Hey all, Welcome to another deep dive into supplements often flogged by supplement companies. Today we are going to be going to Betaine, what does, what it doesn't do and how good it is at doing it.
What is Betaine Anhydrous.
Betaine is a zwitterionic quaternary ammonium compound that is also known as trimethylglycine. Trimethylglycine is a methyl derivative of the amino acid Glycine, which are really fancy ways of saying its the same in structure as Glycine but with added methyl groups attached to it. The terms Betaine and trimethylglycine are used interchangeably but for the purpose of this write up I will refer to it as (TMG) from now on. Your body can naturally gain TMG from dietary sources, deriving it from choline which is found in many different foods.
What does it do.
TMG has several roles within the body depending on what is required of it.
The principal physiologic roles of TMG are as an osmolyte, methyl donor and activator of IGF-1 and a potential to increase lipolysis.
1) As an osmolyte TMG is shuttled into cells to protect against dehydration and stressors regulating cell hydration, swelling as well as cell wall strength [1,2,3] in this TMG is similar to Creatine.
2) The second is as a methyl donor, TMG has a few different groups that it can donate to all which have various effects.
Active Folate: Folic acid deficiency can be attenuated by TMG through pathways that are normally occupied by Folic Acid, the methyl donating process by TMG can act as a folate replacement. [4]
Homocysteine: This amino acid that your body gets from eating diets high in meat is a precursor to cardio vascular disfunction [5], TMG is able to donate a methyl group to it converting homocysteine to L-methionine a cardio and immunity protective amino acid [6,7]
S-Adenosyl Methionine: or SAM is increased from L-methionine from the afore mentioned methylation or directly from TMG. SAM is associated with decreasing fatty liver decease [8,9]
Now that we understand the primary functions of TMG lets get into the practicalities of what it can do for us and why it is included in pre workout supplements.
Speculation
The main mechanism of action that I am interested in a hypertrophic, strength and power context is the osmotic properties of TMG. The theoretic action of TMG is through the cell swelling by hyper hydrating it through fluid retention. This fluid retention makes the cells more durable to exercise induced stressors as well as potentially being able to stretch the muscle facia itself through this cell bloating pump... thats the theory, now the practical.
Muscle strength and power.
TMG supplementation on 14 men who had three months of prior training, so people new to the gym essentially found that after just 14 days a notable increase was noted [10,11] I don't rate this study particularly highly since its in newly trained individuals who will respond to resistance training regardless of their protocol.
A meta analysis done on 7 studies showed that only 2 of the studies showed any effect at all on power or strength [11]. The study dose highlight the need for further research due to the inconclusive nature of the currently conducted research.
However it is worth noting that both of these cases did not include the study of more experienced resistance trained individuals. Other studies have show the contrary, that resistance trained individuals benefit from TMG supplementation showing acute increases of power over 14 days os supplementation. [12,13,14]
When ever I see these kind of mixed results, especially in this context I have a habit of blaming the study set up for the mixed results. Regardless the information is inconclusive in relation to muscle strength and power.
Anecdotally over a 8 week supplementation period of 4g p/day 30 mins prior to resistance training in a 500 cal surplus during a new strength block meso cycle. noted strength increases over all my lifts. Most notable of which was my 3 rep max on deadlift that increased from 180kg to 205kg. The caveat of course is that this is anecdotal and I was in a surplus in calories.
Hypertrophy
A study I have previously linked [11] in untrained collage girls noted increased muscle thickness after 8 weeks of supplementation against the placebo, but this is misleading as the placebo group also increase muscle thickness by the same scale.
Another study on men partaking in CrossFit also saw no size difference against the placebo group, this is at 2.5g p/day [15]
Another study showed that 23 experienced resistance trained men had a statistically significant increase in arm size during a 6 week trail of 4g p/day [16]
Unfortunately I didn't do measurements prior supplementation during my 8 week test. Which was 20 weeks ago now. I did do a prior measurement that was 42.5cm (~16.5inches), my arms size 9 weeks into a cut are now 44cm (~17 inches). But I cannot even slightly tribute this to TMG as I've trialed several other supplements during this time.
Fat loss
A meta analysis revised six studies on the effect of TMG on body composition. The studies where run for a duration from 10 days to 24 weeks, so wildly different at dosages ranging from 2g to 10g, again wildly different. Of the 6 studies one found the participants actually gained weight during their testing period, though the participants did not engage in any exercise regime. the other 5 studies did show some benefit with a medium fat loss of 2.25kg(5lb). [17]
Another study looking at fatty liver disease noted that supplementing with TMG prevented fat build up on the liver, suggesting that it may be somewhat effective at lowing body fat [22]
There are a few money studies looking at fat oxidisation and lipolysis but they are all in animal studies which I wont delve into here as I want to focus on human trials.
As I ran TMG during a bulk phase I don't have any anecdotal evidence to add here.
Endurance
10 healthy males who where made to do exhaustive aerobic exercise while supplementing with 2.5g of TMG had no increase in aerobic capacity. [18] Though this paper looked at Choline levels, which as we know directly correlates to TMG in the body, found that after maximal endurance style training Choline levels where depleted, suggesting that this style of exercise has a demand of Choline has a metabolic substrate [19].
There is just no way near enough data on this to have any kind of conclusive statement on TMG's effectiveness, we sorely need more data here as there is potential for TMG to be effective.
IGF-1 Increase
TMG has been shown over and over again in animal studies to increase IGF-1 concentrations on blood plasma [20] and is often used as a feed supplement for that reason. I could only find one study that was done on humans, it tested 12 trained men taking 2.5g p/day. They took blood pre train and after a 2 week washout period and found that the group taking the TMG had much higher IGF-1 and much lower cortisol [21] which are both very important in building muscle. This could explain why we see some evidence for strength gain.
Dosing
Dosing has been see form as little as 0.5 to 10g in the research relating to physical activity which massively varying results, I usually like to push the envelop when it comes to supplements, however because the data pools are so small with TMG I personally have stuck to 4-5g p/day.
For performance output I wouldn't suggest going lower than 2.5g p/day.
Side Effects
Side effects that have recorded at these doses include:
-Potentially increases your risk of cardio vascular decease [22][23] though results are currently inconclusive.
-Stomach upset
The bottom line
The potential benefits of TMG are really pretty underwhelming, there are plenty of other supplements out there that do what TMG does but better, it seems to have some potential for positive outcomes in the gym but the evidence for me just isn't strong enough. Especially as the word is still out on relation to how it may effect cardio vascular health. At the end of the day I have about a months supply of the stuff left, when I reach the end of the bag I don't think I will be restocking.
I will take stock of the research in the coming years and reevaluate my position then, but until then it will be a mediocre performance supplement.
Parting Words
These write ups are being really well received which I am very grateful for, so thank you for the kind words. Next week I will either review monosodium phosphate, Phosphatidic Acid or if another is highly requested. In the mean time I am currently reading into the currently hyped Turkesterone, so will be releasing that in the coming months.
As always i'll happily answer any questions you may have!