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Varietal Evolution and Quality in Durum Wheat (Triticum turgidum subsp. durum): from Traditional Populations to Modern Cultivars

by luciano

This work examines the varietal evolution of durum wheat, from traditional local populations (landraces) to modern cultivars, highlighting the relationship between genetic improvement, agricultural transformation, productivity, and grain quality.

In the earliest historical phase, durum wheat cultivation relied on genetically heterogeneous local populations, well adapted to specific environments but characterized by low yields and high phenotypic variability. With the advent of scientific plant breeding, between the late nineteenth and the first half of the twentieth century, these populations were progressively replaced by varieties obtained through the selection of pure lines. These new cultivars were more uniform and better suited to mechanization and to the requirements of the processing industry.

The document describes the main phases of durum wheat genetic improvement in Italy: from genealogical selection based on landraces (1920–1950), to the development of varieties derived from controlled crosses between Mediterranean and Syrian genotypes (1950s–1960s), and subsequently to more advanced approaches such as interspecific hybridization, induced mutagenesis, and the introduction of dwarfing genes (Rht) aimed at reducing plant height and increasing the harvest index.

Particular attention is given to the key role of historical cultivars such as Senatore Cappelli, which for decades represented the benchmark for both productivity and quality in Italian durum wheat, as well as to the later varieties that progressively replaced it due to higher yields and improved resistance to lodging and biotic stresses.

The work also emphasizes that, alongside productivity gains, agricultural intensification and the widespread adoption of genetically uniform cultivars have led to genetic erosion. This makes the conservation of germplasm, through both in situ and ex situ strategies, increasingly important. In conclusion, durum wheat breeding is presented as a dynamic process, closely linked to agronomic innovation, market demands, and the need to balance productivity, quality, and biodiversity conservation. Authors: Rosella Motzo, Francesco Giunta, Simonetta Fois. Coordinator: Prof. Mauro Deidda
Year: 2001. Co-funding body: Banco di Sardegna Foundation (note 1154/4135 of 12/18/2001)

Updates to date (key advances):

1) Reference genome del frumento duro (base per tutte le analisi moderne)
Title: Durum wheat genome highlights past domestication signatures and future improvement targets
Authors: Maccaferri, Harris, Twardziok, et al.
Year: 2019
DOI: 10.1038/s41588-019-0381-3 (PubMed)
Riassunto: Primo riferimento “chiave” con assemblaggio genomico del duro (cv. Svevo) e analisi di diversità/geni target: ha abilitato GWAS più robuste, identificazione di regioni selezionate durante domesticazione/miglioramento e nuovi bersagli per qualità e resa.

2) Speed breeding applicato specificamente al frumento duro (accelerare generazioni + selezione multi-tratto)
Title: Speed breeding for multiple quantitative traits in durum wheat
Authors: Alahmad et al.
Year: 2018
DOI: 10.1186/s13007-018-0302-y (PubMed)
Riassunto: Protocollo sperimentale per velocizzare cicli generazionali e fare selezione precoce su più caratteri quantitativi (non solo uno), utile per accelerare pyramiding di tratti (resa, fenologia, architettura, ecc.).

3) Genomic selection + GWAS in frumento duro (metodi moderni per prevedere resa/qualità)
Title: Genetic dissection of agronomic and quality traits based on association mapping and genomic selection approaches in durum wheat grown in Southern Spain
Authors: Mérida-García et al.
Year: 2019
DOI: 10.1371/journal.pone.0211718 (PLOS)
Riassunto: Combina association mapping (GWAS) e genomic selection su tratti agronomici e qualitativi: è un esempio “completo” di pipeline moderna (scoperta di loci + predizione genomica per selezione).

4) Fenotipizzazione ad alta capacità (iperspettrale) per stress caldo/siccità + genetica della resa
Title: High-throughput phenotyping using hyperspectral indicators supports the genetic dissection of yield in durum wheat grown under heat and drought stress
Authors: Mérida-García et al.
Year: 2024
DOI: 10.3389/fpls.2024.1470520 (PubMed)
Riassunto: Porta “novità” sul metodo: usa indicatori iperspettrali come proxy fisiologici per analizzare resa sotto stress, collegandoli alla genetica (utile per selezione in ambienti climate-stress).

5) Genomica + partecipazione agricoltori (local adaptation, “participatory genomics”)
Title: Genomics-driven breeding for local adaptation of durum wheat…
Authors: Gesesse et al.
Year: 2023
DOI: (indicizzato su PubMed; verificabile nella scheda articolo) (PubMed)
Riassunto: Integra dati genomici con selezione/valutazioni degli agricoltori (contesti low-input): introduce un approccio più “real-world” per migliorare adattamento locale e adozione varietale.

6) Dalle landraces agli aplotipi (integrazione “genomic + phenomic” per adattamento climatico)
Title: From landraces to haplotypes, exploiting a genomic and phenomic…
Authors: Palermo et al.
Year: 2024
DOI: (presente nella pagina articolo ScienceDirect) (ScienceDirect)
Riassunto: Usa tecniche avanzate per caratterizzare landraces (es. SSD, dati genomici + fenomici) per trovare materiale “ponte” tra varietà commerciali e resilienza a caldo/siccità.

7) CRISPR in frumento (dimostrazioni di editing multi-gene con impatto su qualità/sicurezza alimentare)
Title: CRISPR-Cas9 Multiplex Editing of the α-Amylase/Trypsin Inhibitor Genes…
Authors: Camerlengo et al.
Year: 2020
DOI: 10.3389/fsufs.2020.00104 (Frontiers)
Riassunto: Esempio di multiplex editing (più geni insieme) per ridurre componenti proteiche potenzialmente problematiche; dimostra velocità/precisione dell’editing rispetto al breeding convenzionale.

8) Protocolli/metodologia CRISPR per wheat (come “toolbox” operativo)
Title: CRISPR-Cas9 Based Genome Editing in Wheat
Authors: Smedley et al.
Year: 2021
DOI: 10.1002/cpz1.65 (currentprotocols.onlinelibrary.wiley.com)
Riassunto: Non è solo “risultato”, ma un riferimento pratico: design sgRNA, costrutti, workflow sperimentale per implementare CRISPR in wheat.

9) Review “stato dell’arte” specifica su duro (trend e metodi emergenti)
Title: Future of durum wheat research and breeding: Insights from early career researchers
Authors: Haugrud et al.
Year: 2024
DOI: 10.1002/tpg2.20453 (acsess.onlinelibrary.wiley.com)
Riassunto: Sintesi aggiornata su dove sta andando la ricerca: nuove fonti di variabilità, genomica, fenomica, breeding per stress e qualità, e priorità future.

 

 

 

 

 

 

 

 

The Role of Water in Reducing Low-Grade Inflammation

by luciano

(The Role of Water in Reducing Low-Grade Inflammation and Anti-Inflammatory Foods in Maintaining Physiological Homeostasis*)

(with references to the scientific section)

See: Practical vademecum (Why water helps extinguish inflammation)

1. Introduction
Low-grade inflammation is a condition of chronic and mild activation of the immune system, associated with numerous metabolic and pathological conditions, including obesity, metabolic syndrome, insulin resistance, and gut dysbiosis (studiolendaroeflorio.com). Emerging scientific evidence indicates that chronic dehydration and suboptimal dietary patterns are factors that not only affect metabolic function but also contribute to the persistence of a subclinical inflammatory state (PMC).

2. Water as an Essential Nutrient: Physiology and Hydric Homeostasis
Water is the most abundant component of the human body, accounting for approximately 50–65% of body weight in healthy adults (gabrielepelizza.com). This molecule is not merely a solvent but actively participates in metabolic processes, nutrient transport, waste elimination, regulation of cellular volume, and maintenance of body temperature (PMC).

2.1. Transport and Elimination of Metabolic Substances
Water forms the fluid medium in which the following processes occur:

transport of essential nutrients to cells,
mobilization and elimination of metabolic catabolic by-products,
transport of pro-inflammatory mediators to excretory organs (kidneys, liver).
Adequate plasma water volume facilitates glomerular filtration and enhances the kidneys’ ability to eliminate metabolic residues that may stimulate inflammation when accumulated (PMC).

2.2. Hydration and Systemic Inflammation
Studies investigating the effects of water restriction have shown that dehydration can contribute to metabolic imbalances and alterations in cellular function that promote systemic inflammatory responses (PMC).

A recent study on the gut microbiota indicates that water restriction disrupts intestinal homeostasis, leading to a reduction in local immune elements such as Th17 cells—key regulators of mucosal inflammation—suggesting a link between hydration status and immune response (ScienceDirect).

3. Specific Mechanisms Through Which Water Reduces Inflammation
3.1. Improved Circulation and Lymphatic Drainage
Adequate hydration maintains lower blood viscosity, improving fluidity and enhancing the transport of oxygen and nutrients to tissues while facilitating the removal of pro-inflammatory metabolites. Although no randomized controlled trials (RCTs) are specifically dedicated to this mechanism, basic cardiovascular physiology clearly describes these effects.

3.2. Effects on the Gut Microbiota
As previously mentioned, recent studies show that limited access to water alters the gut microbiota and reduces key immune cell populations in the colon, highlighting a connection between hydration and intestinal immune regulation (ScienceDirect).

3.3. Hydration and Reduction of Oxidative Stress
Adequate water intake is associated with lower circulating concentrations of free radicals and may reduce systemic inflammatory responses related to oxidative stress, at least indirectly through improved metabolic homeostasis and normal cellular function (limited but suggestive evidence from general clinical reviews) (Prevention).

4. Water as a Support to Immune Response
Hydration also affects general immune parameters. Preliminary evidence suggests that adequate water intake contributes to optimal immune system function, particularly under conditions of physiological stress or high antigenic load (ResearchGate).

5. Anti-Inflammatory Nutrition: Role of Specific Nutrients
An anti-inflammatory diet includes foods rich in:

Polyphenols (berries, green tea),
Omega-3 fatty acids (fatty fish, flaxseeds),
Antioxidants (colorful vegetables, spices such as turmeric and ginger),
Dietary fiber (legumes, vegetables), which nourish the gut microbiota.
These components are associated with measurable reductions in pro-inflammatory mediators such as IL-6 and TNF-α in several observational and clinical studies, although the strength of evidence for specific nutrients varies from moderate to weak or preliminary (e.g., polyphenols) (ScienceDirect).

6. Synergy Between Hydration and Anti-Inflammatory Nutrition
The synergy between water intake and anti-inflammatory nutrition is based on two main physiological mechanisms:

6.1. Nutrient Absorption and Bioavailability
Water is the medium in which:

digestion occurs,
chylomicrons are formed and nutrients are transported,
bioactive anti-inflammatory compounds are absorbed.
A well-hydrated intestine promotes optimal transit time, reduces pathological fiber fermentation, and supports a more balanced microbiota, which in turn produces anti-inflammatory metabolites such as butyrate (ScienceDirect).

6.2. Elimination of Inflammatory By-Products
Hydration facilitates the elimination of pro-inflammatory molecules through:

urine (water-soluble metabolites),
bile (certain lipids and metabolic products),
thereby improving the efficiency of the body’s homeostatic response.

7. Clinical and Practical Applications
Although no unified guidelines based on robust RCT evidence exist for anti-inflammatory hydration protocols, physiological principles and emerging evidence suggest that optimal hydration combined with an anti-inflammatory diet may help maintain a favorable physiological state, reduce low-grade inflammation, and support immune homeostasis.

8. Conclusions
Water is a physiologically active element in the modulation of inflammation and maintenance of health, not merely a passive solvent. Its role extends from fluid homeostasis and nutrient transport to regulation of the gut microbiota and immune support.
When combined with a diet rich in anti-inflammatory foods, water acts synergistically to:

improve nutrient absorption,
facilitate the removal of inflammatory mediators,
optimize gut microbiota composition,
support a balanced immune response.

These mechanisms are supported by studies in physiology, microbiology, and emerging research on the effects of hydration on immune modulation.

*Homeostasis is the ability of living organisms to maintain a constant internal environment (temperature, pH, blood sugar, etc.) by self-regulating, despite external variations.

In-Depth Focus: Carbonated Water and Digestion
✅ Potential Benefits
May stimulate digestion
Carbon dioxide (CO₂) mildly stimulates the gastric mucosa, increasing gastric juice secretion.
Helpful in slow digestion
Some individuals find it beneficial after heavy meals.
Promotes satiety
It may help reduce food intake in certain dietary regimens.
⚠️ Potential Discomforts
Bloating and gas
CO₂ is gas and may cause abdominal distension and belching.
May worsen reflux or gastritis
In individuals with gastroesophageal reflux or sensitive stomachs, symptoms may worsen.
Not ideal for irritable bowel syndrome (IBS)
Gas can increase pain and abdominal distension.
Carbonated vs Still Water
Hydration level → equivalent
Digestive tolerance → still water is more neutral and generally better tolerated
General health → no issues if consumed in moderation
How Much to Drink?
For healthy individuals:

Suitable for daily consumption, preferably alternating with still water
Best avoided during meals in those prone to bloating
Summary
Carbonated water is not harmful to health but can influence digestion: it may facilitate digestion in some individuals while causing bloating or gastric discomfort in others. For this reason, alternating it with still water and tailoring consumption to individual digestive tolerance is recommended.

Selected References
Allen, M.D. et al. Suboptimal hydration remodels metabolism…, 2019 (PMC)
Sato, K. et al. Sufficient water intake maintains the gut microbiota…, 2024 (ScienceDirect)
Popkin, B.M. et al. Water, Hydration and Health, 2010 (PMC)
Özkaya, İ. & Yıldız, M. Effect of water consumption on the immune system…, 2021 (ResearchGate)
Clinical trial with anti-inflammatory implications (methodological limitations; further studies needed) (jamanetwork.com)

Practical vademecum (Why water helps extinguish inflammation)

by luciano

(with references to the scientific section)

Why water helps extinguish inflammation

1️⃣ It dilutes and facilitates the elimination of inflammatory substances
(→ see Sec. 2.1; Sec. 3.1)

During an inflammatory state, the body produces:
cytokines
inflammatory mediators
metabolic waste products

Water:
increases plasma volume
facilitates renal filtration function
supports hepatic detoxification
accelerates elimination via urine and bile

⚠️ In conditions of dehydration, these molecules remain more concentrated → persistent inflammation.

2️⃣ Improves circulation and tissue “cleansing”
(→ see Sec. 3.1)

Adequate hydration makes the blood:
less viscous
more fluid
more efficient in transporting oxygen and nutrients

This allows cells to:
repair themselves more effectively
dispose of inflammatory by-products more rapidly

3️⃣ Supports the lymphatic system
(→ see Sec. 3.1)

The lymphatic system is a drainage network for chronic inflammation.
Its function depends critically on the availability of water.

In the case of insufficient water intake:
lymph stagnates
toxins remain in the tissues
low-grade inflammation is amplified

4️⃣ Regulates intestinal balance
(→ see Sec. 3.2; Sec. 6.1)

Low-grade inflammation is frequently associated with:
constipation
intestinal dysbiosis
increased intestinal permeability

Water:
improves intestinal transit
promotes the elimination of endotoxins
reduces systemic inflammatory stimulus

The gut acts as a central hub of systemic inflammation.

5️⃣ Reduces physiological stress
(→ see Sec. 3.3; Sec. 4)

Dehydration is interpreted by the body as biological stress.

Physiological consequences:
increase in cortisol
greater production of inflammatory mediators

Drinking adequately = stress reduction → inflammation reduction.

Effects that go beyond low-grade inflammation
(→ see Sec. 7)

Adequate hydration also contributes to:
reduction of joint and muscle pain
better post-workout recovery
decrease in recurrent headaches
reduction of chronic fatigue
improvement of inflammatory skin conditions

Key concept
(→ see Conclusions)

Water is not a direct anti-inflammatory,
but the necessary condition for the body
to be able to autonomously switch off inflammation.

What makes water even more effective
(→ see Sec. 6; Sec. 7)

drink regularly throughout the day
avoid concentrating all intake in a few moments
combine with minerals, especially in case of sweating
pair it with an anti-inflammatory diet
(vegetables, omega-3s, fiber)

Why water + anti-inflammatory foods work better together

1️⃣ Water is the transport medium for anti-inflammatory nutrients
(→ see Sec. 6.1)

Anti-inflammatory foods provide:
polyphenols
antioxidants
minerals
omega-3s
fiber

In the absence of sufficient water:
intestinal absorption is reduced
blood transport slows down
cellular effectiveness decreases

High nutritional quality, low biological yield.

2️⃣ Fiber + water = calm gut = less inflammation
(→ see Sec. 6.1; Sec. 3.2)

Fiber:
nourishes the microbiota
contributes to the reduction of intestinal inflammation

⚠️ Fiber without water:
slows transit
ferments dysfunctionally
can increase bloating and intestinal stress

Water + fiber = endotoxin elimination → ↓ systemic inflammation.

3️⃣ Water attenuates the post-prandial inflammatory response
(→ see Sec. 6.2)

Even a balanced meal generates:
metabolic heat
temporary by-products

Drinking water:
dilutes metabolites
supports liver and kidneys
reduces the post-meal inflammatory response

Key pairings: what to eat + how to drink
(→ see Sec. 5; Sec. 6)

Healthy fats
(extra virgin olive oil, avocado, nuts)
✔️ Anti-inflammatory
➕ Water:
improves blood fluidity
facilitates the action of omega-3s
Prefer intake before the meal.

Polyphenols
(berries, green tea, unsweetened cocoa)
✔️ Neutralize free radicals
➕ Water:
promotes cellular distribution
accelerates elimination of neutralized radicals

Bitter and cruciferous vegetables
✔️ Support liver function
➕ Water:
stimulates bile production
promotes hepatic detoxification

Anti-inflammatory spices
(turmeric, ginger)
✔️ Inflammatory modulators
➕ Water:
improves bioavailability
reduces gastric irritation
Also ideal in warm water or herbal teas.

⏰ When to drink to enhance the anti-inflammatory effect
(→ see Sec. 7)

upon waking → intestinal activation and drainage
between meals → support for nutrient transport
before meals → modulation of the inflammatory response
❌ avoid large amounts during meals

Sparkling water

Slightly stimulates digestion and may increase satiety.
In some people, it facilitates slow digestion.
However, it can cause bloating and belching.
To be limited in cases of reflux, gastritis, or irritable bowel syndrome.
It hydrates as much as still water, but is less neutral for the stomach.
Recommended in moderation and alternated with still water (→ see Sec. 8)

Final key phrase

Anti-inflammatory foods extinguish the fire.
Water carries away the ash.
Without water, the ash remains.

Oxidative Stress: What It Is, Why It Arises, What It Causes, How to Reduce It

by luciano

Highlight

Oxidative stress is a biological condition characterized by an imbalance between the production of reactive oxygen species (ROS) and the body’s ability to neutralize them through antioxidant systems.
When this imbalance persists over time, the risk of molecular damage, cellular dysfunction, and the development of numerous chronic diseases increases.

What Is Oxidative Stress

Oxidative stress occurs when ROS production exceeds the capacity of endogenous and exogenous antioxidant systems to keep them within a physiological range.

ROS include:

  • true free radicals (e.g., superoxide O₂•⁻, hydroxyl radical •OH)

  • non-radical reactive species (e.g., hydrogen peroxide H₂O₂)

ROS are continuously produced during cellular metabolism, particularly in the mitochondrial electron transport chain.

BOX — ROS does not mean “toxic”
ROS are not intrinsically harmful. At low concentrations they perform essential functions:

  • cellular signaling

  • immune defense

  • adaptation to physical exercise

They become pathological only when they exceed redox control capacity.

Where ROS Come From

Endogenous production

  • mitochondrial respiration

  • nutrient metabolism

  • immune system activity

  • metabolism of drugs and xenobiotics

Factors that increase production

  • mitochondrial dysfunction

  • altered circadian rhythms

  • chronic psychophysiological stress

  • hyperglycemia and lipotoxicity

  • smoking, pollutants, UV radiation

  • unbalanced diet

What Is Redox Imbalance

Under normal conditions, the body possesses:

  • antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase)

  • non-enzymatic antioxidants (glutathione, vitamin C, vitamin E, polyphenols)

Oxidative stress arises when ROS production exceeds these defenses.

What Oxidative Stress Damages

DNA

  • oxidation of bases (e.g., 8-oxo-guanine)

  • strand breaks

  • mutations if repair is incomplete

Proteins

  • oxidation of amino acid residues

  • loss of three-dimensional structure

  • reduced enzymatic activity

Membrane lipids

  • lipid peroxidation

  • loss of fluidity

  • increased membrane permeability

Long-Term Consequences

The accumulation of oxidative damage is associated with:

  • cellular aging

  • cardiovascular diseases

  • type 2 diabetes

  • neurodegenerative diseases (Alzheimer’s, Parkinson’s)

  • increased cancer risk

Oxidative stress is not the only cause of these conditions, but it represents an important contributing biological factor.

BOX — Relationship between oxidative stress and inflammation
Oxidative damage is a direct mechanism.
Inflammation is a response to damage that, once established, can amplify it.
A vicious cycle often develops:

ROS → molecular damage → inflammatory activation → production of additional ROS → further damage

How to Reduce Oxidative Stress

The goal is not to eliminate ROS, but to restore redox balance.

Nutrition

  • high intake of vegetables

  • adequate protein intake

  • control of refined carbohydrates

  • reduction of oxidized and ultra-processed foods

Physical activity

  • moderate and regular

  • avoids both inactivity and overtraining

Sleep and biological rhythms

  • sufficient sleep

  • exposure to natural daylight

  • reduction of evening artificial light

Stress management

  • relaxation techniques

  • sustainable workload

Lifestyle

  • smoking cessation

  • alcohol moderation

BOX — Antioxidants: key point
The main objective is not to consume large amounts of exogenous antioxidants, but to strengthen endogenous antioxidant systems (e.g., via Nrf2).
Indiscriminate high-dose supplementation is not always beneficial.

Final Message

Oxidative stress represents a functional imbalance of the cellular redox system.
Its prevention requires an integrated approach addressing nutrition, movement, sleep, stress, and mitochondrial function.

RELATED ARTICLES published in:

(In-depth of “Oxidative Stress: What It Is, Why It Arises, What It Causes, How to Reduce It”)

  1. Mitochondria and oxidative stress

    • why they are the main source of ROS

    • mitochondrial dysfunction and chronic diseases

  2. Circadian rhythm and redox metabolism

    • sleep, light, meal timing

  3. Exercise, hormesis, and Nrf2

    • why physical activity is “antioxidant training”

  4. Low-grade chronic inflammation

    • what it is

    • relationship with oxidative stress

  5. Biomarkers of oxidative stress

    • F2-isoprostanes

    • 8-OHdG

    • GSH/GSSG

    • hs-CRP

    • integrated interpretation

  6. Antioxidant supplements: when they truly help

    • limits

    • risks of high doses

    • personalized approach

ESSENTIAL BIBLIOGRAPHY

Birben E. et al., Oxidative Stress and Antioxidant Defense, 2012
Betteridge DJ., What is oxidative stress?, 2000
Roberts LJ & Milne GL., Isoprostanes as markers of lipid peroxidation, 2000
Ristow M. et al., Antioxidants prevent health-promoting effects of exercise, 2009
Powers SK., Exercise-induced activation of Nrf2 signaling, 2024

In-Depth: “Oxidative Stress: What It Is, Why It Arises, What It Causes, How to Reduce It”

by luciano

✅ RELATED ARTICLE 1
Mitochondria and Oxidative Stress
Highlight
Mitochondria are the main source of ROS in the body and at the same time one of the primary targets of oxidative damage.

Their efficiency largely determines the level of cellular oxidative stress.

What mitochondria do
Produce ATP via oxidative phosphorylation
Regulate apoptosis
Participate in cellular signaling
Regulate nutrient metabolism
During energy production, a small fraction of electrons escapes from the respiratory chain, forming superoxide.

Why mitochondria produce ROS
In the electron transport chain:
O₂ + electron → O₂•⁻

This is a physiological and unavoidable event.

BOX — Physiological production
A moderate production of mitochondrial ROS is necessary for:

adaptive signaling
Nrf2 activation
mitochondrial biogenesis
What is mitochondrial dysfunction
A condition in which:

ATP production decreases
electron leakage increases
ROS production increases
A vicious cycle is created:

Inefficient mitochondrion → more ROS → mitochondrial damage → even less efficient mitochondrion

Factors that damage mitochondria
chronic hyperglycemia
excess oxidized fats
inflammation
toxins
micronutrient deficiencies
sleep deprivation
Mitochondria and chronic diseases
Mitochondrial dysfunction observed in:

type 2 diabetes
cardiovascular disease
neurodegeneration
sarcopenia
aging
How to improve mitochondrial function
Nutrition

adequate protein intake
micronutrients (B vitamins, iron, copper, magnesium)
polyphenols
Physical activity

aerobic exercise
resistance training
Sleep

regularity
7–9 hours
Stress

reduction of chronic load
BOX — Key concept
Oxidative stress is not reduced by “turning off ROS.”
It is reduced by making mitochondria more efficient.

Conclusion
The mitochondrion is the central hub of redox metabolism.
Protecting mitochondrial function means acting upstream on oxidative stress.

✅ RELATED ARTICLE 2
Circadian Rhythm and Oxidative Stress
Highlight
The circadian rhythm coordinates the expression of genes involved in metabolism, energy production, and antioxidant systems.
When this timing system is altered, ROS production increases and the capacity to neutralize them decreases, promoting chronic oxidative stress.

What is the circadian rhythm
A biological timing system of about 24 hours that regulates:

sleep–wake cycle
hormone secretion
energy metabolism
body temperature
cellular repair activity
The main control center is the suprachiasmatic nucleus of the hypothalamus, mainly synchronized by light.

Central and peripheral clocks
There are:

one central clock (brain)
peripheral clocks (liver, muscle, pancreas, adipose tissue, heart)
These clocks regulate the temporal expression of thousands of metabolic genes.

BOX — Key concept
Not only what you do, but also when you do it influences redox metabolism.

Link between circadian rhythm and antioxidant systems
Many antioxidant enzymes show circadian oscillations:

superoxide dismutase (SOD)
catalase
glutathione peroxidase
Glutathione synthesis also follows a daily rhythm.
If rhythm is disturbed, these oscillations flatten → lower antioxidant defenses.

Circadian rhythm and mitochondria
The biological clock regulates:

mitochondrial biogenesis
fusion/fission dynamics
respiratory chain efficiency
Circadian misalignment → less efficient mitochondria → greater electron leakage → more ROS.

What disrupts circadian rhythm
evening artificial light
nighttime screen exposure
shift work
insufficient sleep
irregular or nighttime meals
social jet lag
Biological effects of misalignment
Chronic misalignment causes:

increased ROS production
reduced antioxidant activity
increased inflammation
altered glucose and lipid metabolism
BOX — Simplified mechanism
Altered rhythm → inefficient mitochondria → ↑ ROS
Altered rhythm → ↓ antioxidant enzymes
Result: oxidative stress

Circadian rhythm and chronic diseases
Associated with higher risk of:

obesity
type 2 diabetes
metabolic syndrome
cardiovascular disease
cognitive decline
Partly through increased systemic oxidative stress.

Sleep: the main redox “reset”
During sleep:

brain metabolism decreases
antioxidant activity increases
DNA repair systems activate
mitochondrial efficiency improves
Sleep deprivation → measurable increase in oxidative stress markers after only a few nights.

Meal timing and oxidative stress
Eating at biologically inappropriate times:

worsens glycemic control
increases mitochondrial ROS production
promotes lipotoxicity
An eating window aligned with the light–dark cycle improves redox balance.

How to protect circadian rhythm
Light

natural light in the morning
reduced blue light in the evening
Sleep

regular schedule
adequate duration
Meals

consistent timing
avoid large nighttime meals
Physical activity

preferably during daytime
BOX — Key concept
Without a functional circadian rhythm, even a perfect diet and good supplements have limited effectiveness on oxidative stress.

Integration with other pillars
Circadian rhythm acts in synergy with:

mitochondrial function
exercise
stress management
Protecting rhythm is a primary lever in oxidative stress prevention.

Conclusion
The circadian rhythm is a fundamental regulator of redox balance.
Its disruption promotes both increased ROS production and reduced antioxidant defenses, creating conditions for chronic oxidative stress.
Preserving the light–dark rhythm is one of the most powerful and underestimated interventions for cellular health.

✅ RELATED ARTICLE 3
Exercise, Hormesis, and Nrf2: Why Movement Reduces Oxidative Stress
Highlight
Exercise transiently increases ROS production, but this controlled stimulus activates powerful adaptive mechanisms that enhance endogenous antioxidant defenses.
This phenomenon is known as hormesis and is largely mediated by the transcription factor Nrf2.

The exercise paradox
During physical activity:

oxygen consumption increases
mitochondrial electron flux increases
ROS production temporarily increases
Yet, in the long term, regularly trained individuals show lower basal oxidative stress.

BOX — Apparent paradox
Exercise produces ROS, but training reduces chronic oxidative stress.

What is hormesis
Hormesis is a biological principle whereby:
A small stress activates protective adaptations that make the organism more resistant.

In exercise:
ROS transients → signal → adaptation → increased antioxidant capacity

Nrf2: the master regulator
Nrf2 (Nuclear factor erythroid 2–related factor 2) is a transcription factor that:

senses oxidative stress signals
migrates to the nucleus
activates antioxidant gene expression
Genes regulated by Nrf2 include:

glutathione synthase
glutathione peroxidase
superoxide dismutase
catalase
phase II detoxification enzymes
BOX — Key concept
Nrf2 does not neutralize ROS directly.
It increases the cell’s ability to defend itself.

What happens with regular training
Over time:

glutathione content increases
antioxidant enzymes increase
mitochondrial efficiency improves
basal ROS production decreases
Result: greater redox resilience.

Types of exercise and redox response
Aerobic

brisk walking
moderate running
cycling
Promotes:
mitochondrial biogenesis
Nrf2 activation
Strength

weights
bodyweight training
Promotes:
increased muscle mass
improved glucose metabolism
lower resting ROS production
HIIT

strong adaptive stimulus
useful if properly dosed
When exercise becomes harmful
Excess volume or intensity without recovery:

persistently elevated ROS
reduced immune function
increased inflammation
BOX — Optimal zone
Too little exercise → oxidative stress
Too much exercise → oxidative stress
Moderate dose → protective adaptation

Antioxidants and exercise: caution
High-dose vitamin C and E supplementation:

may blunt Nrf2 activation
may reduce some metabolic benefits of training
Integration with lifestyle
Exercise protection is maximal when combined with:

adequate sleep
balanced nutrition
stress management
Exercise as “medicine”
Physical activity:

reduces cardiovascular risk
improves insulin sensitivity
protects the brain
slows biological aging
Largely through improved redox balance.

BOX — Final key concept
Exercise does not reduce oxidative stress by eliminating ROS,
but by making the organism better able to handle them.

Conclusion
Physical exercise is one of the most powerful physiological tools for controlling oxidative stress.
Through transient ROS increases, it activates Nrf2 and triggers adaptations that strengthen endogenous antioxidant defenses, improving long-term cellular health.

✅ RELATED ARTICLE 4
Low-Grade Chronic Inflammation and Oxidative Stress
Highlight
Low-grade chronic inflammation is a persistent state of mild immune activation, often asymptomatic, that contributes to the development of many chronic diseases.
It is tightly intertwined with oxidative stress through a mutually amplifying circuit.

What is low-grade chronic inflammation
Unlike acute inflammation (rapid and resolving), it is:

persistent
systemic
low intensity
It does not cause obvious clinical signs but progressively alters tissue physiology.

Difference between acute and chronic inflammation
Acute inflammation

protective response
short duration
promotes healing
Low-grade chronic inflammation

continuous activation
lack of resolution
promotes tissue damage
BOX — Key concept
The problem is not inflammation itself, but its persistence.

Link with oxidative stress
Oxidative stress and inflammation form a bidirectional loop:

ROS activate inflammatory pathways
inflammatory cells produce ROS
BOX — Simplified circuit
ROS → cellular damage → inflammation → ROS production → further damage

Molecular mechanism
ROS activate transcription factors such as:

NF-κB
AP-1
These induce production of:

IL-6
TNF-α
other pro-inflammatory cytokines
Cytokines in turn increase:

oxidase activity
mitochondrial ROS production
Oxidative damage as primary event
Molecular damage caused by ROS can occur:

in absence of immune cells
directly to DNA, lipids, proteins
Inflammation represents a secondary response to damage.

BOX — Crucial point
Oxidative stress can initiate damage.
Inflammation maintains it.

Chronic inflammation and metabolism
Low-grade inflammation:

reduces insulin sensitivity
promotes dysfunctional lipolysis
increases ROS production
Explaining links with:

type 2 diabetes
metabolic syndrome
visceral obesity
Chronic inflammation and target organs
Involved in:

atherosclerosis
fatty liver
neurodegeneration
sarcopenia
Main factors promoting chronic inflammation
caloric excess
ultra-processed diet
sedentary lifestyle
sleep deprivation
psychological stress
gut dysbiosis
How to reduce chronic inflammation
Diet

high nutrient density
fiber
unsaturated fats
Physical activity

regular
Sleep

7–9 hours
Stress management

relaxation practices
BOX — Key concept
Reducing chronic inflammation also reduces oxidative stress.

Integration with other pillars
Inflammation is modulated by:

mitochondrial function
circadian rhythm
physical exercise
No single intervention is sufficient.

Conclusion
Low-grade chronic inflammation and oxidative stress form an integrated system of biological damage amplification.
Interrupting this circuit requires a systemic approach acting on metabolism, lifestyle, and neuroendocrine regulation.

✅ RELATED ARTICLE 5
Biomarkers of Oxidative Stress: What to Measure and How to Interpret
Highlight
Oxidative stress cannot be evaluated with a single test.
A clinically meaningful assessment requires integration of biomarkers of oxidative damage, inflammation, antioxidant capacity, and metabolic context.

Why there is no “perfect marker”
Oxidative stress is a dynamic process involving:

ROS production
molecular damage
antioxidant response
repair
Each biomarker observes only one part.

BOX — Key concept
A panel is more informative than a single value.

1) Direct biomarkers of oxidative damage
F2-isoprostanes

Derived from non-enzymatic lipid peroxidation
Considered gold standard for lipid oxidative damage
Sample: plasma or urine
Interpretation:
High → high lipid oxidative stress
Malondialdehyde (MDA)

Lipid peroxidation product
More variable than isoprostanes
Interpretation:
Useful as orientative indicator
8-OHdG (8-hydroxy-2’-deoxyguanosine)

Marker of oxidative DNA damage
Urine or blood
Interpretation:
High → increased DNA oxidation
2) Antioxidant capacity biomarkers
Reduced glutathione (GSH) and GSH/GSSG ratio

Central redox parameter
Interpretation:
High ratio → good balance
Low ratio → oxidative stress
Total antioxidant capacity (TAC)

Global estimate of ROS-neutralizing ability
Low specificity
Interpretation:
Useful as complement
3) Inflammation-related biomarkers
hs-CRP

Integrated marker of systemic inflammation
Indicative values:
<1 mg/L → low CV risk
1–3 mg/L → intermediate risk
3 mg/L → high risk
IL-6, TNF-α

Pro-inflammatory cytokines
Mainly specialist use
4) Indirect metabolic biomarkers
Glucose, insulin, HOMA-IR
Triglycerides, oxLDL
Ferritin
BOX — Key concept
Metabolic alterations are often the main source of chronic oxidative stress.

5) Advanced mitochondrial biomarkers
Resting lactate
Lactate/pyruvate ratio
CoQ10
Useful in specialist settings.

6) Minimal practical panel
hs-CRP
F2-isoprostanes or MDA
8-OHdG
GSH/GSSG
Glucose + insulin
7) Integrated interpretation example
hs-CRP ↑
MDA ↑
GSH/GSSG ↓

Indicates:

active oxidative stress
associated inflammation
reduced defenses
8) Temporal changes after intervention
Improve first:

GSH/GSSG
hs-CRP
Later:

MDA / F2-isoprostanes
Slowest:

8-OHdG
BOX — Typical sequence
Protection rises → damage falls → DNA improves

9) Common errors
Relying on one marker
Using TAC alone
Interpreting without clinical context
Conclusion
Assessment of oxidative stress requires a multiparametric approach.
Integrating damage, antioxidant capacity, inflammation, and metabolism allows a biologically coherent reading of redox status.

✅ RELATED ARTICLE 6
Antioxidant Supplements: When They Are Truly Needed
Highlight
Antioxidant supplements are not a universal solution to oxidative stress.
In many cases, indiscriminate use is useless or potentially counterproductive.
The most effective strategy remains strengthening endogenous antioxidant defenses.

Why “more antioxidants = less ROS” is wrong
ROS:

are not only toxic byproducts
have essential physiological functions
Indiscriminately eliminating ROS can:

interfere with signaling
reduce beneficial adaptations
BOX — Key concept
The goal is not to suppress ROS, but to restore redox balance.

What dietary antioxidants really do
Dietary antioxidants:

partially buffer ROS
mainly activate signaling pathways (e.g., Nrf2)
Many polyphenols act more as adaptive signals than direct scavengers.

Evidence on high-dose supplements
Chronic high-dose vitamin C and E:

may reduce exercise metabolic benefits
may blunt Nrf2 activation
When supplementation may be useful
Documented deficiencies
vitamin C
vitamin E
selenium
zinc
Increased demand
high stress
infections
toxin exposure
recovery phases
Specific clinical conditions
malabsorption
selected chronic diseases
Types of integrative approach
Direct antioxidants

vitamin C
vitamin E
Glutathione precursors

N-acetylcysteine
glycine
Mitochondrial modulators

CoQ10
alpha-lipoic acid
BOX — Preferred strategy
Better to provide substrates and signals to produce endogenous antioxidants than large doses of external scavengers.

Risks of abuse
reduced training adaptations
possible increased mortality in some populations
false sense of security delaying lifestyle change
Correct intervention sequence
Sleep
Nutrition
Physical activity
Stress management
Only then: targeted supplementation
Supplementation and personalization
Good supplementation:

is temporary
is biomarker-based
is re-evaluated
Conclusion
Antioxidant supplements do not replace a healthy lifestyle.
They may play a targeted role in selected contexts, but the most effective protection against oxidative stress comes from strengthening the body’s intrinsic capacity.