Lower Cholesterol Without The "Flush"

Nicotinic acid, which is better known as niacin or vitamin B3, is so good at normalizing blood lipid levels that it has been declared the treatment of choice for reducing cholesterol by none other than the Expert Panel of the National Cholesterol Education Program (NCEP).1

This is about as close as you get to an official policy in American medicine, and it's quite an endorsement, considering the many expensive prescription cholesterol-lowering drugs on the market.

The NCEP's conclusion was based on many scientific studies showing that high doses of nicotinic acid (1.5-2 gm/day) have a triple action matched by no other anticholesterol drug: it raises levels of HDL (the "good" cholesterol) while lowering levels of LDL (the "bad" cholesterol) and triglycerides (also "bad"). In fact, nicotinic acid may be the best agent currently available for raising HDL.2 High doses have been shown to increase HDL by 30% or more,3,4 which can make a significant improvement in your cardiovascular health.

"If you're concerned about your cholesterol levels, but you can't tolerate the niacin flush, your next step should be inositol hexanicotinate (IHN)"

As good as it is, though, nicotinic acid has certain drawbacks including headaches, reduced glucose tolerance, and elevated liver enzymes. The most common, however, is the "niacin flush" in which your skin gets warm, and red, and itchy for a few minutes after you take your dose. The flush is caused by a transient dilation of peripheral blood vessels due to a large release of histamine. It is annoying and uncomfortable but harmless, and if you continue to take nicotinic acid, you soon adapt to it and rarely experience it again even at high doses. But many people find the flush so unpleasant that they stop taking niacin, or they take doses that are too low to be effective.

If you can't tolerate nicotinic acid, you're in luck. A chemical cousin of nicotinic acid called inositol hexanicotinate (IHN) may be at least as effective in normalizing blood lipid levels, and it doesn't cause a flush. Although many people are just now becoming aware of IHN as a means of controlling cholesterol, it has actually been around for a long time in Europe for treating diseases of the peripheral circulation like intermittent claudication and Raynaud's syndrome.5-9

What is IHN?

First, don't confuse IHN with "timed-released" or "sustained-release" niacin. These formulations are simply niacin packaged to dissolve more slowly and hence, be released more slowly into the blood stream. Although sustained-release niacin formulations usually do what they promise, they have been associated with an increased risk of liver toxicity,10 elevated liver fatty acids, and even liver transplants! Chemically, a molecule of IHN is simply six molecules of niacin attached to a single molecule of inositol.11

When it enters the body, IHN is broken down into its component parts, releasing niacin into the blood stream. Here it is free to perform its well-known anticholesterolemic act, which includes inhibited lipolysis, improved peripheral glucose utilization, and reduced levels of glycolysis products in serum.12 The addition of inositol, however, seems to slow the metabolism of the nicotinate molecules. This has two important beneficial effects:11

  • It prevents the flush that typically occurs with the rapid introduction of high doses of niacin, and
  • It extends the anticholesterolemic effect of the niacin over a longer period of time. In one study, it took 10 hours before the maximum effect of an intravenous dose was reached.

Four Decades of Research

Studies showing that IHN improves lipid profiles date back as far as the early 1960s.11,13,14 In an in vitro study using fat cells from rats, IHN was found to be more effective than niacin in reducing hypercholesterolemia.15 When given to rabbits on a fatty diet, IHN resulted in normalization of all lipid fractions, including cholesterol.16

In human subjects, IHN has been shown by two research groups to produce a reduction in cholesterol that was even more profound than that produced by niacin.11,16 In a clinical study conducted in Germany, IHN was compared with niacin and other nicotinic acid derivatives for their ability to control free fatty acid levels overnight. IHN, but not niacin, was found to be capable of producing a significant reduction in free fatty acids during the entire night. The authors suggested that IHN should be a good choice for producing a prolonged reduction in blood lipids.17

Two other German studies examined the treatment of various types of hyperlipidemias using a drug combination composed of IHN and another anticholesterol drug, clofibrate. The investigators found this drug to be quite effective in reducing levels of LDL and VLDL (very low density lipoprotein)-triglycerides, and was also effective in raising HDL levels in some types of hyperlipidemia. They emphasized that the drug was well-tolerated.18,19

"The experience that has been gained in these studies in treating peripheral circulatory disorders and dyslipidemias suggests that it is a safe and effective alternative to niacin and does not cause the flush that many people find so unpleasant"

Since virtually all the work on IHN has been carried out and published in Europe, it is not well-known in the United States. Nevertheless, the experience that has been gained in these studies in treating peripheral circulatory disorders and dyslipidemias suggests that it is a safe and effective alternative to niacin and does not cause the flush that many people find so unpleasant. So, if you're concerned about your cholesterol levels, but you can't tolerate the niacin flush, your next step should be IHN.

References

1. The Expert Panel. Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection. JAMA. 1993;269:3015-3023.
2. Martin-Jadraque R, Tato F, Mostaza JM. Effectiveness of low-dose crystalline nicotinic acid in men with low high-density lipoprotein cholesterol levels. Arch Int Med. 1996;156:1081-1088.
3. Alderman JD, Pasternak RC, Sacks FM, Smith HS, Monrad ES, Grossman W. Effect of a modified, well-tolerated niacin regimen on serum total cholesterol, high density lipoprotein cholesterol and the cholesterol to high density lipoprotein ratio. Am J Cardiol. 1989;64:725-730.
4. Vega GL, Grundy SM. Lipoprotein responses to treatment with lovastatin, gemfibrozil, and nicotinic acid in normolipidemic patients with hypoalphlipoproteinemia. Arch Int Med. 1994;154:73-82.
5. Ring EFJ, Porto LO, Bacon PA. Quantitative thermal imaging to assess inositol nicotinate treatment for Raynaud's syndrome. J Int Med Res. 1981;9:393-400.
6. O'Hara J, Jolly PN, Nicol CG. The therapeutic efficacy of inositol hexanicotinate (Hexopal®) in intermittent claudication: A controlled trial. Br J Clin Pract. 1988;42:377-383.
7. Murphy R. The effect of inositol hexanicotinate (Hexopal) in patients with Raynaud's syndrome. Clin Trials J. 1985;22:521-529.
8. Kiff RS. Does inositol hexanicotinate (Hexopal) influence intermittent claudication? Br J Clin Pract. 1988;42:141-145.
9. Head A. Treatment of intermittent claudication with inositol nicotinate. Practitioner. 1986;230:49-54.
10. McKenney JM, Proctor JD, Harris S, Chinchili VM. A comparison of the efficacy and toxic effects of sustain- vs immediate-release niacin in hypercholesterolemic patients. JAMA. 1994;271:672-677.
11. Welsh AL, Ede M. Inositol hexanicotinate for improve nicotinic acid therapy. Int Record Med. 1961;174:9-15.
12. Hammerl H, Kraenzyl CH, Sudlar M. Metabolic studies for determination of the action mechanism of a ß-sympathometic. Wein Klin Woschenschr. 1968;80:269.
13. Sommer H. Nicotinic acid levels in the blood and fibrinolysis under the influence of the hexanicotinic ester of m-inositol. Arzneim Forsch. 1975;15:1337.
14. Dorner VG, Fischer FW. The influence of m-inositol hexanicotinate ester on the serum lipids and lipoproteins. Arzneim Forsch. 1961;11:110-113.
15. El-Eneim AMA, Hafez YS, Salem H, Abdel M. The role of nicotinic acid and inositol hexanicotinate as anticholesterolemic and antilipemic agents. Nutr Reports Int. 1983;28:899-911.
16. Mercier J, Gavend MR, Dessaigne S. Effect of inositol and its derivatives on hypercholesterolemic rabbits. Cong Union Therap Intern (Brussels). 1963;8:11.
17. Kruse W, Kruse W, Raetzer H, et al. Nocturnal inhibition of lipolysis in man by nicotinic acid and derivatives. Eur J Clin Pharmacol. 1979;16:11-15.
18. Hutt V, Wechsler JG, Klor HU, Ditschuneit H. On the effect of a combination of clofibrate and inositol hexanicotinate on lipids and lipoproteins in primary hyperlipoproteinemia types IIa, IV, and V. Arzneim Forsch. 1983;33:776-779.
19. Wechsler JG, Hutt V, Kloer H-U, Ditschuneit H. Lipids and lipoproteins in hyperlipidemia type IIa during treatment with different lipid lowering drugs. Artery. 1980;8:519-529.

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