March 1, 1961
Margaret Albrink, Yale: Elevated Triglycerides (TG) - not cholesterol - were associated with increased risk of heart disease. Low-fat, high-carb diets raised TG. Albrink: Ancel Keys' supporters attacked me, "They were so angry!"
LIPOPROTEIN PATTERN AS A FUNCTION OF TOTAL TRIGLYCERIDE CONCENTRATION OF SERUM
MD Conf, May 1961: Margaret Albrink, Yale: Elevated Triglycerides (TG) - not cholesterol - were asso w/ increased risk of heart disease. Low-fat, high-carb diets raised TG. Albrink: Ancel Keys' supporters attacked me, "They were so angry," & the science bullies prevailed.
The occasional occurrence of lactescent or milky serum in patients with certain diseases caused interest and speculation at least as long ago as 1799 when Mariet described turbid sera in some patients with diabetic acidosis (1). The lightscattering fat particles or chylomicrons causing lactescence are present in modest numbers after a fat meal but become scarce in normal postabsorptive sera. In certain pathological states, however, chylomicrons occur in excessive numbers, giving rise to a characteristic milky appearance of the sera. In a previous study, lactescence was reported to be directly proportional to the total triglyceride concentration in serum (2). Turbidity was invariably present when total triglyceride fatty acid concentration exceeded 20 mEq per L. As triglyceride concentration increased further, a progressively greater proportion of cholesterol and phospholipids also occurred in the particulate lipid fraction which could be readily removed by flotation of unaltered serum at moderate speeds in the ultracentrifuge. Serum lipids are now known to exist in a spectrum of lipoproteins of varying density, from very low density particulate chylomicrons composed chiefly of triglycerides, through various classes of low density lipoproteins relatively rich in cholesterol, to high density lipoproteins in which phospholipids are prominent (3). Interest in various classes of low density lipoproteins has been stimulated because of their possible role in the etiology of coronary arterial disease (4). Studies from this laboratory (5-7) have shown serum triglyceride concentration to be intimately associated with this disease. Antonis and Bersohn have also found elevation of serum triglycerides in ischemic heart disease (8). From the known composition of very low density lipoproteins, it might be inferred that their presence in abnormally high concentrations would be associated with increased concentration of total serum triglycerides. The present study was undertaken to learn whether total triglyceride concentration might determine not only the fraction of lipids present in chylomicrons but also the partition of lipids among the various low density lipoproteins. At the same time the lipoprotein composition of the relatively clear subnatant fluid after removal of the chylomicron "cream" layer of lactescent sera could be determined. This clear fraction was previously analyzed in toto (2), but no analysis of lipoproteins was made.
* Supported (in part) by Grant H-3498(C2) from the National Heart Institute, Bethesda, Md., and by a grant from The James Hudson Brown Memorial Fund. This work was done during tenure of an established investigatorship of the American Heart Association.