While assessment of folate requirements has been based only on dietary intakes, folate produced by the colonic microflora can exceed amounts consumed in food. Bacterially synthesized folate is absorbed across the rat and piglet colon. In vitro studies suggest, but direct evidence is lacking that folate is absorbed across the intact human colon. If indeed folate is absorbed, the amount synthesized may be susceptible to manipulation by fibre and prebiotics intake. We therefore performed two studies to investigate folate absorption across the colon. To confirm absorption across the intact human colon, in our first study, 684 nmol (320 µg) 13C5-glutamyl-[6S]-5-formyltetrahydrofolate was infused into the cecum of six adults and blood samples were collected. Tandem mass spectrometry confirmed folate absorption across the colon by appearance in plasma of 13C5-[6S]-5-methyltetrahydrofolate, at a rate of 0.6±0.2 nmol/h versus 7±1.2 nmol/h after intravenous injection of 172 nmol 13C5-5-formyltetrahydrofolate. Since bifidobacteria are potent folate producers, in our second study we evaluated the influence of bifidogenic oligosaccharides on colonic folate production and host folate status, using a piglet animal model. Piglets (n=12) were randomly assigned a milk-based formula with 5g/L inulin + 5g/L galactooligosaccharides, or 5g/L maltodextrin (control). After 28 days, the weights of colon contents (178 %) and colon tissue (37.9 %) of piglets fed oligosaccharides were greater than controls (P=0.0003, P=0.0044, respectively). The bacterial load and folate contents in the colons of piglets fed oligosaccharides were greater than controls (P=0.0022, P=0.0218, respectively). Body weights, blood folate status and liver and kidney folate concentrations did not differ. In conclusion, folate is absorbed across the human colon. Supplementation of the piglet diet with 5g/L inulin and 5g/L galactooligosaccharides increased the amounts of microbial folate, and the weights of colon tissue and contents, but folate concentrations in colon contents, blood and organs were not affected.

The role of variation in the TAS2R50 bitter taste receptor gene is unknown, but may influence taste perception and dietary habits. Individuals (n=1171) aged 20 to 29, from the Toronto Nutrigenomics and Health Study, completed a food preference checklist and a semi-quantitative food frequency questionnaire to assess their preference and intake of potentially bitter foods and beverages. DNA was isolated from blood and genotyped for 3 polymorphisms in the TAS2R50 gene (rs2900554 A>C; rs10772397 A>G; rs1376251 A>G). Taste intensity was examined using taste strips infused with 3µg of naringin. The rs2900554 SNP was associated with naringin taste intensity, grapefruit preference and grapefruit intake in females. Homozygotes for the C allele reported the highest frequency of experiencing a high naringin taste intensity, disliking grapefruit and not consuming grapefruit. The rs10772397 and rs1376251 SNPs were associated with disliking grapefruit. These results suggest that naringin may be a ligand for the T2R50 receptor.

Red raspberries, as an excellent source of dietary antioxidants, were investigated for their effect on oxidative stress in healthy adults. Study 1 measured effects of chronic exposure in a parallel, multi-dose intervention. Subjects consumed one-cup red raspberries (1cR) daily for two-weeks, then were randomized to consume 1cR, 2cR or 4cR for additional two-weeks (n=8, by group). There was a reduction in TBARS, indicating a decrease in lipid peroxidation, after two-weeks of intervention in the 1cR group, but effects were not significant at week 4, or for other treatment groups. Study 2 measured effects of acute exposure using a cross-over design. Subjects (n=8) consumed single treatments of 1cR, 2cR, 4cR, bread and bread plus vitamin C. Post-prandial oxidative stress responses were complex and appeared related to calorie and antioxidant load. Overall there was no clear relationship between red raspberry consumption and protection against oxidative stress.

Folate intake in North America has drastically increased over the past decade due to folic acid fortification and widespread supplemental use. The role of folate in breast cancer is highly controversial and the effects of folic acid supplementation on breast cancer patients are currently unknown. An animal study was performed to determine the effects of folic acid supplementation on the progression of the mammary tumors in the DMBA-carcinogen model. Folic acid supplementation was associated with more rapid sentinel tumor progression and with higher sentinel tumor weight, volume, and area, although no clear dose-responsive relationship was observed. Folic acid supplementation was associated with an increased expression of proapoptotic protein PARP and decreased expression of proliferation protein PCNA. These data suggest that folic acid supplementation may promote the progression of established mammary tumors. Whether or not folic acid supplementation may adversely affect the outcome of patients with breast cancer warrants further studies.

In response to evidence of inadequate fibre and magnesium intakes across the Canadian population, the most recent edition of Canada’s Food Guide included a recommendation for increased whole grain consumption. However, whole grain labelling on food packaging remains voluntary and unregulated. The aim of this research was to examine the nature of nutrition guidance provided by whole grain labelling in the Canadian marketplace through a survey of front-of-package nutrition-related marketing in three supermarkets and a detailed examination of nutrient content, ingredients, and price of breads. Whole grain promotion occurred on relatively few products, predominantly among processed foods, and it frequently appeared in conjunction with references to other nutritional characteristics. The whole grain labelling observed was not misleading with respect to highlighting products with whole grain ingredients and higher levels of fibre and magnesium content; however, products with whole grain labelling were less likely to be lower in price.

Non-alcoholic fatty liver disease (NAFLD) includes simple hepatic steatosis (SS) and non-alcoholic steatohepatitis (NASH). NAFLD is tightly linked to obesity and is thought to be secondary to various noxious signals, some of which may originate from the intestinal microbiota (IM). Despite a growing body of evidence supporting a link between obesity and altered IM, there are no studies assessing the IM of patients with NAFLD. In this cross-sectional study we aimed at comparing fecal levels of total bacteria, Bacteroidetes, C. coccoides, C. leptum, Bifidobacteria, E. coli, and Archaea between healthy controls (HC) and patients with SS or NASH. We found higher C. coccoides levels in NASH compared to SS and lower percentage Bacteroidetes in NASH compared to SS and HC. Controlling for body mass index and fat intake we found an association between presence of NASH and percentage Bacteroidetes. The latter inversely correlated with insulin resistance.

Folate blood levels in North America have dramatically increased over the past decade owing to folic acid (FA) fortification and widespread supplement use. Furthermore, over 50% of newly diagnosed colorectal cancer (CRC) patients use vitamin supplements containing FA while receiving chemotherapy whose mechanisms of action are based on interruption of folate metabolism. This study therefore investigated whether FA supplementation can affect chemosensitivity of human colon cancer cells to 5FU, the cornerstone of CRC treatment, using a xenograft model. FA supplementation was associated with a non-dose dependent decrease in chemosensitivity, where mice receiving 8 mg FA did not respond to 5FU and had greater tumor growth with treatment, compared to 2 (control) or 25 mg FA. Results of this study pose concern given the drastically increased intake of FA, particularly among recently diagnosed CRC patients, and from mandatory fortification. Further studies are warranted to confirm our findings and to elucidate underlying mechanisms.

In order to examine the effects of industry processed pulse powder (navy bean, lentil and chickpea) on postprandial glycaemic response (BG) and subjective appetite (App) before and after a subsequent meal, three randomized, within-subject experiments on healthy young men were conducted. In experiment 1, all navy bean treatments reduced BG at 30 min and navy bean powder suppressed pre-meal App compared to whole wheat flour. In experiment 2, all lentil treatments reduced pre-meal BG compared to whole wheat flour. However, no App differences were observed. In experiment 3, all chickpea treatments reduced pre-meal BG compared to whole wheat flour. However, no App differences were observed. Therefore, navy bean powder, lentil powder and chickpea powder maintain their low GI and satiating effects, regardless of processing. Pulse powder can be used as a value-added food ingredient to moderate glycaemic response and increase satiety.

Folate is an essential cofactor in one-carbon transfer reactions including nucleotide biosynthesis, thereby playing an important role in DNA replication and repair. In cancer cells, folate depletion interrupts DNA synthesis, thereby causing cancer cell death. This has been the basis for chemotherapy using antifolates and 5-fluorouracil (5FU). We determined the effect of folate deficiency on the sensitivity of colon cancer cells to 5FU in a well established in vitro model of folate deficiency. Folate deficient cells had lower intracellular folate concentrations, had functional evidence of intracellular folate depletion, proliferated less, and had increased chemosensitivity to 5FU with and without Leucovorin. These data suggest that folate deficiency significantly enhances the sensitivity of colon cancer cells to 5FU based chemotherapy via changes in intracellular folate. Dietary or other strategies to deplete intracellular folate concentrations in colon cancer cells to enhance chemosensitivity to 5FU are worthy of further investigation.

All populations risk vitamin D inadequacy. We conducted a randomized double- blind trial of vitamin D3 fortified cheddar cheese to study bioavailability based on serum 25-hydroxyvitamin D [25(OH)D] concentrations, and its effects on mental health scores in older adults. Once a week, 28 subjects received 200 IU or 28000 IU of vitamin D3 per fortified cheese serving. The mean increases in 25(OH)D over 8 weeks were: 4.2±11.4 and 29.4±16.2 for the 200 IU/week and 28,000 IU/ week dose groups, respectively (groups differ, P<0.001). Subjects who consumed 28,000 IU/week cheese improved their Mental Component Summary (MCS) scores, based upon the SF-36v2 questionnaire conducted at baseline and at 8 weeks (P<0.05). There was also a positive correlation between the change in MCS score and the change in 25(OH)D (1 tail; P<0.05). These data demonstrate the suitability of fortified cheddar cheese, and provide evidence of neurocognitive benefits with higher 25(OH)D levels.