Here us a new study that looks a bit more deeply at the whole area. Much of it is beyond me, but there is some interesting stuff there.
Emerging evidence indicates that impaired cellular energy metabolism is the defining characteristic of nearly all cancers regardless of cellular or tissue origin. In contrast to normal cells, which derive most of their usable energy from oxidative phosphorylation, most cancer cells become heavily dependent on substrate level phosphorylation to meet energy demands. Evidence is reviewed supporting a general hypothesis that genomic instability and essentially all hallmarks of cancer, including aerobic glycolysis (Warburg effect), can be linked to impaired mitochondrial function and energy metabolism. A view of cancer as primarily a metabolic disease will impact approaches to cancer management and prevention.The whole paper is available as pdf
2 comments:
"Impaired mitochondrial function" makes me think of impaired CoQ10 pathways and statins. Hmm..
http://health.ucsd.edu/news/2009/1-29-statin-study.htm
http://www.ncbi.nlm.nih.gov/pubmed/15843897
This seems to fit in pretty well with that paper... except for the part about ROS being bad.
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The antioxidant alpha-lipoic acid (ALA) has been shown to affect a variety of biological processes associated with oxidative stress including cancer. We determined in HT-29 human colon cancer cells whether ALA is able to affect apoptosis, as an important parameter disregulated in tumour development. Exposure of cells to ALA or its reduced form dihydrolipoic acid (DHLA) for 24 h dose dependently increased caspase-3-like activity and was associated with DNA-fragmentation. DHLA but not ALA was able to scavenge cytosolic O2-* in HT-29 cells whereas both compounds increased O2-*-generation inside mitochondria. Increased mitochondrial O2-*-production was preceded by an increased influx of lactate or pyruvate into mitochondria and resulted in the down-regulation of the anti-apoptotic protein bcl-X(L). Mitochondrial O2-*-generation and apoptosis induced by ALA and DHLA could be prevented by the O2-*-scavenger benzoquinone. Moreover, when the lactate/pyruvate transporter was inhibited by 5-nitro-2-(3-phenylpropylamino) benzoate, ALA- and DHLA-induced mitochondrial ROS-production and apoptosis were blocked. In contrast to HT-29 cells, no apoptosis was observed in non-transformed human colonocytes in response to ALA or DHLA addition. In conclusion, our study provides evidence that ALA and DHLA can effectively induce apoptosis in human colon cancer cells by a prooxidant mechanism that is initiated by an increased uptake of oxidizable substrates into mitochondria.
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So, part of the insulin-mimetic activity of alpha lipoic acid may be that it encourages mitochondrial respiration. They did some worm studies where they blocked glucose metabolism, and ROS and lifespan both increased, vitamin c, vitamin e and N acetyl cysteine all blocked both effects. Maybe they should have tried lipoic acid? They have done studies where lipoic acid increased rodent lifespan. I'm not aware of any studies where those other three did any such thing.
Increased mitochondrial uptake of lactic acid? Remember those genetically altered supermice, they ate 60 percent more, had much greater endurance, and they built up less lactic acid when they exercised? I think they were also more aggresive than normal mice. (Maybe normal mice just have social anxiety disorder?) And even though they ate more, they lived longer? I'm pretty sure you posted about them a few years ago.
I stopped taking alpha lipoic acid a few years ago, I figured, why do I need help with blood sugar, since I eat low carb. Then I read Bernstein-- he reduced his personal insulin requirements by a third when he added lipoic acid.
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