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Magnesium intake modulates vitamin D status

Nutrients can often interact in our bodies in complex ways. This study found that magnesium intake influences vitamin D levels in complex ways that depend on baseline vitamin D status.

Study under review: Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial.

Introduction

Vitamin D plays many important roles[1] in the human body besides its well-known effect on bone health. Most cells, including those from the immune system, express the vitamin D receptor, highlighting the multiple roles of this vitamin for human health.

In humans, vitamin D is synthesized[2] from exposure to sunshine. Ultraviolet B radiation converts 7-dehydrocholesterol to previtamin D<sub>3</sub>, which is then rapidly converted to vitamin D<sub>3</sub>. Vitamin D can also be obtained through natural (fish, egg yolks, etc.) or fortified food sources (dairy, etc.) or supplements containing either D<sub>3</sub> or D<sub>2</sub>.

Two dietary sources of vitamin D

Vitamin D from food sources can be found in D<sub>2</sub> or D<sub>3</sub> forms. Vitamin D<sub>2</sub> is derived from UV-B irradiation of ergosterol in plants and fungi, which is why it’s called ergocalciferol. Conversely, cholecalciferol or vitamin D<sub>3</sub> is synthesized by the skin of animals, and it is the form in which vitamin D is found in animal foods (like egg yolks and fish). Although they are both very similar in structure, vitamin D<sub>2</sub> has an additional double bond and an extra methyl group, which affects its metabolism[2] and bioavailability. Compared to vitamin D<sub>3</sub>, vitamin D<sub>2</sub> is less efficient[3] at raising serum 25-OHD levels. Therefore, it is recommended that in addition to obtaining vitamin D from sun exposure, people’s vitamin D dietary intake should come preferentially from D<sub>3</sub> sources.

As shown in Figure 1, vitamin D is metabolized in the liver to 25-hydroxyvitamin D (25-OHD; the main storage form), levels of which are used to estimate a person’s vitamin D status, and further to the active form 1,25-OHD in the kidney by an enzyme called CYP27B1. On the other hand, CYP24A1 degrades both 25-OHD and 1,25-OHD, together with CYP3A4, into a biologically inactive, water soluble form (calcitroic acid). The activity of these enzymes control the levels of the active form of the vitamin (1,25-OHD) and prevent its toxic accumulation.

There appears to be an intimate relationship between several micronutrients and vitamin D. For example, vitamin D has been shown to increase calcium and phosphorus absorption[4]. Interestingly, there also appears to be an important relationship between magnesium and vitamin D. Some evidence suggests that vitamin D also increases magnesium absorption[5] and magnesium serves as a cofactor[6] for several enzymes involved in vitamin D metabolism. Furthermore, magnesium appears to influence the levels of vitamin D binding protein[7], which transports vitamin D in the blood. There is a type of magnesium-dependent[8] rickets, which highlights the importance of magnesium in vitamin D status.

Despite its physiologically important role, epidemiologic and randomized studies addressing the effect of vitamin D on bone fractures and extra skeletal chronic diseases (such as different types of cancer and cardiovascular disease) remain equivocal. Likewise, there appears to be unexplained heterogeneity between individuals in circulating levels of 25-OHD. A previous study[9] by the same authors observed an interaction between magnesium intake and vitamin D on mortality by cardiovascular disease and colorectal cancer show in Figure 2. A similar observation whereby magnesium intake modulated the risk of death associated with low vitamin D levels was published afterwards[10] in a different cohort of participants.


Given the observational relationship between magnesium levels and vitamin D status, as well as the importance of magnesium for vitamin D metabolism, the authors of the current study wanted to perform the first randomized controlled trial (RCT) on the effect of magnesium supplementation on vitamin D metabolism.

Vitamin D is a hormone that plays many roles in the human body. Despite its importance, results regarding its effects on skeletal and non-skeletal diseases remain equivocal. There appears to be an intricate relationship between magnesium and vitamin D, which may partly explain these inconsistent results. Some observational evidence also suggests an interaction between magnesium and vitamin D. As of now, there are yet no controlled trials that assess this relationship.

Two dietary sources of vitamin D

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Who and what was studied?

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The big picture

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