Effects of walnut consumption for 2 years on older adults' bone health in the Walnuts and Healthy Aging (WAHA) trial.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Interplay of Walnut Consumption, Changes in Circulating miRNAs and Reduction in LDL-Cholesterol in Elders.

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, n = 164) and a walnut group (WG, 15% of daily energy as walnuts, ~30-60 g/d, n = 166). Participants in the WG showed a 1 year decrease in LDL-C (-9.07, (95% confidence interval: -12.87; -5.73) mg/dL; p = 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.

Reflexión sobre el sentido del sufrimiento en la enfermedad del Alzheimer / Reflexion on the meaning of suffering in alzheimer's disease

En el transcurso de la vida, las personas experimentan diferentes momentos y circunstancias que las conducen al sufrimiento, la mayoría de veces sin encontrarle un sentido lógico y racional. La enfermedad desarrolla en la persona sufrimiento. Un hecho tan evidente y a la vez tan misterioso que provoca en los profesionales sanitarios un desafío terapéutico difícilmente abordable.Es importante señalar que el sufrimiento es una parte muy importante de la propia enfermedad ya que configura el modo de ser de la persona y la manera que tiene ésta de enfrentarse a dicha experiencia desagradable. En el caso de la enfermedad de Alzheimer (EA), la dificultad de hacer frente a este desafío terapéutico se vuelve más intrincado aún al ser una patología neurológica, progresiva e irreversible, comportando, debido a su mal pronóstico y su progresiva evolución, un empeoramiento secuencial de la persona, en la que se ven agravados entre otras, la capacidad de expresión y el uso del lenguaje. El sufrimiento no tratado contribuye a la reducción de la calidad de vida y puede conducir a un aumento de los síntomas conductuales y psicológicos en usuarios con la EA.“¿Por qué?” suele ser la pregunta más repetida en momentos de abatimiento, incertidumbre, desconcierto, enfermedad. Una pregunta de sentido entorno al sufrimiento que busca una respuesta esperanzadora y que encierra tras de sí la grandeza de un misterio específico de cada persona.En este sentido, a través del presente estudio, se busca indagar en el sentido del sufrimiento en pacientes con EA. (AU)

In the course of life, people experience different moments and circumstances that lead to suffering, the vast majority of times without finding a logical and rational meaning. The disease develops in the person suffering. A fact so evident and at the same time so mysterious that it causes healthcare professionals a therapeutic challenge that is difficult to board.It is important to point out that suffering is a very important part of the illness itself, since it configures the way of being of the person and the way he has to face this unpleasant experience. In the case of Alzheimer’s disease, the difficulty of facing this therapeutic challenge becomes even more intricate as it is a progressive and irreversible neurological pathology, leading to, due to its poor prognosis and progressive evolution, a sequential worsening of the person disease, in which the capacity for expression and the use of language are aggravated among others. Suffering did not contribute to the reduction in quality of life and may lead to an increase in behavioral and psychological symptoms in users with Alzheimer’s disease. «Why?» It is usually the most repeated question in moments of dejection, uncertainty, bewilderment, illness. A meaningful question around suffering that searches for a hopeful answer and that holds behind it the greatness of a specific mystery of each person.In this sense, through this study, we seek to investigate the meaning of suffering in patients with Alzheimer’s disease. (AU)

Effects of Supplementing the Usual Diet with a Daily Dose of Walnuts for Two Years on Metabolic Syndrome and Its Components in an Elderly Cohort.

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.

Effect of a 2-year diet intervention with walnuts on cognitive decline. The Walnuts And Healthy Aging (WAHA) study: a randomized controlled trial.

BACKGROUND: Walnut consumption counteracts oxidative stress and inflammation, 2 drivers of cognitive decline. Clinical data concerning effects on cognition are lacking. OBJECTIVES: The Walnuts And Healthy Aging study is a 2-center (Barcelona, Spain; Loma Linda, CA) randomized controlled trial examining the cognitive effects of a 2-y walnut intervention in cognitively healthy elders. METHODS: We randomly allocated 708 free-living elders (63-79 y, 68% women) to a diet enriched with walnuts at ∼15% energy (30-60 g/d) or a control diet (abstention from walnuts). We administered a comprehensive neurocognitive test battery at baseline and 2 y. Change in the global cognition composite was the primary outcome. We performed repeated structural and functional brain MRI in 108 Barcelona participants. RESULTS: A total of 636 participants completed the intervention. Besides differences in nutrient intake, participants from Barcelona smoked more, were less educated, and had lower baseline neuropsychological test scores than those from Loma Linda. Walnuts were well tolerated and compliance was good. Modified intention-to-treat analyses (n = 657) uncovered no between-group differences in the global cognitive composite, with mean changes of -0.072 (95% CI: -0.100, -0.043) in the walnut diet group and -0.086 (95% CI: -0.115, -0.057) in the control diet group (P = 0.491). Post hoc analyses revealed significant differences in the Barcelona cohort, with unadjusted changes of -0.037 (95% CI: -0.077, 0.002) in the walnut group and -0.097 (95% CI: -0.137, -0.057) in controls (P = 0.040). Results of brain fMRI in a subset of Barcelona participants indicated greater functional network recruitment in a working memory task in controls. CONCLUSIONS: Walnut supplementation for 2 y had no effect on cognition in healthy elders. However, brain fMRI and post hoc analyses by site suggest that walnuts might delay cognitive decline in subgroups at higher risk. These encouraging but inconclusive results warrant further investigation, particularly targeting disadvantaged populations, in whom greatest benefit could be expected.This trial was registered at clinicaltrials.gov as NCT01634841.

Consumption of Aged White Wine under a Veil of Flor Reduces Blood Pressure-Increasing Plasma Nitric Oxide in Men at High Cardiovascular Risk.

BACKGROUND: Hypertension remains the largest attributable risk factor of cardiovascular disease (CVD), and a reduction of cardiovascular events is linked to diminished elevated blood pressure (BP) values. High alcohol intake is a common cause of hypertension, but some studies have suggested that moderate wine consumption may reduce BP and increase plasma nitric oxide (NO) due to its polyphenol content. OBJECTIVE: The aim of the present study was to compare the effects of Andalusian aged white wine (AWW) under a veil of flor, an alcoholic beverage with a moderate polyphenol content, with those of gin, an alcoholic beverage without polyphenols, on BP and plasma NO in men at high cardiovascular risk. METHODS: This study was designed as an open, randomized crossover-controlled trial in which 38 high-risk male volunteers, aged 55 to 80, received 30 g of ethanol daily in the form of AWW or gin. This was carried out over the course of three weeks, after a two-week washout period. At baseline and after each intervention period, BP, anthropometric parameters, and plasma NO were measured; food intake was also recorded, and physical activity was monitored. RESULTS: Compared to gin, AWW significantly reduced systolic and diastolic BP (p ≤ 0.033; both) and increased plasma NO levels (p = 0.013). Additionally, changes in BP values observed after AWW significantly correlated with increases in plasma NO. No changes in food intake, physical activity, body weight, or waist were observed between the two intervention periods. CONCLUSIONS: Moderate daily consumption of AWW may be useful to reduce elevated BP due to an increase of NO synthesis. This effect could be attributed to grape-derived compounds in AWW, such as polyphenols, which are not present in gin.

Effect of a Walnut Diet on Office and 24-Hour Ambulatory Blood Pressure in Elderly Individuals.

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. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT01634841 .

The red blood cell proportion of arachidonic acid relates to shorter leukocyte telomeres in Mediterranean elders: A secondary analysis of a randomized controlled trial.

BACKGROUND & AIMS: Shortening of leukocyte telomere length (LTL) is a biomarker of aging. Epidemiologic studies of LTL in relation to dietary fatty acids have reported conflicting results. The red blood cell (RBC) fatty acid status is a valid objective biomarker of long-term dietary intake of C18:2n-6, C18:3n-3 and long-chain n-3 polyunsaturated fatty acids (C20:5n-3 and C22:6n-3). In healthy older individuals, we investigated whether LTL relates to the RBC proportions of the main dietary polyunsaturated fatty acids (PUFA), and to the RBC proportion of arachidonic acid (C20:4n-6), a fatty acid that can generate pro-inflammatory lipid mediators once released from cell membranes. DESIGN: Cross-sectional study in 344 subjects (mean age 68.8 y, 68.6% women) who participated in a randomized controlled trial testing whether a diet enriched in walnuts can delay the onset of age-related diseases (https://clinicaltrials.gov/ct2/show/NCT01634841). At baseline, we assessed LTL by high-throughput quantitative fluorescence and determined fatty acids in RBCs by gas chromatography. RESULTS: In multivariate models adjusted for age and gender, the RBC proportions of dietary PUFA were unrelated to LTL. In contrast, the RBC proportion of arachidonic acid inversely related to LTL (regression coefficient [95% confidence interval], -0.10 (-0.19 to -0.01), P = 0.023). CONCLUSION: An increasing proportion of C20:4n-6 in RBCs is associated with shorter telomeres. Further research is needed to investigate the role of this fatty acid and its derived lipid mediators in the aging process.

Acute consumption of Andalusian aged wine and gin decreases the expression of genes related to atherosclerosis in men with high cardiovascular risk: Randomized intervention trial.

BACKGROUND: Atherosclerosis is an inflammatory disease. Previous studies have suggested the beneficial effects of moderate consumption of alcoholic beverages on reducing cardiovascular risk (CVR). The aim of this study was to evaluate the effects of acute consumption of Andalusian aged wine (AAW) and gin by analyzing the expression of genes related to the appearance and progression of atherosclerosis in men with high CVR. METHODS: We performed an open, randomized, controlled, crossover trial including 41 men with high CVR between 55 and 80 years age, who received a single dose of AAW or gin (0.5 g ethanol/kg). The expression of 10 genes related to atherosclerosis was determined by RT-PCR at baseline and 4 h after the intervention. RESULTS: Gene expression analysis 4 h after consumption of each alcoholic beverage showed a significant decrease in Toll-like receptors 4 and 6 (TLR4, TLR6) and Caspase-1 (p < 0.05 all). Additionally, TLR2, Interleukin-1 receptor, chemokine receptor 3 and inflammasome expression decreased after AAW intake (p < 0.05, all) while only chemokine receptor 5 decreased after gin consumption (p = 0.039). CONCLUSION: The decrease in the expression of several genes related to the appearance and progression of atherosclerosis was greater after AAW than gin intake, suggesting that the phenolic content of AAW may play a protective role against atherosclerosis.

Consumption of aged white wine modulates cardiovascular risk factors via circulating endothelial progenitor cells and inflammatory biomarkers.

BACKGROUND & AIMS: There is compelling evidence showing that moderate alcohol consumption reduces cardiovascular risk factors related to atherosclerosis. The aim of this study was to evaluate the effects of aged white wine (AWW) and gin on circulating endothelial progenitor cells (EPC) and the expression of cell adhesion molecules, inflammatory cytokines and chemokines related to atherosclerosis in high cardiovascular risk subjects. METHODS: This was an open, randomized, controlled, crossover study in 38 high-risk male volunteers between 55 and 80 years of age randomized to receive 30 g of ethanol/day as AWW or gin during 3 weeks. We used the paired two-tailed t-test to compare differences in outcome variables in response to each intervention. Carryover effects for the two periods were evaluated comparing the outcome variables before the AWW and gin interventions. RESULTS: Compared to gin, AWW intake was associated with a significant 39.6% increase in EPCs. Expression of CD31 and CD40 in T-lymphocytes and of CCR2 and CD36 in monocytes also decreased significantly after AWW intake. In addition, compared to gin, AWW was associated with a significant decrease of plasma pro-inflammatory biomarkers interleukin-8 and interleukin-18 and vascular and intercellular adhesion molecules-1. Lfa-1, Mac-1, VLA4, CD40 and CD31 expression in monocytes and interferon gamma (IFN-γ) concentrations significantly decreased after intake of both alcoholic beverages. CONCLUSIONS: AWW shows a greater ability to repair and maintain endothelial integrity compared to gin. This effect is probably due to grape-derived minor components in AWW, which are absent in gin.

Walnut Consumption for Two Years and Leukocyte Telomere Attrition in Mediterranean Elders: Results of a Randomized Controlled Trial.

Randomized controlled trials on diet and shortening of leukocyte telomere length (LTL) mostly focus on marine-derived n-3 polyunsaturated fatty acids (PUFA). Walnuts are a sustainable source of n-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 (n = 80) or control group (n = 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 (p = 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.

Favourable nutrient intake and displacement with long-term walnut supplementation among elderly: results of a randomised trial.

Older adults tend to require fewer energy content and higher levels of nutrients to promote and maintain optimal health. Regrettably, dietary variety and quality are known to decline with advancing age. We conducted a 2-year prospective, randomised, dietary intervention trial where we asked free-living elderly subjects (63-79 years) on self-selected habitual diets to incorporate walnuts daily into their diet (15 % energy). We then compared their nutrient intake with that of a similar group of concurrent participants on self-selected habitual diets but abstaining from walnut consumption (control). No recipes or advice on use of nuts were provided. Dietary intake was assessed by multiple unannounced 24-h telephone dietary recalls. On average, walnut supplement consumption was 43 g/d or 1171·5 kJ (281 kcal). The mean daily energy intake was 954 kJ (228 kcal) higher in the walnut group than in the control group (P<0·001). Compared with control, participants in the walnut group reported significantly higher intake of total protein, vegetable protein, total PUFA and n-3 and n-6 PUFA; and significantly lower intake of total carbohydrate, animal protein, SFA, and Na. An estimated 19 % of total energy and 25 % of total fat from other food sources was displaced. Displacement of MUFA and total PUFA was 21 and 16 %, respectively. Thus adding a daily supplement of walnuts to an ad libitum diet of older adults can induce favourable modifications to the nutrient profile in a way that addresses declining nutrient intake associated with aging.

The Walnuts and Healthy Aging Study (WAHA): Protocol for a Nutritional Intervention Trial with Walnuts on Brain Aging.

Introduction: 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. Methods: 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. Results: 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. Discussion: 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 non-alcoholic fraction of beer increases stromal cell derived factor 1 and the number of circulating endothelial progenitor cells in high cardiovascular risk subjects: a randomized clinical trial.

RATIONALE: Moderate alcohol consumption is associated with a decrease in cardiovascular risk, but fermented beverages seem to confer greater cardiovascular protection due to their polyphenolic content. Circulating endothelial progenitor cells (EPC) are bone-marrow-derived stem cells with the ability to repair and maintain endothelial integrity and function and are considered as a surrogate marker of vascular function and cumulative cardiovascular risk. Nevertheless, no study has been carried out on the effects of moderate beer consumption on the number of circulating EPC in high cardiovascular risk patients. OBJECTIVE: To compare the effects of moderate consumption of beer, non-alcoholic beer and gin on the number of circulating EPC and EPC-mobilizing factors. METHODS: In this crossover trial, 33 men at high cardiovascular risk were randomized to receive beer (30 g alcohol/d), the equivalent amount of polyphenols in the form of non-alcoholic beer, or gin (30 g alcohol/d) for 4 weeks. Diet and physical exercise were carefully monitored. RESULTS: The number of circulating EPC and EPC-mobilizing factors were determined at baseline and after each intervention. After the beer and non-alcoholic beer interventions, the number of circulating EPC significantly increased by 8 and 5 units, respectively, while no significant differences were observed after the gin period. In correlation, stromal cell derived factor 1 increased significantly after the non-alcoholic and the beer interventions. CONCLUSIONS: The non-alcoholic fraction of beer increases the number of circulating EPC in peripheral blood from high cardiovascular risk subjects. CLINICAL TRIAL REGISTRATION: http://www.controlled-trials.com/ISRCTN95345245 ISRCTN95345245.