Each Maasai tribesman in Africa ordinarily consumes 4–5 liters of fermented whole milk per day in addition to substantial quantities of meat. In spite of this diet high in saturated fat and cholesterol, the Maasai have low serum cholesterol levels and a very low incidence of clinical coronary heart disease. In studying this paradox, Mann and co-workers serendipitiously discovered that there is apparently a milk factor (MF) in the fermented milk responsible for the low serum cholesterol levels of the Maasai. A hypocholesteremic effect of fermented whole and skim milk was subsequently confirmed on American volunteers, each consuming 2–4 liters per day. Administration of radioactive acetate to human subjects on the fermented milk diet indicated that cholesterol biosynthesis was inhibited by MF. In later studies with human volunteers, English workers demonstrated a hypocholesteremic effect of unfermented whole and skim milk when consumed at a level of about 2 liters per day per caput for 2 weeks. Although the MF apparently exists in unfermented milk, there are suggestions that its concentration is slightly higher in fermented compared to unfermented milks. A hypocholesteremic effect of milk has also been demonstrated in rats by several researchers. Even though the identity of the MF is unknown at this time, it has been suggested that it may be 3-hydroxy-3-methylglutaric acid (HMG) and/or orotic acid. It is not known whether HMG occurs in cow's milk, but HMG is known to inhibit the rate limiting enzyme in cholesterol biosynthesis, HMG-CoA-reductase. Orotic acid does occur in cow's milk (73–122 mg/liter), and it has marked effects on lipid metabolism in rats. The hypolipemic action of orotic acid in rats is accompanied by induction of a fatty liver.
Comparison of Rat Hepatic Cholesterol Biosynthesis During Skim Milk Versus Whey Permeate Ingestion
