A review select vitamins minerals used by postmenopausal women绝经后妇女使用的维生素和矿物质综述.pdf

Maturitas 66(2010)370380Contents lists available at ScienceDirectMaturitasjournal homepage: review of select vitamins and minerals used by postmenopausal womenCathi Dennehya,Candy TsourounisbaDepartment of Clinical Pharmacy,UCSF School of Pharmacy,521 Parnassus Ave,Suite C-152,Box 0622,San Francisco,CA 94143,USAbMedication Outcomes Center,Department of Clinical Pharmacy,UCSF School of Pharmacy,521 Parnassus Ave,Suite C-152,Box 0622,San Francisco,CA 94143,USAa r t i c l ei n f oArticle history:Received 20 April 2010Received in revised form 1 June 2010Accepted 2 June 2010Keywords:VitaminsMineralsPostmenopausalWomenSupplementDietarya b s t r a c tObjectives:The purpose of this review is to summarize the effectiveness of select vitamins,minerals andtrace elements in postmenopausal women for their effects on bone health,cardiovascular health,breastcancer,cognition and vasomotor symptoms.Methods:Review of the relevant literature and results from recent clinical studies,as well as criticalanalyses of published systematic reviews and meta-analyses were obtained from PubMed and CochraneLibraryofReviews.VitaminA,theBvitamins,vitaminC,calcium,vitaminD,vitaminE,vitaminK,magne-sium,selenium and zinc were selected for review.In circumstances where the vitamin,mineral or traceelement has not been studied for a given condition,no information was provided.Results and discussion:All vitamins,minerals and trace elements play an important role in maintaininghealth and wellbeing among menopausal women.Adequate dietary intake is essential and supplementa-tion should be considered in women with documented malabsorption syndromes or deficiencies.Basedonareviewoftheliterature,supplementationwithvitaminC,D,Kandcalciumcanalsoberecommendedfor proper maintenance of bone health.The only supplement studied for vasomotor symptoms was vita-minEandthisvitaminlackedclinicalsupport.Supplementationinhealthypostmenopausalwomenwithvitamins and minerals in diet or pill forms cannot be recommended currently for any other indications.Published by Elsevier Ireland Ltd.Contents1.Introduction.3712.Methods.3713.Vitamin A.3723.1.Nutrient sources and actions.3723.2.Clinical efficacy.3723.2.1.Bone health.3723.2.2.Cardiovascular health.3723.2.3.Breast cancer.3724.B vitamins.3734.1.Nutrient sources and actions.3734.2.Clinical efficacy.3744.2.1.Bone health.3744.2.2.Cardiovascular health.3744.2.3.Breast cancer.3744.2.4.Cognition.3745.Vitamin C.3755.1.Nutrient sources and actions.3755.2.Clinical efficacy.3755.2.1.Bone health.3755.2.2.Cardiovascular health.3755.2.3.Breast cancer.3755.2.4.Cognition.375Corresponding author.Tel.:[phone];fax:[phone].E-mailaddresses:dennehycpharmacy.ucsf.edu(C.Dennehy),tsourouniscpharmacy.ucsf.edu(C.Tsourounis).0378-5122/$see front matter.Published by Elsevier Ireland Ltd.doi:10.1016/j.maturitas.2010.06.003C.Dennehy,C.Tsourounis/Maturitas 66(2010)3703803716.Vitamin D and calcium.3756.1.Nutrient sources and actions.3756.2.Clinical efficacy.3756.2.1.Bone health.3756.2.2.Cardiovascular health.3766.2.3.Breast cancer.3766.2.4.Cognition.3767.Vitamin E.3767.1.Nutrient sources and actions.3767.2.Clinical efficacy.3767.2.1.Cardiovascular health and breast cancer.3767.2.2.Cognition.3767.2.3.Vasomotor symptoms.3768.Vitamin K.3778.1.Nutrient sources and actions.3778.2.Clinical efficacy.3778.2.1.Bone health.3778.2.2.Cardiovascular health.3779.Magnesium.3779.1.Nutrient source and actions.3779.2.Clinical efficacy.3779.2.1.Bone health.3779.2.2.Cardiovascular health.37710.Selenium.37710.1.Nutrient sources and actions.37710.2.Clinical efficacy.37810.3.Risks of high selenium exposure.37811.Zinc.37811.1.Nutrient source and actions.37811.2.Clinical efficacy.37811.2.1.Cardiovascular health.37811.2.2.Cognition.378Contributors.378Competing interests.378Provenance and peer review.378References.3781.IntroductionThis review focuses on the effects of vitamin and mineralsupplementation in postmenopausal women with an emphasis onbone health,cardiovascular health,breast cancer risk,cognitionand vasomotor symptoms.The 2007 National Health InterviewSurvey identified women,ages 5069,residing in the westernUnited States(US)as more consistent users of complementary andalternative medicine(CAM)and estimated that 18%of adults wereusing non-vitamin,non-mineral natural products 1.The sale ofvitamins and minerals exceeds that of other dietary supplementcategories so it can be assumed that the use of vitamins andminerals among adults exceeds the 18%reported in the NHANESsurvey 1.In a survey of 563 menopausal women living in theUS who had discontinued hormone replacement therapy,45%were using CAM therapies to treat vasomotor symptoms;multi-vitamins and calcium were the most prevalent subgroup at 27%2.Intake recommendations for vitamins and minerals are set bythe National Academy of Sciences,Institute of Medicine Food andNutritionBoard(FNB)asDietaryReferenceIntakes(DRIs)3.Termsthat healthcare providers should be familiar with include Recom-mended Dietary Allowance(RDA)which refers to the average dailyintake needed to meet the needs of 97.5%of individuals at that par-ticular gender and life stage,Adequate Intake(AI)which refers tothe daily intake needed to meet the needs of almost all healthyindividuals and Tolerable Upper Intake Level(UL)which refers tothe maximum daily intake unlikely to produce adverse effects.AIvalues are used when there is insufficient data to formulate an RDArecommendation.Table 1 summarizes these values for all of thevitamins and minerals reviewed,specifically among healthy post-menopausalwomen.Table2summarizesrecommendationsforuseof these vitamins and minerals in this population.2.MethodsPubMed(MEDLINE)and the Cochrane Library of Reviewswere searched for relevant systematic reviews and meta-analysesfrom 1966 to February 2010.In the absence of systematicreviews or meta-analyses,individual randomized controlled tri-als,prospective and retrospective cohort studies were used.Incircumstanceswherenointerventionstudieswereavailable,obser-vational/epidemiologicalstudieswerereviewed.Searchtermsusedto capture common names and scientific names of vitamins andminerals were based on Medical Subject Heading terms and textwords from previously identified key articles.The following keywords were used:vitamin A,retinoids,retinol,carotenoids,B vita-mins,folate,vitamin B12,cyanocobalamin,vitamin B6,pyridoxine,vitamin C,ascorbic acid,calcium,vitamin D,vitamin E,tocopherol,vitamin K,phylloquinone,menaquinone,magnesium,seleniumand zinc.For each substance,the following terms were searched:menopause,postmenopausal,heart disease,cardiovascular dis-ease,coronary heart disease,bone health,osteoporosis,bonemineral density,osteopenia,cognition,memory,dementia,vaso-motor symptoms,hot flash,and breast cancer.We restricted thesearch to articles published in English,studies involving humans,and studies of adult women aged 45 years or older.We applied thesame search strategy to both databases.In circumstances where372C.Dennehy,C.Tsourounis/Maturitas 66(2010)370380Table 1Daily recommended intake of vitamins and minerals in postmenopausal women.Vitamin or mineralRecommended intakeaUpper limitVitamin ARDA700mcgRAEb/2310IU3000mcg RAEb/10,000IUFolateRDA400mcg1000mcgVitamin B6RDA age 19501.3mg100mgRDA age 51+1.5mg100mgVitamin B12RDA2.4mcgNot establishedcVitamin CRDA75mg2000mgVitamin D(1mcg calciferol=40IU)AI age 5170AI age 71NOFd10mcg(400IU)15mcg(600IU)2025mcg(8001000IU)50mcg(2000IUe,d)CalciumAI1200mg20002500mgbVitamin ERDA15mg(22.4IU)c1000mg(1490IU)cVitamin KAI90mcgNot establishedfMagnesiumRDA320mg350mgSeleniumRDA55mcg400mcgZincRDA8mg40mgaRDA or AI is set by the Institute of Medicine,Food and Nutrition Board.bNOF,National Osteoporosis Foundation recommendations.cCorresponds to natural form where 1mg of alpha-tocopherol is equivalent to 1.49IU.An equivalent amount of synthetic alpha-tocopherol would be 2.22IU per milligram.dRAE,retinol activity units.eThe tolerable upper limit of vitamin D may be higher than this and is currently in question.fNo established level of toxicity in healthy individuals from food and supplemental intake.the vitamin,mineral or trace element had not been studied for agiven condition,no information was provided.3.Vitamin A3.1.Nutrient sources and actionsVitaminAreferstoagroupofcompoundscalledretinoidswhichplay an important role in vision,bone growth,reproduction,celldivision and cell differentiation 4.Retinoids are active as retinal,retinoic acid and retinol.Retinal is actively involved in support-ing vision,retinoic acid regulates cell differentiation,growth andembryonic development and retinol is responsible for transportand storage 5.Two forms of vitamin A are found in plants and animals,provitamin A and preformed vitamin A,respectively.Vitamin Afound in fruits and green leafy vegetables is called provitamin Acarotenoid which is converted into retinol once ingested.The mostcommon provitamin A carotenoids found in foods include beta-carotene,alpha-carotene and beta-cryptoxanthin.Among these,beta-caroteneisthemostefficientlyconvertedintoretinol.VitaminA found in foods derived from animal sources is called preformedvitamin A and is absorbed as retinol.Liver,whole milk,andselect fortified foods are good sources.Interestingly,non-fat milklacks adequate vitamin A and therefore non-fat milk is fortifiedwith vitamin A.Breakfast cereals are also fortified with vitaminA.Preformed vitamin A is the form supplied by most supple-ments.VitaminAdeficiencyisrarelyobservedinUS;however,patientswith fat malabsorption,cystic fibrosis,celiac disease,cholestaticliver disease,Crohns and pancreatic insufficiency are at risk.3.2.Clinical efficacy3.2.1.Bone healthIn a prospective cohort study of postmenopausal women,high dietary intake of vitamin A(3000?g/day)for 18 yearswas associated with an increased risk of osteoporotic fractures6.This increased risk was observed only in women not usingpostmenopausal hormones.Among the Womens Health Initia-tive Study(WHIS)involving more than 75,000 postmenopausalwomen,no association was observed at three years between vita-min A or retinol intake(mean 1149?g/day from supplements andmean 6400?g/day total intake)and risk of hip or total fractures.The authors did observe a modest increase in total fracture riskwith high vitamin A and retinol intake among the low vitaminD intake group(11?g/day)7.Among a cohort from the IowaWomens Health Study of postmenopausal women,there was nodoseresponse relationship between hip fracture risk and increas-ing amounts of vitamin A or retinol intake either from food aloneor food and supplements 8.These findings suggest more researchis needed to determine whether vitamin A or retinol intake is asso-ciated with an increase in fracture risk.3.2.2.Cardiovascular healthHigh levels of two specific carotenoids(B-cryptoxanthin andlutein)were associated with a decreased risk of acute myocar-dial infarction(MI)among a Chinese cohort of women aged 4574years9.WhethervitaminAsupplementationhasaprotectivecar-diovascular effect among postmenopausal women and whetherthis effect is more pronounced in women with low or normalretinol levels remains unstudied.It is also unknown whether vita-min A supplementation would offer a similar benefit for primaryor secondary prevention of MI among all postmenopausal womenregardless of geographic or ethnic origin.3.2.3.Breast cancerMany longitudinal cohort studies have assessed carotenoidintake and endogenous retinol levels and the risk for developingbreast cancer among postmenopausal women from multiple eth-nic groups and geographic locations worldwide 5,1014.Amongpostmenopausal women,select studies have concluded that intakeofcarotenoidsandretinollevelsarenotassociatedwithbreastcan-cerrisk5,1012,15.Whenindividualcarotenoidswereevaluated,however,lycopene was associated with a reduction in breast can-cer risk among postmenopausal women 10,15,16.Data from theWHIS suggests that lycopene was specifically protective amongEstrogen Receptor Positive(ER+),Progesterone Receptor Positive(PR+)breast cancer 16.In contrast,one longitudinal study con-cluded that increased lycopene levels were associated with anincreased risk of breast cancer 13.C.Dennehy,C.Tsourounis/Maturitas 66(2010)370380373Table 2Recommendations for supplementation with specific vitamins and minerals in healthy postmenopausal women.a.Vitamin or mineralAuthors interpretation of level ofevidence for use in a clinical settingbConcerns/side effectsAdditional informationVitamin ABone health(NR)Cardiovascular(U)Breast cancer(U)Concern over possible fracture riskwith highcintake,may be more likelyin setting of low vitamin D levelsVitamin A is stored in the liver andexcessive intake may lead tohypervitaminosis AResearch on individual carotenoids isneededTemporary periods of malabsorptionshould not lead to overt deficiencydVitamin B6,B12,folateBone health(U)Cardiovascular(NR)Breast cancer(NR)Cognition(U)NoneSupplementation may homocysteinelevelsFolate supplementation in specificcases of alcoholism,liver disease orkidney dialysis is recommendedVitamin CBone health(R)Cardiovascular(NR)Breast cancer(NR)Cognition(U)Osmotic diarrhea,nausea and stomachcramps more common at doses3G/daydNoneVitamin DBone health(R)Cardiovascular(NR)Breast cancer(NR)Cognition(U)Rarely associated with hypercalcemia,hypercalciuria or kidney stoneseLow vitamin D status has been linkedto several primary disease statesCalciumBone health(R)Cardiovascular(U)Breast cancer(NR)Stomach upset(e.g.constipation,gas,bloating)may occur,rarely linked tokidney stones,renal insufficiency orhypercalcemiafDosing based on elemental calciumintake,separate doses for bothformulationsfCalcium carbonate is the leastexpensive formulation;take with foodfor optimal absorptionfCalcium citrate is preferred in personstaking acid suppressants or who havereduced levels of stomach acidfVitamin ECardiovascular(NR)Breast cancer(NR)Cognition(U)Hot flushes(NR)Anti-platelet effects warrant cautioususe in patients taking blood thinnersAvoid doses in excess of 400IU/daydue to concern over risk of all causemortalitySynthetic vitamin E is less potent thannatural vitamin E,conversion rates arelisted in Table 1Vitamin KBone health(R)gCardiovascular(U)Rarely may cause stomach upset,constipation,and body weight gainhUse may lead to reversal of warfarineffectMagnesiumBone health(U)Cardiovascular(U)DiarrheadMagnesium supplementation shouldbe considered in specific cases ofalcoholism,ischemic heart disease,cardiac arrhythmias,and electrolytedisordersdSeleniumCardiovascular(NR)Cognition(NR)Excessive selenium levels may increasethe risk of several disease states(e.g.hyperlipidemia,hypertension,diabetes)Dietary selenium status should beassessed prior to beginning anysupplementationZincCardiovascular(U)Cognition(U)Gastrointestinal upset can occur,takewith food to minimizedZinc supplementation should beconsidered in specific cases ofalcoholism and high fiber diets rich inphytates(e.g.nuts,seeds,grains)daRecommendations are ba