Journal of Clinical Lipidology (2015) 9, 58–64
Statins and almonds to lower lipoproteins (the STALL Study) Janelle F. Ruisinger, PharmD*, Cheryl A. Gibson, PhD, James M. Backes, PharmD, Bryan K. Smith, PhD, CSCS, Debra K. Sullivan, PhD, RD, Patrick M. Moriarty, MD, Penny Kris-Etherton, PhD, RD Department of Pharmacy Practice, University of Kansas School of Pharmacy, Kansas City, KS, USA (Drs Ruisinger and Backes); Department of Internal Medicine, Division of General and Geriatric Medicine, University of Kansas Medical Center, Kansas City, KS, USA (Dr Gibson); Department of Kinesiology and Health Education, Southern Illinois University Edwardsville, Vadalabene Center, Edwardsville, IL, USA (Dr Smith); Department of Dietetics and Nutrition, University of Kansas Medical Center, Kansas City, KS, USA (Dr Sullivan); Department of Medicine, Division of Clinical Pharmacology, University of Kansas Medical Center, Atherosclerosis and LDL–Apheresis Center, Kansas City, KS, USA (Dr Moriarty); and Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA, USA (Dr Kris-Etherton) KEYWORDS: Almonds; Lipoproteins; Nuts; Cholesterol; Statins
BACKGROUND: Dietary supplementation with almonds has demonstrated dose-dependent decreases in low-density lipoprotein cholesterol (LDL-C), likely because of their composition of beneficial nutrients including mono- and polyunsaturated fatty acids, fiber, and protein. OBJECTIVE: The primary objective of this study was to determine the changes in the lipid profile (LDL-C, high-density lipoprotein cholesterol [HDL-C], triglycerides, total cholesterol, non–HDL-C), LDL-C particle size, and lipoprotein (a) when 100 g of almonds daily were added to background statin therapy for 4 weeks. METHODS: Subjects (N 5 48) receiving a consistent statin dose were randomized to 100 g of almonds daily and to The National Cholesterol Education Program Adult Treatment Panel’s third report Therapeutic Lifestyle Changes Diet counseling (almond group; n 5 22) or solely Adult Treatment Panel’s third report Therapeutic Lifestyle Changes Diet counseling (non-almond group; n 5 26), for 4 weeks. RESULTS: No significant changes in weight and weekly physical activity were noted between the 2 groups from baseline. However, the almond group consumed significantly more calories at 4 weeks compared with controls. The almond group experienced a 4.9% reduction in non–HDL-C compared with a 3.5% increase for the non-almond group (P 5 .02). Additionally, notable improvements were observed in LDL-C and triglycerides, but did not achieve statistical significance (P 5 .068 for both parameters). There was also a shift from LDL pattern A to pattern B particles (P 5 .003) in the almond group. No significant differences in total cholesterol (P 5 .1), HDL-C (P 5 .3), or lipoprotein (a) (P 5 .1) were observed. CONCLUSION: Adding 100 g of almonds daily to chronic statin therapy for 4 weeks significantly reduced non–HDL-C. Trial registration: clinicaltrials.gov Identifier: NCT00603876. Ó 2015 National Lipid Association. All rights reserved.
* Corresponding author. J3901 Rainbow Blvd, Mail Stop 4047, Kansas City, KS 66160.
E-mail address: [email protected] Submitted July 1, 2014. Accepted for publication October 2, 2014.
1933-2874/$ - see front matter Ó 2015 National Lipid Association. All rights reserved. http://dx.doi.org/10.1016/j.jacl.2014.10.001
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Introduction Coronary heart disease (CHD) continues to be the leading cause of morbidity and mortality in the United States, affecting an estimated 16.3 million individuals $20 years old or approximately 7% of the total population.1 Elevated low-density lipoprotein cholesterol (LDL-C) is a major modifiable risk factor for CHD. The National Cholesterol Education Program Adult Treatment Panel’s third report (ATP-III), the National Lipid Association (NLA) Recommendations for Patient-centered Management of Dyslipidemia: Part 1 – Executive Summary, and the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the ACC/AHA Task Force on Practice Guidelines, all focus on evidence demonstrating the importance of LDL-C reduction to decrease CHD risk.2–4 Furthermore, ATP-III identifies non–high-density lipoprotein cholesterol (non-HDL-C) as a secondary target in patients with triglycerides (TG) $200 mg/dL, whereas the NLA classifies non–HDL-C as a primary target to reduce CHD risk.2,3 Additionally, the ATP-III guidelines consider lipoprotein(a) [Lp(a)] as an emerging risk factor that has been linked to CHD risk.2 In addition to focusing on lipid biomarkers, ATP-III also emphasizes a healthy diet and regular exercise for patients regardless of LDL-C to decrease their risk for CHD.2 This healthy lifestyle is also supported by the more recent NLA Recommendations and the ACC/AHA Guideline on Lifestyle Management to Reduce Cardiovascular Risk.3,5 Therapeutic Lifestyle Changes (TLC) described in ATP-III advocate a comprehensive lifestyle approach to CHD risk reduction.2 In addition to weight reduction and physical activity, ATP-III promotes the TLC Diet. This approach emphasizes a reduction in saturated fatty acids (,7% of total daily calories) and moderate consumption of unsaturated fats, specifically monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA). Diets considered ‘‘heart healthy’’ (ie, Mediterranean Diet) frequently replace saturated fats with foods high in unsaturated fat such as nuts and olive oil. One hundred grams of almonds contain approximately 32 g of MUFA, 12 g of PUFA, and 4 g of saturated fatty acids.6 Additionally, almonds contain fiber, plant protein, phytochemicals, and sterols, all of which may contribute to their beneficial effects on lipoproteins.7,8 Although almonds are high in unsaturated fats, protein, and fiber, they are also energy-dense (Table 1).6 One hundred grams of almonds contain approximately 579 kcal.6 Thus, patients may risk gaining weight when adding them to their habitual diet. However, studies in general have not found significant increases in weight with varying amounts of almond intake.9–16 It has been proposed that the protein and fiber content of almonds promotes satiety, therefore decreasing caloric intake from other foods and reducing the propensity for weight gain.16,17
59 Table 1
Nutrient profile of almonds
Nutrient
Amount/100 g
Energy (kcal) Protein (g) Total fat (g) Saturated fatty acids (g) Monounsaturated fatty acids (g) Polyunsaturated fatty acids (g) Carbohydrate (g) Fiber (g) Sugars (g)
579 21.2 49.9 3.8 31.5 12.3 21.6 12.5 4.4
For most patients, statins are the cornerstone for LDL-C reduction. However, because of aggressive LDL-C treatment goals, cost, and dose-dependent side effects associated with statins, additional therapy may be required to achieve optimal LDL-C levels. One option that may further reduce LDL-C levels when added to statin therapy is incorporating almonds in a heart-healthy diet. Almonds induce a dose-dependent LDL-C lowering when consumption is .50 g daily.8 To our knowledge, no study has assessed the lipid-lowering effects of almonds when added to statin therapy. Although 1 study by Jenkins et al, included 2 patients on statin therapy in their assessment of almonds in hyperlipidemic patients, the small sample size precludes definitive conclusions.9 We hypothesized that consumption of 100 g of almonds daily would significantly and favorably affect LDL-C, HDL-C, TG, total cholesterol (TC), non–HDL-C, LDL-C particle size, and Lp(a) when added to chronic statin therapy.
Methods Subjects aged 18 to 78 years taking chronic statin therapy, defined as a consistent statin dose for at least 8 weeks before study entry with continuation of the same dose during the 4-week study period, were eligible. Exclusion criteria included: LDL-C levels ,70 mg/dL, the use of lipid-lowering agents other than statins, adherence to specialized diets, nut consumption greater than twice weekly, nut allergies, liver disease, chronic renal or CHD, and alcohol or illicit drug dependence. Postmenopausal women were allowed study entry if not taking hormone replacement therapy or on a consistent hormone replacement therapy dose. Females of child-bearing potential using an effective form of contraception were allowed to participate. Subjects meeting eligibility criteria were randomized to 100 g of almonds daily and ATP-III TLC Diet counseling (almond group) or solely ATP-III TLC Diet counseling (non-almond group). The University of Kansas Medical Center Human Subjects Committee, which serves as the institutional review board, approved the study, and all subjects signed informed consent before study enrollment. This study was registered at Clinicaltrials.gov as NCT00603876.
60 Fasting plasma concentrations of LDL-C, HDL-C, TG, very LDL-C (VLDL-C), and Lp(a) were directly measured by Atherotech Diagnostics Lab using the inverted rate zonal, single verticle spin, ultra-centrifugation based Vertical Auto Profile method.18 This was a single-site, 2-arm pilot study comparing the effects of almond consumption for 4 weeks (after a 1-week screening period) to no almond consumption. All subjects were instructed to maintain their current diet during the screening period (week 0) and complete a 3-day food record. At week 1, subjects returned for their second visit, which included randomization, fasting lipid panel, LDL-C particle size, Lp(a) measurements, and biometric measurements (blood pressure, weight, height, and waist circumference). Also during week 1, all subjects received ATP-III TLC Diet counseling via telephone from a registered dietitian who reviewed their initial 3-day food record. Subjects randomized to treatment received further instruction on how to compensate for the added calories from the almonds. Whole California almonds were supplied as raw and unsalted in preweighed 100 g individual packages. Food intake was again recorded (via 3-day food record) by the subjects at weeks 2 and 4. For each of the 3 food records, subjects were required to document all food and drink consumed for 3 consecutive days including 1 weekend day. Dietary intake data were collected and analyzed using Nutrition Data System for Research software, version 2010, developed by the Nutrition Coordinating Center, University of Minnesota, Minneapolis, MN. Adherence was assessed at week 4 by counting unconsumed packages of almonds. Physical activity for each subject was also assessed at screening (week 0) and week 4 using the Physical Activity Questionnaire.19 Subjects were instructed to maintain their current activity level and exercise routines during the study period. To compare mean values, t-tests were used to determine statistical significance between treatments. Analysis of variance, Fisher’s exact, and Pearson chi-square tests, as appropriate, were employed to assess differences in characteristics of subjects, such as LDL subclass patterns A and B. Statistical significance was accepted at P , .05. Statistical analyses were performed with the SPSS PC1 (Statistical Package for the Social Sciences) software (SPSS version 14, Chicago, IL).
Results Fifty subjects were enrolled, and 22 subjects in the almond group and 26 subjects in the non-almond group completed the study. Two subjects in the almond group withdrew because of the inability to consume the almonds daily and concerns about the additional energy intake. Of those who completed the study, the mean age was about 60 years and 50% were female. Baseline characteristics did not differ between the 2 groups (Table 2). Adherence to almond consumption was .95%.
Journal of Clinical Lipidology, Vol 9, No 1, February 2015 Table 2 Baseline characteristics for all subjects completing the study*
Variables
ATP-III TLC Diet counseling 1 almonds
Age (y) 60.0 6 10.4 Gender Female 10 Male 12 Weight (lb) 191.3 6 29.4 BMI (kg/m2) 29.8 6 4.8 Waist circumference (in) 39.9 6 4.9 Blood pressure (mm/Hg) Systolic 123 6 16 Diastolic 79 6 8 Chronic conditions Hypertension 9 Type 2 diabetes 1 mellitus Mean daily statin dose (mg) Atorvastatin 16.7 (n 5 3) Lovastatin 40 (n 5 2) Pravastatin 40 (n 5 1) Rosuvastatin 20 (n 5 2) Simvastatin 30 (n 5 14) Plasma lipids (mg/dL) Total cholesterol 171.4 6 27.1 LDL-C 101.0 6 22.0 HDL-C 51.9 6 13.6 Triglycerides 102.8 6 37.7 Non-HDL 119.3 6 23.2 Lp(a) 7.8 6 3.3 IDL 8.9 6 5.6 Energy consumed 1729 6 429 (kcal/day) Physical activity 1341 6 1675 (kcal/wk)
ATP-III TLC Diet counseling 59.3 6 11.7 14 12 179.2 6 31.5 28.6 6 3.9 37.6 6 4.5 119 6 14 77 6 10 12 3
22 (n 5 5) 20 (n 5 1) 33.3 (n 5 3) 7.5 (n 5 2) 36.7 (n 5 15) 175.4 102.5 54.7 103.4 120.5 9.0 10.3 1820
6 6 6 6 6 6 6 6
30.6 24.5 14.1 49.7 27.2 6.5 6.9 585
1813 6 1365
ATP-III TLC, Adult Treatment Panel’s third report Therapeutic Lifestyle Changes; BMI, body mass index; HDL-C, high-density lipoprotein cholesterol; IDL, intermediate-density lipoprotein; LDL-C, low-density lipoprotein cholesterol; Lp(a), lipoprotein(a). Data are expressed as mean 6 standard deviation. *No differences noted between groups.
At study close, there were no significant differences in weight, body mass index, or physical activity between the 2 study groups (Table 3). A significant difference between the almond group and non-almond groups was found in non– HDL-C with a 4.9% decrease among the almond group from baseline compared with a 3.5% increase for the non-almond group (P 5 .024). The almond group had notable improvements in LDL-C and TG, but these did not achieve statistical significance (P 5 .068 and .068, respectively) (Table 3). The change in VLDL was statistically significant (P 5 .01), with the VLDL levels among the non-almond group increasing 12.7%, whereas the levels in the almond group decreased by 3.3%. The almonds also significantly affected LDL pattern type, which resulted in a
Ruisinger et al Table 3
The STALL Study
61
Changes in body weight, lipoprotein parameters, and calories burned from baseline to 4 weeks
Parameter
Week
ATP-III TLC Diet counseling 1 almonds
Weight (lb)
0 4 0 4
191.3 192.1 29.8 30.0
6 6 6 6
29.4 29.2 4.8 4.8
179.2 179.0 28.6 28.5
6 6 6 6
31.5 32.0 3.9 4.0
0 4 0 4 0 4 0 4 0 4 0 4 0 4 0 4
171.4 165.6 101.0 95.6 51.9 52.2 102.8 102.1 18.4 17.8 119.3 113.4 7.8 7.5 8.9 7.8
6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6
27.1 31.3 22.0 23.9 13.6 13.8 37.7 38.3 3.7 4.0 23.2 24.5 3.3 3.7 5.6 5.5
175.4 177.2 102.5 104.3 54.7 52.4 103.4 115.0 18.1 20.4 120.5 124.7 9.0 8.9 10.3 12.0
6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6
30.7 23.7 24.5 18.7 14.1 11.0 49.7 42.6 5.7 5.1 27.2 20.8 6.5 6.1 6.9 4.5
0 4 0 4 0 4 0 4
13 9 7 7 2 6 1341 6 1675 1481 6 2246
BMI (kg/m2) Lipids (mg/dL) TC LDL-C HDL-C Triglycerides VLDL-C Non-HDL-C Lp(a) IDL-C Pattern (n, %) A AB B Physical activity (kcal/week)
ATP-III TLC Diet counseling
18 18 4 4 4 4 1813 6 1365 1674 6 1265
P value .145 .262
.102 .068 .347 .068 .01* .024 .109 .004
.003† .311
ATP-III TLC, Adult Treatment Panel’s third report Therapeutic Lifestyle Changes; BMI, body mass index; HDL-C, high-density lipoprotein cholesterol; IDL-C, intermediate-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; Lp(a), lipoprotein(a); TC, total cholesterol; VLDL, very low-density lipoprotein cholesterol. Data are expressed as mean 6 standard deviation. *The change in VLDL-C is significant for the non-almond group only. †The change in distribution of pattern type is significant for the almond group only.
shift from pattern A to pattern B (P 5 .003). There were no differences in TC, HDL-C, or Lp(a) between the 2 groups from baseline (Table 3). Subjects in the almond group reported overall higher daily energy intake as well as overall higher daily intake of total fat, saturated fat, MUFA, PUFA, total protein, vegetable protein, and insoluble fiber at end of study compared with controls (P , .05) (Table 4).
Discussion The results of this study demonstrate that adding 100 g of almonds daily can significantly lower non–HDL-C in subjects on statin therapy and elicit beneficial trends in other lipoprotein parameters. Compared with LDL-C, our findings suggest that non–HDL-C more consistently predicts coronary events.20 Therefore, consistent almond consumption could be used as a strategy to lower non– HDL-C and further reduce CHD risk for patients on statin
therapy. Additionally, adding almonds may be especially appealing to patients unwilling or unable to take higher statin doses. Body weight did not increase significantly during 4 weeks of consuming 100 g of almonds daily, despite higher daily energy intake. This is consistent with data from Spiller et al, who also demonstrated in 2 separate studies that 100 g of almonds daily for 4 weeks did not appreciably affect weight.10,11 In contrast, another study evaluating 2 oz of almonds (w57 g) daily for 6 months in 81 subjects caused statistically significant weight gain (1.43 pounds) in men but not women.21 The authors concluded this weight gain was slight and likely biologically insignificant. Furthermore, another study observed statistically significant weight gain in 20 healthy subjects consuming 100 g of almonds daily for 4 weeks.22 Similar to our study, however, several other studies have shown that diet supplementation with varying amounts of almonds does not significantly affect body weight.9–16 It is likely that,
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Journal of Clinical Lipidology, Vol 9, No 1, February 2015
Table 4 Changes in caloric intake and select nutrients for almond and non-almond groups from baseline to 4 weeks
Item Energy intake (kcal/day) Total fat (g/d) Total protein (g/d)
ATP-III TLC Diet ATP-III counseling 1 TLC Diet counseling Week almonds
P value
0
1729 6 429
1820 6 585 NS
4 0 4 0
2031 6 477 74 111 79
1771 6 521 .003* 70 NS 60 .00 79 NS
4 0
90 24
73 24
.01 NS
4 0 4 0 4 0
25 28 53 16 24 12
20 26 23 16 13 16
.05 NS .00 NS .00 NS
4 Vegetable 0 protein (g/d) 4
20 23
16 28
.04 NS
39
27
.00
Saturated fat (g/d) MUFA (g/d) PUFA (g/d) Insoluble fiber (g/d)
ATP-III TLC, Adult Treatment Panel’s third report Therapeutic Lifestyle Changes; MUFA, monounsaturated fatty acids; NS, not significant; PUFA, polyunsaturated fatty acids. Energy intake expressed as mean 6 standard deviation. *Change in energy intake is significant for the almond group only.
although almonds are energy-dense, the protein, unsaturated fat, and fiber content cause satiation, preventing the subjects from consuming additional calories. However, it is still important that patients consume almonds in place of other calorie sources and not simply add them to habitual caloric intake. Moreover, because the energy content of almonds was recently shown to be significantly less than the energy density as determined using the Atwater factor, it is likely that subjects absorbed fewer calories from the ingested almonds than would be expected.17 Our study also demonstrated that adding almonds to statin therapy produced favorable trends in LDL-C and TG. Several other studies have shown significant decreases in LDL-C with the addition of varying amounts of almonds,9–11,13,14,22–25 and a meta-analysis by Phung et al reported that almonds strongly trend toward significantly lowering LDL-C.26 However, to our knowledge, none of these studies focused on subjects already taking statin therapy. In addition, subjects in the present study had a mean baseline LDL-C of 102 6 23 mg/dL. Two separate studies by Spiller et al using 100 g of almonds daily for 4 weeks demonstrated a significant reduction in LDL-C, but subjects had a baseline LDL-C of 166 6 26 mg/dL and 156 6 28 mg/dL, respectively.10,11 Our data showed a trend
toward LDL-C lowering, but the lack of statistical significance is likely a consequence of low baseline LDL-C resulting from the concurrent statin therapy. Similar to other almond studies, our study was 4 weeks in duration. However, it is possible that extending the study period would produce greater lipoprotein reductions. Hyson et al demonstrated that subjects consuming 66 6 5 g of almonds daily for 6 weeks produced a statistically significant 6% and 14% reduction in LDL-C and TG, respectively.23 We speculate that a smaller daily quantity of almonds for a longer duration may produce comparable or greater lipoprotein effects. Additionally, consuming almonds for a longer duration may produce significant changes in HDL-C. As previous studies suggest, other therapies require a longer duration to observe improvements in HDL-C.27,28 Most studies have shown that almonds do not affect TG. However, 1 study demonstrated that approximately 66 g of almonds daily significantly decreased TG.23 The nonsignificant TG and VLDL-C reductions in our study contributed to the significant reduction in non–HDL-C. These differing results may reflect the high overall variability of TGs, as observed in studies and clinical practice. Additionally, subjects in our study did not experience a change in Lp(a). In contrast, 1 study (n 5 27) showed a significant 7.8% reduction in Lp(a) with 73 g of almonds daily for 4 weeks.9 However, similar to our study, Damasceno et al showed no effect on Lp(a) in 18 subjects consuming 50 to 75 g of almonds for 4 weeks, nor did Jalali-Khanabadi et al in 30 subjects consuming 60 g of almonds daily for 4 weeks.13,24 This study demonstrated a statistically significant shift from pattern A (larger, buoyant LDL-C particles) to pattern B (smaller, dense LDL-C particles) (P 5 .003). This is an unexpected finding because several studies, including a recent study by Parlesak et al, demonstrated decreased small, dense LDL-C levels with increased MUFA consumption.29 Our subjects in the almond group consumed significantly more MUFA compared with the non-almond group (Table 4). However, a study by Lamarche et al30 demonstrated that a diet including plant sterols, viscous fiber, soybean protein, and almonds did not significantly affect LDL-C particle size, but suggested a shift from large LDL-C particles to smaller LDL-C particles. Although the clinical significance of LDL-C particle size is emerging, a growing evidence base suggests that smaller LDL-C particles are associated with higher CHD risk.31–33 However, a panel of lipid experts concluded in a 2011 publication that ‘‘there is no evidence that a shift in LDL subfractions directly translates into change in disease progression or improved outcome.’’34 The LDL-C particle size shift realized in the almond group is an unexpected finding that warrants further investigation.
Strengths Strengths to this study include subjects’ high adherence to consuming the almonds (.95%). In the future, it would be interesting to assess if adherence to almonds for
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lowering lipoproteins is higher than that of statins because the adherence to statin therapy is often low. A second strength is the low dropout rate. Only two subjects withdrew from the study because of an inability to consume almonds daily. All other subjects completed the study.
Limitations Limitations to this study include the relatively small sample size (n 5 48), which may have precluded detection of significant changes in LDL-C, TG, and limited greater reduction in non–HDL-C (5%; P 5 .024). Likewise, low baseline LDL-C (102 6 23 mg/dL) may have also prohibited significant changes in LDL-C and limited further reduction in non–HDL-C. Furthermore, the self-reported dietary and exercise data might have led to biased assessments. Additionally, the daily quantity of consumed almonds for this study (100 g) may be more than most people can sustain chronically. In the future, a poststudy survey of the almond’s palatability could help determine if subjects could sustain consuming 100 g of almonds daily for longer than 4 weeks. However, we speculate that a smaller daily quantity of almonds for a longer duration may produce comparable or greater lipid effects.
Conclusions The results of this study demonstrate that almonds significantly lower non–HDL-C with notable trends in lowering LDL-C, TG, and VLDL-C without causing significant weight gain in subjects on statin therapy. Similar to other almond studies, this study did not demonstrate significant changes in HDL-C or Lp(a). The significant reduction in non–HDL-C, trends in reduction of other lipoproteins, and the LDL-C particle shift warrant further investigation of almond supplementation in a population taking statin therapy.
Acknowledgment The study was supported by funding from the Almond Board of California and the University of Kansas General Research Fund allocation #2301124. Authors thank Dr. Karen Lapsley, Chief Scientific Officer for the Almond Board of California for her editorial support.
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64 23. Hyson DA, Schneeman BO, Davis PA. Almonds and almond oil have similar effects on plasma lipids and LDL oxidation in healthy men and women. J Nutr. 2002;132:703–707. 24. Jalali-Khanabadi BA, Mozaffari-Khosravi H, Parsaeyan N. Effects of almond dietary supplementation on coronary heart disease lipid risk factors and serum lipid oxidation parameters in men with mild hyperlipidemia. J Altern Complement Med. 2010;16: 1279–1283. 25. Jambazian PR, Haddad E, Rajaram S, Tanzman J, Sabate J. Almonds in the diet simultaneously improve plasma alpha-tocopherol concentrations and reduce plasma lipids. J Am Diet Assoc. 2005;105: 449–454. 26. Phung OJ, Makanji SS, White CM, Coleman CI. Almonds have a neutral effect on serum lipid profiles: a meta-analysis of randomized trials. J Am Diet Assoc. 2009;109:865–873. 27. Taylor AJ, Villines TC, Stanek EJ, et al. Extended-release niacin or ezetimibe and carotid intima-media thickness. N Engl J Med. 2009; 361:2113–2122. 28. Teramoto T, Shimano H, Yokote K, Urashima M. Effects of pitavastatin (LIVALO Tablet) on high density lipoprotein cholesterol (HDL-C) in hypercholesterolemia. J Atheroscler Thromb. 2009;16: 654–661.
Journal of Clinical Lipidology, Vol 9, No 1, February 2015 29. Parlesak A, Eckoldt J, Winkler K, Bode CJ, Schafer C. Intercorrelations of lipoprotein subfractions and their covariation with lifestyle factors in healthy men. J Clin Biochem Nutr. 2014;54:174–180. 30. Lamarche B, Desroches S, Jenkins DJ, 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;92:657–663. 31. El Harchaoui K, van der Steeg WA, Stroes ES, et al. Value of lowdensity lipoprotein particle number and size as predictors of coronary artery disease in apparently healthy men and women: the EPICNorfolk Prospective Population Study. J Am Coll Cardiol. 2007;49: 547–553. 32. Prado KB, Shugg S, Backstrand JR. Low-density lipoprotein particle number predicts coronary artery calcification in asymptomatic adults at intermediate risk of cardiovascular disease. J Clin Lipidol. 2011; 5:408–413. 33. Mora S, Otvos JD, Rifai N, Rosenson RS, Buring JE, Ridker PM. Lipoprotein particle profiles by nuclear magnetic resonance compared with standard lipids and apolipoproteins in predicting incident cardiovascular disease in women. Circulation. 2009;119:931–939. 34. Davidson MH, Ballantyne CM, Jacobson TA, et al. Clinical utility of inflammatory markers and advanced lipoprotein testing: advice from an expert panel of lipid specialists. J Clin Lipidol. 2011;5:338–367.
Statins and almonds to lower lipoproteins (the STALL Study) Janelle F. Ruisinger, PharmD*, Cheryl A. Gibson, PhD, James M. Backes, PharmD, Bryan K. Smith, PhD, CSCS, Debra K. Sullivan, PhD, RD, Patrick M. Moriarty, MD, Penny Kris-Etherton, PhD, RD Department of Pharmacy Practice, University of Kansas School of Pharmacy, Kansas City, KS, USA (Drs Ruisinger and Backes); Department of Internal Medicine, Division of General and Geriatric Medicine, University of Kansas Medical Center, Kansas City, KS, USA (Dr Gibson); Department of Kinesiology and Health Education, Southern Illinois University Edwardsville, Vadalabene Center, Edwardsville, IL, USA (Dr Smith); Department of Dietetics and Nutrition, University of Kansas Medical Center, Kansas City, KS, USA (Dr Sullivan); Department of Medicine, Division of Clinical Pharmacology, University of Kansas Medical Center, Atherosclerosis and LDL–Apheresis Center, Kansas City, KS, USA (Dr Moriarty); and Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA, USA (Dr Kris-Etherton) KEYWORDS: Almonds; Lipoproteins; Nuts; Cholesterol; Statins
BACKGROUND: Dietary supplementation with almonds has demonstrated dose-dependent decreases in low-density lipoprotein cholesterol (LDL-C), likely because of their composition of beneficial nutrients including mono- and polyunsaturated fatty acids, fiber, and protein. OBJECTIVE: The primary objective of this study was to determine the changes in the lipid profile (LDL-C, high-density lipoprotein cholesterol [HDL-C], triglycerides, total cholesterol, non–HDL-C), LDL-C particle size, and lipoprotein (a) when 100 g of almonds daily were added to background statin therapy for 4 weeks. METHODS: Subjects (N 5 48) receiving a consistent statin dose were randomized to 100 g of almonds daily and to The National Cholesterol Education Program Adult Treatment Panel’s third report Therapeutic Lifestyle Changes Diet counseling (almond group; n 5 22) or solely Adult Treatment Panel’s third report Therapeutic Lifestyle Changes Diet counseling (non-almond group; n 5 26), for 4 weeks. RESULTS: No significant changes in weight and weekly physical activity were noted between the 2 groups from baseline. However, the almond group consumed significantly more calories at 4 weeks compared with controls. The almond group experienced a 4.9% reduction in non–HDL-C compared with a 3.5% increase for the non-almond group (P 5 .02). Additionally, notable improvements were observed in LDL-C and triglycerides, but did not achieve statistical significance (P 5 .068 for both parameters). There was also a shift from LDL pattern A to pattern B particles (P 5 .003) in the almond group. No significant differences in total cholesterol (P 5 .1), HDL-C (P 5 .3), or lipoprotein (a) (P 5 .1) were observed. CONCLUSION: Adding 100 g of almonds daily to chronic statin therapy for 4 weeks significantly reduced non–HDL-C. Trial registration: clinicaltrials.gov Identifier: NCT00603876. Ó 2015 National Lipid Association. All rights reserved.
* Corresponding author. J3901 Rainbow Blvd, Mail Stop 4047, Kansas City, KS 66160.
E-mail address: [email protected] Submitted July 1, 2014. Accepted for publication October 2, 2014.
1933-2874/$ - see front matter Ó 2015 National Lipid Association. All rights reserved. http://dx.doi.org/10.1016/j.jacl.2014.10.001
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Introduction Coronary heart disease (CHD) continues to be the leading cause of morbidity and mortality in the United States, affecting an estimated 16.3 million individuals $20 years old or approximately 7% of the total population.1 Elevated low-density lipoprotein cholesterol (LDL-C) is a major modifiable risk factor for CHD. The National Cholesterol Education Program Adult Treatment Panel’s third report (ATP-III), the National Lipid Association (NLA) Recommendations for Patient-centered Management of Dyslipidemia: Part 1 – Executive Summary, and the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the ACC/AHA Task Force on Practice Guidelines, all focus on evidence demonstrating the importance of LDL-C reduction to decrease CHD risk.2–4 Furthermore, ATP-III identifies non–high-density lipoprotein cholesterol (non-HDL-C) as a secondary target in patients with triglycerides (TG) $200 mg/dL, whereas the NLA classifies non–HDL-C as a primary target to reduce CHD risk.2,3 Additionally, the ATP-III guidelines consider lipoprotein(a) [Lp(a)] as an emerging risk factor that has been linked to CHD risk.2 In addition to focusing on lipid biomarkers, ATP-III also emphasizes a healthy diet and regular exercise for patients regardless of LDL-C to decrease their risk for CHD.2 This healthy lifestyle is also supported by the more recent NLA Recommendations and the ACC/AHA Guideline on Lifestyle Management to Reduce Cardiovascular Risk.3,5 Therapeutic Lifestyle Changes (TLC) described in ATP-III advocate a comprehensive lifestyle approach to CHD risk reduction.2 In addition to weight reduction and physical activity, ATP-III promotes the TLC Diet. This approach emphasizes a reduction in saturated fatty acids (,7% of total daily calories) and moderate consumption of unsaturated fats, specifically monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA). Diets considered ‘‘heart healthy’’ (ie, Mediterranean Diet) frequently replace saturated fats with foods high in unsaturated fat such as nuts and olive oil. One hundred grams of almonds contain approximately 32 g of MUFA, 12 g of PUFA, and 4 g of saturated fatty acids.6 Additionally, almonds contain fiber, plant protein, phytochemicals, and sterols, all of which may contribute to their beneficial effects on lipoproteins.7,8 Although almonds are high in unsaturated fats, protein, and fiber, they are also energy-dense (Table 1).6 One hundred grams of almonds contain approximately 579 kcal.6 Thus, patients may risk gaining weight when adding them to their habitual diet. However, studies in general have not found significant increases in weight with varying amounts of almond intake.9–16 It has been proposed that the protein and fiber content of almonds promotes satiety, therefore decreasing caloric intake from other foods and reducing the propensity for weight gain.16,17
59 Table 1
Nutrient profile of almonds
Nutrient
Amount/100 g
Energy (kcal) Protein (g) Total fat (g) Saturated fatty acids (g) Monounsaturated fatty acids (g) Polyunsaturated fatty acids (g) Carbohydrate (g) Fiber (g) Sugars (g)
579 21.2 49.9 3.8 31.5 12.3 21.6 12.5 4.4
For most patients, statins are the cornerstone for LDL-C reduction. However, because of aggressive LDL-C treatment goals, cost, and dose-dependent side effects associated with statins, additional therapy may be required to achieve optimal LDL-C levels. One option that may further reduce LDL-C levels when added to statin therapy is incorporating almonds in a heart-healthy diet. Almonds induce a dose-dependent LDL-C lowering when consumption is .50 g daily.8 To our knowledge, no study has assessed the lipid-lowering effects of almonds when added to statin therapy. Although 1 study by Jenkins et al, included 2 patients on statin therapy in their assessment of almonds in hyperlipidemic patients, the small sample size precludes definitive conclusions.9 We hypothesized that consumption of 100 g of almonds daily would significantly and favorably affect LDL-C, HDL-C, TG, total cholesterol (TC), non–HDL-C, LDL-C particle size, and Lp(a) when added to chronic statin therapy.
Methods Subjects aged 18 to 78 years taking chronic statin therapy, defined as a consistent statin dose for at least 8 weeks before study entry with continuation of the same dose during the 4-week study period, were eligible. Exclusion criteria included: LDL-C levels ,70 mg/dL, the use of lipid-lowering agents other than statins, adherence to specialized diets, nut consumption greater than twice weekly, nut allergies, liver disease, chronic renal or CHD, and alcohol or illicit drug dependence. Postmenopausal women were allowed study entry if not taking hormone replacement therapy or on a consistent hormone replacement therapy dose. Females of child-bearing potential using an effective form of contraception were allowed to participate. Subjects meeting eligibility criteria were randomized to 100 g of almonds daily and ATP-III TLC Diet counseling (almond group) or solely ATP-III TLC Diet counseling (non-almond group). The University of Kansas Medical Center Human Subjects Committee, which serves as the institutional review board, approved the study, and all subjects signed informed consent before study enrollment. This study was registered at Clinicaltrials.gov as NCT00603876.
60 Fasting plasma concentrations of LDL-C, HDL-C, TG, very LDL-C (VLDL-C), and Lp(a) were directly measured by Atherotech Diagnostics Lab using the inverted rate zonal, single verticle spin, ultra-centrifugation based Vertical Auto Profile method.18 This was a single-site, 2-arm pilot study comparing the effects of almond consumption for 4 weeks (after a 1-week screening period) to no almond consumption. All subjects were instructed to maintain their current diet during the screening period (week 0) and complete a 3-day food record. At week 1, subjects returned for their second visit, which included randomization, fasting lipid panel, LDL-C particle size, Lp(a) measurements, and biometric measurements (blood pressure, weight, height, and waist circumference). Also during week 1, all subjects received ATP-III TLC Diet counseling via telephone from a registered dietitian who reviewed their initial 3-day food record. Subjects randomized to treatment received further instruction on how to compensate for the added calories from the almonds. Whole California almonds were supplied as raw and unsalted in preweighed 100 g individual packages. Food intake was again recorded (via 3-day food record) by the subjects at weeks 2 and 4. For each of the 3 food records, subjects were required to document all food and drink consumed for 3 consecutive days including 1 weekend day. Dietary intake data were collected and analyzed using Nutrition Data System for Research software, version 2010, developed by the Nutrition Coordinating Center, University of Minnesota, Minneapolis, MN. Adherence was assessed at week 4 by counting unconsumed packages of almonds. Physical activity for each subject was also assessed at screening (week 0) and week 4 using the Physical Activity Questionnaire.19 Subjects were instructed to maintain their current activity level and exercise routines during the study period. To compare mean values, t-tests were used to determine statistical significance between treatments. Analysis of variance, Fisher’s exact, and Pearson chi-square tests, as appropriate, were employed to assess differences in characteristics of subjects, such as LDL subclass patterns A and B. Statistical significance was accepted at P , .05. Statistical analyses were performed with the SPSS PC1 (Statistical Package for the Social Sciences) software (SPSS version 14, Chicago, IL).
Results Fifty subjects were enrolled, and 22 subjects in the almond group and 26 subjects in the non-almond group completed the study. Two subjects in the almond group withdrew because of the inability to consume the almonds daily and concerns about the additional energy intake. Of those who completed the study, the mean age was about 60 years and 50% were female. Baseline characteristics did not differ between the 2 groups (Table 2). Adherence to almond consumption was .95%.
Journal of Clinical Lipidology, Vol 9, No 1, February 2015 Table 2 Baseline characteristics for all subjects completing the study*
Variables
ATP-III TLC Diet counseling 1 almonds
Age (y) 60.0 6 10.4 Gender Female 10 Male 12 Weight (lb) 191.3 6 29.4 BMI (kg/m2) 29.8 6 4.8 Waist circumference (in) 39.9 6 4.9 Blood pressure (mm/Hg) Systolic 123 6 16 Diastolic 79 6 8 Chronic conditions Hypertension 9 Type 2 diabetes 1 mellitus Mean daily statin dose (mg) Atorvastatin 16.7 (n 5 3) Lovastatin 40 (n 5 2) Pravastatin 40 (n 5 1) Rosuvastatin 20 (n 5 2) Simvastatin 30 (n 5 14) Plasma lipids (mg/dL) Total cholesterol 171.4 6 27.1 LDL-C 101.0 6 22.0 HDL-C 51.9 6 13.6 Triglycerides 102.8 6 37.7 Non-HDL 119.3 6 23.2 Lp(a) 7.8 6 3.3 IDL 8.9 6 5.6 Energy consumed 1729 6 429 (kcal/day) Physical activity 1341 6 1675 (kcal/wk)
ATP-III TLC Diet counseling 59.3 6 11.7 14 12 179.2 6 31.5 28.6 6 3.9 37.6 6 4.5 119 6 14 77 6 10 12 3
22 (n 5 5) 20 (n 5 1) 33.3 (n 5 3) 7.5 (n 5 2) 36.7 (n 5 15) 175.4 102.5 54.7 103.4 120.5 9.0 10.3 1820
6 6 6 6 6 6 6 6
30.6 24.5 14.1 49.7 27.2 6.5 6.9 585
1813 6 1365
ATP-III TLC, Adult Treatment Panel’s third report Therapeutic Lifestyle Changes; BMI, body mass index; HDL-C, high-density lipoprotein cholesterol; IDL, intermediate-density lipoprotein; LDL-C, low-density lipoprotein cholesterol; Lp(a), lipoprotein(a). Data are expressed as mean 6 standard deviation. *No differences noted between groups.
At study close, there were no significant differences in weight, body mass index, or physical activity between the 2 study groups (Table 3). A significant difference between the almond group and non-almond groups was found in non– HDL-C with a 4.9% decrease among the almond group from baseline compared with a 3.5% increase for the non-almond group (P 5 .024). The almond group had notable improvements in LDL-C and TG, but these did not achieve statistical significance (P 5 .068 and .068, respectively) (Table 3). The change in VLDL was statistically significant (P 5 .01), with the VLDL levels among the non-almond group increasing 12.7%, whereas the levels in the almond group decreased by 3.3%. The almonds also significantly affected LDL pattern type, which resulted in a
Ruisinger et al Table 3
The STALL Study
61
Changes in body weight, lipoprotein parameters, and calories burned from baseline to 4 weeks
Parameter
Week
ATP-III TLC Diet counseling 1 almonds
Weight (lb)
0 4 0 4
191.3 192.1 29.8 30.0
6 6 6 6
29.4 29.2 4.8 4.8
179.2 179.0 28.6 28.5
6 6 6 6
31.5 32.0 3.9 4.0
0 4 0 4 0 4 0 4 0 4 0 4 0 4 0 4
171.4 165.6 101.0 95.6 51.9 52.2 102.8 102.1 18.4 17.8 119.3 113.4 7.8 7.5 8.9 7.8
6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6
27.1 31.3 22.0 23.9 13.6 13.8 37.7 38.3 3.7 4.0 23.2 24.5 3.3 3.7 5.6 5.5
175.4 177.2 102.5 104.3 54.7 52.4 103.4 115.0 18.1 20.4 120.5 124.7 9.0 8.9 10.3 12.0
6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6
30.7 23.7 24.5 18.7 14.1 11.0 49.7 42.6 5.7 5.1 27.2 20.8 6.5 6.1 6.9 4.5
0 4 0 4 0 4 0 4
13 9 7 7 2 6 1341 6 1675 1481 6 2246
BMI (kg/m2) Lipids (mg/dL) TC LDL-C HDL-C Triglycerides VLDL-C Non-HDL-C Lp(a) IDL-C Pattern (n, %) A AB B Physical activity (kcal/week)
ATP-III TLC Diet counseling
18 18 4 4 4 4 1813 6 1365 1674 6 1265
P value .145 .262
.102 .068 .347 .068 .01* .024 .109 .004
.003† .311
ATP-III TLC, Adult Treatment Panel’s third report Therapeutic Lifestyle Changes; BMI, body mass index; HDL-C, high-density lipoprotein cholesterol; IDL-C, intermediate-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; Lp(a), lipoprotein(a); TC, total cholesterol; VLDL, very low-density lipoprotein cholesterol. Data are expressed as mean 6 standard deviation. *The change in VLDL-C is significant for the non-almond group only. †The change in distribution of pattern type is significant for the almond group only.
shift from pattern A to pattern B (P 5 .003). There were no differences in TC, HDL-C, or Lp(a) between the 2 groups from baseline (Table 3). Subjects in the almond group reported overall higher daily energy intake as well as overall higher daily intake of total fat, saturated fat, MUFA, PUFA, total protein, vegetable protein, and insoluble fiber at end of study compared with controls (P , .05) (Table 4).
Discussion The results of this study demonstrate that adding 100 g of almonds daily can significantly lower non–HDL-C in subjects on statin therapy and elicit beneficial trends in other lipoprotein parameters. Compared with LDL-C, our findings suggest that non–HDL-C more consistently predicts coronary events.20 Therefore, consistent almond consumption could be used as a strategy to lower non– HDL-C and further reduce CHD risk for patients on statin
therapy. Additionally, adding almonds may be especially appealing to patients unwilling or unable to take higher statin doses. Body weight did not increase significantly during 4 weeks of consuming 100 g of almonds daily, despite higher daily energy intake. This is consistent with data from Spiller et al, who also demonstrated in 2 separate studies that 100 g of almonds daily for 4 weeks did not appreciably affect weight.10,11 In contrast, another study evaluating 2 oz of almonds (w57 g) daily for 6 months in 81 subjects caused statistically significant weight gain (1.43 pounds) in men but not women.21 The authors concluded this weight gain was slight and likely biologically insignificant. Furthermore, another study observed statistically significant weight gain in 20 healthy subjects consuming 100 g of almonds daily for 4 weeks.22 Similar to our study, however, several other studies have shown that diet supplementation with varying amounts of almonds does not significantly affect body weight.9–16 It is likely that,
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Journal of Clinical Lipidology, Vol 9, No 1, February 2015
Table 4 Changes in caloric intake and select nutrients for almond and non-almond groups from baseline to 4 weeks
Item Energy intake (kcal/day) Total fat (g/d) Total protein (g/d)
ATP-III TLC Diet ATP-III counseling 1 TLC Diet counseling Week almonds
P value
0
1729 6 429
1820 6 585 NS
4 0 4 0
2031 6 477 74 111 79
1771 6 521 .003* 70 NS 60 .00 79 NS
4 0
90 24
73 24
.01 NS
4 0 4 0 4 0
25 28 53 16 24 12
20 26 23 16 13 16
.05 NS .00 NS .00 NS
4 Vegetable 0 protein (g/d) 4
20 23
16 28
.04 NS
39
27
.00
Saturated fat (g/d) MUFA (g/d) PUFA (g/d) Insoluble fiber (g/d)
ATP-III TLC, Adult Treatment Panel’s third report Therapeutic Lifestyle Changes; MUFA, monounsaturated fatty acids; NS, not significant; PUFA, polyunsaturated fatty acids. Energy intake expressed as mean 6 standard deviation. *Change in energy intake is significant for the almond group only.
although almonds are energy-dense, the protein, unsaturated fat, and fiber content cause satiation, preventing the subjects from consuming additional calories. However, it is still important that patients consume almonds in place of other calorie sources and not simply add them to habitual caloric intake. Moreover, because the energy content of almonds was recently shown to be significantly less than the energy density as determined using the Atwater factor, it is likely that subjects absorbed fewer calories from the ingested almonds than would be expected.17 Our study also demonstrated that adding almonds to statin therapy produced favorable trends in LDL-C and TG. Several other studies have shown significant decreases in LDL-C with the addition of varying amounts of almonds,9–11,13,14,22–25 and a meta-analysis by Phung et al reported that almonds strongly trend toward significantly lowering LDL-C.26 However, to our knowledge, none of these studies focused on subjects already taking statin therapy. In addition, subjects in the present study had a mean baseline LDL-C of 102 6 23 mg/dL. Two separate studies by Spiller et al using 100 g of almonds daily for 4 weeks demonstrated a significant reduction in LDL-C, but subjects had a baseline LDL-C of 166 6 26 mg/dL and 156 6 28 mg/dL, respectively.10,11 Our data showed a trend
toward LDL-C lowering, but the lack of statistical significance is likely a consequence of low baseline LDL-C resulting from the concurrent statin therapy. Similar to other almond studies, our study was 4 weeks in duration. However, it is possible that extending the study period would produce greater lipoprotein reductions. Hyson et al demonstrated that subjects consuming 66 6 5 g of almonds daily for 6 weeks produced a statistically significant 6% and 14% reduction in LDL-C and TG, respectively.23 We speculate that a smaller daily quantity of almonds for a longer duration may produce comparable or greater lipoprotein effects. Additionally, consuming almonds for a longer duration may produce significant changes in HDL-C. As previous studies suggest, other therapies require a longer duration to observe improvements in HDL-C.27,28 Most studies have shown that almonds do not affect TG. However, 1 study demonstrated that approximately 66 g of almonds daily significantly decreased TG.23 The nonsignificant TG and VLDL-C reductions in our study contributed to the significant reduction in non–HDL-C. These differing results may reflect the high overall variability of TGs, as observed in studies and clinical practice. Additionally, subjects in our study did not experience a change in Lp(a). In contrast, 1 study (n 5 27) showed a significant 7.8% reduction in Lp(a) with 73 g of almonds daily for 4 weeks.9 However, similar to our study, Damasceno et al showed no effect on Lp(a) in 18 subjects consuming 50 to 75 g of almonds for 4 weeks, nor did Jalali-Khanabadi et al in 30 subjects consuming 60 g of almonds daily for 4 weeks.13,24 This study demonstrated a statistically significant shift from pattern A (larger, buoyant LDL-C particles) to pattern B (smaller, dense LDL-C particles) (P 5 .003). This is an unexpected finding because several studies, including a recent study by Parlesak et al, demonstrated decreased small, dense LDL-C levels with increased MUFA consumption.29 Our subjects in the almond group consumed significantly more MUFA compared with the non-almond group (Table 4). However, a study by Lamarche et al30 demonstrated that a diet including plant sterols, viscous fiber, soybean protein, and almonds did not significantly affect LDL-C particle size, but suggested a shift from large LDL-C particles to smaller LDL-C particles. Although the clinical significance of LDL-C particle size is emerging, a growing evidence base suggests that smaller LDL-C particles are associated with higher CHD risk.31–33 However, a panel of lipid experts concluded in a 2011 publication that ‘‘there is no evidence that a shift in LDL subfractions directly translates into change in disease progression or improved outcome.’’34 The LDL-C particle size shift realized in the almond group is an unexpected finding that warrants further investigation.
Strengths Strengths to this study include subjects’ high adherence to consuming the almonds (.95%). In the future, it would be interesting to assess if adherence to almonds for
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lowering lipoproteins is higher than that of statins because the adherence to statin therapy is often low. A second strength is the low dropout rate. Only two subjects withdrew from the study because of an inability to consume almonds daily. All other subjects completed the study.
Limitations Limitations to this study include the relatively small sample size (n 5 48), which may have precluded detection of significant changes in LDL-C, TG, and limited greater reduction in non–HDL-C (5%; P 5 .024). Likewise, low baseline LDL-C (102 6 23 mg/dL) may have also prohibited significant changes in LDL-C and limited further reduction in non–HDL-C. Furthermore, the self-reported dietary and exercise data might have led to biased assessments. Additionally, the daily quantity of consumed almonds for this study (100 g) may be more than most people can sustain chronically. In the future, a poststudy survey of the almond’s palatability could help determine if subjects could sustain consuming 100 g of almonds daily for longer than 4 weeks. However, we speculate that a smaller daily quantity of almonds for a longer duration may produce comparable or greater lipid effects.
Conclusions The results of this study demonstrate that almonds significantly lower non–HDL-C with notable trends in lowering LDL-C, TG, and VLDL-C without causing significant weight gain in subjects on statin therapy. Similar to other almond studies, this study did not demonstrate significant changes in HDL-C or Lp(a). The significant reduction in non–HDL-C, trends in reduction of other lipoproteins, and the LDL-C particle shift warrant further investigation of almond supplementation in a population taking statin therapy.
Acknowledgment The study was supported by funding from the Almond Board of California and the University of Kansas General Research Fund allocation #2301124. Authors thank Dr. Karen Lapsley, Chief Scientific Officer for the Almond Board of California for her editorial support.
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