Abstract B125: Adipose tissue accumulation of d-limonene with the consumption of a lemonade preparation rich in d-limonene content.

d-Limonene is a bioactive food component commonly found in high concentration in citrus peel. It has demonstrated anti-cancer effects in preclinical studies with the most compelling results in mammary carcinogenesis models. Information on the oral bioavailability and tissue disposition of d-limonene in humans is rather limited for extrapolation of preclinical data to human situations. As a fat-soluble compound, d-limonene is more likely to deposit in fatty tissues such as the breast where we hypothesize that biologic activity may be greatest. We conducted a clinical study to determine the systemic and adipose tissue disposition of d-limonene with the consumption of a lemonade preparation rich in d-limonene content.

Seven healthy adults underwent a one-week washout period during which their diets were void of all citrus. At entry, participants consumed a breakfast that included the freshly prepared lemonade (40 oz containing 0.6 gm d-limonene) in the clinic. Serum and needle fat biopsies of the buttocks were collected 6 hours post-feeding. Participants then consumed 40 oz of freshly prepared lemonade daily for 4 weeks. At completion of the 4-week feeding period, participants repeated the controlled breakfast with high d-limonene lemonade prepared in the clinic followed by repeat serum and fat sampling. Matched pre- and post-intervention fat biopsies (n = 7) and serum samples (n = 6) were analyzed for d-limonene levels using gas chromatography-mass spectrometry.

The d-limonene levels in the initial fat biopsies ranged from non-detectable to 0.79 μM (median = 2.55 μM) concentration. The adipose d-limonene levels increased significantly (p < 0.01) after 4 weeks of intervention with levels ranging from 53.56 to 293 μM (median = 99.68 μM). There was a slight but statistically significant increase (p < 0.05) in serum d-limonene levels after 4 weeks of intervention; initial levels ranged from 0.35 - 0.72 μM (median = 0.46 μM) and post intervention levels ranged from 0.54 - 1.65 μM (median = 1.20 μM). The adipose d-limonene levels were significantly higher than the serum d-limonene levels (p < 0.05).

Oral consumption of high d-limonene lemonade results in d-limonene deposition in adipose tissue in levels much higher than levels in the systemic circulation. Assessing the serum d-limonene levels is not likely to reflect d-limonene exposure in the adipose tissue. In addition, given d-limonene’s anticarcinogenic properties, and because breast tissue is mostly composed of adipose, the data suggests that d-limonene could also accumulate at this site, thus potentially modulating breast cancer risk.

Citation Information: Cancer Prev Res 2008;1(7 Suppl):B125.