The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 18 No. 5 • September 2015


Decreased Methylation > Increased Inflammation?

Protection Against Decreased Methylation by Betaine

It has been reported in recent papers that there is an average decrease in methylation levels in the regulation of genetic expression, an epigenetic change that has become a very hot area of research in aging and in the occurrence of a large variety of inflammatory and other diseases. Average decrease in methylation means just that, most genetic methylation decreases but there are some areas, such as the expression of some tumor suppressors that are overmethylated and, hence, less expressed, increasing the risk of cancer.

A very new paper (Veldhoven, 2015) reports that an epigenome-wide association study found there was an average decrease in methylation levels years before breast cancer was diagnosed. The authors suggest that this is a good biomarker for very early detection of possible breast cancer.


  • van Veldhoven, Polidoro, Baglietto, et al. Epigenome-wide association study reveals decreased average methylation levels years before breast cancer diagnosis. Clin Epigenetics. 7:67 (2015).

PGE2, a powerful inflammatory prostaglandin (discussed extensively in my paper (Part I) on the cause of the niacin flush—see at, “Why the Niacin Flush May Be Surprisingly Beneficial to Your Health” in the August 2015 issue—may be involved here. Importantly involved in inflammatory diseases, PGE2 has recently been reported (Venza, 2012) to induce interleukin-8 derepression (restores IL-8 expression from tight regulatory suppression) in human brain astrocytoma cells, where the increased IL-8 expression recruits and activates immune and inflammatory factors, increasing the spreading and invasiveness of the deadly glioma brain tumor.

The paper (Venza, 2012) reported that the PGE2 induced derepression of PGE2 took place through coordinated DNA demethylation and histone hyperacetylation. Interestingly, there are some other inflammatory diseases, such as COPD (chronic occlusive pulmonary disorder) where histone deacetylation is decreased (that is, there is hyperacetylation of the histone) at HDAC-2, histone deacetylase 2. (NOTE: Importantly, some diseases are associated with increased levels of histone deacetylases and others with increased levels.) In the second part of my paper on how the niacin flush may benefit your health there is a section at the very end of natural substances that, like the niacin flush, reduce the activity of PGE2. That includes substances such as omega-3 fatty acids, curcumin (constituent of turmeric root), and ginger, for example.


  • Venza I1, Visalli M, Fortunato, et al. PGE2 induces interleukin-8 derepression in human astrocytoma through coordinated DNA demethylatiuon and histone hyperacetylation. Epigenetics. 7:11, 1315-30 (2012).

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