Antidepressants may lead to a decrease in niacin and NAD in patients with poor dietary intake

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 2 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.

Identification of Genetic Variations in the NAD-Related Pathways for Patients with Major Depressive Disorder: A Case-Control Study in Taiwan

“…Our finding was in accordance with previous clinical studies which reported that antidepressants are associated with NAD deficiency, especially in patients with inadequate amino acid intake [58]. Thus, it is important to also consider how SSRI, SNRI, and tricyclic antidepressants may affect the NAD level and influence the immune system by regulating immune reactivity [59], altering cytokine responses [60], and inhibiting immune cells and the KP as a result of its anti-inflammatory effects [26,61]. However, we cannot clarify the combined effects from the genetic and pharmacology level; further studies are warranted.…”

“…Previous studies, including clinical trials and animal models, suggested the link between NAD deficiency and several psychiatric disorders, such as chronic schizophrenia [23], anxiety disorder [24], and bipolar disorder type II [25]. NAD deficiency is also linked to MDD patients treated with antidepressants [26]. However, it seems that there have been limited genetic studies focused on the link between NAD homeostasis and psychiatric disorders, especially MDD.…”

A Deficiência De Tiamina E Niacina Como Fator De Risco Para De Doenças Neurológicas

“…Fármacos antidepressivos têm efeito anti-inflamatório, incluindo a redução de interferon-gama e, portanto, a inibição de indolamina 2,3-dioxigenase (IDO), a enzima limitante da velocidade da via da quinurenina. Portanto, pacientes com dieta pobre em micronutrientes, tratados com antidepressivos, estão em risco de desenvolver deficiência de niacina NAD com possível desenvolvimento de sintomas neuropsiquiátricos associados (17).…”

Efficacy of GLOW™ on Alleviating Symptoms of Inattention, Hyperactivity/Impulsivity, Depression and Sexual Dysfunction; A Preliminary Study

“…In a 12-week double-blind study, reduced impulsiveness, hyperactivity, and social difficulties were seen in children supplemented with zinc sulfate (150mg). 30 Deficiencies of zinc and niacin levels have been seen in depressed patients, and hence dietary supplements of zinc and niacin could substantially improve symptoms of depression [52][53][54].…”