Vitamin D deficiency is clearly linked to inflammation

Vitamin D deficiency plays a causative role in the systemic inflammation that commonly accompanies it, with a decrease in inflammation, reflected by reductions in elevated C-reactive protein (CRP), as vitamin D levels rise to at normal levels, new research shows.

However, there is no inverse effect between the two: changes in CRP levels did not appear to affect vitamin D levels.

“This is the first study of its kind and the first to show that the known relationship between vitamin D status and CRP is, at least in part, driven by vitamin D,” first author Elina Hypponen, PhD , professor of nutrition and said genetic epidemiology and director of the Australian Center for Precision Health in Adelaide, Australia Medscape Medical News.

“Since serum CRP level is a widely used biomarker for chronic inflammation, these results suggest that improving vitamin D status may reduce chronic inflammation, but only for people with vitamin D deficiency Hypponen and his co-authors report in their study, published in International Journal of Epidemiology.

Vitamin D associated with PCR a L-shaped way

Nutritional factors are known to influence systemic inflammation in several ways. However, there has been debate about the association between vitamin D, specifically serum 25(OH)D, an indicator of vitamin D status, and CRP, with some reports of observational associations between both contested in more robust randomized trials.

To further assess the relationship, the authors performed a two-way Mendelian randomization analysis, using a cohort of 294,970 unrelated participants of white/British ancestry in the UK Biobank, the largest cohort to date with measured serum concentrations of 25 (OH) D, they point out.

Overall, the median 25(OH)D concentration was 50.0 nmol/L (range 10–340 nmol/L), with 11.7% (n = 34,403) of participants having concentrations <25 nmol /L, considered deficient. Analysis showed that genetically predicted serum 25(OH)D was associated with serum L-shaped CRP, with CRP levels, and thus inflammation, decreasing sharply relative to increasing 25(OH)D concentration at normal levels.

However, the relationship was only significant among participants with 25(OH)D levels in the deficient range (< 25 nmol/L), with the association leveling off at around 50 nmol/L of 25(OH ) D, which is generally considered. a normal level.

The association was supported by further stratified Mendelian randomization analyses, which confirmed an inverse association between serum 25(OH)D in the deficient range and CRP, but not with higher serum vitamin D concentrations.

In contrast, neither linear nor nonlinear Mendelian randomization analyzes showed a causal effect of serum CRP level on 25(OH)D concentrations.

The results suggest that “improving vitamin D status in the deficient range could reduce low-grade systemic inflammation and potentially mitigate the risk or severity of chronic diseases with an inflammatory component,” the authors note.

Hypponen added that the greatest reductions in CRP are seen with correction of more severe vitamin D deficiency.

“The strongest benefits of improving concentrations will be seen for people with severe deficiency,” Hypponen said. Medscape Medical News.

“In our study, much of the benefit was achieved when people reached a cutoff of 50 nmol/L approved by the National Academy of Sciences. [for vitamin D sufficiency].”

Pro-hormonal effects?

The anti-inflammatory effects observed with serum vitamin D could be related to its role as a pro-hormone that can affect immune cells that express the vitamin D receptor, such as monocytes, B cells, T cells and antigen-presenting cells, according to the authors. note

“In fact, experiments with cells have shown that active vitamin D can inhibit the production of pro-inflammatory cytokines, such as TNF-alpha, interleukin (IL)-1b, IL-6, IL-8 and IL-12, and promote the production of IL-10, an anti-inflammatory cytokine,” they explain.

In this regard, adequate concentrations of vitamin D could be important to prevent inflammation-related complications from obesity and reduce the risk or severity of chronic diseases with an inflammatory component, such as cardiovascular disease, diabetes, autoimmune diseases , neurodegenerative conditions and others, the authors note.

Previous studies cannot assess the effect of the deficiency

Although the current findings contradict other studies that have used Mendelian randomization and showed no causal effect of 25(OH)D on CRP, these previous studies only used a standard linear Mendelian randomization method that could not rule out the possibility of a “threshold effect”. restricted to vitamin D deficiency, the authors note.

“Indeed, it is logical to expect that improvement in vitamin D status alone is relevant
the presence of vitamin D deficiency, while any further addition may be redundant and, at the extremes of supplementation, could become toxic,” they write.

However, the non-linear Mendelian randomization approach used in the current study allows for better detection of the association, and the authors note that the method has also recently been used in research showing an adverse effect of deficiency of vitamin D on the risk of cardiovascular disease (CVD). and mortality, which would not be visible using the standard Mendelian linear randomization approach.

Meanwhile, the current findings add to broader research showing that the benefits of vitamin D increases are mostly limited to those who are deficient, with limited benefit from supplementation for those who are not, Hypponen stressed. .

“We have repeatedly seen evidence of the health benefits of increasing vitamin D concentrations in individuals with very low levels, while for others, there appears to be little or no benefit,” Hypponen said in a press release.

“These findings highlight the importance of avoiding clinical vitamin D deficiency and provide further evidence for the broad effects of the vitamin D hormone,” he added.

The study was financially supported by the National Health and Medical Research Council, Australia. The authors have reported no relevant financial relationships.

Int J Epidemiol. Published online May 17, 2022. Full text

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