Micronutrients for Brain Health

24 Jun

Excellent article written by Victoria J Drake and reblogged from the Linus Pauling Institute at

Micronutrients and Cognitive Function


The brain requires a constant supply of micronutrients for energy metabolism of neurons and glial cells, neurotransmitter synthesis and action, nerve impulse propagation, and homocysteine metabolism. (More Information)
Deficiencies in various micronutrients, especially the B vitamins, have adverse effects on cognition. (More Information)
The developing brain may be particularly vulnerable to deficiencies in choline and essential fatty acids. (More Information)
Due to conflicting studies, more research in needed to determine whether micronutrient supplementation affects attention-related cognitive functions. (More Information)
Presently, there is little evidence that supplementation with B vitamins, antioxidant vitamins, choline, or omega-3 fatty acids will improve memory performance. (More Information)
More research is needed to determine whether micronutrient supplementation has any effects on executive functioning (i.e., higher-order cognitive processes). (More Information)
Some, but not all, studies have reported that micronutrient supplementation improves overall mood and psychological well-being. (More Information)
It is not yet clear whether supplementation with B vitamins, antioxidants, or omega-3 fatty acids protects against age-related cognitive decline. (More Information)
Several methodological issues (e.g., tests used to assess cognition, choice of study population, nature of the supplementation, study duration, etc.) may have contributed to the conflicting results observed in intervention studies. (More Information)

Good nutritional status is important for proper brain development and maintenance of normal cognitive function (1). Through unique biological functions, various micronutrients affect brain function. This article discusses the roles of key micronutrients, including the B vitamins, antioxidant vitamins, and certain essential minerals, in cognitive function. When appropriate, research on the role of other compounds, such as essential fatty acids and choline, is also presented. The cognitive effects of micronutrient deficiencies are discussed, and the effects of micronutrient supplementation on the broad areas of attention, memory, executive functions, mood, as well as age-related cognitive decline are covered.

Basic Needs for Cognitive Performance

Energy Metabolism of Neurons and Glial Cells

The human brain is a highly metabolically active tissue that depends on a constant supply of glucose to meet its energy needs. In fact, the brain accounts for approximately 25% of total body glucose utilization at rest, despite representing only 2% of adult body weight (2, 3). Blood glucose levels must be maintained at all times to avoid hypoglycemia and to supply the brain with its preferential fuel. During the initial stages of fasting, blood glucose levels are maintained through the breakdown of liver glycogen and then through the process of gluconeogenesis—the production of glucose from non-carbohydrate precursors, such as amino acids. The B vitamin biotin is required for a key enzyme in the gluconeogenic pathway (4). While glucose is the obligatory fuel, ketone bodies can also be used by the brain when glucose supply is inadequate, such as during prolonged fasting or starvation. However, ketone bodies are acidic, and very high levels of these compounds in the blood are toxic and may result in ketoacidosis (5). Thus, glucose is the preferred and normal energy substrate of the brain.

Glucose oxidation in the brain requires certain micronutrients as cofactors. For instance, forms of several B vitamins, including thiamin, riboflavin, niacin, and pantothenic acid, as well as the compound lipoic acid, are utilized in reactions that completely metabolize glucose to carbon dioxide and water (3). Additionally, the nutritionally essential minerals, magnesium, iron, and manganese are required for the complete metabolism of glucose; these micronutrients are utilized as cofactors, substrates, or components of enzymes in glycolysis and the citric acid cycle (6, 7). Moreover, generation of cellular energy in the form of ATP by the electron transport chain requires the vitamins, riboflavin and niacin; iron contained in iron-sulfur clusters; and the endogenously synthesized compound, coenzyme Q10 (8).

Cerebral Blood Supply

At rest, the brain receives approximately 15% of cardiac output (9). Proper cerebral blood supply is necessary to deliver oxygen, glucose and other macronutrients, and the required micronutrients for proper cognitive function. Nutrition has a role in maintaining optimal blood supply to the brain. For instance, insufficiency of several dietary components increases the risk of developing stroke, a pathological condition that results from impaired cerebral blood supply; see the Disease Index for examples.

Neurotransmitter Synthesis

A neurotransmitter is a chemical released from a nerve cell that transmits an impulse to another nerve cell or an effector cell, such as a muscle cell. Neurotransmitters have either excitatory or inhibitory effects; the type of effect is dependent on the receptor on the receiving cell (10). Neurotransmitters can be broadly divided into two main classes: small amino acids (e.g., gamma aminobutyric acid [GABA], glutamate, aspartate, and glycine) and biogenic amines (e.g., dopamine, epinephrine, norepinephrine, serotonin, histamine, and acetylcholine) (11).

In addition to various amino acids, several B vitamins, including thiamin, riboflavin, niacin, vitamin B6, folate, and vitamin B12, are needed as cofactors for the synthesis of neurotransmitters. Moreover, vitamin C is required for synthesis of norepinephrine (3), and the mineral zinc is important for proper function of GABA, aspartate, and norepinephrine (12). Further, choline is a precursor for the neurotransmitter acetylcholine (13).

Neurotransmitter Binding to Receptors

Neurotransmitters function by binding to receptors on the cell membrane of the neuron releasing the neurotransmitter (i.e., presynaptic neuron) or to receptors on the cell membrane of the receiving cell (i.e., the postsynaptic neuron). Receptor binding can either mediate the opening of ion channels or cause metabolic changes within the cell (3, 14). Specifically, direct action on ion channels results from neurotransmitter binding to receptor sites on the membrane of postsynaptic neurons. This binding causes the gate-like ion channels to open, which allows ions to flow into the cell (10). Influx of positively charged ions into the postsynaptic neuron can have excitatory effects by depolarizing the membrane; membrane depolarization can cause a nerve impulse or action potential if a certain threshold is reached within the neuron. This is commonly referred to as “neuronal firing.” In contrast, influx of negatively charged ions can have inhibitory effects by hyperpolarizing the membrane and thus preventing neuronal firing (15). In addition to direct effects on ion channels, neurotransmitters may bind to G-protein coupled receptors, thereby eliciting cell-signaling effects that could result in metabolic changes (e.g., alterations in activity of various enzymes) within a postsynaptic cell (14).

Vitamins could possibly influence binding of neurotransmitters to postsynaptic receptors. For instance, an in vitro study showed that two forms of vitamin B6, pyridoxal and pyridoxal phosphate, inhibited the binding of GABA to postsynaptic receptors (16). Also, a rat study associated vitamin B6 deficiency during fetal development and lactation with changes in the number and binding of dopamine receptors (17).

Nerve Impulse Propagation

The speed at which nerve impulses (action potentials) are propagated is influenced by the myelination of the nerve (18). Myelination refers to the process in which nerves acquire a myelin sheath—the insulating layer of tissue made up of lipids and proteins that surrounds nerve fibers. This sheath acts as a conduit in an electrical system, allowing rapid and efficient transmission of nerve impulses (10).

Certain micronutrients can affect the propagation of nerve impulses. In particular, adequate intake of both folate and vitamin B12 is important in maintaining the integrity of the myelin sheath, and thiamin is needed for maintenance of the nerve’s membrane potential and for proper nerve conductance (3). Additionally, iron has an important role in the development of oligodendrocytes, the cells in the brain that produce myelin (19).

Homocysteine Metabolism

Homocysteine is a sulfur-containing amino acid that is an intermediate in the metabolism of another sulfur-containing amino acid, methionine. Elevated homocysteine levels in the blood (i.e., hyperhomocysteinemia) may be a risk factor for cardiovascular diseases and could also be linked to dementia and Alzheimer’s disease (20, 21). The amount of homocysteine in the blood is regulated by at least three vitamins: folate, vitamin B6, and vitamin B12 (see diagram). Additionally, the nutrient choline is also involved in homocysteine metabolism. The choline metabolite, betaine, can also provide a methyl group for the conversion of homocysteine to methionine.


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