It's been a while since I've written about the mythical "metabolic advantage" claimed for low-carbohydrate diets. It's a subject I figured I'd already done to death, but it turns out some people just won't let up. On 13 January 2021, I received an email that read as follows:
"Anssi H. Manninen has sent this article to you from medRxiv:
I thought you might be interested in the article I found in the preprint server: medRxiv"
The email links to a preprint paper co-authored by Finnish researcher and supplement marketer Anssi Manninen (pictured above). The paper is not a report on a randomized clinical trial, nor is it a meta-analysis or systematic review of RCTs other researchers have conducted.
Instead, it is a "computational study."
That right there will tell many research-oriented readers all they need to know, but for now let's pretend computational studies don't have solid form for intellectual wankery, shameless cherry-picking of data, and irrelevant extrapolation.
Some of you may remember the name Anssi Manninen from the mid-2000s - he was (and evidently still is) a rather vocal advocate of low-carb diets hailing from Finland. Manninen describes himself as a "Finnish exercise physiologist specialising in sports nutrition and ergogenic aids" and also now lists himself as "Director of Research & Development" at a Finnish supplement company called Dominus Nutrition Oy.
Some 15 or so years ago Manninen ventured onto a nutrition chat forum I ran at the time, and began making scientifically untenable statements in support of low-carb diets and their allegedly superior fat loss effects. Some of us duly objected to his claims, and noted that decades of metabolic ward studies had failed to show greater fat-derived weight loss for isocaloric low-carb diets[1-21]. To salvage his failing argument, Manninen then cited a free-living study that showed greater weight loss among the low-carb participants, and insisted it was a metabolic ward study because the participants took home meals prepared for them as part of the study.
As you might expect, we didn't take Anssi very seriously after that.
For those who don't already know, a dietary metabolic ward study is one in which participants are housed in a research facility for the duration of a study, and allowed to eat only the prescribed diets. A free-living study is one in which participants are given instructions, and sometimes even prepared food, then sent back home. Once home, what they actually eat is anyone's guess. Even if they are given pre-prepared food, as soon as they are out of the researchers' sight there is nothing to stop them supplementing the supplied food with extra-curricular items like pizza, Oreoles and Budweiser.
Obviously, when conducting a clinical trial whose purpose is to compare the effects of different dietary regimens at isocaloric (equal) energy intakes, it is crucial to ensure the participants on the different diets are actually eating isocaloric intakes.
Any nutrition researcher who doesn't know the difference between metabolic ward and free-living studies is not someone I'm going to spend my precious time listening to. And so, until 13 January 2021, when I received the above email, I'd pretty much forgotten about Manninen. When I opened the email, my first thoughts were, "that guy's still going with this anti-carb thing? There's a global virus scam bringing the world to its knees, and he thinks I care about some low-carb paper?"
And so I ignored it.
But several days ago, I received an email identical to Manninen's above, but bearing someone else's name.
It seems someone really wants me to look at his paper.
Well, I did eventually look at it, and now I have a response - but it is not going to be very complimentary.
Manninen's paper is a non-published, non-peer reviewed pre-print co-authored with someone by the name of Francisco Arencibia-Albite, who hails from the University of the Sacred Heart, San Juan, Puerto Rico.
The pre-print is posted at the medRxiv site and titled "Macronutrient mass intake explains deferential weight and fat loss in isocaloric diets."
The authors are evidently confusing the terms "differential" and "deferential"; the latter means to show deference, to be respectful. Neither authors are native English speakers, so no big deal. However, there are other flaws in their paper that are unforgiveable, in anyone's language.
"Currently," their paper begins, "obesity treatment rests on the 'calories-in, calories-out' rule ... It maintains that body weight increases as food calories are greater than expended calories but decreases when the opposite occurs; hence, weight stability is expected at energy balance meaning that over time energy-in equals energy-out. It follows that dietary regimens with identical energy content should evoke similar amounts of weight and fat loss with only minor differences that emerge from diet’s macronutrient composition, e.g., diet-induced glycogen depletion and water excretion."
And that is exactly what decades of tightly controlled research has shown.
But Manninen and his co-author are not about to be swayed by such pesky inconveniences as scientific fact. Heck no.
They then write:
"A vast collection of evidence shows, however, that low-carbohydrate diets typically result in much greater weight and fat loss than isocaloric low-fat diets.7, 8, 9, 10, 11, 12" (Bold emphasis added)
See that string of numbers at the end of that sentence? They refer to the following studies:
7. Hall KD, et al. Calorie for Calorie, Dietary Fat Restriction Results in More Body Fat Loss than Carbohydrate Restriction in People with Obesity. Cell Metabolism, 2015; 22: 531.
8. Lean M, et al. Weight loss with high and low carbohydrate 1200 kcal diets in free living women. European Journal of Clinical Nutrition, 1997; 51: 243–248.
9. Bazzano LA, et al. Effects of Low-Carbohydrate and Low-Fat Diets: a randomized trial. Annals of Internal Medicine, 2014; 161: 309.
10. Samaha FF, et al. A Low-Carbohydrate as Compared with a Low-Fat Diet in Severe Obesity New England Journal of Medicine, 2003; 348: 2074–2081.
11. Brehm BJ, et al. Diet and a Calorie-Restricted Low Fat Diet on Body Weight and Cardiovascular Risk Factors in Healthy Women. Journal of Clinical Endocrinology & Metabolism, 2003; 88: 1617–1623.
12. Brehm BJ, et al. The Role of Energy Expenditure in the Differential Weight Loss in Obese Women on Low-Fat and Low-Carbohydrate Diets. Journal of Clinical Endocrinology & Metabolism, 2005; 90: 1475–1482.
This, ladies and gentlemen, is their "vast collection" of studies showing "much greater weight and fat loss" on isocaloric low-carb diets.
Number 7 is a most bizarre choice to cite in support of this thesis. It involved an isocaloric metabolic ward study in which participants spent only 6 days on a reduced carb intake (140g daily) and a more typical carb intake (350g daily), in random order. This is the NUSI-commissioned ward study led by NIH researcher Kevin D Hall, which low-carb believers confidently assumed would demonstrate superior results for their beloved diet. When it failed to do so, they lost their caca and rabidly turned on Hall, as if he were somehow personally responsible for the inability of low-carb diets to demonstrate greater fat loss at isocaloric intakes. While the reduced carb diet did produce more body mass loss during the very brief study periods, it was the higher carb diet that produced slightly greater fat loss, as determined by DEXA. Which means the greater weight loss in the low-carb phase likely came from fluid, glycogen and possibly lean mass (which is exactly what other short-term studies have found).
As for the rest of the studies, you don't even need to retrieve citation 8 to know it was a free-living endeavour - it's already there in the title. So this study is useless for determining the effects of isocaloric diets on weight loss, because we have no way of knowing if the participants truly followed isocaloric diets.
Studies 9, 10, 11 and 12 were also free-living studies and therefore totally inadequate for telling us what the subjects ate. Yes, they utilized such measures as brief self-reported dietary records, but there is a wealth of research showing dietary self-reporting is about as reliable as Windows 10. Underreporting and misreporting is the norm, not the exception in free-living nutrition studies[22-45].
As I throughly explained in The Fat Loss Bible way back in 2006, and again in 2012, and will again explain in any future version of the book because it remains 100% true: When low-carb and higher-carb diets are compared under truly isocaloric metabolic ward conditions, low-carb diets fail to show greater fat-derived weight loss every single time.
That's why Manninen and his co-author cite a mere five cherry-picked free-living studies that reported greater weight and/or fat loss on the former. I could easily cite 5 free-living studies that found no difference. In fact, just for shits and giggles, I'll cite twenty:
- Rumpler WV, et al. Energy-intake restriction and diet-composition effects on energy expenditure in men. American Journal of Clinical Nutrition, Feb, 1991; 53 (2): 430-436.
- Kogon MM, et al. Psychological and metabolic effects of dietary carbohydrates and dexfenfluramine during a low-energy diet in obese women. American Journal of Clinical Nutrition, Oct, 1994; 60: 488-493.
- Johnston CS, et al. High-protein, low-fat diets are effective for weight loss and favorably alter biomarkers in healthy adults. Journal of Nutrition, Mar, 2004; 134 (3): 586-591.
- Meckling KA, et al. Comparison of a low-fat diet to a low-carbohydrate diet on weight loss, body composition, and risk factors for diabetes and cardiovascular disease in free-living, overweight men and women. Journal of Clinical Endocrinology & Metabolism, Jun, 2004; 89 (6): 2717-2723.
- Sargrad KR, et al. Effect of high protein vs high carbohydrate intake on insulin sensitivity, body weight, hemoglobin A1c, and blood pressure in patients with type 2 diabetes mellitus. Journal of the American Dietetic Association, Apr, 2005; 105 (4): 573-580.
- Noakes M, et al. Comparison of isocaloric very low carbohydrate/high saturated fat and high carbohydrate/low saturated fat diets on body composition and cardiovascular risk. Nutrition & Metabolism, 2006; 3: 7.
- Johnston CS, et al. Ketogenic low-carbohydrate diets have no metabolic advantage over nonketogenic low-carbohydrate diets. American Journal of Clinical Nutrition, May 2006; 83 (5): 1055-1061.
- Truby H, et al. Randomised controlled trial of four commercial weight loss programmes in the UK: initial findings from the BBC "diet trials". British Medical Journal, Jun 3, 2006; 332 (7553): 1309-1314.
- Petersen M, et al. Randomized, multi-center trial of two hypo-energetic diets in obese subjects: high- versus low-fat content. International Journal of Obesity, Mar, 2006; 30 (3): 552-560.
- Cardillo S, et al. The effects of a low-carbohydrate versus low-fat diet on adipocytokines in severely obese adults: three-year follow-up of a randomized trial. European Review for Medical and Pharmacological Sciences, May-Jun, 2006 ; 10 (3): 99-106.
- LeCheminant JD, et al. Comparison of a low carbohydrate and low fat diet for weight maintenance in overweight or obese adults enrolled in a clinical weight management program. Nutrition Journal, Nov 1, 2007; 6 (1): 36.
- Shai I, et al. Weight Loss with a Low-Carbohydrate, Mediterranean, or Low-Fat Diet. NEJM, 2008; 359: 229-241.
- Bradley U, et al. Low-fat versus low-carbohydrate weight reduction diets: effects on weight loss, insulin resistance, and cardiovascular risk: a randomized control trial. Diabetes, Dec, 2009; 58 (12): 2741-2748.
- Demol S, et al. Low-carbohydrate (low & high-fat) versus high-carbohydrate low-fat diets in the treatment of obesity in adolescents. Acta Pædiatrica, 2009; 98: 346–351.
- Foster GD, et al. Weight and Metabolic Outcomes After 2 Years on a Low-Carbohydrate Versus Low-Fat Diet: A Randomized Trial. Annals of Internal Medicine, 2010; 153: 147-157.
- de Souza RJ, et al. Effects of 4 weight-loss diets differing in fat, protein, and carbohydrate on fat mass, lean mass, visceral adipose tissue, and hepatic fat: results from the POUNDS LOST trial. American Journal of Clinical Nutrition, 2012; 95: 614–625.
- Dalle Grave R, et al. A Randomized Trial of Energy-Restricted High-Protein Versus High-Carbohydrate, Low-Fat Diet in Morbid Obesity. Obesity, 2013; 21, 1774-1781.
- Guldbrand H, et al. Randomization to a low-carbohydrate diet advice improves health related quality of life compared with a low-fat diet at similar weight-loss in Type 2 diabetes mellitus. Diabetes Research and Clinical Practice, 2014; 106: 221-227.
- Tay J, et al. Comparison of low- and high-carbohydrate diets for type 2 diabetes management: a randomized trial. American Journal of Clinical Nutrition, 2015; 102 (4): 780–790.
- Gardner CD, et al. Effect of Low-Fat vs Low-Carbohydrate Diet on 12-Month Weight Loss in Overweight Adults and the Association With Genotype Pattern or Insulin Secretion. The DIETFITS Randomized Clinical Trial. JAMA, Feb 20, 2018; 319 (7): 667-679.
In addition to blatant cherry-picking, the Manninen and Arencibia-Albite paper is replete with mathematical equations devised by the latter that supposedly demonstrate how low-carb diets cause greater fat loss, even though ward studies going all the way back to 1935 show they don't.
The authors include graphs featuring "two hypothetical overweight 90kg adult males with identical body composition and weight maintenance energy intakes." Arencibia-Albite's formulas, they tell us, predict greater weight loss in these 90kg fellows, and this predicted weight loss corresponds with what has been shown in clinical trials.
The implication being that Arencibia-Albite's mathematical musings are bang on the money.
But those clinical trials that 'validate' Arencibia-Albite's equations just happen to be his and Manninen's small, cherry-picked selection of mostly free-living studies.
The Well-Controlled Comparison of Isocaloric Low- and High-Carb Diets that Wasn't
Later on in the paper, they again claim their predictions are validated by clinical research, this time "a well-controlled feeding study" by Kong et al involving young women. In fact, their paper relies quite heavily on the results of the Kong study.
But this "well-controlled" study was in fact a free-living, non-randomized study that relied on self-reported 3-day food diaries.
Huh? What? Uh, sorry, but after more than 15 years of debunking the same old nonsense ...
So where was I?
Oh yeah, Kong et al.
This Chinese study was not a randomized trial of low-carb and high-carb diets.
It was a study in which twenty young female participants began the study by spending four weeks on their habitual diet, before switching to a ketogenic diet for another 4 weeks. When following the keto diet, they were instructed to consume around 10% of daily energy intake from carbohydrates (approximately 50 g/d).
Now, a quick word on conducting research that qualifies as good science. In a study designed to compare two different diets, you randomly assign one group to follow one diet, and another group to simultaneously follow the other diet.
Or you have the same group of participants follow both diets in crossover fashion for a set length of time, but in random order.
What you do not do is simply switch them from their normal diet to your intervention diet. Any resultant weight loss may simply be due to the change in diet, and any accompanying short-term reductions in calorie intake due to increased satiety, restricted food choices, etc.
This is not to criticize the researchers behind this Chinese study - they did not set out to do a direct comparison trial of low- and high-carb nutrition. They simply wanted to observe what happened when the female subjects spent four weeks on a ketogenic diet. They made no claims about a low-carb diet being superior to a higher-carb diet or vice versa for weight loss, and with good reason: Their study was not equipped to make such a claim.
It is Manninen and Arencibia-Albite, evidently desperate for some supporting evidence, that are falsely portraying this study as a "well-controlled" weight loss comparison of isocaloric low- and high-carb diets.
For those interested, the women in the Chinese study maintained their weight during the habitual diet period, then lost an average of 2.9 kg of total body mass and 2% body fat after the 4-week ketogenic diet intervention. The authors did fall into the trap of claiming these results were achieved "without calorie restriction."
But the mean self-reported daily energy intake during the habitual diet period was 1,967 calories; during the ketogenic intervention, it was 1,817 calories - which indicates the participants ate less during the ketogenic diet phase. Given the well-documented vagaries of self-reporting and the degree of weight and fat loss observed, the true difference in caloric intake was no doubt even greater.
During the normal diet period, no adverse event was reported, but during the ketogenic period, the researchers received 10 complaints from seven subjects; these complaints included fatigue (five complaints), constipation (three complaints), reduced appetite (one complaint), and diarrhea (one complaint).
Things go better with carbs.
Päätelmä/Conclusión/Conclusion (this is an all-inclusive website, peoples).
The Mansinnen and Arencibia-Albite paper delivers a mirage based on a false premise.
It presents elaborate mathematical formulas that predict greater fat/weight loss on low-carb diets. The authors claim this mathematical flimflammery is validated by the results of a small handful of cherry-picked free-living diet studies.
The authors ignore free-living studies that do not support their thesis nor validate their mathematical formulas.
More importantly, they make no mention of the tightly controlled metabolic ward research that convincingly demonstrates their mathematical formulas to be tailor-made hokum. Bonafide ward studies dating back to the 1930s have repeatedly shown no difference in fat-derived weight loss between lower-carb and higher-carb diets.
Why do Maninnen and Arencibia-Albite ignore this research?
I know next to nothing about Arencibia-Albite, and therefore am not well placed to discuss his motivations. But it is abundantly clear Manninen is a devout low-carb dogmatist. And dogmatic researchers have employed all manner of methods over the years to advance their arguments under the guise of 'science.' When a bunch of clinical trials return conflicting results, dogmatists simply pick and choose the ones that support their preconceived beliefs and ignore the rest - just as Maninnen and Arencibia-Albite have done.
When randomized clinical trials unanimously fail to support an intervention, researchers instead cite hopelessly confounded prospective epidemiological studies that found a positive statistical "association" for that intervention and whatever outcome they claim it improves. What such researchers are doing is swapping out unsupportive higher quality evidence (randomized controlled trials) for supportive lower quality evidence (statistical correlations derived by using tailor-made software to dredge data obtained from totally uncontrolled, non-randomized and often hopelessly confounded population studies).
Maninnen and Arencibia-Albite don't go the epidemiological route, but they do rely on other forms of lower quality evidence. Researchers seeking to avoid inconvenient RCT results involving real live human subjects often instead resort to citing animal experiments, mathematical formulas and, more recently, 'genomic' data.
The latter two have the added bonus of sounding very 'sciency' and being beyond the grasp of many readers - the old "If You Can't Blind Them With Brilliance, Baffle Them With Bullshit" approach. Any inability to comprehend these papers is not typically the fault of the puzzled reader; rather, the problem is the mathematical formulas are convoluted bullshit that have no basis in physiological reality, while the genomic papers are often fantasmagorical exercises in irrelevant extrapolation whose results fail to hold up in controlled research in living, breathing Homo sapiens.
We saw this type of intellectual masturbation way back in 2003 in a paper titled "Thermodynamics and metabolic advantage of weight loss diets" authored by a Richard Feinman (a Professor of Biochemistry) and a Eugene Fine (a Professor of Nuclear Medicine). The paper was eagerly embraced by low-carb devotees, even though it cited a mere twelve clinical trials comparing lower- and higher-carb diets. Of the four ward studies they cited, three just happened to be the two sloppy Rabast trials and the cheating-plagued Kekwik and Pawan study (the other was a ward study by Golay which showed no significant difference in weight or fat loss). I have presented a detailed list of glaring flaws with the Rabast and Kekwik/Pawan studies in The Fat Loss Bible and elsewhere on this site, but for now I'll just reiterate that none of these three studies measured fat loss, only total body mass loss (which can include lean mass and fluid losses). Citing three poorly conducted ward studies that did not even measure fat loss to support the claim low-carb diets produce greater fat loss is, well ... stupid.
After presenting their small cherry-picked selection of mostly free-living studies, Feinman and Fine then waxed much lyrical about thermogenesis, glucogeonesis and amino acid oxidation, metabolic cycles and chemical pathways. They even presented their own "correct" thermodynamic equation that supposedly factored in the heightened thermogenesis of "low carbohydrate/high protein diets," even though reduced carbohydrate intakes have routinely failed to increase thermogenesis in controlled studies. Meanwhile, citing the thermogenic effects of high protein intakes is disingenuous on two counts: 1) there is nothing to stop one eating a high protein and high carbohydrate diet (many people do just this, I happen to be one of them); 2) the additional but small thermogenic effect of high protein diets has been repeatedly shown to be a non-event in terms of overall weight loss (something I devoted an entire chapter to in FLB).
Feinman and Fine's paper was bunkum. When I publicly pointed this out, the former took offence. That's fine (no pun intended), but when I asked why the authors ignored the multitude of ward studies showing no greater fat-derived weight loss on low-carb diets, no answer was forthcoming. Some fifteen or so years later, I'm still waiting for an answer.
And so it is with Manninen. It was also pointed out to him some fifteen or so years ago that ward studies (real ones, not free-living studies involving packed meals) repeatedly failed to demonstrate the mythical 'metabolic advantage' of low-carb diets.
Yet here he is, in 2021, still ignoring those ward studies and instead presenting a small hand-picked selection of mostly free-living studies, backed by a bunch of theoretical pseudoscience that is completely undercut by the ward research he and his co-author carefully ignore.
Some things never change.
When Hubris Meets Pseudoscience
I see at the medRxiv site Anssi has taken to calling himself "King Manninen" and one of his new hobbies seems to be attacking Kevin Hall, the same researcher whose brief ward study he and Arencibia-Albite bizarrely cite in support of their low-carb thesis.
Meanwhile, he praises Gary Taubes, the anti-carb author who created NUSI, a personal wealth enhancement vehicle dressed up as a philanthropic foundation. It was NUSI - an ultimately useless money vacuum that achieved little other than to pad the bank accounts of Taubes and his partner Peter Attia - that commissioned Hall's study, praising the NIH researcher profusely in its website description of the impending study. But when Hall's brief ward study failed to find the results the low-carb zealots were hoping for, they all scathingly turned on Hall. Never mind it was Taubes who somehow convinced hapless donors and even the taxpayer-funded NIH into funding a study that inevitably found what decades of ward trials had already found: Isocaloric low-carb diets do not produce greater fat loss.
The irrationality doesn't end there. In the introduction to their pre-print, Maninnen and Arencibia-Albite include the following passage from 19th century German philosopher Frederich Nietzche's book The Gay Science:
"The strongest and most evil spirits have so far advanced humanity the most: they have always rekindled the drowning passions – all ordered society puts the passion to sleep; they have always re-wakened the sense on comparison, of contradiction, of joy in the new, the daring, and the untried; they force men to meet the opinion with opinion, model with model [EBT vs. MBM] … The new is always the evil …”.
See the "[EBT vs. MBM]" in brackets? Mansinnen and Arencibia-Albite inserted it into Nietzche's passage themselves. EBT stands for energy balance theory, while MBM signifies their "mass balance model."
So Manninen and Arencibia-Albite are apparently citing Nietzche to show they are "evil spirits" about to advance humanity with their revolutionary new "MBM" model.
I'm not sure what these two have been drinking, but it must be strong.
Manninen and Arencibia-Albite might want to dial down the hubris and readjust their expectations. They are not going to revolutionize the world of nutrition with their new paper, even if it somehow passes peer-review and gets published (which in today's appalling scientific arena, is entirely possible). Rather than cite fancy equations that 'demonstrate' a metabolic advantage that doesn't exist (as Feinman and Fine tried in 2003), they need to cite tightly controlled metabolic ward research showing greater fat-derived weight loss on truly isocaloric low-carb diets in real live human subjects. I won't hold my breath on that, because I've lost count of the times I've already asked low-carb zealots for this very evidence ...
And before I get nasty hate mail from Finland and Puerto Rico, I should point out that I tried to ignore this paper, I really did. But if you and your supporters are going to make a point of sending me this stuff, well...
Now if you don't mind, Anssi, there's a global virus scam I'd like to continue debunking.
Prince Anthony XIV, long lost descendant of the Reggio Calabria Royal Family. Salutations also from King Ramone, royal descendant of the American Staffordshire and German Boxer clans.
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