WJNS  Vol.3 No.4 , November 2013
Review of literature: Role of 5-aminolevulinic acid and sleep

Objective: To determine if current peer-reviewed literature supports the existence of a relationship between the administration of dietary supplements containing 5-Aminolevulinic Acid (5-ALA) and sleep. Methods: Conceptual analysis of a systematically defined group of data is based on publications in referred journals. Constant comparative analyses were used to analyze the data. Detailed analyses were used to identify trends that led to qualifying relationships between the use of 5-ALA and heme. In addition, the relationship among heme, melatonin, and sleep were explored. Since there were no published data related to 5-ALA and sleep, an analysis of what is known about 5-ALA and heme was undertaken. Results: Currently, within the scope of this review, no literature available directly connecting 5-ALA and sleep was found. Research indicates that 5-ALA has an indirect relationship with intra-cellular energy production, which could result in a wide range of effects fromcellular to endocrine to neurologic to behavioral. In addition, there is evidence that 5-ALA may influence tryptophan and serotonin levels. Conclusion: While there are no studies on 5-ALA and sleep were found, current research suggests several potential mechanisms by which 5-ALA could influence sleep. The mechanisms suggest the potential for 5-ALA to assist in the adjustment of a person’s circadian cycle, endocrine function, or neurologic function in order to allow for better sleep in a natural way. In doing so, it may provide for a safer alternative to currently available sleep medication. Further research is needed to explore this possibility.

Cite this paper
Perez, M. , Rodriguez, B. , Shintani, T. , Shintani, T. and Harrigan, R. (2013) Review of literature: Role of 5-aminolevulinic acid and sleep. World Journal of Neuroscience, 3, 307-312. doi: 10.4236/wjns.2013.34042.
[1]   (2006) Sleep disorders and sleep deprivation: An unmet public health problem. Institute of Medicine, National Academies Press, Washington DC.

[2]   Weitzman, E.D., et al. (1981) Delayed sleep phase syndrome. A chronobiological disorder with sleep-onset insomnia. Archives of General Psychiatry, 38, 737-746.

[3]   Carson, S., McDonagh, M.S., Thakurta, S., Yen, P.-Y. and Helfand, M. (2008) PharmD. Oregon Evidence-Based Practice Center, Oregon Health & Science University.

[4]   Beale, S. (1990) Biosynthesis of the tetrapyrrole pigment precursor, d-aminolevulinic acid, from glutamate. Plant Physiology 93, 1273-1279.

[5]   Glaser, B.G. and Strauss, A.L. (1967) The discovery of grounded theory. Aldine Publishing Company, Chicago.

[6]   Rodriguez, B.L., Curb, J.D., Davis, J., Shintani, T., Perez, M.H., Apau-Ludlum, N., et al. (2012) Use of the dietary supplement 5-aminiolevulinic acid (5-ALA) and its relationship with glucose levels and hemoglobin A1C among individuals with prediabetes. Clinical and Translational Science, 5, 314-320.

[7]   Schmidt-Dannert, C. (2003) High-level production of porphyrins in metabolically engineered Escherichia coli: Systematic extension of a pathway assembled from overexpressed genes involved in heme biosynthesis. Applied and Environmental Microbiology, 69, 4875-4883.

[8]   Morton, K.A., Kushner, P., Straka, J.G. and Burnham, B.F. (1983) Biosynthesis of 5-aminolevulinic acid and heme from 4,5-dioxovalerate in the rat. Journal of Clinical Investigation, 71, 1744-1749.

[9]   Ogura, S., Maruyama, K., Hagiya, Y., Sugiyama, Y., Tsuchiya, K., Takahashi, K., Abe, F., Tabata, K., Okura, I., Nakajima, M., et al. (2011) The effect of 5-Aminolevulinic acid on cytochrome coxidase activity in mouse liver. BMC Research Notes, 4, 66.

[10]   Gaspar, T., Kevers, C., Bisbis, B., Penel, C., Greppin, H., Garnier, F., Rideau, M., Huault, C., Billard, J.P. and Foidart, J.M. (1999) Shemin pathway and peroxidase deficiency in a fully habituated and fully heterotrophic nonorganogenic sugarbeet callus: An adaptative strategy or the consequence of modified hormonal balances and sensitivities in these cancerous cells? Cell Proliferation, 32, 249-270.

[11]   Willows, R. (2004) Chlorophylls. In: Goodman, R.M., Ed., Encyclopedia of Plant and Crop Science. Marcel Dekker Inc., New York, 258-262.

[12]   Stummer, W., et al. (2006) Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: A randomised controlled multicentre phase III trial. Lancet Oncology, 7, 392-401.

[13]   Duvall, L.B. and Taghert, P.H. (2011) Circadian rhythms: Biological clocks work in phospho-time. Current Biology, 21, R305-R307.

[14]   Morin, C.M. and Benca, R. (2012) Chronic insomnia. Lancet, 379, 1129-1141.

[15]   Pandi-Perumal, S.R., et al. (2007) Dim light melatonin onset (DLMO): A tool for the analysis of circadian phase in human sleep and chronobiological disorders. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 31, 1-11. http://dx.doi.org/10.1016/j.pnpbp.2006.06.020

[16]   Canavier, C. (2006) Phase response curve. Scholarpedia, 1, 1332. http://dx.doi.org/10.4249/scholarpedia.1332

[17]   Sack, R.L., Auckley, D., Auger, R.R., Carskadon, M.A., Wright Jr., K.P., Vitiello, M.V. and Zhdanova, I.V. (2007) An American academy of sleep medicine review. Sleep, 30, 1484-1501.

[18]   American Psychiatric Association (2012) DSM-5, All rights reserved?2012.

[19]   Roth, T. (2007) Insomnia: Definition, prevalence, etiology, and consequences. Journal of Clinical Sleep Medicine, 3, S7-S10.

[20]   Do, M.T. and Yau, K.W. (2010) Intrinsically photosensitive retinal ganglion cells. Physiological Reviews, 90, 1547-1581. http://dx.doi.org/10.1152/physrev.00013.2010

[21]   Lockley, S.W. (2009) Circadian rhythms: Influence of light in humans. In: Larry, R.S., Ed., Encyclopedia of Neuroscience, Academic Press, Oxford, 971-988.

[22]   Monti, J.M., Pandi-Perumal, S.R., Jacobs, B.L. and Nutt, D.J. (2008) Serotonin and sleep: Molecular, functional and clinical aspects. Springer, Berlin.

[23]   Daya, S., Nonaka, K.O. and Reiter, R.J. (1990) Melatonin counteracts the 5-aminolevulinic acidinduced rise of rat forebrain tryptophan and serotonin concentrations at night. Neuroscience Letters, 114, 116.

[24]   Lewy, A.J., Bauer, V.K., Ahmed, S., Thomas, K.H., Cutler, N.L., Singer, C.M., et al. (1998) The human phase response curve (PRC) to melatonin is about 12 h out of phase with the PRC to light. Chronobiology International, 15, 71-83. http://dx.doi.org/10.3109/07420529808998671

[25]   Khalsa, S.B., et al. (2003) A phase response curve to single bright light pulses in human subjects. The Journal of Physiology, 549, 945-952.

[26]   Zee, P.C. and Manthena, P. (2007) The brain’s master circadian clock: Implications and opportunities for therapy of sleep disorders. Sleep Medicine Reviews, 11, 59-70.