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# These authors contributed equally in this systematic review.
Anniek C. van Westing
Footnotes
# These authors contributed equally in this systematic review.
Affiliations
Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The NetherlandsDivision of Human Nutrition and Health, Wageningen University and Research, Wageningen, The Netherlands
Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, IranNutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The NetherlandsDivision of Human Nutrition and Health, Wageningen University and Research, Wageningen, The Netherlands
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.
]. 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 [
The Relative Burden of Menopausal and Postmenopausal Symptoms versus Other Major Conditions: A Retrospective Analysis of the Medical Expenditure Panel Survey Data.
]. 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 [
]. In women, it has been suggested that the dietary intakes are also associated with menopausal symptoms severity, although the findings are inconsistent and inconclusive [
So far, the majority of studies have investigated the effects of supplements, nutrients, or isolated single foods on menopausal health issues in postmenopausal women [
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.
Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials.
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.
] 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 [
Low-fat dietary pattern and risk of treated diabetes mellitus in postmenopausal women: The women's health initiative randomized controlled dietary modification trial.
]. 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 [
]. 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 [
]. 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 [
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 [
The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.
]. 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) [
]. 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 [
Dietary intervention to reduce fat intake does not result in lower incident carotid artery disease: the women's health initiative diet modification trial.
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.
Glucose regulation during weight loss under dissociation of negative energy balance and changed body composition: preliminary data from an ongoing randomized controlled trial.
A high carbohydrate, low fat, hypocaloric eating pattern using functional foods along with increased physical activity in postmenopausal women decreases cardiovascular risk factors.
Journal of the american dietetic association.2004; 104: 31
Diet quality following meal replacement vs food-based weight loss diets in postmenopausal women with obesity: a secondary analysis of TheTEMPO Diet Trial.
Boers I, Muskiet FAJ, Berkelaar E, Schut E. Favourable effects of consuming a Palaeolithic-type diet on characteristics of the metabolic syndrome: a randomized controlled pilot-study: Springer; 2014.
Intake of a diet high in trans monounsaturated fatty acids or saturated fatty acids. Effects on postprandial insulinemia and glycemia in obese patients with NIDDM.
Effects of diet composition on weight loss, metabolic factors and biomarkers in a 1-year weight loss intervention in obese women examined by baseline insulin resistance status.
Serum antioxidant capacity, biochemical profile and body composition of breast cancer survivors in a randomized Mediterranean dietary intervention study.
Short- and long-term effects of continuous versus intermittent restrictive diet approaches on body composition and the metabolic profile in overweight and obese postmenopausal women: A pilot study.
Azadbakht L, Kimiagar M, Mehrabi Y. Soy inclusion in the diet improves features of the metabolic syndrome: a randomized crossover study in postmenopausal women. … American journal of …. 2007.
Exercise attenuates the increase in plasma monounsaturated fatty acids and high-density lipoprotein cholesterol but not high-density lipoprotein 2b cholesterol caused by high-oleic ground beef in women.
Effects on plasma lipoproteins and endogenous sex hormones of substituting lean white fish for other animal-protein sources in diets of postmenopausal women.
American journal of clinical nutrition.1992; 55: 896-901
Lifestyle intervention and coronary heart disease risk factor changes over 18 months in postmenopausal women: The women on the move through activity and nutrition (WOMAN study) clinical trial.
Structured hypocaloric diet is more effective than behavioral therapy in reducing metabolic syndrome in Mexican postmenopausal women: A randomized controlled trial.
Effect of dietary patterns differing in carbohydrate and fat content on blood lipid and glucose profiles based on weight-loss success of breast-cancer survivors.
Toobert DJ, Glasgow RE, Strycker LA, Barrera M. Biologic and quality-of-life outcomes from the Mediterranean Lifestyle Program: a randomized clinical trial. Diabetes …. 2003.
Low-fat dietary pattern and risk of treated diabetes mellitus in postmenopausal women: The women's health initiative randomized controlled dietary modification trial.
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.
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.
Segal-Isaacson CJ, Johnson S, Tomuta V. A randomized trial comparing low-fat and low-carbohydrate diets matched for energy and protein. Obesity …. 2004.
Changes in body weight and metabolic indexes in overweight breast cancer survivors enrolled in a randomized trial of low-fat vs. reduced carbohydrate diets.
Effects of a low-fat dietary intervention on glucose, insulin, and insulin resistance in the Women's Health Initiative (WHI) dietary modification trial.
Fiber intakes and anthropometric measures are predictors of circulating hormone, triglyceride, and cholesterol concentrations in the women's health trial.
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.
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.
Segal-Isaacson CJ, Johnson S, Tomuta V. A randomized trial comparing low-fat and low-carbohydrate diets matched for energy and protein. Obesity …. 2004.
Changes in body weight and metabolic indexes in overweight breast cancer survivors enrolled in a randomized trial of low-fat vs. reduced carbohydrate diets.
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.
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.
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.
Segal-Isaacson CJ, Johnson S, Tomuta V. A randomized trial comparing low-fat and low-carbohydrate diets matched for energy and protein. Obesity …. 2004.
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.
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.
Changes in body weight and metabolic indexes in overweight breast cancer survivors enrolled in a randomized trial of low-fat vs. reduced carbohydrate diets.
Changes in body weight and metabolic indexes in overweight breast cancer survivors enrolled in a randomized trial of low-fat vs. reduced carbohydrate diets.
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.
Segal-Isaacson CJ, Johnson S, Tomuta V. A randomized trial comparing low-fat and low-carbohydrate diets matched for energy and protein. Obesity …. 2004.
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.
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.
Segal-Isaacson CJ, Johnson S, Tomuta V. A randomized trial comparing low-fat and low-carbohydrate diets matched for energy and protein. Obesity …. 2004.
]. 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.
Segal-Isaacson CJ, Johnson S, Tomuta V. A randomized trial comparing low-fat and low-carbohydrate diets matched for energy and protein. Obesity …. 2004.
]. 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 [
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.
Changes in body weight and metabolic indexes in overweight breast cancer survivors enrolled in a randomized trial of low-fat vs. reduced carbohydrate diets.
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.
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.
Segal-Isaacson CJ, Johnson S, Tomuta V. A randomized trial comparing low-fat and low-carbohydrate diets matched for energy and protein. Obesity …. 2004.
The Relative Burden of Menopausal and Postmenopausal Symptoms versus Other Major Conditions: A Retrospective Analysis of the Medical Expenditure Panel Survey Data.
Healthy 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/day
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.
Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials.
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.
Low-fat dietary pattern and risk of treated diabetes mellitus in postmenopausal women: The women's health initiative randomized controlled dietary modification trial.
Central 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)
The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.
Low-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 cereals
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.
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 [
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.
The Relative Burden of Menopausal and Postmenopausal Symptoms versus Other Major Conditions: A Retrospective Analysis of the Medical Expenditure Panel Survey Data.
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.
Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials.
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.
Low-fat dietary pattern and risk of treated diabetes mellitus in postmenopausal women: The women's health initiative randomized controlled dietary modification trial.
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) [
]. 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 [
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) [
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 [
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) [
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 [
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) [
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 [
]. 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 [
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) [
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) [
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 [
]. 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 [
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 [
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) [
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 [
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 [
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) [
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 [
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 [
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 [
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 [
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) [
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 [
]. 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 [
]. 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 [
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 [
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 [
]. 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 [
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 [
Flavonoid-rich fruit and vegetables improve microvascular reactivity and inflammatory status in men at risk of cardiovascular disease–FLAVURS: a randomized controlled trial.
]. 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 [
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 [
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.
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 [
]. 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 [
Effect of the ketogenic diet on glycemic control, insulin resistance, and lipid metabolism in patients with T2DM: a systematic review and meta-analysis.
The effect of paleolithic diet on glucose metabolism and lipid profile among patients with metabolic disorders: a systematic review and meta-analysis of randomized controlled trials.
], this study shows inconsistent findings and lack of high-quality information on the effects of whole diets on cardiovascular risk factors specifically in postmenopausal women. Some of the included trials have shown benefits of diet on some lipid profile makers, glycemic indices, and blood pressure 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.
Segal-Isaacson CJ, Johnson S, Tomuta V. A randomized trial comparing low-fat and low-carbohydrate diets matched for energy and protein. Obesity …. 2004.
Changes in body weight and metabolic indexes in overweight breast cancer survivors enrolled in a randomized trial of low-fat vs. reduced carbohydrate diets.
Fiber intakes and anthropometric measures are predictors of circulating hormone, triglyceride, and cholesterol concentrations in the women's health trial.
Low-fat dietary pattern and risk of treated diabetes mellitus in postmenopausal women: The women's health initiative randomized controlled dietary modification trial.
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.
Effects of a low-fat dietary intervention on glucose, insulin, and insulin resistance in the Women's Health Initiative (WHI) dietary modification trial.
] and the majority of them did not find any considerable differences between the intervention diets and the controls. Underrepresentation of the elderly population and women in cardiovascular clinical trials has been discussed for several years [
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