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Due to some technical difficulties, a poorly formatted version of the recent newsletter on vitamin D supplements was sent out to subscribers. We apologise for the inconvenience. Here is the newsletter as it was supposed to look. We hope it helps.
It seems a sensible time of year in the Southern Hemisphere at least to remind people of the benefits of vitamin D supplementation. This is the time when people who have not been careful about their vitamin D status are at risk of relapse.
Vitamin D Supplementation
It seems clear that we in the medical profession have been overly concerned with the potential for toxicity from supplementing with vitamin D, and that we have under-estimated the doses required for optimal health quite significantly. Vitamin D levels in the body can be easily measured with a simple blood test. A level of less than 25nmol/L is considered currently to represent moderate to severe deficiency, a level of 25-50nmol/L mild deficiency, and a level of 50-75nmol/L borderline deficiency.
There is quite a bit of evidence that we have set these levels too low and that optimal levels are really quite a bit higher.(1) Even at these levels, it has been shown that 80% of women and 70% of men living in hostels in Victoria, New South Wales and Western Australia are deficient.(2) In women in Geelong, 30% had deficiency in summer, and 43% in winter, and the rate of falls and fractures was higher in winter.(3, 4)
Key point: People with MS should check their level of vitamin D annually and keep it around 150nmol/L or higher
The recommended daily allowance of vitamin D in Australia is 200IU. This amount of vitamin D is way too low. It is based on the amount required to prevent rickets. It is equivalent to the amount of vitamin D your skin would make in 6 seconds of all over sun in Perth on a summer’s day. Vieth and others have shown that in sunny countries where these diseases are uncommon, the vitamin D levels are at least 100-140nmol/L, and more like 135-225nmol/L, and that a level of 200nmol/L may actually be optimal.(5) Others have suggested a level as high as 250nmol/L may be optimal.(6)
Australian laboratories have changed their recommended ‘normal’ vitamin D levels considerably in recent years. Previously, above 50nmol/L was suggested as normal. Then more recently the range of 50-150nmol/L was being defined as the therapeutic range for optimal bone health, although it is likely that optimal immune function is achieved at levels higher than those required for bone health. And very recently, the normal range is being quoted as 75-250nmol/L as more information about the beneficial effects of ‘high normal’ levels comes in.
People with MS should aim to be above the middle of that range. To achieve a level of 100nmol/L requires daily intake of about 4 000IU of vitamin D for people who are not getting any sun. To get to 140nmol/L needs about 10 000IU a day in the absence of sunlight. It has been shown that average healthy men’s bodies use about 3 000 to 5 000IU a day.(7)
It is not possible to get toxicity from vitamin D if it all comes from the sun. Only supplements can potentially produce toxic levels. The only published toxicity however is from supplements of 40 000IU a day.(8) Indeed, Vieth and colleagues reported via the internet a groundbreaking dose escalation study of vitamin D3 in people with MS.(9) More recently this has been published in a major journal.(10) They gave increasing doses of the hormone to 12 people over 28 weeks, increasing the dose from 4 000IU per day up to 40 000IU per day. Measured levels of vitamin D in the blood of these people were extraordinarily high, much higher than what we have previously regarded as toxic, with average levels increasing to around 400nmol/L and the highest measured level 800nmol/L.
Despite these apparently ‘toxic’ levels, no patient developed high calcium levels or any side effects. Although this study aimed to look at the safety of high dose vitamin D supplements, and was not primarily designed to detect outcomes in the medical condition of these people with MS, it is interesting to note that the mean number of new MS lesions more than halved over the short period of the study from 1.75 to 0.83 (p=0.03). And in data presented to the American Academy of Neurology meeting in 2009, the researchers showed that people with MS who took the larger doses (averaging 15 000IU per day) in the study had two-thirds fewer relapses than those taking ‘standard’ doses through their GPs of 1 000IU a day. It is clear now that supplementation with vitamin D at quite high doses is very safe, and the way is now clear to use these larger doses in research situations to examine the effect on relapse rates and disease progression.
The right form of vitamin D to take is vitamin D3 or cholecalciferol. This is the natural form that is made in the body in response to sunlight. In Australia, because it is such a sunny country, regulators have not in the past allowed vitamin D to be sold at any reasonable dosage level. Health food shops have been able to sell D3 at 1 000IU doses. Until recently, the only form available from doctors in Australia was vitamin D2 or ergocalciferol. This is synthetic, available on prescription only, and is not the optimal form to take. It is also expensive. Vitamin D3 on the other hand is cheap, and because it is naturally occurring cannot be patented by drug companies. The easiest way to obtain supplies at a reasonable strength is over the internet. A 5 000IU capsule is available quite cheaply at www.vitamin-D-max.com
, a US company, or www.seeknatural.co.uk/product-1798.html
, a UK company, and a 2 400IU capsule from www.iherb.com
. Both are fine for children as the capsules can be broken apart and the powder sprinkled on food like morning cereal, and the softgel capsule in olive oil can be squeezed onto food or into drinks.
My recommendation is that when first diagnosed, people should ask for a vitamin D level immediately. It is very common for this first level to be low, and often this is why the attack happened. Australian researchers are now calling for ‘Active detection of vitamin D insufficiency among people with MS and intervention to restore vitamin D status to adequate levels … as part of the clinical management of MS’.(11) Many neurologists I know are now doing this routinely at diagnosis. If the level is very low, it can be brought up very quickly with a one-off megadose of vitamin D followed by regular capsules.(12)
For people with initial levels indicating severe deficiency (less than 12.5nmol/L), a one-off megadose of 600 000IU raised levels to an average of 73nmol/L.(12) This is still probably half the level which may be optimal in MS, but it can be seen that even large doses of this vitamin are quite safe. My suggestion is to get a one-off dose like this if the initial level is low, and then take a regular supplement of around 5 000IU a day in winter, or more if required, to get the level to around 150nmol/L. The level should be checked at the end of each winter of supplementation to make sure it is not being overdone. It may in fact be more important for men to keep their vitamin D levels high and check their levels frequently as it has been shown that women with MS have considerably higher levels than men with MS.(13) Holick, a world authority on vitamin D suggests annually checking one’s vitamin D level as a routine.(14)
Key point: A very low vitamin D level can be raised quickly and safely with a one-off megadose of vitamin D
Supplementing with vitamin D of up to 10 000IU per day is now thought to be very safe, although in the past many medical authorities have been concerned about the possibility of side effects with doses of this magnitude. Hathcock et al have applied the risk assessment methodology used by the Food and Nutrition Board in the USA to derive a revised safe Tolerable Upper Intake Level (UL) for vitamin D3.(15) Their risk assessment based on relevant, well-designed human clinical trials of vitamin D3 concluded that the UL is 10 000IU vitamin D3 per day, that is, it is safe to take up to 10 000IU of vitamin D3 per day. Even with plenty of sun exposure, supplementing even up to this dose appears to be quite safe.
To illustrate the safety limits of supplementation, Kimball and Vieth reported in 2008 the cases of two men who had been supplementing with vitamin D.(16) One had been taking 8 000IU per day for three years. This resulted in a blood level of 260nmol/L, and no changes in any measured parameters of calcium. The second, a 39 year old man with MS, had been steadily increasing his self-prescribed dose of vitamin D over four years, from 8 000IU per day to a whopping 88 000IU per day. This latter level would be expected to produce some toxic effects. In fact, the amount of calcium in his urine started to rise, and then blood calcium levels started to go up, with a vitamin D level in his blood of 1126nmol/L. He displayed no symptoms though. At that point he stopped taking vitamin D, and within two months, all his blood tests were normal, although vitamin D levels remained high at 656nmol/L. While not recommended, this at least shows that it takes very large doses of vitamin D to produce any increase in calcium levels and toxicity.
Vitamin D and Bone Health
It is interesting to note that most Western societies have overdone their public health messages about sun avoidance so much that a very large proportion of their populations are low in vitamin D or frankly deficient. As the main effect of vitamin D in the body is to extract calcium from food we eat and incorporate it into bone, this has resulted in a virtual epidemic of osteoporosis in Western countries. Rather than modify the messages to promote modest sun exposure, which we have seen has a range of health benefits, the response has been to recommend calcium supplementation and to develop ‘bone-hardening’ drugs like Fosamax. As a result, we have a huge food industry growing up around adding calcium to foods and encouraging substantial dairy consumption.
The evidence however is that this is not making an impact on osteoporosis and bone fractures. In fact, there is evidence that populations that eat mainly vegetarian or vegan diets have lower rates of osteoporosis and fractures. A study from Harvard in the late 1990s for instance showed that the incidence of forearm and hip fractures in men was no lower in those with high calcium intakes than those with low intakes.(17) Likewise a very large prospective study from Boston of over 77 000 women showed that there was no difference in fracture rates in women with high calcium intakes compared with those with low intakes.(18) Indeed there was a trend to higher fracture rates in those with high calcium intakes. A detailed review of the literature shows that there is no evidence that increasing cow’s milk consumption has any beneficial effect on children’s bone health.(19) The Centre for Nutrition and Food Safety at the University of Surrey recommended that a 'fruit and vegetable' approach to osteoporosis may provide a very sensible alternative therapy for osteoporosis, and is likely to have many other health benefits.(20)
McCarty suggests that vegan diets in combination with vitamin D supplementation represent the best alternative to getting adequate sun exposure, in terms of achieving the wide-ranging health protection conferred by optimal sun exposure.(21) This seems to be related to the amount of phosphate in the diet; phosphate is low in vegan diets, whereas calcium supplements tend to raise the phosphate.
The problem with widespread calcium supplementation for populations of people with low vitamin D levels is that most of the calcium that is added to food is not absorbed into the body because of the low vitamin D. It has been shown that people with a blood level of vitamin D of 86.5nmol/l for example, absorb two thirds more calcium than those with blood levels of 50nmol/L, yet both levels are currently considered reasonable.(22) For people with osteoporosis, the best thing to do is get out in the sun regularly as per the guidelines on this website, not eat more calcium. And of course, it’s easier to exercise more when outside, further strengthening bones. MS and osteoporosis often go hand in hand, especially for people with advanced disease, because they don’t exercise much, and don’t get outside much. People with MS must get out in the sun.
The Risks Associated with Calcium Supplementation
As we have discussed, the main job of vitamin D in the body is to absorb calcium from the diet and lay it down in bone, thus forming normally strong, healthy bones. Unfortunately, given the evidence that we are in the midst of an epidemic of vitamin D deficiency and that vitamin D levels are falling in the community, and hence not enough calcium is being absorbed, osteoporosis has become widespread, resulting in a large number of fractures of long bones and the hip, particularly in our elderly.
Instead of treating the cause of this problem, that is getting people out in the sun more often, or failing that, supplementing with adequate doses of vitamin D, a whole industry of calcium supplementation has appeared. As consumers, we now face constant advertisements about whether we are getting enough calcium, designed to get us to take calcium supplements. The dairy industry has seen an opening here to market its products as high in calcium and therefore healthy, obscuring the very real health risks associated with dairy products, particularly for people with multiple sclerosis.
It has actually taken a long time for researchers to begin to investigate whether this widespread calcium supplementation is doing any good, or more particularly, whether it is possibly doing harm. After all, many of our elderly are on drugs called calcium channel blockers, particularly those with heart and vascular disease, and intuitively it seems problematic to be giving them the very mineral whose effects we are trying to block in the body.
Recently, a number of well designed trials and meta-analyses have raised serious doubts about the safety of calcium supplementation. A major randomised controlled trial from the University of Auckland, published in 2008 in the British Medical Journal, examined 1471 postmenopausal women.(23) Of these, 732 were randomised to calcium supplementation and 739 to placebo. Heart attacks were more common in the calcium group than in the placebo group (45 versus 19, p=0.01). The investigators also looked at the combined end point of heart attack, stroke, or sudden death, and found that this was also more common in the calcium group (101 versus 54, p=0.008). It should probably come as no surprise that calcium supplementation in these elderly women was associated with increases in serious cardiovascular event rates.
This increased risk might even be considered acceptable by some if the benefits of calcium supplementation were very marked. But there are serious doubts about whether there is really any benefit in terms of bone health from supplementing with calcium. Interestingly, researchers from the same institution showed that calcium supplementation actually increased hip fracture risk by 50%.(24) A 2007 meta-analysis from the Harvard School of Public Health Pooled reported that randomized controlled trials showed no reduction in hip fracture risk with calcium supplementation, and that an increased risk was possible.(25) For other fractures, there was a neutral effect.
It really is time for a re-appraisal of the whole calcium-vitamin D issue in health. Clearly, vitamin D is very important for a variety of reasons, not least its helpful effects on mood, muscle strength, cancer, vascular and autoimmune disease. A real problem is that when we do supplement with vitamin D, we generally use too low a dose. We need to raise the level to a minimum of 75nmol/L to get any benefit at all for bone health(26), and it probably needs to be twice that to really get the full health benefits for other conditions. We know for example that a level of 100nmol/L or so is the threshold level above which there is a great protective effect against developing MS.(27)
As for calcium, like many other heavily-marketed supplements, now that the evidence is coming in, we can see that it pays to be very, very selective about what supplements to take. Supplements need to be taken for a good reason, with a therapeutic aim in mind, and utilising the best available evidence to support their use. For people with adequate vitamin D levels (and for people in most geographic regions this means supplementation with relatively large doses of vitamin D in winter), calcium supplementation is completely unnecessary. For those who avoid the sun or cannot get much sun in winter, and those with osteoporosis, supplementation with at least 5 000IU of vitamin D daily is recommended, rather than with calcium. Calcium supplementation, on the basis of current evidence, poses too great a risk to human health, and is not recommended.
People with MS can feel comfortable that sunlight and/or vitamin D are likely to improve their outcome from the disease, and protect them from many others in addition. In winter, in most places in the world, a vitamin D supplement is necessary to keep vitamin D levels optimal at around 150nmol/L or higher. In some places in the world, and for those who avoid the sun, year round supplementation is necessary.
1. Vieth R. Why the optimal requirement for Vitamin D(3) is probably much higher than what is officially recommended for adults. J Steroid Biochem Mol Biol 2004;89-90:575-9.
2. Flicker L, Mead K, MacInnis RJ, et al. Serum vitamin D and falls in older women in residential care in Australia. J Am Geriatr Soc 2003;51(11):1533-8.
3. Pasco JA, Henry MJ, Nicholson GC, Sanders KM, Kotowicz MA. Vitamin D status of women in the Geelong Osteoporosis Study: association with diet and casual exposure to sunlight. Med J Aust 2001;175(8):401-5.
4. Pasco JA, Henry MJ, Kotowicz MA, et al. Seasonal periodicity of serum vitamin D and parathyroid hormone, bone resorption, and fractures: the Geelong Osteoporosis Study. J Bone Miner Res 2004;19(5):752-8.
5. Grant WB, Holick MF. Benefits and requirements of vitamin D for optimal health: a review. Altern Med Rev 2005;10(2):94-111.
6. Moan J, Porojnicu AC. [The photobiology of vitamin D, a topic of renewed focus.]. Tidsskr Nor Laegeforen 2006;126(8):1048-52.
7. Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr 2003;77(1):204-10.
8. Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr 1999;69(5):842-56.
9. A phase I dose escalation study of vitamin D3 with calcium supplementation in patients with multiple sclerosis. Multiple Sclerosis Resource Centre, 2002. (Accessed 26 February 2006, at <shortened url
10. Kimball SM, Ursell MR, O'Connor P, Vieth R. Safety of vitamin D3 in adults with multiple sclerosis. Am J Clin Nutr 2007;86(3):645-51.
11. van der Mei IA, Ponsonby AL, Dwyer T, et al. Vitamin D levels in people with multiple sclerosis and community controls in Tasmania, Australia. J Neurol 2007.
12. Diamond TH, Ho KW, Rohl PG, Meerkin M. Annual intramuscular injection of a megadose of cholecalciferol for treatment of vitamin D deficiency: efficacy and safety data. Med J Aust 2005;183(1):10-2.
13. Barnes MS, Bonham MP, Robson PJ, et al. Assessment of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D3 concentrations in male and female multiple sclerosis patients and control volunteers. Mult Scler 2007;13(5):670-2.
14. Holick MF. The vitamin D epidemic and its health consequences. J Nutr 2005;135(11):2739S-48S.
15. Hathcock JN, Shao A, Vieth R, Heaney R. Risk assessment for vitamin D. Am J Clin Nutr 2007;85(1):6-18.
16. Kimball S, Vieth R. Self-prescribed high-dose vitamin D(3): effects on biochemical parameters in two men. Ann Clin Biochem 2008;45(Pt 1):106-10.
17. Owusu W, Willett WC, Feskanich D, Ascherio A, Spiegelman D, Colditz GA. Calcium intake and the incidence of forearm and hip fractures among men. J Nutr 1997;127(9):1782-7.
18. Feskanich D, Willett WC, Stampfer MJ, Colditz GA. Milk, dietary calcium, and bone fractures in women: a 12-year prospective study. Am J Public Health 1997;87(6):992-7.
19. Lanou AJ, Berkow SE, Barnard ND. Calcium, dairy products, and bone health in children and young adults: a reevaluation of the evidence. Pediatrics 2005;115(3):736-43.
20. New SA. Nutrition Society Medal lecture. The role of the skeleton in acid-base homeostasis. Proc Nutr Soc 2002;61(2):151-64.
21. McCarty MF. A moderately low phosphate intake may provide health benefits analogous to those conferred by UV light - a further advantage of vegan diets. Med Hypotheses 2003;61(5-6):543-60.
22. Heaney RP, Dowell MS, Hale CA, Bendich A. Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. J Am Coll Nutr 2003;22(2):142-6.
23. Bolland MJ, Barber PA, Doughty RN, et al. Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. BMJ 2008;336(7638):262-6.
24. Reid IR, Bolland MJ, Grey A. Effect of calcium supplementation on hip fractures. Osteoporos Int 2008;19(8):1119-23.
25. Bischoff-Ferrari HA, Dawson-Hughes B, Baron JA, et al. Calcium intake and hip fracture risk in men and women: a meta-analysis of prospective cohort studies and randomized controlled trials. Am J Clin Nutr 2007;86(6):1780-90.
26. Bischoff-Ferrari HA, Dawson-Hughes B. Where do we stand on vitamin D? Bone 2007;41(1 Suppl 1):S13-9.
27. Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 2006;296:2832-8.
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