Oxidative Stress Biomarkers: NAD+ and Glutathione Roles

Explore how NAD+ and Glutathione biomarkers reveal insights into oxidative stress, metabolism, and strategies for enhancing cellular health.

Medically reviewed by Dr. Ruth Cohen,
Medical Director, Layla
Reviewed by
Dr. Ruth Cohen
Medical Director, Layla
Last Updated
February 25, 2025
8 clinical references

Oxidative Stress Biomarkers: NAD+ and Glutathione Roles

Oxidative stress, linked to aging and chronic diseases, can be tracked using NAD+ and Glutathione biomarkers. These molecules reveal energy production, antioxidant capacity, and cellular health. Key takeaways:

  • NAD+: Supports metabolism, energy production, and redox balance. Levels drop with age, impacting health.
  • Glutathione: The body's main antioxidant, protects against oxidative damage and supports detoxification.

Maintaining or boosting these biomarkers through supplements, diet, and lifestyle changes can improve metabolic and cellular health. Treatments like NAD+ injections and glutathione supplementation are now accessible via telehealth platforms.

How NAD Enhances Glutathione

NAD+ Functions in Cell Health

NAD⁺ plays a central role in keeping cells healthy by supporting energy production and managing oxidative stress. It’s involved in several enzymatic reactions critical for these processes [2].

How NAD⁺ Supports Metabolism

NAD⁺ is essential for energy production in cells, serving as a cofactor for enzymes in key metabolic pathways like:

  • Glycolysis
  • The tricarboxylic acid (TCA) cycle
  • β-oxidation of fatty acids [2]

It works by accepting hydride ions to form NADH, which powers redox reactions in both the cytosol and mitochondria. Around 10% of NAD⁺ is converted into NADP⁺, which then reduces to NADPH. NADPH is especially important for processes like fatty acid and cholesterol synthesis [2].

NAD⁺ Levels and Aging

Studies have shown that NAD⁺ levels drop significantly as we age, impacting various biological systems. Here’s a breakdown of what happens:

Mechanism Impact
Reduced NAMPT-mediated NAD⁺ production Lower energy availability in cells
Increased NAD⁺ consumption by PARP enzymes Depletion of NAD⁺ reserves
Greater breakdown of NAD⁺ by CD38 Impaired cellular functions

For example, older adults typically have about one-third less intramuscular NAD⁺ compared to younger individuals [4]. This decline not only reduces energy production but also makes cells more susceptible to oxidative stress, which can contribute to conditions like cardiovascular and neurodegenerative diseases [3].

NAD⁺ Supplementation and Potential Benefits

Research highlights the potential of NAD⁺ supplementation to address age-related declines. In one study, heart failure patients took 2000 mg of nicotinamide riboside (NR) daily for 5–9 days. Results showed:

  • Higher whole blood NAD⁺ levels
  • Improved basal and maximal respiration in blood cells
  • Significant reductions in inflammation markers [2]

Animal studies have also shown that long-term nicotinamide mononucleotide (NMN) supplementation can improve energy metabolism, boost physical activity, and even reverse some age-related changes in gene expression [3].

sbb-itb-b172b91

Glutathione's Antioxidant Effects

Glutathione Properties

Glutathione (GSH) is a small molecule made up of glutamate, cysteine, and glycine, and it's the body's main intracellular antioxidant. Found in every cell, it's especially abundant in the liver, where concentrations can reach up to 10 mM, compared to a general tissue range of 0.1 to 10 mM [5]. One of its key features is its ability to switch between a reduced form (GSH) and an oxidized form (GSSG). This balance between GSH and GSSG is a useful marker of cellular redox status. Here are typical values for healthy adults:

Parameter Normal Range
Reduced GSH 486 ± 85 mmol/L
Oxidized GSSG 68 ± 26 mmol/L
Total Glutathione 553 ± 90 mmol/L
GSH/GSSG Ratio 8.1 ± 2.7

These measurements help assess the balance of oxidative and reductive processes in cells.

Glutathione's Impact on Metabolism

Glutathione plays a major role in protecting metabolism. Over 95% of it exists in its reduced, active form, where it neutralizes reactive oxygen species (ROS). Its key metabolic roles include:

  • Mitochondrial Protection: Shields mitochondria during periods of high energy demand.
  • Detoxification: Assists in removing toxins from the body.
  • Immune System Support: Regulates immune activity and helps produce inflammatory mediators.
  • Vitamin Metabolism: Influences the processing of vitamins D, E, and C [6].

Low glutathione levels are associated with oxidative stress and inflammation, which can lead to metabolic disorders. For instance, a study by Rani et al. [6] found that diabetic patients who took N-acetylcysteine supplements for six months saw improvements in HbA1C, blood pressure, C-reactive protein, triglycerides, and HDL cholesterol.

Increasing Glutathione Naturally

Keeping glutathione levels in check is crucial for metabolic health. Here are a few ways to naturally support its levels:

  • Vitamin C Supplementation
    Research shows that taking 500–1,000 mg of vitamin C daily for 13 weeks can raise white blood cell glutathione by 18%. A daily dose of 500 mg has been shown to increase red blood cell glutathione by 47% [7].

  • Eating Glutathione-Rich Foods
    Certain foods are naturally high in glutathione and can help maintain its levels:

    Food Glutathione Content (μg/g)
    Asparagus 349 ± 26
    Avocado 339 ± 10
    Spinach 313 ± 33
    Green Beans 230 ± 2
  • Lifestyle Adjustments
    Regular cardio and circuit training have been shown to boost glutathione levels. Maintaining a consistent sleep schedule and limiting alcohol intake are also important. Excessive alcohol consumption can reduce lung glutathione by as much as 80–90% [7].

Treatment Options and Services

With growing evidence supporting their role in cellular metabolism and antioxidant defense, NAD+ and Glutathione treatments are now available through telehealth services.

Online Health Services

Telehealth platforms make accessing NAD+ and Glutathione treatments easier than ever. Through virtual consultations and home delivery, patients can now receive these therapies without visiting a clinic [10]. For instance, Join Layla offers these treatments via licensed providers, creating personalized plans and providing continuous clinical support - all online.

Another option, Heally, provides NAD+ injection programs. They start with a free consultation and operate on a subscription model priced at $249 per month, which includes medication delivered directly to your home [8].

"The NAD+ injection gave me a noticeable boost in energy. I feel more focused and productive throughout the day." - Sarah T., 42 years old [8]

These services are changing how patients access and maintain treatment plans, offering convenience and flexibility.

Treatment Combinations

Beyond individual therapies, combining treatments like NAD+ and Glutathione can amplify metabolic support. For example, pairing these treatments enhances the body’s ability to manage oxidative stress. Research on HIV-infected males demonstrated that a 14-day cysteine (0.81 mmol/kg/d) and glycine (1.33 mmol/kg/d) protocol significantly improved glutathione synthesis:

Parameter Improvement
Glutathione Fractional Synthesis Rate 120% increase
Absolute Synthesis Rate 230% increase
RBC Glutathione Concentration 53% increase

NAD+ treatments have also been studied for safety. A 2019 study involving healthy males aged 30–55 showed that a 6-hour IV infusion of NAD+ caused no adverse effects. While some changes in liver function markers were noted, they were not considered clinically concerning [9].

"Telehealth has become such an important part of medical care. It has really increased access to the patients who need it the most." [10]

For those considering combined treatments, working with qualified healthcare providers is key. They can monitor progress and make adjustments as needed. Modern telehealth platforms simplify this process by enabling regular communication, helping patients stick to their treatment plans and achieve better outcomes.

Summary and Future Outlook

Main Points

NAD+ and Glutathione are key indicators of oxidative stress. The NAD+/NADH ratio reflects the body's metabolic redox balance [1]. Intranasal NAD+ delivery has shown promise, reducing infarct formation by about 85% in rat studies, highlighting its potential in addressing oxidative stress [11]. Research also shows that declining NAD+ levels are linked to biological dysfunction and age-related diseases [1], prompting therapeutic efforts for issues like glaucoma and macular degeneration [13].

Building on these discoveries, ongoing studies aim to refine and improve these treatments.

Future Developments

These findings open doors to new treatment approaches. For example, research on Ndufs4-KO mice revealed that NMN supplementation doubled median lifespan by correcting NAD+ redox imbalances [12].

"It is increasingly likely that future studies on NAD- and NADP-dependent enzymes, such as NADPH oxidase, PARP-1, and sirtuins, would expose novel mechanisms underlying the roles of oxidative stress in cerebral ischemia, and suggest new therapeutic strategies for treating the debilitating disease" [11].

Additionally, combining NAD+ metabolism targeting with hypoxia signaling could improve therapies for mitochondrial disorders [12]. Safer, more accessible options like NAD+ precursors used as nutraceuticals have shown good tolerability in humans [12].

These advancements aim to make metabolic treatments more effective and widely applicable in clinical settings.

Tirzepatide: The New Challenger
Tirzepatide is relatively new to the market and works by activating both the GLP-1 and GIP receptors. This dual-action approach is theorized to offer more potent effects on weight loss and glucose control.
Advantages:
Early studies indicate that Tirzepatide may offer superior glucose-lowering effects and weight loss compared to GLP-1 agonists alone. The medication could potentially provide an improvement in treatment outcomes for individuals with type 2 diabetes, particularly those who are also focusing on weight loss as part of their treatment goals.
Considerations:
As a newer medication, Tirzepatide’s long-term safety profile is still being established. Patients may experience side effects similar to other medications in the GLP-1 class, and close monitoring by a healthcare provider is recommended.
Choosing the Right GLP-1 Medication with Layla
At Layla, we provide a comprehensive overview of the GLP-1 medication options available in our program, detailing the benefits and considerations of each to help you make an informed decision for diabetes management or weight loss.
Semaglutide
A widely chosen GLP-1 medication, Semaglutide boasts a high satisfaction rate among patients due to its convenience of once-weekly dosing and efficacy in reducing blood sugar levels and aiding weight loss. When selecting Semaglutide through Layla, consider how its dosing schedule and health benefits align with your lifestyle.
What makes Semaglutide a highly effective choice?
Caret

Acts on biological factors that can prevent weight loss
Suppresses appetite & helps you feel fuller, longer
Helps control blood sugars

Can I feel confident in the safety of Semaglutide?
Caret

3 MONTH STARTER PROGRAM
● Best value option
● Ideal for those commencing their weight loss journey
● Convenient billing method: $247 charged monthly
● Doses start at 0.25 mg/week, escalating to 2.5 mg/week (totaling 10 mg)
● Limited to one use per customer

MONTHLY PROGRAM
● $297 per month
● Available for customers starting at a higher dose or already on medication

How does the program work?
Caret

STEP 1: Place your order online and complete a medical intake form detailing your health and weight loss goals.

STEP 2: Connect with your physician through our HIPAA-compliant telehealth platform. No more waiting weeks or months for appointments.

STEP 3: Once approved, your prescription is sent to a pharmacy, which will deliver the medication straight to your door.

STEP 4: Ongoing Support. We regularly check in with you to ensure you're maximizing the benefits of our program. Our support team is available for chat, and you can message your doctor anytime with questions.

See available plans
Tirzepatide
Tirzepatide stands as a powerful GLP-1 medication alternative, particularly for those seeking an effective diabetes and weight management solution with a more spaced dosing regimen. Its administration through injections allows for flexible treatment planning tailored to individual needs.
What makes Tirzepatide a highly effective choice?
Caret

Acts on biological factors that can prevent weight loss
Suppresses appetite & helps you feel fuller, longer
Helps control blood sugars

Can I feel confident in the safety of Tirzepatide?
Caret

3 MONTH STARTER PROGRAM
● Best value option
● Ideal for those commencing their weight loss journey
● Convenient billing method: $247 charged monthly
● Doses start at 0.25 mg/week, escalating to 2.5 mg/week (totaling 10 mg)
● Limited to one use per customer

MONTHLY PROGRAM
● $297 per month
● Available for customers starting at a higher dose or already on medication

How does the program work?
Caret

STEP 1: Place your order online and complete a medical intake form detailing your health and weight loss goals.

STEP 2: Connect with your physician through our HIPAA-compliant telehealth platform. No more waiting weeks or months for appointments.

STEP 3: Once approved, your prescription is sent to a pharmacy, which will deliver the medication straight to your door.

STEP 4: Ongoing Support. We regularly check in with you to ensure you're maximizing the benefits of our program. Our support team is available for chat, and you can message your doctor anytime with questions.

See available plans

Unsure about the right treatment?

Our team can help. Answer a few quick questions about yourself, and we'll guide you to the most suitable treatment option.