Supplements
Vitamin B12: Who Is Actually Low, and the Metformin Angle
The shot does almost nothing if your levels are fine. Here is who actually runs low, why long term metformin is on that list, and what to ask for when the first test comes back normal.
Walk into a med spa and there is a good chance someone will offer you a B12 shot for energy. It is one of the easiest sells in wellness. You are tired, the shot is quick, and the vitamin sounds harmless.
Here is the part that rarely comes up at the counter. B12 does a great deal for people who are actually low, and close to nothing for people who are not. So the useful question is not whether B12 helps with energy. It is whether you are one of the people running low, and there is a fairly short, well studied list of who that tends to be.
Who is actually at risk
Routine B12 screening is not recommended for average risk adults. It is recommended when you have a reason. A clinical review of recognition and management lists the situations worth testing: taking metformin for more than four months, taking a proton pump inhibitor or an H2 blocker for more than twelve months, following a vegan or strict vegetarian diet, being older than 75, having had gastric or small intestine surgery, and having inflammatory bowel disease (Langan, 2017).
Look at that list again. Several of those describe a lot of women, and one of them describes a medication that is handed out constantly.
The metformin angle
Metformin is the most prescribed drug for type 2 diabetes. It is also prescribed widely for prediabetes and for PCOS. And it lowers B12.
A randomized placebo controlled trial followed 390 adults with type 2 diabetes for 4.3 years. Compared with placebo, metformin lowered B12 concentrations by about 19 percent. By the end of the study, the absolute risk of B12 deficiency was 7.2 percentage points higher in the metformin group, which works out to roughly one extra case of deficiency for every 14 people treated over that period (de Jager, 2010).
A longer look came from the Diabetes Prevention Program Outcomes Study, which tracked people for 13 years. At the 5 year mark, low or borderline low B12 showed up in 19.1 percent of the metformin group against 9.5 percent on placebo. Each additional year of metformin use raised the odds of deficiency by about 13 percent. People in the metformin group with low B12 also had more peripheral neuropathy (Aroda, 2016).
That last detail matters more than it sounds. Nerve symptoms from low B12 can look a lot like nerve symptoms from diabetes, so it is easy for the cause to get filed under the wrong heading.
None of this is a reason to stop metformin. It is a very good drug. It is a reason to have your B12 checked if you have been on it for more than a few months, which is exactly what the researchers in both studies recommended.
The acid blocker angle
Your stomach needs acid to pull B12 off the protein in food. Medications that suppress acid interfere with that step.
A review of the evidence concluded that proton pump inhibitors, H2 blockers, and metformin all clearly reduce serum B12 by blocking absorption, each in its own way. What is still unsettled is how often that translates into real, symptomatic deficiency rather than a lower number on a lab report (Miller, 2018).
So the honest version is: if you have been on omeprazole or a similar drug for years, this is worth a conversation and a test, not a panic.
If you eat little or no animal food
B12 is not made by plants. Anyone eating a fully plant based diet without a supplement or fortified foods is running down a stored supply.
A systematic review and meta analysis pulled together 19 studies using the full panel of B12 markers. Vegan adults had significantly lower serum B12 and higher homocysteine than omnivores, a pattern that points to functional deficiency and not just a low reading. The encouraging finding was in the subgroup analysis: vegans who took a B12 supplement had significantly better numbers across every marker (Niklewicz, 2024).
This one is genuinely easy to fix. It just has to be deliberate.
Why the test itself is confusing
Here is the part that frustrates people who have already been tested and told they are fine.
Serum B12 is a blunt instrument. In an analysis of 9,645 US adults, elevated methylmalonic acid, which is a marker of B12 not doing its job inside cells, showed up in 13.5 percent of people whose serum B12 sat in the low normal range and in 4.1 percent of people whose serum B12 looked comfortably normal. It also ran the other way, since plenty of people with a low serum B12 had perfectly normal methylmalonic acid (Wolffenbuttel, 2020).
In other words the test misses people, and it also flags people who are fine. That is why the recommendation for anyone in a high risk group with a borderline result is to add methylmalonic acid rather than accept the first number (Langan, 2017). Measuring two or more markers is more accurate than measuring serum B12 alone (Miller, 2018).
Shots versus pills
This is where the med spa pitch runs into the evidence.
A Cochrane review of randomized trials comparing oral B12 with injections found that 1000 micrograms a day by mouth normalized B12 levels about as well as intramuscular shots, at lower cost. The reviewers rated the evidence low quality because the trials were small, so this is a reasonable conclusion rather than a settled one (Wang, 2018).
The clinical guidance lands in the same place. High dose oral B12, around 1 to 2 mg a day, corrects both anemia and neurologic symptoms about as well as injections. Injections work faster, so they make sense for severe deficiency or severe nerve symptoms (Langan, 2017).
Which means the shot is a real treatment for a real deficiency, and mostly an expensive placebo for a tired person whose B12 is normal.
What B12 will not do
It is worth being clear about the limits, because the marketing is not.
B12 supplementation lowers homocysteine, and for a while that looked like it might protect the heart and the brain. It did not pan out. In people with elevated homocysteine and cardiovascular disease, B12 did not reduce heart attacks or strokes, and it did not slow cognitive decline (Langan, 2017).
Correcting a deficiency is worth doing on its own terms. Taking B12 as general insurance against aging is not supported.
The practical version
If you are on metformin, on a long term acid blocker, eating plant based, over 75, or you have had gut surgery, ask for a B12 test and ask for methylmalonic acid too if the first result comes back borderline.
If you are deficient, oral B12 at 1 to 2 mg a day works for most people. Injections are for severe deficiency, severe nerve symptoms, or absorption problems that pills cannot get around.
And if you are tired with a normal B12, the shot is not your answer. That is worth knowing before you pay for a package of them.
When to see a doctor
Numbness or tingling in your hands or feet, unsteadiness on your feet, memory changes, a sore or smooth tongue, or fatigue that does not lift are all worth a real workup rather than a supplement. Nerve damage from long standing B12 deficiency can become permanent, so this is one where waiting has a cost.
References
- de Jager J, et al. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. BMJ. 2010. PMID: 20488910
- Aroda VR, et al. Long-term metformin use and vitamin B12 deficiency in the Diabetes Prevention Program Outcomes Study. The Journal of Clinical Endocrinology and Metabolism. 2016. PMID: 26900641
- Miller JW. Proton pump inhibitors, H2-receptor antagonists, metformin, and vitamin B-12 deficiency: clinical implications. Advances in Nutrition. 2018. PMID: 30032223
- Niklewicz A, et al. A systematic review and meta-analysis of functional vitamin B12 status among adult vegans. Nutrition Bulletin. 2024. PMID: 39373282
- Wolffenbuttel BHR, et al. Association of vitamin B12, methylmalonic acid, and functional parameters. The Netherlands Journal of Medicine. 2020. PMID: 32043474
- Wang H, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database of Systematic Reviews. 2018. PMID: 29543316
- Langan RC, Goodbred AJ. Vitamin B12 deficiency: recognition and management. American Family Physician. 2017. PMID: 28925645
Common questions
Does metformin really cause vitamin B12 deficiency?
Yes, and it has been measured in randomized trials. In a placebo controlled trial of 390 adults with type 2 diabetes followed for 4.3 years, metformin lowered B12 by about 19 percent and raised the absolute risk of deficiency by 7.2 percentage points, which is roughly one extra case for every 14 people treated. In the Diabetes Prevention Program Outcomes Study, each additional year of metformin use raised the odds of deficiency by about 13 percent. This is not a reason to stop metformin, which is a very good drug. It is a reason to get your B12 checked if you have been taking it for more than a few months.
My B12 came back normal but I am exhausted. Could I still be low?
It is possible, though it is not the most likely explanation. Serum B12 is an imperfect test. In an analysis of 9,645 US adults, 13.5 percent of people with a low normal serum B12 had elevated methylmalonic acid, a marker showing B12 is not doing its job inside cells, and so did 4.1 percent of people whose serum B12 looked clearly normal. If you are in a high risk group, such as long term metformin or acid blocker use, ask about adding methylmalonic acid testing. If you are not in a high risk group and your B12 is solidly normal, fatigue usually has another cause worth chasing, such as iron, thyroid, sleep, or blood sugar.
Are B12 shots better than pills?
Not for most people. A Cochrane review of randomized trials found that 1000 micrograms of oral B12 a day normalized levels about as well as intramuscular injections, and cost less, though the reviewers rated that evidence as low quality because the trials were small. Clinical guidance says high dose oral B12 of about 1 to 2 mg a day corrects anemia and neurologic symptoms about as well as shots. Injections work faster, so they are the better choice for severe deficiency or severe nerve symptoms. If your B12 is normal and you are just tired, a shot is unlikely to do anything.
Do I need a B12 supplement if I eat plant based?
Yes. B12 is not made by plants, so a fully plant based diet without fortified foods or a supplement slowly runs down your stores. A meta analysis of 19 studies found vegan adults had lower serum B12 and higher homocysteine than omnivores, a pattern that points to real functional deficiency rather than just a low reading. The good news is that in the same analysis, vegans who supplemented had significantly better numbers on every marker. This is one of the easier nutrition problems to solve, as long as it is deliberate.
Will taking B12 protect my heart or my memory?
No, not if you are not deficient. B12 does lower homocysteine, and for a while that looked promising for heart and brain health. The trials did not support it. In people with elevated homocysteine and cardiovascular disease, B12 did not reduce heart attacks or strokes and did not slow cognitive decline. Fixing an actual deficiency is worth doing for its own reasons, but B12 as general insurance against aging is not backed by the evidence.
