My Cart

Close

science nutrition blog

science nutrition <strong>blog</strong>

 By Steve Blechman

 

A new review article entitled “Branched Chain Amino Acids And Cardiovascular Disease” was published in the prestigious journal Nature Reviews Cardiology in February 2023. Researchers from Duke University School of Medicine reported that “high-circulating concentrations of BCAA are a hallmark of metabolic disorders, including obesity, insulin resistance and type 2 diabetes mellitus.”

“Epidemiological studies have also shown that high plasma BCAA concentrations identify individuals with heart failure, coronary artery disease or hypertension and predict adverse events in these populations.” The review article discussed key points such as “the roles of impaired BCAA metabolism in vascular function and arteriosclerosis.”

The potential mechanism of action of BCAA metabolism and cardiovascular disease include impaired vascular relaxation, reactive oxygen species (ROS) generation, BCAA oxidation in platelets promoting thrombosis, and the valine-derived metabolite three-hydroxybutyrate (3-HiB).

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.”

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.

“In support of an anti-atherogenic role for BCAAs, adding leucine to the drinking water” of mice decreases LDL cholesterol and “50% reduction in aortic atherosclerotic plaque.” Also, the review says “elevated leucine levels” were associated with the decreased risk of coronary artery disease in the “Jackson heart study a population study” composed of African American individuals.

In 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.

THE BEST LEUCINE SUPPLEMENT

AML Post Workout contains 5 grams of pure leucine. It also contains 5 grams of creatine monohydrate and 2.5 grams of betaine. Creatine has been reported in the scientific literature to function as a myostatin inhibitor, supporting muscle growth. Betaine has also been found in the scientific research to stimulate growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Combining 5 grams of pure leucine along with 5 grams of creatine monohydrate and 2.5 grams of betaine makes AML Post Workout a potent muscle growth and recovery supplement. For best results, we suggest taking one serving of AML Post Workout by itself (on an empty stomach) 15-30 minutes before a post-workout meal, providing all the essential amino acids required for muscle protein synthesis.

 

References:

  1. McGarrah, R.W., White, P.J. Branched-chain amino acids in cardiovascular disease. Nat Rev Cardiol 20, 77-89 (2023) Feb 2023. https://doi.org/10.1038/s41569-022-00760-3
  2. Zhang Y, Duan Y, Jiang M, He X, Xu S, Guo J, Li M, Zhou C, Wu D, Liu G, Ji X. Branched-chain amino acids and risk of stroke: A Mendelian randomization study. Front Neurosci. 2023 Feb 9;17:1143718. doi: 10.3389/fnins.2023.1143718. PMID: 36845444; PMCID: PMC9947500.
  3. Zhang C, Wang S, Wu Y, Guo Y, Wang X. Baseline Serum BCAAs are Related to the Improvement in Insulin Resistance in Obese People After a Weight Loss Intervention. Diabetes Metab Syndr Obes. 2023 Jan 19;16:179-186. doi: 10.2147/DMSO.S388117. PMID: 36760594; PMCID: PMC9869786.
  4. Yeh CY, Chini LCS, Gallagher MS, Davidson JW, Freichels IT, Calubag MF, Rodgers AC, Green CL, Babygirija R, Sonsalla MM, Pak HH, Trautman M, Hacker TA, Simcox J, Lamming DW. Restricting dietary protein or dietary isoleucine improves metabolic health in aged mice. bioRxiv [Preprint]. 2023 Feb 7:2023.02.06.527311. doi: 10.1101/2023.02.06.527311. PMID: 36798157; PMCID: PMC9934591.
  5. Circulating Branched-Chain Amino Acids, Incident Cardiovascular Disease, and Mortality in the African American Study of Kidney Disease and Hypertension. Shengyuan Luo, MBBS, MHS, Aditya Surapaneni, PhD, Casey M. Rebholz, PhD, MS, MNSP, MPH, Lawrence J. Appel, MD, MPH, Josef Coresh, MD, PhD, Morgan E. Grams, MD, PhD.
  6. 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.
  7. 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
  8. 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
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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
  20. 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
  21. 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.
  22. Yang Zhao, et al. Leucine supplementation via drinking water reduces atherosclerotic lesions in apoE null mice. Acta Pharmacol Sin 2016 Feb;37(2):196-203. doi: 10.1038/aps.2015.88. Epub 2015 Dec 21.
  23. Cholsoon Jang, et al. A branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistance. Nat Med 2016 Apr;22(4):421-6. doi: 10.1038/nm.4057. Epub 2016 Mar 7.