Sunday, January 22, 2012

Autism and Antioxidants -- A Wee Little Explanation

To start off, here is Elvis Presley's last Number 1 hit:  A Little Less Conversation (right click to open in new tab)

Yesterday I put up a little post discussing a very theoretical possible link between acetaminophen and autism.  The main point is that acetaminophen is known to gobble up glutathione like gangbusters, and some of us will be more vulnerable to this glutathione destruction than others.

Glutathione is a major part of the body's detoxifying systems.  When we burn fuel and various other biochemical things, we create toxic byproducts.  These toxins can damage DNA and make systems inefficient and ragged, and call up our inflammatory army to clear the damage, which can cause its own problems.  Since our body is a tiny little ecosystem, we have our own chemical clean-up crew that should be johnny on the spot to sop up free radicals and other untoward elements.  We can measure how good our clean-up crew is in various ways, and a couple of very small studies have demonstrated that kids with autism don't seem to be very good at dispensing with toxins.  In this Egyptian paper (1), kids with autism have lower rates of superoxide dismutase and glutathione peroxidase than matched control children (this could mean they make less or are dealing with more oxidation than other kids, so the enzymes are used up faster).  These two enzymes clean up superoxide and the resultant hydrogen peroxide, reducing them to less dangerous downstream products. I have also reviewed a study showing inefficient and dirty mitochondria in children with autism compared to controls.

A free radical courtesy Flickr Creative Commons

Children under 3 not only grow at a rapid rate, they also seem to have naturally low glutathione levels, making them among those particularly vulnerable to oxidant injury (2).  Children who have genetic inefficiency in the antioxidant system will therefore be even more vulnerable.  The brain, being a high energy and relatively delicate organ (the liver has an astonishing capacity to regenerate cells, whereas the brain has almost no capacity to regrow cells but can modulate connections to bypass injured systems to some extent) will be especially susceptible to oxidative damage.  Another area vulnerable to lack of glutathione?  Our delicate airways -- one of the reasons perhaps some children eventually "grow out" of asthma.

Guess what else is exceedingly important in establishing an amazing and efficient antioxidant system?  That's right.  Micronutrient status.  Copper and zinc need to be topped up in order to make plenty of superoxide dismutase, for example.

You know who else tends to have a less efficient antioxidant-making system and lower amounts of glutathione?  Yes, the elderly.  As I've mentioned in the past, the pathophysiology of autism and dementia seem to have some similarities -- a similar puzzling and devastating process of inflammation and neuronal cell death occurring at entirely different developmental stages.

These are all complex processes with many players, internal and external.  That's why I don't think there is any "one" cause of the autism spectrum disorders (or the dementias, for that matter).  However, combine a genetic vulnerability, low zinc status, maybe some acetaminophen, and inflammatory insult, and ultimately there is a straw that breaks the camel's back.

The good news is that most of us are resilient and can handle a bit of acetaminophen here and a bit of red #5 there, and some of us sail through life smoking cigarettes and chomping on funky fries.  The bad news is that some of us aren't as resilient, and one way or another we will all have to pay the piper.


  1. I love the glutathine talk, it's non-polarizing. We don't have to be all like "Rawrg shut up, glutathione supporters, you don't know what you're talking about blah blah blah" because everyone is on board with glutathione being a good thing. Group hug!

    For anyone wanting to boost their glutathione status, sulfur (and therefore eggs!) is a rate-limiting factor for its synthesis So is protein according to Chris Masterjohn.


  2. Me again (sorry, it's late here and this is the last comment of the day!).

    Glutathione and autism = very interesting area.

    This study by Al-Yafee and colleagues (open-access) : suggested that despite the small sample sizes included for study, there was an AUC=1 (area under the curve) with regards to total glutathione levels. Even the highest value of the children with autism was below the lowest of the control group. Needs replication, needs larger participants numbers, needs lots and lots more study. (But still is a very interesting finding).

    'Nuff said.

  3. As I recall, the link between maternal acetaminophen use during pregnancy and children's asthma has recently been shown to be quite strong, so that is reason enough to stay away from the acetaminophen.

  4. David, the data on childhood Tylenol use and asthma risk is quite alarming, particularly so with comparisons to children given primarily ibuprofen (one could always say that kids who are sicker and have more fevers get more Tylenol, as sickness, infection and inflammation are definitely associated with bronchospasm.). The data is not conclusive. Ibuprofen is contraindicated in pregnancy (for different reasons for the first and third trimesters).

  5. Some company, or all companies, should formulate their acetaminophen tablets with an appropriate dose of N-acetyl cysteine. They probably won't because it would be tacit admission that acetaminophen isn't as safe as traditionally believed. Additionally, uninformed consumers are scared by the name of N-acetyl cysteine.

  6. I apologize if this is the wrong venue on which to ask you, but in line with the idea to reduce damage to the brain, is there any validity to this statement by Ray Peat, "The memory improvement that results from taking pregnenolone or thyroid (which is needed for synthesizing pregnenolone from cholesterol) is the result of turning off the dulling and brain-dissolving stress hormones, allowing normal responsiveness to be restored."? Based on this, the low carb, or even ketogenic diet, which seem to increase stress hormones seem contraindicative, no?

  7. I was just thrilled to learn about funky fries. Thanks Emily!

  8. Hi Emily -

    I have just found your blog and will state for the record that I love it.

    Regarding zinc and autism, there have been several papers that have found severely depressed levels in the autism population. A big one just came out last week:

    Infantile zinc deficiency: Association with autism spectrum disorders

    Elucidation of the pathogenesis and effective treatment of autism spectrum disorders is one of the challenges today. In this study, we examine hair zinc concentrations for 1,967 children with autistic disorders (1,553 males and 414 females), and show considerable association with zinc deficiency. Histogram of hair zinc concentration was non-symmetric with tailing in lower range, and 584 subjects were found to have lower zinc concentrations than -2 standard deviation level of its reference range (86.3-193ppm). The incidence rate of zinc deficiency in infant group aged 0-3 year-old was estimated 43.5 % in male and 52.5 % in female. The lowest zinc concentration of 10.7 ppm was detected in a 2-year-old boy, corresponding to about 1/12 of the control mean level.


    Keep it up!

    - pD