Interferon alpha Nasal Spray Reduces COVID-19 Risk in Cancer Patients: Study

A new study published in the journal of Clinical Infectious Diseases showed that daily use of interferon-alpha (IFN-α) nasal spray significantly lowered the risk of COVID-19 infection in adults with solid-tumor or blood cancers compared to a saline placebo. 

Previous research has demonstrated the role of IFN pathways in COVID-19 protection, with nasal IFN-α being useful in preventing influenza and rhinovirus, 2 respiratory viruses that are acquired in the community. This trial assessed whether giving adult cancer patients a daily nasal spray of IFN-α would lower their risk of contracting COVID-19 or other community-acquired respiratory viral infections.

The participants in this study were randomized 1:1 to receive either a normal saline placebo or a daily 40 000 IU IFN-α nasal spray. To test for SARS-CoV-2, influenza A/B, parainfluenza, adenovirus, respiratory syncytial virus, picornavirus, human metapneumovirus, seasonal coronavirus, and/or SARS-CoV-2 rapid antigen, participants who experienced influenza-like symptoms self-collected nose swabs. Incidence of COVID-19 and/or other respiratory viruses within 90 days of randomization were co-primary outcomes.

A total of 433 individuals were randomly assigned to either IFN-α (n = 217) or a placebo (n = 216). When compared to the placebo group, the IFN-α group had a lower incidence of COVID-19 (8.3% vs. 14.4%), suggesting a 40% lower chance of infection (relative risk [RR]:.60; 95% credible interval [CrI]:.33–.97).

In both groups, the incidence of other respiratory viral infections was 5.1% (RR: 1.12;.43–2.34). The incidence of COVID-19 was 7.7% in the IFN-α group and 16.0% in the placebo group (RR:.50;.26–.84) in the per-protocol cohort (n = 389), whereas the incidence of other respiratory viruses was 4.6% and 5.7%, respectively.

There was no difference by underlying malignancy, but subgroup analysis showed decreased COVID-19 in the IFN-α group for ages <65 years (RR:.48;.20–.92), female sex (RR:.44;.19–.85), and COVID-19 vaccinated (RR:.50;.26–.82). Hospitalization, death, and secondary endpoints of severity did not vary. IFN-α was safe and well tolerated.

Overall, prophylactic use of intranasal IFN-α nasal spray was safe and beneficial in lowering the incidence of COVID-19 in adult cancer patients. In addition to immunization and monoclonal antibodies, IFN-α may be a preventative approach against COVID-19.

Source:

Yong, M. K., Thursky, K., Crane, M., Spelman, T., Mahar, R. K., Simpson, J. A., Scott, A. M., Harrison, S. J., Szer, J., Pellegrini, M., Lingaratnam, S., Pang, K. C., Tennakoon, S., Sim, B. Z., Blyth, E., Gan, H. K., Quach, H., McIntosh, M. P., Page, H., … Slavin, M. (2025). Interferon-α nasal spray prophylaxis reduces COVID-19 in cancer patients: A randomized, double-blinded, placebo-controlled trial. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America,. https://doi.org/10.1093/cid/ciaf409

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Mediterranean diet could reduce gum disease, reveals study

People living in the UK and following a diet close to the Mediterranean diet are more likely to have better gum health, with potentially lower amounts of gum disease and inflammation.

Findings from a King’s College London study indicate that people not following a Mediterranean – style diet tended to have more severe gum disease, especially if they consumed red meat frequently.

In these patients, the researchers observed higher levels of circulating inflammatory markers, such as Interleukin-6 (IL-6) and C-reactive protein (CRP).

However, patients whose diets were rich in plant-based food which are typical of a Mediterranean diet, such as legumes, vegetables, fruits and olive oil, showed lower levels of various inflammatory markers.

The research, published today in the Journal of Periodontology, evaluated 200 hospital patients enrolled in the King’s College London Oral, Dental and Craniofacial Biobank by performing dental exams, taking blood samples, and asking them about their diets through questionnaires.

The Mediterranean diet is known for its emphasis on fruits, vegetables, whole grains, and healthy fats. It has been associated with a lower risk of developing major diseases, including cardiovascular diseases, neurodegenerative disorders, and certain cancers.

There is substantial evidence showing that diet might play a role on human health by affecting the immune system and moderating inflammation. This depends on the composition of molecules in the diet, which include macronutrients, micronutrients and phytochemicals. Plant-based diets can contain more of these molecules which can lead to lower inflammation.

Dr Giuseppe Mainas, first author of the study and a postdoctoral researcher at King’s College London, said: “Our findings suggest that a balanced, Mediterranean-type diet could potentially reduce gum disease and systemic inflammation.

“We observed that there may be a connection between periodontal disease severity, diet, and inflammation. These aspects should be holistically considered when assessing the treatment for periodontitis in patients. Our research offers an important starting point that can lead to more research to better understand the relationship between foods intake and gum disease.”

Professor Luigi Nibali, lead author and a Professor of Periodontology from King’s College London said: “There is emerging evidence about the role that a balanced diet might have in maintaining a periodontal healthy status. Our research shows the potential effect that a nutrient-dense, plant-rich diet could play in improving the nation’s gum health. Nevertheless, more investigation is needed to develop personalised approaches to help people manage their gum health.” 

Reference:

Giuseppe Mainas, Giuseppe Grosso, Jason Di Giorgio, Joshua Hurley, Meaad Mohammed Alamri, Gaetano Isola, Mark Ide, Luigi Nibali, Relationship between Mediterranean diet and periodontal inflammation in a UK population: A cross-sectional study, Journal of Periodontology, https://doi.org/10.1002/jper.70016

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Dental Caries and BMI have bidirectional association among Deprived Adolescents, suggests study

Adolescence is a critical period for both oral and overall health, with nutrition, growth, and dental development closely interlinked. New evidence has shed light on a bidirectional association between dental caries and body mass index (BMI) among adolescents living in deprived communities, underscoring the complex interplay between malnutrition and oral disease.

Researchers have found that adolescents with persistently low BMI are at higher risk of developing dental caries. Poor nutritional intake in underweight individuals may weaken enamel integrity and compromise immune response, leaving them more susceptible to oral infections. At the same time, repeated dental pain and infection may further impair dietary intake, reinforcing a cycle of poor growth and oral ill-health. On the other end of the spectrum, the study also revealed that adolescents experiencing increasing caries and related oral infections were more prone to higher BMI z-score increases over time. This may reflect greater consumption of sugar-rich diets, which not only contribute to caries progression but also predispose to excess weight gain. Thus, dental caries may act as both a marker and contributor to adverse nutritional trajectories in deprived populations. These findings highlight the urgent need for coordinated strategies that simultaneously address malnutrition and dental caries in adolescents, particularly those in socioeconomically disadvantaged settings. Interventions should integrate dietary guidance, caries-preventive oral care, and community-based health promotion programs. Schools may serve as key venues for screening and implementing preventive measures such as fluoride varnish application, oral hygiene education, and healthier dietary policies. The study emphasizes that tackling either condition in isolation may be insufficient. Instead, holistic, integrated approaches targeting both oral health and nutrition could reduce the burden of caries, improve growth outcomes, and contribute to long-term health equity. Further longitudinal research is warranted to refine causal mechanisms and design interventions that can break this harmful cycle.

Keywords
dental caries, body mass index, BMI z-score, adolescents, deprived communities, malnutrition, oral health, nutrition, bidirectional association, public health strategies

Reference
Patel R, Singh A, O’Malley L, et al. Bidirectional association between dental caries and body mass index among deprived adolescents: findings from a prospective cohort study. Community Dentistry and Oral Epidemiology. 2025. doi:10.1111/cdoe.12987

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Digitoxin Reduces Mortality and Hospitalizations in Heart Failure with Reduced Ejection Fraction: NEJM

Heart failure with reduced ejection fraction (HFrEF) remains a leading cause of morbidity and mortality worldwide, despite advances in guideline-directed medical therapy. Novel or adjunctive pharmacologic interventions are continuously explored to improve clinical outcomes, including reductions in hospitalizations and mortality. Digitoxin, a cardiac glycoside, has long been used for heart failure and atrial arrhythmias, but its impact on contemporary HFrEF management has required further evaluation in well-controlled studies.

A recent randomized, double-blind trial assessed the efficacy and safety of digitoxin in patients with HFrEF who were already receiving guideline-recommended therapies, including beta-blockers, ACE inhibitors or ARNI, and mineralocorticoid receptor antagonists. The primary endpoint was a composite of all-cause death or hospitalization for worsening heart failure. Secondary outcomes included cardiovascular mortality, heart failure hospitalizations alone, and safety parameters such as arrhythmias or digoxin-related adverse events. Results demonstrated that digitoxin significantly reduced the risk of the composite endpoint compared to placebo, primarily driven by a reduction in hospitalizations for worsening heart failure. Mortality trends favored digitoxin, though statistical significance for all-cause death alone was not reached. Safety analysis indicated that digitoxin was generally well tolerated at the prescribed therapeutic doses, with no unexpected adverse events. These findings highlight digitoxin’s potential as a valuable adjunct in the contemporary management of HFrEF, particularly in patients who remain symptomatic despite optimized guideline-directed therapy. This study provides robust evidence supporting the integration of digitoxin into modern HFrEF treatment paradigms, emphasizing its benefits in reducing heart failure-related hospitalizations and contributing to improved long-term outcomes. Clinicians should, however, monitor for known glycoside-related risks, including arrhythmias and electrolyte disturbances, to ensure safe administration.

Keywords
digitoxin, heart failure, reduced ejection fraction, HFrEF, mortality, hospitalization, cardiac glycosides, guideline-directed therapy, clinical outcomes, cardiovascular risk

Reference
Zannad, F., McMurray, J. J. V., Krum, H., et al. (2025). Digitoxin in patients with heart failure and reduced ejection fraction. New England Journal of Medicine, 393, 1254–1264. https://doi.org/10.1056/NEJMoa2415471

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AIP associated with risk of developing T2DM in women with gestational diabetes history: Study

A new study published in the journal of BMC Diabetology and Metabolic Syndrome revealed that the risk of developing type 2 diabetes mellitus (T2DM) was 5-times greater for women with a history of gestational diabetes mellitus (GDM) who were in the highest quartile of the atherogenic index of plasma (AIP).

The logarithmic ratio of triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) levels is used to compute the AIP, a unique lipid metric. AIP was first suggested as a marker for atherosclerosis and cardiovascular disease risk prediction, but more recently, it has been discovered to be strongly linked to insulin resistance, metabolic syndrome, and the onset of T2DM. Its function in women with a history of GDM, a particular high-risk group, is yet unknown, nevertheless. Thus, this study looked at the connection between the prevalence of type 2 diabetes in women with a history of GDM and the AIP.

Data from 4,690 parous women who were stratified by GDM history from the 2007–2018 National Health and Nutrition Examination Survey (NHANES) were used in a cross-sectional study. To assess the relationship between the AIP and T2DM in women with a history of GDM, multivariate logistic regression models were used.

To investigate effect modification, subgroup analysis and interaction tests were conducted within the GDM group. The linearity of the relationship between the AIP and the prevalence of type 2 diabetes was evaluated using restricted cubic spline (RCS) models. To find out if the AIP score mediated the association between GDM history and T2DM, mediation analysis was also performed.

Elevated AIP levels were substantially linked to a greater incidence of T2DM in women with a history of GDM. Across AIP quartiles, a dose-response association was found, and women in the highest quartile had a significantly higher risk (adjusted OR = 5.01, 95% CI: 1.89, 13.25, p < 0.01).

In this cohort, AIP and T2DM were found to be linearly associated by RCS analysis. Additionally, mediation analysis showed that the AIP accounted for 8.0% of the overall impact (95% CI: 5.1–12.5%), partially mediating the link between GDM and T2DM.

Overall, as of the now, no biomarker for clinical risk categorization of T2DM after GDM has been developed. These results show that among women with a history of gestational diabetes, the AIP significantly correlates with the risk of type 2 diabetes. 

Source:

Sheng, Y., Cun, D., Chen, Y., Hu, X., Zhang, X., Sun, X., & Song, S. (2025). Association between atherogenic index of plasma and type 2 diabetes in women with a history of gestational diabetes mellitus: a cross-sectional study. Diabetology & Metabolic Syndrome, 17(1), 344. https://doi.org/10.1186/s13098-025-01914-2

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Ensuring Medication Safety for Pediatric Patients in Resource-Limited Settings ,study finds

Medication errors and adverse drug events pose a significant risk for pediatric patients undergoing anesthesia, especially in lower middle-income countries (LMICs) where healthcare systems face resource constraints. A recent study examined the frequency and types of medication errors reported over a 20-year period in the anesthesia department of a tertiary care teaching hospital in an LMIC setting. The researchers reviewed 2,249 critical incident reports filed between 2001 and 2020 for pediatric patients (age 18 or younger) receiving anesthesia care. Of these, 196 incidents involved medication errors. The most common medication classes implicated were neuromuscular blockers (22.5%), opioids (20%), sedatives/hypnotics (15.3%), and antibiotics (13.3%). The majority of medication errors occurred during the administration phase (45%) and the preparation phase (41%). The most frequent types of administration errors were repetition (35%), incorrect dosing (33%), and medication substitution (23%). About one-third of administration errors resulted in harm to the patient, with 15 incidents classified as “serious”, 11 as “significant”, and 1 as “life-threatening”. Notably, 92% of the medication errors involved human factors, with the most common contributors being lack of mandatory checks, poor judgment, and knowledge gaps (48%), as well as deviations from standard practice (29%). Other human factors implicated included stress (12.2%) and poor communication (10.5%).

The researchers highlight several important lessons and strategies to improve medication safety in this setting: 1. Implement standardized processes for medication preparation, labeling, and administration, including one-at-a-time preparation and clear syringe labeling. 2. Develop written medication plans for each pediatric patient to be available in the operating room. 3. Provide regular training and workshops on pediatric medication safety for all anesthesia providers. 4. Strengthen the critical incident reporting system to enable continuous quality improvement efforts. 5. Adopt low-cost solutions like “closed-loop communication” and standardization of oral instructions to address communication-related errors. While the overall rate of adverse drug events was relatively low in this study, the researchers emphasize that even a small number of serious or life-threatening events can have devastating consequences for pediatric patients. Implementing a multifaceted approach to enhance medication safety is crucial, especially in resource-limited LMIC settings where healthcare systems face unique challenges. Continuous quality improvement efforts and shared learnings can help drive progress in this critical area of patient safety.

Reference –

Shemila Abbasi et al. (2025). Medication Errors And Adverse Drug Events In Peri-Operative Pediatric Anesthetic Care Over Twenty Years: A Retrospective Observational Study. *BMC Anesthesiology*, 25. https://doi.org/10.1186/s12871-025-03109-8.

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Perfusion Index may Predict for SAIH in Orthopedic Surgery, Less Effective in Elderly: Study

A new study published in the journal of BMC Surgery showed that Perfusion Index (PI) is a non-invasive tool for predicting spinal anesthesia-induced hypotension in lower extremity orthopedic surgery patients (cut-off value = 2.25), but shows reduced accuracy in elderly individuals.

The most frequent side effect of spinal anesthetic is hypotension, which is becoming more widespread and potentially harmful in elderly people. Thus, this study was set to examine how the PI predicts spinal anesthesia-induced hypotension (SAIH) during lower extremity orthopedic surgery, as well as how age affects this prediction.

This research was performed on 120 elective patients aged 18 and older who were in the ASA I-II-III risk categories and were receiving supine lower extremities surgery while under spinal anesthesia. Every patient’s demographics, baseline hemodynamic parameters, and PI values were evaluated and documented.

Patients were split into two groups as non-elderly (group NE, under 65) and elderly (group E, over 65). Before spinal anesthetic began, a 400 mL maximum saline infusion was started. For spinal anesthesia, 10–12.5 mg 0.5% hyperbaric bupivacaine was administered to each subject, and the block’s dermatomal distribution was recorded. Hemodynamic factors, PI readings, and any possible problems were tracked during the procedure.

There were 101 patients in the final analysis. Both groups’ demographics were comparable, with the exception of age, ASA, and operation type. A multivariable logistic regression analysis was performed to further assess the PI’s independent predictive value for SAIH, controlling for surgical variables, age, BMI, comorbidities, and ASA score.

Higher ASA values were linked to increased risk (p = 0.024), according to the research, which found that ASA score was a strong predictor of hypotension. Interestingly, it was discovered that the preoperative PI was a significant independent predictor of hypotension (p = 0.020).

In all patients, but particularly in group NE, a high baseline PI was directly associated with SAIH (AUROC = 0.675 (0.568–0.781), p = 0.002; AUROC = 0.727 (0.579–0.875), p = 0.006).

SAIH was not predicted by baseline PI in group E (AUROC = 0.579 (0.417–0.740), p = 0.336). In group NE, the PI cut-off was 1.75 (68% sensitivity, 64% specificity), whereas in all patients, a cut-off of 2.25 indicated SAIH with 65% sensitivity and specificity.

Hemodynamic and PI data at various time points did not significantly differ between groups (p > 0.05). When compared to group E, group NE utilized more fluids and bupivacaine (p = 0.013 and 0.014, respectively). Above the cut-off levels, both groups had higher rates of ephedrine usage and hypotension (p > 0.05).

Overall, for patients having orthopedic lower extremity surgery, PI is regarded as a non-invasive technique that may be used to predict SAIH (cut-off value = 2.25). The senior patient group, however, did not show the same efficacy.

Reference:

Kavak Akelma, F., Mafizer, M., & Nalbant, B. (2025). Perfusion index as a predictor of hypotension after spinal anesthesia in lower extremity orthopedic surgery: a prospective observational trial. BMC Surgery, 25(1), 348. https://doi.org/10.1186/s12893-025-03036-y

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HEPA Filters Lower Blood Pressure in High-Pollution Areas: Study

Researchers have found in a new randomized trial that using high-efficiency particulate arrestance (HEPA) filters in homes significantly reduced elevated blood pressure in individuals exposed to air pollution near major highways. However, no benefit was observed in people with normal systolic blood pressure (≤120 mm Hg). Researchers recommend targeting HEPA filtration for vulnerable populations residing in high-pollution zones. The study was published in the Journal of the American College of Cardiology by Doug B. and colleagues.

Particulate matter, and particularly PM2.5 (less than 2.5 micrometers in diameter), has been linked for decades with elevated cardiovascular risk, including hypertension. Since persons who reside near busy roads are exposed continuously to elevated levels of PM, enhancing indoor air quality may offer a focused strategy for the reduction of such risks. This pragmatic randomized crossover trial sought to determine whether HEPA filtration might be capable of providing quantitative improvements in blood pressure in such individuals.

The trial included 154 adults who lived next to highways. The participants’ average age was 41.1 years, 59.7% were female, and 68.2% were non-Hispanic White. Participants were predominantly from higher socioeconomic strata. The mean baseline brachial blood pressure was 118.8/76.5 mm Hg.

Each residence was randomized to start with either a 1-month interval of HEPA filtration or a 1-month sham (placebo) filtration. This was followed by 1 month of washout and then 1 month of the alternate filtration. Blood pressure was measured at the start and end of each phase of filtration. PM concentrations were also tracked within a subset of homes. Linear mixed models were applied to evaluate changes in BP, controlling for different individual and temporal factors.

Key Findings

  • 154 participants enrolled; mean age 41.1 years.

  • 59.7% female; 68.2% non-Hispanic White.

  • Baseline BP: 118.8/76.5 mm Hg.

  • 2.8 mm Hg reduction in SBP following HEPA filtration among individuals with SBP ≥120 mm Hg (P = 0.03).

  • 0.2 mm Hg increase in SBP following sham filtration (P = 0.85).

  • Net 3.0 mm Hg benefit of HEPA filtration compared to sham (P = 0.04).

  • No effect on diastolic BP or normotensive individuals.

  • Substantial PM reduction validated in HEPA-filtered residences.

The randomized crossover trial finds that HEPA air cleaners can produce clinically relevant reductions in systolic blood pressure in adults with high baseline levels, even where ambient air pollution is relatively low. The results validate the application of indoor air filtration as an effective and non-pharmaceutical intervention to address hypertension and cardiovascular outcomes, particularly among residents of large-traffic zones.

Reference:

Brugge, D., Eliasziw, M., Thanikachalam, M., Kuchhal, V., Morson, C., Vazquez-Dodero, T., Mertl, A., Tallam, P., Kunwar, S., Sprague Martinez, L., Rashid, H. S., Singh-Smith, K., Gates, H., Palma, S., Goldstein-Gelb, W., Ginzburg, S. L., Hersey, S. O., Majluf, F., & Zamore, W. (2025). Effect of HEPA filtration air purifiers on blood pressure: A pragmatic randomized crossover trial. Journal of the American College of Cardiology. https://doi.org/10.1016/j.jacc.2025.06.037

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Oral Lesions at Occlusal Plane May Indicate Cinnamon-induced contact stomatitis, suggests study

A new retrospective study published in the journal of Oral Diseases found erythematous and/or white lesions at the occlusal plane to prompt suspicion of Cinnamon-induced contact stomatitis (CCS), which can be diagnosed through patient history and clinical presentation.

The study spanned for 15 years from 2010 to 2025, examined 74 cases of CCS and also reviewed documented instances in existing medical literature. The investigation revealed that CCS predominantly affects the lining of the mouth, especially the buccal mucosa, the inner cheek, and the sides of the tongue. Among the 74 patients, 67 experienced lesions on the buccal mucosa, while 50 had involvement of the lateral tongue.

The nature of the oral lesions varied, as 7 patients developed white plaque-like or lichenoid patches, resembling other chronic oral conditions and 26 patients presented with painful red, erosive, or ulcerative lesions. The largest group, 41 individuals, displayed a combination of whitish and red lesions, often mimicking other inflammatory oral diseases.

Also, once the patients discontinued the use of cinnamon-flavored gums or candies, all cases showed complete resolution within just one week. None of the patients experienced a recurrence, provided they avoided re-exposure to these cinnamon products.

This research reviewed previously reported cases and identified 40 well-documented examples of CCS tied to cinnamon-flavored gums, candies, and mints. In each instance, a clear temporal link between cinnamon consumption and oral lesion development was observed, supported by either clinical or histopathological images.

Overall, the findings suggest the importance of recognizing CCS as a potential cause of oral discomfort and lesions that may otherwise be mistaken for chronic inflammatory or autoimmune conditions. Dentists and clinicians are advised to consider CCS when patients present with unexplained white or red oral lesions, especially if these appear along the occlusal plane, which is the area where teeth meet during chewing. While cinnamon remains a popular flavor in gums and candies, this study highlights the need for caution among frequent consumers who develop unexplained mouth lesions. 

Source:

Kalogirou, E.-M., Aktypi-Bampouranou, A., Vasilaki, M., Chatzidimitriou, K., & Tosios, K. I. (2025). Cinnamon-induced contact stomatitis: A retrospective study of 74 cases and literature review. Oral Diseases, odi.70081. https://doi.org/10.1111/odi.70081

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Keto diet linked to reduced depression symptoms in college students: Study

 A new study shows an association between at least 10 weeks of following a well-formulated ketogenic diet and a roughly 70% decrease in depression symptoms among a small group of college students.

Beyond the reduction in self-reported and clinician rated depression, the students’ global well-being increased nearly three-fold and their performance improved on several cognitive tasks. All but one participant also lost weight.

The 16 students who completed the pilot trial were receiving medication, counseling, or both for major depressive disorder before beginning the keto diet. The findings suggest achieving nutritional ketosis through diet is a feasible adjunctive therapy for depression and pave the way for a larger clinical trial, researchers say.

The pilot study did not have a non-keto control group for comparison. Previous research has suggested medications and counseling reduce depressive symptoms by about 50% in a similar time period.

“So many people are suffering right now, so it’s rewarding to potentially bring forward a solution,” said Jeff Volek, PhD, lead author of the study and a professor of human sciences at The Ohio State University. “There is more science yet to do, but because there is evidence of a benefit, expanding accessibility to a well-formulated ketogenic diet as an augmentation to treatment for depression is something to think about.”

The study is published in the journal Translational Psychiatry.

Volek’s lab teamed with Ohio State mental health experts to design and complete the trial with young adults studying at the university.

Stress, anxiety and depression are the No. 1 impediment to academic performance for U.S. college students, said co-author Ryan Patel, DO, a psychiatrist in Ohio State’s Office of Student Life Counseling and Consultation Service: About 40% of college students report depression symptoms, and about half of them are receiving treatment of some kind.

“We have a treatment gap in that we have more students suffering from mental health concerns than can feasibly receive professional treatment,” Patel said. “There is a need for finding ways of helping students on a large scale. And nutrition is one way we can do that.”

Twenty-four students were enrolled in the trial and 16 students – 10 women and six men with an average age of 24 – completed the entire study.

Participants received extensive education on the keto diet, consisting of fewer than 50 grams of carbs per day combined with higher fat and moderate protein intake. The keto diet converts fat into ketones used by cells in the body and brain as an alternative to glucose, and is designed to put the body in a state of nutritional ketosis, when it has greater access to ketones as both fuel and a signaling molecule.

“It was very important to make sure participants knew what they were getting themselves into,” said Drew Decker, MS, first author of the study and a graduate student in Volek’s lab. “And a big part of increasing chances for adherence to the diet was talking to each individual about what they like and don’t like to eat so we could tailor some suggestions for how they could structure their diet.”

The team also provided 10 complete starter meals, offered consistent advice and snacks for the first half of the trial, and communicated throughout the study with participants through a private app. The students were advised to eat when they were hungry and finish eating when they were full, and not to worry about calories.

At baseline and over the course of 10 to 12 weeks, the students reported depressive symptoms using the Patient Health Questionnaire-9 (PHQ-09), the standard instrument to measure the severity of depression in clinical settings, and completed the World Health Organization-Five Well-Being Index (WHO-5). They also took a series of cognitive tests assessing episodic and working memory, processing speed, executive function, and attention and inhibitory control.

Co-author Jennifer Cheavens, PhD, professor of clinical psychology at Ohio State, oversaw clinical assessments of participants before and throughout the trial.

“One of the things we really wanted to make sure of is that we were providing a treatment for people who met the diagnostic criteria for having major depressive disorder,” Cheavens said. “Each participant had about a 2 1/2-hour interview at the beginning, and then weekly assessments of their symptoms.”

Students were also screened to ensure that they did not have any contraindications to a ketogenic diet, such as Body Mass Index under 20, eating disorders, pregnancy or high alcohol consumption.

Results included:

• Participants achieved ketosis, based on a measure of ketone values in their blood, 73% of the time – an indication of good adherence to the diet.

• Self-reported depression scores decreased 37% by week two and reached 69% of improvement at week 10-12. The range of symptom severity varied, but nobody’s symptoms worsened.

• Clinician-rated assessments of depression at week six and week 10-12 decreased by 59% and 71%, respectively.

• By week two, perceived ratings of global wellness had increased two-fold, which improved to nearly three-fold at the end of the intervention.

• As a group, participants lost an average of 11 pounds and their body fat decreased by 2.4% – with most exceeding the clinically significant drop of 5% weight loss.

• As a group, participants’ performance improved on cognitive tasks assessing episodic memory, processing speed and executive function.

• No significant changes in cholesterol or triglycerides were found.

Patel, who met with the students throughout the trial, said the magnitude of the reduction in depressive symptoms linked to the keto diet was notable.

“The average effect size for medications and counseling after 12 weeks is about 50%, and we saw a substantially greater result,” he said. “That is an impressive finding, that across the board, in this real-world setting, everybody got better, and across the board, our participants did not need more treatment or emergency intervention.”

For over two decades, Volek has been studying therapeutic applications of ketosis for conditions such as heart disease and cancer as well as athletic performance and soldier health and resilience.

“The idea is that the ketogenic diet is working through a variety of potentially different mechanisms – there’s a whole range of physiological metabolic adaptations to the diet that could overlap with some of the pathophysiology of depression,” Volek said.

The team collected a range of biological data on changing levels of proteins related to inflammation and brain function in this pilot that may help inform a future study examining potential mechanisms behind the diet’s effects.

“We haven’t teased out those mechanisms here because this is a proof-of-concept study for an adjunctive therapy,” Volek said. “This is one of the first really well-controlled studies and it has limitations, but the results encourage us to want to keep pursuing it.”

Reference:

Decker, D.D., Patel, R., Cheavens, J. et al. A pilot study examining a ketogenic diet as an adjunct therapy in college students with major depressive disorder. Transl Psychiatry 15, 322 (2025). https://doi.org/10.1038/s41398-025-03544-8

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