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Casein represents a class of phosphoproteins (a, ß, K,y ) derived from bovine milk. Food scientists consider bovine casein as the fraction of milk that precipitates from raw milk at a pH of 4.6 and 200C. However, some whey protein may also precipitate under these same conditions, thereby contaminating the casein with lactalbumin and lactoferrin. Casein comprises 82% of the protein fraction of milk, compared to 18% for whey. Casein is commercially available primarily as sodium caseinate, potassium caseinate, and calcium caseinate and is used in the production of infant formulas, dried skim milk, and protein powders. It is considered a high-quality protein capable of increasing amino acid levels in man as well as improving protein metabolism.

Animal Studies

Studies in animals have examined the effects of casein on liver protein synthesis and fractional synthesis rates of whole-body proteins. The effects of casein and lactalbumin on radiolabeled leucine incorporation into the liver protein of Sprague-Dawley rats were compared. More Cleucine was incorporated into the liver of rats from the casein group, indicating higher rates of liver protein synthesis. Curiously, the wet weight and total protein content of the liver was lower for the casein group than the lactalbumin group. These contradictory effects were thought to result from increased liver catabolism or an increased secretion rate of liver proteins into circulation. The casein­induced increase in liver protein synthesis may be an advantage during times of infection or illness by allowing the liver to regenerate at a higher rate.

Insulin-like growth factor-1/somatomedin C (IGF-1) is a peptide hormone produced primarily by the liver. In addition, it is also a potent stimulator of protein synthesis. Male Wistar rats fed diets differing only in protein content had significantly higher levels of IGF-1 on a casein diet compared with rats fed gluten- or protein-free diets. Casein has also been shown to increase levels of IGF-1 when infused into pregnant ewes and steers and affect IGF-1 receptor levels of various tissues in rats. The casein-fed rats also had significantly greater rates of whole-body protein synthesis. These results lend some support to the previously discussed findings of James and Treloar that showed greater levels of liver protein synthesis with reduced liver weights in rats. Previous work has also shown that casein can stimulate the hepatic content of mRNA species of IGF-1 By stimulating the liver to

produce IGF-1, casein may exert an indirect effect on protein synthesis.

Casein may also affect IGF-1 levels by increasing IGF-1 absorption from the gastrointestinal tract. The survival profiles of a bolus of 1-labelled IGF-1 (8.6 ng) in vivo in various ligated gut segments of fasted adult rats was investigated. IGF-1 administered orally is rapidly proteolyzed and loses its bioactivity. However, when administered with casein, IGF-1 structural integrity and receptor binding activity in both stomach and duodenum fluids were maintained. IGF-1 uptake via endocytosis by enterocytes may allow the safe transport of unaltered IGF-1 into the blood. Casein has a slow gastric emptying rate and long gastrointestinal transit time, and therefore may allow enterocytes to endocytized IGF-1.

Casein may modulate IGF-1 levels by three separate pathways by increasing

(a) Amino acid availability and therefore modulating skeletal muscle protein synthesis and accretion through an autocrine or paracrine IGF-1 influence

(b) Absorption of IGF-1 from the GI tract

(c) Liver production of IGF_1

There are some problems with directly applying these data. The research on animals using casein infusions is based on the introduction of undegraded proteins into the GI tracts of these animals. Normally, these proteins would have undergone hydrolysis and the positive effects on IGF-1 may be lost. However, oral feeding studies on rats do demonstrate that casein can exert positive effects on IGF-1 levels. But the positive effects of casein on IGF-1 do not steadily increase. l96 Initially, casein administration increases plasma and muscle levels of IGF-1, but levels return back to baseline after 14 days. Another important point to consider is that these studies have all compared casein (an animal protein) with either a plant protein or a protein-free diet. The effects of casein on IGF-1 may also be due to the presence of additional EAAs. Future research comparing casein. whey, specific milk protein isolates, and their combinations is needed to elucidate the specific mechanisms involved. The presence of other bioactive fractions in casein may also indicate that either the individual fractions themselves or some combination mediate the indirect effects of casein on protein synthesis.

Human Studies

The effects of amino acid mixtures simulating casein and hydrolysates of casein on absorption after oral or jejunal administration. This work supports similar work done on whey protein, indicating that hydrolysates are absorbed better than their amino acid counterparts. Additional work examined the effects of casein on postprandial amino acid responses and on insulin and glucagon. The most recent research on casein focused on the delayed gastric emptying time and impact on protein synthesis

Research on healthy men and women agrees with research on animals that casein has a slow gastric emptying time. This delay results in elevated plasma amino acid concentrations up to 300 minutes postingestion. The significance of this effect is exemplified by marked differences in protein metabolism compared with whey. Casein protein ingestion results in a slight increase in protein synthesis, moderate increase in protein oxidation, and large decrease in protein breakdown. This profile results in a more positive protein balance compared with whey. This effect may be lost if casein oligopeptides are given in place of whole casein protein.

Safety and Toxicity

Casein, like any protein, has the potential to induce allergic reactions in some individuals. This is more of a concern for infants receiving formulas than adults. A more practical concern for adults is the potential hypercholesterolemic effects of casein and data from animal studies on the potential carcinogenic effects of cooked or heated casein So, individuals with hypercholesterolemia or those consuming high saturated fat diets should use casein products cautiously. Long­term research demonstrates similar side effects in rats fed semipurified diets containing either casein or soy proteins.

However, a recent study demonstrated that a casein protein diet produced a dramatic drop in Lp(a) levels, thus potentially decreasing cardiovascular risk. Also, if casein has deleterious effects on blood lipids and tumor formation, then one would speculate that heavy milk drinkers would suffer from a malady of health problems. Clearly, this is not the case.