Aims
The aim of this study was to evaluate the effect of the Mediterranean diet (MedDiet) on the incidence of heart failure (HF), a pre‐specified secondary outcome in the PREDIMED (PREvención con ...DIeta MEDiterránea) primary nutrition‐intervention prevention trial.
Methods and results
Participants at high risk of cardiovascular disease were randomly assigned to one of three diets: MedDiet supplemented with extra‐virgin olive oil (EVOO), MedDiet supplemented with nuts, or a low‐fat control diet. Incident HF was ascertained by a Committee for Adjudication of events blinded to group allocation. Among 7403 participants without prevalent HF followed for a median of 4.8 years, we observed 29 new HF cases in the MedDiet with EVOO group, 33 in the MedDiet with nuts group, and 32 in the control group. No significant association with HF incidence was found for the MedDiet with EVOO and MedDiet with nuts, compared with the control group hazard ratio (HR) 0.68; 95% confidence interval (CI) 0.41–1.13, and HR 0.92; 95% CI 0.56–1.49, respectively.
Conclusion
In this sample of adults at high cardiovascular risk, the MedDiet did not result in lower HF incidence. However, this pre‐specified secondary analysis may have been underpowered to provide valid conclusions. Further randomized controlled trials with HF as a primary outcome are needed to better assess the effect of the MedDiet on HF risk.
Trial registration: ISRCTN35739639.
Nutritional strategies to maintain bone health in aging individuals are of great interest. Given the beneficial nutrient composition of walnuts, rich in alpha-linolenic (the vegetable n-3 fatty acid) ...and polyphenols, their regular consumption might be a dietary option to reduce age-related bone loss. We determined whether daily walnut consumption improves bone mineral density (BMD) and circulating biomarkers of bone turnover.
The Walnuts and Healthy Aging study (WAHA) is a two-center, parallel, randomized controlled trial evaluating the effect of a diet enriched with walnuts at ≈15% energy compared with a control diet for 2 years on age-related health outcomes in healthy men and women aged 63-79 years. Changes in BMD were a prespecified secondary outcome only at the Barcelona node of the trial, where 352 participants were randomized. Retention rate was 92.6%. Primary endpoints were 2-year changes in BMD at the spine and the nondominant femoral neck, determined by dual-energy X-ray absorptiometry (DXA). Secondary endpoints were 2-year changes in bone turnover biomarkers (adrenocorticotropic hormone, Dickkopf WNT signaling pathway inhibitor-1, osteoprotegerin, osteocalcin, osteopontin, sclerostin, parathyroid hormone, and fibroblast growth factor-23), which were quantified in 211 randomly selected participants.
The walnut diet versus the control diet had no effect on 2-year changes in BMD at the spine (0.15% vs. 0.35%, p = 0.632) and femoral neck (-0.90% vs. -0.70%, p = 0.653), or on bone turnover biomarkers. Results were similar in participants treated or not with bone resorption inhibitors or those with or without osteoporosis/osteopenia at inclusion.
Compared with the usual diet, a diet enriched with walnuts at 15% of energy for 2 years failed to improve BMD or circulating markers of bone metabolism in healthy older people.
: To assess the effects of chronic walnut consumption on body weight and adiposity in elderly individuals.
: The Walnuts and Healthy Aging study is a dual-center (Barcelona, Spain and Loma Linda ...University (LLU)), 2-year randomized parallel trial. This report concerns only the LLU cohort. Healthy elders (mean age 69 year, 67% women) were randomly assigned to walnut (
= 183) or control diets (
= 173). Subjects in the walnut group received packaged walnuts (28⁻56 g/day), equivalent to ≈15% of daily energy requirements, to incorporate into their habitual diet, while those in the control group abstained from walnuts. Adiposity was measured periodically, and data were adjusted for in-trial changes in self-reported physical activity.
: After 2 years, body weight significantly decreased (
0.031), while body fat significantly increased (
0.0001). However, no significant differences were observed between the control and walnut groups regarding body weight (-0.6 kg and -0.4 kg, respectively,
0.67) or body fat (+0.9% and +1.3%, respectively,
0.53). Lean body mass, waist circumference, and waist-to-hip ratio remained essentially unchanged. Sensitivity analyses were consistent with the findings of primary analysis.
: Our findings indicate that walnuts can be incorporated into the daily diet of healthy elders without concern for adverse effects on body weight or body composition.
Purpose
Epidemiological studies and clinical trials support the association of nut consumption with a lower risk of prevalent non-communicable diseases, particularly cardiovascular disease. However, ...the molecular mechanisms underlying nut benefits remain to be fully described. MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression and play a pivotal role in health and disease. Exosomes are extracellular vesicles released from cells and mediate intercellular communication. Whether nut consumption modulates circulating miRNAs (c-miRNAs) transported in exosomes is poorly described.
Methods
Cognitively healthy elderly subjects were randomized to either control (
n
= 110, abstaining from walnuts) or daily supplementation with walnuts (15% of their total energy, ≈30–60 g/day,
n
= 101) for 1-year. C-miRNAs were screened in exosomes isolated from 10 samples, before and after supplementation, and identified c-miRNA candidates were validated in the whole cohort. In addition, nanoparticle tracking analysis and lipidomics were assessed in pooled exosomes from the whole cohort.
Results
Exosomal hsa-miR-32-5p and hsa-miR-29b-3p were consistently induced by walnut consumption. No major changes in exosomal lipids, nanoparticle concentration or size were found.
Conclusion
Our results provide novel evidence that certain c-miRNAs transported in exosomes are modulated by walnut consumption. The extent to which this finding contributes to the benefits of walnuts deserves further research.
Accumulating evidence links nut consumption with an improved risk of metabolic syndrome (MetS); however, long-term trials are lacking. We examined the effects of a daily dose of walnuts for two years ...on MetS in a large elderly cohort. A total of 698 healthy elderly participants were randomly assigned to either a walnut supplemented or a control diet. The participants in the walnut group were provided with packaged walnuts (1, 1.5, or 2 oz. or ~15% of energy) and asked to incorporate them into their daily habitual diet. The participants in the control group were asked to continue with their habitual diet and abstain from eating walnuts and other tree nuts. Intake of n-3 fatty acid supplements was not permitted in either group. Fasting blood chemistries, blood pressure, and anthropometric measurements were obtained at baseline and at the end of intervention. A total of 625 participants (67% women, mean age 69.1 y) completed this two-year study (90% retention rate). Triglycerides decreased in both walnut (-0.94 mg/dl) and control (-0.96 mg/dl) groups, with no significant between-group differences. There was a non-significant decrease in systolic and diastolic blood pressure in the walnut group (-1.30 and -0.71 mm Hg, respectively) and no change in the control group. Fasting blood glucose decreased by ~1 point in both the walnut and control groups. There were no significant between-group differences in the development or reversion of MetS. In conclusion, supplementing the diet of older adults with a daily dose of walnuts had no effect on MetS status or any of its components, although the walnut group tended to have lower blood pressure.
An unwanted consequence of population aging is the growing number of elderly at risk of neurodegenerative disorders, including dementia and macular degeneration. As nutritional and behavioral changes ...can delay disease progression, we designed the Walnuts and Healthy Aging (WAHA) study, a two-center, randomized, 2-year clinical trial conducted in free-living, cognitively healthy elderly men and women. Our interest in exploring the role of walnuts in maintaining cognitive and retinal health is based on extensive evidence supporting their cardio-protective and vascular health effects, which are linked to bioactive components, such as n-3 fatty acids and polyphenols.
The primary aim of WAHA is to examine the effects of ingesting walnuts daily for 2 years on cognitive function and retinal health, assessed with a battery of neuropsychological tests and optical coherence tomography, respectively. All participants followed their habitual diet, adding walnuts at 15% of energy (≈30-60 g/day) (walnut group) or abstaining from walnuts (control group). Secondary outcomes include changes in adiposity, blood pressure, and serum and urinary biomarkers in all participants and brain magnetic resonance imaging in a subset.
From May 2012 to May 2014, 708 participants (mean age 69 years, 68% women) were randomized. The study ended in May 2016 with a 90% retention rate.
The results of WAHA might provide high-level evidence of the benefit of regular walnut consumption in delaying the onset of age-related cognitive impairment and retinal pathology. The findings should translate into public health policy and sound recommendations to the general population (ClinicalTrials.gov identifier NCT01634841).
The mechanisms underlying the lipid-lowering effect of nuts remain elusive. This study explores whether one-year supplementation with walnuts decreases LDL-cholesterol (LDL-C) by affecting the ...expression of circulating microRNAs (c-miRNA). In this sub-study of the Walnuts and Healthy Aging (WAHA) trial, we obtained fasting serum at baseline and at 1 year from 330 free-living participants (63-79 year, 68% women), allocated into a control group (CG, abstinence from walnuts,
= 164) and a walnut group (WG, 15% of daily energy as walnuts, ~30-60 g/d,
= 166). Participants in the WG showed a 1 year decrease in LDL-C (-9.07, (95% confidence interval: -12.87; -5.73) mg/dL;
= 0.010 versus changes in the CG). We conducted a miRNA array in eight randomly selected participants in the WG who decreased in LDL-C. This yielded 53 c-miRNAs with statistically significant changes, 27 of which survived the correction for multiple testing. When validating them in the full population, statistical significance lasted for hsa-miR-551a, being upregulated in the WG. In mediation analysis, the change in hsa-miR-551a was unrelated to LDL-C decrease. Long-term supplementation with walnuts decreased LDL-C independently of the changes in c-miRNA. The hsa-miR-551a upregulation, which has been linked to a reduced cell migration and invasion in several carcinomas, suggests a novel mechanism of walnuts in cancer risk.
Randomized controlled trials on diet and shortening of leukocyte telomere length (LTL) mostly focus on marine-derived
-3 polyunsaturated fatty acids (PUFA). Walnuts are a sustainable source of
-3 ...PUFA. We investigated whether inclusion of walnuts (15% of energy) in the diet for 2 years would maintain LTL in cognitively healthy elders (63⁻79 years old) compared to a control group (habitual diet, abstaining from walnuts). This opportunistic sub-study was conducted within the Walnuts and Healthy Aging study, a dual-centre (Barcelona, Spain and Loma Linda University, California) parallel trial. A sub-set of the Barcelona site participants were randomly assigned to the walnut (
= 80) or control group (
= 69). We assessed LTL at baseline and at 2 years and we conducted repeated-measures ANCOVA with 2 factors: time (baseline, 2 years) and group (control, walnut) and their interaction. Adjusted means (95% confidence interval) of LTL (in kb) in controls were 7.360 (7.084,7.636) at baseline and 7.061 (6.835,7.288) after 2 years; corresponding values in the walnut group were 7.064 (6.807,7.320) and 7.074 (6.864,7.284). The time × intervention interaction was nearly significant (
= 0.079), suggestive of a trend of walnut consumption in preserving LTL. This exploratory research finding should be confirmed in trials with adequate statistical power.
IMPORTANCE: Oxidative stress and vascular impairment are believed to partly mediate age-related cognitive decline, a strong risk factor for development of dementia. Epidemiologic studies suggest that ...a Mediterranean diet, an antioxidant-rich cardioprotective dietary pattern, delays cognitive decline, but clinical trial evidence is lacking. OBJECTIVE: To investigate whether a Mediterranean diet supplemented with antioxidant-rich foods influences cognitive function compared with a control diet. DESIGN, SETTING, AND PARTICIPANTS: Parallel-group randomized clinical trial of 447 cognitively healthy volunteers from Barcelona, Spain (233 women 52.1%; mean age, 66.9 years), at high cardiovascular risk were enrolled into the Prevención con Dieta Mediterránea nutrition intervention trial from October 1, 2003, through December 31, 2009. All patients underwent neuropsychological assessment at inclusion and were offered retesting at the end of the study. INTERVENTIONS: Participants were randomly assigned to a Mediterranean diet supplemented with extravirgin olive oil (1 L/wk), a Mediterranean diet supplemented with mixed nuts (30 g/d), or a control diet (advice to reduce dietary fat). MAIN OUTCOMES AND MEASURES: Rates of cognitive change over time based on a neuropsychological test battery: Mini-Mental State Examination, Rey Auditory Verbal Learning Test (RAVLT), Animals Semantic Fluency, Digit Span subtest from the Wechsler Adult Intelligence Scale, Verbal Paired Associates from the Wechsler Memory Scale, and the Color Trail Test. We used mean z scores of change in each test to construct 3 cognitive composites: memory, frontal (attention and executive function), and global. RESULTS: Follow-up cognitive tests were available in 334 participants after intervention (median, 4.1 years). In multivariate analyses adjusted for confounders, no between-group differences were observed for cognitive tests. Similarly adjusted cognitive composites (mean z scores with 95% CIs) for changes above baseline of the memory composite were 0.04 (−0.10 to 0.17) for the Mediterranean diet plus olive oil, 0.10 (−0.04 to 0.24; P = .04 vs controls) for the Mediterranean diet plus nuts, and −0.16 (−0.32 to −0.01) for the control diet. Respective changes from baseline of the frontal cognition composite were 0.23 (0.02 to 0.43; P = .004 vs controls), 0.03 (−0.26 to 0.32), and −0.33 (−0.57 to −0.09). Changes from baseline of the global cognition composite were 0.04 (−0.12 to 0.20; P = .008 vs controls) for the Mediterranean diet plus olive oil, −0.04 (−0.27 to 0.19) for the Mediterranean diet plus nuts, and −0.37 (−0.56 to −0.17) for the control diet. All cognitive composites significantly (P < .05) decreased from baseline in controls. CONCLUSIONS AND RELEVANCE: In an older population, a Mediterranean diet supplemented with olive oil or nuts was associated with improved composite measures of cognitive function. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN35739639
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