I've always been interested in the biochemical effects of the zone diet and its functionality as a de-facto calorie restriction (CR) diet. If you total up caloric intake from what's recommended by the zone calculator in terms of protein, carbohydrate, and fat blocks, the result is remarkably low. Normal people are recommended to eat in a range typically considered to be CR. As many of you may know CR diets in animals as closely related to humans as rhesus monkeys have been associated with increased longevity and reduced incidence of chronic disease with age.
There is a community of CR practitioners independent of any zone affiliation. Many of these people, in addition to reducing overall caloric intake, also reduce protein intake in an attempt to reduce levels of the protein insulin-like growth factor (IGF-1). They see this as desirable because reduced levels have been associated with increased longevity in humans and animals.
However, apparently now many members of the community doing this have developed impaired glucose tolerance, a sign of pre-diabetes. Certain people have also complained of ills such as low libido, low testosterone, and reduced bone density.
Since zone is already regarded as "high-protein" in spite of the fact that protein only constitutes 40% of total calories, my guess is that these people are consuming truly low levels of protein in their diets, much lower than would be recommended under zone philosophy.
I was wondering if any more science oriented zoners out there might hazard a zone-inspired biochemical explanation of why certain low-protein consuming CR practitioners are experiencing these problems. What happens from a chronic inflammation and hormonal standpoint when people stick to a diet, for many years and with zealous discipline, which is comparably low calorie to the zone but much lower in protein? Also I assume that most of these people are aware of the concept of glycemic index and tailor their carbohydrate consumption accordingly.