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Cellular and Molecular Neurobiology Aug 2023Parkinson's disease (PD) is one of the most common degenerative brain disorders caused by the loss of dopaminergic neurons in the substantia nigra (SN). Lewy bodies and... (Review)
Review
Parkinson's disease (PD) is one of the most common degenerative brain disorders caused by the loss of dopaminergic neurons in the substantia nigra (SN). Lewy bodies and -synuclein accumulation in the SN are hallmarks of the neuropathology of PD. Due to lifestyle changes and prolonged L-dopa administration, patients with PD frequently have vitamin deficiencies, especially folate, vitamin B6, and vitamin B12. These disorders augment circulating levels of Homocysteine with the development of hyperhomocysteinemia, which may contribute to the pathogenesis of PD. Therefore, this review aimed to ascertain if hyperhomocysteinemia may play a part in oxidative and inflammatory signaling pathways that contribute to PD development. Hyperhomocysteinemia is implicated in the pathogenesis of neurodegenerative disorders, including PD. Hyperhomocysteinemia triggers the development and progression of PD by different mechanisms, including oxidative stress, mitochondrial dysfunction, apoptosis, and endothelial dysfunction. Particularly, the progression of PD is linked with high inflammatory changes and systemic inflammatory disorders. Hyperhomocysteinemia induces immune activation and oxidative stress. In turn, activated immune response promotes the development and progression of hyperhomocysteinemia. Therefore, hyperhomocysteinemia-induced immunoinflammatory disorders and abnormal immune response may aggravate abnormal immunoinflammatory in PD, leading to more progression of PD severity. Also, inflammatory signaling pathways like nuclear factor kappa B (NF-κB) and nod-like receptor pyrin 3 (NLRP3) inflammasome and other signaling pathways are intricate in the pathogenesis of PD. In conclusion, hyperhomocysteinemia is involved in the development and progression of PD neuropathology either directly via induction degeneration of dopaminergic neurons or indirectly via activation of inflammatory signaling pathways.
Topics: Humans; Parkinson Disease; Hyperhomocysteinemia; Levodopa; Substantia Nigra; Neurodegenerative Diseases; Dopaminergic Neurons
PubMed: 37074484
DOI: 10.1007/s10571-023-01350-8 -
Photochemical & Photobiological... Oct 2023The present study investigates the efficacy of Photobiomodulation (PBM) and Vitamin B Complex (VBC) to relieve pain, both in separately and combined (PBM and VBC).
PURPOSE
The present study investigates the efficacy of Photobiomodulation (PBM) and Vitamin B Complex (VBC) to relieve pain, both in separately and combined (PBM and VBC).
METHODS
Rats with chronic constriction injury of the right infraorbital nerve (CCI-IoN) or Sham surgery were used. PBM was administered at a wavelength of 904 nm and energy density of 6.23 J/cm and VBC (containing B1, B6 and B12) subcutaneously, both separately and combined. Behavioral tests were performed to assess mechanical and thermal hypersensitivity before and after CCI and after PBM, VBC, or PBM + VBC. The expression of inflammatory proteins in the trigeminal ganglion and the immunohistochemical alterations of Periaqueductal Gray (PAG) astrocytes and microglia were examined following CCI and treatments.
RESULTS
All testeds treatments reversed the painful behavior. The decrease in pain was accompanied by a decrease of Glial Fibrillary Acidic Protein (GFAP), a specific astrocytic marker, and Ionized calcium-binding adaptor molecule 1 (Iba-1), a marker of microglia, and decreased expression of Transient Receptor Potential Vanilloid 1 (TRPV1), Substance P, and Calcitonin Gene-Related Peptide (CGRP) induced by CCI-IoN in PAG and Trigeminal ganglion. Furthermore, both treatments showed a higher expression of Cannabinoid-type 1 (CB1) receptor in the trigeminal ganglion compared to CCI-IoN rats. Our results show that no difference was observed between groups.
CONCLUSION
We showed that PBM or VBC regulates neuroinflammation and reduces inflammatory protein expression. However, the combination of PBM and VBC did not enhance the effectiveness of both therapies alone.
Topics: Rats; Animals; Vitamin B Complex; Rats, Sprague-Dawley; Facial Pain
PubMed: 37340216
DOI: 10.1007/s43630-023-00452-y -
Nutrition Research (New York, N.Y.) Jan 2024Previous studies have shown that B vitamins can relieve migraine. However, the association between vitamin B and folate, 2 important B vitamins consumed in the diet,...
Previous studies have shown that B vitamins can relieve migraine. However, the association between vitamin B and folate, 2 important B vitamins consumed in the diet, with migraine have received minimal attention. This study explored the independent relationships between dietary vitamin B and folate intake with migraine and the interaction effect of these 2 nutrients on migraine in US adults. We hypothesized that vitamin B and folate intake would be inversely associated with migraine. This study included cross-sectional data from participants aged 20 years and older who participated in the National Health and Nutrition Examination Survey from 1999 to 2004. We conducted multivariate logistic regression and restricted cubic spline regression to explore the association between dietary vitamin B and folate intake on migraine. Also, relative excess risk due to interaction, attributable proportion of interaction, and synergy index were used to assess additive interactions. A total of 7017 participants were included in this study, 1350 of whom were migraineurs. We determined that vitamin B and folate intake revealed a negative association with severe headache or migraine (0.66; 95% confidence interval [CI], 0.47-0.89; P = .01 and 0.57; 95% CI, 0.42-0.78; P = .002]), respectively. Also, a significant interaction effect between a high mass of vitamin B and folate intake was observed for a lower risk of migraine (relative excess risk due to interaction, 0.28 [95% CI, 0.05-0.51]; attributable proportion of interaction: 0.45 [95% CI, 0.05-0.86]; synergy index: 0.58 [95% CI, 0.40-0.83]). A high mass of vitamin B and folate intake (vitamin B intake ≥ 2.39 mg/day and folate intake ≥ 502.01 µg/day) presented a synergistic interaction with migraine, suggesting that these 2 nutrients might be beneficial in preventing migraine.
Topics: Adult; Humans; Folic Acid; Vitamin B 6; Vitamin B Complex; Nutrition Surveys; Cross-Sectional Studies; Vitamin B 12; Pyridoxine; Logistic Models; Headache
PubMed: 38042023
DOI: 10.1016/j.nutres.2023.11.008 -
Diabetology & Metabolic Syndrome Oct 2023The available evidence regarding the association of antioxidants, minerals, and vitamins with the risk of metabolic syndrome (MetS) traits is currently limited and...
BACKGROUND
The available evidence regarding the association of antioxidants, minerals, and vitamins with the risk of metabolic syndrome (MetS) traits is currently limited and inconsistent. Therefore, the purpose of this Mendelian randomization (MR) study was to investigate the potential causal relationship between genetically predicted antioxidants, minerals, and vitamins, and MetS.
METHODS
In this study, we utilized genetic variation as instrumental variable (IV) to capture exposure data related to commonly consumed dietary nutrients, including antioxidants (β-carotene, lycopene, and uric acid), minerals (copper, calcium, iron, magnesium, phosphorus, zinc, and selenium), and vitamins (folate, vitamin A, B6, B12, C, D, E, and K1). The outcomes of interest, namely MetS (n = 291,107), waist circumference (n = 462,166), hypertension (n = 463,010), fasting blood glucose (FBG) (n = 281,416), triglycerides (n = 441,016), and high-density lipoprotein cholesterol (HDL-C) (n = 403,943), were assessed using pooled data obtained from the most comprehensive genome-wide association study (GWAS) available. Finally, we applied the inverse variance weighting method as the result and conducted a sensitivity analysis for further validation.
RESULTS
Genetically predicted higher iron (OR = 1.070, 95% CI 1.037-1.105, P = 2.91E-05) and magnesium levels (OR = 1.130, 95% CI 1.058-1.208, P = 2.80E-04) were positively associated with increased risk of MetS. For each component of MetS, higher level of genetically predicted selenium (OR = 0.971, 95% CI 0.957-0.986, P = 1.09E-04) was negatively correlated with HDL-C levels, while vitamin K1 (OR = 1.023, 95% CI 1.012-1.033, P = 2.90E-05) was positively correlated with HDL-C levels. Moreover, genetically predicted vitamin D (OR = 0.985, 95% CI 0.978-0.992, P = 5.51E-5) had a protective effect on FBG levels. Genetically predicted iron level (OR = 1.043, 95% CI 1.022-1.064, P = 4.33E-05) had a risk effect on TG level.
CONCLUSIONS
Our study provides evidence that genetically predicted some specific, but not all, antioxidants, minerals, and vitamins may be causally related to the development of MetS traits.
PubMed: 37817280
DOI: 10.1186/s13098-023-01174-y -
Frontiers in Nutrition 2024This study investigated the efficacy of a mixed beet-based supplement (BEET) versus placebo (PL) in countering inflammation during recovery from 2.25 h of intensive...
OBJECTIVES
This study investigated the efficacy of a mixed beet-based supplement (BEET) versus placebo (PL) in countering inflammation during recovery from 2.25 h of intensive cycling in 20 male and female cyclists. A multi-omics approach was used that included untargeted proteomics and a targeted oxylipin panel.
METHODS
A randomized, placebo-controlled, double-blind, crossover design was used with two 2-week supplementation periods and a 2-week washout period. Supplementation periods were followed by a 2.25 h cycling bout at close to 70%VO. The BEET supplement provided 212 mg of nitrates per day, 200 mg caffeine from green tea extract, 44 mg vitamin C from Camu Camu berry, B-vitamins from quinoa sprouts (40% Daily Value for thiamin, riboflavin, niacin, and vitamin B6), and 2.5 g of a mushroom blend containing Cordyceps sinensis and Inonotus obliquus. Six blood samples were collected before and after supplementation (overnight fasted state), immediately post-exercise, and at 1.5 h-, 3 h-, and 24 h-post-exercise.
RESULTS
The 2.25 h cycling bout increased plasma levels of 41 of 67 oxylipins detected. BEET supplementation significantly increased plasma nitrate (NO ) and nitrite (NO ) (sum, NO + NO ) concentrations (interaction effect, < 0.001) and two anti-inflammatory oxylipins [18-hydroxyeicosapentaenoic acid (18-HEPE) and 4-hydroxy-docosahexanoic acid (4-HDoHE)]. The untargeted proteomics analysis identified 616 proteins (458 across all times points), and 2-way ANOVA revealed a cluster of 45 proteins that were decreased and a cluster of 21 that were increased in the BEET versus PL trials. Functional enrichment supported significant BEET-related reductions in inflammation-related proteins including several proteins related to complement activation, the acute phase response, and immune cell adhesion, migration, and differentiation.
DISCUSSION
Intake of a BEET-based supplement during a 2-week period was linked to higher plasma levels of NO + NO , elevated post-exercise levels of two anti-inflammatory oxylipins, and a significant decrease in a cluster of proteins involved in complement activation and inflammation. These data support that 2-weeks intake of nitrate from a mixed beet-based supplement moderated protein biomarkers of exercise-induced inflammation in athletes.
PubMed: 38873567
DOI: 10.3389/fnut.2024.1408804 -
Nutrients Jul 2023Micronutrition in pregnancy is critical to impact not only fetal growth and development but also long-term physical and psychiatric health outcomes. (Clinical Trial)
Clinical Trial
BACKGROUND
Micronutrition in pregnancy is critical to impact not only fetal growth and development but also long-term physical and psychiatric health outcomes.
OBJECTIVE
Estimate micronutrient intake from food and dietary supplements in a diverse cohort of pregnant women and compare intake to the Dietary Reference Intakes (DRIs).
DESIGN
Secondary analysis of women enrolled in a multi-site clinical trial of docosahexaenoic acid (DHA) supplementation who provided their dietary intake using the diet history questionnaire-II ( = 843) or multiple 24 h recalls ( = 178) at baseline and their intake of nutritional supplements at baseline through 30 days postpartum.
PARTICIPANTS/SETTING
1021 participants from the parent trial who had reliable data for dietary intake, supplement intake, or both.
MAIN OUTCOME MEASURES
Micronutrient intake from dietary and supplement sources and percentage of intakes meeting the DRIs for pregnancy.
STATISTICAL ANALYSES PERFORMED
Percent of participants whose intake was below the estimated average requirement (EAR) or adequate intake (AI) and above the tolerable upper limit (UL).
RESULTS
Dietary intakes of choline, folate, iron, vitamin D, zinc, vitamin E, magnesium, and potassium, were below the AI or EAR for 30-91% of the participants; thiamin and vitamin B6 were also below the AI or EAR for non-Hispanic/Latina women. Supplement intake improved the intake for most; however, 80% of the group remained below the AI for choline and 52.5% for potassium while 30% remained below the EAR for magnesium. Folate and iron intakes were above the UL for 80% and 19%, respectively.
CONCLUSIONS
Dietary supplements, despite their variability, allowed the majority of this cohort of pregnant women to achieve adequate intakes for most micronutrients. Choline, magnesium, and potassium were exceptions. Of interest, folate intake was above the tolerable UL for the majority and iron for 16.8% of the participants. Clinicians have the opportunity to address the most common nutrient deficits and limits with advice on food sources that provide choline, magnesium, and potassium and to ensure folate is not overabundant. More research is needed to determine if these findings are similar in a cross-sectional population.
Topics: Female; Humans; Pregnancy; Choline; Cross-Sectional Studies; Diet; Dietary Supplements; Folic Acid; Iron; Magnesium; Micronutrients; Nutritional Requirements; Potassium; Pregnant Women; Trace Elements
PubMed: 37513643
DOI: 10.3390/nu15143228 -
Frontiers in Public Health 2024This study aims to understand the impact of dietary intake through supplementation of vitamins D, B6, and magnesium on elevated depressive symptoms, a mental health...
OBJECTIVE
This study aims to understand the impact of dietary intake through supplementation of vitamins D, B6, and magnesium on elevated depressive symptoms, a mental health illness that is a leading contributor to global disability and a public health concern.
METHODS
Multiple datasets from the National Health and Nutrition Examination Survey 2017-March 2020 investigated the associations between vitamin D, B6, and magnesium on depression screening scores. A cross-sectional sample of adults over 20 was extracted ( = 9,232). Chi-square tests and logistic regression analyses were used to investigate the associations.
RESULTS
Individuals with low amounts of vitamin D ( = 0.0481) were more likely to report elevated depressive symptoms relative to those with low amounts of vitamin B6 ( = 0.0225). These results remained significant among those with high magnesium ( = 0.0133) proportionate to high vitamin B6 ( = 0.0225). In the age-adjusted model, a lower intake of vitamin D, vitamin B6, and magnesium showed a relationship with elevated depressive symptoms (Vitamin D: OR = 0.611, 95% CI 0.382-0.980 Vitamin B6: OR = 0.503, 95% CI 0.291-0.867 Magnesium: OR = 0.458, 95% CI 0.277-0.759). The fully adjusted regression model (gender, race/ethnicity, and household food security) showed that a lower intake of vitamin B6 and magnesium correlated with elevated depressive symptoms (Vitamin B6: OR = 0.439, 95% CI 0.260-0.738 Magnesium: OR = 0.465, 95% CI 0.303-0.714).
CONCLUSION
Preventive measures could be addressed by identifying the risks of vitamin deficiencies. Further epidemiological research is needed for the individual effects of vitamin supplementation and depression screening scores. Future prospective cohort studies exploring these associations, focusing on daily dietary intake, are needed to validate the direction of causation further and understand the underlying mechanisms.
Topics: Adult; Humans; Magnesium; Vitamin B 6; Vitamin D; Depression; Dietary Supplements; Prospective Studies; Cross-Sectional Studies; Nutrition Surveys; Public Health; Vitamins; Eating
PubMed: 38605872
DOI: 10.3389/fpubh.2024.1369666 -
Nature Communications Nov 2023Mucosal-associated invariant T (MAIT) cells have been implicated in various inflammatory diseases of barrier organs, but so far, their role in kidney disease is unclear....
Mucosal-associated invariant T (MAIT) cells have been implicated in various inflammatory diseases of barrier organs, but so far, their role in kidney disease is unclear. Here we report that MAIT cells that recognize their prototypical ligand, the vitamin B2 intermediate 5-OP-RU presented by MR1, reside in human and mouse kidneys. Single cell RNAseq analysis reveals several intrarenal MAIT subsets, and one, carrying the genetic fingerprint of tissue-resident MAIT17 cells, is activated and expanded in a murine model of crescentic glomerulonephritis (cGN). An equivalent subset is also present in kidney biopsies of patients with anti-neutrophil cytoplasmatic antibody (ANCA)-associated cGN. MAIT cell-deficient MR1 mice show aggravated disease, whereas B6-MAIT mice, harboring higher MAIT cell numbers, are protected from cGN. The expanded MAIT17 cells express anti-inflammatory mediators known to suppress cGN, such as CTLA-4, PD-1, and TGF-β. Interactome analysis predicts CXCR6 - CXCL16-mediated cross-talk with renal mononuclear phagocytes, known to drive cGN progression. In line, we find that cGN is aggravated upon CXCL16 blockade. Finally, we present an optimized 5-OP-RU synthesis method which we apply to attenuating cGN in mice. In summary, we propose that CXCR6 MAIT cells might play a protective role in cGN, implicating them as a potential target for anti-inflammatory therapies.
Topics: Humans; Animals; Mice; Mucosal-Associated Invariant T Cells; Myeloid Cells; Kidney Diseases; Anti-Inflammatory Agents; Histocompatibility Antigens Class I
PubMed: 37968302
DOI: 10.1038/s41467-023-43269-0 -
Endocrine Practice : Official Journal... Aug 2023One of the most frequently occurring complications of diabetes mellitus is peripheral neuropathy. Despite the painful symptoms associated with diabetic peripheral... (Review)
Review
OBJECTIVE
One of the most frequently occurring complications of diabetes mellitus is peripheral neuropathy. Despite the painful symptoms associated with diabetic peripheral neuropathy (DPN), the current treatment landscape focuses on managing symptoms without addressing the underlying causes of DPN. This narrative review describes the mechanistic effects and clinical trial data supporting the use of L-methylfolate calcium (LMF), the bioactive form of folate, which is available in the United States as a prescription medical food that also contains other B vitamins for the dietary management of DPN.
METHODS
Preclinical and clinical trial data evaluating the impact of LMF on DPN were identified using PubMed searches for articles published between 2010 and 2023. Search terms included: folate, LMF, diabetes, neuropathy, and neuropathic pain. Additionally, a literature search was conducted to identify studies related to LMF, genetic polymorphisms, and DPN pathophysiology.
RESULTS
Several studies show that the C677T variant of the methylenetetrahydrofolate reductase gene is linked to greater risk of DPN than other methylenetetrahydrofolate reductase variants due to its inhibitory effects on several folic acid metabolic pathways. One double-blind, randomized controlled trial, 5 open-label studies, and 1 retrospective study found that LMF has a significant beneficial effect on DPN that extends beyond symptomatic relief to include modulating the underlying pathophysiology that leads to the progression and symptoms of DPN. LMF also significantly improves patient quality of life, with minimal adverse effects.
CONCLUSION
Preclinical and clinical studies have found that LMF can be used to treat the underlying causes of DPN and provide long-lasting symptomatic relief.
Topics: Humans; Diabetic Neuropathies; Diabetes Mellitus, Type 2; Methylenetetrahydrofolate Reductase (NADPH2); Quality of Life; Retrospective Studies; Folic Acid; Randomized Controlled Trials as Topic
PubMed: 37088147
DOI: 10.1016/j.eprac.2023.04.005 -
Journal of Affective Disorders Jan 2024The use of adjunctive therapy for bipolar disorder is increasingly considered to increase the efficacy of standard treatments. In this randomized clinical trial, we... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The use of adjunctive therapy for bipolar disorder is increasingly considered to increase the efficacy of standard treatments. In this randomized clinical trial, we evaluated the effect of vitamins B1 and B6 in separate treatment arms on mood symptoms, cognitive status, and sleep quality in hospitalized patients with bipolar disorder in manic episodes.
METHOD
In addition to receiving standard lithium treatment, participants (N = 66) were randomized to one of three conditions: 100 mg of vitamin B1, 40 mg of vitamin B6, or placebo. Outcomes were assessed one and 8 weeks of daily treatment, including the Young Mania Rating Scale (YMRS), Pittsburgh Sleep Quality Scale (PSQI), and Mini-Mental State Examination (MMSE). This study was performed between December 2020 and September 2021 based on the registration code number IRCT20200307046712N1.
RESULTS
Vitamin B6 had a significant effect (P value < 0.025 as significant) on mood improvement compared to placebo (F (1, 27.42) = 30.25, P < 0.001, r = 0.72), but vitamin B1 had no significant effect on mood improvement compared to Placebo (F (1/35.68) = 4.76, P = 0.036, r = 0.34). The contrasts between groups on PSQI showed a significant effect (P value < 0.025 as significant) of vitamin B6 over placebo for sleep status improvement (F (1/32.91) = 16.24, P < 0.001, r = 0.57) and also a significant effect of vitamin B1 over placebo (F (1/41.21) = 13.32, P < 0.001, r = 0.49).
CONCLUSIONS
The use of vitamin B6 as an adjunctive therapy to lithium can be associated with the improvement of mood symptoms in patients with bipolar disorder in the midst of a manic episode.
Topics: Humans; Bipolar Disorder; Lithium; Thiamine; Drug Therapy, Combination; Vitamin B 6; Vitamins; Double-Blind Method; Treatment Outcome; Antimanic Agents; Antipsychotic Agents
PubMed: 37866735
DOI: 10.1016/j.jad.2023.10.121