Given the discussion yesterday about S-adenosylmethionine, I think this article is relevant and could even be important.
Obviously, it is up to each of us to decide for ourselves what to take. I suspect I'd be very wary.
Biologists warn against toxic SAMe ‘health’ supplement
Substance marketed online to ease range of joint and liver conditions, and to promote wellbeing, should not be used
A dietary supplement sold in the UK could be toxic and should not be used until it has been shown to be safe, an international group of biologists has warned.
The team, from Manchester and Kyoto universities, reported last week that the supplement – known as SAMe – can break down inside the body into substances that cause a wide range of medical problems, including kidney and liver damage
Short for S-adenosylmethionine, SAMe is marketed online in the UK as an agent that can help a range of conditions, including joints and liver diseases, and promote emotional wellbeing. But Jean-Michel Fustin, of Manchester University, said experiments that he and his collaborators had carried out had revealed that SAMe breaks down into adenine and methylthioadenosine in the body. These substances are known to be toxic, he added.
Fukumoto, K., Ito, K., Saer, B. et al. Excess S-adenosylmethionine inhibits methylation via catabolism to adenine. Commun Biol 5, 313 (2022). doi.org/10.1038/s42003-022-...
This was the info I remembered reading about SAMe from a member of TPA - it was posted in 2013 :
But beware - there is no point in buying any old SAMe - it has to be pharmaceutical grade and individually foil-blister packaged. The enteric coated tablets disintegrate and become poisonous when exposed for some time to air. I have been taking SAMe for years now - 800 mg per day (2 tablets) - and it is helping to keep at bay the pain of my osteoarthritis, keeps my liver clean, stabilizes my mood .... but all this comes at a price. I buy mine from vitacost in the US... I use vitacost's own brand, but others like 'Doctor's Best' are equally good.
Oh - and there is no point in looking to buy SAMe in the UK - it's prohibited to be sold here (EU regulations), but it is legal to import it from the US.... customs charges will apply, of course...
I did look up the price of the SAMe mentioned in the quote above some years ago, and what I remember about it is that it was eye-wateringly expensive by my standards.
I've never tried TMG (or heard of it before today) but one of its main effects apparently comes from it being a methyl donor. There are quite a few common supplements that are methyl donors, and some of them are much better known than TMG. (I hate buying supplements I've never heard of).
Although TMG supplementation decreases the amount of adipose tissue in pigs, research on human subjects has shown no effect on body weight, body composition, or resting energy expenditure when used in conjunction with a low calorie diet. The Food and Drug Administration of the United States approved anhydrous trimethylglycine (also known by the brand name Cystadane) for the treatment of homocystinuria, a disease caused by abnormally high homocysteine levels at birth. TMG is also used as the hydrochloride salt (marketed as betaine hydrochloride or betaine HCl). Betaine hydrochloride was once permitted in over-the-counter (OTC) drugs as a gastric aid in the United States. US Code of Federal Regulations, Title 21, Section 310.540, which became effective on November 10, 1993, banned betaine hydrochloride from being used in OTC products due to insufficient evidence to classify it as "generally recognized as safe and effective".
TMG supplementation may cause diarrhea, stomach upset, or nausea. TMG supplementation lowers homocysteine but also raises LDL-cholesterol in obese individuals and renal patients.
I think the reference to Betaine HCL is interesting. Not mentioned so often recently, but used to be discussed very frequently here - re the reasonably common issue of low stomach acid in those who are hypothyroid.
I couldn't work out from the article I linked whether it was exactly the same supplement as Betaine HCL with a different name, so I didn't mention it. I could never tolerate Betaine HCL - my stomach isn't happy with acids. Even ascorbic acid in amounts higher than about 1g is more than I can tolerate.
The usual acid we secrete in our stomachs is HCl. I suspect (pure guesswork) that taking Betaine-HCl is a way of getting HCL into our stomachs without burning our mouths and throats and dissolving our teeth on the way in!
So it seems reasonable to suggest that Betaine-HCl simply breaks apart (mechanism unknown to me) in our stomachs. Thereby making them acidic as they should be. With Betaine just carrying on through. No idea if it will get absorbed.
The first part of the methylation cycle uses MTHRF that passes methyl groups to functions that need them, for example folate becomes methyl-folate that interacts with say, homocysteine which then becomes methylated and so becomes methionine (these are the well known ones) until they get to SAMe that then distributes them onto where they are needed for bodyily function; ie methylated serotonin becomes melatonin, or excess histamine/oestrogen that require methylation to be excreted.
With the exception of a small proportion used to make glutathione, SAMe then becomes homocysteine itself which is both the start and end of the methylation cycle, so starting again. This demonstrates how keeping our MTHFR strong with optimised Vit B12 & folate helps infinite bodily functions.
Betaine is also referred to as TMG, and is a methyl group donor that functions within methionine, so metabolising/reducing high serum homocysteine levels. (Edited to rewrite incorrect sentence).
Betaine HCI is a protonated form of TMG, the betaine being a good carrier molecule for the HCI which is a good source of extra stomach acid for those of us that are low. It is usually dosed with pepsin that promotes digestion. By keeping stomachs pH between 1.5 - 2.5 it provides a perfect environment for good gut health by killing microorganisms (bacteria and yeast), allowing correct stomach emptying (instead of heartburn/GERD/etc), and protein digestion and micronutrient absorption (magnesium, zinc, copper, iron, selenium, etc.) Glutamic acid HCI can be taken by those sensitive to betaine.
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Recent blood tests , Vit B 12 and folic acid
hypothyroidism and peripheral neuropathy 
Six Months later - upcoming meeting with my MD (input needed) 
New blood test results received, and ready to switch from Levo to NDT.
