“ vitamin d ” means either vitamin d3 ( cholecalciferol ) and / or vitamin d2 ( ergocaciferol ). humans are unable to make vitamin d2 ( ergocalciferol ), but are able to use it as a source of vitamin d . vitamin d2 can be synthesized by various plants and is often used in vitamin d in supplements as an equivalent to vitamin d . “ vitamin d metabolite ” means any metabolite of vitamin d other than 25 - hydroxy vitamin d3 . “ 25 - oh d ” refers to the 25 - hydroxylated metabolite of either vitamin d2 or vitamin d3 which is the major circulating form found in plasma . “ prevent ” is meant to include amelioration of the disease , lessening of the severity of the symptoms , early intervention , and lengthening the duration of onset of the disease , and is not intended to be limited to a situation where the patient is no longer able to contract the disease nor experience any symptoms . eotaxins ( also called ccl - 11 , ccl - 24 , and ccl - 26 ) are three proteins which belong to the cc family of chemokines . they are selective recruiters of eosinophils , and also induce the aggregation of eosinophils . eosinophils play an important beneficial role in killing some invasive microbes and helminths , especially in the gut . recent studies also suggest a role in organogenesis , tissue repair , and immune regulation . however , abnormally high amounts of eosinophils in the circulation and in some tissues are characteristic of many pathologies , including allergic diseases ( including asthma , rhinitis , and atopic dematitis ), other inflammatory disorders ( including inflammatory bowel disease , eosinophilic gastroenteritis , and pneumonia ), non - allergenic inflammation ( such as that induced by ozone inhalation or foreign body granlomatous reactions ) as well as some malignancies ( such as hodgkin &# 39 ; s disease and various leukemias ). it has been surprisingly found that administration of 25 - oh d3 lowered the level of eotaxin in the serum of postmenopausal women . the group receiving 25 - oh d3 had a statistically significant lower amount compared to the group receiving vitamin d3 . both 25 - hydroxy vitamin d3 and vitamin d3 lowered eotaxin amounts compared to placebo . thus , administration of 25 - oh d3 would be beneficial for treatment and prevention of diseases and symptoms associated with high levels of eotaxin , as detailed below . as explained in pease et al , 2001 curr . opinion in pharmacol . 1 ( 3 ): 248 - 253 , which is hereby incorporated by reference , one of the characteristic features of asthma is the accumulation of eosinophils in the bronchial walls . when the eosinophils release their contents ( including major basic protein ), tissue damage and bronchial hyperreactivity , the hallmark of asthma , occur . individuals diagnosed with asthma have been found to have an increased eotaxin level , and those experiencing acute asthma have been reported to have higher levels than those with stable asthma . similarly , individuals having occupational asthma were also seen to have higher eotaxin levels . in mice models , a disruption of the eotaxin gene resulted in a reduction of eosinophil recrutiment in an asthma mode . similarly , administration of an eotaxin - neutralizing antibody also was found to reduce lung esophilila . thus another aspect of this invention is a method to decrease the symptoms of asthma by administering a eotaxin - reducing effective amount of 25 - oh d3 to a person in need of such reduction . the resulting reduction of eosinophil aggregation would lead to an observable reduction in symptoms of asthma , notably the easing of bronchial restriction . another aspect of this invention is the use of 25 - oh d3 in the method of making an asthma medicament . the 25 - oh d3 may be used as an adjunct to or in co - therapy with known asthma medicaments and / or therapies . eotaxin was found to be present in epithelial and inflammatory cells in nasal passages of individuals with allergic rhinitis and sinusitis . ( see fiest et al 2006 j allergy clin immunol 118 : 536 - 8 , which is hereby incorporated by reference ). thus eotaxin is a target for reduction in these conditions . atopic asthma refers to allergic conditions such as hayfever and allergic dermatits . increased expression of eotaxin has been observed in these conditions , as well . thus another aspect of this invention is a method to decrease the symptoms of allergic rhinitis or sinusitis by administering a eotaxin - reducing effective amount of 25 - oh d3 to a person in need of such reduction . the resulting reduction of eosinophil aggregation would lead to an observable reduction in symptoms of rhinitis or sinusitis , including decrease in swelling and inflammation . another aspect of this invention is the use of 25 - oh d3 in the method of making a medicament suitable for rhinitis or sinusitis . the 25 - oh d3 may be used as an adjunct to or in co - therapy with known rhinitis or sinusitis medicaments and / or therapies . thus another aspect of this invention is a method to decrease the symptoms of or hayfever or allergic dermatitis by administering a eotaxin - reducing effective amount of 25 - oh d3 to a person in need of such reduction . the resulting reduction of eosinophil aggregantion would lead to an observable reduction in symptoms of hayfever or allergic dermatis , including decrease in swelling and inflammation . another aspect of this invention is the use of 25 - oh d3 in the method of making a medicament suitable for hayfever or allergic dermatitis . the 25 - oh d3 may be used as an adjunct to or in co - therapy with known hayfever or allergic dermatitis medicaments and / or therapies . chronic inflammatory diseases of the nose and sinuses can lead to the formation of nasal polyps , and this involves an up - regulation of eotaxin ( see rankin et al 2000 molecular medicine today 6 : 20 - 27 , which is hereby incorporated by reference . administration of 25 - oh d3 , and / or vitamin d3 , in accordance with this invention will decrease eotaxin levels , and thus ameliorate , prevent or treat the formation and growth of nasal polyps . the 25 - oh d3 may be used as an adjunct to or in co - therapy with known medicaments and / or therapies for nasal polyps . normally , eosinophils are not found in the esophageal mucosa , but it some disease states , they can accumulate there , having a proinflammatory effect . there are several gastric disorders which involve the presence of eosinophils and increased eotaxin in the gut : normally , eosinophils are not found in the esophageal mucosa , but it esinophilic esophagitis , they can accumulate there , having a pro - inflammatory effect . symptoms include dysphagia , chest pain and food impaction . in children , it can include nausea and vomiting , weight loss , anemia and failure to thrive . often patients have a history of allergies , including food allergies to high protein foods such as milk , eggs , soybean , wheat , chicken and nuts . the eosinophils in the esophageal mucosa release major basic protein , which induces smooth muscle contractions , that are thought to be mechanistically similar to the broncho - constriction observed in asthma . thus , reducing the amount of eotaxins would ameliorate the symptoms of eosinophilic esophagitis . thus another aspect of this invention is a method to decrease the symptoms of eosinophilic esophagitis by administering a eotaxin - reducing effective amount of 25 - oh d3 to a person in need of such reduction . the resulting reduction of eosinophil aggregantion would lead to an observable reduction in symptoms of eosinophilic esophagitis , including decrease in smooth muscle contraction , dysphagia , chest pain , food impaction , nausea , and vomiting . another aspect of this invention is the use of 25 - oh d3 in the method of making a medicament suitable for eosinophilic esophagitis . the 25 - oh d3 may be used as an adjunct to or in co - therapy with known eosinophilic esophagitis medicaments . eosinophils have been implicated in the pathogenesis of iba ( see wedemeyer et al 2008 best practice & amp ; res clin gastroenterol 22 ( 3 ): 537 - 549 , which is hereby incorporated by reference . active inflammation has been associated with increased eosinophils at the site of inflammation . the release of their proteins ( including eosinophil granule cationic protein ) can cause tissue damage . thus , lowering the level of eotaxin would result in a loss of eosinophil aggregation , leading to a reduction of symptoms of iba , including inflammation . thus another aspect of this invention is a method to decrease the symptoms of irritable bowel syndrome by administering a eotaxin - reducing effective amount of 25 - oh d3 to a person in need of such reduction . the resulting reduction of eosinophil aggregation would lead to an observable reduction in symptoms of iba , including a decrease in inflammation . another aspect of this invention is the use of 25 - oh d3 in the method of making a medicament suitable for iba . the 25 - oh d3 may be used as an adjunct to or in co - therapy with known iba therapies . crohn &# 39 ; s disease and ulcerative colitis are chronic inflammatory diseases , but no specific pathogen has been identified . like ibs , they are characterized by increased levels of eosinophils . it has been shown that eotaxin - deficient mice had a reduced amount of eosinophils in the colon , and exhibit a significantly attenuated colitis compared to wild - type . thus another aspect of this invention is a method to decrease the symptoms of crohn &# 39 ; s disease or ulcerative colitis by administering a eotaxin - reducing effective amount of 25 - oh d3 to a person in need of such reduction . the resulting reduction of eosinophil aggregantion would lead to an observable reduction in symptoms of crohn &# 39 ; s disease or ulcerative colitis , including decrease in swelling and inflammation . another aspect of this invention is the use of 25 - oh d3 in the method of making a medicament suitable for crohn &# 39 ; s disease or ulcerative colitis . the 25 - oh d3 may be used as an adjunct to or in co - therapy with known crohn &# 39 ; s disease or ulcerative colitis therapies . hogan et al 2004 aliment phannacol ther 20 : 1231 - 1240 , which is hereby incorporated by reference , propose that reduction of eosinophils would be beneficial in other gastrointestinal conditions , including food allergies , parasitic infections , and gastro - esophageal reflux . food dosages : the rda which is in place at the time the food is sold is the maximum dosage of the combination of vitamin d3 + 25 - oh d3 recommended to be incorporated into a food currently , the rda for vitamin d3 is : 400 iu for infants ( 0 - 12 months ) 600 iu for children (+ 1 year ) through adolescents and adults ( 70 years ) 800 iu for adults (+ 71 years ) 600 iu for pregnant or lactating women for 25 - oh d3 alone , there is not a current rda , as in some countries , regulations do not permit it to be added to human food ; however it is considered to be approximately 3 × as active as vitamin d3 . thus , for food use , the maximum dose which should be present in a food is approximately 3 × less than the rda of vitamin d3 . it is noted that conventionally vitamin d3 dosages are expressed in ius , whereas 25 - oh d3 dosages are expressed in μg . the amounts are readily converted , as one iu vitamin d3 is equal to 40 μg . daily . a composition according to this invention where the two active ingredients are to be administered separately , or alone contains vitamin d or 25 - oh d3 in an amount from about 1 μg to about 50 μg , preferably about 5 μg and 25 μg . alternatively , a single daily dosage having both vitamin d and 25 - oh d3 contains each active ingredient in an amount from about 1 μg to about 50 μg , preferably about 5 μg and 25 μg . the dosage ratio of vitamin d to 25 - oh d3 may be from about 50 : 1 to about 1 : 50 , more preferably from about 25 : 1 to about 1 : 25 , and even more preferably from about 6 : 1 to about 1 : 6 . multiple , separate dosages may be packaged in a single kit ( or container ). for example , the kit may be comprised of thirty separate daily dosages of both actives separately ( i . e . 60 separate dosages ), or combined ( i . e . 30 dosages containing both active ingredients ). instructions for administering the dosages to a human may be included in the kit . weekly . a single weekly dosage contains vitamin d or 25 - oh d3 in an amount from about 7 μg to about 350 μg , and preferably from about 35 to 175 μg . alternatively , a single weekly dosage may contain both vitamin d and 25 - oh d3 each in an amount from about 7 μg to about 350 μg , and preferably from about 35 to 175 μg . the dosage ratio of vitamin d to 25 - 0h d3 may be from about 50 : 1 to about 1 : 50 , more preferably from about 25 : 1 to about 1 : 25 , and even more preferably from about 6 : 1 to about 1 : 6 . monthly . a single monthly dosage contains vitamin d or 25 - oh d3 in an amount from 30 μg to about 1500 μg , preferably about 75 μg to about 500 μg . alternatively , a single monthly dosage may contain both vitamin d and 25 - oh d3 each in an amount from 30 μg to about 1500 μg , preferably about 75 μg to about 500 μg . a kit may be comprised of one , two , three , four , five , six , seven , eight , nine , ten , eleven , or twelve weekly or monthly dosages . dosage ratios of vitamin d to 25 - oh d3 should range between 50 : 1 to about 1 : 50 , more preferably from about 25 : 1 to about 1 : 25 , and even more preferably from about 6 : 1 to about 1 : 6 . bolus : a single bolus dosage contains vitamin d or 25 - oh d3 in an amount from 30 μg to about 7500 μg , alternatively , a single bolus dosage may contain both vitamin d and 25 - oh d3 each in an amount from 100 μg to about 7500 μg , ( preferably about 75 μg to about 3750 μg ). dosage ratios of vitamin d to 25 - oh d3 should range between 50 : 1 to about 1 : 50 , more preferably from about 25 : 1 to about 1 : 25 , and even more preferably from about 6 : 1 to about 1 : 6 . bolus dose can be followed by a daily or weekly or monthly regimen as described above . there is a scarcity of data on the relationship between orally - administered 25 - hydroxyvitamin d3 and its resulting systemic concentration in humans , in comparison to orally - administered vitamin d3 . the most comprehensive analysis to date of the kinetics of vitamin d3 and 25 - hydroxyvitamin d3 was conducted by barger - lux et al . ( osteoperosis 8 : 222 - 230 , 1998 ). healthy men were administered up to 1250 μg / day of vitamin d3 over a period of eight weeks , and up to 50 μg / day of 25 - hydroxyvitamin d3 over a period of four weeks . curvilinear kinetics were demonstrated for the relationship of vitamin d3 and plasma 25 - hydroxyvitamin d3 , and it was suggested that this may be due to saturation of hydroxylase activity in the liver . this was supported in that dosing with 25 - hydroxyvitamin d3 was not reported as producing curvilinear kinetics ( barger - lux et al ., 1998 ). although data on 25 - hydroxyvitamin d3 does show curvilinear kinetics , it is only evident when the dose is extended past the level considered to result in maximum physiological benefit , which may indicate the activity of a homeostatic mechanism that is overwhelmed at very high doses . within the physiological range , the relationship appears linear and comparable to barger - lux et al . these data indicate that a daily dose of between 10 μg and 60 μg of 25 - hydroxyvitamin d is required for maximum health benefit . a study of the pharmacokinetics in humans of orally - administered spray - dried 25 - hydroxyvitamin d3 , spray - dried vitamin d3 , or both was initiated to investigate their physiological interactions . in particular , the shapes of their dose - response curves ( which indicates the concentrations of vitamin d3 and 25 - hydroxyvitamin d3 in the circulation over a set time course , not simply the average or maximum concentration achieved ) and the steady - state kinetics were of interest . in respect of the former point , it is important to investigate the change in shape of the dose - response curves when exposure is to both vitamin d3 and 25 - hydroxyvitamin d3 . in respect of the latter point , it is also necessary to investigate their steady - state kinetics when dosing is less frequent than daily because this is the preferred regimen for groups that may have low compliance with taking daily supplements ( such as the elderly ). the following non - limiting examples are presented to better illustrate the invention . healthy , postmenopausal women ( 50 to 70 years of age ) were recruited using informed consent and screened using the following criteria : serum 25 - hydroxy vitamin d3 between 20 nmol / l and 50 nmol / l , body mass index between 18 kg / m 2 and 27 kg / m 2 , blood pressure less than 146 / 95 mm hg , serum calcium less than 2 . 6 nmol / l , fasting glucose less than 100 mg / dl , no high - intensity exercise more than three times per week , no treatment for hypertension , no use of high - dose vitamin d or calcium supplement or drug affecting bone metabolism ( e . g ., biphosphonate , calcitonin , estrogen receptor modulator , hormone replacement therapy , parathyroid hormone ), and not visiting a “ sunny ” location during the study . subjects were randomly assigned to one of seven treatment groups ( i . e ., daily , weekly , bolus as single dose , and bolus as combination dose ). each group included five subjects . they were followed for four months in zürich , switzerland during the winter . the objective was studying and comparing the pharmacokinetic characteristics of vitamin d3 and 25 - hydroxyvitamin d3 administered to humans . equimolar quantities of both substances were investigated . the regimen was based on 20 μg / day ( or its equivalent on a weekly basis ) of 25 - hydroxyvitamin d3 . for comparative purposes , it was necessary to administer equimolar quantities of either vitamin d3 or 25 - hydroxyvitamin d3 . in respect to administration of vitamin d3 , the dose was considered to be sufficient to overcome background variability and provide and efficacious dose to the participants . daily : 120 administrations 1 . 25 - hydroxyvitamin d3 20 μg 2 . vitamin d3 20 μg ( 800 iu ) weekly : 16 administrations 3 . 25 - hydroxyvitamin d3 140 μg 4 . vitamin d3 140 μg ( 5600 iu ) bolus : single administration 5 . 25 - hydroxyvitamin d3 140 μg 6 . vitamin d3 140 μg ( 5600 iu ) bolus : combo administration 7 . d3 and 25 ( oh ) d3 140 μg ( 5600iu ) + 140 μg hard gel capsules , which are packaged in bottles , contain either 20 μg or 140 μg of either spray - dried vitamin d3 or 25 - hydroxyvitamin d3 per capsule . each dosage was consumed orally at breakfast . the duration of the study was four months for the “ daily ” and “ weekly ” groups . subjects enrolled in the “ bolus ” group consumed orally a single dosage at the second study visit . plasma concentrations of 25 - hydroxyvitamin d3 ( e . g ., peak and steady state ) were determined by obtaining samples from the subjects at various times after the dosage was ingested . for screening purposes and to establish baseline values , a blood sample was obtained prior to enrollment into the study and the clinical laboratory measured vitamin d3 , 25 - hydroxyvitamin d3 , calcium , creatinine , albumin , and fasting glucose in the serum . on monday of week 1 of the study , pharmacokinetics of serum vitamin d3 , 25 - hydroxyvitamin d3 , and 1 , 25 - dihydroxy vitamin d3 ; serum markers ( i . e ., vitamin d3 , 25 - hydroxyvitamin d3 , calcium , creatinine , albumin , pth , got , gpt , alp , triglycerides , hdl , ldl , total cholesterol , balp , and fasting glucose ); and urine markers ( i . e ., calcium , creatinine , and dpd ) were assessed over 24 hours . daily samples for the remaining days of week 1 and monday of week 2 were taken to assess serum vitamin d3 and 25 - hydroxyvitamin d3 , serum markers ( i . e ., calcium , creatinine , albumin ), and urine markers ( i . e ., calcium , creatinine ). the assessments continued on monday of weeks 3 , 5 , 7 , 9 , 11 , 13 and 15 . on monday of week 16 , samples were taken to assess pharmacokinetics of serum vitamin d3 , 25 - hydroxyvitamin d3 , and 1 , 25 - dihydroxy vitamin d3 ; serum markers ( i . e ., vitamin d3 , 25 - hydroxyvitamin d3 , calcium , creatinine , albumin , pth , got , gpt , alp , triglycerides , hdl , ldl , total cholesterol , balp , and fasting glucose ); and urine markers ( i . e ., calcium , creatinine , and dpd ). twenty healthy postmenopausal women with 25 - hydroxyvitamin d3 levels below 25 ng / ml and a mean age of 61 . 5 years ( sd ± 7 . 2 ) were enrolled in this study . participants were randomized to either 20 μg of oral 25 - hydroxyvitamin d3 or 20 μg of vitamin d 3 per day in a double - blind manner . on 14 visits over 4 months , 25 ( oh ) d levels , and 7 inflammation markers ( eotaxin , il - 8 , il - 12 , ip - 10 , mcp - 1 , mip - 1β , rantes ) were measured . all analyses were adjusted for baseline , age and body mass index . mean 25 ( oh ) d levels increased from 13 . 7 to 69 . 5 ng / ml in the 25 - hydroxyvitamin d3 group ( not shown ). for vitamin d 3 , 25 ( oh ) d levels increased from 13 . 5 to 31 . 0 ng / ml with a slow increase over time . levels of inflammatory markers were determined at baseline and the end of the follow - up period . for most of the markers baseline levels vary considerably within a population of healthy individuals ( see e . g . campell et al human immunology vol 62 , p . 668 - 678 , 2001 ). yet , they increase during periods of infection or health deteriorations . for instance eotaxin levels significantly increase in individuals during episodes of asthma or allergy ( campell et al . international immunology vol . 14 , p . 1255 - 1262 , 2002 ). while both types of vitamin d supplementation contributed to a decrease in 5 out of 7 inflammation markers , only eotaxin levels were significantly more reduced by 25 - hydroxyvitamin d3 compared to vitamin d3 ( p = 0 . 003 ) at the end of the intervention phase . it should be noted that relative changes of different inflammatory markers ought be considered to reflect a positive impact on health rather than absolute levels , since these depend on the sensitivity of the analytical methods used . the results demonstrate the selective effect of 25 - hydroxyvitamin d3 on the levels of the inflammatory marker eotaxin .
the present invention relates to treating / preventing conditions associated with an increased level of eotaxin in a human with 25 - hydroxyvitamin d3 . optionally , vitamin d3 may be used together with 25 - hydroxyvitamin d3 .