Total B12 Vs Active B12 And Methylmalonic Acid
Several tests can be used to determine if you are vitamin B12-deficient:
- Total vitamin B12
- Methylmalonic acid
Although total vitamin B12 is the most commonly used test, these 2 additional markers may provide important insight into your B12 status in specific cases.
Active vitamin B12 makes up 6 20% of your total blood vitamin B12 levels . It has a short life and drops much faster than total vitamin B12 when your B12 supplies start running low. For this reason, some experts claim that active B12 is an earlier and more sensitive indicator of vitamin B12 deficiency .
However, measuring active vitamin B12 has several limitations. The lower limit is still unclear and this test may not be more accurate than total vitamin B12. In addition, it is rarely used because of its high cost and limited availability .
Vitamin B12 normally breaks down methylmalonic acid , which builds up only when B12 is low. This is why MMA can be used as a functional indicator of vitamin B12 deficiency. But this test is not perfect either since it often gives false-positive results .
Neither active vitamin B12 nor MMA is reliable in people with damaged kidneys .
Vitamin B12 Deficiency: Signs Symptoms Risks
Without a shadow of a doubt, vitamin B12 is an important source of benefits for health and no human body can function optimally and be healthy without an adequate intake. Vitamin B12 deficiency is prevalent among vegans who do not supplement, and even some categories of vegetarians are at risk for vitamin B12 deficiency, namely vegetarians who do not consume most animal products or in amounts too low to meet their dietary requirements . Women of childbearing age, especially women with endometriosis or non-pathological heavy menses also tend to regularly experience a deficiency.
Signs, symptoms and side effects of vitamin B12 deficiency include:
What Are The Benefits Of Vitamin B12
Some of the biggest benefits of vitamin B12 include:
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Ethics And Statement For Study Checklist
This study was approved by the bioethical committee of Angers University Hospital and has been conducted in accordance with the Declaration of Helsinki. Patients gave informed consent. We applied the strengthening the reporting of observational studies in epidemiology statement to observational studies.
Design Study Cohort And Data Sources
We conducted this population-based cohort study using data from medical registries in Northern Denmark over the period from 1998 to 2010. Data were obtained from the Clinical Laboratory Information System Research Database , the Aarhus University Prescription Database , the Danish Cancer Registry , and the Danish National Registry of Patients . The Danish Civil Registration System, established in 1968, assigns a civil registration number to all residents, allowing for unequivocal individual-level data linkage among all Danish registries .
The LABKA database contains all test results from routine tests performed in hospital laboratories in Northern Denmark, which has a total population of 2.2 million inhabitants. Results of more than 1700 different types of analyses are included in the database. For each analysis, the database stores the test result , civil registration number, date, and the international Nomenclature, Properties and Units code. For some analyses, a local analysis code is recorded. We identified all patients in the LABKA database with a plasma Cbl measurement of greater than 200 pmol/L recorded from 1998 through 2009. If a patient had more than one Cbl test result, only the first test was included in our analysis.
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Total Plasma Vitamin B12 Assay
B12 measurement was centralized in the biochemistry laboratory of Angers University Hospital. Plasma vitamin B12 was identified using competitive immunoassays with direct chemiluminescence on the ADVIA Centaur system . The normal reference range was 200999 ng/l and the coefficient of variation was 1.34.1%.
What Abnormal Results Mean
Values of less than 160 pg/mL are a possible sign of a vitamin B12 deficiency. People with this deficiency are likely to have or develop symptoms.
Older adults with a vitamin B12 level less than 100 pg/mL may also have symptoms. Deficiency should be confirmed by checking the level of a substance in the blood called methylmalonic acid. A high level indicates a true B12 deficiency.
Causes of vitamin B12 deficiency include:
- Not enough vitamin B12 in diet
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Vitamin B6 And Plp Levels
Eight studies reported results on vitamin B6 intake , and five studies reported blood PLP levels . The multivariable-adjusted RRs for each study and all studies combined for the highest vs lowest categories of vitamin B6 intake or blood PLP levels are shown in Fig. . Results from studies on vitamin B6 intake in relation to pancreatic cancer risk were inconsistent, with moderate heterogeneity . All studies on the association of blood PLP levels with pancreatic cancer risk showed an inverse association, which was statistically significant in 2 studies . No heterogeneity was detected . The pooled RRs of pancreatic cancer for the highest vs lowest categories of vitamin B6 intake and blood PLP level were 0.63 and 0.65 , respectively. The Eggers or Beggs test showed no evidence of publication bias for vitamin B6 intake.
Fig. 2
A forest plot of the pooled RR for vitamin B6, blood pyridoxal 5-phosphate levels and pancreatic cancer risk
In the subgroup analyses, we pooled the RR by study design , geographical region , and number of included cases . A statistically significant protective effect of vitamin B6 intake on pancreatic cancer was observed in case-control studies , while no such effect in cohort studies . Also, the inverse associations were found in US , Asia and Australia , but not in Europe . When stratifying by number of cases, the RR estimates showed vitamin B6 intake was consistently associated with reduced risk of pancreatic cancer .
Fig. 3
High Levels Of Vitamin B12 May Be Linked To Increased Cancer Risk
Vitamin B12, which is commonly found in a variety of foods, including fish, meat, eggs, and dairy products, is essential for maintaining the health of the body’s nerve and blood cells it also helps make DNA. Now, researchers in Denmark have found that higher than normal levels of this necessary vitamin may indicate a person is at risk of developing certain cancers. Their study appears today in the Journal of the National Cancer Institute.
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Vitamin B12 And Its Health Benefits
Vitamin B12, also known as cobalamin, is a water-soluble vitamin commonly found in fish, animal products like milk, meat and eggs, and in some plants and plant products like fermented soy products and seaweeds. Vitamin B12 helps in keeping the nerve and blood cells healthy and is necessary for making DNA. Deficiency of Vitamin B12 is known to cause anemia, weakness and fatigue and hence we try to include foods containing Vitamin B12 in our daily diet or alternatively use Vitamin B12 supplements. However, there are rising concerns on long term use of high dose Vitamin B12 and its association with the risk of cancer.
Can Vitamin B12 Cause Cancer
In recent years the concern that an excess of vitamin B12 can cause cancer has sparked quite a lot of debate in the medical community, and not just in professional settings. The increase in cancer risks was either attributed to vitamin B12 itself provided as a dietary supplement to those with anemia or other health issues requiring supplementation, or to carcinogenic compounds found in foods naturally high in vitamin B12 such as red meat.
But is it vitamin B12 that really causes cancer, or an increase in the risk of developing certain cancers, or is it other cancer-causing agents found in foods naturally containing vitamin B12 or in vitamin B12 supplements? Is there any research to indicate a correlation between vitamin B12 and an increased risk of cancer? And which cancers? Is vitamin B12 a cancer cure or risk?
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Vitamin B1: Not A Carcinogen
Research does not reveal vitamin B12 as a carcinogen, that is, a cancer-causing agent. If anything, vitamin B12 is an essential dietary nutrient, one without which the human body cannot do. So how is it possible that studies link high levels of circulating vitamin B12 to an increased risk of certain cancers? Is it possible that vitamin B12 is not the reason behind the higher incidence of cancer observed in people with high blood levels of vitamin B12? Possibly.
For one, there is no research to definitively prove that vitamin B12 is a carcinogen. Secondly, studies that have linked high vitamin B12 blood levels to increased risks of certain cancers have only correlated the high vitamin B12 levels and the higher cancer risk based on a pattern of co-occurrence. Vitamin B12 has not been identified as a cause, but rather as a marker that indicates the need to investigate a potential pathology, cancer or another.
Thirdly, high blood levels of vitamin B12 do not occur in otherwise healthy individuals who meet their nutritional requirements from a varied and balanced diet, and maybe only occasionally supplement to account for minor losses due to stress, menses, childbirth, nosebleeds, minor wounds or other causes asking for temporarily increased dietary requirements.
Side Effects And Risks Of A B
You might feel a pricking when your healthcare provider inserts the needle into your arm. But a blood draw is low risk and generally painless. Its also possible to feel a little sore or observe bruising on your arm for a few days after. Alert your healthcare provider if the pain is throbbing or if your arm swells after the test.
Talk to your doctor before the test if you have a bleeding disorder, such as hemophilia, or if youve had problems with blood clotting in the past. Its possible to experience excessive bleeding where the needle punctures your skin.
Its also important to tell your doctor about any medications or over-the-counter drugs youre taking, as certain drugs may interfere with the test results.
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Health Effects Of High Levels
It was long thought that high vitamin B12 levels werent harmful, but a significant number of emerging studies have linked high B12 blood levels and B12 supplementation to higher cancer risk and mortality.
However, much like the studies linking folic acid to cancer, the studies below are not conclusive. Many point only to an association, not causation. More large-scale and well-designed research is needed.
1) Associated with Higher Risk of Cancer
In a study of over 333,000 people without cancer, the risk of cancer increased with higher B12 levels and was highest during the first year of follow-up. The risk was particularly elevated for blood-, smoking-, and alcohol-related cancers .
Similarly, in over 476,000 people without cancer or vitamin B12 prescriptions , high B12 levels were linked to a higher incidence of cancer .
A large-scale study looked at 5,000 lung cancer-control pairs and reviewed genetic data of 29k cancer patients and 56k healthy people. Higher blood vitamin B12 was associated with higher lung cancer risk. In addition, genetic variants linked to higher vitamin B12 levels were also linked with higher overall lung cancer risk .
Two meta-analyses of 6 and 7 studies, respectively, linked higher vitamin B12 levels to a small increase in the risk of prostate cancer .
2) Associated with All-Cause, Heart Disease, and Cancer Mortality
Several studies of hospitalized patients found a link between higher B12 levels and mortality .
Description Of The Population
Between January 2007 and May 2015, 9,198 patients underwent at least 2 measurements of B12 in our center, excluding the intensive care and maternity units. Among these patients, plasma B121000 ng/L at T1 were found in 344 patients without any known elevated-B12-related causes. Among these 344, 144 patients had a B121000 ng/L at T2 and 200 patients had a B12< 1000 ng/L at T2 . The 344 patients in the NN group were randomly selected from the 7,889 patients with plasma B12< 1000 ng/L at T1 and T2. The flowchart is detailed in Fig. .
Figure 1
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Risk For Ttp According To Vitamin B12 Level
Abbreviations: TTP, time to progression HR, hazard ratio CI, confidence interval.
P values by Cox proportional hazard model.
aLiver lesion included hepatocellular carcinoma and liver metastasis.
bAdjusted for age, sex, Eastern Cooperative Oncology Group Performance Status, and concurrent chemotherapy.
Patient And Cancer Subtypes
The standardized incidence ratios for inpatients and outpatients showed similar associations, both overall and by cancer group. The highest risks again were found for smoking- and alcohol-related cancers and for hematological cancers. The estimates were highest for inpatients in all cancer groups, although cancer risk was elevated also for outpatients with high Cbl levels .
When we examined the association between high Cbl levels and specific cancer types within the first year of follow-up , we found associations with gastric , colorectal , liver , pancreatic , lung , renal , urinary bladder , lymphatic leukemia , myeloid malignancies , non-Hodgkin lymphoma , and multiple myeloma . The associations increased with higher Cbl levels and were greatest among patients with the highest Cbl levels . The cancer risk remained elevated after the first year of follow-up for liver, pancreatic, lung cancer, and myeloid malignancies, with highest standardized incidence ratios observed for patients with Cbl levels greater than 800 pmol/L .
Risk of specific cancer types within the first year after plasma cobalamin measurement. The figure shows the 1-year standardized incidence ratios with corresponding 95% confidence intervals disaggregated according to Cbl levels: x: 200 to 600 pmol/L o: 601 to 800 pmol/L and : greater than 800 pmol/L. The vertical gray line indicates standardized incidence ratio of 1. All statistical tests were two-sided.
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Elevated Vitamin B12 Levels And Cancer Risk In Uk Primary Care: A Thin Database Cohort Study
Corresponding Author:
Note: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers & Prevention Online .
Corresponding Author:Cancer Epidemiol Biomarkers Prev
Johan F.H. Arendt, Henrik T. Sørensen, Laura J. Horsfall, Irene Petersen Elevated Vitamin B12 Levels and Cancer Risk in UK Primary Care: A THIN Database Cohort Study. Cancer Epidemiol Biomarkers Prev 1 April 2019 28 : 814821.
Vitamin B12 And Colorectal Cancer Risk
In a clinical trial study, named the B-PROOF trial, done in Netherlands, the researchers assessed the effect of daily supplementation with vitamin B12 and folic acid , for 2 to 3 years, on fracture incidence. Data from this clinical trial was used by researchers to further investigate the impact of long term supplementation of Vitamin B12 on cancer risk. The analysis included data from 2524 participants of the B-PROOF trial and was found that long term folic acid and vitamin-B12 supplementation was associated with a high risk of overall cancer and a significantly higher risk of colorectal cancer. However, the researchers suggest confirming this finding in larger studies, in order to decide whether Vitamin B12 supplementation should be restricted to only those with a known B12 deficiency .
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Plasma Vitamin B12 Assay
The B12 measurements were centralized in the biochemistry laboratory of Angers University Hospital. The tests were carried out on an immunoanalytical system ADVIA Centaur with ADVIA Centaur VB12 reagents.
An elevated B12 level was defined as1000 ng/L,,,,.
In patients with three or more B12 measurements and at least one B121000 ng/L, T1 was selected as the first test with B121000 ng/L. In the absence of B121000 ng/L, T1 was randomly selected between the first and the penultimate B12 measurement. T2 was the test immediately following T1 with at least 1 month between T1 and T2. As the study aimed at comparing persistent and non-persistent elevated B12, patients who had only the last measurement1000 ng/L were excluded.
Vitamin B12 And Lung Cancer Risk
In another international study published recently, the researchers analyzed the results from 20 population based studies and data from 5,183 lung cancer cases and their matched 5,183 controls, to evaluate the impact of high vitamin B12 concentration on cancer risk via direct measurements of circulating vitamin B12 in pre-diagnostic blood samples. Basically, the idea was to check whether high Vitamin B12 status was an indication of increased risk of lung cancer. Based on their analysis, they concluded that higher vitamin B12 concentrations are associated with increased risk of lung cancer and for every doubling levels of Vitamin B12, the risk increased by ~15% .
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