Dietary supplements for Parkinson's disease: State of the science.

BackgroundReductions in skeletal muscle mass and increased adiposity are key elements in the aging process and in the pathophysiology of several chronic diseases. Systemic low grade inflammation associated with obesity has been shown to accelerate the age-related decline in skeletal muscle. The aim of this investigation was to determine the effects of 12 months of progressive resistance training (PRT) on systemic inflammation, and whether reductions in systemic inflammation were associated with changes in body composition. We hypothesized that reductions in systemic inflammation following 12 months of PRT in older adults with type 2 diabetes would be associated with reductions in adiposity and increases in skeletal muscle mass.MethodsParticipants (n = 103) were randomized to receive either PRT or sham-exercise, 3 days a week for 12 months. C-reactive protein (CRP) was used to assess systemic inflammation. Skeletal muscle mass and total fat mass were determined using bioelectrical impedance.ResultsTwelve months of PRT tended to reduce CRP compared to sham exercise (β = −0.25, p = 0.087). Using linear mixed-effects models, the hypothesized relationships between body composition adaptations and CRP changes were significantly stronger for skeletal muscle mass (p = 0.04) and tended to be stronger for total fat mass (p = 0.07) following PRT when compared to sham-exercise. Using univariate regression models, stratified by group allocation, reductions in CRP were associated with increases in skeletal muscle mass (p = 0.01) and reductions in total fat mass (p = 0.02) in the PRT group, but not in the sham-exercise group (p = 0.87 and p = 0.32, respectively).ConclusionsWe have shown for the first time that reductions in systemic inflammation in older adults with type 2 diabetes following PRT were associated with increases in skeletal muscle mass. Furthermore, reductions in CRP were associated with reductions in adiposity, but only when associated with PRT. Lifestyle interventions aimed at reducing systemic inflammation in older adults with type 2 diabetes should therefore incorporate anabolic exercise such as PRT to optimize the anti-inflammatory benefits of favorable body composition adaptations.

Acute decompensated heart failure (ADHF) is associated with inflammation, oxidative stress, and excess sympathetic drive. It is unknown whether neuromodulation would improve inflammation and oxidative stress in acute heart failure. We, therefore, performed this proof-of-concept study to evaluate the effects of neuromodulation using noninvasive low-level tragus stimulation on inflammation and oxidative stress in ADHF. Nineteen patients with ejection fraction < 40% were randomized to neuromodulation 4h twice daily (6-10a.m. and 6-10p.m.) (n = 8) or sham stimulation (n = 11) during hospital admission. All patients received standard-of-care treatment. Blood samples were collected at admission and discharge. Serum cytokines were assayed using standard immunosorbent techniques. Reactive oxygen species inducibility from cultured coronary endothelial cells exposed to patient sera was determined using a dihydrodichlorofluorescein probe test (expressed as fluorescein units). Compared to sham stimulation, neuromodulation was associated with a significant reduction of circulating serum interleukin-6 levels (-78% vs. -9%; p = 0.012). Similarly, neuromodulation led to a reduction of endothelial cell oxidative stress in the neuromodulation group (1363 units to 978 units, p = 0.003) compared to sham stimulation (1146 units to 1083 units, p = 0.094). No significant differences in heart rate, blood pressure, or renal function were noted between the two groups. In this proof-of-concept pilot study, in acute decompensated heart failure, neuromodulation was feasible and safe and was associated with a reduction in systemic inflammation and attenuation of coronary endothelial cellular oxidative stress. NCT02898181.

PurposeAcute decompensated heart failure is associated with inflammation, oxidative stress, and excess sympathetic drive. It is unknown if neuromodulation would improve inflammation and oxidative stress in acute heart failure. We, therefore, performed this proof-of-concept study to evaluate the effects of neuromodulation using noninvasive low-level Tragus stimulation on inflammation and oxidative stress in ADHF.Methods19 patients with ejection fraction < 40% were randomized to neuromodulation- 4 hours twice daily (6 AM-10 AM and 6 PM-10 PM) (n = 8) or sham stimulation (n = 11) during hospital admission. All patients received standard-of-care treatment. Blood samples were collected at admission and discharge. Serum cytokines were assayed using standard immunosorbent techniques. Reactive oxygen species inducibility from cultured coronary endothelial cells exposed to patient sera was determined using dihydrodichlorofluorescein probe test (expressed as fluorescein units).ResultsCompared to sham stimulation, neuromodulation was associated with a significant reduction of circulating serum Interleukin-6 levels (−78% vs −9%; p = 0.012). Similarly, neuromodulation led to reduction of endothelial cell oxidative stress, in the neuromodulation group (1363 units to 978 units, p = 0.003) compared to sham stimulation (1146 units to 1083 units, p = 0.094). No significant difference in heart rate, blood pressure or renal function were noted between the two groups.ConclusionIn this proof-of-concept pilot study, in acute systolic heart failure, neuromodulation was feasible and safe and was associated with a reduction in systemic inflammation and attenuation of cellular oxidative stress.Clinical trial:NCT02898181

Cystic fibrosis (CF) is characterized by dietary antioxidant deficiencies, which may contribute to an oxidant-antioxidant imbalance and oxidative stress. Evaluate the effects of an oral antioxidant-enriched multivitamin supplement on antioxidant concentrations, markers of inflammation and oxidative stress, and clinical outcomes. In this investigator-initiated, multicenter, randomized, double-blind, controlled trial, 73 pancreatic-insufficient subjects with CF 10 years of age and older with an FEV1 between 40% and 100% predicted were randomized to 16 weeks of an antioxidant-enriched multivitamin or control multivitamin without antioxidant enrichment. Endpoints included systemic antioxidant concentrations, markers of inflammation and oxidative stress, clinical outcomes (pulmonary exacerbations, anthropometric measures, pulmonary function), safety, and tolerability. Change in sputum myeloperoxidase concentration over 16 weeks, the primary efficacy endpoint, was not significantly different between the treated and control groups. Systemic antioxidant (β-carotene, coenzyme Q10, γ-tocopherol, and lutein) concentrations significantly increased in the antioxidant-treated group (P < 0.001 for each), whereas circulating calprotectin and myeloperoxidase decreased in the treated group compared with the control group at Week 4. The treated group had a lower risk of first pulmonary exacerbation requiring antibiotics than the control group (adjusted hazard ratio, 0.50; P = 0.04). Lung function and growth endpoints did not differ between groups. Adverse events and tolerability were similar between groups. Antioxidant supplementation was safe and well tolerated, resulting in increased systemic antioxidant concentrations and modest reductions in systemic inflammation after 4 weeks. Antioxidant treatment was also associated with a lower risk of first pulmonary exacerbation. Clinical trial registered with www.clinicaltrials.gov (NCT01859390).

The Mediterranean diet (Med-Diet) is well known for its protective effects against noncommunicable diseases and overall mortality, thanks to its anti-inflammatory, antioxidant, and neuroprotective properties. Simultaneously, sleep is increasingly recognized as a vital modifiable factor that influences health, affecting both physiological and psychological outcomes. This narrative review summarizes epidemiological evidence on how the Med-Diet impacts sleep duration and quality, examines the biological mechanisms behind these effects, and identifies areas for future research. A comprehensive search was conducted using PubMed, Scielo, Web of Science, CrossRef, Google Scholar, and Scopus. A total of 191 articles published between 2015 and 2025 were selected based on specific inclusion and exclusion criteria. Greater adherence to the Mediterranean diet is associated with better sleep outcomes, such as longer sleep duration, shorter sleep latency, higher sleep efficiency, and a lower risk of insomnia and obstructive sleep apnea, particularly among individuals with an overweight. Mechanistically, the Med-Diet promotes better sleep through various interconnected pathways, including modulation of the tryptophan-serotonin-melatonin pathway, reduction of systemic inflammation and oxidative stress, enhancement of metabolic and cardiovascular health, protection of endothelial and brain function, and regulation of gut microbiota and circadian rhythms. Nutrients like polyphenols, omega-3 fatty acids, and fiber influence neurotransmitter balance, neuroendocrine signaling, and microbial diversity, all of which support sleep and respiratory regulation. The Med-Diet offers a promising non-pharmacological approach to improving sleep health. Further longitudinal and intervention studies are needed to establish causality, assess effects within specific populations, and explore integrated lifestyle strategies, expanding the potential for chronic disease prevention and comprehensive health promotion.

Corticobasal syndrome (CBS) is a rare tauopathy, with a complex pathophysiology that usually includes neuroinflammation. Parkinsonism, cognitive impairments, and sleep disturbances are common in CBS, although alterations in sleep architecture remain poorly characterized. Regular exercise has been recommended in CBS to manage gait dysfunction, balance issues, and cognitive decline. However, the effects of regular exercise on sleep quality, sleep architecture, and systemic inflammation in CBS remain unclear. The purpose of this study was to describe the effects of regular exercise in CBS. The design of this study was a case report. This study was conducted in an academic laboratory. An individual with CBS participated in this case study. The participant completed a 12-week multimodal training program. Cardiorespiratory fitness level was assessed with a symptom-limited cardiopulmonary exercise test and strength with a submaximal 1-repetition maximum test. Subjective and objective sleep quality were assessed using the Parkinson Disease (PD) Sleep Scale-2 and actigraphy, respectively. Sleep architecture was evaluated with polysomnography. Cognition and motor function were assessed with the Scale for Outcomes in PD-Cognition and Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS-III), respectively, functional mobility with the Time Up and Go (TUG), and fatigue with the PD Fatigue Scale. Concentrations of inflammatory markers, including interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor, and C-reactive protein, were measured from serum collected after a 12-hour fasting period. Following the training program (34 sessions; 25.35hours), improvements in fitness, objective sleep quality and architecture, cognition, TUG, and a reduction in systemic inflammation were observed. Conversely, MDS-UPDRS-III scores deteriorated, and the participant reported diminished subjective sleep quality and increased fatigue. These results, which should be interpreted with caution, suggest that various clinical outcomes improved following multimodal training. Controlled studies are warranted to confirm these observations. This is the first case report describing the effects of a training program on sleep architecture and systemic inflammation in CBS.

Obesity is a significant global health challenge, with adverse impacts on cardiometabolic health such as hypertension, dyslipidemia, and insulin resistance. One promising intervention in obesity management is intermittent fasting (PI). However, scientific evidence on the impact of IF on cardiometabolic health is still limited. This study used a scoping review design to evaluate the association between IF and cardiometabolic health in obese adults. Reference sources are available in English at least abstract between 2015–2023 as well as from PubMed and Google Scholar web sources. The search keywords on PubMed are "Adult AND intermittent fasting AND cardiometabolic" and on Google Scholar is "Intermittent fasting and cardiovascular relationships". A total of 6 articles were analyzed in this context presented in the form of tables including countries and authors, study design, participant characteristics, IF assessment on cardiometabolic states and their results. The study showed that IF methods such as Alternate Day Fasting (ADF), Time-Restricted Feeding (TRF), and the 5:2 method had different effects on cardiometabolic health. ADF is superior in weight loss, while TRF is more effective at lowering triglyceride levels. The 5:2 method showed a significant reduction in waist circumference and oxidative stress. The mechanism of IF benefits involves modulation of the gut microbiota and reduction of systemic inflammation. These results demonstrate the potential of IF as a non-pharmacological approach to manage obesity and its cardiometabolic complications. However, studies with large-scale trial designs and longer intervention durations are needed to develop standard guidelines and ensure the sustainability of IF benefits.

AB0525 GUSELKUMAB TREATMENT SHOWS RAPID ONSET OF EFFECT ON COMPONENTS OF AMERICAN COLLEGE OF RHEUMATOLOGY RESPONSE CRITERIA: RESULTS OF 2 RANDOMIZED PHASE 3 TRIALS

Introduction: Hypopharyngeal squamous cell carcinoma, stage III has poor prognosis with only 25% chance of 5 years of relative survival in such patients in spite of conventional treatment including radical surgery, radiotherapy, and concurrent chemotherapy. Case Presentation: A chronic tobacco-betel nut chewer 62-year-old male patient had dysphagia with hoarseness of voice diagnosed with stage III, grade II malignant pyriform fossa. The patient underwent 9 cycles of neoadjuvant chemotherapy with Inj Paclitaxel 100 mg and Inj Cisplatin 40 mg. He was then referred to our institute for Radical Radiotherapy with concurrent chemotherapy with adjunct Ayurvedic treatment. A total dose of 70 Gy of radiation with cobalt 60 source was administered to the bilateral face and neck, in 35 fractions. Patient also received 6 cycles of concurrent weekly chemotherapy with Inj Cisplatin 40 mg. He received well-planned adjunct Ayurvedic treatment in the form of oral Ayurvedic medicines (OAM) and detoxifying treatment, Panchakarma. All the measured adverse effects of radiotherapy such as Stomatitis, Xerostomia, Taste Alteration, Dysphagia, and Nausea were observed to be remarkably low during and post radiotherapy in this patient. Karnofsky and Quality of Life (QoL) scores revealed patient’s well-being throughout the treatment course. After 5 years, PET CT scan revealed no FDG avid locoregional recurrence or distant organ involvement implying disease-free survival (DFS). Various chemokines, cytokines, and oxidative stress markers were assessed during the course of treatment to observe tumour microenvironment. Conclusion: The present case of Head & Neck Cancer (HNC), stage III, and grade II belonged to high-grade, high-risk hypopharyngeal cancer with poor prognosis. The patient opted for Ayurvedic treatment besides radiotherapy, which continued thereafter for 5 years. We therefore emphasize that in this case, minimum side effects of radiotherapy, immunomodulation, and reduction in inflammation and oxidative stress along with good quality of life can be attributed to OAM and repeated detoxifying Panchakarma treatment supported with healthy diet and good lifestyle. The highlight of the study is the marked effect on the patient’s immune response and reduction in oxidative stress, leading to 5 years and beyond of DFS.

Obesity is associated with impaired inhibitory control and low-grade systemic inflammation. Systemic inflammation adversely affects neurocognitive performance. Here, we investigate the effects of metabolic bariatric surgery on systemic inflammation and its influence on neural mechanisms underlying inhibitory control. In a sample of 47 individuals with severe obesity, we assessed inhibitory control processing pre- and 2years post-bariatric surgery by probing neural activation and connectivity during an fMRI Stroop task. We investigated whether surgery-induced changes in plasma markers of systemic inflammation were related to changes in altered neural responses. Data were collected as part of the BARICO (Bariatric surgery Rijnstate and Radboudumc neuroimaging and Cognition in Obesity) study. Longitudinal analyses revealed decreased Stroop-related activation in the caudate nucleus and the left insula following surgery. These activation changes were accompanied by inflammation-related changes in functional coupling with medial superior frontal regions. Specifically, greater post-surgery decreases in leptin (pro-inflammatory) were associated with decreased connectivity between the anterior insula and the medial superior frontal regions, while increases in macrophage migration inhibitory factor (MIF, potentially neuroprotective) were linked to enhanced connectivity between the caudate nucleus and the medial superior frontal gyrus. Importantly, improved functional coupling between the caudate nucleus and the medial superior frontal gyrus was predictive of better task performance. Our findings suggest that surgery-induced reductions in systemic inflammation may improve inhibitory control in individuals with obesity by promoting neural changes in inflammation-sensitive brain regions and their functional interactions. This protocol was prospectively registered with the Dutch Trial Register Onderzoekmetmensen.nl, with trial number NTR29050.

Home-based transcranial static magnetic field stimulation of the motor cortex for treating levodopa-induced dyskinesias in Parkinson's disease: A randomized controlled trial

BackgroundHeterozygous variants in GBA1 are the commonest genetic risk factor for Parkinson’s disease (PD), but penetrance is incomplete. GBA1 dysfunction can cause gastrointestinal disturbances and microbiome changes in preclinical models. Mounting evidence suggests that the microbiota–gut–brain axis is potentially implicated in PD pathogenesis. Whether the gut microbiome composition is influenced by host GBA1 genetics in heterozygosis has never been explored.ObjectivesThis study aimed to evaluate whether heterozygosity for the GBA1 pathogenic L444P variant can cause perturbations in gut microbiome composition.MethodsFaecal samples collected from GBA1L444P/WT and GBA1WT/WT mice at 3 and 6 months of age were analysed through shotgun metagenomic sequencing.ResultsNo differences in α- and β-diversities were detected between genotyped groups, at either time point. Overall, we found a little variation in the gut microbiome composition and functional potential between GBA1L444P/WT and GBA1WT/WT mice over time.ConclusionHost GBA1 genotype does not impact gut microbiome structure and composition in the presented GBA1L444P/WT mouse model. Studies investigating the effect of a second hit on gut physiology and microbiome composition could explain the partial penetrance of GBA1 variants in PD.

Patients with Parkinson's disease (PD) exhibit distinct gut microbiota, which may promote gut-derived inflammation. Rifaximin is a nonabsorbable antibiotic that can modify gut microbiota. The present study investigated the effect of rifaximin on gut microbiota and inflammation status in PD. The study examined the effect of long-term rifaximin treatment on in vivo transgenic PD mice (MitoPark) and short-term rifaximin treatment on patients with PD. Rifaximin treatment caused a significant change in gut microbiota in the transgenic PD mice; in particular, it reduced the relative abundance of Prevotellaceae UCG-001 and increased the relative abundance of Bacteroides, Muribaculum, and Lachnospiraceae UCG-001. Rifaximin treatment attenuated serum interleukin-1β, interleukin-6 and tumor necrosis factor-α, claudin-5 and occludin, which indicated the reduction of systemic inflammation and the protection of the blood-brain barrier integrity. The rifaximin-treated MitoPark mice exhibited better motor and memory performance than did the control mice, with lower microglial activation and increased neuronal survival in the hippocampus. In the patients with PD, 7-day rifaximin treatment caused an increase in the relative abundance of Flavonifractor 6 months after treatment, and the change in plasma proinflammatory cytokine levels was negatively associated with the baseline plasma interleukin-1α level. In conclusion, the present study demonstrated that rifaximin exerted a neuroprotective effect on the transgenic PD mice by modulating gut microbiota. We observed that patients with higher baseline inflammation possibly benefited from rifaximin treatment. With consideration for the tolerability and safety of rifaximin, randomized controlled trials should investigate the disease-modification effect of long-term treatment on select patients with PD.

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Treatment of people at ultra-high risk for psychosis.