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Meta-Analysis
. 2024 Feb 12;2(2):CD003216.
doi: 10.1002/14651858.CD003216.pub3.

Nutritional interventions for preventing and treating pressure ulcers

Gero Langer  1 , Ching Shan Wan  2   3 , Astrid Fink  4 , Lukas Schwingshackl  5 , Daniela Schoberer  6
Affiliations
Meta-Analysis

Nutritional interventions for preventing and treating pressure ulcers

Gero Langer et al. Cochrane Database Syst Rev. .

Abstract

Background: Pressure ulcers are localized injuries to the skin or the underlying tissue, or both, and are common in older and immobile people, people with diabetes, vascular disease, or malnutrition, as well as those who require intensive or palliative care. People with pressure ulcers often suffer from severe pain and exhibit social avoidance behaviours. The prevention and treatment of pressure ulcers involves strategies to optimize hydration, circulation, and nutrition. Adequate nutrient intake can reduce the risk factor of malnutrition and promote wound healing in existing pressure ulcers. However, it is unclear which nutrients help prevent and treat pressure ulcers. This is an update of an earlier Cochrane Review.

Objectives: To evaluate the benefits and harms of nutritional interventions (special diets, supplements) for preventing and treating pressure ulcers in people with or without existing pressure ulcers compared to standard diet or other nutritional interventions.

Search methods: We used extensive Cochrane search methods. The latest search was in May 2022.

Selection criteria: We included randomized controlled trials (RCTs) in people with or without existing pressure ulcers, that compared nutritional interventions aimed at preventing or treating pressure ulcers with standard diet or other types of nutritional interventions.

Data collection and analysis: We used standard Cochrane methods. Our primary outcome for prevention studies was the proportion of participants who developed new (incident) pressure ulcers. For treatment studies, our primary outcomes were time to complete pressure ulcer healing, number of people with healed pressure ulcers, size and depth of pressure ulcers, and rate of pressure ulcer healing. Secondary outcomes were side effects, costs, health-related quality of life and acceptability. We used GRADE to assess certainty of evidence for each outcome.

Main results: We included 33 RCTs with 7920 participants. Data for meta-analysis were available from 6993 participants. Pressure ulcer prevention Eleven studies (with 12 arms) compared six types of nutritional interventions for the prevention of pressure ulcers. Compared to standard diet, energy, protein and micronutrient supplements may result in little to no difference in the proportion of participants developing a pressure ulcer (energy, protein and micronutrient supplements 248 per 1000, standard diet 269 per 1000; RR 0.92, 95% CI 0.71 to 1.19; 3 studies, 1634 participants; low-certainty evidence). Compared to standard diet, protein supplements may result in little to no difference in pressure ulcer incidence (protein 21 per 1000, standard diet 28 per 1000; RR 0.75, 95% CI 0.49 to 1.14; 4 studies, 4264 participants; low-certainty evidence). The evidence is very uncertain about the gastrointestinal side effects of these supplements (protein 109 per 1000, standard diet 155 per 1000; RR 0.70, 95% CI 0.06 to 7.96; 2 studies, 140 participants, very low-certainty evidence). The evidence is very uncertain about the effects of protein, arginine, zinc and antioxidants; L-carnitine, L-leucine, calcium, magnesium and vitamin D; EPA, GLA and antioxidants; disease-specific supplements on pressure ulcer incidence when compared to standard diet (1 study each; very low-certainty evidence for all comparisons). Pressure ulcer treatment Twenty-four studies (with 27 arms) compared 10 types of nutritional interventions or supplements for treatment of pressure ulcers. Compared to standard diet, energy, protein and micronutrient supplements may slightly increase the number of healed pressure ulcers (energy, protein and micronutrients 366 per 1000, standard diet 253 per 1000; RR 1.45, 95% CI 1.14 to 1.85; 3 studies, 577 participants, low-certainty evidence). The evidence is very uncertain about the effect of these supplements on gastrointestinal side effects. Compared to standard diet, the evidence is very uncertain about the effect of protein, arginine, zinc and antioxidant supplements on pressure ulcer healing (pressure ulcer area: mean difference (MD) 2 cm² smaller, 95% CI 4.54 smaller to 0.53 larger; 2 studies, 71 participants, very low-certainty evidence). The evidence on side effects of these supplements is very uncertain. Compared to standard diet, supplements with arginine and micronutrients may not increase the number of healed pressure ulcers, but the evidence suggests a slight reduction in pressure ulcer area (MD 15.8% lower, 95% CI 25.11 lower to 6.48 lower; 2 studies, 231 participants, low-certainty evidence). The evidence is very uncertain about changes in pressure ulcer scores, acceptability, and side effects of these supplements. Compared to placebo, collagen supplements probably improve the mean change in pressure ulcer area (MD 1.81 cm² smaller, 95% CI 3.36 smaller to 0.26 smaller; 1 study, 74 participants, moderate-certainty evidence). The evidence is very uncertain about the effect of these supplements on side effects. The evidence is very uncertain about the effects of vitamin C, different doses of arginine; EPA, GLA (special dietary fatty acids) and antioxidants; protein; a specialized amino acid mixture; ornithine alpha-ketoglutarate and zinc supplements on pressure ulcer healing (1 or 2 studies each; very low-certainty evidence).

Authors' conclusions: The benefits of nutritional interventions with various compositions for pressure ulcer prevention and treatment are uncertain. There may be little or no difference compared to standard nutrition or placebo. Nutritional supplements may not increase gastrointestinal side effects, but the evidence is very uncertain. Larger studies with similar nutrient compositions would reduce these uncertainties. No study investigated the effects of special diets (e.g. protein-enriched diet, vegetarian diet) on pressure ulcer incidence and healing.

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Conflict of interest statement

G Langer: no conflict of interest CS Wan: no conflict of interest D Schoberer: no conflict of interest L Schwingshackl: no conflict of interest A Fink: no conflict of interest

Figures

1
1
Risk of bias assessment traffic light plot for individual randomized studies
2
2
Risk of bias summary plot in percentages for individual randomized studies. This review includes 33 studies.
3
3
Risk of bias traffic light plot for cross‐over studies
4
4
Study flow diagram
5
5
Overview of interventions
6
6
Comparison 1. Energy, protein and micronutrients versus standard diets for pressure ulcer prevention, outcome 1: incidence of pressure ulcers
7
7
Comparison 5. Protein supplements versus standard diets for pressure ulcer prevention, outcome 1: incidence of pressure ulcers
8
8
Comparison 5. Protein supplements versus standard diets for pressure ulcer prevention, outcome 2: gastrointestinal side effects
9
9
Comparison 7. Energy, protein and micronutrients versus standard diets for pressure ulcer treatment, outcome 1: number of people healed
10
10
Comparison 8. Protein, arginine, zinc and antioxidants versus standard diets or placebo for pressure ulcer treatment, outcome 1: number of people healed
11
11
Comparison 8. Protein, arginine, zinc and antioxidants versus standard diets or placebo for pressure ulcer treatment, outcome 1: ulcer size (change in pressure ulcer area in cm2)
12
12
Comparison 8. Protein, arginine, zinc and antioxidants versus standard diets or placebo for pressure ulcer treatment, outcome 3: rate of ulcer healing (PUSH score)
13
13
Comparison 9. Arginine and micronutrients versus standard diets or placebo for pressure ulcer treatment, outcome 3: ulcer size (percentage change in pressure ulcer area)
14
14
Comparison 9. Arginine and micronutrients versus standard diets or placebo for pressure ulcer treatment, outcome 6: side effects (at least one adverse gastrointestinal effect)
15
15
Comparison 13. Collagen versus standard diets or placebo for pressure ulcer treatment, outcome 2: rate of ulcer healing (PUSH score)
16
16
Comparison 13: Collagen versus standard diets or placebo for pressure ulcer treatment, Outcome 4: Side effects (at least one adverse gastrointestinal effect)
17
17
Comparison 16. Vitamin C versus placebo for pressure ulcer treatment, outcome 1: pressure ulcers healed
1.1
1.1. Analysis
Comparison 1: Prevention: energy, protein and micronutrients versus standard diet, Outcome 1: Incidence of pressure ulcers
2.1
2.1. Analysis
Comparison 2: Prevention: protein, arginine, zinc and antioxidants versus placebo, Outcome 1: Incidence of pressure ulcers
3.1
3.1. Analysis
Comparison 3: Prevention: L‐carnitine, L‐leucine, calcium, magnesium and vitamin D versus standard diet, Outcome 1: Incidence of pressure ulcers
4.1
4.1. Analysis
Comparison 4: Prevention: EPA, GLA and antioxidants versus standard diet, Outcome 1: Incidence of pressure ulcers
5.1
5.1. Analysis
Comparison 5: Prevention: protein versus standard diet, Outcome 1: Incidence of pressure ulcers
5.2
5.2. Analysis
Comparison 5: Prevention: protein versus standard diet, Outcome 2: At least one adverse gastrointestinal effect
6.1
6.1. Analysis
Comparison 6: Prevention: disease‐specific versus standard diet, Outcome 1: Incidence of pressure ulcers
7.1
7.1. Analysis
Comparison 7: Treatment: energy, protein and micronutrients versus standard diet, Outcome 1: Pressure ulcers healed
7.2
7.2. Analysis
Comparison 7: Treatment: energy, protein and micronutrients versus standard diet, Outcome 2: At least one adverse gastrointestinal effect
8.1
8.1. Analysis
Comparison 8: Treatment: protein, arginine, zinc and antioxidants versus standard diet or placebo, Outcome 1: Pressure ulcers healed
8.2
8.2. Analysis
Comparison 8: Treatment: protein, arginine, zinc and antioxidants versus standard diet or placebo, Outcome 2: Change in pressure ulcer area (cm²)
8.3
8.3. Analysis
Comparison 8: Treatment: protein, arginine, zinc and antioxidants versus standard diet or placebo, Outcome 3: PUSH score
8.4
8.4. Analysis
Comparison 8: Treatment: protein, arginine, zinc and antioxidants versus standard diet or placebo, Outcome 4: At least one adverse gastrointestinal effect
9.1
9.1. Analysis
Comparison 9: Treatment: arginine and micronutrients versus standard diet or placebo, Outcome 1: Pressure ulcers healed
9.2
9.2. Analysis
Comparison 9: Treatment: arginine and micronutrients versus standard diet or placebo, Outcome 2: Change in pressure ulcer area (cm²)
9.3
9.3. Analysis
Comparison 9: Treatment: arginine and micronutrients versus standard diet or placebo, Outcome 3: Change in pressure ulcer area (percentage)
9.4
9.4. Analysis
Comparison 9: Treatment: arginine and micronutrients versus standard diet or placebo, Outcome 4: Change in PUSH score
9.5
9.5. Analysis
Comparison 9: Treatment: arginine and micronutrients versus standard diet or placebo, Outcome 5: DESIGN‐R score
9.6
9.6. Analysis
Comparison 9: Treatment: arginine and micronutrients versus standard diet or placebo, Outcome 6: At least one adverse gastrointestinal effects
9.7
9.7. Analysis
Comparison 9: Treatment: arginine and micronutrients versus standard diet or placebo, Outcome 7: Costs (EUR)
9.8
9.8. Analysis
Comparison 9: Treatment: arginine and micronutrients versus standard diet or placebo, Outcome 8: Acceptability: non adherence
10.1
10.1. Analysis
Comparison 10: Treatment: different doses of arginine, Outcome 1: PUSH score
10.2
10.2. Analysis
Comparison 10: Treatment: different doses of arginine, Outcome 2: At least one side effect
10.3
10.3. Analysis
Comparison 10: Treatment: different doses of arginine, Outcome 3: Acceptability: non adherence
11.1
11.1. Analysis
Comparison 11: Treatment: EPA, GLA and antioxidants versus standard diet, Outcome 1: Pressure ulcers healed
11.2
11.2. Analysis
Comparison 11: Treatment: EPA, GLA and antioxidants versus standard diet, Outcome 2: PUSH score
12.1
12.1. Analysis
Comparison 12: Treatment: protein versus standard diet, Outcome 1: Pressure ulcers healed
12.2
12.2. Analysis
Comparison 12: Treatment: protein versus standard diet, Outcome 2: Pressure ulcer episodes
12.3
12.3. Analysis
Comparison 12: Treatment: protein versus standard diet, Outcome 3: PUSH score
12.4
12.4. Analysis
Comparison 12: Treatment: protein versus standard diet, Outcome 4: Diarrhoea episodes
12.5
12.5. Analysis
Comparison 12: Treatment: protein versus standard diet, Outcome 5: Costs (EUR)
13.1
13.1. Analysis
Comparison 13: Treatment: collagen versus standard diet or placebo, Outcome 1: Change in pressure ulcer area (cm²)
13.2
13.2. Analysis
Comparison 13: Treatment: collagen versus standard diet or placebo, Outcome 2: PUSH score
13.3
13.3. Analysis
Comparison 13: Treatment: collagen versus standard diet or placebo, Outcome 3: DESIGN‐R score
13.4
13.4. Analysis
Comparison 13: Treatment: collagen versus standard diet or placebo, Outcome 4: At least one adverse gastrointestinal effect
14.1
14.1. Analysis
Comparison 14: Treatment: specialised amino acid mixture (arginine‐enriched) versus standard diet or placebo, Outcome 1: PUSH score
14.2
14.2. Analysis
Comparison 14: Treatment: specialised amino acid mixture (arginine‐enriched) versus standard diet or placebo, Outcome 2: At least one adverse gastrointestinal effect
15.1
15.1. Analysis
Comparison 15: Treatment: ornithine alpha‐ketoglutarate versus placebo, Outcome 1: Change in pressure ulcer area (cm²)
15.2
15.2. Analysis
Comparison 15: Treatment: ornithine alpha‐ketoglutarate versus placebo, Outcome 2: Change in pressure ulcer area (percentage)
15.3
15.3. Analysis
Comparison 15: Treatment: ornithine alpha‐ketoglutarate versus placebo, Outcome 3: Side effects
16.1
16.1. Analysis
Comparison 16: Treatment: vitamin C versus placebo, Outcome 1: Pressure ulcers healed
16.2
16.2. Analysis
Comparison 16: Treatment: vitamin C versus placebo, Outcome 2: Change in pressure ulcer area (percentage)
17.1
17.1. Analysis
Comparison 17: Treatment: zinc sulphate versus placebo, Outcome 1: Pressure ulcers healed
17.2
17.2. Analysis
Comparison 17: Treatment: zinc sulphate versus placebo, Outcome 2: Change in pressure ulcer volume (mL)
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    1. ACTRN12605000704695. Early PN trial 2005. http://www.who.int/trialsearch/Trial2.aspx?TrialID=ACTRN12605000704695 2005. [https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=863&sho...]
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Gray 2003a {published data only}
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Gray 2003b {published data only}
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Gray 2003c {published data only}
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Gutman 2019 {published data only}
    1. Gutman JB, Kongshavn PA. Cysteine/cystine-rich undenatured whey protein supplement in patients' pressure ulcers outcomes: an open label study. Journal of Wound Care 2019;28 Suppl 7:S16-S23. - PubMed
Harvey 2016 {published data only}
    1. Harvey SE, Parrott F, Harrison DA, Zia Sadique M, Grieve RD, Canter RR, et al. A multicentre, randomised controlled trial comparing the clinical effectiveness and cost-effectiveness of early nutritional support via the parenteral versus the enteral route in critically ill patients (CALORIES). Health Technology Assessment 2016;20(28):1-143. - PMC - PubMed
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IRCT20160914029817N8 2018 {published data only}
    1. IRCT20160914029817N8. Investigating the effect of olive and bitter almonds on pressure ulcers. Iranian Registry of Clinical Trials 2018.
IRCT20190824044595N 2020 {published data only}
    1. IRCT20190824044595N. The effect of tele-nursing education on the incidence of pressure ulcer. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20190824044595N1 2020.
JPRN‐UMIN000002072 {published data only}
    1. JPRN-UMIN000002072. Effect of nutritional intervention to prevention and treatment of pressure ulcer. http://www.who.int/trialsearch/Trial2.aspx?TrialID=JPRN-UMIN000002072 2009.
JPRN UMIN000012216 {published data only}
    1. JPRN UMIN000012216. Treatment with supplementary L-ornithine in patients with pressure ulcers. UMIN Clinical Trials Registry: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R0000... 2013.
JPRN‐UMIN000022859 {published data only}
    1. JPRN-UMIN000022859. Evaluation of the correlation between serum carnitine and constipation. http://www.who.int/trialsearch/Trial2.aspx?TrialID=JPRN-UMIN000022859 2016.
Landes 2016 {published data only}
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Langkamp‐Henken 2000 {published data only}
    1. Langkamp-Henken B, Herrlinger-Garcia KA, Stechmiller JK, Nickerson-Troy JA, Lewis B, Moffatt L. Arginine supplementation is well tolerated but does not enhance mitogen-induced lymphocyte proliferation in elderly nursing home residents with pressure ulcers. Journal of Parenteral and Enteral Nutrition 2000;24(5):280-7. - PubMed
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Lu 2019 {published data only}
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Lupianez Perez 2013 {published data only}
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    1. Lupianez-Perez I, Morilla-Herrera JC, Kaknani-Uttumchanchandani S, Lupianez-Perez Y, Cuevas-Fernandez-Gallego M, Martin-Santos F, et al. A cost minimisation analysis of olive oil versus hyperoxygenated fatty acid treatment for the prevention of pressure ulcers in primary health care: a randomised controlled trial. Wound Repair and Regeneration 2017;25(5):846-51. [DOI: 10.1111/wrr.12586] - DOI - PubMed
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NCT00163007 {published data only}
    1. NCT00163007. Nutritional Therapy for Stroke Patients. https://clinicaltrials.gov/show/NCT00163007 2005.
NCT00502372 {published data only}
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NCT00507650 {published data only}
    1. NCT00507650. Increasing fluids in older adults to prevent & treat pressure ulcers. https://ClinicalTrials.gov/show/NCT00507650 2003.
NCT02711839 {published data only}
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NCT03658278 {published data only}
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References to studies awaiting assessment

Loreto Alvarez‐Nebreda 2021 {published data only}
    1. Loreto Alvarez-Nebreda M, Heng M, Javedan H, Franco-Garcia E, Rodriguez EK, Vlassakov KV, et al. Preoperative carbohydrate loading and clinical outcomes after trauma surgery in elderly patients: a randomized controlled study. European Geriatric Medicine 2021;12 Suppl 1:S244.
Ogawa 2021 {published data only}
    1. Ogawa K, Kurokawa Y, Kuwamura J, Watanabe M, Yamamoto T. Effect of enteral nutrition with eicosapentaenoic and gamma-linolenic acids for preventing pressure ulcers in patients after neurosurgery. Clinical Nutrition (Edinburgh, Scotland) 2016;35:S248.
    1. Ogawa K, Kuwamura J, Enomoto Y, Yamamaoto T. Clinical effects of enteral nutrition with eicosapentaenoic acids in the prevention of new pressure ulcer formation in critically Ill patients with cerebrovascular disease. A randomized, prospective, controlled study. 40th European Society for Clinical Nutrition. Clinical Nutrition 2018;37 Suppl 1:S291. [DOI: 10.1016/j.clnu.2018.06.2021] - DOI
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Pertikov 2019 {published data only}
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References to ongoing studies

CTRI/2019/07/020355 {published data only}
    1. CTRI/2019/07/020355. Impact of customized nutritional package on Macro and Micro Nutrients (MAMN) in wound healing. trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2019/07/020355 (first received 25 July 2019).
Hertig‐Godeschalk 2021 {published data only}
    1. Hertig-Godeschalk A, Brinkhof MW, ScheelSailer A, Perret C, Jenny A, Landmann G, et al. Vitamin D supplementation in chronic spinal cord injury (VitD-SCI): study protocol for a randomised controlled trial. BMJ Open 2021;11:e053951. [DOI: 10.1136/ bmjopen-2021-053951] - PMC - PubMed
Irct20181111041611N {published data only}
    1. IRCT20181111041611N4. Evaluation of the efficacy of high protein high calorie diet include L-Arginine, L-Glutamine and AY-Hydroxy AY-Methylbutyrate on pressure ulcers and anthropometric indices in 20-50 years adults in Kermanshah. trialsearch.who.int/Trial2.aspx?TrialID=IRCT20181111041611N4 (first received 09 July 2020).
JPRN‐UMIN000037811 {published data only}
    1. JPRN-UMIN000037811. Effects of nutritional intervention for high risk patients of pressure ulcer. trialsearch.who.int/Trial2.aspx?TrialID=JPRN-UMIN000037811 (first received 30 August 2019).
JPRN‐UMIN000045099 {published data only}
    1. JPRN-UMIN000045099. Effectiveness of an oral nutritional supplement (Lipimain400) for malnourished older patients in rural community - effectiveness of an oral nutritional supplement for malnourished older patients in rural community. trialsearch.who.int/Trial2.aspx?TrialID=JPRN-UMIN000045099 (first received 18 August 2021).
NCT03995407 {published data only}
    1. NCT03995407. 100% Whey Protein Based Diet In Enhancing Pressure Ulcer Healing. clinicaltrials.gov/study/NCT03995407?cond=%20Enhancing%20Pressure%20Ulce... (first received 20 June 2019).
NCT05308862 {published data only}
    1. NCT05308862. PROSENIOR. Prevention of Pressure Ulcers, Malnutrition, Poor Oral Health and Falls Among Older Persons Receiving Municipal Health Care and Are Registered in the Quality Registry Senior Alert. clinicaltrials.gov/study/NCT05308862?term=Quality%20Registry%20Senior%20... (first received 19 January 2022).
U1111‐1216‐6559 {published data only}
    1. U1111-1216-6559. Dressings, nutritional supplementation and teaching of the patient and caregiver for the healing of bedsores. ensaiosclinicos.gov.br/rg/RBR-7hfwzj (first received 19 July 2018).

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