Relationship between fatty-liver disease and vitamin A-retinol needs more research, experts flag

14 Sep 2022 --- A recent review of the existing scientific literature has found that the link between non-alcoholic fatty liver disease (NAFLD) and vitamin A, or retinol, is contradictory at best and warrants further scientific investigation. The mechanism involved includes retinol-binding protein 4 (RBP4), which transports retinol from the liver to other organs.

NAFLD is a potentially chronic and serious disease that affects an estimated 25% of adults globally. Patients suffering from NAFLD have a 33% greater chance of developing coronary heart disease, and it is linked to numerous other diseases, including cancer. 

“In recent years, the prevalence of NAFLD-associated hepatocellular carcinoma has shown an increasing trend in many countries,” says Dr. Chengfu Xu, co-author of the paper. “The proportion of hepatocellular carcinoma attributed to NAFLD tripled from 3.8% in 2001–2005 to 12.2% in 2006–2010 in Korea.”

“Similarly, this proportion increased from 2.6% in 1995–1999 to 19.5% in 2010–2014 in France,” he continues. “Therefore, NAFLD poses a substantial burden on global health resources and the economy.”

A wealth of contradictionsThe researchers hold that more work must be done to discover the link between NAFLD and retinol.
The study, published in the Chinese Medical Journal, states that though many studies have found a link between RBP4 and NAFLD, there are “several obvious contradictions.” Case in point, a Turkish study recently reported finding higher levels of RBP4 in obese children with NAFLD. However, an Italian study found a negative correlation between the two factors in children with NAFLD.

“These contradictory findings may result from the heterogeneity of fatty liver detection methods and study participant’s race, as well as the limited size of the study sample,” explains Xu. “The studies observed no significant association or an inverse association between RBP4 level and NAFLD.”

“It is worth noting that none of these studies found a significant correlation between serum RBP4 level and body mass index, waist circumference, and fasting plasma glucose or insulin levels, although the correlation has been confirmed in a large body of studies.”

Tracking the culpritNAFLD affects over 25% of adults globally.
Since vitamin A has been found to have numerous health benefits, like preventing blindness and decreasing childhood mortality rates, proving whether or not it is negatively associated with the development of NAFLD is highly important. 

The study has shed light on some of the potential mechanisms involving NAFLD. One such instance reveals that RBP4, which is stored mainly in the liver, is easily filtered by the kidneys. However, a thyroid hormone carrier called transthyretin (TTR) prevents filtration. 

Furthermore, the researchers found that the therapeutic fenretinide decoupled RBP4 from TTR, prompted fatty oxidation in the liver, improved glucose tolerance and inhibited NAFLD development by promoting renal excretion of the protein and lowering RBP4 levels. 

The researchers hold that these findings should help future studies find whether retinol and its corresponding transport protein are indeed linked to the incidence of NAFLD as well as revealing what may be done about it.

“These findings raise the possibility of targeting RBP4 as a novel marker and a potential therapeutic target for NAFLD,” Xu concludes.  

Edited by William Bradford Nichols