How do we differentiate not demonise - Is there a role for healthier processed foods in an age of food insecurity? Proceedings of a roundtable event.

The 'ultra-processed food' (UPF) concept, with classification of foods by 'level of processing' rather than nutrient profiles, and its relationship with health outcomes, is currently a topic of debate among academics and increasingly referred to in the media. The British Nutrition Foundation convened a virtual roundtable on 6th July 2022 to gather views on the use of the term (and current definitions of) UPF for public health messaging, seeking to establish areas of consensus and disagreement and identify topics for further research. A small group of invited expert stakeholders attended, including representatives from academia, policy, behavioural science, communications, health, food science, retail and consumer interests. Participants' discussions clustered into cogent themes which included: problems with the use of definitions for UPF, the lack of causal evidence and defined mechanisms linking processing per se with poor health outcomes, and advice that may result in consumer confusion. There was agreement that many foods classified as UPF are high in fat, sugars and/or salt and public health messages should continue to focus on reducing these in the diet since it is unclear whether reported associations between high intakes of UPF and poor health reflect poorer dietary patterns (defined by nutrient intakes), and nutrient-health relationships are well established. Examples of misalignment were also highlighted (i.e. some foods are classified as UPF yet recommended in food-based dietary guidelines [featuring in healthy dietary patterns]). This raises challenges for consumer communication around UPF. Concern was also expressed about potential unintended consequences, particularly for vulnerable groups, where advice to avoid UPF could create stigma and guilt due to lack of time or facilities to prepare and cook meals from scratch. It could also impact on nutrient intakes, as some foods classified as UPF represent more affordable sources of important nutrients (e.g. packaged wholemeal bread). Discordance between the concept of UPF and current strategies to improve public health, such as reformulation, was also discussed. The group concluded that the use of the concept of UPF in UK policy (e.g. dietary guidelines) would be unhelpful at present. Overall, participants felt that it was more important to focus on providing practical advice around selection of healthier processed foods and making healthier foods more accessible rather than promoting the avoidance of UPF. The latter may act to demonise all foods classified as UPF by current definitions, including some affordable nutrient-dense foods.

Walnut consumption and health outcomes with public health relevance-a systematic review of cohort studies and randomized controlled trials published from 2017 to present.

CONTEXT: Considering the accumulation of recent studies investigating the health effects of walnut consumption, both including and beyond cardiovascular health effects, a systematic review of this literature to investigate the strength of the evidence is warranted. OBJECTIVE: To investigate associations between walnut consumption and outcomes with public health relevance (specifically all-cause mortality, type 2 diabetes, CVD, metabolic syndrome, obesity, cancer, neurological and mental health, musculoskeletal, gastrointestinal, and maternal disorders) and the effect on associated disease risk markers, reported in studies published from 2017 to present. DATA SOURCES: MEDLINE, FSTA, CENTRAL, and Scopus were searched from 1 January 2017 to 5 May 2021. DATA EXTRACTION: Human studies (cohort studies and RCTs) ≥3 weeks in duration comparing consumption of walnuts (whole, pieces, or 100% butter) to a control and measuring associations with relevant public health outcomes and disease risk markers were assessed. Key study characteristics were extracted independently by 2 investigators using a standardized table. The quality of the studies was assessed using the Cochrane Risk-of-Bias tool 2.0 and the Newcastle-Ottawa Scale. DATA ANALYSIS: Only 1 RCT was considered to be at low risk of bias for any of its outcomes. The cohort studies were considered to be of moderate or high quality. The results were synthesized using vote counting, based on the direction of effect. Thirty-three articles, 23 describing RCTs (walnut dose ∼10-99 g/day, 1,948 subjects) and 10 describing cohort studies (∼675,928 subjects), were included. Vote counting could be performed for the blood lipids, cardiovascular function, inflammation- and hemostatic-related factors, markers of glucose metabolism, and body weight and composition outcome groupings. The results are presented in effect direction plots. With respect to blood lipids, results from 8/8 RCTs favoured walnuts, in accordance with associations with a reduced risk of CVD suggested by cohort studies; results from 6/6 RCTs favoured control with respect to body weight and composition, although most of these effects were small. This was contrary to cohort study results suggesting small benefits of walnut consumption on body weight. There was no overall consistent direction of effect for cardiovascular function, markers of glucose metabolism, or inflammation- and hemostatic-related factors. CONCLUSIONS: Evidence published since 2017 is consistent with previous research suggesting that walnut consumption improves lipid profiles and is associated with reduced CVD risk. Evidence is accumulating in other areas, such as cognitive health, although more research is needed to draw firm conclusions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD4202122.

Impact of phenolic-rich olive leaf extract on blood pressure, plasma lipids and inflammatory markers: a randomised controlled trial.

PURPOSE: Dietary polyphenols have been demonstrated to favourably modify a number of cardiovascular risk markers such as blood pressure (BP), endothelial function and plasma lipids. We conducted a randomised, double-blind, controlled, crossover trial to investigate the effects of a phenolic-rich olive leaf extract (OLE) on BP and a number of associated vascular and metabolic measures. METHODS: A total of 60 pre-hypertensive [systolic blood pressure (SBP): 121-140 mmHg; diastolic blood pressure (DBP): 81-90 mmHg] males [mean age 45 (±SD 12.7 years, BMI 26.7 (±3.21) kg/m2] consumed either OLE (136 mg oleuropein; 6 mg hydroxytyrosol) or a polyphenol-free control daily for 6 weeks before switching to the alternate arm after a 4-week washout. RESULTS: Daytime [-3.95 (±SD 11.48) mmHg, p = 0.027] and 24-h SBP [-3.33 (±SD 10.81) mmHg, p = 0.045] and daytime and 24-h DBP [-3.00 (±SD 8.54) mmHg, p = 0.025; -2.42 (±SD 7.61) mmHg, p = 0.039] were all significantly lower following OLE intake, relative to the control. Reductions in plasma total cholesterol [-0.32 (±SD 0.70) mmol/L, p = 0.002], LDL cholesterol [-0.19 (±SD 0.56) mmol/L, p = 0.017] and triglycerides [-0.18 (±SD 0.48), p = 0.008] were also induced by OLE compared to control, whilst a reduction in interleukin-8 [-0.63 (±SD 1.13) pg/ml; p = 0.026] was also detected. Other markers of inflammation, vascular function and glucose metabolism were not affected. CONCLUSION: Our data support previous research, suggesting that OLE intake engenders hypotensive and lipid-lowering effects in vivo.

Apolipoprotein E (epsilon) genotype has a greater impact on apoB-48 than apoB-100 responses to dietary fat manipulation-insights from the SATgenε study.

SCOPE: To determine the contribution of intestinally and liver-derived lipoproteins to the postprandial plasma triacylglycerol (TAG) response in APOE3/E3 and E3/E4 individuals following chronic dietary fat manipulation. METHODS AND RESULTS: In sequential order, participants (n = 12 E3/E3, n = 11 E3/E4) followed low fat; high-fat, high-saturated fat (HSF); and HSF with 3.45 g/day docosahexaenoic acid (HSF-DHA) diets, each for 8 weeks. After each dietary period, an acute test meal with a macronutrient profile representative of the dietary intervention was consumed. Apolipoprotein (apo)B isoforms were determined in isolated TAG-rich lipoprotein fractions (Svedberg flotation rate (Sf ) > 400, Sf 60-400, and Sf 20-60) by specific ELISA. A genotype × meal/diet interaction for the Sf > 400 fraction apoB-48 response (p < 0.05) was observed, with higher concentrations reached after the low fat than HSF-DHA meal in E4 carriers. This finding was associated with a lower TAG content of the Sf > 400 particles. Fasting Sf 60-400 and 20-60 apoB-48 concentrations were also significantly higher in E4 carriers. No impact of genotype on the apoB-100 responses was evident. CONCLUSION: Our study revealed marked effects of dietary fat composition on the Sf > 400 apoB-48 response and particle TAG content in E4 carriers relative to the "wild-type" E3/E3 genotype, which suggest APOE genotype is a potential modulator of chylomicron particle synthesis.

Secoiridoids delivered as olive leaf extract induce acute improvements in human vascular function and reduction of an inflammatory cytokine: a randomised, double-blind, placebo-controlled, cross-over trial.

The leaves of the olive plant (Olea europaea) are rich in polyphenols, of which oleuropein and hydroxytyrosol (HT) are most characteristic. Such polyphenols have been demonstrated to favourably modify a variety of cardiovascular risk factors. The aim of the present intervention was to investigate the influence of olive leaf extract (OLE) on vascular function and inflammation in a postprandial setting and to link physiological outcomes with absorbed phenolics. A randomised, double-blind, placebo-controlled, cross-over, acute intervention trial was conducted with eighteen healthy volunteers (nine male, nine female), who consumed either OLE (51 mg oleuropein; 10 mg HT), or a matched control (separated by a 4-week wash out) on a single occasion. Vascular function was measured by digital volume pulse (DVP), while blood collected at baseline, 1, 3 and 6 h was cultured for 24 h in the presence of lipopolysaccharide in order to investigate effects on cytokine production. Urine was analysed for phenolic metabolites by HPLC. DVP-stiffness index and ex vivo IL-8 production were significantly reduced (P< 0.05) after consumption of OLE compared to the control. These effects were accompanied by the excretion of several phenolic metabolites, namely HT and oleuropein derivatives, which peaked in urine after 8-24 h. The present study provides the first evidence that OLE positively modulates vascular function and IL-8 production in vivo, adding to growing evidence that olive phenolics could be beneficial for health.

Greater impact of dietary fat manipulation than apolipoprotein E genotype on ex vivo cytokine production - insights from the SATgenε study.

Apolipoprotein E (APOE) genotype is believed to play an important role in cardiovascular risk. APOE4 carriers have been associated with higher blood lipid levels and a more pro-inflammatory state compared with APOE3/E3 individuals. Although dietary fat composition has been considered to modulate the inflammatory state in humans, very little is known about how APOE genotype can impact on this response. In a follow-up to the main SATgenε study, we aimed to explore the effects of APOE genotype, as well as, dietary fat manipulation on ex vivo cytokine production. Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). Concentrations of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha were measured in WBC supernatant samples after stimulation for 24h with either 0.05 or 1µg/ml of bacterial lipopolysaccharide (LPS). Cytokine levels were not influenced by genotype, whereas, dietary fat manipulation had a significant impact on TNF-α and IL-10 production; TNF-α concentration was higher after consumption of the HSF diet compared with baseline and the LF diet (P<0.05), whereas, IL-10 concentration was higher after the LF diet compared with baseline (P<0.05). In conclusion, our study has revealed the amount and type of dietary fat can significantly modulate the production of TNF-α and IL-10 by ex vivo LPS-stimulated WBC samples obtained from normolipidaemic subjects.

APOE genotype influences triglyceride and C-reactive protein responses to altered dietary fat intake in UK adults.

BACKGROUND: The response of plasma lipids to dietary fat manipulation is highly heterogeneous, with some indications that APOE genotype may be important. OBJECTIVE: The objective was to use a prospective recruitment approach to determine the effect of dietary fat quantity and composition on both lipid and nonlipid cardiovascular disease biomarkers according to APOE genotype. DESIGN: Participants had a mean (±SD) age of 51 ± 9 y and a BMI (in kg/m²) of 26.0 ± 3.8 (n = 44 E3/E3, n = 44 E3/E4) and followed a sequential dietary intervention (the SATgenε study) in which they were assigned to a low-fat diet, a high-fat high-SFA (HSF) diet, and the HSF diet with 3.45 g DHA/d (HSF-DHA), each for 8 wk. Fasting blood samples were collected at the end of each intervention arm. RESULTS: An overall diet effect was evident for all cholesterol fractions (P < 0.01), with no significant genotype × diet interactions observed. A genotype × diet interaction (P = 0.033) was evident for plasma triglycerides, with 17% and 30% decreases in APOE3/E3 and APOE3/E4 individuals after the HSF-DHA diet relative to the low-fat diet. A significant genotype × diet interaction (P = 0.009) was also observed for C-reactive protein (CRP), with only significant increases in concentrations after the HSF and HSF-DHA diets relative to the low-fat diet in the APOE3/E4 group (P < 0.015). CONCLUSIONS: Relative to the wild-type APOE3/E3 group, our results indicate a greater sensitivity of fasting triglycerides and CRP to dietary fat manipulation in those with an APOE3/E4 genotype (25% population), with no effect of this allelic profile on cholesterol concentrations.

Dietary fat manipulation has a greater impact on postprandial lipid metabolism than the apolipoprotein E (epsilon) genotype-insights from the SATgenε study.

SCOPE: Our aim was to determine the effects of chronic dietary fat manipulation on postprandial lipaemia according to apolipoprotein (APO)E genotype. METHODS AND RESULTS: Men (mean age 53 (SD 9) years), prospectively recruited for the APOE genotype (n = 12 E3/E3, n = 11 E3/E4), were assigned to a low fat (LF), high fat, high-saturated fat (HSF), and HSF diet with 3.45 g/day docosahexaenoic acid (HSF-DHA), each for an 8-week period in the same order. At the end of each dietary period, a postprandial assessment was performed using a test meal with a macronutrient profile representative of that dietary intervention. A variable postprandial plasma triacylglycerol (TAG) response according to APOE genotype was evident, with a greater sensitivity to the TAG-lowering effects of DHA in APOE4 carriers (p ≤ 0.005). There was a lack of an independent genotype effect on any of the lipid measures. In the groups combined, dietary fat manipulation had a significant impact on lipids in plasma and Svedberg flotation rate (S(f) ) 60-400 TAG-rich lipoprotein fraction, with lower responses following the HSF-DHA than HSF intervention (p < 0.05). CONCLUSION: Although a modest impact of APOE genotype was observed on the plasma TAG profile, dietary fat manipulation emerged as a greater modulator of the postprandial lipid response in normolipidaemic men.

SATgenε dietary model to implement diets of differing fat composition in prospectively genotyped groups (apoE) using commercially available foods.

Response to dietary fat manipulation is highly heterogeneous, yet generic population-based recommendations aimed at reducing the burden of CVD are given. The APOE epsilon genotype has been proposed to be an important determinant of this response. The present study reports on the dietary strategy employed in the SATgenε (SATurated fat and gene APOE) study, to assess the impact of altered fat content and composition on the blood lipid profile according to the APOE genotype. A flexible dietary exchange model was developed to implement three isoenergetic diets: a low-fat (LF) diet (target composition: 24 % of energy (%E) as fat, 8 %E SFA and 59 %E carbohydrate), a high-saturated fat (HSF) diet (38 %E fat, 18 %E SFA and 45 %E carbohydrate) and a HSF-DHA diet (HSF diet with 3 g DHA/d). Free-living participants (n 88; n 44 E3/E3 and n 44 E3/E4) followed the diets in a sequential design for 8 weeks, each using commercially available spreads, oils and snacks with specific fatty acid profiles. Dietary compositional targets were broadly met with significantly higher total fat (42·8 %E and 41·0 %E v. 25·1 %E, P ≤ 0·0011) and SFA (19·3 %E and 18·6 %E v. 8·33 %E, P ≤ 0·0011) intakes during the HSF and HSF-DHA diets compared with the LF diet, in addition to significantly higher DHA intake during the HSF-DHA diet (P ≤ 0·0011). Plasma phospholipid fatty acid analysis revealed a 2-fold increase in the proportion of DHA after consumption of the HSF-DHA diet for 8 weeks, which was independent of the APOE genotype. In summary, the dietary strategy was successfully implemented in a free-living population resulting in well-tolerated diets which broadly met the dietary targets set.

Long chain n-3 PUFA-rich meal reduced postprandial measures of arterial stiffness.

BACKGROUND & AIMS: The consumption of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) is known to be cardio-protective. Data on the influence of LC n-3 PUFA on arterial stiffness in the postprandial state is limited. The aim of this study was to investigate the acute effects of a LC n-3 PUFA-rich meal on measures of arterial stiffness. METHODS: Twenty-five healthy subjects (12 men, 13 women) received a control and a LC n-3 PUFA-rich meal on two occasions in a random order. Arterial stiffness was measured at baseline, 30, 60, 90, 120, 180 and 240 min after meal consumption by pulse wave analysis and digital volume pulse to derive an augmentation index and a stiffness index respectively. Blood samples were taken for measurement of lipids, glucose and insulin. RESULTS: Consumption of the LC n-3 PUFA-rich meal had an attenuating effect on augmentation index (P=0.02) and stiffness index (P=0.03) compared with the control meal. A significant treatment effect (P=0.036) was seen for plasma non-esterified fatty acids concentrations. CONCLUSIONS: These data indicate that acute LC n-3 PUFA-rich meal consumption can improve postprandial arterial stiffness. This has important implications for the beneficial properties of LC n-3 PUFA and cardiovascular risk reduction.

Synthesis and enzymatic evaluation of pyridinium-substituted uracil derivatives as novel inhibitors of thymidine phosphorylase.

A series of water soluble N(1)- and C(6)-substituted uracil pyridinium compounds were prepared as potential inhibitors of thymidine phosphorylase (TP). The C(6)-uracil substituted derivatives were the most active. 1-[(5-Chloro-2,4-dihydroxypyrimidin-6-yl)methyl]pyridinium chloride, was identified as the best inhibitor being 5-fold more potent than the known inhibitor, 6-amino-5-bromouracil.