SAM-E
What is SAM-E?
SAM-E is a compound found naturally in the body, made from the amino acid methionine. It helps produce and regulate hormones and neurotransmitters and is critical for the regulation of cell growth and function.
SAM-E is a compound found naturally in the body, made from the amino acid methionine. SAM-E is integral to understanding much of the inflammation that affects those with autism.
In the USA, SAM-E is available as a supplement but in Europe a prescription is required. [2]
SAM-E has a variety of names including S-Adenosyl-L-methionine (also called S-adenosyl methionine), SAMe, or SAM-e, ademetionine in Europe, and also often abbreviated as SAM and AdoMet. [1]
SAM-E has been studied for its use in those with depression, osteoarthritis and improving liver function among those with liver diseases.[1] It is not recommended for those with bipolar disorder, those on medications designed to increase serotonin (antidepressants, l-tryptophan, St. John’s wort).[1]
SAM-E is essential to the biochemical process of methylation in the body. Methylation is simply the process of adding or taking away a carbon group to a substance in order to activate it or inactivate it. SAM-E functions as a methyl donor, which means that it donates/gives a carbon group to another substance.
This transfer of carbon groups is essential to life and is integral in many bodily processes including DNA production, mitochondrial function, neurotransmitter function, histamine metabolism and detoxification. If there is not enough SAM-E, as is often the case among those with autism, these processes will be impaired.
Methylation is often impaired in those with autism.[4] This may be in part because children with ASD are genetically inclined to have at least one MTHFR gene mutation. MTHFR stands for MethyleneTetraHydrofolate Reductase and it is an enzyme that is critical for the methylation process.
SAM-E also helps reduce the pro-inflammatory homocysteine by converting it to cysteine. It does this with the help of the micronutrients choline, betaine or TMG, folate (vitamin b9), pyridoxine (vitamin b6) and cobalamin (Vitamin B12). Cysteine is then used in the body’s production of glutathione, one of the body’s most important antioxidants. In this way, SAM-E helps to combat inflammation and oxidative stress in the body.
If folate metabolism is negatively impacted, as is often the case in those with MTHFR gene mutation, this process of converting homocysteine to methionine and cysteine to glutathione is stunted as well.
Sources of SAM-E
SAM-E is made in the body but the “ingredients” needed for our body to make it can be found in food, particularly the amino acid methionine. This can be found in [3]:
Note: Magnesium is needed for the conversion of methionine to SAM-E, so ensuring there are no magnesium deficiencies is very important and a magnesium supplement (like magnesium glycinate) may be beneficial. Deficiencies can be assessed with a micronutrient test.
Is SAM-E Beneficial for Autism?
Methylation & DNA
Individuals with ASD have substantially aberrant peripheral blood levels of Methionine, SAM, SAH, and the SAM/SAH ratio, which supports the association between impaired methylation capacity and ASD. [4]
Some studies suggest that supplementation with vitamin B12, either orally or via subcutaneous injection, can improve SAM-E levels in the body. [5]
Many studies have reported significantly lower plasma levels of methionine, SAM, homocysteine, cystathionine, cysteine, and total glutathione, and significantly higher concentrations of S-adenosylhomocysteine (SAH), adenosine, and oxidized glutathione. The lower SAM/SAH ratio is indicative of impaired methylation capacity and a lower glutathione with elevated oxidized glutathione represents impaired redox capacity. A meta-analysis of 22 studies confirmed a consistent finding of impaired DNA methylation in ASD and impaired DNA methylation has been associated with mitochondrial dysfunction in ASD. Impairments in the methylation cycle commonly lead to an accumulation in homocysteine, a finding which was reported in a number of studies in ASD. Treatments that have been shown to improve methylation and GSH production in ASD include methylcobalamin (mB12), betaine (anhydrous trimethylglycine), and leucovorin (folinic acid). [5]
In the brain, reduced SAM/SAH ratio will result in melatonin deficiency and impaired methylation of a number of biomolecules such as DNA, RNA and histones, reduced endogenous lipoic acid synthesis, reduced molybdenum cofactor synthesis and impaired porphyrin metabolism leading to mitochondrial dysfunction, porphyrinuria and impaired sulfation capacity. Furthermore depletion of SAM may also lead to the disturbed mTOR signaling pathway in a subgroup of ASD. [6]
Previous studies have demonstrated that valproic acid (VPA) can cause autistic-like behavioral changes in mice. In this study, these mice were treated with SAM-E. In males, 75% of the VPA-expressed genes were “repaired” by SAM administration; in females more genes were affected by VPA and only 52% of the VPA-affected genes normalized by SAM. This demonstrates a greater beneficial effect of SAM in males in most of the behavioral tests compared to females. Most of the genes whose expression were changed by VPA and corrected by SAM seem to be involved in ASD and/or several other diseases of the nervous system, or in cognition and memory, including genes involved in neuronal function and in inflammation. Genes of these two groups were also described as being associated with human ASD. The fact that SAM normalized their function may also explain the reversal of the autistic-like behavior and reduction of brain oxidative stress. [7]
Supplementation
There are very limited options for professional grade SAM-e supplements in liquid, chewable or powder form.
Examples of common SAM-E supplements include:
Tablet
Capsule/Softgel
DISCLAIMER: Before starting any supplement or medication, always consult with your healthcare provider to ensure it is a good fit for your child. Dosage can vary based on age, weight, gender, and current diet.
Note: All supplements are linked to Amazon for convenience, however, buying supplements on Amazon does not guarantee quality, as there are many “unverified resellers” selling nutrition supplements. To buy supplements that are verified to be sent directly to the consumer, you can create an account on the Autism Dietitian FullScript and search for the respective supplement under “Catalog”.
Authors
Edited by Brittyn Coleman, MS, RDN/LD, CLT
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[1] S-adenosyl-L-methionine (SAMe): In depth. NCCIH. Accessed May 14, 2022. https://www.nccih.nih.gov/health/sadenosyllmethionine-same-in-depth
[2] SAMe. Mayo Clinic. Published November 18, 2020. Accessed May 14, 2022. https://www.mayoclinic.org/drugs-supplements-same/art-20364924
[3] Methionine Food List. Texaschildrens.org. Accessed May 14, 2022. https://www.texaschildrens.org/sites/default/files/uploads/Cystinuria_handout.pdf
[4] Guo BQ, Ding SB, Li HB. Blood biomarker levels of methylation capacity in autism spectrum disorder: a systematic review and meta-analysis. Acta Psychiatr Scand. 2020;141(6):492-509.
[5] Rossignol DA, Frye RE. The Effectiveness of Cobalamin (B12) Treatment for Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. J Pers Med. 2021;11(8):784.
[6] Indika NR, Deutz NEP, Engelen MPKJ, Peiris H, Wijetunge S, Perera R. Sulfur amino acid metabolism and related metabotypes of autism spectrum disorder: A review of biochemical evidence for a hypothesis. Biochimie. 2021;184:143-57.
[7] Weinstein-Fudim L, Ergaz Z, Turgeman G, Yanai J, Szyf M, Ornoy A. Gender Related Changes in Gene Expression Induced by Valproic Acid in A Mouse Model of Autism and the Correction by S-adenosyl Methionine. Does It Explain the Gender Differences in Autistic Like Behavior. Int J Mol Sci. 2019;20(21):E5278.
