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TOP 10 THERMOGENIC AND BROWN FAT ACTIVATORS

advancedmolecularlabs Admin

Posted on December 18 2017

Lose Your Gut: Top 10 Thermogenic and Brown Fat Activators

By Michael J. Rudolph, Ph.D.

The nutritional supplement world has seen its fair share of “fat-burning” products claiming to be able to reduce body fat by simply increasing the rate at which fat is oxidized, or burned, within the body. While this approach to a leaner body seems pretty logical, it has one major drawback— as increasing the level of fatty acid oxidation simply results in the production of more of the energy-rich molecule ATP— which, at first glance, may not seem problematic. However, higher levels of ATP do not reduce body fat. In fact, what it will do is trigger homeostatic mechanisms within the body that will simply convert this ATP surplus back into body fat within a rather short period of time. So, the fundamental problem with merely converting body fat into ATP is that this process does not increase the amount of energy expenditure— which is the only valid way to reduce body fat.

Recent attempts to advance fat loss by explicitly boosting energy expenditure have included the use of several naturally occurring compounds that target brown adipose tissue, or brown fat. This type of fat, despite being fat itself, has the unique capacity to reduce the other type of fat, white adipose tissue, which is usually referred to as body fat. Brown fat minimizes body fat by activating a process known as thermogenesis that increases energy expenditure— which, once again, is essential to minimize body fat.

Brown fat is able to increase energy expenditure because it contains a different type of fat cell that uncouples fat burning with ATP production, converting the energy from fatty acid oxidation into heat instead. Most cells within the body can perform thermogenesis to varying degrees. However, brown fat performs thermogenesis most effectively— as each brown fat cell has more fat-incinerating mitochondria that possess a higher concentration of the UCP-1 protein that is directly responsible for the thermogenic function of uncoupling fat oxidation with ATP production. As a result, brown fat has a greater capacity than any other cell in the body to thermogenically burn more fat and uncouple this process to energy production, ultimately increasing energy expenditure and fat loss.

Thermogenesis in brown fat is typically triggered by exposure to cold temperatures, as thermogenically derived heat can be used to warm up the body. Cold temperatures stimulate the TRPV receptor within the brain, which triggers the sympathetic nervous system, resulting in the release of noradrenaline. The subsequent interaction between adrenaline and the beta-adrenergic receptors embedded within the cellular membranes of brown fat initiates uncoupled fatty acid oxidation or thermogenesis, generating heat. While prolonged exposure to cold temperatures for roughly two hours has been shown to effectively trigger brown fat activity and fat loss1, using this approach to lower body fat is rather impractical, based on the considerable amount of time necessary to trigger the fat-burning capacity of brown fat.

Many studies have shown that other members of the TRPV family are activated outside of the brain by various food-related compounds, instead of cold temperatures. Some of these compounds bind directly to TRPV receptors within the oral cavity, similarly activating the sympathetic nervous system and stimulating the thermogenic process within brown fat. Other compounds have been identified that also induce brown fat thermogenesis, either by directly stimulating noradrenaline release or activating the adrenergic receptors within brown fat. Several other thermogenic compounds have been identified that more directly enhance the functional capacity of brown fat by increasing UCP-1 production within the cell, effectively improving the thermogenic process. Since all of these compounds remove the requirement for prolonged cold exposure, they represent a much more practical way to generate thermogenic-driven fat loss.

There are many different compounds that trigger thermogenesis, with some being much more effective than others. So, after countless hours of scouring through the science, we’ve compiled a list of the top 10 thermogenic supplements that potently increase energy expenditure, giving an uncommon ability to burn fat and keep if off. Green tea extract containing concentrated catechins is not recommended in this review, because of possible liver toxicity!

  1. Caffeine Raises Your Thermogenic Buzz

Caffeine is best known as the active ingredient in coffee that stimulates the central nervous system, impeding drowsiness and restoring alertness. Caffeine is also a potent thermogenic compound. In fact, a single dose of 100 milligrams of caffeine can increase thermogenically driven energy expenditure by approximately 100 calories per day2, demonstrating that regularly ingested doses of caffeine can have a significant influence on energy balance and fat loss.

  1. P-Synephrine (from Citrus aurantium) Safely Boosts Thermogenic Fat Loss

P-Synephrine is an alkaloid found in bitter orange and other citrus fruits including oranges and grapefruits3, and is widely used for weight management. Studies show that P-synephrine specifically binds to beta-3 adrenergic receptors found in brown fat.4 This class of adrenergic receptor explicitly activates thermogenesis within brown fat. In line with this finding, P-synephrine has been shown to elicit a thermogenic effect by increasing resting metabolic rate in humans, with no adverse impact on heart rate or blood pressure, which typically occurs by activating the beta-1 and beta-2 adrenergic receptors.5

  1. Dopamine Activators: Tyrosine and L-Dopa (from Mucuna pruriens) Drive Thermogenesis

Consumption of the dopamine precursors tyrosine and L-Dopa increases dopamine production and function.6,7,8 The neurotransmitter dopamine regulates neurons that initiate the thermogenic process. In fact, energy expenditure was shown to increase in subjects infused with dopamine in a dose-dependent manner, where greater levels of dopamine increased the amount of energy expenditure.9 Consequently, the capability of tyrosine and L-Dopa to increase dopamine levels should produce a robust thermogenic effect, supporting considerable fat loss.

  1. Ursolic Acid Increases BAT Levels for Enhanced Thermogenesis

Another powerful approach that exploits the thermogenic potential of brown fat involves increasing the amount of brown fat in the body. A compound found in many fruits and herbs, known as ursolic acid, has recently been shown to increase brown fat levels.10 Ursolic acid has also been shown to increase the expression of UCP-1, effectively increasing the thermogenic capacity of brown fat. This combined action gives ursolic acid the unique capacity to increase both the activity and quantity of brown fat, providing an extraordinary capacity to increase thermogenically driven energy expenditure and considerable fat loss.

  1. Bile Acids Activate Thermogenesis by Stimulating Thyroid Hormone Activity

Bile acids typically emulsify fat for improved digestion. The use of bile acids as a supplement also provides resistance to diet-induced obesity by upregulating thyroid hormone function, which boosts thermogenesis in brown fat.11 More precisely, bile acids have the capacity to bind to the TGR-5 receptor embedded in the cellular membrane of brown fat. The interaction between bile acids and the TGR-5 receptor escalates the expression of the enzyme deiodinase, which catalyzes the production of the active thyroid hormone triiodothyronine or T3. Greater T3 results in the stimulation of UCP-1 production, which enhances brown fat thermogenesis.

  1. Kaempferol and 7. Oleuropein – Polyphenols That Improve Thyroid Function and Fat Burning

A wide variety of polyphenolic compounds also enhance thermogenic fat loss. One of the more potent being oleuropein, a polyphenolic found in extra-virgin olive oil, which can enhance noradrenaline secretion and increase UCP-1 in brown fat, triggering thermogenesis.12 Another polyphenolic with remarkable thermogenic properties isolated from different sources such as tea, broccoli and grapefruit is the compound kaempferol. This compound uniquely activates the thermogenic process in muscle cells. All cells have the capacity to burn fat and expend energy via thermogenesis. Kaempferol also stimulates thyroid hormone production, which stimulates thermogenesis in brown fat13, giving kaempferol the unusual capability to activate thermogenesis in different cell types within the body, which most certainly contributes to its robust fat-scorching capacity.

  1. Spices: Capsaicin, Piperine, Ginger (Gingerols), Cinnamon (Cinnamaldehyde)

Capsaicin is the spice found in chili peppers that contributes to the hot and spicy flavor of the chili pepper. Capsaicin directly binds and activates the TRPV1 receptor within the oral cavity— which releases noradrenaline, boosting thermogenesis in brown fat. Several studies have shown that a single ingestion of capsaicin can activate brown fat thermogenesis14,15, while longer term ingestion of roughly six weeks increased thermogenesis in brown fat, resulting in reduced body fat.16 Interestingly, this six-week study also showed thermogenic activity in brown fat contributed significantly to fat loss in individuals who had an extremely low amount of brown fat before the study began, which strongly suggests that long-term intake of capsaicin can also increase the amount of brown fat in the body.

Three more spices— piperine, the spicy compound from black pepper; cinnamaldehyde, the pungent ingredient in cinnamon; and gingerol, the active constituent in ginger— also strongly induce thermogenic fat loss. Like capsaicin, piperine and gingerol activate the TRPV1 receptor while cinnamaldehyde activates the TRPA1 receptor, a member within the TRPV1 family of receptors. Activation of this family of receptors triggers thermogenic energy expenditure in a similar fashion to capsaicinoids17,18, which ultimately depletes body fat in a similarly powerful way. For best results, take quick-release supplements of capsaicin. Coated or delayed-release capsaicin may not be as effective because they bypass TRPV1 receptors in the stomach and upper gastrointestinal tract.

  1. Forskolin (from Coleus forskohlii)

Forskolin is a chemical produced by the Indian coleus plant that activates the enzyme adenylyl cyclase within brown fat, resulting in greater cyclic AMP (cAMP) levels. Increased levels of cAMP in brown fat cells also occur when noradrenaline binds to the beta-adrenergic receptor, triggering thermogenesis. Therefore, the ability of forskolin to increase cAMP levels in brown fat also enhances thermogenesis. In fact, it has been reported that hamsters and rats given forskolin increased oxygen consumption and thermogenic activity of brown fat.19 Furthermore, forskolin does not interact with beta-receptors in brown fat cells like noradrenaline does20, indicating that forskolin could have an additive impact on thermogenesis when taken with other thermogenic compounds that directly trigger noradrenaline release and beta-adrenergic production of cAMP— producing superior levels of thermogenic fat loss.

  1. Melatonin

Melatonin is a hormone secreted by the pineal gland in the brain that regulates the sleep/wake cycle, helping you fall asleep. Melatonin is also involved in energy metabolism and bodyweight control. Many studies show that melatonin reduces bodyweight and abdominal fat21 without eating less or increasing physical activity. Conceivably, melatonin reduces fat without decreasing food consumption or physical activity by activating thermogenesis in brown fat22, which increases energy expenditure and thus fat loss.

For most of Michael Rudolph’s career he has been engrossed in the exercise world as either an athlete (he played college football at Hofstra University), personal trainer or as a research scientist (he earned a B.Sc. in Exercise Science at Hofstra University and a Ph.D. in Biochemistry and Molecular Biology from Stony Brook University). After earning his Ph.D., Michael investigated the molecular biology of exercise as a fellow at Harvard Medical School and Columbia University for over eight years. That research contributed seminally to understanding the function of the incredibly important cellular energy sensor AMPK— leading to numerous publications in peer-reviewed journals including the journal Nature. Michael is currently a scientist working at the New York Structural Biology Center doing contract work for the Department of Defense on a project involving national security.

References:

 1. Yoneshiro T, Aita S, et al. Brown adipose tissue, whole-body energy expenditure, and thermogenesis in healthy adult men. Obesity (Silver Spring) 2011;19, 13-16.

2. Dulloo AG, Geissler CA, et al. Normal caffeine consumption: influence on thermogenesis and daily energy expenditure in lean and postobese human volunteers. Am J Clin Nutr 1989;49, 44-50.

3. Nelson BC, Putzbach K, et al. Mass spectrometric determination of the predominant adrenergic protoalkaloids in bitter orange (Citrus aurantium). J Agric Food Chem 2007;55, 9769-9775.

4. Shannon JR, Gottesdiener K, et al. Acute effect of ephedrine on 24-h energy balance. Clin Sci (Lond) 1999;96, 483-491.

5. Stohs SJ, Preuss HG, et al. Effects of p-synephrine alone and in combination with selected bioflavonoids on resting metabolism, blood pressure, heart rate and self-reported mood changes. Int J Med Sci 2015;8, 295-301.

6. Hull KM and Maher TJ. Effects of L-tyrosine on mixed-acting sympathomimetic-induced pressor actions. Pharmacol Biochem Behav 1992;43, 1047-1052.

7. Tharakan B, Dhanasekaran M, et al. Anti-Parkinson botanical Mucuna pruriens prevents levodopa induced plasmid and genomic DNA damage. Phytother Res 2007;21, 1124-1126.

8. Katzenschlager R, Evans A, et al. Mucuna pruriens in Parkinson's disease: a double blind clinical and pharmacological study. J Neurol Neurosurg Psychiatry 2004;75, 1672-1677.

9. Ruttimann Y, Schutz Y, et al. Thermogenic and metabolic effects of dopamine in healthy men. Crit Care Med 1991;19, 1030-1036.

10. Kunkel SD, Elmore CJ, et al. Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease. PLoS One 2012;7, e39332.

11. Watanabe M, Houten SM, et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature 2006;439, 484-489.

12. Oi-Kano Y, Kawada T, et al. Oleuropein, a phenolic compound in extra virgin olive oil, increases uncoupling protein 1 content in brown adipose tissue and enhances noradrenaline and adrenaline secretions in rats. J Nutr Sci Vitaminol (Tokyo) 2008;54, 363-370.

13. da-Silva WS, Harney JW, et al. The small polyphenolic molecule kaempferol increases cellular energy expenditure and thyroid hormone activation. Diabetes 2007;56, 767-776.

14. Yoneshiro T, Aita S, et al. Nonpungent capsaicin analogs (capsinoids) increase energy expenditure through the activation of brown adipose tissue in humans. Am J Clin Nutr 2012;95, 845-850.

15. Saito M and Yoneshiro T. Capsinoids and related food ingredients activating brown fat thermogenesis and reducing body fat in humans. Curr Opin Lipidol 2013;24, 71-77.

16. Yoneshiro T, Aita S, et al. Recruited brown adipose tissue as an antiobesity agent in humans. J Clin Invest 2013;123, 3404-3408.

17. Yoneshiro T and Saito M. Transient receptor potential activated brown fat thermogenesis as a target of food ingredients for obesity management. Curr Opin Clin Nutr Metab Care 2013;16, 625-631.

18. McNamara FN, Randall A and Gunthorpe MJ. Effects of piperine, the pungent component of black pepper, at the human vanilloid receptor (TRPV1). Br J Pharmacol 2005;144, 781-790.

19. Scarpace PJ and Matheny M. Thermogenesis in brown adipose tissue with age: post-receptor activation by forskolin. Pflugers Arch 1996;431, 388-394.

20. Zhao J, Cannon B and Nedergaard J. alpha1-Adrenergic stimulation potentiates the thermogenic action of beta3-adrenoreceptor-generated cAMP in brown fat cells. J Biol Chem 1997;272, 32847-32856.

21. Wolden-Hanson T, Mitton DR, et al. Daily melatonin administration to middle-aged male rats suppresses body weight, intraabdominal adiposity, and plasma leptin and insulin independent of food intake and total body fat. Endocrinology 2000;141, 487-497.

22. Tan DX, Manchester LC, et al. Significance and application of melatonin in the regulation of brown adipose tissue metabolism: relation to human obesity. Obes Rev 2011;12, 167-188.