The UltraMind Solution (80 page)

When your brain cells are injured by overexcitation or die, every one of the problems we have been discussing in this book ensues—ADHD, autism, depression, anxiety, Alzheimer’s, Parkinson’s, and more.

The good news is that we understand how to modulate this system naturally to prevent overexcitation and brain injury.

Many of the things we have found helpful to stabilize mood and an irritable nervous system and to prevent cell death work through their calming action. All slow down the overstimulation of this receptor.

Magnesium is the natural guard against too much stimulation of the NMDA receptor by glutamate, the neurotransmitter that normally flips the “on” switch. Zinc is also a natural relaxant. GABA, taurine, vitamin B
₆
, vitamin D, n-acetylcysteine (the glutathione booster), and even green tea all act as a brake on the overstimulation of the NMDA receptor.

On the other hand, mercury, arachidonic acid (an inflammatory omega-6 fat from dietary sources like meat and dairy), cortisol (the stress hormone), and homocysteine (because of a lack of folate, B
₆
, or B
₁₂
) all overexcite the NMDA receptor, leading to cell death.

Understanding this helps us learn how to prevent overexcitation and calm things down. Doing this is part of the brain-protective and balancing plan in Parts III and IV of
The UltraMind Solution
.

Another one of the key balancing acts you need to keep in mind to protect your mitochondria is your insulin and sugar balance. I am going to explain why in a moment, but before I do . . .

Did you know you can live to be 120 years old by eating as much as you want and drinking lots of red wine?

The only catch is that you have to drink about 1, 500 bottles of wine a day, which would kill you, before you could live forever!

David Sinclair and his group at Harvard found that the red pigment in
grapes called resveratrol could extend life in rats by protecting their mitochondria. He so believes in this compound he started a company (Sirtris Pharmaceuticals, which has been purchased by Glaxo Smith Kline for $720 million) to produce a pharmaceutical derivative of the active compound in red wine, resveratrol.

Though he has discovered something very important, those who view this as the “magic pill” that will allow you to eat whatever you want and live forever are misguided. The body is much more complex than that. But he is onto something drawing the link between resveratrol, aging, and mitochondria, something that affects brain health and has an impact on all chronic diseases.

Let me explain why a magic pill won’t work, and what may really help you live longer and prevent all the diseases of aging, including all brain diseases. He is on the right track, but “magic pills” without more usually don’t work. The focus must be on systems.

News about this new “drug,” resveratrol, says it extends life span, lets you eat whatever you want, and gives you the fitness of a trained athlete without any exercise.

But it is not a drug at all, and the excitement only serves to reinforce the idea that a single molecule (whether it is from a drug or a plant) can solve all our health problems.

Resveratrol comes from grapes (hence the benefit of red wine), peanuts, berries, and a Chinese herb called
hu zhang
(polygonum cuspidate, also known as giant knotweed, which is a common ingredient in many Chinese herbal formulas). A natural plant defense molecule, resveratrol is only one of many beneficial plant compounds called phytonutrients, included in the class called polyphenols, of which there are thousands.

These phytonutrients act in many ways, the most important of which is as a genetic control system, turning on and off genes that help us stay healthy. This is the science of nutrigenomics—or how food is information that tells our bodies what to do, not just a source of calories we need for energy.

If treating people with a simple dose of resveratrol sounds too good to be true, it is.

As much as I support the use of supplements and know about the importance of phytonutrients, all of this excitement about resveratrol is misguided.

Why?

Because looking for a quick fix is misguided. To find the real secret to
longevity, healthy aging, and fitness we need to look at how this compound works and learn from that the lessons we need on how to keep ourselves healthy.

What is the real secret, and how does resveratrol really work?

In one word, mitochondria.

Two recent studies (one of which was done by Sinclair himself) shed light on how resveratrol works, how it impacts oxidative stress, and how mitochondrial function holds the key to health, brain wellness, weight loss, and longevity.

In the first study, published in
Nature
,
²⁰
David Sinclair and his colleagues gave one group of mice a high-fat (60 percent of calories) diet. In middle age these rats all became obese, got diabetes, fatty livers, and died early.

He fed the same diet to another group of mice, but gave them resveratrol at a dose of 24 mg/kg of body weight—which is equivalent to the amount of resveratrol found in about 750 to 1, 500 bottles of wine a day.

That group still got fat, but lived longer and did not get diabetes or heart disease. They were also more agile and had more endurance than the rats that didn’t get the resveratrol. Interestingly, their cholesterol profiles didn’t improve
but
they didn’t get heart disease, showing that cholesterol is not the big evil we think it is.

So how does resveratrol have these effects? And what does this study on rats have to do with brain disease in people?

Let me explain how this relates to your brain. Anything that helps your mitochondria helps your brain, and anything that improves your blood-sugar control, improves insulin resistance and also helps your brain.

How Resveratrol Works

In the study above, resveratrol produced changes associated with longer life span and produced the following biologic effects:

1.
Increased insulin sensitivity leading to better blood-sugar control.

2.
Reduced insulinlike growth factor-1 (IGF-I) levels—a molecule related to a growth hormone that promotes cancer growth.

3.
Increased AMP-activated protein kinase (AMPK)—a signaling system in the body that controls insulin sensitivity and can prevent diabetes.

4.
Increased peroxisome proliferator-activated receptor—coactivator 1 (PGC-1) activity—which is a critical signaling system that turns
on genes that improves blood-sugar control and improves mitochondrial function.

5.
Increased the number of mitochondria produced by the cells— boosting the capacity to turn food into energy and to burn calories.

6.
Improved motor function, making the old rats more agile.

7.
And finally the resveratrol worked by opposing the effects of aging by modifying 144 out of 153 metabolic pathways, controlled by genes, many of which control mitochondrial function.

But what does this study really tell us—that aging, including much of brain aging and disease, is controlled in large part by
sugar
and insulin function in the body! Sound familiar?

Too much sugar in your diet causes your body to produce too much insulin. This triggers more inflammation and oxidative stress leading to mitochondrial injury.
²¹
Mitochondrial damage, in turn, leads to even more insulin resistance. That means anything that protects the mitochondria, like resveratrol, will prevent at least part of the damage that leads to insulin resistance and hence mitigate many possible problems.

People with genetically underperforming mitochondria, like the children of diabetics, are more susceptible to mitochondrial injury if they have a poor diet, don’t exercise, and don’t get enough of the right nutrients to protect their mitochondria.
²²

The next study published in
Cell
by Johan Auwerx,
²³
from the Institute of Genetics and Molecular and Cell Biology in Illkirch, France, tested much higher doses of resveratrol in mice, eighteen times as much, or 400 mg/kg of resveratrol—equal to about 360 capsules of resveratrol for a 130-pound person.

Their findings were even more dramatic. Imagine achieving the fitness of a trained athlete, staying thin, preventing diabetes and heart disease, and living to 120 years of age while eating a high-calorie, high-fat diet (and taking 360 pills a day of resveratrol!).

The rats fed the high doses of the resveratrol along with their high-calorie, high-fat diet had the following effects:

1.
They did
not
gain weight and reduced the size of fat cells.

2.
They didn’t get prediabetes or metabolic syndrome.

3.
They increased the number of energy-producing mitochondria in muscle cells.

4.
It turned up their metabolic thermostat (thermogenesis) and increased fat burning in the mitochondria.

5.
They increased their endurance and aerobic capacity (without exercise).

6.
They maintained their cells’ sensitivity to insulin, hence better blood-sugar control.

7.
They had enhanced muscle strength and reduced muscle fatigue.

8.
They had improved coordination.

9.
There were
no
side effects on any organs.

10.
They increased the activity of PCG-1 alpha, which in turn controls genes that improve the function of mitochondria and blood-sugar control.

This seems incredible. But it is plausible if you understand these two root causes of obesity, brain injury, aging, and disease—blood-sugar control and the health, number, and function of your mitochondria.

That taking
only
resveratrol even at high doses will allow us to live a depraved life of sloth and gluttony and live disease-free forever, is unlikely. But what these studies do tell us is
very
important.

When taken from a systems perspective—understanding
all
the influences on blood-sugar control, insulin, and our mitochondrial function (nutritional balance, hormone balance, inflammation, toxins, energy production, oxidative stress, and psychological stress—or the seven keys to UltraWellness, which lead to an UltraMind)—we can create a lifestyle and program that works to keep us healthy, happy, alert, mentally sharp, thin, and more likely to live to 120.

Finding the Gene Control Switch for Mitochondria

At a conference on longevity and aging I had a chance to have a conversation with Dr. Leonard Guarente from the Massachusetts Institute of Technology, who in 1995 discovered a gene called SIR-2 in yeast that controlled longevity. David Sinclair, who authored one of the studies above, was his student.

The SIRT-1 gene (which is what it is called in humans) or sirtuin family of genes works by protecting and improving the health of your mitochondria.
²⁴
I asked him how this master gene controlled longevity, the gene through which the effects of this grape compound, resveratrol, did its magic.

His answer was quite simple really.
Sugar!
This gene is the master-control switch for healthy aging because it improves blood-sugar balance and insulin sensitivity through its effects on mitochondria.

When your mitochondria are running in top shape, you can metabolize or process all your calories and produce energy. But when they are overloaded with too many empty calories, they are unable to keep up, and too many free radicals are generated, slowing down your cells and your metabolism.

By increasing the activity of this master gene, you improve the overall function of your mitochondria, improve blood-sugar control and insulin sensitivity, and boost your antioxidant defenses. You live longer, and your brain works better.

This is no surprise, since all of the signs of aging such as hardening of the arteries and organ damage (especially brain damage) are increased through worsening blood-sugar control—even before you get diabetes. Diabetics, in fact, have smaller and more poorly functioning mitochondria and get cancer, heart disease, depression, and dementia at far greater rates than the general population.
²⁵

Remarkable new research links mood disorders to problems with insulin and blood-sugar control. In fact, some researchers suggest calling depression “metabolic syndrome type II,” meaning that the changes in the brain from oxidative stress, inflammation, and mitochondrial injury lead to altered mood.
²⁶

So if we could fix our blood-sugar control and boost our mitochondria, we could live longer and disease-free.

Taking a big-picture view, we don’t just want to take a magic pill that will be unlikely to work given all the other real life insults affecting us, such as poor diet, stress, environmental toxins, and sedentary lifestyle.

This just takes us back to the basic principles of systems biology and Functional Medicine at the foundation of
The UltraMind Solution.