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Cancer-chromium connection?

Chromium has long been viewed as a potential anti-diabetic supplement. But the form of chromium in supplements may not always be the final form your cells get. This study looked at a potential connection to cancer, through testing extremely high dose chromium exposure.

Study under review: Carcinogenic Chromium(VI) Compounds Formed by Intracellular Oxidation of Chromium(III) Dietary Supplements by Adipocytes


There is some evidence[1] that suggests chromium supplementation can lower the fasting plasma glucose level in people with diabetes, although its impact on hemoglobin A1C, a test that reflects longer-term glucose control, is not completely clear. Nor is it clear[2] exactly how it works to lower glucose levels. One of the main hypotheses for chromium’s mechanism involves a small protein fragment (i.e. a peptide) known as chromodulin[3], sometimes called low molecular-weight chromium-binding substance (LMWCr).

As shown in Figure 1, chromodulin is thought to work[4] by binding chromium (hence its name) and amplifying the insulin receptor’s response to insulin, so that the insulin signal causes a stronger response, resulting in greater glucose uptake from the blood. That’s a great story. The only problem with it is that chromodulin may not exist.

Figure 1: How chromodulin is thought to work

Adapted from: Phung et al. Am J Health Syst Pharm. 2010 Apr.

Previous work[5] from the authors of the paper under review suggests that chromodulin may be an artifact of how previous studies, which reported its discovery and isolation, were performed. The authors report that chromium seems to like to bind to all sorts of larger proteins that have some specific sequences. Then, when researchers break apart cells to study what’s binding chromium, they also break apart the proteins that were binding chromium. Thus, what comes out are low-weight bits of protein (peptides) stuck to chromium. So, according to these authors, what people have been calling “chromodulin” all this time isn’t a special peptide. It’s actually just broken-off bits from other, larger proteins that like to stick to chromium.

The good news is that, according to the authors, there’s still a possible mechanism by which chromium could lower blood glucose levels even if chromodulin doesn’t exist. The bad news, according to the authors, is that the very same mechanism may involve a potentially toxic byproduct.

The form of chromium that is normally ingested as a supplement is known as chromium (III) (CrIII). It is considered relatively safe[6]. The Roman numeral “III” refers to chromium’s oxidation state. CrIII is the kind of chromium that you’ll find in most chromium supplements, usually bound to a molecule of picolinate. However, other more oxidized forms of chromium such as CrV[7] and CrVI[8] can cause DNA damage, which could lead to cancer.

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