The Brain-Diet Connection

Among the hypothesized mechanisms for halting plaque development is that DHA leads to lower levels of a compound, called presenilin, needed for amyloid production. “If you’re preventing the production of presenilin,” Rabon-Stith says, “then you’re reducing the amyloid plaque being formed. And, if you’re reducing the development of this amyloid plaque, in a sense you’re reducing the risk of Alzheimer’s disease developing.”

DHA isn’t the only omega-3 with a track record in cognitive function. “If you look at a lot of the problems of aging,” Rao points out, “underlying them is an excess of inflammation. As you grow older, oxidative stress keeps increasing on your body and in your brain cells. And, just because of your body’s regular day-to-day working, inflammation in your tissues increases.” While DHA helps the brain from a structural perspective, the anti-inflammatory protection comes from EPA.

“EPA is very important in anti-inflammatory cascades,” Rao says, “and actually, I, for one, believe that EPA is more important than DHA.” He concedes that “you would need to design a study to look at that,” but maintains that “omega-3s, especially fish oils where you have both EPA and DHA, really help, because you’re attacking both the inflammation part and the structural part.” As for efficacious doses, he cites studies recommending anywhere from 400 mg to 1 gram of EPA plus DHA per day. “So, for example, if you’re making a food product, 32 mg of EPA plus DHA is not going to cut it,” he says. “We think it’s important to have, say, 100 to 150 mg per serving, because then you can make a legitimate case that if you eat a reasonable number of servings per day, then by the end of the day, you’re getting 400 mg to 1 gram.”

Hot-headed

To be sure, inflammation accounts for many of aging’s depredations. As researchers tease out the mechanisms behind age-related cognitive decline, they’re paying increasing attention to dietary antioxidants’ ability to reduce inflammation and oxidative stress. Research has identified advantages in everything from antioxidant-rich blueberries to zinc.

Scientists in Taiwan, publishing in the Journal of Agricultural and Food Chemistry (2008; 56(3):859-864), found that when the antioxidant flavanones hesperidin, hesperetin and neohesperidin found in citrus were added to PC12 cells in vitro—a laboratory model for neuronal development—they protected the cells from DNA damage and assault by hydrogen peroxide. “These dietary antioxidants are potential candidates for use in the intervention for neurodegenerative diseases,” the authors wrote.

An epidemiological study published last year in the American Journal of Epidemiology (April 2007; 165:955-965) also concluded that adequate lifelong selenium intake may slow age-related cognitive decline. Selenium is an important constituent of antioxidant enzymes known as selenoproteins, and researchers found decreased selenium levels, as measured in fingernail samples, correlated with lower cognitive scores in a population of rural elderly Chinese. The researchers emphasized the importance of long-term selenium intake, as the areas of the brain that take the longest to develop are also those that show the earliest signs of Alzheimer’s disease.

Late last year, scientists at USDA’s Human Nutrition Research Center at Tufts University, Boston, determined that diets containing 2%, 6% or 9% walnuts reversed several benchmarks of brain aging, as well as age-related motor and cognitive declines, in elderly rats. Researchers speculate walnuts’ polyphenol antioxidants may halt the free-radical damage that leads to inflammation, and might go beyond merely quenching free radicals to actually blocking oxidative stressors’ chemical signals. An added plus: the levels used in the study, when translated to a human diet, are entirely reasonable, as 6% works out to the equivalent of around 1 oz. of walnuts per day, and 9% equals about 1.⁵ oz.

Antioxidants also help protect the phospholipid component of neural cell membranes, Chaudhari says. Phospholipids such as lecithin, phosphatidylcholine, acetylcholine and phosphatidylserine make critical structural contributions to brain cells. “Phosphatidylserine has been studied by quite a few companies,” he says, “and it will maintain and improve cognitive abilities, concentration, learning abilities and memory recall, and it makes you have better focus.”

However, once oxidized, these phospholipids are “highly unstable molecules,” Chaudhari notes. “When blood is circulating, it contains iron, metals and other pro-oxidants that will create free radicals there, too. So, you’ve got to protect those phospholipids in order to maintain the integrity of cognitive function.”

Not just any antioxidant will do, however. Phospholipids exhibit bipolarity, and Chaudhari stresses the need to include both hydrophilic and lipophilic antioxidants—selenium, tocopherols, vitamin C—in any protective formula. “If you have the dual antioxidant backup system,” he says, “that will protect both the water-soluble and the water-insoluble portion.”

Reading the tea leaves

Green tea has its own set of antioxidants, such as epigallocatechin gallate (EGCG), with their own set of benefits. But the compound that may be most relevant to cognitive function is the non-protein, nonessential amino acid L-glutamic acid-gamma-monoethylamide—better known as L-theanine.

Scott Smith, vice president, Taiyo International, Inc., Minneapolis, says L-theanine is found only in the Camellia sinensis leaf. Of course, tea also contains caffeine, another neuroactive compound well known for its stimulative effects. But, he says, “there’s always been a contradiction to tea in that it’s been known as a calming, relaxing beverage, and yet it has fairly high levels of caffeine.” The explanation, he says, is that L-theanine, when present at its natural levels in the tea leaf, acts as an antagonist to caffeine’s less-desirable side effects. “Thus, while you still have the stimulant and the caffeine in your body, you don’t have the jitters, nausea, headaches, light-headedness, or difficulty focusing or concentrating.” When isolated and administered at even higher levels in its isomerically pure form, L-theanine actually promotes calmness, relaxation, focus and stress reduction, he says.

L-theanine is absorbed in the small intestine and eventually circulates to the brain, where it passes through the blood-brain barrier. Once there, “it’s actually normalizing our brain neurotransmitters,” Smith says. Per Taiyo literature, it apparently participates in the formation of the inhibitory neurotransmitter GABA, which itself blocks the release of dopamine and serotonin to the effect of enhanced relaxation. “So, if we have an imbalance in brain neurotransmitters, L-theanine brings us back into a normal state.” It won’t go beyond that normal state, he says, precluding the drowsiness that accompanies other relaxation-promoting ingredients like kava.

If it sounds like a drug, it’s not. “We market it as a food,” Smith says. In 2006, the company submitted the product to FDA for GRAS affirmation, and the following year, “we had a letter of no objection with no limits on servings for use in food and beverages.” What’s more, he says, L-theanine is a refreshingly compliant ingredient compared to the finicky, highly labile green-tea EGCG. “For the formulator, it’s tasteless, colorless and a very stable compound,” he says. And the consumer actually notices it working. “When we consume it, we feel it within 20 to 30 minutes,” he says. “When you actually feel something happening, the repeat business is pretty high for our customers.”

Smith says original studies of the product’s efficacy were in animal models, but human clinical trials continue to substantiate its benefits. Based on those clinicals, recommended levels range from 50 to 200 mg, after which point benefits level off. If your neurotransmitters are already balanced, he adds, no amount of L-theanine will have an added effect, precluding any worries about overdose.

As for where the amino acid is showing up, “we’re seeing a lot of activity in beverages,” Smith says. And, while the product’s calling card is its ability to calm, many drinks tout its effects on focus, concentration and alertness, positioning it as an alternative to those wild-eyed, hyper-caffeinated energy drinks already on the market.

Toward a better-fed brain

So, what’s not to like about any product that claims to stave off age-related memory loss, depression, Alzheimer’s or even a failing grade on the trig test? Nothing—if such products actually work. So, as Greenwood asks: “Are there likely opportunities for food manufacturers? I guess I would say, yes, there is a lot of evidence out there, and there are substances that they could take advantage of.”

How best to do that, though, is the formulator’s challenge. “It comes down to the whole issue of risk reduction and how you communicate risk reduction to the individual,” Greenwood says. “Can we promise that if they eat X, Y or Z that they’re not going to develop dementia? Of course we can’t. But on the other hand, it would be consistent with lowering the likelihood of developing it if they did.”

Ultimately, you don’t have to be a genius to design a diet for a better brain. “It basically comes down to some reasonable common themes that continue to come up in terms of what we need for neuroprotection,” Greenwood says. That would be plenty of antioxidant-rich fruits, nuts and vegetables, fatty fish and an all-around varied diet. “There’s a lot to it that doesn’t have to go into the rocket science arena, for lack of a better term,” she says. “And that’s because a lot of it is really common sense.”

Kimberly J. Decker, a California-based technical writer, has a B.S. in Consumer Food Science with a minor in English from the University of California, Davis. She lives in the San Francisco Bay area, where she enjoys eating and writing about food. You can reach her atkim@decker.net.