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Getting the Niacin Story Right

Recently the media has once again failed to accurately report the significance of a clinical trial on a natural product. This time the subject was niacin. It’s important that health food retailers be prepared to answer questions that customers taking niacin may have in response to the recent media spotlight.

Why Customers Choose Niacin

There are several reasons why customers may choose to take niacin to lower cholesterol. First, their physician may prescribe it. Sales of the prescription form of niacin totaled nearly $1 billion in 2012. As the prescription form is about 10 times the price of over-the-counter (OTC) niacin, some customers may opt to buy niacin OTC.

Another reason is that some people cannot tolerate statin drugs due to the side effects. Fortunately, niacin can be as effective in lowering cholesterol levels as statins. Since the 1950s, niacin (vitamin B3) has been known to be effective in lowering blood cholesterol levels. In the 1970s, the famed Coronary Drug Project demonstrated that niacin was the only cholesterol-lowering agent to actually reduce overall mortality. Niacin typically lowers LDL (low-density lipoprotein) levels by 16-23 percent while raising HDL (high-level density lipoprotein) levels by 20-33 percent. While the effects on LDL compare quite favorably with conventional cholesterol-lowering drugs (i.e., statin drugs like Crestor, Lipitor, Zocor, etc.), niacin has the extra advantage of raising HDL—something the statin drugs do not impact. In addition, niacin has also been shown to lower the more harmful lipoprotein(a), triglycerides, and lower markers of inflammation such as CRP (C-reactive protein) and fibrinogen. Again, the statins do not affect these measures.

Niacin is also very useful in patients with the more damaging small and dense form of LDL particle. These denser forms carry with them an even greater significance in promoting atherosclerosis. The following chart shows a comparison of niacin to Lipitor from one of the previously mentioned studies:

Niacin Use With a Statin Drug

Because statins do not impact HDL levels, many physicians may recommend niacin to be taken with a statin. This approach can be quite helpful in people with high LDL and low HDL. However, niacin does not appear to enhance the benefits of statins in people whose LDL levels are below 100 mg/dl while on a statin. A recent study known as the AIM-HIGH study funded by the National Heart, Lung, and Blood Institute demonstrated no additional benefit with niacin use. The study ended 18 months early because no additional cardiovascular benefit was seen in those taking niacin.

An even more recent study is the one that has resulted in a lot of confusion on the benefits and risks of taking niacin. I am referring to the media’s reporting of the results from the HPS2-THRIVE study. This study involved more than 25,000 patients at high risk for a heart attack who were taking either the statin drug simvastatin alone or in combination with another drug ezetimibe (Vytorin). The average LDL in these patients was less than 65 mg/dl. So, once again the study was in people with very low LDL, so it is not clear why the researchers were expecting to see any benefit with niacin use.

The study subjects were randomized to take either a placebo or Tredaptive—(a drug produced by Merck containing niacin and an “anti-flushing agent” known as laropiprant). Niacin caused average reductions in LDL of 10 mg/dl and triglycerides of 33 mg/dl while increasing HDL by 6 mg/dl, but provided no additional benefit over the statin alone in reducing the rate of heart attacks or other vascular events.

Making matters worse, the Tredaptive group experienced a high rate of serious adverse events (i.e., every three out of 100 niacin-treated patients suffered from increased bleeding, infections, new onset diabetes, or other serious side effects). However, since these side effects had not been seen in other niacin plus statin trials, it is extremely likely the side effects were due to the anti-flushing agent laropiprant and not the niacin. Still, consistent with other combination trials, the use of niacin with a statin increased the likelihood of muscle damage caused by the statin.

Commentary

The media and conventional medical community are having a field day commenting on this study, which does not erase the considerable scientific base of niacin as a medicine at all. It only casts a blow in using niacin with an anti-flushing drug in patients taking statin drugs who have well-controlled LDL levels.

The media reported that niacin provided no benefits and caused serious side effects. My feelings are that the media is ignoring some important considerations. First, as mentioned previously, this trial made absolutely no sense as the average LDL in the group was 63 mg/dl well below the recommended level of less than 100 mg/dl for this patient population. Even in high-risk individuals it would be highly unlikely that further reduction of LDL by niacin would show any significant impact on reducing cardiovascular mortality.

While niacin is definitely effective on its own and offers a viable alternative to statins, I do agree with the HPS2-THRIVE finding that niacin should not be used in high-risk patients with low LDL levels.

What has yet to be determined is the effect of niacin combined with a statin in patients with poorly controlled LDL and low HDL. That is the type of study that needs to be performed. In addition, there needs to be a well-designed trial comparing niacin therapy to statins with the primary end point being the effect on overall mortality. I would put my money on niacin based upon the broader range of effects.

Practical Considerations

The side effects of niacin are well known. The most common and bothersome side effect is the skin flushing that typically occurs 20-30 minutes after taking it. Other occasional side effects of niacin include gastric irritation, nausea and liver damage. In an attempt to combat the acute reaction of skin flushing, slowrelease niacin products allow the niacin to be absorbed gradually, thereby reducing the flushing reaction.

It is important to point out that earlier timed-release preparations were proven to be more toxic to the liver than regular niacin. The newer timed-released preparations on the market, referred to as “intermediate-release,” appear to have solved this problem, as relatively large clinical trials have shown them to be extremely well-tolerated with the major side effect being occasional flushing. Intermediate-release formulations release the niacin steadily over a six- to eighthour period. They are now the preferred form for lowering blood lipids.

Inositol hexaniacinate is another form of niacin that does not cause flushing, but a recent double-blind study has now called into question its effectiveness.

Regardless of the form of niacin, it is important for anyone taking niacin at dosages greater than 500 mg daily to consult their physician to periodically check their cholesterol and liver function (initially every three months, yearly after that). Niacin should not be used in those with preexisting liver disease or elevation in liver enzymes. For these people, there are ample natural products with confirmed cholesterol-lowering effect that can be used (e.g., citrus polymethoxylated flavones [Sytrinol™], plant sterols, garlic, pantethine, etc.).

In general, it is recommended that niacin should be taken at night. Typically, niacin (1,000-2,000 mg at night) reduces total cholesterol by 50-75 mg/dl within the first two months. Once blood targets are reached, the dosage is usually personalized by the response by the customer’s physician usually based upon a target of less than 150 mg/dl for the LDL cholesterol.

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