Glutamine
L-Glutamine is the most abundant free amino acid in the human body, functioning as a conditionally essential nutrient during periods of severe metabolic stress, trauma, or critical illness. It serves as the primary energetic fuel source for rapidly dividing cells, particularly intestinal enterocytes and immune lymphocytes. By maintaining the integrity of the intestinal mucosal barrier and supporting cellular glutathione synthesis, high-dose glutamine supplementation is widely utilized to repair increased intestinal permeability, accelerate surgical or athletic recovery, and mitigate the gastrointestinal toxicity of certain chemotherapies.
Key Takeaways
- •Acts as the preferred respiratory fuel for enterocytes (the cells lining the intestinal tract), making it indispensable for maintaining the structural integrity of the gut barrier and preventing the systemic translocation of luminal endotoxins.
- •Functions as a conditionally essential amino acid; while the body synthesizes it abundantly under normal conditions, severe physiological stress (like burns, sepsis, or intense endurance exercise) rapidly depletes intramuscular stores, necessitating exogenous supplementation.
- •Provides critical support to the immune system by fueling the proliferation and phagocytic activity of macrophages and lymphocytes, reducing the incidence of secondary infections in critically ill and post-surgical populations.
- •Serves as a crucial precursor for the synthesis of glutathione, the master endogenous antioxidant, thereby enhancing cellular defense against oxidative stress and mitigating tissue damage during severe systemic inflammation.
- •Stimulates muscle protein synthesis and inhibits protein breakdown by facilitating the cellular uptake of leucine, which subsequently activates the mTORC1 signaling pathway, a key driver of muscular hypertrophy and repair.
- •Utilized as an adjunctive therapy in specific oncology settings to reduce the severity of chemotherapy-induced mucositis and stomatitis, supporting patient quality of life and treatment tolerance.
- •Requires high-dose, powder-form administration (often exceeding 10 grams daily) to achieve therapeutic concentrations in the gut, as the intestinal lining intercepts and metabolizes the vast majority of ingested glutamine before it reaches systemic circulation.
Basic Information
- Name
- Glutamine
- Also Known As
- L-Glutamine2-Amino-4-carbamoylbutanoic acidLevoglutamide
- Category
- Conditionally Essential Amino Acid
- Bioavailability
- The systemic bioavailability of orally ingested glutamine is notoriously low, as it is aggressively extracted by the splanchnic bed during first-pass metabolism. Approximately 50 to 80 percent of an oral dose is rapidly consumed by the enterocytes of the small intestine and the immune cells within the gut-associated lymphoid tissue (GALT). While this makes oral glutamine exceptionally effective for targeting gastrointestinal pathologies, it necessitates high, multi-gram dosing to significantly elevate systemic plasma concentrations for muscle or immune support.
- Half-Life
- Following oral or intravenous administration, exogenous glutamine is rapidly cleared from the plasma, exhibiting a very short half-life of approximately 1 to 2 hours. It is immediately taken up by the liver, kidneys, and skeletal muscle for metabolic processing, gluconeogenesis, or incorporation into proteins. Due to this rapid cellular uptake and short plasma residence time, therapeutic regimens typically divide the total daily dose into multiple smaller administrations throughout the day.
Primary Mechanisms
Provision of primary oxidative fuel (ATP generation) for rapidly dividing cells, specifically enterocytes and lymphocytes
Upregulation of tight junction proteins (claudin-1, occludin), restoring intestinal barrier integrity
Serving as an obligatory nitrogen donor for the biosynthesis of purines and pyrimidines necessary for DNA and RNA synthesis
Supplying the precursor glutamate for the synthesis of intracellular glutathione, enhancing antioxidant capacity
Facilitating the transport of ammonia from peripheral tissues to the liver and kidneys, regulating systemic acid-base balance
Activating the mTORC1 signaling cascade (in concert with leucine) to stimulate skeletal muscle protein synthesis
Modulating the cellular heat shock response, increasing the expression of heat shock proteins that protect against cellular stress
Quick Safety Summary
For gastrointestinal repair and general athletic recovery, doses typically range from 5 to 15 grams per day, taken in divided doses. In clinical settings for severe trauma, burns, or chemotherapy-induced mucositis, doses are significantly higher, often ranging from 20 to 40 grams per day. Doses up to 0.5 grams per kilogram of body weight per day have been used safely in short-term critical care interventions. However, doses exceeding 40 grams per day are generally not recommended outside of intensive medical supervision.
Severe hepatic encephalopathy: In end-stage liver disease, the liver cannot process the ammonia generated from glutamine metabolism, potentially exacerbating neurological symptoms, Bipolar disorder and seizure history: Glutamine is a direct precursor to the excitatory neurotransmitter glutamate; high doses may theoretically lower the seizure threshold or trigger manic episodes in susceptible individuals, Monosodium glutamate (MSG) sensitivity: Individuals highly sensitive to dietary MSG often report adverse neurological symptoms (headaches, agitation) when consuming high-dose isolated glutamine, Certain active malignancies: While used to treat chemotherapy side effects, some rapidly growing tumors are "glutamine-addicted" and utilize it for aggressive growth; use in active cancer should be guided by an oncologist
Overview
L-Glutamine is the most abundant amino acid in the human body, accounting for approximately 60 percent of the free amino acid pool in skeletal muscle and 20 percent of circulating plasma amino acids. Under normal physiological conditions, the body synthesizes adequate amounts of glutamine, primarily within skeletal muscle and the lungs, classifying it as a non-essential amino acid. However, this classification abruptly changes during periods of severe metabolic stress, such as major surgery, severe burns, sepsis, exhaustive endurance exercise, or acute gastrointestinal disease. During these hypercatabolic states, the demand for glutamine by the immune system and the gastrointestinal tract vastly exceeds the body's endogenous synthetic capacity, rapidly depleting intramuscular stores. In these scenarios, glutamine becomes a 'conditionally essential' nutrient, making exogenous supplementation critical for survival and recovery.
The gastrointestinal tract is the largest consumer of glutamine in the body. The enterocytes that line the small and large intestines exhibit a remarkably high turnover rate, completely renewing every few days. These rapidly dividing cells paradoxically prefer glutamine over glucose as their primary respiratory fuel. By oxidizing glutamine, enterocytes generate the ATP necessary to power the massive energy requirements of nutrient absorption and barrier maintenance. Furthermore, glutamine is strictly required for the synthesis of tight junction proteins, the structural anchors that seal the microscopic gaps between intestinal cells. When systemic glutamine drops, these tight junctions degrade, leading to increased intestinal permeability. This 'leaky gut' allows luminal antigens, endotoxins, and intact bacteria to translocate into the portal circulation, triggering systemic inflammation and placing a massive detoxification burden on the liver.
Beyond its structural role in the gut, glutamine is a foundational pillar of the cellular immune response and systemic antioxidant defense. Lymphocytes, macrophages, and neutrophils share the enterocyte's dependency on glutamine for energetic fuel. When an immune response is triggered, these cells undergo massive clonal expansion, a process requiring vast amounts of DNA and RNA. Glutamine serves as the obligatory nitrogen donor for the biosynthesis of the purine and pyrimidine bases that form these nucleic acids. Without sufficient glutamine, the immune system cannot mount a rapid, proliferative defense against pathogens. Concurrently, glutamine is one of the three precursor amino acids (alongside cysteine and glycine) required for the intracellular synthesis of glutathione, the body's most critical endogenous antioxidant. By ensuring adequate glutathione production, glutamine protects tissues from the severe oxidative damage characteristic of critical illness and intense physical exertion.
The clinical application of glutamine has evolved significantly from its origins in intensive care units to broad applications in gastroenterology, sports nutrition, and supportive oncology. For athletes, it accelerates glycogen resynthesis and cellular hydration, reducing the delayed-onset muscle soreness and immunosuppression associated with overtraining. In oncology, high-dose oral protocols are routinely employed to prevent and treat the severe, dose-limiting mucosal ulcerations (mucositis) caused by radiation and specific chemotherapies. Despite its ubiquitous presence in the diet, the strategic use of isolated, high-dose glutamine leverages its unique pharmacokinetic profile: because the splanchnic bed intercepts the vast majority of an oral dose, massive local concentrations are achieved in the intestinal mucosa, providing targeted, rapid repair of the gastrointestinal barrier.
Core Health Impacts
- • Intestinal permeability and gut barrier function: Glutamine is universally recognized as the premier nutrient for gut lining repair. In conditions characterized by increased intestinal permeability, colloquially termed leaky gut, the tight junction proteins linking enterocytes degrade. Clinical studies demonstrate that glutamine supplementation upregulates the expression of tight junction proteins like claudin-1 and occludin. By providing direct energy to enterocytes, it accelerates mucosal regeneration and significantly reduces the translocation of pathogenic bacteria and endotoxins into the bloodstream, making it a foundational treatment for inflammatory bowel diseases and irritable bowel syndrome.
- • Chemotherapy and radiation-induced mucositis: Oncological treatments often cause severe collateral damage to the rapidly dividing cells of the gastrointestinal tract, resulting in painful mucositis. Meta-analyses of randomized trials indicate that prophylactic high-dose oral glutamine significantly reduces the incidence, severity, and duration of oral stomatitis and intestinal mucositis induced by specific chemotherapeutic regimens and radiation therapy. This mucosal protection helps maintain nutritional status, reduces the need for opioid analgesia, and minimizes treatment interruptions.
- • Post-surgical and trauma recovery: Major surgery, severe burns, and trauma trigger a hypercatabolic state characterized by profound muscle wasting and a massive drain on systemic glutamine pools. In intensive care settings, glutamine-enriched enteral or parenteral nutrition is consistently associated with improved nitrogen balance, accelerated wound healing, and a significant reduction in hospital-acquired infections. The restoration of glutamine levels blunts the catabolic response and provides the necessary substrates for the intense immune and reconstructive activity required during recovery.
- • Muscle recovery and athletic performance: During prolonged, exhaustive exercise, plasma glutamine levels plummet, which is strongly correlated with the immunosuppression often observed in overtrained athletes. Supplementation mitigates this decline, reducing the incidence of upper respiratory tract infections post-exercise. Furthermore, by increasing cell volumization and promoting glycogen resynthesis, glutamine accelerates muscular recovery between training sessions, decreases delayed-onset muscle soreness, and protects against exercise-induced muscle protein breakdown.
- • Immune system modulation: Lymphocytes and macrophages are uniquely dependent on glutamine for energy generation and nucleotide synthesis during clonal expansion. When plasma glutamine concentrations fall below physiological thresholds, the proliferation of T-cells and the phagocytic capacity of macrophages are severely impaired. Supplemental glutamine restores these functions, enhancing the early immune response to pathogens and maintaining immune surveillance during periods of high physiological or psychological stress.
- • Hepatic lipid metabolism and NAFLD: Emerging clinical evidence suggests a role for glutamine in managing non-alcoholic fatty liver disease (NAFLD). In randomized trials, glutamine supplementation in patients with NAFLD led to significant reductions in liver enzymes and hepatic fat accumulation independent of weight loss. The mechanism is believed to involve the modification of the gut microbiome, the reduction of gut-derived endotoxemia reaching the liver via the portal vein, and the direct enhancement of hepatic antioxidant capacity through increased glutathione synthesis.
- • Burn injury management: Severe burn injuries induce the most profound depletion of systemic glutamine observed in clinical medicine. Standard treatment protocols in major burn centers often include high-dose enteral glutamine to support the massive metabolic demands of the regenerating epidermis and the hyperactive immune system. Studies confirm that this targeted supplementation decreases mortality rates, shortens the duration of bacteremia, and accelerates graft healing in severe burn patients.
Gene Interactions
Key Gene Targets
DPYD
Patients with DPYD variants face severe gastrointestinal toxicity (mucositis and diarrhea) from fluoropyrimidine chemotherapies; high-dose oral glutamine is frequently utilized as a supportive intervention to accelerate intestinal mucosal repair and restore gut barrier integrity during these severe toxicity events, although it does not alter the underlying metabolic deficiency of the DPYD enzyme.
Safety & Dosing
Contraindications
Severe hepatic encephalopathy: In end-stage liver disease, the liver cannot process the ammonia generated from glutamine metabolism, potentially exacerbating neurological symptoms
Bipolar disorder and seizure history: Glutamine is a direct precursor to the excitatory neurotransmitter glutamate; high doses may theoretically lower the seizure threshold or trigger manic episodes in susceptible individuals
Monosodium glutamate (MSG) sensitivity: Individuals highly sensitive to dietary MSG often report adverse neurological symptoms (headaches, agitation) when consuming high-dose isolated glutamine
Certain active malignancies: While used to treat chemotherapy side effects, some rapidly growing tumors are "glutamine-addicted" and utilize it for aggressive growth; use in active cancer should be guided by an oncologist
Drug Interactions
Lactulose: Often used to treat hepatic encephalopathy by reducing ammonia; glutamine administration directly counteracts this effect by increasing systemic ammonia loads
Chemotherapy agents: While generally protective against side effects, there is theoretical concern that extreme glutamine supplementation could provide fuel for specific glutamine-dependent tumor types during active treatment
Anticonvulsants (valproate, gabapentin): The conversion of glutamine to excitatory glutamate may mildly antagonize the mechanism of drugs designed to suppress central nervous system excitability
Common Side Effects
Generally exceptionally well tolerated at doses under 15 grams per day
Mild gastrointestinal distress, including bloating and altered bowel habits, occasionally occurs upon initiation of high-dose therapy
Neurological symptoms such as anxiety, restlessness, or headache can occur in sensitive individuals due to rapid conversion to the excitatory neurotransmitter glutamate
Studied Doses
For gastrointestinal repair and general athletic recovery, doses typically range from 5 to 15 grams per day, taken in divided doses. In clinical settings for severe trauma, burns, or chemotherapy-induced mucositis, doses are significantly higher, often ranging from 20 to 40 grams per day. Doses up to 0.5 grams per kilogram of body weight per day have been used safely in short-term critical care interventions. However, doses exceeding 40 grams per day are generally not recommended outside of intensive medical supervision.
Mechanism of Action
Enterocyte Energetics and Tight Junction Regulation
The most profound pharmacological effect of glutamine occurs within the gastrointestinal tract. Enterocytes, the columnar epithelial cells lining the intestines, undergo a complete cellular turnover every three to five days, a process requiring massive energetic expenditure. Unlike most human cells that rely heavily on glucose, enterocytes preferentially oxidize glutamine. The mitochondrial enzyme glutaminase converts glutamine into glutamate, which is then transformed into alpha-ketoglutarate and fed directly into the citric acid cycle for rapid ATP generation. This preferential fuel source is essential for maintaining the structural integrity of the gut lining. Crucially, glutamine oxidation regulates the expression and assembly of tight junction proteins. It activates specific intracellular kinases (such as MAPK and PI3K) that increase the transcription of claudin-1 and occludin, the proteins responsible for sealing the paracellular spaces between enterocytes. By actively maintaining these tight junctions, glutamine prevents the translocation of luminal bacteria and endotoxins into the portal circulation, thereby neutralizing the primary driver of systemic, gut-derived inflammation.
Immune Cell Proliferation and Nucleotide Synthesis
Glutamine is an indispensable substrate for the cellular immune system. During an active immune response, lymphocytes and macrophages undergo rapid clonal expansion and require immense biosynthetic resources. While glucose provides the carbon backbone, glutamine acts as the obligatory nitrogen donor for the synthesis of purine and pyrimidine nucleotides, the essential building blocks for new DNA and RNA. Without sufficient plasma glutamine, the proliferative capacity of T-cells and B-cells is severely blunted. Furthermore, macrophages require high intracellular concentrations of glutamine to fuel the oxidative burst necessary for phagocytosis and the destruction of engulfed pathogens. During severe physiological stress, the rapid depletion of muscle glutamine stores starves the immune system, leading to the profound immunosuppression often observed in critical illness, major trauma, and severe overtraining. Exogenous supplementation rapidly corrects this deficit, restoring immune competence and reducing the incidence of secondary infections.
Glutathione Biosynthesis and Antioxidant Defense
Glutamine is a critical upstream precursor for the synthesis of glutathione, the most abundant and important endogenous antioxidant in human cells. Glutathione is a tripeptide composed of glutamate, cysteine, and glycine. Following cellular uptake, glutamine is rapidly deaminated by glutaminase to form glutamate, bypassing the rate-limiting steps of endogenous glutamate synthesis during high stress. This glutamate is then combined with cysteine to form gamma-glutamylcysteine, the direct precursor to glutathione. In conditions characterized by massive oxidative stress and inflammation, such as severe burns or sepsis, intracellular glutathione is rapidly depleted as it neutralizes reactive oxygen species. By providing massive amounts of the glutamate substrate, glutamine supplementation ensures that the cellular machinery can continuously regenerate glutathione, protecting lipid membranes and mitochondrial DNA from catastrophic oxidative damage and maintaining cellular viability in hypermetabolic states.
Epigenetic Modulation
High-dose glutamine administration influences cellular gene expression through metabolic and epigenetic pathways. Glutamine metabolism heavily influences the intracellular ratio of alpha-ketoglutarate (a product of glutamine oxidation). Alpha-ketoglutarate acts as an essential cofactor for the Ten-Eleven Translocation (TET) family of enzymes, which are responsible for active DNA demethylation, and for Jumonji C-domain-containing histone demethylases. By supplying a massive influx of alpha-ketoglutarate, glutamine alters the epigenetic landscape, removing repressive methylation marks from specific gene promoters. This epigenetic remodeling is particularly relevant in the intestinal mucosa, where it facilitates the rapid transcription of genes required for cellular differentiation and mucosal repair in response to injury or inflammatory damage. Additionally, glutamine regulates the expression of specific microRNAs that control the inflammatory phenotype of intestinal epithelial cells, providing a mechanism for long-term resolution of gut inflammation.
mTORC1 Activation and Muscle Protein Synthesis
In skeletal muscle, glutamine operates synergistically with essential amino acids, specifically leucine, to regulate protein synthesis. The intracellular concentration of glutamine controls the cellular uptake of leucine through a specialized bidirectional amino acid transporter (SLC7A5). Glutamine is exported out of the cell in direct exchange for the importation of extracellular leucine. Once inside the cell, leucine potently activates the Mammalian Target of Rapamycin Complex 1 (mTORC1), the master kinase that initiates mRNA translation and muscular hypertrophy. Therefore, when intramuscular glutamine levels crash during severe stress or exercise, the cell loses its ability to import leucine, effectively shutting down protein synthesis and accelerating catabolism. Restoring glutamine pools re-establishes this transport mechanism, activating mTORC1, blunting muscle protein breakdown, and promoting a positive nitrogen balance necessary for structural recovery.
Clinical Evidence
Mucosal Healing and Leaky Gut Syndrome
Clinical trials have robustly validated the use of glutamine for restoring intestinal barrier function. In randomized, double-blind trials involving patients with post-infectious irritable bowel syndrome (IBS-D) characterized by measured intestinal hyperpermeability, high-dose oral glutamine (typically 15 grams daily) significantly reduced bowel frequency and normalized intestinal permeability scores (measured via the lactulose/mannitol ratio). In patients with inflammatory bowel diseases such as Crohn disease, supplemental glutamine has been shown to reduce inflammatory cytokine profiles in the colonic mucosa and accelerate the healing of ulcerations during remission phases. The overwhelming consensus in gastroenterology supports glutamine as a foundational, safe intervention for mechanically repairing the gut lining following severe insults, chronic NSAID use, or dysbiosis.
Supportive Oncology and Mucositis
One of the most evidence-based applications of high-dose glutamine is in supportive oncology. Radiation therapy and high-dose chemotherapy regimens (particularly 5-fluorouracil and methotrexate) frequently cause severe mucositis - painful ulcerations extending from the mouth through the entire gastrointestinal tract. Multiple meta-analyses have concluded that prophylactic administration of oral glutamine significantly reduces the incidence and severity of both oral stomatitis and intestinal mucositis. Patients receiving glutamine require fewer days of total parenteral nutrition, experience less severe diarrhea, and require significantly less opioid analgesia. The “swish and swallow” protocol ensures that the amino acid directly coats the oral mucosa before providing systemic benefits to the lower intestinal tract, representing a standard of care in many advanced oncology protocols.
Critical Care, Trauma, and Burn Recovery
The application of glutamine in critical care medicine has been extensively studied for decades. In major burn centers, severe trauma units, and post-surgical recovery, the body enters a profound hypercatabolic state, draining systemic glutamine stores to critically low levels. Large randomized controlled trials demonstrate that supplementing enteral or parenteral nutrition with high doses of glutamine significantly improves nitrogen balance, indicating a halt to muscle wasting. More importantly, these trials consistently show dramatic reductions in hospital-acquired infections (such as pneumonia and sepsis), directly validating glutamine’s role in sustaining the cellular immune system. Meta-analyses confirm that appropriate glutamine supplementation in specific critically ill populations shortens intensive care unit stays and significantly reduces overall hospital mortality.
Athletic Recovery and Overtraining
In the realm of sports nutrition, glutamine is widely utilized to mitigate the physiological consequences of intense training. While clinical data do not support glutamine as a direct performance-enhancing ergogenic aid (it will not acutely increase strength or speed), it is highly effective for recovery. Studies monitoring elite endurance athletes demonstrate that plasma glutamine drops precipitously following events like marathons, creating an “open window” of immunosuppression lasting several hours. Athletes supplemented with glutamine post-exercise show a significantly lower incidence of upper respiratory tract infections in the following weeks compared to placebo groups. Additionally, glutamine supplementation enhances the rate of muscle glycogen resynthesis when combined with carbohydrates and decreases the biochemical markers of muscle damage, allowing for greater training volume and consistency over the competitive season.
Dosing Guidance
The effective dosing of glutamine requires a strategy vastly different from standard capsulated supplements. For general intestinal health and mild recovery, a daily dose of 5 to 10 grams is standard. For addressing active “leaky gut” or inflammatory bowel conditions, doses of 15 to 20 grams per day, divided into three separate administrations, are common. In clinical scenarios such as chemotherapy-induced mucositis, trauma recovery, or severe burns, doses often range from 20 to 40 grams daily under medical supervision. Glutamine should always be consumed in powder form, mixed in cold or room-temperature water, as heat rapidly denatures the amino acid. To maximize absorption and prevent competition with other dietary proteins for intestinal transport, it is highly recommended to take glutamine on an empty stomach, either first thing in the morning or between major meals. Due to potential rapid conversion to excitatory neurotransmitters, individuals should start with a lower dose (e.g., 2 to 5 grams) and gradually titrate upward to assess individual neurological tolerance.
Getting the Most from Glutamine
Prioritize pure L-Glutamine powder. It is tasteless, mixes easily into water, and is vastly more cost-effective than capsulated forms for achieving the high doses required for gastrointestinal repair.
Timing is critical for gut healing; taking your dose first thing in the morning on an empty stomach or right before bed ensures the amino acid reaches the intestinal lining without competition from dietary proteins.
If utilizing glutamine for oral mucositis (mouth sores from chemotherapy), mix the powder with a small amount of water, vigorously swish it around the mouth for a full minute to coat the oral mucosa, and then swallow.
Be vigilant about the temperature of your mixing liquids; mixing glutamine into hot tea or coffee denatures the molecule. Always use cold or room-temperature fluids.
If you experience anxiety, restlessness, or difficulty sleeping after initiating therapy, you may be rapidly converting glutamine into the excitatory neurotransmitter glutamate. Reduce the dose significantly and take it exclusively in the morning.
For comprehensive gut repair, consider combining glutamine with other mucosal supportive agents such as zinc carnosine, deglycyrrhizinated licorice (DGL), and a high-quality probiotic, as they work synergistically on different aspects of barrier integrity.
Relevant Research Papers
Links go to PubMed (abstracts are public); some papers also offer free full text via PMC or the publisher.
A landmark meta-analysis demonstrating that glutamine supplementation in critically ill patients significantly reduces the rate of infectious complications and decreases overall hospital mortality.
A comprehensive review detailing the precise molecular mechanisms by which glutamine regulates tight junction proteins and protects the intestinal epithelium against various physiological stressors.
Confirms that high-dose oral glutamine significantly reduces the duration and severity of chemotherapy-induced mucositis and diarrhea, establishing its role in supportive oncology.
Details the absolute requirement of glutamine for lymphocyte proliferation and macrophage function, highlighting its indispensable role in maintaining systemic immune competence.
Provides foundational physiological evidence that removing glutamine from nutrition rapidly induces intestinal atrophy, while supplementation drives robust mucosal regeneration and villus growth.
Demonstrates that glutamine supplementation following exhaustive exercise blunts the post-exercise drop in plasma glutamine, significantly reducing the subsequent incidence of upper respiratory tract infections.
Clinical trial showing that targeted enteral glutamine in severe burn injuries improves immune function, accelerates wound healing, and dramatically reduces the length of hospital stay.
Outlines the biochemical pathway by which exogenous glutamine serves as the rate-limiting precursor for hepatic glutathione synthesis, protecting the liver from severe oxidative and toxic insults.