FAQ Episode 61: For diabetics with migraine: The metformin/B12 connection.

Frequently Asked Questions about Natural Migraine Relief

This post is quite specifically for 1) diabetics, with 2) migraine headaches, who are 3) considering or already taking the oral drug metformin to manage their blood sugars.

Metformin is often the first-line treatment for Type 2 diabetes as recommended by both the American Diabetes Association (ADA) and the American Association of Clinical Endocrinologists (AACE.) In a study of almost 18,000 people diagnosed with type 2 diabetes between 2012 and 2017, 89% were initially prescribed metformin as monotherapy (as their first and only drug.)¹ 

Metformin has several functions. It helps to control your blood sugar by:

• decreasing the amount of glucose you absorb from your food.

• decreasing the amount of glucose made by your liver.

• increasing your body's response to insulin.

Despite its benefits, metformin at higher doses and with longer term use can significantly reduce your Vitamin B12 levels². And reduced Vitamin B12 can play a key role in migraine expression for some individuals.

The absorption and management of B12 in the body is complex, including pathways in both the gut and the liver. Metformin can alter these as follows:

• it can reduce intrinsic factor in the stomach. This protein is essential for B12 absorption. Intrinsic factor levels drop as we age, so this problem can be additive for middle-aged diabetics.

• it can alter small bowel motility, which can inhibit B12 absorption.

• it can alter absorption of B12 via biles salt levels in the gut.

• it can alter how the liver accumulates and manages B12.

This metformin effect is most pronounced with higher doses (>2000 mg/day) and longer term use (>4 years) of metformin.

Let’s review briefly the importance of B12 in those with migraine:

1. Multiple studies have shown that those with migraine are already low in Vitamin B12 levels³⁴⁵ A 2022 study found that low vitamin B12 levels increased the likelihood of chronic migraine 3.6-fold.⁶

2. B12 is one of three B vitamins essential in clearing homocysteine. Excess homocysteine can promote inflammation as a factor in migraine expression.

3. B12 plays important roles in nerve repair, both in central and peripheral nerves.

4. B12 is a key cofactor in cellular energy production. This is one of the reasons that “feeling weak and tired” leads the list of B12 deficiency symptoms.

B12 considerations for everyone with migraine

• consider getting a B12 level. I would encourage you to aim to be in the top half of normal range (~200-900 pg/ml at most labs.) If you are low or on the low side, you can use a 1000 mcg sublingual B12 dose daily as supplementation and recheck the level after 90 days.

• consider having your homocysteine level checked. If its more than 12 mcmol/L, consider taking a combination of methylated Bs (methylB12, methylfolate and pyridoxyl-5-phosphate (methylated B6) as a supplement. Life Extension makes a good combination known as Homocysteine Resist, as one cap daily to start. Recheck the homocysteine level after 90 days of supplementation to assess response. You should aim for a level <10.

If you have migraines and take metformin.

Metformin can be a very useful drug for many with Type II Diabetes. Note that the concerns addressed above were primarily for those on higher or longer term metformin dosing schedules. Its interference with Vitamin B12 does highlight how at times drug side effects or interactions with non-drug entities like vitamins are not part of the drug approval process. Because most practitioners see diabetes and migraines as two separate entities, connections like this can be overlooked.

If you take metformin routinely, have your B12 level checked, both now and yearly. Consider taking a B-100 complex vitamin (or the equivelent in your daily multi) on a regular basis, even if your numbers are a “good normal” level (500 pg/ml or better.) Also, follow the advice above regarding homocysteine.

Its all about synergy

We should keep in mind that almost all health problems, and certainly migraine headaches, have several interlocking root cause factors that conspire to “overfill your glass” and produce its clinical expression as a migraine event. The more of these contributing factors we can find and minimize, the more likely we can contain the migraine event to below the clinical threshhold. Fewer migraines = less pain = less disability. What’s not to like about that?

I wrote my online course Natural Migraine Relief for Women to find and address your unique root cause factors for migraine. Its one-of-a-kind Migraine Action Plan helps you to find and manage the underlying migraine promoting factors most specific to you. For just $7/month (you can easily unsubscribe at any time) subscribing members to this blog have unlimited access to all 26 lessons along with the Migraine Action Plan. See the post The Natural Migraine Relief for Women course: Table of Contents or FAQ Episode 42: What can I learn from the Natural Migraine Relief course? for all the details.

Coming up next: FAQ Episode 62: PTSD and Migraine. You can have PTSD and migraines independantly. This post will consider how the two are related and what you could do to minimize the PTSD related impact on migraine. We will review cause and effect relationships that could suggest mutually beneficial therapies.

1. First-line pharmacotherapy for incident type 2 diabetes: Prescription patterns, adherence and associated costs. David J. T. Campbell, et. al Diabetic Medicine 16 June 2023 https://doi.org/10.1111/dme.14622 https://onlinelibrary.wiley.com/doi/abs/10.1111/dme.14622

2. Metformin-Induced Vitamin B12 Deficiency in Patients With Type-2 Diabetes Mellitus Aakriti Tiwari , et. al. Cureus 2023 Oct 26;15(10):e47771. doi: 10.7759/cureus.47771 https://pmc.ncbi.nlm.nih.gov/articles/PMC10688235/

3. Metabolic and genetic risk factors for migraine in children. Cephalalgia. Bottini F, et.al. 2006 Jun;26(6):731-7.

4. Headache and biomarkers predictive of vascular disease in a representative sample of US children. Archives of pediatrics & adolescent medicine. Nelson KB, et.al. 2010 Apr 5;164(4):358-62.

5. Serum vitamin B12, folic acid and ferritin levels in patients with migraine. Turkish Journal of Neurology. Acar A, et.al. 2011;17(2):090-5.

6. A study on the correlation between pain frequency and severity and vitamin B12 levels in episodic and chronic migraine Sibel Üstün Özek  Arq Neuropsiquiatr 2022 Jun;80(6):586-592. doi: 10.1590/0004-282X-ANP-2021-0192.