Impact of Age, Meal, Diet and Digestive Discomfort on B-Vitamin Bioavailability

Abstract

B-vitamin inadequacy is a major health concern in older adults, yet there remains a poor understanding of B-vitamin requirements specific to the ageing population. The B-vitamins need to be efficiently metabolised to produce biologically active derivatives, the vitamers which exist in several forms and play fundamental roles as co-factors of numerous enzymes regulating cellular metabolic pathways. Preventing or ameliorating the depletion of these vitamins at an early stage from the time of dietary intake may slow or even prevent disease development in old age. However, such approaches first require a detailed understanding of how B-vitamins are digested and metabolised immediately following ingestion under varying conditions related to the dietary environment and ageing. Such insight into the processes involved can be achieved by assessing the availability of B-vitamin biomarkers that appear in circulation immediately following a meal or following recent changes in dietary patterns. Yet, despite increasing concerns for adequacy of these essential B-vitamins in the elderly, there remains a paucity of evidence from intervention studies that demonstrate impact on circulating B-vitamin and vitamer concentrations, relative bioavailability between age groups, between meal compositions or effects in those with gastrointestinal disturbances. Hence, with the hypothesis that differing meal structure and gastrointestinal disturbances may impact B-vitamin status of the elderly, the primary aim of this thesis was to understand how older people absorb or utilise B-vitamins via undertaking clinical trials and performing comprehensive analysis of B-vitamins and vitamer responses. The outcomes detailed in this thesis provides a baseline understanding that will inform on the further research required in order to establish standardized B vitamin requirements in the elderly. Along with B-vitamins, increasing concerns around protein malnutrition are similarly prevalent in the elderly who are encouraged to increase intake of protein-rich foods, which are also key sources for some of the B-vitamins. Therefore, increasing intake of protein-rich foods might be a strategy that allows maintenance of adequate B-vitamin status in ageing. Research literature in this area is limited and thus represented the first aim of this thesis. This study utilised a 10-week diet intervention in a randomised controlled parallel design conducted in 29 healthy older men. The results demonstrated that increasing protein-rich whole food intake improves B-vitamin concentrations, particularly riboflavin, in healthy older men. To improve adequacy, many older adults use supplements expecting health benefits, but evidence of improved health outcomes is limited, and deficiencies remain prevalent. However, studies to date that have examined the acute postprandial response of circulating and urinary B-vitamins following supplement ingestion, particularly in older adults also remain limited and therefore provided the second aim of this thesis. This was accomplished by undertaking an acute open-label trial in which 20 healthy older (65-76 years old, men n=10 and women n=10) and 20 healthy younger (19-30 years old, men n = 10 and women n = 10) ingested a commercially available multivitamin and mineral supplement. The results showed significantly different responses between age groups of several B-vitamin responses such that, thiamine, riboflavin, pantothenic acid and 4-pyridoxic acid (4-PA) were greater whereas, pyridoxine and pyridoxal-5’ phosphate (PLP) were lower in older adults. These results indicated that either absorption, subsequent metabolic conversion or utilisation of these vitamins is altered with increasing age. In particular, the differences in B6-vitamers (pyridoxine, PLP and 4-PA), indicated an alteration in either absorption or subsequent metabolic interconversion of supplemental vitamin B6 in ageing people, with potential implications for its biological function. While supplements are an aid to improve adequacy of B-vitamins, intake from whole food is prioritised as supplements are not designed to replace a healthy meal. However, the impact of meal composition on the postprandial availability of these vitamins has not been studied in older adults, providing the third aim for this thesis. This study involved 15 healthy young and 15 healthy older male and female adults who ingested either an energy dense (ED) or a nutrient dense (ND) breakfast meal with varying composition in a randomised cross-over design. This study showed that postprandial availability of B-vitamins following a single meal may not be compromised in healthy older individuals and highlights the importance of absolute intake, particularly riboflavin, to increase circulating concentrations. Given the importance of milk as a highly bioavailable source of dietary B-vitamins, particularly riboflavin, older adults who frequently report lactose intolerance and suffer gastrointestinal disturbances may be at increased risk of riboflavin depletion. Therefore, a study was conducted with the aim of understanding whether being dairy intolerant impacts upon the postprandial availability of riboflavin and other B-vitamins and if this availability differs with the type of milk ingested. Forty self-reported milk tolerant and intolerant young women classified as either dairy tolerant (DT), lactose intolerant (LI) or n intolerant (NLDI, self-reported dairy intolerance, but lactose tolerant) ingested 750 mL of conventional milk (CM), lactose-free conventional milk (LF-CM) and a2 MilkTM (A2M) in a double-blind crossover randomised controlled trial. With CM resulting in greater postprandial circulating riboflavin concentrations in all subjects, this study showed lower concentrations in NLDI compared to LI individuals. Thus, despite milk being an important source of dietary riboflavin, the benefits may be hindered for older adults who frequently report gastrointestinal disturbances associated with dairy food consumption. Overall, the results of this thesis highlight the importance of absolute intake to improve postprandial B-vitamin circulatory concentrations, although it remains to be established whether an improved acute response also persists as an improved B-vitamin status in the elderly. The high responsiveness to both acute and long-term intake, particularly riboflavin, may suggest the potential for improving riboflavin status. However, the lack of response of the vitamer flavin mononucleotide (FMN) questions the cellular utilisation and body retention of riboflavin and thus further research is required in this area. The data generated from this thesis may also provide utility in the design of further research strategies aimed at improving B-vitamin status in the elderly.