Quote from tim on September 11, 2020, 7:31 am

Zinc therapy for night blindness in cystic fibrosis

Zinc is absorbed by enterocytes in the proximal small intestine, and zinc deficiency has been associated with malabsorption syndromes such as CF [4]. In CF, unabsorbed fat specifically interferes with the re-absorption of endogenous zinc [5], and this, together with prior small bowel resection, may have contributed to the zinc deficiency in this case. Furthermore, iron supplementation has been shown to inhibit zinc absorption in the human small intestine [6].

The knowledge of zinc metabolism in the eye is fragmentary. Much of the evidence for its role in retinal function comes from interaction studies with other nutrients, a few naturally occurring diseases and in vitro studies [4]. It is known that zinc interacts with taurine and vitamin A in the retina, modifies plasma membranes in the photoreceptors, regulates the light-rhodopsin reaction within the photoreceptor, modulates synaptic transmission and serves as an anti-oxidant in both the retinal pigment epithelium and retina [4]. Although zinc deficiency was previously thought to impair retinol dehydrogenase activity, it is now known that this enzyme is zinc independent [7]. However, numerous other enzymes important in the visual cycle may be zinc dependent. Zinc deficiency can depress the hepatic synthesis of retinol-binding protein (RBP) and lead to lower concentrations of RBP in the plasma, which is required for mobilization of retinol from the liver [8]. In addition, there may be a specific role of zinc in the conversion of β-carotene to retinol via the enzyme 15-15 dioxygenase [9].

Zinc deficiency has been implicated in rod dysfunction and a patient with liver cirrhosis and night blindness was reported to show an improvement in rod ERG's after treatment with oral cholagogues, and this was attributed to recovery of deficient serum zinc levels and liver function [10]. Morrison et al. demonstrated a rapid recovery in cirrhotic patients with impaired dark adaptation and low serum zinc levels on zinc supplementation alone [11]. There appears to be an interaction between zinc and vitamin A in patients suffering from various pathological conditions that severely compromise hepatic function, such as alcoholic cirrhosis, CF and idiopathic haemochromatosis [8]. In humans, cross-sectional studies have more often than not shown a weak linkage between vitamin A and zinc status [8]. However randomized trials have failed to show a consistent effect of zinc supplementation on vitamin A status [8]. Circulating zinc and vitamin A levels appear unrelated in well-nourished states, but tend to co-vary in marginally nourished individuals, with co-existing zinc and vitamin A deficiencies [8]. Intestinal vitamin A malabsorption may be due to specific effects of zinc deficiency beyond any generalized effects of malnutrition. Thus zinc deficiency may result in a secondary vitamin A deficiency that is reflected in low serum vitamin A concentrations [7]. Conversely, severe vitamin A deficiency may reduce absorption and lymphatic transport of zinc by altering the synthesis of zinc-dependent binding protein [8].

Low serum vitamin A levels occur frequently in clinically stable, retinol-supplemented CF patients [12]. However due to the absence of a statistical correlation between hepatic and plasma levels of retinol in CF, serum retinol does not reflect vitamin A status [12]. A defective mobilization of vitamin A from liver storage tissues has been proposed as the reason for this, which indeed may be due to a co-existing zinc deficiency. Thus even in the presence of adequate hepatic vitamin A reserves, night blindness may occur when zinc deficiency exists [7]. However, to date, studies regarding zinc-related vitamin A deficiency in CF have been inconclusive [8].

A proportion of CF patients on oral vitamin A supplementation have abnormal dark adaptation and conjunctival xerosis due to vitamin A deficiency [13]. Some patients with abnormal dark adaptation do not respond to increasing their vitamin A intake until zinc supplements are administered [13]. In CF patients with vitamin A deficiency, therapy can be commenced with intramuscular water soluble vitamin A 30 000 IU [14]. However in this case it was difficult to source locally. Furthermore, high-dose vitamin A supplementation should be given with caution due to its potential for hepatotoxicity and risk of intracranial hypertension [12]. It was previously thought that among zinc deficient subjects, zinc on its own may not resolve night blindness or poor dark adaptation, but acts only to potentiate vitamin A in preventing night blindness [7]. This is the first report of a supplemented CF patient presenting with clinical vitamin A deficiency to be successfully treated with zinc supplementation alone.

Therefore in addition to retinol supplementation, normalising serum zinc levels may be important in maintaining the vitamin A status of CF patients. A routine enquiry as to whether patients were experiencing problems seeing at night would seem worthwhile. The European consensus on nutrition in patients with CF recommends up to 10 000 IU daily of fat soluble vitamin A, to maintain serum concentrations within the normal range. If serum concentrations are found to be low, despite supplementation to these levels, consideration should be given to patient compliance and zinc levels should be measured [15].