The interrelationship of thyroid hormones with vitamin A and zinc nutritional status in patients with chronic hepatic and gastrointestinal disorders.

To define the role of vitamin A, retinol binding protein, and zinc deficiency in producing the thyroid hormone abnormalities found in chronic illness, we studied 62 clinically stable patients with hepatic and gastrointestinal disorders. Serum triiodothyronine (T3) and free T3 index (FT3I) were depressed compared to controls (p less than 0.05) in the patients. Retinol binding protein and prealbumin levels correlated with both T3 and FT3I (p less than 0.01), whereas vitamin A levels did not. Vitamin A therapy in patients with documented vitamin A deficiency produced an increase in T3, thyroxine (T4), FT3I, FT4I, and free T3 by dialysis, with a concomitant increase in retinol binding protein and no alteration in prealbumin concentrations. Zinc-deficient patients had significantly depressed T3 and FT3I (p less than 0.001) and increased prolactin levels (p less than 0.01). Zinc supplementation failed to return any of these parameters to normal. Vitamin A therapy in normals produced a transient decrease in T3 and T4 after 1 wk of therapy, but after a further 2 wk, thyroid function returned to normal. Our data suggest a causal relationship between the pathogenesis of deranged vitamin A-retinol binding protein metabolism and the low T3 syndrome either by interfering with T4 entry into tissues or by directly affecting the enzymatic conversion of T4 to T3.

Acute ethanol administration causes transient impairment of blue-yellow color vision.

The higher incidence of blue-yellow color blindness (tritanopia) found among alcoholics could be due to genetic or acquired factors. The acute administration of ethanol to alcoholics and normal subjects transiently resulted in poorer color discrimination in all spectra but with significantly more errors in the blue-yellow versus the red-green color range (p < 0.005, p < 0.01). Thus, ethanol appears to act as a toxin to inner retinal layers, which could account for the higher incidence of tritanopia found among alcoholics.

Correlation of dark adaptation test results with serum vitamin A levels in diseased adults.

Dark adaptation, is a reliable and highly reproducible indicator of vitamin A nutritional status in terms of function. Abnormal dark adaptation occurs over a fairly wide range of serum vitamin A values; however, the lower limit of serum vitamin A which is related to normal ocular function has not been determined. We studied dark adaptation in 67 patients with a variety of hepatic and gastrointestinal diseases or with chronic alcoholism. We found that a serum vitamin A level greater than or equal to 40 micrograms % predicted normal dark adaptation 95% of the time, a serum vitamin A level greater than or equal to 30 micrograms predicted normal retinal function 68% of the time and a level greater than or equal to 20 micrograms % predicted normal function 27% of the time. Thus, in individual patients with serum vitamin A levels less than 40 micrograms % one can be sure of vitamin A sufficiency only if a normal dark adaptation response is elicited.

Vitamin-A reversal of abnormal dark adaptation in cirrhosis. Study of effects on the plasma retinol transport system.

Of 26 patients hospitalized with mild to moderate alcohol-associated cirrhosis, 14 had dark-adaptation abnormalities consistent with marginal vitamin-A status. The response of dark adaptation and the plasma retinol transport proteins, retinol-binding protein and prealbumin, was studied in 12 of these patients after daily oral vitamin-A supplements of 3300 microgram. Vitamin-A supplementation was associated with significant (p less than 0.05-0.005) improvement in dark adaptation and increased plasma concentrations of retinyl esters, retinol, and retinol-binding protein. Thus in patients with cirrhosis and marginal vitamin-A status, supplemental vitamin-A therapy appears to stimulate retinol-binding protein release from the liver. This enhancement of plasma retinol transport and delivery of retinol to peripheral tissues such as the retina is one of several factors that may serve to optimize vitamin-A nutritional status in patients with cirrhosis.

Zinc deficiency: a cause of abnormal dark adaptation in cirrhotics.

Six stable alcoholic cirrhotics with serum zinc less than 70 microgram/100 ml had abnormal dark adaptation responses (mean dark adapted final threshold 3.2 +/- 0.6 versus 2.1 +/- 0.2 log lux in 21 age matched controls, P less than 0.01). Serum vitamin A ranged from 15 to 37 microgram/100 ml. Zinc sulfate (220 mg/day) was fed to three patients for 1 to 2 weeks and dark adapted final thresholds fell 0.9, 0.4, and 1.2 log lux without concurrent rises in serum vitamin A. Two patients were treated initially with oral vitamin A (10,000 IU/day) for 2 to 4 weeks, but their final thresholds fell to normal (2.1, 2.2 log lux) only after the addition of zinc for 1 to 2 weeks. The sixth patient, treated with vitamin A and zinc together, attained a normal final threshold in 2 weeks. The improvement in dark adaptation by zinc may be due to enhanced activity of previously depressed retinol dehydrogenase.