•
Chromium Requirements and Intake
The Estimated
Safe and Adequate Daily Dietary lntake (ESADDI) for chromium for children
7 years to adult is 50 to 200 µg per day(9).
The ESADDI is similar to an RDA (Recommended Dietary Allowance) and
is usually established prior to the RDA, e.g. the ESADDI for selenium
was converted to an RDA in 1989. Normal dietary intake of chromium
for adults is suboptimal based upon the recommended intakes and also
studies showing beneficial effects of supplemental chromium (see section
on Beneficial Effects of Supplemental Chromium). Normal dietary intake
of people in the U.S. is approximately 50 to 60% of the minimum suggested
daily intake of 50 µg. In the study of Anderson and Kozlovsky(10)
involving the 7-day intake of 32 subjects, determined using the duplicate
diet technique, none of the subjects averaged even the minimum suggested
intake and none of the individual diets provided even half of the
upper limit of the ESADDI. Similar intakes have been reported for
people in the U.S. and other Westernized countries(11).
Since only a small portion of the population is consuming the minimum
ESADDI for Cr of 50 µg, is the minimum ESADDI for Cr too high?
Based on numerous studies (there have been more than 30 studies reporting
beneficial effects of supplemental chromium on people with blood glucose
values ranging from marginally elevated to glucose intolerance and
diabetes (see review12),
there is no evidence that the minimum suggested intake for Cr is too
high, but rather that the majority of people are consuming suboptimal
amounts of dietary chromium.
Anderson
et al.(13) demonstrated
that consumption of normal diets in the lowest quartile of intake
(less than 20 µg per day) led to detrimental effects on the
glucose and insulin values in subjects with marginally impaired glucose
tolerance (90 min glucose between 100 to 200 mg/dl following an oral
glucose load of 1 g/kg). Consumption of these same diets by control
subjects (people with good glucose tolerance) did not lead to changes
in glucose and insulin variables. This is consistent with previous
studies demonstrating that the requirement for Cr is related to the
degree of glucose intolerance(14).
Not only
is the total dietary intake of chromium important, but also the total
diet consumed. For example, increased intakes of simple sugars lead
to increased losses of supplemental chromium(15).
This becomes a double-edged sword since high sugar foods are often
also low in chromium. Diets high in simple sugars lead to elevated
levels of circulating insulin and once insulin increases, chromium
is mobilised. Chromium does not appear to be reabsorbed by the kidney
and is lost in the urine.
•
Chromium Absorption via the Gastrointestinal Tract
Chromium
absorption is inversely related to dietary intake(10).
At daily dietary intakes of 10 µg, chromium absorption is approximately
2% and at intakes of 40 µg is 0.5%. This leads to an absorption
of approximately 0.2 µg per day which appears to be a minimal
basal level. At dietary intakes above 50 µg Cr per day, chromium
absorption is approximately 0.4%. The form of chromium also influences
the absorption, i.e. absorption of chromium from Cr chloride is usually
in the region of 0.4%(16)
and Cr from Cr picolinate approximately 1.2% at intakes of approximately
1000 µg per day(17).
Chromium incorporation into rat tissues was shown to vary widely depending
upon form(18). The
highest concentrations of chromium were found in the kidney followed
by liver, spleen, heart, lungs and gastrocnemius muscle. Control rats
fed a low Cr diet containing 30 ± 5 ng Cr g of diet and rats
given 5000 ng of Cr per g of diet in the form of Cr chloride, Cr histidine
and Cr nicotinate for three weeks, all displayed similar tissue levels
of Cr(18). Rats given
chromium in the form of Cr alum (Cr potassium sulfate), Cr nicotinic
acid histidine, Cr picolinate, Cr acetate, Cr glycine and a Cr nicotinic
acid glycine, cysteine glutamic acid complex all displayed significantly
greater levels of tissue Cr than the control animals.
In addition
to form, oxidation state and route of administration, ascorbic acid,
carbohydrates, phytate, oxalate, aspirin, antacids and indomethacin
also alter Cr absorption(19).
Ascorbic acid was shown to significantly increase Cr absorption in
humans(20) with similar
results in rats(21).
Using radioactively labelled Cr chloride, animals fed starch were
shown to have higher Cr absorption than those fed sucrose, fructose
or glucose(22). Phytate
has been reported to have either no effect on Cr absorption(23)
or an inhibitory effect(24).
Oxalate also inhibits Cr absorption(24).
Prostaglandin inhibitors such as aspirin and indomethacin enhance
Cr absorption(25)
and antacids, such as Maalox and Tums, inhibit Cr absorption(26).
•
Chromium Excretion
Absorbed
chromium is excreted primarily in the urine and only small amounts
are lost in the hair, perspiration or bile. Therefore, urinary Cr
excretion can be used as an indicator of Cr absorption. In addition
to factors discussed in the section on chromium absorption that alter
Cr excretion are various stresses including high sugar intake, exercise,
infection, pregnancy, lactation and physical trauma(27).
The more serious the stress, the greater the losses of chromium. Increases
in exercise intensity leading to greater degrees of stress assessed
by the stress hormone, cortisol, correlated with increases in urinary
Cr losses(28). While
urinary Cr losses are an indicator of stress and recent occupational
exposure, they cannot be used to assess Cr status.
Urinary
Cr losses for subjects consuming normal diets are approximately 0.1
to 0.3 µg per day with a urinary chromium: creatinine ratio
in the region of 0.1 to 0.2 ng Cr per mg of creatinine(16,28,29,30).
Tannery workers on a Friday afternoon were found to have chromium:
creatinine ratio of 0.83 ng/mg (1.80 mmol/mmol) compared with 0.18
ng/mg (0.39 mmol/mmol) for control workers.
Supplementation
of control subjects with 200 µg of Cr as Cr chloride for three
months increased the chromium: creatinine ratio to 1.43 mmol/mmol
of creatinine(30).
Levels from nutritional studies that lead to improvements in glucose,
insulin and blood lipids are in the same range as occupationally exposed
subjects such as tannery workers.
There
is a great deal of variation in urinary Cr levels for normals cited
by individuals working in the nutritional areas compared with those
of individuals involved in occupational exposure studies. However,
the control subjects should be similar in both groups. There are standard
reference samples available from the National Institute of Standards,
Gaithersburg, MD, and these should be used to ensure accurate results.
•
Beneficial Effects of Supplemental Chromium
The beneficial
effects of supplemental Cr on human subjects have been reviewed recently(12).
There are more than 30 studies reporting beneficial effects on subjects
with varying degrees of glucose intolerance ranging from marginally
elevated to those classified with overt diabetes. Subjects with varying
levels of blood lipids have also been shown to improve following Cr
supplementation with the greatest improvements in total cholesterol,
HDL-cholesterol and triglycerides in subjects with the highest initial
levels. It is beyond the space limitations of this article to review
all of these studies, but several recent studies serve to illustrate
the beneficial effects of Cr in subjects consuming normal diets with
normal life styles. In the past five years, Cr has been shown to improve
the signs and/or symptoms of diabetes in people with glucose intolerance(31)
and type 1(32), type
2(33), gestational(34)
and steroid-induced diabetes(35,36).
The amounts of supplemental Cr shown to have beneficial effects in
these studies ranged from 200 to 1000 µg per day. In the study
of Anderson et al.(33)
involving 180 subjects with type 2 diabetes mellitus (type 2 DM),
Cr effects were greater at 1000 µg per day than at 200 µg
per day. The most dramatic improvements were shown in hemoglobin A1C,
which is a reliable indicator of long-term glucose control. Hemoglobin
A1C in the placebo group was 8.5 ± 0.2%, 7.5 ± 0.2%
in the 200 µg group and 6.6 ± 0.1% in the group of subjects
receiving 1000 µg of Cr as Cr picolinate per day for 4
months. Laboratory values for control subjects normally range from
5.2 to 6.2%. Improvements in women with gestational diabetes were
also greater in a group receiving 8 µg per kg body weight per
day compared with those receiving 4 µg per kg body weight(34).
Steroid-induced diabetes that could not be controlled by oral hypoglycemic
medications and/or insulin was also improved to acceptable levels
in 47 of 50 people given 600 µg of Cr as Cr picolinate per day
for 2 weeks followed by a daily Cr maintenance dose of 200 µg(35,36).
Insulin sensitivity of obese subjects with a family history of diabetes
also improved following 1 000 µg daily of supplemental Cr as
Cr picolinate(31).
•
Safety of Supplemental Chromium
Trivalent
Cr, the form of Cr found in foods and nutrient supplements, is considered
one of the least toxic nutrients. The reference dose established by
the U.S. Environmental Protection Agency for Cr is 350 times the upper
limit of the Estimated Safe and Adequate Daily Dietary Intake (ESADDI).
The reference dose (RfD) is defined as “an estimate (with uncertainty
spanning perhaps an order of magnitude) of a daily exposure to the
human population, including sensitive subgroups, that is likely to
be without an appreciable risk of deleterious effects over a lifetime’’(37).
This
conservative estimate of safe intake has a much larger safety factor
for trivalent Cr than almost any other nutrient. The ratio of the
RfD to the ESADDI or RDA is 350 for Cr, compared to less than 2 for
zinc, roughly 2 for manganese, and 5 to 7 for selenium(37).
Anderson et al.(38)
demonstrated a lack of toxicity of Cr chloride and Cr picolinate in
rats at levels several thousand times the upper limit of the estimated
safe and adequate daily dietary intake for humans (based on body weight).
There was no evidence of toxicity in their study and there have not
been any reported toxic effects in any of the human studies involving
supplemental Cr.
•
Summary
In summary,
while there are numerous studies documenting the toxic effects of
hexavalent chromium, there are no documented negative effects of intakes
of trivalent Cr up to 1000 µg per day. There are more than 30
studies reporting beneficial effects of trivalent Cr in human subjects.
While problems associated with occupational exposure to Cr are limited
to a small segment of the population, the problems associated with
insufficient dietary Cr are likely to involve a large segment of the
population.
•
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