, Volume 27, Issue 1, pp 17–25 | Cite as

The diet restriction paradigm: a brief review of the effects of every-other-day feeding

  • R. Michael Anson
  • Bruce Jones
  • Rafael de CabodEmail author
Review article


It has been known since the early 1900s that restriction of dietary intake relative to the ad libitum (AL) level increases stress resistance, cancer resistance, and longevity in many species. Studies investigating these phenomena have used three paradigms for dietary restriction. In the first, the AL intake of a control group is measured, and an experimental group is fed less than that amount in a specified proportion, e.g., 40%. In the second, food is provided AL to both the control and experimental groups: however, the experimental group is subjected to periods of fasting. Recent studies using this paradigm provide food every other day (EOD). Both of these paradigms have been in use since the early 1900s. A third paradigm that combines them was developed in the early 1970s: one or more days of fasting separate the provision of a limited amount of food. It was assumed for many years that the physiological responses to these paradigms were due exclusively to a net decrease in energy intake. Recently, however, it was found that some species and strains of laboratory animals, when fed AL every other day, are capable of gorging so that their net weekly intake is not greatly decreased. Despite having only a small deficit in energy intake relative to control levels, however, these animals experience enhanced longevity and stress resistance is enhanced in comparison to AL controls as much in animals enduring daily restriction of diet. These observations warrant renewed interest in this paradigm and suggest that comparisons of the paradigms and their effects can be used to determine which factors are critical to the beneficial effects of caloric restriction.

Key words

aging caloric restriction dietary restriction fasting longevity 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Anson RM, Guo Z, de Cabo R, Iyun T, Rios M and Hagepanos A et al. (2003) Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake. Proc Natl Acad Sci USA 100(10): 6216–6220CrossRefPubMedGoogle Scholar
  2. Arias-Vallejo E (1957) La dieta de hambre a dias alternos en la alimentacion de los viejos. Prensa Med Argent 2(44): 119–120Google Scholar
  3. Barrows CH Jr, Kokkonen G (1978) The effect of various dietary restricted regimes on biochemical variables in the mouse. Growth 42(1): 71–85PubMedGoogle Scholar
  4. Bartke A, Wright JC, Mattison JA, Ingram DK, Miller RA, Roth GS (2001) Extending the lifespan of long-lived mice. Nature 414(6862): 412CrossRefPubMedGoogle Scholar
  5. Beauchene RE, Bales CW, Bragg CS, Hawkins ST, Mason RL (1986) Effect of age of initiation of feed restriction on growth, body composition, and longevity of rats. J Gerontol 41(1): 13–19PubMedGoogle Scholar
  6. Berg BN and Simms HS (1961) Nutrition and longevity in the rat. III. Food restriction beyond 800 days. J Nutr 74: 23–32Google Scholar
  7. Carlson AJ and Hoelzel F (1946) Apparent prolongation of the life span of rats by intermittent fasting. J Nutr 31: 363–375Google Scholar
  8. Everitt AV, Seedsman NJ and Jones F (1980) The effects of hypophysectomy and continuous food restriction, begun at ages 70 and 400 days, on collagen aging, proteinuria, incidence of pathology and longevity in the male rat. Mech Ageing Dev 12(2): 161–172CrossRefPubMedGoogle Scholar
  9. Goodrick CL, Ingram DK, Reynolds MA, Freeman JR and Cider NL (1982) Effects of intermittent feeding upon growth and life span in rats. Gerontology 28(4): 233–241PubMedGoogle Scholar
  10. Goodrick CL, Ingram DK, Reynolds MA, Freeman JR and Cider NL (1983a) Differential effects of intermittent feeding and voluntary exercise on body weight and lifespan in adult rats. J Gerontol 38(1): 36–45PubMedGoogle Scholar
  11. Goodrick CL, Ingram DK, Reynolds MA, Freeman JR and Cider NL (1983) Effects of intermittent feeding upon growth, activity, and lifespan in rats allowed voluntary exercise. Exp Aging Res 9(3): 203–209PubMedGoogle Scholar
  12. Goodrick CL, Ingram DK, Reynolds MA, Freeman JR and Cider N (1990) Effects of intermittent feeding upon body weight and lifespan in inbred mice: interaction of genotype and age. Mech Ageing Dev 55(1): 69–87PubMedGoogle Scholar
  13. Holloszy JO and Smith EK (1986) Longevity of cold-exposed rats: A reevaluation of the “rate-of-living theory.” J Appl Physiol 61(5): 1656–60.PubMedGoogle Scholar
  14. Ingram DK and Reynolds MA (1987) The relationship of body weight to longevity within laboratory rodent species. In Woodhead AD, Thompson KH (eds) Evolution of Longevity in Animals, pp 247–282 Plenum Press, New YorkGoogle Scholar
  15. Klurfeld DM, Weber MM and Kritchevsky D (1987) Inhibition of chemically induced mammary and colon tumor promotion by caloric restriction in rats fed increased dietary fat. Cancer Res 47(11): 2759–2762PubMedGoogle Scholar
  16. Mair W, Goymer P, Pletcher SD and Partridge L (2003) Demography of dietary restriction and death in Drosophila. Science 301(5640): 1731–1733PubMedGoogle Scholar
  17. Masoro EJ (2003) Subfield history: caloric restriction, slowing aging, and extending life. Sci Aging Knowledge Environ 2003(8): RE2PubMedGoogle Scholar
  18. Masoro EJ, Yu BP and Bertrand HA (1982) Action of food restriction in delaying the aging process. Proc Natl Acad Sci U S A 79(13): 4239–4241PubMedGoogle Scholar
  19. McCay CM, Maynard LA, Sperling G and Barnes LL (1937) Retarded growth, lifespan, ultimate body size, and age changes in the albino rat after feeding diets restricted in calories. J Nutr 18: 1–13Google Scholar
  20. Merry BJ and Holehan AM (1981) Serum profiles of lh, fsh, testosterone and 5 alpha-dht from 21 to 1000 days of age in ad libitum fed and dietary restricted rats. Exp Gerontol 16(6): 431–444PubMedGoogle Scholar
  21. Osborne TB, Mendel LB and Ferry ER (1915) The resumption of growth after long continued failure to grow. J Biol Chem 23: 439–454Google Scholar
  22. Radak Z, Takahashi R, Kumiyama A, Nakamoto H, Ohno H, Ookawara T and Goto S (2002) Effect of aging and late onset dietary restriction on antioxidant enzymes and proteasome activities, and protein carbonylation of rat skeletal muscle and tendon. Exp Gerontol 37(12): 1423–1430PubMedGoogle Scholar
  23. Roth GS, Lane MA, Ingram DK, Mattison JA, Elahi D, Tobin JD, Muller D and Metter EJ (2002) Biomarkers of caloric restriction may predict longevity in humans. Science 297(5582): 811PubMedGoogle Scholar
  24. Rous F (1914) The influence of diet on transplant and spontaneous tumors. J Exp Med 20: 433–451Google Scholar
  25. Talan MI and Ingram DK (1985) Effect of intermittent feeding on thermoregulatory abilities of young and aged c57BL/6J mice. Arch Gerontol Geriatr 4(3): 251–259PubMedGoogle Scholar
  26. Van Remmen H, Ikeno Y, Hamilton M, Pahlavani M, Wolf N and Thorpe SR et al. (2003) Life-long reduction in mnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging. Physiol Genomics 16(1): 29–37PubMedGoogle Scholar
  27. Walford RL, Liu RK, Gerbase-Delima M, Mathies M and Smith GS (1973) Long-term dietary restriction and immune function in mice: response to sheep red blood cells and to mitogenic agents. Mech Ageing Dev 2(6): 447–454PubMedGoogle Scholar
  28. Wan R, Camandola S and Mattson MP (2003) Intermittent food deprivation improves cardiovascular and neuroendocrine responses to stress in rats. J Nutr 133(6): 1921–1929PubMedGoogle Scholar
  29. Weindruch R and Walford RL (1982) Dietary restriction in mice beginning at 1 year of age: effect on life-span and spontaneous cancer incidence. Science 215(4538): 1415–1418PubMedGoogle Scholar
  30. Weindruch R and Walford RL (1988) The Retardation of Aging and Disease by Dietary Restriction. C.C. Thomas, Springfield, IL, USAGoogle Scholar
  31. Yu BP (1996) Aging and oxidative stress: modulation by dietary restriction. Free Radic Biol Med 21(5): 651–668PubMedGoogle Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  • R. Michael Anson
    • 1
  • Bruce Jones
    • 1
  • Rafael de Cabod
    • 1
    • 2
    Email author
  1. 1.Laboratory of Experimental GerontologyThe National Institute on Aging, NIHBaltimoreUSA
  2. 2.Laboratory of Experimental GerontologyGerontology Research CenterBaltimoreUSA

Personalised recommendations