(fwd) Re: niacin toxicity

Doug Skrecky (oberon@vcn.bc.ca)
Sun, 29 Nov 1998 21:32:11 -0800 (PST)

From: crowley9@ix.netcom.com
Newsgroups: misc.health.alternative,sci.med.nutrition

> Doug Skrecky wrote:
> >
> > In (JAMA 271: 672-677 1994) sustained release niacin was found to
> > induce hepatoxic effects in 52% of patients, while none of those given
> > immediate release niacin developed these side effects. The effects on
> > lipids with these two formulations was quite different as well - as
> > follows:
> >
> > Dosage Formulation HDL LDL LDL/HDL Triglycerides
> > 0.5 gm/day immediate +8.6% -1.9% -9.7% -11.2%
> > 1 immediate +25.3 -6.3 -25.2 -28.9
> > 1.5 immediate +29.8 -13.7 -33.5 -30.2
> > 2 immediate +31.1 -16.1 -36.0 -39.0
> > 3 immediate +35.0 -21.7 -42.0 -41.8
> >
> > 0.5 sustained -1.8 -5.8 -4.0 -6.6
> > 1 sustained +2.3 -11.9 -13.9 -6.7
> > 1.5 sustained +12.5 -21.9 -30.6 -25.2
> > 2 sustained +17.2 -32.5 -42.4 -30.2
> > 3 sustained +9.4 -50.0 -54.2 -41.1
> >
> > At low 1 gm/day doses of niacin the immediate release form is
> > dramatically more effective, as well as being safer than sustained
> > release niacin. IMHO, sustained release niacin should be withdrawn from
> > the OTC market.
> But at 1.5 or 2 grams per day (when both began to have a major effect)
> even this study shows it's a toss-up. In addition, more recent studies
> which I have posted several times on other threads, show that at
> practical doses, time-release and other non-flush niacin are almost as
> benefical for cholesterol, not more liver toxic, and induce more patient
> compliance than regular niacin.
> However, the lastest investigations suggest the possibility that
> cholesterol changes may only happen *because* of induced liver toxicity.
> In that case, no form of niacin should be used as a cholesterol
> reduction therapy. Since there are other effective dietary (non-drug)
> interventions, that is my current recommendation.
> --Tom

In the book, The Encyclopedia of Nutritional Supplements (1996, Prima Publishing) by Michael Murray, N.D. (a book I strongly recommend for its thoroughness and many references), here's some of what he says for niacin.

Beneficial Effects

Niacin supplementation exerts a favorable effect on several health conditions, especially high cholesterol levels.

Available Forms

Vitamin B3 is available in nutritional supplements as either niacin (nicotinic acid or nicotinate) or niacinamide (nicotinamide). Each form has different applications. In its nicotinic form, vitamin B3 is an effective reducer of blood cholesterol levels. While in its niacinamide form, it is useful in arthritis and early-onset type I diabetes.

Doses in excess of 50 mg of niacin, but not niacinamide, typically produce a transient flushing of the skin. To get around the problem of skin flushing, drug and supplement manufacturers have developed "timed-released" products. However, while these preparations may effectively eliminate the problem of skin flushing, they are associated with greater liver destruction and serious side effects (discussed below under Safety Issues). A better way to eliminate the problem of skin flushing is to use inositol hexaniacinate (also known as inositol hexanicotinate and, for short, hexaniacin). This form of niacin has been used in Europe for over 30 years with an excellent safey record.

Principal Uses

The principal uses of niacin and inositol hexaniacinate are in the treatment of elevated cholesterol and triglyceride levels, Raynaud's phenomenon, and intermittant claudication. Niacinamide is used in recent-onset type I diabetes mellitus and arthritis.

Comparative Studies

The lipid-lowering activity of niacin was first described in the 1950s. We now know niacin does much more than lower total cholesterol. Specifically, niacin lowers LDL cholesterol, Lp(a) lipoprotein, triglyceride, and fibrinogen levels, while simultaneously raising HDL cholesterol levels (ref 1).

The famed Coronary Drug Project demonstrated that niacin was the only lipid-lowering agent to actually reduce overall mortalilty (ref 2). Its effects are long-lasting as demonstrated in a 15 year follow-up study to the Coronary Drug Project.

Inositol Hexaniacinate

Inositol hexaniacinate is a special form of niacin composed of six nicotinic acid molecules bound to and surrounding one molecule of inositol, an unofficial member of the B vitamin group. Inositol hexaniacinate exerts the benefits of niacin without flushing or other side effects. It has been used in Europe for over 30 years not only to lower cholesterol, but also to improve blood flow in the treatment of claudication. Although inositol hexaniacinate yelds slightly better results than standard niacin, the big advantage is that it is safer and much better tolerated (ref 12 & 13).

Dosage Ranges

You should not use sustained-release niacin. If you use pure crystalline niacin, start with a dose of 100 mg three times a day and carefully increase the dosage over a period of 4 to 6 weeks to the full therapeutic dose of 1.5 grams to 3 grams daily in divided dosage. If you are using inositol hexaniacinate, begin with 500 mg 3 times daily for 2 weeks and then increase to 1000 mg. It is best to take either crystalline niacin or inositol hexaniacinate with meals.

Safety Issues

The side effects of niacin are well known. The most common and bothersome side effect is the skin flushing that typically occurs 20 to 30 minutes after taking the niacin. Other occasional side effects of niacin include gastric irritation, nausea, and liver damage. In an attempt to combat the acute reaction of skin flushing, several manufacturers began marketing "sustained-release","timed-released", or "slow-released" niacin products. Although these forms of niacin reduce skin flushing, they are actually more toxic to the liver. A recent study published in the Journal of the American Medical Association (JAMA) strongly recommended that sustained-released niacin be restricted from use because of the high percentage (78 percent) of patient withdrawal because of side effects; 52 percent of the patients taking the sustained-release niacin developed liver damage, while none of the patients taking immediate-release niacin developed liver damage (ref 42).

Again, inositol hexaniacinate is the safest form of niacin currently available. Both short- and long-term studies show it is virtually free of side effects other than an occasional person experiencing mild gastric upset or mild skin irritation.

Because niacin can impair glucose tolerance, it should probably not be used in diabetics unless they are under close observation. Niacin should not be used in patients with pre-existing liver disease or elevation in liver enzymes, gout, or peptic ulcers.

Regardless of the form on niacin being used, periodic checking (minimum every 3 months ) of cholesterol and liver function tests are indicated when high-dose (i.e., 2 to 6 grams per day) niacin, inositol hexaniacinate, or niacinamide therapy is being used.

ref 1
DiPalma JR and Thayer WS, Use of niacin as a drug. Annu Rev Nutr, 11, 169-187, 1991.

ref 2
The Coronary Drug Project Group, Clofibrate and niacin in coronary heart disease. JAMA, 231, 360-381, 1975.

ref 12
Welsh AL and Ede M, inositol hexanicotinate for improved nicotinic acid therapy. Int Record Med, 174, 9-15, 1961.

ref 13
El-Enein AMA, et al., The role of nicotinic acid and inositol hexaniacinate as anticholesterolemic and antilipemic agents. Nutr Rep Intl, 28, 899-911, 1983.

ref 42
McKenney JM, et al., A comparison of the efficacy and toxic effects of sustained- vs. immediate-release niacin in hypercholesterolemic patients. JAMA, 271, 672-677, 1994.