Effect of Beta- and Alpha-Carotene Intake on Tumour Formation in the Intestines of APCMin/+ Mice

Carotene-rich vegetables like carrots have been consistently associated with lowered cancer risk in observational studies (1) . Beta-carotene, a phytochemical found in fruits and vegetables, is known for its antioxidant properties. In rodent trials, supplementation with carrot (containing both carotenes and polyacetylenes) significantly reduced tumour numbers in the APC Min/+ mouse model (2) . However, human intervention trials with pure beta-carotene showed more adverse effects than benefits (3) . This study aimed to investigate the impact of beta- and alpha-carotene supplementation (without polyacetylenes) on colorectal cancer using the APC Min/+ mouse model, which spontaneously develops intestinal tumours and an enlarged liver (4) . APC Min/+ mice were fed either a daily supplement of 10mg/kg mouse of a polyacetylene-free extract from carrots containing a beta- and alpha-carotene mixture, in a dose corresponding to the beneficial carrot supplementation, or the control diet, with a very low beta-carotene content (providing approx. 0.02mg/kg mouse/day). The 8-week supplementation commenced at 5 weeks of age. Tumour quantification in the small intestines of APC Min/+ mice was performed by histology of the entire small intestine, with one slide per 0.3mm, using the H&E staining method and Imagescope software. Supplementation with carotenes had no significant effect on the total number of tumours (≥0.5 mm), showing no discernible difference between the control (n = 6) (20.5, 95% CI [14.69, 26.31]) and treatment (n = 8) (24.5, [19.21, 29.79]) group (P = 0.237). However, the liver weight, in % of body weight, showed a significant 25% decrease in the treatment group (n = 7) (4.78 95% CI [4.45, 5.15]) compared to controls (6.42, [5.71, 7.13]) (P<0.0003), reaching a level comparable with wildtype mice (4.48, [4.13, 4.83]. These findings confirm the results from the human intervention trials by indicating that beta- and alpha-carotene do not confer any benefit for cancer prevention, while the decrease in liver weight suggests a potential beneficial effect on another aspect of liver health. Additional research is necessary to fully understand these relationships and uncover the underlying mechanisms behind these results. Specifically, beta-and alpha-carotene from carrots do not provide the reduction in tumour numbers in a mouse model of colon cancer found when feeding the corresponding dose of freeze-dried carrot. However, the carotenes significantly attenuate the liver enlargement also seen in this model.