Negative JAMA article about vitamin D supplementation

[DianaCox]

I don't know how to critique this, but it sounds off to me. But I need to study it and figure out what is wrong. I'm copying the entire article because JAMA often allows access for a while, and then cuts it off. The references didn't copy correctly ...

Editorial | January 04, 2016
Vitamin D Supplementation and Increased Risk of Falling
A Cautionary Tale of Vitamin Supplements Retold
FREE ONLINE FIRST
Steven R. Cummings, MD1,2; Douglas P. Kiel, MD, MPH3; Dennis M. Black, PhD2
[+] Author Affiliations
JAMA Intern Med. Published online January 04, 2016. doi:10.1001/jamainternmed.2015.7568
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The randomized clinical trial (RCT) by Bischoff-Ferrari et al1 in this issue of JAMA Internal Medicine shows that vitamin D supplementation is associated with the risk of falls. Two “high” doses (60 000 IU of vitamin D3 per month or 24 000 IU vitamin D3 plus 300 mg of calcifediol per month) achieved a serum 25-hydroxyvitamin D (25[OH]D) level of 30 ng/mL in 80% of participants, a level that has been recommended as best for reducing the risk of fractures and for other health benefits (to convert 25[OH]D to nanomoles per liter, multiply by 2.496).2,3 However, compared with a dose of 24 000 IU of vitamin D3 per month (equivalent to 800 IU per day), the higher doses had no effect on lower extremity physical performance and increased the risk of falls. A previous RCT4 in women of the same age showed that 500 000 IU of vitamin D per year achieved serum 25(OH)D levels of at least 30 ng/mL in most participants but significantly increased risk of falls by 15% and fractures by 26%.

A theoretical possibility has been raised that periodic administration of high doses of vitamin D accounts for the increased risk of falls and fractures.5 That hypothesis should be tested by placebo-controlled trials showing that a daily dose of 2000 IU, for example, reaching serum 25(OH)D levels of at least 30 ng/mL reduces the risk of falls and fractures.

The trial in this issue1 had no placebo group and, therefore, could not test the effects of supplementation with 800 IU of vitamin D per day. However, a recent placebo-controlled trial by Uusi-Rasi et al6 found that an 800 IU per day supplement had no effect on physical function or risk of falls or injurious falls, whereas an exercise program reduced the risk of injurious falls by about half. Another trial found that 800 IU daily had no effect on lower extremity function or risk of falls in postmenopausal women 75 years or younger.7

It is uncertain whether any dose of vitamin D supplementation reduces the risk of falls or fractures in community-dwelling older adults. Previous meta-analyses of RCTs had differed about whether vitamin D supplements reduce the risk of falls8- 11 or fractures8,12- 14 in community-dwelling elderly individuals. In contrast meta-analyses15- 17 have shown that 800 IU of vitamin D and 1200 mg of calcium reduced the risk of hip fracture and mortality for patients dwelling in institutions. These patients should receive calcium and vitamin D supplements.

Clinicians should not recommend vitamin D supplements for other putative health benefits. There is no evidence from meta-analyses of RCTs that vitamin D supplementation reduces the risk of cardiovascular disease or cancer.13,18 In addition, a recent trial19 found that 1000 IU of vitamin D per day, with or without calcium, did not decrease the risk of colon cancer or recurrent adenomas in those with a history of colon adenomas.

The vitamin D story seems to be following the familiar pattern observed with antioxidant vitamins. Enthusiasm for the health benefits of vitamin supplements is coupled with the belief that “vitamins” are inherently safe and reinforced by observational studies showing, essentially, that healthy people have higher vitamin levels. Then RCTs and meta-analyses20 proved that the supplements in fact increase mortality (β-carotene, vitamin E), or have no health benefits (vitamin A, vitamin C).

The strategy of supplementation with vitamin D to achieve serum levels of at least 30 ng/mL has not been established by RCTs to reduce the risk of falls and fractures. It may increase the risk of falling. Until that approach is supported by randomized trials with updated meta-analyses, it would be prudent to follow recommendations21 from the Institute of Medicine (IOM) that people 70 years or older have a total daily intake of 800 IU of vitamin D without routine measurement of serum 25(OH)D levels. It is prudent to get recommended intakes of vitamin D and other vitamins from a balanced diet with foods that naturally contain what is manufactured into supplements.

ARTICLE INFORMATION | REFERENCES
Corresponding Author: Steven R. Cummings, MD, San Francisco Coordinating Center, Coordinating Center, 185 Berry Street, Lobby 5, Suite 5700, San Francisco, CA 94107 ([email protected]).

Published Online: January 4, 2016. doi:10.1001/jamainternmed.2015.7568.

Conflict of Interest Disclosures: None reported.

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21
Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academies Press; 2011.

 

[Clematis]

I read this in NYT or WSJ in the past day or two and went... HUH?

 

[Munchkin]

Questions, questions....

Size of the sample? Average age of the sample? Time period of study. I wonder if you can search out falls for the same group in the general population to make up for lack of a placebo group? It APPEARS to be coincidental and or anecdotal.

Here's a whole group of people taking high dose D forever and I don't think we are falling all the time...

Yanno data bases like Kaiser Permanente So-Cal can be great but you CAN use them to prove or disprove almost anything!

 

[Larra]

Or maybe the people with better D levels felt so good that they did more activities that led to falls, while those with low levels sat on their butts because they felt like crap.
More to the point, they are at worst saying increased falls and not saying increased fractures. If you fall and dust yourself off and get back up with just a bruise or 2, no big deal. Or maybe a level of 30 is still bad, but if you take enough D to get to the middle of the normal range instead of the lower end you do better? Who knows!
It would have been interesting, also, to measure these people's PTH levels to see if the people with lower levels were able to maintain a normal PTH or if their PTH became elevated. I do agree with their point that people jump onto different trends, like the Vitamin E business, or before that Vitamin C supposedly preventing illness, when there is no real evidence to support it, and we cling to those beliefs for years until they are definitively disproven, even when they were never really proven to start with. That's a valid point. It's the same with "miracle foods". This year, it's kale and coconut oil (I'm not really sure if you're supposed to drink the coconut oil or rub it all over yourself, but I digress). And yoghurt is supposed to fix everything. In past years it was stuff like granola and wheat germ. Something else will come along next.
I will continue to take my vitamin D and my calcium.

 

[DianaCox]

^^^ All of the things that Larra said! What I'm trying to understand is WHY they interpreted it in a way that discourages taking vitamin D supplements, when there is SO much evidence that it is helpful for so many things!

 

[southernlady]

And they are saying periodic high doses isn't as good as a steady dose. Okay, so my high dose daily is within that "criteria".

 

[Jbandmmomma]

marking this so I can come back and read the article. This makes no scientific sense to me at first glance. Initial thought is bias in patient population?

 

[Munchkin]

Another interpretation from the NHS(UK). http://www.nhs.uk/news/2016/01Janua...min-D-increase-falls-risk-in-the-elderly.aspx

Do high doses of vitamin D increase falls risk in the elderly

• vitamin D to older adults with a history of falls increased their vitamin D levels and improved leg function in comparison with the lower recommended dose – in this case, 20 micrograms (mcg) a day. This is not the recommended UK dose, which is lower still, at 10mcg.
  
  The study found the two higher vitamin D doses tested did result in a greater increase in vitamin D levels than 20mcg a day. However, it didn't have any beneficial effect on leg function – in fact, it was actually associated with an increased number of falls over the study period.
  
  This study does not provide evidence to suggest current UK government recommendations for older adults – a daily supplement of 10mcg – are "unsafe". People in the UK who currently take vitamin D supplementation as recommended should have no concerns about the results of this trial.
  
  The monthly dosage used in the highest dosage group, which had the greatest amount of falls (1,500mcg), is far higher than the recommend monthly dose of 300mcg.
  
  These findings go on to suggest that taking more than 20mcg a day of vitamin D is not beneficial for older adults.
  
  Where did the story come from?
  The study was carried out by researchers from University Hospital Zurich and the University of Basel in Switzerland, and Tufts University and the Harvard T H Chan School of Public Health in the US.
  
  It was primarily funded by the Swiss National Science Foundation and The VELUX Foundations.
  
  The study was published in the peer-reviewed medical journal JAMA Internal Medicine. The article is open access and can be read online.
  
  The Times and the Daily Mail's headlines slightly misinform the public, suggesting that taking vitamin D supplements as recommended by the government increases the risk of falls.
  
  This isn't the case. The study looked at taking higher doses than those currently recommended – these doses were associated with an increased risk of falls, not the current recommended dose.
  
  The Mail also claims the increased risk of falls could be because "the pills make patients more active, meaning they have a higher chance of falling over". This is pure speculation – the possible reasons behind the increased falls risk were not discussed in the study.
  
  What kind of research was this?
  This randomised controlled trial (RCT) aimed to examine the effectiveness of high-dose vitamin D for reducing the risk of functional decline in older adults.
  
  As the researchers say, vitamin D is believed to have a direct effect on muscle strength. Supplementation has been proposed as a way to maintain function in older adults.
  
  Several systematic reviews of previous trials are said to have consistently shown that this has a beneficial effect in preventing falls and hip fractures in those aged over 65.
  
  However, other evidence on whether it is associated with improved leg function is said to be cloudy, with some trials reporting a benefit, while others do not. A 2011 systematic review that pooled the results of 17 trials suggested the benefits were mainly limited to those with vitamin D deficiency.
  
  This trial aimed to examine the theory that high-dose vitamin D – either given alone or in combination with its breakdown product, calcifediol – would increase blood levels to at least 30ng/ml. The researchers specifically studied a higher-risk population of those aged 70 or older who previously had a fall.
  
  An RCT like this one is the best way of examining the effectiveness and safety of a treatment. However, the best evidence it will provide is for the main outcomes the study set out to look at, which in this case were vitamin D blood levels and leg function, not falls.
  
  What did the research involve?
  This 12-month study compared the effects of three different vitamin D supplementation dosages in older adults who previously had a fall.
  
  The researchers recruited adults aged 70 or over living in the community with a history of low-trauma falls in the past 12 months.
  
  Participants were also required to be mobile (with or without assistance), have normal cognitive function, and not have taken vitamin D supplementation exceeding 800 international units (IU) a day (20mcg). The final trial sample included 200 adults.
  
  Participants were randomised to one of three study groups:
  
  • group one – 24,000 IU of vitamin D taken as a 5ml drink a month, the equivalent of 20mcg a day, which is double the UK recommended dose; they also took three placebo capsules a month
  • group two – 60,000 IU of vitamin D taken as a single 5ml drink, equivalent to 50mcg a day; they also took three placebo capsules a month
  • group three – 24,000 IU vitamin D plus 300mcg of calcifediol a month taken as a 5ml placebo drink, two capsules of 12,000 IU vitamin D, and one capsule of 300mcg calcifediol
  Participants and researchers were unaware of which group they were allocated to (the study was double-blinded) as all treatments appeared identical.
  
  Participants attended three clinic visits at the start of the study and again at six and 12 months. At all visits, leg function was assessed using the Short Physical Performance Battery (SPPB) assessment, which assesses walking speed, balance and standing from a chair.
  
  Researchers also took a general history and performed an examination, and took blood and urine samples. At the start of the study and at the 12-month mark, a dual X-ray absorptiometry (DEXA) scan was also performed to assess bone mineral density.
  
  The main outcomes examined were SPPB score and the proportion of people who achieved blood vitamin D levels of at least 30ng/ml. The other outcome the researchers looked at was reported falls, which were assessed through participant diaries and monthly calls from nurses.
  
  Nine participants dropped out during the trial, but all 200 were included in the analysis. The researchers adjusted their analyses for age, gender, body mass index (BMI) and SPPB score at the start of the study.
  
  What were the basic results?
  The average age of the participants was 78, and two-thirds were women. Only 42% had adequate vitamin D blood levels at the start of the study – 58% were deficient (less than 20ng/ml) and 13% were severely deficient (less than 10ng/ml). There were no differences between the groups at the start of the study.
  
  Vitamin D blood levels increased significantly more in both the 60,000 IU vitamin D and the 24,000 IU vitamin D plus calcifediol groups at both six and 12 months. At both of these time points, a significantly higher proportion of these two groups had also achieved the target of blood levels of 30ng/ml or higher.
  
  There was no significant difference over the course of the 12 months between the three groups for changes in overall SPPB score. However, successive chair stands improved significantly more in the 24,000 IU only group than the other two treatment groups. Other functional components were similar.
  
  Overall, 60.5% of participants reported a fall during the study. The rates at 12 months were significantly higher in the 60,000 IU vitamin D group (66.9%) and the 24,000 IU vitamin D plus calcifediol group (66.1%) compared with the 24,000 IU only group (47.9%).
  
  The greater improvements in vitamin D levels in the two higher-dose treatment groups were only seen in those who had been deficient at the start of the study.
  
  Significantly more people had falls in the two high-dose groups compared with the 24,000 IU only among those who had been vitamin D deficient at the start of the study.
  
  However, when looking at the overall number of falls, more falls were seen in the two high-dose groups in people who had adequate vitamin D at the start of the study.
  
  How did the researchers interpret the results?
  The researchers concluded that, "Although higher monthly doses of vitamin D were effective in reaching a threshold of at least 30 ng/mL of 25-hydroxyvitamin D [blood vitamin D levels], they had no benefit on lower extremity function and were associated with increased risk of falls compared with 24 000 IU."
  
  Conclusion
  This trial aimed to assess whether giving high-dose vitamin D to older adults with a high risk of falls increased their blood vitamin D levels to above 30ng/ml, as well as improving their leg function.
  
  Vitamin D levels of 20ng/ml or more are generally considered adequate for bone health. But many people are deficient in vitamin D, with the elderly being particularly at risk.
  
  Current UK recommendations say people aged over 65 should take a daily supplement of 10mcg. This is the equivalent of 400 IU a day – a lower level than the lowest dose used in this study (800 IU a day).
  
  This study looked at taking two higher doses – with vitamin D alone or combined with its breakdown product, calcifediol – compared with the 800 IU a day control group.
  
  As would be expected, those in the higher dosage treatment groups had higher levels of vitamin D in their blood compared with controls. Although the higher doses led to improved leg function, they were in fact linked to a greater number of falls than seen in the control group.
  
  The trial has many strengths, including its double-blind design, the analysis of all 200 people enrolled, the relatively long duration of one year, and the use of valid assessment scales. It provides good evidence that high-dose vitamin D – alone or with calcifediol – does not benefit older adults with a prior history of falls.
  
  Taking high doses of vitamin D may also increase the risk of further falls, but this result should be interpreted with some caution – it's not the primary outcome the study set out to examine.
  
  The trial had a sufficient sample size to reliably detect differences in blood vitamin D and function score, but it may not have been large enough to reliably assess whether there were true differences in the number of falls.
  
  Importantly, though, this study does not provide evidence to suggest that current UK government recommendations for older adults are unsafe.
  
  The low-risk group in this study in terms of falls was the 20mcg a day control group. This is the recommended supplementation for older adults in the US and other countries, but not in the UK, where it is even lower, at 10mcg a day.
  
  This study also cannot tell us a lot about the effects of the dose recommended in UK guidelines, as this was not tested. Also, all the supplements were taken in the form of one big dose contained in a single drink each month, rather than as daily supplements, as recommended in the UK.
  
  And as this study is only relevant to older adults, it cannot provide any evidence on the effects of supplementation in other recommended groups, such as pregnant or breastfeeding women (10mcg a day) or young children up to five years (7-8.5mcg a day).
  
  This trial adds to the large body of evidence examining the effectiveness and safety of different forms of vitamin D supplementation in different groups.
  
  Yet people currently taking vitamin D supplementation as recommended in the UK should have no concerns.
  
  There are practical steps you can take to reduce your risk of a fall, such as removing clutter from around your home, wearing well-fitting, sturdy shoes, and doing regular strength and balance exercises.
  
  Read more about how to prevent falls.
  
  Analysis by Bazian. Edited by NHS Choices. Follow NHS Choices on Twitter. Join the Healthy Evidence forum.