Supplements

Phosphatidic Acid

Updated · 25 sources

Phosphatidic acid (PA) is a phospholipid, a type of fat molecule found in every cell membrane. It is sold as a soy-derived dietary supplement, with the claim that it switches on mTOR (mechanistic target of rapamycin), a protein that controls muscle growth signaling. Most trials used a branded ingredient called Mediator.

The mTOR link comes from cell and rodent experiments on PA made inside muscle cells. Whether a capsule does the same thing is a separate question. Human evidence comes from six small studies with 121 men in total, most of them funded by supplement companies. Results conflict, a 2022 scoping review concluded the evidence does not support PA for performance or body composition, and the one human study we found that took muscle biopsies reported lower, not higher, anabolic signaling after PA than after placebo in older men.

This page summarizes what the cell studies, animal studies and clinical trials report. It is for education only and is not medical advice.

Property Detail
Type Phospholipid; dietary supplement ingredient
Supplement source Soy-derived; the main tested ingredient is Mediator (Chemi Nutra)
Route Oral capsule
Doses in cited trials 250–750 mg/day for 8 weeks; a single 750 mg split over 1 hour in the acute study
Claimed mechanism mTOR activation; shown in cells and rodents, not shown after oral dosing in people
Human muscle evidence 6 small studies, 121 men, no women; no meta-analysis found
Half-life Not established; kinetic data are limited to one person and one small study
US status Sold as a dietary supplement; FDA does not approve supplements before sale
WADA status Not named on the 2026 Prohibited List

What it is

PA has a glycerol backbone with two fatty acids and one phosphate group attached. In the body it is a precursor for membrane phospholipids and triglycerides, and it also acts as a signaling molecule (Bond, Nutr Metab 2017). It makes up only a small share of total cell phospholipid (Hoffman et al., JISSN 2012).

Food supplies little of it. In a survey of 38 foods and 3 herbs, cabbage leaves were among the richest foods at 700 nmol/g, and animal foods contained under 60 nmol/g (Tanaka et al., J Agric Food Chem 2012). Bond converts the cabbage figure to about 0.5 mg/g and calls dietary amounts negligible next to the doses used in supplement trials.

Supplements use a concentrate, so the capsule weight and the PA dose can differ. The grade used in the acute human study, Mediator 50P, was 50–60% PA, with the rest made up of other phospholipids. In that study, 1,500 mg of product provided about 750 mg of PA (Smeuninx et al., Clin Nutr 2019).

For a related lipid sold for memory and cortisol claims, see Phosphatidylserine.

How it works in the body

PA made inside muscle cells

This is where the mTOR idea comes from, and nearly all of it is from cells and rodents:

  • Cell culture. In mammalian cells, growth signals raised cellular PA through the enzyme phospholipase D. PA bound the same region of mTOR that rapamycin targets, and this was needed to activate mTOR’s downstream targets (Fang et al., Science 2001).
  • Stretched muscle. Passive stretch of skeletal muscle ex vivo raised PA and mTOR signaling, and blocking phospholipase D prevented both (Hornberger et al., PNAS 2006).
  • A later correction, in mice. Using knockout mice, the same research group later found that the enzyme diacylglycerol kinase ζ, not phospholipase D, drives the rise in PA after mechanical loading (You et al., J Biol Chem 2014).

So PA appears to be part of how loading turns into a growth signal in rodent muscle. That does not show that swallowing PA adds to the signal.

PA added from outside the cell

Adding PA to the medium of cultured cells does raise mTOR signaling. In C2C12 mouse muscle cells at 10–30 µM, soy PA raised a marker of mTOR activity by about 636–658%, and egg PA by about 206–221%. Soy lysophosphatidic acid (LPA) and soy phosphatidylserine also raised it (Joy et al., Nutr Metab 2014). Bond notes that in cells, PA species with unsaturated fatty acids were active and saturated ones were not.

How outside PA works is disputed. One cell study found it does not act by binding mTOR directly. Instead, it is converted to LPA, which activates a cell-surface receptor and the ERK pathway. That study also found that leucine and PA signal through parallel pathways (Winter et al., Am J Physiol Cell Physiol 2010).

What happens after a capsule

Oral PA does not reach the blood intact. Digestive phospholipases break it down in the gut, the fragments are absorbed and rebuilt in intestinal cells, and the products travel in chylomicrons (fat-carrying particles) through the lymph. Bond states that how much PA reaches muscle is unclear.

Human kinetic data are minimal:

  • One-person poster. After 1.5 g of soy PA, plasma PA peaked at 3 hours, about 32% above a baseline of 2.66 nmol/mL, and was still raised at 7 hours. That is a peak of about 3 µM, while cell studies have used 10–100 µM (Joy et al.; Bond).
  • Acute study in 8 older men on PA. After about 750 mg split over 1 hour, plasma PA was raised from 180 to 300 minutes after exercise, about 2- to 3-fold (Smeuninx et al.).

These two results differ in size. They come from one person versus a small group, with different doses, timing and exercise conditions, so neither gives a reliable half-life.

Regulatory status

PA is sold in the US as a dietary supplement. FDA does not have the authority to approve supplements for safety and effectiveness before they are sold (FDA 101: Dietary Supplements). A search of FDA’s GRAS (generally recognized as safe) notice inventory for “phosphatidic” returned no records on November 8, 2026 (FDA GRAS Notice Inventory). GRAS notices are voluntary, so a missing notice does not show that an ingredient is unsafe. It means only that no notice is on file under that search term.

PA is not named on the WADA 2026 Prohibited List.

What the research shows

Resistance-training trials

All five training trials enrolled resistance-trained young men and ran for 8 weeks. Each compared supplement plus training with placebo plus training. Changes below are pre-to-post, supplement vs placebo:

Study Participants Daily dose Lean mass Lower-body strength Group difference by standard test
Hoffman et al. 2012 16 men (7 PA, 9 placebo); unsupervised training 750 mg PA +1.7 vs +0.1 kg Squat +12.7% vs +9.3% Not significant (lean mass p = 0.065)
Joy et al. 2014 28 men; supervised training 750 mg PA +2.4 vs +1.2 kg Leg press +51.9 vs +32.4 kg Significant (lean mass p = 0.01; leg press p under 0.05)
Andre et al. 2016 28 men (9 on 250 mg, 9 on 375 mg, 10 placebo); supervised 250 or 375 mg PA +0.5 kg (250 mg), +1.3 kg (375 mg) vs +1.6 kg Leg press +20.1% (250 mg), +13.4% (375 mg) vs +8.9% Not significant (lean mass p = 0.55; strength p = 0.58)
Gonzalez et al. 2017 15 men; supervised 750 mg PA Total body composition not assessed Squat +8.4% vs +8.1%; deadlift +10.1% vs +8.9% Not significant (squat p = 0.79; deadlift p = 0.66)
Escalante et al. 2016 18 men (8 supplement, 10 placebo) 750 mg PA plus leucine, HMB and vitamin D3 +1.9 vs +0.8 kg Leg press +58.3 vs +29.1 kg Significant, but for the blend

Four points help in reading this table:

  • Only one PA-alone trial reached significance. That was Joy et al. Bond’s 2017 review makes the same point and adds that the trials were small enough to miss a small effect.
  • Escalante cannot isolate PA. The product also contained HMB and leucine, both of which are studied for muscle in their own right. Thigh muscle mass, fat mass, power and jump did not differ between groups. The paper also reports the lean-mass result inconsistently: p under 0.001 in the abstract and p = 0.041 in the results.
  • Gonzalez measured muscle directly and found no effect. Ultrasound muscle thickness did not differ in any of four muscles. For example, rectus femoris grew 3.6% vs 3.2%, and biceps grew 3.7% vs 9.6%.
  • Andre’s placebo group gained the most lean mass. Neither dose differed from placebo on standard testing, which is what the paper’s title says. Its abstract nonetheless concludes that a benefit is “likely.”

“Likely” benefit claims. Hoffman and Andre found no significant group differences, then used “magnitude-based inference” (MBI) to report likely benefits. A statistical reanalysis found that at small-to-moderate sample sizes, MBI raises the false-positive rate to two to six times that of standard testing, and concluded it “should not be used” (Sainani, Med Sci Sports Exerc 2018). Hoffman’s own power for group differences was only 0.05–0.46.

Reading the Joy abstract. The abstract lists +2.4 kg lean mass, +1.0 cm cross-sectional area and +51.9 kg leg press “over placebo.” The results show these were the PA group’s own gains. Placebo gained 1.2 kg, 0.6 cm² and 32.4 kg, so the between-group differences were about 1.2 kg, 0.4 cm² and 19.5 kg. Bench press did not differ between groups (p = 0.11).

Post-workout protein was standardized in some trials: Hoffman gave a 36 g amino acid and collagen blend, and Joy gave 24 g of hydrolyzed collagen, chosen because it is low in leucine. None of these trials was designed to compare PA with whey protein or creatine, or to test it on top of them.

Mechanistic human data

The only study we found that looked inside human muscle after oral PA points the other way. Smeuninx et al. randomized 16 men aged 65–75 in a single-blind, parallel design to about 750 mg of soy PA or rice-flour placebo after one-leg resistance exercise, with muscle biopsies and a stable-isotope tracer:

Measure in the exercised leg Placebo PA
Myofibrillar protein synthesis, 150–300 min Rose above basal (P = 0.001) No rise (P = 0.83)
Protein synthesis, 0–300 min About 40% above basal (P = 0.023) No rise
p70S6K, rpS6, 4E-BP1 and Akt signaling, 150–300 min Rose above basal Significantly lower than placebo (P under 0.01)

The direct placebo vs PA comparison of protein synthesis over 150–300 minutes narrowly missed significance (P = 0.051). The authors concluded that acute PA appears to interfere with the anabolic response in older men and may not be viable for sarcopenia.

This result has limits. It was a single dose in small groups of older men, and the authors say longer-term supplementation still needs study. It does not directly test younger men or 8 weeks of use. None of the 8-week training trials measured mTOR signaling, as Andre et al. point out, so we found no human study showing that oral PA raises it.

Animal data

In fasted rats, a single oral PA dose raised mTOR and rpS6 phosphorylation at 3 hours. Muscle protein synthesis only trended upward vs control (p = 0.08). Protein synthesis was lower with PA plus whey than with whey alone, even though the signaling markers were high, and the authors suggested PA may delay whey’s effect (Mobley et al., JISSN 2015). The authors of the human biopsy study suggest species differences may explain why their findings differ.

Reviews and meta-analyses

We found no meta-analysis of PA for muscle. The closest reviews are:

  • Teixeira et al. 2022. A systematic search through August 2020 found six studies, five in adult men and one in older men, too few for more than a scoping review. Three suggested no effect on lean mass and the others a possible benefit, including one that used a multi-ingredient product. The authors concluded that the evidence does not support PA for performance or body composition in young or older men (Teixeira et al., J Sports Sci 2022).
  • Valenzuela et al. 2019. This review graded PA as evidence level B, meaning mixed or unclear (Valenzuela et al., Eur J Nutr 2019).
  • ISSN 2018. The International Society of Sports Nutrition listed PA under “limited or mixed evidence,” while placing creatine monohydrate and protein in its “strong evidence” group (Kerksick et al., JISSN 2018).

Our PubMed and Europe PMC searches on November 8, 2026 found no later randomized muscle trial. A University of São Paulo trial (estimated 45 men; 375 or 750 mg/day vs placebo for 8 weeks) was registered with estimated completion at the end of 2021. Its registry status is “unknown,” and we found no published results (NCT04277364).

Who paid for the research

Study Disclosed funding and ties
Hoffman 2012 Chemi Nutra grant; two authors were paid Chemi Nutra consultants and named inventors on its pending patents
Joy 2014 Human arm funded by Chemi Nutra grant; cell work funded by NIH; the same two consultants were authors but not involved in data collection or analysis
Andre 2016 Chemi Nutra grant to Baylor University; data collectors reported no financial interest
Escalante 2016 Funded by Max Muscle Sports Nutrition and Chemi Nutra; a co-author developed the product, and the principal investigator won $5,000 in the product’s body-transformation contest
Gonzalez 2017 Not stated in the abstract; we could not access the full text
Smeuninx 2019 Abbeyfield Research Foundation, Wellcome Trust and UK research councils; no conflicts declared; Chemi Nutra donated the product
Mobley 2015 (rats) Lab start-up funds and NIH; Chemi Nutra paid for cell-arm reagents and publication

Both significant training results came from company-funded trials, although company-funded Andre et al. reported no significant difference. Funding does not prove bias, but independent replication of the benefit is missing.

Side effects and risks

Human safety data

Safety data are thin. No serious problem has been reported, but the trials were not designed to find one:

  • Adverse events. Hoffman reported that PA and placebo were very well tolerated with no adverse events. Andre reported no adverse side effects. The Joy and Escalante papers do not report adverse-event data, and the Gonzalez abstract does not mention them.
  • Monitoring. The full-text training trials we read did not describe safety blood panels such as liver or kidney markers.
  • Duration and population. The muscle trials lasted at most 8 weeks and enrolled only men.
  • PA combined with phosphatidylserine. A trial in 40 women with premenstrual syndrome gave 400 mg PA plus 400 mg phosphatidylserine a day, or placebo, for 3 menstrual cycles and described this as safe. It tested a commercial Lipogen complex at a lower PA dose, so it cannot establish the safety of 750 mg of PA alone (Schmidt et al., Clin Nutr ESPEN 2018).

We found no data specific to pregnancy, lactation, adolescents or long-term use, and no formal toxicology study of a PA concentrate.

Animal and cell signals

These findings are not human evidence, but they are reasons not to treat “natural” as “proven safe”:

  • Intestinal tumors in rodents. Oral LPA has been reported to protect against gastric ulcers in rats and mice but worsen intestinal tumor development in mice. In tumor-prone rats given a carcinogen and a high-fat diet, an LPA-rich soybean phospholipid mixture dose-dependently increased colorectal tumor formation (Tsutsumi et al., Dig Dis Sci 2017). That mixture was rich in LPA, not PA, although Joy et al. and Winter et al. describe PA being converted to LPA.
  • Cancer cell signaling. One review reports elevated phospholipase D activity in virtually all cancers where it has been examined and describes PA-to-mTOR signaling as a survival signal for cancer cells (Foster, Biochim Biophys Acta 2009). We found no human data linking supplemental PA to cancer.

Interactions

PA competes with rapamycin for binding to mTOR in cell and muscle experiments, and Foster reports that high phospholipase D activity confers rapamycin resistance in cells. We found no human study of oral PA with sirolimus or other mTOR inhibitors, so whether supplemental PA changes their effect is unknown.

Soy

The tested ingredients are soy-derived, and soybeans are one of the nine major US food allergens (FDA Food Allergies). We found no allergy data specific to PA concentrates.

Key takeaways

  • The mTOR claim is mostly cell and rodent work. PA made inside muscle appears to help turn loading into mTOR signaling in rodents, and PA added to cell cultures raises it. We found no human study showing that an oral dose does this.
  • The training trials conflict. Five small 8-week trials in trained men included only one significant PA-alone result, about 1.2 kg more lean mass than placebo, and one significant result for a multi-ingredient blend.
  • The human biopsy study was negative. In 16 older men, a single dose of about 750 mg was followed by lower anabolic signaling and no exercise-related rise in muscle protein synthesis.
  • No meta-analysis exists that we could find. A 2022 scoping review concluded the evidence does not support PA for performance or body composition, and other reviews rate it as mixed.
  • Industry funding is common. At least four of the five training trials were funded by Chemi Nutra or a supplement company, and independent replication of a benefit is missing.
  • Safety is largely unstudied. Short trials reported few problems but did little monitoring, and there are no long-term data, no muscle-trial data in women and no human data on use with mTOR-inhibiting drugs.

Sources

  1. Hoffman JR, Stout JR, Williams DR, et al. Efficacy of phosphatidic acid ingestion on lean body mass, muscle thickness and strength gains in resistance-trained men. J Int Soc Sports Nutr. 2012;9(1):47. PubMed.
  2. Joy JM, Gundermann DM, Lowery RP, et al. Phosphatidic acid enhances mTOR signaling and resistance exercise induced hypertrophy. Nutr Metab (Lond). 2014;11:29. PubMed.
  3. Andre TL, Gann JJ, McKinley-Barnard SK, 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. J Sports Sci Med. 2016;15(3):532–539. PubMed.
  4. Escalante G, Alencar M, Haddock B, Harvey P. The effects of phosphatidic acid supplementation on strength, body composition, muscular endurance, power, agility, and vertical jump in resistance trained men. J Int Soc Sports Nutr. 2016;13:24. PubMed.
  5. Gonzalez AM, Sell KM, Ghigiarelli JJ, et al. Effects of phosphatidic acid supplementation on muscle thickness and strength in resistance-trained men. Appl Physiol Nutr Metab. 2017;42(4):443–448. PubMed.
  6. Smeuninx B, Nishimura Y, McKendry J, et al. The effect of acute oral phosphatidic acid ingestion on myofibrillar protein synthesis and intracellular signaling in older males. Clin Nutr. 2019;38(3):1423–1432. PubMed.
  7. Teixeira FJ, Tavares N, Matias CN, Phillips SM. The effects of phosphatidic acid on performance and body composition - a scoping review. J Sports Sci. 2022;40(3):364–369. PubMed.
  8. Bond P. Phosphatidic acid: biosynthesis, pharmacokinetics, mechanisms of action and effect on strength and body composition in resistance-trained individuals. Nutr Metab (Lond). 2017;14:12. PubMed.
  9. Valenzuela PL, Morales JS, Emanuele E, et al. Supplements with purported effects on muscle mass and strength. Eur J Nutr. 2019;58(8):2983–3008. PubMed.
  10. Kerksick CM, Wilborn CD, Roberts MD, et al. ISSN exercise & sports nutrition review update: research & recommendations. J Int Soc Sports Nutr. 2018;15(1):38. PubMed.
  11. Sainani KL. The problem with “magnitude-based inference”. Med Sci Sports Exerc. 2018;50(10):2166–2176. PubMed.
  12. Fang Y, Vilella-Bach M, Bachmann R, et al. Phosphatidic acid-mediated mitogenic activation of mTOR signaling. Science. 2001;294(5548):1942–1945. PubMed.
  13. Hornberger TA, Chu WK, Mak YW, et al. The role of phospholipase D and phosphatidic acid in the mechanical activation of mTOR signaling in skeletal muscle. Proc Natl Acad Sci U S A. 2006;103(12):4741–4746. PubMed.
  14. You JS, Lincoln HC, Kim CR, et al. The role of diacylglycerol kinase ζ and phosphatidic acid in the mechanical activation of mammalian target of rapamycin (mTOR) signaling and skeletal muscle hypertrophy. J Biol Chem. 2014;289(3):1551–1563. PubMed.
  15. Winter JN, Fox TE, Kester M, et al. Phosphatidic acid mediates activation of mTORC1 through the ERK signaling pathway. Am J Physiol Cell Physiol. 2010;299(2):C335–C344. PubMed.
  16. Mobley CB, Hornberger TA, Fox CD, et al. Effects of oral phosphatidic acid feeding with or without whey protein on muscle protein synthesis and anabolic signaling in rodent skeletal muscle. J Int Soc Sports Nutr. 2015;12:32. PubMed.
  17. Tanaka T, Kassai A, Ohmoto M, et al. Quantification of phosphatidic acid in foodstuffs using a thin-layer-chromatography-imaging technique. J Agric Food Chem. 2012;60(16):4156–4161. PubMed.
  18. Tsutsumi T, Inoue M, Okamoto Y, et al. Daily intake of high-fat diet with lysophosphatidic acid-rich soybean phospholipids augments colon tumorigenesis in Kyoto Apc Delta rats. Dig Dis Sci. 2017;62(3):669–677. PubMed.
  19. Foster DA. Phosphatidic acid signaling to mTOR: signals for the survival of human cancer cells. Biochim Biophys Acta. 2009;1791(9):949–955. PubMed.
  20. Schmidt K, Weber N, Steiner M, et al. A lecithin phosphatidylserine and phosphatidic acid complex (PAS) reduces symptoms of the premenstrual syndrome (PMS): results of a randomized, placebo-controlled, double-blind clinical trial. Clin Nutr ESPEN. 2018;24:22–30. PubMed.
  21. University of São Paulo. Effects of phosphatidic acid supplementation on strength and hypertrophic responses to strength training. ClinicalTrials.gov identifier NCT04277364. ClinicalTrials.gov.
  22. Food and Drug Administration. FDA 101: dietary supplements. FDA.
  23. Food and Drug Administration. GRAS Notice Inventory (search term “phosphatidic,” November 8, 2026). FDA.
  24. Food and Drug Administration. Food allergies. FDA.
  25. World Anti-Doping Agency. The 2026 Prohibited List. WADA 2026 Prohibited List.