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Abstract

Grant Number:	5R21AT002571-02
Project Title:	Effect of Vitamin B12 on the Human Circadian Pacemaker

PI Information:	Name	Email	Title
	DUFFY, JEANNE F.	jduffy@hms.harvard.edu

Abstract: DESCRIPTION (provided by applicant): Failure of circadian entrainment may result in a cyclically recurring sleep-wake disorder that affects a number of sighted individuals and more than half of totally blind people. The circadian periods of such patients is typically longer than average, resulting in the circadian pacemaker would be the treatment of choice in such patients. However, few substances have been shown to affect the period of the mammalian circadian pacemaker and none have been validated in humans. A series of detailed clinical reports have suggested that vitamin supplementation (vitamin B12) is an effective treatment for non-24-h sleep-wake disorder in sighted patients, allowing them to maintain stable sleep times. The mechanism by which vitamin B12 supplementation exerts this therapeutic action on sleep timing is unknown. Based on the data in those reports, we hypothesize that the mechanism by which vitamin B12 supplementation stabilizes the sleep-wake cycle of such patients is by shortening the intrinsic period of the circadian pacemaker. Moreover, by shortening circadian period, we hypothesize that vitamin B12 realigns the phase relationship between the circadian system and the timing of sleep, resulting in improved sleep quality at night and greater alertness during the day. We propose to test the vitamin B12's effects on circadian period in a placebo-controlled double-blind study in healthy subjects, using the forced desynchrony protocol to measure circadian period precisely. Preliminary results from this study will reveal whether the efficacy of vitamin B12 supplementation in treating this circadian rhythm sleep disorder is via a direct action on the human circadian pacemaker. This study will also add substantially to understanding the basic properties of the human circadian timing system, and to understanding the entrainment mechanisms by which the circadian system is synchronized to the solar day. This study is designed to collect preliminary data that should reveal the mechanism of action of a safe and inexpensive CAM treatment for a circadian rhythm sleep disorder suffered by more than half of all totally blind people and by sighted patients with non-24-h-sleep-wake disorder. Identification of a CAM therapy that alters this fundamental property of the circadian pacemaker could also prove to be beneficial to the larger group of patients with delayed sleep phase syndrome, and to the significant fraction of the population that suffers from sleep onset insomnia combined with difficulty waking in the morning.

Public Health Relevance:
This Public Health Relevance is not available.

Thesaurus Terms:
circadian rhythm, human therapy evaluation, pharmacokinetics, sleep disorder, vitamin B12, vitamin therapy
biomarker, body temperature, clinical trial, dietary supplement, drug screening /evaluation, melatonin, plasma, psychic activity level, sleep deprivation
alternative medicine, clinical research, human subject, nutrition related tag, personal log /diary, questionnaire, young adult human (21-34)

Institution:	BRIGHAM AND WOMEN'S HOSPITAL
	RESEARCH ADMINISTRATION
	BOSTON, MA 02115
Fiscal Year:	2006
Department:
Project Start:	01-FEB-2005
Project End:	31-JAN-2008
ICD:	NATIONAL CENTER FOR COMPLEMENTARY & ALTERNATIVE MEDICINE
IRG:	ZAT1

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