5 Natural ACE Inhibitors: Health Effects & Limitations

Effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on cardiovascular events and residual renal function in dialysis patients: a meta-analysis of randomised controlled trials

5 Natural ACE Inhibitors: Health Effects & Limitations

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Comparison of the Efficacy and Safety of Different ACE Inhibitors in Patients With Chronic Heart Failure: A PRISMA-Compliant Network Meta-Analysis

5 Natural ACE Inhibitors: Health Effects & Limitations

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5 Natural ACE Inhibitors: Health Effects & Limitations

5 Natural ACE Inhibitors: Health Effects & Limitations

In recent years, scientists have found numerous natural compounds that potentially work ACE inhibitors, a class of blood pressure-lowering drugs, but the research is still young. In this post, we focus on the five with the strongest clinical evidence.

Natural ACE Inhibitors

Please note: remember to speak with your physician before taking any supplements and let them know about all the supplements and over-the-counter drugs you are currently taking. They’re not meant to replace your medical treatment and may interact with certain drugs.

Preliminary research has identified different natural substances that may act as ACE inhibitors, but it doesn’t mean they are effective at reducing blood pressure. Further trials are needed to investigate their health effects.

Research is constantly discovering natural compounds that show promise in inhibiting angiotensin-converting enzyme (ACE), the same way that lisinopril and some other blood pressure-lowering meds work [1].

There is a database of potential natural ACE-inhibiting compounds that includes close to 6,000 entries. These compounds come from a huge variety of sources, fish, mushrooms, dairy products, meat, and plants, to name a few [2].

The thing is, most of these natural compounds have not been studied in animals, let alone in humans and hence can’t be recommended for any health condition [1].

The following list includes the natural alternatives that have been best studied in clinical trials. Many of the studies focus on their effects on blood pressure.

1) Garlic

Research in cells and animals suggests that garlic may act as an ACE inhibitor, similar to lisinopril [3, 4].

Garlic also acts as an antioxidant, anti-inflammatory, and increases nitric oxide, all of which may help with heart health [5, 6, 7].

A recent review of 7 clinical trials analyzed garlic’s effect on blood pressure. They found that garlic, on average, reduces both systolic blood pressure (SBP – top number) and diastolic blood pressure (DBP – bottom number) by about 7 points [8].

Besides lowering blood pressure, research has uncovered additional heart-protective effects, including [9, 10, 11, 12]:

  • Reducing inflammation
  • Improving arterial stiffness
  • Lowering cholesterol
  • Preventing plaque buildup in arteries (atherosclerosis)

Did you know? Cooking garlic can inactive the beneficial compounds. This means raw garlic is more potent [128].

Also, the type of garlic can matter. Aged black garlic has stronger antioxidant effects compared to fresh, raw garlic. On the other hand, aged black garlic has lower anti-inflammatory, anti-blood clotting, and immune effects [13].

2) Whey Protein

Whey is a byproduct of the cheese-making process. It contains a mixture of proteins, vitamins, and minerals. Commonly used as a bodybuilding supplement, whey protein may improve heart health as well [14, 15].

Various proteins inside whey have demonstrated ACE inhibiting properties [16, 17, 18].

Whey protein decreases SBP by ~4 points and DBP by 2.5 points, a small clinical trial of 38 people. Other studies have found similar blood pressure lowering effects [19, 20, 21].

On top of that, a review of 9 clinical trials looked at whey protein’s effect on overweight and obese patients. They found improvements in body weight, cholesterol, and blood pressure, all of which are risk factors for heart disease [22].

3) Casein

Similar to whey protein, casein is a byproduct of cheese production. Casein is also rich in proteins and nutrients, but the amino acids found inside are different from whey [23].

Research has identified several peptides inside casein that can block ACE [24, 25].

One review examined 30 different clinical trials that used casein. On average, it lowered SBP by 3 points and DBP by 1.5. Interestingly, this effect was stronger in Japanese individuals and weaker in Europeans [26].

Another study found that calcium caseinate (one of the compounds inside casein) slightly reduces triglycerides after a meal [27].

4) Pycnogenol

Pycnogenol is the brand name of a supplement made from extracts of the French maritime pine bark. It contains 65-75% procyanidins, compounds with antioxidant and anti-inflammatory effects [28].

Pycnogenol works in several different ways, including ACE inhibition. It also increases nitric oxide, which helps relax blood vessels [29].

A large review of 9 clinical trials analyzed Pycnogenol’s effect on blood pressure. On average, it reduces both SBP and DBP (bottom and top number) by about 3 points. This effect is even greater in those that took supplements for more than 12 weeks [30].

Though it is important to note that many of these trials were sponsored by the manufacturer of the supplement, so there is a potential for bias in these studies.

Another small study of 55 people looked at the effects of Pycnogenol combined with ramipril, an ACE-inhibitor similar to lisinopril. They found that this combination lowers blood pressure better than ramipril alone. The combination also improved kidney flow and function [31].

Pycnogenol may also reduce swelling (edema) caused by nifedipine, a blood pressure-lowering medication. This effect protects blood vessels from injury and may help patients reduce the dosage of their medications [32].

5) Pomegranate

Pomegranate fruit has several surprising health benefits, including potential heart-protective effects [33].

Both the peel and juice of pomegranate can block ACE activity, much lisinopril [34, 35].

One review analyzed 8 clinical trials and found that pomegranate juice reduces SBP by 5 points and DBP by 2 points [36].

Punicic acid, a compound inside pomegranate seed oil, may also prevent plaque buildup in blood vessels (atherosclerosis). A small study of 50 people demonstrated that pomegranate seed oil can lower triglyceride levels [37].

Once again, the above foods and substances are not meant to replace your medical treatment. Taking them in significant amounts may require adjusting the dosage of your medications, which you shouldn’t do on your own. Make sure to speak with your doctor before making any major changes to your day-to-day routine.

Source: https://selfhacked.com/blog/5-natural-ace-inhibitors-with-clinical-trials/

Ramipril: 7 things you should know – Drugs.com

5 Natural ACE Inhibitors: Health Effects & Limitations

Medically reviewed by Carmen Fookes, BPharm Last updated on Dec 29, 2019.

1. How it works

  • Ramipril may be used in the treatment of high blood pressure or heart failure that occurs following a heart attack.
  • Ramipril works by inhibiting an enzyme called angiotensin-converting enzyme (ACE). This enzyme is involved in the production of angiotensin II, a powerful vasoconstrictor (narrows arteries), which also stimulates the release of the hormone aldosterone from the adrenal glands (aldosterone can increase blood pressure). By inhibiting this enzyme, ramipril opens up the arteries (vasodilates) and lowers blood pressure. This also reduces how hard the heart has to work to pump blood around the body, helping to relieve the symptoms of heart failure.
  • Ramipril belongs to a group of medicines known as angiotensin-converting enzyme (ACE) inhibitors.

2. Upsides

  • May be used for the treatment of high blood pressure.
  • Ramipril may also be used to treat heart failure that occurs in stable patients within the first few days of a heart attack.
  • In high blood pressure, ramipril reduces both lying down and standing blood pressure without a significant orthostatic effect (this is the drop in blood pressure that may occur when you go from a sitting to standing position). However, people who become dehydrated while taking ramipril are at higher risk of an orthostatic effect.
  • In people with heart failure, ramipril decreases the size of the heart and increases how much blood the heart can pump out. It also increases exercise tolerance, without having much of an effect on heart rate. Ramipril use can decrease the severity of heart failure, rates of hospitalization and symptoms such as shortness of breath and tiredness. Beneficial effects remain apparent with continued dosing.
  • Effective alone or in combination with other treatments for high blood pressure.
  • Generic ramipril is available.

5. Tips

  • Usually administered once daily; however, your doctor may decide to prescribe it to you twice daily if it appears the effects of ramipril are wearing off quickly. Ensure you are adequately hydrated before starting ramipril. If you are taking ramipril for high blood pressure, continue this medication even if you feel well. High blood pressure does not usually have symptoms.
  • Swallow whole, do not crush or chew. If necessary, open up the contents of the capsule and sprinkle on applesauce or mix with water or apple juice. May be taken with or without food.
  • Treatments that lower blood pressure, such as ramipril, should always be part of a comprehensive cardiovascular risk reduction plan (that also targets, if appropriate, cholesterol lowering, diabetes risk reduction, exercise, weight loss, and smoking cessation).
  • Report any signs of fever or a sore throat to your doctor who may carry out further tests to ensure it is not neutropenia (a decrease in white blood cells). Also report any signs or symptoms of angioedema (swelling of face or throat, difficulty breathing) immediately to your doctor.
  • Your doctor should monitor your blood pressure, kidney function and potassium levels regularly.
  • May cause a fall in blood pressure that may be noticed as light-headedness, especially when you rise from a sitting or lying down position. This usually goes away after a few days of therapy. However, if it persists, call your doctor and ask his/her advice; symptoms usually resolve with continued therapy. Ensure you do not become dehydrated. If you develop excessively low blood pressure, lie down and seek immediate medical attention.
  • Also call your doctor if you develop chest pain, a change in your heartbeat or muscle contraction or weakness.
  • Do not use salt substitutes or supplements containing potassium without first consulting your doctor.
  • Ensure you use adequate contraception or abstain from sex to avoid pregnancy while taking ramipril. If you inadvertently become pregnant while taking ramipril, contact your healthcare provider immediately.
  • If you also have diabetes, you may need to monitor your blood sugar levels more closely during the first few weeks of ramipril therapy.
  • Limit your alcohol intake while taking ramipril because alcohol can further lower your blood pressure and increase the risk of side effects.

6. Response and Effectiveness

  • Peak concentrations of ramipril are reached within an hour of oral administration.
  • Blood pressure lowering effects are seen within an hour of oral administration with peak effects achieved by four to six hours. Blood pressure lowering effects are maintained for at least 24 hours, although in some patients these effects may diminish towards the end of the 24 hour period. It may take several weeks before optimal blood pressure lowering effects are achieved.
  • Abrupt withdrawal of ramipril has not resulted in an abrupt increase in blood pressure; however, as with most antihypertensive drugs, it is best to discontinue ramipril slowly.
  • Studies have shown that ramipril is as effective and well tolerated as enalapril.

Medicines that interact with ramipril may either decrease its effect, affect how long it works for, increase side effects, or have less of an effect when taken with ramipril. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with ramipril include:

  • aliskiren
  • allopurinol (may enhance the potential for allergic reactions)
  • amifostine
  • amphetamines
  • antipsychotic agents (may enhance the blood pressure-lowering effect)
  • aspirin
  • azathioprine
  • diuretics
  • duloxetine
  • ferric gluconate
  • gold injections for arthritis
  • grass pollen allergen extract
  • heparin
  • levodopa
  • lithium
  • NSAIDs, such as ibuprofen, diclofenac, and naproxen
  • other ACE inhibitors (such as captopril or lisinopril) or ARBs (such as candesartan or irbesartan)
  • phosphodiesterase-5-inhibitors, such as sildenafil
  • potassium supplements
  • trimethoprim.

Ramipril may also cause blood sugar levels to drop more than expected when taken with diabetes medication, including insulin. Increased blood sugar monitoring may be required.

Note that this list is not all-inclusive and includes only common medications that may interact with ramipril. You should refer to the prescribing information for ramipril for a complete list of interactions.


Remember, keep this and all other medicines the reach of children, never share your medicines with others, and use ramipril only for the indication prescribed.

Copyright 1996-2020 Drugs.com. Revision date: December 28, 2019.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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Source: https://www.drugs.com/tips/ramipril-patient-tips

Effect of long-term ACE-inhibitor therapy in elderly vascular disease patients

5 Natural ACE Inhibitors: Health Effects & Limitations

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Cardiovascular (CV) disease is the leading cause of death in the elderly. The use of ACE-inhibitors in elderly patients with chronic stable vascular disease has not been previously reported.

The HOPE trial evaluated the effects of ramipril and vitamin E in high-risk vascular disease patients. We report the effects of ramipril in the elderly HOPE study patients, defined as those ≥70 years of age.

A total of 2755 elderly patients with vascular disease or diabetes and at least one additional CV risk factor and without heart failure or low ejection fraction were randomized to ramipril 10 mg daily or placebo. Those assigned to ramipril had fewer major vascular events compared to those assigned to placebo [18.6 vs. 24.0%, hazard ratio (HR) = 0.75, P = 0.0006], CV deaths (9.3 vs. 13.

0%, HR = 0.71, P = 0.003), myocardial infarctions (12.0 vs. 15.6%, HR = 0.75, P = 0.006), and strokes (5.4 vs. 7.7%, HR = 0.69, P = 0.013). Treatment was safe and generally well tolerated.

Ramipril reduces the risk of major vascular events in elderly patients with vascular disease and is safe and well tolerated by most.

Cardiovascular disease, Myocardial infarction, Stroke, Age, ACE-inhibitor

Cardiovascular (CV) diseases account for about 40–50% of all deaths in elderly people in western countries.1 CV risk increases sharply with age and recent guidelines recommend aggressive targeting of aging people for CV risk reduction.

2 However, the elderly have often been excluded from CV randomized controlled trials and few studies have evaluated the effects of various drugs in secondary prevention in these patients.

3 Coupled with the resultant paucity of data on efficacy and safety of CV drugs in elderly patients, there is concern related to their perceived higher risk of adverse drug reactions.

Indeed, elderly subjects have a higher incidence of autonomic dysfunction and are more prone to orthostatic hypotension; their kidney and liver functions are often impaired resulting in reduced excretion rates of drug metabolites and they frequently require drugs for several concomitant illnesses and are thus at risk for drug interactions. Therefore, physicians are often reluctant to use CV preventive drugs in elderly patients.

Angiotensin-Converting Enzyme (ACE) inhibitors have been studied in elderly patients with hypertension, stroke, heart failure, and diabetes.4–6 However, to-date no studies have specifically evaluated the use of ACE-inhibitors in elderly patients with chronic stable vascular disease.

The Heart Outcomes Prevention Evaluation (HOPE) trial showed reduced CV events in high-risk patients with stable vascular disease or with diabetes treated with ramipril.7 We report the efficacy and safety of ramipril in the elderly HOPE patients, those in their 7th and 8th decade of life.


HOPE was a randomized clinical trial, which evaluated the high-tissue affinity ACE-inhibitor ramipril in 9297 high-risk patients with stable vascular disease or diabetes. Detailed descriptions of the HOPE study design have been published.7,8 The current report is a post hoc analysis of the effects of ramipril in elderly patients.

The study complies with the Declaration of Helsinki, was approved by the ethics boards of all participating centres, was monitored by an independent Data Safety and Monitoring Board (DSMB) and all patients provided written informed consent. The authors of this report, the Data Management and Statistical Center and the DSMB were fully independent of the study sponsors.

Study population

Men and women ≥55 years with a history of coronary artery disease (CAD), stroke, peripheral arterial disease (PAD), or with diabetes plus at least one other CV risk factor were enrolled. There was no upper age limit for eligibility. Patients were excluded if they had known heart failure or low left ventricular (LV) ejection fraction (5.

5 mEq/L), myocardial infarction (MI), unstable angina, or stroke within 4 weeks of enrolment, use of or intolerance to ACE-inhibitors or vitamin E or other major life-threatening illnesses. Recruitment occurred from December 1993 to June 1995 in Canada, the USA, Western Europe, and South America.

In this post hoc analysis we defined study patients aged ≥ 70 years as ‘elderly’.

Study design

After a single-blind run-in with ramipril 2.

5 mg for 7–10 days followed by placebo for 10 to 14 days, compliant patients who did not develop side effects were assigned by central concealed randomization to ramipril 10 mg daily or matching placebo and to natural source Vitamin E 400 IU daily or matching placebo in a 2 × 2 factorial design. Ramipril was titrated to 10 mg/day over 1 month, using 2.5 mg/day for the first week and 5 mg/day for 3 weeks thereafter. Median follow-up was 4.4 years (interquartile range, 4.0–4.6 years).

Follow-up and study outcomes

The primary outcome was the composite of CV death, MI, and stroke. Each of the components of this outcome was analysed separately.

Secondary outcomes were all-cause death, revascularizations, and hospitalizations for unstable angina or heart failure, nephropathy and complications related to diabetes.

Additional outcomes included all episodes of heart failure and the development of diabetes. Detailed definitions of these outcomes have been published.7

Statistical analysis

Baseline characteristics were compared using t-tests or chi-square tests, as appropriate. Survival curves were estimated according to the Kaplan–Meier procedure, and treatments were compared by the log-rank test.

All analyses were performed according to the intention-to-treat principle and were stratified for treatment allocation to Vitamin E or placebo to account for the factorial study design. Possible interactions between ramipril and Vitamin E were evaluated.

Cox proportional hazard models were fitted to examine the effect of age using models with a treatment allocation (ramipril or placebo) × age (age groups were defined as those

Source: https://academic.oup.com/eurheartj/article/28/11/1382/2887414

Should Angiotensin-Converting Enzyme Inhibitors Be Continued Over the Long Term in Patients Whose Left Ventricular Ejection Fraction Normalizes After an Episode of Acute Myocarditis? | Revista Española de Cardiología

5 Natural ACE Inhibitors: Health Effects & Limitations

It is well established that long-term administration of angiotensin-converting enzyme (ACE) inhibitors has a favorable effect in patients with chronic heart failure and dilated cardiomyopathy.

However, less information is available on patients whose left ventricular ejection fraction normalizes after an episode of systolic dysfunction secondary to acute myocarditis. We followed 35 patients who were diagnosed at our center between 1987 and 1995 with acute myocarditis and an ejection fraction 50% in all 35 patients.

Treatment with ACE inhibitors was discontinued in 15 of the 35 patients, while the other 20 continued ACE inhibitor therapy. After 3 years of follow-up, no death had occurred, but the incidence of new episodes of heart failure with a left ventricular ejection fraction 50% en los 35 casos.

De esos 35, en 15 se suspendieron los IECA, mientras que 20 continuaron tomándolos.

A los 3 años de seguimiento no hubo ninguna muerte, pero los pacientes en los que se suspendieron los IECA tuvieron una mayor incidencia de nuevos episodios de insuficiencia cardiaca con fracción de eyección < 45% (el 33 frente al 5%; p = 0,064) y menor fracción de eyección (47 ± 12 frente a 57 ± 11%; p = 0,002), lo que indica que estos fármacos se deben mantener a largo plazo también en estos pacientes.


Numerous studies have been performed on the long-term prognosis of patients with chronic heart failure due to left ventricular systolic dysfunction (dilated cardiomyopathy) of different etiology, and much evidence has been collected on the benefits of drugs such as angiotensin converting enzyme inhibitors (ACE inhibitors) and beta-blockers with respect to this prognosis.1 However, the natural history of patients with systolic dysfunction and recently developed heart failure due to acute myocarditis2 is less well known. Neither is it known whether treatment with ACE inhibitors should be maintained over the long term in patients whose left ventricular ejection fraction (LVEF) normalizes after the period of dysfunction. To investigate this, the data for 35 consecutive patients diagnosed at our center between 1987 and 1995 with severe left ventricular systolic dysfunction due to acute myocarditis, and in whom the LVEF normalized after treatment, were reviewed.


The characteristics of the patients, the inclusion criteria, the study protocol, and the results after five years of follow-up have been published elsewhere.2 Clinical, echocardiographic and radioactive isotope criteria were used to arrive at a diagnosis of acute myocarditis, ie, recently developed heart failure (less than two weeks), an LVEF of 50%.

The habitual cardiologists of 15 patients (42%) decided to suspend the use of ACE inhibitors; the remaining 20 patients (58%) continued to take them. The demographic and clinical characteristics of both groups of patients were similar (Table), as was the treatment they received (with the exception of ACE inhibitors).

The LVEF in both eventual groups of patients was similar at the time of release from our center (56 [8] and 57 [8%]), all were asymptomatic, and the prevalence of atrial fibrillation in both was similar (13% and 15%) (Table).

At that moment of release no patient was being treated with diuretics or beta-blockers; digoxin was used for the control of atrial fibrillation in two patients who would eventually no longer receive ACE inhibitors (13%) and in three patients who would continue to receive them (15%).

No patient died during follow-up. However, the incidence of new episodes of heart failure with LVEF

Source: https://www.revespcardiol.org/es-should-angiotensin-converting-enzyme-inhibitors-be/articulo/13096159/