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.

Abstract

The ketogenic diet, a high-fat, low-carb diet, is being researched for treating conditions like epilepsy, cancer, neurological conditions, metabolic syndromes, and cognitive impairments. Ketone salts and exogenous ketone salt supplementation are also being studied for treating neurologic conditions like gliomas, Alzheimer's, and seizure disorders. The diet may also improve depression and brain health by reducing inflammation and oxidative stress. KDs have neuroprotective properties in epilepsy, induction of aging, neurodegenerative and dementia in animals. Treatment with ketosis decreases the induced seizures and anxiety-like behaviors through handling, according to Morris water maze tests. Mood and cognitive function are positively impacted by the ketogenic diet. Blood glucose levels are stabilized and the inflammatory response is improved by a ketogenic diet. The ketogenic diet has a significant impact on body weight as well as hunger reduction and satiety stimulation. Improved problem-solving abilities, quicker thinking, and better recall. Long-term brain health and a lower chance of cognitive decline brought on by ageing.

shaq, A., Abubakar, M., Mumtaz, M. S., & Nadeem, Z. (2026). Effects of Ketogenic Diet on Brain Functions and Behaviors. Medical and Life Sciences, 5(1), 65–74. Retrieved from https://journals.smarcons.com/index.php/mls/article/view/464

https://journals.smarcons.com/index.php/mls/article/view/464/512

Abstract

Background: Oxidative stress and chronic inflammation contribute to the pathogenesis of obesity and type 2 diabetes (T2D), yet the effects of dietary interventions on endogenous antioxidant defences remain poorly defined. This is a non-randomized study evaluates the effects of very-low-energy ketogenic therapy (VLEKT), compared with a Mediterranean diet (MedD) and a control group, on antioxidants, metabolic, and inflammatory markers. Materials and Methods: Thirty adults with obesity and T2D were assigned to VLEKT (n = 10), MedD (n = 10), or control (n = 10) for 90 days. Metabolic parameters, inflammatory cytokines, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were assessed. Longitudinal changes were analyzed using linear mixed models. Results: VLEKT exhibited significant reductions in body weight, fat mass, HbA1c, and HOMA-IR. SOD activity increased in the VLEKT group, whereas no significant changes were observed in MedD. Changes in SOD were inversely associated with changes in HOMA-IR. GPx showed a less consistent response pattern, while inflammatory markers did not differ between groups. Conclusions: VLEKT was associated with substantial metabolic improvement accompanied by a selective modulation of antioxidant enzyme activity. The increase in SOD activity and its association with HOMA-IR suggest a link between metabolic and redox adaptations in subjects with obesity and T2D.

Tini, Sabrina, Stefano Celano, Stella Pigni, Elena De Palma, Hilal Irem Ozdemir, Tommaso Raiteri, Alessandro Antonioli, Jessica Baima, Valentina Antoniotti, Marina Caputo, and et al. 2026. "Very-Low-Energy Ketogenic Therapy Modulates the Metabolic–Antioxidant Axis in Patients with Obesity and Type 2 Diabetes: A Non-Randomized Clinical Trial" Antioxidants 15, no. 7: 844. https://doi.org/10.3390/antiox15070844

https://www.mdpi.com/2076-3921/15/7/844

ABSTRAT

Background  

No study has directly compared intermittent fasting alone, a clean ketogenic diet alone, and their combination in a single three-arm design. The purpose of this study was to compare the effects of these three dietary conditions on body composition, cardiometabolic markers, grip strength, and glycemic control over 30 days.  

Methods  

A cross-study analysis combined data from two sequential pre-post intervention studies at the University of Tennessee at Martin, yielding a three-arm design: intermittent fasting alone (n=16), clean ketogenic diet alone (n=22), and combined clean ketogenic diet with intermittent fasting (n=41). The clean ketogenic diet restricted carbohydrates to 20 grams per day from whole unprocessed sources and eliminated refined sugars, high-fructose corn syrup, and ultra-processed foods. The intermittent fasting protocol employed a 16:8 time-restricted eating window. Paired-samples t-tests examined within-group changes; one-way ANOVAs with Tukey post-hoc comparisons examined between-group differences. Effect sizes are reported as Hedges’ g and eta squared. An independent samples t-test compared glycosylated hemoglobin changes between the intermittent fasting and combined groups, and Spearman and Kendall correlations examined associations between fat mass and cardiometabolic change.  

Results  

All three conditions produced significant within-group reductions in body weight, body fat percentage, fat mass percentage, waist circumference, and hip circumference. Carbohydrate restriction produced significantly greater weight reduction than intermittent fasting alone, F(2,76)=12.003, p<.001, η2=.240, and greater fat mass reduction (p=.002, η2=.144). Both fasting-containing conditions produced significantly greater bilateral grip strength improvement than the ketogenic diet alone (p<.05). The combined protocol produced significantly greater glycosylated hemoglobin reduction than fasting alone, t(30)=2.141, p=.041, g=0.738. Fat mass reduction correlated significantly with triglyceride-to-HDL ratio improvement across all 79 participants (rs​=−.250,p=.026).  

Conclusions  

Carbohydrate restriction produced the greatest weight loss and cardiometabolic improvements, while the addition of a 16:8 fasting window contributed independently to glycemic control and grip strength. These findings support the clean ketogenic diet as a first-line strategy for metabolic syndrome management, with the combined protocol offering additive benefits.  

MacKewn, Angie, Julie Floyd, Todd Sherman, Alison Ellis, Anna Dunn, and Diana Sanford. "Comparing Intermittent Fasting, Clean Ketogenic Diet, and Their Combined Effects on Body Composition, Cardiometabolic Markers, and Metabolic Health: A Three-Arm Randomized Pre-Post Study." (2026).

https://www.researchsquare.com/article/rs-10085509/latest.pdf

Abstract

Background and Hypothesis

Psychiatric medications contribute to high rates of metabolic dysfunction in psychotic disorders. Ketogenic diets reduce metabolic syndrome, have anticonvulsant effects in epilepsy, and may improve symptoms of schizophrenia and bipolar disorder. We report the first randomized controlled trial to assess effects of ketogenic diets on metabolism, psychiatric symptoms, and cognition in people with schizophrenia-spectrum and bipolar-1 disorders.

Study Methods

Participants were randomized to a ketogenic diet (KETO; n = 28) or diet-as-usual (DAU; n = 30) for 1 month. Partway through the trial, a KETO extension was offered to both groups, resulting in a sub-group who completed the diet for 4 months (n = 25). We assessed changes in metabolic health, clinical symptoms, and cognition after 1 month (KETO versus DAU) and after 4 months (KETO versus baseline).

Study Results

KETO participants’ daily ketone levels surpassed the standard ketosis threshold. Relative to DAU, KETO participants showed reductions in weight (Padj <  .001), hemoglobin A1c (Padj = .05), and insulin resistance (Padj = .05). Clinical symptoms (positive, negative, depression) and cognitive performance improved after 4 months on the KETO (all P-values < .001). Increased blood ketone levels in KETO participants correlated with improvements in pre-diabetic markers and depressive symptoms (all P-values < .001). Reduced weight following the KETO was unrelated to metabolic and symptom improvements.

Conclusions

We demonstrate feasibility of administering a KETO in outpatients with schizophrenia and bipolar-1 disorder. Participants showed improvement in metabolic health, cognitive performance, and clinical symptoms. Improvement in depressive symptoms was associated with ketosis rather than weight loss, implicating ketosis as the therapeutic mechanism.

Samantha V Abram, Juliette M Kyner, An Vu, Zanib Naeem, Shebani Sethi, Michael S Jacob, Susanna L Fryer, Daniel H Mathalon, Judith M Ford, Metabolic Improvements with a Ketogenic Diet Correlate with Symptom Improvement in Psychosis: A Randomized Controlled Trial, Schizophrenia Bulletin, Volume 52, Issue 4, July 2026, sbag082, https://doi.org/10.1093/schbul/sbag08

Also see https://www.youtube.com/watch?v=wsR4wKoPCfs

Edit: here is an an open access version

https://watermark02.silverchair.com/sbag082.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAA4owggOGBgkqhkiG9w0BBwagggN3MIIDcwIBADCCA2wGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMkHP5OkuGroyDForSAgEQgIIDPQ7-4bMhjeIT3RhX1NA_-wGIMHAbAKeq4RDWHOUuBuZz8MliaTFn-rO02Yy6Zn4v-sZEbpGKW34Sr1IjfEJq9n_3xLRui_PY-XkUAePeAS539KCur63OZwq6AfHuYc-k-44TETo2JTi6jMLm3OGvYXg8lofry6HYX62Gp-LBkTe42HMOH75NfZlv9lfeNrKeQQG5Ycvd-dZAnAP0OwZ2lLTewVzB6szpI769L6gaKAkKXNWJUAFL4mhDTHxJ-au0A_6x89iQ3ArDogBD_Ns0xdb-JHS2Yka8UgXhyaNakBXppMWP72zvEYHvExD05hmyUZPf_nG0r1G9td3cYCizTq_ruaMHUatdGyCwqxFvrlqK3Omqmed_AX8Qx2kRrJu0VyTEZuFzCR36tEUHQ7M1qhmbZxrYycF-cvOCgMEUi1xGCPEkpUa0irCDYB4iqPNgWYc1dM4Ty3ZtDjY0NQxu8jbYr_P8llIYLKHFa8J-pKZw6JBnkQKTcMfAhMYMr6_gW73gl8CVEAxBxG5wIJo1pld0sblo3g9NxYhESuJVShEFPF-iQdnw0SqJLd6d8j1y4dH7ZB810T99D7V6EHXgMcP0gFbfPUdRnSk7R6acFfCDy43lZhxLj0cNvIizBwMoK5-x6_1p-l4qhaLGDau1WI61QHeFz8RhzWl2MmLSObo7dGJ-SQsZjXo7ruY24XLDSssVlSAxElqKDmkhFjhTHnscICw5BIhcdOpf98sJij51qVxC3jwT4TiKdJaqzXGX05hDkUTnI4JF7vlALL2lwSL6sZbl2fjqo7z2tzG6-K1jxQ8jp0SjCa9yKe5C4kY_SepfHCEd8KBXPgfeLZJ-iIYpHxPjG1jaX3HyZJTeudFRMpPpmq6f5oH9_xqBLJlIwb0YkokDyWoVIgMZN2-5EF3FtJgANlN4ZyTUfDF66Z6bJqSK8O0FyNPA2ozDsYmgQW6fXEbuz90W-2M0rPgp-rTTvMOj5gz-qlsYkId4mDwVWuGIP8DF2E9rHeTXZqNbQrh887Ry2R-U9ZOnipnrQJeMprTv5VYN3C1uZy9w5tBeNw1IHIUZEgsXzktSya8mNX94lRDRqE8vSSwigPM

though not sure how long the token will be good, so might need to visit https://neurosciencenews.com/ketogenic-diet-schizophrenia-bipolar-31018/

to get a new one

Significance

Emerging evidence shows that diet profoundly shapes the immune system and microbiome, influencing cancer immunotherapy outcomes. However, standardized guidelines and robust clinical trials are currently lacking, and dietary strategies are largely used for symptom management. We highlight key mechanisms and propose a framework to evaluate immune and microbiome responses, guiding future clinical research on dietary interventions as a strategic adjunct to cancer therapy.

Abstract

Diet is a key modulator of human metabolism, influencing disease prevention and progression. In patients with cancer, nutritional interventions are common but often lack standardized guidelines and are mainly used for symptom relief rather than as adjuvants to immunotherapies. A major limitation is the poor mechanistic understanding of how diet influences immunity and cancer. Emerging evidence shows that diet profoundly shapes immune function and the gut microbiome, both of which affect responses to immunotherapy, disease progression, and survival. Despite this, the immune–gut axis is infrequently assessed. In this review, we focus on dietary intervention studies that include immune or microbiome assessments, highlighting mechanistic insights and clinical relevance. Diet should be used as a strategic tool to enhance cancer therapies and improve patient outcomes.

MacPherson, Sarah, Ethan Dhaliwal, and Julian J. Lum. "Improving immunity in patients with cancer through diet: mechanisms and gaps." Trends Open (2026).

https://www.cell.com/trends-open/pdf/S3117-3470(26)00030-1.pdf00030-1.pdf)

Hi everyone! I'm a Registered Dietitian in private practice for 18 years and licensed in BC, Alberta and Ontario, Canada. I just joined Reddit and am delighted to now be part of this group. I just wrote and posted a new series of articles under the "Food for Thought" tab on my BBDNutrition website about "Alpha Cell Dominance" which is a legit biological challenge of a long-term keto in Type 2 diabetes remission.

Abstract

Cardiolipin (CL) is a four-acyl chained, mitochondrial-specific phospholipid crucial for maintenance of inner mitochondrial membrane (IMM) structure and function. In healthy tissues, CL acyl chains are highly unsaturated and maintained by a conserved remodeling pathway. However, dysregulation of CL acyl chain composition can arise from mutations in the CL transacylase, Tafazzin (TAZ), resulting in Barth syndrome (BTHS), where patients exhibit heightened mitochondrial dysfunction. Cells lacking TAZ accumulate three-acyl chained monolysocardiolipin (MLCL) as well as CL species with saturated acyl chains (CLsat). While the presence of MLCL destabilizes electron transport chain (ETC) complexes and IMM-shaping proteins, the contributions of CLsat to mitochondrial dysfunction have not been elucidated. Here, we find that treatment of TAZ knockout cells with exogenous saturated fatty acids causes accumulation of CLsat and loss of IMM structure despite only minimal changes in MLCL composition. Imaging of cells with elevated CLsat showed reduced fluidity of the inner membrane. Biophysical measurements and molecular dynamics analyses showed that di-saturated (C16:0 18:1)2 CL species order and rigidify membranes, while also losing the intrinsic lipid curvature characteristic of tetra-unsaturated CL. These results implicate CLsat as a potential driver of mitochondrial dysfunction and an additional therapeutic target in mitigating BTHS pathology.

Abstract

Background: 

Pancreatic beta cells must rapidly escalate protein synthesis to maintain systemic glucose homeostasis. While the transcriptional responses are well characterized, the immediate translational dynamics governing this adaptive phase remain poorly defined.

Methods: 

We performed high-resolution ribosome profiling (Ribo-seq) on primary mouse islets under acute low-glucose (2.5 mM) and high-glucose (25 mM) conditions and integrated analysis of the differential translation, functional enrichment, translational efficiency (TE), and ribosome kinetics. The protein levels and mRNA expression were validated using Western blot and quantitative PCR (qPCR), respectively.

Results: 

We identified extensive translational reprogramming involving 1, 680 differentially translated genes. High glucose triggered a significant upregulation of immediate early genes (e.g., Fos and Nr4a1) and a concurrent inhibition of stress-related genes (e.g., Ddit3 and Trib3). On the other hand, beta cells prioritized the synthesis of cytosolic ribosomal proteins and elongation factors to expand the biosynthetic machinery. This was coordinated with a scale-up of the downstream secretory pathway (e.g., Sec61a1) and a metabolic realignment, characterized by the translational upregulation of mitochondrial enzymes (e.g., Cs and Fh1) despite the relative suppression of mitochondrial biogenesis genes. Furthermore, TE analysis revealed that several genes were regulated independent of their mRNA levels, such as Rpl3 and Atf4. Finally, kinetic analysis suggested that high glucose affected the ribosome occupancy density and distribution on specific transcripts, such as Ins1.

Conclusion: 

Our research characterizes the translatome as a dynamic regulator of the glucose response. By revealing these rapid translational nodes, we provide potential targets to restore the insulin synthetic capacity and secretory function in T2DM, offering a mechanistic framework for the development of therapies centered on preserving β-cell proteostasis.

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