Association between cholesterol efflux capacity and peripheral artery disease in coronary heart disease patients with and without type 2 diabetes: from the CORDIOPREV study.

BACKGROUND: Peripheral artery disease (PAD) is recognized as a significant predictor of mortality and adverse cardiovascular outcomes in patients with coronary heart disease (CHD). In fact, coexisting PAD and CHD is strongly associated with a greater coronary event recurrence compared with either one of them alone. High-density lipoprotein (HDL)-mediated cholesterol efflux capacity (CEC) is found to be inversely associated with an increased risk of incident CHD. However, this association is not established in patients with PAD in the context of secondary prevention. In this sense, our main aim was to evaluate the association between CEC and PAD in patients with CHD and whether the concurrent presence of PAD and T2DM influences this association. METHODS: CHD patients (n = 1002) from the CORDIOPREV study were classified according to the presence or absence of PAD (ankle-brachial index, ABI ≤ 0.9 and ABI > 0.9 and < 1.4, respectively) and T2DM status. CEC was quantified by incubation of cholesterol-loaded THP-1 cells with the participants' apoB-depleted plasma was performed. RESULTS: The presence of PAD determined low CEC in non-T2DM and newly-diagnosed T2DM patients. Coexisting PAD and newly-diagnosed T2DM provided and additive effect providing an impaired CEC compared to non-T2DM patients with PAD. In established T2DM patients, the presence of PAD did not determine differences in CEC, compared to those without PAD, which may be restored by glucose-lowering treatment. CONCLUSIONS: Our findings suggest an inverse relationship between CEC and PAD in CHD patients. These results support the importance of identifying underlying mechanisms of PAD, in the context of secondary prevention, that provide potential therapeutic targets, that is the case of CEC, and establishing strategies to prevent or reduce the high risk of cardiovascular events of these patients. Trial registration https://clinicaltrials.gov/ct2/show/NCT00924937 . Unique Identifier: NCT00924937.

Trimethylamine n-Oxide (TMAO) Modulates the Expression of Cardiovascular Disease-Related microRNAs and Their Targets.

Diet is a well-known risk factor of cardiovascular diseases (CVDs). Some microRNAs (miRNAs) have been described to regulate molecular pathways related to CVDs. Diet can modulate miRNAs and their target genes. Choline, betaine, and l-carnitine, nutrients found in animal products, are metabolized into trimethylamine n-oxide (TMAO), which has been associated with CVD risk. The aim of this study was to investigate TMAO regulation of CVD-related miRNAs and their target genes in cellular models of liver and macrophages. We treated HEPG-2, THP-1, mouse liver organoids, and primary human macrophages with 6 µM TMAO at different timepoints (4, 8, and 24 h for HEPG-2 and mouse liver organoids, 12 and 24 h for THP-1, and 12 h for primary human macrophages) and analyzed the expression of a selected panel of CVD-related miRNAs and their target genes and proteins by real-time PCR and Western blot, respectively. HEPG-2 cells were transfected with anti-miR-30c and syn-miR-30c. TMAO increased the expression of miR-21-5p and miR-30c-5p. PER2, a target gene of both, decreased its expression with TMAO in HEPG-2 and mice liver organoids but increased its mRNA expression with syn-miR-30c. We concluded that TMAO modulates the expression of miRNAs related to CVDs, and that such modulation affects their target genes.

The insulin resistance phenotype (muscle or liver) interacts with the type of diet to determine changes in disposition index after 2 years of intervention: the CORDIOPREV-DIAB randomised clinical trial.

AIMS/HYPOTHESIS: The aim of the study was to determine whether basal insulin resistance (IR) phenotype (muscle and/or liver) determines the effect of long-term consumption of a Mediterranean diet or a low-fat diet on tissue-specific IR and beta cell function. METHODS: The study was performed in 642 patients included in The effect of an olive oil rich Mediterranean diet on type 2 diabetes mellitus risk and incidence study (CORDIOPREV-DIAB). A total of 327 patients were randomised to a Mediterranean diet (35% fat; 22% from monounsaturated fatty acids) and 315 to a low-fat diet (<28% fat). At baseline, the patients were classified into four phenotypes according to the type of IR: (1) no IR; (2) muscle IR; (3) liver IR; (4) muscle + liver IR. The hepatic insulin resistance index (HIRI), muscular insulin sensitivity index (MISI) and disposition index were analysed at baseline and after 2 years of follow-up. RESULTS: At baseline, 322 patients presented no IR, 106 presented muscle IR, 109 presented liver IR, and 105 presented muscle + liver IR. With both dietary interventions, HIRI decreased in all patients (p < 0.001) and MISI increased in muscle IR and muscle + liver IR patients (p < 0.01). Long-term intake of the Mediterranean diet increased the disposition index and insulinogenic index in the muscle IR patients (p = 0.042 and p = 0.044, respectively) and the disposition index in the muscle + liver IR patients (p = 0.048), whereas the low-fat diet increased the disposition index in the liver IR patients (p = 0.017). CONCLUSIONS/INTERPRETATION: Although both diets improve insulin sensitivity, there are differences based on basal IR phenotypes. Moreover, according to insulinogenic and disposition index data, a low-fat diet might be more beneficial to patients with liver IR, whereas patients with muscle IR and muscle + liver IR might benefit more from a Mediterranean diet. Trial registration ClinicalTrials.gov NCT00924937 FUNDING: The study was supported by the Ministerio de Economia y Competitividad (AGL2012/39615) and by the Ministerio de Ciencia e Innovacion (PIE14/00005 and PI13/00023).

Genetic contribution to iron status: SNPs related to iron deficiency anaemia and fine mapping of CACNA2D3 calcium channel subunit.

Numerous studies associate genetic markers with iron- and erythrocyte-related parameters, but few relate them to iron-clinical phenotypes. Novel SNP rs1375515, located in a subunit of the calcium channel gene CACNA2D3, is associated with a higher risk of anaemia. The aim of this study is to further investigate the association of this SNP with iron-related parameters and iron-clinical phenotypes, and to explore the potential role of calcium channel subunit region in iron regulation. Furthermore, we aim to replicate the association of other SNPs reported previously in our population. We tested 45 SNPs selected via systematic review and fine mapping of CACNA2D3 region, with haematological and biochemical traits in 358 women of reproductive age. Multivariate analyses include back-step logistic regression and decision trees. The results replicate the association of SNPs with iron-related traits, and also confirm the protective effect of both A allele of rs1800562 (HFE) and G allele of rs4895441 (HBS1L-MYB). The risk of developing anaemia is increased in reproductive age women carriers of A allele of rs1868505 (CACNA2D3) and/or T allele of rs13194491 (HIST1H2BJ). Association of SNPs from fine mapping with ferritin and serum iron suggests that calcium channels could be a potential pathway for iron uptake in physiological conditions.

Low iron status as a factor of increased bone resorption and effects of an iron and vitamin D-fortified skimmed milk on bone remodelling in young Spanish women.

PURPOSE: This study aimed to determine whether there is a relationship between iron status and bone metabolism, and to compare the effects of the consumption, as part of the usual diet, of an iron or iron and vitamin D-fortified skimmed milk on bone remodelling in iron-deficient women. METHODS: Young healthy iron-deficient or iron-sufficient women (serum ferritin ≤30 ng/mL or >30 ng/mL, respectively) were recruited. Iron-deficient women were assigned to a nutritional intervention consisting of a randomised, controlled, double-blind, parallel design trial of 16 weeks during winter. They consumed, as part of their usual diet, an iron (Fe group, n = 54) or iron and vitamin D-fortified (Fe+D group, n = 55) flavoured skimmed milk (iron, 15 mg/day; vitamin D3, 5 µg/day, 200 IU). The iron-sufficient women followed their usual diet without supplementation (R group, n = 56). Dietary intake, body weight, iron biomarkers, 25-hydroxyvitamin D (25OHD), parathyroid hormone (PTH), procollagen-type 1 N-terminal propeptide (P1NP), and aminoterminal telopeptide of collagen I (NTx) were determined. RESULTS: Negative correlations were found between baseline log-ferritin and log-NTx (p < 0.001), and between transferrin and P1NP (p = 0.002). Serum 25OHD increased (from 62 ± 21 to 71 ± 21 nmol/L, mean ± SD, p < 0.001) while P1NP and NTx decreased in Fe+D during the assay (p = 0.004 and p < 0.001, respectively). NTx was lower in Fe+D compared to Fe at week 8 (p < 0.05) and was higher in Fe and Fe+D compared to R throughout the assay (p < 0.01). PTH did not show changes. CONCLUSIONS: Iron deficiency is related with higher bone resorption in young women. Consumption of a dairy product that supplies 5 µg/day of vitamin D3 reduces bone turnover and increases circulating 25OHD to nearly reach an optimal vitamin D status, defined as 25OHD over 75 nmol/L.

A simple and feasible questionnaire to estimate menstrual blood loss: relationship with hematological and gynecological parameters in young women.

BACKGROUND: Menstrual blood loss (MBL) has been shown to be an important determinant in iron status, work performance and well-being. Several methods have been developed to estimate MBL, the standard quantitative method however has limited application in clinical practice as it is expensive and requires women to collect, store and submit their sanitary products for analysis. We therefore aimed to develop a MBL-score based on a questionnaire, and to validate it by several hematological and biochemical parameters in women of childbearing age. METHODS: A total of 165 healthy young women were recruited. Hematological (hematocrit, hemoglobin, erythrocyte, leucocyte and platelet counts) and iron status (serum iron, serum ferritin, serum transferrin, and total iron binding capacity) parameters were analyzed at baseline. Women were asked to fulfill two gynecological questionnaires: a general questionnaire, to inform about the volunteer's general menstrual characteristics; and a MBL questionnaire, to provide details of the duration of menstruation, number of heavy blood loss days, and number and type of pads and/or tampons used during the heaviest bleeding day, for all consecutive menstrual periods during 16 weeks. A MBL-score was calculated for each period and women, and its reliability determined by the Cronbach's alpha coefficient. Pearson's linear correlation tests were performed between blood parameters and the MBL-score. Two clusters were formed according the MBL-score (cluster 1: low MBL and cluster 2: high MBL). RESULTS: Significant higher MBL-score was observed in women who reported having a history of anemia (p = 0.015), staining the bed at night during menstruation (p < 0.001) and suffering inter-menstrual blood loss (p = 0.044), compared to those who did not. Women who used hormonal contraceptives presented lower MBL-scores than the others (p = 0.004). The MBL-score was negatively associated with log-ferritin (p = 0.006) and platelet count (p = 0.011). Women in cluster 1 presented higher ferritin (p = 0.043) than women in cluster 2. CONCLUSIONS: We developed an easy and practical method for estimating menstrual blood loss based on a score calculated from a questionnaire in healthy women at childbearing age. The MBL-score is highly reliable and reflects menstrual blood loss validated by hematological and biochemical parameters.

Influence of diet, menstruation and genetic factors on iron status: a cross-sectional study in Spanish women of childbearing age.

The aim of this study was to investigate the combined influence of diet, menstruation and genetic factors on iron status in Spanish menstruating women (n = 142). Dietary intake was assessed by a 72-h detailed dietary report and menstrual blood loss by a questionnaire, to determine a Menstrual Blood Loss Coefficient (MBLC). Five selected SNPs were genotyped: rs3811647, rs1799852 (Tf gene); rs1375515 (CACNA2D3 gene); and rs1800562 and rs1799945 (HFE gene, mutations C282Y and H63D, respectively). Iron biomarkers were determined and cluster analysis was performed. Differences among clusters in dietary intake, menstrual blood loss parameters and genotype frequencies distribution were studied. A categorical regression was performed to identify factors associated with cluster belonging. Three clusters were identified: women with poor iron status close to developing iron deficiency anemia (Cluster 1, n = 26); women with mild iron deficiency (Cluster 2, n = 59) and women with normal iron status (Cluster 3, n = 57). Three independent factors, red meat consumption, MBLC and mutation C282Y, were included in the model that better explained cluster belonging (R2 = 0.142, p < 0.001). In conclusion, the combination of high red meat consumption, low menstrual blood loss and the HFE C282Y mutation may protect from iron deficiency in women of childbearing age. These findings could be useful to implement adequate strategies to prevent iron deficiency anemia.

Effects of an iron or iron and vitamin D-fortified flavored skim milk on iron metabolism: a randomized controlled double-blind trial in iron-deficient women.

OBJECTIVES: Iron deficiency anemia and vitamin D deficiency are considered global pandemics. The aim of this study was to determine whether the consumption of a dairy product fortified with iron and vitamin D, compared to the equivalent with only added iron, exerts an additional effect on iron metabolism in iron-deficient menstruating women. METHODS: The design was a randomized, placebo-controlled, double-blind, parallel-group trial of 16 weeks' duration. Subjects were randomized into 2 groups that consumed, as part of their usual diet, 500 mL/day of an iron (n = 54) or iron- and vitamin D-fortified (n = 55) flavored skim milk. At baseline and monthly, dietary intake, body weight, and hematological and iron metabolism biomarkers were determined. Serum 25-hydroxyvitamin D was analyzed at baseline and weeks 8 and 16. Data were analyzed by analysis of variance (ANOVA) of repeated measures for time and Time × Group interaction effects. RESULTS: A total of 109 volunteers completed the study. Calcium and iron intakes increased during the intervention (p < 0.001 for both groups). Serum 25-hydroxyvitamin D significantly increased in Fe + D group during the assay (p < 0.001) and at week 16 it was higher compared to the Fe group (p < 0.05). Serum ferritin, serum transferrin, mean corpuscular volume, mean corpuscular hemoglobin, and red blood cell distribution width showed significant time effects but no Time × Group interaction. Higher values of erythrocytes (p = 0.01), hematocrit (p = 0.05), and hemoglobin (p = 0.03) at week 8 were observed in the Fe + D group compared to the Fe group. CONCLUSION: Iron-fortified flavored skim milk does not improve iron status in iron-deficient menstruating women. However, vitamin D fortification slightly enhances erythropoiesis and iron status.

Relationship between vitamin D deficiency, bone remodelling and iron status in iron-deficient young women consuming an iron-fortified food.

BACKGROUND: Iron and vitamin D deficiencies are two of the most widespread nutritional disorders in the world. Our aim was to know whether the consumption of an iron-fortified fruit juice modifies bone remodelling and the possible influence of baseline vitamin D status on the recovery of iron status in a group of iron-deficient women. METHODS: Iron biomarkers, 25-hydroxyvitamin D levels and dietary intake were measured in 123 iron-deficient menstruating women. A subgroup (n = 41) participated in a randomised double-blind placebo-controlled study of 16-weeks during winter. They consumed a placebo fruit juice (P) or iron-fortified fruit juice (F). Dietary intake, 25-hydroxyvitamin D, parathormone (PTH), bone alkaline phosphatase (ALP), aminoterminal telopeptide of collagen I (NTX) and iron biomarkers were determined. RESULTS: Ninety-two per cent of the iron-deficient women were vitamin D deficient or insufficient. Transferrin saturation and 25-hydroxyvitamin D were positively correlated. Iron status improved in F, 25-hydroxyvitamin D decreased in F and P, and PTH, ALP and NTX levels were within the normal range and did not vary. Women with 25-hydroxyvitamin D ≥ 50 nmol/L compared with 25-hydroxyvitamin D < 50 nmol/L showed a higher increase in transferrin saturation (a marker of iron supply to tissues) during iron recovery. CONCLUSION: The prevalence of vitamin D deficiency or insufficiency is very high in iron-deficient women. The recovery of iron status by consuming an iron-fortified food does not affect 25-hydroxyvitamin D levels; however, the increase in iron supply to tissues is lower if the women also present vitamin D deficiency. Although bone health does not seem to be affected in this group of women, correction of iron and vitamin D deficiencies should be promoted in young women to improve present and future health.

A sodium-bicarbonated mineral water reduces gallbladder emptying and postprandial lipaemia: a randomised four-way crossover study.

BACKGROUND: Sodium-bicarbonated mineral waters are reported to have beneficial digestive and hypocholesterolaemic properties. The aim of the study was to investigate the effects of consumption of a sodium-bicarbonated mineral water (BW) with or without a meal, compared to a low mineral content water as the control water (CW), on postprandial serum triacylglycerols (TAG), cholecystokinin (CCK) and gallbladder volume. METHODS: The study design was a four-way randomised controlled crossover trial. Healthy adult men and women (>18 and <40 years, TAG <2.82 mmol/L) consumed 0.5 L of CW + standard meal; 0.5 L of BW + standard meal; and 0.5 L of CW without meal or 0.5 L of BW without meal. RESULTS: BW consumed without meal had no significant effect on the study parameters compared to CW. However, BW with meal induced a lower concentration of serum TAG at 30 min (p = 0.01) and 60 min (p = 0.03) postprandial times, lower CCK concentrations at 30 min (p = 0.002), and higher gallbladder volume at 30 min (p = 0.03), 60 min (p = 0.01) and 120 min (p = 0.04). Gallbladder ejection fraction was lower with the BW (p = 0.03), whilst area under the curve and peak contraction amplitude (lowest gallbladder volume) were higher (p = 0.01, p = 0.02, respectively) compared to the CW. CONCLUSION: Consumption of BW with a meal induces lower levels of CCK and reduces gallbladder emptying and postprandial TAG levels. It is proposed that this sodium-bicarbonated mineral water could be used as part of the habitual diet by the general population in order to reduce cardiovascular risk.

Beneficial Effects of Limosilactobacillus fermentum CECT 5716 Administration to Infants Delivered by Cesarean Section.

Cesarean section (CS) disrupts the natural microbiota colonization process in infants, which might compromise immune system maturation, leading to a higher risk of infections. We evaluated the effect of the probiotic Limosilactobacillus (L.) fermentum CECT 5716 on the incidence of gastrointestinal and respiratory infections in the CS infant subgroups (n = 173) of three randomized clinical trials in which this probiotic strain was demonstrated to be safe and effective for preventing infections. Therefore, the data for the CS infants were extracted to obtain the incidence rate ratio (IRR) and 95% CI for gastrointestinal and respiratory infections for each study and were then combined to obtain a pooled IRR and 95% CI using the generic inverse variance method. There was a significant reduction of 73% in the incidence of gastrointestinal infections in CS infants receiving L. fermentum CECT 5716 compared with those receiving the control formula [n = 173, IRR: 0.27 (0.13, 0.53), p = 0.0002]. Regarding respiratory infections, although pooled results showed a reduction of 14% in the probiotic group, the difference was not statistically significant [n = 173, IRR (95% CI): 0.86 (0.67, 1.11), p = 0.25]. In conclusion, the administration of L. fermentum CECT 5716 to CS-born infants protects them from gastrointestinal infections by reducing the risk by up to 73% in this population.

Evaluation of the effect of Loigolactobacillus coryniformis K8 CECT 5711 consumption in health care workers exposed to COVID-19.

Following the spread of the SARS-CoV-2 coronavirus, an unprecedented burden has been placed on health care systems, with health care workers (HCWs) being most at risk of COVID-19 infection. The effect of the probiotic Loigolactobacillus coryniformis K8 CECT 5711 on frontline HCWs exposed to the virus was studied in a randomized, double-blind, placebo controlled trial. Parameters related to the incidence and severity of COVID-19 as well as the immune response and the side effects of the COVID-19 vaccine were evaluated. For 2 months, a group of 250 front-line HCWs over the age of 20 was randomly allocated to receive either L. coryniformis K8 or a placebo daily. SARS-CoV-2 infection incidence was verified via PCR or antigen test. In those volunteers who were vaccinated during the intervention, serum levels of specific IgG were analyzed at the end of the study. The incidence of COVID-19 infection was very low [IR (SD) = 0.016 (0.011)], and no significant difference was found between the groups [IRR (95% CI): 1.008 (0.140-7.268), p = 0.994]. For immune response analysis, the total sample was divided according to the days between the first dose and the antibody analysis (cutoff points were set at ≤ 56, 57-80 and ≥ 81 days). The specific IgG level decreased over time (p > 0.001). However, in the subgroup of subjects for whom more than 81 days had passed since they received the first dose, the specific IgG levels were significantly higher in the those that took the L. coryniformis K8 [7.12 (0.21)] than in the control group [6.48 (0.19)] (P = 0.040). Interestingly, the subjects who started probiotic consumption before the first dose reported significantly fewer side effects (of any kind) at the 1st dose of the vaccine (OR: 0.524, p = 0.043), specifically less arm pain (OR: 0.467, p = 0.017). In conclusion, the administration of L. coryniformis K8 CECT 5711 to HCWs helps to extend the immune protection generated by the COVID-19 vaccine over time.

Effects of Loigolactobacillus coryniformis K8 CECT 5711 on the Immune Response of Elderly Subjects to COVID-19 Vaccination: A Randomized Controlled Trial.

Elderly people are particularly vulnerable to COVID-19, with a high risk of developing severe disease and a reduced immune response to the COVID-19 vaccine. A randomized, placebo-controlled, double-blind trial to assess the effect of the consumption of the probiotic Loigolactobacillus coryniformis K8 CECT 5711 on the immune response generated by the COVID-19 vaccine in an elderly population was performed. Two hundred nursing home residents >60 yrs that had not COVID-19 were randomized to receive L. coryniformis K8 or a placebo daily for 3 months. All volunteers received a complete vaccination schedule of a mRNA vaccine, starting the intervention ten days after the first dose. Specific IgG and IgA antibody levels were analyzed 56 days after the end of the immunization process. No differences between the groups were observed in the antibody levels. During the intervention, 19 subjects had COVID-19 (11 receiving K8 vs. 8 receiving placebo, p = 0.457). Subgroup analysis in these patients showed that levels of IgG were significantly higher in those receiving K8 compared to placebo (p = 0.038). Among subjects >85 yrs that did not get COVID-19, administration of K8 tended to increase the IgA levels (p = 0.082). The administration of K8 may enhance the specific immune response against COVID-19 and may improve the COVID-19 vaccine-specific responses in elderly populations.

Efficacy of a microencapsulated iron pyrophosphate-fortified fruit juice: a randomised, double-blind, placebo-controlled study in Spanish iron-deficient women.

Fe-deficiency anaemia is a worldwide health problem. We studied the influence of consuming an Fe-fortified fruit juice on Fe status in menstruating women. A randomised, double-blind, placebo-controlled study of 16 weeks of duration was performed. Subjects were randomised into two groups: the P group (n 58) or the F group (n 64), and consumed, as a supplement to their usual diet, 500 ml/d of a placebo fruit juice or an Fe-fortified fruit juice, respectively. The Fe-fortified fruit juice, containing microencapsulated iron pyrophosphate, provided 18 mg Fe/d (100 % of the RDA). At baseline and monthly, dietary intake, body weight and Fe parameters were determined: total erythrocytes, haematocrit, mean corpuscular volume (MCV), red blood cell distribution width (RDW), Hb, serum Fe, serum ferritin, serum transferrin, transferrin saturation, soluble transferrin receptor (sTfR) and zinc protoporphyrin (ZnPP). The fruit juice consumption involved increased intake of carbohydrates and vitamin C, and increased BMI within normal limits. Ferritin was higher in the F group after week 4 (P < 0·05) and became 80 % higher than in the P group after week 16 (P < 0·001), and transferrin decreased in the F group compared with the P group after week 4 (P < 0·001). RDW was higher at weeks 4 and 8 in the F group compared with the P group (P < 0·05). Transferrin saturation increased after week 8, and haematocrit, MCV and Hb increased after week 12, in the F group compared with the P group. Serum Fe did not change. sTfR and ZnPP decreased in the F group at week 16 (P < 0·05). Iron pyrophosphate-fortified fruit juice improves Fe status and may be used to prevent Fe-deficiency anaemia.

Evaluation of the Effect of Limosilactobacillus fermentum CECT5716 on Gastrointestinal Infections in Infants: A Systematic Review and Meta-Analysis.

Reducing the incidence of gastrointestinal infections (GIs) that occur at early stages to mitigate hospitalizations and treatments with adverse effects is a promising strategy for providing well-being to infants and their families. This systematic review and meta-analysis explores whether the early administration of Limosilactobacillus fermentum CECT5716 might be effective as a preventive therapy for GIs. We reviewed the literature to identify randomized controlled trials (RCTs) investigating the effectiveness of milk formulas supplemented with L. fermentum CECT5716 administered to infants at early stages to reduce the incidence of GIs. The MEDLINE (via PubMed), Web of Science (WoS), and Cochrane Central Register of Controlled Trials (via CENTRAL) databases were searched up to 15 June 2021. GI data from the included studies were synthesized in a random-effects model. Three RCTs were finally selected including 435 infants. There was a significant reduction in the incidence rate of GIs for those receiving L. fermentum CECT5716 compared with those receiving placebo (IRR: 0.52, 95% CI: 0.36-0.74, p = 0.0004). Heterogeneity between studies was moderate (I2 = 54.5%). Based on the present systematic review and meta-analysis, the administration of L. fermentum CECT5716 at doses from 1 × 109 to 8.4 × 108 cfu/day in milk formulas may prevent GIs in infants up to 12 months old. Longer-term studies including a higher number of infants are needed to determine whether the use of this probiotic during the early stages of life is an efficient way to reduce the incidence of GIs.

Effects of a Combination of Extracts from Olive Fruit and Almonds Skin on Oxidative and Inflammation Markers in Hypercholesterolemic Subjects: A Randomized Controlled Trial.

Hydroxytyrosol (HT) from olives and polyphenols from almond skin (ASPs) possess cardioprotective properties. This pilot study evaluates the effect of supplementation with a combination of olive fruit and almond skin extracts on low-density lipoprotein (LDL) cholesterol oxidation, lipid homeostasis, and inflammatory parameters in adults with moderate hypercholesterolemia. A randomized, parallel, double-blind, placebo-controlled pilot study of 8 weeks was performed. The extract group (EG) received the supplement with 7.5 mg HT +210 mg ASPs, and the control group (CG) received a placebo composed of maltodextrin. Oxidized LDL (oxLDL) levels and the oxLDL/LDL ratio were lower in the EG than in the CG after 8 weeks of treatment (18.76 ± 3.91 vs. 10.34 ± 4.22, P < .001 and 0.151 ± 0.025 vs. 0.08 ± 0.023, P < .001, respectively). Interleukin-1ß levels were significantly higher in the CG than in the EG at week 4 (P = .004), IL-6 was significantly higher in the CG than in the EG at week 4 (P = .049), and IL-10 was significantly increased at week 4 in both groups (P = .002 for CG and P = .001 for EG). In conclusion, daily consumption of a combination of an olive fruit extract and an almond skin extract for 8 weeks seems to protect LDL from oxidation and to prevent inflammatory status in moderately hypercholesterolemic subjects.

Ultra-processed Food Consumption and Incident Frailty: A Prospective Cohort Study of Older Adults.

BACKGROUND: Ultra-processed food intake has been associated with chronic conditions and mortality. The aim of this study was to assess the relationship between ultra-processed food intake and incident frailty in community-dwelling older adults. METHODS: Prospective cohort study with 1,822 individuals aged at least 60 years who were recruited during 2008-2010 in Spain. At baseline, food consumption was obtained using a validated computerized face-to-face dietary history. Ultra-processed foods were identified according to the nature and extent of their industrial processing (NOVA classification). In 2012, incident frailty was ascertained based on Fried's criteria. Statistical analyses were performed with logistic regression and adjusted for the main potential confounders. RESULTS: After a mean follow-up of 3.5 years, 132 cases of frailty were identified. The fully adjusted risks of frailty across increasing quartiles of the percentage of total energy intake from ultra-processed foods were the following: 0.04 (0.02-0.05), 0.05 (0.03-0.07), 0.09 (0.07-0.12), and 0.11 (0.08-0.14). Results were similar when food consumption was expressed as gram per day/body weight. Regarding ultra-processed food groups, the highest versus the lowest tertiles of consumption of yogurts and fermented milks, cakes and pastries, as well as nonalcoholic beverages (instant coffee and cocoa, packaged juices, and other nonalcoholic drinks, excluding soft drinks) were also significantly related to incident frailty. CONCLUSIONS: Consumption of ultra-processed foods is strongly associated with frailty risk in older adults. Substituting unprocessed or minimally processed foods for ultra-processed foods would play an important role in the prevention of age-related frailty. TRIAL REGISTRATION: NCT02804672.

Consumption of Ultra-Processed Foods and Mortality: A National Prospective Cohort in Spain.

OBJECTIVE: To assess the prospective association between ultra-processed food consumption and all-cause mortality and to examine the effect of theoretical iso-caloric non-processed foods substitution. PATIENTS AND METHODS: A population-based cohort of 11,898 individuals (mean age 46.9 years, and 50.5% women) were selected from the ENRICA study, a representative sample of the noninstitutionalized Spanish population. Dietary information was collected by a validated computer-based dietary history and categorized according to their degree of processing using NOVA classification. Total mortality was obtained from the National Death Index. Follow-up lasted from baseline (2008-2010) to mortality date or December 31th, 2016, whichever was first. The association between quartiles of consumption of ultra-processed food and mortality was analyzed by Cox models adjusted for the main confounders. Restricted cubic-splines were used to assess dose-response relationships when using iso-caloric substitutions. RESULTS: Average consumption of ultra-processed food was 385 g/d (24.4% of the total energy intake). After a mean follow-up of 7.7 years (93,599 person-years), 440 deaths occurred. The hazard ratio (and 95% CI) for mortality in the highest versus the lowest quartile of ultra-processed food consumption was 1.44 (95% CI, 1.01-2.07; P trend=.03) in percent of energy and 1.46 (95% CI, 1.04-2.05; P trend=.03) in grams per day per kilogram. Isocaloric substitution of ultra-processed food with unprocessed or minimally processed foods was associated with a significant nonlinear decrease in mortality. CONCLUSION: A higher consumption of ultra-processed food was associated with higher mortality in the general population. Furthermore, the theoretical iso-caloric substitution ultra-processed food by unprocessed or minimally processed foods would suppose a reduction of the mortality risk. If confirmed, these findings support the necessity of the development of new nutritional policies and guides at the national and international level. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01133093.