Special cases
To maintain blood levels of calcium, therapeutic vitamin D doses are sometimes administered (up to 100,000 IU or 2.5 mg daily) to patients who have had their parathyroid glands removed (most commonly kidney dialysis patients who have had tertiary hyperparathyroidism, but also to patients with primary hyperparathyroidism) or with hypoparathyroidism. Patients with chronic liver disease or intestinal malabsorption disorders may also require larger doses of vitamin D (up to 40,000 IU or 1 mg (1000 micrograms) daily). Co-supplementation with vitamin K
The combination of vitamin D and vitamin K supplements has been shown in trials to improve bone quality. As high intake of vitamin D is a cause of raised calcium levels (hypercalcemia), the addition of vitamin K may be beneficial in helping to prevent vascular calcification, particularly in people with chronic kidney disease. Bioavailability
Not all D3 deficiencies can be effectively supplemented or treated with vitamin D3 on its own. Older people or those who have fatty liver or metabolic syndrome have a reduced ability to absorb vitamin D3. In addition, in overweight or obese persons, excessive adipose tissue can sequester D3 from the circulation and reduce its access to other tissues. With age or in obesity, metabolic activation of D3 may be reduced by liver steatosis or by microbiome imbalance.For vitamin D3 to perform its hormonal roles, it is converted into its biologically active metabolite, calcifediol, also known as 25-hydroxyvitamin D3, an activation occurring by a hydroxylation reaction in the liver via the cytochrome P450 system, and in the gut microbiome.
Rickets was formerly a major public health problem among the US population; in Denver, almost two-thirds of 500 children had mild rickets in the late 1920s. An increase in the proportion of animal protein in the 20th-century American diet coupled with increased consumption of milk fortified with relatively small quantities of vitamin D coincided with a dramatic decline in the number of rickets cases. One study of children in a hospital in Uganda, however, showed no significant difference in vitamin D levels of malnourished children compared to non-malnourished children. Because both groups were at risk due to darker skin pigmentation, both groups had vitamin D deficiency. Nutritional status did not appear to play a role in this study. Obesity
There is an increased risk of vitamin D deficiency in people who are considered overweight or obese based on their body mass index (BMI) measurement. The relationship between these conditions is not well understood. There are different factors that could contribute to this relationship, particularly diet and sunlight exposure. Alternatively, vitamin D is fat-soluble, so excess amounts can be stored in fat tissue and used during winter, when sun exposure is limited. Sun exposure
The use of sunscreen with a sun protection factor of 8 can theoretically inhibit more than 95% of vitamin D production in the skin. In practice, however, sunscreen is applied so as to have a negligible effect on vitamin D status. The vitamin D status of those in Australia and New Zealand is unlikely to have been affected by campaigns advocating sunscreen.