Maurice M. Best

Lowering of Serum Cholesterol by the Administration of a Plant Sterol

The plant sterol, beta-sitosterol, has been administered to nine subjects on unrestricted diet. A sustained reduction of serum total cholesterol and a lowering of the ratio of cholesterol to lipid phosphorus occurred. Interference by sitosterol with the absorption of cholesterol, both dietary and that excreted into the gastrointestinal tract, is presumably responsible for this hypocholesterolemic effect. No toxic or undesirable side effects were observed. A means of studying the effects of a sustained lowering of serum cholesterol on atherosclerotic states would now seem to be available.

The effects of sitosterol on serum lipids

Abstract 1.1. The effects of the plant sterol, beta-sitosterol, on serum cholesterol, other lipids and lipoproteins have been studied. Twenty to 25 gm. of sitosterol per day was administered for prolonged periods to fourteen patients on free diets. 2.2. A sustained lowering of serum total cholesterol results from the prolonged administration of sitosterol. A concomitant reduction in serum total lipid, neutral fat and, to a lesser degree, lipid phosphorus occurs. 3.3. A trend toward lower levels of S f 3–10, 10–30 and 30–100 classes of lipoproteins occurs during sitosterol administration but this effect is less consistent than the reduction of serum cholesterol. 4.4. The effects of sitosterol are attributable to its interference with absorption of cholesterol. They are not identical with those of dietary cholesterol restriction, since sitosterol would seem to reduce absorption of cholesterol present in the bile as well as that present in the diet. 5.5. It is suggested that sitosterol interferes with cholesterol absorption by competing for esterification, a step in the transport mechanism by which cholesterol is absorbed. 6.6. The changes in serum lipids and lipoproteins resulting from sitosterol administration are in the direction generally considered desirable in atherosclerosis, and the absence of any toxic or adverse side effects permits its further study in man.

Reduction of serum triglycerides and cholesterol by ethyl p-chlorophenoxyisobutyrate (CPIB)

Abstract Ethyl p -chlorophenoxyisobutyrate (CPIB) was administered alone and in combination with androsterone to 10 patients with elevations of serum cholesterol and/or triglycerides. Serum lipid levels during the two four-month treatment periods were compared to those during a period of placebo administration of similar duration, the order of the periods being randomized. As compared to the placebo period, a mean reduction in serum triglycerides and, to a lesser extent, cholesterol occurred during the administration of both CPIB alone and CPIB with androsterone. The addition of androsterone to the CPIB did not significantly enhance the hypolipemic activity of CPIB. No adverse effect or toxicity was encountered.

MODIFICATION OF ABNORMAL SERUM LIPID PATTERNS IN ATHEROSCLEROSIS BY ADMINISTRATION OF SITOSTEROL

Excerpt The reports by Peterson that the addition of soybean sterols to experimental diets of chicks appeared to inhibit the absorption of cholesterol1and to effect a decreased incidence of atheros...

Lipid effects of a phenolic ether (Su-13437) in the rat: Comparison with CPIB☆

Abstract The effect on serum and liver lipids of rats fed 2-methyl-2-[ p -(1,2,3,4-tetrahydro-1-naphthyl)-phenoxy]-propionic acid (Su-13437), has been studied. At a concentration in the diet of 0.01% in young males and 0.05% in young females, a significant increase in wet weight of the liver was observed. A significant reduction in serum triglyceride was noted in males fed 0.002 % and in females fed 0.05 %. Su-13437 did not significantly reduce mean serum cholesterol in any of the groups and at 0.25 produced a significant increase. At 0.25 % Su-13437 resulted in reduced liver triglyceride concentration in both males and females. It appears that somewhat less than one-fifth as much Su-13437 as CPIB is required to produce similar degrees of hepatomegaly and of reduction in serum triglyceride. In addition to this quantitative difference in activity, Su-13437 and CPIB differ in respect to their effects on serum cholesterol.

Comparative Effects of Thyroxin Analogues as Hypocholesteremic Agents

L-thyroxin and four thyroxin analogues were administered to a group of hypercholesteremic euthyroid patients, the majority with arteriosclerotic heart disease, and the effects on serum total cholesterol compared. L-thyroxin and each of the analogues studied, tetraiodothyroformic acid, dimethyldiiodothyroformic acid, D-thyroxin and D-triiodothyronine, were given to four to nine patients for periods up to 10 months. At the doses employed each of the analogues resulted in a reduction in the mean level of serum cholesterol without obvious evidence of hypermetabolism or aggravation of angina pectoris or congestive heart failure. The reduced level of serum cholesterol was sustained throughout the period of hormone administration, and upon the substitution of a placebo returned to the pretreatment range. L-thyroxin, at the dose employed, also effected a modest sustained reduction in serum cholesterol but both patients with angina included in this group experienced an increase in severity of symptoms. Except for four patients who developed acneiform dermatitis, salivary gland swelling, or gastrointestinal symptoms during the administration of the formic acid analogues, no toxic or undesirable effects were observed from any of the analogues. To evaluate better the general metabolic effects of the analogues each was administered to three or more of a group of seven myxedematous patients for periods of 6 to 12 months. Given in sufficient amount all were observed to increase basal metabolic rate and to maintain a clinically euthyroid state. From these observations, it is concluded that the D-isomers of thyroxin and triiodothyronine, while not without general metabolic effects, are tolerated by the majority of euthyroid patients with coronary atherosclerosis in amounts sufficient to maintain a reduced serum cholesterol level.

Effects of L- and D-thyroxine and of thyroidectomy on tissue weights and cholesterol content of the rat

The mean concentration of cholesterol in the body of the normal male rat fed a balanced laboratory chow was 1.72 mg./Gm. body weight. Hyperthyroidism produced by the daily injection of either L-thyroxine or D-thyroxine resulted in an increase in concentration, largely from increased cholesterol concentration of the skin. Thyroidectomy had no effect on total body cholesterol. The addition of cholesterol to the diet caused an increase in cholesterol of the euthyroid rat to 2.25 mg./Gm. body weight, the greater part of the increase being in the liver. In the cholesterol-fed rat hyperthyroidism resulted in a reduced total body cholesterol, due almost entirely to a lower concentration in the liver. Thyroidectomy accentuated the accumulation of cholesterol in the liver of the cholesterol-fed rat. Hyperthyroidism resulted in hypertrophy of heart, kidneys, liver, gastrointestinal tract, lungs and spleen, relative to body weight; hypothyroidism caused a decrease in weight of these organs. These effects of the thyroid state on organ weights were not significantly influenced by the addition of cholesterol to the diet.

The status of hormonal therapy for the primary and secondary prevention of atherosclerotic coronary heart disease

E XTENSIVE EVIDENCE is available implicating hormonal derangements in the multifaetorial etiology and pathogenesis of atherosclerotie disease. It has also been repeatedly demonstrated that several hormones--including growth hormone, andrenocorticotrophic hormone, corticoids, thyroid preparations, estrogens and androsterone~tend to lower serum cholesterol-lipid]ipoprotein concentrations. 15 Since hyperlipidemia has been unequivocally shown to increase the risk of premature clinical atherosclerotic coronary heart disease 2,5a~ the concept has inevitably developed that therapy with cholesterol-lowering hormones might be effective against this disease. The purposes of this paper are to review briefly the rationale for the use of specific hormones for the primary and secondary prevention of clinical atherosclerotie disease, and to summarize the present status of investigation in this field. Although multiple hormonal influences have been demonstrated, research on therapeutic application has been almost exclusively confined to thyroid hormones and estrogens--plus recent studies on androsterone, and on the combined use of thyroid preparations and corticosteroids. This paper, therefore, is limited to a discussion of these agents.*

Effects of Sitosterol on the Cholesterol Concentration in Serum and Liver in Hypothyroidism

The effects of the administration of the plant sterol, &bgr;-sitosterol, on the elevated serum lipids of hypothyroidism and on the cholesterol content of the liver have been investigated. In patients with hypothyroidism sitosterol administration, without dietary restriction, resulted in a reduction of serum cholesterol and other lipids. In the hypothyroid rat the addition of sitosterol to the diet prevented the increase in serum lipids and in the cholesterol content of the liver which otherwise occurs on a high-cholesterol diet.

Influence of a terminal period of fasting on the serum and tissue lipid effects of ethyl chlorophenoxyisobutyrate (CPIB)

Abstract The apparent effect of ethyl chlorophenoxyisobutyrate (CPIB) on serum and tissue lipids of rats was markedly influenced by a terminal period of fasting and/or discontinuation of the drug. The significant reduction of serum triglycerides, cholesterol, and phospholipid observed during CPIB administration was no longer present 18 to 24 hours after withdrawal of the drug. The increase in liver triglycerides during CPIB administration was reversed after 24 hours withholding of both food and drug, liver triglycerides then being lower than in fasted control animals.