Durk Pearson & Sandy Shaw’s®
Life Extension NewsTM
Volume 14 No. 2 • April 2011


A readers’ survey by Nature1 showed that one in five respondents already used some form of cognition-enhancing drug.
1. Maher, Nature 452:674-675 (2008).

The following quote helps explain why the United States federal government was designed as a government of limited powers (unlike a democracy, where the only limit is that a 50+% majority of the vote overrules the minority) and why there is NO mention of democracy in the Constitution:

[D]emocracies have ever been spectacles of turbulence and contention; have ever been found incompatible with personal security, or the rights of property; and have, in general, been as short in their lives as they have been violent in their deaths.
— James Madison,
Federalist No. 10, 1787

If, from the more wretched parts of the old world, we look at those which are in an advanced stage of improvement, we still find the greedy hand of government thrusting itself into every corner and crevice of industry, and grasping the spoil of the multitude. Invention is continually exercised, to furnish new pretenses for revenues and taxation. It watches prosperity as its prey and permits none to escape without tribute.
— Thomas Paine, Rights of Man, 1791

I believe that banking institutions are more dangerous to our liberties than standing armies. If the American people ever allow private banks to control the issue of their currency, first by inflation, then by deflation, the banks and corporations that will grow up around the banks will deprive the people of all property—until their children wake-up homeless on the continent their fathers conquered.
— Thomas Jefferson, 1802

Only those who will risk going too far can possibly find out how far one can go.
— T. S. Eliot

Natural disasters and man-made tragedies have always been a feature of life on Earth …
— Start of an editorial in the 14 Apr. 2011 Nature
(D&S Comment: Huh? These people seem to be getting farther and farther from reality.)

Niacin is even more effective than previously thought

Niacin Inhibits the Progression of Atherosclerosis
New Mechanisms Help Explain Its Protective Effects

Niacin is the most efficacious HDL cholesterol-elevating drug used in clinical practice. However, the mechanism by which niacin achieves that effect is still unknown. In a new paper,1 scientists report that in a mouse model of atherosclerosis, niacin inhibited the progression of the disease even though under the conditions of their experiment total cholesterol and HDL cholesterol plasma levels were unaffected.1

It has recently been discovered that niacin activates a receptor called GPR109A (its primary endogenous ligand—that is, its physiological activator—is not known, but the receptor is also activated by butyrate, formed in the colon by fermentation of fiber by gut microbes). When bone marrow was transplanted from mice lacking GPR109A into atherosclerosis-prone mice (whose own bone marrow had been destroyed by irradiation), the protective effect of niacin against atherosclerosis was eliminated,1 suggesting that immune system cells derived from the bone marrow are involved in the protective effects of niacin via GPR109A.

The researchers used male LDL-R deficient mice (mice deficient in the receptor for LDL) that were kept on a high fat diet (containing 1.5% cholesterol) to promote the development of atherosclerotic lesions. Of those mice, the ones that received 0.3% nicotinic acid (niacin) had a reduction of about 25% of atherosclerotic lesions in all regions of the aorta. However, in mice on the high fat diet lacking both the LDL receptor as well as GPR109A, the receptor for niacin, niacin provided no protection against atherosclerotic lesions—they were indistinguishable from the mice lacking both the LDL receptor and the GPR109A receptor and receiving no niacin. Hence, the niacin receptor was critically involved in the anti-atherosclerotic effect of niacin. As noted above, the beneficial effects of niacin in these genetically engineered mice were not accompanied by reduced LDL cholesterol levels, unlike in humans; in the two weeks of niacin treatment, only triglyceride levels showed a small reduction, by 11%–18.5%. “Thus GPR109A-dependent anti-atherosclerotic effects of nicotinic acid were not accompanied by any changes in cholesterol or HDL cholesterol plasma concentrations.”1

The researchers also discovered that macrophages, bone marrow derived immune cells that are important in the development of atherosclerotic plaques, express GPR109A. Macrophages that infiltrate atherosclerotic plaques carry fats such as oxidized LDL into the arterial intima where the macrophages then develop into foam cells. In this study, the authors found reduced recruitment of macrophages into atherosclerotic plaques by 75% under niacin treatment. Moreover, they found that niacin, via GPR109A, can change the differentiation state of macrophages, both in vitro and in vivo, inhibiting the development of the pro-inflammatory (M1) form of macrophages. Niacin also increased the expression of ABCG1, an important cholesterol transporter that promotes cellular cholesterol efflux, in macrophages from wild type but not GPR109A-deficient mice.

Interestingly, niacin also decreased the expression of MCP-1, an inflammatory mediator, in plaque macrophages exposed to IFN-gamma (interferon gamma).1 The authors cite other papers2,3 that recently showed that niacin suppressed expression of various inflammatory mediators, including MCP-1, in adipocytes (fat cells, which also express GPR109A) and increasing the expression of adiponectin, an important anti-inflammatory molecule released by fat cells.

Neutrophils are other bone-marrow derived cells that also promote the development of atherosclerotic plaques. The researchers® did not specifically examine the effects of neutrophils in this study, but note that they cannot exclude the possibility that neutrophils (which also express GPR109A) may have been involved in the anti-atherosclerotic effects of niacin seen in this study. They note that, importantly, niacin exerts a pro-apoptotic effect on neutrophils under in vitro conditions, as reported in a separate study by others.4 This could be of considerable importance in the many diseases in which prolonged activation of neutrophils delays the resolution of inflammation, resulting in chronic inflammatory diseases, such as COPD.

The authors conclude: “We conclude therefore that GPR109A mediates anti-inflammatory effects, which may be useful for treating atherosclerosis and other diseases.”

Another paper5 presents evidence that a variety of plant phenolic acids also suppress adipocyte (fat cell) lipolysis (release of fatty acids) via activation of the nicotinic acid receptor GPR109A. The authors explain that “both phenolic acids and nicotinic acid are small carboxylic acids with close structural similarity.” They also point out that “certain phenolic acids, such as benzoic acid, also induce a flushing response and prostaglandin D2 release in a manner similar to that of nicotinic acid treatment.” For example, they identified strong phenolic inhibitors of adipocyte lipolysis: as compared to nicotinic acid with an IC50 (μM) [amount needed to inhibit lipolysis by 50%] of 0.2μM, caffeic acid had an IC50 of 14 μM and gallic acid had an IC50 of 30 μM; both caffeic acid and gallic acid bound GPR109A but were far less potent binders than nicotinic acid.5

These new data add considerably to our reasons for taking niacin regularly. The two of us take 3 capsules of our niacin formulation capsules (200 mg of niacin per capsule) four times a day and have been doing so for over 25 years. Yes, we do experience flushing. Fortunately, neither of us find it troublesome. We know that the flushing is a major reason that many people won’t take more than a pellagra-preventing dose of niacin, which is not enough to provide the above effects. Taking niacin with food can help reduce the effect of flushing. However, we do not recommend time-release niacin, which has been found in a small percentage of people to have liver toxicity effects. Durk’s LDL and VLDL cholesterol and triglycerides run high (hypercholesterolemia and hyperlipidemia are familial traits) if he does not take niacin regularly.

Also, it is important to note that if you plan to take more than about 800 mg of niacin a day, you should have your liver tested periodically to ensure that your liver has no problem with high-dose niacin. The liver tests used to detect potential toxicity from high dose niacin are the same as those used to check for liver toxicity in people taking statins and, interestingly, the likelihood of experiencing liver toxicity is much higher in those taking statins as compared to niacin. Moreover, the muscle damage (rhabdomyolysis, a serious condition which can even be life-threatening) that occurs in a small fraction of those taking statins does not occur with niacin supplementation.

References

  1. Lukasova et al. Nicotinic acid inhibits progression of atherosclerosis in mice through its receptor GPR109A expressed by immune cells. J Clin Invest 121(3):1163-73 (2011).
  2. Digby et al. Anti-inflammatory effects of nicotinic acid in adipocytes demonstrated by suppression of fractalkine, RANTES, and MCP-1 and upregulation of adiponectin. Atherosclerosis 209(1):89-95 (2010).
  3. Plaisance, Lukasova, et al. Niacin stimulates adiponectin secretion through the GPR109A receptor. Am J Physiol Endocrinol METAB. 296(3):E549-58 (2009).
  4. Kostylina et al. Neutrophil apoptosis mediated by nicotinic acid receptors (GPR109A). Cell Death Differ 15(1):134-42 (2008).
  5. Ren et al. Phenolic acids suppress adipocyte lipolysis via activation of the nicotinic acid receptor GPR109A (HM74a/PUMA- G). J Lipid Res 50:908-14 (2009).

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