Table 1.

Long-term studies of effects of PPIs on vitamin B12 (VB12)

Year Study	Number. Pts(Pt)	Type Patient	Type Study	Study Design	Results	Ref
2010	17 (long-term PPI)/19 (no PPI)	Age 60–80 yrs Long-term care	Prospective	Baseline VB12, MMA levels and after 8 wk treatment with VB12 nasal spray in PPI users	1. At baseline long-term PPI users had lower VB12, Inc MMA and inc % VB12 deficiency (75% vs. 11%, p=0.006). 2. Nasal V12 spray Inc VB12, dec VB12 deficiency	[•32]
2008	659 141 PPIs, 150 H2R, 271 neither, over 72 mo time (Ave=18 mos)	Pts (age 60– 102 yrs)- Long-term care and community	Cross sectional sample	Serum VB12, demographics, VB12 history, multivitamin use	1. H2R usage did not influence VB12 levels but PPIs users had lower levels (p=0<0.00005). 2. Oral VB12 slowed but did not prevent decrease in VB12 levels 3. VB12 status low/marginal in 20% nursing home and 29% community elderly patients.	[33]
2008	125 long-term (>3yrs) PPI uses, 125 partners (non PPI users)	Aged ≥ 65 yrs	Cross sectional sample	Serum VB12, homocysteine levels (HCY), MCV	1. No difference in VB12 levels for PPI users, nonusers 2.3% of users and 2% nonusers had low VB12 levels 3. No difference in HCY levels or mean MCV.	[21]
2008	61 acid hypersecretors (46 ZES,15 other) taking PPIs	Acid hypersecretors (BAO>15 mEq/hr)	Longitudin al study	Yearly VB12 levels, 41 pts HCY and MMA levels determined) (in	1. 10% had low VB12 levels without signs VB12 deficiency 2.31% normal VB12 levels but inc MMA/HCY with normal folate levels 3. Concluded acid dec not explain VB12 deficiency.	[34]
2004	53 VB12 deficient pts compared to 212 controls for H2R/PPI use	Aged ≥ 65 yrs	Case control study	Control for age, gender. Multivitamin use, HP infection rate, compare chronic current use of H2R/PPIs	1. Chronic current use of PPIs/H2R’s associated inc VB12 deficiency (OR 4.45) 2. No association with short-term or past H2R/PPI use found 3. Suggest Chronic use H2R/PPI associated with higher VB12 deficiency.	[22]
2003	125 pts requiring VB12 supplementation compared to 500 controls	State-wide Medicaid population (109,444 pts)	Case control study	Controls matched for age, gender.	1. 18% of VB12 supplemented patients exposed to chronic acid suppression (>12 mos PPI/H2R0 compared to 11% of control group (p=0.025) 2. Conclude initiation of VB12 treatment is associated with chronic gastric acid suppressive therapy	[41]

Abbreviations. PPI-proton pump inhibitor; H2R-Histamine H2-receptor antagonist; wk-weeks; mo-month; yr-year; MMA-methylmalonic acid, HCY-homocysteine, MCV-mean corpuscular volume; Ave –average; inc-increase; dec-decrease