The functional effects of folate within C1 metabolism involve interrelationships with vitamin B12, vitamin B6 and riboflavin, and related gene–nutrient interactions. These B vitamins have important roles throughout life, from pregnancy, through childhood, to middle and older age. Achieving optimal nutritional status for preventing folate-related disease is challenging, however, primarily as a result of the poor stability and incomplete bioavailability of folate from natural food sources when compared with the synthetic vitamin form, folic acid. Thus, in European countries, measures to prevent neural tube defects (NTD) have been largely ineffective because of the generally poor compliance of women with folic acid supplementation as recommended before and in early pregnancy. In contrast, countries worldwide with mandatory folic acid fortification policies have experienced marked reductions in NTD. Low vitamin B12 status is associated with increased risk of cognitive dysfunction, CVD and osteoporosis. Achieving optimal B12 status can be problematic for older people, however, primarily owing to food-bound B12 malabsorption which leads to sub-clinical deficiency even with high dietary B12 intakes. Optimising B-vitamin intake may be particularly important for sub-populations with impaired folate metabolism owing to genetic characteristics, most notably the 677C→T variant in the gene encoding the enzyme methylenetetrahydrofolate reductase (MTHFR). This common folate polymorphism is linked with several adverse health outcomes, including stroke, however, recent evidence has identified its novel interaction with riboflavin (the MTHFR cofactor) in relation to blood pressure and risk of developing hypertension. This review addresses why and how the optimal status of folate-related B vitamins should be achieved through the lifecycle.

The term ‘sweeteners’ encompasses both nutritive and non-nutritive sweeteners, which when added to food/beverages, can enhance the flavour and other functional properties of food/beverage products. This review considers how dietary biomarker approaches may enhance current understanding of nutritive sweetener (namely free sugars) and non-nutritive or low-energy sweetener (LES) intakes and how these may impact health. Recent public health strategies to reduce free sugar consumption will help contribute to challenging sugar intake targets. Robust evaluation is needed to determine the effectiveness of these approaches to reducing free sugar consumption. LES provides a sweet taste without the addition of appreciable energy and can help maintain the palatability of reformulated products. All LES undergo rigorous safety evaluations prior to approval for use. Whilst intervention data suggest LES can be beneficial for health (relating to weight status and glycaemic control), debate persists on their use and findings from population-based research are mixed, in part because of potential contributing factors such as reverse causality. Additionally, assessments often consider only certain sources of LES (e.g. LES-beverages) and/or LES as a homogeneous group despite differing biological fates, thus not adequately capturing intakes of individual LES or allowing for reliable estimation of overall intakes. Urinary biomarker approaches developed/investigated for sweetener consumption have the potential to overcome existing limitations of dietary data by providing more objective intake data, thereby enhancing population-based research. In conclusion, such biomarker approaches to the concomitant study of free sugars and LES intakes are timely and represent interesting developments in an area of significant public health interest.