ProGBB: The Gamma Butyrobetaine Supplement that Enhances Carnitine

SYNMR’s ProGBB is a well-tested form of the carnitine-booster Gamma Butyrobetaine Ethyl Ester, more easily known as GBB

Carnitine supplements are some of the most popular ones around. If you follow PricePlow, you’ve likely tried at least one, and that’s a good thing, because way too many people are carnitine deficient due to our society’s irrational fear of red meat. Without sufficient carnitine, we have a difficult time with an immense number of biological processes, ranging from fat loss to cognitive function to muscle recovery.

But if you want to get some of the benefits of an increased carnitine store without taking grams of the substance, GBB is here to help. Beyond its ability to increase carnitine levels, GBB is interesting because it causes added thermogenesis and sweat when exercising with it! So on top of every benefit that comes with carnitine supplementation, GBB provides an interesting feature that many love to train with.

There’s one form of GBB we’ve seen lab tests on: ProGBB by SYNMR Biotechnologies (ProGBB.com), the focus of this article.

Watch our YouTube video about GBB

If you don’t feel like reading, you can also watch me explain GBB below:

The Quick and Dirty: What’s ProGBB Do?

While its full name is Gamma-Butyrobetaine ethyl ester HCl, we’ll refer to it as GBB to keep things simple. You may have seen ProGBB thrown into many of the fat burners and pre workouts, such as Merica Labz Napalm Red White & Boom, a hybrid fat burning pre workout supplement.

Companies often include it in products as a “sweat amplification” agent, as that’s the interesting effect of the supplement, but it’s the improved carnitine status that we feel bring the actual benefits.

GBB Supplements add to the “carnitine pool” by increasing the reagent — GBB (or γBB in the image) — which goes on to make more carnitine if your body needs it!

Because of this, it’s powers extend far beyond the sweat factor. Clinical trials show that GBB (and thus ProGBB) may be a formidable ingredient that certain dieters can benefit from — namely, those who aren’t eating enough meat, the elderly, or intensely training athletes. The most impressive claim from these studies is a near-doubling of plasma carnitine levels after supplementation. These studies also show a 300% increase in carnitine excretion with quite large doses,^[1,2] which means the levels are absolutely getting increased in the system.

Companies use the above carnitine-boosting data to advertise GBB as a carnitine-like product that functions akin to ingredients like acetyl L-carnitine (ALCAR) or L-carnitine-L-tartrate (LCLT), but outside of the interesting benefit of thermogenesis, there’s also another benefit: lower dose! While the aforementioned ALCAR and LCLT have effective doses in the ~500mg-2g range (which can take anywhere from 1-4 large capsules), ProGBB works in doses as low as 50mg per day.

Given that increased carnitine status may help with cognitive focus,^[3] we feel that ProGBB can and should expand to greater areas than just dieting, and wouldn’t mind seeing it in nootropic supplements that simply don’t have room for full doses of ALCAR.

GBB is naturally a part of our carnitine production process… when we take it… we get more carnitine and its effects!

What IS ProGBB?

Gamma-butyrobetaine (GBB – you may also see it as γ-butyrobetaine in research) is an intermediate that the body converts to L-carnitine through the enzyme Gamma-butyrobetaine dioxygenase (BBD).^[4] For a quick biochemistry lesson, dioxygenase enzymes work by transferring electrons from a “donor” to an “acceptor”. This enzyme forms carnitine from GBB by shuffling electrons from “donor” compounds.^[5] The reaction adds a hydroxyl group to our GBB molecule to form carnitine.

Long story short – Supplementing GBB gives you more carnitine building blocks! GBB is the lumber and carnitine is the house — more lumber means more house!

This is a two way process. Remember, the body loves homeostasis.

The pathway image above is more detailed, but the point is that your body will do its best to maintain hemeostasis and can go in both directions

In the above image, the arrows in the above diagram go in both directions. To understand why more substrate is a good idea, it’s helpful to review inorganic chemistry. Chemical reactions behave according to Le Chatelier’s principle — which is a law of equilibrium.^[6] If you add in more GBB, the reaction will go to the “right” until the concentrations of reagent and product balance out. Likewise, if you have more carnitine than GBB, the body will produce GBB from the carnitine to maintain a stable balance. It’s never this simple in nature, but this is the best way to visualize this step.

The Carnitine Biosynthesis Pathway.^[3] GBB, or γBB, is circled in red.

This reaction takes place in the kidney, liver, and brain. These tissues possess the BBD enzyme required for carnitine synthesis.^[7,8] The kidney and liver play essential roles in fat metabolism so their BBD concentration makes sense.

Meanwhile, consumption of carnitine (via meat or supplementation) is also broken down into trimethylamine and GBB by bacteria in the gut microbiome,^[9] so the process is a two-way street.

To summarize: if you have more of the stuff on the left, you get more of the stuff on the right. If you have more of the stuff on the right, you get more of the stuff on the left.

“Super Saiyan Carnitine”

We sometimes call ProGBB “super-carnitine” in some of our supplement reviews and analysis blog posts. We do this as it’s a great description of GBB! It’s a pro-carnitine ingredient with research backing its efficacy, it has a low active dose, and it boosts carnitine levels in the body more than many carnitine products. There’s little reason to not consider it super carnitine. It made us think GBB could be too good to be true, so we dove into the literature discussed above and below.

An early study on carnitine’s precursors showed that GBB (to the right) is the best of the bunch at increasing plasma carnitine levels.^[1]

Why Do We Care About Carnitine?

Carnitine facilitates movements of fatty acids through the mitochondria during beta-oxidation, the metabolic process that converts fat into usable energy. We like to think of carnitine as the “fatty acid airport shuttle” for the cell.^[10] Once the fatty acids are “dropped off” by carnitine, they continue along the beta oxidation pathway and ultimately become ATP, which energy to the cell. This process goes on throughout the day, but the body revs up beta-oxidation during exercise.

“L-carnitine function. l-carnitine shuttles long-chain fatty acids inside the mitochondria by forming a long chain acetylcarnitine ester. The complex is then transported into the mitochondrial matrix by carnitine palmitoyltransferase I (CPT I) and carnitine palmitoyltransferase II (CPT II). The fatty acids are then broken down through the process of β-oxidation to deliver the 2-carbon molecules to the Krebs cycle, leading to the generation of energy under the form of adenosine triphosphate (ATP). In addition, by binding an acetyl group, l-carnitine can maintain the levels of Acetyl-CoA and coenzyme A, playing its buffering role.”

This exercise induced increase in fat shuttling highlights a potential use of ProGBB — more shuttles can get more fat to the airport. By taking ProGBB, we’re increasing the amount of carnitine that our body can use for fat transport — so we can burn more for energy when we need it. Note that this is a rough postulation of just one potential ProGBB use – carnitine does a ton more than shuttle fatty acids.

Does More Carnitine Do Anything?

Let’s get to the entire point of this article: will taking ProGBB and creating more carnitine do anything for us? Before we get into those unique benefits of GBB, we’ll discuss the benefits of carnitine supplementation itself, since that is effectively a proxy for what we’re doing here.

The short answer is that yes, carnitine supplementation has benefit – but most especially in those that are deficient. For instance, carnitine, mostly in its ALCAR incarnation, is best known as a brain health boosting agent, as it may improve focus, memory formation, and neurodegenerative resistance.^[11-13].

Humans are ancestrally meat-eaters, and meat contains high amounts of carnitine. It’s often more interesting to look at what goes wrong when we remove carnitine due to dietary exclusion or age.

Vegans? Vegetarians? Aging Populations?

Due to their lack of intake, vegans, vegetarians, and aging adults are all likely to be deficient in carnitine. For those that are deficient, carnitine supplementation may improve fat oxidation and may even combat muscular atrophy because of aging.^[14-16] While heavy meat eaters may not experience as many of these additional benefits (their carnitine pools are already high), Americans have been fooled into eating less red meat, and can now be considered generally deficient.

Carnitine’s Function in Intracellular Transport.^[17] Note how important this molecule is if you plan on delivering fatty acids to cells. You can ignore the bottom yeast section.

For this reason, we don’t consider carnitine to be a “fat burner”, but an ingredient that can bring you back to baseline. Consider it similar to something like Vitamin D: if you get plenty of sunshine, you shouldn’t need much more and won’t see a ton of added benefits from taking more. But if you’re deficient, taking a good supplement will fix a ton of issues caused by the deficiency.

With ProGBB, we’re supplementing around a non-optimal diet, and since its dose is so small, weight loss supplement formulators can skew to the side of “carnitine caution” by including it.

General Health Benefits

While “general health” is the boring section of our articles, the benefits of carnitine supplementation (and thus ProGBB by proxy) are of note. There is evidence showing Carnitine may act as a potent antioxidant agent.^[18] It also may improve everything from sperm quality to insulin sensitivity.^[19,20] There’s even literature showing that carnitine may help mitigate the symptoms of autism and ADHD.^[4,21]

These benefits are the most obvious attached to carnitine supplementation. However, there is an infinite amount of things that can go wrong if the body cannot oxidize fat because of carnitine deficiency. Carnitine supplementation may be more of a “better safe than sorry” recommendation — as a tiny dose will do well to starve off any symptoms associated with carnitine deficiency in at-risk populations.

So yes, ProGBB will do something because of its ability to increase our body’s carnitine reservoir, and that has major implications on our overall health.

While the carnitine levels doubled from GBB, the excretion was 30x higher, meaning there’s all kinds of carnitine turnover with GBB!

Is GBB Safe? Does GBB Do Anything Else? How Much Should I take?

The first step towards reviewing a new ingredient is a dive into the toxicity literature. The current state of the literature shows that GBB may be safe. One study even gave GBB to human babies without adverse side effects.^[2] Babies respond to toxic substances more dramatically than adults, so we’ll take this as a “cautious green light”. We’d of course love more human-based research, but when you have babies safely receiving something, that’s a good sign for adults.

The D-Carnitine Angle: Could GBB be safer than Carnitine?

Companies that manufacture gamma butyrobetaine claim that GBB is likely safer than other forms of carnitine supplementation. While these companies are admittedly trying to sell you something, the argument they’re making has weight to it.

This study found freakin D-Carnitine heavily dosed in one supplement. Whose was it? We’ll probably never know. But it could be avoided with third-party lab testing, simply eating more meat, or having your body create the carnitine itself… with GBB.

Reason being, carnitine products may be unintentionally “contaminated” with an enantiomer of L-carnitine called D-carnitine^[22] — which is toxic in humans and mammals. Perhaps ironically, D-carnitine reduces carnitine in the body and may cause symptoms of carnitine deficiency.^[23,24]

When taking GBB, your body creates carnitine the way it was meant to, and that means nearly exclusively L-Carnitine, which animals only synthesize and respond physiologically to.^[25] By taking ProGBB, you’re effectively trusting your body’s carnitine synthesis machinery more than that of an unknown manufacturer whose carnitine likely has no published third-party lab tests.

Note that there are a few exceptions to the rule above, as some forms of bacteria create the D-form, but we only require the L-form and do not want to get the D-form in our supplements!

The GI-Issue and Absorption Angle

L-carnitine supplementation causes gastric distress in high doses.^[26-28] Since ProGBB has a much lower dose, and supplementing GBB puts the body in control of carnitine synthesis, GBB may actually be a preferable form of supplementation for those that have stomach issues! Meanwhile, L-Carnitine is infamous as a poorly bioavailable compound when ingested orally. The body may actually use only 18% of what you take… at most.^[29]

While there is little data on the bioavailability of GBB, we’re hoping it’s not as bad, and given the large increases in carnitine excretion that have been recorded, we’re confident it’s working.

Other ProGBB Benefits

GBB elevates nitric oxide levels, but researchers don’t understand the entire pathway yet!^[30]

Now, we’ll tackle some other things that ProGBB does that set it apart from its carnitine-supplement siblings. The first unique quality is GBB’s ability to act as a potent vasodilator via modulation of nitric oxide levels.^[30] Since the staff at PricePlow is always excited about the benefits of increased NO, this may be our favorite unsung secondary benefit of ProGBB supplementation.

For those new to workout “pump” ingredients, vasodilators dilate blood vessels and allow for heightened blood flow throughout the body. Besides improving nutrient delivery to cells, vasodilators also lower blood pressure by giving the blood more room to play. GBB appears to be more consistent vasodilator than other forms of carnitine.^[30]

The sweat factor

ProGBB seems to make many users perspire far more than normal. This is often the main selling point of the ingredient, as many dieters seem to “feel like they’re getting a better workout” when sweating.

We haven’t seen direct science that explains the mechanism, but one postulation we offer is that the chemical reaction that produces carnitine from GBB may be exothermic, thus releasing energy in the form of heat upon its reaction. A simpler explanation could be that all forms of added carnitine increase energy release, simply due to their enabling of increased fatty acid transport. An even wilder hypothesis: perhaps the effects of GBB consumption are similar to the “meat sweats” that many get when eating high amounts of meat (this is usually blamed on protein, which has a high thermic effect).

If we stumble upon an explanation based on clinical science, we’ll update this article and look out for comments below. Until then, just know that ProGBB may make you sweat like crazy.

GBB Dosing

We’d recommend beginners sticking to two daily doses of 10-25mg per dose. Low doses will still bring the sweat hard but may not be as noticeable as higher doses. We don’t have enough data on this ingredient to recommend doses higher than 50mg total per day, but we’ve anecdotally heard of some users using twice that amount!

However, it should be noted that the study performed on infants used “500 µM γ-butyrobetaine”,^[2] and 500 micromolar = 0.0005 moles, and given the molar mass of 146.2074 g/mol for GBB, this means that even the infants were given 73mg! We don’t ever suggest this on a child, but the point is that humans can tolerate more than 50mg… yet the sweat effect seems to be pronounced already there.

In the other study, this happened at very high doses:

Participant 12 received 75 mg “y-butyrobetaine/(kg body wt-d). The solid inner salt was dissolved in fruit juice or carbonated beverage and consumed in two equal amounts daily at breakfast and dinner. Because participant 12 complained of excessive sweating and salivation 1-3 h after ingestion of the -y-butyrobetaine supplement, the dosage was reduced to 37.5 mg/(kg body wt-d) for participants 13-16. Only one of these subjects reported any unusual effects (mild increase in sweating on d 11-13) with that dosage of the supplement.^[1]

Needless to say, we don’t suggest such astronomical doses, and it’s interesting to see the research paper even discuss the subject who complained of excessive sweat and salivation!

Staying Safe – Where Should We Buy GBB?

If you have give GBB a try, we highly recommend seeking a reliable manufacturer. Our preferred recommendation are the team at SNYMR, due to their release of several lab tests and ease of contact. They title their trademarked take on GBB as ProGBB, which we’ve discussed throughout this document.

While consumers may not be able to get ProGBB from the supplier directly, this is the form of GBB we’ve seen the most data on:

ProGBB Lab Tests and Documentation

The following four PDFs tell an interesting story:

Interesting: Collect enough GBB (which we don’t recommend taking at once), and you do get calories. This has been proven for amino acids like BCAAs too.

• ProGBB Specifications
• ProGBB COA (Certificate of Analysis)
• ProGBB Energy Testing
• ProGBB TSCA Testing

From the documents above, we learn unique bits of information such as the fact that large amounts of GBB has calories (it goes without saying that we’d never take so much as to get any level of usable caloric energy from it).

Additionally, large doses did not cause rat toxicity, but in unreasonably high doses, they do. All of the doses tested are well beyond what is ever used in human supplements, so we do not have concerns with the standard 25-50mg dosing strategy.

Brands looking to use this ingredient can get in touch with them at SYNMR.com or ProGBB.com.They also produce a potent Eria Jarensis extract they backed up with extensive testing results.

Conclusion: ProGBB Brings the Heat

We love carnitine — especially for those in need. We realize it is not a cure-all or a magic tonic, but we enjoy using it, especially when meat is low or workout difficulty is high. GBB is a worthy contender for the throne of carnitine products. It’s affordable, doesn’t take up much serving size real estate, and it revs up carnitine levels. For those that suffer from GI issues or just hate taking massive serving sizes, ProGBB is the next to try.

SYNMR Biotechnology is the manufacturer of ProGBB and supported this article, its research, and the lab tests

However, ALCAR is still a great option for those seeking cognitive benefits because of its ability to cross the blood-brain barrier. However, we think ProGBB may be the best choice for the general population, especially in these “sweat amplification” products and weight loss capsules.

Once again, ProGBB will work best in those deficient in carnitine — vegans, vegetarians, the aging, and those that just hate meat. Which, sadly, is a rapidly growing segment of the population that’s clearly in need of supplemental help.

If you DO choose to use ProGBB, don’t forget your towel…. you’ll thank us when you cover the gym in sweat.