Intestinal Alkaline Phosphatase is Found on the Cells that Line the Gut as Well as Inside the Gut and the Gut Immune Cells, source: https://www.ncbi.nlm.nih.gov/pubmed/25400448

40 Facts about Alkaline Phosphatase and How You Can Optimize this Powerful Enzyme

Alkaline phosphatase is a group of very important enzymes, including intestinal alkaline phosphatase, tissue non-specific alkaline phosphatase, and placental alkaline phosphatases. Read this post to learn more about the roles of alkaline phosphatase and how you can optimize this enzyme.

Contents

Introduction

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Alkaline phosphatase is an enzyme that dephosphorylates (removes phosphate groups from) other molecules such as proteins and nucleotides. They are found in all body tissues in the human body but are mostly concentrated in the bones, kidneys, liver, intestines, and placenta (R).

Four different genes encode human alkaline phosphatases, i.e. (R):

  • ALPI for the alkaline phosphatase in the intestine
  • ALPP for the alkaline phosphatase in the placenta
  • ALPPL2 for the placenta and cells that would become eggs and sperms
  • ALPL (also called TNAP for Tissue Non-Specific Alkaline Phosphatase) for the alkaline phosphatase in the liver, bone, and kidney

The correct balance of alkaline phosphatase is required for healthy functioning, too much or not enough can cause a broad range of diseases (R). Genetic mutations can have an impact on this balance leading to the development of disorders. Go to SelfDecode to learn how to get your own genetic information evaluated for alkaline phosphatase risk.

Not much is known about its function in most tissues of the body. However, it does play an important role in the development of bones and teeth, because it is essential for mineralization. Mineralization is when minerals, like calcium and phosphorus, are deposited in bones and teeth to help them become strong (R).

Alkaline phosphatase is used in ongoing research on stem cells, cancer, and other diseases. This enzyme is also used in the dairy industry because it is an indicator for pasteurization (R).

Blood Test for Alkaline Phosphatase

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Generally, the total alkaline phosphatase (ALP) test is run to find all types of ALP in the blood to diagnose bone and liver disorders.

If ALP comes back high, the doctor may order the ALP isozyme test to see which specific type of alkaline phosphatase is elevated. The ALP isozyme test can distinguish between the bone and liver ALP (R).

The normal range of alkaline phosphatase in blood is 20 to 140U/L, although this can vary from lab to lab. Children and pregnant women can have significantly higher levels of the enzyme in their blood (R).

The Roles of Alkaline Phosphatase

Intestinal Alkaline Phosphatase

Current animal studies have demonstrated very important roles of the intestinal alkaline phosphatase that is naturally present in the gut. The enzyme interacts with the gut, the food we eat, and the microbes found in our body.

In addition, several animal studies and human trials have demonstrated the effectiveness of supplementation with alkaline phosphatase. However, currently, there is no alkaline phosphatase supplement available for sale.

Unlike other types of alkaline phosphatases, intestinal alkaline phosphatase is mostly tied to the gut lining, with 1 – 2% may be present in the bloodstream (R).

1) Alkaline Phosphatase Protects Against Bacteria Infection in the Gut

Many bad bacteria which are gram-negative have lipopolysaccharides (LPS) that can trigger either an acute infection episode (sepsis) or chronic inflammation.

Intestinal alkaline phosphatase can remove phosphate groups from LPS, which reduces its inflammatory effects (R).

In addition, intestinal alkaline phosphatase also prevents the bacteria like Salmonella typhimurium and Clostridium difficile from traveling to the lymph notes in the gut (R).

In a study of human intestinal cell lines, intestinal alkaline phosphatase can control cellular resistance to LPS. The presence of LPS in the blood can stimulate inflammation in the body (R).

2) Alkaline Phosphatase Helps Restore Gut Bacteria After Antibiotics

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Treating selfdecode.com/?utm_source=seo&utm_medium=selfhacked&utm_campaign=id00002″>selfdecode.com/health-effect/antibiotic/?utm_source=seo&utm_medium=selfhacked&utm_campaign=id00002″ target=”_blank”>antibiotic-treated mice with intestinal alkaline phosphatase (IAP) before Salmonella and Clostridium infection protects the mice from the infection, suggesting that IAP helped to rapidly restore gut flora.

In mice, oral supplementation with calf IAP during antibiotic treatment had fewer infections and a lower mortality rate compared to mice with no supplementation (R).

3) Alkaline Phosphatase Helps Repair Leaky Gut in Cystic Fibrosis Patients

Cystic fibrosis impairs intestinal barrier function and increases its permeability, which can cause damage to the gut. This also causes reduced activity of intestinal alkaline phosphatase (R).

In mice with cystic fibrosis, intestinal alkaline phosphatase administration from an outside source helped improve intestinal permeability. It also reduced small intestinal bacterial overgrowth by more than eighty percent (R).

4) Intestinal Alkaline Phosphatase Help Removes Toxic Microbial Chemicals

Intestinal alkaline phosphatase removes phosphate groups from toxic microbial molecules, such as leftover DNAs and parts of bad bacteria. This role of IAP helps protects us against from inflammation (R).

5) Intestinal Alkaline Phosphatase Slows Down Fat Absorption

Mice without intestinal alkaline phosphatase absorb fat very fast. As a result, these mice have higher blood lipids and gain weight faster than normal mice (R).

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How the Intestinal Alkaline Phosphatase Mediates the Interplay between the Gut Bacteria and the Gut to Protect Against Inflammation and Oxidative Stress. Source:https://jasbsci.biomedcentral.com/articles/10.1186/s40104-016-0123-7

6) Alkaline Phosphatase Helps Treat Kidney Injuries

In humans with severe bacteria infection, the administration of alkaline phosphatase through the blood helped improve overall kidney function. It improved creatinine clearance in the patients and lessened the duration or even the requirement for renal replacement therapy (R).

Because alkaline phosphatase can reduce inflammation by removing phosphate groups from certain toxins, it can protect organs from bacterial damage (R).

7) Alkaline Phosphatase Protects Against Type 2 Diabetes

Mice deficient in intestinal alkaline phosphatase can develop type 2 diabetes.

Oral supplementation of intestinal alkaline phosphatase prevents metabolic syndrome in mice fed with high fat diet (R).

Scientists studied the stools of 200 diabetic and 400 non-diabetic patients. They found that compared to the controls, diabetic patients had lower intestinal alkaline phosphatase activity levels (R).

Intestinal alkaline phosphatase was also protective against type 2 diabetes even in obese patients (R).

8) Intestinal Alkaline Phosphatase Helps with Gut Cell Deaths in Newborns

Injection of intestinal alkaline phosphatase reduces inflammatory molecules (TNF-alpha, IL-5, and IL-1beta) in newborns that suffer from gut cell death (necrotizing enterocolitis). However, the injection did not cure the necrotizing enterocolitis (R).

Other Types of Alkaline Phosphatase

9) Embryonic Alkaline Phosphatase is Required for Embryonic Development

While its specific function during embryonic development is unknown, the absence of its gene affects the development and survival of embryos (R).

Placental alkaline phosphatase, together with calcium, insulin, and zinc-backed-science/” target=”_blank”>zinc, works like a growth factor (to stimulate growth) for human embryonic cells in cell-base study (R).

Although its specific functions are unknown, it is a positive regulator of fetus growth (R).

Embryonic alkaline phosphatase is found in mouse embryo before the embryo implants into the mother’s uterus (R).

Compared to normal mice, mice with mutated embryonic alkaline phosphatase had a smaller litter size, fewer embryonic cells, and grew more slowly (R).

10) Bone Alkaline Phosphatase is Essential for Bone Growth

The mineralization of bone and teeth require this enzyme (R).

A genetic mutation in bone alkaline phosphatase results in defective bone mineralization, leading to early loss of teeth, frequent dental problems and weakened bones. In more severe cases, this can cause seizures and infant deaths.

Without this important enzyme, children can have early loss of teeth while adults can have dental problems and weakened bones. The most severe cases of hypophosphatasia can cause seizures or infant deaths (R).

Decreased Levels of Alkaline Phosphatase

Reduced levels are correlated with certain diseases (R).

1) Hypophosphatasia

Low levels of alkaline phosphatase can cause hypophosphatasia, an inherited disorder that causes defective bone mineralization. Without the enzyme, children can have early loss of teeth and seizures while adults can have dental problems and weakened bones (R).

2) Wilson’s Disease

Wilson’s disease is an inherited disorder where copper is accumulated in the organs. Wilson’s disease patients have low blood alkaline phosphatase activity. They also had significantly a lower alkaline phosphatase to bilirubin ratio (R).

3) Achondroplasia and Cretinism

Achondroplasia is a type of dwarfism, and cretinism is a condition with severely stunted growth. In children with these disorders, their alkaline phosphatase levels are lower than normal range (R).

4) Malnutrition

Malnutrition can also cause lowered alkaline phosphatase levels in the blood. In a review of 130 patients with low enzyme levels, 12% suffered from malnutrition (R).

When Low Alkaline Phosphatase may be Good

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1) Lower Alkaline Phosphatase May Predict Better Attention and Memory Abilities

Decreased alkaline phosphatase levels predicted better scores on a brain test in patients who have undergone weight loss surgery. This suggests that a lower level of enzyme activity can predict better attention and memory abilities. However, this does not prove that the enzyme is harmful to the brain (R).

2) Higher Blood Lipids in Pregnant Women are Associated with Higher Alkaline Phosphatase

Pregnant women have higher blood alkaline phosphatase activity. Both triglyceride and total cholesterol levels increased in parallel with alkaline phosphatase, so cholesterol levels are correlated with enzyme activity (R).

Elevated Levels of Alkaline Phosphatase

While alkaline phosphatase may not necessarily cause harm to the body itself, elevated levels are associated with cancer, bone, liver, and kidney diseases (R).

1) Biliary Obstruction and Liver Cancer

High liver alkaline phosphatase levels are associated with bile duct obstruction and liver cancer. The presence of liver alkaline phosphatase in patients may indicate the presence of a tumor in the bile duct (R).

2) Colon Cancer

Alkaline phosphatase levels are frequently high in patients with metastatic colon cancer. Increasing alkaline phosphatase levels are correlated with increasing cancer stage and may indicate that the cancer has spread to the liver (R).

3) Breast Cancer

Women with breast cancer had elevated levels of alkaline phosphatase compared to normal healthy women. The increase of enzyme activities also indicates that the cancer is metastatic and spread to either the bone or liver (R, R).

4) Leukemia

Leukemia patients, especially untreated ones, have high alkaline phosphatase levels. The placenta alkaline phosphatase level is a useful biomarker to help diagnose and treat leukemia (R).

5) Alzheimer’s

Alzheimer’s patients have higher tissue-nonspecific alkaline phosphatase levels compared to healthy patients. The higher the alkaline phosphatase activity, the lower the brain function (R).

6) Hyperthyroidism

Increased alkaline phosphatase levels are also correlated with hyperthyroidism (R).

7) Paget’s Disease

Paget’s disease is a common disorder that affects bone strength and formation. Abnormally high levels of bone alkaline phosphatase can be an indicator of bone turnover, so while the enzyme does not cause the disease, it can be a helpful indicator (R, R).

8) Vitamin D Deficiency

Vitamin D deficiency is usually accompanied by elevated levels of total alkaline phosphatase in the blood. However, it is not the best indicator for vitamin deficiency (R).

9) Heart Disease

Elevated alkaline phosphatase levels are associated with a higher risk for heart disease.

In a prospective study of more than 3000 elderly men, the higher alkaline phosphatase levels predict higher risks of heart attacks, strokes, and increase mortality (R).

10) Liver Problems Associated with Celiac Disease

Celiac disease is an autoimmune condition where the immune system attacks the gut lining upon gluten consumption. In cases of uncontrolled celiac disease where the patients continue to consume gluten, other liver and biliary tract disorders can occur. Elevated alkaline phosphatase levels are associated with these two disorders (R).

11) Sickle Cell Anemia

Sickle cell anemia is associated with high levels of alkaline phosphatase. The higher alkaline phosphatase levels correlate with worsened bone and other tissue damage in sickle cell anemia patients (R, R).

12) Epilepsy

Epileptic children have higher alkaline phosphatase levels compared to children without the disorder (R).

Factors that Increase Alkaline Phosphatase Levels

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1) Oral Contraceptives

Oral contraceptives (birth control pills) can increase alkaline phosphatase to many times the level of a normal range (R).

2) Exercise

While exercise increases bone alkaline phosphatase levels after thirty and fifty minutes of moderate to intensive exercise in male cyclists, before quickly returning to normal (R).

2) Efavirenz

Efavirenz, an anti-HIV drug, is associated with increased alkaline phosphatase levels in HIV patients. The high enzyme levels also associated with increased bone turnover and Vitamin D deficiency (R).

3) Cissus quadrangularis

Cissus quadrangularis, a type of plant from the grape family, significantly increases alkaline phosphatase activity in cell culture. It also increases bone mineralization, which is likely due to the increased enzyme function (R).

4) Curcumin

Curcumin increases intestinal alkaline phosphatase activity levels in gut cells (R).

Factors that Decrease Alkaline Phosphatase Levels

1) Starvation and Fasting

Starvation causes the loss of intestinal alkaline phosphatase (R).

2) Omega-3 Fatty Acids

Omega-3 fatty acids reduce the levels of intestinal alkaline phosphatase, whereas omega-6 fatty acid increases the level of intestinal alkaline phosphatase in the gut (R).

3) Cinacalcet

Cinacalcet, a drug for chronic kidney disease, can reduce blood alkaline phosphatase levels by more than twenty percent in patients after 26 weeks administration (R).

Factor that Increases Alkaline Phosphatase Activities

Estrogen and Testosterone Metabolites

Estrogen, 5 alpha-dihydrotestosterone, and dehydroepiandrosterone (different types of hormones) can increase the enzyme’s activity in human endometrial cancer cell lines (R).

Estrogen is also able to regulate the growth and expression of this enzyme in human bone marrow cell culture (R).

Factors that Decrease Alkaline Phosphatase Activities

1) Magnesium Deficiency

Magnesium deficiency can lower alkaline phosphatase activity levels in the body because The enzyme needs magnesium to activate. In a study done on female rats, the rats with a magnesium-deficient diet had only half the alkaline phosphatase activity compared to the controls. Magnesium supplementation significantly restores enzymatic activity, but it did not return to normal levels (R).

2) Resistance Exercise

In untrained male subjects, one single bout of resistance exercise can cause bone ALP activity to significantly decrease two and three days after the exercise (R).

3) Protein-Free Diet

Rats fed a protein-free diet have reduced intestinal alkaline phosphatase activity (R).

Technical

  • Alkaline phosphatase has four different isozymes. Isozymes are different enzymes that have the same function but a different structure (R).
  • Its four isozymes are placental ALP, intestinal ALP, germ cell ALP, and liver/kidney/bone ALP (or tissue-nonspecific ALP). These isozymes depend on the site of the tissue of the enzyme expression (R).
  •  The bone isoenzyme may be involved in mammalian bone calcification.  The intestinal isoenzyme may play a role in the transport of phosphate into epithelial cells of the intestine (R).
  • The mean gestation length was 12.72 hr longer in the homozygous 129P3-EAP.ko mice than in the 129P3 (control) mice (R).
  •  In addition, there was an increasing percentage of degenerated embryos in the EAP.ko group, that plateaus at 96 hr with 62% embryo mortality (R).
  • Mice are treated with amoxicillin +/− cIAP followed by S. Typhimurium gavage and there was a higher number of S. Typhimurium translocated to the MLN, liver and spleen in the cIAP− animals compared to the animals of the cIAP+ group (R).
  • It is evident that the cIAP+ group rapidly cleared their toxins, whereas all of the animals in the cIAP− group still had toxins in their stool (R).
  • In patients with sickle cell disease, higher levels of alkaline phosphatase may be due to associate vasocclusive crises involving the bones (R).

Comments

  1. Kathy P.

    I’d like to hear your response to the previous comment/question from ADAM C. I have the same situation – consistently low ALP level (10 years +) and Hashimoto’s thyroiditis. I also have low vitamin D even though I take a D3 supplement daily.
    Are all of these things related? And what can I do to raise my ALP?

  2. Adam C

    I consistently have below range ALP. I also have Hashimoto’s thyroiditis. What can I take to raise my ALP? Will N-acetyl Cysteine help? Thanks

  3. Alice Aman

    If I’m reading this right (and I scanned it quickly), seems that high ALP in some cases is very good and in other cases is very bad. Kind of confusing. Wish you had some kind of matrix or something that had rows of “conditions/diseases” and columns of “desirable level” i.e. high or low?

    • Nattha Wannissorn

      Thanks for the comments, Alice. Gut ALP is very important, so it’s important to have enough.
      Whereas, liver ALP and non-tissue specific ALP is typically only elevated where there is liver and tissue damage. We’ll definitely consider including a table for this post and the next ones. ~Nattha @ Team SelfHacked

  4. pamojja

    Though can’t remember where, heard a consistent ALP below 70 would indicate Zinc deficiency. In my case seems could be the case, since recent intake above 50mg/d correlated with an ALP of about 90, while below 50 mg/d of Zinc it averaged at 70 for many years.

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