Appendix V – SUMMARY OF TRIALS: TYPE, REGIMEN AND DURATION OF ONS USED – Tables A5.1 to A5.3

Table A5.1 Community studies

Table A5.2 Hospital studies and hospital to community studies

Table A5.3 Studies in children

A variety of different ONS were used in the trials discussed, but in general, liquid multi-nutrient ONS were used.
The duration of supplementation with ONS ranged from 10 days to 18 months (not specified in some trials).
The energy density ranged from 0.85 kcal/ml to 2.5 kcal/ml and protein content ranged from 3.4 g/100 ml to 13 g/100 ml.
Energy intakes from ONS ranged from 400 kcal to 1000 kcal per day and 17 g to 50 g of protein per day.

Table A5.1

Summary of trials: Type, regimen and duration of ONS used – community studies

Trial	Setting	Population	Design	Sample Size	Intervention					Control	Duration
Trial	Setting	Population	Design	Sample Size	ONS Type	ONS regimen	Energy(kcal) per 100ml	Protein(g) per 100ml	Micronutrients	Control	Duration
Allen et al. (2013)¹	Nursing homes*	Older adults with dementia >65y	Prospective controlled crossover study	26	ONS drinks – various	3 x ONS per day on alternate days	130 (average by calculation)	6.3 (average by calculation)	Contains vitamins and minerals	No ONS on alternate days (26)	1 week
Bonnefoy et al. (2003)²	Retirement homes	Frail older people	RCT factorial design	57	1 kcal/ml	2 x 200ml daily given at 10.00 and 16.00 hours Group 1: ONS plus memory Group 2: ONS plus exercise	100	7.5	ONS provided 50% of Recommended Daily Allowances for vitamins and minerals	Placebo in identical packaging, contained no energy, protein or micronutrients Group 3: placebo plus exercise Group 4: placebo plus memory	9 months
Bunout et al. (2001)³	Community (free-living)	Older people	RCT	149	N/R	2 servings soup/porridge-style supplement daily Group 1: ONS plus resistance exercise training Group 2: ONS, no training	400 (per 100g)	13 (per 100g)	Contained 25% of daily vitamin and mineral requirements	Group 3: no ONS, resistance exercise training Group 4: no ONS and no training	18 months
Chew et al. (2021)⁴	Community	Community-dwelling older adults (≥65 years) at medium/high risk of malnutrition	Randomised placebo-controlled trial	811	Liquid HMB ONS (vanilla flavoured, milk-based)	Two servings/day	Per serving: 262 kcal	Per serving: 10.5 g	Vitamin D and Calcium	Placebo supplement + dietary counselling (n =406)	180 days
Edington et al. (2004)⁵	Community (post-discharge from hospital)	Older people malnourished	RCT	100	Various – N/R	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)	Choice offered. Variety of different energy/ protein contents – N/R		N/R. Some known to be nutritionally complete	Standard care	8 weeks
Jobse et al. (2014)⁶	Nursing homes	Nursing home residents, ≥ 65y, with or at risk of malnutrition	RCT- 2 arms (45 ONS, 42 control)	87	2.4 kcal/ml	Intervention group: 2 x 125 ml bottles daily (low volume HPE ONS) (600kcal/day) given between meals or as part of dessert	240	19.2	Contains all essential, minerals, vitamins and trace elements	Usual care (42)	12 weeks
Jayawardena et al. (2024)⁷	Community setting	Malnourished older adults	Randomised controlled trial	42	Powder ONS (reconstituted to drink)	200 mL once daily before bed for 12 weeks	123.5	6	Contains vitamins and minerals	Water (n = 22)	12 weeks
Kim and Lee (2013)⁸	Community (free-living)	Frail older people, ≥ 65y, low socio-economic status	RCT – 2 arms (43 ONS, 44 control)	87	1.0 kcal/ml	Intervention group: 2 x 200ml cans daily (400 kcal/day) in addition to usual diet	100	6.25	Contains vitamins and minerals	Visited monthly – no placebo ONS/counselling but a small gift given. Home healthcare services suspended during trial period.	12 weeks
Lauque et al. (2004)⁹	Geriatric wards and day care centres	Older people with Alzheimer’s disease, at risk of under-nutrition	RCT	91	Various (1-1.5 kcal/ml)	300 – 500 kcal/ day in addition to the patient’s spontaneous food intake	100 – 150	5 – 8	Enriched with vitamins and minerals	Usual care (some patients from the control group who received ONS prescribed during the study not excluded, but ONS) prescription recorded	3 months
Loman et al. (2018)¹⁰	Post-discharge	Older malnourished adults post hospital discharge	Sub-study of RCT (NOURISH trial)	30 (14 intervention, 16 placebo)	Ready-to-drink liquid supplement	2 servings/day (237 mL each), during hospitalisation and up to 90 days post-discharge	147.5	8.4	26 essential vitamins and minerals 1.5 g calcium HMB	Placebo (n =16): Ready-to-drink liquid placebo (20.3 kcal/100 ml)	90 days (diet recalls at weeks 30,60,90)
Manders et al. (2009)¹¹	Residents of care homes for older people	Older people	RDBPCT parallel	176	1 kcal/ml	2 x 125ml dairy drink between meals (250 kcal/ day)	100	3.5	Added vitamins, minerals & trace elements (25-175% of U.S. RDA, enhanced levels of antioxidants)	Placebo drink, no energy, vitamins or minerals. Contained water, cloudifier, thickener, flavouring, colourant and non-calorific sweetener	6 months
Manders et al. (2009)¹²	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	1 kcal/ml	2 x 125ml dairy drink between meals (250 kcal/ day) in addition to usual diet	100	3.5	Added vitamins, minerals & trace elements (25-175% of Dutch RDA, with added antioxidants)	Placebo drink, no energy, vitamins or minerals. Contained water, cloudifier, thickener, flavouring, colourant and non-calorific sweetener	6 months
McMurdo et al. (2009)¹³	Community (admitted to hospital with acute illness). Residents of care homes excluded	Older people, under-nourished	RCT	253	1.5 kcal/ml	2 x 200ml daily	150	10	Nutritionally complete	Control supplement based on skimmed milk containing 200 kcal, 12.4 g protein	4 months
Neelemaat et al. (2012)¹⁴	Community (post hospital discharge)	Mal-nourished elderly (> 60 years) patients, various specialities	RCT	210	1.5 kcal/ ml HP	2 x 200 ml daily. Alongside high energy/protein diet. Also received 400IE vitamin D3 and 500 mg calcium/d	150	6	Nutritionally complete	Usual care	3 months
Norman et al. (2008)¹⁵	Community	Malnourished patients with GI disease	RCT	101	1.5 kcal/ ml HP**	Up to 3 x 200ml daily. Patients advised to drink ONS slowly and in between meals (≥1 h before a meal) (plus standard DC session as per control, contacted once/ month)	150	10	Nutritionally complete	Standard DC session (verbal advice, 45 min) by a registered dietitian. Advised on improving protein and energy intake with normal food. All patients actively contacted once/month.	3 months
Ng et al. (2015)¹⁶	Community (free-living)	Frail older people, ≥ 65y, able to ambulate without personal assistance, identified door-to door using cardiovascular health study (CHS) criteria for frailty	RCT – 5 arms (49 ONS, 50 cognitive, 48 physical, 49 combination, 50 control)	246	1.5kcal/ml	Group 1: 1x 200ml daily with 4.6g fibre (300 kcal/day) plus 29mg iron, 1mg folate, 200mg B6, 200mcg B12, 600mg Calcium and 200 IU Vit D supplements daily. In addition to usual diet Group 2: Physical exercise Group 3: Cognitive training Group 4: Combination of ONS, exercise and cognitive training Group 5: Control group	154	6	ONS nutritionally complete supplement with 4.6g fibre, plus 29mg iron, 1mg folate, 200mg B6, 200mcg B12, 600mg Calcium and 200 IU Vit D supplements daily.	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	24 weeks / 6 months
Parsons et al. (2016)¹⁷	Care homes	Adults aged >50y at risk of malnutrition	Randomised, parallel, open-label trial (53 ONS, 51 control)	104	Range of styles (drinks, soups, puddings, modules), flavours and volumes	Target provision 600kcal and 16g protein daily (87% took ONS with energy density between 1.5-2.4 kcal/ml).	130-450	NR	Some were complete in micronutrients	Dietary advice by dietitian with leaflet at baseline and at week 6. (51)	12 weeks
Payette et al. (2002)¹⁸	Community	Frail, older undernourished people	RCT	83	Various: N/R	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)	Choice offered. Variety of different energy/protein contents – N/R		N/R. Some known to be nutritionally complete	Visited monthly, no advice/ONS	16 weeks
Persson et al. (2007)¹⁹	Community (recruited in hospital, ONS on discharge)	Older people at risk of malnutrition	RCT	108	1.2 kcal/ml or 0.85 kcal/ml	1 – 2 x 200ml 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, eat more snacks between meals)	120 (complete) 85 (in-complete)	5 4	Vitamins D, B6, B12, Folacin, Mg, Ca, Zn + multi vitamin supplement (nutrients as above except Mg, Ca)	Brief written dietary advice	4 months
Price et al. (2005)²⁰	Community, on discharge from hospital (nursing home residents excluded)	Older people, following acute illness	RCT	136	1.5kcal/ml	2 x 200 ml daily	150	12	N/R. Known to be nutritionally complete	Usual care	8 weeks
Smith et al. (2020)²¹	Primary care setting	Free-living older adults (mean age 71.5 ± 10.7 years) with malnutrition	Randomised controlled trial	308	Ready-made liquid (milk-based and non-milk based), 7 flavours	Ad libitum; target: ≥600 kcal & ≥16 g protein/day (250–400 mL/day)	Fortisip: 240 kcal Fortijuice: 150 kcal	Fortisip: 9.6 – 14.4g Fortijuice: 4 g	Vitamins and minerals included	Dietary advice only (n = 154)	12 weeks
Simmons et al. (2015)²²	Long term care facilities	Nursing home/long stay residents, with orders for nutritional supplementation	RCT – 3 arms (52 supplement ONS, 53 snack, 49 control)	154	Various (twice per day morning and afternoon 5 days per week)	Group 1: supplement intervention – liquid and solid supplement options. Group 2: Snack intervention offered variety of foods e.g. yogurts, puddings and beverages (assorted juices and liquid supplements)	NR	NR	NR	Usual care (49)	24 weeks / 6 months
Tan et al. (2021)²³	Post-discharge setting (home/community)	Patients at nutritional risk post–colorectal cancer surgery (NRS 2002 criteria)	Randomised controlled trial	212 (of 232 enrolled)	Ready-to-drink liquid supplement	500 mL/day, free timing (for 3 months post-discharge)	100 cal	4.1g	Contains vitamins and minerals	Dietary advice only (n = 107)	24 weeks / 6 months
Wouters-Wesseling et al. (2002)²⁴	Nursing Homes	Psycho-geriatric patients	RCT	42	1.1 kcal/ ml	2 x 250 ml daily during the day between main meals. Patients were helped and encouraged by nursing staff to drink the ONS (+ regular dietary intake)	109^†	3.4^†	Contained a range of vitamins and minerals	Placebo (2 x 250ml) consisting of water, cloudifier, flavouring and non-caloric sweetener to resemble ONS in taste and appearance. No energy, no vitamins, no minerals	3 months
Zhu et al. (2019)²⁵	Community setting	Community-dwelling Chinese adults ≥65 years with sarcopenia (Asian criteria)	Randomised controlled trial	113	Powder (to be reconstituted), consumed as a drink	2 sachets per day, between meals, for 12 weeks	231 cal/sachet	8.61 g per sachet	Vitamin D, Omega 3, 1.21g HMB	Waitlist control (n =37). The waitlist control group was asked to keep their normal exercise and eating habits for 6 months. After the study, they received the same exercise programme as the intervention groups. Exercise programme alone (n = 40)	12 weeks + 12 weeks follow-up

*The majority of patients were recruited from nursing homes (18/26) others were recruited from hospitals (8/26).
N/R Not reported. *Mean actual duration of supplementation was 99.4 days (range 6–169). **HP ≥ 20% energy from protein.8 †Calculated from the description of the ONS used in the study. Note that actual intake often not recorded, may differ from target level

Table A5.2

Summary of trials: Type, regimen and duration of ONS used – hospital studies and hospital to community studies

Trial	Setting	Population	Design	Sample Size	Intervention ONS Type					Control (n)	Duration
Trial	Setting	Population	Design	Sample Size	Intervention ONS Type	ONS Regimen (+ other care)	Energy (kcal per 100ml)	Protein (g per 100ml)	Micro-nutrients	Control (n)	Duration
Anbar et al. (2013)²⁶	Hospital	Geriatric hip fracture hospitalised patients >65y	RCT – 2 arms	50	1.5 kcal/ml (Ensure Plus) and 1.0 kcal/ml (Glucerna)	Amount adjusted to make up difference between food intake and energy expenditure.	150 and 100	5.7 and 4.2	Complete	Normal diet ± ONS if already prescribed (28)	14 days or admission length
Bos et al. (2001)²⁷	Hospital inpatients	Malnourished older people	Controlled trial	23	N/R	2 units daily (total 400 kcal, 30g protein). Between meals or at bedtime.	N/R	N/R	Contained vitamins and minerals	No ONS, careful nutrition attention (advice on finishing meals)	10 days
Botella-Carretero et al. (2008)²⁸	Hospital (started 48h post-op, continued post-discharge)	Normally/mildly under-nourished older hip fracture patients	RCT (3-arm)	90	Group A: Protein powder Group B: Liquid ONS	Group A: 4 x 10g packets (36g protein, 152 kcal/day) Group B: 2 x 200ml (37.6g protein, 500 kcal/day)	N/R 125	N/R 9.4	N/R	Standard or texture modified diet	From 48h post-op, maintained after discharge
Botella-Carretero et al. (2010)²⁹	Hospital (started pre-op on admission)	Normally/mildly under-nourished older hip fracture patients	RCT	60	1.0 kcal/ml	2 x 200 ml daily	100	10	Full range of vitamins and minerals	No ONS	Up to 23 days
Burden et al. (2011)³⁰	Hospital pre-operative	Elective colorectal cancer patients	RCT	116	1.5 kcal/ml HP ONS	2 x 200 ml daily between meals. Advised on high protein/energy menu.	150	6	Nutritionally complete	Dietary Advice (DA) only	Until discharge
Deutz et al. (2016)³¹ & Zhong et al. (2016)³²	Hospitals and post-discharge	Older, nourished adults hospitalised for CHF, AMI, pneumonia, or COPD	RDBPCT	654	1.4kcal/ml HP-HMB*	2 x 237ml servings/day during hospitalisation and for 90 days post-discharge	136	8.4	Contains essential micronutrients	Placebo (48 kcal, 12g carb, 10mg Vit C, no other nutrients) (326)	Hospital stay + 90 days post-discharge
Feldblum et al. (2011)³³	Hospital and post-discharge	Elderly medical undernourished patients (MNA-SF < 10, or >10% weight loss)	RCT 3-arm	259	Liquid or pudding (1.5 kcal/ml)	Varied per individualised plan (incl. fortified meals/snacks, multivitamin as appropriate)	150	6.5	15% RDI per 237ml pack	Usual care (some received ONS as part of routine care)	6 months
Flodin et al. (2014)³⁴	Hospitals	Elderly hip fracture patients >60y	RCT 3-arm	79	1.5 kcal/ml	Group 3 only: Calcichew D3 + 35mg Risedronate daily for 12m + 2 x 200ml ONS daily (600kcal, 40g protein) for 6m.	150	10	NR	Group 1: Calcichew D3 (1000mg Ca & 800 IU Vit D) for 12m (25) Group 2: Calcichew D3 + Risedronate for 12m (28)	6-12 months
Gariballa et al. (2006, 2007)^35,36,37	Hospital, continued in community	Older people with acute illness	RDBPCT	445 (total across studies)	2.5 kcal/ml, HP†	2 x 200ml daily at 8:00 am and 12:00 noon (+ Normal Hospital Diet)	249*	12.4*	100% RNI for vitamins & minerals for healthy older person	Normal hospital diet + placebo (identical packaging, minimal kcal (60 kcal), no protein/micronutrients)	6 weeks
Gazzotti et al. (2003)³⁸	Hospital, continued in community	Older people at risk of malnutrition	RCT	80	1.0 kcal/ml & 1.5 kcal/ml	2 x 200ml cups daily (1 of each type, total 500 kcal & 21g protein daily) (+ standard diet)	100 & 150	N/R	N/R (Presumed complete)	No nutritional supplementation	2 months
Hegerova et al. (2015)³⁹	Hospital & post-discharge	Acutely ill hospitalized patients >78y	RCT – 2 arms	200	Sipping supplement	ONS given at 14:00 and 19:00 (+ usual diet), providing 600 kcal/d and 20g protein/d.	N/R	N/R	N/R	Standard care (100)	Admission (11±7d) + 1yr follow-up
Kabata et al. (2015)⁴⁰	Hospitals	Pre-op non-malnourished GI cancer patients	Prospective RCT	102	1.5 kcal/ml (Nutridrink Protein)	2 x 200ml daily for 14 days pre-surgery.	150	10	Contains all essential vitamins & minerals	Standard pre-surgery diet; ONS post-op if required (48)	14 days pre-op + 30d post-op follow-up
Lauque et al. (2004)⁹	Geriatric wards & day care	Older people with Alzheimer’s, at risk of undernutrition	RCT	91	Various (1-1.5 kcal/ml)	300-500 kcal/day in addition to spontaneous food intake.	100-150	5-8	Enriched with vitamins and minerals	Usual care (ONS prescription recorded)	3 months
Miller et al. (2006)⁴¹	Hospital & community	Older people at risk of undernutrition with lower limb fracture	RCT	100	1.5 kcal/ml	Volumes prescribed to meet 45% of energy needs (580–800 ml/day). 4 equal doses daily. Group 1: ONS Group 2: ONS + exercise	150	6*	Complete	Group 3: Exercise Group 4: Attention control (tri-weekly visits)	42 days
Neumann et al. (2004)⁴²	Rehabilitation hospital	Older people following hip fracture	RDB, parallel	46	1.1 kcal/ml HP	At least 2 x 227 ml daily.	106*	6.6	Contains vitamins and minerals	Standard ONS (110 kcal, 3.9g protein per 100ml*)	28 days
Rabadi et al. (2008)⁴³	Stroke rehab hospital	Undernourished patients	RDBCT	102	N/R (Intensive)	120 ml dose every 8 hours by mouth + multivitamins with minerals.	200* (per 100ml)	9.2* (per 100ml)	Nutritionally complete	Standard ONS (127 kcal, 5g protein per 100ml)	Admission to discharge
Rufenacht et al. (2010)⁴⁴	Hospital	Undernourished	RT	36	1.5 kcal/ml (Nutridrink)	NT group: Individualised regimen (fortified meals, snacks, ONS) ONS group: 2 x 200 ml ONS daily	150	6	Full range of vitamins, minerals, trace elements	(Not a controlled trial with a non-nutrition control)	10–15 days
Schuetz et al. (2019)⁴⁵	Hospital (Swiss)	Medical inpatients at nutritional risk (NRS 2002 ≥3)	RCT	2088	ONS + food fortification	Tailored to meet protein/calorie goals; ongoing assessment; post-discharge ONS if needed.	N/R	N/R	N/R	Standard hospital food (1038)	Hospital stay + 30-day follow-up
Sanchez-Lara et al. (2014)⁴⁶	Hospital	Malnourished patients with advanced NSCLC on chemo, ≥18y	RCT-2 arms	92	1.3 kcal/ml +EPA	2 x 200ml bottles daily.	150	10	Contains all essential vitamins & minerals	Standard diet (46)	During chemotherapy
Stratton et al. (2006)^47,48,49	Hospital	Patients with fractured neck of femur, at risk of malnutrition	RCT	50	1.5 kcal/ml	Choice of liquid ONS ad libitum.	150	Various	Contained vitamins and minerals	Isoenergetic food snacks (e.g., cakes, biscuits, puddings)	Post-op until discharge

N/R Not reported. †HP ≥ 20% energy from protein. *Calculated from the description of the ONS used in the study. †1 fluid oz = 28.4 ml. Note that actual intake often not recorded, may differ

Table A5.3

Summary of trials: Type, regimen and duration of ONS used – children

Trial	Setting	Population	Design	Sample Size	Intervention ONS Type					Control (n)	Duration
Trial	Setting	Population	Design	Sample Size	ONS Type	ONS Regimen + other care, if provided)	Energy (kcal per 100ml)	Protein (g per 100ml)	Micro-nutrients	Control (n)	Duration
Alarcon et al. (2003)⁵⁰	Community	Picky eaters below 25th percentile WFH (mean 48.5 months)	Multi-centre RCT, open	92	1.0 kcal/ml paediatric supplement (Paediasure)	40 ml/kg/day in addition to diet (+ physician-directed nutritional counselling)	100	2.8	Complete	Physician-directed nutritional counselling without ONS	90 days
Bayram et al. (2009)⁵¹	Hospital	Children with malignant disease undergoing intensive chemo (mean 7.5±3.0y)	Prospective, randomised, open	52	1.25 kcal/ml HP ONS containing EPA (Prosure)	2 x 240 ml cartons daily	125	6.67	Range of vitamins, minerals, anti-oxidants and EPA	No ONS	3 months
Soylu et al. (2008)⁵²	Community	Malnourished children with spastic quadriplegia	2-centre intervention study	45	1–1.5 kcal/ml paediatric supplement (Paediasure/Fortini)	Dietary advice (texture modification) and ONS	100–150	2.8–3.4	Nutritionally complete	No control	6 months

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