Appendix III – SUMMARY OF TRIALS: SETTING, POPULATION, INTERVENTION & OUTCOME – Tables A3.1 to A3.4
Table A3.1 Community studies
Table A3.2 Hospital and hospital to community studies
Table A3.3 Studies undertaken in children
Table A3.4 Studies of EPA-enriched ONS in cancer patients
The studies listed here are key individual trials that have been mentioned within the text to illustrate specific points; therefore, this list is not an exhaustive list of all trials using ONS. For example, studies which have been included in key systematic reviews and meta-analyses have not been listed here.
For trials up to 2002, see Stratton et al. (2003)1. Key systematic reviews and meta-analyses include: Stratton et al. (2003)1,
Langer et al. (2003)2, Stratton et al. (2005)3, Milne et al. (2005, 2006 & 2009)4-6, NICE (2006)7, Elia et al. (2006)8, Lidder et al. (2009)9, Cawood et al. (2012)10, Burden et al. (2012)11, Geeganage et al. (2012)12, Stratton et al. (2013)13, Allen et al. (2013)14, Smyth et al. (2014)15, Collins et al. (2015)16, Liu et al. (2015)17, Francis et al. (2015)18.
Table A3.1
Summary of trials: setting, population, intervention, and outcome – community studies
| Trial | Setting | Population | Design | Sample size | Intervention (n) | Control (n) | Duration | Outcome |
|---|---|---|---|---|---|---|---|---|
| Allen et al. (2013)19 | Nursing homes* (18/26) + hospitals (8/26) | Older adults with dementia >65y | Prospective controlled crossover study | 26 | ONS on alternate days (26) | No ONS on alternate days (26) | 1 week | Nutritional Significantly more energy consumed on intervention days compared to control days (p <0.001). No significant difference between energy consumed from food on intervention days compared to paired control days (p = 0.641). 55.8% of patients met their caloric goals on intervention days, compared to 17.3% on their adjacent control day (p <0.0001). Significantly more total protein consumed on intervention days vs. control days (p <0.0001). No difference in protein intake from food on intervention vs. control days (p = 0.576). On intervention days RDA for protein was more frequently met compared to on control days (p <0.0001) Clinical NR Functional NR Economic NR |
| Bonnefoy et al. (2003)20 | Retirement homes | Frail older people | RCT factorial design | 57 | 2 x 200 ml daily given at 10.00 & 16.00 hours Group 1 – ONS plus memory Group 2 – ONS plus exercise |
Placebo in identical packaging, contained no energy, protein or micronutrients Group 3 – placebo plus exercise Group 4 – placebo plus memory |
9 months | Nutritional Increase in BMI at 3 and 9 months with ONS (p = 0.004, p = 0.007 respectively) Trend towards increase in FFM in ONS group and decrease in placebo group at 3 and 9 months Functional ONS improved muscle power at 3 months (+ 56.8%, p = 0.03) Improved 5-time chair rise with exercise at 9 months (p = 0.014) but no significant effect on muscle function or nutritional status at 3 or 9 months |
| Bunout et al. (2001)21 | Community-dwelling (free-living) | Older people | RCT | 149 | Two servings soup/ porridge-style supplement daily Group 1 – ONS plus resistance exercise training Group 2 – ONS, no training Group 3 – no ONS, resistance exercise training |
Group 4 – no ONS, no training | 18 months | Nutritional No change in body weight or FFM, fat mass increased in all groups. Bone mineral density decreased less in ONS groups than in trained groups (p < 0.01) Functional ADL remained constant in ONS groups and decreased in non-ONS groups. Exercise had no effect Mini-mental scores increased in all groups, no differences among groups No effect of ONS on walking capacity, muscle strength and maximal inspiratory pressure |
| Edington et al. (2004)22 | Community (post-discharge from hospital) | Older people, malnourished | RCT | 100 | Intakes between 600 kcal and 1000 kcal/day prescribed in order to achieve a weight gain of at least 0.5 kg/ week (plus telephone contact by dietitian) | Standard care | 8 weeks* | Nutritional Higher energy intake at week 12 (p = 0.041) Improved nutritional status (BMI, weight and TSFT) between baseline and 24 weeks in ONS group but no significant difference between groups Functional Improvement in hand-grip strength at 8 weeks in ONS group (p = 0.04) (not sustained), trend towards significance at 8 weeks between groups Fewer mobility problems in ONS vs control group at 24 weeks (p = 0.022) |
*Mean actual duration of supplementation was 99.4 days (range 6–169).
| Trial | Setting | Population | Design | Sample Size | Intervention (n) | Control (n) | Duration | Outcome |
|---|---|---|---|---|---|---|---|---|
| Chew et al. (2021)23 | Community | Community-dwelling older adults (≥65 years) at medium/high risk of malnutrition | Randomised placebo-controlled trial | 811 | ONS with HMB + dietary counselling (n=405) | Placebo supplement + dietary counselling (n =406) | 180 days | Nutritional Higher proportion met composite outcome (33.4% vs. 8.7%, p <0.001); greater improvements in weight, BMI, MUAC, nutritional status, and energy/protein intake Functional Greater improvements in leg and handgrip strength, and calf circumference. Economic NR |
| de Luis et al. (2018)24 | Usual clinical practice (multicentre, outpatient) | Older adults >65 years, undernourished or at nutritional risk (NRS ≥3), with multimorbidity (68%) | Observational, prospective, open-label | 235 (148 per protocol) | HP-HMB ONS twice daily (n = 148, ≥75% compliance) | No control group | 12 weeks | Nutritional Significant increase in weight (+2.1 kg), BMI (+0.8), and reduction in NRS score, all p <0.001 Functional Improved activities of daily living (Katz index) and QoL (EQ-5D), all p <0.001 Economic NR |
| Jayawardena et al. (2024)25 | Community setting | Malnourished older adults | Randomised controlled trial | 42 | ONS (200mL, 247kcal per serving) (n=20) | Water (n=22) | 12 weeks | Nutritional NR Functional Significant improvements in handgrip and knee extension strength (p <0.001), gait speed, Barthel index, PASE score, and IPAQ categories in intervention group compared to control. Economic NR |
| Jobse et al. (2014)26 | Nursing homes | Nursing home residents ≥65y | RCT- 2 | 87 | HP ONS (45) | Usual care (42) | 12 weeks | Nutritional Median ONS intake in the intervention group was 438kcal/d. Significantly higher body weight increases in subjects with high compliance median (+3.0kg) than in those with low compliance (-0.2 kg) p <0.001. Residents with high compliance showed a clear increase of nutritional parameters; 3kg body weight gain, improved BMI by 1.2 kg/m2 and increased MNA-SF score by 2 points. High compliance was more often observed in residents with malnutrition (66.7 vs. 27.3%) and chewing difficulties (77.8% vs. 24.2%) than in those without the conditions. Immobility, depression and presence of gastrointestinal complaints were related to a low compliance. Functional: NR(bold) Economic: NR (bold) |
| Kim and Lee (2013)27 | Community (free-living) | Frail older people ≥65y, low SES | RCT – 2 arms | 87 | ONS + DC? (43) | Monthly visits + small gift; home healthcare suspended (44) | 12 weeks | Nutritional: Improved energy, protein, essential amino acid intake, mean adequate ratio (p≤0.008). Clinical: Increased serum BUN (p=0.011) and estimated creatinine clearance (p=0.018). Functional: Short physical battery stable vs. -12.5% control (p=0.039); gait speed -1.0% vs. -12.5% (p=0.039); timed up and go +7.2% vs. -3.4% (p=0.038). Economic: NR. |
| Loman et al. (2019)28 | Post-discharge | Older malnourished adults post-hospital discharge | Sub-study of RCT (NOURISH trial) | 30 | High protein HMB ONS (14) | Standard care + placebo (16) | 90 days | Nutritional: S-ONS increased energy/protein intake without reducing food intake; higher % met energy (50% vs. 29%) and protein (71% vs. 36%) goals; improved micronutrient intake. Functional: NR. Economic: NR. |
| Lauque et al. (2004)29 | Geriatric wards and day care centres | Older people with Alzheimer’s disease, at risk of undernutrition | RCT | 91 | 300–500 kcal/day in addition to the patients’ spontaneous food intake | Usual care (some patients from the control group who received ONS prescribed during the study not excluded but ONS prescription recorded) | 3 months | Nutritional: Improved energy and protein intakes between baseline and 3 months in the intervention group leading to significant improvement in weight and FFM Functional/Clinical: No difference in dependence, cognitive function or biological markers at 3 months or in fractures, pressure ulcers or hospitalisation at 6-month follow-up |
| Manders et al. (2009)30 | Residents of care homes for older people | Older people | RDBPCT, parallel | 176 | 2 x 125 ml dairy drinks between meals (250 kcal/day) | Placebo drink, no energy, vitamins or minerals. Contained water, cloudifier, thickener, flavouring, colourant and non-calorific sweetener | 6 months | Nutritional: Weight gain, 1.6 kg difference in change (p = 0.035) Increased CC, 0.9 cm difference in change (p = 0.48) Improved plasma vitamin D, B12, B6, homocysteine, folate and methylmalonic acid (p < 0.01) No significant effects on physical performance (e.g. hand-grip strength, ADL), verbal fluency or depression score |
| Manders et al. (2009)31 | Residents of care homes for older people (homes for the elderly n = 3, nursing homes n = 3, mixed homes n = 3) | Older people | RDBPCT, parallel | 176 | 2 x 125 ml dairy drinks between meals (250 kcal/day) in addition to usual diet | Placebo drink, no energy, vitamins or minerals. Contained water, cloudifier, thickener, flavouring, colourant and non-calorific sweetener | 6 months | Nutritional: – Increased intake of vitamins and minerals except vitamin A (p < 0.001) (non-randomised sub-sample n = 66) – Most vitamin deficiencies normalised, most notably vitamin D (10% vs 75% remained deficient in ONS vs placebo group) – Non-significant positive effect on macronutrient intake and body weight. Energy intake decreased to the same extent in both groups – No effect on blood proteins or biochemical indicators of general health |
| McMurdo et al. (2009)32 | Community-dwelling (admitted to hospital with acute illness). Residents of care homes excluded | Older people, undernourished | RCT | 253 | 2 x 200 ml ONS daily | Control supplement based on skimmed milk containing 200 kcal, 12.4 g protein | 4 months | Nutritional: – Weight gain† mean difference of 1.17 kg (95% CI 0.07–2.27, p = 0.04) Functional: – Hand-grip strength¥ mean difference of 1.48 kg (95% CI 0.46–2.50, p = 0.005) – Physical activity (accelerometry)¥ mean difference in % change in vector movement 1.71 (95% CI 0.26–3.17, p = 0.02) – No change to ADL, health-related QOL, falls, rehab input, time spent walking, death, unplanned admissions or other adverse events, trend towards improvement in sit-to-stand test in ONS group |
¥Intention to treat analysis. †Per protocol analysis.
| Trial | Setting | Population | Design | Sample Size | Intervention (ONS) | Control | Duration | Outcome |
|---|---|---|---|---|---|---|---|---|
| Neelemaat et al. (2011)33 | Community (post hospital discharge) | Malnourished elderly (> 60 years) patients, various conditions | RCT | 210 | 2 x 200 ml HP ONS daily plus 500mg Calcium and 400IE vitamin D supplement and DC | Usual care | 3 months | Nutritional: Patients in the intervention group tended to gain more weight than controls (mean difference 1.5 kg, 95% CI -0.2–3.1 ns). A significant increase in weight was demonstrated in the highest body weight category > 63.9 kg (mean difference + 3.4 kg, 95% CI 0.2–6.6). No differences in FFM and hand-grip strength. Compliance with ONS 80%. Functional: A positive though non-significant trend of a reduction in functional limitations for both men and women in intervention group after 3 months (mean difference -0.5, 95% CI -1.0–0.1). No significant improvement seen in physical activities and performance. |
| Neelemaat et al. (2011)34 | (Same study as above) | (Same study as above) | (Same study as above) | (Same study as above) | (Same study as above) | (Same study as above) | (Same study as above) | Cost-effectiveness: Second paper reported significant decrease in functional limitations (mean difference -0.72, 95%CI -1.15 to -0.28) with no difference in costs. |
| Ng et al. (2015)35 | Community (free-living) | Frail older people, ≥ 65y | RCT – 5 arms (49 ONS, 50 cognitive, 48 physical, 49 combination, 50 control) | 246 | ONS (49), ONS with exercise and cognitive training (49) | Usual care (50), Placebos identical in appearance to ONS and vitamin/mineral supplements. Artificially sweetened vanilla flavoured liquid made with water and non-dairy creamer. | 6 months | Nutritional: NR Clinical: No significant difference of IADL-ADL dependency, hospitalization between groups as small numbers and low frequency of occurrence. Functional: Significant reductions in frailty scores were seen in all groups 12 month follow up compared with baseline and control groups- nutritional (odds ratio (OR) 2.98), cognition (OR 2.89), physical (OR 4.05) and combination (OR 5.00) for intervention groups. Significant increase in levels of physical activity also seen in the nutritional intervention arm compared with baseline p <0.01 vs control at 6 and 12 months. Economic: NR |
| Norman et al. (2008)36 | Community | Malnourished patients with GI disease | RCT | 101 | Up to 3 x 200 ml daily. Patients advised to drink ONS slowly and between meals (≥ 1 h before a meal) (plus standard DC session as per control, contacted once per month) | Standard DC session (verbal advice, 45 min) by an RD. Advised on improving protein and energy intake with normal food. All patients actively contacted once per month | 3 months | Nutritional: Higher energy and protein intake in ONS group vs control (p < 0.0001) Functional: Improved hand-grip strength and peak flow in ONS group vs controls (p = 0.002, p = 0.047 respectively). Body weight and BMI increased in both groups. Significantly improved QOL in 4 areas in ONS group vs controls (physical functioning, physical role, general health and vitality, p < 0.05) Clinical: Control patients had more readmissions than ONS group (n = 20 vs n = 10, p = 0.041) |
| Payette et al. (2002)37 | Community | Frail older undernourished people | RCT | 83 | 2 x 235 ml daily. Choice of ONS. Encouraged to attain max tolerable energy intake to gain 0.5 kg body weight per week. Instructed to use ONS and increase overall food intake (plus nutrition counselling by phone every 2 weeks between visits) | Visited monthly, no advice/ONS | 16 weeks | Nutritional: ONS group had higher energy intake (p < 0.001) and weight gain (p < 0.001) No significant differences in other anthropometric indexes, muscle strength or functional measures Clinical: Number of bed disability days significantly increased in control group compared with baseline (p = 0.04), no change in bed disability days seen in ONS group |
| Parsons et al. (2016)38 | Care homes | Adults aged >50 y at risk of malnutrition | Randomised, parallel, open-label trial | 104 | ONS ad libitum (range of styles, flavours, volume, energy density; 1.5-2.4kcal/ml). Target provision 600kcal and 16g protein daily. ONS group also seen by dietitian (53) | Dietary advice by dietitian with leaflet at baseline and at week 6 (51) | 12 weeks | Nutritional: No significant changes in the total intake of energy, protein or other nutrients over time in control group. Total energy and protein intakes were significantly greater in intervention group vs. control group at 12 weeks by 423kcal/day (p<0.001) and 14.7g protein/day (p <0.01). Intakes of many micronutrients were significantly greater in intervention vs. control groups. Body weight increased significantly from baseline in intervention group (p = 0.010), but not in the control group (p > 0.05) but no significant difference between the groups. Clinical: NR Functional: QoL (adjusted for baseline QOL, malnutrition risk, type of care received [nursing or residential]) was significantly higher in the ONS than the dietary advice group (intention to treat analysis at week 12; n = 104). EQ-5D TTO scores (mean ± SE) were 0.50 ± 0.04 vs 0.36 ± 0.05 (p = 0.005), VAS rescaled scores were 0.54 ±0.03 vs 0.046 ± 0.03 (p = 0.006) and VAS scores were 61.3 ± 4.5 vs 54.6 ± 6.3 (p = 0.533) for ONS vs dietary advice respectively. Significantly higher scores for all three measures (TTO [0.611 v 0.425; p = 0.002]; VASr [0.608 v 0.491; p = 0.004]; VAS [66.3 v 57.0; p = 0.027]) according to the per protocol analysis at 12 weeks. Responses to questions about appetite sensations did not differ between groups at any time points except for “fullness” which was experienced in a smaller proportion of subjects in the intervention vs. control group at week 12 (41% vs 70%; p < 0.05). |
| Persson et al. (2007)39 | Community (recruited in hospital, ONS on discharge) | Older people at risk of malnutrition | RCT | 108 | 1–2 x 200 ml daily of a choice of either a complete or an incomplete formula (plus 2 individualised counselling sessions by a dietitian, telephone contact from dietitian at 3 time points, advised to increase fat and eat more snacks between meals) | Brief written DA | 4 months | Nutritional: In both intention to treat and per protocol analyses, ONS group maintained weight while controls lost weight (p < 0.001) Functional: Improved ADL in ONS group in the treated-as-protocol analyses (p < 0.05 between groups) |
| Price et al. (2005)40 | Community, on discharge from hospital (nursing home residents excluded) | Older people following acute illness | RCT | 136 | 2 x 200 ml daily | Usual care | 8 weeks | Nutritional: Higher energy intake in ONS group vs controls (p = 0.022) Functional: Improved hand-grip strength in ONS group vs controls over 12 weeks (p = 0.02), mean increase of 19.9% vs 6.6%; intention to treat analysis 13.9% vs 7.2%, (p = 0.055) |
| Pouysségur et al. (2017)41 | Nursing home (frail elderly) | Malnourished older adults with poor dental health | Economic assessment of RCT | 175 | Solid ONS (Protibis® cookies) | No cookies | 6-week intervention, 18-week observation | Nutritional: NR Functional: NR Economic: Cost savings mainly from reduced hospital stays and medical visits related to falls and infections. Daily savings: €1.52–€2.48 per resident. Reduced nursing staff time by 30 min/day/resident. Intervention cost offset by savings |
| Smith et al. (2020)42 | Primary care setting | Free-living older adults (mean age 71.5 ± 10.7 years) with malnutrition | Randomised controlled trial | 308 | ONS + dietary advice (n = 154) | Dietary advice only (n = 154) | 12 weeks | Nutritional: Greater energy intake (+401 kcal/day), protein intake (+15 g/day) and weight gain (+0.8 kg, p <0.001), improved QoL (index score, p =0.009) Functional: NR Economic: Reduced healthcare use (HCP visits −34%, admissions −50%, LOS −62%), higher satisfaction |
| Simmons et al. (2015)43 | Long term care facilities | Nursing home/long stay residents | RCT – 3 arms (52 supplement ONS, 53 snack, 49 control) | 154 | ONS liquid or solid (52) or Snack (53) | Usual care (49) | 6 months | Nutritional: The ONS intervention group took in an average of 265 calories more per day and the snack intervention group an average of 303 calories more per day than the control group. Neither intervention had a significant effect on body weight, despite positive trends. Clinical: NR Functional: NR Economic: Both interventions were cost effective in increasing caloric intake. Cost effectiveness ratios were 103 kcal per dollar for the supplement intervention and 79kcal per dollar for the snack intervention. |
| Wouters-Wesseling et al. (2002)44 | Nursing homes | Psychogeriatric patients | RCT | 42 | 2 x 250 ml daily during day between main meals. Patients were helped and encouraged by nursing staff to drink the ONS (plus regular dietary intake) | Placebo (2 x 250 ml) consisting of water, cloudifier, flavourant and non-calorific sweetener to resemble ONS in taste and appearance. No energy, no vitamins, no minerals | 3 months | Nutritional: Improved body weight with ONS vs placebo (p = 0.03). Significant improvement in homocysteine, vitamins B1, B6, B12, D, thiamine diphosphate and folic acid levels in ONS group vs placebo group. Functional: No significant change in ADL. |
| Tan et al. (2021)45 | Post-discharge setting (home/community) | Patients at nutritional risk post–colorectal cancer surgery (NRS 2002 criteria) | Randomised controlled trial | 212 (of 232 enrolled) | ONS + dietary advice (n = 105) | Dietary advice only (n = 107) | 3 months | Nutritional: ONS group had significantly higher skeletal muscle index (p =0.037), lower sarcopenia prevalence (28.6% vs 42.1%, p =0.040). Functional: Fewer chemotherapy modifications (21.2% vs 36.8%, p =0.024) such as delay, dose reduction, or termination. No significant effects on weight, QoL, or readmissions. Economic: NR |
| Zhu et al. (2019)46 | Community setting | Community-dwelling Chinese adults ≥65 years with sarcopenia (Asian criteria) | Randomised controlled trial | 113 | Exercise alone (n ≈38); Exercise + nutrition supplementation (n ≈38) | Waitlist control (n ≈37) | 12 weeks + 12-week follow-up | Nutritional: NR Functional: No significant difference in gait speed (primary outcome); both intervention groups showed improved leg strength and chair stand test; combined group showed an increase in muscle mass (not sustained to 24 weeks); improved PA scores. Economic: NR |
Note that actual intake often not recorded, may differ from target level.
Table A3.2
Summary of trials: setting, population, intervention, and outcome – hospital studies and hospital to community
| Trial | Setting | Population | Design | Sample Size | Intervention (ONS) | Control | Duration | Outcome |
|---|---|---|---|---|---|---|---|---|
| Anbar et al. (2013)47 | Hospital | Geriatric hip fracture patients >65 y | RCT – 2 arms (22 intervention, 28 control) | 50 | Normal diet + ONS prescribed according to energy requirements/intake (22) | Normal diet + ONS if already prescribed (28) | 14 days or admission length if earlier | Nutritional The intervention group had a significantly higher mean daily intake of energy and protein vs. control group during the first 11 postoperative days (p = 0.001). The calculated daily energy balance was significantly more positive in the intervention group (p <0.05) from days 3 to 10 of the study. Clinical The total complication rate was significantly lower in the intervention group vs. control group (27.3% vs. 64.3%, p = 0.012). This was mainly due to a reduction in the number of infectious complications in the intervention group (13.6% vs. 50%, p = 0.008). No difference in mortality. Functional NR Economic There was a trend for shorter length of hospitalization in the intervention group (10.1 ±3.2 days vs. 12.5± 5.5 days for the control group, p = 0.06). |
| Bos et al. (2001)48 | Hospital inpatients | Malnourished older people | Controlled trial | 23 | 2 units daily providing total of 400 kcal, 30 g protein. Advised to consume between meals or at bedtime | No ONS, but careful nutrition attention from nursing staff (advice on finishing meals) | 10 days | Nutritional Increased energy and protein intake, (p < 0.005 and p < 0.0002 respectively). Functional FFM and BMI changes between day 7 and 17 (p < 0.02 and p < 0.005 respectively). No significant effect on biological markers or hand-grip strength. |
| Botella-Carretero et al. (2008)49 | Hospital (ONS started 48 h after surgery and continued until after discharge) | Normally nourished or mildly undernourished older hip fracture patients | RCT (3-arm) | 90 | Group A: 4 x 10 g packets protein powder providing 36 g protein and 152 kcal/day dissolved in water, milk or soup Group B: 2 x 200 ml liquid ONS providing 37.6 g and 500 kcal/day |
Standard or texture-modified diet | ONS started 48 hours after operation and maintained after hospital discharge | Nutritional No significant effects on nutritional status (albumin, prealbumin, BMI, tricipital fold or midbrachial circumference). Functional/Clinical No differences in hospital stay, mobilisation, blood transfusions, complications. |
| Botella-Carretero et al. (2010)50 | Hospital (ONS started on admission prior to surgery and continued until discharge) | Normally nourished or mildly undernourished older hip fracture patients | RCT | 60 | 2 x 200 ml liquid ONS providing 40 g protein and 400 kcal/day | Standard or texture-modified diet | ONS started 48 hours after operation and maintained after hospital discharge | Nutritional Larger decrease in serum albumin (p = 0.002) and prealbumin (p = 0.045) in control group after surgery and worse postoperative recovery vs intervention group. No significant effects on anthropometric parameters (BMI, tricipital fold or midbrachial circumference). Compliance with supplement was 52.2±12.1% of prescribed amount daily. Intervention group had significantly higher total energy and protein intake vs control group (p < 0.05). Clinical Non-significant tendency for higher postoperative complication rate in the control group. |
| Burden et al. (2011)51 | Hospital (ONS started on admission prior to surgery and continued until surgery min 10 days) | Elective curative surgery for colorectal cancer | RCT | 116 | 2 x 200 ml HP ONS providing 24 g protein and 600 kcal/day plus DA (n = 54) | DA (n = 62) | > 10 days preoperatively | Nutritional Intervention group had significantly higher total energy intake preoperatively: 1722 (489) kcal/d vs 745 (366), p = 0.001). No difference demonstrated for protein intake preoperatively: intervention group 51.8 (33.6) g vs control group 33.0 (16.0) g, p = 0.157. Full compliance with ONS 72%. No significant benefit of ONS on postoperative complications demonstrated. Subgroup analysis showed significant reduction in surgical site infections (Buzby criteria) in weight-losing patients from intervention group preoperatively (p = 0.034). |
| Feldblum et al. (2011)52 | Hospital and post discharge | Elderly medical undernourished patients (MNA-SF < 10 or > 10% weight loss in previous 6 months) stratified into at risk or undernourished | RCT (3-arm) | 259 | Group 1: in hospital and community treatment Group 2: in hospital treatment Treatment: individualised plans to ensure > 35 kcal/kg/d and 1–1.5 g protein/kg/d using diet and food/ONS supplements |
Group 3: standard in-hospital care | Contact monthly for 6 months | Nutritional Mean change in MNA score significantly higher in group 1 (3.0±2.6) than in groups 2 and 3 (1.8±3.0, p = 0.004). Group 1 gained 0.5± 2.84 kg weight over 6 months vs 0.15±2.72 kg in groups 2 and 3 (ns). Trend towards higher intakes of macronutrients seen in group 1 after 3-month follow-up but not significant. No significant haematological/ biochemical differences seen between groups, apart from significantly fewer patients in group 1 had low albumin levels (< 3.5 g/dl) after 6 months (9.7%) compared with groups 2 and 3 (22.9%, p = 0.03). Functional No significant impact of intervention on functional cognitive or depression status. Lower mortality in group 1 (3.8%) vs groups 2 and 3 (11.8%, p = 0.046). |
| Deutz et al. (2016)53 & Zhong et al. (2016)54 | Hospital stay and post discharge | Older (≥65 years) hospitalised patients with a primary diagnosis of acute myocardial infarction, congestive heart failure, pneumonia or chronic obstructive pulmonary disease and with moderate or severe malnutrition | Prospective DBPC RCT | 652 | Standard care plus ONS (containing high protein beta-hydroxy-beta-methylbutyrate (HP-HMB)) (328) | Standard care plus placebo (324) | 90 days | Nutritional Significant improvements in the experimental group, compared with the control group, observed in: odds of achieving a better SGA nutritional class after 90 days (p = 0.009); day 30 body weight (p = 0.035); serum 25(OH)D concentration at days 30 and 60 (p = 0.035 and p = 0.008 respectively). Clinical There was no significant difference between groups for the primary composite end-point (event of death or nonelective readmission within 90 days of discharge). Ninety-day mortality rate significantly decreased in the experimental group compared with the control group (4.8% vs 9.7%; p = 0.018), but no significant difference was observed between the groups for 90-day readmission rates. The Kaplan-Meier curve for mortality showed significantly greater survival in the experimental group compared with the control group (p = 0.013). No significant effects on mean total LOS found. Functional No significant difference in ADL between groups at all time points. Economic Mean 90-day costs for the experimental group were slightly greater than those for the control group ($22,506/person vs $22,133). Through the 90-day follow-up period, the experimental group gained 0.011 more QALYs than the control group, reflecting the experimental group’s significantly greater probability of survival through 90 days follow-up. The 90-day follow-up period ICER was $33,818/QALY. Estimated lifetime expectancy for the experimental group was greater than that of the control group by 0.71 years. Lifetime ICER was $524/LYS. |
| Flodin et al. (2014)55 | Hospital | Elderly hip fracture hospitalised patients, >60 y | RCT- 3 arms (28 Ca/Vit D + Bisphos, 26 Ca/VitD + Bisphos +ONS, 25 Ca/Vit D) | 79 | ONS group: Calcichew D3 + 35mg risedronate daily 12m + 2 x 200ml daily milk based ONS (26) | Control group: Calcichew D3 (25) | 6-12 m | Nutritional NR Clinical Between baseline and 12 months, the percentage change in total body BMD was -0.02% for the ONS group and -0.9% and -1.6% for the bisphos. and control groups, respectively (p = 0.03). There was a mean increase in serum-25-OHD of between 17 nmol/L and 20 nmol/L in all three groups. Functional NR Economic NR |
| Gariballa et al. (2007)56 | Hospital, continued in the community | Older people with acute illness | RDBPCT | 225 | 2 bottles x 200 ml daily at 8.00 a.m. and 12 noon (plus NHD) | NHD plus placebo (identical to the supplement but contained no protein or micro-nutrients and with a minimal kcal content [60 kcal]) | 6 weeks | Functional Increase in number of patients with no depressive symptoms and decrease in patients with mild or severe depression with ONS compared to placebo (p = 0.007) |
| Gariballa et al. (2007)57 | Hospital, continued in the community | Older people with acute illness | RDBPCT | 225 | 2 x 200 ml daily at 8.00 a.m. and 12 noon (plus NHD) | NHD plus placebo (identical to the supplement but contained no protein or micronutrients and with a minimal kcal content [60 kcal]) | 6 weeks | Functional After adjustment for baseline QOL, age and gender, better QOL score with ONS at 6 months (physical function p = 0.04, physical role p = 0.047, and social function p = 0.05) but not at 6 weeks. Overall QOL scores better at 6 months with ONS (p = 0.003), no significant difference in cumulative change between the two groups. No difference in ADL. |
| Gariballa et al. (2006)58 | Hospital, continued in the community | Older people with acute illness | RDBPCT | 445 | 2 x 200 ml daily at 8.00 a.m. and 12 noon (plus NHD) | NHD plus placebo (identical to the supplement but contained no protein or micronutrients and with a minimal kcal content [60 kcal]) | 6 weeks | Nutritional Improved red-cell folate and plasma vitamin B12 in ONS group compared to decrease seen in controls. At 6 months, no difference between groups in weight, BMI, MUAC, TSFT or transferrin. Clinical Reduced readmission rate (29% vs 40%, p < 0.05) |
| Gazzotti et al. (2003)59 | Hospital, continued in the community | Older people at risk of malnutrition | RCT | 80 | 2 x 200 ml daily (one of each energy density to provide total of 500 kcal and 21 g protein daily) (plus standard diet) | No nutritional supplementation | 2 months | Nutritional MNA scores higher in ONS group vs control group at day 60 (p < 0.01). Spontaneous protein and energy intake higher in ONS group vs controls (p < 0.01). Mean weight loss in controls 1.23±2.5 kg (p = 0.01), ONS groups showed non-significant weight increase 0.28±3.8 kg (p = 0.6). Clinical No difference in LOS or discharge destination. |
| Hegerova et al. (2015)60 | Hospital stay and post discharge | Acutely ill hospitalised older patients, >78 y | RCT – 2 arms (100 ONS plus exercise, 100 standard care) | 200 | ONS plus intense rehabilitation exercise program (100) | standard care (100) | Admission length (11 ± 7d) then follow up 3 monthly for 1 year. | Nutritional The total daily energy and protein intakes were significantly higher in ONS group vs control (p <0.001). Intake of hospital food was not reduced. Both groups experienced decreases in body weight and BMI during the hospital stay but the ONS group started to regain both body weight and BMI immediately after discharge and achieved their original weight by 6 month post discharge. LBM did not change during hospital stay in the intervention group compared to the control group and was only 0.4 kg lower at 3 months as opposed to 3.5 kg lower in the control group. Clinical NR Functional: NR Economic NR |
| Huynh et al. (2014)61 | Hospital | Moderate and severely malnourished patients | RCT- 2 arm (106 ONS, 106 control) | 112 | ONS + DC (104) | Standard diet + DC (103) | 12 weeks | Nutritional Significant increases in energy and carbohydrate intakes at week 12 (560 vs 230 kcal) in intervention group vs control (p <0.05). At week 12 ONS significantly increased weight compared to control (2.0 vs 0.9kg) (p <0.001) and BMI (0.76 vs 0.37 kg/m2) (p <0.001). Functional Patients who were in the lowest tertile of baseline handgrip strength score in the ONS group had a greater improvement in handgrip strength at week 4 (p = 0.042) compared to the control group. Clinical No significant differences between the groups in Albumin, pre-albumin or CRP after 12 weeks. Economic NR |
| Kabata et al. (2015)62 | Hospital | Preoperative non-malnourished gastrointestinal cancer patients | Prospective RCT – 2 arm (54 ONS, 48 control) | 102 | ONS 14 days pre-surgery (54). ONS post-surgery if required. | Standard diet pre surgery (48). ONS post-surgery if required. | 14 days, followed up 30 days post-surgery. | Nutritional Body weight decreased significantly in the control group (p <0.001) to borderline level of malnutrition, whereas in supplementation group their levels increased. Clinical In postoperative period, patients in control group suffered from significantly higher (p <0.001) number of serious complications compared with patients receiving ONS. Especially wound infections. Levels of albumin and total protein declined significantly (p <0.001) in the control vs the ONS group where they remained stable. Significant increases in median levels of Transferrin (p = 0.032) and TLC (p = 0.05) in the intervention group. Functional NR Economic NR |
| Lauque et al. (2004)29 | Geriatric wards and day care centres | Older people with Alzheimer’s disease at risk of undernutrition | RCT | 91 | 300–500 kcal/day in addition to the patients’ spontaneous food intake | Usual care (some patients from the control group who received ONS prescribed during the study not excluded but ONS prescription recorded) | 3 months | Nutritional Improved energy and protein intakes between baseline and 3 months in intervention group leading to significant improvement in weight and FFM. Functional/Clinical No difference in dependence, cognitive function or biological markers at 3 months or in fractures, pressure ulcers or hospitalisation at 6-month follow-up. |
| Miller et al. (2006)63 | Hospital, continued in the community (on discharge 52 went to rehab programme, 12 to community hospital, 16 to higher level care and 20 returned to pre-injury admission accommodation) | Older people at risk of undernutrition with fall-related lower limb fracture | RCT | 100 | Supplement volumes were prescribed to meet 45% of individual estimated total energy requirements (range 580–800 ml/day). 4 doses of equal volume administered daily plus usual clinical care Group 1: ONS Group 2: ONS plus resistance training exercise Group 3: resistance training exercise |
Group 4 – Attention control (received tri-weekly visits to match the home visits of the active intervention groups; discussions limited to general information, e.g. benefits of regular exercise and nutrient-dense meals) | 42 days | Nutritional Patients in resistance training group lost more weight than those in ONS plus exercise group (p = 0.029). Functional/Clinical No significant difference in quadriceps strength, gait speed, QOL or healthcare utilisation. |
| Neumann et al. (2004)64 | Rehabilitation hospital | Older people following hip fracture | RDB, parallel | 46 | At least 2 x 8 oz (227 ml*) daily | Compared with standard ONS (110 kcal and 3.9 g protein per 100ml†) | 28 days | Nutritional Protein, fibre, calcium, vitamin K and phosphorus intake greater in HP ONS group. Clinical Trend towards shorter rehab LOS but not significant (23 vs 28 days, p = 0.27). |
| Rabadi et al. (2008)65 | Stroke rehabilitation hospital | Under-nourished patients | RDBCT | 102 | 120 ml dose of an intensive ONS every 8 hours by mouth | Standard ONS (127 kcal, 5 g protein). Standard ONS contained 36 mg vitamin C compared with 90 mg in the intensive ONS | From within 72 hours of arrival on unit to discharge | Nutritional Non-significant greater increase in body weight in intensive group. Functional Improved total FIM and motor FIM sub-score (p < 0.001) and 2-minute and 6-minute walk test (p < 0.001) in the intensive ONS group vs controls. Higher % returned home in the intensive group (63% vs 43%, p < 0.05). |
| Rufenacht et al. (2010)66 | Hospital | Under-nourished patients | RT | 36 | NT group – Individualised nutritional plan including fortified diet, snacks and energy-dense ONS ONS group – energy-dense ONS (2 x 200 ml 1.5 kcal/ml 12 g protein), no other advice |
Isoenergetic food snacks, e.g. cakes, biscuits, puddings | Length of hospital stay (10–15 days) | Nutritional Both groups demonstrated significant improvements in both energy intake (p < 0.001) and protein (p < 0.001) intake from baseline. No significant differences seen between groups. Both groups demonstrated improved QOL parameters from baseline to discharge (NT group p < 0.001, ONS group p < 0.003). No significant differences between groups. NT group showed further significant improvement in QOL 2 months post discharge (p = 0.016). |
| Stratton et al. (2006)67
Stratton et al. (2006)68 Stratton et al. (2007)69 |
Hospital | Patients with fractured neck of femur at risk of malnutrition | RCT | 50 | Choice of liquid ONS ad libitum | Usual care | Postoperatively until discharge | Nutritional Significantly greater energy and protein intake with ONS vs snacks. Significantly greater mean total intake of all water-soluble vitamins in ONS group vs snack group. Clinical Significantly fewer patients in ONS group had complications than in snack group (27% vs 58%, p = 0.04). Non-significant reduction in the incidence of specific complications, i.e. infections 17% vs 33% and wound-related complications (poor wound healing, pressure ulcers) 17% vs 38%. |
| Schuetz et al. (2019)70 | Hospital (medical inpatients) | Medical inpatients at nutritional risk (NRS 2002 ≥3), expected stay >4 days | Randomised controlled trial (EFFORT) | 2088 | Individualised nutritional support (n = 1050) | Standard hospital food (n = 1038) | Hospital stay + 30-day follow-up | Clinical Intervention group had fewer adverse clinical outcomes (23% vs 27%, OR 0.79, p =0.023) including mortality, ICU admission, major complications, and readmissions, lower 30 day mortality (7% vs 10%, OR 0.65, p =0.011), no increase in nutritional side effects; improved survival and clinical outcomes. |
| Schuetz et al. (2020)71 | Hospital (Medical inpatients) | Medical inpatients at nutritional risk (NRS 2002 ≥3) | Economic evaluation of RCT (EFFORT) | 2,028 | Individualised nutritional support (n =1015) | Standard hospital food (n =1013) | 30 days post-admission | Nutritional NR Functional Economic: One severe complication: CHF2,675 (2490 €) for one day in ICU. |
| Snider et al. (2015)72 | Hospital (Medicare inpatients with COPD) | Medicare patients aged ≥65 hospitalised with primary COPD | Retrospective cohort with propensity-score matched analysis and instrumental variables | 14,326 matched (ONS vs non-ONS) | Hospital oral nutritional supplementation (ONS) | No ONS hospitalizations (matched) | Hospital stay + 30-day readmission | Nutritional NR Functional Economic |
*1 fluid oz = 28.4 ml. †Calculated from the description of the ONS used in the study. Note that actual intake often not recorded, may differ from target level
Table A3.3
Summary of trials in children: setting, population, intervention, and outcome
| Trial | Setting | Population | Design | Sample Size | Intervention (ONS) | Control | Duration | Outcome |
|---|---|---|---|---|---|---|---|---|
| Alarcon et al. (2003)73 | Community | Mean age 48.5 months (range 36.0–61.0 months) Picky eaters below 25th percentile WFH (children with underlying acute/chronic disease excluded) | Multi-centre randomised, parallel group, open study | 92 | Physician-directed nutritional counselling with ONS | Physician-directed nutritional counselling without ONS | 90 days | Significantly greater increase in WFH percentiles from baseline to day 60 (p = 0.002) and day 90 (p < 0.001) in study group vs controls.
Significantly greater increase in WFH percentiles from baseline to day 90 (p < 0.001) in study group vs controls – Philippines only Significantly greater increases for weight, height, WFH, WFA and HFA percentiles in study group compared to control group at all time points (p < 0.05) except HFA at day 30. Upper respiratory tract infections significantly lower in the study group vs controls (28% vs 51% respectively, p = 0.027). |
| Bayram et al. (2009)74 | Not specified | Mean age 7.5±3.0 years. Children with malignant disease undergoing intensive chemotherapy. | Prospective randomised single centre open label study | 52 | Protein- and energy-dense EPA containing ONS in addition to normal dietary intake (2 x 240 ml/day) | Usual dietary care | 3 months | At 3 months, significantly fewer patients in treatment group showed a loss in body weight (6.1% vs 47.4%, p = 0.001) and BMI (12.1% vs 52.6%, p = 0.002), and a negative deviation in weight percentile (6.1% vs 31.6%, p = 0.021) compared to the control group. After 6 months (n = 23), the % of patients with weight loss was significantly lower in the treatment group vs controls (6.7% vs 50%, p = 0.03). No significant differences in BMI and negative deviation from weight percentile at this time point. At 3 months, the remission rate in the treatment group was significantly greater vs controls (87.9% vs 63.2%, p = 0.036). |
| Soylu et al. (2008)75 | Community | Children with spastic quadriplegia (malnourished) | Un-controlled intervention study | 45 | Nutritional support including DA and ONS | No control group | 6 months | Significant changes in weight, height, MAC, TSFT, weight z-score, WFA, WFH, BMI and number of infections after treatment compared to baseline. |
Table A3.4
Summary of trials of EPA-enriched ONS in cancer patients: design, population, intervention, and outcome
| Trial | Design | Population | Intervention | Control | Duration | Outcome |
|---|---|---|---|---|---|---|
| Fearon et al. (2003)76 | Multi-centre RCT | Advanced pancreatic cancer patients with cachexia | 474 ml EPA-enriched ONS (providing 2.2 g EPA, 620 kcal, 32 g protein and enhanced levels of antioxidants) (n = 95) | 474 ml Isocaloric, isonitrogenous standard ONS (n = 105) | 8 weeks | Significant increase in total (diet plus supplement) energy and protein intake from baseline in experimental group completing 8 weeks (mean 224 kcal, p = 0.001 and 15 g protein/day, p < 0.001) compared to control group increase 68 kcal/day, ns and 6 g protein (p = 0.036). Post hoc analysis demonstrated significant correlation between supplement intake and weight gain in the EPA group (r = 0.5, p < 0.001) and an increase in LBM (r = 0.33, p = 0.036) in the study group that were not seen in the control group. Significant correlation between 8-week plasma EPA level and an increase in weight (r = 0.50, p < 0.001) and LBM (r = 0.51, p < 0.001) were also seen in the study group. Intake of EPA-enriched supplement correlated positively with QOL (EQ-5D index) (r = 0.46, p < 0.001). |
| Guarcello et al. (2007)77 | Blinded RCT | Malnourished patients with lung cancer undergoing chemotherapy | 474 ml EPA-enriched ONS (providing 2.2 g EPA, 590 kcal, 32 g protein and enhanced levels of antioxidants) (n = 46) | 474 ml isocaloric, isonitrogenous standard ONS (n = 105) | 60 days | Significant improvements seen in body weight, oral energy and protein intake from diet seen from baseline (T0) in EPA-enriched ONS group (weight T0: 57.7 kg [42.7–70.6] – end 58.6 kg [46.0–73.0], p < 0.05; kcal intake T0: 1300 kcal [850–1700] – end 2000 [900–3300], p < 0.05; protein intake T0: 40 g [20–55] – end 60 g [35–80], p < 0.05). No differences seen in control group. No between-group comparisons reported. |
| Read et al. (2007)78 | Open label phase II study | Stage IV colorectal cancer patients undergoing chemotherapy | 480 ml EPA-enriched ONS (providing 2.2 g EPA, 0.92 g DHA, 600 kcal, 32 g protein and enhanced levels of antioxidants) (n = 23) | – | 9 weeks | Mean weight increase 2.5 kg seen after 3 weeks (p = 0.03) prior to commencement of treatment; weight was then maintained through course of treatment. No significant increase in LBM seen. |
| Van der Meij et al. (2010)79 | RDBPCT | Stage 3 non-small-cell lung cancer undergoing multi-modality treatment | 480 ml EPA-enriched ONS (providing 2.2 g EPA, 0.92 g DHA, 600 kcal, 32 g protein and enhanced levels of antioxidants) (n = 20) | 400 ml Ensure plus® (n = 20) | 5 weeks | EPA-enriched ONS group demonstrated significant improvements in energy and protein intakes after 4 weeks – 2456 kJ (p = 0.03) and 25.0 g (p = 0.01) respectively. The intervention group demonstrated better weight maintenance (by 1.7 kg, p = 0.04) after 4 weeks and a smaller reduction in LBM (by 1.9 kg, p < 0.05) after 5 weeks compared with control group. |
| Weed et al. (2011)80 | Prospective observational study | Perioperative head and neck small-cell cancer (SCC) (grade II+) patients with weight loss < 5% in previous 6 months | 480 ml EPA-enriched ONS (providing 2.2 g EPA, 0.92 g DHA, 600 kcal, 32 g protein and enhanced levels of antioxidants) (n = 38) | – | Approx. 4 weeks | 70% maintained or gained weight prior to surgery (mean + 0.71 kg), with 57% continuing to maintain or gain weight during hospital admission (mean + 0.66 kg). There was a statistically significant increase in LBM (+ 3.21 kg over the course of the study (p < 0.01) and a reduction in fat mass by 3.19 kg (p < 0.001). |