Episode #389: Your Liver Enzymes Are Elevated — But It Might Not Be Your Liver

Summary

A fit, healthy 39-year-old was nearly sent for a liver biopsy. The cause? Was it that he went to the gym before every blood draw or because his supplement was throwing his labs off?. Dr. Jordan Feigenbaum and Dr. Austin Baraki break down the blind spot that sends thousands of healthy athletes down an expensive, potentially unnecessary diagnostic rabbit hole every year.

🎧 Listen on Apple Podcasts: https://podcasts.apple.com/au/podcast/episode-389-your-liver-enzymes-are-elevated-but-it/id1199780143?i=1000754111837

Key Takeaways

• Asymmetry as a Feature: Human bodies are not naturally symmetrical. In many athletes—such as tennis players, pitchers, or rowers—asymmetry is a functional adaptation to the sport’s demands.
• The Pathological vs. The Normal: Acutely acquired asymmetries (post-surgery or trauma) require specific clinical attention. Long-standing or gradually acquired asymmetries are rarely the primary driver of pain.
• Saturated Fat & The Healthy User Bias: While fit individuals have a lower overall risk profile, elevated LDL and ApoB particles represent a “time-volume” exposure risk that should not be ignored based solely on lifestyle.
• The Lean Mass Hyper-Responder (LMHR): We analyze the bold claims surrounding the LMHR phenotype and discuss why mechanistic hypothesizing currently lacks the “hard human outcome receipts” to prove long-term safety.
• Body Fat Regulation: The Dual Intervention Point Model suggests the body defends a lower boundary (starvation) and an upper boundary (predation). In the modern environment, the “predation pressure” has vanished, leading to a genetic drift upward in body fat set points.

Episode Timestamps

• 00:01:09  Introducing the Case
• 00:03:44  How to Read a Liver Panel: ALT, AST, GGT, Alk Phos, Albumin Explained
• 00:10:50  What Is GGT and Why Does It Matter Clinically?
• 00:16:38  Why Exercise, Protein, and Creatine Aren’t on the Differential (Yet)
• 00:17:35  The Workup: Hepatitis Panels, Abdominal Ultrasound, and More
• 00:19:42  Second Set of Labs — The Mystery Deepens
• 00:25:25  Updated Differential: What’s Still on the List?
• 00:27:08  The Labs Normalize — A Critical Clue Appears
• 00:31:40  The Reveal: Exercise Was the Cause All Along
• 00:32:18  The Mechanism: How Exercise Elevates ‘Liver’ Enzymes
• 00:32:54  Point 1 — ALT & AST Are Not Exclusively Liver Enzymes
• 00:33:49  Point 2 — It’s Unavoidable: 100% of Lifters Are Affected
• 00:36:02  Point 3 — It Takes 10–12 Days to Normalize
• 00:37:00  Point 4 — It’s Mostly Harmless
• 00:38:27  56% of Physicians Miss This Diagnosis
• 00:38:48  Why Clinicians Overlook Exercise History
• 00:44:01  Point 5 — GGT as the Differentiator (And Its Limits)
• 00:46:42  Why Alkaline Phosphatase Also Rises Post-Workout
• 00:48:51  The Cost of Missing Lifestyle Context: Over- and Under-Diagnosis
• 00:53:29  What to Say to Your Doctor: 3 Patient Scripts
• 00:59:31  5 Key Takeaways
• 01:00:25  Final Advice from Dr. Baraki 

Clinical Pearls

References

• Case: https://pubmed.ncbi.nlm.nih.gov/37025214/
• https://pubmed.ncbi.nlm.nih.gov/29059178/ 
• https://pmc.ncbi.nlm.nih.gov/articles/PMC7438350/
• https://pubmed.ncbi.nlm.nih.gov/18557801/
• https://pubmed.ncbi.nlm.nih.gov/19209234/
• https://pubmed.ncbi.nlm.nih.gov/11476029/
• https://pmc.ncbi.nlm.nih.gov/articles/PMC11165564/
• https://pmc.ncbi.nlm.nih.gov/articles/PMC12460594/ 
• https://pmc.ncbi.nlm.nih.gov/articles/PMC2291230/
• https://pmc.ncbi.nlm.nih.gov/articles/PMC11319523/ 
• https://pmc.ncbi.nlm.nih.gov/articles/PMC3936967/
• https://pmc.ncbi.nlm.nih.gov/articles/PMC12188904/
• https://pmc.ncbi.nlm.nih.gov/articles/PMC7969109/
• https://pmc.ncbi.nlm.nih.gov/articles/PMC11498664/
• https://pmc.ncbi.nlm.nih.gov/articles/PMC3104191/

Transcript

Every year, thousands of healthy, active individuals are told their liver is failing based on a routine blood panel. The clinician sees the labs, the patient sees the panic in the doctor’s eyes, and the next few weeks are filled with expensive imaging, viral screenings, and the looming threat of a biopsy. 

We are taught that elevated transaminases, which are more correctly called- liver associated enzymes—mean liver pathology, and for the fitness enthusiast, this often leads to a recommendation to stop training or, worse, a misdiagnosis of drug-induced liver injury. 

But what if the very thing making the patient healthy is what is making their labs look pathological? Today we are breaking down a case that highlights a massive blind spot in modern clinical care where a completely expected lab finding is mistaken for clinical disease.

And to help us work through this problem like a pro, it’s the second most handsome dr

• Little bit of a different mystery case today. It’s not an emergency, but it is a big problem in medicine. 
• many doctors apparently miss this, with over half of physicians failing to include this diagnosis in their ddx 
• Every miss costs a lot of money and potentially, harm to the patient.
• That said, I know you’re going to get this 
• So, we can take our time and get the audience involved because there’s an almost 100% chance that this applies to them
• Ready?

Act 2 Consult

Consult (Patient Presentation)

Dr. Baraki, you’re working in clinic today and your 1st patient of the day comes in.

• He’s a 39 year old previously healthy male presents for lab follow up
• 6 months ago while in Asia he went to a clinic for some nausea and abdominal pain. He says he checked out fine, but they told him to follow up with his doctor when he got home because of his liver.
• He says he’s been fine, but was told he needed to follow up on his labs. 
• He subsequently went to another clinic, which tested his liver again. They said he needed a liver biopsy, which freaked him out. He heard you’re the best and he wanted a second opinion.
• He hands you the lab readout. It’s a liver panel test, which I’ll send you now.
  • As you can see, the lab test from Asia, 9 months ago, is pretty normal other than a modestly elevated alkaline phosphatase, which is 131, and gamma-glutamatly transferase – GGT- at 68.  
  • Since he’s been back in the states, he’s had an additional set of liver tests
    • It continues to show a modest elevations in alkaline phosphatase and GGT, but now also show elevated alanine transaminase —ALT, and aspartate transaminase –AST. Both are 1.5-2x the upper limit of normal. 

• • While you’re interviewing the patient, you glance at his vital signs in the chart. Everything is normal. Perhaps he’s been paying attention to the Barbell Medicine Vital 5. 

• You also notice that he appears well, without any gross abnormalities standing out to you. You’re a great multi-tasker.
• He takes no medications or supplements and denies use of drugs. He says he doesn’t think he has any family history of disease that he knows of. 
• When you ask him about any current abdominal pain, nausea, weight loss, or recent illness, he says nope, and then asks if he should be worried?! 
• Austin, I’ve got three questions for you: If you’re playing along at home, let’s see if you can answer these questions:
  • 1)What do you think about this patient?
  • 2) Can you take us through the different labs contained in a liver panel?
    • Transaminases like AST and ALT are universally grouped under standard “liver panels” and referred to as “liver function tests” (LFTs) or “liver enzymes.” This terminology is highly misleading because these enzymes are also abundant in skeletal muscle. This ingrained nomenclature creates a cognitive bias, leading physicians to immediately suspect hepatic pathology (like fatty liver, hepatitis, or alcohol abuse) rather than extrahepatic muscle damage.
    • Gamma-glutamyl transferase (GGT) has two primary roles: a specific biochemical function at the cellular level and a practical diagnostic role in clinical medicine.
      • Enzyme that  catalyzes the transfer of functional gamma-glutamyl groups to receptors
      • Production, recycling, and uptake  of glutathione, an essential antioxidant. 
      • Processing of foreign chemicals, inflammatory signaling, and nitric oxide signaling.
      • Not in mm, but many other cells like liver, pancreas, kidneys. 
      • highly sensitive for detecting hepatobiliary disease and cholestasis (impaired bile flow), though not specific to the liver 
      • useful for determining the origin of an elevated alkaline phosphatase (ALP) level. If ALP is elevated but GGT is normal, it indicates a bone disorder; if both are elevated, the issue is likely hepatic.
      • GGT is used to support suspicions of alcohol abuse, particularly in patients who present with an elevated aspartate aminotransferase (AST) level and an AST/ALT ratio greater than 2:1.
    • Alkaline Phosphatase (ALP): ALP is an enzyme found primarily in the liver and bone.
      • its levels remain unaltered by heavy muscular exercise.
    • Bilirubin is a metabolite of normal red blood cell breakdown that is processed by the liver. It is absent in muscle tissue, meaning that isolated muscle damage will not cause hyperbilirubinemia.
  • 3) What’s your differential diagnosis?
    • Viral hepatitis, specifically types a, b, and c.
      • assess the patient’s medical history for specific risk factors, and order targeted viral serologies.
        • Acute Viral Hepatitis: Acute infections typically present with marked enzyme elevations, characterized by AST and 
        • ALT levels greater than 25 times the upper limit of normal.
          • Hepatitis A: This virus is transmitted from person to person via the fecal-oral route, often through contaminated food. Clinicians will look for a history of this type of exposure.
          • Hepatitis B and C: These viruses are transmitted parenterally. Clinicians will look for risk factors such as intravenous drug use, a history of receiving a blood transfusion prior to 1992, travel to endemic areas, or known exposure to a patient with jaundice.
        • Chronic Hepatitis B: Enzyme levels vary depending on the disease state. They can be completely normal in inactive carriers, mildly to moderately elevated (approximately twice the upper limit of normal) in most patients, or spike to more than 10 times the normal limit during an acute exacerbation.
        • Chronic Hepatitis C: Aminotransferase levels have wide variability, typically ranging from normal to less than twice the upper limit of normal, and rarely exceed 10 times the normal limit.
    • Cirrhosis: If chronic viral hepatitis has progressed to cirrhosis, the patient may exhibit a pattern where AST is elevated higher than ALT, typically with an AST/ALT ratio between 1 and 2.
    • MASLD
    • DILI? 
    • Protein, creatine, too much exercise

Consult Diagnostic Work-Up

• The patient appears well, sitting in gym clothes, which are a bit sweaty, but the physical exam is unremarkable… including a through abdominal exam
  • Normal bowel sounds
  • No tenderness to palpation
  • No masses or enlargement of the liver or spleen 
  • No jaundice 
• You agree that it’d be a good idea to get some labs to see what’s going on now, and since the patient has no symptoms and is otherwise doing well, you agree to see him again next week. So, the patient is off to the lab to get some blood taken and, just to be safe, take a picture with an abdominal ultrasound. 
• Two days later, his labs come in.
• You ran serology for hepatitis a, b, and c. These viruses are the most common reason for an acute spike in transaminases because they attack the liver cells – the hepatocytes– and cause them to rupture. But the tests were negative.
• You also ran an electrophoresis for M-proteins, an antibody produced by specialized immune cells in a disease like multiple myeloma. If the cells in the blood are producing abnormal protein fragments, they can deposit in the liver and cause damage stress. It was negative.
• For some reason, the lab also tested for antimitochondrial antibodies. This is the specific marker for a disease called primary biliary cholangitis, a condition where the immune system decides to attack the small bile ducts or ductules within the liver. This test was negative as well. 
• And the penultimate test, the abdominal ultrasound looked for gallstones blocking a duct, a tumor, or significant fatty infiltration. This was also normal. 
• Finally, his repeat liver labs.
• His ALT and ALT continue to be elevated.
  • ALT about 2x upper limit of normal, AST more mild, but still elevated. His GGT is also elevated. 

• Austin, again I have three questions for you. Listeners, if you’re playing along at home, let’s see if you can answer them in the comments.
  • 1)Are you noticing an isolated transaminase elevation or a cholestatic pattern in these labs and what’s the significance?
    • An isolated transaminase elevation (increases in aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) indicates either hepatocellular (liver) injury or muscle damage. Because AST and ALT are present in skeletal muscle as well as the liver, an isolated rise in these enzymes is not specific to liver pathology. In healthy, physically active individuals, an isolated transaminase elevation is frequently the result of strenuous exercise, weightlifting, or muscle trauma, which causes damaged muscle cells to release these enzymes into the bloodstream.
    • In contrast, a cholestatic pattern involves the elevation of serum markers such as alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), bilirubin, and 5’-nucleotidase. The critical distinction is that these markers are not present in muscle tissue. Therefore, identifying a cholestatic pattern is highly valuable for confirming true liver damage and ruling out muscle injury.
    • To identify muscle damage: Clinicians should look for elevated levels of muscle-specific markers such as creatine kinase (CK) and myoglobin.
    • To identify liver damage: Clinicians should check for elevated levels of cholestatic serum markers, such as gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), bilirubin, and 5’-nucleotidase, which do not rise from muscle injury.
    • No CK, 
  • 2) How would you explain what’s going on with this patient?
    • When an athlete is told that their liver enzymes are “leaking” into their bloodstream—a physiological process where enzymes like AST and ALT escape from micro-torn skeletal muscle fibers after intense exercise—it often triggers considerable anxiety and distress. Because these biomarkers are universally, and somewhat misleadingly, referred to as “liver function tests,” athletes may immediately fear they are suffering from a major organ failure rather than experiencing a normal adaptation to their training.
    • This psychological impact typically manifests in several ways:
      • Fear of severe disease: An otherwise healthy, asymptomatic athlete may suddenly grapple with the distressing suspicion that they have developed a severe hepatic condition, such as fatty liver disease, hepatitis, or toxic liver damage.
      • The stress of the “diagnostic cascade”: The initial shock is frequently compounded by a stressful and unwarranted medical workup. To rule out liver pathologies, frightened athletes are often sent down a diagnostic pathway that includes expensive, time-consuming, and potentially invasive follow-up tests. This can involve extensive viral serologies, autoimmune screening, abdominal ultrasounds, and sometimes extreme measures like liver biopsies.
      • Medical hyper-vigilance: The acute psychological distress can lead athletes to alter their behavior, prompting them to visit multiple doctors to seek differing advice or to anxiously demand repeated blood tests just days apart to see if their enzyme levels are stabilizing
      • Ultimately, if a clinician fails to contextualize this “leaking” of enzymes as an expected consequence of vigorous muscle exertion, it results in unwarranted patient anxiety and a profound, unnecessary disruption to the athlete’s life and peace of mind. Simply obtaining a thorough exercise history and including muscle-specific tests (like creatine kinase) from the start could easily spare the athlete from this psychological burden.
  • 3) What’s your differential diagnosis?
    • Not Viral hepatitis
    • Non-alcoholic fatty liver disease, though less likely given his athletic profile and lack of metabolic syndrome.
    • Drug-induced liver injury from hidden ingredients in pre-workout supplements.
      • Supplements containing synephrine and caffeine have been directly associated with severe exercise-induced rhabdomyolysis (extreme muscle breakdown that releases AST and ALT into the blood). 
      • Ephedra, a banned sympathomimetic amine, was also linked to fatal rhabdomyolysis in wrestlers undergoing extreme exercise regimens, though they were concomitantly taking creatine
      • Many Oral Anabolic Androgenic Steroids (AAS)
      • Herbal and Dietary Supplements: Specific products and ingredients such as LipoKinetix, Hydroxycut, Garcinia cambogia, and Herbalife have been implicated in case reports of acute hepatitis, severe hepatotoxicity, or rhabdomyolysis.
    • Autoimmune hepatitis
      • antinuclear antibodies (ANA), anti-smooth muscle antibodies (ASMA), anti-liver/kidney microsomal antibodies type 1, and elevated Immunoglobulin G (IgG) levels
      • Women with previous AI disorder 
    • alpha-one antitrypsin deficiency.
      •  genetic disorder is considered especially if the patient has a history of early-onset emphysema
      • Alpha antitripysin protein is normally protective 
      • Test level and phenotyping
    • Exercise?
      • Creatine Kinase (CK): Checking CK is the most critical step, as elevated CK levels are a primary indicator of muscle injury. Massive elevations in CK evaluated alongside transaminases strongly indicate that muscle damage (such as exercise-induced rhabdomyolysis) is the true cause of the abnormal lab results, rather than liver disease.
      • Myoglobin: This is another intramuscular protein that routinely leaks into the serum alongside AST, ALT, and CK following intense physical exertion or muscle trauma.
      • Lactate Dehydrogenase (LDH) and Aldolase: These enzymes are also released into the extracellular space and bloodstream following severe muscle exertion. However, it should be noted that LDH is not entirely specific to muscle; while LDH isoenzymes (like LDH-5) exist, they are found in both skeletal muscle and the liver, limiting their value in perfectly distinguishing between the two.

The initial workup for this patient included viral markers and a liver ultrasound, all of which returned negative results. You’ve now ordered a 3rd set of labs, but the patient says he has some travel so he can’t get them done until 2 months later after he returns. He says he travels a lot for work, which he generally likes…other than the fact he doesn’t get to workout much like he does when he’s home. 

His new liver panel comes in where everything was normal. Normal liver associated enzymes, AST and ALT, normal GGT, alk-phos, bilirubin, you name it.

Okay, it’s question time once again for you Dr. Baraki, as well as the listeners at home:

1. How do you explain the resolved liver enzyme elevation? 
2. What’s your final diagnosis? 
3. How are you explaining this to the patient?

Act 3 Explanation/Mechanism

• The final diagnosis is exercise-induced liver associated tests.
  • The primary biological driver in this case is the release of intracellular enzymes from muscle cells into the systemic circulation following mechanical  stress. 
  •  Strenuous exercise depletes ATP and damages ion channels, leading to an electrolyte imbalance that floods the cell with intracellular calcium and sodium. This causes the cell to swell. Together, the cell swelling and electrolytes break down the muscle cells membrane – the sarcolemma– allowing intramuscular proteins like AST, ALT, and creatine kinase (CK) to leak into the extracellular space and bloodstream.
  • Point number 1: While alanine aminotransferase and aspartate aminotransferase are frequently referred to as “liver enzymes”, they are actually transaminases found in several tissues. aspartate aminotransferase is present in high concentrations in skeletal muscle, the heart, and kidneys, with alanine aminotransferase being in the muscle too, albeit a bit lower 
  • When a person engages in resistance training, especially training involving significant eccentric loading- where the muscle produces force as it gets longer- the downward phase of most exercises, the muscle experiences micro-trauma. This increases membrane permeability, allowing enzymes like creatine kinase, aspartate aminotransferase, and alanine aminotransferase to leak into the extracellular space and enter the bloodstream. This is normal physiology, and not a sign of liver dysfunction. 
  • Point number 2: It’s mostly unavoidable. In a study of 15 healthy men who lifted weights for 1 hour, 100% of the participants saw a bump in their liver associated tests, an average of about 3x normal for AST, and a smaller bump for ALT. This is more pronounced in people new to exercise or those coming back. However, lifelong trainees cannot avoid this entirely either, and that applies to both lifting and conditioning.
    • Generally speaking, the increases are less pronounced in veteran trainees, though the timeline is unaltered. It’s thought that the smaller increases are due to reduced muscle protein breakdown in trained individuals during a workout, increased plasma volume from long-term training, which dilutes the liver associated enzymes in the blood, and increased albumin production. As albumin binds to calcium and is responsible for transporting many things around the body, it may reduce the calcium-induced breakdown of the muscle cell’s sarcolemma. 
    • Men tend to be higher than women, as they generally have more muscle mass and higher baseline level of LAE
    • Genetic influences are strong, with some individuals being “high responders” to exercise- not in terms of seeing gainzZz, but in the release of higher volumes of enzymes than others
    • Other factors, such as exercising in hot or humid environments tend to produce higher levels of of LAE, as does alcohol consumption
  • Point number 3: It can take awhile to normalize. Based on available data, AST and ALT are continuing to rise 2 days post workout. They may take up to 4-5 days to peak, though they typically normalize by around 10-12 days…provided the person isn’t working out. Part of this delay is structural,  the muscle cell’s sarcolemma doesn’t degrade all at once, it’s a gradual process, which makes the intramuscular contents slowly leak out. Also, ALT tends to peak later – some studies suggesting as long as 6-7 days post workout. This could be influenced by the longer half life of ALT, which is 48 hours, as compared to AST, which is 17 hours. 
  • Point 4: It’s mostly harmless. The elevations of transaminases are strictly a transient, benign phenomenon representing skeletal muscle damage and repair, rather than a condition that leads to long-term hepatic issues. Because these enzymes leak from micro-torn skeletal muscle fibers rather than hepatocytes, the liver itself is unharmed and unaffected.
    • Even when an athlete presents with what appears to be a “chronic” elevation, the sources suggest this is actually just a persistent, fluctuating state of benign muscle turnover caused by their continuous training schedule. 
    • In this specific case, the patient actually had liver panel tests going back a decade showing mildly elevated AST and ALT. When the patient abstained from his regular running and resistance training for just seven days, his AST, ALT, and other markers completely normalized, demonstrating the total absence of any underlying, long-term hepatic pathology.
    • In fact, rather than indicating disease, researchers note that laboratory test results falling outside conventional reference ranges in physically active populations frequently mirror a healthy, physiological adaptation to regular training.
    • Therefore, the primary long-term consequence of these elevated enzymes for athletes is not medical or hepatic, but rather the risk of facing unwarranted psychological anxiety and an expensive, invasive “diagnostic cascade” (which can sometimes involve unnecessary liver biopsies) when physicians misinterpret these benign muscular adaptations as chronic liver disease.
• Speaking of which, Austin,in a survey of physicians given a case where a young, asymptomatic man had elevated LAE, 56% failed to list exercise-induced muscle damage in their DDX. Over 60% listed liver disease as their primary diagnosis. Why do you think clinicians often overlook exercise history in the context of screening asymptomatic young adults?
  • https://pubmed.ncbi.nlm.nih.gov/11476029/
  •  Discuss why clinicians often overlook exercise history in the context of screening asymptomatic young adults.
  • Clinicians often overlook exercise history when screening asymptomatic young adults for several systemic, cognitive, and educational reasons. Even though physical activity can drastically alter blood-based biomarkers, a patient’s exercise status is rarely considered when interpreting routine laboratory results.
  • The “Liver Function Test” Misnomer: Transaminases like AST and ALT are universally grouped under standard “liver panels” and referred to as “liver function tests” (LFTs) or “liver enzymes.” This terminology is highly misleading because these enzymes are also abundant in skeletal muscle. This ingrained nomenclature creates a cognitive bias, leading physicians to immediately suspect hepatic pathology (like fatty liver, hepatitis, or alcohol abuse) rather than extrahepatic muscle damage.
  • A Knowledge Gap in Primary Care: There is a well-documented educational gap among both primary care providers and specialists regarding how profoundly exercise can affect traditional liver markers. Some physicians simply forget that intense workouts—especially eccentric muscle training or heavy weightlifting—can cause these abnormalities. In some cases, even when an exercise history is provided, the physician may not believe that exercise alone could cause such highly pathological enzyme levels.
  • Reliance on General Reference Intervals: Laboratory results are generally interpreted using reference intervals established from the middle 95% of a healthy, average population. Clinicians often fail to recognize that results falling outside these typical ranges in young, highly active individuals might actually represent a normal, healthy adaptation to exercise training or expected tissue repair, rather than a disease state.
  • Omission of Muscle-Specific Biomarkers: Standard screening panels do not routinely include markers of muscle damage, such as creatine kinase (CK) or lactate dehydrogenase (LDH). When a clinician sees an isolated rise in AST and ALT without the context of a concurrently massive CK elevation, they are missing the most vital clue that points to skeletal muscle as the source of the enzymes.
  • The “Diagnostic Cascade” Reflex: Because routine checkups easily identify elevated enzymes in asymptomatic patients, physicians frequently launch straight into a traditional diagnostic pathway to rule out liver diseases. This often results in doctors ordering expensive viral panels, autoimmune markers, and abdominal ultrasounds without ever asking the patient about their recent workout habits or weightlifting regimens.
  • Ultimately, this oversight can lead to a waste of healthcare resources, unnecessary specialist referrals, extreme patient anxiety, and even invasive procedures like liver biopsies. The sources strongly advocate that a meticulous patient history must include exercise habits, and standard screenings for elevated transaminases should incorporate muscle biomarkers like CK to prevent these costly misdiagnoses.
• Point 5: GGT
  • The GGT Arbitrator:  ggt is a pretty good marker for the liver. If ggt is normal, the liver is likely an innocent bystander. Since it’s absent from muscle, it usually doesn’t rise post workout. Therefore, if a patient presents with highly elevated AST and ALT but a normal GGT (especially if muscle-specific markers like creatine kinase are high), the liver is simply an innocent bystander to exercise-induced muscle damage.
  • Alkaline phosphatase (ALP) is another enzyme commonly elevated in hepatobiliary diseases, particularly when bile flow is backed up.
    • However, ALP is also produced by bone. To determine whether an isolated ALP elevation is coming from the liver or the bone, clinicians use GGT as the definitive tie-breaker. 
    • Because GGT is sensitive to liver changes but is not produced by or increased in bone disorders, a normal GGT alongside an elevated ALP confidently confirms that the liver is unaffected. In this case, the liver is an innocent bystander, and the patient likely has a bone-related issue, such as a healing fracture, high bone turnover, osteomalacia, or Paget disease.
  • But…things are not so simple in medicine.
  • However, it can also be elevated post workout, albeit rarely if it was a particularly hard one.
    • Altered Hepatic Blood Flow: Strenuous exercise diverts blood away from internal organs and toward the skeletal muscles. This decrease in hepatic blood flow and oxygen saturation can temporarily increase the permeability of hepatocyte (liver cell) membranes, allowing liver enzymes like GGT to leak into the bloodstream
    • as it’s part of the repair process. We’ve discussed the breakdown of the muscle cell’s sarcolemma …well  certain enzymes actively assist in this recovery. GGT is one of these enzymes.
    •  GGT helps make component amino acids available to the cells for tissue repair. 
  • ALP-BONE TUNEROVER 
  • So, with an isolated elevation in AST and ALT, but normal GGT, I would feel pretty good about the cause being exercise…assuming the patient was exercising. Austin, what am I missing here? Specifically, the patient in our case did have an elevated GGT originally….did that throw you off the scent? 

Act 4 Takeaway

This case proves that a lab value without lifestyle context can be hard –and potentially costly– to interpret. 

Ultimately, the leakage of transaminases and even gamma-glutamyltransferase from exercised muscle cells myocytes—is well-documented. But there’s a disconnect between exercise science and modern medicine.

To start, there’s probably a cognitive bias stemming from calling these liver function tests, as that suggests a liver-only origin, which is not true.  They are present in many cells, including muscle, not just the liver. Yet because of that naming convention, it’s hard to look past the liver even when the patient is a perfectly healthy, asymptomatic athlete.

Next, physicians often don’t ask about exercise. It’s hard to come up with a solid number on this, but available data suggests less than half of patients in the primary care setting half any documentation of their exercise habits. 

My thought is that as a result of being liver-focused and exercise-agnostic, many clinicians see a slightly high ALT, they order the ultrasound, they run the hepatitis serology, and they repeat the panels—all without ever asking about the patient’s exercise habits. The costs of this can be immense, not only financially, but also in patient stress and anxiety. 

Austin, if you could waive a magic wand and change clinical practice overnight, how would you have doctors approach this issue the next time a lab result hits their inbox? 

• Ask about exercise
  • Counsel pls
• Assess
  • History, risk factors
  • Labs- HUGE elevation? 
  • Physical – spider nevi, palmar erythema, proximal muscle wasting, or a grossly enlarged, hard, nodular liver
  • Other labs, CK, LDH, myoglobin
• If reassured, repeat labs first, if anything
  • GGT

For listeners who may be dealing with a skeptical primary care physician, there are a few strategies you can use to avoid unnecessary care without risking a big-time miss of a serious condition.

• Inform your doc
  •  engage in heavy resistance training/endurance exercise, and I worked out shortly before my last blood draw. I understand that intense exercise causes muscle micro-tearing, which leaks enzymes like AST and ALT into the blood and can look like liver damage
  • Medical literature notes that these enzymes can remain elevated for up to a week after intense exercise. Before we proceed with imaging or specialist referrals, I would like to abstain from all strenuous exercise for a full seven days and then repeat the blood panel to see if my levels normalize
    • no training for a week before labs 
• For those who want to avoid taking a week off….could ask
  • When we repeat the test, could we please add a check for Creatine Kinase (CK) and Lactate Dehydrogenase (LDH)? If my CK is highly elevated alongside the AST and ALT, it would confirm that the enzymes are coming from my muscles rather than my liver.”
• For the minimalist
  • Since I am completely asymptomatic, standard guidelines suggest that mild to moderate elevations (less than five times the upper limit of normal) can be safely monitored with expectant observation. I’d prefer to watch and wait, with a re-test in 4-6 weeks. 
• Austin, any other tips for our would-be patients?

So What

The reality is that lab data is only as useful as the context it is gathered in. If we don’t account for how a patient actually lives – or even ask about it– we are not practicing medicine, we’re just reading a spreadsheet. For the active patient, many lab results can be abnormally high. Knowing when to be worried and when to chill takes practice, starting with asking patients about their exercise habits. 

Read the full clinical breakdown