Disclaimer: By writing this post, we are not recommending this drug. Some of our readers who were already taking the drug requested that we commission a post on it, and we are providing information that is available in the scientific and clinical literature. Please discuss your medications with your doctor.
What is Lisinopril?
Lisinopril is used to treat high blood pressure, heart failure, and increase survival after having a heart attack. Lisinopril is a drug that belongs to a class called angiotensin-converting-enzyme inhibitors (ACEI) .
Brand names include Zestril, Prinivil, and Qbrelis.
In the 1980s, scientists discovered a snake venom in the poisonous Brazilian viper snake. This led to making the first drugs that would mimic the effects of this snake poison – ACEI. Captopril was the first, and others like lisinopril followed [2, 3].
Mechanism of Action
It all starts with renin cutting angiotensinogen to make angiotensin I. ACE then converts angiotensin I to angiotensin II and breaks down bradykinin, which is used to widen blood vessels and lower blood pressure [6, 7].
Angiotensin II increases blood pressure by narrowing blood vessels and activating kidney cells to release the hormone aldosterone .
In addition, aldosterone retains sodium inside the body. Since water is attracted to high levels of sodium, it also remains in the body, increasing blood volume and blood pressure .
- Directly blocking ACE, which decreases the conversion of angiotensin I to angiotensin II
- Reducing the release of aldosterone, so more sodium and water are flushed from the body
- Reducing the breakdown of bradykinin, which relaxes blood vessels
Overall, lisinopril relaxes blood vessels and helps to remove more salt and water from the body. All other ACE inhibitors have the same mechanism of action. You can recognize if your medication is an ACE inhibitor by its name – they mostly end with “pril”, such as enalapril, captopril, quinapril, perindopril, benazepril, etc.
Uses of Lisinopril
1) Lowers Blood Pressure
In a large study of 24,004 participants with high blood pressure, lisinopril was able to reduce blood pressure. But, its beneficial effects varied more with each checkup compared to other drugs .
Lisinopril (up to 5 mg) reduced blood pressure by ≥ 6 units in a study of 22 children with kidney transplants and was well-tolerated .
2) May Improve Heart Failure
The ATLAS study of 3,164 patients with heart failure assessed the difference between low and high doses of lisinopril (2.5 – 5 mg and 32.5 – 35 mg). Higher doses reduced the risk of death and risk of illness due to heart failure .
3) Improves Chance of Survival After Heart Attacks
Lisinopril (2.5 – 10 mg) decreased the risk of dying by 11% at the end of 6 weeks in a study of 18,895 patients that had suffered from heart attacks .
4) May Improve Kidney Disease
In a study of 18 patients with high blood pressure and kidney problems, lisinopril improved kidney functions independently of dose. In fact, as the dose of lisinopril was gradually reduced over the course of a year, kidney function and blood pressure stayed the same in a third of the patients .
5) May Improve Migraine Headaches
In another study of 21 patients with migraines, lisinopril (5 mg) reduced the frequency of migraine attacks by 50% during the third month of treatment. A cough and dizziness were also reported .
6) May Be An Antioxidant
In a later study of 49 patients who underwent brain surgery, lisinopril acted as an antioxidant given before surgery, reducing harmful compounds in the brain (nitrates and MDA). These effects may help lower the dangerous complications of brain surgery [21, 22].
7) May Help Reduce Colon Cancer
95% of colon cancers arise from the formation of abnormal tissue growth in the colon (so-called adenomatous polyps) .
In a study of 4,660 patients, those who took lisinopril had a 41% lower incidence of advanced abnormal colon growth. Long-term usage may reduce colon cancer development .
8) May Improve Sperm Quality
Low–dose lisinopril (2.5 mg) increased the quantity and quality of sperm cells in one study in about half of the 33 men treated. The participants had normal blood pressure but suffered from infertility, due to semen with a low concentration of sperm .
Lisinopril Side Effects
Lisinopril may cause the following side effects :
- A sore throat or a dry cough – one of the most common side effects
- Low blood pressure
- Confusion, lightheadedness, headache, dizziness, or fainting
- Weakness and fatigue
- Decreased urine volume or concentrating ability
- Nausea, vomiting, or diarrhea
- Severe stomach pain
- Body aches, chills, or fever
- Dark urine or pale stools
- Yellow skin or eyes
A cough develops in 5% to 20% of people who take ACEIs. It is associated with an increased accumulation of inflammatory compounds (bradykinin and substance P), which arises from lisinopril blocking ACE. In such cases, other blood pressure medications are recommended .
People who are allergic to lisinopril or other ACEIs may develop severe swelling (angioedema) of the face, lips, throat, abdomen, or other areas of the body .
Severe swelling (angioedema) of the tongue can be the most life-threatening symptom since it can block the airways. The occurrence of angioedema is low (0.1% – 0.2%), but it gets up to three times higher among Black Americans [30, 31].
Hereditary angioedema has also been reported to be triggered by lisinopril when treating high blood pressure .
Lisinopril can cause serious kidney damage, especially in patients with heart failure. In others with high blood pressure or stents, it may raise markers of kidney damage. Further damage can be prevented by stopping the medication, but sometimes blood tests are needed when lisinopril is started to ensure no damage has occurred .
In a case study, a 52-year-old man with inflammation in his legs was given Lasix (20 mg) and lisinopril (10 mg). When Lasix was increased to 60 mg, very high levels of protein in the urine were present, indicating kidney injury. The study recommends caution when combining diuretics with angiotensin-converting-enzyme inhibitors (ACEIs) .
In another case study, a 51-year old male overdosed with 27 lisinopril (10 mg) tablets over the course of three days and developed sudden kidney injury, acidic blood, severe potassium levels in the blood (hyperkalemia), and destruction of muscle cells (rhabdomyolysis) .
Effects on Blood Lab Markers
Lisinopril may :
- Lower blood glucose
- Increase blood potassium (hyperkalemia)
- Reduce blood sodium (hyponatremia)
- Increase kidney markers (blood urea nitrogen and creatinine)
- Increase liver enzymes and bilirubin
- Slightly are rarely cause anemia, decrease hemoglobin and hematocrit
- Hypothetically low white blood cells and neutrophils (a recorded rare side effect of captopril)
High Blood Potassium Levels (Hyperkalemia)
Hyperkalemia is associated with an increased risk of dying. In one study, a very small amount of people developed high potassium levels, and although rare, the highest occurrence (3.6%) happened mostly in patients taking lisinopril [36, 37].
Low Blood Glucose Levels (Hypoglycemia)
However, the FDA suggests that insulins and other compounds used to treat diabetes may increase the risk of developing dangerously low blood sugar levels when combined with lisinopril, so patients should be monitored especially during the first month of treatment .
Low Blood Cell Count
Low hemoglobin levels point to anemia .
Lisinopril was associated with decreased hemoglobin levels in a study of 701 patients with diabetes and high blood pressure. However, patients with heart failure were more likely to have increased hemoglobin levels .
There was a case of a 67-year-old woman with high blood pressure that was infrequently treated with lisinopril and developed anemia that was later resolved when treatment was discontinued .
In another case, all blood cells were low (pancytopenia) in a 79-year-old woman with high blood pressure during lisinopril and indapamide therapy .
Lisinopril has been used in rat studies to induce anemia .
In a case study of a 56-year-old man, lisinopril caused liver failure and recovered only after stopping treatment .
Pregnancy and Breastfeeding
ACE inhibitors have been associated with increased risk of death and risk of illness in fetuses. Physicians will usually discontinue women from taking an ACE inhibitor, including lisinopril, due to these risks. Other safer alternatives are available .
The birth defects can be debilitating. An 18-year-old pregnant woman who was taking lisinopril for her high blood pressure due to kidney failure (renovascular hypertension) gave birth to a premature baby who had severely damaged kidneys, could not produce urine (anuria), and had a growth delay even after getting a kidney transplant .
In another case, a woman gave birth to a premature baby who had similar symptoms but also developed a serious gut infection (necrotizing enterocolitis) .
It is unknown if lisinopril is safe during breastfeeding as no studies are available on the subject. Therefore, to be safe it should be discontinued if you are taking it and an alternative should be considered. Talk to your doctor or a qualified health practitioner about your options.
Not Safe to Use in Children
The safety and effectiveness of Lisinopril in children below 6 years of age have not been established, but there are studies done by poison control centers that address lisinopril with this age range:
- Out of 691 cases reported to Texas poison control centers, 26 of them (3.8%) had a serious outcome, which involved maximum doses equal to or greater than 80 mg .
- In a 13-year retrospective study of 296 cases reported to the California Poison Control System, the mean total dose ingested by children under 6 years of age was 33.4 mg and only 8 of them experienced low blood pressure .
- Another 10-year study (retrospective) of 384 children under 6 years of age exposed to a single dose of blood-pressure-lowering drugs including lisinopril, only lead to mild poisoning symptoms; hospital evaluation was not a must .
According to the FDA reports, there has been a total of 29 recalls involving lisinopril from 2012 – 2018 mostly due to mislabeling or contamination. Other more serious recalls were filed against some pharmaceutical companies for inadequately investigating customer complaints (a violation of the Current Good Manufacturing Practice).
Nonsteroidal anti-inflammatory drugs (NSAIDs), often used as painkillers, may reduce the effect of lisinopril when taken in combination .
However, not all NSAIDs have the same effects when combined with lisinopril .
In an analysis of 15,841 patients who suffered from heart attacks, aspirin did not increase the risk of harmful events nor did it add to the benefits of lisinopril when taken in combination .
Low Blood Pressure (Hypotension)
According to the FDA, patients with kidney damage, heart failure, or low sodium levels, are more likely to experience low blood pressure from lisinopril. The combined effect of a diuretic may also have additional blood pressure lowering effects, so lisinopril can be reduced to stay at normal levels .
Another case study with a 48-year-old woman saw similar results and improved after discontinuation 
In a study of 10,615 elderly patients treated with lithium, 413 (3.9%) of them reported lithium toxicity. The risk of toxicity increased after treatment with angiotensin-converting-enzyme (ACE) inhibitors .
A patient suffering from alcoholism suffered sudden inflammation of the pancreas (acute pancreatitis) after 3 hours of taking lisinopril .
In another study in rats, lisinopril did not achieve the expected effect (reducing heart enlargement and thickening) when alcohol was used .
Low sodium diets reduced blood pressure more effectively than lisinopril (40 mg) or valsartan (320 mg) in a study (DB-RCT) of 52 patients with kidney disease .
However, in patients with heart failure who have low concentrations of sodium (hyponatremia) in the blood or develop it due to lisinopril, adjustments to a lower dose (2.5 mg) or discontinuation is recommended [33, 73, 74].
Angiotensin-converting-enzyme (ACE) is the main target of lisinopril. Some variations like the presence (I-allele) or absence (D-allele) of a DNA segment within the ACE gene may affect the way it interacts with inhibitors like lisinopril. People that have complete absences of the segment in both parental genes (DD genotype) are more likely to suffer from heart diseases .
However, in a study of 57 patients with kidney transplants, lisinopril was more effective in reducing the enlargement and thickening of the heart in those with DD genotypes .
Other mutations in ACE genes can lead to severe kidney disorders (renal tubular dysgenesis) .
So far, no other genes are affected by lisinopril since it is not metabolized by the body and is only released through flushing by the kidneys .
Initial therapy in patients with high blood pressure is started with 10mg and adjusted up to 40 mg depending on blood pressure response.
Patients with heart failure are started with 5mg and then increase up to 10mg every two weeks depending on response.
Combinations with Other Drugs
Lisinopril is commonly combined with the diuretic hydrochlorothiazide. In a study of 270 patients, the combination reduced blood pressure at two doses (10 and 20 mg). The combination can improve mild to moderate high blood pressure .
Angiotensin Receptor Blockers (ARBs)
In an analysis of 819,491 patients (98% males) with heart disease, lisinopril combined with ARBs reduced the risk of dementia or admission to nursing homes more than lisinopril alone .
In a study of 75 diabetic patients with high blood pressure, lisinopril in combination with candesartan reduced the difference between systolic and diastolic blood pressures (pulse pressure), which is associated with eye, nerve, and kidney problems .
Lisinopril and telmisartan improved memory, inflammation, and oxidative stress in Alzheimer’s dementia mouse models .
Lisinopril (10 mg) and amlodipine (5 mg), in combination with rosuvastatin, reduced blood pressure by 20% and total cholesterol by 32% in a study of 50 patients with high blood pressure and heart disease .
Lisinopril (10 – 20 mg) in combination with simvastatin (20 mg) reduced the same amount of blood pressure as with lisinopril alone in one study .
Lisinopril (40 mg) in combination with lovastatin (20 mg) or pravastatin (10 mg), reduced blood pressure more than lisinopril alone in a study of 35 patients .
Lisinopril (10 – 40 mg) in combination with nebivolol (5 – 20 mg) reduced blood pressure more than each drug did individually in a study of 664 patients with a more severe form of high blood pressure .
In another study, a combination of lisinopril (10 – 40 mg) and carvedilol (20 – 80mg) in patients with moderate to severe high blood pressure, did not show benefits compared each drug alone .
In a study of 25 obese patients, the lisinopril and carvedilol combination was more effective in improving blood vessel health than the combination of lisinopril and hydrochlorothiazide. The combination may lower the risk of developing atherosclerosis [91, 92].
Lisinopril in combination with valsartan reduced blood pressure by relaxing blood vessels, while the combination of lisinopril with carvedilol reduced blood pressure by lowering heart rate .
Lisinopril and natrium diethyldithiocarbamate NDDCT improved memory in rat models of dementia .
Lisinopril (2.5 – 20 mg) reduced the enlargement and thickening of the heart in 36 kidney transplant patients when combined with a drug that reduces the immune response, cyclosporine (100 – 300 mg/mL) .
Other ACE inhibitors
Lisinopril (20 mg) and enalapril (20 mg) equally reduced blood pressure during exercise, at rest, and after 24 hours in a study of 49 males and 9 females with high blood pressure. Another study of 169 patients with high blood pressure showed the dose range of lisinopril (10 to 40 mg) was more effective than enalapril (5 to 20mg) [98, 99].
In a study of 20,252 patients, those who received prescriptions for lisinopril had higher admission rates to the hospital for any reason than those who were given perindopril .
In rat brains, trandolapril was more effective at lower doses than lisinopril but similar outside the brain .
Amlodipine and Chlorthalidone
In a large study of 33,357 participants with high blood pressure, chlorthalidone was more effective in reducing blood pressure than lisinopril or amlodipine .
Taking a different perspective, lisinopril was less effective in preventing stroke among blacks and women than chlorthalidone or amlodipine .
Lisinopril (10 – 40 mg) and atenolol (25 – 100 mg) reduced the enlargement and thickening of the heart in a study of 200 dialysis patients with high blood pressure. There was with no significant difference between the drugs, however, blood pressure, a risk of illness, and hospitalizations for any reason were higher in the lisinopril group .
In a study of 15 patients with high blood pressure, irbesartan (150 to 300 mg) was more effective than lisinopril (10 to 20 mg) at increasing blood vessel flexibility, which is associated with low risk of heart disease .
In a study of 75 Nigerian patients with mild to moderate high blood pressure, the extract Hibiscus sabdariffa and lisinopril (10 mg) reduced blood pressure with no significant difference between the two .
Limitations and Caveats
Angiotensin-converting-enzyme (ACE) inhibitors like lisinopril have been reported to be ineffective in black Americans and more likely to cause an allergic reaction (angioedema) .
Treatment of chronic heart failure with lisinopril in children under 18 has not been studied .
Research is constantly discovering natural compounds that inhibit angiotensin-converting enzyme (ACE), the same way that lisinopril works .
In fact, there is a database of 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 .
The thing is, most of these natural compounds have not been studied in animals, let alone in humans .
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 support heart health and are considered very safe. However, they may further lower your blood pressure, potentially causing it to drop too low.
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.
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 .
- Reducing inflammation
- Improving arterial stiffness
- Lowering cholesterol
- Stimulating the immune system
- Preventing plaque buildup in arteries (atherosclerosis)
Did you know? Cooking garlic can inactive the compounds inside. This means raw garlic is more potent than cooked garlic .
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 .
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 [130, 131].
About 20% of the proteins found in cow’s milk is whey. Human milk contains higher concentrations–around 60% .
Whey protein decreases SBP (top number) by ~4 points and DBP (bottom number) by 2.5 points, based on a clinical trial of 38 people. Other studies have found similar blood pressure lowering effects [136, 137, 138].
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 .
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 .
Casein makes up about 80% of the proteins in cow’s milk. Smaller concentrations are found in human milk .
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 .
Pycnogenol works in several different ways, including ACE inhibition. It also increases nitric oxide, which helps relax blood vessels .
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 .
Another 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 .
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 .
One review analyzed 8 different clinical trials and found that pomegranate juice reduces SBP by 5 points and DBP by 2 points .
Punicic acid, a compound inside pomegranate seed oil, may also prevent plaque buildup in blood vessels (atherosclerosis). A study including 50 people demonstrated that pomegranate seed oil lowers triglyceride levels .
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 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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