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It is Never Too Late to Regenerate Your Brain

A review of Brain Longevity, by Dharma Singh Khalsa, M.D. with Cameron Stauth

June 2001

By Ivy Greenwell

Image with Caption
It is interesting that there is a strong correlation
between IQ and life expectancy. Studies show
that staying mentally active is a mark of the
spectacularly healthy centenarians-it is not
unusual for them to continue to work in their
professional field, or to take up a new hobby
such as painting.

Another fascinating discovery made by Dr. Marian Diamond concerns the effects of a certain kind of pleasure on the limbic system. Namely, Dr. Diamond lavished “tender loving care” upon one group of animals. Not surprisingly, the animals began to show physical signs of better limbic system function. Khalsa thinks that this is associated with “emotional IQ.” But simply being more resistant to stress and sleeping better could mean an overall improvement in brain function. While performing such experiments with children would run into ethical problems, informal observation confirms that children who receive loving care do better not only in school, but in life in general. It is that “upward spiral” of positive input leading to multiple benefits.

What if you had an unhappy childhood? Does it mean you are doomed to poor limbic function and premature brain aging? Not if you deeply understand that “it is never too late to have a happy childhood.” You simply must become a loving parent to yourself, making yourself and your happiness a priority.

For some older individuals, however, pharmacological agents are a must. Khalsa’s favorite “smart drug” is deprenyl, which inhibits the neurotransmitter-degrading enzymes known as MAO-B. Deprenyl is particularly effective at raising dopamine levels. Both deprenyl and another smart drug, Lucidril (centrophenoxine), have been shown to extend the life span of animals (caution: there is wide disagreement about the optimal dosage range of deprenyl for humans. In addition, the dosage that is optimal for short-range benefits may be excessive for long-term usage). Khalsa also often prescribes hydergine, at the standard European dosage of 9 mg a day. Yet another drug he sometimes prescribes is Piracetam, a compound similar to pyroglutamate, a nutrient which stimulates the production of acetylcholine.

In addition, Khalsa favors hormone replacement as a means of raising neurotransmitter levels. He states, “sex hormones influence how efficiently we think, how well we remember, how well we perform physical tasks and how good we feel emotionally” (p. 117). He acknowledges the benefits of estrogens, which include increased acetylcholine production and increased serotonin, as well as improvement in memory through stimulating the growth of new neural connections in the hippocampus. In addition, estrogens lower the production of cortisol (this has recently been found true also of phytoestrogens).

Khalsa does not seem aware of the findings that men on testosterone replacement enjoy improved mental function, both in terms of memory and mood (in the brain, a percentage of testosterone is converted to estradiol, but it is likely that testosterone itself has a range of effects, such as increased dopamine release). He comments only briefly on the benefits of growth hormone replacement, hypothesizing that growth hormone probably stimulates new dendritic growth. In the main, Khalsa appears to favor mainly DHEA and pregnenolone. He believes that in order to achieve optimal mental function, DHEA should be restored to the high levels typical of our late 20’s.

DHEA is indeed a very important neurohormone. It serves as a precursor to other hormones that are necessary for brain function, including estradiol. Although DHEA is our most abundant steroid, it is especially abundant in the nervous system, being 6.5 times more concentrated in the brain than in the serum. Apparently the brain needs the protection that DHEA offers.

Khalsa points out that DHEA levels in the brain are at their highest between the ages of about 25 and 30—the time when memory is also at its peak. Patients with Alzheimer’s disease, on the other hand, tend to have lower DHEA than healthy people of the same age. But unless DHEA is replaced, even healthy people in their 70’s and 80’s typically have only 10% of the DHEA they had in their 20’s.

DHEA is in a constant tug of war with cortisol. High cortisol levels go hand in hand with low DHEA levels. This situation is typical not only of elderly individuals, but also in those who are only middle-aged, but happen to have suffered severe chronic stress. DHEA could be called “the anti-stress hormone.” It protects against glucocorticoid damage. Thus, a deficiency of DHEA exacerbates the damage caused by cortisol.

Dr. Khalsa typically prescribes 50 mg of DHEA per day. Some patients may need only 25 mg; others respond to higher doses, up to 200 mg. He also recommends pregnenolone, another cortisol-lowering and memory-improving hormone, and melatonin, a powerful protector against free radicals. If a patient is hypothyroid, then a thyroid supplement is indicated; low levels of thyroid hormones result in poor mental function and depression.

Because of the time when the book was written, Khalsa does not discuss the effectiveness of SAMe in raising neurotransmitter levels. SAMe’s greatest impact appears to be on the levels of acetylcholine, crucial for memory and learning. Acetylcholine also governs the function of the calming cholinergic pathways that predominate in the parasympathetic system.

DMAE also helps synthesize acetylcholine, but according to Khalsa it should be taken only in the morning, due to its stimulant properties. The point is to keep acetylcholine high all day long. This improves not only cognitive performance during the day, but also helps produce sound sleep at night, since acetylcholine helps screen out stimuli such as random noises that might wake us up.

Vinpocetine enhances cerebral blood flow and increases the production of ATP in the nerve cells, thus “energizing” them. With more energy available, the cells can produce the needed neurotransmitters, defend themselves against free radicals and perform other functions more efficiently. An even more potent neural energizer is acetyl-l-carnitine, which also helps raise the levels of dopamine and acetylcholine, besides acting as an important antioxidant. Acetyl-l-carnitine also improves cell membrane fluidity. In both human and animal studies, acetyl-l-carnitine has been shown to improve memory and learning. However, it is extremely important to remember that acetyl-l-carnitine should be taken together with lipoic acid and other powerful antioxidants such as vitamin E and green tea polyphenols, since increased metabolism also means higher production of free radicals, especially in older individuals.

What about diet and brain rejuvenation? Here we part ways with Dr. Khalsa, since we do not favor a vegetarian diet, particularly one that is heavy on grains. We favor a diet abundant in seafood and vegetables, with grains kept to a minimum, but do agree on the importance of calorie restriction in slowing brain aging. Khalsa suggests that being 20% under the average weight for your height should provide those benefits.

Khalsa is also rather negative about the use of alcohol. He does admit, however, that studies have shown that moderate drinking does appear to preserve cognitive function and lower the risk of Alzheimer’s disease. This may be due to the cardiovascular and stress-lowering benefits of light-to-moderate drinking. But because even a low amount of alcohol is neurotoxic to some degree, Khalsa does have a point: we can obtain the benefits of wine in other ways.

Optimal brain function

First, Dr. Khalsa makes the case for the various B vitamins. For instance, did you know that vitamin B1 (thiamine) was a powerful antioxidant that increases the ability of vitamin E and B6 to protect nerve cells against free radicals? Or that niacin and niacimide have a calming effect, since they potentiate the action of the inhibitory neurotransmitter GABA? B12, B6 and folic acid are indispensable methylating agents, while pantothenic acid (B5) is necessary for the production of acetylcholine.

Image with Caption
Besides being an excellent methyl
donor, choline is of particular
importance for the health of the
nervous system, Khalsa points out.
Choline is a precursor of the key
neurotransmitter acetylcholine,
which is crucial for memory and
sleep maintenance.

As previously mentioned, this book was published before the benefits of SAMe became better known. Those who find SAMe too expensive can turn to the common and very affordable methylating agents such as B12, B6, folic acid, trimethylglycine (TMG) and choline. We are only now discovering the anti-aging importance of maintaining youthful methylation, one of which is the lowering of homocysteine levels. Basically, Alzheimer’s disease and atherosclerosis are closely related; Alzheimer’s patients have elevated homocysteine levels. Likewise, older people with high homocysteine tend to perform poorly on some cognitive tests. And yet a few inexpensive vitamins can be very effective in lowering the levels of this harmful substance.

Besides being an excellent methyl donor, choline is of particular importance for the health of the nervous system, Khalsa points out. Choline is a precursor of the key neurotransmitter acetylcholine, which is crucial for memory and sleep maintenance. Choline also maintains “brain plasticity,” meaning the ability to form new neural pathways if the old ones are destroyed. It helps protect and restore communication between nerve cells by protecting dendrites, the tiny branch-like parts of neurons that reach out to other neurons. Patients with memory loss may experience a significant improvement simply by supplementing with choline.

Vitamins A, C and E are indispensable allies in the struggle against brain aging. Selenium and zinc also function as antioxidants; in addition, zinc plays a role in maintaining healthy cell membranes and helps detoxify the brain of lead.

Though Dr. Khalsa does mention the amino acid taurine as an effective antioxidant, we think its neuroprotective function should be given more emphasis. Like GABA, taurine appears to have a calming, inhibitory effect. Taurine may be of great value in preventing excitotoxic damage, as well as epileptic seizures. In addition, the cardiovascular benefits of taurine (it lowers blood pressure, for instance, and decreases insulin resistance by acting as an insulin mimetic) also imply benefits for the brain. As Khalsa points out, “what is good for the heart is good for the brain.” Altogether, when one also considers taurine’s role in helping prevent macular degeneration, this is a neglected nutrient that needs to be widely publicized. It’s interesting that taurine is a unique amino acid in that it is not used for building proteins; the body uses it for many other purposes, such as neurotransmission.

Among other amino acids, Khalsa stresses the benefits of glutamine, methionine and arginine. Glutamine supplementation has been shown to raise the levels of two important neurotransmitters, the excitatory glutamate and the calming GABA; the brain decides which neurotransmitter is needed more at any given time. Methionine, a sulfur-containing amino acid, is not only a precursor of SAMe, but also an antioxidant. It can also chelate heavy metals such as mercury or cadmium (caution: unless you are a strict vegetarian, you are probably getting plenty of methionine from the diet; excess methionine can be harmful). Arginine has many functions, one of which is to serve as a building block for a polyamine called spermine, important in memory formation.

Since the balance of neurotransmitters is essential, it would be unwise to try to raise only dopamine, or only acetylcholine. Serotonin also decreases with age. Hormone replacement is one important way to sustain more youthful serotonin levels and serotonin receptors. In addition, the amino acid tryptophan acts as a precursor for serotonin production. It is best to obtain it from the diet.

Magnesium likewise has a calming effect. People with type-A personality are likely to show more magnesium excretion, and thus become deficient in magnesium. In addition, magnesium increases cell membrane fluidity, thus enhancing the neurons’ ability to receive nutrients. Magnesium is very important for the brain also because it is a natural calcium antagonist, and thus helps protect against the damaging (often deadly) buildup of calcium ions (excitotoxicity). It has been found that the brains of Alzheimer’s patients show a deficiency of magnesium and toxic levels of calcium.

Siberian ginseng is Khalsa’s favorite tonic. Ginseng has an interesting property of lowering the release of cortisol by stimulating the production of adrenaline (epinephrine). When the supply of adrenaline is plentiful, less cortisol is released in response to stress. Adrenaline is the preferred stress chemical because it is quickly cleared out of the body, and its effects are less harmful. It also boosts reaction time and cognitive function. By increasing adrenaline at the expense of cortisol, ginseng has been found to help protect against stress-related diseases.

Ginkgo biloba is one of the stars of neuroprotection. No brain longevity program would be complete without ginkgo. The ginkgo tree survived even being ground zero in Hiroshima. Known to live as long as a thousand years, ginkgo is itself a metaphor for longevity. It is also the oldest “smart drug.” Various preparations of ginkgo have been used in Chinese medicine for 5,000 years. The potency of ginkgo’s active compounds deserves a much closer study, since besides being a brain tonic, ginkgo also shows a strong promise of being able to extend life span.

At this point ginkgo is famous chiefly for its ability to increase “brain power.” Khalsa reports that in one study of patients with memory loss, a single 600 mg dose of ginkgo caused a significant improvement in short-term memory within one hour of ingestion (lower doses such as 240 mg did not produce this immediate and dramatic response). 600 mg also happens to be the dose that was shown to improve alertness and learning even in healthy young people.

How does ginkgo work? We know that it improves cerebral blood flow and peripheral blood flow, which means that more oxygen and nutrients can be delivered to the cells. It lowers blood pressure and dilates peripheral blood vessels. It decreases the levels of the platelet-activating factor (PAF), a chemical which impedes blood flow by causing platelet aggregation. In popular parlance, ginkgo makes the blood less “sticky.” Hence the benefits of ginkgo for migraine sufferers. The enhancement of microcirculation in the eyes may be the chief explanation for ginkgo’s ability to slow the progression of macular degeneration and other retinal damage. Ginkgo is also an effective treatment for tinnitus (“ringing in the ears”) and vertigo. It is also under investigation as a treatment for asthma. In addition, men seeking an improvement in erectile function have found that ginkgo’s vascular benefits are not confined to the brain.

In addition, the active compounds in ginkgo (various flavonoids such as quercetin and terpene lactones) act as very strong antioxidants, improve membrane fluidity and inhibit glucocorticoid synthesis (this has also been found true of other bioflavonoids as well as of human estrogens). Ginkgo has been found to blunt the response to stress, and to help prevent the age-related or stress-induced loss of a certain type of serotonin receptors that happens to be involved in learning and memory. All in all, it is not surprising that a recent study found that ginkgo not only preserves cognitive function in rats, but also extends their life span.

Image with Caption
"Brain longevity programs are
much more than just programs
designed to enhance the
longevity of the brain; they are
also body longevity programs.
The mind and body are one."

An interesting and somewhat unusual recommendation is “green drinks.” These are the powdered preparations of cereal grasses such as young barley or wheat grass, sometimes with addition of chlorella. Khalsa states that apart from chlorophyll and various minerals and vitamins, the peptides (protein fragments) contained in green drinks provide a ready substrate for the production of neuropeptides such as the well-known beta-endorphins. Those who try green drinks usually swear by them, since the energizing and antioxidant effects (better skin, clearer whites of the eyes, more energy, arthritis relief) can be seen within a short time. If the only piece of advice you follow is to start drinking green drinks, this alone can do a lot for you. Combined with ginkgo and other supplements, green drinks are the rocket boosters of rejuvenation.

We find it somewhat disappointing that Dr. Khalsa does not recommend fish oil and/or frequent consumption of fish. At this point there is little doubt about the enormous value of fish and fish oil for cardiovascular and neural health. Recent findings also show that omega-3 fats are potent antidepressants. In fact, they are now thought to have certain chemical similarities to lithium, and have been found effective even in bipolar disorders (the manic-depressive mood disorders). Thus, fish could be called “mood food” as well as “brain food.” In our view, anyone who is serious about preventing Alzheimer’s disease (or even depression) can’t afford to neglect fish oil.


This book is extraordinary in its richness. Also extraordinary is the loving, caring tone, which itself is therapeutic. The central message is simple and hopeful: we can preserve most of our youthful cognitive function by lowering our cortisol level. In addition, we can achieve further enhancement by nourishing the brain with pleasure, both physical and mental exercise, and the right diet and nutrients. Once such enhancement is achieved and optimal neurochemistry prevails, we can discover our real self—ourselves at our best, with the brain operating at its full power. “That self has been beaten and bruised by stress, exhaustion, neurological toxins and your own fear and anger,” Khalsa states (p. 83). Nevertheless, that “optimal” self can be recovered; the stress-free “magical mind” can reveal its riches not only in childhood, but also in late adulthood.

Far from being dryly scientific, Khalsa doesn’t hesitate to share with readers some life wisdom. Much stress—and consequently premature brain aging—is due to various self-destructive beliefs and attitudes. Khalsa counsels making happiness, not money, your top priority. “If you give up on happiness, you give up on life,” he states. “Happiness—or joy, or hope, or contentment—is the wellspring of all energy, and the primary vitalizing force of life” (p. 289).

Dr. Khalsa emphasizes that rather than being passive victims of the lethal downward spiral, we can activate the upward regenerative spiral. And by rejuvenating the brain, we also rejuvenate the whole body: “Brain longevity programs are much more than just programs designed to enhance the longevity of the brain; they are also body longevity programs. The mind and body are one.” Khalsa asserts again and again that if we take good care of the brain by following a brain longevity program, we can stop degeneration and achieve regeneration. As proof, he cites his clinical experience with numerous patients of all ages.

To quote Dr. Khalsa as he concludes the book: “You’ve learned that aging isn’t always a process of degeneration, but can be an opportunity for regeneration. You’ve learned that if you nurture your brain, you can be intelligent and happy during every stage of your life. You’ve learned that controlling your stress can make you smarter—now, and forevermore. Don’t give up. The best is yet to come. Your life, as always, lies ahead.”

—Ivy Greenwell