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Newsletter: Vitamin D studies of interest

Posted on: September 15, 2009   by  John Cannell, MD


This month I will try a different format for the newsletter, the references are linked to the headline. Most of the studies or articles reviewed below are brand new, published this month or last, a few are older.

For whatever reason, the national press has reduced reporting on new Vitamin D studies, so I will try to cover a few of the more remarkable papers published in the last six weeks.

Vitamin D and H1N1 Swine Flu

So far, Swine flu, H1N1, has killed thirty-six children in U.S. and analysis of CDC data indicates vitamin D deficient children at higher risk of death

I’m not sure I can do this, watch our children die this winter from what may be a preventable disease, influenza, I’m not sure I’m strong enough. A few minutes ago, the CDC issued a report on Swine flu deaths among children; 36 U.S. children dead so far this season and the season hasn’t started yet. The dead children were much more likely to be Vitamin D deficient; but the CDC did not realize they discovered this. However, anyone familiar with the Vitamin D literature will recognize it.

The clue: almost two-thirds of our dead children had epilepsy, cerebral palsy, or other neurodevelopmental conditions like mental retardation. What do we know of these neurological conditions? All are associated with childhood Vitamin D deficiency; I won’t bore you with the references but anyone who has ever cared for these children knows it; anyone who has studied these diseases on Medline knows it; anyone who has one of these kids knows it; these kids just don’t go in the sun very much. If they do live at home and go outside, parents use sunblock because the child is so vulnerable, never robust. In addition to sunlight deprivation, many of these kids take anticonvulsant drugs, which lower Vitamin D levels.

One more thing, 36 dead kids before the flu season has even started alarms me. In the last 4 years, around 100 kids died per year from influenza; this year the toll is 36 and the flu season has not yet begun.

Swine Flu Sends More Blacks, Hispanics to Hospital

The above racial differences apply to hospitalization rates for H1N1 in Boston and Chicago. It looks as if Vitamin D is a big factor in H1N1. During the 1918–1919 pandemic, Blacks actually had lower illness rates, not higher, perhaps because they had antibodies from previous H1N1 infection in 1916 and 1917. It worried me to read that the 1918 H1N1 was circulating in the world for several years before it devastated that same world in 1918–1919. The same could be true now, that is, this H1N1 may be relatively benign (only kill 50,000 Americans/year) for several years, infect more Blacks than whites, then erupt into a merciless killer in 2011, when Blacks will be relatively protected because of their higher antibodies from higher infection rates in 2009 and 2010.

American Children Vitamin D Deficient

Most American teenagers are Vitamin D deficient and low levels in teenagers are associated with teenage hypertension, obesity, and metabolic syndrome

Researchers at Johns Hopkins and the NIH (led by Dr. Jared Reis) looked at 3500 American teenagers and found teenagers with the lowest Vitamin D levels, compared to the highest, were 5 times more likely to be obese, 2.5 times more likely to be hypertensive, 2.5 times more likely to have elevated blood sugar, and about 4 times more likely to have the metabolic syndrome. Only 25% of the teenagers had levels higher than 26 ng/mL while 25% had levels lower than 15 ng/mL.

What upset me the most about this study was that the authors did not conclude teenage Vitamin D deficiency should be treated; they concluded scientists should be given more money to study the deficient teenagers: “Additional research is necessary…” and “evidence from randomized controlled trials is required before Vitamin D supplementation can be recommended…” One fourth of American teenagers with levels less than 15 ng/mL and Dr. Reis, the NIH, and Johns Hopkins doesn’t think anything should be done but give scientists more money? Email Dr. Reis and tell him what you think: reisjp@nhibi.nih.gov.

58 million American children are Vitamin D deficient; 7.6 million are severely deficient and nobody is doing anything about it

Dr. Jahi Kumar and colleagues at Albert Einstein School of Medicine looked at more than 6,000 American kids (age one to 21) who were carefully selected to be representative of the average American child. 9% of the kids had 25(OH)D levels less than 15 ng/mL and 70% (representing 58 million kids) had levels less than 30 ng/mL. The older, blacker, or heavier the child, the more TV and video games, the higher the chance the child is deficient. Tragically, 59% of black teenage girls had levels less than 15 ng/mL.

Children with low levels were more likely to have abnormal blood lipids, high blood pressure, obesity, and abnormally elevate parathyroid hormone levels, all risks for future cardiovascular disease. Only 4% of American children take recommended doses of Vitamin D supplements, surely a failure of U.S. pediatricians.

German and British Children, Vitamin D and Long Ago

From 1955 to 1990, all infants in East Germany received 600,000 IU of Vitamin D every three months for a total of 3,600,000 IU at age 18 months

With the 400 IU/day recommendation of the American Pediatric Association in mind, I ran across this amazing paper while surfing Medline for Vitamin D. According to this paper, all infants in the German Democratic Republic (East Germany) received dangerously high doses of Vitamin D every three months in their doctor’s office. The policy was in place for 35 years. The first 600,000 IU dose was given at three months and then every three months until the child was 18 months of age. This works out to an average of 6,000 IU per day (actually, for several technical reasons it is not equivalent) for 18 months. The authors collected blood before the dose and then 2 weeks after the quarterly dose to obtain 25(OH)D, 1,25(OH)2D, and calcium levels on a total of 43 infants.

Before the first dose, at 3 months of age, the average infant was extremely deficient (median 25(OH)D of 7 ng/mL). Two weeks after the first dose the average 25(OH)D level was 120 ng/mL, the second dose, 170 ng/mL, the third dose, 180 ng/mL, the fourth dose, 144 ng/mL, the fifth dose, 110 ng/mL and after the sixth and final dose, 3.6 million total units, at age 18 months, the children had mean levels of 100 ng/mL. That is, by the 15 and 18 month doses, the children were beginning to effectively handle these massive doses.

The highest level recorded in any of the 43 infants was 408 ng/mL at age 9 months, two weeks after the third 600,000 IU dose. 34% of the infants had at least one episode of hypercalcemia but only 3 had an elevated serum 1,25(OH)2D. The authors reported that “all the infants appeared healthy,” even the infant with a level of 408 ng/mL, that is, no clinical toxicity was noted in any of these infants.

They also reported that “repeated inquires in GDR have failed to identify clinical Vitamin D toxicity as a result of the prophylactic program.” The pediatricians and health officials in the GDR just did not look hard enough for toxicity as such doses will certainly cause clinical toxicity, right? Or maybe such doses only cause asymptomatic hypercalcemia and not clinical toxicity. It would be interesting to look at the infant mortality in East Germany during those years, compared to similar Eastern European countries, as well as current cohorts of German adults who underwent such treatment as an infant.

Two years after Great Britain halved its Vitamin D dose for infants, due to the “Great Vitamin D Panic,” the incidence of infantile hypercalcemia was unchanged.

Fifty years ago, Great Britain laid the foundation for every subsequent U.S. Food and Nutrition Board (FNB) Vitamin D recommendation when England had a fit of hysteria, the “Great Vitamin D Panic.” Professor Bruce Hollis wrote about this scare in some detail in a 2004 paper, and how the British panic affected the American FNB. He also details the role the Williams syndrome played in the “Great Vitamin D Panic.” Williams syndrome is a genetic malformation that causes, among other things, infantile hypersensitivity to Vitamin D, elevated 1,25 levels even without supplemental Vitamin D, and often hypercalcemia in response to supplemental Vitamin D. (In fact, it was by studying the Williams Syndrome that I became more convinced of the relationship of Vitamin D to autism. Kids with the Williams syndrome, the only human disease with greatly elevated serum 1,25 levels around birth, grow up to have an adult personality that is the phenotypic opposite of autism, thus they are an experiment of nature.)

Anyway, in the midst of the panic, Great Britain reduced infant supplementation by one-half in 1957, expecting to see a reduction in infantile hypercalcemia (7.2 cases per month in the country). It did not. Two years later, in 1959, the incidence of infantile hypercalcemia in Great Britain was essentially unchanged (6.8 cases per month.) However, by 1961, the reported incidence was apparently halved to 3 cases per month. The British Paediatric Association concluded “it remains speculative whether the decrease in hypercalcemia by 1961 is a consequence of reduced Vitamin D intake” because it was “not chronologically related to the reduction of Vitamin D intakes introduced in 1957.”

It seems likely that what happened was this. The “Great Vitamin D Panic” began in the early 1950s and British pediatricians began drawing lots of blood calcium levels on their infant patients, fearful they were toxic. They kept drawing frequent blood calcium levels and thus detecting high baseline blood calcium levels until 1960 when the “Great Vitamin D Scare” ebbed and they drew fewer and fewer infantile blood calcium levels. Thus fewer high baseline levels were detected and, by 1961, fewer British infants diagnosed with high blood calcium. It was simply due to fewer blood tests ordered for calcium; it had nothing to do with Vitamin D.

Vitamin D and Infant, Children’s Health

Low Vitamin D levels associated with increased disease severity in childhood Systemic Lupus Erythematosus (SLE)

Childhood SLE is a tragic disease, one of the autoimmune diseases that have risen to epidemic levels in our children in the last 20 years. Afflicted children develop debilitating kidney, joint, bone, heart, blood, and lung disease; almost all require immunosuppressants (prednisone and hydroxychloroquine) to ward off looming debilitation and death.

Dr. Tracey Wright and colleagues at the University of Texas Southwestern Medical Center found severe Vitamin D deficiency was 5 times more common in SLE children than in controls (37% vs. 9%), that a measure of SLE disease severity was 2.5 times higher in SLE children with Vitamin D deficiency, that 78% of SLE children who were prescribed Vitamin D were still severely deficient (that is, their pediatricians were prescribing insignificant amounts of Vitamin D while telling them— correctly in the case of SLE—to avoid the sun), and serum activated vitamin D levels (calcitriol) were significantly lower in SLE kids than healthy controls. (Tragically, the true believers of the Marshall Protocol—and I know no scientists who are—recommend these children get even less Vitamin D.) The authors concluded, “Vitamin D deficiency may be a modifiable risk factor for morbidity in SLE and represents a target for intervention.”

Vitamin D deficient mothers with HIV are more likely to infect their baby

Dr. Saurabh Mehta and colleagues at Harvard discovered higher Vitamin D levels in HIV infected mothers helped prevent fetal death and HIV transmission to the infant. At 24 months of age, toddlers from low maternal 25(OH)D HIV mothers had a 46% increased risk of acquiring HIV and a 61% increased risk of dying. The authors found an insignificant but disturbing trend for increased infection and mortality in mothers with 25(OH)D levels greater than 70 ng/mL but not enough mothers had such levels to draw any conclusions.

Vitamin D appears to be involved in a rapidly increasing number of infections, from influenza, tuberculosis, bacterial vaginitis, sepsis, the common cold, and now to HIV. When are scientists going to get around to looking at the wintertime killer and crippler of kids, meningitis?

More evidence Vitamin D deficiency is involved in infantile cardiomyopathy

Dr. Jennifer Brown and colleagues at Children’s National Medical Center reported on four more babies with life-threatening cardiomyopathy (when the heart swells up and cannot pump blood effectively). All four babies improved dramatically with Vitamin D treatment, including three babies who are now off all cardiac medications (I hope that does not include Vitamin D, which is a crucial cardiac medicine.) and one infant who was taken off the heart transplant list after treatment with Vitamin D.

The problem with the paper was that the authors only looked at infants whose Vitamin D levels were so low that their body could not maintain their blood calcium levels and also had rickets. The authors concluded the cause of the cardiomyopathy in the four infants was low serum calcium. I emailed Dr. Christopher Spurney, the senior author, reminding him that Vitamin D has direct effects on heart muscle cells, above and beyond its effects on calcium, and that he should check Vitamin D levels on all infants with cardiomyopathy and treat those with a low levels, not just rachitic or hypocalcemic infants. He replied that the Children’s National Medical Center is now doing just that.

Vitamin D Levels

How do statins work? They dramatically raise vitamin D levels

Several studies have shown that statins raise 25(OH)D levels but last month this study showed that Crestor nearly tripled Vitamin D levels, from 14 to 36 ng/mL, in just 8 weeks. I loved what the author concluded, “We have no idea of the mechanism involved.” Nor do I, as statins should lower, not increase, vitamin D levels because statins reduce Vitamin D’s precursor, cholesterol. As Dr. Yavuz said, “This is clearly an opportunity for further research.”

These results are simply amazing, from 14 to 36 ng/mL in 8 weeks and the study was conducted in the winter, when levels should fall, not rise. Just think, if the pleiotropic (many effects) statin drugs work by simply raising Vitamin D levels (and statins’ pleitropic effects are certainly not mediated through lowering cholesterol levels), then that is one expensive way to raise Vitamin D levels. However, it is the perfect commentary on the American health care system; that is, in America we use statins to treat Vitamin D deficiency, not Vitamin D.

Widely fluctuating levels of Vitamin D, due to summer sun exposure and winter sunlight deprivation, may be harmful

Professor Reinhold Vieth of the University of Toronto, has produced evidence that widely fluctuating levels of Vitamin D in patients with low baseline 25(OH)D levels may increase the risk of prostate and pancreatic cancer. At least two prostate cancer studies and two pancreatic cancer studies show that higher baseline 25(OH)D levels at latitudes far from the equator increase, not decrease, the risk of these two malignancies. Vieth produces evidence that this increased risk is related to widely fluctuating levels 25(OH)D in those who rely on summer sun exposure for their Vitamin D.

The latency of the intracellular enzymes that activate and destroy Vitamin D explains why Vitamin D should be obtained on a regular basis and not in periodic high doses. When 25(OH)D levels fall abruptly, like in the autumn in countries far from the equator, the enzyme that makes activated Vitamin D inside the cell is still set on low and the enzyme that destroys activated Vitamin D is still set on high and it takes several weeks or even months to fully reset. Vieth believes any supplementation strategy that uses large doses at longer than two month intervals should be avoided. However, high or “Stoss” doses, such as 50,000 IU of D3 every week or two should pose no problem. Vitamin D2, or ergocalciferol (Drisdol) should be avoided as it causes wider 25(OH)D fluctuations than D3 does.

Vitamin D Testing

American Association of Clinical Chemists: Vitamin D Testing—What’s the Right Answer?

College of American Pathologists: Vitamin D intrigues, but not a done deal

In the above two reports, what really caught my eye above was at the Cleveland Clinic, Vitamin D blood tests jumped from 1,500 tests a month in 2006 to 12,000 a month in 2009. Cleveland Clinic switched to DiaSorin Liaison method to keep up with the demand. That tells me no matter what the Food and Nutrition Board does, patients and doctors are catching on: Vitamin D deficiency is best treated.

If you want to know about the problems with Vitamin D blood testing, read the above two articles. However, my recommendation is not to read them. It will just upset and confuse you. Even if you are a doctor, maybe especially if you are a doctor, don’t read them. You expect lab tests to be accurate, give the same result with the same blood sample. Well, okay, believe that if you want.

Robert Michel, publisher of the Dark Report, just reported on his latest experience with Vitamin D testing. The results are not good, especially for Quest Diagnostics. Michel sent 24 aliquots, or identical samples, of his blood, all drawn the same day, to two different reference labs, which in turn sent them, over a three week period, for 24 Vitamin D blood tests. Again, 24 blood samples, drawn from the same person at the same time, so, in a perfect world, all 24 samples would test the same.

However, the results varied from 36 ng/mL to 66 ng/mL! Quest’s results: 36, 42, 51, 54, 55, and 66. The Mayo Clinic, which uses the same technique that Quest uses, did better, 48, 48, 51, and 61. The good news was the immunoassay methods used by LabCorp, Clinical Pathology Labs, and ARUP clustered around 44 ng/mL and all 11 samples were within 4 points of 44 ng/mL with the highest 48 and the lowest 39.6.

Long story short, if you use Quest Diagnostics, divide by 1.3 and hope they continue to work at improving their process. Mayo’s is better but Dr. Singh must be getting tired of all those Vitamin D tests, which are hard to do on mass spec. If your lab sends out to LabCorp, ARUP, or Clinical Pathology Labs, you are fine.

If you use ZRT, know that it is a mass spec technique; it has to be mass spec to be done on a blood spot. ZRT is also harmonized to the gold standard, that is, corrected to the gold standard. By gold standard I mean the method that the scientific studies use when they study cancer, heart disease, autoimmune disease, etc. When you see an article that says a new study showed higher Vitamin D levels are associated with longer life, etc., that study almost always used DiaSorin RIA, the gold standard, or DiaSorin Liaison, which gives almost identical results to the DiaSorin RIA.

I see that Dr. Graham Carter, a great proponent of accurate Vitamin D testing, slammed me and ZRT in a recent paper in Clinical Chemistry.

Carter GD. 25-Hydroxyvitamin D assays: the quest for accuracy. Clin Chem. 2009 Jul;55(7):1300–2.

Graham is angry, perhaps, because it was not his watchdog organization, DEQAS, that first detected the problem with inaccurate Vitamin D testing at Quest? Instead, he admits, it was the Vitamin D Council who first blew the whistle on Quest Diagnostics.

Dr. Carter said, correctly, that ZRT home testing “cannot easily be monitored by external proficiency testing schemes.” Graham is right, schemes, such as Graham’s DEQAS, cannot easily monitor home testing by ZRT, because ZRT uses blood on a blotter paper and not serum. ZRT may be able to be modified to participate in DEQAS, if ZRT can afford it, ZRT is a small lab. I’ll ask ZRT if they can find a way to participate.

For those who do not know, this is what DEQAS does. Participating commercial labs pay DEQAS a fee (that is not disclosed on their website but reportedly substantial) so DEQAS will check that lab’s precision. DEQAS then sends participating labs batches of standardized Vitamin D samples. In other words, it seems that the major reference labs keep DEQAS in business.

The problem with DEQAS is they refuse to send the test samples blind, like Robert Michel did for the Dark Report. In reality, the commercial labs all recognize the DEQAS batches when they come in the mail and all the commercial labs run their DEQAS samples very very carefully. The best DEQAS can hope for is to find out if commercial labs can do it right, not if they do it right.

In the best of all possible worlds, all commercial Vitamin D testing would be accurate, patients would not have to seek in-home Vitamin D levels because their physicians would already have done so in the office, and everybody could afford commercial lab fees, which can range up to $200.00 per test. In the best of all possible worlds, if doctors did order a Vitamin D test, they would order the correct test and finally, in the best of all possible worlds, doctors would know how to correctly interpret the tests that they ordered.

Until then, if you have health insurance or can afford it, I recommend using LabCorp, ARUP, Clinical Pathology Labs, or Cleveland Clinic. If you use the home Vitamin D test kit from ZRT, they have already corrected for the DiaSorin RIA/mass spec uniform variance but realize it is a mass spec technique. ZRT also submitted, at my request, samples for comparison with RIA and they were quite accurate. Plus, I review ZRT’s results; I know they are not artificially high; in fact, way too many of ZRT results are incredibly low. Falsely elevated results is where the danger lies, thinking you are fine when you are deficient.

Treating Vitamin D Toxicity

Vitamin D toxicity presents with weight loss, malaise and fatigue, followed by anorexia nausea and vomiting, and patients so afflicted almost always have increased thirst, increased urination, and nighttime urination

Ever heard of 50,000 IU tablets of Ertron, or Deltalin or Davitin, or Dalsol? You may have if you went to doctor in the 1930s and 1940s. Some doctors of that time prescribed the above drugs, all of which were Vitamin D2, now prescribed as Drisdol. Apparently, some doctors of the time believed massive D2 doses helped arthritis.

This 1948 paper from Johns Hopkins is remarkable for the dosage the doctors prescribed for arthritis and for the toxicity those doses sometimes caused. In their series of 10 toxic patients, the dose ranged from a low to 150,000 IU/day to a high of 600,000 IU/day and it took anywhere from 2 to 18 months for these daily doses to cause clinical toxicity. Clinical toxicity was manifested by weight loss, malaise and fatigue, followed by anorexia, nausea and vomiting. (Note, if you have these symptoms you are not vitamin D toxic, unless you have been taking at least 50,000 IU per day for many months, which is definitely not recommended.)

All toxic patients in the above paper had high blood calcium—anywhere from 12.4 to 15 mg/dL—and 9 of 10 were anemic; all had evidence of kidney impairment. The two bone biopsies were both normal. Seven of the ten patients insisted their arthritis was improved by Vitamin D toxicity and most complained their arthritis returned several months after withdrawal of Vitamin D, return of said arthritic complaints coincided closely with the return to normal of blood calcium.

Treatment of toxicity was simple, stop the Vitamin D. None of the life-threatening corticosteroid treatment toxic patients are given today. Simply stop the Vitamin D, keep them out of the sun, have them drink 4 liters of water a day, and wait. The clinical symptoms disappear in several weeks. The blood calcium returns to normal in several months. Most patients continued to show evidence of some renal damage but that damage appeared to be improving over time. Unlike modern corticosteroid treatment of Vitamin D toxicity, nobody died.

Vitamin D Meetings

The second meeting of the new Vitamin D Food and Nutrition Board (FNB) held in Washington DC on August 4, 2009

If you scroll down on the above link you can listen to dozens of presentations at the recent FNB on Vitamin D and the talks range from “more is urgently needed,” to “nothing should change until scientists get a lot more money,” to “Vitamin D is poison.” Of course it is poison, as Paracelsus said, “All things are poison, and nothing is without poison, only the dose permits something not to be poison.” The readers of this newsletter will remember that vitamin D is used as a rat poison. I love the fact that the U.S. government recommends Americans take a rat poison every day, but they do not recommend enough rat poison.

What will the new Food and Nutrition Board do? What doses will they recommend? All you have to do is listen to the presentations; this FNB may not do very much. I hope I’m wrong. At the very least, I hope they raise the Upper Limit, as that may allow research to be done using the correct dose.

If they stick to the current dangerously low daily adequate intake (AI) 200 IU/day recommendations, it will injure pregnant women and their newborn children the most. The reason: the average person will not take a vitamin supplement, but virtually all pregnant women will take one, a prenatal vitamin. If the FNB increases the AI for pregnancy above 400 IU/day, the prenatal vitamin manufacturers will quickly increase the D content of prenatal vitamins, which is now at a meaningless 400 IU per tablet. The good news is that word is spreading; people are talking, telling friends and neighbors how much Vitamin D
helps. I know this because Vitamin D blood testing is skyrocketing.

14th Vitamin D Workshop in Brugge, Belgium, October 4th to 8th

If you are a scientist, do not miss this workshop. If you are a lay person, read the program before you register.

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