Stress Effects on Chromium Nutrition of Humans and Farm Animals

STRESS EFFECTS ON CHROMIUM NUTRITION OF
HUMANS AND FARM ANIMALS
RICHARD A. ANDERSON
Vitamin and Mineral Nutrition Laboratory, Beltsville Human Nutrition
Research Center, U.S. Department of Agriculture, ARS Beltsville,
Maryland, USA
Introduction
<strong>Stress</strong>, which can be defined as “abnormal pressure, strain, constraining
force or influence”, can occur in biological systems in various forms from
very mild dietary stresses to severe physical trauma or injury. While the
degree of stress can be approximated, a similar amount of stress can have
very different effects on different people or animals. For example, a mild
amount of exercise for one individual may be a rather extreme form of
stress for another.
Chronic stresses may also alter nutrient requirements. If dietary intake
is suboptimal, a small stress-induced alteration may have signiticant
effects on the signs and symptoms of deficiency. One metal that is
suboptimal in the diet and strongly influenced by stress in humans and
farm animals is chromium (Cr).
The essentiality of chromium was demonstrated in rats whose impaired
glucose tolerance was improved following Cr supplementation (Schwarz
and Mertz, 1959). Chromium has subsequently been shown to affect
glucose and(or) lipid metabolism in mice, squirrel monkeys, guinea
pigs, rabbits, chickens, turkeys, pigs, cattle and humans (Anderson,
1988). Documentation of the essential role of Cr in humans was first
reported in 1977 (Jeejeebhoy et al., 1977) for a woman on total
parenteral nutrition. The patient was on total parenteral nutrition for
five years. She became diabetic with severe glucose intolerance, weight
loss and impaired nerve conduction. Symptoms were refractory to the
daily addition of 45 units of insulin. Following the addition of 250 pg
of Cr as chromium chloride for two weeks, diabetic symptoms were
alleviated and exogenous insulin requirement dropped from 45 units/d
to zero. Intravenous glucose tolerance and respiratory quotient returned
to normal. This work has subsequently been confirmed in numerous
laboratories (Freund et al., 1979; Brown et al., 1986; Anderson, 1989).
Chromium is now routinely added to total parenteral nutrition solutions
(Anderson, 1994).
However, not all patients on total parenteral nutrition may require
supplemental Cr (Anderson, 1994). Chromium is often a contaminant
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<strong>Stress</strong> effects on chromium nutrition of humans aad farm animals
in parenteral nutrition fluids and extra chromium may not be required.
Chromium content of parenteral nutrition fluids should be monitored
routinely to prevent chromium accumulation especially in patients with
impaired kidney function.
Signs of Cr deficiency in humans are not limited to subjects on
total parenteral nutrition. Improvements in glucose and(or) lipid con-
centrations have been observed in children with protein calorie malnutri-
tion, adults and the elderly. Adults with low blood sugar, marginal to
impaired glucose tolerance and diabetics have all been shown to respond
to supplemental Cr (see review, Anderson, 1993).
The signs of Cr deficiency in humans and experimental and farm
animals shown to improve following supplemental Cr are listed in Table
1. Improvements following Cr supplementation may not be reversing
signs of deficiency but rather therapeutic effects. For example, some
early studies involving turkey poults (Steele and Rosebrough, 1979)
and pigs (Steele et al., 1982) involved Cr added to the diet at 20-200
pg/kg of diet. Recent studies show beneficial effects in the nutritional
range (100 to 1000 times lower) (Burton et al., 1992; Chang and
Mowat, 1992; Page et al., 1993; Evock-Clover et al., 1993). However,
true nutritional and therapeutic effects still need to be ascertained.
Glucose, lipids and body composition of animals consuming stock diets
containing presumably ample amounts of Cr (greater than 300 &kg)
often improve when supplemented with Cr. However, the form of Cr
used,may also be very important. Anderson et al. (1993) supplemented
rats with nine different forms of Cr and demonstrated that some forms
TabIe 1. Signs and symptoms of chromium deficiency.
Function Animals
Impaired glucose tolerance
Human, rat, mouse, squirre1 monkey,
guinea pig
Elevated circulating insulin Human, rat, pig
Glycosuria Human, rat
Fasting hyperglycemia Human, rat, mouse
Impaired growth Human, rat, mouse, turkey
Hypoglycemia Human
Elevated serum cholesterol and triglycerides Human, rat, mouse, cattle, pig
Increased incidence of aortic plaques Rabbit, rat, mouse
Increased aortic intimal plaque area Rabbit
Neuropathy Human
EncephaIopathy Human
Cornea1 Iesions Rat, squirrel monkey
Ocular eye pressure Human
Decreased fertility and sperm count Rat
Decreased longevity Rat, mouse
Decreased insulin binding Human
Decreased insulin receptor number HUmaIl
Decreased Iean body mass Human, pig, rat
Elevated per cent body fat Human, pig
HumoraI immune response Cattle
Morbidity Cattle
Source: Adapted from Anderson, 1988.
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R. A. Anderson
of Cr including inorganic chromium chloride, were incorporated poorly
into tissues. Chromium incorporation into rat tissues varied several-fold
among the Cr compounds tested (Anderson et al., 1993). Therefore, total
dietary Cr may be an inaccurate reflection of bioavailable Cr and a poor
reflection of Cr nutritional status.
<strong>Stress</strong> effects on human chromium nutrition
<strong>Stress</strong>es shown to alter Cr nutrition are glucose loading, high simple
sugar diets, lactation, infection, acute exercise, chronic exercise and
physical trauma (Table 2, Anderson, 1988). Urinary Cr losses can be
used as a measure of the Cr mobilized and lost since Cr is not reabsorbed
in the kidney but is excreted via the urine (Doisy et al., 1971).
Various forms of stress increase Cr losses and the degree of stress
is roughly related to the amount of Cr lost in the urine. For example,
mild aerobic exercise at 50% of V ozmax does not result in significant
increases in urinary Cr losses while exercise at 90% of Vozmax does
result in significant urinary Cr losses (Anderson et al., 1988). Running
a 10 km race at near maximal capacity resulted in nearing a doubling
of daily urinary Cr losses compared with a nonexercise day (Table 2,
Anderson et al., 1982). Urinary Cr concentration was almost five-fold
higher two hours following exercise compared with pre-exercise values.
Anaerobic exercise also leads to increased Cr losses (Vincient et al.,
1994). While acute strenuous aerobic and anaerobic exercise rest&s in
significantly enhanced Cr losses, aerobic training leads to decreased basal
Cr losses (Table 2; Anderson et al., 1988).
Chromium values listed in TabIe 2 were all determined in our Iabora-
tory at Beltsville by the same methods and can be compared directly.
BasaI urinary Cr concentrations varied greatly prior to 1980 but accepted
values are 0.12-0.22 kg/d for normal sedentary subjects. Decreased Cr
losses observed in response to aerobic training may be an indication of
decreased body Cr stores in response to repeated bouts of exercise.
Lower basal losses in trained subjects may also be an adaptive response.
If aerobic training led to increased Cr deficiency then people who are
well-trained would be expected to display increased signs of Cr deficiency
including impaired glucose tolerance and insulin resistance. However,
this is not the case and aerobically trained individuals have improved
glucose tolerance and insulin sensitivity (Rodnick et al., 1987). It is
Table 2. <strong>Stress</strong> effects on urinary Cr losses of humans.
<strong>Stress</strong> Urinary Cr, p&day Reference
Basal 0.16 + 0.0’2 Anderson et al., 1982
Acute exercise 0.30 f 0.07 Anderson et al., 1982
Chronic exercise (training) 0.09 t 0.01 Anderson et al., 1988
Lactation 0.37 + 0.02 Anderson et al., 1993
High sugar diet 0.28 ST 0.01 Kozlovsky et al., 1986
Physical trauma 10.8 f 2.1 Bore1 et al., 1984

<strong>Stress</strong> effects on chmmium nutrition of humans and farm animals
likely that training which leads to obvious adaptive increases in strength,
endurance, heart stroke volume etc. leads to increased conservation of
body Cr stores. Adaptive changes may involve a redistribution of Cr in
specific tissues which is supported by animal studies. Vallerand et al.
(1984) reported that exercise-trained rats displayed significantly higher
Cr concentrations in the heart and kidneys compared with respective
tissues of controIs. Humans who train regularly may also compensate for
increased Cr losses associated with acute exercise with increased caloric
intake, resulting in higher Cr intake. Improved dietary habits including
decreased consumption of simple sugars (which leads to enhanced Cr
Iosses) would aIso lead to improved dietary Cr status. However, peopIe
who exercise strenuously but sporadically to Iose weight would not have
increased dietary intake, would not have the adaptive mechanisms of
training, and would not have improved Cr nutrition, but would have
low intake coupled with high Cr losses due to acute exercise. This couId
obviously lead to decreased Cr stores.
A direct correIation of Cr losses with stress was shown by Anderson
et al. (1991; Figure 1) who reported a correlation of serum cortisol
and urinary Cr Iosses associated with strenuous head out immersion
exercise. Serum cortisol is reIated to the degree of exercise intensity
and is therefore a measure of exercise stress (Kuoppasalmi et al., 1980).
Increased exercise capacity associated with carbohydrate loading was
less stressful based on serum cortisol and also less stressful based on
decreased Cr Iosses (Anderson et al., 1991).
0 400 800 1200 1600
Post-exercise serum cortisol (nmol/l)
Figure 1. Correlation of urinary chromium losses and post-exercise serum cortisol.
Blood samples for serum cortisol were taken immediately following head out immersion
exercise at 25°C. Urine samples were collected during the four hours of exercise and
two hours following. (0) Control diet period; (I) following carbohydrate Ioading.(Source:
Anderson et al., 1991)
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R.A. Anderson
Severe forms of stress such as those associated with physical trauma
severe enough to be taken to a shock trauma unit resulted in severaLfold
increases in Cr losses (Table 2; Bore1 et al., 1984). Chromium losses
decreased as the patients improved and the degree of stress decreased.
<strong>Stress</strong> effects in farm animals
The effects of stress on Cr metabolism observed in humans are also
observed in farm animals. Chang and Mowat (1992) reported that Cr in
the form of high Cr yeast increased average daily gain by 30% and feed
efficiency by 27% in steer calves folIowing the stress of shipping. During
the growing period, Cr had no effect on weight gain or feed efficiency.
Chromium also decreased serum cortisol and increased immunogIobulin
M and total immunoglobins in caIves fed diets with soybean meal
but had no effect in calves fed urea-corn supplementation. Humoral
immune responses of periparturient and early lactating dairy cows were
also improved by supplementa Cr (Burton et al., 1993). These data
suggest that stressed animals fed normal diets may be showing signs
of Cr deficiency including decreased feed efficiency, increased stress
hormone, morbidity, and impaired immune function.
These signs of Cr deficiency are only observed in the stressed animals.
The stress associated with shipping appears to increase the Cr require-
ment of the steers. Long-acting oxytetracydine which is given to combat
stress has effects similar to Cr but when Cr and tetracycline were
administered GnuItaneousIy there were no additive effects. The authors
postulated that by reducing stress, long-acting injectable oxytetracycline
alleviated Cr Iosses and prevented signs of marginal Cr deficiency.
Klasing and Roura (1991) demonstrated that administration of antibiotic
to chicks decreased immunoIogic stress by reducing interleukin-1 Ievels
resuhing in unproved growth. Chromium supplementation to unstressed
growing-finishing steers had no effect on carcass composition and tissue
mineral concentrations or any performance characteristics. The benefica1
effects of Cr in stressed animals demonstrates that stress increases Cr
requirements.
Chromium-has also been shown to have beneficial effects on body
composition, glucose, Iipids and related parameters in swine. Steele et aI.
(1982) reported that high levels of insulin-potentiating or biologicahy
active Cr increased growth and feed efficiency in pigs. Page et al.
(1993) reported increased daiIy gain, Iongissimus muscle area, increased
percentage of muscling and decreased tenth rib fat in pigs following Cr
supplementation in the form of Cr picolinate but not with chromium
chIoride. Evock-CIover et al. (1993) reported improved HDL-choles-
terol, total cholesterol: HDL ratio, glucose, insulin and insuhnglucose
ratio in both control and growth hormone treated pigs following supple-
mentation with Cr in the form of Cr picolinate. Supplementa Cr
counteracted the negative effects of growth hormone on glucose and
insulin variables. Chromium effects were greater at 60 kg than at 4.5 kg.
Chromium also increased serum growth hormone in the growth hormone-
treated pigs.
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<strong>Stress</strong> effecfs on chromium nutrition of humans and farm animals
Page et al (1993) reported variable results on blood variables. For
exampIe, “serum cholesterol was reduced by Cr picolinate in Experi-
ments I and 2 but not affected by Cr picolinate in Experiment 3”. <strong>Effects</strong>
on body composition were aIso somewhat variable. In a follow-up study,
Evock-Clover et al. also did not observe as Iarge or consistent effects of
Cr as in the initial study (unpublished observations). Other investigators
have also found some inconsistencies in their studies involving Cr
nutrition in humans and animals. One important factor that has been
poorly controIled in all studies is stress. Variable responses to Cr may
be related to stress levels.
Summary
Dietary and physical stresses have profound effects on Cr nutrition
of humans and farm animaIs. <strong>Stress</strong> leads to increased Cr losses in
humans and may lead to higher Cr requirements. <strong>Stress</strong>-induced higher
Cr requirements have been documented in farm animals. While dietary
stress can be controlled quite closely, environmental stresses including
temperature, humidity and pathogens often vary considerably. External
pathogens as we11 as pathogens and toxins found in foods could lead
to altered Ievels of stress. Any or all of these stresses may alter Cr
metabolism and nutritional Cr requirements and function.
References
Anderson, R.A. 1988. Chromium. In: Trace MineraIs in Foods, K.Smith
(ed.) Marcel Dekker, Inc., New York.. p- 231.
Anderson, R.A. Chromium and parenteral nutrition. Nutrition (in
press).
Anderson, R.A. 1989. Essentiality of chromium in humans. Sci. Total
Environ. 86:75.
Anderson, R.A. 1993. Recent advances in the clinical and biochemical
effects of chromium deficiency. In: Essential and Toxic Trace Elements
in Human Health and Disease, A.S. Prasad, ed., Wiley Liss Inc., New
York. p. 221.
Anderson, R.A., N.A. Bryden, and M.M. Polansky. 1993. Form of
chromium effects tissue chromium concentration. FASEB J. 7:A204.
Anderson, R.A., N.A. Bryden, M.M. Polansky, and P.A. Deuster.
1988. Exercise effects on chromium excretion of trained and untrained
men consuming a constant diet. J. Appl. Physiol. 64:249.
Anderson, R.A., N.A. Bryden, M.M. Polansky, and J.W. Thorp. 1991.
Effect of carbohydrate loading and underwater exercise on circulating
cortisol, insulin and urinary losses of chromium and zinc. Eur. J. Appl.
Physiol. 63:146.
272

R.A. Anderson
Anderson, R.A., M.M. Polansky, N.A. Bryden, E.E. Roginski, K.Y.
Patterson, and D.C. Reamer. 1982. Effect of exercise (running) on
serum glucose, insulin, glucagon and chromium excretion. Diabetes
31:212.
Borel, J.S., T.C. Majerus, M.M. Polansky, P.B. Moser, and R.A.
Anderson. 1984. Chromium intake and urinary chromium excretion
of trauma patients. Biol. Trace Elem. Res. 6:317.
Brown, R-O., S. ForIoines-Lynn, R.E. Cross, and W.D. Heizer. 1986.
Chromium deficiency after long-term tota parenteral nutrition. Dig.
Dis. Sci. 31:661.
Burton, J.L., B.A. Mallard, and D.N. Mowat. 1993. <strong>Effects</strong> of supple-
menta1 chromium on immune responses of periparturient and early
lactation dairy cows. J. Anim. Sci. 71:1532.
Chang, X., and D.N. Mowat. 1992. Supplemental chromium for stressed
and growing feeder calves. J. Anim. Sci. 70:559.
Doisy, R.J., D.H.P. Streeten, M.L. Souma, M.E. Kalafer, S.L. Rekant,
and T.G. Dalakos.1971. Metabolism of chromium 51 in human sub-
jects. In: Newer Trace Elements in Nutrition, W. Mertz and W.E.
Cornatzer, eds., Marcel Dekker, New York. p. 155.
Evock-Clover, C.M., M.M. Polansky, R.A. Anderson, and N.C. Steele.
1993. Dietary chromium supplementation with or without somatotro-
pin treatment ahers serum hormones and metabolites in growing pigs
without affecting growth performance. J. Nutr. 123:1504.
Freund, H., S. Atamian, and J.E. Fischer. 1979. Chromium deficiency
during total parenteral nutrition. J. Am. Med. Assoc. 241:496.
Jeejeebhoy, K.N., R.C. Chu, E.B. Marliss, G.R. Greenberg, and A.
Bruce-Robertson. 1977. Chromium deficiency, glucose intoIerance,
and neuropathy reversed by chromium supplementation in a patient
receiving longterm total parenteral nutrition. Am. J. Clin. Nutr.
30:531.
Klasing, K.C. and E. Roura.1991. Interactions between nutrition and
immunity in chickens. Proc. Cornell Nutr. Conf. p. 94.
Kuoppasalmi, K., H. Naveri, M. Harkonen, and H. Aldercreutz. 1980.
Plasma cortiso1, androstinedione, testosterone and leutenizing hormone
in running exercise of different intensities. Stand. J. Clin. Lab. Invest.
40:403.
Page, T.G., L.L. Southern, T.L. Ward, and D.L. Thompson, Jr. 1993.
Effect of chromium picohnate on growth and serum and carcass traits
of growing finishing pigs. J. Anim. Sci. 71:656.
Rodnick, K.J., W.L. Haskell, A.L.M. Swislocki, J.E. Foley, and G.M.
Reaven. 1987. Improved insulin action in muscle, liver, and adipose
tissue in physically trained human subjects. Am. J. Physiol. 253:E489.
Schwarz,- K. and W. Mertz. 1959. Chromium (III) and the glucose
tolerance factor. Arch. Biochem. Biophys. 85:292.
Steele, N-C., M.P. Richards, and R.W. Rosebrough.1982. Effect of
dietary chromium and protein status of hepatic insulin binding char-
acteristics of swine. J. Anim. Sci. 55 (Suppl. 1):300.
Steele, N.C. and R.W. Rosebrough. 1979. Trivalent chromium and
nicotinic acid suppIementation for the turkey poult. Poult. Sci. 58:983.
273

<strong>Stress</strong> effects on chromium nutrition of humans and farm animals
Vallerand, A-L., J.P. Cuerrier, D. Shapcott, R.J. ValIerand, and P.F.
Gardiner. 1984. Influence of exercise training on tissue chromium
concentrations in the rat. Am. J. Clin. Nutr. 39:402.
Vincient, K.R., P.M. Clarkson, P.S. Freedson, and R.A. Anderson.
Weight training, carbohydrate feeding and chromium excretion. Am.
Coll. Sports Med. (in press).
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