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Whole-diet interventions and cardiovascular risk factors in postmenopausal women: A systematic review of controlled clinical trials

Open AccessPublished:October 09, 2021DOI:https://doi.org/10.1016/j.maturitas.2021.10.001

      Highlights

      • This systematic review summarizes current evidence about the effects of whole-diet interventions on cardiovascular risk factors among postmenopausal women.
      • Due to the large heterogeneity in intervention diets, comparison groups, intervention durations, and population characteristics in the limited number of studies that are currently available, overall findings are inconclusive.
      • Fat-modified diets are the most studied dietary interventions, and may improve concentrations of total and low-density lipoprotein cholesterol, systolic blood pressure, fasting blood sugar, and apolipoprotein A in comparison with the control diets.
      • Some adverse effects of fat-modified diets on other lipid profile markers and insignificant effects on glycemic indices and blood pressure were also observed.
      • Further well-designed clinical trials to find optimal diets for cardiovascular disease prevention in postmenopausal women are urgently needed.

      Abstract

      Objectives

      Menopause is accompanied by many metabolic changes, increasing the risk of cardiometabolic diseases. The impact of diet, as a modifiable lifestyle factor, on cardiovascular health in general populations has been well established. The purpose of this systematic review is to summarize the evidence on the effects of whole diet on lipid profile, glycemic indices, and blood pressure in postmenopausal women.

      Methods

      Embase, Medline, Cochrane Central Register of Controlled Trials, and Google Scholar were searched from inception to February 2021. We included controlled clinical trials in postmenopausal women that assessed the effect of a whole-diet intervention on lipid profile, glycemic indices, and/or blood pressure. The risk of bias in individual studies was assessed using RoB 2 and ROBINS-I tools.

      Summary of evidence

      Among 2,134 references, 21 trials met all eligibility criteria. Overall, results were heterogenuous and inconsistent. Compared to control diets, some studies showed that participants experienced improvements in total cholesterol (TC), low-density lipoprotein cholesterol (LDL), systolic blood pressure (SBP), fasting blood sugar (FBS), and apolipoprotein A (Apo-A) after following fat-modified diets, but some adverse effects on triglycerides (TG), very low-density lipoprotein cholesterol (VLDL), lipoprotein(a) (Lp(a)), and high-density lipoprotein cholesterol (HDL) concentrations were also observed. A limited number of trials found some effects of the Paleolithic, weight-loss, plant-based, or energy-restricted diets, or of following American Heart Association recommendations on TG, TC, HDL, insulin, FBS, or insulin resistance.

      Conclusion

      Current evidence suggests that diet may affect levels of some lipid profile markers, glycemic indices, and blood pressure among postmenopausal women. However, due to the large heterogeneity in intervention diets, comparison groups, intervention durations, and population characteristics, findings are inconclusive. Further well-designed clinical trials are needed on dietary interventions to reduce cardiovascular risk in postmenopausal women.

      Keywords

      1. Introduction

      Menopause is reflected by reduced secretion of progesterone and estrogen hormones [
      • Nelson HD.
      ]. Reduced estrogen may result in unfavorable weight gain, changes in body fat distribution, reduced glucose tolerance, and adverse changes in lipoprotein pattern [2–4]. The cumulative effect of these changes might explain the consistently observed adverse associations between menopause and metabolic syndrome, independent of age [
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      The emergence of the metabolic syndrome with menopause.
      ], resulting in increased risk of cardiovascular, osteoarthritis, diabetes, cancers, and chronic kidney diseases [
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      Bone Health During the Menopause Transition and Beyond.
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      ]. Although menopause is a part of women life and its subsequent symptoms could affect their quality of life, this topic has only recently gained momentum in the scientific literature.
      Dietary intervention is widely considered to be one of the most important modifiable lifestyle factors as primary prevention for cardiovascular events in the general population [
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      Cardiovascular Disease Prevention by Diet Modification: JACC Health Promotion Series.
      ]. In women, it has been suggested that the dietary intakes are also associated with menopausal symptoms severity, although the findings are inconsistent and inconclusive [
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      ].
      So far, the majority of studies have investigated the effects of supplements, nutrients, or isolated single foods on menopausal health issues in postmenopausal women [
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      ,

      Patade A, Devareddy L, Lucas EA, Korlagunta K, Daggy BP, Arjmandi BH. Flaxseed reduces total and LDL cholesterol concentrations in Native American postmenopausal women. Journal of women's health (2002). 2008;17(3):355-66.

      ,
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      ] and fewer studies have paid attention to the impact of a whole diet on cardiovascular risk factors in this population. In this regard, several controlled clinical trials with various intervention diets and different findings on cardiovascular risk factors were published. For example, findings of Women's Health Initiative Dietary Modification Trial (WHI-DM), designed to assess the effects of a low-fat dietary pattern during 6 years in comparison with dietary guidelines for Americans, showed no considerable differences between intervention and control groups on cardiovascular risk factors [
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      ]. A parallel comparison between a healthy diet and habitual dietary intakes showed decreases in fasting blood sugar (FBS), total cholesterol (TC), and triglyceride (TG) levels in intervention group without any considerable differences compared to the control group [
      • Abedi P
      • Huang Soo Lee M
      • Yasin Z
      • Kandiah M
      Diet intervention to improve cardiovascular risk factors among iranian postmenopausal women.
      ]. On the other hand, a diet providing less than 30 % of energy from fats could considerably improve FBS, insulin, and insulin sensitivity in comparison with habitual dietary intakes [
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      ]. Also, a meta-analysis of clinical trials, published in 2014, observed no considerable effects following a low-fat diet intake on lipid markers in postmenopausal women [
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      ].
      There is a lack of consensus regarding an optimal diet for improving cardiometabolic health in postmenopausal women. Although previous reviews focused on of the role of supplements or single food components, the impacts of a whole diet on cardiovascular risk factors in this population have been scarcely investigated. Thus, the purpose of this systematic review is to summarize current evidence from controlled clinical trials on the effects of dietary interventions on lipid profile, glycemic indices, and blood pressure in postmenopausal women. This knowledge could assist further research in dietary intervention studies and inform the development of dietary guidelines specifically for postmenopausal women.

      2. Methods

      2.1 Review Design

      The current systematic review was conducted and reported based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [
      • Liberati A
      • Altman DG
      • Tetzlaff J
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      • Liberati A
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      • Altman DG
      • Group P.
      Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
      ]. The protocol of this review was registered in PROSPERO (CRD42021242980).

      2.2 Data Sources and Search Strategy

      A systematic search in Embase, Medline, Cochrane Central Register of Controlled Trials, and Google Scholar was performed to identify controlled clinical trials examining the effects of the whole diet compared to other diets, habitual diets, or general recommendations on lipid profile, glycemic indices, and blood pressure in postmenopausal women irrespective of health status, from inception to February 2021. Related key terms to post-menopause, diet, lipid profile, glycemic indices, blood pressure, and clinical trials were used to build the search strategy. More information on PICO details and search strategy is provided in the Supplementary Tables 1 and 2. A librarian expert (WMB) was involved in developing the search strategy. Additionally, the reference lists of the eligible studies were screened to identify relevant articles.

      2.3 Inclusion and Exclusion Criteria

      Studies were included if they met the following criteria: 1) were randomized or non-randomized controlled clinical trials; 2) designed to assess the effects of a whole diet (e.g. low-fat, plant-based, low/high-carbohydrates diets); 3) conducted only in post-menopausal women irrespective of health or disease status (in both intervention and control groups); 4) reported at least one of the following outcomes: total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL), non-HDL, low-density lipoprotein cholesterol (LDL), very low-density lipoprotein cholesterol (VLDL), lipoprotein (a) (Lp(a)), apolipoprotein A and B (Apo A and Apo B), FBS, Insulin, Hemoglobin A1C (HbA1C), insulin sensitivity and resistance indices (Homeostatic Model Assessment for Insulin Resistance (HOMA), quantitative insulin sensitivity check index (QUICKI)), systolic blood pressure (SBP), or diastolic blood pressure (DBP); 5) published in English.
      We excluded all studies that 1) were uncontrolled clinical trials, observational, editorials, reviews, or conference abstracts; 2) were designed to assess the impacts of only specific food components, nutrients, supplements, or combined interventions (e.g. combination of diet and physical activity/exercise, stress management, smoking cessation); 3) were conducted in men or women other than post-menopausal women.

      2.4 Study Selection and Data Extraction

      Studies were selected in duplicate by independent researchers (MA, IK, AVW, AV, ML) in two steps. In the first step, the titles/abstracts of the identified articles were screened according to the eligibility criteria. Afterward, the full-texts of the included articles from the previous step were screened to identify the final number of eligible studies. Five researchers (MA, IK, AVW, AV, SB) extracted the following data from each study: 1) general information (first author, publication year, country); 2) trial characteristics (design, sample size, intervention duration, intervention/control details, feeding/nonfeeding, isocaloric or not); 3) participants’ characteristics (health status and age); 4) summary of results regarding the mentioned lipid profile markers, glycemic indices, and blood pressure, and any adjustments. On condition that multiple articles reporting on the same outcomes from the same study, the information of the article reporting the most complete groups of outcomes was extracted. In the case of several intervention durations, findings of the longest period were extracted. Any lack of consensus about study selection or data extraction was adjudicated by a discussion with the principal investigator (TV).

      2.5 Quality Assessment

      The quality of the included trials was assessed using Cochrane tool for assessing risk of bias in randomized trials (RoB 2 tool) [
      • Sterne JAC
      • Savović J
      • Page MJ
      • Elbers RG
      • Blencowe NS
      • Boutron I
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      RoB 2: a revised tool for assessing risk of bias in randomised trials.
      ] and Risk Of Bias In Non-randomized Studies of Intervention (ROBINS-I) [
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      ]. RoB 2 tool estimates the risk of bias based on five domains, including 1) randomization process; 2) deviations from intended interventions; 3) missing outcome data; 4) measurement of the outcome; 5) selection of the reported result. ROBINS-I assesses the quality of the studies in specific domains in three levels, pre-intervention (bias due to confounding and selection of participants), at intervention (bias in classification of interventions), and post-intervention (bias due to deviations from intended interventions, missing data, measurement of outcomes, selection of the reported result). Two investigators (SB and MA) performed the quality assessments and disagreements were resolved by discussion.

      3. Results

      3.1 Search Outcome

      Our search strategy yielded 2,134 references. Ninety-one articles were included after titles/abstracts screening. Full-texts screening resulted in exclusion of 63 articles, of which ten studies were conference abstracts [
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      Adherence to a high protein and low fat energy-restricted diet while participating in a circuit resistance-exercise program promotes positive changes in blood glucose and lipids in postmenopausal women.
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      ], eight were conducted in populations other than post-menopausal women [

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      ], and twenty-two were excluded since they were derived from the same projects and/or did not report relevant outcomes [
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      • Hassager C
      • Christiansen C.
      Leptin in overweight postmenopausal women: No relationship with metabolic syndrome X or effect of exercise in addition to diet.
      ,
      • Colombo C
      • Muti P
      • Pala V
      • Cavalleri A
      • Venturelli E
      • Locardi M
      • et al.
      Plant-based diet, serum fatty acid profile, and free radicals in postmenopausal women: The diet and androgens (DIANA) randomized trial.
      ,
      • Foster-Schubert K
      • Campbell K
      • Kratz M
      • Makar KW
      • Hagman D
      • Schur EA
      • et al.
      Gene-expression changes in adipose tissue with diet-and/or exercise-induced weight loss: a randomized controlled trial.
      ,
      • Franklin KA
      • Eriksson M
      • Larsson C
      • Lindahl B
      • Mellberg C
      • Sahlin C
      • et al.
      Palaeolithic diet and obstructive sleep apnoea in overweight females: a randomised controlled trial.
      ,
      • Howard BV
      • Van Horn L
      • Hsia J
      • Manson JE
      • Stefanick ML
      • Wassertheil-Smoller S
      • et al.
      Low-fat dietary pattern and risk of cardiovascular disease: The Women's Health Initiative randomized controlled dietary modification trial.
      ,
      • Raatz SK
      • Young LR
      • Picklo MJ
      • Sauter ER
      • Qin W
      • Kurzer MS.
      Total dietary fat and fatty acid content modifies plasma phospholipid fatty acids, desaturase activity indices, and urinary prostaglandin E in women.
      ]. Also, one full-text, published in 1987, could not be retrieved [
      • Ingram DM
      • Bennett FC
      • Willcox D
      • De Klerk N.
      Effect of low-fat diet on female sex hormone levels.
      ]. Eventually, 27 articles, reporting on 21 unique trials, were included in the current systematic review [
      • Howard BV
      • Curb JD
      • Eaton CB
      • Kooperberg C
      • Ockene J
      • Kostis JB
      • et al.
      Low-fat dietary pattern and lipoprotein risk factors: The Women's Health Initiative Dietary Modification Trial.
      ,
      • Tinker LF
      • Bonds DE
      • Margolis KL
      • Manson JE
      • Howard BV
      • Larson J
      • et al.
      Low-fat dietary pattern and risk of treated diabetes mellitus in postmenopausal women: The women's health initiative randomized controlled dietary modification trial.
      ,
      • Abedi P
      • Huang Soo Lee M
      • Yasin Z
      • Kandiah M
      Diet intervention to improve cardiovascular risk factors among iranian postmenopausal women.
      ,
      • Mason C
      • Foster-Schubert KE
      • Imayama I
      • Kong A
      • Xiao L
      • Bain C
      • et al.
      Dietary weight loss and exercise effects on insulin resistance in postmenopausal women.
      ,

      Bajerska J, Chmurzynska A, Muzsik A. Weight loss and metabolic health effects from energy-restricted Mediterranean and Central-European diets in postmenopausal women: A randomized …: nature.com; 2018.

      ,
      • Barnard ND
      • Scialli AR
      • Turner-McGrievy G
      • Lanou AJ
      • Glass J.
      The effects of a low-fat, plant-based dietary intervention on body weight, metabolism, and insulin sensitivity.
      ,
      • Buzzard IM
      • Asp EH
      • Chlebowski RT
      • Boyar AP
      • Jeffery RW
      • Nixon DW
      • et al.
      Diet intervention methods to reduce fat intake: nutrient and food group composition of self-selected low-fat diets.
      ,
      • Denke MA.
      Individual responsiveness to a cholesterol-lowering diet in postmenopausal women with moderate hypercholesterolemia.
      ,
      • Harrington M
      • Bennett T
      • Jakobsen J
      • Ovesen L
      • Brot C
      • Flynn A
      • et al.
      The effect of a high-protein, high-sodium diet on calcium and bone metabolism in postmenopausal women and its interaction with vitamin D receptor genotype.
      ,
      • Jeppesen J
      • Schaaf P
      • Jones C
      • Zhou MY
      • Ida Chen YD
      • Reaven GM
      Effects of low-fat, high-carbohydrate diets on risk factors for ischemic heart disease in postmenopausal women.
      ,
      • Kasim-Karakas SE
      • Almario RU
      • Mueller WM
      • Peerson J.
      Changes in plasma lipoproteins during low-fat, high-carbohydrate diets: effects of energy intake.
      ,
      • Murillo-Ortiz B
      • Martinez-Garza S
      • Landeros VC
      • Velazquez GC
      • Garcia DS.
      Effect of reduced dietary fat on estradiol, adiponectin, and IGF-1 levels in postmenopausal women with breast cancer.
      ,
      • Nowson CA
      • Wattanapenpaiboon N
      • Pachett A.
      Low-sodium Dietary Approaches to Stop Hypertension-type diet including lean red meat lowers blood pressure in postmenopausal women.
      ,

      Segal-Isaacson CJ, Johnson S, Tomuta V. A randomized trial comparing low-fat and low-carbohydrate diets matched for energy and protein. Obesity …. 2004.

      ,
      • Thomson CA
      • Stopeck AT
      • Bea JW
      • Cussler E
      • Nardi E
      • Frey G
      • et al.
      Changes in body weight and metabolic indexes in overweight breast cancer survivors enrolled in a randomized trial of low-fat vs. reduced carbohydrate diets.
      ,
      • Berrino F
      • Bellati C
      • Secreto G
      • Camerini E
      • Pala V.
      Reducing bioavailable sex hormones through a comprehensive change in diet: the diet and androgens (DIANA) randomized trial.
      ,
      • Muti P
      • Awad AB
      • Schünemann H
      • Fink CS
      • Hovey K
      • Freudenheim JL
      • et al.
      A Plant Food-Based Diet Modifies the Serum β-Sitosterol Concentration in Hyperandrogenic Postmenopausal Women.
      ,
      • Shikany JM
      • Margolis KL
      • Pettinger M
      • Jackson RD
      • Limacher MC
      • Liu S
      • et al.
      Effects of a low-fat dietary intervention on glucose, insulin, and insulin resistance in the Women's Health Initiative (WHI) dietary modification trial.
      ,
      • Bhargava A.
      Fiber intakes and anthropometric measures are predictors of circulating hormone, triglyceride, and cholesterol concentrations in the women's health trial.
      ,
      • Dallas Hall W
      • Feng Z
      • George VA
      • Lewis CE
      • Oberman A
      • Huber M
      • et al.
      Low-fat diet: Effect on athropometrics, blood pressure, glucose, and insulin in older women.
      ,
      • Ginsberg HN
      • Kris-Etherton P
      • Dennis B
      • Elmer PJ
      • Ershow A
      • Lefevre M
      • et al.
      Effects of reducing dietary saturated fatty acids on plasma lipids and lipoproteins in healthy subjects: The delta study, protocol 1.
      ,
      • Mellberg C
      • Sandberg S
      • Ryberg M
      • Eriksson M
      • Brage S
      • Larsson C
      • et al.
      Long-term effects of a Palaeolithic-type diet in obese postmenopausal women: A 2-year randomized trial.
      ,
      • Otten J
      • Mellberg C
      • Ryberg M
      • Sandberg S
      • Kullberg J
      • Lindahl B
      • et al.
      Strong and persistent effect on liver fat with a Paleolithic diet during a two-year intervention.
      ,
      • McColley SP
      • Georgopoulos A
      • Young LR
      • Kurzer MS
      • Redmon JB
      • Raatz SK.
      A high-fat diet and the threonine-encoding allele (Thr54) polymorphism of fatty acid-binding protein 2 reduce plasma triglyceride-rich lipoproteins.
      ,
      • Young LR
      • Kurzer MS
      • Thomas W
      • Redmon JB
      • Raatz SK.
      Low-fat diet with omega-3 fatty acids increases plasma insulin-like growth factor concentration in healthy postmenopausal women.
      ,
      • Sénéchal M
      • Bouchard DR
      • Dionne IJ
      • Brochu M.
      The effects of lifestyle interventions in dynapenic-obese postmenopausal women.
      ,
      • Svendsen OL
      • Hassager C
      • Christiansen C.
      Effect of an energy-restrictive diet, with or without exercise, on lean tissue mass, resting metabolic rate, cardiovascular risk factors, and bone in overweight postmenopausal women.
      ]. Figure 1 represents the study selection procedure.

      3.2 Study Characteristics

      The included studies were published between 1990 and 2018. Studies were conducted in Poland [

      Bajerska J, Chmurzynska A, Muzsik A. Weight loss and metabolic health effects from energy-restricted Mediterranean and Central-European diets in postmenopausal women: A randomized …: nature.com; 2018.

      ], Mexico [
      • Murillo-Ortiz B
      • Martinez-Garza S
      • Landeros VC
      • Velazquez GC
      • Garcia DS.
      Effect of reduced dietary fat on estradiol, adiponectin, and IGF-1 levels in postmenopausal women with breast cancer.
      ], Sweden [
      • Mellberg C
      • Sandberg S
      • Ryberg M
      • Eriksson M
      • Brage S
      • Larsson C
      • et al.
      Long-term effects of a Palaeolithic-type diet in obese postmenopausal women: A 2-year randomized trial.
      ], the United States [
      • Howard BV
      • Curb JD
      • Eaton CB
      • Kooperberg C
      • Ockene J
      • Kostis JB
      • et al.
      Low-fat dietary pattern and lipoprotein risk factors: The Women's Health Initiative Dietary Modification Trial.
      ,
      • Mason C
      • Foster-Schubert KE
      • Imayama I
      • Kong A
      • Xiao L
      • Bain C
      • et al.
      Dietary weight loss and exercise effects on insulin resistance in postmenopausal women.
      ,
      • Barnard ND
      • Scialli AR
      • Turner-McGrievy G
      • Lanou AJ
      • Glass J.
      The effects of a low-fat, plant-based dietary intervention on body weight, metabolism, and insulin sensitivity.
      ,
      • Buzzard IM
      • Asp EH
      • Chlebowski RT
      • Boyar AP
      • Jeffery RW
      • Nixon DW
      • et al.
      Diet intervention methods to reduce fat intake: nutrient and food group composition of self-selected low-fat diets.
      ,
      • Denke MA.
      Individual responsiveness to a cholesterol-lowering diet in postmenopausal women with moderate hypercholesterolemia.
      ,
      • Jeppesen J
      • Schaaf P
      • Jones C
      • Zhou MY
      • Ida Chen YD
      • Reaven GM
      Effects of low-fat, high-carbohydrate diets on risk factors for ischemic heart disease in postmenopausal women.
      ,
      • Kasim-Karakas SE
      • Almario RU
      • Mueller WM
      • Peerson J.
      Changes in plasma lipoproteins during low-fat, high-carbohydrate diets: effects of energy intake.
      ,

      Segal-Isaacson CJ, Johnson S, Tomuta V. A randomized trial comparing low-fat and low-carbohydrate diets matched for energy and protein. Obesity …. 2004.

      ,
      • Thomson CA
      • Stopeck AT
      • Bea JW
      • Cussler E
      • Nardi E
      • Frey G
      • et al.
      Changes in body weight and metabolic indexes in overweight breast cancer survivors enrolled in a randomized trial of low-fat vs. reduced carbohydrate diets.
      ,
      • Ginsberg HN
      • Kris-Etherton P
      • Dennis B
      • Elmer PJ
      • Ershow A
      • Lefevre M
      • et al.
      Effects of reducing dietary saturated fatty acids on plasma lipids and lipoproteins in healthy subjects: The delta study, protocol 1.
      ,
      • Young LR
      • Kurzer MS
      • Thomas W
      • Redmon JB
      • Raatz SK.
      Low-fat diet with omega-3 fatty acids increases plasma insulin-like growth factor concentration in healthy postmenopausal women.
      ], Iran [
      • Abedi P
      • Huang Soo Lee M
      • Yasin Z
      • Kandiah M
      Diet intervention to improve cardiovascular risk factors among iranian postmenopausal women.
      ], Canada [
      • Sénéchal M
      • Bouchard DR
      • Dionne IJ
      • Brochu M.
      The effects of lifestyle interventions in dynapenic-obese postmenopausal women.
      ], Australia [
      • Nowson CA
      • Wattanapenpaiboon N
      • Pachett A.
      Low-sodium Dietary Approaches to Stop Hypertension-type diet including lean red meat lowers blood pressure in postmenopausal women.
      ], Ireland [
      • Harrington M
      • Bennett T
      • Jakobsen J
      • Ovesen L
      • Brot C
      • Flynn A
      • et al.
      The effect of a high-protein, high-sodium diet on calcium and bone metabolism in postmenopausal women and its interaction with vitamin D receptor genotype.
      ], Italy [
      • Berrino F
      • Bellati C
      • Secreto G
      • Camerini E
      • Pala V.
      Reducing bioavailable sex hormones through a comprehensive change in diet: the diet and androgens (DIANA) randomized trial.
      ], Denmark [
      • Svendsen OL
      • Hassager C
      • Christiansen C.
      Effect of an energy-restrictive diet, with or without exercise, on lean tissue mass, resting metabolic rate, cardiovascular risk factors, and bone in overweight postmenopausal women.
      ], and one study was conducted in several centers (Miami, Atlanta, Birmingham, and Seattle) [
      • Dallas Hall W
      • Feng Z
      • George VA
      • Lewis CE
      • Oberman A
      • Huber M
      • et al.
      Low-fat diet: Effect on athropometrics, blood pressure, glucose, and insulin in older women.
      ]. Nine trials included an apparently healthy or general population of postmenopausal women [
      • Howard BV
      • Curb JD
      • Eaton CB
      • Kooperberg C
      • Ockene J
      • Kostis JB
      • et al.
      Low-fat dietary pattern and lipoprotein risk factors: The Women's Health Initiative Dietary Modification Trial.
      ,
      • Abedi P
      • Huang Soo Lee M
      • Yasin Z
      • Kandiah M
      Diet intervention to improve cardiovascular risk factors among iranian postmenopausal women.
      ,
      • Harrington M
      • Bennett T
      • Jakobsen J
      • Ovesen L
      • Brot C
      • Flynn A
      • et al.
      The effect of a high-protein, high-sodium diet on calcium and bone metabolism in postmenopausal women and its interaction with vitamin D receptor genotype.
      ,
      • Jeppesen J
      • Schaaf P
      • Jones C
      • Zhou MY
      • Ida Chen YD
      • Reaven GM
      Effects of low-fat, high-carbohydrate diets on risk factors for ischemic heart disease in postmenopausal women.
      ,
      • Kasim-Karakas SE
      • Almario RU
      • Mueller WM
      • Peerson J.
      Changes in plasma lipoproteins during low-fat, high-carbohydrate diets: effects of energy intake.
      ,
      • Berrino F
      • Bellati C
      • Secreto G
      • Camerini E
      • Pala V.
      Reducing bioavailable sex hormones through a comprehensive change in diet: the diet and androgens (DIANA) randomized trial.
      ,
      • Dallas Hall W
      • Feng Z
      • George VA
      • Lewis CE
      • Oberman A
      • Huber M
      • et al.
      Low-fat diet: Effect on athropometrics, blood pressure, glucose, and insulin in older women.
      ,
      • Ginsberg HN
      • Kris-Etherton P
      • Dennis B
      • Elmer PJ
      • Ershow A
      • Lefevre M
      • et al.
      Effects of reducing dietary saturated fatty acids on plasma lipids and lipoproteins in healthy subjects: The delta study, protocol 1.
      ,
      • Young LR
      • Kurzer MS
      • Thomas W
      • Redmon JB
      • Raatz SK.
      Low-fat diet with omega-3 fatty acids increases plasma insulin-like growth factor concentration in healthy postmenopausal women.
      ]. Twelve studies included women with a specific risk factor or history or disease only: six studies included obese or overweight participants only [
      • Mason C
      • Foster-Schubert KE
      • Imayama I
      • Kong A
      • Xiao L
      • Bain C
      • et al.
      Dietary weight loss and exercise effects on insulin resistance in postmenopausal women.
      ,
      • Barnard ND
      • Scialli AR
      • Turner-McGrievy G
      • Lanou AJ
      • Glass J.
      The effects of a low-fat, plant-based dietary intervention on body weight, metabolism, and insulin sensitivity.
      ,

      Segal-Isaacson CJ, Johnson S, Tomuta V. A randomized trial comparing low-fat and low-carbohydrate diets matched for energy and protein. Obesity …. 2004.

      ,
      • Mellberg C
      • Sandberg S
      • Ryberg M
      • Eriksson M
      • Brage S
      • Larsson C
      • et al.
      Long-term effects of a Palaeolithic-type diet in obese postmenopausal women: A 2-year randomized trial.
      ,
      • Sénéchal M
      • Bouchard DR
      • Dionne IJ
      • Brochu M.
      The effects of lifestyle interventions in dynapenic-obese postmenopausal women.
      ,
      • Svendsen OL
      • Hassager C
      • Christiansen C.
      Effect of an energy-restrictive diet, with or without exercise, on lean tissue mass, resting metabolic rate, cardiovascular risk factors, and bone in overweight postmenopausal women.
      ], one included only postmenopausal women with metabolic syndrome [

      Bajerska J, Chmurzynska A, Muzsik A. Weight loss and metabolic health effects from energy-restricted Mediterranean and Central-European diets in postmenopausal women: A randomized …: nature.com; 2018.

      ], one with hypertension [
      • Nowson CA
      • Wattanapenpaiboon N
      • Pachett A.
      Low-sodium Dietary Approaches to Stop Hypertension-type diet including lean red meat lowers blood pressure in postmenopausal women.
      ], one only moderate hypercholesterolemia [
      • Denke MA.
      Individual responsiveness to a cholesterol-lowering diet in postmenopausal women with moderate hypercholesterolemia.
      ], and three studies were conducted on women with a history of breast cancer [
      • Buzzard IM
      • Asp EH
      • Chlebowski RT
      • Boyar AP
      • Jeffery RW
      • Nixon DW
      • et al.
      Diet intervention methods to reduce fat intake: nutrient and food group composition of self-selected low-fat diets.
      ,
      • Murillo-Ortiz B
      • Martinez-Garza S
      • Landeros VC
      • Velazquez GC
      • Garcia DS.
      Effect of reduced dietary fat on estradiol, adiponectin, and IGF-1 levels in postmenopausal women with breast cancer.
      ,
      • Thomson CA
      • Stopeck AT
      • Bea JW
      • Cussler E
      • Nardi E
      • Frey G
      • et al.
      Changes in body weight and metabolic indexes in overweight breast cancer survivors enrolled in a randomized trial of low-fat vs. reduced carbohydrate diets.
      ]. Regarding dietary interventions, most of the trials intervened low/modified fat/fatty acids diets [
      • Howard BV
      • Curb JD
      • Eaton CB
      • Kooperberg C
      • Ockene J
      • Kostis JB
      • et al.
      Low-fat dietary pattern and lipoprotein risk factors: The Women's Health Initiative Dietary Modification Trial.
      ,
      • Barnard ND
      • Scialli AR
      • Turner-McGrievy G
      • Lanou AJ
      • Glass J.
      The effects of a low-fat, plant-based dietary intervention on body weight, metabolism, and insulin sensitivity.
      ,
      • Buzzard IM
      • Asp EH
      • Chlebowski RT
      • Boyar AP
      • Jeffery RW
      • Nixon DW
      • et al.
      Diet intervention methods to reduce fat intake: nutrient and food group composition of self-selected low-fat diets.
      ,
      • Denke MA.
      Individual responsiveness to a cholesterol-lowering diet in postmenopausal women with moderate hypercholesterolemia.
      ,
      • Jeppesen J
      • Schaaf P
      • Jones C
      • Zhou MY
      • Ida Chen YD
      • Reaven GM
      Effects of low-fat, high-carbohydrate diets on risk factors for ischemic heart disease in postmenopausal women.
      ,
      • Kasim-Karakas SE
      • Almario RU
      • Mueller WM
      • Peerson J.
      Changes in plasma lipoproteins during low-fat, high-carbohydrate diets: effects of energy intake.
      ,
      • Murillo-Ortiz B
      • Martinez-Garza S
      • Landeros VC
      • Velazquez GC
      • Garcia DS.
      Effect of reduced dietary fat on estradiol, adiponectin, and IGF-1 levels in postmenopausal women with breast cancer.
      ,
      • Thomson CA
      • Stopeck AT
      • Bea JW
      • Cussler E
      • Nardi E
      • Frey G
      • et al.
      Changes in body weight and metabolic indexes in overweight breast cancer survivors enrolled in a randomized trial of low-fat vs. reduced carbohydrate diets.
      ,
      • Dallas Hall W
      • Feng Z
      • George VA
      • Lewis CE
      • Oberman A
      • Huber M
      • et al.
      Low-fat diet: Effect on athropometrics, blood pressure, glucose, and insulin in older women.
      ,
      • Ginsberg HN
      • Kris-Etherton P
      • Dennis B
      • Elmer PJ
      • Ershow A
      • Lefevre M
      • et al.
      Effects of reducing dietary saturated fatty acids on plasma lipids and lipoproteins in healthy subjects: The delta study, protocol 1.
      ,
      • Young LR
      • Kurzer MS
      • Thomas W
      • Redmon JB
      • Raatz SK.
      Low-fat diet with omega-3 fatty acids increases plasma insulin-like growth factor concentration in healthy postmenopausal women.
      ] and other interventions included Mediterranean diet [

      Bajerska J, Chmurzynska A, Muzsik A. Weight loss and metabolic health effects from energy-restricted Mediterranean and Central-European diets in postmenopausal women: A randomized …: nature.com; 2018.

      ], Paleolithic diet [
      • Mellberg C
      • Sandberg S
      • Ryberg M
      • Eriksson M
      • Brage S
      • Larsson C
      • et al.
      Long-term effects of a Palaeolithic-type diet in obese postmenopausal women: A 2-year randomized trial.
      ], healthy diet [
      • Abedi P
      • Huang Soo Lee M
      • Yasin Z
      • Kandiah M
      Diet intervention to improve cardiovascular risk factors among iranian postmenopausal women.
      ], diet based on American Heart Association recommendations [
      • Sénéchal M
      • Bouchard DR
      • Dionne IJ
      • Brochu M.
      The effects of lifestyle interventions in dynapenic-obese postmenopausal women.
      ], low-sodium DASH-type diet [
      • Nowson CA
      • Wattanapenpaiboon N
      • Pachett A.
      Low-sodium Dietary Approaches to Stop Hypertension-type diet including lean red meat lowers blood pressure in postmenopausal women.
      ], very low-carbohydrates diet [

      Segal-Isaacson CJ, Johnson S, Tomuta V. A randomized trial comparing low-fat and low-carbohydrate diets matched for energy and protein. Obesity …. 2004.

      ], high-sodium, high- protein diet [
      • Harrington M
      • Bennett T
      • Jakobsen J
      • Ovesen L
      • Brot C
      • Flynn A
      • et al.
      The effect of a high-protein, high-sodium diet on calcium and bone metabolism in postmenopausal women and its interaction with vitamin D receptor genotype.
      ], plant-based diet [
      • Berrino F
      • Bellati C
      • Secreto G
      • Camerini E
      • Pala V.
      Reducing bioavailable sex hormones through a comprehensive change in diet: the diet and androgens (DIANA) randomized trial.
      ], weight-loss diet [
      • Mason C
      • Foster-Schubert KE
      • Imayama I
      • Kong A
      • Xiao L
      • Bain C
      • et al.
      Dietary weight loss and exercise effects on insulin resistance in postmenopausal women.
      ], and energy-restricted diet [
      • Svendsen OL
      • Hassager C
      • Christiansen C.
      Effect of an energy-restrictive diet, with or without exercise, on lean tissue mass, resting metabolic rate, cardiovascular risk factors, and bone in overweight postmenopausal women.
      ]. Four trials provided isocaloric diets [
      • Jeppesen J
      • Schaaf P
      • Jones C
      • Zhou MY
      • Ida Chen YD
      • Reaven GM
      Effects of low-fat, high-carbohydrate diets on risk factors for ischemic heart disease in postmenopausal women.
      ,

      Segal-Isaacson CJ, Johnson S, Tomuta V. A randomized trial comparing low-fat and low-carbohydrate diets matched for energy and protein. Obesity …. 2004.

      ,
      • Ginsberg HN
      • Kris-Etherton P
      • Dennis B
      • Elmer PJ
      • Ershow A
      • Lefevre M
      • et al.
      Effects of reducing dietary saturated fatty acids on plasma lipids and lipoproteins in healthy subjects: The delta study, protocol 1.
      ,
      • Young LR
      • Kurzer MS
      • Thomas W
      • Redmon JB
      • Raatz SK.
      Low-fat diet with omega-3 fatty acids increases plasma insulin-like growth factor concentration in healthy postmenopausal women.
      ], and the diets of five trials were ad libitum or self-selected, or were not isocaloric [
      • Barnard ND
      • Scialli AR
      • Turner-McGrievy G
      • Lanou AJ
      • Glass J.
      The effects of a low-fat, plant-based dietary intervention on body weight, metabolism, and insulin sensitivity.
      ,
      • Buzzard IM
      • Asp EH
      • Chlebowski RT
      • Boyar AP
      • Jeffery RW
      • Nixon DW
      • et al.
      Diet intervention methods to reduce fat intake: nutrient and food group composition of self-selected low-fat diets.
      ,
      • Berrino F
      • Bellati C
      • Secreto G
      • Camerini E
      • Pala V.
      Reducing bioavailable sex hormones through a comprehensive change in diet: the diet and androgens (DIANA) randomized trial.
      ,
      • Dallas Hall W
      • Feng Z
      • George VA
      • Lewis CE
      • Oberman A
      • Huber M
      • et al.
      Low-fat diet: Effect on athropometrics, blood pressure, glucose, and insulin in older women.
      ,
      • Mellberg C
      • Sandberg S
      • Ryberg M
      • Eriksson M
      • Brage S
      • Larsson C
      • et al.
      Long-term effects of a Palaeolithic-type diet in obese postmenopausal women: A 2-year randomized trial.
      ]. The rest of included studies did not provide information on whether diets were isocaloric. In six trials, prepared meals or raw food ingredients were provided to the participants [

      Bajerska J, Chmurzynska A, Muzsik A. Weight loss and metabolic health effects from energy-restricted Mediterranean and Central-European diets in postmenopausal women: A randomized …: nature.com; 2018.

      ,
      • Murillo-Ortiz B
      • Martinez-Garza S
      • Landeros VC
      • Velazquez GC
      • Garcia DS.
      Effect of reduced dietary fat on estradiol, adiponectin, and IGF-1 levels in postmenopausal women with breast cancer.
      ,
      • Nowson CA
      • Wattanapenpaiboon N
      • Pachett A.
      Low-sodium Dietary Approaches to Stop Hypertension-type diet including lean red meat lowers blood pressure in postmenopausal women.
      ,

      Segal-Isaacson CJ, Johnson S, Tomuta V. A randomized trial comparing low-fat and low-carbohydrate diets matched for energy and protein. Obesity …. 2004.

      ,
      • Ginsberg HN
      • Kris-Etherton P
      • Dennis B
      • Elmer PJ
      • Ershow A
      • Lefevre M
      • et al.
      Effects of reducing dietary saturated fatty acids on plasma lipids and lipoproteins in healthy subjects: The delta study, protocol 1.
      ,
      • Young LR
      • Kurzer MS
      • Thomas W
      • Redmon JB
      • Raatz SK.
      Low-fat diet with omega-3 fatty acids increases plasma insulin-like growth factor concentration in healthy postmenopausal women.
      ] and in one study only the pre-prepared meals were obtained for the control group [
      • Kasim-Karakas SE
      • Almario RU
      • Mueller WM
      • Peerson J.
      Changes in plasma lipoproteins during low-fat, high-carbohydrate diets: effects of energy intake.
      ]. The remaining trials included nutrition counseling, individual goals, and meals/cooking classes as the intervention methods. The intervention duration ranged between 3 weeks to 12 months for most studies, one study lasted for 2 years and one for 6 years [
      • Howard BV
      • Curb JD
      • Eaton CB
      • Kooperberg C
      • Ockene J
      • Kostis JB
      • et al.
      Low-fat dietary pattern and lipoprotein risk factors: The Women's Health Initiative Dietary Modification Trial.
      ,
      • Mellberg C
      • Sandberg S
      • Ryberg M
      • Eriksson M
      • Brage S
      • Larsson C
      • et al.
      Long-term effects of a Palaeolithic-type diet in obese postmenopausal women: A 2-year randomized trial.
      ]. Fourteen trials were designed as parallel [
      • Howard BV
      • Curb JD
      • Eaton CB
      • Kooperberg C
      • Ockene J
      • Kostis JB
      • et al.
      Low-fat dietary pattern and lipoprotein risk factors: The Women's Health Initiative Dietary Modification Trial.
      ,
      • Abedi P
      • Huang Soo Lee M
      • Yasin Z
      • Kandiah M
      Diet intervention to improve cardiovascular risk factors among iranian postmenopausal women.
      ,
      • Mason C
      • Foster-Schubert KE
      • Imayama I
      • Kong A
      • Xiao L
      • Bain C
      • et al.
      Dietary weight loss and exercise effects on insulin resistance in postmenopausal women.
      ,

      Bajerska J, Chmurzynska A, Muzsik A. Weight loss and metabolic health effects from energy-restricted Mediterranean and Central-European diets in postmenopausal women: A randomized …: nature.com; 2018.

      ,
      • Barnard ND
      • Scialli AR
      • Turner-McGrievy G
      • Lanou AJ
      • Glass J.
      The effects of a low-fat, plant-based dietary intervention on body weight, metabolism, and insulin sensitivity.
      ,
      • Buzzard IM
      • Asp EH
      • Chlebowski RT
      • Boyar AP
      • Jeffery RW
      • Nixon DW
      • et al.
      Diet intervention methods to reduce fat intake: nutrient and food group composition of self-selected low-fat diets.
      ,
      • Murillo-Ortiz B
      • Martinez-Garza S
      • Landeros VC
      • Velazquez GC
      • Garcia DS.
      Effect of reduced dietary fat on estradiol, adiponectin, and IGF-1 levels in postmenopausal women with breast cancer.
      ,
      • Nowson CA
      • Wattanapenpaiboon N
      • Pachett A.
      Low-sodium Dietary Approaches to Stop Hypertension-type diet including lean red meat lowers blood pressure in postmenopausal women.
      ,
      • Thomson CA
      • Stopeck AT
      • Bea JW
      • Cussler E
      • Nardi E
      • Frey G
      • et al.
      Changes in body weight and metabolic indexes in overweight breast cancer survivors enrolled in a randomized trial of low-fat vs. reduced carbohydrate diets.
      ,
      • Berrino F
      • Bellati C
      • Secreto G
      • Camerini E
      • Pala V.
      Reducing bioavailable sex hormones through a comprehensive change in diet: the diet and androgens (DIANA) randomized trial.
      ,
      • Dallas Hall W
      • Feng Z
      • George VA
      • Lewis CE
      • Oberman A
      • Huber M
      • et al.
      Low-fat diet: Effect on athropometrics, blood pressure, glucose, and insulin in older women.
      ,
      • Mellberg C
      • Sandberg S
      • Ryberg M
      • Eriksson M
      • Brage S
      • Larsson C
      • et al.
      Long-term effects of a Palaeolithic-type diet in obese postmenopausal women: A 2-year randomized trial.
      ,
      • Sénéchal M
      • Bouchard DR
      • Dionne IJ
      • Brochu M.
      The effects of lifestyle interventions in dynapenic-obese postmenopausal women.
      ,
      • Svendsen OL
      • Hassager C
      • Christiansen C.
      Effect of an energy-restrictive diet, with or without exercise, on lean tissue mass, resting metabolic rate, cardiovascular risk factors, and bone in overweight postmenopausal women.
      ] and seven were designed as cross-over [
      • Denke MA.
      Individual responsiveness to a cholesterol-lowering diet in postmenopausal women with moderate hypercholesterolemia.
      ,
      • Harrington M
      • Bennett T
      • Jakobsen J
      • Ovesen L
      • Brot C
      • Flynn A
      • et al.
      The effect of a high-protein, high-sodium diet on calcium and bone metabolism in postmenopausal women and its interaction with vitamin D receptor genotype.
      ,
      • Jeppesen J
      • Schaaf P
      • Jones C
      • Zhou MY
      • Ida Chen YD
      • Reaven GM
      Effects of low-fat, high-carbohydrate diets on risk factors for ischemic heart disease in postmenopausal women.
      ,
      • Kasim-Karakas SE
      • Almario RU
      • Mueller WM
      • Peerson J.
      Changes in plasma lipoproteins during low-fat, high-carbohydrate diets: effects of energy intake.
      ,

      Segal-Isaacson CJ, Johnson S, Tomuta V. A randomized trial comparing low-fat and low-carbohydrate diets matched for energy and protein. Obesity …. 2004.

      ,
      • Ginsberg HN
      • Kris-Etherton P
      • Dennis B
      • Elmer PJ
      • Ershow A
      • Lefevre M
      • et al.
      Effects of reducing dietary saturated fatty acids on plasma lipids and lipoproteins in healthy subjects: The delta study, protocol 1.
      ,
      • Young LR
      • Kurzer MS
      • Thomas W
      • Redmon JB
      • Raatz SK.
      Low-fat diet with omega-3 fatty acids increases plasma insulin-like growth factor concentration in healthy postmenopausal women.
      ]. Characteristics of the included studies are presented in Table 1.
      Table 1Characteristics of the included studies.
      SourceCountry/ Study name1Design/ RandomizationNo. of Participants/ InterventionAge2 (years)Health statusInterventionControlDurationDietary intake assessmentResults
      General/healthy population of postmenopausal women
      Young3, 2013
      • Nelson HD.
      United statesC/ R17/ 1757±6Healthy1- Low-fat diet: 20 E% fats, 65 E% CHO, 15 E% Pr 2- Low-fat, high n-3 diet:23 E fats, 62 E% CHO, 15 E% PrHigh-fat diet: 40 E% fat, 45 E% CHO, 15 E% Pr8 wDaily compliance recordsInsulin, FBS, HOMA
      McColley3, 2011
      • Rosano GM
      • Vitale C
      • Marazzi G
      • Volterrani M.
      Menopause and cardiovascular disease: the evidence.
      United statesC/ R16/ 1656.3±1.5Healthy1- Low-fat diet: 20 E% fats, 65 E% CHO, 15 E% Pr. 2- Low-fat, high n-3 diet: 23 E fats, 62 E% CHO, 15 E% PrHigh-fat diet: 40 E% fat, 45 E% CHO, 15 E% Pr8 wDaily compliance recordsTG↓C
      Jeppesen, 1997
      • Crandall CJ
      • Barrett-Connor E.
      Endogenous sex steroid levels and cardiovascular disease in relation to the menopause: a systematic review.
      United statesC/ R10/566±5Healthy, non-diabeticLow-fat, high- CHO diet: 25 E% fats, 60 E% CHO, 5 E% PrHigh-fat, low-CHO diet: 45 E% fats, 40 E% CHO, 15 E% Pr3 wNMTG↑*, TC, VLDL↑*, LDL, HDL↓*,TC:HDL↑ *
      Kasim-Karakas£, 2000
      • Zhao D
      • Guallar E
      • Ouyang P
      • Subramanya V
      • Vaidya D
      • Ndumele CE
      • et al.
      Endogenous Sex Hormones and Incident Cardiovascular Disease in Post-Menopausal Women.
      United statesC/ NR54/ 5461±11HealthyLow-fat diet: 15E% fats1- 35%-fat diet 2- 25%-fat diet8 m7-day food recordsInsulin, FBS↓*, HbA1C
      Shikany4, 2011
      • Carr MC.
      The emergence of the metabolic syndrome with menopause.
      United states/ WHI DMP/ R2,263/ 892I:61.5±6.9 C:61.6±6.8General population, without T1DM and cancerLow-fat diet: reducing total fat intake to 20% of energy, increasing vegetable and fruit intakes to ≥5 servings and grainDietary Guidelines for Americans and other health-related materials6 yFFQInsulin, FBS, HOMA, QUICKI
      Howard4, 2010
      • Karlamangla AS
      • Burnett-Bowie SM
      • Crandall CJ.
      Bone Health During the Menopause Transition and Beyond.
      United states/ WHI DMP/ R2,730/ 1,068I:61.6±6.9 C:61.8±6.9General population, without T1DM and cancerLow-fat diet: reducing total fat intake to 20% of energy, increasing vegetable and fruit intakes to ≥5 servings and grainDietary Guidelines for Americans and other Health-related materials6 yFFQTC, LDL, HDL, TG, non-HDL, TC:HDL, Lp[a]
      Tinker4, 2008
      • Assaf AR
      • Bushmakin AG
      • Joyce N
      • Louie MJ
      • Flores M
      • Moffatt M.
      The Relative Burden of Menopausal and Postmenopausal Symptoms versus Other Major Conditions: A Retrospective Analysis of the Medical Expenditure Panel Survey Data.
      United states/ WHI DMP/ R45,887/18,376I:62.2±6.9 C:62.2±6.9General population, without T1DM and cancerLow-fat diet: reducing total fat intake to 20% of energy, increasing vegetable and fruit intakes to ≥5 servings and grainDietary Guidelines for Americans and other Health-related materials6 yFFQSBP, DBP
      Bhargava5, 2006
      • Slopien R
      • Wender-Ozegowska E
      • Rogowicz-Frontczak A
      • Meczekalski B
      • Zozulinska-Ziolkiewicz D
      • Jaremek JD
      • et al.
      Menopause and diabetes: EMAS clinical guide.
      Multicenter#/ WHTFSMPP/ R994/ 61550-79General populationlow-fat diet: Reducing energy intakes from fat to 20% and increasing the consumption of fruits, vegetables, and grain productsGeneral dietary guideline recommendations12 mFFQLDL↓IC*, HDL↓IC*
      Dallas Hall5, 2003
      • Ganz PA.
      Breast cancer, menopause, and long-term survivorship: critical issues for the 21st century.
      Multicenter#/ WHTFSMPP/ RGlycemic: 1,067/660 BP: 1,749/ 1,10150-79General populationlow-fat diet: Reducing energy intakes from fat to 20% and increasing the consumption of fruits, vegetables, and grain productsGeneral dietary guideline recommendations6 mFFQInsulin, FBS, SBP↓*, DBP
      Ginsberg, 1998
      • Vellanki K
      • Hou S.
      Menopause in CKD.
      Multicenter##/ DELTAC/ R18/ 1857.5Healthy1- NCEP: 30 E% fats (9 E% SFA, 14 E% MUFA, and 7 E% PUFA), 55 E% CHO, 15 E% Pr. 2- Low-Sat diet: 26 E% fats (5 E% SFA, 14 E% MUFA, and 7 E% PUFA), 59 E% CHO, 15 E % PrAverage American diet: 37 E% fats (16 E% SFA, 14 E% MUFA, and 7 E% PUFA), 48 E% CHO, 15 E% Pr8 wNMTC↓*, LDL↓*, HDL↓*, TG, Apo A-1↓*^, Apo B, Lp(a) ↑*^, TC:HDL
      Harrington, 2004
      • El Khoudary SR
      • Aggarwal B
      • Beckie TM
      • Hodis HN
      • Johnson AE
      • Langer RD
      • et al.
      Menopause Transition and Cardiovascular Disease Risk: Implications for Timing of Early Prevention: A Scientific Statement From the.
      IrelandC/ R26/2657.1±5.1HealthyHigh-sodium, high- protein diet: 180 mmol/d day of Na and 90 g/day of PrLow- sodium, usual-protein intake4 w4-day food recordsSBP, DBP
      Abedi, 2012
      • Yu E
      • Malik VS
      • Hu FB.
      Cardiovascular Disease Prevention by Diet Modification: JACC Health Promotion Series.
      IranP/ R64/ 35I:51.4 ±4.9 C:51.6±5.7HealthyHealthy diet: fruits and vegetables ≥5 servings, whole grain foods, high fiber foods, fish (two times per week), <10 E% SFA, cholesterol <300 mg/day, salt <5 g/dayHabitual intakes6 m24-hour recallTC↓IC, TG↓I, LDL, HDL, FBS↓I, SBP, DBP
      Muti6, 2003
      • Noll P
      • Campos CAS
      • Leone C
      • Zangirolami-Raimundo J
      • Noll M
      • Baracat EC
      • et al.
      Dietary intake and menopausal symptoms in postmenopausal women: a systematic review.
      Italy/ DIANAP/ R99/ 5050-65HealthyPlant based diet: Mediterranean vegetarian and macrobiotic recipesA leaflet based on Europe against Cancer program: were advised to increase the fruit and vegetables consumption.18 w24-h diariesTC↓*
      Berrino6, 2001
      • Prentice RL
      • Pettinger M
      • Neuhouser ML
      • Raftery D
      • Zheng C
      • Gowda GAN
      • et al.
      Biomarker-Calibrated Macronutrient Intake and Chronic Disease Risk among Postmenopausal Women.
      Italy/ DIANAP/ R99/ 5050-65HealthyPlant based diet: Mediterranean vegetarian and macrobiotic recipes.A leaflet based on Europe against Cancer program: were advised to increase the fruit and vegetables consumption.18 w24-h diariesInsulin, FBS
      Postmenopausal women with cardiovascular risk factors
      Barnard, 2005
      • Moradi M
      • Daneshzad E
      • Azadbakht L.
      The effects of isolated soy protein, isolated soy isoflavones and soy protein containing isoflavones on serum lipids in postmenopausal women: A systematic review and meta-analysis.
      United statesP/ R59/ 29I:57.4 C:55.6OverweightLow-fat, plant-based diet: 10 E% fats, 75 E% CHO, 15 E% PrNCEP: 30 E% fat (7 E% SFA), 55 E% CHO, 15 E% Pr, Cholesterol <200 mg/day14 w3-day food recordInsulin↓I, FBS↓I, Insulin sensitivity↑I
      Denke, 1994
      • Liu C
      • Kuang X
      • Li K
      • Guo X
      • Deng Q
      • Li D.
      Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials.
      United statesC/ NR39/ 3961±6Moderate hypercholesterolemiaFat-modified step 1 diet: Based on NCEP and AHA recommendations (30 E% fats, 10 E% saturated fats, <300 mg/d dietary cholesterol )High-Sat diet: 40 E% fats, 16 E% SFA, 450 mg/d dietary cholesterol3 m7-day food recordsTC↓I*, LDL↓I*, VLDL, HDL, TG
      C J Segal-Isaacson 2004

      Patade A, Devareddy L, Lucas EA, Korlagunta K, Daggy BP, Arjmandi BH. Flaxseed reduces total and LDL cholesterol concentrations in Native American postmenopausal women. Journal of women's health (2002). 2008;17(3):355-66.

      United statesC/ R4/252.3±3.8Overweight/obeseVery low-CHO diet: 5 E% to 10 E% CHOLow-fat diet: Same energy and protein content6 wFFQTC↓IC, TG↓I, LDL↓IC, HDL↓IC, Insulin, FBS↓IC
      Svendsen, 1993
      • Glisic M
      • Kastrati N
      • Musa J
      • Milic J
      • Asllanaj E
      • Portilla Fernandez E
      • et al.
      Phytoestrogen supplementation and body composition in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials.
      DenmarkP/ R72/5153.8±2.5OverweightEnergy-restricted Diet: Up to 4.2 MJ/day.Habitual intakes12 w7-day food diaryTG↓*, TC↓*, HDL, VLDL↓*, LDL↓*, HDL:LDL↑*, SBP↓*, DBP
      Mason, 2011
      • Howard BV
      • Curb JD
      • Eaton CB
      • Kooperberg C
      • Ockene J
      • Kostis JB
      • et al.
      Low-fat dietary pattern and lipoprotein risk factors: The Women's Health Initiative Dietary Modification Trial.
      United states/ NEWP/ R185/ 105I:58.1±5.9 C:57.4±4.4Overweight/obese1200–2000 kcal/day, <30 E% fats, and 10% weight lossHabitual intakes12 mFFQInsulin↓*, FBS↓*, HOMA↓*
      Se´ne´chal, 2012
      • Tinker LF
      • Bonds DE
      • Margolis KL
      • Manson JE
      • Howard BV
      • Larson J
      • et al.
      Low-fat dietary pattern and risk of treated diabetes mellitus in postmenopausal women: The women's health initiative randomized controlled dietary modification trial.
      CanadaP/ R19/ 962.6±4.1ObeseAHA recommendations: 30 E% fats, 55 E% CHO, 15 E% PrHabitual intakes12 wFood diaryTC↓I, TG↓I, HDL↓I*, LDL↓I, TC:HDL, Insulin, FBS, HOMA, QUICKI, SBP↓I, DBP↓I
      Bajerska, 2018
      • Abedi P
      • Huang Soo Lee M
      • Yasin Z
      • Kandiah M
      Diet intervention to improve cardiovascular risk factors among iranian postmenopausal women.
      PolandP/ R144/ 7260.5Metabolic SyndromeMediterranean diet: 37 E% fats (20 E% MUFA, 9 E% PUFA, 8 E% SFA), 45 E% CHO, 18 E% PrCentral European diet: Based on NCEP and AHA recommendations (27 E% fats [10 E% MUFA, 9 E% PUFA, 8 E% SFA], 55 E% CHO, 18 E% Pr. Emphasis on dietary fiber)16 w3-day food diaryTC↓IC, LDL↓I, HDL↓C, TG↓IC, Insulin↓IC, FBS↓IC, HOMA↓IC, SBP↓IC, DBP↓IC
      Otten7, 2016
      • Mason C
      • Foster-Schubert KE
      • Imayama I
      • Kong A
      • Xiao L
      • Bain C
      • et al.
      Dietary weight loss and exercise effects on insulin resistance in postmenopausal women.
      SwedenP/ R41/ 25I:61±6 C:62±6ObesePaleolithic diet: 40 E% fats, 30 E% CHO, 30 E% Pr. Recommended to intake higher MUFA and PUFANordic Nutrition Recommendations (4th edition): 25–30 E% fats, 55–60 E% CHO, 15 E% Pr. Emphasis on low-fat dairy products and high-fiber products24 m4-day food recordsHOMA
      Mellberg7, 2014
      • Wu L
      • Ma D
      • Walton-Moss B
      • He Z.
      Effects of low-fat diet on serum lipids in premenopausal and postmenopausal women: a meta-analysis of randomized controlled trials.
      SwedenP/ R49/ 27I:59.5±5.5 C:60.3±5.9ObesePaleolithic diet: 40 E% fats, 30 E% CHO, 30 E% Pr. Recommended to intake higher MUFA and PUFANordic Nutrition Recommendations (4th edition): 25–30 E% fats, 55–60 E% CHO, 15 E% Pr. Emphasis on low-fat dairy products and high-fiber products24 m4-day food recordsTC, HDL, LDL, TG↓I*, Insulin, FBS, SBP, DBP,
      Nowson, 2009
      • Liberati A
      • Altman DG
      • Tetzlaff J
      • Mulrow C
      • Gøtzsche PC
      • Ioannidis JP
      • et al.
      The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.
      AustraliaP/ R95/46I:60±0.7 C:58.4±0.7HypertensiveLow-sodium DASH-type diet: with a low dietary acid load containing 6 servings of 100g lean red meat/week. Rich in fruit and vegetables and had a higher potassium and magnesium content.Higher acid load healthy diet: based on general dietary guidelines to reduce fat intake and increase intake of breads and cereals14 w3-day food recordSBP↓IC, DBP↓IC,
      Postmenopausal women with breast cancer
      Buzzard, 1990
      • Moher D
      • Liberati A
      • Tetzlaff J
      • Altman DG
      • Group P.
      Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
      United statesP/ R28/ 17I:60±2 C:61±3Breast cancerLow-fat diet: Reducing total fat intake, using combination of education, goal setting, evaluation, feedback, and participant self-monitoring.No counseling regarding fat intake3 m4-day food recordsTC↓I
      Thomson 2010
      • Sterne JAC
      • Savović J
      • Page MJ
      • Elbers RG
      • Blencowe NS
      • Boutron I
      • et al.
      RoB 2: a revised tool for assessing risk of bias in randomised trials.
      United statesP/ R38/2057.8±9.3Breast cancer survivorsLow-fat diet: 25 E% fats, 55–60 E% CHO, 15–20 E% PrLow-CHO diet: Modified Atkins diet (35–40 E% fats with greater MUFA, 35 E% CHO, 25–30 E% Pr)24 wFFQTC↓I, LDL↓I, HDL↑I, TC:HDL, TG↓C, FBS, HbA1c↓C, Insulin↓C, HOMA↓IC, QUICKI↓I, SBP↓I, DBP,
      Murillo-Ortiz, 2017
      • Sterne JA
      • Hernán MA
      • Reeves BC
      • Savović J
      • Berkman ND
      • Viswanathan M
      • et al.
      ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions.
      MexicoP/ R100/ 50I:50.5±7.9 C:52.3±6.1Breast cancerLow-fat diet: 12 E% fats, 68 E% CHO, 20 E% PrAmerican Dietetic Association: 30 E% fats, 50 E% CHO, 20 E% Pr6 mNMFBS↓I
      1If available, the name of the studies are reported. 2 Age is presented as either mean ± SD or min-max as years. R: Randomized; NR: Non-Randomized; P: Parallel; C: Cross-over; m: Months; w: Weeks; NM: Not mentioned; y: Years; E%: Percent of energy intake; CHO: Carbohydrates; Pr: Proteins; PUFA: Polyunsaturated fatty acids; MUFA: Monounsaturated fatty acids; BP: Blood pressure; FFQ: Food frequency questionnaire; AHA: American Heart Association; NCEP: National Cholesterol Education Program; DASH: dietary approaches to stop hypertension; TG: Triglyceride; TC: Total cholesterol; LDL: Low-density lipoprotein cholesterol; VLDL: Very low-density lipoprotein cholesterol; HDL: High-density lipoprotein cholesterol; Apo: Apo lipoprotein; TC:HDL: TC to HDL ratio; Lp(a): Lipoprotein(a); FBS: Fasting blood sugar; HOMA: Homeostatic Model Assessment for Insulin Resistance; QUICKI: Quantitative insulin sensitivity check index; HbA1c: Hemoglobin A1c; SBP: Systolic blood pressure; DBP: Diastolic blood pressure;
      I Significant changes within intervention group. C Significant changes within control group. *Significant changes in the intervention group compared to the control group.
      ^ Only one of the interventions (low-Sat diet) compared to the control.
      3 Both articles were conducted on a same project. 4 These papers were published from findings of the Women's Health Initiative Randomized Controlled Dietary Modification Trial (WHI DM). 5 These papers were derived from Women's Health Trial: Feasibility Study in Minority Populations (WHT:FSMP). 6 These papers were derived from Diet and Androgens Study (DIANA). 7 These papers are derived from the same project.
      £ Although this study reported some other outcomes of interest, we decided to only use glycemic indices results. In this study, dietary intervention accrued in two phases: 15% fat diet (as the intervention) and low-fat diets in which fat intake was reduced in a stepwise manner from 35% to 15% (as the control). The last diet in the control duration (15%) was similar to the intervention diet, so we decided to extract only findings that compare the effects of intervention diet to 35% and 25% fat diets as the control periods.
      # Three clinical centers (Miami, Atlanta, Birmingham) and the Fred Hutchinson Cancer Research Center in Seattle. ## Columbia University, Pennington Biomedical Research Center, Pennsylvania State University, and University of Minnesota.

      3.3 Quality and Risk of Bias

      The details of risk of bias of 19 trials based on RoB 2 domains are summarized in Table 2. Among the included studies, 2 trials did not provide any information on randomization, thus we assumed them as non-randomized trials. The quality of these studies are presented in Table 3 using ROBINS-I tool. For randomized controlled trials, overall risk identified “High risk” for two studies [
      • Abedi P
      • Huang Soo Lee M
      • Yasin Z
      • Kandiah M
      Diet intervention to improve cardiovascular risk factors among iranian postmenopausal women.
      ,
      • Svendsen OL
      • Hassager C
      • Christiansen C.
      Effect of an energy-restrictive diet, with or without exercise, on lean tissue mass, resting metabolic rate, cardiovascular risk factors, and bone in overweight postmenopausal women.
      ] and the rest of studies were identified as “Some concerns”. Concerning the non-randomized trials, one scored as “Critical” [
      • Denke MA.
      Individual responsiveness to a cholesterol-lowering diet in postmenopausal women with moderate hypercholesterolemia.
      ] and the other one as “Serious” [
      • Kasim-Karakas SE
      • Almario RU
      • Mueller WM
      • Peerson J.
      Changes in plasma lipoproteins during low-fat, high-carbohydrate diets: effects of energy intake.
      ].
      Table 2Risk of bias in randomized trials (RoB 2 tool).
      First author, yearRandomization processdeviations from intended interventionsmissing outcome datameasurement of the outcomeselection of the reported resultOverall assessment
      McColley et al., 2011
      • Nelson HD.
      Some concernsSome concernsLow risk of biasSome concernsLow risk of biasSome concerns
      Jeppesen et al., 1997
      • Rosano GM
      • Vitale C
      • Marazzi G
      • Volterrani M.
      Menopause and cardiovascular disease: the evidence.
      Some concernsSome concernsLow risk of biasSome concernsLow risk of biasSome concerns
      Howard et al., 2006
      • Crandall CJ
      • Barrett-Connor E.
      Endogenous sex steroid levels and cardiovascular disease in relation to the menopause: a systematic review.
      Some concernsSome concernsLow risk of biasLow risk of biasLow risk of biasSome concerns
      Dallas Hall et al., 2003
      • Zhao D
      • Guallar E
      • Ouyang P
      • Subramanya V
      • Vaidya D
      • Ndumele CE
      • et al.
      Endogenous Sex Hormones and Incident Cardiovascular Disease in Post-Menopausal Women.
      Some concernsSome concernsSome concernsLow risk of biasLow risk of biasSome concerns
      Ginsberg et al., 1998
      • Carr MC.
      The emergence of the metabolic syndrome with menopause.
      Some concernsLow risk of biasSome concernsSome concernsLow risk of biasSome concerns
      Harrington et al., 2004
      • Karlamangla AS
      • Burnett-Bowie SM
      • Crandall CJ.
      Bone Health During the Menopause Transition and Beyond.
      Some concernsSome concernsLow risk of biasSome concernsLow risk of biasSome concerns
      Abedi et al., 2010
      • Assaf AR
      • Bushmakin AG
      • Joyce N
      • Louie MJ
      • Flores M
      • Moffatt M.
      The Relative Burden of Menopausal and Postmenopausal Symptoms versus Other Major Conditions: A Retrospective Analysis of the Medical Expenditure Panel Survey Data.
      Some concernsSome concernsHigh risk of biasSome concernsLow risk of biasHigh risk of bias
      Berrino et al., 2001
      • Slopien R
      • Wender-Ozegowska E
      • Rogowicz-Frontczak A
      • Meczekalski B
      • Zozulinska-Ziolkiewicz D
      • Jaremek JD
      • et al.
      Menopause and diabetes: EMAS clinical guide.
      Some concernsSome concernsLow risk of biasLow risk of biasLow risk of biasSome concerns
      Barnard et al., 2005
      • Ganz PA.
      Breast cancer, menopause, and long-term survivorship: critical issues for the 21st century.
      Some concernsSome concernsLow risk of biasSome concernsLow risk of biasSome concerns
      C J Segal-Isaacson 2004
      • Vellanki K
      • Hou S.
      Menopause in CKD.
      Some concernsSome concernsSome concernsSome concernsLow risk of biasSome concerns
      Svendsen et al., 1993
      • El Khoudary SR
      • Aggarwal B
      • Beckie TM
      • Hodis HN
      • Johnson AE
      • Langer RD
      • et al.
      Menopause Transition and Cardiovascular Disease Risk: Implications for Timing of Early Prevention: A Scientific Statement From the.
      High risk of biasSome concernsLow risk of biasLow risk of biasLow risk of biasHigh risk of bias
      Mason et al, 2011
      • Yu E
      • Malik VS
      • Hu FB.
      Cardiovascular Disease Prevention by Diet Modification: JACC Health Promotion Series.
      Some concernsSome concernsLow risk of biasLow risk of biasLow risk of biasSome concerns
      Se´ne´chal et al. 2011[13]Some concernsSome concernsLow risk of biasSome concernsLow risk of biasSome concerns
      Bajerska et al., 2018
      • Prentice RL
      • Pettinger M
      • Neuhouser ML
      • Raftery D
      • Zheng C
      • Gowda GAN
      • et al.
      Biomarker-Calibrated Macronutrient Intake and Chronic Disease Risk among Postmenopausal Women.
      Low risk of biasSome concernsLow risk of biasLow risk of biasLow risk of biasSome concerns
      Mellberg et al., 2014
      • Moradi M
      • Daneshzad E
      • Azadbakht L.
      The effects of isolated soy protein, isolated soy isoflavones and soy protein containing isoflavones on serum lipids in postmenopausal women: A systematic review and meta-analysis.
      Low risk of biasSome concernsLow risk of biasLow risk of biasLow risk of biasSome concerns
      Nowson et al., 2009
      • Liu C
      • Kuang X
      • Li K
      • Guo X
      • Deng Q
      • Li D.
      Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials.
      Some concernsSome concernsLow risk of biasSome concernsLow risk of biasSome concerns
      Buzzard et al., 1990

      Patade A, Devareddy L, Lucas EA, Korlagunta K, Daggy BP, Arjmandi BH. Flaxseed reduces total and LDL cholesterol concentrations in Native American postmenopausal women. Journal of women's health (2002). 2008;17(3):355-66.

      Some concernsSome concernsSome concernsSome concernsLow risk of biasSome concerns
      Thomson et al., 2010
      • Glisic M
      • Kastrati N
      • Musa J
      • Milic J
      • Asllanaj E
      • Portilla Fernandez E
      • et al.
      Phytoestrogen supplementation and body composition in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials.
      Some concernsSome concernsLow risk of biasSome concernsLow risk of biasSome concerns
      Murillo-Ortiz et al., 2017
      • Howard BV
      • Curb JD
      • Eaton CB
      • Kooperberg C
      • Ockene J
      • Kostis JB
      • et al.
      Low-fat dietary pattern and lipoprotein risk factors: The Women's Health Initiative Dietary Modification Trial.
      Some concernsSome concernsLow risk of biasSome concernsLow risk of biasSome concerns
      Table 3Risk of bias in non-randomized trials (ROBINS-I).
      First author, yearRisk of confoundingRisk of selection biasRisk of Misclassification of interventionsRisk of deviation from intended interventionsRisk of missing dataRisk of misclassification of outcomesRisk of reporting biasOverall risk of bias
      Denke, 1994
      • Tinker LF
      • Bonds DE
      • Margolis KL
      • Manson JE
      • Howard BV
      • Larson J
      • et al.
      Low-fat dietary pattern and risk of treated diabetes mellitus in postmenopausal women: The women's health initiative randomized controlled dietary modification trial.
      CriticalLowLowLowLowLowLowCritical
      Kasim-Karakas, 2000
      • Abedi P
      • Huang Soo Lee M
      • Yasin Z
      • Kandiah M
      Diet intervention to improve cardiovascular risk factors among iranian postmenopausal women.
      SeriousLowLowLowModerateLowLowSerious

      3.4 Summary of Evidence

      Due to the nature of the data, limited number of studies, and large heterogeneity among studies, including various designs, population characteristics, and comparisons, we decided to systematically summarize current evidence and to not perform a quantitative meta-analysis. In the following paragraphs, the findings of the included studies are explicated. If available, within and/or between mean changes are reported.

      3.4.1 General/healthy population of postmenopausal women

      Out of 21 trials, 9 reported the effects of diet on lipid profile, glycemic indices, and blood pressure in general/healthy population of postmenopausal women. Among these trials, low-fat diets were the most diet as the intervention and dietary recommendations were used as the most comparisons.
      A cross-over trial assessed the effects of two low-fat diets (low-fat diet and low-fat, high n-3 diet) compared to a high-fat diet in 17 healthy postmenopausal women for 8 weeks. The authors reported no significant differences following the treatment periods compared to the control period for serum insulin levels, FBS, and HOMA (p > 0.05) [
      • Young LR
      • Kurzer MS
      • Thomas W
      • Redmon JB
      • Raatz SK.
      Low-fat diet with omega-3 fatty acids increases plasma insulin-like growth factor concentration in healthy postmenopausal women.
      ]. Additionally, finding of this study on 16 participants demonstrated that the high-fat diet reduced TG level considerably (-35.5 mg/dl, p < 0.05) without any significant between-group differences [
      • McColley SP
      • Georgopoulos A
      • Young LR
      • Kurzer MS
      • Redmon JB
      • Raatz SK.
      A high-fat diet and the threonine-encoding allele (Thr54) polymorphism of fatty acid-binding protein 2 reduce plasma triglyceride-rich lipoproteins.
      ].
      Another cross-over trial observed significant increases for TG (p < 0.001), VLDL (p < 0.05) levels, and TC:HDL (p < 0.002) and a significant decrease in HDL (p < 0.05) concentration following a low-fat, high-carbohydrate diet compared to a high-fat, low-carbohydrates diet after 3 weeks of intervention. No considerable effects were observed on TC and LDL levels in this small sample (n = 10) [
      • Jeppesen J
      • Schaaf P
      • Jones C
      • Zhou MY
      • Ida Chen YD
      • Reaven GM
      Effects of low-fat, high-carbohydrate diets on risk factors for ischemic heart disease in postmenopausal women.
      ].
      A cross-over study on 54 healthy postmenopausal women investigate the effects of a 15 % fat diet compared to 25 and 35% fat diets. This study showed no significant changes in insulin and HbA1c levels while the intervention diet considerably reduced FBS in comparison with the control diets [
      • Kasim-Karakas SE
      • Almario RU
      • Mueller WM
      • Peerson J.
      Changes in plasma lipoproteins during low-fat, high-carbohydrate diets: effects of energy intake.
      ].
      Findings of three sub-studies of 6-year WHI-DM trial are presented in the following paragraphs. This clinical trial aimed at investigating the effects of a reduced-fat diet in comparison to a control group (Dietary Guidelines for Americans) on glycemic indices, lipid profile, and blood pressure. Statistical analysis on 2,263 postmenopausal women without diabetes and cancer showed no significant differences for FBS, insulin sensitivity, and insulin resistance between the intervention and control groups (p > 0.05) [
      • Shikany JM
      • Margolis KL
      • Pettinger M
      • Jackson RD
      • Limacher MC
      • Liu S
      • et al.
      Effects of a low-fat dietary intervention on glucose, insulin, and insulin resistance in the Women's Health Initiative (WHI) dietary modification trial.
      ]. Also, a sub-study by Howard et al. among 2,730 participants, did not find any significant within or between-arms changes in the levels of either TC, LDL, HDL, TG, non-HDL, TC:HDL, and Lp(a) (p > 0.05), when comparing the intervention and control groups [
      • Howard BV
      • Curb JD
      • Eaton CB
      • Kooperberg C
      • Ockene J
      • Kostis JB
      • et al.
      Low-fat dietary pattern and lipoprotein risk factors: The Women's Health Initiative Dietary Modification Trial.
      ]. And Tinker et al. showed the insignificant effect of the intervention on SBP and DBP in (p > 0.05) 45,887 participants as well [
      • Tinker LF
      • Bonds DE
      • Margolis KL
      • Manson JE
      • Howard BV
      • Larson J
      • et al.
      Low-fat dietary pattern and risk of treated diabetes mellitus in postmenopausal women: The women's health initiative randomized controlled dietary modification trial.
      ].
      Another intervention with a low-fat diet compared to general dietary guideline recommendations on 994 participants of Women's Health Trial: Feasibility Study in Minority Populations (WHTFSMP) reported significant reductions in LDL and HDL levels in both intervention and control groups as well as between groups after 12 months (p < 0.05) [
      • Bhargava A.
      Fiber intakes and anthropometric measures are predictors of circulating hormone, triglyceride, and cholesterol concentrations in the women's health trial.
      ]. In addition, according to the findings of this trial reported by Dallas Hall et al. on 1,067 participants no considerable changes in FBS (-0.2 vs -0.1 mmol/L, p > 0.05) and insulin (-0.5 vs 0.3 µlU/mL, p > 0.05) levels after 6 months of intervention compared to the control diet were observed. However, adhering to the low-fat diet showed a significant reduction in SBP compared to the general dietary recommendation, while no significant effect on DBP was reported [
      • Dallas Hall W
      • Feng Z
      • George VA
      • Lewis CE
      • Oberman A
      • Huber M
      • et al.
      Low-fat diet: Effect on athropometrics, blood pressure, glucose, and insulin in older women.
      ]. And neither a high-sodium, high- protein diet nor a low-sodium, usual-protein diet significantly affected DBP or SBP levels in 26 postmenopausal women in a 4-week cross-over trial [
      • Harrington M
      • Bennett T
      • Jakobsen J
      • Ovesen L
      • Brot C
      • Flynn A
      • et al.
      The effect of a high-protein, high-sodium diet on calcium and bone metabolism in postmenopausal women and its interaction with vitamin D receptor genotype.
      ].
      The delta Study, a multicenter 8-week cross-over study, on 18 healthy postmenopausal women compared the effects of two diets (one based on national Cholesterol Education Program (NCEP) and the other one, a low-saturated-fat diet) with the average American dietary intakes. TC, LDL, and HDL concentrations were significantly decreased in both intervention groups in comparison with the control group (p < 0.05) while no considerable differences were observed in TG, Apo B, and TC:HDL levels (p > 0.05). This study also indicated that the low-saturated-fat diet significantly reduced Apo A-1 and increased Lp(a) levels compared to the control group (p < 0.05) [
      • Ginsberg HN
      • Kris-Etherton P
      • Dennis B
      • Elmer PJ
      • Ershow A
      • Lefevre M
      • et al.
      Effects of reducing dietary saturated fatty acids on plasma lipids and lipoproteins in healthy subjects: The delta study, protocol 1.
      ].
      A 6-month intervention on 64 healthy postmenopausal women compared the effects of a healthy diet with habitual dietary intakes. After comparing pre and post-intervention values of this parallel study, significant decreases in serum levels of TC were found in both intervention (-12 mg/dl) and control (-12 mg/dl) groups (p < 0.05) and significant decrease in TG levels was only found in the healthy diet arm (-18.9 mg/dl, p < 0.05). No considerable effect was shown on HDL and LDL concentration (0.40 vs -0.1 mg/dl, -6 vs -7 mg/dl, respectively, p > 0.05) as well as FBS level. However, FBS was significantly decreased within the healthy diet group (-4.5 mg/dl, p < 0.05) [
      • Abedi P
      • Huang Soo Lee M
      • Yasin Z
      • Kandiah M
      Diet intervention to improve cardiovascular risk factors among iranian postmenopausal women.
      ].
      Findings of the Diet and Androgens Randomized Trial (DIANA), an 18-week intervention on 99 healthy postmenopausal women done by Muti et al., showed a considerable reduction of TC level in participants who followed a plant-based diet compared to the control group (-14% vs -4%, p = 0.005). In this study, the control women were not given any specific dietary instruction, they were advised to increase the consumption of fruit and vegetables [
      • Muti P
      • Awad AB
      • Schünemann H
      • Fink CS
      • Hovey K
      • Freudenheim JL
      • et al.
      A Plant Food-Based Diet Modifies the Serum β-Sitosterol Concentration in Hyperandrogenic Postmenopausal Women.
      ]. Also, another report from DIANA study performed by Berrino et al. revealed insignificant effects of this plant-based diet compared to the control group on insulin (-10,6% vs 5.2%, p = 0.72) and FBS (-5.7% vs -1.2%, p = 0.05) levels [
      • Berrino F
      • Bellati C
      • Secreto G
      • Camerini E
      • Pala V.
      Reducing bioavailable sex hormones through a comprehensive change in diet: the diet and androgens (DIANA) randomized trial.
      ].

      3.4.2 Postmenopausal women with cardiovascular risk factors

      Among included studies, 9 trails investigated the effects of diet on the outcomes of interest in postmenopausal women with CVD risk factors, including obesity/overweight, metabolic syndrome, hypertension, and hypercholesterolemia. A variety of diets were intervened in this population, such as fat-modified, energy-restricted, Mediterranean, DASH, and Paleolithic diets.
      A parallel trial assessed the effects of a low-fat, plant-based diet compared to the NCEP recommendation in 59 overweight postmenopausal women. After 14 weeks of intervention, FBS and insulin levels were significantly decreased and insulin sensitivity was increased in the low-fat, plant-based group without any considerable differences with the control group [
      • Barnard ND
      • Scialli AR
      • Turner-McGrievy G
      • Lanou AJ
      • Glass J.
      The effects of a low-fat, plant-based dietary intervention on body weight, metabolism, and insulin sensitivity.
      ].
      Results of a 3-month cross-over trial on 39 postmenopausal women with moderate hypercholesterolemia showed significant decreases in TC (-5%) and LDL (-6%) levels (p < 0.005) within the fat-modified step 1 diet and in comparison with the high-fat, high-saturated diet. Between and within-group changes for VLDL, HDL and TG were not statically considerable (p > 0.05) [
      • Denke MA.
      Individual responsiveness to a cholesterol-lowering diet in postmenopausal women with moderate hypercholesterolemia.
      ].
      Segal-Isaacson et al. showed that both a very low-carbohydrate diet and a low-fat diet resulted in significant decreases of TC, LDL, HDL, and FBS levels (p ≤ 0.05) during 6 weeks follow up in 4 overweight or obese postmenopausal women. The concentration of TG was significantly reduced only in the very low-carbohydrate diet group. Neither of the diets affected the insulin level significantly. No statistically considerable differences between intervention and control groups were observed for any of the outcomes (p > 0.05) [

      Segal-Isaacson CJ, Johnson S, Tomuta V. A randomized trial comparing low-fat and low-carbohydrate diets matched for energy and protein. Obesity …. 2004.

      ].
      Svendsen et al. noted that an energy-restriction diet in postmenopausal women with overweight improved TG, TC, LDL, HDL:LDL, VLDL, and SBP levels in comparison with a usual diet (p < 0.001). No differences were observed for HDL and DBP in 72 women during the 12 weeks follow up period [
      • Svendsen OL
      • Hassager C
      • Christiansen C.
      Effect of an energy-restrictive diet, with or without exercise, on lean tissue mass, resting metabolic rate, cardiovascular risk factors, and bone in overweight postmenopausal women.
      ].
      Findings from Mason et al. in 185 overweight or obese postmenopausal women which investigated the effect of a weight loss diet (providing 1200–2000 kcal/day, and less than 30% of energy intake from fats) compared to the habitual intakes for 12 months indicated the reducing effects of the intervention group compared to the control group for FBS, insulin and HOMA levels [
      • Mason C
      • Foster-Schubert KE
      • Imayama I
      • Kong A
      • Xiao L
      • Bain C
      • et al.
      Dietary weight loss and exercise effects on insulin resistance in postmenopausal women.
      ].
      Se´ne´chal et al. compared the effects of AHA recommendations to habitual dietary intakes on 19 obese postmenopausal women. Twelve weeks of intervention caused significant improvements in TC, TG, LDL, SBP, and DBP levels in the intervention group, while no differences were observed between groups (p > 0.05). Additionally, AHA recommendations led to a significant reduction of HDL levels in comparison with the control group (p ≤ 0.05) and no significant changes were observed with respect to TC:HDL. Also, intervention diet resulted in no significant within or between differences in the levels of insulin, FBS, HOMA, and QUICKI (p > 0.05) [
      • Sénéchal M
      • Bouchard DR
      • Dionne IJ
      • Brochu M.
      The effects of lifestyle interventions in dynapenic-obese postmenopausal women.
      ].
      Findings of a study done by Bajerska et al. in 144 women with metabolic syndrome showed decreases in TG (-33.9 vs -38.8 mg/dl), TC (-15.5 vs -11.2 mg/dl), FBS (-6.4 and -5.4 mg/dl), insulin (-3.5 and -3.1 µU/ml), HOMA (-0.46 and -0.42), DBP (-6.7 and -8.1 mmHg), and SBP (-10.02 and -10.04 mmHg) for either of the Mediterranean diet and Central European diet without any considerable differences between them. Within groups decrease in LDL concentration was noted for women consuming Mediterranean diet (-9.4 mg/dl, p < 0.05) while the women consuming Central European diet showed a decrease in HDL level (-2 mg/dl, p < 0.05) after 16 weeks intervention [

      Bajerska J, Chmurzynska A, Muzsik A. Weight loss and metabolic health effects from energy-restricted Mediterranean and Central-European diets in postmenopausal women: A randomized …: nature.com; 2018.

      ].
      A 24-month parallel comparison between the Paleolithic diet and 4th edition Nordic nutrition recommendations done by Mellberg et al. illustrated the insignificant effects of the Paleolithic diet on TC, LDL, HDL, insulin, FBS, HOMA, and blood pressure levels in 49 obese postmenopausal women in comparison with the control. A significant reduction of TG levels was observed in the intervention group (-0.23 vs -0.01 mmol/L, p = 0.004) compared to the control group [
      • Mellberg C
      • Sandberg S
      • Ryberg M
      • Eriksson M
      • Brage S
      • Larsson C
      • et al.
      Long-term effects of a Palaeolithic-type diet in obese postmenopausal women: A 2-year randomized trial.
      ,
      • Otten J
      • Mellberg C
      • Ryberg M
      • Sandberg S
      • Kullberg J
      • Lindahl B
      • et al.
      Strong and persistent effect on liver fat with a Paleolithic diet during a two-year intervention.
      ].
      Nowson and colleagues compared a vitality diet and a higher acid load healthy diet in 95 women with hypertension followed for 14 weeks. Decreases in SBP (-5.6 mmHg, p < 0.001 and -2.7 mmHg, p < 0.01) and DBP (-4.1 mmHg, p < 0.001, and -2.9 mmHg, p < 0.001) were observed in both groups without any significant differences between groups [
      • Nowson CA
      • Wattanapenpaiboon N
      • Pachett A.
      Low-sodium Dietary Approaches to Stop Hypertension-type diet including lean red meat lowers blood pressure in postmenopausal women.
      ].

      3.4.3 Breast cancer survivors

      The findings of 3 trials in post-menopausal women with breast cancer are presented below. In all 3 trials the effects of a low-fat diet were investigated. Habitual intake, low-carbohydrate diet and American Dietetic Association (ADA) were recommended as the comparisons.
      Findings of a parallel comparison between a low-fat diet and a low-carbohydrate diet in 38 breast cancer survivors demonstrated improvements of TC (-5.2 mg/dl, p = 0.02), LDL (-7.8 mg/dl, p = 0.007), HDL (0.4 mg/dl, p = 0.002) and SBP (−8.6 mmHg, p = 0.03) levels in the low-fat diet group. A considerable within-group decreases in TG (-31.1 mg/dl, p = 0.01), insulin (-2.6 µU/ml, p = 0.002), and HbA1c (-0.1, p = 0.006) was noted in low-carbohydrate arm. The reductions of HOMA in both diets (-1.2, -0.7, p = 0.03) and QUICKI in low-fat diet (p = 0.005) were observed. TC:HDL, FBS, and DBP were not affected considerably by intervention or control arms. No changes were observed between the two groups during a follow up of 24 weeks [
      • Thomson CA
      • Stopeck AT
      • Bea JW
      • Cussler E
      • Nardi E
      • Frey G
      • et al.
      Changes in body weight and metabolic indexes in overweight breast cancer survivors enrolled in a randomized trial of low-fat vs. reduced carbohydrate diets.
      ].
      Also, another parallel clinical trial in which 28 postmenopausal women with breast cancer received either counseling to lower their fat intake or not. After 3 months, TC concentration significantly decreased with 0.48 mmol/L (p < 0.01) in intervention arm and no considerable between groups changes were reported [
      • Buzzard IM
      • Asp EH
      • Chlebowski RT
      • Boyar AP
      • Jeffery RW
      • Nixon DW
      • et al.
      Diet intervention methods to reduce fat intake: nutrient and food group composition of self-selected low-fat diets.
      ].
      Murillo-Ortiz et al. performed a clinical trial investigating the effects of a reduced-fat diet compared to a ADA recommendation on 100 postmenopausal women with breast cancer. After 6 months, a significant decrease in FBS was observed in the intervention group compared to its baseline level (-7.5 mg/dl, p < 0.0001) [
      • Murillo-Ortiz B
      • Martinez-Garza S
      • Landeros VC
      • Velazquez GC
      • Garcia DS.
      Effect of reduced dietary fat on estradiol, adiponectin, and IGF-1 levels in postmenopausal women with breast cancer.
      ].

      4. Discussion

      This systematic review summarizes the available evidence on the effect of whole diets on cardiovascular risk factors in postmenopausal women. We observed that various types of diet have been used in intervention studies in this population, which the majority focused on modified-fat diets. To summarize, some studies showed that fat-modified diets led to improvements of some risk factors such as LDL, TC, SBP, FBS, or Apo A; however, harmful effects on TG, VLDL, Lp(a) and HDL were also observed. Furthermore, some interventions other than fat-modified diets, including the Paleolithic diet, AHA recommendations, a plant-based diet, and energy-restricted or weight-loss diets, found benificial effects on some cardiovascular risk factors such as TG, TC, HDL, insulin, FBS, HOMA compared to the control diets. However, these findings should be interpreted with caution due to the large heterogeneity between intervention diets, comparison groups, intervention durations, and population characteristics. Additionally, some of these findings are based on single studies only.
      Chronic diseases are the leading causes of morbidity and mortality worldwide and aging is one of its greatest risk factors. Additionally, in women, physiological manifestations resulting from menopause could lead to long-term chronic diseases such as CVD [
      • Santoro N
      • Epperson CN
      • Mathews SB.
      Menopausal symptoms and their management.
      ]. Diet has been studied as an modifiable lifestyle factor for cardiometabolic health. Findings of the Brisighella Heart Study, a prospective population-based cohort, are suggestive of protective effects of nutritional education against SBP elevation, hypercholesterolemia, and prevalence of metabolic syndrome related to menopause [
      • Cicero AF
      • Dormi A
      • D'Addato S
      • Gaddi AV
      • Borghi C
      Long-term effect of a dietary education program on postmenopausal cardiovascular risk and metabolic syndrome: the Brisighella Heart Study.
      ]. However, healthy dietary patterns assessed with various diet quality scores (such as DASH, MED, aMED, HEI-2010, MDS, MexD), were not associated with risk of metabolic syndrome in the recent Women's Health Initiative observational prospective cohort study [
      • Santiago-Torres M
      • Shi Z
      • Tinker LF
      • Lampe JW
      • Allison MA
      • Barrington W
      • et al.
      Diet quality indices and risk of metabolic syndrome among postmenopausal women of Mexican ethnic descent in the Women's Health Initiative Observational Study.
      ]. Nonetheless, a higher healthy eating index (HEI-2010) score was significantly associated with lower levels of TG and FBS and higher level of HDL. Moreover, better adherence to the DASH diet was associated with lower glucose levels and higher HDL levels [
      • Santiago-Torres M
      • Shi Z
      • Tinker LF
      • Lampe JW
      • Allison MA
      • Barrington W
      • et al.
      Diet quality indices and risk of metabolic syndrome among postmenopausal women of Mexican ethnic descent in the Women's Health Initiative Observational Study.
      ]. The association of HEI with metabolic risk factors in postmenopausal women were studied by two cross-sectional studies, concluding that inappropriate dietary habits may negatively affect cardiometabolic indicators/ risk factors [
      • Ventura Dde A
      • Fonseca Vde M
      • Ramos EG
      • Marinheiro LP
      • Souza RA
      • Chaves CR
      • et al.
      Association between quality of the diet and cardiometabolic risk factors in postmenopausal women.
      ,
      • Tardivo AP
      • Nahas-Neto J
      • Nahas EA
      • Maesta N
      • Rodrigues MA
      Orsatti FL. Associations between healthy eating patterns and indicators of metabolic risk in postmenopausal women.
      ]. The impacts of diets on cardiovascular health could be defined by different mechanisms. For instance, increasing the consumption of some food groups like whole grains and legumes might improve TC, blood glucose, and insulin due to the high content of soluble fiber [
      • Galisteo M
      • Duarte J
      • Zarzuelo A.
      Effects of dietary fibers on disturbances clustered in the metabolic syndrome.
      ,
      • Jonnalagadda SS
      • Harnack L
      • Liu RH
      • McKeown N
      • Seal C
      • Liu S
      • et al.
      Putting the whole grain puzzle together: health benefits associated with whole grains–summary of American Society for Nutrition 2010 Satellite Symposium.
      ]. Several nutrients such as vitamin C, folic acid, potassium, magnesium, flavonoids, and carotenoids have been suggested to improve endothelial function or to cause vasodilation, which may play a role in the blood pressure lowering effects of fruits and vegetables [
      • Lampe JW.
      Health effects of vegetables and fruit: assessing mechanisms of action in human experimental studies.
      ,
      • Macready AL
      • George TW
      • Chong MF
      • Alimbetov DS
      • Jin Y
      • Vidal A
      • et al.
      Flavonoid-rich fruit and vegetables improve microvascular reactivity and inflammatory status in men at risk of cardiovascular disease–FLAVURS: a randomized controlled trial.
      ]. Higher intake of n-3 fatty acids may result in a reduction of cardiovascular risk factors [
      • Dawczynski C
      • Massey KA
      • Ness C
      • Kiehntopf M
      • Stepanow S
      • Platzer M
      • et al.
      Randomized placebo-controlled intervention with n-3 LC-PUFA-supplemented yoghurt: effects on circulating eicosanoids and cardiovascular risk factors.
      ,
      • Saravanan P
      • Davidson NC
      • Schmidt EB
      • Calder PC.
      Cardiovascular effects of marine omega-3 fatty acids.
      ] and a lower intake of saturated fats may cause a reduction in cardiovascular events [
      • Hooper L
      • Martin N
      • Jimoh OF
      • Kirk C
      • Foster E
      Abdelhamid AS. Reduction in saturated fat intake for cardiovascular disease.
      ]. In this regard, according to a presidential advisory from the American Heart Association, randomized controlled trials that replaced dietary saturated fats intake with polyunsaturated vegetable oils reduced the risk of CVD by about 30%; however, no association was observed when these fats were replaced by refined carbohydrates and sugar. Additionally, in both population-based studies and trials, replacement of saturated fats with unsaturated fats lowered the concentration of LDL, as a cause of atherosclerosis [
      • Sacks FM
      • Lichtenstein AH
      • Wu JHY
      • Appel LJ
      • Creager MA
      • Kris-Etherton PM
      • et al.
      Dietary Fats and Cardiovascular Disease: A Presidential Advisory From the American Heart Association.
      ].
      On a higher level, dietary interventions may be part of larger overall lifestyle interventions. Some studies suggested that lifestyle modification may reduce the risk of diseases such as diabetes and coronary heart diseases and improve cardiovascular risk factors in different populations [
      • Knowler WC
      • Barrett-Connor E
      • Fowler SE
      • Hamman RF
      • Lachin JM
      • Walker EA
      • et al.
      Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.
      ,
      • Toobert DJ
      • Strycker LA
      • Glasgow RE.
      Lifestyle change in women with coronary heart disease: What do we know?.
      ,
      • Tuomilehto J
      • Lindström J
      • Eriksson JG
      • Valle TT
      • Hämäläinen H
      • Ilanne-Parikka P
      • et al.
      Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance.
      ,
      • Salas-Salvadó J
      • Díaz-López A
      • Ruiz-Canela M
      • Basora J
      • Fitó M
      • Corella D
      • et al.
      Effect of a Lifestyle Intervention Program With Energy-Restricted Mediterranean Diet and Exercise on Weight Loss and Cardiovascular Risk Factors: One-Year Results of the PREDIMED-Plus Trial.
      ,
      • Look ARG
      • Wing RR.
      Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: four-year results of the Look AHEAD trial.
      ]. A 6-month clinical trial on postmenopausal women concluded that lifestyle intervention may be also an effective tool for improving cardiovascular risk factors in this population. In this study, exercise, nutrition education, eating behavior self-monitoring, attitudes, and relationships were modified as lifestyle factors [
      • Carels RA
      • Darby LA
      • Cacciapaglia HM
      • Douglass OM.
      Reducing cardiovascular risk factors in postmenopausal women through a lifestyle change intervention.
      ]. Also, a combination of a Mediterranean low-saturated fat diet, stress management, exercise, group support, and smoking cessation improved HbA1c and body composition in postmenopausal women with type 2 diabetes [
      • Toobert DJ
      • Glasgow RE
      • Strycker LA
      • Barrera M
      • Radcliffe JL
      • Wander RC
      • et al.
      Biologic and quality-of-life outcomes from the Mediterranean Lifestyle Program: a randomized clinical trial.
      ].
      Although the beneficial effects of different diets on cardiometabolic health have been established [
      • Siervo M
      • Lara J
      • Chowdhury S
      • Ashor A
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