No study existed that could honestly be seen as testing the HCV-carbohydrate hypothesis at any level. Or so I thought; but thanks to informants Silvia and Samir, I received this 2011 paper yesterday
Microbiol Immunol. 2011 Nov;55(11):774-82. doi: 10.1111/j.1348-0421.2011.00382.x.
Now there is a common objection to any method of inhibiting viral replication, that viral load does not always correlate with liver damage in Hepatitis C (though it does influence the response to treatment). There are three main reasons why this is so;
|The mysterious "Compound C", an AMPK inhibitor|
The mysterious “Compound C” which inhibits AMPK is interesting too. AMPK is basically controlling your cell’s metabolic rate. At higher glucose levels, more AMPK = less HCV replication. But at the lowest glucose level, where HCV replication is inhibited, lowering AMPK with Compound C inhibits replication even further. rT3 anyone?
Anyway, there is no point having low fasting blood glucose if you are not usually fasting, so any attempt to exploit this effect by a low-carb diet (and I don’t rule out other types of diet also being able to keep fasting BG around 1 g/L or 5.5mM for some people, but VLCKDs do seem the obvious choice) should probably be in an intermittent fasting context like 16:8. Also, the point might not be to obsessively measure blood glucose and keep it at 4mM, but simply, if it’s high, try to get it a bit lower; within the normal range of 4-7mM being better than above it. 4.5 g/L was chosen in the study as an abnormally high blood glucose level, one associated with type 2 diabetes, a disease associated with chronic HCV infection.
(note: I appreciate that in the US, Egypt, and some other countries BG is measured in mg/dL, which is 100x the g/L measurement, and that there is probably a great deal to be said about what range is ideal, so I have just stuck to received opinions and kept the scienticians' g/L counts, as I am a novice to the business of measuring BG. The only fasting BG test I could could find of my own was 6mM, on a moderately low carb diet (100-150g); it isn't something my doctors usually order.)
The Kinks found that low-carb diets were perfectly effective for weightloss in 1970
(Update 1 - in HCV Gt2-infected Huh 7.5 cells, glycolysis is upregulated, as is lipogenesis and gluconeogenesis, while glucose uptake is down regulated. "Although infected cells may be attempting to counter the HCV-induced low cellular glucose levels by increasing gluconeogenesis, they appear to be unable to counteract both increased glycolysis as well as decreased glucose transport". This might be what makes HCV assembly especially vulnerable to low ambient glucose levels.
Update 2 - Many of the lipid metabolism genes upregulated in this study are targets of the PPARα transcription factor (40). One of these genes, the TXNIP gene, which functions as a negative feedback inhibitor of PPARα (33), was shown to be essential for HCV replication and secretion by siRNA silencing. A recent study demonstrating that agonists of PPARα suppress the replication of HCV indicated that the inhibition of PPARα by TXNIP may be important for HCV infection (32). Increased expression of TXNIP also occurs when intracellular glucose levels are high (14). A recent siRNA screen for host factors involved in JFH-1 HCV replication demonstrated that silencing MXLIPL, a glucose-responsive transcription factor that induces TXNIP expression, also significantly reduced JFH-1 replication.
In addition, hepatic overexpression of a Txnip transgene in wild-type mice resulted in elevated serum glucose levels and decreased ketone levels.)
The Credit-where-it's-due department thanks Carbsane for posting about this paper, which indicates that HbA1c may not be a reliable measurement of long-term glucose levels in people with chronic Hep C, who may have deficient or short-lived hemoglobin, and therfore artificially low HbA1c levels for this reason.
"In the present study, participants with low HbA1c values had unfavorable profiles of red blood cell related factors, iron storage, and liver function."