Dietary butyrylated high-amylose starch reduces azoxymethane-induced colonic O(6)-methylguanine adducts in rats as measured by immunohistochemistry and high-pressure liquid chromatography.

O(6)-methyl guanine (O(6)MeG) adducts are major toxic, promutagenic, and procarcinogenic adducts involved in colorectal carcinogenesis. Resistant starch and its colonic metabolite butyrate are known to protect against oncogenesis in the colon. In this study, we hypothesized that a dietary intervention that specifically delivers butyrate to the large bowel (notably butyrylated high-amylose maize starch [HAMSB]) would reduce colonic levels of O(6)MeG in rats shortly after exposure to the deoxyribonucleic acid (DNA) alkylating agent azoxymethane (AOM) when compared with a low-amylose maize starch (LAMS). A further objective was to validate an immunohistochemistry (IHC) method for quantifying O(6)MeG against a high-performance liquid chromatography method using fluorescence and diode array detection. Rats were fed either LAMS or HAMSB diets for 4 weeks followed by a single injection of AOM or saline and killed 6 hours later. After AOM exposure, both IHC and high-performance liquid chromatography method using fluorescence and diode array detection measured a substantially increased quantity of DNA adducts in the colon (P<.001). Both techniques demonstrated equally that consumption of HAMSB provided a protective effect by reducing colonic adduct load compared with the LAMS diet (P<.05). In addition, IHC allowed visualization of the O(6)MeG distribution, where adduct load was reduced in the lower third of the crypt compartment in HAMSB-fed rats (P=.036). The apoptotic response to AOM was higher in the HAMSB-fed rats (P=.002). In conclusion, the reduction in O(6)MeG levels and enhancement of the apoptotic response to DNA damage in the colonic epithelium through consumption of HAMSB provide mechanistic insights into how HAMSB protects against colorectal tumorigenesis.

Bioequivalence of n-3 fatty acids from microencapsulated fish oil formulations in human subjects.

Fish oil n-3 fatty acids (FA) have known health benefits. Microencapsulation stabilises and protects fish oil from oxidation, enabling its incorporation into foods. The aim of the present study was to compare the bioavailability of n-3 FA delivered as two microencapsulated fish oil-formulated powders or fish oil gel capsules (FOGC) taken with a flavoured milk in healthy participants. Formulation 1 (F1) composed of a heated mixture of milk protein-sugar as an encapsulant, and formulation 2 (F2) comprised a heated mixture of milk protein-sugar-resistant starch as an encapsulant. Participants consumed 4 g fish oil (approximately 1·0 g EPA and DHA equivalent per dose). Bioavailability was assessed acutely after ingestion of a single dose by measuring total plasma FA composition over a period of 48 h (n 14) using a randomised cross-over design, and over the short term for a period of 4 weeks using an unblinded parallel design (after daily supplementation) by measuring total plasma and erythrocyte FA composition at baseline and at 2 and 4 weeks (n 47). In the acute study, F1 greatly increased (% Δ) plasma EPA and total n-3 FA levels at 2 and 4 h and DHA levels at 4 h compared with FOGC. The time to reach maximal plasma values (T(max)) was shorter for F1 than for FOGC or F2. In the short-term study, increases in plasma and erythrocyte n-3 FA values were similar for all treatments and achieved an omega-3 index in the range of 5·8-6·3 % after 4 weeks. Overall, the results demonstrated human bioequivalence for microencapsulated fish oil powder compared with FOGC.