Resveratrol

Resveratrol is a polyphenolic plant nutrient that research suggests may possess anti-inflammatory and antioxidant attributes. 

For centuries, Japanese and Chinese medicinal traditions have utilized resveratrol to treat a variety of  ailments. Many in the scientific community postulate that the high resveratrol in red wine could help explain the “French Paradox”: the phenomenon in which the French have relatively low incidence of cardio vascular disease but have a diet relatively high in animal products and saturated fat.

How Does Resveratrol Help Promote Musculoskeletal Health*?

There are similar biologic and physiologic processes that drive tendon, muscle, bone and joint aging. Research suggests oxidative stress, chronic inflammation, and mitochondrial dysfunction contribute to unhealthy aging of tendons, muscles, bones, and joints.

Oxidative stress occurs when the production of destructive free radicals overwhelms the body’s natural defenses against oxidation. In this scenario, free radicals roam unfettered attacking healthy fats, healthy proteins, and healthy DNA. 

Chronic inflammation leads to the up regulation of certain chemicals and enzymes that cause significant collateral damage to healthy structures. This damage causes cellular dysfunction and pre mature aging.

Mitochondrial dysfunction increases the number of free radicals generated in the cell. Too many free radicals perpetuate and fuel oxidative stress and chronic inflammation.

Additionally, mitochondria are the primary power generates of the cell. Mitochondrial dysfunction reduces the energy available to cells. Optimal energy is fundamental for healthy cellular function.  Cells, just like cars, don’t work without fuel.

Resveratrol supports joint, muscle, and tendon health by counteracting certain aspects of the pathways that lead to unhealthily aging and cellular dysfunction.

Resveratrol possesses a unique chemical structure that allows it both to donate and to except electrons. In either situation, resveratrol remains relatively stable. Resveratrol’s stability in differing electron states is its critical contribution to antioxidant protection. The primary problem with free radicals are their high reactivity when they have too many or too little electrons. Resveratrol can both offload  excess electrons or donate additional electrons to free radicals. Stabilized free radicals are less likely to attack surrounding tissue.

Free radical stabilization is especially important when protecting mitochondrial cell walls and healthy fats.  Healthy fats are hyper sensitive to oxidative damage. Fat oxidation punctures holes in the cell wall and leads to leaks. A leaky mitochondria releases excessive oxygen based free radicals and compromises healthy mitochondrial function. Resveratrol potentially helps prevent holes from forming in the mitochondria wall  and helps promote mitochondrial well being.

Additionally, resveratrol  may stimulate the activity Sirtuin 1. Sirtuin 1 is a vital protein that influences inflammation, longevity, mitochondrial function, and oxidative stress. The overall effect of Sirtulin 1 is to promote a healthy immune system response to healing, promote mitochondrial health, and promote robust anti-oxidant defenses.

Musculoskeletal Benefits of Resveratrol*

1.  Supports Joint Health*

 

Turkish investigators evaluated the effect of  resveratrol administration on a rabbit model of unhealthy joints. The researches demonstrated a reduction in cartilage injury scores and loss of matrix proteoglycans in the treatment group. (Elmali, N.; Esenkaya, I.; Harma, A.; Ertem, K.; Turkoz, Y.; Mizrak, B. Effect of resveratrol in experimental osteoarthritis in rabbits. Inflamm. Res. 2005, 54, 158–162)

 

Chinese researchers injected resveratrol into the unhealthy knees of mice. The investigators showed that resveratrol was associated with a more balanced inflammatory response and healthier cartilage. (Li et al. JOURNAL OF ORTHOPAEDIC RESEARCH JULY 2015)

2.  Supports Muscle Health*

 

American researchers demonstrated that resveratrol had a protective effect against oxidative stress in the calf muscle of rats. (Jackson JR, Ryan MJ, Hao Y, Alway SE. Mediation of endogenous antioxidant enzymes and apoptotic signaling by resveratrol following muscle disuse in the gastrocnemius muscles of young and old Rats. Am J Physiol Regul Integr Comp Physiol. 2010;299:R1572–R1581.)

3.  Supports Tendon Health*

 

British researchers demonstrated that resveratrol promoted healthy inflammation and counter balanced unhealthy inflammation in human tendon cells. (Busch F, Mobasheri A, Shayan P, Stahlmann R, Shakibaei M. Sirt-1 is required for the inhibition of apoptosis and in ammatory responses in human tenocytes. J Biol Chem 2012;287:25770-81)

4. Boosts Bone Health*

Researchers in Denmark examined the effects of resveratrol on men with metabolic syndrome. The authors found that resveratrol administration was associated with increased spine bone density. The authors concluded that resveratrol positively affects bone by stimulating bone formation and/or mineralization.(Ornstrup MJ et al. Resveratrol increases bone mineral density and bone alkaline phosphatase in obese men: a randomized placebo-controlled trial. J Clin Endocrinol Metab. 2014 Dec;99(12):4720-9.)

Rich Sources

 

 

 

Precautions

While generally well-tolerated, potential side effects of resveratrol include nausea, vomiting, diarrhea, and abdominal pain. High intake may increase risk of bleeding when taken with blood thinners.

More than 1000mg/day of resveratrol has been associated with mild side effects. 

Any consideration of supplementation should be discussed with a qualified health professional.

*These statements have not been evaluated by the Food and Drug Administration. These statements are not intended to diagnose, treat, cure or prevent any disease.

 

References

  1. (2017). Grapes. The World’s Healthiest Foods. Retrieved from http://www.whfoods.com/genpage.php?tname=foodspice&dbid=40
  2. (2017). Resveratrol. Micronutrient Information Center. Retrieved from http://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/resveratrol
  3. Burns, J., Yokota, T., Ashihara, H., Lean, M. E., & Crozier, A. (2002). Plant foods and herbal sources of resveratrol. J Agric Food Chem, 50(11), 3337-40.
  4. Csaki, C., Keshishzadeh, N., Fischer, K., & Shakibaei, M. (2008). Regulation of inflammation signalling by resveratrol in human chondrocytes in vitro. Biochemical Pharmacology, 75, 677–687.
  5. Elmali, N., Esenkaya, I., Harma, A., Ertem, K., Turkoz, Y., & Mizrak, B. (2005). Effect of resveratrol in experimental osteoarthritis in rabbits. Inflammation Research, 54, 158–162. doi:10.1007/s00011-004-1341-6
  6. Kim, H. J., Braun, H. J., & Dragoo, J. L. (2014). The effect of resveratrol on normal and osteoarthritic chondrocyte metabolism. Bone Joint Res, 3(3), 51–59. doi:10.1302/2046-3758.33.2000226
  7. Li, W., Cai, L., Zhang, Y., Cui, L., & Shen, G. (2015). Intra-articular resveratrol injection prevents osteoarthritis progression in a mouse model by activating SIRT1 and thereby silencing HIF-2α. Journal of Orthopaedic Research, 33(7), 1061-70. doi: 10.1002/jor.22859
  8. Mobasheri, A., Henrotin, Y., Biesalski, H., & Shakibaei, M. (2012). Scientific evidence and rationale for the development of curcumin and resveratrol as nutraceutricals for joint health. International Journal Molecular Sciences, 13, 4202-4232. doi:10.3390/ijms13044202
  9. Wendling, D., Abbas, W., Godfrin-Valnet, M., Guillot, X., Khan, K. A., Cedoz, J., & … Herbein, G. (2013). Resveratrol, a sirtuin 1 activator, increases IL-6 production by peripheral blood mononuclear cells of patients with knee osteoarthritis. Clin Epigenetics, 5(1), 10. doi:10.1186/1868-7083-5-10
  10. Ryan MJ, Jackson JR, Hao Y, et al. Suppression of oxidative stress by resveratrol after isometric contractions in gastrocnemius muscles of aged mice. J Gerontol A Biol Sci Med Sci. 2010;65:815–831.
  11. Ghanim H, Sia CL, Abuaysheh S, et al. An antiin ammatory and reac- tive oxygen species suppressive effects of an extract of Polygonum cuspidatum containing resveratrol. J Clin Endocrinol Metab. 2010;95:E1–E8.
  12. Ungvari Z, Labinskyy N, Mukhopadhyay P, et al. Resveratrol attenu- ates mitochondrial oxidative stress in coronary arterial endothelial cells. Am J Physiol Heart Circ Physiol. 2009;297:H1876–H1881. Zhang H, Zhang J, Ungvari Z, Zhang C. Resveratrol improves endo- thelial function: role of TNF{alpha} and vascular oxidative stress. Arterioscler Thromb Vasc Biol. 2009;29:1164–1171.
  13. Wyke SM, Russell ST, Tisdale MJ. Induction of proteasome expres- sion in skeletal muscle is attenuated by inhibitors of NF-kappaB acti- vation. Br J Cancer. 2004;91:1742–1750.
  14. Candelario-Jalil E, de Oliveira AC, Graf S, et al. Resveratrol potently reduces prostaglandin E2 production and free radical formation in lipopolysaccharide-activated primary rat microglia. J Neuroin amma- tion. 2007;4:25.
  15. LagougeM,ArgmannC,Gerhart-HinesZ,etal.Resveratrolimproves mitochondrial function and protects against metabolic disease by acti- vating SIRT1 and PGC-1[alpha]. Cell. 2006;127:1109–1122.
 

 

 

 

 Lucas J. Bader MD

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