Why bother to take vitamins?
Authors: Alison Morton
Journal: Journal of the Royal Society of Medicine (2011)

The first clear description of ‘fibrocystic disease of the pancreas’ or Cystic Fibrosis (CF) came in the late 1930s1 and evidence of vitamin A deficiency was reported in 10 of 49 patients as early as 1939.2 Indeed, this paper recommended ‘generous dosages’ of vitamin A for these patients.

Biochemical evidence of fat-soluble vitamin deficiency occurs early in infants diagnosed with CF by newborn screening.3–6 Sokol et al. reported the fat-soluble vitamin status of 36 infants diagnosed by newborn screening between 1984 and 1987 with the initial evaluation being undertaken at around seven weeks of age. There was an inverse correlation between three-day faecal fat excretion and serum α-tocopherol levels (vitamin E). Twenty-one percent of patients had low vitamin A levels, 35% low vitamin D, 38% low vitamin E and vitamin E:lipid ratio though none had an elevated PIVKA-II (protein induced by vitamin K absence or antagonism) – one indicator of vitamin K deficiency. Introduction of pancreatic enzyme replacement therapy, and standard fat-soluble vitamin supplementation corrected vitamin A and D status at 6 and 12 months of age. However, 10% of patients remained vitamin E deficient.3

Feranchak et al. reported that 44 of 96 (45.8%) infants diagnosed by newborn screening between 1984 and 1997 had a deficiency of one or more of the fat-soluble vitamins by 4–8 weeks of age. Vitamin A deficiency occurred in 29% of patients, vitamin D deficiency in 22.5% and vitamin E deficiency in 22.8%.4 Bines et al. reported low serum retinol in 20 out of 39 (51%) infants and low α-tocopherol in nine of 38 (24%) infants diagnosed by newborn screening between 1991 and 1994.5

These studies are supported by more contemporaneous data. Neville and Ranganathan reported 58 infants diagnosed by newborn screening between 2001 and 2006. Median age of diagnosis was 1 month (range 0–3 months). Vitamin D deficiency was described in 11 of 30 infants (37%), vitamin E deficiency in seven of 45 (16%) and vitamin A deficiency 27 of 45 (60%). Vitamin A and E levels were significantly lower in pancreatic insufficient patients. Vitamin A and E status was significantly correlated with pancreatic status though there was no significant correlation with pancreatic status and vitamin D deficiency.6

Why bother to take vitamins? Firstly, because at the time of diagnosis of CF there is clear biochemical evidence of vitamin A deficiency in up to 60% of infants6 and vitamin D and E deficiency in up to 37%6 and 38%,3 respectively. Untreated, the incidence of biochemical and later clinical vitamin deficiencies will increase.

Most people with CF are at risk of fat-soluble vitamin deficiencies due to fat malabsorption and maldigestion as a consequence of pancreatic insufficiency and bile salt deficiency. Patients treated with pancreatic enzyme replacement therapy may still experience refractory steatorrhoea due to enzyme inactivation as a consequence of high intestinal pH, small bowel bacterial overgrowth,7 the presence of a mucus barrier lining the intestine, short gut syndrome due to previous bowel resection and CF-related liver disease. Adherence rates are difficult to assess8 but non-adherence to pancreatic enzyme replacement is commonly reported9,10 and contributes to malabsorption. We know that some patients do not bother to take their prescribed vitamins as adherence rates in people with CF of 47% of the recommended vitamin prescription have been reported.9,11 Modi et al. compared different methods of assessing adherence to vitamin therapy. Adherence was variable and ranged from 22% when recorded in a diet diary to 94% for self-report by children.10 Non-adherence to therapy, poor dietary intake either due to anorexia or poor dietary sources of vitamins can also contribute to fat-soluble vitamin deficiency in CF. All of these factors put people with CF at high risk of vitamin deficiencies and in addition there are vitamin-specific risk factors detailed below.

Advances in the clinical and medical management of people with CF have led to improved life expectancy and new and emerging co-morbidities. The introduction of newborn screening allowing for earlier and more aggressive intervention together with improved pancreatic enzyme replacement therapy, the early introduction of appropriate fat soluble vitamin supplementation and an overall improvement in nutritional status together with advances in our understanding of fat-soluble vitamin metabolism12 mean we need to consider fat-soluble vitamin status in the context of modern disease. The emphasis of how vitamin status is defined has shifted. Traditionally vitamin status was discussed in terms of overt deficiency resulting in the classically recognized deficiency symptoms such as night blindness and xeropthalmia in vitamin A deficiency. Now vitamin status is also considered in terms of subclinical deficiencies which are defined as low serum, tissue or airway surface liquid vitamin levels with no visible signs or symptoms of deficiency. It is increasingly recognized that subclinical deficiencies in CF may play a significant role. Vitamin status may now be considered in the context of health outcomes rather than overt deficiency12 with levels being described as deficient, insufficient, adequate, optimal and toxic.