I have had a lot of inquiries into methylation and Autism, the why, how , when and what of it all. It certainly is a complex topic but let me do my best to examine the research and make it useful for everyone. Warning, this is a large topic and I never did well in language arts as a kid. The field of research in ASD is thick and cumbersome like a double big mac, so let's break into quater pounders if you will.
The best place to start with this topic is at the level of oxidation and anti-oxidants. Everyone has heard of anti-oxidants and their benefits but why are they beneficial. Well, oxidation is a normal process in the body things like peroxides (1) are created in order to destroy bacteria and other problematic organisms amongst other things. The problem is, once this oxidant (reactive oxygen species ) is done with it's job it needs to be cleaned up per se, that's were anti-oxidants come into play. If you don't have enough anti-oxidants or the right type you risk oxidation damaging your cells and ultimately causing ill health. Almost all diseases have components of oxidative stress but just any old anti-oxidant won't do.
So what is methylation and how do we best categorize it? It is aptly named the methylation cycle for a reason, it is a continuous circle or cycle in the body that actively re-cycles molecules into usable forms. Think of it like a nascar track, it has no end and the cars are the molecules that need to be serviced just like our body. That is the cars move along this track just like methyl donors (b12,tmg etc) revolve around this cycle. Every good racetrack has pit stops, in this case the methylation cycle has three main ones, methionine, homocysteine and SAM. At each pitstop something different is added or removed from the car, it may be the brakes or a refill of gas, whatever it is each stop is important to ensure the cars move along the track smoothly.
If one pit stop is ensured with the job of changing the tires and doesn't complete it's task the next pit stop will have more work and likely do a poor job. This is exactly the issue we see in Autism(ASD), do to lack of workers/tools at the pit stop (methyl donors) or poorly skilled workers (enzyme defects) the cars (our bodies) don't function correctly.
But what exactly does not functioning properly mean? Well a multitude of research studies have indicated that methylation is indeed impaired in ASD (1,2,3,4,5,6). Properly working methylation is required for cognition, behaviour, anti-oxidant defenses, Protein activation etc. Methylation helps keep the stuff under the hood (the brain/body) working smoothly. The cycle also produces a substance called Glutathione, the bodies master anti-oxidant, It is the gas of the car if you will, other anti-oxidants are regular, but glutathione is premium unleaded gas, the stuff no one buys.
In ASD low levels of glutathione have been found (2,3,4), High levels of homocysteine, one of the pitstops that supplies the gas (glutathione) and high levels of oxidative stress (wear and tear). How can this be corrected? supplying the pitstops with the proper tools (methyl donors) seems to resolve this problem. Improvements in all biomarkers related to poor methylation improved when proper dosages of these nutrients were supplied,that is the pit stops worked properly when the right tools and workers were supplied.
Improvements in language, behaviour (aggression, tantrums) socialization have been noted with therapies aimed at correcting this cycle and combating oxidation. Improving methylation increases glutathione, reduces oxidative stress, improves neurotransmitter function and keeps our genes working correctly(2,6,7,8,9).
Why is this happening in ASD? no one is sure it's likely a host of things combining to cause this issue. Enzyme deficiencies and defects have been noted, reduced intake of raw materials (methyl donors) is also a factor and the genetics of autism perhaps holds some further clues.
some insights from the researchers:
"An increased vulnerability to oxidative stress and a decreased capacity for methylation may contribute to the development and clinical manifestation of autism. " (2).
"Compared with controls, significantly higher improvement ratings were observed in treated children over a mean period of 4 months in verbal communication, receptive and expressive language, attention and stereotypical behavior. Approximately one-third of treated children demonstrated moderate to much improvement" (7).
my goal is to take the guesswork out of the data for my patients and help develop workable, science based strategies for treatment.
I would love any comments or questions, debate sparks innovation.
References:
1.Al-Gadani Y, El-Ansary A, Attas O, Al-Ayadhi L. Metabolic biomarkers related to oxidative stress and antioxidant status in Saudi autistic children. Clin Biochem. 2009 Jul;42(10-11):1032-40.
2. James SJ, Cutler P, Melnyk S, Jernigan S, Janak L, Gaylor DW, Neubrander JA. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr. 2004 Dec;80(6):1611-7.
3.Pastural E, et al. Novel plasma phospholipid biomarkers of autism: Mitochondrial dysfunction as a putative causative mechanism. Prostaglandins Leukot Essent Fatty Acids. 2009 Oct;81(4):253-64.
4.Blaylock, R. Interactions of cytokines, excitotoxins, and reactive nitrogen and oxygen species in autism spectrum disorders. J Amer Nutr Assoc 2003: 6: 21-35.
5.James SJ, et al. Efficacy of methylcobalamin and folinic acid treatment on glutathione redox status in children with autism. Am J Clin Nutr. 2009 Jan;89(1):425-30.
6.Krajcovicova-Kudlackova M, Valachovicova M, Mislanova C, Hudecova Z, Sustrova M, Ostatnikova D. Plasma concentrations of selected antioxidants in autistic children and adolescents. Bratisl Lek Listy. 2009;110(4):247-50.
7.Mol Psychiatry. 2012 Jan 10. doi: 10.1038/mp.2011.175. [Epub ahead of print]Cerebral folate receptor autoantibodies in autism spectrum disorder.Frye et al.
8.Neurology. 2005 Mar 22;64(6):1088-90.
Cerebral folate deficiency with developmental delay, autism, and response tofolinic acid.Moretti P, et al.
Source
9.J Altern Complement Med. 2011 Mar;17(3):271-4.
Effectiveness of nutritional supplements for reducing symptoms in autism-spectrum disorder: a case report.XIa, RR.
10.Magnes Res. 2006 Mar;19(1):53-62.Improvement of neurobehavioral disorders in children supplemented withmagnesium-vitamin B6. II. Pervasive developmental disorder-autism.Mousain-Bosc M et al
The best place to start with this topic is at the level of oxidation and anti-oxidants. Everyone has heard of anti-oxidants and their benefits but why are they beneficial. Well, oxidation is a normal process in the body things like peroxides (1) are created in order to destroy bacteria and other problematic organisms amongst other things. The problem is, once this oxidant (reactive oxygen species ) is done with it's job it needs to be cleaned up per se, that's were anti-oxidants come into play. If you don't have enough anti-oxidants or the right type you risk oxidation damaging your cells and ultimately causing ill health. Almost all diseases have components of oxidative stress but just any old anti-oxidant won't do.
So what is methylation and how do we best categorize it? It is aptly named the methylation cycle for a reason, it is a continuous circle or cycle in the body that actively re-cycles molecules into usable forms. Think of it like a nascar track, it has no end and the cars are the molecules that need to be serviced just like our body. That is the cars move along this track just like methyl donors (b12,tmg etc) revolve around this cycle. Every good racetrack has pit stops, in this case the methylation cycle has three main ones, methionine, homocysteine and SAM. At each pitstop something different is added or removed from the car, it may be the brakes or a refill of gas, whatever it is each stop is important to ensure the cars move along the track smoothly.
If one pit stop is ensured with the job of changing the tires and doesn't complete it's task the next pit stop will have more work and likely do a poor job. This is exactly the issue we see in Autism(ASD), do to lack of workers/tools at the pit stop (methyl donors) or poorly skilled workers (enzyme defects) the cars (our bodies) don't function correctly.
But what exactly does not functioning properly mean? Well a multitude of research studies have indicated that methylation is indeed impaired in ASD (1,2,3,4,5,6). Properly working methylation is required for cognition, behaviour, anti-oxidant defenses, Protein activation etc. Methylation helps keep the stuff under the hood (the brain/body) working smoothly. The cycle also produces a substance called Glutathione, the bodies master anti-oxidant, It is the gas of the car if you will, other anti-oxidants are regular, but glutathione is premium unleaded gas, the stuff no one buys.
In ASD low levels of glutathione have been found (2,3,4), High levels of homocysteine, one of the pitstops that supplies the gas (glutathione) and high levels of oxidative stress (wear and tear). How can this be corrected? supplying the pitstops with the proper tools (methyl donors) seems to resolve this problem. Improvements in all biomarkers related to poor methylation improved when proper dosages of these nutrients were supplied,that is the pit stops worked properly when the right tools and workers were supplied.
Improvements in language, behaviour (aggression, tantrums) socialization have been noted with therapies aimed at correcting this cycle and combating oxidation. Improving methylation increases glutathione, reduces oxidative stress, improves neurotransmitter function and keeps our genes working correctly(2,6,7,8,9).
Why is this happening in ASD? no one is sure it's likely a host of things combining to cause this issue. Enzyme deficiencies and defects have been noted, reduced intake of raw materials (methyl donors) is also a factor and the genetics of autism perhaps holds some further clues.
some insights from the researchers:
"An increased vulnerability to oxidative stress and a decreased capacity for methylation may contribute to the development and clinical manifestation of autism. " (2).
"Compared with controls, significantly higher improvement ratings were observed in treated children over a mean period of 4 months in verbal communication, receptive and expressive language, attention and stereotypical behavior. Approximately one-third of treated children demonstrated moderate to much improvement" (7).
my goal is to take the guesswork out of the data for my patients and help develop workable, science based strategies for treatment.
I would love any comments or questions, debate sparks innovation.
References:
1.Al-Gadani Y, El-Ansary A, Attas O, Al-Ayadhi L. Metabolic biomarkers related to oxidative stress and antioxidant status in Saudi autistic children. Clin Biochem. 2009 Jul;42(10-11):1032-40.
2. James SJ, Cutler P, Melnyk S, Jernigan S, Janak L, Gaylor DW, Neubrander JA. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr. 2004 Dec;80(6):1611-7.
3.Pastural E, et al. Novel plasma phospholipid biomarkers of autism: Mitochondrial dysfunction as a putative causative mechanism. Prostaglandins Leukot Essent Fatty Acids. 2009 Oct;81(4):253-64.
4.Blaylock, R. Interactions of cytokines, excitotoxins, and reactive nitrogen and oxygen species in autism spectrum disorders. J Amer Nutr Assoc 2003: 6: 21-35.
5.James SJ, et al. Efficacy of methylcobalamin and folinic acid treatment on glutathione redox status in children with autism. Am J Clin Nutr. 2009 Jan;89(1):425-30.
6.Krajcovicova-Kudlackova M, Valachovicova M, Mislanova C, Hudecova Z, Sustrova M, Ostatnikova D. Plasma concentrations of selected antioxidants in autistic children and adolescents. Bratisl Lek Listy. 2009;110(4):247-50.
7.Mol Psychiatry. 2012 Jan 10. doi: 10.1038/mp.2011.175. [Epub ahead of print]Cerebral folate receptor autoantibodies in autism spectrum disorder.Frye et al.
8.Neurology. 2005 Mar 22;64(6):1088-90.
Cerebral folate deficiency with developmental delay, autism, and response tofolinic acid.Moretti P, et al.
Source
9.J Altern Complement Med. 2011 Mar;17(3):271-4.
Effectiveness of nutritional supplements for reducing symptoms in autism-spectrum disorder: a case report.XIa, RR.
10.Magnes Res. 2006 Mar;19(1):53-62.Improvement of neurobehavioral disorders in children supplemented withmagnesium-vitamin B6. II. Pervasive developmental disorder-autism.Mousain-Bosc M et al
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