Alpha-lipoic acid (ALA). ALA is a chemical compound that is found in food (especially high in spinach, broccoli, and tomatoes), produced endogenously, and sold as a nutritional supplement. As an antioxidant, ALA may mitigate high levels of oxidative stress, which in patients with diabetes contributes to insulin resistance and secondary complications such as diabetic neuropathy.40
Acute intravenous ALA therapy (1–10 days) has been reported to improve insulin sensitivity.41,42 A randomized, placebo-controlled trial of ALA supplementation in patients with type 2 diabetes43 showed a 25% increase in insulin sensitivity after 4 weeks of ALA therapy at doses of 600–1,800 mg. The long-term effects of ALA have yet to be determined, although one study of patients with type 2 diabetes showed improved glycemic control after 12 weeks of therapy.44
Chromium. As an essential mineral, chromium plays an important role in facilitating glucose metabolism. Whole grains, egg yolks, broccoli, and brewer’s yeast have high quantities of chromium.45 Although rare, severe states of chromium deficiency are associated with reversible diabetes because of insulin resistance.46,47 These observations have fueled marketing of chromium for individuals with diabetes who are not necessarily deficient in chromium to increase insulin sensitivity.
A meta-analysis of 14 RCTs48 of patients with type 2 diabetes (n = 381) concluded that there were significant changes in glucose metabolism after supplementation with chromium. Overall, the authors emphasized the poor quality of studies and the need for further research. Reports suggest that response to chromium may be dependent on individual patient phenotypes with those with high insulin resistance being most responsive.49–51
Coenzyme Q10. Coenzyme Q10 is a cofactor used in oxidative respiration and is produced endogenously. Supplementation of coenzyme Q10 is especially popular for cardiovascular diseases. Two RCTs of patients with type 2 diabetes and a single RCT of patients with type 1 diabetes produced no strong evidence for glycemic control with coenzyme Q10 supplementation.52,53
Magnesium. Magnesium is an abundant mineral in the human body involved in numerous biochemical processes, including glucose metabolism. Dietary sources of magnesium include whole grains, beans, nuts, and green, leafy vegetables. Magnesium deficiency is associated with poor glucose control in patients with diabetes.54 However, in clinical trials, supplementation of magnesium has not yielded clear long-term positive benefits in type 2 diabetes.
Song et al.55 conducted a meta-analysis compiling data from nine RCTs with a total of 370 subjects with type 2 diabetes. The duration of the studies ranged from 4 to 16 weeks and the studies administered a median magnesium dose of 15 mmol/day (360 mg/day) to active-treatment groups. The mean post-intervention fasting glucose after 12 weeks of treatment was significantly lower among active-treatment compared to placebo groups: –0.56 mmol/l (95% CI –1.10 to –0.01). The difference in post-intervention A1C was not significant.
Observational data suggest that magnesium supplementation may decrease the risk of type 2 diabetes. A meta-analysis in 200756 included seven prospective cohort studies that collected dietary and supplementary magnesium intake and incidence of type 2 diabetes. The relative risk for the development of type 2 diabetes with a 100 mg/day increase in magnesium was 0.85 (95% CI 0.79–0.92).
Omega-3 fatty acid. Omega-3 polyunsaturated fatty acids (PUFAs) are one of the most common dietary supplements taken in the United States.3 Major sources of omega-3 PUFAs include fish, marine-derived supplements, and prescription formulations (sold under the trade names Omacor and Lovaza).
In the general population, observational studies and RCTs indicate reductions in coronary artery disease and sudden cardiac death based on omega-3 PUFA intake.57,58 In patients with type 2 diabetes, a meta-analysis of omega-3 PUFA supplementation59 that pooled data from 23 RCTs with a total of 1,075 patients did not show any significant changes in fasting glucose, A1C, or fasting insulin.
With a mean intake of 3.5 g/day of omega-3 PUFAs, significant decreases in triglycerides (–0.45 mmol/l, 95% CI –0.58 to –0.32) and VLDL cholesterol (–0.07 mmol/l, 95% CI –0.13 to 0.00) and increases in LDL cholesterol (0.11 mmol/l, 95% CI 0.00–0.22) were noted. Subanalysis of patients with hypertriglyceridemia demonstrated no significant increase in LDL. Based on multiple studies, high omega-3 PUFA intake does not prevent the onset of type 2 diabetes.60
Vanadium. Vanadium is a mineral with no known biological importance or deficiency-associated disease.39,61 Although three controlled studies of vanadium for type 2 diabetes reported significant decreases in fasting blood glucose levels, small sample sizes and lack of randomization limit these results.62–64
A high prevalence of patients with diabetes use CAM therapies, and health care providers need to be prepared to counsel such patients. Frequently, CAM modalities used for diabetes are biologically based therapies and mind-body medicine. Biologically based practices, including herbs and dietary supplements, can affect glucose metabolism, but evidence for their clinical use in patients with diabetes is scarce. Mind-body practices may offer a healthy lifestyle change for patients with diabetes, but long-term improvements in glycemic control have not been shown in clinical trials.
Regulation of botanical products in the United States allows for marketing without established efficacy or safety. Physicians need to specifically ask about supplement use and monitor patients for potential adverse effects, especially hypoglycemia in patients with diabetes.
When counseling patients on CAM use, physicians should respect patients’ choices regarding self-management, while providing evidence-based information about efficacy and safety or the lack thereof. Despite unclear data, a large number of patients will continue using CAM in the future. As research grows in this field, physicians have an opportunity to help patients make decisions about the most safe and effective CAM therapies to consider.