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Optimal Liver Enzymes: Evidence Based Optimal Ranges for AST & ALT

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Published:
Oct 15, 2024
Editor:
Julija Rabcuka
24
min read
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Liver enzymes like ALT (Alanine Aminotransferase) and AST (Aspartate Aminotransferase) are not just markers of liver function—they provide key insights into overall metabolic and cardiovascular health. ALT, often referred to as the "liver enzyme," is predominantly concentrated in the liver, while AST has broader implications, with activity in the heart, muscles, and kidneys as well. Elevated levels can signify underlying issues not only in the liver but also in muscles and the heart. Elevated levels can signal liver damage, but even "normal" ranges may overlook early signs of liver damage, cardiovascular risks, and metabolic dysfunction.

At Superpower, we base our recommendations on the latest scientific research to define the optimal ranges for ALT and AST. Our evidence-driven approach focuses on proactive health management, addressing suboptimal enzyme levels early to support liver function and overall metabolic health.

Key Points

  • ALT & AST's Dual Role: ALT and AST are indicators of liver health but, also provide insight into broader metabolic and cardiovascular function.
  • "Normal" is Too Broad: Conventional ranges often miss early-stage liver and metabolic issues allowing for serious chronic disease to develop.
  • Conventional is NOT Optimal: Research shows that tighter ranges are better predictors of liver health and metabolic function.
    • Conventional Range for ALT: ~7-56 U/L
    • Conventional Range for AST: ~10-40 U/L
    • Optimal Range for ALT: 10-20 U/L
    • Optimal Range for AST: 10-20 U/L

What Does Your Liver Do?

The liver plays a central role in detoxification, acting as the body’s main filter for breaking down harmful substances like alcohol and processing blood from the stomach and intestines [1, 2]. It performs over 500 essential functions, including converting excess sugar into glycogen which the body can store for future energy [3]. The liver also metabolizes nutrients—proteins, fats, and carbohydrates—and manages fat production and breakdown, either storing it or converting it into energy as needed [1 - 3].

However, when excess fat builds up in the liver, it can lead to a condition known as fatty liver—an increasingly common issue that can disrupt many of the liver's vital functions. If not addressed, fatty liver can lead to inflammation and scarring, and in severe cases even progress to liver cancer [4 - 6].

What is “Fatty Liver”?

Fatty liver, or non-alcoholic fatty liver disease (NAFLD), occurs when 5-10% of the liver’s weight is made up of fat [7]. NAFLD has two forms: non-alcoholic fatty liver (NAFL), which often progresses without symptoms, and non-alcoholic steatohepatitis (NASH), which involves inflammation that can lead to scarring and increases the risk of liver cancer. NASH is also referred to as metabolic dysfunction-associated steatohepatitis (MASH or MASLD).

Historically, fatty liver was associated with heavy alcohol use, but it now affects around 25% of people worldwide, including ~10% of children, reaching to ~40% in children who are obese [8 - 10]. It is especially common among those with Type 2 diabetes (56%) and obesity (60-90%), but can also develop in people with insulin resistance, metabolic syndrome, or abnormal levels of blood lipids like triglycerides and cholesterol [7, 11].

The accumulation of fat in the liver isn't just a liver issue—it can trigger serious damage to other vital organs, including the heart.

What is ALT and AST?

Two key enzymes that help monitor the health of your liver are ALT (Alanine Aminotransferase) and AST (Aspartate Aminotransferase). Both enzymes play crucial roles in amino acid metabolism and are released into the bloodstream when liver cells are damaged. Elevated levels of these enzymes in blood tests can be an early sign of liver stress or injury.

ALT (Alanine Aminotransferase)

ALT is primarily concentrated in the liver, where it plays a crucial role in the conversion of alanine, an amino acid, into pyruvate [12]. Pyruvate is a key molecule that enters the energy-producing cycle (the Krebs cycle) to fuel liver cells. This reaction is essential for the liver’s energy metabolism, as it helps break down proteins so the liver can use them as an energy source or for producing other vital compounds.

When the liver is healthy, ALT levels in the blood are low. However, when liver cells are damaged, inflamed, or die, ALT is released into the bloodstream, causing elevated levels [13, 14]. Because ALT is mostly concentrated in the liver, it is considered the most specific biomarker for detecting liver damage. Elevated ALT levels are often the earliest sign of chronic liver conditions, even before other symptoms appear [12, 14].

AST (Aspartate Aminotransferase)

AST (Aspartate Aminotransferase) is another enzyme that helps in amino acid metabolism. Unlike ALT, which is mostly found in the liver, AST is present in several organs, including the liver, heart, muscles, kidneys, and brain [15, 16]. This broader presence means that AST plays a role in the normal function of these tissues.

In a healthy body, AST levels in the blood remain relatively low. However, when tissues that contain AST—especially the liver—are damaged or stressed, this enzyme is released into the bloodstream, causing its levels to rise [17]. Because AST is found in multiple organs, elevated levels can signal damage in various tissues, not just the liver. For instance, heart attacks (myocardial infarctions) or muscle injuries can cause a rise in AST without significantly affecting ALT levels. This makes AST a versatile biomarker, not only for assessing liver health but also for detecting potential problems in the heart and muscles.

ALT and AST levels often rise together in response to liver damage, but the ratio between them can provide important clues about the cause and extent of liver injury. When both enzymes are elevated, it usually signals liver inflammation or damage, but the ALT-to-AST ratio can help differentiate the underlying issue [18, 19].

Why Should You Care About AST and ALT?

AST and ALT are not just markers for liver damage—they provide key insights into metabolic and cardiovascular health. Elevated levels can be early signs of issues like non-alcoholic fatty liver disease (NAFLD), insulin resistance, and even cardiovascular risk. These enzymes are often elevated when there is inflammation or oxidative stress, two major drivers behind the development of chronic diseases [18, 19].

Liver Damage

Elevated ALT and AST levels are often the first signs of liver damage. This damage can be caused by a variety of factors such as fatty liver disease, alcohol consumption, hepatitis, or even medications. Conditions like non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH/MASH) are becoming increasingly common and can progress silently for years, often without symptoms until significant liver damage occurs. Elevated ALT is particularly associated with liver injury, while elevated AST might also reflect damage to other tissues like the heart and muscles [12 - 19].

Metabolic Dysfunction

Recent studies have also linked elevated ALT and AST levels to the development of metabolic syndrome, a cluster of conditions that raise your risk for heart disease, stroke, and type 2 diabetes [7]. Elevated ALT is particularly associated with fatty liver disease, which can lead to insulin resistance and disrupted sugar metabolism. Even modest elevations in ALT are correlated with increased risks of metabolic disorders, and elevated levels can be an early indicator of type 2 diabetes, often before any symptoms appear [20].

Heart Health

There is also evidence suggesting that elevated ALT and AST might be early markers of cardiovascular disease [21 - 24]. While ALT is more specific to the liver, both enzymes, when elevated, have been linked to an increased risk of heart disease and stroke. Elevated AST, in particular, may indicate cardiac stress or injury due to its presence in heart tissue.

Cancer Risk

Chronically elevated ALT levels may also signal an increased risk for liver cancer and other malignancies [25 - 29] . Prolonged liver inflammation and damage can eventually lead to cirrhosis or liver cancer, especially in individuals with ongoing liver conditions like NAFLD or hepatitis.

Lifespan Studies

Finally, research shows that elevated ALT and AST levels, even within the "normal" range, are associated with a higher risk of death from all causes [25, 30 - 33]. Elevated liver enzymes may reflect underlying inflammation or oxidative stress, which are key drivers of aging and chronic disease development [34, 35]. Persistent elevation of ALT has been linked to a reduced lifespan in individuals with chronic liver conditions, metabolic problems, and cancer risk.

Conventional Reference Range for AST and ALT

The conventional reference range for ALT and AST can vary slightly between laboratories, but it's typically considered:

  • Normal for men: ~ 10 to 56 U/L
  • Normal for women: ~ 7 to 46 U/L
Some labs may use a unified range of 0 - ~ 50 U/L for both sexes.

Traditional reference ranges for AST and ALT are typically designed to detect overt liver disease, but they often miss subtler, early-stage issues like metabolic dysfunction. Even liver enzyme levels within the "normal" range can be associated with increased risks of metabolic syndrome, cardiovascular disease, and liver disease. While elevated levels usually indicate liver damage, research suggests that even the lower end of the "normal" range may still pose health risks.

Superpower Optimal Range for AST and ALT

At Superpower, we recommend a more stringent optimal range for both ALT and AST:

  • Superpower Optimal Range for ALT: <20 U/L for both men and women
  • Superpower Optimal Range for AST: <20 U/L for both men and women

Our recommended ranges are based on research linking lower enzyme levels to improved liver health, metabolic function, and increased longevity. Studies show that these ranges reduce the risk of fatty liver disease, insulin resistance, and liver inflammation, while also enhancing metabolic health and lowering cardiovascular risk.

Knowledge Gap: Traditional biomarkers of liver injury often correlate with biomarkers of muscle damage therefore, intense exercise can cause your liver function tests to come up elevated [36, 37]. Traditional diagnostic pathways rarely account other possible causes of elevated liver biomarkers, especially in young and active adults.

‍

For a more comprehensive assessment of liver function, we recommend also evaluating GGT (Gamma-Glutamyl Transferase). Elevated GGT levels can signal biliary disease, alcohol-related liver damage, and oxidative stress.
Additionally, markers like bilirubin (which reflects the liver’s ability to break down red blood cells) and alkaline phosphatase (ALP) (which helps assess bile duct function) can help identify issues that may not be apparent through ALT and AST levels alone.

Why Is The Conventional Range For ALT and AST Problematic?

Conventional reference ranges for ALT and AST often fail to detect early liver damage and metabolic dysfunction. These ranges are designed to identify obvious liver disease, but they miss subtler, early-stage problems that can lead to chronic conditions. By the time ALT or AST levels reach the upper limit of "normal," significant liver stress or damage may already be present, increasing the risk of conditions like non-alcoholic fatty liver disease (NAFLD), which often progresses silently.

The conventional ranges are too broad and lack sensitivity to catch early signs of metabolic dysfunction or NAFLD, where even slight elevations can reflect ongoing liver stress or inflammation. In fact, the upper limit of "normal" often coincides with the early stages of metabolic syndrome, poor sugar metabolism, and insulin resistance, allowing these conditions to progress unnoticed until they become more serious. This delay in detection can lead to chronic disease or more severe cardiovascular complications.

ALT levels that remain in the upper end of the normal range are strongly associated with an increased risk of metabolic syndrome, particularly in women [38]. Another study found that elevated ALT and AST levels, even within the normal range, predict the development of metabolic syndrome, suggesting that current ranges are not sensitive enough to detect early liver dysfunction related to NAFLD [39].

Research also shows that subtle increases in AST and ALT within normal ranges are tied to metabolic risk factors such as waist circumference, triglycerides, and fasting blood sugar. This implies that even mild elevations in these enzymes may indicate underlying liver and metabolic dysfunction [40].

Furthermore, conventional ranges are based on population averages rather than optimal health outcomes. In today’s environment of over-nutrition and sedentary lifestyles, "average" enzyme levels do not reflect good health. Evidence shows that current ALT and AST ranges are skewed due to the high prevalence of fatty liver disease. One study suggests that the upper limit of 40 U/L for ALT is too high, potentially including individuals with undetected NAFLD. Proposed cutoffs of 30 U/L for men and 19 U/L for women have been recommended to better identify early-stage liver disease [41].

A study found that nearly 54% of individuals with NAFLD fell within the conventional ALT reference range, indicating that the current ranges are skewed by the widespread presence of NAFLD in the population [42]. Additionally, research on obese women shows that adopting lower ALT guidelines would better identify patients with NAFLD or scarring of the liver (called fibrosis), highlighting the inadequacy of current ranges in detecting early liver disease [43].

Supporting Evidence From Research Studies

A growing body of research strongly supports the case for maintaining lower ALT and AST levels to improve liver health, metabolic function, and overall longevity.

Liver Health and NAFLD

The World Gastroenterology Organisation (WGO) guidelines suggest that in morbid obesity, diabetes and ALT/AST levels above 27 IU/L are associated with high risk of progression to NASH/MASH. Studies have proposed a new ALT upper limits of normal for healthy males and females to be 30 U/L and 19 U/L, respectively, to be diagnostically useful in NAFLD [44]. Subsequent studies found that NAFLD was associated with normal ALT values and that employing the “revised” cut-offs results in a significant increase in biopsy-proven NAFLD with the application of the new standard [45 - 47].

Studies have shown that ALT levels below 19 U/L in men and 30 U/L in women are associated with a significantly reduced risk of NAFLD [45, 47, 48]. Additionally, studies suggest that ALT levels under 20 U/L are linked to a slower progression of NAFLD, further reinforcing the need for tighter control of ALT levels to protect liver function [49, 50].

Research has also demonstrated a clear connection between AST and NAFLD [49, 51, 52]. The risk of NAFLD increased significantly when AST levels exceeded 20 U/L, even within the normal range, emphasizing the importance of maintaining lower AST levels to prevent liver disease [52, 53]. Lower AST levels have been associated with a reduced risk of liver fibrosis. A study on chronic hepatitis B patients found that AST levels below 20 U/L were linked to a lower likelihood of developing significant liver fibrosis, even when other liver enzyme levels were within the normal range [54].

Metabolic Health

Lower ALT levels have also been tied to better metabolic health [55]. Higher ALT levels, even within the normal range strongly predict the likelihood of developing type 2 diabetes, regardless of body weight. The risk also increases as ALT levels go up [56].Individuals with ALT levels around 20 U/L had a reduced risk of developing type 2 diabetes, suggesting that keeping ALT in the lower range may play a role in preventing metabolic disorders linked to insulin resistance [57 - 59].

Similarly, studies show that individuals with AST levels at the upper end of the normal range (25-40 U/L) had a higher risk of developing metabolic syndrome when compared to those with AST levels below 20 U/L [60].

The risk for NAFLD increases with insulin resistance and other metabolic risk factors like obesity, high blood sugar, and abnormal cholesterol levels [61]. Studies that exclude people with these risk factors from reference populations have found that the upper limit of normal ALT is lower—around 30 IU/L for men and 19 IU/L for women [13, 44, 62].

Cardiovascular Health

Research results regarding ALT and AST levels and their association with cardiovascular risk are varied. While some studies suggest that lower ALT levels may correlate with a reduced risk of heart disease and death, the evidence is not consistent across all populations [23, 63, 64].

Both ALT and AST are often elevated in conditions such as metabolic syndrome, insulin resistance, and high blood pressure, which are key contributors to cardiovascular disease. Elevated levels can negatively impact heart health through various mechanisms, including increased oxidative stress, inflammation, insulin resistance, and metabolic dysregulation [64]. These processes contribute to the development of atherosclerosis and other heart diseases.

Inflammation

Inflammation is a key driver of many chronic diseases, and studies show that elevated liver enzymes within the normal range are linked to higher levels of inflammatory markers. ALT is positively associated with markers like C-reactive protein and interleukin, even independent of metabolic syndrome and body mass index [64, 65]. Additionally, liver inflammation is closely tied to oxidative stress, which can further damage cells and contribute to the progression of chronic diseases. This combination of liver inflammation and oxidative stress may drive the low-grade inflammation that underpins many chronic conditions [66].

Cancer Risk

Elevated ALT levels have also been associated with an increased risk of liver cancer and other malignancies [25 - 29]. Maintaining ALT below 30 U/L for men and below 20 U/L for females was linked to a reduced risk of liver cancer [67]. The AST/ALT ratio can be used to evaluate overall health and predict long-term survival. In particular, a higher ratio is often seen before cancer develops and can even help predict the future risk of cancer [67].

Longevity and Overall Mortality

The relationship between ALT and AST levels and overall mortality is complex, with evidence suggesting a "U-shaped" association where both low and high levels are linked to increased mortality risk.

Elevated ALT and AST levels are associated with chronic conditions such as cardiovascular disease, liver disease, and metabolic syndrome, all of which reduce life expectancy [68]. ALT levels above 29 U/L have been linked to higher mortality in patients with metabolic disorders, while AST levels above 40 U/L are associated with a 10.2-year reduction in life expectancy [69]. Even after adjusting for confounders, an elevated AST/ALT ratio remains a significant predictor of mortality [70].

Given these risks, some researchers suggest lowering the upper cut-off for ALT to ~22 U/L, as higher levels are associated with factors like higher BMI, alcohol intake, and elevated fat profile in the blood [71]. A review of NHANES data recommends a cut-off of 29 U/L for men and 22 U/L for women to better identify those at risk for liver disease, including hepatitis C [72].

Interestingly, some studies found that extremely low ALT and AST levels are linked to frailty, muscle wasting, and metabolic decline, which can occur in the later stages of chronic diseases or aging [23, 24, 73]. ALT levels below 20 U/L have been associated with higher mortality in hospitalized patients, likely due to these underlying health issues [74].

The Key Takeaway

ALT and AST are common indicators of liver function, but they also provide valuable insights into metabolic, cardiovascular, and overall health. Conventional ranges for these enzymes are often too broad, potentially missing the early signs of liver damage and metabolic dysfunction. Emerging research suggests that a more optimal range for ALT and AST is 10–20 U/L, which not only supports liver function but also reduces inflammation and lowers the risk of metabolic and cardiovascular diseases.

At Superpower, we base our reference ranges on the latest clinical research and systems physiology, ensuring they reflect cutting-edge science. By focusing on more precise ALT and AST ranges (<20 U/L), we aim to optimize liver function, reduce inflammation, and improve metabolic health. Keeping these enzymes within the optimal range helps prevent liver diseases and metabolic dysfunction, promoting long-term well-being, healthspan, and longevity.

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Longevity Markers
Inflammation
Electrolytes
Heavy Metals
Hormone Health
Blood
Heavy Metals & Electrolytes
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Nutrients
Male Health
Female Health
Immune Regulation
Thyroid Health
Heart Health
Gut Health
Metabolic Health
Nutrition
Longevity Markers
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Inflammation
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Electrolytes
/
Heavy Metals
/
Hormone Health
/
Blood
/
Heavy Metals & Electrolytes
/
Kidney Health
/
Liver Health
/
Nutrients
/
Male Health
/
Female Health
/
Immune Regulation
/
Thyroid Health
/
Heart Health
/
Gut Health
/
Metabolic Health
/
Nutrition
/
Longevity Markers
Inflammation
Electrolytes
Heavy Metals
Hormone Health
Blood
Heavy Metals & Electrolytes
Kidney Health
Liver Health
Nutrients
Male Health
Female Health
Immune Regulation
Thyroid Health
Heart Health
Gut Health
Metabolic Health
Nutrition
Longevity Markers
/
Inflammation
/
Electrolytes
/
Heavy Metals
/
Hormone Health
/
Blood
/
Heavy Metals & Electrolytes
/
Kidney Health
/
Liver Health
/
Nutrients
/
Male Health
/
Female Health
/
Immune Regulation
/
Thyroid Health
/
Heart Health
/
Gut Health
/
Metabolic Health
/
Nutrition
/