Abstract:
The term niacin is the generic name for the two compounds nicotinic acid and nicotinamide,
the major dietary precursors for two important coenzymes, nicotinamide adenine
dinucleotide (NAD) and its phosphorylated form, NADP. Niacin is important for the
maintenance of cellular integrity and energy production and is involved in more than 500
intracellular reactions. Deficiencies of niacin may contribute to neuropsychiatric and
neurodegenerative disorders. Patients who develop nutritional deficiencies as a result of
poor dietary intake, could potentially suffer from niacin deficiency and NAD depletion.
However, de novo synthesis of niacin and NAD in the kynurenine pathway of tryptophan
metabolism may compensate for impaired dietary intake. The rate of synthesis of NAD and
niacin from tryptophan oxidation depends on the induction of the enzyme indoleamine 2,3-
dioxygenase (IDO) by pro-inflammatory cytokines such as interferon-gamma. Niacin synthesis is not limited by a decrease in tryptophan and excessive IDO activity may
therefore lead to a decline in tryptophan levels. Antidepressants have an anti-inflammatory
effect, including reduction of interferon-gamma and therefore inhibition of IDO, the ratelimiting
enzyme of the kynurenine pathway. In theory, this could account for increased
serotonin as more tryptophan becomes available for serotonin synthesis. However, the
downside may be that less NAD and niacin are synthesised downstream, which could
exacerbate common psychiatric problems. It is our hypothesis that patients with poor
dietary intake, who are treated with antidepressants, are at risk of developing niacin/NAD
deficiency with possible development of associated neuropsychiatric symptoms.
We therefore propose that niacin supplementation be considered in patients with
inadequate diets who are treated with antidepressants. We believe that if this does not
happen, a subclinical niacin deficiency may result, which would be difficult to detect as it
would cause the same symptoms of the original illness (e.g. depression). Niacin deficiency
should be considered and ruled out in all patients with treatment-resistant depression, who
have a poor response to antidepressants. This is potentially a cost-effective and easy
intervention, which could be examined in a randomized controlled trial.
