Phosphatidic acid

Geschatte leestijd: 9 minutenPhosphatidic acid is a substance closely involved in muscle protein synthesis. This substance can be supplemented, and the question that now arises is: does it work? Does supplementation of phosphatidic acid lead to more muscle growth? To answer this question, I delved into the literature. I discuss these studies in this article so that you can form your own opinion about the effectiveness of this supplement. But first, an explanation of what phosphatidic acid exactly is.

Table of Contents

• What is phosphatidic acid?
• The effect of phosphatidic acid on body composition and muscle strength
• Study 1: Hoffman et al. 2012
• Study 2: Joy et al. 2014
• Study 3: Escalante et al. 2016
• Study 4: Andre et al. 2016
• Study 5: Gonzalez et al. 2017
  • Conclusion

What is phosphatidic acid?

Gradually, scientific research is unraveling what causes muscle cells to grow on a molecular scale. Factors such as nutrition and training result in a complex interplay of molecules that regulate the process of muscle growth. One important player in this process is a protein complex called mechanistic target of rapamycin complex 1 (mTORC1). This protein complex integrates stimuli such as growth factors (e.g., insulin), energy availability (e.g., glycogen), availability of amino acids, and mechanical stimuli provided by weightlifting in the gym [1]. It is therefore considered a very important regulator of muscle growth.

To some extent, it can be said that mTORC1 “adds up” all these stimuli, in response to which it induces muscle cells to increase muscle protein synthesis and thus ultimately allows the muscle cell to grow: muscle hypertrophy.

mTORC1 is regulated by numerous molecules. One of these molecules is phosphatidic acid. When you train in the gym, your muscle cells will increase the production of phosphatidic acid due to the mechanical forces on these cells. The produced phosphatidic acid is then able to activate mTORC1 [2]. But what is phosphatidic acid exactly? Phosphatidic acid is a lipid; a fatty substance. Chemically, it closely resembles the fat stored in your fat cells, triacylglycerols (also known as triglycerides). Triacylglycerols consist of three fatty acid chains and a glycerol molecule that holds them together. Phosphatidic acid is a diacylglycerol. Instead of three fatty acids, it contains only two. In the place where the third fatty acid chain is normally present, as in triacylglycerol, phosphatidic acid has a phosphate group. This phosphate group gives it certain properties that make the molecule suitable for, among other things, intracellular signaling (including that of muscle growth). Phosphatidic acid also serves as the precursor to many other lipid-like substances found in cell membranes.

So, what researchers wondered was the following: If exercising causes your muscles to grow, and this growth is – at least in part – the result of increased production of phosphatidic acid; would it also make your muscles grow if you take phosphatidic acid as a dietary supplement? There is actually only one way to find out. You entice some athletes to participate in a study and divide them into two groups: one group receives phosphatidic acid supplementation and the other group receives a placebo. Then, you measure some things in both groups at the beginning, such as body composition and muscle strength. After that, you let both groups train for several weeks while both groups take their supplement (phosphatidic acid or placebo). At the end of the study, you perform the same measurements again. With the help of some statistics, you can then determine whether the supplement has worked by comparing the results between the phosphatidic acid group and the placebo group.

The effect of phosphatidic acid on body composition and muscle strength

So far, five studies have been published comparing phosphatidic acid with a placebo to determine its effect on muscle growth and strength [3]. The studies have a lot in common in terms of design. They are all placebo-controlled, allowing them to prove whether the supplement works better than a placebo. Also, all studies included men with prior experience in strength training, and supplementation was combined with a strength training program. Moreover, four out of the five studies examined the effect on body composition and strength of the upper body, and all studies looked at the effect on lower body strength.

Below in the table, you can find a summary of the results of these five studies (the study by Andre et al. had two phosphatidic acid groups, which are listed separately):

Abbreviations: 1-RM, 1-repetition maximum; BP, bench press; SQ, squat; LP, leg press; LBM, lean body mass; FM, fat mass. Results marked with an * indicate statistical significance, meaning that the observed difference is likely not due to chance.

Study 1: Hoffman et al. 2012

The first study, published in 2012 by Hoffman et al., was small-scale with only sixteen participants in total [4]. Seven of them were supplemented with phosphatidic acid (750 mg per day) and the remaining nine received a placebo. Subsequently, the men underwent an eight-week strength training program.

In the table, it can be seen that the 1-RM bench press and 1-RM squat showed a slight advantage over placebo. Also, lean body mass, determined by dual-energy x-ray absorptiometry (DXA), increased more than in the placebo group. However, you shouldn’t expect too much from this: the placebo group saw virtually no increase in lean body mass (+0.1 kg) after 8 weeks of strength training. In any case, none of these results were statistically significant, so they could also be due to chance.

It can be argued that the lack of a statistically significant effect may be a type II error, or false negative. There were few participants, making it difficult to achieve statistically significant differences. When a different statistical method than usual was used (magnitude-based inference instead of analysis of variance), it was concluded that phosphatidic acid supplementation had a very likely positive effect on lean/dry body mass.

Finally, it should be noted that the study was sponsored by Chemi Nutra, which holds a patent on phosphatidic acid supplementation for muscle growth and strength increase [9]. Two of the authors of the paper are also registered as inventors on this patent and were paid by Chemi Nutra.

Study 2: Joy et al. 2014

A follow-up study was conducted by Joy et al. with 28 participants this time [5]. Although there was a smaller increase in lean body mass compared to placebo than in the earlier study by Hoffman et al. (+1.2 kg vs +1.6 kg), this increase was statistically significant this time. A significantly greater increase in lower body strength (determined by 1-RM leg press) compared to placebo was also found. Furthermore, ultrasound was used to assess the cross-sectional area of the rectus femoris (part of the quadriceps). Here too, a significantly greater increase was found in the phosphatidic acid group compared to the placebo group. Taken together with the increase in lean body mass, this is a strong indication that muscle mass has increased. And although upper body strength did increase, it did not reach statistical significance. The authors also note a trend towards more fat mass loss in the phosphatidic acid group.

In this study too, the same conflict of interest played a role; sponsorship by Chemi Nutra and the same two authors being paid by this company. The last author, Jacob M Wilson, also does not have an unblemished reputation in the literature on dietary supplements. A recent study from his group, in which HMB supplementation combined with ATP led to stunning results [10], has been heavily criticized on social media, but also in the scientific community [11, 12, 13].

Study 3: Escalante et al. 2016

Another study whose results align with those of Joy et al. is that of Escalante et al. [6]. A major problem with this study is that the phosphatidic acid supplement was combined with other ingredients, namely vitamin D, beta-hydroxy-beta-methylbutyric acid (HMB), and leucine. Therefore, it is actually impossible to say to what extent the positive results found in this study were due to phosphatidic acid. The addition of these ingredients was not arbitrary: the ingredients belonged to the dietary supplement MaxxTOR produced by Max Muscle Sports Nutrition. They sponsored the study, along with Chemi Nutra.

Study 4: Andre et al. 2016

The study by Andre et al. published last year deviated from the other studies in the dosage used [7]. Instead of 750 mg per day, the participants received 250 mg or 375 mg. So there were three groups in this study: a placebo group, a group receiving 250 mg of phosphatidic acid, and a group receiving 375 mg of phosphatidic acid. What immediately stands out in this study is the enormous strength gain achieved by the 250 mg group with the 1-RM leg press compared to the placebo group: +42.4 kg! However, this was not statistically significant, indicating that the study was extremely underpowered: too few participants to distinguish this large effect from chance.

The 375 mg group gained about half of that compared to the placebo group, namely ‘only’ 20.5 kg. So a lower dosage seems to work better. And that’s quite strange. Because why would that be..? What is also remarkable is that the lean mass increased by 1.1 kg and 0.3 kg less than in the placebo group in the groups receiving 250 mg and 375 mg, respectively. And then the authors – based on magnitude-based inference – write that the 375 mg group experienced a possible positive effect on lean mass and the 250 mg group a likely positive effect. How is that possible..? So they gain less lean mass than the placebo group, and yet that’s a positive effect on lean mass..? And there are more inconsistencies in this publication regarding the results of the groups. Finally, this study was also sponsored by Chemi Nutra.

Study 5: Gonzalez et al. 2017

To my great joy, another study was published this year by Adam Gonzalez of Hofstra University [8]. This study is the first not sponsored by the industry. Once again, participants with experience in strength training (n=15) were involved, they followed a strength training program three times a week for eight weeks, this time looking at 1-RM squats, deadlifts, and bench presses, and muscle thickness of the rectus femoris, vastus lateralis, biceps brachii, and triceps brachii was determined by ultrasonography. Unfortunately, no assessment of body composition was made. As shown in the table, virtually no difference was found in bench press (+0.5 kg vs. placebo), squats (+0.6 kg vs. placebo), and also deadlifts (+2.6 kg vs. placebo). There were also no significant changes in muscle thicknesses (+0, +0.29, -0.17, and +0.31 cm vs. placebo for the rectus femoris, vastus lateralis, biceps brachii, and triceps brachii, respectively). If phosphatidic acid had an effect, it was apparently very small.

Conclusion

Phosphatidic acid is closely involved in the regulation of muscle growth. For this reason, researchers have investigated whether supplementation of this substance further promotes muscle growth and strength when combined with strength training.

A total of five studies have been published on this topic. One of these five studies supplemented phosphatidic acid along with other substances that could have an influence, so no conclusions can be drawn about the effect of phosphatidic acid in this case. Of the remaining four studies, one found a significant effect on muscle strength and lean body mass. Another study seems to indicate a trend towards an improvement in lean body mass, and another towards an improvement in muscle strength. It should be noted that these studies were all sponsored by the supplement industry. A final study, without conflicting interests, found absolutely no effect. This does not necessarily mean that the other studies were fraudulent, despite the similarities between the studies. As always, there were also some subtle differences between the studies.

Nevertheless, this makes it very difficult to say whether it works or not. However, if you set aside those objections, it seems that phosphatidic acid works.

References

1. Bond, Peter. “Regulation of mTORC1 by growth factors, energy status, amino acids and mechanical stimuli at a glance.” Journal of the International Society of Sports Nutrition1 (2016): 8.
2. O’Neil, Tyriina K., et al. “The role of phosphoinositide 3‐kinase and phosphatidic acid in the regulation of mammalian target of rapamycin following eccentric contractions.” The Journal of physiology14 (2009): 3691-3701.
3. Bond, Peter. “Phosphatidic acid: biosynthesis, pharmacokinetics, mechanisms of action and effect on strength and body composition in resistance-trained individuals.” Nutrition & metabolism1 (2017): 12.
4. Hoffman, Jay R., et al. “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 Nutrition1 (2012): 47.
5. Joy, Jordan M., et al. “Phosphatidic acid enhances mTOR signaling and resistance exercise induced hypertrophy.” Nutrition & metabolism1 (2014): 29.
6. Escalante, Guillermo, et al. “The effects of phosphatidic acid supplementation on strength, body composition, muscular endurance, power, agility, and vertical jump in resistance trained men.” Journal of the International Society of Sports Nutrition1 (2016): 24.
7. Andre, Thomas L., et al. “Eight weeks of phosphatidic acid supplementation in conjunction with resistance training does not differentially affect body composition and muscle strength in resistance-trained men.” Journal of sports science & medicine 3 (2016): 532.
8. Gonzalez, Adam M., et al. “Effects of phosphatidic acid supplementation on muscle thickness and strength in resistance-trained men.” Applied Physiology, Nutrition, and Metabolism4 (2017): 443-448.
9. De Ferra, Lorenzo, et al. “Method for increasing muscle mass and strength.” S. Patent Application No. 13/373,649.
10. Lowery, Ryan P., et al. “Interaction of beta-hydroxy-beta-methylbutyrate free acid and adenosine triphosphate on muscle mass, strength, and power in resistance trained individuals.” The Journal of Strength & Conditioning Research7 (2016): 1843-1854.
11. Hyde, Parker N., Kristina L. Kendall, and Richard A. LaFountain. “Interaction of Beta-Hydroxy-Beta-Methylbutyrate Free Acid and Adenosine Triphosphate on Muscle Mass, Strength, and Power in Resistance-Trained Individuals.” The Journal of Strength & Conditioning Research10 (2016): e10-e11.
12. Phillips, Stuart M., et al. “Changes in Body Composition and Performance With Supplemental HMB‐FA+ ATP.” The Journal of Strength & Conditioning Research5 (2017): e71-e72.
13. Gentles, Jeremy A., Phillips, Stuart M. “Discrepancies in publications related to HMB-FA and ATP supplementation.” Nutrition & Metabolism1 (2017): 42.