Scenario: Patient presents with low baseline 25(OH)D levels, let’s say 40 nmol/L and you prescribe a high  dose (e.g. 5000IU/day) bioavailable vitamin D supplement and retest in 3 months but the 25(OH)D levels haven’t improved…what do you do now?

Sound familiar?  It does to me. Once we have ruled out the usual suspects like taking the supplement at the wrong time (must be taken with a full stomach to ensure optimum fat digestion & uptake), inadequate dose (keep in mind that due to altered pharmacokinetics individuals with  obese BMI will require a significantly higher dose) etc. then according to new research from Deng et al. Magnesium, vitamin D status and mortality: results from US National Health and Nutrition Examination Survey (NHANES) 2001 to 2006 and NHANES III, we should be reviewing the patient’s magnesium status pronto! Deng et al remind us that magnesium is the co-factor for 3 critical enzymes central to vitamin D metabolism. Previous in vitro research suggests that magnesium status regulates both 1α-hydroxylase and 24-hydroxylase activity and the binding of vitamin D to its transport protein and 25-hydroxylase might also be magnesium dependent. You might remember as well that the synthesis and metabolism of PTH (the critical cue for activating 25(OH)D to 1,25(OH)2D are reliant on health magnesium status.

All in all this places magnesium front row for a starring role in vitamin D metabolism.

Only isolated previous research showed the strength of this relationship with a 1974 study describing ‘magnesium-dependent vitamin-D-resistant rickets’, which was effectively treated with magnesium & vitamin D, while vitamin D alone was completely ineffective. 

This recent research has demonstrated in a large cohort inadequate magnesium intake was more potently related to the presence of vitamin D insufficiency in individuals than vitamin D intake!

While this is only epidemiological research at this stage – it’s certainly a scientifically plausible concept and adds another element to the strong relationship between low 25(OH)D levels and increased all-cause mortality which numerous studies point to.

So next time when a patient’s 25(OH)D levels appear non-responsive to vitamin D supplementation – ask yourself, ‘Have they got enough magnesium?’

 Read the full paper by Deng et al here: