“Vitamin D metabolism and innate immunity”

In email from Pedro Carrrera Bastos.

Full text here.


Effects of vitamin D on the immune system have been recognized for over 30 years and stemmed in part from analysis of the dysregulated vitamin D metabolism associated with granulomatous diseases. How- ever, it is only in more recent years that a role for interaction between vitamin D and normal immune function has been proposed. As with the original studies, the basis for this new perspective on immuno- modulation by vitamin D stems from studies of vitamin D metabolism by immune cells. In particular, induction of the vitamin D-activating enzyme CYP27B1 in monocytes via pathogen recognizing receptors has highlighted an entirely new function for vitamin D as a potent inducer of antibacterial innate immune responses. This has prompted a new potential role for vitamin D in protecting against infection in a wide range of tissues but has also prompted revision of the parameters for adequate vitamin D status. The fol- lowing review describes some of the key developments in innate immune responses to vitamin D with particular emphasis on the role of key metabolic enzyme as determinants of localized immune activity of vitamin D.


The last 5 years have witnessed a sea-change in our perspective on how vitamin D interacts with the immune system. Prominent new data have shown that the expression and activity of vitamin D metabolizing enzymes is central to normal immune responses, providing a mechanism for localized metabolism of 25OHD to 1,25(OH)2D at sites of infection. Unlike its renal endocrine counter- part, the vitamin D metabolic machinery within the immune system is exquisitely dependent on the availability of substrate 25OHD – in other words the vitamin D status of any individual. Thus, impaired serum levels of 25OHD associated with vitamin D-insufficiency may lead to dysregulation of immune responses. Although this has consequences for both the innate and adaptive arms of the im- mune system, much recent attention has focused on antibacterial actions of vitamin D where intracrine coordination of monocyte CYP27B1 and VDR appears to be a central feature of innate immu- nity. Further characterization of vitamin D metabolism and innate immunity will be crucial in supporting a broader role for vitamin D in maintaining human health. At a basic science level, more infor- mation on the mechanisms that underpin immune regulation of en- zymes such as CYP27B1 and CYP24A1 is required. Likewise, almost all of the current data on how vitamin D can influence innate im- mune function has stemmed from studies of human cells. A limited number of animal models have been utilized with varying results (Schauber et al., 2007; Lagishetty et al., 2010b; Mathieu et al., 2001; Froicu and Cantorna, 2007), and future studies will need to improve this significantly. Finally, at a patient level more clinical tri- als are needed to determine how vitamin D affects infection in vivo, and whether the levels of vitamin D required to do this are the same as those required for classical skeletal functions of vitamin D.

I endeavor to spend as much time outdoors as I can, even in the winter in my backyard. No sunscreen ever, as sunscreen profits correlate 1:1 with melanoma. In addition, I supplement a few days per week with between four and eight thousand IU of D3. Have been doing so for years.

I typically feel good, never sick.

Since Covid killed my Cabo San Lucas vacation-rental business in 2021, this is my day job. I can't do it without you. Memberships are $10 monthly, $20 quarterly, or $65 annually. Two premium coffees per month. Every membership helps finance this work I do, and if you like what I do, please chip in. No grandiose pitches.

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