Medicine For People!

April 2006: Brain Health as We Age: Part Three – The Little Engines That Could

  • Part Three – The Little Engines That Could
    • Quick Review
    • Alzheimer's and Parkinson's
    • Free Radicals Are the Problem
    • Mitochondrial Nutrition
      • Acetyl-L-carnitine
      • Alpha-lipoic acid
      • Coenzyme Q 10
    • An Ounce of Prevention
    • The Bottom Line

Welcome to the third in a series of articles about the brain and how to keep it healthy as we age. This month, after a quick review of previous articles, I will explain one of the ways that the brain can lose function. I'll use Alzheimer's and Parkinson's disease as examples. After that, we'll discuss three nutrients that should prevent or mitigate damage due to normal aging as well as more serious disease. Prevention is the key. Once brain degeneration has occurred, it's difficult to repair it. Let's look now at what you can do to maximize your chances of keeping a healthy, happy brain.

Some of this material is pretty technical, but I hope you'll stick with it. There is much conflicting information out there; many writers select only those facts that support the point of view they want to advance. I have sifted through a good deal of research to give you all sides of the story. By knowing what we present here, you'll be better able to make informed decisions about how to keep your noggin at full horsepower.

Quick Review

In the first article of this series we described the brain as a complex structure with billions of tiny fibers and trillions of connections, all surrounded by delicate membranes that require constant energy input just to keep from falling apart. Every living cell requires unending energy to maintain order in a thousand ways. From every square millimeter of surface area, the cell needs to pump out calcium, which, if not eliminated, will kill the cell.

In our second article we explained that because brain fibers have so much surface area, they are more prone to oxidation and thus require much more energy than any other tissue. At three pounds weight, the brain consumes about a fifth of the twenty-five watts of power we require for bodily function. That's eight watts per pound, compared to about half a watt for every other kind of tissue. We showed that the energy for this process comes from tiny structures in the cell called mitochondria. These carry their own DNA, which is ten times more susceptible to oxidative damage than the DNA in the nucleus of the cell. When these mitochondria run down, they are no longer able to maintain cellular function. Even in normal people, neurons fail as we age. They fail even faster in people with Alzheimer's disease and other neurodegenerative disorders such as Parkinson's disease.

Brain Failure with Alzheimer's and Parkinson's

I hope neither you nor a loved one gets Alzheimer's or Parkinson's disease. Still, learning what happens to the brain in these conditions will help you understand more about the normal brain aging we all have to contend with.


The top image shows a normal brain, facing left. The brain tissue occupies most of the space available inside the skull. The creases separating the cortical gyri (those sausage-like outer layers of the brain) are narrow, except for one crease running from lower left toward the middle of the image. That separates the temporal lobe from the rest of the brain. The brain below shows the changes with Alzheimer's disease. The cortical gyri have atrophied. Were you to look under a microscope, you'd see a dearth of grey cells. Were you to weigh the brain, it would be significantly lighter.

Now let's look at the brain of someone with Parkinson's disease.


The lower-left image shows a normal brain. The brain fills the entire cranial cavity. The midbrain is highlighted in brown; that area is enlarged at the upper right. The darkest part is the substantia nigra, an area rich is melanin, the same pigment that darkens our skin. Oxidant stress, either from normal living or from toxins such as pesticides and heavy metals, destroys the cells of the substantia nigra, as seen in the lower right image. This results in the initial physical symptoms of Parkinson's disease, such as tremor.

Unfortunately, 70 percent of people with Parkinson's disease will lose cognitive ability as time goes on.

In people with familial Parkinson's disease, two of the four genes involved are mitochondrial genes. Faults in these genes prevent the mitochondria from functioning at full capacity.

Free Radicals Are the Problem

A young and robust mitochondrion, be it in the substantia nigra or the belly button, uses about 95 percent of the oxygen it processes to burn its fuel. About 5 percent of the oxygen escapes the process and generates free radicals. Free radicals, molecules with unpaired electrons, are the loose cannons of the biologic world. Our body is prepared for the attack of the free radicals with an artillery of anti-oxidants, including glutathione, vitamin E, superoxide dismutase, and alpha-lipoic acid.  These antioxidants enter the fatty milieu inside the mitochondrion; vitamin C does not. We make different antioxidants for different purposes.  In both Alzheimer's disease and Parkinson's disease, levels of these intracellular antioxidants are diminished. They are especially scarce in the substantia nigra in Parkinson's disease and in the frontal cortex in Alzheimer's disease.

Current medical thought is that Alzheimer's disease is the net outcome of many factors that influence the brain. These include genetic predisposition and lifestyle factors. For Parkinson's disease, mitochondrial weakness is the primary factor in the initiation of the illness.

Both conditions, whatever initiates them, involve failure of the mitochondria. Both show improvement when mitochondrial nutrients are provided.

Mitochondrial Nutrition


Our bodies make L-carnitine and use it to move fuel into our mitochondria. Mitochondria are 'picky eaters.' They'll eat just two things, pyruvate and fatty acids. (We make pyruvate from carbohydrates, and we'll talk about it when we get to another nutrient, alpha-lipoic acid.) For now, let's concentrate on fatty acids. These are the kinds of fat you find in bacon or your spare tire. On their own, fatty acids can't get into the furnace of the mitochondria to be burned. They need help, and that help is a substance called L-carnitine. Even though we make and recycle our own L-carnitine, levels fall as we become older.

The Blood-Brain Barrier

Carnitine is readily available as a supplement but does not improve brain function. Why is that? The brain is unique among the organs in that it sequesters itself behind a barrier, the blood-brain barrier. The blood-brain barrier inhibits bacteria, viruses, fungi, and the white blood cells that fight them from entering the brain tissue [Link to Blood Brain Barrier in Brain Aging Details.doc]


This illustration shows a capillary in the brain. The blood-brain barrier is the especially tight lining of this blood vessel, the blue balls are the various substances in the blood stream, and the green objects symbolize the mechanisms in the capillary lining which separate those substances which will be admitted into the brain from those which must be kept out. Only certain kinds of substances, or drugs for that matter, will pass this barrier.

L-carnitine does not cross the blood-brain barrier. For those of you who are interested in chemistry, I'll show you a picture of its molecule.

Now let's add a couple of carbon atoms, an oxygen, and a couple of hydrogen atoms; this arrangement the chemists call an acetyl group. You get acetyl-L-carnitine.

That little tail below the molecule, the acetyl group, enables the molecule to cross the blood-brain barrier and enter the brain. The acetyl group benefits the brain in other ways, as well.

The main benefit of acetyl-L-carnitine is that it provides the L-carnitine that the little engines that could, the mitochondria, need to access to their fatty acid fuel. Then they can pump out calcium and preserve the structure and function of the brain tissue. There are many, many clinical studies on the affects of acetyl-L-carnitine on the brain.

Too often, we make a diagnosis of Alzheimer's disease when a person has lost the majority of his or her cognitive ability. It just doesn't take that much brain power to be pleasant, get along with others, and maintain some semblance of normality. Once impairment is obvious, damage is severe. At that time your major hope is that the dementia is from hypothyroidism, depression, drugs, vitamin deficiency, or something else more treatable than Alzheimer's disease. Because it improves the function of the mitochondria that keep your neurons alive and kicking, acetyl-L-carnitine is a very useful way to prevent dementia in the first place.

Alpha-lipoic Acid

Another important nutrient is alpha-lipoic acid, a powerful anti-oxidant. The beauty of alpha-lipoic acid is that it penetrates the blood-brain barrier with ease.

This is what alpha-lipoic acid looks like after quenching two free radicals.

In this state it can quench one more and go on to be recycled for further use. Whenever an antioxidant grabs a free radical, it has to be recycled or replaced. Alpha-lipoic acid is able to help other important antioxidants like vitamin E, glutathione or vitamin C refresh themselves.

Alpha-lipoic acid has two other very important functions.

  1. Alpha-lipoic acid complements acetyl-L-carnitine by bringing in pyruvate, the final form of carbohydrate, the other fuel for a mitochondrion.
  2. Two mitochondrial energy production processes absolutely require the presence of alpha-lipoic acid. That means, no alpha-lipoic acid, no energy production.

Both acetyl-L-carnitine and alpha-lipoic acid help mitochondria engage in an "upward spiral." They give the mitochondria enough fuel to ramp up energy production and protect them from oxidative damage and damage from calcium.

In a group of people who have progressed to the point of Alzheimer's disease, a small trial of alpha-lipoic acid at 600 mg per day for one year did slow progression. However, "slowing progression" is a discouraging target. I believe these nutrients are more useful when used long term for prevention.

Coenzyme Q 10

Here is a picture of Coenzyme Q10.

Coenzyme Q10 is absolutely required for mitochondrial energy production. Unfortunately, aging mitochondria run short of this substance.

Doctors at the University of California at San Diego gave coenzyme Q10 or a placebo to patients with Parkinson's disease. Improvement in mood, motor skills, and cognition occurred in the group given 1200 mg coenzyme Q10 per day. Those given lower doses had little or no improvement. More information on CoQ10.

Vitamin E

To be complete, let me mention one final major dietary antioxidant, vitamin E. Vitamin E acts within the cell membranes to reduce oxidation of the membrane. I think time will show us that it protects us from Alzheimer's and related diseases. So far studies have shown benefit only from vitamin E in the diet, not from supplements. However, the most necessary form of vitamin E, gamma-tocopherol, hasn't been used in these studies. The alpha-tocopherol used instead actually displaces gamma-tocopherol, and so may be worse than useless.

An Ounce of Prevention

Alpha-lipoic acid, acetyl-L-carnitine, and coenzyme Q10 have proven (but too often unspectacular) benefit for those with Parkinson's disease and Alzheimer's as well for people with other neurodegenerative diseases such as multiple sclerosis, stroke, Huntington's disease, and amyotrophic lateral sclerosis.

So we don't want to wait until these conditions are established. We know that an early occurrence – if not a first step – in many neurodegenerative diseases including dementia is a failure of the mitochondria. Once mitochondria begin to fail, the water starts filling the boat. The calcium starts entering the cell. It isn't too surprising that once the boat is almost full of water, repairing the pump doesn't work. If we want the boat to float as long as possible, the pump (those pesky mitochondria) is a major place we need to put our attention.

The Bottom Line

In this newsletter we've reviewed three important nutrients that slow brain aging. These nutrients are not cheap. A month's supply of additive-free alpha-lipoic acid at 600 mg per day costs about $37 at our clinic. Acetyl-L-carnitine from a vendor who passes independent quality assessment from, but who has some additives in the capsule, costs $48 per month at 2000 milligrams per day. (One additive, magnesium stearate, may bind to the active ingredient, reducing absorption, and can cause stomach upset in people who take many capsules a day. However, it greatly reduces the production cost of each capsule. We'll talk more about this a few months from now.)

In later newsletters, I will address other factors, besides mitochondrial failure, that cause aging of our brain. You'll learn that there are some things you can do that are almost free. Please wait until you have the entire story before deciding what to do for prevention. Whatever you do, you want to do it for the long haul. That is why it I am going into so much detail in this series of articles. I want to equip you to make a rational plan that makes medical and economic sense and doesn't result in another half-empty bottle of capsules in the back of the kitchen cabinet.

CJK May 24, 2006



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Medicine for People! is published by Douwe Rienstra, MD at Port Townsend, Washington.