08 October 2010

Feeding Your Brain keynote by David Perlmutter

Our keynote presentation at American College of Nutrition conference in New York City was neurologist David Perlmutter, MD. He started off talking to us about the "uniqueness of the human brain."

However, inflammation and oxidative stress ultimately lead to neurological degenerative disease. The brain's antioxidant defenses are limited and inflammation happens in the brain just as anywhere else.

He showed us MRIs of classic brains and those of Alzheimer's patients (along with activated microglia). "This is the picture of what is happening. It is the brain on fire."

In Parkinson's there is an increased density of glial cells expressing inflammatory cytokines, showing oxidative stress and inflammations is related to the disease too.

Typically when Perlmutter helps Parkinson's patients, he tells them the drugs don't treat the disease only the symptoms. "You need to treat the fire," he says.

Now, we also can "unlock the potential of our genes," he says. "It's a fascinating time. We call the study epigenetics and we're learning that we can modulate gene expression."

This is why he is so interested in nutrition: epigenetics. We can modify how our genes express, such as the Nrf2 activation to deal with inflammation and free radical formation.

Activation of transcription factor Nrf2 is powerful, says Perlmutter. It's the "guardian of redox homeostasis," he notes referencing a study.

He says we're going to learn a lot about Nrf2 (along with other factors in epigenetics) in the future, so also finding potential targets for lowering oxidative stress.

"If you're training for a marathon or not sleeping well, these are the pathways that helped protect us. When we were hunter-gatherers and didn't have enough calories, these are the pathways that allowed us to pass on our genes."

He then began talking about curcumin's actions on reducing oxidative stress and protecting the hippocampus in mice, which is key for the protection of the brain against Alzheimer's.

"Curcumin is not only able to lower oxidative stress, but reduce plaque burden [by 43-50%]."

More brain scans were shown, this time of amyloid burden, from a study, and he went back to show that the Indian spice shows "promise for the prevention" of Alzheimer's (Lim et al. J Neuroscience).

The Nrf2 pathway involves a variety of factors including glutathione, inhibiting Nfkappa-B, superoxide dismutase, inhibiting microglial activation, etc.

One of the principal activators of Nrf2 is sulforophane (from broccoli, for example) which is why we always use this as a good detoxifier. He shows an animation about how broccoli creates the activation of Nrf2.

Coffee also is very good for activating the pathway, which is why he showed us an animation of a businessman worshipping coffee (great for oxidative stress).

"Early events in the pathogenesis of Alzheimer's is oxidative stress," he says, so we need to focus on prevention with antioxidants and upregulating antioxidant defense mechanisms.

If you are worried about Alzheimer's because of family history or oxidative stress, then you should consider nutrition to prevent. He says we should also be measuring for oxidative stress early on, especially in Alzheimer's, and be sure people are getting the basics like vitamins A and C.

So many of our diseases seem to be related to toxins too, like Parkinson's (and he shows us an article about pesticides being linked to Parkinson's).

Perlmutter then went on to discuss Brain-Derived Neurotrophic Factor, a neurotropin crucial for integrity of adult neurons and for neurogenesis.

Caloric restriction, exercise, etc., stimulate neurogenesis -- increasing number of neurons -- and he references a study that was the first evidence that diet could influence neurogenesis.

He shows scans of brains on diet restriction where new cells are being formed, which fully differentiate into neurons. What are the factors that can enhance stem-cell therapy in your brain? Calorie restriction.

In humans, there is an upregulation in BNDF with only 25 percent reduction in calories, and diet is a powerful epigenetic factor that could avoid degeneration of the brain into Parkinson's or Alzheimer's.

When we restrict calories, we see produced ketones, reduction of free radicals, and turns on mitochondrial replication. This happens by activation of uncoupling protein so there's less free ATP, less radicals, increased mitochondrial replication, then an increase of ATP and energy.

He shows us images of a mitochondrion and says it's actually involved in controlling DNA (with its own "feminine" DNA). The mitochondria also are involved in whether or not cells live or die.

As a society what are we doing to help people avoid Alzheimer's, which is a devastating disease, and where many of us are at risk.

He puts up a slide that says "upavasa" (some kind of old word about ancient knowledge of brains), then goes back to the modern science. We've come a long way. He shows us pathways again to hone in on the message that by activating specific pathways (through a ketogenic diet) for preventing Alzheimer's.

A ketogenic diet upregulates mitochondrial biogenesis, and so does physical exercise, which augments production of neurogenesis. Exercise also extends the length of dendrites, important in neuroplasticity.

He shows slides on exercise where mice had "dramatic" enhancements in proliferation of neural stem cells.

Then, he talks about how exercise improves mental function in adults at risk for dementia. It's so important.

"Everyone is at risk," he says, since we may have each had our own experiences that put us at risk for dementia.

"If you could create a drug that could do this (enhance cognitive function), it would be the biggest-selling drug of the day," he says, noting that exercise is free for us all to take advantage of now for the plasticity of our brains.

Scientists (Frontiers in Neuroscience, Aug 2010) found that walking increases functional connectivity in the aging brain and attenuating age-related brain disfunction. Physical exercise is a key that is better than any pharmaceutical drug for enhancing Nrf2.

We also know, he says, that eating fish helps people avoid brain degeneration, since DHA normalizes Nrf2. The relative risk of Alzheimer's is reduced by around 70 percent in those that have diets high in DHA (Morris et al, 2003, Arch Neurol).

"If you're going to jump out of an airplane, then you want a wear a parachute," he says. And he tells us we shouldn't completely rely on randomized, controlled trials.

Perlmutter wrote an article previously called "Making New Connections" where he discusses learning about how the brain was able to change, despite prior thinking in medicine.

"New networks are being formed," he says. "The brain is remarkably plastic. It can repair itself." And through these pathways (Nrf2) we can enhance this effect of neurogenesis, neuroplasticity.

He highlights Hebb's law, "Neurons that wire together, fire together."

And he discusses Dr. Merzenich's (author of "Train your mind, Change your Brain") work showing how just mental activity can change the brain.

Plus, Andrew Newberg's work how meditation changes the brain in ways shown on brain scans, which he shows.

Perlmutter studied the anterior cingulate, which allows us to be empathetic, compassionate, socially aware, and intuition. It's strengthened by "spirituality" or any meditative state in which you feel comfortable.

He now discusses our prefrontal cortex and tells us many of us function on a more "primitive level" like fight-or-flight, from the amygdala (the reptilian brain) without thinking things through and becoming much more sympathetic, from the anterior cingulate (empathetic brain).

When we read the newspaper and feel the fight-or-flight, we often think from an "amygdala level." But we can favor the anterior cingulate through meditation, and by engaging in physical exercise, calorie restriction, eating DHA for enhancing Nrf2.

He talks about fasting now: fasting at ramadan, Jesus fasting, other fasting traditions. Fasting is a way to gain access to a higher brain.

He closes with quotes from Einstein, etc, about how through fasting, diet restriction, nutrition, we can become the "beings that we want to become."

After the talk, Dr. Perlmutter received a humanitarian award on behalf of ACN for his work in "Hope for Haiti."

Location:E 103rd St,New York,United States

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