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MICRONUTRIENTS in MENTAL HEALTHMental HealthThe World Health Organization (WHO) has aptly defined mental health as…a state of well-being, realizing potential, coping with stresses, working productively and fruitfully, and contributing to community and the brain is the organ that makes that all possible. Hundreds of thousands of chemical reactions occur every second in the brain and those reactions underlie the thoughts, actions, and behaviors with which we respond to the stimuli in our environment. Amazingly, the brain makes up only two percent of our body mass, yet it consumes one fifth of the oxygen and energy we take in. That is an incredible amount of chemical nutrients that your brain will need in order to function. Changes in the brain’s activity can result in long- or short-term changes to our responses of feeling, behavior, and thought. Not surprising, a mental illness is a health condition where brain activity has changed. These changes in a person’s thinking, feeling, or behavior (or all three), causes a person significant distress and difficulty in functioning. Several micronutrient-related factors may be associated with increased risk of psychiatric illness, and micronutrients play essential roles in an array of brain functions that have been implicated in mood lability. Micronutrient inadequacy may impair one or more of these critical brain functions and result in psychiatric symptoms. Micronutrients We have come to learn that a healthy diet satisfies three physiological needs.
Macronutrients typically provide calories or energy but are also needed for other body functions. “Macro” is a prefix from the Greek “makros” meaning large, and applies to this group of nutrients because they are needed in relatively large quantities. There are three groups of macronutrients:
Environmental and Genetic Pressures on Nutrient-Related Brain Functions Gastrointestinal tract disruption may deprive the brain of essential nutrients for key metabolic pathways, resulting in psychiatric symptoms. Gastrointestinal tract disruptions and psychiatric disorders show remarkably high comorbidity. For example, most studies that have investigated the comorbidity of irritable bowel syndrome and psychiatric disorders show prevalence of psychiatric disorders in irritable bowel syndrome patients to be 90% or greater. Genetic micronutrient requirements. Research is uncovering major genetic risk factors in psychiatric illness. Up to one-third of gene mutations result in decreased enzyme binding affinity for corresponding coenzymes, including vitamins and minerals. As a result, individuals with certain genotypes may have significantly higher requirements for essential micronutrients in key mood-related brain pathways. , , Low micronutrient intake may contribute to psychiatric illness. , , Intake of many micronutrients is inadequate in the United States, as shown in Figure 1. RDA levels are deemed to be “sufficient to meet the dietary requirements of nearly all (97 to 98 percent) of healthy individuals”, but do not ensure mental health for at-risk sub-populations: “intake at the level of the RDA or AI would not necessarily be expected to replete individuals previously undernourished, nor would it be adequate for disease states marked by increased requirements.”  Synthesis of neurotransmitters. Many neurotransmitters require micronutrient cofactors in their synthesis. Iron and copper have roles in serotonin and dopamine synthesis. , Folic acid and vitamin B12 are involved as cofactors in serotonin and norepinephrine synthesis. Thiamine serves as a coenzyme in acetylcholine, GABA, and glutamate synthesis. Vitamin B6 serves as a cofactor in the synthesis of the neurotransmitters dopamine, serotonin, norepinephrine, epinephrine, histamine, and GABA, and vitamin B6 deficiency has been shown to reduce brain production of serotonin and GABA. Regulation of neurotransmission. Micronutrients play key roles in regulating neuronal transmission. Zinc is extensively involved in synaptic transmission, , both excitatory and inhibitory. In certain brain regions, vesicular zinc is co-localized and co-released with glutamate, modulating the function of a number of channels, receptors, and transporters, , including NMDA receptors. Magnesium and copper are important modulators of NMDA-receptor activity, which has been implicated in the pathogenesis of mood disorders. , Methylation. Hypomethylation has been reported as a major risk factor for schizophrenia and bipolar disorder. Hundreds of methylation reactions occur in the body, including during DNA, RNA, and neurotransmitter synthesis. The neuropsychiatric effects of folate and vitamin B12 deficiencies result from defective methylation processes. , Folate is a precursor to S-adenosyl-L-methionine (SAMe), a methyl donor that has been shown to have antidepressant properties. Choline is also a major source of methyl groups for methylation reactions, and has been reported to improve symptoms of patients being treated with lithium. Prevention of genetic damage. Deficiency of folic acid, niacin, vitamin B6, vitamin B12, vitamin C, vitamin E, iron, or zinc (one or more of which is seen in half the US population ) have been shown to mimic radiation in causing single and double-strand DNA breaks, which could decrease enzyme affinity for nutrient cofactors. , Folate deficiency of a magnitude seen in 10% of the US population breaks chromosomes by causing massive misincorporation of uracil into human DNA.39 In addition, various vitamin and mineral deficiencies have been shown to accelerate mitochondrial decay, leading to DNA damage. Gene expression. Various micronutrients are involved in gene expression. Folate plays an essential role in methylation, which is involved in gene expression, transcription, chromatin structure, genomic repair and genomic stability. Vitamin A and vitamin E have been reported to have roles in gene expression as well. , Vitamin D, zinc and calcium have been shown to be involved in brain-derived neurotrophic factor (BDNF) gene expression, an effect also seen in clinically effective antidepressants. , , , TrkB, a BDNF-activated receptor, has been shown to be activated by zinc and copper. , Neurite outgrowth. Several micronutrients have been shown to be involved in neurite outgrowth, which is critical in optimizing neural networks. Vitamin A is a precursor to retinoic acid, which is extensively involved in neurite outgrowth and axonal elongation. , Calcium plays critical roles in neurite outgrowth. , , Magnesium, selenium, and copper are also involved. , , The micronutrient-mood regulation mechanisms discussed in this review are not exhaustive, nor are they mutually exclusive; in fact, they may be complementary. For example, neurotransmitter production and regulation, key components of the monoamine or chemical imbalance hypothesis of mood disorders, may work in tandem with neurite outgrowth and gene expression of neurotrophic factors, elements of the network hypothesis; these hypotheses appear to be entirely complementary. |
