In the popular imagination, vitamin D is a milk supplement included for bone health. But its benefits go way beyond the skeleton. A multi-year University of Colorado study on nursing home and assisted living residents has added strong evidence of vitamin D’s positive influence on the immune system, particularly among those with vitamin D deficiency. For many patients, that “D” might as well stand for “defense.”
Adit Ginde, MD, MPH, a University of Colorado Hospital Emergency Department physician and professor and vice chair for Research in the CU Department of Emergency Medicine, focuses his scientific work on the link between vitamin D and lung infection among older patients. In November, he and colleagues reported that, among seniors of an average age of 81 who live in metro Denver long-term care facilities (LTCs), high doses of vitamin D reduced acute lung infections by an astonishing 40 percent over a 12-month period.
Ginde cautions that the study was small – 107 patients in total, 55 of them receiving high doses of vitamin D averaging out to about five times the USDA’s recommended daily dose of 600-800 international units (IUs). But it’s more proof that vitamin D supplements among the aged can help them fight off illnesses such as pneumonia, influenza and bronchitis as well as other sorts of infections, which are, Ginde said, “important and common problems in this population.”
Robert Schwartz, MD, division head for the CU School of Medicine’s Department of Geriatric Medicine and a co-author of the study, explains why. Respiratory infections typically mean a few missed workdays through middle age, he says. “But in this population, if you have obstructive pulmonary disease, or heart disease, or renal disease, or all of the above, adding yet another stressor – even though it’s generally a mild stressor for healthy people – can tip you over.”
It would take a major clinical trial with hundreds or thousands of patients to prove Ginde’s study’s findings definitively, he said. But the results of such a trial would be years away, assuming it launched at all, which it hasn’t. Until then, Ginde said, the balance of evidence suggests that adding regular vitamin D supplements to seniors’ pill boxes could be a very good idea.
Why it works
Vitamin D is not in fact a vitamin, but a type of hormone produced naturally by the skin when exposed to the sun. It chaperones calcium into bones (avoiding rickets among children and osteoporosis among older adults) and, it’s become clear only recently, plays a vital role in the immune system’s ability to fight off infection.
Sunlight has long been part of lung-disease care: tuberculosis patients flocked to sanatoriums in sunny places such as Colorado, and patients were urged to get outside. By 2006, scientists at UCLA had untangled the biochemical process behind the long-apparent anecdotal association of vitamin D with enhanced infection-fighting ability. (As with about everything in immunology, it’s complicated, but boils down to vitamin D being a key part of a chain of events unleashing a potent antimicrobial peptide.)
That work was done by looking at how human immune system cells responded to added vitamin D. Ginde’s team looked at humans themselves – in particular, seniors.
“My broad interest is in patients with acute infection,” Ginde said. “In our population in the Emergency Department and among the patients we need to hospitalize in the ICU, older patients are clearly at much higher risk.”
Schwartz said vitamin D’s role as an infection-fighter is still unfamiliar even to physicians working with older patients.
“I don’t think a lot of people in geriatrics think about vitamin D for its immunological importance,” he said. “We think about it for muscle and bone. We know that there are a significant portion of older people who are either vitamin D insufficient or deficient.”
Vitamin D deficiency is exacerbated by a vicious circle. Older patients, and especially sick ones, spend less time in the sun, driving down their natural vitamin D production when they need it most.
The National Institutes of Health and American Geriatrics Society-funded study, launched in 2011, turned out to be quite a challenge. For one thing, despite having excluded patients with a terminal diagnosis, the cohort’s age and ill health led to about 20 percent of those who signed up dying during the study period.
Patients in long-term-care facilities are at higher risk of acute lung infection than those living independently – hence Ginde’s focus there. Schwartz added that nursing home patients also represented a distillation of both vitamin D deficiency and lung-infection prevalence. That combination, the researchers felt, could shed light on the proposed vitamin D-lung infection connection more clearly and efficiently than a larger study of random people might. Plus the payoff could be big, Schwartz said: “Nursing home patients are expensive to care for and are hospitalized a lot.”
Ginde figured that the residents at perhaps eight LTCs would suffice for the 150 patients the study targeted. But the American Geriatrics Society made the study it was funding harder to carry out when it released its consensus statement on vitamin D for the prevention of falls. The statement recommended doses of about 4,000 IUs per day. That might be a good thing for the geriatric population, Ginde said, but it put many prospective patients over the 1,000 IU-per-day upper bound for inclusion in the study. Ginde and colleagues ended up reaching out to 25 LTCs and still only managed to land two-thirds of its intended cohort.
The team wrestled with challenges including very sick patients, regulatory hurdles, and other challenges that have foiled many attempts at nursing-home studies, which are, as Schwartz put it, “really difficult to pull off.”
This meant even more running around for study coordinators Keith Breese, MA, and Lida Zarrabi, MA. Because the LTCs couldn’t officially participate in the study, their staff couldn’t dispense vitamin D to patients. So Breese, Zarrabi, or temps and students working with them had to personally offer each patient his or her vitamin D capsule over the course of the year.
Falls a side effect?
The many constraints introduced a wrinkle in the study: rather than taking a daily pill, participants took a single, big dose once a month. Those in the high-dose group got 100,000 IUs; the rest received either a monthly placebo (if their vitamin D intake was up to recommended daily allowance standards) or 12,000 IUs (if they were taking less than RDA standards suggested).
That big monthly dose may have been responsible for the study’s most notable side effect: those taking the big vitamin D doses had more falls, a finding that two other vitamin D studies had also found. Still, other factors may have been at play, Ginde said. The high-vitamin-D cohort included a disproportionate number of “frequent fallers” – people who fell more before the vitamin D regimen took effect, and for which Ginde and colleagues hadn’t controlled for up-front (this had been, after all, an infection study, and not a fall study). Given the study’s small sample size, had two or three frequent-fallers been assigned to a different group, the effect could have largely gone away, Ginde said.
In addition, Ginde said, despite research demonstrating that vitamin D improves muscle function and balance among the elderly, it could be that, because people were feeling better thanks to the vitamin D, they moved around more and, as a result, fell more, too. What’s important to recognize, he said, is that all three of the studies associating vitamin D with falls involved big, intermittent doses of vitamin D, which isn’t how people typically take supplements or produce their own vitamin D in real life.
“Because people I treat have trouble remembering to take things once a week or once a month, I give it to them every day in the pill box,” Schwartz said.
He added that the study, in which he served mainly as a sounding board to Ginde, was “exceedingly well-done,” and one that doctors treating vitamin D-deficient patients – geriatric or otherwise – would be wise to note.
Ginde is moving ahead with his vitamin D research. In February 2017 he will lead the launch of a 3,000-patient trial across 50 U.S. hospitals. The idea is to screen for vitamin D deficiency in emergency department patients being admitted to the ICU and, for those who need it, give them a single, large dose (540,000 IUs) and see how it affects 90-day survival.
“I personally think there’s strong support for vitamin D in the infection realm,” Ginde said. “But the onus is on science to prove that this works.”