A growing body of evidence supports the use of supplements to enhance cycling performance through both direct and indirect mechanisms. This review was informed by a structured literature search conducted in PubMed, Scopus and Web of Science for peer-reviewed studies published up to May 2025. Studies were included if they involved human participants, were published in English and evaluated outcomes related to endurance performance, recovery or physiological function. Direct enhancement with ergogenic supplements is primarily achieved via modulation of skeletal muscle energy metabolism. During exercise, adenosine triphosphate (ATP) resynthesis is driven by the phosphagen system, glycolysis, oxidative phosphorylation and beta-oxidation, with each system contributing according to the intensity and duration of the effort. Supplements such as beta-alanine, caffeine, carbohydrates, carnitine, creatine monohydrate, dietary nitrates, electrolytes, exogenous ketones, N-acetylcysteine and sodium bicarbonate support these energy systems by improving substrate utilization, buffering capacity, energy availability or resistance to fatigue. In addition to ergogenic supplements that directly enhance performance, medical supplements play an important indirect role by supporting bone health, connective tissue integrity, inflammation management, micronutrient status, muscle repair and gut function. Evidence-based options for cyclists include calcium, cherry juice, collagen, curcumin, iron, multivitamins, omega-3 fatty acids, pickle juice, probiotics, protein, vitamin C, vitamin D and zinc. Each contribute to either improved recovery, immune support or long-term physiological adaptation. Evidence quality varied substantially across supplements, with strongest support for Australian Institute of Sport (AIS) Group A compounds. The integration of physiological testing including assessments of maximal oxygen consumption (VO2max), lactate threshold, metabolic substrate utilization and blood biomarkers may inform the development of individualized supplementation strategies tailored to training demands and competitive goals. This evidence-informed approach underscores the synergistic relationship between nutrition, training and performance optimization in cycling. Future research should explore personalized nutrition frameworks, interactions between multi-supplement protocols and the molecular mechanisms underpinning adaptation to endurance training and nutritional interventions.

Mitochondrial regulation in mesenchymal stem cells (MSCs) serves as a critical determinant of bone formation and skeletal homeostasis. While dietary nitrate and its transporter Sialin are implicated in systemic homeostasis, their specific roles in MSCs' function remain unclear. Here, we demonstrate that Sialin deficiency impairs MSCs' function and disrupts bone homeostasis. Gain- and loss-of-function studies reveal that Sialin localizes to the mitochondrial membrane and promotes osteogenic differentiation by maintaining mitochondrial bioenergetic integrity. Mechanistically, Sialin recruits pSTAT3S727 to mitochondria, forming a functional complex that activates mitochondrial bioenergy and stabilizes bone remodeling. Notably, dietary nitrate restores Sialin expression in aged mice, thereby enhancing MSCs' function and preventing osteoporosis. Our findings identify a nutrient-responsive signaling axis—nitrate-Sialin-pSTAT3S727—that promotes osteogenic differentiation via mitochondrial homeostasis, offering a potential therapeutic strategy for age-related osteoporosis.

Dietary Sources of Nitrate and Nitrite and Associations with Blood Pressure and Other Cardiovascular Disease Risk Factors in a Representative United Kingdom Population.

Endogenous formation of N-nitrosodimethylamine (NDMA) from dietary nitrite and nitrate intake and its association with cancer risk.

Increasing dietary nitrate (NO3-) through beetroot juice (BRJ) supplementation elicits acute ergogenic benefits. However, it is unknown whether chronic NO3- supplementation can enhance resistance training (RT) adaptations in middle-aged and older individuals. Therefore, we sought to determine whether 12 wk of combined RT and NO3- supplementation enhanced hypertrophic, vascular, strength, and skeletal muscle angiogenesis adaptations in this population. Twenty-eight apparently healthy, untrained men (M) and women (W) (56 ± 7 yr old and 29.1 ± 5.3 kg/m2 body mass index) completed 12 wk of supervised full-body RT (2×/wk) while ingesting either BRJ (140 mL daily, providing 800 mg NO3-; n = 14 with 7 M/7 W) or NO3--depleted BRJ placebo (PLA; n = 14 with 7 M/7 W). Participants underwent a whole body dual-energy X-ray absorptiometry scan, right mid-thigh ultrasonography for muscle imaging, right leg popliteal artery flow-mediated dilation (FMD) assessments, a biopsy of the right mid-thigh vastus lateralis, and strength testing before and following the 12-wk intervention. Biopsy analyses included a NO3-/nitrite (NOx) fluorometric assay, immunoblotting for proteins involved in angiogenesis, and immunohistochemistry to quantify fiber type-specific capillaries and cross-sectional areas. Muscle NOx values did not significantly change: +15.4% in BRJ (P = 0.073) and +7.8% (P = 0.514) in PLA. Both groups significantly improved measures related to muscle hypertrophy, strength, and FMD. However, no significant group × time interactions were observed for whole body lean mass, mid-thigh muscle cross-sectional area, popliteal artery FMD outcomes, or histological or molecular markers. In conclusion, these preliminary data on a limited number of participants indicate that BRJ supplementation does not enhance RT adaptations in middle-aged and older adults.NEW & NOTEWORTHY Results from this study suggest that 12 wk of dietary nitrate supplementation does not significantly alter skeletal muscle hypertrophic, strength, or vascular outcomes in previously untrained middle-aged and older adults who performed resistance training.

Background/Objectives: Vascular calcification is a major contributor to cardiovascular mortality and disability. Here, we investigated whether dietary nitrate, an exogenous source of nitric oxide (NO), could inhibit vascular calcification in a rat model induced by excess vitamin D3. Methods: The rats were injected subcutaneously with phosphate-buffered saline or 200,000 IU/kg cholecalciferol and the abdominal aorta was isolated 7 and 14 d after injection. Results: Von Kossa staining revealed mild vascular calcification 7 d after injection, with the positive area expanding by 14 d. Vasorelaxation induced by the NO donor sodium nitroprusside was normal 7 d after injection but weakened 14 d after injection. In a separate experiment, sodium nitrate (3 or 10 mM in drinking water) was administered for the last 7 and 13 d, prior to sacrifice, 14 d after cholecalciferol injection. Von Kossa staining-positive areas and calcium content in the abdominal aortas did not decrease with short-term administration of sodium nitrate but decreased with long-term administration; no difference in effect based on dosage was observed in either short-term or long-term administration. Low-dose sodium nitrate tended to increase plasma nitrite and nitrate levels, which are indicators of NO bioavailability, similar to both short- and long-term administration, which increased significantly at higher doses. Conclusions: These findings suggest that NO homeostasis in blood vessels deteriorates with the progression of vascular calcification, and that dietary nitrate may be a useful therapeutic approach.

Ingested nitrate and nitrite, drinking water disinfection by-products, and incidence of thyroid cancer among licensed pesticide applicators and spouses in the Agricultural Health Study.

Dietary nitrate (NO3 -) is an alternative non-protein nitrogen (NPN) source and has mitigation effects on enteric methane emission in ruminants. This study investigated the effects of NO3 - supplementation on rumen fermentation, nutrient digestibility, and nitrogen (N) utilization, focusing on urea-N and amino acid metabolism in sheep fed a high-forage diet. Six Suffolk wethers were assigned to a 2 × 2 crossover design conducted over two periods of 40 days each. Dietary treatments included supplementation with either urea (1.4% dry matter [DM]) or calcium nitrate tetrahydrate (5.8% DM). Each supplement contributed 32% of the daily crude protein supply (12% of DM). Intake, nutrient digestibility, N balance, ruminal volatile fatty acid (VFA) profiles, and plasma fluxes of urea-N and phenylalanine were not affected by NO3 - supplementation, with a trend (p = 0.075) toward reduced DM digestibility. Ruminal ammonia-N (p = 0.004) and plasma urea-N (p < 0.001) concentrations were lower, whereas ruminal NO3 --N (p = 0.045) and plasma glucose, triglycerides, and cholesterol concentrations were higher (p < 0.001) with NO3 - supplementation compared to urea. These results demonstrate that NO3 - can substitute for urea as an NPN source without affecting intake, ruminal VFA profiles, and urea-N production in sheep.

Dietary nitrate (NO3-) supplementation has been reported to improve cardiovascular health, but beyond its effects on brachial artery blood pressure (BP), dose-response effects on other cardiovascular variables are unclear. This study assessed the effects of three acute NO3- doses (200 mg, 400 mg, 800 mg NO3--rich beetroot powder) on brachial and aortic BP, arterial stiffness and macrovascular endothelial function, in a double-blind, randomised, crossover design. Cardiovascular variables and venous blood samples were measured prior to (control) and 2.5 h post supplement ingestion. Dietary NO3- supplementation increased plasma [NO3-] and plasma [nitrite] but had no effect on cyclic guanosine monophosphate (cGMP) concentration. Arterial stiffness markers improved following all NO3- doses, with no between-dose differences. However, endothelial function only improved following 400 mg (+3.07% compared to control) and aortic systolic BP only improved following 800 mg (-4 mmHg compared to control) dietary NO3- supplementation. Acute NO3- ingestion improved some cardiovascular risk factors, including arterial stiffness, macrovascular endothelial function and aortic systolic BP with different dose-response effects, but had no effect on brachial BP or plasma [cGMP]. These findings improve our understanding of NO3- supplementation and cardiovascular function in healthy adults.

Cardiovascular disease (CVD) is the primary cause of death and disability globally, accounting for nearly one in three fatalities. Implementing lifestyle and dietary changes can help lower blood pressure (BP) and reduce the risk of CVD. Notably, hypertension and CVD risk are more prevalent in Asian populations, a trend expected to rise with aging and increasing wealth among these communities. Many older adults are seeking natural approaches to enhance their health and quality of life, leading to a growing interest in food-based supplements like inorganic dietary nitrate (NO₃⁻). Nitrate is abundantly found in green leafy and root vegetables, such as beetroot. It serves as a precursor to nitric oxide (NO), a bioactive molecule with various roles in the body, including the regulation of neurotransmission, blood flow, and oxygen consumption. Research indicates that NO₃⁻ supplementation may offer benefits for health, cognitive function, and physiological performance in older adults. This paper will explore research supporting beetroot juice supplementation for reducing blood pressure and enhancing cognitive function in older people, its potential mechanisms of action, and practical applications..

The growing global demand for gluten-free products has positioned them as one of the most rapidly expanding trends in the food industry. Originally developed for individuals with celiac disease, gluten-free products have evolved into a wider market segment with significant development potential. In Indonesia, noodles represent an ideal medium for developing gluten-free food innovations due to their popularity and the availability of local raw materials. However, gluten-free noodles often face challenges related to poor texture and unbalanced nutritional composition, primarily due to the absence of gluten, which impairs dough elasticity and structural integrity. Beyond addressing these issues, gluten-free noodles can be further innovated as functional foods capable of enhancing VO₂Max. Emerging evidence suggests that the consumption of foods rich in the arginine amino acid, polyphenol and dietary nitrates can theoretically increase oxygen uptake, thereby enabling individuals to perform physical activities at elevated intensities and for extended durations without fatigue. Arginine and polyphenol is notably abundant in tempeh, a traditional Indonesian fermented soybean product, while nitrates are prevalent in leafy green vegetables such as spinach. By strategically selecting and combining raw materials with proven efficacy in improving gluten-free noodle quality, it is possible to develop products exhibiting favorable physicochemical and functional characteristics. In particular, the enrichment of arginine, polyphenol and nitrate contents holds promise due to their roles in nitric oxide synthesis and consequent enhancement of VO₂Max. The findings are expected to contribute to the advancement of nutritious and functional gluten free noodle products utilizing tempeh, a locally sourced Indonesian ingredients. This review not only advances gluten-free product innovation but also contributes to functional food development targeting improved physical performance.

Aim — Beetroot is a natural source of nitrate and nitrite ions and is known to provide various benefits in healthy volunteers. The present pilot clinical study was aimed to evaluate the effects of beetroot powder (BETA-NO●-BOOST) on serum lipids and inflammatory and metabolic markers in patients with early-stage arterial hypertension to assess feasibility of a subsequent expanded randomized crossover-controlled trial. Materials and Methods — The present study enrolled 22 male patients with early-stage AH treated for 7 days with an oral daily dose of 20 g BETA-NO●-BOOST equivalent to 650-700 mg of nitrate and nitrite ions (NOx). Blood samples were collected at baseline and at endpoint and used to assay serum levels of lipids and inflammatory and metabolic markers. Results — Total levels of cholesterol and alanine aminotransferase were decreased by 10% and 18.5% (p&lt;0.05), respectively, in all patients after 7-day use of beetroot powder. Hemoglobin concentration was decreased by 3.2% in 71% of the participants (p=0.001). The levels of C-reactive protein were decreased by 1.7-fold and leukocyte counts were decreased by 1.2x10⁹/L in 57% and 62% of the participants, respectively (p&lt;0.05). Levels of blood glucose, creatinine, aspartate aminotransferase, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and platelets were decreased in more than 50% of the participants. Conclusion — The results support feasibility of an expanded randomized crossover controlled study of BETA-NO●-BOOST, suggesting that consumption of dietary nitrate from natural plant sources may be associated with nitric oxide production to account for potential beneficial use of BETA-NO●-BOOST in various inflammatory and cardiovascular diseases.

High-altitude exposure poses significant health challenges to mountaineers, military personnel, travelers, and indigenous residents. Altitude-related illnesses encompass acute conditions such as acute mountain sickness (AMS), high-altitude pulmonary edema (HAPE), and high-altitude cerebral edema (HACE), and chronic manifestations like chronic mountain sickness (CMS). Hypobaric hypoxia induces oxidative stress and inflammatory cascades, causing alterations in multiple organ systems through co-related amplification mechanisms. Therefore, this review aims to systematically discuss the injury mechanisms and comprehensive intervention strategies involved in high-altitude diseases. In summary, these pathologies involve key damage pathways: oxidative stress activates inflammatory pathways through NF-κB and NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasomes; energy depletion impairs calcium homeostasis, leading to cellular calcium overload; mitochondrial dysfunction amplifies injury through mitochondrial permeability transition pore (mPTP) opening and apoptotic factor release. These mechanisms could be converged in organ-specific patterns-blood-brain barrier disruption in HACE, stress failure in HAPE, and right heart dysfunction in chronic exposure. Promising strategies include multi-level therapeutic approaches targeting oxygenation (supplemental oxygen, acetazolamide), specific pathway modulation (antioxidants, calcium channel blockers, HIF-1α regulators), and damage repair (glucocorticoids). Notably, functional foods show significant therapeutic potential: dietary nitrates (beetroot) enhance oxygen delivery, tea polyphenols and anthocyanins (black goji berry) provide antioxidant effects, and traditional herbal bioactives (astragaloside, ginsenosides) offer multi-targeted organ protection.

To investigate whether the association between the nitrite-generating capacity of the subgingival microbiome and early cardiometabolic risk biomarkers varies by dietary nitrate intake. Cross-sectional data from 668 participants (mean age 31 ± 9 years, 73% women) were analysed. Dietary nitrate intake was calculated from food frequency questionnaires. Subgingival 16S rRNA sequencing (Illumina, MiSeq) and PICRUSt2 estimated microbial genes. The Microbiome-Induced Nitric Oxide Enrichment Score (MINES) was calculated as a ratio of microbial gene abundances representing enhanced net capacity for NO generation. Adjusted multivariable linear models regressed cardiometabolic risk biomarkers (HbA1c, glucose, insulin, insulin resistance (HOMA-IR), blood pressure) on nitrate intake and MINES together with a MINES × nitrate intake interaction term. Mean nitrate intake was 190 ± 171 mg/day. Significant interactions of MINES and nitrate intake were observed for insulin and HOMA-IR (p < 0.05). Among participants with a low MINES, higher nitrate intake was associated with lower HOMA-IR (1.2 [1.1-1.4] vs. 1.5 [1.3-1.6]; p = 0.002), but levels were similar in those with high MINES (p = 0.84). A biomarker of higher microbial NO-generating capacity in subgingival plaque is associated with lower insulin and insulin resistance among individuals with lower dietary nitrate intake. Future trials evaluating the cardiometabolic benefits of nitrate-rich diets should incorporate measures of the entire oral microbiome.

Arterial hypertension (AH) is a highly prevalent, multifactorial cardiovascular condition characterized by endothelial dysfunction, increased oxidative stress, and impaired nitric oxide (NO) bioavailability. While pharmacological treatment is primarily directed toward blood pressure reduction, accumulating evidence indicates that several antihypertensive drug classes also confer antioxidant and vasculoprotective benefits. Concurrently, dietary intake of inorganic nitrate and nitrite has gained attention as an adjunctive approach to restore NO signaling and redox homeostasis. This narrative review summarizes current evidence regarding the antioxidant effects of major antihypertensive drug classes and examines the contribution of nitrate- and nitrite-rich diets to the modulation of oxidative stress and vascular dysfunction in AH. A systematic search of PubMed, EMBASE, Scopus, ScienceDirect, Web of Science, Google Scholar, and Food and Drug Administration (FDA) databases was performed for studies published between August and December 2025. Experimental and clinical investigations assessing oxidative stress markers, endothelial function, or NO-related outcomes in AH were selected following title and abstract screening and full-text evaluation. Available data indicate that angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, diuretics, β-blockers, and calcium channel blockers mitigate oxidative stress via mechanisms including NADPH oxidase suppression, decreased reactive oxygen species production, reinforcement of endogenous antioxidant systems, and restoration of endothelial NO bioavailability. Moreover, dietary nitrate and nitrite support vascular function through activation of the nitrate-nitrite-NO pathway. Combining nitrate- and antioxidant-rich dietary strategies with antihypertensive agents that lack inherent redox-modulating activity may enhance blood pressure control and lower cardiovascular risk. Nevertheless, well-designed long-term randomized clinical trials are needed to elucidate class-specific interactions and underlying redox mechanisms.

Increasing nitric oxide bioavailability via nitrate (NO3-) ingestion enhances muscle contractility, which may be due to phosphorylation of the regulatory light chain (RLC) of myosin. If so, there should be an interaction between NO3- supplementation and post-activation twitch potentiation, which acts via the same pathway. A double-blind, placebo-controlled, randomized crossover study was conducted to determine the influence of dietary NO3- on the contractile properties of the triceps brachii (60-70% fast-twitch, or type II) and triceps surae (60-70% slow-twitch, or type I) muscles of healthy young men (n=14). Participants were studied after acute ingestion of 2.2 mL/kg of beetroot juice either containing or lacking 200 µmol/kg of NO3-, with neuromuscular electrical stimulation used to determine muscle function. NO3- supplementation did not alter unpotentiated or potentiated peak twitch torque or the maximal rates of torque development or relaxation in either muscle group. On the other hand, NO3- ingestion resulted in significant changes in the torque-frequency relationship of both the triceps brachii (P=0.019) and the triceps surae (P<0.001). This was due to a leftward shift of this sigmoidal relationship in the triceps brachii, but a rightward shift in the triceps surae. We conclude that dietary NO3- has opposing effects on the contractile properties of fast and slow human muscles, which could be due to differential changes in Ca2+ sensitivity. However, potentiation was unaltered, suggesting that this occurs independently of changes in RLC phosphorylation. Additional research will be required to determine the underlying biochemical mechanisms.

This study aimed to assess whether dietary nitrate supplementation with resistance training (RT) augments gait performance and functional mobility in inactive middle-aged and older adults. We hypothesized that combining nitrate-rich beetroot juice (BRJ) with RT would yield improvements in gait and functional mobility compared to RT with nitrate-depleted beetroot juice placebo (PLA) supplementation. In this 12-week, randomized, double-blind, placebo-controlled pilot trial, 28 healthy, inactive adults (56 ± 7years) were assigned to either a BRJ (~ 12.8mmol nitrate/day) or PLA group while completing a supervised, full-body RT program (2×/week). Pre- and post-intervention assessments included the instrumented stand and walk (iSAW), 6-min walk test (i6MWT), and timed up and go (iTUG) tests. Supplement adherence, training compliance, and volume were equivalent between groups. ANCOVA analyses controlling baseline values revealed significant between-group differences favoring the BRJ group for gait speed (adjusted means: 1.38 vs 1.27m/s, p = .010), stride length (p < .001), and iTUG duration (p < .05). Within-group analyses confirmed that the BRJ group experienced significant improvements in gait speed (p < 0.001) and iTUG duration (p < 0.05), while the PLA group showed no functional changes, indicating that 12weeks of RT alone was insufficient to improve functional mobility in our sample despite equivalent training responses (p > .05). In our middle-aged sample, supplementing dietary nitrate alongside RT led to clinically meaningful improvements in functional mobility during self-selected conditions, exceeding the gains from 12weeks of twice-weekly RT alone. Preliminary descriptive analyses revealed sex-specific group-level differences that might suggest emerging trends. Although no inferential statistics were conducted, the patterns provide potential directions for future research investigating the effects of RT in middle-aged adults.

Background/Objectives: Dietary inorganic nitrate (NO3−), primarily sourced from vegetables such as beetroot, has been shown to enhance nitric oxide (NO) bioavailability, with emerging evidence suggesting its potential to modulate autonomic function. However, the effects of NO3− supplementation on cardiac autonomic recovery post-exercise in hypertensive postmenopausal women remain poorly understood. Using data from a previously conducted randomised controlled trial, this study investigated the effects of acute (800 mg) and seven-day (400 mg/day) beetroot juice NO3− supplementation on ultra-short-term post-exercise cardiac parasympathetic recovery in hypertensive older women. Methods: In a triple-blind, placebo-controlled crossover design, fourteen postmenopausal women (59 ± 4 y) with hypertension completed two intervention arms (NO3− and placebo). Ultra-short-term heart rate variability (HRV) indices (SDNN, RMSSD, HF) were assessed across 5 min post-exercise recovery using 60 s windows. Plasma NO2− and NO3− concentrations were measured via chemiluminescence. Results: Both acute and seven-day NO3− supplementation significantly increased plasma NO2− and NO3− concentrations compared to placebo (p < 0.001). Cardiac vagal recovery, assessed via SDNN and RMSSD, was significantly enhanced in both conditions, with greater and more sustained improvements observed after the seven-day protocol. HF power was significantly higher, but only after seven-day supplementation (p = 0.009). Conclusions: Inorganic NO3− supplementation enhances post-exercise cardiac parasympathetic reactivation in hypertensive postmenopausal women. Notably, the seven-day intake (400 mg/day) protocol elicited superior autonomic benefits compared to an acute high dose. These findings highlight the potential of NO3− as a non-pharmacological strategy for improving cardiovascular autonomic recovery in high-risk populations.

Nitric oxide (NO) is essential for maintaining normal cardiovascular function, and accumulating evidence suggests that its diminished bioavailability contributes to endothelial dysfunction, vascular stiffening, and impaired cardiac performance - hallmarks of cardiovascular aging. This review posits that reduced NO bioavailability with age stems from impaired endothelial and neuronal NO synthase activity, increased oxidative stress, and metabolic shifts that drive cardiovascular decline. We further discuss emerging research which highlights potential interventions, including dietary nitrate supplementation, caloric restriction, and exercise, that may restore NO signaling and counteract age-related cardiovascular dysfunction. These findings underscore the growing recognition of NO as a key regulator of cardiovascular aging and a promising therapeutic target. Addressing NO-related deficits could open new avenues for preventing and treating age-associated cardiovascular diseases, reshaping strategies for promoting healthy aging and longevity.

Alzheimer's disease (AD), the leading cause of dementia, has limited treatment options despite extensive pharmacological research. This has increased interest in dietary strategies that act across multiple pathological mechanisms. Beetroot (Beta vulgaris), known for its cardiovascular and metabolic benefits, contains a distinctive combination of bioactive compounds including inorganic nitrate, betalains, and polyphenols. Together these constituents influence vascular function, oxidative stress, mitochondrial efficiency, inflammation, and the microbiota. Previous reviews have typically focused on dietary nitrate in dementia prevention or have examined nitrate and betalains separately. In contrast, this review synthesises evidence on beetroot as a combined neuroprotective food. Preclinical data indicate that beetroot and its key constituents enhance antioxidant defences, support neuronal bioenergetics, and modulate cholinergic and inflammatory pathways. Human studies further suggest that nitrate-rich beetroot can improve cerebral blood flow and vascular responsiveness, and that higher intakes of plant-derived nitrate are associated with reduced cognitive decline. However, findings are inconsistent, most trials are small and short in duration, and research directly involving people with AD is scarce. By integrating vascular, antioxidant, and microbiome perspectives, this review identifies beetroot as a promising yet underexplored dietary candidate for AD management. Further mechanistic studies and multidomain approaches combining metagenomics, biomarkers, neuroimaging, and cognitive outcomes are needed.