Updated clinical vitamin D guidelines

Michael Holick, MD, Ph.D., told me in a phone interview nearly a year ago that vitamin D insufficiency and deficiency was "one of the most common medical conditions" and has implications on the health of bones, the heart, the immune system, and likely every cell in the body.

Dr. Holick added, "If a normal adult isn’t taking at least 1,500 to 2,000 IU from supplement and diet—and you can’t really get it from your diet—then we know you’re vitamin D deficient."

Now, The Endocrine Society has released new clinical practice guidelines intended to help curtail widespread vitamin D deficiency with extra focus on care for populations who are most at risk.

The guidelines follow on the coattails of last November's updated vitamin D recommendations by the Institute of Medicine (IOM), which several experts have condemned as conservative and inadequate. In response, a "Task Force," led by Dr. Holick, reexamined the evidence and compiled new recommendations to provide a more therapeutic emphasis.

The guidelines call for screening populations at risk for vitamin D deficiency and correcting deficiencies with supplementation at levels high enough to maximize effects on calcium, bone and muscle metabolism.

The Task Force recommends maintaining blood concentrations of 25(OH)2D (the active circulating form of vitamin D) consistently above 30 ng/mL. Circulating blood levels below 30 ng/mL are regarded as "insufficient" and below 20 ng/mL as "deficient".

To assist at-risk individuals with meeting blood levels above 30 ng/mL of circulating vitamin D, the Task Force issued new dietary intake recommendations that differ significantly from those given by the IOM:

• Infants ages 0-1: 400-1,000 IU/day
• Children ages 1-18: 600-1,000 IU/day
• Adults ages 18+: 1,500-2,000 IU/day
• Pregnant or nursing women under 18: 600-1,000 IU/day
• Pregnant or nursing women 18+: 1,500-2,000 IU/day
• Obese children and adults: at least 2-3 times the recommendation for their age group
• Children and adults on anticonvulsants, antifungals and AIDS medications: at least 2-3 times the recommendation for their age group

The Task Force also increased Tolerable Upper Limits for vitamin D to substantially higher levels than what the IOM recommended last fall.


In addition, they recommend higher dosages of vitamin D as clinical strategies for patients with vitamin D deficiency, malabsorbtion syndromes, and patients on medications that may affect vitamin D metabolism. Patients with these conditions should work with their personal physicians to determine what dosage is right for them.

Acknowledging a gap in the clinical evidence, the Task Force suggested that more trials with higher intakes of vitamin D are "desperately needed" to more properly understand the potential health outcomes.

During an online news conference, Dr. Holick asserted that 30ng/mL should only be regarded as a minimum for maintaining a healthy body. The ideal range for circulating blood levels of vitamin D in both children and adults, he said, should be between 40 to 60 ng/mL.

Source: Holick MF et al. Evaluation, Treatment, and Prevention of Vitamin D Deficiency: and Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2011; 96: 0000-0000. doi:10.1210/jc.2011-0385

What African Americans should know about vitamin D and heart health

A while back, I was talking with a friend of mine. He was a giant of a black man and we spoke about his  blood pressure woes and his weight issues. So I asked him about his diet, his habits, and all that. He told me all about it: How he ate all the right foods, how he was trying to avoid the wrong ones, and how he recently started walking on his treadmill.

I said to him, "What do you do all day?"

He said, "I'm in the office all day."

"What do you do at lunchtime?"

"I usually have a protein shake or eat a salad with some chicken."

That's good, I tell him. But I want you to do one more thing. It's easy. While or after you eat, take a walk. Outside. In the parking lot. Once or twice a week.

OK, he says. "But why outside?"

I said, "Sunlight and vitamin D." Then, I told him a story we should all be familiar with by now, which went something like this:

Darker skin is a result of greater production of a pigment called melanin that rewards skin with a natural protection against ultraviolet light. Ultraviolet light would otherwise burn skin, destroy the body's stores of nutrients like folic acid that are needed for refurbishing DNA, increase risk of neural tube defects among other reproductive problems, and also raise risk of skin cancer.

So, in short, melanin is a good thing. Near the equator, with strong UVB rays aplenty to compensate slower vitamin D production, darker skin offers an evolutionary advantage that would only serve to sustain naked humans. But, as often is the case, reward comes with recompense. The downside of higher amounts of melanin is that the pigment interferes with the skin's ability to absorb enough UVB rays to activate Vitamin D's pre-cursor into a full-fledged hormone.
As is well-documented, humans at higher latitudes with dark skin would never have survived over the generations without shedding the extra melanin and opting for a lighter color. Lighter color would afford more UVB absorbed, more D created, stronger bones and, as evidence emerges to show, better cardiovascular health. During summer months, lighter-skinned humans who had migrated to higher latitudes collected vitamin D in fat as they gained weight, then released it into the bloodstream when they shed weight during sunlight-lacking winter months.


On the other hand, when darker-skinned humans live in a Northern latitudes of the United States -- as African Americans do -- you can bet that problems will arise.

Then, I gave him some details about asking his doctor for a 25-hydroxyvitamin D test.

A couple of weeks later, I spotted him outside walking around a parking lot. He tells me, "Thanks so much, David. I had no idea about vitamin D. Plus, my doctor says the walking and the vitamin D are helping my heart."

While attending Experimental Biology (#eb2011) over the weekend, one of the presentations had me thinking about my friend. And that was Richard Harris, Ph.D., of Georgia Health Sciences University in Augusta, presenting a study on vitamin D supplementation in African Americans.


What Dr. Harris and his fellow Georgia researchers found was that vitamin D supplementation in overweight African American adults in a single dose of 60,000 IU every for four weeks every 16 weeks improved blood vessel endothelial function – the equivalent of 2,000 IU since vitamin D has a half life of about three weeks.

It was notable that they used overweight adults, since extra weight can increase blood volume, raise blood pressure, resulting in rigid, inflamed vessels. Details are that the researchers used an inflatable cuff to increase blood flow in the brachial arteries of each of the participants, then an ultrasound to measure flow-mediated dilation.

What exactly vitamin D was able to do is what Dr. Harris calls the "million-dollar question," according to this press release. But it's likely that the hormone acted directly on endothelial cells, on a receptor perhaps, that helps dilate blood vessels when needed. The more dilation, the easier it is for blood to flow through vessels.

This study is great news, especially for this population at higher risk for cardiovascular disease factors like higher blood pressure. However, there is still too little vitamin D deficiency awareness.

Here's what I say, Why not teach African Americans why they have a greater need for vitamin D from an evolutionary perspective?

In the case of my friend, it really helped put things in perspective. There's an easy solution for this mess, which is to take a walk around the block for a few minutes when UVB rays are out (mostly just in summer months) or, simply, by just taking a vitamin D supplement as they did in the summer. Lots of benefits to come from such an easy habit of getting D daily like better blood pressure along with better bone health.

Another thing is that the Institute of Medicine's recommended daily intakes of vitamin D (although they are based as if there were no sun-produced D at all) just make little sense when they don't treat all adults the same, not bringing high-risk groups into consideration. Until more research is available and the IOM can build on current guidelines by raising them for high-risk groups, African Americans should take health into their own hands by getting tested to make sure they keep 25-hydroxyvitamin D in healthy ranges continually.   

Vitamin D production from UV radiation: The effects of total cholesterol and skin pigmentation

Our body naturally produces as much as 10,000 IU of vitamin D based on a few minutes of sun exposure when the sun is high. Getting that much vitamin D from dietary sources is very difficult, even after “fortification”.

The above refers to pre-sunburn exposure. Sunburn is not associated with increased vitamin D production; it is associated with skin damage and cancer.

Solar ultraviolet (UV) radiation is generally divided into two main types: UVB (wavelength: 280–320 nm) and UVA (320–400 nm). Vitamin D is produced primarily based on UVB radiation. Nevertheless, UVA is much more abundant, amounting to about 90 percent of the sun’s UV radiation.

UVA seems to cause the most skin damage, although there is some debate on this. If this is correct, one would expect skin pigmentation to be our body’s defense primarily against UVA radiation, not UVB radiation. If so, one’s ability to produce vitamin D based on UVB should not go down significantly as one’s skin becomes darker.

Also, vitamin D and cholesterol seem to be closely linked. Some argue that one is produced based on the other; others that they have the same precursor substance(s). Whatever the case may be, if vitamin D and cholesterol are indeed closely linked, one would expect low cholesterol levels to be associated with low vitamin D production based on sunlight.

Bogh et al. (2010) recently published a very interesting study. The link to the study was provided by Ted Hutchinson in the comments sections of a previous post on vitamin D. (Thanks Ted!) The study was published in a refereed journal with a solid reputation, the Journal of Investigative Dermatology.

The study by Bogh et al. (2010) is particularly interesting because it investigates a few issues on which there is a lot of speculation. Among the issues investigated are the effects of total cholesterol and skin pigmentation on the production of vitamin D from UVB radiation.

The figure below depicts the relationship between total cholesterol and vitamin D production based on UVB radiation. Vitamin D production is referred to as “delta 25(OH)D”. The univariate correlation is a fairly high and significant 0.51.

25(OH)D is the abbreviation for calcidiol, a prehormone that is produced in the liver based on vitamin D3 (cholecalciferol), and then converted in the kidneys into calcitriol, which is usually abbreviated as 1,25-(OH)2D3. The latter is the active form of vitamin D.

The table below shows 9 columns; the most relevant ones are the last pair at the right. They are the delta 25(OH)D levels for individuals with dark and fair skin after exposure to the same amount of UVB radiation. The difference in vitamin D production between the two groups is statistically indistinguishable from zero.

So there you have it. According to this study, low total cholesterol seems to be associated with impaired ability to produce vitamin D from UVB radiation. And skin pigmentation appears to have little  effect on the amount of vitamin D produced.

I hope that there will be more research in the future investigating this study’s claims, as the study has a few weaknesses. For example, if you take a look at the second pair of columns from the right on the table above, you’ll notice that the baseline 25(OH)D is lower for individuals with dark skin. The difference was just short of being significant at the 0.05 level.

What is the problem with that? Well, one of the findings of the study was that lower baseline 25(OH)D levels were significantly associated with higher delta 25(OH)D levels. Still, the baseline difference does not seem to be large enough to fully explain the lack of difference in delta 25(OH)D levels for individuals with dark and fair skin.

A widely cited dermatology researcher, Antony Young, published an invited commentary on this study in the same journal issue (Young, 2010). The commentary points out some weaknesses in the study, but is generally favorable. The weaknesses include the use of small sub-samples.

References

Bogh, M.K.B., Schmedes, A.V., Philipsen, P.A., Thieden, E., & Wulf, H.C. (2010). Vitamin D production after UVB exposure depends on baseline vitamin D and total cholesterol but not on skin pigmentation. Journal of Investigative Dermatology, 130(2), 546–553.

Young, A.R. (2010). Some light on the photobiology of vitamin D. Journal of Investigative Dermatology, 130(2), 346–348.

Vitamin D status affected by obesity

People who are overweight or obese are more likely to have lower circulating levels of vitamin D and may have trouble with conversion to its hormonally active form, a Norwegian study suggests.

These findings, published in the Journal of Nutrition, may partially explain why carrying extra pounds raises risk of several poor health outcomes linked to low vitamin D. The hormonally active form is critical for maintaining cell health, strong bones, a strong immune system, and a healthy heart and brain.

University of Oslo researchers observed almost 1,800 people for six years—about 62 percent obese and 11 percent morbidly obese as indicated by Body Mass Index (BMI)—and found an inverse relationship between higher BMI and serum concentrations of circulating 25(OH)2D and the hormonally active 1,25(OH)2D.

A seasonal variation of both vitamin D metabolites in the obese subjects provided clues that excess weight disturbed the complicated conversion (hydroxylation) of the circulating 25(OH)2D to hormonaly active 1,25(OH)2D in the kidneys.

The authors suggest that measurement of both serum concentrations, 25(OH)2D to 1,25(OH)2D, in overweight and obese persons may be valuable because of “the reduced bioavailability” of the fat-soluble vitamin that “accumulates in excess body fat and muscular tissue.”

The research confirms prior studies’ findings that people who are overweight or obese may need to obtain higher amounts of vitamin D from sun exposure, diet or supplementation. In addition, achieving a healthier BMI is predicted as a way to improve vitamin D status.

Several other factors affect vitamin D status, and include lack of sunlight exposure, skin with higher melanin content (darker skin), older age, low dietary intake, and impaired ability to absorb vitamin D from the diet.

Source: Lagunova Z, Porojnicu AC, Vieth R, Lindberg FA, Hexeberg S and Moan J. Serum 25-Hydroxyvitamin D is a Predictor of Serum 1,25-Dihydroxyvitamin D in Overweight and Obese Patients. J Nutr 2011; 141: 112-117. doi: 10.3945/​jn.109.119495.

My thoughts:

I found this to be an interesting paper. The point is that one of the big reasons for why obesity leads to poor health is because it wrecks your ability to use a powerful hormone, vitamin D. People overweight need more vitamin D to cope, plus will improve vitamin D status when they lose weight. A big deal.

What is a reasonable vitamin D level?

The figure and table below are from Vieth (1999); one of the most widely cited articles on vitamin D. The figure shows the gradual increase in blood concentrations of 25-Hydroxyvitamin, or 25(OH)D, following the start of daily vitamin D3 supplementation of 10,000 IU/day. The table shows the average levels for people living and/or working in sun-rich environments; vitamin D3 is produced by the skin based on sun exposure.

25(OH)D is also referred to as calcidiol. It is a pre-hormone that is produced by the liver based on vitamin D3. To convert from nmol/L to ng/mL, divide by 2.496. The figure suggests that levels start to plateau at around 1 month after the beginning of supplementation, reaching a point of saturation after 2-3 months. Without supplementation or sunlight exposure, levels should go down at a comparable rate. The maximum average level shown on the table is 163 nmol/L (65 ng/mL), and refers to a sample of lifeguards.

From the figure we can infer that people on average will plateau at approximately 130 nmol/L, after months of 10,000 IU/d supplementation. That is 52 ng/mL. Assuming a normal distribution with a standard deviation of about 20 percent of the range of average levels, we can expect about 68 percent of the population to be in the 42 to 63 ng/mL range.

This might be the range most of us should expect to be in at an intake of 10,000 IU/d. This is the equivalent to the body’s own natural production through sun exposure.

Approximately 32 percent of the population can be expected to be outside this range. A person who is two standard deviations (SDs) above the mean (i.e., average) would be at around 73 ng/mL. Three SDs above the mean would be 83 ng/mL. Two SDs below the mean would be 31 ng/mL.

There are other factors that may affect levels. For example, being overweight tends to reduce them. Excess cortisol production, from stress, may also reduce them.

Supplementing beyond 10,000 IU/d to reach levels much higher than those in the range of 42 to 63 ng/mL may not be optimal. Interestingly, one cannot overdose through sun exposure, and the idea that people do not produce vitamin D3 after 40 years of age is a myth.

One would be taking in about 14,000 IU/d of vitamin D3 by combining sun exposure with a supplemental dose of 4,000 IU/d. Clear signs of toxicity may not occur until one reaches 50,000 IU/d. Still, one may develop other complications, such as kidney stones, at levels significantly above 10,000 IU/d.

See this post by Chris Masterjohn, which makes a different argument, but with somewhat similar conclusions. Chris points out that there is a point of saturation above which the liver is unable to properly hydroxylate vitamin D3 to produce 25(OH)D.

How likely it is that a person will develop complications like kidney stones at levels above 10,000 IU/d, and what the danger threshold level could be, are hard to guess. Kidney stone incidence is a sensitive measure of possible problems; but it is, by itself, an unreliable measure. The reason is that it is caused by factors that are correlated with high levels of vitamin D, where those levels may not be the problem.

There is some evidence that kidney stones are associated with living in sunny regions. This is not, in my view, due to high levels of vitamin D3 production from sunlight. Kidney stones are also associated with chronic dehydration, and populations living in sunny regions may be at a higher than average risk of chronic dehydration. This is particularly true for sunny regions that are also very hot and/or dry.

Reference

Vieth, R. (1999). Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. American Journal of Clinical Nutrition, 69(5), 842-856.

New vitamin D guidelines, a disappointment

Over the past decade, there has been tremendous excitement in the world of nutrition centered around the "sunshine vitamin" for its association with reducing risk of influenza, osteoporosis, autoimmune diseases, heart disease, and even some cancers such as prostate and breast cancer. 

However, this morning, the Institute of Medicine, of the National Academy of Sciences released new guidelines for vitamin D (and calcium) that will come as a disappointment to several researchers who consider the report too conservative to deal with a widespread epidemic.

"Vitamin D is the most common medical condition in the world, believe it or not" said Michael Holick, of Boston University Medical Center, to me in a recent interview. Holick, who routinely prescribes 2000-3000 IU per day to his patients, has studied Vitamin D for more than 40 years. In the 1970s he was the first to isolate the major circulating form of Vitamin D in plasma, 25-hydroxyvitamin D, as well as the active form produced in the kidneys. 

In his recently published book, The Vitamin D Solution, Holick cites evidence that: 

• Half of all children in the US and Europe are Vitamin D deficient at some time, but almost every single one has vitamin D insufficiency.
• Over the last 10 years there's been 22 percent reduced levels of vitamin D in the US
• Last year, a study published in Archives of Internal Medicine, showed 70 percent of whites, 90 percent of Hispanics and 97 percent of blacks in the US have insufficient levels.
• Even near the equator (where you'd think people were getting plenty of sun –think Saudi Arabia, India, Australia, Brazil, Mexico – between 30 to 80 percent of children and adults are deficient or insufficient.
• Three out of four people in the US are deficient, most are insufficient. Twenty years ago it was only 1 out of 2.
• New research has linked several common problems of poor health and accelerated aging to one single thing – vitamin D deficiency or insufficiency

Despite these data, the IOM reported that most people in the U.S. and Canada should be able to obtain sufficient amounts from their diet to meet Dietary Recommended Intakes (DRIs), assuming no other vitamin D was synthesized from the sun in the skin.

The IOM raised the DRIs of vitamin D to 600 International Units (IU) for ages 1-70 and to 800 IU for ages 70 and older. Previously the DRIs were 200 IU for ages 1-50, 400 IU for ages 51-70, and 600 IU for ages 70 and older.

The Tolerable Upper Limit was also raised from 2,000 IU to 4,000 IU for adults, which will allow major manufacturers such as the dairy industry and Coca Cola who make Minute Maid orange juice to consider doubling vitamin D in their products.

The IOM committee chair Catharine Ross, of Penn State, said that after reviewing more than 1,000 published studies and listening to testimonies of scientists there still wasn't enough solid evidence for raising vitamin D DRIs or ULs any higher.

In a press conference this morning, she said, "What we were not able to do is take the currently available clinical data including randomized clinical trials and use that information for Dietary Recommended Intakes. The data are not sufficient at present to conclude that intakes should be higher."

When asked about why the Upper Limit was not raised higher, Ross said, "We needed to take a cautious approach because we're looking to reduce risk to the public. There's evidence of harm at the level of 10,000 IU. So we used 4000 IU per day." She said that there was a gap in evidence in between the two numbers.

Other scientists on the committee chimed in:

"There's considerably more evidence, a tremendous amount for vitamin D," said Patsy Brannon, of Cornell, yet not enough to guide decision making on greater intake. She added, "There is research that points to risk. There's also research that shows no risk. We also lack RCTs. We're still needing more research."

Oncologist Steven Clinton, of Ohio State University, said, "As you look across the literature there are inconsistencies." For example, regarding calcium, it's associated with less colon polyps, but increased risk in prostate cancer. He says that in the future as more data become available, there will be more individualized approaches.

"We are still interested in this molecule that affects thousands of genes in the body. But we cannot make this leap at this point," added biochemist Glenville Jones, of Queens University.

The committee had been asked to set new guidelines for DRIs of calcium and vitamin D as well as Upper Limit intakes.

What about supplements?

Despite headlines from the New York Times and several other news outlets, the IOM committee voiced that they did not intend for this kind of position and clarified that they did not specify where the vitamin D amounts should come from--whether it be from the sun, supplements or diet.

Clinton added that, "especially in Canada, we don't want to close the door on those supplements. There's possibility of using supplements." Although, he said he wondered about whether or not the Canadian Cancer Society would change its recommendation from 1,000 IU to 600-800 IU in light of the IOM's new recommendations.

When asked what to make of the new recommendations when it's clear that skin synthesis upon sun exposure yielded amounts of 20000 IU or higher, Brannon responded: "We set our recommendations based on data for total consumption of vitamin D."

She added that the difference between dietary intakes and the skin synthesis is that the body has a natural ability to rid itself of excess made by the sun, "The sun giveth, the sun taketh away."

Apart from Holick, other scientists have voiced their opinions like those representing the Vitamin D Council: Bruce Hollis of Medical University of South Carolina and Robert Heaney of Creighton University.

They have long recommended taking a supplement by as much as 5,000 IU per day to maintain blood levels between 50-80ng/mL year-round.

As Science News reports, Hollis called the IOM report "a big waste of money," although agreed with the panel's decision to double recommendations for children. In addition, Heaney said, “I don’t think this does anything to create confidence in IOM recommendations."

The entire IOM report is summed up by registered dietitian Debra Riedesel, who posted on Twitter, as @NutritionistaRD, in response to the debate, "Do you trust the scientists who've researched Vit D for years or 14 IOM scientists who only read the research?"

The baffling rise in seasonal allergies: Global warming or obesity?

The July 26, 2010 issue of Fortune has an interesting set of graphs on page 14. It shows the rise of allergies in the USA, together with figures on lost productivity, doctor visits, and medical expenditures. (What would you expect? This is Fortune, and money matters.) It also shows some cool maps with allergen concentrations, and how they are likely to increase with global warming. (See below; click on it to enlarge; use the "CRTL" and "+" keys to zoom in, and CRTL" and "-" to zoom out.)

The implication: A rise in global temperatures is causing an increase in allergy cases. Supposedly the spring season starts earlier, with more pollen being produced overall, and thus more allergy cases.

Really!?

I checked their numbers against population growth, because as the population of a country increases, so will the absolute number of allergy cases (as well as cancer cases, and cases of almost any disease). What is important is whether there has been an increase in allergy rates, or the percentage of the population suffering from allergies. Well, indeed, allergy rates have been increasing.

Now, I don’t know about your neck of the woods, but temperatures have been unusually low this year in South Texas. Global warming may be happening, but given recent fluctuations in temperature, I am not sure global warming explains the increases in allergy rates. Particularly the spike in allergy rates in 2010; this seems to be very unlikely to be caused by global warming.

And I have my own experience of going from looking like a seal to looking more like a human being. When I was a seal (i.e., looked like one), I used to have horrible seasonal pollen allergies. Then I lost 60 lbs, and my allergies diminished dramatically. Why? Body fat secretes a number of pro-inflammatory hormones (see, e.g., this post, and also this one), and allergies are essentially exaggerated inflammatory responses.

So I added obesity rates to the mix, and came up with the table and graph below (click on it to enlarge).

Obesity rates and allergies do seem to go hand in hand, don’t you think? The correlation between obesity and allergy rates is a high 0.87!

Assuming that this correlation reflects reasonably well the relationship between obesity and allergy rates (something that is not entirely clear given the small sample), obesity would still explain only 75.7 percent of the variance in allergy rates (this number is the correlation squared). That is, about 24.3 percent of the variance in allergy rates would be due to other missing factors.

A strong candidate for missing factor is something that makes people obese in the first place, namely consumption of foods rich in refined grains, seeds, and sugars. Again, in my experience, removing these foods from my diet reduced the intensity of allergic reactions, but not as much as losing a significant amount of body fat. We are talking about things like cereals, white bread, doughnuts, pasta, pancakes covered with syrup, regular sodas, and fruit juices. Why? These foods also seem to increase serum concentrations of pro-inflammatory hormones within hours of their consumption.

Other candidates are vitamin D levels, and lack of exposure to natural environments during childhood, just to name a few. People seem to avoid the sun like the plague these days, which can lower their vitamin D levels. This is a problem because vitamin D modulates immune responses; so it is important in the spring, as well as in the winter. The lack of exposure to natural environments during childhood may make people more sensitive to natural allergens, like pollen.

Michael Holick on Vitamin D

Michael Holick, MD, PhD, of Boston University Medical Center says he’s “just one of the many scientists” exploring vitamin D, but he easily can be considered the world’s foremost authority on the sunshine vitamin.

In the 1970s, it was Dr. Holick who first isolated the major circulating form of vitamin D in plasma, 25-hydroxyvitamin D, as well as the active form produced by the kidneys.

He was also one of the first scientists to warn the medical community about the potential implications of widespread vitamin D insufficiency. When asked about the prevalence of low vitamin D status, he answers that it’s the “most common medical condition in the world, believe it or not.”

Dr. Holick has championed the cause of bringing vitamin D into the limelight for decades, writing numerous scientific papers as well as two popular books on the subject of vitamin D and health.

Getting D Facts from Dr. Holick

While seeking the latest findings from vitamin D research, I caught up with Dr. Holick and sought out his advice on sun exposure, vitamin D supplementation and vitamin D’s potential ties to weight management, insulin resistance and heart health.*

Q: Dr. Holick, thank you for taking the time to update us on vitamin D research. Elvis Presley once said, “Truth is like the sun. You can shut it out for a time, but it ain’t going away.” Don’t you think this quote represents the vitamin D story?

A: Amen. Elvis was right on target. Our sun has been demonized for 40 years unchallenged. It’s quite remarkable that it’s part of the psyche of the world. But it’s caused a major problem, which is worldwide vitamin D deficiency [or insufficiency] and markedly increased risk of chronic disease for children and adults.

You can instantly make vitamin D, but if you’re avoiding the sun as most people do it puts you at high-risk of deficiency. Why is that? It’s been demonized for so long because the dermatologists have come out with the big “C” word [melanoma skin cancer from sun exposure]. And there’s no question that skin cancer is on the rise. The major reason is because back in the ’60s people used to put baby oil on and bake in the sun. Right? Now, all of the sudden, that’s starting to haunt them later in life. It increased their risk of non-melanoma skin cancer.

But often what people don’t realize is that melanoma, the most deadly cancer—which is also what they lump together with skin cancer from the sun—most melanomas occur on the least sun-exposed areas. Occupational sun exposure decreases your risk of developing melanoma. There was a study done in a group in Texas that if you had the most sun exposure as a child and young adult and you did get melanoma, then you were more likely to survive it.

Q: Would you comment on vitamin D being a hormone, and the oldest hormone?

A: Well, the reason why we say that [it's the oldest hormone] is because I asked the question several years ago. If you take phytoplankton—there’s a phytoplankton species called Emiliani huxleii has been identified as one of the oldest phytoplankton species that has been unchanged for 750 million years. When we looked at that organism, it made a huge amount of vitamin D when it was exposed to sunlight.

It’s a hormone you make in your skin, then it’s inactive. It has to go to your liver to get hydroxylated to 25-hydroxyvitamin D, which is the major circulating form, the form you should ask your doctor to test for vitamin D status. Then it goes to your kidneys where it’s activated to 1,25-dihydroxyvitamin D, then it goes to your bone and intestines and kidneys.

Q: As a hormone, we also know now that it has a greater role on the body besides speeding up absorption of calcium for bone health. There is a link to cardiovascular health, right? What’s the state of the science?

A: As for the heart, we know that vascular smooth muscle cells have vitamin D receptors and we know that vitamin D seems to play a role in regulating blood pressure, regulating heart muscle cells in their growing activity, regulates to some degree the strength of the heart in terms of its pumping ability. That’s why it’s not at all surprising that just two years ago out of the Framingham heart study it shows that if you are vitamin D deficient you [are not providing optimal support for cardiovascular health].

Q: How does vitamin D’s relationship to heart health affect you if you are overweight?

A: This issue for obese people is particularly important because vitamin D is fat-soluble and is incorporated in your body fat. We showed many years ago that if you take an obese person and give him an oral dose of vitamin D or put him in a [UVB] tanning bed, it only raises his blood level to less than 50 percent than what a normal-weighted individual does and we’re talking about a BMI [Body Mass Index] of greater than 30. He needs two to three times more [of vitamin D than a person of normal BMI].

We know that obese people have more aches in their muscles, which is definitely due to vitamin D deficiency. They have muscle weakness. They’re fatigued. They just don’t want to go. It’s in part due to the deficiency. We also know that fat cells have a vitamin D receptor. There’s some evidence—we’re doing some research right now—that suggests that maybe vitamin D helps keep fat cells in check.

Q: Really? By what mechanism is it that you think vitamin D could help keep fat cells in check?

A: It may regulate fat cell maturation. It may regulate fat cell fat accumulation. That’s brand new stuff that we’re taking a look at that we’ve not yet published on. We’re just beginning to look at it.

Q: Is there any relationship established between low vitamin D status and insulin sensitivity?

A: We think so. We know that from NHANES (National Health and Nutritional Examination Survey) that [there may be a relationship associated with insulin sensitivity].

Q: We’ve heard a lot about a new established relationship between vitamin D and the immune system. Would you comment on the mechanism by which vitamin D is involved?

A: Well we know is that your immune system is regulated by vitamin D. We know that the cell macrophages definitely gobble up infectious agents because of vitamin D, macrophages activate vitamin D locally, and it stimulates production of a defensive protein that kills infectious agents. A study was done to show that if you raise your blood level, that you have more activity of your macrophages in killing infective agents. If there’s anything out there that helps to support the immune system, it’s probably vitamin D.

Q: Do you agree that everyone should be checked for vitamin D status?

A: Well, that’s the problem. It’s not an unreasonable thing to do, but I can already tell you they’re deficient. We know almost everyone’s deficient. If a normal adult isn’t taking at least 1,500 to 2,000 IU from supplement and diet—and you can’t really get it from your diet—then we know you’re vitamin D deficient. And so, to try to screen everybody, all the obese people in the United States is such a huge cost burden.

In fact, Medicare is looking at this right now and wanting to control the doctors’ use of that assay. They do not want to use it as a screening tool. I don’t disagree with that. Because we know that you can very effectively correct vitamin D deficiency, treat it, and prevent it from occurring again, if you give the person enough vitamin D. So only if they have fat malabsorption syndrome, or has had gastric bypass surgery, or cystic fibrosis, IBD, or celiac sprue—all of those individuals should be tested because you can’t predict whether or not they’re going to be able to absorb the vitamin D that you give them as a supplement.

Q: What about older people? Does the requirement for vitamin D supplementation increase with older age because of declined absorption?

A: No it does not. That’s what everybody says. [Note: Elderly can absorb vitamin D as easily as younger people.] What does change with age is the ability to make it in your skin. We showed many years ago that if you compare a 70-year-old to a 20-year-old, the 70-year-old will have about a 70 percent reduced ability to produce vitamin D. But we also went on to show that you can take an older person and still have them exposed to sunlight or simulated sunlight and they make a lot of vitamin D. Your body has a huge capacity to make vitamin D. We showed that healthy adults in bathing suits getting a minimal erythermal dose get an equivalent to ingesting 20,000 IU of vitamin D.

Now you begin to understand why the 100 IU in a glass of milk or orange juice or the 400 IU in a multivitamin is probably one tenth of what we really need to satisfy our body’s requirements for heart health or for reducing risk diseases.

Q: Do you agree as other scientists have suggested that the average person should be getting at least 20 minutes of sunshine per day for adequate vitamin D intake along with supplementation?

Dr. Holick has been researching vitamin D since the 1970s.
A: I don’t know about 20 minutes a day because it depends upon time of day, season of the year, latitude, and your degree of skin pigmentation. What I tell people is, if you know that you’re going to be out in June at noon-time for 30 minutes, in Arizona, and you’re going to get a light sunburn to your skin, to go out 50 percent of that time.

Always protect your face, it’s the most sun exposed, the most sun damaged. But you can certainly expose your arms and legs and not worry about it, in my opinion. Abdomen, back, not a problem. The more skin you expose, the more [vitamin D] that you make.

Q: Do you expect the Institute of Medicine’s recommendations for Adequate Intake of vitamin D to change in the United States anytime soon to reflect findings of new research?

A: Yes, there will definitely be new Adequate Intakes. What you really care about though is not the AI recommendation, what you care about is the Upper Limit—that’s what prevents manufacturers from putting vitamin D into foods. The amounts that you can put in and the amounts that supplements can contain.

The safe upper limit right now is considered to be 2,000 IU for adults. The major manufacturers like Coca Cola or who make Minute Maid orange juice for example put only 100 IU in a glass, because if they put in any more then they start adding that up, drinking milk and taking a multivitamin, you’re over the 2,000 IU limit.

Then if you get some toxicity like a kidney stone, it doesn’t matter that it’s not due to the vitamin D, the lawyers will say that it is if you put more than you should’ve put in. So they need to increase it like to 10,000 IU in which case, then we can really have an impact on the entire U.S. population and the world’s population because they could now put more vitamin D in the food.

Q: Dr. Holick, this has been very interesting and I’m sure it will be interesting to our readers. Thank you for your time. Also, congrats on the new book. We’ll be ordering a couple of copies for our library.

A: Wonderful. Feel free to stay in touch

Low muscle mass linked to diabetes

Being overweight is a risk factor for type 2 diabetes; however, a new study shows losing weight alone may not be enough to reduce risk of type 2 diabetes in people with low muscle mass and strength, particularly if they are over the age of 60.

These are the findings of new research from Dr. Preethi Srikanthan of University of California, Los Angeles, and colleagues who performed a cross-sectional analysis of 14,528 people from National Health and Nutrition Examination Survey III.

Dr. Srikanthan and colleagues concluded that age-related muscle loss, or sarcopenia, was associated with greater insulin resistance; and, sarcopenia, independent of obesity, may be an early predictor of diabetes. This association of sarcopenia and insulin resistance was strongest in those who were 60 years and older, the researchers warn.

Apart from these poor health outcomes, sarcopenia in older adults is also clearly associated with other health outcomes such as increased risk of falls, hip fractures, bone loss (osteopenia) and physical disability.
Several earlier studies suggest similarly that a direct correlation exists between sarcopenia in people ages 60 and older and greater risk of insulin resistance, metabolic syndrome, type 2 diabetes and cardiovascular disease, regardless of body weight.

Study Reference: Srikanthan P, Hevener AL, Karlamangla AS, 2010 Sarcopenia Exacerbates Obesity-Associated Insulin Resistance and Dysglycemia: Findings from the National Health and Nutrition Examination Survey III. PLoS ONE 5(5): e10805. doi:10.1371/journal.pone.0010805

Vitamin D levels: Sunlight, age, and toxicity

Calcidiol is a pre-hormone that is produced based on vitamin D3 in the liver. Blood concentration of calcidiol is considered to be a reliable indicator of vitamin D status. In the research literature, calcidiol is usually referred to as 25-Hydroxyvitamin or 25(OH)D. Calcidiol is converted in the kidneys into calcitriol, which is the active form of vitamin D.

The table below (from: Vieth, 1999; full reference at the end of this post; click on it to enlarge), shows the average blood vitamin D levels of people living or working in sun-rich environments. To convert from nmol/L to ng/mL, divide by 2.496. For example, 100 nmol/L = 100 / 2.496 ng/mL = 40.1 ng/mL. At the time of this writing, Vieth (1999) had 692 citations on Google Scholar, and probably more than that on Web of Science. This article has had, and continues having, a high impact among researchers.

The maximum average level of blood (or serum) vitamin D shown in the table is 163 nmol/L (65 ng/mL). Given that the human body produces vitamin D naturally from sunlight, it is reasonable to assume that those blood vitamin D levels are not yet at the toxic range. In fact, one of the individuals, a farmer in Puerto Rico, had a level of 225 nmol/L (90 ng/mL). That individual had no signs of toxicity.

Several studies show that pre-sunburn full-body exposure to sunlight is equivalent to an oral vitamin D intake of approximately 250 µg (10,000 IU).

In spite of claims to the contrary, vitamin D production based on sunlight does not cease after 40 years of age or so. Studies reviewed by Vieth suggest that among the elderly (i.e., those aged 65 or above) pre-sunburn full-body exposure to sunlight is equivalent to an oral vitamin D intake of 218 µg (8,700 IU).

Sunlight-induced vitamin D production does seem to decrease with age, but not dramatically.

Post-sunburn sunlight exposure does not increase vitamin D production. Since each person is different, a good rule of thumb to estimate the number of minutes of sunlight exposure needed to maximize vitamin D production is the number of minutes preceding sunburn. For a light-skinned person, this can be as little as 7 minutes.

Vitamin D accumulation in the body follows a battery-like pattern, increasing and decreasing gradually. The figure below, from Vieth’s article, shows the gradual increase in blood vitamin D concentrations following the start of daily supplementation. This suggests that levels start to plateau at around 1 month, with higher levels reaching a plateau after 2 months.

While sunlight exposure does not lead to toxic levels of vitamin D, oral intake may. Below is a figure, also from Vieth’s article, that plots blood levels of vitamin D against oral intake amounts. The X’s indicate points at which intoxication symptoms were observed. While typically intoxication starts at the 50,000 IU intake level, one individual displayed signs of intoxication at 10,000 IU. That individual received a megadose that was supposed to provide vitamin D for an extended period of time.

Non-toxic levels of 10,000 IU are achieved naturally through sunlight exposure. This applies to modern humans and probably our Paleolithic ancestors. Yet, modern humans normally limit their sun exposure and intake of vitamin D to levels (400 IU) that are only effective to avoid osteomalacia, the softening of the bones due to poor mineralization.

Very likely the natural production of 10,000 IU based on sunlight was adaptive in our evolutionary past, and also necessary for good health today. This is consistent with the many reports of diseases associated with chronic vitamin D deficiency, even at levels that avoid osteomalacia. Among those diseases are: hypertension, tuberculosis, various types of cancer, gingivitis, multiple sclerosis, chronic inflammation, seasonal affective disorder, and premature senescence.

Reference:

Reinhold Vieth (May 1999). Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. American Journal of Clinical Nutrition, Vol. 69, No. 5, 842-856.

How much vitamin D? Vitamin D Council's recommendations

Since my recent post on problems related to vitamin D deficiency and excess I received several questions. I have also participated in several discussions in other blogs related to vitamin D in the past few days.

There is a lot of consensus about vitamin D deficiency being a problem, but not much about vitamin D in excess being a problem as well.

Some bloggers recommend a lot of supplementation, which may be dangerous because: (a) our body evolved to obtain most of its vitamin D from a combination of sunlight exposure and cholesterol, and thus body accumulation regulation mechanisms are not designed to deal with excessive oral supplementation; and (b) vitamin D, like many fat-soluble vitamins, accumulates in fat tissue over time, and is not easily eliminated by the body when in excess.

The Vitamin D Council has the following general recommendation regarding supplementation:

Take an average of 5,000 IU a day, year-round, if you have some sun exposure. If you have little, or no, sun exposure you will need to take at least 5,000 IU per day. How much more depends on your latitude of residence, skin pigmentation, and body weight. Generally speaking, the further you live away from the equator, the darker your skin, and/or the more you weigh, the more you will have to take to maintain healthy blood levels.

They also provide a specific example:

For example, Dr. Cannell lives at latitude 32 degrees, weighs 220 pounds, and has fair skin. In the late fall and winter he takes 5,000 IU per day. In the early fall and spring he takes 2,000 IU per day. In the summer he regularly sunbathes for a few minutes most days and thus takes no vitamin D on those days in the summer.

For those who have problems with supplementation, here is what Dr. Cannell, President of the Vitamin D Council, has to say:

For people who have trouble with supplements, I recommend sunbathing during the warmer months and sun tanning parlors in the colder months. Yes, sun tanning parlors make vitamin D, the most is made by the older type beds. Another possibility is a Sperti vitamin D lamp.

One thing to bear in mind is that if your diet is rich in refined carbohydrates and sugars, you need to change that before you are able to properly manage your vitamin D levels. You need to remove refined carbohydrates and sugars from your diet. No more white bread, bagels, doughnuts, table sugar, sodas sweetened with high-fructose corn syrup; just to name a few of the main culprits.

In fact, a diet rich in refined carbohydrates and sugars, in and of itself, may be one of the reasons of a person''s vitamin D deficiency in the case of appropriate sunlight exposure or dietary intake, and even of excessive levels of vitamin D accumulating in the body in the case of heavy supplementation.

The hormonal responses induced by a diet  rich in  refined carbohydrates and sugars promote fat deposition and, at the same time, prevent fat degradation. That is, you tend to put on body fat easily, and you tend to have trouble burning that fat.

This causes a "hoarding" effect which leads to an increase in vitamin D stored in the body, and at the same time reduces the levels of vitamin D in circulation. This is because vitamin D is stored in body fat tissue, and has a long half-life, which means that it accumulates (as in a battery) and then slowly gets released into the bloodstream for use, as body fat is used as a source of energy.

It should not be a big surprise that vitamin D deficiency problems correlate strongly with problems associated with heavy consumption of refined carbohydrates and sugars. Both lead to symptoms that are eerily similar; several of which are the symptoms of the metabolic syndrome.

Vitamin D deficiency, seasonal depression, and diseases of civilization

George Hamilton admits that he has been addicted to sunbathing for much of his life. The photo below (from: phoenix.fanster.com), shows him at the age of about 70. In spite of possibly too much sun exposure, he looks young for his age, in remarkably good health, and free from skin cancer. How come? Maybe his secret is vitamin D.

Vitamin D is a fat-soluble pro-hormone; not actually a vitamin, technically speaking. That is, it is a substance that is a precursor to hormones, which are known as calcipherol hormones (calcidiol and calcitriols). The hormones synthesized by the human body from vitamin D have a number of functions. One of these functions is the regulation of calcium in the bloodstream via the parathyroid glands.

The biological design of humans suggests that we are meant to obtain most of our vitamin D from sunlight exposure. Vitamin D is produced from cholesterol as the skin is exposed to sunlight. This is one of the many reasons (see here for more) why cholesterol is very important for human health.

Seasonal depression is a sign of vitamin D deficiency. This often occurs during the winter, when sun exposure is significantly decreased, a phenomenon known as seasonal affective disorder (SAD). This alone is a cause of many other health problems, as depression (even if it is seasonal) may lead to obesity, injury due to accidents, and even suicide.

For most individuals, as little as 10 minutes of sunlight exposure generates many times the recommended daily value of vitamin D (400 IU), whereas a typical westernized diet yields about 100 IU. The recommended 400 IU (1 IU = 25 ng) is believed by many researchers to be too low, and levels of 1,000 IU or more to be advisable. The upper limit for optimal health seems to be around 10,000 IU. It is unlikely that this upper limit can be exceeded due to sunlight exposure, as noted below.

Cod liver oil is a good source of vitamin D, with one tablespoon providing approximately 1,360 IU. Certain oily fish species are also good sources; examples are herring, salmon and sardines. For optimal vitamin and mineral intake and absorption, it is a good idea to eat these fish whole. (See here for a post on eating sardines whole.)

Periodic sun exposure (e.g., every few days) has a similar effect to daily exposure, because vitamin D has a half-life of about 25 days. That is, without any use by the body, it would take approximately 25 days for vitamin D levels to fall to half of their maximum levels.

The body responds to vitamin D intake in a "battery-like" manner, fully replenishing the battery over a certain amount of time. This could be achieved by moderate (pre-sunburn) and regular sunlight exposure over a period of 1 to 2 months for most people. Like most fat-soluble vitamins, vitamin D is stored in fat tissue, and slowly used by the body.

Whenever sun exposure is limited or sunlight scarce for long periods of time, supplementation may be needed. Excessive supplementation of vitamin D (i.e., significantly more than 10,000 IU per day) can cause serious problems, as the relationship between vitamin D levels and health complications follows a U curve pattern. These problems can be acute or chronic. In other words, too little vitamin D is bad for our health, and too much is also bad.

The figure below (click on it to enlarge), from Tuohimaa et al. (2009), shows two mice. The one on the left has a genetic mutation that leads to high levels of vitamin D-derived hormones in the blood. Both mice have about the same age, 8 months, but the mutant mouse shows marked signs of premature aging.

It is important to note that the skin wrinkles of the mice on the left have nothing to do with sun exposure; they are associated with excessive vitamin D-derived hormone levels in the body (hypervitaminosis D) and related effects. They are a sign of accelerated aging.

Production of vitamin D and related hormones based on sunlight exposure is tightly regulated by various physiological and biochemical mechanisms. Because of that, it seems to be impossible for someone to develop hypervitaminosis D due to sunlight exposure. This does NOT seem to be the case with vitamin D supplementation, which can cause hypervitaminosis D.

In addition to winter depression, chronic vitamin D deficiency is associated with an increased risk of the following chronic diseases: osteoporosis, cancer, diabetes, autoimmune disorders, hypertension, and atherosclerosis.

The fact that these diseases are also known as the diseases of civilization should not be surprising to anyone. Industrialization has led to a significant decrease in sunlight exposure. In cold weather, our Paleolithic ancestors would probably seek sunlight. That would be one of their main sources of warmth. In fact, one does not have to go back that far in time (100 years should be enough) to find much higher average levels of sunlight exposure than today.

Modern humans, particularly in urban environments, have artificial heating, artificial lighting, and warm clothes. There is little or no incentive for them to try to increase their skin's sunlight exposure in cold weather.

References:

W. Hoogendijk, A. Beekman, D. Deeg, P. Lips, B. Penninx. Depression is associated with decreased 25-hydroxyvitamin-D and increased parathyroid hormone levels in old age. European Psychiatry, Volume 24, Supplement 1, 2009, Page S317.

P. Tuohimaa, T. Keisala, A. Minasyan, J. Cachat, A. Kalueff. Vitamin D, nervous system and aging. Psychoneuroendocrinology, Volume 34, Supplement 1, December 2009, Pages S278-S286.