As a 62 yo marathon runner on a low carb diet, I’m mildly annoyed by everybody telling me I absolutely need carbohydrate gels to run past 10k and that I might even suffer from hypoglycemia and crash if not. The current trend is everywhere and now people are pushing to consume more than 90g/h.
In my case I run the marathons fasted and don’t drink any calories. That did not prevent me to qualify for the next Boston Marathon. I never had any crashes and I make my own glucose during the race even though I’m taking 25mg/day Empagliflozin and 5mg/week Tirzepatide and 7.5mg/day of Plioglitazone.
All that to say that this monumental paper (53 pages) has got me interested.
BTW All the authors are top level.
The paper is here: Carbohydrate Ingestion on Exercise Metabolism and Physical Performance
Gemini 3 pro analysis with the latest @RapAdmin prompt.
Carbohydrate Ingestion on Exercise Metabolism and Physical Performance
Role: Longevity Research Analyst and Science Journalist
Date: February 1, 2026
Source Material: Endocrine Reviews (Advance Access, Jan 21, 2026)
Part 1: Narrative Summary
The Big Idea: For over 50 years, sports nutrition has been governed by the “Anaplerotic Theory”—the belief that muscle glycogen depletion is the catastrophic failure point of endurance, necessitating aggressive high-carbohydrate (CHO) intake. This landmark review by Timothy Noakes, Jeff Volek, Dominic D’Agostino, and colleagues dismantles this dogma. By re-analyzing over 100 years of data (including 160+ studies), the authors argue that fatigue is not a “muscle energy crisis” but a brain-derived safety mechanism triggered by Exercise-Induced Hypoglycemia (EIH). The brain protects its own fuel supply (the “Small Glucose Pool” in the blood and liver) by throttling muscle recruitment long before muscle glycogen (the “Large Glucose Pool”) runs dry. The practical implication is a paradigm shift: athletes do not need to “stuff” themselves with 90g/h of carbohydrates. Instead, minimal CHO intake (~15g/h) or fat-adaptation—which unlocks fat oxidation rates double that of current textbooks—is sufficient to prevent EIH and maximize performance, even at high intensities.
Context:
- Institution: University of Cape Town (SA), Ohio State University (USA), University of South Florida (USA), Florida Institute for Human and Machine Cognition (USA).
- Journal: Endocrine Reviews.
- Impact Evaluation: The impact score of this journal is 22.0 (JIF 2024), evaluated against a typical high-end range of 0–60+ for top general science, therefore this is an Elite impact journal.
Part 2: The Biohacker Analysis
Study Design Specifications:
- Type: Comprehensive Narrative Review and Re-analysis of Historical Data (Meta-synthesis).
- Subjects: Humans (primary focus on trained cyclists, runners, and ultra-endurance athletes).
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Lifespan Analysis: N/A. This study focuses on human exercise metabolism and performance, not lifespan determination.
- Constraint Check: As this paper presents no new murine lifespan data, a comparison against the “900-day rule” for control mice (per Biorxiv 2023.10.08.561459v1) is not applicable.
- Lifespan Data: None.
Mechanistic Deep Dive:
- The Central Governor & Neuroglycopenia: The authors propose that the brain monitors the Small Glucose Pool (SGP)—blood glucose and liver glycogen. When the SGP is threatened (EIH), the brain induces central fatigue to prevent neuroglycopenic coma. This overrides peripheral muscle status.
- Metabolic Flexibility & Mitochondrial Dynamics: The review highlights that fat-adapted athletes can achieve Peak Fat Oxidation (PFO) rates of >1.5 g/min (previously capped at 1.0 g/min in textbooks) and sustain this up to 85% VO2max. This suggests that mitochondrial beta-oxidation capacity is vastly underutilized in high-carb athletes due to insulin-mediated suppression.
- Longevity Relevance: By minimizing hyperglycemic excursions and insulin load during exercise, this model aligns with AMPK activation and mTOR suppression (fasted/low-carb state), potentially enhancing autophagy compared to the “glucose-fed” model.
Novelty:
- Historical Correction: It recovers lost data from the 1930s (Boje, Christensen) showing that reversing hypoglycemia restores performance without replenishing muscle glycogen.
- Dose-Response Myth: It debunks the “more is better” CHO guideline, showing that ~10–15g/h is often statistically equivalent to 90g/h for performance, provided EIH is prevented.
Critical Limitations:
- Review Bias: The authors (Noakes, Volek, D’Agostino) are known proponents of Low-Carb/Keto paradigms; while the data re-analysis is rigorous, the interpretation strongly favors their established “Central Governor” and “Fat Adaptation” theories.
- Translational Gap (Elite vs. Average): Data often relies on elite or highly trained ultra-endurance athletes (e.g., FASTER study cohorts). The metabolic flexibility of a metabolically unhealthy amateur may not mirror these findings.
- Missing Data: Long-term safety data on maintaining “chronic” ketosis in high-volume athletes (regarding kidney load or cortisol levels) is not the focus of this review.
Part 3: Claims & Evidence Hierarchy
Claim 1: Exercise fatigue is primarily central (brain-regulated) to prevent hypoglycemia, not due to muscle glycogen depletion.
- Support: Re-analysis of Coyle (1983, 1986) and classic Scandinavian studies shows fatigue correlates with blood glucose drops, not muscle glycogen levels.
- Verification: Confirmed by “Central Governor Model” literature.
- Hierarchy: Level B (Re-analysis of RCTs).
- Translational Uncertainty: Low. Human data.
Claim 2: Fat-adapted athletes can oxidize fat at rates >1.5 g/min, sustaining exercise at intensities >85% VO2max.
- Support: Cites Prins et al. (2023) and Volek et al. (FASTER study) showing PFO of ~1.54 g/min vs 0.67 g/min in high-carb controls.
- Verification: Verified. The FASTER study (Volek 2016) and Prins (2023) confirm these rates High fat diet improves metabolic flexibility (2023).
- Hierarchy: Level C (Observational/Cross-sectional studies of elite phenotypes).
- Translational Uncertainty: High. Applies specifically to keto-adapted phenotypes, not general population.
Claim 3: There is no dose-response benefit to CHO ingestion >15–30 g/h; preventing hypoglycemia is the only requirement.
- Support: Multiple studies (Smith 2010, 2013) show no performance difference between moderate and high CHO doses.
- Verification: Controversial. Current guidelines (ACSM) recommend up to 90g/h for ultra-endurance.
- Hierarchy: Level A (Systematic Review of multiple trials).
Claim 4: High carbohydrate intake suppresses fat oxidation and may accelerate glycogen usage.
- Support: Insulin response to CHO locks out lipolysis, forcing reliance on the limited LGP.
- Verification: Verified. Basic physiological fact (Randle Cycle).
- Hierarchy: Level A (Established Mechanism).
Part 4: Actionable Intelligence
The Translational Protocol (Metabolic Preservation):
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Protocol: “The SGP Defense Strategy”
- Goal: Prevent EIH (Blood Glucose drop) without shutting down fat oxidation.
- Dosage: 10–20g CHO per hour (approx. 40–80 kcal/h) during exercise >2 hours. This is drastically lower than the standard 60–90g/h advice.
- Form: Slow-release starch or glucose polymers to maintain euglycemia without spiking insulin.
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Pharmacokinetics (PK/PD):
- Bioavailability: Glucose/Maltodextrin is rapidly absorbed. However, high doses (>60g/h) often exceed intestinal transporter capacity (SGLT1), causing GI distress. The low-dose protocol mitigates this risk.
- Half-life: Exogenous glucose is oxidized within minutes during exercise.
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Safety & Toxicity:
- Hypoglycemia: The primary risk is under-fueling in non-fat-adapted individuals. If you are not keto-adapted, 10g/h might be insufficient to prevent bonking if glycogen stores are low.
- Toxicity: High CHO intake (>90g/h) is linked to significant GI distress (nausea, bloating, diarrhea) in up to 30-50% of ultra-athletes.
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Biomarker Verification Panel:
- Efficacy: Continuous Glucose Monitor (CGM). Aim for “flatline” stability. Drops >10-15 mg/dL from baseline often precede fatigue.
- Metabolic Flex: RQ (Respiratory Quotient) testing. Target RQ ~0.70–0.75 at Zone 2/3 intensities (indicating high fat ox).
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Feasibility & ROI:
- Cost: Negligible. Reducing gels/powders from 90g/h to 15g/h saves money and gut health.
- Benefit: Elimination of GI issues, stable energy, improved metabolic flexibility.
Part 5: The Strategic FAQ
1. “Does this low-carb approach conflict with my Rapamycin protocol?”
- Answer: Likely complementary. Rapamycin inhibits mTORC1, mimicking a fasted state. High-carb fueling activates mTOR/insulin, potentially negating Rapamycin’s longevity signaling. A low-carb/fat-adapted exercise state aligns synergistically with Rapamycin’s inhibition of the nutrient-sensing pathway. [Confidence: Medium - Mechanistic Alignment]
2. “I take Metformin for longevity. Will this blunt my adaptation to the low-carb training?”
- Answer: Potential interaction. Metformin activates AMPK but can blunt mitochondrial adaptations to exercise (VO2max improvements) and may interfere with peak lactate clearance. In a low-carb context, Metformin might exacerbate the perception of effort by limiting hepatic gluconeogenesis, threatening the SGP (Small Glucose Pool). [Confidence: High - Clinical Data exists on Metformin blunting exercise adaptation]
3. “Can I use Exogenous Ketones (BHB Esters) instead of the 15g CHO?”
- Answer: Yes, theoretically. The authors (D’Agostino/Volek) are pioneers in this. Ketones provide an alternative brain fuel, potentially bypassing the “Central Governor’s” glucose dependency. However, safety data on long-term ester use is less robust than glucose. [Confidence: High]
4. “What about the ‘Train Low, Race High’ protocol? Does this paper support it?”
- Answer: No. The paper suggests “Race Low” (or “Race Moderate”) is sufficient. It argues that reintroducing high carbs blocks the fat oxidation advantage you built during training.
5. “Is this protocol safe for females?”
- Answer: Data Absent. Most cited studies (e.g., FASTER) are male-dominant. Females may have different sensitivity to low energy availability (RED-S) and EIH. Proceed with caution.
6. “If I am not keto-adapted, will 15g/h cause me to bonk?”
- Answer: Yes. The protocol assumes a degree of metabolic flexibility. A “sugar-burner” relying solely on 15g/h without prior fat adaptation will likely deplete glycogen and trigger EIH. Adaptation takes weeks.
7. “Does this apply to HIIT or CrossFit?”
- Answer: The paper focuses on prolonged exercise (>2-3 hours). For short, supramaximal efforts (glycolytic), the LGP (muscle glycogen) is still the dominant limiter. Do not apply this to a 20-minute sprint workout.
8. “How does this impact Acarbose users?”
- Answer: Acarbose blocks starch breakdown. Using it during exercise with this protocol would be counterproductive, as you need that small 15g stream to hit the blood to placate the brain.
9. “What is the specific danger signal on my CGM I should watch for?”
- Answer: A drop below your baseline (fasting) glucose, or a rapid rate of descent. The absolute number matters less than the relative drop.
10. “Does high-fat feeding impair cardiac efficiency?”
- Answer: Some older data suggested increased Free Fatty Acids (FFA) increase cardiac oxygen demand (oxygen wasting). However, the authors argue that in adapted athletes, efficiency is maintained. [Confidence: Low - Controversial Area]
Relevant Video:
Jeff Volek: The Many Facets of Keto-Adaptation
This video is relevant because Dr. Jeff Volek (a co-author of the analyzed paper) details the FASTER study data, specifically explaining how fat-adapted athletes achieve the high oxidation rates (>1.5g/min) central to the paper’s claims.