Vitamin C and vitamin E antagonistically modulate human vascular endothelial and smooth muscle cell DNA synthesis and proliferation

Summary Background Vitamin C and E are suggested to play a preventive role in the pathogenesis of atherosclerosis. They reduce oxidation of low density lipoproteins (oxLDL), thereby protecting human vascular arterial endothelial and smooth muscle cells from oxLDL induced damages. Aims of the Study Since vascular arterial endothelial and smooth muscle cells are both involved in atherosclerotic plaque formation, we simultaneously examined the effect of vitamin C, E and oxLDL on their DNA synthesis and proliferation to further elucidate their joint role in this process. Methods Human umbilical arterial endothelial cells (HUAEC) and human arterial smooth muscle cells (HUASMC) were incubated with “preventive concentrations” of vitamin C (60μM) and E (30μM) and with LDL (60μg/ml) of increasing oxidation grade. Cell proliferation and DNA synthesis were determined by cell count and [³H]-thymidine uptake, respectively. Results Vitamin C alone or in combination with E increased significantly cell number and [³H]-thymidine uptake in HUAEC. The combination exhibited the strongest effect. In contrast, cell number and [³H]-thymidine uptake in HUASMC were significantly decreased in the presence of vitamin C, vitamin E or its combination. OxLDL (60 μg/ml) inhibited cell number and [³H]-thymidine uptake in HUAECs, the latter in an oxidation-grade dependent manner. In HUASMC oxLDL promoted a higher cell number and [³H]-thymidine uptake. If induced by minimally oxLDL, this reduc-tion or increase could be partially reversed by vitamin C alone or in combination with vitamin E. Conclusion Vitamin C and E, alone or in combination, modulate proliferation and DNA synthesis of human arterial endothelial and muscle cells and this modulation is antagonistic. Thus, vitamin C and E may act “preventive” on atherosclerotic plaque formation in two steps: first reendothelialisation is promoted, then HUASMC growth is inhibited. Received: 23 August 2001, Accepted: 8 January 2002     

Comparison of dosimetry between PET/CT and PET alone using <Superscript>11</Superscript>C-ITMM

We used a new tracer, N-[4-[6-(isopropylamino) pyrimidin-4-yl]-1,3-thiazol-2-yl]-4-¹¹C-methoxy-N-methylbenzamide (¹¹C-ITMM), to compare radiation doses from positron emission tomography (PET)/computed tomography (CT) with previously published doses from PET alone. Twelve healthy volunteers [six males (mean age ± SD, 27.7 ± 6.7 years) and six females (31.8 ± 14.5 years)] in 12 examinations were recruited. Dose estimations from PET/CT were compared with those from PET alone. Regions of interest (ROIs) in PET/CT were delineated on the basis of low-dose CT (LD-CT) images acquired during PET/CT. Internal and external radiation doses were estimated using OLINDA/EXM 1.0 and CT-Expo software. The effective dose (ED) for ¹¹C-ITMM calculated from PET/CT was estimated to be 4.7 ± 0.5 μSv/MBq for the male subjects and 4.1 ± 0.7 μSv/MBq for the female subjects. The mean ED for ¹¹C-ITMM calculated from PET alone in a previous report was estimated to be 4.6 ± 0.3 μSv/MBq (males, n = 3). The ED values for ¹¹C-ITMM calculated from PET/CT in the male subjects were almost identical to those from PET alone. The absorbed doses (ADs) of the gallbladder, stomach, red bone marrow, and spleen calculated from PET/CT were significantly different from those calculated from PET alone. The EDs of ¹¹C-ITMM calculated from PET/CT were almost identical to those calculated from PET alone. The ADs in several organs calculated from PET/CT differed from those from PET alone. LD-CT images acquired during PET/CT may facilitate organ identification.     

Vitamin C Supplementation Slightly Improves Physical Activity Levels and Reduces Cold Incidence in Men with Marginal Vitamin C Status: A Randomized Controlled Trial

The early indications of vitamin C deficiency are unremarkable (fatigue, malaise, depression) and may manifest as a reduced desire to be physically active; moreover, hypovitaminosis C may be associated with increased cold duration and severity. This study examined the impact of vitamin C on physical activity and respiratory tract infections during the peak of the cold season. Healthy non-smoking adult men (18–35 years; BMI < 34 kg/m²; plasma vitamin C < 45 µmol/L) received either 1000 mg of vitamin C daily (n = 15) or placebo (n = 13) in a randomized, double-blind, eight-week trial. All participants completed the Wisconsin Upper Respiratory Symptom Survey-21 daily and the Godin Leisure-Time Exercise Questionnaire weekly. In the final two weeks of the trial, the physical activity score rose modestly for the vitamin C group vs. placebo after adjusting for baseline values: +39.6% (95% CI [−4.5,83.7]; p = 0.10). The number of participants reporting cold episodes was 7 and 11 for the vitamin C and placebo groups respectively during the eight-week trial (RR = 0.55; 95% CI [0.33,0.94]; p = 0.04) and cold duration was reduced 59% in the vitamin C versus placebo groups (−3.2 days; 95% CI [−7.0,0.6]; p = 0.06). These data suggest measurable health advantages associated with vitamin C supplementation in a population with adequate-to-low vitamin C status.     

Perinatal influences on the uptake of newborn Vitamin K prophylaxis – a retrospective cohort study

Objectives: To describe rates of newborn vitamin K prophylaxis uptake according to method of administration (intramuscular [IM], oral, refused) and identify predictors for the choice of oral administration and for refusal of vitamin K prophylaxis. Methods: A retrospective cohort study examined the relationship between method of vitamin K administration and various exposure factors (infant, maternal, socio‐demographic and healthcare professional). Written and electronic data for births from a single tertiary birthing unit in New Zealand (NZ) were examined over a four‐year period from January 2009 to December 2012. Results: Records for 7,089 mothers/babies were examined. Of these, 92.9% of infants received IM and 5.4% oral vitamin K. Refusal of vitamin K was associated with (OR [95%CI]): Asian ethnicity (5.87 [3.61 to 9.53] p<0.001); vaginal delivery (2.85 [1.83 to 4.43] p<0.001); and gestational age, per additional week, (1.24 [1.10 to 1.39) p<0.001). Oral vitamin K was associated with (OR [95%CI]): Asian ethnicity (2.61 [1.80 to 3.79] p<0.001); obstetric nurse as the Lead Maternity Carer (LMC) (2.65 [1.73 to 4.06] p<0.001); vaginal delivery (2.34 [1.84 to 2.96] p<0.001); gestational age, per week, (1.14 [1.07 to 1.21] p<0.001); and LMC experience, per decade (0.61 [0.51 to 0.74] p<0.001). Conclusions: This study reveals several important and novel associations with mode of administration of newborn vitamin K prophylaxis. IM vitamin K uptake was also lower than international data, largely due to increased oral uptake. Implications: Uptake of vitamin K is associated with ethnicity and also factors in the infant that might imply a perceived protection against vitamin K deficiency bleeding. Further investigation is required for a fuller understanding of the motivations for choosing differing routes of vitamin K administration in newborns, with particular emphasis on factors influencing parental choice.     

The diagnostic value of [18F]-FDG-PET/CT in hematopoietic radiation toxicity: a Tibet minipig model

This study was undertaken to assess the diagnostic value of 2-[¹⁸F]-fluoro-2-deoxy-D-glucose positron emission tomography with computed tomography ([¹⁸F]-FDG-PET/CT) in the detection of radiation toxicity in normal bone marrow using Tibet minipigs as a model. Eighteen Tibet minipigs were caged in aseptic rooms and randomly divided into six groups. Five groups (n = 3/group) were irradiated with single doses of 2, 5, 8, 11 and 14 Gy of total body irradiation (TBI) using an 8-MV X-ray linear accelerator. These pigs were evaluated with [¹⁸F]-FDG-PET/CT, and their marrow nucleated cells were counted. The data were initially collected at 6, 24 and 72 h after treatment and were then collected on Days 5–60 post-TBI at 5-day intervals. At 24 and 72 h post-TBI, marrow standardized uptake value (SUV) data showed a dose-dependent decrease in the radiation dose range from 2–8 Gy. Upon long-term observation, SUV and marrow nucleated cell number in the 11-Gy and 14-Gy groups showed a continuous and marked reduction throughout the entire time course, while Kaplan–Meier curves of survival showed low survival. In contrast, the SUVs in the 2-, 5- and 8-Gy groups showed early transient increases followed by a decline from approximately 72 h through Days 5–15 and then normalized or maintained low levels through the endpoint; marrow nucleated cell number and survival curves showed approximately the same trend and higher survival, respectively. Our findings suggest that [¹⁸F]-FDG-PET/CT may be helpful in quickly assessing the absorbed doses and predicting the prognosis in patients.     

维生素E、维生素C在肥胖儿童中抗氧化作用的临床研究

目的：探讨VitE与VitC在肥胖儿中的抗氧化作用。方法：检测62例肥胖儿童服用VitE和VitC前后血浆VitE、VitC、红细胞超氧化物歧化酶（SOD）活性及过氧化脂质（LPO）水平，与对照组进行比较。结果：在肥胖儿童组，除LPO值明显高于对照组外（P＜0．01），血浆VitE和VitC及红细胞SOD值均低于对照组（P＜0．05），服药后VitE和VitC血浆含量未发生明显变化（P＞0．05），而SOD值高于服药前，LPO降低（P＜0．05）。结论：肥胖儿童患者可能存在抗氧化机能降低现象。     

Vitamin D Deficiency in Pregnant Ukrainian Women: Effects of Alcohol Consumption on Vitamin D Status

Objective: Heavy alcohol consumption can alter vitamin D status; however, the relationships between alcohol consumption and vitamin D concentrations in pregnant women have not been well studied. The aim of this study was to investigate the vitamin D status in a population of alcohol-exposed (N = 180) and low/unexposed control (N = 179) Ukrainian pregnant women.

Methods: Women who attended prenatal care facilities in 2 regions of Ukraine (Rivne and Khmelnytsky) for a routine prenatal visit were screened for the study. At the time of enrollment (20.4 ± 7.0 weeks of gestation), blood samples and alcohol consumption data (during a typical week around conception and the most recent 2 weeks) were collected. Vitamin D status was assessed by 25-hydroxyvitamin D [25(OH)D] concentrations.

Results: A high prevalence of suboptimal vitamin D status in pregnant Ukrainian women was observed. Overall, 50.1% and 33.4% of the women were classified as vitamin D deficient [25(OH)D < 20 ng/mL] or insufficient [25(OH)D ≥ 20 ng/mL and ≤30 ng/mL], respectively, based on 2011 Endocrine Society guidelines. Alcohol-exposed women had significantly lower 25(OH)D concentrations than low/unexposed women in Spring (p = 0.006) and Winter (p = 0.022). When vitamin D concentrations were grouped into sunny season (Summer + Fall) compared to not sunny season (Winter + Spring), there was a significant ethanol by season interaction (p = 0.0028), with alcohol-drinking women having lower circulating vitamin D compared to low/unexposed women in seasons of low sun availability.

Conclusions: These data suggest that when vitamin D concentrations are generally low (e.g., during seasons of low sun availability), alcohol consumption during pregnancy has a negative impact on vitamin D status.     

Pharmacokinetics of High-Dose Weekly Oral Vitamin D3 Supplementation during the Third Trimester of Pregnancy in Dhaka,Bangladesh

A pharmacokinetic study was conducted to assess the biochemical dose-response and tolerability of high-dose prenatal vitamin D3 supplementation in Dhaka, Bangladesh (23°N). Pregnant women at 27–30 weeks gestation (n = 28) were randomized to 70,000 IU once + 35,000 IU/week vitamin D3 (group PH: pregnant, higher dose) or 14,000 IU/week vitamin D3 (PL: pregnant, lower dose) until delivery. A group of non-pregnant women (n = 16) was similarly administered 70,000 IU once + 35,000 IU/week for 10 weeks (NH: non-pregnant, higher-dose). Rise (∆) in serum 25-hydroxyvitamin D concentration ([25(OH)D]) above baseline was the primary pharmacokinetic outcome. Baseline mean [25(OH)D] were similar in PH and PL (35 nmol/L vs. 31 nmol/L, p = 0.34). A dose-response effect was observed: ∆[25(OH)D] at modeled steady-state was 19 nmol/L (95% CI, 1 to 37) higher in PH vs. PL (p = 0.044). ∆[25(OH)D] at modeled steady-state was lower in PH versus NH but the difference was not significant (−15 nmol/L, 95% CI −34 to 5; p = 0.13). In PH, 100% attained [25(OH)D] ≥ 50 nmol/L and 90% attained [25(OH)D] ≥ 80 nmol/L; in PL, 89% attained [25(OH)D] ≥ 50 nmol/L but 56% attained [25(OH)D] ≥ 80 nmol/L. Cord [25(OH)D] (n = 23) was slightly higher in PH versus PL (117 nmol/L vs. 98 nmol/L; p = 0.07). Vitamin D3 was well tolerated; there were no supplement-related serious adverse clinical events or hypercalcemia. In summary, a regimen of an initial dose of 70,000 IU and 35,000 IU/week vitamin D3 in the third trimester of pregnancy was non-hypercalcemic and attained [25(OH)D] ≥ 80 nmol/L in virtually all mothers and newborns. Further research is required to establish the safety of high-dose vitamin D3 in pregnancy and to determine if supplement-induced [25(OH)D] elevations lead to maternal-infant health benefits.     

Increased Plasma Concentrations of Vitamin D Metabolites and Vitamin D Binding Protein in Women Using Hormonal Contraceptives: A Cross-Sectional Study

Use of hormonal contraceptives (HC) may influence total plasma concentrations of vitamin D metabolites. A likely cause is an increased synthesis of vitamin D binding protein (VDBP). Discrepant results are reported on whether the use of HC affects free concentrations of vitamin D metabolites. Aim: In a cross-sectional study, plasma concentrations of vitamin D metabolites, VDBP, and the calculated free vitamin D index in users and non-users of HC were compared and markers of calcium and bone metabolism investigated. Results: 75 Caucasian women aged 25–35 years were included during winter season. Compared with non-users (n = 23), users of HC (n = 52) had significantly higher plasma concentrations of 25-hydroxyvitamin D (25OHD) (median 84 interquartile range: [67-111] vs. 70 [47-83] nmol/L, p = 0.01), 1,25-dihydroxyvitamin D (1,25(OH)₂D) (198 [163-241] vs. 158 [123-183] pmol/L, p = 0.01) and VDBP (358 [260-432] vs. 271 [179-302] µg/mL, p < 0.001). However, the calculated free indices (FI-25OHD and FI-1,25(OH)₂D) were not significantly different between groups (p > 0.10). There were no significant differences in indices of calcium homeostasis (plasma concentrations of calcium, parathyroid hormone, and calcitonin, p > 0.21) or bone metabolism (plasma bone specific alkaline phosphatase, osteocalcin, and urinary NTX/creatinine ratio) between groups. In conclusion: Use of HC is associated with 13%–25% higher concentrations of total vitamin D metabolites and VDBP. This however is not reflected in indices of calcium or bone metabolism. Use of HC should be considered in the interpretation of plasma concentrations vitamin D metabolites.     

The Effect of Vitamin A Supplementation on Thyroid Function in Premenopausal Women

Objective: Vitamin A and its retinoid derivates play an important role in regulation of normal growth and development. Vitamin A has been shown to regulate thyroid hormone metabolism and inhibit thyroid-stimulating hormone (TSH) secretion via down regulation of TSH-β gene expression; however, the effect of vitamin A on thyroid function in obese individuals who are at higher risk of subclinical hypothyroidism is still unclear. In the present study we investigate the impact of vitamin A supplementation on thyroid function in obese women.

Method: A 4-month randomized, double blind controlled trial was conducted among 84 healthy women aged 17–50 years old: 56 were obese (body mass index [BMI] 30–35 kg/m²) and 28 were nonobese (BMI 18.5–24.9 kg/m²). Obese women were randomly allocated to receive either vitamin A (25,000 IU/d retinyl palmitate) or placebo. Nonobese women received vitamin A. At baseline and 4 months after intervention, serum concentrations of TSH, total thyroxine (T4), total triiodothyronine (T3), retinol-binding protein (RBP), and transthyretin (TTR) were measured.

Results: Baseline concentrations of thyroid hormones, RBP and TTR were not significantly different between groups. Vitamin A caused a significant reduction in serum TSH concentrations in obese (p = 0.004) and nonobese (p = 0.001) groups. Serum T3 concentrations also increased in both obese and nonobese vitamin A–treated groups (p < 0.001). Serum T4 decreased in all 3 groups after treatment. The results showed a significant reduction in serum RBP in the obese group after vitamin A supplementation (p = 0.007), but no significant change was seen in serum TTR.

Conclusions: Serum TSH concentrations in vitamin A–treated subjects were significantly reduced; therefore, vitamin A supplementation might reduce the risk of subclinical hypothyroidism in premenopausal women.     

A Significant Positive Association of Vitamin D Deficiency with Coronary Artery Calcification among Middle-aged Men: For the ERA JUMP Study

Objective: Although a significant positive association of vitamin D deficiency with coronary heart disease has been demonstrated in cross-sectional as well as prospective studies, only a few studies have examined the association of vitamin D deficiency with subclinical atherosclerosis. We examined whether vitamin D deficiency is associated with subclinical atherosclerosis, as measured by coronary artery calcification (CAC) in asymptomatic adults.

Methods: In a population-based cross-sectional study, 195 men aged 40 to 49 years without cardiovascular disease were randomly selected (98 Caucasian and 97 Japanese American men). Liquid chromatography–tandem mass spectrometry was utilized to measure serum vitamin D. CAC was examined by electron beam computed tomography using standardized protocols and read centrally at the University of Pittsburgh using Agatston's methods. To investigate an association between vitamin D deficiency (defined as 25-hydroxyvitamin D [25(OH)D] < 20 ng/mL) and CAC (defined as Agatston score ≥ 10), we utilized multivariable logistic regression models.

Results: Prevalence of CAC and vitamin D deficiency was 27.2% and 10.3%, respectively. Participants with CAC were significantly older, had significantly higher body mass index (BMI), and had higher rates of smoking. Those with CAC were 3.31 times likely to be vitamin D deficient, after adjusting for traditional cardiovascular risk factors (odds ratio [OR] = 3.31, 95% confidence interval [CI], 1.12–9.77).

Conclusions: In this population-based study of healthy middle-aged men, vitamin D deficiency had a significant positive association with the presence of CAC.     

The Influence of Smoking on Vitamin C Status During the Third Trimester of Pregnancy and on Vitamin C Levels in Maternal Milk

Objective: The aim of the present investigation was to determine the differences in vitamin C status of 57 Spanish women smokers (S) and nonsmokers (N) in their third trimester of pregnancy, and the concentrations of vitamin C in their milk.

Methods: Vitamin C intake during the third trimester was determined by recording the consumption of foods over a 5-day period (including a Sunday) and by registering vitamin C provided by dietary supplements. Vitamin C levels in maternal serum during this stage of pregnancy and in transition (days 13 to 14 of lactation) and mature milk (day 40 of lactation) were determined colorimetrically. Subjects also answered a questionnaire on their smoking habits during pregnancy.

Results: S subjects (n=16) showed a lower intake of fruits, vegetables and vitamin C than did N subjects (n=41), though these differences were not significant (17.1% of N subjects and 31.2% of S subjects took less than 80 mg of vitamin C per day). Neither were any differences found between the two groups in serum vitamin C levels. However, N subjects showed significantly greater vitamin C levels in both transition and mature milk (431.6±296.5 μmol/L and 496.1±325.6 μmol/L, respectively for N subjects, and 233.7±202.9 μmol/L and 241.3±293.1 μmol/L for S subjects). Further investigations are necessary to determine the clinical consequences of these observations, though it is already known that maternal smoking favors peroxidation events in newborn infants.

Conclusions: If the concentration of antioxidants (vitamin C) in smokers’ breast milk is also lower, this might aggravate the peroxidation problems of their newborn.     

Prevalence of Undernutrition and Vitamin A Deficiency in the Dogon Region,Mali

Objectives: A representative sample of 1510 preschool children living in the Bandiagra circle (Mopti Region, Mali) was examined between March and April 1997 to determine the level of vitamin A deficiency.

Methods: Using a randomized two level cluster sampling, 20 clusters of 75 children aged six months to six years were selected for evaluating xerophthalmia (XN night blindness and/or X1B Bitot spot). Concurrently stature and weight were determined. A semiquantitative seven-day dietary questionnaire was applied to the mothers of 484 infants to assess consumption of vitamin A rich foodstuffs. The prevalence of biochemical deficiency was attested using the Modified Relative Dose Response test (MRDR) on a sub-sample of 192.

Results: Of the studied children, 4.3% (95% Confidence interval [CI]: 3.2–5.3) reported night blindness and 2% (95% CI: 1.3–2.7) had Bitot spots. Prevalence of xerophthalmia attested by at least one of these signs was 5.4% (95% CI: 4.2–6.5). The prevalence reached 10.5% at three years of age. The MRDR test proved abnormal in 77.1% of the subjects (95% CI: 70.3–82.7). Serum retinol was lower than 0.35 μmol/L in 43.8% (95.6% CI: 36.9–51.3) and less than 0.70 μmol/L in 92.7% of the children (95% CI: 87.8–95.8). Weekly consumption of vitamin A rich food was rare: 75.8% had not eaten any animal vitamin A rich food, and 22.1% had consumed less than seven times a vitamin A rich food of either vegetable or animal origin.

Conclusions: These data define vitamin A deficiency as a severe public health problem in the Bandiagara area of Mali.     

Effect of Five-Year Supplementation of Vitamin C on Serum Vitamin C Concentration and Consumption of Vegetables and Fruits in Middle-Aged Japanese: A Randomized Controlled Trial

Objective: This study was aimed at evaluating the effect of long-term vitamin C supplementation on serum and dietary vitamin C and identifying the factors associated with change in serum concentration.

Methods: A total of 439 subjects with atrophic gastritis initially participated in a randomized clinical trial using vitamin C and β-carotene to prevent gastric cancer. We originally randomized the participants into four treatment groups using a 2×2 factorial design, whereby 0 or 15 mg/day β-carotene and 50 or 500 mg/day vitamin C were administered in a double-blind manner. The β-carotene component was terminated early after a mean treatment duration of four months. Before and upon early termination of β-carotene supplementation, 134 subjects dropped out this trial, while 120 and 124 subjects took the vitamin C supplement at either 50 mg or 500 mg daily for five years.

Results: Changes in serum vitamin C were significantly higher in the high-dose group (38.5% increase, 95% CI = 27.0–49.9) than in the low-dose group (13.0% increase, 5.1–20.9) or in the dropout group (3.3% increase, ?2.1–8.6) after five-year supplementation. The serum vitamin C at baseline was negatively associated with changes in serum vitamin C (p < 0.0001), while high-dose (p < 0.0001) and low-dose (p < 0.05) supplementation and female gender (p < 0.001) were positively associated. Dietary intake of vitamin C in the supplementation group was almost identical before and after five-year supplementation of vitamin C (2.31 mg/day decrease, 95% CI = ?15.3–10.7), while a 17.7 mg/day decrease (95% CI = ?44.2–8.86) was observed in the drop-out group.

Conclusion: Five-year vitamin C supplementation induces a remarkable increase in serum vitamin C concentration, and our intervention program appears to have no effect on dietary vitamin C intake.     

Serum vitamin D level is negatively associated with carotid atherosclerosis in Korean adults

The present study investigated the associations between serum vitamin D levels and carotid intima-media thickness (CIMT), carotid plaque and atherosclerosis in 71 Korean adults. CIMT and the presence of carotid plaque were assessed with a high-resolution B-mode ultrasound system, and carotid atherosclerosis was defined as a mean CIMT value >0.9?mm or the presence of carotid plaque. A vitamin D deficiency was associated with the presence of carotid plaque (adjusted odds ratio [aOR]: 9.25, 95% confidence interval [CI]: 1.52–56.3; p?=?0.016). As serum vitamin D levels increased, the presence of high-risk carotid plaque decreased (aOR: 0.84, 95%CI: 0.72–0.99; p?=?0.039). Serum vitamin D levels was negatively associated with carotid atherosclerosis (aOR: 0.86, 95%CI: 0.76–0.97; p?=?0.018). Further studies are needed to investigate whether vitamin D supplementation would be effective for the prevention of atherosclerosis and cardiovascular diseases.     

Effect of Concomitant Consumption of Fish Oil and Vitamin E on T Cell Mediated Function in the Elderly: A Randomized Double-Blind Trial

Objectives: To determine if concomitant consumption of fish oil and vitamin E would modify the vitamin E level needed for improving T cell mediated function in elderly.

Methods: A randomized and double-blind study was conducted using 40 healthy male and female elderly subjects (>65 y) who were randomly assigned to one of 4 groups (n = 10/group). All the subjects received 5 g of fish oil daily containing 1.5 g eicosapentaenoic acid (EPA) and 1 g docosahexaenoic acid (DHA), and a capsule containing different doses of dl-α-tocopherol (0, 100, 200 or 400 mg/day) for 3 mo. Plasma vitamin E and fatty acid levels, and in vivo [delayed-type hypersensitivity skin response (DTH) and T cell sub-population analysis] and ex vivo [mitogen-stimulated peripheral blood mononuclear cells (PBMC) proliferation and interleukin (IL)-2 production] immune functions were determined at baseline and after supplementation.

Results: The control group (fish oil only) did not show a statistically significant change in either DTH or PBMC proliferation. DTH response, however, was significantly increased from baseline in all groups supplemented with fish oil plus vitamin E and a significant positive correlation between DTH response and plasma concentrations of α-tocopherol was observed. PBMC proliferation was only significantly increased in the group supplemented with fish oil plus 200 mg vitamin E. However, the changes caused by fish oil plus vitamin E in either DTH or PBMC proliferation were not significantly different from those observed in control group. Plasma levels of α-tocopherol were significantly increased in all three fish oil plus vitamin E groups and the increase in plasma α-tocopherol level was less profound than that previously reported when vitamin E was given alone.

Conclusions: The immuno-enhancing effect of vitamin E in the elderly is dampened when it is concomitantly consumed with fish oil. This may be due to the smaller increase in plasma concentrations of vitamin E in the presence of fish oil.     

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 β-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).     

Vitamin D Status and Risk of Cystic Fibrosis-Related Diabetes: A Retrospective Single Center Cohort Study

Objective: Cystic fibrosis-related diabetes (CFRD) affects up to half of the people with cystic fibrosis (CF) by adulthood. CFRD is primarily caused by pancreatic dysfunction that leads to insufficient insulin release and/or insulin resistance. Exocrine pancreatic insufficiency in people with CF is associated with fat-soluble vitamin malabsorption, including vitamins A, D, E, and K. This study examined the relationship between vitamin D status, assessed by serum 25-hydroxyvitamin D (25(OH)D), and the development of CF-related diabetes (CFRD) in adults with CF. Methods: This was a retrospective cohort study of adults seen at a single CF center. The data were extracted from the electronic medical records and the Emory Clinical Data Warehouse, a data repository of health information from patients seen at Emory Healthcare. We collected age, race, the first recorded serum 25-hydroxyvitamin D (25(OH)D) concentration, body mass index (BMI), and onset of diabetes diagnosis. Log-rank (Mantel–Cox) tests were used to compare the relative risk of CFRD onset in the subjects with stratified vitamin D status and weight status. A sub-group analysis using chi-square tests assessed the independence between vitamin D deficiency and CFRD risk factors, including gender and CF mutation types (homozygous or heterozygous for F508del, or others). Unpaired t-tests were also used to compare the BMI values and serum 25(OH)D between the CF adults based on the CFRD development. Results: This study included 253 subjects with a mean age of 27.1 years (±9.0), a mean follow-up time period of 1917.1 (±1394.5) days, and a mean serum 25(OH)D concentration of 31.8 ng/mL (±14.0). The majority (52.6%) of the subjects developed CFRD during the study period. Vitamin D deficiency (defined as 25(OH)D < 20 ng/mL) was present in 25.3% of the subjects. Close to two thirds (64.1%) of the subjects with vitamin D deficiency developed CFRD during the study. Vitamin D deficiency increased the risk of developing CFRD (chi-square, p = 0.03) during the course of the study. The time to the onset of CFRD stratified by vitamin D status was also significant (25(OH)D < 20 ng/mL vs. 25(OH)D ≥ 20 ng/mL) (95% CI: 1.2, 2.7, p < 0.0078). Conclusion: Our findings support the hypothesis that adults with CF and vitamin D deficiency are at a higher risk of developing CFRD and are at risk for earlier CFRD onset. The maintenance of a serum 25(OH)D concentration above 20 ng/mL may decrease the risk of progression to CFRD.     

Association between Vitamin D Receptor Polymorphism and Serum Vitamin D Levels in Children with Low-Energy Fractures

Objective: Fractures of bones, especially forearm fractures, are very common in children and their number is increasing. This study was designed to determine the impact of vitamin D serum levels and vitamin D receptor (VDR) polymorphisms on the occurrence of low-energy fractures in children.

Methods: The study group consisted of 100 children with clinically relevant bone fractures and a control group consisted of 127 children without fractures. Total vitamin D [25(OH)D3 plus 25(OH)D2] serum concentrations were evaluated in every patient. Genotypes for 4 restriction fragment length polymorphisms of the vitamin D receptor gene (FokI, ApaI, TaqI, and BsmI) were determined by standard polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) techniques.

Results: Differences in concentrations of vitamin D were observed between the group with bone fractures (median = 12 ng/ml) and the control group (median = 16 ng/ml; p = 0.000044).

Higher levels of vitamin D reduced the risk of fracture by 1.06 times (p = 0.0005). No impact of particular VDR polymorphism on the occurrence of low-energy fractures in children was detected. However, there were significant differences in the prevalence of FokI polymorphism genotypes between the fracture and control groups (p = 0.05). Furthermore, the recessive “aa” genotype of ApaI polymorphism and the dominant “TT” genotype of TaqI polymorphism were associated with higher levels of vitamin D (p = 0.005 and p = 0.036, respectively).

Conclusions: Vitamin D deficiency is an independent risk factor for fractures in children. ApaI polymorphism recessive “aa” and TaqI polymorphism dominant “TT” genotypes are associated with higher levels of vitamin D in serum.     

Vitamin D status and resistance exercise training independently affect glucose tolerance in older adults

We assessed the influence of serum 25-hydroxyvitamin D (25[OH]D) and parathyroid hormone (PTH) concentrations on oral glucose tolerance, body composition, and muscle strength in older, nondiabetic adults who performed resistance exercise training (RT) while consuming diets with either 0.9 or 1.2 g protein kg⁻¹ d⁻¹. We hypothesized that individuals with insufficient 25(OH)D and/or high PTH would have less improvement in glucose tolerance after 12 weeks of RT compared with individuals with sufficient 25(OH)D and lower PTH. Sixteen men and 19 women (aged 61 ± 8 years; range, 50-80 years; body mass index, 26.3 ± 3.6 kg/m²) performed RT 3 times/wk for 12 weeks, with oral glucose tolerance tests done at baseline and postintervention. Protein intake did not influence the responses described below. Plasma glucose area under the curve (P = .02) and 2-hour plasma glucose concentration (P = .03) were higher for vitamin D–insufficient subjects (25[OH]D <50 nmol/L, n = 7) vs vitamin D–sufficient subjects (25[OH]D ≥50 nmol/L, n = 28). These differences remained significant after adjustment for age and body mass index. Resistance exercise training reduced fat mass (mean ± SD, −6% ± 7%; P < .001) and increased lean body mass (2% ± 3%, P < .001) and whole-body muscle strength (32% ± 17%, P < .001) in these weight-stable subjects but did not affect 25(OH)D or PTH concentrations. Oral glucose tolerance improved after RT (−10% ± 16% in glucose area under the curve and −21% ± 40% in 2-hour glucose, P = .001), but baseline 25(OH)D and PTH did not influence these RT-induced changes. These findings indicate that vitamin D status and RT independently affect glucose tolerance, and a training-induced improvement in glucose tolerance does not offset the negative effect of insufficient vitamin D status in older, nondiabetic adults.