BACKGROUND & OBJECTIVE:Western studies show that up to 65 per cent of patients with Crohn's disease have low serum 25-hydroxy vitamin D concentrations, and 45 per cent of these patients have metabolic bone disease. No data are available from India or from any country with comparable climatic conditions or ethnicity. We carried out this study to measure the serum 25 (OH) vitamin D levels of Crohn's disease patients and compare with matched controls and to assess the consequences of low 25 (OH) vitamin D levels on bone and mineral metabolism in these patients.

METHODS:Adult patients with Crohn's disease were compared with age and sex matched patients diagnosed to have irritable bowel syndrome. Serum 25 (OH) vitamin D, the effect of disease characteristics, sunlight exposure and milk consumption on 25 (OH) vitamin D level, and the consequences of low 25 (OH) vitamin D level on bone and mineral metabolism were assessed.

RESULTS:Thirty four patients with Crohn's disease (M:F, 24:10, age 39.2 +/- 12.9 yr) and 34 controls (M:F, 24:10, age 38.9 +/- 13.4 yr) were studied. 25 (OH) vitamin D levels were significantly lower in patients with Crohn's disease as compared to controls (Crohn's disease vs controls: 16.3 +/- 10.8 vs 22.8 +/- 11.9 ng/ml; P<0.05). The severity of disease activity as assessed by the Harvey Bradshaw score correlated negatively (Correlation coefficient -0.484, significance P<0.004), and the duration of sunlight exposure correlated positively (Correlation coefficient 0.327, significance P=0.007) with the serum 25 (OH) vitamin D level.

INTERPRETATION & CONCLUSION:Serum 25 (OH) vitamin D levels were significantly lower among patients with Crohn's disease as compared to age and sex matched controls. Further, 25 (OH) vitamin D levels in patients with Crohn's disease were lower in those with severe disease activity and less sun exposure. Further studies need to be done to correlate low 25 (OH) vitamin D level with bone density and assess the effect of vitamin D supplementation in these patients.

BACKGROUND: QR-333, a topical compound that contains quercetin, a flavonoid with aldose reductase inhibitor effects, ascorbyl palmitate, and vitamin D(3), was formulated to decrease the oxidative stress that contributes to peripheral diabetic neuropathy and thus alleviate its symptoms. This proof-of-principle study assessed the efficacy and safety of QR-333 against placebo in a small cohort of patients with diabetic neuropathy. METHODS: This randomized, placebo-controlled, double-blind trial included 34 men and women (21-71 years of age) with Type 1 or 2 diabetes and diabetic neuropathy who applied QR-333 or placebo (2:1 ratio), three times daily for 4 weeks, to each foot where symptoms were experienced. Five-point scales were used to determine changes from baseline to endpoint in symptoms and quality of life (efficacy). Safety was assessed through concomitant medications, adverse events, laboratory evaluations, and physical examinations. RESULTS: QR-333 reduced the severity of numbness, jolting pain, and irritation from baseline values. Improvements were also seen in overall and specific quality-of-life measures. QR-333 was well tolerated. Eleven patients in the QR-333 group reported 23 adverse events (all mild or moderate); 4 in the placebo group reported 5 events (all moderate). One patient who applied QR-333 noted a pricking sensation twice, the only adverse event considered possibly related to study treatment. CONCLUSIONS: From this preliminary safety study, it appears that QR-333 may safely offer relief of symptoms of diabetic neuropathy and improve quality of life. These findings warrant further investigation of this topical compound.

PURPOSE OF REVIEW:Aromatase inhibitor-induced arthralgia (AIA) is a very common syndrome which significantly affects breast cancer survivors' quality of life, and it often leads to non-compliance with aromatase inhibitor (AI) therapy. However, the treatment of AIA remains a clinical challenge. Here, we will review the current data for acupuncture and vitamin D in the management of AIA.

RECENT FINDINGS:Acupuncture has been shown to improve AIA symptoms, but it has not consistently been proven to offer significantly more clinical benefit than sham acupuncture. Similarly, while some vitamin D trials have shown benefit, the studies have not consistently shown improvement in AIA symptoms. Neither acupuncture nor vitamin D can be touted as standard treatments for AIA. However, many patients do experience subjective improvement of their symptoms with these therapies. When other treatments, such as exercise and duloxetine, are not feasible or not effective, it is reasonable to offer a trial of acupuncture or vitamin D to patients who are suffering from AIA, as the potential harms are very few, and they do offer possible relief from AIA symptoms.

A high incidence of fractures, particularly of the hip, represents an important problem in patients with Parkinson's disease (PD), who are prone to falls and have osteoporosis. We previously showed that 25-hydroxyvitamin D (25-OHD) deficiency due to sunlight deprivation with compensatory hyperparathyroidism causes reduced bone mineral density (BMD) in elderly patients with PD. The present study was undertaken to address the possibility that sunlight exposure may maintain BMD and reduce the incidence of hip fracture in elderly patients with PD. In a prospective study, PD patients were assigned to regular sunlight exposure (n=162) or usual lifestyle (n=162), and followed for 2 years. BMD of the second metacarpal bone was measured using a computed X-ray densitometer. Incidence of hip fracture in the two patient groups during the 2 year follow-up period was assessed. At baseline, patients of both groups showed vitamin D deficiency due to sunlight deprivation with compensatory hyperparathyroidism. The exposed group patients were exposed to sunlight (3231 min/year). BMD increased by 3.8% in the sunlight-exposed group and decreased by 2.6% in the usual lifestyle group (p<.0001). Serum 25-OHD level increased from 27 nmol/L to 52 nmol/L in the sunlight-exposed group. Eleven patients sustained hip fracture in the normal lifestyle group, and 3 fractures occurred among the sunlight-exposed group (p=.03; odds ratio=2.4). Sunlight exposure can increase the BMD of vitamin D deficient bone by increasing 25-OHD concentration and leads to the prevention of hip fracture.

Cancer has surpassed heart disease as the leading cause of death in the United States. The mortality rate for cancer is high (roughly 42%), and it increases dramatically with increasing age, especially in patients between the ages of 40 and 60 years old. Currently, the efforts at cancer prevention have been minimal. The drugs developed so far are expensive and have serious side effects. There are at least 18 vitamin D-sensitive cancers. Ultraviolet light, and specifically ultraviolet B (UVB), could reduce cancer by the limited exposure of suitable skin areas to UVB of an intensity and duration insufficient to produce skin cancer. An irrational fear of skin cancer is preventing this idea from being implemented. Though skin cancer incidence is significant, mortality from skin cancer is relatively rare. Roughly 1,000,000 Americans will be affected by skin cancer but only 10,000 deaths are expected in 2005 (a 1% mortality rate). Skin cancer is easily detected and often cured by excisional biopsy alone. Current practice among practicing clinicians is to use a prescription drug substitute for UV light, calcitriol (1-25 dihydroxycholcalciferol). However, high levels of (calcitriol) are dangerous, and there is no consensus on just what a high dose or a safe dose is. Apart from skin cancer, UV light exposure possesses few risks. Additionally, a number of botanical agents such as ginkgo biloba, vitamins E and C, carotenoids, selenium and proanthocyanidins can prevent the risk of skin cancer. Ginkgo biloba also possess the following additional cancer chemopreventive qualities: (1) promoting apoptosis of cancer cells; (2) an anti-clastogenic effect on chromosomes by repairing and reconstituting broken and damaged chromosomes; (3) a powerful therapeutic effect on the treatment of fibrosis-related cancer; (4) a therapeutic effect on free radical-induced cancer; (5) a therapeutic effect on the treatment of cancer incident to the result of numerous carcinogens; (6) a therapeutic effect on preventing free radical-induced cancer; (7) an enhancing effect on radiation therapy in the treatment of cancer; and (8) a therapeutic effect on reducing the size of cancer tumors. Ginkgo biloba is widely-used and has few adverse effects. The proposed preventive treatment for cancer consists of short intermittent exposure of the least sensitive areas of the body to sunlight and/or artificial ultraviolet light. The routine testing of plasma vitamin D levels help monitor the effectiveness of the treatment and periodic checkups with a dermatologist help monitor the safety.

Background/Objectives:The goal of this work is to estimate the reduction in mortality rates for six geopolitical regions of the world under the assumption that serum 25-hydroxyvitamin D (25(OH)D) levels increase from 54 to 110 nmol/l.Subjects/Methods:This study is based on interpretation of the journal literature relating to the effects of solar ultraviolet-B (UVB) and vitamin D in reducing the risk of disease and estimates of the serum 25(OH)D level-disease risk relations for cancer, cardiovascular disease (CVD) and respiratory infections. The vitamin D-sensitive diseases that account for more than half of global mortality rates are CVD, cancer, respiratory infections, respiratory diseases, tuberculosis and diabetes mellitus. Additional vitamin D-sensitive diseases and conditions that account for 2 to 3% of global mortality rates are Alzheimer's disease, falls, meningitis, Parkinson's disease, maternal sepsis, maternal hypertension (pre-eclampsia) and multiple sclerosis. Increasing serum 25(OH)D levels from 54 to 110 nmol/l would reduce the vitamin D-sensitive disease mortality rate by an estimated 20%.Results:The reduction in all-cause mortality rates range from 7.6% for African females to 17.3% for European females. Reductions for males average 0.6% lower than for females. The estimated increase in life expectancy is 2 years for all six regions.Conclusions:Increasing serum 25(OH)D levels is the most cost-effective way to reduce global mortality rates, as the cost of vitamin D is very low and there are few adverse effects from oral intake and/or frequent moderate UVB irradiance with sufficient body surface area exposed.European Journal of Clinical Nutrition advance online publication, 6 July2011; doi:10.1038/ejcn.2011.68.

Atherosclerosis is a progressive and multifactorial disease which occurs under the influence of various risk factors including endothelial dysfunction (ED), oxidative stress, and low-density lipoprotein (LDL) oxidation. In contract to the initial hypotheses on the usefulness of vitamin E supplementation for cardiovascular disease prevention, large outcome trials showed consumption of vitamin E has no obvious effect on cardiovascular disease and, in some cases, it may even increase the rate of mortality. This seemingly unexpected finding may be due to the opposite effects of vitamin E compounds. Vitamin E is a group of compounds which have different and even opposing effects, yet in most of the studies, the exact consumed component of vitamin E is not determined. It appears that the combined consumption of gamma-tocopherol, vitamin C, vitamin D, and tetrahydrobiopterin (BH4) may be extremely effective in both preventing atherogenesis and suppressing plaque development. In this regard, one of main issues is effect of vitamin E and D deficiency on microRNAs network in atherosclerosis. Various studies have indicated that miRNAs have key roles in atherosclerosis pathogenesis. The deficiency of vitamin E and D could provide a deregulation for miRNAs network and these events could lead to progression of atherosclerosis. Here, we highlighted a variety of mechanisms involve in the progression of atherosclerosis and effects of vitamin D and E on these mechanisms. Moreover, we summarized miRNAs involve in atherosclerosis and their regulation by vitamin E and D deficiency. This article is protected by copyright. All rights reserved.

Objectives:The present study aimed to investigate the anti-inflammatory effects of vitamin D and resistance training in men with type 2 diabetes mellitus and vitamin D deficiency.

Design:This study was a randomized, placebo-controlled, double-blinded clinical trial.: IRCT20190204042621N1.

Participants:Forty-eight patients with type 2 diabetes aged 40-65 (from a total of 52 volunteers in Ardabil diabetes clinic) were randomly assigned to either the vitamin D supplementation with resistance training group (VD + RT: = 12), the resistance training group (RT: = 12), the vitamin D supplementation group (VD: = 12), or the control group (CON: = 12).

Intervention:The subjects in VD group took vitamin D supplements at 50000 IU per 2 weeks for 3 months; the subjects in RT group exercised 3 times per week for 12 weeks; and the subjects in VD + RT group participated in both treatments. Subjects in CON group were asked to maintain normal daily life pattern for the duration of the study.

Measurements:Serum Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α) and C-reactive protein (CRP) levels were determined at pre and post-test and the data were compared among the four groups and between two tests (4 × 2) using two-way ANOVA with repeated measures.

Results:IL-6 decreased significantly ( = 0.001) in all groups (VD + RT = % -71.73, RT = % -65.85, VD = % -61.70). TNF-α decreased significantly ( = 0.001) in VD + RT (% -44.90) and RT (% -40) groups. CRP showed no significant change in any group ( > 0.05).

Conclusion:Results demonstrated that vitamin D supplementation in addition to resistance training had positive effects on some inflammatory markers in T2D and vitamin D deficient men. Vitamin D supplementation was especially effective when it was complemented with exercise training.

Cancers have been the leading cause of death worldwide and poor diet and physical inactivity are major risk factors in cancer-related deaths. Micronutrients such as vitamins and minerals appear to have preventive properties against cancer. One important mechanism by which dietary changes can exert preventive effects on cancer is via modulation of micronutrient concentrations in target tissues. Many of these micronutrients are available in the form of dietary supplements, and the intake of these supplements is prevalent in various parts of the world. However in most cases it is not known which micronutrient (or combination of micronutrients) is best when it comes to lowering the risk of cancer. The present review illustrates the effect of vitamin D and ascorbic acid intake on preventing cancer.

CASE REPORT: A 29-year-old wheelchair-bound woman was presented to us by the gastroenterologist with suspected osteomalacia. She had lived in the Netherlands all her life and was born of Moroccan parents. Her medical history revealed iron deficiency, growth retardation, and celiac disease, for which she was put on a gluten-free diet. She had progressive bone pain since 2 years, difficulty with walking, and about 15 kg weight loss. She had a short stature, scoliosis, and pronounced kyphosis of the spine and poor condition of her teeth. Laboratory results showed hypocalcemia, an immeasurable serum 25-hydroxyvitamin D level, and elevated parathyroid hormone and alkaline phosphatase levels. Spinal radiographs showed unsharp, low contrast vertebrae. Bone mineral density measurement at the lumbar spine and hip showed a T-score of -6.0 and -6.5, respectively. A bone scintigraphy showed multiple hotspots in ribs, sternum, mandible, and long bones. A duodenal biopsy revealed villous atrophy (Marsh 3C) and positive antibodies against endomysium, transglutaminase, and gliadin, compatible with active celiac disease. A bone biopsy showed severe osteomalacia but normal bone volume. She was treated with calcium intravenously and later orally. Furthermore, she was treated with high oral doses of vitamin D and a gluten-free diet. After a few weeks of treatment, her bone pain decreased, and her muscle strength improved.

DISCUSSION: In this article, the pathophysiology and occurrence of osteomalacia as a complication of celiac disease are discussed. Low bone mineral density can point to osteomalacia as well as osteoporosis.

Objective:Vitamin D and C levels have inverse relation with the metabolic syndrome components and they are used as antioxidant supplements during enduring metabolic activities. In the present study, we hypothesized that the intake of vitamin D and/or C with endurance physical activity might reduce the risk of metabolic syndrome.

Methods:A randomized control study recruited 180 participants of both genders, aged between 30 and 50 years. The participants were assigned into six groups receiving different doses of vitamin D or vitamin C with or without physical activities. Data were collected over a period of 3 months, and the results were analyzed using SPSS version 20.

Results:Variations in the effect of the supplements on various body variables including: Fasting plasma glucose, total cholesterol, low-density lipoprotein cholesterol and blood pressure, showed that vitamin D has more influence compared to vitamin C. However, vitamin D and C supplements do not have any effect on weight when consumers are undergoing endurance physical exercise. But vitamin C consumer group has more effect in waist circumference, triglyceride, and high-density lipoprotein, as compared to vitamin D consumer group.

Conclusion:We conclude that, consumption of vitamin D or vitamin C supplements may improves the life of metabolic syndrome patients. However, the combination of physical activities and vitamin supplements maximize the effect, and this combination should be recommended.WHO-ICTRP IRCT20161110030823N2. Registered 01 February 2018. https://apps.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20161110030823N2.

INTRODUCTION:Maternal vitamin D deficiency is widespread health problem which is more important in pregnant women which affects fetus growth and bone development. The aim of this study was to evaluate the effect of sun exposure versus vitamin D supplementation for pregnant women with vitamin D deficiency.

MATERIALS AND METHODS:This prospective clinical trial was performed on 87 pregnant women with vitamin D deficiency. Group A was treated with vitamin D 4000 IU per day for 10 weeks, while group B was recommended for sun exposure for 30 minutes daily (30% body surface area) for 10 weeks in summer and between 10 am-4 pm in direct sunlight. After the delivery, 25-hydroxyvitamin D3 levels were measured in the same previous center. Moreover, weight, height and head circumference of fetus were measured at delivery in both groups and compared with each other.

RESULTS:After 10-week intervention, 25-hydroxyvitamin D3 levels was significantly higher in group treated with vitamin D as compared to sun expose group (31.27 versus 19.79 ng/ml). (p<0.001). However, height (p = 0.118), weight (p = 0.245) and head circumference (p = 0.681) of infants in both groups did not show significant differences.

CONCLUSION:Vitamin D supplementation is more effective than sun exposure in increasing 25-hydroxyvitamin D3 in pregnant women with vitamin D deficiency.

The treatment of alopecia is limited by a lack of therapies that induce and sustain disease remission. Given the negative psychosocial impact of hair loss, patients that do not see significant hair restoration with conventional therapies often turn to complementary and alternative medicine (CAM). Although there are a variety of CAM treatment options on the market for alopecia, only a few are backed by multiple randomized controlled trials. Further, these modalities are not regulated by the Food and Drug Administration and there is a lack of standardization of bioactive in gredients in over-the-counter vitamins, herbs, and supplements. In this article, we provide a comprehensive review of the efficacy, safety, and tolerability of CAM, including natural products and mind and body practices, in the treatment of hair loss. Overall, there is a need for additional studies investigating CAM for alopecia with more robust clinical design and standardized, quantitative outcomes.

OBJECTIVES:To explore the interrelationship and mediating effect of factors that are beneficial (i.e., antioxidants) and harmful (i.e., inflammation and oxidative stress) to the relationship between sleep and cardiometabolic health.

DESIGN:Cross-sectional data from the 2005-2006 National Health and Nutrition Examination Survey.

SETTING:Nationally representative population sample from the US.

PARTICIPANTS:Age≥ 20 y with sleep data; final analytical sample of N = 2,079.

INTERVENTIONS:N/A.

MEASUREMENTS AND RESULTS:Metabolic syndrome was classified according to the Joint Interim Statement, and sleep duration was categorized as very short, short, adequate, and long sleepers (≤4, 5-6, 7-8, and ≥9 h per night, respectively). The indirect mediation effect was quantified as large (≥ 0.25), moderate (≥ 0.09), modest (≥ 0.01), and weak (<0.01). In general, inflammation was above the current clinical reference range across all sleep duration categories, whereas oxidative stress was elevated among short and very short sleepers. Select sleep duration-cardiometabolic health relationships were mediated by C-reactive protein (CRP),γ-glutamyl transferase (GGT), carotenoids, uric acid, and vitamins C and D, and were moderated by sex. Specifically, moderate-to-large indirect mediation by GGT, carotenoids, uric acid, and vitamin D were found for sleep duration-waist circumference and systolic blood pressure relationships, whereas vitamin C was a moderate mediator of the sleep duration-diastolic blood pressure relationship.

CONCLUSIONS:Several factors related to inflammation, oxidative stress, and antioxidant status were found to lie on the casual pathway of the sleep duration-cardiometabolic health relationship. Further longitudinal studies are needed to confirm our results.

Phytochemicals and micronutrients represent a growing theme in antimicrobial defense; however, little is known about their anti-borreliae effects of reciprocal cooperation with antibiotics. A better understanding of this aspect could advance our knowledge and help improve the efficacy of current approaches towards Borrelia sp. In this study, phytochemicals and micronutrients such as baicalein, luteolin, 10-HAD, iodine, rosmarinic acid, and monolaurin, as well as, vitamins D3 and C were tested in a combinations with doxycycline for their in vitro effectiveness against vegetative (spirochetes) and latent (rounded bodies, biofilm) forms of Borrelia burgdorferi and Borrelia garinii. Anti-borreliae effects were evaluated according to checkerboard assays and supported by statistical analysis. The results showed that combination of doxycycline with flavones such as baicalein and luteolin exhibited additive effects against all morphological forms of studied Borrelia sp. Doxycycline combined with iodine demonstrated additive effects against spirochetes and biofilm, whereas with fatty acids such as monolaurin and 10-HAD it produced FICIs of indifference. Additive anti-spirochetal effects were also observed when doxycycline was used with rosmarinic acid and both vitamins D3 and C. Antagonism was not observed in any of the cases. This data revealed the intrinsic anti-borreliae activity of doxycycline with tested phytochemicals and micronutrients indicating that their addition may enhance efficacy of this antibiotic in combating Borrelia sp. Especially the addition of flavones balcalein and luteolin to a doxycycline regimen could be explored further in defining more effective treatments against these bacteria.

Epidemiology of bronchial asthma (BA) indicates a marked paradox: rapid rise in the prevalence.Simultaneous decline in mortality is mostly related to improvement in the diagnosis and therapy. In many economically developed countries the BA affects more than 10 per cent of the population, while mortality related to this respiratory disorder is below 1/100,000. Factors favorably influencing mortality of BA include new more effective medications, decline in smoking and also improved nutrition, based on awareness of protective role of vitamins. Vitamin D deficiency has a number of biological effects that are potentially instrumental in the pathogenesis and severity of BA. Increased number of randomized, controlled, interventional studies is showing positive effects of vitamin D supplementation in pediatric and in adult BA. Oxidative stress is potentially an important pathogenic factor in the progression of BA. Vitamin C (ascorbic acid) belongs to the most effective nutritional antioxidants. By counteracting oxidants, reducing generation of reactive oxygen species, vitamin C may inhibit external attacks in the respiratory tract, thus modulating the development of BA (Fig. 2, Ref. 15).

In addition to its well-known effects on bone metabolism, vitamin D is an immunomodulating hormone. Serum vitamin D levels in males 18-25 years were measured at baseline, and HPV antibody titers were measured one month following the third quadrivalent HPV vaccine dose. Vitamin D levels were>30 ng/ml (normal) in 60 males and<30 ng/ml (low) in 113 males. Reverse cumulative distribution curves and scatter plots showed higher antibody titers with low vitamin D for all vaccine strains (P<0.05). In linear regression analyses, antibody titers for all HPV strains were significantly higher among those with lower vitamin D levels and among younger participants (P<0.05). These relationships add to the body of knowledge of the complex role of vitamin D in immunoregulation.

Objectives To assess the prevalence of hypovitaminosis D, altered arterial blood pressure, and serum levels of glucose and lipids in community-dwelling women in the city of Ribeirão Preto, in the southeast of Brazil. Methods This was a cross-sectional study of women aged 40-70 years old. Calcium intake and level of sun exposure were assessed by means of a questionnaire. A blood sample was used to determine glucose, lipid profile and 25-hydroxyvitamin D (25[OH]D) concentration. Results Ninety-one women were enrolled (age = 54.2 ± 7.1 years). The mean serum 25(OH)D concentration was 25.7 ± 8.9 ng/mL. A total of 24 (26.4%) women had 25(OH)D levels < 20 ng/mL. Seventy women (76.9%) had 25(OH)D levels < 30 ng/mL. Seventy-five women (90.4%) had inadequate calcium intake, and 61 women (67%) had appropriate sun exposure, 49 of whom (80.3%) had serum 25(OH)D levels < 30 ng/mL. Conclusion This study indicates that even in community-dwelling women, living in a city with high sun exposure, serum levels of 25(OH)D > 30 ng/ml are hardly reached. Thus, it is probable that other intrinsic factors besides sun exposure may regulate the levels of vitamin D.