Clinical evidence for chromium supplementation

Several animal studies and a case report in humans have shown that absence of chromium in the diet leads to diabetes, and that the chromium deficit is associated with insulin resistance. So how about the effectiveness of chromium supplementation in patients with type 2 diabetes? Efficacy of chromium to improve glycemic control has not been established.

Anderson et al.[1], have performed a trial that can be considered as the landmark trial of chromium-intervention studies in patients with T2DM. In a randomized controlled trial performed in Chinese patients (a trial published in 1997), a first tentative conclusion about the effects of chromium on glycemic control was given. Chromium picolinate supplements were given over a period of four months to a group of 180 Chinese patients with T2DM. The patients were randomized into three groups, placebo, 200 μg chromium, and 1000 μg of chromium daily as chromium picolinate. After four months, the HbA1c in the placebo group was unchanged (8.5%), while the HbA1c in the 200 μg group showed a significant decrease from 8.5% to 7.5%. In the group treated with 1000 μg chromium a decrease in the HbA1c from 8.5% to 6.6% was seen.

In 2007, Balk et al., performed a systematic review of randomized controlled trials concerning chromium supplementation in T2DM[2]. They found 11 studies with 14 different chromium-based interventions measuring HbA1c as an endpoint. 11 out of 14 found no effect or non-significant effects of chromium supplementation. However, when performing a meta-analysis of these trials (including the study of Anderson et al.), the overall effect of chromium supplementation in people with diabetes was statistically significant in favor of chromium supplementation (-0.6% [95% confidence interval (CI): -0.9 to -0.2]). This mean -0.6% benefit however is largely due to the results of the study of Anderson et al. When excluding this study the effect of chromium on HbA1c is -0.3% [95% CI: -0.5 to -0.1]. When stratifying the pooled results regarding methodological quality, sponsor involvement and western vs. non-western studies, the effects of chromium supplementation turned out to be absent or non-relevant when studies were either of good methodological quality, or were without involvement of industry or were performed in western patients.

Since the review of Balk, two other double-blind, placebo-controlled randomized trials have been published. The first is a 6-month, double-blind study, performed in The Netherlands[3]. After 6 months the effect of chromium supplementation compared to placebo on HbA1c was +0.24 [95% CI: -0.06 to 0.54]. The second study was a trial in which 30 Taiwanese patients with T2DM were enrolled[4]. The patients were divided into three groups: a group which received placebo, a group that received 1000 microgram of chromium (chromium yeast) and a group that received 1000 microgram of chromium together with vitamin C and vitamin E. HbA1c levels dropped from 10.2% (standard deviation (SD) 0.5) to 9.5% (SD 0.2), which was a significant reduction. Unfortunately no between-group analyses (compared to placebo) were performed.

Discussion

There is, as discussed, a well-established role for trivalent chromium in glucose metabolism. However, especially, in western patient with T2DM, this does not mean that supplementation of chromium in de forms and dosages as commonly used in studies lead to (relevant) effects on HbA1c. Question that arise are amongst many others:

  1. Are there patients, who are chromium deficient, and if so
  2. Can they somehow be selected, and if so
  3. Is chromium supplementation beneficial in these patients?
  4. And which forms of chromium in which dosages should be used?

It is of course of interest, that there are a few studies in non-western patients, which did find significant and clinically relevant effects of chromium supplementation on HbA1c. And of course it would be interesting tot see these results replicated in methodologically sound trails. But, except for methodological issues, one could speculate about reasons for the differences in results between western and non-western patients, like genetic differences, but also the possible differences in intake of chromium with a low intake possibly leading to chromium deficiency, or the differences dosages needed to be able to reach clinically meaningful effects in different patient populations.

Unfortunately, a reliable method for assessment of the chromium status is lacking as is sufficient information regarding the bioavailability of different forms of chromium. Future chromium research should focus on establishing a method for assessment of the chromium status. In addition, the bioavailability of different forms of chromium in Western patients (compared to non-Western patients) should be investigated to be able to properly define a potentially effective dose.

Efficacy of chromium to improve glycemic control has not been established. Furthermore, there were some safety concerns with one form of chromium: chromium picolinate and long-term safety has never been established. Last but not least, we should remember that patients with T2DM are not treated in order to lower HbA1c, but to improve the risk these patients have on microvascular and macrovascular complications (and to improve quality of life). At this moment, there are many non-pharmacological and pharmacological interventions possible in T2DM patients known that reduce these risks. So, in the meantime, chromium should not be a treatment option in patients with T2DM and non-pharmacological focus by diabetes health care providers together with patients should be on the items like quitting smoking, maximizing alcohol intake, increase physical exercise, reduce weight, restrict sodium intake and on improving food composition.

References

  1. ^ Anderson RA, Cheng N, Bryden NA, Polansky MM, Chi J, Feng J. Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes. Diabetes 1997;46(11)1786-91.

  2. ^ Balk EM, Tatsioni A, Lichtenstein AH, Lau J, Pittas AG. Effect of chromium supplementation on glucose metabolism and a systematic review of randomized controlled trials. Diabetes Care. 2007;30(8)2154-63.

  3. ^ Kleefstra N, Houweling ST, Bakker SJ, Verhoeven S, Gans RO, Meyboom-de Jong B, Bilo HJ. Chromium treatment has no effect in patients with type 2 diabetes in a Western a randomized, double-blind, placebo-controlled trial. Diabetes Care. 2007;30(5):1092-6.

  4. ^ Albarracin C, Fuqua B, Geohas J, Juturu V, Finch MR, Komorowski JR. Combination of chromium and biotin improves coronary risk factors in hypercholesterolemic type 2 diabetes a placebo-controlled, double-blind randomized clinical trial. J Cardiometab Syndr. 2007;2(2):91-7.

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