Monday, September 19, 2016

Two-Year Study Seems to Suggest: 'Ketogenic Diet' Doubles Weight, Triples Fat Loss vs. Std. Diet, but in Reality...

Unfortunately, this is not a photo of the "ketogenic diet" meals the subjects were served in exactly 2 out of 24 months of the study... ah, and the various supple-ments they were taking to make up for nutrional deficits are also missing.
There are two reasons why the number of studies on the long-term effects of ketogenic diets on health and body composition is still limited. The obvious reason is that it takes time to conduct these studies. This is yet not the full truth, though. After all, conducting a "low fat"-diet study will also take time and we have hundreds of long-term studies, here.

Unfortunately, this is where reason #2 comes into play: Not too long ago you would probably have had problems to get funding and/or to even get past the ethics committee of your institution with a study in which overweight or obese subjects were supposed to be exposed to a "high fat" and or "high protein" diet that could "jeopardize their health".
You know, high-protein diets are safer than people say, but there are things to remember...

Practical Protein Oxidation 101

5x More Than the FDA Allows!

More Protein ≠ More Satiety

Protein Oxidation = Health Threat

Protein Timing DOES Matter!

More Protein = More Liver Fat?
Over the past decade, however, the number of low carb dieters and researchers who back the notion of "eating more fat to lose fat" has been growing continuously. You cannot say that the tides are turning, yet, but the existing experimental evidence which shows that low carb or ketogenic diets are effective, at least in the short to medium term, as a tool to fight obesity (Bueno. 2013) is convincing enough to get permission and financing (in this case by a Spanish protein supplement producer who funded the study and supplied the protein powder used in the study) for long-term keto studies.

Against that background, the latest study by Basilio Moreno et al. (2016) would not be an exception to the role but still one out of a selected few studies that assessed the effects of a ketogenic diet on glycemia, lipidemia and body composition (esp. visceral fat) over 2 years and compared the outcomes to both, a non-dieting control and a regular low calorie control group (LC), the scientists describe as follows (Moreno. 2016):
  • Low-calorie control (LC) - The standard LC diet was an equilibrated diet that had a caloric value 10 % below the total metabolic expenditure of each individual. The total metabolic expenditure was calculated from the basal metabolic expenditure (based on the formula FAO/WHO/UN) multiplied by the coefficient of activity, which was calculated according to the physical activity of each participant. The calories provided to this group ranged between 1400 and 1800 kcal/day. The ratio of macronutrients provided was 45–55 % carbohydrates, 15–25 % proteins, and 25–35 % fat  in addition to a recommended intake of 20–40 g/day of fiber in the form of vegetables and fruits. A ratio exchange model was followed
  • Very low-calorie ketogenic diet (VLCK) - The VLCK diet group followed a diet according to a commercial weight loss program (Pronokal method) based on a high biological value protein preparations diet and natural foods. Each protein preparation contained 15 g of protein, 4 g of carbohydrates, and 3 g of fat, and provided 90–100 kcal. This method has three stages: the active stage, the re-education stage, and the maintenance stage (Fig. 1). The active stage consists of a very low-calorie diet (600–800 kcal/day) that is low in carbohydrates (< 50 g daily from vegetables) and lipids (only 10 g of olive oil per day). The amount of high biological value proteins ranges between 0.8 and 1.2 g per each kg of ideal body weight, to ensure that it meets minimal body requirements and prevents the loss of lean mass. This method produces three ketogenic phases. In phase 1, the patients eat high biological value protein preparations five times a day, and vegetables with a low glycemic index. In phase 2, one of the protein servings is substituted with a natural protein (e.g., meat or fish) either at lunch or at dinner. In phase 3, a second serving of a low-fat natural protein replaces the second serving of a biological protein preparation.
    Figure 1: Dietary intervention for the VLCK diet. The duration of the different stages depends on the targets and the clinical decision of the physician in charge. The duration of stage 1, i.e., on ketosis, was less than 2 months, stage 2 ranged from 5–6 months and stage 3 was until 24 months (Moreno. 2016).
    Throughout these ketogenic phases, supplements of vitamins and minerals, such as K, Na, Mg, Ca, and omega-3 fatty acids, were provided in accordance with international recom-mendations. This active stage is maintained until the patient achieves most of the weight loss target, ideally 80 %. While the ketogenic phases were variable in time depending on the individual and the weight loss target, they lasted between 45–60 days in total.

    In the re-education stage, the ketogenic phases were ended by the physician in charge of the patient based on the amount of weight lost, and a low-calorie diet was initiated. At this point, the patients underwent a progressive incorporation of different food groups and participated in a program of alimentary re-education to guarantee the long-term maintenance of the weight lost (Fig. 1). The maintenance stage, which lasted 2 years, consisted of an eating plan balanced in carbohydrates, protein, and fat. Depending on the individual, the calories consumed ranged between 1500 and 2000 kcal/day, and the target was to maintain the lost weight and promote a healthy lifestyle.
If you take a closer look at the information about the diets of the LC and VLCK group, however, you will realize that this is not a ketogenic diet as you would (rightly) expect it to be used in a study that uses the phrase "ketogenic diet" in the title, already (that's the case for all stages of the intervention, even though it is visible in Figure 1 only in stage 2+3). Rather than that, stage 1 of the intervention makes use of a supplement supported starvation diet that induced a "mild ketosis" (because of its lack of energy, not a high fat and low carbohydrate content). This stage is then followed by an 8-month transition diet (that's not ketogenic either) and a 14-months regular diet follow-up and thus no fair comparison of the two diet concepts (keto vs. mixed or low-fat diet). Eventually, the diets differed not just in their nutrient composition but represent completely different dieting philosophies:
  • VLCK - "cut rapid- and severely and try to maintain afterward" 
  • LC - "lose weight slowly & continuously w/ lifestyle change + minimal deficit"  
Against that background and in view of the fact that the LC "control" diet was on top of that exactly what (hopefully) no SuppVersity reader would ever do to lose body fat (too little energy from protein and a deficit of only 10%, of which previous studies show that it is more than just suboptimal for weight loss - especially in the obese), you should keep this 'lack of equal playing fields' in mind, when evaluating the differential effects of the diets on the 45 of initially 79 patients (mean age 45 years; mean BMI 35 kg/m², mean waist circ. 110 cm) from the Obesity Unit at the Hospital Gregorio MaraƱon of Madrid who enrolled in Moreno's study.
Figure 2: Evolution of weight loss after initiation of treatment and during 24 months of follow-up. Data from the completers groups are presented and the data obtained through the ITT analysis are also shown. LOC last observation carried forward, BOC basal observation carried forward, MI multiple imputations. *p < 0.001 difference between groups; ¥ < 0.001 differences with respect to baseline values (Moreno. 2016).
The fact that the VLCK patients lost significantly more weight, and even twice the amount of weight the LC group lost, can, for the previously mentioned reasons, hardly be considered surprising. After all, the subjects in the VLCK group were in a hell of a lot greater deficit. And that was not just the case in the initial ~2 month starvation phase, but also during the major part of the 5-6 months-long "dietary re-education" stage towards the end of which the subjects' weight started to increase again and that despite the fact that they were still consuming much less energy than their peers in the LC group.
Don't be tricked by misinterpretations of this study! I am not sure if this is / was on purpose, but by not comparing the prescribed energy intake the LC and VLCK group anywhere in the paper, the scientists made their study extremely open to being misinterpreted by people with an agenda.

Estimated mean cumulative energy intake in the LC and VLCK groups over those 8 months of the study during which the subjects actually lose weight and cor-responding deficits in % (the figures are based on the assumption that the subjects needed only 1800 kcal per day for weight maintenance) if that was more, the VLCK advantage would increase significantly).
Even if we assume for simplicity a mean dietary intake of 1,800 kcal at maintenance - which is a rather conservative estimate in view of the fact that the subjects were 'heavy' and of both male and female sex - the LC group (~388,800 kcal in the first 8 months) would have been consuming approximately 56% more energy than the VLCK group (~249,000 kcal in the first 8 months). If you still insist that the study shows the superiority of low carb dieting, you must not have read the full-text and/or ignored the scientists' own conclusion which reads "a very low-calorie-ketogenic diet was effective 24 months later, with a decrease in visceral adipose tissue and a reduction in the individual burden of disease" and says nothing of a superiority of one diet over the other (for a good reason).
The reason it is still worth to take a look at the graphs in Figure 3 is thus not to see how well a "ketogenic diet" works (in fact, by know you should have realized that a "ketogenic diet" as you probably had it in mind when you first read about this study here or elsewhere was not even involved in this study) compared to a "regular" diet. No, the reason is to see how well the commercial PronoKal® program, which - and you got to really scrutinize the "privacy policy" small print at the PronoKal® website to find that out - happens to be belong to Protein Supplies the sponsor of the study, did in comparison to wasting one's time with the worst imaginable but still often recommended weight loss approach you will find.
Figure 3: Lean body mass (LBM) and fat mass (FBM) loss in the two groups over time (Moreno. 2016).
So, "yes!", the program worked, but how impressive is a 19.1 kg fat loss on a 42%+ (see red box) deficit you run over an 8-months period (the must be said for the reduction in visceral fat, which is particularly highlighted in both and abstract of the full-text and the reason the main reason the scientists hail the PronoKal® program as being effective to "reduce the disease burden") ?

Still impressive? Ok. So how practically relevant is it if we all know that this diet is not sustainable and it takes only 14 months on a still very strict "balanced maintenance diet" to regain 10.3 kg of the 19.1kg (i.e. 54%) without regaining any of the previously lost lean body mass? I refuse to answer this question, but I think I have given you all the information that's necessary to answer it for yourselves.
It's not that VLCK diets would not have benefits. I have even written extensively about them in previous articles. Articles such as "450-700kcal/day Diet Cuts 7% Body Fat in 3 Weeks - Only if You go Keto, Though, it Will also Increase Lean Mass by 4%" (read the full article) - That they double the weight loss, however, is unheard of in fair and well-designed scientific studies.
Bottom line: I think I have said enough about the study at hand for you to realize that it does not show the superiority of low carb or ketogenic dieting in either the short or long term. Rather than that it is yet another example, where only a close analysis of the full-text will prevent you from falling for accidental or purposeful misinterpretations of scientific research... sponsored scientific research, in the case of which I cannot avoid the impression that it may have looked differently if the scientists' goal had not been "to evaluate the long-term effect of a VLCK diet as part of a commercial weight loss program (Pronokal method), compared with a standard LC diet on decreasing adiposity in obese patients" (Moreno. 2016), but to simply conduct the study we are all waiting for: a fair and controlled (not observational) comparison of the efficacy of effectively designed whole-food based energy-equated ketogenic vs. regular diets in the long run (ideally 24 months+) | Comment on Facebook!
  • Bueno, Nassib Bezerra, et al. "Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials." British Journal of Nutrition 110.07 (2013): 1178-1187.
  • Moreno, Basilio, et al. "Obesity treatment by very low-calorie-ketogenic diet at two years: reduction in visceral fat and on the burden of disease." Endocrine (2016): 1-10.