Endometriosis: how it manifests itself

Endometriosis is a gynecological disease characterized by the growth of endometrial tissue outside its physiological localization, such as the myometrium, ovary and peritoneum resulting in inflammation, fibrosis, adhesion formation and bleeding during menstruation.

This condition is often associated with pelvic pain and subfertility and severely affects the quality of life of women of reproductive age. Affected women often require surgery when drug therapy fails. Its prevalence is about 10% and up to 7 out of 1000 women are affected each year as well as another significant percentage of undiagnosed cases and even some studies suggest that every woman may have endometriosis as a transient fertile age phenomenon.

The exact pathogenetic mechanism is still not completely clear, but the accepted hypotheses are:

• retrograde menstruation
• genetic or immunological susceptibility
• the remains of the Mullerian ducts, embryonic structures from which the fallopian tubes, uterus and cervix develop and which would not completely differentiate during fetal development
• exposure to endocrine disruptors, i.e. substances that alter the functionality of the endocrine system.

Early menarche, late menopause and obesity can contribute to prolonged exposure to endogenous estrogens which contributes to the onset of the disease.

Endometriosis is associated with an increased risk of developing autoimmune diseases and various forms of carcinoma, not only involving the reproductive system.

Chronic inflammation and endometriosis

The hormonal imbalance in endometriosis mainly causes the alterations of multiple cellular functions and is the basis of a state of chronic inflammation that perpetuates and amplifies the problems of this pathology throughout the woman’s reproductive life. The chronic inflammatory state is also at the basis of the alteration of the pain signal, and progressively increases its sensitivity.

In endometriosis, several inflammatory mediators are produced: prostaglandins, vascular endothelial growth factor, tumor necrosis factor alpha, nerve growth factor, and various interleukins. In particular, cytokines act as messengers for the immune system and control a variety of biological processes, including inflammation and repair, innate and acquired immunity, and angiogenesis.

Oxidative stress and endometriosis

The inflammatory response could be the result of oxidative stress, that is, an imbalance between reactive oxygen species (ROS) and the body’s antioxidant capacity, which could be implicated in the pathophysiology of endometriosis causing a general inflammatory response in the peritoneal cavity.

Reactive oxygen species are intermediates produced by normal oxygen metabolism and are inflammatory mediators known to modulate a range of cellular activities and to have deleterious effects on the cell and organism if the physiological balance with antioxidant defense systems was compromised. Macrophages, erythrocytes and apoptotic endometrial tissue that graft into the peritoneal cavity through retrograde menstruation are well known inducers of oxidative stress by releasing pro-oxidative and pro-inflammatory factors, involved in the formation of ROS.

A close relationship between oxidative stress and endometriosis is well documented in the literature. Numerous preclinical studies have shown that some antioxidants could effectively decrease the state of oxidative stress and reduce endometriotic lesions.

Pay attention to nutrition in case of endometriosis

[/vc_column_text][vc_column_text css=”.vc_custom_1619606106731{padding-top: 10px !important;padding-bottom: 10px !important;}”]Lifestyle is fundamental in the onset and course of this disease, the diet in particular is able to control the inflammatory state and enhance the body’s antioxidant capacity, supporting the physiological defense enzymatic systems.

FATTY ACIDS

Alpha-linolenic acid (omega-3) and gamma-linolenic acid (omega-6) are able to reduce inflammation by affecting the type of eicosanoids produced, particularly prostaglandins and leukotrienes. Foods rich in these two fatty acids are:

– oils derived from flaxseed, walnuts and pumpkin (alpha-linolenic acid);

– borage, black currant and evening primrose oils (gamma-linolenic acid).

Several scientific studies have reported an inverse association between the risk of endometriosis and the intake of omega-3 polyunsaturated fatty acids. Furthermore, the inadequate intake of these fats by women with endometriosis promotes inflammation and consequently oxidative stress.

On the contrary, omega-3 fatty acids, competing with pro-inflammatory omega-6 fatty acids, for the same enzymes and removing them from the chain of events that induce the production of inflammatory mediators, improve symptoms and the inflammatory state. In addition, the omega-3 EPA and DHA are the precursors of molecules called “resolvins” which have been shown to apply a resolving effect of inflammation in animal models. Studies are still ongoing, but promising if we consider that inflammation may be one of the therapeutic targets of this disease.

Instead, animal fats derived from red meat and milk derivatives, rich in arachidonic acid and trans fats, cause an increase in inflammation and a greater activity of spasms in endometriosis due to the prostaglandins produced.

ANTIOXIDANTS

Antioxidants and a combination of vitamins and minerals have a positive effect on the symptoms of endometriosis.

Research has suggested that there is a direct association between a low dietary intake of vitamin-bearing vegetables involved in supporting antioxidant systems such as A, C, E, immune systems such as D, and a high intake of trans fatty acids, rom red meats and alcohol.

Antioxidants, such as vitamin C capable of preventing lipid peroxidation, vitamin E and beta-carotene have been shown to have positive effects on endometriosis. Vitamin C and vitamin A analogues have been shown to have an inhibiting effect on the growth and size of endometrial cysts. Furthermore, the antioxidant vitamins E and C could be involved in the elimination of free radicals and ROS which are responsible for the growth and adhesion of endometrial cells. Furthermore, supplementation with vitamin C, E and n-acetyl cysteine ​​appears to be able to reduce pain related to oxidative stress in endometriosis. Also fundamental is coenzyme Q10, present in fish such as salmon, sardines, anchovies, mackerel and a powerful antioxidant that works in synergy with vitamins stabilizing our cell membranes. Coenzyme Q10 is also produced by the body, but its production constantly decreases with age or due to chronic diseases and supplementation may be advisable in the case of endometriosis.

FOODS FOR LIVER SUPPORT

A predominantly vegetarian Mediterranean diet is useful for reducing the symptoms of endometriosis. Vegetables, in fact, represent an essential source of vitamins, coenzymes and antioxidants that intervene to support the detoxifying enzymatic systems of the liver.

Improving the detoxification mechanisms is important to cleanse estrogen, decrease the load of free radicals and eliminate xenoestrogens.

• Crucifers such as broccoli, cauliflower, cabbage, Brussels sprouts are vegetables with a high content of indole-3-carbinol which contributes to the metabolization of estrogen in the liver;
• Quercetin, an antioxidant present in apples, cherries, in some bulbs such as garlic and onion, in orange-colored fruits and vegetables, such as some citrus fruits, acts as a powerful antioxidant, has anti-inflammatory properties and would be able to inhibit neoplastic growth;
• Curcumin especially combined with black pepper piperine is widely recognized for its anti-inflammatory benefits and antioxidant activity. On animal models it would allow to prevent and reverse endometrial lesions;
• A high sugar intake, on the other hand, would be associated, like the intake of caffeine, with the development and severity of endometriosis symptoms.

The adequate intake of all these nutrients through food and appropriate supplementation is therefore essential for the support and modulation of endometriosis symptoms and to give quality to the life of women who suffer from it.

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Bibliographical references:

www.ncbi.nlm.nih.gov/pmc/articles/PMC7826862/
www.ncbi.nlm.nih.gov/pmc/articles/PMC5625949/
www.researchgate.net/publication/247770015
https://pubmed.ncbi.nlm.nih.gov/33435569/
https://pubmed.ncbi.nlm.nih.gov/33321760/
www.scienceinquest.com/open-access/fulltext/jnds/nutritional-protocol-for-endometriosis.php

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To have more information:

• Antioxidant supplementation: https://www.lipinutragen.it/en/antioxidant-integration/

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Article edited by

Dr.ssa Nicoletta Bocchino – Nutritionist Biologist

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Photo: 123RF Archivio Fotografico: 128228984 : ©rastudio / 123rf.com ; 38622451 : ©Sergei Vinogradov / 123rf.com

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FROM SOFT-GEL CAPSULES TO MICROEMULSIONS

The research in the pharmaceutical field has addressed a crucial aspect of the efficacy of drugs and biologically active substances: the effective ability of administration (oral versus intramuscular and intravenous) to make the active ingredients bio-available rather disposal to enter into the bloodstream to reach the cellular/biological target on which the intervention it’s desired, to improve the subject’s state of health.

The so-called “soft-gel” capsules (“soft” capsules, as they were defined in an advertisement) are an example of administration (or pharmaceutical form), orally that has brilliantly resolved the loss of active substances in the stomach, as is the case for non-gastro-resistant tablets or capsules. The soft gel capsules are made of layers of gelatin (animal or vegetable) that contain the pharmaceutical or nutraceutical preparation, and the outer layers “flake” as they pass between the stomach and duodenum, releasing the active substances in the gastrointestinal tract where they can already be emulsified (as happens for the nutrients), to then be absorbed by the intestinal cells and start their path in the circulation reaching the target.

It should be emphasized that by improving bioavailability with soft-gel capsules, it was possible to use lower dosages of active substances, because the formulation becomes more “protected”, even with “delicate” active ingredients, and their presence in the circulation is more constant. Therefore, improvements in side effects were also found. Furthermore, in the soft gel capsule formulations have been created with substances of a very different nature, namely substances that dissolve in water together with substances insoluble in water, because they can “coexist” in the soft-gel capsule that acts as a container.

In this perspective of improving bioavailability, oral administration of liquids has returned, again for two reasons: 1) to protect better the active substances directly exposed to the action of gastric acidity, as in the case of vitamins, amino acids and peptides, o easily degradable/oxidizable molecules; 2) make hydrophilic and lipophilic substances coexist in the same formulation and allow their absorption.

EMULSION: WHAT IS IT ABOUT?

Inspired by what happens in nature, the emulsion is the typical liquid form in which substances of different nature coexist, and in it typical “drops” of different size are formed which contain the active ingredients and which are in suspension because each drop is wrapped in a layer of molecules (emulsifiers) that can “coexist” in both aqueous and non-aqueous environments (thus creating the water/oil suspension). One of the best known natural emulsions is milk. One of the emulsions we prepare in the kitchen is mayonnaise.

In the pharmaceutical or nutraceutical preparation, more detail has been given to the size of these drops or, thanks to the choice of ingredients called “emulsifiers”, microemulsions, nanoemulsions and macroemulsions can be obtained based on the size of the suspended particles.

Img. 1: Types of emulsions distinguished by particle size (Callender et all. Int J Pharm. 2017)

Since 2011, the pharmaceutical industry and scientific research, given the glimpsed applicability of the use of this particular type of formulation, have worked hard on the subject, publishing more than 430 scientific releases in 5 years.

WHAT ARE THE MICROEMULSIONS?

Img. 2: Schematic representation of an oil particle in water (Callender et all. Int J Pharm. 2017)[/caption]

Microemulsions, as the term already defines, indicate the mixture of two or more liquid ingredients that are immiscible with each other, that with the use of emulsifying agents and mixing by machinery, similar to a kitchen mixer, are able to form the drops that remain in suspension and therefore take on a homogeneous appearance, and providing a liquid appearance, sometimes even transparent.

The oil-water mixture (O/W) in microemulsions is obtained when the particles take on very small dimensions (from 10 to 100nm), because specific emulsifiers and stabilizers have been used, and they find that organization that brings them into equilibrium with the watery world that surrounds them.

Always observing nature, emulsified particles are always used to absorb substances (as happens in nutrition when chylomicrons are formed in the gastrointestinal tract). Furthermore, microvesicles are those that transport biological molecules such as vitamins, peptides, transmitters, hormones through the bloodstream and protect these delicate substances from degradation that would occur by the action of enzymes dissolved in the plasma or by the action of oxidants.

WHY CHOOSE A MICROEMULSION:

As studied in the pharmaceutical field, microemulsions improve the biodistribution of active ingredients, be they drugs or supplements. Let’s see the reasons for this improvement:

• as noted above for the soft-gel capsules, they improve the transition phases in the gastro-intestinal system and the protection from degradation, because the outer part of the vesicle resists the acidic environment, quickly passing into the gastro-intestinal tract of absorption;
• for microemulsions there is an additional advantage, which is expressed precisely at the moment of absorption, both intestinal and above all later in the passage into the cells of the target tissue. This is because the outer part of the vesicle closely resembles the lipid composition of cell membranes. In fact, cell membranes are made up of phospholipids that surround the cell allowing life to take place in an environment mainly made up of water, inside and outside the cell. The microvesicle that comes into contact with the cell membrane has a perfect compatibility of the molecular structure, so there is a progressive penetration into the phospholipid layer, up to bringing the whole vesicle inside the cell and obtaining both the penetration into the bloodstream and the subsequent release of the active substances when the vesicle will endup into the cellular target.

An advantage of microemulsions, above all forms of administration, is the swallowing facility of the liquid form, so a long and interesting evolution of this type of choice is expected when treating people who are not able to swallow (all the pediatric sector) or fragile.

In the microemulsion form we also see an easier “personalization” of the treatment, both because they can be dosed and because different formulations can be mixed together, thus allowing to obtain a “liquid and bioavailable strategy” of high precision.

This is ideal for the NUTRILIPIDOMIC strategy or the choice of the right type and dose for each molecular profile, that is the goal to which the 4 P MEDICINE (Preventive, Predictive, Personalized and Participatory) should aim.

INTEGRATION OF OMEGA-3 DHA

Polyunsaturated fatty acids are essential for the body, as explained several times in various articles of the LipiMagazine Blog (see further details).

In the research conducted by the Lipidomics Laboratory Lipinutragen regarding the lipidomic profiles of frail people (aging, pediatric deficits), the importance of docosahexaenoic acid DHA supplementation was highlighted, fatty acid of the omega-3 family, an important structural component of membranes and molecular element/precursor fundamental for countless cellular functions.

The moments in which it may be needed the intake of DHA are identifiable in the growth and development of the child or in neurological problems and broad-spectrum aging. Conditions affecting people who may be reluctant to take capsule preparations.

The topic of integrations in microemulsions under these conditions has become a nutraceutical project approved by the Evaluation Group of the Innovation Accelerators structure at the National Research Council, Research Area of ​​Bologna, and has led to the birth of our R&D laboratory at the Accelerators. A research project was developed in collaboration with the University of Bologna as part of an Industrial Doctorate supported by Lipinutragen, and the results were used by the Lipinutragen R&D Division to develop the first preparation of omega-3 DHA in microemulsion to be made available on the nutraceutical market.

Li DHA, THE FIRST MICROEMULSION DHA

Li DHA is the first food supplement based on DHA in the form of a microemulsion, which is a product in liquid form that ensures quality and metabolic efficiency of the active ingredients. Li DHA has been specially designed to facilitate the absorption of DHA at the level of cell membranes, the site where the functions of DHA for the body are carried out.

The DHA raw material, carefully selected and contained in Li DHA, comes from a source of marine origin certified for the absence of contaminants and heavy metals. It is present in the form of triglycerides containing more than 97% of Omega-3 deriving from fish oil with a DHA concentration greater than 85% and with very low percentages of saturated fatty acids and almost no trans-fat.

Li DHA, being in liquid form, is easy to assume, ready to drink or to mix in a meal for an immediate combination with food.

Suitable for children from 6 months and for people with swallowing difficulties.

Li DHA is presented in packs of 10 vials of 10 mL equivalent to 20 doses. There is a line on the vial indicating the recommended daily dose (5 mL = 1 teaspoon, containing 250 mg of DHA, recommended daily dose).

For further information visit the website www.lidha.it.

Li DHA is a supplement, therefore it should not be intended as a substitute for a healthy and balanced diet. The information provided must in no way replace the direct relationship between health professional and patient. It is therefore advisable to consult your doctor and/or pharmacist.

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Bigliography:

1 – Callender SP, Mathews JA, Kobernyk K, Wettig SD. Microemulsion utility in pharmaceuticals: Implications for multi-drug delivery. Int J Pharm. 2017 Jun 30;526(1-2):425-442. doi: 10.1016/j.ijpharm.2017.05.005. Epub 2017 May 7. PMID: 28495500.
2 – Froelich A, Osmałek T, Jadach B, Puri V, Michniak-Kohn B. Microemulsion-Based Media in Nose-to-Brain Drug Delivery. Pharmaceutics. 2021 Feb 2;13(2):201. doi: 10.3390/pharmaceutics13020201. PMID: 33540856; PMCID: PMC7912993.
3 – Hoar T, Schulman J. Transparent Water-in-Oil Dispersions: the Oleopathic Hydro-Micelle. Nature. 1943 Jul 24; 152, 102–103. doi: org/10.1038/152102a0

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Further information on our LipiMagazine BLOG:

• Evidence of neuro disorders: https://www.lipinutragen.it/en/autism-essential-fats-lipidomic-membrane-analysis/
• Role of omega-3s in postpartum depression: https://www.lipinutragen.it/en/postpartum-depression/
• DHA supplementation in pregnancy: https://www.lipinutragen.it/en/the-role-of-dha-in-pregnancy/

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Article by the Editorial Group of Lipinutragen

The information provided must in no way replace the direct relationship between health professional and patient.

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Photo: 123RF Archivio Fotografico: 118161172 : ©Pavlo Syvak / 123rf.com

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How to satisfy fetal needs

DHA is a polyunsaturated fatty acid (PUFA) belonging to the omega-3 series. Its biological activity is carried out in the membranes of all the cells of the organism where it is present in variable proportions depending on the cell type, reaching about 7% in the neuronal membranes and 20% in the retina.

Although our cells have the enzymes for the synthesis of DHA, the production by our body is highly inefficient and therefore DHA is considered a semi-essential fatty acid that must be intake with food. The main source of DHA is fish as it feeds on algae and, for this reason, acts as an accumulator of lipids that the algae themselves biosynthesize.

FATTY ACIDS REQUIRED for and by the FETUS

All fatty acids are necessary for the development and growth of the fetus, both as a source of energy and as constituents of the membranes, without which the new cells in the process of formation would not exist. During pregnancy, the woman must provide both her own needs for fatty acids and that of the fetus and placenta.

The requirement changes according to the stage of gestation, reaching the highest levels in the last trimester, when the demand for growth and formation of the organs of the fetus is highest. Polyunsaturated fatty acids, omega-3 and omega-6, in addition to their structural role, as necessary components of cell membranes, play a crucial metabolic role as signalers and precursors of effector molecules.

The availableness during pregnancy of PUFA fatty acids for all these biological processes depends on the set of:

• levels assumed before conception (maternal reserves);
• levels taken during pregnancy (direct intake from the diet).

It is referred to factors that the (future) pregnant woman can control with an adequate nutritional approach. To these must be added the normal biological mechanisms that regulate:

• the correct functionality and selectivity of the placenta in the passage from mother to fetus;
• the placental and fetal synthesis of long-chain PUFA.

DHA during the trimesters of pregnancy

Although the mother’s energy needs increase as the pregnancy progresses, this does not mean that the expectant mother has to “eat for two”. In fact, it is certainly more important to guarantee the adequate type of fat taken, precisely because of their structural and functional role in the formation of the new organism.

It has been estimated that the total amount of DHA in the fetus up to birth is 10 g, of which 60-70% is mainly accumulated during the last 10 weeks of pregnancy.

To this quantity, which must be made bioavailable during 9 months, with a peak in the last quarter, must be added the daily requirement of the mother, which, to date, is estimated to be satisfied with a daily intake of 250 mg of DHA (for an adult individual according to EFSA recommendations).

How can the mother ensure adequate levels of DHA for herself and to accompany the growth of the fetus?

Pre-conception DHA reserves and dietary intake

The fetal need for DHA is satisfied both by the nutritional contribution and by the mobilization of pre-existing maternal reserves from the adipose tissue.

On the other hand, the contribution of the maternal, placental or fetal synthesis of DHA, starting from its precursor, alpha-linolenic acid (18: 3, omega-3), is not considered relevant.

• pre-conception diet: formation of maternal reserves

The woman’s usual diet before conception determines the composition of the maternal reserves that will be mobilized mainly during the last trimester of gestation.

It has been shown that the lipid structure of women immediately before conception (maturation of the ovum) and in the very early stages of pregnancy (implantation of the embryo) has a greater effect on the fetus than the nutritional intake in the last two trimesters of pregnancy. One of the explanations lies in the correct formation of the placental barrier which will determine the effective entity and selectivity of the mother-fetus exchanges, a factor that cannot be directly controlled and influenced during pregnancy.

Last but not least, adequate maternal reserves at the time of increased fetal DHA demand represent an evolutionary advantage since they allow a constant supply to the fetus, regardless of dietary fluctuations.

 

• diet in pregnancy: DHA directly from the nutrition of the pregnant woman

The DHA taken with the diet by the pregnant woman must be sufficient so that the pre-existing reserves are not depleted, compromising both the psycho-physical health of the woman that the lactation phase and/or subsequent pregnancies.

Of the “quantity” of DHA taken during pregnancy with the diet, it must be taken into consideration that a percentage will not reach the fetus (nor the cell membranes of the mother) in the event that tissue inflammation or conditions of cellular oxidative stress exist. Furthermore, it has been shown that a diet rich in omega-6 determines a decrease in the levels of omega-3 measurable in the umbilical cord at birth, indicating the establishment of a competition phenomenon between PUFA lipid elements transferred to the fetus.

Supplements in pregnancy

During pregnancy, depending on the stage of gestation, the mother will fulfil the fetus’s DHA needs by drawing from its reserves (fat deposits and cell membranes) and with the daily intake from the usual diet.

Numerous studies have shown the correlation between levels of circulating maternal DHA with those encountered in the umbilical cord at birth and with a longer duration of gestation, greater length and weight at birth and reduced risk of pre-term birth.

A balanced diet regarding omega-3 fatty acids provides that the daily requirement of DHA for an adult is 250 mg per day [1] which can be satisfied taking into account that in 100 grams of fish there can be up to 500 mg of omega-3 (EPA and DHA) (link parole sottolineate con https://www.lipinutragen.it/en/fish-omega3-rich-food/).

If the intake is adequate from before conception, the transfer of DHA to the fetus, whether it comes from pre-existing stores or directly from the diet, will be sufficient and will not deplete the maternal reserves. In fact, it has been seen that, since placental and fetal synthesis is negligible, the DHA reaching the fetus depends exclusively on the circulating maternal concentrations.

If, after a careful evaluation of the levels of DHA in the cell membranes of the mature erythrocyte, integration is considered necessary, it should not be forgotten that:

1. Excessive levels of omega-3, due for example to non-personalized supplementation, can decrease the levels of omega-6, which are also necessary for the fetus and for the good course of pregnancy. Furthermore, they can predispose cells to oxidative stress and the formation of toxic lipid species;
2. omega-3 supplements not adequately protected by a suitable antioxidant formulation, are “lost” before reaching their biological destinations, thus resulting in an ineffective supplement;
3. low quality omega-3 supplements, may contain high concentrations of elements, such as trans fatty acids and environmental contaminants (PCBs, dioxins, heavy metals).

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References:

[1] EFSA Journal 2010 8(3): 1461
[2] Wynn M, Wynn A. The case for preconception care of men and women. Bichester, United Kingdom: AB Academic, 1991:64–84
[3] Al MDM, van Houwelingen AC, Badart-Smook A, Hornstra G. Some aspects of neonatal essential fatty acid status are altered by linoleic acid supplementation of women during pregnancy. J Nutr 1995;125:2822–30.

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Further information on our LipiMagazine BLOG:

Polyunsaturated fatty acids: “The essentiality of polyunsaturated fatty acids“

DHA: “omega-3 DHA: “when fats become our best allies for health“

Integration of DHA: “Omega-3 DHA essence”

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Article by the Editorial Group of Lipinutragen

The information provided must in no way replace the direct relationship between health professional and patient.

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Photo: 123RF Archivio Fotografico: 92907479 : ©Sergii Gnatiuk / 123rf.com | 94372917: @Antonio Guillem / 123rf.com

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Toward conscious supplementation

The “Choice of Supplement” section continues with the article on ANTIOXIDANTS. Currently on the market exist a multitude of food supplements with antioxidant activity and the choice result to be difficult to take. It isn’t easy at all to identify what needed.

What characteristics should have a supplement with antioxidant activity? Who’s the target? How to choose them? Let’s start from the physiological aspect to understand how antioxidants act, what is the mechanism, or rather what are the various mechanisms of action, to try to answer these questions.

FREE RADICALS and PRODUCTION in CELLS: are they PHYSIOLOGICAL?

The cells, which form the tissues and are fundamental units of the body, are subject to various events that lead to the formation of free radicals. In particular, among Reactive Oxygen Species (ROS), which are products of chemical reactions catalyzed by light or enzymatic under the same physiological conditions that use oxygen, radical species are generated in which oxygen is found with only one electron and becomes very responsive. The radical tries to return to the stable condition, that of a molecule, by subtracting the missing electron or hydrogen atom, but acting so it forms other radical species and triggers a chain reaction, which stops only when the radical meets the natural donor of electrons or hydrogen which is an antioxidant enzyme. There are also other molecules capable of “stopping” the oxygen-centered radical, namely VITAMINS or ANTIOXIDANT COMPOUNDS that are taken from the diet (olive oil, vegetables, fruit). Taking into account that these compounds are not produced by the body independently, the set of ENZYMES and MOLECULES constitutes the so-called ANTIOXIDANT NETWORK.

If the formation of radical species is kept in balance with the antioxidant network, everything remains within “physiological” values, otherwise the “radical stress” is not stopped in time and cell damage becomes excessive, causing the destruction of molecules crucial for life (DNA, proteins, lipids) with damage to the functioning of the whole cell.

Knowing of the existence of this balance, the production of free radicals should not be seen as a negative event, as it tends to do, because it represents an important and necessary physiological mechanism for the activity of the organism; ROS species are those produced by cells of the immune system (Macrophages) to destroy pathogenic elements such as bacteria and viruses, and we can only imagine what would happen if they were not there. Furthermore, as studied in the last 30 years, without free radicals DNA and prostaglandins would not be formed, that is, there would be no hereditary transmission or inflammatory and anti-inflammatory cellular reaction.

Finally, the physiological mechanism that leads from oxygen and electrons to cellular energy in the mitochondria (organelles defined as the “lungs” of the cell) would not happen, and even our movements, or sports activities, could not be realized.

On the other hand, conditions such as intense sport, psychophysical stress, infections, environmental pollution, smoking, in combination with unregulated lifestyles and low dietary intake of antioxidants, can lead the cell to increase the production of free radicals and not have the same increase in defenses.

ANTIOXIDANTS AGAINST FREE RADICALS

As we have said, enzymatic and molecular antioxidant systems are necessary for the control of free radicals.

The task of “defusing” free radicals is entrusted to:

• Endogenous systems, i.e. produced and regenerated by the organism itself, such as systems based on enzymes: Superoxide dismutase, Catalase, Peroxidase, some proteins (Albumin), small molecules (Cysteine, Glutathione, Bilirubin, Uric acid, Coenzyme Q10), which they interact with radicals as explained above;
• Exogenous systems, i.e. coming only from external sources, which are molecules taken with food (mainly found in fruit, vegetables, cereals and legumes, olive oil, olives, green tea), which support endogenous detoxifying mechanisms. These are mostly Vitamins A, C and E, Minerals in particular Selenium, Zinc and Copper and other molecules Polyphenols, Flavonoids, Lycopene, Carotenoids.

It is important to say that BOTH systems are important, because they enter into SYNERGY of activity and regeneration, after the reaction with the radicals, in order to always keep the quantity and quality of their components constant.

OXIDATIVE STRESS, WHICH CONSEQUENCES

The antioxidant network with the endogenous and exogenous systems are the DEFENSE against free radicals, and if the result is balance, it means that the production of free radicals, even under stress, has been able to respond adequately.

If, on the other hand, oxidative stress prevails, the consequence is to accumulate degradation products that accelerate cellular aging, also leading to evident signs of sagging for the skin, weakening for the immune system and, if the damage causes mutations in the genetic equipment, also to open the way to the tumor.

SUPPLEMENTS with ANTIOXIDANT ACTIVITIES

How many times, due to incorrect eating habits, an inappropriate lifestyle and environment (smoking, stress, exposure to pollutants), we risk weakening the “ammunition” available to the body to balance radical stress. Low intake of fruit and vegetables and olive oil, but also demand for high physical performance and intense sport, exposure to the sun or sources of radiation, some diseases with a strong oxidative component, such as metabolic and cardiovascular diseases, are just some of the conditions in which the antioxidant defenses are depleted and oxidative stress may not find compensation.

In all these cases, the supply of antioxidants, both through nutrition and as a supplement, is strongly recommended in order to provide the body with what it needs, taking care to always provide balanced doses and synergistic molecules in their function.

Professionally chosen antioxidants, recommended only after an in-depth evaluation, will allow, in addition to maintaining a complete and efficient “network”, also to give us the “signs” of the success of the strategy, with:

– strengthening of the immune system to keep it active and reactive;

– prevention of skin aging and wrinkle formation, a consequence of the deterioration of important skin lipids and collagen and elastin fibers related to free radicals;

– improvement of physical and mental efficiency, especially when there are evident drops in performance due to the prolongation of exposure to stress.

– Improvement of physiological control in sport, with repercussions on performance and recovery times.[/vc_column_text][vc_column_text css=”.vc_custom_1615809016939{padding-bottom: 10px !important;}”]

ANTIOX advance, the ANTIOXIDANT REFILL

ANTIOX advance comes from an in-depth knowledge of the molecular mechanisms of oxidative stress and of the molecules essential for its control. The formulation of an antioxidant cannot fail to take into account the CELL MEMBRANE, which is the first site of interception of stress finding itself enveloping every cell in our body. Therefore, the advanced antioxidant formulation is recognized for being composed of molecules that can interact with free radicals in both aqueous and “lipophilic” (fatty) parts such as those that compose the membrane.

The two sectors WATERY AND LIPOPHILIC coexist in our cell and, since stress is generated in both, the natural network acts by reaching them both. Therefore, let’s make sure that in the formulation of the antioxidant there are BOTH TYPES OF MOLECULES, to have complete control.

This way, the formulation is indicated in cases of increased need for substances with antioxidant action to act synergistically in the control of free radicals and oxidative stress and in maintaining the functionality of the cell membrane.

ANTIOX advance contains a calibrated pool of synergistic antioxidant molecules for all-round cell protection. Detailed:

• antioxidant triad consisting of vitamins C (hydrophilic) and E and astaxanthin (lipophilic) for excellent protection against peroxidation of cell membrane lipids and intercept all types of radicals produced in cellular compartments with synergistic mechanisms;
• Coenzyme Q10, a fundamental element for perfecting the synergy with vitamins for its antioxidant action;
• NADH, coenzyme with oxide-reducing activity, cofactor of antioxidant enzymes;
• L-selenomethionine containing Selenium, an essential element in multiple biochemical reactions and involved in the recycling of oxidized glutathione, essential in the respiratory chain for the production of energy where it also has an antioxidant activity.
• Presence of olive oil containing polyphenols, whose activity for human health has now been proven by centuries of history and the epidemiology of longevity.

ANTIOX advance also has health claims approved by EFSA (European Food and Safety Agency) such as:

• Vitamins C and E and Selenium contribute to the protection of cells from oxidative stress.
• Vitamin C contributes to the reduction of the sense of tiredness and fatigue.
• Vitamin C and Selenium contribute to the normal functioning of the immune system.
• Vitamin C and Selenium contribute to the normal maintenance of skin, nails and hair.
• Astaxanthin is an antioxidant.

With a careful molecular choice, ANTIOX advance allows intervention on all the operating modes of the antioxidant circuits, with balanced dosages to avoid excesses of antioxidant supplementation. A formulation in practical SOFT GEL capsules ensures optimal intestinal absorption and bio distribution.

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Bibliography:

1. Compendium of Chemical Terminology, 2nd ed. (the “Gold Book”). Compiled by A. D. McNaught and A. Wilkinson. Blackwell Scientific Publications, Oxford (1997). Online version (2019-) created by S. J. Chalk. ISBN 0-9678550-9-8. https://doi.org/10.1351/goldbook.
2. Membrana cellulare e lipidomica. Carla Ferreri e Chryssostomos Chatgilialoglu. 2014, CNR Edizioni
3. Solomons TWG, Chimica organica, a cura di G. Ortaggi, D. Misiti, 2ª ed., Zanichelli, 1988, ISBN 88-08-09414-6.
4. Muller FL, Lustgarten MS, Jang Y, Richardson A, Van Remmen H. Trends in oxidative aging theories. Free Radic Biol Med. 2007 Aug 15;43(4):477-503. doi: 10.1016/j.freeradbiomed.2007.03.034. Epub 2007 Apr 10. PMID: 17640558.
5. Regolamento (UE) n. 432/2012 della Commissione, del 16 maggio 2012, relativo alla compilazione di un elenco di indicazioni sulla salute consentite sui prodotti alimentari, diverse da quelle facenti riferimento alla riduzione dei rischi di malattia e allo sviluppo e alla salute dei bambini.
6. Decreto MinSal. 26/07/2019 – Disciplina dell’impiego negli integratori alimentari di sostanze e preparati vegetali.

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Article by the Editorial Group of Lipinutragen

The information given should in no way replace the direct relationship between health professional and patient.

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