My Cart

Close

science nutrition blog

science nutrition <strong>blog</strong>

By Steve Blechman

 

Last week, the Centers for Disease Control & Prevention (CDC) said that just being overweight, not obese, can result in severe illness and even death from the coronavirus! Over 70% of Americans are overweight! That is very concerning for so many with COVID-19 and potential health risks.

Recently, scientists have discovered the key to burning fat and calories – a major fat-loss breakthrough! A most recent study published in the journal Cell Metabolism on August 4, 2020 was reported by ScienceDaily on August 5, 2020 that, “an international research team has discovered how to activate brown fat in humans, which may lead to new treatments for type 2 diabetes, and obesity.”

Brown fat can burn off energy in the form of heat by a process known as thermogenesis, which can ultimately reduce overall body fat. This discovery has provided the requisite paradigm shift spawning a new revolution in weight loss that is the primary focus of the book Thermo Heat™ Weight Loss Revolution by Michael J. Rudolph, Ph.D. that includes the foreword by Daniel L. Friedman, MD and Eugene B. Friedman, MD. You can click the link to order on Amazon here and the book is published by Advanced Research Media, Inc. You can also get a free PDF version here

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. Brown fat research is a hot topic today.

The breakthrough study published in the journal Cell Metabolism by Copenhagen researchers and reported in ScienceDaily say that, “Scientists have now discovered that beta2-adrenergic receptors (b2-AR) in brown fat cells are responsible for stimulating thermogenesis. According to Dr. Denis Blondin from CRCHUS, the finding could explain why most clinical trials, which have attempted to induce BAT to burn energy, have performed poorly.”

"In contrast to rodents, human BAT is activated through the stimulation of the beta2-adrenergic receptor, the same receptor responsible for the release of fat from our white adipose tissue."

Researchers in the past thought that beta3-adrenergic-receptors were responsible for activating brown fat cells in humans rather than beta-2-adrenergic receptors. According to Dr. Denis Blondin, one of the clinical investigators of the study, “the finding could explain why most clinical trials, which have attempted to induce BAT to burn energy, have performed poorly.”

Associate Professor Camilla Schéele at CBMR, has said that, "Activation of brown fat burns calories, improves insulin sensitivity and even affects appetite regulation. Our data reveals a previously unknown key to unlocking these functions in humans, which would potentially be of great gain for people living with obesity or type 2 diabetes."

“A second phase of research will begin in the autumn, which will attempt to validate the finding by activating brown fat with drugs that target b2-AR.”

Research has found that exposure to cold temperature (65 degrees Fahrenheit) and consumption of spicy foods such as capsaicin found in chili peppers can activate brown fat. Also, early research has found that caffeine found in coffee has bronchodilating effects (Chest, March 1986). Caffeine is a natural agonist of adrenalin, which can activate b2-AR.

A report appeared on Wednesday, December 18, 2019 in the prestigious New England Journal of Medicine stating that nearly half of American adults will be obese within a decade. The report was led by scientists at Harvard and George Washington Universities. The new research predicts that by 2030, about 50% of U.S. adults will be obese. The Centers for Disease Control and Prevention says that 40% of U.S. adults are obese today.

Recent research published in the Journal of Obesity on July 1, 2020 reported that obesity may be one of the biggest predictors of severe COVID-19 illness. The obesity epidemic is real and upon us – about 4 out of 10 Americans are obese! Obesity or being overweight increases metabolic syndrome, which includes insulin resistance, diabetes, hypertension and cardiovascular disease, which can increase the risk of death in people infected with the coronavirus. Infectious disease experts have said that the coronavirus is going to be around for a while and most likely reoccur in the fall/winter along with the flu.

On May 21, WebMD released data from a poll in which they surveyed 1,012 U.S. readers and found that 47% of women and 22% of men gained weight due to COVID-19 restrictions. This weight gain from the lockdown can have a detrimental effect on your health and well-being.

A most recent study published June 23-30, 2020 in the Journal of the American Medical Association (JAMA) report that 37% of the U.S. population has metabolic syndrome and it’s on the rise! More than 1 billion people have metabolic syndrome globally. It is a worldwide health issue and concern! The metabolic syndrome is mainly caused by obesity and excess body fat around the midsection. Excess abdominal fat and weight gain can increase the risk of inflammation, insulin resistance, elevated blood sugar, diabetes, fatty liver disease, hypertension, and cardiovascular disease.

A healthy diet and lifestyle changes, such as following the Mediterranean Diet along with exercise, has been shown in the scientific research to safely prevent and lower the risk of gaining weight, obesity, metabolic syndrome, diabetes, hypertension, and cardiovascular disease. Many antioxidant foods rich in polyphenols are abundant in the Mediterranean diet such as extra-virgin olive oil, fruits, nuts, red wine, tea, and coffee.

©Published by Advanced Research Media, Inc. 2020

©Reprinted with permission from Advanced Research Media, Inc.

References:

  1. Abdominal Obesity Is Associated with Early All-Cause Mortality Bruce Soloway, MD reviewing Jayedi A et al. BMJ 2020 Sep 23 NEJM https://www.jwatch.org/na52571/2020/10/20/abdominal-obesity-associated-with-early-all-cause

 

  1. Denis P. Blondin, Soren Nielsen, Eline N. Kuipers, Mai C. Severinsen, Verena H. Jensen, Stéphanie Miard, Naja Z. Jespersen, Sander Kooijman, Mariëtte R. Boon, Mélanie Fortin, Serge Phoenix, Frédérique Frisch, Brigitte Guérin, Éric E. Turcotte, François Haman, Denis Richard, Frédéric Picard, Patrick C.N. Rensen, Camilla Scheele, André C. Carpentier. Human Brown Adipocyte Thermogenesis Is Driven by beta2-AR Stimulation. Cell Metabolism, 2020; 32 (2): 287 DOI: 10.1016/j.cmet.2020.07.005

 

  1. University of Copenhagen The Faculty of Health and Medical Sciences. Scientists discover the switch that makes human brown fat burn energy. ScienceDaily, 5 August 2020. www.sciencedaily.com/releases/2020/08/200805102023.htm.

 

  1. Wang Y, Tang C, Tang Y, Yin H, Liu X. Capsaicin has an anti-obesity effect through alterations in gut microbiota populations and short-chain fatty acid concentrations. Food Nutr Res. 2020;64:10.29219/fnr.v64.3525. Published 2020 Feb 19. doi:10.29219/fnr.v64.3525

 

  1. Chili Pepper Consumption and Mortality in Italian Adults. Marialaura Bonaccio, Augusto Di Castelnuovo, Simona Costanzo, Emilia Ruggiero, Amalia De Curtis, Mariarosaria Persichillo, Claudio Tabolacci, Francesco Facchiano, Chiara Cerletti, Maria Benedetta Donati, Giovanni de Gaetano, Licia Iacoviello, on behalf of the Moli-sani Study Investigators. J Am Coll Cardiol. 2019 Dec, 74 (25) 3139-3149.

 

  1. Gong H Jr, Simmons MS, Tashkin DP, Hui KK, Lee EY. Bronchodilator effects of caffeine in coffee. A dose-response study of asthmatic subjects. Chest. 1986;89(3):335-342. doi:10.1378/chest.89.3.335

 

  1. Denova‐Gutiérrez, E., Lopez‐Gatell, H., Alomia‐Zegarra, J.L., López‐Ridaura, R., Zaragoza‐Jimenez, C.A., Dyer‐Leal, D.D., Cortés‐Alcala, R., Villa‐Reyes, T., Gutiérrez‐Vargas, R., Rodríguez‐González, K., Escondrillas‐Maya, C., Barrientos‐Gutiérrez, T., Rivera, J.A. and Barquera, S. (2020), The association between obesity, type 2 diabetes, and hypertension with severe COVID‐19 on admission among Mexicans. Obesity. Accepted Author Manuscript. doi:10.1002/oby.22946

 

  1. Hirode G, Wong RJ. Trends in the Prevalence of Metabolic Syndrome in the United States, 2011-2016. JAMA. 2020;323(24):2526-2528. doi:10.1001/jama.2020.4501

 

  1. More than One-Third of Americans Have Dangerous Metabolic Syndrome. Written by Moira McCarthy on June 26, 2020 - Fact checked by Michael Crescione. Healthline. https://www.healthline.com/health-news/more-than-one-third-of-americans-have-dangerous-metabolic-syndrome

 

  1. Projected U.S. State-Level Prevalence of Adult Obesity and Severe Obesity. The New England Journal of Medicine. Massachusetts Medical Society. Dec 19, 2019. Zachary J. Ward et al. https://www.nejm.org/doi/full/10.1056/NEJMsa1909301

 

  1. Quarantine Weight Gain Not A Joking Matter. Debbie Koenig. WebMD. May 21, 2020. https://www.webmd.com/lung/news/20200521/quarantine-weight-gain-not-a-joking-matter

 

  1. Chao Cao, Qinran Liu, Mohammad Abufaraj, Yunan Han, Tianlin Xu, Thomas Waldhoer, Shahrokh F Shariat, Shengxu Li, Lin Yang, Lee Smith, Regular Coffee Consumption Is Associated with Lower Regional Adiposity Measured by DXA among US Women, The Journal of Nutrition, nxaa121, https://doi.org/10.1093/jn/nxaa121

 

  1. Anglia Ruskin University. Coffee linked to lower body fat in women: Compounds in coffee may have anti-obesity properties. ScienceDaily, 13 May 2020. www.sciencedaily.com/releases/2020/05/200513200402.htm

 

  1. Tverdal A, Selmer R, Cohen JM, Thelle DS. Coffee consumption and mortality from cardiovascular diseases and total mortality: Does the brewing method matter? [published online ahead of print, 2020 Apr 22]. Eur J Prev Cardiol. 2020;2047487320914443. doi:10.1177/2047487320914443

 

  1. Watanabe, M., Risi, R., Tuccinardi, D., Baquero, C.J., Manfrini, S. and Gnessi, L. (2020), Obesity and SARS‐CoV‐2: a population to safeguard. Diabetes Metab Res Rev. Accepted Author Manuscript. doi:10.1002/dmrr.3325

 

  1. Nicastro H, Carvalho.M, Barquilha G, Ferreira LS. Leucine Supplementation: A Possible Anti Inflammatory Strategy Evidences from a Pilot Study. SL Nutr Metab. 2017;1(1):114.

 

  1. Darabi Z, Darand M, Yari Z, et al. Inflammatory markers response to citrulline supplementation in patients with non-alcoholic fatty liver disease: a randomized, double blind, placebo-controlled, clinical trial. BMC Res Notes. 2019;12(1):89. Published 2019 Feb 15. doi:10.1186/s13104-019-4130-6

 

  1. Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent. Alessio Mazzoni, Francesco Annunziato, Lorenzo Cosmi. May 28, 2020. J Clin Invest. 2020. https://doi.org/10.1172/JCI138554.

 

  1. Takeshi Yoneshiro et al. BCAA catabolism in brown fat controls energy homeostasis through SLC25A44. Nature, August 21, 2019 DOI: 10.1038/s41586-019-1503-x

 

  1. Caffeine exposure induces browning features in adipose tissue in vitro and in vivo. Ksenija Velickovic, Declan Wayne, Hilda Anaid Lugo Leija, Ian Bloor, David E. Morris, James Law, Helen Budge, Harold Sacks, Michael E. Symonds & Virginie Sottile. June 24, 2019. Nature Scientific Reports volume 9, Article number: 9104 (6/24/2019)

 

  1. Sara Sloat. Weight Loss Study Reveals Coffee’s Role in Burning One Kind of Body Fat https://www.inverse.com/article/57059-coffee-brown-fat-caffeine-weight-lossInverse.com June 25, 2019

 

  1. Yang YJ, Son HJ, et al. Coffee consumption promotes skeletal muscle hypertrophy and myoblast differentiation. Food Funct 2018, 9, 1102. DOI: 10.1039/C7FO01683B.

 

  1. Wedick N, Mantzoros C, et al. The effects of caffeinated and decaffeinated coffee on sex hormone-binding globulin and endogenous sex hormone levels: a randomized controlled trial. Nutrition Journal, 201211:86 https://doi.org/10.1186/1475-2891-11-86. Wedick et al.; licensee BioMed Central Ltd. 2012 Received June 14, 2012; Accepted October 16, 2012; Published October 19, 2012

 

  1. Symonds, M. E., Aldiss, P., Pope, M. & Budge, H. Recent advances in our understanding of brown and beige adipose tissue: the good fat that keeps you healthy. F1000Res 7, https://doi.org/10.12688/f1000research.14585.1 (2018). 

 

  1. Ouellet, V. et al. Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans. J Clin Invest 122, 545-552, https://doi.org/10.1172/JCI60433 (2012). 

 

  1. van Marken Lichtenbelt, W. D. et al. Cold-activated brown adipose tissue in healthy men. N Engl JMed 360, 1500-1508, https://doi. org/10.1056/NEJMoa0808718 (2009).  

 

  1. Darre, L. & Domene, C. Binding of Capsaicin to the TRPV1 Ion Channel. Mol Pharm 12, 4454-4465, https://doi.org/10.1021/acs. molpharmaceut.5b00641 (2015)  

 

  1. Derbenev, A. V. & Zsombok, A. Potential therapeutic value of TRPV1 and TRPA1 in diabetes mellitus and obesity. Semin Immunopathol 38, 397-406, https://doi.org/10.1007/s00281-015-0529-x (2016). 

 

  1. Luo, Z. et al. TRPV1 activation improves exercise endurance and energy metabolism through PGC-1alpha upregulation in mice. Cell Res 22, 551-564, https://doi.org/10.1038/cr.2011.205 (2012).   

 

  1. Astrup, A. et al. Caffeine: a double-blind, placebo-controlled study of its thermogenic, metabolic, and cardiovascular effects in healthy volunteers. Am J Clin Nutr 51, 759-767, https://doi.org/10.1093/ajcn/51.5.759 (1990). 

 

  1. Yoon M-S. The emerging role of branched-chain amino acids in insulin resistance and metabolism. Forum Nutr, 2016; 8: 405-17.

 

  1. Binder E, Bermudez-Silva FJ, Andre C et al. Leucine supplementation protects from insulin resistance by regulating adiposity levels. PLoS One, 2013; 8:e74705.    

 

  1. Zhang Y, Guo K, LeBlanc RE, Loh D, Schwartz GJ, Yu YH. Increasing dietary leucine intake reduces diet-induced obesity and improves glucose and cholesterol metabolism in mice via multimechanisms. Diabetes, 2007; 56: 1647-54. 

 

  1. Lynch, C.J. and Adams, SH (2014) Branched-chain amino acids in metabolic signaling and insulin resistance. Nat Rev Endrocrinol 10, 723-736. 

 

  1. Xiao, F, Yu, J, Guo, Y, Deng, J, Li, K, et al (2014) Effects of individual branched-chain amino acids deprivation on insulin sensitivity and glucose metabolism in mice. Metabolism 63, 841-850.

 

  1. Jang C, Oh, SF, et al A branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistance. Nat Med 22, 421-426 

 

  1. Lotta LA, Scott RA, Sharp SJ, Burgess S, Luan J, et al. (2016) Genetic Predisposition to an Impaired Metabolism of the Branched-Chain Amino Acids and Risk of Type 2 Diabetes: A Mendelian Randomisation Analysis. PLOS Medicine 13(11): e1002179. https://doi.org/10.1371/journal.pmed.1002179

 

  1. Avogaro, A and Bier, DM (1989.) Contribution of 3-hydroxyisobutyrate to the measurement of 3-hydroxybutyrate in human plasma: comparison of enzymatic and gas-liquid chromatography-mass spectrometry assays in normal and in diabetic subjects. J Lipid Res 30, 1811-1817 

 

  1. Alterations in 3-Hydroxyisobutyrate and FGF21 Metabolism Are Associated With Protein Ingestion–Induced Insulin Resistance Lydia-Ann LS Harris, Gordon I Smith, Bruce W Patterson, Raja S Ramaswamy et al. Diabetes 2017;66:1871-1878 https://doi.org/10.2337/db16-1475

 

  1. Elevated Plasma Levels of 3-Hydroxyisobutyric Acid Are Associated With Incident Type 2 Diabetes Mardinoglu, Adil et al. EBioMedicine, Volume 27, 151-155, Jan. 2018. 

 

  1. Ulrika Andersson-Hall, Carolina Gustavsson, Anders Pedersen, Daniel Malmodin, Louise Joelsson, and Agneta Holmäng. 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.  

 

  1. Macotela, Y Emanuelli, B, Bang, AM et al. (2011) Dietary leucine - an environmental modifier of insulin resistance acting on multiple levels of metabolism. PLoS One 6, e21187. 

 

  1. Increasing Dietary Leucine Intake Reduces Diet-Induced Obesity and Improves Glucose and Cholesterol Metabolism in Mice via Multimechanisms. Y. Zhang, K. Guo, R.E. LeBlanc, D. Loh, G.J. Schwartz, Y. Yu Diabetes Jun 2007, 56 (6) 1647-1654; DOI: 10.2337/db07-0123 

 

  1. Sina S Ullrich, Penelope CE Fitzgerald, Gudrun Schober, Robert E Steinert, Michael Horowitz, Christine Feinle-Bisset; Intragastric administration of leucine or isoleucine lowers the blood glucose response to a mixed-nutrient drink by different mechanisms in healthy, lean volunteers, The American Journal of Clinical Nutrition, Volume 104, Issue 5, 1 November 2016, Pages 1274-1284, https://doi.org/10.3945/ajcn.116.140640.  

 

  1. Li, H, Xu, M, Lee, J, He, C, & Xie, Z (2012). Leucine supplementation increases SIRT1 expression and prevents mitochondrial dysfunction and metabolic disorders in high-fat diet-induced obese mice. American Journal of Physiology - Endocrinology and Metabolism, 303(10), E1234-E1244. http://doi.org/10.1152/ajpendo.00198.2012

 

  1. Kotyczka, C., Boettler, U., Lang, R., Stiebitz, H., Bytof, G., Lantz, I., Hofmann, T., Marko, D. and Somoza, V. (2011), Dark roast coffee is more effective than light roast coffee in reducing body weight, and in restoring red blood cell vitamin E and glutathione concentrations in healthy volunteers. Mol. Nutr. Food Res., 55: 1582-1586. doi:10.1002/mnfr.201100248 

 

  1. Dulloo, A. G., Geissler, C. A., Horton, T., Collins, A. & Miller, D. S. Normal caffeine consumption: influence on thermogenesis and daily energy expenditure in lean and post obese human volunteers. Am J Clin Nutr 49, 44-50, https://doi.org/10.1093/ajcn/49.1.44 (1989). 

 

  1. Kogure, A. et al. Effects of caffeine on the uncoupling protein family in obese yellow KK mice. Clin Exp Pharmacol Physiol 29, 391-394 (2002).

 

  1. Okano, J., Nagahara, T., Matsumoto, K. & Murawaki, Y. Caffeine inhibits the proliferation of liver cancer cells and activates the MEK/ ERK/EGFR signaling pathway. Basic Clin Pharmacol Toxicol 102, 543-551, https://doi.org/10.1111/j.1742-7843.2008.00231.x (2008). 

 

  1. Law, J. et al. Thermal Imaging is a Noninvasive Alternative to PET/CT for Measurement of Brown Adipose Tissue Activity in Humans. J Nucl Med 59, 516-522, https://doi.org/10.2967/jnumed.117.190546 (2018).

 

  1. Yoshioka, K., Yoshida, T., Kamanaru, K., Hiraoka, N. & Kondo, M. Caffeine activates brown adipose tissue thermogenesis and metabolic rate in mice. J Nutr Sci Vitaminol (Tokyo) 36, 173-178 (1990).  

 

  1. Borba GL, Batista JSF, Novais LMQ, et al. Acute Caffeine and Coconut Oil Intake, Isolated or Combined, Does Not Improve Running Times of Recreational Runners: A Randomized, Placebo-Controlled and Crossover Study. Nutrients 2019;11(7):1661. Published 2019 Jul 20. doi:10.3390/nu11071661  

 

  1. Acute effects of three high-fat meals with different fat saturations on energy expenditure, substrate oxidation and satiety. Casas-Agustench, P. et al. Clinical Nutrition, Volume 28, Issue 1, 39-45 2009  

 

  1. The effect of dietary oleic, linoleic, and linolenic acids on fat oxidation and energy expenditure in healthy men. Jones, Peter J.H. et al. Metabolism - Clinical and Experimental, Volume 57, Issue 9, 1198-1203 

 

  1. The influence of the type of dietary fat on postprandial fat oxidation rates: monounsaturated (olive oil) vs saturated fat (cream). LS Piers, KZ Walker, RM Stoney, MJ Soares and K O’Dea. International Journal of Obesity (2002) 26, 814-821 (2002)  

 

  1. Tyler A Churchward-Venne, Leigh Breen, Danielle M Di Donato, Amy J Hector, Cameron J Mitchell, Daniel R Moore, Trent Stellingwerff, Denis Breuille, Elizabeth A Offord, Steven K Baker, Stuart M Phillips, 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

 

  1. Chunzi Liang, Benjamin J Curry, Patricia L Brown and Michael B. Zemel. Leucine Modulates Mitochondrial Biogenesis and SIRT1-AMPK Signaling in C2C12 Myotubes. Journal of Nutrition and Metabolism, vol. 2014, Article ID 239750, 11 pages, 2014. https://doi.org/10.1155/2014/239750.  

 

  1. Impact of 3-week citrulline supplementation on postprandial protein metabolism in malnourished older patients: The Ciproage randomized controlled trial. Bouillanne, Olivier et al. Clinical Nutrition, Volume 38, Issue 2, 564-574. April 2019 

 

  1. Nitric oxide and mitochondrial biogenesis. Enzo Nisoli, Michele O. Carruba. J Cell Sci 2006 119: 2855-2862; doi: 10.1242/jcs.03062 

 

  1. Allerton, T.D.; Proctor, D.N.; Stephens, J.M.; Dugas, T.R.; Spielmann, G.; Irving, B.A. l-Citrulline Supplementation: Impact on Cardiometabolic Health. Nutrients 2018, 10, 921.

 

  1. Yoshitomi H, Momoo M, Ma X, et al. L-Citrulline increases hepatic sensitivity to insulin by reducing the phosphorylation of serine 1101 in insulin receptor substrate-1. BMC Complement Altern Med. 2015;15:188. Published 2015 Jun 18. doi:10.1186/s12906-015-0706-4.  

 

  1. Inflammatory markers response to citrulline supplementation in patients with non-alcoholic fatty liver disease: a randomized, double blind, placebo-controlled, clinical trial. Zahra Darabi, Mina Darand, Zahra Yari, Mehdi Hedayati, Amirhosein Faghihi, Shahram Agah and Azita Hekmatdoost. BMC Research.2019/12:89 https://doi.org/10.1186/s13104-019-4130-6.  

 

  1. Villareal MO, Matsukawa T, Isoda H. L-Citrulline Supplementation-Increased Skeletal Muscle PGC-1alpha Expression is Associated With Exercise Performance and Increased Skeletal Muscle Weight [published online ahead of print, 2018 Jun 25]. Mol Nutr Food Res. 2018;62(14):e1701043. doi:10.1002/mnfr.20170104.  

 

  1. Cliff J. d C. Harvey, Grant M. Schofield, Micalla Williden, and Joseph A. McQuillan. The Effect of Medium Chain Triglycerides on Time to Nutritional Ketosis and Symptoms of Keto-Induction in Healthy Adults: A Randomised Controlled Clinical Trial. Journal of Nutrition and Metabolism, vol. 2018, Article ID 2630565, 9 pages, 2018. https://doi.org/10.1155/2018/2630565.   

 

  1. Li H, Xu M, Lee J, He C and Xie Z. (2012). Leucine supplementation increases SIRT1 expression and prevents mitochondrial dysfunction and metabolic disorders in high-fat diet-induced obese mice. American Journal of Physiology - Endocrinology and Metabolism, 303(10), E1234-E1244. http://doi.org/10.1152/ajpendo.00198.2012

 

  1. Tsuboi T, Maeda M, Hayashi T. Administration of L-arginine plus L-citrulline or L-citrulline alone successfully retarded endothelial senescence. PLoS One. 2018;13(2):e0192252. Published 2018 Feb 7. doi:10.1371/journal.pone.0192252  

 

  1. Miriam E. Clegg (2010) Medium-chain triglycerides are advantageous in promoting weight loss although not beneficial to exercise performance, International Journal of Food Sciences and Nutrition, 61:7, 653-679, DOI: 10.3109/09637481003702114

 

  1. Activation of the AMPK/Sirt1 pathway by a leucine-metformin combination increases insulin sensitivity in skeletal muscle, and stimulates glucose and lipid metabolism and increases life span in Caenorhabditis elegans. Banerjee, Jheelam et al. Metabolism - Clinical and Experimental, Volume 65, Issue 11, 1679-1691. November 2016.  

 

  1. Romero, M. J., Platt, D. H., Caldwell, R. B. and Caldwell, R. W. (2006), Therapeutic Use of Citrulline in Cardiovascular Disease. Cardiovascular Drug Reviews, 24: 275-290. doi:10.1111/j.1527-3466.2006.00275.x

 

  1. Zhang Y, Guo K, LeBlanc RE, Loh D, Schwartz GJ, Yu YH. Increasing dietary leucine intake reduces diet-induced obesity and improves glucose and cholesterol metabolism in mice via multimechanisms. Diabetes 2007; 56: 164754.  

 

  1. Grape seed and skin extract mitigates heart and liver oxidative damage induced by a high-fat diet in the rat: gender dependency. Kamel Charradi, Mohamed Mahmoudi, Salem Elkahoui, Ferid Limam, Ezzedine Aouani. Canadian Journal of Physiology and Pharmacology, 2013, 91:1076-1085, https://doi.org/10.1139/cjpp-2013-0225

 

  1. Dong Hang, Ane Sørlie Kværner, Wenjie Ma, Yang Hu, Fred K Tabung, Hongmei Nan, Zhibin Hu, Hongbing Shen, Lorelei A Mucci, Andrew T Chan, Edward L Giovannucci, Mingyang Song. Coffee consumption and plasma biomarkers of metabolic and inflammatory pathways in US health professionals, The American Journal of Clinical Nutrition, Volume 109, Issue 3, March 2019, Pages 635-647, https://doi.org/10.1093/ajcn/nqy295

 

  1. Joffin N, Jaubert AM, Bamba J, Barouki R, Noirez P, Forest C. Acute induction of uncoupling protein 1 by citrulline in cultured explants of white adipose tissue from lean and high-fat-diet-fed rats. Adipocyte. 2015;4(2):129-34. Published 2015 Jan 7. doi:10.4161/21623945.2014.989748  

 

  1. Joffin, N., Jaubert, A., Durant, S., Bastin, J., De Bandt, J., Cynober, L., Moinard, C., Coumoul, X., Forest, C. and Noirez, P. (2014), Citrulline reduces glyceroneogenesis and induces fatty acid release in visceral adipose tissue from overweight rats. Mol Nutr Food Res, 58: 2320-2330. doi:10.1002/mnfr.201400507  

 

  1. 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:10.1186/1475-2891-11-7   

 

  1. Vitamin D decreases adipocyte lipid storage and increases NAD-SIRT1 pathway in 3T3-L1 adipocytes. Chang, Eugene; Kim, Yangha. Nutrition, 2016, Vol: 32, Issue: 6, Page: 702-8 10.1016/j.nut.2015.12.032 

 

  1. Miriam E. Clegg (2010) Medium-chain triglycerides are advantageous in promoting weight loss although not beneficial to exercise performance, International Journal of Food Sciences and Nutrition, 61:7, 653-679, DOI: 10.3109/09637481003702114 

 

  1. LaBarrie J, St-Onge MP. A coconut oil-rich meal does not enhance thermogenesis compared to corn oil in a randomized trial in obese adolescents. Insights Nutr Metab. 2017;1(1):30-3  

 

  1. Farhat, G., Drummond, S., and Al‐Dujaili, E. A. S. (2017) Polyphenols and Their Role in Obesity Management: A Systematic Review of Randomized Clinical Trials. Phytother. Res., 31: 1005-1018. doi: 10.1002/ptr.5830.  

 

  1. Sugita, J., Yoneshiro, T., Hatano, T., Aita, S., Ikemoto, T., Uchiwa, H., Saito, M. (2013). Grains of paradise (Aframomum melegueta) extract activates brown adipose tissue and increases whole-body energy expenditure in men. British Journal of Nutrition, 110(4), 733-738. doi:10.1017/S0007114512005715  

 

  1. Jun Sugita, Takeshi Yoneshiro, Yuuki Sugishima, Takeshi Ikemoto, Hideyo Uchiwa, Isao Suzuki, Masayuki Saito, Daily Ingestion of Grains of Paradise (Aframomum melegueta) Extract Increases Whole-Body Energy Expenditure and Decreases Visceral Fat in Humans, Journal of Nutritional Science and Vitaminology, 2014, Volume 60, Issue 1, Pages 22-27, Released April 24, 2014. 

 

  1. Hattori, H., Yamauchi, K., Onwona‐Agyeman, S. and Mitsunaga, T. (2018), Identification of vanilloid compounds in grains of paradise and their effects on sympathetic nerve activity. J Sci Food Agric, 98: 4742-4748. doi:10.1002/jsfa.9009 

 

  1. Ross S. Mancini, Yanfei Wang, Donald F. Weaver. Phenylindanes in Brewed Coffee Inhibit Amyloid-Beta and Tau Aggregation. Frontiers in Neuroscience, 2018; 12 DOI: 10.3389/fnins.2018.00735 

 

  1. University Health Network. Drinking coffee may reduce your chances of developing Alzheimer's, Parkinson's. ScienceDaily, 5 November 2018. www.sciencedaily.com/releases/2018/11/181105160825.htm 

 

  1. Ilic NM, Dey M, Poulev AA, Logendra S, Kuhn PE, Raskin I. Anti-inflammatory activity of grains of paradise (Aframomum melegueta Schum) extract. J Agric Food Chem. 2014;62(43):10452-7.  

 

  1. Increment in Dietary Potassium Predicts Weight Loss in the Treatment of the Metabolic Syndrome Brurya Tal, Jessica Sack, Marianna Yaron, Gabi Shefer, Assaf Buch, Limor Ben Haim, Yonit Marcus, Galina Shenkerman, Yael Sofer, Lili Shefer, Miri Margaliot and Naftali Stern. Nutrients June 2,2019, 11(6), 1256; https://doi.org/10.3390/nu11061256.   

 

  1. Cai, X.; Li, X.; Fan, W.; Yu, W.; Wang, S.; Li, Z.; Scott, E.M.; Li, X. Potassium and Obesity/Metabolic Syndrome: A Systematic Review and Meta-Analysis of the Epidemiological Evidence. Nutrients March 25, 2016, 183, 8.   

 

  1. THE THERMO HEAT® LOW-CARB MEDITERRANEAN DIET: WHY IT’S THE HEALTHIEST & BEST DIET FOR 2019 by Steve Blechman, https://advancedmolecularlabs.com/blogs/news/the-thermo-heat%C2%AE-low-carb-mediterranean-diet-why-it-s-the-healthiest-best-diet-for-2019

 

  1. The Thermo Heat® Weight Loss Revolution, by Michael J. Rudolph, Ph.D, including the foreword by Daniel L. Friedman, MD and Eugene B Friedman, MD.