by Robert Tisserand, with thanks to Christine Carson and Linda Halcon for their input.
In the United States, breast cancer is the most common cancer in women, and it is the second most common cause of death from any cancer. According to the National Cancer Institute 12.3% of women will be diagnosed with breast cancer at some point during their lifetime, based on 2010-2012 data. In 2012, there were an estimated 2.9 million women living with breast cancer in the United States. Risk factors, and common ways to avoid them, are elaborated here. Types of breast cancer are listed here.
There has been much research on citrus fruits, citrus oils, and limonene in relation to breast cancer, and recent developments seem to suggest at least a preventive effect. Treatment of any cancer is a significant challenge, and I want to be clear that I am not advocating an alternative breast cancer treatment regime. This is about prevention. That doesn’t mean this regime will be useless in combination with other therapies. It may have some effect, but is not likely to be effective as a stand-alone treatment.
Limonene is the major constituent of citrus fruit oils, and is found in orange, tangerine and grapefruit oils at about 90%, and in lemon and mandarin oils at about 70%. Research in the 80s showed that limonene (or in one case orange oil) could either inhibit the development of breast cancer in female rodents, or could cause regression of existing tumors (6,7,8,9,12,19). In the mid 1990s, 11 patients with advanced breast cancer were included in one clinical trial using high oral doses of limonene. There was regression of disease in only one patient (22). Perillyl alcohol, a metabolite of limonene, was similarly trialed in a small group of patients with advanced breast cancer, also without success (2). However, while the use of oral limonene as a cancer treatment option has stalled, it is now showing great promise in breast cancer prevention and for this purpose, topical application appears to be as effective as oral dosing. [It is also worth noting that two minor constituents of many citrus oils, bergapten and citral, have shown in vitro activity against breast cancer cells (3,4).]
Prevention is difficult to prove, but a scientific team around Jessica Miller at the University of Arizona has been focusing their energies on limonene and breast health for the past 7 years. So far they have published five papers. First, the team established a method to measure limonene in body fat (13), and then they reported that limonene is preferentially absorbed into buttock fat (14). This was found in 7 healthy adults (one male, 6 females) who drank lemonade made from whole lemons every day for four weeks. After the first 6 hours, there was 8 times more limonene in body fat than in the blood; after four weeks, the difference increased to 34 times, showing that limonene accumulates in fatty tissue. So at this point we know that limonene is drawn to fat cells in the body. In fact, as far as we know, it stays there for longer than most other essential oil constituents.
The team then found that either oral or topical administration of orange oil to female mice resulted in preferential absorption of limonene into breast tissue, with similar amounts being present from oral as from topical (15). In the same study, healthy women were recruited to apply orange oil, diluted to 10% or 20% in fractionated coconut oil, to their breasts. This was determined to be both safe and feasible.
Following this, 43 women with newly diagnosed, operable breast cancer were recruited to ingest two grams of limonene daily for 2-6 weeks (the time varied with scheduled surgery). In this clinical trial, limonene again preferentially concentrated in breast tissue (see illustration). In addition, there was a 22% reduction in cyclin D expression. This is interesting, since cyclin D is an important factor in rates of cell growth, and is overexpressed in hyperplasia and intraductal carcinoma of the breast, suggesting this plays a role in the earliest stages of breast cancer development (16).
Cancer prevention with natural compounds is not just about direct action against any cancer cells that may arise, and also involves effects such as immune-enhancing, antimutagenic and antioxidant (21). Interestingly, these indirect cancer protective effects have all been established for limonene (1,5,10,18). In their latest research paper, Jessica Miller and colleagues studied the effect of limonene on hundreds of substances in the body, such as adrenal hormones, amino acids and glucose metabolites. These were blood tests that were conducted during the previously described clinical trial (17). An important conclusion was that limonene counteracts many of the metabolic changes that happen in people with breast cancer, strongly suggesting a preventive effect.
Citrus fruit consumption
The above studies on limonene suggest breast cancer preventive effects, and it is worth noting that there is also epidemiological evidence from the consumption of citrus fruit. Several such reports looked at the relationship between citrus fruit consumption and breast cancer incidence. A meta-analysis of five studies found an overall 10% reduction in breast cancer incidence, associated with “high intake” of citrus fruits. A Japanese report not included in this review concluded that daily citrus consumption was correlated with an 11% reduced incidence of all cancers in both sexes. The effect was even greater (17%) in those who also drank green tea every day (11). An association with citrus fruits does not necessarily mean that the essential oil, or limonene, is solely responsible, in fact this is unlikely as citrus fruits contain many anticancer substances, not all found in the essential oil.
There is growing evidence that citrus fruit, and limonene-rich citrus essential oils could play a role in the prevention of breast cancer. It is not implausible that combination of fresh oranges, green tea and a topical essential oil formulation could be preventive for many people. However, we need to know more about the safety and efficacy of long-term topical use.
- Bacanlı, M., Başaran, A. A., & Başaran, N. (2015). The antioxidant and antigenotoxic properties of citrus phenolics limonene and naringin. Food and Chemical Toxicology, 81, 160–170
- Bailey, H. H., Attia, S., Love, R. R. et al (2008). Phase II trial of daily oral perillyl alcohol (NSC 641066) in treatment-refractory metastatic breast cancer. Cancer Chemotherapy and Pharmacology, 62(1), 149–157
- Chaouki, W., Leger, D. Y., Liagre, B. et al (2009). Citral inhibits cell proliferation and induces apoptosis and cell cycle arrest in MCF-7 cells. Fundamental & Clinical Pharmacology, 23(5), 549–556
- De Amicis, F., Aquila, S., Morelli, C. et al (2015). Bergapten drives autophagy through the up-regulation of PTEN expression in breast cancer cells. Molecular Cancer, 14(1), 130
- Del Toro-Arreola, S., Flores-Torales, E., Torres-Lozano, C. et al (2005). Effect of d-limonene on immune response in BALB/c mice with lymphoma. International Immunopharmacology, 5(5), 829–838
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- Elson, C. E., Maltzman, T. H., Boston, et al (1988). Anti-carcinogenic activity of d-limonene during the initiation and promotion/progression stages of DMBA-induced rat mammary carcinogenesis. Carcinogenesis, 9(2), 331–332
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