Occasionally I’ll browse the bodybuilding periodicals, staying abreast of current research and the latest muscle building supplement hype. In so doing, I was recently surprised by ‘Muscular Development’ taking a look back and citing a phosphatidic acid-L-leucine combo as a top supplement research discovery of 2016. Not because I presently hold a strong opinion on the efficacy of combining these; I’ve not personally tried it as of this writing. It’s because I’d thought the hype of phosphatidic acid, and the possibility of it working synergistically with L-leucine, was all the rage in 2014-2015.
Oh well, time flies for everyone I guess. Or maybe muscle building research just moves more slowly than that of other ‘industries.’
However, since Muscular Development regards this ingredient stack as a breakthrough of ‘creatine proportions’, let’s take a closer look at the research and possibilities.
And because ‘MaxxTOR’ appears to be the preeminent product containing the PA-Leucine combo, let’s call this the ‘does Maxtor work’ question.
It’s all about mTOR
The mechanistic target of rapamycin (mTOR) is a protein kinase enzyme that acts as a regulator of protein synthesis, cell proliferation, cell motility, cell survival, autophagy, and transcription. In a nutshell, mTOR is the executive in charge; the enzyme directing the components of cellular growth and proliferation. This puts it at obvious importance for strength and muscle hypertrophy.
Notably, it also makes its inhibition important in some cancer treatments. But that’s a different topic.
Resistance exercise stimulates mTOR to do its signaling, thus triggering protein synthesis.
Long periods of frequent training appear to down-regulate mTOR, making muscle growth more difficult as weeks of workouts accumulate without a break.
Specific supplements have been shown to enhance the mTOR signaling pathway. One such supplement is the amino acid L-arginine. Another is the amino acid L-leucine. And one with a different and very interesting route of enhancing mTOR is phosphatidic acid (PA).
PA is a phospholipid and a major component of cell membranes. During eccentric contraction of muscle, sarcomeres begin hydrolizing phosphatidylcholine into PA. The PA then signals mTOR, which stimulates muscle protein synthesis. So PA exists endogenously and is released in response to weight training. But it can also be taken as a supplement.
Since amino acids and PA each stimulate mTOR through different mechanisms, an obvious assumption is that they’ll work synergistically, thus providing more muscle growth when combined or “stacked.”
This is where the ‘does MaxxTOR work’ question takes shape.
Leucine for Muscle Growth (as mTOR activator)
So how does leucine activate mTOR?
Despite pseudo erudition to the contrary, nobody’s identified the exact mechanism by which L-leucine activates mTOR. If researchers aren’t even sure how it occurs, it’s difficult to interpret descriptions by laymen feigning understanding of the topic.
The best explanation I’ve encountered is one by Layne Norton in this article. In his analogy, Norton describes protein synthesis as the construction of a skyscraper. With that image in mind, mTOR is the general contractor, the company directing the project. The skyscraper being built represents the protein being synthesized. Bulldozers, cranes, and other machinery used to construct the building represent cellular components of protein synthesis. And leucine is the ‘cash’ the contracting company has available for infusion into the project to build it fast and efficiently.
PA + Leucine for Muscle Growth
Assuming accuracy of Norton’s analogy with L-leucine, where might PA fall into the picture? It activates mTOR via a route independent of leucine. Maybe it could therefore be considered an infusion of cash or resources to the contracting company itself, giving it additional tools to build the skyscraper. If that’s the case, it could work synergistically with leucine, producing a result greater than the sum of its parts. But it could just as easily work separately or even antagonistically.
Each of these supplements have been shown to benefit muscle building on its own. An eight week human study done by Hoffman et al showed that PA has a positive effect. Seven weight trained men given 750 mg of PA per day experienced an average of 12.7% increase in squat strength and a 2.6% increase in LBM compared to nine men in a control group receiving a placebo.
Same goes for leucine. Numerous studies have revealed its role in stimulating muscle protein synthesis. One such study done on 36 men and women (age 65-75) showed supplementing with it can increase muscle size and strength in older people without adding any physical training.
The way I see it, there are three possibilities in combining them.
- They work synergistically, combining to create a better post-workout muscle recuperative effect than either ingredient by itself.
- Each supplement works but not synergistically, possibly resulting in one’s effect outweighing that of the other.
- They thwart each other’s positive effect, causing the combination to have negative effects compared to the effect of either supplement by itself.
That third possibility has been discussed by bloggers citing a rodent study done on the combination of leucine and PA. Actually, the study was done to discover if there’s an effect on anabolism when combining PA with whey protein concentrate (WPC). This is befitting since many strength athletes and bodybuilders get a majority of their leucine from whey protein.
PA and Whey Protein in Rats
Scientists wanted to find out if oral PA ingestion would acutely increase “anabolic signaling markers” and muscle protein synthesis (MPS). More specifically, they were out to discover whether there was a difference between MPS from dietary PA, with and without whey protein concentrate (WPC).
The researchers divided 18-hour-fasted male Wistar rats into four groups. One group was a control that only received water. Another group received soy-derived PA only. A third group received WPC only. And a fourth group received WPC + PA. There was no physical training added to the experiment.
Three hours post feeding, the animal’s gastrocnemius (calf) muscles were removed for analysis of Akt-mTOR signaling, muscle mass regulation and metabolism through gene expression, and muscle protein synthesis (MPS).
The findings were surprising. While some components of Akt-mTOR signaling had increased most in the WPC + PA group, protein synthesis was lower in that group compared to the rats that received only the PA and those that received only the WPC. Protein synthesis at 3-hours post ingestion was significantly higher in the PA group compared to the control group. It was most elevated in the WPC group compared to control.
With more questions raised than answered by this study, its ultimate purpose appears to be to promote further studies. The research team points out a major limitation as the “limited post-feeding time point interrogation”, adding a possible related explanation as follows…
“Combined PA and WPC may alter the mTOR pathway activation dynamics relative to WPC-induced mTOR activation and, thus, peak MPS levels are shifted to the right or left of the 3-hour post-feeding sampling point.”
Bottom line: There’s a lot more to inter-workout protein accretion than the peak level MPS might hit at the three hour marker after a meal. This is only one of a few shortcomings of the study, along with no physical training added to the mix.
‘Does MaxxTOR Work’ given Additional Ingredients?
The Maxxtor product has two additional ingredients besides its leucine and phosphatidic acid. Its producers have apparently thrown in some Beta-Hydroxy-Beta-Methylbutyrate (HMB) and vitamin D for good measure.
HMB is a metabolite of leucine. One human study showed that it might induce acute muscle anabolism, “albeit a different route than leucine”, the study’s researchers concluded. Sounds like a natural addition for a proprietary ingredient combo.
Vitamin D was probably added due to a French study showing it enhances the anabolic effect of leucine. The researchers there discovered that higher levels of vitamin D basically stimulate muscle cells to produce more insulin receptors, thus revving the anabolic engine for the reception of leucine.
Experimenting with PA + Leucine
As always, I’m not making a recommendation; just reporting the supplement and training scene as I see it and giving feedback on my personal trials and results. I’ll keep reporting on what I think is personally making me ‘strong with age’, and what’s not.
I’m currently testing a PA-Leucine supplement (not Maxxtor). I don’t want to pay for extra ingredients given I haven’t (thus far) been impressed with HMB and I already get ample doses of vitamin D. Strict recording of training feedback will reveal whether adding this combo gives me a recuperation bump. I’ll report my results in the comment section.
Feel free to comment with any feedback you have on PA or the PA-Leucine stack.
- Jay R Hoffman, Jeffrey R Stout, David R Williams, Adam J Wells, Maren S Fragala, Gerald T Mangine, Adam M Gonzalez, Nadia S Emerson, William P McCormack, Tyler C Scanlon, Martin Purpura, Ralf Jäger. ‘Efficacy of phosphatidic acid ingestion on lean body mass, muscle thickness and strength gains in resistance-trained men.’ Journal of the International Society of Sports Nutrition (9:47 DOI: 10.1186/1550-2783-9-47) Oct. 2012
- Layne Norton, PhD. ‘The Anabolic Trigger: Learn More about Leucine’ com (Supplementation) Nov. 2013
- T Ispoglou, H White, T Preston, S McElhone, J McKenna, and K Hind. ‘Double-blind, placebo-controlled pilot trial of L-Leucine-enriched amino-acid mixtures on body composition and physical performance in men and women aged 65–75 years.’ European Journal of Clinical Nutrition (70, 182–188; doi:10.1038/ejcn.2015.91) June 2015
- Brooks Mobley, Troy A. Hornberger, Carlton D. Fox, James C. Healy, Brian S. Ferguson, Ryan P. Lowery, Rachel M. McNally, Christopher M. Lockwood, Jeffrey R. Stout, Andreas N. Kavazis, Jacob M. Wilson, and Michael D. Roberts. ‘Effects of oral phosphatidic acid feeding with or without whey protein on muscle protein synthesis and anabolic signaling in rodent skeletal muscle.’ Journal of the International Society of Sports Nutrition (DOI: 10.1186/s12970-015-0094-7) Aug. 2015
- Wilkinson DJ, Hossain T, Hill DS, Phillips BE, Crossland H, Williams J, Loughna P, Churchward-Venne TA, Breen L, Phillips SM, Etheridge T, Rathmacher JA, Smith K, Szewczyk NJ, Atherton PJ. ‘Effects of leucine and its metabolite β-hydroxy-β-methylbutyrate on human skeletal muscle protein metabolism.’ The Journal of Physiology (Volume 591, Issue 11, Pages 2911–2923) April 2013
- Salles J, Chanet A, Giraudet C, Patrac V, Pierre P, Jourdan M, Luiking YC, Verlaan S, Migné C, Boirie Y, Walrand S. ‘1,25(OH)2-vitamin D3 enhances the stimulating effect of leucine and insulin on protein synthesis rate through Akt/PKB and mTOR mediated pathways in murine C2C12 skeletal myotubes.’ Molecular Nutrition (Volume 57, Issue 12, Pages 2137–2146) Dec. 2013