Your High-Dose Vitamin C and E Might Be Sabotaging Endurance Gains

You finish a hard interval session, legs burning, lungs screaming. You reach for your recovery stack: protein, electrolytes, and your daily antioxidant capsules loaded with vitamin C and E. It's a ritual repeated in training rooms and kitchens across the endurance world. The logic seems airtight. Exercise creates oxidative stress. Antioxidants neutralize oxidative stress. Therefore, antioxidants protect your muscles and accelerate adaptation.

But what if that logic, while chemically sound, misses something fundamental about how the human body responds to training?

What's rarely discussed in supplement marketing is whether aggressively reducing oxidative stress during training might also silence the very signals that tell your body to adapt in the first place. A controlled human trial examined this question directly by tracking both performance and the molecular responses inside skeletal muscle during an 11-week endurance program. The results challenge the simplistic view that antioxidants are always beneficial for athletes.

The Research Question: Protection or Interference?

The investigators designed a study with a specific and narrow focus. They wanted to determine whether daily supplementation with 1000 mg of vitamin C and 235 mg of vitamin E would alter physiological adaptations to a structured endurance training program in humans.

This wasn't about acute recovery from a single workout or whether antioxidants reduce muscle soreness. The question was deeper: does chronic antioxidant use affect how skeletal muscle responds at a cellular level to repeated endurance exercise over time?

Critical Distinction: This study examined training adaptations, not just performance outcomes. The researchers looked inside muscle tissue to measure the molecular machinery that underpins long-term endurance capacity.

Study Design: Separating Signal From Noise

The trial employed a double-blind, randomized, placebo-controlled design, the gold standard for minimizing bias in supplementation research. Neither participants nor researchers knew who received supplements or placebo until data analysis was complete.

Who Was Studied

A total of 54 healthy young men and women were recruited. All participants were free from known disease and capable of completing a structured endurance training program. The inclusion of both sexes improves generalizability compared with single-sex studies, though the researchers didn't report separate analyses for men and women.

The Supplementation Protocol

Participants were randomly assigned to one of two groups for the full 11-week training period:

Group	Daily Supplementation	Notes
Antioxidant Group	1000 mg Vitamin C + 235 mg Vitamin E	High doses reflecting common supplement formulations
Placebo Group	Matched placebo capsules	Identical appearance, no active ingredients

The doses used were intentionally high and reflect amounts commonly found in over-the-counter antioxidant supplements marketed to athletes. This wasn't about dietary intake from food. It was about supplementation behavior that occurs in the real world.

The Training Program: Real Endurance Stress

All participants followed the same endurance training plan designed to create a strong stimulus for cardiovascular and mitochondrial adaptation:

• Frequency: 3 to 4 sessions per week
• Mode: Running-based endurance training
• High-intensity intervals: 4 to 6 repetitions of 4 to 6 minutes at greater than 90 percent of maximum heart rate
• Continuous running: 30 to 60 minutes at 70 to 90 percent of maximum heart rate

This combination of intensity and volume represents the kind of training that drives meaningful endurance adaptations. It's not beginner-level exercise. It's the type of program that creates metabolic stress and forces the body to upgrade its aerobic machinery.

What They Measured: Surface and Substrate

Measurements were taken before and after the 11-week intervention, examining both what athletes care about (performance) and what physiologists care about (cellular adaptations).

Performance and physiological tests:

1. Maximal oxygen uptake (VO₂max)
2. Submaximal running tests
3. 20 meter shuttle run performance

Muscle-level assessments:

1. Biopsies of the vastus lateralis muscle (outer thigh)
2. Analysis of mitochondrial markers
3. Gene and protein expression linked to endurance adaptation

This dual approach allowed the researchers to determine whether performance outcomes matched what was happening inside muscle cells. Sometimes they do. Sometimes they don't.

Results: When Performance and Biology Tell Different Stories

One of the most striking aspects of this study is the clear divergence between performance outcomes and molecular adaptations. What you see on a stopwatch doesn't always reflect what's happening in your mitochondria.

Performance Outcomes: No Obvious Harm

From a practical standpoint, endurance athletes care first about measurable performance. Can you run faster? Can you sustain higher power output? Can you go longer before fatigue sets in?

Maximal Oxygen Uptake (VO₂max)

Both groups improved their maximal oxygen uptake over the 11-week training period:

• Vitamin C and E group: approximately 8 ± 5 percent increase
• Placebo group: approximately 8 ± 5 percent increase

There was no significant difference between groups. High-dose antioxidant supplementation did not blunt improvements in VO₂max during the study period. On this metric, the supplements appeared neutral.

20 Meter Shuttle Run Performance

Performance on the shuttle run test also improved in both groups:

• Vitamin C and E group: approximately 10 ± 11 percent improvement
• Placebo group: approximately 14 ± 17 percent improvement

Despite numerically larger gains in the placebo group, the difference did not reach statistical significance. The study detected no significant performance interaction between supplementation and training.

From a surface-level view, these results might lead an athlete to conclude that antioxidant supplementation is harmless. Performance improved. Training worked. What's the problem?

Cellular Adaptations: A Different Picture Emerges

The story changed dramatically when researchers examined what was happening inside muscle tissue.

Mitochondrial Marker COX4

Cytochrome c oxidase subunit IV (COX4) is commonly used as a marker of mitochondrial content in skeletal muscle. More mitochondria means greater aerobic capacity at the cellular level.

• Placebo group: +59 ± 97 percent increase
• Vitamin C and E group: -13 ± 54 percent change

The difference between groups was statistically significant, strongly favoring placebo. This indicates that mitochondrial-related adaptations were markedly blunted in the antioxidant group. While the placebo group showed substantial increases in this marker, the supplemented group showed essentially no change or even a slight decrease.

PGC-1α Expression: The Master Regulator

PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) is a central regulator of mitochondrial biogenesis and endurance adaptation. It's often called the master switch for aerobic metabolism.

• Placebo group: +19 ± 51 percent increase
• Vitamin C and E group: -13 ± 29 percent change

Again, the difference was statistically significant. The training-induced increase in this key regulator was attenuated with antioxidant supplementation. Instead of upregulating the master switch for mitochondrial development, the antioxidant group showed a downward trend.

Signaling-Related Gene Expression

The researchers also measured mRNA levels of genes involved in cellular signaling:

• CDC42 (cell division control protein 42)
• MAPK1 (mitogen-activated protein kinase 1)

Both were significantly lower in the vitamin C and E group compared with placebo. These genes are involved in cellular signaling cascades that respond to exercise stress and coordinate adaptive responses.

Key Finding: Markers of mitochondrial biogenesis and endurance-related cellular signaling were consistently blunted by high-dose vitamin C and E supplementation, even though overall performance improved similarly in both groups.

What This Study Actually Proves

Within the scope of this experiment, one conclusion is well supported by the data.

High-dose daily supplementation with vitamin C and vitamin E attenuates skeletal muscle signaling and mitochondrial biogenesis markers that are normally upregulated by endurance training. This effect was observed consistently across multiple molecular indicators and occurred during a realistic, structured training program in humans, not just in isolated cells or animal models.

The Mechanistic Implication: Stress as Signal

The findings support a concept that contradicts intuitive thinking about oxidative stress.

Reactive oxygen species (ROS) generated during exercise are not merely harmful byproducts that need to be neutralized. They also appear to play a role in signaling for endurance adaptation. When you exercise hard, your muscles produce ROS. Those ROS molecules interact with cellular proteins and transcription factors, triggering cascades that ultimately lead to gene expression changes, mitochondrial biogenesis, and improved aerobic capacity.

By aggressively reducing oxidative stress with high-dose antioxidants, some of these signals appear to be dampened. This doesn't eliminate adaptation entirely, but it alters the molecular environment in which adaptation occurs. You're still training, but you're training with the molecular volume turned down.

The Hormesis Principle

This concept aligns with the principle of hormesis: the idea that mild stressors can trigger beneficial adaptive responses. Not all stress is bad. In fact, controlled stress is the entire basis of training adaptation. Lift weights, damage muscle fibers, trigger repair that makes them stronger. Run intervals, stress cardiovascular system, trigger adaptations that improve oxygen delivery.

Oxidative stress during exercise appears to fit this pattern. It's part of the signal, not just noise to be eliminated.

What This Study Does NOT Claim

It's equally important to state clearly what the study does not demonstrate.

No Proven Performance Impairment

The study does not demonstrate reduced performance gains. Improvements in VO₂max and shuttle run performance were statistically similar between groups. An athlete looking only at race results over 11 weeks might see no difference.

No Long-Term Data

The study does not measure endurance race performance or outcomes beyond the laboratory and field tests used. It doesn't track what happens over years of supplementation or multiple training cycles.

No Health Risk Established

The study does not establish long-term health consequences of antioxidant supplementation. The focus was purely on training adaptations, not overall health, disease risk, or immune function.

Limited Generalizability

The study does not provide evidence for effects in other populations, such as elite athletes, older adults, or individuals with clinical conditions. The participants were healthy young adults.

Any claims beyond these boundaries would extend beyond what the data actually support.

Practical Applications for Endurance Athletes

For endurance athletes, coaches, and sports nutritionists, these results raise a strategic question rather than issuing a blanket prohibition.

Short-Term Performance vs. Long-Term Adaptation

In the short term, high-dose vitamin C and E did not prevent gains in VO₂max or shuttle run performance. An athlete preparing for a competition in 12 weeks might see little difference on race day.

However, endurance performance over months and years depends heavily on the accumulation of cellular adaptations: mitochondrial density, oxidative enzyme activity, capillary development, and efficient muscle metabolism. These traits are built through repeated cellular responses to training stress.

If you consistently dampen those responses with chronic high-dose antioxidant supplementation, the long-term trajectory of adaptation may be compromised even if short-term performance metrics look acceptable.

Reconsidering Supplementation Strategy

If the goal is to maximize the cellular foundation of endurance capacity, the data suggest that chronic use of high-dose antioxidant supplements during training periods may compromise key adaptive signals.

This doesn't mean antioxidants are harmful in all contexts. There may be situations where they're appropriate:

• Recovery periods: During tapering or rest weeks when adaptation isn't the priority
• Illness prevention: When immune function is the primary concern
• Extreme oxidative stress: In situations involving environmental stressors beyond normal training

But using large doses daily throughout a training block may not be neutral, even if immediate performance gains still occur.

Food-Based Antioxidants: A Different Story

It's worth noting that this study examined high-dose isolated supplements, not dietary antioxidants from whole foods. The doses used were far higher than what you'd get from eating fruits, vegetables, nuts, and other antioxidant-rich foods.

Whole food sources provide antioxidants in a complex matrix with fiber, polyphenols, and other compounds. The biological effects of eating blueberries or spinach are likely different from taking megadoses of isolated vitamins. This study doesn't argue against eating a nutrient-rich diet.

Study Limitations Worth Noting

Molecular Changes Don't Guarantee Performance Changes

Changes in molecular markers do not automatically translate to measurable performance differences within an 11-week timeframe. The relationship between signaling, adaptation, and performance unfolds over longer periods and involves many factors not captured by a single study.

Specific to These Doses

The results apply specifically to 1000 mg of vitamin C and 235 mg of vitamin E per day. The study does not address lower doses, different timing strategies, or dietary antioxidant intake from whole foods. The dose-response relationship remains unclear.

Mixed-Sex Sample Without Subgroup Analysis

Men and women were included, but subgroup analyses were not reported. Potential sex-specific responses related to hormonal differences or body composition cannot be evaluated from the available data.

Young, Healthy Population

The participants were young adults without chronic disease. Older individuals, elite athletes with different training histories, or people with health conditions might respond differently.

The Bigger Picture: Rethinking Recovery Supplements

This study is part of a larger body of research questioning whether the supplement industry's emphasis on blocking all forms of physiological stress is actually counterproductive.

The same pattern has emerged with other interventions:

• Anti-inflammatory drugs: May blunt hypertrophy when taken chronically around training
• Ice baths: May reduce adaptation signals when used immediately after resistance training
• Antioxidant supplements: May interfere with endurance adaptation signals, as shown here

The theme is consistent: controlled physiological stress drives adaptation. Interventions that eliminate that stress too aggressively may undermine the training process itself.

Summary: More Isn't Always Better

This controlled human trial provides a nuanced view of antioxidant supplementation in endurance training that challenges popular assumptions.

Key finding: High daily doses of vitamin C and vitamin E dampened cellular markers of endurance adaptation, including mitochondrial biogenesis signals and key gene expression, during an 11-week training program.

Complicating factor: Performance improvements in VO₂max and shuttle run tests were not significantly different between supplemented and placebo groups over this timeframe.

Practical implication: Antioxidants are not universally beneficial for athletes. When taken in high doses during endurance training, they may interfere with molecular signaling pathways that support long-term adaptation, even if short-term performance gains appear unaffected.

For endurance athletes, the decision to supplement should consider not only subjective recovery feelings and immediate performance, but also the potential trade-offs between reducing oxidative stress and preserving the signals that drive physiological improvement over time.

Sometimes the best recovery strategy isn't adding more supplements. It's allowing your body's natural adaptive responses to unfold without pharmaceutical interference.

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References and Further Reading

• Paulsen G, Hamarsland H, Cumming KT, et al. Vitamin C and E supplementation alters protein signalling after a strength training session, but not muscle growth during 10 weeks of training. Journal of Physiology. 2014;592(24):5391-5408. PMID: 25384777
• Ristow M, Zarse K, Oberbach A, et al. Antioxidants prevent health-promoting effects of physical exercise in humans. Proceedings of the National Academy of Sciences. 2009;106(21):8665-8670. PMID: 19433800
• Gomez-Cabrera MC, Domenech E, Romagnoli M, et al. Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performance. American Journal of Clinical Nutrition. 2008;87(1):142-149. PMID: 18175748