Evidence Based

Are There Natural ACE Inhibitors?

Written by Mathew Eng, PharmD | Last updated:
Jonathan Ritter
Puya Yazdi
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology), Puya Yazdi, MD | Written by Mathew Eng, PharmD | Last updated:

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Intermittent Fasting

In recent years, scientists have found numerous natural compounds that potentially work like ACE inhibitors but the research on these compounds is still young. We focus on the 5 with the most amount of clinical studies.

Natural ACE Inhibitors

First, it is important to remember to speak with your physician before taking any natural supplements. Research is constantly discovering natural compounds that show promise in inhibiting angiotensin-converting enzyme (ACE), the same way that lisinopril works [115].

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, like fish, mushrooms, dairy products, meat, and plants, just to name a few [116].

The thing is, most of these natural compounds have not been studied in animals, let alone in humans and hence the majority should be avoided [115].

The following list includes the natural alternatives that have been best studied in clinical trials. Many of these studies focus on blood pressure, specifically the effects on systolic blood pressure (SBP) and diastolic blood pressure (DBP).

All the natural compounds listed below have promising results that support heart health and are considered very safe. However, they may further lower your blood pressure, potentially causing it to drop too low. Additionally, it is important to remember that more clinical trials are needed before we can decide if they can lower blood pressure as well as the ACE inhibitors prescribed by your doctor.

Consult your doctor before supplementing with them. Always talk to your doctor before changing or stopping your medications. It’s also important to let your doctor know of all the supplements and over-the-counter drugs you are currently taking to avoid any potential interactions.

1) Garlic

Research in cells and animals suggests that garlic may act as an ACE inhibitor, similar to lisinopril [117118].

Garlic also acts as an antioxidant, anti-inflammatory, and increases nitric oxide, all of which help with heart health [119120121].

A recent review of 7 clinical trials analyzed garlic’s effect on blood pressure. They found that garlic, on average, reduces both SBP (top number) and DBP (bottom number) by about 7 points [122].

Besides lowering blood pressure, research has uncovered additional heart-protective effects, including [123124125126]:

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

No serious side effects or safety concerns were reported in these studies [124122127].

Did you know? Cooking garlic can inactive the compounds inside. This means raw garlic is more potent than cooked garlic [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, blood clotting, and immune effects [129].

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 [130131].

About 20% of the proteins found in cow’s milk is whey. Human milk contains higher concentrations–around 60% [132].

Various proteins inside whey have demonstrated ACE inhibiting properties [133134135].

Whey protein decreases SBP (top number) by ~4 points and DBP (bottom number) by 2.5 points, based on a small clinical trial of 38 people. Other studies have found similar blood pressure lowering effects [136137138].

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 [139].

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 [140].

Casein makes up about 80% of the proteins in cow’s milk. Smaller concentrations are found in human milk [140].

Research has identified several peptides inside casein that can block ACE [141142].

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 [143].

Another study found that calcium caseinate (one of the compounds inside casein) slightly reduces triglycerides after a meal [144].

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 [145].

Pycnogenol works in several different ways, including ACE inhibition. It also increases nitric oxide, which helps relax blood vessels [146].

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 [147]. Though it is important to remember that many of these trials were sponsored by the manufacturer of the supplement so there is the potential for some 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 improves kidney flow and function in the study[148].

Pycnogenol may also reduce swelling (edema) caused by nifedipine, a blood pressure medication. This effect protects blood vessels from injury and may help patients reduce the dosage of their medications [149].

5) Pomegranate

Pomegranate fruit has several surprising health benefits, including potential heart-protective effects [150].

Both the peel and juice of pomegranate can block ACE activity, much like lisinopril [151152].

One review analyzed 8 different clinical trials and found that pomegranate juice reduces SBP by 5 points and DBP by 2 points [153].

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 [154].

Want More Targeted Ways to Improve Heart Health?

If you’re interested in natural and more targeted ways of improving heart health, we at SelfHacked recommend checking out this cardiovascular wellness report. It gives a genetic-based diet, lifestyle and supplement tips that can help improve your heart health. The recommendations are personalized based on your genes.

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About the Author

Mathew Eng

Mathew Eng

Mathew received his PharmD from the University of Hawaii and an undergraduate degree in Biology from the University of Washington.
Mathew is a licensed pharmacist with clinical experience in oncology, infectious disease, and diabetes management. He has a passion for personalized patient care and believes that education is essential to living a healthy life. His goal is to motivate individuals to find ways to manage their chronic conditions.

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