New perspectives on vitamin D food fortification based on a modeling of 25(OH)D concentrations
- Jonathan Brown†1,
- Arne Sandmann†1,
- Anita Ignatius2,
- Michael Amling1Email author and
- Florian Barvencik1
© Brown et al.; licensee BioMed Central Ltd. 2013
Received: 26 July 2013
Accepted: 18 November 2013
Published: 21 November 2013
In Germany, vitamin D intake from food and synthesis in the skin is low, which leads to low 25(OH)D serum concentrations. In contrast to many other countries, general vitamin D food fortification is still prohibited in Germany, although the European Commission published a regulatory framework to harmonize addition of vitamins to foods. Thus the purpose of our study was to develop a vitamin D fortification model, taking into account all vitamin D sources with the goal to fulfill requirements of intake recommendations or preferable 25(OH)D serum concentrations. Finally, the aim was to assess the suitability of different carriers and associated risks.
We developed a mathematical bottom-up model of 25(OH)D serum concentrations based on data about vitamin D sources of the German population such as sunlight, food and supplements for all federal states taking seasonal and geographical variations into account. We used this model to calculate the optimal fortification levels of different vitamin D carriers in two approaches. First we calculated required fortification levels based on fixed intake recommendations from e.g. the IOM or the DGE and second based on achieving certain 25(OH)D serum concentrations.
To lift 25(OH)D serum concentration in Germany to 75 nmol/L, e.g. 100 g bread has to be fortified with 11.3 μg during winter, resulting in a daily vitamin D intake of 23.7 μg. Bread seems to be a suitable carrier for base supply. However, overdose risk with a single fortified product is higher than the risk with several fortified carriers.
With the model in hand, it is possible to conceive vitamin D fortification strategies for different foodstuffs and model its impact on 25(OH)D serum concentrations.
KeywordsVitamin D Vitamin D deficiency Vitamin D food fortification
Sufficient vitamin D intake as well as adequate vitamin D synthesis in the skin is required to control calcium homeostasis a bone turnover. The effects of vitamin D on human health are diverse  but not yet fully investigated. However, vitamin D has been implicated in the risk of overall mortality , cancer [3–12], diabetes [13–15], musculoskeletal disorders , mental  and physical performance , hypertension , cardiovascular diseases , and autoimmune diseases [19, 21]. Although, many benefits of vitamin D are ubiquitously known, recommended intake (RI) and more importantly upper limits (UL) have to be considered to prevent adverse effects such as vitamin D intoxication. Intoxication may occur at 25(OH)D concentrations above 500 nmol/L , while 75 nmol/L are considered as adequate [23, 24].
In Germany, vitamin D intake from natural food sources [25, 26] as well as vitamin D synthesis in the skin is low , which subsequently leads to low 25(OH)D serum concentrations. In Germany this was once reported in a population study of Hintzpeter and co-workers  and is now detailed with a novel mathematical bottom-up model of 25(OH)D concentrations . Building on this knowledge, the aim of our study was to develop a novel vitamin D fortification model, taking into account all vitamin D sources, different carrier products suitable for fortification and various fortification scenarios to fulfill requirements of risk considerations as well as both intake recommendations and 25-hydroxyvitamin D concentrations.
Earlier fortification models have been published by Flynn and co-workers , Rasmussen and co-workers  or by Hirvonen and co-workers . Models from Flynn and Rasmussen consider the safe upper limit for vitamin D fortification per energy unit. While in the Flynn model only vitamin D intake from natural food sources is considered as the basis for estimating the fortification levels, the Rasmussen model also takes into account the vitamin D intake from supplements. Whereas these two models give fixed values based on equations, the Hirvonen model developed the association between the risk of exceeding the UL and the fortification level. This is important for risk managers in order to decide on the acceptable risk. Our model, however aimed to combine advantages of previous models and add another, yet unconsidered, but significant aspect to vitamin D fortification modeling. It includes not only food intake from natural food sources and supplemental habits, but also vitamin D synthesis in the skin. In order to allow risk considerations, we defined various fortification scenarios for different dietary intake of natural food sources (5th percentile, mean and 95th percentile). Still, we have to mention that our study does not include estimates on an individual level, as it only considers average data.
Model is based on three core dimensions
A bottom-up model of 25(OH)D serum concentrations  as a function of sun exposure, food and supplements predicts and considers both vitamin D sources and vitamin D status of the average population in Germany. Output values are 25(OH)D serum concentrations of an average German individual for each month of the year and for each German federal state. For detailed description of the model and its results please see “New perspectives on vitamin D sources in Germany based on a novel mathematical bottom-up model of 25(OH)D serum concentrations” .
The x-axis – vitamin D intake – represents daily vitamin D intake through natural food sources as well as supplements . While individuals of the 95th (zero point) percentile have high vitamin D intake, individuals of the 5th percentile (furthest from zero point) have low vitamin D intake. The more vitamin D the population consumes on average the less the food has to be fortified.
The y-axis – carrier foodstuff consumption – plots consumption habits of the general population for foodstuffs, which this model considers to be fortified. Zero point of y-axis belongs to the 95th (high carrier intake scenario) percentile of food consumers who consume large quantities of considered fortified carriers and the 5th (low carrier intake scenario) percentile, furthest from zero point, belongs to those who consume very little of respective foodstuff. The average consumption of considered foodstuff in the population is represented by the “mean carrier intake” scenario. As there are differences between men’s and women’s nutritional habits, in all “high carrier intake” and in all “mean carrier intake” case scenarios, higher consumption volumes and thus lower fortification levels were used for reasons of conservative considerations. In all regarded carriers, men are those who consume more than women. Only in the “low carrier intake” scenario, we used consumption quantities of those, who consume less. For all carriers considered this means women. An exemption to this is milk as in the 5th percentile of milk consumers, men consume less than women. The “low carrier intake” (5th percentile) scenario means that 95% of the individuals of the population would have an additional vitamin D intake through fortified food, which lifts their intake and thereby their 25(OH)D serum concentrations to a targeted level (z-axis).
The z-axis – intake recommendation or recommended 25(OH)D level – describes the recommended vitamin D intake or a 25(OH)D serum concentration to achieve. Zero point of z-axis refers to individuals, who tend to meet RI values of the Institute of Medicine (15 μg per day, IOM) and thereby reach 25(OH)D serum concentrations of 50 nmol/L which is defined as the lower value for adequate circulating 25(OH)D level by the IOM . For the UL we considered people older than 8 years with an upper intake limit of 100 μg  or with a serum threshold of 75 nmol/L [23, 24].
Seasonally varying fortification introduced as alternative approach to constant fortification
This model is being developed in two approaches. The first approach aims to define a constant fortification (z-axis as intake recommendation) of different carrier foodstuffs throughout the year, as is common practice. For the constant fortification model, the vitamin D serum concentration model  was only used in parts. That is because 25(OH)D serum levels are not used as calculation base, but only vitamin D intake from natural food sources plus an average vitamin D intake from vitamin D supplements. To calculate constant fortification (fc) levels of carrier foodstuff, the difference (δi) between recommended vitamin D intake (Ir) and actual vitamin D intake through natural food sources and supplements (Ia) is divided by intake of considered food to be fortified (Fi), which are bread and milk as well as juice. This model can be easily adapted to all fortifiable food sources, but we only considered the three mentioned products. The underlying rationale of choosing these foodstuffs was on the one hand the goal to choose a carrier that is consumed by most people in Germany (here bread) and to choose carriers, for which there are many fortification experiences in other countries (here milk as well as juice).
Input parameters of the model
Value or comment
Vitamin D serum concentration model
Varies per month and per federal state of Germany [nmol/L]; average: 45 nmol/L
Brown et al .
Vitamin D intake through food
Varies per gender; mean average men: 3.4 μg and mean average women: 2.8 μg per day
Brown et al .
Carrier foodstuff consumption
National Nutritional Survey II 
46 g/43 g
180 g/134 g
377 g/270 g
National Nutritional Survey II 
16 g/22 g
222 g/203 g
712 g/555 g
National Nutritional Survey II 
0 g/0 g
270 g/232 g
1,200 g/1,000 g
Intake recommendation or 25(OH)D recommendation
Upper Limit (UL)
Recommended 25(OH)D conc.
Bischoff-Ferrari et al.,
Bischoff-Ferrari et al ,
Domarus et al.
Domarus et al .
Conversion factor fortified food to 25(OH)D serum increase
2.32 nmol/L per 1 μg
All models were calculated using Excel version 2007. Macros were programmed in Visual Basic version 6.5. Pictures were created using PowerPoint version 2007 and Think-Cell version 5.2.
This study was approved by the local ethics board of the University Medical Center Hamburg. There was no need for further ethics approval as the study is only based on publicly available data (see Table 1: Input parameters of the model). Hence there were no direct participants in our study which is why no written informed consent for participation in the study needed to be obtained.
Ideal fortification levels vary by underlying conditions
Effects on 25(OH)D concentration serve as basis for risk assessment
We compared the conventional approach of constant food fortification with a new one that takes into account seasonal variations of 25(OH)D concentrations. To our knowledge this is the first model that is able to find a fortification level, which is needed to either lift an average individual of the German population to a certain predefined 25(OH)D serum concentration or to raise the intake of an individual to a recommended intake. For means of risk assessments, this model considers several scenarios to estimate upper, mean and lower fortification levels for individuals with different intake. The novelty of the model in hand is based on the fact that it considers 25(OH)D serum concentrations rather than only intake recommendations and thus aims to level the 25(OH)D level throughout the year. Our model is programmed in a way that it can be easily adapted to all countries and all vitamin D carriers as long as input parameters are available for respective nations. Although the fortification model is based on simple mathematics, some aspects of the method of the model (4.1), the assumptions and input parameter (4.2) as well as the results (4.3) remain up for discussion and have to be further validated.
The method of the model
Our approach is different to previously published models from Rasmussen et al. , Flynn et al.  or Hirvonen et al.  in two ways. First, these models add a specific level of vitamin D per 100 kcal. Our model adds a specific level of vitamin D per 100 g of food, but also considers intake of the German population. Due to the combination of intake in gram and fortification levels in vitamin D per 100 g, the calculation results in a similar logical approach, as our model is likewise able to define fortification levels for people with low, mean or high vitamin D intake. Second, our model not only considers fortification levels to meet certain intake levels, but also takes into account seasonal variations of 25(OH)D levels due to sun exposure. When making risk assessments, the second reason might be considered a shortcoming of our approach, as vitamin D synthesis in the skin may override the effects of nutritional and supplemental intake [35–37]. It could be thus raised to question, whether upper limit considerations are meaningful in the second approach. Opinions are divided concerning the contribution of sunlight as influencing factor for 25(OH)D serum concentrations. Diffey et al.  state that the sun may make up to 56% percent during summer times, while Shariari et al.  report that sun may contribute to vitamin D concentrations by more than 90%. As only average sun exposure habits are available as input parameter for Germany, risk assessment statements in the seasonal variations approach may be put up for debate.
The assumptions and input parameter
Our model is based on a set of input parameter, see Table 1. While some parameters such as recommended intake levels are non-Country specific, some parameters are, e.g. foodstuff consumption. When adapting our model to other countries the availability of these Country specific parameters are a key prerequisite. Nevertheless, data availability might be a challenge in some countries.
We made every effort to refrain from input assumptions wherever possible. Nonetheless, an element of uncertainty remains the conversion factors of fortified food. In our model we used the systematic review of O’Donnell et al.  that determines the effects of vitamin D–fortified foods on serum 25-hydroxyvitamin D 25(OH)D concentrations, because the carrier products assessed in O’Donnell’s study match the vitamin D carrier portfolio chosen in our study. Yet these conversion factors have been subject of various discussions. Other researchers such as Vieth  claim that the conversion factor is lower at around 0.5-1.5 nmol/L per 1 μg vitamin D. However, our model is designed in a way that recalculation based on adapted input parameters, e.g. a lower conversion factor, can easily be performed.
The results of our fortification model (see example calculation in chapter “results”), stating that an average individual needs approximately 23.7 μg a day to reach a concentration of 75 nmol/L, are in line with other observations [7, 11, 24, 39–44]. Other publications are of similar statements, proposing 25 μg to obtain an adequate serum 25(OH)D in the absence of UVB irradiance  or to raise the level by up to 25 nmol/L , which is comparable to our results. However the intake needed per day to reach a concentration of 75 nmol/L remains controversial since other publications suggest required intake levels of 40 μg per day and higher [47, 48]. Furthermore it is important to note that determining fortification levels based on an average individual’s behavior implies that only a certain proportion of the entire population reaches the desired serum concentrations. If the goal is to lift the serum concentration of almost the entire population to a desired level, fortification levels have to be set much higher. However, in this case risk implications gain in importance.
Concerning food products to be fortified, one can argue, whether bread is a suitable carrier for vitamin D as there are only few, but promising experiences [49, 50]. However from a nutritional point of view in Germany, bread makes sense in a couple of dimensions. Bread is a basic and a perishable foodstuff in Germany and it is the only food that does not show a consumption decline in the elderly population , which is of special importance to prevent osteoporosis. All age categories and all social classes consume bread and the difference between mean intake and the 95th percentile is low compared to other potential vitamin D carriers . This makes the amount of vitamin D intake through fortified foodstuff controllable. Additionally, bread is not a peak product such as juice (frequently consumed during some seasons, like summer time) that could potentially boost vitamin D concentrations to a maximum due to increased intake . Hirvonen et al.  also show that bread is an efficient vitamin D carrier when looking for a solution to reduce the proportion of people with low vitamin D intake and which is safe in avoiding the risk of exceeding the UL. Still it remains open, whether vitamin D fortified bread alone can be the solution to alleviate vitamin D deficiency in Germany, as some studies show that food fortification with vitamin D is more efficient when a wide variety of foods are fortified with a low concentration [30, 51]. The risk of overdose is higher for those, who consume larger quantities of certain foods, when only some foodstuff is fortified with high vitamin D concentrations . The more food is fortified with lower concentration, the less likely is overdosing, as nobody can consume high quantities of all foodstuff that is fortified . This is also in line with Välimäki and co-workers . Considering the two other proposed foodstuffs to be fortified, milk as well as juices are common carriers for vitamin D [52–56], which however does not necessarily make these products suitable for fortification in Germany. A reason against milk and juice as carriers is the fact that the quantity spread of consumption for these foodstuffs is rather high . In Finland, for example, this holds true for young women, who are not reached by the current milk fortification policy .
Bottom estimates (5th percentile) in Figure 4B shows almost no difference for milk and juice, as the 5th percentile almost consumes nothing of those carrier products. This does not hold true for bread as even the 5th percentile consumes at least some bread. Top estimate (95th percentile), reflects the quantity spread in consumption habits, especially for milk and juice. This is subsequently reflected in massive 25(OH)D concentration increase. One has to mention that these extreme estimates reflect very unlikely scenarios. However, these estimates are useful for risk considerations as they represent the maximum 25(OH)D concentration increase.
Regardless of the fortification strategy and its potential beneficial impact on the health of the general population, one has to keep in mind two things. First, food fortification per se is not allowed in Germany. There are only few exemptions allowed for general fortification. Among them are margarine, blended fat products as well as dietary food products. Second, vitamin D food fortification poses the risk of a vitamin D intoxication, though it appears to have been caused by excessive vitamin D fortification of dairy milk [58–60]. Furthermore, intoxication is not the only risk, which might go in hand with vitamin D food fortification. Although the therapeutic window for a safe supplementation of vitamin D is extremely wide, some groups could be at risk. The body regulates the biologic activation of cholecalciferol through control of 1α-hydroxylase activity . This, however, does not apply for the safe supplementation of the active hormone (calcitriol) for example for people with chronic kidney disease, as the therapeutic window is relatively small here .
We compared the conventional approach of constant food fortification with a new strategy that takes into account seasonal variations of 25(OH)D concentrations. We managed to show that bread as carrier product may be a suitable base. In terms of risk management, however, bread alone is probably not sufficient, as the risk of overdose with a single fortified product is higher than the risk with several fortified carriers [30, 51]. Our model is programmed in a way that it can be easily adapted to all countries and all vitamin D carriers as long as input parameters are available for respective nations. To our knowledge, our model with its approach is unique and may help many countries, where the population is prone to vitamin D deficiency and which are searching for a strategy to improve the vitamin D status of their population to realize associated benefits . General vitamin D intake and respectively 25(OH)D concentrations of the German population is low. A possible reason might be that food fortification is still prohibited in Germany. With this novel model in hand, it is possible to conceive vitamin D fortification strategies for different foodstuffs and model its impact on 25(OH)D concentrations. We propose to critically discuss the strategy of constant food fortification and show considerations for a seasonal variation of food fortification to balance 25(OH)D concentrations on an certain level.
German nutrition society (Deutsche Gesellschaft für Ernährung)
Institute of Medicine
The authors thank Dr. Scheidt-Nave, Dr. Mensink as well as Dr. Hintzpeter for their helpful comments and critical discussions.
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