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science nutrition blog

science nutrition <strong>blog</strong>

 By Steve Blechman


Over 70% of Americans are overweight. Medical researchers have projected that by 2030, one in two adults will be obese. Obesity increases the risk for insulin resistance and diabetes. A major health concern!

It has been reported in the scientific research over the years that the branched-chain amino acids isoleucine and valine, but not leucine, are positively associated with increases of insulin resistance, diabetes and obesity in animals as well as humans. In my last article, I reported on a new study published on May 4th, 2021 in the journal Cell Metabolism titled, “The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine.” The researchers found that “reduced isoleucine or valine but not leucine, promotes metabolic health in mice.” Also, that “dietary levels of isoleucine are positively associated with BMI in humans,” and increased obesity in men and women. Also, by specifically reducing isoleucine in the diet, you can improve insulin sensitivity and increase energy expenditure and weight loss. The researchers concluded that results suggest that reducing isoleucine “may be a novel therapeutic and public health strategy to combat the twin epidemics of obesity and diabetes.”

Research has found that the valine catabolite 3-hydroxyisobutyrate (3-HIB) can increase abdominal (visceral) and liver fat as well as muscle fat. And increase insulin resistance (Nature Medicine, April 2016). Leucine has been shown to enhance weight loss in the scientific literature. A new human 24-week randomized controlled trial in 267 adults without diabetes found that leucine combined with sildenafil (Viagra) significantly enhanced weight loss. And when the diabetic drug metformin was added, it enhanced the weight-loss effect at a low dose (Am J Ther, January-February 2021). The weight loss/fat loss benefits of leucine look promising. Further research in humans is needed to confirm leucine’s health, metabolic and weight-loss effects.

The mechanism of action of isoleucine restriction in the diet and weight loss and prevention of diabetes is suggested to be the upregulation action of fibroblast growth factor 21 (FGF-21). FGF-21 is a hormone that promotes insulin sensitivity and enhances thermogenesis, energy expenditure and caloric burning; isoleucine restriction and enhanced FGF-21 facilitates energy expenditure by uncoupled oxidative phosphorylation and conversion of white adipose tissue (WAT) into beige and brown adipose tissue (BAT), known as brown fat.

For the past five years I have written many articles on the health of fat-loss benefits of brown fat. The widely held belief that all body fat is bad is currently being heavily scrutinized, due to the recent discovery of a different type of fat in humans known as brown fat. This type of fat can actually burn off energy in the form of heat by a process known as thermogenesis, which can ultimately reduce overall body fat. The body has two forms of fat: white fat or unwanted fat that can lie directly underneath the skin; and brown fat, which often is found in the shoulder blade region or the neck. Unlike white fat, brown fat is the good fat as it can help burn more calories. The more brown fat you have, the more calories you burn. Brown fat is packed with mitochondria loaded with UCP-1, the protein that uncouples fat burning with ATP (energy) production instead of converting the energy into heat via thermogenesis, making the mitochondria effectively the furnace of the cell. The emergence of brown fat as a readily available fat burning furnace is revolutionary, but like any fire, it requires the proper kindling materials. The ability to get lean by producing extra brown fat, or enhancing the activity of existing brown fat, represents a promising way to burn fat and lose weight.

Several landmark discoveries and approaches to enhancing brown fat function are being explored at major research centers and universities worldwide, with great excitement – including the possible restriction of the branched-chain amino acids isoleucine and valine in the diet and increase of leucine. Over the past seven years I developed THERMO HEAT® – the most scientifically advanced thermogenic brown fat-activating fat burning supplement line ever developed! One of these products is called AML THERMO HEAT FAT BURNING PROTEIN®. It is scientifically designed with low levels of isoleucine and valine and rich in leucine and other brown fat activators to enhance brown fat thermogenesis and help preserve lean body mass during dieting.



1. Yu D, et al. The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine. Cell Metab 2021 Apr 16:S1550-4131(21)00166-2. doi: 10.1016/j.cmet.2021.03.025. Epub ahead of print. PMID: 33887198.

2. Valine Supplementation Does Not Reduce Lipid Accumulation and Improve Insulin Sensitivity in Mice Fed High-Fat Diet. Qinqquan Ma. ACS Omega 2020, 5, 48, 30937-30945. November 23, 2020

3. Fontana L, Cummings NE, Arriola Apelo SI, et al. Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health. Cell Rep 2016;16(2):520-530. doi:10.1016/j.celrep.2016.05.092

4. Alemán G, Castro AL, Vigil-Martínez A, Torre-Villalvazo I, Díaz-Villaseñor A, Noriega LG, Medina-Vera I, Ordáz G, Torres N, Tovar AR. Interaction between the amount of dietary protein and the environmental temperature on the expression of browning markers in adipose tissue of rats. Genes Nutr 2019 Jun 4;14:19. doi: 10.1186/s12263-019-0642-x. PMID: 31178938; PMCID: PMC6549346.

5. Rebello CJ, Zemel MB, Kolterman O, Fleming GA, Greenway FL. Leucine and Sildenafil Combination Therapy Reduces Body Weight and Metformin Enhances the Effect at Low Dose: A Randomized Controlled Trial. Am J Ther. 2021 Jan-Feb 01;28(1):e1-e13. doi: 10.1097/MJT.0000000000001303. PMID: 33369909.

6. Zemel MB, Kolterman O, Rinella M, Vuppalanchi R, Flores O, Barritt AS 4th, Siddiqui M, Chalasani N. Randomized Controlled Trial of a Leucine-Metformin-Sildenafil Combination (NS-0200) on Weight and Metabolic Parameters. Obesity (Silver Spring). 2019 Jan;27(1):59-67. doi: 10.1002/oby.22346. PMID: 30569637.

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10.1152/ajpendo.00241.2019. Epub 2019 Nov 26. PMID: 31770014. 10. Zhang L, Li F, Guo Q, Duan Y, Wang W, Zhong Y, Yang Y, Yin Y. Leucine Supplementation: A Novel Strategy for Modulating Lipid Metabolism and Energy Homeostasis. Nutrients 2020 May 2;12(5):1299. doi: 10.3390/nu12051299. PMID: 32370170; PMCID: PMC7282259.

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14. Fu L, Bruckbauer A, Li F, Cao Q, Cui X, Wu R, Shi H, Zemel MB, Xue B. Leucine amplifies the effects of metformin on insulin sensitivity and glycemic control in diet-induced obese mice. Metabolism. 2015 Jul;64(7):845-56. doi: 10.1016/j.metabol.2015.03.007. Epub 2015 Mar 19. PMID: 25858853.

15. McNeill BT, Suchacki KJ, Stimson RH. Human Brown Adipose Tissue as a Therapeutic Target - Warming up or Cooling Down? Eur J Endocrinol. 2021 Mar 1:EJE-20-1439.R1. doi: 10.1530/EJE-20- 1439. Epub ahead of print. PMID: 33729178.

16. Santhanam, P., Rowe, S.P., Solnes, L.B., Quainoo, B. and Ahima, R.S. (2021), A systematic review of imaging studies of human brown adipose tissue. Ann. N.Y. Acad. Sci..

17. Jang C, Oh SF, Wada S, Rowe GC, Liu L, Chan MC, Rhee J, Hoshino A, Kim B, Ibrahim A, Baca LG, Kim E, Ghosh CC, Parikh SM, Jiang A, Chu Q, Forman DE, Lecker SH, Krishnaiah S, Rabinowitz JD, Weljie AM, Baur JA, Kasper DL, Arany Z. 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. PMID: 26950361; PMCID: PMC4949205.