there is little doubt that vitamin d deficiency across all age groups in europe is a problem , the magnitude of which ranges from significant to pandemic depending on which biochemical definition one uses ; that is , what level of serum 25-hydroxyvitamin d [ 25(oh)d ; the nutritional status measure for vitamin d ] is used as the cutoff to define deficiency . for example , it is universally accepted that serum 25(oh)d levels should be maintained above an absolute minimum of 25 nmol / l at all times for prevention of osteomalacia in adults and vitamin d - dependent rickets in children ( 1 ) . currently in the uk , about 21% of adolescents ( 2 ) , 25% of adults ( 3 ) , and 35% of older adults in residential care ( 4 ) are clinically vitamin d deficient during wintertime with serum 25(oh)d levels below 25 for example , andersen et al . ( 5 ) in their study of adolescent girls and elderly women in four northern european countries showed that 37% of girls and 17% of women had wintertime serum 25(oh)d below 25 the problem of low vitamin d status spreads from eastern to western and from northern to southern europe ( 57 ) . less severe vitamin d deficiency [ represented by a serum 25(oh)d value < 50 nmol / l , although values between 30 and 110 nmol / l have been suggested ( 810 ) ] causes secondary hyperparathyroidism and increases bone turnover and bone loss ( 11 , 12 ) . in addition to its well - accepted role in these metabolic bone diseases , a large epidemiological , biologically plausible evidence base has increased exponentially during the last decade linking low vitamin d status [ serum 25(oh)d < 50 nmol / l ] with development of non - skeletal diseases ( including the cardiometabolic syndrome , diabetes , selected cancers , respiratory infections , autoimmune and inflammatory diseases , and cognitive decline ) ( 1315 ) , which collectively make a huge contribution to the global burden of disease and total chronic disease deaths . however , it is worth noting that the evidence basis for some of these outcomes awaits data from randomized clinical trials ( rcts ) to prove cause and effect . currently in the uk , about 4055% adolescents ( 2 ) , 7075% of 1964-year - old adults ( 3 ) , and up to 90% of elderly ( 4 ) are vitamin d deficient during wintertime using a serum 25(oh)d cutoff of 50 nmol / l . for example , andersen et al . ( 5 ) in their study of adolescent girls and elderly women in four northern european countries showed that 92% of girls and 67% of women had wintertime serum 25(oh)d below 50 this biochemical cutoff for vitamin d deficiency was accepted recently by the standing committee of european doctors ( 16 ) . some researchers have suggested that serum 25(oh)d levels need to be in excess of 80120 nmol / l to optimize health ( 13 , 14 ) . most european subjects will have serum 25(oh)d levels below this cutoff in winter and a very high proportion will not reach it even in summer ( 3 , 57 ) . in humans , vitamin d is obtained primarily through cutaneous biosynthesis in the presence of ultraviolet blue ( uvb ) sunlight in summer . during wintertime in latitudes greater than 35n , the angle of the sun is too oblique for uvb rays to pass through ozone , so little or no vitamin d is dermally synthesized . the duration of this period during which vitamin d can not be synthesized increases with latitude so , for example , human skin exposed to sunlight on cloudless days in boston ( 42.2n ) from november through february produced no previtamin d3 . in edmonton ( 52n ) this ineffective winter period extended from october through march ( 17 ) . improved adherence to public health campaigns to promote sun safety and awareness of the links between excessive sun exposure and skin cancer , as well as premature wrinkles , has led to the widespread use of sunscreen and inclusion of sun protection factor ( spf ) ingredients in cosmetic products . correct application of sunscreen with an spf of 15 reduces cutaneous skin production of previtamin d3 by 93% ( 18 ) . dermal synthesis of vitamin d is a much less efficient process in non - caucasians than in caucasians and in older than in younger adults . discreet clothing habits limit sun exposure particularly in veiled women and long working hours spent indoors mean that most adults rely on vacation to spend time outdoors during the day . in the absence of sufficient uvb for dermal synthesis , vitamin d becomes an essential nutrient ; however , food sources of vitamin d are few and the typical average vitamin d intakes in populations within the eu are generally around 25 g / d ( 19 ) . there is a significant gap between typical intakes in european populations and the current dietary targets ( 10 and 15 g / d for 170 years ; 10 and 20 g / d for > 70 years ; us estimated average requirement and recommended dietary allowance values , respectively ( 8) ) . even these new dri values are not as high as those proposed by some researchers ( 22 ) . for example , data from nationally representative surveys shows that 74% of adults in the uk and ireland are not reaching an intake of 5 g / d and 90% of older men and women in ireland are not reaching 10 g / d ( 20 , 21 ) . the european dietary recommendation ( pri ) for vitamin d for adults also reveals considerable uncertainty about the available evidence on which to base a recommended intake , as it ranges from 0 to 10 g / d to account not only for the knowledge gaps but also for the widely varying latitudes that eu citizens live in ( 3570n ) , assuming a higher dietary requirement in more northerly latitudes but not having data to base a requirement on ( 23 ) . two recent controlled , randomized , double - blind vitamin d3 intervention trials , the first in 245 adults aged 2040 years ( 24 ) and the second in 225 community - dwelling adults over 64 years ( 25 ) , showed that the estimated dietary requirements ( covering needs of 97.5% of population ) for vitamin d in men and women ( aged 2040 years and 64 + years ) to maintain serum 25(oh)d above 25 nmol / l during winter were 8.6 and 8.7 g / d , respectively . using the 50 nmol / l cutoff , the requirements raised to 24.7 and 28.0 g / d for 2040 and 64-year - olds , respectively . nmol / l in adults and elderly range from 41 to 114 g / d ( 2426 ) . of particular concern , these new target values ( even the lowest ones ) are considerably beyond current intakes in adolescent ( 2 , 27 ) and adult populations ( in some cases even the high consumers ( reflected by those in the 95 percentile of intake ) have vitamin d intakes below 9 g / d ( 19 ) . as an example , 8497% of adolescents ( 2 ) and 93% of adults ( 20 ) in the uk national diet and nutrition survey do not reach an intake of 5 and 9 g / d , respectively . as mentioned already , in humans , vitamin d is obtained primarily through cutaneous biosynthesis in the presence of uvb sunlight in summer . while stores established during summer sun exposure can help reduce the requirement for dietary vitamin d in wintertime in addition , it is worth noting that population levels of unprotected summer sun exposure may be rapidly declining , as a consequence of public education campaigns in relation to skin cancer ( 28 ) . thus , dietary supply of vitamin d is taking on increasing importance not only in winter months but potentially also in summer ; however , dietary supply is low for most european populations . it has been emphasized and re - emphasized that there are only a limited number of public health strategies available to correct low dietary vitamin d intake : 
 improving intake of naturally occurring vitamin d - rich foods . however , this is the least likely strategy to counteract low dietary vitamin d intake due to the fact that there are very few food sources that are rich in vitamin d. furthermore , most of these are not frequently consumed by many in the population ( 21).vitamin d fortification ( mandatory or voluntarily ) of food . this has been viewed by some as a feasible and effective measure once applied in an evidence - based approach . in response to concerns about widespread vitamin d deficiency , fortification of foods with vitamin d in the us and canada has an important impact on the mean daily intake of vitamin d by the average adult . fortified foods constitute the largest contributor ( 6587% ; and fortified milk alone contributes 4064% ) to dietary vitamin d intake in the us population ( 29 ) . however , calvo and whiting ( 30 ) suggest that the current level of fortification in the us and canada is not effective in reaching the required levels of vitamin d intake ( i.e. existing dietary targets , which are much lower than those shown by the recent rcts described above ) . this may relate to the level of fortification , types and choice of food vehicles , and the issue of mandatory or optional / voluntary fortification . o'donnell et al . ( 31 ) , in their recent systematic review of the efficacy of food fortification on serum 25(oh)d concentrations , showed that of the nine rcts ( n=889 subjects , all community - dwelling participants ; most used dairy products as the source of vitamin d fortification ) that were included , eight consistently showed a significant beneficial effect of food fortification on 25(oh)d concentrations . the authors concluded that their review highlights the need for stronger data on food fortification . flynn et al . ( 19 ) have recently shown that the 95th percentile of intake of vitamin d from voluntary fortified foods in europe is low . thus , from a european perspective we need to model european food and vitamin d intake data to ascertain which food vehicles and what level of vitamin d addition will ensure an effective but safe rise in serum vitamin d status in european populations . supplementation with vitamin d has been shown to significantly improve vitamin d intake across a variety of age , race , ethnic , and gender groups ( 30 ) as well as improving vitamin d status per se ( efficacy of which dependent on dose ) ( 32 ) . however , evidence seems to suggest that the population intake of vitamin d from supplements is quite low ( 19 ) . for example , although supplements contribute 12 and 7% to vitamin d intakes in irish women and men , respectively ( 33 ) and almost a quarter of vitamin d intakes in women and 12% in men in the uk ( 20 ) , overall intakes are low so these contributions while proportionally high are quantitatively low . this is a function mainly of the relatively low vitamin d content of most supplements in some countries relative to requirement as discussed above . some are of the view that while not highly effective at a population level , vitamin d supplementation may be appropriate in high risk groups such as the elderly ( 16 , 34 , 35 ) . improving intake of naturally occurring vitamin d - rich foods . however , this is the least likely strategy to counteract low dietary vitamin d intake due to the fact that there are very few food sources that are rich in vitamin d. furthermore , most of these are not frequently consumed by many in the population ( 21 ) . this has been viewed by some as a feasible and effective measure once applied in an evidence - based approach . in response to concerns about widespread vitamin d deficiency , fortification of foods with vitamin d in the us and canada has an important impact on the mean daily intake of vitamin d by the average adult . fortified foods constitute the largest contributor ( 6587% ; and fortified milk alone contributes 4064% ) to dietary vitamin d intake in the us population ( 29 ) . however , calvo and whiting ( 30 ) suggest that the current level of fortification in the us and canada is not effective in reaching the required levels of vitamin d intake ( i.e. existing dietary targets , which are much lower than those shown by the recent rcts described above ) . this may relate to the level of fortification , types and choice of food vehicles , and the issue of mandatory or optional / voluntary fortification . 31 ) , in their recent systematic review of the efficacy of food fortification on serum 25(oh)d concentrations , showed that of the nine rcts ( n=889 subjects , all community - dwelling participants ; most used dairy products as the source of vitamin d fortification ) that were included , eight consistently showed a significant beneficial effect of food fortification on 25(oh)d concentrations . the authors concluded that their review highlights the need for stronger data on food fortification . 19 ) have recently shown that the 95th percentile of intake of vitamin d from voluntary fortified foods in europe is low . thus , from a european perspective we need to model european food and vitamin d intake data to ascertain which food vehicles and what level of vitamin d addition will ensure an effective but safe rise in serum vitamin d status in european populations . so there is a need to invest in such research . supplementation with vitamin d has been shown to significantly improve vitamin d intake across a variety of age , race , ethnic , and gender groups ( 30 ) as well as improving vitamin d status per se ( efficacy of which dependent on dose ) ( 32 ) . however , evidence seems to suggest that the population intake of vitamin d from supplements is quite low ( 19 ) . for example , although supplements contribute 12 and 7% to vitamin d intakes in irish women and men , respectively ( 33 ) and almost a quarter of vitamin d intakes in women and 12% in men in the uk ( 20 ) , overall intakes are low so these contributions while proportionally high are quantitatively low . this is a function mainly of the relatively low vitamin d content of most supplements in some countries relative to requirement as discussed above . some are of the view that while not highly effective at a population level , vitamin d supplementation may be appropriate in high risk groups such as the elderly ( 16 , 34 , 35 ) . while recent evidence suggests that the levels of vitamin d added to food and/or supplements would need to be high so as to ensure dietary requirements are met and health outcomes optimized , knowledge of which are the most effective forms of vitamin d to use in some of these preventative approaches is also important . while vitamin d2 and d3 [ the two main food derived forms ( although vitamin d2 only occurs in wild mushrooms ) and those used in vitamin d supplements ] both unquestionably elevate serum 25(oh)d as evidenced in a recent systematic review of biomarkers of vitamin d status ( 32 ) , there is still uncertainty in relation to the relative efficacy of these two forms of vitamin d. for several decades , pharmacopoeias have officially regarded these two forms as equivalent and interchangeable , yet the evidence base for this was old and largely based on studies of rickets prevention in infants in the 1930s . there have been a number of human studies that directly compared the two forms of vitamin d in terms of their potential for raising serum 25(oh)d in adults . trang et al . ( 36 ) compared the ability of an equal molar dose of vitamin d2 or d3 [ 4,000 iu ( 100 g)/d ] to elevate serum total 25(oh)d ( via radioimmunoassay ) over 2 weeks between february and early may when vitamin d concentrations and solar exposure are minimal in 72 healthy men and women ( mean age , 38 years ) . both vitamin d2 and vitamin d3 increased serum total 25(oh)d concentrations , but the increase in total 25(oh)d was found to be 70% greater ( 1.7 times ) with vitamin d3 than the increase obtained with vitamin d2 . ( 37 ) compared the time course of serum total 25(oh)d ( via radioimmunoassays ) over a period of 28 days after a single dose of either vitamin d2 or vitamin d3 [ 50,000 iu ( 1250 g ) ] in 20 healthy males ( mean age , 33.0 years ) in summertime ( july ) [ necessitating the researchers having to account and adjust for increases in serum 25(oh)d due to sun exposure ] . both forms of vitamin d produced similar rises in serum total 25(oh)d concentration over the first 3 d , but serum 25(oh)d continued to rise in the vitamin d3-treated subjects ( peaking by day 14 and remaining above baseline until at least day 28 ) , whereas in the vitamin d2-treated subjects , serum 25(oh)d concentrations fell rapidly , reaching baseline values by day 14 . interestingly , 25(oh)d concentrations then continued to decline in this group and fell below baseline values by day 28 . a comparison of the areas under the curve ( concentration versus time ) showed a > threefold greater potency with vitamin d3 . a surprising finding was a decline in 25(oh)d3 concentrations ( via hplc assay ) in the vitamin d2-treated subjects , whereas concentrations rose in the control group ( due to sun exposure ) ( 37 ) . ( 38 ) studied whether 1,000 iu ( 25 g)/d of vitamin d2 and d3 are equipotent therapies in vitamin d - insufficient [ serum 25(oh)d < 50 vitamin d3 supplementation resulted in a 31% greater increase in total hplc - measured 25(oh)d and 52% greater rise in radioimmunoassay - measured total 25(oh)d than supplementation with an equivalent dose of vitamin d2 after 3 months . the authors also reported a lack of difference in pth lowering between the two forms of vitamin d treatments and raised questions about the biological importance of the greater potency with vitamin d3 . houghton and vieth ( 39 ) , in their review of the available data and evidence , provide a very succinct overview of several biologically plausible mechanisms that could contribute to the greater capacity of vitamin d3 over d2 to maintain higher 25(oh)d concentrations over time , including : 
 serum 25(oh)d2 has a lower affinity for vitamin d - binding protein ( dbp ) and results in a shorter circulating half - life than that of 25(oh)d3.a higher affinity of hepatic 25-hydroxylase for vitamin d3 than for vitamin d2.minor differences in the chemistry of side chains between the two forms of vitamin d result in differences in the site of hydroxylation and leads to the production of unique biologically active metabolites : after 25-hydroxylation , 25(oh)d , and 1,25(oh)2d undergo additional 24-hydroxylation in the kidney to form 24,25(oh)2d and 1,24,25(oh)3d , respectively.the formation of 1,24,25(oh)3d2 leads to deactivation of the vitamin d2 molecule , whereas the analogous vitamin d3 metabolite , 1,24,25(oh)3d3 , must undergo additional side - chain oxidation to be biologically deactivated . 1,24,25(oh)3d3 has the ability to bind to the vitamin d receptor [ vdr ; 40% more than 1,25(oh)2d3 ] and , thus , is able to potentially generate significant biological activity.while 24-hydroxylation of the side chain could occur only after 25-hydroxylation , at least for vitamin d3 , it does not appear to be a prerequisite for vitamin d2 . 1,24(oh)2d2 , formed in the kidney from 24(oh)d2 , has less affinity for vdr than do 1,25(oh)2d3 and 1,24(oh)2d3 . binding to vdr represents a molecular event important to the biological action of the vitamin d metabolites . the authors concluded that when the data and findings are taken together , the most plausible explanations for the greater bioefficacy of vitamin d3 are conceivably due to the higher affinities of vitamin d3 and its metabolites than vitamin d2 for hepatic 25-hydroxylase , dbp , and vdr and because vitamin d3 is not directly metabolized to 24(oh)d as is vitamin d2 . interested readers are referred to this review for a more comprehensive coverage of the potential mechanisms ( 39 ) . serum 25(oh)d2 has a lower affinity for vitamin d - binding protein ( dbp ) and results in a shorter circulating half - life than that of 25(oh)d3 . a higher affinity of hepatic 25-hydroxylase for vitamin d3 than for vitamin d2 . minor differences in the chemistry of side chains between the two forms of vitamin d result in differences in the site of hydroxylation and leads to the production of unique biologically active metabolites : after 25-hydroxylation , 25(oh)d , and 1,25(oh)2d undergo additional 24-hydroxylation in the kidney to form 24,25(oh)2d and 1,24,25(oh)3d , respectively . the formation of 1,24,25(oh)3d2 leads to deactivation of the vitamin d2 molecule , whereas the analogous vitamin d3 metabolite , 1,24,25(oh)3d3 , must undergo additional side - chain oxidation to be biologically deactivated . 1,24,25(oh)3d3 has the ability to bind to the vitamin d receptor [ vdr ; 40% more than 1,25(oh)2d3 ] and , thus , is able to potentially generate significant biological activity . while 24-hydroxylation of the side chain could occur only after 25-hydroxylation , at least for vitamin d3 , it does not appear to be a prerequisite for vitamin d2 . 1,24(oh)2d2 , formed in the kidney from 24(oh)d2 , has less affinity for vdr than do 1,25(oh)2d3 and 1,24(oh)2d3 . binding to vdr represents a molecular event important to the biological action of the vitamin d metabolites . while the findings from the above studies and possible underlying mechanisms might suggest so , the case for greater bioefficacy of vitamin d3 over vitamin d2 is less than clear . ( 40 ) reported that in a study of elderly women ( mean age , 72 years ) who self - reported their use of vitamin d2 and d3 supplements , the mean serum total 25(oh)d levels ( via competitive protein binding assay ) were higher in women on vitamin d2 ( 33.62.1 ng / ml ) and vitamin d3 ( 29.71.8 ng / ml ) supplements ( mean dose , 401 and 465 iu / d , respectively ) compared to unsupplemented women ( 27.30.7 ng / ml ) during wintertime . ( 41 ) showed that elevations in serum total 25(oh)d concentrations ( via liquid chromatography tandem mass spectroscopy ) were identical between healthy adult men and women ( n=68 ; mean age , 38.6 years ) given 1,000 iu ( 25 g)/d vitamin d2 or vitamin d3 or a combination of 500 iu / d of vitamin d2 plus 500 iu / d of vitamin d3 ( 1,000 iu / d in total ) in capsule form at the end of the winter for 3 months . furthermore , the 25(oh)d3 levels did not change in the group that received 1,000 iu vitamin d2 daily . similarly , infants ( mean age , 10 months ) who received 2,000 iu ( 50 g ) daily or 50,000 iu ( 2,000 g ) vitamin d2 weekly for 6 weeks ( throughout the year ) experienced an elevation in serum total 25(oh)d concentrations ( via a chemiluminescent assay ) equivalent to concentrations observed in children who received 2,000 iu vitamin d3 daily ( 42 ) . ( 43 ) very recently showed in a study of healthy adult men and women ( n=105 ; mean age , 40.3 years ) in late winter that , using analysis of the area under the curve , there was no significant difference in serum total 25(oh)d ( via liquid chromatography tandem mass spectroscopy ) between subjects who consumed vitamin d3-fortified orange juice and vitamin d3 capsules . similarly , no significant difference in serum 25(oh)d2 was observed between subjects who consumed vitamin d2-fortified orange juice and vitamin d2 capsules . in addition , there was no significant difference in serum total 25(oh)d between subjects who consumed 1,000 vitamin d2 or d3 in orange juice or in a capsule . thus , these latest findings appear to suggest that not only are vitamin d2 and vitamin d3 equally bioavailable , they are so from a fortified food source or a capsule . it is clear that the data are ambiguous and may stem from the fact that the various studies that have compared the two forms of vitamin d have had differences in design ( season in which study conducted , age profile of subjects ) , dose / mode of administration of vitamin d , preparation of vitamin d , as well as method of analysis of serum 25(oh)d , all of which may have contributed to the mixed findings and limit a firm conclusion being drawn at this time . the major metabolite of vitamin d with biological activity is 1,25(oh)2d ; however , this is usually used for pharmacological purposes and is not typically used in normal healthy people . the presence of minor amounts of this metabolite in some foods of animal origin ( as is the case with 25(oh)d ; see below ) and its contribution to biological vitamin d activity has not been investigated . it has been suggested that the other major metabolite , 25(oh)d , which has also been used for pharmacological purposes , may contribute to vitamin d nutriture . meat , eggs , and to a lesser extent fish have been shown to possess 25(oh)d ( 4447 ) . there has been some limited investigation of offal ( and in particular liver and kidney ) , which shows that they contain higher amounts of the metabolite than cuts of meat ( which is not surprising as these tissues are where vitamin d is metabolized in vivo ) ( 48 , 49 ) . for example , pork liver appears to have equivalent amounts of vitamin d3 and 25(oh)d ( 0.4 g per 100 g ) , while beef liver has more 25(oh)d than vitamin d3 [ < 0.05 g and 0.3 g 25(oh)d per 100 g , respectively ] ( 45 ) . chicken also appears to have equivalent amounts of vitamin d3 and 25(oh)d ( 0.3 g and 0.25 g per 100 g , respectively ) ( 45 ) , while eggs yolk have 3 g vitamin d3 and 1 g 25(oh)d per 100 g , respectively ( 44 ) . meat and meat products as well as egg and egg dishes can make sizeable contributions to the mean daily intake of vitamin d for some populations ( 20 , 21 ) . however , some of this contribution stems from the fact that the uk ( and others such as danish and swiss ) food composition tables suggests that 25(oh)d may possess up to five times the activity of native vitamin d3 in food ( 5052 ) . thus , in theory , each g of 25(oh)d consumed in the diet could boost vitamin d status up to five times more effectively compared to each g of native vitamin d3 in food . thus , food - based 25(oh)d may be a very valuable strategy for bridging the gap between current intakes and new dietary targets for vitamin d ( 910 or 15 g / d ; 8 , 24 , 25 ) ( 24 , 25 ) . for example , if habitual daily intakes of vitamin d in most european populations are in the region of 4 g ( 19 ) , then an additional 5 g / d of vitamin d would need to be achieved via diet to reach a target of 9 g / d or potentially only an additional 1 g / d 25(oh)d from food . this would only be the case if the relative potency of 25(oh)d to the native vitamin d is 5 , but as ovesen et al . ( 48 ) point out there is as yet no consensus on the conversion factor that should be used for 25(oh)d to calculate vitamin d activity . depending on the testing system used , the factor varies from 1.5 to 5 ( 48 ) . moreover , jakobsen et al . ( 53 ) recently showed in a 12-week pig feeding trial that in relation to benefits for human nutrition , 25(oh)d in pig feed should be regarded as lower than vitamin d3 , as meat and liver produced by feeding the pigs exclusively 25(oh)d had a significantly low content of vitamin d3 . priority needs to be given to data from human studies that have experimentally examined this relative potency . using data from a 1-year intervention study by rossini et al . ( 54 ) in osteopenic / osteoporotic women with hypovitaminosis d , it can be estimated that vitamin d3 and 25(oh)d may have about equal potency ( with the latter being only 1.4-fold more potent than vitamin d3 ) . ( 55 ) recently showed that healthy postmenopausal women ( aged 5075 years ) who were supplemented daily with 20 g / d of 25(oh)d had more than a twofold greater increase in serum 25(oh)d after 16 weeks compared to those who were supplemented with 20 g / d of vitamin d3 over the same time frame . clearly , further research is needed to better define the relative potency of 25(oh)d present in foods so that food compositional tables can better reflect the true vitamin d nutritive value of meats , fish , and eggs , but also in terms of whether this metabolite is something that could be used for dietary supplementation / fortification purposes . while vitamin d2 and d3 [ the two main food derived forms ( although vitamin d2 only occurs in wild mushrooms ) and those used in vitamin d supplements ] both unquestionably elevate serum 25(oh)d as evidenced in a recent systematic review of biomarkers of vitamin d status ( 32 ) , there is still uncertainty in relation to the relative efficacy of these two forms of vitamin d. for several decades , pharmacopoeias have officially regarded these two forms as equivalent and interchangeable , yet the evidence base for this was old and largely based on studies of rickets prevention in infants in the 1930s . there have been a number of human studies that directly compared the two forms of vitamin d in terms of their potential for raising serum 25(oh)d in adults . trang et al . ( 36 ) compared the ability of an equal molar dose of vitamin d2 or d3 [ 4,000 iu ( 100 g)/d ] to elevate serum total 25(oh)d ( via radioimmunoassay ) over 2 weeks between february and early may when vitamin d concentrations and solar exposure are minimal in 72 healthy men and women ( mean age , 38 years ) . both vitamin d2 and vitamin d3 increased serum total 25(oh)d concentrations , but the increase in total 25(oh)d was found to be 70% greater ( 1.7 times ) with vitamin d3 than the increase obtained with vitamin d2 . ( 37 ) compared the time course of serum total 25(oh)d ( via radioimmunoassays ) over a period of 28 days after a single dose of either vitamin d2 or vitamin d3 [ 50,000 iu ( 1250 g ) ] in 20 healthy males ( mean age , 33.0 years ) in summertime ( july ) [ necessitating the researchers having to account and adjust for increases in serum 25(oh)d due to sun exposure ] . both forms of vitamin d produced similar rises in serum total 25(oh)d concentration over the first 3 d , but serum 25(oh)d continued to rise in the vitamin d3-treated subjects ( peaking by day 14 and remaining above baseline until at least day 28 ) , whereas in the vitamin d2-treated subjects , serum 25(oh)d concentrations fell rapidly , reaching baseline values by day 14 . interestingly , 25(oh)d concentrations then continued to decline in this group and fell below baseline values by day 28 . a comparison of the areas under the curve ( concentration versus time ) showed a > threefold greater potency with vitamin d3 . a surprising finding was a decline in 25(oh)d3 concentrations ( via hplc assay ) in the vitamin d2-treated subjects , whereas concentrations rose in the control group ( due to sun exposure ) ( 37 ) . ( 38 ) studied whether 1,000 iu ( 25 g)/d of vitamin d2 and d3 are equipotent therapies in vitamin d - insufficient [ serum 25(oh)d < 50 vitamin d3 supplementation resulted in a 31% greater increase in total hplc - measured 25(oh)d and 52% greater rise in radioimmunoassay - measured total 25(oh)d than supplementation with an equivalent dose of vitamin d2 after 3 months . the authors also reported a lack of difference in pth lowering between the two forms of vitamin d treatments and raised questions about the biological importance of the greater potency with vitamin d3 . houghton and vieth ( 39 ) , in their review of the available data and evidence , provide a very succinct overview of several biologically plausible mechanisms that could contribute to the greater capacity of vitamin d3 over d2 to maintain higher 25(oh)d concentrations over time , including : 
 serum 25(oh)d2 has a lower affinity for vitamin d - binding protein ( dbp ) and results in a shorter circulating half - life than that of 25(oh)d3.a higher affinity of hepatic 25-hydroxylase for vitamin d3 than for vitamin d2.minor differences in the chemistry of side chains between the two forms of vitamin d result in differences in the site of hydroxylation and leads to the production of unique biologically active metabolites : after 25-hydroxylation , 25(oh)d , and 1,25(oh)2d undergo additional 24-hydroxylation in the kidney to form 24,25(oh)2d and 1,24,25(oh)3d , respectively.the formation of 1,24,25(oh)3d2 leads to deactivation of the vitamin d2 molecule , whereas the analogous vitamin d3 metabolite , 1,24,25(oh)3d3 , must undergo additional side - chain oxidation to be biologically deactivated . 1,24,25(oh)3d3 has the ability to bind to the vitamin d receptor [ vdr ; 40% more than 1,25(oh)2d3 ] and , thus , is able to potentially generate significant biological activity.while 24-hydroxylation of the side chain could occur only after 25-hydroxylation , at least for vitamin d3 , it does not appear to be a prerequisite for vitamin d2 . 1,24(oh)2d2 , formed in the kidney from 24(oh)d2 , has less affinity for vdr than do 1,25(oh)2d3 and 1,24(oh)2d3 . binding to vdr represents a molecular event important to the biological action of the vitamin d metabolites . the authors concluded that when the data and findings are taken together , the most plausible explanations for the greater bioefficacy of vitamin d3 are conceivably due to the higher affinities of vitamin d3 and its metabolites than vitamin d2 for hepatic 25-hydroxylase , dbp , and vdr and because vitamin d3 is not directly metabolized to 24(oh)d as is vitamin d2 . interested readers are referred to this review for a more comprehensive coverage of the potential mechanisms ( 39 ) . serum 25(oh)d2 has a lower affinity for vitamin d - binding protein ( dbp ) and results in a shorter circulating half - life than that of 25(oh)d3 . a higher affinity of hepatic 25-hydroxylase for vitamin d3 than for vitamin d2 . minor differences in the chemistry of side chains between the two forms of vitamin d result in differences in the site of hydroxylation and leads to the production of unique biologically active metabolites : after 25-hydroxylation , 25(oh)d , and 1,25(oh)2d undergo additional 24-hydroxylation in the kidney to form 24,25(oh)2d and 1,24,25(oh)3d , respectively . the formation of 1,24,25(oh)3d2 leads to deactivation of the vitamin d2 molecule , whereas the analogous vitamin d3 metabolite , 1,24,25(oh)3d3 , must undergo additional side - chain oxidation to be biologically deactivated . 1,24,25(oh)3d3 has the ability to bind to the vitamin d receptor [ vdr ; 40% more than 1,25(oh)2d3 ] and , thus , is able to potentially generate significant biological activity . while 24-hydroxylation of the side chain could occur only after 25-hydroxylation , at least for vitamin d3 , it does not appear to be a prerequisite for vitamin d2 . 1,24(oh)2d2 , formed in the kidney from 24(oh)d2 , has less affinity for vdr than do 1,25(oh)2d3 and 1,24(oh)2d3 . binding to vdr represents a molecular event important to the biological action of the vitamin d metabolites . while the findings from the above studies and possible underlying mechanisms might suggest so , the case for greater bioefficacy of vitamin d3 over vitamin d2 is less than clear . ( 40 ) reported that in a study of elderly women ( mean age , 72 years ) who self - reported their use of vitamin d2 and d3 supplements , the mean serum total 25(oh)d levels ( via competitive protein binding assay ) were higher in women on vitamin d2 ( 33.62.1 ng / ml ) and vitamin d3 ( 29.71.8 ng / ml ) supplements ( mean dose , 401 and 465 iu / d , respectively ) compared to unsupplemented women ( 27.30.7 ng / ml ) during wintertime . ( 41 ) showed that elevations in serum total 25(oh)d concentrations ( via liquid chromatography tandem mass spectroscopy ) were identical between healthy adult men and women ( n=68 ; mean age , 38.6 years ) given 1,000 iu ( 25 g)/d vitamin d2 or vitamin d3 or a combination of 500 iu / d of vitamin d2 plus 500 iu / d of vitamin d3 ( 1,000 iu / d in total ) in capsule form at the end of the winter for 3 months . furthermore , the 25(oh)d3 levels did not change in the group that received 1,000 iu vitamin d2 daily . similarly , infants ( mean age , 10 months ) who received 2,000 iu ( 50 g ) daily or 50,000 iu ( 2,000 g ) vitamin d2 weekly for 6 weeks ( throughout the year ) experienced an elevation in serum total 25(oh)d concentrations ( via a chemiluminescent assay ) equivalent to concentrations observed in children who received 2,000 iu vitamin d3 daily ( 42 ) . ( 43 ) very recently showed in a study of healthy adult men and women ( n=105 ; mean age , 40.3 years ) in late winter that , using analysis of the area under the curve , there was no significant difference in serum total 25(oh)d ( via liquid chromatography tandem mass spectroscopy ) between subjects who consumed vitamin d3-fortified orange juice and vitamin d3 capsules . similarly , no significant difference in serum 25(oh)d2 was observed between subjects who consumed vitamin d2-fortified orange juice and vitamin d2 capsules . in addition , there was no significant difference in serum total 25(oh)d between subjects who consumed 1,000 vitamin d2 or d3 in orange juice or in a capsule . thus , these latest findings appear to suggest that not only are vitamin d2 and vitamin d3 equally bioavailable , they are so from a fortified food source or a capsule . it is clear that the data are ambiguous and may stem from the fact that the various studies that have compared the two forms of vitamin d have had differences in design ( season in which study conducted , age profile of subjects ) , dose / mode of administration of vitamin d , preparation of vitamin d , as well as method of analysis of serum 25(oh)d , all of which may have contributed to the mixed findings and limit a firm conclusion being drawn at this time . the major metabolite of vitamin d with biological activity is 1,25(oh)2d ; however , this is usually used for pharmacological purposes and is not typically used in normal healthy people . the presence of minor amounts of this metabolite in some foods of animal origin ( as is the case with 25(oh)d ; see below ) and its contribution to biological vitamin d activity has not been investigated . it has been suggested that the other major metabolite , 25(oh)d , which has also been used for pharmacological purposes , may contribute to vitamin d nutriture . meat , eggs , and to a lesser extent fish have been shown to possess 25(oh)d ( 4447 ) . there has been some limited investigation of offal ( and in particular liver and kidney ) , which shows that they contain higher amounts of the metabolite than cuts of meat ( which is not surprising as these tissues are where vitamin d is metabolized in vivo ) ( 48 , 49 ) . for example , pork liver appears to have equivalent amounts of vitamin d3 and 25(oh)d ( 0.4 g per 100 g ) , while beef liver has more 25(oh)d than vitamin d3 [ < 0.05 g and 0.3 g 25(oh)d per 100 g , respectively ] ( 45 ) . chicken also appears to have equivalent amounts of vitamin d3 and 25(oh)d ( 0.3 g and 0.25 g per 100 g , respectively ) ( 45 ) , while eggs yolk have 3 g vitamin d3 and 1 g 25(oh)d per 100 g , respectively ( 44 ) . meat and meat products as well as egg and egg dishes can make sizeable contributions to the mean daily intake of vitamin d for some populations ( 20 , 21 ) . however , some of this contribution stems from the fact that the uk ( and others such as danish and swiss ) food composition tables suggests that 25(oh)d may possess up to five times the activity of native vitamin d3 in food ( 5052 ) . thus , in theory , each g of 25(oh)d consumed in the diet could boost vitamin d status up to five times more effectively compared to each g of native vitamin d3 in food . thus , food - based 25(oh)d may be a very valuable strategy for bridging the gap between current intakes and new dietary targets for vitamin d ( 910 or 15 g / d ; 8 , 24 , 25 ) ( 24 , 25 ) . for example , if habitual daily intakes of vitamin d in most european populations are in the region of 4 g ( 19 ) , then an additional 5 g / d of vitamin d would need to be achieved via diet to reach a target of 9 g / d or potentially only an additional 1 g / d 25(oh)d from food . this would only be the case if the relative potency of 25(oh)d to the native vitamin d is 5 , but as ovesen et al . ( 48 ) point out there is as yet no consensus on the conversion factor that should be used for 25(oh)d to calculate vitamin d activity . depending on the testing system used , the factor varies from 1.5 to 5 ( 48 ) . moreover , jakobsen et al . ( 53 ) recently showed in a 12-week pig feeding trial that in relation to benefits for human nutrition , 25(oh)d in pig feed should be regarded as lower than vitamin d3 , as meat and liver produced by feeding the pigs exclusively 25(oh)d had a significantly low content of vitamin d3 . priority needs to be given to data from human studies that have experimentally examined this relative potency . using data from a 1-year intervention study by rossini et al . ( 54 ) in osteopenic / osteoporotic women with hypovitaminosis d , it can be estimated that vitamin d3 and 25(oh)d may have about equal potency ( with the latter being only 1.4-fold more potent than vitamin d3 ) . in contrast , in a preliminary publication , jetter et al . ( 55 ) recently showed that healthy postmenopausal women ( aged 5075 years ) who were supplemented daily with 20 g / d of 25(oh)d had more than a twofold greater increase in serum 25(oh)d after 16 weeks compared to those who were supplemented with 20 g / d of vitamin d3 over the same time frame . clearly , further research is needed to better define the relative potency of 25(oh)d present in foods so that food compositional tables can better reflect the true vitamin d nutritive value of meats , fish , and eggs , but also in terms of whether this metabolite is something that could be used for dietary supplementation / fortification purposes . without question there is a need to address the shortfall in current intakes of vitamin d in european and other populations relative to existing and potentially new and higher dietary recommendations . fortification of foods with vitamin d as well as vitamin d supplementation in specific at - risk groups would appear to be likely strategies that may address low vitamin d status at a population level . further research is needed to clarify whether differences in potency of vitamin d2 and d3 really do exist and to ascertain the exact relative potency of 25(oh)d to vitamin d3 . the author has not received any funding or benefits from industry or elsewhere to conduct this study .
there is little doubt that vitamin d deficiency across all age groups in europe is a problem . 
 low vitamin d status arises due to limited , if any , dermal synthesis during the winter months at latitudes above 40n , putting increased importance on dietary supply of the vitamin 
 . however , dietary intakes by most populations are low due to the limited supply of vitamin d - rich foods in the food chain . 
 thus strategies that effectively address this public health issue are urgently required . 
 it has been emphasized and re - emphasized that there are only a limited number of public health strategies available to correct low dietary vitamin d intake : ( 1 ) improving intake of naturally occurring vitamin d - rich foods , ( 2 ) vitamin d fortification ( mandatory or voluntarily ) of food , and ( 3 ) vitamin d supplementation . 
 recent evidence suggests that the levels of vitamin d added to food would need to be high so as to ensure dietary requirements are met and health outcomes optimized . 
 in addition , knowledge of the most effective forms of vitamin d to use in some of these preventative approaches is important . there is still uncertainty in relation to the relative efficacy of vitamin d2 versus d3 , the two main food derived forms and those used in vitamin d supplements . 
 the major metabolite of vitamin d with biological activity is 1,25(oh)2d ; however , this is usually used for pharmacological purposes and is not typically used in normal , healthy people . 
 the other major metabolite , 25(oh)d , which has also been used for pharmacological purposes is present in certain foods such as meat and meat products ( particularly offal ) as well as eggs . 
 this metabolite may have the potential to boost vitamin d status up to five times more effectively that native vitamin d3 in foods . 
 however , the exact bioactivity of this compound needs to be established .