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Brain Health Influenced by Diets and Supplements

By Yousry Naguib, Ph.D.

Vitamin Retailer magazine, June 2004

The brain is the center of thought and emotion. It makes us conscious, emotional, and intelligent. It is the control center for movement, sleep, thirst, and virtually every other vital activity necessary to survival. It controls emotions Ė love, hate, fear, anger, elation, and sadness; and receives and processes countless signals sent from other parts of the body and from the external environment.

Over the past three decades, research studies have shown that the chemistry and function of both the developing and the mature brain are influenced by diet, and dietary supplements. For example, folate deficiency has been associated with neural tube development during early gestation; essential fatty acids have been shown to play a role in the development of brain and visual function in infants, and tryptophan and tyrosine are essential for the production of the brain neurotransmitters serotonin and catecholamines, respectively.

Folic acid

Recent research has strongly linked folic acid to brain development. The incidence of neural tube defects, spina bifida, is notably higher in children of women who are folate deficient during pregnancy and can be reduced by folic acid supplementation during pregnancy.

This relation has been demonstrated in a randomized, double-blind trial involving folate supplementation of women before conception [1]. The study involved administering 4000 Ķg folate daily, a dose much higher than the recommended daily intake. Nevertheless, no toxicity was evident and the outcome was remarkable. In women consuming the supplement, 6 infants (out of 602 births) developed neural tube defects, whereas in women receiving no folate supplement, 21 defects (out of 602 births) occurred. The study concluded that folate supplementation produced a 72% protective effect against the occurrence of neural tube defects.


Phospholipids, such as phosphatidyl serine and phosphatidyl choline, are fats containing phosphorus. They are found naturally in the body, and in food sources like lecithin. They rejuvenate cognitive functions, memory and learning skills that decline with age.

Phosphatidyl serine (PS) is enriched in the brain. It has been demonstrated in clinical trials to improve memory, concentration, word recall, and mood in middle-aged and elderly subjects with dementia and age-related cognitive decline. PS also relieves symptoms of anxiety and depression in elderly women [2].

Preliminary findings with humans though are limited, showed some benefits [3,4,5]. For older adults with moderate cognitive impairment, PS has produced consistently modest increases in recall of word lists.

PS in soft gel capsules undergoes significant degradation resulting in a shorter shelf-life. To overcome this problem, Degussa Food Ingredients introduced Leci-PSģ20V phosphatidyl serine which has greater stability in soft gels.

Lecithin is a naturally occurring mixture of the diglycerides of stearic, palmitic, and oleic acid, linked to the choline ester of phosphoric acid, commonly called phosphatidyl choline (PC). Choline is the precursor to the neurotransmitter acetylcholine, which plays an important role in memory. The amounts of choline in the brain can be altered by dietary choline intake, in the form of either free choline or phosphatidyl choline (lecithin) [6,7].

Dietary choline and lecithin have been studied as potential memory enhancers, in particular in patients with probable Alzheimerís disease. The outcome of these studies has been that neither choline nor phosphatidylcholine offers much improvement in memory [8]. It is argued that the extent of functional losses due to changes beyond those involving cholinergic neurons may be so great as to obscure any beneficial actions of choline or lecithin.

Dimethyl-aminoethanol (DMAE), also known as Deanol, is related to choline, and is assumed to increase brain acetylcholine. In one study DMAE was given for 4 weeks to 14 senile (mental impairment associated with aging) patients, to determine the safety of DMAE and whether or not it reduces cognitive impairment. The dosage was gradually increased to 600 mg three times daily during the first two weeks, with no adverse effects. By the third week ten patients had reduced depression, irritability and anxiety; and 4 patients were unchanged. No apparent changes in memory were observed. The study suggested that although Deanol may not improve memory, it may produce positive behavioral changes in some senile patients [9].

Alpha-glycerylphosphoryl choline (A-GPC) is another source for choline. A-GPC is similar to PC, except without the fatty acid chains (A-GPC is not a phospholipids).

In an open clinical trial, the efficacy and tolerability of 1g/day A-GPC was compared with 1g/day cytosine diphosphocholine (CDP). Both treatments were given intramuscularly for 90 days in patients with mild to moderate vascular dementia. At the end of the treatment, both treatments produced a definite symptomatic improvement and showed good tolerability [10].

In an earlier trial A-GPC was shown to enhance Growth hormone (GH) secretion in young and elderly individuals after stimulation by GH releasing hormone [11].

Polyunsaturated fatty acids (PUFAs)

PUFAs are essential constituents of structural lipids in cellular membranes, which influence the activities of membrane-linked functional molecules, such as receptors and enzymes.

Sixty percent of the human brain is fat, 25 percent of which is omega-3 docosahexaenoic acid (DHA). DHA is an essential nutrient for brain development in infants. Infants get their DHA from their motherís milk or the diet. Premature infants often have low levels of DHA and are at higher-than-average risk of neurological disorders. Children with hyperactivity or attention deficit disorder also tend to have low levels of DHA [12].

A study in the Lancet reported that infants given a DHA-enriched formula had better problem-solving ability at 10 months compared with infants who had a standard low-DHA diet [13]. It was suggested that higher problem solving scores in infancy is related to higher childhood IQ.

The connection between dietary DHA and brain development was also made in premature infants. In a randomized, double-blind trial, infants were supplemented with DHA (0.35 percent) and Arachidonic acid (0.75 percent) in a formula designed to closely match that of motherís milk. Infants in the supplemental group showed a significant increase in the Mental Development Index after 18 months. The implication is that the presence of DHA in the diet could directly influence DHA accretion in the brain [14].

Depression has been associated with significantly low levels of EPA and DHA in cell tissue contents (red blood cell membrane, plasma). In an 8-week, double-blind, placebo-controlled trial, comparing omega-3 PUFAs (9.6 g/day) with placebo in 28 patients with major depressive disorder; patients in the omega-3 PUFA group showed a significant improvement in the symptoms as compared to those in the placebo group. The study suggested that omega-3 PUFAs could improve the short-term course of illness and were well tolerated in patients with major depressive disorder [15].

Ginkgo biloba

Preparations based on special extracts of Ginkgo biloba are popular both in Europe and the United States. The primary active constituents of ginkgo biolba leave include flavonoid glycosides and the diterpenes ginkgolides; the latter are potent inhibitors of platelet activating factor.

Clinical studies have shown that standardized leaf extracts of Ginkgo biloba exhibit therapeutic activity in a variety of disorders, including Alzheimerís disease, failing memory, age-related dementias, and boor blood circulation.

The benefits of Ginkgo for cognitive dysfunction have been evaluated in two meta-analysis studies. In the first study, published in 1992, six out of forty double-blind trials compiled from the literature met the quality criteria. These trials showed benefits-for as few as 17 percent of the elderly patients to as many as 71 percent of the younger patients-at dosages of 160 mg per day [16].

In the 1998 meta-analysis study, only four trials met the quality criteria. The analysis revealed only small benefit for Alzheimerís patientsí quality of life. The four trial employed doses of 120 or 240 mg of Ginkgo biloba extract per day [17]. Ginkgo biloba should not be used with blood-thinning medication.

Coenzyme Q10

Coenzyme Q10 (CoQ10) may be beneficial in preventing brain degenerative disorders such as Parkinsonís disease. In a multi-center, randomized, placebo-controlled, double-blind trial, eighty subjects with early Parkinsonís disease who did not require treatment for their disability received either a placebo or CoQ10 at dosages of 300, 600, or 1200 mg/day. Subjects were followed up for 16 months or until disability requiring drug-treatment had developed. At the end of the trial, CoQ10-group showed less disability than the placebo, and the benefit was greatest in subjects receiving the highest dosage. The study concluded that CoQ10 appears to slow the progressive deterioration of function in Parkinsonís disease [18].

Acetyl-l-carnitine (ALC)

ALC participates in cellular energy production, a process especially important in neurons. Studies of patients with probable Alzheimer's disease have reported nominal advantages over a range of memory tests for ALC-treated patients relative to placebo groups [19]. However, a subsequent study found ALC benefited patients ages 65 or less [20].


Vinpocetine, derived from vincamine (an alkaloid found in the periwinkle plant Vinca minor), is an excellent vasodilator, acting by direct relaxation of the vascular smooth muscle; and cerebral blood flow enhancer in patients with cerebrovascular disorders [21]. In clinical trials involving patients suffering from mild-to-moderate vascular dementia, vinpocetine benefited memory and cognitive performance [22,23].

Bacopa (Bacopa monniera)

Bacopa, also known as brahmi, has been used for thousands of years in Indiaís traditional Ayurvedic medicine to improve learning, perception, memory, and concentration. Bacopa leaves contain steroidal saponins of which bacosides have the ability to enhance nerve impulse transmission and thereby strengthen memory and general cognition.

In an open trial conducted in India 35 adult patients with anxiety were given 12 g per day of the dried plant in syrup form, for four weeks. Concentration and immediate memory span were significantly increased, and mean total anxiety level was significantly decreased. Other symptoms, including nervousness, insomnia, headache, and irritability were significantly improved [24].

St Johnís wort (SJW)

St Johnís wort (Hypericum perforatum) is widely used herbal supplement for mild-to-moderate depression. SWJ has an encouraging safety profile. However, recent reports indicate the possibility of interactions with prescribed drugs [25]. Some of such interactions may cause either adverse effects or treatment failures.

SJW has been shown to lower the plasma concentration of certain drugs, including immunosuppressant drugs (cyclosporine, a drug taken by transplant patients to fend off the immune systemís tendency to reject a transplanted organ), warfarin (anticoagulant), digoxin (is a drug originally derived from the foxglove plant, Digitalis lanata and used for congestive heart failure), birth control pills, and protease inhibitors (used to treat persons with HIV infection).

Apocynum venetum

A standardized extract from Apocynum venetum, sold under the trade name Venetron by Soft Gel Technologies, Inc., has been found to shorten the immobility time in an animal model (forced swimming test) for antidepressant activity at the dosage of 15 mg/kg body weight, indicating possible antidepressant activity. This effect was comparable to that of the antidepressant drug Imipramine (15 mg/kg), and to St. Johnís Wort extracts (250 mg/kg). This antidepressant effect might be related to the bioactive flavonoids hyperoside and isoquercitrin in Venetron, which are also present in St. Johnís wort extract [26].


Huperzine A, an alkaloid isolated from a club moss (Huperzia serrata), is a powerful and reversible inhibitor of acetylcholinesterase developed by the Chinese Academy of Sciences. It is currently in phase III trials in China for the treatment of patients with Alzheimerís disease [27].

Huperzine works in a manner similar to some prescription drugs to combat Alzheimerís related memory loss, by inhibiting the enzyme acetylcholinesterase, and thereby blocking the breakdown of acetylcholine (a brain chemical essential to memory) to choline.


Feverfew (Tanacetum parthenium L.) is a popular herbal remedy often advocated for preventing attacks of migraine. A very recent (2004) report examined the evidence from five double-blind randomized controlled trials (343 patients) assessing the clinical efficacy of feverfew versus placebo for preventing migraine. Results from these trials were mixed and did not convincingly establish that feverfew is efficacious for preventing migraine [28]. However, in an earlier study, the same researchers concluded that feverfew is likely to be effective in the prevention of migraine [29].

Amino acids

The amino acids tryptophan, 5-hydroxytryptophan, and tyrosine play an essential role in brain health as precursors to neurotransmitters, the brainís signal carriers.

Tryptophan is the precursor to the neurotransmitter serotonin. Oral administration of tryptophan can modify sleep and mood via its actions to stimulate neuronal serotonin production and release [30].

The outbreak 10 years ago of a toxic response to nonprescription preparations of L-tryptophan diminished interest in this supplement. The toxic response, termed eosiniphilia myalgia syndrome (EMS), was characterized by neurologic and pulmonary complications that resulted in a small number of deaths. Because the occurrence of the syndrome appeared to be correlated with the use of tryptophan, it was thought that a contaminant (termed peak X) in the product, not tryptophan itself, was responsible for EMS. Pharmaceutical-grade tryptophan preparations have never been associated with symptoms of EMS, suggesting that pure tryptophan preparations are safe.

Tyrosine is the precursor of the catecholamine neurotransmitters dopamine, norepinephrine, and epinephrine. In one study, tyrosine administration was shown to improve cognition and performance in soldiers under stressful conditions [31,32].


Antioxidants help neutralize tissue-damaging free radicals, which become more prevalent as organisms age. It is hypothesized that increasing antioxidant levels in the organism might retard or reverse the damaging effects of free radicals on neurons.

Low-bush blueberries (Vaccinium angustifolium Aiton) have a high antioxidant activity; and it was suggested that consumption of blueberries would protect neurons from stroke-induced damage.

In one study, rats were fed diets containing 0% (control) or 14% blueberries for 6 weeks, and then subjected to ischemia followed by hypoxia. One week later, rats on blueberry-supplemented diet lost only 17% of neurons in the ischemic hippocampus as compared to 40% in control rats. The data suggest that inclusion of blueberries in the diet may decrease ischemia-induced brain damage [33].

With the proper diet and the right dietary supplement one can improve cognitive function and combat age-associated memory loss.


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