TMG: Benefits, Side Effects, Best Time to Take It & More

TMG

(Trimethylglycine, Betaine, Betaine Anhydrous)

Evidence: High
Potential Benefits: High
Safety: Very High

What is TMG?

TMG (also known as trimethylglycine and betaine anhydrous) is an amino acid found mainly in beetroot and leafy greens. As a supplement, trimethylglycine is most beneficial if you are deficient in choline or if you are taking high doses of any form of vitamin B3 (such as nicotinic acid, NR, and NMN). Even if neither of these applies to you, trimethylglycine is still worth consideration as it is one of the safest supplements and it can improve some aspects of your health beyond the baseline. This article is about the main benefits of TMG, its potential side effects, the best time to take it, and more.

Potential benefits

It is important to note that all of the potential benefits mentioned below are dose-dependent. Generally, the higher the dose, the more pronounced the effects are. However, they do reach a plateau at a certain point. We will discuss the best dosing protocol later in this article.

Many possible benefits fall under the umbrella of ‘correcting a choline deficiency’ and are therefore not mentioned in the article. If you are deficient in choline, TMG supplements can affect your cognition, performance, and overall health in a remarkably positive way.

Major benefits

Correcting or preventing a choline deficiency – While betaine (trimethylglycine) cannot fully replace choline in its functions, it can decrease your choline needs by about a half. This is because TMG is vital in the methylation process and a lot of choline you consume has to convert into trimethylglycine to support methylation. If you get enough TMG, the choline you consume can instead be utilized for other processes, such as forming the neurotransmitter acetylcholine. Most adults need about 550 mg of choline. Betaine (TMG) can replace about a half, so 275 mg. This means that if you consume 275 mg or more of betaine, you only need to get 275 mg of choline to avoid a deficiency. If you are experiencing symptoms of deficiency or know that your choline levels are too low, helping correct a deficiency is the main benefit of trimethylglycine.
Minimizing the side effects of high-dose vitamin B3 – Taking high doses of niacinamide, nicotinic acid, NR, or NMN, can be incredibly beneficial for slowing down aging and preventing certain diseases. However, these supplements can also cause some side effects, such as liver damage, by taxing your methylation system and depleting your body of compounds involved in methylation. TMG is one of those compounds. Taking trimethylglycine along with any form of vitamin B3 will help you minimize or completely eliminate this problem. For optimal effects, pair nicotinic acid or niacinamide with an equal amount of TMG. If you’re taking NR or NMN, combine it with half the dose of trimethylglycine.

Minor benefits

Reduced homocysteine – 3 grams of TMG (trimethylglycine) have been shown to decrease homocysteine levels in healthy individuals by about 10% and by 20-40% in people with elevated homocysteine.
Reduced folate and vitamin B12 deficiency – TMG can replace folate and vitamin B12 in some of their functions related to methylation. While it is important to address both of these deficiencies, TMG can help prevent the damage before you get to optimal levels of folate and B12. This is also why low MTHFR activity can increase your need for TMG if you don’t get enough folate or B12. Low MTHFR activity increases your need for trimethylglycine and choline in general by 60-100%.
Increased training volume – One study found that taking trimethylglycine increases training volume by about 6.5%.
Reduced liver fat – TMG can reduce liver fat and prevent fatty liver disease. People with NAFLD (non-alcoholic fatty liver disease) will benefit the most.
Reduced liver damage – People who take high doses of vitamin B3 or those with NAFLD (non-alcoholic fatty liver disease) will benefit the most.
Reduced cortisol – TMG can decrease cortisol by about 6.1% (measured after exercise in a fasted state).
Increased power output – This effect has also been shown in one study but has later been disproven so TMG is unreliable in this regard.
Increased lifespan – While there are no good human studies directly looking at the relationship between trimethylglycine and lifespan, TMG has been shown to increase lifespan in mice by 4-6%.

Possible side effects

These side effects are dose-dependent. The risk for them increases (often linearly but sometimes exponentially) as you increase the dose. Some of the side effects only apply to very high doses.

Diarrhea – This side effect isn’t dangerous and typically only occurs at high doses.
Body odor – 7-10 grams may also cause a fishy body odor in some people.
Sweating and salivation – These side effects have also been associated with doses of multiple grams and are a means for the body to get rid of the excess trimethylglycine.
Increased LDL cholesterol – More precisely, one study has shown no difference in LDL cholesterol levels but a mild decrease in placebo in those who take high amounts of trimethylglycine. Therefore, TMG supplements only seem to slightly increase LDL cholesterol relative to placebo but not in general. No change in HDL cholesterol has ever been noted.
Increased IGF-1 – High doses of betaine (TMG) have been shown to increase IGF-1 by 7-8%.
Contamination – Contaminated supplements are uncommon in the USA and other well-regulated countries. However, if you wish to buy products from China, India, or other countries without strict regulations, beware that the supplements may be contaminated. Either way, you need to choose the brand you order from wisely. It is highly recommended to check the certificates or read through some reviews for the specific product before you buy it. The FDA (Food and Drug Administration) has the power to regulate dietary supplements but can only do so after they have been on the market for a while. That’s because supplement companies are not obligated to announce to the FDA when releasing a new product on the market. The FDA has to discover the product and test it for potential impurities, which can take a lot of time. During that time, the supplement can be sold on the market even if it’s impure. Also, the supplement companies can change their manufacturers at any time without announcing it to the FDA.

Who should not take TMG?

You should probably avoid taking the supplement if you:

already consume enough betaine from food and don’t take vitamin B3
experience a severe adverse reaction after taking the supplement
take SAMe (you may not need to take TMG in this case since SAMe replaces many of its functions)

Who will benefit the most?

You should consider taking the supplement if you:

take high doses of any form of vitamin B3 (including nicotinic acid, niacinamide, NR, and NMN)
suffer from NAFLD
don’t get enough choline + betaine (TMG) from food
experience symptoms of choline deficiency, or you know you are deficient based on blood tests
are on a plant-based diet (not eating eggs makes it harder to get enough choline)
have low MTHFR activity (low MTHFR activity increases your need for folate and vitamin B12 but TMG can replace folate and vitamin B12 in some of their functions related to methylation; people with low MTHFR activity usually need 60-100% more TMG+choline, assuming they also don’t get enough riboflavin)
are deficient in folate or vitamin B12 (while it is important to address both of these deficiencies, TMG can partially help by replacing folate or B12 in some functions)
have a high budget for supplements (assuming that the supplement doesn’t contain impurities, it is one of the safest supplements on the market and rarely does more harm than good if you stick to regular doses)

Symptoms of choline deficiency

The most common signs of deficiency include:

low energy
forgetting and poor memory
difficulty concentrating
learning disabilities
muscle aches
mood swings
nerve pain

Keep in mind that these signs are just indications of a deficiency. If you experience some or even most of them, it does not necessarily mean you need more choline. On the other hand, some people may be deficient even though they are completely asymptomatic.

With that said, if you experience many or most of these symptoms, there is a high chance that you are not getting enough of this nutrient. The more of these symptoms you have and the more severe they are, the more likely you are to have a deficiency.

How much TMG should you take?

If you wish to use TMG to support your choline status, 275 mg should be enough for most people. This is because the AI (adequate intake) for choline is 550 mg for most adults, and betaine (TMG) can mostly replace choline in the methylation process.

Keep in mind that TMG itself can’t ensure you are getting enough choline, it can only drop your need for the nutrient to around 275 mg.

Beware that some things increase your need for TMG. For example, low MTHFR activity increases your need for TMG by 60-100%. Taking niacinamide or nicotinic acid increases your need for TMG by about 1 mg per every mg taken. If you’re taking NR or NMN, you will need at least half the dose of TMG (in mg) to ensure you’re not depleting your system of TMG and not hurting the methylation process by taking these forms of vitamin B3.

Certain nootropics, such as racetams, also increase the amount of choline you need. However, TMG cannot cover this increased need as it has to do with the acetylcholine pathway and not methylation.

TMG has mostly been studied in doses of 2-6 grams, which is why many people recommend doses in this range. However, lower doses, seem to be just as effective for most purposes. A daily dose of 1-2 grams seems to be optimal for most people.

TMG is one of the safest supplements and even very high doses (6-15 grams) seem to be safe in the short term. However, high doses of TMG may cause problems for some people if they take the supplement for a prolonged period. Do not take more than this amount unless you have a great reason to do so.

The higher the dose you take, the higher the risk for side effects. While the supplement is extremely safe, taking more than 3 grams daily should not be necessary and is not recommended unless you have a great reason to do so.

Food sources of betaine (TMG)

100 grams of fresh beetroot, frozen spinach, and some other leafy greens provide around 140 mg of betaine. Wheat germ is also a fantastic source. As little as 70 grams can provide most of your choline needs (by supplying both choline and betaine).

Keep in mind that you can only get around half of the choline requirements from betaine. Betaine can mostly replace choline in the methylation process but not in other processes, such as making acetylcholine.

If you wish to get 550 mg of choline from food (which is an adequate intake for most adults), you should only need 275 mg of choline if you get 275 mg of betaine. If you eat or supplement with more than 275 mg of betaine, you will still need the 275 or so mg of choline.

The richest food sources of choline are egg yolks and liver. As little as 4 eggs or 200-300 grams of liver should provide enough choline.

Nuts, seeds, vegetables, legumes, and some grains are also great sources of this nutrient.

The easiest way to find out how much choline and betaine you are getting in your diet is with Cronometer.com – this free app allows you to track all vitamins, minerals, and more.

Best time to take TMG

Trimethylglycine (TMG) is water-soluble, which means you don’t have to take it with food to absorb it well. Taking the supplement with food is better if it causes stomach upset when you take it on an empty stomach.

Whether you take TMG in the morning or the evening doesn’t really matter. You can try both options and see which works better for you.

If you are taking any form of vitamin B3, take TMG together with the B3.

Interactions with other supplements

Vitamin B3
TMG can protect against potential liver toxicity caused by vitamin B3 supplements. For optimal effects, pair nicotinic acid or niacinamide with an equal amount of TMG. If you’re taking NR or NMN, combine it with half the dose of TMG.
Riboflavin
Riboflavin can reduce the fishy smell that occurs mainly in people with a mutation in the FMO3 gene when they take high doses of TMG.

Where to buy TMG

Amazon seems to be the best option for ordering TMG supplements in most countries. They offer some very affordable products backed by many positive reviews. Also, you can choose from a wide range of brands without having to search through other markets on the internet.

Beware some brands display the dosage per serving instead of per pill or capsule. Therefore, you may accidentally buy something less potent than you intended. Do not fall for this marketing trick.

FAQ

You can take the supplement daily and do not need to cycle it. However, it is certainly not a problem if you don’t take it daily. Not taking the supplement every once in a while could lead to better absorption, but no studies have proven this yet.

All of these options are fine. The two most important things to consider are the price and dosing. Powders are almost always the cheapest form. However, to dose them correctly, you may need a highly accurate scale (preferably 0.001g). You can get one for as little as $20 from Amazon. Dosing the powders also takes some time that can add up over months or years. The disadvantage of capsules is that they are sometimes made of unethical ingredients, such as bovine gelatine.

Yes. The supplement doesn’t impact your sleep in a negative way. Some anecdotal reports suggest it may actually improve your sleep.

TMG supplements rarely go bad, but they can lose potency over time.

Keep trimethylglycine in a cold, dark, and dry place, and they will remain just as potent for many months or even years.

The supplement doesn’t directly reduce acne, unfortunately.

While toxicity is not a concern unless you take extremely high doses, too much TMG in the system can cause some problems, such as a fishy odor, excess sweating, and diarrhea. To stay on the safe side, it is best to stay below 6 grams a day to prevent or minimize these side effects.

You may need more trimethylglycine if you:
– take high doses of any form of vitamin B3 (including nicotinic acid, niacinamide, NR, and NMN)
– don’t get enough choline + betaine (TMG) from food
– have low MTHFR activity (low MTHFR activity increases your need for folate and vitamin B12 but TMG can replace folate and vitamin B12 in some of their functions related to methylation; people with low MTHFR activity usually need 60-100% more TMG+choline, assuming they also don’t get enough riboflavin)- are deficient in folate or vitamin B12 (while it is important to address both of these deficiencies, choline can partially help by replacing folate or B12 in some functions)
– are deficient in folate or vitamin B12 (while it is important to address both of these deficiencies, TMG can partially help by replacing folate or B12 in some functions)
– experience symptoms of choline deficiency, or you know you are deficient based on blood tests
– suffer from NAFLD
– are on a plant-based diet (not eating eggs makes it harder to get enough of the nutrient)

In the long-term, it typically takes about a month after you start taking the supplement to start noticing the benefits.

The majority of TMG supplements on the market are vegan-friendly but always check the label to be sure.

Trimethylglycine is water-soluble, which means you don’t have to take it with food to absorb it well.

No, it doesn’t. The supplement does not interfere with fasting in any significant way.

While these two compounds are similar in many ways, TMG doesn’t provide bioavailable glycine.

References

Most of the information provided in this guide is supported by scientific research that can be found and verified in the PubMed medical library. We highly encourage you to use the library to verify anything said in this article. We excluded from consideration studies that are either confounded or have a high conflict of interest.

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