890 LETTERS TO THE EDITOR

including improved overall antenatal care. Decisive commu- Chromium supplementation and iron
nity involvement is pivotal. An example of what I propose for
metabolism
women of childbearing age will clarify the following con-
cept: most menstruating women and adolescent girls need to
absorb 1 .4 mg Fe/d, but 20-30% require > 2 mg Fe/d to Dear Sir:

prevent iron deficiency. Iron absorption from poor-quality

The recent report by Lukaski et at ( 1) regarding the effects
diets averages 1.0-l.3 mg/d, which explains why only a
of chromium supplementation in resistance-trained young
few women of childbearing age have adequate iron reserves.
men describes a trend (P = 0. 1 7) toward reduced transferrmn
If menstruating women motivated by active education and
saturation in those receiving supplemental chromium. The
community organizations (eg, schools, churches, market
authors state that “Because chromium competes with iron
places, mothers’ clubs, and factories) ingested a 60-mg for binding on transfernin, it is plausible that the significant
tablet containing iron and folate every week and 10% of the increase in serum chromium concentration seen with chro-
iron was absorbed, their average total iron absorption would mium supplementation, particularly as chromium picolinate,
be brought to I .9-2.2 mg/d. Iron deficiency would be elim-

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adversely affects iron transport and distribution.” They then
mated, iron reserves would slowly build up, and antenatal cite a paper in which chronic parenteral administration of
folate nutrition would also be improved. Upon becoming trivalent chromium to rats diminished various indexes of
pregnant, women would double the weekly dose and would iron status (2).
later continue with the single dose throughout lactation. In fact, serum concentrations of chromium, even when in-
Weekly vitamin A could complement iron where needed. creased by supplementation, are far too low to effectively
Under these conditions, antenatal iron supplementation compete with iron for binding to transferrin. Serum chromium
would become very effective because by entering pregnancy concentration in diabetics receiving 200 ag Cn/d as chromium
with adequate iron reserves, the extra dietary iron needs picolinate was determined to average 16 nmollL after 8 wk (3);
during pregnancy are markedly reduced. this is very similar to the 19 nmolIL measured after comparable
supplementation in Lukaski et al’s study. In contrast, the total-
Fernando E Viteni
iron-binding capacity (TIBC) of serum-which is primarily
indicative of transferrmn capacity-is normally “45-65
molIL (4); it averaged 59 .amolIL at baseline in Lukaski et
Department of Nutritional Sciences
al’s study (and increased during exercise training-notwith-
Morgan Hall
standing the misstatement in the abstract). Clearly, if every
University of California
atom of chromium in the serum were bound to transfemn, it
Berkeley, CA 94720
would have an undetectably small effect on either TIBC or
transferrmn’s saturation. The cited rat study entailed daily ad-
ministration of 1 mg Cr/kg intraperitoneally for 45 consecutive
REFERENCES days. This dose is more than four orders of magnitude greater
than the amount of chromium absorbed from nutritional intakes
I . Ridwan E, Schultink W, Dillon D, Gross R. Effects of weekly iron
of this mineral-and yet it reduced transfemn saturation by
supplementation on pregnant Indonesian women are similar to those of
only 11%!
daily supplementation. Am J Clin Nutr 1996:63:884-90.
If the trend toward reduced transfernin saturation reported
2. Yip R. Iron supplementation during pregnancy: is it effective? Am I
by Lukaski et at is a genuine, confirmable effect, it is more
Clin Nutr l996;63:853-5.
likely to reflect the essential physiologic role of chromium
3. Liu XN, Yang W, Zhang I, et al. Weekly iron supplementation is
effective and safe in pregnant women. FASEB I 1995:9:A5658
in supporting insulin function (5). Insulin activity is known
(abstr).
to promote translocation of transferrin receptors to the
4. Liu X-N, Kang I, Zhao L, Viteri FE. Intermittent iron supplementation plasma membrane (6)-an action analogous to its translo-
is efficient and safe in controlling iron deficiency and anemia in cating effect on the GLUT 4 transporter. Because, save in
preschool children. Food Nutr Bull 1995;l6:139-46. the presence of iron deficiency, the availability of transfernin
5. Gross R, Schultink W, Juliawati. Treatment of anemia with weekly receptors is rate-limiting for intracellular iron uptake (7),
iron supplementation. Lancet I 994:344:821. reduced transferrin saturation during chromium supplemen-
6. O’Neil-Cutting MA, Crosby WH. Blocking of iron absorption by a tation might be expected if the chromium does indeed en-
preliminary oral dose of iron. Arch Intern Med 1987:147:489-91. hance net insulin activity.
7. Sloan NL, Jordan EA, Winikoff B. Does iron supplementation make a The simultaneous increase in TIBC and reduction in trans-
difference? Arlington, VA: Mother Care Project, 1992 (Working paper
ferrmn saturation reported during exercise with chromium
IS).
picolinate implies a 24% increase in free transferrin binding
8. World Health Organization, Maternal Health and Safe Motherhood
sites (apotransfernin). Apotransfernin is one of the most
Programme. Division of Family Health. Iron supplementation during
important antioxidants in serum owing to its ability to
pregnancy: why aren’t women complying? A review of available
sequester free extracellular iron (8), which, along with free
information. Geneva: World Health Organization Division of Family
Health, 1990.
copper, may be an obligate catalyst of hydroxyl radical
9. UNDP. Human development report 1991. Data from WHO. Oxford, generation in the extracellular space (and thus key to low-
United Kingdom: UNDP/Oxford University Press. 1991. density lipoprotein oxidation) (9). If it can be confirmed that
10. Viteri FE. Iron deficiency in children: new possibilities for its control. exercise, in conjunction with supplemental chromium, does
Int Child Health 1995:6:49-62. increase apotransferrin concentrations, this may have impor-
 LETTERS TO THE EDITOR 891

tant implications for prevention of atherosclerosis and other Reply to MF McCarty

free radical-related pathologies.
However, the findings of this study are questionable in
Dear Sir:
light of the comparatively trivial effect of supplemental
chromium picolinate on the serum and urine chromium McCarty (I) questions the conclusion of the recent finding (2)
concentrations. Previous studies with supplemental chro- that chromium picolinate supplementation of young men partici-
mium picolinate (200-400 ag Cr/d) report 6-10-fold in- pating in resistance training effects body iron transport and distri-
creases in urinary chromium (10, 1 1). In contrast, Lukaski et bution. He reiterates that a “trend” was reported for decreased
al’s study notes an increase of only =30% in these mea- transfernin saturation when chromium picotinate was consumed
sures. The observed increase in serum chromium was even and indicates that the cited reference (3) supporting the reported
smaller. Possible explanations for this discrepancy may be findings used extraphysiologic doses of administered chromium.
capsules with limited bioavailability, poor compliance of the Although we concur that the doses of chromium used by Ani
research subjects, concurrent ingestion of other supplements and Moshtaghie (3) exceeded the expected range of chromium
absorbed from the diet, this dose ( I mg Cr/kg body wt intra-

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containing chromium, or flawed chromium assay
techniques. penitoneatly for 45 d) resulted in anemia in the injected ani-
In any case, the possibility that chromium might influence mats. The effect of chromium picolinate supplementation (200
iron metabolism by modulating insulin function is intriguing jag/d for 8 wk) in our study was a disruption of iron metabolism
and merits follow-up. manifested by decreased transfernin saturation. Some points
merit additional discussion.
Mark F McCam’
Examination of the data indicates that chromium supplemen-
tation, regardless of chemical form, was associated with in-
creased serum chromium concentrations ( 1-3 nmol/L). How-
Research and Development
ever, the decrease in transferrin saturation was exaggerated
Nutrition 21
(24% compared with 12%) with chromium picolinate but not
1010 Turquoise Street, Suite 335
chromium chloride supplementation. This observation suggests
San Diego, CA 92109-1268 that picolinic acid may exert an additional effect on body iron
metabolism. Thus, the increase in serum chromium concentra-
tion seen with chromium picolinate supplementation should

REFERENCES also increase circulating picolinate concentration. In this man-

ner, picolinate may bind iron and reduce the amount of iron
1. Lukaski HC. Bolonchuk WW. Siders WA, Milne DB. Chromium available to bind to transferrmn and to alter body iron pools.
supplementation and resistance training: effects on body composition, Additional evidence of altered iron metabolism is provided by
strength, and trace element status of men. Am I Clin Nutr the observation of decreased urinary iron excretion when chro-
1996:63:954-65. mium picolinate supplements are consumed.
2. Ani M, Moshtaghie AA. The effect ofchromium on parameters related
McCarty (1) speculates that the reduction in transferrin sat-
to iron metabolism. Biol Trace Elem Res l992;32:57-64.
uration associated with chromium picolinate supplementation
3. Lee NA, Reasner CA. Beneficial effect of chromium supplementation
may exert beneficial effects on insulin and transferrin metab-
on serum triglyceride levels in NIDDM. Diabetes Care
olism. We are unable to address the role of chromium picoli-
1994:17:1449-52.
nate on insulin status and apotransferrin concentrations because
4. Wintrobe MM. Thorn GW. Adams RD. et al. eds. Harrison’s princi-
pIes of internal medicine. 7th ed. New York: McGraw-Hill Book
we did not measure fasting insulin, circulating apotransferrmn,
Company, 1974.
or transferrin receptor concentrations. These questions can only
5. Mertz W. Chromium in human nutrition: a review. I Nutr be examined by well-designed experiments.
1993:123:626-33. Some concerns expressed by McCarty regarding the quality
6. Davis RI. Corvera S. Czech MP. Insulin stimulates cellular iron uptake of analytical determinations, subject compliance. and product
and causes the redistribution of intracellular transfernin receptors to the quality are without basis. Our analytical values for serum and
plasma membrane. I Biol Chem 1986:261:8708-I 1. urinary chromium are similar to those published previously for
7. Baker E. Morgan EH. Iron transport. In: Brock IA, Halliday 1W, healthy subjects and supplemented diabetics. Self-reports and
Pippard MI. Powel LW. eds. Iron metabolism in health and disease. interviews with registered dietitians indicated clearly that the
London: WB Saunders, 1994:63-92. men did not consume self-prescribed nutritional supplements;
8. Stocks I. Gutteridge JMC. Sharp RJ. Dormandy TL. The inhibition of
consumption of chromium supplements and placebos was mon-
lipid autoxidation by human serum and its relation to serum proteins
itored periodically to ensure compliance. The question of bio-
and a-tocopherol. Clin Sci Mol Med l974;47:223-33.
availability of chromium in the chromium picolinate capsules
9. Smith C, Mitchinson MI. Aruoma 01, Halliwell B. Stimulation of lipid
was not considered an issue because we used supplements from
peroxidation and hydroxyl-radical generation by the contents of human
the same source as reported in other studies (6, 7) that implied
atherosclerotic lesions. Biochem I I 992:286:90 1-5.
positive effects of chromium picolinate. One explanation of the
10. Anderson RA, Polansky MM, Bryden NA, Zawadzki 1K. Selective
uptake of chromium in type II diabetes mellitus. FASEB I 1996;lO:
apparent disparity in blood and urinary chromium data between
A820 (abstr). the young men and the diabetic patients (6, 7) is chromium
I I . Gargas ML, Norton RL, Paustenbach DI, Finley BL. Urinary excretion status before the supplementation trials. Apparently, the young
of chromium by humans following ingestion of chromium picolinate. men had better chromium nutritional status than the diabetics,
Drug Metab Dispos 1994:22:522-9. who apparently had marginal chromium nutniture.