Chromium in livestock nutrition

Chromium was first reported as an essential mineral in rats (Schwarz and Mertz., 1959) and was demonstrated as an essential mineral for humans in 1977 (Jeejebhoy et al., 1977).The major focus of chromium research was given on the association between chromium and diabetes mellitus. It was as late as in the 1990s that chromium also started to be studied intensively as an essential mineral in livestock animals.

Chromium stands 21st in abundance among the minerals on the earth crust. Although chromium may theoretically occur in all oxidation states from –2 to +6, it is most often found in the trivalent and hexavalent forms. Trivalent chromium (Cr3+) is the most stable oxidation state in which chromium is found in living organisms and is considered to be a highly safe form of Chromium (Lindeman, 1996). Hexavalent chromium is mostly of industrial origin and is the one associated with chromium toxicity.

The primary role of chromium in metabolism is in enhancing the glucose uptake by the cells (Davis and Vincent, 1997). Chromium also activates certain enzymes and stabilizes proteins and nucleic acids (Anderson, 1994). Chromium supplementation reduces the negative effects of environmental stress (Sahin et al., 2001; Mowat, 1994; Lien et al., 1999). Supplemental dietary chromium is recommended by NRC (1997) for animals undergoing environmental stress. For laboratory animals, 300 µg Chromium /kg diet is recommended (NRC, 1995).

Even though chromium is not currently considered as an essential trace mineral for poultry, research data provide evidence that suggests a nutritional and physiological role for chromium as a micronutrient (Sands and Smith., 1999). The beneficial effects of chromium can be observed more efficiently under environmental, dietary, and hormonal stresses. Intake of 50-200 ppb of trivalent chromium is recommended for adult humans (NRC, 1989). Currently there are no NRC recommendations for chromium in poultry diets (NRC, 1994). In ruminants, supplementation of Chromium is recommended during heat stress periods, early lactation, infection etc. A level of 4-5 mg/head/day of supplemental actual chromium during the last 3 weeks prepartum and 5-6 mg/head/day during the first few weeks postpartum may suffice.


1. Sources of trivalent chromium

The major organic sources of chromium include chromium propionate, chromium picolinate, chromium nicotinate and high chromium yeast. Organic source of chromium is over ten times more bio available than inorganic sources (Lyons, 1994). Comparative studies of chromium (III) picolinate and niacin-bound chromium (III), two popular dietary supplements, reveal that chromium (III) picolinate produces significantly more oxidative stress and DNA damage. Studies have implicated the toxicity of chromium picolinate in renal impairment, skin blisters and pustules, anemia, hemolysis, tissue edema, liver dysfunction; neuronal cell injury, enhanced production of hydroxyl radicals, chromosomal aberration and DNA damage (Bagchi et al., 2002). Chromium picolinate has been shown to be mutagenic and picolinic acid moiety was inferred to be responsible as studies show that picolinic acid in the absence of chromium is clastogenic (Stearns et al., 1995). Chromium propionate (Kemin Industries Inc, USA) has been approved as an acceptable additive for swine feed by US Food and Drug Administration. This is based on the genotoxicity studies which proved it to be nontoxic (Anon., 2007). There are significant differences in the levels of response depending upon the source of chromium supplementation. Studies in pigs have shown that chromium from chromium propionate when compared to that from chromium picolinate gives significant metabolic responses, thus demonstrating excellent and reliable bioavailability (Matthews et al., 1997).


2. Chromium- Role in metabolism

2.1. Glucose metabolism

Low-molecular-weight chromium -binding substance, chromodulin is assumed to take part in the glucose metabolism. Chromodulin is a naturally-occurring oligopeptide composed of glycine, cysteine, aspartate and glutamate (Yamamoto et al. 1987). Chromodulin binds chromic ions in response to an insulin-mediated chromic ion flux, and the metal-saturated oligopeptide can bind to an insulin-stimulated insulin receptor, activating the receptor’s tyrosine kinase activity. Thus, chromodulin appears to play a role in an auto amplification mechanism in insulin signaling (Vincent, 2000a).

The molecule binds four equivalents of Cr3+, despite its small size. It carries chromium into the urine after the intake of large dosages of chromium, both trivalent and hexavalent forms (Wada et al. 1983) and can, therefore, assist in chromium detoxification. Chromodulin has been shown to activate the tyrosine kinase activity of insulin-activated insulin receptor (Davis et al. 1997; Davis & Vincent, 1997) and to activate a membrane phosphotyrosine phosphatase in adipocyte membranes (Davis et al. 1996). For example, the addition of bovine liver chromodulin to rat adipocytic membranes in the presence of 100 nM-insulin results in an up to eight-fold stimulation of insulin-dependent protein tyrosine kinase activity, while no activation of kinase activity is observed in the absence of insulin (Davis & Vincent, 1997). Chromium deficiency is found to cause reduction in insulin sensitivity in the peripheral tissues as well as a decrease in growth rate (Lindeman, 1996).

Vincent (2000a) proposed the mechanism by which chromodulin takes part in the insulin signaling. According to this, apochromodulin is stored in insulin-sensitive cells. In response to increases in blood insulin concentrations insulin binds to its receptor, bringing about a conformation change that results in the autophosphorylation of tyrosine residues on the internal side of the receptor. This process transforms the receptor into an active tyrosine kinase and transmits the signal from insulin into the cell. In response to insulin chromium is moved from the blood to insulin-sensitive cells. Here, the chromium flux results in the loading of apochromodulin with chromium. The holochromodulin then binds to the receptor, presumably assisting in the maintenance of the receptor in its active conformation, amplifying the receptor’s kinase activity. When the signaling is to be turned off, a in blood insulin levels facilitates relaxation of the conformation of the receptor, and the holochromodulin is excreted from the cell into the blood. Ultimately, chromodulin is efficiently excreted in the urine. The Fe-transport protein transferrin has been shown to be responsible for maintaining Cr3+ levels in the blood plasma and for transporting chromium to tissues in an insulin-responsive manner (Vincent, 2000a; Clodfelder et al. 2001). The basis of the name chromodulin is the similarity of this proposed mechanism of action to that of the Ca-binding protein calmodulin (Vincent, 2000b). Both molecules bind four equivalents of metal ions in response to a metal ion flux and both holoproteins selectively bind to kinases and phosphatases, thus stimulating their activity. The chromodulin mediated increase in the IR’s tyrosine kinase activity is expected to enhance the regulated movement of glucose transporter GLUT4 and, subsequently, enhance glucose disposal.

Another aspect of chromium action that may explain, at least in part, its enhancement of insulin sensitivity is its effect on increasing membrane fluidity and the rate of insulin internalization (Evans and Bowman, 1992). Moderate increase in plasma membrane fluidity have been documented to increase glucose transport. Furthermore, it has been shown that basal glucose transport is not fully active in fat cells and that it can be increased further by augmenting membrane fluidity (Pilch et al., 1980). The antidiabetic drug metformin was found to enhance insulin action by increasing membrane fluidity (Muller et al., 1997; Wiernsperger, 1999). As has been observed after chromium treatment (Cefalu et al., 2002), metformin treatment has been reported to increase GLUT4 translocation (Hundal et al., 1992; Pryor et al., 2000). It has recently been hypothesized that chromium enhances GLUT4 translocation through a cholesterol dependent mechanism. Plasma membrane cholesterol content was diminished in cells exposed to chromium and exogenous cholesterol replenishment was found to render the enhancement of insulin action by chromium ineffective (Chen et al., 2006). Although the expected biological outcome is observed the signaling molecules responsible for the same has not been evaluated.


2.2. Lipid metabolism

Chromium is found to increase the synthesis of fat in the adipose tissue and decrease the net release. This is assumed to be through linkage of chromodulin with the insulin receptor and the increased glucose flux into the adipocyte. Chromium is also found to influence the metabolism of cholesterol and triglycerides although the mechanism is not established. It is assumed to occur by means similar to that by the antidiabetic drug metformin. Metformin has been reported to activate 5_-AMP-activated kinase (AMPK) and the metformin- stimulated AMPK activity has been shown to suppress expression of a sterol regulatory element binding protein, SREBP-1 (Zhou et al., 2001), which belongs to a family of key lipogenic transcription factors directly involved in the expression of more than 30 genes dedicated to the synthesis and uptake of cholesterol, fatty acids, triglycerides, and phospholipids, as well as the reduced nicotinamide adenine dinucleotide phosphate cofactor required to synthesize these molecules (Brown and Goldstein, 1997).


2.3. Protein Metabolism

Evans and Bowman (1992) have demonstrated increased amino acid and glucose uptake by skeletal muscles of rats that had been incubated with chromium. This alteration in uptake of nutrients was associated with the alteration of insulin parameters and thus dependent on chromium. Roginski and Mertz (1969) observed that chromium supplementation increases amino acid uptake by tissues and also intensifies the incorporation of amino acids into heart proteins in rats.


2.4. Nucleic acid metabolism

Chromium in the trivalent state is assumed to be involved in the structural integrity and expression of genetic information in animals. Chromium protects RNA against heat denaturation. Chromium participates in gene expression by binding to chromatin, causing an increase in initiation loci and consequently, an increase in RNA synthesis. Okada et al. (1982) showed an interaction of chromium with DNA templates that resulted in a significant stimulation of RNA synthesis in vitro. Chromium is thought to have a role in nucleic acid metabolism because an increase in stimulation of amino acid incorporation into liver protein was observed during in vitro studies (Weser and Koolman, 1969).


3. Chromium and stress

The stress relieving effect of chromium has been well studied. Stress factors stimulate the hypothalamus leading to the production of corticotropin releasing factor, which stimulates the pituitary to produce adrenocorticotropic hormone, which in turn stimulates the adrenal cortex to increase the production and release of corticosterone (Siegel, 1995).

Corticoids depress the immune system function, and reduce serum protein concentrations. They also increase blood glucose concentration and reduce the glucose utilization by peripheral tissues thus functioning as insulin antagonists. Chromium is found to influence the secretion of corticosteroids. A number of reports confirm decreased sensitivity to stress in chromium supplemented animals through a reduced concentration of cortisol in blood (Chang and Mowat, 1992; Moonsie-Shageer and Mowat, 1993; Pechova et al., 2002). Chromium excretion in urine is found to be enhanced by all stress-inducing factors (Mowat, 1994).


4. Chromium on improving the immune function

Although chromium is believed to have different kinds of inborn, humoral and cellular immunomodulatory effects, the fundamental mechanism of intercellular and intracellular action remains unknown. The immune function may be affected in association with insulin and/or cortisol activity since corticosteroids have a depressing effect on immune system. It is also assumed to be mediated by production and regulation of certain cytokines (Borgs and Mallard, 1998).


5. Chromium: Benefits of supplementation in poultry

5.1. Chromium on egg production, egg quality and egg cholesterol levels in laying hens

Dietary chromium supplementation has been shown to positively affect the egg production and performance in laying hens (Sahin et al., 2001; Sahin et al., 2002). The beneficial effects of chromium could be observed more efficiently under environmental, dietary, and hormonal stresses. Chromium supplementation has been observed to alleviate the detrimental effects of cold stress in laying hens reared under a low ambient temperature (Sahin and Sahin, 2002). Similarly the egg production and egg quality of laying Japanese quails, reared under heat stress conditions, were found to be improved by chromium supplementation (Sahin et al., 2002). Southern and Page (1994) recommended 100-200 ppb of chromium as the optimum requirement for enhanced egg production in layers. The authors recorded an increase of 5.3% in egg production with 100 ppb dosage and a reduction in egg production was noticed at doses of 400 ppb and above. Few of the studies suggested higher optimum dosages (Sahin and Sahin, 2002; Sahin et al., 2001). Odgaard and Greaves (2001) suggested 100-200 ppb as the optimum dosage of chromium propionate as an animal feed supplement. The variation in the optimum dosage for egg production in different studies must be due to the difference in chromium source and experimental conditions.

Supplemental chromium was found to improve the feed efficiency in laying Japanese quails under heat stress (Sahin et al., 2002). Uyanik et al. (2002) observed improvement in the efficiency of feed utilization of laying hens with the supplementation of chromium as chromium chloride.

Improvement in egg quality traits such as specific gravity, eggshell thickness, eggshell weight and Haugh unit were observed as a result of chromium supplementation. Sahin et al. (2001) stated that supplemental chromium improved egg weight, egg specific gravity, eggshell thickness, eggshell weight and Haugh unit in laying hens reared under a low ambient temperature. Improvement in egg quality traits was observed with chromium supplementation in laying Japanese quails exposed to heat stress (Sahin et al., 2002). However, Lien et al. (1996) reported that the shell thickness was not affected by chromium picolinate supplementation under thermally neutral conditions. Southern and Page (1994) also observed that the egg quality traits such as Haugh units and the specific gravity were not significantly affected by chromium supplementation, which indicates that a marked beneficial effect on egg quality is observed only under conditions of stress.

Chromium supplementation markedly decreased blood cholesterol concentrations in Japanese quail under thermo neutral zone (Sahin et al., 2001a). A lowering trend in egg cholesterol levels were observed in hens when supplemented 100 or 200 ppb organic chromium (Southern and Page, 1994).

Significant reduction in serum corticosterone levels were reported in laying Japanese quail supplemented with chromium (Sahin et al., 2002). Sahin et al. (2001) found that chromium supplementation increased serum insulin concentration while markedly decreasing corticosterone concentration in laying hens at low ambient temperature.


5.2. Chromium effect on broiler performance

It has been shown that heat stress has detrimental effects on the performance of broiler birds reducing the growth rate and feed intake, also affecting the feed efficiency, carcass quality and health of the birds. (Carmen et al., 1991; Yahav et al., 1996; Temim et al., 2000; Har et al., 2000). Chronic heat stress increases the time to reach market weight and also increases mortality rate. Chromium supplementation has been observed to alleviate the adverse effects of heat stress on broilers.

Chromium supplementation has been found to improve the body weight gain and feed efficiency in broilers under heat stress conditions (Sands and Smith, 1999). Toghyani et al. (2006) reported an increase in body weight gain and feed intake of broilers under heat stress condition when supplemented with chromium. The authors also observed an increase in carcass yield and decrease in abdominal fat contents. Sahin et al. (2002a) reported an increase in feed intake, feed efficiency and body weight of broilers under heat stress with supplementation of chromium. Kim et al. (1996) observed that chromium supplementation increases the weight gain and feed intake in broilers without affecting the feed conversion. Increase in carcass yield and decrease in abdominal fat content in broilers was observed when supplemented with chromium picolinate (Sahin et al., 2003) or high chromium yeast (Debski et al., 2004). Sahin et al. (2003) observed that decrease in weight gain and feed efficiency in broiler birds, reared under heat stress conditions, was alleviated by dietary chromium supplementation. Chromium supplementation has been observed to improve FCR by 6.2% (Zhang et al., 2002).
Rosebrough and Steele (1981) observed that turkeys fed a diet supplemented with chromium had greater liver glycogen levels as a result of the increased activity of the enzyme glycogen synthetase, and also that chromium increased glucose transport by increasing insulin activity. Similarly, Cupo and Donaldson (1987) reported that chromium supplementation increased the rate of glucose utilization by 16%.

Kim et al. (1995) reported increased HDL cholesterol and decreased total in chromium supplemented broilers. However, Sands and Smith (2002) observed no significant differences in serum concentrations of cholesterol in broiler birds as a result of chromium supplementation. Anandhi et al. (2006) observed a significant reduction in breast and thigh muscle cholesterol levels and an increase in breast and thigh muscle protein levels in broilers supplemented with organic chromium. Chromium supplementation has been found to decrease the serum corticosterone and cholesterol levels in broiler chickens reared under heat stress (Sahin et al., 2002a).


6. Chromium: Benefits of supplementation in ruminants

6.1. Chromium: Effect on Milk production

High producing dairy cows goes under tremendous pressure and stress during early lactation stage. This causes negative energy balance, increased concentration of non esterified fatty acids (NEFA) and β- hydroxyl butyric acid (BHBA) in blood resulting in ketosis and other metabolic disorders leading to stress. Supplementation of Chromium is proven to be beneficial during these periods.

Several euglycemic clamp studies (Debrass et al.,1989; Prior and Christenson, 1978; Sano et al., 1991) ascertained that insulin resistance begins before parturition and continues during early lactation. Thus, during the periparturient period, insulin resistance may be an important factor in the initiation of catabolic activities (Holstenius, 1993). Improved glucose tolerance and milk yield and decreased blood cortisol, NEFA and BHBA were observed in primiparous cows with 0.5ppm of organic chromium supplementation (Subiyatno et al., 1996 ). Supplementing chromium has reduced blood cortisol concentrations and increased measures of immunological activity in transition dairy cows (Burton et al., 1994; Mallard et al., 1994; Chang et al., 1996).

Supplemental organic chromium increased milk yield by 11% during the first 14 weeks of lactation with first parity cows (Yang et al., 1996). It was observed that chromium supplementation tends to increase dry matter intake in first parity cows during the first 4-6 weeks postpartum. Dairy cattle provided chromium, as chromium propionate, ate more feed, and produced more milk than untreated cows (McNamara J. P. and F. Valdez 2003). Increased milk production might be an indirect effect of increased glucose production (Yang et al. 1996, McNamara J. P. and F. Valdez 2003).

Yang et al (1996) observed that chromium supplementation increased milk production observed in primiparous cows and not in multiparous cows. Besong et al. (1996) observed increased milk yield in the first 60 days of lactation in cows supplemented with chromium. Popovic et al. (2000) observed that first-lactation animals supplemented with 4 mg/day of an organic chromium supplement, had higher average daily milk yield and higher values for milk fat, protein, and lactose compared to the control group.


6.2. Chromium: Effect on calf growth

The normal husbandry practices in calf rearing, such as weaning, crowding, and feedlot acclimation could lead to physiological stress and in turn to a deficiency of chromium. Chromium excretion in urine during stress period increases the requirements. Supplemental chromium frequently decreases serum cortisol in chromium-deficient diets in stressed calves (Moonsie-Shageer and Mowat, 1993). Chromium supplementation to market and transit stressed feedlot calves resulted in increased rates of gain, feed efficiency, humoral immune responses, and reduced morbidity compared to unsupplemented control calves (Chang and Mowat, 1992). Chromium supplementation in market-transit stressed feeder calves was shown to improve growth performance during the first few weeks after arrival (Mowat et al., 1993). In contrast, when physiologically adapted calves were fed over longer feeding periods, growth performance was not affected by chromium supplementation (Chang et al., 1992). This indicates the specific requirement under conditions of physiological stress.

Dhiman et al (2007) observed that supplementation of chromium propionate decreased plasma cholesterol concentration in 6 months old male buffalo calves. Chromium supplementation was observed to enhance glucose clearance from the blood of growing Holstein calves (Bunting et al, 1994). Chromium supplementation in newly weaned calves has improved the antibody response to Infectious bovine rhinotracheitis vaccination (Burton et al, 1994). Supplementation of Chromium increased total weight gain and ADG and decreased blood cholesterol in young goats (Mondal et al., 2007).


Conclusion

Chromium is observed to play a key role in the carbohydrate, protein, and lipid metabolism and in improving the immune function. Organic source of chromium is found to be highly bioavailable and the beneficial effects of supplementation has been proven by various studies conducted in livestock. Chromium supplementation alleviates the negative effects of stress, thereby improves the performance and health of the livestock, leading to better farm profitability.


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