Anemia in old age
Elzen, W.P.J. den
Citation
Elzen, W. P. J. den. (2010, November 2). Anemia in old age. Retrieved from https://hdl.handle.net/1887/16106
Version: Corrected Publisher’s Version
License: Licence agreement concerning inclusion of doctoral thesis in the
Appendices
A d. 1 0 P ub M ed Cl in ic al Q ue rie s; Etio lo gy ; B roa d, se nsitiv e se ar ch A d. 1 1 P ubM ed C lin ical Qu er ies; E ti ol ogy ; Nar ro w , sp eci fi c sear ch A d. 12 P ub M ed Cl in ic al Q ue rie s; T he ra py ; Br oa d, s ensitiv e se arc h A d. 1 3 P ubM ed C lin ical Qu er ies; Th er ap y; Nar ro w , sp eci fi c s ear ch
#1 6 L im its: En glis h, Fre nc h, G er m an , D utc h #1 7
#15 N OT cas e r ep or ts N OT let ter #1 6
#10 O R #1 1 OR #1 2 OR # 13 OR # 14 #1 5
(# 9) A ND s ys te m at ic[ sb] #1 4
(#9 ) A N D (r and om iz ed c on tro lle d tria l[ P ub lic atio n T yp e] O R (r an dom iz ed[ T itle /A bstra ct] A N D c on trol le d[ T itle /A bs tra ct tria l[ T itle /A bstra ct] )) #1 3 (#9 ) A N D (( clinic al[ T itl e/A bs tra ct] A N D tria l[ T itle /A bstra ct] ) O R c lini ca l tria ls [Me SH T er m s] O R c linic al tria l[ P ub lic ati Ty pe] O R ra ndo m *[ T itle /A bs tra ct] O R ra nd om a llo ca tion [Me SH T er m s] OR th er ape ut ic u se [Me SH S ub he adin g] ) #1 2 (#9 ) A N D (( re lativ e[ T itl e/ A bstra ct ] A N D r is k* [T itle/A bs tra ct] ) O R (r el ativ e r isk [T ex tW ord] ) OR ris ks[ T ex tW ord] O R st udi es [M eSH :no ex p] O R (c oho rt [T itle /A bstr ac t] A N D s tu d* [T itle /A bstr ac t] )) #1 1 (#9 ) A N D (r is k* [ T itle /A bstra ct] OR ris k* [ M eS H :n oe xp] O R ris k * [Me SH :n oex p] O R c oh ort s tud ie s[ Me S H T erm s] OR grou p* [T ex t W or d] ) #1 0
#4 A N D #8 #9
#5 O R #6 O R # 7 #8
an em i* [t w ] OR an aem i* [t w ] OR h em ogl ob in *[ tw ] OR h aem og lo bi n* [t w ] #7
He m ogl ob in s[ M eS H ] #6
An em ia [M eS H ] #5
#1 O R #2 O R # 3 #4
vita m in B12 [tw ] OR v ita m in B 1 2[ tw ] O R c ob ala m in *[ tw ] O R cy an oc oba la m in *[ tw ] O R h ydro xo cob al am in *[ tw ] O R hy drox yc oba la m in *[ tw ] #3
V it am in B 12 d ef ici en cy [M eS H ] #2
V ita m in B 1 2[ Me SH ] #1
A ppe nd ix 1 . Stra te gy use d to se arc h P ub M ed da ta ba se f or p ub lic at ion s on sub norm al v ita m in B12 le ve ls an d a ne m ia (c arr ied ou t O c ] A N D
on coh ort
to be r 20 09) A d. 1 0 P ub M ed Cl in ic al Q ue rie s; Etio lo gy ; B roa d, se nsitiv e se ar ch A d. 1 1 P ubM ed C lin ical Qu er ies; E ti ol ogy ; Nar ro w , sp eci fi c sear ch A d. 12 P ub M ed Cl in ic al Q ue rie s; T he ra py ; Br oa d, s ensitiv e se arc h A d. 1 3 P ubM ed C lin ical Qu er ies; Th er ap y; Nar ro w , sp eci fi c s ear ch
#1 6 L im its: En glis h, Fre nc h, G er m an , D utc h #1 7
#15 N OT cas e r ep or ts N OT let ter #1 6
#10 O R #1 1 OR #1 2 OR # 13 OR # 14 #1 5
(# 9) A ND s ys te m at ic[ sb] #1 4
(#9 ) A N D (r and om iz ed c on tro lle d tria l[ P ub lic atio n T yp e] O R (r an dom iz ed[ T itle /A bstra ct] A N D c on trol le d[ T itle /A bs tra ct tria l[ T itle /A bstra ct] )) #1 3 (#9 ) A N D (( clinic al[ T itl e/A bs tra ct] A N D tria l[ T itle /A bstra ct] ) O R c lini ca l tria ls [Me SH T er m s] O R c linic al tria l[ P ub lic ati Ty pe] O R ra ndo m *[ T itle /A bs tra ct] O R ra nd om a llo ca tion [Me SH T er m s] OR th er ape ut ic u se [Me SH S ub he adin g] ) #1 2 (#9 ) A N D (( re lativ e[ T itl e/ A bstra ct ] A N D r is k* [T itle/A bs tra ct] ) O R (r el ativ e r isk [T ex tW ord] ) OR ris ks[ T ex tW ord] O R st udi es [M eSH :no ex p] O R (c oho rt [T itle /A bstr ac t] A N D s tu d* [T itle /A bstr ac t] )) #1 1 (#9 ) A N D (r is k* [ T itle /A bstra ct] OR ris k* [ M eS H :n oe xp] O R ris k * [Me SH :n oex p] O R c oh ort s tud ie s[ Me S H T erm s] OR grou p* [T ex t W or d] ) #1 0
#4 A N D #8 #9
#5 O R #6 O R # 7 #8
an em i* [t w ] OR an aem i* [t w ] OR h em ogl ob in *[ tw ] OR h aem og lo bi n* [t w ] #7
He m ogl ob in s[ M eS H ] #6
An em ia [M eS H ] #5
#1 O R #2 O R # 3 #4
vita m in B12 [tw ] OR v ita m in B 1 2[ tw ] O R c ob ala m in *[ tw ] O R cy an oc oba la m in *[ tw ] O R h ydro xo cob al am in *[ tw ] O R hy drox yc oba la m in *[ tw ] #3
V it am in B 12 d ef ici en cy [M eS H ] #2
V ita m in B 1 2[ Me SH ] #1
A ppe nd ix 1 . Stra te gy use d to se arc h P ub M ed da ta ba se f or p ub lic at ion s on sub norm al v ita m in B12 le ve ls an d a ne m ia (c arr ied ou t O c ] A N D
on coh ort
to be r 20 09)
A d. 14 ri sk :.m p. o r ex p m et ho do log y/ or ex p epi dem io lo gy / A d. 15 (co hort o r relati ve risk :).t w . A d. 16 ran dom :.t w . or cl in ical tri al :.m p. o r ex p hea lth c are q uali ty / A d. 17 ( do ub le-b li nd: or pl ac eb o: ).m p. or b lin d: .tw . Re ference : H ea lth In fo rm at io n Re se arc h Uni t. Se arch Strateg ies f or EMBA SE in ov id sy nt ax . A cce ss ed 25 A pril 2 00 8. ht tp :/ /h ir u. m cm aster.c a/h edg es /A ll -EMBA S E .h tm
14 or 15 or 1 6 o r 1 7 18
li m it 13 to " tre atm en t (2 o r m ore ter m s hi gh s pe ci ficit y) " 17
li m it 13 to " tre atm en t (2 o r m ore ter m s hi gh s ensit iv it y) " 16
li m it 1 3 t o " ca us ati on -e tiol og y (s pe ci fi ci ty )" 15
li m it 1 3 t o " ca us ati on -e tiol og y (s ens it iv ity )" 14
11 no t 1 2 13
C as e Repo rt/ 12
li m it 10 to (d ut ch or eng lish or f rench or g erm an ) 11
5 an d 9 10
6 o r 7 or 8 9
(a ne m i$ or an ae m i$ o r he m og lob in $ or haem og lo bi n$ ).m p. [ m p= ti tl e, abstrac t, su bj ec t h ead in gs , h ead in g w ord , d rug tr ade nam ori gin al ti tle , d ev ic e m an ufac tu rer , d ru g m anu fac turer n am e] 8
exp H em ogl ob in / 7
exp An em ia / 6
1 or 2 or 3 or 4 5
(v it am in B1 2 or v it am in B 1 2) .m p. [m p= ti tl e, ab st ract, su bj ec t h ea din gs , h ea din g w ord, dr ug trade na m e, o rig in al ti tl e, dev ic e m an uf ac tur er , d rug m anu fa ct ur er na m e] 4 (c ob alam in $ or cy ano cob alam in $ or hy dro xo co bal am in $ or hy dro xy co ba la m in$ ).m p. [m p= ti tl e, a bs trac t, sub je ct headi ng s, headi w or d, dr ug tr ad e na m e, or ig in al ti tl e, de vi ce m anu fa ct ur er , dr ug m an uf ac tur er na m e] 3
C yan oco balam in D ef ic ie nc y/ 2
co bal am in/ o r cy ano cob ala m in / o r h ydro xoco balam in / 1
Appendix 2. S
tr at eg y us ed to s ea rc h E M B A S E da ta ba se f or pu bl ic at io ns on s ub no rm al v itam in B 12 le ve ls a nd a ne m ia (c ar ri ed out O ct e, ng
obe r 20 09) A d. 14 ri sk :.m p. o r ex p m et ho do log y/ or ex p epi dem io lo gy / A d. 15 (co hort o r relati ve risk :).t w . A d. 16 ran dom :.t w . or cl in ical tri al :.m p. o r ex p hea lth c are q uali ty / A d. 17 ( do ub le-b li nd: or pl ac eb o: ).m p. or b lin d: .tw . Re ference : H ea lth In fo rm at io n Re se arc h Uni t. Se arch Strateg ies f or EMBA SE in ov id sy nt ax . A cce ss ed 25 A pril 2 00 8. ht tp :/ /h ir u. m cm aster.c a/h edg es /A ll -EMBA S E .h tm
14 or 15 or 1 6 o r 1 7 18
li m it 13 to " tre atm en t (2 o r m ore ter m s hi gh s pe ci ficit y) " 17
li m it 13 to " tre atm en t (2 o r m ore ter m s hi gh s ensit iv it y) " 16
li m it 1 3 t o " ca us ati on -e tiol og y (s pe ci fi ci ty )" 15
li m it 1 3 t o " ca us ati on -e tiol og y (s ens it iv ity )" 14
11 no t 1 2 13
C as e Repo rt/ 12
li m it 10 to (d ut ch or eng lish or f rench or g erm an ) 11
5 an d 9 10
6 o r 7 or 8 9
(a ne m i$ or an ae m i$ o r he m og lob in $ or haem og lo bi n$ ).m p. [ m p= ti tl e, abstrac t, su bj ec t h ead in gs , h ead in g w ord , d rug tr ade nam ori gin al ti tle , d ev ic e m an ufac tu rer , d ru g m anu fac turer n am e] 8
exp H em ogl ob in / 7
exp An em ia / 6
1 or 2 or 3 or 4 5
(v it am in B1 2 or v it am in B 1 2) .m p. [m p= ti tl e, ab st ract, su bj ec t h ea din gs , h ea din g w ord, dr ug trade na m e, o rig in al ti tl e, dev ic e m an uf ac tur er , d rug m anu fa ct ur er na m e] 4 (c ob alam in $ or cy ano cob alam in $ or hy dro xo co bal am in $ or hy dro xy co ba la m in$ ).m p. [m p= ti tl e, a bs trac t, sub je ct headi ng s, headi w or d, dr ug tr ad e na m e, or ig in al ti tl e, de vi ce m anu fa ct ur er , dr ug m an uf ac tur er na m e] 3
C yan oco balam in D ef ic ie nc y/ 2
co bal am in/ o r cy ano cob ala m in / o r h ydro xoco balam in / 1
Appendix 2. S
tr at eg y us ed to s ea rc h E M B A S E da ta ba se f or pu bl ic at io ns on s ub no rm al v itam in B 12 le ve ls a nd a ne m ia (c ar ri ed out O ct e, ng
obe r 20 09)
*Basedonchecklists fromvan der Windt et al.23;24
6 pointsYes: Participants in lowest tertile of vitamin B12 had increased risk of anemiacompared to participants in the highest tertile (adjusted OR 1.32 (95% CI 1.03-1.70)
Method not specified. Anemia(women <110 g/L and men <120 g/L): 7%.
Chemiluminescence system. Study population divided in 3 groups based on tertiles of vitamin B12. Mean vitamin B12 in lowest tertile 167 pmol/L
Oxford Healthy Aging Project: Random sample from general practice registers for people ≥65 yearsliving in Oxford, UK, sampled in 1995. Banbury B12 Study: Random sample of people aged ≥75 years living in their own homes and registered with general practices in Banbury, Oxfordshire, UK, enrolled between March 2003 and April 2004.
≥65, mean 79.2 years (SD 6.2)
22572008Clarke29
6 pointsNo: Multivariate regression correlation coefficient vitamin B12 for Hb 0.0004 (95% CI - 0.007; 0.008)
Method not specified. Competitive radioligandmethodRandom sample of persons aged 70 years and over in the Borough of Älvkarlebyin the county of Uppsala, Sweden, sampled in 1993 and 1995
≥70, mean 78.0 (95% CI 77.2- 78.9)
224 2001Björkegren28
5 pointsUnclear: 1) Vitamin B12 concentrations did not correlate with Hb. 2) Vitamin B12 significantly lower in those who were anemic (290 vs413 pg/ml, p<0.05). 3) No relationship between vitamin B12 and MCV.
Method not specified. Anemia(women Hb<12 g/dL and men Hb<13 g/dL): 23%
Chemiluminescence method Vitamin B12 deficiency (vitamin B12<100 pg/mL[74 pmol/L]): prevalence 13%
Random sample of older Zimbabweans (rural and urban), enrolled between October 1994 and March 1995.
≥60, median 72 2331997Allain27Population-based Quality of study*
Presence of an associationHemoglobin(Hb): analysis and limits for anemia
Vitamin B12 (VitB12): analysis and limits for deficiency
Study populationAge of subjects (years)
Sample size (N)Year of publicationAuthor
Appendix 3. Observational cross-sectional studies on etiologyof vitamin B12 deficiency and anemiain older subjects included in the present review 5 points *Basedonchecklists fromvan der Windt et al.23;24
6 pointsYes: Participants in lowest tertile of vitamin B12 had increased risk of anemiacompared to participants in the highest tertile (adjusted OR 1.32 (95% CI 1.03-1.70)
Method not specified. Anemia(women <110 g/L and men <120 g/L): 7%.
Chemiluminescence system. Study population divided in 3 groups based on tertiles of vitamin B12. Mean vitamin B12 in lowest tertile 167 pmol/L
Oxford Healthy Aging Project: Random sample from general practice registers for people ≥65 yearsliving in Oxford, UK, sampled in 1995. Banbury B12 Study: Random sample of people aged ≥75 years living in their own homes and registered with general practices in Banbury, Oxfordshire, UK, enrolled between March 2003 and April 2004.
≥65, mean 79.2 years (SD 6.2)
22572008Clarke29
6 pointsNo: Multivariate regression correlation coefficient vitamin B12 for Hb 0.0004 (95% CI - 0.007; 0.008)
Method not specified. Competitive radioligandmethodRandom sample of persons aged 70 years and over in the Borough of Älvkarlebyin the county of Uppsala, Sweden, sampled in 1993 and 1995
≥70, mean 78.0 (95% CI 77.2- 78.9)
224 2001Björkegren28
Unclear: 1) Vitamin B12 concentrations did not correlate with Hb. 2) Vitamin B12 significantly lower in those who were anemic (290 vs413 pg/ml, p<0.05). 3) No relationship between vitamin B12 and MCV.
Method not specified. Anemia(women Hb<12 g/dL and men Hb<13 g/dL): 23%
Chemiluminescence method Vitamin B12 deficiency (vitamin B12<100 pg/mL[74 pmol/L]): prevalence 13%
Random sample of older Zimbabweans (rural and urban), enrolled between October 1994 and March 1995.
≥60, median 72 2331997Allain27Population-based Quality of study*
Presence of an associationHemoglobin(Hb): analysis and limits for anemia
Vitamin B12 (VitB12): analysis and limits for deficiency
Study populationAge of subjects (years)
Sample size (N)Year of publicationAuthor
Appendix 3. Observational cross-sectional studies on etiologyof vitamin B12 deficiency and anemiain older subjects included in the present review
*Basedonchecklists fromvan der Windt et al.23;24
4 pointsUnclear: 1) Vitamin B12 deficient subjects twice as likely to be anemicas the non-deficient subjects: 38% and 18%, respectively. 2) Mean (SD) Hb in vitamin B12 deficient subjects (n=24) 126 (21) g/L; in non-deficient subjects (n=79) 130 (15) g/L, NS. 3) Mean (SD) MCV in vitamin B12 deficient subjects 91.8 (4.5) fL; in non-deficient subjects 90.6 (6.6) fL, NS.
Method not specified. Anemia(women Hb<120 g/L and men Hb<130 g/L): prevalence 22%
Radioassay. Vitamin B12 deficiency: serum vitamin B12 <258 pmol/L, serum MMA >271 nmol/L, MMA concentration >methylcitricacid concentration)
Older individuals enlisted in nutrition service program in rural northeast Georgia, USA, enrolled between September 1997 and September 1998.
≥60, mean 76.4 (SD 8.1)
1032003Johnson32
5 pointsNo: 1) Symptoms of anemiawere not associated with vitamin B12 deficiency: adjusted OR 1.04 95% CI 0.67-1.61 2) 27 individuals with macrocytic anemiadid not have lower vitamin B12 than individuals who did not have macrocytic anemia.
Method not specified. Low Hb levels: <7.4 mmol/L for women and <8.4 mmol/L for men. Prevalence of anemia: 10%
Chemiluminescence method by a competitive protein binding assay. Low vitamin B12 levels: <200 pmol/L
Subjects with increased MMA (>0.28 µmol/L) within in Aarhus, Denmark, from 1995-2000.
Median 72, range 19- 102
9372005Hvas31
4 pointsNo: 1) Mean (SD) Hb for normal vitamin B12 group 13.2 (1.4) g/dL and for low vitamin B12 group 13.2 (1.2) g/dL, P>0.05 2) Mean (SD) MCV for normal vitamin B12 group 91.3 (5.0) fL and for low vitamin B12 group 92.8 (5.4) fL, P=0.0025
Standard methods (not specified).Immunoassay. Low serum vitamin B12 (<133 pmol/L): n=125, normal serum vitamin B12 levels n=875.
Random sample of people ≥75 years living at home, registered with general practitioners in Banbury, England, enrolled between March 2003 and April 2004.
≥75 s, mean 81.4 (SD 4.6)
10002006Hin30
Quality of study*
Presence of an associationHemoglobin(Hb): analysis and limits for anemia
Vitamin B12 (VitB12): analysis and limits for deficiency
Study populationAge of subjects (years)
Sample size (N)Year of publicationAuthor
Appendix 3. Observational cross-sectional studies on etiologyof vitamin B12 deficiency and anemiain older subjects included in the present review *Basedonchecklists fromvan der Windt et al.23;24
4 pointsUnclear: 1) Vitamin B12 deficient subjects twice as likely to be anemicas the non-deficient subjects: 38% and 18%, respectively. 2) Mean (SD) Hb in vitamin B12 deficient subjects (n=24) 126 (21) g/L; in non-deficient subjects (n=79) 130 (15) g/L, NS. 3) Mean (SD) MCV in vitamin B12 deficient subjects 91.8 (4.5) fL; in non-deficient subjects 90.6 (6.6) fL, NS.
Method not specified. Anemia(women Hb<120 g/L and men Hb<130 g/L): prevalence 22%
Radioassay. Vitamin B12 deficiency: serum vitamin B12 <258 pmol/L, serum MMA >271 nmol/L, MMA concentration >methylcitricacid concentration)
Older individuals enlisted in nutrition service program in rural northeast Georgia, USA, enrolled between September 1997 and September 1998.
≥60, mean 76.4 (SD 8.1)
1032003Johnson32
5 pointsNo: 1) Symptoms of anemiawere not associated with vitamin B12 deficiency: adjusted OR 1.04 95% CI 0.67-1.61 2) 27 individuals with macrocytic anemiadid not have lower vitamin B12 than individuals who did not have macrocytic anemia.
Method not specified. Low Hb levels: <7.4 mmol/L for women and <8.4 mmol/L for men. Prevalence of anemia: 10%
Chemiluminescence method by a competitive protein binding assay. Low vitamin B12 levels: <200 pmol/L
Subjects with increased MMA (>0.28 µmol/L) within in Aarhus, Denmark, from 1995-2000.
Median 72, range 19- 102
9372005Hvas31
4 pointsNo: 1) Mean (SD) Hb for normal vitamin B12 group 13.2 (1.4) g/dL and for low vitamin B12 group 13.2 (1.2) g/dL, P>0.05 2) Mean (SD) MCV for normal vitamin B12 group 91.3 (5.0) fL and for low vitamin B12 group 92.8 (5.4) fL, P=0.0025
Standard methods (not specified).Immunoassay. Low serum vitamin B12 (<133 pmol/L): n=125, normal serum vitamin B12 levels n=875.
Random sample of people ≥75 years living at home, registered with general practitioners in Banbury, England, enrolled between March 2003 and April 2004.
≥75 s, mean 81.4 (SD 4.6)
10002006Hin30
Quality of study*
Presence of an associationHemoglobin(Hb): analysis and limits for anemia
Vitamin B12 (VitB12): analysis and limits for deficiency
Study populationAge of subjects (years)
Sample size (N)Year of publicationAuthor
Appendix 3. Observational cross-sectional studies on etiologyof vitamin B12 deficiency and anemiain older subjects included in the present review
6 pointsNo: 1) Vitamin B12 not associated with hemoglobinin a multivariable linear regression analysis (men: r=-0.001, p=0.15, women: r=-0.001, p=0.32). 2) No statistically significant difference in vitamin B12 between anemicand non-anemic subjects in both sexes (men mean (SEM) vitamin B12 426.9 (319.9) pg/mLvs321.2 (119.3) pg/mL[p=0.12], women 444.6 (245.3) pg/mLvs441.9 (105.7) pg/mL[p=0.07]). 3) Prevalence of vitamin B12 deficiency similar in anemicand non-anemicsubjects: men 28% vs36% [p=0.07], women 22% vs16% [p=0.16]
Method not specified. Anemia: Hb<13.2 g/dL in men and Hb<12.2 g/dL in women. Prevalence of anemia: 83% in men and 76% in women
Method not specified. Vitamin B12 deficiency: <203.3 pg/mL
Unselected subjects older than 85 years, who were referred by general practitioners to a laboratory in Verona, Italy, for routine diagnostic check-up over a period of 2 years
Range 85- 101 8782009Lippi33 6 pointsNo: 1) Vitamin B12 deficiency more frequent in subjects with anemia than in those without anemia (15% vs8.6%, p=0.013), but adjustment for age and gender removed the effect: OR 1.3, 95% CI 0.7-2.3. 2) Vitamin B12 deficiency not associated with macrocytosis (OR 1.2 [95% CI 0.6-2.7]) and macrocytic anemia(OR 1.2 [95% CI 0.3-5.5]).
Automated hematology analyzer. Anemia(Hb women Hb <117 g/L, men Hb<134 g/L: prevalence 13%
Competitive protein binding assay. Vitamin B12 deficiency (B12<150 pmol/L, or increased tHcy (>15µmol/l) and low holoTC(<37 pmol/L)) n=97; No vitamin B12 deficiency (n=924)
Lietostudy; unselected population based health survey in Lieto, Finland. Data collected between March 1998 and December 1999.
≥65, 37% ≥75 1048 2007Loikas34 5 pointsUnclear: Prevalence of vitamin B12 deficiency 9% in anemic subjects and 5% in non-anemic subjects.
Manual cyanmethemoglobin method. Anemia(Hb<12 g/dL): prevalence 7.5% in men and 20% in women
Method using L. Leichmanii Vitamin B12 deficiency: vitamin B12 <140 pg/mL(103 pmol/L), prevalence = 5.4%
Random sample of people >65 years living at home in Kilsyth and Northern Glasgow, UK.
>653471973McLennan35 *Basedonchecklists fromvan der Windt et al.23;24
Quality of study*
Presence of an associationHemoglobin(Hb): analysis and limits for anemia
Vitamin B12 (VitB12): analysis and limits for deficiency
Study populationAge of subjects (years)
Sample size (N)Year of publicationAuthor
Appendix 3. Observational cross-sectional studies on etiologyof vitamin B12 deficiency and anemiain older subjects included in the present review 6 pointsNo: 1) Vitamin B12 not associated with hemoglobinin a multivariable linear regression analysis (men: r=-0.001, p=0.15, women: r=-0.001, p=0.32). 2) No statistically significant difference in vitamin B12 between anemicand non-anemic subjects in both sexes (men mean (SEM) vitamin B12 426.9 (319.9) pg/mLvs321.2 (119.3) pg/mL[p=0.12], women 444.6 (245.3) pg/mLvs441.9 (105.7) pg/mL[p=0.07]). 3) Prevalence of vitamin B12 deficiency similar in anemicand non-anemicsubjects: men 28% vs36% [p=0.07], women 22% vs16% [p=0.16]
Method not specified. Anemia: Hb<13.2 g/dL in men and Hb<12.2 g/dL in women. Prevalence of anemia: 83% in men and 76% in women
Method not specified. Vitamin B12 deficiency: <203.3 pg/mL
Unselected subjects older than 85 years, who were referred by general practitioners to a laboratory in Verona, Italy, for routine diagnostic check-up over a period of 2 years
Range 85- 101 8782009Lippi33 6 pointsNo: 1) Vitamin B12 deficiency more frequent in subjects with anemia than in those without anemia (15% vs8.6%, p=0.013), but adjustment for age and gender removed the effect: OR 1.3, 95% CI 0.7-2.3. 2) Vitamin B12 deficiency not associated with macrocytosis (OR 1.2 [95% CI 0.6-2.7]) and macrocytic anemia(OR 1.2 [95% CI 0.3-5.5]).
Automated hematology analyzer. Anemia(Hb women Hb <117 g/L, men Hb<134 g/L: prevalence 13%
Competitive protein binding assay. Vitamin B12 deficiency (B12<150 pmol/L, or increased tHcy (>15µmol/l) and low holoTC(<37 pmol/L)) n=97; No vitamin B12 deficiency (n=924)
Lietostudy; unselected population based health survey in Lieto, Finland. Data collected between March 1998 and December 1999.
≥65, 37% ≥75 1048 2007Loikas34 5 pointsUnclear: Prevalence of vitamin B12 deficiency 9% in anemic subjects and 5% in non-anemic subjects.
Manual cyanmethemoglobin method. Anemia(Hb<12 g/dL): prevalence 7.5% in men and 20% in women
Method using L. Leichmanii Vitamin B12 deficiency: vitamin B12 <140 pg/mL(103 pmol/L), prevalence = 5.4%
Random sample of people >65 years living at home in Kilsyth and Northern Glasgow, UK.
>653471973McLennan35 *Basedonchecklists fromvan der Windt et al.23;24
Quality of study*
Presence of an associationHemoglobin(Hb): analysis and limits for anemia
Vitamin B12 (VitB12): analysis and limits for deficiency
Study populationAge of subjects (years)
Sample size (N)Year of publicationAuthor
Appendix 3. Observational cross-sectional studies on etiologyof vitamin B12 deficiency and anemiain older subjects included in the present review
5 pointsNo: 1) No differences in vitamin B12 between anemicand non-anemic patients: mean vitamin B12 538 (SD 559) pg/mLvs523 (SD 393) pg/mL, p>0.05. 2) No difference in prevalence of vitamin B12 deficiency between anemicand non-anemic patients (11.3% vs4.9%, p>0.05)
Adviacell counter. Anemiawas defined as Hb<12 g/dL for women and Hb<13 g/dL for men. Prevalence: 10.5%
Radioimmunoanalysis. Vitamin B12 deficiency: vitamin B12 ≤270 pg/mL
All consecutive patients scheduled for major orthopedicsurgery for which blood was routinely grouped preoperatively in University Hospital in Barcelona, Spain. Data collected from January 2001 and December 2002.
Mean 68 (SD 13)5992009Bisbe38
5 pointsYes: 1) 3.2% anemiain subjects with normal vitamin B12; 8.3% anemiain subjects with low vitamin B12: adjusted OR 2.7 (95% CI 1.7-4.4) 2) Low vitamin B12 associated with macrocytosis(adjusted OR 1.8 [95% CI 1.02-3.1])
Hematologyflow cytometer. Anemia (women Hb<12 g/dL and men Hb<13 g/dL): prevalence 4.5%
Radioassay. Low vitamin B12 status: vitamin B12<148 pmol/L or MMA>210 nmol/L for serum vitamin B12-replete participants with normal creatinine concentrations: prevalence 25%
Non-institutionalizedcivilian population (NHANES), USA. Data collected from 1999-2002.
≥60, mean 70 (SEM 0.32)
1459 2007Morris36 4 pointsUnclear: 1) No difference in Ht between subjects with B12 deficiency (39.9 mg/dL (sd4.7)) and non- deficient subjects (39.9 mg/dL (sd4.2)). 2) Anemiamore common in vitamin B12 deficient subjects than in non-deficient subjects (17.4% vs. 11%, p=0.05). 3) No difference in between subjects with vitamin B12 deficiency and those without (93.5 fL, SD 7.5 vs93.9 fL, SD 6.5) Method not specified. Anemiawas defined as Ht<35 mg/dL.
Competitive protein binding assays. Vitamin B12 deficiency (serum vitamin B12 level <258 pmol/L, MMA level >271 nmol/L, MMA = 2- methylcitricacid level): prevalence 17.3%
Physically disabled older women living in the community (Women’s Health and Ageing Study), Baltimore area, USA
≥65, mean 77.3 7002000Penninx37 Hospitalized/Institutionalized *Basedonchecklists fromvan der Windt et al.23;24
Quality of study*
Presence of an associationHemoglobin(Hb): analysis and limits for anemia
Vitamin B12 (VitB12): analysis and limits for deficiency
Study populationAge of subjects (years)
Sample size (N)Year of publicationAuthor
Appendix 3. Observational cross-sectional studies on etiologyof vitamin B12 deficiency and anemiain older subjects included in the present review 5 pointsNo: 1) No differences in vitamin B12 between anemicand non-anemic patients: mean vitamin B12 538 (SD 559) pg/mLvs523 (SD 393) pg/mL, p>0.05. 2) No difference in prevalence of vitamin B12 deficiency between anemicand non-anemic patients (11.3% vs4.9%, p>0.05) Adviacell counter. Anemiawas defined as Hb<12 g/dL for women and Hb<13 g/dL for men. Prevalence: 10.5%
Radioimmunoanalysis. Vitamin B12 deficiency: vitamin B12 ≤270 pg/mL
All consecutive patients scheduled for major orthopedicsurgery for which blood was routinely grouped preoperatively in University Hospital in Barcelona, Spain. Data collected from January 2001 and December 2002.
Mean 68 (SD 13)5992009Bisbe38
5 pointsYes: 1) 3.2% anemiain subjects with normal vitamin B12; 8.3% anemiain subjects with low vitamin B12: adjusted OR 2.7 (95% CI 1.7-4.4) 2) Low vitamin B12 associated with macrocytosis(adjusted OR 1.8 [95% CI 1.02-3.1])
Hematologyflow cytometer. Anemia (women Hb<12 g/dL and men Hb<13 g/dL): prevalence 4.5%
Radioassay. Low vitamin B12 status: vitamin B12<148 pmol/L or MMA>210 nmol/L for serum vitamin B12-replete participants with normal creatinine concentrations: prevalence 25%
Non-institutionalizedcivilian population (NHANES), USA. Data collected from 1999-2002.
≥60, mean 70 (SEM 0.32)
1459 2007Morris36 4 pointsUnclear: 1) No difference in Ht between subjects with B12 deficiency (39.9 mg/dL (sd4.7)) and non- deficient subjects (39.9 mg/dL (sd4.2)). 2) Anemiamore common in vitamin B12 deficient subjects than in non-deficient subjects (17.4% vs. 11%, p=0.05). 3) No difference in between subjects with vitamin B12 deficiency and those without (93.5 fL, SD 7.5 vs93.9 fL, SD 6.5) Method not specified. Anemiawas defined as Ht<35 mg/dL.
Competitive protein binding assays. Vitamin B12 deficiency (serum vitamin B12 level <258 pmol/L, MMA level >271 nmol/L, MMA = 2- methylcitricacid level): prevalence 17.3%
Physically disabled older women living in the community (Women’s Health and Ageing Study), Baltimore area, USA
≥65, mean 77.3 7002000Penninx37 Hospitalized/Institutionalized *Basedonchecklists fromvan der Windt et al.23;24
Quality of study*
Presence of an associationHemoglobin(Hb): analysis and limits for anemia
Vitamin B12 (VitB12): analysis and limits for deficiency
Study populationAge of subjects (years)
Sample size (N)Year of publicationAuthor
Appendix 3. Observational cross-sectional studies on etiologyof vitamin B12 deficiency and anemiain older subjects included in the present review
5 pointsUnclear: 1) Mean Hb (SD) for normal vitamin B12: 13.0 g/dL (1.3); for possible vitamin B12 deficiency: 12.1 g/dL (1.0); for definite vitamin B12 deficiency: 12.4 g/dL (1.2) p=0.03. After adjustment for confounding variables no association between vitamin B12 and hematological indices. 2) Mean MCV (SD) for normal vitB12 status: 90.6 fL (9.6); for possible vitB12 deficiency: 88.8 fL (8.2); for definite B12 deficiency: 90.2 fL (9.0), NS.
Maxim Cell Count analyzer. Anemia: Hb<12 g/dL.
Solid phase no-boil Dual count radioimmunoassay. Definite vitamin B12 deficiency: vitamin B12<150 pmol/L and MMA>0.4 mmol/L (29.1%). Possible vitamin B12 deficiency: vitamin B12<150 pmol/L or MMA>0.4 mmol/L (46.9%)
Female ambulatory vegetarians (>3 years) in Hong Kong. >55, mean age >78.0962002Kwok41†
5 pointsNo: 1) 6.0% of subjects with anemia and 5.2% of subjects without anemiahad vitamin B12 <140 pmol/L, p<0.2. 2) 9.8% of subjects with macrocytosisand 4.6% of subjects with normocytosishad B12 <140 pmol/L, p<0.001
Method not specified. Anemia(women Hb<11.5 g/dL and men Hb<13 g/dL).
Microparticleenzyme intrinsic factor assay. Definite vitamin B12 deficiency: vitamin B12 level <140 pmol/L: prevalence 6.6%
All patients admitted to the Prince of Wales hospital, Hong Kong with vitamin B12 measurements in 1996.
48% >70 34532001Chui39 5 pointsUnclear: 1) Median (P5-P95) vitamin B12 for subjects with anemia282 (65-1218) pmol/L and for subjects without anemia237 (103-1476) pmol/L (Not significant). 2) Median Hb for subjects with vitamin B12<110 pmol/L 7.63 (4.84-8.94) mmol/L and for subjects with vitamin B12≥110 pmol/L 8.07 (5.46-9.81) mmol/L, p=0.04. 3) Median MCV for subjects with vitamin B12<110 pmol/L 95 (82-105) fL and for subjects with vitamin B12≥110 pmol/L 93 (80-104) fL, NS Coulter S plus IV. Anemia(Hb ≤7.14 mmol/L): N=80 (27%)
Radioassay. Low vitamin B12 levels (<110 pmol/L): N=22 (7.5%)
Consecutive patients admitted to the geriatric department of the University Hospital, Leuven, Belgium
>65 2921990Joosten40 *Basedonchecklists fromvan der Windt et al.23;24 †>51.1% of the study population lived in old age home residence
Quality of study*
Presence of an associationHemoglobin(Hb): analysis and limits for anemia
Vitamin B12 (VitB12): analysis and limits for deficiency
Study populationAge of subjects (years)
Sample size (N)Year of publicationAuthor
Appendix 3. Observational cross-sectional studies on etiologyof vitamin B12 deficiency and anemiain older subjects included in the present review 5 pointsUnclear: 1) Mean Hb (SD) for normal vitamin B12: 13.0 g/dL (1.3); for possible vitamin B12 deficiency: 12.1 g/dL (1.0); for definite vitamin B12 deficiency: 12.4 g/dL (1.2) p=0.03. After adjustment for confounding variables no association between vitamin B12 and hematological indices. 2) Mean MCV (SD) for normal vitB12 status: 90.6 fL (9.6); for possible vitB12 deficiency: 88.8 fL (8.2); for definite B12 deficiency: 90.2 fL (9.0), NS.
Maxim Cell Count analyzer. Anemia: Hb<12 g/dL.
Solid phase no-boil Dual count radioimmunoassay. Definite vitamin B12 deficiency: vitamin B12<150 pmol/L and MMA>0.4 mmol/L (29.1%). Possible vitamin B12 deficiency: vitamin B12<150 pmol/L or MMA>0.4 mmol/L (46.9%)
Female ambulatory vegetarians (>3 years) in Hong Kong. >55, mean age >78.0962002Kwok41†
5 pointsNo: 1) 6.0% of subjects with anemia and 5.2% of subjects without anemiahad vitamin B12 <140 pmol/L, p<0.2. 2) 9.8% of subjects with macrocytosisand 4.6% of subjects with normocytosishad B12 <140 pmol/L, p<0.001
Method not specified. Anemia(women Hb<11.5 g/dL and men Hb<13 g/dL).
Microparticleenzyme intrinsic factor assay. Definite vitamin B12 deficiency: vitamin B12 level <140 pmol/L: prevalence 6.6%
All patients admitted to the Prince of Wales hospital, Hong Kong with vitamin B12 measurements in 1996.
48% >70 34532001Chui39 5 pointsUnclear: 1) Median (P5-P95) vitamin B12 for subjects with anemia282 (65-1218) pmol/L and for subjects without anemia237 (103-1476) pmol/L (Not significant). 2) Median Hb for subjects with vitamin B12<110 pmol/L 7.63 (4.84-8.94) mmol/L and for subjects with vitamin B12≥110 pmol/L 8.07 (5.46-9.81) mmol/L, p=0.04. 3) Median MCV for subjects with vitamin B12<110 pmol/L 95 (82-105) fL and for subjects with vitamin B12≥110 pmol/L 93 (80-104) fL, NS Coulter S plus IV. Anemia(Hb ≤7.14 mmol/L): N=80 (27%)
Radioassay. Low vitamin B12 levels (<110 pmol/L): N=22 (7.5%)
Consecutive patients admitted to the geriatric department of the University Hospital, Leuven, Belgium
>65 2921990Joosten40 *Basedonchecklists fromvan der Windt et al.23;24 †>51.1% of the study population lived in old age home residence
Quality of study*
Presence of an associationHemoglobin(Hb): analysis and limits for anemia
Vitamin B12 (VitB12): analysis and limits for deficiency
Study populationAge of subjects (years)
Sample size (N)Year of publicationAuthor
Appendix 3. Observational cross-sectional studies on etiologyof vitamin B12 deficiency and anemiain older subjects included in the present review
3 pointsUnclear: 1) No statistically significant correlation between Hb and vitamin B12. 2) Tendency in females for vitamin B12 to decrease as Hb increased.
Modified cyanmethemoglobin method. Anemia(Hb<12 g/dL in women and Hb<13 g/dL in men): prevalence 15% (13% in women and 18.2% in men)
Radioimmunoassay. Vitamin B12 deficiency (vitamin B12 <200 pg/mL[148 pmol/L]): prevalence 6.9% (8.8% in women and 3.7%) in men)
Subjects visiting clinic for older individuals in RajvithiHospital, Bangkok
≥601471993Prayurahong44
2 pointsNo: 1) Mean Hb for cases 124.5 (SD 22.4) g/L and for controls 129.7 (SD 16.2) g/L, student t-test: p=0.251 2) Mean MCV for cases 95.6 (SD 9.2) fL and for controls 93.2 (SD 5.1) fL, student t-test: p=0.127
Method not specified. Reference range for women 115-160 g/L and for men 130-180 g/L.
Radioassay. Cases: vitamin B12<150 pmol/L Controls: vitamin B12150 pmol/L
Patients with suspected low vitamin B12 levels based on clinical examination by attending staff in Royal Melbourne and North West hospitals, Australia. If low vitamin B12: case. If normal vitamin B12: control.
Cases: mean 79.8 Controls: mean 80.7
Cases: 43, Controls: 51
1996Metz42 3 pointsNo: 1) No difference in prevalence low Hb between quintiles of vitamin B12 (Q1: 55%, Q2: 53%, Q3: 52%, Q4: 54% and Q5: 63%) or between groups of vitamin B12 status (frankly deficient: 54%, suboptimally deficient: 53%, possibly deficiency: 54%, and normal: 58%). 2) No difference in prevalence high MCV(>100fL) between groups of vitamin B12 status (frankly deficient: 10%, suboptimallydeficient: 12%, possibly deficiency: 7%, and normal: 9%).
Method not specified. Low Hb: <130 g/L for males and <115 g/L for females
Method not specified. Population divided in quintiles of vitamin B12, and stratified as frankly deficient (<200 ng/L [148 pmol/L]), suboptimallydeficient (200-249 ng/L [148- 184 pmol/L]), possibly deficient (250-349 ng/L [185-257 pmol/L]) and normal (>350 ng/L [258 pmol/l])
Hospitalized patients in Belfast, Ireland, who had vitamin B12, folate, Hb, MCV and ferritin measured within 4 days of each other in February-July 2003
65-85 9052004Mooney43† *Basedonchecklists fromvan der Windt et al.23;24 †Additional information in CuskellyGJ, Mooney KM, Young IS. Folate and vitamin B12: friendly or enemy nutrients for the elderly.Proc NutrSoc. 2007;66(4):548-558.
Quality of study*
Presence of an associationHemoglobin(Hb): analysis and limits for anemia
Vitamin B12 (VitB12): analysis and limits for deficiency
Study populationAge of subjects (years)
Sample size (N)Year of publicationAuthor
Appendix 3. Observational cross-sectional studies on etiologyof vitamin B12 deficiency and anemiain older subjects included in the present review 3 pointsUnclear: 1) No statistically significant correlation between Hb and vitamin B12. 2) Tendency in females for vitamin B12 to decrease as Hb increased.
Modified cyanmethemoglobin method. Anemia(Hb<12 g/dL in women and Hb<13 g/dL in men): prevalence 15% (13% in women and 18.2% in men)
Radioimmunoassay. Vitamin B12 deficiency (vitamin B12 <200 pg/mL[148 pmol/L]): prevalence 6.9% (8.8% in women and 3.7%) in men)
Subjects visiting clinic for older individuals in RajvithiHospital, Bangkok
≥601471993Prayurahong44
2 pointsNo: 1) Mean Hb for cases 124.5 (SD 22.4) g/L and for controls 129.7 (SD 16.2) g/L, student t-test: p=0.251 2) Mean MCV for cases 95.6 (SD 9.2) fL and for controls 93.2 (SD 5.1) fL, student t-test: p=0.127
Method not specified. Reference range for women 115-160 g/L and for men 130-180 g/L.
Radioassay. Cases: vitamin B12<150 pmol/L Controls: vitamin B12150 pmol/L
Patients with suspected low vitamin B12 levels based on clinical examination by attending staff in Royal Melbourne and North West hospitals, Australia. If low vitamin B12: case. If normal vitamin B12: control.
Cases: mean 79.8 Controls: mean 80.7
Cases: 43, Controls: 51
1996Metz42 3 pointsNo: 1) No difference in prevalence low Hb between quintiles of vitamin B12 (Q1: 55%, Q2: 53%, Q3: 52%, Q4: 54% and Q5: 63%) or between groups of vitamin B12 status (frankly deficient: 54%, suboptimally deficient: 53%, possibly deficiency: 54%, and normal: 58%). 2) No difference in prevalence high MCV(>100fL) between groups of vitamin B12 status (frankly deficient: 10%, suboptimallydeficient: 12%, possibly deficiency: 7%, and normal: 9%).
Method not specified. Low Hb: <130 g/L for males and <115 g/L for females
Method not specified. Population divided in quintiles of vitamin B12, and stratified as frankly deficient (<200 ng/L [148 pmol/L]), suboptimallydeficient (200-249 ng/L [148- 184 pmol/L]), possibly deficient (250-349 ng/L [185-257 pmol/L]) and normal (>350 ng/L [258 pmol/l])
Hospitalized patients in Belfast, Ireland, who had vitamin B12, folate, Hb, MCV and ferritin measured within 4 days of each other in February-July 2003
65-85 9052004Mooney43† *Basedonchecklists fromvan der Windt et al.23;24 †Additional information in CuskellyGJ, Mooney KM, Young IS. Folate and vitamin B12: friendly or enemy nutrients for the elderly.Proc NutrSoc. 2007;66(4):548-558.
Quality of study*
Presence of an associationHemoglobin(Hb): analysis and limits for anemia
Vitamin B12 (VitB12): analysis and limits for deficiency
Study populationAge of subjects (years)
Sample size (N)Year of publicationAuthor
Appendix 3. Observational cross-sectional studies on etiologyof vitamin B12 deficiency and anemiain older subjects included in the present review
5 pointsNo: 1) Mean Hb levels were not significantly reduced in those with low vitamin B12. Men; 140 (sd12) vs137 (sd22) g/L. Women: 128 (sd10) vs129 (sd 18) g/L (NS). 2) Those with low vitamin B12 had an elevated MCV compared to control subjects (96.0 [SD 6.7] fL vs91.7 [SD 6.0], p<0.001).
Coulter S plus IV methodRadiosorbentassay. Low vitamin B12 levels: <175 pmol/L + normal ferritin and folatelevels (N=37). Reference group: vitamin B12 >175 pmol/L, ferritin 100 ng/ml, erythrocyte folate75 ng/mLand no known chronic inflammatory disease (N=253)
Consecutive new referrals to a geriatric medical unit in Glasgow, Scotland.
Range 62- 110 2901997Stott45 4 pointsYes: 1) Vitamin B12 deficient patients had lower hemoglobin than patients with normal vitamin B12. 2) Vitamin B12 deficient patients had significantly higher MCV than patients with normal vitamin B12 levels (p<0.001).
Method not specified.Chemiluminescent microparticle immunoassay technology. Vitamin B12 deficiency: vitamin B12 <189 pg/mLand homocysteine concentrations >15mol/L. Prevalence 19.7%
Patients in the department of Neurology of Shanghai Punan Hospital, Shanghai, China, from March 2007 to July 2008.
Mean 77.1 (SD 7.5), range 60- 96
8272009Wang46 4 pointsNo: No correlation between vitamin B12 and hemoglobin.
Method not specified. Moderate anemia (Hb<11.5 g/dL), mild anemia(Hb 11.6-12.5 g/dL), normal Hb (>12.5 g/dL)
Method unknown. Low vitamin B12 levels: <180 ng/L (133 pmol/L)
Consecutive patients with chronic heart failure attending a heart failure clinic in Cottingham, UK
Mean 72.5 (10.3)2962004Witte47 *Basedonchecklists fromvan der Windt et al.23;24
Quality of study*
Presence of an associationHemoglobin(Hb): analysis and limits for anemia
Vitamin B12 (VitB12): analysis and limits for deficiency
Study populationAge of subjects (years)
Sample size (N)Year of publicationAuthor
Appendix 3. Observational cross-sectional studies on etiologyof vitamin B12 deficiency and anemiain older subjects included in the present review 5 pointsNo: 1) Mean Hb levels were not significantly reduced in those with low vitamin B12. Men; 140 (sd12) vs137 (sd22) g/L. Women: 128 (sd10) vs129 (sd 18) g/L (NS). 2) Those with low vitamin B12 had an elevated MCV compared to control subjects (96.0 [SD 6.7] fL vs91.7 [SD 6.0], p<0.001).
Coulter S plus IV methodRadiosorbentassay. Low vitamin B12 levels: <175 pmol/L + normal ferritin and folatelevels (N=37). Reference group: vitamin B12 >175 pmol/L, ferritin 100 ng/ml, erythrocyte folate75 ng/mLand no known chronic inflammatory disease (N=253)
Consecutive new referrals to a geriatric medical unit in Glasgow, Scotland.
Range 62- 110 2901997Stott45 4 pointsYes: 1) Vitamin B12 deficient patients had lower hemoglobin than patients with normal vitamin B12. 2) Vitamin B12 deficient patients had significantly higher MCV than patients with normal vitamin B12 levels (p<0.001).
Method not specified.Chemiluminescent microparticle immunoassay technology. Vitamin B12 deficiency: vitamin B12 <189 pg/mLand homocysteine concentrations >15mol/L. Prevalence 19.7%
Patients in the department of Neurology of Shanghai Punan Hospital, Shanghai, China, from March 2007 to July 2008.
Mean 77.1 (SD 7.5), range 60- 96
8272009Wang46 4 pointsNo: No correlation between vitamin B12 and hemoglobin.
Method not specified. Moderate anemia (Hb<11.5 g/dL), mild anemia(Hb 11.6-12.5 g/dL), normal Hb (>12.5 g/dL)
Method unknown. Low vitamin B12 levels: <180 ng/L (133 pmol/L)
Consecutive patients with chronic heart failure attending a heart failure clinic in Cottingham, UK
Mean 72.5 (10.3)2962004Witte47 *Basedonchecklists fromvan der Windt et al.23;24
Quality of study*
Presence of an associationHemoglobin(Hb): analysis and limits for anemia
Vitamin B12 (VitB12): analysis and limits for deficiency
Study populationAge of subjects (years)
Sample size (N)Year of publicationAuthor
Appendix 3. Observational cross-sectional studies on etiologyof vitamin B12 deficiency and anemiain older subjects included in the present review
n checklists from van derWindtet al.23;24 = 0 points 1 point han 50 participants was a requirement for inclusion in the review. Studies with more than 100 participants were rewarded with an additional point.
6 points4 points5 points4 points6 points6 points5 pointscore
YesYesYesYesYesYesYesore than 100 subjects included in the study*
YesNoYesNoYesYesNothe results adjusted for possible confounders?
is
NoNo YesNoYesNoNonly new and incident patients used?
YesYesYesYesYesYesYese outcome measured with a valid and reproducible ?
me assessment
YesYesYesYesYesYesYese exposure measured with a valid and reproducible ?
ure assessment
Yes?No?NoYesYesore than 80% of the eligible subjects participate in the
YesYesNoYesYes;YesYes alid selection criteria used for the study population?
ulation
Arch Intern MedAm J ClinNutrJ Intern MedAge AgeingBr J NutrJ Intern MedCent AfrJ Medl
2009200320052006200820011997
Lippi33Johnson32Hvas31Hin30Clarke29Björkegren28Allain27x 4.Quality assessment of cross-sectional observational studies on etiologyof vitamin B12 deficiency and anemiain elderly subjects included in the present review n checklists from van derWindtet al.23;24 = 0 points 1 point han 50 participants was a requirement for inclusion in the review. Studies with more than 100 participants were rewarded with an additional point.
6 points4 points5 points4 points6 points6 points5 pointscore
YesYesYesYesYesYesYesore than 100 subjects included in the study*
YesNoYesNoYesYesNothe results adjusted for possible confounders?
is
NoNo YesNoYesNoNonly new and incident patients used?
YesYesYesYesYesYesYese outcome measured with a valid and reproducible ?
me assessment
YesYesYesYesYesYesYese exposure measured with a valid and reproducible ?
ure assessment
Yes?No?NoYesYesore than 80% of the eligible subjects participate in the
YesYesNoYesYes;YesYes alid selection criteria used for the study population?
ulation
Arch Intern MedAm J ClinNutrJ Intern MedAge AgeingBr J NutrJ Intern MedCent AfrJ Medl
2009200320052006200820011997
Lippi33Johnson32Hvas31Hin30Clarke29Björkegren28Allain27x 4.Quality assessment of cross-sectional observational studies on etiologyof vitamin B12 deficiency and anemiain elderly subjects included in the present review
ists from van derWindtet al.23;24 ts articipants was a requirement for inclusion in the review. Studies with more than 100 participants were rewarded with an additional point.
5 points5 points5 points4 points5 points5 points6 points
YesYesYesYesYesYesYes 100 subjects included in the study*
NoNoNoNoYesNoYes adjusted for possible confounders?
NoNoNoNoNoYesYes and incident patients used?
YesYesYesYes YesYesYese measured with a valid and reproducible
ment
YesYesYesYesYes YesYese measured with a valid and reproducible
ent
YesYesYesNo? NoNo% of the eligible subjects participate in the
YesYesYesYesYesYesYestion criteria used for the study population?
n
Ned TijdschrGeneeskdNutritionTransfusAlternTransfusMedAm J PsychiatryAm J ClinNutrQ J MedAge Ageing
1990200120082000200719732007
Joosten40Chui39Bisbe38Penninx37Morris36McLennan35Loikas34
uality assessment of cross-sectional observational studies on etiologyof vitamin B12 deficiency and anemiain elderly subjects included in the present review ists from van derWindtet al.23;24 ts articipants was a requirement for inclusion in the review. Studies with more than 100 participants were rewarded with an additional point.
5 points5 points5 points4 points5 points5 points6 points
YesYesYesYesYesYesYes 100 subjects included in the study*
NoNoNoNoYesNoYes adjusted for possible confounders?
NoNoNoNoNoYesYes and incident patients used?
YesYesYesYes YesYesYese measured with a valid and reproducible
ment
YesYesYesYesYes YesYese measured with a valid and reproducible
ent
YesYesYesNo? NoNo% of the eligible subjects participate in the
YesYesYesYesYesYesYestion criteria used for the study population?
n
Ned TijdschrGeneeskdNutritionTransfusAlternTransfusMedAm J PsychiatryAm J ClinNutrQ J MedAge Ageing
1990200120082000200719732007
Joosten40Chui39Bisbe38Penninx37Morris36McLennan35Loikas34
uality assessment of cross-sectional observational studies on etiologyof vitamin B12 deficiency and anemiain elderly subjects included in the present review
on checklists from van derWindtet al.23;24 = 0 points 1 point han 50 participants was a requirement for inclusion in thereview. Studies with more than 100 participants were rewarded with an additional point. nal information in CuskellyGJ, Mooney KM, Young IS. Folate and vitamin B12: friendly or enemy nutrients for the elderly.Proc NutrSoc. 2007;66(4):548-558.
4 points4 points5 points3 points3 points2 points5 pointscore
YesYesYesYesYesNoNoore than 100 subjects included in the study*
NoNoNoNoNoNoYesthe results adjusted for possible confounders?
is
No?No???Yesly new and incident patients used?
YesYesYes YesYesYesYese outcome measured with a valid and reproducible d?
e assessment
?YesYesYesYesYesYese exposure measured with a valid and reproducible d?
re assessment
Yes?Yes? ???ore than 80% of the eligible subjects participate in the
YesYesYes? ?NoYesalid selection criteria used for the study population?
lation
Am Heart JNeuroscience BullBr J NutrJ Med Assoc ThaiProc NutrSocJ Am GeriatrSocAm J Hematoll
2004200919971993200419962002
Witte47Wang46Stott45Prayurahong44Mooney43†Metz42Kwok41x 4.Quality assessment of cross-sectional observational studies on etiologyof vitamin B12 deficiency and anemiain elderly subjects included in the present review on checklists from van derWindtet al.23;24 = 0 points 1 point han 50 participants was a requirement for inclusion in thereview. Studies with more than 100 participants were rewarded with an additional point. nal information in CuskellyGJ, Mooney KM, Young IS. Folate and vitamin B12: friendly or enemy nutrients for the elderly.Proc NutrSoc. 2007;66(4):548-558.
4 points4 points5 points3 points3 points2 points5 pointscore
YesYesYesYesYesNoNoore than 100 subjects included in the study*
NoNoNoNoNoNoYesthe results adjusted for possible confounders?
is
No?No???Yesly new and incident patients used?
YesYesYes YesYesYesYese outcome measured with a valid and reproducible d?
e assessment
?YesYesYesYesYesYese exposure measured with a valid and reproducible d?
re assessment
Yes?Yes? ???ore than 80% of the eligible subjects participate in the
YesYesYes? ?NoYesalid selection criteria used for the study population?
lation
Am Heart JNeuroscience BullBr J NutrJ Med Assoc ThaiProc NutrSocJ Am GeriatrSocAm J Hematoll
2004200919971993200419962002
Witte47Wang46Stott45Prayurahong44Mooney43†Metz42Kwok41x 4.Quality assessment of cross-sectional observational studies on etiologyof vitamin B12 deficiency and anemiain elderly subjects included in the present review
ecklists fromvan der Windt et al.23,24 dependent assessment by DAWM van derWindt 7 pointsNo: 1) Vitamin B12 deficiency was not associated with the presence of anemiaat baseline (adjusted OR 1.51 95% CI 0.79-2.87), nor with developing anemiaduring follow-up (adjusted HR 0.92 95% CI 0.46-1.82). 2) At baseline, median MCV was higher in those with low vitamin B12 than in those with normal vitamin B12 (93 fL (IQR 90-96) and 91 fL (IQR 88-94), respectively). There were no differences in the changes in MCV during follow-up (p=0.77).
Automated analysis system. Anemia: Hb<12 g/dL for women and Hb<13 g/dL for men.
Dual Count Solid Phase No Boil Assay. Vitamin B12 deficiency: <150 pmol/L: prevalence 16.1%
All 85-year-old inhabitants of Leiden, the Netherlands. Participants using vitamin B12 or folate supplements at baseline or during follow-up were excluded. Participants were enrolled between September 1997 and September 1999.
85 4232008
Quality of study*†Presence of an associationHemoglobin(Hb): analysis and limits for anemiaVitamin B12 (VitB12): analysis and limits for deficiency
Study populationAge of subjects (years)
Sample size (N)Year of publication
Observational longitudinal study on etiologyof vitamin B12 deficiency and anemiain older subjects included in the present review ecklists fromvan der Windt et al.23,24 dependent assessment by DAWM van derWindt 7 pointsNo: 1) Vitamin B12 deficiency was not associated with the presence of anemiaat baseline (adjusted OR 1.51 95% CI 0.79-2.87), nor with developing anemiaduring follow-up (adjusted HR 0.92 95% CI 0.46-1.82). 2) At baseline, median MCV was higher in those with low vitamin B12 than in those with normal vitamin B12 (93 fL (IQR 90-96) and 91 fL (IQR 88-94), respectively). There were no differences in the changes in MCV during follow-up (p=0.77).
Automated analysis system. Anemia: Hb<12 g/dL for women and Hb<13 g/dL for men.
Dual Count Solid Phase No Boil Assay. Vitamin B12 deficiency: <150 pmol/L: prevalence 16.1%
All 85-year-old inhabitants of Leiden, the Netherlands. Participants using vitamin B12 or folate supplements at baseline or during follow-up were excluded. Participants were enrolled between September 1997 and September 1999.
85 4232008
Quality of study*†Presence of an associationHemoglobin(Hb): analysis and limits for anemiaVitamin B12 (VitB12): analysis and limits for deficiency
Study populationAge of subjects (years)
Sample size (N)Year of publication
Observational longitudinal study on etiologyof vitamin B12 deficiency and anemiain older subjects included in the present review
Based on chec No or ? = 0 po Yes = 1 point *more than 50 more than 100
Total score
Were more tha
Were the resul
Analysis
Were data coll
Were only ne
Was the outcom
Outcome asse
Was the expos
Exposure asse
Was the respo
Did more than
Were valid sel
Study populati
Journal
Year
Author
Appendix 6. Q vitamin B12 d klists from van derWindtet al.23,24 ints participants was a requirement for inclusion in the review. Studies with participants were rewarded with an additional point.
7 points
Yesn 100 subjects included in the study*
Yests adjusted for possible confounders?
Yesected for ≥1 year?
?w and incident patients used?
Yese measured with a valid and reproducible method?
ssment
Yesure measured with a valid and reproducible method?
ssment
?nse at main moment of follow up >80
Yes 80% of the eligible subjects participate in the study?
Yesection criteria used for the study population?
on
Arch Intern Med
2008
Den Elzen48
uality assessment of longitudinal observational studies on etiologyof eficiency and anemiain elderly subjects included in the present review Based on chec No or ? = 0 po Yes = 1 point *more than 50 more than 100
Total score
Were more tha
Were the resul
Analysis
Were data coll
Were only ne
Was the outcom
Outcome asse
Was the expos
Exposure asse
Was the respo
Did more than
Were valid sel
Study populati
Journal
Year
Author
Appendix 6. Q vitamin B12 d klists from van derWindtet al.23,24 ints participants was a requirement for inclusion in the review. Studies with participants were rewarded with an additional point.
7 points
Yesn 100 subjects included in the study*
Yests adjusted for possible confounders?
Yesected for ≥1 year?
?w and incident patients used?
Yese measured with a valid and reproducible method?
ssment
Yesure measured with a valid and reproducible method?
ssment
?nse at main moment of follow up >80
Yes 80% of the eligible subjects participate in the study?
Yesection criteria used for the study population?
on
Arch Intern Med
2008
Den Elzen48
uality assessment of longitudinal observational studies on etiologyof eficiency and anemiain elderly subjects included in the present review
klist from Jadadet al.25
2 pointsNo: 1) Mean change in Hb in g/L (SD) from baseline: Placebo: 2.3 (9.3), 10 g: 3.3 (9.8), 50 g: 0.7 (13.5) One-way ANOVA p=0.875 2) Mean change in MCV in fL (SD) from baseline: Placebo: 0.5 (1.3), 10 g: 1.4 (2.2), 50 g: 0.6 (1.1) One-way ANOVA p=0.421
Difference in change in Hb from baseline after 4 weeks (range 27-39 days)
Placebo (Australian Pharmaceutical Formulary (APF) red mixture and APF hydrobenzoate compound), 10 g oral cyanocobalaminor 50 g oral cyanocobalamindaily for 4 weeks
31 patients in two geriatric hospitals in Melbourne, Australia with subnormal serum vitamin B12 (100-150 pmol/L) discovered as part of their clinical assessment. Exclusion criteria: known neoplasm, life-threatening or terminal illness, history of malabsorption, pernicious anemia, anemiaof other cause, prior vitamin B12 treatment or vitamin supplementation, neurological disorder other than stroke.
Mean age placebo 78, vitamin B12 10 g 82, vitamin B12 50 g 85
Placebo n=11, oral vitamin B12 10 g n=10, oral vitamin B12 50 g, n=10
2002
4 pointsNo: 1) Hb change (%) in treatment group 1% and in placebo group 1%, p=0.95 (Student t-test). 2) MCV change (%) in treatment group 0% and in placebo group 0%, p=0.70 (Student t-test).
Percentage change in Hb levels after 3 months.
Weekly intramuscular injections of 1 mg cyanocobalamin(n=70) or placebo containing 1 mL of isotonic sodium chloride (n=70) for 1 month
140 subjects in Aarhus, Denmark, with elevated methylmalonicacid (P-MMA, 0.40-2.00 μmol/L) which had not received prior vitamin B12 treatment. Participants were enrolled between November 1998 and March 2000. Exclusion criteria: low Hb levels, low ferritin levels, TSH≥4.1 mIU/L, high creatinine levels, life- threatening disease, treatment with anticoagulants, tropical atoxicneuropathy.
Treatmen t group: Median 75 (range 19-92) Placebo group: 74 (range 33-88)
Placebo n=70, treatment n=70
2001
4 pointsNo: On average, a small decrease in Hb level but the difference between the mean change in both groups was small and not statistically significant (0.01 +/- 0.35 g)
Between-group differences in change in Hb in 5 weeks from baseline.
Intramuscular hydroxocobalamin (1000μg), twice in the first week, and then at weekly intervals for a further four weeks or placebo containing a matching solution of phenol red (phenylsulphonphtalein 0.075%)
Random sample of subjects aged ≥65 years from general practices in a town in Wales, UK. Subjects with vitamin B12 level <150 pg/mLwere invited to the trial. None had anemiaor evidence of vitamin B12 neuropathy and none was taking drugs that might interfere with vitamin B12 assays or anticonvulsants that might reduce the serum vitamin B12 level.
≥65Placebo n=19, Treatment n=20
1970
Quality*Treatment effectivenessOutcome measureInterventionStudy populationAge (years)Sample size (N)Year of publicatio n
andomized placebo-controlled trials of the effect of vitamin B12 administration onhemoglobinlevels in older subjects included in the present review klist from Jadadet al.25
2 pointsNo: 1) Mean change in Hb in g/L (SD) from baseline: Placebo: 2.3 (9.3), 10 g: 3.3 (9.8), 50 g: 0.7 (13.5) One-way ANOVA p=0.875 2) Mean change in MCV in fL (SD) from baseline: Placebo: 0.5 (1.3), 10 g: 1.4 (2.2), 50 g: 0.6 (1.1) One-way ANOVA p=0.421
Difference in change in Hb from baseline after 4 weeks (range 27-39 days)
Placebo (Australian Pharmaceutical Formulary (APF) red mixture and APF hydrobenzoate compound), 10 g oral cyanocobalaminor 50 g oral cyanocobalamindaily for 4 weeks
31 patients in two geriatric hospitals in Melbourne, Australia with subnormal serum vitamin B12 (100-150 pmol/L) discovered as part of their clinical assessment. Exclusion criteria: known neoplasm, life-threatening or terminal illness, history of malabsorption, pernicious anemia, anemiaof other cause, prior vitamin B12 treatment or vitamin supplementation, neurological disorder other than stroke.
Mean age placebo 78, vitamin B12 10 g 82, vitamin B12 50 g 85
Placebo n=11, oral vitamin B12 10 g n=10, oral vitamin B12 50 g, n=10
2002
4 pointsNo: 1) Hb change (%) in treatment group 1% and in placebo group 1%, p=0.95 (Student t-test). 2) MCV change (%) in treatment group 0% and in placebo group 0%, p=0.70 (Student t-test).
Percentage change in Hb levels after 3 months.
Weekly intramuscular injections of 1 mg cyanocobalamin(n=70) or placebo containing 1 mL of isotonic sodium chloride (n=70) for 1 month
140 subjects in Aarhus, Denmark, with elevated methylmalonicacid (P-MMA, 0.40-2.00 μmol/L) which had not received prior vitamin B12 treatment. Participants were enrolled between November 1998 and March 2000. Exclusion criteria: low Hb levels, low ferritin levels, TSH≥4.1 mIU/L, high creatinine levels, life- threatening disease, treatment with anticoagulants, tropical atoxicneuropathy.
Treatmen t group: Median 75 (range 19-92) Placebo group: 74 (range 33-88)
Placebo n=70, treatment n=70
2001
4 pointsNo: On average, a small decrease in Hb level but the difference between the mean change in both groups was small and not statistically significant (0.01 +/- 0.35 g)
Between-group differences in change in Hb in 5 weeks from baseline.
Intramuscular hydroxocobalamin (1000μg), twice in the first week, and then at weekly intervals for a further four weeks or placebo containing a matching solution of phenol red (phenylsulphonphtalein 0.075%)
Random sample of subjects aged ≥65 years from general practices in a town in Wales, UK. Subjects with vitamin B12 level <150 pg/mLwere invited to the trial. None had anemiaor evidence of vitamin B12 neuropathy and none was taking drugs that might interfere with vitamin B12 assays or anticonvulsants that might reduce the serum vitamin B12 level.
≥65Placebo n=19, Treatment n=20
1970
Quality*Treatment effectivenessOutcome measureInterventionStudy populationAge (years)Sample size (N)Year of publicatio n
andomized placebo-controlled trials of the effect of vitamin B12 administration onhemoglobinlevels in older subjects included in the present review
as ed on ch ec kl is t f rom J ad ad et al .
252 po in ts 4 po in ts 4 po in ts ta l s co re
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No ; 0 p oi nts N o; 0 po in ts N o; 0 po int s e m et hod t o ge ne ra te th e se qu en ce of r an dom iz at io n w as sc ri bed a nd i t w as i napp ro pr ia te
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No ; 0 p oi nts Y es; 1 p oin t Ye s; 1 p oi nt m et ho d o f do ubl e bl in di ng w as de sc ri be d a nd it w as pro pr ia te .
No ; 0 p oi nts Ye s; 1 p oi nt N o; 0 po int s e m et hod t o ge ne ra te th e se qu en ce of r an dom iz at io n w as sc ri bed a nd i t w as app ro pr iat e
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No ; 0 p oi nts N o; 0 po in ts Ye s; 1 p oi nt W as th er e a de sc ri pt io n o f w it hdr aw al s and d ro po ut s?
Ye s; 1 p oi nt Ye s; 1 p oi nt Ye s; 1 p oi nt W as t he st ud y desc ri be d as do ubl e bl ind?
Ye s; 1 p oi nt Ye s; 1 p oi nt Ye s; 1 p oi nt W as t he st ud y desc ri be d as r ando m iz ed?
J A m G er ia tr S oc C lin C hem BM J ur na l
2002 2001 1970 ear
Seal
51Hva s
50Hu gh es
49th or
x8.
Q ual it y a ss es sm en t of r and om iz ed pl ac eb o- co nt ro ll ed tr ia ls on th e e ff ect of vi ta m in B 12 a dm in is tr at ion on he m ogl ob in le ve ls in el de rl y sub jec ts in cl ude d in th e pr ese nt r ev iew as ed on ch ec kl is t f rom J ad ad et al .
252 po in ts 4 po in ts 4 po in ts ta l s co re
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No ; 0 p oi nts N o; 0 po int s N o; 0 po int s m et ho d o f do ubl e bl in di ng w as de sc ri be d a nd it w as ap pr op ri at e.
No ; 0 p oi nts N o; 0 po in ts N o; 0 po int s e m et hod t o ge ne ra te th e se qu en ce of r an dom iz at io n w as sc ri bed a nd i t w as i napp ro pr ia te
educ t 1 po in t i f
0 po int s 2 po in ts 1 po in t
No ; 0 p oi nts Y es; 1 p oin t Ye s; 1 p oi nt m et ho d o f do ubl e bl in di ng w as de sc ri be d a nd it w as pro pr ia te .
No ; 0 p oi nts Ye s; 1 p oi nt N o; 0 po int s e m et hod t o ge ne ra te th e se qu en ce of r an dom iz at io n w as sc ri bed a nd i t w as app ro pr iat e
dd 1 po in t i f
2 po in ts 2 po in ts 3 po in ts ot al
No ; 0 p oi nts N o; 0 po in ts Ye s; 1 p oi nt W as th er e a de sc ri pt io n o f w it hdr aw al s and d ro po ut s?
Ye s; 1 p oi nt Ye s; 1 p oi nt Ye s; 1 p oi nt W as t he st ud y desc ri be d as do ubl e bl ind?
Ye s; 1 p oi nt Ye s; 1 p oi nt Ye s; 1 p oi nt W as t he st ud y desc ri be d as r ando m iz ed?
J A m G er ia tr S oc C lin C hem BM J ur na l
2002 2001 1970 ear
Seal
51Hva s
50Hu gh es
49th or
x8.
