Response to Freedhoff and Hall – the differences between diets do matter.

In the latest Lancet, Yoni Freedhoff and Kevin Hall have an opinion piece about diet trials, in which they argue that it’s not helpful to know that an ad lib low-carb diet results in more weight loss than a calorie-restricted low-fat “dietary guidelines” type diet, because the weight loss differences are not clinically significant, a claim which we think is both false, and overlooking other benefits of carbohydrate restriction.[1]

They then go on to ask that more effort go into identifying ways to ensure that people can adhere to diets long term, a reasonable request and something we’re very much interested in ourselves. However, they spoil this a bit by talking about “hype” (short for hyperbole) and “society’s endless parade of fad diets”. If you want to improve adherence to diets and you think that there is little to choose between them, why use the word “fad”, which is normally used to devalue people’s dietary choices?
Further, is there even an endless parade of diets these days? Aren’t there a just few variations on and recombinations of the same timeless themes, such as vegan or vegetarianism, calorie restriction, carbohydrate restriction, ancestral, and so on? The only really original idea is fasting, yet this ancient therapy only seems original because we’ve just been led through such an intensive era of round-the-clock eating.

Freedhoff and Hall concentrate their argument on one trial, the DIRECT study (sometimes better known as Shai et al.) which was a 24-month workplace intervention in Israel, with ad lib low-carb, low-fat calorie restricted, and Mediterranean diet calorie restricted arms. “The low-carbohydrate, non–restricted-calorie diet aimed to provide 20 g of carbohydrates per day for the 2-month induction phase and immediately after religious holidays, with a gradual increase to a maximum of 120 g per day to maintain the weight loss…the [low carb] participants were counseled to choose vegetarian sources of fat and protein and to avoid trans fat. The diet was based on the Atkins diet.” The Mediterranean diet (at 40% fat, mainly from olive oil and nuts) was based on a 2001 book by Walter Willett and PJ Skerrett, and the low-fat diet was based on American Heart Association dietary guidelines. All dieters had access to the same food in the workplace cafeteria, but the food suitable for each different diet was colour coded.
In this study, people in the low carb group (not very low carb after induction, it varied between 87g/day at 6 months and 120g/day reported CHO intake over the first 12 months) lost on average 1.8 Kg more weight than the low fat dieters overall.[2]
Well as Freedhoff and Hall say, that’s not a lot of weight in the grand scheme of things. So does it support their claim that we should stop caring about the results of these studies?
Not so fast. The average weight loss includes all the people who drop out of the study; this is “intention to treat” (ITT) analysis, designed to keep the randomisation of baseline characteristics stable.
But what you might want to know if you were choosing a weight-loss diet, is, what will happen to me if I follow the diet? There were more drop-outs (22% vs 10%) in this study in the low carb arm, who found it hard to resist the biscuits and cakes in the cafeteria (interestingly, this caused their intake of saturated fat to increase over the study, even as their total fat intake went down), and self-reported complete adherence to low-carb was 57% at month 24.[3] The superiority of the low carb diet in DIRECT includes the effect of including this higher drop-out rate, and those extra cakes and biscuits. The per-protocol analysis only gives us a stratified comparison of completers vs non-completers (i.e. minus drop-outs, but including those with weak adherence to diets) at 24 months, but we do know from other studies that when non-completers are excluded, the long-term difference between diets at 12 months becomes larger.[4]

ITT

So compliance is important, sticking to the diet is critical of course, but what diet you stick to matters more than Freedhoff and Hall are saying. In the DIRECT study, people who completed 24 months of the low-carb diet lost a mean 5.5 +/- 7.0 Kg, and those who completed the low fat diet lost 3.3 +/- 4.1 Kg. The biggest loser in the DIRECT study lost 35% of their body weight, but all we know about the most successful dieters is, that they weighed more at baseline, lost weight more rapidly in the early stages, and ate a bit less protein and cholesterol at baseline (but overall the protein intakes in this population were, and remained, quite high). Rapid weight loss early in a diet is usually associated with success, and of course it’s a feature of the ketogenic diet, or the induction phase of the Atkins diet here.

But wait, there’s more. Weight loss isn’t the only effect of diet, and overweight people often suffer from increased cardiometabolic risk owing to insulin resistance and the metabolic syndrome.

Freedhoff and Hall for some reason don’t mention this, but it’s the evidence we have about the “long term safety” of any diet. In all parameters the ad lib low carb diet does better than the calorie-restricted low-fat diet, even at 24 months, and even including the drop-outs.

“Among the participants with diabetes, the proportion of glycated hemoglobin at 24 months decreased by 0.4±1.3% in the low-fat group, 0.5±1.1% in the Mediterranean-diet group, and 0.9±0.8% in the low-carbohydrate group. The changes were significant (P<0.05) only in the low-carbohydrate group (P=0.45 for the comparison among groups).”[2] In fact, as far as we know, carbohydrate-restricted diets are the only diets that can produce some of these benefits without weight loss.[5]

There’s a curious extra point in the chart below – LDL rose slightly at 6 months in the low-carb arm, when adherence was good and polyunsaturated fat intake was high, and dropped at 24 months when polyunsaturated fat intake decreased and carbohydrate, but also saturated fat, intake increased.

Shai markers

But wait, there’s more. Something else that Hall and Freedhoff didn’t mention is the very long-term effects of this diet trial, because there was a four-year follow-up study. And the results here are very interesting, because there is less of a rebound effect for the ad lib low carb diet and the Mediterranean diet than for the low-fat, calorie restricted AHA diet.[6]

Shai figure 1
In the low-fat diet group (which had the fewest drop-outs) most of the improved metabolic parameters, including weight, are back to baseline levels. In the low-carb group, weight and the LDL/HDL cholesterol ratio are still improved. This is four years after the end of a 2-year study – six years in all. Quite a different result from Hall’s Biggest Loser study, where severe rebound weight gain from CICO “eat less move more” energy restriction was the order of the day.[7]

After the completion of intervention, the participants were invited once a year to the clinic for a regular check-up and were encouraged to pursue a healthy diet. Although diet-group color coding and nutrition labeling in the workplace cafeteria were stopped at the end of the intervention, the cafeteria continued to serve suitable meals according to the guidelines of the 3 diets, suggesting that the workers could still consume their specific dishes, which continued to be regularly served, as they were during the trial. We did not continue with the dietary sessions or any other activity encouraging adherence. We used one question: Are you still dieting? The question had three possible answers to choose from: 1. “Yes, with my original diet” 2. “Yes, but I switched to another diet” 3. “No, I am not dieting”. No differences were observed in response to this question between the 3 assigned diet groups (p=0.36).

 

Perhaps there are a few people in this group who were so happy with their results that they stuck with the low-carb diet for 6 years, and their results are carrying the rest – or perhaps the 2 years of low-carb diet (or the 2 months of ketogenic dieting) had lasting benefits. These questions weren’t really answered by the questionnaire quoted above, which kind of refutes Freedhoff and Hall’s suggestion that we have nothing more to learn from diet comparisons. Good post hoc analysis of the data from weight loss trials can seek to develop further hypotheses about what baseline markers, characteristics, and responses predict success, and that should inform the design of further trials and interventions. It’s also possible to tweak the diets to improve them for both effect and ease of compliance – (e.g. what if the AHA diet had been lower-GI, the Med diet lower carb, and the low-carb diet lower carb, with more Mediterranean and real food elements? Something like this probably went on during the 4-year follow-up among the people still interested in the diets).
But in the meantime, we needn’t let ourselves get confused about how to proceed.

As Prof Richard Feinman says, “remind me again why we have a medical science literature?” Comparative trials of diets and drugs are designed and published so that we know what is the most effective option between two or more choices for any given diagnosis. The intention is that the best treatment, determined by experiment, will be the one to be offered first. The patient may not like it, or it may not work, in which case it will be time to try something else, but the evidence is there to inform the discussion.

Instead we are stuck in this Catch 22 where the evidence about the best treatment for overweight and diabetes, collected over decades at great expense, is ignored (or worse) because its results contradict cherished beliefs about (in this case) the pre-eminence and equivalence of the calorie, or (at other times) the health effects of saturated fat.

Fortunately some people are brave enough to follow the existing evidence while applying themselves to solving the question of adherence. David Unwin and colleagues in the UK have worked on the psychological aspects of motivating and supporting people in low carb diets for type 2 diabetes and NAFLD with great success,[8] and recently a multicenter LCHF approach in Canada has also reported good adherence and impressive results.[9]

Canada

A thought experiment

The DIRECT study had no control group, i.e. no group of people from the same population eating a normal (whatever they are normally eating)  diet ad lib.

Imagine there was a fourth arm randomised to an ad lib version of one of the 3 diets.
Without calorie restriction, it seems less likely that the AHA-approved, last-year’s dietary guidelines diet would have made any difference from baseline. It’s possible that nothing would have improved and plausible that things would have continued to get worse overall.
Without calorie restriction, it’s likely that the Mediterranean diet (the modern, updated dietary guidelines diet) would still have been better than the AHA-approved, last-year’s model dietary guidelines diet.There may well have been some smaller improvements, and things would be unlikely to get worse.

Now imagine an ad lib version of the LCHF diet (the controversial, alternative-dietary guidelines diet). The results would still be exactly the same, because the experimental diet was ad lib.

[1] Freedhoff Y, Hall KD. Weight loss diet studies: we need help not hype. The Lancet , Volume 388 , Issue 10047 , 849 – 851.

[2] Shai, I, Schwarzfuchs, D, Henkin, Y et al. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med. 2008; 359: 229–241

[3] Greenberg, I, Stampfer, MJ, Schwarzfuchs, D, and Shai, I. Adherence and success in long-term weight loss diets: the dietary intervention randomized controlled trial (DIRECT). J Am Coll Nutr. 2009; 28: 159–168

[4] Feinman RD. Intention-to-treat. What is the question? Nutr Metab (Lond). 2009 Jan 9;6:1. doi: 10.1186/1743-7075-6-1. Full text:
https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/1743-7075-6-1

[5] Gannon MC, Nuttall FQ. Control of blood glucose in type 2 diabetes without weight loss by modification of diet composition.  Nutrition & Metabolism 2006 3:16 DOI: 10.1186/1743-7075-3-16. Full text:
https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/1743-7075-3-16

[6] Schwarzfuchs D, Golan R, Shai I. Four-year follow-up after two-year dietary interventions. N Engl J Med. 2012 Oct 4;367(14):1373-4. doi: 10.1056/NEJMc1204792.
Full text: http://www.nejm.org/doi/full/10.1056/NEJMc1204792

[7] Fothergill, E, Guo, J, Howard, L et al. Persistent metabolic adaptation 6 years after “The Biggest Loser” competition. Obesity (Silver Spring). 2016; DOI: http://dx.doi.org/10.1002/oby.21538 (published online May 2.)

[8] Unwin DJ, Cuthbertson DJ, Feinman R, Sprung VS (2015) A pilot study to explore the role of a low-carbohydrate intervention to improve GGT levels and HbA1c. Diabesity in Practice 4: 102–8. Full text:
http://www.diabesityinpractice.co.uk/media/content/_master/4311/files/pdf/dip4-3-102-8.pdf

[9] Mark S, Du Toit S, Noakes TD, Nordli K, Coetzee D, Makin M, Van der Spuy S, Frey J, Wortman J. A successful lifestyle intervention model replicated in diverse clinical settings. S Afr Med J. 2016 Jul 3;106(8):763-6. doi: 10.7196/SAMJ.2016.v106i8.10136.
full text: http://samj.org.za/index.php/samj/article/view/10136/7528

16 comments

  1. Prof Grant:

    Thank you so much for this analysis of
    Freedhoff and Hall’s disingenuousness.

  2. Freedhoff and Hall’s ideas have atual victims. They should be ashamed.

  3. All of this needs to be reexamined in light of Salk institute’s lab time restricted feeding research.
    Does 16 hours of fasting time and 8 hours of feeding produce better results? Keto and time restricted feeding? Read the Salk institute papers from doctor pandas lab.

    1. I agree; I think the next generation of clinical diet trials will be of low-carb interventions with intermittent fasting advice, instead of ad lib LCHF, vs calorie-restricted, low-fat, modified fat, low-GI diets.

  4. Adherence or compliance! Look at doctor pandas lab work time restricted feeding and compliance. Forget Hall s opinions. Use the Salk smart phone application and track 1000 or 10;000 or a million people what when and how much they eat of keto, sad, dean Cornish Paleolithic cheaper and more useful in my opinion.

  5. […] Response to Freedhoff and Hall – the differences between diets do matter. – The average weight loss includes all the people who drop out of the study … or the induction phase of the Atkins diet here. But wait, there’s more. Weight loss isn’t the only effect of diet, … […]

  6. […] Prof. Schofield: Response to Freedhoff and Hall – the differences between diets do matter […]

  7. What a clinical trial usually lacks is what a great teacher must always have. Enthusiasm.
    You must have committed enthusiasm. Randomly assigning someone to a “group” is not enthusiasm. It’s artificial.
    I’ve done low-fat high carb for most of my adult life, following the criminal guidelines which I learnt about 4 years ago, have no scientific basis. I was a doctor, and if I bought them, what chance did the man in the street have?
    My father was fat all his adult life from when he quit football as were all his family, except his father. His mother and one brother died of diabetes type 2 as did a nephew.
    I first grew a belly at about 23 and I battled with my weight all my adult life. My default weight from the age of 30 on was about 100kg. During this period I cycled a huge amount and I could get it off by starving myself and cycling huge amounts, but if I got injured etc., it would always come back to the same weight. At age of 27 I lost 42 on a low fat diet only to put it all back on immediately. I was famished.
    In 2012 I quit all sweet things and lost 20lb and when I began to regain a little I went LCHF on New Year’s day 2014. End of problem. Now wgt stable at 82kg for more than two years. Hunger no longer a problem. Feel very well and energetic.
    What’s my secret?
    I decided at the start that there would have to be no cheating. My daily carbs max at 50g. Occasionally I might stray up to 70g, but next day 30g. I actually seek fatty meat, eat tons of cheese, Greek Yoghourt etc.
    I contend that an enthusiastically promoted and supported wgt loss programme based on low carb has the best longterm chance for lonterm weight maintenance. It has to be jigged for the individual of course and in this respect, a glucometer is valuable. In this respect, I was wary about eating turnip (British call it swede, Americans Rutabaga) but on testing found that it doesn’t impact my blood sugar, even in generous quantities. There are individual reactions to particular foods, probably due to the microbiome, as shown in Israeli research.

    1. Ironically, I think opposition to LCHF has been a great motivator for many. They love “sticking it to the man” and proving the experts wrong.
      I think the exclusive focus on weight loss from Freedhoff and Hall is very much a mistake.
      In my own case, LCHF fixed multiple metabolic, digestive, and immunological problems, but I gained weight, because I was underweight.
      Two of my friends watched their weight melt away while they remained inactive and really enjoyed the food. Sure they could lose interest and (slowly) regain the weight, but if so they have some idea what to do about it now, and their health will have improved for some time to come.
      My other friend hasn’t lost any weight on LCHF, but keeps restricting carbs because she feels fitter, has more energy, and doesn’t get sick as long as she does. And sometimes not gaining weight is also an important goal.

  8. A mountain made out of a 2kg molehill.

    As someone with experience on calorie restricted cyclical ketogenic diets, I can confidently say that I could drop 4-5kg in water in a day by running a ketogenic diet. I could start tonight and finish peeing out the remainder of that water by tomorrow night.

    So, if the low carbers maintained their low carbohydrate status, 2kg in lower bodyweight might actually indicate weight gain.

    Even if it didn’t, it’s such a marginal loss that it cannot possibly mean that carbohydrate restriction is somehow the cure, either clinically or in terms of the dietary guidelines, for obesity.

    As Freedhoff and Hall put it in their conclusion:

    “Therefore, we need to increase our efforts to understand the individual differences between patients that have an effect on diet maintenance and prevent its erosion. Studies should determine how to target effective diets to individual patients,12 as well as improve our understanding of the real world considerations that impinge on patients’ abilities to sustain healthy dietary changes,13 such as those wrought by the food environment, socioeconomic factors, cooking skills, job requirements, medical comorbidities, caregiving responsibilities, and many more. After all, as with every chronic disease, successful obesity management requires lifelong treatment and there is a pressing need to help patients navigate day-to-day realities in the face of maintaining a permanent and intentional behaviour change. We also need to better understand how family, community, and society as a whole can help support and sustain healthy lifestyles.

    Fewer resources should be invested in studying whether or not a low-carbohydrate diet is marginally better than a low-fat diet, or whether intermittent fasting provides marginally better short-term outcomes than a so-called Paleo diet. Crowning a diet king because it delivers a clinically meaningless difference in bodyweight fuels diet hype, not diet help. It’s high time we started helping.”

    I’m a big advocate of pluralism in nutrition science. I support research on low carbohydrate diets. I am against the American Heart Association dietary recommendations. I find the Dietary Guidelines for Americans shameful. I was a successful Paleoer and low carber in my teens and twenties. I defended Nina Teicholz against unfair attacks by David Katz and corresponded with her at length. I’ve had links to posts on my website retweeted many times by prominent members in the low carbohydrate community, including Tim Noakes; I’ve exchanged emails with David Ludwig; I chat with Stewart Mclean all the time over at the growing Paleo forum. I love all of these people.

    And I feel as exasperated as Freedhoff and Hall apparently do. With a 2kg loss, I find it self-evidently proven that low carbohydrate diets are not going to be anything but a minor tool of passing importance in the fight against obesity and poor health. The issue in obesity is our food environments, culture, education, advertising, and overavailability of garbage.

    Studies like DIRECT prove one thing. That we’re going to have to think a lot deeper and a lot more seriously than half-assed minor changes in individual dietary macronutrient composition. It’s not the answer. Freedhoff knows it and virtually every educated person in the nutrition community knows it. Even Ludwig, after a book filled with low carbohydrate advice, admits in the final chapter that the reason we’re so fat today is our food environment–implying that low carbohydrate diets do not address root causes.

    I love the research on low carbohydrate diets. I hate that they are touted as the solution. They are not, and pretending otherwise feeds the problem no less than the Dietary Guidelines or the American Heart Association. Cholesterol as a target of food activists has been replaced by insulin. Saturated fat by carbohydrate. And the pendulum keeps swinging without moving a damn whit.

    I’m sitting here waiting for people to get serious. Until then, keep flailing about. When you want to get serious, let’s talk about what we can really do. It ain’t gonna be changing one macronutrient. If we want to help prevent obesity, we’re going to have to overturn a lot more than that. The molehill that is DIRECT is scientific proof of that. Or, you could keep celebrating 2 kg–which, potentially being water weight, may provide one of the best metaphors for the low carb movement’s insubstantiality.

    1. Hi Kevin,

      you make some fair points and we’re certainly in favour of pluralism – but pluralism doesn’t mean anarchy, an anything goes approach where evidence isn’t ranked. Sure the food environment is vital – when it comes to causality – but at a first approximation refined carbohydrate foods make up the environmental damage there. And legislating the food environment is a big target for any individual; the food environment in their kitchen is the one they can control.
      At a first approximation, throwing out carbs and seed oils improves the food environment mightily, because every rubbish food has these as ingredients.

      Where we disagree with you is here “Cholesterol as a target of food activists has been replaced by insulin. Saturated fat by carbohydrate. And the pendulum keeps swinging without moving a damn whit.” With all due respect, science progresses. Experimental techniques, including the ability to measure physiological processes, have advanced mightily since the heyday of the 4-part cholesterol test. The pendulum only exists in the media and in the random chook movements of individual opinion makers; awareness of insulin and indifference to saturated fat is scientific progress, especially if we consider the total health picture of which weight is only the most visible projection.

      The DIRECT results are what happens when you recommend LCHF to a group of people, many of whom really don’t want to hear it (it was recorded as the least popular option to be randomised to), at a time when it’s considered to be fringe science (which it wouldn’t be today). Nonetheless, if you look at reference 3, you’ll see a weight loss of 35% at 12 months and others in this ballpark. Statistically, these are more likely to be the Atkins dieters than low-fat low-calorie. It seems unlikely that someone who loses 35% of bodyweight on an ad lib diet without intense exercise will regain that weight on the diet. While water weight loss will account for a Kg or two in these extreme cases, overall carbohydrate intake in the Atkins group, even at 6 months, was too high to sustain water weight loss.

      The long-term data in reference 6 is also important as showing that higher-fat interventions do less harm over the long term than low-fat low-calorie interventions. The reason a doctor might recommend a diet may not be cosmetic; he or she may hope that the patient’s symptoms and risk of future illness will be decreased by weight loss. In this case, the DIRECT evidence shows that higher-fat interventions are more productive of benefit even when failure to lose weight or weight regain is taken into account, consistent with the results of weight-stable experiments such as reference 6.

      At a first approximation, and in our current food environment, LCHF diet advice is more helpful than other advice. The explanation John Yudkin gave in the 1960s still stands (quoted here https://profgrant.com/2016/05/09/lets-not-diet-like-its-1999-how-a-generation-of-nutritionists-and-dietitians-were-taught-to-make-weight-loss-more-difficult-than-it-needs-to-be/). It’s the best chance most people have to recapture control over the effect that the food environment is having on their health. As we move into an era where this is better understood and more socially acceptable, we’ll see better results than the DIRECT study did. But let’s not ignore the fact that people in that study succeeded in reaching their goals, and that randomisation to the LCHF diet maximised their chances of this. Randomisation to the Mediterranean diet also helped more people succeed than randomisation to the low-fat diet. Fear of fat seems to be the worst thing you can teach someone who is trying to lose weight.

  9. David Ludwig has just published an excellent Viewpoint article in the JAMA which briefly references Freedhoff and Hall and makes the same points we did.

    http://jama.jamanetwork.com/article.aspx?articleid=2564564

  10. Interesting discussion. Denise Minger recently brought up some historical information about very low fat/very high carb diets. Apparently the Kempner rice diet which had 95% of calories from carbs, including 2000 calories from refined sugars , led to massive weight loss, and even reversal of metabolic syndrome , diabetes, hypertension and cardiac failure. How can we reconcile this with what we now know about insulin resistance and the role of carbohydrates and refined sugars? Can very low fat AND very low carb diets both have the same effect ?This is from Minger https://rawfoodsos.com/2015/10/06/in-defense-of-low-fat-a-call-for-some-evolution-of-thought-part-1/#kempner and the original studies are linked there.

    1. I have a theory about how very low fat diets can reverse diabetes. They probably will only work in people with hyperinsulinaemia and insulin resistance, I wouldn’t expect good results if beta cells are failing.
      Let’s assume that everyone, including carb adapted people, has a minimum need for fat. Some cells (like heart muscle) can only work well on fatty acids and ketones. Fat is also structurally important. Let’s say this absolute need is 60-80 g/day. On a 30% fat diet you’ll get this, and if not you’ll make it up from DNL (fat synthesised from glucose), but if fat drops to 10% or less DNL will not be sufficient to make up the difference.
      The only way to get the needed fat is by upregulating lipolysis from stored fat, and this will include fat stored in liver and pancreas. Insulin sensitivity will improve because of this. Which in many ways is the SAME thing that happens on a keto diet.
      Of course the diet is not nutritious, and there are risks in the parameters of how well the sugar is tolerated at first, but in theory it can certainly work.

  11. Adherence is a function of the results a person gets. Low adherence to a diet is a symptom as much as it can be a cause.

    Let’s give people a diet that works for them and we won’t have to be worried about their adherence. Let’s continue giving people pseudoscientific diets, like the hypocaloric diets that Freedhoff and Hall promote, and 100% adherence won’t fix the method’s faults.

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