Evolution of Nutritional Management in Cystic Fibrosis
Cystic Fibrosis (CF) is the most common autosomal recessive genetic disorder affecting around 10,500 people in the UK (1).
CF is caused by mutations of the CF transmembrane conductance regulator (CFTR) gene which regulates the flow of water and chloride ions in and out of cells. There are over 2000 mutations of the CFTR gene. People with CF experience a build-up of thick sticky mucus primarily in the lungs, sweat glands, gut and pancreas (and other organs) causing inflammation, obstruction, and destruction of small ducts in the affected organs. a wide range of challenging symptoms affecting the entire body (2)
Nutritional management has always been an essential aspect of multidisciplinary care in CF from birth through to adulthood. Previously, poor growth and malnutrition were common features and considered to be inevitable consequences of CF. However, with advances in clinical and nutritional care over the last 8 decades, this is no longer the case (3).
In 1938 Dr Dorothy Andersen first described CF based on autopsy findings of children dying of malnutrition and called it “Cystic fibrosis of the pancreas” with vitamin A deficiency as being the likely cause. Andersen advised a low-fat high protein diet, vitamin A supplementation and pancreatic enzymes (4). Life expectancy was believed to be around 6 months and the focus of nutritional management was to control fat malabsorption and ease abdominal discomfort.
Infants and children continued to be fed this rather unpalatable diet and with advancements in clinical care including the first documented use of the antibiotic penicillin in 1944, life expectancy began to improve (5). However, with worsening chest symptoms and subsequent increase in energy demands, it was proving difficult to achieve and maintain normal growth. Nutritional management gained interest in the 1970s. Accurate measurements of energy intake revealed that many children had very poor nutritional intakes (6). The degree of underweight in children with CF was inversely correlated with survival which prompted more close monitoring. Various unappetizing supplements were tried with modest success for example “The Allan Diet”, consisting of beef serum protein hydrolysate, glucose polymer, and medium-chain triglycerides (7).
In 1972, Dr Douglas Crozier, from Toronto abandoned the traditional CF low-fat diet in favour of a high saturated fat diet of whole milk, butter, eggs and animal fats along with up 100 enzymes daily (9). Later a landmark paper highlighted the better survival of these patients (30 years versus 21 years) when compared with a similar group from Boston (who had followed the traditional low-fat diet) attributed this to their better nutritional state (10).
The high energy, high fat “CF Diet” has been the cornerstone of CF dietary management over the last 3 decades and along with advances in clinical care has resulted in improved nutritional status and survival. Furthermore, the introduction of newborn screening since the 1980s facilitates early diagnosis and effective treatment resulting in better growth (11).
Current nutritional management guidelines for CF aim to ensure that infants and children grow normally achieving the 50% percentile by age of 2 years. In adults a median BMI of 22kg/m2 for males and 23 kg/m2 is recommended (12). These values are associated with better lung function and survival.
Energy requirements in CF vary widely are currently quoted to be 110-200% of those required by healthy people of the same age and gender. Individual assessment is therefore of paramount importance. Oral nutritional supplements and overnight enteral tube feeding may be required, and expert consensus provides guidance on when to consider additional nutrition support (12).
With improving life expectancy in CF concerns have been raised about the impact of diet high in saturated fats. This was highlighted by Smith and colleagues documenting the overreliance of saturated fats in the diets of CF children (13). Mono and poly-unsaturated fats may offer more cardio protection and should be encouraged as part of the high-energy diet (12).
More recently overweight and obesity are an emerging concern. Factors contributing to this include early diagnosis, improved medical therapies, focused nutritional management and the influence of western diets (14,15). These 2 recent studies highlight the link between overweight and obesity and increased risk of death from atheroschlerotic disease in the general population. Recent CF Nutrition Guidelines provide a framework for identification, assessment and management of dietary interventions based on BMI in adults and BMI percentiles in children (16).
The landscape of nutritional care continues to change for people with CF, especially with the introduction of new CFTR modulator therapies that target the genetic defect of CF. This has led to lung function improvement, reduction in pulmonary exacerbations and increase in weight. This is highlighted in a recent focused systematic review (17).
Possible causes of weight gain include improvement in absorption due to higher gut ph and hence enzyme function, improved appetite, improved gut CFTR function, decreased REE and increased fat intake as modulators need to be taken with fat containing food.
Although weight gain may be welcomed by some, concerns have been raised about the potential for excessive weight gain. The impact of CFTR modulators on long term nutritional outcomes is unknown. Indeed, this is a topic under debate amongst CF dietitians who are striving to be responsive and provide the appropriate and holistic support and education on diet and lifestyle changes to people with CF who may be unaccustomed to rapid weight gain.
It should be noted that CFTR modulators are not currently prescribed for all people with CF. This may be due to a lack of drug availability for specific mutations. Some people are unable to tolerate due to side effects or drug interactions. In some countries, health economics may dictate who has access to these precision medications. We still have a lot to learn and should continue to offer a tailored nutritional approach to individuals with CF to optimise their nutritional status.
- UK Cystic Fibrosis Registry 2019 Annual Data Report. (2020) [online] available from
https://www.cysticfibrosis.org.uk/the-work-we-do/uk-cf-registry/reporting-and-resources [Accessed 31st May 2021]
- Li, L. and Somerset, S. (2014) Digestive system dysfunction in cystic fibrosis: challenges for nutrition therapy. Digestive and Liver Disease, 46, pp. 865-874.
- Collins, S. (2018) Nutritional management of cystic fibrosis – an update for the 21st Paediatric Respiratory Reviews, 26, pp. 4-6.
- Andersen, D. (1938) Cystic fibrosis of the pancreas and its relation to celiac disease: a clinical and pathological study. American Journal of Diseases of Children, 56 (2), pp. 344- 399.
- Di Sant’Agnese, P., Andersen, D.(1946) Celiac Syndrome IV. Chemotherapy in infections of the respiratory tract associated with cystic fibrosis of the pancreas; observations with penicillin and drugs of the sulphonamide group, with special reference to penicillin aerosol. American Journal of Diseases of Children 72, pp.17-61.
- Chase, H., Long, M., Lavin, M. (1979) Cystic Fibrosis and Malnutrition. Journal of Pediatrics, 95 (3), pp. 337-347.
- Kraemer, r., Rudeberg, A., Hadorn, B., Rossi, E. (1978) Relative underweight in cystic fibrosis and its prognostic value. Acta Paedatrica, 67(1), pp. 33-37.
- Allan, J., Milner, J., Moss, D (1973) Nutritional supplementation in the treatment of cystic fibrosis of the pancreas. American Journal of Diseases of Children, 126, pp. 2-26.
- Khaw, K., Adeniyi-Jones, S., Gordon, D., Polombo, J., Suskind, R. (1978) Efficacy of pancreatic preparations on fat and nitrogen absorptions in cystic fibrosis. Pediatric Research, 12, pp. 437.
- Corey, M., Mclaughlin, F., Williams, M., Levison, H. (1988) A comparison of survival, growth and pulmonary function in patients with cystic fibrosis in Boston and Toronto. Journal of Clinical Epidemiology, 41(6), pp. 583-591.
- Farrell, P., Kosorok, m., Rock, M. (2001) Early diagnosis of cystic fibrosis through neonatal screening prevents severe malnutrition and improves long-term growth. Pediatrics, 107, pp. 1-13.
- UK Cystic Fibrosis Trust (2016) Nutritional Management of Cystic Fibrosis [online] available from https://www.cysticfibrosis.org.uk/the-work-we-do/resources-for-cf-professionals/consensus-documents[Accessed 31st May 2021].
- Smith, C., Winn, A., Seddon, P., Ranganathan, S. (2012) A fat lot of good: balance and trends in fat intake in children with cystic fibrosis. Journal of Cystic Fibrosis, 11(2), pp. 154-157.