If (like many people today) you’ve been searching for a way to improve energy levels, chances are you’ve come across a vitamin B12 ad in your Google search. B12 (aka cobalamin) is a water-soluble vitamin required for dozens of bodily functions, including red blood cell production, DNA synthesis, cognitive functioning, neuronal health, and, yes, energy production.
B12 is found in animal-based foods such as fish, red meat, eggs, poultry, and dairy products. Although access to B12 is not typically an issue (for omnivores), regular consumption of these foods does not necessarily mean you are B12 sufficient. Other factors can influence B12 digestion and absorption, such as gut conditions, low stomach acidity, and long-term use of popular medications. Therefore, B12 supplementation is a relatively common occurrence, and 24% of men and 29% of women reported using a supplement containing B12 between 2017-2018. That number likely has grown.
If you have read “Should You Take a Supplement?” and have decided B12 is right for you, keep reading. The following paragraphs will help you navigate the overwhelming supplement aisle so you can find a B12 supplement with confidence.
Understanding the Different Forms of B12
Vitamin B12 comes in several forms, yet there are two primarily found in most supplement formulas: methylcobalamin or cyanocobalamin. Methylcobalamin (MeCbl) is a naturally occurring compound found in food sources such as fish, meat, eggs, and milk. Two other natural forms of vitamin B12 are commercially available, although less common, and include adenosylcobalamin (AdCbl) and hydroxycobalamin (OHCbl). All three forms have been shown in clinical studies to improve vitamin B12 status. Another popular form, cyanocobalamin (CNCbl) is a synthetic B12 compound commonly used for food fortification and supplementation due to its chemical stability and low cost.
Regardless of the form taken, all appear to undergo cellular metabolism to be reduced to the core cobalamin molecule and then converted into MeCbl or AdCbl – the two active forms of B12 used by the body. Furthermore, all forms of B12 have been shown to improve vitamin B12 status. However, before you reach for just any formula, there might be some other factors you might want to consider.
First, animal and human studies have found similar absorption rates, yet, lower tissue retention and increased urinary excretion of CNCbl compared to MeCbl, AdCbl, or OHCbl. The studies’ authors concluded that while CNCbl absorption is up to par, it has lower efficiency in cellular uptake and metabolic activation. Of note, these studies were conducted many years ago, and more recent evidence would be ideal in discerning the difference in retention and utilization of CNCbl.
Secondly, scientists have expressed concern about the cyanide group attached to CNCbl. Some fear that the chronic use of CNCbl may lead to the accumulation of cyanide in human tissues. This issue may be of particular concern for smokers, as smokers tend to have an excess of thiocyanate in their blood, which can disturb the metabolism and use of CNCbl. While more research in this area is needed before a definitive conclusion can be made, CNCbl may be an inferior choice for supplementation despite the lower cost.
Understand B12 Supplement Methods
Vitamin B12 found naturally in food is bound to protein and must be freed with the help of enzymes and stomach acidity before the body can use it. Unlike vitamin B12 found in food, supplemental B12 is not bound to proteins. Therefore, B12 bioavailability from nutritional supplements may be more readily available and is not impaired in cases of low stomach acidity.
Vitamin B12 supplements can be purchased over-the-counter in tablet or pill form, as part of a B12 complex or multivitamin, or as a liquid or spray taken sublingually. B12 can also be prescribed by a doctor, if medically necessary, and can come in the form of a nasal spray or shot. For this article, let’s focus on over-the-counter options since a doctor will likely guide your supplementation if a severe deficiency is found and a prescription is necessary.
There seems to be a lot of information suggesting that sublingual is the best delivery method for B12. But that claim does not seem to stand up to scientific evidence. One double-blinded, randomized controlled study set out to evaluate the relative efficacy of sublingual (SL) and oral (PO) vitamin B-complex administration. Patients assigned to the SL group were provided a sublingual vitamin B complex, and a matching orally delivered placebo. Patients in the PO group were given an oral vitamin B complex, and a matching sublingually delivered placebo. After 6-weeks, the researchers detected no statistically significant difference between the two. They concluded there is no difference in efficacy between SL and PO delivery methods.
Another study conducted over eight weeks in subjects with preclinical cobalamin deficiency provided subjects with 500 micrograms of B12 in one of three forms: (i) sublingual; (ii) oral tablet; (iii) oral vitamin B complex, which also included other B vitamins. All treatments effectively corrected cobalamin deficiency, and neither treatment group was significantly different from the other. As of yet, no evidence suggests a difference in efficacy between oral and sublingual forms.
Relying on cobalamin from a multivitamin alone may be a different story. Cobalamin can be degraded or converted to a cobalamin analog in the presence of vitamin C and copper, which are commonly found in multivitamin formulations. So, if a true cobalamin deficiency exists, be weary of relying solely on vitamin B12 found in multivitamin formulations. Taking it alone or as part of a B12 complex will likely be more helpful.
How Much Vitamin B12 Should I Take?
The Dietary Reference Intake (DRI) for vitamin B12 is 2.4 micrograms per day for adults. According to USDA Survey data from 2010, many American adults exceed these recommendations easily through diet alone. Consuming enough B12 from doesn’t seem to be the issue for most (unless a vegan or vegetarian diet is followed). The problems seem to lie in each person’s ability to absorb and utilize B12.
Many scientists argue that the DRI of 2.4 micrograms is not enough for anyone. A group of researchers out of Denmark recommended daily intakes likely vary between 2.4 – 6 micrograms per day based on various individualized factors. A Norwegian study supported these findings concluding that dietary B12 intake between 6 – 10 micrograms per day is more likely to ensure maximal plasma vitamin B12 concentrations.
Another more recent study out of Denmark affirmed this information, concluding that 4 – 7 micrograms of vitamin B12 is associated with adequate B12 status. Although an exact number has yet to be nailed down, it appears that most agree that 2.4 micrograms is simply not enough.
Moreover, sufficient intake of the vitamin does not always ensure optimal cobalamin levels. The best way to determine if you are consuming adequate amounts of vitamin B12 in whole food or supplement form is to regularly test your B12 status.
Measuring Your B12 Status
Serum B12 is the most used screening test for vitamin B12 deficiency, but research suggests it may not be the best indicator. In fact, in clinical practice, normal serum B12 concentrations do not exclude the diagnosis of B12 deficiency. Weird, we know. One study found that measuring serum B12 may only identify true deficiency in 22% of cases.
While there is still debate on this topic, those who use serum B12 tests follow these clinical set points: B12 above 300 pg/mL is normal, B12 levels between 200-300 pg/mL are considered borderline, and B12 levels below 200 pg/mL are considered deficient.
Overall, many in the scientific community have determined that the predictive strength of blood concentrations of cobalamin is insufficient for a diagnosis of deficiency. Don’t panic; there are other methods of measuring B12 status. Some ways gaining popularity include plasma total homocysteine (tHcy), plasma MMA, and urinary MMA (uMMA). Interestingly, when measuring tHcy, MMA, and uMMA, high values (instead of low values) will indicate vitamin B12 deficiency. This is because cobalamin is required for the metabolism of these products. Low cobalamin levels = high amounts of intermediate product buildup.
tHcy has been found to be a sensitive indicator of clinical cobalamin deficiency, often using tHcy of 16 micromol/L, 15 micromol/L, or 12 micromol/L as an upper limit. However, cobalamin deficiency only accounts for a minority of all high tHcy levels. Other common causes include folate deficiency, alcohol abuse, hypothyroidism, or other drugs and diseases. This might make it challenging to tease out the true cause of elevated tHcy levels.
Elevated MMA in plasma or urine indicates vitamin B12 inadequacy and has been found to be a useful and sensitive functional biomarker of vitamin B12 status. uMMA is a less common but possibly a more accurate measure of B12 deficiency.
Studies have found that fasting uMMA concentration corrected for creatinine (to rule out renal dysfunction) is highly, linearly correlated with serum MMA samples and has high sensitivity and specificity for subnormal B12 concentrations. This means that uMMA may help you catch low vitamin B12 levels before clinical deficiency and side effects appear.
Optimal B12 status is indicated when uMMA results are below 2.0 mmol/mol creatinine. Testing uMMA with a simple urine collection after a night’s sleep can be an easy and accurate way to determine B12 status.
Other Things to Consider Before Supplementing with B12
Absorption of cobalamin from supplements will depend on the dose and frequency of intake. In the gut, B12 is actively absorbed through transport proteins. This means that the number of transport proteins available limits the absorption of B12. When those proteins become saturated, no more B12 can be absorbed at that time, even if more B12 is present.
According to one (quite old) study, intestinal absorption is limited to around 1.5 micrograms per meal. However, this is supported by another more recent study that estimated the absorptive capacity of cobalamin as 1.5-2 micrograms per meal. Absorption capacity is thought to recover to baseline levels within 4-6 hours, allowing for efficient absorption of the next dose. Therefore, smaller amounts of B12 taken over the course of the day may help optimize B12 absorption.
It is also important to note that some common medications can interfere with the absorption or metabolism of vitamin B12. Proton pump inhibitors (PPIs) (commonly used by, well, everyone) are a class of drugs that treat gastroesophageal reflux, better known as GERD. PPI medications reduce the secretion of gastric acid in the stomach, which is required to free B12 bound to food to be absorbed. Metformin, another common drug utilized in non-insulin-dependent diabetics, inhibits B12 absorption. If you commonly use either of these medications, be sure to speak to a trusted healthcare provider about your B12 status.
Lastly, choose a supplement from a manufacturer you trust. With very little oversight in the supplement industry, it’s common (over 20% of supplements tested) to come across supplements tainted with unapproved ingredients or labeled inaccurately. An excellent way to quickly identify companies whose labels you can trust is by looking for a Third-Party Testing quality assurance seal. A Third-Party Testing Seal indicates the product was manufactured correctly, contains the ingredients listed on the label, and does not contain harmful levels of contaminants.