Fight Cholesterol with Niacin

Posts Tagged ‘LDL’

Good cholesterol may mean little for statin users: Research

Thursday, July 22nd, 2010

Chicago: People with high levels of the so-called good cholesterol HDL tend to have fewer heart attacks. But HDL may offer little protective benefit in people who take statins to lower harmful LDL cholesterol, US researchers said on Wednesday.

An analysis of a large study of healthy people who took AstraZeneca’s statin drug Crestor to prevent heart attacks found that having high HDL was not a good predictor of heart attack risk.

“Once we get LDL into these very low ranges with very potent statins, HDL no longer predicts future risk of heart disease,” said Paul Ridker of Brigham and Women’s Hospital in Boston, whose study appears in the journal Lancet.

The findings raise questions about drugs in development to raise HDL to prevent heart attacks, Ridker added.

Several companies are working on HDL-raising drugs, which might be combined with statins, in the hope of developing even more potent weapons against heart disease.

Tiny Canadian biotech company ResVerlogix has an experimental drug in clinical trials that increases production ApoA-1 in blood, which then raises HDL, a compound that helps ferry harmful fats out of the blood.

Raising HDL through increased ApoA-1 is a different approach from other HDL boosters, such as a class known as CETP inhibitors that included torcetrapib, Pfizer’s most spectacular clinical failure. Merck & Co and Roche are still developing CETP inhibitors.

Current drugs that raise natural levels of HDL, such as niacin, cause unpleasant side effects like flushing.

In the original study, called JUPITER, patients with average to low levels of low-density lipoprotein or LDL were given Crestor or rosuvastatin, which cut their bad cholesterol concentrations to levels seen in aboriginal populations but rarely seen in Western patients.

People in the study who took Crestor had 54% fewer heart attacks and 48% fewer strokes after two years compared to people who took a placebo.

In the new analysis, Ridker and colleagues looked to see if HDL was still a predictor of heart attack risk in people who took Crestor. They found that HDL was still protective in people who got the placebo, but in those whose cholesterol was lowered by the statin, having high HDL made no difference in predicting which patients would have heart problems.

“In my heart of hearts, I believe the only way to address whether or not new agents that increase HDL will be effective is through well-done, carefully taken out clinical trials. There is no other way to get there,” Ridker said.

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Tags: cholesterol, HDL, LDL, niacin, niacin therapy, statin, statins
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Niacin can help raise HDL cholesterol levels

Tuesday, June 1st, 2010

By Tom Valeo, Special to the Times
In Print: Wednesday, May 26, 2010

If we were to compare niacin against all the cholesterol medications, it far and away would have the best profile,” said Dr. John J. Mentel of the Mayo Clinic in Jacksonville. “You get an HDL increase of 15 to 35 percent, depending on which study you look at. Your LDL falls by 10 to 25 percent. And you get a decrease of 20 to 50 percent in your triglycerides. It really is an ideal drug. I think it would be the No. 1 choice if it weren’t for the side effects.

If you’re like most middle-aged Americans, you’ve been concerned about lowering your LDL or “bad” cholesterol.

But raising your HDL or “good” cholesterol might help even more.

The problem is that statins, like Crestor and Lipitor, which can lower LDL dramatically, have very little effect on HDL.

How can you boost your HDL?

By taking niacin, an inexpensive and widely available B vitamin also known as nicotinic acid.

In one recent study reported in the Journal of the American College of Cardiology, patients already taking statins to improve their cholesterol levels boosted their HDL by 23 percent when they took 2,000 milligrams of niacin per day. They also reduced the plaque buildup in their carotid arteries by about 1 millimeter over 12 months.

A study in the New England Journal of Medicine a few months earlier reported similar results. Patients who took 2,000 milligrams of niacin a day raised their HDL by 18.4 percent, and also reduced the plaque buildup in their carotid arteries.

Such results make niacin sound like a drug with enormous potential for reducing heart disease, and that’s precisely how many physicians regard it.

“If we were to compare niacin against all the cholesterol medications, it far and away would have the best profile,” said Dr. John J. Mentel of the Mayo Clinic in Jacksonville. “You get an HDL increase of 15 to 35 percent, depending on which study you look at. Your LDL falls by 10 to 25 percent. And you get a decrease of 20 to 50 percent in your triglycerides. It really is an ideal drug. I think it would be the No. 1 choice if it weren’t for the side effects.”

Side effects?

Niacin at high doses, such as those used in the study, can cause mild liver toxicity in some patients.

“It’s not too different from Tylenol,” Mentel said. “All cholesterol drugs have some liver toxicity associated with them. We monitor that with periodic blood tests. You have to check their cholesterol anyway to see if you’re winning the battle, so you check their liver function at the same time.”

But toxicity is not the only problem. Niacin causes about 10 minutes of intense skin flushing after each dose, which causes many people to stop taking it. Over-the-counter niacin, described as timed-release and “no-flush” forms, reduces this problem dramatically, but doesn’t improve cholesterol levels significantly.

Abbott Laboratories markets an “extended-release” form of prescription-only niacin called Niaspan, which slows the delivery of niacin somewhat, but not so much that it compromises niacin’s beneficial effects. The only problem is the cost. Whereas drugstore.com charges about 8 cents for a 500-milligram tablet of plain niacin, it charges about $2.36 for an equal dose of prescription Niaspan. Prescription drug plans with 90-day refills can offset a great deal of that cost, however.

Pharmacologically the two substances are identical.

“Nicotinic acid is nicotinic acid,” Mentel said.

However, he regularly prescribes Niaspan for his patients because it allows them to take one pill a day with less flushing than they would experience with plain niacin. Also, since Niaspan is considered a drug monitored by the FDA, he can be confident his patients get precisely the dose he prescribes.

“I needed something reliable, and I needed something timed-release to avoid the side effect of flushing if I could,” Mentel said. “Niaspan allows the patient to take one dose, usually at bedtime, which leads to better compliance. That’s the No. 1 problem with using niacin to treat cholesterol: You get poor compliance.”

If you want to take ordinary, inexpensive niacin, you can minimize the flushing by taking it with meals, and by avoiding alcohol, hot beverages or other substances that might cause flushing, according to Dr. Terry A. Jacobson of Emory University School of Medicine, author of How to Beat a Flush, in the most recent Mayo Clinic Proceedings. An ordinary aspirin taken 30 minutes before the niacin also helps reduce flushing, he says, and you can take the niacin just before going to bed so you sleep through the flushing.

Also, increasing the dose gradually over several weeks seems to help some people reduce the flushing, according to Mentel.

“We always start with a small dose and increase gradually,” he said, “but if they build up tolerance and miss a dose or three and start back up again where they left off, they’re going to have trouble again with flushing.”

Before taking niacin, or switching types, talk with your doctor about what kind and how much niacin supplementation might be right for you.

Tom Valeo writes frequently about health matters. He welcomes reader mail but cannot respond to individual queries. You may write him at tom.valeo@gmail.com.

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Tags: cholesterol, HDL, heart disease, LDL, niacin
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The Benefits of Niacin in Atherosclerosis

Wednesday, December 3rd, 2008

(excerpts selected from the full text)

by S. Tavintharan, MD, and Moti L. Kashyap, MD

Cholesterol Research Center, Department of Veterans Affairs
Healthcare System, University of California, Irvine,
5901 East Seventh Street (11/111-I)
Long Beach, CA 90822, USA.
E-mail: moti.kashyap@med.va.gov
Current Atherosclerosis Reports 2001, 3:74–82
Current Science Inc. ISSN 1523-3804
Copyright © 2001 by Current Science Inc.

Niacin favorably alters all major lipid subfractions at pharmacologic doses. Alone or in combination, it promotes regression of coronary artery disease, decreases coronary events, stroke, and total mortality.

Major recent progress in niacin is in four areas. Firstly, recent data indicate that it increases high-density lipoprotein (HDL) and lowers triglycerides and low-density lipoprotein (LDL) by mechanisms different from statins, fibrates, and bile-sequestrants, giving rationale for combination therapy to achieve synergistic effects for complete lipid goal achievement.

Secondly, new data on an extended-release preparation of niacin given once nightly indicates that it is as effective and has greater tolerability than immediate-release niacin.

Thirdly, preliminary data with a single tablet formulation extended-release niacin and an HMG CoA reductase inhibitor (lovastatin) shows it to be safe and very effective, especially for raising HDL.

Finally, emerging evidence indicates that niacin can be used effectively and safely in patients with type 2 diabetes mellitus, who often have low HDL levels.

Introduction
Niacin, an essential B vitamin, has favorable effects on all major lipid subfractions at pharmacologic doses [1•]. Reports of its use in lipid-lowering therapy have been available since 1955 [2]. Although it is a potent lipid modifying agent, its usefulness in the past has been limited by adverse events. Nevertheless, there is renewed interest on the back of convincing data from clinical trials [3–9] and the development and availability of newer formulations of this agent. Tables 1 and 2 highlight the key facts of these clinical trials, which indicate that this agent significantly reduces atherosclerotic cardiovascular disease complications and total mortality.

The Veteran Affairs HDL Intervention Trial (VA-HIT) [10•] showed for the first time that increasing high-density lipoprotein (HDL) cholesterol and decreasing triglycerides (TG) (even without altering low-density lipoprotein [LDL] cholesterol) with gemfibrozil significantly reduced the risk of recurrent major cardiovascular events. The Bezafibrate Infarction Prevention (BIP) study [11] showed similar benefits, significantly in the subgroup with TG greater than 200 mg/dL.

With evidence showing extended-release niacin gives a twofold greater HDL cholesterol increase when compared with gemfibrozil [12•], there is strong rationale for the use of niacin for targeting increases in HDL cholesterol to prevent or reduce progression of atherosclerotic disease.

Efficacy and Toxicity of Niacin
The benefits of niacin in atherosclerosis are not surprising, looking at the broad-spectrum effects on the lipid profile.

Lowering of total cholesterol (TC), LDL cholesterol, very low-density lipoprotein (VLDL) cholesterol, TG, small dense LDL, apolipoprotein (apo) B, and lipoprotein (a) [Lp(a)] are achieved with niacin. In addition, it is also the most potent agent to raise HDL cholesterol, thus favorably reducing the ratios of total cholesterol to HDL cholesterol, and LDL cholesterol to HDL cholesterol, and apo B to apo A1.

The magnitude of cholesterol modification depends on patients’ baseline lipid levels and on the dose and preparation of niacin. On average it lowers LDL cholesterol by 15% to 30%, TG by 20% to 40%, Lp(a) by 30% to 40%, and raises HDL cholesterol by 15% to 30%.

Evidence suggests that antiatherogenic properties for LPAI particles (HDL cholesterol subfraction containing apo AI without apo AII) are greater than LP-AI +AII particles (HDL cholesterol subfraction containing apo AI with apo AII particles) [1•].

Niacin, apart from being the most potent agent in raising HDL cholesterol, has also been shown to improve HDL cholesterol quality by selectively increasing LPAI compared with LP-AI + AII particle concentration in patients with low HDL cholesterol levels [13].

Besides quantitative changes in LDL cholesterol levels, niacin mediates the generation of the more buoyant, less dense LDL particles. Data from observational studies by Austin et al. [14] show that small dense LDL particles are associated with a threefold risk of myocardial infarction (MI), and this is not related to LDL cholesterol levels [15].

The importance of reduction of this LDL subfraction thus assumes greater significance. Hydroxy methyl glutaryl (HMG) CoA reductase inhibitors (statins), which powerfully lower LDL cholesterol, do not decrease small dense LDL concentration [16], whereas fibrates like niacin do [17].

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Tags: cholesterol, Enduracin, HDL, inflammatory markers, LDL, Lipoprotein, lipoprotein-associated phospholipase, niacin
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Effects of Extended-Release Niacin on Lipoprotein Particle Size, Distribution, and Inflammatory Markers in Patients With Coronary Artery Disease .

Thursday, October 9th, 2008

The American Journal of Cardiology , Volume 98 , Issue 6 , Pages 743 - 745
J . Kuvin , D . Dave , K . Sliney , P . Mooney , A . Patel , C . Kimmelstiel , R . Karas

In this study, niacin was added to existing therapy for 3 months in 54 subjects with stable coronary artery disease. Average total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride levels were similar between groups.
Three months of niacin treatment increased total HDL by 7.5% and decreased triglycerides by 15% compared with baseline values (p <0.005 for each), whereas total cholesterol and LDL levels remained unchanged. Addition of niacin resulted in a 32% increase in large-particle HDL (p <0.001), an 8% decrease in small-particle HDL (p = 0.0032), an 82% increase in large-particle LDL (p = 0.09), and a 12% decrease in small-particle LDL (p = 0.008).

Niacin decreased lipoprotein-associated phospholipase A2 and C-reactive protein levels (20% and 15%, respectively, p <0.05 for the 2 comparisons). No significant changes from baseline were seen in any tested parameter in subjects who received placebo.

In conclusion, addition of niacin to existing medical regimens for patients with coronary artery disease and already well-controlled LDL levels favorably improves the distribution of lipoprotein particle sizes and inflammatory markers in a manner that would be expected to confer atheroprotection…
FULL TEXT

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Tags: cholesterol, Enduracin, HDL, inflammatory markers, LDL, Lipoprotein, lipoprotein-associated phospholipase, niacin
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Time-release Niaspan (prescription) compared with plain niacin

Sunday, July 20th, 2008

Equivalent efficacy of a time-release form of niacin (Niaspan) given once-a-night versus plain niacin in the management of hyperlipidemia.Knopp RH, Alagona P, Davidson M, Goldberg AC, Kafonek SD, Kashyap M, Sprecher D, Superko HR, Jenkins S, Marcovina S.

At Northwest Lipid Research Clinic, University of Washington, School of Medicine, Seattle, a study was conducted to compare time-release Niaspan with plain niacin and placebo for the treatment of primary hypercholesterolemia.

The 1998 study was conducted in nine academic lipid research clinics in a randomized, double-blind design. A total of 223 hypercholesterolemic adult men and women participated.

Niaspan 1.5 g at bedtime was compared with plain niacin 1.5 g/d after 8 weeks and 3.0 g/d after 16 weeks in divided doses and with placebo.

After 8 weeks, Niaspan versus plain niacin at 1.5 g/d, the results were very similar for both. Niaspan/plain niacin comparably lowered total cholesterol (C) (8%/8%), triglycerides (16%/18%), low-density lipoprotein (LDL)-C (12%/12%), apolipoprotein (apo B) (12%/12%), apo E (9%/7%), and lipoprotein(a) [Lp(a)] (15%/11%), and raised high-density lipoprotein (HDL)-C (20%/17%), HDL2-C (37%/33%), HDL3-C (17%/16%), and apo A-I (8%/6%) (P < or = .05 in all instances).

After 16 weeks, the Niaspan effect on LDL-C and triglyceride was unchanged while the plain niacin effect approximately doubled.

At equal doses of 1.5 g/d of Niapan versus plain niacin, respectively, AST increased 5.0% versus 4.8% (difference not significant [NS]), fasting plasma glucose increased 4.8% versus 4.5% (NS), and uric acid concentrations increased less, 6% versus 16% (P=.0001).

Flushing events were more frequent with plain niacin versus Niaspan (1,905 v 576, P < .001). Flushing severity was slightly greater with Niaspan, but still well tolerated.

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Tags: cholesterol, HDL, instant-release, LDL, lipid, niacin, Niaspan, time-release
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Benefits of Niacin

Tuesday, July 8th, 2008

The Robert Kowalsky Youtube interview provides an interesting overview of the benefits of niacin therapy.

Large doses of niacin (as nicotinic acid, but not the niacinamide form) are prescribed to combat high blood pressure and to broadly improve blood cholesterol levels. Niacin is used to treat high Cholesterol because of its unique ability to improve lipid profiles for ApoB, LDL, small dense LDL, HDL, HDL2b - an extremely good cholesterol, Lp(a), fibrinogen and trigycerides. Pharmacologic doses of niacin (1.5 to 6 grams/day in divided doses) typically reduce LDL cholesterol levels by 10 to 25 percent and triglyceride levels by 20 to 50 percent. HDL cholesterol levels are also typically increased by 15 to 35 percent.

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Tags: apoB, cholesterol, fibrinogen, HDL, HDL2b, LDL, Lp(a), niacin, small dense LDL, trigycerides
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Is anything wrong with words-of-caution? That depends.

Monday, May 19th, 2008

The unfortunate result of well-meaning, erroneous words-of-caution, regarding the therapeutic use of niacin, is that some people are made fearful, and some will adopt a less effective, more expensive alternative.

Niacin has been successfully controlling blood, lipid ratios for almost sixty years. The medical community has increasingly recognized niacin as an effective, if not the most effective, end-result medication for achieving healthful, blood ratios.

Often, when niacin is recommended as an alternative to statin drugs, certain caveats, words-of-caution, are included. These two most common warnings, which are usually presented as well-established “facts,” are questionable.

1. Therapeutic doses of niacin can cause liver damage, so regular blood tests should be taken.
2. Therapeutic doses of niacin are not suitable for diabetics, as niacin raises glucose levels.

The confusion between facts and information that is erroneously considered to be factual is discussed in FACTS AND FACTOIDS: An Information Sheet for Patients by Abram Hoffer MD PhD FRCP(C).

Fact: Something that has really occurred or is the case: hence a datum of experience, as distinct from conclusions. Loosely defined, something that is alleged to be, or might be a “fact.”

Factoid: A factoid is a fact that never existed before it appeared in print, but has been reprinted ever since. It is truly launched if it first appears in a reputable medical journal like the Journal of the American Medical Association and republished in the New York Times which gives it international stature. A factoid, using simple Anglo Saxon terminology, is a lie, and like many lies and misconceptions, once it has been published develops a life of its own and is reprinted over and over, from textbook to textbook. The best example is the lie (factoid) that vitamin C causes kidney stones.

Below is another excerpt from FACTS AND FACTOIDS pertaining to therapeutic doses of niacin.

About Megadose Niacin
The factoid niacin causes liver damage is analyzed thoroughly by William Parsons Jr, who shows that niacin will often increase liver function tests but that these increases do not arise from liver pathology.

Since I began using mega-doses of this vitamin in 1952, I have seen a few cases of obstructive-type jaundice which cleared when niacin was stopped, and in one case I had to resume the use of niacin because the patient’s schizophrenia recurred. He recovered, and the jaundice did not recur.

I have seen so few cases of jaundice that there is little evidence that the jaundice arose from the use of the niacin. Jaundice has a natural occurrence rate, and from any series of patients a few will get jaundice from other factors.

In rare cases too much niacin causes nausea and vomiting, and if this persists because the niacin is not decreased or stopped the dehydration might be a factor. I have seen no cases in the past fifteen years. The main danger from taking niacin is not jaundice; it is that people will live longer.

Below is an excerpt from Is niacin okay for people with diabetes? by Julie K. Silver, M.D., Harvard Medical School. Here, Dr. Silver puts the word-of-caution regarding niacin & diabetics into an updated perspective.

In the mid-1980s, a few small studies showed that high doses of niacin increased blood sugar levels among people with diabetes or pre-diabetes. This work prompted the American Diabetes Association to recommend that the drug be used cautiously, at doses under 2 grams a day, and with frequent blood sugar monitoring. Many doctors took this to mean that niacin shouldn’t be used by people with diabetes.

Since then, two large trials have shown that niacin has only small, if any, effects on either blood sugar or hemoglobin A1C, a kind of time-lapse test that gauges blood sugar levels over the previous three months. One of these trials used over-the-counter crystallized niacin; the other used a once-a-day, prescription version.

…Ask your doctor to rethink his or her stance on niacin. The American Diabetes Association now recommends its use by people who have low HDL. With a little extra attention to blood sugar, this drug may help people with diabetes improve their cholesterol levels and help prevent an all too common consequence of diabetes — heart disease.

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Tags: cholesterol, diabetic, HDL, LDL, lipids, niacin
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Don’t misinterpret cholesterol reports.

Monday, January 7th, 2008

December 20, 2007 12:35 am

Don’t misinterpret cholesterol reports.

The Associated Press recitation of a Centers for Disease Control and Prevention report is a killer of an article and should be revoked in favor
of a healthy discussion of cholesterol [”Cholesterol check:Americans doing OK,” Dec. 13].

READ FULL TEXT PDF

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Tags: cholesterol, Cholesterol check, discussion, HDL, healthy, LDL, lower cholesterol
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First presented in 1999 to leading cardiovascular specialists in Moscow, Russia

Saturday, December 8th, 2007

Wax-Matrix Sustained-Release Nicotinic Acid

Joseph M. Keenan, M.D.
Professor, University of Minnesota
Department of Family Practice

INTRODUCTION:
Today we have more options than ever for the pharmacological management of hyperlipemia. Some of the newer agents have unprecedented potency in lowering LDL cholesterol while others may be better at reducing triglycerides or improving HDL. Keeping track of which drugs are best for which lipid problems can be a challenge in the everyday practice of medicine. I offer here a simple rationale for selecting a first choice in lipid management. If you follow this rationale I think you will find that nicotinic acid or niacin is the best first choice, and that among the niacin preparations wax-matrix CNA (controlled release niacin) is by far the best available.
SELECTING A LIPID LOWERING DRUG:. . .

FULL TEXT _ PDF

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Tags: cholesterol, controlled release, Enduracin, HDL, hyperlipemia, LDL, lipid management, lipoproteins, niacin, nicotinic acid, triglycerides, Uncategorized, Wax-matrix
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