Introduction: Polyunsaturated fatty acids have always been beneficial for various health purpose. This study is mainly focussed on importance of PUFAs in improving fertility and overall reproductive health of both males and females.Omega-3 reduces inflammation and supports endometrial receptivity, while Omega-6 contributes to ovarian steroidogenesis but may be proinflammatory in excess. Sperm require high PUFA content for membrane fluidity, essential for fertilization 1. The ratio of omega -6 and omega 3 is also important in body for good reproductive health. Lower omega-6 to omega-3 PUFA ratio has been associated with improved sperm quality 2. Previous studies mostly involved the populations undergoing infertility treatment that is assisted reproductive technology, limiting the chance to make it a general notion 3. Therefore, in this prospective population-based cohort study from preconception onward, first aim is to investigate the associations between periconception dietary intake of PUFA-rich foods in both females and males from the general population with fecundability and subfertility risk. Second, to explore whether observed associations were related to dietary PUFA intake, the examination of associations of dietary omega-3 and omega-6 PUFA intake in females and males with these fertility outcomes directly is done 4. Materials and Methods- Generation R Next Study is a population-based prospective cohort study from the preconception period onwards is taken for the research .The food frequency questionnaire is filled by the participants4. Written informed consent was obtained from participating females and males. In total, 1054 unique females who enrolled between 2017 and 2021 had information on dietary intake. Of these, 830 unique females had information on time to pregnancy, with 651 unique females having male partners who also provided information on dietary intake. Periconception PUFA-rich food intake and dietary PUFAs in females and males were assessed. Time to pregnancy and mode of conception were assessed through questionnaires in preconception and early pregnancy. Time to pregnancy was categorized in 2 groups:

Cardiovascular disease remains a leading cause of mortality globally, with deaths increasing from 12.4 million in 1990 to 19.8 million in 2022. In Europe, there are more than 10 million new cases diagnosed annually. Atherosclerotic plaques accumulate in the vessels, particularly the arterial vessels, resulting in a condition called atherosclerotic cardiovascular disease, or ASCVD, which has a substantial impact on healthcare because it causes premature death. The main clinical health implications of it are ischaemic heart disease (IHD), ischaemic stroke and peripheral arterial disease (PAD). Vitamin D is an important fat-soluble vitamin synthesised in skin by UV-B rays from sunlight. It regulates immune, cellular and metabolic functioning . Vitamin D is also absorbed by fatty fish, dairy products or supplements. After absorption, vitamin D gives out 25-hydroxyvitamin D by hydroxylation in the liver that is considered as serum biomarker of vitamin D level in individuals. Studies show a positive association of low serum 25(OH)D level and increased risk of CVD and other risk factors. They have their limitations, such as the small size of participants, limited covariates and especially no proof of having real-world application and effectiveness. This uncertainty is the basis of the aim of this research study on the European population. The primary goal is to systematically examine the cause-effect relationship of regular intake of vitamin D supplements and IHD, cerebrovascular disease including ischemic stroke, PAD and artherosclerotic disease leading to endpoint ASCVD using the prospective cohort study of UK Biobank. Materials and Methods- 5,00,000 participants of age group 40-69 years from the timeframe 2006-2010 initially selected, and only 4,09,822 participants were moved forward with the follow-up studies after exclusion because of lack of data. Prior data was collected that is baseline characteristics, vitamin D intake, serum concentration of 25(OH)D measured using chemiluminescent immunoassay and ASCVD occurrence in participants after more than 15 years using hospital admission and primary care records for signs and symptoms. Covariates selected included demographics like age, sex, physical activity, socioeconomic condition. lifestyle of the participant , clinical biomarkers after blood, urine sample evaluation and other vitamin D specific factors. For statistical analysis, cox proportional hazards regression models are created. Model 1 is plotted adjusting variables age and sex. Model 2 is made by using other 40+ covarites. The hazard ratios estimated by competing all-cause mortality for ASCVD outcomes. A false discovery rate of <0.05 is taken for statistical significance. Results The findings suggested that around 20.7% participants are Vitamin D deficient and more than 30% are insufficient; only 4.3% had a sufficient regular intake of vitamin D. The follow-up of 15+ years suggested that 11.6% of participants developed ASCVD. Vitamin D deficiency that is

Cognitive dysfunctioning is exponentially increasing in the modern population due to reasons ranging from overuse of technology to sedentary lifestyle and lack of physical activity to name a few. In the case of the older population it has been observed to be more prevalent. Hence the understanding of linking factors of brain health , age and diet has been gaining importance. Some factors that are recognized are lack of micronutrients in the diet of old age people. The reason can be loss of appetite, energy being utilised in hard physical activity, loss of teeth and swallowing ability and so on. Vitamins B, D and E have been found to imbibe protective abilities especially on cognitive performance. Another vitamin that is under limelight for directly affecting cognitive health is Vitamin B1. Its deficiency causes neurodegenerative disorders including Alzheimer’s disease, Parkinson’s disease and Huntington’s disease. Here in this research study the main focus is to check the relationship among vitamin B1 and mental development along that of various diseases. Materials and Methods The observational study is done cross-sectionally from the data of 2422 participants aged equal to or more than 60 years of age from National Health and Nutrition Examination Survey (NHANES) 2011-2014. For data collection, 24hr dietary recall method done for average vitamin B1 intake assessment and cognitive function tests namely Digit Symbol Substitution Test (DSST), Animal Fluency Test(AFT) and CERAD done for understanding brain health and functioning. Covariates taken are age, gender, BMI, income, history of lifestyle disease on the basis of which multivariate regression models were established. For all the tests, high scores is the direct indicative of better cognitive performance. Results- The participants were divided into 4 groups on the basis of the amount of intake of Vitamin B1 in the period of the study analysis. Henceforth it as observed that Q4 group that had highest daily consumption of B1 rich foods indicated better results in case of cognitive performance including speed and visual memory by the average of 48.3 ± 15.7, 17.6 ± 5.7, and 0.10 (−0.44, 0.57) respectively in DSST, AFT and global z scores . This is a significantly positive association among all the factors taken in this research study highlighting the need of sufficient good amounts of B1 rich foods in the diet of older adults to prevent the onset of mental disorders. Previous health reports of diabetes and coronary heart disease affect this result. No significant interactions are present among dietary vitamin B1 intake and participant characteristics or any other lifestyle diseases. Conclusion- Vitamin B1 is one of the most important micronutrients essentially present in our diets but often neglected due to unawareness. It plays an important role in oxidation, glucose metabolism and neural functioning. The consumption gets decreased in case of elderly people hence elevating the risk of having neurological disorders of symptoms like paralysis, ataxia and confusion.

Some of the top causes of mortality all over the world include cardiovascular diseases like coronary artery disease (CAD), hypertension, heart failure and stroke to name a few. The one factor that influences the most is diet and nutrition availability. Macronutrients that are carbohydrates, fats, proteins play a crucial role in cardiovascular health and overall metabolism of a person. However there were not any significantly perfect results showing direct influence on each other due to some of the confounding factors namely genetics, lifestyle choices, physical activity and differences based on population. Previous data point out that Low carbs intake improves cardiometabolic functioning while moderate diet is inversely linked to CVD risk. Cardiovascular benefits are associated with high plant protein intake but incase of fat, high fat food indicated damage in heart but there has been a significant number of conflicting studies implicating no as such relation. Similar studies are related to the relationship of glucose intake and symptoms like obesity and insulin resistance that fail to explain . All of this data meant that there is a requirement of brand new and longitudinal studies. But it is impractical to conduct such long term diet related study on a larger population hence a approach is to do Mendelian Randomization that represent casual association of CVD risks to that of dietary factors. Materials and Methods The study took 2 established methodology to investigate the relationship of CVD risk factors and diet along with other factorsthat include- Observational analysis from data of NHANES, 2017-2020 (National Health and Nutrition Examination Survey) and Mendelian Randomization analysis. Dietary assessment was done by 24 hour diet recall method and CVD symptoms were reported by subjects. Demographics factors,lifestyle factors and clinical history were assessed as well. For Mendelian Randomization, genetic data were collected from UK Biobank and FinnGen study for the identification of genetic variants associated with macronutrient consumption and CVD risk. The instrumental variables considered were single nucleotide polymorphisms associated with macronutrients. Results and Discussion Multivariable logistic regression analysis was developed to understand the associations adjusted to demographics, lifestyle factors and clinical history. Carbohydrates and sugar intake didn’t express any significant association to heart failure, stroke, CAD, Hypertension. Increased fats only had a lower risk association to heart failure but no relation to other factors causing cardiovascular health. Proteins have reduced risk association to all the symptoms. This presented a robust evidence that higher dietary fat and protein intake are linked to lowering any risk of cardiac problems. Similarly, mendelian randomization analysis expressed genetic variants causing macronutrient intake direct relation to CVD. Fats expressed lower risk association to causing heart failure and Coronary artery disease of OR value 0.85 and 0.90 respectively hence showing an inverse casual relationship .For stroke and hypertension, proteins had a lower risk association signifying a similar inverse casual relationship .Casual relationship is absent in case of carbohydrate and CVD outcome. If compared both observational and MR analyses, it showed similar results of having inverse relation. Protein intake showed beneficial results of reducing chances of stroke and hypertension by both study methods. Furthermore carbs and sugars had no as such positive association to CVD risks by either observational or causal analysis. To ensure the validity of the above results, the study also conducted sensitivity analysis by Cochran’s test by heterogeneity detection wherein no heterogeneity meant genetic variants were valid instrumental variables, MR Egger intercept test gave evidence of no horizontal pleiotropy confirming that only these variables influenced the test results. Other validity test showed that both result findings were consistently similar and the findings were reliable. Conclusion- The study provides robust evidence that increased dietary intake of protein and fat are directly and significantly associated to reduced cardiovascular disease signs and symptoms and all causative factors. These findings shed light on importance of macronutrient balance in daily diet for risk prevention. The goal of future research must be to explore other pathways and personalized nutrition strategies for optimizing overall human health.

An optimal amount of nutrition must be maintained to delay cognitive decline and promote good brain health. It has been proven by some of the previous studies that malnutrition is a common cause as well as a consequence of Alzheimer's disease (AD) that even tends to worsen the disease condition if not treated in advance. Sadly very few studies have been done to check the relationship between Neuropsychotic symptoms (NPS) and nutrition. The symptoms include anxiety, hallucinations, psychosis, agitation, and depression that tend to cause poor cognitive ability, quality of life, and faster disease progression. This paper hypothesizes that probably a shared brain regulation part can explain the reason behind the association between NPS and nutritional status in patients on the AD continuum. For this, patients from Chinese Imaging, Biomarkers, and Lifestyle (CIBL) were taken having amnestic Mild Cognitive Impairment (MCI) and AD dementia (age of onset >60 years). Data related to demographics like age, sex, medical history, clinical diagnosis and anthropometrics, dietary habits, and neuropsychotic symptoms history were collected to create baseline information. Neuroimaging data was also collected for brain center analysis. The brain regions of interest (ROIs) in this study were the regions concerned with and involved in both the homeostatic control and regulation of appetite and cognitive control related to eating. Results and Conclusion: The results revealed that patients with or at risk of malnutrition had a higher frequency of NPS, psychotic symptoms, affective symptoms, hyperactivity, and appetite/ eating disorders (all P

Type 2 Diabetes has been a common problem since decades and research has clearly proven a strong link between type 2 diabetes and changes that occur in gut microbiota. There has been reduced abundance of butyrate-producing bacteria like Faecalibacterium prausnitzii, and Roseburia intestinalis and so is overall microbial diversity as per seen after onset of diabetes that cause more insulin resistance and dysfunctionality of metabolics of body causing a vicious cycle of causes and consequences. Along with it has been observed that there is a direct relation of Type 2 Diabetes to cognitive impairment and dementia as elevated blood sugar negatively affects brain function and memory. Emerging studies suggest that metformin interacts with the gut microbiota , altering bacterial composition in ways that could benefit both metabolic and cognitive health. Evidence from animal and human studies shows that metformin increases beneficial bacteria such as Akkermansia muciniphila while reducing harmful bacteria associated with inflammation. It can be stated that the gut-brain axis has a very important role in this interplay. This study aims to analyse and investigate the relation among these three factors that can have huge benefits in healthcare and treatment of the patients suffering by reducing the symptoms and prevent further decline in health. For this purpose,two independent cohorts of patients are taken each from Aging Imageomics Study (observational, n = 1030) and MEIFLO Study (randomized, double-blind, phase IV pilot study, n = 40). Four study groups for the study of patients and aim of data collection are taken namely, Healthy individuals (n = 172), Long-term T2D patients on metformin (n = 134), patients on other oral hypoglycemics (n = 45), Patients who are recently diagnosed with T2D and are starting metformin doses(n = 22).Inclusion criteria included: age between 18 and 65 years. Neurocognitive tests were employed to evaluate four distinct cognitive domains: attention, executive function, memory, and language. Gut microbiome analysis (shotgun metagenomics) and metabolomics (HPLC-ESI-MS/MS) from fecal and plasma samples were taken for purpose of analysis. Results and Conclusion: First assessment done on the relationships between microbial composition and metformin treatment by comparing metformin-treated T2D subjects with healthy subjects. Results interpret that there has been a positive increase in species of Akkermansia muciniphila, Escherichia coli, Shigella sonnei, Klebsiella pneumoniae to name a few. There was a decrease in bacterial species belonging to the Firmicutes phylum such as Romboutsia timonensis, Romboutsia ilealis, and Roseburia faecis. When stratified this population by sex, the A. muciniphila/R. ilealis ratio was significantly and positively associated with MBT-TFR scores specifically in men that means better memory.Metformin tends to directly affect TCA cycle as well as Butanoate, arginine, and proline metabolism. High proline levels meaning more glutamate metabolism. The paper concludes with the said results that can be interpreted as differences in sex hormones that may explain these differences between men and women as well as slight variation in gut microbiome composition. Along with that, metformin has been proved to have a significant effect on cognition of men. All these results and interpretation can be well utilised in medical treatments of the concerned patients and preparation of personalized treatment methodology. Keywords: Metformin, cognition, Diabetes, Type 2 Diabetes, Memory,

In this study, the goal was to focus on the metabolic and physiological changes in body of older adults that often is the result of change in dietary pattern like avoidance of certain foods, chewing ability, change in taste, digestion problem, mood changes, physical activity levels, reduced uptake of glucose due to insulin resistance. This contributes directly and significantly in development of diabetes due to hyperglycemia-like conditions in the body shown as its diagnostic symptoms of retinopathy and neuropathy. All this heightens the risk of developing Cardiovascular disease by contributing to cardiometabolic disorders along with causing severe damage in other vital organs like kidney and liver. Statistics show that almost 70% of older adults of age above 65 have these risk factors already. Enhanced tendency of heart related issues that may end up as stroke, myocardial infarction to name a few, is a direct impact to elevated hospital risk and mortality risk. In Italy alone diabetes-related complications (hospital admissions, medications, and outpatient care) generate costs of approximately €9 billion annually . Scientist devised that the age related risk factors can be reduced on a certain level by consumption of healthy food items like those rich in polyunsaturated fatty acids. These include vegetarian sources-spinach, flax seed, chia seed, soyabean, walnut and non vegetarian sources- mackerel and salmon. Other health benefits of consumption of PUFAs that include omega 3 and omega 6 rich food items are- regulation of triglycerides and cholesterol levels that have in turn cardioprotective effect. It can help in preventing dementia or Alzheimer's or related neural problems in elderly. These unsaturated fatty acids cause improvement in sperm quality preventing the development of idiopathic oligoasthenoteratozoospermia. They are essential in cell signaling and overall development of the body. Previous studies have failed to observe a clear association among the two factors that is PUFAs’ consumption and onset of diabetes. They got contradicting results as per the scope of each study which either had a small cohort of participants, a narrow age group or other factors like one type of diet, young adults that had almost no risk of diabetes . Study by Hu. M. et.al.(1) showed that there is a positive correlation among the factors but the research was restricted to the Asian population only. However there are very few studies examining Mediterranean diet and population and no study was included in the pooled analysis of recent systematic review and meta analysis. Even Though it has been well known that Mediterranean diet is already consisting of around 35% of grains, 30% vegetables and fruits,a 20% of fishes and poultry, around 10% of olive oil , that makes people living in Mediterranean countries, such as Italians, consuming a moderate-to-high omega-3 PUFAs rich diet. Furthermore just a few investigations have examined samples composed exclusively of older adults. Methodology: The study design includes cross-sectional study of 4461 older adults taken from ongoing Longevity Check-up 8+ project database wherein the adults should be of normal BMI , age 65 years and older . The data collection was done by obtaining information on participant’s lifestyle habits that includes health conditions taken by blood pressure measurements, blood glucose levels, total cholesterol levels, smoking behaviour, physical activity level, along with dietary pattern of the participant. Statistical analysis was done by comparing two of the variables each time and checking the association. Results: The final results showed that the participants had almost 21% prevalence of hypertension, 15.5% diabetes and 15.5% obesity. People having higher dietary intake of eicosapentaenoic acid (EPA), docosahexaenoic acid ( DHA) and combined EPA & DHA, alpha-linolenic acid (ALA) , Omega 6 fatty acids causes reduced blood glucose levels and hence low diabetes prevalence (p value range of 0.001-0.0014) . Omega 6 and ALA consumption reduced systolic blood pressure significantly by p value of 0.001. Hypertension level had less significant relation of negative association with high PUFA consumption. Conclusion: The data concludes that increased consumption of PUFAs specifically EPA and DHA can significantly reduce blood glucose level in participants and hence help to regulate diabetes. Dietary patterns of elderly must be a combined average of adequate levels of calories, protein, micronutrients, omega 6 and omega 3 fatty acids that include ALA, EPA and DHA. This may help in improving cardiometabolic health by reducing blood glucose levels, insulin resistance and prevalence of risk factors like diabetes as well as reducing the severity of damage in other vital organs of the human body that include kidney, heart and liver. Omega 3 inhibits TLR4 pathway that helps to enhance uptake of glucose as well as treating insulin sensitivity and increase expression of proteins involved in signalling pathways of insulin such as insulin receptor and GLUT4. Omega 3 and 6 supplements in the form of capsules are being consumed religiously by people who are now aware of its benefits but more awareness is to be done. Impact of the research: Consumption of PUFAs in diet on a daily basis has a direct consequence of better cardiometabolic health. More research has to be done in the cardiometabolic benefits of omega 3. This study helps to shed light on this area of research but a direct mechanism of action has to be yet devised properly for future benefits to be discovered. Limited time for this study can be improved by providing more time as well as including more tests like the HbA1c test for better results. Keywords: cardiovascular diseases, aging, diabetes, PUFA consumption, Omega 3, Mediterranean diet References- Hu, M., Fang, Z., Zhang, T. et al. Polyunsaturated fatty acid intake and incidence of type 2 diabetes in adults: a dose response meta-analysis of cohort studies. Diabetol Metab Syndr 14, 34 (2022) Coelho-Júnior, Hélio José, et al. "Dietary Intake of Polyunsaturated Fatty Acids Is Associated with Blood Glucose and Diabetes in Community-Dwelling Older Adults." Nutrients 16.23 (2024): 4087.

Telomere length is a reliable biological marker that estimates ageing in people. They are the protective ends of chromosomes that are composed of DNA and protein. When the telomeres get too short with age, it signals the cell to stop dividing causing cellular senescence and hence death. The aim of this study is to establish if there is any solid association between cognitive health and telomere length. This will be further beneficial for early detection and monitoring of cognitive death. Previous studies done in this area found positive associations, while others showed no clear link. One limitation found in previous studies were less number of participants involved hence this study took almost 8000 participants from European background and tried to explore whether measured telomere length (RTL) and genetically predicted telomere length (PGS-TL) are associated with baseline cognitive performance and cognitive changes over time. Methodology Initial data was drawn from 7,877 participants in the PROTECT study, a UK-based longitudinal research initiative focused on aging and cognition. Inclusion criteria was participants should be dementia-free, aged ≥50 years and had access to computers and internet. Data collection was further done in two forms- Relative Telomere Length (RTL): Measured from DNA extracted from saliva samples of 846 participants and Polygenic Scores for Telomere Length (PGS-TL): Computed from genome-wide data for all participants. Cognitive performance was assessed using tests-Paired Associate Learning, Digit Span Test, Self-Ordered Search, Verbal Reasoning. Age, genetics, education level, sex, employment status, taken as covariates. Latent growth models were used to assess cognitive performance from the data of participants. Results The sample was further divided into two groups based on the median age (~62 years) to compare results for middle-aged vs. older adults, No strong or consistent relationships were found between telomere length (RTL or PGS-TL) and baseline cognitive performance or its changes over time. In case of more than 62 years old adults, Longer RTL was weakly associated with worse verbal reasoning performance at baseline, though this finding did not survive statistical correction. Higher PGS-TL predicted slower cognitive improvement in verbal reasoning initially, followed by more rapid improvement after two years. Significant associations were nil between telomere length and cognitive performance when observed in middle aged adults that are 50-62 years old. It was established by the researchers that cognitive scores tend to get improved over time, likely due to the repeated exposure of the patients to cognitive tests rather than genuine cognitive changes. Conclusion It is the first study in this area to examine the relationship between telomere length and longitudinal cognitive performance throughout life, using both measured (RTL) and genetically predicted (PGS-TL) telomere length using a large amount of data set. It is concluded that both telomere lengths do not appear to be a strong predictor of cognitive performance or age-related cognitive changes in older adults. The study emphasizes the need for alternative biomarkers, such as epigenetic clocks, for better prediction of cognitive decline. Overall, the results drew into question the utility of telomere length as an ageing biomarker that is capable of predicting cognitive performance and age-related change, in typically ageing individuals but other alternatives can be used as well. Impact of the research The study challenges previous assumptions that telomere length is a strong predictor of cognitive performance and decline. It suggests that the link between telomere biology and cognitive aging may be weaker or more complex than expected. It emphasizes the need for longer-term studies and more diverse populations to capture the complex dynamics of aging and cognition and promotes the integration of other variables like environmental, genetic, and lifestyle factors in future research on cognitive health.