Walnut (Juglans regia L.) Septum: Assessment of Bioactive Molecules and In Vitro Biological Effects.

Walnut (Juglans regia L.) septum represents an interesting bioactive compound source by-product. In our study, a rich phenolic walnut septum extract, previously selected, was further examined. The tocopherol content determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed higher amounts of α-tocopherol compared to γ- and δ-tocopherols. Moreover, several biological activities were investigated. The in vitro inhibiting assessment against acetylcholinesterase, α-glucosidase, or lipase attested a real management potential in diabetes or obesity. The extract demonstrated very strong antimicrobial potential against Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella enteritidis. It also revealed moderate (36.08%) and strong (43.27%) antimutagenic inhibitory effects against TA 98 and TA 100 strains. The cytotoxicity of the extract was assessed on cancerous (A549, T47D-KBluc, MCF-7) and normal (human gingival fibroblasts (HGF)) cell lines. Flow cytometry measurements confirmed the cytotoxicity of the extract in the cancerous cell lines. Additionally, the extract demonstrated antioxidant activity on all four cell types, as well as anti-inflammatory activity by lowering the inflammatory cytokines (interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1 ß (IL-1ß)) evaluated in HGF cells. To the best of our knowledge, most of the cellular model analyses were performed for the first time in this matrix. The results prove that walnut septum may be a potential phytochemical source for pharmaceutical and food industry.

Process Optimization for Improved Phenolic Compounds Recovery from Walnut (Juglans regia L.) Septum: Phytochemical Profile and Biological Activities.

Plant by-products can be valuable sources of polyphenol bioactive compounds. Walnut (Juglans regia L.) is a very important tree nut rich in biologically active molecules, but its septum was scarcely researched. Experimental data indicated a hypoglycemic effect of septum extracts, with almost no details about its phytochemical composition. The main objectives of this study were: (1) to obtain walnut septum (WS) extracts with high content in bioactive compounds and antioxidant activity based on an original experimental design; (2) characterization of the phytochemical profile of the WS extracts using HPLC-MS/MS; (3) evaluation of the biological potential of the richest polyphenolic WS extract. The variables of the experimental design were: extraction method (maceration and Ultra-Turrax extraction), temperature, solvent (acetone and ethanol), and percentage of water in the solvent. The first quantifiable responses were: total phenolic content, total flavonoid content, condensed tannins, and ABTS antioxidant capacity. The phytochemical profile of lyophilized extracts obtained by Ultra-Turrax extraction (UTE), the most efficient method, was further determined by HPLC-MS/MS analysis of individual polyphenolic and phytosterols compounds. It is the first study to assay the detailed composition of WS in hydrophilic and lipophilic compounds. The biological potential of the richest polyphenolic WS extract was also evaluated by FRAP and DPPH antioxidant capacity and the inhibition of tyrosinase, an enzyme involved in the browning in fruits and vegetables, skin wrinkles and aging. Conclusion: The phytochemical profile of the analyzed extracts proves that WS can be a valuable source of biologically active compounds (polyphenols) for food and/or pharmaceutical industry and warrant the continuation of current research in further evaluating its bioactive potential.

Inhibitory Effect of Citalopram on the Pharmacokinetics of Carvedilol in Rats and in vitro Models.

BACKGROUND/AIMS: The aim of this study was to investigate the drug-drug interaction between carvedilol and citalopram based on carvedilol metabolism in vitro and his pharmacokinetics (PKs) in vivo after the oral administration of the single drug and both drugs, and reveal citalopram effects on the PKs of carvedilol. METHODS: Each rat was cannulated on the femoral vein, prior to being connected to BASi Culex ABC®. Carvedilol was orally administrated in rats (3.57 mg/kg body weight [b.w.]) in the absence of citalopram or after a pre-treatment with multiple oral doses of citalopram (1.42 mg/kg b.w.). Plasma concentrations of carvedilol were determined using high-performance liquid chromatography-MS at the designated time points after drug administration, and the main PK parameters were calculated by noncompartmental analysis. In addition, effects of citalopram on the metabolic rate of carvedilol were investigated using rat-pooled liver microsome incubation systems. RESULTS: During co-administration, significant increases of the area under the plasma concentration-time curve as well as of the peak plasma concentration were observed. The rat-pooled liver microsome incubation experiment indicated that citalopram could decrease the metabolic rate of carvedilol. CONCLUSION: Citalopram co-administration led to a significant alteration of carvedilol's PK profile in rats; it also demonstrated, in vitro, these effects could be explained by the existence of a drug-drug interaction mediated by CYP2D6 inhibition.

Acute toxicity evaluation of a thiazolo arene ruthenium (II) complex in rats.

Recently, a series of thiazolo arene ruthenium complexes were found to be highly cytotoxic in vitro, on both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. The most active compound of the series, [(η(6)-p-cymene)Ru(L)Cl]Cl (L = 1-(2-(2-(3-chlorobenzylidene)hydrazinyl)-4-methylthiazol-5-yl)ethanone), was selected for an in vivo study in order to assess its safety profile. The ruthenium complex was administered to female Crl:WI rats orally, by gastric intubation and intraperitoneal injection. The hematological parameters and the histopathological changes in liver, kidneys, spleen and brain were investigated after a 14-days treatment. The substance was very well tolerated orally, with a LD50 value of over 2000 mg/kg body weight. Symptoms were observed only in the first day after intraperitoneal administration of the highest dose, with a LD50 value between 300 and 2000 mg/kg bw. The hematological profile was not modified at any of the tested doses, after both oral and intraperitoneal acute administration. Structural modifications (moderate lymphocytolysis) were identified only in the spleen at the highest tested dose. In conclusion, the thiazolo arene ruthenium complex was very well tolerated orally and had a low acute toxicity after intraperitoneal administration in Crl:WI rats The results justify further investigation to determine the in vivo therapeutic potential of this promising ruthenium complex.

Influence of Genista tinctoria L. or methylparaben on subchronic toxicity of bisphenol A in rats.

OBJECTIVE: To evaluate the influence of an extract of Genista tinctoria L. herba (GT) or methylparaben (MP) on histopathological changes and 2 biomarkers of oxidative stress in rats subchronicly exposed to bisphenol A (BPA). METHODS: Adult female Wistar rats were orally exposed for 90 d to BPA (50 mg/kg), BPA+GT (35 mg isoflavones/kg) or BPA+MP (250 mg/kg). Plasma and tissue samples were taken from liver, kidney, thyroid, uterus, ovary, and mammary gland after 30, 60, and 90 d of exposure respectively. Lipid peroxidation and in vivo hydroxyl radical production were evaluated by histological analysis along with malondialdehyde and 2,3-dihydroxybenzoic acid detection. RESULTS: The severity of histopathological changes in liver and kidneys was lower after GT treatment than after BPA or BPA+MP treatment. A minimal thyroid receptor antagonist effect was only observed after BPA+MP treatment. The abnormal folliculogenesis increased in a time-dependent manner, and the number of corpus luteum decreased. No significant histological alterations were found in the uterus. The mammary gland displayed specific estrogen stimulation changes at all periods. Both MP and GT revealed antioxidant properties reducing lipid peroxidation and BPA-induced hydroxyl radical generation. CONCLUSION: GT L. extract ameliorates the toxic effects of BPA and is proved to have antioxidant potential and antitoxic effect. MP has antioxidant properties, but has either no effect or exacerbates the BPA-induced histopathological changes.

Investigating the Effects and Mechanisms of Combined Vitamin D and K Supplementation in Postmenopausal Women: An Up-to-Date Comprehensive Review of Clinical Studies.

Aging is a complex process and a significant risk factor for chronic diseases. Menopause, a component of aging in women, is associated with several important cardiometabolic conditions including metabolic syndrome, osteoporosis, and cardiovascular diseases. Menopausal women could benefit from preventative strategies that may decrease morbidity and mortality and improve their quality of life. Vitamins D and K are essential nutrients required for bone health, immune function, and reducing cardiovascular risks, yet their synergistic effect is less understood in aging women. This is the first comprehensive review to summarize the evidence found in randomized clinical trials of the beneficial effects of vitamin D and K co-treatment in postmenopausal women. In our literature search across key electronic databases such as Cochrane, PubMed, and Ovid, we identified 31 pertinent studies. Overall, significant findings indicate that the combined intake of vitamins D and K may positively affect cardiovascular and bone health in postmenopausal women, emphasizing the importance of maintaining a healthy diet rich in vegetables and fermented dairy products. Given the challenges in obtaining all necessary nutrients solely through the diet, vitamin D and K supplements are recommended for postmenopausal women to promote healthy aging and well-being.

Mechanistic Insights into the Biological Effects and Antioxidant Activity of Walnut (Juglans regia L.) Ellagitannins: A Systematic Review.

Walnuts (Juglans regia L.) are an important source of ellagitannins. They have been linked to positive effects on many pathologies, including cardiovascular disorders, neurodegenerative syndromes, and cancer. The limited bioavailability of ellagitannins prevents them from reaching significant circulatory levels, despite their antioxidant, anti-inflammatory, and chemopreventive properties. Urolithins are ellagitannin gut microbiota-derived metabolites. They have better intestinal absorption and may be responsible for the biological activities of ellagitannins. Recent evidence showed that walnut ellagitannins and their metabolites, urolithins, could have positive outcomes for human health. This study aims to synthesize the current literature on the antioxidant activity and mechanistic pathways involved in the therapeutic potential of walnut ellagitannins and their metabolites. In the eligible selected studies (n = 31), glansreginin A, pedunculagin, and casuarictin were the most prevalent ellagitannins in walnuts. A total of 15 urolithins, their glucuronides, and sulfate metabolites have been identified in urine, blood, feces, breast milk, and prostate tissue in analyzed samples. Urolithins A and B were associated with antioxidant, anti-inflammatory, cardioprotective, neuroprotective, anticarcinogenic, and anti-aging activities, both in preclinical and clinical studies. Despite the promising results, further well-designed studies are necessary to fully elucidate the mechanisms and confirm the therapeutic potential of these compounds in human health.

Genes Involved in Susceptibility to Obesity and Emotional Eating Behavior in a Romanian Population.

Obesity, a significant public health concern with high prevalence in both adults and children, is a complex disorder arising from the interaction of multiple genes and environmental factors. Advances in genome-wide association studies (GWAS) and sequencing technologies have identified numerous polygenic causes of obesity, particularly genes involved in hunger, satiety signals, adipocyte differentiation, and energy expenditure. This study investigates the relationship between six obesity-related genes (CLOCK, FTO, GHRL, LEP, LEPR, MC4R) and their impact on BMI, WC, HC, WHR, and emotional eating behavior in 220 Romanian adults. Emotional eating was assessed using the validated Emotional Eating Questionnaire (EEQ). Our analysis revealed significant variability in obesity-related phenotypes and emotional eating behaviors across different genotypes. Specifically, CLOCK/CC, FTO/AA, and LEP/AA genotypes were strongly associated with higher obesity metrics and emotional eating scores, while GHRL/TT and MC4R/CC were linked to increased BMI and WHR. The interplay between genetic predisposition and emotional eating behavior significantly influenced BMI and WHR, indicating a complex relationship between genetic and behavioral factors. This study, the first of its kind in Romania, provides a foundation for targeted interventions to prevent and reduce obesity and suggests potential strategies for gene expression modulation to mitigate the effects of emotional eating. Adopting a 'One Health' approach by creating an evidence base derived from both human and animal studies is crucial for understanding how to control obesity.

Phytochemicals and Biological Activities of Walnut Septum: A Systematic Review.

In the last few decades, scientific evidence has stressed the importance of plants in the prevention and/or supportive treatment of a plethora of diseases, many of them chronic, age-associated disorders. Juglans regia L. is a traditional plant that has been integrated into traditional medicine since ancient times. Due to the presence of biologically active compounds, walnut was used in the treatment of various maladies. Recently, investigations have focused on the walnut by-products and waste products, with research on their valuable constituents and active properties. Among these secondary products, walnut septum was analyzed in several studies, its phytochemical profile described, and some of the biological activities examined. However, compared to other walnut by-products, no comprehensive review to gather all the pertinent scientific knowledge was found in the literature. Therefore, the aim of this study was to critically assess the information furnished by peer-reviewed articles regarding the walnut septum chemical composition and the related biological activities, including antioxidant activities, anti-inflammatory effects, antimicrobial properties, antidiabetic activities, anti-tumor properties, and anti-aging potential. In conclusion, as these preclinical studies showed that walnut septum metabolites were responsible for a wide range of preventive and therapeutic uses, further research should confirm the beneficial outcomes in clinical trials.

The Impact of Ellagitannins and Their Metabolites through Gut Microbiome on the Gut Health and Brain Wellness within the Gut-Brain Axis.

Ellagitannins (ETs) are a large group of bioactive compounds found in plant-source foods, such as pomegranates, berries, and nuts. The consumption of ETs has often been associated with positive effects on many pathologies, including cardiovascular diseases, neurodegenerative syndromes, and cancer. Although multiple biological activities (antioxidant, anti-inflammatory, chemopreventive) have been discussed for ETs, their limited bioavailability prevents reaching significant concentrations in systemic circulation. Instead, urolithins, ET gut microbiota-derived metabolites, are better absorbed and could be the bioactive molecules responsible for the antioxidant and anti-inflammatory activities or anti-tumor cell progression. In this review, we examined the dietary sources, metabolism, and bioavailability of ETs, and analyzed the last recent findings on ETs, ellagic acid, and urolithins, their intestinal and brain activities, the potential mechanisms of action, and the connection between the ET microbiota metabolism and the consequences detected on the gut-brain axis. The current in vitro, in vivo, and clinical studies indicate that ET-rich foods, individual gut microbiomes, or urolithin types could modulate signaling pathways and promote beneficial health effects. A better understanding of the role of these metabolites in disease pathogenesis may assist in the prevention or treatment of pathologies targeting the gut-brain axis.

Phytochemical Profiling and Biological Activities of Quercus sp. Galls (Oak Galls): A Systematic Review of Studies Published in the Last 5 Years.

Quercus species have been widely used in traditional medicine, and recently, researchers' attention has focused on galls of the genus Quercus as a source of health-promoting phytochemicals. This review presents a summary of the most recent findings on the phytochemistry and bioactivity of oak galls, following the screening of scientific papers published in two relevant databases, PubMed and Embase, between January 2018 and June 2023. The oak galls are rich in active compounds, mostly gallotannins and phenolic acids. Due to these secondary metabolites, the reviewed studies have demonstrated a wide range of biological activities, including antioxidant and anti-inflammatory actions, antimicrobial properties, tissue-protective effects, and antitumor, anti-aging, and hypoglycemic potential. Thus, oak galls are a promising natural matrix, to be considered in obtaining pharmaceutical and cosmetic preparations used in anti-aging strategies and, together with medications, in the management of age-related diseases. In further evaluations, the valuable functional properties of oak galls, reported mostly in preclinical studies, should be confirmed with clinical studies that would also take into account the potential health risks of their use.

Plant-Derived Nutraceuticals Involved in Body Weight Control by Modulating Gene Expression.

Obesity is the most prevalent health problem in the Western world, with pathological body weight gain associated with numerous co-morbidities that can be the main cause of death. There are several factors that can contribute to the development of obesity, such as diet, sedentary lifestyle, and genetic make-up. Genetic predispositions play an important role in obesity, but genetic variations alone cannot fully explain the explosion of obesity, which is why studies have turned to epigenetics. The latest scientific evidence suggests that both genetics and environmental factors contribute to the rise in obesity. Certain variables, such as diet and exercise, have the ability to alter gene expression without affecting the DNA sequence, a phenomenon known as epigenetics. Epigenetic changes are reversible, and reversibility makes these changes attractive targets for therapeutic interventions. While anti-obesity drugs have been proposed to this end in recent decades, their numerous side effects make them not very attractive. On the other hand, the use of nutraceuticals for weight loss is increasing, and studies have shown that some of these products, such as resveratrol, curcumin, epigallocatechin-3-gallate, ginger, capsaicin, and caffeine, can alter gene expression, restoring the normal epigenetic profile and aiding weight loss.

Antioxidants in Age-Related Diseases and Anti-Aging Strategies.

Aging is an intricate process and an important risk factor in the development and advancement of many disorders [...].

Walnut Intake Interventions Targeting Biomarkers of Metabolic Syndrome and Inflammation in Middle-Aged and Older Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Biomarkers of metabolic syndrome and inflammation are pathophysiological predictors and factors of senescence and age-related diseases. Recent evidence showed that particular diet components, such as walnuts rich in antioxidant bioactive compounds and with a balanced lipid profile, could have positive outcomes on human health. A systematic search in PubMed, EMBASE, Cochrane Library, Scopus, and ClinicalTrials.gov databases was performed to retrieve randomized controlled trials published from the beginning of each database through November 2021, reporting on the outcomes of walnut consumption over 22 metabolic syndrome and inflammatory markers in middle-aged and older adults. The search strategy rendered 17 studies in the final selection, including 11 crossover and 6 parallel trials. The study revealed that walnut-enriched diets had statistically significant decreasing effects for triglyceride, total cholesterol, and LDL cholesterol concentrations on some inflammatory markers and presented no consequences on anthropometric and glycemic parameters. Although further studies and better-designed ones are needed to strengthen these findings, the results emphasize the benefits of including walnuts in the dietary plans of this age group.

Protective Effects of Wine Polyphenols on Oxidative Stress and Hepatotoxicity Induced by Acrylamide in Rats.

In recent years, it has been increasingly suggested that the consumption of natural polyphenols, in moderate amounts, is beneficial for health. The aim of this study was to investigate the efficacy of a red wine (the administered dose of 7 mL/kg/day being equivalent to ~16.5 mg/kg/day total polyphenols) compared to a white wine (the administered dose of 7 mL/kg/day being equivalent to ~1.7 mg/kg/day total polyphenols), on the prevention of acrylamide-induced subacute hepatic injury and oxidative stress in Wistar rats. Hepatic damage due to acrylamide intoxication (the administered dose being 250 µg/kg body weight, for 28 days, by intragastric gavage) was assessed by employing biochemical parameters (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) and by histopathological studies. Markers of oxidative damage were measured in terms of plasma malondialdehyde (MDA), hepatic Thiobarbituric Acid Reactive Substances (TBARS) and glutathione (GSH) levels, and liver antioxidant enzyme (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)) activities. Regarding hepatic enzyme activities, treatment with red wine significantly decreased the AST values (p < 0.05), while for the ALT values only a normalization tendency was observed. Treatment with red wine and white wine, respectively, significantly prevented the increase in MDA and TBARS levels (p < 0.05), as well as the depletion of GSH (p < 0.05). Red wine treatment normalized the activities of the antioxidant enzymes CAT and SOD in rats intoxicated with acrylamide, while supplementing the diet with white wine did not produce significant differences in the antioxidant enzyme activities. Histopathological findings revealed a moderate protective effect of red wine after four weeks of daily consumption. Our findings provide evidence that red wine, having a higher phenolic content than white wine, has a significant protective effect on oxidative stress and liver injury induced by acrylamide in rats, through its antioxidative activity.

The Role of Vitamin K in Humans: Implication in Aging and Age-Associated Diseases.

As human life expectancy is rising, the incidence of age-associated diseases will also increase. Scientific evidence has revealed that healthy diets, including good fats, vitamins, minerals, or polyphenolics, could have antioxidant and anti-inflammatory activities, with antiaging effects. Recent studies demonstrated that vitamin K is a vital cofactor in activating several proteins, which act against age-related syndromes. Thus, vitamin K can carboxylate osteocalcin (a protein capable of transporting and fixing calcium in bone), activate matrix Gla protein (an inhibitor of vascular calcification and cardiovascular events) and carboxylate Gas6 protein (involved in brain physiology and a cognitive decline and neurodegenerative disease inhibitor). By improving insulin sensitivity, vitamin K lowers diabetes risk. It also exerts antiproliferative, proapoptotic, autophagic effects and has been associated with a reduced risk of cancer. Recent research shows that protein S, another vitamin K-dependent protein, can prevent the cytokine storm observed in COVID-19 cases. The reduced activation of protein S due to the pneumonia-induced vitamin K depletion was correlated with higher thrombogenicity and possibly fatal outcomes in COVID-19 patients. Our review aimed to present the latest scientific evidence about vitamin K and its role in preventing age-associated diseases and/or improving the effectiveness of medical treatments in mature adults ˃50 years old.

Enhanced Recovery of Phenolic and Tocopherolic Compounds from Walnut (Juglans Regia L.) Male Flowers Based on Process Optimization of Ultrasonic Assisted-Extraction: Phytochemical Profile and Biological Activities.

The extraction of bioactive compounds present in walnut (Juglans regia L.) male flowers (WMFs) was performed based on an experimental design using ultrasonic-assisted extraction. Solvent nature, extraction time, and water content were selected as experimental variables, and phenolic, flavonoidic, and condensed tannins contents and antioxidant properties were evaluated. Acetone was the solvent with the highest extraction performance, with the extracts obtained using this solvent displaying an increased concentration of bioactive compounds and increased antioxidant activities. For several extracts with high bioactive content, individual polyphenolic and tocopherolic compounds were evaluated by means of LC-MS and LC-MS/MS. The best extraction conditions for polyphenolic (2.86 mg gallic acid equivalents/g WMF) and tocopherolic compounds (29.4 µg/g WMF) were acetone with 40% water content (N20) and acetone with 20% water content (N15), respectively. Although the total tocopherol concentrations were lower than in other Juglans regia parts, most of the total tocopherol quantity was provided by the highly biologically active δ-tocopherol (84%). Significant quantities of quercetin (101.9 µg/g), hyperoside (2662.9 µg/g), quercitrin (405.7 µg/g), and isoquercitrin (1293.7 µg/g) were determined in WMF (N20). Both extracts inhibited the enzymatic activity of α-glucosidase and tyrosinase; however, an increased inhibition was observed for N20, the extract with the higher polyphenolic content. Conversely, N15 had higher anticancerous activity on the cell lines used, with a moderate selectivity towards the cancerous phenotype being observed for both extracts. At non-cytotoxic concentrations, both extracts displayed good antioxidant activities in cellular cultures, decreasing basal and H2O2-induced oxidative stress. This is the first characterization of both hydrophilic and lipophilic phytochemicals in WMF extracts. The outcomes of our study reveal that walnut male flowers have strong biological activities, thus justifying further research to demonstrate their usefulness in the food, pharmaceutical, and/or cosmetic industries.

Antitussive, Antioxidant, and Anti-Inflammatory Effects of a Walnut (Juglans regia L.) Septum Extract Rich in Bioactive Compounds.

The antitussive, antioxidant, and anti-inflammatory effects of a walnut (Juglans regia L.) septum extract (WSE), rich in bioactive compounds were investigated using the citric acid aerosol-induced cough experimental model in rodents. Wistar male rats were treated orally for three days with distilled water (control), codeine (reference), and WSE in graded doses. On the third day, all rats were exposed to citric acid aerosols, the number of coughs being recorded. Each animal was sacrificed after exposure, and blood and lung tissue samples were collected for histopathological analysis and the assessment of oxidative stress and inflammatory biomarkers. The results of the experiment showed a significant antitussive effect of WSE, superior to codeine. This activity could be due to cellular protective effect and anti-inflammatory effect via the stimulation of the antioxidant enzyme system and the decrease of IL-6 and CXC-R1 concentration in the lung tissue of WSE-treated animals. The antioxidant and anti-inflammatory effects of WSE were confirmed by biochemical assays and histopathological analysis. This is the first scientific study reporting the antitussive effect of walnut septum, a new potential source of non-opioid antitussive drug candidates, and a valuable bioactive by-product that could be used in the treatment of respiratory diseases.

A comparison of a ketogenic diet with a LowGI/nutrigenetic diet over 6 months for weight loss and 18-month follow-up.

BACKGROUND: Obesity and its related metabolic disturbances represent a huge health burden on society. Many different weight loss interventions have been trialled with mixed efficacy, as demonstrated by the large number of individuals who regain weight upon completion of such interventions. There is evidence that the provision of genetic information may enhance long-term weight loss, either by increasing dietary adherence or through underlying biological mechanisms. METHODS: The investigators followed 114 overweight and obese subjects from a weight loss clinic in a 2-stage process. 1) A 24-week dietary intervention. The subjects self-selected whether to follow a standardized ketogenic diet (n = 53), or a personalised low-glycemic index (GI) nutrigenetic diet utilising information from 28 single nucleotide polymorphisms (n = 61). 2) After the 24-week diet period, the subjects were monitored for an additional 18 months using standard guidelines for the Keto group vs standard guidelines modified by nutrigenetic advice for the low-Glycaemic Index nutrigenetic diet (lowGI/NG) group. RESULTS: After 24 weeks, the keto group lost more weight: - 26.2 ± 3.1 kg vs - 23.5 ± 6.4 kg (p = 0.0061). However, at 18-month follow up, the subjects in the low-GI nutrigenetic diet had lost significantly more weight (- 27.5 ± 8.9 kg) than those in the ketogenic diet who had regained some weight (- 19.4 ± 5.0 kg) (p < 0.0001). Additionally, after the 24-week diet and 18-month follow up the low-GI nutrigenetic diet group had significantly greater (p < 0.0001) improvements in total cholesterol (ketogenic - 35.4 ± 32.2 mg/dl; low-GI nutrigenetic - 52.5 ± 24.3 mg/dl), HDL cholesterol (ketogenic + 4.7 ± 4.5 mg/dl; low-GI nutrigenetic + 11.9 ± 4.1 mg/dl), and fasting glucose (ketogenic - 13.7 ± 8.4 mg/dl; low-GI nutrigenetic - 24.7 ± 7.4 mg/dl). CONCLUSIONS: These findings demonstrate that the ketogenic group experienced enhanced weight loss during the 24-week dietary intervention. However, at 18-month follow up, the personalised nutrition group (lowGI/NG) lost significantly more weight and experienced significantly greater improvements in measures of cholesterol and blood glucose. This suggests that personalising nutrition has the potential to enhance long-term weight loss and changes in cardiometabolic parameters. TRIAL REGISTRATION: NCT04330209, Registered 01/04/2020, retrospectively registered.