New Review Paper on Dietary Fat and Heart Disease Risk
A new review paper on dietary fatty acids and heart disease risk was just published by Dr. Rajiv Chowdhury and colleagues in the Annals of Internal Medicine-- one of the top medical journals (1). The goal of the paper is to comprehensively review the studies evaluating the effect of dietary fatty acids on heart (coronary) disease. The review covers observational and intervention studies pertaining to saturated, monounsaturated, trans, omega-6 polyunsaturated, and omega-3 polyunsaturated fats. The paper is notable for its comprehensiveness (inclusion criteria were very lax).
Here is a summary of the results:
In observational studies that measured diet, only trans fat was related to cardiovascular risk. Saturated, monounsaturated, and polyunsaturated fats were unrelated to risk.
In observational studies that measured circulating concentrations of fatty acids, long-chain polyunsaturated fatty acids (DHA, DPA, EPA, AA) were associated with lower risk. The dairy-fat-derived margaric acid (17:0) was also associated with lower risk. No other fatty acids were related to risk, including trans fatty acids.
In controlled trials, supplementation with omega-3 or omega-6 fatty acids did not alter risk.
The authors conclude:
In conclusion, the pattern of findings from this analysis did not yield clearly supportive evidence for current cardiovascular guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of saturated fats. Nutritional guidelines on fatty acids and cardiovascular guidelines may require reappraisal to reflect the current evidence.
Key limitations of this meta-analysis are that 1) it lumped together a variety of studies of different design and quality, and 2) it can only be as good as the studies it's based on. Meta-analyses are considered the highest level of evidence, but I remain somewhat skeptical of them for those reasons.
This paper contains something to upset just about everyone. Whether you believe saturated, monounsaturated, omega-6, omega-3, or even trans fat influences cardiovascular disease risk, this paper didn't consistently support any of it, instead suggesting that perhaps dietary fat composition isn't where we should be focusing our attention.
Does it challenge my own position? Perhaps a little bit, but not very much. After considering new evidence and reviewing old evidence, I've gradually drifted away from the view that omega-6 polyunsaturated fat contributes to cardiovascular disease. I still think it's probably a bad idea to eat a lot of refined seed oils-- the lipid equivalent of white sugar-- but I don't see much of an argument for avoiding whole nuts and avocados. Recent controlled trials and meta-analyses have also dampened my enthusiasm for the idea that omega-3 fatty acids have a major impact on cardiovascular disease risk. Either the trials weren't long enough to see protection, or omega-3 isn't as powerful as we had hoped.
The data on saturated fat are consistent with my long-standing position. If saturated fat consumption impacts cardiovascular disease risk, the effect must be small because it's difficult to detect. However, that doesn't mean it's prudent to eat a bacon and butter diet. These studies reflect typical dietary patterns and have nothing to say about extreme diets. Personally I'm wary of diets very high in saturated fat because we don't have much good quality data on them, and contrary to what is claimed in some circles, it probably does not resemble what our ancestors ate.
One of the associations that was identified in this meta-analysis is that circulating margaric acid is associated with lower cardiovascular risk. This is consistent with the findings of my review paper on full-fat dairy, suggesting that the consumption of full-fat dairy is associated with a lower risk of obesity and metabolic dysfunction (2). We don't know whether those results reflect cause and effect. However, we do know that there is little evidence to suggest that dairy fat is harmful to health.
Overall, this meta-analysis argues that dietary fat composition may not be a key factor in cardiovascular disease risk. That leaves us with these important but uncontroversial factors: genetics, overall diet quality, body composition, physical fitness, hypertension, and cigarette smoking.
"I still think it's probably a bad idea to eat a lot of refined seed oils-- the lipid equivalent of white sugar-- but I don't see much of an argument for avoiding whole nuts and avocados." I find it interesting, though, that the results didn't reveal any negative effects of PUFAs on cardiovascular health. Considering how much refined seed oils people tend to consume these days, one would expect to see some pattern in these results. I'm really confused, to be honest.
I notice that they did not include any dietary intervention with modified fat intakes (replacing SFA with PUFA or MUFA). A recent Cochrane review (Hooper et al. 2012) of interventions concluded that modification of fat intake
results in a significant 14% reduction in CHD incidence. The only RCT's in Chowdhury et al. are trials with supplements.
Which reminds me about a nice quote from Skeaff & Miller's 2009 metaanalysis: "... the evidence from cohort studies of dietary intake of fats and CHD is mostly unreliable (with a few exceptions) because most studies have ignored the effects of measurement error and regression dilution bias."
Do you think Matt Lalondes attempt (via nutrient density & other variables) is a good one?
I would define it as an omnivorous whole food dietary pattern including plenty of unrefined plant foods. Low in soda, junk foods like pizza, chips, cake, cookies, white flour, sugar, etc
Stephan: The Cochrane analysis excluded the Finnish Mental Hospital Study and any cluster randomised trials. But it was included in Skeaff & Miller (2009) and Mozaffarian et al. (2010).
The Cochrane meta-analysis included Oslo, even though they didn't considered it to be "free of systemic difference in care" and "free of dietary differences other than fat".
Generally speaking, the fat modification (SFA >> PUFA) trials also decreased trans fats and/or junk food in the experimental group
Many years ago I went to a talk by Richard Doll on cancer. In the question time he was asked about saturated fat, and said he never ate butter because it causes heart disease. His colleague Richard Peto had some data suggesting this. As it happened, a study had just been published in Science showing that dairy products protect against heart disease. I said so and he was not pleased. I talked to him afterwards, trying to mollify him, but it was no good. I was an enemy.
A few years ago I tried communicating with Richard Peto about heart disease, telling him about the association with copper deficiency. Somehow this association has escaped notice here in Oxford. I got nowhere, and concluded that Peto was just as frightened of Richard Doll as I was.
And, what about cancer?
The effect of fat, generally, and omega 6 polyunsaturated fat, in particular, on cancer has not been studies as extensively as its effects on CVD--but what evidence there is suggests cancer might be a real concern. Look at the Lyon Diet Heart study or the Veterans Trial. Look at the numerous animal studies.
I acknowledge that in recent years, new data cast doubt on the previously assumed mechanism for omega 6's potential adverse effects (i.e., it now appears very likely that the mechanism is not a result of too much AA leading to inflammation). That said, there are other plausible mechanisms, like epigenetic effects or oxidation/depletion of endogenous antioxidants.
Depending on the mechanism, you might be right that nuts or avocados are fine... On the other hand, it also seems there is little risk in keeping omega 6 consumption reasonably low, so why not limit nuts and avocados out of caution?
The two humans trials I mentioned:
Lyon: http://www.ncbi.nlm.nih.gov/pubmed/9625397
Veterans: 
Steven Hamley: Yes, the Oslo study (the first one, by Paul Leren) was meant as a "cholesterol-lowering" diet, not particularly a high PUFA-diet. The participants were encouraged to eat more fish etc., but in the end about 70 % of their fat intake came from soybean oil.
I'm wondering about the usefulness of measuring biomarkers of MUFA acid as a measure for intake. We convert oleic acid in vivo from desaturation of stearic acid, and it has been suggested that endogenously synthethized MUFAs have different effects from MUFAs from the diet.
Perhaps that is why the correlation coefficient between circulating and reported MUFA was only 0,05?
Reijo said...
Finnish Mental Hospital Study is included in this new meta-analysis also (see supplements). An interesting nuance is that the analysis of prospective cohorts showed null results for saturated fat in both cholesterol (lipid) adjusted and non-adjusted models. Siri-Tarino's meta-analysis was criticized because it adjusted for cholesterol. Now we know that non-adjusted analysis give the same results.
It's a pity that the authors did not run the substitution analyses for cohorts (SFA->PUFA) like in the pooled analysis by Jakobsen et al. 2009. I think it matters a lot what you have in place of sat fat.
Brian Scott Edwards MD said...
I look to new metrics of LDLp, CAC & CIMT to be used in diet trials. I have posted my results on LCHF diet without confounding co-variable of weight change. As a Lipidologist I question value of Good cholesterol vs. Bad cholesterol and large vs small particles.
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has the following:
"The Department of Health Dietary Reference Values remains the basis for UK dietary advice.[vii] It has not been updated in the past 22 years, despite epidemics of obesity and type 2 diabetes having developed in this time. This document recommends that “the population’s average intake of non-milk extrinsic sugars [free sugars] should not exceed about 60 g/day or 10 per cent of total dietary energy.” "
This is pretty close to the Kitavans' daily intake of CHO from fruit, allowing for differing average body mass.
(Thank you that series, way back when. I enjoyed it.)
Are you aware of Heisenbug who argues that underlying the cigarettes and fiber is a change to colonic bacterial ratios?
A practical question: I have been buying olive oil for most cooking, and even making mayo. It is more expensive that the other cooking oils, this study seems to indicate that I am wasting money??
Debbie PT said...
Thanks Stephen for this information. The nutritional guidelines and cardiovascular guidelines help me a lot, as always keep the healthy living. It is true that the key to it all is exercise even you eat a lot as long as you burn more calories!
Deborah Koval
Hi Stephan, can you please give your take on this very different opinion on the Chowdhury work?
http://plantpositive.squarespace.com/blog/
Apparently there was a lot of adjusting and fudging of numbers in order to get the results Dr. Chowdhury got.
RLL, really the study is saying that decisions should be based on more than just sweeping guidelines unleashed in the media. Olive oil has benefits when olive oil itself is compared to other oils, which wasn't the case in these studies.
Seppo, studies that purport to show that replacing SFA with PUFA reduces CDH risk are actually comparing people with low PUFA intakes (some of whom are probably EFA deficient) with people with high intakes. Essential fatty acids are essential, but adding amounts of linoleic acid high enough to lower serum cholesterol might be counter-productive as this increases cholesterol synthesis as well as uptake.
"although cholesterol synthesis increases with high PUFA intake, the lowering of plasma LDL-C observed with PUFAs is likely due to other mechanisms, including redistribution of cholesterol between plasma and tissue pools and upregulation of the LDL receptor. In contrast, the observed increases in plasma cholesterol concentrations due to SFAs do not appear to be related to a rise in cholesterol synthesis. However, when intake of TFAs [trans-fatty acids] was compared to palmitic acid, an increase in both cholesterol synthesis and plasma LDL-C concentrations was observed, suggesting that cholesterol synthesis contributed to the higher concentration of circulating LDL observed with TFA intake"
Mark Drangsholt said...
My friend Karl Kaiyala mentioned you today at lunch. I am an epidemiologist and oral medicine specialist at UW. I found out in June of last year that I was APOE4 carrier. It helped explained that even though I had a healthy lifestyle as a competitive triathlete and relatively low sat fat diet, my LDL was always elevated. I went on a low sat fat diet and my LDL became normal.
You may have seen the recent paper of a small RCT at the Seattle VA published in JAMA Neurology in August 2013 showing that people with mild cognitive impairment and healthy controls showed improvement in Alzheimers biomarkers like amyloid when they were fed a strict low sat fat, low glycemic index diet for 30 days. The effect in APOE4 carriers or homozygotes showed an even larger effect, which are people like me.
What this tells me is that the days of saying "I like this diet" or " That diet is good" are probably over. It depends upon your underlying genotype, and other factors, which diet may be optimal to prevent disease and maintain wellness for any particular person. This is just the start of this movement, in my opinion.
Mark Drangsholt
Thanks for your comment. I agree with your point. I think that's a profound limitation of most biomedical research: significance is based on sample averages and individual variability is often ignored.
I find it really interesting to look at the RCTs of this or that diet, and compare them to the anecdotes people report online. A number of people claim that a low-carb, higher-saturated fat diet generally improved their lipid profile, including reducing LDL. Others find that their LDL goes through the roof. If you look at the RCTs, LDL doesn't usually change much with that type of diet on average.
Same with body weight. Most overweight people lose body fat on a low-carb diet, while a few actually gain fat. On average, they lose fat, so that's what we hear about.
A lot of the variability must be genetic. APOE4 is one of the few alleles we've identified that seems to have a major effect on lipids. We still have a lot to learn. The big question is how do we predict who does best on which diet. Unfortunately the GWAS studies have mostly been disappointing in this department.
Hi again. As predicted by the Plant Positive blog post I sent you, there has now been published this article on the errors in Chowdhury's work:
I'd be interested in your take on all this.
Travis Culp said...
A few years ago I added a bunch of butter to my diet and it took my total cholesterol from 181 to 393. I then cut out butter altogether and it went right back down to where it was after ~6-8 months. That told me everything I needed to know about the subject. I suppose I may be an APOE4 carrier as well.
In any event, the odds of me simulating familial hypercholesterolemia via butter consumption and somehow sidestepping the health consequences of such a large LDL pool seemed highly unlikely. Keeping 200mg/dL from oxidizing seems doable, but 400?
Relying too much on the results of studies can be very dangerous. Although, when I looked into it afterward, I did find a study that found the fatty acid composition of butter (high myristate) to be a potent cholesterol-booster, with coconut oil being next in line.
Travis, 23andme confirmed me as APO E4/E4, and over the past 20 years, my total cholesterol has crept up from the 190s to the low 230s. My diet used to be heavily based on whole grains and beans, per new-age hippie vegetarian dogmas, and now it's moderate carb, highish fat with very little starch. My take on APOE4 is that it doesn't pigeonhole all carriers into a rigidly defined set of physiological patterns. For all the talk of APOE4 and lipids, the only thing that screws me over is excessive amounts of carbohydrate.
Tim said...
Given the poor quality and dubious intent of this meta-analysis I would hesitate to draw any definitive conclusion from it.
There have been significant errors pointed out (the use of _completely wrong_RR_, omission of major studies), leading to hasty corrections, but given the magnitude of the errors and the general lack of accuracy they suggest the calls for retraction are getting louder each day:
IMO, this paper is just another unfortunate example of the many shabby meta-analysis apparently designed to make big media headlines and grab the maximum amount of attention instead of advancing our understanding of a given subject (in fact, such studies often effectively spread confusion and distract the public from the real state of knowledge, which drives researchers like Willet, having done years of tedious work to expand that knowledge, understandably mad). Such papers should ring an alarm bell regarding today's standards of scientific publishing.
Mind you: Willet is the last one, you would suspect of being biased against dietary fat. In fact he always opposed the indiscriminate demonization of dietary fats even at a time when the overwhelming scientific consensus was against him. He was among the first to acknowledge the data rehabilitating full-fat dairy as heart-healthy and anti-obesogenic.
Sten Björsell said...
If the danger with pufas do not show up until after several years would not a number of studies have to be excluded. In my mind most of the natural fats we eat are well supplied with antioxidants, also added to many omega-6 oils. After 5 years consumption Chris MasterJohn pointed out that cancer started to increase in the n-6 group, in the "veterans study". Not before. If each gram n-6 require x mg antioxidants per day to not spoil in the body, 6 years high consumption of n-6 requires a daily intake of antiox twice that of 3 years to preserve existing n-6 in use and store in the body. Is this similar to the "empire effect" that made the fall of the Roman empire inevitable?
Is the effect of large pufa body stores similar in cancer and CVD?
Ivor Goodbody said...
"We DO know that there is little evidence to suggest that dairy fat is harmful to health."
To cardiovascular health, perhaps.
But I thought I should flag up the growing evidence of possible associations between even relatively moderate dairy fat intake and prostate cancer:
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Regulation of Food Intake, Energy Balance and Body Fat Mass: Implications for the Pathogenesis and Treatment of Obesity. J Clin Metab Endocrinol. 2012.
The Relationship Between High-fat Dairy Consumption and Obesity, Cardiovascular, and Metabolic Disease. European J Nutr. 2012.
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