Their methodology, which “essentially matched retinol levels with variation in genes”, could be used to inform future approaches for a variety of health conditions, from brain disorders to autoimmune diseases, to chronic obstructive pulmonary disease (COPD) and asthma.
Professor Murray Cairns, from the University of Newcastle and Hunter Medical Research Institute, told Vitafoods Insights: “We used the genetics of retinol to derive a genetic risk score that could be used to target some individuals for these interventions (diet/supplement/synthetic) that are more likely to have low circulating levels.
“This is a genetically informed precision health/medicine approach that could be a game-changer for the way we think about diet and supplements.”
Vitamin A ‘hugely important’ for brain, immune, skin, and vision health
Vitamin A – a fat-soluble nutrient that is abundant in meat, along with green and orange plants – plays a crucial role in many biological processes throughout the human lifespan. Retinoid acid, the bioactive metabolite of vitamin A, is a potent signalling molecule in the brain.
The connectivity between neurons in the brain is thought to be altered in people with schizophrenia and other psychiatric conditions. Previous research has suggested that this may be related to vitamin A – or retinol – levels, which are known to play an important role in the differentiation, maturation, and synaptic function of brain cells.
“Retinol is hugely important for many aspects of our development: brain, immune system, skin, and vision. It’s really important to know what it does and how it can be used more effectively to improve human health,” Cairns said.
For the latest study, which was published in Nature Communications, the researchers combined statistics from thousands of individual genomes to identify which genetic factors regulate retinol levels in blood, enabling the team to better understand its role in several complex health conditions.
The genetic variants associated with retinol “can be utilised to understand potential causal relationships with human health and disease”, the study authors argue.
Cairns added: “While we have previously focused on the role of retinoid genetics in schizophrenia, the current study is much broader because we investigated the genetic basis of circulating retinol. We were then able to use this a genetic proxy of the circulating levels in nearly 20,000 traits using causal inference.
“This approach is much more reliable than observational studies, which are frequently underpowered, and confounded by correlation and reverse causation. We need to know the causal role of these molecules in a given condition to enable them to be used effectively in prevention and treatment.
“We also need to know how this is affected by genetic heterogeneity and target people that will benefit more specifically based on their individual disposition.”
Retinol supplementation: Implications for industry
Currently, retinol supplementation is not indicated apart from in the case of deficiency, which is rare in high-income countries. Previous studies have explored the effects of supplementation, a high vitamin A diet, and/or measured circulating retinol in a variety of disease contexts; however, findings have been inconclusive.
Asked about the implications of the recent research for industry, Cairns told Vitafoods Insights: “Our study clearly highlights the significance of vitamin A to a variety of health condition[s]. In some cases, supplementation with the vitamin or dietary derivatives or synthetic analogues will be helpful for some individuals that may be in deficit or have a genetic disposition for low circulating levels.
“Rather than target any group of individuals based on their presentation with disease, we would suggest that it might be more valuable to target supplementation or pharmaceutical intervention to people based on their genetic disposition for low circulating retinol.”
Asked about the direction of future research, he added: “The next step in our research programme will be to test this approach rather than target people in general for supplementation.
“This is also important given that too much vitamin A can also be a problem, particularly in pregnant women, as foetal development can be adversely affected by extra-physiological levels of the vitamin. Vitamin A is particularly potent and should only supplemented under the supervision of a clinician.”
