gut health


D-Limonene binds to the adenosine A2A receptor so as to increase both intracellular Ca2+ and cyclic AMP. The adenosine A2A receptor. Some highlights of the Wikipedia page of interest to those looking for a natural calming compound. Pressure cooking citrus peel in water does a good job of extracting limonene without the pectin for those that don’t need the extra fiber.

  • Caffeine is a well known antagonist. We know what caffeine can do to GI transit.
  • AdA2A can form heterodimers with other G protein coupled receptors. Wikipedia didn’t mention GPR41 and GPR43
  • AdA2A agonists can suppress immune cells… also acording to Wikipdia authors.

So back to to find out where this receptor is expressed.

A Columbia study compared the terpene profiles of orange oil with different extraction techniques. The use of electric pulses on samples modified their chemical composition, so that the percentage of limonene went from 72% in the sample that was not subjected to electric treatment to lower percentages, even in sample three the percentage of limonene was <50%. Only three compounds (limonene, linalool and caryophyllene) were found to be common in all samples. [2]

An Italian study examined the use of a patented food supplement of limonene absorbed to fiber left over from cocoa processing. [3] Oral limonene, 200mg/kg, peaked in the blood by 30 minutes and was gone by 120 minutes. The limonene absorted to the fiber was found to be not absorbed at all. [3]


  1. Park HM, Lee JH, Yaoyao J, Jun HJ, Lee SJ. Limonene, a natural cyclic terpene, is an antagonistic ligand for adenosine A(2A) receptors. Biochem Biophys Res Commun. 2011 Jan 7;404(1):345-8.
  2. Anaya-Gil J, Cabarcas-Caro A, Leyva-Ricardo M, Parra-Garrido J, Gaitan-Ibarra R, Vivas-Reyes R. Artificial modification of the chemical composition of orange oil (Citrus sinensis L.) and its effect on larvicidal activity. Saudi J Biol Sci. 2021 Mar;28(3):1913-1918.PMC free article
  3. Valerii MC, Turroni S, Ferreri C, Zaro M, Sansone A, Dalpiaz A, Botti G, Ferraro L, Spigarelli R, Bellocchio I, D’Amico F, Spisni E. Effect of a Fiber D-Limonene-Enriched Food Supplement on Intestinal Microbiota and Metabolic Parameters of Mice on a High-Fat Diet. Pharmaceutics. 2021 Oct 21;13(11):1753 PMC free article

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