D-Ribose: A Simple Sugar With A Complex Story

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Key Information

Supplemental D-ribose has been shown to improve cellular processes when there is mitochondrial dysfunction.

D-ribose is a naturally occurring monosaccharide within the metabolic pathway that assists with ATP production

D-ribose is an energy producing substrate of the ATP molecule and is often called the “molecular currency”

Excess serum d-ribose is correlated to higher neurodegeneration

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Hey there! Welcome to my review of D-ribose!

I recently came across a long thread asking whether they should supplement with d-ribose.

On the one hand, this simple sugar found in every cell is critical to your health and wellbeing1Zeba Siddiqui et al, Prevalence of auto-antibodies against D-ribose-glycated-hemoglobin in diabetes mellitusGlycobiology. 2019.

On the other hand, some research points to poor health consequences when it is found in excess in the body.

Not one to shy away from a supplement controversy, I decided to dig further into this myself, and what I found was truly surprising.

The following article details everything you need to know about supplementing with D-ribose, including what it is, how it works in the body, the science, mind-body benefits, side effects, dosing recommendations, and where to buy.  

If you’re ready to learn more about D-ribose, let’s jump into the article!

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A Closer Look at D-Ribose: How Does It Work?

D-Ribose is an essential monosaccharide with a pivotal role in our metabolism and energy production2Jinni Hong et al, D-ribose induces nephropathy through RAGE-dependent NF-κB inflammationArch Pharm Res. 2018. How? It is integral to creating Adenosine Triphosphate (ATP) — our cells’ energy powerhouse.

In other words, D-Ribose acts as a molecular refueler, powering up ATP production and, in turn, life’s most basic functions3Jinni Hong et al, D-ribose induces nephropathy through RAGE-dependent NF-κB inflammationArch Pharm Res. 2018.

The Heart of the Matter: D-Ribose and Cardiac Health

D-Ribose and Cardiac Health

Several research endeavors suggest that D-Ribose could benefit heart health4Shuai Li et al, D-ribose: Potential clinical applications in congestive heart failure and diabetes, and its complications (Review)Exp Ther Med. 2021. It may help improve the energy metabolism in the heart, offering a quality of life boost for those with specific heart conditions5Shuai Li et al, D-ribose: Potential clinical applications in congestive heart failure and diabetes, and its complications (Review)Exp Ther Med. 2021.

But a word of caution here: Always seek professional healthcare advice before beginning any new supplementation, especially if you have an existing heart condition.

The Brain’s Perspective: D-Ribose and Neurological Health

D-Ribose and Neurological Health

D-Ribose’s effect on brain health needs to be more clearly defined. A smaller study of 41 patients with chronic fatigue syndrome and/or fibromyalgia shows a subjective improvement in well-being and mental clarity when supplementing with D-Ribose6Jacob E Teitelbaum et al, The use of D-ribose in chronic fatigue syndrome and fibromyalgia: a pilot studyJ Altern Complement Med. 2006.

This sugary molecule could improve cognitive performance and mood7Jacob E Teitelbaum et al, The use of D-ribose in chronic fatigue syndrome and fibromyalgia: a pilot studyJ Altern Complement Med. 2006.

D-Ribose also plays a role in the pentose phosphate pathway, producing NADPH8Guoyao Wu et al, Glutathione metabolism and its implications for healthJ Nutr. 2004, a coenzyme with a vital job: to help regenerate the antioxidant glutathione, our brain’s line of defense against oxidative stress.

Moreover, D-Ribose assists in nucleotide synthesis. These nucleotides are the building blocks for our DNA and RNA — essential for cell growth, repair, and communication9Diane E. Mahoney et al, Understanding D-Ribose and Mitochondrial FunctionAdv Biosci Clin Med. 2018.

There’s a potential here that D-Ribose might benefit individuals struggling with various brain-related disorders, including Alzheimer’s disease, Parkinson’s disease, cognitive decline, and mental health issues like depression and anxiety.

D-Ribose and Alzheimer’s: A Possible Link?

Intriguingly, a cross-sectional study on 1725 patients aged 60 and older associated elevated urinary D-Ribose levels with increased cognitive decline rates10Xinyi Zhu et al, Urine D-ribose levels correlate with cognitive function in community-dwelling older adultsBMC Geriatrics. 2022. This could mean D-Ribose might be a practical, non-invasive biomarker for mental impairment progression.

However, no negative correlation between D-Ribose and cognitive function was seen in episodic memory, working memory, or processing speed tests.

Research suggests cognitive ability might be linked to D-Ribose metabolism11Jihui Lyu et al, A Brief Study of the Correlation of Urine D-ribose with MMSE Scores of Patients with Alzheimer’s Disease and Cognitively Normal Participants – American Journal of Urology ResearchResearch Gate. 2019. For example, D-Ribose plays a role in energy metabolism, a key process in Alzheimer’s Disease (AD). It’s also involved in ribosylation, linked to the production of advanced glycation end products (AGEs) — a risk factor for cognitive impairment12Yan Wei et al, Rapid glycation with D-ribose induces globular amyloid-like aggregations of BSA with high cytotoxicity to SH-SY5Y cellsBMC Cell Biology. 2009.

Here’s an essential caveat: The D-Ribose evaluated in these studies wasn’t a dietary supplement but a product of our cells’ energy metabolism.

A systematic review of animal studies reveals that D-ribose treatment might induce cognitive impairment, with more significant effects at higher doses13Ying Song et al, A systematic review and meta-analysis of cognitive and behavioral tests in rodents treated with different doses of D-riboseFront. Aging Neurosci. 2022

In rodents, D-ribose affected spatial learning tasks but not spatial memory tasks. Moreover, high D-ribose doses increased AGEs in the brain and serum, potentially causing cognitive impairment.

D-Ribose-mediated cognitive impairment’s complex mechanisms demand more research, including potential gender-based differences.

Balancing Blood Sugar: A Role for D-Ribose?

Balancing Blood Sugar: A Role for D-Ribose

D-Ribose’s impact on blood sugar levels is a puzzle.

D-Ribose is a monosaccharide like glucose, but its effect on blood glucose might be more adverse than we thought. Various studies across humans, animals, and cell cultures show D-Ribose’s capacity to generate glycosylated hemoglobin, an early diabetes detection marker14Xixi Chen et al, d-Ribose as a Contributor to Glycated HaemoglobinEBioMedicine. 2017.

Interestingly, D-Ribose outperforms other sugars in producing glycated serum protein (GSP), a precursor to chronic diabetes complications15Yao Chen et al, d-Ribose contributes to the glycation of serum proteinBiochim Biophys Acta Mol Basis Dis. 2019.

A notable observation here is that D-Ribose interacts more rapidly than glucose with non-enzymatic proteins in diabetic patients, leading to the formation of AGEs.

The binding of these AGEs to their receptors triggers a series of events: the upregulation of vascular growth factors, increased vascular permeability, angiogenesis, and local inflammation16Alejandra Planas et al, Advanced Glycations End Products in the Skin as Biomarkers of Cardiovascular Risk in Type 2 DiabetesInt J Mol Sci. 2022 . This AGE-receptor pathway activation also stimulates oxidative stress reactions, contributing to chronic diabetes complications.

Although D-Ribose might temporarily reduce blood sugar levels, its long-term accumulation can worsen diabetes complications. 17Mehjbeen Javed et al, D-ribose and pathogenesis of Alzheimer’s diseaseMol Biol Rep. 2020

Consequently, monitoring D-ribose levels and glycosylated proteins in diabetic patients might help forecast potential clinical complications, providing an opportunity for proactive prevention.

However, this hypothesis requires more research for confirmation.

D-Ribose as a Nootropic: A Good Fit?

Given the potential brain-health complications linked to high D-Ribose levels, classifying D-Ribose as a nootropic might be a stretch. However, numerous natural nootropics can prevent cognitive decline and boost brain health.

Beyond Heart and Brain: Other D-Ribose Benefits

D-Ribose’s contributions extend beyond brain and heart health:

Recommended Dose

The EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) states 36mg/kg bodyweight per day as an ideal recommended dose. 20EFSA Panel on Dietetic Products et al, Safety of d-ribose as a novel food pursuant to Regulation (EU) 2015/2283EFSA J. 2018

Wrapping Up

As you can see, the question as to whether you can benefit from D-ribose supplementation is tricky. While there are many positive aspects, many adverse outcomes correlate to high serum d-ribose. As more research comes to light, we can hopefully get a more straightforward answer, especially regarding brain health. Check with your doctor to determine whether D-ribose is right for you!

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Erik Abramowitz is a certified Nutritional Therapy Practitioner (NTP), Naturopathic Doctoral student, health coach, and father. He is the primary content creator for HolisticNootropics.com and the host of the Holistic Nootropics Podcast.

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