Edeas Marvin
Société Française des Anti-oxydants, 15 rue de la Paix, 75002 Paris, France.
J Soc Biol. 2009;203(3):271-80. doi: 10.1051/jbio:2009031. Epub 2009 Oct 16.
Since several decades anti-oxidants have been much studied, and scientists have tried to prove the preventive and curative effects in many chronic diseases. However, it is not uncommon to find highly contradictory clinical results, which may explain that consumers are less enthusiastic for anti-oxidants food supplements. First of all, definitions should be reviewed, such as that of free radicals (FR); all of them are not toxic. Some of them, such as nitric oxide, are necessary for the proper physiological functioning of the body, and eliminating them would be a mistake! However, other reactive oxygen species (ROS), which are not FR, are toxic, such as hydrogen peroxide. We have also redefined the oxidative stress, which it is not only the result of an imbalance between oxidants and anti-oxidants, but also the consequence of imbalance in the cellular redox status. The mechanisms of action, bioavailability, synergy and methods to determine the level of anti-oxidants are very sensitive topics, and it is crucial to study them if we want to obtain reliable clinical studies. Given the failure of clinical studies about anti-oxidant, we try to explain strategies which should be followed. First of all, the nature of the anti-oxidant is important; and an anti-oxidant from a natural origin must be preferred. Then, we proposed that the dose-effect was certainly responsible for the failure of tests. Indeed, doses administered in the studies was either too weak to obtain significant results, or too high, becoming pro-oxidative and eliminating the basal concentration of ROS (physiological role). Involvement of mitochondria and glycation are particularly discussed. Nutrigenomics and nutrigenetics are also discussed, which study the interactions between genetics and nutrition. Genetic polymorphism can explain the variable absorption of micronutrients. This concept leads to a truth believed by all scientists, namely the need to provide the right anti-oxidant, in adequate quantity, at the right place, at the right time and for a particular individual. To increase the anti-oxidant capacity of the body, the exogenous intake of anti-oxidants must be increased or the endogenous synthesis of anti-oxidants (SOD, GPX, GSH) must be stimulated. Targeting mitochondria and increasing their overall anti-oxidant defence system will be a challenge. Increasing the bioavailability of anti-oxidants and studying their passage through the blood-brain barrier must be also taken in consideration.
几十年来，抗氧化剂一直是大量研究的对象，科学家们试图证明其对多种慢性疾病的预防和治疗作用。然而，临床结果存在高度矛盾的情况并不罕见，这或许可以解释为什么消费者对抗氧化剂补充剂的热情不高。首先，应该重新审视一些定义，比如自由基（FR）的定义；并非所有自由基都是有毒的。其中一些，比如一氧化氮，对于身体的正常生理功能是必需的，消除它们将是一个错误！然而，其他一些并非自由基的活性氧（ROS）却是有毒的，比如过氧化氢。我们还重新定义了氧化应激，它不仅是氧化剂和抗氧化剂之间失衡的结果，也是细胞氧化还原状态失衡的后果。抗氧化剂的作用机制、生物利用度、协同作用以及测定其水平的方法都是非常敏感的话题，如果我们想要获得可靠的临床研究结果，对这些进行研究至关重要。鉴于抗氧化剂临床研究的失败，我们试图解释应该遵循的策略。首先，抗氧化剂的性质很重要；天然来源的抗氧化剂更应被优先选择。然后，我们提出剂量效应肯定是试验失败的原因。的确，研究中使用的剂量要么过低无法获得显著结果，要么过高，从而产生促氧化作用并消除了活性氧的基础浓度（生理作用）。特别讨论了线粒体和糖基化的作用。还讨论了营养基因组学和营养遗传学，它们研究基因与营养之间 的相互作用。基因多态性可以解释微量营养素吸收的差异。这个概念引出了所有科学家都认同的一个事实，即需要在正确的时间、为特定个体、在正确的地点提供适量的正确抗氧化剂。为了提高身体的抗氧化能力，必须增加抗氧化剂的外源摄入，或者刺激抗氧化剂（超氧化物歧化酶、谷胱甘肽过氧化物酶、谷胱甘肽）的内源性合成。针对线粒体并增强其整体抗氧化防御系统将是一项挑战。还必须考虑提高抗氧化剂的生物利用度以及研究它们通过血脑屏障的情况。
