Studi & Pubblicazioni

#IpofertilitàMaschile, #Omocisteina, #MTHFRSNP, #5MTHF, #OneCarbonCycle, #Folati

Clement 2023 – Integrazione di 5MTHF per l’iperomocisteinemia (HHcy)

“Hyperhomocysteinemia in hypofertile male patients can be alleviated by supplementation with 5MTHF associated with one carbon cycle support”

Autori: A. Clement, E. Amar, P. Clement, É. Sedbon, C. Brami, S. Alvarez e Y. Menezo

Capsula: L’omocisteina è nota per essere dannosa anche per l’infertilità maschile e un’alta percentuale di maschi infertili presenta un’elevata omocisteina. Un ampio gruppo di maschi infertili è stato sottoposto a un test dell’omocisteina prima e dopo l’integrazione con Impryl. Come si è visto nelle donne PCOS (vedi Schiuma 2020), anche negli uomini infertili Impryl ha ridotto l’omocisteina in tutti i pazienti trattati, compresi quelli che partivano da un valore normale. Molti dei pazienti hanno concepito dopo il trattamento. Vale la pena di prendere in considerazione l’analisi e il trattamento dell’omocisteina negli uomini che soffrono di infertilità.

Clement 2023 – 5MTHF supplementation for HHcy


Homocysteine (Hcy) is a cellular poison, side product of the
hydrolysis of S-Adenosyl Homocysteine, produced after the universal
methylation effector S -Adenosylmethionine liberates a methyl group to recipient targets. It inhibits the methylation processes and its rising is associated with multiple disease states and ultimately is both a cause and a consequence of oxidative stress, affecting male gametogenesis. We have determined hyper homocysteinhemia (HHcy) levels can be reliably reduced in hypofertile patients in order to decrease/avoid associated epigenetic problems and protect the health of future children, in consideration of the fact that treatment with high doses of folic acid is inappropriate.

Homocysteine levels were screened in male patients consulting for
long-standing infertility associated with at least three failed Assisted
Reproductive Technology (ART) attempts and/or repeat miscarriages. Seventyseven patients with Hcy levels > 15 μM were treated for three months with a combination of micronutrients including 5- MethylTetraHydroFolate (5-MTHF), the compound downstream to the MTHFR enzyme, to support the one carbon cycle; re-testing was performed at the end of a 3 months treatment period. Genetic status for Methylenetetrahydrofolate Reductase (MTHFR) Single nucleotide polymorphisms (SNPs) 677CT (c.6777C > T) and 1298AC (c.1298A > C) was determined.

Micronutrients/5-MTHF were highly efficient in decreasing circulating
Hcy, from averages 27.4 to 10.7 μM, with a mean observed decrease of 16.7 μM. The MTHFR SNP 677TT (homozygous form) and combined heterozygous 677CT/1298AC status represent 77.9% of the patients with elevated Hcy.

Estimation HHcy should not be overlooked in men suffering infertility
of long duration. MTHFR SNPs, especially 677TT, are a major cause of high homocysteinhemia (HHcy). In these hypofertile patients, treatment with micronutrients including 5-MTHF reduces Hcy and even allows spontaneous pregnancies post treatment. This type of therapy should be considered in order to ensure these patients’ quality of life and avoid future epigenetic problems in their descendants.

#Omocisteina, #PCOS, #FluidoFollicolare, #TassoBlastocistico, #Micronutrienti

Kucuk 2023 – Omocisteina follicolare nell’ovaio policistico (PCOS)

“Follicular homocysteine as a marker of oocyte quality in PCOS and the role of micronutrients”

Autori: T. Kucuk, P. E. Horozal, A. Karakulak, E. Timucin e M. Dattilo

Capsula: L’omocisteina è dannosa per la fertilità e alcuni studi hanno dimostrato che la quantità di omocisteina nei fluidi follicolari potrebbe essere direttamente coinvolta. È già stato dimostrato che Impryl riduce l’omocisteina nel sangue in tutte le donne trattate, quindi si è cercato di capire se Impryl riduce l’omocisteina anche nel liquido follicolare e se questo si associa alle gravidanze. Le donne PCOS sottoposte a un ciclo ART sono state analizzate per l’omocisteina follicolare dopo Impryl per 3 mesi o senza trattamento. L’omocisteina follicolare era direttamente correlata alle gravidanze e la sua diminuzione con Impryl ha segnato un miglioramento dell’esito clinico. È la prima volta che un’integrazione migliora i risultati clinici nei cicli ART.

Kucuk 2023 – Follicular HCY in PCOS


Does follicular homocysteine predict the reproductive potential of oocytes following FSH stimulation in PCOS women? Can it be modulated by dietary interventions?

This was a prospective, randomized, interventional clinical study. Forty-eight PCOS women undergoing in vitro fertilization at a private fertility clinic were randomized for a dietary supplementation providing micronutrients involved in homocysteine clearance or no treatment. The supplement was assumed 2 months before stimulation until pick-up day. Monofollicular fluids were collected and frozen. After embryo transfer, the fluids from the follicles generating the transferred embryos were thawed and analyzed.

Follicular homocysteine showed a negative correlation with clinical pregnancy both in the whole population (r =  − 0.298; p = 0.041) and in controls (r =  − 0.447, p = 0.053). The support achieved a non-significantly lower concentration of follicular homocysteine (median [IQR]–7.6 [13.2] vs 24.3 [22.9]). Supplemented patients required far less FSH for stimulation (1650 [325] vs 2250 [337], p = 0.00002) with no differences in the number of oocytes collected, MII rate, and fertilization rate. Supplemented patients enjoyed higher blastocyst rate (55% [20.5] vs 32% [16.5]; p = 0.0009) and a trend for improved implantation rate (64% vs 32%; p = 0.0606). Clinical pregnancy rates were 58% vs 33% in controls (p = ns).

Follicular homocysteine is a suitable reporter that might be investigated as a tool for oocyte-embryo selection. A diet enriched with methyl donors may be useful in PCOS and supplements may also help. These findings may be also true for non-PCOS women, which warrants investigation.

#Cisteina, #SulfideIdrogeno, #H2S, #LC-MS/MS, #L-Cistina, #Micronutrienti, #Piridossal 5-Fosfato

Dattilo 2022 – Modulazione del metabolismo H2S umano

“Modulation of Human Hydrogen Sulfide Metabolism by Micronutrients, Preliminary Data”

Autori: M. Dattilo, C. Fontanarosa, M. Spinelli, V. Bini and A. Amoresano

Capsula: Un integratore alimentare non è destinato a curare le malattie, tuttavia è giusto dimostrare quale sia l’effettivo effetto metabolico. Nel caso di Redostim, che introduce un’inversione di tendenza nella modulazione metabolica, ciò era ancora più importante. I volontari sono stati sottoposti a test prima e dopo l’assunzione di Redostim per valutare il loro metaboloma mediante analisi complesse di spettrometria di massa. I risultati confermano che Redostim induce H2S.

Dattilo 2022 – Modulation of human H2S metabolism


Hydrogen sulfide (H2S) is a pivotal gasotransmitter networking with nitric oxide (NO) and carbon monoxide (CO) to regulate basic homeostatic functions. It is released by the alternative pathways of transulfuration by the enzymes Cystathionine Beta Synthase (CBS) and Cystathionine Gamma Lyase (CSE), and by Cysteine AminoTransferase (CAT)/ 3-Mercaptopyruvate Sulfur Transferase (3MPST). A non-enzymatic, intravascular release is also in place. We retrospectively investigated the possibility to modulate the endogenous H2S release and signaling in humans by a dietary manipulation with supplemented micronutrients (L-cystine, Taurine and pyridoxal 5-phopsphate/P5P).

Patients referring for antiaging purposes underwent a 10-day supplementation. Blood was collected at baseline and after treatment and the metabolome was investigated by mass spectrometry to monitor the changes in the metabolites reporting on H2S metabolism and related pathways.

Data were available from 6 middle aged subjects (2 women). Micronutrients increased 3-mercaptopyruvate (P = .03), reporting on the activity of CAT that provides the substrate for H2S release within mitochondria by 3MPST, decreased lanthionine (P = .024), reporting the release of H2S from CBS, and had no significant effect of H2S release from CSE. This is compatible with a homeostatic balancing. We also recorded a strong increase of reporters of H2S-induced pathways including 5-MethylTHF (P = .001) and SAME (P = .022), reporting on methylation capacity, and of BH4 (P = .021) and BH2 (P = .028) reporting on nitric oxide metabolism. These activations may be explained by the concomitant induction of non-enzymatic release of H2S.

Although the current evidences are weak and will need to be confirmed, the effect of micronutrients was compatible with an increase of the H2S endogenous release and signaling within the control of homeostatic mechanisms, further endorsing the role of feeding in health and disease. These effects might result in a H2S boosting effect in case of defective activity of pathologic origin, which should be checked in duly designed clinical trials.

#Micronutrienti, #OneCarbonCycle, #Ovociti, #Blastocisti, #CheckpointOCM

Golestanfar 2022 – Tasso di blastocisti raddoppiato

“Metabolic enhancement of the one carbon metabolism (OCM) in bovine oocytes IVM increases the blastocyst rate: evidences for a OCM checkpoint”

Autori: A. Golestanfar, A. Niasari‑Naslaji, F. Jafarpour, S. Rouhollahi, N. Rezaei, Y. Menezo, M. Dattilo & M. H. Nasr‑Esfahani

Capsula: Articolo top su rivista top che indaga il ruolo del supporto OCM nella maturazione e nella competenza riproduttiva degli ovociti. Gli ovociti bovini immaturi sono stati coltivati e fatti maturare in vitro per 24 ore con o senza gli ingredienti di Impryl a una concentrazione simile alla somministrazione orale nell’uomo. Gli ovociti supportati hanno generato un numero doppio di embrioni maturi e l’effetto era interamente dovuto alla migliore metilazione del DNA materno (dal supporto). Questo dimostra che solo gli ovociti ben nutriti con micronutrienti sono in grado di generare un embrione. Per ottenere gli stessi risultati in ambito clinico, dovremmo trattare le future madri mentre maturano gli ovociti.

Golestanfar 2022 – Doubled Blastocyst Rate


The one carbon metabolism (OCM) has a primary role in the process of oocyte maturation. In this study bovine oocytes were cultured for 24 h, up to MII stage, with standard medium supplemented or not with 8 metabolic enhancers of the OCM and the MII and blastocyst rate were compared. Additional analyses were performed on matured oocytes, cumulus cells, zygotes and blastocysts. The OCM supplementation increased the blastocyst rate derived from in vitro fertilization. The mitochondrial mass and DNMT3a protein expression were increased whereas DNA fragmentation decreased in matured oocytes. DNA methylation in female pronucleus of zygotes was increased. The supplementation did not directly affect the redox balance as ROS and GSH in matured oocytes and homocysteine in the spent medium were unchanged. The supplementation of the oocytes with metabolic enhancers of the OCM may increase the yield from the culture, likely due to improved DNA methylation and epigenetic programming. The lack of effects on MII rate with huge differences appearing at the blastocyst stage suggest the existence of a OCM metabolic check point that hampers oocytes progression.

#SulfideIdrogeno, #H2S, #SARS-Cov-2, #Covid 19, #EmeOssigenasi1, #MonossidoDiCarbonio

Dattilo 2020 – Difese dell’ospite nella Covid 19

“The role of host defences in Covid 19 and treatments thereof”

Autore: M. Dattilo

Capsula: Questo è un articolo di revisione che spiega come il virus SARS-CoV2, responsabile della Covid 19, raggiunga la virulenza ostacolando il sistema H2S. Chi ha una bassa reattività costituzionale all’H2S è esposto a una grave malattia. I trattamenti che potenziano la segnalazione dell’H2S possono essere d’aiuto nella Covid 19. Questo è già possibile con i micronutrienti. Questo è già possibile grazie ai micronutrienti.

Dattilo 2022 – Modulation of human H2S metabolism


Hydrogen sulfide (H2S) is a natural defence against the infections from enveloped RNA viruses and is likely involved
also in Covid 19. It was already shown to inhibit growth and pathogenic mechanisms of a variety of enveloped
RNA viruses and it was now found that circulating H2S is higher in Covid 19 survivors compared to fatal cases. H2S
release is triggered by carbon monoxide (CO) from the catabolism of heme by inducible heme oxygenase (HO-1)
and heme proteins possess catalytic activity necessary for the H2S signalling by protein persulfidation. Subjects with
a long promoter for the HMOX1 gene, coding for HO-1, are predicted for lower efficiency of this mechanism. SARScov-
2 exerts ability to attack the heme of hemoglobin and other heme-proteins thus hampering both release and
signalling of H2S. Lack of H2S-induced persulfidation of the KATP channels of leucocytes causes adhesion and release
of the inflammatory cytokines, lung infiltration and systemic endothelial damage with hyper-coagulability. These
events largely explain the sex and age distribution, clinical manifestations and co-morbidities of Covid-19. The
understanding of this mechanism may be of guidance in re-evaluating the ongoing therapeutic strategies, with
special attention to the interaction with mechanical ventilation, paracetamol and chloroquine use, and in the
individuation of genetic traits causing increased susceptibility to the disruption of these physiologic processes and
to a critical Covid 19. Finally, an array of therapeutic interventions with the potential to clinically modulate the HO-
1/CO/H2S axis is already available or under development. These include CO donors and H2S donors and a boost to
the endogenous production of H2S is also possible.

#StudioClinico, #FertilitàMaschile, #Impryl, #Micronutrienti

Smits 2020 – Infertilità maschile idiopatica

“Impact of a nutritional supplement (Impryl) on male fertility: study protocol of a multicentre, randomised, double-blind, placebo-controlled clinical trial (SUppleMent Male fERtility, SUMMER trial)”

Autori: R. Smits, K. D’Hauwers, J. IntHout, D. Braat, K. Fleischer

Capsula: Questa è la presentazione ufficiale e la divulgazione dei dettagli di un vasto studio clinico con Impryl sull’infertilità maschile. Si tratta di uno studio clinico prospettico, randomizzato, controllato in doppio cieco rispetto al placebo in corso presso l’Università Radbaud, in Olanda. Lo studio, iniziato già nel 2018, prevede di includere 1200 pazienti da trattare per 6 mesi e seguire per 15 mesi. Originariamente la conclusione era prevista per dicembre 2023, ma ora si prevede che lo studio richiederà un altro anno per completare il follow-up dei pazienti trattati. Siamo molto orgogliosi di poter affermare che questo è lo studio più ampio e di migliore qualità mai condotto sull’infertilità maschile.

Smits 2020 – Idiopathic male infertility


Infertility is a worldwide problem and about 10%–15% of all couples will be affected by the inability to have children. In approximately 50% of infertile couples, a male factor is involved. Most of the male infertile cases are characterised as ‘idiopathic’, except for a small percentage of cases which are causative by a genetic aetiology. In the past decade, the role of oxidative stress related to sperm quality has been researched thoroughly and estimated to be the problem in 25%–87% of male infertility cases. Impryl is a nutritional supplement which works on the metabolic system and the regulation of oxidative stress by activating the 1-carbon cycle and therefore recycling of homocysteine. We hypothesise that the nutritional supplement Impryl in men of infertile couples might improve the ongoing pregnancy rate.

We designed a multicentre, randomised, double-blind, placebo-controlled clinical trial. We aimed to include 1200 male adults aged 18–50 years, part of a couple that is diagnosed with infertility. The couple will either start or has already been started with fertility treatment, that is, expectative management (duration of 6 months), intrauterine insemination (IUI) with or without mild ovarian stimulation or ovulation induction, either in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatment. Male participants will be randomised in either the Impryl or the placebo group, with identical appearance of the tablets to be distributed (doses: one tablet each day), for a total duration of maximal 6 months. Patients can start directly with fertility treatment and/or natural conception. The primary outcome is the number of ongoing pregnancies confirmed by ultrasound at ≥10 to 12 weeks, and conceived in the time window between randomisation up to and including month 6 of intervention use. Secondary outcomes are change in semen parameters between baseline and after 3 months of intervention in the IUI/IVF/ICSI group, based on (prewash) total motile sperm count. Furthermore the number of pregnancies conceived in the optimal intervention time window (after full spermatogenesis of 72 days), overall number of pregnancies, time to pregnancy, embryo fertilisation rate in IVF/ICSI, embryo-utilisation rate in IVF/ICSI, number of miscarriages, live birth rate and adverse events are documented within the study period of 15 months.

Ethics and dissemination:
The protocol is approved by the local medical ethical review committee at the Radboud University Medical Centre and by the national Central Committee on Research Involving Human Subjects. Findings will be shared with the academic and medical community, funding and patient organisations in order to contribute to optimisation of medical care and quality of life for patients with infertility.

Trial registration numbers:
NCT03337360 and NTR6551.

#Omocisteina, #Micronutrienti, #OneCarbonCycle, #PCOS 

Schiuma 2020 – Omocisteina nel sangue nell’ovaio policistico (PCOS)

“Micronutrients in support to the one carbon cycle for the modulation of blood fasting homocysteine in PCOS women”

Autori: N. Schiuma, A. Costantino, T. Bartolotti, M. Dattilo, V. Bini, M. C. Aglietti, M. Renga, A. Favilli, A. Falorni & S. Gerli

Capsula: Le donne affette da PCOS sono note per il rischio più elevato di aumento dell’omocisteina, che potrebbe essere correlato ai loro problemi di fertilità. Le giovani donne PCOS sono state randomizzate per l’integrazione con Impryl o per nessun trattamento e la loro omocisteina è stata controllata prima e dopo il trattamento. Impryl ha ridotto significativamente il livello medio di omocisteina nel sangue. Inoltre, tutte le pazienti trattate hanno ridotto l’omocisteina e la diminuzione media è stata significativa anche nel gruppo che partiva da valori normali.

Schiuma 2020 – Blood homocysteine in PCOS


Fasting blood homocysteine is increased in PCOS women and is involved in several of its co-morbidities including cardiovascular disease and infertility. Corrective interventions based on the administration of supra-physiologic doses of folic acid work to a low extent. We aimed to test an alternative approach.

This was a prospective, randomized, parallel group, open label, controlled versus no treatment clinical study. PCOS women aged > 18, free from systemic diseases and from pharmacological treatments were randomized with a 2:1 ratio for treatment with activated micronutrients in support to the carbon cycle (Impryl, Parthenogen, Switzerland—n = 22) or no treatment (n = 10) and followed-up for 3 months. Fasting blood homocysteine, AMH, testosterone, SHBGs, and the resulting FTI were tested before and at the end of the follow-up.

The mean baseline fasting blood homocysteine was above the normal limit of 12 μMol/L and inversely correlated with SHBG. AMH was also increased, whereas testosterone, SHBG, and FTI were within the normal limit. The treatment achieved a significant reduction of homocysteine, that did not change in the control group, independently of the starting value. The treatment also caused an increase of AMH and a decrease of SHBGs only in the subgroup with a normal homocysteine at baseline.

In PCOS ladies, blood homocysteine is increased and inversely correlated with the SHBGs. Physiologic amounts of activated micronutrients in support to the carbon cycle achieve a reduction virtually in all exposed patients. Whether this is of clinical benefit remains to be established.

#Metabolismo, #Micronutriento, #OneCarbonCycle, #Spermatozoi

Gallo 2018 – Gli stimolatori metabolici influenzano la funzionalità degli spermatozoi

“Metabolic enhancers supporting 1-carbon cycle affect sperm functionality: an in vitro comparative study”

Authors: A. Gallo, Y. Menezo, B. Dale, G. Coppola, M. Dattilo, E. Tosti & R. Boni

Capsula: Articolo di punta su una rivista di punta che indaga il ruolo del supporto OCM nella bioenergetica degli spermatozoi. I mitocondri producono ROS insieme ad ATP (energia) e possono continuare a rilasciare ATP finché sono in grado di neutralizzare i ROS generati. È stato dimostrato che i mitocondri degli spermatozoi umani godono di un’attività bioenergetica sostenuta nel tempo quando sono esposti ai micronutrienti di Impryl alla concentrazione raggiunta dopo la somministrazione orale.

Gallo 2018 – Metabolic enhancers affect sperm functionality


The sperm plasma membrane is a sensitive target to oxidative stress. The most representative reactive oxygen species (ROS) scavengers in the genital tract, hypotaurine and glutathione, require, for their synthesis, cysteine whose availability is associated with the 1-carbon cycle (1-CC). Human, bovine and ascidian spermatozoa were incubated with compounds supporting the 1-CC (Vitamin B6, Methylcobalamin, 5 Methyl Tetrahydrofolate, Zinc Bisglycinate and N-acetyl-cysteine) (TRT) and compared to the effects induced solely by N-acetyl-cysteine (NAC). In control groups (CNTRL), spermatozoa were incubated with medium alone. After 90 and 180 minutes of incubation, the mitochondrial membrane potential (ΔΨM) in TRT and NAC was significantly (P < 0.01) higher than in CNTRL. At H2DCFDA evaluation, ROS production differed between species whereas, at 2-OH Ethidium, it significantly decreased in bovine TRT group. Intracellular pH (pHi) did not significantly vary in relation to treatment. In ascidian spermatozoa, the NAC supplementation decreased external pH, which in turn brought to a pHi lowering. Buffering seawater with NaHCO3 reversed the beneficial effects of N-acetyl-cysteine supplementation. In conclusion, both fully supporting the 1-CC and treatment with N-acetyl-cysteine alone improved kinetics, ΔΨM and ROS production in mammalian sperm demonstrating for the first time the direct in vitro effects of these compounds on sperm functionality.

#FertilitàFemminile, #Micronutrienti, #OneCarbonCycle, #RiserveOvariche

Silvestris 2017 – Il One Carbon Cycle (OCM) ripristina la riserva ovarica nelle donne subfertili

“Supporting the One-Carbon Cycle restores ovarian reserve in subfertile women: absence of correlation with urinary Bisphenol A concentration”

Autori: E. Silvestris, M. Cohen, D. Cornet, L. Jacquesson-Fournols, P. Clement, J. Chouteau, M. Schneider, T. Besnard, e Y. Ménézo

Capsula: Cinquantacinque donne con un’anamnesi di infertilità di 3-7 anni e un basso livello di AMH sono state analizzate per l’AMH prima e dopo 4 mesi di supporto dietetico con micronutrienti a sostegno dell’OCM. Il loro valore di AMH è aumentato indipendentemente dal valore iniziale e dall’età, con una variazione media da 1,34 a 1,88 (p = 0,0001). Otto pazienti hanno concepito spontaneamente durante i 3 mesi di follow-up dello studio.

Silvestris 2017 – One-Carbon Cycle restores ovarian reserve in subfertile women


Environmental endocrine disrupting chemicals (EDCs), including bisphenol A (BPA), induce DNA methylation errors and oxidative stress, and alter fertility. Animal studies have demonstrated that supporting the one-carbon cycle (1-CC) with appropriate dietary supplements can reduce the effects of EDCs. Anti-Mullerian hormone (AMH), a marker of ovarian functionality, has been tested in subfertile female patients, to control this hypothesis in humans. Fifty-five women with a history of 3–7 years of infertility, with at least two assisted reproductive technology (ART) treatment failures, and low serum levels of AMH were enrolled in the study. Before starting any further ART treatment, they were tested for AMH and for follicular count. A urinary control of BPA was proposed. Then a support of the 1-CC, already tested in other clinical studies, was initiated and continued for 4 months. At the end of this period, antral follicle count and serum AMH levels were re-evaluated. The AMH levels before and after treatment were compared using the Wilcoxon test (nonparametric test, non-Gaussian population). Out of the 55 patients, 35 accepted a BPA dosage in the urine. No correlation was found between BPA and serum AMH concentrations. Forty-nine patients followed the full treatment with 1-CC supplements, which resulted in increased AMH levels, independent of initial AMH levels and maternal age (in the range studied), p = 0.0001. Eight patients spontaneously conceived ongoing pregnancies within 3 months, at the end of the protocol. A support of the 1-CC can partly alleviate metabolic derangements induced by environment, as observed in animal models, and improve endocrine background in women.

#Gameti, #Ovociti, #StressOssidativo, #DNA, #Metilazioni, #Epigenetica

Dattilo 2016 – Nutrire il sistema di antiossidanti migliora la qualità dei gameti

“Improvement of gamete quality by stimulating and feeding the endogenous antioxidant system: mechanisms, clinical results, insights on gene-environment interactions and the role of diet”

Autori: M. Dattilo & G. D’Amato & E. Caroppo & Y. Ménézo

Capsula: Il ruolo dell’OCM nell’infertilità maschile viene esaminato insieme agli effetti positivi di un’integrazione con donatori di metile. Questi effetti sembrano direttamente correlati al miglioramento delle metilazioni che porta a una migliore maturazione degli spermatozoi e a una riduzione dei danni al DNA. Viene spiegato il razionale dell’Impryl, la copertura dell’intero percorso e l’uso di micronutrienti pre-attivati.

Dattilo 2016 – Feeding the antioxidants system improves gamete quality


Oxidative damage triggers extensive repair in gametes and thereafter in the zygote but it results in clinically
relevant damage when affecting the maturation of the gametes
chromatin, i.e. padlocking and epigenetic marking. It associates with defective DNA methylation and/or with oxidation of
the methyl marks leading to derangement of gamete epigenetics, defects of chromatin condensation and aneuploidy. A
proper feed to the one carbon cycle has the potential to stimulate the endogenous antioxidant defences, i.e. gluthatione
synthesis, and to activate compensative homeostatic mechanisms restoring both the oxy-redox balance and DNA methylation, which are indeed strictly cross-regulated. This has
been shown to produce measurable clinical improvements of
male reproductive potential in pilot studies herein
summarised. However, the effects of dietary habits and of
supplementations are variable according to the individual genetic substrate, as genetic variants of several of the concerned
enzymes occur with high frequency. Individual risk assessments and personalised interventions are still difficult to implement, in the meantime, a very varied diet may facilitate
metabolic compensation in the majority of the cases. This
review aims to report on the mechanisms of damage, on the
opportunities to modulate the physiologic oxy-redox
homeostasis by means of a varied diet or dietary supplements
and on the open issues related to the genetic variability of the

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