REVIEW URRENT C OPINION
Macronutrient replacement options for saturated fat: effects on cardiovascular health Michael R. Flock, Jennifer A. Fleming, and Penny M. Kris-Etherton
Purpose of review The purpose of this review is to discuss macronutrient replacement options for saturated fatty acids (SFAs) to optimize cardiovascular disease (CVD) risk reduction. Recent findings Dietary recommendations advise decreasing SFAs. There is convincing evidence that replacing SFAs with unsaturated fat, both omega-6 and omega-3 polyunsaturated fatty acids, reduces CVD risk. Monounsaturated fatty acid substitution for SFAs also decreases CVD risk. Replacing SFAs with refined carbohydrate does little to alter CVD risk, whereas whole-grain CHO or lean protein substitutions beneficially affect CVD risk. Summary Modifying the macronutrient composition of the diet by replacing SFAs with unsaturated fatty acids, as well as lean protein and carbohydrate from whole grains, all lower CVD risk. Research is needed to identify food sources of macronutrients that optimize CVD risk reduction. Keywords carbohydrates, cardiovascular disease, protein, saturated fat, unsaturated fat
INTRODUCTION Cardiovascular disease (CVD) is ranked as the top global health problem [1]. Nutrition affects many CVD risk factors. Of the top 12 risk factors recently identified by the WHO [1], many are diet-related and include high blood pressure, low fruit consumption, high BMI, high elevated plasma glucose, high salt intake and low nut/seed consumption. Dyslipidemia also contributes to CVD risk [2]. A focus of nutrition for the prevention and treatment of CVD is to decrease saturated fatty acids (SFAs) to lower LDL-cholesterol (LDL-C) and reduce CVD risk. This recommendation has continued to be central to dietary guidance for CVD risk reduction; however, the recommended macronutrient substitute for SFAs has changed. Since the first Dietary Guidelines for Americans were issued in 1980 until 2005, the recommendation was to decrease total and saturated fat with a corresponding increase in dietary carbohydrate (CHO), resulting in a low/lower fat diet. On the basis of recent epidemiologic and clinical trial research, the current recommendation is to replace SFAs with unsaturated fat calories resulting in a moderate-fat diet. Questions remain about specific recommendations for monounsaturated fatty acids (MUFAs) and
polyunsaturated fatty acids (PUFAs), including omega-6 (n-6) and omega-3 (n-3) fatty acids. Questions also have been raised about specific food sources (i.e. nuts and avocados) of unsaturated fat that might provide additional cardiovascular benefits because of their micronutrient and bioactive profile. There is new evidence about substituting protein for SFAs, and specifically what type of protein (i.e. plant versus animal) elicits the greatest CVD benefits. There are still questions about dietary CHO as a substitute for SFA since many different food sources deliver various micronutrients, fiber and other bioactives (e.g. whole grains) that could reduce CVD risk. This review discusses the optimal macronutrient substitutes for SFA to reduce CVD risk. Since CVD is multifactorial, a deeper understanding is needed about the amounts and types of unsaturated fatty Department of Nutritional Sciences, The Pennsylvania State University, Pennsylvania, USA Correspondence to Penny M. Kris-Etherton, Department of Nutritional Sciences, 319 Chandlee Lab, Penn State University, University Park, PA 16802, USA. Tel: +1 814 863 2923; e-mail: [email protected] Curr Opin Lipidol 2014, 25:67–74 DOI:10.1097/MOL.0000000000000039
0957-9672 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
www.co-lipidology.com
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Nutrition and metabolism
KEY POINTS
evidence on the effects of replacing SFAs with PUFAs [11–19] as well as other macronutrients [20,21 ]. A meta-analysis of eight randomized controlled trials (RCTs) reported each 5% calorie increase in PUFA as a replacement for SFA decreased coronary heart disease (CHD) events by 10% [8]. Collectively, these studies reported a 19% reduction in CHD events when SFA was replaced with PUFA, largely attributed to improved blood lipids/lipoproteins [8]; replacing SFA with PUFA, specifically n-6, reduces LDL-C [9,22]. Six of the eight RCTs only included men [11–16], highlighting a need for studies in both sexes. Moreover, only three of the RCTs replaced SFA with solely n-6 PUFA, whereas the other five replaced SFA with a mixture of n-6 and n-3 PUFA. The studies using mixed n-6 and n-3 PUFA reduced CHD events by 22% [23]. &&
SFAs increase LDL-C and increase risk of CVD. Replacing SFAs with unsaturated fat, particularly omega-6 and omega-3 polyunsaturated fatty acids, and also MUFA reduces CVD risk. Whole grain carbohydrates and lean protein foods reduce CVD risk when substituted for SFAs. An emerging frontier is to better understand how food sources of macronutrients and their accompanying bioactives further decrease CVD risk.
acids, CHO and proteins, and food sources of these macronutrients that should replace SFAs in the diet. This subject is timely given the recent release of the 2013 Guidelines on Lifestyle Management to Reduce Cardiovascular Risk by the American Heart Association (AHA) and the American College of Cardiology (ACC) that recommends adults who would benefit from LDL-C lowering should aim for a dietary pattern that achieves 5-6% of calories from SFA [3 ]. Understanding the effects of different macronutrient substitutions for SFA on CVD risk factors will enable implementation of diet intervention strategies to further decrease CVD risk.
Omega-6 polyunsaturated fatty acids
Individual SFAs have different effects on lipids and lipoproteins. In a meta-analysis, all SFAs except stearic acid increased LDL-C and HDL-C [4]. Lauric acid has the greatest LDL-C-raising effect, but decreases the total cholesterol (TC)/HDL-C by virtue of causing the greatest increase in HDL-C. Myristic and palmitic acid increase LDL-C and HDL-C comparably with little effect on the TC/HDL-C [4]. These findings agree with a more recent review that reported the dose-dependent effects of individual SFAs on lipids and lipoproteins [5]. Irrespective of the potency of different SFAs on lipids and lipoproteins, the objective is to decrease dietary SFAs for CVD risk reduction. A recent Cochrane review reported that reducing SFAs lowered the risk of cardiovascular events by 14% [6 ]. Replacing SFAs with unsaturated fat appeared to benefit cardiovascular events, although the ideal type of unsaturated fat was unclear [6 ].
The AHA concluded that at least 5–10% of calories from n-6 PUFA, particularly linoleic acid, decreases CHD risk, and lowering n-6 PUFA may increase risk [10]. However, some groups recommend reductions in n-6 PUFA intake [23–25,26 ]. The rationale for lowering n-6 PUFA intake, particularly linoleic acid, was based on the belief that linoleic acid increased tissue concentrations of arachidonic acid, thereby promoting a proinflammatory eicosanoid response [24]. However, variations in dietary linoleic acid intake in healthy adults do not substantially affect tissue concentrations of arachidonic acid [27], and linoleic acid is not proinflammatory in the range of current intakes [22,28,29]. Some have recommended that n-6 PUFA be decreased because of an abundance of oxidized linoleic acid metabolites in oxidized LDL, which is more atherogenic than unmodified LDL [26 ,30]. In a reanalysis of the Sydney Diet Heart Study [26 ], the high n6 PUFA group (15% of calories as PUFA) had a higher risk of all-cause mortality [hazard ratio 1.62, 95% confidence interval (CI) 1.00–2.64], and CVD mortality (1.70, 1.03–2.80) and CHD (1.74, 1.04– 2.92) compared with the control group (no specific dietary instruction). Importantly, however, transfatty acids (TFAs) consistently increase CVD risk [31–33], and were not measured in this study. The intervention participants were provided safflower oil margarine tosubstituteforanimal fats [26 ];therefore, the use of a margarine-based intervention containing TFAs could have contributed to the unfavorable effects reported for the high n-6 PUFA group.
Polyunsaturated fatty acids
Omega-3 polyunsaturated fatty acids
Clinical, epidemiological, and mechanistic studies consistently show that substituting PUFAs for SFAs reduces CVD risk [7–10]. Table 1 presents trial
Marine-derived omega-3 (n-3) PUFAs [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] are inversely related to CHD mortality [34–36].
&&
EVIDENCE FOR REPLACING SATURATED FATTY ACIDS
&&
&&
68
www.co-lipidology.com
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Volume 25 Number 1 February 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Macronutrient replacement options for saturated fat Flock et al. Table 1. Randomized controlled trials testing the effect of macronutrients replacing SFA on risk of MI or CHD death Age (% men)
Study
% kcal replaced
N
Indication
Duration (years)
Intervention
RR (95% CI)
PUFA replacing SFA Rose Corn Oil (1965) [17]
52
n/a
54–88 (100)
Macronutrient replacement options for saturated fat: effects on cardiovascular health Michael R. Flock, Jennifer A. Fleming, and Penny M. Kris-Etherton
Purpose of review The purpose of this review is to discuss macronutrient replacement options for saturated fatty acids (SFAs) to optimize cardiovascular disease (CVD) risk reduction. Recent findings Dietary recommendations advise decreasing SFAs. There is convincing evidence that replacing SFAs with unsaturated fat, both omega-6 and omega-3 polyunsaturated fatty acids, reduces CVD risk. Monounsaturated fatty acid substitution for SFAs also decreases CVD risk. Replacing SFAs with refined carbohydrate does little to alter CVD risk, whereas whole-grain CHO or lean protein substitutions beneficially affect CVD risk. Summary Modifying the macronutrient composition of the diet by replacing SFAs with unsaturated fatty acids, as well as lean protein and carbohydrate from whole grains, all lower CVD risk. Research is needed to identify food sources of macronutrients that optimize CVD risk reduction. Keywords carbohydrates, cardiovascular disease, protein, saturated fat, unsaturated fat
INTRODUCTION Cardiovascular disease (CVD) is ranked as the top global health problem [1]. Nutrition affects many CVD risk factors. Of the top 12 risk factors recently identified by the WHO [1], many are diet-related and include high blood pressure, low fruit consumption, high BMI, high elevated plasma glucose, high salt intake and low nut/seed consumption. Dyslipidemia also contributes to CVD risk [2]. A focus of nutrition for the prevention and treatment of CVD is to decrease saturated fatty acids (SFAs) to lower LDL-cholesterol (LDL-C) and reduce CVD risk. This recommendation has continued to be central to dietary guidance for CVD risk reduction; however, the recommended macronutrient substitute for SFAs has changed. Since the first Dietary Guidelines for Americans were issued in 1980 until 2005, the recommendation was to decrease total and saturated fat with a corresponding increase in dietary carbohydrate (CHO), resulting in a low/lower fat diet. On the basis of recent epidemiologic and clinical trial research, the current recommendation is to replace SFAs with unsaturated fat calories resulting in a moderate-fat diet. Questions remain about specific recommendations for monounsaturated fatty acids (MUFAs) and
polyunsaturated fatty acids (PUFAs), including omega-6 (n-6) and omega-3 (n-3) fatty acids. Questions also have been raised about specific food sources (i.e. nuts and avocados) of unsaturated fat that might provide additional cardiovascular benefits because of their micronutrient and bioactive profile. There is new evidence about substituting protein for SFAs, and specifically what type of protein (i.e. plant versus animal) elicits the greatest CVD benefits. There are still questions about dietary CHO as a substitute for SFA since many different food sources deliver various micronutrients, fiber and other bioactives (e.g. whole grains) that could reduce CVD risk. This review discusses the optimal macronutrient substitutes for SFA to reduce CVD risk. Since CVD is multifactorial, a deeper understanding is needed about the amounts and types of unsaturated fatty Department of Nutritional Sciences, The Pennsylvania State University, Pennsylvania, USA Correspondence to Penny M. Kris-Etherton, Department of Nutritional Sciences, 319 Chandlee Lab, Penn State University, University Park, PA 16802, USA. Tel: +1 814 863 2923; e-mail: [email protected] Curr Opin Lipidol 2014, 25:67–74 DOI:10.1097/MOL.0000000000000039
0957-9672 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
www.co-lipidology.com
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Nutrition and metabolism
KEY POINTS
evidence on the effects of replacing SFAs with PUFAs [11–19] as well as other macronutrients [20,21 ]. A meta-analysis of eight randomized controlled trials (RCTs) reported each 5% calorie increase in PUFA as a replacement for SFA decreased coronary heart disease (CHD) events by 10% [8]. Collectively, these studies reported a 19% reduction in CHD events when SFA was replaced with PUFA, largely attributed to improved blood lipids/lipoproteins [8]; replacing SFA with PUFA, specifically n-6, reduces LDL-C [9,22]. Six of the eight RCTs only included men [11–16], highlighting a need for studies in both sexes. Moreover, only three of the RCTs replaced SFA with solely n-6 PUFA, whereas the other five replaced SFA with a mixture of n-6 and n-3 PUFA. The studies using mixed n-6 and n-3 PUFA reduced CHD events by 22% [23]. &&
SFAs increase LDL-C and increase risk of CVD. Replacing SFAs with unsaturated fat, particularly omega-6 and omega-3 polyunsaturated fatty acids, and also MUFA reduces CVD risk. Whole grain carbohydrates and lean protein foods reduce CVD risk when substituted for SFAs. An emerging frontier is to better understand how food sources of macronutrients and their accompanying bioactives further decrease CVD risk.
acids, CHO and proteins, and food sources of these macronutrients that should replace SFAs in the diet. This subject is timely given the recent release of the 2013 Guidelines on Lifestyle Management to Reduce Cardiovascular Risk by the American Heart Association (AHA) and the American College of Cardiology (ACC) that recommends adults who would benefit from LDL-C lowering should aim for a dietary pattern that achieves 5-6% of calories from SFA [3 ]. Understanding the effects of different macronutrient substitutions for SFA on CVD risk factors will enable implementation of diet intervention strategies to further decrease CVD risk.
Omega-6 polyunsaturated fatty acids
Individual SFAs have different effects on lipids and lipoproteins. In a meta-analysis, all SFAs except stearic acid increased LDL-C and HDL-C [4]. Lauric acid has the greatest LDL-C-raising effect, but decreases the total cholesterol (TC)/HDL-C by virtue of causing the greatest increase in HDL-C. Myristic and palmitic acid increase LDL-C and HDL-C comparably with little effect on the TC/HDL-C [4]. These findings agree with a more recent review that reported the dose-dependent effects of individual SFAs on lipids and lipoproteins [5]. Irrespective of the potency of different SFAs on lipids and lipoproteins, the objective is to decrease dietary SFAs for CVD risk reduction. A recent Cochrane review reported that reducing SFAs lowered the risk of cardiovascular events by 14% [6 ]. Replacing SFAs with unsaturated fat appeared to benefit cardiovascular events, although the ideal type of unsaturated fat was unclear [6 ].
The AHA concluded that at least 5–10% of calories from n-6 PUFA, particularly linoleic acid, decreases CHD risk, and lowering n-6 PUFA may increase risk [10]. However, some groups recommend reductions in n-6 PUFA intake [23–25,26 ]. The rationale for lowering n-6 PUFA intake, particularly linoleic acid, was based on the belief that linoleic acid increased tissue concentrations of arachidonic acid, thereby promoting a proinflammatory eicosanoid response [24]. However, variations in dietary linoleic acid intake in healthy adults do not substantially affect tissue concentrations of arachidonic acid [27], and linoleic acid is not proinflammatory in the range of current intakes [22,28,29]. Some have recommended that n-6 PUFA be decreased because of an abundance of oxidized linoleic acid metabolites in oxidized LDL, which is more atherogenic than unmodified LDL [26 ,30]. In a reanalysis of the Sydney Diet Heart Study [26 ], the high n6 PUFA group (15% of calories as PUFA) had a higher risk of all-cause mortality [hazard ratio 1.62, 95% confidence interval (CI) 1.00–2.64], and CVD mortality (1.70, 1.03–2.80) and CHD (1.74, 1.04– 2.92) compared with the control group (no specific dietary instruction). Importantly, however, transfatty acids (TFAs) consistently increase CVD risk [31–33], and were not measured in this study. The intervention participants were provided safflower oil margarine tosubstituteforanimal fats [26 ];therefore, the use of a margarine-based intervention containing TFAs could have contributed to the unfavorable effects reported for the high n-6 PUFA group.
Polyunsaturated fatty acids
Omega-3 polyunsaturated fatty acids
Clinical, epidemiological, and mechanistic studies consistently show that substituting PUFAs for SFAs reduces CVD risk [7–10]. Table 1 presents trial
Marine-derived omega-3 (n-3) PUFAs [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] are inversely related to CHD mortality [34–36].
&&
EVIDENCE FOR REPLACING SATURATED FATTY ACIDS
&&
&&
68
www.co-lipidology.com
&
&
&
&
Volume 25 Number 1 February 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Macronutrient replacement options for saturated fat Flock et al. Table 1. Randomized controlled trials testing the effect of macronutrients replacing SFA on risk of MI or CHD death Age (% men)
Study
% kcal replaced
N
Indication
Duration (years)
Intervention
RR (95% CI)
PUFA replacing SFA Rose Corn Oil (1965) [17]
52
n/a
54–88 (100)
