What Diogenes Has To Say About Weight Loss: Study Investigates "Optimal" Macronutrient Compositions for Weight Loss & Maintenance

Image 1: Diogenes, a critical thinker
of the ancient world and eponym of
a European research project; a man
right after my liking, who would not tire
questioning common "wisdom".

I must forewarn you: Being part of the pan-European Diogenes Project, the study I am going to tell you about in the following is not something you can read or understand in a few minutes. Aimed at elucidating the intricate relationship(s) between Diet Obesity and Genes [the acronym DIOGENES was aptly chosen, for there is little doubt that Diogenes, if he lived today, would certainly feel inclined to debunk many of the nutritional idiocies of our age, cf. image 1], the project that is financially supported by the European Union, is literally epic. Its newest spin-off, an investigation into the "blood profiles of proteins and steroids during weight maintenance with manipulation of dietary protein level and glycaemic index" (Wang. 2011), is no exception to this rule. I will thus try my best to summarize the study design along with the most important findings, as comprehensively as possible.

From the participants of previous weight loss trials, Ping Wang from the Department of Human Biology at the NUTRIM School for Nutrition in the Netherlands, and 15 colleagues from other European institutions that cooperate under the roof of the Diogenes Consortium selected 96 overweight/obese, but otherwise healthy female subjects (age 29-49y), who had experienced a pronounced, but not extreme weight loss and/or regain in the course of previous trials. According to the weight loss, respectively regain the subjects had experienced after an initial 8-week low calorie (800-1000kcal/day) weight loss phase, the group of participants was further divided into "continued weight losers" (WL; n= 48) and "weight regainers" (WR; n= 48). All subjects were instructed to eat ad-libitum, while trying to maintain their weight at a constant level for the subsequent 6 month weight maintenance phase. Each of these groups was then further subdivided into four groups, the participants of which were instructed to consume one out of four diets that were characterized by high, respectively low protein intake and high or low GI carbohydrate content (cf. figure 1)

Figure 1: Schematic illustration of the 2x4 groups à 12 subjects whose endocrine responses during weight loss/regain after an 8-week low-calorie dietary intervention were analyzed in the study.

Despite the names of the groups, a closer look at the actual macronutrient composition consumed by the participants of each of the groups (cf. figure 2) does reveal a that the actual differences in protein intake (as measured by dietary questionnaires) in the low vs. high protein groups were modest, at best - a fundamental drawback of the study, which is also acknowledged by the authors, themselves.

Figure 2: Relative macronutrient composition of the diets of 'continous weight losers' (WL) and 'weight regainers' (WG) on low (LP) or high (HP) diets with reference to a standard 2.000kcal/day diet (calculated based data from on Wang. 2011)

As can be seen in figure 2, the difference in protein intake for the weight loss groups (LP(WL) and HP(WL)) amounts to about 23g, while the low protein weight regain (LP(WR)) group consumed only 11g less protein than the high protein weight loss group. Unquestionably, the conclusions about the effects of high vs. low protein content in the subjects' diets on the outcome of the dietary intervention would certainly have been more reliable, if the scientists had not been satisfied by these "modest differences", as they themselves describe them, but had specified an absolute or relative amount of protein the subjects in the high protein groups had to consume every day.

That being said, there were nevertheless certain differences in dietary success/failure and serum parameters that correlated well with the macronutrient compositions of the respective diets:

Figure 3: Overview of hormones and
peptides measured in Wang. 2011

• previous studies from the Diogenes Project had already established that "both a modestly higher protein content and a modest reduction in GI in the context of an ad libitum diet improve weight-loss maintenance" (Larssen. 2010); these results were confirmed in the study at hand
• in terms of the measured serum markers all groups experienced what the scientists label "a ‘return-back’ effect of the body to keep the homeostasis" in the course of the ad-libitum fed 6-month weight maintenance phase of the study, but...
• interestingly, "return-back regulation of IL-6 failed in the WR group", indicating that despite an increase in fat mass, the associated inflammatory marker remained relatively low
• on the other hand, "Leptin (LEP) and pancreatic polypeptide showed [the return-back effect] significantly more profoundly in the WR group", which would have been expected in view of the increase in fat mass these subjects experienced
• the observation that subjects who kept losing weight had "less increase in diastolic blood pressure, cholesterol, TAG [triglycerides] and glucose" corroborates the undesirable side effects of weight regain (WR)
• a slight increase in C-reactive protein (CRP; a marker generally associated with increased risk of heart diesease) in the subjects who regained weight on a high protein diet, warrants further investigation [in view of the fact that the high protein WR group consumed about the same amount of protein as its weight loss counterpart, I do yet highly doubt that the protein intake is to blame for this]

Other results worth mentioning were that while high protein intake and a low GI diet were associated with more weight loss in the weight loss group, in the weight regain group group, however, only the protein intake had a exhibited an ameliorative effects on the amount weight the subjects regained. Overall, "[t]here was no analyte [cf. figure 3] for which the fold change did significantly reflect the dietary GI level", and "for fat mass, no significant dietary effect in both groups could be detected", at all.

In figure 4 I've also compiled the data on body composition changes in the course of the weight maintenance phase [indicated by parameter 'm' as in 'maintenance'] relative to the BMI, body fat and waist circumference after the initial 8-week low-calorie weight loss interference.

Figure 4: Changes in body composition during the 6-month weight "maintenance"-phase relative to BMI, body fat and waist circumference after the initial 8-week weight loss phase; abbreviations: LP=low protein, HP=high protein; LGI=low glycemic index, HGI=high glycemic index; WL=subjects who continuously lost weight, WR=subjects who regained weight (data calculated on the basis of Wang. 2011)

In view of the quest for an optimal [I am honestly asking myself whether this even exists] macronutrient composition, mentioned in the title of this post, the most intriguiging finding of this study may thus be summarized as follows:

A "high" (remember 18%, see above) protein low-GI diet is optimal for weight loss and at least as effective to ward of weight regain as the other diets evaluated in this study

In that, the most reasonable explanations for the beneficial effects on weight loss and regain are reductions in  glucagon and insulin, the promotion of an anabolic state and lipolysis via the upregulation of testosterone and generally lower plasma levels of plasminogen activator inhibitor 1, a well known modulator of adipose tissue development on a high protein, low glycemic index diet.