Limonene, a key active ingredient found in the peels of citrus fruits, has strong antioxidant, anti-inflammatory and anti-cancer properties and many health benefits. Limonene may have the potential to reduce the risk of skin squamous cell carcinoma as well as stabilize disease in colorectal cancer patients and may also have anti-cancer effects in breast cancer patients. In vitro studies also suggest its potential to synergize with Berberine and Docetaxel to inhibit Gastric Cancer and Prostate Cancer, respectively. However, more clinical studies are needed to confirm whether these limonene based combinations are safe and have the same benefits in humans. Also, avoid taking limonene, if you have an allergy to citrus fruit peels.
What is Limonene?
Limonene or D-Limonene is a key ingredient found in the oil extracted from the peels of citrus fruits such as orange, lemon, mandarin, lime and grapefruit. It is one of the most common terpenes (the aromatic compounds found in plants) in nature and is often known as “fragrance” terpene. It is hence a very popular ingredient in cleaning products, cosmetics, and other personal hygiene products. Limonene is also used as a flavoring agent and is found in fruit juices, soft drinks, baked goods, icecreams, and pudding.
D-limonene exhibits strong anti-inflammatory, antioxidant and anticancer properties. It is also considered to be a chemical with fairly low toxicity. It is available as dietary supplements in capsule and liquid form.
General Health Benefits of Limonene
Following are some of the purported uses and general health benefits of Limonene, owing to their anti-inflammatory and antioxidant properties.
- Dissolve cholesterol-containing gallstones.
- Relieve heartburn due to its gastric acid neutralizing effect.
- Reduce obesity
- Manage acute bronchitis.
D-Limonene is usually considered safe for humans with little risk of side effects. However, in some people D-Limonene can cause certain side effects like stomach upset and reflux. Hence, consult your healthcare practitioner before taking D-limonene supplements to avoid any adverse effects/side-effects, especially if you have a medical condition and are undergoing any treatment, are pregnant or breastfeeding. Also ensure that you do not have an allergy to citrus peel or limonene before consuming its supplements.
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Use of Limonene in Cancer
Following are some of the clinical and observational studies associated with the use of Limonene in Cancer.
Impact of Limonene in Women with Early-Stage Breast Cancer
In a clinical trial done by the researchers from the The University of Arizona Cancer Center, 43 women with newly diagnosed operable breast cancer who were scheduled for surgery were given 2 grams of limonene daily for two to six weeks before surgery. The study found that limonene distributed extensively to human breast tissue and its intervention resulted in a 22% reduction in cyclin D1 expression that may lead to cell-cycle arrest and reduced cancer cell proliferation. (Jessica A Miller et al, Cancer Prev Res, 2013)
Impact of Limonene in Patients with Advanced Cancer
In a phase I study conducted by Charing Cross Hospital, London to assess the toxicity, the maximum tolerated dose and pharmacokinetics of Limonene, a group of 32 patients with refractory solid tumors were given 99 courses of 0.5 to 12 g/m2 of oral D-limonene per day in 21-day cycles and 10 breast cancer patients were given 15 cycles of D-limonene at 8 g/m2 per day. The study was followed by a limited phase II evaluation in breast cancer. (D M Vigushin et al, Cancer Chemother Pharmacol., 1998)
The study found that its maximum tolerated dose was 8 g/m2 per day. The results showed a partial response maintained for 11 months in one breast cancer patient who took 8 g/m2 Limonene per day and prolonged stable disease in 3 patients with colorectal cancer.
Impact of Use of Citrus Peel rich in Limonene on the Risk of Squamous Cell Carcinoma of the Skin
In a case-control study done by the researchers from the University of Arizona, they evaluated the association between intake of citrus peels, the principal sources of D-Limonene and the risk of squamous cell carcinoma of the skin. The study did not find any association between the overall consumption of citrus fruits or citrus juices and skin squamous cell carcinoma. Strikingly, those who consumed citrus peels showed a 34% reduced risk of skin squamous cell carcinoma, compared to those who only consumed citrus fruits or their juices. The study also found that the extent of reduction in the risk of skin cancer further increased with higher intake of citrus peels. (I A Hakim et al, Nutr Cancer., 2000)
Other Key Findings in In vitro Studies
Limonene may Improve the Efficacy of Docetaxel in Prostate Cancer
An in vitro study done by the researchers from the Northeastern Ohio Universities Colleges of Medicine and Pharmacy in the United States found that D-Limonene enhanced the antitumor effect of the drug Docetaxel against prostate cancer cells without being toxic to normal prostate epithelial cells. (Thangaiyan Rabi and Anupam Bishayee, J Carcinog., 2009)
Limonene may synergize with Berberine to inhibit Gastric Cancer
Another in vitro study done by the researchers from the Shandong University of Technology, China found that the combination of berberine and d-limonene exerted synergistic anti-cancer effects on gastric cancer cells. (Xiu-Zhen Zhang et al, J Med Food., 2014)
Results from different clinical and observational studies suggest that limonene may have the potential to reduce the risk of skin squamous cell carcinoma, stabilize disease in colorectal cancer patients and have anti-cancer effects in breast cancer patients. Few in vitro studies also suggest its ability to synergize with Berberine and the drug Docetaxel to inhibit Gastric Cancer and Prostate Cancer, respectively. However, more studies are needed to confirm whether these combinations with limonene are safe and effective in humans and also to evaluate its side effects. People who are allergic to citrus fruit peels may also have limonene allergy. Hence, avoid limonene supplements if you have an allergy to citrus fruit peels.
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