GBB (Gamma-Butyrobetaine Ethyl Ester): Super Carnitine That Makes You Sweat?!

If you follow PricePlow, you have likely tried a carnitine-based supplement in the past. What if we told you that everything you’ve taken may pale compared to the new kid on the block, GBB?

The short goes like this: Not only will it leave you sweating more than anything on the market, it still provides the amazing general health benefits associated with carnitine supplementation. Dive into this post to find out if this carnitine precursor is on a path to dethroning the carnitine world as we know it!

TL;DR

GBB Supplements

GBB, or Gamma-Butyrobetaine ethyl ester HCl, is the molecule that your body converts into L-Carnitine when naturally producing its own carnitine.

Studies show that its supplementation can increase the body’s plasma L-Carnitine levels by nearly double! Thus, the benefits of GBB are similar to the benefits of carnitine supplementation – they depend on the user’s diet and carnitine status.

For some unknown reason (we have theories), GBB causes a serious amount of thermogenesis and sweating, especially if taken pre-workout, so it has been included in several new thermogenic fat burners.

The typical dose is 10-20mg twice daily, and right now the maximum we’d take is 50mg in a day.

Safety studies even include infants, and GBB is theorized to be safer than carnitine supplements at these doses because there’s no chance of it turning into toxic D-Carnitine, which could potentially be in some carnitine supplements.

Up-Front: What are the typical GBB “claims”?

Gamma Butyrobetaine

Can as little as 10mg of this bad boy make you work up a sweat faster? For some of us, the answer is very much yes

The purpose of this post is to educate and investigate the science on GBB, a relatively new soldier on the supplement ingredient chess board. Formally known as Gamma-Butyrobetaine ethyl ester HCl, GBB is an ingredient we see in newer fat-burners. While there are several claims made about the benefits of GBB, they have usually used it as a “sweat amplification” agent in products like RXS Radiate.

A few clinical trials that show GBB to be a formidable ingredient for the industry and certain types of dieters. The most impressive amongst these claims is a result that showed a near-doubling of plasma carnitine levels after supplementation, and an increase of 300% carnitine excretion.[1-2] In addition, it’s often advertised that GBB will function similarly to other carnitine supplements… but takes a step further due to its ability to raise plasma levels so incredibly high.

The recommended dosage of GBB sets it apart from other forms of carnitine supplements. While industry veterans like acetyl-l-carnitine (ALCAR) or l-carnitine-l-tartrate (LCLT) typically require doses closer to a gram, GBB works similarly to other forms of carnitine in far lower doses like 50mg per day.[3] This is a huge win for GBB, as high doses of other carnitine supplements take up too much space (disadvantageous in a capsule) and simply cost more.

Gamma Butyrobetaine Ethyl Ester HCl Plasma Carnitine

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]

“Super Carnitine”?

In past posts regarding GBB, we’ve called it “super carnitine”, as this is how several companies see the ingredient. It has clinical research backing its safety, it has a low active dose, and it raises carnitine levels in the body higher than other supplements. What’s NOT to love?

Seeing that nobody online has done any serious research on the ingredient, we dug up every scientific paper possible on GBB to see if these claims were true. Here’s what we came up with:

What is GBB?

Carnitine Biosynthesis Pathway

The Carnitine Biosynthesis Pathway.[28] GBB, or γBB, is circled in red.

Gamma-butyrobetaine eventually gets converted into l-carnitine. Through an enzyme known as Gamma-butyrobetaine dioxygenase (or BBD[28]), GBB is converted to L-carnitine. “GB dioxygenase”, as the name implies, is an oxidoreductase enzyme,[4] and these enzymes facilitate conversions through electron movement. By supplementing with GBB, you provide a “push” for the body to produce more L-Carnitine. Think of GBB like lumber set aside to build a house. More lumber equals more house!

To understand why it “pushes” the body to produce more L-carnitine, get ready for some basic general chemistry lessons. Chemical reactions tend to behave according to Le Chatelier’s principle. Le Chatelier’s principle is a law of equilibrium[5] — the body wants to maintain balance.

The GBB / L-Carnitine Equilibrium

If you add more GBB, you will get more carnitine until the “levels” of both product and reagent balance out. Likewise, if we have more product, enzymes can facilitate the breakdown of product into its constituent parts: more reagents. This allows the body to do its best to never have too much of any one thing. Due note that while it is never quite this simple in nature, it’s the easiest way to think of such reactions.

GBB Carnitine

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

GBB supplementation likely works based on this principle. We add so much material to the left that the reaction goes to the right. It creates more carnitine to balance out the ratio of GBB and l-carnitine in the body. Tyrosine supplementation and even prohormones also work by helping conversion reactions go towards the right. It may be easier to just refer to GBB as “pro-carnitine”.

The enzyme for GBB conversion to carnitine is commonly found in the kidney, liver, and the brain.[6,7] Given the roles of the kidney and liver in fat metabolism, having GBB dioxygenase in these organs makes sense. Carnitine serves an essential role in fat metabolism that will be discussed more below.

To break out of textbook mode, let’s describe the mechanism as simply as we can: you put more on the left, you get more on the right. If you put more on the right, you get more from the left.

A Brush Up on Carnitine Itself

Carnitine is the molecule that facilitates movements of fatty acids during beta-oxidation, the process that lets us get energy from fats. It’s easy to visualize carnitine as a “fatty acid taxi cab” that takes the fatty acids to different spots within the mitochondria (the powerhouse of the cell).[8] Keto dieters should especially understand the situation well: once the fatty acids are dropped off by carnitine, they are converted into ATP through beta-oxidation. This process is going on constantly throughout the day but elevates during intensive exercise as fatty acids are burned for fuel.

Carnitine Function in Intracellular Transport

Carnitine’s Function in Intracellular Transport.[28] Note how important this molecule is if you plan on delivering fatty acids to cells. You can ignore the bottom yeast section.

Thus, it may make sense to take some before a workout: more taxis going to the destination means more guests will arrive, correct?

This is where GBB should kick in. By providing enough GBB, we allow the body to “push” the conversion reaction to the right, which means we get more carnitine. If we have more carnitine, we can transport more fatty acids into the mitochondria to burn as fuel. That’s the idea, anyway.

Does More Carnitine Actually Do Anything?

Let’s finally get to the crux of our pursuit: does GBB supplementation really do anything? We’re going to first tackle the benefits of carnitine supplementation before getting into the nitty gritty with the unique claims attached to GBB itself. The short answer is that carnitine has several benefits it can impart through proper supplementation, especially in those that are deficient. Carnitine is likely best known for improving brain health, as it improves focus, memory formation, and even the ability of the brain to resist disease or degradation.[9-11]

Vegan? Vegetarian? Aging? Then read up

But again, carnitine really shines for fat loss in those that are deficient. Vegans, vegetarians, and boomers should all consider giving carnitine a shot as supplementation is associated with improved fat oxidation (through its natural mechanism) and even enhanced intra-set recovery.[12] It may even help the deficient hold on to muscle mass more efficiently as these demographics age.[13,14]

Carnitine

Any form of carnitine is a good idea for vegans

In terms of general health, more carnitine is a good thing. Carnitine has been long-used to improve sperm quality on top of being a potent antioxidant.[15,19] It helps keep glucose levels down in the body while improving insulin sensitivity.[16] It may even be worth trying when treating symptoms of autism and ADHD![17-18]

The carnitine deficiency downfall

…And those benefits are only the most clear. There’s an uncountable number of things that can go wrong when your body cannot mobilize fat due to a carnitine deficiency, so there’s nearly as many things that it may improve in some form if you’re hampered by such a deficiency. So it’s tough to make claims about how it will specifically help you, it’s just easy to say that “being carnitine deficient is a bad thing”.

So yes, GBB will probably do something through virtue of improving creatinine levels in the blood. Carnitine itself is a very well studied compound, the only difference with GBB is the method of increment and the weight of the dose. While we lose out on the versatility of other forms of carnitine, like acetyl l-carnitine’s ability to cross the blood-brain barrier, we make up for it with a lower and more tolerable dose with some additional “fringe” benefits.

Current Research on GBB-Exclusive Health Benefits, Superiority,  and Safety

Whenever a new supplement storms onto the scene, we go directly to studies that advocate for its safety. There have been far too many instances of new ingredients turning out to be ticking time-bombs.

In this matter, we will not lie — GBB took us by surprise. They studied GBB in human infants and determined GBB to be safe to take. Given that infants may be the most sensitive test subjects around, we can safely say GBB supplementation is probably safe for adults,[2] although we’d always welcome more toxicology research.

Safer due to no D-Carnitine?

In fact, some GBB manufacturers claim that GBB is likely safer than normal carnitine! While that must be taken with a grain of salt since they’re selling the ingredient, they present a sound argument: In short, the problem is that carnitine supplements may contain the D-carnitine enantiomer of L-carnitine.[3] D-carnitine is toxic in humans and mammals,[20] as it may reduce your body’s stores of carnitine and induce a deficiency!![26,27]

GBB can claim superiority in a few other realms beyond safety. Science has associated l-carnitine supplementation with gastric distress in high doses.[22-24] Anecdotal reviews concur. Since the dose of GBB is often much lower than other forms, it likely can circumvent this unfortunate side effect. Carnitine suffers from a poor bioavailability as the body may use only 18% of the dose.[21] While we have seen little data on the bioavailability of oral GBB, we’re hoping it’s better than 18%!

GBB leads to nitric oxide enhancement

Gamma Butyrobetaine Ethyl Ester Nitric Oxide

GBB elevates nitric oxide levels, but researchers don’t understand the entire pathway yet![25]

The first unique aspect of GBB is its consistent impact on nitric oxide levels. [25] At least a few studies have showed GBB to be a potent vasodilator. As workout fiends who are always down for enriched blood flow, we love nitric oxide boosters at PricePlow. By improving blood flow, GBB will probably help get nutrients to damaged muscle and joint tissue at a more rapid rate. It may even help keep blood pressure down. GBB has been more consistent in terms of vasodilation than other forms of carnitine. [25]

A sweaty situation!

Secondarily, GBB will make you sweat like a damned sweat factory. This is often the main selling point (such as in products like “Super Sauna”), as some of us absolutely love to sweat when training. Truth be told, we’ve seen no direct science on why this may occur, but for some individuals, it’s hilariously effective at doing so…. to the point of some of our discussion forum regulars being annoyed by it.

Gamma Butyrobetaine Ethyl Ester HCl Carnitine Excretion

While the carnitine levels doubled from GBB, the excretion was 30x higher, meaning there’s all kinds of carnitine turnover with GBB![1]

We can not find any real science on why this is occurring. One postulation of ours (with zero basis) is that the chemical reaction to get from GBB to Carnitine is exothermic (releases heat), and by triggering the reaction en masse via supplementation, it theoretically outputs the heat. If we stumble upon an explanation that’s based in actual science, we will update this article. Until then, we’ll leave this article at “it’s hot and makes most people sweat more for some reason”.

So if that’s not enough for the more conservative-minded folks who need to know every mechanism about every ingredient they take, then they may need to wait until more research is done.

GBB Dosage

Right now, the standard dosage seems to be 10-20mg twice per day, or 25mg in one shot. Lower doses will likely still yield benefits, they just may not be “felt”, while higher doses may work but may induce too much of the heated for too many individuals.

For this reason we aren’t going over 50mg per day right now.

Featured Supplements with GBB inside

Radiate Fat Burner

The Radiate Fat Burner lives up to its name!

A favorite with this ingredient is RXS Supplements Radiate. It contains several other ingredients, many of which are also geared towards thermogenesis, if you couldn’t tell by the name!

Conclusion

PricePlow loves carnitine – especially the right kind for the right consumer. No, we don’t think it’s a miracle supplement, and it’s not always for everyone all the time, but we definitely enjoy it.

Well, one of our favorite supplement categories has just gotten a whole lot more interesting.

GBB is a worthy addition to the “carnitine wars”, as it has its place in products – especially capsule-based thermogenic fat burners – that use it over ALCAR or LCLT. For those that suffer gastric distress from other forms of carnitine, GBB may be the way to go. For those that hate taking a ton of powder or pills, GBB is the way to go.

However, ALCAR should still be better than GBB for cognitive benefits due to its ability to cross the blood-brain barrier, and LCLT has some other androgenic workout benefits. But in terms of carnitine production for vegans, vegetarians, meat-haters, the aging, and keto-dieters, we’re thinking GBB may be superior to LCLT or straight L-carnitine.

So, is GBB worth it? Depending on the situation, we think it’s at least worth trying. We always encourage you to make sure you do your research (several citations are below) and pick the form of carnitine that best serves your individual needs.

And if you do choose to use a supplement with GBB inside, don’t forget your towel, because you just might be one of the lucky ones who gets the sweat amplification effect.

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References

  1. Charles J. Rebouche, E. Peter Bosch, Catherine A. Chenard, Kay J. Schabold, Steven E. Nelson; “Utilization of Dietary Precursors for Carnitine Synthesis in Human Adults”; The Journal of Nutrition, Volume 119, Issue 12, 1 December 1989, Pages 1907–1913; https://academic.oup.com/jn/article-abstract/119/12/1907/4738183
  2. Ann Louise Olson, Charles J. Rebouche; “γ-Butyrobetaine Hydroxylase Activity is Not Rate Limiting for Carnitine Biosynthesis in the Human Infant”; The Journal of Nutrition, Volume 117, Issue 6, 1 June 1987, Pages 1024–1031; https://academic.oup.com/jn/article-abstract/117/6/1024/4768474
  3. Sheen, A. (2016, May 10). LeanGBB® replacement of L-Carnitine. Retrieved from https://www.slideshare.net/AlexSheen3/leangbb-replacement-of-lcarnitine
  4. Paul HS, Sekas G, Adibi SA (Feb 1992). “Carnitine biosynthesis in hepatic peroxisomes. Demonstration of gamma-butyrobetaine hydroxylase activity”. European Journal of Biochemistry / FEBS. 203 (3): 599–605. doi:10.1111/j.1432-1033.1992.tb16589.x. PMID 1735445; https://www.ncbi.nlm.nih.gov/pubmed/1735445
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  7. Lindstedt G, Lindstedt S, Nordin I (Oct 1982). “Gamma-butyrobetaine hydroxylase in human kidney”. Scandinavian Journal of Clinical and Laboratory Investigation; https://www.ncbi.nlm.nih.gov/pubmed/7156861
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  9. Goo, M, et al; “Protective effects of acetyl-L-carnitine on neurodegenarative changes in chronic cerebral ischemia models and learning-memory impairment in aged rats”; Arch Pharm Res; 2012 Jan; 35(1):145-54; https://www.ncbi.nlm.nih.gov/pubmed/22297753
  10. Carta A, Calvani M, Bravi D, Bhuachalla SN; “Acetyl-L-carnitine and Alzheimer’s disease: pharmacological considerations beyond the cholinergic sphere”; Ann N Y Acad Sci. 1993; 695:324-326; https://www.ncbi.nlm.nih.gov/pubmed/8239306
  11. Gomez L.A., Heath S.D., Hagen T.M. “Acetyl-L-carnitine supplementation reverses the age-related decline in carnitine palmitoyltransferase 1 (CPT1) activity in interfibrillar mitochondria without changing the L-carnitine content in the rat heart”; Mechanics of Aging Development; 2012 Feb-Mar; 133(0): 99–106; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147858/
  12. Hongu, N, et. al; “Carnitine and choline supplementation with exercise alter carnitine profiles, biochemical markers of fat metabolism and serum leptin concentration in healthy women“; The Journal of Nutrition; January 2003; https://www.ncbi.nlm.nih.gov/pubmed/12514272
  13. Pistone G, Marino A, Leotta C, Dell’Arte S, Finocchiaro G, Malaguarnera M. Levocarnitine administration in elderly subjects with rapid muscle fatigue: effect on body composition, lipid profile and fatigue. Drugs & aging. 2003; 20(10):761-7; https://www.ncbi.nlm.nih.gov/pubmed/12875611
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  15. Balercia G, Regoli F, Armeni T, Koverech A, Mantero F, Boscaro M. Placebo-controlled double-blind randomized trial on the use of L-carnitine, L-acetylcarnitine, or combined L-carnitine and L-acetylcarnitine in men with idiopathic asthenozoospermia. Fertility and sterility. 2005; 84(3):662-71; https://www.ncbi.nlm.nih.gov/pubmed/16169400
  16. Ruggenenti P, Cattaneo D, Loriga G, et al. Ameliorating hypertension and insulin resistance in subjects at increased cardiovascular risk: effects of acetyl-L-carnitine therapy. Hypertension (Dallas, Tex. : 1979). 2009; 54(3):567-74; https://www.ncbi.nlm.nih.gov/pubmed/16169400
  17. Van Oudheusden LJ, Scholte HR. Efficacy of carnitine in the treatment of children with attention-deficit hyperactivity disorder. Prostaglandins, leukotrienes, and essential fatty acids. 2002; 67(1):33-8; https://www.ncbi.nlm.nih.gov/pubmed/12213433
  18. Geier DA, Kern JK, Davis G, et al. A prospective double-blind, randomized clinical trial of levocarnitine to treat autism spectrum disorders. Medical science monitor : international medical journal of experimental and clinical research. 2011; 17(6):PI15-23; https://www.ncbi.nlm.nih.gov/pubmed/16169400
  19. Cao Y, Qu HJ, Li P, Wang CB, Wang LX, Han ZW. Single dose administration of L-carnitine improves antioxidant activities in healthy subjects. The Tohoku journal of experimental medicine. 2011; 224(3):209-13; https://www.ncbi.nlm.nih.gov/pubmed/21701126
  20. Harmeyer, J. (2002). “THE PHYSIOLOGICAL ROLE OF L-CARNITINE”; http://lohmann-information.de/content/l_i_27_article_3.pdf
  21. Evans AM, Fornasini G. Pharmacokinetics of L-carnitine. Clinical pharmacokinetics. 2003; 42(11):941-67; https://www.ncbi.nlm.nih.gov/pubmed/12908852
  22. Rebouche CJ. Carnitine. In: Modern Nutrition in Health and Disease, 9th Edition (edited by Shils ME, Olson JA, Shike M, Ross, AC). Lippincott Williams and Wilkins, New York, 1999, pp. 505-12; https://www.scribd.com/doc/221145295/27915730-Modern-nutrition-in-Health-and-Disease-9th-ed-pdf
  23. The editors. Carnitine: lessons from one hundred years of research. Ann NY Acad Sci 2004;1033:ix-xi; https://nyaspubs.onlinelibrary.wiley.com/doi/pdf/10.1196/annals.1320.019
  24. National Research Council. Food and Nutrition Board. Recommended Dietary Allowances, 10th Edition. National Academy Press, Washington, DC, 1989; https://www.nap.edu/catalog/1349/recommended-dietary-allowances-10th-edition
  25. Sjakste, N., Kleschyov, A. L., Boucher, J., Baumane, L., Dzintare, M., Meirena, D., . . . Kalvinsh, I. (2004). Endothelium- and nitric oxide-dependent vasorelaxing activities of gamma-butyrobetaine esters: Possible link to the antiischemic activities of mildronate. European Journal of Pharmacology, 495(1), 67-73. doi:10.1016/j.ejphar.2004.05.006; https://www.ncbi.nlm.nih.gov/pubmed/15219822
  26. Rebouche, CJ; “Effect of dietary carnitine isomers and gamma-butyrobetaine on L-carnitine biosynthesis and metabolism in the rat”; The Journal of Nutrition; 1983 Oct; 113(10):1906-13; https://www.ncbi.nlm.nih.gov/pubmed/6619971
  27. Rebouche CJ, Engel AG; “Carnitine metabolism and deficiency syndromes”; Mayo Clinic Proceedings; 1983 Aug; 58(8):533-40; https://www.ncbi.nlm.nih.gov/pubmed/6348429
  28. Strijbis K, Vaz F, Distel B; “Enzymology of the carnitine biosynthesis pathway”; IUBMB Life; 2010 May; 62(5):357-62; https://www.ncbi.nlm.nih.gov/pubmed/20306513
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