Thank you but I don't understand why it can be worse...Do you?
No, I sure don't. I'm not too knowledgeable in these things. I'm sure you know more than me.
The only thing I know is that, per Rich, when the methlylation cycle is dysfunctional it causes a whole host of problems and cascades of events and problems converting, etc. Rich would give the details as to what would happen but I don't have a memory for details. Definitely when glutathione is depleted oxidative stress is created.
All I know is what Rich says...:
Hi, Sasha and the group.
It is known that the unsaturated (essential) fatty acids are the most vulnerable molecules in the cells to oxidative damage.
One is that so long as the state of oxidative stress is present, there will continue to be damage to the unsaturated fatty acids. Furthermore, the formation of lipid peroxides from these fatty acids is a chain reaction process, which feeds on itself. Therefore, while it should be beneficial to supplement these fatty acids, there needs to be a parallel effort to stop the oxidative stress. Otherwise, the situation might actually become worse from the supplementation.
...and this study:
Metab Syndr Relat Disord. 2011 Oct;9(5):397-401. doi: 10.1089/met.2010.0140. Epub 2011 May 11.
Oxidative stress is activated by free fatty acids in cultured human hepatocytes.
Soardo G1, Donnini D, Domenis L, Catena C, De Silvestri D, Cappello D, Dibenedetto A, Carnelutti A, Bonasia V, Pagano C, Sechi LA.
Author information
Abstract
- 1Liver and Hypertension Unit, Department of Pathology and Experimental and Clinical Medicine, University of Udine, Udine, Italy. soardo.giorgio.@aoud.sanita.fvg.it
BACKGROUND:
Nonalcoholic fatty liver disease (NAFLD) is strongly associated to oxidative stress, metabolic syndrome, and cardiovascular risk. Hepatocytes overloaded with fatty acids (FA) could generate substances that interfere with endothelial function, providing a potential explanation for this association. We have investigated the response of cultured human hepatoblastoma cells (Hep-G2) that were exposed to FA by measuring markers of oxidative stress and thrombosis and expression of the insulin receptor.
METHODS:
Hep-G2 cells were conditioned with a mixture of FA with or without N-acetyl-L-cysteine (NAC), glutathione (GSH), or adiponectin (ADN). After 7 days, we measured intracellular GSH (iGSH), nitric oxide (NO), malondialdehyde (MDA), and tissue plasminogen inhibitor-1 (PAI-1). Real-time polymerase chain reaction (PCR) was used to determine gene expression of inducible nitric oxide synthase (iNOS) and insulin receptor (INS-R).
RESULTS:
Exposure to FA decreased iGSH and NO levels in Hep-G2 cells and increased MDA and PAI-1 production. Gene expression of iNOS and INS-R in Hep-G2 cells was decreased by exposure to FA. Co-incubation with NAC and GSH prevented the change of iNOS mRNA levels, but not of INS-R; co-incubation with ADN restored the gene expression of INS-R, but not of i-NOS. ADN prevented also the FA-induced increase in MDA in cultured human endothelial cells.
CONCLUSION:
Exposure to FA activates oxidative stress and production of prothrombotic markers and decreases expression of insulin receptors in cultured human hepatocytes. These effects of FA are partially prevented by ADN and might contribute to the increased cardiovascular risk in patients with NAFLD and metabolic syndrome
http://www.ncbi.nlm.nih.gov/pubmed/21561340
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