Could Vitamin D Be Leveraged as a Way to Treat Adrenoleukodystrophy?

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The assistant professor of neurology at Stanford University addressed the possibility that vitamin D’s role on cells within the human immune system could have a therapeutic influence in neuro-metabolic disorders such as ADL.

Dr Keith Van Haren

Keith Van Haren, MD, an assistant professor of neurology at Stanford University

Keith Van Haren, MD

Recent research into the role vitamin D plays in human immune cells in both healthy and diseased circumstances conducted by Keith Van Haren, MD, and colleagues, has suggested that the vitamin may have an effect on disorders of fatty acid metabolism, such as X‐linked adrenoleukodystrophy (ADL).1

Van Haren, an assistant professor of neurology at Stanford University who specializes in child neurology, and his colleagues in the Stanford laboratory are extensively interested in the implications of these findings. Van Haren told NeurologyLive that there is a possibility that vitamin D could be leveraged in some way to have a sort of therapeutic effect in these conditions.

The findings showed that vitamin D plays an unexpectedly prominent role in fuel dependency, energy efficiency, and cell survival within the human immune system. To find out more, NeurologyLive spoke with Van Haren in an interview.

NeurologyLive: Are there any clinical implications of these findings?

Keith Van Haren, MD: If we then begin to look back at vitamin D as something that facilitates energy synchrony, it has implications for, we think, lots of aspects of human biology. In fact, higher vitamin D states put our biology in a more energy-efficient state, so we waste less energy on heat. We can use that energy for other things, perhaps. Things like fighting off infections and illnesses, and in our case, we think there's a future story here around vitamin D's relevance to childhood brain development. That's the period of life when metabolic demand by the brain is at its peak. Brain metabolism peaks in the first decade of life, and there are some interesting clues—not from our data, necessarily, but from other published work—that may suggest that humans have really been leveraging, somewhat, different aspects of vitamin D biology for other reasons. It's possible that this is part of it, that basically vitamin D is something that regulates efficiency and glucose metabolism and fat metabolism. We see logic as to how it might be leveraged by a biohack, by human evolution and primate evolution, to generate more energy in the organism and more energy, potentially, for something as expensive as the brain.

Are there any plans to look into this further in future studies?

Oh yes, plenty, but getting funding for those plans is another story. But the data that we have are huge datasets from these transcriptome work, so there's a lot more in there to carve out. We think there are some clues here as to potential differences between, for example, an MS transcriptome and a non-MS transcriptome that may provide insight into some unknown, unmapped features of MS biology, perhaps.

But for our lab, which is interested in ALD and childhood disorders, and to some degree MS, this is particularly relevant to some of the neuro-metabolic disorders we study. If this is regulating energy efficiency, potentially, for the immune system—so might it for the brain, so might it for normally developing human brains.

For kids of any age, but particularly kids with neuro-metabolic disorders, any marginal effect of an energy efficiency gain could really valuable, and that is what we're perhaps seeing in our v ALD experience. Vitamin D actually may be just moving the needle enough to keep some of the more of these boys with ALD from developing some kind of metabolic failure and inflammation. For people who kind of ride that knife edge through childhood of having just enough energy to make the margin call for whatever the day’s brain or metabolic demands might be, enough vitamin D may be enough to make a difference. It's clear that it's not the be-all end-all metabolism or neuro-metabolism or immunometabolism, but maybe we will be able to pull one of those levers in the future.

REFERENCE

1. Van Haren K. Monocyte, T‐cell, and B‐cell Transcriptomes from Multiple Sclerosis Patients Treated with Vitamin D Highlight Metabolic Pathways Relevant to Immune Regulation. Presented at: Child Neurology Society annual meeting: Chicago, IL; October 15 to 18, 2018. childneurologysociety.org/docs/default-source/2018-cns/platform-presentations-2018.pdf.

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