Effects on HDL Cholesterol

Nicotinic acid (5.18), and related derivatives such as pyridylcarbinol (5.19), xanthinol nicotinate (5.20), acipimox (5.21), given in large doses, influence the lipoprotein ratio, decreasing the concentrations of very low and low-density lipoprotein, but have no effect on HDL-cholesterol complexes. Acipimox (5.21) is a new pyrazine derivative that is 20 times more active than nicotinic acid. When first administered, the use of these agents is associated with flushing and hypotension. 

Other dietary interventions or diet supplements may be useful in certain patients with lipid disorders. Increased intake of soluble fiber in the form of oat bran, pectins, certain gums, and psyllium products can result in useful adj unctive reductions in total and LDL cholesterol, but these dietary alterations or supplements should not be substimted for more active forms of treatment. Total daily fiber intake should be about 20 to 30 g/day, with about 25%, or 6 g/day, being soluble fiber. Studies with psyllium seed in doses of 10 to 15 g/day show reductions in total and LDL cholesterol ranging from about 5% to 20% They have little or no effect on HDL cholesterol or triglyceride concentrations. These products also may be useful in managing constipation associated with the bile acid sequestrants. Psyllium binds cholesterol in the gut but also reduces hepatic production and clearance. Fish... 

Despite seemingly positive lipid effects (decreased total and LDL cholesterol, neutral effect on HDL cholesterol, but slightly increased triglycerides) with SERMs, beneficial cardiovascular effects have not yet been clinically demonstrated. Coronary and cerebrovascular outcomes as well as safety end points were similar to placebo in the 4-year MORE trial, even within the first year. ... 

In a long-term follow-up of the Coronary Drug Project, Canner et al. (54) found in 8,341 men with established CHD that treatment with niacin resulted in an 11% relative risk reduction for mortality compared with placebo. Interestingly, despite beneficial effects on HDL cholesterol levels, treatment with estrogen was halted early in this trial for an increase in adverse effects and outcomes (55). 

Clinical trials involving mixed nuts have been conducted in six countries Australia, Canada, Israel, India, New Zealand, and the United States [61-67]. In the studies that reported blood lipid values, the nut diets significantly reduced total cholesterol from 7% to 25% and low-density lipoprotein (LDL) cholesterol by 10%-33%. No studies found any significant effect on HDL cholesterol, and two found a significant decrease in triacylglycerols (TAG) [63,66]. Furthermore, both the Lyon Heart Study and the Indo-Mediterranean Diet Study showed a decrease in overall mortality and cardiovascular mortality [45,46]. 

The first Australian study involved 16 normolipidemic men in a consecutive, supplemental field study that lasted for three 3-week dietary periods [61]. During the first 3 weeks, subjects consumed a reference diet that included a background diet supplemented with SOg/day of peanuts, 40g/day of coconut, and SOg/day of a coconut confectionary bar. During the second 3 weeks, subjects consumed the background diet supplemented with almonds (84g/day) and during weeks 7-9, subjects consumed the background diet supplemented with walnuts (68g/day). Compared to the reference diet, the almond diet lowered total cholesterol by 7% and LDL cholesterol by 10%, and the walnut diet lowered total cholesterol by 5% and LDL cholesterol by 9%, with no significant effect on HDL cholesterol or TAG. 

Due to its effect on HDL cholesterol it has been suggested that moderate alcohol consumption may be protective against coronary artery disease. In order to test the effect of alcohol on Apo A-I containing particles we have measured LpA-I and LpA-I A-II in plasma from 350 male subjects matched for age and clinical data. These subjects have been divided into five groups according to their alcohol consumption. The results confirm that alcohol consumption increases HDL cholesterol by 31%, but more remarkable is the fact that alcohol increases LpA-I A-II particles, while it decreases LpA-I particles (Fig. 3). Thus, the increase in HDL cholesterol upon alcohol consumption reflects the increase of LpA-I A-II, hiding the decrease in LpA-I, the lipoprotein particles probably involved in cholesterol reverse transport. 

This experience is worth revisiting. Does it suggest that such large effects on HDL cholesterol cannot overcome the adverse effects of a modest increase in blood pressure Does that itself cast some doubt on the HDL hypothesis, or will other inhibitors of cholesterol ester transfer protein (CETP) reveal problems not associated with blood pressure Several major companies are advanced in their trials of CETP inhibitors. One, anacetrapib, has been found to be free of the mineralocorticoid-related blood pressure effects and is equi-potent with torcetrapib and another compound already in a large outcome trial. These inhibitors bind CETP to HDL and there are differences between the compounds to the extent of the reversibility of the binding [SEDA-32, 816]. 

A daily intake of 25 and 30 g of GA for 21 to 30 days reduced total cholesterol by 6 and 10.4%, respectively (Ross et al., 1983, Sharma 1985). The decrease was limited only to LDL and VLDL, with no effect on HDL and triglycerides. However, Topping et al. (1985) reported that plasma cholesterol concentrations were not affected by the supply of GA, but triglyceride concentration in plasma was significantly lower than in controls. 

The predominant effects of fibrates are a decrease in triglyceride levels by 20% to 50% and an increase in HDL cholesterol levels by 9% to 30% (Table 9-8). The effect on LDL cholesterol is less predictable. In patients with high triglycerides, however, LDL cholesterol may increase. Fibrates increase the size and reduce the density of LDL particles much like niacin. 

Brousseau ME, Schaefer EJ, Wolfe ML,etal. Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol. N Engl J Med 2004 350 1505-15. 

Ordovas JM, Corella D, Cupples LA et al. Polyunsaturated fatty acids modulate the effects of the APOA1 G-A polymorphism on HDL-cholesterol concentrations in a sex-specific manner The Framingham Study. Am J Clin Nutr. 2002, 75 38 16. 

Raloxifene Like tamoxifen, which is also a SERM (see p 266), raloxifene s [ra LOCKS ih feen] actions are mediated through the estrogen receptors, and it has both estrogenic and antiestrogenic effects. Its clinical use is based on its ability to decrease bone resorption and overall bone turnover. However, unlike estrogen and tamoxifen, it apparently has little to no effect on the endometrium, and therefore may not predispose to uterine cancer. Raloxifene lowers total cholesterol and LDL in the serum, but has no effect on HDL or triglycerides. [Note Whether the latter... 

What about the choices between carbohydrates, monounsaturated fatty acids, and PUFAs Studies on monounsaturated fatty acids versus carbohydrates have shown that monounsaturated fatty acids provoke a decrease in plasma TGs and an increase in HDL-cholesterol, with not much difference in effect on LDL-cholesterol. Studies on PUFAs versus carbohydrates have revealed that PUFAs result in lower LDL-cholesterol, with not much difference in effect on plasma TGs or HDL-cholesterol. 

Red ginseng powder may be useful in hyperlipidemia it was shown to decrease triglycerides as well as increase high-density lipoprotein (HDL) in a pilot study (50). A previous rat study lends validity to ginseng s ability to decrease triglyceride levels (16), but a study in patients with diabetes showed no effect on total cholesterol, low-density lipoprotein (LDL), HDL, or triglyceride levels (18). 

No effects on serum cholesterol levels were noted in workers chronically exposed to 10-30 ppm carbon disulfide (Hemberg et al. 1971), and several studies failed to observe increased serum cholesterol levels in workers exposed to carbon disulfide at concentrations below 20 ppm. In an occupational study, 35 workers chronically exposed to carbon disulfide concentrations ranging from 6.4 to 12.8 ppm for 5-20 years exhibited a statistically significant reduction in blood cholesterol levels a nonsignificant reduction in total lipid levels was also observed. This study is of limited value because of the small sample size and the likelihood of concurrent exposure to other chemicals (Sidorowicz et al. 1980). Another study of 70 men exposed to carbon disulfide in a viscose plant who were matched to unexposed men working in a different division of the plant found no statistically significant differences in blood lipid profiles (total cholesterol, HDL-Ch, and triglycerides) (Franco et al. 1982). Carbon disulfide concentrations were less than 11.2 ppm from 1972 to 1979. Workers (n=420) in a rayon filament factory chronically exposed to carbon disulfide... 

HDL cholesterol can be reduced, because progestins attenuate some of the positive effects of estrogens on HDL cholesterol. However, estrogen-induced benefits on LDL cholesterol are retained. 

AGls have no significant effect on total and LDL-cholesterol [38]. However, recently published investigations in patients with IGT analyzing LDL-subfractions reveal a decrease in small dense LDL [39]. No significant effects have been shown on HDL-cholesterol in the STOP-NIDDM study... 

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