New Metformin Warning: Mandatory Supplementation with Vitamin B12
Metformin, one of the most popular medications in the world, has been shown to cause a vitamin B12 deficiency. A vitamin B12 deficiency may be especially high among elderly individuals, persons who take a high dose of metformin and/or with long term treatment. A vitamin B12 deficiency is serious as it can cause permanent damage to the brain and nervous system. Here's what you need to know to avoid a vitamin B12 deficency if you take metformin.
Metformin is a medication that became available in the U.S. in 1995 for the treatment of type 2 diabetes. Metformin is the most widely used medication used to lower insulin levels in those with polycystic ovary syndrome. Other names for metformin include glucophage, glucophage XR, glumetza, and fortamet. Metformin lowers blood glucose levels in three ways:
1. It suppresses the liver's production of glucose.
2. It increases the sensitivity of your liver, muscle, fat, and cells to the insulin your body makes.
3. It decreases the absorption of carbohydrates you consume.
Metformin and B12 Deficiency
Metformin use may affect the absorption of vitamin B12 possibly through alterations in intestinal mobility, increased bacterial overgrowth, or alterations of the vitamin B12-intrinsic factor complex. While studies have shown that metformin lowers stores of vitamin B12 in persons with diabetes, only one study has examined metformin and B12 status among women with PCOS. In 2009, Kaya et al. found that vitamin B12 concentrations were significantly lower in obese PCOS women in comparison with obese control women. Women with PCOS tend to take higher amounts of metformin (average dose is 1,500-2,000 mg daily) than those with diabetes to help manage insulin resistance. Both long-term use and high dosage intake as seen in the PCOS population, are risk factors for vitamin B12 deficiency.
About Vitamin B12
Vitamin B12 is a water-soluble vitamin that is required for proper red blood cell formation, neurological function, and DNA synthesis. There's some evidence that vitamin B12 may help prevent heart disease and possibly even Alzheimer disease. This vitamin is found primarily in animal foods, such as beef, seafood, eggs, and dairy products, which is why some vegans are at risk for a B12 deficiency (click here for food sources of B12). Elderly people are often at risk for deficiency as well, due to problems with absorption from the gastrointestinal tract.
Symptoms of B12 deficiency include certain types of anemia, infertility, neuropathy (nerve damage), chronic fatigue, memory loss, confusion, and even dementia. Pernicious anemia, a severe form of long-term vitamin B12 deficiency is an autoimmune disease that affects the stomach. If pernicious anemia is left untreated, it causes permanent nerve and neurological damage. Symptoms of pernicious anemia are sometimes misdiagnosed as diabetic peripheral neuropathy and include: chronic fatigue, dizziness, loss of appetite, nerve pain, depression, confusion and difficulty concentrating. If you experience any of these symptoms, see your doctor immediately.
What you can do
Individuals who take metformin get B12 levels checked annually. A simple blood test can assess vitamin B12 status. Values below approximately 170-250 pg/mL (120-180 picomol/L) for adults indicate a vitamin B12 deficiency, yet, optimal ranges should be >``450 pg/mL. Elevated serum homocysteine and urinary methylmalonic acid (MMA) levels, the gold standard in assessing B12, also indicate a B12 deficiency.
All individuals age 14 or higher need 2.4 mcg B12 daily. Women who are pregnant or nursing will need slightly more. Mandatory supplementation with B12 has now been proposed for those taking metformin. Taking a daily multivitamin containing 100% of the daily value (DV) for vitamin B12 will do the trick.
Let us know: are your doctors routinely checking your B12 levels? Were you found to have a deficiency?
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I was feeling really run down after started taking Metformin and a Physical Therapist friend of mine said she got B12 shots to give her more energy, so I looked into the B12 deficiency and Metformin. I discovered this correlation when I did my own research back about 12-15 months ago. I shared this connection with my Gyno. She now recommends B12 supplement to all PCOS patients taking Metformin.
Posted by: Dorothy Joseph | April 27, 2011, 11:18 am
Great web site! Thanks for posting this important piece of information about metformin and vitamin B12 deficiency.
It's crucial for diabetics to be aware of the risks so that they can avoid becoming B12 deficient and developing severe nerve damage.
Thanks for allowing my comments.
Posted by: Linda Socher | May 5, 2011, 11:34 pm
This is good information to know. My daughter has been on metformin for PCOS for a couple of years now, and no one has ever mentioned the need to check a B12 level. Lately she feels her hair is falling out excessively/more than normal and that it's noticably thinner. She also takes spironolactone and birth control pills. She recently read that women with PCOS may be more prone to zinc deficiency. Is there any evidence for zinc deficiency with PCOS?
Posted by: Jackie | May 28, 2011, 11:46 am
If the deficiency is the result of changes to intrinsic factor then a multi with B12 in it is unlikely to be helpful. Intrinsic Factor is responsible for the absorption of B12 in the gut, if it's not working you can't absorb B12 from oral doses.
You would need either an injection or the sublingual/chewable version of B12. Also 2.4mcg will be the RDA for B12, enough to prevent outright deficiency symptoms in otherwise healthy people, but probably not enough in these sort of circumstances.
Posted by: Gail | June 1, 2011, 7:31 pm
I have been seeing an FNP for approximately 3-years for PCOS and I am being treated with 1500mg/day of Glucophage. I recognized mental acuity changes, difficulty concentrating,etc. and researched Glucophage and found it impairs B12 absorption so I asked that a B12 level be drawn. I called for my results a week later to find that my level was 285 and on the low end of the reference range of 211-946. The FNP had made a note in my chart that it was "okay to begin supplementation with OTC B12."
Posted by: Adele Downer | December 28, 2011, 10:24 am
I have been doing a bit of research on this as well. There is now a vitamin B12 patch that can be used instead of injections, and there is no need to worry about absorption issues.
Posted by: Renae | March 9, 2012, 12:59 pm
I've been taking metformin for 10 years for diabetes. I had been complaining loudly and persistently for 2 years or more to my family physician as well as my endocrinologist. FINALLY, 2 months ago, my GP tested B12 levels and it was found to be 114. Now wonder I've been struggling. Am taking 1000mcg per day in addition to a once a month injection of 1000mcg. Not sure if the metformin is blocking absorption of the daily B12. Feeling better but now great. I am planning on a serious talk with the endo next week about getting off metformin. Enough is enough.
Posted by: Nancy | April 3, 2012, 10:23 am
I just started taking Metformin about a month or so ago and within the last couple of weeks I have been feeling extremely exhausted and my hair HAS been falling out. I thought my thyroid was out of whack again but after testing and coming back normal, I am left wondering what is going on. I am going to ask my Endo about the B12 levels. I do take a daily multi-vitamin but not sure if that is enough in this case. Will a vitamin supplement such as Super B Complex (15mcg of B12)be useful in attaining proper levels or does it have to come in the form of an injection or patch? I have PCOS, IR, and Hypthyroid/Goiter. Thank you.
Posted by: Mindy | April 20, 2012, 10:03 am
some years ago after tests I was told I needed to have b12 injections also that my consultant recomended that I stop taking metformin which I had been taking for a couple of years.( I have type 2 diabetis ) this was some years ago, about 3 years ago I saw a different Consultant who prescribed me Byetta and again metformin when I questioned him about this he said that any trouble I had in the past would not now be a problem as the drug had been refined. I hate the b12 inections but I have been told I will have to take them for the rest of my life, can I not be tested to see whether I still have the problem or will it be unsafe for me to stop taking the injections to find if I am in need of b12 injections.
Posted by: jeanette | March 16, 2013, 6:01 pm
I have been taking Metformin from 1999 onward, almost all of my hair has fallen out. I have been sent to a doctor who found no reason. In the last 22 weeks I have been on a medication for a medical condition, that leaves me tied and I have been reallizing I have been this way for years. I am retired and if I can get the dishes once a day I am feeling good. I will see my Dr of 35 years tomorrow and ask for b12 shots and lots of daily. I have been drinking 600% of daily intake in a sugar free energy drink and have felt almost human for the last 2 weeks.
I was never warned of b12 loss but I also understand it may be causing the hair loss. Many people have spoke of Metformin = hair loss due to b12 deficiency. Wish I had known this 10 years ago. Thanks for your article.
Posted by: bev | August 12, 2013, 12:53 pm
This makes perfect sense! I started taking metformin regularly in late April or early May, I forget. I was taking a multivitamin until mid June, when I ran out and forgot to buy new ones. After a week or so, I found I had no energy at all. I wasn't sure what was the source of my lethargy, thought maybe allergies or something... then as it persisted, I thought what has changed? and I remembered that I'd stopped taking vitamins. I started taking them again and bam, I'm normal. I knew there had to be a deficiency, but I wasn't sure what. I know PCOS is supposed to have connections with magnesium and vitamin D, and maybe they play a part too, but I'm guessing it is the B-12 in that B vitamins have such a link to energy.
Posted by: Pamela | August 12, 2013, 4:06 pm
I have been experiencing extreme tiredness for quite a number of years. I have been through some personal turmoil the past 3 years and thought that stress was a contributing factor to my even more declining energy levels. It was not until April 2013 when I as diagnosed with Pernicious Anemia, but was later told that I did not have it. I started getting an extreme heavy feeling in my legs until I was barely able to move and have had very painful stitches in my feet and lower legs. Headaches was a consistent part of my life. Therefore the trip to the doctor and the eventual diagnosis of PA. I did not find the GPs very helpful. None of them ever warned me about taking Metformin for PCOS. I have taken 850mg three times a day with Noriday and Aldactone. In the two months that I was barely able to walk, I started reading up on B12 deficiency. Needless to say that the doctor was very reluctant to prescribe B12 and reluctant for me to have the injections. She nevertheless prescribed it and I have been injected with it since April. I was able to walk again at the end of May but in the process have learned that it might be best to get Beriglobin injections as I also have suffered from flu-like symptoms for many years, such as sore throat, rhinitis, ear infections and low-grade fevers. http://www.mirren.co.za/beriglobin%20p/beriglobinp.html. A light bulb went on as I have had these injections years ago and remember how it boosted my energy. I was unable to get it into my country of residence and have gone to South Africa to get a series of injections. Other countries where it is freely available is Germany and Austria. It is also available online but with a doctor's preion and check if you can get it past customs. If anyone wants to read more about B12 deficiency, check out http://b12d.org/ which is a wonderful site/support group. I also want to mention that a B12 deficiency also influence the iron levels. I am taking 2 Ferro-Tabs (200mg each) once a day with 500mg Vitamin C for better absorbtion. The GP who initially diagnosed me with PA did not help me at all regarding the iron, but only prescribed the tablets. I had to find out for myself that it would be better absorbed if taken with vitamin C. I have heard from the drug store that pineapple is very rich in Vitamin C and will help. I am also taking Magnesium Complex Plus, Fish Oil, Zinc, Selenium and a B-complex. Do know that B12 is only effective when injected. I have learned that too from reading up and by confirming it with the doctor who is now injecting me with Beriglobin and I also getting B12 in addition to boost my immune system. B12 tablets or patches are not effective. I, of my own accord, started taking Metformin 2x a day, instead of 3x per day. I don't know if anyone have been through the same/similar symptoms but I can assure that I already feel better after getting the Beriglobin. I am not saying that this is the ultimate cure but it was worth a shot after having to go through all of the above mentioned. I hope some of the information might be useful to someone.
Posted by: Marlene | September 2, 2013, 4:25 am
I was on metformin for PCOS - i voluntarily took myself off it about 14 months ago, and 2 months ago my b12 was 127ml, iron def, and vit D deficient. Things weren't feeling right which is why i dropped of the met and changed my birth control method. just thought i'd chime in if anyone keeps up with this still.
Posted by: Michele | October 7, 2013, 10:18 pm
Not sure if anybody reads this far in the comments but I wanted to note that if at all possible people should be taking methylated b-12-- this is critical. Many people have genetic mutations that cause their bodies to have a hard time processing standard b-12 into methylcobalamin (active/methylated b-12) and it makes sense that the people feeling b12 deficient easiest are the ones who most need the active form. It is dangerous to have too much standard B12 roaming around your body if you have a MTRR mutation.
Also, be aware of signs of too much B12, which I think are primarily restlessness and anxiety, and adjust your dose as necessary.
Posted by: Jen | March 16, 2014, 3:05 pm
Wow! Now I understand why im so tired, every day and in the morning i feel like a robot my legs feel so stiff my OB had made test on diabetes, thyroid and blood levels and he tells me that everything is ok, yes i have been having problems concentrating, in other words taking B 12 vitamins pills will not be absorb ?? Only if you get the injection??
Posted by: ashley | June 1, 2014, 7:33 am
Ashley, you should have your B12 levels checked. While a B12 injection is best absorbed, you may be fine supplementing with methlyated oral sublingual B12 (under the tongue). B12 injections are usually reserved for those with significantly low B12 levels. Let us know what you find out!
Posted by: Angela Grassi | June 1, 2014, 8:54 am
I was on Metformin for a number of years. I was having trouble with my gut. One to two hours after having a bowel moment I would unknowingly leak out faeces. It got so bad
that I had to use sanitary towels. I was checked out by a gastroenterologist but nothing untoward was found. I also was extremely anaemic. I was put on iron pills and then iron injections and finally a intravenous drip every few days. I was also vitamin B12 deficient. I decided to do some research on the Internet and bingo! Metformin was the cause. I went off it for a few days and the leaking faeces stopped. The dr said it was just coincidence so I took metformin for a few days again and was back to square one. I'm on a different medication at my insistence and I am a different person. I think drs should be made aware of this as I went through a tough time. This shouldn't happen to anyone. Keep well, Jean (68)
Posted by: Jean Strachan | June 2, 2014, 5:55 pm
I have been on metformin 500mg twice a day.I have been on it for about 5 years now. I am the same as soon as I eat maybe 30 min. later running to the bathroom. I have bowel leakage sometimes at night but not all the time. I keep telling my Doctor that I am very tired all the time. It takes everything out of me just to do my daily chores. I am going to ask for a B 12 blood test when I go in to see the Doctor. I was never so tired in my life. This has been going on for so many years. I would love to be outdoors fishing,swimming and playing with my children. I now feel like it is a big struggle just to do this. Thanks for the info
Posted by: Amy | July 23, 2014, 10:55 pm
I wish I'd read this article a month ago. I have PCOS and metabolic syndrome..reactive hypoglycemia, insulin resistance, etc.
My endocrinologist prescribed 1500mg of metformin daily. One 500mg tablet in the morning, 2-500mg tablets in the evening.
I began experiencing horrible neck pain, headaches, and tingling in my fingers..as well as the worst persistent nausea I've ever known.
I was convinced it was my medications (I was prescribed metformin as well as other drugs for treatment for my conditions).
I'd be so nauseated..for DAYS..my neck hurt. My head pounded. My fingers tingled..The nausea was bad enough that I'd stop taking the medicine. My neck stopped hurting. The headache went away..my fingers stopped tingling.
I felt better, so I'd start taking the medicine again.
An xray and two MRI's later..there's NOTHING on the film!! There's nothing structurally wrong..no disk problem, no tumors or any other growths..NOTHING. I was glad, but also nearly in tears of frustration..I still had zero answers.
I had blood drawn at one of my visits with my endocrinologist..I was vitamin D deficient. I didn't know enough to ask about any other vitamin levels. I was prescribed a once-weekly supplement, the level was corrected and that was that.
I'm going to get a second opinion from a different endocrinologist at a different office..that appointment is roughly 2 weeks away.
Then I see this article..
WOW. I'm not sure if my B12 levels are/were low, but I do know that I was taking metformin and suffered neurological problems at the same time.
My last dose of metformin was 2/10/15. I haven't had a headache, no neck pain and ZERO nausea since then.
Thank you for this article. I'm taking a copy with me to the new endocrinologist when I go.
Posted by: Rhonda | March 3, 2015, 2:00 pm
I've been on Metformin since 2004, and taken B12 supplements since about 2008 on and off (whenever it got low), this year doc decided I'm taking it permanently.
Posted by: Bea | March 4, 2015, 4:02 am
I have been taking Metformin 1,500 mg in conjuction with Lo Lo Estrin to treat PCOS for alomost two years. I actually went off them for several months because when taking the medication I would start to feel tired and achy and alomst flu like. I felt better after I went off but of course I needed to go back on. After about 3 weeks back on the medication I started to feel overly tired and sluggish again. My Dr. Still thinks its all in my head...which shocks the hell out of me because up until now she has always been a great Dr., I am currently looking for another GYN to get a second opinion but I was so relieved when I saw this aritcle. I started taking a b12 supplement and I must say that after only a few days I feel better then I have in months.
Posted by: Sara | March 20, 2015, 12:47 pm
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