Why Fixing Inflammation Matters More Than Supplementing NADH and CoQ10

How Holistic Lifestyle Practices Restore Your Body’s Natural Energy System Through Redox Balance and Mitochondrial Integrity

By Brian S.

Supplements like NADH and CoQ10 promise energy, but without fixing chronic inflammation and oxidative stress, they may be ineffective. Learn how holistic lifestyle practices optimize mitochondrial function at the cellular level.

An abstract depiction of the human body's inner energy flow, where inflammation and oxidative stress (red and orange) are counterbalanced by healing forces (green and blue) from holistic lifestyle practices. Glowing molecular structures represent NADH and CoQ10 restoring mitochondrial vitality and cellular balance. 

Introduction

Many people turn to NADH and Coenzyme Q10 (CoQ10) supplements in hopes of improving energy, brain health, or reversing fatigue. While these coenzymes are indeed crucial for cellular energy metabolism, their effectiveness largely depends on how well the body regulates oxidative stress and inflammation — not simply on how much is consumed.

A deeper look into molecular biology and fundamental physiology reveals why restoring redox balance and mitochondrial resilience is a more effective and lasting strategy than supplementation alone.  Chronic Inflammation and Oxidative Stress Disrupt NADH & CoQ10 Utilization

Inflammation Interferes with Mitochondrial Function

Inflammation upregulates enzymes such as inducible nitric oxide synthase (iNOS) and NADPH oxidase, which flood the cell with reactive oxygen species (ROS). These ROS not only damage DNA and lipids but also impair the redox cycling of NADH and CoQ10, essential cofactors in mitochondrial respiration (Forrester et al., 2018).

NADH, which donates electrons to Complex I of the electron transport chain (ETC), becomes less effective when inflammation hampers NAD⁺ regeneration or when oxidative damage impairs mitochondrial enzymes (Canto et al., 2015). Likewise, CoQ10 — the electron shuttle between Complexes I/II and III — is highly susceptible to oxidative inactivation (Crane, 2001).

The Result: Energy Crisis at the Molecular Level

• Inhibited ATP production
• Accumulation of partially reduced intermediates
• Heightened mitochondrial dysfunction and fatigue

This forms a vicious cycle: inflammation increases ROS, which in turn worsens mitochondrial dysfunction — further amplifying fatigue, aging, and disease progression. 

Why Supplementation May Be Insufficient

While NADH and CoQ10 supplements offer transient benefits, especially in clinical mitochondrial disorders or aging-related decline, they do not address the root cause — redox imbalance and chronic metabolic stress.

Studies show that oral NADH has limited absorption, and its efficacy is contingent on redox homeostasis and mitochondrial capacity to use it (Pfeiffer et al., 1995). Similarly, exogenous CoQ10 must undergo enzymatic reduction to ubiquinol before entering the mitochondrial chain — a process easily disrupted by oxidative stress (Littarru & Tiano, 2007).   

Restore First, Supplement Second: The Holistic Physiology Approach

Rather than defaulting to supplements, prioritizing holistic lifestyle strategies that enhance the body’s natural regulation of NADH and CoQ10 is more sustainable and rooted in core physiology. 

Key Practices and Their Molecular Benefits:

Lifestyle Practice	Molecular Mechanism
Anti-inflammatory diet (e.g., Mediterranean)	Suppresses NF-κB, reduces iNOS, lowers mitochondrial oxidative burden (Calder, 2017)
Intermittent fasting	Activates SIRT1 and AMPK → enhances NAD⁺ recycling, promotes mitochondrial biogenesis (Brandhorst et al., 2015)
Moderate exercise	Induces PGC-1α → increases endogenous CoQ10/NADH generation and mitochondrial density (Safdar et al., 2011)
Circadian rhythm regulation	Synchronizes NAD⁺ biosynthesis and cellular respiration with daylight cycles (Peek et al., 2013)
Stress management	Reduces cortisol and sympathetic overdrive, minimizing redox disturbance
Phytonutrient intake (e.g., resveratrol, curcumin)	Activates Nrf2 → enhances endogenous antioxidant enzymes (Li et al., 2019)

Molecular Perspective: NADH and CoQ10 as Internal Regulators, Not External Band-Aids

These cofactors should be seen not as external fixes but as internal regulators, deeply intertwined with:

• Cellular redox signaling
• Epigenetic regulation
• Mitochondrial biogenesis

If the cell is in a pro-inflammatory, oxidized state, even high doses of CoQ10 or NADH cannot rescue function effectively (Ghosh et al., 2020). What is needed is a systemic restoration of the redox environment, allowing endogenous synthesis, recycling, and function to flourish.  

Conclusion: Reinforce Physiology First

In summary, NADH and CoQ10 are biological agents, not magic bullets. Their true potential is unlocked only when the cellular environment is prepared — through lifestyle, not shortcuts.

“Fixing inflammation and oxidative stress is not optional. It is the biological prerequisite for restoring the natural rhythm and function of NADH and CoQ10.”

Instead of asking, “What should I take?”, begin asking:
“What conditions must I restore in my body so that it makes and uses what it already knows how to produce?” 

References 

Brandhorst, S., Choi, I.Y., Wei, M., et al. (2015). 'A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan.' Cell Metabolism, 22(1), pp.86–99.

Calder, P.C. (2017). 'Omega-3 fatty acids and inflammatory processes: from molecules to man.' Biochemical Society Transactions, 45(5), pp.1105–1115.

Cantó, C., Menzies, K.J. and Auwerx, J. (2015). 'NAD⁺ metabolism and the control of energy homeostasis: a balancing act between mitochondria and the nucleus.' Cell Metabolism, 22(1), pp.31–53.

Crane, F.L. (2001). 'Biochemical functions of coenzyme Q10.' Journal of the American College of Nutrition, 20(6), pp.591–598.

Forrester, S.J., Kikuchi, D.S., Hernandes, M.S., Xu, Q. and Griendling, K.K. (2018). 'Reactive oxygen species in metabolic and inflammatory signaling.' Circulation Research, 122(6), pp.877–902.

Ghosh, S., Castillo, E., Frias, E. and Swanson, R.A. (2020). 'Oxidative stress and mitochondrial dysfunction in Alzheimer’s disease.' Neurobiology of Disease, 145, p.105–108.

Li, W., Khor, T.O., Xu, C. and Kong, A.N. (2019). 'Activation of Nrf2-antioxidant signaling pathway by chemopreventive agents: oxidative stress as a major inducer.' Antioxidants & Redox Signaling, 11(6), pp.1233–1266.

Littarru, G.P. and Tiano, L. (2007). 'Bioenergetic and antioxidant properties of coenzyme Q10: recent developments.' Molecular Biotechnology, 37(1), pp.31–37.

Peek, C.B., Affinati, A.H., Ramsey, K.M., et al. (2013). 'Circadian clock NAD⁺ cycle drives mitochondrial oxidative metabolism in mice.' Science, 342(6158), p.1243417.

Pfeiffer, C.C., Jenney, E.H., Goldstein, L. and McGinnis, W.R. (1995). 'NADH clinical improvement in Parkinson patients.' Biomedical Therapy, 13(1), pp.27–30.

Safdar, A., Little, J.P., Stokl, A.J., et al. (2011). 'Exercise increases mitochondrial PGC-1α content and promotes nuclearly encoded mitochondrial gene expression in human skeletal muscle.' Applied Physiology, Nutrition, and Metabolism, 36(5), pp.598–607.

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Curcumin and Liver Health: Is Piperine-Enhanced Curcumin Putting You at Risk?

Exploring the Safety of High-Bioavailability Curcumin Supplements Versus Traditional Turmeric Use

BY BRIAN S.

Curcumin is hailed for its anti-inflammatory benefits, but can piperine-enhanced supplements cause liver toxicity? Discover the science behind turmeric, bioavailability, and hepatotoxicity risk.

Turmeric (Curcuma longa) has been revered in traditional medicine for centuries, especially in systems such as Ayurveda and Jamu. Its main active component, curcumin, is known for potent anti-inflammatory and antioxidant properties. However, the modern supplement industry has isolated curcumin and combined it with piperine (from black pepper) to improve its notoriously low bioavailability. While this may seem like a win for effectiveness, emerging evidence suggests it could come with unintended risks—including hepatotoxicity.

The Hepatotoxicity Issue: Real but Reversible

A number of recent case reports have shown that some individuals develop drug-induced liver injury (DILI) from high-dose curcumin supplementation, especially when taken with piperine. Symptoms often include jaundice, elevated liver enzymes, and fatigue, but fortunately, these effects appear to be reversible upon discontinuation of the supplement.

For example, Lukefahr et al. (2020) reviewed several cases of liver injury linked to curcumin-piperine combinations. These individuals had no prior liver disease and recovered fully after stopping supplementation.

The Role of Piperine in Liver Toxicity

Piperine plays a double-edged role. While it enhances curcumin absorption by up to 2000% (Shoba et al., 1998), it does so by inhibiting key liver enzymes, namely CYP3A4 and UGT (UDP-glucuronosyltransferase). These enzymes are critical for metabolizing curcumin and detoxifying many drugs. By blocking them, piperine can cause curcumin (and possibly other substances) to accumulate in the liver, potentially leading to oxidative stress and toxicity.

This becomes particularly concerning when curcumin is consumed in doses far exceeding traditional dietary intake.

🌿 Whole Turmeric: A Safer, Synergistic Alternative?

Contrast this with whole turmeric powder, which contains not only curcuminoids but also essential oils, polysaccharides, and natural compounds that may buffer and balance curcumin’s effects. Traditional use of turmeric in diets—up to 1 teaspoon three times daily over years—has not been associated with jaundice or liver dysfunction in anecdotal or ethnomedical records.

This underscores a key principle: whole herbs often operate within a safety buffer that isolated compounds do not.

⚖️ A Comparative Look: Whole Turmeric vs. Curcumin Supplement

Feature	Whole Turmeric	Curcumin + Piperine
Bioavailability	Low	Very high
Synergistic compounds	Present	Lacking
Safety record	Long-term, favorable	Limited, concerns exist
Mechanism	Holistic, food-like	Drug-like, potent
Liver risk	Very low	Moderate (idiosyncratic)

💊 Curcumin: Food or Drug?

Curcumin in piperine-enhanced form behaves pharmacologically like a modern drug, bypassing many of the body’s natural metabolic checkpoints. While this may be ideal for acute inflammation or targeted therapeutic use, it also increases the risk of liver burden, particularly in people with pre-existing liver conditions, genetic variations in CYP450 enzymes, or those on multiple medications.

In essence, when curcumin is taken in isolation and concentrated form, we are no longer dealing with food, but with a powerful bioactive substance—one that needs to be treated with the same caution as pharmaceuticals.

✅ Conclusion: Therapeutic Wisdom from Nature

While high-bioavailability curcumin may have its place in short-term therapy, it is crucial to respect the boundaries of traditional herbal wisdom. Whole turmeric—used with food or in simple teas—offers a safer long-term strategy with a more favorable safety profile.

If choosing a supplement, opt for formulations without piperine, or those that use phospholipid-based delivery systems (like Meriva®) which may offer enhanced absorption without enzyme inhibition.

As modern science continues to validate ancient remedies, it also reminds us: more is not always better—especially when nature has already provided a safe template for healing.

📚 References

Lukefahr, A. L., McGill, M. R., Tandri, H. and Bourgeois, J. A., 2020. Hepatotoxicity associated with curcumin supplementation: A systematic review and meta-analysis. The American Journal of Medicine, 133(11), pp.1388–1393.

Nelson, K. M., Dahlin, J. L., Bisson, J., Graham, J., Pauli, G. F. and Walters, M. A., 2017. The essential medicinal chemistry of curcumin. Journal of Medicinal Chemistry, 60(5), pp.1620–1637.

Shoba, G., Joy, D., Joseph, T., Majeed, M., Rajendran, R. and Srinivas, P. S., 1998. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Medica, 64(4), pp.353–356.

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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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