Gastrointestinal Symptoms and Nutritional Deficiencies in Cystic Fibrosis Patients

by | Apr 18, 2016 | Cystic Fibrosis, Lung Health

Written by Tatjana Djakovic, Staff Writer. This article discusses the role of diet and nutrient supplementation in the treatment of cystic fibrosis.

The diet of cystic fibrosis patients plays an integral part in their longevity and staying free of symptoms. At the time of diagnosis, only 15% of patients have normal pancreatic function for fat digestion, which decreases over time to more than 90% of CF infants and younger children displaying insufficiency. Although there have been many improvements in the treatment of cystic fibrosis, the problem of intestinal malabsorbtion persists despite pancreatic enzyme replacement therapy. The pancreatic abnormalities are caused due to an obstruction of small ducts by thick, sticky mucosal secretions. There is a defect in fluid secretion such as water which leads to high protein concentration in the pancreatic juice leading to blockage of small pancreatic ducts and to degradation of pancreatic tissue. Progressively, there is a conversion of normal structure of the pancreas as the number of normal functional cells is lost. The loss of pancreatic enzymes results in a reduced capacity to digest food which leads to nutritional deficiencies (1).

The CFTR protein in the intestines is responsible for keeping a balance between fluids (e.g. water) and ions particularly chloride and bicarbonate. In the case of cystic fibrosis, the mutated protein causes an abnormally low volume of fluid and irregular electrolyte composition. A decrease in anion and fluid transport caused by the loss of CFTR function, results in a dehydrated intestinal environment, and a prolonged acidity in the small intestine after a meal has been consumed.

When CFTR is not present, gastric acid is not properly neutralized in the intestines resulting in poor digestive function in the intestine. Due to the altered luminal environment, there is an accumulation of mucus in the CF intestine. In addition, to the intestines and the stomach, cystic fibrosis related liver disease occurs in 5% to 15% of the patients usually in the first decade of life. However, even in patients that do not have clinical liver disease, there is a fecal loss of bile acids which leads to poor absorption ultimately contributing to fat and vitamin malabsorption (2)

The GI tract of healthy individuals is home to a wide variety of bacteria and contributes to the bulk of the fecal material. In patients with CF, the GI microbiota is altered in diversity, location, and cell density. Normally, healthy bacterial levels are maintained through actions of gastric acid, peristalsis, intestinal fluid, antibacterial proteins. If any of these mechanisms fail, it can lead to bacterial overgrowth of the small intestine, which can lead to diarrhea, abdominal distention, flatulence, steatorrhea, anemia, and weight loss. The weight loss results from bacterial competition for ingested nutrients, intestinal inflammation, and reduces the ability to emulsify fat.

The nutritional needs of cystic fibrosis patients is more complex due to their higher energy needs resulting from a malabsorption of nutrients, including fat and fat soluble vitamins as well as the increased work of breathing as lung function declines. Researchers have recognized the connection between nutrition and lung function and have worked hard to develop the ideal diet which would maximize lung function.

The absence of normal CFTR function contributes to accumulation of mucosal secretions and obstruction of pancreatic ducts which leads to destruction of pancreatic cells, fibrosis and ultimately the inability of pancreatic enzymes to enter the duodenum and digest food. In addition, there is low stomach pH since there is not enough bicarbonate being secreted which results in precipitation of bile salts. Therefore, the combination of enzymatic activity and inadequate bile salts leads to malabsorption of nutrients, including fat and fat-soluble, resulting in failure to thrive.

Compared to the controls, children with cystic fibrosis have been found to have increased resting energy expenditure. It has been hypothesized that the majority of people who have an increased energy expenditure due to a malfunctioning CFTR protein that alters the normal metabolism.

Nutrition therapy

The goal of nutrition therapy is to promote optimal growth and development, lean body mass and weight maintenance, increased muscle strength and development and improved survival. The factors that contribute to a high quality diet include high calorie, high-protein unrestricted diet, enzyme therapy, and supplemental nutrition.

Early efforts in nutritional management of cystic fibrosis focused on providing a low-fat diet in order to decrease the effects of malabsorption, but the development of enteric coated enzymes in the 1970’s to provide increased calories and essential fatty acids. Since fat loses occur, even with optimal enzyme therapy, and can be as much has 10%-20% compared to <5% in healthy controls, it is recommended that 40% of total calories come from fat. (3) In addition, 20% of calories should come from protein. (3)

In order to improve calorie and fat intake, it is recommended to provide patients education to maximize calorie and protein intake and meals and snacks, encourage small frequent meals, using calorie dense commercial supplements or homemade milk shakes, and promoting regular aerobic exercise to enhance appetite.(4)

A high salt diet is also recommended as salt losses in the sweat of individuals with CF can be 2 to 5 times normal.(5)

Fat Soluble Vitamins

In pancreatic-insufficient individuals, steatorrhea (fat loss in the feces) presents with fat soluble vitamin loss particularly A, D, E, and K. These vitamins are very important because they are involved in immune function, normal bone development, antioxidant properties, and are needed to increase the ability of the body to fight off acute and chronic pulmonary infections. (6)

Vitamin A

Vitamin A is best known for its role in vision but it is also essential for regulation of the immune system. The Cystic Fibrosis Foundation recommends maintaining an intake of 1500 to 10,000 IU of retinol per day.(7)

Vitamin D

Vitamin D is most important for calcium metabolism and bone mineralization, but more recently it ahs been found to play a role in muscle function, immunity, cardiovascular disease, diabetes, and some cancers. It was reported that approximately 90% of patients with CF and 74% of controls were reported to be vitamin D insufficient with serum levels below 30 ng/dl despite routine supplementation.(8)

The cystic fibrosis foundation recommends daily doses of 400 to 800 IU to maintain 25(OH) D levels greater than 30 to 60 ng/ml.(9)

Vitamin E

There are 8 compounds with vitamin E biological activity. Alpha-Tocopherol is the most active and the one measured in plasma. Vitamin E is known for its antioxidant properties as a free radical scavenger and is essential for a normal functioning immune system, which is necessary for patients with CF.(10)

Vitamin K

Vitamin K deficiency has often been reported in cystic fibrosis patients.(11) The possible reasons for the deficiency include:

  • Reduced absorption of fat due to insufficient pancreatic enzymes
  • Liver disease
  • Reduced production of vitamin K by the intestinal bacteria due to many antibiotic treatments
  • Increase mucus accumulation in the bowel.

The prevalence of vitamin K deficiency in cystic fibrosis patients is high. In a study consisting of 98 cystic fibrosis patients and 62 healthy individuals with no previous intake of vitamin K supplements, it was determined that 78% of pancreatic insufficient patients had lowered vitamin K levels (11). This was measured by detecting the levels of defective proteins such as coagulating factors and proteins involved in bone formation known as the PIVKA-II test (prothrombin in vitamin K absence).

Following this preliminary study, a new study was conducted to investigate the effect of intake of fat soluble vitamin combination supplement A,D,E, and K on vitamin K deficiency. The study consisted of 78 cystic fibrosis patients of which 81% had abnormal vitamin K levels. The supplement was given for a minimum of 4 months and the mean vitamin K intake was 0.18 mg per day. After supplementation 29 (40%) had higher vitamin K levels (P=0.001), which means that in more than half of the patients were able to obtain normal vitamin k levels.

Recommendations from Europe and UK have suggested that doses of vitamin K ranging from 0.3mg per day to 10 mg per day are necessary for cystic fibrosis patients. (12, 13) The deficiency of Vitamin K decreases the liver’s production of vitamin K dependent coagulation factors which are needed to coagulation of blood which predisposes cystic fibrosis patients to easy bruising, bleeding and potentially life threatening hemorrhage. (14)

The cystic fibrosis patients most at risk of having bleeding problems are those with liver disease and those that are not receiving pancreatic enzymes. The body is capable of maintaining normal vitamin K concentration in the tissues because it obtains it from the circulation blood, however it does not do as great of a job in maintaining normal bone density.

Several studies have examined the relationship between the vitamin K supplementation and levels of osteocalcin a bone forming protein since optimal dosage if difficult to determine. For example, a one year of vitamin K supplementation (10 mg vitamin K1 per week) resulted in increased levels of osteocalcin in group of cystic fibrosis school children (15). Another study, Drury et al. 2008 (12) investigated 14 children with similar ages receiving either 1 or 5 mg per day vitamin K1 for one month which resulted in normalization of vitamin K levels in only 3 of the 14 children.

Due to inconclusive evidence on the dosage of vitamin K supplementation for cystic fibrosis patients, a review of the current literature was performed which mainly focused on two randomized controlled trials. The first was done by Beker et al. 1997 (16) which included 18 patients between the ages of 13 and 35 years in which patients were given 5mg of vitamin K1 per week. In the second trial mentioned above by Drury et al. 2008, 14 patients were included in the trial between the ages of 8 to 18 years were given 1mg per day for a period of 1 month. In both trials the vitamin K levels returned to normal after 1 month supplementation.

Posted April 9, 2015.

References: Use numbers to correspond to the numbers in the copy above.

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