Polymorphisms in Vitamin D Receptor Genes in Association with Childhood Autism Spectrum Disorder
Both genetic and environmental factors have been implicated in the etiology of autism spectrum disorder (ASD). This case-control study aimed to determine the association of single-nucleotide polymorphisms (SNPs) rs731276 (TaqI), rs1568820 (Cdx2), rs1544410 (BsmI), and rs2228570 (FokI) in the vitamin D receptor (VDR) gene with susceptibility of childhood ASD and severity of the disease. A total of 201 children with ASD and 200 healthy controls from the Han Chinese population were recruited. SNP genotyping was carried out by TaqMan probe-based real-time PCR using genomic DNA extracted from blood cells. Among four examined SNPs, only the CT genotype (odds ratio (OR) = 1.96, 95% confidence interval (CI) = 1.05–3.68, ) and the C allele (OR = 1.88, 95% CI = 1.02–3.46, ) of the rs731276 were significantly associated with increased risks of childhood ASD. None of the SNPs were associated with severity of childhood ASD. Our results reveal that certain polymorphisms in the VDR gene are a risk factor related to childhood ASD in the Han Chinese population.
The Role of Vitamin D in Nervous System Health and Disease.
Vitamin D and its metabolites have pleomorphic roles in both nervous system health and disease. Animal models have been paramount in contributing to our knowledge and understanding of the consequences of vitamin D deficiency on brain development and its implications for adult psychiatric and neurological diseases. The conflation of in vitro, ex vivo, and animal model data provide compelling evidence that vitamin D has a crucial role in proliferation, differentiation, neurotrophism, neuroprotection, neurotransmission, and neuroplasticity. Vitamin D exerts its biological function not only by influencing cellular processes directly, but also by influencing gene expression through vitamin D response elements. This review highlights the epidemiological, neuropathological, experimental, and molecular genetic evidence implicating vitamin D as a candidate in influencing susceptibility to a number of psychiatric and neurological diseases. The strength of evidence varies for schizophrenia, autism, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease, and is especially strong for MS.
https://www.researchgate.net/publicatio ... nd_Disease
Randomized controlled trial of vitamin D supplementation in children with autism spectrum disorder
Autism spectrum disorder (ASD) is a frequent developmental disorder characterized by pervasive deficits in social interaction, impairment in verbal and nonverbal communication, and stereotyped patterns of interests and activities. It has been previously reported that there is vitamin D deficiency in autistic children; however, there is a lack of randomized controlled trials of vitamin D supplementation in ASD children.
This study is a double-blinded, randomized clinical trial (RCT) that was conducted on 109 children with ASD (85 boys and 24 girls; aged 3–10 years). The aim of this study was to assess the effects of vitamin D supplementation on the core symptoms of autism in children. ASD patients were randomized to receive vitamin D3 or placebo for 4 months. The serum levels of 25-hydroxycholecalciferol (25 (OH)D) were measured at the beginning and at the end of the study. The autism severity and social maturity of the children were assessed by the Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and the Autism Treatment Evaluation Checklist (ATEC). Trial registration number: UMIN-CTR Study Design: trial number: UMIN000020281.
Supplementation of vitamin D was well tolerated by the ASD children. The daily doses used in the therapy group was 300 IU vitamin D3/kg/day, not to exceed 5,000 IU/day. The autism symptoms of the children improved significantly, following 4-month vitamin D3 supplementation, but not in the placebo group. This study demonstrates the efficacy and tolerability of high doses of vitamin D3 in children with ASD.
This study is the first double-blinded RCT proving the efficacy of vitamin D3 in ASD patients. Depending on the parameters measured in the study, oral vitamin D supplementation may safely improve signs and symptoms of ASD and could be recommended for children with ASD. At this stage, this study is a single RCT with a small number of patients, and a great deal of additional wide-scale studies are needed to critically validate the efficacy of vitamin D in ASD.
http://onlinelibrary.wiley.com/doi/10.1 ... 2/abstract
Association between circulating 25-hydroxyvitamin D levels and psoriasis, and correlation with disease severity: a meta-analysis. Abstract
Psoriasis is a chronic, autoimmune, inflammatory skin disorder. 25-hydroxy vitamin D [25(OH)D] deficiency may contribute to the pathogenesis of psoriasis through reduction in antiproliferative, anti-inflammatory and antiangiogenic activities.
To evaluate the relationship between circulating 25(OH)D levels and psoriasis, and to determine the correlation between serum/plasma 25(OH)D levels and psoriasis severity.
We performed a meta-analysis to compare serum/plasma 25(OH)D levels between patients with psoriasis and healthy controls (HCs), and to determine the correlation coefficients between circulating 25(OH)D levels and psoriasis severity as assessed by Psoriasis Area and Severity Index (PASI).
Ten articles with a total of 571 patients with psoriasis and 496 HCs were included. The 25(OH)D level was significantly lower in the psoriasis group than in the HC group. Subgroup analysis by sample size revealed a significantly lower level of 25(OH)D in the psoriasis group for large (N > 80) but not for small (N < 80) sample sizes. Stratification by adjustment for age and/or sex or sample type revealed a significantly lower 25(OH)D level in the psoriasis group after adjustment for serum but not after nonadjustment for plasma. Meta-analysis of the correlation coefficients revealed a small but statistically significant positive correlation between circulating 25(OH)D levels and PASI.
This meta-analysis demonstrated that circulating 25(OH)D levels are lower in patients with psoriasis, and that a small but statistically significant negative correlation exists between 25(OH)D levels and psoriasis severity.
Antimicrobial implications of vitamin D
Evidence exists that vitamin D has a potential antimicrobial activity and its deficiency has deleterious effects on general well-being and longevity. Vitamin D may reduce the risk of infection through multiple mechanisms. Vitamin D boosts innate immunity by modulating production of anti-microbial peptides (AMPs) and cytokine response. Vitamin D and its analogues via these mechanisms are playing an increasing role in the management of atopic dermatitis, psoriasis, vitiligo, acne and rosacea. Vitamin D may reduce susceptibility to infection in patients with atopic dermatitis and the ability to regulate local immune and inflammatory responses offers exciting potential for understanding and treating chronic inflammatory dermatitides. Moreover, B and T cell activation as well as boosting the activity of monocytes and macrophages also contribute to a potent systemic anti-microbial effect. The direct invasion by pathogenic organisms may be minimized at sites such as the respiratory tract by enhancing clearance of invading organisms. A vitamin D replete state appears to benefit most infections, with the possible noteworthy exception of Leishmaniasis. Antibiotics remain an expensive option and misuse of these agents results in significant antibiotic resistance and contributes to escalating health care costs. Vitamin D constitutes an inexpensive prophylactic option and possibly therapeutic product either by itself or as a synergistic agent to traditional antimicrobial agents. This review outlines the specific antimicrobial properties of vitamin D in combating a wide range of organisms. We discuss the possible mechanisms by which vitamin D may have a therapeutic role in managing a variety of infections.
Vitamin D receptor Fok1 & Bsm 1 Gene Polymorphisms in Systemic Lupus Erythematosus and Osteoarthritis: Autoimmune Inflammatory versus Degenerative Model.
Vitamin D deficiency has been described in SLE and OA. Low vitamin D level is prevalent in Egyptian SLE patients while controversial studies are present regarding its level in OA patients in Egypt. We investigated whether vitamin D receptor (VDR) genes Bsm1 and Fok1 polymorphisms could be used as genetic markers for the susceptibility to SLE and /or OA in a sample of Egyptian population. The study was carried out on 100 SLE patients, 100 osteoarthritic patients and 100 normal controls using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Our results showed a statistically significant difference in Fok1 genotype distribution between SLE and OA patients (p=0.001). In SLE group, the "f" allele was significantly over-represented where 30% had "f" allele compared to 0% in OA (P = 0.03). Fok1 ff genotypes showed a significant association with disease activity in SLE patients. In addition, the fb haplotype frequency was significantly higher in SLE patients than controls (P=0.01). In conclusion Fok1 genotype and f allelic frequencies may be susceptible risk factors for SLE rather than OA in Egyptian patients.
Vitamin D supplementation attenuates the behavioral scores of neuropathic pain in rats.
Neuropathic pain due to lesion or dysfunction of the peripheral or central nervous system is often refractory to the conventional analgesics. Currently, there is no proven treatment to prevent or cure neuropathic pain. A recent surge of new data suggests the potential effects of vitamin D in the medical community. This study was designed to determine whether acute or chronic vitamin D administration was effective in alleviating symptoms of neuropathic pain in a rat model of neuropathic pain.
MATERIALS AND METHODS:
Neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve in the rats that resulted in thermal hyperalgesia, mechanical, and cold allodynia.
Acute vitamin D injections (250, 500, and 1000 unit/kg i.p.) on the 7th, 14th, and 21st postoperative days could not attenuate mechanical and cold allodynia as well as heat hyperalgesia compared to CCI group. But when vitamin D (1000 unit/kg i.p.) administration was started on the first day after surgery and given daily until the 21st day, cold allodynia and heat hyperalgesia considerably were attenuated. However, no differences in paw withdrawal thresholds were observed.
These results indicate that chronic vitamin D administrations can attenuate the behavioral scores of neuropathic pain in rats.
Does vitamin D deficiency predict early conversion of clinically isolated syndrome? A preliminary Egyptian study.
It has been suggested that vitamin D influences the immunoregulation and subsequently affects the risk for conversion of clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (MS). There is little information regarding the relationship between levels of vitamin D and CIS conversion to MS in Egyptian patients.
It is to study contribution of vitamin D deficiency to conversion of CIS to clinically definite multiple sclerosis (CDMS) and correlation of vitamin D level to cognitive and magnetic resonance imaging (MRI) results.
PATIENTS AND METHODS:
A longitudinal prospective case control study was conducted on 43 Egyptian patients diagnosed as CIS according to McDonald criteria (2010). Clinical presentation, brain MRI and 25-hydroxyvitamin D levels were evaluated at baseline and after one-year follow-up.
The CIS patients that converted to MS showed significant lower vitamin D level (p < 0.001) than the non-convertors. Multivariate logistic regression analysis revealed that the CIS patients with lower 25-hydroxyvitamin D level (p < 0.001) are at higher risk for early conversion to MS. There was a significant positive correlation between the vitamin D level and PASAT (r = 0.36, p = 0.02). It was found that there was a significant negative correlation between vitamin D level and MRI T2 load (r = -0.38, p = 0.01).
The low level of 25-hydroxyvitamin D may predict early conversion to clinically definite MS. Early vitamin D supplementation is recommended in patients with CIS.
Genomic Effects of the Vitamin D Receptor: Potentially the Link between Vitamin D, Immune Cells, and Multiple Sclerosis
Vitamin D has a plethora of functions that are important for the maintenance of general health and in particular, the functional integrity of the immune system, such as promoting an anti-inflammatory cytokine profile and reducing the Treg/Th17 ratio. Multiple sclerosis (MS) is a chronic, inflammatory, and neurodegenerative central nervous system (CNS) disorder of probable autoimmune origin. MS is characterized by recurring or progressive demyelination and degeneration of the CNS due in part to a misguided immune response to as yet undefined (CNS) antigens, potentially including myelin basic protein and proteolipid protein. MS has also been shown to be associated significantly with environmental factors such as the lack of vitamin D. The role of vitamin D in the pathogenesis and progression of MS is complex. Recent genetic studies have shown that various common MS-associated risk-single-nucleotide polymorphisms (SNPs) are located within or in the vicinity of genes associated with the complex metabolism of vitamin D. The functional aspects of these genetic associations may be explained either by a direct SNP-associated loss- or gain-of-function in a vitamin D-associated gene or due to a change in the regulation of gene expression in certain immune cell types. The development of new genetic tools using next-generation sequencing: e.g., chromatin immunoprecipitation sequencing (ChIP-seq) and the accompanying rapid progress of epigenomics has made it possible to recognize that the association between vitamin D and MS could be based on the extensive and characteristic genomic binding of the vitamin D receptor (VDR). Therefore, it is important to analyze comprehensively the spatiotemporal VDR binding patterns that have been identified using ChIP-seq in multiple immune cell types to reveal an integral profile of genomic VDR interaction. In summary, the aim of this review is to connect genomic effects vitamin D has on immune cells with MS and thus, to contribute to a better understanding of the influence of vitamin D on the etiology and the pathogenesis of this complex autoimmune disease.
https://www.frontiersin.org/articles/10 ... 00477/full
High-dose ω-3 Fatty Acid Plus Vitamin D3 Supplementation Affects Clinical Symptoms and Metabolic Status of Patients with Multiple Sclerosis: A Randomized Controlled Clinical Trial.
Background: Combined omega-3 fatty acid and vitamin D supplementation may improve multiple sclerosis (MS) by correcting metabolic abnormalities and attenuating oxidative stress and inflammation.
Objective: This study aimed to determine the effects of ω-3 fatty acid and vitamin D cosupplementation on the disability score and metabolic status of patients with MS.
Methods: This was a randomized, placebo-controlled clinical trial with Expanded Disability Status Scale (EDSS) score and inflammation as primary outcomes and oxidative stress biomarkers and metabolic profile as secondary outcomes. Patients, aged 18-55 y, were matched for disease EDSS scores, gender, medications, BMI, and age (n = 53) and randomly received a combined 2 × 1000 mg/d ω-3 fatty acid and 50,000 IU/biweekly cholecalciferol supplement or placebo for 12 wk. The placebos were matched in colour, shape, size, packaging, smell, and taste with supplements. Fasting blood samples were collected at baseline and end of intervention to measure different outcomes. Multiple linear regression models were used to assess treatment effects on outcomes adjusting for confounding variables.
Results: Patients taking ω-3 fatty acid plus vitamin D supplements showed a significant improvement in EDSS (β -0.18; 95% CI: -0.33, -0.04; P = 0.01), compared with placebo. Serum high-sensitivity C-reactive protein (β -1.70 mg/L; 95% CI: -2.49, -0.90 mg/L; P < 0.001), plasma total antioxidant capacity (β +55.4 mmol/L; 95% CI: 9.2, 101.6 mmol/L; P = 0.02), total glutathione (β +51.14 µmol/L; 95% CI: 14.42, 87.87 µmol/L; P = 0.007), and malondialdehyde concentrations (β -0.86 µmol/L; 95% CI: -1.10, -0.63 µmol/L; P < 0.001) were significantly improved in the supplemented group compared with the placebo group. In addition, ω-3 fatty acid and vitamin D cosupplementation resulted in a significant reduction in serum insulin, insulin resistance, and total/HDL-cholesterol, and a significant increase in insulin sensitivity and serum HDL-cholesterol concentrations.
Conclusion: Overall, taking ω-3 fatty acid and vitamin D supplements for 12 wk by patients with MS had beneficial effects on EDSS and metabolic status. This trial was registered at the Iranian website (www.irct.ir) for registration of clinical trials as IRCT2017090133941N20.
Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial
free full text https://jamanetwork.com/journals/jama/f ... cle/185854
Context Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures; however, adherence to daily supplementation is typically poor.
Objective To determine whether a single annual dose of 500 000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture.
Design, Setting, and Participants A double-blind, placebo-controlled trial of 2256 community-dwelling women, aged 70 years or older, considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were randomly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years. The study concluded in 2008.
Intervention 500 000 IU of cholecalciferol or placebo.
Main Outcome Measures Falls and fractures were ascertained using monthly calendars; details were confirmed by telephone interview. Fractures were radiologically confirmed. In a substudy, 137 randomly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels.
In the substudy, the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3% of the substudy participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group, 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L, were approximately 90 nmol/L at 3 months, and remained higher than the placebo group 12 months after dosing.
Conclusion Among older community-dwelling women, annual oral administration of high-dose cholecalciferol resulted in an increased risk of falls and fractures.
ha a chuckle from the intro:
"The rationale for this dose was based on data that an oral dose of 500 000 IU (administered as 50 000 IU daily for 10 days) produced a mean (SD) increase in 25-hydroxycholecalciferol of 32 (15) nmol/L at 17 (7) weeks after dose"
that's what i do if and as needed (3 times in my entire life so far) - never omitting appropriate cofactors (mentioned zero times in the article's full text) - and knowing that when properly nourished, my own levels can jump by 170 nmol/l after only 8 days x 50K.
the other handy protocol involves ensuring adequate seasonal outdoor time under that flaming ball of gas in the sky.
pursue optimal self care at least as actively as a diagnosis
ask for referrals to preventive health care specialists eg dietitians
don't let suboptimal self care muddy any underlying diagnostic picture!
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