Alkaline phosphatase, or alk phos, is part of a Comprehensive Metabolic Panel (CMP) typically run at least once a year. While most of the time, the test is screening for elevation of alk phos (often due to liver disease or biliary obstruction), I’ve seen low alk phos relatively often. There are several possible reasons for this—some more common and some less.

What Alkaline Phosphatase Does

Alk phos is a group of identical enzymes found in all body tissues, though most of it is in the liver. It is also found in higher concentrations in the bones, intestines, pancreas, and kidneys, as well as in the placenta of pregnant women.

Alk phos breaks phosphates off of proteins. We still don’t know much about why this is necessary, but this study suggests that its role has to do with producing ATP. ATP is the body’s primary energy currency in the body, produced inside the mitochondria.

Like all enzymes, alk phos requires mineral cofactors. These are minerals necessary for the enzyme to do its work. In the case of alk phos, the minerals involved are zinc and magnesium.

Physiologic Causes of Alkaline Phosphatase Elevation

In addition to the pathologic causes, sometimes alk phos elevation can be normal.

Because alk phos is high in bones, where it is involved in bone mineralization, it tends to be elevated in growing children.

In people with blood types B or O, serum alk phos levels (probably from the intestines) also rise for up to 12 hours after eating a fatty meal. This implies a role in macronutrient absorption at least. (This also means that for individuals with blood types B or O, the test should be run fasting.)

Causes of Low Alkaline Phosphatase

Because alk phos requires zinc and magnesium as cofactors, low levels in the serum can most obviously be due to low levels of these minerals. Chronic elevation of a competitive inhibitor of zinc, like copper can have a similar effect. This can occur with conditions like the rare disorder Wilson’s Disease.

Since alk phos breaks down proteins, protein deficiency (due to either malnutrition or malabsorption) can also be a factor. This is the reason for the association of low alk phos levels and celiac disease. But according to this article, intestinal alk phos also plays a role in maintaining the integrity of the gut barrier: i.e. protecting against leaky gut syndrome. So in cases of leaky gut, it stands to reason that alk phos would also be low.

Hypothyroidism can also affect the liver, and alter liver function tests—including alk phos

Levels can also fall with pernicious anemia, and stabilize with administration of Vitamin B12. It also appears that B12 deficiency in general, regardless of the cause, can lower alk phos levels.

The Upshot

If your alk phos levels are chronically low, consider looking at vitamins and minerals (especially B12, magnesium, copper, and zinc), thyroid function, and gut health.

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