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Nootkatone is a sesquiterpene derived ketone from grapefruit, with a structure reminiscent of the lower portion and moieties of many steroids. In fact, nootkatone has been demonstrated to inhibit the negative endocrine effects of tobacco, including restoration of circulating testosterone levels following their inhibition by tobacco smoke inhalation (1). This suggests a protective role of nootkatone in the androgen system against external endocrine toxins, whilst reducing oxidative stress markers (1).


Nootkatone is also an inducer of AMPK, increasing AMP/ATP ratio, and resulting in increased whole-body energy expenditure while decreasing high-fat and high-sugar diet induced weight gain and fat accumulation (2). The compound also augments endurance capacity by up to 21% when used long-term, as a result of enhanced skeletal muscle energy metabolism and glucose transport (2).

Nootkatone also upgregulates PPARγ coactivator-1α (PGC-1α), the master regulator gene controlling mitochondrial biogenesis, and as such mimics some of the beneficial effects of endurance exercise, potentially enhancing many metabolic benefits obtained when exercising (2).

Furthermore, nootkatone protects liver tissue via antioxidant and anti-inflammatory effects (4).

 Key references:

  • Inhibits decrease of testosterone (1)

  • Stimulates fatty acid oxidation and inhibits lipogenesis (2)

  • Liver protective via antioxidant and anti-inflammatory activities (4)


1 - Ali, B. H., Al-Salam, S., Adham, S. A., Al Balushi, K., Za'abi, A., Beegam, S., & Nemmar, A. (2019). Testicular toxicity of water pipe smoke exposure in mice and the effect of treatment with nootkatone thereon. Oxidative medicine and cellular longevity, 2019.

2 - Murase, T., Misawa, K., Haramizu, S., Minegishi, Y., & Hase, T. (2010). Nootkatone, a characteristic constituent of grapefruit, stimulates energy metabolism and prevents diet-induced obesity by activating AMPK. American Journal of Physiology-Endocrinology and Metabolism, 299(2), E266-E275.

3 - Seo, E. J., Lee, D. U., Kwak, J. H., Lee, S. M., Kim, Y. S., & Jung, Y. S. (2011). Antiplatelet effects of Cyperus rotundus and its component (+)-nootkatone. Journal of ethnopharmacology, 135(1), 48-54.

4 - Al Kurdy, A. A. (2016). Study of the Effect of Nootkatone on Liver Fibrosis. Beirut Arab University.

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