In people with type 2 diabetes and early kidney disease, those with higher levels of vitamin D-binding protein in their blood at the start of treatment are less likely to reach healthy vitamin D...
Mechanism
Synthesis from 1 study
High levels of a blood protein trap vitamin D from supplements, leaving too little free vitamin D for the body to activate and use. This prevents vitamin D levels from rising to the target level, even when patients take the recommended dose.
Most probable mechanism
When vitamin D-binding protein levels are high, it traps most of the vitamin D from supplements, leaving too little free vitamin D for the body to convert into its active form and use for essential functions.
Vitamin D-binding protein is synthesized by the liver and circulates in the blood, binding 85–90% of vitamin D and its metabolites.
In the presence of chronic kidney disease, vitamin D-binding protein levels increase due to altered protein metabolism and compensatory responses to mineral imbalances.
Elevated vitamin D-binding protein binds a larger proportion of orally supplemented cholecalciferol, reducing the concentration of free, unbound vitamin D in circulation.
Reduced free vitamin D limits delivery to the kidneys, where it would normally be converted into its active form, 1,25-dihydroxyvitamin D.
Active 1,25-dihydroxyvitamin D is also tightly bound by vitamin D-binding protein, further reducing its availability to target tissues such as the intestine and bone.
The low bioavailability of free and active vitamin D prevents sufficient activation of vitamin D receptors, resulting in failure to raise serum 25-hydroxyvitamin D above 30 ng/mL despite supplementation.
Evidence from Studies
Supporting (1)
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