Juvenon Health Journal volume 8 number 12 december 2009
By Benjamin V. Treadwell, Ph.D.
As we age, our healthcare professionals are likely to recommend not only a healthy diet and exercise, but also specific medications to improve particular health markers. With the evidence linking elevated cholesterol levels to increased risk of cardiovascular disease, one of the more common prescriptions is a drug to lower cholesterol.
Is that really all there is to it? Many of the pharmaceutical companies initially believed the answer was an unequivocal “yes.” They devoted a significant amount of money and manpower to an intense pursuit of therapeutics that lower blood cholesterol. But, even as they succeeded, they began to realize the answer is not so simple, let alone unequivocal.
A relatively insoluble compound, cholesterol is required for the construction of numerous cellular components. So, we need it for survival. However, because of their insoluble nature, cholesterol molecules must be carried via the blood stream in specialized vehicles – lipoproteins – with specific destinations.
The two major cholesterol-carrying vehicles are LDL, an intermediate-density lipoprotein, and HDL, a high-density lipoprotein. (VLDL, a very low-density lipoprotein, can be trimmed by specific enzymes and converted to LDL.)
LDL is transported from the liver to the tissues of the body where it docks on specific cellular receptors and, subsequently, unloads its cholesterol to that cell. HDL, on the other hand, travels in the opposite direction. It picks up cholesterol from the peripheral tissues and delivers it to the liver, where it is metabolized and excreted in bile.
LDL in Excess
When there is an excess of LDL cholesterol in the blood, this vehicle tends to become too prevalent in tissues, such as the delicate cells (endothelial cells) lining the walls (intima) of arteries. Under these conditions, an oxidant, a free radical, for example, is more likely to interact with it. The oxidized LDL vehicle, now rancid, sets off an alarm that activates the transformation of specific cells, monocytes, into inflammatory cells, macrophages.
So begins an inflammatory reaction, which produces molecules (cytokines) that, in turn, draw in additional monocytes. Left unchecked, this sequence creates deposits of fat, forming a plaque (atheroma) that narrows the artery and decreases blood flow. The atheroma can also break-off and travel in the vessels until it reaches a small artery where it can block blood flow completely, causing a coronary infarction (heart attack).
The Rest of the Story
In general, high LDL cholesterol levels are associated with disease, while high HDL seems to indicate good cardiovascular health. This seems logical since the HDL takes cholesterol from the peripheral tissues to the liver for removal, and the LDL does the opposite.
When it comes to total cholesterol (HDL + LDL), a high number can also be positive, as long as the HDL dominates the ratio. So, returning to our original question, shouldn’t cholesterol-lowering pharmaceuticals be the easy answer to healthier LDL levels and a better ratio? Not according to an impressive recent study.
Ezetimibe vs. Vitamin B-3
Physicians and scientists at a number of medical centers examined the effects on cardiovascular health of a relatively new LDL cholesterol-lowering drug, ezetimibe, as compared to a common vitamin, B-3 or niacin, known for increasing HDL cholesterol.
They conducted a human trial with 208 patients who had cardiovascular disease or were at high risk, all already taking cholesterol-lowering statin drugs. Half of the patients were also prescribed ezetimibe, while the other half took niacin.
The comparative cholesterol results? A significant increase in HDL in those patients taking niacin and no increase (in some cases, a decrease) for the ezetimibe group. Total cholesterol as well as LDL cholesterol was actually reduced in both groups, with the ezetimibe patients showing a greater reduction.
The cardiovascular health parameter of primary interest to the researchers was the thickness of the carotid vessel wall (the area between the very inside lining of the artery, the intima, and the underlying layer where the vessel’s muscle cells reside). The thicker this area, the more constricted the vessel canal (lumen), lessening blood flow. In other words, a healthy artery has minimal wall thickness.
The investigators employed a non-invasive test, an ultrasonogram, to measure the thickness before, during and at the end of the study. Niacin patients had an average reduction of wall thickness of 0.01 mm (millimeters) at eight months, with additional improvement to 0.014 mm reduction at 14 months. The ezetimibe patients showed no decrease in wall thickness. In fact, there was a paradoxical increase in those patients with the greatest ezetimibe-induced decrease in LDL.
No Easy Answer
The cholesterol story is complex. For example, the newly developed drug, ezetimibe, which lowers LDL cholesterol by preventing absorption from the intestines, appears to have additional, less favorable effects on key metabolic pathways.
By comparison, niacin / B-3 is a relatively inexpensive, nonprescription vitamin, shown as early as the mid-1950s to be an effective lipid-lowering agent. It is well tolerated by most people*, although there are two side effects, flushing and itchiness. (These seem to be minimized with an extended-release form.) And according to the recent study referenced here, niacin appears to be a more effective agent, in combination with a statin drug, for maintaining cardiovascular health.
* Metabolized by the liver, as are many drugs, niacin may also cause liver damage.
In a recent issue of the New England Journal of Medicine, a team of scientists and cardiologists published “Extended-Release Niacin or Ezetimibe and Carotid Intima–Media Thickness.” The article describes the group’s experiment with adding a vitamin or a drug to existing statin therapy and how that affected cardiovascular health, especially the condition of the carotid artery.
The patients (208) were divided into two groups. One was asked to take niacin (2,000 mg/day) and the other ezetimibe (a relatively new cholesterol-lowering drug) for a period of 14 months. A number of cardiovascular health-associated parameters were measured just before the study start date, then again at eight months and 14 months after the patients started taking the two test drugs.
The health parameters measured were total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, C-reactive protein, liver-associated enzymes and blood-glucose. The investigators also measured the thickness of the carotid artery wall using a non-invasive technique, ultrasonography.
As a primary end-point, the researchers focused on whether niacin and/or ezetimibe had any effect on the thickness of the carotid artery wall (intima-media thickness). Measurements, at the same intervals as the other health parameters, clearly demonstrated that niacin had a significant positive effect on reducing the arterial wall thickness for better blood flow. The ezetimibe patients either showed no effect or, in some cases, an increase in arterial wall thickness.
Based on these results, along with a lower incidence of major cardiovascular events in the niacin group during the experiment, the investigators concluded that extended-release niacin, when combined with a statin, is an effective therapy (comparatively more so than ezetimibe) for patients suffering from/at high risk for coronary heart disease.
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.
Dr.Treadwell answers your questions.
question: Noticed, in several of the Juvenon Health Journals, that Vitamin D was discussed. Have you seen this month’s release from Mayo Clinic? http://www.eurekalert.org/pub_releases/2009-12/mc-mca120209.php – C
answer: Thank you for the link. Research continues to demonstrate that vitamin D3 plays a role in regulation of cell growth and death, associated with multiple functions in the body. Perhaps among the most important are immune system support and bone metabolism and health.
Recent studies also seem to have changed the thinking on dosage. Initially, 400 IU per day was thought to be sufficient. Now, however, health professionals are recommending that many of us, especially those who reside in the northern zones, should take at least 1000-2000 IU per day.
The vitamin seems to be quite safe, at least up to 2,000 IU per day. It appears that excess amounts are metabolized and excreted. Juvenon is evaluating increasing the amount of D3 in two of our supplement formulas. To review two of the Juvenon Health Journals on vitamin D, click here and here.
Benjamin V. Treadwell, Ph.D., is a former Harvard Medical School associate professor and member of Juvenon’s Scientific Advisory Board.