Magnesium is an important mineral for our metabolism. Besides its physiological function, the role of magnesium on vitamin D metabolism has been largely studied. It plays a role as an enzymatic cofactor in more than 300 metabolic reactions, and it's highly associated with bone health and homeostasis.
Vitamin D deficiency is usually approached simply by vitamin D supplementation, but this will be a total 'nonsense' if your magnesium levels are not enough.
In this post we'll take you through the interaction between magnesium and vitamin D to get an overview on how this mineral can affect vitamin D metabolism and serum levels
INTRODUCTION TO MAGNESIUM
Magnesium is the fourth most abundant minerals in our body. We contain nearly 25g magnesium, out of 99% is stored in bone, muscle and non-muscular tissue (study). The other 1% is found in serum and red blood cell, in where there are three categories of magnesium; free/ionized, protein bound and complexed with anions. Out of the three fractions, magnesium shows the highest bioavailability when complexed with anions (study)
Importance of Magnesium on the metabolism
Being the fourth most abundant metal cation in our body, magnesium plays important roles in our metabolism and health. It acts in more than 300 reactions, being present in some of the most important ones for our survival such as glyclolitic pathway, protein synthesis, or the processes forming the Central Dogma (study).
Acts as Cofactor for Biological Reactions
Due to its biochemical properties and electric charge (2+), it helps stabilize enzyme complexes -which present a negative charge under physiological conditions- to allow the reaction to proceed efficiently (study). Certain enzymes need of a magnesium molecule in order to catalyze the reaction.
To understand how the stabilization works, think of a magnet being attracted by another magnet of opposite pole. In biochemistry, negative and positive charges attract each other by the called ionic interactions and other weak non-covalent interactions. The formation of these interactions will help stabilizing the complex under physiological conditions (study)
Mantains body homeostasis
Magnesium (and metal cations in general) play an important role regulating osmotic gradients (study). This osmosis and water movement through internal tissues is crucial for mantaining a good cell environment and mantain pH levels and other conditions in range for efficienct metabolic rate (study)
Regulates Musle Function
Besides its role as a cofactor and mantaining body homeostasis, magnesium also interferes directly with biological systems. Among all the interactions, we wanted to highlight the regulatory role it plays on muscle function (welcome to your fitness website :)!).
Magnesium has been linked to Ca2+ transport in/out the sarcoplasmic reticulum (study), and this latter cation will regulate muscle contraction (study). In addition to that, magnesium is related to oxygen uptake and delivery on muscle cells, which potentially benefits muscle cell respiration and aerobic exercise (study). Magnesium also acts directly with muscle, enhacing nerve cells function and muscle contraction (study).
Its role as a cofactor will also optimize and enhance the glycolitic pathway, leading to a more efficient ATP production (study)
MAGNESIUM AND VITAMIN D
Vitamin D metabolism, as we saw HERE, refers to the different biochemical conversions to form the active vitamin D molecule and following washout. The efficiency and viability of these conversions will determine the bioavailability of vitamin D and to what extent it help us improve our health.
Magnesium is seen to play a role as a cofactor in nearly all reactions involved in vitamin D metabolism (study). Absence of this mineral in our organism will lead to unefficient vitamin D conversion into the active form and subsequent washout. So, even if we are supplementing with vitamin D, it won't be effective if we are magnesium deficient.
To understand this better, let's see the different reactions catalyzed by magnesium.
Vitamin D Metabolism: Overview
To briefly comment Vitamin D metabolism (more in depth HERE), it all starts by being synthesized from 7-dehydrocholesterol and UVB radiation (sunlight). That forms an inactive prohormone, previtamin D3, which converts in vitamin D3 by means of temperature stabilization. Once in our body, it's transported by VDBP through the plasma to the liver.
Once in the liver, the first conversion forms 25(OH)D, and circulating 25(OH)D is transported by VDBP to the kidney, in where its's converted to 1,25(OH)2D, the active form.
In the kidneys, the washout can also take place. Because it has to be a polar molecule in order to be removed by urine (it's an aqueous environment), 1,25(OH)2D is converted into 1,24,25(OH)3D. Similarly, 25(OH)D can be converted to 24,25(OH)D for vitamin D washout.
Vitamin D Metabolism
- Synthesis from 7-dehydrocholesterol
- Transport by VDBP to the liver
- Conversion to 25(OH)D
- Transport by VDBP to the kidneys
- Conversion to 1,25(OH)2D or 24,25(OH)2D
- Conversion to 1,24,25(OH)3D for washout
Magnesium on Vitamin D Metabolism
Magnesium is required in almost all reactions involving vitamin D metabolism (study). As you can see in the figure above, the reactions in where Magnesium needs to be present are:
- Conversion of vitamin D3 to 25(OH)D
- Conversion of 25(OH)D to 1,25(OH)2
- Conversion of 25(OH)D to 24,25(OH)2D
- Conversion of 1,25(OH)2D to 1,24,25(OH)3D
- Conversion of 24,25(OH)2D to 1,24,25(OH)3D
In addition to those conversions, magnesium is also needed for the synthesis of VDBP (study) and the synthesis and secretion of parathyroid hormone, which regulates the activity of the enzyme catalyzing the conversion of 25(OH)D into 1,25(OH)2D, the active form of vitamin D (study).
So, by looking at the interaction between magnesium and vitamin D metabolism, it is safe to conclude that absence or deficiency of magnesium leads to an unefficient vitamin D metabolism.
Vitamin D on Magnesium Metabolism
Not only magnesium affects vitamin D metabolism, but it happens the same the other way around. This interplay between both molecules is a widely seen metabolic interaction to regulate our metabolism and lower the risk of breaking body homeostasis.
Vitamin D, on its hand, improves intestinal absorption of magnesium by nearly 30% (study). And which is even better, this increased absorption didn't translate into a higher urinary magnesium. This means that retention of magnesium is also affected by means of vitamin D (study).
Vitamin D serum levels, therefore, affects magnesium metabolism. As magnesium deficiency can lead to vitamin D deficiency, the opposite can happen as well. To avoid, supplementing both vitamin D and magnesium can prevent deficiencies of any of these substances.
HOW TO SUPPLEMENT WITH MAGNESIUM AND VITAMIN D
Now you know the importance of having both micronutrients on range. Both vitamin D or magnesium deficiency will ultimately cause a deficiency on the other one.
Magnesium influences vitamin D metabolism by acting as a cofactor in all conversions to get the active form and washout. Not only that, but it's also required for the synthesis of VDBP and Parathyroid Hormone.
On the other hand, Vitamin D improves intestinal absorption of magensium and the retention in our organism.
Now the question is: what doses do I need of each to prevent deficiencies?
Vitamin D Supplementation
As we saw HERE, supplementing with vitamin D is the most efficient way to avoid deficiency. Due to limited sun exposure and low content on dietary sources, supplementation is the only way to achieve high doses of this vitamin.
In this study (done with pigs) doses of 1500-3000 UI/day were more effective than lower dosis at increasing magnesium absorption (study). When it comes to avoiding vitamin D deficiency, however, doses ranging from 1000 to 4000UI are used (study). Lack of studies regarding vitamin D supplementation for Magnesium deficiency don't enable us to conclude any ultimate guideline. But, for now, 2000-4000UI seem to be appropiate and effective at both improving magnesium absorption and increasing vitamin D serum levels.
In regards to timing, there are some insights into whether supplementing in the morning could be more benefitial. This speculation is based on the regulation of Circadian Rythms (read about it HERE), and the idea that high levels of vitamin D could simulate sunlight exposure and entrain Circadian Rythmicity. However, we are lacking studies investigating this, and we cannot conclude anything from a scientific point of view.
Serum levels of 0.75-0.95mmol/L of Magnesium are is considered the recommended range for a proper magnesium content in our body (study). Intake of magnesium-rich foods can help you avoiding deficiency. These include spinach, seeds, nuts, cocoa, whole grains, avocado, potato, rice and salmon. However, human hand on different foods has lowered the magnesium content by nearly 80% (study). This increases the risk of hypermagnesemia, and supplementation could come useful.
RDA and health organizations state daily doses of 400-420mg and 310-320mg for men and women, respectively (source). Based on this, we could see whether we are taking enough or lacking some magnesium in our diet. Supplementing with 200-400mg magnesium oxide (recommended formula) is efficient at increasing magnesium serum levels.
There's a huge heterogeneity on the different formulations for magnesium supplements. Showing different pharmacokynetics and bioavailabilty, it's important that you choose the right one. The two different forms are combined in inorganic or organic salts. The first ones show higher % of essential magnesium but lower bioavailability, while the latter show lower % of essential magnesium but higher bioavailability (study). Magnesium oxide, however, seems to be the best formulation (study)
Supplements providing both Magnesium and Vitamin D on the same capsule are rarely seen. Due to different biochemical properties, solubility and pharmacokynetics, it presents a big challenge when formulating the supplement. However, I want to highlight this supplement. It both provides the right doses of magnesium and vitamin D to prevent deficiencies and increase serum levels.
Magnesium and Vitamin D influence each other and potentiate the other's action. While magnesium is required for all conversion on vitamin D metabolism, the latter increases magnesium absorption and retention in our body.
In this post we have seen the importance of reaching recommended levels for both substances, and different supplements we could use to achieve this.
If you still have any questions regarding this topic, feel free to leave it below in the comments section.