In a case report published a few months before my Medical Hypotheses paper — claiming vitamin D is at the heart of the autism epidemic — Drs. Stewart and Latif of the Royal Glamorgan Hospital in South Wales published a case report of a child with autism who also had rickets. However, they failed to connect the dots and did not even discuss the possibility that the vitamin D deficiency had anything to do with the autism.

Stewart C, Latif A. Symptomatic nutritional rickets in a teenager with autistic spectrum disorder. Child Care Health Dev. 2008 Mar;34(2):276-8.

One of the most common questions we receive about vitamin D supplementation is whether to use D2 or D3. Generally, studies show that D3 is more potent and more efficacious, and it is also the “natural” form because it’s what your own body produces.

But let’s look at a recent meta-analysis to settle the potency debate.

Tripkovic L, Lambert H, Hart K, Smith CP, Bucca G, Penson S, Chope G, Hypponen E, Berry J, Vieth R, Lanham-New S. Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis. Am J Clin Nutr. May 2012.

Professor Tripkovic and colleagues at the University of Surrey reviewed 10 randomized controlled trials (RCTs) with a collective total of 1,016 participants ages 18-97. The studies included in the review encompassed a range of different dosages and administration methods:

• Two of the studies administered a single bolus dose of varying quantities, one using alternate routes of administration (oral or intramuscular).
• Six studies preferred daily supplementation with dosages ranging from 1,000 to 4,000 IU.
• One study compared daily to monthly supplementation, 1,600 to 50,000 respectively, while another study supplemented 50,000 IU weekly.
• The final study compared a single intramuscular injection of 300,000 IU of D2 to a single oral dose of 300,000 IU D3.

The researchers found:

• In eight of the studies, regardless of the dose, frequency, or administration, concluded that cholecalciferol (D3) produced a significantly greater increase from baseline serum 25(OH)D levels compared with ergocalciferol (D2).
• Two studies showed D2 and D3 were equally effective.

The authors also determined whether frequency of dosage had an effect on favoring of D2 or D3. Three out of the 4 studies which used bolus doses reported results which favored using vitamin D3 to raise serum levels most effectively. When focusing on the studies which used daily supplementation the results weren’t as strong, but a clear preference for cholecalciferol was present.

So the recommendation remains that D3 is preferable to D2 for better potency. If your doctor prescribes vitamin D from a pharmacy (usually Drisdol), ask them if you might be able to take alternative steps to ensure you receive vitamin D3 instead.

Historians will debate what started the vitamin D era, what paper triggered it, what scientists discovered its remarkable properties, what groups extolled it and what exactly changed people’s mind from initially believing that vitamin D was toxic to believing it was healthy to take 5,000 IU/day. For me the question is easy. In the year 2001, I read a paper that changed my life. It was not even a new discovery or a new finding. Instead, it was a review paper written by Professor Reinhold Vieth of the University of Toronto and published in 1999. It is free to download in its entirety.

Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr. 1999 May;69(5):842-56.

I can remember reading it, thinking, rereading it, and thinking some more, perhaps as many as ten times. Professor Vieth filled the paper with well-established facts. For example, if you go out in the sun naked in the summer around noon and turn slightly pink, you make as much as 20,000 IU of vitamin D.

"Why would nature make such a system that made so much so fast?"

Those facts led me to the simple question of “Why.” Why so much so fast? Why would nature make such a system that made so much so fast? I thought and thought and read and read and the only answer I could come up with was, “Probably for a good reason.” That’s not much of an answer in light of what we know today, but it was good enough to start the Vitamin D Council, and it was good enough to realize that my life’s work was to spread the word. With sickness in the pit of my stomach, I feared that modern medicine had made a terrible mistake in labeling vitamin D toxic, and thus severely limiting the amount in foods and supplements. I also realized that when science makes a great error, great good is waiting around the corner, if someone can correct that error.

Almost every day the answer, “probably for a good reason,” sounds dumber and dumber. We are rapidly finding out the real answers. Every day another scientist publishes a study showing benefits from everything from pediatric cardiomyopathy (infantile heart failure) to hepatitis C to asthma. Nature gives humans such doses of vitamin D from the sun because vitamin D is the only known building block of a potent substance that functions as the “repair and maintenance” steroid hormone of the human body.

However, Vieth’s paper did something else: it convincingly argued that our fear of vitamin D toxicity verged on hysteria and had nothing to do with science. He meticulously researched all the old publications that claimed vitamin D was toxic only to discover a house of cards, papers that referred back to each other and not to any actual scientific papers showing toxicity. That is, he elegantly exposed that 10,000 IU/day could not be toxic (not if we make that much and more from the sun) and that toxicity more likely starts somewhere well above 20,000 IU/day.

I have blogged on telomeres before. Telomeres are the darling of the life extension crowd for a good reason. A telomere is a region at the end of a chromosome that protects it each time the cell divides. Telomeres shorten with each cell replication but help prevent the destruction of the genes at the ends of chromosomes.

Longer telomeres allow the chromosomal ends to shorten with each division without damaging the DNA. As you age, telomeres shorten, so anything that can keep telomeres from shortening too quickly holds hope for improved health.

A finding that vitamin D helps lower blood pressure during winter months has swept headlines all over the world.

United Press International. Vitamin D may help lower blood pressure. April 25, 2012.

We’re here to give you their specific findings!

A research group from Holstebro Hospital in Denmark administered either 3,000 IU/day or placebo to a group of 112 hypertension patients for 20 weeks starting in either October or November. Baseline levels of 25(OH)D were 22.8 ng/ml. After 20 weeks on 3,000 IU/day, the average 25(OH)D level raised to 47.6 ng/ml in the vitamin D group.

This week, Dr. Julian Barth, and colleagues, of the University of Leeds, discovered that vitamin D levels do not decline after a heart attack. At least they do not decline beginning 2 days after the heart attack. This implies vitamin D is not being “used up” or metabolically cleared during the healing of the heart attack.

Barth JH, Field HP, Mather AN, Plein S. Serum 25 hydroxy-vitamin D does not exhibit an acute phase reaction after acute myocardial infarction. Ann Clin Biochem. 2012 Apr 27. [Epub ahead of print]

Dr. Barth studied 48 patients with an acute myocardial infarction (MI) and measured 25(OH)D levels after 2 days, 7 days, 30 days and 90 days post-MI. Inflammation was occurring during this time, as evidenced by rise and fall of CRP, but they found no relationship between CRP and 25(OH)D.

They did not measure vitamin D levels before the heart attack (understandably), so we don’t know if 25(OH)D levels declined from before to after the heart attack (that is, during the acute event). We do know they don’t decline when a damaged heart is healing. Dr. Barth cited a study that found the same thing with an acute malarial infection: vitamin D levels don’t decline during the acute phase of a malaria infection.

(The good news is that people in Leeds are going outside more than during the sun scare. In the winter average 25(OH)D levels were 9.6 ng/ml; in the spring, 15.8; in the summer 30; and in the fall 18 ng/ml, although the numbers were small.)

Compare the lack of metabolic clearance of vitamin D after a heart or malaria attack to what occurs after a knee replacement. Dr. Reid and colleagues of the University of Glasgow found 25(OH)D fell dramatically after a knee replacement. I have reported on this before.

Reid D, Toole BJ, Knox S, Talwar D, Harten J, O’Reilly DS, Blackwell S, Kinsella J, McMillan DC, Wallace AM. 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. Epub 2011 Mar 16.

They measured 25(OH)D before and after a knee replacement on 33 subjects and found 25(OH)D reduced by 40% from before to 2 days after the surgery. Even at three months, 25(OH)D was still 20% lower than preoperative levels indicating, perhaps, the healing knee was “using up” or metabolically clearing the vitamin D. Again, since we don’t know what the 25(OH)D levels were before the MIs in Dr. Barth’s paper, we don’t know if acute MI’s metabolically clear any vitamin D. I suspect they do, although nothing like a knee replacement, which involves major damage to a large joint.

While we only definitively know about the effects of knee replacement surgery on 25(OH)D, I think in the meantime it’s important to be sufficient in vitamin D for lots of reasons when going to the hospital. The take home message is that if you are going into the hospital for any reason, especially surgery, make sure you have plenty of vitamin D reserves by having your 25(OH)D at around 50 ng/ml before admission.

Dr. Gerry Schwalfenberg of the University of Alberta just published the first case report of a woman with a treacherous autoimmune disorder, idiopathic thrombocytopenic purpura or ITP, that vitamin D apparently cured.

Schwalfenberg GK. Solar radiation and vitamin d: mitigating environmental factors in autoimmune disease. J Environ Public Health. 2012;2012:619381.

A paper came out last week that supported, at least to me, the mechanism of action in autism that I proposed in 2007. As you know, some of us are tall, some are short, and science can usually display that and so many other things in nature in some sort of a normal or Gaussian distribution. In what appears to me to be unique research, Dr. Peter Schnatz and his team from Jefferson Medical College wanted to know if some of us have lots of vitamin D receptors (VDR) and some of us only a few. His team also wanted to know if that variation was associated with atherosclerosis.

Schnatz PF, Nudy M, O’Sullivan DM, Jiang X, Cline JM, Kaplan JR, Clarkson TB, Appt SE. The quantification of vitamin D receptors in coronary arteries and their association with atherosclerosis. Maturitas. 2012 Apr 26. [Epub ahead of print]

He took 39 monkeys, kept them out of sunlight and gave them 1,000 IU of vitamin D/day and a plaque building (atherogenic) diet for three years. He then sacrificed them to count the number of VDRs inside their arteries as above the 50th percentile or below, and then measured the height of the atherosclerotic plaque in those arteries. To his surprise a strong negative association exists (p<0.001) between the two.

That is, if you are unlucky enough to be born with only a few VDRs, your atherosclerosis may get bad early, at least according to this animal model. However, he also pointed out that vitamin D itself increases the number of VDRs present. So just taking vitamin D can shift you over to having more VDRS.

This study was of interest to me because it is exactly the mechanism I proposed for the autism epidemic four years ago. In my 2007 paper on autism and vitamin D, I proposed that a quantitative and/or qualitative genetic mechanism was at work in autism. That is, low quantity and/or quality of the inherited vitamin D system have met with declining vitamin D levels over the last 30 years leading to damage to the most sensitive of the vitamin D organs, the developing brain.

Cannell JJ. Autism and vitamin D.Med Hypotheses. 2008;70(4):750-9. Epub 2007 Oct 24

If your genetics deals you low numbers of VDRs and you have to deal with vitamin D deficiency as well, your developing brain loses. The autism geneticists have been looking for mutations. It is not a mutation; the small de novo mutations they do find (in all 23 pairs of chromosomes) are effects, not causes, of autism because vitamin D deficiency impairs DNA repair mechanisms.

Other components of the vitamin D system, such as the amount and activity of the enzyme that makes activated vitamin D, the one-hydroxylase, is also inherited. You get either a little or a lot with most getting somewhere in between, for both quantity and quality, a normal or Gaussian distribution of each. The same is true of the vitamin D breakdown enzyme, the 24-hydroxylase, but here, high amounts are detrimental. More than 70% of your vitamin D level is heritable when levels are low.

Karohl C, Su S, Kumari M, Tangpricha V, Veledar E, Vaccarino V, Raggi P. Heritability and seasonal variability of vitamin D concentrations in male twins. Am J Clin Nutr. 2010 Dec;92(6):1393-8. Epub 2010 Oct 13.

Say you are unlucky enough to inherit low VDRs and low one-hydroxylase enzyme activity both together, and your mother believes in strict sun avoidance and sunblock. She breast feeds you (if mother is below 40 ng/ml, and most are, there is no vitamin D in breast milk) and then weans you on vitamin D-less 100% pure fruit juice and not vitamin D fortified cow’s milk. To boot, you will not eat cold-water fatty fish, reindeer meat, or sea gull eggs (all with some vitamin D). By the time you are 12 months, you literally have no source of vitamin D and your inherited vitamin D physiology will interact with your low vitamin D level to injure your developing brain, as it injures the arteries of monkeys. Exactly the same mechanism can happen in utero.

Presto, you have a brand new “genetic” disease, as autism is, interacting with the environment, as autism is, to create an unfathomable new epidemic, as autism is. While these genetics have always been around, the low amount of substrate is brand new, thus a new “genetic” epidemic. The 1-hydroxylase may be involved because it explains the now 5:1 male to female ratio in autism. Estrogen increases expression of the 1-hydroxylase, but testosterone does not and may inhibit it. In addition, Liel et al reports estrogen does the same to the VDR.

Liel Y, Shany S, Smirnoff P, Schwartz B  Estrogen increases 1,25-dihydroxyvitamin D receptors expression and bioresponse in the rat duodenal mucosa. Endocrinology. 1999 Jan;140(1):280-5.

If I’m right, what do autistic children need? They need enough vitamin D (adult doses) to upregulate their VDRs and their one-hydroxylases in order to stop the autoimmune inflammatory brain damage that is ongoing. If I’m wrong, what will happen? Children will have high-normal vitamin D levels, stronger bones, fewer infections, less asthma, fewer autoimmune disorders, and better physical performance.

Remember, this year, according to the CDC, if you have a male child, he will have a 1 in 54 chance of developing autism by age 8, and the epidemic is growing at almost 20% per year. Couples with an autistic child are under more stress than are couples with a child with a fatal illness. The divorce rate is double. Besides the meltdowns, the parent’s main worry is who is going to care for my child when I’m gone. No person of good heart can ignore this epidemic.

The variation and evolution in skin color and pigmentation are subjects that are still not fully understood or agreed upon. In a recent paper, Professor Nina Jablonski of Penn State University declares, “Skin color has been observed and studied by philosophers and scientists for over two millennia and yet there is still much about it that is not known.” But there are theories.

Jablonski NG. The evolution of human skin colouration and its relevance to health in the modern world. J R Coll Physicians Edinb. 2012 Mar;42(1):58-63.

Any theories regarding skin pigmentation have to consider evolution of both dark pigmentation under high UV radiation (UVR) conditions and evolution of depigmentation under low UV radiation conditions. As we all know, there is a patterned distribution of skin color all over the world, where the lighter your skin color, the further away from the equator your genome evolved.

For the evolution of dark skin pigmentation, there are four major hypotheses proposed to date. They are:

1. Lowered mortality due to protection from sunburn and skin cancer
2. Enhancing survival through camouflage in forested environments
3. The antimicrobial properties of melanin in highly infectious environments
4. Protection of folate metabolism against deficiencies caused by UVR

Jablonski argues that the last theory has the most merit. Folate deficiency interferes with normal development and causes birth defects, thus creating the survival need for adequate folate levels. While folate comes from diet, UVA exposure harms levels of folate’s main serum blood form, 5-methylhydrofolate. Darker pigmentation is able to absorb and scatter UVA and in result, lessen folate destruction. Therefore under high UVR conditions in Africa, it was necessary to have dark skin to maintain folate sufficiency.

On the other hand, there is still the question why skin pigmentation became lighter under low UVR conditions, in places outside the tropics. One theory is that light skin pigmentation evolved to permit easier vitamin D production in the skin.

The less melanin in the skin (lighter skin), the less your skin can “deflect” UVB, allowing your body to more easily produce vitamin D in response to sun exposure. In conditions where there wasn’t as much UVR as the tropics, the body needed to adapt to be able to produce an equal amount of vitamin D, despite having less UVB to work with. And so skin lightened.

This theory is not new, but perhaps gaining more merit now that research is discovering the importance of vitamin D beyond bone health.

In summary, skin pigmentation in modern humans in theory is the result of a dual need to both protect the body from UVR and utilize UVR for vitamin D production. This concept can be applied to sun exposure recommendations. Sun exposure is both beneficial and harmful. There is a dual need to both protect yourself from the sun by avoiding burning, but also expose yourself for vitamin D production.

Professor Heide Cross of the Medical University of Vienna has made major discoveries concerning vitamin D. In particular, she wanted to find ways of increasing the amount of activated vitamin D inside of cells. Working in her lab in Austria, she discovered that several common supplements increase the amount of activated vitamin D inside of cancer cells. They do this by increasing the enzyme that makes activated vitamin D or inhibiting the enzyme that destroys vitamin D.

Those substances, given along with high doses of vitamin D, should increase the amount of activated vitamin D inside of cells, especially cancer cells. Her discoveries may have major clinical applications in cancer and other diseases.