Metformin and B12 deficiency

cstehansen

This is from the New England Journal of Medicine:

Several studies have linked metformin to development of vitamin B12 deficiency (NEJM JW Gen Med Jul 1 2010 and BMJ 2010; 340:c2181). Now, researchers provide additional data on this potential complication.

In the randomized Diabetes Prevention Program, 3200 adults at high risk for diabetes received metformin, placebo, or intensive lifestyle modification for 3 years (NEJM JW Gen Med Mar 15 2002 and N Engl J Med 2002; 346:393). After the trial was completed in 2002, participants were invited to a follow-up study in which the metformin group was offered open-label metformin. Among 1700 participants with 5-year follow-up, prevalence of vitamin B12 deficiency (≤203 pg/mL) at year 5 was significantly higher in the metformin group than in the placebo group (4% vs. 2%); at a higher cutoff of 298 pg/mL, prevalences were 19% and 9%, respectively. Although differences between groups diminished after 13 years, years of metformin exposure still correlated with development of B12 deficiency at year 13. Patients with metformin-related low B12 levels had elevated homocysteine levels (an expected finding in B12-deficient patients).

@RalfLott

Not sure if you can get to this online without a subscription or not, but here is the link:

http://www.jwatch.org/na41093/2016/04/21/another-look-metformin-and-vitamin-b12-deficiency

KnitOrMiss

So, I'm not going to try to read the whole link, but does that imply that since my B12 level was at 365 pg/ml less than 5 months after starting generic metformin back in 2014 that I was already deficient before starting it, for it to be that low? I have one spot of nerve damage that surfaced, which was actually what triggered me getting that test, that has not healed despite improving my levels. Lately it has begun to intermittently flare these days. I started Glucophage back in January. In October, my levels were down to 690 from 835.

Since I have the nerve issues, I'd been wary of increasing my B12 again... But I'm thinking the nerve issues were related to something or some combination of things that were in that thyroid "formula" I started taking... I'm thinking about bumping the B12 back up every other day or 3-4 times a week...

What are your theories on supplementation, @cstehansen

nvmomketo

For me that would be a win. My B12 is always well above normal. My kids and mom too so I'm thinking it is a genetic thing.

RalfLott

My B12 was at the upper end of the normal range, after months of taking 2000g of metformin + sublingual B12 daily....

cstehansen

KnitOrMiss wrote: »

So, I'm not going to try to read the whole link, but does that imply that since my B12 level was at 365 pg/ml less than 5 months after starting generic metformin back in 2014 that I was already deficient before starting it, for it to be that low? I have one spot of nerve damage that surfaced, which was actually what triggered me getting that test, that has not healed despite improving my levels. Lately it has begun to intermittently flare these days. I started Glucophage back in January. In October, my levels were down to 690 from 835.

Since I have the nerve issues, I'd been wary of increasing my B12 again... But I'm thinking the nerve issues were related to something or some combination of things that were in that thyroid "formula" I started taking... I'm thinking about bumping the B12 back up every other day or 3-4 times a week...

What are your theories on supplementation, @cstehansen

Your numbers seem to be well above the minimum in the article, so I wouldn't worry about it.

I know there are many in this group taking metformin, and I am a firm believer in more knowledge is good, so I thought I should post this.

We also have lots of people here who supplement and pay more attention to diet in general, so this may not be as applicable as it is to the general public. It is like those studies that show eating red meat causes cancer compared to those who are vegetarian. Never mind the fact the meat eaters in the studies also drank more alcohol, smoked more cigarettes, ate less real veggies, ate more processed carbs...... They compare people who are eating vegetarian because they are concerned for their health with people who eat meat (and everything else) just because it is in front of them.

KnitOrMiss

I can tell you that my research show that under 500 is nerve damage range. As low as I was at 365, that's still within the "acceptable range" but it was in permanent nerve damage territory, hence my falling numbers concerned me...

I really need to get enough brain fuel together to read this article and be able to absorb it...

bametels

@cstehansen Thanks for sharing. My mother has had T2D for over 20 years and takes Metformin along with another non-insulin diabetes med (the name is escaping me right now). A few years ago, she was having increasing problems, especially with walking and balance. Eventually, they found she had a very serious B-12 deficiency. Fortunately, monthly B-12 shots have significantly improved the problem. Now, reading this, I'm wondering if Metformin is the cause.

KnitOrMiss

Antacids can interfere, as can hormone therapy (BCP or HRT), and that list has about 15 items on it. Metformin is one of the worst, but it also can compound the risk with other factors. @bametels

bametels

KnitOrMiss wrote: »

Antacids can interfere, as can hormone therapy (BCP or HRT), and that list has about 15 items on it. Metformin is one of the worst, but it also can compound the risk with other factors. @bametels

Thanks for sharing this information, @KnitOrMiss. My mom does not use either hormone therapy or antacids, so we can rule these out as the cause.

KnitOrMiss

bametels wrote: »

KnitOrMiss wrote: »

Antacids can interfere, as can hormone therapy (BCP or HRT), and that list has about 15 items on it. Metformin is one of the worst, but it also can compound the risk with other factors. @bametels

Thanks for sharing this information, @KnitOrMiss. My mom does not use either hormone therapy or antacids, so we can rule these out as the cause.

@bametels - Looks like others are (had to refresh my memory) antibiotics, NSAIDS, anything with potassium in it, anti-convulsants, alcohol, cholesterol meds (Questran and Colestid), folic acid, neomycin, PPI's, HIV meds, chemo meds, gout meds, histamine blockers, etc.

Those are the highlights I found.

poli22

It is my understanding from my Dr. that vit B12 is destroyed in the gut when one is taking metformin, therefore one needs to take the sublingual kind or shots. That may be one of the reasons that your B12 levels are low.

KnitOrMiss

I read that it had something to do with calcium, and while I didn't find the initial resource I saw, this was what I found just now:

"Metformin contributes to serum B12 deficiency by preventing its transfer into the blood through a calcium dependent membrane, leading to decreased absorption. In addition, in order for B12 o be absorbed into the bloodstream it needs an acid environment in the stomach. Age and intake of acid reducing medications, such as anti-acids or proton pump inhibitors increase the likelihood that older adults may suffer from a B12 deficiency as can certain gastrointestinal disorder such as atrophic gastritis and Crohns disease or surgical reduction of the stomach."

http://blog.joslin.org/2014/06/should-you-take-b12-supplements-if-you-take-metformin/

Seems it affects 30+% of Met users.

EDITED TO ADD ADDITIONAL RESOURCE:

"The mechanism of vitamin B12 deficiency with metformin is undoubtedly due to malabsorption of vitamin B12 at its absorption site in the terminal ileum. Initially, it was believed that metformin caused proliferation of bacteria in the small bowel either due to an effect on intestinal motility or an increased intestinal glucose level.[8] However, the current and more likely explanation for metformin-induced vitamin B12 malabsorption and deficiency is that metformin has an effect on calcium-dependent membrane action in the terminal ileum.[9] Absorption of the vitamin B12-intrinsic factor complex is calcium dependent and metformin interferes with this absorption. In support of this hypothesis is evidence that dietary calcium supplementation reverses metformin-induced vitamin B12 malabsorption.[10]"

http://www.medscape.com/viewarticle/719043_3

bametels

KnitOrMiss wrote: »

@bametels - Looks like others are (had to refresh my memory) antibiotics, NSAIDS, anything with potassium in it, anti-convulsants, alcohol, cholesterol meds (Questran and Colestid), folic acid, neomycin, PPI's, HIV meds, chemo meds, gout meds, histamine blockers, etc.

Those are the highlights I found.

Thanks for this additional info. She does take cholesterol and gout medication and has done so for many year. and Because of recurring urinary tract infections, she has had a lot of antibiotics in recent years. Like many seniors, she is on so many meds and unfortunately, it is hard to get her to question her doctors. I'm sure that the combination of meds she takes is responsible for some of the increasing medical issues she is having.

KnitOrMiss

@bametels The scariest thing is that nerve damage from B12 deficiency is usually permanent, whereas the more progressive things can be reversed, and most of us don't notice the nerve things until it's too late. Tests like D3 and B12 should be on the standard CMP, IMO.

sarahtrust

KnitOrMiss wrote: »

So, I'm not going to try to read the whole link, but does that imply that since my B12 level was at 365 pg/ml less than 5 months after starting generic metformin back in 2014 that I was already deficient before starting it, for it to be that low? I have one spot of nerve damage that surfaced, which was actually what triggered me getting that test, that has not healed despite improving my levels. Lately it has begun to intermittently flare these days. I started Glucophage back in January. In October, my levels were down to 690 from 835.

Since I have the nerve issues, I'd been wary of increasing my B12 again... But I'm thinking the nerve issues were related to something or some combination of things that were in that thyroid "formula" I started taking... I'm thinking about bumping the B12 back up every other day or 3-4 times a week...

What are your theories on supplementation, @cstehansen

what are "nerve issues " andhow were they treated?
I have been on metformin for years, then diagnosed anaemia and severe B12 deficeincy , metformin discontinued and had a year of B12 injections , no effects on BG from reduced metformin

sarahkatzenelson452

What are the drawbacks to supplementing b12 sublingual even if your levels are within the accepted norms? Excess b12 leaves the body via the kidneys, I dont think it is poisonous.