药物形式：
| 服用形式 | 药物形式 | 服用频次 | | PO（口服） | L-谷胱甘肽 | 150mg/片， 3次/天 | | NAC | | 200mg/片 1次/天 | | subligual （舌下含服）? | | |
3周随机交叉实验、20个人
V1、V2、V3表示定期随诊
wash-out表示消除前面一种药物对后面的影响。（这样的好处是实验都发生于同一群样本身上）
P1、P2、P3中的P表示period?
本篇博客解释论文【1】
Cysteine is the limiting factor for GSH synthesis and its represents 33.6% of the GSH molecule
[24]
. Providing 200 mg of cysteine (commercial dosage) would be suffifi
cient for the body to
theoretically synthetize de novo up to 600 mg of GSH（200mg的半胱氨酸可以合成600mg的谷胱甘肽）
Each product was administered successively during three periods (P1, P2 and P3) of 21 days each. A wash-out period of 14 days was observed between each product. Six combinations of administration were possible: [NAC-PO-SL]; [NAC-SL-PO]; [PO-SL-NAC]; [PO-NAC-SL]; [SL-PO-NAC]; [SL-NAC-PO] (PO?
oral form of GSH; SL? sublingual form). Each combination was randomly assigned to volunteers at the inclusion, by respecting a minimum of three subjects per combination. Each period included three visits: V1; V2 (V1t
10
7
2 days) and V3 (V2
t
10
7
2 days). In total, each volunteer received two preliminary visits (pre-inclusion and inclusion) and nine visits during the protocol.
PO、NAC、sublingual排列组合（3*2*1=6种），每种组合随机分配至少3个志愿者。
Blood tests were realized at the beginning (visit 1, before taking
treatment), at the middle (visit 2) and at the end (visit 3) of every
period, for all the volunteers. At each visit, the following parameters were measured.
（服药前，就诊一次，治疗中期，就诊一次，治疗结束后，就诊一次）
The secondary outcomes contributed to estimate the oxidative stress status of the volunteers: plasma reduced thiols, vitamin E,Total Cholesterol, HDL-C, LDL-C and plasma triglycerides were also measured.（
次要结果有助于评估氧化损伤
志愿者的应激状态：血浆还原硫醇、维生素E、
总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇和血浆甘油三酯
）
Carryover effect?延滞效应
wash-out 洗脱期
wash-out是因为交叉实验设计的时候会有前面一段时间的
Carryover effect?，所以需要消除影响。
The comparative analysis of bioavailability between oral GSH and the sublingual form is summarized in
Tables 3
and
4
.（表3和表4总结了口服和舌下含服两种形式）
?(NAC, oral GSH or sublingual GSH)?is reported in Table 5.
下面这段是分析
A comparative analysis was performed: first by taking NAC as reference (comparison NAC vs oral GSH and NAC vs sublingual GSH) and second by comparing the oral GSH to the sublingual GSH form.
In the oral GSH group, the GSH/GSSG ratio was low at each time and significantly different at V3 (p?0.03) compared to the NAC group.
In the sublingual GSH group, this ratio tended to be high at each time and was statistically significant at V2 (p?0.03) compared to the NAC group.
Compared to the oral GSH group, the sublingual group exhibited a higher GSH/GSSG ratio, in particular at V3 (p?0.02).?
表6. 还原硫醇
表7 血浆中的维生素E
表8 脂质状态
这三张表用来表示志愿者的应激状态?
3.2.3. Adverse effects
Values of the plasma levels of CRPus and liver function markers at each visit for each treatment arm were reported in
Table 9
. Whatever the marker (hepatic status or ultra-sensitive CRP), no
signi
fifi
cant changes were reported. For all the markers monitored, values were always within the range of normality. All the dosage forms were very well tolerated and no adverse events were reported by the participants, whatever the treatment used.（没有重大不良副作用）
High levels of GSSG are indicative of periods of oxidative stress. The ratio GSH/GSSG is an important marker of redox status
In our study, the GSH/GSSG ratios in the NAC and sublingual GSH arms are significantly higher than oral GSH one. It seems that the sublingual GSH form is more useful than the oral form to improve this balance.（服用NAC和舌下模式的GSH/GSSG显著高于口服方式，很明显舌下方式明显好于口服）
High levels of GSSG are indicative of periods of oxidative stress. The ratio GSH/GSSG is an
important marker of redox status（
GSSG的高水平表明存在氧化应激期。GSH/GSSG的比率为氧化还原状态的重要标志
）
In our study, the GSH/GSSG ratios in the NAC and sublingual GSH arms are significantly higher than oral GSH one. It seems that the sublingual GSH form is more useful than the oral form to improve this balance.
One possible explanation of these results is that oral GSH undergoes partial hydrolysis and oxidation during the digestive process. Therefore, the liver has to synthetize de novo GSH from
precursors.
(在我们研究发现，NAC和舌下GSH含服的GSH/GSSG比率明显高于口服GSH。在改善这一点上，舌下含服GSH形式似乎比口服形式更有用对这些结果的一种可能解释是，口服GSH在消化过程中忍受部分水解和氧化过程因此，肝脏必须从肝脏中重新合成GSH前体。)
Reference：
【1】Effects of N-acetylcysteine, oral glutathione (GSH) and a novel sublingual form of GSH on oxidative stress markers: A comparative crossover study.
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