Context of this post
Many newspapers and broadcasters gave extensive coverage to new advice from Public Health England (PHE) recommending increased use of vitamin D supplements. PHE recommended that most adults and school age children should take a daily dose of 10μg (400i.u.) of vitamin D during the winter and autumn months and that younger children, those with pigmented skin and those whose skin gets little sun exposure (like the housebound elderly) should take these supplements all year round. This new advice follows publication of a very extensive 300 page report on “Vitamin D and Health” from the government’s Scientific Advisory Committee on Nutrition SACN.
My personal assessment
I find myself in the rather odd position of supporting the advice from PHE but paradoxically having no confidence that it will make any significant impact upon the population’s nutritional status for vitamin D. This is because I believe that over-the-counter supplements are a very ineffective way of improving vitamin or mineral status of a population. The following examples illustrate this point.
- Even though a third of us take supplements, millions of British people have inadequate intakes of one or more vitamins or minerals or show biochemical evidence (i.e. blood analysis) of poor nutrient status. If the number of people classified as having inadequate intake of any vitamin or mineral from food is calculated, this number is not significantly altered if supplemental intakes are then added in. This is because supplements are almost always taken by those with good nutrient intakes from food and hardly ever taken by those who really need them. Supplements raise the intakes of those with already high intakes, so although they raise average intakes they do not increase the intakes of those with low or inadequate intakes. Webb’s rule of supplements: “if you take an over the counter supplement you almost certainly don’t need it”.
- Recommending that women take folic acid supplements when planning a pregnancy did not affect rates of spina bifida and other neural tube defects (NTD) in Europe in the six years after the recommendation was first made in 1992. This is despite the fact that these supplements clearly work in clinical trials (Botto et al, (2005).
I think that if there is to be any significant improvement in vitamin D status of the British population then we will probably need to add vitamin D to a staple food like flour. It is possible that a national campaign to encourage supplement usage and highly pro-active efforts to get free supplements to those most at risk might also have an impact. I have very little confidence that any British government will take such decisive actions. Many countries around the world have followed the example of the USA and Canada in 1999 and added folic acid to flour or bread and this has led to immediate falls in rates of NTD. Expert groups have been recommending this in Britain for almost twenty-five years but still successive governments dither.
Nature and functions of vitamin D
Vitamin D is a fat soluble vitamin that is unique in that most of a healthy person’s vitamin D is made within the body from scratch. People and animals produce a substance in their skin (7-dehydrocholesterol) that can be converted to vitamin D3 when the skin is exposed to ultra-violet light. The correct UV wavelengths are only found in summer sunlight at UK latitudes. Provided the skin is adequately exposed to summer sunlight then, unlike any other vitamin, there is no dietary requirement for vitamin D.
There are few good food sources vitamin D. Modest amounts are present in liver, whole milk, cheese, butter, fortified breakfast cereals and fortified margarine and low fat spreads. Oily fish like herring, salmon, mackerel and sardines are relatively rich sources as is cod liver oil. Yeast and fungi which have been irradiated with UV light contain an alternative form, vitamin D2 and this has been a useful source of the vitamin for use in supplements and food fortification. Wild mushrooms provide some vitamin D but not cultivated mushrooms which are grown in the dark.
Vitamin D itself is biologically inactive and has to undergo chemical conversion (hydroxylation) before it becomes active. In the liver, vitamin D is converted to 25-hydroxyvitamin D (25OHD) which is the stable circulating form of the vitamin and levels of this substance in blood are used to assess vitamin D status. In the kidney, this 25OHD is converted to an active hormone 1,25-dihydroxyvitamin D or 1,25(OH)2D. This active hormone produced in the kidney is known to play a key role in the absorption and reabsorption of calcium in the gut and kidney and is essential for the development and maintenance of strong, healthy bone. The mechanical strength of bone is largely due to its mineral content which is a complex mixture of calcium and phosphate.
There has been considerable speculation that vitamin D may be involved in regulating processes outside of bone partly because of the presence of receptors for 1,25(OH)2D on many cells that play no obvious role in calcium metabolism like cells of the immune system, skin cells and several cultured tumour lines. The European Food Safety Authority (EFSA) has been tasked with assessing which claims about foods and supplements producers are permitted to make use of on their packaging and when promoting their products. They reject the majority of these claims because of lack of sufficient evidence but with respect to vitamin D they concluded that:
“A cause and effect relationship has been established between the dietary intake of vitamin D and contribution to the normal function of the immune system and healthy inflammatory response, and the maintenance of normal muscle function”.
The effects of vitamin D deficiency
Severe vitamin D deficiency in children causes rickets, a disease that at the turn of the 20th century affected the majority of poor children living in some industrial cities of Britain, Northern Europe and some cities like Boston in the northern part of the USA. A range of social, cultural and public health measures like those listed below succeeded in essentially eradicating rickets in Britain in the decades after World War II:
- Children were able to spend more time outside
- Reduced air pollution allowed more sunlight to penetrate
- Fortification of margarine and infant formula with vitamin D
- The provision of free cod liver oil to mothers and babies.
Children with rickets have soft bones because of inadequate availability of calcium to produce bone mineral and this gives rise to a whole range of skeletal problems like bone pain, poor growth, increased fractures and a number of skeletal deformities including bow legs or knock knees. Other symptoms include muscle weakness and tetany (muscle spasms) caused by low blood calcium concentration. Children with rickets are also prone to infection but it is not clear whether this is a direct effect of the vitamin D deficiency.
Vitamin D deficiency in adults leads to a condition called osteomalacia and this condition causes bone pain, increased fracture risk, bone deformity, muscle weakness and an abnormal waddling gait. Blood calcium levels are low and tapping the face near the jaw hinge causes muscle twitching at the corner of the mouth (Chvostek’s sign).
Osteoporosis is condition where there is progressive loss of bone density and strength in older people especially in women after the menopause. This loss of bone strength increases risk of fractures of the wrist, vertebrae and most significantly of the hip. Chronic vitamin D and/or calcium deficiency is probably a risk factor for osteoporosis because low blood levels of calcium lead to increased secretion of parathyroid hormone which releases calcium from bone mineral to maintain calcium levels in the blood.
Defining vitamin D inadequacy
One complicating factor when trying to assess requirements for vitamin D (from the diet, supplements or self-produced) is the dietary intake of calcium. A major role of vitamin D is to increase calcium uptake from food so high calcium intakes may compensate for low vitamin D status and vice versa.
In the UK, a plasma level of 25nmol/L of 25OHD has traditionally been taken as the cut-off point for vitamin D adequacy and values below this threshold are classified as inadequate. Blood plasma levels below this are increasingly likely to lead to rickets although most people at or below this level will not have rickets. In order to achieve this blood level from the diet then an intake of around 10μg/day would be required which is around four times actual average UK intakes. Even those with the highest intakes from food would probably not regularly take in 10μg/day. Up until now it has been assumed by the UK experts who set dietary standards, that most adults and school age children will make this amount of vitamin D themselves and so will not be dependent upon a dietary supply. Dietary standards (in the range 7-10μg/day) have thus only previously been set for pre-school children, the elderly and women who are pregnant or lactating.
A different approach has been taken in the USA, where dietary standards have been set on the basis that there is relatively little contribution from sunlight to vitamin D in the body. In 2001, American standards were set at 15μg/day for those under 70 years rising to 20μg/day for those over 70 years. These intakes aim to achieve a plasma level of around 50nmol/L of 25OHD i.e. double the threshold of adequacy set in the UK. Average intakes of vitamin D in the USA are around double those in the UK largely because more foods, especially milk, are fortified there. The Endocrine Society, a scholarly scientific society in the USA, has suggested that the optimum plasma level of 25OHD should be 100-150nmol/L which would require a daily intake or production of around 25μg/day.
How prevalent is vitamin D deficiency in the UK?
The most obvious indication that vitamin D deficiency is a problem in the UK is the small but rising number of hospital admissions for rickets, in 2012-13 there were 833 recorded admissions compared with just 190 ten years earlier. The British Paediatric Surveillance Unit began a survey in March 2015 to assess the true prevalence of rickets and to collect information about the condition and its treatment. Black and Asian children are greatly over-represented in diagnosed cases of clinical rickets. One would expect that such severe clinical cases would represent the “tip of the iceberg” with many more children impaired to a lesser extent e.g. increased risk of bone fractures and muscle weakness.
Since 1992, plasma levels of 25OHD have been routinely measured in large National Diet and Nutrition Surveys (NDNS). These surveys indicate that a large proportion of people in all age groups have serum levels below the threshold of adequacy (25nmol/L) used in the SACN report with 30-40% below this level in the winter months. Almost 40 % of the institutionalised elderly were below this level. Some figures for the proportion of people below this threshold are given in the table below.
Table The percentage of British people below the 25nmol/L threshold for 25OHD with seasonal variation (figures from NDNS).
Age group (years) Jan-Mar (%) July-Sept (%)
4-10 31 2
11-18 40 13
19-64 39 8
65+ 29 4
For some groups, the number below the threshold remained high even in the summer months e.g. Scottish adults (17%), London adults (16%) and South Asian women in Southern England (53%).
If the higher threshold of 50nmol/L favoured by the Institute of Medicine in the USA was taken then 40-60% of the population and as many as 75% of young adults, the elderly and British Asian children would be below this level with even higher proportions in the winter months (Prentice, 2008).
Potential benefits of improving vitamin D status
Many people in all age groups have poor biochemical status for vitamin D and cases of clinical rickets are increasing. This would seem to be clear justification for trying to improve vitamin intakes in the UK. In their detailed report, the SACN committee evaluated the evidence for many claimed potential benefits for increased vitamin D intakes. They made their recommendations because they felt that there was firm evidence that this would improve musculoskeletal health i.e. reduce the incidence of rickets and osteomalacia, reduce falls and increase muscle strength and function. For many of the other claims they considered that the evidence was not sufficiently strong as a basis for making population wide recommendations.
One of the most persistent and most studied of the claims for vitamin D supplements is that they will reduce fractures in older people, especially elderly women, that are due to osteoporosis. Hip fractures in particular are a major public health problem in the UK which not only cause much distress, disability and many premature deaths amongst older people but soak up huge amounts of NHS resources. The National Osteoporosis Society estimate that there are around 70000 hospital admissions and £1.5 billion in direct costs to the NHS as a result of osteoporosis-related fractures. There have been many clinical trials of vitamin D supplements to assess their impact on fracture risk and several meta-analyses where these clinical trials have been combined to try to get a summation of their findings. These trials have produced mixed results which make it difficult to draw firm conclusions. Amongst the factors that might influence the outcome of such trials are:
- The dose of vitamin D used
- Whether or not calcium supplements are also given
- The vitamin D status of the subjects at the outset
- The age of the subjects
- The state of the patients’ bones at the outset of the trial which will be partly dependent upon age.
There is no evidence that vitamin D supplements are beneficial if subjects have already experienced an osteoporosis-related fracture. Some individual trials in fracture-free elderly people suggested that vitamin D supplements reduce fracture whilst some have suggested no statistically significant effect. In a meta-analysis by Alison Avenell and her colleagues in 2014, when nine studies of vitamin D alone were combined there was no significant detectable benefit of the supplements on fracture rates but when eight trials of combined vitamin and calcium supplements were amalgamated then there was a significant effect primarily due to reduced rates in frail, institutionalised, elderly people. These trials have used different doses of vitamin D and there is some suggestion that those using the higher doses have produced the more positive effect. One effect of combining calcium with vitamin D supplements may be to have an effect similar to increasing the dose of vitamin D. Improvement in vitamin D status and optimising bone health throughout life may be more effective in preventing fractures than giving supplements to elderly people to compensate for poor vitamin D status throughout the earlier parts of their lives.
In addition to effects upon the skeleton and muscles, there are many other claims for beneficial effects of vitamin D based upon varying levels of circumstantial evidence. As noted earlier, the EFSA concluded that vitamin D does play a role in the functioning of the immune and inflammatory systems and this would suggest that vitamin D inadequacy would adversely affect the functioning of these systems. Many of the non-musculoskeletal claims about vitamin D relate to conditions involving abnormal functioning of the immune or inflammatory systems. Just to get an idea of the range of vitamin D claims, I searched for vitamin D related articles on the BBC news web-site and got well over 100 hits before I stopped counting. A selection of the headline claims are listed below and they indicate that there is a high level and very wide range of research into the potential impact of vitamin D inadequacy or the effects of vitamin D supplements.
Vitamin D “slashes cancer risk”
Vitamin D “heals damaged hearts”
Vitamin D “boosts child muscles”
Vitamin D boosts cancer treatment
Vitamin D “key for healthy lungs”
Vitamin D pills cut MS* risk
Vitamin D reduces risk of diabetes
Parkinson’s linked to vitamin D
Vitamin D could cut arthritis
Vitamin D deficiency linked to dementia
Sunshine vitamin may treat asthma
Sun’s blood pressure benefits “may outdo cancer risk”
(*MS = multiple sclerosis)
In a short piece like this I am not going to try to evaluate each of these or other claims but I will give a flavour of some of the reasoning behind a few of them and some of the limitations of the existing evidence. The SACN report did make some evaluation of many of them and found that some seemed to be unlikely and many others were as yet only supported by relatively low level evidence.
There is strong evidence from cohort studies that having a low blood level of 25OHD is fairly consistently associated with increased risk of dying during the course of the study. This may indicate a protective effect of good vitamin D status but an alternative explanation is that low blood levels of 25OHD are an indication of existing poor health e.g. inactive and frail people or people with unhealthy lifestyles may be less likely to spend time outside in the sun. Evidence from studies with supplements is less convincing; overall supplements that included vitamin D did reduce total mortality but when those that also included calcium were excluded, this effect was no longer statistically significant. Similar results and arguments can be made when serum 25OHD are related to some specific causes of death.
Incidence of several autoimmune diseases (e.g. multiple sclerosis and type I diabetes), hypertension and some cancers increases with increasing latitude i.e. with reduced sunlight exposure. Migration studies tend to be consistent with a protective effect of Vitamin D (more sunlight exposure) on risk of MS. At any given latitude, higher altitude (i.e. with stronger sunlight) is associated with reduced MS incidence. There are several studies suggesting that extra vitamin D may reduce incidence or progression of diabetes and an MS-like condition in animal models. Finally there is some intriguing research from a group in Oxford suggesting a link between inheritance of a defective gene involved in the activation of vitamin D and increased risk of multiple sclerosis which would be consistent with a causal link between vitamin D deficiency and increased risk of MS. I should stress that the SACN committee were unconvinced by the evidence that vitamin D deficiency might be a cause of multiple sclerosis.
The case for adding vitamin D to a common food (flour or milk)
The authors of the SACN report have concluded that there is a strong case for trying to improve the vitamin D status of the UK population. There are four main ways in which improved status for vitamin could theoretically be achieved.
- Consumption of more foods that are naturally rich in vitamin D. There are few naturally rich dietary sources of vitamin D and food currently contributes only a small fraction of vitamin D needs in the UK. Dietary changes that are consistent with other dietary objectives and that would bring about the necessary increases in vitamin D intakes are impractical and unachievable.
- Increased skin exposure to summer sunlight. Most of the health promotion guidance relating to sunlight exposure has focused upon reducing the risk of sunburn, skin ageing and skin cancer. Whilst it may be possible to produce guidelines on sunlight exposure that improve vitamin D status without increasing risk of skin damage and cancer, this guidance is likely to be quite complex. Adequate sunlight exposure will depend upon factors like skin pigmentation level, age, sunscreen use, latitude and season so it may be difficult to give simple and clear population guidelines for sunlight exposure that are consistent with these conflicting aims. There may nevertheless well be a case for trying to modify the balance of the health promotion message which currently seems to focus upon sunlight exposure as wholly negative in its health implications.
- Increased use of vitamin D supplements. Vitamin supplements superficially seem to be an ideal solution for vitamin or mineral deficiencies but simply encouraging use of over-the-counter supplements is unlikely to be effective. Intensive focused campaigns with liberal use of free supplements might have more impact but will require considerable investment of resources that are unlikely to be forthcoming.
- Adding vitamin D to flour (or milk). Fortification of a common food is probably the cheapest and most effective method of improving intake of a nutrient across the population. It played a significant role in eradicating pellagra (vitamin B3 deficiency) in the USA, eradicating goitre and cretinism (iodine deficiency) in Switzerland and parts of the USA and in reducing incidence of neural tube defects like spina bifida in many countries including the USA and Canada. In the USA milk has been fortified with vitamin D since 1932 and played a role in the eradication of rickets.
For the most vulnerable e.g. frail, institutionalised elderly people then occasional depot injections of slow-release vitamin D might be considered as another option.
Is fortification with vitamin D safe?
Several national and international agencies have suggested tolerable upper limits (UL) for vitamin D i.e. the highest daily intakes that is likely to pose no adverse risk to nearly everyone in the population. Back in 2003, a UL for vitamin D of 25µg/day was suggested in the UK. Since then both the Institute of Medicine (IOM) in the USA and the European Food Safety Authority (EFSA) have re-assessed the UL for vitamin D. The EFSA set a UL of 100µg/day for all adults and children over the age of eleven years with lower levels for younger children and infants. The IOM also chose 100µg/day for adults but did suggest that doses of more than double this level were unlikely to produce symptoms of toxicity. The SACN committee agreed that the UL set by the EFSA were appropriate for the UK:
- All adults and children 11+ years – 100µg/day (4000i.u.)
- Children 1-10 years – 50µg/day (2000i.u)
- Infants – 25µg/day (1000i.u.)
Average UK intakes from food are around 2-3µg/day and maximum intakes less than 10µg/day so there is a very large safety margin of around 10 fold between current maximum intakes and potentially toxic levels. This means that there is considerable scope for safely fortifying UK food with extra vitamin D. Those taking large supplemental doses might theoretically be at risk but even then the contribution of fortified food to any potentially toxic dose would be very small.
Note that excessive exposure of the skin to sunlight does not cause vitamin D overdose because production in the skin is regulated.
There is clear justification for measures to improve the vitamin D status of the British population. The most effective way of achieving this quickly, cheaply and safely would be if there was almost universal fortification of a core food like bread with vitamin D. Marks and Spencer announced in May 2015 that it was acting unilaterally to fortify its bread with vitamin D. Almost universal fortification could be achieved if bread manufacturers were officially recommended to fortify their products and required to label any unfortified product as not compliant with government recommendations. This would allow unfortified bread to still be sold as an option for people who choose or need to avoid the fortified products. Market forces should ensure that fortified bread acceptable to vegetarians would be available.
To coincide with the introduction of fortification, the government should commission an intensive programme of surveillance and monitoring to assess its impact. Certain benefits as discussed earlier would be confidently expected to follow the improvement in the vitamin D status of the population. There could also well be other benefits if any of the many other health claims for vitamin D prove to be correct. This surveillance should give early warning or more probably reassurance about any unanticipated adverse consequences of fortification. This surveillance programme could make a major contribution to clarifying the health benefits of ensuring good vitamin D status throughout the lifespan.