I am a registered dietitian who works with adults with Autism, but I happen to be the mother to an amazing Zoey. She struggles with oxalate. Over the past 9 years I thought I was maintaining her low oxalate diet, but a bad handout from another registered dietitian that is trusted in the kidney disease community online resulted in me basically poisoning my daughter with plantain. She was only getting a little plantain every now and again for many years. Looking back on this situation, it worsened in 2021. when I switched out some of her flour in my low oxalate bread recipe with plantain flour. It culminated in severe oxalate poisoning in January of this year when I used only plantain flour to make banana muffins. She ended up in the ER due to severe vomiting. The doctors couldn’t figure out what was wrong and told me she had some unknown virus. After they left they released all the results to her MyChart. I saw that she had high amounts of amorphous crystals in her urine and bladder debris. The only change I had made was the plantain flour increase.
Some good has come from that poisoning because I realized that plantain flour is NOT low in oxalate, but more importantly I made a huge discovery. I asked for metabolic lab work to be done and the results forced me to explore a connection between Zoey’s increasing serum retinol levels and her dietary intake of oxalate. As her dietary intake of plantain flour increased, her serum vitamin A increased.
I would also like to say my clients with neurological issues are having similar symptoms as Zoey. I, of course, can’t share their stories here, but they all are impairing Vitamin A metabolism in different ways (Miralax, high Vitamin A tube feedings, High Vitamin A supplement paired with famotidine, Iron deficiency and high dietary oxalate).
This isn’t an isolated occurrence, and if you search vitamin A in the TLO group (trying low oxalate group) it is a recurring theme there as well. In fact, I think that many of the skin issues that this group calls “dumping” are actually localized increases in retinoic acid production due to decreased oxalate levels in cells. When vitamin A metabolism moves forward to retinoic acid, they see skin peeling off and hair falling out because new skin and hair are finally being made in the correct way instead of excessive keratin production.
Now on to my hypothesis.
Hypothesis:Oxalate can impair vitamin A metabolism which results in high retinal levels and complexing of retinal with ethanolamine which lowers this important ether lipid in the nervous system resulting in neurological sequelae of autism.
Mechanism: Zoey, my 11 year old daughter, has hyperoxaluria of some kind (waiting to get into metabolic genetics to see if it is genetic in origin, but as you know dietary oxalate also must be reduced in cases of familial hyperoxaluria). She has elevated ALT, keratin accumulation in the skin, headaches, fatigue, increased histamine reactions, history of kidney stones, fatigue, poor wound healing, and failure to grow. She also has diffuse cerebral dysfunction with epileptic discharges, gross and fine motor delay, impaired speech, ataxia, and dysphagia.
I requested plasma amino acid, urinary organic acid, pyruvate, lactate, and vitamin A levels checked due to her severe fatigue and the problems above. Her vitamin A levels have been creeping up for the past two years and are at toxic levels now (toxic on quest lab at 71). Her lactate is severely low. Her ethanolamine is very low.
When the body is producing lactate, it also produces NAD+ which is what drives retinol metabolism forward. While looking at ways to help her itching skin, someone in a support group mentioned that lactic acid lotion helps with keratin accumulation. Then, my mind exploded and I went on a deep dive into literature. What I found is that Oxalate doesn’t directly inhibit alcohol dehydrogenase or retinol dehydrogenase or aldehyde dehydrogenase which was what I was searching for. Oxalate actually impairs lactate dehydrogenase (LDH). I hypothesize that oxalate takes away the “energy” needed to drive those reactions forward by impairing LDH. LDH is actually the last enzyme involved in the formation of oxalates. I believe that oxalate being able to have a feedback inhibition on LDH is a safety mechanism built into our human biology, but that it backfires and wreaks metabolic havoc on vitamin A metabolism and also energy metabolism.
So, essentially my 11 year old daughter is potentially toxic in retinol because she can’t convert vitamin A to retinoic acid. She has all the signs of vitamin A deficiency, but is actually toxic. I believe her retinal is also high, and in fact, that carotenoids have now become a problem for her due to these enter vitamin A metabolism at the level of retinaldehyde. I believe that retinal is “stealing” her ethanolamine by creating A2E in the nervous system. I hypothesize that this is the part of the cause of her Autism. She obviously has MBD5 deletion, but many of the kids in our support group are not as disabled as she is from a fine motor, gross motor, or verbal standpoint. These other kids have massive seizures but live life normally. So what if this is the difference? What if I can help her be “better” although she is amazing already.
I believe that gut microbiome as well as B6, Thiamine, and Niacin depletion are contributing factors to low NAD production resulting impaired vitamin A metabolism and excess retinal stealing ethanolamine. In fact, Zoey’s labs show high tryptophan, high lysine, and low urinary glutaric acid indicating that her secondary pathway of NAD production is severely compromised as well. I hypothesize that excessive urinary excretion of oxalate increases B6 losses and leads to down regulation of NAD production via Tryptophan and Lysine interrelated pathway.
However, as I described above, there is more than one way to screw up NAD/NADH balance in the body resulting in impaired Vitamin A metabolism.
Here is my ongoing research on vitamin A metabolism. I plan to chunk this into smaller blog posts and give more detail on each one. http://weakthereforestrong.com/impaired-vitamin-a-metabolism-retinoic-acid-deficiency-and-neurological-decline/?preview_id=398&preview_nonce=e78f88c779&preview=true
Here is my hypothesis that vitamin A metabolism and catabolism is all about ratios that I worked on with Jenny Jones, my molecular geneticist friend. https://weakthereforestrong.com/its-all-about-the-ratios-the-ratios-more-nad-nadph/
I would love to be part of a research study on the link between oxalate, vitamin A, ethanolamine, and Autism or any component involved in this crazy pathway that I have identified over the past two months. As a dietitian, I have a unique perspective on this issue and could be helpful in research and writing. Also, I will sign my daughter up for this research study as well, if we could help in any way, as long as it is a “safe” study. She has suffered miserably these last few years because of a well meaning dietitian’s error. I want Zoey’s suffering to have purpose.