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Brain function plays a major role in how much energy we have , how we handle stress, whether our immune system is up to par, and, in general, how much zest we have for life. Concentration, memory and mood — whether we are fifteen and struggling with math or sixty-five and looking forward to an active retirement, these matter. Nutrients which support brain health should be a part of any supplementation program.

Begin with the basics. When building a house, you start with the foundation; when building brain health, you look to the health of the body as a whole. Several studies have shown that merely supplementing the diet with the B vitamins and vitamin C can improve mood and mental functioning. Other studies have demonstrated that good regular dietary habits are the best way to ensure optimal mental and behavioral performance, for instance, in children and adolescents. Therefore, a good balanced multi-vitamin and mineral supplement should be the backbone to any nutritional program.

Precursors to Brain Messengers
Proper nutrition is essential because it influences the production of the chemical messengers used by the brain and the rest of the nervous system. The messengers, called neurotransmitters, include acetylcholine, serotonin, noradrenaline (norepinephrine) and dopamine. Acetylcholine is significantly involved in mental acuity and memory. Nutrients influence neurotransmitters in various ways. For instance, vitamin B-5 (pantothenic acid) is necessary for the production of acetylcholine from the nutrient choline, which is provided by the diet in the form of lecithin found in foods such as eggs and soybeans. Lecithin, of course, has long been used as a supplement.

Omega-3 fatty acids play important roles in nerve membrane health. This shows up most strikingly in fetal and early childhood development. For instance, the children of mothers who supplemented with very-long-chain omega-3 fatty acids (docosahexaenoic acid/DHA) during pregnancy and lactation exhibited at higher IQ at 4 years of age compared to mothers taking omega-6 fatty acids, such as are found in corn oil. And a meta-analysis published in 2010 covering 17 trials examining children ages 5–16 years found that supplementing with micronutrients increased fluid intelligence and academic performance in healthy schoolchildren. It is classic that the ratio of dietary intake of omega-6 to omega-3 fatty acids should be in the range of 2:1 to 5:1. However, the ratio of omega-6 to omega-3 fatty acids in the Western diet has shifted from 5-to-1 to 15-to-1 in much of Europe and up to 40-to-1 in the U.S.

A closer look at a couple of often recommended supplements for brain nutrition helps to clarify how supplementation supports brain health. Phosphatidylserine (PS) is a member of the class of compounds known as phospholipids. PS, which is relatively well represented in human mother’s milk, is not abundant in the normal diet and is found in trace amounts in the usual sources of lecithin. Until recently, PS was only available from animal sources. PS in animal studies has shown an ability to induce the production of a number of neurotransmitters and/or to prevent their agerelated decline. These studies help to explain the clinical effects found in humans. For instance, PS stimulates acetylcholine output and the synthesis and release of dopamine. In aging rats, it even reset circadian and estrus rhythms. Of special interest, tests of the electrical signal strength associated with memory function indicated that PS reversed the loss of signal which marks memory decline. However, the benefits of PS are not limited to the production of neurotransmitters. PS, lecithin, choline and many other nutrients actually improve brain health by a surprisingly indirect route. The production of neurotransmitters and the manner in which these bind to cell receptors is strongly influenced by the nature of brain cell membranes, and it is these membranes which lecithin, etc. influence. This is a mechanism of action shared with the omega-3 fatty acids. Research indicates that PS may play a role in preparing the membranes of the cell to receive the signals sent by other cells.

Cytidine 5’-diphosphocholine, also known as CDP-choline and citicoline, is involved in the synthesis of the phospholipids, which make up the membranes of cells, especially the pathway involving phosphatidylcholine. When taken orally, citicoline is almost entirely bioavailable and releases its two components, citidine and choline, for dispersion to various parts of the body. Both elements readily cross the blood/brain barrier, become incorporated into brain membrane lipids, and increase the production of neurotransmitters in the central nervous system, including the synthesis of noradrenaline and dopamine. Citicoline also influences the mitochondria, hence the energy production, of brain cells. It improves memory in the elderly and has been shown to be useful as co-therapy in Alzheimer’s disease and Parkinson’s disease.

Matching Supplements to Age Groups
Surveys of nutritional needs suggest that around 80 percent of working adults may benefit from taking dietary supplements inasmuch as less than 20 percent get the “five a day” recommended portions of fruits and vegetables. However, as might be expected, the nutritional needs of different age groups vary. There are at least four groups that need to be addressed with regard to cognitive health:

  • Mothers from the point of being expectant through lactation
  • Children
  • Teenagers and college-age individuals
  • Those middle aged and later

Let’s start with the mother’s diet and that of children. Expectant and lactating mothers require additional nutrition inasmuch as they are supporting more than just their own metabolism. A recent nutritional review argues there, “are periods during perinatal development in which specific nutrients are required for optimal development, and there is growing evidence that optimal dietary intake of these nutrients, which include iodine, docosahexaenoic acid, choline, and folate, is important.” That review goes on to observe that the infant is not protected from the inadequacies of the diet of the mother. Neural development, as already noted, is especially dependent on omega-3 fatty acids, especially DHA.

The nutrient choline brings to mind the more general issue of good nutrition for mothers and their children. There are relatively few good food sources of choline nutrition available and the best of these undoubtedly is the egg. Now the notion that egg consumption is linked to poor cardiovascular health largely has been laid to rest, parents should look to fortified eggs as supplements to promote nutrition during peak brain development.

Insurance for general nutrition for children has been addressed in previous articles in this magazine. Here it need only be remarked that there are good children’s multivitamin/ mineral products available. Nothing replaces a good diet, but supplements with moderate amounts of selected nutrients offer good insurance against deficiencies and sometimes more than just deficiencies. Multivitamin supplementation, for instance, is associated with lower allergy rates in children.

Metabolism is dependent on age and body size and this, in turn, influences nutritional needs. Teenagers and those of college age, depending on body size, have nutritional needs more typical of adults. Usually, teenagers require more calories per pound body weight and more iron (for both sexes), especially if they are very athletic. Teenage girls engaged in endurance sports are particularly likely to require additional iron. At the same time, teenagers notoriously practice poor dietary habits. Hence, it comes as no surprise, for instance, that teenage males who consume more fish (hence more omega-3 fatty acids) do quite a bit better on cognitive performance tests. Similarly, micronutrient supplementation may be associated with an increase in fluid intelligence and academic performance in healthy schoolchildren.

Age-related Mental Decline
Americans today are living longer than in the past and this has led to increasing concerns about losing cognitive, memory and other mental abilities. This can range from forms of mild cognitive impairment to Alzheimer’s disease. There are both overlaps and disjunctions in terms of the causes of the various types of mental decline. Researchers have noted that certain types of physical changes in the brain are related, probably causally, to dementia. Asymptomatic cerebral infarcts — which lead to tissue death — are an important cause of dementia in the elderly. This is to say that local obstructions in the brain of the blood supply and oxygen are linked to dementia. Atherosclerosis of the intracranial arteries — independent of infarction — is an independent and important risk factor for dementia.

Alzheimer’s disease is generally thought of as being linked to beta-amyloid plaque development, and this is true as far as it goes. However, it turns out to be the case that beta-amyloid in its appropriate role is required for aspects of memory, hence the real story involves its inappropriate accumulation and accompanying toxicity. Epidemiology studies, including both regional incidence and the analysis of specific risk factors for Alzheimer’s disease, indicate that substantial prevention of the disease in the 50 –70 percent range is a practical possibility for the United States. Brain aging, including conditions such as Alzheimer’s disease, should not be viewed as if it takes place separately from the deterioration of other bodily systems. It long has been established that elevated blood sugar levels, which is to say, diabetes and pre-diabetes, are linked to the rate of various forms of dementia. Glycation, a deleterious form of modification of protein and lipid macromolecules in which a sugar inappropriately binds to the molecules, has been linked to diseases such as diabetes, Alzheimer’s, and Parkinson’s as well as physiological aging more generally.

A wide variety of nutrients have been shown to be useful. The combination of vitamins C and E, although not necessarily either alone, protects against Alzheimer’s disease. In the case of vitamin E, there is ever mounting evidence that gamma-tocopherol and forms other than alpha- tocopherol are protective against Alzheimer’s disease. Indeed, there is increasing evidence that vitamin E consistently delivers its expected benefits with chronic ingestion only when taken in conjunction with appropriate nutrients capable of regenerating the vitamin E radical. This means, especially, alpha-lipoic acid and coenzyme Q10. Integrative treatment including multivitamins, vitamin E, alpha-lipoic acid, omega-3 and coenzyme Q10 has been shown not only to slow the rate of cognitive decline in already medically ill patients for 24 months, but even to improve cognition and memory functions.

In general, those supplements that protect the arteries by promoting endothelial wall integrity should be good for the brain, as well. Similarly, supplements and habits that prevent weight gain and diabetes are good for the brain. And, of course, nutrients important for nerve membrane health, such as omega-3 fatty acids (especially DHA), phosphatidyl serine (PS) and phosphatidylcholine are perhaps the best known of the brain nutrients. Alpha- GPC (L-alphaglycerylphosphorylcholine, also known as choline alfoscerate) is another phospholipid metabolite found concentrated in neuronal membranes. Made from lecithin, alpha-GPC is extremely well absorbed and crosses the blood brain barrier. In the brain, alpha-GPC supports brain function and learning processes by directly increasing the synthesis and secretion of acetylcholine. It protects neurons and improves signal transmission by serving as a precursor to membrane phospholipids.

Not following certain bad habits also is in order. At the beginning of the Nineteenth Century, in America we consumed only on the order 17–18 pounds of sugar per person per year. Today consumption stands at around 143 pounds per person per year and an increasing percentage of this refined sugar is in the form of high-fructose corn syrup (HFCS). Quite simply, increased fructose intake is a risk factor for dementia.

What About Mood?
The food/mood connection has long been recognized. The cup of coffee pickme- up is a mood elevator, as often is the consumption of carbohydrates to self-manipulate serotonin levels, and so forth and so on.

Improving general health as we age often improves mood. For instance, those looking to improve depressed mood and fatigue might try propionyl-L-carnitine (glycine propionyl-L-carnitine is available as a dietary supplement) plus acetyl- L-carnitine. The omega-3 fatty acids DHA and EPA, likewise, improve not just health, but also mood. And, for older adults, another of vitamin D’s virtues is to boost mood.

Authoritative reviews, such as that of the RAND Corporation on S-adenosylmethionine (SAMe), indicate that there is substantial evidence in support of nutritional approaches to protecting and promoting brain health, including protecting against depression and mood disorders. In 2010, a study was published that took previous finding a bit further. The unique quality of the study was that it looked at individuals with major depression already being treated with serotonin re-uptake inhibitors and discovered that SAMe supplementation improved the percentage who responded to treatment.

There are still other ways of increasing brain levels of the various neurotransmitters. For instance, serotonin levels, which are closely linked to depression, to the ability to withstand stress and to in such conditions as attention deficit disorder (ADD), may be influenced by supplementing with vitamin B-6. This vitamin, as is true of SAMe, improves serotonin production in the brain. Yet another way to influence serotonin levels is to supplement with its immediate precursor, 5-HTP, which is readily available in stores.

Concluding Thoughts
Health food store shelves are now filled with ever more exotic solutions to everyday problems. Those issues which depend upon brain health are not exceptions. However, before the reader jumps on the bandwagon of the latest and greatest, he or she might try simple brain nutrition. Most of us would do well to listen to the advice that often “less is more.” No one should take a supplement to accomplish those things which can be better achieved by eating breakfast every day, taking a 20 minute morning walk in the sunshine and getting enough sound sleep at night. And when it comes to brain supplements, start with the basics. These include multi-vitamin and mineral supplements and then precursors to neurotransmitters plus omega-3 amino acids.

Dallas Clouatre, PhD

Dallas Clouatre, Ph.D. earned his A.B. from Stanford and his Ph.D. from the University of California at Berkeley. A Fellow of the American College of Nutrition, he is a prominent industry consultant in the US, Europe, and Asia, and is a sought-after speaker and spokesperson. He is the author of numerous books. Recent publications include "Tocotrienols in Vitamin E: Hype or Science?" and "Vitamin E – Natural vs. Synthetic" in Tocotrienols: Vitamin E Beyond Tocopherols (2008), "Grape Seed Extract" in the Encyclopedia Of Dietary Supplements (2005), "Kava Kava: Examining New Reports of Toxicity" in Toxicology Letters (2004) and Anti-Fat Nutrients (4th edition).