Suikerbuik
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There's written a lot on vitamin D and as it involves nutrition (and ultimately personal health) I think it's definitely worth posting here. This is another interesting EX VIVO study that doesn't support the view of targeting 40-50 ng/ml and covers some of the discussion points we had (see some quotes form the full-text below).
ABSTRACT
Prenatal vitamin D3 supplementation suppresses LL-37 peptide expression in ex vivo activated neonatal macrophages but not their killing capacity
Vitamin D has regulatory effects on innate immunity. In the present study, we aimed to assess the effect of prenatal vitamin D3 (vitD3) supplementation on neonatal innate immunity in a randomised, placebo-controlled trial by evaluating cathelicidin (LL-37) expression and the killing capacity of macrophages. Healthy pregnant women (n 129) attending a clinic in Dhaka were randomised to receive either a weekly oral dose of 0·875 mg vitD3 or placebo starting from 26 weeks of gestation up to delivery. Serum, plasma and monocyte-derived macrophages (MDM) were obtained from the cord blood. 25-Hydroxyvitamin D (25(OH)D) concentration was measured in serum. MDM were stimulated with or without Toll-like-receptor 4 ligand (TLR4L). Innate immune function was assessed by measuring LL-37 peptide levels in the culture supernatant of MDM by ELISA, LL-37 transcript levels by quantitative PCR, and ex vivo bactericidal capacity of MDM. vitD3 supplementation did not increase LL-37 peptide levels in plasma or in the extracellular fluid of macrophages with or without TLR4L induction. However, stimulated intracellular LL-37 expression (ratio of stimulated:unstimulated MDM) was significantly reduced in the vitamin D group v. placebo (P= 0·02). Multivariate-adjusted analyses showed that intracellular LL-37 peptide concentration from stimulated MDM was inversely associated with 25(OH)D concentration in serum (P= 0·03). TLR4L stimulation increased the bactericidal capacity of MDM compared with the unstimulated ones (P= 0·01); however, there was no difference in killing capacity between the two groups. A weekly dose of 0·875 mg vitD3 to healthy pregnant women suppressed the intracellular LL-37 peptide stores of activated macrophages, but did not significantly affect the ex vivo bactericidal capacity of cord blood MDM.
http://www.ncbi.nlm.nih.gov/pubmed/25089537
0.875 mg = ~34000 i.u. (per week)
I'll quote some statements or additional information on the subject from the full text:
So another decent study in which data supports against the use of suppletion, at least shows no single benefit from the use of vitamin D. And provides support to the view of healthy levels to be between 20- 30 ng/ml instead of levels >30 ng/ml.
ABSTRACT
Prenatal vitamin D3 supplementation suppresses LL-37 peptide expression in ex vivo activated neonatal macrophages but not their killing capacity
Vitamin D has regulatory effects on innate immunity. In the present study, we aimed to assess the effect of prenatal vitamin D3 (vitD3) supplementation on neonatal innate immunity in a randomised, placebo-controlled trial by evaluating cathelicidin (LL-37) expression and the killing capacity of macrophages. Healthy pregnant women (n 129) attending a clinic in Dhaka were randomised to receive either a weekly oral dose of 0·875 mg vitD3 or placebo starting from 26 weeks of gestation up to delivery. Serum, plasma and monocyte-derived macrophages (MDM) were obtained from the cord blood. 25-Hydroxyvitamin D (25(OH)D) concentration was measured in serum. MDM were stimulated with or without Toll-like-receptor 4 ligand (TLR4L). Innate immune function was assessed by measuring LL-37 peptide levels in the culture supernatant of MDM by ELISA, LL-37 transcript levels by quantitative PCR, and ex vivo bactericidal capacity of MDM. vitD3 supplementation did not increase LL-37 peptide levels in plasma or in the extracellular fluid of macrophages with or without TLR4L induction. However, stimulated intracellular LL-37 expression (ratio of stimulated:unstimulated MDM) was significantly reduced in the vitamin D group v. placebo (P= 0·02). Multivariate-adjusted analyses showed that intracellular LL-37 peptide concentration from stimulated MDM was inversely associated with 25(OH)D concentration in serum (P= 0·03). TLR4L stimulation increased the bactericidal capacity of MDM compared with the unstimulated ones (P= 0·01); however, there was no difference in killing capacity between the two groups. A weekly dose of 0·875 mg vitD3 to healthy pregnant women suppressed the intracellular LL-37 peptide stores of activated macrophages, but did not significantly affect the ex vivo bactericidal capacity of cord blood MDM.
http://www.ncbi.nlm.nih.gov/pubmed/25089537
0.875 mg = ~34000 i.u. (per week)
I'll quote some statements or additional information on the subject from the full text:
All major immune cells, including T cells, B cells, neutrophils and antigen-presenting cells (monocytes, macrophages and dendritic cells), express the vitamin D receptor. Macrophages, the front-line responders to microbial infection, sense pathogen-associatedmolecularpatterns by utilising pattern recognition receptors such as Toll-like receptors (TLR). TLR triggering induces Cytochrome p450 27B1 (CYP27B1), a vitamin D-activating enzyme that converts 25-hydroxyvitamin D (25(OH)D) into the active form (1,25-dihydroxyvitamin D; 1,25(OH)2D), and vitamin D receptor expression(3). The 1,25(OH)2D–vitamin D receptor complex directly induces cathelicidin antimicrobial peptide (CAMP; gene encoding LL-37) transcription and corresponding increases in the expression of the antimicrobial peptide, LL-37(4).
Cord serum 25(OH)D was not significantly associated with LL-37 concentration in the unstimulated ICF, or fold difference in intracellular LL-37 concentration (Table 2). However, 25(OH)D in cord serum was inversely related to TLR4L-induced intracellular LL-37 in both unadjusted bivariate and adjusted multivariate analyses (Table 2). For every 10 nmol/l increase in cord serum 25(OH)D concentration, TLR4L-induced intracellular LL-37 concentration decreased by 0·05 ng/ml (P¼0·03).
Upon stratifying the participants into four groups based on serum 25(OH)D concentrations, LL-37 peptide concentrations in the ICF of TLR4L-stimulated MDM were significantly reduced in the high (>76nmol/l), moderate (50–75 nmol/l) and low (30–49nmol/l) groups (P¼0·005, P¼0·035 and P¼0·029, respectively) compared with the very low (<30nmol/l) group (Fig. 1(a)).
the present study showed that prenatal vitD3 supplementation did not yield significant benefits in terms of indicators of innate immune function. In fact, we observed that vitD3 supplementation may have slightly suppressed intracellular LL-37 peptide synthesis in activated cord blood macrophages, suggesting a potential immunosuppressive effect. Furthermore, we did not find any significant influence of vitD3 supplementation on the bactericidal capacity of macrophages with or without TLR4L activation. In vitro studies using primary monocytes/macrophages cultured in 25(OH)D-sufficient sera or culture media containing the active form of vitamin D (1,25(OH)2D3) have shown that vitamin D mediates the induction of cathelicidin (LL-37) and b-defensin 4 transcripts in macrophages(3,24,25). In vitro addition of 1,25(OH)2D3 or 25(OH)D3 in cord blood cultures also showed increased TLR-independent or -dependent cathelicidin mRNA expression(23). In the present study, in vivo vitD3 supplementation did not affect LL-37 mRNA levels in neonatal macrophages with or without activation. The main difference between the other reports and the present study is that here vitD3 was given orally to pregnant women and autologous plasma was used instead of adding 1,25(OH)2D3 or 25(OH)D3 exogenously in the macrophage culture.
The present results thus collectively suggest that in vitro findings related to the effect of vitamin D metabolites on LL-37 expression may not be consistent and may not predict the in vivo effects of vitD3 supplementation,
In the abovementioned previous study involving healthy adult volunteers, we found that vitD3 supplementation significantly increased the antibacterial killing activity of macrophages in the absence of any increase in the levels of LL-37 peptide or mRNA expression(31). However, there are some key differences between our two studies. In our previous study(31), vitD3 supplementation was administered for only 4 d (even though the daily dose was the same), while in the present study, supplementation was given for about 3 months(19). The previous study involved healthy adults, while the participants of the present study were healthy pregnant women, and immune function was studied in cord blood, not in maternal specimens.
So another decent study in which data supports against the use of suppletion, at least shows no single benefit from the use of vitamin D. And provides support to the view of healthy levels to be between 20- 30 ng/ml instead of levels >30 ng/ml.