Nutrition in Cystic Fibrosis: Macro- and Micronutrients

Cystic fibrosis (CF) is the most common life-threatening autosomal recessive inherited disease in Caucasians, and is characterized by progressive lung disease, pancreatic insufficiency, malnutrition, hepatobiliary disease and elevated sweat electrolyte levels. The increased survival of CF patients during the past 20 years is the result of optimal nutrition, aggressive use of antibiotics, meticulous physiotherapy and exercise programs, and a better understanding of the disease. This thesis aimed to investigate the effect of exercise and nutrients on the physical condition of pediatric patients with cystic fibrosis. Chapter 1: Effects of anaerobic training in children with cystic fibrosis. Aerobic exercise programs have shown inconsistent effects on pulmonary function and suboptimal compliance. We found that high-intensity anaerobic training, mimicking children's natural activity pattern and containing the necessary variation, could enhance anaerobic and aerobic performance, and improve health-related quality of life in children with mild-to-moderate CF. Chapter 2: Short-term protein intake and stimulation of protein synthesis in stunted children with cystic fibrosis. Nutritional strategies in CF focus primarily on high-energy and high-fat intake, but not on optimal protein intake. The current recommendations of 1.0-1.5 g protein/kg/d, might be suboptimal, since a portion of the CF patients are stunted, and chronic inflammation and recurrent infections induce protein catabolism. Comparing 3 isoenergetic diets with different amounts of protein (1.5, 3 and 5 g protein/kg/d), we found a significantly higher whole-body protein synthesis in the group receiving the highest amount of protein. Chapter 3: Micronutrients Chronic pulmonary inflammation and infection combined with maldigestion and malabsorption cause oxidative stress. Chapter 3.1: Decreased Coenzyme Q10 concentration in plasma of children with cystic fibrosis. We found significantly diminished plasma concentrations of the lipid soluble antioxidant CoQ10, but a normal ratio between oxidized and reduced CoQ10, in CF patients with mild-to-moderate pulmonary disease. .Chapter 3.2: Dietary supplementation with multiple micronutrients mixture: no beneficial effects in pediatric cystic fibrosis. Since CF is characterized by both oxidative stress and poor exercise tolerance we investigated the effect of a mixture of multiple micronutrients (ML1) with either antioxidant and/or muscle fortifying action. We found no beneficial effects on either pulmonary function or anaerobic and aerobic muscle performance in pediatric cystic fibrosis patients compared to placebo. Chapter 4.1: Abnormal mechanical and energetic properties of skeletal muscle in a mouse model of cystic fibrosis. CF patients often demonstrate altered skeletal muscle performance and exercise intolerance. We found evidence of intrinsic abnormality in fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (SOL) muscles in a transgenic mouse, with a C57BL/6 background and the δF508 mutation, as compared to wildtype. A significantly lower absolute, but significantly higher specific isometric force (force per gram muscle) of twitch contraction was seen. Chapter 4.2: Influence of micronutrients on the contractile properties of skeletal muscle in a mouse model of cystic fibrosis. We could positively influence the 'altered' mechanical muscle performance in superfused, intact, fast-twitch EDL muscle of both wild-type FVB and transgenic FVB/ δF508 mice by direct administration of CoQ10, but not of vitamins B2 or E, nor a mixture of α-lipoic acid and acetylcarnitine