IX. EFFECTS OF DEFICIENCY 373 



However, observations indicating that factors other than the absohite 

 level of cholesterol in the blood may contribute to the production of 

 atherosclerosis leave open the possibility that inositol could function as a 

 therapeutic or prophylactic agent in man, not necessarily by its effect on 

 the concentration of cholesterol but in some other manner not yet defined, 

 for example, by regulating the cholesterol : phospholipid ratio in the blood. 

 Thus, Ladd et al.^^ found that atherosclerosis experimentally produced in 

 rabbits by the feeding of cholesterol was accompanied by considerable in- 

 crease in the concentration of cholesterol and only a slight increase in 

 the phospholipid level in the blood. These investigators observed that the 

 intravenous administration of Tween 80 to animals fed cholesterol increased 

 the blood phospholipids to levels that were as high or higher than the cor- 

 responding cholesterol levels, and decreased both the incidence and the 

 severity of the atherosclerosis. Several other workers also have emphasized 

 the importance of the relative levels of phospholipids and cholesterol. ^^"^^ 

 Duff and Payne^^ in their formulation of the pathogenesis of experimental 

 cholesterol atherosclerosis in the rabbit have stated the opinion that 

 instability of cholesterol in the blood rather than hypercholesterolemia 

 per se is the general condition responsible for the deposition of cholesterol in 

 the arterial walls. Duff and Payne considered the interrelations of the 

 lipids to be more important for their stability than is their relation to the 

 serum protein. In their experiments on normal and alloxan -diabetic rabbits 

 that were fed cholesterol, they found, as had Ladd, Kellner and Correll, 

 that the elevation of phospholipids w^as the important factor for the 

 stability of serum cholesterol, with a minor effect being exerted by the 

 neutral fats. Observations along similar lines by Ahrens and Kunkel^'' 

 indicate that the clarity of sera of high lipid content is related closely to 

 proportional elevation of the phospholipids; conversely, "milkiness" is 

 present in such sera when the relative concentrations of phospholipids are 

 low. Ahrens and Kunkel considered the concentration of serum phospho- 

 lipids available for complex formation with serum proteins to be an im- 

 portant factor in determining the size of the lipid particles in the serum. 

 More recently, Pollak^^ has emphasized the role of albumin in the pro- 

 tection of the blood vessels by its ability to stabilize cholesterol. Leinwand 

 and Moore^^ noted that the administration of a total of 3 g. of inositol daily 



" A. T. Ladd, A. Kellner, and J. W. Correll, Federation Proc. 8, 360 (1949). 



62 J. P. Peters and E. B. Man, J. Clin. Invest. 22, 707 (1943). 



63 T. Leary, Arch. Pathol. 47, 1 (1949). 



" M. M. Gertler and S. M. Garn, Science 112, 14 (1950). 



65 A. Steiner, Geriatrics 6, 209 (1951). 



66 G. L. Duff and T. P. B. Payne, J. Exptl. Med. 92, 299 (1950). 



67 E. H. Ahrens and H. G. Kunkel, /. Exptl. Med. 90, 409 (1949). 



68 O. J. Pollak, Geriatrics 6, 183 (1951). 



69 I. Leinwand and D. H. Moore, Am. Heart J. 38, 467 (1949). 



