Vitamin D deficiency has a causal role in the systemic inflammation that commonly accompanies it, with decreased inflammation, reflected by reductions in elevated C-reactive protein (CRP), as vitamin D levels rise to normal levels , new research shows.
However, there is no reverse 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 known relationship between vitamin D status and CRP is driven, at least in part, 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.
“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 report. 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 a variety of 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 the two questioned in randomized trials more solid.
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 descent in the UK Biobank, the largest cohort to date with measured serum concentrations of 25(OH)D, point.
Overall, the mean 25(OH)D concentration was 50.0 nmol/L (range 10 to 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 L-shaped serum CRP, with CRP levels, and thus inflammation, dramatically decreasing in relation to increasing 25(OH) concentration. )D at normal levels.
However, the relationship was only significant among participants with 25(OH)D levels in the deficiency range (< 25 nmol/L), and the association plateaued at around 50 nmol/L 25(OH)D , which is generally considered a normal level
The association was supported by additional 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.
In contrast, neither linear nor nonlinear Mendelian randomization analyzes showed a causal effect of serum CRP level on 25(OH)D concentrations.
The findings suggest that “improving vitamin D status in the deficiency 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 the most severe vitamin D deficiency.
“The greatest benefits of improving 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 National Academy of Sciences-approved cutoff of 50 nmol/L [for vitamin D sufficiency].”
Pro-hormonal effects?
The anti-inflammatory effects observed with serum vitamin D could be related to its role as a prohormone 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, cell experiments have shown that active vitamin D can inhibit the production of proinflammatory cytokines, including TNF-alpha, interleukin (IL)-1b, IL-6, IL-8, and IL-12, and promote production of IL-10, an anti-inflammatory cytokine,” they explain.
In this sense, adequate concentrations of vitamin D could be important to prevent complications related to inflammation of the 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, the authors note.
Previous studies that could not assess the effect of deficiency
Although the current findings contradict other studies that used Mendelian randomization and did not show any causal effect of 25(OH)D on CRP, those earlier 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.
“In fact, it is logical to expect that improving vitamin D status would be relevant only in
the presence of vitamin D deficiency, while any further additions may be redundant and, at the…supplementation extreme, could become toxic,” they write.
However, the nonlinear Mendelian randomization approach used in the current study allows better detection of the association, and the authors note 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 linear Mendelian 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 health benefits from 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 news release.
“These findings highlight the importance of avoiding clinical vitamin D deficiency and provide additional evidence for the broad effects of the hormonal vitamin D,” he added.
The study was financially supported by the Australian National Health and Medical Research Council. The authors have disclosed that they have no relevant financial relationships.
Int J Epidemiol. Posted online May 17, 2022. Text complete
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