Editor Emeritus on July 23rd, 2011

Dr. Cannell answers readers’ questions and sheds light on some of the latest papers on vitamin D.

Dear Dr. Cannell


On Autism

Dear Dr. Cannell:
My son James weighs 48lb, he is 7 yrs old. He had autistic symptoms for almost 5 years (first noticed when he was 2 yrs old). I initially started him on 2,000 IU last November after he caught the flu. Two weeks later, I noticed improvements in areas of social interaction, verbalization. I then increased his dosage to 5,000 IU per your recommendation, and he got better.

His progress has been so great that his kindergarten teacher and Speech Therapist have recommended that he exit the Early Intervention Program.

He is more social, making friends easily, participating in cooperative play, and soon to be in a regular classroom. I think it might be bad luck to say he is cured. Is that possible in a genetic disease? A friend told me he must never have had autism but whatever it was, I don’t want it back. I remember what he was like, and me, too. No thanks.

I’m writing because my son’s pediatrician just called and told me James’s 25(OH) level was 122. He believes he must be toxic because of that level and wants me to stop giving him all vitamin D supplements and recheck his vitamin D level next month. James feels great and shows no signs of toxicity.

What should I do?
Mary, New York

Dear Mary:
That is wonderful news about your son. He is not toxic. However, he should reduce his vitamin D to 2,000 IU/day and recheck his blood level in a month. Some of his symptoms may come back; I don’t know but do not fear, if the symptoms return the vitamin D will take care of them. It appears to me that high dose vitamin D controls, rather than “cures,” some cases of autism. If his level in a month is below 100 ng/ml, the pediatrician will be happy as that is the upper range of normal vitamin D levels.

Yes, autism is a genetic disease, so how can vitamin D treat it? I suspect that one of vitamin D’s many duties in the body is to protect your genome from mutations, organizing the correction of random and point mutations when they occur. Think of your son as having DNA that is unlikely to function properly with lower levels of vitamin D. How long his DNA will be sensitive to low vitamin D, I don’t know.

An immediate question is how much vitamin D to give him now. You want to give him the lowest dose that controls his symptoms. I suspect that he will end up needing 3,000 to 4,000 IU per day to maintain his 25(OH)D around 80-90 ng/ml.

Dear Dr. Cannell:
I just read that someone discovered “geeks” are more likely to have children with autism. I know lots of geeks ‘cause I’m one myself, and it’s scary. I seldom see the sun. Your vitamin D theory of autism fits this geek discovery to a tee. Why can’t other scientists see it?

Andy, Boston

Dear Andy:
One reason is that I’m not a real scientist, I don’t practice science. I read, think, and write. I just came back from speaking for four hours at the American Association for the Advancement of Science (AAAS), and I understand some “real” scientists are upset the AAAS invited me. If I was a real scientist (practiced science, i.e. conducted studies, worked in a lab, etc.) I’d be upset as well. It is just that I saw what scientists did not, in part because my ignorance also meant I had no preconceived notions.

I am afraid that Occam’s Razor is at work here, or “plurality should not be posited without necessity,” which is to say, keep it simple. The autism experts are jumping on and sliding down the razor, theorizing multiple new theories that certain types of minds (math and computer brains) somehow are at more risk for autism. All the autism scientists have to do is stop, open their eyes, and look where the geeks are all day long (inside, out of the sun). It’s that simple. Instead of riding the razor, they need to use Occam’s razor to cut through to the simplest theory. The story below makes it clear that the simplest possibility never crosses their minds.

Andy Coghlan NewScientist 6/20/11 Childhood autism spikes in geek heartlands


Physical Trauma and the Metabolic Clearance of Vitamin D

Dear Dr. Cannell:
Ten days ago, my wife hit a semi-truck trailer t-bone. I know her vitamin D level was 70 ng/ml a week before the accident.  Four days after the accident it was 32.  Are there any studies on major trauma and severe sudden D loss, responses to fight-or-flight mechanisms?

Thanks,
Paul, Minnesota

Dear Paul:
I hope your wife is going to be okay.  While no studies have examined the effect of massive trauma on the metabolic clearance of vitamin D, a recent study showed that having a knee replacement used up tremendous amounts of vitamin D.  It is likely that the trauma of the surgery, and the acute inflammation the surgery caused, was the reason why so much vitamin D was used up.  Be sure your wife gets 50,000 IU of vitamin D every day until she is out of the hospital.

Reid D, et al.  The relation between acute changes in the systemic inflammatory response and plasma 25-hydroxyvitamin D concentrations after elective knee arthroplasty. Am J Clin Nutr. 2011 May;93(5):1006-11.


Vitamin D Blood Serum Levels and Cancer

Dear Dr. Cannell:
I am worried about the studies that show increased risk of cancer with both high and low levels of vitamin D.  What should I do?

Sarah, Maryland

Dear Sarah:
Join the club, especially since a group of good scientists (FNB vitamin D Board) has recently said that vitamin D levels of 50 ng/ml (levels I recommend) may be dangerous. They based their warning on about a dozen studies that show a U-shaped curve, that is, increased risk with both lower and higher vitamin D blood levels. The studies that show this risk are almost all the same type of studies. Scientists take frozen blood samples drawn decades ago and test them for vitamin D in a group of subjects who doctors have followed closely, comparing them to a similar group who did not develop the disease.

However, in a very recent study, a meta-analysis of all such studies done on colon cancer, scientists showed what most studies suggest: there’s a decreased risk with higher vitamin D levels, as the authors put it, “in a linear dose-response manner.” That’s important because it suggests levels of 40 ng/ml are better than levels of 30. However, not enough people have levels high enough to answer the next logical question, “Are levels of 50 better than levels of 40?”

Touvier M et al.  Meta-analyses of vitamin d intake, 25-hydroxyvitamin d status, vitamin d receptor polymorphisms, and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev. 2011 May;20(5):1003-16.

The studies that show a U-shaped risk (increased risk with low and high vitamin D levels) share several similarities. Many, but not all, were conducted in Scandinavian countries, where cod liver oil consumption is high and vitamin A toxicity will run hand in hand with high vitamin D levels. Virtually all were conducted at fairly high latitudes, where a steep fall-off of vitamin D levels occurs in the autumn, a decline that may – according to Professor Reinhold Vieth – cause repeated yearly episodes of intracellular deficiencies of vitamin D. Finally, virtually all the studies share the similarity that scientists measured the vitamin D levels in blood taken during the 1980s and ’90s that had been frozen for at least a decade.

Most, but not all, of the studies in question are cancer studies, especially prostate and pancreatic cancer. If higher vitamin D levels are riskier, then perhaps those who develop cancer will die sooner if their vitamin D levels are high? The exact opposite is true. Studies show that the higher your vitamin D levels at the time of a cancer diagnosis, the longer you live. That is, higher vitamin D levels have a treatment effect in cancer.

Such studies exist for breast, colon, melanoma, lung, and prostate cancers. The higher the vitamin D level at the time of a cancer diagnosis, the longer you live. Similar findings were recently announced for a leukemia that is currently “incurable,” chronic lymphocytic leukemia (CLL). To quote the authors, “”the association between 25(OH)D and survival increased consistently as 25(OH)D increased.” The authors added, “these findings suggest that vitamin D insufficiency may be the first potentially modifiable host factor associated with prognosis in newly diagnosed CLL.” In other words, vitamin D may be the first effective treatment for CLL. Way to go vitamin D!

Shanafelt TD et al. Vitamin D insufficiency and prognosis in chronic lymphocytic leukemia. Blood. 2011 Feb 3;117(5):1492-8.

Please note one other thing. These studies clearly show that people with high vitamin D levels still can get cancer. That is, vitamin D only reduces the risk of getting and dying from cancer; it does not prevent it. This is important because we all know, or will know, someone who took vitamin D and died from cancer anyway. Humans being who they are, friends and relatives of such cancer victims will become dispirited; silently hoping vitamin D is a sure cure. Vitamin D is not that. As I say when I speak, everyone who takes vitamin D will die.


Vitamin D in ICUs

Dear Dr. Cannell:
Why don’t they give vitamin D in the ICU in the hospital? I think they know it will hurt their business.

Jeff, California

Dear Jeff:
When I was young, I always suspected conspiracy. As I grow older, I see that it is usually incompetence. Things are beginning to change. For example, several months ago the journal Critical Care had just the kind of study you are implying the system will not do. They gave 540,000 IU to ten patients near death in an ICU. They gave it via a feeding tube and then compared those patients to ten patients given a placebo. They found that 540,000 IU as a single dose will achieve levels of around 40 ng/ml, but it takes three days to do so (the patients started with levels of around 12 ng/ml).

Amrein K, et al. Short-term effects of high-dose oral vitamin D3 in critically ill vitamin D deficient patients: a randomized, double-blind, placebo-controlled pilot study. Crit Care. 2011 Mar 28;15(2):R104

The overall death rate between the two groups was the same, 50%, but vitamin D patients who still had low blood calcium (common in an ICU) at day three were three times more likely to die than those who obtained normal blood calcium, but the numbers were not large enough for significance. However, the findings suggest that doctors need to give it earlier and give it either intramuscularly or intravenously. Larger doses probably won’t help as the body can’t deal with that much. I predict that eventually vitamin D will be available as an IV and that the most useful preparation will be intravenous 25(OH)D. Oral 25(OH)D was taken off the market several years ago, before the vitamin D revolution began.


The Latest on Vitamin D and Hepatitis C

Dear Dr. Cannell:
I have hepatitis C. Any new studies about vitamin D and hepatitis?

Andy, Florida

Dear Andy:
Last year, scientists announced an exciting development at a liver disease conference: vitamin D helped some people get rid of the infection.

Dan Evan. Haaretz.com Study: Vitamin D could help fight hepatitis C. Already heralded in battling cancer, Vitamin D may also be key to curing hepatitis.

This year a small study showed vitamin D improved the chance that standard treatment, interferon, helped reduce viral loads.

Bitetto D et al. Vitamin D supplementation improves response to antiviral treatment for recurrent hepatitis C. Transpl Int. 2011 Jan;24(1):43-50

My advice: if you have hepatitis, keep your vitamin D levels in the high normal range, 70-90 ng/ml.


Does vitamin D reverse gray hair?

Dear Dr. Cannell:
I want to thank you for your efforts to promote the benefits of vitamin D supplementation. It’s amazing, that the risk factor “vitamin D-deficiency” could so easily, safely and cheaply be treated! But there’s still a lot to do until this fact will be really accepted and realized by the public.

For a few months I have been reading every paper I find about vitamin D and supplementing vitamin D. Since then I hardly had any respiratory infections anymore and much less muscle aches after doing sports!

I also advised my mother to supplement vitamin D and she told me that since then she has less gray hair and the hair is getting colored again!

When I Googled this topic I found many comments and threads of people who had the same experience.

What do you think about it? I’m sure vitamin D helps against gray hair!

It’s really interesting!
Heinrich, Germany

Dear Heinrich:
It would not surprise me as the hair follicle has a vitamin D receptor. However, If it gets rid of gray hair in some people, I’m not one of those people.

John Cannell, MD
Executive Director
Vitamin D Council
1241 Johnson Ave., # 134
San Luis Obispo, CA 93401


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Editor Emeritus on July 22nd, 2011

The US FDA notified healthcare professionals that it is reviewing data from a clinical trial that evaluated the effects of the antiarrhythmic drug Multaq (dronedarone) in patients with permanent atrial fibrillation. The study was stopped early after the data monitoring committee found a two-fold increase in death, as well as two-fold increases in stroke and hospitalization for heart failure in patients receiving Multaq compared to patients taking a placebo. FDA is evaluating whether and how the preliminary results of the PALLAS study apply to patients taking Multaq for paroxysmal or persistent atrial fibrillation or atrial flutter. The PALLAS study results are considered preliminary at this time because the data have not undergone quality assurance procedures and have not been completely adjudicated. FDA will update the public when more information is available.

BACKGROUND: Multaq is approved for use to reduce the risk of cardiovascular hospitalization in patients with paroxysmal or persistent atrial fibrillation (AF) or atrial flutter (AFL), with a recent episode of AF/AFL and associated cardiovascular risk factors, who are in sinus rhythm or who will be cardioverted.

RECOMMENDATION: At this time, patients taking Multaq should talk to their healthcare professional about whether they should continue to take Multaq for non-permanent atrial fibrillation. Patients should not stop taking Multaq without talking to a healthcare professional. Healthcare professionals should not prescribe Multaq to patients with permanent atrial fibrillation. See the Data Summary in the Drug Safety Communication for additional details.

Read the MedWatch safety alert, including a link to the FDA Drug Safety Communication, at:

http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm264204.htm

It seems very unfortunate for the people consuming this drug that the FDA does not know what to do with its “Approved” status! It seems pretty obvious considering that “The study was stopped early after the data monitoring committee found a two-fold increase in death, as well as two-fold increases in stroke and hospitalization for heart failure in patients receiving Multaq compared to patients taking a placebo.” Isn’t it amazing that such gross and alarming findings are only being made now, after the drug is in widespread and totally approved use. How did it ever become approved?

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The US FDA notified the public and the medical imaging community about the potential for inadvertent, increased radiation exposure in patients who underwent or will be undergoing cardiac positron emission tomography (PET) scans with rubidium (Rb)-82 chloride injection from CardioGen-82 manufactured by Bracco Diagnostics, Inc.

A CardioGen-82 PET scan is one of a variety of nuclear medicine scans and uses the radioactive drug Rb-82 chloride injection to evaluate the heart. FDA has received reports of two patients who received more radiation than expected from CardioGen-82. The excess radiation was due to strontium isotopes which may have been inadvertently injected into the patients due to a “strontium breakthrough” problem with CardioGen-82.

RECOMMENDATION: At this time, FDA believes that the risk of harm from this exposure is minimal, although any unnecessary exposure to radiation is undesirable.  The estimated amount of excess radiation the two patients received is similar to that other patients may receive with cumulative exposure to certain other types of heart scans. It would take much more radiation to cause any severe adverse health effects in patients.

Healthcare professionals should closely follow the required testing and quality control procedures essential to help detect strontium breakthrough from CardioGen-82. Other types of heart scans provide information very similar to CardioGen-82 and professionals are encouraged to consider these alternatives while FDA completes its investigation of the reported cases of excess radiation exposure. Patients who have recently had heart scans should talk to their  ealthcare professional if they have any questions. Patients who are planning to undergo a heart scan should talk to the healthcare professional if they are unsure of the type of planned heart scan and the radiation risks associated with the
scan.

Read the complete 2011 MedWatch Safety summary, including links to the Drug Safety Communication, at the FDA here.

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Editor Emeritus on July 15th, 2011

The MedWatch June 2011 Safety Labeling Changes posting includes 50 products with safety labeling changes to the following sections:

  • BOXED WARNINGS,
  • CONTRAINDICATIONS,
  • WARNINGS,
  • PRECAUTIONS,
  • ADVERSE REACTIONS,
  • PATIENT PACKAGE INSERT, and
  • MEDICATION GUIDE.

The “Summary Page” provides a listing of drug names and safety labeling sections revised:

http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm261325.htm

Clicking on a drug product name in the Summary View available via the link above will take you to the “detailed view” page, which identifies safety labeling sections and subsections revised, along with a brief summary of new or modified safety information.

The following drugs had modifications to the BOXED WARNINGS, CONTRAINDICATIONS and WARNINGS sections:

  • Avalide (irbesartan/hydrochlorothiazide) tablets
  • Avodart (dutasteride) soft gelatin capsules
  • Corgard (nadolol) tablets
  • Corzide (nadolol and bendroflumethiazide) tablets
  • Diflucan (fluconazole) tablets, I.V, and oral suspension
  • Diovan (valsartan) tablets
  • Ditropan XL (oxybutynin chloride) tablets
  • Exforge HCT (amlodipine/valsartan/hydrochlorothiazide) tablets
  • Feraheme (ferumoxytol) injection
  • Fioricet with Codeine (butalbital, acetaminophen, caffeine, and codeine phosphate) Capsules
  • Jalyn (dutasteride and tamsulosin) capsules
  • Kenalog-10 (triamcinolone acetonide) injection and Kenalog-40 (triamcinolone acetonide) injection
  • Nexium (esomeprazole magnesium) for delayed-release oral suspension, delayed-release capsules and (esomeprazole sodium) for injection
  • Photofrin (porfimer sodium) for injection
  • Prilosec (omeprazole magnesium) for delayed-release oral suspension and delayed-release capsules
  • Proscar (finasteride) tablets
  • Prozac Pulvules (fluoxetine hydrochloride) capsules for oral use and Prozac Weekly (fluoxetine hydrochloride) delayed-release capsules
  • Renagel (sevelamer hydrochloride) tablets and Renvela (sevelamer carbonate) powder for oral suspension and tablets
  • Simcor (niacin extended-release/simvastatin) tablets
  • Sumavel DosePro (sumatriptan) injection for subcutaneous use
  • Talacen (pentazocine hydrochloride and acetaminophen) tablets
  • Tekturna HCT (aliskiren/hydrochlorothiazide) tablets
  • Torisel (temsirolimus) injection
  • Ultracet (tramadol HCl/acetaminophen) tablets
  • Venofer (iron sucrose) injection
  • Vimovo (naproxen/esomeprazole magnesium) tablets
  • Vytorin (ezetimibe/simvastatin) tablets
  • Zmax (azithromycin extended release) for oral suspension
  • Zocor (simvastatin) tablets

If you are either prescribing or consuming any of the above you would be wise to read the detailed page of information about the changes.

You should avoid taking any drugs unless you absolutely have to take them. Do not be persuaded that you need drugs on the basis of pharmaceutical company advertising! Do not accept a prescription unless the prescriber provides you with a clear explanation of why you need it, how it works, what benefits you should notice, all of the known side-effects, what alternatives exist and what will happen if you decline the prescription.

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Editor Emeritus on July 1st, 2011

We are all waiting for the 900 or so randomized controlled trials that scientists are conducting using vitamin D.  This morning, researchers working at Tufts Medical Center in Boston, under the direction of Professor Anastassios Pittas, published just such a randomized controlled trial in the American Journal of Clinical Nutrition.

Their research group reported that 2,000 IU/day of vitamin D, given for 12 weeks, significantly improved pancreatic function in mildly overweight adults with pre-diabetes. Unfortunately, the lead author, Dr. Joanna Mitri, did not comment on the low dose of vitamin D they used, 2,000 IU/day, which only increased vitamin D levels from 24 to 30 ng/ml. Nor, in spite of it being a randomized controlled trial, did the authors make any new clinical recommendations for the people who paid for their study, the citizens of the United States.

In spite of the low dose and short length of their study, they found their principal outcome, a measurement of pancreatic function, increased by 300 in the vitamin D group but fell by 126 in the placebo group. I cannot link the study to PubMed as it is not yet listed there; it will be in a few days.

Joanna Mitri, Bess Dawson-Hughes, Frank B Hu, and Anastassios G Pittas.  Effects of vitamin D and calcium supplementation on pancreatic b cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized controlled trial. AJCN. First published ahead of print June 29, 2011 as doi: 10.3945/ajcn.111.011684.

In the end, they studied 22 volunteers in the vitamin D group and 22 in the placebo group. However, to give you an idea of what a feat this study was, how difficult it was to get enough subjects, they started with 911 subjects yet ended up randomizing only 44 into the vitamin D study. They did a parallel calcium study with 45 subjects, which found calcium had no benefit on pancreatic function.

The same senior author, Professor Anastassios Pittas, recently announced the results of a much larger epidemiological study that showed for every 5 ng/mL increase in vitamin D levels, the risk of developing diabetes dropped by 8%.  However, he was quick to warn that such epidemiological studies should not change clinical recommendations, only randomized controlled trials can do that. Then, when he oversees just such a randomized trial, not a word of clinical advice, only the ever-present request for more research money from the citizens of this country.

http://diabetes.webmd.com/news/20110628/study-vitamin-d-may-cut-risk-of-diabetes

Of course the Food and Nutrition Board will say they never said levels greater than 20 ng/ml had no added benefits, only that no good evidence existed for such a benefit at the time they issued their report. Actually, if you exclude the science of epidemiology, that is still a false statement. The point is that history will record that someone was wrong.  Maybe it will be me and the Vitamin D Council’s recommendation, going into its fifth year, that adults should take at least 5,000 IU per day.  Or maybe it will be Professor A. Catharine Ross, of Penn­sylvania State University, the chairwoman of the recent FNB that concluded 600 IU/day is the Recommended Daily Allowance, all adults need.  Looking at the study published today, it is clear that 600 IU/day would not have resulted in a significant improvement in pancreatic function.

I predict that after most of the randomized controlled trials are out – in another ten years – the FNB will meet again and say “whoops,” it should have been 5,000 IU/day all along. However, by then the premature death count will be in the millions.

John Cannell, MD
Vitamin D Council

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