Vitamin D for Disaster Response SummaryVitamin D’s latest findings show this very potent steroid hormone, in high doses, to be a powerful yet safe means to save many lives of those injured in disasters (below is a summary of the full article still in prep)Major new information about this hormone upsets long-held beliefs and describes a much more powerful yet very safe substance.

Use of vitamin D in a large, Level I trauma centerThe largest trauma center in the state of Georgia, Grady Memorial Hospital in Atlanta, did a study in 2009/2010 finding that most patients were deficient in vitamin D and the more deficient they were, the more difficulty and expense they had through surgery and recovery. So they decided to give every patient upon admission 50,000 IU of vitamin D3 and then continued to treat these patients daily with high doses as needed. This reversed the problems of vitamin D deficiency. This is one of the most dramatic examples of the utility of vitamin D3. For example, this large, Level I trauma center has reduced its mortality to close to zero through the use of high-dose vitamin D3. It has also reduced infections, inflammation, the need for ventilators and the need for pain medication. As a consequence, the cost of care has been significantly reduced. No adverse effects of the high-dose vitamin D have been seen. The Director of Critical Care Surgery at Grady, Dr. L.R. Matthews, has found evidence that vitamin D3 dramatically upregulates the immune system response while dramatically downregulating the inflammatory response. [http://goo.gl/o4vT93] [ http://goo.gl/Ajfd8r]

Emory University critical care studyIn May, 2015, Emory University announced results of a randomized controlled trial (RCT) which looked at the effect of high-dose vitamin D3 on the length of hospital stay (LOS) of patients needing critical care. The majority of the patients in the study had severe sepsis or septic shock; while 43 percent had some type of infection upon admission. Some had cardiovascular or neurologic diseases. The 31 patients were divided into 3 groups. One group received a placebo. High doses of vitamin D3 were administered to the other two groups, one receiving 50,000 IU per day for 5 days and the other 100,000 IU per day for 5 days. The LOS of the placebo group was 36 days. For the 50,000 IU/day group it was 25 days, and only 18 days for the 100,000 IU/day group; half that of the placebo group. [http://goo.gl/dMhb2t]

Review of 31 studies of vitamin D status and surgical outcomesThe report of this review stated, “…low perioperative [pre-surgical] vitamin D status is associated with a diversity of adverse outcomes after surgery with statistical significance and clinical importance.” The findings were so dramatic that they concluded, “Practice improvements of comparable potential magnitude with negligible cost and exemplary safety and efficacy are rare, and raise deliberation of the ethical implications of choosing not to test for, and not to treat, low vitamin D status in advance of surgery.” [http://goo.gl/OdnxMB]

Randomized Controlled Trials show cause and effectIt has long been seen in epidemiological/observational studies that people with higher vitamin D levels in their blood are healthier. Such studies have looked at just about every major disease and almost all of them are inversely correlated with vitamin D levels. But doctors want to see cause and effect so they needed results from randomized controlled trials (RCTs). Unfortunately vitamin D has had unexplained mixed results in RCTs. Often, plenty of vitamin D could be seen in blood samples in the form of 25hydroxyvitaminD, best known as 25(OH)D, which is derived in the body from vitamin D and it was thought that this metabolite is what was supplying all of the body’s vitamin D needs. This begged the question, why isn’t the vitamin D working? The only consistently good results were in studies focused on bone health.

Observational studies taught us that adequate blood serum levels of vitamin D for bone health are relatively low compared to that needed for cancer, heart disease and other diseases. When issuing its Recommended Daily Intake (RDI) numbers in November of 2010, the Institute of Medicine (IOM) based them on skeletal needs and not on other factors that would require higher doses. They were troubled by the inconsistency of RCTs for non-bone applications.

The reason that RCTs were failing was that researchers were depending on the wrong vitamin D substance. Dr. Bruce Hollis explained in the October 2013 issue of The Journal of Clinical Endocrinology and Metabolism [http://goo.gl/zweHtx] that what was being measured in the blood, 25(OH)D, was only valuable for bone health. The problem for studies apart from those focused on bone health was that we mistakenly thought the 25(OH)D was available for those other needs.

Vitamin D metabolite 25(OH)DThe original vitamin D we get from the sun/capsules/food is vitamin D3 which is converted by the liver to 25(OH)D. In many RCTs, patients were administered very large bolus (bulk) doses of vitamin D (e.g. 100,000 IU, 300,000 IU) which were meant to last for some weeks to some months.[https://goo.gl/4Ywz4S] This should have been enough given the long half-life of 25(OH)D. We learned only in late-2013 that 25(OH)D does not get used by non-skeletal cells in the body despite them all having vitamin D receptors. Hollis maintains that what they really need is the original

parent vitamin D3 that we get from the sun/capsules/food which hasn’t been converted in the liver to 25(OH)D. The problem has been that while 25(OH)D has a half-life of about 3 weeks, the parent vitamin D has only a 24-hour half-life. Therefore the vitamin D was not there when needed for those RCTs focused on non-skeletal needs. With this understanding, we can now dismiss many of the failed RCTs, giving vitamin D a much higher grade for its ability to provide a large range of benefits without big question marks. However, there have been quite a number of RCTs that have failed due to an inadequate dose level of Vitamin D, often without declaring such a low dose. [https://goo.gl/MiPAEz] Those, too, need to be screened out or clarified.

Vitamin D toxicity is “exceedingly rare”Another concern of doctors was the danger of using too much vitamin D. Many doctors have preferred to prescribe the Institute of Medicine’s (IOM’s) Recommended Daily Intake (RDI) of 600 IU for children older than 1 and adults up to 70 years old. There was the fear that too much vitamin D would raise blood calcium levels too high and that would mainly cause soft tissue and vascular calcification.

We have recently learned from a large, long-term study of vitamin D test results by the Mayo Clinic [http://goo.gl/qEkhf2] that vitamin D toxicity is “exceedingly rare.” This was a ten-year study that looked at over 20,000 blood serum measurements. There was only one that showed a toxic level of calcium. It was a woman who took 50,000 IU of vitamin D daily for more than 3 months and her blood serum level of 25(OH)D was 368 ng/mL. She experienced symptoms of toxic hypercalcemia. Fortunately, people who have become hypercalcemic at such a level with toxic symptoms can simply stop taking the vitamin D and they soon return to normal. The Mayo Clinic study shows that high vitamin D levels (albeit far lower than that of this one woman) and hypercalcemia were not linked. This study outcome is not well-known by doctors as it only first appeared in the May, 2015 issue of the journal Mayo Clinic Proceedings. For further comfort about high doses, the IOM set the No Observed Adverse Effects Level (NOAEL) at 10,000 IU/d, not that adverse effects have been observed at considerably higher intakes.

All-cause mortality studies and vitamin DThese are common studies that look at mortality of a sample population without identifying specific causes. While some all-cause mortality studies have shown the higher your blood serum level of 25(OH)D, the lower the mortality rate, others have shown that after a certain point, the mortality rate creeps back up. The curve is like a U or an inverse J. There are no known specific causes of death from vitamin D except for some very rare cases where people took enormous toxic doses as cited above.

The IOM’s recommended blood serum level of 25(OH)D is 20 ng/mL. Many respected vitamin D experts put the ideal level at 40-50 ng/mL and even higher. Some all-cause mortality studies showed that the adverse effect started as low as in the 30s of ng/mL. Many studies have shown that it is at this level that the benefits of vitamin D are starting to be seen. Dr. Cedric Garland, a highly respected vitamin D researcher at UC San Diego, didn’t believe these results and investigated. He led a meta-study of 32 all-cause mortality studies that used only healthy subjects at the start to remove possible biases. The result was the absence of any sort of U or inverse J curve, about which he wrote, “This is usually related to random variation in the small numbers at the high end of the curve. Due to random fluctuation in a few studies, my colleagues and I don't place too much stock in "U" or inverse J shapes.” He wrote: “I would challenge anybody to show me any example of that; it would be amazing if it were true for vitamin D and very unlikely.” [http://goo.gl/gZ9Dyh]

Concluding commentsAs described, all of the major concerns about vitamin D and the objections of doctors to using high doses have been resolved in recent studies. High doses are safe and effective while the cost of using such high doses is close to zero. For example, a bottle of 100 capsules of 50,000 IU of vitamin D3 can be purchased on Amazon.com for $17.00. There have been a number of studies that show that vitamin D3 is superior to vitamin D2.

There is now enough evidence that vitamin D3 provides major, critical benefits with no significant risk. Hospitals should immediately start considering the use of high-dose vitamin D3 in their trauma centers while first responders should be giving 50,000 IU or more to the injured. If you know that the destination trauma center is not using high-dose vitamin D3 for patients, you could give seriously injured individuals up to 300,000 IU of D3 safely.

While we need to strive towards a level of sufficiency of vitamin D3, we also will benefit from even higher levels as it has been seen in trauma centers that mega-dosing appears to provide almost miracle-like survivability. The doctors at Grady recommend that Americans keep to a year-round blood serum level of at least 50 ng/mL which is best attained by daily supplementation with about 5,000 IU of vitamin D3. There is enough evidence to show that maintaining a high level of vitamin D can help counter disease outbreaks/epidemics/pandemics. People who are deficient in vitamin D will need to take higher doses for several weeks before leveling off at a lower dose.

Much of this information is very new. You will find more about these revelations online. There are very few doctors who are familiar with them so expect to hear conventional remarks from the medical community for now.

Alan D. Roth, Ph.D., (301) 928-6314, alan@alanroth.net – Latest update: October 23, 2015

I am available to talk to groups at length about the value of vitamin D for trauma centers and more.