Menopause and cardiovascular risk: dyslipidemia - role of nutrition and supplementation

Introduction  

Menopause is an important transitional phase in a woman's life, as well as a physiological condition, during which there is a significant decline in the production of estrogen by the ovaries. The reduction in estrogen is associated with a series of physiological changes that can negatively affect a woman's physical fitness and cardiovascular health.  

It is not uncommon in outpatient practice, especially for professionals more accustomed to anthropometric assessments, to find a progressive transition - starting from pre-menopausal age - from a gynoid to an android adiposity, confirmed by the constant increase in the waist/hip ratio. Furthermore, this transition can be empirically associated even with a reduction of the subcutaneous adipose tissue at the gluteofemoral and triceps level , especially in women for whom no changes in weight are recorded in this phase of their life. The change in the woman's shape, to which psychological aspects can be deeply linked , is often associated with a change in her risk profile, cardiovascular but not only.  

In particular, menopause is often accompanied by an increased risk of developing dyslipidemia and other metabolic conditions that predispose to cardiovascular disease. It is well documented that postmenopausal women tend to develop more atherogenic lipid profiles, characterized by increased levels of LDL cholesterol and triglycerides, along with decreased HDL cholesterol.  

Dyslipidemia, defined as an alteration of blood lipid levels (cholesterol, triglycerides and lipoproteins), is a key risk factor for the development of cardiovascular diseases such as atherosclerosis, myocardial infarction and stroke. The management of dyslipidemia is therefore crucial in the primary and secondary prevention of cardiovascular diseases in postmenopausal women. In addition to traditional pharmacological treatments, such as statins, in recent years there has been a growing interest in food supplements with potential nutraceutical effect, able to positively influence lipid metabolism and reduce cardiovascular risk.  

In this context, various natural extracts, including red yeast rice, bergamot and citrus plant extracts , have demonstrated beneficial effects on lipid and glycemic regulation. Let's try to explore in more detail the role of nutrition and supplementation in managing cardiovascular risk in menopause, with a focus on bergamot and citrus extracts , and trying to understand what the contribution of dietary and functional fiber can be in improving the lipid profile.  

Nutritional intervention on these patients should focus on a reduction in the intake of saturated fats and sugars with the diet - and less on the intake of dietary cholesterol, also in light of the new LARN - as well as on an abstention from alcohol. Furthermore, the positive effect of physical activity on increasing HDL values ​​is known. It is understood that nutritional assessment , also aimed at preventing the risk of hypotrophy, sarcopenia and osteopenia / osteoporosis is always an essential step before the development of any nutritional indication.  

 

Menopause and Cardiovascular Risk  

During menopause, the decline in estrogen has a direct impact on cardiovascular risk factors. Estrogen has beneficial effects on the cardiovascular system, including modulation of lipid metabolism and protection against inflammation and oxidative stress. When estrogen levels decline, unfavorable changes in lipid profiles occur . resulting in an increased risk of atherosclerotic plaque formation.  

Dyslipidemias are among the main metabolic conditions that occur during menopause. They therefore include :  

 

  1. Hypercholesterolemia : an increase in total cholesterol and LDL cholesterol, which promote the formation of atherosclerotic plaques and increase the risk of heart attack.  

  1. Lowering HDL Cholesterol : Estrogens promote high levels of HDL, which removes cholesterol from the arteries and transports it to the liver for elimination. During menopause, HDL levels decline, reducing this protective effect.  

  1. Increased triglycerides : Blood triglycerides increase during menopause, contributing to cardiovascular risk.  

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These changes make dyslipidemia control particularly important to reduce cardiovascular risk in postmenopausal women. In addition to drugs, a strategy based on dietary modifications and nutritional supplementation may represent an effective and safe approach.  

 

Nutrition and Dyslipidemia: The Role of Supplements  

In recent years, research has focused on identifying nutraceutical supplements that can help manage dyslipidemia and improve cardiovascular health in postmenopausal women. Among the most studied are red yeast rice extract (containing monacolin K), bergamot extract, and citrus plant extracts . Since monacolin K, which is similar in structure and function to statins, is under investigation for possible adverse effects, bergamot and citrus They have equally adequate mechanisms of action and are equally effective, but have a better safety profile. 
 

Bergamot extract and dyslipidemia  

Bergamot extract (Citrus bergamia ) is rich in flavonoids, especially hesperidin , naringin , and neohesperidin , which are bioactive compounds with powerful antioxidant and anti-inflammatory properties . Several studies have shown that these flavonoids favorably influence lipid metabolism, helping to reduce LDL cholesterol and triglyceride levels and increase HDL cholesterol.  

 

Mechanism of action  

Bergamot acts on lipid metabolism through various mechanisms:  

  1. HMG- CoA reductase inhibition : Like statins, bergamot flavonoids can inhibit the enzyme HMG- CoA reductase, which plays a key role in the synthesis of endogenous cholesterol in the liver. This leads to a reduction in LDL cholesterol levels in the blood.  

  1. Modulation of cholesterol transport : Bergamot appears to enhance the activity of lipoprotein receptors, facilitating the removal of LDL cholesterol from the circulation. It also promotes an increase in HDL cholesterol, thus improving the LDL/HDL ratio, an important indicator of cardiovascular risk.  

  1. Antioxidant and anti-inflammatory effects : Bergamot flavonoids help reduce inflammation and oxidative stress, both critical factors in the development of atherosclerosis. In particular, reducing the oxidation of LDL particles prevents the formation of atherosclerotic plaques.  

 

Scientific evidence  

Several studies conducted on post-menopausal women have now shown that taking bergamot extract for 6 months significantly reduced total cholesterol, LDL cholesterol and triglycerides, with a concomitant improvement in HDL cholesterol. Other studies have confirmed that the effect of bergamot is comparable to that of statins, but without the side effects associated with these drugs, such as myalgia or alterations in liver function.  

Dietary Fiber and Lipid Control  

Dietary fiber is a fundamental tool in the management of dyslipidemia, especially in menopause. There are two main types of fiber: soluble and insoluble, both with beneficial effects on lipid metabolism, but soluble fiber is the most effective in reducing cholesterol levels.  

Mechanism of action  

Dietary fiber works through several mechanisms to improve the lipid profile:  

  1. Reduced cholesterol absorption : Soluble fiber, such as beta -glucan in oats and pectin in apples and citrus fruits, forms a gel in the intestinal tract that traps cholesterol and bile salts, preventing their reabsorption. This stimulates the liver to use circulating cholesterol to produce new bile salts, thereby reducing LDL cholesterol levels.  

  1. Modulation of hepatic lipid production : some types of fiber can positively influence hepatic lipid synthesis, reducing the production of triglycerides and cholesterol. This action is more indirect and mediated by metabolites produced by the microbiota following the intake of fiber with prebiotic properties.  

 

Scientific evidence  

Numerous studies have shown that increased soluble fiber intake is associated with significant reductions in total and LDL cholesterol. For example, a review of several clinical trials found that soluble fiber supplementation can reduce LDL levels by 5-10%, a clinically relevant effect in preventing cardiovascular disease.  

 

Citrus Extract and Blood Sugar Control  

Extracts of plants of the citrus genus , such as bergamot, bitter orange (Citrus aurantium ), and grapefruit, contain several bioactive compounds that have shown beneficial effects not only on lipids, but also on glycemic control, another critical factor in cardiovascular risk, especially in menopause, when insulin resistance tends to increase.  

 

Mechanism of action  

Citrus extracts act on glucose metabolism through several mechanisms:  

  1. Modulation of glucose transporters : Some compounds, such as naringenin , stimulate the activity of the glucose transporter GLUT4, improving glucose uptake into muscle and fat cells, thus reducing postprandial blood glucose levels.  

  1. Reduce Inflammation : Citrus extracts also have powerful anti-inflammatory effects that help reduce systemic inflammation, a contributing factor to insulin resistance and cardiovascular risk.  

Scientific evidence  

Studies in patients with type 2 diabetes have shown that taking a citrus extract significantly reduced blood glucose levels and improved insulin sensitivity. These effects are particularly relevant for postmenopausal women, who often show a greater predisposition to developing alterations in glucose metabolism.  

When to intervene?  

The guidelines of the Italian Society of Cardiology (SIC) , in accordance with European recommendations, offer precise indications on the use of nutraceuticals and statins based on the cardiovascular risk profile and LDL cholesterol levels . These recommendations are based on a stratification of global cardiovascular risk and aim at a personalized approach for the treatment of dyslipidemia. Here is a summary of the main indications:  

1. Cardiovascular risk stratification  

The SIC and the ESC/EAS guidelines ( European Society of Cardiology / European Atherosclerosis Society) divide cardiovascular risk based on various factors, including:  

  • Age  

  • Smoke  

  • Hypertension  

  • LDL Cholesterol  

  • Blood sugar (or presence of diabetes)  

  • Family history of early cardiovascular disease  

Using risk scores, such as SCORE ( Systematic coronary Risk Estimation ), patients are classified into 4 main categories:  

  • Very high risk : presence of established cardiovascular disease, diabetes with organ damage, severe renal insufficiency or LDL ≥190 mg/ dL .  

  • High risk : Patients with multiple risk factors, diabetes without end-organ damage, or LDL between 160-189 mg/ dL .  

  • Moderate risk : patients with LDL 115-159 mg/ dL and few risk factors.  

  • Low risk : LDL <115 mg/ dL and no significant risk factors.  

2. Therapeutic targets for LDL cholesterol  

LDL cholesterol goals vary depending on your risk profile:  

  • Very high risk : LDL target <55 mg/ dL . If the patient has already had cardiovascular events (secondary prevention), the target drops to <40 mg/ dL .  

  • High risk : LDL goal <70 mg/ dL .  

  • Moderate risk : LDL goal <100 mg/ dL .  

  • Low risk : LDL goal <116 mg/ dL .  

3. Use of statins  

Statins are the first-line treatment for LDL cholesterol reduction, especially in high- and very high-risk patients. The main indications include:  

  • Very high and high risk : Statins are recommended as the primary treatment. High-intensity statins, such as atorvastatin or rosuvastatin , are preferred to achieve at least a 50% reduction in LDL. If targets are not achieved with maximally tolerated statin doses, the clinician may add ezetimibe or the new PCSK9 inhibitors.  

  • Moderate risk : Moderate-intensity statins (such as simvastatin ) are recommended to reach LDL goals.  

  • Low risk : Lipid-lowering therapy is considered only if LDL levels exceed recommended limits and lifestyle changes do not help.  

 

4. Use of nutraceuticals  

Nutraceuticals can be used at different stages of treatment, especially for low- or moderate-risk patients or as a complement to statins in patients who do not reach therapeutic targets or do not tolerate statins. The main indications include :  

  • Low-moderate risk : In patients with mild-moderate elevation of LDL cholesterol (between 100-160 mg/ dL ) and in the absence of important risk factors, one can start with lifestyle changes associated with nutraceuticals with a lipid-lowering effect. These include:  

  • Red yeast rice ( monacolin K): Has a similar effect to low-dose statins, but its use is under review due to possible long-term side effects.  

  • Phytosterols : compete with the absorption of cholesterol at intestinal level.  

  • Berberine : works by improving hepatic cholesterol metabolism.  

  • Bergamot extracts : rich in flavonoids, as already mentioned they efficiently reduce LDL and triglycerides.  

  • Soluble fiber : contributes to the reduction of cholesterol through reduced intestinal absorption.  

  • Statin intolerance : In patients who cannot tolerate statins, nutraceuticals can be used as a supportive or replacement therapy. However, their efficacy, although supported by clinical studies, is lower than statins.  

 

5. Therapeutic combinations  

In patients who do not reach LDL cholesterol targets with monotherapy (statins or nutraceuticals), the guidelines suggest combining approaches:  

  • Statins + ezetimibe : to further reduce cholesterol absorption.  

  • Statins + PCSK9 inhibitors : recommended in the most severe cases or for secondary prevention.  

  • Statins + nutraceuticals : in cases where additional LDL reduction is needed or for patients who require lower doses of statins.  

 

6. Risk-based approach  

  • Very high risk : High-intensity statin + ezetimibe /PCSK9 inhibitors to target LDL <55 mg/ dL (or <40 mg/ dL in secondary prevention).  

  • High risk : High-intensity statin to target LDL <70 mg/ dL , with addition of ezetimibe if needed.  

  • Moderate risk : Moderate intensity statins with a goal of LDL <100 mg/ dL . Nutraceuticals may be considered if desired to reduce medication use.  

  • Low risk : Lifestyle modifications are the first line of treatment, followed by nutraceuticals or low-intensity statins if LDL is above recommended limits.  

 

7. Monitoring  

Guidelines recommend regular monitoring of lipid levels to assess treatment effectiveness and patient adherence. Monitoring liver function and side effects is essential for those taking statins or supplements.  

It becomes easy to understand why cooperation between Nutritionist and Doctor is essential to be able to intervene in a productive and safe manner on the patient .  

 

Conclusions  

Statins remain the mainstay of treatment for LDL cholesterol reduction, especially in high- or very high-risk patients . Nutraceuticals , on the other hand, can be used as an option for low- or moderate-risk patients , or as a support in therapeutic combinations or in cases of statin intolerance.  

Menopause is a phase of life that carries an increased risk of cardiovascular disease, largely due to changes in lipid and glucose metabolism associated with the decline in estrogen. Management of dyslipidemia is a crucial aspect of reducing cardiovascular risk, and nutrition, together with nutraceutical supplementation, can play a fundamental role in this management.  

Bergamot and citrus plant extracts , along with dietary fiber, represent promising and safe strategies to improve lipid and glycemic profiles in postmenopausal women. Although further studies are needed to confirm the long-term efficacy of these interventions, current data suggest that supplementation with these extracts may be a useful and well-tolerated option to reduce cardiovascular risk and improve women's quality of life .