Nutrition Tip of the Week--Counteracting the Niacin Flush

Monday, February 25

Niacin (vitamin B3) is perhaps the most effective nutritional supplement for lowering cholesterol. But unlike statins, not only does it lower cholesterol, it also significantly drops triglycerides while at the same time raising beneficial HDL cholesterol. Additionally, niacin may be one of the few ways to lower pesky lipoprotein (a), a little-known but significant heart disease risk factor. This suggests that it may be an ideal agent for reducing cardiovascular risk (along with fish oil and plant phytosterols).

As I so often reiterate, it's not nice to fool with Mother Nature. A prospective block-buster HDL-raising drug called torcetrapib crashed and burned last year when a trial showed the expensive new synthetic, unlike niacin, increased cardiovascular deaths instead of preventing them.

Drug companies, while providing niacin in prescription form (e.g. Niaspan) have had trouble bankrolling the supplement because cheap forms can be obtained over-the counter in health food stores. The financial incentives are therefore skewed toward costly statin drugs.

Stung by negative findings about the cholesterol-lowering drugs Zetia and Vitorin and new skepticism about statins, the pharmaceutical giants are seeking to recapture market share with new, "innovative" lipid formulations. The latest will be Abbott Labs' Simcor, simply a combo of old-fashioned Zocor and Niacin.

When combined with statins, niacin produces even greater reductions of cholesterol, and the latest trial of Simcor showed an additional reduction of 27% in triglycerides. But why it's easier to reach for a prescription combo drug when niacin is available in health food stores is beyond me. And besides, Abbott's "new" drug is simply a copy-cat of Kos Pharmaceuticals' Advicor combining Lipitor and niacin, available since 2001.

Problem: Acceptance of high-dose niacin is limited by its tendency to produce flushing in about 75% of patients. Typically, within minutes or hours of consuming niacin, subjects report skin-reddening and a heat sensation, usually mild and transient, but sometimes quite unpleasant.

I take pains to explain to patients that, while this may be alarming, flushing is completely benign, and if tolerated, is not a sign of anything untoward. Niacin dilates capillaries, the tiny blood vessels in the surface of the skin. In fact, sometimes niacin is recommended for circulation in conditions like Raynaud's syndrome (In my opinion, it doesn't work that well for poor circulation to hands and feet, since bigger arteries are involved in such conditions).

In fact, just this week on Health Talk I discussed a case report in the Annals of Emergency Medicine in which a group of high school morons shop-lifted some niacin from a health food store and then ingested massive amounts to avoid detection in a drug screening test. That niacin somehow counteracts drug tests is purely the stuff of urban legend, but kids still persist in trying it. Four kids became ill with itching, burning sensations, and a rash.

But the most serious case was that of the ring-leader who chugged eleven tablets and experienced dizziness, vomiting, and heart palpitations. In the ER he was found to be suffering from acidosis, liver failure, and hypoglycemia, which resolved after a few days. Interestingly, despite the elaborate precautions, a drug test performed three days after he was admitted was still positive for marijuana!

Proposed solutions to the niacin flush have included "Time-Release" niacin which I've noticed only delays the flushing and usually doesn't eliminate it. Some studies have even shown that the time-release form of niacin is associated with greater risk of the other major niacin side effect: liver problems.

Then there is "Flush-Free" niacin, usually niacin hexainositol, which in my opinion simply doesn't work ("No pain, no gain"). Studies which support its efficacy use doses like three grams per day, but I rarely see cholesterol budge with niacin hexainosinositol.

Finally there's the advice to take a "Baby Aspirin" a half hour before each niacin administration, but I've found protection to be inconsistent, plus it's a pain to remember the timing, and some people can't or won't take aspirin because of stomach problems.

Meanwhile, drug companies are trying to capitalize on niacin's heart-protective potential by developing a patented process to minimize niacin's flushing effect. A new drug is being introduced by Merck called Cordaptive which teams niacin with a patent super-aspirin called laropiprant; it blocks the release of prostaglandins that cause flushing. Cordaptive may soon be available in 2008, and Merck is counting on it to offset losses caused by the Vioxx debacle, and to recapture some of the lipid market share now dominated by Pfizer's Lipitor.

But interestingly, a cheap natural alternative appears to trump Cordaptive's putative benefits. A new study appearing in the January 28, 2008 edition of the British Journal of Pharmacology reveals that the supplement quercetin is a very efficient flush-blocker when teamed with niacin. Quercetin is a common bioflavonoid found in apples, buckwheat, tea and onions. It is associated with protection from cancer, and blocks the release of histamine from mast cells, making it an ideal allergy blocker.

In the recent study in BJP, rats and humans were given quercetin in doses equivalent to 1000 mg while ingesting niacin. After an average dose of 1750 mg of niacin, quercetin reduced flushing by a whopping 96%! By comparison, aspirin (even at 325 mg) only reduced the flushing by 30%.

In the experiment, quercetin was injected into experimental subjects, so it remains to be seen if oral dosing of quercetin will confer the same benefits, but it certainly is inexpensive and natural, and worth a try if you're taking niacin and are bothered by flushing. Because more quercetin is absorbed via injection than by the oral route, I would recommend two 500 mg capsules of quercetin two or three times daily an hour or so before niacin dosing.

IMPORTANT CAVEAT: Don't try niacin for cholesterol reduction on your own without supervision by a health practitioner. Doses greater than 250 mg per day can cause liver changes in about 5% of patients, and so you need to get your liver function tested along with cholesterol, HDL and triglycerides at one month, three months, and then around every six months to monitor your response to niacin. Just because you don't get flushes, doesn't mean you can't have liver problems, so heads-up!