Just Read: Saturated Fat in Meat is not associated with Cardiovascular Disease – How to make it look like it is

2018.05 Low Carb and Low Carbon - Ted Eytan MD-1001 1113

2018.05 Low Carb and Low Carbon – Ted Eytan MD-1001 1113 – (View on Flickr.com)

I’ve recently put out a solicitation for physicians to send me evidence that low carbohydrate or animal source foods are harmful for our health. This is a breakdown of one paper sent to me by a physician colleague purporting to show that there’s an association between saturated fat consumed in meat and cardiovascular disease, compared to dairy or plant sources of saturated fat (reference is at the bottom). The quick answer on this paper is – no evidence.

My method

I usually look at these aspects of any study I review

  • Is there conflict of interest on the part of the authors / study?
    • This includes financial as well as ideological
  • Is the methodology fit for purpose for the question being asked?
  • What are the results, and are they robust?
  • Is there newer/better research out there on this topic?

and

  • I read the whole paper
  • I grab the supplemental materials – often the real conclusions are stuffed there
  • I look up any tools used, including food frequency questionnaires

Let’s go….

Conflict of interest level – Off the charts

When the conflict of interest section is this large….

In this case the list is full of food companies and their proxies, all of whom have a significant financial interest in meat-alternatives. The authors are also notable for their promotion, in many other research articles, of polyunsaturated fats produced by these companies as health foods.

DM has received research grants from GlaxoSmithKline, Sigma Tau, Pronova, and the NIH for an investigator-initiated, not-for-profit clinical trial of fish-oil supplements and postsurgical complications; ad hoc travel reimbursement and/or honoraria for research presentations on diet and cardiometabolic diseases from the International Life Sciences Institute, Aramark, Unilever, SPRIM, and Nutrition Impact; ad hoc consulting fees from Foodminds and McKinsey Health Systems Institute; and royalties from UpToDate for an online chapter on fish oil. Harvard University has filed a provisional patent application that has been assigned to Harvard University and lists DM as a coinventor to the US Patent and Trademark Office for use of trans palmitoleic acid to prevent and treat insulin resistance, type 2 diabetes, and related conditions. DRJ is an unpaid member of the scientific advisory board of the California Walnut Commission. MCOO, JAN, DK, AGB, and CTS had no conflicts of interest to declare.Oliveira Otto, Marcia C de, Dariush Mozaffarian, Daan Kromhout, Alain G Bertoni, Christopher T Sibley, David R Jacobs, and Jennifer A Nettleton. “Dietary Intake of Saturated Fat by Food Source and Incident Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis.” The American Journal of Clinical Nutrition 96, no. 2 (August 1, 2012): 397–404. https://doi.org/10.3945/ajcn.112.037770.

For my physician colleagues who seem to be unaware of the portfolios of these organizations, I will elucidate, since it appears to be necessary.

  • International Life Sciences Institute (ILSI) – A food industry lobbying group founded by Coca-Cola (which has left the group as of 2021, however funded work like this). Here’s a helpful article by Belinda Fettke showing the connections to medical education.
  • Unilever – A prominent benefactor of researchers in this cohort. Here’s a view of their product portfolio. I should write a post just about this company and their product mix/financial interest. I didn’t understand it until a few years ago. I guarantee that most physicians don’t, either.

These 10 companies make a lot of the food we buy

These 10 companies make a lot of the food we buy – (View on Flickr.com)

The data/study that the analysis is based off of, the Multi-Ethnic Study of Atherosclerosis (MESA), is well respected. This piece was published very early in MESA’s origin, it’s number 479, in a publication list that is now 1846 items long. I scanned the list of publications and didn’t see an update to this particular analysis. However, I did see these, which would go against the conclusions of this paper.

  • Hu, Tian, David R. Jacobs, Lydia A. Bazzano, Alain G. Bertoni, and Lyn M. Steffen. “Low-Carbohydrate Diets and Prevalence, Incidence and Progression of Coronary Artery Calcium in the Multi-Ethnic Study of Atherosclerosis (MESA).” British Journal of Nutrition, January 11, 2019, 1–8. https://doi.org/10.1017/S0007114518003513.
  • Weir, Natalie L., Sarah O. Nomura, Brian T. Steffen, Weihua Guan, Amy B. Karger, Ronald Klein, Barbara E.K. Klein, Mary Frances Cotch, and Michael Y. Tsai. “Associations between Omega-6 Polyunsaturated Fatty Acids, Hyperinsulinemia and Incident Diabetes by Race/Ethnicity: The Multi-Ethnic Study of Atherosclerosis.” Clinical Nutrition 39, no. 10 (October 2020): 3031–41. https://doi.org/10.1016/j.clnu.2020.01.003.

Methodology – Food Frequency Questionnaire observational study

These types of analyses are best used for exploration rather than finding out if X causes Y, and suffer from a myriad of problems. This study is no different and is in fact among the worst I’ve seen, because of what study subjects were asked about their meat intake and how their answers were categorized.

Examples (from the supplemental materials)

  • What counted as “unprocessed meat”
    • Meat stew
    • Burritos with meat
    • Stir fried beef, pork or chicken
    • Pasta tomato sauce with meat
    • Hamburger
  • What counted as “mixed animal and plant”
    • Fried fish
    • Burritos (I guess the ones without meat?)
    • Pies
    • Fried chicken

The food frequency questionnaire is just as un-useful in terms of answering the study question. I encourage anyone to look at it. There are cultural-specific dishes, but no specificity – subjects are asked to recall how often they ate “stir-fried beef, pork or chicken with vegetables, including beef broccoli” in the last year. The last year….

Pasta tomato sauce with meat?
Stir-fry?

There’s no way to separate what meat derived saturated fat vs other fats and ingredients that are doing to harm health, like cooking oils, from this data.

Is this methodology fit for purpose? For exploration, yes, for any conclusions, absolutely not.

And as we’ll see the exploration didn’t point to meat as a health risk, either.

The results – not robust (at all)

Using statistical manipulation, the researchers attempted to separate the impact of saturated fat in meat on cardiovascular disease vs saturated fat in other foods.

First, we have to look at the people in each category of saturated fat intake. The subjects with the highest saturated fat intake were

  • More likely to be White
  • More likely to be overweight or obese
  • Less likely to be physically active
  • More likely to smoke
  • Less likely to drink

With the exception of alcohol use (which is always subject to recall bias), the people who ate more saturated fat (and also meat), are of the “unhealthy” phenotype. This means they are in general less likely to get preventive care, follow health guidance, and participate in other healthful activities that might prevent CVD. Researchers can adjust for some of these things, but not all. This is where healthy user bias creeps in. I’ve written a blog post with one example to explain what that is (see: Just Read: Healthy User Bias: Statin Adherence and Risk of Accidents) and there are many scholarly papers on this topic.

And then the results fall apart.

The “fully adjusted model,” which includes statistically removing the impact of

education level (less than high school, high school, or more than high school), active leisure (walking, sport, and conditioning in metabolic min/wk), sedentary leisure (television viewing, reading, and light sitting activities in metabolic min/wk), alcohol intake (ethanol g/d), smoking (never, former, or current smoker and number of pack-years of cigarette smoking), BMI (in kg/m2), dietary supplement use (at least weekly; yes or no), and cholesterol-lowering medication use (yes or no). intakes of fruit and vegetables (servings/d) and energy-adjusted intakes of dietary fiber (g/d), dietary vitamin E (IU/d), trans fat (g/d), and PUFA (g/d).Oliveira Otto, Marcia C de, Dariush Mozaffarian, Daan Kromhout, Alain G Bertoni, Christopher T Sibley, David R Jacobs, and Jennifer A Nettleton. “Dietary Intake of Saturated Fat by Food Source and Incident Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis.” The American Journal of Clinical Nutrition 96, no. 2 (August 1, 2012): 397–404. https://doi.org/10.3945/ajcn.112.037770.

..showed no significant association between meat-derived saturated fat and cardiovascular disease. What the authors report as the “significant” association is the not-as-fully adjusted model, which does NOT include adjustment for any of the items above. In other words, the researchers determined that less healthy people are less healthy.

There is some honesty in the chart used to describe the association, which I adapted in the graphic above. The chart shows that there’s NO association between meat derived saturated fat and CVD. Unfortunately, it’s produced in a sneaky way, which hides the fact that there’s no significance in the fully-adjusted model. When the confidence intervals cross 1.0 (no effect), the likelihood of an association could be based on random chance. This says nothing about causation, whatsoever. To make things worse, the actual data used to generate the chart are not available. This is obfuscation.

meat SF was not statistically significantly associated with risk [HR (95% CI) for extreme quintiles: 1.40 (0.94, 2.08); P-trend = 0.12]Oliveira Otto, Marcia C de, Dariush Mozaffarian, Daan Kromhout, Alain G Bertoni, Christopher T Sibley, David R Jacobs, and Jennifer A Nettleton. “Dietary Intake of Saturated Fat by Food Source and Incident Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis.” The American Journal of Clinical Nutrition 96, no. 2 (August 1, 2012): 397–404. https://doi.org/10.3945/ajcn.112.037770.

In other words, I call this a case of covering the tracks of a non-significant finding, so ultimately, it’s dishonest.

Is there newer, better research out there?

This paper is now 9 years old. It uses one of the least robust methodologies there is in nutrition research. Surprisingly, it has recently been discussed on social media – perhaps this paper has been circulated more recently, which is why it was sent to me.

In any event, there are much better analyses available looking at impact of saturated fat and meat intake on health

  1. JACC State of the Art Review on Saturated Fat – See: Saturated fat does not clog the arteries, increase CVD risk or increase diabetes risk. The end.
  2. NUTRIrecs series – See: Most important part of this week’s published nutritional guideline recommendations – personal preferences and values are respected
  3. The PURE study – See: Just Read: More Validation of Low(er) Carb High(er) Fat Diets: The PURE Study and Lipids
  4. (from the MESA study) Hu, Tian, David R. Jacobs, Lydia A. Bazzano, Alain G. Bertoni, and Lyn M. Steffen. “Low-Carbohydrate Diets and Prevalence, Incidence and Progression of Coronary Artery Calcium in the Multi-Ethnic Study of Atherosclerosis (MESA).” British Journal of Nutrition, January 11, 2019, 1–8. https://doi.org/10.1017/S0007114518003513.
  5. (from the MESA study) Weir, Natalie L., Sarah O. Nomura, Brian T. Steffen, Weihua Guan, Amy B. Karger, Ronald Klein, Barbara E.K. Klein, Mary Frances Cotch, and Michael Y. Tsai. “Associations between Omega-6 Polyunsaturated Fatty Acids, Hyperinsulinemia and Incident Diabetes by Race/Ethnicity: The Multi-Ethnic Study of Atherosclerosis.” Clinical Nutrition 39, no. 10 (October 2020): 3031–41. https://doi.org/10.1016/j.clnu.2020.01.003.

Here’s another review

My conclusion – try again

For all of the reasons above, this paper fails the test of usefulness in guiding health decisions. On to the next!

Reference

Oliveira Otto, Marcia C de, Dariush Mozaffarian, Daan Kromhout, Alain G Bertoni, Christopher T Sibley, David R Jacobs, and Jennifer A Nettleton. “Dietary Intake of Saturated Fat by Food Source and Incident Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis.” The American Journal of Clinical Nutrition 96, no. 2 (August 1, 2012): 397–404. https://doi.org/10.3945/ajcn.112.037770.

My disclosures

I have none, including that I am not an advocate or activist for any specific dietary pattern. I am an advocate for the desire to know what’s accurate when it comes to dietary patterns. My disclosures page is available here.

6 Comments

So you cherry picked the funding of some industries but ignored funding of beef checkoff program? National dairy council? National egg board?

Why?

Ahoy and thanks for stopping by!

I quoted word for word the conflicts of interest from the article. Did you see something in the article that I didn’t? Have a great day, Ted

… I’ll take your non-response as agreement that the post is accurate. Agree that conflict of interest is a major problem, and definitely one in this paper.

Glad this is useful and may help your audience be better information consumers! Sadly this is tip of the iceberg (lettuce), Ted

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Ted Eytan, MD
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