25 replies to this topic

[kismet]

Did I miss the discussion of this study?

BACKGROUND:

Observational cohort studies and a secondary prevention trial have shown an inverse association between adherence to the Mediterranean diet and cardiovascular risk. We conducted a randomized trial of this diet pattern for the primary prevention of cardiovascular events.

METHODS:

In a multicenter trial in Spain, we randomly assigned participants who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly individual and group educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was the rate of major cardiovascular events (myocardial infarction, stroke, or death from cardiovascular causes). On the basis of the results of an interim analysis, the trial was stopped after a median follow-up of 4.8 years.

RESULTS:

A total of 7447 persons were enrolled (age range, 55 to 80 years); 57% were women. The two Mediterranean-diet groups had good adherence to the intervention, according to self-reported intake and biomarker analyses. A primary end-point event occurred in 288 participants. The multivariable-adjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.54 to 0.92) and 0.72 (95% CI, 0.54 to 0.96) for the group assigned to a Mediterranean diet with extra-virgin olive oil (96 events) and the group assigned to a Mediterranean diet with nuts (83 events), respectively, versus the control group (109 events). No diet-related adverse effects were reported.

CONCLUSIONS:

Among persons at high cardiovascular risk, a Mediterranean diet supplemented with extra-virgin olive oil or nuts reduced the incidence of major cardiovascular events. (Funded by the Spanish government's Instituto de Salud Carlos III and others; Controlled-Trials.com number, ISRCTN35739639.).

(1) Estruch R, Ros E, Salas-Salvadó J, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med 2013; DOI: 10.1056/NEJMoa200303.
http://www.nejm.org/...6/NEJMoa1200303

I am working on a Question & Answer section for my blog. You can ask me anything, but please provide concise questions if you would like me to write an explanation.

[Jakare]

Mixed nuts is a bit vague. Any chance of knowing what nuts where included in the mix? Hopefully they weren't salted.

Nice study.

Edited by Jakare, 16 May 2013 - 12:12 PM.

[kismet]

30 g/d of raw & unsalted nuts (15 g walnuts, 7.5 g hazelnuts, and 7.5g almonds) were provided.

Edited by kismet, 19 May 2013 - 08:01 PM.

[Chupo]

Only the olive oil decreased all-cause mortality.

[helluva nootro]

Very interesting, thanks for your posts

just a quick Q, what is the benefits of Extra virgin or virgin olive oil over your standard? Its a question I can find the answers to with a quick search but some of the longecity members like to hyper-analyse and can give better answers, thanks again

[kismet]

Finally, finished.

I am going to discuss the failings of the PREDIMED study, real and imagined. I will do this in a Question & Answer style. Several questions are inspired by theheart.org and NEJM comments and even statements by the low fat "gurus", Essselstyn, Ornish, McDougall or Pritikin. It is no surprise they are up in arms after the study has been published. It threatens their livelihood.

Finally, I get to talk about biogerontology, diet and health in one post. For once, I may be doing justice to the blog name. I will also talk about study ethics, particularly the balance of harms and benefits you may expose participants to. In jargon: clinical equipoise.

First, a summary of the study and its results:

http://biogerontolgy...edimed-and.html

[FunkOdyssey]

I've found it odd how excited everyone gets about the very modest effect of the mediterranean diet on the incidence and progression of heart disease, when a whole food, plant-based, oil-free diet has been shown to completely arrest and even reverse it. Maybe because it seems easier and less extreme?

[TheFountain]

I've found it odd how excited everyone gets about the very modest effect of the mediterranean diet on the incidence and progression of heart disease, when a whole food, plant-based, oil-free diet has been shown to completely arrest and even reverse it. Maybe because it seems easier and less extreme?

Are you suggesting a bias?

[Dolph]

I've found it odd how excited everyone gets about the very modest effect of the mediterranean diet on the incidence and progression of heart disease, when a whole food, plant-based, oil-free diet has been shown to completely arrest and even reverse it in roughly a dozen subjects receiving statins and other drugs.

FYP

[Michael]

I've found it odd how excited everyone gets about the very modest effect of the mediterranean diet on the incidence and progression of heart disease, when a whole food, plant-based, oil-free diet has been shown to completely arrest and even reverse it. Maybe because it seems easier and less extreme?

A whole food, plant-based, oil-free diet has never been shown to completely arrest and even reverse heart disease. To anticipate: I expect you're going to point to reports from Ornish and from Esselstyn, but Esselstyn's nor Ornish's reports are credible support for this claim. Both of their reports are in very small numbers of intensely-managed patients with existing CVD; neither of them have reported any actual improvement in survivorship; and there are major confounders for both. Esselstyn is reporting a case series from his personal practice, and not (as is often claimed) a clinical trial; there was no control group, and moreover ALL of his subjects were on cholesterol-lowering drugs.(1) Ornish's study is not an RCT, involved 20 active-group subjects, and was not a test of diet but of a complete lifestyle change (and are therefore not demonstrably related to the diet per se, let alone demonstrably better than a diet higher in quality fat): his intervention not only included low saturated fat intake (which is of course achievable with a diet high in mono- and polyunsaturated fats (like my 40% fat, 9% SaFa diet)), but also a "vegetarian diet, aerobic exercise, stress management training, smoking cessation, group psychosocial support" (2), none of which were administered to the controls.

By contrast, this was a real RCT, involved hundreds of subjects, only changed diet (and, when you dig into it, changed little other than EVOO intake), and actually showed a reduction in major cardiovascular events and a pretty clear EVOO-specific trend for mortality. (If you haven't read it, anyone with any of the standard objections raised in the press against PREDIMED should go and read kismet's excellent analysis).

As to actually arresting and reversing atherosclerosis: it's a surprisingly underreported fact that a real RCT of diet alone actually did show a reversal of atherosclerosis as measured by carotid vessel wall volume and IMT. The diet was not Ornish: it was Atkins.(3) To be fair, they found that all three diets studied (Atkins, Mediterranean, and modest low-fat) reduced carotid vessel wall volume and IMT; however, the Atkins diet led to nominally greater regression on carotid vessel wall volume (−84.33 mm3) than the other two (−37.69 and −60.69 mm3, respectively; P=0.28). And again, there is no such evidence for the kind of diet used in Ornish's study.

I am not endorsing Atkins -- I think one can do much better with a low-SaFA diet, and with less meat and other changes, and don't believe ketosis as such is important for health (of course, Atkins does not have to mean permanent ketosis)) -- but there's now real evidence of benefit there, and there is no such evidence for an ultra-low-fat Ornish/Pritikin/MacDougall/Esselstyn-style regimen.

References
1. Esselstyn CB Jr
Updating a 12-year experience with arrest and reversal therapy for coronary heart disease (an overdue requiem for palliative cardiology). Am J Cardiol. 1999 Aug 1;84(3):339-41, A8. PMID: 10496449 [PubMed - indexed for MEDLINE]

2. Ornish D, Scherwitz LW, Billings JH, Brown SE, Gould KL, Merritt TA, Sparler S, Armstrong WT, Ports TA, Kirkeeide RL, Hogeboom C, Brand RJ.
Intensive lifestyle changes for reversal of coronary heart disease. JAMA. 1998 Dec 16;280(23):2001-7. Erratum in: JAMA 1999 Apr 21;281(15):1380. PMID: 9863851 [PubMed - indexed for MEDLINE]

3. Shai I, Spence JD, Schwarzfuchs D, Henkin Y, Parraga G, Rudich A, Fenster A, Mallett C, Liel-Cohen N, Tirosh A, Bolotin A, Thiery J, Fiedler GM, Blüher M, Stumvoll M, Stampfer MJ; DIRECT Group. Dietary intervention to reverse carotid atherosclerosis. Circulation. 2010 Mar 16;121(10):1200-8. doi: 10.1161/CIRCULATIONAHA.109.879254. Epub 2010 Mar 1. PubMed PMID: 20194883.

Edited by Michael, 13 October 2013 - 04:46 PM.

[misterE]

I've found it odd how excited everyone gets about the very modest effect of the mediterranean diet on the incidence and progression of heart disease, when a whole food, plant-based, oil-free diet has been shown to completely arrest and even reverse it. Maybe because it seems easier and less extreme?

BINGO!

A whole food, plant-based, oil-free diet has never been shown to completely arrest and even reverse heart disease.

Then why is former president Bill Clinton using this approach to reverse his heart-disease? Do you think he is making a mistake?

http://www.youtube.com/watch?v=R3ied_AD4iE

Edited by Michael, 04 November 2013 - 12:06 PM.

[Michael]

I've found it odd how excited everyone gets about the very modest effect of the mediterranean diet on the incidence and progression of heart disease, when a whole food, plant-based, oil-free diet has been shown to completely arrest and even reverse it. Maybe because it seems easier and less extreme?

BINGO!

Yeah: I am really, really swayed by making sure that my diet be easy and not extreme .

A whole food, plant-based, oil-free diet has never been shown to completely arrest and even reverse heart disease.

Then why is former president Bill Clinton using this approach to reverse his heart-disease?

Because he's been convinced by poor arguments. The man is a politician, not a specialist in evidence-based medicine.

Do you think he is making a mistake?

I don't think he's making the best choice. I certainly think his current diet is better than his previous regimen of hamburgers, chicken enchiladas, barbecue and french fries, and doughnuts by the boxfull. But I don't think it's the best diet by a long shot, and "A whole food, plant-based, oil-free diet has never been shown to completely arrest and even reverse heart disease."

[misterE]

"A whole food, plant-based, oil-free diet has never been shown to completely arrest and even reverse heart disease."

Pictures don’t lie Mike:


Prev Cardiol. 2001 Autumn;4(4):171-177.

Resolving the Coronary Artery Disease Epidemic Through Plant-Based Nutrition.

Esselstyn CB Jr.

Abstract

The world's advanced countries have easy access to plentiful high-fat food; ironically, it is this rich diet that produces atherosclerosis. In the world's poorer nations, many people subsist on a primarily plant-based diet, which is far healthier, especially in terms of heart disease. To treat coronary heart disease, a century of scientific investigation has produced a device-driven, risk factor-oriented strategy. Nevertheless, many patients treated with this approach experience progressive disability and death. This strategy is a rear-guard defensive one. In contrast, compelling data from nutritional studies, population surveys, and interventional studies support the effectiveness of a plant-based diet and aggressive lipid lowering to arrest, prevent, and selectively reverse heart disease. In essence, this is an offensive strategy. The single biggest step toward adopting this strategy would be to have United States dietary guidelines support a plant-based diet. An expert committee purged of industrial and political influence is required to assure that science is the basis for dietary recommendations.

Edited by misterE, 24 November 2013 - 03:58 AM.

[Michael]

"A whole food, plant-based, oil-free diet has never been shown to completely arrest and even reverse heart disease."

Pictures don’t lie Mike:

Pictures don't lie, but anecdotes don't prove. See my comments above about Esselstyn.

(BTW, there is no "Mike" in this conversation — thanks).

Edited by Michael, 24 November 2013 - 01:41 PM.

[sthira]

Pictures don’t lie Mike

Pictures don't lie, but anecdotes don't prove. See my comments above about Esselstyn.

Hiya Michael! And of course sometimes pictures do lie. I'm not suggesting fraud in your posted pix -- far from it -- but sometimes we see what we want to see. And obviously sometimes we see what others desire that we must see.

[AstralStorm]

While I wouldn't agree about low fat being conducive to heallth, there are quite a few epidemiological and dietary intervention studies (yeah yeah, hard to make a control for plants for blinding) recommending a plant-based diet... Mediterranean is not exactly fully plant-based though. It contains an important amount of meat and fish.

I wouldn't go as far as to ascribing CHD-reversing effects to that alone though. The olive oil and other omega-3 rich fats (canola, flax) remain confounders in those studies as well.

Edited by AstralStorm, 01 December 2013 - 06:24 AM.

[misterE]

I think that the main benefits of the Mediterranean-diet is the fact that it is nearly vegetarian (lots of whole-grains, beans and vegetables); the diet is much lower in saturated-fat and higher in monounsaturated-fat which doesn’t paralyze insulin like the saturated-fats do.

But an Asian-diet is even better in terms of obesity and disease-rates. That is: people living around the Mediterranean are heavier and have more cardiovascular-disease than the Asian countries living on their traditional starch (rice) based diets. The Traditional Asian diet is 10% fat whereas the Mediterranean-diet is more around 30%.

The people who have the best longevity ever are the Okinawans who eat 90% complex-carbohydrate.

[timar]

"A whole food, plant-based, oil-free diet has never been shown to completely arrest and even reverse heart disease."

Pictures don’t lie Mike:

This is probably the single most naive statement I have seen in this forum so far...

The people who have the best longevity ever are the Okinawans who eat 90% complex-carbohydrate.

Could you vegans and wannabe hunter-gatherers please all stop to constantly misuse the Okinawan diet for justifying your dietary ideology? Yes, the Okinawan diet is a low-fat, high complex-corbohydrate diet. Yet the Willcox' write in their book The Okinawa Way that small amounts of pork and most of all fish are integral parts of the traditional Okinawan diet.

Edited by timar, 03 December 2013 - 10:33 PM.

[misterE]

Its naïve to ignore the implications of those pictures.

[timar]

Its naïve to ignore the implications of those pictures.

You mean the implications of selectively chosen pictures illustrating a non-randomized, non-controlled interventional study conducted by a single, highly biased practitioner, comprising an inextricable bundle of various lifestyle interventions? Well, for me the implications are that the strict standards of scientific evidence have been established for a good reason...

[misterE]

YAWN.

Edited by misterE, 03 December 2013 - 11:56 PM.

[Brett Black]

According to Peter Attia, M.D.:

"326 people would need to undergo this dietary intervention for about 4 or 5 years to prevent one “count” of the primary outcome."

http://eatingacademy...g-heart-disease

If this is correct, I'm very unimpressed.

[Michael]

While I wouldn't agree about low fat being conducive to heallth, there are quite a few epidemiological and dietary intervention studies (yeah yeah, hard to make a control for plants for blinding) recommending a plant-based diet... Mediterranean is not exactly fully plant-based though. It contains an important amount of meat and fish.

I think that everyone in this thread (except possibly Timar?) favors a plant-based diet. But a plant-based diet is not a vegan diet, let alone an ultra-low-fat diet, which is what Esselstyn preaches and to which Mister E has evidently become beguiled.

I wouldn't go as far as to ascribing CHD-reversing effects to that alone though. The olive oil and other omega-3 rich fats (canola, flax) remain confounders in those studies as well.

It's quite clear even from the epidemiology that the olive oil is one of the main drivers, not confounders, of the Med diet; IAC, the oils used in PREDIMED and the Lyon Diet Heart Study were not confounders, but the intervention itself.

I think that the main benefits of the Mediterranean-diet is the fact that it is nearly vegetarian (lots of whole-grains, beans and vegetables); the diet is much lower in saturated-fat and higher in monounsaturated-fat which doesn’t paralyze insulin like the saturated-fats do.

Esselstyn, of course, does not support high-mono, low-sat-fat diets, but pushes his patients to cut fat across the board. IAC, the results of PREDIMED can't be attributed to reduced saturated fat intake, because saturated fat intake was no lower in the olive oil or nut groups than in the controls.

But an Asian-diet is even better in terms of obesity and disease-rates. That is: people living around the Mediterranean are heavier and have more cardiovascular-disease than the Asian countries living on their traditional starch (rice) based diets. The Traditional Asian diet is 10% fat whereas the Mediterranean-diet is more around 30%.

Cross-cultural comparisons are not evidence.

The people who have the best longevity ever are the Okinawans who eat 90% complex-carbohydrate.

Er, those Okinawans are on CR . Of course, there are many more people in China and India eating 90% complex-carbohydrate diets, and their longevity is unexceptional. Cross-cultural comparisons are not evidence.

Could you vegans and wannabe hunter-gatherers please all stop to constantly misuse the Okinawan diet for justifying your dietary ideology? Yes, the Okinawan diet is a low-fat, high complex-corbohydrate diet. Yet the Willcox' write in their book The Okinawa Way that small amounts of pork and most of all fish are integral parts of the traditional Okinawan diet.

Integral, yes — for ceremonial reasons. Absolute intake of all animal flesh was much lower amongst today's Oki centenarians than average North American intakes, or even contemporary Japanese intakes. The same is true of traditional Cretan diets, whence the whole "Med diet" concept arose.

According to Peter Attia, M.D.:

"326 people would need to undergo this dietary intervention for about 4 or 5 years to prevent one "count" of the primary outcome."

http://eatingacademy...g-heart-disease

If this is correct, I'm very unimpressed.

The NNT was high because teh total event rate was very low. All subjects were agressively treated for cardiovascular risk factors; the effects of olive oil or nuts had to manifest in a context in which the controls (and active groups') cholesterol, hypertension, glycemia, etc were already substantially under control. The investigators had assumed an event rate of 11% over 6 years; instead, they got a 4% event rate over 5 years, and the ethical committee shut the trial down early — precisely because the relative reduction in risk was so substantial.

[timar]

I think that everyone in this thread (except possibly Timar?) favors a plant-based diet. But a plant-based diet is not a vegan diet, let alone an ultra-low-fat diet, which is what Esselstyn preaches and to which Mister E has evidently become beguiled.

I do, too. It's just that I always feel inclined to take a somewhat critical position when there is a consensus on a subject, at least when that consensus doesn't entirely rely on evident facts but on some kind of paradigm. That's why I mention the benefits of animal products when I'm discussing with vegans and their dangers when I'm discussing with paleo folks. I don't want to subscribe to any ideology when it comes to nutrition. And I like to disturb other people's opinion if it is all too complacent.

I wouldn't go as far as to ascribing CHD-reversing effects to that alone though. The olive oil and other omega-3 rich fats (canola, flax) remain confounders in those studies as well.

It's quite clear even from the epidemiology that the olive oil is one of the main drivers, not confounders, of the Med diet; IAC, the oils used in PREDIMED and the Lyon Diet Heart Study were not confounders, but the intervention itself.

Yep. It's mind-boggling how many people rush to downplay this study's findings without even having understood its design...

What's so remarkable about PERIMED is that, as a large-scale RCT, it served to fill a gap in the spectrum of evidence. We now have a complete picture, with consistent evidence from all fields of nutritional science that nut and oilve oil consumption are indeed remarkably health-promoting - and we can even relatively precisely quantify their effects.

That's probably why Vince Giuliano and James P. Watson went nuts too!

Er, those Okinawans are on CR . Of course, there are many more people in China and India eating 90% complex-carbohydrate diets, and their longevity is unexceptional. Cross-cultural comparisons are not evidence.

They can provide valuable evidence though, but only if combined with other categories of evidence from intercultural epidemiological studies, RCTs and lab work. For many essential components of the Okinawan diet, we have strong evidence of potent health-promoting effects. This gives us reason to assume that is is not only the "hara hachi bu" and other aspects of lifestyle but the qualitative composition of their diet as well which is of importance for the Okinawans' longevity.

Could you vegans and wannabe hunter-gatherers please all stop to constantly misuse the Okinawan diet for justifying your dietary ideology? Yes, the Okinawan diet is a low-fat, high complex-corbohydrate diet. Yet the Willcox' write in their book The Okinawa Way that small amounts of pork and most of all fish are integral parts of the traditional Okinawan diet.

Integral, yes — for ceremonial reasons. Absolute intake of all animal flesh was much lower amongst today's Oki centenarians than average North American intakes, or even contemporary Japanese intakes. The same is true of traditional Cretan diets, whence the whole "Med diet" concept arose.

Sure! Contrary to some paleo crackpots I would never claim that pork has been a quantitatively important part of the traditional Okinawan diet (in fact, I had just argued strongly against such prevarications). Fish and eggs, however, certainly were.

Edited by timar, 11 December 2013 - 05:20 PM.

[Brett Black]

According to Peter Attia, M.D.:

"326 people would need to undergo this dietary intervention for about 4 or 5 years to prevent one "count" of the primary outcome."

http://eatingacademy...g-heart-disease

If this is correct, I'm very unimpressed.

The NNT was high because teh total event rate was very low. All subjects were agressively treated for cardiovascular risk factors; the effects of olive oil or nuts had to manifest in a context in which the controls (and active groups') cholesterol, hypertension, glycemia, etc were already substantially under control.

Table 2 shows, across all groups, hypertension at ~80%, diabetes ~50%, dyslipidemia ~70%, BMI ~ 30, waist circumference ~100cm [1.] That doesn't look like cardiovascular risk factors are "substantially under control." Am I missing something? They were heavily medicated for these conditions, if that's what you mean...?

The investigators had assumed an event rate of 11% over 6 years; instead, they got a 4% event rate over 5 years, and the ethical committee shut the trial down early — precisely because the relative reduction in risk was so substantial.

According to Peter Attia leaving us with "no statistically significant difference in death (CVD or otherwise) or MI across the three groups."[2]


REFERENCE
1. Primary prevention of cardiovascular disease with a Mediterranean diet.
Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F, Gómez-Gracia E, Ruiz-Gutiérrez V, Fiol M, Lapetra J, Lamuela-Raventos RM, Serra-Majem L, Pintó X, Basora J, Muñoz MA, Sorlí JV, Martínez JA, Martínez-González MA; PREDIMED Study Investigators.
http://www.ncbi.nlm....bmed/23432189/?

2. "Is a Mediterranean diet best for preventing heart disease?", Blog - The Eating Academy, Peter Attia, M.D. http://eatingacademy...g-heart-disease

Edited by Brett Black, 12 December 2013 - 12:58 AM.

[kismet]

Brett,
I am >90% sure, not totally, but quite sure that the NNT is 5 times lower. I believe the calculator this Peter Attia used gives a NNT / year, which he confused with a NNR for the whole study. I arrive at the same number for a per-year-NNT as he did. Please correct me if I am wrong.

To quote myself from my blog where I already addressed most of your criticisms:

“Taking into account the small differences in the accrual of person-years among the three groups, the respective rates of the primary end point were 8.1, 8.0, and 11.2 per 1000 person-years” (crude rates)
1000 people need to be treated for a year to prevent 3 major events. [or one person for thousand years, so to say] That is a NNT of 333/year or 66 over 5 years. That is a respectable number given that the Mediterranean diet has no (known) side-effects and may be cost-neutral (i.e. free) if it replaces the regular diet.

Here, as a comparison 5-year NNTs for a few common drugs:
“5-year NNT values previously reported in primary prevention for the use of statins among hyperlipidemic men (5-year NNT, 40 to 70 [multiply with 5 to get one year NNT]), for antihypertensive therapy (5-year NNT, 80 to 160), or for aspirin (5-year NNT, >300)”
http://intl-circoutc...nt/2/6/616.full

EDIT: My bad. Looking at table 3 in the PREDIMED paper, actual sample size and event rates, I think that a NNT close to 300 over the whole study duration may be correct after all. That still seems acceptable.

According to Peter Attia leaving us with "no statistically significant difference in death (CVD or otherwise) or MI across the three groups."[2]
REDIMED Study Investigators.
http://www.ncbi.nlm....bmed/23432189/?

Neither was the rate of alien abductions reduced significantly. However, note that the study was not powered to detect changes in mortality (or alien abductions for that matter) Unless there is a plausible reason why the primary (composite) endpoint is not to be trusted, and why a reduced stroke rate is not supposed to translate into a mortality benefit, I would prefer to focus on something that study was capable of showing.

The study was "by design" incapable* of answering questions regarding mortality. It did not answer in the negative. Quite to the contrary, the study strongly suggests that olive oil can reduce total mortality. There is a plausible reason to mistrust the data on nuts and mortality, however...

Sure, I think this was a bad design choice, idiotic, to be quite honest. Sure, mortality is an even more powerful endpoint, but let's not forget that stroke/MI-composites are also incredibly strong endpoints.

*mathematically unlikely to answer

Edited by kismet, 19 December 2013 - 12:37 AM.