Baltimore, Maryland, USA: Johns Hopkins researchers have found that lower than normal blood levels of vitamin D were linked to increased risk of early signs of interstitial lung disease (ILD). Interstitial lung disease is a relatively rare group of disorders characterized by lung scarring and inflammation that may lead to progressive, disabling and irreversible lung damage.
An estimated 200,000 cases a year are diagnosed in the United States, most of them caused by environmental toxins such as asbestos or coal dust, but it can be caused by autoimmune disorders, infections, medication side effects or, sometimes, from unknown causes. Once diagnosed with the disease, most people don’t live longer than five years. In a series of studies, the researchers sought to learn about new, and potentially treatable, factors related to early signs of the disease seen by CT scans — imaging abnormalities that may be present long before symptoms develop — which may help guide future preventive strategies.
Results of the most recent data analysis, published in the Journal of Nutrition on June 19, suggest that low vitamin D might be one factor involved in developing interstitial lung disease.
The researchers reviewed medical information gathered on more than 6,000 adults over a 10-year period,
Although the researchers caution their results can’t prove a cause and effect, their data support the need for future studies to investigate whether treatment of vitamin D deficiency, such as with supplements or sunlight exposure, could potentially prevent or slow the progression of the disorder in those at risk. Currently, there is no proven treatment or cure once interstitial lung disease is established.
“We knew that the activated vitamin D hormone has anti-inflammatory properties and helps regulate the immune system, which goes awry in ILD,” says Erin Michos, M.D., M.H.S., associate professor of medicine at the Johns Hopkins University School of Medicine and associate director of preventive cardiology at the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease. “There was also evidence in the literature that vitamin D plays a role in obstructive lung diseases such as asthma and COPD, and we now found that the association exists with this scarring form of lung disease too.”
To search for that association, Michos and her research team used data from the Multi-Ethnic Study of Atherosclerosis (MESA), which from 2000 to 2002 recruited 6,814 people from Forsyth County, North Carolina; New York City; Baltimore, Maryland; St. Paul, Minnesota; Chicago, Illinois; and Los Angeles, California. The average age of participants was 62, and 53 percent were women. Thirty-eight percent of participants were white, 28 percent were African-American, 22 percent were Hispanic and 12 percent were Chinese.
At an initial clinical visit, staff took blood samples for each participant and measured, among other things, vitamin D levels. Those with vitamin D levels less than 20 nanograms per milliliter — about 30 percent of participants — were considered vitamin D deficient (2,051 people). Those with vitamin D levels of 20–30 nanograms per milliliter were considered to have “intermediate,” although not optimal, levels of the nutrient, while those with 30 nanograms per milliliter or more were considered to have met recommended levels.
All participants underwent heart CT scans at the first visit and some also at later visits, offering incidental and partial views of the lungs.
At 10 years in, 2,668 participants had full lung CT scans evaluated by a radiologist for presence of scar tissue or other abnormalities.
The vitamin D-deficient participants had a larger volume, on average (about 2.7 centimeters cubed), of bright spots in the lung suggestive of damaged lung tissue, compared with those with adequate vitamin D levels. These differences were seen after adjusting for age and lifestyle risk factors of lung disease including current smoking status, pack years of smoking, physical inactivity or obesity.
When looking at the data from the full lung scans, the researchers said those with deficient or intermediate vitamin D levels were also 50 to 60 percent more likely to have abnormalities on their full lung scans suggestive of early signs of interstitial lung disease, compared with those with optimal vitamin D levels.
These associations were still seen after additionally adjusting for other cardiovascular and inflammatory risk factors, such as high blood pressure, high cholesterol, diabetes and levels of high-sensitivity C-reactive protein (another inflammatory marker).
“Our study suggests that adequate levels of vitamin D may be important for lung health. We might now consider adding vitamin D deficiency to the list of factors involved in disease processes, along with the known ILD risk factors such as environmental toxins and smoking,” says Michos. “However, more research is needed to determine whether optimizing blood vitamin D levels can prevent or slow progression of this lung disease.”
People can boost their vitamin D levels by spending 15 minutes a day in summer sunlight or through a diet that includes fatty fish and fortified dairy products. Supplements may be considered for some people with significant deficiency.
According to the 2013 Global Burden of Disease study, about 595,000 people worldwide develop interstitial lung disease each year, and about 491,000 die each year from it.
Additional authors include Samuel Kim, Di Zhao and Eliseo Guallar of Johns Hopkins; Anna Podolanczuk, R. Graham Barr and David Lederer of Columbia University Medical Center; Pamela Lutsey of University of Minnesota, Minneapolis; Steven Kawut of University of Pennsylvania; and Ian de Boer and Bryan Kestenbaum of University of Washington.
The study was funded by grants from the National Institute on Neurological Disorders and Stroke (R01NS072243), the National Heart, Lung, and Blood Institute (R01HL096875, R01HL077612, R01HL093081, RC1HL100543, R01HL103676, T32HL105323 and K24HL131937) and the National Center for Advancing Translational Sciences (UL1TR000040, UL1TR001079 and UL1TR001420), as well as contracts from the National Heart, Lung, and Blood Institute (HHSN2682015400003I, N01HC95159, N01HC95160, N01HC95161, N01HC95162, N01HC95163, N01HC95164, N01HC95165, N01HC95166, N01HC95167, N01HC95168 and N01HC95169), funds from the Blumenthal Scholars Fund for Preventive Cardiology and a research assistance agreement from the U.S. Environmental Protection Agency (RD831697).
Michos received an honorarium from Siemens Healthcare Diagnostics in 2016; de Boer has consulted for Medtronic and received equipment and supplies from Abbott for work outside this study. Lederer has consulted for Roche, Veracyte, Philips Respironics, FibroGen, Global Blood Therapeutics, Sanofi Genzyme and ImmuneWorks.
If I get enough Vitamin D, do I need the supplements?
Vitamin D appears to be a wonder vitamin in regard to health. For whatever ails you, it seems, vitamin D is the cure.
Vitamin D is so crucial for healthy bones that deficiencies in children lead to the malformed bones seen in rickets. Because vitamin D helps the body absorb calcium, it’s vital for a host of other biological functions as well. In fact, vitamin D acts more like a hormone in that way.
The recommended daily allowance of Vitamin D is 600-800 units. It can be found in foods fortified with vitamin D – and the numbers of those products seem to be increasing – or from fatty fish or eggs. But the majority of the vitamin D that our bodies need begins with UVB light; our bodies use this light to produce the precursors of vitamin D.
Adults who are out in the sun regularly, and have normal vitamin D levels, probably don’t need a vitamin D supplement. A meta-analysis published in the renowned medical journal The Lancet reviewed 24 studies that followed patients who took vitamin D. The research found little change in bone density with supplementation of vitamin D. Some studies found that vitamin D reduced the risk of bone fracture – but only when it was combined with calcium.
Calcium on its own has been shown repeatedly to decrease the risk of fractures. Vitamin D on its own has not been shown to decrease fracture risk.
Some practitioners recommend mega-doses of vitamin D to their patients, causing very high blood levels of vitamin D. But high levels of vitamin D in the bloodstream might actually increase the rate of bone breakdown.
The highest daily intake considered safe by the Institute for Medicine is 4,000 units. If you are taking vitamin D, have your blood levels checked. For the prevention of osteoporosis, the Institute of Medicine recommends a vitamin D blood level greater than 20 ng/mL. The majority of people can achieve this level without supplementation, but if you do supplement, 600 units is more than sufficient.
As for all the other purported health benefits of vitamin D, such as its ability to decrease the risk of cancer and heart attacks, there may be benefit to vitamin D intake, but we’re not sure yet. We need good long-term studies that compare people who take vitamin D daily against those who don’t.
Until then, if you don’t have osteoporosis and you do have sufficient vitamin D levels in your blood, there appears to be little additional benefit to taking a vitamin D supplement.
Vitamin D3, Not D2, Is Key to Tackling Vitamin D Deficiency
Vitamin D3 is significantly more effective at raising the serum biological marker of vitamin D status than vitamin D2 when given at standard doses in everyday food and drink, say UK researchers — findings that could have major implications for both current guidelines and the supplement industry.
In a randomized controlled trial of vitamin D supplements, vitamin D3, which is derived from animal products, was associated with significantly higher serum total 25-hydroxyvitamin D [25(OH)D] levels after 12 weeks than vitamin D2, which is plant-based and currently used in the vast majority of vitamin D supplements.
The research was published in the American Journal of Clinical Nutrition.
“The importance of vitamin D in our bodies is not to be underestimated, but living in the UK it is very difficult to get sufficient levels from its natural source, the sun, so we know it has to be supplemented through our diet,” explained lead author Laura Tripkovic, PhD, department of nutritional sciences, University of Surrey, Guildford, United Kingdom, in a press release.
She added, “Our findings show that vitamin D3 is twice as effective as D2 in raising vitamin D levels in the body, which turns current thinking about the two types of vitamin D on its head.”
“Those who consume D3 through fish, eggs, or vitamin D3-containing supplements are twice as likely to raise their vitamin D status [compared with those] consuming vitamin D2-rich foods, such as mushrooms, vitamin D2-fortified bread, or vitamin D2-containing supplements, helping to improve their long-term health.”
Senior researcher Susan Lanham-New, PhD, head of the department of nutritional sciences at the University of Surrey, added: “This is a very exciting discovery that will revolutionize how the health and retail sector views vitamin D.”
“Vitamin D deficiency is a serious matter, but this will help people make a more informed choice about what they can eat or drink to raise their levels through their diet.”
Approached for comment, Robyn Lucas, MD, PhD, College of Medicine, Biology and Environment, Australian National University, Canberra, told Medscape Medical News: “I do think that this study really does show that vitamin D2 doesn’t raise total 25(OH)D levels as effectively as vitamin D3.”
“Clearly that has implications for any food fortification,” she added, stressing that all vitamin D supplements in Australia are vitamin D3-based.
Dr Lucas continued, “Personally, I think the evidence suggests that it is only quite severe vitamin D deficiency that is problematic for health, so levels below, say, 30 nmol/L. In Australia, those levels are uncommon because we have so much sun.”
“A higher proportion of the UK population will be in that category and should think about supplementation. This study shows that quite a modest dose of vitamin D3 was sufficient to raise levels well above 50 nmol/L. So it is also useful in showing that you really don’t need big doses to achieve and maintain sufficient levels of 25(OH)D.”
Current Guidelines State D3 and D2 Are Equivalent
Current guidelines by the US National Institutes of Health, UK Department of Health, and various other government bodies state that vitamins D2 and D3 are equivalent and achieve the same effect. However, emerging evidence suggests that vitamin D3 may be more effective in increasing serum total 25(OH)D levels.
Dr Tripkovic and colleagues therefore conducted a randomized, double-blind, placebo-controlled fortification trial in which 335 South-Asian and white European women aged 20 to 64 years were assigned to placebo or one of four groups:
Placebo juice with placebo biscuit (placebo, n = 65).
Juice supplemented with 15-µg vitamin D2 with placebo biscuit (D2J).
Placebo juice with biscuit supplemented with 15-µg vitamin D2 (D2B).
Juice supplemented with 15-µg vitamin D3 with placebo biscuit (D3J).
Placebo juice with biscuit supplemented with 15-µg vitamin D3 (D3B).
The treatments were given daily for 12 weeks, and 59 placebo patients completed the study, alongside 60 D2J patients, 58 D2B patients, 59 D3J patients, and 55 D3B patients. All patients who started the study were included in the analysis, however, on an intention-to-treat basis.
Combining the two ethnic groups, researchers found that the placebo group experienced a 25% reduction in serum total 25(OH)D levels over the 12-week intervention, a mean absolute change of -11.2 nmol/L (P < .0001).
In contrast, the D2J and D2B groups saw increases in total 25(OH)D levels of 33% and 34%, respectively, while increases in the D3J and D3B groups were 75% and 74%, respectively.
Furthermore, the D3J group showed significantly higher increases in serum total 25(OH)D levels vs the D2J (16.9 nmol/L, P < .0005), D2B (16.0 nmol/L, P < .0003) and placebo (42.9 nmol/L, P < .0005) arms.
The D3B group was also associated with significantly higher increases in serum total 25(OH)D levels vs the D2B (15.2 nmol/L, P < .0003), D2J (16.3 nmol/L, P < .0005) and placebo (42.3 nmol/L, P < .0003) groups.
There were no significant differences between the D3B and D3J groups over the course of the intervention, and there were no significant interactions for ethnicity. However, South-Asian women appeared to have a greater response to both vitamin D2 and D3 than European women, which researchers ascribed to their lower baseline total 25(OH)D levels.
Findings May Also Help in Quest for Vitamin D to Reduce Diseases
Dr Tripkovic told Medscape Medical News that, in addition to potentially shaking up the supplement industry, their findings may help in the quest to link vitamin D supplementation to measurable clinical outcomes.
She said, “If other researchers want to understand the health benefits of vitamin D, with a hard outcome like bone health or cardiovascular disease…shoring up things like what we know about vitamin D is really important so that those who then take the research forward to look at health outcomes have a sound evidence base to design their study on.”
The next steps required in terms of research to take the concept of food fortification forward include casting the net wider to determine which other foods containing vitamin D3 will be effective — as well as acceptable — to the general population, she said.
Moreover, Dr Tripkovic would like see more dose-response data to obtain a better sense of the lower end of the dose spectrum.
“We gave 600 IU, which was basically benchmarked against the American recommendation because, at the time we were drawing together the study, the UK didn’t have a recommendation for vitamin D,” she explained.
“Now the UK has come out with 10 µg/day, which is 400 IU.”
She summarized, “So, it’s understanding the lower doses, and it’s understanding how food fortification can work with vitamin D in the population. It’s bigger numbers, basically.”
“The fact that we’ve managed to pull a lot of women out of deficiency over the wintertime has been really incredible to see and it’s very exciting, so we’re very hopeful, for the future, that we can keep getting research funding and carry on with our work,” she concluded.
What About Bioavailability of Different Forms of Vitamin D?
One issue this study does not address, said Dr Lucas, is the question of whether 25(OH)D derived from vitamin D2 [25(OH)D2] is less bioactive than 25(OH)D3.
“The challenge here is knowing what the outcome might be against which to measure bioactivity. It is the same problem that we have in being able to measure how much 25(OH)D is ‘sufficient,’ and hence the arguments about what level of 25(OH)D we should aim for.”
“This is probably the most important outstanding question, but I’m not sure that it is going to be able to be answered,” she said.
The second study was supported by the UK-based Biotechnology and Biological Sciences Research Council (BBSRC) as part of a BBSRC Diet and Health Research Industry Club grant. Dr Lanham-New is research director for D3Tex Ltd, which holds the UK patent (with Gulf Corporation Council patent pending) for the use of any UV-B material for the prevention of vitamin D deficiency in women who dress for cultural style. The other authors have reported no relevant financial relationships.