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Enhancing Cognitive Function

Keeping your memory in tip top shape

May 2000

By Ivy Greenwell

"Viagra" for the brain

First introduced 22 years ago in Hungary for the treatment of vascular dementia-a disorder resulting from insufficient blood flow to the brain tissue-vinpocetine has gradually gained popularity as a European "smart drug." Recently it has become available in the United States. It is a promising neuroprotective supplement and cognitive booster.

It is interesting that vinpocetine has a similar mechanism of action as Viagra. Both are known to be effective phosphodiesterase inhibitors. That is, they work to enhance blood flow by inhibiting an enzyme in the phosphodiesterase family. Not surprisingly, the main benefit of vinpocetine is an improvement in cerebral blood flow. More blood reaching the brain cells means better oxygenation, nutrition and waste removal-all of which adds up to more youthful brain function.

Vinpocetine has also been found to improve the transport of glucose (both uptake and release) across the blood-brain barrier. Low cellular energy production is perhaps the primary factor underlying all aging-related brain degeneration. In addition, vinpocetine has been shown to increase the firing rate of certain types of noradrenergic neurons, which could explain one mechanism of its action as a cognitive booster.

The enhancement of blood flow and energy production means that vinpocetine is particularly recommended for people whose cognitive dysfunction stems chiefly from insufficient blood flow to the brain. Vinpocetine also shows promise in helping prevent damage to vision, especially dry macular degeneration. Vinpocetine likewise appears to improve blood flow to the inner ear, thus protecting hearing. Interestingly, vinpocetine has likewise been found to counteract space motion sickness. It can also partly protect against the damage resulting from excess glutamate and other excitotoxins.

A new neuroprotective property of vinpocetine has just been discovered: it can lower the production of inflammatory cytokines. Together with other phosphodiesterase inhibitors, vinpocetine has been shown to lower the production by the microglia of a major inflammatory compound known as tumor necrosis factor-alpha (TNF-alpha).

Some alternative clinicians believe that if we could truly control inflammation, we could prevent Alzheimer's disease. This view is based on the proven effectiveness of anti-inflammatories such as ibuprofen in lowering the risk of Alzheimer's disease. The problem with commonly used pharmaceutical anti-inflammatories is their side effects. Vinpocetine and other natural anti-inflammatories (fish oil, vitamin E, estrogens, many antioxidants including bilberry extract and green tea catechins) appear to be a nontoxic alternative.

Vinpocetine is an alkaloid, in the same family as caffeine and nicotine, both known to be very effective cognitive enhancers. Nicotine increases the release of acetylcholine and dopamine, and improves both short-term recall and long-term potentiation. But while caffeine and nicotine each have well-known drawbacks, vinpocetine appears to be safe and non-addictive. It would not be surprising if vinpocetine shared nicotine's protective benefits against Alzheimer's disease and Parkinson's disease, without the problem of addiction. An interesting side benefit of vinpocetine is that it has also been found to protect against both gastric and cerebral damage induced by alcohol, against kidney problems caused by renal vasoconstriction, and against retinal damage caused by the hepatitis B virus.

Enhancing Short-Term Memory

Another natural memory enhancer, Huperzine A-an extract from the Chinese club moss-appears to maintain higher acetylcholine levels by inhibiting acetylcholinesterase, the enzyme that breaks down acetylcholine. While it appears to be a promising adjuvant agent in the treatment of Alzheimer's disease, it is still too early to say whether it is desirable for people who have only minor memory deficit. Huperzine A is a great short-term memory booster that can be taken in doses of 50 mcg to 100 mcg first thing in the morning for special situations where maximum cognitive function is required. While Huperzine A appears to be safe for special situations, daily use could cause a neurotransmitter imbalance that could lead to undesirable complications such as acetylcholine overload. Huperzine A should not be taken more than a few times a week at the most.

Hormone of memory and good cheer

Pregnenolone was discovered during the 1930s and was extensively studied at first, particularly in connection with job performance and as a therapy for arthritis. Then it faded into oblivion as other hormones, notably synthetic forms of cortisone, became more trendy, not to mention lucrative for the drug industry.

Now we are witnessing a revival of interest in pregnenolone-after 60 years, it's gaining popularity alongside DHEA. Pregnenolone functions largely as a pro-hormone. Produced primarily in the adrenals, it is also the primary precursor of all the steroid hormones, the first hormone to be formed from cholesterol, the raw material for all steroids.

The levels of pregnenolone go down with aging. By the time we are 75, we have only 40% of the pregnenolone we had when we were 35. Besides aging, stress, disease, hypothyroidism, exposure to toxins and depression all result in low pregnenolone levels. Patients suffering from depression have been found to have pregnenolone levels less than half those found in nondepressed persons. These decreased levels of pregnenolone have been found in both unipolar and bipolar depression (the manic-depressive disorder). In job-performance studies, subjects reported better mood when taking pregnenolone. Like estrogen and DHEA, pregnenolone seems to have a pleasantly stimulatory effect on the brain, making one feel sharp without that wired, jittery feeling that may come from too much caffeine, for instance.

While many people know that DHEA and its sulfate, DHEA-S, are very abundant in the brain, few know that the brain levels of pregnenolone and pregnenolone sulfate are 10 times as high as those of DHEA. Pregnenolone could be called our primary neurosteroid. It is produced not only in the adrenals, but also in the brain-a finding first reported by the famous French steroid researcher, Dr. Etienne-Emile Baulieu. The peripheral nervous system can also manufacture pregnenolone, possibly for the purpose of maintaining the myelin sheath.

Pregnenolone is somewhat like ginseng. It improves energy, endurance and ability to cope with stress. Studies using factory workers, college students and airline pilots all found that pregnenolone effectively counteracts fatigue. When you are under stress, pregnenolone gives you an extra edge. When you are relaxed, however, you tend not to feel much difference. This may be particularly true of younger people. The elderly, who are more seriously deficient, seem to appreciate pregnenolone's extra energy boost more keenly.

In the 1940s, it was established that pregnenolone facilitates learning and helps us perform any task in which memory is involved. But pregnenolone's chief claim to fame is the fact that this pre-hormone has been found to be the most effective memory booster yet discovered in animal studies. It has been shown to increase the release of acetylcholine and to modulate NMDA (aspartate/glutamate) receptors in a way that suggests that pregnenolone stimulates central cholinergic communication. It also seems to modulate enzyme activity, calcium-ion flow through cell membranes, protein turnover and other complex reactions involved in memory function. Together with DHEA, pregnenolone also synchronizes the firing of the neurons. A decline in pregnenolone thus makes all mental function more difficult.

There is some anecdotal evidence suggesting that pregnenolone may be especially effective in elderly women as a restorer of energy and mental clarity, and as an antidepressant.

Even a small amount of supplemental pregnenolone may affect the quality of sleep. Most studies find that pregnenolone, like DHEA, increases the amount of REM sleep, which appears to be play a role in the formation of memory.

Like progesterone, pregnenolone is also important for repairing the brain and the spinal cord in case of injury. Pregnenolone is a precursor to progesterone in the body.

Caution: Men diagnosed with prostate cancer are advised to avoid pregnenolone because of the possibility of conversion into androgens.

The effects of deficiency

One area that we are barely beginning to investigate is pregnenolone's influence on various enzymes. One of the enzyme groups stimulated by pregnenolone is the cytochrome P-450 enzyme system, an important defense against various toxins and carcinogens. Thus, by helping the liver detoxify carcinogens, pregnenolone helps protect against cancer. Like many other steroids, pregnenolone also appears to modulate the immune response. Low levels of pregnenolone in aged individuals correlate with depression, cognitive decline and increased rate of cancer. Similarly, when cholesterol is excessively lowered, and thus the synthesis of pregnenolone is hampered, we see depression, cognitive impairment and more cancer.

Pregnenolone levels in premenopausal women have been found to be the highest during the luteal (progesterone) phase of the menstrual cycle. PMS sufferers have reported relief from their symptoms when they use pregnenolone. Since PMS is largely an inflammatory disorder, this action may be due to pregnenolone's anti-inflammatory effects. The overall hormone balancing effect may also be involved, particularly the conversion into progesterone.

At the same time, like DHEA and progesterone, pregnenolone seems to protect against the destructive consequences of elevated cortisol, such as weakening of the immune system. Cortisol levels increase with aging, while pregnenolone levels diminish. Probably the older one gets, the more crucial it is to take both DHEA and pregnenolone to correct this imbalance between the pro-oxidant, neurotoxic stress hormones and the beneficial steroids.

It is possible that pregnenolone's anti-inflammatory effects help protect against Alzheimer's disease, which has a marked inflammatory component.

Brain boosters

Image with Caption

Alpha lipoic acid has
emerged as a new
star in brain boosting,
in addition to
the neuroprotective
such as acetyl-l-carnitine
and CoQ10.

There are a variety of other supplements that may enhance your brain longevity program. Among these is alpha lipoic acid, which is both an antioxidant and a metabolic enhancer and has emerged as a new star. It is joined by neuroprotective energy-enhancers: acetyl-L-carnitine and coQ10.

The nervous system also needs the benefits of antioxidants and anti-inflammatories such as vitamin E, shown not only to protect the membranes but also to restore damaged neurotransmitter receptors, and fish oil. After all, fish eating has been documented to correlate with a dramatic lower risk of Alzheimer's disease. Neuroprotective regimens should also include the catechins in green tea extract, and/or the proanthocyanidins in grape seed extract and similar compounds in bilberry extract.

High-potency ginkgo is also highly recommended. In addition to being a documented cognitive enhancer, it has recently been found to extend life span in rats. Improvement in Alzheimer's disease patients has been noted with doses of 240 mg and higher.

Getting enough sleep and rest is extremely important. We must also take measures to reduce cortisol, which has neurotoxic effects. Meditation and stress reduction are effective measures, as are supplements such as DHEA, pregnenolone, and KH3. Chronic stress, today the daily condition of millions, causes an increase in free radicals (both oxygen and nitric oxide-based) and inflammatory cytokines. Fortunately most of the compounds mentioned here are both excellent antioxidants and anti-inflammatories; vitamin E and green tea catechins are stellar examples. Finally, vitamin C is extremely important for the brain. Besides functioning as an antioxidant, it also enhances the synthesis of key neurotransmitters, including acetylcholine and dopamine. Niacin (B3) also helps manufacture neurotransmitters, including the calming GABA. Interestingly, yet another B vitamin, thiamin (vitamin B1) has turned out to be a potent antioxidant, helping other antioxidants such as vitamin E to destroy free radicals.


Remember: unless you slow down your aging, aging is going to slow you down. It will make you increasingly physically and mentally disabled, sluggish, forgetful and depressed, ultimately making life not seem worth living. Fortunately, you can fight back with lifestyle, the right diet and the right supplements.


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