Best TMG supplement

It seems people have always wanted to live longer and healthier lives. Folks were writing about the Fountain of Youth more than 2,000 years ago,1 and the word “longevity” has cropped up in scientific literature with increasing frequency since the 1800s.2 We’re engaged in the same pursuit even today, possibly with more fervor than ever.3

The ongoing interest in longevity has led to a clearer understanding of the biological factors that affect our lifespans. Now we know that one key to slower and healthier aging is a process called DNA methylation, and a principal player in the process is a molecule called trimethylglycine (TMG), also known as betaine.4 5 As a health supplement, TMG has been the subject of studies on aging-related pathologies linked to the liver and heart, as well as quality-of-life markers like physical strength and gastrointestinal health. But to what extent can a TMG supplement help in these areas?

We did the research to find out and identified the four TMG supplements that best aligned with our findings.

See our summary of recommendations for the rundown. Then read further to see how we reached our conclusions.

Over the past two decades, Innerbody Research has helped tens of millions of readers make more informed decisions about staying healthy and living healthier lifestyles.

To find the market’s best TMG supplements, we first devoted several weeks to studying TMG’s role in the body and the amounts needed to carry it out. With a solid understanding of its purpose, mechanisms, and optimal doses, we were able to identify four brands that met our evaluative standards. We ordered those brands, tried them, and recorded our experiences along the way. By the time we finished researching for and writing this guide, we’d spent nearly 250 hours head-deep in the TMG supplement space.

Additionally, like all health-related content on this website, this guide was thoroughly vetted by one or more members of our Medical Review Board for accuracy and will continue to be monitored for updates by our editorial team.

Our criteria for evaluating the best TMG supplements were those that are most likely to inform consumers’ purchasing decisions: effectiveness, safety, cost, and convenience. Most of these criteria required a very nuanced assessment of what makes for a good TMG supplement, as we discuss below.

Effectiveness

Winner: NOW Sports Betaine Powder

In choosing our winner for effectiveness, our chief concern was whether the amount of TMG alone aligned with those of successful studies for the most common uses. For example, TMG is commonly used to support physical strength or reduce cardiovascular risk, so what product provides a clinically relevant dose to achieve the desired effect?

NOW Sports Betaine Powder does. Or at least its 1.6g per serving comes closest.

One of the compasses that guided us to this conclusion was a 2009 placebo-controlled study published in the Journal of the International Society of Sports Nutrition, a reputable and frequently cited scientific publication.6 The study specifically looked at TMG’s impact on muscle endurance, power performance, and rate of fatigue in active young men. In it, subjects who received two daily 1.25g doses of TMG demonstrated at least a 90% increase in peak power when performing a squat exercise compared to the placebo group, an outcome similar to what might be expected with creatine supplementation.7 Two other studies — a review from 2013 and another from 20228 9 — assessed TMG’s potential as a cardiovascular risk reducer and arrived at 4g as the minimum effective daily dose to that end. NOW recommends two servings of its TMG per day for 3.2g in total, which falls neatly between the clinical dose for strength performance and the maximum dose for cardiovascular benefits. Even a single dose may be enough to provide some benefit, per a 2003 study.10

For quick reference, here’s a table showing NOW’s TMG dose compared to our other top recommendations and how many servings you’d need of each supplement to hit clinical doses:

With NOW, you need less supplement to reach potentially beneficial thresholds. With ProHealth, Thorne, and Life Extension, the lower end of the serving range covers only the amount needed for power performance, so you’d need to take additional servings to see potential cardiovascular benefits. (Also, because those other brands recommend only one serving per day, taking more than the label-recommended amount reduces the cost value.)

Safety

Winner: Life Extension TMG

A maximally safe TMG supplement synergizes high-standard manufacturing practices, a low-risk ingredient list, and a minimally effective dose. In the following ways, Life Extension TMG succeeds in all three measures:

• The company is registered with NSF International, which speaks to its compliance with rigorous public health and safety standards.11
• Its raw materials and finished products are third-party tested.
• Its TMG supplement contains no other active ingredients that could elevate its side effect profile.
• The 1g of TMG in every serving is well below the 4g threshold that can potentially increase total and low-density lipoprotein (LDL) cholesterol.12
• The capsules are vegetable-based and gluten-free, so they’re suitable for vegetarians and the gluten-intolerant.

The other brands in this guide fail to meet the same safety standards as Life Extension, in small ways. ProHealth’s 1g of resveratrol (from Japanese knotweed, a potential allergen)13 can potentially interact with certain drugs;14 Thorne contains pepsin derived from pigs, so it isn’t suitable for vegetarians; and NOW’s higher suggested dose of TMG might be too high for some people. These risks posed by ProHealth, Thorne, and NOW are relatively minor but not negligible.

Cost

Winner: NOW Sports Betaine Powder

In our summary of recommendations, you’ll notice we have one choice for “Budget pick” and another for “Lowest up-front cost.” The distinction relates to long-term and immediate use, respectively. NOW Sports is the most cost-effective option because a single bottle provides 106 servings of 1,600mg each, compared to Life Extension’s 30 servings of 500mg. So while NOW Sports ($17.99) costs 54% more up front than Life Extension ($9.75), it should last 88%-350% longer depending on how many servings you take per day. On a per-serving level, NOW Sports is almost half the cost ($0.17 versus $0.33). And in terms of cost per gram of TMG, it’s around three times less (approximately $0.11 versus $0.33).

But for many people, the biggest financial needle mover isn’t cost-effectiveness; it’s up-front cost. In that case, Life Extension TMG is the best option, at least as a starting point. Its sub-$10 base price and lower dosage could make it especially appealing to beginners or the TMG-curious.

Our other two recommendations, ProHealth and Thorne, represent higher price tiers. ProHealth is the most expensive option in this guide, with a base of $76.86 and 30 servings ($2.56 per serving), while Thorne has the second-highest price point at $47 and 112 servings ($0.21-$0.42 per serving depending on your preferred serving size). Thorne’s price point is reasonable, especially with how many servings come in a bottle, but ProHealth might be out of financial reach for some, likely due to its complex list of active ingredients.

Convenience

Winner: Life Extension TMG

To us, convenience means ease of use and an easygoing customer experience, irrespective of the dose. With these two criteria taken together, Life Extension stands above the competition.

Let’s start with customer experience, where Life Extension stands out for its 365-day satisfaction guarantee. Besides being one of the best return policies in the whole supplements market, this guarantee period is more than six times longer than Thorne’s and almost four times longer than ProHealth’s (NOW Sports has no try-first policy at all).

Concerning ease of use, all of our TMG recommendations stand more or less equal, but Life Extension and Thorne will be easier to take for many users. That’s because they’re soft-body capsules, as opposed to powders like NOW and ProHealth. Even for people who don’t like swallowing capsules, it’s hard to deny that capsules are easier than powders to take on the go. The capsules disappear into pill carriers and pockets and go down flavorlessly with a gulp of water, whereas powders require that you have a larger volume of liquid in a vessel, and they leave a faint taste on the tongue. ProHealth is available as a capsule supplement, too, but you’re instructed to take four per serving — a relatively large quantity.

Between our two powders, though, we think ProHealth is the more convenient option because it comes with a scoop inside the container, whereas NOW instructs you to use whatever teaspoon you have handy. ProHealth’s powder is also less filmy-taste-forward, albeit cloudier when dissolved in water.

Before we get into the science of TMG and the logic behind our recommendations, consider this quick-reference chart comparing our top TMG supplements (the information is based on direct purchases through the brands’ websites and the label-recommended serving sizes):

TMG is trimethylglycine, also known as betaine. It’s a naturally occurring compound in animals (including humans), microorganisms, and plants. Common dietary sources include beets, spinach, wheat bran, wheat germ, dairy, eggs, chicken, and fish.15 Whether taken through food or supplements, it yields a similar bioavailability.16

In the body, TMG is both an osmolyte and a methyl group donor. As an osmolyte, it helps regulate the balance of water and salt in cells, so it’s essential for maintaining a stable cellular environment, allowing them to function as they should.12 As a methyl group donor, it readily gives up one or more of its methyl groups to other compounds in a process called methylation, which is integral to gene expression (by which the information encoded into a gene becomes a function).17

TMG’s role as a methyl group donor specifically relates to an amino acid called homocysteine. It’s normal to have some homocysteine in your blood, but elevated levels can cause health problems like coronary artery disease, heart attack, stroke, and cognitive decline.18 B vitamins can break homocysteine down into chemicals your body needs, but not effectively if you have a vitamin deficiency or a defect in the gene (MTHFR) responsible for processing the amino acid.19

TMG, however, also breaks down homocysteine — into the essential antioxidant amino acid methionine, necessary for making protein in your body and regulating metabolic processes20 21 — so it effectively rehabilitates a delinquent compound into a contributing member to your biochemistry.

Primary types and benefits of TMG supplements

On the supplements market, you’ll find TMG supplements in two forms: TMG hydrochloride (HCl) and TMG anhydrous.

The benefits of TMG HCl relate to digestive function. Attached to hydrochloric acid, the main component of stomach acid, its principal use is to raise stomach acid levels to help you break down protein, absorb nutrients from food, and control the levels of pathogens in your digestive tract — functions that are compromised in certain health conditions (atrophic gastritis or Helicobacter pylori infection) or with the use of acid-reducing medications (antacids, H2 receptor blockers, or proton pump inhibitors).22

TMG anhydrous, in contrast, is nonacidic. Think of it as TMG Classic, the fundamental form that functions as an osmolyte and methyl group donor. As such, it can benefit you primarily in these areas:

Theoretically, since homocysteine is also linked to cognitive decline, TMG supplementation should also have protective action against neurodegenerative disorders such as Alzheimer’s, but theory doesn’t quite play out in practice. For example, in 2001, a 24-week pilot study on Alzheimer’s patients ended up with variable results that couldn’t conclusively be interpreted to support TMG’s use as a cognitive protectant.31

More convincing is TMG’s potential to prevent or attenuate liver disorders, but even then the support is limited and would seem to involve very high doses (e.g., 10g per day) that are impractical from a supplementation standpoint and unsafe in terms of cardiovascular risk.32 33

Apart from the unknown side effect profile for people who are pregnant or breastfeeding, the biggest safety issue with TMG supplementation is the risk of elevated cholesterol.32 But the risk seems to present itself only with doses exceeding 4g per day.9 The label-recommended doses of our top-recommended TMG supplements are significantly lower than 4g, so you ought to be fine taking any of them — unless you already have a high or borderline-high lipid profile.

That’s without accounting for other ingredients in these supplements, which might carry separate risks. We discuss potentially concerning safety concerns of individual TMG supplements in their respective brand sections later on.

TMG HCl, however, may pose a risk to people with peptic ulcers. Because TMG HCl raises stomach acid levels, it could exacerbate ulcers or prevent their healing.43

As long as you’re not pregnant or lactating or have high cholesterol, a TMG supplement could be a sensible addition to your supplement regimen if you want to:

• Improve your physical strength performance
• Lower your cardiovascular risk (notwithstanding the previously mentioned risks)
• Extend your longevity in general

But don’t expect that taking TMG will automatically create these outcomes. By itself, TMG isn’t going to make you into some mega-muscled Methuselah. At best, it’s a support piece in an ecosystem of healthy living that includes exercise, a sensible diet, regular healthcare, and perhaps other supplements.

Also, despite claims to the contrary, you shouldn’t expect a TMG supplement to net you any appreciable benefits to your cognitive or liver health. Studies on TMG’s neuroprotective potential have been limited in scope and mixed in their findings, while its liver-protective effects require doses that are both higher than what you can reasonably get from a supplement and possibly harmful to your cardiovascular health.

What about TMG HCl?

TMG HCl serves a different function, so it’s best discussed separately.

This variant of TMG supplements is suited to people with indigestion stemming from insufficient production of hydrochloric acid, the main component of stomach acid. Called hypochlorhydria, this health condition is more common in older people, those with chronic stress, and patients who’ve undergone stomach surgery.22

Though supporting evidence exists for its ability to improve symptoms of hypochlorhydric indigestion, TMG HCl is more of a temporary relief protocol than a cure.44 Moreover, it isn’t an appropriate intervention for people with peptic ulcers, as the increase in stomach acid levels can irritate an ulcer or prevent it from healing. It’s also contraindicated for people taking medications for decreasing stomach acid, like proton pump inhibitors — they’re taking the medications for a reason, and TMG HCl could undo the benefits.43

Best single-ingredient TMG supplement

Every serving of NOW Sports Betaine powder delivers 1.6g of TMG anhydrous. With the label recommending two servings daily, you ideally end up taking 3.2g per day. Its dosage roughly aligns with clinical studies suggesting that doses of 2.5-4g are ideal for increasing strength performance and reducing cardiovascular risk.6 8 9 Its closest competitors in this guide deliver only 1g per day, so you’d need to take an off-label serving size to reach clinically effective levels. That’s why we selected NOW as the best single-ingredient TMG supplement.

It also gets decent marks for safety, as the NOW brand is well-known for high third-party testing standards, and the TMG in particular is certified to be vegan, non-GMO, and steroid-free (that last bit is good news for competitive lifters and other athletes who want to use the supplement for strength enhancement and are subject to drug testing). That being said, NOW falls short of being our safety pick for two reasons. The first is that its higher-than-others TMG dosage, on top of common dietary intakes, potentially skates close to the 4g daily threshold considered to be safe before TMG starts to pose a cardiovascular risk.10 9 The second is that NOW products are produced in a facility that processes allergen-containing ingredients. So while the TMG itself doesn’t include common allergens, it potentially contains traces of:

NOW also falls short in the convenience factor. For one thing, it’s a powder, which not only requires mixing (not conducive to on-the-go use) but also leaves a faint taste on the tongue. For another thing, it doesn’t include a scoop in the bottle, so you’ll need a separate half teaspoon or a sensitive kitchen scale to measure your doses. At least ProHealth, the other powder supplement in this guide, doesn’t overlook the user-friendly addition of a scoop.

Pricing, subscriptions, and refunds

NOW Sports Betaine Powder is our budget pick, too, because of its ultra-low per-serving cost. A single bottle through the NOW website costs $17.99 (before $6.95 shipping) and contains 106 servings, so every half teaspoon is equal to just $0.17. Likewise, it provides more TMG by weight than the other brands in this guide — $0.11 per gram. Life Extension is the only recommended competitor that competes with NOW in the cost field, but even that’s around three times as expensive on a per-serving/per-gram basis (approximately $0.33).

However, in two key cost-adjacent areas, NOW Sports fails to measure up to competitors. One is that it doesn’t offer direct subscriptions, so if you want a set-and-forget arrangement for your supplement, you’ll need to go through a third party such as iHerb.

The second issue is that NOW doesn’t offer a satisfaction guarantee. Therefore, if you’re thinking of returning your TMG (within the stipulated 30-day window), it has to be unopened. If you try the supplement and it doesn’t work out, you’ll have to eat the cost. Even third-party sellers may not honor your refund request if you try the product first.

Best TMG complex for longevity

ProHealth Longevity has cropped up a couple of times on our site, specifically in our guides to the best NMN supplements and best NAD+ supplements. The company’s NMN Pro Complete is particularly compelling because, in addition to TMG, it includes two other ingredients that are the subjects of numerous clinical studies and discussions on longevity:

• Nicotinamide mononucleotide (NMN): NMN is a precursor to nicotinamide adenine dinucleotide (NAD+) — that is, when you take NMN, it becomes NAD+ in your body. NAD+, for its part, is crucial for healthy mitochondrial function. Because mitochondria generate most of a cell’s energy, and cellular energy appears to play a role in longevity, the NMN-to-NAD+ conversion may be integral to a long and healthy life.34 35
• Trans-resveratrol: Trans-resveratrol — a type of antioxidant common in dietary sources such as berries, dark chocolate, and red wine — has demonstrated promise as a preventive of or treatment for a wide range of age-related pathologies, including cancer, neurodegeneration, cardiovascular disease, and muscle loss.36 37 38 39

ProHealth’s NMN Pro Complete supplement provides 1g of each ingredient listed above, which is either within or approximate to clinical ranges for longevity outcomes.37 40 The 500mg of TMG is lower, and a fraction of NOW’s dose, but also in line with amounts used in clinical studies to lower homocysteine levels.41 So, with NMN Pro Complete, you have an effectively dosed trifecta of well-studied ingredients that can both extend your life expectancy and improve your quality of life.

Importantly, TMG and NMN appear to have a synergistic relationship that can increase the efficiency of the NAD+ production process. NAD+ breaks down to form, among other things, nicotinamide (NAM), which the body recycles back into a generative pathway that forms new NAD+. But nicotinamide needs methyl donors like TMG to move along that pathway and eventually become NAD+. If you increase NAD+, you’ll get a concurrent increase in NAM, and if you don’t provide sufficient methyl donors to turn that NAM back into NAD+, it could potentially cause health problems instead of longevity solutions.42 Therefore, NMN Pro Complete has the potential to preserve and increase the efficiency of a process your body needs to thrive.

By the way, ProHealth Longevity NMN Pro Complete is available as either a powder or a capsule supplement. We prefer the powder because it’s a little easier to take (one scoop versus four capsules per serving) and costs a little less.

Pricing, subscriptions, and refunds

Longevity doesn’t come cheap, because ProHealth’s powder supplement will run you $109.80 as a one-time purchase and $76.86 as a subscription (30-, 60-, or 90-day delivery intervals) — the capsule supplement is more expensive, at $114 and $79.80, respectively. That’s around 8-11 times more than Life Extension, 4-6 times more than NOW, and two times more than Thorne.

ProHealth’s refund policy gives you 100 days to get your money back, but only if you haven’t opened the bottle. So, that’s 100 days to decide whether you regret your purchase, not to assess whether the supplement is to your liking. Compare that to Life Extension’s true satisfaction guarantee, which applies to opened products and lasts 365 days.

Best TMG supplement for digestive health

Even though it’s a TMG supplement, Thorne Betaine HCl & Pepsin isn’t formulated to increase longevity. Instead, it’s a digestive aid for people with low stomach acid levels. The “HCl” in its name refers to hydrochloric acid, the main component in your stomach for breaking down the food you eat. People who don’t produce enough hydrochloric acid in their stomach can experience symptoms of indigestion such as abdominal pain, bloating, gas, and diarrhea, so they might need exogenous HCl to keep their digestive system working properly.22

TMG HCl’s effect on stomach acid levels is rapid, with clinical subjects reaching a significantly lower gastric pH (higher acid) within minutes, but it lasts just over an hour.44 Therefore, it should be taken with every meal, as Thorne’s label instructs.

Thorne’s TMG supplement also contains pepsin, an enzyme necessary for digesting protein.45 Low hydrochloric acid levels correlate with protein maldigestion, which is why pepsin is often coadministered with TMG HCl.22 44

Every two-capsule serving of Thorne Betaine HCl & Pepsin provides 1g of the former and 47mg of the latter. While there’s no standard dose of pepsin, a 1g dose of TMG HCl is within the typical range used in treatment protocols (350mg to 3g).44 Because the label-recommended serving is closer to the median of the range, some users may need to start with a half dose.

Pricing, subscriptions, and refunds

Thorne Betaine HCl & Pepsin costs $47 per bottle as a one-time purchase. Although that’s the second-highest base price in this guide — around 2.6 times as much as NOW — Thorne has a relatively low per-serving cost owing to the large number of servings per bottle. If you take a full serving, it’s $0.42 per serving ($1.27 per day for three servings); if you take half servings, it’s $0.21 ($0.64 per day for three servings).

A subscription, though, knocks 10% off the base price, bringing it down to $42.30 ($0.19-$0.38 per serving, $0.56-$1.14 per day).

Of course, if you don’t eat three meals a day, the per-day costs will be lower.

And Thorne’s available subscription intervals are variable enough to accommodate individual usage needs, as you can choose to have your supplement delivered every:

• 2 weeks
• 1 month
• 45 days
• 2 months
• 3 months
• 4 months

If you aren’t satisfied with your supplement, you can write to Thorne within 60 days to request a refund. But keep in mind that Thorne doesn’t go so far as to call its refund policy a satisfaction guarantee; instead, it tells customers that it will do “[its] best to accommodate your situation,” which implies the possibility that your refund request could be rejected.

Safest and most accessible TMG supplement (lowest up-front cost, longest guarantee)

Life Extension TMG is our recommendation for the TMG-curious and other newcomers to longevity supplements. Besides its low base price (discussed in the next section), Life Extension provides a modest but clinically relevant 500mg-per-capsule dose that matches the amount you’d get from a serving of ProHealth.41 Plus, though a serving is two capsules, there are no other ingredients in it to complicate titrating up or down, so it’s more easily adjustable to your needs than ProHealth is.

Then there are the safety measures:

• Life Extension subjects both raw materials and finished products to third-party testing.
• The TMG, like all of the company’s supplements, is produced in an NSF-registered facility, which speaks to its compliance with rigorous health and safety standards.11
• The capsules are vegetable-based and gluten-free, so they’re good to go for vegetarians and people with a gluten intolerance.

On the flip side, Life Extension TMG isn’t as potent as its competitors since its dose is much lower than NOW’s and it’s absent the additional longevity-boosting ingredients of ProHealth.

Pricing, subscriptions, and refunds

Life Extension TMG is only $9.75 as a one-time purchase and $9 flat as a subscription. You could buy around 11 bottles for the price of one ProHealth, five for the price of one Thorne. Each bottle contains at least 30 label-recommend servings, so that’s $0.30-$0.33 per serving if you stick with Life Extension’s suggested protocol. (It drops or rises if you titrate, of course.)

With Life Extension, you also have the advantage of numerous subscription delivery intervals (1-12 months) and one of the best satisfaction guarantees in the industry (365 days). That’s a true guarantee, by the way — it applies to opened products — not like Thorne’s conditional guarantee.