Vitamin D deficiency clearly linked to inflammation

Vitamin D Deficiency has a causative role in the systemic inflammation that usually accompanies it, with inflammation decreasing, reflected in reductions in elevated C-reactive protein (CRP), as vitamin D levels increase to normal levels , according to new research.

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

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

“Given that serum CRP 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. “, report Hypponen and his co-authors in their study. published in the International Journal of Epidemiology.

Vitamin D associated with CRP in L-shaped Way

Nutritional factors are known to influence systemic inflammation in various ways. However, there has been some 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 the two being challenged in more robust randomized trials.

To further assess the relationship, the authors performed a two-way Mendelian randomisation 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 note.

Overall, the mean 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.

The analysis showed that genetically predicted serum 25(OH)D was associated with L-shaped serum CRP, with CRP levels, and therefore inflammation, decreasing sharply with increasing concentration of 25 (OH)D at normal levels.

However, the relationship was only significant in participants whose 25(OH)D levels were in the deficiency range (< 25 nmol/L), with the association stabilizing at approximately 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 deficiency range and CRP, but not with higher serum vitamin D concentrations. .

Conversely, neither linear nor non-linear 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 deficiency range could reduce systemic low-grade inflammation and potentially ameliorate 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 the correction of the most severe vitamin D deficiency.

“The greatest benefits from improved concentrations will be seen in people with severe deficiency,” Hypponen said. Medscape Medical News.

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

Pro-hormonal effects?

The anti-inflammatory effects seen with serum vitamin D may be related to its role as a pro-hormone which may impact immune cells expressing vitamin D receptors, such as monocytes, B cells, T cells and antigen-presenting cells. Remark.

“Indeed, cellular experiments have shown that active vitamin D can inhibit the production of pro-inflammatory cytokines, including 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 in preventing inflammation-related complications. obesity and reduce the risk or severity of chronic diseases with an inflammatory component, such as cardiovascular disease, diabetes, autoimmune diseases, neurodegenerative diseases and others, note the authors.

Previous studies unable to assess effect of deficiency

While the current results contradict other studies that 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 exclude the possibility of a “threshold effect”. limited to vitamin D deficiency, the authors note.

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

However, the nonlinear Mendelian randomization approach used in the present study allows better detection of the association, and the authors point out that the method has also recently been used in research showing an adverse effect of vitamin D deficiency 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 increased vitamin D are mostly limited to those who are deficient, with limited benefit from supplementation for those who are not. , pointed out Hypponen.

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

“These results underscore the importance of avoiding clinical vitamin D deficiency and provide further evidence for the widespread effects of hormonal vitamin D,” she added.

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

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

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