Summary
The symptoms of chronic obstructive pulmonary disease severely impact the ability to breathe and negatively affect quality of life. Loss of weight, muscle mass and function are commonly present in patients with chronic obstructive pulmonary disease, which contributes to progressive disability and enhance mortality risk. Clinical trials have shown that omega-3 fatty acids such as DHA are beneficial against these comorbidities and may thus be considered to be included in treatment plans.
 
Introduction
Chronic obstructive pulmonary disease (COPD) is defined as chronic obstruction of airflow as a result of airway abnormalities. This leads to respiratory symptoms such as shortness of breath, coughing (dry and wet). Despite (limited) pharmacological treatment options, a large number of COPD patients continue to experience symptoms that can often flare up and lead to hospitalizations, severely impacting quality of life. Common comorbidities of COPD are impairments in protein metabolism, sarcopenia (the loss of muscle mass and function as a result of disease) and cachexia (illness-related involuntary weight loss). When the balance between protein synthesis and protein breakdown shifts in favour of the latter, sarcopenia arises. Both sarcopenia and cachexia increase the COPD disease burden and mortality risk, warranting inclusion of therapies targeting these comorbidities in COPD treatment plans. Modern COPD treatment is focused on pulmonary rehabilitation, which encompasses pharmacological therapies, exercise training and diet. Studies have implicated a positive role of omega-3 fatty acids in the context of COPD disease burden, supported by recent clinical trials with omega-3 containing supplementation for COPD patients.
 
Research findings
Suspected beneficial effects of DHA and EPA in combination with vitamin D against cachexia in COPD patients were investigated by Calder and collaborators (Calder et al., 2018). For a period of 12 weeks, 45 patients with moderate to severe COPD and cachexia or an underweight body mass index score received either a daily placebo or targeted medical nutrition solution. Twenty-two patients received the targeted medical nutrition consisting of 10g whey protein, a minimum of 2g DHA+EPA and 10 µg vitamin D. The remaining 23 patients received the placebo consisting of sunflower oil and milk protein. The set outcome measurements were muscle function, exercise tolerance and COPD progression. At the end of the supplementation period, no treatment effect was discovered for muscle function. Yet, it was found that the supplementation group were less affected by the classic COPD symptoms of shortness of breath and fatigue after exercise compared to the placebo group. Furthermore, 50% of the patients in the placebo group experienced COPD progression, compared to 40% of the patients in the supplementation group.

Van de Bool and colleagues set out to test the efficacy of nutritional supplementation (containing DHA+EPA) in COPD comorbidity health indicators during targeted exercise pulmonary rehabilitation (van de Bool et al., 2017). For a period of 4 months, 81 COPD patients (men and women) aged 43-80 with low muscle mass were divided in a placebo group and supplementation group during their pulmonary rehabilitation. They drank 2-3 units of omega-3 containing supplementation (42 individuals) or a caloric equivalent placebo (39 individuals) per day. Each unit contained 248.8mg EPA and 118.5mg DHA, which equates to a total of 497.6-764.4mg EPA and 237-355.5mg DHA per day in the supplementation group. After 4 months, the supplementation group showed an increase in blood plasma EPA+DHA levels, compared to a decrease of DHA levels in the placebo group. As expected, both groups showed a targeted exercise-induced increase in skeletal muscle mass after the trial. Yet, the supplementation group showed additional improvements in the context of sarcopenia and cachexia: these patients had an increase in body mass and fat mass compared to the baseline and placebo after 4 months. Additionally, the supplementation group showed greater improvements in muscle strength of respiratory muscles compared to the placebo group. On basis of these results, the authors concluded that supplementation containing vitamin D, omega-3 fatty acids and leucine improves outcomes of targeted exercise during pulmonary rehabilitation in COPD patients.

In their 2022 study, Engelen and colleagues set out to investigate the effects of daily EPA+DHA supplementation on protein homeostasis and muscle health in COPD patients (Engelen et al., 2022). Thirty-two moderate to severe COPD patients were divided into three daily supplementation groups for a period of 4 weeks: 3.5g daily DHA+EPA (10 individuals), 2g daily DHA+EPA (10 individuals) or daily olive oil as placebo (12 individuals). After 4 weeks, the authors discovered that the high and low dose DHA+EPA groups had lower protein breakdown rates during overnight-fasted condition compared to the placebo group. Additionally, the high dose DHA+EPA group had a higher protein synthesis rate following a meal compared to the placebo group. This group also showed a higher total body lean mass compared to the placebo group. These findings indicate that supplementation with DHA and EPA for COPD patients improves protein homeostasis and may protect against sarcopenia.
 
Conclusion
The studies mentioned above have provided valuable insight into the beneficial role of omega-3 fatty acids such as DHA in the context of COPD. Namely, supplementation with omega-3 fatty acids is beneficial against the COPD comorbidities impaired protein homeostasis, sarcopenia and cachexia, either on its own or in combination with targeted exercise. It should be noted that these studies did not investigate the effects of omega-3 containing supplementation on the disease mechanism itself.  Yet, this does not take away the proven beneficial effects of omega-3 fatty acid supplementation in the disease burden and quality of life of COPD patients.
 
References
Calder, P. C., Laviano, A., Lonnqvist, F., Muscaritoli, M., Öhlander, M., & Schols, A. (2018). Targeted medical nutrition for cachexia in chronic obstructive pulmonary disease: A randomized, controlled trial. Journal of Cachexia, Sarcopenia and Muscle, 9(1), 28–40. https://doi.org/10.1002/jcsm.12228

Engelen, M. P., Jonker, R., Sulaiman, H., Fisk, H. L., Calder, P. C., & Deutz, N. E. (2022). ω-3 polyunsaturated fatty acid supplementation improves postabsorptive and prandial protein metabolism in patients with chronic obstructive pulmonary disease: A randomized clinical trial. The American Journal of Clinical Nutrition, 116(3), 686–698. https://doi.org/10.1093/ajcn/nqac138

van de Bool, C., Rutten, E. P. A., van Helvoort, A., Franssen, F. M. E., Wouters, E. F. M., & Schols, A. M. W. J. (2017). A randomized clinical trial investigating the efficacy of targeted nutrition as adjunct to exercise training in COPD. Journal of Cachexia, Sarcopenia and Muscle, 8(5), 748–758. https://doi.org/10.1002/jcsm.12219