Headlines across the country recently were defaming nutritional supplements containing trivalent chromium (Cr(III)), claiming it to be a “sleeper cell” that’s capable of turning into its “cancerous cousin” Hexavalent Chromium (Cr(VI)) within the body, this is based on a hypothesis unveiled in a study testing a prospective anti-diabetic drug; tri-nuclear chromium propionate.
Cr(VI) is more widely known as the villain element in the Erin Brockovich film, which was a true-events inspired story of contaminated water supplies making farmers sick in the US farming town of Hinkley in California. Cr(VI) is a by-product of industrial processes, whereas in contrast, Cr(III) is a trace element that is essential to normal human glucose, protein, and fat metabolism.
This study, which was a collaborative work by the University of Sydney and UNSW, and published in the journal Angewandte Chemie lists this as a hypothesis warranting further investigations.
The study determined these findings by injecting animal fat cells (adipocytes) directly with Cr(III) in a laboratory (in-vitro) and then observed the chemical elements formed by a powerful X-ray. They then classified whether those elements were the carcinogenic forms of Chromium - namely Cr(VI). The researchers observed that oxidation processes occurred within the cell, and formed the carcinogenic forms of chromium - Cr(VI). Therefore they drew the conclusion that because oxidative processes may occur in the blood as were observed in the experimental “living cell”, this raises a concern over the safety of oral chromium supplementation since these mechanisms (oxidation) may occur in a similar manner.
The study then goes on to conclude that;
“Although animal experiments have yet to provide conclusive evidence for Cr(III) carcinogenicity, these studies cannot be extrapolated to human exposure because of the long latency time of chromium-induced cancer in humans, and the long-term exposure of patients with diabetes to the oxidative stress that facilitates Chromium oxidation in both the blood and cells. Animal studies that mimic long-term oxidative stress have yet to be conducted. In light of these findings, there is a need for epidemiological studies to ascertain whether Cr(III) supplements alter cancer risk."
Complementary Medicines Australia (CMA) chief executive officer, Mr Carl Gibson, highlighted that the study looked at the injection of Cr(III) directly into mice fat cells, this does not take into account the physiological mechanisms of chromium handling by the body.
“There are many biochemical processes that take place in human nutrition, and the transport of nutrients around the body to active sites, including excretion or storage, was not included in the researchers’ methodology”
-Carl Gibson, CMA
This isn't the first study to highlight the carcinogenicity potential of chromium supplementation. Published by the National Toxicity Program was a three month and two year rat and mice study of chromium picolinate monohydrate exposure in feed. Despite massive doses, equivalent of between 6mg and up to 6 grams per kilogram of body weight, this study concluded that only the male rats showed an increased incidence of preputial gland adenomas after 2 years. Given that the supplemental use of chromium is limited to microgram dosages in Australia, this amount to induce mutigenicity is not in the same order of magnitude.
To put this into perspective, according to the Environmental Protection Agency; “the general population is exposed to chromium (generally chromium [III]) by eating food, drinking water, and inhaling air that contains the chemical. The average daily intake from air, water, and food is estimated to be less than 0.2 to 0.4 micrograms”. Furthermore both the Complementary Medicines Evaluation Committee (CMEC) - who assess the safety of nutrients for inclusion into the Australian Register of Therapeutic Goods (ARTG) for the Therapeutic Goods Association (TGA) and the European Food Standards Authority (EFSA) have all repeatedly assessed the safety of chromium for inclusion in supplements and determined that up to 250mcg per day permitted in supplementation is safe.[5,6,7]
The CMA prepared the following summary for industry on their key findings regarding the study:
- This study was conducted on mice fat cells (in vitro) only and not the effects that take place in a living organism (in vivo). Hence no meaningful extrapolation into clinical practice can be made without further epidemiological studies.
- The potential genotoxicity of chromium III has been assessed in several in vitro studies. The results are conflicting, with some studies indicating that high concentrations of chromium (III) in the cell could lead to DNA damage.
- However, chromium III compounds do not have genotoxicity activity in vivo. Scientific opinion on the long term safety of chromium establishes that no credible data or reports have shown adverse effects in humans from its consumption, and animal data also suggests that orally administered chromium is safe2 .
- There are a number of biological processes that take place in human digestion and nutrient transport around the body that these researchers have bypassed in their methodology.
- The safety of chromium III is supported by evaluations from international authorities including the European Food Standards Authority (EFSA) and World Health Organisation (WHO).
- The safety of intake levels of up to 250 μg/day for supplemental intake is supported by thorough evaluations from the EFSA and the WHO.
- Human clinical trials have provided strong support for the safety of chromium supplements in chromium picolinate form at levels of up to 1,000 μg per day.
- In 2014 the Council for responsible Nutrition (CRN) concluded that the available clinical trial data was sufficient to indicate safety for chromium supplementation at levels of up to 1,000 μg per day for adults
Australian therapeutic considerations
- Chromium is widely used in listed complementary medicines for a range of therapeutic benefits such as assisting with the symptoms around metabolic disorders, such as insulin resistance and type 2 diabetes.
- The Therapeutic Goods Administration (TGA) restricts chromium supplementation in listed medicines in the form of chromium nicotinate, chromium picolinate and yeast - high chromium to the maximum recommended daily dose of no more than 50μg of chromium for all dosage forms.
- US Environmental Protection Agency. Chromium Compounds Hazard Summary. Revised 2000. [Link]
- National Toxicology Program. NTP toxicology and carcinogenesis studies of chromium picolinate monohydrate (CAS No. 27882-76-4) in F344/N rats and B6C3F1 mice (feed studies). Natl Toxicol Program Tech Rep Ser. 2010 Jun;(556):1-194. [Abstract]
- Wu LE, Levina A, Harris, et al. Carcinogenic Chromium(VI) Compounds Formed by Intracellular Oxidation of Chromium (III) Dietary Supplements by Adipocytes. Angew. Chem. Int. Ed. 2016;55(5):1742-1745 [Abstract]
- Complementary Medicines Australia (CMA) Media Release: Inconclusive study on chromium causes consumer alarm. 2016, Jan 11. [Link]
- Complementary Medicine Evaluation Committee 41st Meeting (CMEC41). Item 7.3 Safety Review of Chromium Picolinate as a Nutritional Supplement. 2003, Aug 1. p.10-12. [Link]
- European Food Safety Authority (EFSA). Scientific Opinion on the safety of trivalent chromium as a nutrient added for nutritional purposes to foodstuffs for particular nutritional uses and foods intended for the general population (including food supplements). EFSA Journal 2010;8(12):1882 [Full Text]
- Complementary Medicines Australia (CMA) Member Alert. Media Watch – Inconclusive study on chromium causes consumer alarm. [Link]