What Does it Mean When Your ALT is High?
Healthy liver cells store most of your ALT, but small amounts are also found in the muscles and blood. When liver cells are damaged due to illness, injury, or medication, they release ALT, increasing its blood levels .
Therefore, ALT blood levels are a marker of liver health: low levels typically indicate a healthy liver, while high levels suggest liver damage .
What is Considered a High Level?
ALT is measured in units per liter of blood or U/L. The most recent comprehensive review concluded that the upper normal limit for ALT should be:
- 31 U/L for women
- 42 U/L for men
Until recently, however, 10 to 40 U/L was considered as the normal range for both genders .
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Causes & Health Effects of High ALT Levels
1) Non-Alcoholic Fatty Liver Disease
Non-Alcoholic fatty liver disease is characterized by liver inflammation, fat buildup, and in extreme cases, severe, irreversible damage. It affects approximately 35% of the US population and often occurs alongside diabetes and obesity .
High ALT levels may also predict non-alcoholic fatty liver disease. In a study of 72 overweight adolescents, 32% of those with high ALT also had abnormally high levels of liver fat .
In a study of 390 people with a non-alcoholic fatty liver disease, 43% had normal ALT levels. High ALT levels weren’t linked with inflammation either. In a study of 101 patients, those with normal and high ALT levels had similar non-alcoholic fatty liver disease severity and risk of developing further complications [11, 12].
2) Alcohol Consumption
Excessive alcohol consumption is the most common cause of liver disease in the Western Hemisphere .
In multiple studies from around the world (1.1 million Korean participants, 46k English men, 24k Americans, 6k Koreans, and 125 Italians), ALT levels increased with daily alcohol consumption [14, 15, 16, 17, 18, 19].
Alcohol breakdown takes a significant toll on liver health by causing free radical damage and increasing levels of inflammatory markers (TNF-α). Long term, excessive alcohol consumption leads to liver cell death, releasing ALT from the liver into the bloodstream [20, 21, 13].
But the relationship between ALT and alcohol drinking is more complicated than that. In a study of 13,580 adults, drinking alcohol increased ALT levels more in overweight people who already had elevated ALT than it did in those with normal weight [22, 23, 24].
In a study of 6,095 patients with hepatitis, drinking alcohol further increased ALT levels in people with hepatitis C but not hepatitis B .
Furthermore, alcoholics with higher ALT levels were more likely to experience severe alcohol withdrawal in a meta-analysis of 15 studies .
However, in a study of 273 Japanese participants, even those who drank up to 81 g of alcohol per day (about 6 drinks) had only slightly increased ALT. In 125 Italian participants, “moderate” alcohol consumption (≤ 4 drinks per day) did not increase ALT levels [25, 19].
Limited drinking may not increase ALT levels in normal-weight individuals due to its ability to improve insulin sensitivity, which seems to reduce ALT, according to trials on almost 14,000 people [22, 26].
In a two-year study of 182 patients, 12% of people had very high ALT (greater than 1,000 U/l) due to a hepatitis infection .
In one case study, a 4-year-old girl chronically-elevated ALT levels from autoimmune hepatitis, even though she experienced no other symptoms .
However, in a study of 280 patients with hepatitis C who were symptom-free, 17% had normal levels of ALT and 45% had mildly elevated ALT levels (below 80 U/L) .
However, in a meta-analysis of 9 studies with 830 patients with hepatitis B, about a fifth of the patients who had normal ALT levels had severe liver scarring (liver fibrosis) .
In another meta-analysis of 8 studies with 683 patients with hepatitis B, nearly half of the patients with relatively low ALT levels had advanced liver damage .
In a meta-analysis of 17 studies involving over 60k participants, the risk of developing type 2 diabetes increased as ALT level increased .
In a 5-year study with 724 participants, elevated ALT levels predicted future development of diabetes in cases where other factors did not (including BMI, fasting blood sugar, and family history) .
ALT levels were also positively associated with prediabetes, the intermediate step between high blood sugar and diabetes .
Those with high ALT levels also showed signs of diabetes–such as high fasting blood sugar, increased insulin resistance, and impaired glucose tolerance–in several studies of over 18,000 adults and adolescents [27, 39, 40].
In a study of nearly 17,000 adults, those with higher ALT levels were more likely to die from diabetic complications .
High ALT levels were common in a study of 115 children with type 2 diabetes. These children could be at a greater risk of developing non-alcoholic liver disease .
In a study of 56 patients with type 1 diabetes, those with high ALT levels were more likely to have high BMI, high fasting blood sugar, and increased levels of HbA1c. This marker indicates if blood sugar had been high over a long period of time .
Stomach fat is more dangerous than general obesity and often accompanies conditions such as diabetes and liver disease. Waist circumference and stomach fat more accurately predicted ALT than the standard measurement of body mass index (BMI), as seen in multiple studies of over 17,000 adults, adolescents, and children [47, 48, 49, 50, 51, 52, 53, 54].
In a study of 290 obese patients, insulin resistance was associated with high ALT .
6) Metabolic Syndrome
Metabolic syndrome describes a number of interconnected symptoms that increase the risk of heart disease, diabetes, and the risk of dying in general. These symptoms include high blood pressure, high cholesterol, chronic inflammation, stomach fat, and insulin resistance .
In a meta-analysis of 5 studies with 29,815 participants, a risk of developing metabolic syndrome increased by 14% for every additional 5 U/L of ALT in the blood .
In another study with 28,456 participants, people in the top quarter of ALT levels were 82% more likely to suffer from metabolic syndrome than those in the bottom quarter .
In 2 studies with 5,586 adolescent and 1,740 adult participants, high ALT levels were significantly associated with increased C-reactive protein levels (often high in people with metabolic syndrome). Liver inflammation may contribute to chronic inflammation in patients with metabolic syndrome [49, 59, 60, 61, 62, 63].
7) Iron Overload
In a study with 3,455 participants, high ALT levels were associated with increased levels of the iron-regulating hormone hepcidin, indicating that the body could be trying to protect the liver from iron overload by releasing hepcidin .
In mice, increased iron in the blood caused inflammation, free-radical damage, and a buildup of scar tissue in the liver, resulting in high ALT levels .
In a study of 100 patients with hemochromatosis, 65% had high levels of ALT .
Hemochromatosis causes iron overload by blocking the production of the iron-regulating hormone, hepcidin .
8) Muscle Disease or Injury
Since small amounts of ALT are stored in muscle cells, muscle injury and disease can also cause ALT to leak into the blood and raise its levels .
In a study of 620 patients with inflammatory muscle disease (polymyositis or dermatomyositis), 43% had high ALT levels .
Almost 88% of 232 patients with muscular dystrophy, an inherited disease where muscles weaken and waste away, had high levels of ALT in one study .
In a study with 16 patients with various muscle injuries, extreme exercise and seizures increased ALT levels .
In certain types of muscle disease, the severity of damage can be tracked by measuring ALT levels. In 189 patients in the ICU with rhabdomyolysis, a condition where muscles break down rapidly, those with ALT levels above 1000 U/L were 46.2% more likely to die than patients with lower ALT levels [76, 76].
ALT levels also mirrored those of creatine kinase, another marker of muscle damage, in a study of 85 patients with muscular disease (idiopathic inflammatory myopathy) .
In a meta-analysis of 29 studies with 1.23 million participants, high ALT levels moderately increased the likelihood of stroke .
In a study with 279,982 Asian participants, men with elevated levels of ALT were 74% more likely to suffer a stroke than men with low ALT, though this association was less prominent in women (60%) .
10) High Levels of Cholesterol and Other Blood Fats
ALT, LDL cholesterol, and triglycerides (the main type of fat found in the body) are often high together. This may be due to the effects of insulin resistance and fatty liver disease, suggesting that high cholesterol and ALT are caused by an underlying issue [45, 16, 80].
11) High Blood Pressure
Out of 69 active NFL players, elevated ALT was more common in linemen, who also tended to have high blood pressure .
High blood pressure and ALT may be caused by other health problems. People with non-alcoholic liver disease, type 2 diabetes, and metabolic syndrome generally have both high blood pressure and high ALT levels (27,769 participants, 96 participants) [84, 85].
In a study where all 151 participants had a non-alcoholic liver disease, those with especially high ALT levels were more likely to have high blood pressure .
12) High Uric Acid
Another study with 11,898 participants found the same to be true only in women .
13) Antioxidant Deficiency
Specifically, the levels of carotenoids (alpha-carotene, beta-carotene, other carotenoids, beta-cryptoxanthin, lutein/zeaxanthin) and vitamin C were lower in patients with high ALT levels in the study with 13,605 participants .
In another study of 1,037 participants over 7 years, people with low levels of provitamin A (beta-carotene, beta-cryptoxanthin, and total carotenoids) were 70% more likely to develop elevated ALT than participants with high levels of these antioxidants .
- Improving insulin resistance
- Reducing the activation of genes that cause cell death
- Turning white blood cells into anti-inflammatory molecules (M1 macrophages)
- Blocking damage (from the release of free radicals from the breakdown of fats)
14) Bile Disease
In a study of 424 patients with inflamed gallbladders (cholecystitis), those without gallstones had moderately raised ALT levels (82.5 U/L), and those with gallstones had noticeably raised ALT levels (95 U/L) .
In case studies of 7 patients with gallstones, ALT levels were initially very high—greater than 1,000 U/L–in 5 cases. ALT levels decreased as soon as the gallstones were removed, bile flow restored, and liver damage normalized [98, 99].
Higher initial ALT levels in younger patients before gallstone removal predicted a quicker recovery .
Gallstones also cause pancreatitis by blocking the bile duct and forcing the bile back into the pancreas .
The ALT levels of patients with pancreas inflammation due to gallstones was 200 U/L on average, much higher than levels in patients in which the inflammation was caused by other factors (33 U/L), in a study of 543 patients .
In a study of 275 patients with pancreas inflammation, high ALT levels (greater than 150 U/L) accurately predicted 97% if the inflammation was due to gallstones .
However, in another study of 167 patients with pancreas inflammation, ALT levels could not predict gallstones. In a 9-year study of 239 patients who had their gallbladders removed to treat this condition, those who had normal ALT levels were more likely to develop pancreas inflammation again [103, 104].
15) Celiac Disease
In a study of 140 patients with chronically elevated ALT that was not explained by liver disease, diabetes, or alcohol intake, 8.5% turned out to have the undiagnosed celiac disease .
In 2 studies with over 300 adults with the untreated celiac disease, 42 to 47% had high ALT levels. After eating a strict gluten-free diet, ALT levels normalized in 95 to 100% of these individuals [107, 108].
However, in a study with almost 14k participants with celiac disease and 66k healthy controls, celiac patients were 2 to 6 times more likely to suffer from liver disease. This suggests that untolerated gluten might create long-term damage to the liver .
16) Not Enough Oxygen
A study of 182 patients with extremely high ALT levels over 2 years identified poor circulation as one common cause of extreme ALT elevation (greater than 1,000 U/L) .
In a study of 85 patients with liver disease, those with sleep apnea were more likely to have elevated ALT levels. In another study of 540 participants with sleep apnea, lower oxygen levels accurately predicted high ALT levels [111, 112].
The body can respond to the lack of oxygen by creating additional red blood cells to carry more oxygen. This raises hematocrit, a blood markerr that measures the percentage of red blood cells in the blood .
In a study of 1,242 healthy participants, hematocrit accounted for 3% of the variation in ALT level–less than BMI and gender, but more than blood pressure and cholesterol .
Hypoxia can lead to damage and inflammation, while also reducing the liver’s ability to regenerate by creating new blood vessels and connective tissue. This was tested in a rat model of sleep apnea: occasional hypoxia damaged the liver (by free radicals), which eventually became full-blown non-alcoholic fatty liver disease [115, 116, 117].
The liver disease itself can also reduce oxygen in liver cells, creating a positive feedback loop that quickly worsens liver health .
17) Viral Infection
In a meta-analysis of 11 studies of 2,086 dengue (a tropical virus carried by mosquitoes) patients, 52% of patients with dengue fever and 54% of patients with life-threatening dengue (hemorrhagic) fever had abnormally high ALT levels .
This is likely due to inflammation from the dengue virus that creates lesions on the liver, based on a study with 169 dengue patients .
In 41 patients with mononucleosis, ALT initially increased about 5-fold but returned to normal after 20 days .
High ALT may signal a strong infection. In a study of 353 dengue patients, those with very high ALT levels were more likely to spend more time in the hospital, experience kidney or liver failure, and die [121, 122, 123, 121].
18) Drug Overdose
In a study of 1,254 methamphetamine-dependent patients, those with severely high ALT (> 80 U/L) were 84% more likely to die, and those with moderately high ALT (> 40 U/L) were 59% more likely to die than those with normal ALT levels .
19) Choline Deficiency
Choline deficiency can cause liver cell death and fat accumulation in the liver, eventually leading to liver disease and possibly liver cancer .
Rats with choline deficiency had significantly higher ALT levels than those that ate a choline-supplemented diet .
However, research in humans is still underway. In a study of 15 patients receiving nutrition through an IV (parenteral nutrition), choline reduced ALT levels after 6 weeks. In a study of 60 men (with different MTHFR variants), choline supplements (550 mg per day) did not reduce ALT levels but did prevent ALT from rising [129, 130].
20) Pregnancy Complications
In a study of 430 pregnant women, those with unexplained high ALT–not caused by diabetes, liver disease, or alcohol consumption–were 82% more likely to develop pregnancy-induced diabetes, excluding obese mothers .
In a study of 323 pregnant women, those with high ALT during their first trimester were 80% more likely to have a larger than an average-sized baby (macrosomia) .
21) Cancer (in Asian Populations)
In a meta-analysis of 14 studies with 1.79 million participants, Asians with high ALT levels were 65% more likely to develop cancer than those with lower levels. No such link has been made in Europeans .
In a study of 782,632 Korean men, those with high ALT were 62% more likely to develop esophageal cancer and 60% more likely to die from it than men with low ALT levels .
22) Risk of Dying (in Asian Populations)
In a meta-analysis of 19 studies with 9.24 million participants, Asian participants in the top third for ALT levels were 43% more likely to die from any cause than those in the bottom third. However, this association was not seen in North America participants .
24) Maybe Heart Disease
Low ALT is typically associated with an increased likelihood of heart disease, but some researchers have found the opposite or no association at all .
According to a meta-analysis of 29 studies with 1.23 million participants, higher ALT levels were linked with heart disease in Asian populations, but the opposite was true in European and North American populations .
Liver diseases that raise ALT levels and risk of heart disease–such as non-alcoholic and alcoholic liver disease–often go undiagnosed in Asian populations, possibly explaining population differences [78, 139].
High ALT levels also increased the likelihood of an enlarged heart in a pilot study of 151 patients with non-alcoholic liver disease .
In another study of 610 patients, those with coronary heart disease had 230% more ALT in their blood than the healthy controls (independent of confounding factors such as alcohol consumption, high blood pressure, and elevated cholesterol) .
Want to Learn More?
This post is part of a series about ALT. Find out how to naturally lower your levels in the next part.
High ALT levels usually point to liver damage. The most common causes are non-alcoholic liver disease, excessive alcohol drinking, and viral hepatitis. Muscle-wasting diseases, iron overload, poor blood flow, nutrient deficiency, celiac disease, and other health problems can also raise ALT levels.