Vitamin D supplementation in breastfed infants from Montréal,Canada: 25-hydroxyvitamin D and bone health effects from a follow-up study at 3 years of age

Summary

Whether infant vitamin D supplementation may have long-term bone benefits is unclear. In this study, breastfed infants who received vitamin dosages greater than 400 IU/day did not have higher bone mineralization at 3 years. This study provides important data to inform pediatric public health recommendations for vitamin D.

Introduction

North American health agencies recommend breastfed infants should be supplemented with 400 IU of vitamin D/day to support bone health. Few studies examined the long-term benefits of early life vitamin D supplementation on bone mineralization. The objective of this study was to determine if a dose-response relationship exists between infant vitamin D supplementation, vitamin D status, and bone outcomes at 3 years of age.

Methods

This was a double-blind randomized trial of 132, 1-month-old healthy, breastfed infants from Montréal, Canada, between 2007 and 2010. In this longitudinal analysis, 87 infants (66 %) returned for follow-up at 3 years of age, between 2010 and 2013. At 1 month of age, participants were randomly assigned to receive oral cholecalciferol (vitamin D₃) supplements of 400, 800, 1200, or 1600 IU/day until 12 months of age. Lumbar spine vertebrae 1–4 (LS) bone mineral density (BMD), LS and whole body bone mineral content (BMC), and mineral accretion were measured by dual-energy x-ray absorptiometry at 3 years.

Results

At follow-up, the treatment groups were similar in terms of diet, sun exposure, and demographics. There were no significant differences among the groups in LS or whole body BMC, BMD, or accretion. Although, 25(OH)D concentrations were not different among the groups, higher doses (1200 and 1600 IU/day) achieved higher 25(OH)D area under the curve from 1 to 36 months vs. 400 IU/day.

Conclusions

This is the first longitudinal follow-up of an infant vitamin D dose-response study which examines bone mineralization at 3 years of age. Dosages higher than 400 IU/day do not appear to provide additional benefits to the bone at follow-up. Larger studies with more ethnically diverse groups are needed to confirm these results.

     

Vitamin D Deficiency Before Bariatric Surgery: Should Supplement Intake Be Routinely Prescribed?

Background

Before bariatric surgery, we demonstrate a 96% rate of vitamin D deficiency in morbidly obese French patients: should supplement intake be routinely prescribed? We conducted a prospective observational study to demonstrate the prevalence of vitamin D deficiency in morbidly obese patients awaiting bariatric surgery.

Methods

Clinical and biological data were collected on 50 successive patients.

Results

Data showed vitamin D deficiency in 96% (25-OH vitamin D = 31 ± 13 nmol/l), with a cut-point of 50 nmol/l. Secondary hyperparathyroidism was found in 44% of patients with hypovitaminosis D (parathyroid hormone (PTH), 59?±?24 pg/ml). Impaired PTH level concerned 89% of this group, considering the cut-point at 30 pg/ml. No significant correlation appeared between vitamin D and calcium or phosphate levels.

Conclusions

Before surgery, we demonstrated a higher incidence of vitamin D deficiency in morbidly obese French patients as compared to the general population. The incidence was also higher than previous American studies. Screening for hypovitaminosis D may routinely be considered in morbid obesity. Long-term observation is, however, needed to assess the advantages and potential side effects of systematic vitamin D supplements.

     

25-Hydroxycholecalciferol response to single oral cholecalciferol loading in the normal weight,overweight, and obese

Summary

After a single cholecalciferol load, peak serum 25-hydroxycholecalciferol (25OHD) is lower in individuals with a higher body mass index (BMI), probably due to it being distributed in a greater volume. Its subsequent disappearance from the serum is slower the higher the individual’s BMI, probably due to the combination of a larger body volume and a slower release into the circulation of vitamin D stored in adipose tissue.

Introduction

The aim of the study is to examine 25-hydroxycholecalciferol (25OHD) response to a single oral load of cholecalciferol in the normal weight, overweight, and obese.

Methods

We considered 55 healthy women aged from 25 to 67 years (mean?±?SD, 50.8?±?9.5) with a BMI ranging from 18.7 to 42 kg/m² (mean?±?SD, 27.1?±?6.0). The sample was divided into three groups by BMI: 20 were normal weight (BMI?≤?25 kg/m²), 21 overweight (25.1?≤?BMI?≤?29.9 kg/ m²), and 14 obese (BMI?≥?30 kg/m²). Each subject was given 300,000 IU of cholecalciferol orally during lunch. A fasting blood test was obtained before cholecalciferol loading and then 7, 30, and 90 days afterwards to measure serum 25OHD, 1,25 dihydroxyvitamin D [1,25 (OH)₂D], parathyroid hormone (PTH), calcium (Ca), and phosphorus (P). Participants’ absolute fat mass was measured using dual energy X-ray absorptiometry (DEXA).

Results

The fat mass of the normal weight subjects was significantly lower than that of the overweight, which in turn was lower than that of the obese participants. Serum 25OHD levels increased significantly in all groups, peaking 1 week after the cholecalciferol load. Peak serum 25OHD levels were lower the higher the individuals’ BMI. After peaking, the 25OHD levels gradually decreased, following a significantly different trend in the three groups. The slope was similar for the overweight and obese, declining significantly more slowly than in the normal weight group. In the sample as a whole, there was a weakly significant negative correlation between fat mass and baseline 25OHD level, while this correlation became strongly significant at all time points after cholecalciferol loading.

Conclusions

The lower peak 25OHD levels seen in the obese and overweight is probably due to the cholecalciferol load being distributed in a larger body volume. The longer persistence of 25OHD in their serum could be due to both their larger body volume and a slower release into the circulation of the vitamin D stored in their adipose tissue.

     

Vitamin D supplementation improves endothelial dysfunction in patients with non-dialysis chronic kidney disease

Purpose

Hypovitaminosis D is common in chronic kidney disease (CKD) and is associated with endothelial dysfunction and cardiovascular events. This study aimed to investigate the effects of vitamin D supplementation on endothelial dysfunction in non-dialysis CKD patients.

Materials and methods

Seventy-one non-dialysis CKD patients with low vitamin D (serum 25(OH)D < 30 ng/mL) were recruited. Patients received oral cholecalciferol 50,000 units once a week for 12 weeks. Changes in endothelial function by brachial artery flow-mediated dilation (FMD), soluble vascular cell adhesion molecule-1 (sVCAM-1), and sE-selectin were studied.

Results

There was a significant increase in serum levels of 25(OH)D after cholecalciferol supplementation (33.7 ± 12.1 vs. 13.2 ± 5.4 ng/mL, P < 0.001). Multivariable regression analysis showed that higher proteinuria (β = ? 0.548, P < 0.001) and lower levels of 25(OH)D (β = 0.360, P < 0.001) at baseline were related to lower 25(OH)D level after supplementation. FMD increased significantly from 4.4 ± 1.3 to 5.1 ± 1.5% (P < 0.001), and soluble endothelial biomarkers decreased: sVCAM-1 from 926.9 ± 158.0 to 867.0 ± 129.0 ng/mL (P < 0.001), and sE-selectin 69.7 ± 15.8 to 63.3 ± 14.7 ng/mL (P < 0.001).

Conclusions

Vitamin D supplementation can improve endothelial dysfunction in pre-dialysis CKD patients.

     

Effect of concomitant vitamin D deficiency or insufficiency on lumbar spine volumetric bone mineral density and trabecular bone score in primary hyperparathyroidism

Summary

Lower vitamin D and higher parathyroid hormone (PTH) levels are associated with higher volumetric BMD and bone strength at the lumbar spine as measured by central quantitative computed tomography in primary hyperparathyroidism (PHPT), but there are no differences in bone microarchitecture as measured by trabecular bone score (TBS).

Introduction

The purpose of this study was to evaluate the association between 25-hydroxyvitamin D (25OHD) and volumetric bone mineral density (vBMD) and the TBS at the lumbar spine (LS) in PHPT.

Methods

This is a cross-sectional analysis of PHPT patients with and without low 25OHD. We measured vBMD with quantitative computed tomography (cQCT) and TBS by dual-energy X-ray absorptiometry (DXA) at the LS in 52 and 88 participants, respectively.

Results

In the cQCT cohort, those with lower vitamin D (<20 vs. 20-29 vs. ≥30 ng/ml) tended to be younger (p?=?0.05), were less likely to use vitamin D supplementation (p?<?0.01), and had better renal function (p?=?0.03). Those with 25OHD <20 ng/ml had 80 and 126 % higher serum PTH levels respectively vs. those with 25OHD 20–29 ng/ml (p?=?0.002) and 25OHD ≥30 ng/ml (p?<?0.0001). Covariate-adjusted integral and trabecular vBMD were higher in those with 25OHD 20–29 vs. those with 25OHD ≥30 ng/ml, but those with 25OHD <20 did not differ. Because there were few participants with 25OHD deficiency, we also compared those with vitamin D <30 vs. ≥30 ng/ml. Covariate-adjusted integral and trabecular vBMD were 23 and 30 % higher respectively (both p?<?0.05) in those with vitamin D <30 vs. ≥30 ng/ml. TBS was in the partially degraded range but did not differ by vitamin D status.

Conclusion

In mild PHPT, lower 25OHD is associated with higher PTH, but vitamin D deficiency and insufficiency using current clinical thresholds did not adversely affect lumbar spine skeletal health in PHPT. Further work is needed to determine if higher vBMD in those with lower vitamin D is due to an anabolic effect of PTH.

     

Vitamin D deficiency and seasonal variation over the years in São Paulo,Brazil

Summary

Brazil is a tropical/subtropical geographic area with elevated ultraviolet (UV) radiation. We report very high prevalence of vitamin D deficiency in a large database of Brazilian subjects and show seasonal and reciprocal relationship between vitamin D and parathyroid hormone (PTH) over the years in this tropical area.

Introduction

We aim to examine the prevalence of vitamin D deficiency, characterize the temporal relationship between 25-hydroxyvitamin D levels (25(OH)D) and intact PTH (iPTH) according to seasons, and investigate potential associations between 25(OH)D levels and extra-skeletal outcomes in a Brazilian population.

Methods

We retrospectively determined population weekly mean concentrations of unpaired 25(OH)D and iPTH using 39,004 laboratory results of Brazilian individuals of both genders aged 2 to 95 years. The 25(OH)D and iPTH distributions were normalized, and the means fit with a sinusoidal function. Potential associations between 25(OH)D serum levels and inflammatory markers, fasting glucose, HbA1c and Homeostasis Model Assessment index (HOMA) were examined.

Results

Of the samples, 33.9 % had 25(OH)D serum concentrations lower than 20 ng/mL, while the vast majority (70.7 %) were found to be vitamin D deficient or insufficient (<30 ng/mL). Vitamin D deficiency was significantly higher during the winter as compared to the summer (38.4 % <20 ng/mL and 75.5 % <30 ng/mL versus 23.3 % <20 ng/mL and 62.5 % <30 ng/mL, respectively; p?<?0.001). Seasonal variation was observed for both 25(OH)D and iPTH. 25(OH)D peaks occurred in March and troughs in September. iPTH levels showed an inverted pattern of peaks and troughs with a delay of 1?±?5 week. 25(OH)D was significantly associated with inflammatory markers but not with glucose homeostasis.

Conclusions

A sinusoidal interrelationship has been detected between vitamin D and PTH in this tropical population. A large percentage of the individuals showed vitamin D deficiency. Public health strategies are needed to better understand and manage this very high and apparently contradictory prevalence of vitamin D deficiency.

     

Vitamin D deficiency in adult fracture patients: prevalence and risk factors

Purpose

Although vitamin D levels are not routinely monitored in outpatient fracture patients, identification of fracture patients with a deficient vitamin D status may be clinically relevant because of the potential role of vitamin D in fracture healing. This study aimed to determine the prevalence of and risk factors for vitamin D deficiency in non-operatively treated adult fracture patients.

Patients and methods

Vitamin D levels were determined in a cross-sectional study of adult patients, who were treated non-operatively for a fracture of the upper or lower extremity in the outpatient clinic of a level 1 trauma center, during one calendar year. Potential risk factors for (severe) vitamin D deficiency were analyzed using multivariable logistic regression analysis.

Results

A total of 208 men and 319 women with a mean age of 49.7 years (SD 19.9) were included. In this population, 71 % had a serum calcidiol <75 nmol/L, 40 % were vitamin D deficient (serum calcidiol <50 nmol/L) and 11 % were severely vitamin D deficient (serum calcidiol <25 nmol/L). Smoking and season (winter and spring) were independent risk factors for vitamin D deficiency. An increasing age, a non-Caucasian skin type, winter and smoking were identified as independent risk factors for severe vitamin D deficiency. The use of vitamin D, alcohol consumption and higher average daily sun exposure were independent protective factors against (severe) vitamin D deficiency.

Conclusion

Given the potential role of vitamin D in fracture healing, clinicians treating adult fracture patients should be aware of the frequent presence of vitamin D deficiency during the winter, especially in smoking and non-Caucasian patients. Research on the effect of vitamin D deficiency or supplementation on fracture healing is needed, before suggesting routine monitoring or supplementation.

     

Risk of Biliary Events After Selective Cholecystectomy During Biliopancreatic Diversion with Duodenal Switch

Background

Approximately 20 % of adults over 40 years of age in the USA develop cholelithiasis (Topart et al. Surg Obes Relat Dis. 9(4):526–30, 2013). Despite a higher incidence of biliary complications reported in postbariatric patients, it remains controversial whether simultaneous routine cholecystectomy should be performed during biliopancreatic diversion and duodenal switch (BPD/DS) or if a selective approach is more appropriate. The aim of this study was to evaluate incidence of biliary complications in patients who underwent BPD/DS without simultaneous cholecystectomy.

Methods

Retrospective review of all patients who underwent BPD/DS between 2006 and 2012 was performed.

Results

A total of 361 consecutive patients were included in the study with mean age of 44.8 years (range 20–72), mean body weight of 317.2 lbs (range 205–547), and average body mass index (BMI) of 50.5 kg/m² (range 34–71.4). Ninety-seven patients were males (26.8 %). Out of 239 patients who still had their gallbladder after the BPD/DS, 52 patients (22.7 %) developed subsequent biliary symptoms (13 patients (5.4 %) in the first year, 25 (11 %) in the second year, and 14 (6.1 %) beyond the second year). During the study period, 40 patients eventually underwent elective laparoscopic cholecystectomy, and 11 had urgent cholecystectomy (9 laparoscopic and 2 open). One patient underwent open common bile duct exploration for ascending cholangitis. Average follow-up was 31 months (12–72 months) with follow-up rate of 95.6 % at 12 months and 92.8 % at 18 months.

Conclusions

Leaving normal gallbladder in situ after BPD/DS is associated with an acceptable risk of biliary events. Risk of developing common bile duct stones is low; however, it may create treatment challenges.

     

Low serum 25-hydroxyvitamin D is associated with increased risk of stress fracture during Royal Marine recruit training

Summary

The aim of this study was to investigate vitamin D status and stress fracture risk during Royal Marine military training. Poor vitamin D status was associated with an increased risk of stress fracture. Vitamin D supplementation may help to reduce stress fracture risk in male military recruits with low vitamin D status.

Introduction

Stress fracture is a common overuse injury in military recruits, including Royal Marine (RM) training in the UK. RM training is recognised as one of the most arduous basic training programmes in the world. Associations have been reported between serum 25-hydroxyvitamin D (25(OH)D) and risk of stress fracture, but the threshold of 25(OH)D for this effect remains unclear. We aimed to determine if serum 25(OH)D concentrations were associated with stress fracture risk during RM training.

Methods

We prospectively followed 1082 RM recruits (males aged 16–32 years) through the 32-week RM training programme. Troops started training between September and July. Height, body weight and aerobic fitness were assessed at week 1. Venous blood samples were drawn at weeks 1, 15 and 32. Serum samples were analysed for 25(OH)D and parathyroid hormone (PTH).

Results

Seventy-eight recruits (7.2 %) suffered a total of 92 stress fractures. Recruits with a baseline serum 25(OH)D concentration below 50 nmol L^?1 had a higher incidence of stress fracture than recruits with 25(OH)D concentration above this threshold (χ² ₍₁₎?=?3.564, p?=?0.042; odds ratio 1.6 (95 % confidence interval (CI) 1.0–2.6)). Baseline serum 25(OH)D varied from 47.0?±?23.7 nmol L^?1 in February, to 97.3?±?24.6 nmol L^?1 in July (overall mean 69.2?±?29.2 nmol L^?1, n?=?1016). There were weak inverse correlations between serum 25(OH)D and PTH concentrations at week 15 (r?=??0.209, p?<?0.001) and week 32 (r?=??0.214, p?<?0.001), but not at baseline.

Conclusion

Baseline serum 25(OH)D concentration below 50 nmol L^?1 was associated with an increased risk of stress fracture. Further studies into the effects of vitamin D supplementation on stress fracture risk are certainly warranted.

     

Serum 25-hydroxyvitamin D,parathyroid hormone,calcium intake,and bone mineral density in Spanish adults

Summary

Vitamin D insufficiency is very common among Spanish community-dwelling adult subjects. A threshold of serum 25(OH)D around 30 ng/ml would be necessary for the prevention of secondary hyperparathyroidism and hip bone loss in our population, regardless of the dairy calcium ingestion.

Introduction

This study aims to assess 25-hydroxyvitamin D—25(OH)D—status in Spanish adult subjects and to analyze its relationships with serum PTH levels, calcium intake, and bone mineral density (BMD).

Methods

A total of 1811 individuals (1154 postmenopausal women and 657 men) aged 44–93 years participated in the study. Serum 25(OH)D, intact parathyroid hormone (PTH), aminoterminal propeptide of type I collagen (P1NP), and C-terminal telopeptide of type I collagen (β-CTX) levels were measured by electrochemiluminescence. BMD was determined by dual x-ray absorptiometry (DXA) at lumbar spine, femoral neck, and total hip.

Results

Serum 25(OH)D levels were below 10, 20, and 30 ng/ml in 5, 40, and 83 % of participants, respectively. There was a significant seasonal difference in mean serum 25(OH)D, with higher levels in summer–autumn. In multivariate analysis, 25(OH)D levels were negatively correlated with age, serum PTH and creatinine, body mass index, smoking, alcohol intake, and a number of chronic diseases, but positively with dairy calcium intake. The magnitude of the difference in serum PTH according to 25(OH)D quartiles was not influenced by calcium intake. A threshold of serum 25(OH)D around 30 ng/ml was observed for serum PTH and hip BMD.

Conclusions

Vitamin D insufficiency is very common among Spanish community-dwelling adult subjects. A threshold of serum 25(OH)D around 30 ng/ml would be necessary for the prevention of secondary hyperparathyroidism and hip bone loss in our population, regardless of the dairy calcium ingestion. Programs to improve vitamin D status may be required in our country.

     

Patient-Reported Adherence to Empiric Vitamin/Mineral Supplementation and Related Nutrient Deficiencies After Roux-en-Y Gastric Bypass

Background

Roux-en-Y gastric bypass (RYGB) is associated with nutrient deficiencies, but the optimal supplement regimen remains unclear. We assessed patient-reported adherence to and efficacy of Mayo Clinic’s post-RYGB vitamin/mineral supplement protocol and the related incidence of common nutrient deficiencies.

Methods

Data were collected on 287 obese patients who underwent RYGB. Patient-reported supplement adherence was assessed via medication/supplement lists generated by medication reconciliation in hospital dismissal summaries and clinic notes at 6, 12, and 18–36 months postsurgery. Deficiencies were assessed via measurements of hemoglobin, ferritin, 25-hydroxyvitamin D, and vitamins A, E, and B₁₂ in the setting of our supplementation protocol.

Results

Patient-reported adherence to multivitamin/minerals and subcutaneous vitamin B₁₂ was sustained in >92 % of patients, correlating with low rates of vitamin A, E, and B₁₂ deficiencies (4.9, 0, and 3.7 %, respectively). Rates of calcium supplementation decreased (94.1 to 78.7 %) while rates of vitamin D and iron use increased over time (39.7 to 65.8 and 6.3 to 23.1 %, respectively). At 18–36 months, vitamin D deficiency persisted in 16.2 % of patients, iron deficiency in 6.7 % of women and 17.2 % of men, and anemia in 12.2 % of women and 34.3 % of men.

Conclusion

Compared to previous reports, we found a lower prevalence of micronutrient deficiencies and excellent patient-reported adherence to a standardized multivitamin/mineral and vitamin B₁₂ regimen. Continued prevalence of vitamin D deficiency prompts consideration of standardized vitamin D supplementation after RYGB. Anemia and iron deficiency were observed at lower rates than previously reported, but were more common in men compared to women.

     

Can Composite Nutritional Supplement Based on the Current Guidelines Prevent Vitamin and Mineral Deficiency After Weight Loss Surgery?

Background

Nutritional deficiencies occur after weight loss surgery. Despite knowledge of nutritional risk, there is little uniformity of postoperative vitamin and mineral supplementation. The objective of this study was to evaluate a composite supplement based on the clinical practice guidelines proposed in 2008 regarding vitamin and mineral supplementation after Roux-en-Y gastric bypass. The composite included iron (Fe) and calcium as well.

Methods

A retrospective chart review of 309 patients undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB) was evaluated for the development of deficiencies in iron and vitamins A, B₁, B₁₂, and D. Patients were instructed to take a custom vitamin and mineral supplement that was based on society-approved guidelines. The clinical practice guidelines were modified to include 1600 international units (IU) of vitamin D₃ instead of the recommended 800 IU.

Results

The compliant patients’ deficiency rates were significantly lower than those of the noncompliant patients for iron (p?=?0.001), vitamin A (p?=?0.01), vitamin B₁₂ (p?≈?0.02), and vitamin D (p?<?0.0001). Women’s menstrual status did not significantly influence the development of iron deficiency.

Conclusions

Use of a composite based on guidelines proposed by the AACE, TOS, and the ASMBS appears to be effective for preventing iron and vitamins A, B₁, B₁₂, and D deficiencies in the LRYGB patients during the first postoperative year. Separation of calcium and Fe does not need to be mandatory. Even with simplification, compliance is far from universal.

     

Vitamin D and prostate cancer prognosis: a Mendelian randomization study

Purpose

Decreased vitamin D levels have been associated with prostate cancer, but it is unclear whether this association is causal. A functional single-nucleotide polymorphism (SNP) in the group-specific component (GC) gene (T > G, rs2282679) has been associated with 25-hydroxy (25-OH) vitamin D and 1.25 dihydroxy (1.25-OH2) vitamin D levels.

Methods

To examine the hypothesized inverse relationship between vitamin D status and prostate cancer, we studied the association between this SNP and prostate cancer outcome in the prospective PROCAGENE study comprising 702 prostate cancer patients with a median follow-up of 82 months.

Results

GC rs2282679 genotypes were not associated with biochemical recurrence [hazard ratios (HR) 0.91, 95 % confidence interval (CI) 0.73–1.12; p = 0.36], development of metastases (HR 1.20, 95 % CI 0.88–1.63; p = 0.25) or overall survival (HR 1.10; 95 % CI 0.84–1.43; p = 0.50).

Conclusions

A causal role of vitamin D status, as reflected by GC rs2282679 genotype, in disease progression and mortality in prostate cancer patients is unlikely.

     

Accentuated hyperparathyroidism in type II Bartter syndrome

Background

Bartter syndrome (BS) may be associated with different degrees of hypercalciuria, but marked parathyroid hormone (PTH) abnormalities have not been described.

Methods

We compared clinical and laboratory data of patients with either ROMK-deficient type II BS (n?=?14) or Barttin-deficient type IV BS (n?=?20).

Results

Only BS-IV patients remained mildly hypokalemic in spite of a higher need for potassium supplementation. Estimated glomerular filtration rate (eGFR) was mildly decreased in only four BS-IV patients. Average PTH values were significantly higher in BS-II (160.6?±?85.8 vs. 92.5?±?48 pg/ml in BS-IV, p?=?0.006). In both groups, there was a positive correlation between age and log(PTH). Levels of 25(OH) vitamin D were not different. Total serum calcium was lower (within normal limits) and age-related serum phosphate (Pi)-SDS was increased in BS-II (1.19?±?0.71 vs. 0.01?±?1.04 in BS-IV, p?<?0.001). The GFR threshold for Pi reabsorption was higher in BS-II (5.63?±?1.25 vs. 4.36?±?0.98, p?=?0.002). Spot urine calcium/creatinine ratio and nephrocalcinosis rate (100 vs. 16 %) were higher in the BS-II group.

Conclusions

PTH, serum Pi levels, and urinary threshold for Pi reabsorption are significantly elevated in type II vs. type IV BS, suggesting a PTH resistance state. This may be a response to more severe long-standing hypercalciuria, leading to a higher rate of nephrocalcinosis in BS-II.

     

Vitamins,metabolomics, and prostate cancer

Purpose

How micronutrients might influence risk of developing adenocarcinoma of the prostate has been the focus of a large body of research (especially regarding vitamins E, A, and D). Metabolomic profiling has the potential to discover molecular species relevant to prostate cancer etiology, early detection, and prevention, and may help elucidate the biologic mechanisms through which vitamins influence prostate cancer risk.

Methods

Prostate cancer risk data related to vitamins E, A, and D and metabolomic profiling from clinical, cohort, and nested case–control studies, along with randomized controlled trials, are examined and summarized, along with recent metabolomic data of the vitamin phenotypes.

Results

Higher vitamin E serologic status is associated with lower prostate cancer risk, and vitamin E genetic variant data support this. By contrast, controlled vitamin E supplementation trials have had mixed results based on differing designs and dosages. Beta-carotene supplementation (in smokers) and higher circulating retinol and 25-hydroxy-vitamin D concentrations appear related to elevated prostate cancer risk. Our prospective metabolomic profiling of fasting serum collected 1–20 years prior to clinical diagnoses found reduced lipid and energy/TCA cycle metabolites, including inositol-1-phosphate, lysolipids, alpha-ketoglutarate, and citrate, significantly associated with lower risk of aggressive disease.

Conclusions

Several active leads exist regarding the role of micronutrients and metabolites in prostate cancer carcinogenesis and risk. How vitamins D and A may adversely impact risk, and whether low-dose vitamin E supplementation remains a viable preventive approach, require further study.

     

Low bone mineral density for age/osteoporosis in triple A syndrome—an overlooked symptom of unexplained etiology

Summary

Triple A syndrome (alacrima, achalasia, adrenal failure, progressive neurodegenerative disease) is caused by mutations in the AAAS gene which encodes the protein alacrima achalasia adrenal insufficiency neurologic disorder (ALADIN). Our investigation suggests that low bone mineral density (BMD) for age/osteoporosis could be a common but overlooked symptom of unexplained etiology in this rare multisystemic disease.

Introduction

The purpose of this study is to evaluate incidence and etiology of BMD for age/osteoporosis, a possibly overlooked symptom in triple A syndrome.

Methods

Dual-energy X-ray absorptiometry (DXA) of the femoral neck, total hip, lumbar spine, and radius, bone turnover markers, minerals, total alkaline phosphatase (ALP), 25-hydroxy vitamin D (25-OHD), 1,25-dihydroxy vitamin D (1,25-OH2D), intact parathyroid hormone (PTH), and adrenal androgens (dehydroepiandrosterone sulfate (DHEAS) and androstenedione) were measured in five male and four female patients.

Results

At time of diagnosis, low BMD for age was suspected on X-ray in seven of nine patients aged 2–11 years (not performed in two patients); normal levels of minerals and ALP were found in nine patients and low levels of adrenal androgens in eight patients (not measured in one patient). Reevaluation 5–35 years after introduction of 12 mg/m²/day hydrocortisone showed low BMD for age in two children, osteopenia in one, and osteoporosis in six adults. Normal levels of minerals, ALP, PTH, 1,25-OH2D, procollagen type 1, crosslaps, and osteocalcin were found in all patients. Low levels of adrenal androgens were found in all and 25OHD deficiency in six patients. Body mass index was <25 % for age and sex in eight of nine patients.

Conclusion

Low BMD for age/osteoporosis in our patients probably is not a result of glucocorticoid therapy but could be the consequence of low level of adrenal androgens, neurological impairment causing physical inactivity, inadequate sun exposure, and protein malnutrition secondary to achalasia. Considering ubiquitous ALADIN expression, low BMD/osteoporosis may be a primary phenotypic feature of the disease. Besides optimizing glucocorticoid dose, physical activity, adequate sun exposure, appropriate nutrition, and vitamin D supplementation, therapy with DHEA should be considered.

     

Oral Vitamin B<Subscript>12</Subscript> Supplementation After Roux-en-Y Gastric Bypass: a Systematic Review

Background

Many respectable guidelines recommend lifelong vitamin B₁₂ injections for Roux-en-Y gastric bypass (RYGB) patients in the absence of lack of consensus on the efficacy of oral route of prophylaxis and the appropriate doses needed for this purpose. The purpose of this review was to examine the published English language scientific literature in accordance with PRISMA principles to find out if orally given vitamin B₁₂ is adequate for prophylactic purposes in RYGB patients and the appropriate dosages needed for this purpose if it is.

Methods

We examined the PubMed database for all English language articles examining various doses of oral vitamin B₁₂ supplementation after proximal RYGB in adult patients. The search revealed 19 such articles.

Results

The data suggest that oral vitamin B₁₂ supplementation doses of ≤?15 μg daily are insufficient to prevent deficiency in RYGB patients. Higher supplementation doses show better results and it appears that a dose of 600.0 μg vitamin B₁₂ daily is superior to 350.0 μg daily suggesting an incremental dose-response curve. It further appears that supplementation doses of 1000.0 μg vitamin B₁₂ daily lead to an increase in B₁₂ levels and are sufficient for the prevention of its deficiency in most RYGB patients.

Conclusion

The review finds that oral supplementation doses of ≤?15 μg vitamin B₁₂ daily are inadequate for prophylaxis of vitamin B₁₂ deficiency in adult RYGB patients but doses of 1000 μg vitamin B₁₂ daily might be adequate. Future studies need to examine this and even higher oral doses for vitamin B₁₂ supplementation for patients undergoing RYGB.

     

Vitamin D in incident nephrotic syndrome: a Midwest Pediatric Nephrology Consortium study

Background

Cross-sectional studies of children with prevalent nephrotic syndrome (NS) have shown 25-vitamin D (25(OH)D) deficiency rates of 20–100 %. Information on 25(OH)D status in incident patients or following remission is limited. This study aimed to assess 25(OH)D status of incident idiopathic NS children at presentation and longitudinally with short-term observation.

Methods

Multicenter longitudinal study of children (2–18 years old) from 14 centers across the Midwest Pediatric Nephrology Consortium with incident idiopathic NS. 25(OH)D levels were assessed at diagnosis and 3 months later.

Results

Sixty-one children, median age 5 (3, 11) years, completed baseline visit and 51 completed second visit labs. All 61 (100 %) had 25(OH)D?<?20 ng/ml at diagnosis. Twenty-seven (53 %) had 25(OH)D?<?20 ng/ml at follow-up. Fourteen (28 %) children were steroid resistant. Univariate analysis showed that children prescribed vitamin D supplements were less likely to have 25(OH)D deficiency at follow-up (OR 0.2, 95 % CI 0.04, 0.6). Steroid response, age, and season did not predict 25(OH)D deficiency. Multivariable linear regression modeling showed higher 25(OH)D levels at follow-up by 13.2 ng/ml (SE 4.6, p?<?0.01) in children supplemented with vitamin D.

Conclusions

In this incident idiopathic NS cohort, all children at diagnosis had 25(OH)D deficiency and the majority continued to have a deficiency at 2–4 months. Supplemental vitamin D decreased the odds of 25(OH)D deficiency at follow-up, supporting a role for supplementation in incident NS.

     

Maintenance of Multivitamin Supplements After Sleeve Gastrectomy

Introduction

After all bariatric procedures, multivitamin supplements are uniformly prescribed to minimize eventual deficiencies. These supplements are usually maintained long time, even during the whole life after malabsorptive techniques, while these are maintained at least during 1 year after restrictive procedures. Given that sleeve gastrectomy does not alter intestinal absorption, the supplements are possibly unnecessary, once the patient can take an adequate diet.

Patients and Methods

A prospective randomized study of patients undergoing a laparoscopic sleeve gastrectomy was performed. Patients were randomized into two groups: those patients receiving the multivitamin supplement (Multicentrum, Pfizer, 1 tablet/day) during 3 months (group 1) and those receiving the supplement during 12 months (group 2). Laboratory data were recorded: vitamins (D, B12 and folic acid) and oligoelements (calcium, iron, phosphorus, magnesium and zinc) at 3, 6 and 12 months after surgery.

Results

Eighty patients were included, 40 in each group. At 3 months, 7.5 % of the patients presented iron deficiency and 2.5 % ferritin one, similarly in both groups, that was corrected with specific extra iron supplements. At 6 months, one patient (2.5 %) in group 1 presented iron deficiency and one in group 2 vitamin D deficiency (NS). At 12 months, only one patient in group 2 presented vitamin D deficiency, treated with specific supplements.

Conclusion

The maintenance of multivitamin supplements more than 3 months postoperatively seems to be of no benefit. It is preferable monitoring laboratory values and adding specific supplements when necessary.

ClinicalTrials.gov Identifier

NCT02620137