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Meta-Analysis: Protein and Energy Supplementation in Older People

Anne C. Milne, MSc; Alison Avenell, MD; and Jan Potter, MBChB
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From University of Aberdeen, Aberdeen, Scotland, United Kingdom, and Wollongong Hospital, Sydney, Australia.

Acknowledgments: The authors thank the authors who provided further information about the trials; Craig Ramsay and Jonathan Cook, for statistical advice; and Dr. Helen Handoll, who was also involved in the data extraction of trials.

Grant Support: By the Medical Research Council, United Kingdom; Chief Scientist Office of the Scottish Executive Health Department, United Kingdom; and the Student Awards Agency for Scotland, United Kingdom.

Potential Financial Conflicts of Interest: Dr. Potter was principal investigator for a trial included in the review (61).

Requests for Single Reprints: Anne C. Milne, MSc, Health Services Research Unit, Polwarth Building, University of Aberdeen, Aberdeen AB25 2ZD, Scotland, United Kingdom; e-mail, a.c.milne@abdn.ac.uk.

Current Author Addresses: Ms. Milne and Dr. Avenell: Health Services Research Unit, Polwarth Building, University of Aberdeen, Aberdeen AB25 2ZD, Scotland, United Kingdom.

Dr. Potter: Acute Geriatric Service, Wollongong Hospital, Level 4 Block C LMB 8808, South Coast Mail Centre 2521, UNSW, Sydney 2052, Australia.

Ann Intern Med. 2006;144(1):37-48. doi:10.7326/0003-4819-144-1-200601030-00008
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Background: Protein and energy undernutrition is common in older people, and further deterioration may occur during illness.

Purpose: To assess whether oral protein and energy supplementation improves clinical and nutritional outcomes for older people in the hospital, in an institution, or in the community.

Data Sources: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, HealthStar, CINAHL, BIOSIS, and CAB abstracts. The authors included English- and non–English-language studies and hand-searched journals, contacted manufacturers, and sought information from trialists. The date of the most recent search of CENTRAL and MEDLINE is June 2005.

Study Selection: Randomized and quasi-randomized, controlled trials of oral protein and energy supplementation compared with placebo or control treatment in older people.

Data Extraction: Two reviewers independently assessed trials for inclusion, extracted data, and assessed trial quality. Differences were resolved by consensus.

Data Synthesis: Fifty-five trials were included (n = 9187 randomly assigned participants). For patients in short-term care hospitals who were given oral supplements, evidence suggested fewer complications (Peto odds ratio, 0.72 [95% CI, 0.53 to 0.97]) and reduced mortality (Peto odds ratio, 0.66 [CI, 0.49 to 0.90]) for those undernourished at baseline. Few studies reported evidence that suggested any change in mortality, morbidity, or function for those given supplements at home. Ten trials reported gastrointestinal disturbances, such as nausea, vomiting, and diarrhea, with oral supplements.

Limitations: The quality of most studies, as reported, was poor, particularly for concealment of allocation and blinding of outcome assessors. Many studies were too small or the follow-up time was too short to detect a statistically significant change in clinical outcome. The clinical results are dominated by 1 very large recent trial in patients with stroke. Although this was a high-quality trial, few participants were undernourished at baseline.

Conclusions: Oral nutritional supplements can improve nutritional status and seem to reduce mortality and complications for undernourished elderly patients in the hospital. Current evidence does not support routine supplementation for older people at home or for well-nourished older patients in any setting.


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Figure 1.
Flow chart for study selection.

*Main reasons were study not randomized, intervention did not meet inclusion criteria (nasogastric feeding, high-protein vs. low-protein, early vs. late introduction of feeding, and immunomodulatory supplements), or participants did not fit the inclusion criteria (too young and patients with cancer).

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Figure 2.
Meta-analysis of mortality.

FOOD = Feed Or Ordinary Diet; OR = odds ratio.

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Figure 3.
Analysis of mortality data by nutritional status.

FOOD = Feed Or Ordinary Diet; OR = odds ratio.

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Figure 4.
Analysis of participants developing complications.

FOOD = Feed Or Ordinary Diet; OR = odds ratio.

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Figure 5.
Meta-analysis of percentage weight change.

WMD = weighted mean difference.

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Appendix Figure 1. OR = odds ratio.
Funnel plot.
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Appendix Figure 2. FOOD = Feed Or Ordinary Diet; WMD = weighted mean difference.
Meta-analysis of length of stay (LOS).
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Appendix Figure 3. WMD = weighted mean difference.
Meta-analysis of percentage of arm muscle circumference change (AMCC).
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