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
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
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
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.
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.
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.
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.
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.
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.
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.
World Health Organization and Food and Agriculture Organization of the United Nations 2006, WHO Press, WorldHealth Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland.
Carr AC, Maggini S. Vitamin C and immune function. Nutrients. 2017;9:1211. https://doi.org/10.3390/nu9111211
Hemila H. Vitamin C and infections. Nutrients. 2017;9:339. https://doi.org/10.3390/nu9040339
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.
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.
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.
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.
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.
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.
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.
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
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.
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
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
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.
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.
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.
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.
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.
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.
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
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
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.
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
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.
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
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.
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.
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
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.
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.
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.
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
Authors and Affiliations
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
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
About this article
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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41430-021-01061-7
This article is cited by
-
Mangelernährung in der Inneren Medizin
Die Innere Medizin (2023)