Professor Tim Spector of King’s College, London has just written an article in which he says he has changed his mind about advocating the supplementation of a number of vitamins, including Vitamin D (1). First of all, he must be applauded for having the courage and integrity to admit in public that he has been wrong in the past. One of the plagues of the modern day is that far too many scientists and other health professionals refuse to accept that their pet theories are no longer valid. As a consequence they regard any criticism as a personal attack and continue to defend their position long after it has lost all credibility. So it follows that the arguments used by Tim Spector have to be taken seriously.
His doubts were raised by 2 recent papers on the effect of Vitamin D supplementation on the number of falls and on the incidence of fractures in older people (2, 3). It was found that those who were given 60,000 International Units (IUs) per month had more falls than those who were given 24,000 IUs.
Vitamin D status is assessed by the concentration of the 25-OH derivative (25(OH) D) in the blood. In order to put these results into perspective this aspect needs to be considered. The subjects in this trial were given a large dose once every month. One group was given 24,000 IUs once a month and another was given 60,000 IUs per month. It was found that those with blood levels of 110 nmol/L-240 nmol/L 25 (OH) D had the highest incidence of falls. It must be stressed that these doses are relatively high. Furthermore one large dose every month is different from having the same total amount in smaller doses taken daily. None of those who were being given 24,000 IUs had blood levels which were this high.
In the USA the Institute of Medicine (IoM) has recommended that a blood level of 50 nmol/L 25(OH) D for 97.5% of the population should be the objective. It concluded that this could be achieved if the intake was 600 IU per day. Clearly this is way below the level which was associated with the falls in the above study.
However what is highly relevant is that 2 authors of the paper quoted above, Prof. Heike A. Bischoff-Ferrari of Zurich University and Prof. Walter C. Willett of Harvard, were concerned that with respect to bone health the recommended serum levels of 25(OH) D were too low (4). They noted that:
- A threshold of 50 nmol/l (20 ng/ml) for the 25(OH) D concentration was insufficient to achieve a reduction in the incidence of falls or fractures in treatment groups.
- Furthermore, in the very large population-based NHANES analysis, bone density increased with higher 25(OH)D levels far beyond 50 nmol/l (20 ng/ml) in younger and older adults suggesting that the IOM threshold recommendation is too low for optimal bone health in adults.
- The International Osteoporosis Federation had recommended that the Vitamin D intake should be 800 to 1000 IU for people aged 60 years and over in order to achieve a serum 25 (OH) D level of 75 nmol/L. This was considered optimum for the limitation of falls and fractures.
They go on to comment:
“The IOM conclusion that intakes of vitamin D are adequate for most of the US population assumes that lack of randomized trials means lack of benefit, which seems illogical.”
One wonders what their view would be of the recommendation of the Scientific Advisory Committee on Nutrition (SACN) in the UK which has decided that 25 nmol/L 25(OH) D would be suitable for the population of the UK and the Recommended Nutrient Intake (RNI) should be 400 IU per day. This appears to be unbelievably complacent and is only half the value which the IoM advises.
Tim Spector’s doubts were reinforced by an “umbrella review” in the BMJ which was based on over 250 reviews/meta-analyses (6). This concluded that there is highly convincing evidence for a clear role of Vitamin D does not exist for any outcome, but associations with a selection of outcomes are probable. In other words, the researchers were unable to find any convincing evidence, especially randomised controlled trials (RCTs) which proved conclusively that there was a definite improvement in those individuals who had an increased intake of the vitamin.
As usual, readers were able to respond to this article and many of them had reservations about the conclusions and significance of this paper. The points made include the following:
- Many of the studies cited did not take precautions to ensure that those with an adequate supply of Vitamin D were excluded. Clearly such participants would not be expected to respond positively.
- Inadequate numbers in some of the trials.
- Failure to have a high enough dose of Vitamin D.
- Failure to allow for the role of other minerals and vitamins including Vitamin A, Vitamin K2, calcium and magnesium.
- The tissue damage related to a specific aspect if ill-health may not be reversible and therefore not effect would be detected.
One of the respondents noted that one of the co-authors of the umbrella review, John Ioannidis, has concluded in an earlier paper such reviews should be regarded as:
“subjective and suboptimal”,
“limited by the data in the primary studies” and the process of
“patching together pre-existing reviews”.
This means that they are open to subjective interpretations based on the authors’ opinions. The respondent, Simon Spedding, commented that:
“The reason Vitamin D meta-analyses and reviews fail to produce useful results is thought to be biological flaws in primary studies… These flaws lead to null results as the intervention does not change the Vitamin D status; however these flaws may be overlooked when evaluating the research for Vitamin D and other nutrients…”
“The review authors… describe flaws as “difficulties in relation to RCTs” such as “low dose vitamin D supplementation”, “large differences in baseline plasma concentrations of 25-hydroxyvitamin D” and “contamination with private use of vitamin D” in the randomised controlled trials that might be “inadequate to raise the body’s vitamin D concentrations enough to show a difference between the arms of a trial”…Whilst this umbrella review… recognised these “difficulties” or biological flaws in their primary studies, the authors choose not to compare meta-analyses of flawed and unflawed primary studies.”
Despite these concerns raised by Tim Spector the fact remains that there is compelling evidence from a variety of different sources and disciplines which indicates that in many people there is an insufficiency of Vitamin D. Therefore it would be beneficial for them to increase their intake.
The findings that there is an increased incidence of falls reported in the study are likely to be genuine but closer examination shows that the blood levels in those affected are very much higher than in the vast majority of the general population. It is possible that the single high dose causes particular problems in the group of older people. Undoubtedly such high levels in the blood should be avoided and it is important to discover why that occurred in this investigation. Nevertheless there is absolutely no doubt that in many people the Vitamin D status is far too low and nowhere near that reported in the study. There is no question that current official recommendations in the UK, which are only 50% of those in the USA, are totally inadequate. But there are also valid reasons for believing that the USA recommendation should be increased.
So while I respect Tim Spector for his honesty and integrity, I suspect that he has failed to appreciate the weaknesses in the papers which have caused him to change his mind. It also appears that he has discounted the excellent work of a number of key players, such as Michael Holick (6), who have made valuable contributions to our understanding of the crucial role of Vitamin D in the body.
- S R Cummings et al (2016) http://archinte.jamanetwork.com/article.aspx?articleid=2478893
- H A Bischoff-Ferrari et al (2016) http://archinte.jamanetwork.com/article.aspx?articleid=2478897
- E Theodoratou (2014) http://www.bmj.com/content/348/bmj.g2035
- M F Holick (2010) “The Vitamin D Solution: A 3-Step Strategy to Cure Our Most Common Health Problems” Plume (Penguin) New York