Niacin, cholesterol-lowering effects

Nicotinic acid (niacin) was first shown to lower serum cholesterol levels over 40 years ago (1955). This activity is not related to its vitamin functions (nicotinamide does not share its action). At daily doses of 3 g niacin s hypocholesterolemic effects are about equivalent to clofibrate. In addition to lowering triglycerides, it can also raise HDL levels. Unfortunately, at these high doses nicotinic acid can produce intense flushes and itching, resulting in poor patient compliance. Circumventing the problem with potential pro-drugs such as nicotinyl alcohol, fructose tetranicotinate, and others were not very successful. 

Niacin Tolerability Large doses of niacin (nicotinic acid) effectively lower serum cholesterol levels, reduce LDL, and raise HDL see Chapter 35). However, niacin is tolerated poorly because it induces intense flushing. This flushing is mediated by a release of prostaglandin Dj from the skin, which can be inhibited by treatment with aspirin. 

There is some evidence that niacin can reduce the incidence of cancers of the mouth and throat. Niacin has been used to protect (3-cells in the pancreas in insulin-dependent diabetics and has been reported to increase insulin sensitivity. The effects of niacin in lowering cholesterol and low density lipoprotein have been studied extensively. High doses up to 1 g per day are required but the evidence for effectiveness is not wholly conclusive. There is some evidence that high doses of niacin improve survival rates in HIV infection. In conjunction with tryptophan, niacin has been used to treat depression. 

Combination drug therapy is an effective means to achieve greater reductions in LDL cholesterol (statin + ezetimibe or bile acid resin, bile acid resin + ezetimibe, or three-drug combinations) as well as raising HDL cholesterol and lowering serum triglycerides (statin + niacin or fibrate). 

These agents act in a complementary fashion to normalize cholesterol in patients with severe disorders involving elevated LDL. The effects are sustained, and little compound toxicity has been observed. Effective doses of the individual drugs may be lower than when each is used alone for example, as little as 1-2 g of niacin may substantially increase the effects of the other agents. 

Niacin (but not niacinamide) is also indicated in hyperlipidemia to lower uiglycerides and cholesterol. Triglycerides. VLDL.S, and LDLs are reduced HDLs are increased. The exact mechanism is not known. Because niacin at high doses has a direct vasodilatory effect believed to be mediated through the prostaglandins, the dose required (1 to 3 g 3 times daily) often limits the usefiilne.ss. 

Niacinamide was formulated to be a form of niacin that does not cause flushing of the skin. However, it has little effect on lowering cholesterol. 

Millions of people in the world suffer from cardiovascular disease, and it is a leading cause of death in both men and women. Elevation in plasma low-density lipoprotein (LDL) cholesterol levels is a major risk factor for myocardial infarction (heart attack) in these patients. Drugs to reduce dyslipidemia have included niacin and the fibrate class, but each of these has clinical limitations, such as low efficacy or toxic side effects. The development of HMG-CoA reductase inhibitors, or statins, has had an enormous clinical impact on the treatment of heart disease and prevention of heart attack, and these are taken by tens of millions of patients worldwide [1]. One of the first such drugs, lovastatin, was discovered in the 1970s as a fungal natural product [2] and lowered lipid levels in animals and healthy volunteers. Problems with the development of another early statin, compactin, halted advancement of lovastatin to regular clinical use until the late 1980s. Since then. 

Cohen in an eight-year appraisal of clinical use of dextro-thyroxine concluded that D-T4 is an effective agent in lowering blood cholesterol. He cautioned, however, against its use in patients with coronary heart disease. A comparative study with clofibrate, dextrothyroxine and niacin indicated that all three ccmpounds lowered serum cholesterol . ... 

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