Vitamin D and Autism: New Research by Dr. Bruce Ames
So you know occasionally something gets reported in the literature that just peaks our interest, and creates an “ah-ha” experience, and fills a gap in our knowledge. Such is this paper I’m holding in my hands by our very…I think I would call him a friend of our family for years in the nutrition area and the Institute for Functional Medicine, and that’s Dr. Bruce Ames, Professor Emeritus from the University of California, Berkeley—ex-chairman of the biochemistry department there and more recently at the Children’s Oakland Research Institute in Oakland, California.
The title of this paper is, I think, quite remarkable, because it ties together so many different loose ends. Let me just cite the paper title and then you can see what neurons it turns on for you:
Patrick RP, Ames BN. Vitamin D hormone regulates serotonin synthesis. Part I: relevance for autism. FASEB J. 2014 Feb 20.
Oh boy, that’s quite a title, isn’t it? So let’s go back a moment. Not too many moments ago—maybe 15 or 20 years ago, or less—in which if I was to say “Vitamin D: 1,25-dihydroxycholecalciferol and its metabolites,” what would you identify with? You would identify with rickets, right? Because we all know that vitamin D is the nutrient required to prevent this children’s disease of the bones—deformity of the bones, the skeleton—that we call rickets. And then later, you would think, well, it’s also good for older-age women and osteoporosis prevention. And then you might go on to say, “But more recently we’re finding that it has all sorts of pleiotropic effects,” meaning multiple effects across multiple organs and multiple conditions.
How can one compound—1,25-dihydroxycholecalciferol—have all these myriad different effects? Well, the answer is not snake oil. The answer is that it has been found that vitamin D has a very important role to play as a nuclear orphan receptor agonist. Whoa, there’s a long term. What does that mean? What it means is that it speaks through the nuclear envelope of the nucleus of cells that, as you know, is the center of where the genome is encoded and captured and protected from the rest of the cell. It speaks to that genome through its ability to serve as a transcription factor, and that means it upregulates or modifies the expression of specific cassettes of genes that are associated with different functions, and different cells, and different tissues of different organs. It has, then, a pleiotropic effect.
Well, that’s a pretty remarkable kind of new insight as to the role of vitamin D, and one of the first early signs of vitamin D inadequacy has been historically and anecdotally said to be none other than dysphoria. Now what is dysphoria? Dysphoria is an early stage of what we later call depression. So mood disorders are associated with vitamin D inadequacy—chronic inadequacy, not acute inadequacy that you see with osteoporosis or rickets, but chronic inadequacy.
But how does that work? Well, now, says this article, it is now recognized that one of the pleiotropic effects of vitamin D is its regulation of the expression of various hormones that are associated with mood, such as serotonin itself. In fact, not just that of serotonin, but hormones that relate to all sorts of endocrine effects, like oxytocin, for instance, and vasopressin, which as you know has to do with memory. So we’re talking about a neuronal effect of vitamin D that is far beyond that of its bone protection effects.
Now this is a very, very interesting observation because when then woven through the lens of Dr. Ames and his colleague, the co-author Dr. Patrick, of this paper that appeared in the Federation of the Society of Experimental Biology journal in 2014, it comes to pass that they recognize that many of these pathways that are associated with some of the neurological issues that are seen in children with autistic spectrum disorders and autism. So the proposal is, from this work, that this may be another one of manifest outcomes of suboptimal vitamin D status, particularly vitamin D status of the nervous system, and that is alteration of these neurochemicals that is associated with affective behavior disorders and situations that might be called autistic spectrum disorders.
Now, does that mean that all forms of autism are caused by vitamin D insufficiency? Of course not. This is just another in the myriad of interesting factors that are associated with genetic susceptibility to the structural outcome that we call autism.
Now as you go through this particular discussion in the Ames paper, what you will find is he talks a lot about the activity of vitamin D and the expression of an enzyme called tryptophan hydrolase. This particular enzyme, this hydrolase enzyme (hydroxylase 2 of tryptophan) is involved with the downstream metabolism of tryptophan into things like serotonin, as an end product, and going into the kynurenic pathway. So this concept of neurochemical regulation and vitamin D is now emerging as a very interesting additional part of the chapter of this title.
Now, if you would take this to an explanatory level, you might want to take a look at a blog on our website by Dr. Ben Brown. Dr. Brown has done a really nice job of reviewing the paper of Dr. Patrick and Dr. Ames, and looking at how this concept of suboptimal vitamin D connects into the appearance of the diagnosis of autistic spectrum disorder.
Again I want to emphasize we’re not saying that all ASD or autism comes from a vitamin D deficiency. We just want to add this to the list of variables that participate, ultimately, in the manifestation of an altered neurochemical pathway, behavior, function that ultimately we call autism.
I think this is a very, very powerful part of the expanded frontier of how we’re starting to look at nutrients, particularly these nutrients like vitamin D, and vitamin A as well, which, as you know, is converted into retinoic acid, because retinoic acid is another nuclear orphan receptor agonist that can participate in gene effects and gene expression modulation. So when we start examining these roles, it’s much more than just the prevention of a vitamin deficiency, like xerophthalmia prevention with vitamin A or rickets prevention with vitamin D. We’re looking at a panoply or a variety of different gene response that really relates to genetic uniqueness of the individual. And in this case, I think the connection between autistic spectrum-like disorder and suboptimal vitamin D and dysphoria and depression is starting to gain some traction based upon mechanistic insights.
I hope this is somewhat interesting to you, and again I urge you to take a look at our blog from Dr. Ben Brown on the website. I think you will find it very interesting news to use.