Johns Hopkins researchers have found that lower than normal blood levels of vitamin D are linked to increased risk of early signs of interstitial lung disease - 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.
About 595,000 people worldwide develop interstitial lung disease each year, and about 491,000 die each year from it, according to the 2013 Global Burden of Disease study. 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.
The researchers sought to learn about new, and potentially treatable, factors related to early signs of the disease seen by CT scans. The imaging abnormalities that may be present long before symptoms develop may help guide future preventive strategies.
The results were published in the Journal of Nutrition and 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 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, which from 2000 to 2002 recruited 6,814 people.
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.
Boosting Vitamin D Levels
The researchers took blood samples for each participant and measured vitamin D levels. Those with vitamin D levels less than 20 nanograms per milliliter were considered vitamin D deficient - about 30 percent. Those with vitamin D levels of 20 to 30 nanograms per milliliter were considered to have “intermediate,” although not optimal, levels of the nutrient.
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.
Ten years later 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 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, years of smoking, physical inactivity or obesity.
The data from the full lung scans revealed 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.
“Our study suggests that adequate levels of vitamin D may be important for lung health,” Michos said. “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. However, more research is needed to determine whether optimizing blood vitamin D levels can prevent or slow progression of this lung disease.”
Vitamin D And Dementia
New research from South Australian scientists in the science journal Nutritional Neuroscience shows that vitamin D is unlikely to protect individuals from multiple sclerosis, Parkinson’s disease, Alzheimer’s disease or other brain-related disorders.
The findings reported that researchers had failed to find solid clinical evidence for vitamin D as a protective neurological agent. “Our work counters an emerging belief held in some quarters suggesting that higher levels of vitamin D can impact positively on brain health,” says lead author Krystal Iacopetta, Ph.D. candidate at the University of Adelaide.
Iacopetta investigated the role of vitamin D across a wide range of neurodegenerative diseases based on a systematic review of over 70 pre-clinical and clinical studies. “Past studies had found that patients with a neurodegenerative disease tended to have lower levels of vitamin D compared to healthy members of the population,” she says.
“This led to the hypothesis that increasing vitamin D levels, either through more UV and sun exposure or by taking vitamin D supplements, could potentially have a positive impact. A widely held community belief is that these supplements could reduce the risk of developing brain-related disorders or limit their progression.”
“The results of our in-depth review and an analysis of all the scientific literature however, indicates that this is not the case and that there is no convincing evidence supporting vitamin D as a protective agent for the brain,” she says.
She believes that the idea of vitamin D as a neuro-related protector has gained traction based on observational studies as opposed to evaluation of all the clinical evidence.
“Our analysis of methodologies, sample sizes, and effects on treatment and control groups shows that the link between vitamin D and brain disorders is likely to be associative as opposed to a directly causal relationship,” she said. “We could not establish a clear role for a neuroprotective benefit from vitamin D for any of the diseases we investigated.”
Miracle Sunshine Tablet
“This outcome is important and is based on an extremely comprehensive review and analysis of current data and relevant scientific publications,” added Professor Mark Hutchinson, Director of the ARC Centre of Excellence for Nanoscale BioPhotonics and Professor at the University of Adelaide who worked with Iacopetta on the research and findings. “We’ve broken a commonly held belief that vitamin D resulting from sun exposure is good for your brain.”
Hutchinson said that there may be evidence that sun exposure could impact the brain beneficially in ways other than that related to levels of vitamin D. “There are some early studies that suggest that UV exposure could have a positive impact on some neurological disorders such as multiple sclerosis,” he said.
“We have presented critical evidence that UV light may impact molecular processes in the brain in a manner that has absolutely nothing to do with vitamin D. We need to complete far more research in this area to fully understand what’s happening. It may be that sensible and safe sun exposure is good for the brain and that there are new and exciting factors at play that we have yet to identify and measure. Unfortunately however, it appears as if vitamin D, although essential for healthy living, is not going to be the miracle ‘sunshine tablet’ solution for brain-disorders that some were actively hoping for.”
Link Between Low Vitamin K And The Heart
A recent study - published in The Journal of Nutrition - of 766 otherwise healthy adolescents shows that those who consumed the least vitamin K1- found in spinach, cabbage, iceberg lettuce and olive oil - were at 3.3 times greater risk for an unhealthy enlargement of the major pumping chamber of their heart. Vitamin K1 – also known as phylloquinone - is the predominant form of vitamin K in the U.S. diet.
"Those who consumed less had more risk," says Dr. Norman Pollock, bone biologist at the Georgia Prevention Institute at the Medical College of Georgia at Augusta University and the study's corresponding author.
The scientists believe theirs is the first study exploring associations between vitamin K and heart structure and function in young people. About 10 percent of the teens had some degree of this left ventricular hypertrophy. Left ventricular changes are more typically associated with adults whose hearts have been working too hard, too long to get blood out to the body because of sustained, elevated blood pressure.
Unlike other muscles, a larger heart can become inefficient and ineffective. While more work is needed, their findings suggest that early interventions to ensure young people are getting adequate vitamin K1 could improve cardiovascular development and reduce future disease risk.
The study found that for the 14 to 18 year olds who consumed the least vitamin K1 the overall size and wall thickness of the left ventricle were already significantly greater and the amount of blood the heart pumped out significantly lower. Changes were independent of other factors known to influence heart structure and function, including sex, race, body composition, physical activity and blood pressure.
Only 25 percent of the teens in the study met current adequate intake levels of the Food and Nutrition Board of the Institute of Medicine, says Mary Ellen Fain, MCG second-year student and the study's co-first author. "They had higher levels relative to the other kids," Fain said. "But even at that age, it seemed to make a difference in their hearts."
It was clear that none of the participants consumed large amounts of the vitamin. Vitamin K is known to be important to blood clotting and healthy bones. There is increasing evidence of its cardiovascular impact as well. One direct, negative impact of low vitamin K intake on the heart may be reduced activity of matrix Gla protein, which helps prevent calcium deposits on blood vessel walls.
Like matrix Gla protein, vitamin K is essential to increased production of osteocalcin, a protein hormone important to bone metabolism and insulin sensitivity. Those parallels and the fact that osteocalcin can't currently be given directly led Pollock to pursue his ongoing clinical trial in obese children with higher-fasting glucose levels.
Pollock's lab and other investigators in the United States and Europe are also looking at the impact of vitamin K supplements on adults with heart disease, but adult findings to date have been inconclusive. Further study is needed to clarify the importance of vitamin K1 intake to cardiovascular development and to better understand how vitamin K-dependent proteins, like matrix Gla protein, aid cardiovascular development and health, the scientists note.
Participants wore activity monitors for seven days and completed between three and seven 24-hour periods of self-reports about what they ate. About 70 percent had a least six days of food records, which increases the accuracy of self-reports.
The Framingham Offspring Cohort Study found an association between higher vitamin K1 levels and higher levels of the good LDL cholesterol and lower lipid levels in the blood, both associated with healthier hearts. Adult studies, like the Nurses' Health Study and Prospective Army Coronary Calcium study, have provided conflicting evidence of its cardiovascular impact. The short-acting vitamin is active only about six hours after it's consumed.
Dairy Products And Vitamin K
Recent research from scientists at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University sheds new light on the vitamin and its significant presence in some dairy products available in the United States.
In the study, published in Current Developments in Nutrition, researchers quantified the activity of two natural forms of vitamin K in dairy products of various fat contents and found that common U.S. dairy items, including milks, yogurts and cheeses, contain appreciable amounts of multiple forms of vitamin K. Vitamin concentrations varied by fat content.
Dietary sources of vitamin K are found in two natural forms: phylloquinone - PK, or vitamin K1 - which is widely distributed through plant-based foods, and menaquinones - MK, or vitamin K2 - which appear to be primarily in animal products and fermented foods.
Almost all MK forms are also produced by germs in the human gut. Not much is known about MK amounts in U.S. dairy products. “Dairy foods contain minute amounts of PK, the best known of the vitamin K forms, and so dairy is not commonly considered a rich dietary source for this nutrient,” says Xueyan Fu, Ph.D., first and corresponding author and scientist in the Vitamin K Laboratory at the USDA HNRCA.
“However, when it comes to MK forms, we found that dairy items already found in many peoples’ refrigerators are indeed a good dietary source for vitamin K.”
Guidelines for adequate vitamin K intake are based only on PK intake without consideration for other forms of vitamin K. MK differ from PK in structure in that they are compounds with different numbers of isoprenoid units in the side chain, designated as MK4 through MK13.
Which forms of MK are present reflects which germs might be in the dairy products. Lactic acid germs, for example, are widely used in dairy and fermented foods. To understand the presence of MK and PK in dairy products, the researchers used 50 nationally collected dairy samples provided by the USDA Nutrient Data Laboratory and 148 dairy samples purchased in 2016 from Boston area retail outlets.
The products were divided into categories based on dairy types and fat content - milks, yogurts, Greek yogurts, kefirs, creams, processed cheeses, fresh cheeses, blue cheeses, soft cheeses, semi-soft cheeses, and hard cheeses.
The effect of fat content on total vitamin K in all forms was compared using a two-sample T-test. The vitamin K content of cream products, for which the researchers had a smaller sample size, was analyzed using a general linear model, with heavy cream as the reference group.
All full-fat dairy products contained appreciable amounts of MK, primarily in the forms of MK9, MK10 and MK11. Combined, these three forms of MK accounted for approximately 90 percent of total vitamin K present in the foods tested. In cheeses, the total vitamin K content varied by type, with soft cheese having the highest concentration, followed by blue cheese, semi-soft cheese, and hard cheese. All of the cheeses contained MK9, MK10 and MK11, and modest amounts of PK, MK4, MK7, MK8 and MK12. Little MK5, MK6 or MK13 was measured in the majority of cheeses.
The vitamin K concentrations in milk varied by fat content. Total vitamin K and individual MK concentrations in full-fat milk were significantly higher than in 2 percent milk. PK was only detected in full-fat milk. Only MK9-11 were detected in milk. In yogurts, full-fat regular and Greek yogurts exhibited similar vitamin K concentrations as in full-fat milk. Neither MK nor PK were detected in fat-free yogurt.
“Estimated intakes of PK and MK in dairy-producing countries in Western Europe suggest that between 10 and 25 percent of total vitamin K intake are provided by MK, and primarily from dairy sources,” added Sarah L. Booth, Ph.D., last author on the study. “Additionally, observational data from Europe suggest that MK from dairy products have a stronger association with heart health benefits compared with PK intakes. This data from other countries highlights the need to analyze MK in commonly consumed foods in the U.S.”
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