title: Methylmalonic Acid and Homocysteine as Indicators of Vitamin B-12 Deficiency in Cancer.
abstract: OBJECTIVE
  Normal or high serum vitamin B-12 levels can sometimes be seen in a B-12 deficient state, and can therefore be misleading. High levels of Methymalonic Acid (MMA) and Homocysteine (HC) have been identified as better indicators of B-12 deficiency than the actual serum B-12 level itself. We evaluated the prevalence of vitamin B-12 deficiency using appropriate cut-off levels of vitamin B-12, MMA and HC, and determined the relationship between serum levels of vitamin B-12, MMA and HC in cancer.
  
  
  METHODS
  This is a cross-sectional study using a consecutive case series of 316 cancer patients first seen at Cancer Treatment Centers of America® (CTCA) at Midwestern Regional Medical Center between April 2014 and June 2014. All patients were evaluated at baseline for vitamin B-12 (pg/mL), MMA (nmol/L) and HC (μmol/L) levels. In accordance with previously published research, the following cut-offs were used to define vitamin B-12 deficiency: <300 pg/mL for vitamin B-12, >260 nmol/L for MMA and >12 μmol/L for HC. The relationship between B-12, MMA and HC was evaluated using Spearman's rho correlation coefficient and cross-tabulation analysis. Receiver Operating Characteristic (ROC) curves were estimated using the non-parametric method to further evaluate the diagnostic accuracy of vitamin B-12 using Fedosov quotient as the "gold standard".
  
  
  RESULTS
  Mean age at presentation was 52.5 years. 134 (42.4%) patients were males while 182 (57.6%) were females. Median vitamin B-12, MMA and HC levels were 582.5 pg/mL, 146.5 nmol/L and 8.4 μmol/L respectively. Of 316 patients, 28 (8.9%) were vitamin B-12 deficient based on vitamin B-12 (<300 pg/mL), 34 (10.8%) were deficient based on MMA (>260 nmol/L) while 55 (17.4%) were deficient based on HC (>12 μmol/L). Correlation analysis revealed a significant weak negative correlation between vitamin B-12 and MMA (rho = -0.22) as well as B-12 and HC (rho = -0.35). ROC curves suggested MMA to have the best discriminatory power in predicting B-12 deficiency.
  
  
  CONCLUSIONS
  Vitamin B-12 is poorly correlated with MMA and HC in cancer. Using serum vitamin B-12 alone to evaluate B-12 status in cancer may fail to identify those with functional deficiency. A thorough clinical assessment is important to identify patients that may have risk factors and/or symptoms suggestive of deficiency. These patients should have additional testing of MMA and HC regardless of their B-12 levels.
authors.affiliation: Cancer Treatment Centers of America® (CTCA) at Midwestern Regional Medical Center, 2520 Elisha Ave, Zion, Illinois, 60099, United States of America.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Vashi
authors.affiliation: Cancer Treatment Centers of America® (CTCA) at Midwestern Regional Medical Center, 2520 Elisha Ave, Zion, Illinois, 60099, United States of America.
authors.forename: Persis
authors.initials: P
authors.lastname: Edwin
authors.affiliation: Cancer Treatment Centers of America® (CTCA) at Midwestern Regional Medical Center, 2520 Elisha Ave, Zion, Illinois, 60099, United States of America.
authors.forename: Brenten
authors.initials: B
authors.lastname: Popiel
authors.affiliation: Cancer Treatment Centers of America® (CTCA) at Midwestern Regional Medical Center, 2520 Elisha Ave, Zion, Illinois, 60099, United States of America.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Lammersfeld
authors.affiliation: Cancer Treatment Centers of America® (CTCA) at Midwestern Regional Medical Center, 2520 Elisha Ave, Zion, Illinois, 60099, United States of America.
authors.forename: Digant
authors.initials: D
authors.lastname: Gupta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D008764:Methylmalonic Acid / Q000097:blood*; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000150:complications; D015995:Prevalence; D014806:Vitamin B 12 Deficiency / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000453:epidemiology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006710:Homocysteine; D008764:Methylmalonic Acid