and supplement use in the US adult population.

Clin Ther. 2005;27(11):1847–1858.5. Geil P, Shane-McWhorter L. Dietary supplements in the manage-

ment of diabetes: potential risks and benefits. J Am Diet Assoc.

2008;108(4 Suppl 1):S59–S65.

Table 2. Elements that should be clearly identified on herbal and dietary supplement products prior to pharmacist recommendation

Common or scientific name of productDosage of the botanicalPart of the plant from which it was madeActive and other ingredientsManufacturer’s name and address, lot number, and date of manufacture and expiration

6. Dietary Supplement Health and Education Act of 1994, PL 103-417, 108 Stat 4325.

7. U.S. Food and Drug Administration. Dietary supplements. www.fda.gov/Food/DietarySupplements/default.htm. Accessed Janu-ary 29, 2014.

8. Yeh GY, Eisenberg DM, Kaptchuk TJ, et al. Systematic review of herbs and dietary supplements for glycemic control in diabetes. Dia-

betes Care. 2003;26(4):1277–1294.9. Shapiro K, Gong WC. Natural products used for diabetes. J Am

Pharm Assoc. 2002:42(2):217–226.10. Yeh GY, Eisenberg DM, Davis RB, et al. Use of complementary and

alternative medicine among persons with diabetes mellitus: results

of a national survey. Am J Public Health. 2002;92(10):1648–1652.11. Modak M, Dixit P, Londhe J, et al. Indian herbs and herbal

drugs used for the treatment of diabetes. J Clin Biochem Nutr.

2007;40(3):163–173.12. Grover JK, Yadav S, Vats V. Medicinal plants of India with anti-dia-

betic potential. J Ethnopharmacol. 2002;81(1):81–100.13. Garrow D, Egede LE. Association between complementary and al-

ternative medicine use, preventive care practices, and use of con-ventional medical services among adults with diabetes. Diabetes Care. 2006;29(1):15–19.

14. Bell RA, Suerken CK, Grzywacz JG, et al. Complementary and al-ternative medicine use among adults with diabetes in the United

States. Altern Ther in Health Med.2006;12(5):16–22.15. Cicero AF, Derosa G, Gaddi A. What do herbalists suggest to diabet-

ic patients in order to improve glycemic control? Evaluation of scien-

tific evidence and potential risks. Acta Diabetol. 2004;41(3):91–98.16. Natural Standard. https://naturalmedicines.therapeuticresearch.

com. Accessed January 29, 2014.17. Dans AM, Villarruz MV, Jimeno CA, et al. The effect of Momordica

charantia capsule preparation on glycemic control in type 2 diabetes

mellitus needs further studies. J Clin Epidemiol. 2007;60(6):554–559.



18. Fuangchan A, Sonthisombat P, Seubnukarn T, et al. Hypoglycemic effect of bitter melon compared with metformin in newly diagnosed type 2 diabetes patients. J Ethnopharmacol. 2011;134(2):422–428.

19. Chan, YS, Cheng LN, Wu JH, et al. A review of the pharmaco-logical effects of Arctium lappa (burdock). Inflammopharmacol-ogy.2011;19(5):245–254.

20. Nahas R, Moher M. Complementary and alternative medicine for the

treatment of type 2 diabetes. Can Fam Physician. 2009;55(6):591–596.

21. Suksomboon N, Poolsup N, Boonkaew S, et al. Meta-analysis of the effect of herbal supplement on glycemic control in type 2 diabetes.

J Ethnopharmacol. 2011;137(3):1328–1333.22. Allen RW, Schwartzman E, Baker WL, et al. Cinnamon use in type

2 diabetes: an updated systematic review and meta-analysis. Ann

Fam Med. 2013;11(5):452–459.23. Khan A, Safdar M, Ali Khan MM, et al. Cinnamon improves glu-

cose and lipids of people with type 2 diabetes. Diabetes Care.

2003;26(12):3215–3218.24. Leach MJ, Kumar S. Cinnamon for diabetes mellitus. Cochrane Da-

tabase Syst Rev. 2012;9:CD007170.25. Goksu E, Eken C, Karadeniz O, et al. First report of hypoglycemia

secondary to dandelion (Taraxacum officinale) ingestion. Am J Emerg Med. 2010;28(1):111.e1–111.e2.

26. Neelakantan N, Narayanan M, de Souza RJ, et al. Effect of fenu-greek (Trigonella foenum-graecum L.) intake on glycemia: a meta-analysis of clinical trials. Nutr J. 2014;13:7.

27. Hays NP, Galassetti PR, Coker RH. Prevention and treatment of type 2 diabetes: current role of lifestyle, natural product, and phar-

macological interventions. Pharmacol Ther. 2008;118(2):181–191.28. Vuksan V, Sung MK, Sievenpiper JL, et al. Korean red ginseng

(Panax ginseng) improves glucose and insulin regulation in well-controlled, type 2 diabetes: results of a randomized, double-blind, placebo-controlled study of efficacy and safety. Nutr Metab Cardio-

vas Dis. 2008;18(1):46–56.29. Baskaran K, Kizar Ahamath B, Radha Shanmugasundaram K, et

al. Antidiabetic effect of a leaf extract from Gymnema sylvestre in non-insulin-dependent diabetes mellitus patients. J Ethnopharma-

col. 1990;30(3):295–300.30. Kuriyan R, Rajendran R, Bantwal G, et al. Effect of supplementation

of Coccinia cordifolia extract on newly detected diabetic patients. Diabetes Care. 2008;31(2):216–220.

31. Shekelle PG, Hardy M, Morton SC, et al. Are Ayurvedic herbs for

diabetes effective? J Fam Pract. 2005;54(10):876–886.32. Kamble SM, Jyotishi GS, Kamalakar PL, et al. Efficacy of Coccinia

indica W & A in diabetes mellitus. J Res Ayur Sid. 1996;17:77–84.33. American Diabetes Association. Standards of medical care in dia-

betes—2014. Diabetes Care. 2014;37(Suppl 1):s14-s80.34. Hall M, Flinkman T. Do fiber and psyllium fiber improve diabetic me-

tabolism? Consult Pharm. 2012;27(7):513–516.35. AbouZid SF, Ahmed OM, Ahmed RR, et al. Antihyperglycemic effect

of crude extracts of some Egyptian plants and algae. J Med Food.

2014;17(3):400–406.36. Anderson JW, Allgood LD, Turner J, et al. Effects of psyllium on

glucose and serum lipid responses in men with type 2 diabetes and

hypercholesterolemia. Am J Clin Nutr. 1999;70(4):466–473.37. Ziai SA, Larijani B, Akhoondzadeh S, et al. Psyllium decreased se-

rum glucose and glycosylated hemoglobin significantly in diabetic

outpatients. J Ethnopharmacol. 2005;102(2):202–207.38. Natural Medicines Comprehensive Database. http://naturaldata-

base.therapeuticresearch.com. Accessed February 1, 2014. 39. Ziegler D, Ametov A, Barinov A, et al. Oral treatment with alpha-li-

poic acid improves symptomatic diabetic polyneuropathy: the SYD-

NEY 2 trial. Diabetes Care. 2006;29(11):2365–2370.

40. Ziegler D, Nowak H, Kempler P, et al. Treatment of symptomatic dia-betic polyneuropathy with the antioxidant alpha-lipoic acid: a meta-

analysis. Diabet Med. 2004;21(2):114–121.41. Konrad T, Vicini P, Kusterer K, et al. Alpha-lipoic acid treatment de-

creases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with type 2 diabe-

tes. Diabetes Care. 1999;22(2):280–287.42. Jacob S, Henriksen EJ, Schiemann AL, et al. Enhancement of glu-

cose disposal in patients with type 2 diabetes by alpha-lipoic acid.

Arzneimittelforschung. 1995;45(8):872–874. 43. Jacob S, Ruus P, Hermann R, et al. Oral administration of RAC-

alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial. Free Radic Biol

Med. 1999;27:309–314.44. Kamenova P. Improvement of insulin sensitivity in patients with type

2 diabetes mellitus after oral administration of alpha-lipoic acid. Hor-

mones. 2006;5(4):251–258.45. Bartlett HE, Eperjesi F. Nutritional supplementation for type 2 diabe-

tes: a systematic review. Ophthalmic Physiol Opt. 2008;28(6):503–523.

46. Mazloom Z, Ansar H. The effect of alpha-lipoic acid on blood pres-

sure in type 2 diabetics. Iran J Endocrinol Metab. 2009;11(3):245–250.

47. Ziegler D, Hanefeld M, Ruhnau KJ, et al. Treatment of symptom-atic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III Study).

Diabetes Care. 1999;22(8):1296–1301.48. Reljanovic M, Reichel G, Rett K, et al. Treatment of diabetic poly-

neuropathy with the antioxidant thioctic acid (alpha-lipoic acid): a two year multicenter randomized double-blind placebo-controlled

trial (ALADIN II). Free Radic Res. 1999;31(3):171–179.49. Ametov AS, Barinov A, Dyck PJ, et al. The sensory symptoms of

diabetic polyneuropathy are improved with alpha-lipoic acid: the

SYDNEY trial. Diabetes Care. 2003;26(3):770–776.50. McIIduff CE, Rutkove SB. Critical appraisal of the use of alpha lipoic

acid (thiotic acid) in the treatment of symptomatic diabetic polyneu-

ropathy. Ther Clin Risk Manag. 2011;7:377–385.51. Ziegler D, Gries FA. Alpha-lipoic acid in the treatment of diabetic pe-

ripheral and cardiac autonomic neuropathy. Diabetes. 1997;46(Sup-

pl 2):S62–S66.52. Han T, Bai J, Liu W, et al. A systematic review and meta-analysis of

alpha-lipoic acid in the treatment of diabetic peripheral neuropathy.

Eur J Endocrinol. 2012;167(4):465–471.53. Haritoglou C, Gerss J, Hammes HP, et al. Alpha-lipoic acid for

the prevention of diabetic macular edema. Ophthalmologica.

2011;226(3):127–137.54. de Oliveira AM, Rondo PH, Luzia LA, et al. The effects of lipoic acid

and alpha-tocopherol supplementation on the lipid profile and insu-lin sensitivity of patients with type 2 diabetes mellitus: a random-ized, double-blind, placebo-controlled trial. Diabetes Res Clin Pract.

2011;92(2):253–260.55. Sano M, Ernesto C, Thomas RG, et al. A controlled trial of selegiline,

alpha-tocopherol, or both as treatment for Alzheimer’s disease. N

Engl J Med. 1997;336(17):1216–1222.56. Montonen J, Knekt P, Jarvinen R, et al. Dietary antioxidant intake

and risk of type 2 diabetes. Diabetes Care. 2004;27(2):362–366. 57. Arnlov J, Zethelius B, Riserus U, et al. Serum and dietary beta-caro-

tene and alpha-tocopherol and incidence of type 2 diabetes mellitus in a community-based study of Swedish men: report from the Up-psala Longitudinal Study of Adult Men (ULSAM) study. Diabetolo-

gia. 2009;52(1):97–105.



58. Bursell SE, Clermont AC, Aiello LP, et al. High-dose vitamin E sup-plementation normalizes retinal blood flow and creatinine clearance

in patients with type 1 diabetes. Diabetes Care. 1999;22(8):1245–1251.

59. Tutuncu NB, Bayraktar M, Varli K. Reversal of defective nerve con-duction with vitamin E supplementation in type 2 diabetes: a prelimi-

nary study. Diabetes Care. 1998;21(11):1915–1918.60. Paolisso G, D’Amore A, Giugliano D, et al. Pharmacologic doses of

vitamin E improve insulin action in healthy subjects and non-insulin-

dependent diabetic patients. Am J Clin Nutr. 1993;57(5):650–656.61. Blum S, Vardi M, Brown JB, et al. Vitamin E reduces cardiovascular

disease in individuals with diabetes mellitus and the haptoglobin 2-2

genotype. Pharmacogenomics. 2010;11(5):675–684. 62. Vardi M, Blum S, Levy AP. Haptoglobin genotype and cardiovas-

cular outcomes in diabetes mellitus- natural history of the disease and the effect of vitamin E treatment. Meta-analysis of the medical

literature. Eur J Intern Med. 2012;23(7):628–632. 63. Suksomboon N, Poolsup N, Sinprasert S. Effects of vitamin E

supplementation on glycaemic control in type 2 diabetes: sys-tematic review of randomized controlled trials. J Clin Pharm Ther.

2011;36(1):53–63.64. Gomez-Perez FJ, Valles-Sanchez VE, Lopez-Alvarenga JC, et al.

Vitamin E modifies neither fructosamine nor HbA1c levels in poorly

controlled diabetes. Rev Invest Clin. 1996;48(6):421–424.65. Ble-Castillo JL, Carmona-Diaz E, Mendez JD, et al. Effect of alpha-

tocopherol on the metabolic control and oxidative stress in female

type 2 diabetics. Biomed Pharmacother. 2005;59(6):290–295.66. Kataja-Tuomola M, Sundell JR, Mannisto S, et al. Effect of alpha-

tocopherol and beta-carotene supplementation on the incidence of

type 2 diabetes. Diabetologia. 2008;51(1):47–53. 67. Yusuf S, Dagenais G, Pogue J, et al. Vitamin E supplementation

and cardiovascular events in high risk patients. N Engl J Med. 2000;342(3):154–160.

68. Albarracin CA, Fuqua BC, Evans JL, et al. Chromium picolinate and biotin combination improves glucose metabolism in treated, uncon-trolled overweight to obese patients with type 2 diabetes. Diabetes

Metab Res Rev. 2008;24(1):41–51.69. Balk EM, Tatsioni A, Lichtenstein AH, et al. Effect of chromium sup-

plementation on glucose metabolism and lipids: a systematic review

of randomized controlled trials. Diabetes Care. 2007;30(8):2154–2163.

70. Kleefstra N, Houweling ST, Jansman FG, et al. Chromium treatment has no effect in patients with poorly controlled, insulin-treated type 2 diabetes in an obese Western population: a randomized, double-

blind, placebo-controlled trial. Diabetes Care. 2006;29(3):521–525.71. Kleefstra N, Houweling ST, Bakker SJ, et al. Chromium treatment

has no effect in patients with type 2 diabetes in a Western popula-tion: a randomized, double-blind, placebo-controlled trial. Diabetes

Care. 2007;30(5):1092–1096.72. Singer GM, Geohas J. The effect of chromium picolinate and biotin

supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded,

randomized trial. Diabetes Technol Ther. 2006;8(6):636–643.73. Anderson RA, Cheng N, Bryden NA, et al. Elevated intakes of

supplemental chromium improve glucose and insulin variables in

individuals with type 2 diabetes. Diabetes. 1997;46(11):1786–1791.

74. Pei D, Hsieh CH, Hung YJ, et al. The influence of chromium chlo-ride-containing milk to glycemic control of patients with type 2 dia-betes mellitus: a randomized, double-blind, placebo-controlled trial.

Metabolism. 2006;55(7):923–927.75. Krol E, Krejpcio Z, Byks H, et al. Effects of chromium brewer’s

yeast supplementation on body mass, blood carbohydrates, and lipids and minerals in type 2 diabetic patients. Biol Trace Elem Res.

2011;143(2):726–737.76. Jain SK, Kahlon G, Morehead L, et al. Effect of chromium dinicocys-

teinate supplementation on circulating levels of insulin, TNF-alpha, oxidative stress, and insulin resistance in type 2 diabetic subjects: randomized, double-blind, placebo-controlled study. Mol Nutr Food

Res. 2012;56(8):1333–1341.77. Althuis MD, Jordan NE, Ludington EA, et al. Glucose and insulin

responses to dietary chromium supplements: a meta-analysis. Am

J Clin Nutr. 2002;76(1):148–155.78. Head KA. Peripheral neuropathy: pathogenic mechanisms and al-

ternative therapies. Altern Med Rev. 2006;11(4):294–329.79. Levin ER, Hanscom TA, Fisher M, et al. The influence of pyridoxine

in diabetic peripheral neuropathy. Diabetes Care. 1981;4(6):606–609.

80. Abbas ZG, Swai AB. Evaluation of the efficacy of thiamine and pyri-doxine in the treatment of symptomatic diabetic peripheral neuropa-

thy. East Afr Med J. 1997;74(12):803–808.81. Rao RH. Glucose tolerance in subclinical pyridoxine deficiency in

man. Am J Clin Nutr. 1983;38(3):440–444.82. Rao RH, Vigg BL, Rao KS. Failure of pyridoxine to improve glucose

tolerance in diabetics. J Clin Endocrinol Metab. 1980;50(1):198–200.

83. Stranges S, Marshall JR, Natarajan R, et al. Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a

randomized trial. Ann Intern Med. 2007;147(4):217–223. 84. Bleys J, Miller ER III, Pastor-Barriuso R, et al. Vitamin-mineral sup-

plementation and the progression of atherosclerosis: a meta-analy-

sis of randomized controlled trials. Am J Clin Nutr. 2006;84(4):880–887.

85. Akbaraly TN, Arnaud J, Rayman MP, et al. Plasma selenium and risk of dysglycemia in an elderly French population: results from the prospective Epidemiology of Vascular Ageing Study. Nutr Metab. 2010;7:21.

86. Blostein-Fujii A, DiSilvestro RA, Frid D, et al. Short-term zinc sup-plementation in women with non-insulin-dependent diabetes mel-litus: effects on plasma 5’-nucleotidase activities, insulin-like growth factor I concentrations, and lipoprotein oxidation rates in vitro. Am J

Clin Nutr. 1997;66(3):639–642.87. Tang X, Shay NF. Zinc has an insulin-like effect on glucose transport

mediated by phosphoinositol-3-kinase and Akt in 3T3-L1 fibroblasts

and adipocytes. J Nutr. 2001;131(5):1414–1420.88. Dennehy CE, Tsourounis C, Horn AJ. Dietary supplement-related

adverse events reported to the California Poison Control System.

Am J Health Syst Pharm. 2005;62(14):1476–1482.89. Gupta R, Garg VK, Mathur DK, et al. Oral zinc therapy in diabetic

neuropathy. J Assoc Physicians India. 1998;46(11):939–942.



1. Which botanical agent is a known abortifacient?a. Burdockb. Bitter melonc. Fenugreekd. Gymnema

2. Due to theoretical concerns, dandelion use should be avoided in patients with:a. Gastric ulcersb. Pancreatitisc. Anemiad. Liver disease

3. An important counseling point for consumers wish-ing to purchase gymnema would be:a. Significant potential for weight gainb. Enhanced perception of bitter tastec. Avoid combination with anticoagulantsd. Take 40 minutes prior to meals

4. Based on available data, which agent has good scien-tific evidence for glucose-lowering efficacy?a. Gymnemab. Onionc. Cinnamond. Nopal

5. Which herbal agent is more likely to increase bleeding risk when used concomitantly with anticoagulants?a. Bitter melonb. Burdockc. Cinnamond. Fenugreek

6. Which agent has a more notable drug–drug interaction with dandelion?a. Calcium carbonateb. Furosemidec. Ciprofloxacind. Orlistat

CPE InformationTo obtain 2.0 contact hours (0.2 CEUs) of CPE credit for this activity, you must complete the assessment and evaluation. CPE credit will be awarded for a passing grade of 70% or better on the assessment. You will have two opportunities to successfully complete the CPE assess-ment. Pharmacists who successfully complete this activity before August 1, 2017, can receive CPE credit. CPE credit is achieved upon successful completion of the assessment and evaluation. Your transcript will be stored on CPE Monitor. Please visit CPE Monitor for your transcript at www.nabp.net/programs/cpe-monitor/cpe-monitor-service.

CPE instructions:1. Log in or create an account at pharmacist.com and select LEARN from the top of the page; select Continuing Education, then Home Study CPE

to access the Library.2. Enter the title of this article or the ACPE number to search for the article and click on the title of the article to start the home study.3. To receive CPE credit, select Enroll Now from the left navigation and successfully complete the assessment (with randomized questions) and

evaluation. 4. To obtain your CPE credit, click “Claim” on the right side of the page. You will need to provide your NABP e-profile ID number to obtain your

CPE credit. Your CPE transcripts will be stored on CPE Monitor. Live step-by-step assistance is available Monday through Friday, 8:30 am to 5:00 pm ET from APhA Member Services at 800-237-APhA (2742) or by e-mailing [email protected].

CPE AssessmentInstructions: This exam must be taken online; please see “CPE information” for further instructions. The online system will present these questions in random order to help reinforce the learning opportunity. There is only one correct answer to each question.

7. A female with T2DM asks for an herbal supplement to use as an adjunct to her metformin therapy for gly-cemic control. She takes no other medications and has no other disease states at this time. Based on the avail-able safety and efficacy data, which herbal supplement would be the most appropriate to recommend?a. Burdockb. Dandelionc. Fenugreekd. Ivy gourd

8. Which statement is true regarding ginseng?a. Siberian ginseng is an acceptable alternative to

Panax ginseng.b. Studies have demonstrated efficacy when given 40

minutes after meals.c. Products are standardized according to the ginsen-

osides and their ratios.d. Doses of 1–9 grams have reduced blood

glucose values acutely and long term.9. Which agent has demonstrated hypoglycemic effects

comparable to tolbutamide when given as a single oral dose?a. Dandeliob. Onionc. Cinnamond. Psyllium

10. Which agent should be cautiously recommended in persons with cardiovascular disease because of the potential for contamination during harvesting?a. Bitter melonb. Burdockc. Fenugreekd. Dandelion



11. A reliable brand of herbal supplements to recommend will contain:a. Manufacturer’s phone numberb. Notice of FDA approvalc. Treatment statement for conditiond. Recognized symbol of quality

12. Which dietary supplement has data that demonstrate a possible benefit in A1C reduction in patients with T2DM?a. Chromiumb. Pyridoxinec. Seleniumd. Zinc

13. Which fat-soluble vitamin has evidence suggesting that use of high doses may increase the risk of death and, thus, should not be recommended for manage-ment of T2DM?a. Pyridoxineb. Alpha-tocopherolc. Alpha-lipoic acidd. Zinc

14. Which should be avoided in patients being treated for Parkinson disease?a. Seleniumb. Chromiumc. Alpha-lipoic acidd. Pyridoxine

15. A patient (JM) approaches your community pharmacy counter to ask about appropriate administration of chromium. She would like to try supplemental chro-mium to aid in glycemic control of her T2DM. You in-form her that that additional research is needed before you can recommend chromium for glycemic control, but she would still like to try the supplement. JM also has hypothyroidism and frequent heartburn. Which counseling point would you provide JM?a. Use of levothyroxine and chromium should be

separated by several hours.b. Chromium should be administered at the same time

as JM’s ranitidine for maximum absorption.c. Chromium is contraindicated in patients with hy-

pothyroidism.d. Chromium is contraindicated in patients taking

metformin.16. A 62-year-old male patient started alpha-lipoic acid

300 mg daily and pyridoxine 800 mg daily for treat-ment of his T2DM approximately 8 months ago. He also takes metformin 1500 mg daily. His blood sugar seems to be well controlled at this time. However, he is complaining of peripheral neuropathy pain today. He would like to know what could be causing this new symptom. Which is the most appropriate answer?a. Alpha-lipoic acid has been proven to effectively treat

neuropathy; thus, he should continue all of his cur-rent therapies at the current dose.

b. Higher doses (>200 mg) of pyridoxine have been associated with reversible neuropathy. He should discontinue the pyridoxine and see his primary care provider.

c. Higher doses (>200 mg) of alpha-lipoic acid have been associated with reversible neuropathy. He should discontinue the alpha-lipoic acid and see his primary care provider.

d. Peripheral neuropathy is a complication of T2DM. None of his current therapies have any effect on symptoms of neuropathy.

17. A patient at your pharmacy would like to start taking selenium to help prevent T2DM. Her mother and two of her siblings have T2DM, and she is very concerned about her risk for the disease. She currently has hypertension and hyperlipidemia. What would you recommend for this patient?a. She should start selenium immediately to help pre-

vent T2DM and to aid in treatment of her hyperlip-idemia.

b. Prior to starting selenium therapy, she should have the concentration of selenium in her toenails deter-mined. If her concentration is high, she should start selenium supplementation.

c. She should not take selenium as a supplemental therapy. Data demonstrate an increased risk for the development of T2DM in patients taking selenium. Additionally, selenium should be avoided in patients with hyperlipidemia.

d. She should not take selenium for prevention of T2DM; however, if she is diagnosed with T2DM, she should begin selenium supplementation to aid in glycemic control.

18. Which supplement has been implicated as a risk factor for the development of insulin autoimmune syn-drome?a. Alpha-lipoic acidb. Chromiumc. Oniond. Pyridoxine

19. Which statement regarding vitamin E is false?a. Caution is warranted with the use of high-dose vita-

min E because of a possible increased risk of death from all causes.

b. Vitamin E should be avoided in patients taking anticoagulants.

c. Vitamin E has been shown to significantly reduce A1C levels in patients with T2DM in randomized, placebo-controlled clinical trials.

d. Vitamin E should be avoided in patients taking cyclosporine.

20. Which adverse event is frequently reported with the use of supplemental zinc?a. Nausea b. Encephalitisc. Hemorrhaged. Congenital heart defects

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