How can I lower my alkaline phosphatase?

How to Lower Alkaline Phosphatase

The approach to lowering alkaline phosphatase depends entirely on identifying and treating the underlying cause—there is no direct "ALP-lowering" therapy independent of addressing the source disease. Your strategy must first determine whether the elevation originates from liver, bone, or other sources, then target that specific pathology.

Initial Diagnostic Step: Confirm the Source

Measure gamma-glutamyl transferase (GGT) concurrently with ALP to confirm whether the elevation is hepatobiliary in origin. 1 If GGT is elevated, the source is likely liver or biliary tract; if GGT is normal, consider bone disease, intestinal sources, or physiologic causes. 1 When GGT is unavailable, obtain ALP isoenzyme fractionation to quantify the percentage derived from liver versus bone. 1

Hepatobiliary Causes: Treatment Strategies

Cholestatic Liver Diseases

For primary biliary cholangitis (PBC), initiate ursodeoxycholic acid (UDCA) at 13-15 mg/kg/day, which is the only FDA-approved therapy that lowers ALP and improves transplant-free survival. 1 Up to 40% of UDCA-treated patients have persistently elevated ALP, which correlates with reduced survival. 1 For inadequate responders, obeticholic acid can be added as combination therapy or used as monotherapy in UDCA-intolerant patients. 1

In primary sclerosing cholangitis (PSC), falling ALP—defined as normalization or reduction below 1.5× upper limit of normal—stratifies for improved outcome independent of therapeutic modality. 2, 3 Abrupt ALP elevations in PSC often reflect transient obstruction from inflammation, bacterial cholangitis, sludge, or choledocholithiasis rather than disease progression, and warrant evaluation for dominant stricture with MRCP or ERCP. 2, 1

Biliary Obstruction

If imaging reveals common bile duct stones, proceed directly to ERCP for stone extraction within 24-72 hours to prevent ascending cholangitis and resolve obstruction. 1 After successful stone removal, ALP typically normalizes within weeks to months. 1

Drug-Induced Cholestasis

Discontinue the offending medication immediately, particularly in patients ≥60 years where cholestatic drug-induced liver injury comprises up to 61% of cases. 1 Cholestatic patterns resolve more slowly than hepatocellular injury, typically returning to baseline within 6 months after removing the causative agent. 1

Bone-Related Causes: Treatment Strategies

High Bone Turnover in Postmenopausal Women

Bisphosphonate therapy (alendronate or risedronate) effectively lowers ALP in postmenopausal women with elevated levels due to high bone turnover. 4 In a study of 626 postmenopausal osteoporotic women, bisphosphonate treatment decreased elevated ALP to normal range, with the ALP reduction strongly correlating with decreased bone-specific alkaline phosphatase (BAP). 4 The FDA-approved dosing for alendronate is 70 mg once weekly or 10 mg once daily for osteoporosis treatment. 5

Paget's Disease of Bone

For Paget's disease, alendronate 40 mg once daily for 6 months is the FDA-approved regimen. 5 Re-treatment may be considered in patients who relapse (based on increases in serum ALP measured periodically) or who fail to normalize their serum ALP. 5

Secondary Hyperparathyroidism and Renal Osteodystrophy

Active vitamin D therapy (alphacalcidol or calcitriol) significantly reduces ALP in both primary and secondary hyperparathyroidism by decreasing bone turnover. 6 In chronic kidney disease patients with secondary hyperparathyroidism, intravenous alphacalcidol reduced serum ALP from 3.5 ± 3.1 to 2.6 ± 1.7 μkat/L over 4 months. 6 The combination of elevated PTH and elevated ALP strongly indicates high-turnover bone disease requiring treatment. 1

X-Linked Hypophosphatemia: Specialized Management

In children with X-linked hypophosphatemia (XLH), conventional treatment with oral phosphate supplements (20-60 mg/kg/day elemental phosphorus divided into 4-6 doses) plus active vitamin D (calcitriol 20-30 ng/kg/day or alfacalcidol 30-50 ng/kg/day) progressively lowers ALP as rickets heals. 2 The dose should be adjusted based on improvement in ALP levels, with higher frequencies (4-6 times daily) recommended in young patients with high ALP until normalization occurs. 2

Burosumab (anti-FGF23 antibody) is superior to conventional therapy for normalizing ALP in XLH patients, with treatment continued beyond growth completion to optimize bone mass accrual. 2 Serum ALP serves as a reliable biomarker of rickets activity and treatment response. 1

Monitoring and Follow-Up

Repeat ALP measurement in 7-10 days to confirm reproducibility and direction of change when the etiology is unclear. 1 For cholestatic patterns, expect slower normalization than hepatocellular injury—typically 6 months after removing the causative factor. 1 In PSC, ALP reduction below 1.5× ULN within 12 months independently predicts improved transplant-free survival. 3

Critical Pitfalls to Avoid

• Do not attempt to "lower ALP" without first identifying the source—treating the wrong organ system wastes time and may cause harm. 1
• Do not assume mild ALP elevation in postmenopausal women is benign—it often reflects high bone turnover amenable to bisphosphonate therapy. 4
• Do not delay ERCP when imaging shows bile duct stones—conservative management carries a 25.3% risk of unfavorable outcomes versus 12.7% with active extraction. 1
• Do not overlook sepsis as a cause of extremely high ALP (>1,000 U/L)—it can occur with normal bilirubin and requires urgent treatment of the underlying infection. 7, 8