Combined probiotics with vitamin D3 supplementation improved aerobic performance and gut microbiome composition in mixed martial arts athletes.

Introduction: Mixed Martial Arts (MMA) is characterized as an interval sport in which the training program focuses on enhancing both aerobic and anaerobic capacities. Therefore, strategies targeting the intestinal microbiome may be beneficial for MMA athletes. Moreover, vitamin D supplementation may amplify the positive effects of certain bacterial strains. We previously demonstrated that the combined of probiotics and vitamin D3 supplementation improved the lactate utilization ratio, total work, and average power achieved during anaerobic tests in MMA. Therefore, this study aimed to investigate whether combined probiotic and vitamin D3 ingestion can modify the composition of the gut microbiome and epithelial cell permeability, influence the inflammatory response, and ultimately enhance aerobic capacity. Methods: A 4-week clinical trial was conducted with 23 male MMA athletes randomly assigned to either the probiotic + vitamin D3 (PRO + VIT D) group or the vitamin D3 group (VIT D). The trial employed a double-blind, placebo-controlled design and involved measurements of serum inflammatory markers, gut microbiome composition, epithelial cell permeability, and aerobic performance. Results: After 4-week of supplementation, we found a significantly lower concentration of calprotectin in the PRO + VIT D group (34.79 ± 24.38 mmol/L) compared to the value before (69.50 ± 46.91) supplementation (p = 0.030), augmentation of beta diversity after the intervention in the PRO + VIT D group (p = 0.0005) and an extended time to exhaustion to 559.00 ± 68.99; compared to the value before (496.30 ± 89.98; p = 0.023) after combined probiotic and vitamin D3 supplementation in MMA athletes. No effect was observed in the VIT D group. Conclusion: Our results indicate that combined treatment of probiotics and vitamin D3 may cause alterations in alpha and beta diversity and the composition of the gut microbiota in MMA athletes. We observed an improvement in epithelial cell permeability and an extended time to exhaustion during exercise in MMA athletes following a 4-week combined probiotic and vitamin D3 treatment.

Impact of 12 Weeks of Vitamin D3 Administration in Parkinson's Patients with Deep Brain Stimulation on Kynurenine Pathway and Inflammatory Status.

The current study aimed to investigate whether a 12-week Body Mass Index (BMI)-based (the higher the BMI, the higher the dosage) vitamin D3 administration may affect both the kynurenine pathway (KP) and the inflammatory state in Parkinson's disease (PD) patients with deep brain stimulation (DBS) and may be useful for developing novel therapeutic targets against PD. Patients were randomly assigned to two groups: supplemented with vitamin D3 (VitD, n = 15) and treated with vegetable oil (PL, n = 21). Administration lasted for 12 weeks. The isotope dilution method by LC-MS/MS was applied to measure KP and vitamin D metabolites. Serum concentrations of cytokines such as IL-6 and TNF-α were measured using ELISA kits. After administration, the serum concentration of TNF-α decreased in PD patients with DBS. Moreover, in KP: 3-hydroksykynurenine (3-HK) was increased in the PL group, picolinic acid was decreased in the PL group, and kynurenic acid tended to be higher after administration. Furthermore, a negative correlation between 3-HK and 25(OH)D3 and 24,25(OH)2D3 was noticed. Our preliminary results provide further evidence regarding a key link between the KP substances, inflammation status, and metabolites of vitamin D in PD patients with DBS. These findings may reflect the neuroprotective abilities of vitamin D3 in PD patients with DBS.

Supplementation with Vitamin D3 Protects against Mitochondrial Dysfunction and Loss of BDNF-Mediated Akt Activity in the Hippocampus during Long-Term Dexamethasone Treatment in Rats.

Dexamethasone (DEXA) is a commonly used steroid drug with immunosuppressive and analgesic properties. Unfortunately, long-term exposure to DEXA severely impairs brain function. This study aimed to investigate the effects of vitamin D3 supplementation during chronic DEXA treatment on neurogenesis, mitochondrial energy metabolism, protein levels involved in the BDNF-mediated Akt activity, and specific receptors in the hippocampus. We found reduced serum concentrations of 25-hydroxyvitamin D3 (25(OH)D3), downregulated proBDNF and pAkt, dysregulated glucocorticosteroid and mineralocorticoid receptors, impaired mitochondrial biogenesis, and dysfunctional mitochondria energy metabolism in the DEXA-treated group. In contrast, supplementation with vitamin D3 restored the 25(OH)D3 concentration to a value close to that of the control group. There was an elevation in neurotrophic factor protein level, along with augmented activity of pAkt and increased citrate synthase activity in the hippocampus after vitamin D3 administration in long-term DEXA-treated rats. Our findings demonstrate that vitamin D3 supplementation plays a protective role in the hippocampus and partially mitigates the deleterious effects of long-term DEXA administration. The association between serum 25(OH)D3 concentration and BDNF level in the hippocampus indicates the importance of applying vitamin D3 supplementation to prevent and treat pathological conditions.

Effect of 12-Week BMI-Based Vitamin D3 Supplementation in Parkinson's Disease with Deep Brain Stimulation on Physical Performance, Inflammation, and Vitamin D Metabolites.

Parkinson's disease (PD) is the second most common neurodegenerative disease. To manage motor symptoms not controlled adequately with medication, deep brain stimulation (DBS) is used. PD patients often manifest vitamin D deficiency, which may be connected with a higher risk of falls. We administered a 12-week vitamin D3 supplementation based on BMI (with higher doses given to patients with higher BMI) to investigate its effects on physical performance and inflammation status in PD patients with DBS. Patients were randomly divided into two groups: treated with vitamin D3 (VitD, n = 13), and supplemented with vegetable oil as the placebo group (PL, n = 16). Patients underwent functional tests to assess their physical performance three times during this study. The serum 25(OH)D3 concentration increased to the recommended level of 30 ng/mL in the VitD group, and a significant elevation in vitamin D metabolites in this group was found. We observed significant improvement in the Up and Go and the 6 MWT in the VitD group. In inflammation status, we noticed a trend toward a decrease in the VitD group. To conclude, achieving the optimal serum 25(OH)D3 concentration is associated with better functional test performance and consequently may have a positive impact on reducing falling risk in PD.

Effects of Probiotics and Vitamin D3 Supplementation on Sports Performance Markers in Male Mixed Martial Arts Athletes: A Randomized Trial.

BACKGROUND: Strategies targeted at the intestine microbiome seem to be beneficial for professional athletes. The gut-muscle axis is associated with the inflammatory state, glucose metabolism, mitochondrial function, and central nervous system health. All these mechanisms may affect maximal oxygen uptake, muscle strength, and training adaptation. Moreover, the positive effect of certain bacterial strains may be enhanced by vitamin D. Thus, this study aimed to assess and compare the level of selected markers of sports performance of mixed martial arts (MMA) athletes supplemented with vitamin D3 or probiotics combined with vitamin D3. METHODS: A 4-week randomized double-blind placebo-controlled clinical trial was conducted with 23 MMA male athletes assigned to the vitamin D3 group (Vit D; n = 12) or probiotics + vitamin D3 group (PRO + VitD; n = 11). Repeated measures of the creatine kinase level, lactate utilization ratio, and anaerobic performance were conducted. RESULTS: After 4 weeks of supplementation, we found lower lactate concentrations 60 min after the acute sprint interval in the PRO + VitD group when compared to the Vit D group (4.73 ± 1.62 and 5.88 ± 1.55 mmol/L; p < 0.05). In addition, the intervention improved the total work (232.00 ± 14.06 and 240.72 ± 13.38 J kg-1; p < 0.05), and mean power following the anaerobic exercise protocol (7.73 ± 0.47 and 8.02 ± 0.45 W kg-1; p < 0.05) only in the PRO + VitD group. Moreover, there was an improvement in the lactate utilization ratio in the PRO + VitD group compared with the Vit D group as shown by the percentage of T60/T3 ratio (73.6 ± 6.9 and 65.1 ± 9.9%, respectively; p < 0.05). We also observed elevated serum 25(OH)D3 concentrations after acute sprint interval exercise in both groups, however, there were no significant differences between the groups. CONCLUSION: Four weeks of combined probiotic and vitamin D3 supplementation enhanced lactate utilization and beneficially affected anaerobic performance in MMA athletes.

Changes in selected exerkines concentration post folk-dance training are accompanied by glucose homeostasis and physical performance improvement in older adults.

The study aimed to evaluate the impact of selected exerkines concentration induced by folk-dance and balance training on physical performance, insulin resistance, and blood pressure in older adults. Participants (n = 41, age 71.3 ± 5.5 years) were randomly assigned to folk-dance (DG), balance training (BG), or control group (CG). The training was performed 3 times a week for 12 weeks. Physical performance tests-time up and go (TUG) and 6-min walk test (6MWT), blood pressure, insulin resistance, and selected proteins induced by exercise (exerkines) were assessed at baseline and post-exercise intervention. Significant improvement in TUG (p = 0.006 for BG and 0.039 for DG) and 6MWT tests (in BG and DG p = 0.001), reduction of systolic blood pressure (p = 0.001 for BG and 0.003 for DG), and diastolic blood pressure (for BG; p = 0.001) were registered post-intervention. These positive changes were accompanied by the drop in brain-derived neurotrophic factor (p = 0.002 for BG and 0.002 for DG), the increase of irisin concentration (p = 0.029 for BG and 0.022 for DG) in both groups, and DG the amelioration of insulin resistance indicators (HOMA-IR p = 0.023 and QUICKI p = 0.035). Folk-dance training significantly reduced the c-terminal agrin fragment (CAF; p = 0.024). Obtained data indicated that both training programs effectively improved physical performance and blood pressure, accompanied by changes in selected exerkines. Still, folk-dance had enhanced insulin sensitivity.

12 Weeks of Physical Exercise Attenuates Oxidative Stress, Improves Functional Tests Performance, and Reduces Fall Risk in Elderly Women Independently on Serum 25(OH)D Concentration.

The study aimed to evaluate if the 25(OH)D concentration is related to physical training responses. Moreover, to determine the association between serum 25(OH)D concentration and older women's physical performance, oxidative stress markers, inflammation, and bone metabolism. 37 older women (age 72.9 ± 5.2 years) were assigned into two groups: supplemented (SG) and non-supplemented (NSG). Then, the participants from SG and NSG were randomly assigned into exercised and non-exercised groups: exercise sufficient vitamin D group (ESD; n = 10), exercise insufficient vitamin D group (EID; n = 9), control sufficient vitamin D group (CSD; n = 9), and control insufficient vitamin D group (CID; n = 9). To assess the study aims time up and go test (TUG), 6 min walk test (6MWT), fall risk test (FRT), blood osteocalcin (OC), parathormone (PTH), calcium (Ca2+), sulfhydryl groups (SH), malondialdehyde (MDA), and interleukin-6 (IL-6) were performed. The results showed that a higher 25(OH)D concentration was in line with better physical performance and bone metabolism as well as lower inflammation. After 12 weeks of training we noted an improvement in 6MWT (from 374.0 ± 17.3 to 415.0 ± 18.8; p = 0.001 and from 364.8 ± 32.8 to 419.4 ± 32.3; p = 0.001 for EID and ESD, respectively), TUG (from 7.9 ± 0.5 to 6.8 ± 0.8; p = 0.001 and from 7.3 ± 1.5 to 6.4 ± 0.9; p = 0.002, for EID and ESD, respectively), reduction of fall risk (from 2.8 ± 0.8 to 1.9 ± 0.4; p = 0.003 and from 2.1 ± 1.1 to 1.6 ± 0.5; p = 0.047, for EID and ESD, respectively) and increase in SH groups (from 0.53 ± 0.06 to 0.58 ± 0.08; p = 0.012 and from 0.54 ± 0.03 to 0.59 ± 0.04; p = 0.005, for EID and ESD, respectively), regardless of the baseline 25(OH)D concentration. A decrease in PTH and OC concentration was observed only in EID group (from 57.7 ± 15.7 to 49.4 ± 12.6; p = 0.013 for PTH and from 27.9 ± 17.2 to 18.0 ± 6.2; p = 0.004 for OC). To conclude, vitamin D concentration among older women is associated with physical performance, fall risk, inflammation, and bone metabolism markers. Moreover, 12 weeks of training improved physical performance and antioxidant protection, regardless of baseline vitamin D concentration.

Single bout of exercise triggers the increase of vitamin D blood concentration in adolescent trained boys: a pilot study.

Vitamin D is necessary for musculoskeletal health, however, the supplementation of vitamin D above the sufficiency level does not bring additional bone mass density (BMD), unlike physical exercise which enhances the bone formatting process. Regular physical activity has been shown to upregulate VDR expression in muscles and to increase circulating vitamin D. Here we investigate whether a single bout of exercise might change 25(OH)D3 blood concentration and how it affects metabolic response to exercise. Twenty-six boys, 13.8 years old (SD ± 0.7) soccer players, participated in the study. The participants performed one of two types of exercise: the first group performed the VO2max test until exhaustion, and the second performed three times the repeated 30 s Wingate Anaerobic Test (WAnT). Blood was collected before, 15 min and one hour after the exercise. The concentration of 25(OH)D3, parathyroid hormone (PTH), interleukin-6 (IL-6), lactate, non-esterified fatty acids (NEFA) and glycerol were determined. 25(OH)D3 concentration significantly increased after the exercise in all boys. The most prominent changes in 25(OH)D3, observed after WAnT, were associated with the rise of PTH. The dimensions of response to the exercises observed through the changes in the concentration of 25(OH)D3, PTH, NEFA and glycerol were associated with the significant increases of IL-6 level. A single bout of exercise may increase the serum's 25(OH)D3 concentration in young trained boys. The intensive interval exercise brings a more potent stimulus to vitamin D fluctuations in young organisms. Our results support the hypothesis that muscles may both store and release 25(OH)D3.

The Proper Diet and Regular Physical Activity Slow Down the Development of Parkinson Disease.

From year to year, we know more about neurodegeneration and Parkinson's disease (PD). A positive influence of various types of physical activity is more often described in the context of neuroprotection and prevention as well as the form of rehabilitation in Parkinson's patients. Moreover, when we look at supplementation, clinical nutrition and dietetics, we will see that balancing consumed products and supplementing the vitamins or minerals is necessary. Considering the biochemical pathways in skeletal muscle, we may see that many researchers desire to identify molecular mediators that have an impact through exercise and balanced diet on human health or development of the neurodegenerative disease. Therefore, it is mandatory to study the potential mechanism(s) related to diet and factors resulted from physical activity as molecular mediators, which play a therapeutic role in PD. This review summarizes the available literature on mechanisms and specific pathways involved in diet-exercise relationship and discusses how therapy, including appropriate exercises and diet that influence molecular mediators, may significantly slow down the progress of neurodegenerative processes. We suggest that a proper diet combined with physical activity will be a good solution for psycho-muscle BALANCE not only in PD but also in other neurodegenerative diseases.

The Positive Impact of Vitamin D on Glucocorticoid-Dependent Skeletal Muscle Atrophy.

(1) The study aimed to investigate whether vitamin D3 supplementation would positively affect rats with glucocorticoids-induced muscle atrophy as measured by skeletal muscle mass in two experimental conditions: chronic dexamethasone (DEX) administration and a model of the chronic stress response. (2) The study lasted 28 consecutive days and was performed on 45 male Wistar rats randomly divided into six groups. These included two groups treated by abdominal injection of DEX at a dose of 2 mg/kg/day supplemented with vegetable oil (DEX PL; n = 7) or with vitamin D3 600 IU/kg/day (DEX SUP; n = 8), respectively, and a control group treated with an abdominal injection of saline (CON; n = 6). In addition, there were two groups of rats chronically stressed by cold water immersion (1 hour/day in a glass box with 1-cm-deep ice/water mixture; temperature ~4 °C), which were supplemented with vegetable oil as a placebo (STR PL; n = 9) or vitamin D3 at 600 IU/kg/day (STR SUP; n = 9). The last group was of sham-stressed rats (SHM; n = 6). Blood, soleus, extensor digitorum longus, gastrocnemius, tibialis anterior, and quadriceps femoris muscles were collected and weighed. The heart, liver, spleen, and thymus were removed and weighed immediately after sacrifice. The plasma corticosterone (CORT) and vitamin D3 metabolites were measured. (3) We found elevated CORT levels in both cold water-immersed groups; however, they did not alter body and muscle weight. Body weight and muscle loss occurred in groups with exogenously administered DEX, with the exception of the soleus muscle in rats supplemented with vitamin D3. Decreased serum 25(OH)D3 concentrations in DEX-treated rats were observed, and the cold water immersion did not affect vitamin D3 levels. (4) Our results indicate that DEX-induced muscle loss was abolished in rats supplemented with vitamin D3, especially in the soleus muscle.

Vitamin D Supplementation Improves the Effects of the Rehabilitation Program on Balance and Pressure Distribution in Patients after Anterior Cervical Interbody Fusion-Randomized Control Trial.

STUDY DESIGN: A double-blinded, randomized controlled trial. BACKGROUND: Surgery is effective in reducing pain intensity in patients with cervical disc disease. However, functional measurements demonstrated that the results have been not satisfactory enough. Thus, rehabilitation programs combined with the supplementation of vitamin D could play an essential role. METHODS: The study recruited 30 patients, aged 20 to 70 years, selected for anterior cervical interbody fusion (ACIF). The patients were randomly divided into the placebo (Pl) and vitamin D (3200 IU D3/day) supplemented groups. The functional tests limits of stability (LOS), risk of falls (RFT), postural stability (PST), Romberg test, and foot pressure distribution were performed before supplementation (BS-week 0), five weeks after supplementation (AS-week 5), four weeks after surgery (BSVR-week 9), and 10 weeks after supervising rehabilitation (ASVR-week 19). RESULTS: The concentration of 25(OH)D3 in the serum, after five weeks of supplementation, was significantly increased, while the Pl group maintained the same. The RFT was significantly reduced after five weeks of vitamin D supplementation. Moreover, a further significant decrease was observed following rehabilitation. In the Pl group, no changes in the RFT were observed. The overall postural stability index (OSI), LOS, and the outcomes of the Romberg test significantly improved in both groups; however, the effects on the OSI were more pronounced in the D3 group at the end of the rehabilitation program. CONCLUSIONS: Our data suggest that vitamin D supplementation positively affected the rehabilitation program in patients implemented four weeks after ACIF by reducing the risk of falls and improving postural stability.

Vitamin D Deficiency Is Associated with Muscle Atrophy and Reduced Mitochondrial Function in Patients with Chronic Low Back Pain.

Recent studies show that vitamin D deficiency may be responsible for muscle atrophy. The purpose of this study was to investigate markers of muscle atrophy, signalling proteins, and mitochondrial capacity in patients with chronic low back pain with a focus on gender and serum vitamin D level. The study involved patients with chronic low back pain (LBP) qualified for posterior lumbar interbody fusion (PLIF). Patients were divided into three groups: supplemented (SUPL) with vitamin D (3200 IU/day for 5 weeks), placebo with normal levels of vitamin D (SUF), and the placebo group with vitamin D deficiency (DEF). The marker of muscle atrophy including atrogin-1 and protein content for IGF-1, Akt, FOXO3a, PGC-1α, and citrate synthase (CS) activity were determined in collected multifidus muscle. In the paraspinal muscle, IGF-1 levels were higher in the SUF group as compared to both the SUPL and DEF groups (p < 0.05). In the SUPL group, we found significantly increased protein content for pAkt (p < 0.05) and decreased level of FOXO3a (p < 0.05). Atrogin-1 content was significantly different between men and women (p < 0.05). The protein content of PGC-1α was significantly higher in the SUF group as compared to the DEF group (p < 0.05). CS activity in the paraspinal muscle was higher in the SUPL group than in the DEF group (p < 0.05). Our results suggest that vitamin D deficiency is associated with elevated oxidative stress, muscle atrophy, and reduced mitochondrial function in the multifidus muscle. Therefore, vitamin D-deficient LBP patients might have reduced possibilities on early and effective rehabilitation after PLIF surgery.

The Preoperative Supplementation With Vitamin D Attenuated Pain Intensity and Reduced the Level of Pro-inflammatory Markers in Patients After Posterior Lumbar Interbody Fusion.

The aim of this experimental study was to assess whether 5 weeks of preoperative supplementation with vitamin D affects the intensity of pain and the level of inflammatory markers in patients undergoing posterior lumbar interbody fusion (PLIF) followed by rehabilitation. 42 patients were divided, by double-blind randomization, into two groups: supplemented (SUPL) vitamin D (3200 IU dose of vitamin D/day for 5 weeks) and placebo group (PL) treated with vegetable oil. The 10-week program of early rehabilitation (3 times a week) was initiated 4 weeks following PLIF. Measurements of serum 25(OH)D3 and CRP, IL-6, TNF-α, and IL-10 were performed. Pain intensity was measured using VAS. After supplementation with vitamin D serum, the concentration of 25(OH)D3 significantly increased in the SUPL group (∗ p < 0.005) and was significantly higher as compared to the PL group (∗ p < 0.001). A significant reduction in pain intensity was observed 4 weeks after surgery and after rehabilitation in both groups. In the SUPL group, serum CRP and IL-6 concentration significantly decreased after rehabilitation, compared with the postsurgical level (a p < 0.04). The level of TNF-α was significantly lower after rehabilitation only in the supplemented group (∗ p < 0.02). There were no significant changes in the IL-10 level in both groups during the study. Our data indicate that supplementation with vitamin D may reduce systemic inflammation and when combined with surgery and early postsurgical rehabilitation, it may decrease the intensity of pain in LBP patients undergoing PLIF. Data indicate that LBP patients undergoing spine surgery should use vitamin D perioperatively as a supplement.

Vitamin D supplementation attenuates oxidative stress in paraspinal skeletal muscles in patients with low back pain.

PURPOSE: The aim of the study was to evaluate markers of oxidative stress and vitamin D receptor in paraspinal muscles in low back pain patients with vitamin D deficiency, with normal level of vitamin D, and after 5 weeks of vitamin D supplementation. METHODS: Patients were divided into three groups: supplemented (SUP) with vitamin D, placebo with normal concentration of vitamin D (SUF), and the placebo group with vitamin D deficiency (DEF). The concentration of serum vitamin D was measured before and after the supplementation with vitamin D (3200 IU/ day for 5 weeks). Markers of lipid and protein peroxidation, the activity of antioxidant enzymes, and protein content of vitamin D receptor was determined in multifidus muscle of patients. RESULTS: Vitamin D supplementation increased serum level of 25(OH)D3 (p < 0.001). In paraspinal muscle level of 8-isoprostanes and protein carbonyls was higher in DEF group as compared to the SUP group (p < 0.05). Antioxidant enzyme activity and vitamin D receptor in paraspinal muscle altered between the groups with different serum vitamin D concentration. The cytosolic superoxide dismutase and glutathione peroxidase activities were significantly higher in DEF group as compared to the SUP group (p < 0.05). CONCLUSIONS: An attenuation of markers of free radical damage of lipids and proteins was observed in participants supplemented with Vitamin D. Antioxidant enzyme activities in skeletal muscle differ among patients with different serum vitamin D concentration. Monitoring oxidative stress and VDR protein content might be useful for future studies on the mechanism(s) of vitamin D action in muscle.

Methyl-beta-cyclodextrin induces mitochondrial cholesterol depletion and alters the mitochondrial structure and bioenergetics.

There is growing evidence of mitochondrial membrane raft-like microdomains that are involved in the apoptotic pathway. The aim of this study was to investigate the effect of methyl-beta-cyclodextrin (MßCD), being a well-known lipid microdomain disrupting agent and cholesterol chelator, on the structure and bioenergetics of rat liver mitochondria (RLM). We observed that MßCD decreases the function of RLM, induces changes in the mitochondrial configuration state and decreases the calcium chloride-induced swelling. These data suggest that disruption of mitochondrial raft-like microdomains by cholesterol efflux on one hand impairs mitochondrial bioenergetics, but on the other hand it protects the mitochondria from swelling.