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Methylation causing hypoglycemia?

Hi folks, this is my first post here. I have started a methylation protocol, and I am getting hypoglycemia in the afternoon and at night (60-70 mg/dL). At first I thought it was hypokalemia, increased my potassium intake, but eventually ended up throwing up in the ER. I have been getting some great improvements from methylation, but the low blood sugar is really a drag.

The background

I am in my early 30s and I have had minor symptoms of chronic fatigue or fibromyalgia my whole life. Allergies, brain fog, muscle knots/pain, repetitive strain injury, eyestrain, skinny, difficulty building muscle, unrefreshing sleep, upper airway resistance syndrome, cold hands/feet, constant thirst. MTHFR 677 +/-, MTRR A664A +/-, bad BHMT. Luckily, I have been able to have a decent career, and I can lift weights and run. But my quality of life is not great.

My protocol

Based on the @Freddd protocol.

Methylation: methylcobalamin 1000mcg-1500mcg, adenosylcobalamin 1000-1500mcg, methylfolate 400mcg, l-carnitine fumarate 250-500mg, Seeking Health B Minus complex 1-2 / day

Vitamins: C, D, E, K, nicotinamide riboside, NADH (discontinued), spirulina

Minerals: Thorne pic-min complex, magnesium 200-300mg, calcium

Other: Phospholipids, R-ALA, milk thistle, fish oil, lysine, gynostemma, ashwaganda

Diet: Mostly meat, whey protein, olive oil, fruit, and sometime small amounts of rice.

The story

Going on the methylation protocol has resulted in either consistent or temporary improvement in most of my symptoms. Sleep is more restful, eyestrain is nearly gone, muscle knots improved, increase in strength, increase in energy some days, decrease in allergies some days.

  • From day 3 of the methylation onwards, when I added methylfolate, I’ve experienced startup symptoms involving lightheadedness. I believed that this was hypokalemia that @Freddd talks about, so I increased my potassium intake.
  • My muscle knots miraculously released
  • I was still dealing with startup symptoms (beating heart, clammy hands, tunnel vision), so I increased my dosage of potassium, decreased the dosage on my protocol, and used diluted electrolyte supplements in water. I ended up throwing up in the ER, likely due to excessive potassium (because I had the reaction right after chugging a lot of potassium).
  • I lost 5 lbs.
  • Having difficulty recovering, and experiencing reactive hypoglycemia on most days and nights. I eventually figured this out with a finger prick device. My blood sugar has been as low as 57 mg/dL. The feelings of hypoglycemia feel exactly the same as my startup symptoms. This leads me to believe that I had hypoglycemia that entire time. I can’t rule out hypokalemia, but my dosage of potassium should have made me get better if that was the main problem (instead of making me throw up). And I have direct proof of the hypoglycemia.
According to my reading, getting hypoglycemia from methylation doesn’t make any sense. If anything, methylation should be making blood sugar control better. I have never had hypoglycemia before (maybe once a year in retrospect), and normally I can eat any amount of carbs or sugary drinks.

What is going on?

Clearly the methylation has changed something in my glucose / insulin / glucagon metabolism. Had some good days where I had a lot of energy and was bounding around. My body felt accelerated by 20% doing everything. I was also lifting weights as usual, before I recognized the hypoglycemia.

I have been trying a bunch of different dietary or supplement changes to address the hypoglycemia, and I’ve had some days without it. I am doing the obvious stuff, like not eating carbs by themselves, reducing whey protein, and eating multiple small meals. I still get blood swings every couple hours, or sometimes, even more often.

The ER visit didn’t help anything, but I’m pretty sure that I was was getting the hypoglycemia as a startup symptom prior to the ER, and then tried to “fix” hypoglycemia with high dose potassium.

I have tried increasing my fat intake, olive oil, MCT oil and butyrate, but no noticeable difference. Chromium 100mcg was already in my trace minerals.

Next I am trying: more soluble fiber (previously at <5g), glucomannan, uncooked corn starch, and l-alanine.

(No need to attempt to answer all of them.)
  • Any theories about what might be happening?
  • Anyone else dealt with hypoglycemia in the context of methylation? I see a few mentions from searching, but they are sparse.
  • Any other ideas for treating the hypoglycemia?
  • Is it more likely that I am dealing insulin resistance or insulin sensitivity?
  • I am holding my methylation at 1000mcg methylcobalamin, 400mcg methylfolate, and B-complex. I am afraid to go higher because last time I increased the methylfolate, the hypoglycemia regressed. Any changes to the protocol that might help?
My methylation results have been great so far other than this and hopefully I can get back on track soon. Thanks!


Senior Member
Pacific Northwest
PicMins contains chromium which might impact your blood sugar.

Also, while your nutrient proticol sounds very good, its important to consider your actual nutrient status and environmental factors rather than just treating SNPs.

You might consider nutrient testing, like a Genova Diagnostics NutrEval, to verify that your body needs all those nutrients in the ratios your taking them in. I've seen many surprises show up with testing.

Starting a methylation protocol can promote your body to mobilize and eliminate heavy metals. Sometimes these don't get completely eliminated but get reabsorbed, causing symptoms, including altering your chemistry and glucose levels. (I got an arsenic rash at one point...)

That all said, from what you've described of your diet, it could just be a little too low carb for you. Adding in beets, carrots, sweet potatoes, legumes, or fruit may be useful.
Thanks @Little Bluestem, @Learner1. Increasing carbs did help. My previous carb intake was probably 40-80g after coming out of a cut from weightlifting. The methylation protocol increased my metabolism, but it looks like my body couldn't keep up.

I stabilized my blood sugar by going up to 100-150g of carbs, and eating carbs, protein, fat, and soluble fiber with each meal. (Previously I had nearly 0 soluble fiber.) Chia seeds in shakes have been great for fiber.

However, I am still not back to normal. I developed a new set of symptoms:
  • Dizziness, poor coordination, and sometimes muscle weakness for 50-90% of the day. Muscle weakness mostly gone now.
  • Thirst, even more than usual
  • Tired eyes (more than usual)... probably due to eye muscles also being weak and not standing up to normal use
  • Sometimes low heart rate and minor heart palpitations in the evening
I've had some degree of these symptoms for the past couple weeks. What I've tried:
  • Drinking more water, increasing sodium, and increasing other electrolytes, either supplemental or from food. It helps, but the dizziness doesn't quite go away.
  • Got blood test. My electrolytes are all at the bottom of the normal range.
  • Going back on small doses of methylation supplements, or cutting them out entirely. Methylation doesn't help the dizziness, and might make it worse (though I am afraid to increase the dosage and find out).
What could be going on?
  • A combination of all the stressors I've dealt with over the past month?
  • Dehydration? I already drink tons of water and I've been drinking more
  • Electrolyte imbalance? Increasing electrolytes hasn't made the symptoms go away completely
  • I am taking calcium and a vitamin K complex. Could either of those result in dizziness? Benign position vertigo is considered to be caused by calcium crystals in the inner ear. If so, then cutting calcium and increasing magnesium should help.
  • Could I be having cerebral perfusion issues? I was dealing with high epinephrine for weeks during the reactive hypoglycemia.
What I am taking now: Trace minerals, nicotinamide riboside, Vitamin C, calcium hydroxyapatite, K complex, Vitamin D, iodine, phospholipid complex, Himalayan sea salt, milk thistle, sometimes potassium or magnesium
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Senior Member
Pacific Northwest
Electrolyte imbalance can cause a lot if interesting symptoms. You may not be taking enough magnesium. Maybe use magnesium malate, up to bowel tolerance? You need it for methylation. Maybe 800mg-1g?

You could be mobilizing something toxic which can produce symptoms...arsenic, lead cadmium, mercury?

How did you choose the calcium? I find Garden of Life Plant bases calcium is a good one.

How are aldosterone, ADH, and all hormones?

I think you need to find a functional medicine doctor to help you. Sounds like you have a lot going on. Where are you located?
Hi @Tyler K, I know it's been a while now how did you progress?

Did you make any progress with these symptoms? I believe my symptoms were much the same and I'm currently experimenting with cutting out all methylation supplements for the past 10 days including B-Complex. 2 small 200mg doses of TMG each seem to have caused some day-to-day methylation stabilisation and even caused some over-methylation symptoms.

I'd be interested to compare further notes if you're still available. My introductory post can be found here.