Lessons from Diet RCTs II: Randomizing, Blinding, and perhaps even Controlling, is Futile

You hear it all the time -- the randomized controlled trial is the "gold standard" for clinical research.  Unfortunately, just because something is an RCT doesn't make it a good study, not by a long shot.  I blogged recently calling for an end to diet comparison RCTs because I don't believe this model is productive in identifying what a healthful non-obesigenic diet is for humans.  All of the foods that have been blamed have been around for far longer than this problem has, so, frankly it really isn't the food.  There's no magical macronutrient ratio, no superfoods that will impart you with superhuman powers, and no foods that are inherently fattening or slimming ... even butter and celery, but please no buttered celery.

I really do believe that observational studies have far more value than clinical trials in this realm.  I'm not talking about the ones taking two hours of self-reported intake and massaging the data for obscure correlations to demonize some dietary factor.  No, I'm talking about long term observations of traditional cultures.   It seems that every culture ate different foods and they were all relatively free from chronic diseases associated with the "First World".  Pretty much every demonized food (not talking chips, dips and nips or scones and cones) is prevalent in some culture that is healthy despite(?) its consumption.

As Gary Taubes rightly (yes it happens!) points out in his recent NYT article, short term trials are never going to answer the question of what happens in the long term.  Further, let's face it, there will no more be one perfect human diet agreed upon, than there will ever be consensus on the paleo diet.

When I lost a good chunk of weight using very low carb several years back, I felt pretty good (though frustrated with the plateauing out).  Several years prior, I had experienced some disconcerting side effects following a similar diet including racing heart, and basically feeling "skiddly" and "not right" sometimes with even mild exertion or none at all.  So since I wasn't losing more weight, I went looking for reassurances that how I was eating was healthy for the long term.  This is where I've gotten in trouble for my honest assessment of the only "evidence" there is out there:  the advocates who claim to have been following a VLC diet for years and decades even.   But there really isn't much more to go by.   The essentially starch and sugar free diet with relatively high domestic animal fat and dairy fat does not emulate any, and I do mean any, traditional culture's diet.

The even "long term" diet comparison studies are essentially useless, and this  latest one pitting "paleo" vs. "low fat" was no exception.  In a nutshell, the diets as implemented differed considerably from as described, and there is a lot of ambiguity as to the adherence to "the diets" themselves.  This is nothing new.  Other studies such as Dansinger, Foster, Shai, and many more have all suffered the same problems.  Low fat not really being low fat, reported calorie intakes not squaring with weight regain, veggie oils as margarine, etc.  When celebrity followers of various diets die unexpectedly, and especially when the diet gurus themselves die of undisclosed causes, it makes for a rather scary landscape out there.   We are inundated with before and after testimonials of amazing success in all things and boundless energy, only when you read the personal posts of these same people they tell a different story.  They report questionable health markers (to put it mildly) yet claim to have the answers to healthy living.  It is all a bit too much.  Rather than these contests in the guise of science, I'd rather see what 30 motivated people who will adhere (as much as can be expected) to their diet for several years and be verifiably monitored for health markers and incidence of disease, etc.

Randomized Controlled Trials

RCT's have their place.  They are truly a gold standard for things like pharmaceutical research or limited dietary interventions.  For example, let's use a hypothetical pain killer study involving aspirin, acetaminophen, ibuprofen and naproxen.  One might be interested in comparing the effectiveness for a certain kind of pain (let's say post surgery) where the subjects will rank pain levels on some sort of scale before and at some time after taking the medication.   So

So first, some definitions and explanations.  I've probably blogged on this stuff in parts elsewhere, but heck, it's easier to just rattle it off again.   RCT stands for Randomized Controlled Trial.  Before we discuss the "R" and the "C", let's talk experiments and confounding variables.

Experiment:  An experiment involves applying some "treatment" and measuring/assessing the effect of the treatment on some variable or variables.  There is a designated primary outcome, in our pain relief study this would be reduction in some pain score, but there may be secondary outcomes as well, perhaps mood changes or cognition.   Experiments differ from Observational Studies in that those only involve collecting data with no active intervention.

Confounding Variable or Confounder:   In the context of an experiment, a confounder would be some factor or variable other than the "treatment" that might be responsible for the observed effects.    If a new heart drug is tested and an increase is seen in heart attacks, if there were a lot of smokers in the group, this might be a confounding variable.  The smoking, and not the drug, could explain the results.   Technically speaking, any factor can be a confounder, but usually when we use the term we mean the more likely ones.

Pre-Screening & Confounders:  In most studies, the subects are narrowed down to a relatively homogenous group to avoid some obvious issues such as medications, complications of unrelated medical conditions, smoking, weight status, thyroid issues, age, etc.  This helps cut down on the possible "silent confounders", but it also narrows the population for which inferences can be drawn from the results.

Controlled:   Control in the context of an experiment refers to holding as many possible confounding variables constant between two or more groups so that ideally the only thing that differs between groups is the treatment.  In our pain killer hypothetical, this is rather easy as the treatments can be easily standardized to the same number of the same sized pills or capsules, and if the study is done in a post surgery recovery room, the environment can be kept quite consistent.   The constancy of possible confounders should not be confused with compliance control.  It is unfortunate that control is such a general word that can be confused with control over implementation of the experimental protocol.  This is an entirely different type of control, discussed this in more depth here:  A Matter of Control.  I'm also not a big fan of describing a study as "uncontrolled" (see:  http://scholar.google.com/scholar?q=uncontrolled+study), if only because it seems to imply useless chaos.  Later in this post, I'll make the case for where such "lack of control" in the experimental sense may not be such a big deal after all, especially if "control" in the compliance sense is more stringent.

Randomizing:  This indicates that the subjects are randomly assigned to at least one treatment group and one control group.  In my pain killer hypothetical, these drugs have all been available OTC for quite some time, and some are advertised quite aggressively for superior pain relief.  Therefore potential subjects may have a preferred drug and/or perception of the efficacy of these drugs.  We wouldn't want subjects self-selecting their treatment.   Random assignment to a group serves to "average out" potential confounders, even those that may not be considered to be important.  I would say that height is likely not a factor in pain killer efficacy, but you never know.  Rather than taking any chance on the investigator assigning taller people to one treatment on some subconscious level, if subjects are randomly assigned, the height of the groups should ... well ... "average out" to be roughly equal.   With smaller sample sizes, "pure" randomizing may not be the best assurance of equal distribution, something that I've pointed out when discussing some studies where baseline characteristics differ between groups.

Blinding:  Blinding refers to knowledge on the part of the subject and/or investigators as to the treatment each subject receives.  In single blind, the subjects do not know which treatment they receive, in double blind neither subjects nor investigators know.   The former is sufficient in cases where objective measures are involved.   For example, a cholesterol lowering drug where cholesterol is measured.  Cholesterol levels are what they are, there's no "I think" or "I feel" involved.  If you have a subjective measure, double blinding is essentially required and failure to do so renders results suspect.  Since pain is a subjective measure (see here for example), the potential for bias on the part of the patient and the person administering the test is high.  

The Hypothetical Pain Killer RCT

Recruit potential subjects at a clinic that does minor surgery.  OK ... let's say bunions.  Crap ... I just checked ... that can be more painful than I thought.  Run with me on this one and let's presume this is a routine outpatient deal.  I could prescreen patients at a clinic for eligibility according to pre-surgical medical records (however to work that with access, etc.), excluding those with known circulation issues, smokers, and those with diabetic neuropathy to name a few.  Might exclude those on medications entirely or at least those whose medication schedule would be altered for surgery.     This pool would then be offered free surgery in exchange for participation.  Within ethical guidelines they would know in advance that they would experience some post-op pain at baseline and again the experts could dither on what level of pain/duration they would be allowed to opt out at.   This probably selects a more pain-tolerant group, but they will all be so predisposed.

So we'd have 4 study groups receiving different meds and a control group receiving a placebo pill.  Let's say, 40 subjects in each group.  Assignment would be random.  The surgery would be performed, and some fixed time afterwards when the local had worn off, the subjects' baseline pain would be evaluated.  After which they would receive treatment and monitored for pain levels every two hours for the next 12.  This would occur in a recovery room where the subject had a comfy recliner and access to a ton of entertainment or could bring stuff from home.  Assistance using the bathroom, meals provided and all that jazz.   The dose/frequency would be established for each drug for "standard care" (e.g. if one is long acting or the other short) and placebo pills would be added to other regimes so that all subjects took identical appearing pills on the same schedule.  A system of "packs" could be worked out so the person assessing pain could also administer the meds "blinded".  

This is a pretty perfect type of experiment for the blinded RCT.  Pretty easy, with a little creativity, to standardize things such that all other factors are "averaged" out of the equation and we just measure the effects of the drugs themselves.  It's done all the time.  It's a great model ... one might even say "gold standard".  It can accommodate a few challenges.

Limitations for the Nutritional RCT

Let's cut to the chase and then backtrack here.  The RCT model is of very limited usefulness in the context of nutrition.  Food is not a pill, or an injection.  Varying diet is not like 100 minutes in a dark room with The Ramones vs. Miley Cyrus blaring nonstop.   There are too many other variables that get in the way most of the time.  

A successful RCT with meaningful results would require a metabolic ward setting.  In addition, at the very least we're talking Nutrisystem style meal delivery with some attempt to match the tastes, textures and visual appeal of the meals between diets.  This is rather impossible if we're talking Atkins induction vs. Ma Pi.   In terms of diets per se, it seems relatively futile to randomize people to different extremes as you are dooming some to failure no matter what.  So what if either of the aforementioned diets can lead to miraculous results if it's not a realistic plan for a person to sustain for the long term.

The RCT seems a more effective model for shorter term evaluation of particular dietary components.  So, for example, the type of fat can be easily manipulated by using shakes, muffins or even working it in as supplement capsules.  Ditto protein or sugars or different carbohydrate sources.  Even drastic variations in macros can be accommodated by using shakes.   The results of these studies are of limited value translated to any general population in free-living conditions, however.  They are good for teasing out the sort-of quality vs. quantity questions.

The Paleo vs. Nordic Nutrition Recs Single-blind RCT

After baseline measurements, the women were randomized to a PD or a Nordic Nutrition Recommendations (NNR) diet for 24 months.  
All study personnel (except the dieticians) were blinded to the dietary allocation of the participants.
Both diets were consumed ad libitum.
Each group took part in a total of 12 group sessions held by a trained study dietician (one dietician per diet) throughout the 24-month study period. The group sessions consisted of information on and cooking of the intervention diets, dietary effects on health, behavioral changes and group discussions. The subjects were given recipes and written instructions to facilitate the preparation of meals at home. Eight group sessions (four cooking classes and four follow-up sessions) were held during the first 6 months of the intervention.  Additional group meetings were held at 9, 12, 18 and 24 months.
 As a result here was the compliance ...

values in ( ) are negative

I believe this study is a perfect example of the futility of trying to fit dietary research into the blinded RCT model just for the sake of it. 

Blinding - What's the Point?   Think about this. You sign up for a study. You will be prescribed some diet to follow for two years. Do you think that in a free living situation where you are selecting and preparing your own foods you won't eventually realize what diet you're following? Nevermind if you're the least bit curious ... In the end, how can you blind a diet? Unless you were to feed these people Nutrisystem style 24/7/365 it seems ludicrous to even bother.

Randomizing - Good Idea if it's a Competition! I remember listening to an interview with Dr. Dansinger who did the first dietary RCT. It was a novel idea and he discussed the challenges of randomizing people to different diets. The problem with all of those studies is that they were set up more as contests than anything else. Which one produced more weight loss, which one lowered LDL the most, which one improved blood sugar best, etc. You'd think by the third one or so these researchers might catch on. Over and over (and over and over) again, tucked in the discussion somewhere, the following seems to always hold: adherence is the best predictor of success. The diet is irrelevant, and for most, losing a degree of excess weight precipitates the rest of the health improvements. When someone wants to lose weight or improve health (or both) in real life, they choose their way. It's still dang hard to enact changes, most will rapidly abandon what's not working and gravitate towards what they are most motivated to sustain. I think we would get more actionable information from these sorts of trials if we don't set things up as a competition and allow participants to self-select their diet. Who cares what unquantifiable biases this may throw into the mix -- there are all manner of those inherent in the process anyway. If someone chooses the diet there is a greater chance they'll adhere to the program and stick with it for the duration of the study ... in other words, provide any sort of meaningful information to the rest of us!

Control? Sure, if it's a Contest!   Speaking of self-selecting, why are we having these diet contest RCT's? If the low sat fat, high fruit, moderate carb, high protein diet used in these paleo studies produced dramatically better results in 10 trials, would this change anything? No. Most will not find a dairy, grain and legume free existence sustainable. Nor would the majority prefer 150g protein per 2000 calories. Ditto the spartan use of salt, dressing, etc. I would much rather see 20 dedicated ketogenic dieters submit to thorough health monitoring for a period of years to see what effect it has on biomarkers and metabolism than another study like this. But it would be uncontrolled!! So what, I say! We actually have proxy controls which would be the baseline anthropometrics for subjects and the general population. This is the important stuff. Does the Atkins diet cause improvements or worsening of risk factors with time. How about if I went raw vegan? What can I expect if I commit to such a lifestyle? Wouldn't we all much prefer that 100 vegans register for such a study where instead of anecdotes on the internet we can never confirm shared by people with a financial interest to their entire livelihood wrapped up in advocating a particular diet. 

Moving Forward ...

A year ago today, a NuSI-funded study got underway involving 600 people.   I'm not sure the intervention part has yet started.  Subjects were or will be  randomized to one of two "extreme" diets: 
Extremely low-fat diet
Diet reduces fat intake as much as possible (below 10%), with as much carbohydrate and protein intake as desired and highly processed grains and sugars discouraged.
Extremely low-carbohydrate diet
Diet reduces carbohydrate intake as much as possible (below 10%), with as much fat and protein intake as desired and highly processed grains and sugars discouraged.

The lead researcher is Dr. Gardner of Stanford who conducted one of the famous diet comparison studies:  The A to Z Study.  This one is popular in LC circles because, "A" stands for Atkins, and Atkins "won" the race.  

Image not available.

We learned:
Although adherence to the 4 sets of dietary guidelines varied within each treatment group and waned over time, especially for the Atkins and Ornish diets, we believe that the adherence levels obtained are a fair representation of studying the diets and variations in macronutrient intake under realistic conditions and, therefore, increase the external validity of the findings.
Ornish is supposed to be very low fat, and yet at 2 months participants were consuming over 20% fat and this increased to about 30% by 1 yr.  The Atkins dieters, meanwhile, dipped below 20% carb at 2 months, but were up over 30% by study end.
Mean 12-month weight change was −4.7 kg ... for Atkins, −1.6 kg ... for Zone, −2.2 kg ... for LEARN, and −2.6 kg ... for Ornish and was significantly different for Atkins vs Zone.
To translate, the Atkins dieters had a net **statistically INsignificant** loss of 2.1 kg (< 5 lbs) more vs. Ornish at the one year mark.  But you know, those studies haven't been done yet to give us the answers.    According to NuSI, their new study is ...
... designed to test two very different dietary interventions in free-living subjects to elucidate the role of fat and carbohydrates on body fat and chronic disease risk factors. It expands on work by Gardner et al. reported in JAMA in 2007 – “Comparison of the Atkins, Zone, Ornish, and LEARN Diets for Change in Weight and Related Risk Factors Among Overweight Premenopausal Women” (commonly referred to as the “A TO Z” study). In this previous study, which compared four diets varying in macronutrient content, Gardner et al. reported that consumption of fat and carbohydrates converged over time toward a single common diet similar to the subjects’ pre-study diets.
By the end of the year-long study, only the subjects assigned the two diets most divergent in fat and carbohydrate (the Atkins diet and the Ornish diet) differed substantially in their intake of these macronutrients. The difference between these two groups in the A TO Z study remains one of the best examples of dietary differentiation in a free-living study, and the A TO Z study is currently the most read study on nutrition in JAMA.
So.   The problem with A-to-Z was what?  The prescribed diets weren't extreme enough?   It doesn't appear so, though perhaps not to Gary Taubes' tastes.  No, the problem was -- especially in the most extreme cases of Atkins & Ornish -- even sticking to those.

I wonder what the budget on this thing is.  I wonder what better uses those dollars could have gone to.   In 2016, when this study gets published up, will we have more answers than we do today?  Very highly doubtful.


If my weight change after a year of VLC or VLF was less than 10 lbs, I'd be wondering why I bothered! Ah compliance ;). That said, the most interesting thing to me from Gardner's original study was his subsequent look at individual participants' responses to the different diets based on their insulin sensitivity (and after that, their DNA). I wonder whether he'll be looking at this in this go-round? It's not exactly like that revolutionized the weight-loss world.
LWC said…
I agree that adherence is the bottom line for any diet. A VLC or VLF diet isn’t ever going to appeal to me, even if one is better than the other for weight loss because an extreme diet is not required for weight loss.

However, VLF (Ornish and Esselstyn for example) have been shown in clinical trials to reverse heart disease. I know some people dismiss the Ornish intervention because it involved factors other than diet, but in a recent radio “debate” with Chris Masterjohn, Dr Michael Greger also pointed to the VLF diet clinical study done by Esselstyn that also reversed heart disease. Masterjohn tried to dismiss the results because they weren’t achieved in an RCT, but fact of the reversal couldn’t be denied.

I think I would adhere to an extreme diet if it reversed disease. So far, the only option to reverse heart disease is VLF, and with adherence it works.

If NuSi recreated Ornish or Esselstyn’s clinical results with VLC, that would be groundbreaking.
Wuchtamsel said…
Yes, looking at weight loss studies one could come to believe it was actually impossible to lose more than ~10 pounds in/for a lifetime...
carbsane said…
If NuSi recreated Ornish or Esselstyn’s clinical results with VLC, that would be groundbreaking.

If (big IF) they don't do an intent-to-treat analysis on just high adherence completers, this would likely be the unintended outcome/consequence.

I agree with you -- If motivated, an extreme diet becomes more sustainable. In some ways, it can be a curse to "get away" with a bad diet for too long!

I didn't get a chance to catch the debate. Busy times.
carbsane said…
They say they are going to look at all sorts of things. There might be some info to be gleaned there, but unless there's better compliance than to the less stringent initial intervention (unlikely!) it won't give much to really work with.
LWC said…

I don't understand what you mean here.
ZM said…
Esselstyn’s plan also involves cutting out junk foods together with increases in fruit and vegetable intake, and using cholesterol lowering drugs such as statins. Is it really surprising that his subjects improved when they adopted a better diet than their previous one? We are also talking about surrogate markers here so I don't see what all the fuss is about. I agree with Masterjohn - http://www.westonaprice.org/thumbs-down-reviews/prevent-reverse-heart-disease
eulerandothers said…
Can I attempt to understand this? If they don't do an intent-to-treat analysis on just high adherence completers.... If they include everyone, including the people who dropped out without being able to finish, then they limit results to the short-term. There are no shortage of studies that offer short-term results (showing results that vary all over the place, from study to study). The need to show that something happens beyond the short-term - with high adherence 'completers' makes a difference.
eulerandothers said…
There's a National Weight Loss Registry that keeps records of people who have kept off weight they lose. It shows how they do it, too - weight loss maintainers do share some habits or techniques. These people have to volunteer to share their information with the Registry and as I remember it, they have to get their doctors involved with verifying the information. People do lose weight and keep it off.
carbsane said…
Ugh I worded that awkwardly. In so many of these studies they do the intent to treat analysis and include all subjects whether they completed or not. In the good ones, the publish a "completer analysis" as well.

I can understand ITT from a physician POV. They can't know every detail about their patient, so if someone has high BP, then the drug that lowers BP the most for the highest percentage of people is the better "first line" treatment. But even as a physician, I would want to know what the best possible outcome is.

Antibiotics should be taken for the full course to fully eradicate infection. It's like saying penicillin is ineffective because the 20% who stop taking it after 4 days see their infections return.

So what I was saying is that if they look at just the long term adherents, I think they will see better improvements on the VLF than VLC. If they don't look to tease out some level of adherence to compare (out of 300 you should hopefully at least have 30 that do adhere strictly in each group) and show that analysis, I'd say that hints at trying to cover up.
LWC said…
Okay, I see what you both mean. But I'm curious as to why there isn't any clinical trials using the VLC to show reversal of heart disease. I mean, cardiologists have written LC diet books... why haven't any cardiac surgeons repeated the clinical studies only with people eating VLC?
LWC said…
But here's my question: where are the clinical trials in which people with heart disease are put on a VLC diet (or a WAPF diet) and then shown by direct measurement to reduce the plague in their arteries?
ZM said…
The thing is that Esselstyn or Ornish never showed their diet to be superior to VLC or WAPF because those diets were not comparison groups in their studies. If you are only going by diets that have already been tested why not go with those which have already been shown in randomized controlled trials to reduce clinical events instead of possibly meaningless surrogate outcomes?
charles grashow said…

"The rate of adherence to a study diet was 95.4% at 1 year and 84.6% at 2 years. The Mediterranean-diet group consumed the largest amounts of dietary fiber and had the highest ratio of monounsaturated to saturated fat (P<0.05 for all comparisons among treatment groups). The low-carbohydrate group consumed the smallest amount of carbohydrates and the largest amounts of fat, protein, and cholesterol and had the
highest percentage of participants with detectable urinary ketones (P<0.05 for all comparisons among treatment groups). The mean weight loss was 2.9 kg for the low-fat group, 4.4 kg for the Mediterranean-diet group, and 4.7 kg for the low-carbohydrate group (P<0.001 for the interaction between diet group and time); among the 272 participants who
completed the intervention, the mean weight losses were 3.3 kg, 4.6 kg,and 5.5 kg, respectively."

" after 6 years, people in the low carb group regained 4.1kg, people in the low fat group regained 2.7kg, and people in the Mediterranean group had regained only 1.4kg."
LWC said…
They weren't comparing diets though, as I understand it, they were trying to reverse heart disease (by decreasing the clogging of the arteries and eliminating cardiac events) using the diet they thought most likely to do so.

Why haven't cardiac surgeons who believe in VLC (or WAPF if that's your cuppa) done the same?

Cardiologists have written LC diet books... why haven't any clinical trials been done where heart disease patients follow a VLC diet and have periodic angiograms to measure the plague progression in their arteries?

I don't care if other (such as VLF) diets ALSO work... if VLC works to reverse heart disease, why it hasn't been shown , or no effort has been made to show it. The more options people have to reverse heart disease the better, I would think.

Let a thousand flowers bloom....
JC Carter said…
So RCTs have issues, so you want to instead use observational trials that have far more issues? Sure you put the disclaimer on "not the ones with two hours... etc" but how would you measure long term data in traditional diets (especially as most cultures are no longer anywhere near their traditional diet", and following this, how will they measure associations between these diets and any proposed health outcome outside of correlating one factor to another factor, resulting in either negative or positive claims around said factor.
carbsane said…
Yeah, this was kinda my point. Take some people with plaque, put them on your diet, see if it works. Uncontrolled. Yeah. But you're right, I don't recall it being done.
ZM said…
LWC: "Why haven't cardiac surgeons who believe in VLC (or WAPF if that's your cuppa) done the same?"

I don't know! I'm not the person to ask since I do not follow these diets or their gurus. Nevertheless, I really don't see the point in these surrogate marker studies which may not translate into anything meaningful.
carbsane said…
There can be no absolute certainties, but we know with pretty good certainty how Americans ate in the 50's, in the 1900's, and a few hundred years before that. We know from studies of various cultures and even from traditional recipes, etc. handed down from generation to generation how humans have eaten.

And all of them eventually got old and died, they didn't look like they did at 30 until they croaked, etc.

Prospective studies can tell us a lot ... perhaps not about causality, but these RCTs tell us a lot less in that regard.
JC Carter said…
We know what people ate if we like averages, or vague generalisations... but little about distribution, variation, and extremely little about health. Traditional diets are not fixed entities, and varied with whatever the local environment threw at them. We have enough trouble figuring out dairy consumption, which is a relatively simple consumption, compared too the alternatives.

We know more about what they wouldn't have eaten, than what we know about what they ate.

And all of them did not get old, just as all of modern humans, with all out medical intervention, get old and die.

Prospective studies are the best of a bad bunch. Most have provided erroneous information that have driven large quantities of pointless RCTs, vague public health recommendations, wasting dollars and costing lives.

Taking the hard edge on the RCTs you have presented, the final outcome is that nutrition research should be dumped. It is obviously too difficult to research an area that requires behaviour change, in a society that cannot change their nutritional behaviour. Combined with the alternative, statistical masterbation of large poorly measured untrustworthy datasets.
Or we can hope that what the average of what our "ancestors" ate will be suitable, environmentally sound, and suitable for our genetically diverse modern population. I have ancestry from scandinavia, through normandy, across england and scotland, into ireland, and from there across USA and somewhere some polynesian. What diet do i eat?
Wuchtamsel said…
As a matter of fact RCT with an "intention to treat" design don't work at all with dietary modifications because compliance is essentailly nonexistant...
Wuchtamsel said…
These patients in the Ornish and Esselstyn "studies" (They are a scientific joke for more than one reason...) were NOT treated with diet alone but also with the dreaded statins, although Esselstyn doesn't get tired to claim the doses were "very small". On the other hand I've never seen the doses published anywhere so...
carbsane said…
Perhaps I should re-write or append. There is more to science than observational study vs. RCT. Indeed we know a lot from uncontrolled metabolic ward studies on a handful of subects at a time. We also learn a lot from the "case study" which is seemingly a thing of the past in the peer review. Would be interesting to have some sort of registration for these. But using the NuSI study, I'd rather they recruited 100 folks each to follow either diet in the dormitory setting that another NuSI study is being conducted and do it for a few years. There's the problem. Length of the RCT. This is where those pesky observations of traditional diets come in. I'm NOT talking paleo or even 1000 years ago. I'm talking 100-200 even.

My point about studies on traditional diets is that humans can thrive on a variety. I'm afraid that in your and my lifetimes they won't have the genetics worked out to what we should eat. But these RCT's offer us little to no further information. How can they since nobody seemed to comply with either diet or stick to it very well after a few months?
Wuchtamsel said…
"Indeed we know a lot from uncontrolled metabolic ward studies on a handful of subects at a time."

Actually we know MOST what we really know from those kind of studies. That's worth to think about. From an EBM-based view it's for example almost impossible to improve cholester values by diet interventions. There actually are textbooks that claim exactly that without a tongue in cheek base on flawed RCTs... From the kind of ward studies you described we know it's possible and (almost) everybody who is motivated enough can reproduce these results.
charles grashow said…

Each participant also received an individualized prescription for a cholesterol-lowering drug. The most frequent regimen included cholestyramine, 4 g twice daily, and lovastarin, 40 mg to 60 mg daily. Time-release niacin was prescribed for a short while but was discontinued when many patients reported nausea, vomiting, and swollen ankles.
The length of the study is totally the problem. Two years of VLC may be great if you can do it (seemingly most study participants can't), but what about 20? Or 40? The heck with hunter-gatherers, consider Dan Buettner's Blue Zones. Note that there's more than diet that goes into their longevity (hint: they don't spend a lot of time agonizing over what to eat!).
carbsane said…
That book is on my reading list. Thanks for making my point better than I articulated it re: time frame.
I think Ragen Chastain has some good points about the usefulness (or not) of the NWLR.
eulerandothers said…
I will look more closely at that blog entry from Chastain and also at the NWLR. But first things first:

The name of the researcher is Rena Wing (not Wring)., Wing RR if you do a search in NCBI.

I don't know about Miriam Hospital, but she is on the faculty of Brown University Medical School



Chastain says, ' To sum up, it was started by people who make
their money researching, discussing, and selling weight loss.'

Just looking at Wing, it seems she has other sources of income. But, aside from that, it lumps her in the category of anyone who blogs or flogs with a sales pitch on the Internet (paging Dr. Mercola - he's a real doctor!) so already, Chastain's lost ground with me.


According to this interview,

Dr. Rena Wing: I have a registry of individuals who have lost weight successfully. On average, they have lost more than 60 pounds and kept it off more than 6 years. They report eating a low-calorie, low-fat diet with less than 24% of calories from fat. They all eat breakfast regularly! This is interesting because many dieters try to skip breakfast. The successful weight losers also do a lot of physical activity, almost an hour a day.

All this is too, too boring: Ho hum. Eat less, move more.

Low-carbers, when I mentioned this registry on a low-carb board had problems with its very existence. It requires the cooperation of your doctor - what do doctors know? I don't need no stinkin' doctor. They're all part of the medical-Big Pharma complex that conspires to keep us all fat!

So, there's a problem there. Low-carbers are less likely to even volunteer their data, from the reaction I got. However, the Registry itself is not one big controlled experiment. They are a 'prospective investigation'; I'm sure those words were chosen carefully.


'The National Weight Control Registry (NWCR), established in 1994 by Rena Wing, Ph.D. from Brown Medical School, and James O. Hill, Ph.D.from the University of Colorado, is the largest prospective investigation of long-term successful weight loss maintenance. Given the prevailing belief that few individuals succeed at long-term weight loss, the NWCR was developed to identify and investigate the characteristics of individuals who have succeeded at long-term weight loss.'

Look to the individual studies produced to critique their methods and conclusions.


'Weight-loss maintenance for 10 years in the National Weight Control Registry.'
LWC said…
I'm not against pharmaceuticals either. If I develop heart disease, I want as many treatment options as possible.
Wuchtamsel said…
Sure, but that's not the point. It's impossible to tell which role the diet played in these (very badly designed) trials.
eulerandothers said…
So the one area shared by these three groups contains:
family, no smoking, plant-based diet, constant moderate physical activity, social engagement and legumes. Got it.
ZM said…
I'm fully aware of the "oxidative response to inflammation hypothesis" and have read that paper before. I'm not sure what point you are trying to make though.
Lighthouse Keeper said…
Add a stress relief technique to that inner shaded area and you have something very much like the Ornish programme requirements.
eulerandothers said…
No particular point, except I discovered Roland Stocker - and for that, it was worth reading the Masterjohn.

'It is not revolutionary because advocates of vegetarianism, and opponents of dietary fat have been stretching science for ages.'

And yeah, I get the point that Masterjohn doesn't like vegetarians. And he's got something he'd like you to buy in his references!
Kevin Klatt said…
Great read, and lots of good discussion in the comments area. I think my biggest issue with RCTs is that they miss nutrient synergy/interactions. just focusing on, say, saturated fat and heart disease, and using RCTs that vary the amounts of SFAs can't determine the relative protective roles of fiber, vitamin E/C/K, omega 3's, etc.
MacSmiley said…
Esselstyn did have one patient who went completely drugless, a colleague at the Cleveland Clinic who was not a candidate for surgery and who wanted nothing to do with the side effects of statins.

The A/B comparison of the man's angiogram is startlingly impressive.

Figure 1 shown at


-- Coronary angiograms of the distal left anterior descending artery before and after 2 months of a plant-based diet without cholesterol-lowering medication, showing profound improvement
MacSmiley said…
When I see visible proof à la Esselstyn of patients following Masterjohn's recommendations at 5 year intervals, published in JAMA or the like, I'll consider following his advice.

In the meantime, eating mostly plants is the way I'll go. Loving my lipid panel.

PS. Dr. Greger's grandmother was one of Pritikin's early success stories. Masterjohn will never convince Greger because of his eyewitness experience. His wheelchair-bound grandmother, who'd run out of blood vessels for any further bypasses, walked out of Pritikin's center after a few weeks and lived a healthy life for several mor decades.
MacSmiley said…
Esselstyn and Ornish showed more than surrogate markers. They presented angiograms of cleared arteries that had formerly been blocked with atheromas.
ZM said…
Changes seen on angiogram are surrogates. Let me know when both Ornish and Esselstyn conduct a properly controlled study comparing their diets to others they are fond of criticizing, on actual clinical events. Until then, there is no reason to adopt their extreme diets.
carbsane said…
I am not advocating anyone's diet here, like to make that clear up front. Also, I have no idea what the verification process is/was for any of these results. BUT -- if one shows reversal of plaque with a diet, that is not a surrogate, that is a physical manifestation. In this regard, this would be the type of "uncontrolled" experiment that would be more beneficial to others in choosing their dietary path. The VLC people could do their own study with their diet in a similarly verifiable fashion. As it stands, from the LC camp we get statements from Davis that his patient's Ca scores are similar but they're not getting heart attacks anymore. How do we know this?
eulerandothers said…
Pritikin insisted that an autopsy be done on himself after he died. The results were published in the New England Journal of Medicine.


In contrast, when Robert Atkins died, from a fall, he had the heart health of 'man his age' (he was in his 60s). All of which proves exactly nothing. However,

The race is not always to the swift, nor the battle to the strong, but that's the way to bet.

-Damon Runyon
ZM said…
I wouldn't accept such data from any camp. Reversal of plaque is a surrogate endpoint, not a cardiac event. Coronary angiography is limited in measuring plaque anyway, which was used in these studies.