Targeted Nutritional Strategies
The mechanism by which vitamin D affects the pathogenesis of COPD is unclear. However, studies show that vitamin D can modulate the activity of various immune cells (Herr 2011), inhibit inflammatory responses (Hopkinson 2008), and regulate airway smooth muscles (Banerjee 2012).
A review of molecular and animal experiments showed that vitamin D regulates airway contraction, inflammation, and remodeling in airway smooth muscles characteristic of COPD (Banerjee 2012). A cross-sectional study found that higher plasma levels of vitamin D are associated with increased bone mineral density and exercise capacity in people with COPD (Romme 2012). Evidence also showed that high dose vitamin D supplementation improved respiratory muscle strength and exercise capacity in people with COPD (Hornikx 2011).
A study among 414 smokers with COPD showed that vitamin D deficiency is highly prevalent in this population, and correlates with disease severity. The study also found that genetic determinants for low vitamin D levels were associated with an increased risk of COPD (Janssens 2010).
Other COPD intervention studies are underway to examine the effect(s) of 3,000 – 6,000 IU of vitamin D3 on rehabilitation (NCT01416701), as well as time to first upper respiratory infection and first moderate-to-severe exacerbation (NCT00977873) (clinicaltrials.gov 2012).
Antioxidants: Vitamins A, C, and E
Vitamin A plays a role in proper lung development (in the embryonic stage) and repair of damaged lung tissue. Animal models showed that mice with low vitamin A levels were more likely to develop emphysema after 3 months of exposure to cigarette smoke compared to mice with normal vitamin A levels (Van Eijl 2011). In one study, high dietary vitamin A intake (greater than 2,770 IU daily) was associated with a 52% reduction in risk of COPD (Hirayama 2009).
Vitamin E levels are low in smokers, increasing their susceptibility to free radical damage (Bruno 2005). A 10-year, randomized, population-based trial of 38,597 healthy women reported that supplementing with 600 IU of vitamin E reduced the risk of chronic lung disease by 10% (Agler 2011).
A review of population studies reported that low levels of vitamins E and C were associated with more wheezing, phlegm, and dyspnea. Levels of vitamins E and A were significantly lower during acute exacerbations of COPD compared to stable COPD (Tsiligianni 2010). A case-control study showed that people with COPD had significantly lower serum levels of vitamins A, C, E, and carotenoids compared to healthy controls. The COPD group also had higher white blood cell DNA damage and consumed fewer vegetables and fruits than the healthy group (Lin 2010).
N-acetylcysteine (NAC), a glutathione precursor, can dissolve mucus (mucolytic properties) and repair damage caused by reactive oxygen species (Sadowska 2007; Sadowska 2012).
A comprehensive review of studies reported that oral NAC lowered the risk of exacerbations and improved symptoms in patients with chronic bronchitis compared to placebo (Stey 2000). NAC (600 mg) given twice daily for two months reduced the oxidant burden in the airways of people with stable COPD (De Benedetto 2005). Experimental and clinical studies also showed that NAC can reduce symptoms, exacerbations, and slow declining lung function in COPD (Dekhuijzen 2006).
Treating moderate-to-severe COPD with 1,200 mg of oral NAC daily for 6 weeks improved performance on lung function tests after exercise. NAC treatment also reduced air trapping in the lungs compared to placebo (Stav 2009). Clinical evidence indicates that administering 1,200 to 1,800 mg of NAC daily counteracts oxidative stress among subjects with COPD (Foschino 2005; De Benedetto 2005). In contrast, a large multi-center COPD trial reported no difference between NAC and placebo in the decline of lung function. However, those taking NAC who were not on corticosteroids appeared to have fewer exacerbations (Decramer 2005).
A clinical trial is underway to investigate the effect of adding 1,200 mg of NAC daily to standard treatment to reduce air trapping and exacerbations in stable COPD (NCT01136239).
Ginseng has traditionally been used in Chinese medicine to treat a wide range of respiratory symptoms (An 2011). A review of twelve small randomized studies showed that ginseng may be a potential adjunct therapy in patients with COPD. Oral ginseng formula combined with pharmacotherapy improved respiratory symptoms and quality of life, and reduced exacerbation of COPD compared to placebo, non-ginseng formula, or pharmacotherapy alone (An 2011). These results confirmed a previous study on the effects of 200 mg of ginseng extract daily on pulmonary function tests (Gross 2002). Pulmonary function and exercise capacity were significantly improved among people with moderate-to-severe COPD taking ginseng extract compared to placebo. A 2011 article reported that there is a large, multi-center, randomized, controlled study underway to evaluate the safety and efficacy of 200 mg of standardized root extract of Panax ginseng daily for 24 weeks among people with moderate COPD (Xue 2011).
Emerging evidence shows that sulforaphane, a compound in broccoli and other cruciferous vegetables, can potentially augment the anti-inflammatory effects of corticosteroids in COPD (Malhotra 2011). A study showed that histone deacetylase 2 (HDAC2), an enzyme that enables corticosteroids to reduce inflammation, was low in the lung tissue of people with COPD (Cosio 2004; Barnes 2006). Evidence revealed that sulforaphane can restore corticosteroid sensitivity and increase the activity of HDAC2 (Malhotra 2011). Sulforaphane can also counteract oxidative stress by activating Nrf2, a chemical pathway involved in protecting cells from oxidative stress caused by cigarette smoke and other irritants (Harvey 2011; Malhotra 2011; Starrett 2011).
Coenzyme Q10 (CoQ10) is a powerful antioxidant (Quinzii 2010). Indirect evidence shows potential benefit of supplementation in people with COPD who have low CoQ10 levels (Tanrikulu 2011).
A case-control study showed that CoQ10 levels were lower and oxidative stress markers increased during exacerbation of COPD, indicating an imbalance in antioxidant defense during those periods. The authors suggest supplementation with CoQ10 may reduce COPD exacerbation (Tanrikulu 2011).
A study of the effects of CoQ10 on the exercise performance of athletes and non-athletes showed that plasma levels of CoQ10 increased after 2 weeks of supplementation. Participants who supplemented with COQ10 also experienced less fatigue and increased muscle performance compared to placebo (Cooke 2008). These results support a previous study wherein CoQ10 supplementation (90 mg daily for 8 weeks) improved exercise performance in people with COPD (Fujimoto 1993).
Omega-3 Fatty Acids
Omega-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) help protect against damaging inflammatory reactions, build healthy cell membranes, and repair tissues (Calder 2012; Calder 2002; Odusanwo 2012). Omega-6 fatty acids, such as linoleic acid (LA) and arachidonic acid (AA), mediate pro-inflammatory activities (Calder 2002).
A study of clinically stable COPD reported that high dietary intake of omega-3 fatty acids decreased the risk of elevated blood inflammatory markers in COPD, while higher dietary intake of omega-6 fatty acids increased the risk of elevated inflammatory markers (de Batlle 2012).
EPA and DHA supplementation can reduce the destructive effects of chronic inflammation (Calder 2012). One study showed a significant improvement in shortness of breath and a decrease in inflammatory markers in serum and sputum in a COPD group receiving omega-3 supplementation compared with controls (Matsuyama 2005).
Cell culture and animal studies report that boswellic acids, specifically acetyl-11-keto-beta-boswellic acid (AKBA), from boswellia serrata can inhibit two enzymes involved in inflammation: 5-lipoxygenase (5-LOX) and cathepsin G (catG) (Siddiqui 2011; Abdel-Tawab 2011). 5-LOX stimulates the manufacture of pro-inflammatory leukotrienes and promotes the migration of inflammatory cells to the inflamed body area. 5-LOX has been shown to cause bronchoconstriction and promote inflammation (Siddiqui 2011). Cathepsin is a protein-degrading enzyme that attracts T cells and other leukocytes (white blood cells) at the sites of injury (Abdel-Tawab 2011). Animal studies showed that synthetic cathepsin inhibitors reduced smoke-induced airway inflammation (Maryanoff 2010) as well as airway hyperresponsiveness and inflammation (Williams 2009).
Studies in asthma suggest an anti-inflammatory role for Boswellia serrata in pulmonary disease. For instance, a randomized controlled trial showed that daily treatment with Boswellia serrata extract (BSE) increased the lung function of people with asthma compared to a control group (Gupta 1998).
Resveratrol, a molecule found in red wine, grapes, and Japanese knotweed, has antioxidant and anti-inflammatory properties that may protect against COPD and asthma (Wood 2010). A cell culture study found that resveratrol inhibited the release of all measured inflammatory mediators (cytokines) from immune cells extracted from the alveoli of smokers and non-smokers with COPD. In contrast, the corticosteroid dexamethasone did not inhibit the release of some cytokines in smokers with COPD (Knobloch 2011). Moreover, while resveratrol attenuated the release of inflammatory mediators in airway smooth muscle cells, it preserved signaling of a protein called vascular endothelial growth factor (VEGF), which may be protective against emphysema. Meanwhile, although corticosteroids significantly reduced inflammatory mediators, they also suppressed VEGF signaling (Knobloch 2010). In another study, resveratrol inhibited inflammatory cytokine release from alveolar macrophages in smokers and non-smokers with COPD in a dose-dependent manner (Culpitt 2003).
The concentration of zinc is lower-than-normal in people with COPD; the level is even lower in severe cases (Herzog 2011). A clinical trial showed that critically ill people with COPD spent significantly less time on mechanical ventilation after receiving an intravenous cocktail of selenium, manganese and zinc, compared to those who did not (El-Attar 2009). Another study demonstrated that treatment with 22 mg of zinc picolinate for 8 weeks significantly increased the levels of an important antioxidant, superoxide dismutase, in COPD patients (Kirkil 2008).
Respiratory infections increase the frequency and severity of exacerbations. L-carnitine modulates immune function, supports fatty acid and glucose metabolism, and may prevent wasting syndrome (Manoli 2004; Ferrari 2004; Alt Med Rev 2005; Silverio 2011). In one clinical trial, 2 grams of L-carnitine daily improved exercise tolerance and the strength of respiratory muscles in people with COPD. Blood lactate level, which is associated with muscle fatigue, was also reduced with L-carnitine supplementation (Borghi-Silva 2006; Cooke 1983).
Essential Amino Acids and Whey Protein
COPD is associated with muscle wasting and weight loss (i.e., sarcopenia, cachexia), especially in elderly people; and a higher degree of wasting predicts mortality in this population (Franssen 2008; Slinde 2005). Supplementation with essential amino acids, which are central to anabolic processes that help sustain muscle mass with advancing age, may help combat wasting in aging people with COPD (Dal Negro 2010). In a 12-week study involving 32 COPD patients aged 75 (mean) with impaired lung function, supplementation with 8 grams of essential amino acids daily lead to gains of body weight and fat free mass, as well as improved physical function and several biomarkers compared to placebo (Dal Negro 2010). Whey protein is a good source of essential amino acids and evidence indicates that whey protein may support muscle protein synthesis even more so than its constituent essential amino acids among an aging population (Katsanos 2008).
Poor sleep quality is prevalent among individuals with COPD, and oxidative stress is a significant contributor to lung deterioration and disease progression (Gumral 2009; Nunes 2008). Since the hormone melatonin is both a powerful antioxidant and a regulator of the sleep-wake cycle, it has received interest within the COPD research community for its potential to target these two important aspects of the disease (Pandi-Perumal 2012; Srinivasan 2009). Observational data indicate that melatonin levels decline and oxidative stress increases during COPD exacerbations (Gumral 2009). Clinical trials have shown that administering 3 mg of melatonin to COPD patients improves sleep quality and attenuates oxidative stress (de Matos Cavalcante 2012; Shilo 2000; Nunes 2008).