Kurt Harris MD

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Sunday
Aug092009

Vitamin D


First let me thank you all for your patience in waiting for this post and for your interest in the blog. I’ve lately been  a bit busy with my day job. I also have duties managing various investments and being the building maintenance and IT guy for my wife’s dental practice, so there may be slow periods from time to time as a result.

You have no doubt also noticed that this is, so far, not one of those “here is what I ate today” blogs. Nothing wrong with that - I have a good camera - it’s just not my focus. The ratio of background reading and research per post is usually high and likely to stay that way.

I am very gratified by the positive response to the site. I first began this as a resource for patients and friends only 2 months ago. I don’t have one of those page-counter-gadgets displayed but the site has had over 7,000 unique visitors and about 35,000 page hits in that time. Your interest and intelligent questions help motivate me to learn more and keep blogging, so thank you all for that.

On to the topic.

Vitamin D is a prohormone or hormone precursor and not really a vitamin. Like cortisol and the sex hormones estrogen and testosterone, it is derived from cholesterol molecules. It is technically a secosteroid, as it is derived from cholesterol with the “3’ ring broken open.

Vitamin D is phylogenetically old, being found in simple organisms that have been around for as long as 700 million years. A molecule being preserved through that much evolutionary time is usually a clue that it could be important. Ultraviolet light (UV) is part of the spectrum of solar irradiation that has bathed the earth since before life began. (Before the air was poisoned by oxygen and the ozone layer formed, there was much more incident UV than now.) Vitamin D2 (ergocalciferol) is the more ancient plant and fungal version of D and is formed from cholesterol with UV light. D2 may have originally evolved as a kind of sunscreen in these simpler organisms. Animals evolved a chemically different form of D, called D3, which is formed via UV light and 7-dehydrocholesterol. Animals with feathers or fur create D3 photochemically within the oils on their feathers or fur, and then lick themselves to get their dose of D. Humans make D3 in the bottom two layers of their epidermis in a photochemical reaction driven by UV in a narrow band centered on about 297 nanometers wavelength – known as UVB. This opens the 3 ring in 7-dehydocholesterol and there follows a quick thermally driven isomerization:

This results in vitamin D3 or cholecalciferol, which goes to the liver and is converted to 25-hydroxycholeclaciferol or 25 (OH) D. 25 (OH)D is what we are most interested in clinically and nutritionally. It is the blood and tissue levels of 25 (OH) D that determine your Vit D status. 25 (OH) D is fat soluble and stored in adipose tissue and clinically these fat stores of D have a half life of about 2 months so it takes a few months of darkness to get deficient if you start out healthy, but it would be hard to still be stoked up after 6 months of a Wisconsin winter. When you replace D orally, you are usually taking D3 as Cholecalciferol – it is absorbed in the gut and carried into the blood in chylomicrons, makes its way to the liver and is then converted to 25 (OH)D. 

The much more high-potency active form of Vit D has an extra hydroxyl group and is 1,25 (OH)D or calcitriol. Calcitriol is found in concentrations about 1000 times lower than 25 (OH) D in the serum. This is important as although 25 (OH)D has some end-organ effects, including on its own synthesis, the major hormonally active D is calcitriol. The kidney is one primary end organ mediating the classical effects of Vit D and it is here that 25 (OH)D is converted to calcitriol like this:


This calcitriol made in the kidney then circulates and acts on the classical target organs of the gut, the bones and the kidney itself. The effects on these organs center around calcium ion homeostasis. Calcium levels must be tightly controlled for proper cell functioning, so it is no surprise that calcitriol levels are tightly controlled regardless of 25 (OH)D levels. One can therefore be 25 (OH)D deficient and have normal serum calcitriol levels. That is why you must measure 25 (OH)D to assess Vitamin D status and not calcitriol. 25(OH)D in the serum is in equilibrium with tissue stores of 25 (OH)D and these levels are the ones that determine health or deficiency.

Classical effects of Vitamin D

The classical effects of Vitamin D are the ones I was taught in medical school. They have been known for the longest and are well understood. The focus is on maintaining appropriate calcium levels, as multicellullar animals that have circulatory systems need a calcium ion concentration that is fairly constant, regardless of eating schedules, hydration status, etc., in order for cells to work properly. Vitamin D and parathyroid hormone (PTH, secreted by 4 or so ridiculously tiny glands behind the thyroid gland in your neck) work in concert to balance calcium absorption in the gut, filtration of calcium and phosphorus at the kidney, and turnover of hydroxyapatite in bone. Hydroxyapatite composed of calcium and phosphorus is the “concrete” of your bones, providing compressive strength. You can think of the collagen matrix in your bones as the “steel rebar”, providing tensile strength and elasticity. A tired metaphor, but it works for me.

Your body emphasizes staying alive first, so bone strength is secondary to calcium homeostasis when push comes to shove. You could say that when calcium is short in the bloodstream, PTH will view your endoskeleton as a big reservoir containing 1 kg of calcium. When you are a Paleolithic human, with minimal clothing and forced to spend time outside foraging, your D levels and calcium levels are concordant with the way the EM2 has selected us to function. When you are a Neolithic human (like, say, a radiologist working in a windowless room and living at 45 degrees north!) your 25(OH)D levels are suddenly chronically artificially low, and hey, not my design, but now you are absorbing 15% of your dietary calcium instead of 70%, and you are peeing out more in your urine. Your serum calcium levels come before your bone strength, so now PTH (in one of it’s actions) increases and acts to encourage specialized bone cells called osteoclasts to literally start dismantling the hydroxyapatite “concrete” in your bones in order to supply your blood with calcium.

Rickets and Osteomalacia

So if you are a Neolithic human that has just been weaned, and you live in the late nineteenth century in London, which is not only far north but has what little sun is there being screened by soot, your growing skeleton may be affected by Rickets – severe hypovitaminosis D in the skeletally immature- and you may end up bow-legged or knock-kneed. If you are an adult with a mature skeleton, there will not be the same deformity, but you may have osteomalacia  - collagan matrix “rebar” is laid down but there is inadequate hydroxyapatite “concrete”. This can have a painful periostitis in addition to weakening of the bone.

Osteoporosis

Osteoporosis means lower than desirable bone density with increased fracture risk and is a condition endemic in older folks on a Neolithic diet. It is different from osteomalacia in that the ratio of collagen matrix “rebar” to hyroxyapatite “concrete” is correct, but the total bone mass and density is low. Neolithic osteoporosis is probably multifactorial, in my opinion mostly caused by excess grain consumption, inadequate consumption of animal products in general and animal fats in particular, and is likely most related to low vitamin D and low Vitamin K2. When the D deficiency is severe, there is secondary hyperparathyroidism and PTH is measurably elevated in response to low calcium levels. Vitamin K2, especially Menaquinone or M4, is a cofactor for osteocalcin (which helps make bone) and Matrix Gla protein (which helps remodel or remove it). Please see Stephan’s fascinating posts on the importance of K2 for proper maxillofacial development, bone and dental health and cardiovascular health. K2 is also important to blood clotting and also seems to be part of the atherosclerosis puzzle – it helps to prevent atherosclerotic vascular calcification and some animal studies suggest it may reverse vascular calcifications. So K2 is needed both to make bone and to remove bony or bone-like calcifications.

For osteoporosis treatment, trials in Japan suggest K2 supplementation is highly efficacious, with one trial showing 80% reduction in hip fractures with K2 supplementation. This is much more impressive than the rather modest improvements in fracture risk reported so far with Vitamin D supplementation, but to be fair, the doses used with D have been very small, in the 400 -800 iu/day range. More on doses later. Calcium supplements seem to be the least helpful for osteoporosis, which makes sense when you understand that absorption from the gut can be very poor without D and very high with adequate D levels. It is not logical that we should need calcium as a supplement at all as long as D3 and K2 are at Paleolithic levels and you are not binding up dietary calcium with phytates in cereal grains. (Yeah, I know, you can soak the grains overnight, but that does nothing to the gliadin proteins and wheat germ agglutinin. Exactly how many reasons do you need to not eat grains?)

Vitamin D receptors (see below) are also found on skeletal muscle cells. Many fractures in the elderly may be related to muscle weakness contributing to more falls. It is speculated that in addition to age-related sarcopenia (loss of muscle mass with age) causing muscle weakness, there may be muscle weakness from lack of Vitamin D to properly stimulate muscle cells.

Vitamin D, grain avoidance and eating grass-fed butter and hard cheeses (for the K2) are my strong recommendations for avoiding osteoporosis. I doubt if bisphosphonate drugs work better, and there is no way they are safer than butter.

Non-classical effects of Vitamin D 

It seems that this hormone does much more that “just” regulate calcium ion homeostatis. The vitamin D receptor, or VDR, is a nuclear receptor. Nuclear receptors are found within the cell, sometimes on the nucleus itself, and are bound by the signaling hormone when it enters the cell. The hormone-receptor complex attaches to a specific site adjacent to the location of a gene on your DNA inside the nucleus, inducing the DNA to be “read” and transcribed into a protein. The gene turned on and the protein produced will be specific to the cell type and this explains how a single hormone can cause mutiple effects in the body depending on the type of cell having the receptor.

In the case of Vitamin D, there are VDRs found in many cells besides the Kidney, small intestine, bone cells and parathyroid gland we discussed above.

Immune function

VDRs are found on B and T lymphocytes and monocytes, all cells involved in immune function. D3’s effect on immune function improves resistance to infection by strengthening the innate immune system, for instance by supporting phagocytosis and destruction of invading organisms. D3 also modulates the adaptive immune response to better differentiate self from non-self. This latter effect, modulation of the adaptive immune response, appears to be involved in the ability of Vitamin D to decrease susceptibility to serious and common autoimmune disorders like Type I diabetes, rheumatoid arthritis and multiple sclerosis. Now, this does not mean these diseases are caused by hypovitaminosis D. In fact, Peter discusses how these are Neolithic diseases of molecular mimicry caused by other elements of Neolithic nutrition, namely interaction of a leaky gut from gluten grains and overgrowth of commensal organisms in our guts caused by starches and fiber in amounts that are not optimal. For now, you can search these diseases on Peter’s blog to learn more. I will post more of my thoughts on this phenomenon later.

I view Vitamin D deficiency as just one more Neolithic discordance with the EM2 that increases the likelihood of these autoimmune diseases of civilization, not as the primary cause.

Other elements of PaNu will interact synergistically with restoring Vitamin D to Paleolithic levels, including moderation of insulin levels and correction of the 6:3 ratio. All will conspire to improve immune function, both in terms of improving resistance to infection, decreasing promotion of common cancers, and reducing inappropriate immune responses directed against self-proteins (autoimmune diseases).

Cancer

In addition to immune cells that may control cancer promotion, cells of tissues susceptible to cancer also express the VDR. Vitamin D binds to the VDR and new proteins are synthesized that control cell differentiation, proliferation and recognition of adjacent cells, all functions important in the development of cancer.

The evidence that hypovitaminosis D causes cancer is mostly epidemiologic, but is powerfully suggestive, and unlike, say, the diet/heart hypothesis (cholesterol or saturated fat causing heart disease), has the virtue of biological plausibility and support by laboratory science. The evidence can be summarized thusly:

A wealth of studies show that exposure to UV light (latitude) and in some cases vitamin D intake or serum levels, are inversely related to the risk of common cancers, including colon, breast, prostate, esophagus and non-Hodgkin lymphoma. African Americans are particularly likely to be D deficient and have higher rates of many cancers, especially when they live at higher latitudes. The same latitude epidemiology supports the effect of D on risk of MS diabetes and hypertension.  One review suggested that supplementation with 1000 iu/day D3 would decrease colon cancer by as much as 50%. There is evidence both for reduced incidence (risk of getting cancer) and reduced mortality if you get it. Making sure my Vitamin D levels were high is the first thing I would do if I were diagnosed with cancer. 

A trial from Creighton University investigating calcium and Vitamin D at 1100 iu/day for fracture prevention “accidentally” showed 60% lower cancer risk in women over a 4 year period.

Other Effects

Vitamin D replacement improves insulin sensitivity, beta cell function (ability to secrete insulin) and hypertension. Interestingly, these are all effects that counter elements of metabolic syndrome. Vitamin D can be thought of as an anti-metabolic syndrome hormone. How much of Neolithic disease is due to hypovitaminosis D? It certainly seems to be an element. My suspicion is that, like fructose avoidance and maybe lack of excess linoleic acid, high D levels may be one of those things that increase our tolerance for carbohydrates – think of the Kitavans with their high carbohydrate diet but no evidence of metabolic syndrome and preserved glucose homeostasis.

Replacement, Not Supplementation

OK, so now I sound like all the other bloggers. I don’t really believe in supplementation, but......

I have talked previously about my view of the distinction between supplementation, compensatory supplementation and replacement. Supplementation is the belief that there is something magic that was not present in Paleolithic life that can give us “supranormal” health. The belief in dietary antioxidants or novel drugs or eating lots of some unusual particular food is supplementation. It is generally not biologically plausible that there is some completely novel element that can improve health. 

What are the sources of Vitamin D? Even in the deficient population, 80% or more of serum 25(OH)D is attributable to sunlight. Sunlight is effectively the only natural source of significance. You can get some D from fish, beef liver, irradiated mushrooms (D2), etc. Once you are taking cod liver oil (over 1000 iu./15 ml), which is hardly a consistent Paleolithic source, you are replacing at dietary levels which are artificial.

As a source of Vitamin D3, whole body UV between 10 am and 1 pm for 20 minutes will give a D3 equivalent to oral dosing with 10,000 iu vitamin D3 (cholecalciferol). This is a rough estimate - it assumes you are outside only between March and October if north of 37 degrees latitude, and that you are unclothed and have average skin pigmentation where your minimal erythemal dose (MED) is 20 minutes. Black persons may need 5-6 times the exposure for the same dose. There is simply no natural food source that can compare to sunlight.

How much do you need and what is deficient?

Referencing the classical effects of D we might define insufficiency at less than 20 ng/ml and severe deficiency at 10 ng/ml. Current RDAs of 400 iu/day are based on avoiding rickets and were made before there was recognition of the other important effects of D. The dose-response curve for serum levels is highly non-linear, with each 5 ng/ml increment in serum levels requiring a larger increase in daily intake. Even 400 iu/day has been shown to be ineffective in treating osteoporosis. The non-classical effects of D seem to require larger levels to ensure health. Using a few facts we can come up with a more modern recommendation that is safe and reflects a more complete understanding of the importance of vitamin D.

1)   The level of 25(OH)D at which most dietary calcium intake is adequate (absorption is maximized) is 50 ng/ml

2)   The level of 25(OH)D that optimizes fracture prevention is about 40 ng/ml

3)   The level that causes PTH levels to plateau at a minimum (ensures no secondary hyperparathyroidism) is 40 ng/ml

4)   The level of oral D3 intake required to ensure a level of 40 ng/ml in most people is 4000 iu/day

5)   The highest reported level of oral intake that has never been associated with a case of hypercalcemia due to hypervitaminosis D is 10,000 iu/day

 

NOTE: The following section has been updated as of February 2011

Using the above numbers most of us who are not lifeguards would have D3 insufficiency, if not deficiency by the end of winter. I find that implausible and despite the epidemiology I believe megadosing with Vit D orally is unproven and unnatural.

I think it is reasonable to get some sun exposure up to but not exceeding the minimal erythemal doseIf you can get adequate sunlight at midday, say, sitting outside at lunchtime with 25% of your skin exposed for a half hourr, and your latitude and the season allow enough UV, you can use that as your source. Am I concerned about skin cancer or wrinkles? I think some sunning without burning is fine. I suspect what really trashes your skin are PUFAs and cigarettes, not the sun. If you worry about wrinkling, wear a broad-brimmed hat and get the sun on your arms and shoulders. 

Finally, don’t forget plenty of grass-fed butter or hard cheeses to get your K2.

NOTE: My standard disclaimer that this is not individualized medical advice applies here, only more so. If you take warfarin or other medications, or are otherwise not healthy, always consult your personal physician before taking any drug or dietary supplement.

 

References:

Vieth review AJCN

Garland review AJPH

Holick review AJCN

Holick and Chen Review AJCN

Willett fracture review JAMA

Rovner Review Archpediatrics

Cockayne Vit K and Fractures

Endocrine physiology Porterfield and White



 


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  • Response
    Response: Protein Bar
    There are a lot of good opinions here. Really gives me a new way of looking at things.

Reader Comments (33)

First, thank you for such a wonderful website. Is there any evidence that that increased VD intake will affect liver enzymes negatively? I just started 6,000 IUs daily and my liver enzymes shot up.

August 9, 2009 | Unregistered CommenterJim

Great post. This is the most useful summary I've seen on vitamin D. It's of great concern to me since I've resisted my doc's urging that I take massive calcium supplements (I'm a post-menopausal woman), even though I have no bone-density issues at present. I'm going to start doing the 20 minutes per day. I'm already doing the meat/butter/cheese (grass-fed when possible). Your post gave me the science to back up my intuitions. Thanks very much.

August 9, 2009 | Unregistered CommenterFelecia

Wow, this is the most in-depth post on Vit D I have ever read. One very important thing that people might want to keep in mind regarding Vit D3 supplementation: My husband and I were taking high dose Vit D3 for months and then got our levels tested. Imagine our shock when I test at 18ng and he at 19ng! Unbeknownst to us, our powdered Vit D3 capsules weren't being absorbed by our body. We've since learned that D3 is fat soluble, it needs to bind with fat in order to be absorbed. However the chances of this happening in the gut are obviously nil, as our tests showed. So now I buy our D3 in a gel cap bound with olive oil. No more deficiencies.

August 9, 2009 | Unregistered CommenterAilu

great post, kurt. i've been reading around about vitamin d, but you pulled it all together in a comprehensive and well-documented way. i just recommended to my partner that he read it, and yesterday we initiated a discussion of how these nutritional issues might be of relevance to our patients. the meds we prescribe often cause significant weight gain, independently raise the risk of diabetes, and so on. there are also some data about omega 3 deficiency being a contributor to affective illness. lots to learn, so much that it's a bit overwhelming but the fascinating data in combination with the obvious salience to health makes it all the more worthwhile.

August 9, 2009 | Unregistered Commenterjeff klugman

Excellent post as always. Do you have any guidelines for the Phoenecian sun? Is the "rough estmate" something you calculated from experience or can we plug in the variables ourselves?

August 9, 2009 | Unregistered CommenterGreg

Ailu, which brand of VD do you use? I did not know that it had to bind with fat.

August 9, 2009 | Unregistered Commenterstallion

Thanks for the post Kurt -- it's great to see a new one up here (I check every day), and this is an excellent + useful overview of Vit D. Plus a good motivator for me to actually get my 25(OH)D levels checked. I've been supplementing for a while at 5000IU/day but haven't actually calibrated these levels yet.

For those asking about Vit D pills, they do indeed need to be in "gelcap"/oil-based form in order to optimize absorption. I personally like the NOW Foods D3 gelcaps, which I've found to be the most competitively priced, both online and in my local stores. For whatever that is worth...

August 9, 2009 | Unregistered CommenterMark L

This post really brings it altogether for me. Thanks for being so thorough!

August 10, 2009 | Unregistered CommenterSteve P

I haven't seen Vitamin D in a gel or oil based form in Canada, but what I started doing with my tablets is crushing a few 1,000 mg pills and mixing them into soft-cooked egg yolks to eat.

August 10, 2009 | Unregistered CommenterMrs.K

Mrs. K, both Now Brand and Carlsons are oil based in gel caps and are available in the Toronto area (Ambrosia Natural Foods)

August 10, 2009 | Unregistered CommenterSteve P

Mrs. K and Steve P,
I just moved to Toronto from the states. I asked my doctor to do a VD test to check my levels and he said it was not medically necessary. Any advice?

August 11, 2009 | Unregistered CommenterJim

Good one, Kurt.

And it reminded me to get you on my blogroll, which is now done.

August 11, 2009 | Unregistered CommenterRichard Nikoley

Richard

Thank You. I hope your transition to the new host was seamless - the site looks great!

August 11, 2009 | Unregistered CommenterKurt G. Harris MD

Jim, If your doc won't order a Vit D test, you could go see a naturopath maybe, I think they would be more open to the idea of ordering the test without "evidence" of deficiency, but I don't know if they would be expecting that you would be a returning client or as augmenting your "traditional" health services... I've been thinking about doing this: (see website) http://www.grassrootshealth.net/
because apparently Canadians can participate.

August 13, 2009 | Unregistered CommenterMrs.K

Jim

Check out this site: http://www.vitamindcouncil.org/health/deficiency/am-i-vitamin-d-deficient.shtml

It is a home test kit that you can mail in. I am not vouching for their accuracy but it might be an alternative for you. I note their dosing protocol is similar to mine.

Greg

The solar irradiance guidelines are a guess. I think you can use the MED (minimal erythemal dose) as it should vary with sun intensity in a roughly linear fashion with UVB. I think that since burning happens sooner with more intensity or lighter skin, you can find out your MED and go just short of that. It is unlikely this would give you less than an adequate dose, and going to the point of burning and beyond will probably be of no benefit.

Your MED will lengthen if you tan - Nicole Kidman might start at 15 minutes and go to 20, good tanners might start at 25 minutes and go to hours to get the same dose. In my own case, in wisconsin, In May I sit out with my shirt off for about a half hour. Now that it is August, I sit out for about an hour to an hour and a half.

Jeff

I am really curious to know if D could mitigate any of the metabolic side effects of Zyprexa. Let me know if you find anything out.

Felicia

Calcium supplements without D don't work, and if you take enough D, supplementation might not be necessary.

Jim

Which liver enzymes? Transaminases?

Cholecalciferol (D3) in gel form should be mostly absorbed into the bloodstream via chylomicrons, bypassing the liver. Even if going through the portal vein, I can't think of a reason D would cause elevated liver enzymes.

A friend's son got a rash from a gelcap due to the fish oil - I've not hear of liver problems.

August 13, 2009 | Registered CommenterKurt G. Harris MD

you say about cod liver oil that it is a "hardly a consistent Paleolithic source" but endorse vit d supplementation with pills - wouldn't it be more logical to think of oil as more "paleolithic" than some artificially produced chemicals?

August 13, 2009 | Unregistered Commenternanashigonbei

nana

I don't see your point - I was pretty clear about the sun being the best source.

If you prefer chugging lots of fish oil instead of taking oil containing capsules to make up for your D deficiency, go ahead - neither was a paleolithically available food source in most places and times in the past.

PaNu is not a religion and I say repeatedly it's not about food re-enactment. It's about metabolism.

BTW - whether a chemical is naturally occurring and extracted, or synthesized in a laboratory is totally irrelevant to its efficacy or whether it is healthy. I don't look askance at big pharma drugs because they are manufactured or unnatural, but because most of them are dangerous or don't work.

August 14, 2009 | Registered CommenterKurt G. Harris MD

Hi Kurt,
Nice website. A picture of Suzuki Roshi linked to caloric restriction. He was a great man. Have you read his book "Zen Mind,Beginner Mind?" I knew him long ago and actually he could eat like a horse. In soto zen however monks do go on retreats and fast.
I bet we have alot in common. Please email me.

August 14, 2009 | Unregistered Commenterhomertobias

Wonderful post Dr Harris. I'm new to your blog but have already bookmarked it as one of my favorites. Vitamin D is a very pertinent topic in the paleo community and a subject I have long been interested in knowing more about. Along with the info on vitamin D over at freetheanimal.com, this post contained some of the most complete and accessible info on vitamin D that I have come across on the web. One question though: I plan on beginning Vitamin D replacement this fall/winter (4,000 iu per day in Duluth, Minnesota). Do I need to begin taking the tablets before my sun exposure becomes limited, say before mid October, or will the 2 month carryover of vitamin D from my sun exposure during the summer and fall last me until the D from the tablets kick in?

Thanks,

Mikie K

August 14, 2009 | Unregistered CommenterMikie K

Hi Kurt,

This post was worth the wait... Spectacular!! Keep up the strong work! I like your phrases... em2... panu... I think you are very articulate and inventive!! Thank you for bringing your evo bio background to understanding mammalian systems and achieving optimal functioning. I am never surprised now how so many 'Renaissance' men and women exist in the Paleo blogosphere...

-G

August 14, 2009 | Unregistered Commenterg

Thanks for taking time out of your obviously busy schedule to write these articles, Dr Kurt.

For the Canadians: I've been using D-Drops. It's exactly what it sounds like: liquid vit D supplement in a dropper bottle. I've seen it at all the big drug stores and nutrition shops: Shoppers Drug Mart, Zehr's/Superstore, etc. I've been tested by the grassrootshealth.net people and my 25OH-D was at 77 back in March, so I'm confident that the D Drops are good.

August 14, 2009 | Unregistered CommenterKristine

I would like to share Cedric Garland's theory of another mechanism of action of Vitamin D. Low vitamin D is associated with the breakdown of your intracellular tight junctions. There are many types of intracellular tight junctions, most of which are involved in allowing communication between adjacent cells in your body. For example, a breast cell talks to its neighbors via its tight junctions. Prolonged lack of communication from damaged tight junctions can lead a breast cell to de-evolve. These isolated more primitive breast cells then do what many single cell organisms do.....they multiply. They lack the normal feedback mechanism that inhibits unbridled replication also mediated through tight junctions. They also lack cohesiveness and are prone to break off and, you guessed it, travel to the closest lymph node. Voila, you have a breast cancer.
Now we all make cancers, you may have one or two brewing right now. Usually what happens is that our tumor suppressor genes eliminate them before they become "clinically relevant". Genetic defects in tumor supressor genes (BRCA 1 & 2 for example) lead to dramatically increased rates of clinically relevant cancers. What is nice is that Vitamin D works for BRCA 1 or 2 carriers as well.... better tight junctions, better intracellular signalling, beter intracellular cohesiveness, less tumorogenesis, less work for damaged tumor suppressor genes to do.
Now lets look at leaky gut syndrome and how vitamin d might interplay with gluten grain damage to promote or suppress autoimmune disease. The basic theory here runs as follows. You host more bacteria in your intestines than you have cells in your body with your own DNA signature. With a good diet, they are mostly friendly bacteria. Lining your intestine are a long line of very important very metabolically active cells. These cells constantly have to determine what is food, (let it in), what is good bacteria (nourish them, but don't let them in), and what is bad bacteria or food poisin (don't let them in, try to push them on through, inhibit their growth). You renew your brush border cells every 4 days. Leaky gut is a damaged brush border. It is letting in both good and bad bacteria which don't belong in your body. This overwhelms your immune system which constantly has to kill this proteus bacteria or that klebsiella. Then your exhausted immune system goofs....a portion of a proteus looks a whole lot like a pancreatic beta cell. So your own immune system attacks your pancreas and you have Type 1 diabetes.
Back to tight junctions. How did those pesky pieces of bacteria get in? Between the intestinal luminal cells perhaps? You bet. Gluten is a little different. It primarily damages the brush border on the innerfacing edge of these cells, it doesn't break down the connections between them. Then you can't absorb much of anything nutritious, Celiacs can be thin or fat, but many get anemic because they can't absorb iron, have early osteoporosis because they can't absorb calcium and, you guessed it, have a host of autoimmune diseases because they can't absorb vitamin d and then lose their intestinal tight junctions.

August 15, 2009 | Unregistered Commenterhomertobias

Hi Kurt,

I just discovered your blog and am really enjoying it. I have been on a Paleo low carb diet for just over three years now after I discovered I was intolerant to grains and dairy. I also have osteoporosis and untypical diabetes type 2 (I'm thin and not insulin resistant). I've been supplementing with vitamin D3 for about 18 months but I get above normal levels of 25(OH)D very easily. After I was on 4,000 IU D3 per day for about four months during the winter before last my 25(OH)D level measured 384 nmol/L (154 ng/dl) so I had to stop D replacement for several months till my endocrinologist told me to start again at 2,000 IU per day. Then I had another test the other week and my 25(OH)D is up to 250 nmol/l (100 ng/dl) and my alkaline phosphatase levels are also just slightly above normal....sigh. It's very difficult for me to get this just right ! I don't have any vitamin D hypersensitivity and I hardly get any sun living in the UK where it is often cloudy.

Btw, I am prescribed Strontium Ranelate for my osteoporosis which is much better than a bisphosphonate !

Anne

August 15, 2009 | Unregistered CommenterAnne

Mikie

The best estimate of half life is about 2 months, so I would start oral supplementation as soon as you are no longer getting sun - no reason to let your levels drop

G and Kristine

Thank You

Anne

My recommendations apply only to those not taking any drugs that affect bone metabolism like bisphosphonates or strontium. You should continue to work closely with your endocrinologist.

Homer

Yes I've read ZMBM several times. Hard to take vows if you are carnivore, I suppose. Don't buy the metaphysics, but can be good for your mental health.

I've read several Garland papers including the review I cited. I think the anti- autoimmune effects of D are mediated in several ways, including upregulation of zonulin and effects on lymphocytes. I would not trust D to protect me from gialdin protiens, but it may help some.

August 15, 2009 | Registered CommenterKurt G. Harris MD

I'd forgotten the "no meat" part of zen macrobiotics. But then I was an adolescent when I sat at ZCSF and did retreats at Tassajara. My take is that we are much better off being omnivores than either herbivores or strict carnivores. I do remember working in the garden and the kitchen growing vegetables organically and eating whole foods. My first college degree was in History of Consciousness and comparative religion. I like the metaphysics, I even taught Zen Buddism at one point, lived in a zen center while at Yale University School of Medicine. Then residency.....you know, the reality of sleep depravation in a busy county hospital. I haven't thought of Suzuki Roshi in years and then there he was on your blog. Thank you.

August 18, 2009 | Unregistered Commenterhomertobias

Hmm. Are you saying that damage to the skin from PUFAs and smoking is more harmful than the sun, or that the sun doesn't really age the skin? I thought there was wide agreement that photodamage is responsible for the overwhelming majority of exogenous skin aging. Plus, even hunter-gatherers have wrinkles (actually, even more wrinkles than "unhealthy Westerners" -- which I put down to sun avoidance). Without supplements, I think there's a tradeoff between vitamin D3 levels and skin wrinkling. I'll be reading your upcoming post with interest.

As a side note, I've been taking 5,000 IU of vitamin D3 for a few months and my serum level is 45 ng/mL. That seems like a fairly consistent result compared with what others have posted here. Living in the north and having avoided the little sun we have due to fair skin, I can only imagine how badly deficient I've been for most of my life. Well, better late than never.

- JLL

August 19, 2009 | Unregistered CommenterJLL

JLL

See this - http://www.paleonu.com/panu-weblog/2009/8/19/how-much-sun.html

You should probably bump up to 8000 iu and test again in 2 months.

August 19, 2009 | Registered CommenterKurt G. Harris MD

Kurt,

I've tried three different Vit D supplements. The first was a chalky white tablet. I found this caused me to feel nauseous and left a metallic taste in my mouth, so I stopped. Then I tried a soft gel cap and that made me feel short of breath. Then I tried another brand of soft gel cap and that was toxic again, giving me a bad taste in my mouth. They were all at the 1000IU level. Any idea as to what is going on and what I could take instead?

David

August 26, 2009 | Unregistered CommenterDavid

Hi
Interesting article. After I found using dietary software a couple of years ago i could not get enough vitamin D I start reviewing the literature and reached similar conclusions to yours here. It seems that the stop skin cancer campaign has been so effective that it has even impacted the dermatology profession itself.

My diet is Loren Cordain style paleo, with a little dairy fat, in my sunbaking campaign last summer I noted that it seemed to be a lot more diifficult to burn than when I was younger and I think you have hit the nail on the head regarding dietary fat and susceptibility to sunburn.

Keep up the good work.
OB

September 1, 2009 | Unregistered Commenterob

You wrote that higher Vitamin D could allow a greater tolerance of carbohydrates. This makes sense from a Paleolithic perspective. Sunlight and therefore Vitamin D is the highest in the summer time, and this is when seasonal fruit with its higher carb content is available.

October 30, 2009 | Unregistered CommenterMatt Metzgar

Hi Dr. Harris,

Great article on vitamin D! I did want to note a minor measurement typo re: 25 (OH) D assay levels - ng/dl should be ng/ml.
Thanks!

Rikki

Thanks, I'd be shocked if that were the only typo! I shall correct it and review all the D posts.

November 8, 2009 | Unregistered CommenterRikki Keen

Dr. Harris,

Do you foresee problems with me taking D3 at night with my evening meal? I know it would make sense to take during the time the sun is out... but I'm not hungry till the evening.

It doesn't seem to mess with my sleep, like I've read on Nephropal, and I assume it's best to take it with fat since its a fat soluble vitamin (don't take it without food?)

I take the NOW brand if it makes any difference.

Thanks Dr. Harris.

KGH:

Should be fine to take it any time. Per the post on dosing, it is not all converted to 25 D at once.

November 10, 2009 | Unregistered CommenterDanny

I'll reread that post. Thank you Dr. Harris!

Btw, I can't thank you enough for your "getting started" section. I refer my coworkers to it all the time.

November 11, 2009 | Unregistered CommenterDanny Roddy
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