Hydrochlorothiazide is among the most frequently prescribed drugs worldwide, approved for high blood pressure and water retention. Unfortunately, this diuretic may disturb electrolytes, uric acid, sugars, and fats in the blood. Some herbal remedies may be a safer option for people with mild symptoms. Read on to learn more, along with a breakdown of the best natural alternatives.

Note: 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 literature, along with 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 with urine by blocking sodium uptake in the kidneys [R, R, R+].

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 [R+].

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

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

Additional uses, not approved by the FDA, include the following [R]:

  • 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 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 [R+].

Mechanism of Action

Hydrochlorothiazide and other thiazide diuretics block a kidney cell protein (SLC12A3) that absorbs sodium and chloride from the urine. By doing so, they increase the flushing of sodium, chloride, and water, while reducing their reuptake into the blood [R].

Hydrochlorothiazide starts to act within 2h, peaks after 4 h, and last for 6 – 24 h [R+].

At first (over 2 – 12 weeks), hydrochlorothiazide lowers blood pressure by reducing blood volume. As less blood is pumped by the heart, blood vessels relax. The drug continues to lower blood pressure long-term, probably by keeping the blood vessels widened [R+, R+].

On the downside, low blood volume activates a compensatory pathway in the body (called the renin-angiotensin system). This pathway flushes more potassium and builds up uric acid, which triggers the main adverse effects: low potassium and gout [R+, R+].

Uses of Hydrochlorothiazide

1) Hydrochlorothiazide Lowers Blood Pressure

Hydrochlorothiazide Alone

The use of hydrochlorothiazide for reducing blood pressure has been well established since the 1950s. According to data from 33 clinical trials and almost 14k people, this diuretic (6.25 – 50 mg/day) effectively reduces blood pressure, higher doses having a stronger effect [R+, R].

However, other diuretics (called thiazide-like) may be more effective and safer than hydrochlorothiazide. One such diuretic (chlorthalidone 6.25 – 25 mg/day) reduced high blood pressure to a greater and longer-lasting extent in over 100 studies. 2 clinical trials confirmed this by directly comparing the two drugs on 78 people [R, R, R, R].

The diuretic indapamide in low doses (1.5 – 2.5 mg/day) was as effective and safe as hydrochlorothiazide in over 300 people, having an even stronger effect in some populations (black, Indian, elderly, those with kidney failure or only high systolic pressure) [R, R, R, R, R, R, R].

Bendroflumethiazide is another diuretic that works just as well but at lower doses (2.5 – 5 mg) (81 people) [R, R].

Hydrochlorothiazide in Combination with Other Drugs

Therapy with a single diuretic effectively lowers blood pressure in only 50% of people. The combination of hydrochlorothiazide with at least one more drug additionally lowers blood pressure and allows for lower dosing [R+].

To justify the use of multiple blood-pressure-lowering drugs, it’s important to understand how the body controls blood pressure. The key pathway involved is called the renin-angiotensin system, which raises blood pressure.

The kidneys produce an enzyme called renin, which makes angiotensin I in the blood (from angiotensinogen). Next, the crucial angiotensin-converting enzyme (ACE) makes the potentially harmful angiotensin II (from angiotensin I). Angiotensin II narrows blood vessels, increases salt production, and raises the water-retaining hormone aldosterone [R, R].

In combination with drugs that block this pathway, hydrochlorothiazide will have a stronger blood-pressure-lowering effect. The following drugs are often added to hydrochlorothiazide:

  • ACE inhibitors block the key enzyme that makes angiotensin II (ACE) [R+]. These combinations are quite common. They mostly reduce blood pressure more effectively than either drug alone (with enalapril, captopril, quinapril, fosinopril, benazepril, zofenopril but NOT lisinopril; 12 trials, >3k people) [R, R, R, R, R, R, R, R, R, R, R, R, R].
  • Angiotensin II receptor blockers block the activity of angiotensin II [R+]. Such combinations lowered blood pressure and were well tolerated in 18 clinical trials of almost 15k people (with olmesartan, losartan, telmisartan, valsartan, irbesartan, candesartan) [R, R, R, R, R, R, R, R, R, R, R, R, R, R, R, R, R, R].
  • Beta blockers prevent renin production, aside from blocking the effects of epinephrine [R+]. They helped additionally lower blood pressure in 5 clinical trials on over 1k people (with bisoprolol, nebivolol, metoprolol, atenolol) [R, R, R, R, R].
  • Renin blockers bind to and block renin [R+]. Hydrochlorothiazide was more effective combined with the renin blocker aliskiren in 2 trials on almost 4k people [R, R].

Hydrochlorothiazide is also sometimes combined with other blood-pressure-lowering drugs such as calcium channel blockers (amlodipine) [R+].

Basically, the effect intensifies as more pathways that contribute to high blood pressure are blocked. This may allow for the dosage of each individual drug to be lowered and can potentially reduce side effects. On the downside, side effects are still possible and can be more complex.

Triple Combinations

In people who don’t respond to 2 drugs, a third drug is added. The most common combinations include hydrochlorothiazide, the calcium channel blocker amlodipine, and a sartan (Azilsartan, Valsartan, Olmesartan, Telmisartan – trials on 8k people in total) or Aliskiren [R, R, R, R, R, R, R].

2) Hydrochlorothiazide Reduces Water Retention

Water retention occurs when excess fluids move from the blood vessels into the cavities formed between tissues in the body (interstitium). This happens if the pressure inside the blood vessels becomes higher than in the tissues (especially if the blood protein levels are low). It can be caused by heart failure, kidney disease, or liver cirrhosis [R+].

Heart Failure

In people with heart failure, the heart becomes weaker and pumps less blood. The kidneys attempt to compensate by absorbing more water and salt. Fluids build up and people usually experience high blood pressure along with heart failure [R+].

Small studies back in the late 1950s showed that hydrochlorothiazide (50 – 100 mg 2x/day) can reduce water retention in heart failure (35 people) [R+, R, R+].

Hydrochlorothiazide had a slightly stronger effect than another similar diuretic (quinethazone) in a trial on 7 people. In turn, different diuretics (ticrynafen, furosemide, and indapamide) were as effective as hydrochlorothiazide but had fewer adverse effects in 3 trials on over 100 people [R+, R, R, R].

Hydrochlorothiazide enhanced the effect of the loop diuretic furosemide in a trial on 20 people with heart failure, but the combination increased the risk of low potassium. This can be avoided by combining hydrochlorothiazide with potassium-sparing diuretics (in 5 trials on over 100 people) [R, R+, R, R, R+, R+].

Kidney Failure

In people with kidney failure, high blood sodium levels cause water retention. Hydrochlorothiazide can be used to reduce sodium and water retention [R].

In 2 old studies on 3 people, hydrochlorothiazide combined with the potassium-sparing diuretic spironolactone or the corticosteroid prednisone improved swelling, increased sodium elimination, and reduced potassium excretion [R, R+].

Liver Cirrhosis

Liver cirrhosis can cause water retention in the belly (ascites), due to sodium buildup, impaired blood flow, and kidney dysfunction [R+].

Hydrochlorothiazide (alone or in combination with the corticosteroid prednisone) improved water retention caused by liver cirrhosis in 4 old clinical trials on 21 people [R+, R+, R+, R+].

Other Causes

Water retention is common during pregnancy. In an old clinical trial on almost 100 pregnant women, hydrochlorothiazide and other thiazides improved water retention and decreased blood sodium and potassium levels without damaging the unborn babies [R+].

The antidiabetic drug rosiglitazone can cause water retention. In a clinical trial on 260 people with water retention from this drug, both hydrochlorothiazide and the potassium-sparing diuretic spironolactone helped [R].

3) Hydrochlorothiazide May Improve Diabetes Insipidus

Diabetes insipidus is a rare condition characterized by increased thirst and large amounts of diluted urine. It is caused by low levels of the antidiuretic hormone vasopressin, due to not enough of it being produced, its breakdown (as in pregnancy by the placenta), from drinking too much water, or from kidney defects [R+].

Desmopressin is an analog of vasopressin and the drug of choice. Hydrochlorothiazide is an alternative (it improved this condition in 13 children and 2 adults) [R, R, R].

Hereditary nephrogenic diabetes insipidus is diagnosed during early childhood and usually resolved with thiazide diuretics. Hydrochlorothiazide is normally combined with other drugs (amiloride, indomethacin, rofecoxib, or desmopressin) [R, R, R, R+, R, R+, R, R, R].

Non-hereditary nephrogenic diabetes insipidus is caused by drugs or surgical procedures that damage the kidneys. Hydrochlorothiazide resolved symptoms in 4 adults [R+, R+, R, R].

4) Hydrochlorothiazide May Improve Calcium Balance

Hydrochlorothiazide and other thiazides stimulate calcium uptake into the blood by the kidneys, causing less calcium to be flushed and preventing or improving calcium deficiency [R].

Kidney Stones

Kidney stones are an increasing problem worldwide. 80 – 90% of kidney stones are made of calcium salts. Disorders that increase calcium flushing with the urine were the main cause of kidney stones in a study on over 200 people [R, R+, R].

Hydrochlorothiazide reduced kidney stone formation in trials on over 1k adults and almost 200 children (alone, combined with amiloride, or a drug for osteoporosis called alendronate) [R, R, R, R, R, R, R, R, R, R, R, R].

However, the thiazide diuretics indapamide and chlorthalidone were more effective than hydrochlorothiazide and could be used at lower doses (2 studies on over 100 people with kidney stones) [R, R].

Osteoporosis

Thiazide diuretics may prevent calcium deficiency in osteoporosis. In 4 studies on over 24k people, thiazide use was linked with a reduced risk of bone fractures and mineral loss [R, R, R, R, R].

Hydrochlorothiazide (12.5 – 50 mg/day) preserved bone mineral density in clinical trials on over 1k people (alone or in combination with drugs for high blood pressure or for bone loss) [R, R, R, R, R, R].

Hydrochlorothiazide also prevented bone loss in rats and mice with osteoporosis [R, R, R].

Hypoparathyroidism

Hypoparathyroidism is caused by a lack of the hormone that releases calcium from the bones into the blood (parathyroid hormone). It leads to low calcium and high phosphate blood levels, which can be triggered by damage or removal of the parathyroid gland, genetic or autoimmune causes [R].

In an observational study on 97 people with hypoparathyroidism, 26 required hydrochlorothiazide in addition to calcium and vitamin D to restore calcium balance [R].

Only one case describes hydrochlorothiazide use for hypoparathyroidism in a pregnant woman. It helped improve calcium levels without damaging the baby [R+].

Vitamin D Intake

Vitamin D is used to improve calcium-phosphate disorders caused by hormonal and kidney disorders. However, its long-term use can cause excessive calcium flushing. In an observational study on 19 children and teenagers taking vitamin D, hydrochlorothiazide restored normal urine calcium levels [R, R].

Dent’s Disease

Dent’s disease is a rare inherited kidney defect characterized by high protein and calcium in the urine, calcium buildup in the kidneys, and kidney damage [R+].

Hydrochlorothiazide reduced excessive calcium flushing in 12 children with Dent’s disease but didn’t in 3 (possibly due to the different mutations causing the condition) [R, R+, R+, R+, R, R, R].

6) Hydrochlorothiazide May Improve Ménière’s Disease

Ménière’s disease is a disorder of the inner ear that causes vertigo, temporary hearing loss, ringing in the ears (tinnitus), and stuffy ears. It’s caused by the buildup of fluid in the inner ear [R+].

In 4 studies on almost 200 people with this disease, hydrochlorothiazide reduced vertigo and hearing loss. It was much more effective in people with fluctuating symptoms than in more severe cases. In one study, it only reduced hearing loss (54 people) [R+, R+, R, R, R+].

In a clinical trial on 33 people, a combination of hydrochlorothiazide and another diuretic (triamterene) improved only vertigo. According to a survey of 186 doctors, 72.8% still used this combination to manage Ménière’s disease [R, R].

7) Hydrochlorothiazide May Improve Renal Tubular Acidosis

Renal tubular acidosis (RTA) is an acid-base disorder in which acid accumulates in the body because the kidneys fail to flush it. RTA can be hereditary or caused by autoimmune diseases (lupus, rheumatoid arthritis), toxins, and chronic kidney disease [R].

Hydrochlorothiazide (10 – 38 mg/day) restored normal acid excretion into the urine in 4 children with RTA caused by genetic mutations [R, R, R, R].

Hydrochlorothiazide Side Effects

1) Hydrochlorothiazide 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 [R, R+]:

  • 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 36k people with high blood pressure [R, R, R, R].

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) [R, R, R].

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

  • Triamterene [R, R, R]
  • Amiloride [R, R]
  • Spironolactone [R]

2) Hydrochlorothiazide May Increase Blood Uric Acid

Hydrochlorothiazide can raise blood uric acid levels, which is linked to an increased risk of [R+, R+, R]:

  • Gout [R]
  • High blood pressure [R]
  • Diabetes and obesity [R, R, R]
  • Heart disease [R+]

Hydrochlorothiazide was associated with an increased risk of gout in studies on over 12k people [R, R, R+].

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

3) Hydrochlorothiazide May Increase Blood Calcium Levels

Very high blood calcium can cause [R]:

  • 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 [R, R+, R].

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) [R, R+, R, R, R].

4) Hydrochlorothiazide May Lower Sodium

Low Sodium is a dangerous potential side effect of hydrochlorothiazide, especially in older people. Symptoms of severe sodium deficit include [R+, R, R, R, R, R].

  • 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) [R+, R]
  • Angiotensin II receptor blockers (losartan, olmesartan, telmisartan) [R, R, R]
  • Anti-seizure medication (carbamazepine) [R+]
  • Antidepressants (paroxetine, sertraline) [R+]

5) Hydrochlorothiazide 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 [R, R]:

  • 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 over 240 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 [R].

6) Hydrochlorothiazide 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 [R, R+, R, [R, R].

Hydrochlorothiazide use was linked with an increased risk of diabetes, especially in obese people (observational study on almost 400 people) [R].

The combination with amiloride or losartan reduced this risk of this side effect (2 trials on over 300 people) [R, R].

7) Hydrochlorothiazide 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 (2 clinical trials on over 700 people) [R+, R, R, R+].

8) Hydrochlorothiazide May Increase Skin Sensitivity to Light

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

  • Rash [R+, R+, R]
  • Redness and sunburn-like eruptions [R+, R, R]
  • Blistering and swelling [R, R+]
  • Skin lupus [R, R, R+, R]
  • Decreased skin pigmentation [R]
  • Skin fragility [R]
  • Lip inflammation [R+]

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

In a study on 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 [R].

9) Hydrochlorothiazide 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  [R+, R, R, R+, R].

10) Other Adverse Effects

Other reported adverse effects of hydrochlorothiazide therapy include:

  • Fluid buildup in the lungs [R, R, R]
  • Allergic reactions [R, R, R]
  • Fever [R+, R+]
  • Acute respiratory distress syndrome (ARDS) [R]
  • Diabetes insipidus [R]
  • Heart inflammation [R]
  • Hearing disorders [R]
  • Impotence [R+]

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 [R+].

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

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

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 [R].

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

  • Poor liver function [R]
  • Lupus [R]
  • High cholesterol [R]
  • High blood sugar [R]
  • Gout [R]

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

  • Extremely reduced urine production (anuria) [R+]
  • Allergy to sulfonamides [R]

Limitations and Caveats

Although hydrochlorothiazide is routinely prescribed for water retention, most clinical trials investigating this effect were done on small samples or date back to the 1950s. Trials with larger numbers of people would be required for more detailed information on its effectiveness and safety.

Because diabetes insipidus, Dent’s disease, and renal tubular acidosis are relatively rare, most information on their improvement with hydrochlorothiazide has been obtained from case studies. This makes it difficult to compare doses, combined therapies, and adverse effects.

Most importantly, the natural alternatives to hydrochlorothiazide 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 [R, R].

Drug Interactions

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

  • Renin-angiotensin system blockers (zofenopril, losartan, atenolol, aliskiren) [R, R+, R]
  • Calcium channel blockers (amlodipine) [R]
  • Anti-anxiety drugs (phenobarbital) [R]
  • Sedatives (morphine, codeine) [R]
  • Alcohol [R]

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) [R]
  • Loop diuretics (furosemide) [R]
  • Potassium-sparing diuretics (triamterene, amiloride, spironolactone) [R, R]
  • Vasopressin blockers (tolvaptan) [R]
  • Anti-gout medication (probenecid) [R]

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 [R, R+].

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

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

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

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

Genetic Predispositions & Pharmacogenetics

Blood Pressure Reduction

The kidney protein SLC12A3 takes up sodium and chloride. Because this protein is the target of hydrochlorothiazide, mutations can alter the drug effects [R].

Genes associated with increased response to hydrochlorothiazide include:

  • NEDD4L (rs1008899 variant A, rs292449 variant C, rs4149601 variant G, rs75982813 variant A, and rs4149601 (rs292449 variant GC in white people) [R]
  • BEST3 (rs61747221) [R]
  • PRKCA (rs16960228 variant A) [R]
  • PRKAG2 (rs2727563 variant C) [R]
  • DCC (rs12604940 variant C) [R]
  • EBF1 (rs11953630 variant G in a closed region) [R]
  • YEATS4 (rs7297610 variant C) [R]
  • ADD1  (G614T mutation) [R]
  • GNB3 (C825T mutation) [R]
  • SH2B3 (rs3184504 variant C, but only in white people) [R]
  • TGFBR2 (rs749794 variant T in men and women and rs1155705 variant A and rs11709624 variant C in men only) [R]

In turn, the following genes are associated with high blood pressure despite hydrochlorothiazide therapy (reduced response):

  • SH2B3 (rs3184504 variant C, but only in African Americans) [R]
  • FGF5 (rs1458038 variant T in a closed region) [R]
  • NOS3 (D298N mutation) [R]
  • TGFBR2 (rs3773661 variants G and C and rs7256241 variants TT and GG in women and rs1036096 variant T in men) [R]
  • SLC22A8 (rs10792367 variant C in a closed region) [R]
  • TXNDC11 and SNN (rs3784921 variant G in a region between them) [R]

A mutation in ALDH1A2 (rs261316 variant T) was associated with reduced response to combined therapy of hydrochlorothiazide and atenolol [R].

Bone Mineral Density

In a study on over 100 people, women with DD polymorphisms in the angiotensin-converting enzyme gene (ACE) experienced enhanced bone mineral density from hydrochlorothiazide (those with the II + ID mutation didn’t) [R].

Blood Sugar Levels

Mutated variants of HMGCS2 (rs9943291 variant G), SLC2A2 (rs11920090 variant A), KCNJ1 (rs12795437 variant C and rs11600347 variant A), and TCF7L2 (rs4506565 variant T, rs7903146, rs7901695 variant T, and rs12243326 variant C) were associated with a greater risk of high blood sugar and diabetes from hydrochlorothiazide therapy [R, R, R, R].

Potassium Loss

WNK1 is a protein that activates several sodium and chloride uptake proteins, including SLC12A3. Mutations in WNK1 (rs4980973 variants AA and AG) have been associated with increased potassium loss in response to hydrochlorothiazide therapy. Additionally, mutations in this protein that alter SLC12A3 activation may increase or reduce the effect of hydrochlorothiazide on blood pressure [R, R].

Blood Uric Acid

Mutated variants of LUC7L2 (rs6947309 variant T), ANKRD17 (rs16849146 variant C), FTO (rs4784333 variant C), PADI4 (rs2477134 variant G), and PARD3B (rs236829 variant T) in African Americans and GRIN3A (rs1418243 variant A) in white people have been associated with increased uric acid buildup in the blood in response to hydrochlorothiazide [R].

Drug Forms

Hydrochlorothiazide comes as oral tablets and capsules. The available strengths are 12.5, 25, and 50 mg.

Hydrochlorothiazide is available as a generic drug or sold under commercial brand names such as:

  • Hydrodiuril
  • Microzide
  • Zide
  • Esidrix
  • Oretic
  • Aquazide H
  • Hydrocot

Dosage

The following doses are typical:

  • High blood pressure: 12.5 – 50 mg/day (alone) or 6.25 – 25 mg/day (in double and triple combinations) in adults and teenagers [R, R+, R, R]
  • Water retention: typically 25 – 100 mg/day in adults, but up to 300 mg/day have been used in clinical trials [R+, R, R, R+, R+]
  • Diabetes insipidus: 50 mg 2x/day in adults and 1 – 3 mg/kg per day in children [R+, R, R+]
  • Kidney stone prevention: 25 – 50 mg 2x/day in adults and 1 mg/kg per day in children [R, R, R]
  • Osteoporosis: 12.5 – 50 mg/day in adults [R, R]
  • Hypoparathyroidism: 12.5 – 25 mg/day in adults [R+]
  • Calcium deficiency due to vitamin D therapy: 1-2 mg/kg in children [R]
  • Dent’s disease: 0.2 – 2 mg/kg per day in children [R+, R]
  • Ménière’s disease: 25 mg 2x – 3x/day in adults [R+, R]
  • Renal tubular acidosis: 10 – 38 mg/day in children [R, R+]

User Experiences

The vast majority of users took hydrochlorothiazide for reducing high blood pressure. About half of them were satisfied with the drug since it lowered their blood pressure and helped with weight loss (due to its diuretic action) without serious side effects.

However, a lot of users experienced many adverse effects. The most commonly reported side effects were dizziness, weakness, muscle pain and cramps, increased heart rate, dehydration, and headache. Other, less frequent adverse effects included skin rashes, gout, impotence, constipation, depression, and blurred vision.

People who used hydrochlorothiazide to reduce water retention mostly reported less swelling. In a few cases, the users complained that it didn’t work or even made their swelling worse.

People using hydrochlorothiazide to prevent kidney stones were mostly satisfied and reported a clear reduction in their urine calcium levels and incidence of kidney stones. However, several of them complained about side effects, while one user experienced a worsening.

Potential Natural Alternatives to Hydrochlorothiazide

These are some substances and herbs that have some of the same mechanisms of action tohydrochlorothiazide. However, we do not recommend that you stop your medication unless your doctor thinks it’s a good idea.

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 [R, R, R].

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) [R, R, R, R].

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 [R].

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 [R].

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; rat studies) [R, R, R, R].

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 [R+].

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 [R].

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 [R].

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 [R].

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 [R].

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 [R].

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

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 [R, R, R].

4) Dandelion

Dandelion (Taraxacum officinale) and related plants have are 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 [R, R+].

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

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 [R+, R].

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 [R, R].

Moderate doses of caffeine (at least 300 mg) increase urination in people who don’t drink coffee regularly. In turn, 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 [R, R].

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.

6) Black and Green Tea

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

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 [R, R].

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

7) Pomegranate

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

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 [R, R].

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 [R+].

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 [R+, R, R+, R, R].

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 [R].

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 [R].

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 [R, R+].

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 [R, R, R].

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 [R].

Take-Away:

Hydrochlorothiazide is a diuretic mostly used to treat high blood pressure and water retention. It is often combined with other drugs for a stronger effect, although side effects 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.

About the Author

Carlos Tello, PhD (Molecular Biology)

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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