Nutritional countermeasures, coupled with other good health habits, should be implemented when COPD is diagnosed. Second of a two-part article.

Patients with advanced COPD must cope with an imbalance between energy supply and energy demand. Caloric intake is typically diminished, while metabolic demands are increased. The net effect is progressive malnutrition. Caloric and protein enhancement improves respiratory muscle function, although maximal inspiratory and expiratory pressures may be equivalent.

While the ideal substrate mixture to be administered to COPD patients is yet to be established, high-fat formulas have been advocated. Two independent lines of thought support this position. First, fats are high in caloric value, so small intake volumes deliver the required caloric values. Small food volumes limit abdominal distention, minimizing upward pressure on the diaphragm and lessening the sensation of dyspnea, as compared with higher volume feedings. Second, fats produce less carbon dioxide than does a carbohydrate-rich diet. Since carbon dioxide must be eliminated through respiration, breathing would be stimulated in an already compromised lung; if the lung reserve is inadequate, carbon dioxide retention may occur. The proposed benefit of altering the carbohydrate-to-fat ratio has not been substantiated in the literature, however. Long-term administration of high-caloric diets with approximately 55% carbohydrates (at levels twice that of resting energy expenditure) has not produced measurable changes in resting energy expenditure, dyspnea indices, or blood PCO2 in stable COPD patients. Protein supplementation can result in increased oxygen consumption from the thermic effect, increasing minute ventilation and altering the ventilatory response to hypoxemia and hypercarbia, leading to increased dyspnea. Studies confirming this deleterious effect are, however, absent from the literature.

Total caloric intake should be increased to at least 150% of baseline dietary intake, and carbohydrate loads of up to 300 g in a single meal are usually well tolerated. To meet protein needs and spare nitrogen wasting, about 20% of the diet should be protein, or 1.5 g per kg of body weight.22 For patients who are severely stressed or nutritionally depleted, protein needs to increase to 1.5 to 2 g per kg.22 Further, micronutrients and other trace elements, especially those most closely associated with muscle function, inflammation, and cellular repair, should be replaced.

Nutritional Support
Nutritional support should begin with a dietary counseling program. This evaluation can be extended to include biochemical and metabolic assessments, if warranted. Some clinicians and nutritionists advocate adding high-energy drinks to the patient’s usual dietary intake.23 Recently, high-energy food supplements have emerged. These supplements offer high caloric content in a small volume of food. Both drinks and food supplements have, however, been studied23,24 with conflicting results.

The duration of nutritional support is not well delineated in the literature. Short-term supplementation (for 2 to 4 weeks) in patients weighing less than 90% of the ideal body weight is yielding promising results. One study24 that investigated caloric supplementation (48% above baseline caloric consumption) over a 3-month period found that body weight increased an average of 4.2 kg, respiratory muscle strength improved, and dyspnea and well-being scores improved. There is a need for additional well-designed, randomized, short-term and long-term trials to identify the best supplementation or feeding regimen for the COPD patient and to quantify its optimal duration. Patients need to track their body weight; for some, compartmental analysis may provide the required information for tailoring a high-quality nutritional intervention.27

Nutrient Needs
The ideal substrate mixture to supplement normal oral consumption has not been established. High-fat supplements appear well suited for hospitalized patients because of the reduced carbon dioxide load and the high caloric delivery in small volumes. Macronutrient distributions of close to 50% fat have been used with success.28 Less is known about long-term use of these supplements. Protein supplementation has both positive and negative effects on the COPD patient. A balanced nutritional approach is recommended.

The micronutrient profile is beginning to attract considerable scientific interest. While specific micronutrient needs for the COPD patient are not established, it is essential that patients receive adequate quantities of vitamins, minerals, and trace elements based on US Department of Agriculture (USDA) Recommended Dietary Allowances (RDA) and USDA Adequate Intakes as goals for nutrient intakes. Some suggest that the RDA allocations are minimal requirements, especially when applied to a COPD patient with advanced disease and ongoing acute exacerbations. There is much that is still unknown about optimizing nutrition for COPD patients (and for other chronic disease cohorts).

Potassium, phosphorus, calcium, and magnesium are essential components of lean tissue, along with protein. Disturbances in electrolytes (hypophosphatemia, hypokalemia, and hypocalcemia) can adversely affect muscle function. If the diaphragm and accessory muscles lose contractile capacity, the ability to breathe is compromised. Reversing the deficiencies can restore function, can shorten medical lengths of stay, and may enhance quality of life.

Smoking has many deleterious effects on vitamin A. Smoking destroys retinol in plasma and destroys lung tissue responsible for uptake of vitamin A into lung cells, thereby promoting vitamin A deficiency. Supplementation with retinyl palmitate, in doses of 3,300 to 25,000 IU of vitamin A per day for 30 to 60 days, has produced improvements in pulmonary function and other indices.29

b-Carotene in patients with COPD, and especially in those who continue to smoke, is contraindicated. While b-carotene is an antioxidant, the effect of carotenoids can, in some instances, shift pro-oxidant activity toward a less favorable position. The shift is dependent on factors such as oxygen tension and carotenoid concentration. In smokers, supplementation with b-carotene was associated with an 8% increase in relative risk of death among smokers who received supplementation for 5 to 8 years.30 In a separate trial31,32 investigating the effects of b-carotene (30 mg per day) and retinyl palmitate (25,000 IU per day) on cancer chemoprevention, the relative risk of death by lung cancer increased 17% in the heavy smokers supplemented with B-carotene, compared to placebo. Based on these and other data, the use of b-carotene supplementation as a source of vitamin A is not warranted.

Vitamin C is the main antioxidant on the surface of the airways, and its presence is diminished by smoke exposure and/or chronic inflammation. Because vitamin C is a strong antioxidant and because of its location in the respiratory system, some suggest that supplementation should be beneficial in reestablishing an optimal oxidant-antioxidant balance, but this is yet to be proven.

Other nutrients may impart a protective effect through the intake of food (especially fruits and vegetables). This is especially noteworthy because it suggests that vitamin C supplementation alone will not suffice. For example, while the protective effects of fruit ingestion are attributed to vitamin C intake, some suggest that the protective effect is actually the result of the intake of solid fruit that contains other nutrients.33

Vitamin E is a potent antioxidant that functions, in part, by protecting other nutrients from destructive oxidation. Recent evidence34 indicates that vitamin E is protective as an antioxidant for individuals with COPD. Reduced levels of major plasma antioxidants (vitamin E and ascorbic acid) have been demonstrated in the lung lavage results of smokers, compared with nonsmokers. Daga et al35 have demonstrated that 400 IU of vitamin E, administered daily for 12 weeks, reduced lipid peroxidation by 42.8%.

While women experience a more profound loss of calcium from the bone matrix following menopause, men with COPD are also at high risk from bone demineralization. Smoke exposure, commonly present in patients with COPD, is associated with osteoporosis. Corticosteroids accelerate bone calcium loss and promote muscle wasting and water retention. Therefore, it is important that clinicians consider calcium replacement as part of the overall nutrition-management plan. Recent evidence suggests that biphosphonates36,37 should be added to stimulate enhanced bone mineralization when sufficient calcium and vitamin D are present. Smoking cessation, hormone therapy, and weight-bearing exercise training aid in preventing and controlling calcium loss and should be instituted in the overall treatment plan.

Increasing consumption of fruits, vegetables, and fish has been advocated for improving cardiovascular and oncological health and for assisting in maintenance of normal body weight. There is a suggestion, derived using epidemiological methods, that consumption of fruits, vegetables, and fish is protective. Tabak et al38 noted that 67% of the variance in COPD mortality is explained through food intake. Other investigators39,40 note similar findings. It is hypothesized that fruits and vegetables exert their protective effect by increasing the available antioxidants, thus protecting the airway by scavenging oxidant radicals before they damage cell lines in the lung and bronchioles. Consumption of fish rich in w-3 fatty acids replaces the proinflammatory w-6 fatty acids entering the arachidonic acid cascade, thereby altering the entire cascade. This substitution favorably alters prostaglandins, leukotrienes, and thromboxane to a less inflammatory state.39,40

Anabolic Agents
Evidence41 shows that human growth hormone, delivered at physiological doses, increases lean muscle mass and decreases fat mass, with no changes in functional capacity. Other studies23,42,43 have shown that administration of anabolic steroids and growth hormone increases muscle mass without producing significant clinical or biochemical side effects when administered for 3 to 27 weeks. These data suggest that other interventions (such as rehabilitation) must accompany the use of anabolic agents and good nutrition to produce significant changes. Anabolic steroid use is not without side effects that may include subcutaneous edema, diffuse arthralgia, impaired glucose tolerance, hypertension, cardiovascular disease, malignancies, and increases in energy expenditure. Therefore, the use of these agents is not advocated for the COPD cohort except under research applications.

Leptin
Leptin, produced in the fat reservoir, is an adipocyte-derived hormone that generates afferent signaling to the brain for the regulation of fat mass. Leptin is also involved in lipid metabolism and glucose homeostasis; it increases thermogenesis and affects T-cell–mediated immunity.44,45 It has been reported46 that serum leptin levels are reduced in patients with COPD. Lower leptin levels have been reported by Schols et al,47 who noted that emphysema patients had lower BMIs and fat masses than chronic bronchitis patients. These studies suggest a physiological regulation of leptin, independent of TNF and a cytokine-leptin link in emphysema patients.

Summary
Weight loss (specifically, loss of muscle mass) contributes significantly to the morbidity and mortality associated with COPD progression. Nutritional interventions focused on restoring nutritional deficiencies are essential. Increasing caloric consumption can restore body weight and can improve respiratory and skeletal muscle function, thus alleviating morbidity. When nutritional interventions are coupled with rehabilitation, results may be extended for some individuals. Nutritional replenishment should include not only excess calories in the correct macronutrient amounts, but key micronutrients essential for preserving and/or improving cell function and reducing the inflammatory process through direct (radical-scavenging) and/or indirect (immune) processes. Nutritional countermeasures, coupled with other good health habits, should be implemented when COPD is diagnosed. This continuous care model should be continually upgraded to optimize function and the nutrient delivery essential for a given individual. Clearly, we are only beginning to learn the true potential that nutrition has for preventing and treating COPD.


Padmini Shankar, PhD, RD, is associate professor of nutrition and dietetics and Jim McMillan, EdD, is associate professor of nutrition and health sciences at the Jiann-Ping Hsu School of Public Health, Georgia Southern University, Statesboro, Ga. Rick Carter, PhD, MBA, is professor and chair of the Jiann-Ping Hsu School of Public Health.

References
22. Pingleton SK. Enteral nutrition in patients with respiratory disease. Eur Respir J. 1996;9:364-370.
23. Schols AM, Soeters PB, Mostert R, Pluymers RJ, Wouters EF. Physiologic effects of nutritional support and anabolic steroids in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1995;152:1268-1274.
24. Efthimiou J, Fleming J, Gomes C, Spiro SG. The effect of supplementary oral nutrition in poorly nourished patients with chronic obstructive pulmonary disease. Am Rev Respir Dis. 1988;137:1075-1082.
25. Goldstein SA, Thomashow BM, Kvetan V, et al. Nitrogen and energy relationships in malnourished patients with emphysema. Am Rev Respir Dis. 1988; 138:636-644.
26. Rogers RM, Donahoe M, Costantino J. Physiologic effects of oral supplemental feeding in malnourished patients with chronic obstructive pulmonary disease. Am Rev Respir Dis. 1992;146:1511-1517.
27. Mador M. Muscle mass, not body weight, predicts outcome in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2004;166:787-788.
28. Angelillo V, Bedi S, Durfee D, et al. Effects of low and high carbohydrate feedings in the ambulatory patient with chronic obstructive pulmonary disease. Ann Intern Med. 1985;103:883-885.
29. Edes TE, Kwan SM, Buckley CS. Carcinogen-induced tissue vitamin A depletion. Potential protective advantages of beta-carotene. Int J Cancer. 1992;50:99-102.
30. Rautalahti M, Virtamo J, Haukka J. The effect of alpha-tocopherol and beta-carotene supplementation on COPD symptoms. Am J Respir Crit Care Med. 1997;156:1447-1452.
31. Paiva SA, Godoy I, Vannucchi H, Favaro RM, Geraldo RR, Campana AO. Assessment of vitamin A status in chronic obstructive pulmonary disease patients and health smokers. Am J Clin Nutr. 1996; 64:928-934.
32. Biesalski HK, Stofft E. Biochemical, morphological, and functional aspects of systematic and local vitamin A deficiency in the respiratory tract. Ann NY Acad Sci. 1992;669:332-336.
33. Miedema I, Feskens EJM, Heederik D, et al. Dietary determinants of long-term incidence of chronic nonspecific lung disease; the Zutphen Study. Am J Epidemiol. 1993;38:37-45.
34. Pacht R, Kaseki H, Mohammad JR, et al. Deficiency of vitamin E in the alveolar fluid of cigarette smokers. J Clin Invest. 1986;77:789-796.
35. Daga MK, Chhabra R, Sharma B, Mishra TK. Effects of exogenous vitamin E supplementation on the levels of oxidants and antioxidants in chronic obstructive pulmonary disease. J Biosci. 2003;28(1):7-11.
36. Worth H, Stammen D, Keck E. Therapy of steroid-induced bone loss in adult asthmatics with calcium, vitamin D, and a diphosphonate. Am J Respir Crit Care Med. 1994;150:394-397.
37. Meunier PJ, Arlot MA, Chavassieux P, et al. The effects of alendronate on bone turnover and bone quality. Int J Clin Pract. 2003;101(suppl):14-17.
38. Tabak C, Feskens EJM, Heemerik D, et al. Fruit and fish consumption: a possible explanation for population differences in COPD mortality (The Seven Countries Study). Eur J Clin Nutr. 1998;52:819-825.
39. Carroll KK. Biological effects of fish oils in relation to chronic diseases. Lipids. 1986;21:731-732.
40. Kelley VE, Ferretti A, Izui S, Strom TB. A fish oil diet rich in eicosapentaenoic acid reduces cyclooxygenase metabolites, and suppresses lupus in MRL-1pr mice. J Immunol. 1985;134:1914-9.
41. Pape GS, Friedman M, Underwood LE, et al. The effect of growth hormone on weight gain and pulmonary function in patients with chronic obstructive pulmonary disease. Chest. 1991;99:1495-1500.
42. Casaburi R, Goren S, Bhasin S. Substantial prevalence of low anabolic hormone levels in COPD patients undergoing rehabilitation. Am J Respir Crit Care Med. 1996;153(4):A128.
43. Shizgal HM. Anabolic steroids and total parenteral nutrition. Wien Med Wochenschr. 1993;143:14-15.
44. Auwerx L, Staels B. Leptin. Lancet. 1998;351:737-742.
45. Lord G, Matarese G, Howard J. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature. 1998;394:
897-901.
46. Takabatake N, Nakamura H, Abe S. Circulating leptin in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999;159:1215-1219.
47. Schols AM, Creutzberg EC, Buurman WA, Campfield LA, Saris WH. Plasma leptin is related to proinflammatory status and dietary intake in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999;160:1220-1226.