Archive

Research Area: Nutrient and Bioactive Composition

Mediterranean-style diet in pregnant women with metabolic risk factors (ESTEEM): A pragmatic multicentre randomised trial.

H Al Wattar, B., J. Dodds, A. Placzek, L. Beresford, E. Spyreli, A. Moore, F.J. Carreras, F. Austin, N. Murugesu, T.J. Roseboom, M. Bes-Rastrollo, 2019. Mediterranean-style diet in pregnant women with metabolic risk factors (ESTEEM): A pragmatic multicentre randomised trial. PLoS Med. 16(7):e1002857. doi:10.1371/journal.pmed.1002857

Background: Pregnant women with metabolic risk factors are at high risk of complications. We aimed to assess whether a Mediterranean-style diet reduces adverse pregnancy outcomes in high-risk women. Methods and findings: We conducted a multicentre randomised trial in 5 maternity units (4 in London and 1 in Birmingham) between 12 September 2014 and 29 February 2016. We randomised inner-city pregnant women with metabolic risk factors (obesity, chronic hypertension, or hypertriglyceridaemia) to a Mediterranean-style diet with high intake of nuts, extra virgin olive oil, fruits, vegetables, non-refined grains, and legumes; moderate to high consumption of fish; low to moderate intake of poultry and dairy products; low intake of red and processed meat; and avoidance of sugary drinks, fast food, and food rich in animal fat versus usual care. Participants received individualised dietary advice at 18, 20, and 28 weeks’ gestation. The primary endpoints were composite maternal (gestational diabetes or preeclampsia) and composite offspring (stillbirth, small for gestational age, or admission to neonatal care unit) outcomes prioritised by a Delphi survey. We used an intention-to-treat (ITT) analysis with multivariable models and identified the stratification variables and prognostic factors a priori. We screened 7,950 and randomised 1,252 women. Baseline data were available for 593 women in the intervention (93.3% follow-up, 553/593) and 612 in the control (95.6% follow-up, 585/612) groups. Over a quarter of randomised women were primigravida (330/1,205; 27%), 60% (729/1,205) were of Black or Asian ethnicity, and 69% (836/1,205) were obese. Women in the intervention arm consumed more nuts (70.1% versus 22.9%; adjusted odds ratio [aOR] 6.8, 95% confidence interval [CI] 4.3–10.6, p ≤ 0.001) and extra virgin olive oil (93.2% versus 49.0%; aOR 32.2, 95% CI 16.0–64.6, p ≤ 0.001) than controls; increased their intake of fish (p < 0.001), white meat (p < 0.001), and pulses (p = 0.05); and reduced their intake of red meat (p < 0.001), butter, margarine, and cream (p < 0.001). There was no significant reduction in the composite maternal (22.8% versus 28.6%; aOR 0.76, 95% CI 0.56–1.03, p = 0.08) or composite offspring (17.3% versus 20.9%; aOR 0.79, 95% CI 0.58–1.08, p = 0.14) outcomes. There was an apparent reduction in the odds of gestational diabetes by 35% (aOR 0.65, 95% CI 0.47–0.91, p = 0.01) but not in other individual components of the composite outcomes. Mothers gained less gestational weight (mean 6.8 versus 8.3 kg; adjusted difference −1.2 Kg, 95% CI −2.2 to −0.2, p = 0.03) with intervention versus control. There was no difference in any of the other maternal and offspring complications between both groups. When we pooled findings from the Effect of Simple, Targeted Diet in Pregnant Women With Metabolic Risk Factors on Pregnancy Outcomes (ESTEEM) trial with similar trials using random effects meta-analysis, we observed a significant reduction in gestational diabetes (odds ratio [OR] 0.67, 95% CI 0.53–0.84, I2 = 0%), with no heterogeneity (2 trials, 2,397 women). The study’s limitations include the use of participant reported tools for adherence to the intervention instead of objective biomarkers. Conclusions: A simple, individualised, Mediterranean-style diet in pregnancy did not reduce the overall risk of adverse maternal and offspring complications but has the potential to reduce gestational weight gain and the risk of gestational diabetes.

The beneficial effects of Mediterranean diet over low-fat diet may be mediated by decreasing hepatic fat content.

Gepner, Y., I. Shelef, O. Komy, N. Cohen, D. Schwarzfuchs, N. Bril, M. Rein, D. Serfaty, S. Kenigsbuch, H. Zelicha, A.Y. Meir, 2019. The beneficial effects of Mediterranean diet over low-fat diet may be mediated by decreasing hepatic fat content. J Hepatol. 71(2):379-388.

Background & Aim: It is unclear if a reduction in hepatic fat content (HFC) is a major mediator of the cardiometabolic benefit of lifestyle intervention, and whether it has prognostic significance beyond the loss of visceral adipose tissue (VAT). In the present sub-study, we hypothesized that HFC loss in response to dietary interventions induces specific beneficial effects independently of VAT changes. Methods: In an 18-month weight-loss trial, 278 participants with abdominal obesity/dyslipidemia were randomized to low-fat (LF) or Mediterranean/low-carbohydrate (MED/LC + 28 g walnuts/day) diets with/without moderate physical activity. HFC and abdominal fat-depots were measured using magnetic resonance imaging at baseline, after 6 (sub-study, n = 158) and 18 months. Results: Of 278 participants (mean HFC 10.2% [range: 0.01%-50.4%]), the retention rate was 86.3%. The %HFC substantially decreased after 6 months (-6.6% absolute units [-41% relatively]) and 18 months (-4.0% absolute units [-29% relatively]; p <0.001 vs. baseline). Reductions of HFC were associated with decreases in VAT beyond weight loss. After controlling for VAT loss, decreased %HFC remained independently associated with reductions in serum gamma glutamyltransferase and alanine aminotransferase, circulating chemerin, and glycated hemoglobin (p <0.05). While the reduction in HFC was similar between physical activity groups, MED/LC induced a greater %HFC decrease (p = 0.036) and greater improvements in cardiometabolic risk parameters (p <0.05) than the LF diet, even after controlling for VAT changes. Yet, the greater improvements in cardiometabolic risk parameters induced by MED/LC were all markedly attenuated when controlling for HFC changes. Conclusions: %HFC is substantially reduced by diet-induced moderate weight loss and is more effectively reduced by the MED/LC diet than the LF diet, independently of VAT changes. The beneficial effects of the MED/LC diet on specific cardiometabolic parameters appear to be mediated more by decreases in %HFC than VAT loss. Lay Summary: High hepatic fat content is associated with metabolic syndrome, type 2 diabetes mellitus, and coronary heart disease. In the CENTRAL 18-month intervention trial, a Mediterranean/low-carbohydrate diet induced a greater decrease in hepatic fat content than a low-fat diet, conferring beneficial health effects that were beyond the favorable effects of visceral fat loss. ClinicalTrials.gov Identifier: NCT01530724.

Effect of a walnut diet on office and 24-hour ambulatory blood pressure in elderly individuals: findings From the WAHA randomized trial.

Domènech, M., M. Serra-Mir, I. Roth, T. Freitas-Simoes, C. Valls-Pedret, M. Cofán, A. López, A. Sala-Vila, C. Calvo, S. Rajaram, J. Sabaté, 2019. Effect of a walnut diet on office and 24-hour ambulatory blood pressure in elderly individuals: findings From the WAHA randomized trial. Hypertension. 73(5):1049-1057.

Nut consumption lowers blood cholesterol and is associated with reduced cardiovascular disease, but effects on blood pressure (BP) are inconsistent. We assessed the 2-year effects of a walnut diet versus a control diet on office BP and 24-hours ambulatory BP in free-living elders participating in the Walnuts and Healthy Aging study, a randomized trial testing the effects of walnuts at ≈15% energy on age-related disorders. In a prespecified analysis, we enrolled 305 participants, of whom 236 (75%) completed the study (65% women; age, 69 years; 60% with mild hypertension). Walnuts were well tolerated, and compliance was >98%. Mean baseline office BP was 128/79 mm Hg. Adjusted changes from baseline in mean office systolic BP were −4.61 mm Hg (95% CI, −7.43 to −1.79 mm Hg) in the walnut group and −0.59 mm Hg (−3.38 to 2.21 mm Hg) in controls (P=0.051). Respective changes in mean systolic 24-hour ambulatory BP were −3.86 mm Hg (CI, −5.45 to −2.26 mm Hg) and −2.00 mm Hg (CI, −3.58 to −0.42 mm Hg; P=0.111). No changes in diastolic BP were observed. In participants in the upper tertile of baseline 24-hour ambulatory systolic BP (>125 mm Hg), mean 2-year systolic 24-hour BP was −8.5 mm Hg (CI, −12 to −5.0 mm Hg) in the walnut group and −2.5 mm Hg (CI,−6.3 to 1.3 mm Hg) in controls (P=0.034). During the trial, participants in the walnut group required less uptitration of antihypertensive medication and had better overall BP regulation than controls. Walnut consumption reduces systolic BP in elderly subjects, particularly in those with mild hypertension.

Metabolic influence of walnut phenolic extract on mitochondria in a colon cancer stem cell model.

Choi, J., P.K. Shin, Y. Kim, C.P. Hong, S.W. Choi, 2019. Metabolic influence of walnut phenolic extract on mitochondria in a colon cancer stem cell model. Eur J Nutr. 58(4):1635-1645.

Purpose: Walnut phenolic extract (WPE) reduces proliferation and enhances differentiation of colon cancer stem cells (CSCs). The present study investigated the metabolic influence of WPE on the mitochondrial function of colon CSCs to determine its underlying mechanism. Methods: CD133+CD44+ HCT116 colon cancer cells were selected by fluorescence-activated cell sorting and were treated with or without 40 µg/mL WPE. RNA-sequencing (RNA-Seq) was performed to identify differentially expressed genes (DEGs), which were further validated with RT-PCR. WPE-induced alterations in mitochondrial function were investigated through a mitochondrial stress test by determining cellular oxygen consumption rate (OCR), an indicator of mitochondrial respiration, and extracellular acidification rate (ECAR), an indicator of glycolysis, which were further confirmed by glucose uptake and lactate production tests. Results: RNA-Seq analysis identified two major functional clusters: metabolic and mitochondrial clusters. WPE treatment shifted the metabolic profile of cells towards the glycolysis pathway (ΔECAR = 36.98 mpH/min/ptn, p = 0.02) and oxidative pathway (ΔOCR = 29.18 pmol/min/ptn, p = 0.00001). Serial mitochondrial stimulations using respiration modulators, oligomycin, carbonyl cyanide-4 (trifluoromethoxy) phenylhydrazone, and rotenone/antimycin A, found an increased potential of mitochondrial respiration (ΔOCR = 111.5 pmol/min/ptn, p = 0.0006). WPE treatment also increased glucose uptake (Δ = 0.39 pmol/µL, p = 0.002) and lactate production (Δ = 0.08 nmol/µL, p = 0.005). Conclusions: WPE treatment shifts the mitochondrial metabolism of colon CSC towards more aerobic glycolysis, which might be associated with the alterations in the characteristics of colon CSC.