Bioaccessibility of Folic Acid and (6S)-5-Methyltetrahydrofolate Decreases after the Addition of Folate-Binding Protein to Yogurt as Studied in a Dynamic in Vitro Gastrointestinal Model

Milk products are only moderate sources of folate. Nevertheless, they are of interest due to their content of folate-binding proteins (FBP), which in some studies have been reported to increase folate bioavailability. The effect of FBP on folate bioavailability has been widely discussed. The aim of this study was to investigate the bioaccessibility of folic acid and (6S)-5-methyltetrahydrofolate (5-CH3-H4folate) from fortified yogurt using a dynamic in vitro gastrointestinal model (TIM). In addition, the effect of FBP on folate bioaccessibility and the stability of FBP added to yogurt during gastrointestinal passage were investigated. Folate bioaccessibility was 82% from yogurt fortified with folic acid and 5-CH 3-H4folate. The addition of FBP to yogurt decreased (P < 0.05) folate bioaccessibility. The lowering effect of FBP was more pronounced in yogurt fortified with folic acid (34% folate bioaccessibility) than from yogurt fortified with 5-CH3-H4folate (57% folate bioaccessibility). After gastrointestinal passage, 17% of the FBP in yogurt fortified with 5-CH3-H4folate and 34% of the FBP in yogurt fortified with folic acid were recovered. No difference in folate bioaccessibility was found between folate-fortified yogurt and folate-fortified pasteurized milk (P = 0.10), whereas the lowering effect of FBP was (P < 0.05) greater in yogurt compared with pasteurized milk. In conclusion, based on the high bioaccessibility of folic acid and 5-CH3-H 4folate, yogurt without active FBP can be considered to be an appropriate food matrix for folate fortification

The Binding of Folic acid and 5-methyltetrahydrofolate to Folate-Binding Proteins during Gastric Passage Differs in a dynamic in vitro gastrointestinal model

Despite its low natural folate concentration, milk is responsible for 10-15% of the daily folate intake in countries with a high dairy consumption. Milk products can be considered as a potential matrix for folate fortification, e.g., with synthetic folic acid, to enhance the daily intake of folate. In untreated milk, the natural folate, 5-methyltetrahydrofolate (5-CH3-H(4)folate), is bound to folate-binding proteins (FBP). In this study, the extent of binding to FBP for folic acid and 5-CH3-H(4)folate was investigated in a dynamic in vitro model simulating human gastric passage. Protein binding of folic acid and 5-CH3-H(4)folate was characterized using gel-exclusion chromatography. Before gastric passage, folic acid and 5-CH3-H(4)folate were bound mainly to FBP (76-79%), whereas 7% was free. Folic acid remained bound to FBP to a similar extent after gastric passage. For 5-CH3-H(4)folate, the FBP-bound fraction gradually decreased from 79 to 5% and the free fraction increased from 7 to 93%. Although folic acid enters the proximal part of the intestine bound to FBP, 5-CH3-H(4)folate appears to be present mainly as free folate in the duodenal lumen. The stability of FBP was similar in both folate/FBP mixtures, i.e., 70% of the initial FBP content was retained after gastric passage. This study indicated that FBP are partly stable during gastric passage but have different binding characteristics for folic acid and 5-CH3-H(4)folate in the duodenal lumen. This could result in different bioavailability from folic acid- and 5-CH3-H(4)folate-fortified milk products

Folic acid and 5-methyltetrahydrofolate in fortified milk are bioaccessible as determined in a dynamic in vitro gastrointestinal model

Dairy products are a potential matrix for folate fortification to enhance folate consumption in the Western world. Milk folate-binding proteins (FBP) are especially interesting because they seem to be involved in folate bioavailability. In this study, folate bioaccessibility was investigated using a dynamic computer-controlled gastrointestinal model [TNO gastrointestinal model (TIM)]. We used both ultrahigh temperature (UHT)-processed milk and pasteurized milk, differing in endogenous FBP concentrations and fortified with folic acid or 5-methyltetrahydrofolate (5-CH3-H(4)folate). To study FBP stability during gastrointestinal passage and the effect of additional FBP on folate bioaccessibility, FBP-fortified UHT and pasteurized milk products were also tested. Folate bioaccessibility and FBP stability were measured by taking samples along the compartments of the gastrointestinal model and measuring their folate and FBP concentrations. Folate bioaccessibility from folic acid-fortified milk products without additional FBP was 58-61%. This was lower (P <0.05) than that of the 5-CH3-H(4)folate-fortified milk products (71%). Addition of FBP reduced (P <0.05) folate bioaccessibility from folic acid-fortified milk (44-51%) but not from 5-CH3-H(4)folate-fortified milk products (72%). The residual FBP levels in the folic acid- and 5-CH3-H(4)folate-fortified milk products after gastrointestinal passage were 13-16% and 0-1%, respectively, of the starting amounts subjected to TIM. In conclusion, milk seems to be a suitable carrier for folate, because both folic acid and 5-CH3-H(4)folate are easily released from the matrix and available for absorption. However, our results suggest that folic acid remains partly bound to FBP during passage through the small intestine, which reduces the bioaccessibility of folic acid from milk in this model

Folic acid and 5-methyltetrahydrofolate in fortified milk are bioaccessible as determined in a dynamic in vitro gastrointestinal model

Dairy products are a potential matrix for folate fortification to enhance folate consumption in the Western world. Milk folate-binding proteins (FBP) are especially interesting because they seem to be involved in folate bioavailability. In this study, folate bioaccessibility was investigated using a dynamic computer-controlled gastrointestinal model [TNO gastrointestinal model (TIM)]. We used both ultrahigh temperature (UHT)-processed milk and pasteurized milk, differing in endogenous FBP concentrations and fortified with folic acid or 5-methyltetrahydrofolate (5-CH3-H(4)folate). To study FBP stability during gastrointestinal passage and the effect of additional FBP on folate bioaccessibility, FBP-fortified UHT and pasteurized milk products were also tested. Folate bioaccessibility and FBP stability were measured by taking samples along the compartments of the gastrointestinal model and measuring their folate and FBP concentrations. Folate bioaccessibility from folic acid-fortified milk products without additional FBP was 58-61%. This was lower (P <0.05) than that of the 5-CH3-H(4)folate-fortified milk products (71%). Addition of FBP reduced (P <0.05) folate bioaccessibility from folic acid-fortified milk (44-51%) but not from 5-CH3-H(4)folate-fortified milk products (72%). The residual FBP levels in the folic acid- and 5-CH3-H(4)folate-fortified milk products after gastrointestinal passage were 13-16% and 0-1%, respectively, of the starting amounts subjected to TIM. In conclusion, milk seems to be a suitable carrier for folate, because both folic acid and 5-CH3-H(4)folate are easily released from the matrix and available for absorption. However, our results suggest that folic acid remains partly bound to FBP during passage through the small intestine, which reduces the bioaccessibility of folic acid from milk in this model

Effects of milk-based phospholipids on cognitive performance and subjective responses to psychosocial stress: a randomized, double-blind, placebo-controlled trial in high-perfectionist men

OBJECTIVES: The aim of this study was to examine the stress-buffering potential of phospholipid (PL) intake on cognitive performance and neuroendocrine and psychological responses under conditions of psychosocial stress in a high-stress vulnerable (perfectionist) sample. METHODS: Fifty-four high-perfectionist men consumed a 6-wk daily intake of a bovine milk-derived PL (2.7 g/d) or placebo drink in a randomized, double-blind, placebo-controlled, parallel groups design. Working memory, executive control function, and acute physiological/subjective responses to an acute psychosocial stressor were examined before and after the 6-wk PL or placebo intake. RESULTS: PL intake improved post-stress reaction time performance on an attention-switching task (P = 0.01). No significant attenuation of the salivary cortisol stress response was shown. PL intake significantly increased mid-stress induction energetic arousal (P = 0.03). A non-significant reduction in anticipatory subjective stress was reported after PL intake (P = 0.06). Systolic and diastolic blood pressures (P<0.04 and P = 0.01, respectively) were significantly augmented in the PL condition. CONCLUSIONS: Dietary intake of bovine milk PLs conferred cognitive performance benefit under conditions of psychosocial stress but failed to moderate cortisol response. Moderation of subjective response to stress exposure may have underpinned this performance protection

Effects of milk-based phospholipids on cognitive performance and subjective responses to psychosocial stress: A randomized, double-blind, placebo-controlled trial in high-perfectionist men

Objective: The stress buffering potential of phospholipid (PL) intake on cognitive performance and neuroendocrine and psychological responses under conditions of psychosocial stress were examined in a high stress vulnerable (perfectionist) sample. Methods: Fifty four high perfectionist males consumed a six week daily intake of a bovine milk-derived PL (2.7g/day) or placebo drink in a randomised, double-blind, placebo controlled, parallel groups design. Working memory, executive control function and acute physiological/subjective responses to an acute psychosocial stressor were examined before and after the six weeks PL or placebo intake. Results: PL intake improved post-stress RT performance on an attention switching task (p = .01). No significant attenuation of the salivary cortisol stress response was shown. PL intake significantly increased mid-stress induction energetic arousal (p = .03). A non-significant reduction in anticipatory subjective stress was reported after PL intake (p = .06). Systolic (p < .04) and diastolic blood (p = .01) pressures were significantly augmented in the PL condition. Conclusions: Dietary intake of bovine milk phospholipids conferred cognitive performance benefits under conditions of psychosocial stress, but failed to moderate cortisol response. Moderation of subjective response to stress exposure may have underpinned this performance protection

Stress responses to repeated exposure to a combined physical and social evaluative laboratory stressor in young healthy males

Repeated exposure to homotypic laboratory psychosocial stressors typically instigates rapid habituation in hypothalamic–pituitary–adrenal (HPA) axis-mediated stress responses in humans. However, emerging evidence suggests the combination of physical stress and social evaluative threat may be sufficient to attenuate this response habituation. Neuroendocrine, cardiovascular and subjective stress responses following repeated exposure to a combined physical and social evaluative stress protocol were assessed to examine the habituation response dynamic in this context. The speech task of the Trier social stress test (TSST; Kirschbaum et al., 1993) and the socially evaluated cold pressor task (SECPT; Schwabe et al., 2008) were administered in a combined stressor protocol. Salivary cortisol, cardiovascular and subjective stress responses to a non-stress control and repeat stressor exposure separated by six weeks were examined in males (N = 24) in a crossover manner. Stressor exposure resulted in significant elevations in all stress parameters. In contrast to the commonly reported habituation in cortisol response, a comparable post-stress response was demonstrated. Cortisol, heart rate and subjective stress responses were also characterised by a heightened response in anticipation to repeated stress exposure. Blood pressure responses were comparatively uniform across repeated exposures. Findings suggest a combined physical and social evaluative stressor is a potentially useful method for study designs that require repeated presentation of a homotypic stressor