Your Questions Answered: Clinical Insight Into Vitamin B12

 

During the Clinical Insight into Vitamin B 12 webinar, presented by Dr. Roman Pawlak, Associate Professor of Nutrition at East Carolina University, there were questions that could not be answered in the time allotted.  Dr. Pawlak has answered those questions here.

Q. Does everyone using metformin become vitamin B12 deficient?

I am unable to predict whether a specific patient develops vitamin B12 deficiency. I can say, however, that both metformin dose and duration of use have been associated with low vitamin B12 status.

Q. Can you explain ferritin again and how iron metabolism is impacted by vitamin B12 deficiency?

Simply, if ferritin levels are not depleted yet Hg is indicative of inadequate iron status, the low Hg may be related to inadequate B12 rather than iron. This is because Hg concentration reflects both iron intake and stores. When ferritin level is normal or high, Hg level should not be low even when intake is inadequate. Thus, low Hg in the presence of normal ferritin may be indicative of an impairment in Hg synthesis related to inadequate B12 rather than subnormal iron status.

Q. What about the anemia of chronic disease? Won’t you see a low hemoglobin and possibly increase ferritin in anemia of chronic disease.

This is a completely different condition. It is related to inflammation and is associated with low Hg and normal or elevated ferritin. In addition, you will also see elevated markers of inflammation.

Q. What causes the variation in vitamin B12 losses?

Nutrient losses depend on a variety of factors. Generally speaking, when the status of a given nutrient in inadequate losses is lower as the kidneys are doing their best to conserve that nutrient. In one of the studies that I included in the presentation, authors reported that “the rate of loss was a fixed percentage of the total body store of vitamin B12, regardless of the store size: the larger the body store, the larger the losses.” Nutrient losses may also be related to kidney function. Nutrient losses also depend on the life stage and are usually lower in adolescents, and pregnant and lactating women.​

Q. I have been vegan for 5 months and my B12 came back at a toxic level 1888 pg/mL, even though I was only taking the recommended amount of B12 supplement MOST days. Why would this be?

I do not know. One possible reason is a discrepancy between the dose of a supplemented stated on the label vs. its actual dose. Cases of vitamin D toxicity have been reported when the actual doses of the supplement were many times higher than what the label stated. Perhaps this may be the case here?

@ this will not fully answer your question but “The IOM did not establish a UL for vitamin B12 because of its low potential for toxicity”  reference: https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/#h8

B12 is generally considered not to be toxic. However, adverse health effects of very high B12 have been reported. They mainly show as dermatological symptoms that include redness and itching of the skin.

Q. So my 1888 B12 level indicates MTHFR defect?

In order to determine whether or not you have the MTHFR gene defect, you need to have the analysis done for that specific defect. Low or high B12 cannot be used in the determination of your MTHFR gene status.

Q. I’ve heard that blood-related consequences of vitamin B12 deficiency (anemia) are reversible but cognitive and neurological changes are not. Is that true?

Hematologic symptoms of B12 deficiency can be very rapidly reverse, while the impact on neurological symptoms depends on a few factors, including the types of symptoms, their severity and the patient him/herself. Symptoms, such as tingling, feeling pins and needles and even restless leg syndrome can be relatively quickly reversed. However, neurological symptoms can include paralysis and walking difficulties (check out my article on my website www.drromanpawlak.com for more symptoms), which would be much harder, and in some cases, impossible to treat. Also, neurological symptoms in infant and children will take months or even years to treat with varies degree of recovery.

Q. When B12 is deficient you will find ferritin to be low, while it will be high in iron deficiency? I just want to make sure I’m understanding that correctly.

Simply, if ferritin levels are not depleted yet Hg is indicative of inadequate iron status, the low Hg may be related to inadequate B12 rather than iron. This is because Hg concentration reflects both iron intake and stores. When ferritin level is normal or high, Hg level should not be low even when intake is inadequate. Thus, low Hg in the presence of normal ferritin may be indicative of an impairment in Hg synthesis related to inadequate B12 rather than subnormal iron status.

Q. Serum B12 <200 but normal homocysteine and normal MMA — is it just the early stages of B12 deficiency?

Both homocysteine (Hcy) and methylmalonic acid (MMA a test may be used to help diagnose an early or mild vitamin B12 deficiency) depend on more factors than just B12, including more nutrients (eg. folate). Regardless of Hcy and MMA status, I am convinced that serum B12 < 200 (regardless whether pmol/L or pg/ml) is inadequate. I cannot say whether it is an early stage or not but I am convinced that it is inadequate.

Q. How easy is it for the consumer to track B12 intake? The yogurt and milk in my fridge don’t list B12 content.

In my opinion, considering that many foods contain B12 and that there is a huge variation in the amount of B12 in these foods and considering that B12 content if further depended on food preparation method (e.g. cooking, heating, etc.), it would be extremely difficult to actually assess intake. Consumers who may be in one of the groups with a high risk of inadequate B12 status should be advised to request a B12 assessment at their annual checkup. The problem with that is, a handful of physicians is able to correctly interpret B12 lab reports.

Q. How much nutritional yeast is recommended?

2-3 Tbsps/day

Q. How effective is a multivitamin (MVI) in treating B12 deficiency?

Any amount of ingested B12 may help in maintaining B12 status. However, cases of B12 deficiency among individuals taking MVI have been published. Thus, I wouldn’t rely on MVI. Periodically assessing B12 status should be a prudent practice to make sure the status is adequate.

Q. Is there a way to know when it is time to go to injectable B12 rather than oral forms?

Both B12 injections and oral supplements have about the same outcomes in terms of B12 treatment and maintenance of B12 status. The difference is the frequency of application. In treatment, injections are usually given daily or every other day for just a few times followed by monthly maintenance therapy, while supplements are given daily long term. Also, injections may be associated with mood swings. People feel better in the few days following the injections and progressively worse in days just prior to the next scheduled injection.

Q. How (what lab testing) is MTHFR (methylenetetrahydrofolate reductase mutationtest may be used to detect two relatively common mutations in the MTHFR gene that are associated with elevated levels of homocysteine in the blood) deficiency diagnosed? When would you suspect it?

One needs to go to a physician and request the test to be performed. Tests are usually done when patients show signs of B12 deficiency and laboratory tests confirm low B12 and elevated homocysteine.

Q. I often see elevated serum B12. Can you address some reasons why elevated serum B12 may occur, and if there could still be underlying deficiency despite elevated serum levels?

Elevated B12 is usually seen in patients with liver disease, including liver cancer. Also, since B12 is water soluble and, in normal conditions, the kidneys should get rid of the “extra” B12, high B12 may reflect kidney insufficiency. High B12 may also be found among patients with leukemia. Patients with unusually high B12 can still be deficient in B12. This is because serum/plasma B12 reflects both B12 found in the haptocorrin and holotranscobalamin. The bulk of B12 in serum is found in the former, which has no physiological function. It is this B12 protein carrier (haptocorrin) that is elevated in the presence of adverse health conditions, which accounts for the high serum B12. Thus, a patient may have high B12, accounted for by high haptocorrin, and be B12 deficient, indicative by low holotranscobalamin status.

Q. Can you repeat how platelet count may be indicative of B12 status?

B12 deficiency results in pancytopenia (abnormally low status of all blood cells). So, low platelet count may reflect inadequate B12 status. By the way, the same may be true of white blood cells as their synthesis is also dependent on B12 status.

Q. Has anyone studied the effect of Statins on muscle degeneration in older adults who are Vita B12 deficient?

I have seen some references to statins and B12 in a few websites but I do not remember seeing a study that showed an association of B12 status with statins.

Q. Can over supplementation also cause elevated b12 serum levels (in excess of 1000) in the absence of cancer or other problems with the liver.

Yes. This is why a supplemental dose should be verified with biochemical evaluation on B12.

Q. What is the recommended dose for EPA/DHA

IOM did not specify a dose. However, studies have shown that when it comes to reducing CVD risk, a dose of between 250 to 500 mg/day is needed. A higher dose does not show any additional protective effect.