Niacin Augments the Benefits of Statins

Niacin for Healthy Arteries

Niacin Augments the
Benefits of Statins

It boosts “good cholesterol” levels—
an invaluable function that might even help policosanol
By Will Block

hen affordable electronic calculators first hit the market, they created a sensation. What amazing ease of use and accuracy … and speed! Why, you could whip through lengthy computations in a flash, confident of nailing the correct answer without even thinking. You no longer had to remember what 9 times 7 was, or to carry the 4. Slide rules—those beautiful, sophisticated tools that were emblematic of scientists and engineers everywhere—bit the dust as cheap, powerful calculators took the world by storm.

Well, much of the world, anyway. Not everyone was bowled over by calculators—especially in China. In a speed-calculation contest held some years ago, one group of contestants with calculators was pitted against another group whose instrument was … the abacus. Guess who won? Yup, for speed with accuracy, the abacus cleaned the calculator’s clock, so to speak. So much for new-fangled devices.

Granted, calculators can do many things that the abacus cannot, but then, the abacus never needs a battery. As a basic, reliable, calculation workhorse, it can’t be beat (at least in China, where they know how to use them). The moral is that it’s not wise to let a trusty old friend get displaced too easily by something new and shiny, because you might be losing something valuable.

Statins 1, Niacin 0 (Temporarily)

Something like that could be said of niacin, a vitamin that was once the workhorse of cholesterol lowering—until those shiny new statin drugs were introduced in 1986 and dazzled the medical world with their capabilities. The statins are so effective and versatile (and so profitable for the drug companies!) that niacin was trampled in the statin stampede. It was all but forgotten as a cholesterol-lowering agent (but it’s still vital as a vitamin, naturally) except by adherents of alternative medicine and nutritional supplements.

The statin juggernaut is still growing—and not without reason. The past few years have seen an upsurge of belief by physicians that statins should be used much more aggressively, by many more people, than was previously thought necessary or prudent.* Reducing cholesterol levels in order to help prevent not just cardiovascular disease and diabetes, but also dementia, is becoming an ever-higher priority in medical practice. There have, however, been some problems with a few of the statins, such as side effects that caused one of them (cerivastatin) to be withdrawn from the market in 2001 and another one (rosuvastatin) to become controversial in November 2004, when an FDA official suggested that it too be withdrawn.


*For discussions of some of the studies supporting this belief, see “Our Cholesterol Levels Are Still Too High” (October 2003), “Got Cholesterol? Lower It!” (May 2004), “A Sea Change in Cholesterol Thinking” (June 2004), and “You Can—and Ought to—Lower Your Cholesterol” (October 2004).


Problem in Statinland: They’re Weak on HDL

But there is another, more fundamental problem with the statins: for all their vaunted ability to reduce total cholesterol and LDL (low-density lipoprotein, also called “bad cholesterol”), they are not particularly effective in raising the levels of HDL (high-density lipoprotein, also called “good cholesterol”). Until the last few years, this was not cause for much concern, because the primary focus was on LDL as a cardiovascular risk factor. Recent research, however, has suggested that aggressively raising our levels of HDL (which acts as a vehicle for removing excess cholesterol from the circulation) may be much more valuable in reducing our risk than was previously thought, because HDL has emerged as an important independent risk factor for cardiovascular disease.1

Put another way, the risk associated with having low HDL levels, even if our total cholesterol and LDL levels are also low, appears to be much greater than had been thought. In people with this condition, the atherosclerosis that underlies much cardiovascular disease is likely to progress despite their low LDL levels—bad news for the heart!

Thus the real objective is to minimize the ratio of LDL to HDL, by both lowering the former and raising the latter as much as possible. It is desirable for this ratio to be no greater than 3.5, and preferably much less.

Niacin—The Big Comeback

Enter niacin, which is known to reduce cardiac morbidity and mortality when taken either alone or in combination with statins. Importantly, it has the HDL-raising ability that statins can only wish they had—niacin is the most effective therapy available for the treatment of low HDL levels.2,3 Epidemiological studies suggest that an increase of 1 mg/dL in HDL is associated with a roughly 2–4% reduction in coronary heart disease outcomes.4 Suddenly the long-forgotten niacin is looking pretty good again.

A paper presented in November 2004 at the American Heart Association’s annual meeting in New Orleans, and published in the journal Circulation, described the results of a 1-year study at the Walter Reed Army Medical Center in Washington, DC, using “prescription-strength” niacin (1000 mg/day) in 149 men and women (average age 67).5 All of them had coronary heart disease, moderately low LDL levels (average 89 mg/dL), and moderately low HDL levels (average 40 mg/dL), and all of them were taking statin drugs.


Importantly, niacin has the HDL-
raising ability that statins can only
wish they had—it is the most
effective therapy available for the
treatment of low HDL levels.


The niacin was of the extended-release type, which tends to reduce, but not eliminate, the notorious but harmless “flushing” effect caused by this compound in doses of more than about 100 mg/day. This flushing of the skin, which gradually subsides as the body becomes accustomed to the niacin, is due to vasodilation (expansion of the blood vessels). A surprising number of people find it pleasant—if not initially, then eventually.

Niacin Boosts HDL, Reduces Cardiac Risk

The niacin/statin study was the first clinical trial using the two-pronged approach to cholesterol levels described above. It was randomized, double-blind, and placebo-controlled, so the effects observed could be attributed to niacin alone. And these effects were:

  • HDL levels increased by an average of 8 mg/dL (21%) with niacin; they were unchanged with placebo.
  • Triglycerides (fats) decreased by 13% with niacin; with placebo they decreased by 4.7%.
  • Carotid-artery inner wall thickness (a measure of plaque buildup and hence of cardiovascular risk) remained unchanged with niacin; it increased slightly but significantly with placebo, indicating further progression of the disease. (An ultrasound technique was used for these measurements.)
  • Clinical cardiovascular events occurred in 3 patients on niacin (3.8%); they occurred in 7 patients on placebo (9.6%).
  • No patient experienced significant liver-function problems (which is a possibility with high-dose niacin) or other serious side effects. Skin flushing occurred in 69% of the patients on niacin and in 13% of those on placebo.

Thus, this study suggests the added value of niacin therapy for increasing HDL levels in patients with heart disease, even when they’re taking statin drugs. The authors expressed reservations, however, about the study’s relatively small size, and recommended further work to confirm these results.

Policosanol and Niacin—Dynamic Duo

If niacin can augment the benefits of statin drugs, it seems reasonable to suppose that it could do the same for the nutritional supplement policosanol, whose impressive spectrum of cholesterol-lowering benefits has been the subject of many articles in this magazine.* Included in that spectrum, ironically, is a significant HDL-raising effect that consistently outshines the more limited effect of the statins. In 13 randomized, double-blind, placebo-controlled studies conducted on patients with high cholesterol levels, policosanol—predominantly in the dosage range of 5 to 20 mg/day—not only dramatically lowered LDL levels but also raised HDL levels by up to 29% (these increases were statistically significant in 7 of the 13 studies).6


*Some recent articles on policosanol’s role in heart health include: “Policosanol—Nature’s Remedy for High Cholesterol” (February 2002), “Policosanol—A Better Alternative to Statin Drugs” (May 2002), “Policosanol Improves Every Measure of Blood Cholesterol” (October 2002), “Policosanol Keeps Your Arteries Healthy” (November 2002), and “Policosanol Improves Cardiovascular Health” (December 2002).


Thus, it would seem at first that niacin doesn’t have as much to add to policosanol as it does to the statins. But considering how important it is to increase HDL levels as much as possible, it still makes sense to combine niacin with policosanol, because every bit of increase helps.

Stay Sharp!

Raising our HDL levels is good not only for our cardiovascular health but also for our cognitive health. It’s probably no coincidence that high HDL levels correlate with sharp cognitive function in centenarians, because HDL protects the cerebral arteries as well as the coronary arteries (and all the rest).7

And HDL may be good for longevity in general. It’s also probably no coincidence that most centenarians (and their children) have unusually high HDL levels.8 One study, in fact, found that the HDL levels in centenarians were similar to those of a control population about 30 years younger.9 (The important relationship between HDL and longevity was discussed in “One Hundred Reasons for Taking Policosanol” in the January 2003 issue.)

So if you wish to do your heart, your brain, and the rest of yourself a long-lasting favor, give your HDL levels as big a boost as you can, by eating a healthy diet, getting plenty of exercise (a great HDL booster), and reacquainting yourself with a trusty old workhorse, niacin, and its newer friend, policosanol.

References

  1. Assmann G, Gotto AM. HDL cholesterol and protective factors in atherosclerosis. Circulation 2004;109(Suppl III):III–8-14.
  2. Capuzzi DM, Guyton JR, Morgan JM, Goldberg AC, Kreisberg RA, Brusco OA, Brody J. Efficacy and safety of an extended-release niacin (Niaspan): a long-term study. Am J Cardiol 1998;82:74U-81U.
  3. Guyton JR, Goldberg AC, Kreisberg RA, Sprecher DL, Superko HR, O’Connor CM. Effectiveness of once-nightly dosing of extended-release niacin alone and in combination for hypercholesterolemia. Am J Cardiol 1998;82:737-43.
  4. Gordon DJ, Probstfield JL, Garrison RJ, Neaton JD, Castelli WP, Knoke JD, Jacobs DR Jr, Bangdiwala S, Tyroler HA. High-density lipoprotein cholesterol and cardiovascular disease: four prospective American studies. Circulation 1989;79:8-15.
  5. Taylor AJ, Sullenberger LE, Lee HJ, Lee JK, Grace KA. Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2: a double-blind, placebo-controlled study of extended-release niacin on atherosclerosis progression in secondary prevention patients treated with statins. Circulation 2004;110. (In press)
  6. Janikula M. Policosanol: a new treatment for cardiovascular disease? Alt Med Rev 2002;7(3):203-17.
  7. Atzmon G, Gabriely I, Greiner W, Davidson D, Schechter C, Barzilai N. Plasma HDL levels highly correlate with cognitive function in exceptional longevity. J Gerontol Med Sci 2002;57A(11):M712-5.
  8. Barzilai N, Gabriely I, Gabriely M, Jankowitz N, Sorkin JD. Offspring of centenarians have a favorable lipid profile. J Am Geriatr Soc 2001;49:76-9.
  9. Wilson PWF, Keaven M, Anderson M, Harris T, Kannel WB, Castelli WP. Determinants of change in total cholesterol and HDL-C with age: the Framingham study. J Gerontol Med Sci 1994;49:M252-7.

A Niacin Primer


Niacin is found in many plant and animal foods. The richest sources of this vitamin are white meats, most organ meats, certain fishes, peanuts, and yeast; many other foods contain niacin in lesser amounts. Niacin is water-soluble and is one of the most stable vitamins, resisting most cooking and preserving processes. For commercial purposes, it is prepared mainly by chemical synthesis from quinoline, a compound obtained from coal tar.

Like thiamine (vitamin B1) and riboflavin (vitamin B2), niacin (vitamin B3) is a coenzyme involved in carbohydrate metabolism and many other physiological processes. In large therapeutic doses, it serves as a potent cholesterol-lowering agent—the most cost-effective one known. Niacin is extremely safe to use. It has been used for many years in the treatment of mental diseases, especially schizophrenia, at daily doses of up to 50 g; the average dose prescribed by orthomolecular psychiatrists is about 8 g/day (with the same amount of vitamin C and, usually, a variety of other nutrients as well).1

Niacin is the common name for the simple organic compound known to chemists as nicotinic acid (because it’s obtained by the oxidation of nicotine). A chemical derivative of niacin that is metabolically equivalent to the vitamin (i.e., it has essentially the same vitamin activity) is niacinamide, which is also called nicotinamide. This compound is a precursor to nicotinamide adenine dinucleotide (NAD), a molecule of great biological importance because of the vital role it plays in many metabolic processes, including cellular respiration. NAD also serves as a key player in a process, gene silencing, that is involved in the regulation of longevity in a broad variety of species.

In nutritional supplements, niacin is often provided as the related (and similarly biologically active) compounds niacinamide ascorbate or inositol hexanicotinate, which are non-flushing forms of the vitamin.

  1. Pauling L. How to Live Longer and Feel Better. W. H. Freeman, San Francisco, 1986, pp 24, 260-1.

How Sick Crooks and Dogs Helped Science


Joseph Goldberger
Before anyone knew what niacin was, the Austrian-American physician Joseph Goldberger devoted much effort to solving the riddle of pellagra, a serious disease that was endemic in impoverished parts of the American South, among other regions. Pellagra is characterized by 4 D’s: dermatitis, diarrhea, dementia, and death. No one knew what caused it, but Goldberger came to suspect that it occurred when the diet was seriously deficient in meat, milk, and eggs.

In 1915, after a 10-year-long outbreak of pellagra in the South, he conducted a dramatic experiment on prisoners in a Mississippi jail. With the state’s promise of pardons in return for their cooperation, the prisoners were put on a diet lacking any meat, milk, or eggs. Within 6 months, they developed pellagra, which Goldberger and his assistants tried hard to contract through close contact with the prisoners, their clothing, and even their excretions (talk about dedication!). The researchers failed, proving that pellagra was not infectious.

Goldberger then cured the prisoners by adding meat, milk, and eggs to their diet, proving that pellagra was caused by a deficiency of something that those foods contained. It was not until 1937, however, that that something was shown, by the American biochemist Conrad Elvehjem, to be nicotinic acid, or niacin. He did this in an experiment with dogs that had blacktongue, the canine version of pellagra. Thus, niacin was recognized to be a vitamin.

Ironically, it turned out that, although certain meats are indeed rich sources of niacin, the same is not true of milk and eggs, which are very poor sources of the vitamin. Yet milk and eggs alone can cure pellagra—how can that be? The answer was discovered in 1947: milk and eggs are rich in proteins that are rich in the amino acid tryptophan, and our bodies convert a small amount of that tryptophan (with the help of vitamin B6) to niacin. Thus, our main source of dietary niacin is actually the tryptophan in our food.

Caution: Anyone who wishes to take more than 600 mg/day of supplemental niacin (from all sources combined, including multivitamins) should seek the advice of a healthcare professional. Liver-function tests should be done initially, and periodically thereafter, to ensure that the liver is not overburdened.


Will Block is the publisher and editorial director of Life Enhancement magazine.

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