BCAA vs Leucine Supplements: Latest Studies
Branched-chain amino acids (BCAAs), or a leucine supplements, are best taken after exercise. Leucine, isoleucine and valine are called branched-chain amino acids (BCAAs) and they are essential amino acids, which means they must be consumed in the diet. BCAAs help to build muscle since they are involved in protein synthesis, tissue repair, signaling a biochemical pathway essential for muscle protein synthesis (i.e., mTOR) and blood sugar control. A meta-analysis that combined the results of seven studies showed that BCAA supplements are best taken after exercise, not before or during exercise (intra-workout). The studies revealed that BCAAs taken during exercise are “not effective on muscle soreness at follow-up time,” the researchers wrote.
Leucine consumption before your workout promotes sluggishness and fatigue. Recent research has shown that leucine competitively inhibits the dopamine precursor tyrosine into the brain and reduces dopamine levels. Dopamine and noradrenaline are the “flight-or-fight” hormones that allow the body to perform at higher levels than normal. Increasing dopamine reduces fatigue and increases mental arousal, focus, confidence and greater levels of motivation. Pre-workout leucine and BCAA consumption is not the best for optimal muscular performance.
According to the meta-analysis, when BCAAs are taken after exercise, they reduce post-exercise muscle soreness and creatine kinase— a marker of muscle damage— better than rest alone.
BCAAs promote recovery by stimulating the mTOR pathway to increase protein synthesis to repair injured tissue. Leucine, one of the BCAAs, is the most important chemical that turns on the mTOR pathway, so it is likely that consuming leucine after exercise would be more effective (and cheaper) than consuming BCAAs. The addition of isoleucine and valine may hinder the benefits of leucine due to competition for transport into muscle cells. The BCAAs share the same active transport system into cells and muscle cells. Indeed, isoleucine and valine have been shown to inhibit absorption of leucine. In the March 2018 issue of the International Journal of Sports Nutrition and Exercise Metabolism, it was reported that men fed 6 grams of whey protein supplemented with leucine, isoleucine and valine observed less protein synthesis than whey protein supplemented with just leucine. Also, research has shown that valine can cause insulin resistance in muscle, which is detrimental to muscle growth and enhances the accumulation of body fat. Recent research has also found that valine is associated with higher risk of hypertension.
Benefits of leucine:
- Leucine is the key anabolic trigger to protein synthesis.
- Increase in muscle protein synthesis are dependent on leucine concentration.
- 5 grams of leucine can increase the anabolic effects of protein synthesis when eating less protein, which is ideal on a ketogenic diet.
- Research has shown 6.25 grams of whey protein with 5 grams of leucine is equivalent to at least 25 grams of whey protein.
- Anabolic resistance in people over 40 can be overcome by consuming greater quantities of leucine.
- Leucine and not total protein content of a supplement is the primary determinant of muscle protein anabolic responses in healthy older people.
- Research has shown that pure leucine is more anabolic than protein in food!
- Leucine is the key amino acid for enhancing mTOR pathway that regulates cell growth and protein synthesis.
- Leucine has many benefits: powering muscle growth, preventing muscle loss especially during low-calorie, low-carb or ketogenic diets.
For best results as an anabolic trigger, take 5 grams of leucine (on an empty stomach) 15-30 minutes before a post-workout meal. By taking pure leucine on an empty stomach, you will get a better spike in blood levels than if you take leucine with food, because food can slow leucine’s absorption. When leucine is taken on an empty stomach, it’s a powerful metabolic switch that turns on protein synthesis. Leucine increases mTOR activity for several hours after training. When leucine is taken after resistance exercise and before a post-workout protein-containing meal rich in essential amino acids, it triggers greater protein synthesis for improved recovery and greater gains
Leucine. The Most Potent BCAA: the Anabolic Trigger
Leucine has many benefits: powering muscle growth, preventing muscle loss, increasing insulin sensitivity, enhancing fat metabolism and enhancing recovery.
Increases Muscle Protein Synthesis. Muscles increase in size when muscle protein synthesis is greater than muscle breakdown. Protein balance is influenced by muscle tension, physical activity, calories, protein and amino acids. High protein intake temporarily increases protein synthesis in the muscles by activating key biochemical pathways in the cells. When combined with protein, leucine triggers protein synthesis for greater gains.
A study from Maastricht University Medical Center in the Netherlands found that supplementing 20 grams of casein protein and 2.5 grams of crystalline leucine increased protein synthesis in older men 20 percent greater than protein alone. Researchers used sophisticated chemical tracers to measure protein synthesis.
Stuart Phillips from McMaster University in Canada, with colleagues, found that a supplement containing 25 grams of whey protein was optimal for stimulating muscle protein synthesis. Consuming less whey slowed protein synthesis. However, consuming low levels of protein (6.25 grams) but adding a leucine supplement caused the same rate of protein synthesis as the 25-gram supplement. Supplements containing 25 grams of whey protein are optimal for stimulating muscle protein synthesis. You can achieve the same result by consuming less whey protein but adding leucine supplements.
Muscle loss is a serious problem in older adults, leading to decreased quality of life, diabetes and premature death. Dietary protein is an important stimulator of muscle protein synthesis. Older adults can stimulate muscle protein by consuming supplements containing protein and leucine several times per day, containing 20 to 30 grams of protein. (Clinical Nutrition 2013, 32: 412-419; Journal of Physiology 2012, 590: 2751-2765)
Increases Insulin Sensitivity. Long-term leucine supplementation increased insulin sensitivity and lean bodyweight, according to a Chinese study on rats. They gave rats high doses of leucine for 24 weeks. The scientists speculated that leucine worked by reducing oxidative stress and improving insulin signaling. Leucine is the real deal when it comes to muscle-promoting supplements, particularly in older adults. (Molecular Nutrition & Food Research 2013, 57: 1067-1079)
Enhances Fat Metabolism. Leucine builds proteins and chemically signals key metabolic pathways. Higher dietary intake of leucine is linked to a reduced risk of obesity. Researchers from Suzhou University in China, in a study on mice fed a high-fat diet, found that long-term leucine supplementation enhanced fat metabolism, prevented fat and weight gain, reduced fat accumulation in the liver and increased brown fat activity.
Leucine activates the mTOR pathway, which is important for muscle protein synthesis. It stimulates brown fat, which helps regulate bodyweight by converting food energy to heat instead of storing it as fat. Leucine is an important supplement for building lean body mass. Whey protein is high in leucine, but athletes benefit from additional leucine supplements (about 3-5 grams). (Food & Nutrition Research, published online September 9, 2016)
Prevents Muscle Wasting. Muscle atrophy (muscle loss) is a serious problem in older adults and bedridden patients. Muscle is critical for quality of life. Muscle loss reduces the ability to move, and promotes painful joints. Muscle is the largest tissue in the body and is critical for metabolic health. Muscle loss reduces the capacity to control blood sugar and other fuels and makes it more difficult to control blood pressure, blood fats and fat deposition.
Leucine supplements are a simple, effective way to reduce muscle loss in bedridden patients and older adults. A series of studies from the University of Texas Medical Branch in Galveston found that feeding leucine mixed in a cocktail of essential amino acids and carbohydrates reduced muscle loss by half during 28 days of bed rest. Bedridden people usually have reduced appetites, which promote muscle loss. Feeding 3-5 grams of leucine is an easy way to promote muscle protein synthesis and prevent muscle breakdown. (Nutra Ingredients-usa.com, published online August 26, 2013)
Prevents Muscle Loss During Bed Rest. Too much bed rest will kill you! In 1947, British physician Richard Asher wrote, “Teach us to live that we may dread unnecessary time in bed. Get people up and we may save our patients from an early grave.” Bed rest studies by scientists from NASA showed that three weeks of total bed rest (not allowed to get out of bed during the experiment) caused a 25 percent decrease in aerobic capacity, a 13 percent decrease in muscle mass and a 25 to 35 percent decrease in strength and power.
Everyone gets sick occasionally, so how do you maintain precious training gains when you have to stay in bed? A study led by Kirk English from the University of Texas Medical Branch in Galveston, Texas found that supplementing the amino acid leucine with every meal (0.06 grams per kilogram of bodyweight) during 14 days of bed rest prevented some changes in muscle mass, strength, power and body fat, compared to a placebo (fake leucine). Leucine is an amino acid that acts as a chemical signal to turn on protein synthesis in the muscle cells. Leucine can prevent physical deterioration during short breaks in training or when you are confined to bed with the flu. (American Journal Clinical Nutrition 2016, 103: 465-473)
BCAA Leucine Is Best Taken After Exercise. Leucine, isoleucine and valine are called branched-chain amino acids (BCAAs). They are essential amino acids, which means they must be consumed in the diet. BCAAs are involved in protein synthesis, tissue repair, signaling a biochemical pathway essential for muscle protein synthesis (i.e., mTOR) and blood sugar control. A meta-analysis that combined the results of seven studies showed that BCAA supplements are best taken after exercise, not before or during exercise (intra-workout). The studies revealed that BCAAs taken during exercise are “not effective on muscle soreness at follow-up time,” the researchers wrote.
Consumption of a Leucine supplement before your workout promotes sluggishness and fatigue. Recent research has shown that leucine competitively inhibits dopamine precursor tyrosine into the brain, and reduces dopamine levels. Dopamine and noradrenaline are the “flight-or-fight” hormones that allow the body to perform at higher levels than normal. Increasing dopamine reduces fatigue and increases mental arousal, focus, confidence and greater levels of motivation. Pre-workout leucine and BCAA consumption is not the best for optimal muscular performance.
According to the meta-analysis, when BCAAs are taken after exercise, they reduce post-exercise muscle soreness and creatine kinase— a marker of muscle damage— better than rest alone.
BCAAs promote recovery by stimulating the mTOR pathway to increase protein synthesis to repair injured tissue. Leucine, one of the BCAAs, is the most important chemical that turns on the mTOR pathway, so it is likely that consuming leucine after exercise would be more effective (and cheaper) than consuming BCAAs. The addition of isoleucine and valine may hinder the benefits of leucine due to competition for transport into muscle cells. The BCAAs share the same active transport system into cells and muscle cells. Indeed, isoleucine and valine have been shown to inhibit absorption leucine. In the March 2018 issue of the International Journal of Sports Nutrition and Exercise Metabolism, it was reported that men fed 6 grams of whey protein supplemented with leucine, isoleucine and valine observed less protein synthesis than whey protein supplemented with just leucine. Also, research has shown that valine can cause insulin resistance in muscle, which is detrimental to muscle growth and enhances the accumulation of body fat.
For best results as an anabolic trigger, take 5 grams of leucine (on an empty stomach) 15-30 minutes before a post-workout meal. By taking pure leucine on an empty stomach, you will get a better spike in blood levels than if you take leucine with food, because food can slow leucine’s absorption. When leucine is taken on an empty stomach, it’s a powerful metabolic switch that turns on protein synthesis. Leucine increases mTOR activity for several hours after training. When leucine is taken after resistance exercise and before a post-workout protein-containing meal rich in essential amino acids, it triggers greater protein synthesis for improved recovery and greater gains. (Nutrition 2017, 42: 30-36; American Journal of Clinical Nutrition 2016; 104:1594-606; Med Sci Sports Exercise 2011, 43: 2249-2258; Nat Med 2015, 22: 421-426; Biochemical Journal 1996, 100: 7-11; International Journal of Sport Nutrition and Exercise Metabolism, March 2018, 28: 170-177)
High BCAAs Bad For Your Health, But Not Leucine
A study on branched-chain amino acids (BCAAs) published May 8th, 2022, in the journal Aging Cell reported that “specific composition of dietary protein may be a previously unappreciated driver of metabolic dysfunction and that BCAA restricted diets may be a promising new approach to delay or prevent diseases of aging.”
The report says that “over 50 years ago, it was discovered the plasma levels of BCAAs are positively correlated with insulin resistance and obesity in humans. This has been expanded upon in recent studies of obese and insulin resistant humans around the world.” Insulin resistance occurs when the body becomes resistant to the hormone insulin. According to the Mayo Clinic, “Glucose can’t enter the cells as easily, so it builds up in the blood. This can eventually lead to type 2 diabetes.” High BCAA levels in the blood are present in diabetics. Also “more recently, elevated BCAAs have been associated with negative cardiovascular outcomes.”
This report says that the catabolite of valine, 3-hydroxyisobutyrate (3-HIB), can enhance fat accumulation in skeletal muscle. 3-HIB can create fatty muscles – a contributor to insulin resistance. Also “elevated BCAAs are specifically associated to poor health outcomes in humans overall, and higher blood levels of isoleucine are associated with increased mortality” and “higher dietary levels of isoleucine are associated with body mass index” and obesity.”
The report says that “there are many factors that need to be considered in the application of experimental diets to human patients, mainly safety and feasibility. BCAA restricted diets could conceptually be used as a weight loss and insulin-sensitizing intervention or promote healthy longevity,” and that “feeding and isoleucine restricted diet and testing the effects on longevity is the logical next step.”
A study published February 19th, 2022 in the journal Diabetes, Metabolic Syndrome and Obesity reported that the BCAA valine is strongly linked and correlated to insulin resistance and diabetes. The study involved a Chinese population of 816 individuals. The conclusion of the study found that “L-valine is an independent risk factor of oxidative stress and that high valine levels with oxidative stress could be a significant risk factor for increased type 2 diabetes.”
It has been implicated that the branched-chain amino acids isoleucine and valine, but not leucine, are positively associated with increase of insulin resistance, diabetes and obesity in animals as well as humans. Over 70% of Americans are overweight. Medical researchers have projected that by 2030, one in two adults will be obese. A major health concern!
It was reported May 13th, 2022 by Medical Xpress that “A new study from Pennington Biomedical Research Center, published in the journal Nature Communications found that reducing the amount of protein in the diet produced an array of favorable health outcomes including an extension of lifespan, and that these effects depend on a liver-derived metabolic hormone called fibroblast growth factor 21 (FGF-21).”
This study goes on to say that “it has long been known that the reducing the amount you eat improves health and extends lifespan, and that there has been increasing interest in the possibility that reducing protein or amino acid intake contributes to this beneficial effect.” Can restricting isoleucine in the diet raise FGF-21, and life-enhancing effects?
“This groundbreaking research has implications for extending the health and lifespan of people. If scientists can better understand how diets and nutritional hormones like FGF-21 act to extend lifespan, these discoveries could offset many of the health issues that occur in the middle age and later,” said Pennington Biomedical Executive Director John Kerwin, Ph.D.
The study published May 8th, 2022, in the journal Aging Cell says that isoleucine restriction in the diet strongly raised FGF-21! “The molecular mechanism by which FGF-21 levels are increased by isoleucine restriction, and the molecular processes by which dietary isoleucine restriction promotes glucose tolerance and reduces adiposity, remains to be determined.”
This new breakthrough research is essential for the metabolic benefits and lifespan extension of protein or isoleucine restriction. In conclusion, research has shown that limiting BCAAs valine and isoleucine, but not leucine, in the diet may delay aging and promote healthy longevity.
A study published June 2022 in the journal Atherosclerosis, researchers “conducted a systematic review with meta-analysis of non-perspective and prospective clinical studies to assess the effects of circulating branched-chain amino acids (BCAAs), including isoleucine, valine and leucine, on cardiovascular disease (CVD) risk.” The meta-analysis included “11 non-prospective studies involving 2,806 participants and 10 prospective studies involving 43,895 participants reported correlation between BCAAs and CVD risk.”
“This is the first systematic review and meta-analysis to investigate associations between circulating BCAA levels and the risk of CVD across a large sample. Current evidence suggests that circulating isoleucine levels are significant and positively correlated with CVD development. Compared to patients with low isoleucine levels, those with high levels have an increased risk for CVD. However, circulating valine and leucine levels do not appear to be significant factors in developing CVD.”
Over the last couple of years, I have been a big proponent of the essential amino acid leucine for activating the anabolic trigger of protein synthesis in muscle over branched-chain amino acid mixtures containing leucine, isoleucine and valine (BCAAs). Branched-chain amino acid mixtures (BCAAs) refer to three amino acids: leucine, valine and isoleucine. Over the years, the popularity of BCAA mixtures has grown with the false understanding that BCAAs alone are most effective for increasing the anabolic drive in muscle protein synthesis. The research has shown that taking pure leucine is more effective than the combination of BCAAs (leucine, isoleucine and valine). Research has also shown that leucine alone (not isoleucine and valine) is anabolic, and enhances protein synthesis (Journal of Physiology, 2013). Research has demonstrated that isoleucine and valine limit the effectiveness of leucine when taken together! Isoleucine and valine compete for absorption into the blood and into muscle cells. All three BCAAs share the active transport system. Research in humans has shown that taking BCAAs (leucine, isoleucine, valine) together can decrease muscle protein synthesis. That’s why I recommend leucine by itself over BCAA mixtures because combining BCAAs might limit the stimulation of protein synthesis because of reduced uptake of leucine in the blood and in muscle cells.
Leucine is Still King
Over the last couple of years, I have been a big proponent of the essential amino acid leucine for activating the anabolic trigger of protein synthesis in muscle over branched-chain amino acid mixtures containing leucine, isoleucine and valine (BCAAs). Branched-chain amino acid mixtures (BCAAs) refer to three amino acids: leucine, valine and isoleucine. Over the years, the popularity of BCAA mixtures has grown with the false understanding that BCAAs alone are most effective for increasing the anabolic drive in muscle protein synthesis. The research has shown that taking pure leucine is more effective than the combination of BCAAs (leucine, isoleucine and valine). Research has also shown that leucine alone (not isoleucine and valine) is anabolic, and enhances protein synthesis (Journal of Physiology, 2013). Research has demonstrated that isoleucine and valine limit the effectiveness of leucine when taken together! Isoleucine and valine compete for absorption into the blood and into muscle cells. All three BCAAs share the active transport system. Research in humans has shown that taking BCAAs (leucine, isoleucine, valine) together can decrease muscle protein synthesis. That’s why I recommend leucine by itself over BCAA mixtures because combining BCAAs might limit the stimulation of protein synthesis because of reduced uptake of leucine in the blood and in muscle cells. Leucine (5 grams) should be taken preferably post-workout 30-60 minutes before a post-workout meal to activate the anabolic trigger of protein synthesis. Research has shown that pure leucine is more anabolic than the same amount of leucine in food. A Japanese study published on October 18, 2018 in the journal Nutrients found that taking leucine supplements alone may be better for muscle protein synthesis and more anabolic than leucine from food! Japanese researchers found that blood levels of leucine were higher from pure, free leucine taken alone compared to the same amount of leucine in a meal. Increase in muscle protein synthesis is dependent on leucine concentration. Research has shown that leucine stimulates the anabolic effect of muscle protein on its own (Wilkinson et al., J Physiol 2013). The Nutrients study stated that, “based on these findings, it is presumed that compared to the intake of protein alone or free amino acids alone, the intake of dietary protein from mixed meals may result in a lower maximum plasma leucine concentration.” However, no study to date has investigated the changes in amino acid concentrations after the ingestion of mixed meals in comparison to those after the intake of a similar amount of free amino acids (Nutrients, October 2018). The post- workout meal will provide all the essential amino acids for optimal muscle protein synthesis.
A most review on branched-chain amino acid intake and muscle protein synthesis in humans was published September 2019 in the journal Einstein. This is a terrific updated review! The review acknowledges that, “leucine alone is able to induce a muscle protein synthesis response via activation of the mechanistic target of rapamycin complex 1 (mTOR1), a vital cell growth regulator.” The review goes on to say that, 6.25 grams of whey protein enriched with 5 grams of pure leucine was able to sustain protein synthesis up to 4.5 hours, which is the same amount found in NEW AML™ THERMO HEAT® FAT BURNING PROTEIN! Adding 3 grams each of isoleucine and valine to the 5 grams of leucine and 6.25 grams of whey protein hindered protein synthesis. Therefore, the addition of the other two BCAAs (valine and isoleucine) may have limited sustained muscle protein synthesis! To quote that study, “Potential reasons why the suboptimal whey protein dose containing 5g of leucine and high amounts of valine and isoleucine failed to sustain muscle protein synthesis were also investigated. It was argued that BCAA may compete for the same carrier in intestinal and muscle cells. Therefore, addition of the other two BCAA may have limited sustained muscle protein synthesis due to lower leucine uptake by cells, as suggested by lower blood and intracellular leucine levels in the first hour post-intake in participants receiving this treatment. Leucine apparently stimulates muscle protein synthesis after resistance physical exercise; however, as with other BCAA, the full range of EAA must be available in levels that will not promote competition for cell carriers or limit their action.”
Can Leucine Protect Against Cardiovascular Disease
A study in the Journal Biofactors (February 15, 2018) showed that leucine might be protective of cardiovascular disease in humans by “…attenuating macrophage foam-cell formation by mechanisms related to the metabolism of cholesterol, triglycerides and energy production.” “Foam cells are a type of macrophage that localize to fatty deposits on blood vessel walls, where they ingest low-density lipoproteins and become laden with lipids, giving them a foamy appearance. These cells secrete various substances involved in plaque growth and their death promotes inflammation, thereby contributing to cardiovascular disease.” (Nature, https://www.nature.com/subjects/foam-cells.)
Best Leucine Supplement
AML™ THERMO HEAT® FAT BURNING PROTEIN also contains vitamin D3, which enhances the anabolic effects of leucine. Research has shown that leucine combined with vitamin D3 can preserve muscle mass. Vitamin D3 is the most active form of vitamin D and can potentiate protein synthesis and the muscle-enhancing effects of leucine!
AML™ THERMO HEAT® FAT BURNING PROTEIN is an advanced, scientifically designed protein and amino acid drink based on the latest cutting-edge scientific research! As part of a low-carbohydrate, ketogenic diet and exercise program (aerobic and resistance training), it can help enhance protein synthesis and muscle growth and preserve lean body mass when following a low-carbohydrate ketogenic diet. Remember, a healthy weight loss is one that enhances reduction of body fat, enhances muscle growth and preserves lean body mass. Losing muscle mass during dieting can decrease one’s metabolic rate and result in burning fewer calories over a 24-hour period.
In conclusion, AML™ THERMO HEAT® FAT BURNING PROTEIN is a better whey to lose weight and preserve lean body mass during dieting. AML™ THERMO HEAT® FAT BURNING PROTEIN is more biologically active than ordinary whey protein because of the higher amounts of leucine and vitamin D3! Remember, a healthy weight loss is one that enhances reduction of body fat and preserves lean body mass during dieting.
REFERENCES:
- Wolfe R. Branched-chain amino acids and muscle protein synthesis in humans: myth or reality? Journal of the International Society of Sports Nutritionvolume 14, Article number: 30 (August 22, 2017)
-
Devries M, McGlory C, Bolster D et al. Leucine, Not Total Protein, Content of a Supplement Is the Primary Determinant of Muscle Protein Anabolic Responses in Healthy Older Women, The Journal of Nutrition, Volume 148, Issue 7, July 2018, Pages 1088-1095, https://doi.org/10.1093/jn/nxy091
- Liberman K, Njemini R, Luiking Y et al. Thirteen weeks of supplementation of vitamin D and leucine-enriched whey protein nutritional supplement attenuates chronic low-grade inflammation in sarcopenic older adults: the PROVIDE study. Aging Clin Exp Res, June 2019;31(6):845-854. doi:10.1007/s40520-019-01208-4
- Szwiega S, Rafii M, Pencharz P et al. The Leucine Requirement for Elderly Men Is More Than Double the Current Recommendations (P01-015-19). Curr Dev Nutr 2019;3(Suppl 1):nzz028.P01-015-19. Published 2019 Jun 13. doi:10.1093/cdn/nzz028.P01-015-19
- Arentson-Lantz E, Galvan F, Deer R, Wacher A, Paddon-Jones D. Leucine Supplementation Partially Protects Leg Lean Mass in Older Adults During Seven Days of Bed Rest (OR18-02-19). Curr Dev Nutr 2019;3(Suppl 1):nzz028.OR18-02-19. Published 2019 Jun 13. doi:10.1093/cdn/nzz028.OR18-02-1
-
Zheng R, Huang S, Zhu J et al. Leucine attenuates muscle atrophy and autophagosome formation by activating PI3K/AKT/mTOR signaling pathway in rotator cuff tears. Cell Tissue Res 2019. https://doi.org/10.1007/s00441-019-03021-x
-
Churchward-Venne T, Breen L, Di Donato D et al. Leucine supplementation of a low-protein mixed macronutrient beverage enhances myofibrillar protein synthesis in young men: a double-blind, randomized trial. The American Journal of Clinical Nutrition, Volume 99, Issue 2, February 2014, Pages 276-286, https://doi.org/10.3945/ajcn.113.068775
-
Yoshimura Y, Bise T, Takatsuk F et al. Effects of a leucine-enriched amino acid supplement on muscle mass, muscle strength, and physical function in post-stroke patients with sarcopenia: A randomized controlled trial. February 2019 Nutrition https://www.sciencedirect.com/science/article/pii/S089990071830594X?via%3Dihub
- Yoshii N at al Nutrients 2018, 10(10), 1543; https://doi.org/10.3390/nu10101543 Effect of Mixed Meal and Leucine Intake on Plasma Amino Acid Concentrations in Young Men.
- Rahimi MH, Shab-Bidar S et al. Branched-chain amino acid supplementation and exercise-induced muscle damage in exercise recovery: A meta-analysis of randomized clinical trials. Nutrition 2017.
- Chad M Kerksick, C Colin, D Wilborn, Michael D.ISSN exercise & sports nutrition review update: research & recommendations.
- Roberts et al. Journal of the International Society of Sports Nutrition 2018 15:38 https://doi.org/10.1186/s12970-018-0242-y 1 June 2018
- Szmelcman S, Guggenheim K. Interference between leucine, isoleucine and valine during intestinal absorption. Biochemical Journal 1966;100(1):7-11.
- Wilkinson DJ et al. Effects of leucine and its metabolite beta-hydroxy-beta-methylbutyrateonhumanskeletalmuscleproteinmetabolism. J.Physiol.2013,591,2911-2923.
- Dietary Intakes of Branched Chain Amino Acids and the Incidence of Hypertension: A Population-Based Prospective Cohort Study.Parvin Mirmiran, PHD, Farshad Teymoori, PHD, Golaleh Asghari, PHD, Fereidoun Azizi, MD. Arch Iran Med. April 2019;22(4):182-188.
- Tessier AJ, Chevalier S. An Update on Protein, Leucine, Omega-3 Fatty Acids, and Vitamin D in the Prevention and Treatment of Sarcopenia and Functional Decline. Nutrients. 2018;10(8):1099. Published 2018 Aug 16. doi:10.3390/nu10081099.
- Mardinoglu, Adil et al. Elevated Plasma Levels of 3-Hydroxyisobutyric Acid Are Associated With Incident Type 2 Diabetes EBioMedicine, Volume 27, 151-155, Jan. 2018.
-
Andersson-Hall U, Gustavsson C, Pedersen A et al. Higher Concentrations of BCAAs and 3-HIB Are Associated with Insulin Resistance in the Transition from Gestational Diabetes to Type 2 Diabetes. Journal of Diabetes Research, vol. 2018, Article ID 4207067, 12 pages, 2018. https://doi.org/10.1155/2018/4207067.
-
Binder E, Bermúdez-Silva FJ, André C, Elie M, Romero-Zerbo SY, et al. Leucine Supplementation Protects from Insulin Resistance by Regulating Adiposity Levels. (2013) Leucine Supplementation Protects from Insulin Resistance by Regulating Adiposity Levels. PLOS ONE 8(9): e74705. https://doi.org/10.1371/journal.pone.0074705
-
Lydia-Ann LS, Harris, Gordon I Smith, Bruce W Patterson, Raja S Ramaswamy et al. Alterations in 3-Hydroxyisobutyrate and FGF21 Metabolism Are Associated With Protein Ingestion-Induced Insulin Resistance. Diabetes 2017;66:1871-1878 https://doi.org/10.2337/db16-1475
- Trautman ME, Richardson NE, Lamming DW. Protein restriction and branched-chain amino acid restriction promote geroprotective shifts in metabolism. Aging Cell. 2022 May 8:e13626. doi: 10.1111/acel.13626. Epub ahead of print. PMID: 35526271.
-
Mice live longer and lose weight while eating more when FGF21 is Present. May 13, 2022. Pennington Biomedical Research Center. https://medicalxpress.com/news/2022-05-mice-longer-weight-fgf21.html
-
Hill, C.M., Albarado, D.C., Coco, L.G. et al. FGF21 is required for protein restriction to extend lifespan and improve metabolic health in male mice. Nat Commun 13, 1897 (2022). https://doi.org/10.1038/s41467-022-29499-8
- Li S, Jia H, Liu Z, Wang N, Guo X, Cao M, Fang F, Yang J, Li J, He Q, Guo R, Zhang T, Kang K, Wang Z, Liu S, Cao Y, Jiang X, Ren G, Wang K, Yu B, Xiao W, Li D. Fibroblast growth factor-21 as a novel metabolic factor for regulating thrombotic homeostasis. Sci Rep. 2022 Jan 10;12(1):400. doi: 10.1038/s41598-021-00906-2. PMID: 35013379; PMCID: PMC8748457.
- Hill CM, Albarado DC, Coco LG, Spann RA, Khan MS, Qualls-Creekmore E, Burk DH, Burke SJ, Collier JJ, Yu S, McDougal DH, Berthoud HR, Münzberg H, Bartke A, Morrison CD. FGF21 is required for protein restriction to extend lifespan and improve metabolic health in male mice. Nat Commun. 2022 Apr 7;13(1):1897. doi: 10.1038/s41467-022-29499-8. PMID: 35393401; PMCID: PMC8991228.
- Green CL, Lamming DW, Fontana L. Molecular mechanisms of dietary restriction promoting health and longevity. Nat Rev Mol Cell Biol. 2022 Jan;23(1):56-73. doi: 10.1038/s41580-021-00411-4. Epub 2021 Sep 13. PMID: 34518687; PMCID: PMC8692439.
- Hu W, Yang P, Fu Z, Wang Y, Zhou Y, Ye Z, Gong Y, Huang A, Sun L, Zhao Y, Yang T, Li Z, Jiang XC, Yu W, Zhou H. High L-Valine Concentrations Associate with Increased Oxidative Stress and Newly-Diagnosed Type 2 Diabetes Mellitus: A Cross-Sectional Study. Diabetes Metab Syndr Obes. 2022 Feb 19;15:499-509. doi: 10.2147/DMSO.S336736. PMID: 35221701; PMCID: PMC8865866.
- Zhang H, Xiang L, Huo M, Wu Y, Yu M, Lau CW, Tian D, Gou L, Huang Y, Luo JY, Wang L, Song W, Huang J, Cai Z, Chen S, Tian XY, Huang Y. Branched-chain amino acid supplementation impairs insulin sensitivity and promotes lipogenesis during exercise in diet-induced obese mice. Obesity (Silver Spring). 2022 Mar 31. doi: 10.1002/oby.23394. Epub ahead of print. PMID: 35357085.
- Rossi M, Turati F, Strikoudi P, Ferraroni M, Parpinel M, Serraino D, Negri E, La Vecchia C. Dietary intake of branched-chain amino acids and pancreatic cancer risk in a case-control study from Italy. Br J Nutr. 2022 Mar 23:1-19. doi: 10.1017/S0007114522000939. Epub ahead of print. PMID: 35317868.
- Orozco-Ruiz X, Anesi A, Mattivi F, Breteler MMB. Branched-chain and aromatic amino acids related to visceral adipose tissue impact metabolic health risk markers. J Clin Endocrinol Metab. 2022 Mar 23:dgac160. doi: 10.1210/clinem/dgac160. Epub ahead of print. PMID: 35325166
- Green CL, Lamming DW, Fontana L. Molecular mechanisms of dietary restriction promoting health and longevity. Nat Rev Mol Cell Biol. 2022 Jan;23(1):56-73. doi: 10.1038/s41580-021-00411-4. Epub 2021 Sep 13. PMID: 34518687; PMCID: PMC8692439.
- Rivera ME, Rivera CN, Vaughan RA. Branched-chain amino acids at supraphysiological but not physiological levels reduce myotube insulin sensitivity. Diabetes Metab Res Rev. 2022 Feb;38(2):e3490. doi: 10.1002/dmrr.3490. Epub 2021 Aug 24. PMID: 34397159.
- Karadeniz A, Babayiğit E, Görenek PB. Could Branched-Chain Amino Acids Be a New Landmark in Metabolic Syndrome and Cardiac Arrhythmias? Can J Cardiol. 2022 Mar 16:S0828-282X(22)00197-0. doi:10.1016/j.cjca.2022.03.008. Epub ahead of print. PMID: 35306103.
- Cardelo MP, Alcala-Diaz JF, Gutierrez-Mariscal FM, Lopez-Moreno J, Villasanta-Gonzalez A, Arenas-de Larriva AP, Cruz-Ares S, Delgado-Lista J, Rodriguez-Cantalejo F, Luque RM, Ordovas JM, Perez-Martinez P, Camargo A, Lopez-Miranda J. Diabetes Remission Is Modulated by Branched Chain Amino Acids According to the Diet Consumed: From the CORDIOPREV Study. Mol Nutr Food Res. 2022 Feb;66(4):e2100652. doi: 10.1002/mnfr.202100652. Epub 2022 Jan 7. PMID: 34863046.
- Mai K, Cando P, Trasino SE. mTOR1c Activation with the Leucine "Trigger" for Prevention of Sarcopenia in Older Adults During Lockdown. J Med Food. 2022 Feb;25(2):117-120. doi: 10.1089/jmf.2021.0094. Epub 2021 Oct 29. PMID: 34714145
-
The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine. Cell Metabolism. May 4, 2021. Deyang Yu, Nicole E. Richardson, Cara L. Green et al. https://doi.org/10.1016/j.cmet.2021.03.025
- Wang Y, Huang K, Liu F, Lu X, Huang J, Gu D. Association of circulating branched-chain amino acids with risk of cardiovascular disease: A systematic review and meta-analysis. Atherosclerosis. 2022 Jun;350:90-96. doi: 10.1016/j.atherosclerosis.2022.04.026. Epub 2022 Apr 25. PMID: 35576716.
- Santos CS, Nascimento FEL. Isolated branched-chain amino acid intake and muscle protein synthesis in humans: a biochemical review. Einstein (Sao Paulo). 2019;17(3):eRB4898. Published 2019 Sep 5. doi:10.31744/einstein_journal/2019RB4898
-
Wilkinson DJ, Hossain T, Hill DS, et al. Effects of leucine and its metabolite beta-hydroxy-beta-methylbutyrate on human skeletal muscle protein metabolism. J Physiol. June 1, 2013;591(11):2911-2923. doi:10.1113/jphysiol.2013.253203
-
Stephen J. Crozier, Scot R. Kimball, Sans W. Emmert, Joshua C. Anthony, Leonard S. Jefferson. Oral Leucine Administration Stimulates Protein Synthesis in Rat Skeletal Muscle, The Journal of Nutrition, Volume 135, Issue 3, March 2005, Pages 376-382, https://doi.org/10.1093/jn/135.3.376
- Szmelcman S, Guggenheim K. Interference between leucine, isoleucine and valine during intestinal absorption. Biochem J. 1966;100(1):7-11.
- Hyde R, Taylor PM, Hundal HS. Amino acid transporters: roles in amino acid sensing and signalling in animal cells. Biochem J. 2003;373(Pt 1):1-18. Review.
- Wolfe RR. Branched-chain amino acids and muscle protein synthesis in humans: myth or reality? J Int Soc Sports Nutr. 2017;14(1):30
- Churchward-Venne TA, Burd NA, Phillips SM. Nutritional regulation of muscle protein synthesis with resistance exercise: strategies to enhance anabolism. Nutr Metab (Lond). 2012;9(1):40.
- Churchward-Venne TA, Burd NA, Mitchell CJ, West DW, Philp A, Marcotte GR, et al. Supplementation of a suboptimal protein dose with leucine or essential amino acids: effects on myofibrillar protein synthesis at rest and following resistance exercise in men. J Physiol. 2012;590(11):2751-65.
- Churchward-Venne TA, Breen L, Di Donato DM, Hector AJ, Mitchell CJ, Moore DR, et al. Leucine supplementation of a low-protein mixed macronutrient beverage enhances myofibrillar protein synthesis in young men: a double-blind, randomized trial. Am J Clin Nutr. 2014;99(2):276-86.
- Bukhari SS, Phillips BE, Wilkinson DJ, Limb MC, Rankin D, Mitchell WK, et al. Intake of low-dose leucine-rich essential amino acids stimulates muscle anabolism equivalently to bolus whey protein in older women at rest and after exercise. Am J Physiol Endocrinol Metab. 2015;308(12):E1056-65.
-
Audrey Chanet, Sjors Verlaan, Jérôme Salles, Christophe Giraudet, Véronique Patrac, Véronique Pidou, Corinne Pouyet, Nordine Hafnaoui, Adeline Blot, Noël Cano, Nicolas Farigon, Anke Bongers, Marion Jourdan, Yvette Luiking, Stéphane Walrand, Yves Boirie. Supplementing Breakfast with a Vitamin D and Leucine-Enriched Whey Protein Medical Nutrition Drink Enhances Postprandial Muscle Protein Synthesis and Muscle Mass in Healthy Older Men, The Journal of Nutrition, Volume 147, Issue 12, December 2017, Pages 2262-2271, https://doi.org/10.3945/jn.117.252510
- Liberman K, Njemini R, Luiking Y et al. Thirteen weeks of supplementation of vitamin D and leucine-enriched whey protein nutritional supplement attenuates chronic low-grade inflammation in sarcopenic older adults: the PROVIDE study. Aging Clin Exp Res, June 2019;31(6):845-854. doi:10.1007/s40520-019-01208-4
-
Westmead Institute for Medical Research. Muscling in on the role of vitamin D: Research shows vitamin D signaling is needed for normal muscle size and strength. ScienceDaily, 26 June 2019.
www.sciencedaily.com/releases/2019/06/190626125107.htm
-
Amely M Verreijen, Sjors Verlaan, Mariëlle F Engberink, Sophie Swinkels, Johan de Vogel-van den Bosch, Peter JM Weijs. A high whey protein-, leucine-, and vitamin D-enriched supplement preserves muscle mass during intentional weight loss in obese older adults: a double-blind randomized controlled trial. The American Journal of Clinical Nutrition, Volume 101, Issue 2, February 2015, Pages 279-286,
https://doi.org/10.3945/ajcn.114.090290
-
Zheng R, Huang S, Zhu J et al. Leucine attenuates muscle atrophy and autophagosome formation by activating PI3K/AKT/mTOR signaling pathway in rotator cuff tears. Cell Tissue Res 2019. https://doi.org/10.1007/s00441-019-03021-x
- Devries MC, Philips SM, Baker SK et al. Leucine, Not Total Protein, Content of a Supplement Is the Primary Determinant of Muscle Protein Anabolic Responses in Healthy Older Women. The Journal of Nutrition, July 1, 2018.
- Bauer, Jürgen M. et al. Effects of a Vitamin D and Leucine-Enriched Whey Protein Nutritional Supplement on Measures of Sarcopenia in Older Adults, the PROVIDE Study: A Randomized, Double-Blind, Placebo-Controlled Trial. Journal of the American Medical Directors Association, Volume 16, Issue 9, 740-747. September 201
-
Sakiko Abe, Osamu Ezaki, Motohisa Suzuki. Medium-Chain Triglycerides in Combination with Leucine and Vitamin D Increase Muscle Strength and Function in Frail Elderly Adults in a Randomized Controlled Trial. The Journal of Nutrition, Volume 146, Issue 5, May 2016, Pages 1017-1026, https://doi.org/10.3945/jn.115.228965
- Salehpour A, Hosseinpanah F, Shidfar F, et al. A 12-week double-blind randomized clinical trial of vitamin D₃ supplementation on body fat mass in healthy overweight and obese women. Nutr J 2012;11:78. Published 2012 Sep 22. doi:10.1186/1475-2891-11-78
- Chang, Eugene and Kim, Yangha. Vitamin D decreases adipocyte lipid storage and increases NAD-SIRT1 pathway in 3T3-L1 adipocytes. Nutrition 2016, Vol: 32, Issue: 6, Page: 702-8 10.1016/j.nut.2015.12.032
-
Yoshihiro Yoshimura, Takahiro Bise, Fumihiko Takatsuk et al. Effects of a leucine-enriched amino acid supplement on muscle mass,muscle strength, and physical function in post-stroke patients with sarcopenia: A randomized controlled trial. February 2019 Nutrition https://www.sciencedirect.com/science/article/pii/S089990071830594X?via%3Dihub
-
N Yoshii at al. Effect of Mixed Meal and Leucine Intake on Plasma Amino Acid Concentrations in Young Men. Nutrients October 2018, 10(10), 1543; https://doi.org/10.3390/nu10101543
- N Aspell, E Laird, M Healy, B Lawlor, M O’Sullivan. Vitamin D Deficiency Is Associated With Impaired Muscle Strength And Physical Performance In Community-Dwelling Older Adults: Findings From The English Longitudinal Study Of Ageing. October 15, 2019. Clinical Interventions in Aging https://www.dovepress.com/vitamin-d-deficiency-is-associated-with-impaired-muscle-strength-and-p-peer-reviewed-article-CIA