Chromium deficiency

Chromium deficiency is described as the consequence of an insufficient dietary intake of the mineral chromium. Chromium was first proposed as an essential element for normal glucose metabolism in 1959,^[1] and was widely accepted as being such by the 1990s.^[2] Cases of deficiency were described in people who received all of their nutrition intravenously for long periods of time.^[3]

Chromium deficiency
Chromium
Specialty	Endocrinology

The essentiality of chromium has been challenged.^[4][5][6] Whereas the authorities in the European Union do not recognize chromium as an essential nutrient,^[7] those in the United States do, and identify an adequate intake for adults as between 25 and 45 μg/day, depending on age and sex.^[8] Dietary supplements containing chromium are widely available in the United States, with claims for benefits for fasting plasma glucose, hemoglobin A1C and weight loss. Reviews report the changes as modest, and without scientific consensus that the changes have a clinically relevant impact.^[9][10]

Signs and symptoms

The claimed symptoms of chromium deficiency caused by long-term total parenteral nutrition are severely impaired glucose tolerance, weight loss, peripheral neuropathy and confusion.^[11][8]

Diagnosis

According to the Dietary Reference Intake review, neither plasma nor urine concentrations can serve as useful clinical indicators of chromium status. Before chromium became a standard ingredient in total parenteral nutrition (TPN), people receiving TPN as their sole source of nutrition developed symptoms that were reversed within two weeks of chromium being added.^[8]

Dietary recommendations

The U.S. Institute of Medicine (IOM) updated Estimated Average Requirements (EARs) and Recommended Dietary Allowances (RDAs) for chromium in 2001. For chromium there was not sufficient information to set EARs and RDAs, so needs are described as estimates for Adequate Intakes (AIs). The current AIs for chromium for women ages 14 and up is 25 μg/day up to age 50 and 20 μg/day for older. AI for pregnancy is 30 μg/day. AI for lactation is 45 μg/day. For men ages 14 and up 35 μg/day up to age 50 and 30 μg/day for older. For infants to children ages 1–13 years the AI increases with age from 0.2 to 25 μg/day. As for safety, the IOM sets Tolerable upper intake levels (ULs) for vitamins and minerals when evidence is sufficient. In the case of chromium there is not yet enough information and hence no UL. Collectively the EARs, RDAs, AIs and ULs are referred to as Dietary Reference Intakes (DRIs).^[8]

Japan designate chromium as an essential nutrient, identifying 10 μg/day as an Adequate Intake for adults.^[12]

The European Food Safety Authority (EFSA) refers to the collective set of information as Dietary Reference Values, with Population Reference Intake (PRI) instead of RDA, and Average Requirement instead of EAR. AI and UL defined the same as in United States. The EFSA does not consider chromium to be an essential nutrient, and so has not set PRIs, AIs or ULs. Chromium is the only mineral for which the United States and the European Union disagree on essentiality.^[7][13]

For U.S. food and dietary supplement labeling purposes the amount in a serving is expressed as a percent of Daily Value (%DV). For chromium labeling purposes 100% of the Daily Value was 120 μg, but as of 27 May 2016 it was revised to 35 μg to bring it into agreement with the RDA.^[14][15] Compliance with the updated labeling regulations was required by 1 January 2020, for manufacturers with $10 million or more in annual food sales, and by 1 January 2021 for manufacturers with less than $10 million in annual food sales.^[16][17][18] During the first six months following the 1 January 2020 compliance date, the FDA plans to work cooperatively with manufacturers to meet the new Nutrition Facts label requirements and will not focus on enforcement actions regarding these requirements during that time.^[16] A table of the old and new adult Daily Values is provided at Reference Daily Intake.

Sources

Approximately 2% of ingested chromium(III) is absorbed, with the remainder being excreted in the feces. Amino acids, vitamin C and niacin may enhance the uptake of chromium from the intestinal tract.^[19] After absorption, this metal accumulates in the liver, bone, and spleen. Trivalent chromium is found in a wide range of foods, including whole-grain products, processed meats, high-bran breakfast cereals, coffee, nuts, green beans, broccoli, spices, and some brands of wine and beer.^[19] Most fruits and vegetables and dairy products contain only low amounts.^[3]

Diabetes

Given the evidence for chromium deficiency causing problems with glucose management in the context of intravenous nutrition products formulated without chromium,^[20] research interest turned to whether chromium supplementation for people who have type 2 diabetes but are not chromium deficient could benefit. Looking at the results from four meta-analyses, one reported a statistically significant decrease in fasting plasma glucose levels (FPG) and a non-significant trend in lower hemoglobin A1C (HbA1C).^[21] A second reported the same,^[22] a third reported significant decreases for both measures,^[23] while a fourth reported no benefit for either.^[24] A review published in 2016 listed 53 randomized clinical trials that were included in one or more of six meta-analyses. It concluded that whereas there may be modest decreases in FPG and/or HbA1C that achieve statistical significance in some of these meta-analyses, few of the trials achieved decreases large enough to be expected to be relevant to clinical outcome. The authors also mentioned that trial design was for chromium as an addition to standard glycemic control medications, and so did not evaluate chromium as a first treatment for type 2 diabetes, or for prevention of progression from pre-diabetes to diabetes. The conclusion was that "...there is still little reason to recommend chromium dietary supplements to achieve clinically meaningful improvements in glycemic control."^[9] The American Diabetes Association publishes a standards of care review every year. The 2018 review makes no mention of chromium supplementation as a possible treatment.^[25]

Supplementation

Chromium supplementation in general is subject to a certain amount of controversy as it is by no means clear that chromium is an essential element in human biology.^[26] Nevertheless, chromium is an ingredient in total parenteral nutrition, along with other trace minerals.^[20] It is also in nutritional products for preterm infants.^[27] Many chromium-containing products, including chromium chloride, chromium citrate, chromium(III) picolinate, chromium(III) polynicotinate are sold as non-prescription dietary supplements.^[28]

Government-approved health claims

In 2005, the U.S. Food and Drug Administration approved a Qualified Health Claim for chromium picolinate with a requirement for very specific label wording: "One small study suggests that chromium picolinate may reduce the risk of insulin resistance, and therefore possibly may reduce the risk of type 2 diabetes. FDA concludes, however, that the existence of such a relationship between chromium picolinate and either insulin resistance or type 2 diabetes is highly uncertain."^[29] In 2010, chromium(III) picolinate was approved by Health Canada to be used in dietary supplements. Approved labeling statements included: "...provides support for healthy glucose metabolism."^[30] The European Food Safety Authority (EFSA) approved claims in 2010 that chromium contributed to normal macronutrient metabolism and maintenance of normal blood glucose concentration.^[31]

See also

• Chromium toxicity

References

1. SCHWARZ, K; MERTZ, W (November 1959). "Chromium(III) and the glucose tolerance factor". Archives of Biochemistry and Biophysics. 85: 292–295. doi:10.1016/0003-9861(59)90479-5. PMID 14444068.
2. Mertz, W (April 1993). "Chromium in human nutrition: a review". The Journal of Nutrition. 123 (4): 626–633. doi:10.1093/jn/123.4.626. PMID 8463863.
3. Expert group on Vitamins and Minerals (August 2002). (PDF). Archived from the original (PDF) on 7 February 2012. Retrieved 24 February 2013.
4. Vincent, John B. (2010). "Chromium: celebrating 50 years as an essential element?". Dalton Transactions. 39 (16): 3787–3794. doi:10.1039/B920480F. PMID 20372701.
5. Jeejeebhoy, Khursheed N. (1999). "The role of chromium in nutrition and therapeutics and as a potential toxin". Nutrition Reviews. 57 (11): 329–335. doi:10.1111/j.1753-4887.1999.tb06909.x. PMID 10628183.
6. Vincent, JB (2013). "Chromium: Is It Essential, Pharmacologically Relevant, or Toxic?". Interrelations between Essential Metal Ions and Human Diseases. Metal Ions in Life Sciences. Vol. 13. pp. 171–198. doi:10.1007/978-94-007-7500-8_6. ISBN 978-94-007-7499-5. PMID 24470092.
7. "Overview on Dietary Reference Values for the EU population as derived by the EFSA Panel on Dietetic Products, Nutrition and Allergies" (PDF). 2017.
8. Chromium. IN: Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Chromium, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Chromium National Academy Press. 2001, pp. 197-223.
9. Costello RB, Dwyer JT, Bailey RL (2016). "Chromium supplements for glycemic control in type 2 diabetes: limited evidence of effectiveness". Nutr. Rev. 74 (7): 455–468. doi:10.1093/nutrit/nuw011. PMC 5009459. PMID 27261273.
10. Onakpoya I, Posadzki P, Ernst E (2013). "Chromium supplementation in overweight and obesity: a systematic review and meta-analysis of randomized clinical trials". Obes Rev. 14 (6): 496–507. doi:10.1111/obr.12026. PMID 23495911. S2CID 21832321.
11. Freund, Herbert; Atamian, Susan; Fischer, Josef E. (February 1979). "Chromium deficiency during total parenteral nutrition". JAMA. 241 (5): 496–498. doi:10.1001/jama.1979.03290310036012. PMID 104057.
12. Overview of Dietary Reference Intakes for Japanese (2015)
13. Tolerable Upper Intake Levels For Vitamins And Minerals (PDF), European Food Safety Authority, 2006
14. "Federal Register May 27, 2016 Food Labeling: Revision of the Nutrition and Supplement Facts Labels. FR page 33982" (PDF).
15. . Dietary Supplement Label Database (DSLD). Archived from the original on 7 April 2020. Retrieved 16 May 2020.
16. "FDA provides information about dual columns on Nutrition Facts label". U.S. Food and Drug Administration (FDA). 30 December 2019. Retrieved 16 May 2020.   This article incorporates text from this source, which is in the public domain.
17. "Changes to the Nutrition Facts Label". U.S. Food and Drug Administration (FDA). 27 May 2016. Retrieved 16 May 2020.   This article incorporates text from this source, which is in the public domain.
18. "Industry Resources on the Changes to the Nutrition Facts Label". U.S. Food and Drug Administration (FDA). 21 December 2018. Retrieved 16 May 2020.   This article incorporates text from this source, which is in the public domain.
19. Lukaski, Henry C. (1999). "Chromium as a supplement". Annual Review of Nutrition. 19 (1): 279–302. doi:10.1146/annurev.nutr.19.1.279. PMID 10448525.
20. Stehle P, Stoffel-Wagner B, Kuhn KS (2016). "Parenteral trace element provision: recent clinical research and practical conclusions". Eur J Clin Nutr. 70 (8): 886–893. doi:10.1038/ejcn.2016.53. PMC 5399133. PMID 27049031.
21. San Mauro-Martin I, Ruiz-León AM, et al. (2016). "[Chromium supplementation in patients with type 2 diabetes and high risk of type 2 diabetes: a meta-analysis of randomized controlled trials]". Nutr Hosp (in Spanish). 33 (1): 27. doi:10.20960/nh.27. PMID 27019254.
22. Abdollahi M, Farshchi A, Nikfar S, Seyedifar M (2013). "Effect of chromium on glucose and lipid profiles in patients with type 2 diabetes; a meta-analysis review of randomized trials". J Pharm Pharm Sci. 16 (1): 99–114. doi:10.18433/j3g022. PMID 23683609.
23. Suksomboon N, Poolsup N, Yuwanakorn A (2014). "Systematic review and meta-analysis of the efficacy and safety of chromium supplementation in diabetes". J Clin Pharm Ther. 39 (3): 292–306. doi:10.1111/jcpt.12147. PMID 24635480. S2CID 22326435.
24. Bailey CH (January 2014). "Improved meta-analytic methods show no effect of chromium supplements on fasting glucose". Biol Trace Elem Res. 157 (1): 1–8. doi:10.1007/s12011-013-9863-9. PMID 24293356. S2CID 2441511.
25. Standards of Medical Care for Diabetes - 2018 Diabetes Care 2008:41:Supplement 1.
26. Maret, Wolfgang (2019). "Chapter 9. Chromium Supplementation in Human Health, Metabolic Syndrome, and Diabetes". In Sigel, Astrid; Freisinger, Eva; Sigel, Roland K. O.; Carver, Peggy L. (Guest editor) (eds.). Essential Metals in Medicine:Therapeutic Use and Toxicity of Metal Ions in the Clinic. Vol. 19. Berlin: de Gruyter GmbH. pp. 231–251. doi:10.1515/9783110527872-015. ISBN 978-3-11-052691-2. PMID 30855110. {{cite book}}: |editor4-first= has generic name (help); |journal= ignored (help)
27. Finch, C. W (2015). "Review of trace mineral requirements for preterm infants: What are the current recommendations for clinical practice?". Nutrition in Clinical Practice. 30 (1): 44–58. CiteSeerX 10.1.1.957.4763. doi:10.1177/0884533614563353. PMID 25527182.
28. "Chromium". Office of Dietary Supplements, US National Institutes of Health. 2016. Retrieved 26 June 2016.
29. FDA Qualified Health Claims: Letters of Enforcement Discretion, Letters of Denial U.S. Food and Drug Administration, Docket #2004Q-0144 (August 2005).
30. "Monograph: Chromium (from Chromium picolinate)". Health Canada. 9 December 2009. Retrieved 24 March 2015.
31. Scientific Opinion on the substantiation of health claims related to chromium and contribution to normal macronutrient metabolism (ID 260, 401, 4665, 4666, 4667), maintenance of normal blood glucose concentrations (ID 262, 4667), contribution to the maintenance or achievement of a normal body weight (ID 339, 4665, 4666), and reduction of tiredness and fatigue (ID 261) pursuant to Article 13(1) of Regulation (EC) No 1924/2006 21 April 2020 at the Wayback Machine European Food Safety Authority EFSA J 2010;8(10)1732.

Further reading

• A "possible resolution of controversies in chromium biology" is suggested by Wolfgang Maret in chapter 9, pp 246–248 of Essential Metals in Medicine: Therapeutic Use and Toxicity of Metal Ions in the Clinic. edited by Astrid Sigel, Eva Freisinger, Roland K. O. Sigel and Peggy L. Carver; de Gruyter GmbH (publisher), 2019 Berlin.
• "Dietary Supplement Fact Sheet: Chromium". Office of Dietary Supplements, National Institutes of Health. Retrieved 24 February 2013.
• Chromium in glucose metabolism

External links