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Home / Juvenon Health Journal / Niacin: Is the First Cardio Health Therapeutic Still the Best?

 

Juvenon Health Journal volume 11 number 4 – June 2012

By Benjamin V. Treadwell, Ph.D.

Most of us are aware of the health problems attributed to high cholesterol and the other lipid (fatty) blood constituent, triglycerides. No wonder drugs formulated to control blood levels of lipids have become big business for the pharmaceutical industry.

Some critical questions remain unanswered, however. For example, why are elevated blood lipids unhealthy? What evidence supports their potential to cause health problems? Are the drugs prescribed to improve lipid levels safe? You may be surprised by the answers (or lack thereof), the subject of this issue of the Health Journal.

Heart of the Matter

Many decades ago, the medical profession realized blocked arteries had something to do with one of the more common causes of death. They linked the condition, especially in the arteries supplying the heart, with heart attacks (myocardial infarctions).

Autopsies showed an abundance of deposits on the cells lining the arteries, as well as an overgrowth of smooth muscle cells beneath the lining. This buildup diminished the diameter of the vessel, consequently decreasing the flow of blood that carries nutrients to the hard-working heart muscle.

Pathologists identified many of the deposits as fats. Their findings evolved into a hypothesis, blaming the development of constricted arteries, atherosclerosis and accompanying heart attacks on excess fats in the blood. Particularly hazardous? Fats that are not very soluble and tend to form deposits, like cholesterol.

The solution to this health problem seemed to be straightforward: simply lower the blood levels of these lipids to prevent arterial deposits. And so, the search for lipid-lowering agents began.

Why Not Niacin?

Remember the old saying, “First impressions are often the most accurate”? We may find it applies to the therapeutics for abnormal serum lipid levels (dyslipidemia). Nearly 60 years ago, doctors prescribed niacin (nicotinic acid or B3), a simple vitamin, to lower triglycerides and cholesterol. The results were impressive when patients followed the therapy. (See Juvenon Health Journal, Volume 8, Number 12, “Cardiovascular Health: How Vitamin B-3 Can Make It Better.”)

Unfortunately, in the 1950s, the rate of compliance tended to be low. Patients did not like the side effects of the mega doses (1,000-4,000 mg/day of niacin) required. The uncomfortable, hot-flushing sensation and itching could last 30 minutes to an hour.

Enter Big Pharma


The pharmaceutical industry saw the market potential for a cholesterol-lowering drug… especially one that did not have niacin’s uncomfortable side effects. Their laboratories moved quickly to develop compounds that would block an enzyme involved in synthesizing the lipid. The early compounds, designated statins, included many different varieties, some still on the market today.

(Aside: for hundreds of years, the Chinese have been using a naturally fermented rice product, red yeast rice, for cardiovascular health. It contains the same molecule, lovastatin, synthesized by the chemists in the early development days).

The new statin drugs proved very effective at reducing total cholesterol levels and, seemingly, lowering related cardiovascular mortality rates. But this is only the first chapter of the story of serum cholesterol and statin-associated improvement in cardiovascular health.

Particle Size Matters

Cholesterol and triglycerides are carried in the blood stream bound to specific molecules known as lipoproteins. Imagine particles of varying size, some very large and others small and dense. The size is associated with the amounts of lipids (and other components) they contain.

Very recent research shows there are large, medium and small particles of low-density lipoproteins (LDL), carrying “bad cholesterol,” and high-density lipoproteins (HDL), carrying “good cholesterol.” There seems to be a correlation between the larger particles, especially HDL, and better health. An increase in small dense particles, particularly LDL, has been linked to coronary artery disease (CAD).

The Bad, The Good and The Niacin

Remember, the statin drugs are effective at reducing the total amount of cholesterol. That’s right, no distinction between the bad LDL and the good HDL. Now flash back to the early cholesterol-lowering star, high doses of niacin.

More research has demonstrated the vitamin not only reduces LDL, as well as triglycerides, but also significantly increases HDL. And that’s not all. According to recent studies, niacin also improves the size of the HDL particle, another plus for cardiovascular health not found with statins. But what about the hot flush and itching caused by the mega doses?

Controlling the Itch

Those unpleasant side effects are the consequence of niacin binding to a specific receptor (GPR109a), present on inflammatory cells (monocytes/macrophages), fat cells, and skin cells (Langerhans cells and keratinocytes). The receptor activates the synthesis of hormone-like substances, the prostaglandins, which, in turn, act on the tissues in the immediate area to produce the flush and itchiness.

Taking aspirin, an inhibitor of prostaglandins synthesis, can reduce the side effects. But the hormone’s synthesis appears to be an important response for maintaining biological balance or homeostasis. For example, evidence indicates it helps prevent an increase in the accumulation of clot-forming platelets.

(Aside: An anti-inflammatory medication, Vioxx, was actually recalled from the market, partially due to its interference with the normal production of PGI2, a prostaglandin that improves vascular health and prevents stroke.)

Happily, an extended release (ER) form of high-dosage niacin was developed. It works as well as regular vitamin B3 for improving lipid health. It triggers the GPR109a receptor and its positive health effects. And, because it slowly releases the niacin from a patented waxy-mixture, it significantly reduces the intense flushing/itching when regular niacin is quickly released into the blood stream.

More HDL, Less Inflammation

So, without the irritating side effects, patients are more likely to comply with niacin therapy, increasing their levels of HDL. What makes this a health benefit?

HDL acts as a vehicle to carry excess cholesterol from the tissues of the body to the liver for processing and elimination. (See Juvenon Health Journal, Volume 7, Number 6, “Niacin: a Comeback for the Happy Cholesterol Vitamin.”) There is some evidence the lipid may have anti-inflammatory qualities as well.

For example, an antioxidant, PON-1 (paraoxonase-1), occurs in the blood attached to the HDL particle. People with CAD often have low levels of this enzyme, suggesting higher levels contribute to healthy arteries. PON-1 may also help prevent the oxidation of other lipids, such as LDL, reducing the incidence of arterial inflammation.

As a “bonus,” if you will, niacin itself may help inhibit inflammation. According to recent findings, by binding to the GPR109a receptor, niacin interferes with production of inflammatory agents (cytokines, TNF alpha, IL-6, MCP-1) associated with atherosclerosis and CAD.

Cholesterol Controversies


From niacin to statin drugs, the initial quest for effective, lipid-lowering therapeutics seems to have been successful. But is this approach really responsible for the coinciding improvements in arterial/cardiovascular health? Some scientists believe cholesterol actually has little to do with it. Some even go so far as to say lowering lipids is useless and may even damage our health.

At least for the statin class of therapeutics, evidence is mounting to support their role in improving cardiovascular health by reducing immune system activity and related inflammation. This anti-inflammatory effect may be the primary function of statins. In other words, developing them as lipid-lowering agents may have simply been serendipitous.

But, before we all jump on the statin bandwagon, we should be aware of the potential side effects. According to recent warnings issued by the FDA, they include (but are not limited to) muscle ache, especially with exercise (may be associated with potentially life-threatening skeletal muscle deterioration), memory loss and liver damage.*

Weighing the Alternatives

Do excess small particles of LDL cholesterol in the blood stream lead to CAD? Or is inflammation the real culprit? Are the risks of taking statins not worth the rewards? Clearly, there are more chapters to the story of therapeutics for controlling cholesterol blood levels and/or inflammation.

In the meantime, extended release niacin seems to be a good choice as it addresses both conditions. Some medical professionals offer another alternative (mentioned in an earlier aside). Studies show red yeast rice, a natural statin, lowers LDL and total cholesterol with fewer side effects than the synthetic statins.

Perhaps the best solution is a combination, suggested by recently published research: red yeast rice and extended release niacin, both available over the counter. Of course, you’ll want to consult your health professional before deciding, which, if any, therapeutics are appropriate for you.

disclaimer

*Metabolized by the liver, as are many drugs, niacin may also cause liver damage.


Ask Ben

Dr. Treadwell
answers your questions.

question: A recent blood test analysis showed that my total cholesterol and triglycerides were elevated. The report also emphasized that my LDL (bad cholesterol) was above normal, and the so-called good HDL (or, as I like to call it, my “happy cholesterol”) was on the low end of the normal range. Is it possible to take some natural supplements to improve these lipids and return them to more healthy levels? -SA

answer:Cholesterol is a somewhat complex subject. It is actually necessary for the construction of several cellular components. But, as you know, high LDL (low density lipoprotein) levels are usually associated with health problems. High HDL (high density lipoprotein) levels, on the other hand, seem to indicate good cardiovascular health.

Health professionals often prescribe statin drugs to lower LDL. But studies have identified other options with few (if any) side effects, including aerobic exercise and omega-3-rich fish oil.

Niacin (vitamin B-3) is another relatively inexpensive, over-the-counter possibility. As early as the mid-1950s, research showed it was an effective lipid-lowering agent. According to more recent findings, niacin also helps raise HDL levels. (See Juvenon Health Journal, Volume 8, Number 12, “Cardiovascular Health: How Vitamin B-3 Can Make It Better” and Volume 7, Number 6, “Niacin: A Comeback for the Happy Cholesterol Vitamin.”)

In an extended-release form, niacin seems to be well tolerated by most people. I’d recommend starting with a 500-mg/day dose after consulting with your health professional, of course. He/she may suggest periodic blood tests to determine if the niacin is affecting your liver function, one of the vitamin’s few potential side effects.

Send your questions to AskBen@juvenon.com.
For more questions and answers, click here.

Dr. Benjamin V. Treadwell is a former Harvard Medical School professor and member of Juvenon’s Scientific Advisory Board.


Research Update

A research team from the University of Illinois School of Medicine, nearby CGH Medical Center and Abbott Laboratories, compared two approaches to lipid profile therapy based on data from a multi-center clinical trial. They published their findings in a recent issue of Vascular Health and Risk Management.

Results from the trial, known as the “SUPREME Study,” included the effects of two LDL cholesterol-lowering therapies on the number and size of HDL particles in blood. The 137 subjects were divided into two groups. One took 40 mg/day of a commonly prescribed cholesterol-lowering statin drug, Simvastatin (S). The other group took the same dose of S plus 1000-2000 mg of a vitamin, extended release niacin (NER/S).

Using nuclear magnetic resonance spectroscopy, the SUPREME Study team recorded HDL particle numbers and size for each subject before the start of the study to establish a baseline. They repeated the measurements at the end of the 12-week experiment.

The Illinois researchers’ analysis clearly showed a more pronounced positive effect from the NER/S protocol than the S alone. The combination therapy promoted a significant decrease in the number of HDL particles and a corresponding increase in their size. Previous research had already established that larger HDL particles predict a lower incidence of cardiovascular disease.

An earlier study also demonstrated niacin’s capacity to reduce markers of inflammation associated with cardiovascular disease. Other research has attributed lower LDL (the so-called bad cholesterol) and triglyceride levels to the vitamin.

These findings, along with the Illinois team’s on HDL, support niacin’s health benefits. Either alone or in combination with a statin drug, it seems to have the potential to improve lipid profiles and cardiovascular health.

Read abstract Here

This Research Update column highlights articles related to recent scientific inquiry into the process of human aging. It is not intended to promote any specific ingredient, regimen, or use and should not be construed as evidence of the safety, effectiveness, or intended uses of the Juvenon product. The Juvenon label should be consulted for intended uses and appropriate directions for use of the product.

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