Fish Oil and HMB Supplementation in COPD
Condition: Chronic Obstructive Pulmonary Disease
MeSH terms: Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Study type: Interventional

Summary: 
      In the present study, the role of chronic (10 weeks) intake of low dose (2g/day) of EPA+DHA
      in whole body protein metabolism, and functional performance and systemic inflammation will
      be examined, and whether adding either HMB at 3.0 g/d to the low dose of EPA+DHA (2.0 g/d)
      will enhance these effects even more.
    

Detailed description: 
      Weight loss commonly occurs in patients with Chronic Obstructive Pulmonary Disease (COPD),
      negatively influencing their quality of life, treatment response and survival. Furthermore,
      limb muscle dysfunction (weakness and/or enhanced fatigue) is a major systemic comorbidity in
      patients with Chronic Obstructive Pulmonary Disease (COPD), negatively affecting their
      exercise performance, physical activity, quality of life, and mortality. As nutritional
      abnormalities are main contributors to muscle loss and dysfunction in COPD, nutritional
      support is viewed as an essential component of integrated care in these patients.

      Although nutritional support is effective in the treatment of weight loss in COPD, attempts
      to increase muscle mass and function in COPD by supplying large amounts of protein or
      calories to these patients have been small. This suggests that gains in muscle mass and
      function are difficult to achieve in COPD unless specific metabolic abnormalities are
      targeted. The investigators and other researchers found that low muscle mass in COPD was
      strongly associated with elevated whole body protein turnover and increased myofibrillar
      protein breakdown rates indicative of muscle contractile protein loss. The investigators have
      extended this finding recently to normal weight COPD patients characterized by muscle
      weakness using a more precise and accurate pulse method of tau-methylhistidine tracer.

      A substantial number of COPD patients, underweight as well as normal weight to obese, are
      characterized by an increased inflammatory response as evidenced by elevated levels of the
      pro-inflammatory cytokines (Tumor Necrosis Factor (TNF)-α, Interleukin (IL) 6 and 8, and the
      soluble TNF-α receptors (55 and 75). Furthermore, CRP levels are elevated in COPD and
      associated with reduced quadriceps strength, lower maximal and submaximal exercise capacity
      and increased morbidity.

      One of the few agents capable to suppress the generation of pro-inflammatory cytokines are
      eicosapentanoic acid (EPA) and docosahexanoic acid (DHA), primary ω-3 fatty acids found in
      fish oils.

      Previous experimental research and clinical studies in cachectic conditions (mostly
      malignancy) indicate that polyunsaturated fatty acids (PUFA) are able to attenuate protein
      degradation by improving the anabolic response to feeding and by decreasing the acute phase
      response. Eicosapentaenoic acid (EPA), in combination with docosahexaenoic acid (DHA), has
      been shown to effectively inhibit weight loss in several disease states, however weight
      weight and muscle mass and function increase was not present or minimal. Also in healthy
      older adults, fish oil can slow the decline in muscle mass and function. A randomized
      clinical trial in COPD patients showed that extra nutritional supplementation with PUFAs
      daily of 1000 mg EPA+DHA as adjunct to exercise training during 8 weeks enhanced exercise
      capacity but did not lead to muscle mass gain. The patients who did not respond adequately (<
      2% gain in weight), had a higher TNF-α level than those who did gain sufficient weight, which
      is in line with previous data in COPD showing an association between an increased systemic
      inflammation with non-response to nutritional therapy.

      Although previous studies support the concept of EPA+DHA supplementation to ameliorate the
      systemic inflammatory response and decrease protein breakdown, there is no information
      present on the effects of EPA+DHA supplementation on whole body and muscle protein metabolism
      in COPD. The investigators have recently examined the dose-response effects of 0, 2 and 3.5 g
      of EPA+DHA intervention ( EPA / DHA) for 4 weeks in stable moderate to severe COPD patients
      (8pts /group) (unpublished data) but were not able to find a positive effect of muscle mass
      and strength, even with the highest dose, likely related to the relatively short (4 week)
      supplementation period. The effect of EPA+DHA intervention on whole body and muscle protein
      synthesis and breakdown rates is currently being analysed.

      Although numerous animal studies have shown the benefit of HMB in downregulating muscle
      protein breakdown under catabolic conditions, there is very little data in COPD patients.
      Others have tested HMB (3g/d) in COPD patients in the ICU and reported anti-inflammatory
      benefits and improvement in pulmonary function. In patients with bronchiectasis, 24 week
      supplementation with an ONS containing HMB (1.5g/d) versus standard of care during pulmonary
      rehabilitation program, resulted in benefits on body composition, muscle strength and QoL. A
      combination of HMB and EPA/DHA in a mouse model of cancer cachexia showed a synergy between
      the two ingredients on preventing muscle loss and downregulation of muscle protein
      degradation.
    

Intervention name(s): Capsule + Powder supplementation; stable tracer infusion
Intervention type(s): Dietary Supplement; Other
Intervention description(s): For Fish oil and Placebo oil, treatment will be provided in capsules.Each group will receive dose distributed to 3 capsules per day. Participants will be instructed to take all capsules with morning meal. . For HMB and a placebo powder, product will be delivered as powder taken with water or non-carbonated beverage (like juice). Product will be provided in 2 sachets/day. One sachet should be consumed with breakfast and the other prior to bedtime (approx. 10pm).; labeled amino acids L-Phenylalanine (ring-13C6), L-Tyrosine (ring-D4), and tau-Methylhistidine will be infused as a single injection. Subsequently, the catheter will be used for arterialized venous blood samples (3 ml) drawn multiple through the day
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Supportive Care
Keywords: Fish Oil supplement; HMB supplement