One of the most common critiques raised against the use of VLCKD is the so-called “yo-yo” effect, i.e.
, the weight regain cycle [11
]. In other words some opponents and doubters of VLCKD suggest that any beneficial effects are only transient. There is no universally accepted definition of “successful weight loss maintenance” following a diet but a reasonable candidate would be that proposed by Wing and Hill in 2001, which defines it as “individuals who have intentionally lost at least 10% of their body weight and kept it off at least one year” [27
]. The criterion of 10% is chosen for its well documented effects in the improvements in risk factors for diabetes and cardiovascular disease, while the one year duration criterion was proposed in agreement with the USA Institute of Medicine [28
]. The data from our present study suggest that two brief periods of a “Mediterranean” variant on the VLCKD theme (which we call KEMEPHY) are able to induce significant weight and body fat loss that was maintained for at least one year. In particular the weight loss reached at six months, after the second cycle of VLCKD, was maintained, without weight regain, over the subsequent six months of normocaloric Mediterranean nutrition. The mechanisms underlying the effects of VLCKD on weight loss is still a subject of debate. One hypothesis is that the use of energy from protein in VLCKD is an “expensive” process for the body and so can lead to a “waste of calories” and therefore increased weight loss compared to other “less expensive” diets [29
]. During the first phase of a VLCKD 60–65 g of glucose per day are needed by the body, 16% of this is obtained from glycerol whilst the major part derived via gluconeogenesis from proteins, of either dietary or tissue origin [30
]. Gluconeogenesis is an energy-demanding process calculated at approximately 400–600 Kcal/day (due to both endogenous and food source proteins [29
]. There is however no direct experimental evidence to support this intriguing hypothesis, on the contrary a recent study reported that there were no changes in resting energy expenditure after a VLCKD [31
]. Some authors claim instead that the results obtained with ketogenic diets could be attributed to a reduction in appetite due to higher satiety effect of proteins [29
] or to some effects on appetite control hormones [10
]. Other authors suggest a possible direct appetite suppressant action of the ketone bodies [33
]. But regardless the mechanisms involved in the weight loss effects of KD, there is substantial agreement about its medium term efficacy. Nevertheless, as stated before, one of the major problems in weight control is the prevention of weight regain. In the present study the majority of subjects maintained >10% weight loss at 12 months but we detected 8 subjects in which the weight loss was not maintained at all (Figure 3
); these subjects were included in the final statistical calculations but the post dietary analysis showed that they were not compliant with nutritional guidelines given for the Mediterranean diet period. These subjects returned to their previous nutritional habits (“junk” food, high glycaemic index, etc
.) with a mean “real” daily intake of 2470 Kcal rather than the prescribed 1800 Kcal. Hence the compliance to this one year protocol was 88.25% in accordance with previous data [14
]. Beyond the most obvious cause of weight regain, i.e.
, a return to previous “unhealthy” habits, the physiological basis of weight regain appears to be complex [12
]. It is reasoned that the maintenance of weight loss is difficult due to many factors including reduced resting metabolic rate (RMR), insulin & leptin resistance and changes in the levels of several hormones involved in the homeostatic regulation of body weight [35
]. RMR could be affected by the loss of muscle mass due to an inadequate protein intake during dieting. The suggested daily protein consumption is around 15% in a classical hypocaloric Western diet of about 1200 Kcal/day so the actual protein content will be approximately 45 g (180 Kcal; 4 Kcal/g). Hypothesizing a body weight of 70 kg this daily protein intake will be 0.64 g per kilogram of body weight which is a possible cause of muscle loss and consequent reduction of resting energy expenditure. The VLCKD on the other hand appears not to influence (either positively or negatively) the basal energy expenditure, but recent data showed that it could improve fat oxidation and therefore lower the respiratory ratio [31
]. Regarding hormonal influences on weight regain a possible explanation involves a long-term increase in orexigenic signals. Sumithran and co-workers showed that a very low calorie diet causes a persistent elevation of the circulating mediators of appetite that encourages weight regain even one year after initial weight reduction [35
]. On the other hand it has been demonstrated that a ketogenic diet has only a minor effect on ghrelin levels and that the subjective ratings of appetite were lower when participants were in a state of physiological ketosis [10
Changes in weight (% of change) of each subject (t6 compared to t0). Basal value is represented by the line zero. Each circle represents a single subject.
We have to consider that there are some concerns among physicians and nutritionists about various aspects of VLCKD [37
]. The main proposed risk of VLCKD is possible kidney damage due to high levels of nitrogen excretion during protein metabolism which can cause an increase in glomerular pressure and hyper-filtration [30
]. But there are conflicting results: some author suggest the possibility of renal damage [38
] based on results from animal studies whilst others, looking at both animal models, meta-analyses and human studies suggest, on the contrary, that even high levels of protein in the diet do not damage renal function [40
]. In subjects with intact renal function higher dietary protein levels have been reported to cause some functional and morphological adaptations but without negative effects [42
]. Given the inconsistency of the evidence, a cautious approach is warranted in subjects with renal insufficiency, including sub-clinical, and with kidney transplant patients. Although it should also be considered that VLCKD is not necessarily a “high protein diet” (it may be higher in proportion, but not in actual content). Moreover recent research suggests that ketogenic diets may even cause a regression of diabetic nephropathy in mice [43
] and that a VLCKD had no negative effects on renal function in Type 2 Diabetics. With regards to possible acidosis during VLCKD, since the concentration of ketone bodies never rises above 8 mmol/L [44
] this risk is virtually nonexistent in subjects with normal insulin function. On the other hand there is a large amount of evidence for the benefits of Mediterranean nutritional approach on many health related outcomes. The Mediterranean diet is associated with a longer life span [45
], lower rates of coronary heart disease [4
], hypercholesterolemia [46
], hypertension, diabetes and obesity [47
]. But is difficult to isolate the “healthy” constituents of the Mediterranean diet, since it is not a single entity and varies between regions and countries. All things considered there is no “one size fits all” dietary recommendation and for this reason we have tried to merge the benefits of these two approaches: the long term “all-life” Mediterranean diet coupled with brief periods of a metabolism enhancing ketogenic diet.