The following points highlight the eleven important dietary factors for brain function. The factors are: 1. Essential Fatty Acids 2. Amino Acids and Neurotransmitters 3. B Complex Vitamins and Neurotransmitters 4. Folic Acid and Brain Development 5. Iodine and Brain Development 6. Iron 7. Water 8. Other Nutrients in Brain Function 9. Anti-Oxidants in Brain Function 10. Foods and Brain 11. Fish.
Factor # 1. Essential Fatty Acids:
It is well known that the two essential fatty acids, linoleic and alpha linolenic are most important for brain function, n-3 PUFAs influence cognition during ageing. These are the prime structural components of brain cell membranes and are also an important part of the enzymes within cell membranes that transport valuable nutrients in and out of the cells.
The Eskimos who eat a lot of fish have a lower incidence of degenerative diseases of the central nervous system, such as multiple sclerosis. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are one diet-related factor suggested to influence cognitive decline during ageing. The n-3 long-chain (LC) PUFAs eicosa-pentaenoic acid (EPA) and docosa-hexaenoic acid (DHA) are crucial to brain development and normal brain functioning. DHA concentration in the brain decreases with age in humans.
After birth the DHA content of the brain in formula fed infants was below that of breastfed infants as the breast milk contains DHA. Thus, presence of DHA in the diet could directly influence DHA accretion in the brain. But hydrogenated or partially hydrogenated fat hinder the brain’s work. High-fat foods not only clog the arteries, but damage brain function.
DHA is particularly important to brain functioning due to its influence on neural membrane properties, which modulate cell signaling. Infants with low amounts of dietary DHA have reduced brain development and diminished visual acuity. The increased intelligence and academic performance of breastfed infants has been attributed in part to the increased DHA content of human milk. Experimental animals whose diets are low in DHA have been found to have smaller brains and delayed central nervous system development.
Some children with poor school performance because of ADD (Attention Deficiency Disorder) have been shown to have insufficient essential fatty acids in their diet. The underlying biochemical mechanisms are poorly understood. Improvements in mild memory complaints with 900 mg of DHA were reported by Yurko-Mauro et al. (2010). Positive effects were observed on Verbal Recognition Memory and significant decreases in resting heart rate with DHA indicating improved learning and episodic memory functions and cardiovascular benefits in age-related cognitive decline.
Cognitive deficits are ameliorated and memory performance is improved by DHA supplementation. DHA and EPA levels, either individually or in combination, have been associated with better cognitive function in normal older adults or reduced risk of cognitive decline, substantial inhibition of Aβ fibrillation and lower risk of developing dementia.
Ueda et al. (2011) showed that the senescence-accelerated mice given a high poly-unsaturated fatty acid diet had higher brain concentrations of poly-unsaturated fatty acid, better memory and greater longevity. Apart from improving memory, the reaction time of memory also improved in healthy, young adults on supplementation with DHA, whose habitual diets were low in the same.
The long-term dietary ω3 PUFA supplementation positively impacts the anxiety and cognitive performances in the adult mouse lemur and may improve the same in humans also. Increasing n-3 PUFA (DHA and EPA) intakes may reduce depressive symptoms and the risk of progressing to dementia in older people with mild cognitive impairment.
Some clinical evidence suggests that an ARA: DHA ratio greater than 1:1 is associated with improved cognitive outcomes. Combined supplementation of DHA with iron improved verbal and nonverbal learning and memory, particularly in children with anemia, and DHA and phytonutrient lutein showed cognitive benefits in older adults.
Factor # 2. Amino Acids and Neurotransmitters:
Tryptophan is the precursor to the neuro-transmitter serotonin. Numerous studies showed that the availability of this amino acid to brain neurons directly influences the rate at which it is converted to a neuro-transmitter. Administering either the amino acid itself or meals that raise tryptophan availability to serotonergic neurons rapidly stimulated serotonin production and enhanced serotonin release in neurons thus producing changes in brain function. In humans, administration of oral tryptophan can modify sleep and mood via its actions to stimulate neuronal serotonin production and release.
The radial arm maze and the passive avoidance tests on animals showed that the increase in brain 5 Hydroxy-tryptamine metabolism following long term tryptophan administration may be involved in enhancement of memory. While single oral administration of tryptophan was not effective in memory enhancement, repeated intake significantly enhanced memory functions of rats as evidenced by the decreased latency time to reach the hidden platform in Water Maze test.
Older adults with mild cognitive impairment showed significant improvements in several measures of cognitive function when supplemented with an oily emulsion of DHA-phospholipids containing melatonin and tryptophan for 12 weeks, compared with the placebo. In a double-blind study for 14 days, S-Adenosyl Methionine (SAMe) supplementation was found to result in significant improvements in depressive symptoms compared to 22 per cent of the Imipramine treated patients.
Tyrosine is the precursor to the catecholamine neurotransmitters dopamine, norepinephrine and epinephrine. Analogous to the ability of tryptophan to stimulate serotonin production, elevating tyrosine concentrations in brain catecholamine neurons, particularly dopamine and norepinephrine neurons, can stimulate transmitter production. Tyrosine administration appears to improve cognition and performance in soldiers under stressful conditions.
Further work is required before the usefulness of tyrosine is established or accepted. Mahoney et al. (2007) and O’Brien et al. (2007a and b) demonstrated that cold exposure degrades cognitive performance and supplementation with tyrosine alleviates working memory decrements.
Factor # 3. B Complex Vitamins and Neurotransmitters:
B vitamins appear to slow cognitive and clinical decline in people with mild cognitive impairment, in particular in those with elevated homocysteine. In a multivariate analysis, Moorthy et al. (2012) showed an association between low plasma vitamin B-12 concentrations and poor Mini-Mental Status Exam (MMSE) scores and higher depression scores; and between low vitamin B-6 concentrations and low MMSE, attention span and executive function. Walker et al. (2012) reported that long-term daily supplementation of folic acid and vitamin B-12 promotes performance on immediate and delayed memory but not processing speed among community-dwelling older adults with elevated psychological distress.
Choline is the precursor to another neuro-transmitter acetylcholine. Neuronal choline concentrations can be altered by dietary choline intake, in the form of either free choline or phosphatidyl-choline (lecithin). Oral choline and phosphatidyl-choline have found some application in brain functions involving cholinergic neurons. Choline and lecithin have also been studied as potential memory enhancers, on the basis of the notion that acetylcholine neurons in the hippocampus play an important role in memory and that enhancing transmitter production might improve memory.
Supplementing the maternal diet with additional choline (approximately 4.5 times the amount in normal rodent chow) dramatically improved the performance of the adult trisomic offspring in a Radial Arm Water Maze task and partially normalized adult hippocampal neurogenesis thus contributing functionally to their improved spatial cognition.
Factor # 4. Folic Acid and Brain Development:
During the past decade, clinical observation has strongly linked folic acid to brain development. The incidence of neural tube defects (e.g. 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; ideally, supplementation should begin before conception. The clearest demonstration of this relation derives from a study by the Medical Research Council (MRC) Vitamin Study Research Group, which conducted a randomized, double-blind trial involving folate supplementation of women before conception.
Folate deficiency, by impeding DNA, protein, or lipid synthesis, could conceivably influence neuronal and glial growth and proliferation during critical points in neural tube development, leading in some cases to induce neural tube defects. Hence, initiating supplementation before conception is important because the fundamental construction of the CNS occurs during the first trimester; a time when many women are unaware that they are pregnant.
Various biochemical actions of folate might be involved in the functioning of brain:
1. Maintaining adequate methionine pools for the synthesis of S-adenosylmethionine,
2. As a cofactor in methylation reactions in catecholamine synthesis and metabolism.
3. Maintenance of adequate amounts of tetrahydro-biopterin, and
4. A key cofactor in the synthesis of serotonin and the catecholamine neuro-transmitters.
These neurotransmitters are important in maintaining normal affective state (mood). Folate supplementation (15 mg/d) for 6 months showed improvements in the depressed and schizophrenic patients treated with standard pharmacotherapy. Intake of folic acid has been linked to other psychiatric conditions as well as to deficits in learning and memory, particularly in the elderly.
Shooshtari et al. (2012) showed that folic acid may improve both short- and long-term memories, dose dependently, although it affects motor balance at lower dose. Coenzyme Q10 and folic acid have also been shown to possess therapeutic and preventive effects on cognitive impairments in Alzheimer’s disease. The mechanism of effects of folic acid on cognition and motor coordination is yet to be understood.
Factor # 5. Iodine and Brain Development:
Iodine deficiency results in a global loss of 10-15 intellectual quotient points at a population level, and constitutes the world’s greatest single cause of preventable brain damage and mental retardation. Iodine is a key nutrient in the fetal development process, especially with respect to the brain. The associated disturbances due to maternal thyroxine deficiency range from increased neonatal morbidity and mortality and severe mental dysfunction, to hyperactivity, attention disorders and a substantial decrease of IQ of an irreversible nature in the progeny.
Young children are particularly at risk because the brain still needs iodine for its development during the first two years of life. Iodine deficiency affects the thyroid function and the mental development, and is the main cause of brain damage in childhood. In addition, iodine deficiency in children is responsible for disorders in physical and cognitive development and hypothyroidism.
There is much anecdotal evidence coming from long-standing observations in Europe supported by recent reports from China and India, indicating that iodine- deficient village populations suffer from general lethargy, poor work performance and defective school performance in children. These effects are due to hypothyroidism, particularly cerebral hypothyroidism. Recently, Liu et al. (2013) reported that the spatial learning and memory ability of 40-day-old marginal iodine-deficient rats had a downward trend compared with the normal control group.
Free thyroxine levels significantly decreased after pregnancy in rats with marginal iodine deficiency, affecting the expression of related proteins in the brain of offspring. As a consequence, iodine deficiency is the leading preventable cause of impaired mental function in the world, affecting as many as 2 billion people (35.2 per cent of the entire population).
A child’s performance at school is affected by impaired cognitive and motor development. It is because of these adverse effects on brain development that the 58th World Health Assembly passed a resolution to urge a renewed effort from the international community, including WHO and UNICEF, to address iodine deficiency in the 54 countries most affected.
Iodine supplementation given to school-age children improved performance on tests of intellectual functioning. Randomized controlled trials showed that iodine supplementation in iodine-deficient mothers before pregnancy or during early pregnancy improved the motor and cognitive performance of their offspring. Zimmerman et al (2006) reported that iodine repletion with 400 mg I (as oral iodized oil) to moderately iodine- deficient school children in rural south eastern Albania improved information processing, fine motor skills, and visual problem solving abilities.
Gordon et al (2009) also conducted a similar randomized placebo controlled double blind trial on mildly iodine-deficient children and demonstrated improved perceptual reasoning through 4 subtests from the Wechsler Intelligence Scale for Children by supplying 150µg for 28 weeks. Iodine supplementation improved perceptual reasoning in mildly iodine- deficient children. Selenium deficiency superimposed by iodine deficiency partly prevents the neurological damage. Iodine prophylaxis given before or during pregnancy has resulted in improved cognitive functioning in offspring in Ecuador.
Factor # 6. Iron:
Iron deficiency affects cognitive functions, specifically short-term memory, attention and visual motor coordination in anaemic children as compared to normal healthy children. Bandhu et al. (2011) demonstrated that the hematological status is associated with some effects on cognition.
Iron is a co-factor of tyrosine hydroxylase which is a critical enzyme in dopamine synthesis. Dopamine has been implicated in the pathophysiology of ADHD. Large- scale cross-sectional field study suggested that lower ferritin level might be associated with parent-reported hyperactivity after controlling for important confounding factors.
Those teens who don’t get enough iron do poorly in school. Children and adults who are deficient, suffer from decreased attention spans. Treatment of the school children with iron sulfate for 12 months improved the scores and time required in a visual attention test. Also there was a favorable change in the scores obtained by one the subtests of the Wechsler Intelligence Scale for Children (WISC) Test.
Iron therapy resulted in significant improvements in Mental Development Index which was associated with improvement in attention span and cooperativeness among 15 months old young children. Similarly, in pregnant women aged 14-24 years also iron supplementation significantly improved short-term memory and attention span.
In a recent longitudinal study, multiple micronutrient supplementation but not iron and folic acid supplementation alone to pregnant under-nourished or anemic women has been found to improve the motor and cognitive abilities of their children up to 3.5 years later, particularly both motor function and visual attention/spatial ability.
Factor # 7. Water:
Adequate hydration is essential for human homeostasis and survival, including maintenance of brain function. Since the brain is 80 per cent water it is imperative that the brain is kept hydrated. Even a slight dehydration in the brain can raise the stress hormone in a person affecting clarity of thought. Just 2 per cent dehydration impairs performance in tasks that require attention, psychomotor, and immediate memory skills, as well as assessment of the subjective state.
Factor # 8. Other Nutrients in Brain Function:
Inositol may improve symptoms of depression and mood disorders. Inositol and choline also assist in neurotransmitter function. These nerve impulses help with memory capacity. Supplementation of 12 g/day of inositol resulted in positive therapeutic improvements similar to common anti-depressant drugs, but without untoward side effects. Zinc is important for growth and maturation of the brain, and is especially related to behavior.
Sandstead (2012) found that subclinical zinc deficiency changes brain function. Simultaneous treatment with a broad mixture of other micronutrients and/or an adequate omnivorous diet appeared to enhance the efficacy of zinc. Dietary supplementation after traumatic brain injury, but not zinc injection, significantly improved (P < 0.05) cognitive behavior as measured by the Morris water maze test.
Further, zinc-supplemented offspring showed reversal of neuronal morphologic changes in the learning and memory ability. Phosphatidylcholine found in soy lecithin readily gets converted to acetylcholine. Oral co-intake with 1,2-dilynoleoyl-sn-glycero-3-phosphocholine (DLPhtCho) (50 mg) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPhtCho) (45 mg) once after breakfast everyday raised the Mini Mental State Examination score to over 20, corresponding to normal cognitive functions, throughout 5 months after intake, and the increase in the score was significantly greater than that for oral intake with DLPhtCho (100 mg/day) alone or POPhtCho (90 mg/kg) alone.
Factor # 9. Anti-Oxidants in Brain Function:
The free radical theory of ageing predicts that reactive oxygen species are involved in the decline in cognitive function associated with ageing. Bickford et al. (1999; 2000) reported that diets supplemented with nutritional sources of antioxidants, either spinach, strawberries or blueberries, reverse age-induced decline in beta-adrenergic receptor function in cerebellar Purkinje neurons. They have shown that age-related deficits in motor learning and memory can be reversed with antioxidant foods.
Similar observations were made by Gemma et al. (2002) as they found spirulina, with high Oxygen Radical Absorbance Capacity (ORAC) to reverse and apple (a food with intermediate ORAC) to have an intermediate effect and cucumber (low ORAC) to have no effect on cerebellar beta-adrenergic receptor physiology, indicating that the reversal of impaired beta-adrenergic receptor function might be related to the ORAC dose.
Factor # 10. Foods and Brain:
Traditionally food is believed to influence the cognitive abilities. Various foods were attributed a role in brain function e.g. Ladies finger is given the title “Maths vegetable”, Too much of sweet and/or Curds from buffalo milk consumption was considered to dull the brain and Vallarai (brahmi) was said to improve memory. Interestingly several of these beliefs were scientifically proved later. In addition, several foods that play a role in cognitive function of brain have also been researched extensively and documented.
Factor # 11. Fish:
The brain is made up of 60 per cent fat. Consuming foods rich in omega-3 fatty acids keeps cell membranes flexible and maximizes their ability to allow important nutrients get into the brain. Fatty fish and marine omega-3 consumption were associated with a reduced risk, while cholesterol and saturated fat with an increased risk of impaired cognitive function in the middle-aged population. According to Kesse-Guyot (2011) cognitive complaints, an early indicator of cognitive decline, are less frequent among the elderly who have a high long-chain n- 3 fatty acid intake.
A consistent finding across studies is that higher intake of fish is related to less cognitive decline and incidence of dementia in prospective studies, and associated with better cognitive performance in non-clinical samples, in cross-sectional analyses. Oily fish (eg. mackerel, herring, trout), are the major dietary sources of EPA and DHA. Morris et al. (2003), Kalmijn et al. (2004); van Gelder et al (2007) found significant positive relationship between cognitive outcomes and dietary intake levels of n-3 LC PUFAs.
Vinot et al. (2011) observed that ω3-supplemented animals exhibited not only lower anxiety level (significant reduction in spontaneous loco-motor activity by 31 per cent, (p < 0.001), compared to control animals, but also better performances in a reference spatial memory task (80 per cent of successful trials vs. 35 per cent in controls, p < 0.05). Thus they showed that the long-term dietary ω3 PUFA supplementation positively impacts the anxiety and cognitive performances in adult mouse lemur.
Hence, supplementation of human food with ω3 fatty acids may represent a valuable dietary strategy to improve behavioral and cognitive functions. Yellow fin Tuna, a cold-water fish, is a rich source of omega-3 fatty acids as well as the B vitamin niacin, which protects the brain against Alzheimer’s disease.
Supplementation with 1 or 2 g of fish oil brought out significant increase in oxy-hemoglobin and hemoglobin indicating increased cerebral blood flow during the cognitive tasks as compared to placebo. According to Denny Joseph and Muralidhara (2012) the prophylactic protection offered by fish oil may be due to its ability to enhance GSH levels, anti-oxidant potential that offset protein oxidation and specific modulatory effects on brain mitochondria.