Skip to main content

Advertisement

Log in

The Underexplored Dimensions of Nutritional Hormesis

  • Functional Foods (I Rudkowska, Section Editor)
  • Published:
Current Nutrition Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Hormesis is biphasic response wherein low and high doses of chemical and nutrient confer beneficial and toxic effects respectively, typically in a U-shaped manner. Hormesis is intricately related to bioenergetic state of a cell, and therefore, nutrition impacts it. Excessive nutrition can halt the endogenous antioxidant synthesis leading to cytotoxic effects. While low and optimum doses of the same bring about hormetic stimulation that can exalt the antioxidant response and reduce susceptibility towards degenerative diseases. The sirtuin family of proteins is triggered by mild stress of calorie restriction and exerts hormesis. Similarly, several phytochemicals and micronutrients are known to bring about health benefits at optimum dose and deleterious effects at high doses. Despite this attribute, nutritional hormesis is not very well researched upon because the magnitude of hormetic effect observed is generally quite modest. There is no precise regulation of optimal intake of certain foods to witness hormesis and no characterization of any biomarker that reports stress responses at various doses above or below optimal intakes. There is a major gap in research between nutrition and hormesis being affected by sirtuin family of proteins, phytochemicals, and micronutrients.

Recent Findings

Mild stress of calorie restriction elevates sirtuin protein and effect of sirtuin protein on hormesis has been recently reported.

Summary

More foods that enhance sirtuin protein, phytochemicals, and micronutrients need to be explored in relation to hormesis and associated health benefits.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of outstanding importance

  1. Bhakta-Guha D, Efferth T. Hormesis: decoding two sides of the same coin. Pharmaceuticals. 2015;8(4):865–83. https://doi.org/10.3390/ph8040865.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ingram DK, Roth GS. Calorie restriction mimetics: can you have your cake and eat it, too? Ageing Res Rev. 2015;1(20):46–62. https://doi.org/10.1016/j.arr.2014.11.005.

    Article  Google Scholar 

  3. •• Antonucci S, Mulvey JF, Burger N, Di Sante M, Hall AR, Hinchy EC, Caldwell ST, Gruszczyk AV, Deshwal S, Hartley RC, Kaludercic N. Selective mitochondrial superoxide generation in vivo is cardioprotective through hormesis. Free Radical Biol Med. 2019;1(134):678–87. https://doi.org/10.1016/j.freeradbiomed.2019.01.034. This study elaborates how the concept of hormesis helps to rationalize the paradoxical effect of both injury and protection elicited by reactive oxygen spcies.

    Article  CAS  Google Scholar 

  4. Mattson MP, Calabrese EJ. A revolution in biology, toxicology and medicine. New York: Springer; 2010. https://doi.org/10.1007/978-1-60761-495-1.

  5. Radak Z, Chung HY, Koltai E, Taylor AW, Goto S. Exercise, oxidative stress and hormesis. Ageing Res Rev. 2008;1;7(1):34–42. https://doi.org/10.1016/j.arr.2007.04.004.

    Article  CAS  Google Scholar 

  6. Crovesy L, Rosado EL. Interaction between genes involved in energy intake regulation and diet in obesity. Nutrition. 2019;1(67): 110547. https://doi.org/10.1016/j.nut.2019.06.027.

    Article  CAS  Google Scholar 

  7. Nogueiras R, Habegger KM, Chaudhary N, Finan B, Banks AS, Dietrich MO, Horvath TL, Sinclair DA, Pfluger PT, Tschöp MH. Sirtuin 1 and sirtuin 3: physiological modulators of metabolism. Physiol Rev. 2012. https://doi.org/10.1152/physrev.00022.2011.

    Article  PubMed  Google Scholar 

  8. Liberek K, Lewandowska A, Ziętkiewicz S. Chaperones in control of protein disaggregation. EMBO J. 2008;23;27(2):328–35. https://doi.org/10.1038/sj.emboj.7601970.

    Article  CAS  Google Scholar 

  9. Pande S, Kratasyuk VA, Medvedeva NN, Kolenchukova OA, Salmina AB. Nutritional biomarkers: current view and future perspectives. Crit Rev Food Sci Nutr. 2018;58(18):3055–69.https://doi.org/10.1080/10408398.2017.1350136.

  10. Yen WL, Klionsky DJ. How to live long and prosper: autophagy, mitochondria, and aging. Physiology. 2008;23(5):248–62. https://doi.org/10.1152/physiol.00013.2008.

    Article  CAS  PubMed  Google Scholar 

  11. Salminen A, Kaarniranta K. ER stress and hormetic regulation of the aging process. Ageing Res Rev. 2010;1;9(3):211–7. https://doi.org/10.1016/j.arr.2010.04.003.

    Article  CAS  Google Scholar 

  12. Pomatto LC, Dill T, Carboneau B, Levan S, Kato J, Mercken EM, Pearson KJ, Bernier M, de Cabo R. Deletion of Nrf2 shortens lifespan in C57BL6/J male mice but does not alter the health and survival benefits of caloric restriction. Free Radical Biol Med. 2020;20(152):650–8. https://doi.org/10.1016/j.freeradbiomed.2020.01.005.

    Article  CAS  Google Scholar 

  13. Martucci M, Ostan R, Biondi F, Bellavista E, Fabbri C, Bertarelli C, Salvioli S, Capri M, Franceschi C, Santoro A. Mediterranean diet and inflammaging within the hormesis paradigm. Nutr Rev. 2017;1;75(6):442–55. https://doi.org/10.1093/nutrit/nux013.

    Article  Google Scholar 

  14. Dattilo S, Mancuso C, Koverech G, Di Mauro P, Ontario ML, Petralia CC, Petralia A, Maiolino L, Serra A, Calabrese EJ, Calabrese V. Heat shock proteins and hormesis in the diagnosis and treatment of neurodegenerative diseases. Immun Ageing. 2015;12(1):1–9. https://doi.org/10.1186/s12979-015-0046-8.

    Article  CAS  Google Scholar 

  15. Mattson MP. Awareness of hormesis will enhance future research in basic and applied neuroscience. Crit Rev Toxicol. 2008;1;38(7):633–9. https://doi.org/10.1080/10408440802026406.

    Article  CAS  Google Scholar 

  16. Hayes DP. Nutritional hormesis. Eur J Clin Nutr. 2007;61(2):147–59. https://doi.org/10.1038/sj.ejcn.1602507.

    Article  CAS  PubMed  Google Scholar 

  17. Forman HJ, Davies KJ, Ursini F. How do nutritional antioxidants really work: nucleophilic tone and para-hormesis versus free radical scavenging in vivo. Free Radical Biol Med. 2014;8(66):24–35. https://doi.org/10.1016/j.freeradbiomed.2013.05.045.

    Article  CAS  Google Scholar 

  18. Hyun DH, Emerson SS, Jo DG, Mattson MP, De Cabo R. Calorie restriction up-regulates the plasma membrane redox system in brain cells and suppresses oxidative stress during aging. Proc Natl Acad Sci. 2006;26;103(52):19908–12. https://doi.org/10.1073/pnas.0608008103.

    Article  CAS  Google Scholar 

  19. • Pande S, Ranjan R, Shuvaev AN, Malinovskaya NA, Ryazanova M, Salmina AB, Kolenchukova OA, Kratasyuk VA. Dietary buckwheat enhances sirtuin1 without calorie restriction. J Cereal Sci. 2020;1(94): 103004. https://doi.org/10.1016/j.jcs.2020.103004. This study discusses the CR mimicking effect of indigestible dietary fiber present in buckwheat in improving sirtuin1 protein expression. Buckwheat improved sirtuin1 protein expression without compromising the body weight and tissue protein unlike rats subjected to CR.

    Article  CAS  Google Scholar 

  20. Grabowska W, Sikora E, Bielak-Zmijewska A. Sirtuins, a promising target in slowing down the ageing process. Biogerontology. 2017;1;18(4):447–76. https://doi.org/10.1007/s10522-017-9685-9.

    Article  CAS  Google Scholar 

  21. Michan S, Sinclair D. Sirtuins in mammals: insights into their biological function. Biochem J. 2007;15;404(1):1–3. https://doi.org/10.1042/BJ20070140.

    Article  CAS  Google Scholar 

  22. Bagul PK, Katare PB, Bugga P, Dinda AK, Banerjee SK. SIRT-3 modulation by resveratrol improves mitochondrial oxidative phosphorylation in diabetic heart through deacetylation of TFAM. Cells. 2018;7(12):235. https://doi.org/10.3390/cells7120235.

    Article  CAS  PubMed Central  Google Scholar 

  23. Masoro EJ. Overview of caloric restriction and ageing. Mech Ageing Dev. 2005;1;126(9):913–22. https://doi.org/10.1016/j.mad.2005.03.012.

    Article  CAS  Google Scholar 

  24. Someya S, Yu W, Hallows WC, Xu J, Vann JM, Leeuwenburgh C, Tanokura M, Denu JM, Prolla TA. Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell. 2010;24;143(5):802–12. https://doi.org/10.1016/j.cell.2010.10.002.

    Article  CAS  Google Scholar 

  25. Chen CC, Kuo CH, Leu YL, Wang SH. Corylin reduces obesity and insulin resistance and promotes adipose tissue browning through SIRT-1 and β3-AR activation. Pharmacol Res. 2021;1(164): 105291. https://doi.org/10.1016/j.phrs.2020.105291.

    Article  CAS  Google Scholar 

  26. Arima Y, Nakagawa Y, Takeo T, Ishida T, Yamada T, Hino S, Nakao M, Hanada S, Umemoto T, Suda T, Sakuma T. Murine neonatal ketogenesis preserves mitochondrial energetics by preventing protein hyperacetylation. Nat Metab. 2021;3(2):196–210. https://doi.org/10.1038/s42255-021-00342-6.

    Article  CAS  PubMed  Google Scholar 

  27. Biganeh J, Ashtarinezhad A, Behzadipour D, Khanjani N, Tavakoli Nik A, Bagheri HM. Investigating the relationship between job stress, workload and oxidative stress in nurses. Int J Occup Saf Ergon. 2021;11:1–7. https://doi.org/10.1080/10803548.2021.1877456.

    Article  Google Scholar 

  28. Merksamer PI, Liu Y, He W, Hirschey MD, Chen D, Verdin E. The sirtuins, oxidative stress and aging: an emerging link. Aging (Albany NY). 2013;5(3):144. https://doi.org/10.18632/aging.100544.

  29. Corbi G, Conti V, Komici K, Manzo V, Filippelli A, Palazzo M, Vizzari F, Davinelli S, Di Costanzo A, Scapagnini G, Ferrara N. Phenolic plant extracts induce Sirt1 activity and increase antioxidant levels in the rabbit’s heart and liver. Oxid Med Cell Longev. 2018;4:2018. https://doi.org/10.1155/2018/2731289.

    Article  CAS  Google Scholar 

  30. Pallauf K, Giller K, Huebbe P, Rimbach G. Nutrition and healthy ageing: calorie restriction or polyphenol-rich “MediterrAsian” diet?. Oxid Med Cell Longev. 2013;2013. https://doi.org/10.1155/2013/707421.

  31. Blokker BA, Maijo M, Echeandia M, Galduroz M, Patterson AM, Ten A, Philo M, Schungel R, Gutierrez-de Juan V, Halilbasic E, Fuchs C. Fine-tuning of sirtuin 1 expression is essential to protect the liver from cholestatic liver disease. Hepatology. 2019;69(2):699–716. https://doi.org/10.1002/hep.30275.

    Article  CAS  PubMed  Google Scholar 

  32. de Oliveira SE, Batista R. Ferulic acid and naturally occurring compounds bearing a feruloyl moiety: a review on their structures, occurrence, and potential health benefits. Compr Rev Food Sci Food Safety. 2017;16(4):580–616. https://doi.org/10.1016/j.freeradbiomed.2013.05.045.

    Article  CAS  Google Scholar 

  33. Chowdhury S, Ghosh S, Das AK, Sil PC. Ferulic acid protects hyperglycemia-induced kidney damage by regulating oxidative insult, inflammation and autophagy. Front Pharmacol. 2019;5(10):27. https://doi.org/10.3389/fphar.2019.00027.

    Article  CAS  Google Scholar 

  34. Gunasekaran S, Venkatachalam K, Namasivayam N. Anti-inflammatory and anticancer effects of p-methoxycinnamic acid, an active phenylpropanoid, against 1, 2-dimethylhydrazine-induced rat colon carcinogenesis. Mol Cell Biochem. 2019;30;451(1–2):117–29. https://doi.org/10.1007/s11010-018-3398-5.

    Article  CAS  Google Scholar 

  35. Calabrese EJ, Agathokleous E, Calabrese V. Ferulic acid and hormesis: biomedical and environmental implications. Mech Ageing Dev. 2021;1(198): 111544. https://doi.org/10.1016/j.mad.2021.111544.

    Article  CAS  Google Scholar 

  36. Dayalan Naidu S, Suzuki T, Yamamoto M, Fahey JW, Dinkova-Kostova AT. Phenethyl isothiocyanate, a dual activator of transcription factors NRF2 and HSF1. Mol Nutr Food Res. 2018;62(18):1700908. https://doi.org/10.1002/mnfr.201700908.

    Article  CAS  PubMed Central  Google Scholar 

  37. Upadhyaya B, Liu Y, Dey M. Phenethyl isothiocyanate exposure promotes oxidative stress and suppresses Sp1 transcription factor in cancer stem cells. Int J Mol Sci. 2019;20(5):1027. https://doi.org/10.3390/ijms20051027.

    Article  CAS  PubMed Central  Google Scholar 

  38. Hong YH, Uddin M, Jo U, Kim B, Suh DH, Kim HS, Song J, Song YS. ROS accumulation by PEITC selectively kills ovarian cancer cells via UPR-mediated apoptosis. Front Oncol. 2015;28(5):167. https://doi.org/10.3389/fonc.2015.00167.

    Article  Google Scholar 

  39. Teertam SK, Jha S. Up-regulation of Sirt1/miR-149-5p signaling may play a role in resveratrol induced protection against ischemia via p53 in rat brain. J Clin Neurosci. 2020;1(72):402–11. https://doi.org/10.1016/j.jocn.2019.11.043.

    Article  CAS  Google Scholar 

  40. Karbowska M, Kaminski TW, Znorko B, Domaniewski T, Misztal T, Rusak T, Pryczynicz A, Guzinska-Ustymowicz K, Pawlak K, Pawlak D. Indoxyl sulfate promotes arterial thrombosis in rat model via increased levels of complex TF/VII, PAI-1, platelet activation as well as decreased contents of SIRT1 and SIRT3. Front Physiol. 2018;28(9):1623. https://doi.org/10.3389/fphys.2018.01623.

    Article  Google Scholar 

  41. Molinari R, Costantini L, Timperio AM, Lelli V, Bonafaccia F, Bonafaccia G, Merendino N. Tartary buckwheat malt as ingredient of gluten-free cookies. J Cereal Sci. 2018;1(80):37–43. https://doi.org/10.1016/j.jcs.2017.11.011.

    Article  CAS  Google Scholar 

  42. Watjen W, Michels G, Steffan B, Niering P, Chovolou Y, Kampkotter A, Tran-Thi QH, Proksch P, Kahl R. Low concentrations of flavonoids are protective in rat H4IIE cells whereas high concentrations cause DNA damage and apoptosis. J Nutr. 2005;1;135(3):525–31. https://doi.org/10.1093/jn/135.3.525.

    Article  Google Scholar 

  43. Vargas AJ, Burd R. Hormesis and synergy: pathways and mechanisms of quercetin in cancer prevention and management. Nutr Rev. 2010;1;68(7):418–28. https://doi.org/10.1111/j.1753-4887.2010.00301.x.

    Article  Google Scholar 

  44. •• Mehdi MM, Solanki P, Singh P. Oxidative stress, antioxidants, hormesis and calorie restriction: the current perspective in the biology of aging. Arch Gerontol Geriatr. 2021;2:104413. https://doi.org/10.1016/j.archger.2021.104413. This study outlines the antiaging potential of hormesis in terms of restoring molecular damage and promoting anabolism.

  45. Albanes D. β-Carotene and lung cancer: a case study. Am J Clin Nutr. 1999;69(6):1345S-S1350. https://doi.org/10.1093/ajcn/69.6.1345s1.

    Article  CAS  PubMed  Google Scholar 

  46. Sano M, Fukuda K. Editorial: Activation of mitochondrial biogenesis by hormesis. Circ Res. 2008;103:1191–3.

    Article  CAS  Google Scholar 

  47. Pockley AG. Heat shock proteins in health and disease: therapeutic targets or therapeutic agents? Expert Rev Mol Med. 2001;3:1–21.

    Article  CAS  Google Scholar 

  48. Martel J, Ojcius DM, Ko Y, Young JD. Phytochemicals as prebiotics and biological stress inducers. Trends Biochem Sci Elsevier Ltd. 2020;45:462–71.

    Article  CAS  Google Scholar 

  49. Maynard KI. Hormesis pervasiveness and its potential implications for pharmaceutical research and development. Dose-Response. 2011;9:377–86.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The first author (SP) acknowledges SERB Ramanujan fellowship (RJF/2020/000026) provided by the Department of Science and Technology, Government of India.

Author information

Authors and Affiliations

Authors

Contributions

Conceptualization and writing original draft—Shubhra Pande; writing—review and editing—Sheikh Raisuddin.

Corresponding author

Correspondence to Shubhra Pande.

Ethics declarations

Conflict of Interest

There is no conflict of interest (financial or non-financial).

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Functional Foods

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pande, S., Raisuddin, S. The Underexplored Dimensions of Nutritional Hormesis. Curr Nutr Rep 11, 386–394 (2022). https://doi.org/10.1007/s13668-022-00423-2

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13668-022-00423-2

Keywords

Navigation