Saturated Fat and CAD: It's Complicated

Shifting Views on Saturated Fat

Dietary guidelines for the prevention or treatment of coronary artery disease (CAD) have emphasized a reduction in the consumption of saturated fat since the 1960s.^[1] Dietary saturated fat increases blood levels of low-density lipoprotein cholesterol (LDL-C) and subsequent risk for CAD, or so goes the conventional wisdom. Indeed, there are studies showing such associations,^[2,3] but other data challenge the hypothesis, including meta-analyses showing no link between saturated fat consumption and risk for CAD or cardiovascular disease (CVD).^[4,5] The disparate findings have led to calls to stop demonizing saturated fat^[6,7] and equally vocal cries to proceed with caution before we let lard back on the menu.^[8] Meanwhile, the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines on lifestyle management to reduce CVD risk omitted a target for total dietary fat but did recommend a goal of 5%-6% of calories from saturated fat.^[9]

Asking whether saturated fat is good or bad for your cardiovascular (CV) health is looking for a simplistic answer to a complicated issue. Saturated fat is not a single entity, and the merits of saturated fatty acids (SFAs) can depend on what you are comparing them with, what foods the fats are in, what dietary pattern these foods are part of, and who is doing the consuming. (Genetics and lifestyle influence the effect of diet on health.)

Saturated Fats and Lipid Levels

The different SFAs vary in their effects on lipid levels; of note, stearic acid is generally excluded from the listings of cholesterol-raising saturated fats.^[10,11] However, this thinking is the result of flawed logic, according to Dariush Mozaffarian, dean of the Friedman School of Nutrition Science and Policy at Tufts University in Boston, Massachusetts. "The US view on saturated fats is totally based on the effects on LDL-C, and that's why we have dietary guidelines to lower our saturated fat intake and why stearic acid is given a free pass," he noted in an interview with Medscape. SFAs are biologically complicated. "They don’t just affect LDL-C, they affect particle size, they affect HDL-C and triglycerides. It's not clear which [ones] are better or worse if you look at all of those effects."

In a meta-analysis of over 60 trials, higher intakes of saturated fat were associated with increases in both LDL-C and high-density lipoprotein cholesterol (HDL-C) and decreases in triglyceride levels, for a net neutral effect on the ratio of total cholesterol to HDL cholesterol.^[11] Although saturated fats increase LDL-C, they reduce the LDL particle number. Total LDL particle number quantifies the concentration of LDL particles in various lipid subfractions and is considered a stronger indicator of CV risk than traditional lipoprotein measures.^[12] As for stearic acid, the allegedly non-cholesterol-raising fat, while it appears to lower LDL-C relative to other SFAs, one analysis concluded that it raised LDL-C, lowered HDL-C, and increased the ratio of total to HDL cholesterol in comparison with unsaturated fatty acids.^[13] And this is one of the confounders of much nutrition research—observations about a given nutrient are highly dependent on what you compare it to.

As Marion Nestle, professor of nutrition, food studies, and public health at New York University in New York City, told Medscape via email, "Saturated fat raises LDL-C in comparison to the effects of unsaturated or polyunsaturated fatty acids...all food fats, without exception, are mixtures of the three kinds of fatty acids, so it is not surprising that the effects of foods and diets differ."

Focusing on Foods: Is Dairy Different?

Does it matter which foods the saturated fats come from? There is increasing evidence that dairy fats do not increase CVD risk and may even lead to a better metabolic profile. The MESA study asked more than 5000 adults aged 45-89 years to complete a 120-item food-frequency questionnaire and followed them for 10 years.^[14] A higher intake of dairy SFA was associated with lower CVD risk, whereas a higher intake of meat SFA was associated with greater CVD risk.

To explore the findings further, the MESA investigators measured baseline plasma phospholipid levels in more than 2500 participants. Plasma levels of the odd-chain SFA 15:0 (pentadecanoic acid) were inversely associated with incident CVD and CAD, while no association was found with the even-chain SFA 14:0 (myristic acid).^[15] Self-reported whole-fat dairy and butter consumption had the strongest associations with levels of 15:0. Dairy intake also correlates with a lower risk for type 2 diabetes: The EPIC-InterAct investigators looked at plasma phospholipids in a large prospective case-cohort study and saw an inverse association between odd-chain SFAs and type 2 diabetes (the analysis included over 12,000 type 2 diabetes cases).^[16]

Dr Mozaffarian observes that "we can't synthesize the odd-chain SFAs (15:0 and 17:0), so they're not in your blood unless you're eating dairy fat."

What You Replace the Saturated Fat With Counts

Cutting back on dietary fat typically means increasing consumption of other macronutrients. The spectacular failure of the Women's Health Initiative (WHI) Dietary Modification Trial,^[17] which showed no reduction in coronary heart disease or stroke in the almost 20,000 postmenopausal women assigned to a low-fat diet, was a blow to the dietary fat/heart proponents. The saturated fat target for the WHI intervention group was 7% of calories; participants got down to 8% of calories by year 1 (from about 13%) but bounced back up to 9.5% of calories by year 6. The clue to the failure of the intervention may be in what they were eating instead.

A pooled analysis of 11 prospective studies by Jakobsen and colleagues^[18] that included more than 340,000 healthy adults older than 35 years suggests that consuming polyunsaturated fats instead of saturated fat lowers the risk for CAD whereas replacing the saturated fat with carbohydrates may increase the risk.^[18] There was no change in the ratio of saturated fat to polyunsaturated fat in the WHI intervention group.

From analyses of controlled feeding trials,^[11] it is estimated that for every 1% of energy from SFA that is replaced by 1% of energy from carbohydrate, monounsaturated fat, or polyunsaturated fat, LDL-C is lowered progressively more (1.2, 1.3, and 1.8 mg/dL, respectively). However, substituting carbs and monounsaturated fatty acid (MUFA) also tends to raise triglyceride levels, whereas a switch to polyunsaturated fats lowers triglyceride levels. According to the Jakobsen analysis, substituting monounsaturated fats for saturated fats will have a neutral effect on rates of CAD death and myocardial infarction.^[18] Dr Mozaffarian's take on the data is that "polyunsaturated fats are beneficial; monounsaturated fats are beneficial for blood lipids, but it's not clear if that translates to a reduction in CVD. If you compare saturated fats to carbs, you'll find they have a pretty neutral effect on lipids."

Culprit Carbs and Food Quality

Even those not willing to fully acquit saturated fat from the role of CV villain accept that carbohydrate consumption should be moderated. Studies like MESA and EPIC, which have shown worse metabolic and CV outcomes with higher blood levels of even-chain SFAs, implicate carbs because plasma levels of even-chain SFAs correlate more strongly with drivers of de-novo lipogenesis, including alcohol, soft drinks, and potatoes, than with dietary sources such as meat, butter, or cheese.^[16]

Small amounts of carbohydrate are typically released into the blood as glucose or converted to glycogen by the liver, but these pathways are tightly regulated such that when excess glucose hits the liver, it gets turned into fat. As explained by Dr Mozaffarian, "the biggest driver of palmitic acid (16:0) production by the liver is the dose and speed that the carb is delivered." In terms of foods, a bagel or soda consumed in isolation is more likely to trigger palmitic acid production than a small amount of potato mixed with vegetables and oil.

In light of the WHI findings, advice to lower dietary saturated fat now specifies that the substitution of saturated fat with whole grains is preferable to refined carbohydrates.^[9] And this brings us to the quality of the food the nutrient comes from.

The MESA trial showed that meat SFA was associated with greater CVD risk (hazard ratio = 1.26 for +5 g/d and 1.48 for +5% of energy, respectively), but before the vegetarians break out the champagne, the EPIC trial conducted in almost half a million middle-aged adults from 10 countries found that processed meats but not red meat per se were linked to CV mortality.^[19] Processed meat included ham, bacon, sausages, and minced meat in ready-made products. Similarly, in a study in over 37,000 Swedish men, the risk for new heart failure and death from heart failure increased by 8% and 38%, respectively, for every 50-g rise in daily processed-meat intake.^[20]

Moving Away From Macronutrients

With findings like these, there are calls to stop emphasizing macronutrients (fat, carbs, protein) in healthy-eating guidelines and to highlight real foods instead. Robert Eckel, professor of Medicine at the University of Colorado and lead author of the 2013 ACC/AHA lifestyle guidelines, agrees. "Absolutely and not good foods and bad foods; the emphasis needs to be on dietary patterns," he wrote in an email exchange with Medscape.

Among the most touted is the Mediterranean dietary pattern, which is rich in fruit, vegetables, whole grains, fatty fish, lean meat, oils, nuts, and legumes.^[21] There are supporting data for this eating pattern, including the PREDIMED trial,^[6] in which 7447 men and women free of CV disease but at high CV risk were randomly assigned to 1 of 2 Mediterranean diet groups (supplemented with either olive oil or nuts) or to a low-fat control diet. The primary endpoint of myocardial infarction, stroke, or CV death was reduced by 30% compared with the control group, largely driven by an early reduction in stroke.

In the two Mediterranean diets, 9%-10% of calories came from saturated fat, so why the stricter 5%-6% limit in the ACC/AHA lifestyle guidelines? Dr Eckel defends the recommendation, saying that "we have evidence that 5%-6% saturated fat lowers LDL-C maximally." The strongest data cited in the guidelines are from crossover feeding studies that compared a Dietary Approaches to Stop Hypertension (DASH)-type diet (5%-6% saturated fat) against a diet with 14%-15% of calories from saturated fat and showed reductions in LDL-C of 11-13 mg/dL.^[22,23,24]

Dr Mozaffarian disagrees with the guideline writing committee's conclusion. "The DASH diet is an overall dietary pattern that increased whole grain, fruits and vegetables, reduced refined carbs, included dairy. To derive a conclusion that saturated fat should be 5% of calories [from that] is not evidence based." He believes that there is little benefit to gain by pushing saturated fat below a cutpoint and that we may be better off advising people to simply increase polyunsaturated fat. There is supportive evidence for that strategy from a meta-analysis of 13 published and unpublished cohort studies on dietary linoleic acid and CAD events. Higher intakes of this omega-6 polyunsaturated fatty acid were inversely associated with risk for CAD, whether it replaced carbohydrates or saturated fat.^[25]

We Are More Than What We Eat

Teasing out the health effects of a particular food or nutrient is difficult. As Dr Nestle notes, "Diet is one factor that affects heart disease risk among many others: lifestyle, physical activity, cigarette smoking, genetics, etc." In one small study, a single aerobic exercise session appeared to counteract the postprandial endothelial dysfunction induced by a high-fat meal in apparently healthy adults.^[26] Poor diet can go hand in hand with a poor lifestyle: In the EPIC trial, those who consumed the highest amounts of processed meats were also more likely to smoke, be sedentary, and ate far fewer fruits and vegetables than other study participants.^[19]

According to Dr Mozaffarian, "Dairy is a perfect example of how focusing on single nutrients leads to silly recommendations. It's an incredibly complicated category of foods...but our guidelines for dairy are based on theory about calcium content and vitamin D. The School Lunch Program allows chocolate skim milk and banned whole milk. That's absurd. There's no evidence that whole milk is bad for kids."

So where does that leave saturated fat? According to the most recent National Health and Nutrition Examination Survey data (from 2009-2010), between 35% and 58% of American adults consumed less than 10% of total calories from saturated fat. Less than 12% met the goal from the 2013 lifestyle guidelines of less than 7% of calories from saturated fat.^[27]

Dr Mozaffarian would prefer to shift the focus to increasing healthy food consumption: "Dairy appears to be neutral for CAD and good for diabetes, processed meats are particularly harmful for diabetes and CAD, and unprocessed meats seem to be neutral." Despite disagreements regarding specific saturated fat limits and whole-fat dairy, he agrees that a Mediterranean or high-vegetable-fat DASH dietary pattern is definitely beneficial (and far better than the average American diet).

Dr Eckel concedes that helping patients adhere to a heart-healthy lifestyle is complicated, but he believes that physicians have a vital role to play. His tip: spend at least 3 minutes per patient visit on lifestyle, which should include an evaluation of the patient's dietary pattern. "A medium rare steak once a month or ice cream and cake at a birthday party should not cause dietary guilt because it is the overall diet and level of physical activity that should be repeatedly assessed and emphasized," he advises.^[28]

Disclosures

Robert Eckel, MD, reports consulting for Foodminds. Dariush Mozaffarian, MD, DrPH, reports being on the scientific advisory board of Unilever North America and receiving ad hoc honoraria or consulting fees from Bunge, Nutrition Impact, Amarin, AstraZeneca, and Life Sciences Research Organization. Marion Nestle, PhD, MPH, has authored a number of books on nutrition and food policy.

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Cite this: Saturated Fat and CAD: It's Complicated - Medscape - Feb 09, 2015.