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.

(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.

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.

Klotho is a beta-glucuronidase that reveals both anti-inflammatory and anti-oxidative properties that have been associated with mechanisms of aging. The study aimed to analyze the relationships between the serum concentration of soluble α-Klotho and cellular activity of two populations of lymphocytes; T and NKT-like cells corresponding to the level of cytokine secretion; i.e., IFN-γ, TNF-α, and IL-6. The studied population comprised three age groups: young individuals (‘young’), seniors aged under 85 (‘old’), and seniors aged over 85 (‘oldest’). Both NKT-like and T cells were either non-cultured or cultured for 48 h and stimulated appropriately with IL-2, LPS or PMA with ionomycin to compare with unstimulated control cells. In all studied age groups non-cultured or cultured NKT-like cells revealed higher expressions of TNF-α, IL-6, and IFN-γ than T cells. α-Klotho concentration in serum decreased significantly in the process of aging. Intriguingly, only IFN-γ expression revealed a positive correlation with α-Klotho protein serum concentration in both non-cultured and cultured T and NKT-like cells. Since IFN-γ is engaged in the maintenance of immune homeostasis, the observed relationships may indicate the involvement of α-Klotho and cellular IFN-γ expression in the network of adaptive mechanisms developed during the process of human aging.