D-Ribose for energy production

With one in eight people feeling tired all the time, managing energy levels has become an important area of concern when looking at how we can optimise our health.

This week’s blog looks in detail at D-ribose, a crucial molecule in helping our body produce energy and whether supplementing with D-ribose can improve this process.

Energy production: An overview ^1,2

To generate energy the body relies on an adequate supply of adenosine triphosphate (ATP), which is the essential energy source for all living cells produced through cellular respiration. ATP needs to be constantly produced and replenished to sustain energy, for all bodily processes and any form of activity or exercise.

The two main fuel supplies for the body are fats and carbohydrates, the latter being the most efficient as it can be rapidly broken down into glucose for immediate energy.

Glucose from food is broken down via glycolysis, leading to the production of pyruvate which is then oxidized in the mitochondria before undergoing steps to become acetyl-CoA, this then fuels the next stage of cellular respiration, the Krebs cycle.

Fats can also be used for energy by the liberation of triglycerides allowing for the production of free fatty acids, which are used to create acetyl-CoA in a process called beta-oxidation.

Ketone bodies are compounds produced by the liver for energy when glucose is not available, using fats for fuel is referred to as ketosis and more information can be found at Benefits and cautions of a ketogenic diet – Cytoplan.

Acetyl-CoA enters the Krebs cycle which takes place inside the mitochondria. This is also where both nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FADH) are made, performing their functions as electron carriers that transport energy through the electron transport chain (ETC) and oxidative phosphorylation to activate ATP.

The mitochondria, the powerhouse of cell, can convert glucose into ATP via both aerobic (with oxygen) and anaerobic (without oxygen) respiration. In aerobic exercise the mitochondria have enough oxygen to be able to make ATP to perform an activity, however during anaerobic exercise (when you are out of breath) the body relies on anaerobic glycolysis to produce energy.

This occurs when there is not enough oxygen available, causing the mitochondrial process to become backed up and energy not being produced quick enough to meet demand. Pyruvate is unable to enter the Kreb’s cycle but can instead be converted to lactic acid, which can then be fermented, to produce ATP anaerobically.

Diagram ¹

D-Ribose and energy production ³

Skip to Key Takeaways

The mitochondria are the site of 99% of the body’s energy production, with ATP being present in the cytoplasm and nucleoplasm of every cell, making it the main energy source for intracellular metabolic pathways.

Healthy cells are readily able to replace their ATP stores to provide the body with cellular energy, however, when the body is under stress, vital tissues such as the skeletal and heart muscles may not be able to replenish levels of ATP quick enough for optimal functioning.

Any dysfunction of the mitochondria reduces the efficiency of cellular respiration and thus reduced energy production.

D-Ribose, a monosaccharide is a naturally occurring sugar molecule that is the main building block of ATP. The body’s cells can naturally produce D-ribose via the pentose phosphate pathway (PPP), a metabolic pathway parallel to glycolysis, however, this process is often slow due to the lack of enzymes needed to shunt glucose in the pathway of ribose synthesis.

Supplemental D-ribose however, bypasses this rate controlling PPP pathway, providing an alternative source of 5-phospho-D-ribose 1- pyrophosphate (PRPP) for ATP production, therefore providing a natural readily available ‘substrate’ for ATP synthesis. 

D-Ribose and athletic performance ⁴

Exercise supports both physical and psychological health, metabolically it increases glycogen synthesis, regulates insulin and promotes fat oxidation, as well as having a number of benefits to cardiovascular and overall health.

During exercise that reaches or exceeds anaerobic capacity, ATP is quickly depleted in the skeletal muscle resulting in an energy imbalance which can lead to fatigue and poor exercise performance. Replenishing ATP, through the use of D-Ribose, has been of interest to the fitness community and athletes for some time.

As discussed, D-Ribose is an essential component of the respiratory, skeletal and nervous system that may facilitate and assist in the resynthesis and recovery of ATP to fuel further training.

But what does the research on supplementing with D-ribose say?

One double blind crossover study looked into D-ribose supplementation on exercise performance and recovery by dividing participants into groups based on their peak V02 results.

The study, lasting 5 days, involved a loading period of 2 days followed by 10g a day of either D-ribose or dextrose as the control. They found that those who supplemented with D-ribose performed better on peak output tests between days 1 and 3, and reported reduced rates of perceived exertion compared to the control group. ⁴

Supplementation also shows promise in improving recovery after exercise by reducing muscle damage and soreness, often referred to as delayed onset muscle soreness (DOMS), which is found to peak between 24 to 72 hours after exercise.

DOMS is thought to occur due to a range of factors such as increased inflammation and oxidative stress, and the increase in pain causing substances including leukotrienes, bradykinin and prostaglandin. Enhancing the recovery rate of ATP may therefore help to shorten DOMS, with research finding that D-ribose taken at intervals throughout exercise did help to reduce muscle soreness and muscle damage post workout, quickened recovery time and inhibited the formation of lipid peroxides. ⁵

D-ribose for exercise performance may therefore enhance workout stamina and endurance by boosting muscle energy during physical activity, supporting blood flow and supporting and shortening recovery time between workouts.

D-Ribose and chronic fatigue ^5-9

Chronic fatigue syndrome (CFS) and myalgic encephalomyelitis (ME) are multifactorial conditions that are thought to involve dysfunctions in multiple body systems, including the neurologic, immunologic, endocrinologic, cardiovascular, and metabolic systems.

Intense physical and mental exhaustion, that is not improved by rest, is a common feature of CFS and ME, leading to researchers looking into options to support normal energy production, ATP recycling and exercise tolerance.

Characteristics of CFS include post exertional fatigue, poor exercise tolerance and reduced stamina; which is thought to be a result of insufficient ATP production and mitochondrial dysfunction.

Research suggests that those with CFS have up to 80% lower levels of ATP than healthy subjects which significantly effects energy output, alongside the subsequent physical and psychological challenges.

Reduced energy production can also affect hypothalamic functioning, which can then have a knock-on effect on hormonal levels and sleep, further exacerbating the condition.

The functioning of the mitochondria is paramount to overall health. While free radical production is a normal by-product of healthy mitochondrial functioning, dysfunctional mitochondria exceed normal free radical output and produce higher levels of oxidative damage, alongside reduce energy production.

Any damaged mitochondria must be cleared from the body via mitophagy to prevent excess reactive oxygen species (ROS), this then allows for the production of new healthy mitochondria via mitochondrial biogenesis.

The ability for D-Ribose to increase cellular and muscular energy production makes it a promising supplement for those with CFS, ME and fibromyalgia, conditions associated with impaired cellular energy metabolism and mitochondrial dysfunction.

Disruptions in energy metabolism manifest as extreme fatigue, chronic muscle shortening, poor exercise tolerance and slow recovery from activity and so supplementing with D-ribose allows for the bypassing of the rate limiting enzymes of the PPP pathway and provides a readily available ATP substrate for enhancing energy output.

Researchers undertaking an initial pilot study found that D-Ribose significantly reduced symptoms of chronic fatigue and fibromyalgia in all areas tested including mental clarity, well-being, pain, sleep and energy.

The authors then conducted a further trial with 257 patients diagnosed with CFS or ME, who all supplemented D-ribose for 3 weeks. Findings revealed that 61.3% of people had an increased in energy, 30% in mental clarity and 37% of overall enhanced well-being, suggesting that D-ribose may play a role as a therapeutic tool in the management of energy dysfunction.^6,8,9

D-Ribose therefore may be an applicable supplement, as part of a wider protocol, to support energy production at a cellular level.

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References

1. Kenney, W.L., Wilmore, J.H. and Costill, D.L. (2019). Physiology of Sport and Exercise. [online] Google Books. Human Kinetics. Available at: https://books.google.co.uk/books/about/Physiology_of_Sport_and_Exercise.html?id=KNuDDwAAQBAJ&redir_esc=y.

2. Naifeh, J. and Varacallo, M. (2018). Biochemistry, Aerobic Glycolysis. [online] Nih.gov. Available at: https://www.ncbi.nlm.nih.gov/books/NBK470170/.

3. Mahoney DE, Hiebert JB, Thimmesch A, et al. Understanding D-Ribose and Mitochondrial Function. Adv Biosci Clin Med. 2018;6(1):1-5. doi:10.7575/aiac.abcmed.v.6n.1p.1

4. Seifert JG, Brumet A, St Cyr JA. The influence of D-ribose ingestion and fitness level on performance and recovery. J Int Soc Sports Nutr. 2017;14:47. Published 2017 Dec 20. doi:10.1186/s12970-017-0205-8

5. Cao W, Qiu J, Cai T, Yi L, Benardot D, Zou M. Effect of D-ribose supplementation on delayed onset muscle soreness induced by plyometric exercise in college students. J Int Soc Sports Nutr. 2020;17(1):42. Published 2020 Aug 10. doi:10.1186/s12970-020-00371-8

6. Teitelbaum, J. (2012). Treatment of Chronic Fatigue Syndrome and Fibromyalgia with D-Ribose– An Open-label, Multicenter Study. The Open Pain Journal, 5(1), pp.32–37. doi:https://doi.org/10.2174/1876386301205010032.

7. Popov LD. Mitochondrial biogenesis: An update. J Cell Mol Med. 2020;24(9):4892-4899

8. Teitelbaum JE, Johnson C, St Cyr J. The use of D-ribose in chronic fatigue syndrome and fibromyalgia: a pilot study. J Altern Complement Med. 2006;12(9):857-862. doi:10.1089/acm.2006.12.857
9. Myhill S, Booth NE, McLaren-Howard J. Chronic fatigue syndrome and mitochondrial dysfunction. Int J Clin Exp Med. 2009;2(1):1-16.

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Last updated on 17th July 2024 by cytoffice