Effects of Nutritional Interventions in Individuals with Chronic Obstructive Lung Disease: A Systematic Review of Randomized Controlled Trials

Figures & data

Table 1 Inclusion and Exclusion Criteria

Inclusion Criteria:

• Population: Individuals diagnosed with COPD  • Exposure: Orally administered non-micronutrients based nutritional interventions  • Comparators: Not receiving similar nutritional interventions  • Outcome: Changes in pulmonary function, physical function, health-related quality of life, and inflammatory markers  • Study design: Randomized controlled trials  • Language: English, German, French, Russian, Norwegian, Swedish, Danish and Estonian  • Publication status: Published articles indexed in Medline, Embase & Cochrane

Exclusion Criteria:

• Animal studies/cell studies  • Parenteral nutrition  • Patients admitted due to COPD exacerbation  • Hospital (inpatient) setting  • General dietary counseling without specific intervention  • Intervention duration of ≤ 7 days  • Exclusively presenting data for malnourished or obese subjects (BMI ≤ 18.5 or ≥ 30 kg/m2)

Figure 1 PRISMA flow diagram.

Notes: PRISMA figure adapted from Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta- Analyses: The PRISMA Statement. PLoS Med 6(7):e1000097. Creative Commons.¹⁷ For more information, visit www.prisma-statement.org.

Table 2 Design, Population, Intervention, and Results of Included Studies

Author (Year)	Design	Quality	Population*	Nutritional Intervention (Control Group)	Results
				Duration
Ahnfeldt-Mollerup et al^Citation19	Prospective, parallel group randomized clinical trial	Poor	53 participants with stable moderate to severe COPD	2x/day protein bar containing 9.3 g protein each (no placebo)	No significant differences between groups in assessments of physical function (SWT, MMST), health-related quality of life impairment (SGRQ) or inflammation markers (CRP, leukocytes).
				9 weeks
Al-Azzawi et al^Citation25	Prospective randomized controlled double-blinded clinical trial.	Poor	100 participants with mild to moderate COPD	2x/day capsule containing 1 g cold-pressed black seed oil (no placebo)	Greater improvements for intervention group in all outcomes assessing lung function (FEV1, FVC, FEV1/FVC, PEF, FEF25-75) and inflammation (TNF-α, IL-6) compared to control.
				12 weeks
Baldrick et al^Citation23	Open-label randomized controlled trial	Fair	81 participants with stable moderate to severe COPD	≥5 portions/day of fruits and vegetables (≤2 portion/day)	No significant changes in outcome measures assessing lung function (FEV1, FVC, FEV1/FVC) or inflammation (sputum IL-8, sputum myeloperoxidase, plasma CRP) for either group.
				12 weeks
Behnia et al^Citation21	Randomized, parallel, placebo-controlled, single-blind trial	Poor	25 participants with stable mild to severe COPD	1x/day 80 mL beetroot juice (placebo blackcurrant juice)	No significant differences between groups in measures assessing lung function (FEV1, FVC, FEV1/FVC, FEF25-75, FEF25), health-related quality of life impairment (SGRQ) or dyspnea (Borg RPE during submaximal and maximal exercise).
				8 days
Constantin et al^Citation29	Randomized, parallel, placebo-controlled, double-blind trial	Fair	59 patients with stable severe to very severe COPD	3x/week nutritional drink containing 19 g protein and 49 g carbohydrate after exercise session (non-caloric placebo drink)	No significant difference between groups in outcomes assessing physical function (isometric quadriceps strength and isokinetic work).
				8 weeks
Keranis et al^Citation24	Randomized, controlled single-blinded trial	Fair	120 participants with stable COPD	2x/year information on the benefits of an antioxidant-rich diet with increased fruit and vegetable consumption (no placebo)	Greater annual improvement in outcome assessing lung function (FEV1) for intervention group compared to control.
				3 years
Kerley et al^Citation20	Randomized, crossover, placebo-controlled, double-blind trial	Good	10 participants with stable COPD	1x/day 140 mL beetroot juice (nitrate depleted beetroot juice)	No significant differences between groups in lung function (FEV1, FVC). Significant improvement in physical function (ISWT) for intervention group compared to control. No significant difference between groups in health-related quality of life (CCQ).
				14 days
Knowles et al^Citation30	Randomized single-blinded crossover trial	Good	25 participants with stable severe COPD	Powdered supplement containing 24% protein, 22% fat and 54% carbohydrates in order to increase daily caloric intake by 50% (no placebo)	No significant differences between groups in outcomes assessing lung function (FEV1, FVC) or systemic inflammation (lymphocyte count).
				8 weeks
Muhamad et al^Citation26	Single-blinded randomized controlled trial	Fair	60 participants with COPD	1x/day packet of 20 mg Tualang honey (no placebo)	No significant differences between groups in lung function (FEV1, FVC, FEV1/FVC, FEF25-75). Significant improvement of health-related quality of life impairment (SGRQ) for intervention group compared to control.
				6 months
Panahi et al^Citation27	Randomized open-label clinical trial	Poor	97 participants with stable mild to moderate COPD or asthma	1x/day 9 tablets containing 300 mg Chlorella vulgaris extract (no placebo)	No significant differences between groups in lung function (FEV1, FVC, FEV1/FVC, FEF25-75) and health-related quality of life (SGRQ symptom subscale). Greater improvement for SGRQ item in sputum production for intervention group compared to control.
				8 weeks
Pavitt et al^Citation22	Randomized, placebo controlled, double blinded trial	Good	165 participants with stable moderate to severe COPD	2x/week 140 mL beetroot juice before supervised pulmonary rehabilitation session (nitrate depleted placebo juice)	Greater improvement in outcomes assessing physical function (ISWT, daily steps and time spent in activity > 3 METs) for intervention group compared to control, but not on the level of physical activity. No significant difference between groups in health-related quality of life (CAT) or dyspnea (MRC).
				8 weeks
Steiner et al^Citation31	Randomized placebo-controlled clinical trial	Fair	85 participants with stable COPD	3x/day nutritional drink containing 190 kcal, 60% carbohydrates, 20% fat, 20% protein (non-nutritive placebo)	No significant differences between groups in physical function (ISWT, ESWT, hand grip strength, quadriceps strength). For participants with BMI > 19 there was a significant improvement in the ISWT for the intervention group compared to control.
				7 weeks
Sugawara et al^Citation28	Randomized, parallel, controlled, non-blinded trial	Fair	36 patients with stable COPD	2x/day nutritional drink containing 200 kcal, 20% protein, 25% lipids, 53% sugars, 1.8% fiber + added Whey peptide, n-3-fatty acids and vitamin A, C and D (no placebo)	Greater improvement for intervention group in physical function outcomes (WBI, 6MWT), health-related quality of life (CRQ total and emotional subscale) and systemic inflammation (IL6, IL-8, hsCRP, TNF-α) compared to control. No significant difference between groups in dyspnea (CRQ dyspnea subscale, MRC).
				12 weeks

Note: *All participants were adults with COPD, mostly aged 40 years and above.

Abbreviations: 6MWT, six-minute walking test; Borg RPE, Borg rating of perceived exertion; CCQ, clinical COPD questionnaire; COPD, chronic obstructive pulmonary disease; CAT, COPD assessment test; CRP, C-reactive protein; CRQ-SR, chronic respiratory disease questionnaire – self-reported; ESWT, endurance shuttle walk test; FEF, forced expiratory flow; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; hsCRP, high sensitivity CRP; IL-6, interleukin 6; IL-8, interleukin 8; ISWT, incremental shuttle walk test; MET, metabolic equivalent of task; MMST, maximal muscle strength test; MRC, medical research council; PEF, peak expiratory flow; PR, pulmonary rehabilitation; SGRQ, St. George's respiratory questionnaire; SWT, shuttle walk test; TNF-α, tumor necrosis factor-alpha; WBI, weight bearing index.

Moher DSL, Clarke M, Ghersi D, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015;4(1):1. doi:10.1186/2046-4053-4-1

 PubMed Web of Science ®Google Scholar

Ahnfeldt-Mollerup P, Hey H, Johansen C, Kristensen S, Brix Lindskov J, Jensahnfeldt-Mollerupen C. The effect of protein supplementation on quality of life, physical function, and muscle strength in patients with chronic obstructive pulmonary disease. Eur J Phys Rehabil Med. 2015;51(4):447–456.

 PubMed Web of Science ®Google Scholar

Al-Azzawi MA, AboZaid MMN, Ibrahem RAL, Sakr MA. Therapeutic effects of black seed oil supplementation on chronic obstructive pulmonary disease patients: a randomized controlled double blind clinical trial. Heliyon. 2020;6(8):e04711. doi:10.1016/j.heliyon.2020.e04711

 PubMed Web of Science ®Google Scholar

Baldrick FR, Elborn JS, Woodside JV, et al. Effect of fruit and vegetable intake on oxidative stress and inflammation in COPD: a randomised controlled trial. Eur Respir J. 2012;39(6):1377–1384. doi:10.1183/09031936.00086011

 PubMed Web of Science ®Google Scholar

Behnia M, Wheatley CM, Avolio A, Johnson BD. Influence of dietary nitrate supplementation on lung function and exercise gas exchange in COPD patients. Nitric Oxide. 2018;76:53–61. doi:10.1016/j.niox.2018.03.009

 PubMed Web of Science ®Google Scholar

Constantin D, Menon MK, Houchen-Wolloff L, et al. Skeletal muscle molecular responses to resistance training and dietary supplementation in COPD. Thorax. 2013;68(7):625–633. doi:10.1136/thoraxjnl-2012-202764

 PubMed Web of Science ®Google Scholar

Keranis E, Makris D, Rodopoulou P, et al. Impact of dietary shift to higher-antioxidant foods in COPD: a randomised trial. Eur Respir J. 2010;36(4):774–780. doi:10.1183/09031936.00113809

 PubMed Web of Science ®Google Scholar

Kerley CP, James PE, McGowan A, Faul J, Cormican L. Dietary nitrate improved exercise capacity in COPD but not blood pressure or pulmonary function: a 2 week, double-blind randomised, placebo-controlled crossover trial. Int J Food Sci Nutr. 2019;70(2):222–231. doi:10.1080/09637486.2018.1492521

 PubMed Web of Science ®Google Scholar

Knowles JB, Fairbarn MS, Wiggs BJ, Chan-Yan C, Pardy RL. Dietary supplementation and respiratory muscle performance in patients with COPD. Chest. 1988;93(5):977–983. doi:10.1378/chest.93.5.977

 PubMed Web of Science ®Google Scholar

Muhamad R, Draman N, Aziz AA, Abdullah S, Jaeb MZM. The effect of Tualang honey on the quality of life of patients with chronic obstructive pulmonary disease: a randomized controlled trial. J Taibah Univ Med Sci. 2018;13(1):42–50. doi:10.1016/j.jtumed.2017.05.014

 PubMed Web of Science ®Google Scholar

Panahi Y, Tavana S, Sahebkar A, Masoudi H, Madanchi N. Impact of adjunctive therapy with chlorellav ulgaris extract on antioxidant status, pulmonary function, and clinical symptoms of patients with obstructive pulmonary diseases. Sci. 2012;80(3):719–730.

 Google Scholar

Pavitt MJ, Tanner RJ, Lewis A, et al. Oral nitrate supplementation to enhance pulmonary rehabilitation in COPD: ON-EPIC a multicentre, double-blind, placebo-controlled, randomised parallel group study. Thorax. 2020;75(7):547–555. doi:10.1136/thoraxjnl-2019-214278

 PubMed Web of Science ®Google Scholar

Steiner MC, Barton RL, Singh SJ, Morgan MD. Nutritional enhancement of exercise performance in chronic obstructive pulmonary disease: a randomised controlled trial. Thorax. 2003;58(9):745–751. doi:10.1136/thorax.58.9.745

 PubMed Web of Science ®Google Scholar

Sugawara K, Takahashi H, Kashiwagura T, et al. Effect of anti-inflammatory supplementation with whey peptide and exercise therapy in patients with COPD. Respir Med. 2012;106(11):1526–1534. doi:10.1016/j.rmed.2012.07.001

 PubMed Web of Science ®Google Scholar