SAMe and Betaine TMG – The Mood Enhancing Power Couple


When your brain gets sick or ages, it is never just one biological mechanism, such as blood flow, that fails us, it is generally multiple mechanisms, such as blood flow, toxic buildup, nutrient depletion and inflammation.  This gives us the blueprint on how to help overall brain health – in multiple mechanisms that support healthy blood sugar, gut health, blood flow, antioxidant status and decreased inflammation.

Single mechanism interventions, such as just taking ginkgo or vitamin E by themselves, have not consistently worked in large scale studies. But when we use smart combinations, in a multiple mechanism approach, their effectiveness significantly improves.

Best Nutrients for a Healthy Brain

For example, with my patients, I often use:

  • Omega 3 fatty acids to support decreased overall inflammation
  • Ginkgo and vinpocetine to boost cerebral blood flow
  • Probiotics to support gut health … because the health of your gut affects the health of your brain
  • Alpha lipoic acid to help stabilize blood sugar levels and protect against nerve cell damage
  • Huperzine A and choline to boost acetylcholine levels, one of the main amino acids involved with learning and memory
  • Phosphatidylserine to support nerve cell membrane fluidity
  • N-acetyl-cysteine (NAC) for antioxidant support and detoxification

The science behind using natural supplements grows stronger every year, but we must stop looking for single bullet treatments, and instead help the brain in all of the ways it struggles.  This multiple-mechanism approach is what we used in our published brain rehabilitation study with football players where 80% of the players experienced significant improvement…and it’s what we use to help the people who come to our clinics.

The Power Couple

Another area that can benefit from this multiple mechanism approach is your mood. One of my favorite supplement combinations to help support a positive mood is betaine (trimethylglycine) and SAMe (S-AdenosylMethionine).

SAMe is a small, naturally occurring molecule which powers over 200 enzymes necessary for healthy cell growth, maturation, and specialization. In the brain, SAMe is required for nerve cells to make energy, maintain connectivity, and generate mood-related neurotransmitters. Taken alone, data from numerous clinical trials indicate SAMe strongly promotes positive mood. In fact, this nutrient has been so effective that it has been available by prescription in Europe for many years as an antidepressant.

And now it can work even better!

The Science

Recent research demonstrated that taking betaine at the same time as SAMe potentiated the effects of the SAMe on mood. In the clinical trial, subjects who received SAMe (750 mg/day) plus betaine (375 mg/day) performed better than SAMe alone (800 mg/day) on measures of worry, helplessness and worthlessness, agitation, and physical efficiency.

In yet another study, the efficacy of the combination of betaine and SAMe was tested against an antidepressant medication. After 6 and 12 months, both treated groups showed a noticeable improvement, although the group treated with SAMe plus betaine showed better results in terms of score on a depression rating scale, a number of individuals in remission, and side effects.

If you are looking for a natural, safe, and effective way to promote a positive mood, give betaine and SAMe a try!


5 1 vote
Article Rating
Notify of
Newest Most Voted
Inline Feedbacks
View all comments
Amanda Baker

I do have an important question – SAM-E is to be taken on an empty stomach and Betaine to be taken with food.. how do I proceed?

Keith Rowe


Hello. Thanks for your question. SAMe and Betaine don’t need to be taken at the same time. You can take them at different times (SAMe on an empty stomach and Betaine with food) within the same day and still have the same impact. Hope this helps. Have a nice day and thanks for reaching out to us.

BrainMD Team

Amanda Baker

In terms of Post Partum Depression, I am happy to report that this has Changed my life ♡♡♡!!! I cannot thank you enough for this article, and I have shared it 100 times over♡ !!!