Effect of Calcifediol on Physical Performance and Muscle Strength Parameters: A Systematic Review and Meta-Analysis

There is general agreement that optimal vitamin D status is necessary for bones, muscles, and general health, particularly in older adults, who are at higher risk of negative consequences of vitamin D deficiency, including sarcopenia; vitamin D supplementation is proposed as a potential intervention to mitigate sarcopenia. Several RCTs have reported that calcifediol (25(OH)D) was more potent than cholecalciferol in increasing plasma 25(OH)D. The present systematic review and meta-analysis aimed to summarize the effects of calcifediol on physical performance and muscle strength. We searched databases from inception to 1 January 2022 for studies investigating calcifediol on physical performance or muscle strength parameters. We calculated the difference between the means of follow-up vs. baseline data using standardized mean differences (SMD) and their 95% confidence intervals (CIs); a random-effect model was considered for all of the analyses. Seven RCTs were included in the meta-analysis. Calcifediol significantly improved gait speed (SMD = 2.500; 95%CI = 1.768–3.223; p < 0.0001); handgrip strength (n = 5446 participants, SMD = 0.532; 95%CI: 0.305–0.758; p < 0.0001; I² = 20.2%); and leg extension (n = 4318 participants, SMD = 0.641; 95%CI: 0.346 to 0.935; p < 0.0001; I² = 18.8%;) vs. baseline values. In conclusion, in this systematic review and meta-analysis, we observed that calcifediol may have a positive effect on muscle strength parameters, with less evidence on physical performance. These data further indicate the importance of vitamin D and, in particular, of calcifediol, not only on bone metabolism but also on muscle parameters and sarcopenia.     

Leucine Supplementation Accelerates Connective Tissue Repair of Injured Tibialis Anterior Muscle

This study investigated the effect of leucine supplementation on the skeletal muscle regenerative process, focusing on the remodeling of connective tissue of the fast twitch muscle tibialis anterior (TA). Young male Wistar rats were supplemented with leucine (1.35 g/kg per day); then, TA muscles from the left hind limb were cryolesioned and examined after 10 days. Although leucine supplementation induced increased protein synthesis, it was not sufficient to promote an increase in the cross-sectional area (CSA) of regenerating myofibers (p > 0.05) from TA muscles. However, leucine supplementation reduced the amount of collagen and the activation of phosphorylated transforming growth factor-β receptor type I (TβR-I) and Smad2/3 in regenerating muscles (p < 0.05). Leucine also reduced neonatal myosin heavy chain (MyHC-n) (p < 0.05), increased adult MyHC-II expression (p < 0.05) and prevented the decrease in maximum tetanic strength in regenerating TA muscles (p < 0.05). Our results suggest that leucine supplementation accelerates connective tissue repair and consequent function of regenerating TA through the attenuation of TβR-I and Smad2/3 activation. Therefore, future studies are warranted to investigate leucine supplementation as a nutritional strategy to prevent or attenuate muscle fibrosis in patients with several muscle diseases.     

Correlation between Levels of Vitamins D3 and E in Type 2 Diabetes Mellitus: A Case-Control Study in Serdang,Selangor, Malaysia

An overview of vitamins D₃ and E suggests micronutrient deficiency contributes to type 2 diabetes mellitus (T2DM). A case-control study was conducted to determine the status of plasma vitamins D₃ and E isomers amongst diabetic Malaysians. Two groups were recruited for participation, one comprising fifty diabetic subjects (DM) and one comprising fifty non-diabetic (non-DM) subjects, in order to assess their plasma vitamin D₃, calcium and vitamin E status. Glycaemic status (haemoglobin A1c, HbA1c; fasting blood glucose, FBG; C-Peptide) and lipid profiles (total cholesterol, TC; triglycerides, TG; low-density lipoprotein-cholesterol, LDL-C; high-density lipoprotein-cholesterol, HDL-C) were assessed, followed by anthropometric measurements. The Mann–Whitney U-test, Kruskal–Wallis and Spearman’s correlation coefficient were used to elucidate the association between levels of plasma vitamins D₃ and E and T2DM. The vitamin D₃ deficiency group (<20 ng/mL) showed a significant correlation (p < 0.05) with glycaemic status (HbA1c and FBG) and lipid profiles (HDL-C, LDL and TC). Spearman’s correlation demonstrated that vitamin D₃ status is strongly correlated with HDL levels (p < 0.05). Similarly, plasma total vitamin E levels >4.9 μg/mL revealed significantly different FBG, HbA1c, C-Peptide, LDL, HDL and TC levels across both groups. Moreover, family history, smoking, waist circumference and HbA1c levels demonstrated a significant association (p < 0.05) with levels of vitamins D and E but not FBG and lipid profiles. This could be because the pre-diabetic status among the non-DM group influenced the outcomes of this study.     

Vitamin D Nutritional Status of Chinese Pregnant Women,Comparing the Chinese National Nutrition Surveillance (CNHS) 2015–2017 with CNHS 2010–2012

Optimal vitamin D (vitD) status is beneficial for both pregnant women and their newborns. The aim of this study was to evaluate the vitamin D status of Chinese pregnant women in the latest China Nutrition and Health Surveillance (CNHS) 2015–2017, analyze the risk factors of vitamin D deficiency (VDD), and compare them with those in CNHS 2010–2012. Serum 25 hydroxyvitamin D (25(OH)D) was measured by ELISA method. City type, district, latitude, location, age, vitamin D supplements intake, education, marital status, annual family income, etc., were recorded. The median 25(OH)D concentration was 13.02 (10.17–17.01) ng/mL in 2015–2017, and 15.48 (11.89–20.09) ng/mL in 2010–2012. The vitamin D sufficient rate was only 12.57% in 2015–2017, comparing to 25.17% in 2010–2012. The risk factors of vitamin D inadequacy (25(OH)D < 20 ng/mL) in 2015–2017 were not exactly consistent with that in 2010–2012. The risk factors included season of spring (p < 0.0001) and winter (p < 0.001), subtropical (p < 0.001), median (p < 0.0001) and warm temperate zones (p < 0.0001), the western (p = 0.027) and the central areas (p = 0.041), while vitD supplements intake (p = 0.021) was a protective factor in pregnant women. In conclusion, vitD inadequacy is very common among Chinese pregnant women. We encourage pregnant women to take more effective sunlight and proper vitD supplements, especially for those from the subtropical, warm and medium temperate zones, the western and the central, and in the seasons of spring and winter.     

Effects of Vitamin D3 Supplementation and Resistance Training on 25-Hydroxyvitamin D Status and Functional Performance of Older Adults: A Randomized Placebo-Controlled Trial

Vitamin D status is associated with muscle strength and performance in older adults. To examine the additive effects of vitamin D3 supplementation during resistance training, 100 seniors (65–85 years) participated in a 16-week intervention. Besides a daily dose of 400 mg of calcium, participants received either 800 IU vitamin D3 per day (VDD), 50,000 IU vitamin D3 per month (VDM) or nothing (CON). After the initial loading phase of four weeks, all groups started a 10-week resistance training program. Assessments of 25-hydroxyvitamin D (25(OH)D) status, muscle strength endurance (30-s chair stand and arm curl tests), aerobic capacity (6-min walk test) and functional mobility (gait speed and timed up and go test) were undertaken at baseline, after four weeks and at the end of the study. 25(OH)D status significantly improved in VDD and VDM, but not in CON (time x group: p = 0.021), as 15.2% of CON, 40.0% of VDD and 61.1% of VDM reached vitamin D sufficiency (>30 ng/mL; p = 0.004). Chair stand test, arm curl test, 6-min walk test, gait speed and timed up and go test improved over the whole intervention period (p < 0.05), however only chair stand and arm curl test were selectively affected by resistance training (p < 0.001). Neither muscle strength endurance, nor functional mobility or aerobic capacity were modulated by vitamin D supplementation. Therefore, the mere amelioration of 25(OH)D status of older adults does not lead to an additive effect on muscular performance during RT.     

Dietary Alaska Pollack Protein Induces Acute and Sustainable Skeletal Muscle Hypertrophy in Rats

Our previous studies suggested that Alaska pollack protein (APP) intake increases skeletal muscle mass and that it may cause a slow-to-fast shift in muscle fiber type in rats fed a high-fat diet after 56 days of feeding. In this study, we explored whether dietary APP induces acute and sustainable skeletal muscle hypertrophy in rats fed a normal-fat diet. Male 5-week-old Sprague–Dawley rats were divided into four groups and fed a purified ingredient-based high-fat diet or a purified ingredient-based normal-fat diet with casein or APP, containing the same amount of crude protein. Dietary APP significantly increased gastrocnemius muscle mass (105~110%) after 2, 7 days of feeding, regardless of dietary fat content. Rats were separated into two groups and fed a normal-fat diet with casein or APP. Dietary APP significantly increased gastrocnemius muscle mass (110%) after 56 days of feeding. Dietary APP significantly increased the cross-sectional area of the gastrocnemius skeletal muscle and collagen-rich connective tissue after 7 days of feeding. It decreased the gene expression of Mstn /Myostatin, Trim63/MuRF1, and Fbxo32/atrogin-1, but not other gene expression, such as serum IGF-1 after 7 days of feeding. No differences were observed between casein and APP groups with respect to the percentage of Type I, Type IIA, and Type IIX or IIB fibers, as determined by myosin ATPase staining after 7 days of feeding. In the similar experiment, the puromycin-labeled peptides were not different between dietary casein and APP after 2 days of feeding. These results demonstrate that APP induces acute and sustainable skeletal muscle hypertrophy in rats, regardless of dietary fat content. Dietary APP, as a daily protein source, may be an approach for maintaining or increasing muscle mass.     

Association of Milk Consumption and Vitamin D Status in the US Population by Ethnicity: NHANES 2001–2010 Analysis

Vitamin D has been identified as a nutrient of public health concern, and higher intake of natural or fortified food sources of vitamin D, such as milk, are encouraged by the 2015–2020 Dietary Guidelines for Americans. We, therefore, examined the association of milk consumption and vitamin D status in the United States (US) population. Twenty-four-hour dietary recall data and serum 25(OH)D concentrations were obtained from the National Health and Nutrition Examination Survey 2001–2010 and were analyzed by linear and logistic regression after adjusting for anthropometric and demographic variables. Significance was set at p < 0.05. Approximately 57–80% children and 42–60% adults were milk consumers. Milk intake (especially reduced-fat, low fat and no-fat milk) was positively associated (p _{linear trend} < 0.05) with serum vitamin D status and with a 31–42% higher probability of meeting recommended serum vitamin D (>50 nmol/L) levels among all age groups. Serum vitamin D status was also associated with both type and amount of milk intake depending upon the age and ethnicity. In conclusion, the results indicate that milk consumers consistently have higher serum vitamin D levels and higher probability of meeting recommended levels. Therefore, increasing milk intake may be an effective strategy to improve the vitamin D status of the US population.     

Vitamin D Knowledge,Attitudes and Practices of Polish Medical Doctors

Background Vitamin D deficiency occurs in as much as 90–95% of the Polish population, although this condition is known to cause negative long-term health implications. The role of medical doctors in advising proper supplementation, monitoring and correcting the levels of 25-hydroxyvitamin D in individuals is of great importance and should be used to help mitigate its common deficits. The aim of this study was to evaluate knowledge, attitudes and practices of Polish physicians regarding vitamin D supplementation in order to identify areas for improvement and determinants for the knowledge gaps. Methods The study group comprised 701 medical doctors aged 32.1 ± 5.3 years on average, mostly women (71.61%). An original survey questionnaire was developed for the purpose of the study. Results The mean vitamin D knowledge score was 6.8 ± 2.3 (in a scale 0–13) and was related to gender (p < 0.001), type of specialization (p = 0.032), D3 supplements use (p < 0.001), recommending supplementation to patients (p = 0.005), to relatives and friends (p < 0.001) and to healthy adults (p < 0.001). In terms of self-administration, 14% of respondents take vitamin D all-year-round while 24% only in autumn and winter. 25% of respondents monitor their vitamin D (25-hydroxyvitamin D) serum concentration. Most participants (61%) did not recommend supplementing vitamin D to their patients on a regular basis. Conclusions The study indicates that medical doctors in Poland need to have more training and education on vitamin D supplementation in order to better address the problem of its deficits in the population.     

Obesity and Circulating Levels of Vitamin D before and after Weight Loss Induced by a Very Low-Calorie Ketogenic Diet

Background: Vitamin D plays a pivotal role in calcium and phosphorus metabolism, also influencing bone tissue. Several studies have reported that vitamin D blood levels were significantly lower in people with obesity, probably due to its uptake by the adipose tissue. Clinical studies that investigated the changes of circulating levels of vitamin D following weight loss reported controversial data. A very low-calorie ketogenic diet is acknowledged as a reliable treatment to achieve a rapid weight loss. Therefore, we investigated the effect of weight loss, consequent to a very low-calorie ketogenic diet, on vitamin D blood concentrations. Methods: A cohort of 31 people with obesity underwent a very low-calorie ketogenic diet for 10–12 weeks. The serum concentrations of vitamin D, parathormone, calcium and phosphorous were measured before and after weight loss; they were compared to a control group of 20 non-obese, non-diabetic, age- and gender-matched persons. Results: Patients with obesity had a higher habitual intake of vitamin D than the control group (p < 0.05). However, the vitamin D blood levels of the obese group were significantly lower than those of the control group (p < 0.005) and they increased after weight loss (p < 0.001). At baseline, vitamin D blood concentrations of the persons with obesity were significantly correlated with both fat mass–kg (r = −0.40; p < 0.05) and body mass index (r = −0.47; p < 0.01). Following very low-calorie ketogenic diet, the change in vitamin D serum concentrations was correlated only with the change in fat mass–kg (r = −0.43; p < 0.01). Conclusion: This study confirmed that patients with obesity have lower vitamin D levels that normalize after significant weight loss, supporting the hypothesis that vitamin D is stored in the adipose tissue and released following weight loss.     

25-Hydroxyvitamin D in Cancer Patients Admitted to Palliative Care: A Post-Hoc Analysis of the Swedish Trial ‘Palliative-D’

The purpose of this study is to explore 25-hydroxyvitamin D (25-OHD) levels in patients with cancer in the palliative phase in relation to season, sex, age, tumor type, colectomy, and survival. To this end, we performed a post-hoc analysis of ‘Palliative-D’, a randomized placebo-controlled, double-blind trial investigating the effect of daily supplementation with 4000 IU of vitamin D for 12 weeks on pain in patients in palliative cancer care. In the screening cohort (n = 530), 10% of patients had 25-OHD levels < 25 nmol/L, 50% < 50, and 84% < 75 nmol/L. Baseline 25-OHD did not differ between seasons or tumor type and was not correlated with survival time. In vitamin D deficient patients supplemented with vitamin D (n = 67), 86% reached sufficient levels, i.e., >50 nmol/L, after 12 weeks. An increase in 25-OHD was larger in supplemented women than in men (53 vs. 37 nmol/L, p = 0.02) and was not affected by season. In the placebo-group (n = 83), decreased levels of 25-OHD levels were noted during the study period for patients recruited during the last quarter of the year. In conclusion, cancer patients in palliative phase have adequate increase in 25-OHD after vitamin D supplementation regardless of season, age, tumor type, or colectomy.     

Cardiometabolic Indices after Weight Loss with Calcium or Dairy Foods: Secondary Analyses from a Randomized Trial with Overweight/Obese Postmenopausal Women

The role of dairy foods and calcium/vitamin D supplements in cardiometabolic diseases is unknown. The objective of this secondary analysis is to investigate cardiometabolic risk factors changes after a 6-month weight-loss intervention in overweight/obese postmenopausal women divided in three groups: Ca+vitamin D supplements (S); low-fat dairy foods (D; 4–5 servings/day); or control/placebo pills (C), as complements to hypocaloric diets. The original study focused on bone/body composition. This analysis included blood pressure (BP), and serum triglycerides, lipids (including apoproteins Apo1 and ApoB), adipokines, and C-reactive protein in n = 97 participants who finished with complete data points. Systolic BP decreased 5.1%, 4.8%, and 1.8% in S, D, and C groups, respectively (p < 0.05 for S and D vs. baseline and vs. C at 6 months). Reduction in triglycerides and ratio of total cholesterol (TC)/high-density lipoproteins cholesterol (HDL-C) was the highest in S, while the reduction in TC and LDL-C was the highest in D group (all p < 0.05). Leptin and ApoB significantly decreased and adiponectin and ApoA1 increased in all groups. In conclusion, although the C group’s participants experienced an improvement in some of the cardiometabolic indices with weight loss, those in the S and D groups showed significantly better results in most of the outcomes, indicating the beneficial effects of low-fat dairy foods and/or Ca+vitamin D intake as complements to a hypocaloric diet.     

Effects of Vitamin D Supplementation on 24-Hour Blood Pressure in Patients with Low 25-Hydroxyvitamin D Levels: A Randomized Controlled Trial

Accumulating evidence suggests that potential cardiovascular benefits of vitamin D supplementation may be restricted to individuals with very low 25-hydroxyvitamin D (25(OH)D) concentrations; the effect of vitamin D on blood pressure (BP) remains unclear. We addressed this issue in a post hoc analysis of the double-blind, randomized, placebo-controlled Styrian Vitamin D Hypertension Trial (2011–2014) with 200 hypertensive patients with 25(OH)D levels <30 ng/mL. We evaluated whether 2800 IU of vitamin D3/day or placebo (1:1) for 8 weeks affects 24-hour systolic ambulatory BP in patients with 25(OH)D concentrations <20 ng/mL, <16 ng/mL, and <12 ng/mL and whether achieved 25(OH)D concentrations were associated with BP measures. Taking into account correction for multiple testing, p values < 0.0026 were considered significant. No significant treatment effects on 24-hour BP were observed when different baseline 25(OH)D thresholds were used (all p-values > 0.30). However, there was a marginally significant trend towards an inverse association between the achieved 25(OH)D level with 24-hour systolic BP (−0.196 per ng/mL 25(OH)D, 95% CI (−0.325 to −0.067); p = 0.003). In conclusion, we could not document the antihypertensive effects of vitamin D in vitamin D-deficient individuals, but the association between achieved 25(OH)D concentrations and BP warrants further investigations on cardiovascular benefits of vitamin D in severe vitamin D deficiency.     

The Association between Serum Vitamin D Levels and Helicobacter pylori Presence and Eradication

Background: The success of Helicobacter pylori (H. pylori) eradication depends on several host and treatment factors. Serum vitamin D levels may be associated with H. pylori infection and eradication rates. We investigated the association between vitamin D and H. pylori infection and eradication, using a large electronic database based on medical records from a population-based health maintenance organization. Methods: Data regarding adults who underwent H. pylori testing and had vitamin D measurements within one month of H. pylori testing were collected. H. pylori infection was ascertained using urea breath or stool antigen tests. A negative H. pylori test following a positive result implied eradication. Multivariate regression models were constructed to assess associations between H. pylori infection, eradication, and vitamin D. Results: Among 150,483 members who underwent H. pylori testing from 2009 to 2018, 27,077 (18%) had vitamin D measurements. Vitamin D levels were inversely associated with H. pylori infection, p < 0.001. The odds of a positive H. pylori test were 31% higher among patients with vitamin D levels <20 ng/mL, compared with those with levels ≥20 ng/mL (OR 1.31, 99% CI 1.22–1.4, p < 0.001). Purchase of vitamin D supplements was associated with a negative subsequent H. pylori test (p < 0.001). Mean vitamin D levels were moderately higher in those with successful vs. failed H. pylori eradication (19.34 ± 9.55 vs. 18.64 ± 9.61, p < 0.001). Conclusions: Vitamin D levels are associated with H. pylori infection. Increased vitamin D levels are associated with successful H. pylori eradication. Vitamin D may have a role in H. pylori eradication.     

A Randomized Steady-State Bioavailability Study of Synthetic versus Natural (Kiwifruit-Derived) Vitamin C

Whether vitamin C from wholefoods has equivalent bioavailability to a purified supplement remains unclear. We have previously showed that kiwifruit provided significantly higher serum and tissue ascorbate levels than synthetic vitamin C in a genetically vitamin C-deficient mouse model, suggesting a synergistic activity of the whole fruit. To determine if these results are translatable to humans, we carried out a randomized human study comparing the bioavailability of vitamin C from kiwifruit with that of a vitamin C tablet of equivalent dosage. Thirty-six young non-smoking adult males were randomized to receive either half a gold kiwifruit (Actinidia Chinensis var. Hort 16A) per day or a comparable vitamin C dose (50 mg) in a chewable tablet for six weeks. Ascorbate was monitored weekly in fasting venous blood and in urine, semen, leukocytes, and skeletal muscle (vastus lateralis) pre- and post-intervention. Dietary intake of vitamin C was monitored using seven day food and beverage records. Participant ascorbate levels increased in plasma (P < 0.001), urine (P < 0.05), mononuclear cells (P < 0.01), neutrophils (P < 0.01) and muscle tissue (P < 0.001) post intervention. There were no significant differences in vitamin C bioavailability between the two intervention groups in any of the fluid, cell or tissue samples tested. Overall, our study showed comparable bioavailability of synthetic and kiwifruit-derived vitamin C.     

Lower Blood Vitamin D Levels Are Associated with Depressive Symptoms in a Population of Older Adults in Kuwait: A Cross-Sectional Study

Low serum vitamin D has been associated with an increased risk of neuropsychiatry disorders. This study aimed to examine the association between vitamin D deficiency and depression in adults aged 65 years and older. This cross-sectional study was conducted in seven primary healthcare centers across Kuwait (November 2020 to June 2021). The participants (n = 237) had their serum vitamin D 25-(OH)-D concentrations (analyzed by LC-MS) classified as sufficient, ≥75 nmol/L (30 ng/mL); insufficient, 50–75 nmol/L (20–30 ng/mL); or deficient, <50 nmol/L (20 ng/mL). Depressive symptoms were evaluated using the 15-Item Geriatric Depression Scale (15-item GDS). The mean serum 25-OH-D levels (nmol/L) in volunteers with normal, mild, moderate, and severe depression were 100.0 ± 31.7, 71.2 ± 38.6, 58.6 ± 30.1 and 49.0 ± 6.93, respectively (p < 0.001). The participants in the vitamin D sufficiency group were significantly less likely to exhibit depressive symptoms (88.2%) than patients with mild (36%) and moderate (21%) depression (p < 0.001). Ordinal logistic regression showed that vitamin D deficiency (OR = 19.7, 95% CI 5.60, 74.86, p < 0.001) and insufficiency (OR = 6.40, 95% CI 2.20, 19.91, p < 0.001) were associated with higher odds of having depressive symptoms. A low serum vitamin D level is a significant predictor of symptoms of depression among older individuals.     

Muscle fiber type IIX atrophy is involved in the loss of fat-free mass in chronic obstructive pulmonary disease

BACKGROUND: Although the loss of peripheral muscle mass has been shown convincingly in chronic obstructive pulmonary disease (COPD), the underlying pathogenesis remains unclear. OBJECTIVE: The aim of the present study was to determine the relations between skeletal muscle fiber types, fiber cross-sectional area (CSA), enzyme activities, and fat-free mass (FFM) in patients with COPD and in control subjects. DESIGN: In 15 patients with COPD and 15 healthy, age-matched control subjects, FFM was determined by dual-energy X-ray absorptiometry and bioelectrical impedance analysis. In biopsy specimens from the vastus lateralis fiber types, fiber CSA and activities of cytochrome oxidase (EC 1.9.3.1), succinate dehydrogenase (EC 1.3.99.1), and glycogen phosphorylase (EC 2.4.1.1) were examined immunohistochemically and histochemically. RESULTS: Compared with control subjects, patients with COPD had less FFM (49 compared with 59 kg, P = 0.030) and lower mean fiber CSA (3839 compared with 4647 microm(2), P = 0.037). A strong correlation (r = 0.87, P < 0.001) was observed between the FFM measured by bioelectrical impedance analysis and mean fiber CSA in patients with COPD. Within fiber-type categories the mean CSA of only the IIA/IIX and IIX fiber types was lower in patients than in control subjects [3358 compared with 4428 microm(2) (P = 0.022) and 2566 compared with 4248 microm(2) (P = 0.003), respectively]. In COPD, 20% of the type IIX fibers lacked stainable activities of cytochrome oxidase, succinate dehydrogenase, and glycogen phosphorylase, and this proportion correlated negatively with type IIX fiber CSA (r = -0.65, P = 0.012). CONCLUSIONS: Muscle fiber atrophy occurs in the vastus lateralis in patients with COPD and contributes to the loss of muscle mass in COPD. Atrophy is specific to fiber types IIA/IIX and IIX and is associated with a disturbed metabolic capacity.     

Moderate Amounts of Vitamin D3 in Supplements are Effective in Raising Serum 25-Hydroxyvitamin D from Low Baseline Levels in Adults: A Systematic Review

There is controversy surrounding the designation of vitamin D adequacy as defined by circulating levels of the metabolite 25-hydroxyvitamin D (25(OH)D). Depending on the cutoff level chosen, dietary intakes of vitamin D may or may not provide sufficient impact upon vitamin D status measured as improvement in serum levels of 25(OH)D. We sought to examine whether modest daily doses (5–20 μg) as found in fortified foods or multivitamin supplements had a measureable impact on vitamin D status, defined as moving from below to above 50 nmol/L, or from less than 30 nmol/L to above 30 nmol/L. Published literature was searched for relevant articles describing randomized controlled trials. Exclusion criteria were: studies not involving humans; review articles; studies lacking blood level data pre- and post-treatment; no control group; bolus treatments (weekly, monthly, yearly); vitamin D <5 μg or >20 μg; baseline 25(OH)D ≥75 nmol/L; subjects not defined as healthy; studies <8 weeks; and age <19 years. Of the 127 studies retrieved, 18 publications with 25 separate comparisons met criteria. The mean rate constant, defined as change in 25(OH)D in nmol/L per μg vitamin D administered, was calculated as 2.19 ± 0.97 nmol/L per μg. There was a significant negative correlation (r = −0.65, p = 0.0004) between rate constant and administered dose. To determine impact of the dose reflecting the Estimated Average Requirement (EAR) of 10 μg administered in nine studies (10 comparisons), in every case mean 25(OH)D status rose either from “insufficient” (30–50 nmol/L) to “sufficient” (>50 nmol/L) or from “deficient” (<30 nmol/L) to “insufficient” (>30 but <50 nmol/L). Our study shows that when baseline levels of groups were <75 nmol/L, for every microgram of vitamin D provided, 25(OH)D levels can be raised by 2 nmol/L; and further, when groups were deficient or insufficient in vitamin D, there was significant value in providing additional 10 μg per day of vitamin D.     

Serum Vitamin D Affected Type 2 Diabetes though Altering Lipid Profile and Modified the Effects of Testosterone on Diabetes Status

Numerous studies have investigated the associations between serum vitamin D or testosterone and diabetes; however, inconsistencies are observed. Whether there is an interaction between vitamin D and testosterone and whether the lipid profile (total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)) mediates the association between vitamin D and diabetes is unclear. To investigate the effect of vitamin D and testosterone on impaired fasting glucose (IFG) or type 2 diabetes mellitus (T2DM), 2659 participants from the Henan Rural Cohort were included in the case-control study. Generalized linear models were utilized to estimate associations of vitamin D with IFG or T2DM and interactive effects of vitamin D and testosterone on IFG or T2DM. Principal component analysis (PCA) and mediation analysis were used to estimate whether the lipid profile mediated the association of vitamin D with IFG or T2DM. Serum 25(OH)D₃, 25(OH)D₂, and total 25(OH)D levels were negatively correlated with IFG (odds ratios (ORs) (95% confidence intervals (CIs)): 0.99 (0.97, 1.00), 0.85 (0.82, 0.88), and 0.97 (0.96, 0.98), respectively). Similarity results for associations between serum 25(OH)D₂ and total 25(OH)D with T2DM (ORs (95%CIs): 0.84 (0.81, 0.88) and 0.97 (0.96, 0.99)) were observed, whereas serum 25(OH)D₃ was negatively correlated to T2DM only in the quartile 2 (Q2) and Q3 groups (both p < 0.05). The lipid profile, mainly TC and TG, partly mediated the relationship between 25(OH)D₂ or total 25(OH)D and IFG or T2DM and the proportion explained was from 2.74 to 17.46%. Furthermore, interactive effects of serum 25(OH)D₂, total 25(OH)D, and testosterone on T2DM were observed in females (both p for interactive <0.05), implying that the positive association between serum testosterone and T2DM was vanished when 25(OH)D₂ was higher than 10.04 ng/mL or total 25(OH)D was higher than 40.04 ng/mL. Therefore, ensuring adequate vitamin D levels could reduce the prevalence of IFG and T2DM, especially in females with high levels of testosterone.     

High Prevalence of Vitamin D Deficiency in Pregnant Korean Women: The First Trimester and the Winter Season as Risk Factors for Vitamin D Deficiency

We investigated the vitamin D status of Korean women during pregnancy and assessed the effects of vitamin D deficiency on two pregnancy outcomes; preterm births and the births of small for gestational age. We measured the serum 25-hydroxyvitamin D levels in 220 pregnant Korean women who were recruited prospectively and compared these levels with those of 500 healthy non-pregnant women. We analyzed vitamin D status according to patient demographics, season, and obstetrical characteristics; moreover, we also assessed pregnancy outcomes. The overall prevalence of vitamin D deficiency(<20 ng/mL) in pregnant women and healthy non-pregnant women was 77.3% and 79.2%; respectively; and the prevalence of severe vitamin D deficiency (<10 ng/mL) was 28.6% and 7.2%; respectively (p < 0.05). Vitamin D deficiency was more prevalent in the winter (100%) than in the summer (45.5%) in pregnant Korean women. A higher risk of vitamin D deficiency was observed in the first trimester than in the third trimester (adjusted OR 4.3; p < 0.05). No significant association was observed between vitamin D deficiency and any of the pregnancy outcomes examined. Further research focusing on the long-term consequences of vitamin D deficiency during pregnancy in Korean women is warranted.     

Effect of Type 2 Diabetes and Impaired Glucose Tolerance on Digestive Enzymes and Glucose Absorption in the Small Intestine of Young Rats

The reactions of intestinal functional parameters to type 2 diabetes at a young age remain unclear. The study aimed to assess changes in the activity of intestinal enzymes, glucose absorption, transporter content (SGLT1, GLUT2) and intestinal structure in young Wistar rats with type 2 diabetes (T2D) and impaired glucose tolerance (IGT). To induce these conditions in the T2D (n = 4) and IGT (n = 6) rats, we used a high-fat diet and a low dose of streptozotocin. Rats fed a high-fat diet (HFD) (n = 6) or a standard diet (SCD) (n = 6) were used as controls. The results showed that in T2D rats, the ability of the small intestine to absorb glucose was higher in comparison to HFD rats (p < 0.05). This was accompanied by a tendency towards an increase in the number of enterocytes on the villi of the small intestine in the absence of changes in the content of SGLT1 and GLUT2 in the brush border membrane of the enterocytes. T2D rats also showed lower maltase and alkaline phosphatase (AP) activity in the jejunal mucosa compared to the IGT rats (p < 0.05) and lower AP activity in the colon contents compared to the HFD (p < 0.05) and IGT (p < 0.05) rats. Thus, this study provides insights into the adaptation of the functional and structural parameters of the small intestine in the development of type 2 diabetes and impaired glucose tolerance in young representatives.