Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Health issues and nutrition in the elderly

Causal associations of plasma omega-3 polyunsaturated fatty acids with sarcopenia-related traits: a two-sample Mendelian randomization study

European Journal of Clinical Nutrition volume 78, pages 19–26 (2024)Cite this article

Subjects

Abstract

Objective

To evaluate the causal effect of plasma omega-3 polyunsaturated fatty acids (PUFAs) on sarcopenia-related traits (lean mass, grip strength and walking pace) utilizing two-sample Mendelian randomization (MR) approach.

Methods

Based on genome-wide association study (GWAS) summary statistics, we performed two-sample MR applying the inverse variance weighted (IVW) as the primary method, supplemented with four additional sensitivity analyses. Furthermore, multivariable MR (MVMR) was applied to assess these associations independent of alcohol drinking, type 2 diabetes (T2D), triglycerides (TG), estimated glomerular filtration rate (eGFR) and C-reactive protein (CRP).

Results

In univariable MR, the IVW analysis suggested no significant causal effect of genetically determined plasma omega-3 PUFAs on fat-free mass (right leg: β = 0.01, 95% CI = −0.02 to 0.05, P = 0.375; left leg: β = 0.01, 95% CI = −0.02 to 0.04, P = 0.446; right arm: β = 0.01, 95% CI = −0.02 to 0.05, P = 0.376; left arm: β = 0.01, 95% CI = −0.02 to 0.04, P = 0.384; trunk:β = 0.02, 95% CI = −0.02 to 0.06, P = 0.283; whole: β = 0.01, 95% CI = −0.03 to 0.04, P = 0.631), grip strength (right hand: β = −0.01, 95% CI = −0.03 to 0.01, P = 0.387; left hand: β = −0.01, 95% CI = −0.02 to 0.01, P = 0.553) and walking pace (β = 0.00, 95% CI = −0.01 to 0.02, P = 0.575), and sensitive analysis generated similar non-significant results. Furthermore, the MVMR revealed no independent causal association.

Conclusions

Genetically determined plasma omega-3 PUFAs have no causal effect on sarcopenia-related traits.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: The schematic diagram of our present two-sample Mendelian randomization (MR) study design.
Fig. 2: Estimated casual associations of plasma omega-3 PUFAs with FFM using different MR methods.
Fig. 3: Estimated casual associations of plasma omega-3 PUFAs with grip strength using different MR methods.
Fig. 4: Estimated causal associations of plasma omega-3 PUFAs with walking pace using different MR methods.

Similar content being viewed by others

Data availability

Data are available from the corresponding author upon reasonable request.

References

  1. Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing 2019;48:16–31.

    Article  Google Scholar 

  2. Mayhew AJ, Amog K, Phillips S, Parise G, McNicholas PD, de Souza RJ, et al. The prevalence of sarcopenia in community-dwelling older adults, an exploration of differences between studies and within definitions: a systematic review and meta-analyses. Age Ageing. 2019;48:48–56.

    Article  CAS  PubMed  Google Scholar 

  3. Beaudart C, Rizzoli R, Bruyère O, Reginster JY, Biver E. Sarcopenia: burden and challenges for public health. Arch Public Health. 2014;72:45.

    Article  PubMed Central  Google Scholar 

  4. Morley JE, Argiles JM, Evans WJ, Bhasin S, Cella D, Deutz NE, et al. Nutritional recommendations for the management of sarcopenia. J Am Med Dir Assoc. 2010;11:391–6.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Ferguson EJ, Seigel JW, McGlory C. Omega-3 fatty acids and human skeletal muscle. Curr Opin Clin Nutr Metab Care. 2021;24:114–9.

    Article  CAS  PubMed  Google Scholar 

  6. Calder PC. Omega-3 fatty acids and inflammatory processes: from molecules to man. Biochem Soc Trans. 2017;45:1105–15.

    Article  CAS  Google Scholar 

  7. Jeromson S, Mackenzie I, Doherty MK, Whitfield PD, Bell G, Dick J, et al. Lipid remodeling and an altered membrane-associated proteome may drive the differential effects of EPA and DHA treatment on skeletal muscle glucose uptake and protein accretion. Am J Physiol Endocrinol Metab. 2018;314:E605–19.

    Article  CAS  Google Scholar 

  8. Dupont J, Dedeyne L, Dalle S, Koppo K, Gielen E. The role of omega-3 in the prevention and treatment of sarcopenia. Aging Clin Exp Res. 2019;31:825–36.

    Article  PubMed Central  Google Scholar 

  9. Zhang Y, Guo H, Liang J, Xiao W, Li Y. Relationship Between Dietary Omega-3 and Omega-6 Polyunsaturated Fatty Acids Level and Sarcopenia. A Meta-Analysis of Observational Studies. Front Nutr. 2021;8:738083.

    Article  Google Scholar 

  10. Wong TC, Chen YT, Wu PY, Chen TW, Chen HH, Chen TH, et al. Ratio of Dietary n-6/n-3 Polyunsaturated fatty acids independently related to muscle mass decline in hemodialysis patients. PLoS One. 2015;10:e0140402.

    Article  PubMed  PubMed Central  Google Scholar 

  11. de Branco FMS, Rossato LT, Rinaldi AEM, Azeredo CM, de Oliveira EP. Plasma omega-3 is not associated with appendicular muscle mass index in young and middle-aged individuals: Results from NHANES 2011-2012. Prostaglandins Leukot Ess Fat Acids. 2022;178:102412.

    Article  Google Scholar 

  12. Bae YJ, Cui XS, Shin SH. Increased Omega-3 Fatty Acid Intake Is Associated with Low Grip Strength in Elderly Korean Females. Nutrients. 2022;14:2374.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Frison E, Boirie Y, Peuchant E, Tabue-Teguo M, Barberger-Gateau P, Féart C. Plasma fatty acid biomarkers are associated with gait speed in community-dwelling older adults: The Three-City-Bordeaux study. Clin Nutr. 2017;36:416–22.

    Article  CAS  PubMed  Google Scholar 

  14. Reinders I, Song X, Visser M, Eiriksdottir G, Gudnason V, Sigurdsson S, et al. Plasma phospholipid PUFAs are associated with greater muscle and knee extension strength but not with changes in muscle parameters in older adults. J Nutr. 2015;145:105–12.

    Article  CAS  PubMed  Google Scholar 

  15. Reinders I, Murphy RA, Song X, Visser M, Cotch MF, Lang TF, et al. Polyunsaturated fatty acids in relation to incident mobility disability and decline in gait speed; the Age, Gene/Environment Susceptibility-Reykjavik Study. Eur J Clin Nutr. 2015;69:489–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Lengelé L, Moehlinger P, Bruyère O, Locquet M, Reginster JY, Beaudart C. Association between Changes in Nutrient Intake and Changes in Muscle Strength and Physical Performance in the SarcoPhAge Cohort. Nutrients. 2020;12:3485.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Nilsson MI, Mikhail A, Lan L, Di Carlo A, Hamilton B, Barnard K, et al. A Five-Ingredient Nutritional Supplement and Home-Based Resistance Exercise Improve Lean Mass and Strength in Free-Living Elderly. Nutrients. 2020;12:2391.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Strandberg E, Edholm P, Ponsot E, Wåhlin-Larsson B, Hellmén E, Nilsson A, et al. Influence of combined resistance training and healthy diet on muscle mass in healthy elderly women: a randomized controlled trial. J Appl Physiol. 1985;2015:918–925.

    Google Scholar 

  19. Strike SC, Carlisle A, Gibson EL, Dyall SC. A High Omega-3 Fatty Acid Multinutrient Supplement Benefits Cognition and Mobility in Older Women: A Randomized, Double-blind, Placebo-controlled Pilot Study. J Gerontol A Biol Sci Med Sci. 2016;71:236–42.

    Article  CAS  PubMed  Google Scholar 

  20. Rolland Y, Barreto PS, Maltais M, Guyonnet S, Cantet C, Andrieu S, et al. Effect of Long-Term Omega 3 Polyunsaturated Fatty Acid Supplementation with or without Multidomain Lifestyle Intervention on Muscle Strength in Older Adults: Secondary Analysis of the Multidomain Alzheimer Preventive Trial (MAPT). Nutrients. 2019;11:1931.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Healy LA, Ryan A, Doyle SL, Bhuachalla ÉBN, Cushen S, Segurado R, et al. Does Prolonged Enteral Feeding With Supplemental Omega-3 Fatty Acids Impact on Recovery Post-esophagectomy: Results of a Randomized Double-Blind Trial. Ann Surg. 2017;266:720–8.

    Article  Google Scholar 

  22. Lawlor DA, Harbord RM, Sterne JA, Timpson N, Davey Smith G. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med. 2008;27:1133–63.

    Article  PubMed  Google Scholar 

  23. Smith GD, Ebrahim S. ‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol. 2003;32:1–22.

    Article  PubMed  Google Scholar 

  24. Staley JR, Blackshaw J, Kamat MA, Ellis S, Surendran P, Sun BB, et al. PhenoScanner: a database of human genotype-phenotype associations. Bioinformatics. 2016;32:3207–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Kettunen J, Demirkan A, Würtz P, Draisma HH, Haller T, Rawal R, et al. Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA. Nat Commun. 2016;7:11122.

    Article  CAS  PubMed Central  Google Scholar 

  26. Sudlow C, Gallacher J, Allen N, Beral V, Burton P, Danesh J, et al. UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 2015;12:e1001779.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Visser M, Fuerst T, Lang T, Salamone L, Harris TB. Validity of fan-beam dual-energy X-ray absorptiometry for measuring fat-free mass and leg muscle mass. Health, Aging, and Body Composition Study-Dual-Energy X-ray Absorptiometry and Body Composition Working Group. J Appl Physiol. 1985;1999:1513–1520.

    Google Scholar 

  28. Roberts HC, Denison HJ, Martin HJ, Patel HP, Syddall H, Cooper C, et al. A review of the measurement of grip strength in clinical and epidemiological studies: towards a standardised approach. Age Ageing. 2011;40:423–9.

    Article  PubMed  Google Scholar 

  29. Wind AE, Takken T, Helders PJ, Engelbert RH. Is grip strength a predictor for total muscle strength in healthy children, adolescents, and young adults? Eur J Pediatr. 2010;169:281–7.

    Article  PubMed  Google Scholar 

  30. Xue A, Wu Y, Zhu Z, Zhang F, Kemper KE, Zheng Z, et al. Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes. Nat Commun. 2018;9:2941.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Willer CJ, Schmidt EM, Sengupta S, Peloso GM, Gustafsson S, Kanoni S, et al. Discovery and refinement of loci associated with lipid levels. Nat Genet. 2013;45:1274–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Pattaro C, Teumer A, Gorski M, Chu AY, Li M, Mijatovic V, et al. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function. Nat Commun. 2016;7:10023.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ligthart S, Vaez A, Võsa U, Stathopoulou MG, de Vries PS, Prins BP, et al. Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders. Am J Hum Genet. 2018;103:691–706.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Glymour MM, Tchetgen Tchetgen EJ, Robins JM. Credible Mendelian randomization studies: approaches for evaluating the instrumental variable assumptions. Am J Epidemiol. 2012;175:332–9.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Burgess S, Thompson SG. Avoiding bias from weak instruments in Mendelian randomization studies. Int J Epidemiol. 2011;40:755–64.

    Article  PubMed  Google Scholar 

  36. Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol. 2015;44:512–25.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Burgess S, Thompson SG. Interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol. 2017;32:377–89.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Bowden J, Davey Smith G, Haycock PC, Burgess S. Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator. Genet Epidemiol. 2016;40:304–14.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Hartwig FP, Davey Smith G, Bowden J. Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption. Int J Epidemiol. 2017;46:1985–98.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Verbanck M, Chen CY, Neale B, Do R. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet. 2018;50:693–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Burgess S, Thompson SG. Multivariable Mendelian randomization: the use of pleiotropic genetic variants to estimate causal effects. Am J Epidemiol. 2015;181:251–60.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Dalle S, Rossmeislova L, Koppo K. The Role of Inflammation in Age-Related Sarcopenia. Front Physiol. 2017;8:1045.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Gerling CJ, Mukai K, Chabowski A, Heigenhauser GJF, Holloway GP, Spriet LL, et al. Incorporation of Omega-3 Fatty Acids Into Human Skeletal Muscle Sarcolemmal and Mitochondrial Membranes Following 12 Weeks of Fish Oil Supplementation. Front Physiol. 2019;10:348.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Santo André HC, Esteves GP, Barreto GHC, Longhini F, Dolan E, Benatti FB. The Influence of n-3PUFA Supplementation on Muscle Strength, Mass, and Function: A Systematic Review and Meta-Analysis. Adv Nutr. 2023;14:115–27.

    Article  Google Scholar 

  45. Cornish SM, Cordingley DM, Shaw KA, Forbes SC, Leonhardt T, Bristol A, et al. Effects of Omega-3 Supplementation Alone and Combined with Resistance Exercise on Skeletal Muscle in Older Adults: A Systematic Review and Meta-Analysis. Nutrients. 2022;14:2221.

    Article  CAS  PubMed Central  Google Scholar 

Download references

Acknowledgements

We sincerely thank all investigators for sharing the genome-wide association studies (GWASs) summary statistic data.

Funding

This work was supported by Zhejiang Provincial Natural Science Foundation of China (Grant No. LY20H260001).

Author information

Authors and Affiliations

  1. School of Public Health, Health Science Center, Ningbo University, Ningbo, Zhejiang, China

    Ting Jin, Mengqiao Wang, Zhen Zeng & Lina Zhang

  2. Institute of Geriatrics, The First Affiliated Hospital of Medical School, Ningbo University, Ningbo, Zhejiang, China

    Wenming He & Yifeng Mai

  3. Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China

    Han Cen

Authors
  1. Ting Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mengqiao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhen Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wenming He
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lina Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yifeng Mai
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Han Cen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be submitted for publication. LN (zhanglina@nbu.edu.cn), YF (fymaiyifeng@nbu.edu.cn) and HC (cenhan@nbu.edu.cn) had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Conception and design: TJ, LN, YF, and HC; Acquisition of data: TJ, QM, ZZ, WM, and HC; Analysis and interpretation of data: TJ, QM, ZZ, WM, LN, YF, and HC.

Corresponding authors

Correspondence to Lina Zhang, Yifeng Mai or Han Cen.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

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

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jin, T., Wang, M., Zeng, Z. et al. Causal associations of plasma omega-3 polyunsaturated fatty acids with sarcopenia-related traits: a two-sample Mendelian randomization study. Eur J Clin Nutr 78, 19–26 (2024). https://doi.org/10.1038/s41430-023-01339-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41430-023-01339-y

Search

Advanced search

Quick links