Metformin Does Cause B12 Deficiency

Allen called me shortly after he read this. I say shortly because he knows I sleep late and he does respect my sleep time. He was surprised that it has taken this long to publish something we have known for a long time. He knew that I would be busy for most of the afternoon and again the following day, but felt this was important enough to remind me of it and ask that I blog about it. Then he asked if I could meet with Ben, Barry, and him on Saturday. I agreed and was happy to do this.

When I arrived, they were waiting for me. Allen had printed a copy for me and asked if I had read it. I told him that I had and would be blogging about it after March 18. Barry said you already have posts that far out and I said yes. Plus, I have three other blogs ready to post and about 18 more topics I want to write in the weeks ahead. Ben said yes, there have been many topics of interest lately. I said I wish I had time to write about all the topics that interest me.

People taking metformin, one of the safest type 2 diabetes medications, for several years may be at heightened risk of vitamin B12 deficiency and anemia, according to a new analysis of long-term data. Allen knows this from first hand experience and others of us know this because our vitamin B12 levels were low and we cannot absorb what we need from the foods rich in B12.

Metformin helps to control the amount of sugar, or glucose, in the blood by reducing how much glucose is absorbed from food and produced by the liver, and by increasing the body’s response to the hormone insulin, according to the National Institutes of Health.

The study used blood samples and the researchers found that at year five, average B12 levels were lower in the metformin group than the placebo group, and B12 deficiency was more common, affecting 4 percent of those on metformin compared to 2 percent of those not taking the drug.

Borderline low B12 levels affected almost 20 percent of those on metformin and 10 percent of those taking placebo.

Average vitamin B12 levels were higher by year 13 than in year five, but B12 deficiency was also more common in both the metformin and placebo groups, as reported in the Journal of Clinical Endocrinology and Metabolism. The down side of being vitamin B12 deficient can mean nerve damage that is severe and may be irreversible. Severe and prolonged B12 deficiency has also been linked to impaired cognition and dementia. It can also cause anemia (low red blood cell count), but fortunately, this condition is reversible with treatment. Another finding of the study was more people in the metformin group were also anemic at year five than in the placebo group.

Humans do not make vitamin B12 and need to consume it from animal sources or supplements. Vegetarians may get enough from eating eggs and dairy products, but vegans need to rely on supplements or fortified grains.

Doctors who prescribe metformin to patients long-term for type 2 diabetes, gestational diabetes, polycystic ovarian syndrome or other indications should consider routine measurement of vitamin B12 levels, the authors conclude.

People who are taking metformin should ask their doctor about measuring their B12 level. Restoring healthy B12 levels is easy to accomplish with pills or monthly injections.

Finally, the study authors say, “The risk of B12 deficiency should not be considered a reason to avoid taking metformin.”

B12 Deficiency, A Silent Epidemic – Part 2

What is vitamin B12 and why do you need it? Vitamin B12 works together with folate in the synthesis of DNA and red blood cells. It is also involved in the production of the myelin sheath around the nerves, and the conduction of nerve impulses. You can think of the brain and the nervous system as a big tangle of wires. Myelin is the insulation that protects those wires and helps them to conduct messages.

Severe vitamin B12 deficiency in conditions like pernicious anemia (an autoimmune condition where the body destroys intrinsic factor, a protein necessary for the absorption of vitamin B12) used to be fatal until scientists figured out death could be prevented by feeding patients raw liver (which contains high amounts of vitamin B12). But, anemia is the final stage of B12 deficiency. Long before anemia sets in, vitamin B12 deficiency causes several other problems, including fatigue, lethargy, weakness, memory loss and neurological and psychiatric problems.

Vitamin B12 deficiency occurs in four stages, beginning with declining blood levels of the vitamin (stage 1), progressing to low cellular concentrations of the vitamin (stage 2), an increased blood level of homocysteine and a decreased rate of DNA synthesis (stage 3), and finally, macrocytic anemia (stage 4).

Vegetarians and vegans please read: vitamin B12 is found ONLY in animal products. Vitamin B12 is the only vitamin that contains a trace element (cobalt), which is why it’s called cobalamin. Cobalamin is produced in the gut of animals. It’s the only vitamin we can’t obtain from plants or sunlight. Plants don’t need vitamin B12 so they don’t store it. A common myth amongst vegetarians and vegans is that it’s possible to get vitamin B12 from plant sources like seaweed, fermented soy, spirulina, and brewers yeast. But, plant foods said to contain vitamin B12 actually contain B12 analogs called cobamides that block intake of and increase the need for true vitamin B12. This explains why studies consistently demonstrate that up to 50% of long-term vegetarians and 80% of vegans are deficient in vitamin B12.

The effects of vitamin B12 deficiency on kids are especially alarming. Studies have shown that kids raised until age 6 on a vegan diet are still vitamin B12 deficient even years after they start eating at least some animal products.

Table 2. Some Food Sources of Vitamin B₁₂

Food	Serving	Vitamin B12 (mcg)
Clams (steamed)	3 ounces	84.1
Mussels (steamed)	3 ounces	20.4
Mackerel (Atlantic, cooked, dry-heat)	3 ounces*	16.1
Crab (Alaska king, steamed)	3 ounces	9.8
Beef (lean, plate steak, cooked, grilled)	3 ounces	6.9
Salmon (chinook, cooked, dry-heat)	3 ounces	2.4
Rockfish (cooked, dry-heat)	3 ounces	1.0
Milk (skim)	8 ounces	0.9
Turkey (cooked, roasted)	3 ounces	0.8
Brie (cheese)	1 ounce	0.5
Egg (poached)	1 large	0.4
Chicken (light meat, cooked, roasted)	3 ounces	0.3
*A three-ounce serving of meat or fish is about the size of a deck of cards.

Only bacteria can synthesize vitamin B12. Vitamin B12 is present in animal products, such as meat, poultry, fish (including shellfish), and to a lesser extent dairy products and eggs. Fresh pasteurized milk contains 0.9 mcg per cup and is an important source of vitamin B12 for some vegetarians. Those strict vegetarians who eat no animal products (vegans) need supplemental vitamin B12 to meet their requirements. Recent analyses revealed that some plant-source foods, such as certain fermented beans and vegetables and edible algae and mushrooms, contain substantial amounts of bioactive vitamin B12 (this is a point of disagreement among the experts). Together with B-vitamin fortified food and supplements, these foods may contribute, though modestly, to prevent vitamin B12 deficiency in individuals consuming vegetarian diets. Also, individuals over the age of 50 should obtain their vitamin B12 in supplements or fortified foods (e.g., fortified cereals) because of the increased likelihood of food-bound vitamin B12 malabsorption with increasing age.

If you are interested in more reading, please read this from Oregon State U and this from the U of Maryland. These are just two of the many sources I used plus talking with two doctors. I could write more, but much of it would be very technical.

B12 Deficiency, A Silent Epidemic – Part 1

This surprised the dickens out of me, I learned how serious vitamin B12 deficiency could be, and yet, many doctors just don't get it. This is just like diabetes as it is hidden and not plainly visible. Granted, I have blogged about vitamin B12 before, but this is done with several weeks of research and from several sources. In addition I have had contact with two doctors that know about the damage vitamin B12 deficiency can cause.

No, vitamin B12 deficiency is not a hidden deficiency, but a deficiency that doctors refuse to recognize and give the priority it deserves. Most doctors just tell patients to eat more meat and replenish their B12 supply. They forget about the intrinsic factor that many of the elderly loose and therefore lose the ability to absorb vitamin B12 from the meat they do consume. Those that are vegetarians and vegans have to take a vitamin B12 supplement because they do not obtain any vitamin B12 from plants.

According to one doctor, vitamin B12 deficiency is described in every medical textbook and the causes and effects are well-established in scientific literature.

First, we need to understand why vitamin B12 deficiency is very common.

The absorption of vitamin B12 is complex and involves several steps, each of which can go wrong. Causes of vitamin B12 malabsorption include:
■ intestinal dysbiosis (An unhealthy change in the normal bacterial ecology of the intestines
■ leaky gut and/or gut inflammation
■ atrophic gastritis or hypochlorhydria (low stomach acid)
■ pernicious anemia (an autoimmune condition)
■ medications (especially PPIs (Proton-pump inhibitors) and other acid- suppressing drugs)
■ alcohol
■ exposure to nitrous oxide (during surgery or recreational use)

This explains why B12 deficiency can occur even in people eating large amounts of B12-containing animal products. In fact, many patients that are vitamin B12 deficient are following a Paleo diet where they eat meat 2-3 times a day.

In general, the following groups are at greatest risk for B12 deficiency:
■ vegetarians and vegans
■ people aged 60 or over
■ people who regularly use PPIs or acid suppressing drugs
■ people on diabetes drugs like metformin
■ people with Crohn’s disease, ulcerative colitis, celiac or IBS (irritable bowel syndrome
■ women with a history of infertility

Vitamin B12 deficiency is far more common than most doctors and the general public realize. Data from the Tufts University Framingham Offspring Study suggest that 40 percent of people between the ages of 26 and 83 have plasma B12 levels in the low normal range – a range at which many experience neurological symptoms. Of these, 9 percent had outright deficiency, and 16 percent exhibited “near deficiency”. Most surprising to the researchers was the fact that low vitamin B12 levels were as common in younger people as they were in the elderly.

Vitamin B12 deficiency has been estimated to affect about 40% of people over 60 years of age. It is entirely possible that at least some of the symptoms we attribute to “normal” aging, such as memory loss, cognitive decline, decreased mobility, etc., are at least in part caused by vitamin B12 deficiency.

What do all of these diseases have in common? This is from another source.

• Alzheimer’s, dementia, cognitive decline and memory loss (collectively referred to as “aging”)
• Multiple sclerosis (MS) and other neurological disorders
• Mental illness (depression, anxiety, bipolar disorder, psychosis)
• Cardiovascular disease
• Learning or developmental disorders in kids
• Autism spectrum disorder
• Autoimmune disease and immune dysregulation
• Cancer
• Male and female infertility
  
  

Answer: they can all mimic or duplicate the signs and symptoms of vitamin B12 deficiency.

Why is vitamin B12 deficiency so under-diagnosed? Vitamin B12 deficiency is often missed for two reasons. First, it’s not routinely tested by most doctors. Second, the low end of the laboratory reference range is too low. This is why most studies underestimate true levels of deficiency. Many B12 deficient people have so-called “normal” levels of B12. Yet it is well-established in the scientific literature that people with B12 levels between 200 pg/ml and 350 pg/ml (It means picograms per milliliter (pg/ml), levels considered “normal” in the U.S., have clear B12 deficiency symptoms. Most healthy people have body stores of about 1200 mcg of vitamin B12.

Table 1. Recommended Dietary Allowance (RDA) for Vitamin B₁₂

Life Stage	Age	Males (mcg/day)	Females (mcg/day)
Infants	0-6 months	0.4 (AI)	0.4 (AI)
Infants	7-12 months	0.5 (AI)	0.5 (AI)
Children	1-3 years	0.9	0.9
Children	4-8 years	1.2	1.2
Children	9-13 years	1.8	1.8
Adolescents	14-18 years	2.4	2.4
Adults	19-50 years	2.4	2.4
Adults	51 years and older	2.4*	2.4*
Pregnancy	all ages	-	2.6
Breast-feeding	all ages	-	2.8
*Vitamin B12 intake should be from supplements or fortified foods due to the age-related increase in food-bound malabsorption.

Help in Diabetes Management Education – Part 10

Part 10 of 12

Goals and how to set them is up to you. Beware of doctors that set the goals for you and will not discuss the reasons or why they are what they are. These paternalistic doctors need to be in control, but do not want you in charge of anything. Never mind that you only see them at most about one hour per year. If you don't make their goals, be prepared for a tongue-lashing. If you want to find out how bad they are, tell them that your goals are different short-term and you will consider their goals long-term. Be prepared to be told to find another doctor.

No, a doctor should suggest goals and give you the reasons, but if you have other ideas, they should listen. If they feel you are not setting the correct goal, they may encourage you to try for a different goal. This means that they are trying to help you, and will listen to you. Suggestions are always appropriate from doctors, until they know you and how hard you work or don't work to attain goals.

I have supplied you with reading to help you set your own goals in the last nine blogs.

Depending on the progress of your diabetes at the time of diagnosis, you might want to consider a goal of getting off medication. This will depend on many factors; the first is whether you have a doctor that will accept this. Second, you will need a plan of action that your doctor approves. Then you will need a food plan that will help keep your blood glucose levels in acceptable range.

Next, make sure that you have an exercise regimen that you will enjoy and are capable of accomplishing. Many fail when it comes to the last two items. You will need to keep testing and seeing the doctor for appointments. The next thing will be whether you are succeeding or having problems. Testing will let you know as will the A1c that the doctor sees. The important thing to realize is if you are having trouble keep your blood glucose levels down that you don't stay off medication for too long.

One of our new members tried three times before giving up when his blood glucose levels kept rising each time. The third time his doctor told him not to try again until he had kept his blood glucose levels below a set level for at least six months on medication and then for another six months at a lower level of medication. His doctor is supporting him and this makes him want to keep trying until he knows it is no longer possible.

Besides goals, people need to understand that as they age, their bodies can stop being efficient enough in obtaining the vitamins and minerals necessary for health from many foods. Most of the time the correct foods will supply everything you need.

People that are on metformin need to be concerned that they are not becoming deficient in vitamin B12. Folic acid (vitamin B9), especially when taken in high doses, can mask the symptoms of a vitamin B12 deficiency. Older and even a few middle age people with type 2 diabetes can become unable to absorb or manufacture vitamin B12 from animal foods. Vitamin B12 is found only in animal foods. Liver, sardines, and salmon rank highest, with liver running away with it. Kidney, eggs, beef, and pork are also good sources. There are no vegetarian sources.

If you develop neuropathy – a tingling or burning in your feet, and especially the toes may indicate that you may have a vitamin B12 deficiency. The quicker you have the test the more likely you will be able to prevent the neuropathy from spreading. Some of our members have had vitamin B12 shots and then prescribed a supplement and a few others have been told to start a vitamin B12 supplement.

The final bit of information on this is your blood glucose levels need to be managed to keep them below 140 mg/dl. With about 60 percent of the people with diabetes developing neuropathy, this tells us that many people are not managing diabetes and may vitamin B12 deficient.

Joint January Meeting

Our January meeting started with Dr. Tom (previously shown as our local doctor) addressing both groups. First, he thanked our group for the impromptu meeting earlier and expressed his thanks to Sue for bringing her relative to be tested and having her depression brought under control without the need for depression drugs. He then turned to his group and told them that thanks to this group including you, many of you will now be tested for different vitamin and mineral deficiencies that would not otherwise be considered deficient.

Next, he explained that the last few months had been intensive and he thanked us for the research we do and to his group, he asked if any of them might be interested in research. Only one person expressed any desire and he was asked to meet with us after the meeting was over.

Tim had been setting up the projector for this Oregon State University website. Dr. Tom said he wanted to start with vitamin B12 and the foods area first within B12. When Tim scrolled to Food Sources, Dr. Tom took time to read it aloud and then emphasized how important the last sentence in the first paragraph should be to everyone. It says, “Individuals over the age of 50 should obtain their vitamin B12 in supplements or fortified foods like fortified cereal because of the increased likelihood of food-bound vitamin B12 malabsorption.”

Then Tim brought up the University of Maryland Medical Center website and scrolled down to the Dietary Sources, which reads, “Vitamin B12 is found only in animal foods. Good dietary sources include fish, shellfish, dairy products, organ meats -- particularly liver and kidney-- eggs, beef, and pork.” Dr. Tom said he understands people that do not like organ meats, as they are not his favorites either. He thanked Tim for doing this as he felt both sources were important. Tim stated that both URLs would be included in the email sent about the meeting.

Dr. Tom then explained that for anyone over the age of 50 that might have fatigue or other problems discussed on either site should not be afraid to ask for the test to determine if they might have a deficiency. He would do the test and felt it was important for people to consider before doing anything about supplements. Then he emphasized that this was important for their doctor to know because of the medication conflicts between vitamin B12 and certain prescription medications, as shown at the bottom of my blog..

After some discussion, Dr. Tom called attention to the Age-Related Macular Degeneration section and told people to read this on both sites. Then he introduced the ophthalmologist and said he would talk about vision and some of the common problems for people with diabetes.

The eye doctor thanked Dr. Tom and then thanked me for inviting him to speak about problems for diabetes affecting eyesight. He explained that I had provided him with my blog on vision and the related websites and this helped explain much of what he would be covering. Next he asked if everyone had diabetes or pre-diabetes. All hands went up and he asked how many had their eyes checked within the last year. Only 16 kept their hands up. He asked if there were some that had eye exam in the last two years – only two.

Then he addressed the seven that had not raised their hands asking how many of them were on Medicare and four raised their hand. He then stated that the American Diabetes Association guidelines stated that two years was now the recommended time between appointments. He said this is not good and you should see your eye doctor for a dilated eye examination at least annually if you are over 50 years of age and annually if certain conditions exist before age 50. With some eye problems, an exam every six months is recommended.

He then asked Tim to start the slides, which showed the eye, and he pointed out what he would be able to see in a dilated eye exam. Some of the slides showed what age-related macular degeneration (AMD) looked like. Then he moved on to cataracts and had several slides showing different aspects of their development. Then he had slides showing what glaucoma looked like. He then concluded with retinopathy and how this looked in the eye exam.

He concluded that of those present, that were his patients, none had retinopathy, several had early stages of cataracts, two were being treated for AMD, and only one had early glaucoma. He then had Tim show the last three slides, which showed advanced glaucoma, cataracts, and AMD. Anyone with these stages can be diagnosed as legally blind. The good news is by discovering them early; treatment can prevent this from happening or delay the serious problem of blindness.

He concluded by saying everyone over the age of 50 should have a dilated eye exam on an annual basis if they have diabetes. Medicare does cover most of the cost and will pay for most treatments. He finished that his office will work with people that are not covered by insurance and do their best for them in getting them help. Discussion and questions followed and he took a few people aside to talk privately with them. The meeting ended and the Dr. Tom asked several of us to talk with the one interested in doing research.

The eye doctor asked if I would be writing more blogs on the eye diseases and I said I was thinking seriously about this. Since he has my address and email address he asked which format I would prefer. I said email if he didn't mind. He indicated that he had several URLs that he would send me and if I could use them he would send several images as well. We agreed and the meeting was over.

Another Impromptu Meeting Asked by Our Local Doctor

Early this afternoon, I received an email asking if I would attend an impromptu meeting to discuss what needed to be done as a doctor would not test for Vitamin B12 or any vitamin or mineral deficiencies. One additional comment was included asking a few of us to research what the American Diabetes Association (ADA) said about this in their guidelines.

Since I have been studying the new 2014 guidelines since I discovered them on December 31, 2013, I knew there was nothing to be found. I went to the American Association of Clinical Endocrinologist (AACE) site to see if there was anything that I hadn't read before, but again nothing about testing for deficiencies. I knew there would be articles in Medscape and other places, so I called on my search engine to help me find them.

Success! I even located one reference on the ADA site, but not part of the guidelines.

The percentage of people with type 2 diabetes taking metformin and developing vitamin B12 deficiency varies from 6 to 52 percent depending on the study. I quickly sent off the URLs to Tim since he would have his laptop at the meeting. Then I copied and printed several points to have at the ready from the ADA and included the following - “Several researchers have made recommendations to screen those with type 2 diabetes on metformin for serum B12 levels. However, no formal recommendations have been provided by the medical community or the U.S. Prevention Services Task Force.”

Ten of our members were present and talking before the doctor arrived. He was upset and we could tell this. He apologized to Allen and stated that this meeting should not have been necessary. He had thought that he had been convincing enough in his presentation to the doctor Allen had trouble with about vitamin B12 deficiency. The doctor then explained that at noon, he had received a call and was told that the ADA did not have anything in the new guidelines about testing for vitamin B12 deficiency and as such, he was not going to test. He did not feel the cost, though small was worth the small percent of people that would be deficient.

Tim took over and said that he had several good articles and that I had a handout from the ADA site for another article not part of the ADA guidelines. I handed out my print out and pointed out the information I have in red above. Allen was surprised at this, and asked why no one would take responsibility for testing. The doctor said he was and that some other doctors would be testing. He asked if Tim could put up the article from ADA and Tim said it would be shortly.

After Tim had the article up, he scrolled down to this. “Although classical B12 deficiency presents with clinical symptoms such as anemia, peripheral neuropathy, depression, and cognitive impairment, these symptoms are usually absent in those with biochemical B12 deficiency.” The doctor had to ask how many knew about this and 7 of those present put their hands up. He said it is no wonder you people do research. He said he was aware of anemia, depression and cognitive impairment, but not the other two symptoms. He added this is the reason he asked for the impromptu meeting as even he could learn.

Allen spoke up and said the individual he brought in was complaining about neuropathy and that is why he thought he could be B12 deficient. He said that was also the reason he had been taken to see the endocrinologist. He was also anemic at the time. Tim stated that we try to inform our members about this and make sure, if they are on metformin for any length of time, that they are tested.

After more discussion, Tim pulled up the article from WebMD and this generated even more discussion. The doctor commented that with these two articles, he wonders why the ADA will not take a position about testing for B12 deficiency. He said he now appreciates our group even more with this meeting and the information we were able to provide. He asked one final question about whether he should consider testing the elderly, above the age of 65 for B12 and vitamin D. Several of the group answered yes, but he noticed I had not answered so he turned to me.

I said that was a difficult question. I would answer yes for anyone with diabetes, but this would be a judgmental call on his part for people without diabetes. He said if he started at age 70, would I change my answer. I said that first he should asked the patient if he/she was taking separate vitamin B12 and D supplements. If they were, he would need to ask questions about neuropathy and he would probably need to explain what neuropathy or peripheral neuropathy was. He would also need to ask if any other doctor had tested for these.

I said if this was also part of the annual exam, then the tests could be done as part of this and then only annually if they were in the lower part of the accepted range. I said that if cognitive impairment or any of the other symptoms were suspected, then yes, do the tests.

The doctor then thanked everyone for attending and asked if there were any questions. Receiving none, he asked Tim to send an email with the URLs and a copy of the summary of the meeting to him. With that, the meeting ended.

Again, a Doctor Refuses to Test for Vitamin B12 Deficiency

Allen called Friday morning in a panic. He said that a friend of his could not get tested for vitamin B12 deficiency. He was seeing the same doctor Allen had his trouble with. Allen wondered if he should take his friend to the endocrinologist we see or take this up with the local doctor. He said his friend had been taking metformin longer than he had.

I suggested that he try the local doctor and see if he was sincere in the concern he had expressed earlier. Allen said this was what he was thinking and said he would call me back later. That afternoon he called and said the doctor had taken him immediately and did several tests like the endocrinologist had done on him. Allen said that his vitamin B12 level was even lower than his had been. His vitamin D level had been slightly higher than Allen remembered his had been. Then Allen said the doctor had also checked the potassium and magnesium levels and they were low.

Once the doctor had the test results and found out why he had not been tested by his doctor, Allen said he had called the doctor and made his results known and told the doctor to be in his office that evening. Allen said he then called the pharmacy to see what they had for potassium and magnesium supplements and wrote a note for him to purchase the supplements and take one a day for 30 days and he would be retested then.

Then Allen was asked to leave the room while he gave vitamin B12 and D shots. In the discussion when Allen was back in the room, the doctor asked his friend not to drive until his levels were back in the normal range. He then asked Allen to let him know if he did drive and he would ask for his license. He was scheduled for shots in the next two weeks and then he would be tested again the third week before they decided whether he needed more shots. He would be started on vitamin B12 and D supplements at that time if no more shots were required.

Allen said that he was asked to stay while his friend checked out. The doctor had thanked him for bringing his friend and said that this would go a long way in helping him convince this doctor that many people could not eat their way to good health and levels of vitamin B12 on metformin. I told Allen that I had sent the URLs for this article and this article to the doctor and received a thank you for sending them. Allen asked me to send them to him as well.

Allen said his friend wanted to drive, but Allen said the doctor was serious and recounted what had happened to him. Allen said he had also alerted his friend's daughter about the situation and she had agreed to help her father until this was over.  I asked Allen how old his friend was and Allen said only a year younger than he was.

Allen anticipated my next question and stated that he was on VA assistance and that he had been warned about his vitamin B12 levels, but had ignored them. I said he may not have been very low or they would have given him a shot then.

Allen said his friend had asked him to drive for his tests the following week at the VA and then for his appointment the week after. I said that he may be taking them serious now, but at least he knows. I commented to Allen that he could send out an email to everyone now and emphasize to people the importance of being tested for vitamin B12 especially if they had friends or relatives on metformin. Allen thanked me for allowing him to do this and he would have Tim send it on to people in the other groups.

Allen concluded by saying he had asked his friend to consider joining our support group, but his friend was not sure he wanted to. Allen said he was not going to pressure him, but would continue to promote the idea with him.

Metformin – Is This First Line Medicine Safe?

This is the substance of an article published in the April issue of Diabetes Care. The title they use is “Diabetes Prevention With Metformin Is Safe, Well-Tolerated.” In essence this is correct, but only when other vital information is added which is absent from the details of this study. A pharmacist friend very kindly pointed this out to me in an email.

She stated, “Metformin can for many (but not all) individuals cause a Vitamin B12 deficiency. Unless they consume foods high in Vitamin B12, most people will end up having this deficiency in long-term Metformin use.” Even my own endocrinologist suggested adding a Vitamin B12 supplement to my regimen while on Metformin. I am thankful I listened to her. I was not Vitamin B12 deficient, but I was at the low point in the recommended range.

Based on my experience, I would suggest anyone taking Metformin (glucophage) talk with their doctor about having the Vitamin B12 test done to establish a baseline and a discussion about adding Vitamin B12 at some point. I repeat, this should include anyone taking or adding metformin to their medication regimen. This is one area that I now feel strongly enough about to repeatedly urge people taking metformin to have the vitamin B12 test done. 

A little background into the symptoms of vitamin B12 deficiency shows they are the classic fatigue and anemia. Most doctors will not do this test, “because the 'Standard of Care' is to ONLY do Vitamin B12 Testing if a patient has a condition called Macrocytic Anemia- where red blood cells become large and shows up as a high number on the MCV Blood Test that is part of a Complete Blood Count. This is somewhat arbitrary and stops many tests that could prevent severe vitamin B12 deficiency.

This article from WebMD dated June 8, 2009 is the article my pharmacist friend suggested that I read. Yes, it is a very convincing argument for being screened for vitamin B12 deficiency. In the study, 40 percent of type 2 diabetes patients using metformin had vitamin B12 deficiency or were in the low-normal range for vitamin B12. Of 77 percent of metformin users with vitamin B12 deficiency also had peripheral neuropathy. This is a common nerve damage complication associated with type 2 diabetes.

Peripheral neuropathy is a major complication of diabetes, as such, the researchers suggest that people using metformin be screened for vitamin B12 deficiency or supplemented with vitamin B12. They further stated that anyone already diagnosed with peripheral neuropathy that uses metformin should be screened for vitamin B12 deficiency.

Vitamin Deficiency Anemia

Since Allen ended up on the deficient side for Vitamin B12, we have been doing a lot of research about the signs, symptoms, and causes. We have found quite a bit of information. First, from the Mayo Clinic is their article on vitamin deficiency anemia, which covers the tests Allen was fortunate that the doctor did do. He was at the low point on folate, very low on vitamin B-12, and low normal range for vitamin C.

The doctor did tell him to add a daily men’s supplement to his regimen and make sure that he added a vitamin C to his regimen. The doctor told him that the prescription levels of vitamin D and vitamin B12 would be for a month only and then he should purchase the supplements in any store and set the lower limit at the level he ordered until the completion of the next tests. Allen commented that this was good to know and that he was surprised that the doctor was concerned about his supplements. Both Tim and I said that was a good thing and that he would probably continue to test for these until his body maintained them in the recommended range.

We did discuss this and three of our members said they were going to ask their doctor to run the same tests. We also pulled up several listings of what foods were high in the vitamins and some minerals. Allen now has his license back and feeling much more active. He did decide to use insulin after we presented him with several articles and did a lot of discussion. He did ask if he might be able to drop back to oral medications and we all agreed that could be a goal if he wanted it, but that may not be what he needs for the long term.

After we covered many of the myths about insulin, even Ben admitted that his blood glucose management was so much better; he doubted he would consider going back to oral medications. Ben also has decided to change doctors so that he could be tested for vitamin shortages. We all have been reading about vitamin B12 and several things we could do. Vitamin B12 deficiency is a risk for neuropathy, and several other health problems.

Since the Mayo Clinic article lists the signs and symptoms of vitamin deficiency anemia, we decided to study the article with care. They list the following signs and symptoms:

• Fatigue
• Shortness of breath
• Dizziness
• Pale or yellowish skin
• Swollen tongue that may appear dark red
• Weight loss
• Diarrhea
• Numbness or tingling in your hands and feet
• Muscle weakness
• Irritability
• Unsteady movements
• Mental confusion or forgetfulness

All of us could recognize something in the list that fits us and so the discussion would continue. Everyone agreed that if their doctor would not test them for the same tests that Allen had, they would be changing doctors. Ben is back with the VA and he and Allen both have had their appointments scheduled. Allen is happy since this will help get his insulin much cheaper and they have moved his appointment up to the middle of May. Even Barry is now set up for an appointment locally after his move and his records are now here.

We discussed vitamin B12 foods that would help prevent the deficiency. Most were not aware that much of the vitamin B12 needed could be obtained from eggs, milk, cheese, yogurt, red and white meats, shellfish, and some fortified foods. This was a discussion that opened some eyes and at the same time led to a discussion of low cholesterol and low fat. Tim took over in this discussion about the importance of lower levels of carbohydrates, medium protein and fat since there was much resistance to higher cholesterol and fat.

Brenda did surprise us when she spoke up and said Tim was right and that she had been following this food regimen for several years and her tests showed that the food ratio of carbohydrates, protein, and fat of 20 percent: 30 percent, 50 percent had not caused her test results to increase and that she was actually having better test results and had lost a few pounds. She said she would provide the test information to anyone needing confirm this. She continued by saying that her sister, a nutritionist, had worked with her for the last five years and could also discuss this with anyone needing guidance.

This took a lot of the argument out of the discussion and we moved on to other causes of vitamin B12 deficiency. We pulled up the article by the Mayo Clinic and since no one has had gastric bypass surgery, Crohn's disease or celiac disease, or other problems that interfere with absorption of the vitamin B12, we moved to discussion of the intrinsic factor as vitamin B-12 deficiency is most often due to a lack of this substance.

Intrinsic factor is a protein secreted by the stomach that joins vitamin B-12 in the stomach and escorts it through the small intestine to be absorbed by your bloodstream. Without intrinsic factor, vitamin B-12 cannot be absorbed and leaves your body as waste. Lack of intrinsic factor may be due to an autoimmune reaction, in which your immune system mistakenly attacks the stomach cells that produce it. Vitamin B-12 deficiency anemia caused by a lack of intrinsic factor is called pernicious anemia.

Vitamin B12 is important not only for the production of red blood cells, but also for a healthy nervous system. Vitamin B12 deficiency can lead to neurological problems in neuropathy, mental confusion and forgetfulness. This tells us how important vitamin B12 is for healthy brain function.

Allen joked that he did not want to be the cause of all this learning, but felt that our insistence of his being tested had helped all of us and he had learned a great lesson about nutrition.

We agreed that we may have found a good article to use as our center of discussion, but that we all had learned and needed to learn more. I thanked Tim and Brenda for leading much of the discussion. Brenda said that was why she wanted to be part of this discussion as this was what she had gone through several years ago and realized we were serious about discussing it. She knew some things had changed and she wanted to learn more if possible and she had.

We also gave this article to everyone for reading. It is from WebMD and is very specific to vitamin B12 deficiency.