NEUROENDOCRINOLOGY LETTERS
including Psychoneuroimmunology, Neuropsychopharmacology,
Reproductive Medicine, Chronobiology and Human Ethology
ISSN 0172–780X

NEL Vol.23 No.3, June 2002

INVITED NEL REVIEW
Pyridoxine and melatonin secretion

2002; 23:213–217
pii: NEL230302A02
PMID: 12080281

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The effect of pyridoxine administration on melatonin secretion in normal men

1. Rafael Luboshitzky
2. Ophir U
3. Rachel Nave
3. Rachel Epstein
2. Zila Shen-Orr
3. Paula Herer

1. Endocrine Institute, Haemek Medical Center, Afula, ISRAEL
2. Endocrine Laboratory, Rambam Medical center, Haifa, ISRAEL
3. Sleep research Laboratory, Technion, Israel Institute of Technology, Haifa, ISRAEL

Keywords:
melatonin; core body temperature; sleep; pyridoxine

Abstract

OBJECTIVES: To determine pineal response to pyridoxine in normal men.

MATERIAL AND METHODS: Twelve healthy men were given orally pyridoxine (100 mg) or placebo at 1700h.Serum melatonin levels were determined every 30 minutes with simultaneous measurement of core body temperature between 1700h to 0300h.Polysomnographic sleep recordings were performed between 1800h to 200h.

RESULTS: Serum melatonin levels after both placebo and pyridoxine showed a nocturnal rise occurring at 22:10±1:22h and 22:24±1:09h,respectively. The melatonin onset, peak, mean and area under the curve (AUC) values after pyridoxine (3.2±1.6 pg/ml, 47.2±22.6 pg/ml, 31.5±11.0 pg/ml and 173.5 ± 138.4 pg/ml x min, respectively) were similar to the values after placebo administration (4.7± 1.6 pg/ml, 53.9± 26.0 pg/ml, 37.2± 2.8 pg/ml and 205.3± 137.8 pg/ml x min, respectively). CBT revealed a significant nocturnal decline but without significant difference between pyridoxine and placebo. Sleep amount and architecture were similar after the two treatments.

CONCLUSIONS: In adult man, the oral administration of 100 mg-pyridoxine during the evening hours has no effect on melatonin secretion nor does it alter CBT or sleep quality.

Introduction

Melatonin, the main hormone produced by the pineal gland, displays a circadian rhythm peaking at night (1). Pinealocytes uses tryptophan as substrate for melatonin synthesis, and melatonin levels change as a function of tryptophan availability (2). Pyridoxine is converted to its active coenzyme form, pyridoxal phosphate (PLP). More than 60 PLP-dependent enzymes are known, including enzymes that participate in decarboxylation reactions such as the decarboxylation of DOPA to dopamine and 5-hydroxytryptophan to serotonin (3-4). The activity of pyridoxine as a coenzyme in the tryptophan metabolism was described in the kinurenine and methoxyindole pathways (5). Pyridoxine acts as a coenzyme of 5-hydroxytryptophan decarboxylase. The enzyme carboxylates 5-hydroxytryptophan to serotonin, the immediate precursor of melatonin (5). The effect of pyridoxine on aromatic amino acid decarboxylase activity supports a regulatory role of pyridoxine on the synthesis of neurotransmitters (6-7). Melatonin was shown to increase brain pyridoxal phosphokinase activity, inhibition of glutaminergic neurotransmission, resulting in inhibitory effects on central nervous system activity (8). The participation of endogenous melatonin in the normal sleep-wake cycle regulation has been inferred from the temporal relationships between melatonin cycle and the 24-hour cycle in sleep propensity, and particularly between the nocturnal melatonin onset and the nocturnal sleep gate (9-11). The typical 24- hour sleep propensity pattern reveals a midafternoon sleepiness peak followed by a forbidden zone for sleep, which is characterized by very low sleep propensity in the early evening hours and then followed by the nocturnal sleep gate. This term refers to a steep rise in sleepiness occurring in the late evening hours (12). Exogenous melatonin given prior to an early evening nap, during the forbidden zone for sleep at 1800-2000h,significantly shortened sleep latency and increased total sleep time. These data suggested that timed administered melatonin can modify sleep propensity (13).
Exogenous melatonin administration has been shown to lower core body temperature (CBT) by 0.2-0.4 Co (14-17). Acute exposure to bright light at night elevated the nocturnal CBT and inhibits melatonin secretion (18). This change in CBT was reversed by a constant infusion of melatonin (19). The time taken to reach the maximum drop in CBT following melatonin administration was about 3 hours (17).
We hypothesized that pyridoxine may participate in the nocturnal melatonin secretion and therefor can modify other circadian rhythms as sleep and temperature when administered in the late afternoon hours. To examine this hypothesis, we determined serum melatonin levels, CBT and sleep quality in healthy young adult men given a single oral dose of pyridoxine or placebo in the evening hours.

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