Will Block

Take acetylcholinesterase - please. It's one of the more unloved substances in the human body, because it acts as a kind of molecular butcher, cleaving other molecules in half with grim efficiency. But at least it's highly selective, always seeking and destroying only the acetylcholine molecule, which it splits into acetate and choline. Such specificity is characteristic of all enzymes - proteins that are designed to carry out just one task, through their catalytic activity.

Acetylcholine, as most readers probably know, is a versatile neurotransmitter, a messenger molecule that acts throughout the central and peripheral nervous systems to mediate a host of vital functions, including many related to cognition and memory. It is a molecule devoutly to be desired in ample quantities, not only so we can keep all our marbles, but so they can stay bright and shiny for the endlessly varied game of life.  

WHEN GOOD MOLECULES GO BAD, AND VICE VERSA

Why then, did Mother Nature unleash an enzymatic assassin to keep cutting the poor acetylcholine molecules in half?  Because - and this is as true of biomolecules as anything else - too much of a good thing is a bad thing (think glucose and diabetes, e.g.). There must always be checks and balances and feedback mechanisms to ensure that there is just enough of what we need, neither too little nor too much. And so there are "good" molecules that we need for optimal health, and "bad" molecules (which aren't really bad, because they serve a necessary purpose) that keep the good ones from creating havoc through overabundance.

Furthermore, in a chemical analogue to military electronic countermeasures technology, there is a second tier of "good" molecules that serve to jam the actions of the bad ones, when necessary, by inhibiting their ability to perform their assigned functions. One such is huperzine A, an acetylcholinesterase inhibitor - bad for acetylcholinesterase and therefore good for acetylcholine. And, like Chinese boxes, there are yet other molecules that inhibit the inhibitors . . .

In this cats-and-mice game, there is, as always in living organisms, a delicate balance to be maintained. And, as always, the balance can get skewed as we age, for some reasons that we understand and many more that we don't. In any case, if acetylcholinesterase gains the upper hand and unduly depletes our stores of acetylcholine, really bad things can happen, such as Alzheimer's disease - not that there is a clear cause and effect there (few things, including Alzheimer's, are that simple), but there is a strong correlation that can't be ignored.

GOOD MOLECULE, HUPERZINE!

Huperzine A (HupA for short), an alkaloid found in the Chinese herb Huperzia serrata, is effective in improving cognitive and memory abilities in humans, including those with Alzheimer's disease.  In China, where HupA is used for treating Alzheimer's and myasthenia gravis, medical scientists have studied its effects on the mental functions of elderly Alzheimer's patients.¹

In a rigorously designed and controlled experiment, 60 patients aged 52 to 80 with impaired faculties were treated with synthetic HupA (200 micrograms twice daily) or placebo for 60 days. They were evaluated with a huge array of both psychological and physiological tests to determine their mental and physical health before and after the treatment - and, in particular, to determine whether it made any difference if the HupA was administered in the form of capsules or tablets.

Based on four of the most important psychological tests, including memory function, the improvement rates in both groups ranged from 43% to 70%; there was no statistically significant difference between the capsule group and the tablet group.

The researchers also set out to observe the action of HupA on the damaging effects of oxygen free radicals in the patients' plasma and erythrocytes (red blood cells). Biochemical tests showed significant improvement, although not to the reference values for healthy people in the same age group. The authors speculate that long-term treatment with HupA might be required to optimize the results.

The study also reconfirmed the previously demonstrated safety as well as efficacy of HupA.^2,3 The only side effects noted were mild to moderate nausea and insomnia, again with no difference between the capsule and tablet groups.

YOUNGSTERS ALSO BENEFIT FROM HUPERZINE

When a nutrient that improves mental function in the aged does the same in the young, that's really interesting. And that is what Chinese researchers found, in a study designed to determine the efficacy of HupA on memory and learning in adolescents.⁴ They selected 34 matched pairs of apparently normal junior middle school students whose only significant complaints were of poor memory and difficulty in learning.

The pairing was done in terms of age, sex, memory quotient, and overall psychological health, to ensure that comparisons would be meaningful. Using these criteria, the researchers found no statistically significant baseline differences between the students in the two groups, one of which was to be treated with HupA, the other to receive a placebo.

In a double-blind trial, one member of each pair, chosen randomly, was given 100 micrograms of synthetic HupA twice daily for four weeks, while the other member received the placebo. The students' memory quotients were measured before and after the trial, and their academic performance in their Chinese, English, and mathematics lessons was monitored as well.

The results: At the end of the study, the HupA group scored significantly better than the control group on standard memory tests described as "accumulation," "recognition," "reproduction," "association," "tactual [tactile] memory," and "number of recitation," but not on tests of "picture memory" or "understanding." They had also done significantly better in their Chinese and English lessons, but not in math. No side effects of any kind were noted.

HUPERZINE IS PREFERABLE TO PRESCRIPTION DRUGS

Huperzine A is superior to the drugs tacrine and donepezil, which are acetylcholinesterase inhibitors widely prescribed for Alzheimer's disease. There is no question that these drugs are effective, but it is our view that chemical compounds derived from natural sources are preferable to those invented by chemists, because the natural ones are typically safer and freer from unwanted side effects.

References

1. Xu SS, Cai ZY, Qu ZW, Yang RM, Cai YL, Wang GQ, Su XQ, Zhong XS, Cheng RY, Xu WA, Li JX, Feng B. Huperzine-A in capsules and tablets for treating patients with Alzheimer's disease. Acta Pharmacol Sin 1999 Jun;20(6):486-90.

2. Xu SS, Guo ZX, Wang Z, Du ZM, Xu WA, Yang JS, et al. Efficacy of tablet huperzine-A on memory, cognition, and behavior in Alzheimer's disease. Acta Pharmacol Sin 1995;16:391-5.

3. Xu SS, Xie HB, Du ZM, Tong ZH, Shi QC, Lu KM, et al. Efficacy of tablet huperzine-A on memory and cognition in patients with benign senescent forgetfulness. Chin J Clin Pharmacol Ther 1997;2:1-4.

4. Sun QQ, Xu SS, Pan JL, Guo HM, Cao WQ. Huperzine-A capsules enhance memory and learning performance in 34 pairs of matched adolescent students. Acta Pharmacol Sin 1999 Jul;20(7):601-3.