Antioxidant

Antioxidants and Aging

We hear about the benefits of antioxidants every day. But who are they exactly? And why are they so essential to our health?

Antioxidants are primarily preventive. They protect the body at the cellular level, primarily against free radical damage, which is released by cells during the normal functioning of our bodies.

So far, so good: A healthy, functioning body emits potentially harmful entities, but these are detected and neutralized by our cells. Cells are therefore our first line of defence, protecting and repairing our biological systems [4]. These defence mechanisms are extremely complex and involve many molecules, which are called Antioxidants because they fight against the oxidizing (destructive) power of free radicals. In particular, they are involved in a multitude of "redox" cycles (a cascade of oxidation-reduction reactions). Our body produces many Antioxidants directly, such as superoxide dismutase (SOD), glutathione peroxidase, coenzyme Q10...

Unfortunately, over time and due to external factors such as pollution, UV rays, diet... these harmful free radicals can become too numerous and overwhelm the antioxidant mechanisms of the cells. Especially since at the same time, our production of these antioxidant molecules declines, the redox cycles are disrupted, our defences become less efficient... This is precisely what we call "ageing". 1,2].

Nine brands have thus been proposed as the imprint of ageing. These can directly affect our genetic material, i.e. our DNA (genomic instability, reduction of the sites at the base of our chromosomes - the famous telomeres - epigenetic alterations), our protein balance (functional properties of proteins), our nutrient sensitivity mechanisms, our mitochondrial functions, our cell renewal and regeneration processes, and finally, our cellular communication mechanisms [3].

Focus on a mark of aging: the skin

During physiological aging, the appearance and structure of our skin are particularly affected (notably less collagen: appearance of wrinkles and loss of elasticity). Below the surface, at the cellular level, our skin also becomes more sensitive to environmental "aggressions" (UV rays, toxins, pollution...), and less effective in combating oxidative stress (emission of the famous free radicals). The visible signs of ageing are then likely to become more apparent and more numerous, and may even induce changes in composition, structure, elasticity and pigmentation [7,8]. This explains why the skin is a major site of antioxidant activity in the human body.

If the body no longer sufficiently manages free radicals to protect cells, and in order to limit the phenomena of ageing, it should therefore be supported by an external supply of dietary antioxidants or Nutraceuticals. This is particularly important for the skin [9,10].

But which Nutraceutical Antioxidants to choose ?

Until today the approach of "antioxidant" products has always been the same: to bring by oral vision a molecule that will "capture" free radicals. The idea being that as we age, we produce fewer free radical scavengers, so we can provide them directly. So you can imagine the shallot race, with the aim of finding the most powerful antioxidant, the one that will capture the maximum of free radicals. All of this, of course, measured by a laboratory test under totally artificial conditions (ORAC test and ORAC index). If this strategy seems intuitively interesting, it has two major flaws:

1. The cause is not tackled but the consequences. Indeed, the decline in antioxidant production is a direct result of cellular aging, primarily at the genomic level. We do not take into account the complexity of the body's antioxidant mechanisms. Each of these antioxidants acts within a collective, in Redox cycles (a cascade of oxidation and reduction reactions). Bringing just one element among the many molecules involved is at best useless, at worst harmful (because it can disturb the balance of these Redox cycles).

And we don't even mention all these supposedly overpowering antioxidants whose stability or bioavailability leaves something to be desired (have you ever heard of Glutathione?). They sell you an antioxidant with an ORAC number that's going through the roof? Ask yourself a simple question: OK, it works great in the lab, on a probe, but what happens in the body is a whole different story, much more complex: so where is the clinical data?

By targeting the causes of ageing rather than the consequences, a new approach is possible. This approach allows the body to maintain its own defence systems and the balance of its antioxidant mechanisms. This requires molecules that act at the genomic level, protecting telomeres and gene expression (epigenetics).

And in order to design a truly effective antioxidant in capsules, it is also necessary to control these parameters:

• Understanding the mechanism of action,
• Guaranteed bioavailability and stability,
• Effectiveness demonstrated by clinical studies.

So how did we do ?

Sulforaphane - the "star" antioxidant of the scientific community

While broccoli is not the most well-known antioxidant food, researchers have been studying the effects of a fascinating small molecule extracted from it for many years: Sulforaphane. The interest of the scientific community in the beneficial effects of Sulforaphane has increased particularly in the last 10 years. Its protective effect against the ageing process is now rather well established thanks to its powerful antioxidant role with nutrigenomic properties, thus getting to the root of the problem (action on gene expression) [15]. Sulforaphane is capable of - activating phase II enzymes responsible for the antioxidant response and metabolism of xenobiotics (toxic compounds such as reactive oxygen species): "detoxification pathway" and - inhibiting phase I enzymes, enzymes responsible for the activation of xenobiotics. It is also capable of inhibiting the processes involved in the pro-inflammatory response (NF-κB pathway). Finally, Sulforaphane may be able to inhibit epigenetic processes by which the expression of our genes is modified and to protect our protein system by protecting its activities and functions [16,17]. One of the latest publications on the scientific work carried out on Sulforaphane reports that its beneficial effects would be observable as early as 1.8 mg of pure Sulforaphane per day [18].

Clinical efficacy and mechanism of action are therefore validated. What about bioavailability ?

When consuming foods rich in Sulforaphane precursors (cruciferous plants, cabbage, broccoli) and after an enzymatic action of myrosinase, the precursor called glucoraphanin is hydrolyzed into Sulforaphane from the microbiota of the small intestine.

Today and after a necessary development period of more than 20 years (!), the Sulforaphane is still very unstable. !!), the direct use of Sulforaphane is finally possible and in optimal conditions guaranteeing its bioavailability AND stability, through the introduction of Sulfodyne® (from broccoli) in our Antioxidant. This unique and Made In France innovation has led to the filing of 2 patents. So for the first time a broccoli extract, standardized in Sulforaphane, ticks all the boxes of nutraceutical efficacy:

• Mechanism of action ☑︎
• Bioavailability ☑︎
• Clinical efficacy ☑︎

To give you some benchmarks for comparison:

• 2 capsules of our Antioxidant provide as much Sulforaphane as 190g of raw broccoli daily.
• Numerous broccoli extracts are available and praise its antioxidant power. However, these extracts contain at best only precursors of Sulforaphane, with extremely low or even zero conversion depending on the person. If you are promised glucoraphanin - and count 25 mg of this precursor to have 1 mg of Sulforaphane in the best case ...

Polyphenols extracted from grape seeds

Grape extracts are naturally rich in polyphenols including anthocyanins, flavonols, stilbenes (including resveratrol) and phenolic acids. Different polyphenol profiles exist depending on the part of the grape used. The seeds contain the highest percentage of active polyphenols: flavonols and anthocyanins [19], giving these polyphenol-rich extracts a high antioxidant potential [20]. Although the mechanisms of action are difficult to elucidate, grape polyphenols could have a positive influence on telomere length and those present in the seeds could protect DNA integrity (fighting DNA damage) by effectively participating in the elimination of free radicals [21,22]. The structure of polyphenols should be considered for optimal efficacy. Indeed, 82% of flavonol monomers would be absorbed, against only 1% for polymers, ensuring better distribution to body tissues. Epicatechin (flavonol monomer), whose bioavailability is high, is notably present in significant quantities (≥ 20%) in the selected extract: GRAP'INSIDEâ. So you can understand why we have selected this particular extract.

• Mechanism of action ☑︎
• Bioavailability ☑︎
• Clinical efficacy ☑︎

Coenzyme Q10 (Q10)

CoQ10, also known as ubiquinone or coenzyme Q10, is a central compound involved in mitochondrial electron transport and thus in energy production and membrane activity [23]. During the aging process, the biosynthesis of CoQ10 by the body decreases. The additional CoQ10 supply could therefore influence oxidative damage to the core molecules of our cells and functions: lipids, proteins and DNA [24,25]. The "ideal" doses of CoQ10 applicable for an "anti-aging" cure would be difficult to define, but studies report that as early as 100mg per day, the effects would be noticeable [24,26]. Moreover, these beneficial effects are often blocked by the difficulties of CoQ10 to reach the blood circulation when taken orally. This is why complexation with cyclodextrins allows CoQ10 to become soluble and therefore bioavailable [27,28]. Thanks to the CavaQ10 complex, a process of encapsulation of CoQ10 (ubiquinone, stable form) in cyclodextrins, bioavailability becomes 18 times higher than that of the compound alone. Considering that CavaQ10 contains 20% CoQ10 and that its bioavailability is 18 times higher, our Antioxidant therefore provides the equivalent of 360mg of CoQ10 for 2 capsules. Here again:

• Mechanism of action☑︎
• Bioavailability ☑︎
• Clinical efficiency ☑︎

Publications

1. Barouki, R. Stress oxydant et vieillissement. médecine/sciences 2006, 22, 266–272, doi:10.1051/medsci/2006223266.
2. Bonnefont-Rousselot, D. Stress oxydant et vieillissement. 2007,
3. López-Otín, C.; Blasco, M.A.; Partridge, L.; Serrano, M.; Kroemer, G. The Hallmarks of Aging. Cell 2013, 153, 1194–1217, doi:10.1016/j.cell.2013.05.039.
4. Liguori, I.; Russo, G.; Curcio, F.; Bulli, G.; Aran, L.; Della-Morte, D.; Gargiulo, G.; Testa, G.; Cacciatore, F.; Bonaduce, D.; et al. Oxidative stress, aging, and diseases. Clin. Interv. Aging 2018, Volume 13, 757–772, doi:10.2147/CIA.S158513.
5. Conti, V.; Izzo, V.; Corbi, G.; Russomanno, G.; Manzo, V.; De Lise, F.; Di Donato, A.; Filippelli, A. Antioxidant Supplementation in the Treatment of Aging-Associated Diseases. Front. Pharmacol. 2016, 7, doi:10.3389/fphar.2016.00024.
6. Tan, B.L.; Norhaizan, M.E.; Liew, W.-P.-P.; Sulaiman Rahman, H. Antioxidant and Oxidative Stress: A Mutual Interplay in Age-Related Diseases. Front. Pharmacol. 2018, 9, 1162, doi:10.3389/fphar.2018.01162.
7. Rinnerthaler, M.; Bischof, J.; Streubel, M.; Trost, A.; Richter, K. Oxidative Stress in Aging Human Skin. Biomolecules 2015, 5, 545–589, doi:10.3390/biom5020545.
8. Dunaway, S.; Odin, R.; Zhou, L.; Ji, L.; Zhang, Y.; Kadekaro, A.L. Natural Antioxidants: Multiple Mechanisms to Protect Skin From Solar Radiation. Front. Pharmacol. 2018, 9, 392, doi:10.3389/fphar.2018.00392.
9. Addor, F.A.S. Antioxidants in dermatology. An. Bras. Dermatol. 2017, 92, 356–362, doi:10.1590/abd1806-4841.20175697.
10. Petruk, G.; Del Giudice, R.; Rigano, M.M.; Monti, D.M. Antioxidants from Plants Protect against Skin Photoaging. Oxid. Med. Cell. Longev. 2018, 11, doi:https://doi.org/10.1155/2018/1454936.
11. Guilland, J.-C. Les interactions entre les vitamines A, D, E et K : synergie et/ou compétition. Ol. Corps Gras Lipides 2011, 18, 59–67, doi:10.1051/ocl.2011.0376.
12. Dutra, M.T.; Martins, W.R.; Ribeiro, A.L.A.; Bottaro, M. The Effects of Strength Training Combined with Vitamin C and E Supplementation on Skeletal Muscle Mass and Strength: A Systematic Review and Meta-Analysis. J. Sports Med. 2020, 2020, 1–9, doi:10.1155/2020/3505209.
13. Nikolaidis, M.G.; Kerksick, C.M.; Lamprecht, M.; McAnulty, S.R. Does Vitamin C and E Supplementation Impair the Favorable Adaptations of Regular Exercise? Oxid. Med. Cell. Longev. 2012, 2012, 1–11, doi:10.1155/2012/707941.
14. Cory, H.; Passarelli, S.; Szeto, J.; Tamez, M.; Mattei, J. The Role of Polyphenols in Human Health and Food Systems: A Mini-Review. Front. Nutr. 2018, 5, 87, doi:10.3389/fnut.2018.00087.
15. Houghton, C.A. Sulforaphane: Its “Coming of Age” as a Clinically Relevant Nutraceutical in the Prevention and Treatment of Chronic Disease. Oxid. Med. Cell. Longev. 2019, 2019, 1–27, doi:10.1155/2019/2716870.
16. Juge, N.; Mithen, R.F.; Traka, M. Molecular basis for chemoprevention by sulforaphane: a comprehensive review. Cell. Mol. Life Sci. 2007, 64, 1105–1127, doi:10.1007/s00018-007-6484-5.
17. Santín-Márquez, R.; Alarcón-Aguilar, A.; López-Diazguerrero, N.E.; Chondrogianni, N.; Königsberg, M. Sulforaphane - role in aging and neurodegeneration. GeroScience 2019, 41, 655–670, doi:10.1007/s11357-019-00061-7.
18. Yagishita, Y.; Fahey, J.W.; Dinkova-Kostova, A.T.; Kensler, T.W. Broccoli or Sulforaphane: Is It the Source or Dose That Matters? Molecules 2019, 24, 3593, doi:10.3390/molecules24193593.
19. Xia, E.-Q.; Deng, G.-F.; Guo, Y.-J.; Li, H.-B. Biological Activities of Polyphenols from Grapes. Int. J. Mol. Sci. 2010, 11, 622–646, doi:10.3390/ijms11020622.
20. Ma, Z.; Zhang, H. Phytochemical Constituents, Health Benefits, and Industrial Applications of Grape Seeds: A Mini-Review. Antioxidants 2017, 6, 71, doi:10.3390/antiox6030071.
21. Yen, C.-Y.; Hou, M.-F.; Yang, Z.-W.; Tang, J.-Y.; Li, K.-T.; Huang, H.-W.; Huang, Y.-H.; Lee, S.-Y.; Fu, T.-F.; Hsieh, C.-Y.; et al. Concentration effects of grape seed extracts in anti-oral cancer cells involving differential apoptosis, oxidative stress, and DNA damage. BMC Complement. Altern. Med. 2015, 15, 94, doi:10.1186/s12906-015-0621-8.
22. Vidaček, N.Š.; Nanić, L.; Ravlić, S.; Sopta, M.; Gerić, M.; Gajski, G.; Garaj-Vrhovac, V.; Rubelj, I. Telomeres, Nutrition, and Longevity: Can We Really Navigate Our Aging? J. Gerontol. Ser. A 2018, 73, 39–47, doi:10.1093/gerona/glx082.
23. Hernández-Camacho, J.D.; Bernier, M.; López-Lluch, G.; Navas, P. Coenzyme Q10 Supplementation in Aging and Disease. Front. Physiol. 2018, 9, 44, doi:10.3389/fphys.2018.00044.
24. Varela-López, A.; Giampieri, F.; Battino, M.; Quiles, J. Coenzyme Q and Its Role in the Dietary Therapy against Aging. Molecules 2016, 21, 373, doi:10.3390/molecules21030373.
25. Barcelos, I.P. de; Haas, R.H. CoQ10 and Aging. Biology 2019, 8, 28, doi:10.3390/biology8020028.
26. Casagrande, D.; Waib, P.H.; Jordão Júnior, A.A. Mechanisms of action and effects of the administration of Coenzyme Q10 on metabolic syndrome. J. Nutr. Intermed. Metab. 2018, 13, 26–32, doi:10.1016/j.jnim.2018.08.002.
27. Terao, K.; Nakata, D.; Fukumi, H.; Schmid, G.; Arima, H.; Hirayama, F.; Uekama, K. Enhancement of oral bioavailability of coenzyme Q10 by complexation with γ-cyclodextrin in healthy adults. Nutr. Res. 2006, 26, 503–508, doi:10.1016/j.nutres.2006.08.004.
28. Bank, G.; Kagan, D.; Madhavi, D. Coenzyme Q 10 : Clinical Update and Bioavailability. J. Evid.-Based Complement. Altern. Med. 2011, 16, 129–137, doi:10.1177/2156587211399438.