Quantification of the anti-neoplastic polyacetylene falcarinol from carrots in human serum by LC-MS/MS.

Falcarinol is a polyacetylene which is found in carrots and known to have anti-neoplastic properties in rodents. Research in the bioactivity of falcarinol in humans require methods for quantification of falcarinol in human serum. Here we report the development of an LC-MS/MS method and its use to measure serum falcarinol concentrations in humans following intake of a carrot product. Falcarinol was measured by LC-MS/MS using the m/z 268 to m/z 182 mass transition. Six calibrator levels (0.2-20 ng/mL) and 3 control levels (0.4, 2 and 8 ng/mL) were prepared by addition of falcarinol to human serum pools. Linearity of the developed method was good with a mean R2 of 0.9942. Within-day, between-day and total coefficients of variation were 6.9-13.1%, 4.1-5.0% and 8.1-14.0%, respectively. The limits of detection and quantitation were 0.1 and 0.2 ng/mL, respectively, matrix effects 84.2%, recovery 101.4-105.4% and carry-over -0.24-0.07%. Serum falcarinol concentrations were measured in 18 healthy volunteers prior to and at 9 time-points following intake of a carrot product. Falcarinol concentrations peaked at the 1-hour time-point after intake in 15 out of 18 volunteers and declined according to a single exponential decay function with an aggregate t½ of 1.5 h. In conclusion, an LC-MS/MS method for quantification of falcarinol in human serum with acceptable performance was developed and used to measure falcarinol concentrations following intake of a carrot product.

Can coffee or chewing gum decrease transit times in Colon capsule endoscopy? A randomized controlled trial.

BACKGROUND: A high rate of complete colon capsule endoscopy (CCE) investigations is required for a more widespread use of CCE. The objective of this study was to assess if coffee or chewing gum can increase excretion of the colon capsule within battery life time (excretion rate). METHODS: One hundred eighty six screening participants with a positive immunochemical fecal occult blood test were included in this single-centre randomized controlled trial with blinding of the investigators to the randomization. Participants received instant coffee, chewing gum or nothing in addition to the standard bowel preparation. RESULTS: The intention was to include 57 participants in the coffee group, 61 in the chewing gum group and 60 in the control group, on 8 participants data were missing. A total of 165 participants were included in a per protocol analysis. Exclusion was due to not receiving the allocated intervention (8 coffee, 4 chewing gum) and technical failure of the capsule (1 coffee). The excretion rate was 58% in the coffee group (n = 48), 63% in the chewing gum group (n = 57) and 55% in the control group (n = 60, p > 0.2). Transit times were similar in all groups. The excretion rate was low in participants who had transit times over 10 h (14%). A strong correlation was found between adequate cleansing and excretion of the capsule. There were no serious adverse events related to the interventions or CCE investigations. CONCLUSIONS: Chewing gum and coffee did not improve excretion rate in this study. An effect of chewing gum could not be proven, possibly due to sample size. Since chewing gum might improve excretion rates, is cheap and has no known side effects, it needs to be considered in future bowel preparation trials for CCE. TRIAL REGISTRATION: NCT02303756 , registered on December 1st 2014.

Dietary polyacetylenes, falcarinol and falcarindiol, isolated from carrots prevents the formation of neoplastic lesions in the colon of azoxymethane-induced rats.

Falcarinol (FaOH) and falcarindiol (FaDOH) are found in many food plants of the Apiaceae family. Carrots are a major dietary source of these polyacetylenes. Feeding azoxymethane (AOM)-induced rats with carrots and purified FaOH have previously been shown to inhibit neoplastic transformations in the colon. FaOH and FaDOH have also shown to have a synergistic effect in vitro, resulting in a significant increased cytotoxic activity. Based on these findings the antineoplastic effect of FaOH and FaDOH (purity > 99%) was investigated in the AOM-induced rat model. Twenty rats received rat diet containing 7 µg FaOH per g feed and 7 µg FaDOH per g feed and 20 rats were controls receiving only rat diet. Then carcinogenesis was induced in all 40 rats with the carcinogen AOM. All animals received the designated diet for 2 weeks before AOM induction and continued on the designated diet throughout the experiment. Rats were euthanized 18 weeks after the first AOM injection and macroscopic polyp/cancers were measured, harvested and stained for histology. The difference in sizes of aberrant crypt foci (ACF) were analysed in a Wilcoxon rank sum test, in which the median number of small ACF was 218 in controls and 145 in polyacetylene treated rats (P < 0.001). Fifteen control rats and 8 treated rats had macroscopic tumors (P = 0.027). The number of tumors larger than 3 mm were 6 and 1 in control and treated rats, respectively (P = 0.032). In conclusion dietary supplements with FaOH and FaDOH reduced the number of neoplastic lesions as well as the growth rate of the polyps suggesting a preventive effect of FaOH and FaDOH on the development of colorectal cancer.

Inhibitory effects of feeding with carrots or (-)-falcarinol on development of azoxymethane-induced preneoplastic lesions in the rat colon.

The effects of intake of dietary amounts of carrot or corresponding amounts of (-)-(3R)-falcarinol from carrots on development of azoxymethane (AOM)-induced colon preneoplastic lesions were examined in male BDIX rats. Three groups of eight AOM-treated rats were fed the standard rat feed Altromin supplemented with either 10% (w/w) freeze-dried carrots with a natural content of 35 mug falcarinol/g, 10% maize starch to which was added 35 mug falcarinol/g purified from carrots, or 10% maize starch (control). After 18 weeks, the animals were euthanized and the colon was examined for tumors and aberrant crypt foci (ACF), which were classified into four size classes. Although the number of small ACF was unaffected by the feeding treatments, the numbers of lesions as a function of increasing size class decreased significantly in the rats that received one of the two experimental treatments, as compared with the control treatment. This indicates that the dietary treatments with carrot and falcarinol delayed or retarded the development of large ACF and tumors. The present study provides a new perspective on the known epidemiological associations between high intake of carrots and reduced incidence of cancers.