Nutrition
All scientific research indicates that phosphatidic acid increases muscle mass via activation of the muscle-building enzyme mTOR, while potentially reducing the breakdown of muscle protein.
Phosphatidic acid is a compound consisting of a glycerol backbone with two fatty acid chains linked to the first and second carbon atoms and a phosphate group linked to the third carbon atom of the glycerol backbone. Phosphatidic acid is a phospholipid typically found in the cell membrane, where it acts as a secondary messenger involved in many different cellular signaling cascades (1). Through this cellular signaling capacity, phosphatidic acid can elicit an anabolic response in muscle cells.
Indeed, muscle contractions are believed to activate certain enzymes that cause biosynthesis of phosphatidic acid in muscle cells, thereby increasing phosphatidic acid levels and activation of mTOR-stimulated protein synthesis, which promotes muscle growth. One of the studies by Cleland and colleagues (2) showed that electrically stimulated muscle contractions in rats led to a doubling of phosphatidic acid concentrations. Other studies by O'Neil and colleagues (3) showed that increases in phosphatidic acid concentrations occur in response to eccentric contractions and that these increases in phosphatidic acid levels enhanced mTOR signaling for more than 12 hours.
Oral ingestion of phosphatidic acid has been shown to increase phosphatidic acid plasma concentrations as early as 30 minutes after ingestion, and phosphatidic acid concentrations remained elevated for up to seven hours (4). In combination, the increase in phosphatidic acid levels in the body from oral supplementation combined with endogenous production from weight training should result in greater muscle hypertrophy compared to resistance training alone.
Phosphatidic acid increases muscle growth and strength
Due to the potential of phosphatidic acid supplementation for muscle growth, several groups have investigated its muscle-building capacity. A groundbreaking study by Hoffman and colleagues (5) examined the effect of soy-derived phosphatidic acid on muscle growth and strength in 16 subjects with significant weight training experience. The subjects were divided into two groups, one of which consumed 750 mg of phosphatidic acid per day, while the other received only a placebo. During the experiment, all subjects trained with weights four times a week, using 70 percent of their maximum weight for one repetition (1RM) for all exercises throughout the eight-week study period.
At the end of the study, strength and body composition were examined in all subjects. The results showed that subjects who had used phosphatidic acid had a 12.7 percent increase in squat strength and a 2.6 percent increase in muscle mass, while subjects who had taken a placebo only increased their squat strength by 9.3 percent and their muscle mass by 0.1 percent. The results of this study strongly suggest that taking phosphatidic acid in combination with resistance training increased muscle mass and strength.
Soy-derived phosphatidic acid drives muscle growth
While phosphatidic acid clearly plays a critical role in stimulating mTOR-driven muscle growth, different sources of phosphatidic acid, such as soy or eggs, have slightly different chemical compositions, with varying levels of unsaturated or saturated fatty acid chains at the first and second carbon positions of the glycerol backbone. These variations in the chemical composition of phosphatidic acid could influence the impact on muscle growth. Phosphatidic acids containing one saturated and one unsaturated fatty acid, such as soy-derived phosphatidic acid, are believed to be more likely to promote cellular signaling events such as mTOR-activated muscle growth than phosphatidic acids containing two saturated fatty acids, such as egg-derived phosphatidic acid, which appear to be less biochemically active as a signaling compound (6).
To search for more efficient muscle-building forms of phosphatidic acid, a study by Joy and colleagues (7) investigated the differential impact of different types of phospholipids, including soy- and egg-derived phosphatidic acid, on muscle growth and strength. The study involved two independent experiments, the first of which examined the ability of soy- and egg-derived phosphatidic acid to activate mTOR in isolated muscle cells in vitro, and the second of which measured muscle growth rates in humans who ingested 750 mg of soy-derived phosphatidic acid daily while completing an eight-week periodized weight training program.
In the first experiment conducted by Joy and colleagues, the scientists found that of all the phospholipids studied, soy-derived phosphatidic acid produced the greatest increase in mTOR activity relative to the other phospholipids, including egg-derived phosphatidic acid. The second experiment confirmed the results of the first experiment, as soy-derived phosphatidic acid also produced a significant increase in muscle mass of 5 pounds relative to the placebo group. This experiment also showed a statistically significant increase in leg press strength of 115 pounds in the group taking phosphatidic acid, while members of the placebo group only increased their strength by 50 pounds.
Taken together, this study effectively shows that soy-derived phosphatidic acid activates mTOR more strongly and increases muscle mass and maximum strength when combined with resistance training. These results support the hypothesis that an unsaturated fatty acid found in soy-derived phosphatidic acid promotes superior gains in mass and strength. Thus, soy-derived phosphatidic acid appears to be the superior source of phosphatidic acid compared to egg-derived phosphatidic acid when it comes to increasing the effects of resistance training on muscle mass and strength.
Phosphatidic acid prevents muscle breakdown
Phosphatidic acid's ability to stimulate muscle growth may also be related to its recently discovered capacity to inhibit muscle breakdown, which ultimately leads to hypertrophy, as reduced muscle protein breakdown tends to increase muscle protein levels, thereby promoting muscle growth.
The first indication that phosphatidic acid could inhibit muscle protein breakdown came from a study that showed that increasing the amount of one of the enzymes that synthesizes phosphatidic acid in the body - PDL1 - in isolated muscle cells increased phosphatidic acid levels. This increase in phosphatidic acid levels rapidly reduced the expression of a number of genes that promote muscle protein degradation. (8) This study further showed that the same muscle-degrading genes were also silenced when the muscle cells were directly exposed to phosphatidic acid.
Interestingly, some of the genes involved in the protein-degrading pathway that are turned off by phosphatidic acid can be activated by the extremely potent muscle-degrading molecule myostatin, suggesting that phosphatidic acid may prevent some of the negative effects of myostatin on muscle growth.
Although these results are very intriguing, further research is certainly needed as the anti-catabolic effects of phosphatidic acid have so far only been demonstrated in vitro on muscle cells. Thus, further studies investigating the effects of phosphatidic acid in humans need to be carried out to fully confirm these results.
In summary, all of this scientific evidence suggests that phosphatidic acid increases muscle mass via activation of the muscle-building enzyme mTOR, while potentially reducing muscle protein breakdown. Such a likely dual effect as that of phosphatidic acid on muscle protein levels is typically very beneficial for muscle growth, as it not only provides an effective way to stimulate protein synthesis, but also a way to mitigate the often underestimated catabolic effect that intense weight training has on muscle tissue.
The positive influence of phosphatidic acid is even more pronounced when this supplement is optimally used in coordination with weight training sessions. The optimal supplement protocol for phosphatidic acid should include at least 750 mg of soy-derived phosphatidic acid taken immediately after exercise, as phosphatidic acid is available to the body within 30 minutes of oral ingestion and remains available for at least seven hours. This seven-hour post-workout window is, of course, the period during which the catabolic effects of training with weights are near their maximum and should be inhibited as quickly and strongly as possible to prevent potential muscle breakdown, which will ultimately lead to superior gains in muscle mass and strength.
References:
- Wang X, Devaiah SP, et al. Signaling functions of phosphatidic acid. Prog Lipid Res 2006; 45, 250-278.
- Cleland PJ, Appleby GJ, et al. Exercise induced translocation of protein kinase C and production of diacylglycerol and phosphatidic acid in rat skeletal muscle in vivo. Relationship to changes in glucose transport. J Biol Chem 1989: 246, 17704-17711.
- O'Neil TK, duffy LR, et al. The role of phosphoinositide 3-kinase and phosphatidic acid in the regulation of mammalian target of rapamycin following eccentric contractions. J Physiol 2009; 587, 3691-3701
- Purpura M, Jager R, et al. Effect of oral administration of soy-derived phosphatidic acid on concentrations of phosphatidic acid and lyso-phosphatidic acid molecular species in human plasma. J Int Sports nutr 2013; 10, 22
- Hoffman JR, Stout JR, 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, 47
- Foster DA. Regulation of mTOR by phosphatidic acid? Cancer Res 2007; 67, 1-4
- Joy JM, Gundermann DM, et al. Phosphatidic acid enhances mTOR signaling and resistance exercise induced hypertrophy. Nutr Metab (Lond) 2014; 11, 29
- Jaafar R, De Larichaudy J, et al. Phospholipase D regulates the size of skeletal muscle cells through the activation of mTOR signaling. Cell Commun Signal 2013; 11, 55
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Omega-3 fatty acids, found in fish oil, are among the most popular supplements on the planet. People use them to prevent premature death, improve cardiovascular health and prevent cancer, but little scientific research supports these effects.
Omega-3 fatty acid supplements protect people with a history of cardiovascular disease from heart attacks and sudden cardiac death. They may also promote mental health by preventing depression and inflammation in the brain. Furthermore, omega-3 fatty acids could prevent muscle loss in old age.
Scottish scientists administered six grams of fish oil per day or a placebo (fake fish oil) to older adults over a period of nine months. Omega-3 fatty acids promoted muscle protein synthesis and helped older people to maintain their muscle mass, but they had no effect on blood sugar regulation.
(British Journal of Nutrition, published online on November 5, 2015)
The human body contains small amounts of a calorie-burning tissue called brown adipose tissue, which converts food energy into heat. White fat does the opposite - it stores energy. Brown adipose tissue is an important heat-generating tissue in hibernating animals. It promotes non-shivering thermogenesis, which generates heat and helps animals and humans adapt to the cold. Brown adipose tissue accounts for up to 10 percent of total fat mass in people living in countries with a cold climate, such as northern Finland. Individual differences in the amount of brown fat and activity play an important role in human obesity.
Brown adipose tissue is activated by the sympathetic nervous system, which is the body's "fight or flight" system responsible for dealing with stress and emergencies. Increased activation of brown adipose tissue helps people consume more calories and burn more fat. Key nutrients such as L-arginine, L-citrulline and L-glutamine can increase brown adipose tissue activity, which increases calorie consumption and promotes fat burning. Classes of drugs believed to alter brown adipose tissue metabolism include the thiazolidinedione (TZD) class of peroxisome proliferator-activated receptor gamma agonists, and fibroblast growth factor 21 (FGF21) analogs. However, these drugs are still under investigation.
(Frontiers in Endocrinology, 6: Article 174, 2015)
The classic body is characterized by large muscle bellies accentuated by lean joints and, most importantly, a narrow waistline that is virtually free of belly fat. The routine approach to achieving this classic look involves hardcore training with weights to build muscle, combined with a reduced calorie intake to burn body fat. Low calorie diets can be grueling, especially if the calories consumed do not alleviate hunger and do not adequately replenish the body with nutrients after an intense workout with weights. Reducing food intake also tends to reduce metabolic rate, primarily due to a reduction in muscle mass, which makes it seemingly impossible to build muscle while reducing body fat. However, consuming the right nutrients such as whey protein, which has an amazing capacity to simultaneously reduce hunger, burn fat and stimulate muscle growth even while dieting, should speed up the process of creating the look of a classic body.
Eliminate fat with whey protein
Consuming larger amounts of protein typically promotes a loss of body fat. It is a fact that diets with a daily protein intake of 1.5 grams of protein per kilogram of body weight increase weight loss (1, 2) and body fat loss (2, 3). The consumption of certain types of protein such as whey protein, which are packed with the branched-chain amino acid leucine, has in fact been shown to be even more effective in stimulating fat loss than the consumption of proteins with a lower leucine content. A study conducted by Baer and colleagues that demonstrated this result showed that consuming 56 grams of whey protein per day for 23 weeks generated 5 pounds more fat mass loss compared to another group in the study that consumed an equivalent amount of calories in the form of carbohydrates instead of whey protein. The group consuming the whey protein also lost a full 2.5 inches more in waist circumference than the carbohydrate group, suggesting that much of the fat lost was belly fat.
Burn even more fat with whey protein
A key fat-burning mechanism stimulated by the use of whey protein is food-induced thermogenesis. This process involves the energy cost associated with metabolizing specific nutrients. A commonly used estimate for the thermogenic effect of food is roughly 10 percent of caloric intake, although this percentage can vary substantially depending on the type of macronutrient, with protein intake burning the most calories at about 23 percent, while this value is only 6 percent for carbohydrates and 3 percent for fats (5, 6). The superior thermogenic response to protein consumption relative to carbohydrate and fat consumption makes protein intake the best choice for stimulating thermogenic fat loss.
In addition to consuming more protein to stimulate thermogenic energy expenditure, changing the source of protein may also be an effective way to stimulate additional fat loss, as certain types of protein are more potent stimulators of thermogenesis. In fact, recent studies comparing the thermogenic effects of isocaloric protein-rich meals containing either whey protein, casein or soy protein report that whey protein elicited a much stronger thermogenic response. Whey protein also increased fat oxidation to a greater extent than casein or soy protein (7), making whey protein the clear protein of choice when it comes to reducing body fat.
Lose more fat and keep that fat off by suppressing your appetite with whey protein
Dietary proteins can have a significant impact on body fat levels by suppressing appetite. The appetite suppressing influence of protein consumption can vary based on the unique influence that different types of protein have on certain hormones after consumption. For example, it was recently shown that the production of glucagon-like peptide 1 (GLP-1) - a digestive tract hormone that reduces hunger - increased significantly in response to whey protein consumption, while other proteins such as soy protein had no effect on GLP-1 levels (8). The increased production of GLP-1 is supported by the fact that consumption of whey protein has been shown to reduce hunger more effectively than consumption of soy protein.
The increased GPL-1 concentration from consuming whey protein is likely caused to some extent by the fact that whey protein inhibits the enzyme dipeptidyl peptinase-4, which normally breaks down GLP-1. Thus, the ability of whey protein to inhibit this enzyme ultimately increases GLP-1 levels, thereby prolonging the hunger-reducing effects of this hormone (9). In addition, whey protein is supercharged with the amino acid leucine, which has the ability to completely deactivate the energy "measuring" hormone AMPK in the brain. This deactivation of AMPK in the brain directly reduces hunger, which further reduces food intake, resulting in greater fat loss (10).
Maintaining muscle mass while dieting with whey protein
Dieting to lose body fat and not muscle mass seems almost impossible, primarily due to the body's tendency to convert muscle tissue into energy to compensate for the calorie deficit caused by reduced food intake. The consumption of high-quality whey protein can prevent this protein breakdown, especially during a diet. This effect is due to the ability of protein intake to activate the enzyme mTOR, which directly increases levels of muscle protein synthesis while counteracting muscle protein breakdown.
Indeed, a study conducted by Hector and colleagues clearly showed that twice-daily supplementation with 27 grams of whey protein during low-calorie diets increased muscle protein synthesis rates more effectively than 27 grams of soy protein or 25 grams of the carbohydrate maltodextrin. This result shows that a whey protein intake is more effective in maintaining muscle protein and therefore muscle mass during low calorie diets. The authors of the study suggested that the superior effect of whey protein on muscle protein levels observed during this study was most likely caused by the higher leucine content of whey protein, as leucine is the primary driver of mTOR activation, which increases muscle protein synthesis and prevents muscle breakdown, thereby maintaining lean body mass even during dieting.
Whey protein and carnitine do not go together
Carnitine works by transporting fatty acids into the mitochondria, where they are burned to provide energy for the body. Despite the central role that carnitine plays in fatty acid oxidation, carnitine supplementation has been shown to have no effect on fat burning or fat loss when consumed on its own (12). However, a recent study by Wall and colleagues (13) demonstrated a way to increase muscle carnitine levels that actually increase fatty acid oxidation and fat loss. In this study, the researchers gave subjects carnitine while simultaneously administering insulin and glucose. This treatment generated a significant increase in carnitine levels, which stimulated fatty acid oxidation during high-intensity, submaximal exercise. These results suggest that cellular uptake of carnitine is increased when ingested with a glucose-rich meal, which stimulates insulin secretion and transports carnitine into muscle cells.
Since increasing muscle carnitine content represents a tempting intervention for type 2 diabetes and obesity, another study by Shannon and colleagues investigated whether whey protein in combination with a carbohydrate intake could reduce the overall need for carbohydrate to stimulate insulin-mediated carnitine uptake into muscle tissue, since whey protein is rich in leucine, which effectively stimulates insulin secretion. In addition, the ability of whey protein to promote fat loss and increase lean body mass makes whey protein a better choice than carbohydrates for this task, especially for people with type 2 diabetes and obese individuals. Despite these assumptions, the results of this study surprisingly showed that consuming whey protein with a lower amount of carbohydrate completely prevented carnitine uptake rather than increasing it - and this despite an increase in insulin levels that was comparable to the increase in insulin levels in the carbohydrate-only group. The conclusion of this study is that the combined use of protein and carbohydrate to increase carnitine levels for the purpose of fat loss is probably inefficient and therefore cannot be recommended.
References
- Piatti PM, Monti F, et al. Hypocaloric high-protein diet improves glucose oxidation and spares lean body mass: comparison to hypocaloric high-carbohydrate diet. Metabolism 1995; 43, 1481 - 1487
- Skov AR, Toubro S, et al. Randomized trial in protein vs carbohydrate in ad libitum fat reduced diet for treatment of obesity. Int J Obes Relat Metab Disord 1999; 23, 528 - 536
- Parker B, Noakes M, et al. Effect of a high-protein, high-mononunsaturated fat weight loss diet on glycemic control and lipid levels in type 2 diabetes. Diabetes Care 2002; 25, 425 - 430
- Baer DJ, Stote KS, et al. Whey protein but not soy protein supplementation alters body weight and composition in free-living overweight and obese adults. J Nutr 2011; 141, 1489 - 1494
- Tappy L, Jequier E and Acheson K. Thermic effect of infused amino acids in healthy humans and in subjects with insulin resistance. Am J Clin Nutr 1993; 57, 912 - 916
- Acheson KJ, Ravussin E, et al. Thermic effect of glucose in man. Obligatory and facultative thermogenesis. J Clin Invest 1984; 74, 1572 - 1580
- Acheson KJ, Blondel-Lubrano A, et al. Protein choices targeting thermogenesis and metabolism. Am J Clin Nutr 2011; 93, 525 - 534
- Veldhorst MA, Nieuwenhuizen AG, et al. Dose dependant satiating effect of whey relative to casein or soy. Physiol Behav 2009; 96, 675 - 682
- Gunnarsson PT, Winzell MS, et al. Glucose-induced incretin hormone release and inactivation are differently modulated by oral fat and protein in mice. Endocrinology 2006; 147, 3173 - 3180
- Saha AK, Xu XJ, et al. Downregulation of AMPK accompanies leucine- and glucose-induced increases in protein synthesis and insulin resistance in rat skeletal muscle. Diabetes 2010; 59, 2426 - 2434
- Hector AJ, Marcotte GR, et al. Whey protein supplementation preserves postprandial myofibrillar protein synthesis during short-term energy restriction in overweight and obese adults. J Nutr 2015; 145, 246 -252
- Villani RG, gannon J, et al. L-Carnitine supplementation combined with aerobic training does not promote weight loss in moderately obese women. Int J Sport Nutr Exerc Metab 2000; 10, 100 - 207
- Wall BT, Stephens FB, et al. Chronic oral ingestion of L-carnitine and carbohydrate increases muscle carnitine content and alters muscle fuel metabolism during exercise in humans. J Physiol 2011; 589, 963 - 973
- Shannon CE, Nixon AV, et al. Protein ingestion acutely inhibits insulin-stimulated muscle carnitine uptake in healthy young men. Am J Clin Nutr 2016; 103, 276 - 282
The U.S. Department of Agriculture recommends a daily protein intake of 0.8 grams per kilogram of body weight. Active people could benefit from up to 1.5 grams of protein per kilogram of body weight.
Jose Antonio and colleagues from Nova Southeastern University in Florida found that a high protein intake (3.4 grams per kilogram of body weight per day) combined with a periodized exercise program with weights over an 8-week period resulted in a greater reduction in body weight, body fat percentage and fat mass than 2.3 grams of protein per kilogram of body weight. There were no differences in fat-free mass.
Previous studies have shown that a very high protein intake without training with weights did not change body composition. The scientists concluded that intensively training athletes would benefit from a protein intake higher than two grams of protein per kilogram of body weight per day.
(Journal International Society Sports Nutrition, 13: 3, 2016)
