The term phyto-oestrogen encompasses isoflavone compounds, such as genistein and daidzein, found predominantly in soya products and the lignans, such as matairesinol and secoisolariciresinol, found in many fruits, cereals and in flaxseed. There is evidence that they have potential health benefits in man particularly against hormone-dependent diseases such as breast and prostate cancers and osteoporosis. This has led to intense interest in their absorption and biotransformation in man. The metabolism of isoflavones and lignans in animals and man is complex and involves both mammalian and gut microbial processes. Isoflavones are present predominantly as glucosides in most commercially available soya products; there is evidence that they are not absorbed in this form and that their bioavailability requires initial hydrolysis of the sugar moiety by intestinal beta-glucosidases. After absorption, phyto-oestrogens are reconjugated predominantly to glucuronic acid and to a lesser degree to sulphuric acid. Only a small portion of the free aglycone has been detected in blood, demonstrating that the rate of conjugation is high. There is extensive further metabolism of isoflavones (to equol and O-desmethylangolensin) and lignans (to enterodiol and enterolactone) by gut bacteria. In human subjects, even those on controlled diets, there is large interindividual variation in the metabolism of isoflavones and lignans, particularly in the production of the gut bacterial metabolite equol (from daidzein). Factors influencing absorption and metabolism of phyto-oestrogens include diet and gut microflora.

The potential protective roles of folate and the metabolically related B-vitamins (vitamins B12, B6 and riboflavin) in diseases of ageing are of increasing research interest. The most common cause of folate and riboflavin deficiencies in older people is low dietary intake, whereas low B12 status is primarily associated with food-bound malabsorption, while sub-optimal vitamin B6 status is attributed to increased requirements in ageing. Observational evidence links low status of folate and the related B-vitamins (and/or elevated concentrations of homocysteine) with a higher risk of degenerative diseases including cardiovascular disease (CVD), cognitive dysfunction and osteoporosis. Deficient or low status of these B-vitamins alone or in combination with genetic polymorphisms, including the common MTHFR 677 C → T polymorphism, could contribute to greater disease risk in ageing by causing perturbations in one carbon metabolism. Moreover, interventions with the relevant B-vitamins to optimise status may have beneficial effects in preventing degenerative diseases. The precise mechanisms are unknown but many have been proposed involving the role of folate and the related B-vitamins as co-factors for one-carbon transfer reactions, which are fundamental for DNA and RNA biosynthesis and the maintenance of methylation reactions. This review will examine the evidence linking folate and related B-vitamins with health and disease in ageing, associated mechanisms and public health implications.

This study demonstrated significant associations between low vitamin D status and markers of inflammation (including the ratio of IL-6 to IL-10) within elderly adults. These findings suggest that an adequate vitamin D status may be required for optimal immune function, particularly within the older adult population.

Globally populations are ageing. By 2050, it is estimated that there will be two billion people aged 60 years or over, of which 131 million are projected to be affected by dementia, while depression is predicted to be the second leading cause of disability worldwide by 2020. Preventing or delaying the onset of these disorders should therefore be a public health priority. There is some evidence linking certain dietary patterns, particularly the Mediterranean diet, with a reduced risk of dementia and depression. Specific dietary components have also been investigated in relation to brain health, with emerging evidence supporting protective roles for n-3 PUFA, polyphenols, vitamin D and B-vitamins. At this time, the totality of evidence is strongest in support of a role for folate and the metabolically related B-vitamins (vitamin B12, vitamin B6 and riboflavin) in slowing the progression of cognitive decline and possibly reducing the risk of depression in ageing. Future studies incorporating new technologies, such as MRI and magnetoencephalography, offer much promise in identifying effective nutrition interventions that could reduce the risk of cognitive and mental disorders. This review will explore the ageing brain and the emerging evidence linking diet and specific nutrients with cognitive function and depression in ageing, with the potential to develop strategies that could improve quality of life in our ageing population.

These results show that voluntary food fortification is associated with a substantial increase in dietary intake and biomarker status of folate and metabolically related B vitamins with potential beneficial effects on health. However, those who do not consume fortified foods regularly may have insufficient B vitamin status to achieve the known and potential health benefits.

There is considerable interest in plasma homocysteine (tHcy) as a CVD risk factor. Although the secondary prevention trials published to date have been inconclusive in confirming a benefit of tHcy-lowering treatment with B-vitamins on CVD events generally, such studies are widely recognised to have been insufficiently powered to detect a significant effect for the predicted magnitude of association between tHcy and heart disease risk, and therefore cannot be interpreted as evidence that no relationship exists. In fact, a recent meta-analysis of clinical trials has confirmed that folic acid supplementation reduces the risk of stroke, particularly in individuals without a history of stroke. Evidence supporting a causal relationship between elevated tHcy and heart disease also comes from genetic studies. The most important genetic determinant of tHcy in the general population is the common C677T variant in methylenetetrahydrofolate reductase (MTHFR) that results in higher tHcy. Individuals with the homozygous mutant (TT) genotype have a significantly higher (14-21 %) risk of heart disease. Plasma tHcy is very responsive to intervention with the B-vitamins required for its metabolism, in particular folic acid, and to a lesser extent vitamins B 12 and B 6 . Thus, although primarily aimed at reducing neural-tube defects, folic acid fortification may have an important role in the primary prevention of CVD via tHcy lowering. Besides folate, riboflavin is required as a cofactor for MTHFR and enhanced riboflavin status results in a marked lowering in tHcy specifically in individuals with the TT genotype, presumably by neutralising the variant form of the enzyme. About 10 % of the UK and Irish populations have the TT genotype. In the present paper the potential role of folate and related B-vitamins in the primary prevention of CVD and the implications for nutrition policy are explored. B-vitamins: Folate: Homocysteine: CVD Elevated homocysteine as a risk factor for CVDEvidence from numerous prospective and retrospective case-control studies has emerged in recent years to link elevated plasma homocysteine (tHcy) levels with an increased risk of CVD. Meta-analyses of prospective studies have predicted that lowering tHcy by 3 mmol/l (or a reduction of 25% based on an average tHcy of 12 mmol/l) would reduce the risk of heart disease by 11-16 % and stroke by 19-24 % (1,2) . Although none of the secondary prevention trials published in more recent years have been able to confirm the benefit of tHcy-lowering therapy on CVD events generally (3)(4)(5) , it should not be assumed that no relationship exists. It is now generally recognised that these trials lacked sufficient statistical power to detect an effect for the predicted magnitude of association between tHcy and heart disease (6) . In support of this viewpoint, a clear benefit in reducing stroke was shown in one of the previously mentioned 'negative' trials, although this result was not explicit in the conclusions (4) . Moreover, evidence just published from a meta-analysis o...

A compromised vitamin B12 status is common in older people despite dietary intakes that typically far exceed current recommendations. The maintenance of an optimal status of vitamin B12 is not only dependent on adequate dietary intake but more critically on effective absorption which diminishes with age. The measurement of vitamin B12 is complicated by the lack of a gold standard assay. There are a number of direct and functional indicators of vitamin B12 status; however, none of these are without limitations and should be used in combination. Vitamin B12 is of public health importance, not only because deficiency leads to megaloblastic anaemia and irreversible nerve damage, but also because emerging evidence links low B12 to an increased risk of a number of age-related diseases, including cardiovascular disease, cognitive dysfunction, dementia and osteoporosis. Furthermore, there are concerns relating to potential adverse effects for older adults with low vitamin B12 status of over-exposure to folic acid in countries where there is mandatory fortification of food with folic acid. The aim of this review is to examine the known and emerging issues related to vitamin B12 in ageing, its assessment and inter-relationship with folate.

The urinary excretion of soya isoflavones and gut microflora metabolites was investigated in infants and children who had been fed soyabased infant formulas in early infancy. These infants and children were compared with cows'-milk formula-fed controls, to determine at what age gut microflora metabolism of daidzein to equol and/or O-desmethylangolensin (O-DMA) was established, and whether exposure to isoflavones in early infancy influences their metabolism at a later stage of development. Sixty infants and children (aged 4 months -7 years) participated in the study; thirty in each of the soya and control groups. There were four age groups. These were: 4 -6 months (seven in the soya group and seven in the control group); 7 -12 months (seven in the soya group and nine in the control group); 1 -3 years (six in the soya group and eight in the control group); 3 -7 years (ten in the soya group and six in the control group). Urine samples were collected to measure isoflavonoids by MS, and faecal samples were collected to measure gut-health-related bacterial composition, by fluorescent in situ hybridisation with oligonucleotide probes, and metabolic activity. A soya challenge (typically a soya yoghurt alternative product containing 4·8 g soya protein and on average 22 mg total isoflavones) was given to control-group infants (. 6 months) and children, and also to soya-group children that were no longer consuming soya, to determine their ability to produce equol and/or O-DMA. Urinary genistein, daidzein and glycitein were detected in all infants (4 -6 months) fed soya-based infant formula; O-DMA was detected in 75 % of infants but equol was detected in only 25 %. In the controls (4 -6 months), urinary isoflavonoids were very low or not detected. In the older age groups (7 months -7 years), O-DMA was found in the urine samples of 75 % of the soya group and 50 % of the controls, after the soya challenge. Equol excretion was detected in 19 % of the soya-group infants and children, and in only 5 % of the controls. However, in the oldest (3 -7 years) children, the proportion excreting O-DMA and equol was similar in both groups. Faecal bacterial numbers for bifidobacteria (P, 0·001), bacteroides and clostridia (P, 0·05) were significantly lower for the soya group compared with the control group. There appears to be no lasting effect of early-life isoflavone exposure on isoflavone metabolism. Soya isoflavone metabolism: Equol: Soya-based infant formula: Gut bacterial microflora