Editor's Note: Commentary based on Wang L, Bordi PL, Fleming JA, Hill AM, Kris-Etherton PM. Effect of a moderate fat diet with and without avocados on lipoprotein particle number, size and subclasses in overweight and obese adults: a randomized, controlled trial. J Am Heart Assoc 2015;4:e001355.

Background

The 2013 American Heart Association (AHA)/American College of Cardiology (ACC) guidelines for lifestyle management to reduce cardiovascular risk recommend a reduction in saturated fatty acids (SFA) to 5-6% of total energy intake, and recommend both monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) in place of saturated fatty acids (SFA).¹ Avocados are a source of MUFA.² There is a paucity of evidence on the effect of avocado consumption on cardiovascular disease (CVD) risk factors.

The aim of this randomized, crossover, controlled feeding trial was to evaluate the effects of three cholesterol-lowering diets on lipoproteins and lipoprotein particle size. Goals included comparing a high MUFA, moderate fat diet with and without one avocado per day to a low fat diet, with implications for whether avocados have additional benefits beyond their MUFA content on lipids and lipoproteins.

Methods

This study included 45 overweight or obese adults (27 males, 18 females) that were placed on a two-week "run-in" average American diet (AAD) composed of 34% fat, 51% carbohydrate, and 16% protein. The subjects were then randomly assigned to a series of three cholesterol-lowering diet periods (five weeks each) with a two-week compliance break between diet periods. The three diet periods were as follows:

• Group 1: Low fat (LF) (24% fat, 7% SFA, 11% MUFA, 6% PUFA) )
• Group 2: Moderate fat (MF) high in MUFA (34% fat, 6% SFA, 17% MUFA, 9% PUFA)
• Group 3: Moderate fat, high in MUFA (same as group 2) plus one avocado daily (AV).

Results

Diet compliance was good as 90% of subjects consumed all the study foods and no non-study foods. All subjects maintained body weight within 2 kg.

Lipid changes are noted below:

• All three diets significantly decreased low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) versus baseline, although the reduction in TC and LDL-C by the AV diet was significantly greater {-10%, -8% P <0.0001 (both)} than the LF and MF diets.
• High density lipoprotein-cholesterol (HDL-C) decreased less (p <0.05) on AV diet and MF diet versus LF diet.
• The LF diet significantly increased triglyceride (TG) and very low-density lipoprotein (VLDL) by 17.6% and 10.9% respectively {(P <0.001 (both)}, while AV and MF did not.
• The AV and MF diets significantly decreased non-high-density lipoprotein cholesterol (non-HDL-C) {(-9.3%, -5.1%, P <0.01 (both)}, but LF did not. However, AV diet reduced non-HDL-C more (P = 0.01) than the MF diet.
• The AV and MF diets decreased apolipoprotein B100 (ApoB100), but the LF did not. Apolipoprotein A-I (ApoA-I) decreased similarly in all three diet groups. However, the ratio of ApoB/ApoA-I was lowered only by the AV diet.
• All three diets noted a reduction in number of large LDL particles (LDL-P) from baseline (P <0.001). However, the overall number of LDL-P was decreased significantly only by the AV diet (-80.1 nmol/L, P = 0.001) but not by the MF diet (-38 nmol/l, P = 0.07). Mean LDL particle size decreased on all three diets (LF -0.24 nm, P <0.0001) MF -0.21 nm, P <0.0001, and AV (-0.12 nm, P = 0.008). LDL particle size was significantly larger (P = 0.03) after the AV diet versus the LF diet. The LDL subclass results from NMR and VAP profile were in concordance. All three diets reported similar reductions in large buoyant LDL-C (LDL-C 1+2) compared to baseline (P <0.0001 for all). Only the AV diet reduced the small dense LDL-C (LDL-C 3 -4.0 mg/dL, P = 0.01; LDL3+4 -4.1 mg/dL, P = 0.04).
• All three diets decreased HDL2 versus baseline, but HDL3 was significantly decreased by LF diet but not by AV and MF diets. Total HDL particle (HDL-P) number was not changed by all three diets. Large HDL-P were decreased similarly (P <0.001) by all three diets. HDL-P size was also slightly decreased by the LF (-0.07nm), MF (-0.1nm), and AV (-0.01nm) diets compared to baseline (P <0.01 for all).
• Fasting high-sensitivity C-reactive protein (hs-CRP), insulin, glucose, and blood pressure were not changed by any diet.

Conclusion

This study shows that a cholesterol-lowering MF diet high in MUFA plus one avocado per day achieved a more favorable lipoprotein profile compared to a similar cholesterol-lowering MF diet without avocados or a low fat diet. Greater improvements in LDL-C, non-HDL-C, apo B, small dense LDL, LDL-C/HDL-C and T-C/HDL-C were noted in the Avocado diet group. Additional bioactive compounds in avocados could have exerted an important beneficial effect on CVD risk factors.

Commentary/Perspective

These data presented by Wang et al. represent the first randomized controlled feeding trial to evaluate the added lipid-lowering effect of avocados beyond their MUFA content. This is also the first study to use two advanced lipid testing methods to evaluate the impact of LF versus MF diets on lipoprotein subclass changes. A significant finding was that the AV diet lowered LDL-C, TC, LDL-P, non-HDL-C, TC/HDL-C, and LDL-C/HDL-C significantly more than a similar MF (high in MUFA) diet without one avocado daily. In comparison to the LF diet, the MF diet (high in MUFA) had more cardio-protective effects, but the AV diet had the most cardio-protective effects.

Figure 1 Avocados are a unique fruit source of monounsaturated fatty acids, low in saturated fat, no cholesterol content, and also are a rich source of vitamins, antioxidants and phytosterols, which could beneficially affect CVD risk. Some studies have been shown avocado consumption has cholesterol-lowering effect in different populations. References: 1. U.S. Department of Agriculture, Agricultural Research Service. 2010. USDA National Nutrient Database for Standard Reference, Release 23. Nutrient Data Laboratory Home Page, http://www.ars.usda.gov/ba/bhnrc/ndl

These findings suggest that the additional nutrients in avocados, including viscous fiber, plant sterols, and polyphenols, could have contributed to the added cardio-protective effect of avocados in the AV diet. Avocados are rich in plant sterols (e.g., beta sitosterol); one Haas avocado (136 g) contains 114 mg of plant sterols. In addition 100 g contains 4.8 g total fiber (2.11 g soluble fiber and 2.7 g insoluble fiber).² The authors state that in comparison to other supplementation studies, the relative dose of fiber and plant sterol in one avocado is relatively small suggesting it was the polyphenols in avocados may have exerted an independent cardio-protective effect in addition to the fatty acid content of the AV diet. This finding most importantly suggests that future studies need to be conducted to determine the cardio-protective effects of bioactive compounds including antioxidants (polyphenols, flavonoids and carotenoids) and nonantioxidants (phytosterols) found in vegetables, fruits, nuts, whole grains, and legumes.^3,4

In the Prevention with Mediterranean Diet (PREDIMED) study, nuts but not olive oil supplementation in a Mediterranean diet decreased small LDL-P.⁵ Although nuts are a good source of MUFA, phytosterols, and viscous fiber, the effect of nuts on small dense LDL-C (sdLDL-C) is not clear. Only one study showed that the addition of walnuts to the standard dietary pattern of free living subjects lowered sdLDL 13%.⁶ Lamarche et al. showed that a dietary portfolio including plant sterols, soy (1 g per 1000 kcals), viscous fiber (9 g per 1,000 kcals), soybean protein and almonds in a low SFA diet for four weeks decreased sdLDL-C (-21% P <0.01) in patients with mildly elevated LDL-C.⁷ Other studies have reported that dietary MUFA has been associated with lower sdLDL-C when substituted for SFA, although the results were not consistent.^8-10

HDL-C was decreased by all three diets in this study. However, total HDL-P remained the same. The MultiEthnic Study of Atherosclerosis (MESA) study showed that HDL-P but not HDL-C was independently associated with coronary heart disease after adjusting for LDL-P and other confounding factors.¹¹ Additional studies are needed to determine if HDL functionality is improved by a MF diet with avocados.

Overall this study confirms that Avocados have additional cardio-protective effects beyond their high MUFA content possibly due to their high content of bioactive compounds including viscous fiber, plant sterols, antioxidants, and polyphenols.

Strengths and Limitations of the Study

Strengths of this study include: well-controlled clinical trial, low drop-out rate, well designed to measure the effects of bioactive compounds in avocados beyond the fatty acids, a high level of diet compliance, and weight was maintained so as to control for the confounding effect of weight loss on lipids. Limitations include the fairly small sample size and that one avocado per day contributed a different percentage of energy over differing calorie levels (7%-13% over the six differing calorie levels prescribed for each subject's weight maintenance goal). Another limitation was that the study participants did not represent the ethnic diversity of the U.S. population.

References

1. Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2960-84.
2. Hirasawa M, Shimura K, Shimuzu A, Mura K, et al. Quantification and functional analysis of dietary fiber and polyphenols in avocado (persea Americana). J Jpn Soc Food Sci Technol 2008;55:95-101.
3. Dauchet L, Amouyel P, Hercberg S, Dallongeville J. Fruit and vegetable consumption and risk of coronary heart disease: a meta-analysis of cohort studies. J Nutr 2006;136:2588-93.
4. He FJ, Nowson CA, MacGregor GA. Fruit and vegetable consumption and stroke: meta-analysis of cohort studies. Lancet 2006;367:320-6.
5. Damasceno NR, Sala-Villa A, Cofan M, Perez-Heraz AM, et al. Mediterranean diet supplemented with nuts reduces waist circumference and shifts lipoprotein subfractions to a less atherogenic pattern in subjects at high cardiovascular risk. Atheroscerosis 2013;230:347-53.
6. Almario RU, Vongharavat V, Wong R, Kasim-Karakas SE. Effects of walnut consumption on plasma fatty acids and lipoproteins in combined hyperlidemia. Am J Clin Nutr 2001;74:72-79.
7. Lamarche B, Desroches S, Jenkins DJ, Kendall CW, et al. Combined effects of a dietary portfolio of plant sterols, vegetable protein, viscous fibre and almonds on LDL particle size. Br J Nutr 2004;92:657-63.
8. Gill GM, Brown JC, Castake MI, Wright DM, et al. Effect of dietary monounsaturated fatty acids on lipoprotein concentrations, compositions, and subfraction distributions and on VLDL apolipoprotein B kinetics: dose dependent effects on LDL. Am J Clin Nutr 2003;78:47-56.
9. Kratz M, Gulbahce E, von Eckardstein A, Cullen P, et al. Dietary mono and polyunsaturated fatty acids similarly affect LDL size in healthy men and women. J Nutr 2002;132:715-18.
10. Rivellese AA, Maffettone A, Vessby B, Uusitupa M, et al. Effects of dietary saturated, monounsaturated and n-3 fatty acids on fasting lipoproteins, LDL size, and post prandial lipid metabolism in healthy subjects. Atherosclerosis 2003;167:149-58.
11. Mackey RH, Greenland P, Goff DC, Lloyd-Jones D, et al. High-density lipoprotein cholesterol and particle concentrations, carotid atherosclerosis, and coronary events in the MESA (Multi-Ethnic Study of Atherosclerosis). J Am Coll Cardiol 2012;60:508-16.

Keywords: Adult, American Heart Association, Antioxidants, Apolipoprotein A-I, Apolipoproteins A, Apolipoproteins B, Atherosclerosis, Blood Pressure, C-Reactive Protein, Cardiovascular Diseases, Carotenoids, Edible Grain, Cholesterol, Cholesterol, LDL, Cholesterol, HDL, Coronary Disease, Diet, Fat-Restricted, Diet, Mediterranean, Energy Intake, Fabaceae, Fasting, Fatty Acids, Fatty Acids, Monounsaturated, Female, Flavonoids, Fruit, Glucose, Goals, Humans, Insulin, Juglans, Life Style, Lipids, Lipoproteins, Lipoproteins, LDL, Male, Nuts, Obesity, Particle Size, Persea, Phytosterols, Plant Oils, Polyphenols, Prunus, Risk Factors, Sample Size, Sitosterols, Soybean Proteins, Triglycerides, United States, Weight Loss, Vegetables

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