检索问题
哪些食品、功能保健品、补剂或者饮食疗法，可以明确有效的降低血脂。请找影响因子大于5分的文章
根据提供的证据，以下食品、功能保健品、补剂或饮食疗法可以明确有效地降低血脂，且来源文章的影响因子均大于5分：
饮食疗法：
-
地中海饮食 (Mediterranean Diet):
- 富含特级初榨橄榄油或坚果的地中海饮食可以降低主要心血管事件的发生率，这间接说明其对心血管风险因素（包括血脂）的改善作用 。一项针对高心血管风险人群的随机试验显示，补充特级初榨橄榄油或混合坚果的地中海饮食组与对照组相比，主要心血管事件（心肌梗死、中风或心血管原因死亡）的风险比分别为0.70和0.72 。
- 在与低脂纯素饮食的比较中，虽然地中海饮食在降低总胆固醇和低密度脂蛋白胆固醇（LDL-C）方面不如纯素饮食显著，但它能降低收缩压和舒张压，并且在与低脂饮食的长期比较中，能更好地调节内皮功能，这与动脉粥样硬化进展的关键步骤相关 。
- 地中海饮食还能降低2型糖尿病的发生率，即使在不限制卡路里摄入和不改变体力活动的情况下，也能在心血管高风险人群中将糖尿病发生率降低52% 。
- 对于冠心病患者，长期食用富含特级初榨橄榄油的地中海饮食相比低脂饮食，能减缓肾功能下降，尤其在2型糖尿病患者和轻度肾功能受损患者中效果更明显 。
- 此外，地中海饮食对乳腺癌的初级预防也显示出有益效果，特别是补充特级初榨橄榄油的地中海饮食组，与对照组相比，乳腺癌发病率的风险比为0.32 。
-
低脂纯素饮食 (Low-Fat Vegan Diet):
- 一项随机交叉试验发现，低脂纯素饮食在改善体重、血脂浓度和胰岛素敏感性方面优于地中海饮食 。具体而言，纯素饮食组的净体重变化为-6.0 kg，而地中海饮食组为0.0 kg 。
- 在没有药物变化的情况下，纯素饮食组的总胆固醇和LDL-C分别降低了18.7 mg/dL和15.3 mg/dL，而地中海饮食组没有显著变化 。
- 纯素饮食还能改善胰岛素抵抗（HOMA-IR降低）和口服葡萄糖胰岛素敏感性（OGIS增加） 。
-
组合饮食模式 (Portfolio Dietary Pattern):
- 这是一种植物性饮食模式，结合了公认的降胆固醇食物，包括坚果、植物蛋白、粘性纤维和植物固醇 。
- 一项系统回顾和荟萃分析显示，在国家胆固醇教育计划（NCEP）第二步饮食的基础上，组合饮食模式显著降低了LDL-C约17%（平均差-0.73 mmol/L），以及非高密度脂蛋白胆固醇、载脂蛋白B、总胆固醇、甘油三酯、收缩压和舒张压、C反应蛋白，并降低了10年冠心病风险 。
- 组合饮食模式对高密度脂蛋白胆固醇或体重没有影响 。
-
极低卡路里生酮饮食 (Very Low Calorie Ketogenic Diet, VLCKD):
- VLCKD被认为是短期内显著减重和改善超重/肥胖患者多种心血管代谢风险因素的有效策略 。
- 系统回顾和荟萃分析显示，VLCKD与体重减轻-10.0 kg（生酮期长达四周的研究）至-15.6 kg（生酮期至少四周的研究）相关 。
- VLCKD还与BMI、腰围、HbA1c、总胆固醇、甘油三酯以及收缩压和舒张压的显著降低相关 。例如，总胆固醇降低了-28 mg/dl，甘油三酯降低了-30 mg/dl 。
- 研究未发现VLCKD对LDL-C、HDL-C、血清肌酐、血清尿酸和血清钾有变化，但血清钠有所增加 。
-
地中海饮食与肠道微生物代谢的交互作用:
- 一项研究发现，肠道胆汁酸（BA）代谢可以预测心脏代谢风险，并解释个体对地中海饮食干预的反应 。地中海饮食干预引起的BMI降低在12-脱氢胆酸水平较低的个体中更为明显，这表明肠道微生物在调节饮食干预效果中的重要作用 。
功能保健品和补剂：
-
植物甾醇和植物固醇 (Plant Sterols and Stanols):
- 功能性食品中补充的植物甾醇可以降低血胆固醇水平约10-15% 。
- 2019年ESC/EAS血脂异常指南首次推荐植物甾醇作为生活方式干预的辅助措施来降低血胆固醇水平 。
- 然而，也有观点认为植物甾醇本身可能具有致动脉粥样硬化性，需要更多的随机对照试验来调查其对心血管硬终点的影响 。
- 欧洲多学会联合立场文件指出，植物甾醇和植物固醇能有效降低血浆LDL胆固醇水平约5-25% 。
-
红曲米 (Red Yeast Rice) 中的Monacolin K:
- Monacolin K是红曲米中的一种成分，具有降低血脂的潜力 。
- 多学会联合立场文件指出，Monacolin K能有效降低血浆LDL胆固醇水平约5-25% 。
-
小檗碱 (Berberine):
- 小檗碱被认为具有降血脂作用 。
- 与益生菌（尤其是Bifidobacterium pseudocatenulatum）联合治疗时，小檗碱在改善2型糖尿病患者餐后高血脂症方面效果更佳，能降低餐后总胆固醇和LDL-C水平 。这种协同作用与小檗碱激活肠道细菌基因，增强脂肪酸输入和动员有关，从而减少肠道内脂质吸收 。
- 多学会联合立场文件指出，小檗碱能有效降低血浆LDL胆固醇水平约5-25% 。
-
海洋来源的Omega-3脂肪酸 (Marine-derived Omega-3 Fatty Acids):
- 海洋来源的Omega-3脂肪酸，如二十碳五烯酸（EPA）和二十二碳六烯酸（DHA），已被证实具有降低血脂的潜力 。
- 高剂量EPA/DHA补充剂在偏头痛预防方面表现出最高的疗效和可接受性，能显著降低偏头痛频率和严重程度，虽然这并非直接针对血脂，但其广泛的心血管益处与血脂调节相关 。
- 海洋蛋白质、肽、Omega-3脂肪酸、壳聚糖、褐藻糖胶和植物鞣质能改善葡萄糖和脂质代谢，提高胰岛素敏感性，并减少脂肪吸收，具有抗糖尿病和抗高血脂的益处 。
-
大豆蛋白 (Soy Protein):
- 大豆蛋白被认为对血浆脂质水平具有生化效应 。
- 一项针对绝经期女性的系统回顾和荟萃分析显示，植物源性补充剂（特别是来自大豆的植物雌激素）能显著降低总胆固醇、甘油三酯和LDL-C 。
-
绿茶 (Green Tea):
- 绿茶对血浆脂质水平具有生化效应 。
-
益生菌酸奶 (Probiotic Yogurt):
- 益生菌酸奶被认为对血浆脂质水平具有生化效应 。
-
β-葡聚糖 (Beta-glucans):
- 多学会联合立场文件指出，β-葡聚糖能有效降低血浆LDL胆固醇水平约5-25% 。
需要注意的：
- 虽然饱和脂肪曾被广泛建议限制摄入以降低心血管疾病风险，但最新证据表明，胆固醇的总水平可能不如低密度脂蛋白（LDL）颗粒的数量和大小重要 。将饱和脂肪替换为精制碳水化合物（特别是添加糖）可能对心脏健康不利，并可能增加冠心病风险 。因此，饮食指南应将重点从减少饱和脂肪转向减少浓缩糖（尤其是果糖含量高的糖）的摄入 。
- 膳食脂肪对心血管代谢疾病的影响复杂，不同的膳食脂肪及其食物来源对细胞功能、风险因素和临床事件的影响各异 。
- 虽然一些天然保健品如海藻、山楂和大蒜可能对某些患者群体有一定益处，但证据可能有限 。
- 一些被宣传为降血脂的产品，如二十八烷醇、古戈尔甾酮和白藜芦醇，缺乏明确的生化益处证据 。
- 饮食干预和间歇性禁食虽然能改善HDL胆固醇流出能力，但额外增加间歇性禁食并不一定能进一步增强HDL的其他功能，例如PON1和LCAT活性，这需要进一步研究 。
在选择这些疗法时，应遵循医生建议，并与健康专业人员共同制定个性化的饮食和补充方案。
References
1Primary prevention of cardiovascular disease with a Mediterranean diet.PubMed
Ramón Estruch, Emilio Ros, Jordi Salas-Salvadó, et al.
N Engl J Med. 2013 Apr 4;368(14):1279-90. doi: 10.1056/NEJMoa1200303. Epub 2013 Feb 25.
BACKGROUND: Observational cohort studies and a secondary prevention trial have shown an inverse association between adherence to the Mediterranean diet and cardiovascular risk. We conducted a randomized trial of this diet pattern for the primary prevention of cardiovascular events. METHODS: In a multicenter trial in Spain, we randomly assigned participants who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly individual and group educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was the rate of major cardiovascular events (myocardial infarction, stroke, or death from cardiovascular causes). On the basis of the results of an interim analysis, the trial was stopped after a median follow-up of 4.8 years. RESULTS: A total of 7447 persons were enrolled (age range, 55 to 80 years); 57% were women. The two Mediterranean-diet groups had good adherence to the intervention, according to self-reported intake and biomarker analyses. A primary end-point event occurred in 288 participants. The multivariable-adjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.54 to 0.92) and 0.72 (95% CI, 0.54 to 0.96) for the group assigned to a Mediterranean diet with extra-virgin olive oil (96 events) and the group assigned to a Mediterranean diet with nuts (83 events), respectively, versus the control group (109 events). No diet-related adverse effects were reported. CONCLUSIONS: Among persons at high cardiovascular risk, a Mediterranean diet supplemented with extra-virgin olive oil or nuts reduced the incidence of major cardiovascular events. (Funded by the Spanish government's Instituto de Salud Carlos III and others; Controlled-Trials.com number, ISRCTN35739639.).
2A Mediterranean Diet and Low-Fat Vegan Diet to Improve Body Weight and Cardiometabolic Risk Factors: A Randomized, Cross-over Trial.PubMed
Neal D Barnard, Jihad Alwarith, Emilie Rembert, et al.
J Am Nutr Assoc. 2022 Feb;41(2):127-139. doi: 10.1080/07315724.2020.1869625. Epub 2021 Feb 5.
Evidence suggests that both Mediterranean and vegan diets improve body weight and cardiometabolic risk factors, but their relative efficacy has not been compared in a randomized trial. In a randomized crossover trial, 62 overweight adults were randomly assigned to a Mediterranean or vegan diet for a 16-week period. Body weight, plasma lipids, blood pressure, and body composition (dual X-ray absorptiometry) were measured. Secondary measures included insulin resistance (Homeostasis Model Assessment, HOMA-IR), oral glucose insulin sensitivity (OGIS), and predicted insulin sensitivity (PREDIM) indices. Thereafter, participants were asked to return to their baseline diets for 4 weeks, after which they began the opposite diet for 16 weeks. The same parameters were measured before and after this 2 16-week period. Overall net weight changes were 0.0 (Mediterranean) and -6.0 kg (vegan), (treatment effect -6.0 kg [95% CI -7.5 to -4.5]; < 0.001). HOMA-IR decreased and OGIS increased on the vegan diet with no significant change on the Mediterranean diet (treatment effect -0.7 [95% CI, -1.8 to +0.4]; = 0.21; and +35.8 mL/min/m [95% CI, +13.2 to +58.3]; = 0.003, respectively). PREDIM did not change significantly in either group. Among participants with no medication changes, total and LDL-cholesterol decreased 18.7 mg/dL (0.5 mmol/L) and 15.3 mg/dL (0.4 mmol/L), respectively, on the vegan diet, compared with no significant change on the Mediterranean diet (treatment effect -15.6 [-24.6 to -6.6]; = 0.001 and -14.8 [-23.5 to -6.2]; = 0.001, respectively); systolic and diastolic blood pressure decreased 9.3 and 7.3 mmHg on the Mediterranean diet, compared with 3.4 and 4.1 mmHg on the vegan diet (treatment effect +5.9 [95% CI +1.0 to +10.9]; = 0.02; and +1.8 [95% CI -4.6 to +8.1]; = 0.58, respectively). A low-fat vegan diet improved body weight, lipid concentrations, and insulin sensitivity, both from baseline and compared with a Mediterranean diet. Blood pressure decreased on both diets, more on the Mediterranean diet. ClinicalTrials.gov number, NCT03698955 https://clinicaltrials.gov/ct2/show/NCT03698955?term=NCT03698955&draw=2&rank=1.
3Portfolio Dietary Pattern and Cardiovascular Disease: A Systematic Review and Meta-analysis of Controlled Trials.PubMed
Laura Chiavaroli, Stephanie K Nishi, Tauseef A Khan, et al.
Prog Cardiovasc Dis. 2018 May-Jun;61(1):43-53. doi: 10.1016/j.pcad.2018.05.004. Epub 2018 May 26.
BACKGROUND: The evidence for the Portfolio dietary pattern, a plant-based dietary pattern that combines recognized cholesterol-lowering foods (nuts, plant protein, viscous fibre, plant sterols), has not been summarized. OBJECTIVE: To update the European Association for the Study of Diabetes clinical practice guidelines for nutrition therapy, we conducted a systematic review and meta-analysis of controlled trials using GRADE of the effect of the Portfolio dietary pattern on the primary therapeutic lipid target for cardiovascular disease prevention, low-density lipoprotein cholesterol (LDL-C), and other established cardiometabolic risk factors. METHODS: We searched MEDLINE, EMBASE, and The Cochrane Library through April 19, 2018. We included controlled trials ≥ 3-weeks assessing the effect of the Portfolio dietary pattern on cardiometabolic risk factors compared with an energy-matched control diet free of Portfolio dietary pattern components. Two independent reviewers extracted data and assessed risk of bias. The primary outcome was LDL-C. Data were pooled using the generic inverse-variance method and expressed as mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed (Cochran Q statistic) and quantified (I-statistic). GRADE assessed the certainty of the evidence. RESULTS: Eligibility criteria were met by 7 trial comparisons in 439 participants with hyperlipidemia, in which the Portfolio dietary pattern was given on a background of a National Cholesterol Education Program (NCEP) Step II diet. The combination of a portfolio dietary pattern and NCEP Step II diet significantly reduced the primary outcome LDL-C by ~17% (MD, -0.73 mmol/L, [95% CI, -0.89 to -0.56 mmol/L]) as well as non-high-density lipoprotein cholesterol, apolipoprotein B, total cholesterol, triglycerides, systolic and diastolic blood pressure, C-reactive protein, and estimated 10-year coronary heart disease (CHD) risk, compared with an NCEP Step 2 diet alone (p < 0.05). There was no effect on high-density lipoprotein cholesterol or body weight. The certainty of the evidence was high for LDL-cholesterol and most lipid outcomes and moderate for all others outcomes. CONCLUSIONS: Current evidence demonstrates that the Portfolio dietary pattern leads to clinically meaningful improvements in LDL-C as well as other established cardiometabolic risk factors and estimated 10-year CHD risk.
4The Evidence for Saturated Fat and for Sugar Related to Coronary Heart Disease.PubMed
James J DiNicolantonio, Sean C Lucan, James H O'Keefe
Prog Cardiovasc Dis. 2016 Mar-Apr;58(5):464-72. doi: 10.1016/j.pcad.2015.11.006. Epub 2015 Nov 14.
Dietary guidelines continue to recommend restricting intake of saturated fats. This recommendation follows largely from the observation that saturated fats can raise levels of total serum cholesterol (TC), thereby putatively increasing the risk of atherosclerotic coronary heart disease (CHD). However, TC is only modestly associated with CHD, and more important than the total level of cholesterol in the blood may be the number and size of low-density lipoprotein (LDL) particles that contain it. As for saturated fats, these fats are a diverse class of compounds; different fats may have different effects on LDL and on broader CHD risk based on the specific saturated fatty acids (SFAs) they contain. Importantly, though, people eat foods, not isolated fatty acids. Some food sources of SFAs may pose no risk for CHD or possibly even be protective. Advice to reduce saturated fat in the diet without regard to nuances about LDL, SFAs, or dietary sources could actually increase people's risk of CHD. When saturated fats are replaced with refined carbohydrates, and specifically with added sugars (like sucrose or high fructose corn syrup), the end result is not favorable for heart health. Such replacement leads to changes in LDL, high-density lipoprotein (HDL), and triglycerides that may increase the risk of CHD. Additionally, diets high in sugar may induce many other abnormalities associated with elevated CHD risk, including elevated levels of glucose, insulin, and uric acid, impaired glucose tolerance, insulin and leptin resistance, non-alcoholic fatty liver disease, and altered platelet function. A diet high in added sugars has been found to cause a 3-fold increased risk of death due to cardiovascular disease, but sugars, like saturated fats, are a diverse class of compounds. The monosaccharide, fructose, and fructose-containing sweeteners (e.g., sucrose) produce greater degrees of metabolic abnormalities than does glucose (either isolated as a monomer, or in chains as starch) and may present greater risk of CHD. This paper reviews the evidence linking saturated fats and sugars to CHD, and concludes that the latter is more of a problem than the former. Dietary guidelines should shift focus away from reducing saturated fat, and from replacing saturated fat with carbohydrates, specifically when these carbohydrates are refined. To reduce the burden of CHD, guidelines should focus particularly on reducing intake of concentrated sugars, specifically the fructose-containing sugars like sucrose and high-fructose corn syrup in the form of ultra-processed foods and beverages.
5High Dosage Omega-3 Fatty Acids Outperform Existing Pharmacological Options for Migraine Prophylaxis: A Network Meta-Analysis.PubMed
Ping-Tao Tseng, Bing-Yan Zeng, Jiann-Jy Chen, et al.
Adv Nutr. 2024 Feb;15(2):100163. doi: 10.1016/j.advnut.2023.100163. Epub 2023 Dec 16.
Migraine is a highly prevalent neurologic disorder with prevalence rates ranging from 9% to 18% worldwide. Current pharmacologic prophylactic strategies for migraine have limited efficacy and acceptability, with relatively low response rates of 40% to 50% and limited safety profiles. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are considered promising therapeutic agents for migraine prophylaxis. The aim of this network meta-analysis (NMA) was to compare the efficacy and acceptability of various dosages of EPA/DHA and other current Food and Drug Administration-approved or guideline-recommended prophylactic pharmacologic interventions for migraine. Randomized controlled trials (RCTs) were eligible for inclusion if they enrolled participants with a diagnosis of either episodic or chronic migraine. All NMA procedures were conducted under the frequentist model. The primary outcomes assessed were 1) changes in migraine frequency and 2) acceptability (i.e., dropout for any reason). Secondary outcomes included response rates, changes in migraine severity, changes in the frequency of using rescue medications, and frequency of any adverse events. Forty RCTs were included (N = 6616; mean age = 35.0 y; 78.9% women). Our analysis showed that supplementation with high dosage EPA/DHA yields the highest decrease in migraine frequency [standardized mean difference (SMD): -1.36; 95% confidence interval (CI): -2.32, -0.39 compared with placebo] and the largest decrease in migraine severity (SMD: -2.23; 95% CI: -3.17, -1.30 compared with placebo) in all studied interventions. Furthermore, supplementation with high dosage EPA/DHA showed the most favorable acceptability rates (odds ratio: 1.00; 95% CI: 0.06, 17.41 compared with placebo) of all examined prophylactic treatments. This study provides compelling evidence that high dosage EPA/DHA supplementation can be considered a first-choice treatment of migraine prophylaxis because this treatment displayed the highest efficacy and highest acceptability of all studied treatments. This study was registered in PROSPERO as CRD42022319577.
6Efficacy and safety of very low calorie ketogenic diet (VLCKD) in patients with overweight and obesity: A systematic review and meta-analysis.PubMed
Marco Castellana, Eleonora Conte, Angelo Cignarelli, et al.
Rev Endocr Metab Disord. 2020 Mar;21(1):5-16. doi: 10.1007/s11154-019-09514-y.
Very low calorie ketogenic diet (VLCKD) has been proposed as a promising option to achieve a significant weight loss in a short time period. We conducted a systematic review and meta-analysis to evaluate its efficacy and safety in patients with overweight and obesity. Four databases were searched on May 2019. Studies reporting data on body weight, body mass index (BMI), waist circumference, body composition, blood pressure, HbA1c, lipids, and markers of liver and kidney function were selected. Discontinuation was also assessed. Twelve studies were included. VLCKD was associated with weight losses of -10.0 kg (I = 6%) and - 15.6 kg (I = 37%) in studies with a ketogenic phase up to and of at least four weeks, respectively. The weight lost during the ketogenic phase was stable in the subsequent follow-up up to two years (p = 0.12). Also, VLCKD was associated with reductions of BMI (-5.3 kg/m), waist circumference (-12.6 cm), HbA1c (-0.7%), total cholesterol (-28 mg/dl), triglycerides (-30 mg/dl), AST (-7 U/l), ALT (-8 U/l), GGT (-8 U/l), systolic and diastolic blood pressure (-8 and - 7 mmHg, respectively). No changes in LDL cholesterol, HDL cholesterol, serum creatinine, serum uric acid and serum potassium were found. Serum sodium increased during VLCKD (+1.6 mEq/l). The overall prevalence of patients discontinuing VLCKD was 7.5% and this was similar to patients undergoing a low calorie diet (p = 0.83). The present review supports the use of VLCKD as an effective strategy for the management of overweight and obesity. Future guidelines should include a specific recommendation for this intervention.
7Long-term consumption of a mediterranean diet or a low-fat diet on kidney function in coronary heart disease patients: The CORDIOPREV randomized controlled trial.PubMed
Alicia Podadera-Herreros, Juan F Alcala-Diaz, Francisco M Gutierrez-Mariscal, et al.
Clin Nutr. 2022 Feb;41(2):552-559. doi: 10.1016/j.clnu.2021.12.041. Epub 2022 Jan 6.
BACKGROUND & AIMS: Lifestyle and dietary habits influence kidney function, playing an important role in the prevention and development of chronic kidney disease (CKD). The effectiveness of the Mediterranean diet in preserving kidney function has been seen in primary prevention. However, no scientific evidence is currently available to determine which dietary pattern is more effective in the management of CKD in secondary cardiovascular disease prevention. Thus, our aim was to evaluate the efficacy of the long-term consumption of two healthy dietary patterns (a Mediterranean diet rich in extra-virgin olive oil (EVOO) compared to a low-fat diet rich in complex carbohydrates) in preserving kidney function in coronary heart disease (CHD) patients. METHODS: CHD patients (n = 1002) from the CORDIOPREV study were randomized to follow a Mediterranean diet (35% fat, 22% MUFA, <50% carbohydrates) or a low-fat diet (28% fat, 12% MUFA, >55% carbohydrates). Kidney function was assessed by the determination of serum creatinine-based estimated glomerular filtration rate (eGFR) at baseline and after 5-years of dietary intervention. Patients were classified according to their type 2 diabetes (T2DM) status, using baseline eGFR (normal eGFR: ≥ 90 mL/min/1.73 m; mildly-impaired eGFR: 60 to <90 mL/min/1.73 m, severely-impaired eGFR: <60 mL/min/1.73 m) to evaluate its influence on the progression of kidney function. Multiple linear regression analysis were performed to determine the contribution of different clinical and anthropometric parameters to changes in eGFR. RESULTS: Although eGFR declined after both dietary interventions compared to baseline (all p < 0.001), the Mediterranean diet produced a lower decline of eGFR compared to the low-fat diet in patients with T2DM (p = 0.040). This effect was also observed when the overall population was considered (p = 0.033). No significant differences were observed in eGFR between the two diets in non-T2DM patients. In addition, this differential effect of the Mediterranean diet was mainly observed in patients with mildly-impaired eGFR in which this diet slowed eGFR progression (p = 0.002). CONCLUSIONS: The long-term consumption of a Mediterranean diet rich in EVOO, when compared to a low-fat diet, may preserve kidney function, as shown by a reduced decline in eGFR in CHD patients with T2DM. Patients with mildly-impaired eGFR may benefit more from the beneficial effect of the consumption of the Mediterranean diet in preserving kidney function. These findings reinforce the clinical benefits of the Mediterranean diet in the context of secondary cardiovascular disease prevention. CLINICAL TRIAL REGISTRATION: URL, http://www.cordioprev.es/index.php/en. Clinicaltrials.gov number, NCT00924937.
8Combined berberine and probiotic treatment as an effective regimen for improving postprandial hyperlipidemia in type 2 diabetes patients: a double blinded placebo controlled randomized study.PubMed
Shujie Wang, Huahui Ren, Huanzi Zhong, et al.
Gut Microbes. 2022 Jan-Dec;14(1):2003176. doi: 10.1080/19490976.2021.2003176.
Non-fasting lipidemia (nFL), mainly contributed by postprandial lipidemia (PL), has recently been recognized as an important cardiovascular disease (CVD) risk as fasting lipidemia (FL). PL serves as a common feature of dyslipidemia in Type 2 Diabetes (T2D), albeit effective therapies targeting on PL were limited. In this study, we aimed to evaluate whether the therapy combining probiotics (Prob) and berberine (BBR), a proven antidiabetic and hypolipidemic regimen via altering gut microbiome, could effectively reduce PL in T2D and to explore the underlying mechanism. Blood PL (120 min after taking 100 g standard carbohydrate meal) was examined in 365 participants with T2D from the Probiotics and BBR on the Efficacy and Change of Gut Microbiota in Patients with Newly Diagnosed Type 2 Diabetes (PREMOTE study), a random, placebo-controlled, and multicenter clinical trial. Prob+BBR was superior to BBR or Prob alone in improving postprandial total cholesterol (pTC) and low-density lipoprotein cholesterol (pLDLc) levels with decrement of multiple species of postprandial lipidomic metabolites after 3 months follow-up. This effect was linked to the changes of fecal level responding to BBR alone or Prob+BBR treatment. Four genes encoding long-chain acyl-CoA synthetase were identified in the genome of this strain, and transcriptionally activated by BBR. BBR treatment further decreased the concentration of FFA in the culture medium of compared to vehicle. Thus, the activation of by BBR could enhance FFA import and mobilization in and diliminish the intraluminal lipids for absorption to mediate the effect of Prob+BBR on PL. Our study confirmed that BBR and Prob () could exert a synergistic hypolipidemic effect on PL, acting as a gut lipid sink to achieve better lipidemia and CVD risk control in T2D.
9Mediterranean Diet and Invasive Breast Cancer Risk Among Women at High Cardiovascular Risk in the PREDIMED Trial: A Randomized Clinical Trial.PubMed
Estefanía Toledo, Jordi Salas-Salvadó, Carolina Donat-Vargas, et al.
JAMA Intern Med. 2015 Nov;175(11):1752-1760. doi: 10.1001/jamainternmed.2015.4838.
IMPORTANCE: Breast cancer is the leading cause of female cancer burden, and its incidence has increased by more than 20% worldwide since 2008. Some observational studies have suggested that the Mediterranean diet may reduce the risk of breast cancer. OBJECTIVE: To evaluate the effect of 2 interventions with Mediterranean diet vs the advice to follow a low-fat diet (control) on breast cancer incidence. DESIGN, SETTING, AND PARTICIPANTS: The PREDIMED study is a 1:1:1 randomized, single-blind, controlled field trial conducted at primary health care centers in Spain. From 2003 to 2009, 4282 women aged 60 to 80 years and at high cardiovascular disease risk were recruited after invitation by their primary care physicians. INTERVENTIONS: Participants were randomly allocated to a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). MAIN OUTCOMES AND MEASURES: Breast cancer incidence was a prespecified secondary outcome of the trial for women without a prior history of breast cancer (n = 4152). RESULTS: After a median follow-up of 4.8 years, we identified 35 confirmed incident cases of breast cancer. Observed rates (per 1000 person-years) were 1.1 for the Mediterranean diet with extra-virgin olive oil group, 1.8 for the Mediterranean diet with nuts group, and 2.9 for the control group. The multivariable-adjusted hazard ratios vs the control group were 0.32 (95% CI, 0.13-0.79) for the Mediterranean diet with extra-virgin olive oil group and 0.59 (95% CI, 0.26-1.35) for the Mediterranean diet with nuts group. In analyses with yearly cumulative updated dietary exposures, the hazard ratio for each additional 5% of calories from extra-virgin olive oil was 0.72 (95% CI, 0.57-0.90). CONCLUSIONS AND RELEVANCE: This is the first randomized trial finding an effect of a long-term dietary intervention on breast cancer incidence. Our results suggest a beneficial effect of a Mediterranean diet supplemented with extra-virgin olive oil in the primary prevention of breast cancer. These results come from a secondary analysis of a previous trial and are based on few incident cases and, therefore, need to be confirmed in longer-term and larger studies. TRIAL REGISTRATION: ISRCTN.org Identifier: ISRCTN35739639.
10Mediterranean diet and endothelial function in patients with coronary heart disease: An analysis of the CORDIOPREV randomized controlled trial.PubMed
Elena M Yubero-Serrano, Carolina Fernandez-Gandara, Antonio Garcia-Rios, et al.
PLoS Med. 2020 Sep 9;17(9):e1003282. doi: 10.1371/journal.pmed.1003282. eCollection 2020 Sep.
BACKGROUND: Endothelial dysfunction is a crucial step in atherosclerosis development, and its severity is determinant for the risk of cardiovascular recurrence. Diet may be an effective strategy to protect the endothelium, although there is no consensus about the best dietary model. The CORonary Diet Intervention with Olive oil and cardiovascular PREVention (CORDIOPREV) study is an ongoing prospective, randomized, single-blind, controlled trial in 1,002 coronary heart disease (CHD) patients, whose primary objective is to compare the effect of 2 healthy dietary patterns (low-fat versus Mediterranean diet) on the incidence of cardiovascular events. Here, we report the results of one secondary outcome of the CORDIOPREV study: to evaluate the effect of these diets on endothelial function, assessed by flow-mediated dilation (FMD) of the brachial artery. METHODS AND FINDINGS: From the total participants taking part in the CORDIOPREV study, 805 completed endothelial function study at baseline and were randomized to follow a Mediterranean diet (35% fat, 22% monounsaturated fatty acids [MUFAs], and <50% carbohydrates) or a low-fat diet (28% fat, 12% MUFAs, and >55% carbohydrates), with endothelial function measurement repeated after 1 year. As secondary objectives and to explore different underlying mechanisms in the modulation of endothelial function, we quantified endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs) and evaluated, in 24 preselected patients, in vitro cellular processes related to endothelial damage (reactive oxygen species, apoptosis, and senescence) and endothelial repair (cell proliferation and angiogenesis), as well as other modulators (micro-RNAs [miRNAs] and proteins). Patients who followed the Mediterranean diet had higher FMD (3.83%; 95% confidence interval [CI]: 2.91-4.23) compared with those in the low-fat diet (1.16%; 95% CI: 0.80 to 1.98) with a difference between diets of 2.63% (95% CI: 1.89-3.40, p = 0.011), even in those patients with severe endothelial dysfunction. We observed higher EPC levels (group difference: 1.64%; 95% CI: 0.79-2.13, p = 0.028) and lower EMPs (group difference: -755 EMPs/μl; 95% CI: -1,010 to -567, p = 0.015) after the Mediterranean diet compared with the low-fat diet in all patients. We also observed lower intracellular reactive oxygen species (ROS) production (group difference: 11.1; 95% CI: 2.5 to 19.6, p = 0.010), cellular apoptosis (group difference: -20.2; 95% CI: -26.7 to -5.11, p = 0.013) and senescence (18.0; 95% CI: 3.57 to 25.1, p = 0.031), and higher cellular proliferation (group difference: 11.3; 95% CI: 4.51 to 13.5, p = 0.011) and angiogenesis (total master segments length, group difference: 549; 95% CI: 110 to 670, p = 0.022) after the Mediterranean diet than the low-fat diet. Each dietary intervention was associated with distinct changes in the epigenetic and proteomic factors that modulate biological process associated with endothelial dysfunction. The evaluation of endothelial function is a substudy of the CORDIOPREV study. As in any substudy, these results should be treated with caution, such as the potential for false positives because of the exploratory nature of the analyses. CONCLUSIONS: Our results suggest that the Mediterranean diet better modulates endothelial function compared with a low-fat diet and is associated with a better balance of vascular homeostasis in CHD patients, even in those with severe endothelial dysfunction. CLINICAL TRIAL REGISTRATION: URL, http://www.cordioprev.es/index.php/en. clinicaltrials.gov number NCT00924937.
11Effects of dietary interventions and intermittent fasting on HDL function in obese individuals with T2DM: a randomized controlled trial.PubMed
Anja Pammer, Anna Obermayer, Julia T Stadler, et al.
Cardiovasc Diabetol. 2024 Sep 12;23(1):339. doi: 10.1186/s12933-024-02426-5.
BACKGROUND: Cardiovascular disease represents a significant risk factor for mortality in individuals with type 2 diabetes mellitus (T2DM). High-density lipoprotein (HDL) is believed to play a crucial role in maintaining cardiovascular health through its multifaceted atheroprotective effects and its capacity to enhance glycemic control. The impact of dietary interventions and intermittent fasting (IF) on HDL functionality remains uncertain. The objective of this study was to assess the effects of dietary interventions and IF as a strategy to safely improve glycemic control and reduce body weight on functional parameters of HDL in individuals with T2DM. METHODS: Before the 12-week intervention, all participants (n = 41) of the INTERFAST-2 study were standardized to a uniform basal insulin regimen and randomized to an IF or non-IF group. Additionally, all participants were advised to adhere to dietary recommendations that promoted healthy eating patterns. The IF group (n = 19) followed an alternate-day fasting routine, reducing their calorie intake by 75% on fasting days. The participants' glucose levels were continuously monitored. Other parameters were measured following the intervention: Lipoprotein composition and subclass distribution were measured by nuclear magnetic resonance spectroscopy. HDL cholesterol efflux capacity, paraoxonase 1 (PON1) activity, lecithin cholesterol acyltransferase (LCAT) activity, and cholesterol ester transfer protein (CETP) activity were assessed using cell-based assays and commercially available kits. Apolipoprotein M (apoM) levels were determined by ELISA. RESULTS: Following the 12-week intervention, the IF regimen significantly elevated serum apoM levels (p = 0.0144), whereas no increase was observed in the non-IF group (p = 0.9801). ApoM levels correlated with weight loss and fasting glucose levels in the IF group. Both groups exhibited a robust enhancement in HDL cholesterol efflux capacity (p < 0.0001, p = 0.0006) after 12 weeks. Notably, only the non-IF group exhibited significantly elevated activity of PON1 (p = 0.0455) and LCAT (p = 0.0117) following the 12-week intervention. In contrast, the changes observed in the IF group did not reach statistical significance. CONCLUSIONS: A balanced diet combined with meticulous insulin management improves multiple metrics of HDL function. While additional IF increases apoM levels, it does not further enhance other aspects of HDL functionality. TRIAL REGISTRATION: The study was registered at the German Clinical Trial Register (DRKS) on 3 September 2019 under the number DRKS00018070.
12Phytosterols and Cardiovascular Disease.PubMed
Umidakhon Makhmudova, P Christian Schulze, Dieter Lütjohann, et al.
Curr Atheroscler Rep. 2021 Sep 1;23(11):68. doi: 10.1007/s11883-021-00964-x.
PURPOSE OF REVIEW: Coronary heart disease is the leading cause of mortality worldwide. Elevated blood cholesterol levels are not only the major but also the best modifiable cardiovascular risk factor. Lifestyle modifications which include a healthy diet are the cornerstone of lipid-lowering therapy. So-called functional foods supplemented with plant sterols lower blood cholesterol levels by about 10-15%. RECENT FINDINGS: In the recent revision of the ESC/EAS dyslipidemia guideline 2019, plant sterols are recommended for the first time as an adjunct to lifestyle modification to lower blood cholesterol levels. However, the German Cardiac Society (DGK) is more critical of food supplementation with plant sterols and calls for randomized controlled trials investigating hard cardiovascular outcomes. An increasing body of evidence suggests that plant sterols per se are atherogenic. This review discusses this controversy based on findings from in vitro and in vivo studies, clinical trials, and genetic evidence.
13Functional foods and dietary supplements for the management of dyslipidaemia.PubMed
Paola M Hunter, Robert A Hegele
Nat Rev Endocrinol. 2017 May;13(5):278-288. doi: 10.1038/nrendo.2016.210. Epub 2017 Jan 30.
Dyslipidaemia is characterized by increased blood levels of total or LDL cholesterol and triglycerides, or decreased HDL cholesterol levels, and is a risk factor for cardiovascular disease. Dyslipidaemia has a high worldwide prevalence, and many patients are turning to alternatives to pharmacotherapy to manage their lipid levels. Lifestyle modification should be emphasized in all patients to reduce cardiovascular risk and can be initiated before pharmacotherapy in primary prevention of cardiovascular disease. Many functional foods and natural health products have been investigated for potential lipid-lowering properties. Those with good evidence for a biochemical effect on plasma lipid levels include soy protein, green tea, plant sterols, probiotic yogurt, marine-derived omega-3 fatty acids and red yeast rice. Other products such as seaweed, berberine, hawthorn and garlic might confer some limited benefit in certain patient groups. Although none of these products can reduce lipid levels to the same extent as statins, most are safe to use in addition to other lifestyle modifications and pharmacotherapy. Natural health products marketed at individuals with dyslipidaemia, such as policosanol, guggulsterone and resveratrol, have minimal definitive evidence of a biochemical benefit. Additional research is required in this field, which should include large, high-quality randomized controlled trials with long follow-up periods to investigate associations with cardiovascular end points.
14Reduction in the incidence of type 2 diabetes with the Mediterranean diet: results of the PREDIMED-Reus nutrition intervention randomized trial.PubMed
Jordi Salas-Salvadó, Monica Bulló, Nancy Babio, et al.
Diabetes Care. 2011 Jan;34(1):14-9. doi: 10.2337/dc10-1288. Epub 2010 Oct 7.
OBJECTIVE: To test the effects of two Mediterranean diet (MedDiet) interventions versus a low-fat diet on incidence of diabetes. RESEARCH DESIGN AND METHODS: This was a three-arm randomized trial in 418 nondiabetic subjects aged 55-80 years recruited in one center (PREDIMED-Reus, northeastern Spain) of the Prevención con Dieta Mediterránea [PREDIMED] study, a large nutrition intervention trial for primary cardiovascular prevention in individuals at high cardiovascular risk. Participants were randomly assigned to education on a low-fat diet (control group) or to one of two MedDiets, supplemented with either free virgin olive oil (1 liter/week) or nuts (30 g/day). Diets were ad libitum, and no advice on physical activity was given. The main outcome was diabetes incidence diagnosed by the 2009 American Diabetes Association criteria. RESULTS: After a median follow-up of 4.0 years, diabetes incidence was 10.1% (95% CI 5.1-15.1), 11.0% (5.9-16.1), and 17.9% (11.4-24.4) in the MedDiet with olive oil group, the MedDiet with nuts group, and the control group, respectively. Multivariable adjusted hazard ratios of diabetes were 0.49 (0.25-0.97) and 0.48 (0.24-0.96) in the MedDiet supplemented with olive oil and nuts groups, respectively, compared with the control group. When the two MedDiet groups were pooled and compared with the control group, diabetes incidence was reduced by 52% (27-86). In all study arms, increased adherence to the MedDiet was inversely associated with diabetes incidence. Diabetes risk reduction occurred in the absence of significant changes in body weight or physical activity. CONCLUSIONS: MedDiets without calorie restriction seem to be effective in the prevention of diabetes in subjects at high cardiovascular risk.
15Gut microbial metabolism of bile acids modifies the effect of Mediterranean diet interventions on cardiometabolic risk in a randomized controlled trial.PubMed
Peipei Gao, Ehud Rinott, Danyue Dong, et al.
Gut Microbes. 2024 Jan-Dec;16(1):2426610. doi: 10.1080/19490976.2024.2426610. Epub 2024 Nov 13.
Bile acids (BAs) undergo extensive microbial metabolism in the gut and exert hormone-like functions on physiological processes underlying metabolic risk. However, the extent to which gut BA profiles predict cardiometabolic risk and explain individual responses to dietary interventions in humans is still unclear. In the DIRECT-PLUS Trial, we conducted a multi-omics analysis of 284 participants randomized into three groups: healthy dietary guidelines and two Mediterranean diet (MedDiet) groups. We longitudinally measured 44 fecal BAs using liquid chromatography-mass spectrometry, the gut microbiome through shotgun metagenomic sequencing, and body adiposity and serum lipids at baseline, 6, and 18 months. Fecal levels of 14 BAs, such as lithocholic acid and ursodeoxycholic acid, were prospectively associated with body mass index (BMI) and serum lipid profiles (false discovery rate []<0.05). Baseline fecal BA levels significantly modified the beneficial effects of the MedDiet; for example, BMI reduction induced by MedDiet interventions was more pronounced in individuals with lower 12-dehydrocholic acid levels (-interaction <0.001). We confirmed that the gut microbiome is a major modifier of the secondary BA pool in humans. Furthermore, the association of fecal BAs with body adiposity and serum lipids varied significantly in individuals with different abundances of gut microbes carrying BA metabolism enzymes, e.g. several spp. In summary, our study identifies novel predictive biomarkers for cardiometabolic risk and offers new mechanistic insights to guide personalized dietary interventions.
16Plant sterol enriched functional food and atherosclerosis.PubMed
Jürgen Köhler, Daniel Teupser, Albrecht Elsässer, et al.
Br J Pharmacol. 2017 Jun;174(11):1281-1289. doi: 10.1111/bph.13764. Epub 2017 Apr 5.
UNLABELLED: Hypercholesterolaemia is a major cardiovascular risk factor. A healthy diet and a healthy lifestyle reduces cardiovascular risk. 'Functional foods' supplemented with phytosterols are recommended for the management of hypercholesterolaemia and have become a widely used non-prescription approach to lower plasma cholesterol levels. Two billion euros are spent world-wide each year on various functional foods, which have regulator-approved health claims for the management of elevated cholesterol levels. While international societies, such as the European Atherosclerosis Society or the National Heart Foundation in Australia, still advise phytosterols as an additional dietary option in the management of hypercholesterolaemia, recently released guidelines such as those from the National Institute of Health and Clinical Excellence in the United Kingdom are more critical of food supplementation with phytosterols and draw attention to significant safety issues. This review challenges whether an intervention with phytosterol supplements is beneficial. We summarize the current evidence from genetic diseases, genetic association studies, clinical trial data and data from animal studies. LINKED ARTICLES: This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc.
17Effects of Plant-Derived Dietary Supplements on Lipid Profiles in Menopausal Women: An Updated Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.PubMed
Soo-Hyun Park, Mi-Ra Oh, Jangho Lee, et al.
Phytother Res. 2025 Aug;39(8):3486-3507. doi: 10.1002/ptr.8511. Epub 2025 Jul 4.
A Comprehensive evaluation of plant-derived supplements for hypolipidemic effects in menopausal women requires robust clinical trials and integrated analysis of diverse research findings. To address this, we conducted a systematic review and meta - analysis to evaluate the effects of plant-derived supplements on lipid profiles in menopausal women. Relevant studies were identified through systematic searches in MEDLINE, Embase, Web of Science, and CENTRAL until June 2022. Randomized controlled trials assessing the effects of plant-derived supplements on lipid profiles in menopausal women were included. A total of 61 studies were reviewed, and 60 studies with 6127 participants were included in the meta-analysis. Study quality was evaluated using the Cochrane Risk of Bias tool, and pooled data were analyzed with a random effects model for meta-analysis. The analysis revealed significant reductions in total cholesterol (SMD = -0.17, 95% CI: -0.26 to -0.08), triglycerides (SMD = -0.16, 95% CI: -0.26 to -0.05), and LDL-cholesterol (SMD = -0.19, 95% CI: -0.27 to -0.10). Subgroup analysis revealed that phytoestrogens, particularly from soy, were especially effective. Favorable outcomes were also observed in postmenopausal women with amenorrhea for over 1 year and in interventions lasting 3-12 months. However, variations in supplement formulations and insufficient dosage-specific data limited the findings. Further clinical research on plant-derived supplements should be accumulated to clarify their effects. Despite these limitations, this review provides updated evidence and highlights promising materials for improving blood lipid profiles. It also offers insights into optimizing clinical trial designs for dietary supplements, paving the way for more targeted and effective interventions. The study protocol (CRD42022383752) was registered in the PROSPERO database.
18Comprehensive exploration of marine functional foods in modulation of metabolic syndromes: a 20-year review.PubMed
Muhammed Amanat, Shivani Chib, Thakur Gurjeet Singh, et al.
Crit Rev Food Sci Nutr. 2025;65(34):8905-8936. doi: 10.1080/10408398.2025.2513517. Epub 2025 Jun 4.
Metabolic syndromes (MetS), a cluster of conditions threatening global health, are a central focus of medical research. Bioactive compounds from marine sources, including peptides, polysaccharides, and lipids, have shown promising biological activities, such as antioxidant, anti-inflammatory, lipid-lowering, anti-obesity, and insulin-sensitizing effects. These properties hold potential in combating dyslipidemia, nonalcoholic steatohepatitis (NASH), cardiovascular diseases, and diabetes. Present work seeks to review the advancements in research on marine functional foods for treating metabolic disorders over the last 20 years. It focuses on the diverse biological activities of marine-derived compounds, their proposed mechanisms in modulating MetS, and their potential industrial applications in nutraceuticals, pharmaceuticals, functional foods, and cosmeceuticals. As the prevalence of MetS increases, current treatments face challenges like side effects, limited efficacy, and high costs. Considering this, marine functional foods offer a promising alternative due to their rich bioactive compounds, which can target multiple pathways involved in MetS. Moreover, marine proteins, peptides, omega-3 fatty acids, chitosan, fucoidans, and phlorotannins improve glucose and lipid metabolism, enhance insulin sensitivity, and reduce fat absorption, offering anti-diabetic and anti-hyperlipidemic benefits. Despite their potential, challenges like dosage form, purity, encapsulation methods, and stability hinder their broader use.
19Dietary fats and cardiometabolic disease: mechanisms and effects on risk factors and outcomes.PubMed
Jason H Y Wu, Renata Micha, Dariush Mozaffarian
Nat Rev Cardiol. 2019 Oct;16(10):581-601. doi: 10.1038/s41569-019-0206-1.
The effect of dietary fats on cardiometabolic diseases, including cardiovascular diseases and type 2 diabetes mellitus, has generated tremendous interest. Many earlier investigations focused on total fat and conventional fat classes (such as saturated and unsaturated fats) and their influence on a limited number of risk factors. However, dietary fats comprise heterogeneous molecules with diverse structures, and growing research in the past two decades supports correspondingly complex health effects of individual dietary fats. Moreover, health effects of dietary fats might be modified by additional factors, such as accompanying nutrients and food-processing methods, emphasizing the importance of the food sources. Accordingly, the rapidly increasing scientific findings on dietary fats and cardiometabolic diseases have generated debate among scientists, caused confusion for the general public and present challenges for translation into dietary advice and policies. This Review summarizes the evidence on the effects of different dietary fats and their food sources on cell function and on risk factors and clinical events of cardiometabolic diseases. The aim is not to provide an exhaustive review but rather to focus on the most important evidence from randomized controlled trials and prospective cohort studies and to highlight current areas of controversy and the most relevant future research directions for understanding how to improve the prevention and management of cardiometabolic diseases through optimization of dietary fat intake.
20Nutraceuticals and functional foods for the control of plasma cholesterol levels. An intersociety position paper.PubMed
Andrea Poli, Carlo M Barbagallo, Arrigo F G Cicero, et al.
Pharmacol Res. 2018 Aug;134:51-60. doi: 10.1016/j.phrs.2018.05.015. Epub 2018 May 30.
Current evidence shows that cholesterol management either reduces the likelihood of cardiovascular disease (CVD) or slows down its progression. Hence, it is important that all health professionals make appropriate use of all the available intervention strategies to control risk factors: from dietary improvement and positive lifestyle changes to the use of functional foods, food supplements, and drugs. This review examines the effect of the most frequently occurring cholesterol-lowering substances in functional foods or in supplements across Europe, namely plant sterols and stanols, monacolin K found in red yeast rice, berberine and beta-glucans. We conclude that currently available supplements and functional foods can effectively reduce plasma LDL cholesterol levels by about 5 to 25%, either alone or in combination. Suitable candidates for these products are mainly individuals at low absolute cardiovascular risk at a young age or according to classic algorithms. Of note, despite being freely available for purchase, these products should be used following shared agreement between the physician and the patient ("concordance").