6. Can Supplements Really “Boost” Brainpower

One of the fastest-growing segments of the dietary supplement industry is the market for products claiming to protect your memory or “boost” your brainpower. These range from mega-doses of vitamins your body does actually need (though not necessarily in such quantity) to novel concoctions such as Asian herbal remedies or proteins originally found in jellyfish. Do the claims for such products stand up to scientific scrutiny? While at least some evidence supports brain benefits for the nutrients we looked at in the last chapter, especially when obtained from food, other supplements sold for brain health lack this foundation in nutrition. Rather than providing extra vitamins, minerals or essential fats that the body needs, these ingredients are marketed more like the magic elixirs of the old “medicine shows.”

That in itself does not mean these “brain-boosting” pills are of no value, of course. In fact, scientists have recently reported some intriguing results about ingredients you may never have heard of. But other studies largely debunk supplement products touted for brain benefits. In this chapter we will seek to separate fact from fiction, hope from hype.

Buyer Beware

The first thing you need to know about products sold as “dietary supplements” is that they are regulated differently from foods or prescription drugs. Products that actually supplement what your body needs, such as extra calcium or vitamin D, are lumped in with herbal remedies that don’t truly “supplement” a proven nutritional need. (No one needs extra ginseng, for example, and there is no evidence that you need any at all.)

While the U.S. Food and Drug Administration (FDA), Department of Agriculture (USDA), and Federal Trade Commission (FTC) have broad powers to ensure the safety of foods and medications and regulate health claims, dietary supplements are governed under the 1994 Dietary Supplement Health and Education Act (DSHEA). Under DSHEA, the manufacturer is responsible for the accuracy and truthfulness of health claims, which must be submitted to the FDA within 30 days of use but are not verified by the government.

You’ve probably seen the disclaimer on product labels and ads complying with the loose rules of DSHEA: “This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.” Nonetheless, manufacturers make carefully crafted promises—“structure-function claims” permitted under DSHEA—that their products, for example, “enhance mental sharpness and support long-term brain health” (not “prevent Alzheimer’s disease”) (see Box 6-1, “Does This Enhance…or Make You Wonder?” on page 62).

What Are You Really Buying?

There is also no guarantee of the purity of most products sold as dietary supplements, or even whether they actually contain the ingredients listed on the label. Many consumers were shocked at the 2015 news that four out of five popular herbal remedies sold at some of the nation’s leading retailers didn’t contain any of the promised ingredients. DNA testing of store-brand products instead detected fillers—including wheat and legumes, possible risks for people with intolerances or allergies. For example, pills sold as ginkgo biloba, a Chinese plant touted for memory benefits, actually contained powdered radish, ground houseplants, and wheat.

An earlier study by scientists at the University of Guelph in Canada reported that oe-third of 44 herbal remedies tested contained no trace of the supposed main ingredient (see Box 6-2, “Getting What You Pay for in the Supplement Aisle”).

You might even be getting unregulated pharmaceutical-grade drugs in your “brain-boosting” supplements (see Box 6-3, “Brain-Boosting Supplements: Buyer Beware,” on page 64).

Nasty Surprises

The National Center for Complementary and Integrative Health (NCCIH), which explores possible benefits from such products, also cautions that some herbal remedies may interact with medications or pose risks if you have medical problems or are going to have surgery. Information about possible side effects is limited, and what information is available is usually not included on labels.

Also, many supplements contain more than one compound, or you might take more than one type of supplement at a time, and there is no knowledge of how these compounds might interact. If you do choose to use such products, tell all your health care providers that you’re taking them.

The Evidence on Herbal Supplements

Ginkgo Biloba: Wasting Your Money?

Probably the best-known supplement promising brain benefits is ginkgo biloba, a Chinese herbal remedy derived from the leaves of the ginkgo tree. Annual sales of ginko biloba mount up to $250 million in the U.S. Ginkgo biloba is also the most thoroughly studied supplement, and the results are mostly negative. The Ginkgo Evaluation of Memory (GEM) study, a large and long-running clinical trial, has repeatedly reported that consumers are probably wasting their money on ginkgo products.

GEM is a well-designed study—a randomized, double-blind, placebo-controlled trial, the type considered the “gold standard” of medical research. It involved 3,069 participants, ages 72 to 96, at six academic medical centers. Researchers reported no difference in the rate of total dementia or in the rate of Alzheimer’s-type dementia between those given ginkgo and those administered a placebo. Participants already suffering mild cognitive impairment saw no benefit from ginkgo biloba in preventing the progression to dementia. Subsequently, GEM also found that twice-daily doses of 120 milligrams of ginkgo extract worked no better than a placebo in slowing cognitive decline.

Those negative results were further supported by a French study testing 120 milligrams of ginkgo twice a day versus placebo among 2,854 patients, ages 70 and up. Participants were free of dementia, but had reported memory problems to their physicians. After five years of follow-up, 61 of those randomly assigned to ginkgo and 73 in the placebo group developed dementia—a difference scientists said was not statistically significant. An accompanying editorial in The Lancet Neurology suggested users of the herbal extract “might now consider letting it go.”

Testing Ginseng and Grape-Seed Extract

Other plant products popularly marketed for brain benefits, among other claims, include ginseng and grape-seed extract. These have not been as extensively studied as ginkgo, which also means the evidence for any possible benefits is thin. A review by the National Center for Complementary and Integrative Medicine concluded there’s not enough evidence to recommend these or any herbal remedies for protection against dementia and Alzheimer’s disease.

Only a few high-quality clinical trials have been conducted on Asian ginseng in Alzheimer’s disease, so the evidence pro or con is scant. According to the review, “Research results to date do not conclusively support health claims associated with the herb.”

As for grape-seed extract, a few preliminary studies have looked at possible effects on the brain, but “there is currently insufficient evidence to determine if grape-seed extract is helpful in the prevention or treatment of cognitive decline or Alzheimer’s disease.” The Center is pursuing further research on grape-seed extract and brain disorders, as well as for possible heart benefits.

Other Ingredients

You might encounter other supplement ingredients with purported brain benefits, often sold in combination with the better-known ginkgo biloba. The only way to know what you’re getting in supplements sold for memory or “brain power” is close scrutiny of the Supplement Facts label. Few of these less-familiar ingredients have been studied extensively, and even those for which preliminary results seem somewhat promising should be considered, at best, unproven:

• Vinpocetine: Sometimes added to supplements containing ginkgo, vinpocetine is a synthetic compound made to resemble a substance found naturally in the periwinkle plant. It has been used in Europe to protect against strokes because it’s thought to increase blood flow to the brain. By extension, vinpocetine is also hypothesized to improve brain function. In studies of older adults with memory problems associated with poor brain circulation or dementia-related disease, vinpocetine produced significantly more improvement than a placebo on tests of attention, concentration, and memory. Studies of its effectiveness on healthy humans are rare and have been very small.
• Phosphatidylserine (PS): A fat-like substance found naturally in cell membranes, especially in the brain, PS is extracted from soybeans and, like vinpocetine, often sold in combination with other memory-boosters. Promoters may boast that PS is the only such ingredient with a qualified health claim approved by the FDA; they are less likely to repeat the FDA’s qualification that “there is little scientific evidence for this claim.” Nonetheless, it’s worth noting that a few small, short-term studies have recently shown promising results with PS in elderly subjects already suffering from memory problems. In one case, 100 milligrams of PS plus 80 milligrams of phosphatidic acid significantly improved memory, mood and cognition in elderly subjects. Patients with Alzheimer’s disease showed a stabilizing effect on daily functioning.
• Huperzine A: This moss extract is a Chinese herbal remedy thought to increase levels of acetylcholine, a neurotransmitter, in the brain. One review of the evidence in 10 trials in patients with Alzheimer’s disease or vascular dementia concluded that Huperzine A could “significantly improve” cognitive scores. Alzheimer’s patients saw “significant improvement of cognitive function measured by memory quotient (MQ).” Overall, the review found that Huperzine A is “a well-tolerated drug that could significantly improve cognitive performance in patients with Alzheimer’s disease or vascular dementia, but we need to use it with caution in clinical treatment.” Those findings, however, do not mean that Huperzine A protects against cognitive decline in healthy individuals, as it is claimed to in some supplement formulations.
• Apoaequorin: This protein “originally found in jellyfish,” as noted in countless commercials during the nightly news, has been the subject of only limited research. Those studies have all involved scientists employed by the supplement maker and only one has been published in a journal rather than on the company’s website; that journal specializes in “alternative” and “mind-body” medicine. In 2012, the FDA issued a warning letter saying the product’s claims crossed the line to being an “unapproved new drug.” The agency also cited more than 1,000 “adverse events” related to the product, some of which required hospitalization.

There’s also the question of whether any protein could survive the digestive system, which breaks down proteins into their constituent amino acids, and then subsequently follow the bloodstream into the brain. Could any tiny amount of “jellyfish” protein that might reach the brain have any benefit? That has yet to be proven by the scientific standards required of products sold as drugs, not “supplements.”

Curcumin: From Spice to Supplements

Not to be confused with the spice called cumin, curcumin is the key component in turmeric, which gives curry powder its distinctive orange color. Also found in stores selling vitamin and other supplements, curcumin has antioxidant as well as anti-inflammatory properties. People in curry-eating countries have much lower rates of Alzheimer’s disease than people in the United States, leading scientists to suspect that curcumin could help mental functioning. In fact, a study of more than 1,000 non-demented elderly Asians found that those who reported consuming the most curry performed better on the Mini-Mental State Examination than those who consumed less of the spice.

A recent randomized, double-blind, placebo-controlled trial tested both the immediate and four-week effects of a 400-milligram curcumin supplement in 60 healthy adults ages 60 to 85. One hour after supplementation, those receiving curcumin showed significantly improved performance on tests of working memory and sustained attention. After four weeks of treatment, curcumin was associated with significant improvements in working memory and mood. No negative side effects were observed and, in fact, subjects given curcumin saw significant reductions in both LDL and total cholesterol levels. In addition to anti-inflammatory effects, research at UCLA suggests that curcumin helps the immune system remove beta-amyloid, the protein that forms damaging plaques in the brains of Alzheimer’s patients. Curcumin also has a metal-chelation effect, binding to metals such as copper, cadmium, and lead that are toxic to nerve cells (see Box 6-4, “The Jury’s Still Out on Curcumin”).

Creatine: Building Strong Brains?

Creatine is an amino acid-like compound that is obtained naturally in the diet through the consumption of high-protein foods, such as meat, fish, and eggs. The body also synthesizes creatine from amino acids. Used by athletes and body builders to boost muscle mass and improve performance in intense physical competitions, such as cycling or rowing, creatine is one of the most popular dietary supplements, with sales of $400 million a year. Its possible benefits for the brain as well as the body were summarized in a recent review: “In relation to the brain, creatine has been shown to have antioxidant properties, reduce mental fatigue, protect the brain from neurotoxicity, and improve facets/components of neurological disorders like depression and bipolar disorder.”

Supplements of creatine are generally believed to be safe and well tolerated by adults in amounts up to five grams per day; there’s not enough evidence one way or the other about greater amounts.

The review concluded, “The combination of these benefits has made creatine a leading candidate in the fight against age-related diseases, such as Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, long-term memory impairments associated with the progression of Alzheimer’s disease, and stroke.”

Cellular Energy

According to Tufts experts Patricia J. Allen, PhD, and Kristen E. D’Anci, PhD, “The therapeutic value of oral creatine supplementation to treat brain-related disorders is related to its ability to increase cellular energy reserves. The beneficial effects of creatine are also strongly supported by the pivotal role it plays in buffering metabolic processes to prevent energy depletion and neuronal death.”

Although they caution that research remains limited, Allen and D’Anci add, “Empirical evidence on the neural and behavioral effects of creatine is steadily growing to support the safety, tolerability, and efficacy of creatine to protect the brain from neuronal damage and to improve cognitive function.”

Extra for Low Intake

In animal testing, mice and rats fed a diet enhanced with creatine displayed improved memory and learning ability. For healthy humans, supplemental creatine significantly improved working memory and intelligence scores among vegetarians and vegans, who are likely to have low creatine intake.

Extra creatine also helped relieve the mental fatigue after an exam and boosted mental performance of young men suffering from sleep deprivation. In a test of healthy nonvegetarians not subjected to any unusual stress, however, creatine supplementation did not improve scores on a variety of cognitive tests.

Creatine and Cognition

Other studies have shown that patients with Alzheimer’s disease have decreased activity of a creatine enzyme in key areas of the brain, compared with healthy people of the same age. It’s possible that abnormalities in this creatine enzyme contribute to the abnormal metabolism and neuron loss and dysfunction seen in Alzheimer’s patients. The beta-amyloid plaques associated with Alzheimer’s may inactivate or degrade this key creatine compound. Creatine also prevents oxidative damage, suggesting it might protect against beta-amyloid-induced oxidative stress in patients with Alzheimer’s disease.

People suffering from age-related cognitive decline might also benefit. One study found improved performance on tests of verbal and spatial short- and long-term memory.

While more research is needed before recommending creatine as a tool against Alzheimer’s and cognitive decline, the evidence to date is more encouraging than for other supplements more popularly touted as “brain boosters.”

Supplements for Mood and Behavior

Many other supplements are marketed as beneficial for mood, depression, sleep quality, and “energy”—mental factors that affect behavior, which in turn can indirectly affect cognition. The evidence for their effectiveness is mixed, though some may be safe alternatives to prescription medications. You should also exercise caution when taking any of these supplements with prescription drugs; tell your healthcare professional before taking any of these supplements.

St. John’s Wort Versus Depression

Clinical guidelines from the American College of Physicians-American Society of Internal Medicine state that St. John’s wort can be considered an option for short-term treatment of mild depression. A review of the evidence about St. John’s wort and major depression, published in the Cochrane Database, concluded that it was as effective as standard prescription antidepressants, with fewer side effects. The National Library of Medicine, however, concludes that although some studies have reported benefits for depression, others have not. One large study sponsored by NCCIH found that St. John’s wort was no more effective than placebo in treating major depression of moderate severity.

Keep in mind, also, that St. John’s wort has serious interactions with a long list of medications, including warfarin, so consult your physician before trying this herbal supplement. St. John’s wort was also among the herbal products targeted by a recent investigation as frequently failing to actually contain the listed ingredient.

Green Tea for Depression, Alertness

We’ve already seen how tea might benefit the brain in chapter 4. Green tea and green tea extract also may combat depression. In one Japanese study, elderly participants who reported drinking four or more cups of green tea per day were 44 percent less likely to have symptoms of depression than those drinking one cup or less per day. A similar relationship was seen for green-tea consumption and risk of severe depression. The NCCIH adds, “Some evidence suggests that the use of green tea preparations improves mental alertness, most likely because of its caffeine content.”

Valerian for a Good Night’s Sleep

Made from the root of a flowering plant, valerian has been used as an herbal remedy since ancient times. It may be effective against insomnia, although the NCCIH advises, “there is not enough evidence from well-designed studies to confirm this.” Moreover, “there is not enough scientific evidence to determine whether valerian works for other conditions, such as anxiety or depression.”

Valerian does not relieve insomnia as fast as standard sleep medications, and continuous use for several days, even up to four weeks, may be needed before an effect is noticeable. Some studies have found that valerian doesn’t improve insomnia any better than a placebo. Valerian should not be taken with alcohol or sedative medications.

Ginseng for Mental “Energy”

In addition to largely unsupported claims for cognitive benefits, ginseng is also promoted for improving “mental energy.” A review by the Life Sciences Research Organization found the scientific evidence for such claims regarding mood and cognition inconsistent, however. The National Library of Medicine similarly says there is insufficient evidence to conclude that ginseng is effective against stress or insomnia.

Ephedra: Dangerous Herb

Besides its popular use in weight-loss supplements, also ephedra has been touted for “increased energy.” An evergreen, shrub-like plant native to Central Asia and Mongolia, ephedra contains an active ingredient called ephedrine, which can powerfully stimulate the nervous system and heart. But ephedra’s risk of heart problems and stroke outweighs any benefits, according to the FDA, which in 2004 banned the sale of dietary supplements containing ephedra. The ban does not apply to traditional Chinese herbal remedies or to products like herbal teas regulated as conventional foods, so beware.

Downsides of Energy Drinks

You might also be tempted by the claims of so-called “energy drinks,” which have soared in popularity in recent years. The FDA has investigated reports of adverse events tied to these beverages, and cautions that these drinks are not alternatives to rest or sleep. The most common ingredients are caffeine, sugar, B vitamins, and amino acids. Although both caffeine and sugar can give you a short-term jolt, there are safer ways to obtain caffeine (as well as healthy phytonutrients), as we’ve seen in our discussion of coffee and tea, and sugar just adds calories.

Snake Oil?

It may have surprised you to read in this chapter that some supplements you’ve never associated with brain power (or may never have heard of)—such as curcumin and creatine—seem to be the most promising. On the other hand, products widely marketed for brain benefits, such as ginkgo biloba, appear to have modest effects at best. That’s why it’s important to keep up with the science of better brain power and stay skeptical about marketing claims, which are loosely regulated and may simply disguise what an earlier era would have called “snake oil.”

In any case, none of the evidence for these “brain-boosting” supplements compares to the proven benefits of a healthy dietary pattern. Your best insurance against cognitive decline as you age can be found in your fridge and pantry—not in pill bottles—as well as in other elements of a healthy lifestyle, which we’ll explore in the next chapter.

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