Fibromyalgia (FM) – Mitochondrial Dysfunction Helped by Metformin and Weight Loss

Adenosine Monophosphate activated Protein Kinase (AMPK) regulates cell metabolism  i.e “AMPK has a central regulatory role in cell metabolism, mitochondrial biogenesis and oxidative stress response”. Recent study of FM fibroblasts found AMPK downregulated.”AMPK down-regulation [is] at least in part responsible for the impaired oxidative stress response and mitochondrial dysfunction observed in Fibromyalgia”. AMPK activation can be obtained by metformin.  Also perhaps by weight loss as serum from weight loss restricted mice activates it. Implications are that weight loss and metformin can set one’s metabolism some straight. FM subjects are susceptible to oxidative stress potentially leading to cell deaths and above measures help contain that as well.

Biochim Biophys Acta. Molecular Basis of Disease. 2015 Jul;1852(7):1257-67.
doi: 10.1016/j.bbadis.2015.03.005.
Metformin and caloric restriction induce an AMPK-dependent restoration of
mitochondrial dysfunction in fibroblasts from Fibromyalgia patients.
Alcocer-Gómez E(1), Garrido-Maraver J(2), Bullón P(3), Marín-Aguilar F(4), Cotán
D(2), Carrión AM(5), Alvarez-Suarez JM(6), Giampieri F(7), Sánchez-Alcazar JA(2),
Battino M(8), Cordero MD(9).
http://www.ncbi.nlm.nih.gov/pubmed/25779083

• Fibroblasts – cells usually used to make tissue
• Mitochondria – energy furnaces in cell determining cell vitality and health
• AMPK is a marker of tissue metabolism
• FM patients were compared with controls – their fibroblasts put in cultures externally
• “AMPK was not phosphorylated in fibroblasts from FM patients and was associated with decreased mitochondrial biogenesis, reduced oxygen consumption, decreased antioxidant enzymes expression levels and mitochondrial dysfunction.”
• Metformin, introduced in tissue culture had beneficial effects

Example of poor enzymatic function in mitochondria in FM:

Cell oxidation (sickness) seen more commonly in FM fibroblasts:

Without control of free radicals, cells in FM are more susceptible to sickness and death- example of sensitivity to peroxide (H2O2) leading to cell death versus controls  – seen below as increased risk but benefits from  metformin:

Comment – implications are that weight loss and metformin could be beneficial in FM. What was not done, is metformin given to FM subjects to see what effects their could be. Mitochondrial disease has been implicated in FM for some time. There is good evidence that mitochondrial disease is related to depression (certain depressions inherited from mother as mother passes mitochondria to offspring) – Bipolar particularly – and there is evidence that 1/4 FM subjects are bipolar:
Wilke, William S., Carmen E. Gota, and David J. Muzina.
Fibromyalgia and bipolar disorder: a potential problem?.
Bipolar disorders 12.5 (2010): 514-520.
http://www.ncbi.nlm.nih.gov/pubmed/20712752

This heightens need to treat any depression seriously but also consider FM a metabolic disease. Metformin is an interesting agent as it is shown to help prevent and slow down  certain cancers and would not be bad to take. FM is becoming more legit!

Practical case – 25 year old with bipolar and fibromyalgia. Obese and told could not have hip labral tear surgery unless lost weight. I put her on metformin 1 gm twice daily because it sometimes helps people lose weight. She noticed her pains dropped by 2/10 points but thought maybe it was due to the fact she was losing weight – it might have been both the weight loss and metformin. She also noted her bipolar disease improved and she had less hypomanic attacks. I am convinced that those with fibromyalgia and hereditary depression are quite likely to benefit from metformin and another metabolic stimulator – B12 which when given to people with more neurogenic chronic pain can drop pain 20% as well – but works best, at least initially, 1000 ug subcut daily for 2 weeks