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"If you're interested in personal health, public health, or you just want to read an amazing story, I highly recommend this book."

Dr. Eric Norman

uMMA TEST: The Choice Over Other Tests

Serum b12 Assay

Falsely positive serum B12 tests (low levels in the absence of B12 deficiency)
Study shows assay to have only a 22.2% positive predictive value. After a five-year follow up on low serum B12 levels nearly 4 of 5 individuals were without clinical evidence of B12 deficiency.17,18

Of 504 patients with low serum B12, only 22% (109) had clinically important deficiency.26

Of 47 subjects with low serum B12 only 7 (15%) were shown to be clinically B12 deficient.17,18

About 20-40% of elderly people with low serum vitamin B12 levels have completely normal metabolic status 1,2 and cannot be regarded as B12 deficient.

"Because low cobalamin concentrations can occur in the absence of deficiency, the term 'cobalamin deficiency' should probably be reserved for those cases with accompanying clinical or metabolic evidence supporting the diagnosis". 2

For clarification, there is an inexact relationship between serum B12 and cellular B12 since the total serum B12 is bound to three carriers proteins: transcobalamin-I (TC-I),TC II and TC III. Only TC-II, which carries less than 20% of the serum B12, delivers B12 to the tissues. Measurement of TC-II levels have not been proven to be an accurate indicator of tissue B12 deficiency 6 and the assay is not a functional test.
Falsely negative serum B12 tests (normal levels in the presence of B12 deficiency)
Of 35 seniors with high uMMA, 49% had a normal serum B12 level.14

Subjects (14%) found B12 deficient showed equal numbers with serum B12 < 200 pg/ml (below normal) and between 200 and 300 pg/ml.27 Accordingly, MMA testing was recommended for individuals with serum B12 levels < 350 pg/ml .28 However, another study advised against serum MMA (SMMA) testing subjects with low normal serum B12 since huge numbers of non B12 deficient individuals would be caught in the net.2 This dilemma illustrates the need to use the accurate uMMA test.

Of 23 vegetarians identified with high uMMA, 83% (19/23) had normal serum B12 levels.5

Asymptomatic patients and healthy volunteers with normal B12 levels but elevated MMA have been reported. 1,2,5,14,27-32

Five geriatric patients with normal serum B12 levels and suspected Alzheimer's dementia, were reported successfully reversed with intramuscular B12. The lower limit of vitamin B12 in Japan and some European countries is 500 pg/mL, which is based on neurological criteria.32

Serum MMA test

Falsely positive serum MMA tests
Norman and Cronin documented reports of the SMMA assay yielding falsely positive results in conditions of renal insufficiency, thyroid disease, pregnancy, small bowel bacterial overgrowth, hemoconcentration, and for unexplained reasons.33

Renal insufficiency was associate with 25.5% of all abnormal SMMA levels in one survey of 725 individuals over age 60. Carmel et. al2 recommend renal insufficiency must be considered in evaluation high SMMA levels.

A study concludes that plasma creatinine must be included when assessing SMMA levels, even within the normal range.34
Falsely negative serum MMA tests
The serum MMA test was found less sensitive than the urinary MMA assay. In a study of suspected B12 deficient vegetarians, the SMMA test (normal = 73-271 nm/L) identified 5 of 8 (63%) whereas the uMMA (normal < 4.0) assay detected 7 of 8 (88%). uMMA levels normalized with B12 therapy but not all SMMA levels. Serum B12 levels supported the uMMA test as being valid .20 Although the numbers are small, this article indicates that if large numbers of individuals are tested, many individuals with neurologic manifestations may be missed without using the uMMA assay.

Serum Homocysteine

Published data show that serum Hcys levels are rarely, if ever, needed in addition to MMA levels to diagnose B12 deficiency. Reevaluating published data that listed both SMMA and Hcys using the current normal value for SMMA, of 37 B12 deficient patients, all were identified with high SMMA levels.22 Of 78 patients reported B12 deficient using SMMA and Hcys, 77 were identified by high SMMA The remaining patient with high serum Hcys was folate deficient, which could account for the high Hcys level.35

In an uMMA screening study, serum Hcys levels were above normal in only 9 of 16 subjects (14). SMMA rose in gastrectomized rats within two months after surgery whereas Hcys did not become elevated until ten months after surgery 36 and rats feed a B12 deficient diet showed elevated SMMA after 3 months but normal Hcys after 7 months.37 In nine vegetarians with high uMMA and /or low serum B12 levels, all had normal Hcys levels (Normal = 5.1-13.9 mol/L).20 Serum Hcys levels are also elevated by folate deficiency as well as numerous other conditions.6

Schilling Test

Falsely normal
The Schilling test can be falsely normal in individuals who are unable to absorb food-bound vitamin B12 but can absorb crystalline B12.38

uMMA Test

Falsely positive
In a double blinded prospective clinical evaluation of the uMMA test, the assay was reported to have a specificity of 99%.17 However, the one patient reported to have falsely high uMMA of 9.5 (normal <5.0) did not have a follow up uMMA test after B12 therapy and therefore was most likely tissue deficient without overt clinical evidence.

Of 16 subjects with elevated uMMA, all had normal MMA after B12 IM. (p<.001).14

Of 7 subjects with high uMMA all normalized with B12 therapy.20 Other studies noting high uMMA 5,9-11,39,40 demonstrate reductions of MMA with effective therapy and no problem with falsely high uMMA.
Falsely negative
The uMMA test identified non-anemic elderly individuals 14 and asymptomatic vegetarians 5 as B12 deficient. uMMA normalized with adequate B12 therapy. Normal serum B12 was found in 49% of the non-anemic elderly (normal uMMA < 5.0) and 83% of the vegetarian population. (normal uMMA < 4.0). These individual may have been missed using the conventional serum B12 assay. These data demonstrate that there is no problem with falsely negative uMMA and there is no study to date reporting falsely negative uMMA.


The Mayo Clinic Proceedings spotlighted the uMMA test as preferred because of convenience and sensitivity.41

In recent comparative studies, the uMMA test was found more sensitive than the serum B12 assay5 or the SMMA test.20

A study found that patients with neurologic disturbances excreted larger amounts of uMMA than those without neurologic disorders42 and recommend the uMMA assay use to attenuate an important cause of permanent neurologic disability.43

The uMMA test reflects tissue/cellular vitamin B12 deficiency and is the leading candidate as the "gold standard" assay for identifying tissue B12 deficiency.19,21

For test kit requests or more information
E-Mail NCL
Call toll free at 1-800-397-7408

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