Neurotransmitter cofactor vitamins

Thiamin (vitamin B1)

Experimental and clinical results33 have shown thiamin to be an effective nutrient in protecting the adrenal gland from functional exhaustion secondary to surgery. Intramuscular injections of thiamin in a dose of 120 mg per day, starting a few days prior to surgery and 1.5–2 hours immediately prior to surgery, reduced the cortisol reaction, both before and at the height of the surgery. Continued administration of thiamin post-surgery prevented the usual post-surgery reduction in blood cortisol levels.

Niacinamide (vitamin B3)

Fatigue is closely related to a lack of sleep and short REM cycles. Niacinamide might be helpful for sleep enhancement. A small, 3-week study34 of six subjects with normal sleep patterns and two with insomnia used EEG, electromyograms, and electrooculograms to evaluate sleep patterns at baseline and after niacinamide treatment (500 mg twice daily for 1 week; 1000 mg twice daily in week 2; and 1000 mg three times daily in week 3). There was a significant increase in REM sleep in all normal-sleeping subjects (P=0.0002). The two subjects with moderate-to-severe insomnia experienced significant increases in REM sleep by the week 3 (p=0.001); awake time was also significantly decreased. Sleep efficiency in the two subjects with insomnia was 58.5% at baseline, dropped to 55.7% after 2 weeks, but was at 79.5% after 3 weeks. After withdrawing niacinamide, sleep efficiency dropped to 41.5%. As tryptophan can either be converted to melatonin, niacin, or serotonin, niacinamide may signal via feedback inhibition to decrease the activity of tryptophan pyrrolase (the enzyme that converts tryptophan to niacin). This would allow more tryptophan to be converted to 5-HTP and then to serotonin.

Pantethine/pantothenic acid (vitamin B5)

Evidence indicates adrenal cortex function is compromised in the event of a deficiency of vitamin B5 derivatives and metabolites. On the other hand, administration of pantethine (active vitamin B5) in a number of experimental animal models appeared to enhance adrenal cortex function. Administration of pantethine to humans with a variety of clinical conditions buffered the rise in urinary cortisol metabolites expected to occur secondary to a loading dose of ACTH, suggesting pantethine can down-regulate hyper-secretion of cortisol secondary to high stress conditions. Men receiving 10 g of pantothenic acid daily for 6 weeks had a less pronounced drop in white blood cell counts and vitamin C levels subsequent to cold-water immersion stress, compared with pre-supplementation values.

Pyridoxal 5’-phosphate (active vitamin B6)

P5P (the active form of vitamin B6) is a necessary cofactor for the formation of a number of enzymes important for neurotransmitter pathways associated with stress-like serotonin and niacin. Within the brain, glutamic acid is converted to GABA via the enzyme glutamate decarboxylase and its cofactor pyridoxal 5’-phosphate. GABA is metabolised by gamma-aminobutyrate transaminase, also a P5P-dependent enzyme, forming an intermediate metabolite succinate-semialdehyde. P5P is a cofactor in the conversion of 5-HTP to serotonin. It is important to know that conversion of L-tryptophan to 5-HTP (the rate-limiting step in serotonin synthesis) can be inhibited by stress, insulin resistance, magnesium or vitamin B6 deficiency, or increasing age. The decarboxylation of 5-HTP to serotonin is dependent on the presence of P5P. P5P is also a cofactor in the synthesis of DOPA to dopamine, in the pathway converting tyrosine to adrenaline and noradrenaline.

Methylcobalamin (vitamin B12)

Stress disrupts the circadian rhythmic secretion of cortisol. Methylcobalamin in conjunction with light helps to reset the circadian rhythm secondary to stress and its impact on cortisol. It does not impact total levels of cortisol, but evidence suggests it helps shift the cortisol secretion peak, and maintain the normal cortisol rhythm.

5-methyltetrahydrofolate (active folate)

Tetrahydrobiopterin BH4 is a nutrient cofactor essential for the formation of the monoamine neurotransmitters serotonin, dopamine, noradrenaline, and adrenaline. BH4 acts as a rate-limiting enzyme cofactor to the hydroxylase enzymes that metabolise tryptophan to 5-hydroxytryptophan, phenylalanine to tyrosine, and tyrosine to dopa. Folate helps in regenerating (BH4), which is highly susceptible to oxidation.

Ascorbic acid (vitamin C)

Ascorbic acid is another cofactor involved in monoamine neurotransmitter synthesis. It is also a cofactor and a stabiliser of BH4, so protects BH4 from oxidation as well as increasing the levels of BH4. Ascorbic acid can support adrenal function and decrease high cortisol levels. Administration of ascorbic acid improved the capacity of the adrenals to adapt to surgical stress by normalising cortisol and ACTH in patients with lung cancer. Ascorbic acid given orally (1 g three times per day) also buffered exogenous ACTH-induced increases in cortisol, although it had no significant effect on fasting cortisol levels.