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In vitro and animal studies have shown that carrot juice containing bioactive natural products, such as falcarinol (FaOH) and falcarindiol (FaDOH), can affect inflammation. The present study was designed to test whether oral intake of carrot juice containing the bioactive acetylenic oxylipins FaOH and FaDOH affects mediators of acute inflammation or the innate immune response in human blood. Carrot juice (500 mL) was administered orally to healthy volunteers, and blood samples were drawn before and 1 h after juice intake. Next, the blood samples were split in two, and one sample was stimulated ex vivo with lipopolysaccharide (LPS) and incubated at 37 °C for 24 h. The concentrations of 44 inflammatory cytokines and chemokines were examined using multiplex electrochemiluminescence analysis. In blood samples not stimulated with LPS, a significant increase in IL-15 was measured 1 h after carrot juice intake. Cytokines like IFN-ɣ, IL-12/IL-23(p40), IL-23, IL-17A, IL-17B, IL-17D, and IL-22 were significantly increased in LPS-stimulated blood samples after carrot juice intake. The upregulation of the immunostimulating cytokines belonging to the IL-23/IL-17 Th17 axis suggests that carrot juice intake could benefit diseases where inflammation plays a role, like in the early stages of diabetes or cancers. [ABSTRACT FROM AUTHOR]

A prospectively followed Danish cohort of 55,756 citizens with an observation time upwards of 25 years was investigated for association between eating raw carrots on a regular basis and developing various adenocarcinoma-dominant cancers and leukemia. Mean age at inclusion was 56.2 years (SD 4.4 years), and 52% were females. A dose-dependent reduction in incidence was seen for cancer of the lung (HR 0.76, CI95% 0.66; 0.87) and pancreas (HR 0.79, CI95% 0.61; 1.03), as well as leukemia (HR 0.91, CI95% 0.68; 1.21). Only for lung cancer was the association significant. In the case of pancreatic cancer, a possible type 1 error was present due to a low number of cancers. In cases of breast and prostate cancer, no association and no dose response were demonstrated. The association seen for lung and pancreatic cancer parallels that earlier demonstrated for large bowel cancer and indicates a cancer-protective effect from daily intake of raw carrots not limited to gastrointestinal adenocarcinomas. Processed carrots exhibited no effect. The preventive effect could be due to the polyacetylenic compounds falcarinol and falcarindiol in carrots, whereas carotene may not have an effect. The polyacetylenes are inactivated by heating, supporting our findings that only raw carrot intake has an effect. Indirect evidence for the cancer preventive effect of carrots in humans has reached a level where a prospective human trial is now timely. [ABSTRACT FROM AUTHOR]

Falcarindiol (FaDOH) is a cytotoxic and anti-inflammatory polyacetylenic oxylipin found in food plants of the carrot family (Apiaceae). FaDOH has been shown to activate PPARγ and to increase the expression of the cholesterol transporter ABCA1 in cells, both of which play an important role in lipid metabolism. Thus, a common mechanism of action of the anticancer and antidiabetic properties of FaDOH may be due to a possible effect on lipid metabolism. In this study, the effect of sub-toxic concentration (5 μM) of FaDOH inside human mesenchymal stem cells (hMSCs) was studied using white light microscopy and Raman imaging. Our results show that FaDOH increases lipid content in the hMSCs cells as well as the number of lipid droplets (LDs) and that this can be explained by increased expression of PPARγ2 as shown in human colon adenocarcinoma cells. Activation of PPARγ can lead to increased expression of ABCA1. We demonstrate that ABCA1 is upregulated in colorectal neoplastic rat tissue, which indicates a possible role of this transporter in the redistribution of lipids and increased formation of LDs in cancer cells that may lead to endoplasmic reticulum stress and cancer cell death. [ABSTRACT FROM AUTHOR]

• A LC-MS/MS method for the quantification of falcarinol in human blood has been developed. • High sensitivity (LOQ 0.2 ng/mL) and low imprecision (6.9–14.0%) was achieved. • The method was used to study serum levels of falcarinol following intake of a carrot product. • The uptake and clearance of falcarinol occurs rapidly. 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 t ½ 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. [ABSTRACT FROM AUTHOR]

Carrots are consumed worldwide. Several meta-analysis studies on carrot consumption have indicated that carrots play a central role as a protecting vegetable against development of different types of cancers. A cancer-preventive role of carrots is plausible because they are the main dietary source of the bioactive polyacetylenic oxylipins falcarinol (FaOH) and falcarindiol (FaDOH), which have shown anti-proliferative and anti-inflammatory activity in numerous in vitro studies. In addition, purified FaOH and FaDOH have, in recent studies in colorectal cancer (CRC)-primed rats, demonstrated an anti-neoplastic effect in a dose-dependent manner. The mechanisms of action for this effect appears to be due to inhibition of pro-inflammatory and transcription factor biomarkers for inflammation and cancer. However, studies of the CRC-preventive effect of carrots in a large cohort are still missing. We therefore examined the risk of being diagnosed with CRC as predicted by intake of carrots in a Danish population of 57,053 individuals with a long follow-up. Self-reported intake of raw carrots at a baseline of 2–4 carrots or more each week (>32 g/day) was associated with a 17% decrease in risk of CRC with a mean follow-up of >18 years, compared to individuals with no intake of raw carrots even after extensive model adjustments (HR 0.83 CI 95% 0.71; 0.98). An intake below 2–4 carrots each week (<32 g/day) was not significantly associated with reduced risk of CRC (HR 0.93 CI 95% 0.82; 1.06). The results of this prospective cohort study clearly support the results from studies in cancer-primed rats for CRC and hence a CRC-preventive effect of carrots. [ABSTRACT FROM AUTHOR]