Capsaicin, the Spice For a Longer Life Reduce Fat, Build Muscle and Metabolic Health
By Michael J. Rudolph, Ph.D.
Since time immemorial, man has yearned for the capacity to extend human lifespan. Early explorers, like Ponce de León, actually discovered Florida while fervently searching for the mythical spring known as the Fountain of Youth that allegedly restored the well-being of anyone who drank from or bathed in it. Tales of the search for the Fountain of Youth are also found ubiquitously throughout human history appearing, for instance, in writings as far back in time as the ancient Greek historian Herodotus during the fifth century B.C. Though stories of vitality restoring waters are prevalent throughout human history, attempts to increase human life span have only recently become reality thanks, in part, to modern scientific discovery of molecular compounds that alter certain biochemical and physiological processes in the body, rejuvenating the body and ultimately enhancing the likelihood for a longer life.
Capsaicin, the spicy phytochemical found in chili peppers, belongs to this class of compounds recently discovered to possess an exceptional capacity to extend life span principally by reducing overall body fat levels, providing powerful antioxidant and anti-inflammatory effects, while augmenting insulin action and improving cardiovascular health, which altogether vigorously boost life span. In fact, a pretty recent epidemiological study investigating almost half a million people showed the habitual consumption of chili-rich foods, loaded with capsaicin, reduced the likelihood of death from certain chronic diseases such as cancer and heart disease relative to those who did not consume chili-rich, spicy foods, indicating the aforementioned disease-fighting qualities of capsaicin increase life span.1
Capsaicin Torches Body Fat
The ability of capsaicin to burn body fat is perhaps the most recognized life-extending function of this compound as too much adipose tissue typically promotes chronic inflammation throughout the body, which negatively influences normal bodily function, ultimately shortening life span. Capsaicin robustly promotes fat loss by activating the TRPV1 receptor within the oral cavity, and gastrointestinal tract, triggering release of noradrenaline. The secretion of noradrenaline then stimulates the process of thermogenic-fatty acid oxidation within brown adipose tissue (BAT), which essentially uncouples the normally linked process of fatty acid oxidation with cellular energy production in the form of ATP. Instead, the energy is directly converted into heat, which effectively increases energy expenditure in the end, leading to a leaner body and a longer life.
Several studies looking at the impact of capsaicin on metabolic rate have shown that capsaicin does enhance energy expenditure while boosting fat oxidation, promoting significant weight loss.2 It has also been shown that the positive influence of capsaicin on thermogenesis is greatest in those people with the most BAT, and there is some evidence indicating that sustained intake of capsaicin can increase BAT levels in humans3 , indicating long-term capsaicin intake increases BAT levels, improving the capacity to thermogenically burn body fat.
Different Effects Throughout the Body
Capsaicin binds TRPV1 receptors elsewhere in the body, manifesting some of the antiinflammatory effects associated with capsaicin intake. Yet, counter to capsaicin activation of the TRPV1 receptor that occurs in the oral cavity and gut, capsaicin actually inactivates TRPV1 function in other tissues by overstimulating TRPV1 neurons, causing these neurons to eventually shut down. More specifically, capsaicin shuts down TRPV1-containing neurons that drive defective insulin secretion in diabetic rat models4 , meaning capsaicin ingestion by these diabetic rats actually improves insulin function.5 In fact, capsaicin-laden diets have also been linked to lower incidents of diabetes and metabolic dysregulation in humans as well6 , an outcome that clearly supports longer life as diabetes strongly correlates to shorter life spans. In fact, another study by Riera et al.7 further described the ability of capsaicin to shut down insulin-regulating TRPV1 neurons by directly incubating capsaicin with these insulin-regulating neurons, causing their inactivation. This study also showed mice genetically lacking the TRPV1 receptor lived longer and displayed a more youthful metabolic profile throughout life, further supporting the notion that TRPV1 inactivation in certain tissues can benefit health, resulting in a greater life span.
Improves Cardiovascular Health, Supporting Longer Life
Research has also shown capsaicin improves cardiovascular health by reducing cholesterol levels while concomitantly triggering systemic vasodilation, which together sustains superior cardiovascular health, favoring longevity.
Capsaicin lowers cholesterol levels in the blood in two different ways. The first approach being TRPV1-independent where capsaicin intake increases bile acid production, which improves the capacity to clear cholesterol from the blood, lowering cholesterol levels.8 It has also been shown that capsaicin activation of the TRPV1 receptor in smooth muscle cells lining the arterial wall significantly reduced the accumulation of cholesterol, and other lipids, within the arteries by increasing cholesterol efflux out of these cells while also reducing cholesterol uptake into these cells.9
In addition to its capacity to reduce cholesterol, dietary intake of capsaicin also increases the expression and activity of the enzyme nitric oxide synthase10, resulting in an increase in levels of the signaling molecule nitric oxide (NO) which then stimulated vasodilation, and blood flow, in mice.11 Interestingly, use of the capsaicin patch during this study increased serum NO, which improved blood flow to the working muscles and heart for improved overall exercise performance that will clearly increase the odds of living a healthier and longer life.
Antioxidant and Anti-inflammatory Effects Diminish Disease
Another positive impact capsaicin has on overall wellness and an increased life span is the exceptional capacity of this compound to uncouple macronutrient oxidation with energy production throughout the body. While this capability can be used to increase energy expenditure by thermogenesis in BAT providing its own life-extending effect, as previously mentioned, in other tissues such as the liver and heart, the uncoupling of energy production to the oxidation of fats and carbohydrates can also increase life span by reducing the production of superoxide free radicals that are normally produced by this process. This is particularly the case when oxidation rates are very high, overwhelming the oxidative machinery within the cell and ultimately resulting in greater levels of superoxide free radical production.12-13 The reduction of superoxide free radical levels within these tissues diminishes the amount of free radical damage to life-sustaining biomolecules required for normal cellular function, such as DNA, which causes them to malfunction, promoting the disease state and ultimately reducing life span. The accumulation of oxidative damage from these superoxide free radicals also stimulates a devastating immune response that leads to chronic inflammation, further promoting the disease state and premature death.14-15 Consequently, the ability of capsaicin to extinguish free radical damage diminishes oxidative damage to key biomolecules, reducing long-term inflammation and thus the development of chronic disease, ultimately extending life.
Capsaicin Prevents Age-related Muscle Loss
Another life-extending quality of capsaicin stems from the ability of this compound to antagonize muscle loss while promoting muscle growth. The loss of muscle tissue throughout life unquestionably reduces life span due to loss of mobility, which promotes inactivity, perhaps the most important parameter that shortens life span. After age 30, one typically begins to lose muscle mass and function due to age-related sarcopenia. The loss of muscle mass for physically inactive people can be as high as 5 percent per decade after age 30. Active individuals also have some muscle loss though to a lesser extent. The reversal of muscle loss from capsaicin will antagonize age-related muscle loss, supporting longevity.
Activation of TRPV1 by capsaicin in muscle tissue enhances, and maintains, muscle size. The positive influence on muscle mass from capsaicin intake was demonstrated in a study by Ito et al.16 In this study, both capsaicin and synergistic ablation – a process that destroys a synergistic muscle group, putting more strain on the targeted muscle group, driving the targeted muscle to adapt and grow – increased the mass of the targeted plantaris leg muscle to a similar degree. Capsaicin also enhanced muscular force production within another group of leg muscles, suggesting that capsaicin can increase muscular strength as well as muscular size. Interestingly, the positive impact of capsaicin on muscle growth was caused by activating the enzyme mTOR. Activation of mTOR is well known to increase muscle protein synthesis and therefore muscle growth.17-19 However, the exact mechanism by which capsaicin activates mTOR was largely unknown until this recent investigation by Ito et al.16 where they revealed that capsaicin activation of TRPV1 causes an increase in intracellular calcium within the muscle cell that turns on mTORdriven muscle protein synthesis.
In addition to capsaicin increasing muscle size and strength, this compound also importantly inhibits muscular atrophy. Muscular atrophy occurs when muscle protein degradation exceeds muscle protein synthesis, lowering muscle protein levels and therefore muscle size. The loss of muscle mass caused by muscular atrophy can be counteracted by increasing protein synthesis or inhibiting protein degradation. Capsaicin apparently mitigates muscle atrophy by doing both as capsaicin increases mTOR-driven muscle protein synthesis as previously mentioned, while also reducing muscle protein degradation.
In the previously mentioned study by Ito et al.16, researchers showed capsaicin intake completely prevented the decrease of muscle weight and fiber size in both the soleus and gastrocnemius leg muscles after the mice in this study had their hind limbs suspended for one week, while a second group that did not take capsaicin showed decreases in muscle mass of 34 percent and 16 percent in their soleus and gastrocnemius muscle, respectively. The authors of this study hypothesized that the activation of mTOR likely stimulates function of the molecule PGC-1alpha, which has been shown in other studies20 to reduce muscle protein degradation when activated, meaning the enhancement of PGC-1alpha function by mTOR would reduce muscle protein degradation. Interestingly, increased expression of PGC-1alpha from capsaicin use has also been shown to increase the expression of genes involved in fatty acid oxidation, promote mitochondrial biogenesis, and enhance exercise endurance, which altogether will most assuredly elongate one's life span.20
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 biological effects of exercise as a fellow at Harvard Medical School and Columbia University. 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 Senior Scientist working at the New York Structural Biology Center where he investigates the molecular nature of human illness and disease.
© Published by Advanced Research Media, Inc. 2021
© Reprinted with permission from Advanced Research Media, Inc.
1. Lv J, Qi L, Yu C, et al. Consumption of spicy foods and total and cause specific mortality: population based cohort study. Bmj (2015); 351, h3942.
2. Ludy MJ, Moore GE and Mattes RD. The effects of capsaicin and capsiate on energy balance: critical review and meta-analyses of studies in humans. Chem Senses 37, 103-121.
3. Yoneshiro T, Aita S, Kawai Y, et al. Nonpungent capsaicin analogs (capsinoids) increase energy expenditure through the activation of brown adipose tissue in humans. Am J Clin Nutr 95, 845-850.
4. Gram DX, Ahren B, Nagy I, et al. Capsaicin-sensitive sensory fibers in the islets of Langerhans contribute to defective insulin secretion in Zucker diabetic rat, an animal model for some aspects of human type 2 diabetes. Eur J Neurosci 2007; 25, 213-223.
5. Gram DX, Hansen AJ, Wilken M, et al. Plasma calcitonin gene-related peptide is increased prior to obesity, and sensory nerve desensitization by capsaicin improves oral glucose tolerance in obese Zucker rats. Eur J Endocrinol 2005; 153, 963-969.
6. Westerterp-Plantenga MS, Smeets A and Lejeune MP. Sensory and gastrointestinal satiety effects of capsaicin on food intake. Int J Obes 2005 (Lond) 29, 682-688.
7. Riera CE, Huising MO, Follett P, et al. TRPV1 pain receptors regulate longevity and metabolism by neuropeptide signaling. Cell 157, 1023-1036.
8. Huang W, Cheang WS, Wang X, et al. Capsaicinoids but not their analogue capsinoids lower plasma cholesterol and possess beneficial vascular activity. J Agric Food Chem 62, 8415- 8420.
9. Ma L, Zhong J, Zhao Z, et al Activation of TRPV1 reduces vascular lipid accumulation and attenuates atherosclerosis. Cardiovasc Res 92, 504-513.
10. Lo YC, Hsiao HC, Wu DC, et al. A novel capsaicin derivative VOA induced relaxation in rat mesenteric and aortic arteries: involvement of CGRP, NO, cGMP, and endothelium-dependent activities. J Cardiovasc Pharmacol 2003; 42, 511-520.
11. Yang D, Luo Z, Ma S, et al. Activation of TRPV1 by dietary capsaicin improves endothelium-dependent vasorelaxation and prevents hypertension. Cell Metab 12, 130-141.
12. Negre-Salvayre A, Hirtz C, Carrera G, et al. A role for uncoupling protein-2 as a regulator of mitochondrial hydrogen peroxide generation. Faseb J 1997; 11, 809-815.
13. Echtay KS, Roussel D, St-Pierre J, et al. Superoxide activates mitochondrial uncoupling proteins. Nature 2002; 415, 96-99.
14. Haffner SM. The metabolic syndrome: inflammation, diabetes mellitus, and cardiovascular disease. Am J Cardiol 2006; 97, 3A-11A.
15. Lin WW and Karin M. A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest 2007; 117, 1175-1183.
16. Ito N, Ruegg UT, Kudo A. Activation of calcium signaling through Trpv1 by nNOS and peroxynitrite as a key trigger of skeletal muscle hypertrophy. Nat Med 2013; 19, 101-106.
17. Bodine SC, Stitt TN, Gonzalez M, et al. Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat Cell Biol 2001; 3, 1014- 1019.
18. Goodman CA, Miu MH, Frey JW. A phosphatidylinositol 3-kinase/protein kinase B independent activation of mammalian target of rapamycin signaling is sufficient to induce skeletal muscle hypertrophy. Mol Biol Cell 2010; 21, 3258-3268.
19. Hornberger TA, Stuppard R, Conley KE, et al. Mechanical stimuli regulate rapamycin sensitive signalling by a phosphoinositide 3-kinase-, protein kinase B- and growth factor independent mechanism. Biochem J 2004; 380, 795-804.
20. Luo Z, Ma, L, Zhao Z, et al. TRPV1 activation improves exercise endurance and energy metabolism through PGC-1alpha upregulation in mice. Cell Res 2012; 22, 551-564.