Is a vitamin D fortification strategy needed?

Abstract

Almost one in five adults aged 19–65 years in the UK has a low serum vitamin D concentration (below 25 nmol/l) according to the National Diet and Nutrition Survey (NDNS) (Roberts et al. 2018), which puts them at increased risk of the manifestations of vitamin D deficiency, described below. In some age groups, prevalence is even higher; for example, 39% among adolescent girls aged 11–18 years. Government recommendations in the UK emphasise the importance of ensuring adequate vitamin D for everyone to protect bone and muscle health. Public Health England (PHE) advises that adults and children over the age of 5 years require an average of 10 µg of vitamin D a day and should consider taking a daily supplement during autumn and winter (a combination of diet and sunshine exposure is sufficient for most people during the spring and summer provided they spend time outside). There is also specific advice for the under-fives (Table 1). People who have a higher risk of vitamin D deficiency are being advised to take a supplement all year round (Table 1). In April 2020, PHE reissued its advice on vitamin D, recommending that whilst the stay at home coronavirus measures are in place, everyone (including children, pregnant and breastfeeding women and older people) should consider taking a daily supplement containing 10 μg of vitamin D, even during the summer months, if they are not going outdoors often (NHS 2020). But is the general advice on vitamin D supplement usage being adopted and, if this approach fails, what might plan B look like? 8.5 to 10 micrograms of vitamin D a day, throughout the year. Babies consuming more than 500 ml infant formula per day do not need any additional vitamin D as formula is already fortified. Most people, other than those in at-risk groups, probably get enough vitamin D from being outdoors and consuming vitamin D-containing foods. During the winter months, most people rely on dietary sources of vitamin D. Vitamin D is found naturally in a small number of foods, for example oil-rich fish, red meat, liver and egg yolks. It is also present in fortified foods, for example breakfast cereals, most fat spreads and in food supplements. Consider taking a daily supplement. At-risk groups include: These individuals should take a daily supplement throughout the year, containing 10 micrograms of vitamin D. These individuals may not get enough vitamin D from sunlight and should consider taking a daily supplement containing 10 micrograms of vitamin D, throughout the year. In September 2019, a Forum was convened, with funding from the Rank Prize Funds, to explore the current situation and options for implementation strategies for increasing vitamin D intake across the distribution of food consumption patterns in the UK. The Forum discussed the potential of food fortification as a strategy, using learnings from the pan-European ODIN study (Kiely & Cashman 2015; Kiely & Cashman 2018). Since the Forum took place, the coronavirus pandemic has placed a spotlight on the potential of good nutrition to promote immune function (www.nutrition.org.uk/healthyliving/helpingyoueatwell/covid19immunity.html) and, in this context, the association between low vitamin D status and reduced immune response has been flagged. Ill-informed advice about very high and potentially harmful vitamin D supplementation, which lacks an evidence base, has been circulating on social media (for a commentary see Lanham-New et al. 2020). Nevertheless, the fact remains that many people around the world are ‘staying at home’ and as a result may have less opportunity for sunlight exposure than usual during the spring and summer months, highlighting the importance of following government advice on vitamin D supplementation (10 µg/day is recommended in the UK, Table 1) and on consuming dietary sources as a means of achieving adequate vitamin D status. The government's reissued advice emphasises that even during the summertime, people who are not able to get outside much should consider taking a 10 µg daily supplement of vitamin D. The advice stresses that the recommendation is not about preventing coronavirus (COVID-19) or mitigating its effects; vitamin D is needed to keep bones and muscles healthy. Vitamin D is a generic name for two different compounds, ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3). Vitamin D3 can be obtained from the diet and by endogenous synthesis in the skin via the action of UVB radiation (290–315 nm), which converts 7-dehydrocholesterol to vitamin D3, whereas vitamin D2 is obtained solely from the diet. Vitamin D2 is naturally present only in fungi (e.g. wild mushrooms or UVB-treated cultivated mushrooms, and UVB-treated yeasts). There are relatively few dietary sources of vitamin D3, the richest being oil-rich fish and egg yolks. Other sources include meat/meat products and fortified foods, such as some fat spreads, some breakfast cereals, some dairy products (especially yogurts) and vitamin D fortified dairy alternatives. In 1940, the vitamin D fortification of margarine became mandatory in the UK (see DH 1991) but this requirement ceased in 2013 (Defra 2014). In some countries (e.g. the US and Canada), liquid milk is fortified routinely but this is not the situation in the UK. In 2016, the UK’s Scientific Advisory Committee on Nutrition (SACN) published a full risk assessment on vitamin D that involved a review of the evidence concerning vitamin D and a wide range of health outcomes (SACN 2016). The strongest evidence concerned the prevention of rickets, osteomalacia and falls, and benefits for muscle strength and muscle function in adults ≥50 years. This evidence was used by SACN to develop dietary reference values for the UK population. Insufficient evidence was found for vitamin D in relation to non-musculoskeletal outcomes such as cancer, cardiovascular disease, autoimmune diseases, infectious diseases and cognitive function. Of relevance to the current coronavirus pandemic, a possible role of vitamin D in modulating the immune response to infectious diseases has been suggested by the presence of vitamin D receptors and an enzyme associated with vitamin D metabolism (1α-hydroxylase) in various cells of the immune system including B- and T-lymphocytes, macrophages and dendritic cells (SACN 2016). Support for an immunomodulatory role has also been suggested by ecological studies showing associations between seasonal variations in serum 25(OH)D concentration and incidence of various infectious diseases including respiratory infections. While findings from cohort studies are generally supportive of an inverse association between serum 25-hydroxyvitamin D [25(OH)D] concentration and respiratory tract infections, findings from randomised controlled trials (RCTs) have been inconsistent (SACN 2016) and further research is urgently required (Lanham-New et al. 2020). Clinical musculoskeletal manifestations of poor vitamin D status are osteomalacia (adults) and nutritional rickets (children). Characterised by poor bone mineralisation, pain, deformities and fractures, these conditions are caused by low calcium intakes and/or vitamin D deficiency. It is of concern that the incidence of hospital admissions due to rickets in England increased between 2000 and 2011 (Goldacre et al. 2014), and a 2-year survey (2015–2017) suggested an annual incidence of nutritional rickets of 60 cases per year, with the greatest number in infants aged 12–23 months who were of Black or Asian ethnicity (Julies et al. 2020). Several of the infants sadly died as a result of dilated cardiomyopathy. The nature of the survey meant that it did not capture cases seen in primary care or those seen by general practitioners; Uday and colleagues suggest that these nutritional rickets cases presenting to secondary care are only the tip of the iceberg of hidden and widespread vitamin D deficiency (Uday & Hogler 2018). Nearly 80% of the cases were not taking the recommended vitamin D supplements. The most recent data from the NDNS (Roberts et al. 2018), derived from measurements taken in 2014–2016 and, therefore, measured before PHE’s advice on vitamin D supplementation, revealed that the main dietary contributors for adults and children over 1 year of age were cereals/cereal products (including fortified breakfast cereals), meat, fish, fortified milk/milk products, eggs and fat spreads, but their relative contributions varied with age (Table 2). Fortified milk/milk products were a major contributor for young children but this food group made a smaller contribution in older children and adults. Conversely, the contribution from meat and fish was higher in adults. The main dietary contributors for infants under 1 year of age were infant formula and commercial infant foods, meat, fish, eggs, fat spreads and cereals/cereal products. Synthesis of vitamin D following exposure of the skin to UVB radiation is the predominant source of the vitamin for most people in the UK during the summer months (April to September). This is likely to be May to September in the most northern parts of the UK. As already mentioned, foods that naturally provide vitamin D are few but it is added as a fortificant to some food categories such as breakfast cereals, spreads and milk products, and vitamin D supplements provide another option. Average daily intake of vitamin D, among adults, from foods and supplements combined is 4.5 and 3.9 µg, respectively, in men and women (aged 19–64 years) and 5.1 and 6.2 µg, respectively, in men and women aged 65 years and older (Roberts et al. 2018). For many population groups and individuals in the UK, achieving an average of 10 µg/day will require supplementation yet the UK is not a nation of supplement users. For example, a minority (less than a third) of women of childbearing age adhere to the advice to take folic acid supplements despite the well-publicised benefits for prevention of neural tube defects in offspring (SACN 2017). Less than 20% use vitamin D supplements and, even in high-risk groups, usage is relatively low. Despite advice for at-risk groups to take a daily 10 µg supplement throughout the year, only 23% of men and 39% of women of South Asian ethnicity (aged 40–69 years) in the UK Biobank cohort took vitamin D supplements and the median intake from diet was low (between 1.0 and 3.0 µg) (Darling et al. 2018). Vitamin D is converted in the liver to 25(OH)D, blood concentrations of which are used to assess vitamin D status. In the kidney, 25(OH)D is converted to the active form of the vitamin, 1,25-dihydroxyvitamin D, which acts in combination with parathyroid hormone and calcitonin to maintain calcium and phosphate homoeostasis. To maintain adequate serum or plasma levels of 25(OH)D and hence avoid vitamin D deficiency, SACN recommended a daily reference nutrient intake (RNI) of 10 µg/day. This was modelled on the basis of maintaining population protective 25(OH)D concentrations in serum or plasma of ≥25 nmol/l throughout the year; below this concentration, the risk of poor musculoskeletal health increases. The plasma concentration of 25(OH)D reflects the combination of dietary intake, UVB exposure and biological reserves of vitamin D. The available data from UK dietary surveys show that, averaged across the seasons, mean serum or plasma concentrations of 25(OH)D were above the population protective level of 25 nmol/l in all age groups. The percentage of infants with a serum or plasma 25(OH)D concentration below 25 nmol/l was 6% (infants aged 5–11 months) and 2% (12–18 months of age). It is noteworthy that sampling among infants was weighted towards the summer months when 25(OH)D concentrations would be expected to be higher (Lennox et al. 2013). In comparison, a greater proportion of children (aged 4 years and over) and adults had plasma 25(OH)D concentrations below 25 nmol/l (Roberts et al. 2018). In particular, 39% of girls and 15% of boys aged 11–18 years were below the threshold, while 19% of men and 16% of women (aged 19–64 years) and 11% of men and 15% of women (aged 65+ years) also had a plasma 25(OH)D below 25 nmol/l (these results are averages of samples collected across all seasons of the year). SACN reported that mean plasma 25(OH)D concentration was lowest in winter and highest in summer. On average, around 30–40% had concentrations below 25 nmol/l in winter compared to 2–13% in summer but a substantial percentage of some population groups did not achieve a plasma concentration ≥25 nmol/l even in summer (17% adults in Scotland, 16% adults in London, 53% of women of South Asian origin living in the south of England and 29% of pregnant women in a study in North West London) (SACN 2016). Endogenous synthesis is only possible during spring and summer at UK latitudes; during autumn and winter in the UK, vitamin D has to be obtained exclusively from the diet (including vitamin D supplements). Some at-risk groups with little or no skin exposure to sunlight during spring and summer, such as those who do not go outside often or who cover most or all of their skin, are reliant on dietary sources of vitamin D throughout the year. Furthermore, minority groups with skin may not get enough vitamin D from sunlight exposure during the summer months present in skin the of skin synthesis et al. it is not that low vitamin D status is more among some minority groups living in the UK than in the population. The Health Survey for England reported that Asian years) had a mean 25(OH)D status nmol/l) than nmol/l) In a study of South Asian women living in the south of mean 25(OH)D concentrations were relatively low and at around the 25 nmol/l throughout all seasons of the year, with 53% of women not achieving a concentration nmol/l during the summer months (Darling et al. 2013). from the UK Biobank cohort show a situation in of South Asian ethnicity (Darling et al. 2018). The potentially of nutritional rickets in are yet it is that UK government advice on vitamin D supplementation is not all This emphasises the importance of routinely and to the need for supplementation, with this advice being and groups and via groups. The strategies may to be of the most at-risk groups. During the it was suggested that the need for and advice in Table 1) to have to an by some which may be to about the of the Public Health advice not include specific recommendations for population advice about UVB exposure and fortified foods It is to that most foods that naturally vitamin D are of origin and are food sources of vitamin It is in vitamin D that concern about the vitamin D status in this group may in of the recent among and adults to a of combined with current for vitamin D in this age group low vitamin D status is already in 39% of adolescent NDNS data to intakes among and is to be to the relatively small percentage of these groups the population as a to be around and respectively, and present in the NDNS Several during at the in over it that has been in the vitamin D what might plan B look of the Forum will be published et al. but a of some of the is provided potential strategies for poor intakes have been by the Health and the and of the increasing the of foods food fortification and supplementation of sunlight exposure during the summer months, potentially has a to in the widespread prevalence of vitamin D As in the of the current coronavirus pandemic, dietary (including is for those for sunlight exposure is for strategies include: is to be supportive food and health of the importance of vitamin D (including of the of vitamin D and of government advice on vitamin D across the health and social care with via the food the of food and in and in vitamin D status is not a to the UK, concentrations of 25(OH)D below nmol/l are relatively in and is a higher risk of low vitamin D status among some minority groups. The on the is increasing the of foods but this has its are very few food sources naturally in vitamin D. These are of which is in the of the recent for a of the food with on increased consumption of foods and in foods for as of a more diet (see & 2020). The have that food fortification has potentially the and most and is generally to be more than other trials with added vitamin D in the (e.g. to meat or food studies and data from and dietary studies that dairy products, and eggs be fortification and that fortification strategies vitamin D intake across the distribution of population intakes and hence the risk of deficiency (Kiely & Cashman 2018). Vitamin D3 is more than vitamin D2 for plasma 25(OH)D which has for of fortificant et al. et al. 2017). The ODIN a of that of the potential of fortification strategies research to 25(OH)D status. ODIN also modelled consumption of fortified foods might to a risk of the intake level for vitamin D of µg/day The that consumption of a combination of fortified and foods did not a risk at the of the those taking vitamin D supplements (e.g. in to fortified foods would be to the Furthermore, in summertime, endogenous vitamin D synthesis in individuals with exposure is when combined with fortified foods this would not be expected to to exposure to vitamin D this to be While the evidence a from one of the greatest is to take to in a research and them in a a by et al. 2013). 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