D-Ribose

NutraPedia - Evidence-Based Supplement Research

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Health Goals: energy muscle heart

Research Overview

Across the abstracts provided, D-ribose has been most studied in contexts where impaired cellular energy metabolism is hypothesized to contribute to symptoms or functional limitation—particularly cardiovascular disease (myocardial ischaemia, coronary artery disease with congestive heart failure, and HFpEF) and, to a lesser extent, fatigue-related syndromes (fibromyalgia/chronic fatigue syndrome) and exercise recovery/performance. The cardiovascular literature includes small controlled trials and a larger phase 2 randomized, double-blind, placebo-controlled trial in HFpEF evaluating patient-reported outcomes and cardiac/biochemical measures. In contrast, the fibromyalgia/CFS evidence here comes from an open-label, uncontrolled pilot study, and the exercise literature includes mixed findings from randomized trials in athletes and healthy participants using dextrose comparators.

The strongest evidence in this set supports potential benefit in cardiac populations, where randomized, blinded designs report improvements in some physiologic measures and/or symptoms. Specifically, short-term ribose supplementation improved treadmill time to ECG evidence of ischaemia (time to 1 mm ST-segment depression) in men with severe coronary artery disease, consistent with increased ischaemia tolerance. In chronic coronary disease with CHF, a small randomized crossover study found improvements in echocardiographic indices of diastolic function and quality of life versus placebo. In HFpEF, a phase 2 randomized, double-blind, placebo-controlled trial reported improvements in symptom scores (KCCQ), vigor, ejection fraction, and selected biomarkers, although functional capacity (6-minute walk) and a key diastolic parameter (E/e’) did not significantly improve. Outside cardiology, evidence is less definitive: the uncontrolled FMS/CFS pilot reported broad symptom improvements, but the design limits causal inference; and in sport/exercise settings, results are inconsistent, including a trial in collegiate rowers where dextrose outperformed ribose for time-trial improvement, alongside another study suggesting possible benefits in less aerobically fit individuals during repeated high-intensity training.

Key gaps include the need for larger, well-powered, independently replicated randomized controlled trials that isolate D-ribose effects (including dose–response and duration), confirm clinically meaningful endpoints (e.g., hospitalization, exercise capacity, validated symptom scales), and clarify which subgroups benefit (e.g., HFpEF phenotypes; trained vs untrained individuals). Mechanistic work linking supplementation to tissue-level ATP repletion in humans remains important, as do standardized comparisons against appropriate controls (placebo vs carbohydrate-matched comparators) to separate ribose-specific effects from general caloric/carbohydrate effects. Additional research should also more rigorously characterize safety and tolerability across populations and longer follow-up, given that much of the current evidence base is short-term and includes small samples or non-controlled designs.

1. What conditions has D-Ribose been studied for?

  • Fibromyalgia (FMS) and chronic fatigue syndrome (CFS): Studied in an open-label pilot trial using 5 g three times daily.

  • Coronary artery disease (CAD) / myocardial ischemia (exercise-induced ischemia): Studied in men with severe CAD given oral ribose 60 g/day for 3 days, assessing treadmill ischemia thresholds (ST-segment depression) and angina timing.

  • Congestive heart failure (CHF) in patients with chronic coronary heart disease: Studied in a prospective, double-blind, randomized, crossover trial (3-week periods) assessing echocardiographic diastolic parameters and quality of life.

  • Heart failure with preserved ejection fraction (HFpEF): Studied in a phase 2 randomized, double-blind, placebo-controlled trial (12 weeks) testing d-ribose (15 g/day) and/or ubiquinol (600 mg/day) with symptoms and cardiac biomarkers/performance outcomes.

  • Athletic performance and exercise recovery (various protocols):

    • Rowing performance in collegiate women rowers (ribose vs dextrose for 8 weeks).

    • High-intensity interval cycling over multiple days in healthy subjects (10 g/day ribose vs 10 g/day dextrose; subgrouped by VO2max).

    • ATP resynthesis after 1 week of intense sprint training (ribose 200 mg/kg three times daily for 3 days vs placebo) with muscle ATP measured.

    • Short-term anaerobic cycle sprint performance after 32 g ribose over 36 hours vs cellulose placebo.

    • Repeated maximal knee-extension training with ribose 4 g four times daily vs placebo; included muscle biopsy subgroup for ATP recovery.

    • Trained males performing repeated Wingate tests (abstract truncated, but clearly an ergogenic-performance context).

2. Does it work in treating those conditions? Summarize the evidence.

  • FMS/CFS: One open-label, uncontrolled pilot study (41 patients) reported statistically significant improvements in energy, sleep, mental clarity, pain intensity, and well-being, with ~66% reporting “significant improvement” and large VAS changes (e.g., energy +45%, well-being +30%; p<0.0001). Major limitation: no placebo control and subjective endpoints, so placebo effects/regression to the mean cannot be excluded.

  • CAD / ischemia tolerance: In a randomized placebo-controlled study in 20 men with severe CAD, 3 days of ribose (60 g/day in four doses) increased treadmill time to 1 mm ST-segment depression versus placebo (276 vs 223 seconds; p=0.002). Time to moderate angina did not differ between groups, though within the ribose group both time-to-ST-depression and time-to-angina improved from baseline (p<0.005). This suggests improved ischemia tolerance, but the study is small and short-term.

  • CHF (with CAD): In a double-blind randomized crossover feasibility study (15 patients; 3-week periods), ribose improved several echocardiographic diastolic parameters (e.g., atrial contribution to LV filling 40% to 45%, P=0.02; smaller left atrial dimension, P=0.02; shorter E-wave deceleration time, P=0.002) and improved SF-36 quality of life (P≤0.01). Small sample size and feasibility design limit certainty, but the blinded crossover design strengthens inference.

  • HFpEF: A phase 2 randomized, double-blind, placebo-controlled trial (216 patients; 12 weeks; four arms) reported that treatment with ubiquinol and/or d-ribose significantly improved symptom score (KCCQ clinical summary), vigor, and EF, and reduced BNP and lactate/ATP ratio. However, key limitation for attributing effects specifically to d-ribose: the abstract reports improvements for “ubiquinol and/or d-ribose” across groups rather than clearly isolating the d-ribose-only effect versus placebo for each endpoint. Also, no significant improvement was seen in septal E/e’ or 6-minute walk distance.

  • Athletic performance/recovery: Results are mixed and often negative for performance outcomes.

    • Rowing: In a double-blind randomized trial (31 women rowers), the dextrose group improved more than the ribose group in 2000-m time trial performance at 8 weeks (median improvement 15.2 vs 5.2 seconds; P=0.031). Authors hypothesized dextrose enhanced performance; ribose did not show benefit here.

    • Multi-day high-intensity interval exercise: In 26 healthy subjects (double-blind crossover; 10 g/day ribose vs 10 g/day dextrose), the lower-VO2max subgroup showed better maintenance/improvement in mean and peak power output from day 1 to day 3 with ribose, and lower perceived exertion and creatine kinase versus dextrose; no differences in the higher-VO2max subgroup. This suggests possible benefit in less-trained individuals under repeated stress, but it is subgroup-dependent.

    • Muscle ATP resynthesis after intense training: In 8 subjects after 1 week of sprint training, ribose (200 mg/kg three times daily for 3 days) restored muscle ATP to near pretraining levels by 72 hours, while placebo remained lower; however, mean and peak power output were similar between groups. This supports an effect on ATP resynthesis but not necessarily on performance.

    • Short-term anaerobic sprinting: A placebo-controlled crossover study found statistically significant increases in mean and peak power in sprint 2 after ribose, but effects were not consistent across all sprints; authors concluded no consistent/substantial effect.

    • Knee-extension training + ATP recovery: A double-blind randomized study (ribose 4 g four times daily) found no benefit on power output, lactate/ammonia responses, or muscle ATP recovery versus placebo, including in a biopsy subgroup.

3. What health benefits does it have?

  • Potential symptom relief in FMS/CFS: The uncontrolled pilot study reported improvements in energy, sleep, mental clarity, pain, and well-being after 5 g three times daily.

  • Cardiac ischemia tolerance in CAD: Short-term ribose (60 g/day for 3 days) increased treadmill time to objective ischemic ECG changes (1 mm ST depression) compared with placebo.

  • Diastolic function and quality of life in CHF (with CAD): In a small blinded crossover study, ribose improved echocardiographic diastolic filling parameters and SF-36 quality of life.

  • HFpEF symptom and biomarker improvements (possibly, and not clearly attributable to ribose alone): In a 216-patient phase 2 trial, supplementation with ubiquinol and/or d-ribose improved KCCQ symptom score, vigor, EF, BNP, and lactate/ATP ratio, but did not improve E/e’ or 6-minute walk distance.

  • ATP resynthesis after intense exercise: Some evidence shows faster restoration of muscle ATP after heavy training (ATP normalized by 72 hours with ribose vs still depressed with placebo), though performance benefits were not consistently demonstrated.

4. Does it have any downsides or side effects?

  • Tolerability (limited reporting in these abstracts): The FMS/CFS pilot study explicitly states ribose was “well-tolerated.” The other abstracts provided do not describe adverse events in detail, so safety conclusions are limited.

  • Possible lack of benefit or opportunity cost: Multiple athletic studies found no consistent performance benefit, and one trial in rowers showed less improvement with ribose than with dextrose. This is not a “side effect” per se, but it is a practical downside if used for performance enhancement.

  • Unknowns from these abstracts: These summaries do not provide systematic data on gastrointestinal effects, hypoglycemia, or other metabolic effects sometimes discussed with ribose elsewhere; based on the provided abstracts alone, adverse-effect profiling is incomplete.

5. Is it beneficial or harmful for any genetic variations (pharmacogenomics)?

The provided abstracts do not evaluate genetic variants or report pharmacogenomic subgroup analyses (e.g., responders by genotype). Therefore, based on these abstracts, there is no direct evidence that D-ribose is beneficial or harmful specifically in relation to particular genetic variations.

References

  1. The use of D-ribose in chronic fatigue syndrome and fibromyalgia: a pilot study
    Jacob E Teitelbaum, Clarence Johnson, John St Cyr (2006)
  2. D-Ribose improves diastolic function and quality of life in congestive heart failure patients: a prospective feasibility study
    Heyder Omran, Stefan Illien, Dean MacCarter, John St Cyr, Berndt Lüderitz (2003)
  3. Effects of ribose on exercise-induced ischaemia in stable coronary artery disease
    W Pliml, T von Arnim, A Stäblein, H Hofmann, H G Zimmer (1992)
  4. Effects of Ubiquinol and/or D-ribose in Patients With Heart Failure With Preserved Ejection Fraction
    Janet D Pierce, Qiuhua Shen, Diane E Mahoney, Faith Rahman, Kathryn J Krueger (2022)
  5. Ribose versus dextrose supplementation, association with rowing performance: a double-blind study
    Laura Dunne, Sarah Worley, Michael Macknin (2006)
  6. The influence of D-ribose ingestion and fitness level on performance and recovery
    John G Seifert, Allison Brumet, John A St Cyr (2017)
  7. Effect of ribose supplementation on resynthesis of adenine nucleotides after intense intermittent training in humans
    Y Hellsten, L Skadhauge, J Bangsbo (2004)
  8. Effects of ribose supplementation on repeated sprint performance in men
    John M Berardi, Tim N Ziegenfuss (2003)
  9. No effects of oral ribose supplementation on repeated maximal exercise and de novo ATP resynthesis
    B O Eijnde, M Van Leemputte, F Brouns, G J Van Der Vusse, V Labarque (2001)
  10. Effects of oral D-ribose supplementation on anaerobic capacity and selected metabolic markers in healthy males
    R B Kreider, C Melton, M Greenwood, C Rasmussen, J Lundberg (2003)
  11. Effects of ribose supplementation prior to and during intense exercise on anaerobic capacity and metabolic markers
    C Kerksick, C Rasmussen, R Bowden, B Leutholtz, T Harvey (2005)
  12. The role of ribose on oxidative stress during hypoxic exercise: a pilot study
    John G Seifert, Andrew W Subudhi, Min-Xin Fu, Karen L Riska, Jeff C John (2009)
  13. Effect of D-ribose supplementation on delayed onset muscle soreness induced by plyometric exercise in college students
    Wei Cao, Junqiang Qiu, Tianwei Cai, Longyan Yi, Dan Benardot (2020)


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