Methylation supplements treat insulin resistance

[Gondwanaland]

People who eat lots of vegetables should eat them with enough fat (methyl donors) such as extra virgin olive oil on the leafy greens or butter to broil vegetables.

J Nutr. 2011 Mar;141(3):531-4. doi: 10.3945/jn.110.130369. Epub 2011 Jan 26.
Nutritional genomics: defining the dietary requirement and effects of choline
It is important to recognize differences in dietary requirements for choline in women, because during pregnancy, maternal dietary choline modulates fetal brain development in rodent models. Because choline metabolism and folate metabolism intersect at the methylation of homocysteine, manipulations that limit folate availability also increase the use of choline as a methyl donor.

The supplement folic acid is a synthetic, inactive form that requires more methyl donors to be activated than food folate.

Having said that, an experiment on rats showed that high dose folic acid (without the needed accompanying methyl donors) during pregnancy caused insulin resistance in the offspring.

Journal of Endocrinology
Excess perigestational folic acid exposure induces metabolic dysfunction in post-natal life
The results of this work indicate that perigestational high folic acid exposure the affects long-term metabolic phenotype of the offspring, predisposing them to an insulin-resistant state.

J Nutr. 2010 Jun;140(6):1162-6. doi: 10.3945/jn.110.122044. Epub 2010 Apr 14.
Dietary choline reverses some, but not all, effects of folate deficiency on neurogenesis and apoptosis in fetal mouse brain
In mice, maternal dietary folate, a cofactor in 1-carbon metabolism, modulates neurogenesis and apoptosis in the fetal brain. Similarly, maternal dietary choline, an important methyl-donor, also influences these processes. Choline and folate are metabolically interrelated, and we determined whether choline supplementation could reverse the effects of folate deficiency on brain development

A study in humans showed that folate and B12 supplementation reversed metabolic syndrome, improving insulin sensitivity and lowering homocysteine

Eur J Endocrinol. 2004 Oct;151(4):483-9.
Insulin resistance and endothelial function are improved after folate and vitamin B12 therapy in patients with metabolic syndrome: relationship between homocysteine levels and hyperinsulinemia
Folate and vitamin B12 treatment improved insulin resistance and endothelial dysfunction, along with decreasing homocysteine levels, in patients with metabolic syndrome, suggesting that folic acid has several beneficial effects on cardiovascular disease risk factors

I think that the insulin sensitivity has been completely overlooked on this forum, along with blood cell synthesis. People take huge amounts on folate and B12 ignoring that it can cause hypoglycemia and acidosis, plus it will promote the recruitment of other B vitamins and minerals for blood cell synthesis. Additionally, the B vitamins and minerals which can be quickly depleted by an unbalanced supplementation are involved in hormonal and neurotransmitter balance.

A study has been posted by someone else before showing that unmetabolized folic acid can build up, blocking the use of active folate.

This causes or worsens B12 deficiency and insulin resistance, causing epigenetic changes and predisposing the offspring to IR and obesity.

© 2008 American Society for Clinical Nutrition
Is folic acid good for everyone?
In humans, increased folic acid intake leads to elevated blood concentrations of naturally occurring folates and of unmetabolized folic acid. High blood concentrations of folic acid may be related to decreased natural killer cell cytotoxicity, and high folate status may reduce the response to antifolate drugs used against malaria, rheumatoid arthritis, psoriasis, and cancer. In the elderly, a combination of high folate levels and low vitamin B-12 status may be associated with an increased risk of cognitive impairment and anemia and, in pregnant women, with an increased risk of insulin resistance and obesity in their children.

In my personal interpretation, excess of methylfolate intake can have the following adverse outcomes in regards to insulin resistance:

- first methyfolate can make one who doesn't have IR hypoglycemic, causing panick attacks, acidosis, mood swings etc

- secondly, excess methyfolate will build up and create/worsen insulin resistance, leading to a huge need for potassium (and B1, choline and magnesium).

J Physiol Biochem. 2015 Dec 3. [Epub ahead of print]
The role of dietary potassium in hypertension and diabetes
...
Furthermore, accumulating epidemiological evidence from, especially, the last decade relates low dietary potassium intake or serum potassium levels to an increased risk for insulin resistance or diabetes.
...

I will be happy to discuss it.

PS to check for IR one needs the blood tests of fasting insulin, fasting glucose, insulinemic curve and HbA1c

 

[Gondwanaland]

Also, I would like to add that some sites for diabetics have warnings about high homocysteine, which will be raised by insulin resistance. High homocysteine has a series of implications, especially cardiovascular. I had a vein rupture followed by thormbosis and from the several doctors I saw back then no one asked for homocysteine or insulin blood tests. I am sure I had diabetis insipidus at some point, even though I described my symptoms to Gyn, Endo, Vascular, Hematologist, they never bothered to make a diagnosis from what I described.

 

[Gondwanaland]

BTW Niacin helps because it antagonizes methyl groups by increasing insulin resistance

Long-term niacin treatment induces insulin resistance and adrenergic responsiveness in adipocytes by adaptive downregulation of phosphodiesterase 3B

Also

https://examine.com/supplements/vitamin-b3/
Niacin is an essential B-vitamin. Supplementation results in improved cholesterol and triglyceride levels. However, since a side-effect of supplementation is increased insulin resistance, niacin supplementation only provides benefits for cardiovascular health if precautions are taken.

 

[telochian]

I'm just starting down the road of understanding insulin, glucose oxidation and assorted metabolic problems, which given my recent glucose tolerance test and history of symptoms seems to be central to the fatigue/neuropathy and neurological issues I have had throughout my life.

I seem to have the opposite of insulin resistance, in my GTT, my blood was initially very low and got lower after the lemonade on steroids. Methylation starting up (accelerating?) was disastrous for me, neurotransmitters went crazy, energy was ramped up for the first couple of days and then died, neuropathy worsened, insomnia etc etc. I tried in vain to control it with a more balanced approach (Freddd's protocol) but in the end hypoglycemia, hypokalemia and potentially acidosis have forced me off it.

I'm pretty sure I'm naturally a fast acting oxidiser and from what I can tell, methylation supplements ramp up metabolic processes.......not a good combination. There is also a lot of information out there about potassium/sodium ratios and magnesium/calcium ratios and their impact on glucose oxidation and of course, methylation therapy adjusts the balance.

For whatever reason, my body doesn't oxidise, transport, absorb (into cells) glucose properly. Using methylation supplements seems to ramp up that process causing electrolyte imbalances and other metabolic disturbances which for me at least have led to hypoglycemia and acidosis as @Gondwanaland mentioned above. I think anyone with metabolic problems, diabetes, IR should be very careful with methylation therapy.

 

[Gondwanaland]

I think anyone with metabolic problems, diabetes, IR should be very careful with methylation therapy.

• Most people who start methylation supplements don't know what they are treating (like me 2 years ago).
• Most people have no clue about their glucose/insulin metabolism (like me 2 years ago) mainly because doctors never ask for fasting insulin blood test. Normal glucose levels might not mean anything.
• I am impressed with how much you know about your condition and am eager to learn more from you @telochian
• Methylation supplements can be very beneficial for a subset with insulin resistance.

hypoglycemia, hypokalemia and potentially acidosis have forced me off it.

Same for me

I'm pretty sure I'm naturally a fast acting oxidiser and from what I can tell, methylation supplements ramp up metabolic processes.......not a good combination. There is also a lot of information out there about potassium/sodium ratios and magnesium/calcium ratios and their impact on glucose oxidisation and of course, methylation therapy adjusts the balance.

Please expand on that, feel free to post some links etc

For whatever reason, my body doesn't oxidise, transport, absorb (into cells) glucose properly. Using methylation supplements seems to ramp up that process causing electrolyte imbalances and other metabolic disturbances which for me at least have led to hypoglycemia and acidosis as @Gondwanaland mentioned above. I think anyone with metabolic problems, diabetes, IR should be very careful with methylation therapy.

This is the info I am after, I need to educate myself about it, please expand on it too.

 

[telochian]

This is the info I am after, I need to educate myself about it, please expand on it too.

This explains glucose oxidation with regard to atp generation etc;
http://www.ncbi.nlm.nih.gov/books/NBK21624/

Just before posting I was reading this;

http://www.arltma.com/Articles/HypoDysDiaDoc.htm

"This type of hypoglycemia can readily be brought on by certain foods or activities that speed up the oxidation rate. Sweets, alcohol, coffee, overwork, exercise,or stress of any kind can readily trigger acute symptoms of hypoglycemia in a fast oxidizer.
Various food supplements such as vitamin C, vitamin E and B-complex may, because of their stimulatory affects on metabolism, produce the same effect."

"Fast oxidation refers to a mineral pattern of low tissue calcium and magnesium levels relative to sodium and potassium levels."

I'll post more once I've got my head around it a little better and have some further supporting evidence. From what I have read, I very much agree with the statement you made earlier about insulin sensitivity being overlooked here, but I would expand that and say that metabolic dysfunction has been overlooked.

 

[telochian]

Normal glucose levels might not mean anything

When I did my GTT; (mmol/L)

my fasting glucose was 3.6 with the "normal" limits set at 3.6 to 6
my 1 hour glucose was 3.8 with the "normal" limits set at 3.6 to 11
my 2 hour glucose was 3.6 with the "normal" limits set at 3.6 to 7.7

My insulin levels were a very normal 8.

So apparently.......I'm perfectly normal, lol. I have since bought a glood glucose meter and have been testing myself regularly throughout the day, soon after eating, 1 hour after, 2 hours after, whenever I feel weird or neuropathy worsens. This pattern has continued although I have been able to see a blood glucose spike within 30 minutes of eating carbs which is long gone by the 1 hour mark. I believe my blood sugar levels are what's called a "flat curve hypoglycemic response" (http://www.hypoglycemia.asn.au/2011/what-is-hypoglycemia/) and given that my insulin levels aren't elevated, it's likely that I have some sort of glucose oxidation/storage problem (no idea in truth, just spitballing). I can remember being as young as 7 and having the shakiness, sweating, giddiness etc of a hypoglycemic event but it isn't until now that I'm connecting the dots as to how it relates to my neuropathy, fatigue etc.

I like you had no idea of what I was treating when I started methylation therapy, I had neuropathy, fatigue, anxiety, brain fog and other neurological symptoms and a history of taking medication that blocks folate, it all seemed to fit. It seems more and more likely that it was all related to impaired glucose oxidation or storage which was worsened by metabolic stimulation from pushing my methylation system harder.

I wonder if this would all work in reverse for someone with insulin resistance. If speeding up metabolic process with methylation would drive blood sugar levels down. I am finding that my blood sugar levels are sensitive, I feel strange when I drop into the 4's (foggy, neuropathy worsens) (mmol/L) and feel strange in the high 5's (almost never seen 6). That doesn't leave much margin for error to tinker with blood sugar levels with methylation as the catalyst. I'd be very interested to hear from anyone that has experimented with testing blood sugar and methylation therapy at the same time.

At this stage, the only way forward for me seems to be ketosis and hoping that I get a good endocrinologist.

 

[Gondwanaland]

I wonder if this would all work in reverse for someone with insulin resistance.

I came up with this thread from reading the positive testimonials in low carb forums + positive testimonials from people who had success with methylation (and with ALA is the same, likewise for resistant starch). The positive testimonials (as well as the bad reactions) from these three groups (methylation, ALA/"chelation" and RS) are just too similar. So I interpret that people with insulin resistance are far more likely to have success with any of these treatments.

I'd be very interested to hear from anyone that has experimented with testing blood sugar and methylation therapy at the same time.

I think that blood glucose can generally be of little meaning, we need insulin levels. Except made for what you just reported, which I am still processing.

the only way forward for me seems to be ketosis

To me it seems that no matter what you eat, your body's response is as if you were always in ketosis
Ketosis for me is the evil! I just can't handle the hypoglycemia and the acidosis. I am done with low carb. I am eating all the fruit, rice, beans and potatoes my lectin sensitivity allows me And avoid any supplement that is supposed to improve insulin sensitivity such as Taurine, vit A, acidophilus, ALA, Mfolate etc

 

[Gondwanaland]

(http://www.hypoglycemia.asn.au/2011/what-is-hypoglycemia/)

Hypoglycemia is a stress symptom. This causes potassium to be excreted in the urine and salt to be retained, contributing to hypertension. Adelle Davis suggests that the unpleasant feelings of hypoglycemia may be relieved by taking potassium chloride tablets.

Very interesting reading, thanks for the link.

 

[telochian]

I started posting on a prominent diabetes, hypoglycemia forum today and someone pointed me to this;

Very interesting indeed.

 

[Violeta]

Berberine HCl is good for insulin resistance. Maybe that's because it's good for fatty liver. I don't have time to get the links right now, but there are a lot of them.

Liver involved in methylation. Read at Chris Masterjohn's Daily Lipid blog with respect to NAFLD.

 

[ahmo]

Berberine is also hard on the liver, generally suggested to cycle it.

 

[picante]

Wow, Izzy, your hypothesis is soooo intriguing! I haven't had time/energy yet to delve into the links. Have you thought about doing a poll? Or maybe an informal thread asking people to report their experience with methylation + their insulin status?

What do you think: If I get frequent hypoglycemia, would that necessarily mean that I'm not insulin resistant? And would the people who are "insulin sensitive" (don't know the proper term) tend to have low BMI (body mass index)?

 

[Gondwanaland]

Wow, Izzy, your hypothesis is soooo intriguing! I haven't had time/energy yet to delve into the links. Have you thought about doing a poll? Or maybe an informal thread asking people to report their experience with methylation + their insulin status?

I might start a thread asking how many people have ever had their fasting insulin measured
You gotta watch the interview @telochian posted

What do you think: If I get frequent hypoglycemia, would that necessarily mean that I'm not insulin resistant?

That is what I have been trying to figure out Hope you can help me

 

[Gondwanaland]

people who are "insulin sensitive" (don't know the proper term) tend to have low BMI (body mass index)?

Being thin does NOT always mean that one is insulin senstitive. I think the number is 40% of people who have insulin resistance are NOT overweight.

 

[Gondwanaland]

Liver involved in methylation. Read at Chris Masterjohn's Daily Lipid blog with respect to NAFLD.

My NAFLD healed just by going gluten free. However, homocysteine didn't improve on its own because I couldn't increase serum B12 levels with the low choline diet I was eating back then.

 

[Gondwanaland]

These sites summarize some of the research about the role of some B vits and AAs in insulin/glucose metabolism:

http://www.progressivehealth.com/vitamins-that-help-reduce-high-blood-sugar.htm
7 Vitamins That Help Control Blood Sugar
1 B Vitamins
2 Vitamin B1
3 Vitamin B3
4 Vitamin B6
5 Vitamin B12
6 Vitamin C
7 Vitamin D
8 Vitamin E

https://examine.com/stacks/improving-insulin-sensitivity/
Improving Insulin Sensitivity
Suggested Supplements
L-Carnitine
Resveratrol
Fenugreek
Tauroursodeoxycholic Acid
Green Tea Catechins
Berberine

http://hyper.ahajournals.org/content/55/6/e26.full
Oral Acetyl-L-Carnitine Therapy and Insulin Resistance

 

[Gondwanaland]

I started posting on a prominent diabetes, hypoglycemia forum today and someone pointed me to this;

Very interesting indeed.

This is the most important medical information I have ever seen.

 

[telochian]

This is the most important medical information I have ever seen.

Yeah it really does contain some profound information, ticks many boxes for me. I have, in the past been diagnosed with menieres disease (even though I'm sure I was misdiagnosed) and when they mentioned the blood sugar connection, I was stunned. I'll be pushing my doctor for a Kraft style 5 hour insulin test to determine my insulin status, even though my fasting insulin on the GTT was perfectly normal.

In terms of hypoglycemia, it really depends on what the root cause of it is. From my understanding, people in the early stages of diabetes can experience hypoglycemia due to "hyperinsulinemia" which is a situation where your pancreas is churning out way too much insulin in reference to blood sugar levels and is in the early stages of "burning out" the beta cells. Once burnt out, then the pancreas no longer produces insulin and then the symptoms of "diabetes" as most doctors would diagnose (high blood sugar etc) begins. But again, there are many and varied reasons for having low blood sugar, if your insulin tests are normal, then it's probably something much rarer, genetic or insulinoma or something.

http://www.agsdus.org/html/glycogenandgsds.html

This is part of what Dr Kraft is saying in the aforementioned video, high blood sugar is one of the final symptoms of diabetes, by the time this happens, much of the damage to internal organs, heart etc is already done. Anyone with blood sugar problems, high or low, should look at having their insulin tested multiple times within a 2-5 hour test.

 

[picante]

I still haven't had time to explore the links & videos here, but need a place to put this information. I keep running across this kind of thing when I'm looking for something else:

These two quotes are from an article on treating the metabolic causes of diabetic neuropathy, found here: -http://www.podiatrytoday.com/blogged/why-you-should-consider-use-supplements-management-diabetic-neuropathy#sthash.v6v7XbvI.dpuf

Inositol is a methyl donor.

Inositol plays a role in electrolyte flux across neural membranes. It may be deficient in patients with diabetic neuropathy. Supplementation with 500 mg tid-qid has been helpful in the treatment of neuropathy.54 -

ALA is something I didn't tolerate for long when I tried it for chelation.

Alpha lipoic acid is an antioxidant. Researchers have shown that the use of alpha lipoic acid in insulin-resistant patients is associated with reduced body mass index, waist circumference and total cholesterol as well as improved insulin sensitivity, and suggested it as an adjunctive therapy for the treatment of patients with type 2 diabetes.27

Symptoms/risks associated with inositol deficiency, from http://www.acu-cell.com/bx2.html

Inositol: peripheral neuropathy, panic-anxiety attacks, agoraphobia, bulimia, unipolar & bipolar depression, obsessive-compulsive disorder (up to 18g daily), polycystic ovary syndrome (PCOS), insulin resistance.