Microsoft word - vitamin d interview with michael holick autumn 201

“Vitamin D is like a Religious Revival; either you're a believer or Adam Thornton discusses vitamin D with Dr Michael Holick There is no doubt that the current ‘vitamin du jour’ in both the scientific literature and the lay media is vitamin D. Vitamin D is rightly in the spotlight because of the enormous amount of scientific research that has been conducted in recent years that sheds light on its ubiquitous functions in the body. This fascinating nutrient is involved in so many biochemical processes in the body it can be mind-boggling to fathom how humans have evolved to be so dependent on it. Traditionally, we would associate vitamin D with bone health, but that is just one piece of the jigsaw. We now have strong evidence that its deficiency is associated with a significant number of diseases, such as cancers of the prostate, breast, bladder, skin (that’s right!), as well as falls and fractures in the elderly, osteoporosis, multiple sclerosis, and of course rickets. But there is also good scientific evidence that vitamin D deficiency is associated with birth problems, chronic fatigue, depression, diabetes, heart disease, inflammatory bowel disease, colds and influenza, kidney disease, obesity, seasonal affective disorder (SAD).the list goes on. We used to think that the increase in colds in the winter months was because of people passing on their viruses as they stay close to each other, cooped up indoors, away from the cold weather. But now, some scientists are suspecting it is more to do with the drop in our levels of protective vitamin D, which are built up over the summer, and its effects on immune function. But why are the effects of vitamin D so far reaching? Although we often think of vitamins as substances we obtain from the diet, vitamin D is something of a special case. Yes, it is found in the diet, but it is almost impossible to obtain sufficient vitamin D from dietary sources. There is simply not enough. Vitamin D is in fact a natural steroid hormone that is synthesised in the skin from cholesterol, by the action of the sun’s UVB radiation. We get most of our requirements from the sun and, because we have evolved in direct sunshine, it is for this reason that we are so dependent on it for our health. In Spring this year, the UK’s Vitamin D Association organised the Vitamin D Experts’ Forum, a meeting of some of the world’s foremost experts on vitamin D. It boasted an impressive line-up, all of whom gave very interesting, at times impassioned talks on vitamin D. Perhaps one of the most entertaining presentations was from Dr Michael Holick. In 2007, Dr Holick received the Linus Pauling Functional Medicine Award, presented to scientists or clinicians who are influential in bringing about a paradigm shift in our thinking about a biomedical problem. At the Forum, ION was fortunate to be able to discuss his specialist subject with Dr Michael Holick. Copyright 2011 Institute for Optimum Nutrition ION: Dr Jeffrey Bland interviewed Dr Bruce Ames for his monthly audio-magazine Functional Medicine Update. Dr Ames (one of the most cited researchers in biological science) commented that his main interest is preventive medicine and nutrition and that he goes to many ‘alternative medicine’ meetings. All his physician friends tell him he’s out of his mind to go to these meetings, and he tells them, "Look, they're interested in the important things." Have you experienced this with your orthodox medical colleagues? MH: Absolutely! Although, I was in Toronto recently, at a keynote address for internal medicine physicians. There must have been more than 1,000 people in the audience. And when I introduced myself I said “vitamin D is like a religious revival; either you’re a believer, or you’re a non-believer”. And I asked the audience: “how many of you in the audience are believers?” More than 90% raised their hands. I was very surprised. But the laboratory test for 25-hydroxy-vitamin D (the main form found in the blood) is now the most ordered test by physicians in the United States. Over $100 million a year is spent on that. ION: Do you think there is a problem in the fact that we call vitamin D a vitamin? Typically vitamins are thought to have a dietary source but most of our vitamin D comes from direct sun exposure on our skin. MH: But what’s even worse is if you call it a hormone, which it is of course. Hormones have very bad connotations. So it’s a Catch 22 situation. For the informed I call it a hormone, and for others, it’s probably better to call it a vitamin! ION: There is research to suggest that vitamin D is beneficial for psoriasis, but if an individual is obese, how is the efficacy of the treatment affected, considering that fat cells sequester vitamin D? MH: It turns out that it’s only activated vitamin D that helps psoriasis, so it’s a pharmaceutical, and it has to be topically applied. Taking vitamin D orally has no benefits for psoriasis. So if the individual is obese it doesn’t matter, because of the topical application. In addition, if the individual were to lose weight and to release the vitamin D, there would be no toxic overload of vitamin D because as the fat is broken down so is the vitamin D. So you don’t raise the blood level. But the other side of the coin is - and we’re doing the research now - that vitamin D induces maturation of the fat cell, and may play a very important role in how fat cells utilise fat. So vitamin D deficiency is associated with obesity, but it may also be that the vitamin D deficiency makes the obesity worse. ION: Apparently, according to research, only a quarter of endogenous or ingested vitamin-D is hydrolysed and converted to its active calcitriol form by kidneys or locally by tissues. Is there any research happening on how this can be improved and Copyright 2011 Institute for Optimum Nutrition has this mechanism always been so inefficient or is it just a characteristic of the modern western man? MH: Probably none of the above is true. Because 1,25-D circulates at 1000+ concentration it has nothing to do with efficiency. It’s just the opposite; that your body cares about your blood calcium more than anything else. And it will do anything to preserve your serum calcium because for all neuromuscular and metabolic functions, it’s key. So Mother Nature cleverly decided that if vitamin D was playing such a key role that even if you had almost undetectable levels of 25-hydroxyvitamin D you would still be able to make more than enough 1,25-dihydroxyvitamin D – calcitriol. Calcitriol levels are far more elevated when you’re vitamin D deficient, so it has nothing to do with the efficiency of conversion. And parathyroid hormone, phosphorus, and calcium all play a role in regulating levels. ION: Dr John Cannell (from the Vitamin D Council) wrote on their website about the influence of high vitamin A on vitamin D requirement and function, and that vitamin A can weakly block some of the nuclear receptors for vitamin D. MH: In my opinion, none of that’s correct. And the data that Dr Cannell is really referring to was a) speculation, and b) in cultured skin cells. In these cultured human skin cells, they put in a lot of vitamin A to try to steal away RXR [retinoid X receptor – a nuclear receptor that is activated by retinoic acid, a metabolite of retinol (vitamin A)]. And as a result, they decrease the anti-proliferative activity of 1-25 D. But these are very high concentrationsMost dietary vitamin A comes from beta carotene, which is inefficiently converted in the body, so retinoic acid levels would not be high enough to have this effect. And furthermore, there was a really neat paper that was presented in Madrid when I was there for a meeting a couple of weeks ago. They now believe that cis-retinoic acid binds RXR with the Vitamin D Receptor complex and they may play a synergistic role, not an antagonistic one. ION: Although supplementing vitamin D is proven safe even in high doses, do you feel there are potential problems with health professionals not understanding the mechanisms of vitamin D? For example, we know that various nutrients tend to function in synergy with each other. Do you find that’s also the case with vitamin D? MH: Most of the vitamin D actions are independent of other nutrients. Mother Nature has vitamin D’s metabolism so tightly controlled in the kidney, it’s never really an issue. ION: W ith the increasing interest in personalised medicine, and yet the expense of private lab testing, how do we determine an individual’s vitamin D requirement? MH: I’m glad you asked that! I’ve treated thousands and thousands of patients, most of whom either have disease, malabsorption problems orallergies, and low vitamin D levels. And I have never found it makes any difference as to what your starting Copyright 2011 Institute for Optimum Nutrition [blood vitamin D] level is. You will still get up to the same level whatever the total dose of vitamin D you give. So you take 100ius, blood levels go up a little bit and stay there. If you give 500ius it goes up a little bit more and if you give 1000ius it goes up a bit more still. But it’s curious as it doesn’t tend to rise as you might have thought even if you take a lot. It goes up to the right physiological level, and it stays there. In our Archives of Internal Medicine paper in 2009 1– over six years we used the equivalent of 3,000iu a day. It went up and stayed there! So it’s very safe. ION: Do you feel that regarding the [American] Institute of Medicine’s new upper limit for vitamin D they seem to be regarding it as a novel nutrient or drug rather than an essential molecule which we have evolved to use in many of our physiological processes? MH: The Institute of Medicine have doubled the upper limit, which I think is great! But they probably could have doubled it again. ION: There is often a suspicion of political or commercial motives when there is a conflict between government-recommended upper limits and what many scientists and practitioners think should be a higher limit. MH: I think that they were very concerned about this being a population based recommendation as opposed to thinking that their recommendation was going to benefit the health of everyone from all aspects. They just didn’t want to go there. ION: So there’s nothing underhand here. MH: In my opinion no. Contrary to what a lot of people have said (and even I am critical of the IOM), from my perspective the good news is how far they raised the RDA. That’s amazing! There’s no other nutrient with which they’ve ever done that before. And so I think they went in the right direction, but just didn’t go far enough. But what is going to help is that, as a result, more foods will be fortified with vitamin D, with higher amounts, and definitely more supplements will be out there with higher ION: Do you anticipate any issue with taking vitamin D supplements in the winter? If you consider that in the autumn we tend to lay down more fat do we then have more potential to store vitamin D (because it’s stored in fat tissue)? MH: No, you instantly store vitamin D no matter what. Even anorexics who have a tiny amount of fat will still store vitamin D. And evolutionarily it’s pretty clear that you make vitamin D in the spring, summer and autumn, and then you release it in the winter time as you use your body fat. ION: A few observational studies are now showing increased risk of cancer at high as well as low vitamin D3 serum levels. Are you aware of what might be causing this Copyright 2011 Institute for Optimum Nutrition or whether the observations are correct? MH: If you take a huge amount it can cause calcinosis, and kidney stones, and calcified blood vessels. There is a lawyer who accidentally took millions of ius, and when I subsequently treated him I found he had blood levels of over 1,000ng per ml. And all I did was tell him to get no more sun without sunscreen, no vitamin D. His blood levels came down to about 5nm per litre; he was perfectly fine. So even the toxicity in this case was benign. The more important issue with toxicity is that physicians feel obligated to treat, and the way you treat vitamin D toxicity is with glucocorticoids (steroid hormones that bind to the glucocorticoid receptor), and there you really get into trouble. ION: What are your views on vitamin D reducing seizures in epilepsy? Studies have shown it helps some, but can increase seizures in others. MH: Seizure medication increases the risk of vitamin D deficiency. I am aware that in animals vitamin D can alter seizure threshold, reducing risk. I’m not aware of any human data suggesting it increases risk. ION: Recently there has been some research on the effects of vitamin D on both male and female infertility, such as sperm motility, PCOS, and endometriosis. Have you come across any case where vitamin D was successfully used? MH: I‘m aware of it, and I’m aware of the animal studies. They look intriguing. ION: When you consider all of the many aspects of health vitamin D is associated with, do you think there is a concern that some may think it is the answer to everything? How do we temper that? MH: Simple, at least from my perspective. Even if a chronic disease turns out to be associated with vitamin D deficiency, there really is no downside to increasing vitamin D. And I think that our hunter-gatherer forefathers and Africans out in the bush, their blood levels are probably in the range of 150 nanomoles per litre, and that’s probably where we all should be. ION: Can you say anything bad against vitamin D? MH: W ell the only thing is if you have granulomatous disorder (hereditary disease in which the immune system is unable to make superoxide radicals to kill pathogens and walls them off in masses of tissue called granulomas). What doctors normally do for them is to make them vitamin D deficient. And that’s a big mistake. So I always keep them between 50-75 nm/l and they usually do very well. ION: Dermatologists and other health professionals are very concerned about the skin cancer issue. We know that most cancers occur in sites on the skin that are away from those that are exposed to sunlight. Could it be argued that the cancer Copyright 2011 Institute for Optimum Nutrition cells develop in areas exposed to sunlight but then travel to parts of the body that are not protected by localised increased concentrations of vitamin D? MH: There’s a simple explanation. Every one of your melanocytes (melanin- producing skin cells) has the ability to become malignant. And the immune- surveillance of the body will usually take care of any melanocyte that becomes malignant. If you get sunburn, my sense is that you damage your immune surveillance at the same time that you damage your melanocyte. So your immune surveillance no longer sees a potentially malignant melanocyte. And, since you have melanocytes distributed over your entire body, every one of those melanocytes has the ability to become malignant and as a result most malignancies occur on the least sun-exposed areas because very few areas are sun exposed. And do you know why melanoma is so malignant? Have you heard of the Slug gene? Embryonically, melanocytes all develop from the neural crest cells in the brain and they all migrate throughout the entire body and are distributed evenly throughout your skin in utero. And it’s the Slug gene that’s responsible for that. This gene gets its name from studies done on fruit flies and when they mutated the gene the flies then looked like slugs. And the Slug gene is responsible for causing you to be able to have that cell make all kinds of collagenases and other proteins move through the cellular cytoplasm and through the tissues to get to where it’s going as the foetus develops in the womb. As soon as these proteins get to their site the Slug gene is permanently turned off. But in cancer, as soon as the cell becomes malignant, guess what gets turned back on? So now it becomes like ET – it wants to go home – so instantly it thinks it wants to become embryologic again, so it dives right back into the circulation and goes back into the brain. MH: I’m happy to educate! What I really like is to turn lights on in people’s heads and they say “oh my God, that actually makes sense!”, as opposed to tell you that 15 genes are up-regulated or down-regulated. ION: Do you sometimes think you hit the jackpot with choosing vitamin D as your speciality? MH: W ho’d have guessed?! And it was all serendipitous because I had no interest in working with vitamin D. People ask why I do so much travelling and giving talks: if the fish are biting, you go fishing! ION: From your experience, do you think it’s more important to try and educate the health professionals or the layperson? MH: The layperson! That’s what’s happening in the United States: it’s the lay press, and the public going to the doctors, and educating the doctors. I was a keynote speaker at a family medicine group and this woman came up to me and wanted to Copyright 2011 Institute for Optimum Nutrition shake my hand and congratulate me, but I hadn’t a clue who she was. It turned out she was a doctor and the former President of the Family Healthcare department for Massachusetts. I didn’t know why she was so enthusiastic, and she said “you saved my life!. about two years ago [when your scientific vitamin D review was published] a patient came to me with your review and told me that “I have all these aches and pains in my bones and muscles, just as it’s described here in this review. I think I’m vitamin D deficient.” Her response initially was “I don’t really think so but we’ll measure it”. They found that the patient was vitamin D deficient. Then the doctor realised that she’s about 45 years old, super busy and never gets out into the sun, and is also having aches and pains in her bones and muscles but assumed it was her stress levels and everything else, until she realised “oh my God, I’m probably vitamin D deficient as well!” She took vitamin D and said “I feel 20 years younger!” ION: So perhaps the conclusion could be that when someone’s lifestyle indicates they don’t get regular direct sunlight exposure, checking vitamin D should be the first port of call for many different conditions? MH: Absolutely! And for those who are deficient and have osteomalacia (the adult form of rickets), it has dramatic effects. It’s incredible. ION: Do you think there’s any correlation between that and Chronic Fatigue Syndrome? MH: Yes, for sure. I think a lot of that is due to D deficiency. Chronic Fatigue Syndrome, chronic pain syndrome, fibromyalgia. ION: It’s interesting now, that with the Functional Medicine model that is slowly being adopted on both sides of the Atlantic. Taking a systems biology approach, and appreciating environmental influences on health and disease, it does make you wonder where the pharmaceutical model is going to go, in the years to come. MH: Some of these drugs are so expensive. There was one that is good for melanoma which costs $20,000-$30,000 a year, and they showed that you live an additional six months. ION: Whether we call vitamin D a vitamin or a secosteroid hormone, is there much resistance from any groups of health professionals that you’ve come across, maybe the dermatology sector? MH: For sure the dermatology, yes! Obstetricians too. There are studies in rodents that if you give them really high dose vitamin D it can damage their hearts. And so obstetricians are paranoid about vitamin D because they’re worried it will cause birth defects in humans. And then the third group that still doesn’t completely get it are nephrologists. Because they think that if the kidneys can’t activate vitamin D, then you can give activated vitamin D compounds and don’t need vitamin D to maintain Copyright 2011 Institute for Optimum Nutrition 25-hydroxyvitamin D blood levels - but you definitely do. ION: What do you think of trialling mega-doses of vitamin D under certain conditions? MH: I don’t know what you mean by mega-doses, but I’m giving 50,000 units, once a week for eight weeks. That’s 7,000 units a day. That would be considered a mega- dose but I consider that filling up the tank. ION: Eight weeks? But I read that it take up to a year to replete someone’s stores of vitamin D? MH: Absolutely untrue! Our paper in the Archives of Internal Medicine proved a point. All the people were deficient, and two months later they were all sufficient. There are a lot of people out there who are very pseudo-knowledgeable who seem to like to give their opinion. ION: Do you have a plan for where you would like the research to go? MH: Well, we’re right now heavily involved in obesity research. And the other area is related to the question everyone is asking: ‘is sunlight the same as a supplement?’, and it probably is not. Because you do make a whole host of different photo-products yet no-one has asked the question in science ‘what are they doing? Why would your body make them if they weren’t having any effects?’ So I’m confident that over time we will find some additional benefits from exposure to sunlight above and beyond what you can get from taking a supplement. ION: Could you compare the photosynthesis taking place in plants for energy to the photosynthesis in animals of vitamin D? Both are absolutely crucial and have so many contributory effects to the growth and health of the organism. MH: Yeah, sure! Not only that, but we showed that organisms that existed in the Atlantic ocean for over 500 million years were making vitamin D. And that over 1% of the dry weight of phytoplankton is pro-vitamin D. So there is a major fundamental reason why pro-vitamin D and vitamin D exist in the earliest life on Earth. It is probably as crucial as photosynthesis, even for phytoplankton. Copyright 2011 Institute for Optimum Nutrition Afterword
The scientific literature and lay press have focussed on a number of macro- and micronutrients and biotics over the years. Of many to choose from we’ve had omega 3s, probiotics and now vitamin D. So what will be next? If Professor Bruce Ames has any say in the matter, vitamin K will be the next big thing. ION will be reporting on what’s going on with vitamin K soon. Dr Holick’s book The Vitamin D Solution is published by Plume and is available from Amazon and all good bookshops. A recommended read. 1Pietras, S.M. et al. (2009) Vitamin D2 Treatment for Vitamin D Deficiency
and Insufficiency for Up to 6 Years. Archives of Internal Medicine, 169 1806-1808.
Copyright 2011 Institute for Optimum Nutrition


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