If I described a substance with the following properties, what would you guess it was?-It's synthesized by the body from cholesterol
-It crosses cell membranes freely
-It has its own nuclear receptor
-It causes broad changes in gene transcription
-It acts in nearly every tissue
-It's essential for health
There's no way for you to know, because those statements all apply to activated vitamin D, estrogen, testosterone and a number of other hormones. Vitamin D, as opposed to all other vitamins, is a steroid hormone precursor (technically it's a secosteroid but it's close enough for our purposes). The main difference between vitamin D and other steroid hormones is that it requires a photon of UVB light for its synthesis in the skin. If it didn't require UVB, it would be called a hormone rather than a vitamin. Just like estrogen and testosterone, it's involved in many processes, and it's important to have the right amount.
The type of vitamin D that comes from sunlight and the diet is actually not a hormone itself, but a hormone precursor. Vitamin D is converted to 25(OH)D3 in the liver. This is the major storage form of vitamin D, and thus it best reflects vitamin D status. The kidney converts 25(OH)D3 to 1,25(OH)D3 as needed. This is the major hormone form of vitamin D. 1,25(OH)D3 has profound effects on a number of tissues.
Vitamin D was originally identified as necessary for proper mineral absorption and metabolism. Deficiency causes rickets, which results in the demineralization and weakening of bones and teeth. A modest intake of vitamin D is enough to prevent rickets. However, there is a mountain of data accumulating that shows that even a mild form of deficiency is problematic. Low vitamin D levels associate with nearly every common non-communicable disorder, including obesity, diabetes, cardiovascular disease, autoimmune disease, osteoporosis and cancer. Clinical trials using vitamin D supplements have suggested that it may protect against cancer, hypertension, type 1 diabetes, bone fracture and enhance athletic performance. However, the evidence is pretty thin for most of these effects and requires more research.
It all makes sense if you think about how humans evolved: in a tropical environment with bright sun year-round. Even in many Northern climates, a loss of skin pigmentation and plenty of time outdoors allowed year-round vitamin D synthesis for most groups. Vitamin D synthesis becomes impossible during the winter above latitude 40 or so, due to a lack of UVB. Traditional cultures beyond this latitude, such as the Inuit, consumed large amounts of vitamin D from nutrient-rich animal foods like fatty fish.
The body has several mechanisms for regulating the amount of vitamin D produced from sunlight exposure, so overdose from this source appears to be impossible. Sunlight is also the most effective natural way to obtain vitamin D. How much vitamin D is optimal? 30 ng/mL 25(OH)D3 is required to normalize parathyroid hormone levels, and 35 ng/mL is required to optimize calcium absorption. It's probably best to maintain at least 35 ng/mL 25(OH)D3.
Here's how to become vitamin D deficient: stay inside all day, wear sunscreen anytime you go out, and eat a low-fat diet. Make sure to avoid animal fats in particular. Rickets, once thought of as an antique disease, is making a comeback in developed countries despite fortification of milk (note- it doesn't need to be fortified with fat-soluble vitamins if you don't skim the fat off in the first place!). The resurgence of rickets is not surprising considering our current lifestyle and diet trends. In a recent study, 40% of infants and toddlers in Boston were vitamin D deficient using 30 ng/mL as the cutoff point. 7.5% of the total had rickets and 32.5% showed demineralization of bone tissue! Part of the problem is that mothers' milk is a poor source of vitamin D when the mother herself is deficient. Bring the mothers' vitamin D level up, and breast milk becomes an excellent source.
Here's how to optimize your vitamin D status: get plenty of sunlight without using sunscreen, and eat nutrient-rich animal foods, particularly in the winter. The richest food source of vitamin D is high-vitamin cod liver oil. Blood from pasture-raised pigs or cows slaughtered in summer or fall, and fatty fish such as herring and sardines are also good sources. Vitamin D is one of the few nutrients I can recommend in supplement form. Make sure it's D3 rather than D2; 2,000 IU per day hould be sufficient to maintain blood levels in wintertime unless you are obese (in which case you may need more and should be tested). Vitamin D3 supplements are typically naturally sourced, coming from sheep lanolin or fish livers. A good regimen would be to supplement every day you get less than 10 minutes of sunlight.
People with dark skin and the elderly make less vitamin D upon sun exposure, so they should plan on getting more sunlight or consuming more vitamin D. Sunscreen essentially eliminates vitamin D synthesis, and glass blocks UVB so indoor sunlight is useless. Vitamin D toxicity from supplements is possible, but exceptionally rare. It only occurs in cases where people have accidentally taken grotesque doses of the vitamin. As Chris Masterjohn has pointed out, vitamin D toxicity is extremely similar to vitamin A deficiency. This is because vitamin A and D work together, and each protects against toxicity from the other. Excess vitamin D depletes vitamin A, thus vitamin D toxicity is probably a relative deficiency of vitamin A.
I know this won't be a problem for you because like all healthy traditional people, you are getting plenty of vitamin A from nutrient-dense animal foods like liver and butter. Vitamin K2 is the third, and most overlooked, leg of the stool. D, A and K2 form a trio that act together to optimize mineral absorption and use, aid in the development of a number of body structures, beneficially alter gene expression, and affect many aspects of health.
Thanks to horizontal.integration for the CC photo.
40 comments:
Your blog is such a great source of knowledge, Stephan!
Any thoughts on K2 dosing? I've learned of the importance of D3 and A in the past, but am now just learning of K2 thanks to this blog.
Hi Scott,
The best dose would be the amount you can get from a K2-rich diet. Goose liver is the richest source tested since Price and it contains 369 micrograms K2 MK-4 per 100g. That would be a big serving of foie gras though. Grass-fed butter was the richest source according to Price, but no one has tested it in recent times so we don't have any numbers.
My best guess is that 100-300 micrograms from all sources would be a rich daily K2 intake. Note that that dose is less than 1/150th of what's found in many supplements. 45 milligrams K2 MK-4 was used in a number of bone density trials, and seems to be well tolerated so that's what many supplements use. I wouldn't take a dose that large myself because I don't think you could get anywhere near that with food.
I do sometimes use the Thorne supplement which is 1 milligram per drop. I'll put one drop in a dish that I'll be eating for several days. More often than not, I'll skip the supplement and just eat my grass-fed butter.
It's interesting how diseases of civilization are linked to different aspects of "civilized" lifestyle such as eating processed foods and staying indoors too much. It's a good argument for a holistic view of healing.
4,000- 5,000 IU of D per day is quite a bit more than I had assumed (with no real reference) to be ideal. I am not quite sure how I would approach that range. I'm just not in the sun enough and a cloudy winter is fast approaching.
From dietary sources 4,000- 5,000 IU of D per day would require, say, 1 1/2 lbs of sockeye salmon or an unfathomable amount of eggs (as in hundreds of them).
Currently I have two different types of cod liver in my refrigerator (Carlson and Country Life) and in each bottle, for every unit of Vitamin D, there is 3 to 10 times as much Vitamin A. I am not sure where the current science is on Vitamin A toxicity, but taking the extreme scenario here, I imagine it may not be ideal to supplement 50,000 IU of Vitamin A a day...I just looked it up and according to the National Academy of Sciences set Tolerable Upper Intake Levels (in 2000), the max for an adult is 3,000 mcg (10,000 IU) of A a day.
P,
Carlson and other common brands of CLO are low in vitamin D because it's removed during the processing steps. I always recommend high-vitamin cod liver oil because it has a balanced amount of A and D. Green Pastures is a good brand, but you have to order it. It's cheaper per dose than Carlson's even though it's better quality.
It is difficult to get 4-5,000 IU a day from food, as you pointed out. I don't think it's absolutely necessary to take that much. If your tank is full from summer sun, you can probably maintain an adequate serum level with a lower intake of D, say 2,000 IU a day for a few months.
If you live far North like in Canada, it might be wise to supplement in the winter unless you're eating large amounts of D-rich marine food every day like the Inuit.
Reid,
I agree. Reductionism isn't going to get us very far when health is so complicated.
Ok, but I live in sunny San Diego (lat-32-33), eat a non-SAD diet that must be comparatively pretty rich in vit D (as far as D3 in food goes); I have light skin and don't tan much; don't use sunscreen nearly as liberally as I used to; and for a year or so I have made a concerted effort to get some more daily UV exposure. I'm not stuck in a office but I do spend a lot of time indoors with varying amounts of time outdoors.
But I still wasn't getting my 25 (OH) D3 levels out of the lower 40s (ng/mL) with either 2000 iU D3 daily (less sun exposure) -44 ng/mL or more summer sun without supplementation - reduced my level to 40 ng/mL. And i'm not elderly, but I'm not a spring chicken anymore, at 46 yo ;->.
I don't see any other way to get to "normalized" 55-65 ng/mL 25 (OH) D3 levels without supplementing at least 4,000-5,000 iU a day, which is what I'm doing (for my husband, too, though he hasn't been tested. I'll test again in late winter or early spring. I found 2,500 and 4,000 iU doses of D3 (to reduce the capsule 3s), but what I find most convenient are Carlson's D3 drops at 2,000iU dose, which I put on food or in a creamy beverage.
Everyone I know locally (San Diego are) who has been tested had 25 (OH) D3 levels even lower than mine, usually in a truly deficient range. So unless one is very young and still producing a lot of the D3 hormone precursor from UV exposure, a lifeguard, or literally bathes in the sun at midday, AND makes an effort to eat Vit D3 rich foods (a very small minority, I don't think supplementation should be written off.
I do like the idea of the high vitamin CLO, which is more like food, but every vitamin shop and dept near me sells the kind with the vitamin levels reduced, but that specialized CLO requires ordering, is a lot more expensive, and isn't as easy to dose and take as capsules or drops, especially for the other members of the family. There is one nutrition counselor I know of who stocks the Green Pastures CLOs but naturally, with a hefty markup.
I can't really come up with bad reason to use capsules or drops, unless there is something I'm missing.
Hehe, the word verification is frousnit :-).
Excellent post as ever Stephan. I do not know where you find the time (-:.
You prompted me to look up commercial lard.
Commercial lard has a very different profile, and is almost devoid of minerals and vitamins, and has a very poor Omega 3:6 profile.
It reinforces to what an extent we are denuding `food` of nutrients - and presumably with the blessing of nutritionists etc.
It is a crazy crazy world.
http://www.nutritiondata.com/facts/fats-and-oils/483/2
Robert Brown
Author
Omega Six The Devils Fat
www.Omegasixthedevilsfat.com
Excellent information!
(but why are you bringing back the old vitamin-D deficient 'pale' pict? b/c it suits the topic at this time of the year? how about the 'tan' the island shot??)
*hee*
I've cranked up my vitamin D 4000 IU daily now (or if I skip a few days -- a handful).
NOW just came out w/ a great 5000 IU strength capsule too.
-G
Anna,
I have a couple of thoughts. First of all, 40 ng/mL is pretty good. The fact that you couldn't get it higher than that with regular sun exposure on pale skin suggest to me that either the lab test is reading low or maybe that's your body's preferred equilibrium point. I believe Dr. John Cannell of the Vitamin D council says that different lab tests give different results and some are better than others.
The Green Pastures high-vitamin CLO is actually cheaper per dose than Carlson's and the other grocery store brands because it contains 90 doses (1/2 tsp). It ends up being 25 cents per dose. I send out a mass e-mail to my friends and buy a bunch so I save on shipping. It's actually a bit cheaper if you buy from Live Superfoods than from Green Pastures directly.
The other nice thing about CLO is it's vitamin A content. That way you will never have a relative excess of D over A. Of course, if you eat liver and other A-rich foods, that's not a problem.
Robert,
If you get "leaf lard", which is the visceral fat, it has a better fat profile. Only 8% PUFA, and the n-6/3 ratio will depend on how the pig was raised. I would expect it to be mostly n-6 in most cases. Here's the nutritiondata page for leaf lard:
http://www.nutritiondata.com/facts/pork-products/2194/2
G,
I swapped back to the ghostly photo just in time for winter! I actually prefer this photo because it shows my face, but previously Blogger would delete it periodically due to some glitch so I stopped trying.
Hi Stephan,
Have you had a chance to look at the book review at the Modern Forager blog? Fat: An Appreciation of a Misunderstood Ingredient with Recipes by Jennifer McLagen (she also authored Bones a while back, which I also have and enjoyed).
I've loving this book!
Anna,
Yes, I've read that. It's a nice book. I may get a chance to meet the author later this year.
Stephan, regarding K2, I'm using the green pastures butter oil caps, which I think is a half-gram each. I take two per day, along with CLO.
But, any idea how much actual K2 that entails? I saw your comment over on my blog about just one drop of the synthetic K2 over several days. I've got like three bottles of the Green Pastures left, in the fridge. It is rather expensive and if I'm taking too much I could extend it.
Also, are you convinced that the synthetic is equivalent in terms of benefit?
Hi Richard,
I don't know how much K2 the butter oil contains. Green Pastures uses the same quinone test Price used, which is by nature not very quantitative. So they can say it contains plenty of K2, but not the specific amount.
If grain-fed butter contains 15 micrograms per 100g, then grass-fed might contain up to 750 micrograms per 100g (if Price was right that the relative amounts in butter differ by up to 50-fold). Let's assume the butter oil is 5X concentrated relative to butter. I have no idea whether that's true, but I'll assume it for the sake of this calculation.
Then butter oil would be 3.8 mg per 100g. That comes out to (max) 76 micrograms per half teaspoon. When I use the Thorne supplement, I'm typically getting about 333 micrograms per day. Maybe I'll reduce it now that I see that it's probably higher than the butter oil supplement. It's just hard to subdivide a drop!
I agree with you that the butter oil is expensive. That's why I tested the Thorne product. It's incredibly cheap if you use it at the dose I do. My impression is that I see the same changes on my skin with the Thorne supplement that I saw with the butter oil. If you end up trying it, please let me know if you see the same effects on your dental plaque that you see with the butter oil.
I'm generally wary of synthetic and isolated supplements, and that also applies to the Thorne product. All I can vouch for is that it has similar effects on my skin as butter oil, and that it's well tolerated up to 45 mg/day in clinical trials. If it cost the same, I'd definitely recommend the butter oil because it's closer to food. And butter has a long history of safe use, whereas synthetic MK-4 doesn't.
So that's how I feel. I'm not going to recommend one over the other at this point, I'll just lay out the pros and cons and let people make up their own minds.
Thanks, Stephan.
Amazing we have to be so speculative, employing so much guess work for something so profound.
In my life, I have never eaten anything that has delivered the profound effects, so quickly, as the butter oil.
This company also has very good prices on Green Pastures products:
http://www.building-health.com/weston-price-inspired-c-1.html?zenid=4f4e3b041724dabcc540828d8f18462e
Meighen
Re: K2-- The best source of natural K2 is from Natto, which tastes terrible (it's fermented soy). If you're going to dose K2, there is one major study done in Rotterdam using K2 from Menaquinone which demonstrated that a dose of approximately 40 mcg per day was effective. There is one other major study which was done on K2 in Japan which used doses at a much, much higher level which proved effective against osteoporosis. The reason the dosing was so much higher was that the K2 use was a different form (Menatetranone) which has a half-life of about 3 hours only. Both forms peak in your bloodstream at about 1 hour, but the Menaquinone form of K2 has a half-life of about 36 hours, so it will effectively keep working far longer and will allow you to build serum levels if you dose 40-100 mcg every 24 hours.
Solgar makes a form of K2 from Natto, and it's pretty cheap and widely available.
Jerry,
The Rotterdam study was an observational study, and they didn't distinguish between different forms of menaquinones. MK-4 was probably more abundant than MK-7 in that study, because most of the menaquinone came from dairy.
Most of the cardiovascular research that has been done on K2 was with MK-4 rather than MK-7. Same with the osteoporosis studies. It remains to be seen whether MK-7, produced by bacterial fermentation, has the same effects as MK-4, which is produced by mammals, for mammals. I think it's unlikely, given the fact that MK-7 is metabolized differently than MK-4.
If MK-7 is better, why do our own bodies make MK-4, and why do animals from fish to mammals synthesize MK-4 for their young in eggs and milk?
I'm beginning to think that my breast cancer was caused by low vitamin D levels. I was tested last fall, as part of a bone density panel, and my level was <4. I guess that means it was lower than their scale. After supplementing with prescription D, 50K iu per week, for six weeks, the level was up to 20. In this post, you only touch on the K2. Is this something that might help me to get my D levels back to normal? I'll probably start going to a tanning place this week (have a cruise in March anyway), to try to get some UVB during the winter. I am obese and have had all kinds of problems since putting on this weight about 15 years ago. Should I be taking the K2 too?
I'm beginning to think that my breast cancer was caused by low vitamin D levels. I was tested last fall, as part of a bone density panel, and my level was <4. I guess that means it was lower than their scale. After supplementing with prescription D, 50K iu per week, for six weeks, the level was up to 20. In this post, you only touch on the K2. Is this something that might help me to get my D levels back to normal? I'll probably start going to a tanning place this week (have a cruise in March anyway), to try to get some UVB during the winter. I am obese and have had all kinds of problems since putting on this weight about 15 years ago. Should I be taking the K2 too?
Birdwatcher,
Wow, that is low vitamin D! I think you're doing the right thing trying to bring it up. Overweight people require more to get their blood level up, so don't be discouraged.
The 50K D supplement, was it D2 or D3? If it was D2, as I suspect it was, you should fire your doctor. D3 is the only form you should be taking, it's the kind your skin makes using UVB and it's far more effective than D2, which is not natural in large amounts.
Don't worry about supplementing K2, just eat your pastured butter and organs.
I think the received wisdom is wrong about vitamin D
It all makes sense if you think about how humans evolved: in a tropical environment with bright sun year-round.Yes, but modern humans entered and began to evolve by natural selection to the conditions of northern Europe, (where there is no UVB/vitamin D synthesis for several months of the year), 30,000 years ago. If vitamin D was in short supply the first adaptation would be to synthesize as much as possible and store it for the winter.
But north Europeans don't do that, they shut off synthesis after 20 minutes sunshine on exposed skin which provides an average of 20,000 IU of vitamin D with full body exposure. So what? Well that's no more than Black Africans - who'll take 2hrs. 30,000 years of natural selection didn't alter the amount of this vital secosteroid they synthesized during the summer despite the fact that they, unlike Africans, have to go several months without the UVB.
Even in many Northern climates, a loss of skin pigmentation and plenty of time outdoors allowed year-round vitamin D synthesis for most groups. - In Britain and most of northern Europe there is at least 1 month without.
Jablonski/Chaplin map p.12
Vitamin D can be stored The Pharmacology of Vitamin D"During summer, we accumulate vitamin D3 and store it, so that supplies for vitamin D do not become completely depleted during the winter months."
If 30,000 years after entering northern Europe natural selection hasn't changed this (as it easilly could). I wonder if the reason isn't that the Vitamin D requrements are met, and then some, by North European sunshine.
"If one looks at the system of vitamin D metabolism in Figure 2 from the perspective of a system
designed to control something, it becomes clear that this is a system better designed to cope with an abundance of supply, not a lack of it".
This points towards a natural homeostasis of vitamin D synthesis and storage in northern Europe that has not modified from the one evolved in Africa because it's still dealing with an excess.
Trevor Marshall may be on to something-
"that the observed serum levels are modified by disease processes—is far more plausible than the currently accepted ‘vitamin’ pragma—that the lower levels observed in sick individuals are indicative of a nutritional deficiency. [...]
What is a ‘natural’ homeostasis of
vitamin D synthesis?
It is thus very difficult to find a population which can be studied in order to ascertain what the level of natural metabolic homeostasis for 25-D might actually be. These studies show a wide variation in levels of 25-D being generated by populations whose diets have probably not yet
been significantly altered by ‘The Sunshine Vitamin,’ indicating
that the unsupplemented metabolic homeostasis is probably in
the range 23–60 nmol/L, and that it falls with advancing age."
(From Vitamin D Council website)
"When researchers went to an Italian nursing home, they found that 99 of 104 residents had no detectable vitamin D in their blood,". Bad news for these people?
"All of the 104 resident were over 98 years old!". And if they'd spent decades topping up their vitamin D levels with pills to maintain 'normal' levels?
It probably does not do any harm to take thousands of IU of vitamin D, for a year or two at least, but that's because "this is a system better designed to cope with an abundance of supply, not a lack of it".
Ken,
The fact that high levels of vitamin D are important is underscored by the fact that humans rapidly depigmented as they migrated North.
Indoor living is an evolutionary novelty. When you're a hunter-gatherer or a subsistence farmer, you spend a lot of time outdoors. One month without sunlight will not deplete vitamin D levels much if you start out vitamin D replete from spending a lot of time outdoors. Add to that a diet rich in animal food and especially seafood, and you would have no problem maintaining high levels of D for a month without UV.
When you get to extreme northern climates like scandinavia and greenland, of course much of the year will pass without UV. I think it's instructive that the Inuit had a relatively high dietary intake of vitamin D from oily marine foods. Probably not optimal but it was about all they could squeeze out of their environment.
Vitamin D insufficiency defined as serum 25-OHD concentration <40 nmol/l was detected in 78% of group A, 83% in group B and 76% in group C, respectively.
Hypovitaminosis D is common in both veiled and nonveiled Bangladeshi women. It might be suggested that unleavened bread is responsible due to the well known fact that "cereals seem to increase vitamin D requirements by decreasing calcium absorption and by shortening the half-life of the main blood metabolite of vitamin D"
Staffan Lindeberg Cereal grains
But surely non-veiled women would be getting more UVB and eating less traditional food. I think this is a telling bit of evidence that the ‘natural’ homeostasis of
vitamin D synthesis (i.e. without ingested 'D') is lower than the received wisdom
Effects of Above Average Summer Sun Exposure on Serum 25-Hydroxyvitamin D and Calcium Absorption"In his 1999 review [linked to in my last comment-Ken], Vieth (11) notes that serum 25(OH)D levels above 200 nmol/liter are not rare among healthy persons with ample sun exposure. Of the 30 outdoor workers in whom we measured 25(OH)D in late summer, 3 had levels above 200 nmol/liter (i.e. 211, 205, and 203 nmol/liter); their sun exposure occurred in Nebraska, Kansas, and North Dakota, at 41.2°, 39.0°, and 46.8°N latitude, respectively".
46.8 °N sounds about right for northern Europe now clearly this guy had a higher than average limit on vitamin D synthesis; instead of stopping at 20,000IU his exposed skin made two or three times that. What I think this shows is it's the limit on vitamin D synthesis that is the most important factor. Natural selection would have made people like him the majority if it was trying to maximize vitamin D production. He is somewhat unusual for his limit on vitamin D synthesis not for his white skin .
"Based on the average rate of decline observed in our subjects, it can be estimated that in individuals for whom summer sun exposure is the principal source of vitamin D, a late summer 25(OH)D level of approximately 127 nmol/liter is needed to avoid levels falling to less than 75 nmol/liter by late winter."
But with a higher synthesis limit everyone could have those levels so why didn't evolution give them to humans in northern Europe?
It can only be because the actual average levels of 25(OH)D are as high as they can be without reducing overall fitness.
Over the last 3 years, I have learned a great deal about vitamins A, B12, D3, and K2 from various sources, but mostly from Dr. Mercola's website, so I advise people to spend an hour watching his recent video on vitamin D3, appearing below. Also enter: "vitamin K2" in their searchbar.
FREE Vitamin D Lecture
He states: "I summarize the mountain of recent scientific evidence supporting that understanding how to take advantage of vitamin D is one of the most important physical steps you can take in your health."
http://articles.mercola.com/sites/articles/archive/2008/12/16/my-one-hour-vitamin-d-lecture-to-clear-up-all-your-confusion-on-this-vital-nutrient.aspx
Compare the vitamin K2 content of various foods at: http://www.westonaprice.org/basicnutrition/vitamin-k2.html#fig4
thank you for this excellent article. What do you suggest for vegetarians or vegans? And what is the connection to hypothyroid?
Turtlewolf,
Vitamin D supplements are vegetarian, as they come from a by-product of the wool making process. As for vegans, I can't think of any good alternative to sunlight.
Why are Europeans white?
"There are several problems with the vitamin-D hypothesis. First, if lack of this vitamin created the selection pressure that led to white European skin, why are Europeans genetically polymorphic in their ability to maintain blood levels of vitamin D? At least two alleles reduce the effectiveness of the vitamin-D binding protein, and their homozygotes account for 9% and 18% of French Canadians (Sinotte et al., 2009). If lack of this vitamin had been so chronic, natural selection would have surely weeded out these alleles."
Vitamin D and aging.
"Taken together, aging shows a U-shaped dependency on hormonal forms of vitamin D suggesting that there is an optimal concentration of vitamin D in delaying aging phenomena. Our recent study shows that calcidiol is an active hormone. Since serum calcidiol but not calcitriol is fluctuating in physiological situations, calcidiol might determine the biological output of vitamin D action. Due to its high serum concentration and better uptake of calcidiol-DBP by the target cells through the cubilin-megalin system, calcidiol seems to be an important circulating hormone. Therefore, serum calcidiol might be associated with an increased risk of aging-related chronic diseases more directly than calcitriol. Aging and cancer seem to be tightly associated phenomena. Accumulation of damage on DNA and telomeres cause both aging and cancer, moreover the signalling pathways seem to converge on tumour suppressor protein, p53, which seems to be regulated by vitamin D. Also, the insulin-like growth factor signalling pathway (IGF-1, IGFBPs, IGFR) and fibroblast growth factor-23 (FGF-23) regulate growth, aging and cancer. Vitamin D can regulate these signalling pathways, too. Also NF-kappaB and telomerase reverse transcriptase (TERT) might be molecular mechanisms mediating vitamin D action in aging and cancer. Calcidiol serum concentrations show a U-shaped risk of prostate cancer suggesting an optimal serum concentration of 40-60 nmol/L for the lowest cancer risk.
Premature aging in vitamin D receptor mutant mice.
"Overall, VDR KO mice showed several aging related phenotypes, including poorer survival, early alopecia, thickened skin, enlarged sebaceous glands and development of epidermal cysts[...]Unlike the wildtype controls, VDR KO mice lose their ability to swim after 6 months of age. Expression of all the genes was lower in old VDR KO mice, but only NF-kappaB, Fgf-23, p53 and IGF1R were significantly lower. Since the phenotype of aged VDR knockout mice is similar to mouse models with hypervitaminosis D(3), our study suggests that VDR genetic ablation promotes premature aging in mice, and that vitamin D(3) homeostasis regulates physiological aging."
Prolonged longevity in naked mole-rats: age-related changes in metabolism, body composition and gastrointestinal function.
"Maximum lifespan of these 40 g rodents (>27 year) is 9 times greater than predicted allometrically. [...]The observed absence of age-related bone loss in naked mole-rats may be explained by their employment of vitamin D-independent mineral metabolism"
Effect of oral cholecalciferol supplementation at physiological and supraphysiological doses in naturally vitamin D3-deficient subterranean damara mole rats.
"It appears, therefore, that these animals function optimally at the low concentrations of D3 metabolites found naturally. Supplementation at both physiological and supraphysiological doses of D3 may disadvantage the damara mole rat. "
Slow Aging: Insights from an Exceptionally Long-Lived Rodent, the Naked Mole-Rat
"... live in captivity an order of magnitude longer than similar-sized mice (>30 years). The common cause of death is still unknown and to date cancer has not been observed in these long-living rodents".
Natural selection is not always able to optimize, even when the necessary variation is present (as suggested where some individuals have high limits on D synthesis). In this case, large population size and the fact that phenotypic effects occur after reproductive age would reduce the efficacy of selection. If the gene(s) involved are linked to other genes with stronger selective effects, that would change the course as well. There are lots of factors that affect selection - the presence of variation is necessary but not (necessarily) sufficient.
Stephan,
Thanks for your blog, I've been reading quite a few articles trying to understand the relationship between Vitamin A and D.
I have been trying to find some info without much success on the effects of long-term, low-dose (10mg/day or 10mg/ every other day) of accutane (13-cis-retinoic acid) for skin diseases and the possible effects it might have on Vitamin D's effectiveness.
Does 13-cis-retinoic acid compete similarly to Retinyl palmitate or retinoic acid with vitamin D receptors?
According to the Vitamin D Council, even moderate doses of Vitamin A can block the effects of Vitamin D.
http://www.vitamindcouncil.org/newsletter/more-letters-on-autism.shtml
http://www.vitamindcouncil.org/newsletter/2008-december.shtml
Quoting: "The crux of the problem is that a form of vitamin A, retinoic acid, weakly activates the vitamin D response element on the gene and perhaps blocks
vitamin D's more robust activation. In fact, the authors of a 1993 study state 'there is a profound inhibition of vitamin D-activated...gene expression by
retinoic acid.'"
10mg/every other day of Accutane, considered a low dose, is still about 30,000IU/every other day. I have been taking Vitamin D to get my blood serum levels up, and yet am worried that even at 50-60ng/ml of 25OHD in my blood will not be effective in disease prevention and overall health due to the competing Vitamin A.
Perhaps 13-cis-retinoic acid (accutane) works differently and therefore doesn't compete?
However, I cannot fully understand The Vitamin D council's strong suggestion to avoid all retinoids and just to eat enough food high in beta-carotene, and Weston Price Foundation's suggestion of taking Cod Liver Oil as a health supplement.
The reason I am so intrested in this topic is because I am very concerned after reading that oral retinoids can effect telomere length (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC34517/) and seems to influence cell division hence being used in cancer treatments:
"Retinoic acid (active form of Accutane/Roaccutane) induces differentiation and reduces proliferation of stem and progenitor cells. It works on acne by inducing similar events in basel sebocytes. These same actions also lead to 13-cis-retinoic's side effects, and these are directed towards proliferating cells in the adult such as in the skin, gut and bone." Crandall 2004
"A wide ranging effect of retinoic acid is to inhibit proliferation in dividing cells, and this accounts for its frequent consideration as an anti-cancer agent."Crandall 2004.
(http://www.accutaneaction.com/Studies/2004_Crandall%20et%20al.pdf)
Oral Retinoids seem to therefore lead to more rapid aging? This seems to explain why higher Vitamin D blood serum levels correlate with slower aging?
Sorry for a long first post, but I am taking enough Vitamin D, fish-oil, probiotics, and eating and exercising according to the Primal Blueprint, yet am still very worried about taking Vitamin A (particularly low dose Isotretinoin) after reading Dr. Cannell's Newsletter on Vitamin A Toxicity.
Any Insights?
Eric
Black people should not supplement vitamin D, it has been shown to cause calcification of the arteries. I guess because of the way their skin synthesis the vitamin, supplementing does not have same effect as in white people.
http://www.sciencedaily.com/releases/2010/03/100315091259.htm
Anna,
To answer your question, go to this website - http://www.vitamindcouncil.org/newsletter/vitamin-d-race-and-cardiovascular-disease.shtml.
I think that study is flawed.
I agree. Reductionism isn't going to get us very far when health is so complicated.
Kamagra
Hi, i just received my lab results and it states that my (25OH Vitamin D3 test) D3 are 17NG/ML..low. I was RX Synthetic Vit D2 form, 50000 per week, which i do not want to take. I have been researching Vit D3 sources, i am confused, some say a powder form is better, becasue some D3 products can go rancid ( made with oils), than i have researched Carlson, Nordin Naturals, Bio-tech..so many out there, i was just recently told about Green Pastures ( correct name??)..i have also been showing signs of rheumatoid arthritis ( 3rd generation), my mom also has ostheoporoses..i would appreacaite your recomendations..i have a dairy, soy, walnut, shrimp and avocado allergies. THANK YOU!!!!
Eva, SoCal.
..just to add to my post..i have asthma as well and other allergies....also, would Vit D3 be better in cod liver oil or a capsule? i really need to get my Vit D3 up as well as Vit K i pressume? Thank you.
Eva, SoCal.
I found this post while trying to figure out whether to supplement with butter oil and/or cod liver oil for general health purposes but I was intrigued by the skin texture comment. A couple of years ago my vitamin D level was 9 and I was put on 50,000 IU for a couple of weeks. I've been supplementing with 2,000 to 4,000 IU of D3 from Carlson's since then and last time I had my vitamin D measured it was in the 30s.
A few months after I was found to be deficient, I started to get an unprecedented amount of acne. Fast-forward a year or so and I found that adding 30 mg of Zinc got rid of it. I also eliminated nuts, which seemed to cause some of the acne but not all. The difference in my skin is startling and I was wondering if you had any ideas why I had this episode in the first place and why a simple supplement like that could make all the difference.
I have gone from being eligible for Accutane to a very mild case of acne, if any. I have also recently diminished the amount of "whole grains" I eat and moved towards more of a paleo diet in the hopes that this will help me get the most out of the food I eat.
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