Averting Autism - Antenatal Antioxidants? But Male, Female or Both?

 

 Salem College

 

Today’s post is the first of two new ones about preventing/minimizing future autism.  The second post will be about Dr Ramaekers’ idea of using Calcium Folinate, which he has already put into use in human parents seeking to avoid autism in their next child. 

Before we start, I should point out that while readers of this blog, and it seems Dr Ramaekers, likely wish that autism and its symptoms did not exist, there are some people, well paid to research autism, who think autism is a good thing. I really do wonder why such people receive any public funding and wonder what kind of University would employ such people. It is like researching deafness, but not wanting to treat it - better they stay home.

https://www.sciencedaily.com/releases/2020/08/200824091958.htm

Simon Baron-Cohen, PhD, Director of the Autism Research Centre at Cambridge, who co-led the study, added, "Some people may be worried that basic research into differences in the autistic and typical brain prenatally may be intended to 'prevent,' 'eradicate,' or 'cure' autism. This is not our motivation, and we are outspoken in our values in standing up against eugenics and in valuing neurodiversity. Such studies will lead to a better understanding of brain development in both autistic and typical individuals."

Even more odd is that Baron-Cohen's sister had a rare mutation of the GNAQ gene that led to intellectual disability and a reduced lifespan. Why would you not want to treat/prevent that?  Treating your sister would not have meant you did not value her, it would have been another sign that you loved her. 

A positive example is another autism researcher, Manuel Casanova, and his family, who set up a research effort for people who have a disorder related to the gene NGLY1.  Sadly, Manuel's grandson passed away, but the research goes on.   

If you can escape from intellectual disability, someone should make it happen.  That someone might be you.

 

I must admit I had never heard of Salem College.  It is an all-female college in Winston-Salem, North Carolina.  It is the source of another idea to avert autism, this time treating the future father with an anti-oxidant like NAC.  NAC was already on my list for future mothers.  When it comes to autism, it looks like little Salem College is going to be more useful than stuffy old Cambridge University.

I am rather surprised there still are all female colleges, but in the US, there are many.

My mother went to an all-female college at Cambridge University, back then they had no mixed colleges.  Only after 1948 could women even receive a degree at the end of their studies. Cambridge University still has three all-female colleges.

Clearly male post-conception antioxidant supplementation is not going to help.

We have already seen in the research that the future father can damage the DNA he passes on to his offspring.  This was done via epigenetic tags on his DNA caused by things like recreational drug use, or smoking tobacco.

The author of today’s paper look’s exclusively at autism risk from the father, but exactly the same therapy during pregnancy can reduce risk from the mother.  The maternal immune activation model is one of the most studied in autism. We also know that emotional stress during pregnancy increases autism risk.  Emotional stress leads to oxidative stress.

The only issue I had with this preventative approach is whether there are any negative effects from antioxidants during pregnancy.  There may well be none, since the body just adjusts production of its own antioxidants.

There was an interesting experiment I mentioned a while back about giving antioxidant or “detox” juices to healthy young people.  The anti-oxidants from the fruits just made the body reduce its own production of GSH/glutathione, so the net result of the detox juice was actually negative.  People in oxidative stress benefit from anti-oxidant therapy, everyone else is wasting their money.

There are highly conflicting reports as to whether autism tends to come from the mother’s half of the child’s DNA or from the father’s half.  In reality it does not matter, it can from either, both or neither.  What is important is to take whatever simple safe steps you can to avert future autism. 

Future parents taking NAC and Calcium Folinate, might as well join the idea of keeping pets at home during pregnancy to get exposure to the evolutionarily expected bacteria that are needed to calibrate the immune system of the fetus/baby. Humans have been living with dogs, and very importantly their bacteria, for 11,000 years.  Only very recently did humans come up with the idea of trying to kill 99.9% of bacteria in their homes. 

Dogs are humans' oldest companions, DNA shows

I really do not see anyone doing a placebo controlled clinical trial on any of this.  Nobody who agrees to participate will accept the risk of being in the placebo group.  You would have to create a control group out of people who did not want to join the trial.  The people who join the trial are self-selected and are more likely to be health conscious, or have a family history of autism or dys-something else.

Male preconception antioxidant supplementation may lower autism risk: a call for studies

Current research indicates that a sizable number of autism spectrum disorder (ASD) cases arise from de novo mutations (DNMs) occurring within the paternal germline, usually in an age-dependent manner. Andrologists have reported that somatic cells and gametes share the same pathologies that generate these DNMs—specifically, DNA hypomethylation caused by oxidative nucleoside base damage. Because many ASD researchers seek to identify genetic risk factors, teams are developing methods of assessing aberrant DNA patterns, such as parental gonadal mosaicism. Several studies propose antioxidant supplementation as a strategy to lower autism risk, and/or suggest connections between childhood neurodevelopmental disorders such as autism and paternally-derived DNMs. Actual data, however, are currently not available to determine whether male preconception antioxidant supplementation effectively lowers autism risk. The purpose of this paper is to (1) explore the mechanisms causing DNMs, specifically DNA hypomethylation; (2) explain how antioxidant supplementation may lower the risk of having a child with ASD; and, (3) advocate for the implementation of large prospective studies testing (2). These studies may very well find that male preconception supplementation with antioxidants prevents neurodevelopmental disorders in offspring, in much the same way that female prenatal consumption of folate was found to decrease the risk of birth defects. If this is indeed the case, the alarming rise in autism prevalence rates of the past few decades will slow—or even cease—upon the initiation of public awareness campaigns.

  

Antenatal antioxidants to avert autism?

Paternally derived de novo mutations (DNMs) caused by oxidative stress (OS) have been implicated in the development of autism spectrum disorders (ASDs). Whether preconception antioxidant supplementation can reduce the incidence of ASDs by reducing OS is an area of uncertainty and potentially important future scientific investigation.

The recently completed double blind, multicenter, randomized controlled Males, Antioxidants, and Infertility (MOXI) trial by the Reproductive Medicine Network (RMN), funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), investigated whether antioxidants improve male fertility, as measured by semen parameters and sperm DNA integrity at 3 months and pregnancy by 6 months of treatment [11]. The RMN investigators found that antioxidant treatment of the male partner does not improve semen parameters, sperm DNA integrity, or in vivo pregnancy rates in couples with male factor infertility, prompting the question whether antioxidant therapy should no longer be routinely recommended for infertile men [12]. It would be intriguing to evaluate the offspring from the participant couples of the MOXI trial for ASD. However, with only 13 live births in the antioxidant group and 21 live births in the placebo arm, the study would be vastly underpowered to demonstrate a benefit of antioxidants in the prevention of a condition with an incidence of 1 in 54 children.

The next post is about Dr Ramaeker's clinical trial of calcium folinate in children with autism and his comments about their parents and future siblings.