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Changing Gene Expression – Powerful Anti-Aging Medicine
The “amplifying” effects of rare and common food constituents on the body’s brain-protection system
8/12/2014By David Perlmutter, MD, FACN, ABIHM
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This article is republished by kind permission of leading brain/nutrition researcher David Perlmutter, MD, FACN, ABIHM, author of the #1 New York Times Bestseller, Grain Brain - The Surprising Truth About Wheat, Carbs, and Sugar – Your Brain’s Silent Killers. We encourage you to explore his website at

Exciting research from the University of Texas Health Science Center has identified what has now been termed the “master regulator of the aging process.”
About Dr. Perlmutter
David Perlmutter, MD, FACN, ABIHM is a Board-Certified Neurologist, Fellow of the American College of Nutrition, and an internationally recognized leader in the field of nutritional influences in neurological disorders.
He’s alerted the public that brain problems including Alzheimer’s disease, other forms of dementia, depression, and ADHD may be prevented with lifestyle and diet changes.
Dr. Perlmutter serves as an Associate Professor at the University of Miami School of Medicine, and is a frequent symposia lecturer at medical institutions as Harvard University, the University of Arizona, Scripps Institute, New York University, and Columbia University.
His many books include: The Better Brain Book, Power Up Your Brain: The Neuroscience of Enlightenment, and the #1 New York Times Bestseller, Grain Brain - The Surprising Truth About Wheat, Carbs, and Sugar – Your Brain’s Silent Killers.
Dr. Perlmutter has also made many TV appearances, including ABC 20/20, CNN, Fox News, The Today Show, Oprah, and the Dr. Oz Show, for which he serves as medical advisor.
“David is an absolute leader in the use of alternative and conventional approaches in the treatment of neurologic disorders. He is on the cutting edge and can help change the way we practice medicine.”
– Mehmet Oz, MD
The process of aging seems to be quite directly correlated with the damaging affects upon our tissues of the actions of chemicals called free radicals (Lewis KN et al. 2010).
We are all familiar with the notion of taking antioxidants to quench free radicals and this has been a focus of scientific research for decades.
And rightfully so. Free radicals are clearly involved in the damage that occurs to our fat, protein, and even our DNA.
Ultimately, although our DNA, our code of life, has repair mechanisms, as we age, the ability of DNA to repair itself, finally fails.
Until quite recently, the main focus of antioxidant therapy has been to supply molecules that inactivate free radicals.
That means, for example, that one molecule of vitamin C, could quench one free radical.
But now leading edge research, like that mentioned above, is focusing on the vast amplification of the body’s own antioxidant systems whereby stimulating DNA can cause the body to actually manufacture vast numbers of protective antioxidant molecules ... far more than anything you could take in a standard antioxidant supplement.
What these researchers and others are focused on is a chemical pathway called Nrf2.
When the Nrf2 pathway is activated, it causes an explosive production of life preserving, anti-aging, protective antioxidants.
The scientists in the research cited above revealed how the Nrf2 pathway is markedly activated in animals with enhanced lifespan.
In fact, one of the key antioxidants amplified by this pathway is glutathione, now known as the brain’s “master antioxidant.”
And beyond just enhancing antioxidant function, activation of the Nrf2 pathway turns off inflammation, while at the same time enhancing detoxification.
The researchers indicated that Nrf2 regulates a diverse array of more than 200 cellular protective genes that neutralize and also detoxify both toxins formed within the body as well as those from environmental exposure.
This science is so profound that it has led to the development of a pharmaceutical agent now FDA approved for the treatment of multiple sclerosis, based on modulating the Nrf2 pathway.
[Editor’s Note: Dr. Perlmutter is referring to the anti-fungal agent called dimethyl fumarate.]
And beyond MS, Nrf2 is now looked upon as a “new therapeutic target in Parkinson’s disease.” (Cuadrado A et al. 2009)
Other areas of research now include amyotrophic lateral sclerosis (Lou Gehrig’s disease), and Alzheimer’s disease as well. But here’s some very good news.
The Nrf2 pathway is readily activated by a variety of natural substances including the spice turmeric, green tea extract, pterostilbene (a form of resveratrol), glucoraphanin (found in broccoli), and even coffee.
[Editor’s Note: Resveratrol is a polyphenol-type antioxidant and anti-fungal agent found in grapes and red wine. The active constituent in turmeric is the synergistic trio of polyphenol compounds called curcumin, which gives turmeric its orange hue and supports immune and brain health in uniquely powerful ways.]
Many of these are readily available as nutritional supplements and can be far more effective at increasing antioxidant production than typical antioxidants.
Truly, we stand at the threshold of a new understanding of how we can change gene expression to enhance antioxidant function, reduce inflammation, and empower our bodies to detoxify.
And how empowering it is to know that this can be accomplished nutritionally.

From the Editor of Vital Choices
We hope you enjoyed Dr. Perlmutter’s essay on protective food factors!
Some critical but little-known facts about the “antioxidants” in plant foods may provide further insight into the subject at hand.
The polyphenol and carotenoid compounds in whole plant foods are commonly called “antioxidants” because they behave that way in test tube experiments.
But in general, these health allies do not exert direct antioxidant effects in the body… at least not to a very substantial extent.
Instead, polyphenols appear to exert strong indirect effects on oxidation and inflammation via so-called “nutrigenomic” effects on gene switches (e.g., transcription factors) in our cells.
Polyphenols’ nutrigenomic effects tend to moderate inflammation and stimulate the body’s own antioxidant network … which includes enzymes, lipoic acid, CoQ10, melatonin, and vitamins C and E.
The richest known food source of polyphenols are raw (non-alkalized / non-“Dutched”) cocoa, berries, plums, prunes, tea, coffee, extra virgin olive oil, beans, and whole grains.
(Highly beneficial procyanidin-type polyphenols abound in cocoa, dark-hued berries – e.g., blackberries, blueberries açaí berries – grapes, red wine, and tea. Comparably beneficial anthocyanin-type polyphenols abound in cherries and most berries.)
Extra virgin olive oil is uniquely rich in hydroxytyrosol, oleuropein, oleocanthal, and other tyrosol esters … a particularly potent class of polyphenols with clinically documented vascular and brain benefits.

  • Cuadrado A, Moreno-Murciano P, Pedraza-Chaverri J. The transcription factor Nrf2 as a new therapeutic target in Parkinson's disease. Expert Opin Ther Targets. 2009 Mar;13(3):319-29. doi: 10.1517/13543780802716501 . Review.
  • Giudice A, Arra C, Turco MC. Review of molecular mechanisms involved in the activation of the Nrf2-ARE signaling pathway by chemopreventive agents. Methods Mol Biol. 2010;647:37-74. doi: 10.1007/978-1-60761-738-9_3. Review.
  • Lewis KN, Mele J, Hayes JD, Buffenstein R. Nrf2, a guardian of healthspan and gatekeeper of species longevity. Integr Comp Biol. 2010 Nov;50(5):829-43. doi: 10.1093/icb/icq034. Epub 2010 May 6.
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  • Sandberg M, Patil J, D'Angelo B, Weber SG, Mallard C. NRF2-regulation in brain health and disease: implication of cerebral inflammation. Neuropharmacology. 2014 Apr;79:298-306. doi: 10.1016/j.neuropharm.2013.11.004. Epub 2013 Nov 19.
  • Sykiotis GP, Bohmann D. Keap1/Nrf2 signaling regulates oxidative stress tolerance and lifespan in Drosophila. Dev Cell. 2008 Jan;14(1):76-85. doi: 10.1016/j.devcel.2007.12.002.
  • Zhang DD. Mechanistic studies of the Nrf2-Keap1 signaling pathway. Drug Metab Rev. 2006;38(4):769-89. Review.
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