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:

Metabolism and Metabolomics

Effect of micronutrient supplementation in addition to nutritional therapy on clinical outcomes of medical inpatients: results of an updated systematic review and meta-analysis

European Journal of Clinical Nutrition volume 76, pages 964–972 (2022)Cite this article

Subjects

Abstract

Background

There is increasing evidence from randomized controlled trials showing that different types of nutritional support interventions improve clinical outcomes in malnourished medical inpatients. Whether trials using micronutrient supplementation in addition to nutritional therapy are superior to trials without micronutrient supplementation remains unclear.

Methods

This is a secondary analysis of a systematic search and meta-analysis. We searched Cochrane Library, MEDLINE, and EMBASE electronic database from inception to December 15, 2020, for randomized controlled trials comparing the nutritional support interventions vs. usual care on all-cause mortality (primary endpoint) of medical inpatients with nutritional risk. We stratified trials based on whether or not micronutrient supplementation was used as part of the nutritional strategy.

Results

We included 23 randomized controlled trials (5 trials with and 18 trials without micronutrient supplementation) with a total of 6745 patients. Overall, mortality was significantly lower in patients receiving nutritional support compared to control group patients with an odds ratio of 0.74 (95% CI 0.59–0.94, p = 0.01). There was no difference between trials with and without micronutrient supplementation on mortality (odds ratio 0.70 (95% CI 0.46–1.08) vs. 0.77 (95% CI 0.57–1.04), I2 = 0%, p for subgroup difference = 0.73). Similarly, no differences in effect were found regarding non-elective readmissions and length of hospital stay.

Conclusions

While nutritional support reduces mortality and improves other clinical outcomes, we did not find evidence that trials using micronutrient supplementation in addition to nutritional therapy were superior to trials with no supplementation. The role of micronutrient supplementation in addition to nutritional support needs further research.

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: Flow chart of studies’ selection.
Fig. 2: Forest plot comparing nutritional interventions vs. control for mortality, stratified by the use of micronutrients.
Fig. 3: Forest plot comparing nutritional intervention vs. control for the length of hospital stay, stratified by the use of micronutrients.

Similar content being viewed by others

References

  1. Berger MM, Pantet O, Schneider A, Ben-Hamouda N. Micronutrient deficiencies in medical and surgical inpatients. J Clin Med. 2019;8:931. https://doi.org/10.3390/jcm8070931

  2. Schuetz P, Gregoriano C, Keller U. Supplementation of the population during the COVID-19 pandemic with vitamins and micronutrients – how much evidence is needed? Swiss Med Wkly. 2021;151:w20522 https://doi.org/10.4414/smw.2021.20522.

    Article  PubMed  Google Scholar 

  3. Schuetz P, Seres D, Lobo DN, Gomes F, Kaegi-Braun N, Stanga Z. Management of disease-related malnutrition for patients being treated in hospital. Lancet. 2021;398:1927–38. https://doi.org/10.1016/S0140-6736(21)01451-3.

    Article  PubMed  Google Scholar 

  4. Bounoure L, Gomes F, Stanga Z, Keller U, Meier R, Ballmer P, et al. Detection and treatment of medical inpatients with or at-risk of malnutrition: suggested procedures based on validated guidelines. Nutrition. 2016;32:790–8. https://doi.org/10.1016/j.nut.2016.01.019.

    Article  PubMed  Google Scholar 

  5. Gomes F, Schuetz P, Bounoure L, Austin P, Ballesteros-Pomar M, Cederholm T, et al. ESPEN guidelines on nutritional support for polymorbid internal medicine patients. Clin Nutr. 2018;37:336–53. https://doi.org/10.1016/j.clnu.2017.06.025.

    Article  PubMed  Google Scholar 

  6. Schuetz P, Fehr R, Baechli V, Geiser M, Deiss M, Gomes F, et al. Individualised nutritional support in medical inpatients at nutritional risk: a randomised clinical trial. Lancet. 2019;393:2312–21. https://doi.org/10.1016/S0140-6736(18)32776-4.

    Article  PubMed  Google Scholar 

  7. Boullata JI, Carrera AL, Harvey L, Escuro AA, Hudson L, Mays A, et al. ASPEN safe practices for enteral nutrition therapy [formula: see text]. Jpen J Parenter Enter Nutr. 2017;41:15–103. https://doi.org/10.1177/0148607116673053.

    Article  Google Scholar 

  8. Deutz NE, Matheson EM, Matarese LE, Luo M, Baggs GE, Nelson JL, et al. Readmission and mortality in malnourished, older, hospitalized adults treated with a specialized oral nutritional supplement: a randomized clinical trial. Clin Nutr. 2016;35:18–26. https://doi.org/10.1016/j.clnu.2015.12.010.

    Article  PubMed  Google Scholar 

  9. World Health Organization and Food and Agriculture Organization of the United Nations 2006, WHO Press, WorldHealth Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland.

  10. Carr AC, Maggini S. Vitamin C and immune function. Nutrients. 2017;9:1211. https://doi.org/10.3390/nu9111211

  11. Hemila H. Vitamin C and infections. Nutrients. 2017;9:339. https://doi.org/10.3390/nu9040339

  12. Gunville CF, Mourani PM, Ginde AA. The role of vitamin D in prevention and treatment of infection. Inflamm Allergy Drug Targets. 2013;12:239–45. https://doi.org/10.2174/18715281113129990046.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Gomes F, Baumgartner A, Bounoure L, Bally M, Deutz NE, Greenwald JL, et al. Association of nutritional support with clinical outcomes among medical inpatients who are malnourished or at nutritional risk: an updated systematic review and meta-analysis. JAMA Netw Open. 2019;2:e1915138 https://doi.org/10.1001/jamanetworkopen.2019.15138.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Kaegi-Braun N, Faessli M, Kilchoer F, Dragusha S, Tribolet P, Gomes F, et al. Nutritional trials using high protein strategies and long duration of support show strongest clinical effects on mortality: results of an updated systematic review and meta-analysis. Clin Nutr ESPEN. 2021;45:45–54. https://doi.org/10.1016/j.clnesp.2021.08.003.

    Article  PubMed  Google Scholar 

  15. Bally MR, Blaser Yildirim PZ, Bounoure L, Gloy VL, Mueller B, Briel M, et al. Nutritional support and outcomes in malnourished medical inpatients: a systematic review and meta-analysis. JAMA Intern Med. 2016;176:43–53. https://doi.org/10.1001/jamainternmed.2015.6587.

    Article  PubMed  Google Scholar 

  16. Schuetz P, Blaser Yildirim PZ, Gloy VL, Briel M, Bally MR: Early nutritional therapy for malnourished or nutritionally at‐risk adult medical inpatients. Cochrane Database of Systematic Reviews 2014.

  17. Cano-Torres EA, Simental-Mendia LE, Morales-Garza LA, Ramos-Delgado JM, Reyes-Gonzalez MM, Sanchez-Nava VM, et al. Impact of nutritional intervention on length of hospital stay and mortality among hospitalized patients with malnutrition: a clinical randomized controlled trial. J Am Coll Nutr. 2017;36:235–9. https://doi.org/10.1080/07315724.2016.1259595.

    Article  PubMed  Google Scholar 

  18. Neelemaat F, Lips P, Bosmans JE, Thijs A, Seidell JC, van Bokhorst-de van der Schueren MA. Short-term oral nutritional intervention with protein and vitamin D decreases falls in malnourished older adults. J Am Geriatrics Soc. 2012;60:691–9. https://doi.org/10.1111/j.1532-5415.2011.03888.x.

    Article  Google Scholar 

  19. Yang PH, Lin MC, Liu YY, Lee CL, Chang NJ. Effect of nutritional intervention programs on nutritional status and readmission rate in malnourished older adults with pneumonia: a randomized control trial. Int J Environ Res Public Health. 2019;16:4758. https://doi.org/10.3390/ijerph16234758

  20. Volkert D, Hubsch S, Oster P, Schlierf G. Nutritional support and functional status in undernourished geriatric patients during hospitalization and 6-month follow-up. Aging (Milano). 1996;8:386–95. https://doi.org/10.1007/BF03339600.

    Article  CAS  Google Scholar 

  21. Vlaming S, Biehler A, Hennessey EM, Jamieson CP, Chattophadhyay S, Obeid OA, et al. Should the food intake of patients admitted to acute hospital services be routinely supplemented? A randomized placebo controlled trial. Clin Nutr. 2001;20:517–26. https://doi.org/10.1054/clnu.2001.0486

    Article  CAS  PubMed  Google Scholar 

  22. Starke J, Schneider H, Alteheld B, Stehle P, Meier R. Short-term individual nutritional care as part of routine clinical setting improves outcome and quality of life in malnourished medical patients. Clin Nutr. 2011;30:194–201. https://doi.org/10.1016/j.clnu.2010.07.021

    Article  PubMed  Google Scholar 

  23. Saudny-Unterberger H, Martin JG, Gray-Donald K. Impact of nutritional support on functional status during an acute exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1997;156:794–9. https://doi.org/10.1164/ajrccm.156.3.9612102.

    Article  CAS  PubMed  Google Scholar 

  24. Potter JM, Roberts MA, McColl JH, Reilly JJ. Protein energy supplements in unwell elderly patients–a randomized controlled trial. Jpen J Parenter Enter Nutr. 2001;25:323–9. https://doi.org/10.1177/0148607101025006323.

    Article  CAS  Google Scholar 

  25. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.2 (updated February 2021). Cochrane, 2021. Available from www.training.cochrane.org/handbook.

  26. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60. https://doi.org/10.1136/bmj.327.7414.557.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Sterne JA, Egger M. Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis. J Clin Epidemiol. 2001;54:1046–55. https://doi.org/10.1016/s0895-4356(01)00377-8.

    Article  CAS  PubMed  Google Scholar 

  28. Sharma Y, Thompson CH, Kaambwa B, Shahi R, Hakendorf P, Miller M. Investigation of the benefits of early malnutrition screening with telehealth follow up in elderly acute medical admissions. QJM. 2017;110:639–47. https://doi.org/10.1093/qjmed/hcx095.

    Article  CAS  PubMed  Google Scholar 

  29. Munk T, Beck AM, Holst M, Rosenbom E, Rasmussen HH, Nielsen MA, et al. Positive effect of protein-supplemented hospital food on protein intake in patients at nutritional risk: a randomised controlled trial. J Hum Nutr Dietetics. 2014;27:122–132. https://doi.org/10.1111/jhn.12210

    Article  CAS  Google Scholar 

  30. Hickson M, Bulpitt C, Nunes M, Peters R, Cooke J, Nicholl C, et al. Does additional feeding support provided by health care assistants improve nutritional status and outcome in acutely ill older in-patients?—a randomised control trial. Clin Nutr. 2004;23:69–77. https://doi.org/10.1016/s0261-5614(03)00090-6

    Article  PubMed  Google Scholar 

  31. Vermeeren MA, Wouters EF, Geraerts-Keeris AJ, Schols AM. Nutritional support in patients with chronic obstructive pulmonary disease during hospitalization for an acute exacerbation; a randomized controlled feasibility trial. Clin Nutr. 2004;23:1184–92. https://doi.org/10.1016/j.clnu.2004.03.008.

    Article  CAS  PubMed  Google Scholar 

  32. Somanchi M, Tao X, Mullin GE. The facilitated early enteral and dietary management effectiveness trial in hospitalized patients with malnutrition. J Parenter Enter Nutr. 2011;35:209–16. https://doi.org/10.1177/0148607110392234

    Article  Google Scholar 

  33. Bunout D, Aicardi V, Hirsch S, Petermann M, Kelly M, Silva G, et al. Nutritional support in hospitalized patients with alcoholic liver disease. Eur J Clin Nutr. 1989;43:615–21.

    CAS  PubMed  Google Scholar 

  34. Hogarth MB, Marshall P, Lovat LB, Palmer AJ, Frost CG, Fletcher AE, et al. Nutritional supplementation in elderly medical in-patients: a double-blind placebo-controlled trial. Age Ageing. 1996;25:453–7. https://doi.org/10.1093/ageing/25.6.453

    Article  CAS  PubMed  Google Scholar 

  35. Gazzotti C, Arnaud-Battandier F, Parello M, Farine S, Seidel L, Albert A, et al. Prevention of malnutrition in older people during and after hospitalisation: results from a randomised controlled clinical trial. Age Ageing. 2003;32:321–5. https://doi.org/10.1093/ageing/32.3.321.

    Article  PubMed  Google Scholar 

  36. Broqvist M, Arnqvist H, Dahlstrom U, Larsson J, Nylander E, Permert J. Nutritional assessment and muscle energy metabolism in severe chronic congestive heart failure–effects of long-term dietary supplementation. Eur Heart J. 1994;15:1641–50. https://doi.org/10.1093/oxfordjournals.eurheartj.a060447.

    Article  CAS  PubMed  Google Scholar 

  37. Holyday M, Daniells S, Bare M, Caplan GA, Petocz P, Bolin T. Malnutrition screening and early nutrition intervention in hospitalised patients in acute aged care: a randomised controlled trial. J Nutr Health Aging. 2012;16:562–8. https://doi.org/10.1007/s12603-012-0022-3

    Article  CAS  PubMed  Google Scholar 

  38. Gariballa S, Forster S, Walters S, Powers H. A randomized, double-blind, placebo-controlled trial of nutritional supplementation during acute illness. Am J Med. 2006;119:693–9. https://doi.org/10.1016/j.amjmed.2005.12.006.

    Article  CAS  PubMed  Google Scholar 

  39. Bonilla-Palomas JL, Gamez-Lopez AL, Castillo-Dominguez JC, Moreno-Conde M, Lopez Ibanez MC, Alhambra Exposito R, et al. Nutritional intervention in malnourished hospitalized patients with heart failure. Arch Med Res. 2016;47:535–40. https://doi.org/10.1016/j.arcmed.2016.11.005.

    Article  PubMed  Google Scholar 

  40. Feldblum I, German L, Castel H, Harman-Boehm I, Shahar DR. Individualized nutritional intervention during and after hospitalization: the nutrition intervention study clinical trial. J Am Geriatrics Soc. 2011;59:10–17. https://doi.org/10.1111/j.1532-5415.2010.03174.x.

    Article  Google Scholar 

Download references

Funding

This study was supported in part by the Swiss National Science Foundation (SNSF Professorship, PP00P3_150531/1) and the Research Council of the Kantonsspital Aarau (1410.000.044).

Author information

Author notes

  1. These authors contributed equally: Nina Kaegi-Braun, Sara Germann.

Authors and Affiliations

  1. University Department of Medicine, Clinic for Endocrinology, Diabetology, and Metabolism, Kantonsspital Aarau, Aarau, Switzerland

    Nina Kaegi-Braun, Sara Germann, Montserrat Faessli, Fiona Kilchoer, Pascal Tribolet, Filomena Gomes, Céline Bretscher, Beat Mueller & Philipp Schuetz

  2. Medical Faculty of the University of Basel, Basel, Switzerland

    Nina Kaegi-Braun, Sara Germann, Montserrat Faessli, Fiona Kilchoer, Pascal Tribolet, Filomena Gomes, Céline Bretscher, Beat Mueller & Philipp Schuetz

  3. Medical Faculty of the Università della Svizzera italiana, Lugano, Switzerland

    Saranda Dragusha

  4. Nutrition Science Program, The New York Academy of Sciences, New York, NY, USA

    Filomena Gomes

  5. NOVA Medical School, Universidade NOVA de Lisboa, Lisboa, Portugal

    Filomena Gomes

  6. Center for Translational Research in Aging and Longevity, Department of Health & Kinesiology, Texas A&M University, College Station, TX, USA

    Nicolaas E. Deutz

  7. Division of Diabetology, Endocrinology, Nutritional Medicine, & Metabolism, University Hospital Inselspital Bern, University of Bern, Bern, Switzerland

    Zeno Stanga

Authors
  1. Nina Kaegi-Braun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sara Germann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Montserrat Faessli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fiona Kilchoer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Saranda Dragusha
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Pascal Tribolet
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Filomena Gomes
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Céline Bretscher
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Nicolaas E. Deutz
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Zeno Stanga
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Beat Mueller
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Philipp Schuetz
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

NK-B, FG, and PS wrote the initial protocol. DG, MF, FK, FG, SD, SG, and NK-B performed the data extraction and performed the statistical analyses. DG, MF, FK, SD, SG, NK-B, and PS drafted the manuscript; all authors critically reviewed the manuscript and approved the final version. PS oversaw the study and acts as a guarantor.

Corresponding author

Correspondence to Philipp Schuetz.

Ethics declarations

Competing interests

The Institution of PS has previously received unrestricted grant money unrelated to this project from Nestlé Health Science and Abbott Nutrition. The institution of ZS received speaking honoraria and research support from Nestlé Health Science, Abbott Nutrition, and Fresenius Kabi. NED reported grants from Abbot Nutrition, Department of Defense and National Institutes of Health. All other authors report no conflicts of interest. All other authors confirm that they do not have a conflict of interest associated with this manuscript.

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

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kaegi-Braun, N., Germann, S., Faessli, M. et al. Effect of micronutrient supplementation in addition to nutritional therapy on clinical outcomes of medical inpatients: results of an updated systematic review and meta-analysis. Eur J Clin Nutr 76, 964–972 (2022). https://doi.org/10.1038/s41430-021-01061-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41430-021-01061-7

This article is cited by

Search

Advanced search

Quick links