"normal" range of serum cholesterol, which is associated with a high incidence of atherosclerosis in this country.

Cholesterol and the Diet

In view of the above associations between serum cholesterol and the incidence of atherosclerosis, there has been considerable study of the effect of dietary alterations on cholesterol level in humans. The assumption is generally made that reduction in serum cholesterol is beneficial and elevation detrimental in clinical atherosclerosis. This assumption has little experimental or observational support at this time.

Severe restriction of fat intake will generally reduce the level of serum cholesterol, especially if this is initially elevated. This effect is minimal or absent in familial hypercholesterolemia, but present in familial hyperlipemia. Hypercholesterolemia has been remarkably difficult to produce in man, even by high fat, high cholesterol feedings.

Groen's report (8) that different fats have different effects on serum cholesterol has been repeatedly confirmed. Unsaturated fats such as corn, safflower and cottonseed oil produce significant falls in serum cholesterol when substituted for an equal quantity of animal fat in the diet. Addition of a quantity of vegetable oil to the usual animal fat intake is generally ineffective. The drop in serum cholesterol is accompanied by an increased fecal loss of cholesterol and its byproducts. Though an increased intake of unsaturated fats is often advocated therapeutically for patients with atherosclerotic vascular diseases and prophylactically for the population in general, there is as yet no objective evidence that it accomplishes these aims.

Other Factors Influencing Cholesterol Level

Recent studies (9) have shown a relationship between blood cholesterol and mental stress, the cholesterol level undergoing remarkable rises with such stress. There is considerable individual variation, more susceptible individuals showing rises within hours (10). Friedman has also reported increased blood coagulability during such periods of stress (9).

The role of exercise is more discussed than investigated. Epidemiologic studies suggest that more active groups have less coronary atherosclerosis than sedentary groups (11). Increased exercise has been shown to prevent the rise in blood lipid with increased caloric intake.

Weight loss has been shown to reduce blood cholesterol levels in those with initially elevated levels (12).

lo

A number of drugs such as nicotinic acid in high doses, (13) triparanol (MER 29) (14), and sitosterol (15) have been effective in lowering serum cholesterol.

Atherosclerosis and Thrombosis

Atherosclerosis has long been felt to increase the tendency for blood clotting in the immediate vicinity of the lesion. Duguid (16) feels, from histologic evidence, that thrombosis may play a more primary role, atherosclerosis being initiated by deposits of fibrin on the arterial intimal surface.

Prospective Studies in Man

Several prospective studies of large population groups are under way (17, 18, 19), and are of extreme importance, not only in testing in a more refined way the conclusions drawn from epidemiologic studies, but in clarifying the usefulness of certain techniques of earlier diagnosis of coronary disease. Thus far these have reaffirmed the importance of heredity, obesity, hypertension and hypercholesterolemia as predisposing factors in atherosclerosis.

Prospective studies of the effectiveness of certain dietary programs such as low fat intake, high unsaturated fat intake, or hypocholesterolemic drugs on large population groups are infinitely more difficult, but one such study has begun (20). The importance and necessity of such studies is obvious.

Therapy of Atherosclerosis

There is general agreement that overnutrition should be corrected in any recognized disease related to atherosclerosis. Most agree that this should be done by restriction of fat intake. The beneficial effect of moderate exercise is now recognized. The use of unsaturated fats, nicotinic acid, sitosterol and other hypocholesterolemic agents is widely advocated, but at present this is based on feeling rather than evidence.

The long term use of anticoagulant drugs has been reported as beneficial in coronary arterial disease and in certain cases of cerebral vascular disease (intermittent cerebral ischemic attacks, cerebral thrombosis). On the basis of present evidence, the use of this form of therapy in coronary artery disease seems justifiable, especially during the first year after onset of symptoms. The risk of hemorrhage seems too great to warrant its use in cerebral vascular disease (21).

The use of heparin, not as an anticoagulant, but as a lipid clearing factor, is being tested, but requires more evaluation before valid conclusions can be drawn.

Direction of Current Research and Current Research Needs

The enormous volume of excellent basic work on the biochemistry and morphology of atherosclerosis is noteworthy. The pathways of synthesis and breakdown of cholesterol and regulating mechanisms are receiving much attention. The transport and metabolic handling of lipid is also being intensively studied. The many methodological advances in the field are continually providing new and interesting approaches to the biochemistry of lipids.

There is a conspicuous lack of well controlled, long term studies testing in man the numerous hypotheses suggested by more basic research, and testing in patients the effectiveness of various therapeutic recommendations. This type of investigation is always difficult to carry out, but in the final analysis the proof of any hypothesis relative to atherosclerosis in man must rest on such evidence.

Such research not only requires financial support for success, but requires years for completion, much of which is spent in collecting and recording data, activities not calculated to increase the academic rank and stature of a young investigator. Some adequate means must be provided to counterbalance these disadvantages.

One of the basic problems in research on man is the lack of techniques for assessment of the degree of atherosclerosis in a given individual. At present atherosclerosis can rarely be detected until some vital structure is deprived of blood supply. Once detected, the only means available for assessment of the effect of therapy is comparison of incidence of new atherosclerotic complications and mortality in a treated versus a control group. Cineangiographic and other techniques must be developed to provide more accurate tools for early detection and grading of atherosclerotic lesions, so that the effect of therapy on individual lesions can be evaluated.

Existing Research Opportunities and Support

Research support for relatively short term studies in man and experimental animals and for more basic biochemical and morphologic studies is fairly readily available, though a bigger outlay of funds would doubtlessly increase the rate of accumulation of data. The need for well controlled long term studies in man has already been cited. The chief need in this area is for adequate long term support combined with available, stable, cooperative population groups. Mental institutions, prisons and domicilliary homes are likely sites for such research. Because of the nature of such research, it will probably be necessary to provide the personnel conducting it with time and facilities for other more short term research. It is possible that the increasing pool of well trained practicing physicians could be organized into cooperative groups, each physician testing two well designed therapeutic protocols in selected patients with atherosclerotic disease.

REFERENCES

1. Anitschkow, N. Cited by Groen, J. and Van Der Heide, R. M. Atherosclerosis and Coronary Thrombosis. Medicine 38: 1-23, 1959, p.. 3.

2. Dauber, D. V. and Katz, L. N. Cited in Experimental Atherosclerosis. Katz, L. N. and Stamler, J. 375 pp. Springfield, Illinois: Charles C. Thomas, 1953, p. 123.

3. Kendall, F. E. Quoted by Heath, F. K. Cholesterol Metabolism and Arteriosclerosis. Am. J. Med. 6: 103–124, 1949, pp. 110-113.

4. Reiser, R., Sorrels, M. F. and Williams, M. C. Influence of high levels of dietary fats and cholesterol on atherosclerosis and lipid distribution in swine. Circ. Res. 7: 833-846, 1959.

5. Cox, G. E., Taylor, C. B., Cox, L. G. and Counts, M.

Cited in Atherosclero

sis in Rhesus Monkeys. Nutrition Rev. 17: 55–57, 1959.

6. Groen, J. and Van Der Heide, R. M. Atherosclerosis and Coronary Thrombosis. Medicine 38: 1-23, 1959.

7. Katz, L. N., Stamler, J. and Pick, R. Nutrition and Atherosclerosis. 146 pp. Philadelphia, Pennsylvania: Lea and Febiger, 1958.

8. Groen, J., Tjiong, B. K., Kamminga, Chr. E., and Willebrands, A. F. Cited by Groen (6), p. 5.

9. Friedman, M., Rosenman, R. H., and Carrol, V. Changes in the serum cholesterol and blood clotting time in men subjected to cyclic variation of occupational stress. Circulation 17: 852-861, 1958.

10. Peterson, J. E., Wilcox, A. A., Haley, M. I., and Keith, R. A. Hourly variation in total serum cholesterol. Circulation 20: 752, 1959.

11. Morris, J. N., Heady, J. A., Raffie, P. A. B., Roberts, C. G., and Parks, J. W. Coronary heart disease and physical activity of work. Lancet 2: 1053-1057, 1953.

12. Walker, W. J., Lawry, E. Y., Love, D. E., Mann, G. V., Levine, S. A. and Stare, F. J. Effect of weight reduction and caloric balance on serum lipoprotein cholesterol levels. Am. J. Med. 14: 654-664, 1953.

13. Berge, K. G., Achor, R. W. P., Christensen, N. A., Power, M. H. and Barker, N. W. Hypercholesterolemia and Nicotinic Acid: Long Term Study. Circulation 20: 671, 1959.

14. Hollander, W., Chobanian, A. V., and Wilkins, R. W. Effects of an inhibitor of cholesterol biosynthesis, triparanol (MER-29), in subjects with and without coronary artery disease. Circulation 20: 713-714, 1959.

15. Best, M. M., Duncan, C. H., Van Loon, E. J., Wathen, J. D. The effects of sitosterol on serum lipids. Am. J. Med. 19: 61-70, 1955.

16. Duguid, J. Pathogenesis of atherosclerosis. Lancet 2:925, 1949.

17. Dawber, T. R., Moore, F. E. and Mann, G. V. Coronary heart disease in the Framingham Study. Am. J. Public Health 47: 4-24, 1957.

18. Doyle, J. T., Heslin, A. S., Hilleboe, H. E., Formel, P. F. Early diagnosis

of ischemic heart disease. New Eng. J. Med. 261: 1096-1101.

19. Thomas C. B. Familial and epidemiologic aspects of coronary disease and hypertension. J. Chronic Dis. 7: 198–208, 1958.

20. Veterans Administration Cooperative Study on Atherosclerosis. Effect of high unsaturated fat intake. Los Angeles V. A. Center, Los Angeles, Calif.

21. Veterans Administration Cooperative Study on Atherosclerosis: Anticoagulants in Cerebral Vascular Disease, preliminary data.

Nutritional Requirements of the Aged

Existing Knowledge

By BENJAMIN T. BURTON, PH. D.5

Sound nutrition in the elderly is not fundamentally different from normal nutrition in the mature adult. However, certain characteristics inherent in the aging process and unique facets to geriatric

nutrition.

Physiologic Factors

Inadequate dentition and ill-fitting dentures contribute to undernutrition in old age. Poor dentition results in inadequate preparation of food for digestion and leads to a gradual avoidance of foods which require thorough mastication. Thus, important food items like meats and the bulk-forming fruits and vegetables are gradually and progressively bypassed.

With advancing age, there is a diminishing sensitivity to taste and smell which interferes with the normal pleasures of eating; a decrease in physical activity also serves to diminish individual appetites. Secretion of gastric hydrochloric acid and of digestive juices in general also tends to decrease. Thus, digestion and absorption of essential nutrients (such as iron) may not be optimal in many elderly people. In many instances, fatty foods are not well tolerated because of biliary impairment. Thus, low stores of fat soluble vitamins are not uncommon, either because of voluntary abstention from fats (and the associated fat soluble vitamins) or because of poor intestinal absorption.

Constipation is frequent among the elderly. It is partially due to an atonic intestinal musculature, but decreased physical activity, an inadequate fluid intake and avoidance of bulk-forming fruits and vegetables underlie much of it.

The nitrogen balance tends to become negative as dietary protein intake decreases while tissue protein catabolism continues unabated; the ill effects of hypoproteinemia-retarded bone and wound repair, predisposition to anemia, and decreased resistance to infection-are thus more conspicuous in advanced age.

An inadequate calcium intake and negative nitrogen balance are probably contributing factors (together with decreased secretion of anabolic hormones, and skeletal disuse) to the high incidence of osteoporosis among the aged.

Concurrent with a drop in metabolic rate, there is a decrease in physical activity in later years, thus diminishing considerably the total caloric requirement of the individual. If the eating habits of