How Oxaloacetate CFS may Help with ME/CFS

A statistically significant shortage of the energy metabolite “oxaloacetate” has been documented in ME/CFS patients clinically. This shortage of oxaloacetate can affect metabolism in many ways.

A. ME/CFS patients chronically activate the NF-kB inflammation pathway. Providing supplemental oxaloacetate decreases the activity of the NF-kB pathway, reducing the cytokine storm.

Oxaloacetate Supplementation decreases the NF-kB Inflammation Pathway

Wilkins HM, Harris JL, Carl SM, et al. Oxaloacetate activates brain mitochondrial biogenesis, enhances the insulin pathway, reduces inflammation and stimulates neurogenesis. Hum Mol Genet. 2014;23(24):6528-6541. doi:10.1093/hmg/ddu371 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4271074/

B. Althernative energy production via fermentation in the cytoplasm has been identified in ME/CFS patients clinically. Oxaloacetate reduces glycolysis and the Warburg Effect, reducing cytosolic lactate production, normalizing cellular energy production.

Omkar Ijare, David Conway, Alan Cash, David Baskin, Kumar Pichumani, CBMT-49. OXALOACETATE ALTERS GLUCOSE METABOLISM IN GLIOBLASTOMA: 13C ISOTOPOMER STUDY, Neuro-Oncology, Volume 21, Issue Supplement_6, November 2019, Pages vi43–vi44, https://doi.org/10.1093/neuonc/noz175.171

https://academic.oup.com/neuro-oncology/article-abstract/21/Supplement_6/vi43/5620031?redirectedFrom=fulltext

C. ME/CFS patients have a lower NAD+/NADH ratio. Oxaloacetate increases the NAD+/NADH ratio.

Wilkins HM, Harris JL, Carl SM, et al. Oxaloacetate activates brain mitochondrial biogenesis, enhances the insulin pathway, reduces inflammation and stimulates neurogenesis. Hum Mol Genet. 2014;23(24):6528-6541. doi:10.1093/hmg/ddu371

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4271074/

D. The mitochondria, powerplants of the cell, malfunction in ME/CFS patients. Oxaloacetate activates new mitochondrial biogenesis via an increase in PGC1-alpha.

Oxaloacetate activates new mitochondrial biogenesis via an increase in PGC1-alpha

Wilkins HM, Harris JL, Carl SM, et al. Oxaloacetate activates brain mitochondrial biogenesis, enhances the insulin pathway, reduces inflammation and stimulates neurogenesis. 

Hum Mol Genet. 2014;23(24):6528-6541. doi:10.1093/hmg/ddu371

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4271074/

E. ME/CFS patients have a lower activation of AMPK, and reduced glucose uptake. Oxaloacetate activates AMPK and increases glucose uptake in clinical trials.

Oxaloacetate lowers fasting glucose levels by increases cellular glucose uptake

Yoshikawa K. Studies on the anti-diabetic effect of sodium oxaloacetate. Tohoku J Exp Med. 1968 Oct;96(2):127-41. doi: 10.1620/tjem.96.127. PMID: 4884771. https://pubmed.ncbi.nlm.nih.gov/4884771/