There is growing interest in relating taste perception to diet and healthy aging. However, there is still limited information on the influence of age, sex and genetics on taste acuity as well as on ...the relationship between taste perception and taste preferences. We have analysed the influence of age on the intensity rating of the five basic tastes: sweet, salty, bitter, sour and umami (separately and jointly in a "total taste score") and their modulation by sex and genetics in a relatively healthy population (men and women) aged 18⁻80 years (
= 1020 Caucasian European participants). Taste perception was determined by challenging subjects with solutions of the five basic tastes using standard prototypical tastants (6-n-propylthiouracil (PROP), NaCl, sucrose, monopotassium glutamate and citric acid) at 5 increasing concentrations (I to V). We also measured taste preferences and determined the polymorphisms of the genes taste 2 receptor member 38 (TAS2R38), taste 1 receptor member 2 (TAS2R38) and sodium channel epithelial 1 beta subunit (SCNN1B), as TAS2R38-rs713598, TAS1R2-rs35874116 and SCNN1B-rs239345 respectively. We found a statistically significant decrease in taste perception ("total taste score") with increasing age for all the concentrations analysed. This association was stronger for the higher concentrations (
= 0.028;
= 0.012;
= 0.005;
= 4.20 × 10
and
= 1.48 × 10
, for I to V in the multivariable-adjusted models). When we analysed taste qualities (using concentration V), the intensity rating of all the 5 tastes was diminished with age (
0.05 for all). This inverse association differed depending on the test quality, being higher for bitter (PROP) and sour. Women perceived taste significantly more intense than men (
= 1.4 × 10
for total taste score). However, there were differences depending on the taste, umami being the lowest (
= 0.069). There was a complex association between the ability to perceive a taste and the preference for the same. Significant associations were, nevertheless, found between a higher perception of sour taste and a higher preference for it in women. In contrast, the higher perception of sweet was significantly associated with a higher preference for bitter in both, men and women. The TAS2R38-rs713598 was strongly associated with bitter (PROP) taste (
= 1.38 × 10
), having a significant interaction with sex (
= 0.030). The TAS1R2-rs35874116 was not significantly associated with sweet, whereas the SCNN1B-rs239345 was associated (
= 0.040) with salty taste. In conclusion, the inverse association between age and perceived taste intensity as well as the additional influence of sex and some genetic polymorphisms give rise to large inter-individual differences in taste perception and taste preferences that should be taken into account in future studies and for applications in precision nutrition for healthy aging.
Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. The genetics of POAG are complex, and population-specific effects have been reported. Although many polymorphisms ...associated with POAG risk have been reported, few studies have analyzed their additive effects. We investigated, in a southern European Mediterranean population, the association between relevant POAG polymorphisms, identified by initial genome-wide association studies (GWASs) and POAG risk, both separately and as an aggregated multi-locus genetic risk score (GRS). Also, bearing in mind that oxidative stress is a factor increasingly recognized in the pathogenesis of POAG, we analyzed the potential association of the GRS with plasma concentrations of antioxidant vitamins (C and E). We carried out a case-control study including 391 POAG cases and 383 healthy controls, and analyzed four genetic polymorphisms (rs4656461-
, rs4236601-
/
, rs2157719-
and rs3088440-
). An unweighted GRS including the four non-linked polymorphisms was constructed. A strong association between the GRS and POAG risk was found. When three categories of the GRS were considered, subjects in the top category of the GRS were 2.92 (95% confidence interval (CI): 1.79-4.77) times more likely to have POAG compared with participants in the bottom category (
< 0.001). Moreover, the GRS was inversely correlated with plasma vitamin C (
= 0.002) and vitamin E (
= 0.001) concentrations, even after additional adjustment for POAG status. In conclusion, we have found a strong association between the GRS and POAG risk in this Mediterranean population. While the additional correlation found between GRS and low levels of vitamins C and E does not indicated a causal relationship, it does suggest the need for new and deeper research into the effects of oxidative stress as a potential mechanism for those associations.
Many early studies presented beneficial effects of polyunsaturated fatty acids (PUFA) on cardiovascular risk factors and disease. However, results from recent meta-analyses indicate that this effect ...would be very low or nil. One of the factors that may contribute to the inconsistency of the results is that, in most studies, genetic factors have not been taken into consideration. It is known that fatty acid desaturase (
gene cluster in chromosome 11 is a very important determinant of plasma PUFA, and that the prevalence of the single nucleotide polymorphisms (SNPs) varies greatly between populations and may constitute a bias in meta-analyses. Previous genome-wide association studies (GWAS) have been carried out in other populations and none of them have investigated sex and Mediterranean dietary pattern interactions at the genome-wide level. Our aims were to undertake a GWAS to discover the genes most associated with serum PUFA concentrations (omega-3, omega-6, and some fatty acids) in a scarcely studied Mediterranean population with metabolic syndrome, and to explore sex and adherence to Mediterranean diet (MedDiet) interactions at the genome-wide level. Serum PUFA were determined by NMR spectroscopy. We found strong robust associations between various SNPs in the
cluster and omega-3 concentrations (top-ranked in the adjusted model:
-rs174547,
= 3.34 × 10
;
-rs174550,
= 5.35 × 10
;
-rs1535,
= 5.85 × 10
;
-rs174546,
= 6.72 × 10
;
-rs174546,
= 9.75 × 10
;
- rs174576,
= 1.17 × 10
;
-rs174577,
= 1.12 × 10
, among others). We also detected a genome-wide significant association with other genes in chromosome 11:
(myelin regulatory factor)-rs174535,
= 1.49 × 10
;
(transmembrane protein 258)-rs102275,
= 2.43 × 10
;
(flap structure-specific endonuclease 1)-rs174538,
= 1.96 × 10
). Similar genome-wide statistically significant results were found for docosahexaenoic fatty acid (DHA). However, no such associations were detected for omega-6 PUFAs or linoleic acid (LA). For total PUFA, we observed a consistent gene*sex interaction with the
(deoxynucleotidyl transferase terminal interacting protein 2)-rs3747965
= 1.36 × 10
. For adherence to MedDiet, we obtained a relevant interaction with the
(malic enzyme 1) gene (a gene strongly regulated by fat) in determining serum omega-3. The top-ranked SNP for this interaction was
-rs3798890 (
= 2.15 × 10
). In the regional-wide association study, specifically focused on the
and
(fatty acid elongase) 2/
5 regions, we detected several statistically significant associations at
< 0.05. In conclusion, our results confirm a robust role of the
cluster on serum PUFA in this population, but the associations vary depending on the PUFA. Moreover, the detection of some sex and diet interactions underlines the need for these associations/interactions to be studied in all specific populations so as to better understand the complex metabolism of PUFA.
Aging is a risk factor for several pathologies, restricting one's health span, and promoting chronic diseases (e.g., cardiovascular and neurodegenerative diseases), as well as cancer. Telomeres are ...regions of repetitive DNA located at chromosomal ends. Telomere length has been inversely associated with chronological age and has been considered, for a long time, a good biomarker of aging. Several lifestyle factors have been linked with telomere shortening or maintenance. However, the consistency of results is hampered by some methodological issues, including study design, sample size, measurement approaches, and population characteristics, among others. Therefore, we aimed to systematically review the current literature on the effects of three relevant lifestyle factors on telomere length in human adults: physical activity, smoking, and sleep. We conducted a qualitative systematic review of observational and intervention studies using the Preferred Reporting Item for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The systematic literature search covered articles published in MEDLINE and EMBASE databases (from 2010 to 2020). A total of 1400 studies were identified; 83 were included after quality control. Although fewer sedentary activities, optimal sleep habits, and non- or ex-smoker status have been associated with less telomere shortening, several methodological issues were detected, including the need for more targeted interventions and standardized protocols to better understand how physical activity and sleep can impact telomere length and aging. We discuss the main findings and current limitations to gain more insights into the influence of these lifestyle factors on the healthy aging process.
A major problem with dietary assessments is their subjective nature. Untargeted metabolomics and new technologies can shed light on this issue and provide a more complete picture of dietary intake by ...measuring the profile of metabolites in biological samples. Oranges are one of the most consumed fruits in the world, and therefore one of the most studied for their properties. The aim of this work was the application of untargeted metabolomics approach with the novel combination of ion mobility separation coupled to high resolution mass spectrometry (IMS-HRMS) and study the advantages that this technique can bring to the area of dietary biomarker discovery, with the specific case of biomarkers associated with orange consumption (
) in plasma samples taken during an acute intervention study (consisting of a randomized, controlled crossover trial in healthy individuals). A total of six markers of acute orange consumption, including betonicines and conjugated flavonoids, were identified with the experimental data and previous literature, demonstrating the advantages of ion mobility in the identification of dietary biomarkers and the benefits that an additional structural descriptor, as the collision cross section value (CCS), can provide in this area.
Adiponectin is gaining renewed interest since, in addition to its possible protective role against insulin resistance and arteriosclerosis, recent studies suggest other additional favorable effects. ...However, the influence of gene-diet interactions on plasma adiponectin levels is still little understood. We analyzed the association between plasma adiponectin levels and various metabolic traits in a high-cardiovascular risk Mediterranean population, as well as the genetic effect of four candidate single-nucleotide polymorphisms (SNPs) in the adiponectin gene (
) and their interactions with the Mediterranean dietary pattern. Additionally, we explored, at the genome-wide level, the SNPs most associated with plasma adiponectin levels, as well as gene-diet interactions with the Mediterranean diet. In the 954 participants studied (aged 55-80 years), plasma adiponectin levels were strongly associated with plasma HDL-C concentrations (
= 6.6 × 10
) and inversely related to triglycerides (
= 4.7 × 10
), fasting glucose (
= 3.5 × 10
) and type 2 diabetes (
= 1.4 × 10
). Of the four pre-selected
candidate SNPs, the one most associated with plasma adiponectin was the -11391G > A (rs17300539) promoter SNP (
= 7.2 × 10
, in the multivariable adjusted model). No significant interactions with the Mediterranean diet pattern were observed for these SNPs. Additionally, in the exploratory genome-wide association study (GWAS), we found new SNPs associated with adiponectin concentrations at the suggestive genome-wide level (
< 1 × 10
) for the whole population, including the lead SNP rs9738548 (intergenic) and rs11647294 in the
(Vesicle Amine Transport 1 Like) gene. We also found other promising SNPs on exploring different strata such as men, women, diabetics and non-diabetics (
= 3.5 × 10
for rs2850066). Similarly, we explored gene-Mediterranean diet interactions at the GWAS level and identified several SNPs with gene-diet interactions at
< 1 × 10
. A remarkable gene-diet interaction was revealed for the rs2917570 SNP in the
(Opioid Binding Protein/Cell Adhesion Molecule Like) gene, previously reported to be associated with adiponectin levels in some populations. Our results suggest that, in this high-cardiovascular risk Mediterranean population, and even though adiponectin is favorably associated with metabolic traits and lower type 2 diabetes, the gene variants more associated with adiponectin may be population-specific, and some suggestive gene-Mediterranean diet interactions were detected.
Circadian rhythms regulate the sleep-wake and feeding-fasting cycles. Sleep and feeding constitute a complex cycle that is determined by several factors. Despite the importance of sleep duration and ...mealtimes for many obesity phenotypes, most studies on dietary patterns have not investigated the contribution of these variables to the phenotypes analyzed. Likewise, they have not investigated the factors related to sleep or mealtimes. Thus, our aims were to investigate the link between taste perception and eating/sleep patterns and to analyze the effect of the interactions between sleep/meal patterns and genetic factors on obesity phenotypes. We conducted a cross-sectional analysis on 412 adults from the Mediterranean population. We measured taste perception (bitter, sweet, salty, sour, and umami) and assessed sleep duration and waketime. The midpoint of sleep and social jetlag was computed. From the self-reported timing of meals, we estimated the eating window, eating midpoint, and eating jetlag. Adherence to the Mediterranean diet was measured with a validated score. Selected polymorphisms in the TAS2R38, CLOCK, and FTO genes were determined, and their associations and interactions with relevant phenotypes were analyzed. We found various associations between temporal eating, sleep patterns, and taste perception. A higher bitter taste perception was associated with an earlier eating midpoint (
= 0.001), breakfast time (
= 0.043), dinner time (
= 0.009), waketime (
< 0.001), and midpoint of sleep (
= 0.009). Similar results were observed for the bitter taste polymorphism TAS2R38-rs713598, a genetic instrumental variable for bitter perception, increasing the causality of the associations. Moreover, significant gene-sleep interactions were detected between the midpoint of sleep and the TAS2R38-rs713598 (
= 0.032), FTO-rs9939609 (
= 0.037), and CLOCK-rs4580704 (
= 0.004) polymorphisms which played a role in determining obesity phenotypes. In conclusion, our study provided more information on the sleep and mealtime patterns of the general Spanish Mediterranean population than on their main relationships. Moreover, we were able to show significant associations between taste perception, specifically bitter taste; sleep time; and mealtimes as well as an interaction between sleep time and several genetic variants linked to obesity phenotypes. However, additional research is needed to better characterize the causality and mechanisms behind these associations.
Taste perception is a primary driver of food choices; however, little is known about how perception of all five tastes (sweet, salt, sour, bitter, umami) collectively inform dietary patterns. Our aim ...was to examine the associations between a multivariable measure of taste perception-taste perception profiles-and empirically derived dietary patterns. The cohort included 367 community-dwelling adults (55-75 years; 55% female; BMI = 32.2 ± 3.6 kg/m
) with metabolic syndrome from PREDIMED-Plus, Valencia. Six taste perception profiles were previously derived via data-driven clustering (Low All, High Bitter, High Umami, Low Bitter and Umami, High All But Bitter, High All But Umami); three dietary patterns were derived via principal component analysis (% variance explained = 20.2). Cross-sectional associations between profiles and tertials of dietary pattern adherence were examined by multinomial logistic regression. Overall, there were several significant differences in dietary pattern adherence between profiles: the vegetables, fruits, and whole grains pattern was significantly more common for the High All But Umami profile (OR range for high vs. low adherence relative to other profiles (1.45-1.99; 95% CI minimum lower, maximum upper bounds: 1.05, 2.74), the non-extra virgin olive oils, sweets, and refined grains pattern tended to be less common for Low All or High Bitter profiles (OR range: 0.54-0.82), while the alcohol, salty foods, and animal fats pattern tended to be less common for Low Bitter and Umami and more common for High All But Bitter profiles (OR range: 0.55-0.75 and 1.11-1.81, respectively). In conclusion, among older adults with metabolic syndrome, taste perception profiles were differentially associated with dietary patterns, suggesting the benefit of integrating taste perception into personalized nutrition guidance.
Several studies have shown that a low magnesium (Mg) intake in the diet is associated with greater cardiovascular risk and greater risk of diabetes. However, the results are not consistent in all ...populations. To minimize the biases derived from diet measurement, more objective biomarkers of magnesium status have been proposed. Although there is still no ideal biomarker for Mg, several studies have shown that plasma Mg concentrations could be a relatively acceptable biomarker for cardiovascular risk assessment. However, further studies are required to better characterize this marker in different populations. Our aim was to analyze the association between plasma Mg concentrations (measured through inductively coupled plasma mass spectrometry (ICP-MS)) methods, and cardiovascular risk factors in individuals from a general Mediterranean population (aged 18-80 years). The influence of demographic and lifestyle variables, including adherence to the Mediterranean diet, on plasma Mg concentrations was analyzed. The mean Mg level of the population studied was 0.77 ± 0.08 mmol/L, the prevalence of hypomagnesemia (<0.70 mmol/L) being 18.6%. We did not find any statistically significant differences between plasma Mg concentrations and sex, age, tobacco smoking and total adherence to the Mediterranean diet (
> 0.05). We found a statistically significant association between plasma Mg concentrations and the prevalence of type-2 diabetes (0.77 ± 0.08 mmol/L in non-diabetics versus 0.73 ± 0.13 mmol/L in diabetics;
= 0.009). Despite the low prevalence of type-2 diabetes in this population (11.24% in subjects with hypomagnesemia versus 3.91%, in normomagnesemia;
= 0.005), hypomagnesemia was associated with greater odds of being diabetic in comparison with normomagnesemia (OR = 3.36;
= 0.016, even after adjustment for sex, age, obesity, and medications). On the other hand, no statistically significant association of plasma Mg concentrations with obesity, hypertension, fasting triglycerides, HDL-cholesterol or uric acid was found. However, in contrast to what was initially expected, a statistically significant association was found between plasma Mg concentrations (basically in the highest quartile) and greater total cholesterol (
< 0.05) and LDL-cholesterol concentrations (
< 0.05). In conclusion, our results contribute to increasing the evidence gathered by numerous studies on the inverse association between hypomagnesemia and type-2 diabetes, as well as to the observation, previously reported in some studies, of a direct association with hypercholesterolemia. This paradoxical link should be deeply investigated in further studies.
Oxidatively induced DNA damage, an important factor in cancer etiology, is repaired by oxyguanine glycosylase 1 (OGG1). The lower repair capacity genotype (homozygote Cys326Cys) in the OGG1-rs1052133 ...(Ser326Cys) polymorphism has been associated with cancer risk. However, no information is available in relation to cancer mortality, other causes of death, and modulation by diet.
Our aim was to evaluate the association of the OGG1-rs1052133 with total, cancer, and cardiovascular disease (CVD) mortality and to analyze its modulation by the Mediterranean diet, focusing especially on total vegetable intake as one of the main characteristics of this diet.
Secondary analysis in the PREDIMED (Prevención con Dieta Mediterránea) trial is a randomized, controlled trial conducted in Spain from 2003 to 2010.
Study participants (n=7,170) were at high risk for CVD and were aged 55 to 80 years.
Participants were randomly allocated to two groups with a Mediterranean diet intervention or a control diet. Vegetable intake was measured at baseline.
Main outcomes were all-cause, cancer, and CVD mortality after a median follow-up of 4.8 years.
Multivariable-adjusted Cox regression models were fitted.
Three hundred eighteen deaths were detected (cancer, n=127; CVD, n=81; and other, n=110). Cys326Cys individuals (prevalence 4.2%) presented higher total mortality rates than Ser326-carriers (P=0.009). The multivariable-adjusted hazard ratio for Cys326Cys vs Ser326-carriers was 1.69 (95% CI 1.09 to 2.62; P=0.018). This association was greater for CVD mortality (P=0.001). No relationship was detected for cancer mortality in the whole population (hazard ratio 1.07; 95% CI 0.47 to 2.45; P=0.867), but a significant age interaction (P=0.048) was observed, as Cys326Cys was associated with cancer mortality in participants <66.5 years (P=0.029). Recessive effects limited our ability to investigate Cys326Cys×diet interactions for cancer mortality. No statistically significant interactions for total or CVD mortality were found for the Mediterranean diet intervention. However, significant protective interactions for CVD mortality were found for vegetable intake (hazard ratio interaction per standard deviation 0.42; 95% CI 0.18 to 0.98; P=0.046).
In this population, the Cys326Cys-OGG1 genotype was associated with all-cause mortality, mainly CVD instead of cancer mortality. Additional studies are needed to provide further evidence on its dietary modulation.