Please adopt this vitamin - drug.

Please Adopt This Vitamin

Niacin is an orphan. Not literally, of course. A true orphan drug is one that helps too few people to be profitable. On the contrary, niacin can help millions of people who can't lower their cholesterol enough by diet alone.

What makes niacin orphan-like is that, legally, it's not a patentable drug, but a vitamin. That makes it unprofitable for companies to find out how to make the safest, most effective niacin tablet ... or to advertise the product once they've go it.

"To compare one type of niacin with another takes a large, well-designed study," says Basil Rifkind of the National Heart, Lung and Blood Institute (NHLBI). "But the financial incentive is not great, because no one has a patent on niacin."

Now two new developments are making it even more critical that someone investigate niacin: With health-care costs rising and coverage by private insurers (and possibly Medicare) shrinking, a cheap drug like niacin looks increasingly more attractive than costly cholesterol-lowering drugs like lovastatin or gemfibrozil.

Second, doctors have reported nearly a dozen cases of hepatitis, or inflammation of the liver, in people taking some kinds of niacin.

"If as much thinking went into niacin as has gone into gemfibrozil or lovastatin, we'd know how it works and why some types cause liver damage," says Roger Illingworth of the Oregon Health Sciences Center in Portland. "We should be trying to find out."

Niacin's Advantages. Niacin has a lot going for it.

"It's the longest known and least expensive drug [for lowering cholesterol]," says Joseph Keenan of the University of Minnesota. "And it has the best track record for safety."

Indeed, niacin is considered a "drug of first choice" by the National Cholesterol Education Program. Here's why:

* Niacin lowers total and LDL ("bad") cholesterol. But unlike all other cholesterol-lowering drugs except gemfibrozil, it also lowers harmful triglycerides and raises HDL ("good") cholesterol. (1)

* More than 1,000 middle-aged male heart-attack victims who took niacin for five years as part of the Coronary Drug Project were less likely to have died of another heart attack--nine years after the study ended. (2)

* Niacin is cheap. The NHLBI estimated these wholesale yearly costs for five cholesterol-lowering drugs:(1)

Lovastatin $900 Niacin (by prescription) $700 Cholestyramine or colestipol $500-550 Gemfibrosil or probucol $375 Niacin (over-the-counter) $50

With so many advantages, you'd think niacin would be the biggest selling cholesterol-fighter on the market.

Yet prescription sales are dwarfed by gemfibrozil and lovastatin, which have each captured about 30 percent of prescriptions. (3) And over-the-counter sales for niacin, estimated at $25 million, have declined since 1989, says the Council for Responsible Nutrition, an association of vitamin-makers.

That's plenty because the system is biased against niacin. There aren't ads in medical journals or travelling salesmen from drug companies urging doctors to use it. "When you look at the advertising for a drug like and advertising for a drug like lovastatin or gembrozil, there's no comparison," says the NHLBI's Rifkind.

Then there are niacin's side effects.

The Down Side. Niacin's most common side effect is no secret. Most people who take, say, a 500-milligram dose of regular niacin, experience flushing, a tingling sensation accompanied by a red skin rash.

"Physicians have shied away from niacin because patients get upset," say Minnesota's Keenan.

But the flushing can be minimized. Gradually increasing the dose, taking the drug with meals and not with hot liquids, and taking an aspirin 30 minutes before the niacin all help to reduce the rash. After several weeks, many people no longer have flushing...if they're willing to wait that long.

"The physicians who like niacin know how to take patients through the side effects," says Rifkind.

Apparently most doctors aren't in the know about niacin, because up until a few years ago, it wasn't very popular. Then, in 1987, came Robert Kowalski's The 8-Week Cholesterol Cure, advising people to take timed-release niacin.

Because the timed-release preparations let niacin enter the bloodstream more slowly, flushing didn't occur. Sales soared...then dropped.

Timed-Release Troubles. In 1988, 16 people sued Kowalski for not adequately warming them that the timed-release niacin he recommended could cause hepatitis. (The lawsuits are still pending.)

Meanwhile, medical journals reported that five patients taking timed-release niacin developed hepatitis. In one report, three people who took 2,000 to 4,000 mg a day had only mild hepatitis. One was nauseated and fainted after drinking a glass of champagne, another got jaundice, all had abnormal results on liver-function tests, and all got better when they switched to regular niacin. (4)

"We've had four other patients with hepatitis who were not mentioned in the report," says its author, Yaakov Henkin of the University of Alabama.

Henkin's patients were lucky. In other cases, a 32-year-old man who took only 500 mg a day of timed-release niacin developed not only liver, but kidney failure, and was temporarily unable to breathe without a ventilator. Another patient, who took a daily dose of 6,000 mg, required a liver transplant.

The news jolted the vitamin-supplement industry, already reeling from lawsuits filed by trytophan-taker who got eosinophilia-myalgia syndrome. This past August, the Council for Responsible Nutrition advised its members to temporarily stop selling temed-release niacin.

"Several of the large companies have discontinued the product," says CRN's Annette Dickinson.

Meanwhile, Oregon's Roger Illingworth wrote to his state's pharmacists, warning that timed-release niacin is worse than regular niacin for livers.

How could that be? "We speculate that regular niacin is only in the blood for a short time, so it allows liver enzymes to recuperate, while timed-release niacin does not," says Alabama's Henkin.

But that's just speculation, he adds. no one really knows.

Pick A Brand, Any Brand. That's not all no one really knows about niacin.

Before a drug hits the market, the manufacturer has to find out how well it does what it's supposed to do and how often it causes adverse effects. Drugs also have to be made using an approved formula.

Not so with niacin. It can be made "any old way you want," says Ralph Shangraw of the University of Maryland School of Pharmacy. That's not a problem with regular niacin, because it's easily dissolved and absorbed. But timed-release niacin is a different story.

Some brands, like Endur-Acin, an inexpensive product recommended by Kowalski, use wax to keep the niacin from dissolving too quickly. Others, like Rorer's Nicobid, use tiny beadlets that are coated with different thicknesses of shellac. And there are many other possibilities, each of which affects how well the niacin is absorbed and how well people tolerate it.

In study co-authored by Frank Sacks of Harvard University, people who took Endur-Acin got twice as much of the niacin as people who took Nicobid, which is more expensive because it's only available by prescription. (5)

Furthermore, says Sacks, "In one study, Nicobid caused only a little less flushing, but a lot more stomach upset than regular niacin. (6)

"I've been giving niacin to patients for seven years, and the only brand I've ever used is Endur-Acin," he adds.

That's not to say Endur-Acin is the best timed-release niacin on the market. No one knows precisely how often it causes liver problems.

But at least there are published studies showing that it is well-absorbed. And a new study by Minnesota's Keenan (funded) by Endur-Acin's manufacturer, Innovite) shows that it lowers cholesterol by 11 percent in people under 50 and by 22 percent in older people. (7)

Most brands have never been tested in human studies.

Getting to Know Niacin. "It's a helter-skelter situation," says Harvard's Sacks. "Because niacin is classified as a vitamin, all we have are anecdotes."

But reclassifying niacin that's sold in high doses as a drug would make it more expensive. And anyway, the law prohibits the FDA from doing that.

Still, the government could fund studies to answer these pressing questions:

* How often and why does niacin harm the liver? Is it worse than lovastatin, which also causes liver problems?

* Are all timed-release formulations equally risky?

* Would livers be safest with a tablet that dissolves slowly enough to prevent flushing, but quickly enough to give the liver a chance to recuperate before the next dose?

Then the government could pass on its findings to doctors, because no one else will.

"Niacin is greatly under-utilized as a treatment for high cholesterol," says Sacks. And that's a shame, adds NHLBI's Rifkind, because "niacin could save patients and insurance companies a lot of money."

(1) Arch. Intem. Med. 148: 36, 1988.

(2) J. Am. Coll. Cardiol. 8: 1245, 1986.

(3) J. Am. Med. Assoc. 263: 2185, 1990.

(4) J. Am. Med. Assoc. 264: 181, 241, 1990.

(5) J. Clin. Pharmacol. 28: 1136, 1988.

(6) Metab. 34: 642, 1985.

(7) American Geriatric Society meeting, May 1990.