Unlocking the potential-vitamin D in prostate cancer prevention

Prostate cancer poses a significant health challenge globally,demanding proactive prevention strategies.This editorial explores the emerging role of vitamin D in prostate cancer prevention.While traditionally associated with bone health,vitamin D is increasingly recognized for its broader impact on immune function,cellular signaling,and cancer prevention.Epidemiological studies suggest an intriguing link between vitamin D deficiency and elevated prostate cancer risk,particularly in regions with limited sunlight exposure.Mechanistically,vitamin D regulates cellular processes,inhibiting unchecked cancer cell growth and bols-tering immune surveillance.Personalized prevention strategies,considering individual factors,are deemed essential for harnessing the full potential of vitamin D.To unlock this potential,the future calls for robust research,public awareness campaigns,dietary improvements,and vigilant medical guidance.Collaborative efforts are poised to pave the way toward a future where vitamin D stands as a sentinel in prostate cancer prevention,ushering in hope and improved health for men worldwide.

Mitigating diabetes-related complications:Empowering metformin with cholecalciferol and taurine supplementation in type 2 diabetic rats

BACKGROUND Type 2 diabetes is one of the most prevalent chronic diseases worldwide,significantly impacting patients'quality of life.Current treatment options like metformin(MET)effectively counteract hyperglycemia but fail to alleviate diabetes-associated complications such as retinopathy,neuropathy,nephropathy,hepatopathy,and cardiovascular diseases.AIM To propose the supplementation of cholecalciferol(CHO)and taurine(TAU)to enhance MET efficacy in controlling diabetes while minimizing the risk of associated complications.METHODS The study involved sixty rats,including ten non-diabetic control rats and fifty experimental rats with type 2 diabetes induced by streptozotocin.The experimental rats were further subdivided into positive control and treatment subgroups.The four treatment groups were randomly allocated to a single MET treatment or MET combined with supplements either CHO,TAU,or both.RESULTS Diabetic rats exhibited elevated levels of glucose,insulin,Homeostasis Model Assessment of Insulin Resistance(HOMA-IR),glycated hemoglobin percentage,lipid markers,aspartate aminotransferase,and malondialdehyde,along with reduced levels of antioxidant enzymes(catalase and superoxide dismutase).The administration of CHO and TAU supplements alongside MET in diabetic rats led to a noticeable recovery of islet mass.The antioxidative,anti-inflammatory,and anti-apoptotic properties of the proposed combination therapy significantly ameliorated the aforementioned abnormalities.CONCLUSION The supplementation of CHO and TAU with MET showed the potential to significantly improve metabolic parameters and protect against diabetic complications through its antioxidative,anti-inflammatory,and antiapoptotic effects.

Postmenopausal Osteoporosis and Osteopenia Management with a Combination of Once-Monthly Oral Ibandronate and Cholecalciferol—A Systematic Review

Postmenopausal osteoporosis and osteopenia are chronic and uncurable conditions that invariably lead to an increased risk of vertebral, hip, and femoral neck fracture if left untreated. Clinical guidelines establish, in general, pharmacological combinations allied to lifestyle changes as the mainstay of their management, and also increasing bone marrow density, lowering fracture risk, and improving quality of life are their main therapeutic goals. The objective of this systematic review was to analyze the available data in the scientific medical literature regarding the role of the ibandronate and cholecalciferol combination in postmenopausal osteoporosis and osteopenia management. Based on our results, we concluded that the above combination is safe and feasible for the clinical control of both conditions.

Vitamin D deficiency in chronic liver disease

Vitamin D is an important secosteroid hormone with known effect on calcium homeostasis,but recently there is increasing recognition that vitamin D also is involved in cell proliferation and differentiation,has immunomodulatory and anti-inflammatory properties.Vitamin D deficiency has been frequently reported in many causes of chronic liver disease and has been associated with the development and evolution of non-alcoholic fatty liver disease(NAFLD)and chronic hepatitis C(CHC)virus infection.The role of vitamin D in the pathogenesis of NAFLD and CHC is not completely known,but it seems that the involvement of vitamin D in the activation and regulation of both innate and adaptive immune systems and its antiproliferative effect may explain its importance in these liver diseases.Published studies provide evidence for routine screening for hypovitaminosis D in patients with liver disease.Further prospectives studies demonstrating the impact of vitamin D replacement in NAFLD and CHC are required.

Association of vitamin D and knee osteoarthritis in younger individuals

BACKGROUND The incidence of primary osteoarthritis knee is gradually increasing among young individuals.The increasing prevalence of obesity,sedentary lifestyle,sporting activity,and vitamin D deficiency(VDD)has been hypothesized for this shifting disease trend.This study was designed to look for the association of serum vitamin D among these young arthritic patients.AIM To look for the association of serum vitamin D in younger knee osteoarthritis(KOA)patients.METHODS In a 2-year observational study,146 non-obese KOA patients of 35-60 years were evaluated clinically(Knee injury and Osteoarthritis Outcome Score,KOOS)and radiologically(Kellegren-Lawrence stage,KL).The serum 25(OH)D level of these patients and 146 normal healthy individuals of same age group were estimated.RESULTS Both the groups were comparable in terms of age and sex.The average serum 25(OH)D level in healthy individuals and KOA patients was 45.83 ng/mL and 34.58 ng/mL,respectively(P<0.001).Inadequate serum 25(OH)D level(<30 ng/mL)was found in 46.57%of KOA patients and 24%of normal healthy participants indicating a significant positive association(odds ratio 2.77,95%CI:1.67-4.54,P<0.001).The 25(OH)D level in KL grade I,II,III and IV was 43.40,30.59,31.56 and 33.93 ng/mL respectively(no difference,P=0.47).Similarly,the KOOS score in sufficient,insufficient and deficient groups were 65.31,60.36 and 65.31,respectively(no difference,P=0.051).CONCLUSION The serum 25(OH)D level is significantly low in younger KOA patients.However,the clinical and radiological severities have no association with serum vitamin D level.

Bones and Crohn’s:No benefit of adding sodium fluoride or ibandronate to calcium and vitamin D

AIM: To compare the effect of calcium and cholecalciferol alone and along with additional sodium fluoride or ibandronate on bone mineral density (BMD) and fractures in patients with Crohn's disease (CD). METHODS: Patients (n =148) with reduced BMD (T-score < -1) were randomized to receive cholecalciferol (1000 IU) and calcium citrate (800 mg) daily alone(group A, n = 32) or along with additional sodium fluoride (25 mg bid) (group B, n = 62) or additional ibandronate (1 mg iv/3-monthly) (group C, n = 54). Dual energy X-ray absorptiometry of the lumbar spine (L1-L4) and proximal right femur and X-rays of the spine were performed at baseline and after 1.0, 2.25 and 3.5 years. Fracture-assessment included visual reading of X-rays and quantitative morphometry of vertebral bodies (T4-L4).RESULTS: One hundred and twenty three (83.1%) patients completed the first year for intention-to-treat (ITT) analysis. Ninety two (62.2%) patients completed the second year and 71 (47.8%) the third year available for per-protocol (PP) analysis. With a significant increase in T-score of the lumbar spine by +0.28 ± 0.35 [95% conf idence interval (CI): 0.162-0.460, P < 0.01], +0.33 ± 0.49 (95% CI: 0.109-0.558, P < 0.01), +0.43 ± 0.47 (95% CI: 0.147-0.708, P < 0.01) in group A, +0.22 ± 0.33 (95% CI: 0.125-0.321, P < 0.01); +0.47 ± 0.60 (95% CI: 0.262-0.676, P < 0.01), +0.51 ± 0.44 (95% CI: 0.338-0.682, P < 0.01) in group B and +0.22 ± 0.38 (95% CI: 0.111-0.329, P < 0.01), +0.36 ± 0.53 (95% CI: 0.147-0.578, P < 0.01), +0.41 ± 0.48 (95% CI: 0.238-0.576, P < 0.01) in group C, respectively, during the 1.0, 2.25 and 3.5 year periods (PP analysis), no treatment regimen was superior in any in- or between-group analyses. In the ITT analysis, similar results in all in- and between-group analyses with a significant in-group but non-significant between-group increase in T-score of the lumbar spine by 0.38 ± 0.46 (group A, P < 0.01), 0.37 ± 0.50 (group B, P < 0.01) and 0.35 ± 0.49 (group C, P < 0.01) was observed. Follow-up in ITT analysis was still 2.65 years. One vertebral fracture in the sodium fluoride group was detected. Study medication was safe and well tolerated. CONCLUSION: Additional sodium fluoride or ibandronate had no benefit over calcium and cholecalciferol alone in managing reduced BMD in CD.

Maternal and infant vitamin D status during lactation: Is latitude important?

Background: The effect of latitude on maternal and infant vitamin D status during lactation is presumed to be strongly associated with higher rates of deficiency in those living at higher latitudes, yet with lifestyle changes, this conclusion may no longer be correct. Objective: To ascertain if higher latitude adversely affects the vitamin D status of lactating women and their fully breastfeeding infants. Study Design/Methods: Fully breastfeeding women and their infants were eligible for participation in this study as part of a larger prospective vitamin D supplementation trial. Women were recruited from two sites of differing latitude: Charleston, SC at 32°N and Rochester, NY at latitude 43°N. Maternal and infant baseline vitamin D status, intact parathyroid hormone (IPTH), serum calcium and phosphorus as a function of site/latitude were measured. The primary outcome was maternal and infant total circulating 25(OH)D at baseline by center/latitude, and the secondary outcome was the percent of women and infants who had achieved a baseline concentration of at least 20 ng/mL, meeting the Institute of Medicine’s definition of sufficiency at 4 to 6 weeks postpartum. Statistical analysis was performed using SAS version 9.3. Results: Higher latitude adversely affected vitamin D status only in lactating Caucasian women. African American and Hispanic women and infants living in Rochester compared to Charleston had improved vitamin D status, an effect that was no longer significant when controlling for socioeconomic factors and season. Overall, there was a significant vitamin D deficiency at baseline in lactating mothers, and a far greater deficiency in their infants. Maternal baseline 25(OH)D concentration remained positively associated with being Caucasian, BMI and summer months. Breastfeeding infant vitamin D status mirrored maternal status and remained positively associated with being Caucasian and summer months. Those infants who had been on a vitamin D supplement at the time of enrollment in the study had markedly improved vitamin D status compared to those infants not on supplement, but represented a significant minority of the cohort. Conclusions: There was a significant vitamin D deficiency among a cohort of women and their infants living at two diverse latitudes—Charleston, SC and Rochester, NY. Given the higher rate of vitamin D deficiency among African American and Hispanic women and their infants living at a lower latitude, conclusions about vitamin D status based on latitude alone may be faulty.

Relationship between body mass index and serum 25-hydroxyvitamin D stronger among Caucasians than African Americans in NHANES adults 2001-2006

The rapid decline in circulating levels of serum 25-hydroxyvitamin D in both African Americans and Caucasians in the US population remains unexplained, and appears to parallel the obesity epidemic. The cross sectional data on 7349 Caucasian and African American adults between 21 and 69 years of age from the continuous National Health and Nutrition Examination Study (NHANES) 2001 to 2006 were used to model by race, with smoothing functions, the true relationship between body mass index (BMI), waist circumference and serum 25-hydroxyvitamin D in men and women. Weighted regressions of determinants of serum 25-hydroxyvitamin D levels were analyzed. Serum 25-hydroxyvitamin D is negatively associated with BMI linearly above an inflection point at 20 kg/m2 and positively associated below a BMI of 20 kg/m2. The gender- and age-adjusted regression coefficients of BMI on 25-hydroxyvitamin D levels demonstrate a 50% lower coefficient (r = –0.18 ng/ml/ BMI unit) among African Americans than among Caucasians (r = –0.36 ng/ml/BMI unit). These relationships were as great in men as in women and were replicated when waist circumference was used as a surrogate for visceral fat levels. The extent to which BMI is a strong predictor of serum 25-hydroxyvitamin D levels depends upon BMI being greater than 20 kg/m2. The hockey stick shape of the BMI 25-hydroxyvitamin D relationship needs to be taken into account when adjusting serum values for BMI. Both this inflection and reduction in serum levels of 25-hydroxyvitamin D in the population may be due to sequestration in an increasing adipose tissue reservoir. The interpretation of serum 25-hydroxyvitamin D levels as a biomarker of vitamin D adequacy requires appropriate adjustment of body fat mass.

Vitamin D, Testosterone, Epigenetics and Pain an Evolving Concept of Neurosignaling, Neuroplasticity and Homeostasis

The thought of exploring a possible relationship between the broad systems of steroid hormone physiology (specifically vitamin D and testosterone) and nocioception was prompted by an unexpectedly frequent personal clinical observation. Patients with chronic pain syndromes or chronic musculoskeletal pain often have low serum levels of vitamin D and testos-terone. Mining for relevant information in Pub Med, Medline and Cochrane Systems Review, three concepts repeatedly emerge that provide a common context for understanding the mechanics of these diverse sys-tems—epigenetic, homeostasis and neuroplasticity. Viewing homeostasis within the framework of epigenetics allows reasoned speculation as to how various human systems interact to maintain integrity and function, while simultaneously responding in a plastic manner to external stimuli. Cell signaling supports normal function by regulating synaptic activity, but can also effect plastic change in the central and peripheral nervous system. This is most commonly achieved by post-translational remodeling of chromatin. There is thus persistent epigenetic change in protein synthesis with all the related downstream effects but without disruption of normal DNA se-quencing. In itself, this may be considered an example of genomic homeo-stasis. Epigenetic mechanisms in nociception and analgesia are active in the paleospinothalamic and neospinothalamic tracts at all levels. Physiologic response to a nociceptive insult, whether mechanical, inflammatory or ischemic, is provided by cell signaling that is significantly enhanced through epigenetic mechanisms at work in nociceptors, Gamma-Aminobutyric Acid (GABA) and glutamate receptors, voltage gated receptors, higher order neurons in the various dorsal horn laminae and proximal nociceptive pro-cessing centers in the brainstem and cortex. The mediators of these direct or epigenetic effects are various ligands also active in signaling, such as free radicals, substance P, a variety of cytokines, growth factors and G proteins, stress responsive proteins, matrix and structural proteins such as reelin and the Jmjd3 gene/enzyme. Calcitriol, the vitamin D receptor and vitamin D Responsive Elements collectively determine regulatory effects of this secosteroid hormone. Agents of homeostasis and plasticity include various D-system specific cytochrome enzymes (CYP 24, CYP 27 A1, B1), as well as more widely active enzymes and protein cell signalers (Jmjd3, Calbindin, BMP), many of which play a role in the nociceptive system. While the highlighted information represents an understanding of complex systems that is currently in its infancy, there are clear results from reliable research at a foundational level. These results are beginning to tell a compelling tale of the homeostasis and plasticity inherent in vitamin D and nociception systems.

The 2^ndStep by Step International Spinal Cord Repair—Combining research Step by Step into multi-pronged approaches for spinal cord repair

On April 26-27, 2013, the Step by Step Foundation hosted the Second International Spinal Cord Repair Meeting at the Fira Barcelona Convention Center in Hospitalet de Llobregat, Spain, highlighting some of the exciting research including clinical trials which show promise for treatments for this devastating disorder. This meeting brought together clinicians, clinical scientists and molecular biologists from more than 10 countries to evaluate current knowledge on clinical, cellular, and biomolecular aspects of spinal cord injury. A major goal of the conference in advancing the translation of research data to the clinic was to promote multi-pronged approaches for therapy of this complex problem.

Evaluation of one-alpha-hydroxy-cholecalciferol alone or in combination with cholecalciferol in Ca-P deficiency diets on development of tibial dyschondroplasia in broiler chickens

This experiment was conducted to determine whether dietary cholecalciferol will alleviate a calcium and phosphorous(Ca-P) deficiency when one-alpha-hydroxy-cholecalciferol,1 a(OH)D_3,is supplemented,and to determine the effects of adequate and inadequate Ca-P when 1 a(OH)D_3 is supplemented and vitamin D_3 is adequate.A total of 144 one-d-old broiler chicks(Ross 308) were allocated to 3 treatments.The dietary treatments were as follows: treatment A,adequate Ca-P + cholecalciferol + 5 mg/kg 1 a(OH)D_3;treatment B,inadequate Ca-P + cholecalciferol + 5 mg/kg 1 a(OH)D_3; treatment C,inadequate Ca-P + 5 mg/kg 1 a(OH)D_3.All diets were mixed with 500 FTU/kg of phytase,and cholecalciferol was provided in 5,000 IU/kg except for treatment C that fed diets without vitamin D_3.The Ca-P levels in the adequate diets were 0.90% Ca,0.66% total phosphorus(t P); 0.75% Ca,0.59% t P; 0.69% Ca,0.54% t P for the starter,grower and finisher periods.At d 42 of age,broilers were inspected for incidence and severity of tibial dyschondroplasia(TD).The results showed that inadequate Ca-P supplementation with cholecalciferol significantly decreased the incidence of TD,score and tibia ash compared with broilers fed the same diet in the absence of cholecalciferol(P < 0.05).The broilers fed inadequate Ca-P diets with cholecalciferol were unable to achieve the same tibia ash and incidence of TD as those fed Ca-P adequate diets(P < 0.05).In conclusion,this trial suggests that broilers fed an inadequate Ca-P diet with 1 a(OH)D_3 and adequate level of cholecalciferol are unable to sufficient bone formation.There was no indication that 1 a(OH)D_3 in the absence of cholecalciferol was effective in reducing TD whereas it could improve tibia ash.

Emulsion-filled gels of soy protein isolate for vehiculation of vitamin D3:Effect of protein solubility on their mechanical and rheological characteristics

The aim of this study was to develop heat-induced gels of soy protein isolate(SPI)filled with Brazil nut oil emulsions encapsulating vitamin D3(VD3).Before gelation,dispersions produced with different SPI concentrations(11-15%,w/w)were subjected to different pretreatments(manual mixing or mechanical stirring at 800 rpm for 10,20,and 30 min)and had their protein solubility quantified.The application of mechanical stirring increased the solubility of proteins and decreased the average particle size,affecting the microstructure(observed by confocal laser scanning microscopy)and rheological properties(evaluated by uniaxial compression and small strain oscillatory tests)of the heat-set gels.The incorporation of emulsions(produced with Brazilian nut oil)into gels formed emulsion filled gels(EFGs),which presented higher Young’s moduli andσH in comparison to non-filled gels(NFGs),indicating that the oil droplets were active within the matrices.The properties of EFGs subjected to small strain oscillatory tests,varied with the pretreatment conditions and SPI concentrations,highlighting the high influence of protein solubility,matrix inhomogeneities,and droplet clustering for determining the properties of such complex systems.Also,the heat-induced emulsion-filled gels of SPI produced were effective in protecting VD3,presenting good retention after 30 days of storage under refrigeration,and represent promising alternative for the production of future food gelled products.