Glutathione: Your Body’s Master Antioxidant

Last Updated: March 1, 2026 | Author: Mike Hartnett | Category: Longevity Supplements

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Glutathione: Why Longevity Researchers Call It the Master Antioxidant

If you follow longevity science at all, you have almost certainly encountered glutathione. It appears in the protocols of researchers, the supplement stacks of biohackers, and the clinical literature on aging, liver health, and immune function. Yet despite its outsized reputation, glutathione remains one of the most misunderstood supplements on the market — largely because the question of whether oral supplementation actually raises intracellular levels has been debated for decades.

Dr. Rhonda Patrick has discussed glutathione extensively on her FoundMyFitness platform, emphasizing its role in managing oxidative stress and its connections to cellular defense pathways. David Sinclair’s research into NAD+ and sirtuin biology intersects with glutathione metabolism, since NAD+ dependent enzymes support the recycling of oxidized glutathione back to its active reduced form. Peter Attia has addressed glutathione in the context of liver health and detoxification on The Drive podcast, noting the clinical use of N-acetylcysteine (NAC) as a glutathione precursor in hospital settings.

Important: This article reports on published research and expert discussions about glutathione. We are not recommending specific supplements or dosages. Nothing in this article constitutes medical advice. Consult a qualified healthcare provider before making changes to your supplement regimen.

What Is Glutathione?

Answer capsule: Glutathione is a tripeptide molecule composed of three amino acids — glutamate, cysteine, and glycine — produced naturally in every cell of the body. It serves as the primary intracellular antioxidant, plays a central role in phase II liver detoxification, supports immune cell function, and is essential for DNA synthesis and repair. Researchers frequently refer to it as the body’s “master antioxidant” because it regenerates other antioxidants like vitamins C and E.

Unlike most antioxidants you consume through food, glutathione is synthesized inside your cells through a two-step enzymatic process. The rate-limiting factor in this process is cysteine availability, which is why NAC (N-acetylcysteine) — a cysteine donor — has been used clinically as a glutathione precursor for decades.

Glutathione exists in two forms within the body: the reduced form (GSH) and the oxidized form (GSSG). The ratio of GSH to GSSG is considered a key biomarker of cellular health and oxidative stress. When cells are under stress, GSH donates electrons to neutralize reactive oxygen species and becomes GSSG. Healthy cells maintain a ratio heavily weighted toward the reduced GSH form — research published in Free Radical Biology and Medicine has noted that a GSH:GSSG ratio above 100:1 is typical in healthy cells, and that this ratio declines significantly with age and disease.

The Four Core Functions of Glutathione

1. Antioxidant defense. Glutathione neutralizes free radicals and reactive oxygen species directly. It also regenerates vitamins C and E after they have been oxidized, effectively recycling the body’s antioxidant network. A 2003 review published in the Journal of Nutrition described glutathione as the most abundant low-molecular-weight thiol in mammalian cells and the central hub of the antioxidant defense system.

2. Detoxification. In the liver, glutathione conjugates with toxins, drugs, and metabolic waste products through a process called glutathione conjugation (phase II detoxification). This reaction, catalyzed by glutathione S-transferase (GST) enzymes, makes toxic compounds water-soluble so they can be excreted. This mechanism is so fundamental that NAC, the glutathione precursor, is the standard hospital treatment for acetaminophen (Tylenol) overdose.

3. Immune function. Glutathione is essential for the proliferation and function of lymphocytes, particularly T cells and natural killer (NK) cells. Research published in Proceedings of the National Academy of Sciences has demonstrated that glutathione depletion impairs T cell activation, while repletion restores it. Dr. Rhonda Patrick has noted that glutathione status is a key determinant of immune resilience, particularly in older adults whose levels have declined.

4. Cellular repair and protein synthesis. Glutathione participates in DNA synthesis and repair, amino acid transport across cell membranes, and the regulation of cell proliferation and apoptosis. It also maintains the thiol groups on proteins, protecting them from irreversible oxidative damage.

For more on how different longevity researchers approach antioxidant and cellular defense supplementation, see our guide: What Longevity Experts Agree and Disagree On in 2026.

Why Glutathione Declines With Age

Answer capsule: Glutathione levels decline progressively after age 30 due to reduced synthesis capacity, increased oxidative demands, chronic stress, environmental toxin exposure, alcohol consumption, poor diet, and declining levels of precursor amino acids. Research published in The Journals of Gerontology has documented that glutathione concentrations drop by 10-15% per decade after the age of 45, accelerating further in the presence of chronic disease.

The decline in glutathione is not a single-mechanism problem. It is driven by multiple converging factors, all of which worsen with age.

Reduced Synthesis Capacity

The enzymes responsible for glutathione synthesis — glutamate-cysteine ligase (GCL) and glutathione synthetase — become less active with age. A 2004 study published in The American Journal of Clinical Nutrition by researchers at Baylor College of Medicine found that older adults had significantly lower rates of glutathione synthesis compared to younger adults, and that supplementing with the precursor amino acids glycine and cysteine (via NAC) restored synthesis rates and GSH levels within two weeks.

Increased Oxidative Demand

As mitochondrial function declines with age, reactive oxygen species (ROS) production increases. This means the body consumes glutathione faster while simultaneously producing it more slowly. David Sinclair’s research into NAD+ decline and aging intersects here — the NAD+-dependent sirtuins support the enzymatic recycling of GSSG back to GSH. As NAD+ levels fall, the capacity to recycle oxidized glutathione diminishes, compounding the depletion. For a detailed look at Sinclair’s NAD+ research and how it connects to broader cellular defense, see our David Sinclair Protocol Guide.

Environmental Toxins and Lifestyle Factors

Every toxin the liver processes draws on the glutathione pool. Chronic exposure to air pollution, heavy metals, pesticides, alcohol, and pharmaceutical drugs accelerates glutathione depletion. Alcohol is particularly impactful — a 2000 study in Hepatology demonstrated that chronic alcohol consumption depletes hepatic glutathione by as much as 50%, severely compromising the liver’s detoxification capacity.

• Alcohol: Even moderate consumption depletes liver glutathione. Heavy drinking can reduce hepatic GSH by 40-50%.
• Acetaminophen (Tylenol): One of the most common over-the-counter medications, it is metabolized by the liver using glutathione. Overdose overwhelms GSH reserves, which is why NAC is the standard emergency treatment.
• Air pollution and heavy metals: Particulate matter, lead, mercury, and arsenic all consume glutathione during detoxification.
• Chronic stress: Elevated cortisol increases oxidative stress, accelerating glutathione turnover.
• Poor protein intake: Since glutathione synthesis requires glycine, cysteine, and glutamate, inadequate protein consumption limits production.

The Vicious Cycle

Glutathione depletion creates a self-reinforcing cycle. Lower GSH levels mean less antioxidant protection, which means more oxidative damage to mitochondria, which means more ROS production, which further depletes glutathione. Breaking this cycle is one of the primary goals of glutathione supplementation — and why researchers continue to investigate whether supplementation can meaningfully restore levels in aging adults.

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Frequently Asked Questions

The Bioavailability Debate: Does Oral Glutathione Work?

Answer capsule: The central challenge with glutathione supplementation is bioavailability. Standard (unformulated) oral glutathione was long considered poorly absorbed because digestive enzymes break down the tripeptide before it reaches the bloodstream. However, research over the past decade — particularly on liposomal delivery systems — has challenged this assumption. The debate now centers not on whether oral glutathione can raise blood levels, but on which form delivers the most reliable increase in intracellular GSH.

For years, the conventional wisdom in both clinical and supplement communities was straightforward: oral glutathione does not work. The tripeptide is broken down by peptidases in the gut before it can be absorbed intact. This led many clinicians and researchers to recommend IV glutathione or NAC supplementation instead. But the research has evolved considerably.

Standard (Unformulated) Oral Glutathione

A 2015 randomized, double-blind, placebo-controlled study published in the European Journal of Nutrition challenged the long-held assumption that oral glutathione is not bioavailable. The six-month trial, conducted at Penn State University, found that daily supplementation with 250mg or 1,000mg of unformulated oral glutathione significantly increased glutathione levels in blood, buccal cells, and erythrocytes compared to placebo. The higher dose showed greater increases. This study was a turning point, but critics noted that the mechanism — whether intact GSH was absorbed or whether breakdown products were reassembled intracellularly — remained unclear.

Liposomal Glutathione

Liposomal delivery encapsulates glutathione within phospholipid bilayers, protecting it from digestive degradation and enhancing absorption through the intestinal lining. A 2018 pilot study published in the European Journal of Clinical Nutrition found that liposomal glutathione supplementation at doses of 500mg and 1,000mg per day for two weeks significantly increased body stores of glutathione, with the liposomal form showing enhanced biomarkers of immune function including NK cell cytotoxicity. Dr. Rhonda Patrick has referenced this delivery mechanism on FoundMyFitness as a potentially more effective route for oral supplementation.

IV (Intravenous) Glutathione

Intravenous administration bypasses the gut entirely, delivering glutathione directly into the bloodstream. It produces an immediate spike in plasma GSH, but the effect is transient, typically declining within hours. IV glutathione has been investigated in neurological conditions such as Parkinson’s disease, though a 2009 study in Movement Disorders found no significant clinical improvement compared to placebo. The practical limitations — cost ($100-250 per session), frequency requirements, and clinical setting necessity — make IV glutathione impractical for daily supplementation.

NAC (N-Acetylcysteine) as a Precursor Strategy

Rather than supplementing glutathione directly, NAC provides the rate-limiting amino acid cysteine, allowing the body to synthesize glutathione endogenously. NAC has the deepest evidence base of any glutathione-support strategy — used clinically for decades as a mucolytic, as the standard acetaminophen overdose treatment, and as an adjunctive psychiatric therapy. A 2017 systematic review in Redox Biology confirmed that NAC reliably increases intracellular glutathione across multiple human studies. Peter Attia has discussed NAC on The Drive podcast, noting its well-established safety profile.

Glycine + NAC (GlyNAC)

A newer approach combines glycine and NAC, providing two of the three amino acid precursors for glutathione synthesis. The Baylor College of Medicine research group, led by Dr. Rajagopal Sekhar, published a 2021 RCT in Clinical and Translational Medicine showing that GlyNAC supplementation in older adults corrected glutathione deficiency, reduced oxidative stress, improved mitochondrial function, and improved multiple aging hallmarks within 16 weeks.

Liposomal vs Standard Glutathione vs NAC: A Direct Comparison

Answer capsule: Each form of glutathione supplementation carries distinct tradeoffs in absorption, cost, evidence quality, and convenience. Liposomal glutathione offers the best-documented absorption of direct glutathione forms. NAC remains the most evidence-supported and cost-effective precursor strategy. Standard glutathione has emerging evidence but less data than either liposomal or NAC. The right choice depends on your priority — direct GSH elevation versus precursor support.

For a deeper dive, see our complete NAC guide.

Cost estimates are approximate and based on commonly available retail pricing as of March 2026. Actual costs vary by brand, retailer, and quantity purchased.

Glutathione, Liver Support, and Detoxification

Answer capsule: The liver is the body’s primary detoxification organ, and glutathione is its most critical tool. Phase II liver detoxification relies heavily on glutathione conjugation to neutralize drugs, environmental toxins, heavy metals, and metabolic waste products. When hepatic glutathione is depleted — through alcohol, medication use, or chronic toxic exposure — detoxification capacity drops significantly, increasing the risk of liver damage and systemic toxicity.

The liver contains the highest concentration of glutathione of any organ in the body, for good reason. Virtually every toxin that enters the bloodstream passes through the liver, where it undergoes a two-phase detoxification process.

Phase I and Phase II Detoxification

Phase I (functionalization) is carried out by the cytochrome P450 enzyme family, which modifies toxins by adding reactive groups. This actually makes some compounds more reactive and potentially more dangerous — an intermediate step that creates what are sometimes called “activated intermediates.”

Phase II (conjugation) is where glutathione does its primary work. Glutathione S-transferase enzymes attach glutathione molecules to the activated intermediates from Phase I, rendering them water-soluble and non-toxic so they can be excreted through bile or urine. Without adequate glutathione, Phase I products can accumulate and cause cellular damage.

Acetaminophen Metabolism: The Textbook Example

At normal doses, the liver processes acetaminophen through sulfation and glucuronidation. A small fraction is converted by CYP450 enzymes into NAPQI, a highly reactive compound neutralized by glutathione conjugation. In overdose, these primary pathways become saturated, more acetaminophen is shunted through CYP450, and glutathione stores are overwhelmed — causing liver necrosis. The standard emergency treatment is intravenous NAC, which replenishes glutathione. This is one of the most well-validated interventions in emergency medicine.

Alcohol and Glutathione Depletion

Chronic alcohol consumption depletes hepatic glutathione through increased ROS production during ethanol metabolism, direct GSH consumption for acetaldehyde detoxification, and inhibition of synthesis enzymes. Peter Attia has discussed alcohol’s dose-dependent hepatotoxicity on The Drive podcast. Research published in Hepatology has demonstrated that alcoholic liver disease is closely associated with glutathione depletion and that NAC may offer some hepatoprotective benefit, though it is not a substitute for reducing alcohol intake.

Heavy Metals and Environmental Toxins

Glutathione binds directly to heavy metals including mercury, lead, arsenic, and cadmium, facilitating their excretion. Chronic low-level exposure — through contaminated water, seafood, or occupational sources — places ongoing demands on the glutathione system. A 2005 review in Alternative Medicine Review noted that individuals with genetic polymorphisms reducing GST enzyme activity may be more susceptible to heavy metal accumulation.

What the Research Shows: Clinical Evidence for Glutathione Supplementation

Answer capsule: Clinical research on glutathione supplementation has grown substantially over the past decade. Key findings include evidence that both liposomal glutathione and NAC reliably raise blood and intracellular GSH levels, that glutathione status correlates strongly with immune function in older adults, and that precursor supplementation (particularly GlyNAC) improves multiple biomarkers of aging. Limitations remain — large-scale, long-term RCTs are still sparse, and most studies have small sample sizes.

Studies Supporting Supplementation

The Penn State RCT (2015): Published in the European Journal of Nutrition, this six-month RCT found that daily oral glutathione at 250mg and 1,000mg increased blood GSH levels and reduced oxidative stress markers versus placebo. The higher dose also enhanced NK cell cytotoxicity.

Liposomal glutathione pilot (2018): Published in the European Journal of Clinical Nutrition, this study found that liposomal glutathione at 500mg and 1,000mg daily for two weeks increased GSH levels in blood and improved NK cell function. While the sample was small, the results were consistent with the proposed mechanism of liposomal delivery.

The GlyNAC RCT (2021): Published in Clinical and Translational Medicine, this RCT supplemented older adults with glycine and NAC for 16 weeks. Results showed corrected glutathione deficiency, reduced oxidative stress, improved mitochondrial function, reduced inflammation, and improved multiple aging biomarkers. A follow-up study extended these findings.

NAC and immune function (multiple studies): A body of research spanning decades has demonstrated that NAC supplementation supports glutathione levels in immunocompromised populations. A 1997 study in the European Respiratory Journal found that NAC supplementation improved immune cell function in elderly subjects. Research published in Free Radical Biology and Medicine has consistently shown that NAC administration increases intracellular GSH in various cell types.

Limitations and Open Questions

• Sample sizes: Most glutathione supplementation studies involve fewer than 100 participants. Larger trials are needed to confirm findings with statistical robustness.
• Duration: Few studies extend beyond six months. The long-term effects of chronic glutathione supplementation remain poorly characterized.
• Intracellular vs. plasma levels: Blood glutathione levels do not perfectly reflect intracellular levels in tissues. Some researchers argue that plasma GSH measurements overstate the tissue-level impact of supplementation.
• Clinical endpoints: Most studies measure biomarkers (GSH levels, oxidative stress markers) rather than hard clinical endpoints like disease incidence, hospitalization, or mortality. The gap between biomarker improvement and clinical benefit has not been fully bridged.
• Genetic variability: Polymorphisms in GST genes, glutathione synthesis enzymes, and related pathways mean that individual responses to supplementation likely vary significantly. Personalized approaches may ultimately be necessary.
• Cancer context: Concerns exist that exogenous antioxidant supplementation could theoretically protect cancer cells. This remains under investigation, and glutathione supplementation should be discussed with an oncologist in anyone with cancer history.

Promising Research Areas

Neurodegeneration: Glutathione depletion in the substantia nigra is a consistent finding in Parkinson’s disease research. IV glutathione trials have yielded mixed results, but the association between GSH status and neurological health remains under active investigation.

Respiratory health: NAC has been studied in COPD and other respiratory conditions, with some evidence it reduces exacerbation frequency. Its mucolytic properties form the basis of its FDA-approved use.

Aging biomarkers: The GlyNAC research from Baylor is among the most promising — finding that precursor supplementation improved multiple hallmarks of aging simultaneously has generated significant longevity research interest.

For a broader look at how NAD+ pathways connect with antioxidant defense systems, see our guide to David Sinclair’s Longevity Protocol.

Optimal Dosing: What the Evidence Supports

Answer capsule: Dosing depends on the form of supplementation. For liposomal glutathione, research has used 500mg to 1,000mg daily. For NAC as a precursor, 600mg to 1,800mg daily in divided doses is the most commonly studied range. For GlyNAC, the Baylor protocol used approximately 1.2g glycine plus 600mg NAC twice daily. Timing and food intake affect absorption differently depending on the form. These are research-documented doses, not prescriptive recommendations.

Liposomal Glutathione

Standard (Unformulated) Oral Glutathione

NAC (N-Acetylcysteine)

GlyNAC (Glycine + NAC)

Important Dosing Considerations

• Stacking NAC with direct glutathione: Some protocols combine NAC with liposomal glutathione. No published research has evaluated this combination against either alone. Theoretically reasonable but unvalidated.
• Vitamin C co-administration: Some practitioners suggest taking vitamin C alongside glutathione, as vitamin C can help recycle oxidized glutathione. This is mechanistically plausible and low-risk, though not specifically validated in combination trials.
• Who should exercise caution: Individuals on chemotherapy or immunosuppressive medications should discuss glutathione or NAC supplementation with their oncologist or specialist. As noted above, there are theoretical concerns about antioxidant supplementation in the context of certain cancer treatments.

Reminder: These are doses documented in published research, not prescriptive recommendations. Individual needs vary. Consult a healthcare provider before starting glutathione or NAC supplementation, particularly if you take prescription medications.

Best Glutathione Supplements in 2026

Answer capsule: The best glutathione supplement depends on your chosen form — liposomal glutathione for direct GSH with enhanced absorption, standard reduced glutathione for a budget-friendly direct option, or NAC for the most evidence-backed precursor strategy. We evaluate third-party testing, delivery form, dose per serving, and transparent pricing. All products below are available without a prescription.

All affiliate links use rel=”sponsored nofollow” per FTC guidelines. Prices are estimated monthly costs at commonly used doses and may vary by retailer and quantity. Prices current as of March 2026.

How We Evaluate These Products

Third-party testing: Independent COA verifying identity, purity, and absence of contaminants. Setria is a patented form with its own clinical studies. Liposomal products should demonstrate nano-emulsion particle size verification.

Delivery form and evidence: Is the delivery mechanism supported by published research or just marketing? Liposomal delivery has mechanistic and clinical support. Standard capsules have the Penn State RCT. NAC has the deepest evidence base.

Dose transparency: Clear per-serving dose labeling, not hidden behind proprietary blends. Every product on this list provides transparent dosing.

Value: NAC offers the best value per dollar for evidence-supported glutathione repletion. Liposomal glutathione carries a premium partly justified by delivery technology.

For more supplement evaluation methodology and how longevity experts approach stack building, see Andrew Huberman’s Complete Supplement Stack 2026.

The Supplement Nobody’s Heard Of In My Stack

Glutathione is the supplement in my stack that gets the most confused looks when I mention it. Most people haven’t heard of it, and the ones who have usually associate it with IV drips at boutique wellness clinics. I take it as a capsule, and my reasoning is simpler than the IV crowd makes it sound.

Your body produces glutathione naturally — it’s your master antioxidant, involved in detoxification, immune function, and cellular repair. The problem is production declines with age, stress, and environmental exposure. The longevity angle is straightforward: support the system your body already uses to clean up oxidative damage.

I’ll be honest — this is one of the harder supplements to “feel” working. I don’t wake up feeling detoxified. There’s no immediate signal that it’s doing anything. The research on oral glutathione bioavailability has been debated for years, with some studies suggesting liposomal forms absorb better than standard capsules.

So why do I keep taking it? Because it fits into my broader protocol of supporting liver function and reducing oxidative load. It pairs logically with the milk thistle I take at night. The cost is reasonable, the safety profile is clean, and the theoretical basis is sound even if the subjective experience is invisible. Sometimes that’s enough — not every supplement needs to make you feel like a superhero to be earning its place.

I cover the supplements that work quietly and the ones that are all marketing. The CoreStacks Longevity Report — free, weekly.

Keep Reading

• Best glutathione supplements for 2026
• Advanced longevity stacks under $200 featuring glutathione
• Are premium glutathione supplements worth the cost?

Related Comparisons

Looking for more supplement comparisons? Check out our ALA vs NAC comparison.

Frequently Asked Questions About Glutathione

Is NAC better than glutathione supplements?

Neither is categorically “better” — they work through different mechanisms. NAC provides the rate-limiting amino acid cysteine, allowing your body to synthesize glutathione endogenously. Direct glutathione supplements (particularly liposomal forms) deliver the finished molecule. NAC has a deeper evidence base spanning decades of clinical use, is considerably cheaper, and has well-characterized safety data. Direct glutathione supplementation has less clinical history but may benefit individuals whose synthesis capacity is compromised.

Can you take glutathione and NAC together?

There is no published evidence of harmful interactions between direct glutathione and NAC. Some protocols combine both — the rationale being that direct glutathione provides immediate GSH while NAC supports ongoing endogenous production. However, no RCT has evaluated this combination against either alone, so the additive benefit is assumed rather than demonstrated.

What depletes glutathione the fastest?

Acetaminophen (Tylenol) overdose is the most dramatic single-event depleter, which is why NAC is the standard emergency treatment. For chronic depletion, heavy alcohol consumption, environmental toxins, severe stress, and aging itself are the primary drivers. Protein-deficient diets — particularly those low in cysteine and glycine — limit glutathione synthesis.

Should I take glutathione on an empty stomach?

For liposomal glutathione, an empty stomach is generally recommended to optimize absorption without competition from food. For NAC, taking it away from meals is typically suggested, though NAC on an empty stomach causes GI discomfort in some people — taking it with a small amount of food is a reasonable compromise. The Penn State study did not strictly control meal timing, so evidence for food timing with standard glutathione is less clear.

How long does it take for glutathione supplements to work?

Blood glutathione levels can increase within days to weeks with liposomal glutathione, based on the 2018 pilot study. NAC raises intracellular GSH over several weeks. The GlyNAC protocol showed measurable improvements at 16 weeks. If tracking through lab work, expect at least 4–8 weeks of consistent supplementation before retesting.

Is glutathione safe long-term?

NAC has the longest safety track record, having been used clinically for decades with a well-characterized side effect profile (primarily GI discomfort at higher doses). The Penn State study evaluated standard oral glutathione over six months without significant adverse events. Long-term data beyond one year is limited. Individuals with active malignancies or on chemotherapy should consult their oncologist, as the theoretical concern about antioxidant supplementation supporting cancer cells remains an open question.

Does glutathione lighten skin?

Glutathione has been marketed for skin lightening, particularly in Southeast Asia. A 2017 study in the Journal of Cosmetic Dermatology reported some effects over 12 weeks, but the evidence base is thin, and dermatological organizations in several countries have raised safety concerns about high-dose IV glutathione for cosmetic purposes. This is not a longevity-related application.

What foods are high in glutathione?

Foods that contain glutathione or support its production include cruciferous vegetables (broccoli, Brussels sprouts, cauliflower, kale), allium vegetables (garlic, onions), avocados, asparagus, spinach, and whey protein (which provides cysteine). However, dietary glutathione faces the same digestive breakdown concerns as standard supplements. The more important dietary strategy is adequate protein intake to supply cysteine, glycine, and glutamate for endogenous synthesis. Dr. Rhonda Patrick has discussed the role of sulforaphane from broccoli sprouts in upregulating the Nrf2 pathway, which activates glutathione synthesis.

Medical Disclaimer: CoreStacks reports on published research and publicly shared expert opinions. We do not make health claims, diagnose conditions, or recommend specific supplements or dosages. Glutathione and NAC are available as dietary supplements, but the FDA has not approved them for the treatment, cure, or prevention of any disease. Individual responses to supplementation vary. Always consult a qualified healthcare provider before starting, stopping, or modifying any supplement regimen, especially if you are pregnant, nursing, taking prescription medications, or have an existing health condition. Nothing in this article constitutes medical advice.

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