Causes of Low or High Alkaline Phosphatase (and How to Stabilize it)

You’ve just come back from your doctor, and your tests show abnormal levels of alkaline phosphatase.

You’re not sure what that is or how you got it.

Let’s answer the question “What is alkaline phosphatase?” and explain what it does for your body, plus some of the reasons you might have gotten some abnormal numbers.


What is Alkaline Phosphatase?

Alkaline phosphatase is an enzyme stored in the body that removes phosphates from other molecules.

These are essential components in the development of bones and teeth because they play a role in mineralization (1).

There are different forms of the enzyme, not just the component located in bone.

It’s also found in the intestine, where it helps transport phosphates to the tissue lining or counteracts harmful phosphates in the intestine.

The enzyme is found in nearly all body tissues; however, the most common places are the bones, kidney, liver, and placental tissue (2).

You might have heard it called alkaline phosphate, but the correct name is alkaline phosphatase.


What are the Genetic Factors?

Four different gene codes contribute to the creation of the enzyme (3).

In the intestine, ALPI is the distinction for the enzyme.

ALPP is the tag for placental alkaline phosphatase and its associated role in embryo growth and development.

For future eggs and sperm cells, there’s a slightly different version of placental phosphatase, ALPPL2.

This tag distinguishes its role in embryonic activity and from its role in sex cells.

ALPL is the name for alkaline phosphatase in the liver, bone, and kidneys.

It is also called Tissue Non-Specific, or TNAP.

When you have tests done to check your levels, they reveal levels for each different kind of phosphatase, which makes it easier for your medical practitioner both to diagnose and to treat any underlying conditions associated with an abnormal range.


What is Alkaline Phosphatase’s Normal Range?

The normal range is 20 to 140U/L, which might depend on the particular lab you use.

Pregnant women and children will have significantly higher levels (4).

If the results are high, your doctor will order further tests to determine if it’s bone or liver ALP that’s elevated.

This information can help identify a host of different disorders of the bones and liver.


What Can Increase Normal Levels?

There are a few different explanations for an increase in your normal levels.

When the doctor orders tests, they should help determine if the increase is due to a disorder or another cause.

Extended use of birth control pills can exponentially increase your levels, especially the longer you use them.

Because they interact with a woman’s reproductive hormones, they have the potential to increase the enzyme to many times the normal range.

Exercise can increase levels in the short term.

In a study done on male cyclists, it was shown that after 30 to 40 minutes of moderate to intense activity, levels increased, but quickly returned to normal during the rest period (5).

If you’ve been diagnosed with hyperthyroidism, you might also see your enzyme levels rise.

Thyroid hormone stimulates the production of the enzyme, and so those with thyroid issues are likely to see this increase.

Certain drugs and chemical compounds also show an increase in the enzyme.

The anti-HIV drug Efavirenz elevates enzyme levels, while also reducing bone density and causing a drop in vitamin D levels.

Omega-6 fatty acids also contribute to increases in enzyme levels.

A compound found in the grape family can also decrease the enzyme in those already susceptible.

It has been found to increase bone mineralization.

Even the body’s natural sex hormones can contribute to increased levels.

Estrogen and testosterone affect enzyme levels, and estrogen has even been shown to regulate the growth of the enzyme within the bone marrow.


What Can Decrease Normal Levels?

Fasting and starving have a significant effect on normal levels.

When you deprive yourself of food, the lining of the intestine begins to lose the enzyme.

Extended starving can decrease levels dangerously.

A low-protein diet can also mimic the effects of fasting and starving by decreasing enzyme levels.

The intestine is where the symptoms will appear.

Unlike omega 6 fatty acids, omega 3 fatty acids play a role in the decrease of the enzyme within the intestine.

The drug Cinacalcet, often prescribed for chronic kidney disease, can reduce levels up to 20 percent in long-term patients.

Resistance exercise, when performed by untrained males who aren’t used to such activity, can cause a short-term decrease in enzyme levels.

This decline is located in the bones and can occur two to three days after the exercise is performed (6).


Are there Specific Conditions that Increase Enzyme Levels?

Some conditions can increase the presence of enzyme levels in the body.

The enzymes are located in different areas, which can be indicative of certain diseases, and help physicians get closer to a diagnosis.

Let’s take a look at some different conditions that can cause an increase.

  • Bile duct obstruction is associated with increased enzyme levels. Increases of the enzyme in the liver may indicate a tumor that’s obstructing bile.
  • Certain kinds of cancers can cause increases. Breast cancer patients show elevated numbers during tests more frequently than healthy women (7). Elevated numbers can also indicate that cancer has metastasized (8). Liver cancer in connection with bile duct obstruction also causes increases. The presence of tumors in the liver is associated with elevated levels. Patients with metastasized colon cancer also show increased levels. It’s often correlated with an increase in cancer growth and may indicate that the cancer is spreading to the liver. Leukemia patients have unusually high levels, especially those with untreated or undiagnosed leukemia. The presence of placental enzymes is a useful marker for diagnosing the disease.
  • Alzheimer’s patients also have higher enzyme levels than healthy patients, although their levels are usually non-specific. There’s a direct inverse correlation between higher levels and lower brain function (9).
  • Paget’s disease patients have abnormally high levels of the enzyme in their bones. The disease affects bone strength and formation, and tests for the enzyme can show levels of bone turnover. Although the two are not directly related, the presence of the enzyme is a good indication of disease progression.
  • The hyperthyroid disease frequently elevates enzyme levels because the thyroid helps to regulate the presence of the enzyme in the body.
  • Heart disease is related to the levels of the enzyme in the body. The correlation isn’t completely understood, but based on studies higher levels correspond to higher instances of heart disease, strokes, heart attacks, and mortality after each of these health events (10).
  • The liver is still one of the most significant indicators of higher enzyme levels. Celiac disease is an autoimmune condition in which the body attacks the gut lining, causing inflammation. This inflammation also appears in other areas of the body, especially if patients do not follow the recommended treatments.
  • Sickle cell anemia patients have higher levels of the enzyme that corresponds to the damage within the bones and other tissues associated with the disease. It’s particularly associated with the vaso-occlusive crisis.
  • Epileptic patients, particularly children, have higher levels of the enzyme present in their system.
  • Celiac disease patients also have increased levels, as the body tries to counteract the inflammatory effects of certain gram-negative bacteria (11).


Are there Specific Conditions that Decrease Levels?

Other types of conditions are known to deplete levels of the enzyme or correlate with lower numbers.

Let’s take a look at some of these conditions.

  • Low levels of the enzyme are associated, and may cause, inherited conditions such as hypophosphatasia, in which bones and teeth are affected. The disease is marked by early loss of teeth and seizures in children. Adults have frequent dental problems and weakened bone structure. Achondroplasia and cretinism are both disorders involving growth. The first is a form of dwarfism that is associated with the absence of the enzyme at birth. The other causes severely stunted growth. In both, children that are tested for the enzyme show lower numbers than those of healthy children.
  • Wilson’s Disease patients show lowered numbers as well. The condition causes a buildup of copper in the organs. Patients had a low enzyme to bilirubin ratio.
  • Malnutrition also causes numbers to fall. Just like starving or fasting decreases numbers, chronic malnutrition can cause numbers to plummet if the condition is left untreated. In a study done recently of 130 patients showing low phosphatase numbers, 12% already suffered from malnutrition.


Benefits Associated with an Increase

There are a few benefits that are associated with the increase of the enzyme.

When no underlying conditions are present that need treatment, sometimes more enzyme can be a good thing for the body’s chemistry.

One of its most foundational purposes is to help with the mineralization of bones and teeth.

Mineralization builds up the layers of bone and teeth and prevents damage.

If the body is unable to make up for the natural loss of the surface layer, it can cause wearing of the tooth enamel and eventual tooth loss, and difficulties with the skeletal structure.

Children with chronically low numbers frequently have early loss of teeth and weakened bones.

Adults also have dental issues, though not always tooth loss, and weak bones.

In severe cases in infants, the decrease can cause critical seizures; in some extreme cases, death.

It’s essential for the survival of embryos when in the placental form and takes an active role in embryo development.

In a study done on mice, pregnant mice with low numbers had smaller litter sizes, fewer live births, and the offspring grew more slowly (13).

Low amounts of the enzyme correlate directly with issues with growth and development, and the soundness of bone and tooth structure.

Increasing your count is crucial if you have a condition that depletes the enzyme, or if you have a genetic disease associated with its loss or absence.


Benefits Associated with a Decrease

Just like numbers that are too high, numbers that are too low can cause issues.

However, when an underlying condition causes an unnatural increase in the enzyme and it interferes with the body’s natural processes, it’s helpful to decrease amounts.

A decrease in enzyme numbers is associated with better attention and memory.

Alzheimer’s patients show an increase in average levels, and bringing those numbers back down might help improve cognitive function.

It doesn’t mean the enzyme is harmful to the brain, but in some studies of weight loss surgery patients, patients did better on cognitive tests immediately following the surgery.

The link between the two is unclear, aside from the enzyme being an indicator.

There is a correlation between the cholesterol levels of pregnant women and the enzyme.

In tests, triglyceride and cholesterol levels increased in direct proportion to enzyme levels (14).

Although experts hesitate to link the results directly, they are hopeful that with more time, they will begin to understand the role of the enzyme in lowering cholesterol during pregnancy and at other times in life.


Other Benefits

Recent studies have begun to reveal the importance of the enzyme as associated directly with the gut lining.

It interacts with our food as we digest it.

We are only just beginning to understand how this gut enzyme works with bacteria and flora in the digestive system to process food fully, and either cause or relieve symptoms associated with other, more severe, conditions.

Studies are showing some benefits due to the increase in these levels, but there are currently no commercially-available supplements.

Curcumin has been shown to increase levels naturally and may benefit some patients who are looking to improve levels without medical intervention.

Let’s take a look at what studies are beginning to show us about this little-known enzyme within the gut lining.


Protects Against Bacterial Infection

Conditions like celiac disease, plus other food sensitivities, cause an increase in inflammatory chemicals inside the gut lining.

Too much inflammation and the body has a difficult time healing itself which is why when you eat foods that cause inflammation, the condition worsens.

Many of these inflammatory substances are gram-negative bacteria.

Gram-negative bacteria have a lining made of lipopolysaccharides (LPS) that triggers massive infections, such the abovementioned chronic inflammation or, in the worst case, sepsis.

Phosphatase within the gut lining binds to these inflammatory chemicals and removes LPS.

This reduces inflammation. In some studies, it even controlled cellular resistance to LPS (15).

In other types of gut infections, the enzyme played a part in stopping certain kinds of bacteria from traveling through the intestine before they could wreak havoc.


Helps to Restore Healthy Flora After Antibiotic Use

Antibiotics are a necessary evil, at times.

We take them to help treat infections, but they don’t always distinguish between good and bad bacteria.

Extended antibiotic use, or in some cases usage in those who are particularly sensitive, removes the normal flora from the gut and causes dietary issues and inflammation.

There are things you can do to help rebuild this flora, and studies are showing that ALP can help restore them more efficiently.

In two different studies, mice were given supplements of the enzyme and then either exposed to bad bacteria (salmonella and Clostridium) or given supplements during antibiotic treatments.

In the first experiment, mice with compromised flora were given the supplement before infection.

They showed more resistance to the bad bacteria than mice without supplementation, suggesting a correlation between the enzyme and rapid rebuilding of gut flora.

In a second experiment, mice were supplemented with the enzyme from a calf’s intestinal lining during a course of antibiotics.

Mice with the supplement showed fewer infections and lower mortality rates than mice without the supplementation (16).


Repairs Leaky Gut

Leaky gut means that there are small perforations in the walls of the gut lining.

These perforations allow microscopic bacteria and other chemicals to leak through the walls and cause inflammation in the surrounding tissue and organs.

Patients with cystic fibrosis have higher instances of leaky gut because the disease decreases the soundness of the gut lining and increases its permeability over time.

Patients with this disease also show less enzyme activity.

Studies done on mice with cystic fibrosis showed some benefit with supplementation in improving the gut barrier (17).

It helped to improve the quality of the gut lining, and also helped reduce bacterial overgrowth associated with leaky gut.


Helps Remove Toxins from the Gut Lining

In addition to the enzyme’s work to reduce inflammation associated with bad bacteria and toxins within the gut lining, the enzyme also helps to eradicate those toxins.

It removes the phosphate groups from leftover DNA strands and parts of bad bacteria that react poorly with the gut lining.


Helps Reduce Gut Inflammation in At-Risk Infants

Infants who are suffering from necrotizing enterocolitis have shown some response to supplementation with the enzyme.

Though it doesn’t cure the condition, it has been shown to reduce and slow inflammatory molecules associated with gut cell death.


Slows Fat Absorption

Mice lacking the enzyme absorb fat very quickly.

When they were supplemented with the enzyme, it slowed the absorption of fat, regulating weight gain and blood cholesterol levels (18).

All these factors contribute to the enzyme’s role in the gut and overall digestive health.


Improves Kidney Function

Severe bacterial infections in the kidneys are associated with inflammation and the inability to process toxins, leading to sepsis and, if left untreated, death.

Supplementing with the enzyme by introducing it into the blood correlated with lower levels of infection and improved kidney function (19).

This is because the enzyme helps to reduce toxins from the permeated gut lining and protect the surrounding organs from the subsequent inflammatory response.

When the enzyme removes phosphates from the offending particles, it reduces the body’s reaction to the presence of the bacteria.


Protects Against Type-2 Diabetes

Type 2 diabetes is a physical response to the body’s increasing inability to process and respond to sugars.

Mice with the condition showed lowered levels of the enzyme in the gut and bloodstream.

Scientists studied the stools of both Type-2 diabetes and healthy patients and found that compared to the control group, those with the disorder showed consistently lower levels of the enzyme (20).

In subsequent studies in mice, supplementation correlated with protection in mice that had a high-fat diet (21).

It also showed some benefit in protecting obese patients from developing further digestive and endocrine-related issues.



If your doctor suspects any of the conditions listed in this guide, or if you know you have a family history of one or more of them, it may be helpful to undergo further testing to check your enzyme levels.

Although many of the levels only correlate to the listed conditions or disorders, your numbers may help medical professionals pinpoint a specific disorder’s severity or progression.

They are often indicative that certain types of cancers have metastasized, or that there is an issue with gut lining and digestive processes.

The tests break down exactly what type of enzyme is showing abnormal numbers, and you and your doctor can decide on the best course of action.

If you’ve already received an abnormal test result, you may want to evaluate your current biological and lifestyle conditions.

Some of the results may be temporary, due to factors like birth control use or doing certain kinds of exercise.

Don’t try to increase or lower your numbers yourself.

It’s essential that you work on the underlying conditions if there are any before you begin to target the enzyme level directly.

Adverse reactions to changing levels can occur if you don’t approach it from a holistic perspective that treats all the possible causes without doing so excessively.

Right now, you can make sure that you are getting a wide range of nutrients from quality, healthy foods, and that you are exercising appropriately for your health.

These will give you a solid foundation to treat conditions and abnormal test levels in conjunction with your doctor.

Do you have any further questions about this often-overlooked enzyme?

Let us know in the comments below.

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