The study, published in the current Mayo Clinic Proceedings, found the percentage of participants with vitamin D levels greater than the current upper safe concentration cut-off of 50 ng/mL rose significantly over the course of 10 years, but the rates of vitamin D toxicity and hypercalcemia remained exceedingly rare.
In particular, the researchers, led by Daniel Dudenkov with the Department of Internal Medicine at Mayo Clinic, found that from 2002 to 2011 there was a 26-fold increase in the number of participants who had vitamin D levels higher than 50 ng/mL. In addition, of the 1,714 subjects, 0.6% had concentrations higher than or equal to 80 gn/mL and 0.2% had levels equal to or exceeding 100 ng/mL.
This increase most likely is attributable to increased vitamin D supplementation related to rising awareness of vitamin D deficiency, the authors note.
Despite the higher vitamin D levels, the incidence of vitamin D toxicity did not rise. Rather, only four – or 0.2% – of the participants with vitamin D levels higher than 50 ng/mL “were associated temporally with hypercalcemia,” the most common symptom of vitamin D toxicity, according to the study. Of these, only one person had clinical toxicity, and that person had a vitamin D level of 364 ng/mL.
The research further downplays the other three cases of mild hypercalcemia, which were found in participants with vitamin D levels between 51 ng/mL and 100 ng/mL, by noting the patients had no clinical symptoms and no associated low parathyroid hormone levels, which would be expected.
Thus, the researchers conclude, vitamin D levels are unlikely to cause harm up to 100 ng/mL, which is twice the concentration recommended by IoM and aligns with the Endocrine Society’s guidelines for the treatment and prevention of vitamin D deficiency.
Safe but unnecessary?
Even though the finding supports the safety of 10,000 IU of vitamin D daily, which corresponds with a concentration of 100 ng/mL, the researchers stop short of endorsing the Endocrine Society’s recommendations.
They note that even though levels higher than 100 ng/mL are safe, they have not been proven helpful – especially for the general population. They also echo the concerns IoM voiced when setting the upper limit for vitamin D in 2011, which related to research showing vitamin D levels greater than 30-60 ng/mL were associated with increased risks of all-cause mortality, heart disease, cancers and falls and fractures.
Good news and good timing
While the researchers may be unwilling to take a strong stance favoring the Endocrine Society’s recommendations, the study should give dietitians and health care practitioners greater confidence recommending doses of vitamin D of 1,000 to 2,000 IU daily for healthy people and 3,000 to 4,000 IU for those deficient in the vitamin without fear of risk, said Duffy MacKay, senior VP of scientific and regulatory affairs at the Council for Responsible Nutrition.
He also noted that while the study was too late to influence the IoM’s recommendation, it is “good news and good timing” for the ongoing discussion about the upcoming 2015 dietary guidelines. By underscoring the low risk of intake, the study could influence language around fortification and supplementation, he said.
It also is well timed with FDA’s revision of nutrition labels, which will include vitamin D to help people better understand if they are consuming enough of the vitamin, MacKay said.
By focusing on the safety of extremely high levels of vitamin D, the study falls short as a tool for addressing whether lower but consistent supplementation is helping to adequately address vitamin D deficiency concerns, MacKay said.
“It would have been interesting to see the number of people who were moderately deficient with low but normal levels of vitamin D in the teens and 20s who moved into the 30s and 40s,” MacKay said. “That would have indicated if we are doing the right thing and moving people from suboptimal levels to optimal levels.”
To have that data, the study would have needed to compare how many people had vitamin D levels equal or greater than 20 ng/mL, 30 ng/mL and 40 ng/mL in addition to its measurements at 50 ng/mL, 80 ng/mL and 100 ng/mL.
The study also did not indicate whether the concentration levels were changing because patients’ were self-administering vitamin D or if they were prescribed large doses, Michael Holick, a medical doctor with the Department of Medicine at Boston University Medical Center, notes in an editorial published with the study.
Other research, however, suggest dangerously excessive vitamin D levels may come from prescribed high doses, usually in the range of 50,000 to 100,000 IUs daily for several months, he said.
However, because high-dose vitamin D supplements also are available without a prescription, the researchers conclude that health providers should pay closer attention to the doses of non-prescription vitamin D use by patients.