What are the causes of low Alkaline Phosphatase (ALP) levels?

From the Guidelines

Low alkaline phosphatase (ALP) levels in the blood may indicate several underlying conditions that require medical attention, and treatment should focus on addressing the underlying cause rather than solely on increasing ALP levels. If you have low ALP, you should consult with your healthcare provider for proper evaluation and diagnosis. Common causes include malnutrition, protein deficiency, zinc deficiency, magnesium deficiency, Wilson's disease, hypothyroidism, and certain rare genetic conditions like hypophosphatasia 1. Your doctor will likely recommend additional blood tests to check for nutritional deficiencies, thyroid function, and other potential causes.

Some key points to consider in the evaluation of low ALP include:

• The importance of assessing for Wilson's disease, particularly in young patients with low ALP and high bilirubin levels 1
• The role of nutritional deficiencies, such as zinc, vitamin D, and magnesium, in contributing to low ALP levels 1
• The need for careful evaluation and management of underlying conditions, such as hypophosphatasia, to prevent long-term complications 1

If nutritional deficiencies are identified, supplementation with zinc (15-30 mg daily), vitamin D (1000-2000 IU daily), or magnesium (300-400 mg daily) may be recommended, but only after confirming deficiencies through testing 1. Low ALP is significant because this enzyme plays important roles in liver function, bone formation, and other metabolic processes throughout the body. Unlike high ALP, which is more commonly discussed, low levels can sometimes indicate serious underlying conditions that require proper medical evaluation rather than self-treatment.

From the Research

Low Alkaline Phosphatase

• Low serum alkaline phosphatase (ALP) is an epiphenomenon of many severe acute injuries and diseases, and can be secondary to drug therapy or acquired disorders such as malnutrition, vitamin and mineral deficiencies, and endocrine disorders 2
• Hypophosphatasia, a genetic disorder caused by pathogenic variants of the ALPL gene, is a common cause of low serum ALP, and can present with symptoms such as skeletal pain, chondrocalcinosis, calcific periarthritis, dental problems, and stress fractures 2, 3
• The diagnostic approach to patients with low serum ALP involves measuring ALP substrates, such as pyrophosphate, pyridoxal phosphate, or phosphoethanolamine, and gene analysis to confirm the diagnosis of hypophosphatasia 2
• Adult forms of hypophosphatasia can be asymptomatic, and further image evaluations and genetic testing may be necessary to confirm the diagnosis 4

Causes of Low Alkaline Phosphatase

• Low serum ALP can be caused by various factors, including:
  • Drug therapy, such as antiresorptives 2
  • Acquired disorders, such as malnutrition, vitamin and mineral deficiencies, and endocrine disorders 2
  • Genetic disorders, such as hypophosphatasia 2, 3
• Secondary causes of reduced ALP, such as liver disease or bone disease, must be ruled out before considering a diagnosis of hypophosphatasia 4

Diagnosis and Management

• The measurement of total ALP activity in serum or plasma is a useful biomarker in clinical practice, and can help identify patients with low serum ALP 5
• Electrophoretic assays and bone ALP immunoassays can be used to investigate the cause of increased or reduced serum ALP activities 5
• A therapeutic role for ALP has emerged, particularly in the treatment of hypophosphatasia, and ongoing and future studies are exploring its role in other therapeutic areas 5