Scoping question: Does oral nutritional supplement, dietary advice or mealtime enhancement produce any benefit for older people at risk of undernutrition or who are affected by undernutrition? The full ICOPE guidelines and complete set of evidence profiles are available at: who.int/publications/i/item/9789241550109# Background
Undernutrition is common among older people over 60 years of age. The prevalence of undernutrition in older people living in the community ranges between 1.3% and 47.8% (1)(2)(3)(4)(5). The reported prevalence is much higher in studies from low-and middle-income countries than high-income countries (6).
Several observational studies have investigated adverse health outcomes in undernourished older people. These have reported strong associations between undernutrition and premature mortality, poor quality of life and reduced functional ability. A recent systematic review of prospective studies from high-income countries reported a strong association between undernutrition and subsequent mortality in older people (7). In another review of longitudinal studies, undernourished older people were found to be twice as likely to experience a poor quality of life than their normally nourished counterparts (8). Other studies have found that older people who report (unintentional) weight loss have a higher risk of developing limitations in basic activities of daily living (ADLs) such as bathing, eating and dressing (9)(10)(11)(12). In a three-year longitudinal study, low body mass index (BMI) was a moderate risk factor for the onset of ADL limitations (13).
Despite the high prevalence of undernutrition reported in population studies, nutritional trials targeting community-dwelling older people are limited. Earlier systematic reviews found that nutritional interventions produced some clinical benefits, including weight gain, albeit the data were less conclusive for improvements in functional outcomes (14). Results from a meta-analysis examining the effect of dietary advice in older persons at risk of undernutrition showed a significant increase in energy and protein intake, and body weight, but no significant effect on physical function or mortality. Most studies included in these reviews recruited healthy older people or older people living in long-term care or admitted to hospital. The effects of nutritional interventions in older people living in the community who are undernourished or at risk of undernutrition therefore remain unclear. This current review was undertaken systematically to review and analyse published reviews and randomized controlled trials, and to summarize the evidence for formulating recommendations for the prevention and management of undernutrition among older people in community and primary care settings.

# ICOPE guidelines -World Health Organization

# Search strategy
An independent search for systematic reviews and clinical trials was performed in September 2015 using the Ovid MEDLINE, Embase and PsycINFO electronic databases. The detailed search strategy is listed in Annex 1.

# List of systematic reviews and trials identified by the search process
Included reviews in GRADE 1 analysis and considered for recommendations (14)(15)(16):
IMPORTANT CI: confidence interval; MD: mean difference; RR: relative risk; SMD: standardized mean difference a. Risk of bias: downgraded once as information on blinding procedure was unclear in four included trials and information on incomplete data was not described in three trials. b. Risk of bias: downgraded once as information on allocation concealment method was unclear in two trials and information on incomplete data was unclear in two trials. c. Risk of bias: downgraded once as information on allocation concealment method was unclear in three trials and information on incomplete data was unclear for two included trials. d. Risk of bias: downgraded once as information on allocation concealment method was unclear in seven trials and analysis was not performed on an intention-to-treat principle in two trials. e. Inconsistency: downgraded once as substantial heterogeneity was observed in the meta-analysis: Tau2 = 4.66;
Chi2 = 42.20, df = 9 (P < 0.00001). No subgroup analysis was performed and we were not able to explain the heterogeneity. f. Risk of bias: downgraded once as information on allocation concealment was unclear in four trials and information on incomplete data was unclear in two trials. g. Inconsistency: downgraded once as moderate heterogeneity was observed in the meta-analysis: Chi2 = 15.39, df = 5 (P = 0.009); I2 = 68%. No subgroup analysis was performed and we were not able to explain the heterogeneity. h. Risk of bias: downgraded once as allocation concealment was unclear in three trials and information on incomplete data management was unclear in two trials. i. Inconsistency: moderate heterogeneity: Chi2 = 6.89, df = 3 (P = 0.08); I2 = 56%; however, P value was not less than 0.05. j. Risk of bias: downgraded once as allocation concealment was unclear in three trials and outcome assessor was not masked in three trials. k. Risk of bias: downgraded once as allocation concealment was unclear in one trial and outcome assessor was not masked in another trial. l. Imprecision: downgraded once as small sample size was smaller than 200. m. Risk of bias: downgraded once as allocation concealment was unclear in two trials and outcome assessor was not masked in two trials. In on trial, analysis was not based on intention-to-treat principle. n. Imprecision: downgraded once as sample size was small.

# ICOPE guidelines -World Health Organization
IMPORTANT CI: confidence interval; MD: mean difference; RR: relative risk; SMD: standardized mean difference Full details of the trials cited in the footnotes below that were included for further analysis (78)(79)(80) are listed sequentially on pages 25-28, Refences; details of the studies that were not included are listed alphabeticallyreferences i-liv on pages 28-30). a. Risk of bias: downgraded once as allocation was not concealed in four trials and information on allocation concealment was unclear in 18 trials. Further, outcome assessors were not masked in 13 trials, and in 16 trials, the procedure was unclear. b. Twenty-two trials that recruited older persons at risk of undernutrition were included in GRADE table 2 (17, 21, 23, 26, 28-30, 33, 39, 43, 44, 54, 55, 59-63, 68, 69, 78, 79), of which five were conducted in a community setting (17,21,23,26,28). c. Risk of bias: downgraded once as allocation concealment method was unclear in four trials, outcome assessor was not masked in three trials and unclear in others. Further analysis was based on intention-to-treat principle in five trials. d. Thirty-four trials included undernourished older persons (18, 19, 22, 24, 25, 27, 31, 32, 34-38, 40-43, 45-53, 56-58, 64-67, 80), of which seven were conducted in a community setting (18-20, 22, 24, 25, 27). e. Risk of bias: downgraded once as allocation was not concealed in three trials and unclear in another 13 trials. Further, outcome assessors were not masked in nine trials and procedure was unclear in other 13 trials. Only six trials adequately provided information on incomplete data. f. Risk of bias: downgraded once as allocation concealment was unclear in 23 trials and allocation was not concealed in four trials. In 25 trials, the procedure of masking outcome assessor was unclear. Further information on incomplete data was adequately described in only 11 trials. g. Inconsistency: downgraded once as substantial heterogeneity was observed: Tau2 = 3.11; Chi2 = 292.00, df = 41 (P  75%). No subgroup analysis was conducted to explore the heterogeneity, and we were not able to explain the heterogeneity. h. Risk of bias: downgraded once as outcome assessor was not masked in three trials and procedure was unclear in another nine trials. Further, information on incomplete data was not described adequately in five trials, and inclusion of incomplete data in the analysis was unclear in three trials. i. Inconsistency: downgraded once as considerable heterogeneity was observed: Chi2 = 173.55, df = 14 (P < 0.00001); I2 = 92%. No further subgroup analysis was conducted to explore the heterogeneity, and we were not able to explain the heterogeneity. j. Risk of bias: downgraded once as allocation concealment was unclear in 13 trials and not concealed in another three trials. Information on incomplete data was not adequately presented in seven trials, and only one trial masked assessors in the outcome assessment. k. Inconsistency: downgraded once as moderate heterogeneity was observed: Chi2 = 63.12, df = 26 (P < 0.0001); I2 = 59%. No further subgroup analysis was conducted to explore the heterogeneity, and we were not able to explain the heterogeneity. l. Risk of bias: downgraded once as allocation concealment was unclear in six trials and the procedure for masking outcome assessor was unclear in three trials. m. Risk of bias: downgraded once as allocation concealment was unclear in three trials, and outcome assessors were not masked in two trials. Information on incomplete outcome data or intention-to-treat was not adequately described in three trials. n. Risk of bias: downgraded once as allocation concealment was unclear in three trials, and outcome assessors were not masked in three trials. In one trial, information on incomplete data was not adequately described, and in another trial, the analysis was not based on intention-to-treat principle. o. Risk of bias: downgraded once as allocation concealment was unclear in two trials and outcome assessors were not masked in another two trials. Four trials reported incomplete data and did not perform the final analysis in intention-to-treat principle. p. Risk of bias: downgraded once as allocation concealment was unclear and the outcome assessor was not masked in one trial. q. Imprecision: downgraded once as the sample size was small. r. Risk of bias: downgraded once as allocation concealment was unclear in one trial, and outcome assessors were not masked in two trials. s. Imprecision: downgraded once as the sample size was smaller than 200 participants. a. Indirectness: downgraded once as comparison groups were not identical. b. Imprecision: downgraded once as confidence interval for treatment effect was wide. c. Risk of bias: downgraded once as allocation concealment and the procedure for masking the outcome assessor were unclear in one trial and the outcome assessor was not masked in another trial. d. Imprecision: downgraded once as sample size of the trial was small (fewer than 200 participants). e. Risk of bias: downgraded once as allocation was not concealed in one trial and was unclear in another two trials. Information on the procedure for masking the outcome assessor was not adequately described in two trials, and information on incomplete data was unclear in three trials. f. Risk of bias: downgraded once as allocation was not concealed in two trials and was unclear in another two trials. Outcome assessors were not masked in two trials. g. Inconsistency: not downgraded as P value was not significant for Chi 2 test for heterogeneity: Chi 2 = 2.59, df = 1 (P = 0.11); I 2 = 61%. h. Imprecision: downgraded once as small size was small (fewer than 200 participants).

# ICOPE guidelines -World Health Organization

# ICOPE guidelines -World Health Organization

# Evidence-to-recommendations table Problem Explanation
Is the problem a priority?
No Uncertain  Undernutrition is a preventable and reversal condition in older people. The prevalence of undernutrition in older people living in the community ranges between 1.3% and 47.8%; it is much higher in low-and middle-income countries than in high-income countries.

# Benefits and harms Explanation
Do the desirable effects outweigh the undesirable effects?

# Yes No Uncertain
There is adequate, moderate-quality evidence to suggest that oral nutritional supplement (ONS) with or without dietary advice improves the nutritional status of undernourished older people. Four trials examined the benefit of ONS for undernourished older people in community settings. Data on weight gain reported as an outcome was pooled in the meta-analysis.
Overall, the pooled treatment effect was in favour of the ONS group (mean difference 3.17 P < 0.01). In addition, 14 trials from hospital or long-term care settings that examined the benefit of ONS reported significant reductions in mortality and increased weight gain in the intervention groups compared with usual care or placebo.
There is adequate, low-quality evidence to suggest that ONS with or without dietary advice may improve the nutritional status of older people at risk of undernutrition. Fifteen trials that investigated the benefit of ONS in hospital or long-term care settings reported significant improvements in body weight. A further seven trials showed a significant improvement in hand grip strength. However, trials from community settings showed no benefit of ONS for older people at risk of undernutrition in either improving body weight or reducing mortality.
Outcomes related to functional status were reported in many trials. Improvements in activities of daily living were assessed in 12 studies; however, the results in only three trials achieved statistical significance. Health-related quality of life was measured in 17 studies. There was a statistically significant benefit in favour of the ONS intervention group in only two of these.

# Equity Explanation
Would the option improve equity in health?
The GDG strongly believes that this recommendation will increase equity in health.

# ICOPE guidelines -World Health Organization

# Guideline development group recommendation and remarks Recommendation
Oral supplemental nutrition with dietary advice should be recommended for older people affected by undernutrition.

# Quality of the evidence: Moderate
Strength of the recommendation: Strong (No recommendation: Dietary advice  received no recommendation because there was limited evidence on its effectiveness among older people at risk of undernutrition or undernourished.)
- The policy priority to support nutritional outcomes among older people must focus on food quality and diversity, and nutrition security. - The nutrition supplement administered aimed to provide between an additional 97 kcal per day and a maximum additional 1200 kcal per day. There was a wide range of types of oral nutritional supplement tested in the included trials (milk, juice, yoghurt, savoury) in different formats (liquid, powder, pudding, pre-thickened) and in combination. - The majority of trials administered nutritional supplement with 20 g protein or more per day. Many of these trials mentioned that micronutrients were included in the supplement. - The duration of the nutritional intervention ranged from 10 days to 6 months in trials recruiting (continued next page) ICOPE guidelines -World Health Organization participants in hospital and long-term care settings. Among trials performed in community settings, duration ranged from 3 months to 18 months.
- Specially formulated supplementary foodsin ready-to-eat or in milled forms that are modified in their energy density, protein, fat or micronutrient composition to help meet the nutritional requirements of older peopleshould be encouraged. - Physical, functional, psychological and social factors that predispose older people to undernutrition should be identified and remedied. - Careful assessment of undernutritionincluding functional, anthropometric, biochemical and clinical assessmentsshould be considered by trained health-care professionals for older people at risk from or suspected of undernutrition. - Nutrition assessment should be an integral part of primary care for older people.
- A social environment that promotes increased food intake for older people with or at risk of undernutrition could be encouraged. - Encouraging all older people at risk of undernutrition to consume oral nutritional supplement (particularly in liquid or powder form) may be unacceptable in some communities. Other strategies such as dietary advice or a nutritional-education programme could be considered. - Although there is no direct evidence for the benefit of dietary advice, guidance on measures to supplement the calorific content in a normal diet should be encouraged when possible. - The older person's tastes and preferences should be considered when administering oral nutritional supplements to improve adherence. - Greater research and clarity is required for the best quality and quantity of oral nutritional supplementation. - The limited number of studies from low-and middle-income countries mean generalizability warrants consideration. - The GDG decided not to issue a stand-alone recommendation for mealtime interventions (including family-style meals and social dining) due to the generic nature of the intervention.
ICOPE guidelines -World Health Organization