I've been practicing a relatively low-carb diet for over a year. Based on extensive research, I was reasonably sure that this was not only good for long-term health, but also better than higher-carb diets because of reductions in glucose and insulin.
So when I first saw the 2009 study below, my first reaction was, "NO WAY! This contradicts all my other research!"
Believing that the study must be flawed somehow -- or perhaps applied only to diseased animals -- I read the full text to try to negate its relevancy to healthy, lean humans. However, I was unable to do so. Maybe I lack the expertise, but this study makes things look bad for low-carb diets.
Below are some selected excerpts from this 2009 study, which is entitled "Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans".
...in skeletal muscle of both rodents and humans [even lean, healthy humans], a diet high in fat increases the H2O2-emitting potential of mitochondria, shifts the cellular redox environment to a more oxidized state, and decreases the redox-buffering capacity...
[My comment: H2O2 is hydrogen peroxide, which Wikipedia states is one of the most powerful oxidizers known.]
...
The response to carbohydrate ingestion, however, is likely transient, owing to the rapid clearance of glucose. By contrast, a diet high in fat generated a persistent reduction in GSH/GSSG [the ratio of reduced glutathione to oxidized glutathione] (i.e., evident even after 12-hour fast), suggesting that the clearance and metabolism of dietary lipids may elicit a more sustained elevation in H2O2 emission, shifting the cellular redox environment to a more persistent oxidized state."
...
[In rats on a normal diet (NOT high-fat)] glucose ingestion elicited an approximately 2-fold increase in GSSG [oxidized glutathione] and an approximately 50% reduction in the GSH/GSSG ratio presumably reflecting an increase in mitochondrial H2O2 emission in response to the insulin-stimulated increase in glucose uptake and oxidation..."
[My comment: in other words, the study shows that high serum glucose and high-fat diets both seem to damage insulin sensitivity by the same mechanism, which seems likely to create cumulative damage that may ultimately result in diabetes and other diseases.]
...
Total cellular glutathione content (GSHT) decreased by approximately 30% in high-fat diet-fed rats ...suggesting that high fat intake compromises total GSH-mediated redox buffering capacity in skeletal muscle.
...
[In lean, insulin-sensitive male humans] ...4 hours after consumption of a high-fat meal (35% of daily energy expenditure; 60%–65% fat), and after 5 days of consumption of a similar high-fat diet ...maximal mitochondrial H2O2 emission was increased by more than 2-fold ...Moreover, this heightened mitochondrial H2O2-emitting potential persisted through the 5-day high-fat diet regimen. Cellular GSH/GSSG ratio decreased by approximately 50% within 4 hours after consumption of the high-fat meal and remained at this level through the 5-day high-fat diet ...again indicative of a shift in redox environment to a more oxidized state.
...
Bonnard et al. (13) recently reported that deteriorations in mitochondrial structure and function in skeletal muscle of mice appear only after several months of high-fat feeding, well after insulin resistance has developed. The implication is that mitochondrial dysfunction, similar to insulin resistance, is a consequence rather than a primary cause of the altered cellular metabolism...
...
Koves et al. (36) have recently reported the presence of ketone bodies and the accumulation of partially oxidized fatty acids in skeletal muscle of rats fed a high-fat diet, implying that an oversupply of lipids overwhelms the beta-oxidation and TCA cycle pathways, generating metabolic intermediates that otherwise are not present. The generation of surplus reducing equivalents would in turn be expected to elevate the redox state of complex I and/or the ubiquinone pool ...even a small surplus of reducing equivalents would be predicted to elicit an exponential increase in the rate of superoxide production and H2O2 emission from mitochondria...
The full text of the study is at http://www.pubmedcen...i?artid=2648700
There's also the following study that shows negative effects when fat comprises as little as 50% of calories (rather than 60% like the study above); but this study seems lower quality: http://diabetes.diab.../1926.full.html
Also the following quote from Aubrey de Grey & Michael Rae seems relevant:
...the metabolic state that [low-carb] diets induce (the notorious “ketosis”) has the unfortunate side effect of causing a jump in the production of the oxoaldehyde methylglycoxal, a major precursor of AGE’s that is also, ironically, produced within the cells of diabetic patients when they are forced to take in more glucose than they can immediately process. A recent study tested the size of this effect in healthy people who successfully followed the first two phases of the Atkins diet for a month, and who had the ketones in their urine to prove that they were sticking to the diet. These previously healthy people suffered a doubling of their methylglycoxal levels, leading to concentrations even worse than those seen in poorly controlled diabetics. Like other oxoaldehydes, methylglycoxal is far more chemically reactive than blood sugar (up to 40,000 times more reactive, in fact), and is known to cause wide-ranging damage in the body, of which AGE cross-links are but one example. This potentially makes the Atkins diet a recipe for accelerated AGEing, not a reprieve from it.
Finally, perhaps someone will spot reasons why these findings don't fully apply to how low-carb diets are actually practiced. If not, the idea that low-carb diets are healthy for long-term use seems to have been dealt a major blow.
(Edit: Fixed "quote" tags.)
Edited by kodi, 01 August 2009 - 02:46 AM.