Metformin Users Beware! Your Vitamin B12 might be in danger. Learn more about the B.ovatus vitamin B12 heist and what it means for your health.
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The Vitamin B12 heist !
Metformin Users Beware! Your Vitamin B12 might be in danger. Learn more about the B.ovatus vitamin B12 heist and what it means for your health.
There are many medications used to manage type 2 diabetes……….
Each with their pros and cons.
Metformin is an oldie, but a goodie.
Metformin made its debut on the global stage in 1957 when it was introduced in France. Since then, it has journeyed across borders, finding its place on the prestigious WHO essential drug list. With decades of real-world experience, a lot is known about it, a lot, not everything.
Unfortunately exactly how it works is still a somewhat contentious issue, but we’re getting there. Click here to learn more about the latest thinking on how metformin works.
Metformin precipitates vitamin B12 shortages
One thing that is known about metformin, is anyone taking metformin for an extended period of time is vulnerable to a vitamin B12 deficiency.
Regrettably this phenomenon is not always confronted, and it needs to be.
Vitamin B12 shortages are not guaranteed
It doesn’t happen to everyone. Stats suggests it impacts around a third of patients who take it and the longer you take it, the higher the risk. Of course, why it happens also isn’t known.
There are a few theories……..
A team of Chinese researchers decided it was time to get to the bottom of this.
Metformin’s playground
Knowing that metformin does it’s magic mainly in the gut, and since a lot of the action with vitamin B12 happens there too, the team reasoned this was where their investigations should begin.
Vitamin B12 is something gut bacteria need.
A couple of them know how to make it : most beg, borrow or steal it from their neighbours. Yes, there are criminal elements EVERYWHERE, including your gut. Our team had a hunch “someone” was stealing it. And metformin was unwittingly aiding and abetting the thief, so they set about looking for the thief.
Pinpointing the crime
They assessed the vitamin B12 status of “newly” diagnosed type 2 diabetics who had been treated exclusively with metformin, for a period between 12-24 weeks and grouped them into
- Vitamin B12 deficient < 200 pg/ml
- Vitamin B12 sufficient > 200 pg/ml
Next they collected poop samples and human fecal genomic DNA was extracted and sequenced, to take a look at who was who in the zoo.
And there were differences………
When they crunched the numbers Bacteroides ovatus stood out as a potential trouble maker.
Stacked bar plots showing the average percent relative abundances at the genus level for deficiency and non-deficiency groups, respectively. The most abundant taxa are shown as differently colored bars, with lower abundance taxa grouped as a gray bar. © Manyun Chen et al, 2023
Previous research has shown that the Bacteroides clan of bacteria can produce specialized proteins that can get the vitamin B12 off intrinsic factor (this is the carrier our body uses to move vitamin B12 around).
So the team set about exploring how Bacteroides ovatus behaved when it was exposed to increasing concentration of metformin.
In the dish
Bacteroides ovatus LOVED it. Growth rates spiked as reflected by the increase in optical density.
Growth curve B. ovatus with metformin at different concentrations, © Manyun Chen et al, 2023
This growth spike was not seen in other gut residents, the E.coli clan were oblivious to metformin’s presence. Oblivious, there was no impact on growth rate, positive or negative, even at the highest concentrations of metformin tested.
The vitamin B12 connection
The team wondered if the boost in growth might be connected to “the missing” vitamin B12. They knew B.ovatus couldn’t MAKE vitamin B12. So they took a look inside B.ovatus, following it’s exposure to different doses of metformin, to see what happened to the bacteria’s vitamin B status.
Vitamin B12 concentrations inside B. ovatus with metformin at different concentrations. © Manyun Chen et al, 2023
And in a lab dish at least, metformin helps B.ovatus squirrel away vitamin B12.
Genetic studies showed metformin increased the expression of the BtuG protein on the surface of the bacteria, that tugged vitamin B12 in.
The next questions was did this also happen in “the body” ?
Solving the crime
To test this out, they deliberately “infected” colonized young mice with B.ovatus. The helping hand ensured increased levels in both the small intestine and colon of these mice. Suitably primed…… the team proceeded to expose the mice to “normal” doses of metformin for 4 weeks. At the end of this time period, vitamin B12 status was assessed.
Metformin transformed B.ovatus into a vitamin B12 cliptomaniac.
The concentrations of plasma vitamin B12 in mice colonized with B.ovatus and treated with metformin. © Manyun Chen et al, 2023
The effect was only seen when both B.ovatus and metformin were present.
Vitamin B12 a vulnerable nutrient
B.ovatus is not the only potential drain on vitamin B12 supplies. There is a long list of other things that can put supplies at risk.
- Lack of adequate dietary supplies is frequently a problem because vitamin B12 is only available in animal based protein. It’s a nutrient vegans and vegetarians need to pay particular attention to.
- Decreased gastric acid production. This is often a drug induced problem, drugs that are problematic include proton pump inhibitors.
- Bacterial overgrowth in the small intestine (SIBO)
- Inflammation in the gut i.e. gastritis. Chronic alcohol use often precipitates shortages.
- Intrinsic factor deficiency. This can be genetic or acquired (auto-immune condition).
All can compromise vitamin B12 availability.
The problem with metformin
This study showed the shortages of vitamin B12 commonly encountered in patients taking metformin are not due to metformin directly, but happen because metformin unwittingly ends up aiding and abetting a common gut resident. Eish !
This situation needs to be ACTIVELY managed.
Not enough vitamin B12 for trillions
First prize would be to exterminate B.ovatus with an appropriate course of antibiotics. It would work like a charm, but in the long run, the antibiotic treatment would l create TOO MUCH collateral damage.
So this is not an option.
But not doing anything can put you in line for a lot of problems down the line, especially NERVE problems.
Your nerves take the hit.
As a diabetic you’re already at a high risk of suffering from peripheral neuropathy. Stats suggest 20-80 % of type 2 diabetics suffer from diabetic neuropathy and it happens even when glycemic control is good. I suspect B.ovatus is a contributing factor to his high statistic.
Protect yourself
If you’re taking metformin, to manage your diabetes, your vitamin B12 status should be routinely tested.
And steps should be taken to ensure levels are adequate.
This research hints that simply “eating” more or taking an oral supplement might not be enough to counter the impact of the vitaminB12 bandit, metformin is inadvertently aiding and abetting.
NOTE : Vitamin B12 injections bypass the gut (and B.ovatus with it’s clilptomanica tendencies) ensuring the vitamin B12 that you take, actually ends up in your system.
Vitamin B12 Deficiency: Recognition and Management. Am Fam Physician. 2017;96(6):384-389. Robert C. Langan and Andrew J Goodbred.
Further reading
Nervous breakdowns in diabetics start with dispirited blood vessels
Nerve restoration is a three step process, beginning with building blood vessels to bring in the supplies. Nervous breakdowns in diabetics start with dispirited blood vessels
To stick nerves back together use a tube of omega-3 glue
If your peripheral nerves need a little help reconnecting due to an injury or due to a neuropathy, then stick them back together with a little omega-3 glue
Don’t let your gut bacteria eat you out of house and home
When a gut bacteria can’t find something fibrous to chew, it will just eat something else. Good for the bacteria, but potentially dangerous for you !