Effect of Macronutrients or Micronutrients Supplementation on Nutritional Status, Physical Functional Capacity and Quality of Life in Patients with COPD: A Systematic Review and Meta-Analysis.

Given the importance that a correct and balanced nutrition has on patients with chronic obstructive pulmonary disease (COPD), supplementation of macro and micronutrients has been proposed, but the results of previous meta-analyses are contrasting. We performed an update of the latest evidence through a systematic review and meta-analysis of studies to assess the role of nutritional supplements in improving nutritional status, pulmonary function, physical performance, and quality of life of these patients.We included randomized controlled trials (RCTs) published between 01-01-2010 and 11-01-2023 evaluating the effectiveness of nutritional support in patients affected by stable COPD with an intervention of at least 2 weeks. Primary outcomes were changes in body mass index (BMI) and fat free mass index (FFMI). Secondary outcomes were exercise tolerance (6-min walking test, 6MWT), quality of life (St George's Respiratory Questionnaire, SGRQ) and respiratory function (FEV1). According with supplements type (macronutrients or micronutrients), we calculated the pooled adjusted mean difference (MD) and 95% confidence intervals (95%CIs) of the selected outcomes, using random-effects models in presence of high heterogeneity (I2>50%) or fixed-effects models otherwise. The risk of publication bias was evaluated with the trim and fill method.From 967 articles, 20 RCTs were included. Macronutrients supplementation improved BMI (MD 1.0 kg/m2, 95%CI 0.21-1.79), FFMI (MD 0.77 Kg/m2, 95%CI 0.48-1.06), 6MQT (MD 68.39 m, 95%CI 40.07-96.71), and SGRQ (MD -5.14, 95% CI -7.31-2.97), while it does not ameliorate respiratory function (MD 0.26% 95%CI -1.87-2.40). Micronutrients supplementation alone did not improve any of the considered outcomes.

Fortified whey beverage for improving muscle mass in chronic obstructive pulmonary disease: a single-blind, randomized clinical trial.

BACKGROUND: The development of effective nutritional supports for patients with chronic obstructive pulmonary diseases (COPD) is still challenging. This study was conducted to investigate the efficacy of daily consumption of fortified whey on inflammation, muscle mass, functionality, and quality of life in patients with moderate-to-severe COPD. METHODS: A single-blind, randomized trial study was performed on patients with COPD (n = 46). Participants in the intervention group (n = 23) daily received 250 ml of whey beverage fortified with magnesium and vitamin C for 8 weeks. Any changes in inflammatory cytokines (including interleukin- 6 (IL-6) and tumor necrosis factor (TNFα)) were the primary outcomes and the secondary outcomes were fat-free mass, handgrip strength, malnutrition, glutathione and malondialdehyde serum concentrations, and health-related quality of life (HRQoL). Body composition and muscle strength were measured by Bioelectrical Impedance Analysis (BIA) and hydraulic hand dynamometer, respectively. Fat-free mass index (FFMI) was also calculated. RESULTS: At the end of the study, 44 patients were analyzed. There were significant decreases in IL-6 concentrations in the intervention group compared to the control group. Also, FFMI, body protein, and handgrip strength increased significantly in the intervention group with significant changes between two groups. Moreover, improvement in health-related quality of life was observed in the intervention group compared to the control group. There were no significant changes in other study variables. CONCLUSIONS: This novel nutritional intervention decreased inflammatory cytokines levels, improved indices of skeletal muscle mass and muscle strength, and ultimately, increased HRQoL in patients with moderate-to-severe COPD. Thus, it is suggested to do further studies to assess the effects of nutrition intervention on COPD progression. TRIAL REGISTRATION: IR.SUMS.REC.1396.85 ( https://www.irct.ir/ ).

Role of Diet in Chronic Obstructive Pulmonary Disease Prevention and Treatment.

Chronic obstructive pulmonary disease is one of the leading causes of morbidity and mortality worldwide and a growing healthcare problem. Identification of modifiable risk factors for prevention and treatment of COPD is urgent, and the scientific community has begun to pay close attention to diet as an integral part of COPD management, from prevention to treatment. This review summarizes the evidence from observational and clinical studies regarding the impact of nutrients and dietary patterns on lung function and COPD development, progression, and outcomes, with highlights on potential mechanisms of action. Several dietary options can be considered in terms of COPD prevention and/or progression. Although definitive data are lacking, the available scientific evidence indicates that some foods and nutrients, especially those nutraceuticals endowed with antioxidant and anti-inflammatory properties and when consumed in combinations in the form of balanced dietary patterns, are associated with better pulmonary function, less lung function decline, and reduced risk of COPD. Knowledge of dietary influences on COPD may provide health professionals with an evidence-based lifestyle approach to better counsel patients toward improved pulmonary health.

Dietary intake of fatty acids and its relationship with FEV1/FVC in patients with chronic obstructive pulmonary disease.

BACKGROUND & AIMS: The deterioration of pulmonary function has been associated with increased levels of systemic inflammation that can be stimulated by consumption of saturated fatty acids and trans fats. We hypothesized that fatty acids intake impact on pulmonary function. However, evidence about the impact of different types of fatty acids on pulmonary function in patients with chronic obstructive pulmonary disease (COPD) is limited and heterogeneous. The aim of this study was to evaluate the association between intake of fatty acids and pulmonary function in patients with COPD. METHODS: Cross sectional study of patients diagnosed with COPD. The relationship between consumption of fatty acids and the FEV1/FVC ratio obtained by spirometry was assessed. Patients with exacerbations during the prior 2 months, diagnosis of asthma or administration of a dietary supplement were excluded. RESULTS: A simple linear regression showed that for each gram of carbohydrates and total l fatty acids intake, the FEV1/FVC ratio decreased -0.03 ml (ß: -0.03, 95% CI -0.06 to -0.01, p = 0.008) and -0.009 ml (ß: -0.00, 95% CI -0.02 to 0.00, p = 0.031) respectively. Pentadecanoic acid (C15:0) was associated with an increase of 0.47 ml in the FEV1/FVC ratio for each milligram intake (ß: 0.47, 95% CI 0.04 to 0.91, p = 0.031). Subsequently, when adjusted for calories intake, an increase of 0.53 ml was observed in the FEV1/FVC for each milligram of C15:0 fatty acid intake (ß:0.53, 95% CI 0.09 to 0.97, p = 0.018). CONCLUSION: A positive association was observed between pentadecanoic acid and the FEV1/FVC ratio with a beneficial effect on patients with COPD.

Dietary nitrate improved exercise capacity in COPD but not blood pressure or pulmonary function: a 2 week, double-blind randomised, placebo-controlled crossover trial.

Dietary nitrate may improve exercise tolerance in some healthy and clinical populations. Existing data regarding dietary nitrate in COPD is inconsistent. We conducted a 14d double-blind, randomised, placebo-controlled, crossover trial of daily nitrate-rich beetroot juice (BRJ; 12.9 mmol) versus nitrate-depleted BRJ (PL; 0.5 mmol). At baseline and after each condition, we assessed functional capacity (incremental shuttle walk test; ISWT), ambulatory blood pressure, pulmonary function, quality of life as well as exhaled nitric oxide (eNO), and plasma nitrate/nitrite (NOx). Eight subjects with COPD completed the trial. BRJ supplementation was associated with significantly increased NOx (p < .05) and a 14.6% increase in ISWT distance (+56 m, p = .00004) as well as a trend towards increased eNO compared to PL. There was no other differences. Dietary nitrate appears to have ergogenic effect in subjects with mild-moderate COPD. This effect does not appear to be related to altering blood pressure or pulmonary function.

The relationship between Vitamin D status and exacerbation in COPD patients- a literature review.

OBJECTIVE: To investigate the relationship between Vitamin D and exacerbation in COPD patients. METHODS: The PubMed database was searched for articles published from 2012 onwards using search terms related to Vitamin D and exacerbation in COPD patients. Meta-analysis, clinical trials, observational studies, and human studies were included. Non-English articles or articles with full text unavailable were excluded; a total of 15 articles were selected. RESULTS: The association between exacerbation frequency and Vitamin D levels in observational studies remains controversial, however, meta-analysis revealed a negative association between serum Vitamin D and exacerbation. Also, two clinical trials showed that Vitamin D3 supplementation in COPD patients reduced the risk of moderate and severe exacerbation. Vitamin D binding protein (VDBP) polymorphisms seem to affect patient exacerbation susceptibility. CONCLUSIONS: Few studies in literature have data related to diet, 25-hydroxyVitamin D [25(OH)D] and polymorphism in COPD exacerbation. One clinical trial indicates Vitamin D supplementation plays a role in COPD patients with hypovitaminosis D in preventing exacerbations. Further studies are needed to elucidate the role of Vitamin D in this population and to establish the best marker for Vitamin D, which patient subgroups will benefit, and the best supplement dosage without leading to toxicity.

Effect of Oligomeric Proanthocyanidin on the Antioxidant Status and Lung Function of Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND/AIM: Evidence exists that oxidative stress and oxidative damage play a pivotal role in chronic obstructive pulmonary disease (COPD). Oligomeric proanthocyanidins (OPCs) extracted from grape seeds have been shown to exhibit antioxidant capabilities greater than those of vitamin C and E. The objective of this study was to evaluate the effects of OPCs on antioxidant status and lung function in patients with COPD. PATIENTS AND METHODS: Patients were supplemented with 150 mg/day OPC (n=13) orally or with a placebo (n=14) for 8 weeks in a randomized double-blind clinical design. Changes in anthropometric values, lung function, oxidative state, and lipid profiles were assessed after OPC or placebo treatment for 8 weeks. RESULTS: The results showed that OPC supplementation significantly reduced the concentration of malondialdehyde, superoxide dismutase, and total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio. The concentration of HDL-C significantly increased in the OPC-treated group. The plasma triglyceride, TC and low-density lipoprotein cholesterol values and the activities of catalase and glutathione peroxidase also decreased, but did not significantly differ between the OPC- and placebo-treated groups. Lung function was not significantly different between the two groups after 8 weeks. CONCLUSION: OPC supplementation was effective in increasing the antioxidant capacity, in addition to improving the lipid profiles in patients with COPD.

Vitamin D supplementation in respiratory diseases: evidence from randomized controlled trials.

Pulmonary diseases are one of the most important causes of morbidity and mortality. Although vitamin D is best known for its role in calcium, phosphorus, and bone homeostasis, it has gained attention in the recent years because of a wide range of extraskeletal effects, including its immunomodulatory and antibacterial potential. Vitamin D deficiency is highly prevalent in chronic pulmonary diseases such as chronic obstructive pulmonary disease (COPD), cystic fibrosis, tuberculosis, and asthma, and several clinical studies have been conducted investigating the effect of vitamin D supplementation on disease outcomes. In this review, we searched for positive evidence on vitamin D supplementation from randomized controlled trials and elaborated on the optimal serum vitamin D levels and dosing regimens for an effective intervention. While vitamin D supplementation seems to be beneficial as an add­on treatment for adult patients with asthma and a potent intervention to reduce exacerbations in patients with COPD, there is little evidence for its therapeutic use in cystic fibrosis, pneumonia, and tuberculosis.

Estado nutricional y funcional en pacientes con enfermedad pulmonar obstructiva crónica: efectos de la suplementación nutricional oral (estudio OFOS) / Nutritional and functional state of patients with chronic obstructive pulmonary disease: effects of oral nutritional supplementation (OFOS study)

Introducción: la pérdida de peso y la desnutrición se asocian a un peor pronóstico de la enfermedad pulmonar obstructiva crónica (EPOC). Objetivo: el objetivo del estudio OFOS fue valorar la eficacia y tolerabilidad de una nueva fórmula nutricional oral en adultos con EPOC con pérdida de peso o desnutrición. Métodos: estudio prospectivo, unicéntrico, aleatorizado, abierto y controlado realizado en Lima (Perú). Se incluyeron 99 pacientes ambulatorios de ambos sexos (control [GC]: 49; suplemento [GS]: 50), entre 18 y 80 años con diagnóstico de EPOC y con pérdida involuntaria de peso en los últimos meses o desnutrición. Se evaluaron variables nutricionales, funcionales y de calidad de vida (CV) durante un periodo de intervención de tres meses. Resultados: a los tres meses, hubo un incremento del índice de masa corporal (IMC) y del índice de masa libre de grasa (IMLG) significativamente superior en el GS: IMC: 5,3% vs. 2,9%, p < 0,001; IMLG: 3,2% vs. 1,9%, p = 0,019. El GS mostró una reducción de casos con IMC < 21 kg/ m2 equivalente al 69% vs. 33% en el GC (p = 0,004). Las variables funcionales mostraron una tendencia a la mejoría favorable al GS, siendo significativa para la fuerza de la mano (hand-grip test) en el subgrupo de pacientes con IMLG bajo (p = 0,001). Todas las variables estudiadas de CV mejoraron significativamente en ambos grupos (p < 0,001). Conclusiones: la suplementación oral durante tres meses con una nueva fórmula completa, polimérica y normocalórica fue bien tolerada y eficaz para el soporte nutricional de pacientes diagnosticados de EPOC con pérdida de peso o desnutrición (AU)

Introduction: Weight loss and malnutrition are associated with a worse prognosis of chronic obstructive pulmonary disease (COPD). Objective: The main objective of the OFOS study was to assess the efficacy and tolerability of a new nutritional oral formula in adults with COPD with weight loss or malnutrition. Methods: Prospective, single-centre, randomized, open-label and controlled trial conducted in Lima (Peru). A total of 99 outpatients of both sexes were included (control [GC]: 49; supplement [GS]: 50), aged from 18 to 80 years old, who had been diagnosed with COPD and that suffered from malnutrition or involuntary weight loss during the last months. Nutritional, functional and quality of life (QoL) variables were evaluated during a three-month intervention. Results: At three months, there was an increase of body mass index (BMI) and fat free mass index (FFMI) significantly higher in the GS: IMC 5.3% vs 2.9%, p < 0.001; FFMI 3.2% vs 1.9%, p = 0.019. The GS showed a reduction of cases with BMI < 21 kg/m2 equivalent to 69% vs 33% in the GC (p = 0.004). Functional variables showed a favourable improvement trend in GS, being significant for the hand-grip test in the subgroup of patients with low FFMI (p = 0.001). All QoL studied variables significantly improved in both groups (p < 0.001. Conclusions: Oral supplementation with a complete, polymeric and normocaloric new nutritional formula for three months was well tolerated and effective for the nutritional support of patients diagnosed with COPD with weight loss or malnutrition (AU)

Dietary beetroot juice - effects on physical performance in COPD patients: a randomized controlled crossover trial.

BACKGROUND AND OBJECTIVE: Dietary beetroot juice (BR) supplementation has been shown to reduce the oxygen (O2) consumption of standardized exercise and reduce resting blood pressure (BP) in healthy individuals. However, the physiological response of BR in chronic obstructive pulmonary disease (COPD) remains controversial. The objective was to test exercise performance in COPD, supplementing with higher doses of BR for a longer duration compared to previous trials in this patient group. METHODS: Fifteen COPD patients consumed concentrated BR (2×70 mL twice daily, each containing 300 mg nitrate) or placebo (PL) (2×70 mL twice daily, nitrate-negligible) in a randomized order for 6 consecutive days. On day 7, participants consumed either BR or PL 150 min before testing. BP was measured before completing 6-minute walk test (6MWT) and two trials of submaximal cycling. The protocol was repeated after a minimum washout of 7 days. RESULTS: Plasma nitrite concentration was higher in the BR condition compared to PL (P<0.01). There was no difference between the BR and PL conditions regarding the covered distance during the 6MWT (mean ± standard error of the mean: 515±35 m (BR) vs 520±38 m (PL), P=0.46), O2 consumption of submaximal exercise (trial 1 P=0.31 vs trial 2 P=0.20), physical activity level (P>0.05), or systolic BP (P=0.80). However, diastolic BP (DBP) was reduced after BR ingestion compared to baseline (mean difference: 4.6, 95% CI: 0.1-9.1, P<0.05). CONCLUSION: Seven days of BR ingestion increased plasma nitrite concentrations and lowered DBP in COPD patients. However, BR did not increase functional walking capacity, O2 consumption during submaximal cycling, or physical activity level during the intervention period.

Undernutrition state in patients with chronic obstructive pulmonary disease. A critical appraisal on diagnostics and treatment.

'Undernutrition state' (UNS) is an ominous condition, in particular when associated with chronic obstructive pulmonary disease (COPD). In this review we discuss pathophysiological mechanisms and how UNS is defined and diagnosed. It seems unlikely that COPD-patients with established UNS have similar potential of reversibility (treatability) upon nutrition interventions as patients at a risk of developing such a condition, i.e. patients with low energy/nutrient intake, since pathophysiological, biochemical and metabolic conditions may differ substantially. We summarize the results of 7 of 17 published randomized controlled trials of nutritional supplementation in COPD-patients with defined UNS in the latest Cochrane review (2012). We thus excluded 10 of 17 trials included in review (2012), mostly because those studies also included patients with 'risk of' UNS. The seven included trials exhibit extensive heterogeneity for all studied variables. Most studies did not show beneficial effects of nutritional supplementation, although some reported minor increase in body weight and physical function of unclear clinical relevance. In contrast to the Cochrane review we conclude that it is difficult to draw firm conclusions regarding the effect of nutritional supplements in patients with COPD and UNS. Improved knowledge in this area is of utmost importance and some factors which should be considered in future studies are suggested.

A double blind randomized placebo control crossover trial on the effect of dietary nitrate supplementation on exercise tolerance in stable moderate chronic obstructive pulmonary disease.

BACKGROUND: Dietary nitrate supplementation has been shown to decrease the oxygen cost of exercise and prolong exercise tolerance, as measured by sub-maximal exercise endurance distance and time at 85% V̇O2max, in both elite athletes and normal healthy subjects. Patients with chronic obstructive pulmonary disease (COPD) have reduced quality of life and ability to perform activities of daily living attributable to diminished exercise tolerance, and dietary nitrate may be able to ameliorate this. METHODS: We performed a double-blind, computer-randomized placebo control crossover trial at a tertiary Australian hospital to investigate whether dietary nitrate supplementation as beetroot juice (BR) would augment submaximal exercise endurance in individuals with spirometrically confirmed stable moderate COPD. Volunteers underwent an incremental shuttle walk test to determine V̇O2max followed by a test dose of BR to establish safety in the study population. Participants performed an endurance shuttle walk test (ESWT) at 85% V̇O2max after randomization to either a 3 day wash-in of BR (4.8 mmol twice a day) or placebo (nitrate deplete BR), with a final dose on the morning of testing. They then crossed over after 4 day washout. Repeated measures two sided paired t-tests were employed. RESULTS: 35 participants were recruited with 19 completing the trial. In the initial safety phase, we measured systolic blood pressure over four hours post first dose of BR, and found a mean 10 mmHg decrement maximal at 1 hour. One individual developed symptomatic postural hypotension and was excluded. The primary outcomes of ESWT distance and time to fatigue improved by 11% and 6% respectively; however these differences did not achieve statistical significance (p = 0.494 and 0.693 respectively). CONCLUSIONS: Our study does not support a role for routine dietary nitrate supplementation for enhancement of exercise endurance in COPD. TRIAL REGISTRATION: Australia and New Zealand Clinical Trial Register: ACTRN12611001088932.

The effect of dietary nitrate supplementation on the oxygen cost of cycling, walking performance and resting blood pressure in individuals with chronic obstructive pulmonary disease: A double blind placebo controlled, randomised control trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) results in exercise intolerance. Dietary nitrate supplementation has been shown to lower blood pressure (BP), reduce the oxygen cost of exercise, and enhance exercise tolerance in healthy volunteers. This study assessed the effects of dietary nitrate on the oxygen cost of cycling, walking performance and BP in individuals with mild-moderate COPD. METHODS: Thirteen patients with mild-moderate COPD were recruited. Participants consumed 70 ml of either nitrate-rich (6.77 mmol nitrate; beetroot juice) or nitrate-depleted beetroot juice (0.002 mmol nitrate; placebo) twice a day for 2.5 days, with the final supplement ~3 hours before testing. BP was measured before completing two bouts of moderate-intensity cycling, where pulmonary gas exchange was measured throughout. The six-minute walk test (6 MWT) was completed 30 minutes subsequent to the second cycling bout. RESULTS: Plasma nitrate concentration was significantly elevated following beetroot juice vs. placebo (placebo; 48 ± 86 vs. beetroot juice; 215 ± 84 µM, P = 0.002). No significant differences were observed between placebo vs. beetroot juice for oxygen cost of exercise (933 ± 323 vs. 939 ± 302 ml: min(-1); P = 0.88), distance covered in the 6 MWT (456 ± 86 vs. 449 ± 79 m; P = 0.37), systolic BP (123 ± 14 vs. 123 ± 14 mmHg; P = 0.91), or diastolic BP (77 ± 9 vs. 79 ± 9 mmHg; P = 0.27). CONCLUSION: Despite a large rise in plasma nitrate concentration, two days of nitrate supplementation did not reduce the oxygen cost of moderate intensity cycling, increase distance covered in the 6 MWT, or lower BP.

The effect of protein supplementation on quality of life, physical function, and muscle strength in patients with chronic obstructive pulmonary disease.

BACKGROUND: The combination of protein supplementation with exercise is successful in increasing weight and energy intake, as well as exercise capacity and health-related quality of life in sarcopenic patients diagnosed with chronic obstructive disease (COPD). However, the potential benefit of protein supplementation for non-sarcopenic patients with COPD has yet not previously been examined. AIM: The aim of this trial was to evaluate the effect of protein supplementation on quality of life, physical function, muscle strength and biochemical blood markers in patients diagnosed with COPD undergoing nine weeks of pulmonary rehabilitation. DESIGN: A prospective, parallel group randomised clinical trial. SETTING: Patients referred from their general practitioners to the COPD rehabilitation outpatient programme at the local community rehabilitation centre. POPULATION: Patients (N.=53) with stable moderate to severe COPD diagnosed with COPD, 40 years or older and with a BMI<30. METHODS: The participants were assigned to one of two groups to receive either twice daily protein supplementation (9.3 g of protein/566.4 KJ) plus exercise or exercise only. Before and after nine weeks of rehabilitation, mental state was measured by means of St George Respiratory Questionnaire, physical performance was evaluated by shuttle walking test and maximal muscle strength test, and fasting blood samples were analyzed. RESULTS: Supplementing exercise with protein had no additional effect on any of the outcome measures. However, shuttle walk time, St George total score and subscore for impact improved as effect of time. CONCLUSION: This trial was unable to provide evidence for the effect of protein supplementation on quality of life, physical function, and muscle strength in non-sarcopenic patients with moderate to severe COPD. CLINICAL REHABILITATION IMPACT: The role of protein supplementation in COPD-rehabilitation should focus on identifying patients to receive supplement with protein and from those who will not benefit.

Vitamin D3 supplementation in patients with chronic obstructive pulmonary disease (ViDiCO): a multicentre, double-blind, randomised controlled trial.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often have vitamin D deficiency, which is associated with increased susceptibility to upper respiratory infection-a major precipitant of exacerbation. Multicentre trials of vitamin D supplementation for prevention of exacerbation and upper respiratory infection in patients with COPD are lacking. We therefore investigated whether vitamin D3 (colecalciferol) supplementation would reduce the incidence of moderate or severe COPD exacerbations and upper respiratory infections. METHODS: We did a randomised, double-blind, placebo-controlled trial of vitamin D3 supplementation in adults with COPD in 60 general practices and four Acute National Health Service Trust clinics in London, UK. Patients were allocated to receive six 2-monthly oral doses of 3 mg vitamin D3 or placebo over 1 year in a 1:1 ratio using computer-generated permuted block randomisation. Participants and study staff were masked to treatment assignment. Coprimary outcomes were time to first moderate or severe exacerbation and first upper respiratory infection. Analysis was by intention to treat. A prespecified subgroup analysis was done to assess whether effects of the intervention on the coprimary outcomes were modified by baseline vitamin D status. This trial is registered with ClinicalTrials.gov, number NCT00977873. FINDINGS: 240 patients were randomly allocated to the vitamin D3 group (n=122) and placebo group (n=118). Vitamin D3 compared with placebo did not affect time to first moderate or severe exacerbation (adjusted hazard ratio 0·86, 95% CI 0·60-1·24, p=0·42) or time to first upper respiratory infection (0·95, 0·69-1·31, p=0·75). Prespecified subgroup analysis showed that vitamin D3 was protective against moderate or severe exacerbation in participants with baseline serum 25-hydroxyvitamin D concentrations of less than 50 nmol/L (0·57, 0·35-0·92, p=0·021), but not in those with baseline 25-hydroxyvitamin D levels of at least 50 nmol/L (1·45, 0·81-2·62, p=0·21; p=0·021 for interaction between allocation and baseline serum 25-hydroxyvitamin D status). Baseline vitamin D status did not modify the effect of the intervention on risk of upper respiratory infection (pinteraction=0·41). INTERPRETATION: Vitamin D3 supplementation protected against moderate or severe exacerbation, but not upper respiratory infection, in patients with COPD with baseline 25-hydroxyvitamin D levels of less than 50 nmol/L. Our findings suggest that correction of vitamin D deficiency in patients with COPD reduces the risk of moderate or severe exacerbation. FUNDING: UK National Institute for Health Research.

Dietary nitrate supplementation improves exercise performance and decreases blood pressure in COPD patients.

Dietary nitrate (NO3(-)) supplementation via beetroot juice has been shown to increase the exercise capacity of younger and older adults. The purpose of this study was to investigate the effects of acute NO3(-) ingestion on the submaximal constant work rate exercise capacity of COPD patients. Fifteen patients were assigned in a randomized, single-blind, crossover design to receive one of two treatments (beetroot juice then placebo or placebo then beetroot juice). Submaximal constant work rate exercise time at 75% of the patient's maximal work capacity was the primary outcome. Secondary outcomes included plasma NO3(-) and nitrite (NO2(-)) levels, blood pressure, heart rate, oxygen consumption (VO2), dynamic hyperinflation, dyspnea and leg discomfort. Relative to placebo, beetroot ingestion increased plasma NO3(-) by 938% and NO2(-) by 379%. Median (+interquartile range) exercise time was significantly longer (p = 0.031) following the ingestion of beetroot versus placebo (375.0 + 257.0 vs. 346.2 + 148.0 s, respectively). Compared with placebo, beetroot ingestion significantly reduced iso-time (p = 0.001) and end exercise (p = 0.008) diastolic blood pressures by 6.4 and 5.6 mmHg, respectively. Resting systolic blood pressure was significantly reduced (p = 0.019) by 8.2 mmHg for the beetroot versus the placebo trial. No other variables were significantly different between the beetroot and placebo trials. These results indicate that acute dietary NO3(-) supplementation can elevate plasma NO3(-) and NO2(-) concentrations, improve exercise performance, and reduce blood pressure in COPD patients.