What medications, such as ammonium chloride, can make urine more acidic?

Medications That Acidify Urine

Ammonium chloride is the most effective medication for urinary acidification, superior to ascorbic acid (vitamin C), which requires impractically high doses (12 g/day or more) to achieve adequate acidification. 1, 2

Primary Urinary Acidifying Agents

Ammonium Chloride

• Most effective pharmaceutical option for lowering urinary pH 2, 3
• Achieves target pH <6.0, with optimal effect at pH <5.5 1, 2
• Used clinically when methenamine salts require acidic urine for antibacterial activity (formaldehyde generation depends on low pH) 1
• Produces metabolic acidosis through direct acid loading 4
• Clinical caveat: Stimulates renin-angiotensin-aldosterone system and increases urinary sodium, potassium, and chloride losses 4

Methionine (D,L-Methionine)

• Second most effective acidifying agent 3
• Produces similar urinary acidification to ammonium chloride in some studies 5
• May have less impact on calcium excretion compared to ammonium chloride, though evidence is mixed 5
• Effectiveness depends on dietary cation-anion difference 5

Ascorbic Acid (Vitamin C)

• Significantly less effective than ammonium chloride 1, 2
• Doses up to 4 g/day show no significant effect on mean urinary pH 1, 2
• Requires doses of 12 g/day or more, administered every 4 hours, to adequately acidify urine 1, 2
• May increase urinary formaldehyde concentrations with only slight pH changes when used with methenamine 1
• Not practical for routine clinical use due to dosing requirements 1

Clinical Applications Requiring Urinary Acidification

Methenamine Salt Therapy

• Requires maintaining urinary pH below 6.0 for effectiveness 1, 2
• Optimal bactericidal effect achieved at pH <5.5 1, 2
• Formaldehyde (active antibacterial metabolite) generation is pH-dependent 1
• Important limitation: Methenamine salts are NOT recommended routinely for long-term catheterization 1, 2
• May be considered for short-term catheterization (<1 week) after gynecologic surgery 1

Urinary Stone Management Context

• Contraindication: Acidic urine (pH ≤5.5) increases uric acid stone formation risk 2
• Uric acid solubility is only 15 mg/dL at pH 5.0, increasing to 200 mg/dL at pH 7.0 1, 2
• Do not acidify urine in uric acid stone formers—opposite approach needed (alkalinization to pH 6.0) 2

Practical Considerations

Monitoring Requirements

• Verify urinary pH to confirm adequate acidification 1, 2
• Target pH <6.0, optimally <5.5 for methenamine effectiveness 1, 2
• Monitor serum electrolytes when using ammonium chloride due to metabolic acidosis risk 4
• Watch for increased urinary electrolyte losses (sodium, potassium, chloride) 4

Dietary Factors

• High protein diets naturally produce more acidic urine 2, 3
• Dietary cation-anion difference affects effectiveness of acidifying agents 5
• Consider dietary modification as adjunct to pharmaceutical acidification 3

Common Pitfalls

• Avoid sodium bicarbonate or alkalinizing agents when using methenamine salts 1
• Do not use urinary acidification for infection prevention in neurogenic bladder patients 2
• Recognize that xanthine has low solubility even in acidic urine, creating risk of xanthine crystalluria if allopurinol is used concurrently 1