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Effect of a Hop Extract Standardized in 8-Prenylnaringenin on Bone Health and Gut Microbiome in Postmenopausal Women with Osteopenia: A One-Year Randomized, Double-Blind, Placebo-Controlled Trial.
Lecomte, M, Tomassi, D, Rizzoli, R, Tenon, M, Berton, T, Harney, S, Fança-Berthon, P
Nutrients. 2023;15(12)
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Osteoporosis is a bone condition characterized by weakened and brittle bones, leading to an increased risk of fractures. Oestrogens play a vital role in maintaining bone health, whereby oestrogen deficiency elevates the risk of osteoporosis and fractures, particularly in menopausal women due to the decline in oestrogen levels. Phytoestrogens, plant-derived compounds capable of interacting with human oestrogen receptors, have presented an intriguing non-pharmaceutical avenue for preventing bone loss. Other phytoestrogens have received some attention in the field, however, limited human research exists on prenylflavonoids, a phytoestrogens found in hops (Humulus lupulus). This randomized, double-blinded, placebo-controlled trial aimed to investigate the effects of a year-long supplementation of standardised hop extract (8-PN) Lifenol® on bone mineral density in postmenopausal women. Additionally, the study explored potential mechanisms, particularly focusing on changes in gut bacteria. Notably, gut bacteria play a role in bone metabolism and the pathogenesis of osteoporosis. They are also, along with the liver, responsible for converting hops phenols into active phytoestrogenic compounds. The trial was completed by 95 postmenopausal, women with Osteopenia aged 50 to 85. They all received calcium and vitamin D3 tablets in addition either a hop extract (100mcg) or a placebo for 48 weeks. Changes were monitored using DXA scans for bone mineral density (BMD) and bone metabolism, blood samples for markers for bone health, a quality of life questionnaire, gut microbiome testing, and tests for short-chain fatty acid (SCFA) levels. In conclusion, the intake of hop extract confirmed a previously observed trend of a slight increase in total bone mineral density (BMD), in addition to the benefits linked to calcium and vitamin D supplementation. Although there were no significant changes in the composition of gut bacteria and SCFA levels, the hop extract candidates had a higher abundance of specific genera associated with total body BMD, suggesting a potential positive impact. Larger studies are required to validate these findings.
Abstract
Estrogen deficiency increases the risk of osteoporosis and fracture. The aim of this study was to investigate whether a hop extract standardized in 8-prenylnaringenin (8-PN), a potent phytoestrogen, could improve bone status of osteopenic women and to explore the gut microbiome roles in this effect. In this double-blind, placebo-controlled, randomized trial, 100 postmenopausal, osteopenic women were supplemented with calcium and vitamin D3 (CaD) tablets and either a hop extract (HE) standardized in 8-PN (n = 50) or a placebo (n = 50) for 48 weeks. Bone mineral density (BMD) and bone metabolism were assessed by DXA measurements and plasma bone biomarkers, respectively. Participant's quality of life (SF-36), gut microbiome composition, and short-chain fatty acid (SCFA) levels were also investigated. In addition to the CaD supplements, 48 weeks of HE supplementation increased total body BMD (1.8 ± 0.4% vs. baseline, p < 0.0001; 1.0 ± 0.6% vs. placebo, p = 0.08), with a higher proportion of women experiencing an increase ≥1% compared to placebo (odds ratio: 2.41 ± 1.07, p < 0.05). An increase in the SF-36 physical functioning score was observed with HE versus placebo (p = 0.05). Gut microbiome α-diversity and SCFA levels did not differ between groups. However, a higher abundance of genera Turicibacter and Shigella was observed in the HE group; both genera have been previously identified as associated with total body BMD. These results suggest that an 8-PN standardized hop extract could beneficially impact bone health of postmenopausal women with osteopenia.
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Association of Vitamin D Level and Maternal Gut Microbiome during Pregnancy: Findings from a Randomized Controlled Trial of Antenatal Vitamin D Supplementation.
Aparicio, A, Gold, DR, Weiss, ST, Litonjua, AA, Lee-Sarwar, K, Liu, YY
Nutrients. 2023;15(9)
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Changes in the gut bacteria during pregnancy and a lack of vitamin D can have negative health consequences for both mother and child. Vitamin D has important functions in the human body and is key in regulating immune and inflammatory responses. Evidence suggests that vitamin D helps to maintain gut wall integrity and regulate inflammatory mechanisms in response to bacteria. Gut bacteria themselves have immune regulatory functions, and unfavourable disruptions in the composition of the bacteria are associated with chronic inflammatory diseases. Evidence shows gut bacteria composition is influenced by Vitamin D. During pregnancy, a substantial alteration in gut bacteria composition occurs and as pregnancy advances, there's typically an increase in bacteria linked to inflammation. This study analysed the data from the Vitamin D Antenatal Asthma Reduction Trial (VDAART, 2014), a randomised placebo controlled trial which gathered information on the impact of vitamin D on various markers as well as gut microbiome composition in pregnant women. For the study all participants took a daily multivitamin with 400 IU Vitamin D during the third trimester of pregnancy, and were given either an additional 4000IU of Vitamin D or a placebo. Results were drawn from 114 participants and their baseline vitamin D levels in early pregnancy, its changes over the trial period, as well as gut bacteria composition. The vitamin D levels at the start aligned with expected outcomes and was strongly linked to race, income, and education level. The baseline vitamin D level in early pregnancy also showed a connection to certain gut microbiome composition. However, these bacterial constellations remained robust and did not show any changes in response to Vitamin D supplementation throughout pregnancy. During the trial, most participant's vitamin D levels increased, especially those in the 4400 IU treatment group. Interestingly, women whose vitamin D levels did not increase much throughout the trial displayed a higher abundance of a bacteria called Desulfovibrio. Desulfovibrio is associated with an increased incidence of respiratory and inflammatory bowel diseases and the authors suggested that increasing vitamin D during pregnancy might help prevent the growth of more unfavourable bacteria like Desulfovibrio. Further long-term research is needed to confirm this idea.
Abstract
Shifts in the maternal gut microbiome and vitamin D deficiency during pregnancy have been associated, separately, with health problems for both the mother and the child. Yet, they have rarely been studied simultaneously. Here, we analyzed the gut microbiome (from stool samples obtained in late pregnancy) and vitamin D level (from blood samples obtained both in early and late pregnancy) data of pregnant women in the Vitamin D Antenatal Asthma Reduction Trial (VDAART), a randomized controlled trial of vitamin D supplementation during pregnancy, to investigate the association of vitamin D status on the pregnant women's microbiome. To find associations, we ran linear regressions on alpha diversity measures, PERMANOVA tests on beta diversity distances, and used the ANCOM-BC and Maaslin2 algorithms to find differentially abundant taxa. Analyses were deemed significant using a cut-off p-value of 0.05. We found that gut microbiome composition is associated with the vitamin D level in early pregnancy (baseline), the maternal gut microbiome does not show a shift in response to vitamin D supplementation during pregnancy, and that the genus Desulfovibrio is enriched in women without a substantial increase in vitamin D level between the first and the third trimesters of pregnancy. We conclude that increasing the vitamin D level during pregnancy could be protective against the growth of sulfate-reducing bacteria such as Desulfovibrio, which has been associated with chronic intestinal inflammatory disorders. More in-depth investigations are needed to confirm this hypothesis.
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REsCue trial: Randomized controlled clinical trial with extended-release calcifediol in symptomatic COVID-19 outpatients.
Bishop, CW, Ashfaq, A, Melnick, JZ, Vazquez-Escarpanter, E, Fialkow, JA, Strugnell, SA, Choe, J, Kalantar-Zadeh, K, Federman, NC, Ng, D, et al
Nutrition (Burbank, Los Angeles County, Calif.). 2023;107:111899
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Literature shows that vitamin D repletion may reduce the risk for infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mitigate severity of coronavirus disease (COVID-19), and accelerate recovery. Sufficient serum level of 25-hydroxyvitamin D (25D) is postulated to potentiate COVID-19 vaccine effectiveness, boost innate and control adaptive immunity, and reduce post-infection cytokine storm and lung injury. The aim of this study was to evaluate the safety and efficacy of extended-release calcifediol capsules to treat symptomatic patients infected with SARS-CoV-2. This study is a multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial titled REsCue. One hundred seventy-one symptomatic COVID-19 outpatients participants were enrolled. Patients were randomised (1:1) to 4 weeks of treatment with extended-release calcifediol (30 mcg/capsule) or matching placebo and a 2-week follow-up. Results show that extended-release calcifediol treatment was effective in increasing serum 25D levels to ≥50 ng/mL, which may have yielded significantly shorter resolution times for three aggregated respiratory symptoms (trouble breathing, chest congestion, and dry or hacking cough) commonly observed in patients with mild to moderate COVID-19. Authors conclude that the positive findings from this study warrant confirmation in additional larger studies.
Abstract
OBJECTIVES This double-blind randomized controlled trial investigated raising serum 25-hydroxyvitamin D (25D) with extended-release calcifediol (ERC) on time to symptom resolution in patients with mild to moderate COVID-19. METHODS COVID-19 outpatients received oral ERC (300 mcg on days 1-3 and 60 mcg on days 4-27) or placebo (NCT04551911). Symptoms were self-reported daily. Primary end points were raising 25D to ≥50 ng/mL and decreasing resolution time for five aggregated symptoms (three respiratory). RESULTS In all, 171 patients were randomized, 160 treated and 134 (65 ERC, 69 placebo) retained. The average age was 43 y (range 18-71), 59% were women. The mean baseline 25D was 37 ± 1 (SE) ng/mL. In the full analysis set (FAS), 81% of patients in the ERC group achieved 25D levels of ≥50 ng/mL versus 15% in the placebo group (P < 0.0001). In the per-protocol (PP) population, mean 25D increased with ERC to 82 ± 4 (SE) ng/mL (P < 0.0001) by day 7; the placebo group trended lower. Symptom resolution time was unchanged in the FAS by ERC (hazard ratio [HR], 0.983; 95% confidence interval [CI], 0.695-1.390; P = 0.922). In the PP population, respiratory symptoms resolved 4 d faster when 25D was elevated above baseline level at both days 7 and 14 (median 6.5 versus 10.5 d; HR, 1.372; 95% CI, 0.945-1.991; P = 0.0962; Wilcoxon P = 0.0386). Symptoms resolved in both treatment groups to a similar extent by study end. Safety concerns including hypercalcemia were absent with ERC treatment. CONCLUSION ERC safely raised serum 25D to ≥50 ng/mL in outpatients with COVID-19, possibly accelerating resolution of respiratory symptoms and mitigating the risk for pneumonia. These findings warrant further study.
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Circulating levels of maternal vitamin D and risk of ADHD in offspring: results from the Vitamin D Antenatal Asthma Reduction Trial.
Chu, SH, Huang, M, Kelly, RS, Kachroo, P, Litonjua, AA, Weiss, ST, Lasky-Su, J
International journal of epidemiology. 2022;51(3):910-918
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Acting as both a nutrient and a hormone, vitamin D has been found to play a critical role in neurodevelopment across sensitive periods in utero, infancy and early childhood. Among neurodevelopmental and behavioural disorders in early life, attention-deficit/hyperactivity disorder (ADHD) is the most common among children worldwide. Low levels of circulating 25-hydroxy-vitamin D [25(OH)D] have been shown to associate with prevalent ADHD. The aims of this study were to (i) determine the association between maternal vitamin D levels in the first and third trimesters of pregnancy and the risk of offspring ADHD by age 6 years or later; and (ii) to identify potential sensitive periods in utero during which vitamin D levels might be most important for reducing risk of ADHD. This is an ancillary study of the Vitamin D Antenatal Asthma Reduction Trial (VDAART). The VDAART was a randomised, double-blinded, multicentre, clinical trial in which 876 participating mothers were recruited between 10–18 weeks of gestation and assigned to receive either 4400 or 400 IU/day of vitamin D throughout pregnancy. Results show protective associations between maternal 25(OH)D sufficiency in the third trimester and child ADHD, but not at baseline. Furthermore, both at baseline and in the third trimester, there were higher odds of ADHD in male offspring as compared with female offspring with 25(OH)D insufficient mothers (analyses limited by small sample sizes) Authors conclude that higher levels of maternal vitamin D during pregnancy may play a protective role against risk of ADHD in offspring, but further studies are needed to confirm this association and any therapeutic potential therein.
Expert Review
Conflicts of interest:
None
Take Home Message:
Ensure that women in pregnancy, and possibly also those seeking to conceive, have adequate vitamin D status in order to reduce the risk of ADHD in offspring.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Background
This paper describes a secondary data analysis from an RCT that looked at the effect of prenatal vitamin D supplementation on risk of childhood asthma in offspring. Enrolled women aged 18–39 years with a history of asthma, eczema or allergic rhinitis, or whose partner (biological father of child) had a history of the aforementioned condition, received either 400 IU or 4400 IU vitamin D daily for the duration of their pregnancy. Offspring follow-up is still ongoing.
Aims
The current study aims were twofold: (i) to determine the association between maternal vitamin D levels in trimesters 1 and 3 and the risk of attention deficit/hyperactivity disorder (ADHD) in offspring diagnosed by age 6 years or later; and (ii) to identify potentially sensitive periods during gestation in which vitamin D levels may be especially important for reducing risk of ADHD.
Methods
The analytical sample included 679 mother-child pairs, from the original sample of 876 participating mothers. No sample size calculation was reported, though the sample was considered representative of the overall RCT study population.
Maternal vitamin D (serum 25(OH)D) was classified as follows
- Highly deficient <12 ng/mL
- Deficient 12 ng/mL to 19.9 ng/mL
- Insufficient 20 ng/mL to 29.9 ng/mL
- Sufficient ≥30 ng/mL
ADHD status was assessed through parental reporting between ages 6 and 9 years.
Results
No baseline associations between a vitamin D sufficient status and offspring ADHD in maternal samples collected during trimester 1 were observed (OR 1.06, 95% CI 0.51–2.19; P.0.871), though this association became statistically significant at trimester 3 (OR 0.47, 95% CI 0.26–0.84; P.0.011). This translated to a 53% less chance of having a child with ADHD at age 6 or later among mothers with vitamin D sufficiency compared with children of mothers with vitamin D deficiency. There was also a linear trend in the protective association of vitamin D sufficiency (≥30 ng/mL) on reduced risk of offspring ADHD at age 6 years or later in data from trimester 3. Stratified analyses revealed a protective association for sufficient maternal vitamin D status and offspring ADHD among males (OR 0.47, 95% CI 0.23–0.94).
Conclusions
The authors concluded that vitamin D sufficiency (≥30 ng/mL) in the 3rd trimester of gestation may decrease the risk of ADHD development in offspring.
Notes: The authors reported no relevant conflicts of interest.
Clinical practice applications:
Ensuring a sufficient vitamin D status by the 3rd trimester of pregnancy may help to lessen the risk of ADHD in offspring. Nutritional therapists and other clinicians working with pregnant women or women looking to conceive should consider checking vitamin D status and providing corrective supplementation and lifestyle advice to augment vitamin D levels where indicated.
Considerations for future research:
The authors of this study postulated that the statistically significant protective association between vitamin D at trimester 3 and ADHD in offspring was not significant in trimester 1 due to a low observed variability in vitamin D status (>75% of women were vitamin D insufficient), and thus the statistical test being underpowered to see difference between groups with sufficient or insufficient status.
Further research could expand upon this hypothesis to test whether vitamin D status in trimester 1, or preconceptually, may offer a protective association for ADHD and other related neurological conditions that may manifest in early life.
Abstract
BACKGROUND Low levels of circulating 25-hydroxy-vitamin D [25(OH)D] have been shown to associate with prevalent attention-deficit/hyperactivity disorder (ADHD), but few studies have examined the association between 25(OH)D during fetal development and risk of childhood ADHD. METHODS Maternal plasma 25(OH)D was measured at 10-18 and 32-38 weeks of gestation, with sufficiency defined as 25(OH)D ≥ 30 ng/ml. Offspring ADHD status between ages 6-9 years was measured by parent report of clinical ADHD diagnosis among 680 mother-child pairs from the Vitamin D Antenatal Asthma Reduction Trial. Association between maternal 25(OH)D and child ADHD was assessed using logistic regression, adjusting for maternal age, race and ethnicity. Effect modification by offspring sex was also assessed. RESULTS No associations between maternal 25(OH)D at 10-18 weeks of gestation and offspring ADHD were observed. In the third trimester, we observed associations between maternal vitamin D sufficiency and offspring ADHD [odds ratio (OR) 0.47, 95% confidence interval (CI) 0.26-0.84], in addition to maternal 25(OH)D sufficiency category, comparing the deficient (OR 0.34, 95% CI 0.12-0.94), insufficient (OR 0.41, 95% CI 0.15-1.10) and sufficient (OR 0.20, 95% CI 0.08-0.54) categories against highly deficient 25(OH)D, respectively. Stratified analyses revealed a protective association for sufficient maternal 25(OH)D and child ADHD among males (OR 0.47, 95% CI 0.23-0.94); the synergy index for additive effect modification of risk was 1.78 (95% CI 0.62-5.08). CONCLUSIONS Higher levels of maternal vitamin D in the third trimester are associated with lower risk of ADHD in offspring, with modest evidence for a stronger effect among male offspring. However, larger studies will be necessary to confirm these findings.
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The Impact of Vitamin D Supplementation on the IFNγ-IP10 Axis in Women with Hashimoto's Thyroiditis Treated with Levothyroxine: A Double-blind Randomized Placebo-controlled Trial.
Robat-Jazi, B, Mobini, S, Chahardoli, R, Mansouri, F, Nodehi, M, Esfahanian, F, Saboor Yaraghi, AA
Iranian journal of allergy, asthma, and immunology. 2022;21(4):407-417
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Hashimoto’s thyroiditis is an autoimmune disease characterized by the presence of antibodies against thyroid proteins such as thyroperoxidase (TPO) and thyroglobulin (TG), the local accumulation of inflammatory cells and immune-mediated destruction of the thyroid gland. Disease manifestation is due to a genetic disposition but is also influenced by several environmental factors, including stress, smoking, infections, and levels of nutrients like iodine, selenium and vitamin D. Many cells of the immune system have receptors for Vitamin D and thus have the potential to be influenced by Vitamin D. Indeed, numerous findings demonstrated that vitamin D can exert anti-inflammatory effects on the immune system. This double-blind, randomized, placebo-controlled trial investigated 40 Hashimoto's thyroiditis subjects and the effect of Vitamin D supplementation on various markers of the immune system that mediate the inflammatory response as part of the interferon-gamma-induced protein 10 (IFNγ-IP10) axis. 20 of the enrolled candidates received 50000 IU of Vitamin D (cholecalciferol) once a week – an equivalent to about 7140 IU per day - over three months. The other half received a placebo. All candidates had a fixed dose of thyroid hormone replacement levothyroxine for the duration of the trial. Before and after the intervention several blood biomarkers were investigated relating to Vitamin D levels, D-receptors, immune activity and inflammation. Upon completion of the trial, the intervention group who supplemented Vitamin D had significantly higher Vitamin D levels, which had increased from an average of 25.29 ng/ml to 50.65ng/ml. In addition, several inflammatory factors were significantly decreased. These findings affirmed Vitamin D’s ability to favourably regulate the IFNγ-IP10 axis, which could slow disease progression. This effect may also be useful for the management of other autoimmune disorders involving IP10 overproduction, which attracts other inflammatory cells. More studies in larger groups would help to get more information on other variables not considered in this trial.
Abstract
Hashimoto's thyroiditis (HT) results from chemoattraction of inflammatory cells toward the thyroid gland by inducing the production of interferon-gamma (IFNγ)-induced protein 10 (IP10) by T helper (Th) 1 cells. Vitamin D may suppress the IFNγ-IP10 axis, but this new function of vitamin D has not yet been investigated in HT patients. In an intervention and control group, patients received 50000 IU cholecalciferol or placebo every week for three months, respectively. The CD4+ T cells of 40 patients were isolated, and the mRNA expression levels of vitamin D receptor (VDR), peroxisome proliferator-activated receptors (PPAR)-α, and PPAR-γ genes were determined by real-time PCR. ELISA method was used to determine serum levels of vitamin D, tumor necrosis factor-alpha (TNF-α), IFN-γ, and IP10. Vitamin D levels in the intervention group were significantly higher than in the placebo group after supplementation. PPAR-α and PPAR-γ gene expression levels did not differ significantly between the two groups. The serum levels of IP10, IFNγ, and TNF-α decreased significantly in the vitamin D group, as well as in the placebo group. During this study, vitamin D levels significantly increased in the intervention group and inflammatory factors decreased. Based on the similar results obtained in the placebo group, further studies with larger sample sizes and longer intervention times are recommended.
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Safety and tolerability of 6-month supplementation with a vitamin D, calcium and leucine-enriched whey protein medical nutrition drink in sarcopenic older adults.
Bauer, JM, Mikušová, L, Verlaan, S, Bautmans, I, Brandt, K, Donini, LM, Maggio, M, Mets, T, Wijers, SLJ, Garthoff, JA, et al
Aging clinical and experimental research. 2020;32(8):1501-1514
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Older adults who have sarcopenia and osteoporosis are at risk of falls, fractures and hospitalisation. Sufficient dietary protein intake and an adequate vitamin D and calcium status has been proposed as a way to attenuate age-related loss of muscle and bone. This however may cause safety concerns with regard to kidney function and potential vitamin D or calcium toxicity. The aim of this randomised placebo-controlled trial was to determine the effect of 6 months supplementation with a vitamin D, calcium and leucine-enriched whey protein medical nutrition drink (WP-MND) on kidney function and on vitamin D, parathyroid hormone (PTH) and calcium levels in sarcopenic older adults. In conclusion, a 6-month intake of a vitamin D, calcium and leucine-enriched whey protein medical nutrition drink in addition to a regular diet does not impair kidney function or disturb vitamin D and calcium metabolism in sarcopenic older adults.
Abstract
AIMS: Safety and tolerability of prolonged supplementation with a vitamin D, calcium and leucine-enriched whey protein medical nutrition drink (WP-MND) was evaluated in sarcopenic older adults. METHODS A 13-week double-blinded, randomized, isocaloric placebo-controlled trial (PROVIDE study; n = 380) was extended with a voluntary 13-week open-label extension (OLE). OLE participants were randomized to receive daily 1 or 2 servings of WP-MND (21 g protein, 3 g leucine, 10 µg vitD and 500 mg calcium per serving). Gastro-intestinal tolerability, kidney function and serum levels of calcidiol, parathyroid hormone (PTH) and calcium were evaluated at week 0, 13 and 26. RESULTS AND DISCUSSION In response to the high daily protein intake (median1.5; IQR: 1.3, 1.7 g/kg BW/day), the estimated glomerular filtration rate (eGFR) increased in the test group during the RCT (p = 0.013). The same trend was observed for those participants with moderate chronic kidney disease. During OLE no eGFR change was observed in any of the groups. Serum calcidiol and calcium reached a plateau after 13-week WP-MND supplementation. As expected, PTH significantly changed in the opposite direction, decreasing during RCT in the test group (T vs C: p < 0.001) and during OLE in former control groups. During RCT, 20/366 participants with normal baseline calcidiol reached levels ≥ 100 nmol/L (T: n = 18; C: n = 2) and 6 developed albumin-corrected calcium levels > 2.55 mmol/L (T: n = 3; C: n = 3), without associated adverse events. CONCLUSION A 6 months intervention with up to 2 servings of WP-MND did neither result in kidney function deterioration nor symptoms of vitamin D or calcium toxicity. The product was overall well tolerated.
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Vitamin D supplementation improves SIRT1, Irisin, and glucose indices in overweight or obese type 2 diabetic patients: a double-blind randomized placebo-controlled clinical trial.
Safarpour, P, Daneshi-Maskooni, M, Vafa, M, Nourbakhsh, M, Janani, L, Maddah, M, Amiri, FS, Mohammadi, F, Sadeghi, H
BMC family practice. 2020;21(1):26
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Type 2 diabetes (T2D) is often preceded by a condition known as insulin resistance (IR). Recent studies have shown that low levels of vitamin D in the body are related to an increased incidence of IR and individuals with T2D have lower levels of vitamin D than healthy individuals. Vitamin D may have the ability to increase enzymes in the body that breakdown sugar and decrease IR. This 12-month double blind randomised control trial on 90 obese type 2 diabetics, aimed to assess the effects of vitamin D on these enzymes and blood sugar levels. The results showed that individuals on vitamin D had significantly increased enzymes which are involved in sugar breakdown and this translated into improved blood sugar levels, however this did not translate into improved markers for IR. It was concluded that compared to placebo, vitamin D supplementation improved blood sugar levels possibly due to the increase in enzymes involved in sugar breakdown. Healthcare professionals could use this study to recommend vitamin D supplementation to obese type 2 diabetics to improve their blood sugar levels.
Abstract
BACKGROUND Vitamin D (VD) may increase sirtuin 1 (SIRT1) and subsequently PPAR-γ coactivator 1α (PGC-1α) and irisin levels and these improvements may reduce insulin resistance (IR). The aim was to assess the effects of vitamin D supplementation on SIRT1, irisin, and IR in overweight/obese type 2 diabetes (T2D) patients. METHODS Ninety T2D males and females were recruited as a clinical trial study (mean of age and body mass index (BMI) of intervention and placebo groups were 50.05 ± 10.17 and 50.36 ± 10.2 yrs. and 31.37 ± 3.4 and 30.43 ± 3.2 kg/m2, respectively). The inclusion criteria were T2D, VD deficient, BMI > 25 kg/m2, and serum HbA1c < 8.5%. The exclusion criteria were using vitamin and mineral supplements, having any acute disease, recent modifying dose or type of drugs. The supplementation was 50,000 IU/week VD or placebo for 8 weeks. The demographic characteristics, anthropometrics, dietary intakes and physical activity status, sun exposure status, fasting blood sugar (FBS) and insulin, glycosylated hemoglobin (HbA1c), irisin, SIRT1, 25-hydroxy D3 (25(OH)VD), homeostasis model assessment of insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI) were determined. The significant P-value was ≤0.05. RESULTS The increase of serum VD, SIRT1, and irisin in the intervention group was significant (p < 0.001). HbA1c was decreased significantly by 1%. The changes in the other glucose indices (FBS, insulin, and IR) were non-significant. CONCLUSIONS VD supplementation may improve T2D by decreasing HbA1c and increasing SIRT1 and irisin in VD deficient T2D patients. Further trials are suggested. TRIAL REGISTRATION Iranian Registry of Clinical Trials, IRCT201604202365N11. Registered 21/08/2016, http://en.irct.ir/trial/2019.
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Improving rehabilitation in sarcopenia: a randomized-controlled trial utilizing a muscle-targeted food for special medical purposes.
Rondanelli, M, Cereda, E, Klersy, C, Faliva, MA, Peroni, G, Nichetti, M, Gasparri, C, Iannello, G, Spadaccini, D, Infantino, V, et al
Journal of cachexia, sarcopenia and muscle. 2020;11(6):1535-1547
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Sarcopenia is a condition characterised by loss of muscle mass in older adults. Current treatment consists of targeting muscle mass and function via physical exercise, optimisation of protein intake and vitamin D supplementation; but evidence is lacking. The purpose of this double blind, randomised controlled trial was to assess the efficacy of a muscle‐targeted nutritional supplement on physical performance and muscle mass recovery in older sarcopenic patients admitted to an in‐patient rehabilitation facility, as well as to gather information on its economic benefits. 140 older adults took part in the trial. The intervention group consumed a whey protein-based nutritional formula with added leucine and vitamin D twice a day. The control group consumed an isocaloric formula. The intervention group significantly improved their gait speed. A substantial increase in muscle mass was also obtained. These patients also required significantly less rehabilitation than the patients in the control formula group and were discharged earlier. In old adults with sarcopenia admitted to hospital for rehabilitation the consumption of a whey protein‐based nutritional formula enriched with leucine and vitamin D improved physical performance and function, as well as muscle mass, and reduced the intensity and costs of care.
Abstract
BACKGROUND Sarcopenia is a disease associated with aging and a negative prognosis. Consensus-based treatment consists in targeting muscle mass and function through physical exercise, optimization of protein intake, and vitamin D supplementation, but evidence is lacking. We evaluated the safety and efficacy of a muscle-targeted nutritional support on the outcome of a physical exercise rehabilitation programme. METHODS In a single-site, double-blind, randomized, controlled trial (NCT03120026; May 2017 to December 2018), old (≥65 years) adults [N = 140 (63% female patients; age, 81 ± 6 years)] without severe cognitive impairment, who were found to have sarcopenia by European Working Group on Sarcopenia in Older People 2010 criteria and hospitalized for physical rehabilitation, were randomized to receive until discharge (for at least 4 weeks and up to 8 weeks) a whey protein-based nutritional formula enriched with leucine and vitamin D or an iso-caloric control formula twice daily in addition to a standard hospital diet. The primary endpoint was the change in 4 m gait speed per month. Key secondary endpoints addressed the change in physical performance: chair-stand test, timed up and go test, and short physical performance battery. Other secondary outcomes were the change in functional status, muscle strength and mass, cognitive status, and quality of life. The proportion of patients who improved their rehabilitation intensity profile and overall economic benefits (using length of stay and duration of rehabilitation as surrogate measures) were also evaluated. RESULTS A total of 161 patients were screened and 140 were randomized to study interventions. Thirteen patients (experimental, n = 6; placebo, n = 7) discontinued the intervention because they disliked the product and intention-to-treat analyses were based on patients reassessed at discharge [n = 127 (66% female patients; age, 81 ± 6 years)]. Supplementation with the experimental formula (n = 64) resulted in greater increase in mean gait speed {0.061 m/s/month [95% confidence interval (CI), 0.043 to 0.080]} than placebo [n = 63; -0.001 m/s/month (95%CI, -0.008 to 0.006)]: mean difference, 0.063 m/s/month (95%CI, 0.043 to 0.082) (P < 0.001). A significant effect was also found for muscle mass (P < 0.03) and all key secondary outcomes, functional and cognitive endpoints (P < 0.001 for all). Supplementation resulted also in higher proportion of patients improving their rehabilitation intensity profile (P = 0.003) and being discharged home (P = 0.002); shorter rehabilitation (P < 0.001); and hospital stay (P < 0.001). CONCLUSIONS In old adults with sarcopenia admitted to hospital for rehabilitation the consumption of a whey protein-based nutritional formula enriched with leucine and vitamin D improved physical performance and function, as well as muscle mass, and reduced the intensity and costs of care.
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Vitamin B12 Status Upon Short-Term Intervention with a Vegan Diet-A Randomized Controlled Trial in Healthy Participants.
Lederer, AK, Hannibal, L, Hettich, M, Behringer, S, Spiekerkoetter, U, Steinborn, C, Gründemann, C, Zimmermann-Klemd, AM, Müller, A, Simmet, T, et al
Nutrients. 2019;11(11)
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Veganism is growing in western societies and with it comes an increased risk of vitamin B12 deficiency which is principally found in animal products. Vitamin B12 is essential for multiple biological functions including DNA synthesis, digestive function and detoxification processes. It can take 2-5 years to exhaust natural stores of B12 within the body so deficiency risk is considered safe. This 2017 randomised control trial compared vitamin B12 status in 53 healthy omnivore subjects with 26 participants following an unsupplemented vegan diet for 4 weeks and the remaining 27 participants a meat-rich diet. The aim of the study was to answer two questions; (a) Do vitamin B12 markers respond to short-term dietary intervention with a meat-rich or a plant-based diet? and (b) Do meat-rich and vegan diets have an impact on plasma markers of inflammation and cardiovascular disease? Blood and urine samples were taken before and after the 4-week dietary protocol to also measure vitamin D status, Folate and Homocysteine levels as a marker for inflammation. The serum vitamin B12 levels (indicative of dietary B12) dropped significantly from 362.9 +/- 110.9 ng/mL to 296.1 +/- 94.1 ng/mL in the Vegan Diet group (p < 0.001) and remained stable in the Meat Diet group. Other markers measuring cellular B12 metabolism did not significantly vary. The short-term nature of the trial demonstrated rapid decrease in holo-TC, the bioactive form of vitamin B12 in plasma. The other blood and urinary markers demonstrated benefits to plant-based eating including reduced cholesterol intake and adequate profiles of nutrient and micronutrient status.
Abstract
Vegans are at an increased risk for certain micronutrient deficiencies, foremost of vitamin B12. Little is known about the short-term effects of dietary change to plant-based nutrition on vitamin B12 metabolism. Systemic biomarkers of vitamin B12 status, namely, serum vitamin B12 and holotranscobalamin, may respond quickly to a reduced intake of vitamin B12. To test this hypothesis, 53 healthy omnivore subjects were randomized to a controlled unsupplemented vegan diet (VD, n = 26) or meat-rich diet (MD, n = 27) for 4 weeks. Vitamin B12 status was examined by measurement of serum vitamin B12, holotranscobalamin (holo-TC), methylmalonic acid (MMA) and total plasma homocysteine (tHcy). Holo-TC decreased significantly in the VD compared to the MD group after four weeks of intervention, whereas metabolites MMA and tHcy were unaffected. Body weight remained stable in both groups. VD intervention led to a significant reduction of cholesterol intake, and adequate profiles of nutrient and micronutrient status. Lower intake of vitamin B12 was observed in VD, which was mirrored by a lower concentration of serum vitamin B12 and reduced holo-TC after 4 weeks. Plasma holo-TC may be a fast-responding biomarker to monitor adequate supply of vitamin B12 in plant-based individuals.
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Impact of Vitamin D Supplementation on Influenza Vaccine Response and Immune Functions in Deficient Elderly Persons: A Randomized Placebo-Controlled Trial.
Goncalves-Mendes, N, Talvas, J, Dualé, C, Guttmann, A, Corbin, V, Marceau, G, Sapin, V, Brachet, P, Evrard, B, Laurichesse, H, et al
Frontiers in immunology. 2019;10:65
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This randomized placebo-controlled double-blind trial investigated whether Vit-D supplementation in a sample of 38 deficient elderly persons, over 65-year olds, could improve influenza seroprotection and immune response. Vitamin D is known to both potentiate the innate immune response and inhibit the adaptive system, and so potentially modulate vaccination response. The participants were randomised into two arms: vitamin D supplementation group (D) and placebo group (P). The D group received 100,000 IU/15 days of cholecalciferol over a 3-month period after which both groups were given the influenza vaccine, and their blood was evaluated 28 days later. Several immune biomarkers were analysed including plasma cytokine profiles, phagocyte ROS production, and lymphocyte cells phenotyping to determine if Vitamin D enhanced immune response to the vaccination. No differences were found in serum ROS and antibody markers. However, Vitamin D supplementation did promote a higher TGFβ plasma level in response to influenza vaccination. Taken together, these results suggest that vitamin D supplementation is not an effective way to improve antibody response to influenza vaccine in deficient elderly people.
Abstract
Background: Immunosenescence contributes to reduced vaccine response in elderly persons, and is worsened by deficiencies in nutrients such as Vitamin (Vit-D). The immune system is a well-known target of Vit-D, which can both potentiate the innate immune response and inhibit the adaptive system, and so modulate vaccination response. Objective: This randomized placebo-controlled double-blind trial investigated whether Vit-D supplementation in deficient elderly persons could improve influenza seroprotection and immune response. Design: Deficient volunteers (Vit-D serum <30 ng/mL) were assigned (V1) to receive either 100,000 IU/15 days of cholecalciferol (D, n = 19), or a placebo (P, n = 19), over a 3 month period. Influenza vaccination was performed at the end of this period (V2), and the vaccine response was evaluated 28 days later (V3). At each visit, serum cathelicidin, immune response to vaccination, plasma cytokines, lymphocyte phenotyping, and phagocyte ROS production were assessed. Results: Levels of serum 25-(OH)D increased after supplementation (D group, V1 vs. V2: 20.7 ± 5.7 vs. 44.3 ± 8.6 ng/mL, p < 0.001). No difference was observed for serum cathelicidin levels, antibody titers, and ROS production in D vs. P groups at V3. Lower plasma levels of TNFα (p = 0.040) and IL-6 (p = 0.046), and higher ones for TFGβ (p = 0.0028) were observed at V3. The Th1/Th2 ratio was lower in the D group at V2 (D: 0.12 ± 0.05 vs. P: 0.18 ± 0.05, p = 0.039). Conclusions: Vit-D supplementation promotes a higher TGFβ plasma level in response to influenza vaccination without improving antibody production. This supplementation seems to direct the lymphocyte polarization toward a tolerogenic immune response. A deeper characterization of metabolic and molecular pathways of these observations will aid in the understanding of Vit-D's effects on cell-mediated immunity in aging. This clinical trial was registered at clinicaltrials.gov as NCT01893385.