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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.

What is Alkaline Phosphatase?

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 [1].

There are different forms of the enzyme. The bone form is involved in bone calcification. The intestinal form plays a role in the transport of phosphate into intestinal cells (epithelial) [1].

The correct balance of alkaline phosphatase is required for healthy functioning, too much or not enough can cause a broad range of diseases [2].

Alkaline phosphatase plays 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 [1].

Alkaline phosphatase is used in ongoing research on stem cells, cancer, and other diseases [3].

Normal Range for Alkaline Phosphatase

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.

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 [1].

Conditions With Decreased Alkaline Phosphatase

Reduced levels are correlated with certain diseases [4].

1) Hypophosphatasia, Achondroplasia, and Cretinism

Low levels of alkaline phosphatase can cause hypophosphatasia, an inherited disorder that causes defective bone mineralization. Without the enzyme, children can have an early loss of teeth and seizures while adults can have dental problems and weakened bones [5].

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 the normal range [6].

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 a significantly lower alkaline phosphatase to bilirubin ratio [7].

3) 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 [8].

Benefits of Decreased Alkaline Phosphatase

1) 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 [9].

2) Lower Cholesterol (correlation)

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 [10].

Conditions with Increased 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 [5].

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 [11].

2) Colon Cancer

Alkaline phosphatase levels are frequently high in patients with metastatic colon cancer. Increasing alkaline phosphatase levels are correlated with an increased cancer stage and may indicate that cancer has spread to the liver [12].

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 [13, 14].

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 [15].

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 [16].

6) Hyperthyroidism

Increased alkaline phosphatase levels are also correlated with hyperthyroidism [17]. Thyroid hormones stimulate alkaline phosphatase [18, 19].

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 [20, 20].

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 of vitamin D deficiency [21].

9) Heart Disease

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

In a prospective study of more than 3,000 elderly men, the higher alkaline phosphatase levels predict higher risks of heart attacks, strokes, and increase mortality [22].

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 [23].

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 [24, 25].

In patients with sickle cell disease, higher levels of alkaline phosphatase are associated with vaso-occlusive crises involving the bones [25].

12) Epilepsy

Epileptic children have higher alkaline phosphatase levels compared to children without the disorder [26].

Benefits of Increased Alkaline Phosphatase

Alkaline phosphatase helps with bone and teeth mineralization [5].

A genetic mutation in bone alkaline phosphatase results in defective bone mineralization, leading to early loss of teeth, frequent dental problems and weakened bones.

Without this important enzyme, children can have an 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 [5].

Alkaline phosphatase is important for the development and survival of embryos (27). It causes fetal and embryonic cell growth (28). Mice with mutated embryonic alkaline phosphatase had a smaller litter size, fewer embryonic cells, and grew more slowly (27).

Factors that Increase Alkaline Phosphatase

1) Birth control pills

Birth control pills can increase alkaline phosphatase to many times the level of a normal range [29].

2) Exercise

Exercise increases bone alkaline phosphatase levels after thirty and fifty minutes of moderate to intensive exercise in male cyclists, but it quickly returns to normal [30].

3) Thyroid Hormones 

Thyroid hormones stimulate alkaline phosphatase [18, 19]. Increased alkaline phosphatase levels are also correlated with hyperthyroidism [17].

4-5) Efavirenz and Cissus quadrangularis

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 [31].

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 [32].

Estrogen and Testosterone Metabolites

Estrogen, 5 alpha-DHT, and dehydroepiandrosterone (different types of hormones) can increase the enzyme’s activity (not the level in the blood) in human endometrial cancer cell lines [33].

Estrogen is also able to regulate the growth and expression of this enzyme in human bone marrow cell culture [34].

Factors that Decrease Alkaline Phosphatase

1) Starvation and Fasting

Starvation and fasting causes the loss of intestinal alkaline phosphatase [35].

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 [36].

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 [37].

4) Magnesium Deficiency (decreases activity)

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 [38].

5) Resistance Exercise (decreases activity)

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 [39].

6) Protein-Free Diet (decreases activity)

Rats fed a protein-free diet have reduced intestinal alkaline phosphatase activity [40].

8 Benefits of 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 [41].

Curcumin increases intestinal alkaline phosphatase activity levels in gut cells [42].

1) 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 [35].

In addition, intestinal alkaline phosphatase also prevents bacteria like Salmonella typhimurium and Clostridium difficile from traveling to the lymph nodes in the gut [43].

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 [35].

2) Helps Restore Gut Bacteria After Antibiotics

Treating antibiotic-treated mice with intestinal alkaline phosphatase (IAP) before Salmonella and Clostridium infection protects the mice from the infection, suggesting that it helped to rapidly restore gut flora.

In mice, oral supplementation with calf intestinal alkaline phosphatase during antibiotic treatment had fewer infections and a lower mortality rate compared to mice with no supplementation [44].

3) 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 [45].

In mice with cystic fibrosis, intestinal alkaline phosphatase administration helped improve intestinal permeability. It also reduced small intestinal bacterial overgrowth by more than eighty percent [45].

4) Helps Remove Toxic Microbial Chemicals

Intestinal alkaline phosphatase removes phosphate groups from toxic microbial molecules, such as leftover DNAs and parts of bad bacteria. This helps protect against inflammation [46].

5) Slows Down Fat Absorption

Mice without intestinal alkaline phosphatase absorb fat very fast. As a result, these mice have higher blood cholesterol and gain weight faster than normal mice [47].

6) Helps Treat Kidney Injuries

In humans with a severe bacterial infection, the administration of alkaline phosphatase through the blood helped improve overall kidney function [48].

Because alkaline phosphatase can reduce inflammation by removing phosphate groups from certain toxins, it can protect organs from bacterial damage [48].

7) 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 [49].

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 [50].

Intestinal alkaline phosphatase was also protective against type 2 diabetes even in obese patients [50].

8) Helps Reduce Gut Inflammation

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 [51].

Genetics of Alkaline Phosphatase

Different genes encode human alkaline phosphatases, i.e. [1]:

  • ALPP for the alkaline phosphatase in the placenta
  • ALPL (also called TNAP for Tissue Non-Specific Alkaline Phosphatase) for the alkaline phosphatase in the liver, bone, and kidney

Go to SelfDecode to learn how to get your own genetic information evaluated for alkaline phosphatase risk.

Irregular Alkaline Phosphatase Levels?

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