Recent Advances in the Clinical andBiochemical Manifestation of ChromiumDeficiency in Human andAnimal NutritionRichard A. Anderson*

Nutrient Requirements and Functions Laboratory, Beltsville Human Nutrition ResearchCenter, U.S. Department of Agriculture, ARS, Beltsville, Maryland

Several recent studies demonstrate that dietary Cr intake in humans and farm animals maybe suboptimal. Recent advances in Cr nutrition include the following: 1) Triglycerides ofsubjects with noninsulin-dependent diabetes (NIDDM) decreased following daily supple-mentation of 200mg of Cr. Glucose and cholesterol values were not affected. 2) HDLcholesterol of subjects taking beta-blockers for the control of hypertension improved fol-lowing supplementation with 600mg of Cr per day. 3) Chromium prevented sucrose-induced hypertension in spontaneously hypertensive rats but did not alter genetic hyper-tension. 4) The pig was shown to be a good experimental model for human Cr nutritionstudies. Supplemental Cr (300mg/Kg diet) improved glucose, insulin, HDL, and relatedparameters in pigs, similar to effects reported previously for humans. 5) Lean body massincreased and percent fat decreased in pigs receiving supplemental Cr, supporting earlierhuman studies suggesting that Cr effects body composition. 6) Litter size of pigs increasedfrom the lowest 10th percentile to the highest 10th percentile following Cr supplementation.7) Immune function improved in Cr-supplemented cattle. Improvements in immune func-tion were only present in the stressed animals. These recent advances document the nutri-tional role of Cr and demonstrate that the normal nutritional status of humans and farmanimals may be suboptimal. J. Trace Elem. Exp. Med. 11:241–250, 1998.© 1998 Wiley-Liss, Inc.†

Key words: glucose; insulin; cholesterol; triglycerides; diabetes; cardiovascular diseases; traceelements; body composition

INTRODUCTION

Recent advances in chromium nutrition continue to define new roles for Cr anddemonstrate that the dietary intake of Cr by humans and farm animals may besuboptimal. This review will deal primarily with studies published since my lastreview in this series [1] and the reader is urged to consult this and other reviews fora more general discussion of Cr nutrition research [2–4].

*Correspondence to: Dr. Richard A. Anderson, USDA, ARS, BHNRC, NRFL, Building 307, Room 224,BARC–East, Beltsville, MD 20705-2350.

Accepted 10 December 1997

The Journal of Trace Elements in Experimental Medicine 11:241–250 (1998)

© 1998 Wiley-Liss, Inc. †This article is a US Government work and, as such, is in the publicdomain in the United States of America.

PROD #341

Chromium, Hypertension, b-Blockers and Triglycerides

Evidence linking marginal Cr intake and risk factors of cardiovascular diseaseswere first reported more than 25 years ago [5]. Accident victims were shown to havehigher Cr concentrations in aortic tissue than patients who died of cardiovasculardiseases. Serum Cr is lower in subjects with coronary artery disease (CAD) than insubjects free of disease, and is highly correlated with CAD, while other more commonrisk factors such as serum cholesterol and triglycerides, blood pressure, and bodyweight are not correlated with the incidence of CAD [6]. Simonoff et al. [7] alsoreported that subjects with the highest incidence of CAD have the lowest concentra-tions of serum Cr. Serum Cr, like cineangiographic examinations, appears to be anindicator of CAD [7]. Roeback et al. [8] reported that HDL-cholesterol in 72 mentaking b-blockers for an average of 7 years improved following 2 months of Crsupplementation at 600mg/d. HDL of subjects on placebo continued to decline.b-Blockers decrease HDL-cholesterol and increase triglycerides [9]; therefore, peoplewho control their hypertension withb-blockers still have an elevated risk of CAD duelikely to decreased HDL and increased triglycerides. Chromium counteracts thesenegative effects ofb-blockers, even in people who have been onb-blockers for 7years or more. In a study involving 63 men and 13 women with CAD, Cr supple-mentation (250mg of Cr as Cr chloride) also led to significant improvements in HDLcholesterol [10]. HDL cholesterol increased from 34 ± 1.9 to 44.1 ± 2.7 mg/dLfollowing 7 to 11 months of Cr supplementation. Both diabetic and nondiabeticsubjects improved following Cr supplementation, and results for all subjects werecombined. Triglycerides also decreased 17% in a double-blind, placebo-controlledcrossover study involving 28 patients with NIDDM supplemented with 200mg of Cras Cr picolinate/d [11].

We recently reported that Cr prevents sucrose-induced hypertension in spontane-ously hypertensive rats [12], and studies to document a role of Cr in human hyper-tension are in progress. In these animal studies, beneficial effects of Cr were detect-able prior to changes in insulin, glucose, and related parameters.

Atherosclerosis diseases are responsible for more than 75% of the hospital admis-sions, and 45% of the inhabitants in the Western world will die of the consequencesof atherosclertic diseases [13]. Atherosclerosis is preventable. It is estimated that onein 500 people dies of the genetic form of heart disease—namely, heterozygous fa-milial hypercholesteromia. Therefore, 499 of 500 people have control over whetherthe buildup of plaque in arteries will be allowed to continue to cause ischemia orinfarction. Similarly, the major portion of people with NIDDM determine the inci-dence and progress of this disease. Therefore, improved Cr nutrition (which is asso-ciated with improved glucose, insulin, and lipid metabolism, as well as effects onhypertension) should be of significant benefit to these patients, and proper Cr nutritionshould serve to prevent or alleviate the incidence of NIDDM and CAD. Large scalestudies to document the role of Cr in NIDDM and cardiovascular diseases are neededto solidify the role of Cr as one of many factors in the prevention of diabetes andcardiovascular diseases. Small-scale studies have documented a role of proper Crnutrition in the alleviation of risk factors associated with NIDDM and cardiovasculardiseases (see previous reviews [1–4,14]), but large scale epidemiological studies areneeded.

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Pigs as an Experimental Model for Chromium Nutrition Studies

The rat is the usual model for nutrient studies, but in the rat signs of Cr deficiencyare difficult to demonstrate. Early studies of Mertz and Schwarz [15,16] reportedovert signs of Cr deficiency, but recent studies have reported less obvious signs of Crdeficiency. It appears that some factor or factors in the diet (or possibly the rats) weredifferent—leading to overt signs of deficiency. In the more recent studies, eventhough the Cr content of the diet was several-fold lower and the animals were raisedin plastic cages with purified air [17–20], the signs of Cr deficiency were not as largeas those reported by Mertz and Schwarz [15,16].

The pig appears to be a better experimental model for Cr deficiency studies thanthe rat. Addition of supplemental Cr to pig diets leads to similar effects as thoseobserved in human studies involving Cr supplementation [21,22]. Supplemental Crleads to improved glucose and insulin in postprandial samples. Chromium also coun-teracts the negative effects of growth hormone on glucose and insulin variables.

Supplemental Cr also leads to increased lean body mass and litter size in pigs [23].The effects of Cr are greater in animals consuming a suboptimal diet, supporting theobservation that Cr counteracts some of the negative effects of dietary stresses.Chromium supplementation of pigs increases percentage of muscle by 7% and longis-simus muscle area by 18% [24]. This is accompanied by a 20% reduction in 10th-ribfat and a 19% decrease in serum cholesterol. Supplemental Cr as Cr picolinate (200mg/kg/feed) given to pigs during the growing–finishing phases increases total gainand accretion rate of muscle, and decreases total gain and accretion rate of fat [25].Boleman et al. [26] also reported that dietary supplementation of Cr picolinate in thefinishing phase of pig production increases muscle and decreases fat deposition.Results were not as conclusive in the study of Boleman et al. [26], in which Cr wasadded only in the finishing phase, as those of Mooney and Cromwell [25], where Crwas added both in the growing and finishing phases.

The effects of Cr are definitely related to form, and likely diet of mother andgrowing pigs also. We observed that a small change (roughly 10%) in total dietary Crdue to supplemental Cr as Cr picolinate led to significant changes in tissue Cr [22].Fluctuations in total Cr due to normal variations in the Cr content of the diet often donot lead to changes in tissue Cr. This supports the postulate that form of Cr and alsodietary variables alter Cr bioavailability.

Chromium and Lean Body Mass in Humans

Chromium has been reported to increase lean body mass in both male [27] andfemale subjects [28]. Beginning weight training college students and college footballplayers displayed an increase in lean body mass while consuming Cr as Cr picolinate[27]. Lean body mass of students supplemented with Cr, 200mg per day as Crpicolinate, increased 1.6 kg, while that of students on placebo increased only 0.04 kgduring the 40-day weight lifting study. In a separate study, lean body mass of footballplayers increased 2.6 kg in athletes taking Cr and only 1.8 kg in those on placeboduring a 42-day weight lifting study. Percent body fat of athletes on Cr also decreasedsignificantly, while decreases in percent body fat of football players on placebo wereinsignificant [27].

Follow-up studies to confirm these results have met with limited success [29].

Nutritional Role of Chromium 243

Hasten et al. [28] reported increased lean body mass in females on a weight trainingprogram consuming 200mg daily of supplemental Cr as Cr picolinate, but not inmales. It was postulated that 200mg of supplemental Cr may not be enough for themale subjects. Clansy et al. [30] did not observe any significant changes in lean bodymass, percent body fat, or muscle girth following supplementation of 200mg per dayof Cr as Cr picolinate, compared to the placebo group in football players on a weightregime for 9 weeks. Lefavi et al. [31] reported no significant effects of supplementalCr on lean body mass or percent body fat, but did report improvements in bloodcholesterol in weight training subjects consuming Cr as Cr nicotinate.

Hallmark et al. [32] completed a study involving 16 untrained males (ages 23 ± 4years) on a 12-week resistive exercise training program. The 16 subjects were pair-matched on initial strength levels and placed in either the Cr-supplemented (200mg/das Cr picolinate) or the placebo group. Increases in lean body mass in the Cr groupwere double that of the placebo group, but were not significant based on the Bon-feronni statistical treatment of the data. However, by paired t-test, there was a sig-nificant effect of Cr on lean body mass at theP < 0.01 level.

Associated with the exercise-induced changes in glucose, insulin, and strengthparameters, weight training exercise also leads to improved Cr absorption [33]. Chro-mium absorption (based on urinary Cr excretion) of a stable isotope of Cr increasedsignificantly following a single bout of exercise. Strength training (16 weeks) alsoincreased absorption [33].

The mechanisms for the improvements in glucose and insulin metabolism follow-ing exercise are unclear and likely involve several factors. One possible mechanismfor these improvements may involve Cr. Chromium regulates blood glucose by po-tentiating insulin activity, leading to increased insulin sensitivity [1]. Exercise trainingalters Cr distribution and excretion [34–38], leading to more efficient utilization ofglucose. The increased insulin sensitivity associated with supplemental Cr may alsobe improved by the compensatory mechanisms to conserve Cr, as observed in trainedvs. untrained athletes [36].

Chromium and Immune Function

Stress alters Cr metabolism, but Cr also counteracts the effects of stress [39]. Themechanism of how Cr counteracts stress may involve the effects of Cr on immuneresponse. During stress, glucose metabolism increases, cortisol increases, and Crmobilization and excretion also increase [37,39]. Blood cortisol is correlated withurinary Cr losses [37]. Cortisol acts antagonistically to insulin by preventing entry ofglucose into peripheral tissue such as muscle and fat to spare it for tissues of higherdemand (such as brain and liver [40]). Stress and glucocorticoids, like cortisol, havesuppressive effects on the immune system [41]. Therefore, the immune system maybe compromised when it is needed. In humans, as well as farm animals, immunoen-hancing compounds in times of stress may be needed. This would be particularly truein stressed and/or immunocompromised farm animals in which the response to eventhe best vaccines is poor [40]. Farm animals, like humans, display signs of Crdeficiency. Chang and Mowat [42] reported that Cr in the form of high Cr yeastincreased average daily gain by 30% and feed efficiency by 27% in steer calvesfollowing the stress of shipping. Chromium had no significant effects on the non-stressed animals. Supplemental Cr decreased serum cortisol and increased immuno-

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globulin M and total immunoglobins in the stressed animals. These effects were alsodiet-dependent [42], suggesting that form of dietary Cr or dietary Cr interactions alterthe beneficial effects of supplemental Cr on cellular immunity in stressed animals.Humoral immune responses of periparturient and early-lactating dairy cows were alsoimproved by supplemental Cr [43]. Moonsie-Shageer and Mowat [44] reported thataverage daily weight gain increased 27% for the Cr supplemented stressed feedlotcalves compared to the placebo animals. Chromium supplementation in the form ofhigh Cr yeast also caused increased immunoglobin levels and peak primary antibodyresponses. Serum cortisol was also reduced by supplemental Cr, and morbidity andrectal temperatures tended to be lower. These results were confirmed in a follow-upstudy utilizing Cr in the form of a high Cr yeast or a Cr amino acid chelate [45]. Inthat study, beneficial effects were reported on average daily gain, blood cholesterol,glucose, morbidity, immunocompetence, and disease resistance.

The mechanism of the beneficial effects of Cr on immune function likely involvesincreased insulin sensitivity, decreased cortisol (which is antagonistic to insulin), andincreased cyclic adenosine monophosphate (cAMP) phosphodiesterase. Striffler et al.[20] reported that Cr deficiency led to significant decreases in cAMP-dependentphosphodiesterase activity. Decreased cAMP-dependent phosphodiesterase activitywould lead to increased levels of cAMP, since this enzyme is involved in the deg-radation of cAMP. Therefore, improved Cr nutrition would lead to decreased cortisoland increased cAMP-dependent phosphodiesterase and improved immune function.

This series of studies not only demonstrates the beneficial effects of Cr on immunefunction, but also documents that farm animals, like humans, are often Cr-deficient.The signs of Cr deficiency are overt in the stressed animals. There have not been anyreported studies on the effects of Cr on the immune function of humans. This is animportant research area, and well controlled studies are urgently needed.

Form of Chromium Alters Tissue Incorporation and Biological Response

Conversion of Cr to a biologically active form (a form that potentiates insulinbioactivity) [46] is essential for the utilization of Cr. Tuman et al. [47] reported thatinsulin-potentiating complexes, but not simple inorganic Cr complexes such as Crchloride, lowered plasma glucose and triglycerides of genetically diabetic mice. Un-like control animals, diabetic mice appear to lose the ability to efficiently convert Crto a useable form. Humans with varying degrees of glucose intolerance also responddifferently to supplemental Cr. People with marginally impaired glucose toleranceusually respond to 200mg daily of Cr even as Cr chloride, which appears to be theleast bioavailable, while diabetes require higher amounts of Cr (see reviews [1,3]).Diabetics appear to convert Cr to a useable form less efficiently and have elevated Crabsorption [48].

The incorporation of different forms of Cr into the kidney of weanling rats supple-mented with various forms of Cr at 5 mg/kg of diet for 3 weeks is shown in Figure1 [49]. Raising animals in stainless steel (stainless steel is roughly 18% Cr) cages withstainless steel feed cups and drinking tubes did not lead to increased kidney Cr,compared to control animals consuming the same diet in plastic cages with no directcontact with metal. Consumption of diets high in Cr chloride and Cr histidine also didnot alter tissue Cr concentrations. Kidney Cr concentrations of rats consuming Cr asCr potassium sulfate, Cr nicotinic acid histidine, Cr picolinate, Cr acetate, and Cr

Nutritional Role of Chromium 245

glycine were similar and all significantly greater than those for Cr chloride, Crhistidine, and Cr nicotinate. The complex with the greatest incorporation into thekidney was the Cr nicotinic acid–glycine–cysteine–glutamic acid complex (CrNA-AA), with kidney Cr values for this complex significantly greater than those for otherCr complexes tested.

Chromium incorporation into the liver (Fig. 2) was roughly an order of magnitudelower than comparable values for the kidney (note changes in scale from Figure 1 toFigure 2). The highest liver Cr concentrations were observed for the picolinate,acetate, and the nicotinate amino acid complex. The spleen had similar Cr concen-trations following supplementation with the various forms of Cr [49].

Since the Cr nicotinic acid–glycine–cysteine–glutamic acid had the highest tissueCr incorporation and was postulated to be similar to the biologically active form of Crfound in brewer’s yeast [50], we tested the effects of varying levels of this complexon type II diabetics [51]. Type II diabetics (237 subjects) were divided into fourgroups and supplemented with 0, 200, 400, or 600mg of Cr as the CrNa-AA complexfor 6 months. Blood glucose, insulin, lipids, hemoglobin A1C, and related variableswere measured at 0, 3, and 6 months. Subjects continued to take their normal medi-

Fig. 1. Kidney chromium concentrations of rats consuming a low Cr or Cr supplemented diet at 5 mgof Cr per kg of diet of the designated Cr complexes for 3 weeks. Animals designated as ‘‘stainless’’ werefed the control low-Cr diet, but in stainless steel cages with stainless steel feed cups and drinking tubes.All other animals were raised in plastic cages without direct contact with metals. Complexes are all Crcomplexes: ALUM is a Cr–potassium–sulfate compound, NA-AA is a Cr–nicotinic acid–amino acidcomplex. Complexes, synthesis, and analytical determinations have been described [49].

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cations and were encouraged not to change their eating and exercise habits. Therewere definite improvements in all groups of subjects and effects of the varying levelsof Cr could not be differentiated from placebo effects.

The lack of response to the CrNA-AA complex in the diabetic subjects waspartially explained by a lack of incorporation of this complex by pigs [51,52]. Pigsappear to be a better model for Cr nutrition studies, and display Cr incorporationvalues for the various Cr complexes which more closely reflect those of humans thanthose observed for rats.

This was substantiated by a follow-up human study involving the supplementationof four forms of Cr to people with overt type II diabetes [53]. Fifty-seven subjectswith overt type II diabetes mellitus were randomized into four groups and supple-mented with 200mg of Cr per day for 3 months in a 6 month double-blind placebo-controlled crossover study. Forms of Cr tested were Cr chloride, Cr nicotinate, Crpicolinate, and CrNA-AA. Urinary Cr losses, which are a relative measure of Crabsorption, were 0.41 ± 0.06mg/d during the placebo period and were not signifi-cantly higher during Cr chloride, Cr nicotinate, and CrNA-AA supplementation [53].Urinary losses for the diabetics receiving Cr picolinate were 2.65 ± 0.27mg/d. UrinaryCr losses for control subjects are 0.22 ± 0.02 and increase to 0.99 ± 0.08mg/dfollowing 3 months of supplementation with 200mg of Cr as Cr chloride [54], and

Fig. 2. Liver chromium concentrations of rats consuming a low-Cr diet or Cr-supplemented diet at 5mg/kg diet of the designated Cr compounds (same conditions as Figure 1).

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larger increases in Cr losses are observed following daily supplementation with 200mg of Cr as Cr picolinate for control subjects [32]. There were trends in improvementsin the glucose and lipid parameters during the Cr supplementation periods, but therewere no consistent improvements due to any of the supplemental forms of Cr tested.These data confirm the basal urinary losses of people with diabetes mellitus aregreater than those of controls. Two hundredmg of supplemental Cr does not appearto be adequate to elicit consistent improvements in glucose, insulin, and lipid vari-ables of people with diabetes mellitus for the forms of Cr tested [53]. Supplementationof type II diabetics with 200 or 1,000mg of Cr as Cr picolinate resulted in signifi-cantly greater effects in the subjects consuming 1,000mg compared to subjectsconsuming 200mg [55]. Improvements were observed in glucose, insulin, cholesterol,and hemoglobin A1C.

SUMMARY

Insufficient dietary Cr intakes by humans and farm animals are prevalent. Im-proved dietary Cr intake leads to improved glucose, insulin, lipid, and immune re-sponses. Studies in swine demonstrate conclusively an effect of Cr on lean body masswhich is supported in human studies. There have been no detrimental effects ofsupplemental Cr in any of the Cr nutrition studies.

REFERENCES

1. Anderson RA: Recent advances in the clinical and biochemical effects of chromium deficiency. InPrasad AS (ed): ‘‘Essential and Toxic Elements in Human Health and Disease: An Update.’’ NewYork: Wiley-Liss, pp 221–234, 1993.

2. Anderson RA: Essentiality of chromium in humans. Sci Total Environ 86:75–81, 1989.3. Anderson RA: Chromium, glucose tolerance, diabetes and lipid metabolism. J Advancement Med

8:37–49, 1995.4. Mertz W: Chromium in human nutrition: A review. J Nutr 123:626–633, 1993.5. Schroeder HA, Nason AP, Tipton IH: Chromium deficiency as a factor in atherosclerosis. J Chronic

Dis 23:123–142, 1970.6. Newman HAI, Leighton RF, Lanese RR, Freedland NA: Serum chromium and angiographically

determined coronary artery disease. Clin Chem 24:541–544, 1978.7. Simonoff M, Llabador Y, Hamon C, Peers AM, Simonoff GN: Low plasma chromium in patients

with coronary artery disease and heart diseases. Biol Trace Elem Res 6:431–439, 1984.8. Roeback JR Jr, Mae K, Chambless LE, Fletcher RH: Effects of chromium supplementation on serum

high-density lipoprotein cholesterol levels in men taking beta-blockers. Ann Inter Med 115:917–924,1991.

9. Lardinois CK, Neuman SL: Effects of antihypertensive agents on serum lipids and lipoproteins. ArchIntern Med 148:1280–1288, 1988.

10. Abraham AS, Brooks BA, Eylath U: The effects of chromium supplementation on serum glucose andlipids in patients with and without non-insulin-dependent diabetes. Metabolism 41:768–771, 1992.

11. Lee NA, Reasner CA: Beneficial effect of chromium supplementation on serum triglyceride levels inNIDDM. Diabetes Care 17:1449–1452, 1994.

12. Preuss HG, Gondal JA, Bustos E, Bushehri N, Lieberman S, Bryden NA, Polansky MM, AndersonRA: Effects of chromium and guar on sugar-induced hypertension. Clin Nephrology 44:170–177,1995.

13. Roberts WC: Preventing and arresting coronary artery disease. Am Heart J 130:580–600, 1995.14. Anderson RA: Trace minerals and cardiovascular diseases. In Favier AE, Neve J, Faure P (eds):

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‘‘Trace Elements and Free Radicals in Oxidative Diseases.’’ Champaign: AOCS Press, pp 100–112,1994.

15. Schwarz K, Mertz W: A glucose tolerance factor and its differentiation from factor 3. Arch BiochemBiophys 72:515–518, 1957.

16. Mertz W, Schwarz K: Relationship of glucose tolerance factor to impaired glucose tolerance in ratdiets. Am J Physiol 196:614–618, 1959.

17. Campbell WW, Polansky MM, Bryden NA, Soares JH Jr, Anderson RA: Exercise training and dietarychromium effects on glycogen, glycogen synthase, phosphorylase and total protein in rats. J Nutr119:653–660, 1989.

18. Campbell WW, Polansky MM, Bryden NA, Soares JH Jr, Anderson RA: Dietary chromium andexercise training effects on glucose, cholesterol and related variables. J Trace Elem Exptl Med3:295–305, 1990.

19. Striffler JS, Polansky MM, Anderson RA: Dietary chromium enhances insulin secretion in perfusedrat pancreas. J Trace Elem Exptl Med 6:75–81, 1993.

20. Striffler JS, Law JS, Polansky MM, Bhathena SJ, Anderson RA: Chromium improves insulin re-sponse to glucose in rats. Metabolism 44:1314–1320, 1995.

21. Evock-Clover CM, Polansky MM, Anderson RA, Steele NC: Dietary chromium supplementationwith or without somatotropin treatment alters serum hormones and metabolites in growing pigswithout affecting growth performance. J Nutr 123:1504–1512, 1993.

22. Anderson RA, Bryden NA, Evock-Clover CM, Steele NC: Beneficial effects of chromium on glucoseand lipid variables of control and somatotropin pigs are associated with increased tissue chromiumand altered tissue copper, iron and zinc. J Anim Sci 75:657–661, 1997.

23. Lindemann MD, Wood CM, Harper AF, Kornegay ET, Anderson RA: Dietary chromium picolinateadditions improve gain: Feed and carcass characterization in growing-finishing pigs and increase littersize in reproducing sows. J Anim Sci 73:457–465, 1995.

24. Page TG, Southern LL, Ward TL, Thompson DL Jr: Effect of chromium picolinate on growth andserum and carcass traits of growing-finishing pigs. J Anim Sci 71:656–662, 1993.

25. Mooney KW, Cromwell GL: Effects of dietary chromium picolinate supplementation on growthcarcass characteristics and accretion rate of carcass tissues in growing finishing swine. J Anim Sci73:3351–3357, 1995.

26. Boleman SL, Boleman SJ, Bidner TD, Souther LL, Ward TL, Pontef JE, Pike MM: Effect ofchromium picolinate on growth, body composition, and tissue accretion in pigs. J Anim Sci 73:2033–2042, 1995.

27. Evans GW: The effect of chromium picolinate on insulin controlled parameters in humans. Int JBiosoc Med Res 11:163–180, 1989.

28. Hasten DL, Rome EP, Franks BD, Hegsted M: Effects of chromium picolinate on beginning weighttraining students. Int J Sports Nutr 2:343–350, 1992.

29. Anderson RA: Chromium and its role in lean body mass and weight reduction. Nutr Repts 11:41–46,1993.

30. Clansy S, Clarkson P, DeCheke M, Cunningham J, Nosaka K, Freedsen P, Valentine B: Chromiumsupplementation in football players. Med Sci Sports Exercise 24(suppl 5):S286, 1992.

31. Lefavi RG, Wilson GD, Keith RE, Anderson RA, Blessing DL, Hames CG, McMillan JL: Lipidlowering effect of dietary chromium (III)-nicotinic acid complex in male athletes. Nutr Res 13:239–249, 1993.

32. Hallmark MA, Reynolds TH, DeSouza CA, Dotson CO, Anderson RA, Rogers MA: Effects ofchromium on resistance training on muscle strength and body composition. Med Sci Sports Exercise28:139–144, 1996.

33. Rubin MA, Miller JP, Ryan AS, Treuth MS, Patterson KY, Pratley RE, Hurley BF, Veillon C,Anderson RA, Moser-Veillon PB: Acute and chronic resistive exercise increase urinary chromiumexcretion in men as measured with an enriched chromium stable isotope. J Nutr 128:73–78, 1998.

34. Anderson RA, Polansky MM, Bryden NA, Roginski EE, Patterson KY, Reamer DC: Effect ofexercise (running) on serum glucose, insulin, glucagon and chromium excretion. Diabetes 31:212–216, 1982.

35. Anderson RA, Polansky MM, Bryden NA: Strenuous running: Acute effects on chromium, copper,zinc, and selected clinical variables in urine and serum of male runners. Biol Trace Elem Res6:327–336, 1984.

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36. Anderson RA, Bryden NA, Polansky MM, Deuster PA: Exercise effects on chromium excretion oftrained and untrained men consuming a constant diet. J Appl Physiol 64:249–252, 1988.

37. Anderson RA, Bryden NA, Polansky MM, Thorp JW: Effect of carbohydrate loading and underwaterexercise on circulating cortisol, insulin and urinary losses of chromium and zinc. Eur J Appl Physiol63:146–150, 1991.

38. Vallerand AL, Cuerrier JP, Shapcott D, Vallerand RJ, Gardiner PF: Influence of exercise training ontissue chromium concentrations in the rat. Am J Clin Nutr 39:402–409, 1984.

39. Anderson RA: Stress effects on chromium nutrition of humans and farm animals. In ‘‘Biotechnologyin the Feed Industry,’’ Proceedings Alltech’s Tenth Annual Symposium. Nottingham: UniversityPress, pp 267–274, 1994.

40. Burton JL: Supplemental chromium: Its benefits to the bovine immune system. Anim Food Sci Tech53:117–133, 1995.

41. Kahansari DN, Murgo AJ, Faith RE: Effects of stress on the immune system. Immunol Today11:170–179, 1990.

42. Chang X, Mowat DN: Supplemental chromium for stressed and growing feeder calves. J Anim Sci70:559–565, 1992.

43. Burton JL, Mallard BA, Mowat DN: Effects of supplemental chromium on immune responses ofperiparturient and early lactation dairy cows. J Anim Sci 71:1532–1539, 1993.

44. Moonsie-Shageer S, Mowat DN: Effect of level of supplemental chromium on performance, serumconstituents and immune status of stressed feeder calves. J Anim Sci 71:232–238, 1993.

45. Mowat DN, Chang X, Yang WZ: Chelated chromium for stressed feeder calves. Can J Anim Sci73:49–56, 1993.

46. Anderson RA, Brantner JH, Polansky MM: An improved assay for biologically active chromium. JAgric Fd Chem 26:1219–1221, 1978.

47. Tuman RW, Bilbo JT, Doisy RJ: Comparison and effects of natural and synthetic glucose tolerancefactor in normal and genetically diabetic mice. Diabetes 27:49–56, 1978.

48. Doisy RJ, Streeten DHP, Freiberg JM, Schneider AJ: Chromium metabolism in man and biochemicaleffects. In Prasad AS, Oberleas D (eds): ‘‘Trace Elements in Human Health and Disease, Vol II,Essential and Toxic Elements.’’ New York: Academic Press, pp 79–104, 1976.

49. Anderson RA, Bryden NA, Polansky MM, Gautschi K: Dietary chromium effects on tissue chromiumconcentrations and chromium absorption in rats. J Trace Elem Exptl Med 9:11–25, 1996.

50. Toepfer EW, Mertz W, Polansky MM, Roginski EE, Wolf WR: Preparation of chromium-containingmaterial of glucose tolerance factor activity from brewer’s yeast extracts and by synthesis. J Agric FdChem 25:162–166, 1977.

51. Anderson RA, Bryden NA, Polansky MM: Type II diabetes and chromium. In Neve J, Chappuis P,Lamand M (eds): ‘‘Therapeutic Uses of Trace Elements,’’ New York: Plenum Press, pp 161–165,1996.

52. Ward TL, Southern LL, Anderson RA: Effect of dietary chromium source on growth carcass char-acteristics and plasma metabolite and hormone concentrations in growing-finishing swine. J Anim Sci(Suppl 1):189, 1995.

53. Anderson RA, Polansky MM, Bryden NA, Zawadski J: Selective uptake of chromium in type IIdiabetes mellitus. FASEB J 10:A820, 1996.

54. Anderson RA, Polansky MM, Bryden NA, Patterson KY, Veillon C, Glinsmann WH: Effects ofchromium supplementation on urinary Cr excretion of human subjects and correlation of Cr excretionwith selected clinical parameters. J Nutr 113:276–281, 1983.

55. Anderson RA, Cheng N, Bryden NA, Polansky MM, Cheng N, Chi J, Feng J: Beneficial effects ofchromium for people with diabetes. Diabetes 46:1786–1791, 1997.

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