Metformin - Another totally random, off-the-wall question

[JaneTX]

If anyone also takes Metformin here, does it help your MC symptoms, make it worse, or no observable change?

This past week I've been reading stuff over in the Lupus camp and ran across some fascinating new research into increased glucose metabolism by activated lymphocytes. In labs, it's been noticed that Metformin may normalize lymphocyte behavior, which in theory may calm down Microscopic Lymphocyte Colitis, though Metformin is known to cause diarrhea and intestinal upset which is contradictory. So in theory it also leads to the question whether MC may be a symptom of insulin resistance.

Resting lymphocytes do not consume much energy, but activated lymphocytes start consuming a lot of glucose to generate those antibodies and cytokines and to multiply, so restricting their access to energy sources is an interesting angle for potentially controlling autoimmune diseases.

[Gabes-Apg]

So in theory it also leads to the question whether MC may be a symptom of insulin resistance.

or it can go the other way - is insulin resistance a symptom of MC??

insulin moderation in the body involves multiple organs, multiple nutrients. one of these is Magnesium
ongoing inflammation and nutrient deficiencies in the body leads to multiple symptoms/conditions.

reduce inflammation and fix nutrient imbalance and you can clear/resolve lots of health issues

[tex]

To support Gabes' point, from my book, 8 Ways to Prevent Pancreatic Cancer, pages 25–26:

But this leads us to the magnesium connection again.
As mentioned in the previous chapter, magnesium deficiency plays an important role in the development of insulin resistance and type 2 diabetes. Researchers have shown that both hypertension and type 2 diabetes involve low intracellular magnesium levels (Takaya, Higashino, & Kobayashi, 2004).26 In the research article cited, Takaya, Higashino, and Kobayashi (2004) concluded that because magnesium is necessary for the proper utilization of glucose, and it's also used for insulin signaling, an intracellular magnesium deficiency may alter glucose availability and contribute to the development of insulin resistance.

Magnesium and insulin are co-dependent.
One cannot function properly without the other. And this is a 2-way street in many regards. Not only does a magnesium deficiency cause insulin resistance in the cells of the body, and reduced insulin production by the pancreas, but there is a reciprocal effect. Insulin is responsible for the transport of nutrients to locations where they can either be immediately utilized or stored for future use. When the availability and effectiveness of insulin is compromised, extra magnesium in the blood cannot be properly stored, so most of it may be wasted, instead (Sircus, 2009).27

This can dramatically increase the odds that diabetes patients may develop a magnesium deficiency. And of course as the magnesium deficiency becomes worse, insulin resistance may increase and insulin production by the pancreas may decline even further.

But even stronger evidence of the association between magnesium deficiency and diabetes has been found by researchers. Research published by Hruby et al. (2014) found that higher magnesium intake reduces the risk of insulin resistance and the risk of progression from a prediabetic condition to diabetes.28 In that study, people who had the highest magnesium intake had only about half the risk (53 %) of metabolic interference or diabetes development compared with those who had the lowest magnesium intake. This information is especially important for those who have been told by their physicians that their blood test results indicate that they are at a stage known as prediabetes.

References 26–28 from that quote:

26. Takaya, J., Higashino, H., & Kobayashi, Y. (2004). Intracellular magnesium and insulin resistance. Magnesium Research, 17(2), 126-136. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/15319146

27. Sircus, M. (2009, December 8). The Insulin Magnesium Story [Web log message]. Retrieved from http://drsircus.com/medicine/magnesium/ ... um-story-2

28. Hruby, A., Meigs, J. B., O’Donnell, C. J., Jacques, P. F., & McKeown, N. M. (2014). Higher Magnesium Intake Reduces Risk of Impaired Glucose and Insulin Metabolism and Progression From Prediabetes to Diabetes in Middle-Aged Americans. Diabetes Care, 37(2), 419-427. Retrieved from http://care.diabetesjournals.org/content/37/2/419

Tex

[JaneTX]

Unfortunately hefty magnesium and nutrient supplementation never budged the needle on my daughter's autoimmune problems (including MC).

For awhile now I've been concerned that underperforming FOXP3 and IL10 genes (and my daughter has an IL10 gene that really stinks, and a suspect SNP in her STAT3 gene) cause an imbalance among Th1, Th2, Th17 and Treg lymphocytes, weighted against Tregs. Just as there seems to be an interrelationship between Th1 and Th2, so too between Th17 and Tregs, particularly in the digestive tract. A deficiency of Tregs seem to promote autoimmune disorders by not being able to keep the attack arm of the immune system in check. So I've been looking at how one could go about promoting Tregs to compensate for a genetic predisposition against adequate Treg production. Then I ran across this article which got me thinking about insulin resistance and Metformin, hence my query here.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4567351/
Metformin Ameliorates Inflammatory Bowel Disease by Suppression of the STAT3 Signaling Pathway and Regulation of the between Th17/Treg Balance
2015
"Treatment with metformin inhibited the expression of interleukin (IL)-17, p-STAT3, and p-mTOR. In contrast, metformin treatment increased expression levels of p-AMPK and Foxp3. In addition, expression of inflammatory cytokines decreased in a dose-dependent manner in inflamed human HT-29 cells cultured with metformin at various concentrations."

[tex]

Tregs have long been claimed to be a cause of autoimmune disorders (despite the fact that so-called autoimmune disorders are always triggered by some exogenous allergen). The problem with using medications to treat this problem is that doing so not only does not address the cause, but there is no such thing as a medication without side effects. This is such a universal problem that many meds are prescribed for off-label use because of some side effect. But of course they usually come with additional side effects that cause problems, so I would be very surprised if you can find a med that will enhance Treg production without causing unacceptable side effects (additional adverse issues). Whether one is treating lymphocyte production/development, enzyme production, or whatever, a deficiency of some nutrient, mineral, or vitamin, or a reaction due to an exogenous antigen, is almost always responsible for perpetuating the problem, even though it may not have been the initial or even the primary cause.

Proponents of the use of medications choose to ignore the cause (which means that it may continue to be a trigger) and treat the problem by trying to overwhelm it with one or more powerful drugs, which of course often leads to other problems because of the cumulative side effects of that/those drug/s.

I'm not advising you to eschew the use of drugs — and I'm not pretending to know the answer. I'm just suggesting that you step back and reassess the situation, and give some serious thought to the basic issues. Who knows — it might lead to an "Aha" moment.

Tex