cholecalciferol and Amyotrophic-Lateral-Sclerosis

To investigate the effects of cholecalciferol supplementation on the progression of motor disability in a cohort of amyotrophic lateral sclerosis (ALS) patients with low blood 25-hydroxyvitamin D3 [25(OH)D] levels, on the basis of the hypothesis of potential neuroprotective effects of vitamin D supplementation.. Forty-eight ALS patients, 34 with deficient (<20 ng/mL) and 14 with insufficient (20-29 ng/mL) serum levels of 25(OH)D, were randomized and treated by 3 different doses of cholecalciferol [50.000, 75.000 and 100.000 international units (IU) /month] and evaluated after 6-months. Assessment of motor dysfunction at baseline and after 6 months included ALS Functional Rating Scale-Revised (ALFRS-R) and upper motor neuron (UMN) scores and blood samples for 25(OH)D levels.. Clinical data of 33 patients were available after 6 months. Analysis of Covariance (ANCOVA), with pre-treatment measurements included as covariate, did not show statistically significant differences in the ALSFRS-R (p > 0.05) and UMN (p > 0.05) among the patient groups who underwent 3 different doses of cholecalciferol. Conversely, the treatment with 75.000 IU/month or 100.000 IU/month induced a significant increase in serum levels of 25(OH)D in comparison with the supplementation with 50.000 IU/month; no significant differences were found between 75.000 IU/month and 100.000 IU/month.. Our findings highlighted that 6-month supplementation of vitamin D in ALS patients had no significant effects on motor dysfunction. However, it is recommended to prevent medical complications of vitamin D deficiency in ALS patients as well as in other populations of neurodegenerative patients, characterized by low mobility and decreased sun exposure.

Topics: Amyotrophic Lateral Sclerosis; Cholecalciferol; Dietary Supplements; Disabled Persons; Humans; Motor Disorders; Vitamin D; Vitamin D Deficiency

Dietary vitamin D3 (D3) restriction reduces paw grip endurance and motor performance in G93A mice, and increases inflammation and apoptosis in the quadríceps of females. ALS, a neuromuscular disease, causes progressive degeneration of motor neurons in the brain and spinal cord.. We analyzed the spinal cords of G93A mice following dietary D3 restriction at 2.5% the adequate intake (AI) for oxidative damage (4-HNE, 3-NY), antioxidant enzymes (SOD2, catalase, GPx1), inflammation (TNF-α, IL-6, IL-10), apoptosis (bax/bcl-2 ratio, cleaved/pro-caspase 3 ratio), neurotrophic factor (GDNF) and neuron count (ChAT, SMI-36/SMI-32 ratio).. Beginning at age 25 d, 42 G93A mice were provided food ad libitum with either adequate (AI;1 IU D3/g feed; 12 M, 11 F) or deficient (DEF; 0.025 IU D3/g feed; 10 M, 9 F) D3. At age 113 d, the spinal cords were analyzed for protein content. Differences were considered significant at P ≤ 0.10, since this was a pilot study.. DEF mice had 16% higher 4-HNE (P = 0.056), 12% higher GPx1 (P = 0.057) and 23% higher Bax/Bcl2 ratio (P = 0.076) vs. AI. DEF females had 29% higher GPx1 (P = 0.001) and 22% higher IL-6 (P = 0.077) vs. AI females. DEF males had 23% higher 4-HNE (P = 0.066) and 18% lower SOD2 (P = 0.034) vs. AI males. DEF males had 27% lower SOD2 (P = 0.004), 17% lower GPx1 (P = 0.070), 29% lower IL-6 (P = 0.023) and 22% lower ChAT (P = 0.082) vs. DEF females.. D3 deficiency exacerbates disease pathophysiology in the spinal cord of G93A mice, the exact mechanisms are sex-specific. This is in accord with our previous results in the quadriceps, as well as functional and disease outcomes.

Topics: Amyotrophic Lateral Sclerosis; Animals; Cholecalciferol; Female; Male; Mice; Mice, Transgenic; Nerve Tissue Proteins; Spinal Cord

We previously demonstrated that dietary vitamin D(3) at 10x the adequate intake (AI) attenuates the decline in functional capacity in the G93A mouse model of ALS. We hypothesized that higher doses would elicit more robust changes in functional and disease outcomes.. To determine the effects of dietary vitamin D(3) at 50xAI on functional outcomes (motor performance, paw grip endurance) and disease severity (clinical score), as well as disease onset, disease progression and lifespan in the transgenic G93A mouse model of ALS.. Starting at age 25 d, 100 G93A mice (55 M, 45 F) were provided ad libitum with either an adequate (AI; 1 IU D(3)/g feed) or high (HiD; 50 IU D(3)/g feed) vitamin D(3) diet.. HiD females consumed 9% less food corrected for body weight vs. AI females (P = 0.010). HiD mice had a 12% greater paw grip endurance over time between age 60-141 d (P = 0.015), and a 37% greater score during disease progression (P = 0.042) vs. AI mice. Although HiD females had a non-significant 31% greater CS prior to disease onset vs. AI females, they exhibited a significant 20% greater paw grip endurance AUC (P = 0.020) when corrected for clinical score.. Dietary D(3) supplementation at 50x the adequate intake attenuated the decline in paw grip endurance, but did not influence age at disease onset, hindlimb paralysis or endpoint in the transgenic G93A mouse model of ALS. Furthermore, females may have reached the threshold for vitamin D(3) toxicity as evidence by reduced food intake and greater disease severity prior to disease onset.

Topics: Amyotrophic Lateral Sclerosis; Animals; Body Weight; Cholecalciferol; Dietary Supplements; Disease Models, Animal; Disease Progression; Eating; Female; Hand Strength; Hindlimb; Male; Mice; Mice, Transgenic; Physical Endurance; Psychomotor Performance

Vitamin D has antioxidant, anti-inflammatory, and neuroprotective properties, and may mitigate amyotrophic lateral sclerosis (ALS) pathology.. To determine the effects of dietary vitamin D(3) (D(3)) at 10-fold the adequate intake (AI) on functional and disease outcomes and lifespan in the transgenic G93A mouse model of ALS.. Starting at age 40 days, 32 G93A mice (21 M, 11 F) were provided ad libitum with either an adequate (AI; 1 IU/g feed) or high (HiD; 10 IU/g feed) D(3) diet. Differences were considered significant at P≤ 0.10, as this was a pilot study.. For paw grip endurance, HiD mice had a 7% greater score between 60-133 d versus AI mice (P= 0.074). For motor performance, HiD mice had a 22% greater score between 60-133 days (P= 0.074) versus AI mice due to changes observed in male mice, where HiD males had a 33% greater score (P= 0.064) versus AI males. There were no significant diet differences in disease onset, disease progression, or lifespan.. Although disease outcomes were not affected, D(3) supplementation at 10-fold the AI improved paw grip endurance and motor performance in the transgenic G93A mouse model of ALS, specifically in males.

Topics: Amyotrophic Lateral Sclerosis; Animals; Cholecalciferol; Dietary Supplements; Disease Models, Animal; Female; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Pilot Projects; Recovery of Function; Sex Factors; Superoxide Dismutase; Up-Regulation

Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease characterized by motor neuron death in the central nervous system. Vitamin D supplementation increases antioxidant activity, reduces inflammation and improves motor neuron survival. We have previously demonstrated that vitamin D(3) supplementation at 10× the adequate intake improves functional outcomes in a mouse model of ALS.. To determine whether vitamin D deficiency influences functional and disease outcomes in a mouse model of ALS.. At age 25 d, 102 G93A mice (56 M, 46 F) were divided into two vitamin D(3) groups: 1) adequate (AI; 1 IU D(3)/g feed) and 2) deficient (DEF; 0.025 IU D(3)/g feed). At age 113 d, tibialis anterior (TA), quadriceps (quads) and brain were harvested from 42 mice (22 M and 20 F), whereas the remaining 60 mice (34 M and 26 F) were followed to endpoint.. During disease progression, DEF mice had 25% (P=0.022) lower paw grip endurance AUC and 19% (P=0.017) lower motor performance AUC vs. AI mice. Prior to disease onset (CS 2), DEF mice had 36% (P=0.016) lower clinical score (CS) vs. AI mice. DEF mice reached CS 2 six days later vs. AI mice (P=0.004), confirmed by a logrank test which revealed that DEF mice reached CS 2 at a 43% slower rate vs. AI mice (HR= .57; 95% CI: 0.38, 1.74; P=0.002). Body weight-adjusted TA (AI: r=0.662, P=0.001; DEF: r=0.622, P=0.006) and quads (AI: r=0.661, P=0.001; DEF: r=0.768; P<0.001) weights were strongly correlated with age at CS 2.. Vitamin D(3) deficiency improves early disease severity and delays disease onset, but reduces performance in functional outcomes following disease onset, in the high-copy G93A mouse.

Topics: Amyotrophic Lateral Sclerosis; Animals; Cholecalciferol; Disease Models, Animal; Male; Mice; Polymerase Chain Reaction; Treatment Outcome; Vitamin D Deficiency