Definition

Cystic fibrosis (CF), also known as mucoviscidosis (from Latin mucus, "slime," and viscidus, "tenacious, sticky"), is a genetic, autosomal recessive metabolic disorder. It is one of the most common metabolic disorders among Caucasians. The disease is characterized by a malfunction in chloride channels, altering the composition of all exocrine gland secretions. This malfunction prevents the normal osmotic dilution of these secretions, making them thick and viscous. The glands in the bronchial tubes, pancreas, small intestine, liver, and sweat glands are particularly affected. In the bronchial tubes, the thick secretions create a favorable environment for pathogens like Staphylococcus aureus and Pseudomonas aeruginosa. Repeated lung infections can lead to progressive lung failure, potentially requiring long-term oxygen therapy or even a lung transplant ¹. With the development of potent modulator therapies targeting the defective CFTR protein, CF patients now live over 40 years longer than they did before the advent of these treatments. As a result, CF patients now face new challenges in managing comorbidities commonly seen in the aging population ².  

 In addition to lung function, nutritional status is one of the most important prognostic factors for CF patients. Pancreatic inflammation and fibrosis can lead to CF-related diabetes, a prevalent comorbidity that affects an estimated 20% of adolescents and up to 40-50% of adults   ² . Other gastrointestinal complications include hepatic steatosis (affecting 25-60% of patients) and cirrhosis (affecting about 10%), both resulting from bile duct obstruction. Approximately 65% of adult CF patients suffer from osteopenia, and 25% have osteoporosis ³  . Early diagnosis, prevention of malnutrition, and timely intervention are crucial for the success of nutritional therapy in CF. Recurrent infections, nutrient losses due to malabsorption, glucosuria in diabetic patients, and protein losses from large amounts of sputum contribute to high requirements for energy, protein, and micronutrients. Meeting these increased needs is challenging and should be a priority for the entire treatment team. 

Impact on metabolism and nutritional status 

Data on the prevalence of malnutrition in adult CF patients are limited. Depending on the criteria used, 42-49% of CF patients are classified as malnourished ^4,5 . Nutritional therapy is a critical intervention alongside medication, inhalation therapy, and physiotherapy. In CF, both exocrine and endocrine functions of the pancreas may be compromised. Approximately 85% of CF patients suffer from exocrine pancreatic insufficiency (EPI) ⁶, a condition that impairs digestion due to reduced secretion of pancreatic enzymes and bicarbonate. The irreplaceable deficiency of pancreatic lipase leads to malabsorption of dietary fats, proteins, starch, and fat-soluble vitamins (A, D, E, and K), resulting in malabsorption syndrome. Symptoms of untreated EPI include severe digestive disturbances such as steatorrhea, bulky and foul-smelling stools, flatulence, abdominal pain, and weight loss. The recommended treatment for CF patients with EPI includes a high-fat diet, pancreatic enzyme replacement therapy (PERT), and supplementation of fat-soluble vitamins ⁷. 

 CF patients exhibit mild hypermetabolism (5-35%) due to increased breathing effort, chronic inflammation, and recurrent infections   ⁸. The Harris-Benedict formula underestimates resting basal metabolic rate by about 23% compared to measurements from indirect calorimetry. For malabsorption, an additional 20-50% should be added to the resting basal metabolic rate, and if the patient is malnourished, a further 30% is recommended. International guidelines suggest that the total daily energy requirement for CF patients is 110–200% higher than for a healthy population of similar age, sex, and height ^{9, 10} . Protein requirements are also significantly higher—double that of a healthy population—and account for 20% of the total daily energy needs ^{4, 10, 11}.  

Nutrient requirements of cystic fibrosis patients. Adjustments are necessary for malnourished patients, physical activity and age of patients. The weight used is the adjusted body weight (AjBWJ) from BMI 28, otherwise body weight before hospital admission ³. BW = body weight; d = day

Aims of Nutritional Therapy

• Maintaining/improving nutritional status and bodily functions 
• Normalization of digestion and alleviation of symptoms 
• Prevention of malnutrition/nutrient deficiencies 
• Increase/optimization of food intake 
• Reduction of systemic inflammation and hypermetabolic stress 

Oral Nutrition

Nutrition plays an important role in patients with CF, which is why a nutrition assessment should be carried out every 3-6 months with the aim of preventing malnutrition. A protein- and energy-enriched diet (hypercaloric) helps to improve the nutritional status. If possible, nutritional counseling should be integrated at the beginning of nutritional therapy to address nutrition-related symptoms and optimize food intake. Key components of nutritional counseling include communicating the reasons for and goals of nutritional therapy. 
 
Malnourished CF patients should also enrich their food with additional fats (cream, butter/margarine, oil, nuts, etc.) and/or maltodextrin or protein powder. In particular, vegetable fats (e.g., canola oil, soybean oil, or walnut oil) should be used more liberally. Including snacks in the diet plan is also essential. If a positive energy balance cannot be achieved with a regular diet, nutritional supplements, such as energy- and protein-rich sip feeds, can help increase energy intake. 
 
Enteral nutrition: if more than 75% of energy and protein needs cannot be met with oral intake and supplements, enteral nutrition is recommended and should be escalated to supplemental enteral nutrition (via nasogastric or long-term PEG tube) after no more than 5 days. Complementary parenteral nutrition is indicated if less than 75% of the requirement can be covered by oral and/or enteral nutrition over a period of 10 days. For further details, please refer to the chapter on enteral and parenteral nutrition. 

Nutrition and CFTR modulator use

Patients taking a CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) modulator as medication every 12 hours (e.g. Trikafta®, Orkambi®, Symdeko®) should take it with a fatty meal or drink. This helps the body better absorb the active ingredients, tezacaftor and ivacaftor, contained in the medication. CFTR modulators contribute to the improvement/stabilization of lung disease and can also increase appetite and reduce basal metabolic rate, potentially leading to weight gain. 

Diagnosis of EPI and PERT

The direct Elastase-1 test, which measures the concentration of this enzyme in stool via ELISA, is suitable for the routine diagnostic determination of exocrine pancreatic insufficiency (EPI); the lower limit is about 200 μg elastase per gram of stool. The disadvantages are the low sensitivity (50-93%, also depending on the severity of pancreatic insufficiency) and specificity (62-93%) ¹² . The 13C breath test is more elaborate but has limited availability. It is more sensitive than fecal elastase (sensitivity and specificity after six hours 93% and 92%) ¹³ . Pancreatic enzyme replacement therapy (PERT) should be initiated immediately after diagnosing EPI. The treatment consists of encapsulated enzyme preparations containing extracts of porcine pancreatin in the form of acid-resistant microspheres of up to 2 mm in diameter and different amounts of lipase, usually 10,000 IU and 25,000 IU (e.g., Creon®, Panzytrat®; vegan option: Nortase®, derived from rice fungi). The recommended dosage is 50,000–75,000 IU for main meals and 10,000–25,000 IU for snacks. On average, 2,000–3,000 IU lipase per gram of dietary fat is required.  

For optimal enzyme effectiveness, the capsules should be taken throughout the meal with a small amount of liquid. Therapy response should be evaluated every three to six months based on clinical symptoms, such as steatorrhea, abdominal pain, bloating, and weight loss. However, normalization of digestion is not always achieved. Lack of therapeutic success may stem from uncertainty regarding the optimal dose and form of enzyme replacement, poor patient compliance, or inadequate treatment of comorbid conditions. If treatment fails, the diet should be reviewed, and the enzyme dose may be doubled. Proton pump inhibitors can be prescribed to prevent pH-dependent inactivation of the enzymes due to insufficient bicarbonate secretion. By increasing the pH of the duodenal/jejunal chyme to >7.0, PERT effectiveness can be significantly optimized ¹⁴

Monitoring

• Prolonged Catabolism: In cases of prolonged catabolism (from around 5 days), if artificial nutrition (enteral or parenteral) is indicated, it should be gradually increased over several days, with careful monitoring for refeeding syndrome. 
• Vitamin and Trace Element Levels: Blood levels of vitamins A, D, E, and K, as well as trace elements like zinc, iron, and selenium, should be monitored regularly—at least once a year, or 3-6 months after the last dose adjustment of the replacement therapy. 
• Vitamin A Monitoring with CFTR Modulators: Preliminary data suggest that vitamin A levels may increase with prolonged CFTR modulator use. Thus, regular checks of vitamin A blood levels are advised for patients on CFTR modulator therapy. 
• Bone Health: Due to the high prevalence of osteopenia and osteoporosis, it is recommended to monitor bone metabolism (DXA) every 2 to 3 years. 
• Diabetes Screening: To diagnose CF-related diabetes early, annual screening with the oral glucose tolerance test (OGTT) is currently recommended. HbA1c is not routinely recommended, as it may appear falsely normal in CF patients. 

Medications/Supplements 

• Pancreatic Enzyme Replacement Therapy: For exocrine pancreatic insufficiency, options include Creon®, Panzytrat®, or the vegan alternative Nortase®. 
• Proton Pump Inhibitors: If enzyme replacement therapy alone is insufficient, try co-medication with proton pump inhibitors. 
• Fat-Soluble Vitamin Supplementation: For exocrine pancreatic insufficiency, DEKAs® or DEKAs® Plus capsules are recommended. 
• Oral Rehydration Solutions: To address dyselectrolytemia and high salt loss, use solutions like Elotrans® or Oralpädon®. 
• CFTR Modulator Therapy: For specific genetic profiles, CFTR modulators (e.g., Trikafta®, Orkambi®, Symdeko®) can improve or stabilize lung function and promote weight gain. These medications should be taken with a fatty meal or drink. 
• Mucociliary Clearance: Enhance mucociliary clearance, prevent atelectasis, bronchiectasis, and pulmonary infections with inhaled respiratory physiotherapy, secretolytics, and beta-2 sympathomimetics (short- and long-acting). 
• Inhaled Antibiotics: Prevent exacerbations with inhaled antibiotics. 
• Systemic Antibiotics: Treat pulmonary infections as necessary. 
• Cholestasis and Hepatopathy: Treat cholestasis and prevent liver disease with ursodeoxycholic acid (Ursofalk® tablets). Note: In cases of cholestatic liver disease, consider substituting long-chain triglycerides with medium-chain triglycerides, which do not require pancreatic lipase or bile for absorption. 
• Distal Intestinal Obstruction Syndrome (DIOS): Evaluate treatment with macrogol for distal intestinal obstruction. 
• CF-Associated Diabetes: Assess the need for insulin treatment in CF-associated diabetes mellitus. 

Insufficient Clinical Data

• Essential Fatty Acids: The essential fatty acids alpha-linolenic acid (omega-3 fatty acids, especially EPA and DHA from fish and algae) and linoleic acid (omega-6) are beneficial for maintaining cell membrane integrity and elasticity, which can positively influence inflammatory processes. While there’s insufficient evidence for a clear recommendation, it’s advisable to include 1-2 servings of fish per week, especially fatty fish like wild salmon, herring, and mackerel. 
• Probiotics: The current evidence on probiotics is inconsistent, so no definitive recommendation can be made. However, probiotics may be taken at two-hour intervals during antibiotic therapy to prevent diarrhea. Specifically, Lactobacillus rhamnosus GG and/or Saccharomyces boulardii, at a daily dose of 5–40 billion CFU, have shown effectiveness.