The Nutritional Neurotrophic Neoteny Theory: Evolutionary Interactions Among Diet, Brain, and Behavior

  • Nūn Sava-Siva Amen-Ra


The intent of this theoretical exposition is to explain the evolutionary antecedents of human encephalization and intelligence. The expansion of the brain over the course of human evolution is herein regarded as one of several components of an interrelated complex including protracted physical development, reduced reproductive receptivity, and increased longevity. These cardinal phenotypic features, herein referred to as the Quadripartite Complex, were ostensibly selected for their adaptiveness amidst the environmental alteration that ensued during the formative phase of human evolution – the Plio-Pleistocene period. This interval of environmental alteration eventuated in ecological upheaval and dietary diminution. Intriguingly, experimentally imposed dietary restriction routinely results in protracted physical development, reduced reproductive receptivity, increased longevity, and proportionately increased brain size relative to body size. Thus, dietary restriction would seem to induce identical adaptations, whether experienced ontogenetically or evolutionarily. Several experiments have determined that dietary restriction promotes the preservation and production of neurons via induction of neurotrophic factors. Inasmuch as neurogenesis is a molecular mediator of mental acuity, it is evident that energy intake and cognition are intimately intertwined. Extrapolating to an evolutionary context, increased intelligence ought logically to confer advantages to organisms enduring dietary deprivation insofar as increased intelligence should ensure more facile food acquisition. This reasoning underlies the nutritional neurotrophic neoteny (N3) theory, which holds that humans exhibit an altered pattern of neurotrophin expression resulting from positive selection for heightened intelligence amidst environmental alteration and consequent dietary deficiency. The altered pattern of neurotrophin expression exhibited by humans, it is deduced, results in a protracted phase of developmental neurogenesis and a resultant retention of neurons that would otherwise be extirpated due to programmed cell death. Importantly, during neonatal neurogenesis mammals produce an excess number of neurons whose survival or destruction is decisively determined by the availability and action of neurotrophic factors. An altered pattern of neurotrophin expression during neurogenesis (as N3 avows) could therefore furnish a larger adult brain. As to how humans could afford to accrete exorbitant neural tissue under conditions of chronic food scarcity the homo hypothalamic hypometabolic (H3) theory offers a plausible postulate: reduced rates of growth and reduced reproductive receptivity, mediated by the hypothalamus and its associated endocrine effectors, offset the energetic costs of increased encephalization in humans. H3 is herein presented as a general theory of human evolution while N3 may be regarded as a special theory of human encephalization and intelligence.


Caloric Restriction Dietary Restriction Cyclic Fasting Neurotrophin Expression Improve Diet Quality 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Amen optimal health protocol


Adenosine triphosphate


Brain-derived neurotrophic factor


Cyclic adenosine monophosphate (cAMP) response element-binding protein


Expensive tissue hypothesis


Homo hypothalamic hypometabolic


Nutritional neurotrophic neoteny


  1. Aiello LC, Wheeler P. Curr Anthropol. 1995;36:199–221.CrossRefGoogle Scholar
  2. Amen-Ra N. Evolutionary nutrition. Damascus: Amenta Press; 2003.Google Scholar
  3. Amen-Ra N. Med Hypotheses. 2006;66:978–84.PubMedCrossRefGoogle Scholar
  4. Amen-Ra N. The optimal human diet: theoretical foundations of the Amen Protocol. In: Willis AP, editor. Dietary therapy research trends. New York: Nova Science; 2007.Google Scholar
  5. Blanc S, Schoeller D, Kemnitz J, Weindruch R, Colman R, Newton W, et al. J Clin Endocrinol Metab. 2003;88:16–23.PubMedCrossRefGoogle Scholar
  6. Bodoky G, Yang ZJ, Meguid MM, Laviano A, Szeverenyi N. Physiol Behav. 1995;58:521–7.PubMedCrossRefGoogle Scholar
  7. Burkhalter J, Fiumelli H, Allman I, Chatton JY, Martin JL. J Neurosci. 2003;23:8212–20.PubMedGoogle Scholar
  8. Casirola DM, Rifkin B, Tsai W, Ferraris RP. Am J Physiol. 1996;271:G192–200.PubMedGoogle Scholar
  9. Casirola DM, Lan Y, Ferraris RP. J Gerontol. 1997;A 52:B300–10.Google Scholar
  10. Chappell VL, Thompson MD, Jeschke MG, Chung DH, Thompson JC, Wolf SE. Dig Dis Sci. 2003;48:765–9.PubMedCrossRefGoogle Scholar
  11. Deslandes A, Moraes H, Ferreira C, Veiga H, Silveira H, Mouta R, et al. Neuropsychobiology. 2009;59:191–8.PubMedCrossRefGoogle Scholar
  12. Diano S, Farr SA, Benoit SC, McNay EC, da Silva I, Horvath B, et al. Nat Neurosci. 2006;9:381–8.PubMedCrossRefGoogle Scholar
  13. Duan W, Guo Z, Mattson MP. J Neurochem. 2001;76:619–26.PubMedCrossRefGoogle Scholar
  14. Duman CH, Schlesinger L, Russell DS, Duman RS. Brain Res. 2008;1199:148–58.PubMedCrossRefGoogle Scholar
  15. Dworkin S, Malaterre J, Hollande F, Darcy PK, Ramsay RG, Mantamadiotis T. Stem Cells. 2009;27:1347–57.PubMedCrossRefGoogle Scholar
  16. Fontán-Lozano A, Sáez-Cassanelli Jl, Inda MC, de los Santos-Arteaga M, Sierra-Domínguez SA, López-Lluch G, et al. J Neurosci. 2007;27:10185–95.PubMedCrossRefGoogle Scholar
  17. Greenberg JA, Boozer CN. Mech Ageing Dev. 2000;113:37–48.PubMedCrossRefGoogle Scholar
  18. Guyton AC, Hall JE. Textbook of medical physiology. Philadelphia: Elsevier; 2006.Google Scholar
  19. Halagappa VK, Guo Z, Pearson M, Matsuoka Y, Cutler RG, Laferla FM, et al. Neurobiol Dis. 2007;26:212–20.PubMedCrossRefGoogle Scholar
  20. Heilbronn LK, de Jonge L, Frisard MI, Delany JP, Larson-Meyer DE, Rood J, et al. JAMA. 2006;295:1539–48.PubMedCrossRefGoogle Scholar
  21. Jagasia R, Steib K, Englberger E, Herold S, Faus-Kessler T, Saxe M, et al. J Neurosci. 2009;29:7966–77.PubMedCrossRefGoogle Scholar
  22. Kandel ER, Schwartz JH, Jessell TM, editors. Principles of neural science. New York: McGraw-Hill; 2000.Google Scholar
  23. Lee J, Duan W, Long JM, Ingram DK, Mattson MP. J Mol Neurosci. 2000;15:99–108.PubMedCrossRefGoogle Scholar
  24. Lee J, Duan W, Mattson MP. J Neurochem. 2002a;82:1367–75.PubMedCrossRefGoogle Scholar
  25. Lee J, Seroogy KB, Mattson MP. J Neurochem. 2002b;80:539–47.PubMedCrossRefGoogle Scholar
  26. Li Q, Zhao H, Zhang Z, Liu Z, Pei X, Wang J, Li Y. Neuroscience. 2009; Jul 10; 163(3):741–9.Google Scholar
  27. Lopez-Lluch G, Hunt N, Jones B, Zhu M, Jamieson H, Hilmer S, et al. Proc Natl Acad Sci USA. 2006;103:1768–73.PubMedCrossRefGoogle Scholar
  28. Mattison JA, Roth GS, Lane MA, Ingram DK. Interdiscip Top Gerontol. 2007;35:137–58.PubMedGoogle Scholar
  29. Mattson MP, Duan W, Wan R, Guo Z. NeuroRx. 2004;1:111–6.PubMedCrossRefGoogle Scholar
  30. Oftedal OT. Philos Trans R Soc Lond B. 1991;334:161–70.CrossRefGoogle Scholar
  31. Sanz A, Caro P, Ibanez J, Gomez J, Gredilla R, Barja G. J Bioenerg Biomembr. 2005;37:83–90.PubMedCrossRefGoogle Scholar
  32. Stanley M. Extinction. New York: Scientific American Books; 1987.Google Scholar
  33. Wang T, Hung CC, Randall DJ. Annu Rev Physiol. 2006;68:223–51.PubMedCrossRefGoogle Scholar
  34. Zaloga GP, Ward KA, Prielipp RC. JPEN J Parenter Enteral Nutr. 1991;15:42–7.PubMedCrossRefGoogle Scholar
  35. Zhao H, Li Q, Pei X, Zhang Z, Yang R, Wang J, et al. Behav Brain Res. 2009;201:311–7.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Amenta Academy of Theoretical Sciences (AATS)DamascusUSA

Personalised recommendations