Niacin: Immediate release OTC works best. www.theheart.org

Dec 22, 2003

Cheapest preparations of over-the-counter niacin most effective at lipid lowering

Seattle, WA - Many over-the-counter niacin preparations may have no free nicotinic acid (vitamin B3)the lipid-lowering component for which the product is often marketedwhile others may have too much, according to a new study. A survey of 29 over-the-counter products indicated that the unregulated products contain variable doses of niacin; in some cases they contain no nicotinic acid, and in others they have high concentrations of the agent, which could produce liver toxicity.

The paper appears in the December 16, 2003 issue of the Annals of
Internal Medicine.[1]

As Dr C Daniel Meyers (Veterans Affairs Medical Center, Long Beach,
CA) and colleagues explain in their paper, niacin was one of the first agents found to lower LDL and triglycerides while boosting HDL when given in daily doses of 1000 to 4000 mg. Large clinical trials also showed it to reduce cardiovascular events. Nicotinic acid was never widely used, however, because of side effects, primarily "niacin flushing": redness, itching, burning, and paresthesias, which set in within 10 to 15 minutes of ingestion and last up to an hour. The frequency and severity of these episodes decrease over time with repeated doses, and niacin is thus available over the counter in the
US as a dietary supplement, unregulated by the US FDA.

Meyers et al decided to take a closer look at over-the-counter preparations being marketed as niacin after witnessing a series of hyperlipidemic patients reporting to the University of Washington
Medical Center Lipid Clinic in Seattle having failed to respond to over-the-counter niacin therapy.

When cheaper is better
The researchers calculated the monthly cost for each of 29 preparations bought from pharmacies, health-food stores, or over the internet. They then used high-performance liquid chromatography to measure the free nicotinic acid content. Three types of preparations were evaluated: immediate-release, sustained-release, and no-flush formulations. The researchers found that the no-flush preparations were the most expensive, followed by the sustained-release preparation, at less than half the cost, then the slightly cheaper immediate-release niacin preparations. Ironically, the most expensive no-flush preparations were found to have no free nicotinic acid, whereas the sustained-release and immediate-release preparations had comparable nicotinic acid contentsthe cheap, immediate-release versions containing the most.

Cost and contents of niacin preparations No flush Sustained release Immediate release
Cost per month ($) 21.70 9.75 7.10
Average nicotinic acid content (mg) 0 502.6 520.4
"No-flush niacin is the most expensive of the niacin preparations yet contains no free nicotinic acid and should not be used to treat dyslipidemia," Meyers et al conclude. "Sustained-release brands are inexpensive and contain a full amount of free nicotinic acid, but several preparations have been associated with increased hepatotoxicity."

Of note, the FDA has approved two prescription brands of niacin, one a sustained release (Niaspan®; Kos Pharmaceuticals, Miami, FL) and the other an immediate release (Niacor®; Uspher-Smith, Minneapolis, MN), but as the authors point out, these two drugs are considerably more expensive than the over-the-counter alternatives.

For people wishing to try niacin for lipid lowering, the authors recommend immediate-release over-the-counter niacin brands such as those made by Rugby Laboratories (Westbury, NY), since many of these contain the full amount of nicotinic acid and immediate-release niacin is the only form of the agent shown to prevent cardiovascular disease and death in clinical trials. As well, Meyers et al advocate baseline laboratory tests for fasting glucose, liver aminotransferase levels, and uric acid in all patients before niacin therapy begins, repeated six to eight weeks later and after any dose increases.

I did some investigation on this study and believe it to be terribly flawed.
No-flush niacin is also known as insitol hexaniacinate, inositol hexanicotinate and inositol nicotinate. It is a compound with an inositol molecule in the center and 6 niacin (nicotinic acid) molecules bound to it.
It is absorbed intact and hydrolyzed in the body with release of free niacin (nicotinic acid) and inositol. It appears to be metabolized slowly and peaks at about 10 hours in the serum. Inositol is frequently used as a carrier molecule of other agents. This form of nician is approved in Britian for the treatment of dyslipidemia. In this study, the no-flush, large inositol hexaniacinate molecule would simply not pass through the HPLC column as would a single nicotinic acid molecule. In my opinion, I believe the author's findings are correct, but their conclusions are unjustified.

Arzneimittelforschung. 1979;29(12):1859-62.
Enzymatic hydrolysis of pentaerythritoltetranicotinate and meso-inositolhexanicotinate in blood and tissues.
Harthon L, Brattsand R.

The esters between nicotinic acid and pentaerythritol (niceritrol, Perycit)
or meso-inositol (MIHN) were hydrolyzed by enzymes present in plasma and tissues of man, rat and dog. Human plasma and rat tissues hydrolyzed niceritrol at a higher rate than did MIHN. The reversed relation was found with dog tissue. The ability of niceritrol and MIHN to raise the level of free nicotinic acid of plasma was studied on man, dog and rat and related with their hydrolysis in vitro and the different solubility of the esters.
There was a relationship between these properties of the esters and their ability to increase the plasma level of nicotinic acid.

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Dec 22, 2003

Cheapest preparations of over-the-counter niacin most effective at lipid lowering

Seattle, WA - Many over-the-counter niacin preparations may have no free nicotinic acid (vitamin B3)the lipid-lowering component for which the product is often marketedwhile others may have too much, according to a new study. A survey of 29 over-the-counter products indicated that the unregulated products contain variable doses of niacin; in some cases they contain no nicotinic acid, and in others they have high concentrations of the agent, which could produce liver toxicity.

The paper appears in the December 16, 2003 issue of the Annals of
Internal Medicine.[1]

As Dr C Daniel Meyers (Veterans Affairs Medical Center, Long Beach,
CA) and colleagues explain in their paper, niacin was one of the first agents found to lower LDL and triglycerides while boosting HDL when given in daily doses of 1000 to 4000 mg. Large clinical trials also showed it to reduce cardiovascular events. Nicotinic acid was never widely used, however, because of side effects, primarily "niacin flushing": redness, itching, burning, and paresthesias, which set in within 10 to 15 minutes of ingestion and last up to an hour. The frequency and severity of these episodes decrease over time with repeated doses, and niacin is thus available over the counter in the
US as a dietary supplement, unregulated by the US FDA.

Meyers et al decided to take a closer look at over-the-counter preparations being marketed as niacin after witnessing a series of hyperlipidemic patients reporting to the University of Washington
Medical Center Lipid Clinic in Seattle having failed to respond to over-the-counter niacin therapy.

When cheaper is better
The researchers calculated the monthly cost for each of 29 preparations bought from pharmacies, health-food stores, or over the internet. They then used high-performance liquid chromatography to measure the free nicotinic acid content. Three types of preparations were evaluated: immediate-release, sustained-release, and no-flush formulations. The researchers found that the no-flush preparations were the most expensive, followed by the sustained-release preparation, at less than half the cost, then the slightly cheaper immediate-release niacin preparations. Ironically, the most expensive no-flush preparations were found to have no free nicotinic acid, whereas the sustained-release and immediate-release preparations had comparable nicotinic acid contentsthe cheap, immediate-release versions containing the most.

Cost and contents of niacin preparations No flush Sustained release Immediate release

Cost per month ($)
21.70 9.75 7.10

Average nicotinic acid content (mg)
0 502.6 520.4

"No-flush niacin is the most expensive of the niacin preparations yet contains no free nicotinic acid and should not be used to treat dyslipidemia," Meyers et al conclude. "Sustained-release brands are inexpensive and contain a full amount of free nicotinic acid, but several preparations have been associated with increased hepatotoxicity."

Of note, the FDA has approved two prescription brands of niacin, one a sustained release (Niaspan®; Kos Pharmaceuticals, Miami, FL) and the other an immediate release (Niacor®; Uspher-Smith, Minneapolis, MN), but as the authors point out, these two drugs are considerably more expensive than the over-the-counter alternatives.

For people wishing to try niacin for lipid lowering, the authors recommend immediate-release over-the-counter niacin brands such as those made by Rugby Laboratories (Westbury, NY), since many of these contain the full amount of nicotinic acid and immediate-release niacin is the only form of the agent shown to prevent cardiovascular disease and death in clinical trials. As well, Meyers et al advocate baseline laboratory tests for fasting glucose, liver aminotransferase levels, and uric acid in all patients before niacin therapy begins, repeated six to eight weeks later and after any dose increases.