Summary of Limonene
Primary Information, Benefits, Effects, and Important Facts
D-Limonene is a compound known as 'lemon extract' and is found in high levels in lemon juices.
It itself, as well as its related product known as 'perillic acid', are known to be anti-carcinogenic (cancer fighting) and liver healthy. Consumption of D-Limonene in either supplemental form or as freshly squeezed and pulp-containing lemonade has been shown to reduce the formation of some tumor growths and alleviate fat buildup in the liver induced by diet.
Although commercial juices tend to have low levels of D-Limonene, freshly squeezed 'Mediterranean Style' juice with the pulp has high levels of it.
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Things To Know & Note
Limonene is non-stimulatory
Limonene is one of the volatiles in citrus fruit responsible for its aroma
Limonene levels are high in citrus peels, and pulp containing juices have higher amounts of limonene than do pulp-free variants
How to Take Limonene
Recommended dosage, active amounts, other details
30-40 liquid oz. of Mediterranean Style (pulp in) lemonade confers approximately 500mg D-Limonene, which can be seen as an active dose.
Otherwise, many benefits are seen with 1g of D-Limonene daily.
Scientific Research on Limonene
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Limonene has its name derived from 'Lemon', the food source that is most abundant in limonene and among the first sources discovered. It is found in:
Limonene is colourless hydrocarbon compound that smells of oranges. Despite the scent, it is at highest levels in the rinds of lemons, where it acquires its name from.
Limonene is rapidly and almost wholly absorbed in the GI tract after ingestion, and then gets divided to various body tissues after first pass metabolism in the liver where it may be subject to metabolism into carveol metabolites or perillyl metabolites by CYP2C enzymes of which inter-species differences exist.
After a 1.6g dose, between 52-83% of the dose is excreted in 48 hours and no build up of the compound is seen 21 days after cessation. The half-life of D-limonene in humans is estimated to be between 12 and 24 hours.
The primary metabolites of limonene in humans are perillic acid, dihydroperillic acid, and limonene-1,2-diol. These metabolites are glucuronidated by the liver and excreted via the urine.
Serum limonene and metabolite levels are able to be elevated via food consumption. A 30-40 oz. serving of 'Mediterranean Style' lemonade (made with the whole lemons) contains 447-596mg limonene.  The termination half-life of perillic acid is shorter than that of D-limonene (in the range of 0.82-1.84 hours) and spiked serum levels of perillic acid 2.08 to 13.98 μM.
In those with Non-alcoholic Fatty Liver disease (onset by diet), supplementation with D-limonene has been shown (in rats) to reverse the hepatic fatty acid buildup as well as downstream effects caused by the hepatic impairment.</di|authors=Victor Antony Santiago J, Jayachitra J, Shenbagam M, Nalini N|journal=Eur J Nutr]
At this moment in time, no scientific consensus exists on D-limonene's role in adipocytes. Select anecdotes, however, suggest it may induce weight loss in high doses.
It, as well as the metabolite perillic acid, do build up in adipocytes over time, which ensures it can actually get to fat cells. Beyond that, it might exert fat-burning effects via suppression of insulin secretion in response to nutrients at pancreatic cells or perhaps vicariously through possibly being an adenosine A(2A) agonistic ligand.
It seems to exert most carcinogenic effects by prevention of protein prenylation at advanced stages of tumorogenesis, and by increasing levels of glutathione in the earlier stages as a preventative measure. Some Phase 1 enzymes of the liver are also affected positively.
Limonene is a fairly safe compound to supplement, and has a Generally Recognized as Safe (GRAS) listing for being a food additive.
It has no significant toxicity in humans. Past research indicated it may accelerate formation of tumors, however this result was found in rats and has since been shown to be of no significance to human metabolism.
- Sun J. D-Limonene: safety and clinical applications. Altern Med Rev. (2007)
- Perez-Cacho PR, Rouseff RL. Fresh squeezed orange juice odor: a review. Crit Rev Food Sci Nutr. (2008)
- Limem-Ben Amor I, et al. Phytochemistry and biological activities of Phlomis species. J Ethnopharmacol. (2009)
- Acharya A, et al. Chemopreventive properties of indole-3-carbinol, diindolylmethane and other constituents of cardamom against carcinogenesis. Recent Pat Food Nutr Agric. (2010)
- Satomi Y, et al. Production of the monoterpene limonene and modulation of apoptosis-related proteins in embryonic-mouse NIH 3T3 fibroblast cells by introduction of the limonene synthase gene isolated from Japanese catnip (Schizonepeta tenuifolia). Biotechnol Appl Biochem. (2009)
- Hyatt DC, et al. Structure of limonene synthase, a simple model for terpenoid cyclase catalysis. Proc Natl Acad Sci U S A. (2007)
- Crowell PL, et al. Human metabolism of the experimental cancer therapeutic agent d-limonene. Cancer Chemother Pharmacol. (1994)
- Miyazawa M, Shindo M, Shimada T. Metabolism of (+)- and (-)-limonenes to respective carveols and perillyl alcohols by CYP2C9 and CYP2C19 in human liver microsomes. Drug Metab Dispos. (2002)
- Shimada T, Shindo M, Miyazawa M. Species differences in the metabolism of (+)- and (-)-limonenes and their metabolites, carveols and carvones, by cytochrome P450 enzymes in liver microsomes of mice, rats, guinea pigs, rabbits, dogs, monkeys, and humans. Drug Metab Pharmacokinet. (2002)
- Kodama R, et al. Studies on the metabolism of d-limonene (p-mentha-1,8-diene). IV. Isolation and characterization of new metabolites and species differences in metabolism. Xenobiotica. (1976)
- Vigushin DM, et al. Phase I and pharmacokinetic study of D-limonene in patients with advanced cancer. Cancer Research Campaign Phase I/II Clinical Trials Committee. Cancer Chemother Pharmacol. (1998)
- Crowell PL, et al. Identification of metabolites of the antitumor agent d-limonene capable of inhibiting protein isoprenylation and cell growth. Cancer Chemother Pharmacol. (1992)
- Pharmacokinetics of Perillic Acid in Humans after a Single Dose Administration of a Citrus Preparation Rich in d-Limonene Content.
- Assessing Dietary D-Limonene Intake for Epidemiological Studies.
- Dietary d-limonene alleviates insulin resistance and oxidative stress-induced liver injury in high-fat diet and L-NAME-treated rats.
- Miller JA, et al. Adipose tissue accumulation of d-limonene with the consumption of a lemonade preparation rich in d-limonene content. Nutr Cancer. (2010)
- Miller JA, et al. Determination of d-limonene in adipose tissue by gas chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. (2008)
- Metz SA, et al. Modulation of insulin secretion from normal rat islets by inhibitors of the post-translational modifications of GTP-binding proteins. Biochem J. (1993)
- Park HM, et al. Limonene, a natural cyclic terpene, is an agonistic ligand for adenosine A(2A) receptors. Biochem Biophys Res Commun. (2011)
- Crowell PL. Monoterpenes in breast cancer chemoprevention. Breast Cancer Res Treat. (1997)
- Crowell PL. Prevention and therapy of cancer by dietary monoterpenes. J Nutr. (1999)
- Tsuda H, et al. Cancer prevention by natural compounds. Drug Metab Pharmacokinet. (2004)
- Gelb MH, et al. The inhibition of protein prenyltransferases by oxygenated metabolites of limonene and perillyl alcohol. Cancer Lett. (1995)
- Effects of anticarcinogenic monoterpenes on phase II hepatic metabolizing enzymes.
- Effects of monoterpenoids on in vivo DMBA-DNA adduct formation and on phase I hepatic metabolizing enzymes.
- Flamm WG, Lehman-McKeeman LD. The human relevance of the renal tumor-inducing potential of d-limonene in male rats: implications for risk assessment. Regul Toxicol Pharmacol. (1991)