ABSTRACT

Emerging evidence suggests dietary interventions regulate inflammatory signaling through gut microbiome modulation, yet their therapeutic potential in radiation-induced intestinal injury (RIII)remains underexplored. This study demonstrates that the ketogenic diet (KD), a high-fat and low-carbohydrate dietary regimen, exerts protective effects against RIII through dual mechanisms involving microbial regulation and inflammatory pathway inhibition. Using high-salt diet (HSD) as a dietary control,KD significantly attenuated intestinal inflammation by downregulating pro-inflammatory cytokines while enhancing barrier integrity through tight junction protein upregulation in a radiation-exposed murine model.16S rDNA sequencing showed KD enriched Akkermansia and reduced Enterobacteriaceae, whereas HSD exhibited inverse patterns. Mechanistically, RNA sequencing revealed that KD uniquely suppressed theJAK2/STAT3 pathway in RIII mice. In vitro studies demonstrated that β-hydroxybutyrate, a key ketone metabolite, effectively suppressed RORγt expression and subsequent downregulation of IL-17A gene transcription via the inhibition of JAK2/STAT3 pathway, thus mitigate inflammatory damage. Fecal microbiota transplantation validated that KD-modified microbiome directly inhibited JAK2/STAT3signaling activation, as well as the downregulation of RORγt and IL-17A. These findings establish KD as a promising dietary strategy mitigate acute RIII through synergistic modulation of gut microbiota and inflammatory signaling, providing novel insights into nutritional approaches targeting microbial-hostcrosstalk in radiation injury.

Yang, Jingjing, Zhi Ling, Ming Zhou, Mingyang Tao, Jingxian Mao, Huaijuan Guo, Jiaxin Wang et al. "Ketogenic diet alleviates acute radiation-induced intestinal injury through JAK2/STAT3/RORγt/IL-17A signaling pathway via gut microbiome." Communications Biology (2026).

https://www.nature.com/articles/s42003-026-10546-9_reference.pdf

Abstract

Purpose

This systematic review aimed to synthesize current evidence on the effects of various dietary interventions on anthropometric, metabolic, hormonal, inflammatory, and oxidative stress parameters in women with polycystic ovary syndrome (PCOS).

Methods

The review followed the PRISMA guidelines and was prospectively registered in PROSPERO (CRD42025641781). Searches were conducted in PubMed, Cochrane Library, EBSCO, Science Direct, Web of Science, National Thesis Center, Google Scholar, and DergiPark Academic for studies published between February 2015 and February 2025. Experimental and observational studies were included if they evaluated the independent effect of dietary interventions in adult women with PCOS. Methodological quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools.

Results

A total of 38 studies were included, covering interventions such as calorie-restricted diets, low-glycemic index/load diets, ketogenic diets, intermittent fasting, dietary approaches to stop hypertension, Mediterranean-style, and other diets. Most dietary interventions demonstrated beneficial effects on body weight, body mass index, and waist circumference, as well as improvements in insulin sensitivity, reproductive hormone regulation, and menstrual regularity. However, findings related to lipid metabolism, inflammatory markers, and oxidative stress outcomes were inconsistent.

Conclusion

Current evidence indicates that dietary interventions are crucial in improving the management of metabolic, anthropometric, hormonal, and clinical outcomes in women with PCOS. Nevertheless, the heterogeneity of dietary approaches, study designs, and outcome measures highlights the need for long-term randomized controlled trials to establish more conclusive recommendations.

Akbaş, Elif, Merve Samancı, and Yasemin Ertaş Öztürk. "Nutrition interventions in women with polycystic ovary syndrome: a systematic review." European Journal of Nutrition 65, no. 5 (2026): 176.

https://link.springer.com/content/pdf/10.1007/s00394-026-04030-7.pdf

ABSTRACT

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by both motor and non-motor symptoms that significantly impair patients' quality of life. While pharmacological therapies provide symptomatic relief, no disease-modifying treatments have been conclusively established. In recent years, there has been increasing interest in non-pharmacological interventions, including dietary strategies, for their potential role in symptom management and disease modification. This literature review aims to examine the emerging role of the ketogenic diet (KD) in the management of PD, exploring its potential to alleviate symptoms and impact disease progression. Preliminary evidence suggests that KD may offer symptomatic benefits in PD through mechanisms such as mitochondrial support, anti-inflammatory effects, neuroinflammation, and impacting gut dysbiosis. Studies have shown promising results, particularly for non-motor symptoms such as urinary function, fatigue and cognition, however consistent improvement in motor outcomes has yet to be demonstrated. It should be noted that existing clinical data are derived from small pilot trials (generally n<20) with heterogenous dietary protocols and variable ketone targets, limiting definitive conclusions. While the mechanistic rational and early clinical signals are encouraging, larger and longer duration randomized controlled trials with standardized ketogenic protocols are needed to fully characterize KD’s potential in PD management.

Hitawala, Gazala, and Lisa M. Shulman. "A Fat Chance at Neuroprotection: Ketogenic Diet and Parkinson’s Disease." Clinical Nutrition ESPEN (2026): 103430. https://doi.org/10.1016/j.clnesp.2026.103430

https://www.sciencedirect.com/science/article/abs/pii/S2405457726005279

Abstract

Introduction.Currently, metabolic syndrome is manifested by symptoms such as obesity, weight gain and excess fat accumulation among the population, which, as a result, is manifested by diseases such as diabetes mellitus and insulin resistance among the population. According to the World Health Organization, the number of diabetes mellitus patients currently exceeds 400 million worldwide. In 2019 alone, diabetes ranked ninth in terms of causes of death, leading to approximately 1.5 million deaths. The prevalence of obesity and diabetes has reached pandemic levels over the past 50 years, which in turn leads to the development of metabolic syndrome in the body and dysfunction of all organs and tissues of the body, including lung tissue. This disease, as a result of the accumulation of hypoxic cells around organs and tissues, causes respiratory diseases such as pneumonia, bronchial asthma, pulmonary hypertension, acute respiratory distress syndrome (ARDS) and obstructive sleep apnea syndrome, disruption of lung homeostasis and the immune system, and changes in the population of inflammatory cells in the lung in obesity have been studied by a number of foreign researchers. Scientists from the CIS countries have elucidated the complex pathophysiological mechanisms of obesity and diabetes, the presence of mitochondrial dysfunction, endoplasmic reticulum stress in this process, and the mechanisms of changes in cellular and intracellular redox balance. In our country, few studies have been conducted on non-respiratory lung functiondisorders in metabolic syndrome, their early diagnosis, and correction of identified changes. For this reason, the implementation of this scientific research is of scientific and practical importance.

Research objective: To observe the effect of a traditional and modified ketogenic diet on non-respiratory lung functions in metabolic syndrome and analyze the results obtained.Material and research methods:To achieve the goal of the study, rats were given a high-fat, low-carbohydrate diet and a glucose-fructose mixture instead of water for 2 months, and metabolic syndrome was modeled. Starting from 3 months, they were divided into groups and a traditional and modified ketogenic diet was used for 1 month. Biochemical tests were performed on the blood.

Results:It is important to study the changes in the levels of alpha-1 antitrypsin, myeloperoxidase, and surfactant protein in the blood serum to monitor changes in the lungs during the diet used in metabolic syndrome. It was found that body weight and alpha-1 antitrypsin levels increased in rats modeled with metabolic syndrome compared to intact rats. In particular, it was found that alpha-1 antitrypsin levels in the blood plasma of rats modeled with metabolic syndrome increased by 1.28; 1.38 and 1.68 times compared to the intact group at 1; 2 and 3 months, respectively. The reason for such changes in the blood is that alpha-1 antitrypsin increases in the amount of metabolism in the lungs, when inflammatory processes increase.In such disorders, an imbalance is observed in the non-respiratory functions of the lungs and the amount of substances produced in it. In the groups of rats treated with a modified ketogenic diet, it was found that the amount of alpha-1 antitrypsin decreased compared to the conventional and diseased groups, and this indicator was close to that of healthy rats. In particular, in the group treated with a modified ketogenic diet, it decreased by 25.8%, and in the group treated with a conventional ketogenic diet, it decreased by 18.2%. This indicates that the modified diet used has a more effective effect compared to the conventional ketogenic diet.

Conclusion. The results obtained indicate that the amount of alpha-1 antitrypsin increases as a result of structural and functional impairment of the lungs in metabolic syndrome. The use of a modified ketogenic diet effectively affected the morphology and non-respiratory functions of the lungs.

Sh, Rabimova Z., D. M. Azizova, and Inoyatova F. Kh. "DEVELOPMENT OF HYPERCHOLESTERINEMIA IN METABOLIC SYNDROME AND ITS CORRECTION." GERMANY-SCIENTIFIC REVIEW OF THE PROBLEMS AND PROSPECTS OF MODERN SCIENCE AND EDUCATION 1, no. 16 (2026): 11-12.

https://e-conferences.org/index.php/Germany/article/view/1280

Abstract

Proposed mechanism of the ketogenic diet-microbiota-MMA-immune axis in CRC. (Part 1) A ketogenic diet remodels gut microbiota homeostasis by depleting MMA-producing bacteria, thereby reducing the accumulation of the oncometabolite (MMA). (Part 2) At the molecular level, MMA acts as a ligand that binds to Rap1, activating the downstream MAPK/ERK signalling cascade. This signalling event drives the transcriptional reprogramming of TAMs towards the pro-tumorigenic M2 phenotype. (Part 3) Clinically, elevated serum MMA in CRC patients correlates with increased M2 macrophage infiltration in the tumour microenvironment and poor prognosis.

Lu, Yang, Bo Shi, Jinmiao Chen, Huihui Yao, Xiuwei Mi, Minke Shao, Yiyuan Zhao et al. "Ketogenic Diet Alleviates Colorectal Cancer by Attenuating Macrophage M2 Polarisation Triggered by Oncometabolite MMA Derived From the Gut Microbiota." Cell proliferation: e70247.

https://onlinelibrary.wiley.com/doi/10.1111/cpr.70247

ABSTRACT

Objective: This study assessed changes in body composition and 24-h energy metabolism at 6 and 12 months after initiation of a 1-month very low-calorie ketogenic diet (VLCKD) in women with obesity.

Methods: Seventeen women with obesity who completed a 1-month VLCKD underwent a 4-week transition phase with carbohydrate reintroduction, followed by a hypocaloric balanced diet. Assessments of body composition by dual-energy X-ray absorptiometry (DXA) and 24-h energy expenditure (24hEE) by a whole-room indirect calorimeter were performed.

Results: Following the initial 7% weight loss, body weight further decreased at 6 months (−3.9%, p < 0.05), primarily driven by a significant decrease in fat mass (−10%, p < 0.05). From 6 to 12 months, three participants continued to lose weight, whereas most remained stable or partially regained. Lean soft tissue, decreased during the VLCKD phase, remained stable throughout follow-up. Both 24hEE and 24-h sleeping metabolic rate exhibited a progressive trend toward increase. Minute- by-minute 24hEE trajectories revealed a significant increase in metabolic rate from 1 to 6 months (p < 0.001). The metabolic adaptation observed after 1 month of VLCKD was no longer detectable at either 6 or 12 months.

Conclusions: These findings provide novel insight into the physiological adaptations following VLCKD, supporting its role in supervised weight loss programs for selected patients.

Trial Registration: ClinicalTrials.gov identifier: NCT07418281

Basolo, A., Piaggi, P., Angeli, V., Fierabracci, P., Bologna, C., Paolucci, G., Salvetti, G., Chiovato, L., Krakoff, J., Landi, A., & Santini, F. Six- and Twelve-Month Changes in Body Composition and 24-h Energy Expenditure After a Very Low-Calorie Ketogenic Diet. Obesity. https://doi.org/10.1002/oby.70236

https://onlinelibrary.wiley.com/doi/pdf/10.1002/oby.70236

Abstract

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), particularly semaglutide, have demonstrated efficacy for weight loss in obesity; however, up to 40% of weight lost may derive from lean body mass. The ketogenic diet independently improves insulin sensitivity and promotes fat oxidation while preserving lean tissue. This study aimed to describe changes in body composition, insulin sensitivity, and cardiometabolic markers in patients who followed a personalized ketogenic dietary protocol while receiving low-dose semaglutide over a 6-month insulin resistance reversal program. Methods: Seven analyzed adults (six female, one male) with overweight or obesity (baseline BMI 25.6–47.2 kg/m^(2)) participated in a clinician-supervised 6-month program combining a whole-food ketogenic diet with semaglutide (≤1.0 mg/week). Body composition and fasting metabolic markers were assessed at 1, 3, and 6 months. Results: Mean total weight loss was 21.9 kg, of which a mean of 92% was attributable to BIA-estimated fat mass. Skeletal muscle mass was largely preserved as measured by BIA (mean loss 1.2 kg), and one patient gained lean tissue. Fasting insulin declined by a mean of 15.6 µIU/mL. Visceral fat decreased by a mean of 37.0%. Six of seven patients showed reductions in high-sensitivity C-reactive protein. Triglycerides decreased in six of seven patients, and HDL cholesterol increased in all seven. LDL cholesterol responses were heterogeneous. Conclusions: In this small, uncontrolled case series, combining a ketogenic diet with low-dose semaglutide was associated with substantial fat loss, apparent preservation of lean mass as measured by BIA, and improvements in insulin sensitivity and cardiometabolic markers. Because the semaglutide dose and dietary protocol were individualized to each patient’s response, the program illustrates a personalized approach to insulin resistance. These preliminary findings are hypothesis-generating and warrant confirmation in controlled prospective studies.

Parker, Genevieve, Madeline D. Morris, Jeter R. Heggie, Ella F. Cooper-Leavitt, Cameron J. Clark, Asher P. Reynolds, Holly A. Smith et al. "Personalized Combination of a Ketogenic Diet and Low-Dose Semaglutide for Cardiometabolic Health: A Retrospective Case Series." Journal of Personalized Medicine 16, no. 6 (2026): 313.

https://www.mdpi.com/2075-4426/16/6/313

Abstract

Purpose

To assess whether the Ketogenic Diet (KD) is associated with improvements in biochemical markers of hyperandrogenism in women diagnosed with Polycystic Ovary Syndrome (PCOS) with obesity or overweight.

Methods

A systematic search was conducted in five databases: MEDLINE (via PubMed), Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and Web of Science. Both RCTs and pre-post studies providing data for direct extraction or calculation of mean (SD) changes in the investigated outcomes, published until March 1, 2025, were considered. Protocols included “Very Low” and “Low” Calories KD, and modified KD regimens. The primary outcome was the effect of the KD on total testosterone (TT), Free T (FT) and Sex Hormone Binding Globulin (SHBG) compared to baseline.

Results

The KD was found to be associated with a statistically significant reduction in TT (n = 290, Mean Difference [MD] -0.35, CI -0.46; -0.24) and a significant increase in SHBG levels (n = 144, MD 19.50, CI 6.90; 32.11), independently of study design. When considering only RCTs (4 studies), the KD showed a moderate, statistically significant benefit on TT levels compared to the control intervention, with a high heterogeneity (n = 115 vs. 117, SMD -0.284, CI -0.543, -0.035; p = 0.031). Neither the duration of the KD protocol, the change in BMI, the change in fasting insulin levels nor the change in LH/FSH ratio were able to significantly affect the change in TT levels observed over time. In addition, the KD associated with a significant reduction in LH levels (n = 275, MD -3.48, CI -4.71; -2.26) and in the LH/FSH ratio (n = 275, MD -0.99, CI -1.44; -0.54).

Conclusion

Our meta-analysis indicates a reduced biochemical hyperandrogenism—particularly a reduction in TT—and a reduction in the LH/FSH ratio among women with PCOS following a KD. Our findings also suggest a specific effect of ketosis on ovarian function acting alongside metabolic improvements, but a direct causal link cannot be definitively established. Owing to the low quality and heterogeneous nature of the available studies, larger, high-quality RCTs are essential to consolidate this evidence and determine clinical efficacy.

Maseroli, E., Alfaroli, C., Cirillo, M. et al. Ketogenic diet as a therapeutic intervention for biochemical hyperandrogenism in PCOS women with obesity or overweight: a meta-analytic study. J Endocrinol Invest (2026). https://doi.org/10.1007/s40618-026-02924-1

https://link.springer.com/article/10.1007/s40618-026-02924-1

ABSTRACT

The ketogenic diet (KD), characterized by a high-fat, moderate-protein, and low-carbohydrate macronutrient composition, has gained growing interest as a potential nutritional approach to cardiometabolic diseases and aging. Emerging evidence suggests that ketone bodies, particularly β-hydroxybutyrate, act not only as alternative energy substrates but also as signaling molecules that influence vascular, metabolic, and epigenetic pathways. This review summarizes current knowledge on the cardiovascular and metabolic implications of KD, emphasizing endothelial function, cardiac energy metabolism, lipid profile, and blood pressure regulation. Experimental and clinical data indicate that KD enhances endothelial antioxidant capacity via Nrf2 activation and eNOS upregulation, reduces cellular senescence, and modulates epigenetic regulators such as histone β-hydroxybutyrylation and SIRT1. In heart failure, acute ketone supplementation improves cardiac output and energetics, while chronic adherence to KD may impair hepatic ketogenesis and lipid homeostasis, potentially offsetting its benefits. Evidence in hypertension and dyslipidemia remains controversial, with short-term improvements often contrasted by long-term elevations in LDL cholesterol and arterial stiffness. In patients with type 2 diabetes, KD promotes glycemic control and insulin sensitivity, yet the sustainability and cardiovascular safety of prolonged use are uncertain. Overall, KD represents a promising but complex therapeutic tool whose efficacy depends on individual metabolic context, diet composition, and duration. A balanced, intermittent, or cyclic ketogenic approach may offer a safer strategy to harness its cardiometabolic and anti-aging benefits.

Cioffi, Giuseppe, Gianluigi Cuomo, Raffaele Carluccio, Crescenzo Testa, Anna Di Lorenzo, Luigi De Vito, Valentina Parisi, Maddalena Conte, Dario Leosco, and Francesco Giallauria. "Ketogenic diet, cardiometabolic diseases and aging." Journal of Geriatric Cardiology 23, no. 5 (2026): 275-283.

http://jgc301.com/en/article/pdf/preview/10.26599/1671-5411.2026.05.005.pdf

Abstract

Background: For individuals living with Parkinson’s disease (PD), the earliest and most disruptive changes are often not tremor or rigidity, but a gradual loss of mental clarity, physical confidence and social ease that reshapes everyday life.
Aim: To explore how individuals with PD described changes in mental, physical and social quality of life (QoL) before and after participating in a 12-week low-carbohydrate, healthy-fat ketogenic dietary intervention.
Setting: The study setting consisted of participants recruited through the Colorado Parkinson Foundation, a community-based organisation supporting individuals living with Parkinson’s disease and their caregivers. All participants resided in the United States during the study period.
Methods: Sixteen adults diagnosed with PD, aged 36–81 years, participated in this descriptive phenomenological study. Participants were recruited with assistance from the Colorado Parkinson Foundation and resided in the United States. Semi-structured interviews were conducted via Zoom before and after the dietary intervention to capture participants’ lived experiences across time.
Results: Pre-study interviews yielded three major themes describing participants’ experiences prior to dietary change, while post-study interviews yielded four major themes reflecting experiences following completion of the intervention. Participants described changes related to mental clarity, physical function, social engagement, metabolic health and relational support.
Conclusion: Findings highlight how metabolic-based dietary intervention was experienced in everyday life by individuals living with PD. Participants described improvements in mental clarity, physical function and social engagement that corresponded to observed changes in metabolic health, suggesting a meaningful connection between metabolic adaptation and QoL.
Contribution: Centring participant perspectives provides important patient-centred insight into how metabolic changes associated with a ketogenic diet (KD) intervention are experienced and integrated into QoL beyond clinical or biomarker outcomes.

White, Dawn R., Tim A. White, and Melanie M. Tidman. "How the ketogenic diet affects patients with Parkinson’s disease: A descriptive phenomenological study." Journal of Metabolic Health 9, no. 1 (2026): 10. DOI: https://doi.org/10.4102/jmh.v9i1.144

https://journalofmetabolichealth.org/index.php/jmh/article/view/144

Abstract

Background: For individuals living with Parkinson’s disease (PD), the earliest and most disruptive changes are often not tremor or rigidity, but a gradual loss of mental clarity, physical confidence and social ease that reshapes everyday life.
Aim: To explore how individuals with PD described changes in mental, physical and social quality of life (QoL) before and after participating in a 12-week low-carbohydrate, healthy-fat ketogenic dietary intervention.
Setting: The study setting consisted of participants recruited through the Colorado Parkinson Foundation, a community-based organisation supporting individuals living with Parkinson’s disease and their caregivers. All participants resided in the United States during the study period.
Methods: Sixteen adults diagnosed with PD, aged 36–81 years, participated in this descriptive phenomenological study. Participants were recruited with assistance from the Colorado Parkinson Foundation and resided in the United States. Semi-structured interviews were conducted via Zoom before and after the dietary intervention to capture participants’ lived experiences across time.
Results: Pre-study interviews yielded three major themes describing participants’ experiences prior to dietary change, while post-study interviews yielded four major themes reflecting experiences following completion of the intervention. Participants described changes related to mental clarity, physical function, social engagement, metabolic health and relational support.
Conclusion: Findings highlight how metabolic-based dietary intervention was experienced in everyday life by individuals living with PD. Participants described improvements in mental clarity, physical function and social engagement that corresponded to observed changes in metabolic health, suggesting a meaningful connection between metabolic adaptation and QoL.
Contribution: Centring participant perspectives provides important patient-centred insight into how metabolic changes associated with a ketogenic diet (KD) intervention are experienced and integrated into QoL beyond clinical or biomarker outcomes.

White, Dawn R., Tim A. White, and Melanie M. Tidman. "How the ketogenic diet affects patients with Parkinson’s disease: A descriptive phenomenological study." Journal of Metabolic Health 9, no. 1 (2026): 10. DOI: https://doi.org/10.4102/jmh.v9i1.144

https://journalofmetabolichealth.org/index.php/jmh/article/view/144

Abstract

Traumatic brain injury (TBI) affects millions globally each year, often resulting in long-term health issues or death. While the immediate physical damage caused by these injuries receives much attention, subsequent metabolic changes in the brain are equally vital to recovery but understudied. After TBI, brain energy regulation and consequential metabolic processes are disrupted. This review provides a detailed examination of metabolic alterations following TBI, including glucose and lipid processing disruptions, increased lactate levels, neurotransmitter imbalances, and oxidative stress. These changes can lead to hyper/hypoglycemia, lactate accumulation, chemical imbalances, and heightened oxidative stress, all of which impede recovery. Understanding these biochemical shifts is essential for developing more effective treatments. This review offers a comprehensive overview of brain metabolic changes post-TBI and discusses some promising therapies, including drugs, nutrition, and lifestyle adjustments, that could aid recovery and improve the quality of life of those impacted.

Ali, A., Hussain, M. S., Ahmed, M. E., Giri, S., & Ahmad, A. S. Metabolic Dysregulation in Traumatic Brain Injury: Mechanisms, Clinical Implications, and Therapeutic Opportunities. Journal of Neurotrauma. https://doi.org/10.1177_08977151261452922

https://journals.sagepub.com/doi/abs/10.1177/08977151261452922

Abstract

Physical exercise and nutritional strategies have become powerful tools for improving brain health, boosting cognitive performance, slowing cognitive decline, and reducing the risk of neurodegenerative diseases, primarily by influencing neurotrophic factors such as brain-derived neurotrophic factor (BDNF). This review examines the impact of various exercise types (endurance, high-intensity interval training, and resistance) along with dietary approaches (ketogenic diet and intermittent fasting) on BDNF, with a focus on their potential to promote cognition and neuroprotective benefits, particularly in the middle-aged and older population. Several molecular and physiological pathways may be involved, including activation of the PGC1 alpha-FNDC5-BDNF pathway, lactate signaling, increased blood flow to the brain and body, splenic platelet release, and stimulation of TrkB, IGF-1, irisin, and cathepsin B. Nutritional interventions may also boost BDNF through mechanisms involving beta-HB and Notch 1 signaling. Research from both animal and human studies highlights the potential benefits of exercise and dietary modifications in supporting brain health and cognitive function. However, differences in study design and methodological limitations make it difficult to draw firm conclusions. These effects appear to be influenced by factors such as exercise characteristics (intensity, modality, and duration), the timing of blood collection, and the type of cognitive assessments. Future studies should focus on identifying the most effective intervention protocols and mechanisms, as well as understanding the individual factors that influence responsiveness to neurotrophic changes. Overall, targeted exercise and dietary strategies offer a promising approach to maintain brain health and reduce cognitive decline associated with aging and disease.

Givralli, Jacopo, Tatiana Moro, Tõnis Timmusk, and Antonio Paoli. "The Interplay Between Physical Exercise, Nutritional Strategies, and Brain-Derived Neurotrophic Factor in Promoting Cognitive Performance." Aging and Disease (2026).

https://www.research.unipd.it/bitstream/11577/3597303/1/The%20Interplay%20Between%20Physical%20Exercise%2C%20Nutritional%20Strategies%2C%20and%20Brain-Derived%20Neurotrophic%20Factor%20in%20Promoting%20Cognitive%20Performance.pdf

ABSTRACT

Alzheimer’s disease (AD) is a progressive, irreversible neurodegenerative disorder and a major health alarm worldwide, characterized by cognitive decline, neuronal dysfunction, and memory impairment. The relevance of nutrition toward AD is limited; therefore, this review explores how nutrition may help prevent cognitive decline in the early stages of AD, emphasizing dietary patterns and key nutrients. Early diagnosis is crucial, as numerous complications characterize the later stages. The current therapeutics can only suppress the progression; therefore, nutrition-based therapeutic approaches have emerged as an alternate and pivotal strategy to mitigate cognitive decline in early-stage AD patients. The disease has complex pathology; therefore, early diagnosis and the role of biomarkers are very important and warrant further exploration. Although there is no specific diet that could prevent or cure AD, an increasing number of studies show that nutrition plays an important role in maintaining the function of the brain and slowing neurodegeneration. Consequently, switching to a healthy diet along with a better lifestyle may contribute to the prevention of neurodegeneration and reduce the risk of AD in the future. Therefore, this review highlights the dietary patterns and key nutrients that may help prevent or minimize the impact of AD. Additionally, it examines case studies and explores future research directions, thereby emphasizing the role of a healthy diet as a complementary therapeutic approach.

Noori, Hamid, Kayla Dixon, Sana Aqil Khan, Krutika Mahendra Gohil, Arghadip Das, Shahpoor Ahmad Shirzada, Mohammed Elmujtba Adam Essa Adam, and Saurav Kumar Mishra. "Nutritional interventions to managing cognitive decline in early Alzheimer's disease." Nutrition clinique et métabolisme 40, no. 3 (2026): 103047.

https://www.sciencedirect.com/science/article/pii/S098505622600018X

Objective:

Ketogenic diets (KD) are effective tools for weight loss and cardiometabolic risk reduction. Evidence suggests that very-low-energy ketogenic diets can reduce blood pressure (BP) by approximately 7–8/6–7 mmHg. These effects may be weight-independent, potentially mediated by improved endothelial function and the anti-inflammatory properties of ketone bodies. However, real-world clinical data remain limited. This study evaluated the impact of a low-energy ketogenic diet (LEKD) on Blood Pressure, arterial stiffness, and endothelial function in adults with obesity.

Design and method:

A total of 27 adults with obesity were enrolled in a 12-week LEKD protocol. Office Blood pressure was monitored. Arterial stiffness was assessed via Pulse Wave Velocity (PWV), while endothelial function was measured through Flow-Mediated Dilatation (FMD). Body composition and metabolic markers were tracked throughout the intervention.

Results:

The LEKD intervention resulted in a significant reduction in systolic (126.4 ± 9.8 mmHg to 118.2 ± 10.4 mmHg, a reduction of 8.2 mmHg, p = 0.050) and diastolic (79.5 ± 9.6 to 70.4 ± 5.1 mmHg, a reduction of 9.2 mmHg, p = 0.010) blood pressure.

We observed a clinically meaningful improvement in arterial stiffness, with PWV decreasing. Endothelial function showed a marked enhancement (FMD: +2.6%).

Notably, these cardiovascular improvements were only partially correlated with the total weight loss (97.9 ± 18.7 to 86.3 ± 17.4 kg, a reduction of 11.6 kg, p < 0.001), suggesting a direct metabolic effect of nutritional ketosis.

Conclusions:

LEKD effectively reduces office blood pressure and improves vascular function in patients with obesity. The observed enhancements in arterial stiffness and endothelial function support the role of nutritional ketosis as a vasoprotective strategy that extends beyond the benefits of weight reduction alone. These findings highlight LEKD as a potent clinical tool for cardiovascular risk management.

Carducci, Augusto, Pierfrancesco Di Matteo, Giulia Ferrovecchio, Federica Pingiotti, Claudio Ferri, and Davide Grassi. "EFFECTS OF LOW ENERGY KETOGENIC DIET ON BLOOD PRESSURE, ARTERIAL STIFFNESS AND ENDOTHELIAL FUNCTION: A PROSPECTIVE INTERVENTIONAL STUDY." Journal of Hypertension 44, no. Suppl 1 (2026): e117.

https://journals.lww.com/jhypertension/fulltext/2026/04001/effects_of_low_energy_ketogenic_diet_on_blood.373.aspx

Introduction: F-18 FDG requires significant dietary preparation to fully suppress myocardial glucose metabolism and reveal inflammatory processes, such as sarcoidosis or myocarditis. The relationship between higher beta-hydroxybutyrate (BHB) levels and myocardial glucose suppression (MGS) has been well established: higher the BHB levels associate with greater MGS and improved diagnostic confidence.1 Some facilities collect a blood sample on the day of the exam and use its results afterward to confirm their reports. A recent publication suggests that a threshold of ≥0.35 mmol/L is appropriate for predicting diagnostic image quality, whereas others suggest ≥0.5 mmol/L.1,2 Recently, point-of-care (POC) systems have gained popularity since they can be used before the exam to confirm the patient’s reported compliance with the diet preparation. While there is a comparison between lab BHB and POC BHB in healthy children3, to our knowledge, there has not been a comparison of the two for BHB levels and resulting ^(18)FDG cardiac image quality.

Methods: 9 inpatients were prepped with a 3-day ketogenic diet and 12 hours of fasting. The floor drew inpatient BHB labs before the exam, and point-of-care ketones (Precision Xtra, Abbott ADC-84880 v2.0) were tested upon the patient’s arrival in the PET department. Inpatient labs were drawn after midnight or in the early morning hours when the fasting time was shorter.

Results: 40% (4/9) of patients were diabetic or had a diagnosis of CKD, posing a higher risk of developing ketoacidosis and inducing kidney injury during a ketogenic diet preparation. Point-of-care meter results were significantly higher than the lab-drawn test, with a mean of 1.3 mmol/L versus 0.7 mmol/L (P = 0.046) and a mean difference of 0.6 mmol/L; one measurement fell outside the upper bounds of the Bland-Altman comparison in Figure 1. The average time between tests was 7.6 hours. 8 of the 9 had diagnostic quality exams (89%).One diabetic patient fell into ketoacidosis levels (>4 mmol/L) by the POC system. Another patient had diffuse-focal uptake in the basal-lateral wall, more intense than the liver, without any visible ^(18)FDG blood pool, and lower BHB levels (0.23 lab and 0.4 POC). This exam was repeated after 2 additional days of ketogenic diet preparation to rule out this non-specific uptake (Figure 2). The BHB rose to 0.54 by the lab and 1.4 by POC, respectively. The basal-lateral myocardial uptake is now less intense, allowing for better visualization of active pulmonary and mediastinal lymph nodes, and was read as likely non-specific myocardial uptake. In this case of non-specific uptake, MGS is not complete with BHB > 0.5 (higher than any previously proposed threshold).

Conclusions: Point-of-care testing for beta-hydroxybutyrate after dietary preparation for cardiac sarcoid imaging systematically exceeded inpatient lab testing, albeit about 8 hours later. Even high BHB levels >0.5 do not exclude non-specific myocardial FDG uptake.

https://jnm.snmjournals.org/content/67/supplement_1/26163.abstract

Roby, Amanda, Kenneth lance Gould, Nils Johnson, Lindsey Harmon, and Kelly Sander. "Point-of-care ketone testing compared with hospital lab testing to assess the quality of diet preparation for cardiac inflammation imaging using positron emission tomography." (2026): 26163-26163.

ABSTRACT

Emerging evidence suggests the therapeutic potential of ketogenic diet (KD) for mood disorders such as depression, yet the underlying mechanisms are poorly understood. Here we report a gut microbe-to-brain signaling pathway through which KD protects against depressive-like behavior in mice. We show that KD feeding triggers a prompt and dynamic remodeling of the gut microbiome, the depletion of which abrogates the protective effect of KD against depressive-like behavior in stressed mice. Colonization with Roseburia intestinalis (R. intestinalis), which is enriched by 1-week KD, sustains the protective effect of KD against depressive-like behavior in mice. The protective effect of KD is linked to the reduction of a host-microbe co-metabolite p-Cresol sulfate (p-CS), the supplementation of which negates the protective effect of KD against depressive-like behavior. Mechanistically, p-CS enters the brain and activates lateral habenula (LHb) to counteract the protective effect of KD. Our findings uncover a gut microbiota-brain axis mechanism for KD consumption to protect against depressive-like behavior.

Zhang, Youying, Xuanyao Li, Xuanshuang Zhang, Ying Wang, Zixin Chen, Xuan Lin, Xiao Zheng, Haiping Hao, and Xueli Zhang. "Ketogenic Diet Modulates Depressive‐Like Behavior via Gut Bacterial Metabolism of Tyrosine." The FASEB Journal 40, no. 10 (2026): e71966.

https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.202504666RRR

Abstract

The ketogenic diet (KD) is increasingly recognized as a promising therapeutic strategy for neurodegenerative disorders because of its multifaceted impacts on key pathophysiological mechanisms. This review explores the molecular pathways through which KD may protect against neurodegeneration, including the use of ketone bodies as alternative energy substrates, reduction of oxidative stress and inflammation, modulation of autophagy and protein aggregation, and impact on the gut microbiome. The potential benefits of KD are explored across neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and multiple sclerosis, based on both preclinical and clinical evidence that supports its feasibility. However, challenges in long-term safety, patient adherence, and clinical practicality limit its widespread adoption. This review underscores the potential of KD for treating neurodegeneration on the basis of current scientific evidence while highlighting the need for further research to optimize its application and address existing gaps.

Salgueiro, Ana Margarida, Marisa Ferreira-Marques, Rodrigo FN Ribeiro, Sara M. Lopes, Dina Pereira, Daniela G. Costa, Magda M. Santana, Luís Pereira de Almeida, and Cláudia Cavadas. "Ketogenic diet as a therapeutic strategy for neurodegenerative diseases: from mechanisms to translational challenges." Translational Neurodegeneration 15, no. 1 (2026): 24.

https://link.springer.com/content/pdf/10.1186/s40035-026-00557-1.pdf

Abstract

Background

The global rise in obesity prevalence poses a major health challenge due to its links to hypertension, stroke, type 2 diabetes, cardiovascular disease, depression, and cancer. Effective non-pharmacological strategies are essential to curb this epidemic. Insulin is a major regulator of body weight. It not only mediates glucose uptake but also inhibits hepatic glucose production, lipolysis, and enhances lipogenesis.

Main body

Type 1 diabetes provides insights on insulin’s role in weight regulation. Prior to diagnosis, insulin deficiency commonly produces unintentional weight loss, whereas initiation of exogenous insulin therapy typically restores body mass. Scientific research in non-diabetic populations, including Mendelian randomization studies, has identified elevated insulin secretion as a key contributor to weight gain. Conversely, reductions in insulin secretion have been shown to facilitate weight loss, even in the absence of caloric restriction. One strategy to keep circulating insulin concentrations low is the application of carbohydrate unit tables to estimate expected postprandial glucose excursions in insulin-deficient patients and anticipated insulin responses in non-diabetic individuals. This approach facilitates avoidance of foods that provoke large insulin responses. A complementary approach is postprandial self-monitoring of blood glucose (SMBG). In non-diabetic individuals, this allows for personalized assessment of glycemic and insulin responses to meals. The effectiveness of this approach in promoting weight reduction has been demonstrated across multiple studies. During fasting or adherence to low-carbohydrate diets, circulating insulin concentrations remain low, permitting unrestrained adipose tissue lipolysis and promoting fatty acid oxidation for energy production. Self-monitoring of breath acetone (SMBA) provides a simple, non-invasive biomarker of this metabolic state. Recent findings indicate that a single carbohydrate-rich meal during a ketogenic state suppresses fat mobilization for several days—a phenomenon suggestive of a “memory effect” of insulin on lipolysis inhibition. Although underlying mechanisms remain to be elucidated, awareness of this effect may improve dietary regimens.

Conclusions

Insights from type 1 diabetes offer advice for managing weight development by minimizing episodes of hyperinsulinemia. Effective non-pharmacological measures include the use of carbohydrate unit tables combined with SMBG for avoiding post-meal hyperglycemia and hyperinsulinemia. Additionally, SMBA provides a non-invasive marker of sustained fat mobilization and can help identify and prevent periods of insulin-induced fat accumulation.

Martin, Stephan, Kerstin Kempf, and Hubert Kolb. "Why hyperinsulinemia is detrimental to weight loss: insights from type 1 diabetes." BMC medicine (2026).

https://link.springer.com/content/pdf/10.1186/s12916-026-04849-1.pdf

Abstract

The role of dietary fat in human health remains debated, particularly in aging. The diet–heart hypothesis of the 1950s linked saturated fat to cardiovascular disease (CVD), shaping nutrition guidelines for decades. However, later trials yielded inconsistent results, and recent reviews have questioned the strength of this association. At the same time, studies of ketogenic and other high-fat diets suggest that, in specific metabolic contexts, higher fat intake may offer metabolic and vascular benefits. These findings highlight the need to move beyond simplified views of dietary fat by considering fat type, metabolic state, and eating patterns. Beyond cardiovascular outcomes, interest has grown in how diet influences brain aging and cerebrovascular health. Cerebrovascular dysfunction is central to vascular cognitive impairment and dementia (VCID), yet dietary effects on these mechanisms remain incompletely understood. This review examines evidence on how dietary fat composition and eating strategies affect endothelial function, cerebral blood flow, blood–brain barrier integrity, inflammation, and mitochondrial function within the aging neurovascular unit, identifying pathways that may support cerebrovascular resilience and cognitive health.

Negri, Sharon, Madison Milan, Rakesh Rudraboina, Eva Troyano-Rodriguez, Aleksandra Kosmider, Shantipriya Awasthi, Jennifer Ihuoma et al. "Rethinking dietary fat for the aging brain: the roles or ketosis and fat quality in cerebrovascular aging and VCID." Critical Reviews in Food Science and Nutrition (2026): 1-17.

https://www.tandfonline.com/doi/pdf/10.1080/10408398.2026.2672544?casa_token=BwItN0Mj91wAAAAA:swRuC4EfDFZR2qp1cN4oSaaqkzu7lifYSyrV1sry1OEO5xPxfAWeXo7_yOS-zK2SefqiC_5qUpQ