Endogenous Antioxidants and Aging: Why Glutathione, CoQ10, and ALA Decline—and How to Restore Them

Discover how aging, chronic illness, and stress deplete natural antioxidants—and how holistic strategies can restore balance

By Brian S.

Learn why key antioxidants like glutathione, alpha-lipoic acid, and CoQ10 decline with age. Explore holistic and lifestyle practices to restore antioxidant levels and promote healthy aging.

Why Elder Individuals Lack Key Endogenous Antioxidants: Glutathione, Alpha-Lipoic Acid, and Coenzyme Q10

The human body is equipped with its own antioxidant defense system, producing vital compounds like glutathione, alpha-lipoic acid (ALA), and coenzyme Q10 (CoQ10). These substances neutralize oxidative stress and protect cellular health. However, aging and certain chronic conditions can significantly reduce their levels, leading to increased vulnerability to inflammation, fatigue, and disease.

The Role of Endogenous Antioxidants

Antioxidant	Nature	Primary Functions
Glutathione	Water-soluble	Detoxification, immune support, redox balance
Alpha-Lipoic Acid (ALA)	Water- & lipid-soluble	Regenerates other antioxidants; mitochondrial cofactor
Coenzyme Q10 (CoQ10)	Lipid-soluble	Cellular energy (ATP) production; membrane antioxidant

These antioxidants are synthesized endogenously but require sufficient nutrients and a functioning metabolic system.

Why Levels Decline with Age

1. Inflammaging

"Inflammaging" refers to chronic, low-grade inflammation that arises with aging. This persistent inflammation increases reactive oxygen species (ROS), contributing to the depletion of endogenous antioxidants (Franceschi et al., 2000).

2. Chronic Diseases

• Diabetes increases oxidative stress via glycation end-products and mitochondrial dysfunction (Baynes, 1991).
• Hypertension disrupts redox balance, promoting vascular oxidative stress (Rodrigo et al., 2011).

These conditions deplete glutathione and CoQ10 more rapidly and hinder ALA’s mitochondrial role.

3. Chronic Psychological Stress

Stress elevates cortisol, which has been shown to suppress antioxidant enzyme systems, including glutathione peroxidase (McIntosh et al., 1998).

4. Polypharmacy

Medications such as statins lower CoQ10 synthesis (Gugliucci, 2005), while acetaminophen depletes glutathione reserves. Multiple drugs increase oxidative burden on the liver.

5. Nutrient Deficiencies

Key micronutrients like selenium, B-complex vitamins, magnesium, and amino acids (e.g., cysteine, glycine) are precursors for glutathione and CoQ10 synthesis. Deficiencies impair production (Wu et al., 2004).

Protective Strategies for Healthy Aging

1. Balanced Nutrition

Include a wide variety of vegetables and fruits rich in antioxidants, such as berries, leafy greens, citrus fruits, and cruciferous vegetables. Sulfur-containing foods like garlic and onions also support the body’s production of glutathione.

2. Avoid Toxin Accumulation

Prevent constipation, minimize consumption of deep-fried foods, reduce added sugar intake, and avoid habitual overeating—all of which contribute to oxidative stress and chronic inflammation.

3. Physical Activity

Engage in moderate, regular exercise to enhance the activity of endogenous antioxidant enzymes and support mitochondrial health (Radak et al., 2008).

4. Ample, Quality Sleep

Sufficient restorative sleep promotes mitochondrial repair and boosts melatonin, a potent antioxidant involved in circadian regulation.

5. Stress Management

Practices such as mindfulness, meditation, prayer, and meaningful social connections help reduce chronic cortisol elevation and systemic inflammation.

6. Consult Holistic Health Practitioners

In conjunction with a healthy lifestyle, consulting experienced holistic health and preventive medicine practitioners may provide additional support. They may recommend specific herbal combinations that exhibit antioxidant, anti-inflammatory, detoxifying, cytoprotective, and neuroprotective properties, offering integrative benefits for healthy aging.

Conclusion

Glutathione, alpha-lipoic acid, and CoQ10 are critical endogenous antioxidants that decline with age, especially in the presence of stress, chronic disease, and poor lifestyle habits. However, this decline is not irreversible. Through informed lifestyle practices, nutrient-dense diets, and the guidance of holistic practitioners, individuals can preserve and even restore their antioxidant defenses, promoting longevity and resilience against age-related diseases.

References

Baynes, J. W. (1991). Role of oxidative stress in development of complications in diabetes. Diabetes, 40(4), 405–412.

Franceschi, C., Bonafè, M. & Valensin, S. (2000). Inflamm-aging: an evolutionary perspective on immunosenescence. Annals of the New York Academy of Sciences, 908(1), 244–254.

Gugliucci, A. (2005). Statins, oxidative stress and the endothelium: a new pharmacological tool for cardiovascular disease prevention. Current Drug Targets - Cardiovascular & Hematological Disorders, 5(2), 133–140.

McIntosh, L. J., Hong, K. E., & Sapolsky, R. M. (1998). Glucocorticoids may alter antioxidant enzyme capacity in the brain: baseline studies. Journal of Neurochemistry, 70(1), 208–215.

Radak, Z., Chung, H. Y., & Goto, S. (2008). Systemic adaptation to oxidative challenge induced by regular exercise. Free Radical Biology and Medicine, 44(2), 153–159.

Rodrigo, R., Gonzalez, J., & Paoletto, F. (2011). The role of oxidative stress in the pathophysiology of hypertension. Hypertension Research, 34, 431–440.

Wu, G., Y. Z., Yang, S., Lupton, J. R., & Turner, N. D. (2004). Glutathione metabolism and its implications for health. The Journal of Nutrition, 134(3), 489–492.

Footnote:

While alpha-lipoic acid (ALA) and coenzyme Q10 (CoQ10) are valuable endogenous antioxidants and mitochondrial cofactors, their supplementation may provide minimal benefit in the absence of supportive lifestyle factors. Chronic inflammation, poor diet, oxidative stress, and impaired mitochondrial function reduce the body’s ability to utilize these compounds effectively. ALA, for example, requires the presence of other antioxidants like vitamins C and E to regenerate them (Packer et al., 1997), while CoQ10's role in ATP synthesis depends on intact mitochondrial machinery (Littarru & Tiano, 2007). Moreover, studies suggest that the clinical benefits of these supplements are enhanced when combined with lifestyle modifications such as exercise, antioxidant-rich diets, and stress reduction (Higgins et al., 2020). Without such a foundation—or supportive herbal strategies (e.g., adaptogens, detoxifiers)—the impact of supplementation is likely to be limited.

References:

• Higgins, J.P., Babu, K.M., Deuster, P.A. & Shearer, J. (2020). Coenzyme Q10 supplementation and exercise performance: a systematic review. Journal of Strength and Conditioning Research, 34(2), pp. 470–481.
• Littarru, G.P. & Tiano, L. (2007). Bioenergetic and antioxidant properties of coenzyme Q10: recent developments. Molecular Biotechnology, 37(1), pp. 31–37.
• Packer, L., Witt, E.H. & Tritschler, H.J. (1997). Alpha-lipoic acid as a biological antioxidant. Free Radical Biology and Medicine, 19(2), pp. 227–250.

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