Mild hypophosphatemia: Does it really cause muscle weakness?

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I recently saw a patient with proximal muscle weakness and mild hypophosphatemia, and I wondered whether a serum phosphorous level of 2.2 mg/dL could be the cause. We know that moderate hypophosphatemia is associated with skeletal and smooth muscle dysfunction. Acute hypophosphatemia can lead to rhabdomyolysis, especially in those with chronic phosphate depletion (eg Alcoholics). Severe hypophosphatemia is associated with metabolic encephalopathy and symptoms of irritability, paresthesias, and even coma.

A pubmed search specifically looking for muscle effects of mild hypophosphatemia returned one paper. It examined respiratory muscle function in an inpatient population. The small study evaluated 23 hospitalized patients with serum phosphate levels less than 2.5mg/dl and compared them to a control group of 11 normophosphatemic inpatients. Mean age, length of stay, and number of predisposing factors for hypophosphatemia in each group was not statistically different. Mean initial serum phosphate level for the hypophosphatemic group was 1.9 +/- 0.4mg/dl compared to 3.6 +/- 0.5 mg/dl for the normophosphatemic group, with a correlating statistical difference in the measures of respiratory muscle strength. After about 2 days of repletion, the mean serum phosphate level increased in the hypophosphatemic group to 3.5 +/- 0.8 mg/dl with no difference in the respiratory muscle strength measurements after repletion in the two groups.

  • 43 % (3/7) of those with phosphate levels 2.1-2.5mg/dl demonstrated muscle weakness,
  • 75% (9/12) of those with phosphate levels 1.5-2.0mg/dl demonstrated muscle weakness, and all (4) of those with phosphate levels less than1.5mg/dl demonstrated muscle weakness.

Based on my brief literature search, it appears that even mild hypophosphatemia is associated with skeletal muscle weakness, and that this weakness is quickly reversible with repletion to normal levels.

Mary Lieu M.D.

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