, Volume 48, Issue 8, pp 716–720 | Cite as

Effects of vitamin B12 on plasma melatonin rhythm in humans: Increased light sensitivity phase-advances the circadian clock?

  • K. Honma
  • M. Kohsaka
  • N. Fukuda
  • N. Morita
  • S. Honma
Research Articles


Vitamin B12 (methylcobalamine) was administered orally (3 mg/day) to 9 healthy subjects for 4 weeks. Nocturnal melatonin levels after exposure to bright light (ca. 2500 lx) were determined, as well as the levels of plasma melatonin over 24 h. The timing of sleep was also recorded. Vitamin B12 was given blind to the subjects and crossed over with placebo. We found that the 24-h melatlonin rhythm was significantly phase-advanced (1.1. h) in the vitamin B12 trial as compared with that in the placebo trial. In addition, the 24-h mean of plasma melatonin level was much lower in the vitamin B12 traial than with the placebo. Furthermore, the nocturnal melatonin levels during bright light exposure were significantly lower in the vitamin B12 trial than with the placebo. On the other hand, vitamin B12 did not affect the timing of sleep. These findings raise the possibility that vitamin B12 phase-advances the human circadian rhythm by increasing the light sensitivity of the circadian clock.

Key words

Circadian rhythm melatonin bright light vitamin B12 entrainment 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Kamgar-Parsi, B., Wehr, T. A., and Gillin, J. C., Sleep6 (1983) 257.PubMedGoogle Scholar
  2. 2.
    Okawa, M., Mishima, K., Nanami, T., Shimizu, T., Iijima, S., Hishikawa, Y., and Takahashi, K., Slepp13 (1990) 15.Google Scholar
  3. 3.
    Morita, N., Chiba, T., Wada, T., Sumi, M., Kohsaka, M., Fukuda, N., and Honma, K., Jap. J. Psychiat. Neurol.43 (1989) 806.Google Scholar
  4. 4.
    Weitzman, E. D., Czeisler, C. A., Coleman, R. M., Spielman, A. J., Zimmerman, J. C., and Dement, W., Archs gen. Psychiat.38 (1981) 737.Google Scholar
  5. 5.
    Kokkoris, C. P., Weitzman, E. D., Pollak, C. P., Spielman, A. J., Czeisler, C. A., and Bradlow, H., Sleep1 (1978) 177.PubMedGoogle Scholar
  6. 6.
    Tiefenauer, L. X., and Andres R. Y., J. immun. Meth.74 (1984) 293.CrossRefGoogle Scholar
  7. 7.
    Honma, K., and Hiroshige, T., Am. J. Physiol.235 (1978) R243.PubMedGoogle Scholar
  8. 8.
    Hiroshige, T., Honma, K., and Watanabe, K., J. Physiol.325 (1982) 493.PubMedGoogle Scholar
  9. 9.
    McIntyre, I. M., Norman, T. R., Burrows, G. D., and Armstrong, S. M., Life Sci.45 (1989) 327.CrossRefPubMedGoogle Scholar
  10. 10.
    Honma, K., Honma, S., and Wada, T., Experientia43 (1987) 1205.CrossRefPubMedGoogle Scholar
  11. 11.
    Broadway, J., Folkard, S., and Arendt, J., Neurosci. Lett.79 (1987) 185.CrossRefPubMedGoogle Scholar
  12. 12.
    Klein, D. C., Smoot, R., Weller, J. L., Higa, S., Markey, S. P., Greed, G. J., and Jacobowitz, D. M., Brain Res. Bull.10 (1983) 647.CrossRefPubMedGoogle Scholar
  13. 13.
    Rusak, B., and Bina, K. G., A. Rev. Neurosci.13 (1990) 387.CrossRefGoogle Scholar
  14. 14.
    Takahashi, J., DeCoursey, P. L., Bauman, L., and Menaker, M., Nature308 (1984) 186.CrossRefPubMedGoogle Scholar
  15. 15.
    Brainard, G. C., Lewy, A. L., Menaker, M., Fredrickson, R. H., Miller, L. S., Weleber, R. C., Casone, V., and Hudson, D., Ann. N. Y. Acad. Sci.453 (1985) 376.Google Scholar
  16. 16.
    Wever, R. A., in: The Circadian System of Man. Springer-Verlag, New York 1979.Google Scholar
  17. 17.
    Wever, R. A., J. biol. Rhythms4 (1989) 161.PubMedGoogle Scholar
  18. 18.
    Czeisler, C. A., Allan, J. S., Strogatz, S. H., Ronda, J. M., Sanchex, R., Rios, C. D., Freitag, W. O., Richardson, G. S., and Kronauer, R. E., Science133 (1986) 667.Google Scholar
  19. 19.
    Zatz, M., and Browsnstein, M. J., Science208 (1979) 358.Google Scholar
  20. 20.
    Zatz, M., and Herkenham, M. A., Brain Res.213 (1981) 234.CrossRefGoogle Scholar

Copyright information

© Birkhäuser Verlag Basel 1992

Authors and Affiliations

  • K. Honma
    • 1
  • M. Kohsaka
    • 2
  • N. Fukuda
    • 3
  • N. Morita
    • 2
  • S. Honma
    • 1
  1. 1.Department of PhysiologyHokkaido University School of MedicineSapporoJapan
  2. 2.Department of PsychiatryHokkaido University School of MedicineSapporoJapan
  3. 3.College of Medical TechnologyHokkaido UniversitySapporoJapan

Personalised recommendations