Cancer and low levels of plasma cholesterol: the relevance of cholesterol precursors and products to incidence of cancer.

BACKGROUND: It is proposed that the mechanism responsible for the low plasma cholesterol-cancer associations reported in the literature is related to blood and tissue levels of cholesterol precursors and products, reflecting rates of cholesterol synthesis rather than the plasma cholesterol level itself. METHODS: Data have been collated from Japanese and Northern European studies on plasma levels of a cholesterol precursor, lathosterol, and one product, cholestanol, each a marker of cholesterol metabolism. Situations in which the rate of cholesterol synthesis is altered have also been examined for their relationship to cancer incidence. RESULTS: The data though minimal suggest that lathosterol and cholestanol may be higher in the blood of the Japanese compared with the Northern Europeans, despite lower plasma cholesterol levels in the Japanese. In accord with the hypothesis the Japanese have a low incidence of many cancers. Cholesterol synthesis is lowered when dietary cholesterol and fat intake are increased and incidence of cancer is increased in these states. Conversely cholesterol synthesis is raised in vegetarianism, the Mediterranean diet, pregnancy, and lactation, and incidence of some cancers is lowered. CONCLUSIONS: At least some of the variation in cancer incidence with plasma cholesterol levels and also with dietary saturated fat and cholesterol, as well as vegetarianism, the Mediterranean diet, pregnancy, and lactation, can be accounted for by their effects on the rate of cholesterol synthesis and the level of cholesterol precursors and/or products so generated.

Total glycosaminoglycans in the plasma of adults: effects of age and gender, and relationship to plasma lipids: a preliminary study.

Plasma glycosaminoglycans and lipids have been measured in the plasma of 92 fasted males and females. In the males, glycosaminoglycans correlated significantly with age (r = 0.39), triglycerides (r = 0.44), and cholesterol (r = 0.30). When the effect of age was allowed for, the significance of the correlation between glycosaminoglycans and triglycerides was maintained (r = 0.36). Glycosaminoglycan levels are higher in females than in males. The correlation of glycosaminoglycans with age in women was only marginally significant. In both men and women the effect of age is attributable principally to an increase in glycosaminoglycan concentration in those over 54 years. The only lipid fraction correlating with glycosaminoglycans in females was VLDL cholesterol (r = 0.34) and by stepwise linear regression allowing for the effect of age, this significance was retained (beta = 0.34).

Quantitative gas chromatographic measurement of glycosaminoglycan hexosamines in urine and plasma.

A method is described for the quantitative determination of urine and plasma glycosaminoglycans (GAGs) by gas chromatography of the acetylated amino sugars. GAGs were first recovered by precipitation from urine with alkyltrimethylammonium bromide and from plasma by mini-column chromatography after papain digestion. Urine samples (24) analysed for total hexosamines by gas chromatography and for uronic acid by colorimetry had a correlation coefficient of 0.85. The within-run coefficient of variation (C.V.) for nineteen samples from a pooled urine was 5.2% for total hexosamines and that for the ratio of galactosamine to total hexosamines was 3.7%. The corresponding C.V. values for twelve plasma samples from a common pool were 6.5 and 3.7%. The mean ratio of galactosamine to total hexosamine in ten pre-breakfast spot urines was 51.5%. The corresponding ratio in the plasma from twenty adolescent blood donors was 76.3% and the mean total hexosamine content of the GAGs was 47.36 mumol/l.

Urine glycosaminoglycans in a reference population: effects of age, body surface area, and postmenopausal status.

Urine glycosaminoglycans and hydroxyproline have been measured in an adult reference population containing significant numbers of those over 65 years. Urine concentrations of glycosaminoglycans remain constant into old age providing body weight is maintained and correlate significantly with body surface area. The urine ratio of glycosaminoglycans to creatinine rises markedly in women after menopause resulting in a bimodal frequency distribution. This ratio is worth further investigation as a marker of postmenopausal osteoporosis.

Red cell and hemorheological changes in multiple sclerosis.

Blood rheology in multiple sclerosis (MS) was investigated in 15 subjects with varying degrees of locomotor difficulties who were members of the local MS Society. Control data were obtained from blood samples from 25 male and 25 female normal blood donors. Whole blood viscosity was measured and blood filterability was assessed. Six MS females provided blood samples for scanning electron microscopy. Erythrocyte membrane fatty acids and phospholipids were assayed. Whole blood viscosity in MS females was higher than controls at 3 of 4 shear rates (p less than 0.001) but in MS males blood viscosity was higher only at shear rate of 1.0 s-1 (p less than 0.05). MS erythrocyte filtration rates were significantly lower than controls (p less than 0.001). Leucocyte counts in MS were greater than controls both in males (p less than 0.01) and females (p less than 0.001). MS erythrocyte morphology was greatly different from controls (p less than 0.0001) and erythrocyte membranes contained less sphingomyelin than controls (p less than 0.01) but more phosphatidylinositol plus phosphatidylserine (p less than 0.02). We conclude that, because our findings indicate an identifiable and potentially correctable abnormality, it is possible to envisage an inhibition of the progressive nature of MS, with the hope of a better prognosis for patients.

Blood lipids and lipoproteins in a rural New Zealand population.

Plasma cholesterol and triglycerides have been measured in 1202 residents of Milton, a rural town in New Zealand. Cholesterol and triglyceride concentrations in the serum lipoprotein classes of a random subgroup of the population are also reported. Mean plasma triglycerides and very low density lipoprotein (VLDL) cholesterol and triglyceride concentrations were higher for men, but mean high density lipoprotein (HDL) cholesterol concentration was higher in women. Urban-rural differences in plasma cholesterol are suggested since mean plasma cholesterol concentration in men reached a maximum in the 50-59 decade in the rural town (Milton) but the maximum for a nearby urban community was in the 40-49 decade. An evaluation of hyperlipidaemia by using arbitrary cut-off values for plasma cholesterol and triglyceride concentrations showed a prevalence of hypertriglyceridaemia in men, resulting in approximately three times as many men as women in some of the categories of hyperlipidaemia. Further, 26% of the 35-59 age group in the population had lipid risk factors for coronary heart disease.

Lecithin: cholesterol acyl transferase activity in the serum of rats fed saturated and unsaturated fats.

Groups of rats were fed diets containing either butter, beef, fat or safflower oil. After 20 or 70 days of feeding, blood was taken from the animals in a postabsorptive state. Serum lipid levels and lecithin: cholesterol acyl transferase activity were measured. Feeding the different fats did not alter serum total cholesterol levels but free cholesterol and triglycerides were significantly lower in the safflower oil-fed group. Net cholesterol esterification in vitro was also significantly depressed in the safflower oil-fed group and this was shown to be due to the inability of the lipoprotein substrate to support the reaction rather than because of low LCAT enzyme activity.

Modification of nicotinic acid and prostaglandin E1 antilipolytic action in vitro.

In epididymal adipose tissue from rats, human serum antagonizes inhibition of basal lipolysis by nicotinic acid in vitro. Under similar conditions caffeine-stimulated lipolysis was unaffected by the presence of human serum. Very low density (VLDL), low density (LDL) and high density (HDL) lipoproteins were all found to antagonize the action of nicotinic acid on basal lipolysis. VLDL also antagonized prostaglandin E1 (PGE1)-inhibition of basal lipolysis in vitro. The fat cell membrane was suggested as the site at which human serum lipoproteins antagonize nicotinic acid or PGE1 antilipolytic action on basal lipolysis in vitro.

The effect of dietary lipids on lipolysis in rat adipose tissue.

1. Rats were fed for 8 weeks on one of five diets differing in the amount of fatty acids 18:1, 18:2 and 18:3. Lipolysis, in vitro, of epididymal fat from fed and fasted rats was measured both basally and in the presence of noradrenaline with and without prostaglandin E1. 2. Lipolysis was markedly influenced by the type of dietary fat. In particular, lipolysis in adipose tissue from rats given diets rich in the fatty acid 18:3 was higher than in the rats given diets containing 18:2. 3. Results showing the effects of fasting on adipose tissue lipolysis are also presented. 4. The results are discussed in relation to the known effects of unsaturated fats on hyperplasia and protein synthesis in adipose tissue and on the possible role of prostaglandins.