Chromium deficiency: Difference between revisions

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| caption = [[Chromium]]

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'''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,<ref>{{cite journal|last1=SCHWARZ|first1=K|last2=MERTZ|first2=W|title=Chromium(III) and the glucose tolerance factor.|journal=Archives of Biochemistry and Biophysics|date=November 1959|volume=85|pages=292–295|pmid=14444068|doi=10.1016/0003-9861(59)90479-5}}</ref> and was widelybut acceptedits asbiological beingfunction suchhas bynot thebeen 1990sidentified.<ref>{{cite journal|last1=Mertz|first1=W|title=Chromium in human nutrition: a review.|journal=The Journal of Nutrition|date=April 1993|volume=123|issue=4|pages=626–633|pmid=8463863|doi=10.1093/jn/123.4.626|doi-access=free}}</ref> Cases of deficiency were described in people who [[Parenteral nutrition|received all of their nutrition intravenously]] for long periods of time.<ref name=Expert>{{cite web|title=Review of Chromium |date=August 2002 |url=http://www.food.gov.uk/multimedia/pdfs/reviewofchrome.pdf |accessdate=24 February 2013 |author=Expert group on Vitamins and Minerals |url-status=dead |archiveurlarchive-url=https://web.archive.org/web/20120207123911/http://www.food.gov.uk/multimedia/pdfs/reviewofchrome.pdf |archivedatearchive-date=7 February 2012 }}</ref>

The essentiality of chromium has been challenged.<ref name=Vincent>{{cite journal|last=Vincent|first=John B.|title=Chromium: celebrating 50 years as an essential element?|journal=Dalton Transactions|year=2010|volume=39|issue=16|pages=3787–3794|doi=10.1039/B920480F|pmid=20372701}}</ref><ref>{{cite journal |doi=10.1111/j.1753-4887.1999.tb06909.x |last=Jeejeebhoy |first=Khursheed N. |title=The role of chromium in nutrition and therapeutics and as a potential toxin |journal=Nutrition Reviews |volume=57 |issue=11 |pages=329–335 |year=1999 |pmid=10628183|doi-access=free }}</ref><ref name=Vincent2>{{cite book|last1=Vincent|first1=JB|titlechapter=InterrelationsChromium: betweenIs It Essential, MetalPharmacologically IonsRelevant, andor HumanToxic? Diseases|chaptertitle=Chromium:Interrelations isbetween itEssential essential,Metal pharmacologicallyIons relevant,and orHuman toxic?Diseases|year=2013|volume=13|pages=171–198|pmid=24470092|doi=10.1007/978-94-007-7500-8_6|isbn=978-94-007-7499-5|series=Metal Ions in Life Sciences}}</ref> Whereas the authorities in the European Union do not recognize chromium as an essential nutrient,<ref name="EFSA" /> 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.<ref name=ChromiumDRI/> [[Dietary supplement]]s 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.<ref name=Costello2016/><ref name=Onakpoya2013>{{cite journal |vauthors=Onakpoya I, Posadzki P, Ernst E |title=Chromium supplementation in overweight and obesity: a systematic review and meta-analysis of randomized clinical trials |journal=Obes Rev |volume=14 |issue=6 |pages=496–507 |date=2013 |pmid=23495911 |doi=10.1111/obr.12026 |urls2cid=21832321 }}</ref>

The claimed symptoms of chromium deficiency caused by long-term [[total parenteral nutrition]] are severely [[impaired glucose tolerance]], weight loss, peripheral neuropathy and confusion.<ref name=Freund>{{cite journal |last=Freund |first=Herbert |author2=Atamian, Susan |author3=Fischer, Josef E. |title=Chromium deficiency during total parenteral nutrition |journal=JAMA |volume=241 |issue=5 |pages=496–498 |date=February 1979 |pmid=104057 |doi=10.1001/jama.1979.03290310036012}}</ref><ref name=ChromiumDRI/>

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 gettingreceiving TPN as their sole source of nutrition developed symptoms that were reversed within two weekweeks afterof chromium wasbeing added.<ref name=ChromiumDRI/>

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 level]]s (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 Intake]]s (DRIs).<ref name=ChromiumDRI>Chromium. IN: [https://www.ncbi.nlm.nih.gov/books/NBK222329/ 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, PPpp. 197-223.</ref>

Japan designatedesignates chromium as an essential nutrient, identifying 10 μg/day as an Adequateadequate Intakeintake for adults.<ref name=Japan>[http://www.mhlw.go.jp/file/06-Seisakujouhou-10900000-Kenkoukyoku/Overview.pdf Overview of Dietary Reference Intakes for Japanese (2015)]</ref>

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 of27 May 27, 2016 it was revised to 35 μg to bring it into agreement with the RDA.<ref name="FedReg">{{cite web|url=https://www.gpo.gov/fdsys/pkg/FR-2016-05-27/pdf/2016-11867.pdf |title=Federal Register May 27, 2016 Food Labeling: Revision of the Nutrition and Supplement Facts Labels. FR page 33982.}}</ref><ref>{{cite web | title=Daily Value Reference of the Dietary Supplement Label Database (DSLD) | website=Dietary Supplement Label Database (DSLD) | url=https://www.dsld.nlm.nih.gov/dsld/dailyvalue.jsp | access-date=16 May 2020 | archive-date=7 April 2020 | archive-url=https://web.archive.org/web/20200407073956/https://dsld.nlm.nih.gov/dsld/dailyvalue.jsp | url-status=dead }}</ref> 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.<ref name="FDA nutrition label">{{cite web | title=FDA provides information about dual columns on Nutrition Facts label | website=U.S. [[Food and Drug Administration]] (FDA) | date=30 December 2019 | url=https://www.fda.gov/news-events/fda-brief/fda-brief-fda-provides-additional-information-about-requirements-dual-column-labeling-serving-sizes | access-date=16 May 2020}} {{PD-notice}}</ref><ref name="FDAdelay">{{cite web | title=Changes to the Nutrition Facts Label | website=U.S. [[Food and Drug Administration]] (FDA) | date=27 May 2016 | url=https://www.fda.gov/food/food-labeling-nutrition/changes-nutrition-facts-label | access-date=16 May 2020}} {{PD-notice}}</ref><ref>{{cite web | title=Industry Resources on the Changes to the Nutrition Facts Label | website=U.S. [[Food and Drug Administration]] (FDA) | date=21 December 2018 | url=https://www.fda.gov/food/food-labeling-nutrition/industry-resources-changes-nutrition-facts-label | access-date=16 May 2020}} {{PD-notice}}</ref> 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.<ref name="FDA nutrition label" /> A table of the old and new adult Daily Values is provided at [[Reference Daily Intake]].

Approximately 2% of ingested chromium(III) is absorbed, with the remainder being excreted in the feces. Amino acids, [[vitamin C]] and [[Niacin (substance)|niacin]] may enhance the uptake of chromium from the intestinal tract.<ref name=Lukaski>{{cite journal |last=Lukaski |first=Henry C.|title=Chromium as a supplement |journal=Annual Review of Nutrition |volume=19 |issue=1 |pages=279–302 |year=1999 |pmid=10448525 |doi=10.1146/annurev.nutr.19.1.279}}</ref> 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 bean|green beans]], [[broccoli]], [[Spice|spices]], and some brands of wine and beer.<ref name=Lukaski/> Most fruits and vegetables and dairy products contain only low amounts.<ref name=Expert/>

GivenLittle thestrong evidence forexists chromium deficiency causing problems with glucose management in the context of intravenous nutrition products formulated without chromium,<ref name=Stehle2016>{{cite journal |vauthors=Stehle P, Stoffel-Wagner B, Kuhn KS |title=Parenteral trace element provision: recent clinical research and practical conclusions |journal=Eur J Clin Nutr |volume=70 |issue=8 |pages=886–893 |date=2016 |pmid=27049031 |pmc=5399133 |doi=10.1038/ejcn.2016.53 |url=}}</ref> research interest turned to whetherthat chromium supplementation forbenefits people who have type 2 diabetes but are not chromium deficient could benefit. Looking at the results from fourOne meta-analyses, oneanalysis reported a statistically significant decrease in fasting [[plasma glucose]] levels (FPG) and a non-significant trend in lower [[Glycated hemoglobin|hemoglobin A1C]] (HbA1C).<ref name=Mauro2016>{{cite journal |vauthors=San Mauro-Martin I, Ruiz-León AM, et al.|title=[Chromium supplementation in patients with type 2 diabetes and high risk of type 2 diabetes: a meta-analysis of randomized controlled trials] |language=Spanishes|journal=Nutr Hosp |volume=33 |issue=1 |pages=27 |date=2016 |pmid=27019254 |doi= 10.20960/nh.27|url=|doi-access=free |url=https://www.redalyc.org/pdf/3092/309245772026.pdf }}</ref> A second reported the same,<ref name=Abdoll2013>{{cite journal |vauthors=Abdollahi M, Farshchi A, Nikfar S, Seyedifar M |title=Effect of chromium on glucose and lipid profiles in patients with type 2 diabetes; a meta-analysis review of randomized trials |journal=J Pharm Pharm Sci |volume=16 |issue=1 |pages=99–114 |date=2013 |pmid=23683609 |doi= 10.18433/j3g022|url=|doi-access=free |url=http://pdfs.semanticscholar.org/40c6/0770c72b2d49c52548eef13cf3b4e2f031ea.pdf }}</ref>, a third reported significant decreases for both measures,<ref name=Suk2014>{{cite journal |vauthors=Suksomboon N, Poolsup N, Yuwanakorn A |title=Systematic review and meta-analysis of the efficacy and safety of chromium supplementation in diabetes |journal=J Clin Pharm Ther |volume=39 |issue=3 |pages=292–306 |date=2014 |pmid=24635480 |doi=10.1111/jcpt.12147 |urls2cid=22326435 |doi-access=free }}</ref> while a fourth reported no benefit for either.<ref>{{cite journal |vauthors=Bailey CH |title=Improved meta-analytic methods show no effect of chromium supplements on fasting glucose |journal=Biol Trace Elem Res |volume=157 |issue=1 |pages=1–8 |date=January 2014 |pmid=24293356 |doi=10.1007/s12011-013-9863-9 |urls2cid=2441511 }}</ref> A review published in 2016 listed 53 [[randomized clinical trial]]s that were included in one or more of six [[meta-analysis|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."<ref name=Costello2016>{{cite journal |vauthors=Costello RB, Dwyer JT, Bailey RL |title=Chromium supplements for glycemic control in type 2 diabetes: limited evidence of effectiveness |journal=Nutr. Rev. |volume=74 |issue=7 |pages=455–468 |date=2016 |pmid=27261273 |doi=10.1093/nutrit/nuw011 |url=|pmc=5009459 }}</ref> 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.<ref>[https://diabetesed.net/wp-content/uploads/2017/12/2018-ADA-Standards-of-Care.pdf Standards of Medical Care for Diabetes - 2018] Diabetes Care 2008:41:Supplement 1.</ref>

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.<ref>{{cite book |last1=Maret|first1=Wolfgang |editor1-last=Sigel|editor1-first=Astrid|editor2-last=Freisinger|editor2-first=Eva|editor3-last=Sigel|editor3-first=Roland K. O. |editor4-last=Carver|editor4-first=Peggy L. (Guest editor) |title=Essential Metals in Medicine:Therapeutic Use and Toxicity of Metal Ions in the Clinic|journal=Metal Ions in Life Sciences |volume=19 |date=2019 |publisher=de Gruyter GmbH|location=Berlin|isbn=978-3-11-052691-2|doi=10.1515/9783110527872-015|pmid=30855110|pages=231–251|chapter=Chapter 9. Chromium Supplementation in Human Health, Metabolic Syndrome, and Diabetes}}</ref> Nevertheless, chromium is an ingredient in [[total parenteral nutrition]], along with other trace minerals.<ref name=Stehle2016>{{cite journal |vauthors=Stehle P, Stoffel-Wagner B, Kuhn KS |title=Parenteral trace element provision: recent clinical research and practical conclusions |journal=Eur J Clin Nutr |volume=70 |issue=8 |pages=886–893 |date=2016 |pmid=27049031 |pmc=5399133 |doi=10.1038/ejcn.2016.53 }}</ref> It is also in nutritional products for [[preterm infant]]s.<ref>{{cite journal|pmid=25527182|year=2015|last1=Finch|first1=C. W|title=Review of trace mineral requirements for preterm infants: What are the current recommendations for clinical practice?|journal=Nutrition in Clinical Practice|volume=30|issue=1|pages=44–58|doi=10.1177/0884533614563353|citeseerx=10.1.1.957.4763}}</ref> Many chromium-containing products, including [[chromium chloride]], [[chromium citrate]], [[chromium(III) picolinate]], [[Chromium polynicotinate|chromium(III) polynicotinate]] are sold as non-prescription dietary supplements.<ref name=ods>{{cite web | url=https://ods.od.nih.gov/factsheets/Chromium-HealthProfessional/#h2 | title=Chromium | publisher=Office of Dietary Supplements, US National Institutes of Health | date=2016 | accessdate=26 June 2016}}</ref>

==== 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."<ref>[https://wayback.archive-it.org/7993/20171114183739/https://www.fda.gov/Food/IngredientsPackagingLabeling/LabelingNutrition/ucm073017.htm FDA Qualified Health Claims: Letters of Enforcement Discretion, Letters of Denial] U.S. Food and Drug Administration, Docket #2004Q-0144 (August 2005).</ref> 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."<ref>{{cite web |url=http://webprod.hc-sc.gc.ca/nhpid-bdipsn/monoReq.do?id=65 |title=Monograph: Chromium (from Chromium picolinate) |publisher=Health Canada |date =9December 9, 2009 |accessdate =24 March 24, 2015}}</ref> The [[European Food Safety Authority]] (EFSA) approved claims in 2010 that chromium contributed to normal macronutrient metabolism and maintenance of normal blood glucose concentration.<ref name=EFSA2010>[https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2010.1732 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] {{Webarchive|url=https://web.archive.org/web/20200421163705/https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2010.1732 |date=21 April 2020 }} European Food Safety Authority EFSA J 2010;8(10)1732.</ref>

*A "possible resolution of controversies in chromium biology" is suggested by Wolfgang Maret in chapter 9, pp 246-248246–248of<I>''Essential Metals in Medicine: Therapeutic Use and Toxicity of Metal Ions in the Clinic. </I>'' edited by Astrid Sigel, Eva Freisinger, Roland K. O. Sigel and Peggy L. Carver; de Gruyter GmbH (publisher), 2019 Berlin.

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