What 25 Years of Metformin Did to One Retiree's B12
She took it every morning with breakfast, exactly as prescribed. Her blood sugar behaved. Her checkups were fine. And the whole time, something else was quietly running low.
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If you have taken metformin, a daily heartburn pill, a statin, or a water pill for more than a few years, and you feel more tired, more crampy, or less steady than your "normal" lab results say you should, read Margaret's story before your next refill.
Margaret's Story
"I did everything right."
Margaret is 71. She taught third grade in Ohio for thirty-one years.
In 1999, her doctor started her on metformin. She never missed a morning.
Blood sugar: controlled. Doctor: pleased.
If you had asked her, she would have told you she was one of the responsible ones. Because she was.
Somewhere around year fifteen, the tiredness changed. Not dramatic, just heavier.
The afternoon nap stopped being optional. She started hunting for words she had known her whole life.
Her calves began waking her at 2 a.m., seized up like a fist.
She did what responsible people do: she brought it up at her annual physical.
The labs came back the way they always did. Normal. "It's probably just age," she was told.
She was 66. She believed it. What else would she believe?
Then her practice hired a new nurse practitioner who did something no one had done in twenty-five years of checkups.
She looked at how long Margaret had been on metformin, and she added one test that had never been on the panel.
Vitamin B12.
Low. Not borderline. Low.
After a quarter century of the medication doing exactly what it was supposed to do, it had also been doing something else the whole time.
Making it harder for her body to absorb one of the vitamins her energy and her nerves run on.
Margaret gets B12 injections now, every month. Here is the part she says still bothers her, and the reason this page exists:
"I'm not angry at the metformin. It did its job. I just wish someone had told me it had a cost. I would have paid it back the whole time."
She is not rare. She is the statistic.
What the research says happened to Margaret, and to 1 in 5 people like her
This is not a story the internet made up. It is one of the best documented effects in diabetes care.
It is simply documented in places patients never look.
Share of patients with low or borderline-low B12, Diabetes Prevention Program Outcomes Study[1]
- The same researchers found that each additional year of metformin use raised the odds of B12 deficiency by 13%.[1]
- A separate study published in JAMA found that people who used acid-suppressing heartburn medications for two or more years had a 65% higher likelihood of B12 deficiency.[2]
- The American Diabetes Association's own Standards of Care recommend periodic B12 testing for people on long-term metformin, especially anyone with anemia or nerve symptoms.[3] Ask yourself: has anyone ever ordered one for you?
It Is Not Just Metformin.
The second side effect: the kind that never makes the pharmacy printout.
Every prescription comes stapled to a printout of side effects.
The rashes, the upsets, the “call your doctor if.” Margaret read hers. You have probably read yours.
But there is a second kind of side effect that almost never makes the printout.
Over years, some of the most commonly prescribed medications in America quietly use up, block, or flush out specific nutrients.
The very ones that keep your energy steady, your muscles calm at night, and your feet sure underneath you.
The Cleveland Clinic states it as plainly as a major medical institution can.
On its clinical page about age-related muscle loss, it reports that studies show long-term use of proton pump inhibitors, the daily heartburn pills like omeprazole, can lead to malabsorption of vitamin B12 and magnesium, and that this can lead to muscle weakness, poor balance, and falls.[4]
Cleveland Clinic, Sarcopenia (Age-Related Muscle Loss)Read that chain again, because it connects three things most people have never connected.
A heartburn pill, two missing nutrients, and the steadiness of your own two feet.
Four of the most researched examples. See if your cabinet is on this list:
Statins.
They work by blocking a pathway in the liver, and that same pathway is the one your body uses to make coenzyme Q10, a compound your muscles use for energy. A meta-analysis of randomized trials published in the Journal of the American Heart Association examined CoQ10 supplementation specifically for statin-associated muscle symptoms.[7] It is no accident that so many statin users talk about their legs.
Water pills (diuretics).
They do their job by flushing fluid, and minerals such as magnesium and potassium leave in the same water. The NIH lists diuretic use among the recognized causes of magnesium depletion.[8] Ask anyone who started one and met the 2 a.m. calf cramp the same week.
And here is the backdrop that makes the drain matter more after 60.
48% of Americans already consume less magnesium than their body's estimated requirement, before any medication enters the picture, and older adults are among the highest-risk groups.[8]
B12 tells the same story. Up to 43% of community-dwelling older adults show low or marginal B12 status depending on the measure used, in part because the stomach produces less acid with age, and stomach acid is what frees B12 from food in the first place.[6]
The drain is slow. Years slow. That is exactly why nobody connects it. The fatigue arrives a decade after the prescription, and by then it just looks like age.
Why Your Doctor Never Mentioned It
It is not what you think.
Here is what this page is NOT going to tell you: that doctors are hiding something, or that your medication is the enemy.
Both are false. Margaret's metformin very likely protected her from far worse. Yours is doing its job too.
Your doctor has eleven minutes and three bigger things to cover.
Your pharmacist fills the prescription accurately and moves to the next one.
The guidelines that recommend monitoring, like the ADA's B12 recommendation[3], sit in documents written for clinicians, with no one assigned to act on them.
The Cleveland Clinic's warning about heartburn pills[4] sits on a page about muscle loss that most heartburn patients will never have a reason to visit.
It is not a conspiracy. It is a gap in the job descriptions.
Which means the person who has to mind the drain is the person holding the pill organizer.
Which of these is in your cabinet?
If even one has been there for two years or more, the next section is about you.
What the Drain Feels Like
From the inside.
No two people feel it identically, and every one of these has other possible causes. That is precisely how it hides.
But when several of them cluster together in someone who has been on these medications for years, the pattern has an explanation:
The Put-Back Philosophy
You do not fix a drain by pulling the plug on your medication. You fix it by putting back what goes missing.
This page is about the years before that point: supporting your levels while your medications keep doing their necessary work.
And here is why the bottle you may have already tried probably did not do it:
In other words: if you tried supplements before and felt nothing, there is a decent chance you were right.
Nothing was happening. The form was wrong. That is not a reason to give up on the idea. It is the reason the idea never got a fair test.
Introducing The Medicine Cabinet Refill
Steady in 90 nights. Two formulas, four capsules, one job: put back what your prescriptions use up.
That is the entire protocol. It fits the two moments you already own: breakfast, and lights-out. No new pills at lunch, nothing to remember at odd hours. And this matters: most people notice the nights change first, often within the first week. That is the magnesium. The morning half works quieter and slower, and we will show you exactly what to expect and when.
LongevityRx built the Refill for exactly the people on this page. MitoMultiply is methylated, pre-activated B vitamins built for how absorption works after 60, two capsules with breakfast. Mag18 is peptide-bound magnesium for the muscles that have been waking you at 2 a.m., two capsules before bed. Most people notice the nights change first, often within the first week.
Your order includes $212 in practical tools, free:
Your Order Includes:
BONUS First Three Chapters of Heal Your Cells, by Dr. Will Cole & Dr. Josh Axe
Everything That Comes With It
Because starting is the hard part.
Why I Wrote Heal Your Cells
Everything on this page comes down to one idea: some of the most common long-term prescriptions quietly draw down specific nutrients, and almost nobody ever tells you which ones or what to put back. That gap is exactly why my co-author Dr. Josh Axe and I wrote an entire book about it. Heal Your Cells goes past any single medication to the bigger question underneath, why cellular aging is starting earlier for so many people, and what an actual plan to reverse it looks like. For a limited time, I'm sending you the first three chapters free, ahead of the book's official release.
-
01
Reset Your Cellular Age
Josh opens with his own health crisis, a scare serious enough that a doctor told him he might never walk normally again, and the recovery that followed. It's the case study behind the book's core claim: the body is built to regenerate, and most of what we call "aging" is a slower, everyday version of the same repair process, the same repair process this page is really about.
-
02
Why Our Cells Are Sicker Than Ever
The chapter that explains why the pattern on this page, medications quietly drawing down nutrients, is starting to show up earlier and more often, and why a standard checkup rarely catches it until it's already progressed.
-
03
Chemical Chaos at the Cellular Level
My own chapter, on the everyday exposures most people never think to account for, prescriptions included, and what they're quietly doing at the cellular level.
The 90-Night Guarantee
One phone call to a real person, or a reply to any email we have sent you. Refund on your card within 5 business days. We will ask one question, “what didn't move?”, because it makes us better. Answering it is optional.
Margaret's story has a good ending. A sharp-eyed nurse practitioner, one overdue test, a fixable problem found. But the ending should not have taken twenty-five years, and it should not depend on luck.
The research in this article is not hidden. It is published by the American Diabetes Association, the Cleveland Clinic, JAMA, and the NIH. It simply lives in places patients never look. Now you have looked.
If you take any of the four medications on this page, you do not need to wait for your version of that lucky appointment. Check your cabinet. Score yourself tonight. Put back what the last decade quietly used up, and let your own 90-night scorecard tell you whether it mattered.
Your medications are doing their job. This is the part that was always yours.
About the Author
Dr. Will Cole, MD
Functional Medicine Practitioner
Dr. Will Cole is a leading functional medicine practitioner who works to find the root cause of fatigue, inflammation, and hormone imbalance. After reviewing thousands of genetic profiles in his clinic, he formulated MitoMultiply for Longevity Rx to give the body the methylated nutrients it can actually use.
Frequently Asked Questions
Why isn't B12 checked at a normal physical?+
The standard panel is built to catch disease markers your doctor is watching for at night, like your A1c, blood pressure, and kidney function. B12 is not part of that default panel. The American Diabetes Association's own Standards of Care say measurement should be considered for people on long-term metformin, but "considered" is easy to lose inside an eleven-minute visit unless someone asks for it directly.[1]
How common is B12 deficiency in people on metformin?+
In the Diabetes Prevention Program Outcomes Study, 19.1% of long-term metformin users had low or borderline-low B12 at five years, compared with 9.5% on placebo. By year thirteen, it was 20.3%, roughly one in five. Each additional year of use raised the odds of deficiency by 13%.[2]
What does low B12 actually feel like?+
It tends to show up slowly, which is part of the problem. Tiredness that gets filed under age. Tingling feet that get filed under diabetes. Foggy thinking that gets filed under getting older. These symptoms look exactly like what people already expect to feel in their 60s and 70s, which is why a test matters more than a guess.
Should I stop taking metformin?+
No. Metformin has decades of evidence behind it and has helped protect many people from the consequences of uncontrolled blood sugar. Nothing here suggests stopping or changing it. The point of this page is the nutrient it can quietly use up over time, not the medication's value. Never stop or change a prescription medication without consulting your healthcare provider.
What should I actually say to my doctor?+
Something as direct as: "I've been on metformin for years. Could we check my B12?" This is already inside the ADA's own published Standards of Care, so it is not an unusual request. Bringing a printed summary with citations can help keep the conversation short and specific.
Why does the form of B12 matter?+
Most drugstore B12 is cyanocobalamin, a form your body has to convert before it can use it, and that conversion slows with age. Methylated B12 arrives already in the active form, which is why it's used instead of cyanocobalamin in formulations built for this stage of life.[3]
What if my B12 test comes back normal?+
That's a genuinely good outcome, and the honest majority result: about four out of five long-term metformin users are not in the low range. A normal result means one less thing to wonder about. The point of testing is finding out which group you're in rather than guessing.
The Medicine Cabinet Refill
Steady in 90 nights. Two formulas, four capsules, one job: put back what your prescriptions use up.
That is the entire protocol. It fits the two moments you already own: breakfast, and lights-out. No new pills at lunch, nothing to remember at odd hours. And this matters: most people notice the nights change first, often within the first week. That is the magnesium. The morning half works quieter and slower, and we will show you exactly what to expect and when.
LongevityRx built the Refill for exactly the people on this page. MitoMultiply is methylated, pre-activated B vitamins built for how absorption works after 60, two capsules with breakfast. Mag18 is peptide-bound magnesium for the muscles that have been waking you at 2 a.m., two capsules before bed. Most people notice the nights change first, often within the first week.
Your order includes $212 in practical tools, free:
Your Order Includes:
References
[1] Aroda VR, Edelstein SL, Goldberg RB, et al. Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2016;101(4):1754-1761.
[2] Lam JR, Schneider JL, Zhao W, Corley DA. Proton Pump Inhibitor and Histamine 2 Receptor Antagonist Use and Vitamin B12 Deficiency. JAMA. 2013;310(22):2435-2442.
[3] American Diabetes Association. Standards of Care in Diabetes. Section 9, Pharmacologic Approaches to Glycemic Treatment (metformin and vitamin B12 monitoring).
[4] Cleveland Clinic. Sarcopenia (Age-Related Muscle Loss). my.clevelandclinic.org/health/diseases/23167-sarcopenia.
[5] Xiong G, et al. Association between proton pump inhibitor use and muscle mass: a US population-based study. Aging Clin Exp Res. 2026;38(1):66.
[6] National Institutes of Health, Office of Dietary Supplements. Vitamin B12 Fact Sheet for Health Professionals. ods.od.nih.gov.
[7] Qu H, Guo M, Chai H, et al. Effects of Coenzyme Q10 on Statin-Induced Myopathy: An Updated Meta-Analysis of Randomized Controlled Trials. J Am Heart Assoc. 2018;7(19):e009835.
[8] National Institutes of Health, Office of Dietary Supplements. Magnesium Fact Sheet for Health Professionals. ods.od.nih.gov.
[9] Mishra S, Stierman B, Gahche JJ, Potischman N. Dietary Supplement Use Among Adults: United States, 2017-2018. NCHS Data Brief No. 399.
These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. Consult your healthcare provider before beginning any supplement, especially if you take prescription medications.