Combination of S-adenosylmethione and betaine combats mild depression
If pharmacological antidepressants do not work well, mildly depressed patients may benefit from supplementation with S-adenosylmethionine and betaine. The combination of S-adenosylmethionine and betaine may even exceed the effect of the pharmacological antidepressant amitriptyline. At least that's the gist of two Italian human studies that we happened to find on the web.Study 1
The researchers experimented with 46 mildly depressed people who had been taking pharmacological antidepressants for at least six months but had not responded to them.

The researchers gave half of their subjects a supplement every day for 3 months with 800 milligrams of S-adenosylmethionine [divided into 2 doses per day], and the other half every day 750 milligrams of S-adenosylmethionine plus 375 milligrams of betaine per day [divided between 3 doses per day].
The researchers used a supplement from the Italian Omeopiacenza. It is called DDM Metile. The lead author of the study, Francesco Di Pierro of the research company Velleja Research, [More] [Even more] is the spiritual father of DMM Metile. We therefore consider the study sponsored.During the 90 days that the experiment lasted, the subjects who combined S-adenosylmethione with their antidepressants showed progress. The classic symptoms of depression, such as anxiety and unrest, decreased, while the subjects' estimate of their physical health increased.
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The combination of S-adenosylmethionine and betaine had the same effect - only stronger."On the basis of study results, it may be assumed that the administration of S-adenosylmethionine plus betaine is a better adjunctive therapy than the administration of S-adenosylmethionine alone in subjects with mild-to-moderate depression who are low responders to conventional antidepressive drugs", write the Italians.
Study 2
Di Pierro and colleagues published yet another study in 2015 with mildly depressed patients as subjects. [Int J Gen Med. 2015;8:73-8.] In this study, they compared the antidepressant effect of a supplement containing betaine and S-adenosylmethionine with that of the pharmacological antidepressant amitriptyline.

After 6-12 months, the number of people with relatively high depression scores in the supplementation group had decreased by 50-64 percent. In the amitriptyline group, this was only 13-4 percent.
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Side effects were significantly less common among supplement users than amitriptyline users.
J Multidiscip Healthc. 2015;8:39-45.