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Hydrochlorothiazide: Side Effects & Possible Alternatives

Written by Carlos Tello, PhD (Molecular Biology) | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:
Jonathan Ritter
Puya Yazdi
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology), Puya Yazdi, MD | Written by Carlos Tello, PhD (Molecular Biology) | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:

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Unfortunately, the commonly prescribed diuretic hydrochlorothiazide can disturb electrolytes, uric acid, sugars, and fats in the blood. For this reason, a lot of people with mild symptoms turn to natural diuretics. Read on to learn more, including a breakdown of the best natural alternatives and how effective they are.

Disclaimer: By writing this post, we are not recommending this drug. Some of our readers requested that we commission a post on it and we are providing a summary of the information available in the scientific and clinical literature, along with a list of evidence-based natural alternatives. Please discuss your medications with your doctor.

What Is Hydrochlorothiazide?

Hydrochlorothiazide is a diuretic mainly used for high blood pressure and water retention. It belongs to the class of thiazide diuretics (or benzothiadiazines). Thiazide diuretics promote the flushing of sodium and water in urine by blocking sodium uptake in the kidneys [1, 2, 3].

Hydrochlorothiazide has become the most commonly prescribed drug for high blood pressure since it was launched in 1959. In 2008, almost 48 million prescriptions for hydrochlorothiazide alone and over 87 million for its combination with other drugs were written in the US. Of these, 97% were for low-dose (12.5 or 25 mg/day) hydrochlorothiazide [4].

Hydrochlorothiazide is approved by the FDA for treating [1]:

  • High blood pressure
  • Water retention (edema) due to kidney failure, heart failure, liver damage (cirrhosis), and corticosteroid or estrogen therapy

Although not approved by the FDA, doctors may prescribe hydrochlorothiazide for the following conditions [2]:

  • Kidney stones
  • Diabetes insipidus
  • Osteoporosis
  • Ménière’s disease, a disorder of the inner ear
  • Acid buildup in the body from kidney dysfunction (renal tubular acidosis)

An important drawback of thiazide diuretics is an increased potassium excretion, which may alter the heart rate and cause serious complications. Their combination with potassium-sparing diuretics (triamterene, amiloride, spironolactone) can prevent this adverse effect [5].

For more about hydrochlorothiazide, how it works, and what it’s prescribed for, check out this post.

Hydrochlorothiazide is a commonly prescribed diuretic drug which promotes the flushing of sodium and water in the urine. It is approved for high blood pressure and edema, and it has a handful of off-label uses.

Side Effects

Hydrochlorothiazide may cause different side effects. Consult your doctor if these effects are severe or mild but persistent and carefully follow their recommendations.

1) May Cause Potassium Deficits

Potassium deficits are a well-known consequence of diuretics, especially in older people. Mild potassium deficits normally don’t cause symptoms but severe deficiency can cause [6, 7]:

  • Weakness
  • Muscle pain and cramps
  • Irregular heart rate
  • Seizures
  • Constipation and reduced urine production
  • Disturbed blood sugar balance
  • Increased thirst and dry mouth

Potassium deficits are more common in women and increase the risk of heart disease. Hydrochlorothiazide was associated with potassium deficits in observational studies on over 36,000 people with high blood pressure [8, 9, 10, 11].

Potassium deficits can be compensated by taking potassium salts. In 3 clinical trials on 55 people on hydrochlorothiazide, potassium-magnesium-citrate prevented potassium deficits (unlike potassium chloride) [12, 6, 13].

Another option is combining hydrochlorothiazide with potassium-sparing diuretics such as:

  • Triamterene [14, 15, 16]
  • Amiloride [17, 18]
  • Spironolactone [19]
In addition to sodium and water, hydrochlorothiazide promotes the excretion of potassium, which may result in dangerous potassium deficits. Taking potassium salts can reverse this side effect.

2) May Increase Blood Uric Acid

Hydrochlorothiazide can raise blood uric acid levels, which is linked to an increased risk of [20, 21, 22]:

  • Gout [23]
  • High blood pressure [24]
  • Diabetes and obesity [25, 26, 27]
  • Heart disease [28]

Hydrochlorothiazide was associated with an increased risk of gout in studies on over 12,000 people [29, 30, 31].

Normal blood uric acid levels are conventionally restored by combining hydrochlorothiazide with other drugs (aspirin, probenecid, sulfinpyrazone, and losartan) [21, 32, 33, 34].

3) May Increase Blood Calcium Levels

Very high blood calcium can cause [35]:

  • Nausea, vomiting, stomach pain
  • Excessive thirst
  • Muscle weakness and fatigue
  • Numbness and confusion

High blood calcium is a long-known side effect of hydrochlorothiazide. In an observational study on 22 people with high blood pressure taking hydrochlorothiazide long-term (2 – 12 years), 36% developed high blood calcium levels [36, 37, 38].

Severely high blood calcium is more likely with high doses of hydrochlorothiazide, especially in combination with calcium supplements and vitamin D or in those with specific health conditions (hyperparathyroidism and sarcoidosis) [35, 39, 40, 41, 42].

Hydrochlorothiazide is well known to increase blood calcium, which may be beneficial in people with osteoporosis, and may be detrimental if blood calcium increases too dramatically.

4) May Lower Sodium

Low sodium is a dangerous potential side effect of hydrochlorothiazide, especially in older people. Symptoms of severe sodium deficit include [43, 44, 45, 46, 47, 48].

  • Fatigue
  • Muscle weakness and cramps
  • Nausea, vomiting, lack of appetite
  • Headaches
  • Confusion, memory loss, and sleepiness
  • Seizures

The risk increases in combination with:

  • Potassium-sparing diuretics (triamterene, amiloride) [49, 50]
  • Angiotensin II receptor blockers (losartan, olmesartan, telmisartan) [51, 52, 53]
  • Anti-seizure medication (carbamazepine) [54]
  • Antidepressants (paroxetine, sertraline) [55]
Hydrochlorothiazide decreases sodium, and it may do so to a dangerous extent. The potential danger of this effect increases when hydrochlorothiazide is combined with other blood pressure-reducing drugs.

5) May Lower Magnesium

Long-term hydrochlorothiazide therapy reduces the production of a protein responsible for magnesium uptake in the kidneys (Trpm6). This may lead to magnesium deficiency, which in severe cases can cause [56, 57]:

  • Muscle cramps, tremors, and seizures
  • Irregular heartbeat
  • Low blood levels of calcium, potassium, and the parathyroid hormone
  • Apathy
  • Delirium, and even coma

In an observational study on almost 250 people on hydrochlorothiazide (50 mg/day), almost 20% developed low magnesium levels. Magnesium supplements (such as a potassium-magnesium-citrate formula) could correct the deficiency in most cases [58].

About a fifth of people taking hydrochlorothiazide may develop low magnesium, which can usually be reversed by taking magnesium supplements.

6) May Increase Blood Sugar Levels

Taking thiazide diuretics was associated with high blood sugar levels in reviews of 16k people with high blood pressure. Lower doses are recommended to avoid it [59, 60, 61, 62, 63].

Hydrochlorothiazide use was linked to an increased risk of diabetes, especially in obese people, in an observational study on almost 400 people [64].

The combination with amiloride or losartan reduced this risk of this side effect in 2 trials on over 300 people [18, 65].

7) May Increase Blood Fats

Diuretics may raise blood levels of total cholesterol, LDL-cholesterol, and triglycerides, increasing the risk of heart disease and stroke. Hydrochlorothiazide specifically can increase triglycerides and cholesterol levels, as seen in 2 clinical trials on over 700 people [66, 67, 68, 69].

8) May Increase Skin Sensitivity to Light

In rare cases, hydrochlorothiazide therapy followed by sun exposure may cause skin conditions such as:

  • Rash [70, 71, 72]
  • Redness and sunburn-like eruptions [71, 73, 74]
  • Blistering and swelling [75, 76]
  • Skin lupus [77, 78, 79, 80]
  • Decreased skin pigmentation [81]
  • Skin fragility [82]
  • Lip inflammation [83]

More recently, long-term hydrochlorothiazide use was associated with an increased risk of 5 different skin cancer types in studies on over 100,000 people [84, 85, 86].

In a study in mice, hydrochlorothiazide increased the rate of mutations after exposure to UV light, which may explain the increased incidence of skin cancer in people taking this drug [87].

People taking hydrochlorothiazide may have increased sensitivity to light and increased susceptibility to skin cancer and UV damage.

9) May Cause Vision Problems

Electrolyte and water imbalances caused by hydrochlorothiazide may lead to fluid buildup in the eyes, which can cause vision problems, nearsightedness, and glaucoma [88, 89, 90, 91, 92].

10) Other Adverse Effects

Other reported adverse effects of hydrochlorothiazide therapy include:

  • Fluid buildup in the lungs [93, 94, 95]
  • Allergic reactions [96, 97, 98]
  • Fever [99, 100]
  • Acute respiratory distress syndrome (ARDS) [101]
  • Diabetes insipidus [102]
  • Heart inflammation [103]
  • Hearing disorders [104]
  • Impotence [105]

Special Considerations

Hydrochlorothiazide increases the frequency of urination. To avoid having to get up at night to go to the toilet, it’s better not to take it in the evening.

According to the FDA, the risk of hydrochlorothiazide use during pregnancy cannot be ruled out (category C). Thus, it is recommended in pregnancy only if its potential benefits outweigh the risks [106].

Small amounts of hydrochlorothiazide can pass into breast milk. Breastfeeding women should consult their doctors before taking hydrochlorothiazide [107].

Because elderly people may break down and excrete hydrochlorothiazide slower, they may need a lower dose or a different dosing schedule [108].

Hydrochlorothiazide is excreted through the kidneys. People with kidney failure should take hydrochlorothiazide with caution, since the drug may build up in their body and cause adverse effects [109].

Hydrochlorothiazide may worsen the following conditions and should be taken with caution by people who suffer them:

  • Poor liver function [110]
  • Lupus [111]
  • High cholesterol [68]
  • High blood sugar [112]
  • Gout [30]

Importantly, hydrochlorothiazide should be avoided by people with the following conditions:

  • Extremely reduced urine production (anuria) [113]
  • Allergy to sulfonamides [98]
Hydrochlorothiazide has not been demonstrated to be completely safe in pregnancy and is only prescribed to pregnant women when there is no other option. Breastfeeding mothers, elderly people, and people with kidney failure and some other conditions should not take hydrochlorothiazide.

Drug Interactions

To help avoid interactions, your doctor should manage all of your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs you’re taking. Talk to your healthcare provider to find out how hydrochlorothiazide might interact with something else you are taking.

Hydrochlorothiazide may enhance the blood pressure-lowering effect of drugs such as:

  • Renin-angiotensin system blockers (zofenopril, losartan, atenolol, aliskiren) [114, 115, 116]
  • Calcium channel blockers (amlodipine) [117]
  • Anti-anxiety drugs (phenobarbital) [118]
  • Sedatives (morphine, codeine) [119]
  • Alcohol [120]

This can be desirable in some cases (e.g., fixed-dose combinations with renin-angiotensin system blockers) but may cause blood pressure to drop too much in others.

The effects of hydrochlorothiazide on water, electrolyte, and uric acid excretion may be enhanced in combination with drugs such as:

  • Carbonic anhydrase blockers (acetazolamide) [22]
  • Loop diuretics (furosemide) [121]
  • Potassium-sparing diuretics (triamterene, amiloride, spironolactone) [122, 19]
  • Vasopressin blockers (tolvaptan) [123]
  • Anti-gout medication (probenecid) [124]

Hydrochlorothiazide increases lithium uptake in the kidneys, which raises its concentration in the blood and slows its elimination. Indeed, several cases of lithium intoxication due to hydrochlorothiazide use have been reported [125, 126].

Because hydrochlorothiazide increases blood sugar levels, it may decrease the effect of antidiabetic drugs (such as gliquidone and metformin) [127].

The cholesterol-lowering drugs cholestyramine and colestipol reduce hydrochlorothiazide uptake, which may decrease its effects [128, 129].

Anti-inflammatory glucocorticoids such as prednisone have a strong diuretic effect. Their combination with hydrochlorothiazide may cause an excessive loss of electrolytes, especially potassium [130, 131].

The blood pressure-lowering effect of hydrochlorothiazide may be reduced in people taking NSAID anti-inflammatory drugs such as naproxen or ibuprofen [132].

Hydrochlorothiazide has multiple potentially dangerous interactions with other drugs. To avoid unexpected interactions, carefully discuss all of your medication with your doctor before taking this diuretic.

Potential Natural Alternatives to Hydrochlorothiazide

These are some substances and herbs that have some of the same mechanisms of action hydrochlorothiazide. You may try the herbal remedies listed below if you and your doctor determine that they could be appropriate. None of them should ever be done in place of what your doctor recommends or prescribes.

Most importantly, these substances haven’t been sufficiently tested. The effects of horsetail, black cumin, dandelion, coffee, and pomegranate have been evaluated in few clinical trials with small numbers of people, while those of tea, garlic, caraway, parsley, raspberry, and oregano have only been tested in animals. Additionally, only roselle and horsetail have been compared to hydrochlorothiazide in humans, each one in one clinical trial [133, 134].

To sum up, while some of these remedies may help in people with mild symptoms of high blood pressure and water retention, none of them can be considered a realistic alternative to hydrochlorothiazide based on the existing evidence.

Insufficient Evidence

1) Roselle

Roselle (Hibiscus sabdariffa) tea is used worldwide for high blood pressure. This species of Hibiscus contains two polyphenols identified as ACE inhibitors and the flavonoid quercetin, which contributes to blood vessel relaxation [135, 136, 137].

Roselle tea 1x – 2x/day for up to 6 weeks lowered blood pressure in 3 clinical trials on almost 200 people with moderately high blood pressure, but only caused a slight effect in another (on 75) [138, 139, 140, 141].

In a clinical trial on 80 people with mildly high blood pressure, roselle tea (150 mg/kg per day) was more effective than hydrochlorothiazide (25 mg/day) at lowering blood pressure and didn’t cause sodium, potassium, and chloride imbalance [133].

In rats and rabbits, the combination of roselle extract (20 – 40 mg/kg) with hydrochlorothiazide (10 mg/kg) increased urine production and reduced sodium, chloride, and bicarbonate excretion. Because it also slowed hydrochlorothiazide elimination, the combination may not be safe [142].

Roselle has also been traditionally used for kidney stones. One clinical trial on 18 men found that roselle tea increased uric acid excretion, while the extract decreased the buildup of stone-forming substances in the kidneys (such as calcium and oxalate) in rat studies [143, 144, 145, 146].

Although promising, the evidence to suggest roselle as an alternative to hydrochlorothiazide is limited. Larger, more robust clinical trials are needed.

2) Horsetail

Horsetail (Equisetum spp.) has long been used as a diuretic and is currently sold as a tea and in capsules for this purpose. In a clinical trial on 25 healthy people, the extract of the Andean horsetail (0.75 g/day for 2 days) had diuretic effects. It slightly increased sodium, potassium, and chloride flushing [147].

In a clinical trial on 36 healthy men, 900 mg/day of field horsetail (Equisetum arvensis) extract had the same diuretic effect as 25 mg hydrochlorothiazide but a much lower risk of potassium and sodium deficits [134].

In a study in rats, the extracts of four different Mexican horsetail species (Equisetum fluviatile, E. hiemale var. affine, E. giganteum, and E. myriochaetum) were as effective as hydrochlorothiazide and had a similar mechanism of action [148].

Similar to the case of roselle, the use of horsetail as a natural diuretic is promising but the evidence to support it is insufficient. Further research is required.

Caution: Horsetail should be avoided by people with HIV, since it reduced the effect of antiviral drug combinations (lamivudine/ zidovudine/efavirenz and emtricitabine/tenofovir) in two cases [149].

3) Black Cumin

Black cumin (Nigella sativa) has been traditionally used for cooking and to improve a wide range of diseases, including high blood pressure [150].

In a clinical trial on 76 elderly people with high blood pressure, black cumin seed extract (300 mg 2x/day) only caused a very mild reduction in blood pressure [151].

In studies in rats, black cumin extract (50 – 100 mg/kg) acted as a diuretic, increasing urine production, sodium and potassium excretion [152, 153].

In a study in rats, black cumin oil (5 ml/kg for 28 days) reduced blood and urine levels of calcium, phosphate, and oxalate. It increased urine production and reduced the risk of developing kidney stones. Both black cumin extract and its main active compound (thymoquinone) reduced calcium oxalate buildup in rat kidneys [154, 155, 156].

A single clinical trial and a few animal studies cannot be considered sufficient evidence that black cumin is an effective diuretic. More research is needed.

4) Dandelion

Dandelion (Taraxacum officinale) and related plants have been cherished for their diuretic benefits in both traditional Chinese and Ayurvedic medicine for over 2,000 years. Its potassium-rich leaves may account for its diuretic activity [157, 158].

A commercial dandelion leaf extract (8 mL 3x/day) increased urination in a clinical trial on 17 people [157].

In rats, dandelion leaf extract (8 mL/kg) had a diuretic effect comparable to a strong diuretic drug (furosemide 80 mg/kg) and prevented kidney stones [159, 160].

Although employed in traditional medicine for millennia, note that the scientific evidence supporting its use is limited to a small clinical trial and a couple of animal studies. Therefore, we cannot conclude that dandelion is an effective diuretic.

5) Coffee

Caffeine is a natural diuretic that competes with adenosine for binding to its receptors. This blocks sodium uptake in the kidneys and increases water and sodium elimination [161, 162].

Moderate doses of caffeine (at least 300 mg) increase urination in people who don’t drink coffee regularly. In contrast, a moderate coffee intake (4 mg/kg caffeine 4x/day) had no effect on water balance in a clinical trial on 52 men used to the effects of caffeine [163, 164].

Some people are sensitive to caffeine, while coffee can also worsen inflammation. For these reasons, we don’t generally recommend coffee as a diuretic for most people.

To sum up, coffee has been investigated as a diuretic in a few clinical trials with mixed results. Thus, the evidence to support its use is insufficient.

6) Pomegranate

Pomegranate is very rich in antioxidants, which protect the urinary tract from infections and kidney stones [143].

In a clinical trial on 30 people, pomegranate extract reduced calcium oxalate buildup in urine, which might prevent kidney stones. In rats, pomegranate extract reduced kidney damage and the buildup of calcium, oxalate, and phosphate in the urine [165, 166].

Pomegranate has only been investigated for a non-approved use of hydrochlorothiazide (kidney stones), since the evidence to support it is insufficient.

Animal Research (Lack of Evidence)

Scientists are also investigating the effectiveness of other natural substances traditionally used as diuretics or for kidney stones. Because the research is still at the animal and cell stage, there is no evidence to support their purported benefits.

7) Black and Green Tea

As is the case for coffee, black and green tea are natural diuretics due to their caffeine content [163].

Both black (300 – 2,400 mg/kg) and green tea (100 – 500 mg/kg) had diuretic effects in two studies in rats. The combination of green tea with hydrochlorothiazide (10 mg/kg) increased the effects and reduced potassium loss [167, 168].

In rat studies, green tea extract added to hydrochlorothiazide prevented heart damage due to its antioxidant effects [169, 170, 171].

8) Garlic

Garlic is a common food ingredient that has been used in traditional medicine for over 2,000 years. Its benefits for the heart and blood vessels are well-known [172].

Garlic extract acted as a diuretic in animals, increasing urine production. In dogs, it also reduced blood pressure, slowed heart rate, and increased sodium and chloride flushing [173, 174, 175, 176, 177].

9) Caraway

Caraway (Carum carvi) is a spice that has long been traditionally used for high blood pressure, water retention, and digestive disorders in countries such as Morocco and India [178].

In rats, caraway extract (100 mg/kg) was as effective as the diuretic furosemide (10 mg/kg) at increasing urine production. The extract also enhanced sodium and potassium flushing [179].

10) Parsley

Parsley (Petroselinum sativum) has been used as a diuretic in folk medicine for centuries. Although no studies have been done in humans, parsley extract increased urine production in 2 studies in rats [180, 173].

11) Raspberry

Raspberry is a popular fruit with the capacity to release kidney stones from the urinary tract. In animal studies, raspberry extract increased urine production, reduced the oxalate, calcium, and phosphorus buildup in the urine. Overall, it helped prevent kidney stones [143, 181, 182].

12) Oregano

Oregano is a spice that has traditionally been used for water retention and kidney stones. In rats, oregano extract prevented kidney stone formation. It also reduced stone-forming calcium oxalate crystals in test tubes [183].

Takeaway

Hydrochlorothiazide is a diuretic mostly used to treat high blood pressure and water retention. Side effects such as mineral (sodium, potassium, or magnesium) deficiency, high blood calcium, high blood uric acid, increases in blood fats and sugars, skin sensitivity to light, and even vision problems are not uncommon.

Many natural alternatives to hydrochlorothiazide exist. Natural remedies will most benefit people with mildly increased blood pressure or slight water retention. Herbs such as Roselle, horsetail, and black cumin are safe diuretics that support general wellness. However, they should never be used in place of something your doctor recommends or prescribes.

Further Reading

About the Author

Carlos Tello

Carlos Tello

PhD (Molecular Biology)
Carlos received his PhD and MS from the Universidad de Sevilla.
Carlos spent 9 years in the laboratory investigating mineral transport in plants. He then started working as a freelancer, mainly in science writing, editing, and consulting. Carlos is passionate about learning the mechanisms behind biological processes and communicating science to both academic and non-academic audiences. He strongly believes that scientific literacy is crucial to maintain a healthy lifestyle and avoid falling for scams.

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