In a relatively new area of science known as epigenetics (which is, at its most basic, the study of changes in gene activity), researchers have found that a protein in the body known as Nrf2 has the power to turn on genes that produce a vast array of antioxidants throughout the body and particularly in the brain. These antioxidants protect our cells from damage caused by free radicals, which are known to cause disease.

Brain cells, in particular, need this protection. The brain is especially vulnerable to damage from free radicals because it uses more energy than other parts of the body and there are more damaging particles there. Free radical damage, including the resulting oxidative stress and inflammation, has been found to underlie general brain aging and many degenerative conditions of the brain, including Alzheimer's, Parkinson's, amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease) and multiple sclerosis.

One of the main Nrf2 researchers is David Perlmutter, MD, a highly regarded integrative neurologist and coauthor of several books, including Power Up Your Brain: The Neuroscience of Enlightenment (Hay House). His recommended brain-health protocol includes nutritional supplements to boost the brain's natural ability to protect itself. Beginning right now, you can start to improve the long-term health of your brain simply by using certain nutrients, many of which may already be familiar to you…

How NRF2 Works

Functioning inside the individual cells of the brain, Nrf2 helps to produce billions of brain-protective antioxidant molecules-far more than you could consume in oral supplements.

One of the brain antioxidants that it produces: Glutathione. Most people don't have enough glutathione in their bodies-especially since glutathione can become depleted because of illness and aging.

As it turns out, glutathione is especially effective at protecting the brain. It destroys free radicals and removes toxins from the brain, and it regenerates other antioxidants, such as vitamin C, which also destroy free radicals.

Glutathione also has been shown to prevent ALS in lab animals, and Italian researchers have reported significant improvements in Parkinson's patients who received intravenous glutathione. Conversely, low levels of glutathione have been linked to increased incidence of Alzheimer's, Parkinson's and ALS in studies with humans.

Maximizing Your NRF2

When patients are treated for these neurodegenerative diseases, they are given drugs that treat the symptoms, not the disease itself. But by activating Nrf2, we can directly tackle the inflammation and oxidative stress that affect the brain.

I have adapted Dr. Perlmutter's protocol for brain health in my own practice. I recommend it for patients who already have neurodegenerative conditions, such as Parkinson's or ALS. I also recommend it for patients with dementia... Alzheimer's...and (starting at about age 40) for those who have a family history of these conditions (two or more family members with either dementia or Alzheimer's) as a way to boost brain health and protect the brain.

I have patients take these supplements based on their conditions. Those with neurodegenerative conditions generally take all of the supplements described below, while those who want to prevent these illnesses can take several of these nutrients.

  • N-acetylcysteine (NAC) and alpha-lipoic acid (ALA). These two natural substances can boost glutathione which, in turn, triggers Nrf2. I recommend that patients take the antioxidants NAC (500 to 1,000 milligrams (mg) daily) and ALA (100 mg to 300 mg daily). ALA can reduce blood glucose, so patients with diabetes need to be monitored.

Other nutrients that activate Nrf2 include the following. Note that you can't get the therapeutic benefit of these nutrients by eating foods containing these nutrients.

  • Docosahexaenoic acid (DHA). More than two-thirds of the dry weight of the human brain is fat, and one-quarter of that fat consists of the omega-3 fatty acid DHA, which is found in fish oil and krill oil. Studies have shown that DHA can help with memory problems.

Not only does DHA dramatically boost Nrf2-related antioxidant activity, it also increases production of brain-derived neurotrophic factor (BDNF). BDNF is a protein that stimulates the growth of new neurons and synapses and helps protect neurons against damage from trauma (such as a bump on the head or temporary lack of oxygen, as in a stroke), environmental toxins and the stress hormone cortisol. Studies have linked low levels of BDNF to increased incidence of Alzheimer's, epilepsy, anorexia nervosa, depression, schizophrenia and obsessive-compulsive disorder.

Dose: 1,000 mg daily. DHA has a blood-thinning effect, so if you take blood-thinning medication, check with your doctor before taking DHA. If you already take an omega-3 supplement, check the amounts of DHA and EPA in your supplement. If you need more DHA to reach 1,000 mg, look for a product that offers DHA only.

  • Curcumin. This nutrient, the active ingredient in the Indian spice turmeric, has a powerful stimulating effect on Nrf2. Like DHA, it also has powerful anti-inflammatory benefits and increases the brain's production of BDNF.

Dose: 200 mg to 400 mg of turmeric extract containing 95% curcuminoids daily.

  • Sulforaphane. The active ingredient in broccoli and one of the most potent activators of Nrf2, sulforaphane is available in supplement form. It stimulates liver enzymes that clear carcinogenic metabolites from the body and brain.

Dose: 200 mg to 500 mg of broccoli seed extract daily.

  • Pterostilbene. This chemical gives blueberries their powerful antioxidant effects. It's chemically related to the more familiar and popular supplement resveratrol but appears to be utilized more readily by the body, and it is especially effective at boosting glutathione production.

Dose: 50 mg to 100 mg daily of pterostilbene. Don't use this supplement if you are allergic to berries.

  • Green tea extract. Antioxidants in green tea improve brain health because they eliminate free radicals. Other compounds in green tea help the body neutralize and eliminate environmental and dietary toxins. This potent antioxidant also works in part by stimulating Nrf2.

Dose: 200 mg to 400 mg daily of green tea extract.

  • Nrf2 Activator. For patients who would rather have the convenience of taking just one supplement instead of the several described above), I recommend Nrf2 Activator. Developed by Dr. Perlmutter, it activates Nrf2 in the body with many of the nutrients listed above, including curcumin, sulforaphane, pterostilbene and green tea extract. The supplement is manufactured by Xymogen, a company for which Dr. Perlmutter is chairman of the medical board of advisers and chief neuroscience officer and in which he has a financial interest). Nrf2 Activator is available only through health professionals. Have your physician contact Xymogen (800-647-6100,

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