28 Dec 2021

The DFEND Trial, published in JAMA Network Open, involved 149 participants with early psychosis, who were randomised to receive vitamin D or a placebo for six months.

The study was funded by the Stanley Medical Research Institute and received support from the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre, King’s College London and the NIHR Applied Research Collaboration (ARC) South London.

Insufficient vitamin D levels

While the study showed no evidence of vitamin D supplementation improving physical or mental health symptoms, it revealed 74.6 per cent of participants had insufficient or deficient vitamin D levels, with that figure rising to 93.4 per cent among ethnic minority participants.

Vitamin D deficiency is more common in people with psychosis than the general population. This is thought to result from poor general health associated with inactive lifestyles, less exposure to the sun and poor general nutrition. Animal experiments have linked low vitamin D with changes in the brain, triggering speculation that vitamin D supplementation could improve mental health.

No previous studies have examined vitamin D supplementation in people with first episode psychosis, a group with high rates of vitamin D deficiency (42 per cent) and who may be more responsive to supplementation than those with established psychosis.

Measuring long-term health impacts 

The study’s lead author Professor Fiona Gaughran, professor of physical health and clinical therapeutics at the Institute of Psychiatry, Psychology & Neuroscience, King’s College London, and consultant psychiatrist at the National Psychosis Unit at South London and Maudsley NHS Foundation Trust, said:

“While we didn’t show any effect of supplementing with vitamin D on mental or physical health over a six-month period in people with early psychosis, the rates of vitamin D insufficiency and deficiency in the group overall were very high, this state being almost universal in participants from Black or other minority racial or ethnic groups. Giving the vitamin D supplements increased vitamin D levels and was safe.

“These very high rates of vitamin deficiency and insufficiency may have longer-term negative health impacts which we have not measured, so raising awareness of the need to optimise vitamin D in people with psychosis is important. Future public health strategies should acknowledge the high risk of vitamin D insufficiency and deficiency in people with psychosis and consider any reasonable policy adjustments which may be needed to address this over and above general population guidance.”

Looking for new treatments

The study recruited participants aged 18 to 65 between 2016 and 2019 from five NHS trusts in England: South London and Maudsley NHS Foundation Trust, Southern Health NHS Foundation Trust, Cheshire and Wirral Partnership NHS Foundation Trust, Kent and Medway NHS and Social Care Partnership Trust and South West London and St George’s Mental Health NHS Trust.

Participants were randomised to receive 6ml of vitamin D or a placebo administered by researchers in monthly doses with an oral syringe each month. Both researchers and participants were not told which they would receive, to avoid bias.

The researchers assessed participants after three and six months to check for any changes in their psychosis symptoms, with mood, function and cardiometabolic risk factors also measured at six months.

Senior author on the study, Professor John McGrath of Queensland Brain Institute, University of Queensland, Brisbane, Australia, said:

“While animal studies indicate that low vitamin D during adulthood can alter brain functioning, the DFEND study did not find evidence that vitamin D supplementation helped people with early psychosis. This is disappointing, but we will continue to look for new candidate treatments for psychosis – this can be a very disabling illness and our current treatments are suboptimal.”

Find out more

The paper ‘Effect of Vitamin D Supplementation on Outcomes in People with Early Psychosis: The DFEND Randomised Clinical Trial’ was published in JAMA Network Open. doi:10.1001/jamanetworkopen.2021.40858