High lactate dehydrogenase is your body’s alarm bell: it signals something is not quite right. It is an unspecific cue: pointing to tissue damage from many possible conditions. The test was once used to diagnose heart attacks, while recent research reveals this enzyme can be used to predict cancer survival. Read on to learn what the normal range is and what your levels mean.

What is Lactate Dehydrogenase (LDH)?

Lactate dehydrogenase (also known as lactic acid dehydrogenase, LDH, or LD) is an enzyme found in almost all living things. It plays an important role in energy production in the body [1].

More specifically, LDH helps convert lactate to pyruvate or pyruvate to lactate. This, in turn, leads to more conversion between NAD+ and NADH, which store energy. NADH is used to create ATP, the energy currency of the cells [1].

LDH is found in most tissues of the body. Whenever your cells are damaged or destroyed, the LDH inside them can leak into the bloodstream [2].

This makes LDH a useful tool for identifying tissue injury or breakdown. Some conditions that increase blood LDH levels include heart failure, heart attack, meningitis, and HIV [2].

Cancer cells can also use LDH to increase their own energy production, which can accelerate their rate of growth [3].

However, LDH is not very specific as a disease marker: it cannot generally be used to determine the exact cause of injury or specific kind of cancer [2, 4].

Lactate dehydrogenase (LDH) is an enzyme that plays an important role in energy production. Elevated levels of LDH in the blood may indicate tissue damage or cancer.

Lactate Dehydrogenase Test

Procedure

Your doctor may order an LDH test in cases when they want to check for tissue damage, like after a suspected heart attack. LDH may also be checked after a cancer diagnosis or if you show any signs of an infection to evaluate the severity of the illness [5].

A blood sample is required for the test. In special cases like meningitis or Kawasaki disease, samples may need to be taken from the spinal fluid or urine [6, 7].

Results are reported in units per liter (U/L) or international units per liter (IU/L), where a unit is an arbitrary amount that scientists have made the standard. This value reflects the amount of LDH that has been released into the bloodstream from damaged tissues.

If your LDH results are high, your doctor may also order an LDH isoenzymes test. This test is similar to a normal LDH test but it provides more precise information on the relative quantities of individual isoenzymes [8].

Your doctor may order an LDH test to evaluate tissue damage, an infection, or cancer progression.

Isoenzymes

There are actually five distinct types of lactate dehydrogenase, which are called LDH isoenzymes. Each isoenzyme has a slightly different structure, but they all work in a similar way [9].

The different isoenzymes are also concentrated in different areas of the body, although there is overlap. Isoenzymes and their areas of high concentration include [10]:

An increase in one type of isoenzyme may indicate an injury in the corresponding area; if you have increased LDH-3, your doctor will probably take a closer look at your lungs. Increases in several isoenzymes may signify severe illness, infection, or cancer [5].

Ratios comparing one isoenzyme to another are sometimes more helpful than a single isoenzyme. For example, an LDH-1:LDH-2 ratio may provide better diagnostic information about heart injury than LDH-1 alone [11].

There are 5 distinct types of LDH, which are called isoenzymes. Elevations in specific isoenzymes may indicate injuries in certain areas in the body.

CPK Test

Creatine phosphokinase (CPK), also known as creatine kinase (CK), is very similar to LDH. Both are enzymes found throughout the body that play a role in energy production [12].

A CPK test also serves a similar function: elevated levels of CPK may indicate tissue damage to the muscles, heart, and brain [12].

In the past, CPK and LDH tests were sometimes used together to evaluate muscle damage or help diagnose a heart attack, but they have been replaced with newer tests nowadays [13, 14].

Take a look at our CPK article for more information on this enzyme.

Normal Range of LDH

The range of LDH levels that are considered normal can vary depending on the lab testing the sample.

In general, normal levels for adults can range from 100 to 250 U/L [15, 16].

Children and infants typically have higher LDH levels. Normal ranges depend on the age of the child: newborns can have LDH values over 1,000 U/L, and this level tends to gradually decline until adulthood [17].

High Lactate Dehydrogenase Levels

The number of conditions that are known to elevate LDH levels is large and ever increasing. However, the effects of high LDH in many of these conditions is not fully understood.

Causes

1) Cancer

Many different types of cancer can cause elevations in LDH levels, including:

  • Gastric cancer [18]
  • Prostate cancer [19]
  • Lung cancer [20]
  • Testicular cancer [21]
  • Non-Hodgkin’s lymphoma [22]
  • Oral cancer [23]
  • Renal cell carcinoma [24]
  • Melanoma [25]

In most of these cancers, LDH levels can help predict how well a patient will do. A large study of 76 studies including over 22,800 cancer patients found that high LDH levels are strongly associated with lower survival rates in over 10 kinds of cancer [18].

According to another study, LDH levels above 1000 IU/L may indicate that a cancer is likely to be terminal. About half of patients with LDH levels this high did not survive past 2 months after starting cancer treatment [26].

But that’s not all: LDH has quite a unique relationship with cancer. Cancer cells prefer to use a process called glycolysis as an energy source, which takes place without oxygen. This process uses glucose as energy, turning it into pyruvate and lactate. LDH is required for this reaction to occur [27].

This means that LDH promotes the growth and spread of cancer cells, especially at high concentrations [27, 3].

On the bright side, this also means that LDH is a potential target for cancer treatment. Ongoing research is looking at anticancer drugs that can block LDH [3, 27, 1].

Many different types of cancer can elevate LDH levels. High LDH levels in cancer patients are associated with lower survival rates.

2) Heart Conditions

Conditions that cause damage or reduce oxygen flow to the heart can elevate LDH.

In the past, LDH was used as a lab marker to determine if someone had experienced a heart attack. Information about isoenzymes can be particularly helpful [28].

LDH-2 levels in the body are normally greater than LDH-1. After a heart attack, LDH-1 starts to outnumber LDH-2, a process called LDH flip.” This change in isoenzyme ratios can help diagnose a heart attack [11, 29].

However, LDH fell out of favor once better lab markers (like troponin) were discovered for heart attacks [28].

Idiopathic pulmonary arterial hypertension (IPAH) is a rare heart condition that increases LDH. In one study of 173 people with IPAH, researchers found that LDH levels are linked to risk of death [30].

For example, IPAH patients with LDH levels above 250 IU/L have a survival rate of only about 30%. Compare this to patients with levels below 250 IU/L, who have a survival rate of about 83% [30].

Heart conditions, like a heart attack or IPAH, can increase LDH levels in the blood.

3) Meningitis

Meningitis occurs when the protective tissues that surround the brain and spinal cord become inflamed. It is typically caused by an infection, but other factors can lead to meningitis, such as cancer and certain medications [31, 32].

Meningitis patients often have high LDH. Several studies revealed that higher LDH levels are associated with a worse prognosis [33].

For instance, one study that investigated cancer-related meningitis in 119 patients found that high LDH levels are linked to lower rates of survival [6].

Studies examining meningitis caused by infection produced similar results [34, 35].

Testing isoenzymes of LDH may also be useful in identifying the cause of each case of meningitis. A study of 157 children analyzed LDH isoenzymes in various forms of meningitis. They found that bacterial meningitis had uniquely low LDH-2 levels in spite of an increase in total LDH [36].

On the other hand, meningitis not caused by bacteria has relatively high LDH-3 levels. All types of meningitis have high levels of LDH-1, LDH-4, and LDH-5 [36].

People with meningitis often have elevated LDH. Higher levels of LDH are associated with lower rates of survival.

4) Infections

A number of different infections (including bacterial, viral, and fungal infections) can increase LDH. These include:

  • HIV [37]
  • Pneumocystis pneumonia [38, 39, 40, 41]
  • Infectious mononucleosis [42, 43]
  • Histoplasmosis [44]
  • Bacterial meningitis [45, 36]

Similar to other conditions, high LDH levels may indicate a poor prognosis.

One study investigated 84 people with Pneumocystis pneumonia, a form of the disease caused by a yeast-like fungus. Researchers found that most survivors have LDH levels that trend down over time, while 75% of individuals with increasing LDH levels did not survive [38].

Higher LDH levels are also associated with lower CD4+ counts in HIV patients, which can make them more susceptible to other infections [46, 39].

5) Anemia

People with anemia don’t have enough healthy red blood cells, which reduces oxygen supply to all their tissues [47].

LDH may help differentiate between various kinds of anemia and monitor disease progression [47].

For example, LDH levels (primarily isoenzymes 1 and 2) rise in hemolytic anemia, a type of anemia caused by an abnormal breakdown of red blood cells [47].

Other forms of hemolytic anemia affect LDH differently. Hemolytic anemia caused by birth defects only slightly raises LDH, while conditions caused by artificial heart valves can increase LDH levels by five times or more [47].

Megaloblastic anemia, wherein certain blood cells become enlarged, causes LDH levels to skyrocket to 3000 IU/L or more. It is also associated with higher ratios of LDH-1 to LDH-2, which helps distinguish it from other forms of anemia [48].

If you have anemia, LDH is useful for monitoring your response to treatment. Your levels will fall as your healthy red blood cells increase [47].

Different types of anemia can cause varying elevations in LDH.

6) Liver Failure

In acute liver failure, people suddenly and rapidly lose liver function. This form of liver failure massively increases LDH, according to a study of seven patients. In contrast, other liver disorders (like hepatitis and cirrhosis) only slightly raise LDH [49, 50].

Blocking LDH might turn out to be a treatment for acute liver failure in the future. Based on early mice studies, LDH-blocking drugs can reduce liver damage and improve survival [51].

7) Aortic Disorders

Acute aortic syndrome (AAS) refers to a group of disorders that all have one thing in common: damage to the inner layer of the aorta – the largest artery that goes from the heart [52].

This syndrome also increases LDH levels, according to a study of 999 emergency room patients whose LDH levels were about 424 U/L [53].

High levels of LDH in AAS are also linked to worse survival rates. For LDH values of 450 U/L or more, the risk of death is 32.6%. On the other hand, for LDH values below 450 U/L, the risk of death is 16.8% [53].

8) Brain Disorders

Certain brain disorders and injuries may increase LDH. In a study of 110 people who experienced a head injury, higher LDH levels were associated with more severe brain damage and a worse prognosis [54].

Research shows that several rare brain disorders may cause dramatic elevations in LDH.

If you had a brain injury, look into ways to “regrow” your brain. In theory, your LDH should normalize as your brain tissue regenerates.

One example is in posterior reversible encephalopathy syndrome (PRES), which causes headaches, seizures, altered mental states, and inflammation. One study found that patients with this condition experience an average increase of 115 IU/L above baseline in their LDH levels [55, 56].

Another example is in hypoxic-ischemic encephalopathy (HIE), a rare condition whereby a newborn infant’s brain does not receive enough oxygen. Newborns with this condition can have LDH levels over 3400 IU/L, based on one study of 30 infants [57].

Head injuries and several rare brain disorders can significantly increase LDH.

9) Muscle Damage

Conditions that cause muscle injury, including exercise-induced muscle damage, can increase LDH.

A small study of 12 men found that aerobic exercise and strength training both cause spikes in LDH, although strength training appears to trigger a greater increase [58].

Muscular dystrophy is a group of diseases that cause muscle weakness and breakdown. Out of five types of muscular dystrophy, three greatly increase LDH. The largest rise was in Duchenne muscular dystrophy, which increased LDH levels to four times the normal value [59].

A similar condition called rhabdomyolysis also causes rapid muscle breakdown. In this condition, dying muscle cells release their contents into the blood, including significant amounts of LDH [60].

Intense exercise and diseases that cause muscle damage may elevate LDH levels in the blood.

10) Tobacco Use

Cigarette smokers have significantly higher LDH levels compared to non-smokers, according to a study of 60 people [61].

It’s not just cigarettes, either. A different study found that people who use chewing tobacco have LDH levels over 400 U/L, on average. This result suggests that tobacco itself, rather than smoke, is the culprit behind this LDH rise [62].

11) Fluoridated Water

There is some evidence that the fluoride level in drinking water can influence LDH. According to a study of 210 children, fluoride in water increases LDH in a dose-dependent manner: as fluoride concentrations rise, so does LDH [63].

Negative Health Effects

Many illnesses are associated with high LDH levels. But LDH itself typically does not cause problems; rather, its presence exposes an underlying disease [2].

However, cancer is one case in which LDH does have a direct negative impact on health. Cancer cells use LDH for their energy production, allowing them to grow and spread uncontrolled [27, 3].

Some studies suggest that increased levels of LDH may promote inflammation, leading to even more tissue damage [51, 64].

This has led researchers to consider LDH inhibitors as a possible treatment for a variety of conditions, including cancer, liver failure, and epilepsy [27, 51, 65, 66].

LDH typically does not have a direct negative impact on health, except in cancer where it promotes the growth of cancer cells.

Ways to Decrease LDH

Talk to your doctor if your LDH levels are greater than normal. High LDH can be a sign of serious illness.

Several supplements may help keep LDH levels in check, such as:

Exercise and water high in fluoride may increase LDH levels; thus, avoiding too much of either may also help [73, 63].

Low Lactate Dehydrogenase Levels

Causes

LDH levels very rarely drop too low. The only evidence available is from case reports of LDH deficiency, a very rare genetic disorder in which the body cannot properly make the LDH enzyme [74, 75].

Effects

LDH deficiency can lead to fatigue, muscle pain, and muscle breakdown. If enough muscle tissue is broken down, the urine can become red or brown due to myoglobin, the protein that gives muscle its distinct red color [74].

Deficiencies can also lead to skin lesions similar to psoriasis [76].

However, in some forms of LDH deficiency, patients experience few symptoms or even no symptoms at all [75, 77].

Irregular Levels?

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Takeaway

Lactate dehydrogenase (LDH) is an enzyme involved in energy production that increases after tissue damage. 

Many illnesses can raise LDH, including cancer, heart attacks, and infections. High levels are your body’s alarm bell: they indicate something is not right. However, they won’t tell you much about the precise cause. Your doctor will order additional to determine what is wrong.

Low levels of LDH are very rare and are primarily caused by rare genetic disorders.

About the Author

Mathew Eng, PharmD

PharmD

Mathew received his PharmD from the University of Hawaii and an undergraduate degree in Biology from the University of Washington.

Mathew is a licensed pharmacist with clinical experience in oncology, infectious disease, and diabetes management. He has a passion for personalized patient care and believes that education is essential to living a healthy life. His goal is to motivate individuals to find ways to manage their chronic conditions.

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