Molecular Tools for Maintaining the Brain

Molecular Tools for
Maintaining the Brain

Integrating a variety of supplements is
the best way to forestall cognitive decline
By Will Block

Man is a tool-using animal. … Without
tools he is nothing, with tools he is all.

— Thomas Carlyle

an the toolmaker.” For centuries, man’s toolmaking ability was considered to be our defining characteristic—the one trait that was not shared by any other species. Whereas all other creatures made do with whatever they found in their natural environment, we humans made things with which to improve our environment and the quality of our lives. Biologists taught that our species was thus fundamentally different in this regard, and we took a certain pride in our natural superiority. It was satisfying to know that we were special.

Then Jane Goodall shattered the illusion by discovering that chimpanzees make tools too, and from a scientific point of view, the last major distinction between humans and animals bit the dust. Other examples of toolmaking and tool use have been observed both in the field and in the laboratory—and not just with primates, but also with lower animals, such as rodents and birds. They constitute proof of directed intelligence and rational forethought, a domain we once considered exclusively our own. As a species, we have been properly humbled. And yet … look around you. Is what we have achieved through science and technology not truly fantastic?

Our Brains—The Final Frontier

Almost everything technological that we now take for granted would in times past (and not all that long ago) have been considered fantastic too … in the sense of being pure fantasy. Innumerable things that would have seemed impossible to our ancestors can now be bought at any Wal-Mart. Similarly, future generations will surely produce technological marvels that we now, with our limited knowledge and brainpower, would find inconceivable. We will someday be viewed with pity for having lived in such a primitive time as this.

But the wonders of technology to be enjoyed by our descendants will depend on the groundwork we are laying here and now. One thing that all of us can do is to push at what is probably the final frontier in the domain of tool use: our own brains. Although we have become accustomed to seeing many other parts of the human body modified or repaired with a variety of mechanical or electronic devices (e.g., artificial knee joints or cardiac pacemakers), our brains seem singularly remote from the possibility of such high-tech tinkering—except through the use of certain chemical compounds.

What Do Brain Tools Look Like?

We all know of the tremendous power of some substances—especially alcohol and narcotics—to affect the workings of our mind and, if used to excess, to damage our brain cells. Even without such abuse, however, our brains suffer the accumulated consequences of just plain living—an injudicious diet, too little exercise, too much stress, chronic low-level inflammation, and the relentless onslaught of free radicals generated primarily by cellular respiration, the very process that makes life possible in the first place.

For those of us—and this means everyone on earth—who face the prospect of a gradual slowdown of cognitive function (memory, learning, attention, concentration, etc.) as we grow older, it would be wonderful to have a “molecular toolkit” with which to counter the ravages of time, so as to keep our brains functioning like those of our younger selves. We want tools—whether in the form of synthetic drugs or, preferably, natural supplements—that hold the promise not just of retarding the progression of age-related cognitive decline but also, perhaps, even of preventing it altogether.

They Look a Lot Like Supplements

Among the supplements that seem to hold great promise in this regard are the herbal alkaloid galantamine, which enhances the brain’s acetylcholine levels and activity, and the nitrogenous alcohol choline, a precursor to acetylcholine and phosphatidylcholine, both of which are vital for proper brain function. A particularly important class of substances is antioxidants, such as lipoic acid, coenzyme Q10, quercetin, green tea polyphenols, and vitamins C and E. Two others, the omega-3 fatty acids and turmeric curcuminoids, are discussed in the sidebars.

Omega-3 Fatty Acids Fight Brain Plaque

Two of the worst things that can happen to your tissues and organs are oxidative stress and inflammation. Both are caused mainly by molecular species that are produced by your own body, and both cause long-term harm of many kinds. They’re implicated in a host of chronic diseases, including cognitive decline and dementia, and in aging itself. Anything that can counteract both of them is welcome indeed.

So let’s say “Welcome” to the omega-3 fatty acids, also known as omega-3 fish oils because they’re found mainly in coldwater fish, notably shad, mackerel, salmon, herring, anchovies, and tuna. They’re a special type of polyunsaturated fatty acids (PUFAs), which are much healthier than saturated fatty acids.

The two most valuable omega-3s are DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid). DHA is especially important because it’s an integral component of cell walls in the nervous system. Just as a brick wall that’s missing a lot of bricks will be weak and ineffective, a deficiency of DHA molecules in the brain can cause impairment of both the structural and functional integrity of delicate neurons (brain cells).

Although the omega-3s are best known for their exceptional value in reducing the risk of heart disease, they also improve brain function and help prevent age-related cognitive impairment and Alzheimer’s disease.* For example, whereas high intakes of total fat, saturated fat, and cholesterol increase the risk for dementia, a high intake of omega-3 fatty acids reduces that risk, in middle-aged as well as elderly people.1,2 Furthermore, low levels of DHA are a significant risk factor for Alzheimer’s, whose victims typically have reduced brain levels of DHA.3

*For coverage of the myriad benefits of these compounds, see “Omega-3 Fish Oils—Fats That Are Good for Everyone” (July 2002), “DHA Is Essential for Brain Function, Heart Health, and More” (August 2002), “Omega-3 Fatty Acids May Have Anticancer Benefits” (February 2003), “Fish Oils Help Maintain Brain Power” (April 2004), and “Omega-3 Fish Oils Reduce Mortality from All Causes” (July 2004).

Researchers at UCLA and the U.S. Department of Veterans Affairs have shed new light on the inverse relation between DHA and the risk for Alzheimer’s disease.4 Using elderly “transgenic” mice that were genetically engineered to be highly susceptible to Alzheimer’s, they found that dietary DHA intake had a profound effect on the formation and accumulation of amyloid-beta, the proteinaceous plaque that damages or destroys certain regions of the brain in Alzheimer’s victims. This neurotoxic plaque is both a result of and a cause of oxidative stress (from free radicals) and inflammation.

Examination of the mouse brains revealed that a DHA-enriched diet reduced the total amount of amyloid-beta by more than 70% compared with DHA-free or normal diets. The “plaque burden,” a measure of the extent to which the plaques covered the affected regions, was reduced by about 40% on average; among the regions where the reduction was greatest was the hippocampus, which is dedicated primarily to cognitive functions.

The researchers explained how increased DHA levels could reduce both oxidative stress and inflammation, thereby reducing plaque formation in the mouse brains. They stated that their data correlate well with the results of human epidemiological studies demonstrating a reduced risk for Alzheimer’s disease in people having a proper daily intake of omega-3 fatty acids.

Recent estimates suggest that Americans consume only 100–200 mg/day of omega-3s from fish.5 That’s far below the 650 mg/day recommended for maintaining good general health, and very far below the 1000–4000 mg/day believed to be required for maintaining healthy blood lipid levels and a healthy cardiovascular system.6 Thus, unless we start binging on fish every day, we’re not likely to get optimal amounts of omega-3 fatty acids, except through supplementation.


  1. Kalmijn S. Fatty acid intake and the risk of dementia and cognitive decline: a review of clinical epidemiological studies. J Nutr Health Aging 2000;4:202-7.
  2. Kalmijn S, van Boxtel MPJ, Ocké M, Verschuren WMM, Kromhout D, Launer LJ. Dietary intake of fatty acids and fish in relation to cognitive performance at middle age. Neurology 2004;62:275-80.
  3. Conquer JA et al. Fatty acid analysis of blood plasma of patients with Alzheimer’s disease, other types of dementia, and cognitive impairment. Lipids 2000;35:1305-12.
  4. Lim GP, Calon F, Morihara T, Yang F, Teter B, Ubeda O, Salem N Jr, Frautschy SA, Cole GM. A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model. J Neurosci 2005;25(12):3032-40.
  5. Kris-Etherton PM, Taylor DS, Yu-Poh S, et al. Polyunsaturated fatty acids in the food chain in the United States. Am J Clin Nutr 2000; 71(Suppl):S179-88.
  6. Kris-Etherton PM, Harris WS, Appel LJ, for the Nutrition Committee of the American Heart Association. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 2002;106:2747-57.

Turmeric Fights Brain Plaque

Ranking very high in the list of antioxidant and anti-inflammatory supplements are curcumin and the related curcuminoids, a class of polyphenolic compounds found in the curry spice turmeric (Curcuma longa). Turmeric has been used for millennia in India and Southeast Asia, not just for flavoring foods but also for its medicinal properties. We now know that these properties derive primarily from turmeric’s exceptional antioxidant and anti-inflammatory potency. (Because of the latter, curcumin is called a nonsteroidal anti-inflammatory drug, or NSAID; it’s widely used for the treatment of arthritis.)

Perhaps not coincidentally, the elderly residents of rural India, who eat large amounts of curry, appear to have the lowest incidence of Alzheimer’s disease in the world.1 If there is indeed a causal connection there, it may be because curcumin and the curcuminoids suppress the formation of amyloid-beta, the plaque that destroys the brain cells of Alzheimer’s victims. The same UCLA and Department of Veterans Affairs research group that demonstrated the ability of the omega-3 fatty acid DHA to accomplish this in the brains of elderly transgenic mice that were prone to Alzheimer’s disease has found similar results, with similar mice, using curcumin.2

The results showed that dietary curcumin beginning at 17 months of age (that’s pretty old for a mouse) reduced plaque levels by 85% and reduced the plaque burden by 33%. In addition, laboratory experiments showed that curcumin strongly inhibited the formation of amyloid-beta plaques and promoted the disintegration of plaques that had already formed. It attacked both the amyloid-beta and the oxidative stress and inflammation caused by amyloid-beta. The researchers summarized their findings by saying (in their unedited online preprint),

The final proof of any anti-amyloid effect is in vivo [in a living organism] testing. Because amyloid accumulation begins decades before diagnosis, anti-amyloid therapy would ideally begin prior to clinical symptoms. Approaches that remain efficacious at advanced stages of amyloid accumulation are clearly needed; and our in vivo observations, suggest curcumin may even be beneficial even after the disease has developed.

Although in vivo here refers to mice, not humans, this strong endorsement of the potential benefits of curcumin by leading authorities in the biochemistry of amyloid-beta will, one hopes, capture the attention of the medical profession—and not just in regard to brain health but also in regard to other benefits that are attributed to curcumin and the curcuminoids. These include their anticholesterol and antitumor effects (which may or may not be related to their antioxidant and anti-inflammatory properties).*

*For more detailed discussions of turmeric’s role in promoting good health, see “Turmeric May Help Prevent Alzheimer’s and Parkinson’s Diseases” (February 2002), “Turmeric Protects Your Brain Cells (July 2004), and “Turmeric Is ‘The Spice of Life’” (November 2004).


  1. Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci 2001;21:8370-7.
  2. Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS, Chen PP, Kayed R, Glabe CG, Frautschy SA, Cole GM. Curcumin inhibits formation of Ab oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem 2005 [online preprint dated Dec 7, 2004].

Taken alone, each of these substances offers certain benefits. But taking them alone makes no more sense than eating only one type of food, such as strawberries or pickles or turkey. Just as it’s wise to eat balanced meals for proper nutrition, it’s wise to take a variety of supplements for a given purpose so as to gain the combined benefits they can offer. An analogy in medicine is the common practice of simultaneously prescribing two kinds of antihypertensive drugs, such as a beta-blocker and an ACE inhibitor, for patients with high blood pressure; the combined benefits of the two are often better than either one alone.

Mind Foods Make a Toolkit

That it’s the same with supplements should surprise no one. The ones mentioned above can be thought of as “mind foods” for their special ability to nourish the brain and help protect it from undue harm. They’re compounds that, in combination, constitute a kind of molecular toolkit that can be highly valuable for the maintenance of healthy brain function—which, when you, uh, think about it, is about as important a kind of maintenance as there could be.

Although the use of nutritional supplements is, sadly, still alien to much of the medical profession in the United States (but not in Europe and most of the rest of the world), more and more doctors are willing to prescribe them, often together with the synthetic drugs they’re already prescribing. And why not? If the drugs are effective (despite their side effects) and the supplements are also effective, and if there are no adverse interactions among them, it stands to reason that patients will likely do better with both than with just one or the other. But if the supplements can make the drugs unnecessary, so much the better.

Integrate, Integrate!

One example of dual therapy is the use of multivitamins and antioxidants taken together with prescription drugs designed for treating Alzheimer’s disease. Of course, without carefully controlled clinical trials, it’s impossible to differentiate the benefits due to the supplements from those due to the drugs. But what really matters, ultimately, is helping people to be as healthy as possible in their particular circumstances, even if we don’t fully understand the details.

That being true, it makes sense to carry this approach a big step further by integrating our supplement and drug (if any) interventions with appropriate lifestyle improvements, such as a healthy diet, regular exercise, stress management, and abstention from tobacco and excessive alcohol consumption. Indeed, one could argue that healthcare practitioners who do not actively try to integrate all these strategies for the benefit of their patients are irresponsible.

One Small Step at a Time … for Mankind

Every time you open your molecular toolkit and use a mind food to help nourish and maintain your brain, you are making one small step forward in mankind’s collective experience with these remarkable substances. It is only through such collective experience—of researchers, healthcare practitioners, and consumers alike—that we can make further progress along the dimly lit road to healthier brains that retain their youthful edge indefinitely. Our descendants, if they’ve learned their manners, will thank us for it.

Will Block is the publisher and editorial director of Life Enhancement magazine.

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