This paper may at first sight appear to be too detailed and even boring. Far from it.
Cholesterol and coronary heart disease is such an important topic. Our understanding of the place of diet owes much to the patient meticulous studies of Grundy, Brown and Goldstein , Ahrens , Miettinen and others . Never easy reads but slowly an understanding of the complex process of cholesterol metabolism has emerged.
Always the question was being asked what if.
The studies are long winded , on volunteers in special metabolic areas and required much of the subjects and their studiers.
I t is of great interest to me to see that Tatu Miettinen is still publishing relevant work.
Apo E phenotypes E2, E3 and E4 are involved in the homeostasis of cholesterol metabolism, in its elimination as bile acids, in the removal of chylomicron remnants and in the hepatic clearance of dietary fat.
In addition, apo E phenotypes and cholesterol absorption efficiency are interrelated, so that the E4 isoform is associated with enhanced and e2 iso-form with low cholesterol absorption efficiency.
Interrelationship of apo E phenotype% with cholesterol absorption may in fact be a reason for the respective high and low levels of serum cholesterol. However, the association between apo E phenotypes and serum cholesterol level seems to be dependent on the amount of dietary fat and cholesterol.
Miettinen and colleagues has previously shown that during ad libitum home diet (HD) with high fat and cholesterol intake (38 % energy (E%)/d and 574mg/d, respectively), a positive association between apo E phenotypes and cholesterol absorption efficiency.
But not when the intakes of fat and cholesterol were reduced.
During low fat and cholesterol intake , the absorption efficiency and synthesis of cholesterol were apo E dependent, vanishing, however, after four-fold increase in cholesterol intake..
Accordingly, it seems evident that the interplay between apo E phenotypes and cholesterol metabolism is dependent on the dietary amount of cholesterol and fat.
apo E phenotype regulates the sensitivity of serum total cholesterol (TC) and LDL-cholesterol (LDL-C) levels in response to the amount of dietary cholesterol and fat..
From among small amounts of non-cholesterol sterols in serum and especially in LDL particles the most important are dietary phytosterols, cholestanol, a metabolite of cholesterol, and cholesterol precursor sterols..
In steady-state conditions, the non-cholesterol sterols reflect cholesterol metabolism such that cholestanol and the phytosterols campesterol and sitosterol reflect positively the fractional cholesterol absorption.
Whereas the cholesterol precursor sterols lathosterol and desmosterol parallel the changes in cholesterol synthesis and the activity of hepatic HMG-CoA reductase under normal conditions.
Nissinen, Gylling and Miettinen 2008 Effects of dietary cholesterol and fat on serum non-cholesterol sterols according to different apolipoprotein E subgroups among Healthy men. British Journal Nutrition vol 100. 373-379
- Martin Eastwood