Pharmacology Consult

Dietary supplements: the good, bad and ugly

As health care providers, our patients frequently ask questions about what supplements could help their diabetes or other health problems. Some supplements may be helpful for their diabetes or overall health, but others may be deleterious. Dietary supplements include vitamins, minerals, herbs or other botanicals, amino acids, a dietary substance for use by humans to supplement the diet by increasing the total dietary intake, or a concentrate, metabolite, constituent, or extract.

This article will focus on information related to supplements other than herbals, as that will be the subject of a future column.

The good, possibly good

Alpha-Lipoic Acid is a cofactor in many enzyme complexes, a potent antioxidant and appears to be involved in glucose oxidation. It is reported to have beneficial effects on insulin sensitivity and glucose uptake in oral divided doses ranging from 600 mg to 1,800 mg a day and is well tolerated, but more studies are needed. Studies suggest a role in reducing diabetic neuropathy due to its role in improving the pathogenesis of diabetic polyneuropathy through its reduction in oxidative stress.

Omega-3 fatty acid (EPA + DHA) is a highly unsaturated fatty acid present in cold-water fish and available commercially as fish oil capsules or a prescription product called Omacor (Reliant Pharms). In daily doses of 3 g to 12 g, it can decrease triglyceride concentrations by 20% to 50%, reduce LDL by 5% to 10%, and can increase HDL by 1% to 3%. An American Heart Association Scientific Statement supports the use of this product in view of solid evidence from epidemiological and clinical trials of a reduction in cardiovascular disease.

June Felice Johnson, PharmD, FASHP, CDM-diabetes
June Felice Johnson

Chromium is an essential mineral that is required for normal lipid and glucose homeostasis. The optimal form of oral chromium is the trivalent picolinate formulation designed to improve absorption. A recent meta-analysis of 41 studies, almost half of which had poor quality design, suggested that HbA1c was reduced by an average of 0.6% in patients with type 2 diabetes. Doses of the picolinate formulation ranged from 60 mcg to 1,000 mcg a day. However, the reduction in HbA1c appeared mainly in non-Western populations and there were many limitations in the studies reviewed. Studies suggesting chromium is effective at reducing the occurrence of diabetes in people at risk have been inconclusive. Also, there is still no reliable test to determine which patients are genuinely deficient.

The American Diabetes Association’s current position statement on nutrition states that there is “no clear evidence of benefit from vitamin or mineral supplementation in people with diabetes” in the absence of underlying deficiencies.

The bad, the ugly

The ADA’s position statement also states that routine supplementation with vitamins E, C and carotene is not advised due to lack of efficacy evidence and concerns for long-term safety.

The antioxidant vitamins A, E, C, and beta carotene are not recommended for primary or secondary prevention of CVD. Although vitamin E has potent antioxidant activity and may affect nonoxidative glucose metabolism, recent clinical trials have actually indicated increased morbidity due to increased risk of heart failure. Only small, inconclusive trials have been conducted in people with diabetes.

Vanadium is a trace element not established as an essential nutrient. It appears to be an insulinomimetic and may increase insulin activity and sensitivity. Unfortunately clinical trials have been too small to be conclusive. Avoidance of its use is advised, as relatively small exogenously administered doses are potentially toxic since body stores are very low (100 mcg). Adverse effects include nausea, vomiting, cramping, flatulence and diarrhea.

Caveats for patients, providers

The regulatory framework for dietary supplements is DSHEA — Dietary Supplement Health and Education Act — signed into law in 1994. Unfortunately, as a result of DSHEA, supplements do not need FDA approval for marketing nor do manufacturers have to provide the FDA with evidence of safety or effectiveness for these products. In addition, Good Manufacturing Practice regulations are completely voluntary for manufacturers, leading to concerns for consistency in product potency, purity and quality.

All of us should apply the Latin phrase “caveat emptor” (“buyer beware”) to dietary supplements given the lack of regulation and paucity of well-designed clinical studies. Patients are counting on us to ensure that the supplements they are taking have consistent and reliable quality, have some evidence of effectiveness, and are not detrimental to their diabetes care or other health problems.

June Felice Johnson, BS, PharmD, FASHP, CDM-Diabetes, is the Director of Faculty & Site Development and Associate Professor of Pharmacy Practice at Drake University College of Pharmacy & Health Sciences, Des Moines, Iowa.

For more information:
  • AHA Scientific Statement. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002;106:2747-57.
  • Balk EM, Tatsioni A, Lichtenstein AH, et al. Effect of chromium supplementation on glucose metabolism and lipids. Diabetes Care. 2007;30:2154-2163.
  • Foster TS. Efficacy and safety of a-lipoic acid supplementation in the treatment of symptomatic diabetic neuropathy. Diabetes Educ. 2007;33:111-117.
  • O’Connell BS. Select vitamins and minerals in the management of diabetes. Diabetes Spectrum. 2001;14:133-148.
  • Pharmacist’s Letter/Prescriber’s Letter. Summary of 2007 AHA evidence-based guidelines for cardiovascular disease prevention in women. April 2007;23:No. 230403.
  • Position Statement. Nutrition recommendations and interventions for diabetes. American Diabetes Association. Diabetes Care. 2008;31:S61-S78.
  • The HOPE and HOPE-TOO Trial Investigators. Effects of long-term Vitamin E supplementation on cardiovascular events and cancer. JAMA. 2005;293:1338-1347.
  • The SYDNEY Trial. The sensory symptoms of diabetic polyneuropathy are improved with a-lipoic acid. Diabetes Care. 2003;26:770-776.
  • Yeh GY, Eisenberg DM, Kaptchuk TJ, et al. Systematic review of herbs and dietary supplements for glycemic control in diabetes. Diabetes Care. 2003;26:1277-1294.

As health care providers, our patients frequently ask questions about what supplements could help their diabetes or other health problems. Some supplements may be helpful for their diabetes or overall health, but others may be deleterious. Dietary supplements include vitamins, minerals, herbs or other botanicals, amino acids, a dietary substance for use by humans to supplement the diet by increasing the total dietary intake, or a concentrate, metabolite, constituent, or extract.

This article will focus on information related to supplements other than herbals, as that will be the subject of a future column.

The good, possibly good

Alpha-Lipoic Acid is a cofactor in many enzyme complexes, a potent antioxidant and appears to be involved in glucose oxidation. It is reported to have beneficial effects on insulin sensitivity and glucose uptake in oral divided doses ranging from 600 mg to 1,800 mg a day and is well tolerated, but more studies are needed. Studies suggest a role in reducing diabetic neuropathy due to its role in improving the pathogenesis of diabetic polyneuropathy through its reduction in oxidative stress.

Omega-3 fatty acid (EPA + DHA) is a highly unsaturated fatty acid present in cold-water fish and available commercially as fish oil capsules or a prescription product called Omacor (Reliant Pharms). In daily doses of 3 g to 12 g, it can decrease triglyceride concentrations by 20% to 50%, reduce LDL by 5% to 10%, and can increase HDL by 1% to 3%. An American Heart Association Scientific Statement supports the use of this product in view of solid evidence from epidemiological and clinical trials of a reduction in cardiovascular disease.

June Felice Johnson, PharmD, FASHP, CDM-diabetes
June Felice Johnson

Chromium is an essential mineral that is required for normal lipid and glucose homeostasis. The optimal form of oral chromium is the trivalent picolinate formulation designed to improve absorption. A recent meta-analysis of 41 studies, almost half of which had poor quality design, suggested that HbA1c was reduced by an average of 0.6% in patients with type 2 diabetes. Doses of the picolinate formulation ranged from 60 mcg to 1,000 mcg a day. However, the reduction in HbA1c appeared mainly in non-Western populations and there were many limitations in the studies reviewed. Studies suggesting chromium is effective at reducing the occurrence of diabetes in people at risk have been inconclusive. Also, there is still no reliable test to determine which patients are genuinely deficient.

The American Diabetes Association’s current position statement on nutrition states that there is “no clear evidence of benefit from vitamin or mineral supplementation in people with diabetes” in the absence of underlying deficiencies.

The bad, the ugly

The ADA’s position statement also states that routine supplementation with vitamins E, C and carotene is not advised due to lack of efficacy evidence and concerns for long-term safety.

The antioxidant vitamins A, E, C, and beta carotene are not recommended for primary or secondary prevention of CVD. Although vitamin E has potent antioxidant activity and may affect nonoxidative glucose metabolism, recent clinical trials have actually indicated increased morbidity due to increased risk of heart failure. Only small, inconclusive trials have been conducted in people with diabetes.

Vanadium is a trace element not established as an essential nutrient. It appears to be an insulinomimetic and may increase insulin activity and sensitivity. Unfortunately clinical trials have been too small to be conclusive. Avoidance of its use is advised, as relatively small exogenously administered doses are potentially toxic since body stores are very low (100 mcg). Adverse effects include nausea, vomiting, cramping, flatulence and diarrhea.

Caveats for patients, providers

The regulatory framework for dietary supplements is DSHEA — Dietary Supplement Health and Education Act — signed into law in 1994. Unfortunately, as a result of DSHEA, supplements do not need FDA approval for marketing nor do manufacturers have to provide the FDA with evidence of safety or effectiveness for these products. In addition, Good Manufacturing Practice regulations are completely voluntary for manufacturers, leading to concerns for consistency in product potency, purity and quality.

All of us should apply the Latin phrase “caveat emptor” (“buyer beware”) to dietary supplements given the lack of regulation and paucity of well-designed clinical studies. Patients are counting on us to ensure that the supplements they are taking have consistent and reliable quality, have some evidence of effectiveness, and are not detrimental to their diabetes care or other health problems.

June Felice Johnson, BS, PharmD, FASHP, CDM-Diabetes, is the Director of Faculty & Site Development and Associate Professor of Pharmacy Practice at Drake University College of Pharmacy & Health Sciences, Des Moines, Iowa.

For more information:
  • AHA Scientific Statement. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002;106:2747-57.
  • Balk EM, Tatsioni A, Lichtenstein AH, et al. Effect of chromium supplementation on glucose metabolism and lipids. Diabetes Care. 2007;30:2154-2163.
  • Foster TS. Efficacy and safety of a-lipoic acid supplementation in the treatment of symptomatic diabetic neuropathy. Diabetes Educ. 2007;33:111-117.
  • O’Connell BS. Select vitamins and minerals in the management of diabetes. Diabetes Spectrum. 2001;14:133-148.
  • Pharmacist’s Letter/Prescriber’s Letter. Summary of 2007 AHA evidence-based guidelines for cardiovascular disease prevention in women. April 2007;23:No. 230403.
  • Position Statement. Nutrition recommendations and interventions for diabetes. American Diabetes Association. Diabetes Care. 2008;31:S61-S78.
  • The HOPE and HOPE-TOO Trial Investigators. Effects of long-term Vitamin E supplementation on cardiovascular events and cancer. JAMA. 2005;293:1338-1347.
  • The SYDNEY Trial. The sensory symptoms of diabetic polyneuropathy are improved with a-lipoic acid. Diabetes Care. 2003;26:770-776.
  • Yeh GY, Eisenberg DM, Kaptchuk TJ, et al. Systematic review of herbs and dietary supplements for glycemic control in diabetes. Diabetes Care. 2003;26:1277-1294.