Liver disease may cause vitamin D deficiency. The liver is responsible for converting your vitamin D into circulating form 25(OH)D. There are a few different explanations why liver disease may cause vitamin D deficiency.
In cholestatic liver diseases, conditions where bile flow cannot flow from the liver to the duodenum, cholestasis reduces the intestinal availability of bile salts needed for the absorption of fat-soluble vitamins. It also affects the conversion of vitamin D to 25(OH)D. Furthermore, parenchymal liver disease may cause abnormalities of vitamin D metabolism, also causing vitamin D deficiency.
In a new study published in the Annals of Epidemiology, researchers wondered, since liver disease causes vitamin D deficiency, and liver disease is also associated with all-cause mortality, might liver disease explain the association between vitamin D deficiency and all-cause mortality? In other words, is vitamin D just a byproduct of the association between liver disease and all-cause mortality, having nothing to do with all-cause mortality itself?
To study this theory, the researchers looked at the MONICA 1 study cohort, a Danish cohort that enrolled 3,785 persons between 1982 and 1984. Of these persons, a total of 2,649 persons were followed up with 10 years later, in 1993 and 1994. In 1982-1984, the researchers measured vitamin D levels, serum alanine aminotransferase, aspartate aminotransferase, and gamma glutamyl transferase, the latter three used as markers for liver disease.
The researchers then used the Danish Central Personal Register to follow the 2,649 persons from 1993 and 1994 for 17 more years. Of these persons, there were 736 deaths.
Did liver disease explain the association between vitamin D deficiency and all-cause mortality? Here’s what they found:
- In general, at baseline, high markers of liver disease were significantly associated with lower vitamin D status.
- In raw data, people in the upper quartile of vitamin D had a reduced risk of all-cause mortality over the 17 years compared to those in lower quartiles.
- When the researchers adjusted for liver disease markers, their data did not change the above association. In other words, liver disease did not explain the association of low vitamin D and increased risk of death.
The researchers concluded,
“Contrary to our expectations, the inverse association between vitamin D status and all-cause mortality was not explained by liver damage. Thus, taking levels of liver enzymes into account did not attenuate the estimates of the association between 25(OH)D and mortality risk.”
To date, observational studies examining a relationship between vitamin D and all-cause mortality have fairly consistently found that low vitamin D is associated with higher all-cause mortality. This study rules out liver disease as a potential confounder.
However, we still need further research to understand if the relationship between low vitamin D and death is causal. Meta-analyses of randomized controlled trials suggest that it probably is, but bigger population studies are still needed.