Niacin: Ins and outs, ups and downs
TRACK YOUR PLAQUE SITE
Niacin—vitamin B3—corrects multiple lipoprotein patterns. Used properly, niacin is a safe, effective treatment that results in dramatic reduction in heart disease risk. Used improperly, it can be full of unwanted adverse effects, most annoying, some dangerous. Here's a roadmap to negotiate the ins and outs, ups and downs of niacin.
Have you ever taken a B-complex vitamin pill that triggered a strange burning skin sensation?
Well, if you have, that's the niacin in the pill.
Niacin is vitamin B3, sometimes also called "nicotinic acid". It's found naturally in red meats, chicken, turkey, beans, and grains. Niacin is a required nutrient and member of the larger B-vitamin family ("B-complex"). Niacin plays a role in crucial body processes including generation of energy, gene expression, and hormone synthesis. Humans cannot exist without niacin. The disease pellagra, seen on a widespread scale in the U.S. during the 19th century, is now long-forgotten and rarely seen.
The Recommended Daily Allowance (RDA) of niacin to prevent pellagra is 16 mg per day for males, 14 mg per day for females. However, an array of health benefits develop when niacin is taken at doses greater than the RDA.
Niacin—Answer to many lipoprotein disorders
Niacin is capable of an amazing array of lipoprotein benefits. For this reason, around 70% of all Track Your Plaque participants take niacin.
Niacin's effects include:
* Increased HDL
* Decreased small LDL
* Decreased triglycerides
* Decreased VLDL
* Decreased lipoprotein(a)
* Decreased LDL
Niacin yields these wonderful lipoprotein benefits by blocking release of fatty acids from fat cells. Less fatty acids are therefore presented to the liver, resulting in less VLDL particles. Less VLDL leads to less small LDL and higher HDL.
Niacin reduces heart attack risk dramatically. The Coronary Drug Project, a landmark study in heart disease prevention, was the first to establish niacin as a powerful agent to slash heart attack risk. 8,341 men who had suffered heart attack were given 3000 mg of niacin ("crystalline", or immediate-release) over six years. Total cholesterol levels were reduced by 10% and triglyceride levels by 26%. Treatment with niacin resulted in a decrease of 27% in heart attacks among the nicotinic-acid treated subjects. They also experienced 26% fewer strokes.
The ARBITER series of studies examined the effects of niacin on carotid plaque. Regression can be achieved using this measure when niacin is added to statin therapy.
The HDL-Atherosclerosis Treatment Study (HATS) was another landmark study demonstrating niacin's huge benefits. In HATS, 160 participants (149 males), all of whom had documented coronary disease, were given combinations of simvastatin (Zocor®) and niacin or placebo. When the group receiving simvastatin and niacin were compared to the placebo group, there was a 90% reduction in death and myocardial infarction (12 events placebo;1 event simvastatin + niacin) over three years. In other words, coronary events were nearly shut off. Small numbers but persuasive.
(To put this into perspective, recall that all the major clinical trials of lipid therapy, such as 4S, LIPID, AFCAPS/TEXCAPS, Heart Protection Study, etc. achieved event reductions of 25-35% over approximately 3 to 5 years when LDL cholesterol was lowered by statin drugs. The 90% achieved in the HATS Trial is therefore truly phenomenal.)
Rarely do we see a treatment effect as powerful as the reduction in events seen in the HATS Trial.
Who should consider taking niacin?
We believe that the HATS Trial and related evidence very powerfully confirm that raising HDL can lead to a profound reduction in coronary events.
From the Track Your Plaque viewpoint, in which plaque shrinkage and inactivation is our goal, we aim to raise HDL to 60 mg/dl or greater. Following this approach, we should be able to match or exceed the 90% reduction in events of the HATS experience. Niacin can be tremendously helpful to achieve these goals.
Niacin is effective for reducing small LDL. It's also our number one choice for reduction of lipoprotein(a). (In fact, much of niacin's benefit in people with Lp(a) may arise from its effect on increasing LDL size.)
Niacin—Attention to detail pays off
Niacin is very safe and effective when used properly. But when used improperly, it can pose unacceptable risks to your liver. Attention to detail is therefore very important.
Three different types of niacin formulations are available:
1. Immediate-release, or "crystalline", niacin
2. Slow-release niacin
3. Extended- or "intermediate-release", niacin
Immediate-release or crystalline niacin is available in health food stores. It's cheap and very effective. However, it's intolerable for about everybody who takes it. Because of the annoying "hot-flush" effect that niacin provokes (see below), people will take small doses (e.g., 250 mg) three or four times per day to spread out the dose. This is unsafe. We do not recommend the use of this niacin form. If you do choose to use immediate-release niacin, never take it more than twice a day. Liver toxicity from niacin seems to develop when the liver is exposed to continuous blood levels of niacin as might occur when you take it three or four times a day.
Slow-release niacin gets around the hot flush effect fairly well through tablet formulations that trickle niacin out over an extended period of 12 or more hours. Most preparations are unsafe and we do not recommend them. These are the forms sold in health food stores as slow-release niacin. They are associated with an unacceptable risk for liver damage—up to 20% of people in some studies have had marked increases in liver tests that signal damage.
Slo-Niacin® (Upsher Smith Pharmaceuticals) is the one exception. Slo-Niacin® has the advantage of published data proving efficacy and safety; it was the form used in the HATS Trial (above). It is available over-the-counter in pharmacies. We recommend Slo-Niacin® given their track record. We've also used it extensively and not encountered any unusual problems.
Extended- or intermediate-release niacin is in between the above two—a little slower niacin release than immediate-release but not as slow as slow-release. It also provokes less hot flush than immediate-release. Niaspan® (Kos Pharmaceuticals) is the only formulation in this category and is the only FDA-approved niacin preparation, having survived the rigors of their assessment. It is available only by prescription.
We begin with 500 mg of Niaspan® or Slo-Niacin® at bedtime and increase by 500 mg every four weeks until the desired effect is obtained (e.g., rise in HDL, elimination of small LDL, reduction of Lp(a), etc.) A total dose of 1000–2000 mg is usually sufficient, though doses vary from person to person depending on body weight and genetic factors. Occasionally, as little as 750 mg niacin per day yields substantial effects. You and your doctor should keep in mind that full lipoprotein benefits of niacin often require a year or more to fully develop. Sometimes patience is required.
Niacin should be prescribed by a doctor who has experience in dealing with the peculiar effects of niacin like the hot flush, even if an over-the-counter form like Slo-Niacin® is chosen. Unfortunately, many patients and physicians are scared by these effects and give up. A knowledgeable professional is really crucial.
People with liver disease, unexplained elevations of liver tests, active peptic ulcer disease and a history of abnormal bleeding should discuss use of niacin with their physician before beginning any treatment with niacin.
Those with a past history of liver disease, jaundice, peptic ulcer disease or gastritis should exercise caution in the use of niacin. Gout may flare when niacin is used; discuss with your doctor if you have a history of gout.
Those who take 1000 mg or more of niacin per day should have their liver blood tests monitored. Aspartate aminotransferase (AST, also known as SGOT) and alanine aminotransferase (ALT, also known as SGPT) levels should be measured prior to beginning, then every 12 weeks for one year and after one year, periodically. High-dose nicotinic acid should be discontinued if the AST/ALT levels are equal to greater than three times the upper limit of normal.
Niacin may raise blood sugar a few points, particularly in individual with diabetes and pre-diabetes. Diabetics should have their serum glucose levels carefully monitored and the dose of their diabetic medications adjusted as necessary; work with your doctor.
HMG-CoA reductase inhibitors or "statins" (atorvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin, simvastatin) are often prescribed in combination with niacin. Initially, there were concerns that combination therapy would carry increased liver toxicity. However, this appears not to be the case. However, your doctor should monitor liver function on the combined therapy, just as he/she would on either agent alone.
Don't get burned by the "hot flush"!
The one common though generally harmless hurdle with niacin use is the dreaded "hot flush". It's bothersome enough that some people to want to flush niacin down the toilet!
The flush feels a lot like blushing when you're really embarrassed, except it's accompanied by a prickly sensation over the face, neck, and chest. Some women say it's a lot like hot flashes of menopause. It's usually transient, lasting no more than 20 minutes. Tolerance to this effect occurs with continued administration, usually after a few weeks or months. You may experience flushing both at the start of your niacin program, or with increases in dose. A rare person has a more marked flush reaction that looks like a rash or hives; if this occurs discuss continued use of niacin with your doctor. (We've found that low doses of niacin, e.g., 100–250 mg, for a prolonged period may be necessary to generate tolerance before dose escalation can occur.)
There are several practical strategies to follow that really help minimize or even eliminate the hot flush. These include:
* Take niacin at bedtime with an aspirin. When you start niacin and whenever your dose is increased, an adult (325 mg), uncoated aspirin is most effective to block the flush. After a few weeks or months, when the flushing dissipates, changing to a baby (81), enteric-coated aspirin can minimize stomach upset and the long-term risk of stomach ulcers and bleeding. (Of course, always discuss aspirin use with your doctor.)
* Take niacin with a handful (5–10) of raw almonds, walnuts, or pecans. This slows absorption. You might skip this if you're in the midst of a weight loss effort (i.e., avoid eating at bedtime).
* Drink plenty of water. This is very important and especially helpful if you experience a hot flush: drink two 8 oz. glasses of water immediately and the hot flush is almost always gone within a few minutes. (Discuss water intake with your doctor if you're on a fluid restriction because of kidney disease, heart disease, or a history of water retention, or if you take a diuretic.) If you find that you need to drink water to block hot flushes but you need to get up several times per night to urinate, you might do better to take your niacin in the morning with breakfast—but you must eat breakfast.
* Avoid alcohol and spicy foods when you take your niacin. This is not all that important, however. Only some people will be sensitive to this phenomena. It's okay to have a glass of wine, say, at 7 pm and then take your niacin at 9 pm. Only a rare person will have more flushing due to the combination.
Until something better comes along (torcetrapib?), niacin will remain a mainstay of most people's plaque-control program. Navigating the quirks of this helpful vitamin can really stack the odds in your favor while minimizing annoyances and side-effects.
What is not niacin
The crazy hot-flush effect that is responsible for many people's reluctance to stay on it has triggered the emergence of several alternatives to niacin. However, all of these alternatives are cheap impostors that have none of the benefits of real niacin. These include:
* Nicotinamide—It sounds like niacin. It may even look like niacin. But it's not. It has no beneficial effects in humans. This belongs in the placebo aisle.
* No-flush niacin—Or inositol hexaniacinate. No-flush, no-effect. Theoretically, this agent should work. It contains six niacin molecules attached to an inositol molecule. Rats do great on it, but humans lack the enzyme to break it down to effective niacin. It's also expensive—an expensive scam.
Should niacin be part of your program?
Niacin is a safe, effective choice for many, if not most, people interested in plaque-control and regression. The crucial hurdle for most people is identifying a physician who is comfortable with prescribing it and supervising its use. Unfortunately, many physicians simply don't want to be bothered. But you need to ask. If you get the "It's unsafe", "It's intolerable", etc., keep looking for a professional willing to take the time and effort. It's certainly worth it.
Selected References:
Canner PL, Berge KG, Wenger NK, et al. Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol. 1986; 8:1245-1255.
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 Dec 7;110(23):3512-7.
Simvastatin and Niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. B. Greg Brown, Zhao et al, N Engl J Med, 345:15831591, 2001.
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