Changes in vitamin biomarkers during a 2-year intervention trial involving increased fruit and vegetable consumption by free-living volunteers

Peer reviewedPublisher PD

The effect of short-term kaempferol exposure on reactive oxygen levels and integrity of human (HL-60) leukaemic cells

AbstractFlavonoids may be a principal contributor to the cancer preventative activity of fruit- and vegetable-rich diets and there is interest in their use as dietary supplements. However, there is potential conflict between the cytoprotective and cytotoxic activities of flavonoids, and their efficacy as anti-cancer agents is unresolved. Here, the integrity and survival of HL-60 promyelocytic leukaemia cells following short-term (90 min) exposure to the dietary abundant flavonoid kaempferol (1–100 μM) is reported. Supplementation initially decreased reactive oxygen levels but, paradoxically, a dose-dependent increase in single-strand DNA breakage occurred. However, there was no increase in oxidised DNA purines or membrane damage. Following a 24-h recovery period in non-kaempferol supplemented media, DNA single-strand breakage had declined and kaempferol exposed and control cultures possessed similar reactive oxygen levels. A reduction in 3H-thymidine incorporation occurred with ≥10 μM kaempferol. One hundred micromolar kaempefrol increased the proportion of cells in G2-M phase, the proportion of cells with a sub-G1 DNA content and enhanced ‘active’ caspase-3 expression but only induced a loss of mitochondrial membrane potential within a minority of cells. The relevance of induced DNA damage within a non-overtly oxidatively stressed environment to the disease preventative and therapeutic use of kaempferol is discussed

Differential effects of nutritional folic acid deficiency and moderate hyperhomocysteinemia on aortic plaque formation and genome-wide DNA methylation in vascular tissue from ApoE-/- mice

Low folate intake is associated with vascular disease. Causality has been attributed to hyperhomocysteinemia. However, human intervention trials have failed to show the benefit of homocysteine-lowering therapies. Alternatively, low folate may promote vascular disease by deregulating DNA methylation. We investigated whether folate could alter DNA methylation and atherosclerosis in ApoE null mice. Mice were fed one of six diets (n = 20 per group) for 16 weeks. Basal diets were either control (C; 4% lard) or high fat (HF; 21% lard and cholesterol, 0.15%) with different B-vitamin compositions: (1) folic acid and B-vitamin replete, (2) folic acid deficient (−F), (3) folic acid, B6 and B12 deficient (−F−B). −F diets decreased plasma (up to 85%; P < 0.05), whole blood (up to 70%; P < 0.05), and liver folate (up to 65%; P < 0.05) and hepatic SAM/SAH (up to 80%; P < 0.05). −F−B diets reduced plasma (up to 76%; P < 0.05), whole blood (up to 72%; P < 0.05), and liver B12 (up to 39%; P < 0.05) and hepatic SAM/SAH (up to 90%; P < 0.05). −F increased homocysteine 2-fold, while −F−B increased homocysteine 3.6- and 6.8-fold in the C and HF groups (P < 0.05). Plaque formation was increased 2-fold (P < 0.0001) in mice fed a HF diet. Feeding a HF–F diet increased lesion formation by 17% (P < 0.05). There was no change in 5-methyldeoxycytidine in liver or vascular tissue (aorta, periadventitial tissue and heart). These data suggest that atherogenesis is not associated with genome-wide epigenetic changes in this animal model

Oral human papillomavirus infection in England and associated risk factors: a case control study.

Objectives - This study was conducted to determine the prevalence of and associated risk factors for infection with oral high-risk human papillomavirus (HR-HPV) in adult participants within England, and to explore any association with oral mucosal buccal epithelial cell and whole blood folate concentration. Design - This was an observational study to determine oral HR-HPV prevalence in the study population. A case-control study was performed to explore the association between infection and folate status. Setting - This study was conducted in Sheffield, United Kingdom between April 2013 and August 2014. Participants - Seven hundred participants, aged 18-60 yr, were recruited from university students (n=179), university and hospital staff (n=163), dental hospital patients (n=13), Sexual Health Sheffield patients (n=122) and the general public (n=223). Interventions - Participants completed a lifestyle and sexual behaviour questionnaire, provided an oral rinse and gargle sample for the detection of oral HR-HPV and an oral mucosal buccal epithelial cell sample for the measurement of oral mucosal buccal epithelial cell folate. A blood sample was collected for measurement of whole blood folate concentration. Outcome measures - The prevalence of oral HR-HPV infection in the study population was the primary outcome measure. Secondary outcome measures included associations between risk factors, folate status and infection. Results - The prevalence of oral HR-HPV infection in this cohort was 2.2% (15/680) with 0.7% (5/680) positive for HPV16 or HPV18. Twenty samples were excluded due to insufficient material for HPV detection. Participants with oral HR-HPV infection were more likely to be a former smoker, and have a greater number of sexual and oral sexual partners. Folate status was not linked to likelihood of HPV infection. Conclusions - The prevalence of oral infection with HR-HPV in adult men and women in Sheffield in the north of England was low. Smoking and sexual behaviour were associated with HR-HPV positivity

Effect of increasing fruit and vegetable intake by dietary intervention on nutritional biomarkers and attitudes to dietary change : a randomised trial

This work was funded by The Scottish Government Rural and Environmental Science and Analytical Sciences Division (RESAS) and supported by the Rank Prize Funds.Peer reviewedPublisher PD

Links between the rumen microbiota, methane emissions and feed efficiency of finishing steers offered dietary lipid and nitrate supplementation

peer-reviewedRuminant methane production is a significant energy loss to the animal and major contributor to global greenhouse gas emissions. However, it also seems necessary for effective rumen function, so studies of anti-methanogenic treatments must also consider implications for feed efficiency. Between-animal variation in feed efficiency represents an alternative approach to reducing overall methane emissions intensity. Here we assess the effects of dietary additives designed to reduce methane emissions on the rumen microbiota, and explore relationships with feed efficiency within dietary treatment groups. Seventy-nine finishing steers were offered one of four diets (a forage/concentrate mixture supplemented with nitrate (NIT), lipid (MDDG) or a combination (COMB) compared to the control (CTL)). Rumen fluid samples were collected at the end of a 56 d feed efficiency measurement period. DNA was extracted, multiplexed 16s rRNA libraries sequenced (Illumina MiSeq) and taxonomic profiles were generated. The effect of dietary treatments and feed efficiency (within treatment groups) was conducted both overall (using non-metric multidimensional scaling (NMDS) and diversity indexes) and for individual taxa. Diet affected overall microbial populations but no overall difference in beta-diversity was observed. The relative abundance of Methanobacteriales (Methanobrevibacter and Methanosphaera) increased in MDDG relative to CTL, whilst VadinCA11 (Methanomassiliicoccales) was decreased. Trimethylamine precursors from rapeseed meal (only present in CTL) probably explain the differences in relative abundance of Methanomassiliicoccales. There were no differences in Shannon indexes between nominal low or high feed efficiency groups (expressed as feed conversion ratio or residual feed intake) within treatment groups. Relationships between the relative abundance of individual taxa and feed efficiency measures were observed, but were not consistent across dietary treatments

Consumption of a recommended serving of wheat bran cereals significantly increases human faecal butyrate levels in healthy volunteers and reduces markers of inflammation ex vivo.

Wheat bran cereals are an important source of dietary fibre. The aim of the study was to investigate if a high intake (120 g) of fibre rich breakfast cereal (which delivers the UK Government guidelines for fibre intake in one serving but is three-fold higher than the manufacturers recommended serving) has additional potential health benefits compared to the recommended serving (40 g, containing 11 g of dietary fibre). To assess this, the study determined the short chain fatty acid (SCFA) profiles in human faecal, urine and plasma samples after consumption of two different servings of fibre-rich cereal. Inhibition of prostanoid production was measured (ex vivo) in human colonic fibroblast cells after cytokine (IL-1β) inflammation stimulation. Eight healthy volunteers, 18-55 years old; BMI (18-30 kg/m2) consumed the wheat bran-rich "ready to eat cereal", at both the high (120 g) serving and recommended (40 g) serving. Faecal, urine and plasma samples were collected at baseline, throughout the five-hour intervention period and approximately 24 hours following consumption. Faecal butyrate showed the largest increase (p < 0.05) of more than a two-fold change following the consumption of the recommended serving of wheat bran cereal (from 13.95 ± 9.17 to 31.63 ± 20.53 mM) and no significant change following the higher serving (from 21.96 ± 11.03 to 22.9 ± 12.69 mM). ANOVA analysis also found a weak serving effect (p = 0.046) of the portion size (high vs. recommended) only for butyrate in urine 24 hours after consumption of the bran cereal. The physiological nutritionally relevant concentrations of faecal SCFAs, as determined in the volunteers' faecal samples showed significant anti-inflammatory activity or the individual faecal SCFAs; acetate (p < 0.001), propionate (p < 0.001) and butyrate (p < 0.01), as well as in combination. Plasma folate was also increased after consumption of both wheat bran servings and was significant (p = 0.037) at the three-hour time point following consumption of the high wheat bran serving. The consumption of the recommended serving (40 g) of wheat bran cereal increased the total microbial SCFAs levels (from 96.88 to 136.96 mM) compared to the higher serving (120 g) (from 110.5 to 117.64 mM) suggesting that the intake of the higher portion size is likely to promote a faecal bulking effect and thereby decrease colonic SCFA levels. These data indicate that consumption of the recommended serving of wheat bran cereal serving would therefore be sufficient to promote microbial butyrate formation, reduce colonic inflammation and increase plasma folate levels in humans

Season, storage and extraction method impact on the phytochemical profile of Terminalia ivorensis

Acknowledgements The authors would like to thank the laboratory technical staff of the School of Pharmacy and Life Sciences, Robert Gordon University (especially Stephen Williamson and Chris Fletcher) and University of Aberdeen, the Analytical Department of Rowett Institute (especially Gary J. Duncan) for their support. Funding Ghana Education Trust Fund (GETFund) for providing funding for the studies.Peer reviewedPublisher PD

Nutritional B vitamin deficiency alters the expression of key proteins associated with vascular smooth muscle cell proliferation and migration in the aorta of atherosclerotic apolipoprotein E null mice.

Low B vitamin status is linked with human vascular disease. We employed a proteomic and biochemical approach to determine whether nutritional folate deficiency and/or hyperhomocysteinemia altered metabolic processes linked with atherosclerosis in ApoE null mice. Animals were fed either a control fat (C; 4 % w/w lard) or a high-fat [HF; 21 % w/w lard and cholesterol (0/15 % w/w)] diet with different B vitamin compositions for 16 weeks. Aorta tissue was prepared and global protein expression, B vitamin, homocysteine and lipoprotein status measured. Changes in the expression of aorta proteins were detected in response to multiple B vitamin deficiency combined with a high-fat diet (P < 0.05) and were strongly linked with lipoprotein concentrations measured directly in the aorta adventitia (P < 0.001). Pathway analysis revealed treatment effects in the aorta-related primarily to cytoskeletal organisation, smooth muscle cell adhesion and invasiveness (e.g., fibrinogen, moesin, transgelin, vimentin). Combined B vitamin deficiency induced striking quantitative changes in the expression of aorta proteins in atherosclerotic ApoE null mice. Deregulated expression of these proteins is associated with human atherosclerosis. Cellular pathways altered by B vitamin status included cytoskeletal organisation, cell differentiation and migration, oxidative stress and chronic inflammation. These findings provide new insight into the molecular mechanisms through which B vitamin deficiency may accelerate atherosclerosis