term ketogenic dieting although fasting has been studied to some degree. Early ketogenic diet
literature mentions a condition called ‘alloxan’ or ‘starvation diabetes’, referring to an initial
insulin resistance when carbohydrates are reintroduced to the diet following carbohydrate
restriction (2).
In brief, the initial physiological response to carbohydrate refeeding looks similar to what is
seen in Type II diabetics, namely blood sugar swings and hyperinsulinemia. This type of
response is also seen in individuals on a CKD. It should be noted that this response did not occur
universally in research, being more prevalent in those who had preexisting glucose control
problems. As well, exercise appears to affect how well or poorly the body handles carbohydrates
during refeeding.
One hypothesis for this effect was that ketones themselves interfered with insulin binding
and glucose utilization but this was shown not to be the case (3,4). In fact, ketones may actually
improve insulin binding (2). The exact reason for this ‘insulin resistance’ was not determined until
much later. The change was ultimately found to be caused by changes in enzyme levels,
especially in those enzymes involved in both fat and carbohydrate burning (5). High levels of free
fatty acid levels also affect glucose transport and utilization (6).
Long periods of time without carbohydrate consumption leads to a down regulation in the
enzymes responsible for carbohydrate burning. Additionally, high levels of free fatty acids in the
bloodstream may impair glucose transport (6).
This change occurs both in the liver (5) and in the muscle (5,7). During carbohydrate
refeeding, the body upregulates levels of these enzymes but there is a delay during which the body
may have difficulty storing and utilizing dietary carbohydrates. This delay is approximately 5
hours to upregulate liver enzyme levels and anywhere from 24-48 hours in muscle tissue (8,9).
While there is a decrease in carbohydrate oxidation in the muscle, this is accompanied by an
increase in glycogen storage (7).
These time courses for enzyme up-regulation correspond well with what is often seen in
individuals on a CKD, which is really nothing more than a ketogenic diet followed by carbohydrate
refeeding done on a weekly basis. Frequently, individuals will report the presence of urinary
ketones during the first few hours of their carb-loading period, seeming to contradict the idea that
carbohydrates always interrupt ketosis. This suggests that the liver is continuing to oxidize fat
at an accelerated rate and that ingested carbohydrates are essentially not being ‘recognized’ by
the liver.
After approximately 5 hours, when liver enzymes upregulate, urinary ketone levels
typically decrease as liver glycogen begins to refill. Another interesting aspect of carbohydrate
refeeding is that liver glycogen is not initially refilled by incoming glucose. Rather glucose is
released into the bloodstream for muscle glycogen resynthesis (especially if muscle glycogen
stores are depleted) initially, refilling liver glycogen later.
In practice, many individuals report what appears to be rebound hypoglycemia (low blood
sugar) either during the carb-up or during the first few days of eating carbohydrates when
ketogenic eating is ended, for the reasons discussed above.
Ketones themselves do not appear to alter how cells respond to insulin (4) which goes
against the popular belief that ketogenic diets somehow alter fat cells, making them more likely
to store fat when the ketogenic diet is ended. Practical experience shows this to be true, as many