Serum vitamins and homocysteine levels in autoimmune liver disease: A systematic review and meta-analysis.

OBJECTIVE: Vitamins and homocysteine (Hcy) are involved in liver metabolism and related to the pathogenesis of autoimmune liver disease (AILD), but consensus is lacking. This study aims to systematically summarize relevant evidence to clarify the association of serum vitamins and Hcy levels with AILD. METHODS: The English and Chinese literature was searched until August 29, 2023. Studies were included if they were observational studies of investigating serum vitamins and Hcy levels in patients with AILD and their healthy comparisons. Quality assessment was performed by using the Newcastle-Ottawa Scale, and a meta-analysis was conducted using ReviewManager 5.3. The protocol was registered in the international prospective register of systematic reviews (PROSPERO), with registration number CRD42023455367. RESULTS: A total of 25 case-control studies comprising 3487 patients (1673 patients and 1814 healthy controls) were included for analysis. There were 548 autoimmune hepatitis (AIH) cases, 1106 primary biliary cholangitis (PBC) cases, and 19 primary sclerosing cholangitis (PSC) cases. We found that serum A and E were decreased in both AIH and PBC/PSC; but vitamin C was reduced only in patients with PBC, not AIH. In addition, decreased content of 25(OH)D3 was found in both AIH and PBC. However, levels of 25(OH)D did not differ between the patients and controls, and were independent of disease types and the country. Only one study that met the inclusion criteria reported vitamin B6, B9, B12, and Hcy changes, and found that vitamin B6 and B9 were significantly decreased in patients with PBC, while serum vitamin B12 and Hcy levels were significantly elevated in them. One eligible study each confirmed a reduction in plasma vitamin K1 and 1,25(OH)2D3 in patients with PBC. CONCLUSION: Most vitamins are deficient in AILD, so appropriate vitamin supplementation should be necessary. Further studies with larger sample sizes are needed to validate these findings.

Antioxidants, minerals and vitamins in relation to Crohn's disease and ulcerative colitis: A Mendelian randomization study.

BACKGROUND: Evidence for antioxidants, minerals and vitamins in relation to the risk of Crohn's disease (CD) and ulcerative colitis (UC) is limited and inconsistent. This mendelian randomization (MR) study aimed to examine the causal associations of circulating levels of antioxidants, minerals and vitamins with CD and UC. METHODS: Single-nucleotide polymorphisms associated with antioxidants (beta-carotene, lycopene and uric acid), minerals (copper, calcium, iron, magnesium, phosphorus, zinc and selenium), and vitamins (folate, vitamins A, B6, B12, C, D, E and K1) were employed as instrumental variables. Genetic associations with CD and UC were extracted from the UK Biobank, the FinnGen study and the International Inflammatory Bowel Disease Genetics Consortium. The inverse variance weighted method and sensitivity analyses were performed. RESULTS: Genetically predicted higher lycopene (OR = 0.94, 95% CI: 0.91-0.97), vitamins D (OR = 0.65, 95% CI: 0.54-0.79) and K1 (OR = 0.93, 95% CI: 0.90-0.97) levels were inversely associated with CD risk, whereas genetically predicted higher magnesium (OR = 1.53, 95% CI: 1.23-1.90) levels were positively associated with CD risk. Higher levels of genetically predicted lycopene (OR = 0.91, 95% CI: 0.88-0.95), phosphorus (OR = 0.69, 95% CI: 0.58-0.82), selenium (OR = 0.91, 95% CI: 0.85-0.97), zinc (OR = 0.91, 95% CI: 0.89-0.94), folate (OR = 0.71, 95% CI: 0.56-0.92) and vitamin E (OR = 0.78, 95% CI: 0.69-0.88) were associated with reduced UC risk, whereas genetically predicted high levels of calcium (OR = 1.46, 95% CI: 1.22-1.76) and magnesium (OR = 1.24, 95% CI: 1.03-1.49) were associated with increased risk of UC. CONCLUSIONS: Our study provided evidence that circulating levels of antioxidants, minerals and vitamins might be causally linked to the development of IBD.

Plasma Levels of Bioactive Vitamin D and A5 Ligands Positively Correlate with Clinical Atopic Dermatitis Markers.

BACKGROUND: Over the past decade, several controversial studies described a relationship between vitamin D and atopic diseases. Low plasma vitamin D levels or even vitamin D deficiency was associated with an increased incidence of atopic disease, postulating that a higher dietary intake of vitamin D may be a beneficial strategy against atopic diseases such as atopic dermatitis (AD). OBJECTIVE: Our aim was to determine the relationship between plasma 25-hydroxyvitamin D3 (25(OH)D3) levels, the levels of the ligand of the vitamin D receptor (VDR) heterodimerization partner as well as the retinoid X receptor (RXR) and the active vitamin A5 derivative 9-cis-13,14-dihydroretinoic acid (9CDHRA) and AD severity. METHODS/RESULTS: Samples from AD patients (n = 20) and healthy volunteers (n = 20) were assessed. In our study, the frequently measured VDR ligand precursor 25(OH)D3 in addition to the VDR-ligand 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 9CDHRA displayed no different levels when compared with the plasma of AD patients and healthy volunteers. When performing further correlation studies focusing on AD patients, plasma 25(OH)D3 levels showed a negative correlation with eosinophils in blood (EOS) and SCORing Atopic Dermatitis (SCORAD) values, while 1,25(OH)2D3 and 9CDHRA levels correlated positively with plasma IgE, EOS, and SCORAD values. CONCLUSION: In consequence, the metabolic activation of vitamin D from 25(OH)D3 towards 1,25(OH)2D3 as well as the co-liganding of the RXR by 9CDHRA may be an important signalling mechanism, an important marker for AD development and severity as well as the basis for novel nutritional and pharmaceutical AD treatment options.

Vitamin D in Alzheimer's Disease: Low Levels in Cerebrospinal Fluid Despite Normal Amounts in Serum.

BACKGROUND: Vitamin D insufficiency has been suggested as a dementia risk factor. OBJECTIVE: In this cross-sectional, explorative study we investigated whether levels of vitamin D in cerebrospinal fluid (CSF) are lower in patients with positive biomarkers of Alzheimer's disease (AD) compared to cognitively healthy controls and whether polymorphisms of the vitamin D receptor (VDR) gene, FokI, BsmI, ApaI, and TaqI, are associated with levels of vitamin D in CSF and cognition. METHODS: We included 100 patients≥65 years assessed for cognitive impairment and 76 cognitively healthy controls. Levels of 25-hydroxyvitamin D (25(OH)D) in both serum and CSF, and VDR polymorphisms were analyzed. RESULTS: The mean level of 25(OH)D in serum was 78.6 (SD 28.9) nmol/l. While serum levels of 25(OH)D were not significantly different between the groups, CSF levels of 25(OH)D were significantly lower in patients with positive AD core biomarkers (p = 0.001) compared to patients without such biomarkers. Individuals with the BsmI major homozygote genotype had significantly lower results on a 10-word delayed recall test (p = 0.044) and verbal fluency test (p = 0.013), and individuals with the TaqI major homozygote genotype had significantly lower results on a verbal fluency test (p = 0.030) compared to individuals with the corresponding minor homozygote genotype. CONCLUSION: Patients with positive AD core biomarkers have low CSF levels of 25(OH)D, despite sufficient serum levels. CSF levels of 25(OH)D do not seem to be affected by any of the four VDR gene polymorphisms. TaqI and BsmI major homozygote genotypes might be at increased risk for development of cognitive decline.

Changes in adipokine levels and metabolic profiles following bariatric surgery.

BACKGROUND: Bariatric surgery is considered to be the most effective treatment option for weight reduction in obese patients. Abdominal obesity is frequently accompanied by metabolic syndrome (MS). Adipokines are cell signaling proteins that have direct impact upon the metabolic homeostasis. The purpose of this analysis was to evaluate the effect of bariatric surgery, including laparoscopic sleeve gastrectomy (LSG) and laparoscopic gastric bypass (LRYGB) on the adipokine levels and metabolic profile as well as MS and status of type 2 diabetes (T2D). METHODS: We analyzed anthropometric parameters, blood levels of adipokines, vitamins, lipids and inflammatory markers in 30 bariatric surgery patients with obesity of class II or III 1 month before and 1 year after surgery as well as in 60 obese patients from general practice (GP) and 15 patients with normal body mass (control). RESULTS: The BMI was significantly higher among patients before surgery and GP patients in comparison to control and post-surgery patients. The levels of glucose, cholesterol and LDL-cholesterol, triglyceride and hs-CRP were the highest in patients before surgery but decreased significantly after surgery, while the level of HDL-cholesterol increased after surgery. The levels of adiponectin increased and that of leptin decreased after surgery. The significant difference in the concentration of resistin was revealed between LSG and LRYGB methods. The relationship between resistin and vitamin D was also found. The patients with MS and T2D displayed significantly greater reduction in lipid markers and adipokine levels than the rest of patients. CONCLUSION: Remarkable changes in levels of adipokines after bariatric surgery appear like increase in adiponectin and decrease in leptin levels. Significant improvement in anthropometric parameters, metabolic and inflammatory markers occurs, suggesting high potential for reduction of metabolic syndrome and risk for type 2 diabetes. We have shown for the first time ever that level of vitamin D may be involved in resistin regulation.

Total and free vitamin D status among apparently healthy adults living in Duhok Governorate.

Serum total 25-OHD is a main marker of vitamin D which represents the intake and sunlight exposure. Free form of 25-OHD, the small fraction not bound to a transporter protein has been incorporated as a new marker. This cross-sectional study aimed to evaluate the impact of several factors on total and free vitamin D levels in healthy subjects and to find out if the free form of vitamin D could be a better representative of the body's vitamin D status. Total and free 25-OHD were analyzed by ELISA method in a blood sample collected from 391 apparently healthy volunteers (219 female and 172 Male) from Duhok Governorate/Iraq population. Total and free 25-OHD levels were increased proportionally to BMI with lower values seen in the underweight group, also a significant gender differences in total D3 level with higher values in males (23.90 ± 16.41) ng/ml than females (21.24 ± 15.65) ng/ml was observed. Total and Free 25-OHD levels were significantly associated with ages, their deficiency most frequent occurs in the younger ages between (16-25) years old. Smokers had higher level of Total 25-OHD (26.95 ± 19.01) ng/ml and Free 25-OHD (9.47 ± 4.94) pg/ml than nonsmokers (22.14 ± 14.59) ng/ml and (7.87 ± 4.32) pg/ml respectively. A significant increase in Free 25-OHD level in the veiled women (9.12 ± 4.64) ng/ml than unveiled (6.16 ± 3.73) ng/ml with a significant positive correlation between Free 25-OHD level and dress style was also seen. 30% and 33% of the participants whom their daily exposure to sunlight for 30 min and > 1 h respectively were severe deficient in total 25-OHD. 95% of the participants who had Abnormally low level of free D were exposed for ≥ 30 min to sunlight. Daily exposure to sunlight was negatively associated with Free 25-OHD level.

Monthly Increase in Vitamin D Levels upon Supplementation with 2000 IU/Day in Healthy Volunteers: Result from "Integriamoci", a Pilot Pharmacokinetic Study.

Vitamin D (VD) is a calcium- and phosphate-controlling hormone used to treat bone disorders; yet, several other effects are progressively emerging. VD deficiency is highly prevalent worldwide, with suboptimal exposure to sunlight listed among the leading causes: oral supplementation with either cholecalciferol or calcitriol is used. However, there is a scarcity of clinical studies investigating how quickly VD concentrations can increase after supplementation. In this pilot study, the commercial supplement ImmuD3 (by Erboristeria Magentina®) was chosen as the source of VD and 2000 IU/day was administered for one month to 21 healthy volunteers that had not taken any other VD supplements in the previous 30 days. Plasma VD levels were measured through liquid chromatography coupled to tandem mass spectrometry after 7, 14, and 28 days of supplementation. We found that 95% of the participants had insufficient VD levels at baseline (<30 ng/mL; median 23.72 ng/mL; IQR 18.10-26.15), but after 28 days of supplementation, this percentage dropped to 62% (median 28.35 ng/mL; IQR 25.78-35.20). The median increase in VD level was 3.09 ng/mL (IQR 1.60-5.68) after 7 days and 8.85 ng/mL (IQR 2.85-13.97F) after 28 days. This study suggests the need for continuing VD supplementation and for measuring target level attainment.

Multiple vitamin co-exposure and mortality risk: A prospective study.

BACKGROUND & AIMS: Existing epidemiological studies explored the associations of circulating vitamins and mortality focusing on individual vitamin effects, and controversial findings were obtained. The joint effects of multiple vitamin co-exposure are worth studying. The study aimed to elucidate the associations of circulating vitamins and the joint effects of these vitamins' co-exposure with all-cause and cause-specific mortality risks. METHODS: We prospectively evaluated the associations of the concentrations of six kinds of vitamins (A, D, E, C, B12 and B9) in serum with risks for all-cause and cause-specific mortalities among U.S. adults. Mortality status and cause of death were determined by NHANES-linked public available files dated up to 31 December 2015. An unsupervised K-means clustering method was used to cluster the participants into several vitamin co-exposure patterns. The Cox proportional hazards model was used for statistical analysis. RESULTS: A total of 1404 deaths occurred during a median of 10.9 years follow-up among 8295 participants. In multivariable adjustment, increasing levels of vitamin D were associated with reduced all-cause and cause-specific mortality risks. A J-shaped nonlinear exposure-response relationship was observed between all studied vitamins (except for vitamin D) and all-cause mortality risk. Four co-exposure patterns were generated based on the studied vitamins, as follows: low-level exposure (cluster 1), vitamin A/D exposure (cluster 2), water-soluble vitamin exposure (cluster 3) and high-level exposure (cluster 4). Compared with those in cluster 1, participants in cluster 2 had lower all-cause and cancer mortality risks, with hazard ratios (95% confidence intervals [CIs]) of 0.67 (0.53, 0.85) and 0.45 (0.29, 0.71), respectively. CONCLUSIONS: The findings in this study indicated that high circulating vitamin D levels were associated with reduced mortality risk among U.S. adults. Vitamin co-exposure at moderate levels appropriately contributed to low all-cause and cancer mortality risks. Our findings provided a novel perspective for exploring the joint health effects of multivitamin co-exposure. Future investigations are needed to further unravel the underlying mechanisms of possible vitamin interactions.

Vitamin D Status and SARS-CoV-2 Infection in a Cohort of Kidney Transplanted Patients.

BACKGROUND: Recently the protective role of 25-hydroxyvitamin D (25(OH)D) against viral infections has been hypothesized. We evaluated the association between vitamin D status and SARS-CoV-2 infection susceptibility and severity in a cohort of kidney transplanted patients (KTxp). METHODS: A total of 61 KTxp with SARS-CoV-2 infection (COV+) were matched with 122 healthy KTxp controls (COV-). Main biochemical parameters at 1, 6, and 12 months before SARS-CoV-2 infection were recorded. Vitamin D status was considered as the mean of two 25(OH)D measures obtained 6 ± 2 months apart during the last year. The severity of SARS-CoV-2 infection was based on the need for hospitalization (HOSP+) and death (D+). RESULTS: 25(OH)D levels were lower in COV+ than in controls [19(12-26) vs. 23(17-31) ng/mL, p = 0.01]. No differences among the other biochemical parameters were found. The SARS-CoV-2 infection discriminative power of 25(OH)D was evaluated by ROC-curve (AUC 0.61, 95% CI 0.5-0.7, p = 0.01). 25(OH)D was not significantly different between HOSP+ and HOSP- [17(8-25) vs. 20(15-26) ng/mL, p = 0.19] and between D+ and D- [14(6-23) vs. 20(14-26) ng/mL, p = 0.22] and had no significant correlation with disease length. CONCLUSIONS: During the year preceding the infection, 25(OH)D levels were lower in COV+ KTxp in comparison with controls matched for demographic features and comorbidities. No significant association between vitamin D status and SARS-CoV-2 infection related outcomes was found.

Effect of Diet Supplementation with the Mycotoxin Binder Montmorillonite on the Bioavailability of Vitamins in Dairy Cows.

The objective of this study was to determine the effect of the mycotoxin binder montmorillonite (MMT) supplemented in the diet of dairy cows on the bioavailability of vitamins A, D, E, B1 and B6. Six multiparous Holstein-Friesian cows were used in a crossover design with two periods. Treatments were a control diet with or without MMT. Vitamins were infused individually into the abomasum through the ruminal cannula. Blood samples were collected from the jugular vein at 0, 1, 2, 3, 4, 6, 9, 12, 24 and 48 h after the administration of each vitamin. Results showed that vitamin A reached maximal concentration (Tmax) at 5.3 h after dosing, the maximal concentration (Cmax) was 1.2 times higher than the basal concentration (Cbasal), and the area under the curve (AUC) was 739 arbitrary units. Vitamin B6 reached the Tmax at 13 h after dosing, the Cmax was 1.4 times higher than the Cbasal, and the AUC was 222 arbitrary units. No differences were observed in Cbasal, Tmax, Cmax and AUC of vitamin A and B6 between control vs. MMT-supplemented cows. Plasma concentrations of vitamins D, E and B1 had no concentration peaks, and were not affected by MMT addition. The lack of a response suggests that their plasma concentration may be tightly regulated. Results of this study do not show evidence that MMT affects the bioavailability of vitamins A and B6 in vivo.

Staging exocrine pancreatic dysfunction.

Digestive capacity of the gastrointestinal tract, largely but not wholly, depends on exocrine pancreatic function to achieve near complete digestion and absorption of ingested food. Coefficient of fat absorption (CFA), the proportion of ingested fat absorbed (normal >93%), reflects digestive capacity. Exocrine pancreatic insufficiency (EPI) is the state of insufficient digestive capacity (CFA <93%) caused by severe loss of pancreatic exocrine function despite variable compensation by upregulation of extra-pancreatic lipolysis. Fecal elastase 1 (FE1) level is the most widely used, though imperfect, non-invasive test of pancreatic enzyme output. Decline in pancreas enzyme output, or pancreatic exocrine dysfunction (EPD), has a variable correlation with measurable decline in CFA. EPI results in steatorrhea, weight loss and nutrient deficiency, which are mitigated by pancreatic enzyme replacement therapy (PERT). We propose a staging system for EPD, based on measurement of fecal elastase (FE1) and, if necessary, CFA and serum fat-soluble vitamin levels. In Stage I (Mild) EPD, FE1 is 100-200 mcg/gm; if steatorrhea is present, non-pancreatic causes are likely. In Stage II (Moderate) EPD), FE1 is < 100 mcg/gm without clinical and/or laboratory evidence of steatorrhea. In Stage III, there are marked reductions in FE1 and CFA, but vitamin levels remain normal (Severe EPD or EPI without nutritional deficiency). In Stage IV all parameters are abnormal (Severe EPD or EPI with nutritional deficiency). EPD stages I and II are pancreas sufficient and PERT may not be the best or first approach in management of early-stage disease; it needs further study to determine clinical utility. The term EPI refers strictly to EPD Stages III and IV which should be treated with PERT, with Stage IV requiring micronutrient supplementation as well.

Bidirectional Mendelian randomisation analysis of the relationship between circulating vitamin D concentration and colorectal cancer risk.

Epidemiological evidence is consistent with a protective effect of vitamin D against colorectal cancer (CRC), but the observed strong associations are open to confounders and potential reverse causation. Previous Mendelian randomisation (MR) studies were limited by poor genetic instruments and inadequate statistical power. Moreover, whether genetically higher CRC risk can influence vitamin D level, namely the reverse causation, still remains unknown. Herein, we report the first bidirectional MR study. We employed 110 newly identified genetic variants as proxies for vitamin D to obtain unconfounded effect estimates on CRC risk in 26 397 CRC cases and 41 481 controls of European ancestry. To test for reserve causation, we estimated effects of 115 CRC-risk variants on vitamin D level among 417 580 participants from the UK Biobank. The causal association was estimated using the random-effect inverse-variance weighted (IVW) method. We found no significant causal effect of vitamin D on CRC risk [IVW estimate odds ratio: 0.97, 95% confidence interval (CI) = 0.88-1.07, P = .565]. Similarly, no significant reverse causal association was identified between genetically increased CRC risk and vitamin D levels (IVW estimate ß: -0.002, 95% CI = -0.008 to 0.004, P = .543). Stratified analysis by tumour sites did not identify significant causal associations in either direction between vitamin D and colon or rectal cancer. Despite the improved statistical power of this study, we found no evidence of causal association of either direction between circulating vitamin D and CRC risk. Significant associations reported by observational studies may be primarily driven by unidentified confounders.

Genetically predicted circulating vitamin C in relation to cardiovascular disease.

AIM: We conducted a two-sample Mendelian randomization (MR) study to assess the associations of genetically predicted circulating vitamin C levels with cardiovascular diseases (CVDs). METHODS AND RESULTS: Ten lead single-nucleotide polymorphisms associated with plasma vitamin C levels at the genome-wide significance level were used as instrumental variables. Summary-level data for 15 CVDs were obtained from corresponding genetic consortia, the UK Biobank study, and the FinnGen consortium. The inverse-variance-weighted method was the primary analysis method, supplemented by the weighted median and MR-Egger methods. Estimates for each CVD from different sources were combined. Genetically predicted vitamin C levels were not associated with any CVD after accounting for multiple testing. However, there were suggestive associations of higher genetically predicted vitamin C levels (per 1 standard deviation increase) with lower risk of cardioembolic stroke [odds ratio, 0.79; 95% confidence interval (CI), 0.64, 0.99; P = 0.038] and higher risk of atrial fibrillation (odds ratio, 1.09; 95% CI, 1.00, 1.18; P = 0.049) in the inverse-variance-weighted method and with lower risk of peripheral artery disease (odds ratio, 0.76, 95% CI, 0.62, 0.93; P = 0.009) in the weighted median method. CONCLUSION: We found limited evidence with MR techniques for an overall protective role of vitamin C in the primary prevention of CVD. The associations of vitamin C levels with cardioembolic stroke, atrial fibrillation, and peripheral artery disease need further study.

Serum vitamin E levels and chronic inflammatory skin diseases: A systematic review and meta-analysis.

BACKGROUND: Vitamin E has long been linked to skin health, including all of its possible functions in cosmetic products, to its roles in membrane integrity and even the aging process. However, reports on the relationship between serum vitamin E levels and the risk of chronic inflammatory skin diseases have been inconsistent. We performed a systematic review and meta-analysis to evaluate the association between serum vitamin E levels and chronic inflammatory skin diseases. METHODS: We searched the PubMed, Web of Science and Scopus databases, with no time limit up to 30.06.2021. Studies examining serum vitamin E levels in patients with chronic inflammatory skin diseases were selected. RESULTS: Twenty articles met the inclusion criteria. Compared with controls, a lower vitamin E level was found in patients with vitiligo (SMD: -0.70, 95% CI: -1.21 to -0.19), psoriasis (SMD: -2.73, 95% CI: -3.57 to -1.18), atopic dermatitis (SMD: -1.08, 95% CI: -1.80 to -0.36) and acne (SMD: -0.67, 95% CI: -1.05 to -0.30). CONCLUSIONS: Our meta-analysis showed that serum vitamin E levels were lower in patients suffering from vitiligo, psoriasis, atopic dermatitis and acne. This study highlights the need to evaluate vitamin E status to improve its level in patients with skin diseases.

Fat-Soluble Vitamin Supplementation Using Liposomes, Cyclodextrins, or Medium-Chain Triglycerides in Cystic Fibrosis: A Randomized Controlled Trial.

Fat-soluble vitamin deficiency remains a challenge in cystic fibrosis (CF), chronic pancreatitis, and biliary atresia. Liposomes and cyclodextrins can enhance their bioavailability, thus this multi-center randomized placebo-controlled trial compared three-month supplementation of fat-soluble vitamins in the form of liposomes or cyclodextrins to medium-chain triglycerides (MCT) in pancreatic-insufficient CF patients. The daily doses were as follows: 2000 IU of retinyl palmitate, 4000 IU of vitamin D3, 200 IU of RRR-α-tocopherol, and 200 µg of vitamin K2 as menaquinone-7, with vitamin E given in soybean oil instead of liposomes. All participants received 4 mg of ß-carotene and 1.07 mg of vitamin K1 to ensure compliance with the guidelines. The primary outcome was the change from the baseline of all-trans-retinol and 25-hydroxyvitamin D3 concentrations and the percentage of undercarboxylated osteocalcin. Out of 75 randomized patients (n = 28 liposomes, n = 22 cyclodextrins, and n = 25 MCT), 67 completed the trial (89%; n = 26 liposomes, n = 18 cyclodextrins, and n = 23 MCT) and had a median age of 22 years (IQR 19-28), body mass index of 20.6 kg/m2 [18.4-22.0], and forced expiratory volume in 1 s of 65% (44-84%). The liposomal formulation of vitamin A was associated with the improved evolution of serum all-trans-retinol compared to the control (median +1.7 ng/mL (IQR -44.3-86.1) vs. -38.8 ng/mL (-71.2-6.8), p = 0.028). Cyclodextrins enhanced the bioavailability of vitamin D3 (+9.0 ng/mL (1.0-17.0) vs. +3.0 ng/mL (-4.0-7.0), p = 0.012) and vitamin E (+4.34 µg/mL (0.33-6.52) vs. -0.34 µg/mL (-1.71-2.15), p = 0.010). Liposomes may augment the bioavailability of vitamin A and cyclodextrins may strengthen the supplementation of vitamins D3 and E relative to MCT in pancreatic-insufficient CF but further studies are required to assess liposomal vitamin E (German Clinical Trial Register number DRKS00014295, funded from EU and Norsa Pharma).

Insufficient Vitamin C Levels among Adults in the United States: Results from the NHANES Surveys, 2003-2006.

Vitamin C, well-established in immune function and a key factor in epigenetic inflammatory modifications, is only obtained through consistent dietary intake. Identifying individuals at risk for Vitamin C insufficiency may guide prevention and treatment, however, national surveillance has not been evaluated in the United States since 2006. A descriptive, cross-sectional secondary analysis was performed utilizing data from the 2003-2006 National Health and Nutrition Examination Surveys (NHANES) assessing non-institutionalized adults. Five categories of plasma Vitamin C were delineated: deficiency (<11 µmol/L), hypovitaminosis (11-23 µmol/L), inadequate (23-49 µmol/L), adequate (50-69 µmol/L), and saturating (≥70 µmol/L). Results indicated 41.8% of the population possessed insufficient levels (deficiency, hypovitaminosis, and inadequate) of Vitamin C. Males, adults aged 20-59, Black and Mexican Americans, smokers, individuals with increased BMI, middle and high poverty to income ratio and food insecurity were significantly associated with insufficient Vitamin C plasma levels. Plasma Vitamin C levels reveal a large proportion of the population still at risk for inflammatory driven disease with little to no symptoms of Vitamin C hypovitaminosis. Recognition and regulation of the health impact of Vitamin C support the goal of Nutrition and Healthy Eating as part of the Healthy People 2030.

Vitamins as Possible Cancer Biomarkers: Significance and Limitations.

The Western-style diet, which is common in developed countries and spreading into developing countries, is unbalanced in many respects. For instance, micronutrients (vitamins A, B complex, C, D, E, and K plus iron, zinc, selenium, and iodine) are generally depleted in Western food (causing what is known as 'hidden hunger'), whereas some others (such as phosphorus) are added beyond the daily allowance. This imbalance in micronutrients can induce cellular damage that can increase the risk of cancer. Interestingly, there is a large body of evidence suggesting a strong correlation between vitamin intake as well as vitamin blood concentrations with the occurrence of certain types of cancer. The direction of association between the concentration of a given vitamin and cancer risk is tumor specific. The present review summarized the literature regarding vitamins and cancer risk to assess whether these could be used as diagnostic or prognostic markers, thus confirming their potential as biomarkers. Despite many studies that highlight the importance of monitoring vitamin blood or tissue concentrations in cancer patients and demonstrate the link between vitamin intake and cancer risk, there is still an urgent need for more data to assess the effectiveness of vitamins as biomarkers in the context of cancer. Therefore, this review aims to provide a solid basis to support further studies on this promising topic.

Effects of Periodic Religious Fasting for Decades on Nutrient Intakes and the Blood Biochemical Profile.

The aim of the present study was to examine differences and correlations in nutrient intakes and serum parameters related to nutrient intake (lipid profile, vitamins, and trace elements) in 200 lifelong Christian Orthodox Church (COC) fasters with periodic abstinence from certain foods (predominantly of animal origin) for approximately half of the year and 200 non-fasting controls, all of whom did not take dietary supplements. Nutrient intakes were assessed through three-day dietary recalls. Blood samples were drawn for the analysis of potential biomarkers of nutrient intake. Fasters had lower energy intake, due to lower fat and protein intake, compared to non-fasters (p < 0.05). Fasters also had lower intakes of vitamins A, B1, B2, B6, B12, D, folate, pantothenate, sodium, calcium, zinc, and phosphorus. Most participants (in both groups) did not meet the recommended dietary allowances of most vitamins and elements. Most serum biochemical parameters did not reflect the differences in nutrient intakes between groups, and none exhibited a correlation coefficient above 0.5 with nutrient intakes. Our findings suggest that COC fasting is associated with reduced intake of many nutrients, although this does not seem to have an impact on the blood biochemical profile.

Vitamin D Status in Children With Short Stature: Accurate Determination of Serum Vitamin D Components Using High-Performance Liquid Chromatography-Tandem Mass Spectrometry.

Objective: Vitamin D is critical for calcium and bone metabolism. Vitamin D insufficiency impairs skeletal mineralization and bone growth rate during childhood, thus affecting height and health. Vitamin D status in children with short stature is sparsely reported. The purpose of the current study was to investigate various vitamin D components by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) to better explore vitamin D storage of short-stature children in vivo. Methods: Serum circulating levels of 25-hydroxyvitamin D2 [25(OH)D2], 25-hydroxyvitamin D3 [25(OH)D3], and 3-epi-25-hydroxyvitamin D3 [3-epi-25(OH)D3, C3-epi] were accurately computed using the LC-MS/MS method. Total 25(OH)D [t-25(OH)D] and ratios of 25(OH)D2/25(OH)D3 and C3-epi/25(OH)D3 were then respectively calculated. Free 25(OH)D [f-25(OH)D] was also measured. Results: 25(OH)D3 and f-25(OH)D levels in short-stature subgroups 2 (school age: 7~12 years old) and 3 (adolescence: 13~18 years old) were significantly lower compared with those of healthy controls. By contrast, C3-epi levels and C3-epi/25(OH)D3 ratios in all the three short-stature subgroups were markedly higher than the corresponding healthy cases. Based on cutoff values developed by Endocrine Society Recommendation (but not suitable for methods 2 and 3), sufficient storage capacities of vitamin D in short-stature subgroups 1, 2, and 3 were 42.8%, 23.8%, and 9.0% as determined by Method 3 [25(OH)D2/3+25(OH)D3], which were lower than those of 57.1%, 28.6%, and 18.2% as determined by Method 1 [25(OH)D2+25(OH)D3+C3-epi] and 45.7%, 28.5%, and 13.6% as determined by Method 2 [25(OH)D2/3+25(OH)D3+C3-epi]. Levels of 25(OH)D2 were found to be weakly negatively correlated with those of 25(OH)D3, and higher 25(OH)D3 levels were positively correlated with higher levels of C3-epi in both short-stature and healthy control cohorts. Furthermore, f-25(OH)D levels were positively associated with 25(OH)D3 and C3-epi levels in children. Conclusions: The current LC-MS/MS technique can not only separate 25(OH)D2 from 25(OH)D3 but also distinguish C3-epi from 25(OH)D3. Measurement of t-25(OH)D [25(OH)D2+25(OH)D3] alone may overestimate vitamin D storage in children, and short-stature children had lower vitamin D levels compared with healthy subjects. Ratios of C3-epi/25(OH)D3 and 25(OH)D2/25(OH)D3 might be alternative markers for vitamin D catabolism/storage in short-stature children. Further studies are needed to explore the relationships and physiological roles of various vitamin D metabolites.

Association of changes in lipid levels with changes in vitamin D levels in a real-world setting.

In clinical trials, vitamin D supplementation has been reported to reduce serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) but not high-density lipoprotein cholesterol (HDL-C). In this cohort study we evaluated the association between changes in vitamin D (25-hydroxyvitamin D) and changes in lipid levels in a real-world setting. Changes in lipid levels over a 1-year period were evaluated among individuals whose vitamin D levels increased (group 1) or decreased (group 2) by ≥ 10 ng/mL in year 2018 versus 2017 (cohort 1; n = 5580), in 2019 versus 2018 (cohort 2, n = 6057), or in 2020 versus 2019 (cohort 3, n = 7249). In each cohort, levels of TC, LDL-C, and TG decreased in group 1 and increased in group 2. Between-group differences in average changes in the 3 cohorts ranged from 10.71 to 12.02 mg/dL for TC, from 7.42 to 8.95 mg/dL for LDL-C, and from 21.59 to 28.09 mg/dL for TG. These differences were significant after adjusting for age, sex, race, education, body mass index, blood pressure, smoking status, geographical location, and baseline levels of vitamin D and lipids (P < 0.001). Changes in vitamin D levels were not significantly associated with changes in HDL-C levels.