Alkaline Phosphatase: Diagnostic Significance and Clinical Insights

Authors: Payal Bhandari, M.D.

Contributors: Hailey Chin, Vivi Chador



Alkaline Phosphatase 


Alkaline phosphatase is a critical enzyme that plays a crucial role in bone formation and mineralization. It is typically produced in the liver, bile duct, and bone cells. 


Abnormal levels can signify liver damage, bile duct obstruction, and bone issues, such as rickets or bone tumors. 




Typical Adult Range


Ranges and thresholds can vary due to: 

(1) Lab-specific equipment, techniques, and chemicals, and 

(2) Patient demographics, including age, sex, and ethnicity.




Key Insights

The liver is a crucial organ that helps with many processes in the body, such as breaking down substances, storing nutrients, and controlling blood clotting. It also plays a role in detoxifying the body, providing energy, and managing immune responses. One important lab test for liver health is the alkaline phosphatase (ALP) biomarker, which helps doctors assess liver function. High ALP levels can indicate liver problems, such as inflammation, fatty liver disease, or scarring (cirrhosis), which may not show clear symptoms until they’re severe. Certain medications can also increase ALP levels by stressing the liver. Monitoring ALP regularly, along with other tests, helps doctors spot issues early, track treatment progress, and manage side effects. Lifestyle changes and a healthy diet can help reduce ALP levels and prevent serious health problems.


What is Alkaline Phosphatase?

Enzymes are proteins that speed up chemical reactions in the body. They help build tissues, move substances, and support other processes. Without them, reactions would be too slow to keep us alive. Alkaline phosphatase (ALP) is an enzyme important for bone health. It helps add minerals like calcium and phosphorus to bones, making them strong. ALP also helps absorb phosphorus, which is needed for energy and healthy cells. ALP is also a marker for problems like tissue injury, inflammation, cancer, bone diseases, and heart conditions. Healthy ALP levels are essential for good health.



Figure 1: Alkaline phosphatase is important for energy production, bone health, cell communication, and fluid balance. It helps the body absorb and store phosphorus, which is key for energy and cell function. The enzyme also helps phosphorus bind to fat molecules, protecting cells and regulating important processes. Phosphorus also helps balance fluids and control minerals like calcium, sodium, and potassium, which are essential for health.


Regulation of Alkaline Phosphatase Levels in the Body

Alkaline phosphatase (ALP) levels are controlled by the liver, bones, small intestine, and kidneys. ALP production is influenced by phosphorus in your diet, found in:

  • Seeds: Sunflower, chia, flaxseeds

  • Nuts: Almonds, cashews, walnuts

  • Legumes: Lentils, chickpeas, black beans, soy (tofu, edamame)

  • Whole grains: Quinoa, oats, brown rice, whole wheat

  • Vegetables: Potatoes, broccoli, Brussels sprouts

  • Nutritional yeast: High in phosphorus and B vitamins

After eating, ALP helps absorb phosphorus in the intestine and send it to the bloodstream. The kidneys filter and reabsorb most phosphorus, excreting a small amount in urine.

Two hormones control ALP and phosphorus: parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23). PTH is released when calcium is low and increases calcium absorption while causing phosphorus to be excreted. FGF23 is released when phosphorus is high, lowering vitamin D and increasing phosphorus loss. Both hormones raise ALP levels but lower phosphorus, calcium, magnesium, vitamin D, and energy balance.



Figure 2: Calcium and phosphorus control alkaline phosphatase (ALP) production. When bone activity increases, it raises calcium levels and boosts ALP. ALP helps absorb phosphorus in the intestines, which then goes into the blood, is filtered by the kidneys, and stored in bones and muscles. Low calcium levels trigger hormones that increase phosphorus loss in urine and lower ALP.


Clinical Significance of High Alkaline Phosphatase Blood Levels 

Atherosclerosis

High alkaline phosphatase levels can be a concern, especially for people with liver issues. The kidneys control phosphorus levels, but when they’re damaged, phosphorus builds up in the blood. This triggers the release of parathyroid hormone (PTH), which pulls calcium from bones, weakening them and raising the risk of fractures and joint problems.

As calcium rises in the blood, it triggers more alkaline phosphatase release, causing calcium to build up in damaged cells and blood vessels. This narrows blood vessels, raises blood pressure, and contributes to atherosclerosis (plaque buildup in arteries).

Atherosclerosis affects energy use in the body by:

  • Turning glucose into the main energy source and storing fat.

  • Breaking down muscle protein for energy, increasing blood acidity and ROS.

  • ROS damage cells, causing LDL fat to stick to walls and reduce blood loss.

  • White blood cells clean up damage, release inflammatory proteins, and form clots, scar tissue, and new blood vessels.


Figure 3: Atherosclerosis is when fat, calcium, and scar tissue build up in the arteries, causing them to harden. This reduces blood flow, raises blood pressure, and causes inflammation. As blood backs up into organs like the heart and legs, they enlarge and lose function. White blood cells and damaged cells try to control the inflammation and prevent bleeding.


  

Elevated alkaline phosphatase levels in the blood can signal changes in metabolism. This leads to more undigested food particles in the bloodstream, which makes it harder for red blood cells to deliver oxygen and remove waste from tissues (hypoxia). When cells can’t function properly, they become more likely to be damaged, which can cause abnormal cell growth or allow harmful microorganisms like bacteria and viruses to thrive. Additionally, this can speed up the buildup of plaque in the arteries, leading to overactive white blood cells and platelets. This can cause the body to produce antibodies that attack its own tissues, triggering autoimmune diseases (like Crohn’s, celiac disease, and rheumatoid arthritis), excessive clotting, infections, cancer, and even organ failure.


                          

Figure 4: High alkaline phosphatase levels are linked to chronic inflammation, gut health issues, and the growth of cancer cells. Platelets help tumors and pathogens by collecting iron and hemin from damaged cells, feeding them and aiding their spread. Neutrophils protect blood vessels but also stop immune cells from attacking tumors and pathogens. This helps tumors grow new blood vessels. Overall, white blood cells release chemicals that allow harmful organisms to steal nutrients, cause infections, and support tumor growth.




Figure 5: High alkaline phosphatase levels are linked to inflammation that harms organs and causes health issues. In the brain, it can lead to confusion, seizures, or coma. In the digestive system, it affects nutrient absorption and can cause nausea, vomiting, and pain. In bones, it increases fragility, leading to fractures and pain. In the kidneys, it can cause frequent urination and blood in the urine. In the heart, it raises blood pressure and increases the risk of heart attack and stroke.


Clinical Significance of Low Alkaline Phosphatase Blood Levels 

Low alkaline phosphatase (ALP) levels can disrupt the balance of phosphorus and calcium in the body. This can lower energy production and cause fluid imbalances, putting stress on organs. For example, less blood flow to the kidneys increases phosphorus loss, worsening the deficiency and damaging cells.

In septic patients, low ALP levels are linked to high levels of inflammatory proteins. A 1998 study found that 80% of septic patients had low ALP, especially those with harmful microorganisms and inflammatory proteins. Sepsis changes how the body uses energy and increases cell damage. Kidney damage leads to more phosphorus loss, lowering ALP production and causing problems with brain and nerve function. Low ALP also weakens bones, increasing the risk of fractures and joint problems. It can lead to blood vessel stiffness, high blood pressure, and organ failure.

Conclusion

Maintaining healthy alkaline phosphatase (ALP) levels is important for overall health. ALP helps with energy, fluid balance, nerve function, and the health of the heart, bones, and brain. If ALP levels are too high or too low, it can cause symptoms like joint pain, bone pain, fatigue, muscle breakdown, brain problems, high blood pressure, and heart irregularities. These imbalances can lead to serious health issues, such as heart attack, stroke, autoimmune disorders, cancers, infections, and organ failure. To keep ALP levels in check, try eating a nutrient-rich, plant-based diet with plenty of fruits, vegetables, and legumes. Drink enough water, limit alcohol and tobacco, avoid drugs that harm the liver or kidneys, and manage stress. These steps can help prevent severe health problems.


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