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The clinical effect of glutathione on skin color and other related skin conditions: A systematic review
Journal of Cosmetic Dermatology
Abstract
Background
Glutathione is one of agents which is commonly used to lighten skin color in Asia as a dietary supplement. Previous studies suggest its potential effect of glutathione on skin color. However, the clinical efficacy of glutathione in oral form is still questionable due to its limited absorption and bioavailability.
Aim
To determine the clinical effects of glutathione on skin color and related skin conditions.
Patients/Methods
A systematic review was conducted using PubMed, CINAHL, Scopus, EMBASE and Cochrane library were searched from inceptions to October 2017. All clinical studies evaluating the effect of glutathione on any skin effects in healthy volunteer were included.
Results
A total of four studies were included. Three studies were RCTs with placebo control, while one was a single‐arm trial. One study used topical form, while others used oral form of glutathione with 250 to 500 mg/day. We found that both oral glutathione with the dosage of 500 mg/day and topical 2.0% oxidized glutathione could brighten skin color in sun‐exposed area measured by skin melanin index. No significant differences in the reduction in skin melanin index were observed in sun‐protected area for any products. In addition, glutathione also has a trend to improve skin wrinkle, skin elasticity, and UV spots. Some adverse events but nonserious were reported.
Conclusions
Current evidence of the skin whitening effect of glutathione is still inconclusive due to the quality of included studies and inconsistent findings. However, there is a trend that glutathione might brighten skin color at skin‐exposed area.
... Review papers which looked at the few available clinical trials have not offered any clear guidelines for the clinician seeking advice on best practice for the management of patients with hyperpigmentation. [11][12][13] We therefore decided to review the literature and try to correlate absorption routes, bioavailability and clinical effectiveness of glutathione to formulate some guidance for the practitioner trying to treat hyperpigmentation, in particular using the orobuccal route using newer methods like the oral dispersible film. The objective of this work was to bring together all scientific and patient-related data regarding oral absorption, dosage, and clinical effects in a fusion which has clinical relevance to serve as guidance for the clinician before more robust and well-designed trials can be conducted to provide the many answers which still elude us about this very promising treatment. ...
... 49 There are now several trials in the literature documenting a positive role of orally administered glutathione for the treatment of hyperpigmentation, despite its poor absorption. 6,7,12,13,33,40 Several review papers have tried to pull together evidence supporting the role of glutathione in reducing skin pigmentation. [11][12][13] Nearly all trials are conducted over shorter durations of time and there is no long-term data available on the effect of orally administered glutathione on skin pigmentation. ...
... 6,7,12,13,33,40 Several review papers have tried to pull together evidence supporting the role of glutathione in reducing skin pigmentation. [11][12][13] Nearly all trials are conducted over shorter durations of time and there is no long-term data available on the effect of orally administered glutathione on skin pigmentation. Long-term data is important in view of the fact that those individuals, predominantly women, who seek treatment need to be managed over longer periods of time to maintain effect and as part of their personal preference and self-esteem. ...
Treatment of dark skin with glutathione has become popular due to its depigmenting properties and low toxicity. Glutathione has been used topically, orally and parenterally in the management of dark skin. There are no clear published guidelines for management of skin pigmentation despite some clinical trials of shorter duration and small sample sizes. We examined published scientific and patient data to generate guidance for the clinician for managing hyperpigmentation using glutathione by orobuccal route. Various aspects of glutathione bioavailability were examined when administered by oral routes. Absorption of glutathione from the gastrointestinal tract is poor. Some trials have favored administering high oral doses to achieve therapeutic effect. General consensus remains against treatment of hyperpigmentation with glutathione by the oral route. Clinical and experimental evidence supporting significant glutathione absorption from orobuccal mucosa was examined. The latter is superior to the oral route since glutathione passes directly into systemic circulation resulting in a much higher rate of absorption compared to that achieved by oral intake. High blood levels thus achieved have therapeutic value. Treatment of hyperpigmentation with glutathione by the orobuccal route using hydroxypropyl cellulose (HPC) film was reviewed to formulate clinical guidance from published data. A future randomized, double-blind, placebo-controlled trial should study treatment of hyperpigmentation with glutathione using oral dispersible HPC film, with longer-term follow-up and larger sample size. This paper will hopefully offer broad guidance for the clinician on use of glutathione for hyperpigmentation management, until outcomes of larger, longer duration trials become available.
... 14 In contrast, Weschawalit et al 3 reported a statistically signi cant e ect of glutathione as a skin-lightening agent, but this was limited to a group of participants aged older than 40 years who received GSH, a reduced form of glutathione, on the sun-exposed area of the right forearm. 3 Arjinpathana et al 1 used a Mexameter® (Courage+Khazaka Electronic, Köln, Germany) to measure the melanin index as the main output parameter and found that glutathione was most e ective on sun-exposed skin. 1 In their systematic review, Dilokthornsakul et al 15 likewise reported that glutathione might lighten skin tone in sun-exposed areas; however, its skin-lightening e ects remain controversial due to con icting results from several clinical trials. 15 Our study results di ered from those of these studies, as glutathione O R I G I N A L R E S E A R C H supplement appeared in our investigation to have no signi cant positive e ects on sunexposed skin. ...
... Tsuji-Naito et al 27 demonstrated that DHLHZn (sodium zinc dihydrolipoyl histidinate, compound of Zn2+/dyhydrolipoic acid derivative complex, which was developed for cosmetic/medical use) serves as a potentially e ective skinlightening agent, an e ectiveness that is based on the compound's covalent scavenging of DOPAquinone, resulting in depigmentation. 27 Our study revealed that some mild adverse events occurred in the rst four weeks, although 15 reported that most adverse events were gastrointestinal tract symptoms or skin reactions. Skin reactions, including pruritus, erythema, and red spots, were also observed in the placebo group. ...
... Skin reactions, including pruritus, erythema, and red spots, were also observed in the placebo group. 15 With the development of analysis technology, such as pattern recognition from a digital image, facial skin measurement systems using a digital image have been developed, and Janus-III has become one of the most widely used facial skin measurement options in the skincare industry in Korea, owing to its convenience and diverse measuring characteristics. A study by Leem et al 28 demonstrated that the measured data of facial characteristics using the Janus-III system showed highly correlated patterns with those evaluated by a dermatologist. ...
Clinicaltrialsgov identifier:
NCT04105504.
Background:
For Asians, especially women with darker skin tones (Fitzpatrick Skin Types IV and V), clear, bright skin is considered highly desirable, and various topical, oral, or injection-based cosmetic skin-lightening agents with different mechanisms of action are widely available across Asia.
Objective:
We sought to investigate the efficacy and safety of an oral glutathione supplement comprising L-glutathione (fermentation), ascorbic acid, alpha-lipoic acid, and zinc (as zinc aspartate) as a skin-lightening agent.
Methods:
This randomized, double-blind, controlled clinical trial was carried out at three teaching hospital-based dermatovenereology clinics in Indonesia. Participants were randomized to receive either the glutathione supplement or placebo capsules and were evaluated every four weeks over a 12-week study period. Total reduction in spot ultraviolet, spot polarization, and skin tone were measured and recorded using a Janus Facial Analysis System® (PIE Co., Ltd, Suwon-si, Gyeonggi-do, Korea).
Results:
Eighty-three participants, aged between 33 and 50 years, completed the study. Reductions in spot ultraviolet in certain subgroups, spot polarization, and skin tone were greater in the glutathione supplement group than in the placebo group, but the difference was not statistically significant. Both the glutathione supplement and placebo groups experienced only mild side effects in the first four weeks.
Conclusion:
The oral glutathione supplement was slightly beneficial for skin lightening in particular subgroups, but the results were not statistically significant. Mild and temporary side effects were reported. Further research is required to more fully evaluate the efficacy of this glutathione supplement as a skin-lightening agent.
... play the main role in many metabolic processes polyunsaturated fatty acids (PUFAs) oxidizes by ROS in the cell membrane. This reaction will results in lipid peroxidation, that yields free radicals (7) . ...
... Newly, the advance has been made in understanding recurrent pregnancy loss approximately 10-15% of all first-time pregnancies bring about an unsuccessful miscarriage. In many instances, a similar miscarriage rate in subsequent pregnancies is expected (7) . Jaslow (17) and Rai (18). ...
Background: Pregnancy loss, also referred to as a miscarriage or spontaneous abortion, is generally defined as a nonviable intrauterine pregnancy up to 20 weeks gestation. Early pregnancy loss, which occurs in the first trimester, is the most common type.
... play the main role in many metabolic processes polyunsaturated fatty acids (PUFAs) oxidizes by ROS in the cell membrane. This reaction will results in lipid peroxidation, that yields free radicals (7) . ...
... Newly, the advance has been made in understanding recurrent pregnancy loss approximately 10-15% of all first-time pregnancies bring about an unsuccessful miscarriage. In many instances, a similar miscarriage rate in subsequent pregnancies is expected (7) . Jaslow (17) and Rai (18). ...
Background: Pregnancy loss, also referred to as a miscarriage or spontaneous abortion, is generally defined as a nonviable intrauterine pregnancy up to 20 weeks gestation. Early pregnancy loss, which occurs in the first trimester, is the most common type.
Objective: The aims of the study were to assess the role of (MDA, GSH, and levels of antioxidant vitamins, C, E and IgG, IgM of Toxoplasma gondii) causes of Abortions.
Materials and Method: For this study, 45 aborted women have been selected in first – trimester, and 25 well-matched women as control group their ages range from ( 20 – 33 years).
Results: The study shows is an increasing level of Malondialdehyde (MDA) in women with toxoplasmosis.
Furthermore, there is a decreasing level of antioxidant vitamins (A, C, and E), and Glutathione (GSH).
... play the main role in many metabolic processes polyunsaturated fatty acids (PUFAs) oxidizes by ROS in the cell membrane. This reaction will results in lipid peroxidation, that yields free radicals (7) . ...
... Newly, the advance has been made in understanding recurrent pregnancy loss approximately 10-15% of all first-time pregnancies bring about an unsuccessful miscarriage. In many instances, a similar miscarriage rate in subsequent pregnancies is expected (7) . Jaslow (17) and Rai (18). ...
Background: Pregnancy loss, also referred to as a miscarriage or spontaneous abortion, is generally defined as a nonviable intrauterine pregnancy up to 20 weeks gestation. Early pregnancy loss, which occurs in the first trimester, is the most common type.
... The HIFU procedure induced a warming sensation and vibration, which is hypothesized to enhance the absorption of the topical agent. Glutathione, a potent antioxidant, is known for its skin-whitening properties and anti-melanogenic effects, which impact melanin production (10)(11)(12). Hyaluronic acid, with its biodegradability and non-toxicity, functions primarily as a hydrating agent by binding water to tissue, thus improving skin hydration (6,9,13). ...
Background
High-intensity focused ultrasound (HIFU) is well-documented for skin rejuvenation, lifting, and tightening. However, its synergistic effects with topical agents, enhanced by HIFU-induced vibration and heat, remain underexplored.
Objective
To evaluate clinical and photographic outcomes of HIFU combined with a topical agent versus the topical agent alone.
Method
This non-randomized controlled trial involved 20 female volunteers (ages 30–55) divided into two groups. Group A (n = 10) received two HIFU sessions combined with a topical agent containing glutathione and hyaluronic acid. Group B (n = 10) received the topical agent alone. Outcomes were assessed using digital photography, patient satisfaction surveys, and the A-One Smart™ system for fine wrinkles, hyperpigmentation, and hydration. Skin brightening was evaluated with the Global Esthetic Improvement Scale (GAIS).
Results
Group A showed significant reductions in fine wrinkles (6.25 ± 2.00 mm to 3.10 ± 1.62 mm), improved hyperpigmentation (3.50 ± 0.80 to 2.10 ± 1.05), and increased hydration (28 ± 10 to 55 ± 11) (all p < 0.05). Over two-thirds of Group A reported significant improvements, with no complications. Group B showed minimal, non-significant changes (p > 0.05), with only 30% reporting noticeable improvements.
Conclusion
Combining HIFU with a topical agent significantly enhances skin quality and brightness without adverse effects.
... The dose of Glutathione use in all three routes recommended by dermatologists in our study is similar to the clinical trials that have been previously conducted. 9,23 In a study conducted by Weschawalit et. al (2017), patients were given a dose of 250mg/day. ...
Glutathione is one of the non-enzymatic antioxidants that is also involved in regulation of cellular proliferation and apoptosis. The application of Glutathione for skin lightening and depigmentation in dermatology started after discovery of its anti-melanogenic properties. There is still a lack of evidence regarding its patient population, dosage schedule, and safety on long-term use. The objective of this study is to analyze the usage pattern of Glutathione from dermatologists in India based on their clinical experience.
Questionnaire-based cross-sectional study conducted amongst dermatologists to understand indications, administration, safety, and adverse events associated with Glutathione therapy. Data entry was done in Microsoft Excel and descriptive statistics was applied.
Seventy-one responses were collected with the average experience of dermatologists being 5.24 + 7.32 years. 52.11% of these dermatologists routinely prescribe Glutathione therapy. The most common use is skin lightening given through the oral route. The preferred dose for oral route is 250mg given twice daily empty stomach for 4 weeks, topical route is 2% (w/w) applied once daily for 10 weeks, and intravenous route is 1200mg injection given weekly over 30 minutes. Only 3 out of 37 prescribing doctors have seen side effects. 54% of dermatologists feel that there is insufficient safety data available for this therapy.
This study shows the current practices of Glutathione therapy by dermatologists while also pointing to the need for more studies to be done with a larger sample size for a longer duration so that the use is standardized with improved safety.
... Ascorbic Acid (Vitamin C) Reduces hyperpigmentation, stimulation of collagen formation, wound healing, acts as an anti-inflammatory, and anti-wrinkle [98][99][100][101][102] Tocopherol (Vitamin E) Treatment for atopic dermatitis, anti-photoaging, skin dryness treatment products, anti-aging, antibacterial, anti-inflammatory, and anti-cancer [103][104][105] Resveratrol Wound healing, anti-aging, anti-pigmentation, anti-photoaging, treating dermatitis, and skin cancer [106][107][108][109] Coenzyme Q10 (Ubiquinone) Anti-aging, anti-inflammatory, and photoprotective [110][111][112][113][114] Ferulic Acid Anti-aging, photoprotective, and wound healing [76,115,116] Alpha-Lipoic Acid Anti-nanomaterial-induced toxicity, anti-aging, and anti-wrinkle [117][118][119][120] Glutathione Skin whitening [94,[121][122][123][124][125] Niacinamide (Vitamin B3) Treatment of cancer, blistering disorders, acne vulgaris, psoriasis, wound healing, pigmentation disorders, skin brightening, anti-aging properties, skin barrier protection, and skin regeneration [126][127][128][129][130][131][132] Retinol (Vitamin A) Anti-aging, anti-photodamage, anti-wrinkle, and wound healing [133][134][135][136][137][138] Lycopene Maintain skin integrity, treating AD, moisturize skin, anti-aging, and photoprotective [139][140][141][142] Beta-Carotene Photoprotective, moisturizing, and protects skin integrity [143][144][145][146][147][148][149] Caffeic Acid Anti-photoaging, anti-photodamage, and promotes collagen production [150][151][152][153][154] Ellagic Acid Anti-aging, photoprotection, and skin lightening [95,[155][156][157][158] Quercetin Photoprotection and anti-aging [55,68,159,160] Astaxanthin Photoprotective, anti-aging, anti-wrinkle, skin hydration, wound healing, anti-cancer properties, and anti-eczema effects [161][162][163][164][165][166][167] Studies have highlighted the benefits of antioxidants in skin and hair care, emphasizing their role in protecting against oxidative stress and aging. Vitamin E and selenium are particularly noted for their protective effects [168]. ...
The burgeoning interest in natural components in personal care products has led to significant research and development of ingredients such as plant extracts, antioxidants, peptides, and probiotics. These components have been recognized for their potential to enhance skin health through various mechanisms, addressing consumer demand for products that are both effective and benign. Plant extracts, known for their rich composition of bioactive compounds, offer a myriad of benefits including antioxidant, anti-inflammatory, and antimicrobial properties, making them invaluable in skin care formulations. Antioxidants, derived from both plants and other natural sources, play a pivotal role in protecting the skin from oxidative damage, thereby preventing premature aging and promoting skin vitality. Bioactive peptides have garnered attention owing to their multifunctional activities that include promoting collagen synthesis, inhibiting enzymes responsible for skin degradation, and reducing inflammation, thereby contributing to skin regeneration and anti-aging. Probiotics have expanded their utility beyond gut health to skin care, where they help in maintaining skin microbiome balance, thus enhancing skin barrier function and potentially mitigating various skin disorders. The purpose of this review is to explore the individual roles of plant extracts, antioxidants, peptides, and probiotics in personal care products, while emphasizing their synergistic effects when combined. By integrating these natural components, this paper aims to highlight the potential for developing innovative skincare formulations that not only address specific skin concerns but also contribute to overall skin health, aligning with the increasing consumer preference for natural and holistic skincare solutions.
... 16 In addition, GSH is also commonly used in cosmetic formulations for skin-lightening purposes, because it can scavenge free radicals and inhibit the activation of tyrosinase. 17,18 Importantly, nattokinase is the most special component identi- fermentation. Recently, nattokinase has been suggested to suppress endothelial inflammation and increase autophagy in mice. ...
Background
Skin aging is one of the most abundant aging‐related disorders that can be accelerated by excessive exposure to ultraviolet irradiation. Topically applied fermented skincare ingredients have gained mounting attentions due to their high concentration of various skin nourishing nutrients and bioactive components and low skin irritation potency.
Aims
In the present study, we aim to fully demonstrate the skin‐related benefits of a novel extract of Thermus thermophilus and Bacillus subtilis mixed‐culture ferment (TBFE).
Methods
TBFE was prepared through an innovative mixed‐culture fermentation process. The contents of nutrients and bioactive ingredients were quantified by different methods accordingly. Both in vitro tests and randomized controlled human trial were utilized to further demonstrate multifaceted beneficial effects on human skin, as well as the potential mechanisms.
Results
Our results showed that TBFE upregulated the expression of type IV collagen, elastin, aquaporin‐3, and dermal‐epidermal junction markers, while inhibited production of melanin, in different skin cell models. Moreover, TBFE inhibited the generation of reactive oxygen species and pro‐inflammatory mediators induced by ultraviolet irradiation in normal human keratinocytes, while stimulated autophagy in senescent keratinocytes. Results from clinical studies confirmed those in vitro findings, demonstrating that TBFE at 5% and 20% concentration provides anti‐aging properties in subjects with sensitive skin, in terms of improving wrinkles, moisturization, and skin lightening.
Conclusions
In summary, we demonstrate that a novel mixed‐culture ferment extract has promising anti‐aging effects, which may be attributed to anti‐oxidation, anti‐inflammation, and promotion of autophagy in skin cells.
... 7 Sementara itu, glutathione yang telah dikenal sebagai agen pencerah kulit, bekerja sebagai anti-melanogenik dengan mengurangi produksi melanin, sebagai antioksidan, antikerut, dan anti-penuaan. 8 Akan tetapi, pada laporan kasus ini tidak dilakukan penanganan komponen vaskular pada HPO yang seharusnya dilakukan laser vaskular, seperti pulsed dye laser dan long pulsed 1064nm Nd;YAG laser. ...
Pendahuluan: Hiperpigmentasi periorbital (HPO) merupakan kondisi yang mengganggu secara kosme- tik, ditandai dengan pigmentasi yang terutama pada kelopak mata bagian bawah. Hiperpigmentasi periorbital sulit untuk diobati dan terbatasnya pilihan terapi yang dapat diandalkan karena patogenesis dan etiologinya yang kompleks. Ilustrasi Kasus: Kami melaporkan dua orang wanita dengan hiperpigmentasi infraorbital yang diterapi dengan kombinasi polideoksiribonukleotida (PDRN), asam hialuronat cross-linked, dan glu- tathione melalui injeksi intradermal di area infraorbital kanan dan aplikasi menggunakan microneedling di area infraorbital kiri, total dua sesi perawatan dengan interval satu minggu. Diskusi: Pengobatan HPO ha- rus dimodifikasi sesuai dengan etiologinya, seperti pigmentasi, vaskular, perubahan kulit, dan tipe campuran. Polideoksiribonukleotida menyebabkan induksi dari sekresi faktor pertumbuhan, sitokin anti-inflamasi, per- baikan jaringan, penyembuhan luka, dan anti-melanogenik. Asam hialuronat cross-linked bekerja sebagai an- tioksidan, pelembab, penginduksi kolagen, dan biomaterial untuk penyembuhan luka. Sedangkan glutathione merupakan bahan pencerah kulit yang bekerja dengan mengurangi produksi melanin, sebagai antioksidan, dan anti-keriput. Kesimpulan: Kombinasi PDRN, asam hialuronat cross-linked, dan glutathione efektif mengobati HPO tipe pigmentasi. Penggunaan injeksi intradermal dan aplikasi jarum mikro sama efektifnya dengan peng- hantaran obat intradermal.
... Furthermore, UV radiation can induce oxidative stress [11], which leads to the formation of oxidants such as nitric oxide [12] and which indirectly stimulates skin pigmentation. Therefore, certain antioxidants can decrease melanin production, such as glutathione [13], ascorbic acid (ASA) [14], and ferulic acid [15]. Recently, researchers have combined tyrosinase inhibitors and antioxidants, to treat pigmented lesions. ...
Excessive melanin deposition in the skin leads to various skin pigmentation diseases, such as chloasma and age spots. The deposition is induced by several factors, including tyrosinase activities and ultraviolet-induced oxidative stress. Herein, we propose a multi-component, multi-pathway drug combination, with glabridin, 3-O-ethyl-L-ascorbic acid, and tranexamic acid employed as, respectively, a tyrosinase inhibitor, an antioxidant, and a melanin transmission inhibitor. Considering the poor skin permeability associated with topical application, dissolving microneedles (MNs) prepared with hyaluronic acid/poly(vinyl alcohol)/poly(vinylpyrrolidone) were developed to load the drug combination. The drug-loaded microneedles (DMNs) presented outstanding skin insertion, dissolution, and drug delivery properties. In vitro experiments confirmed that DMNs loaded with active ingredients had significant antioxidant and inhibitory effects on tyrosinase activity. Furthermore, the production of melanin both in melanoma cells (B16-F10) and in zebrafish was directly reduced after using DMNs. Clinical studies demonstrated the DMNs’ safety and showed that they have the ability to effectively reduce chloasma and age spots. This study indicated that a complex DMN based on a multifunctional combination is a valuable depigmentation product worthy of clinical application.
... The last finding suggests that there are area-specific genetic effects of the studied polymorphisms of the GCLC gene that may be a ributed to inter-individual differences in gene expression and, therefore, rates in glutathione biosynthesis by the skin from different body areas, as was demonstrated with regard to the rate of glutathione conjugation in different organs [66]. It is also known that the levels of glutathione may vary in sun-exposed and sun-protected areas [67], suggesting that UV exposure may impact glutathione biosynthesis in the skin. ...
The aim of this pilot study was to investigate whether single nucleotide polymorphisms (SNP) in the gene encoding the catalytic subunit of glutamate cysteine ligase (GCLC) are associated with the risk and clinical features of psoriasis. A total of 944 unrelated individuals, including 474 patients with a diagnosis of psoriasis and 470 healthy controls, were recruited for the study. Six common SNPs in the GCLC gene were genotyped using the MassArray-4 system. Polymorphisms rs648595 (OR = 0.56, 95% CI 0.35–0.90; Pperm = 0.017) and rs2397147 (OR = 0.54, 95% CI 0.30–0.98; Pperm = 0.05) were associated with susceptibility to psoriasis in males. In the male group, diplotype rs2397147-C/C × rs17883901-G/G was associated with a decreased risk of psoriasis (FDR-adjusted p = 0.014), whereas diplotype rs6933870-G/G × rs17883901-G/G (FDR-adjusted p = 0.045) showed an association with an increased disease risk in females. The joint effects of SNPs with tobacco smoking (rs648595 and rs17883901) and alcohol abuse (rs648595 and rs542914) on psoriasis risk were observed (Pperm ≤ 0.05). We also found multiple sex-independent associations between GCLC gene polymorphisms and various clinical features such as earlier disease onset, the psoriatic triad, and specific localizations of skin lesions. The present study is the first to show that polymorphisms of the GCLC gene are significantly associated with the risk of psoriasis and related to its clinical features.
... These findings suggest area-specific genetic effects of the studied polymorphisms of the GCLC gene that may be attributed to inter-individual differences in gene expression and therefore rates in glutathione biosynthesis by the skin from different body areas, as was demonstrated with regard to the rate of glutathione conjugation in different organs [66]. It is also known that the levels of glutathione may vary in sun-exposed and sun-protected areas [67], suggesting that UV exposure may impact glutathione biosynthesis in the skin. ...
The aim of this pilot study was to investigate whether single nucleotide polymorphisms (SNP) in the gene encoding the catalytic subunit of glutamate cysteine ligase (GCLC) are associated with the risk and clinical features of psoriasis. A total of 944 unrelated individuals, including 474 patients with a diagnosis of psoriasis and 470 healthy controls, were recruited for the study. Six common SNPs in the GCLC gene were genotyped using the MassArray-4 system. Polymorphisms rs648595 (OR=0.56 95%CI 0.35-0.90, Pperm=0.017) and rs2397147 (OR=0.54 95%CI 0.30-0.98, Pperm=0.05) were associated with susceptibility to psoriasis in males. In the male group, diplotype rs2397147-C/C×rs17883901-G/G was associated with decreased risk of psoriasis (FDR-adjusted P=0.014), whereas diplotype rs6933870-G/G×rs17883901-G/G (FDR-adjusted P=0.045) showed association with increased disease risk in females. Joint effects of SNPs with tobacco smoking (rs648595 and rs17883901) and alcohol abuse (rs648595 and rs542914) on the risk of psoriasis were observed (Pperm≤0.05). Furthermore, we found multiple sex-independent associations between GCLC gene polymorphisms and various clinical features such as earlier disease onset, the psoriatic triad, and specific localizations of skin lesions. The present study is the first to show that polymorphisms of the GCLC gene are significantly associated with the risk of psoriasis and related to its clinical features.
... 126 Whilst glutathione is often marketed as a safe treatment, studies regarding its use for skin lightening are lacking, with the majority of studies having limitations including small sample sizes, short study durations, short follow-up periods and the lack of glutathione bioavailability. 127,128 In addition, the use of IV glutathione has been associated with several complications, including Stevens-Johnson syndrome, abdominal pain, kidney dysfunction, brain toxicity and liver dysfunction. 127 Given the lack of research regarding its use, glutathione is not currently recommended for the treatment of melasma or PIH. ...
Hyperpigmentation disorders, such as post-inflammatory hyperpigmentation and melasma, are common conditions affecting all skin types. These conditions are largely benign and are influenced by numerous endogenous and exogenous factors impacting melanocyte activity and melanin production. Current treatment modalities for these conditions fall into broad categories, including photoprotection, topical and systemic therapies, chemical peels, and laser or light-based therapies. Biological differences in skin of colour require additional consideration when deciding on treatment and management. This narrative review provides an inclusive summary of these conditions and compares the current treatment options with a specific focus on skin of colour. Photoprotection and sunscreens protective against both UV and visible light are recommended for all individuals. Topical therapy is the recommended first-line treatment, with the gold standard being hydroquinone, which can be used alone or in combination with other agents. Chemical peels and laser or light-based therapies are also effective adjunctive methods of treatment; however, caution should be taken when used in patients with richly pigmented skin due to the increased risk of post-inflammatory hyperpigmentation. © 2022 Moolla S, Miller-Monthrope Y. Published by Drugs in Context.
... Se ha administrado por vía oral o intravenosa para disminuir la pigmentación cutánea y el fotoenvejecimiento. Dos recientes revisiones sistemáticas de la literatura, que incluyeron 3 ECA, no encontraron evidencia suficiente para recomendar su utilización en este contexto 50,51 . ...
Resumen
El envejecimiento cutáneo es influenciado por factores intrínsecos y extrínsecos, y múltiples mecanismos patogénicos están involucrados. Los tratamientos utilizados en la actualidad son mayoritariamente tópicos o procedimientos mínimamente invasivos. La evidencia sobre la utilidad de la terapia sistémica es limitada: los estudios son en su mayoría de pequeño tamaño, de reducida duración, incluyen mayoritariamente a mujeres, la metodología de evaluación es heterogénea y no hay parámetros consensuados de respuesta clínica relevante. Además, los suplementos/fármacos sistémicos no están exentos de efectos adversos. El colágeno hidrolizado oral y el ácido hialurónico oral son bien tolerados y múltiples ensayos clínicos muestran que pueden mitigar algunos signos de envejecimiento cutáneo. La isotretinoína oral en dosis bajas es otra alternativa, pero con un mayor potencial de efectos adversos. Múltiples suplementos como vitaminas, flavonoides, diversos extractos de plantas y oligoelementos presentan escasa evidencia clínica. El futuro del manejo del envejecimiento cutáneo pareciera ser el tratamiento con agentes senolíticos/senomórficos dirigidos específicamente contra células cutáneas senescentes.
... [27] Arbutin, kojic acid, fruit acid, and glutathione can inhibit tyrosinase, thereby reducing the synthesis of melanin by melanocytes, [28] and glutathione can be hydrolyzed to cysteine, which predisposes the melanin synthesis pathway to the production of lighter-colored melanin. [29] Additionally, vitamin C can reduce dopamine quinone to dopamine, which blocks the oxidation chain of melanin production and inhibits the formation of melanin. The LC-MS/MS analysis showed that the contents of 70 components in S3 were higher than those in the S1 and S2. ...
Ganoderma lucidum possesses anti-inflammatory, antioxidant, and immunomodulatory properties. We evaluated the anti-inflammatory and anti-melanogenesis effects of G. lucidum alone (S1), G. lucidum and Polygonatum odoratum (S2), and G. lucidum and P. ginseng (S3) using an ultraviolet B-irradiated HaCaT cell model and a prostaglandin 2 (PGE2)-treated B16-F10 melanocyte model. S3 inhibited PGE-2 and LL-37 secretion in HaCaT cells and melanin and tyrosinase expression in B16-F10 cells. Furthermore, LC/MS/MS results revealed that the levels of 70 components were higher in S3 than in S1 and S2. These results demonstrate that G. lucidum and P. ginseng co-culture fermentation broth possess in vitro anti-inflammatory and anti-melanogenesis effects; it can be used in the skin care industry.
... Se ha administrado por vía oral o intravenosa para disminuir la pigmentación cutánea y el fotoenvejecimiento. Dos recientes revisiones sistemáticas de la literatura, que incluyeron 3 ECA, no encontraron evidencia suficiente para recomendar su utilización en este contexto 50,51 . ...
Resumen
El envejecimiento cutáneo es influenciado por factores intrínsecos y extrínsecos, y múltiples mecanismos patogénicos están involucrados. Los tratamientos utilizados en la actualidad son mayoritariamente tópicos o procedimientos mínimamente invasivos. La evidencia sobre la utilidad de la terapia sistémica es limitada: los estudios son en su mayoría de pequeño tamaño, de reducida duración, incluyen mayoritariamente a mujeres, la metodología de evaluación es heterogénea y no hay parámetros consensuados de respuesta clínica relevante. Además, los suplementos/fármacos sistémicos no están exentos de efectos adversos. El colágeno hidrolizado oral y el ácido hialurónico oral son bien tolerados y múltiples ensayos clínicos muestran que pueden mitigar algunos signos de envejecimiento cutáneo. La isotretinoína oral en dosis bajas es otra alternativa, pero con un mayor potencial de efectos adversos. Múltiples suplementos como vitaminas, flavonoides, diversos extractos de plantas y oligoelementos presentan escasa evidencia clínica. El futuro del manejo del envejecimiento cutáneo pareciera ser el tratamiento con agentes senolíticos/senomórficos dirigidos específicamente contra células cutáneas senescentes.
... 126 Whilst glutathione is often marketed as a safe treatment, studies regarding its use for skin lightening are lacking, with the majority of studies having limitations including small sample sizes, short study durations, short follow-up periods and the lack of glutathione bioavailability. 127,128 In addition, the use of IV glutathione has been associated with several complications, including Stevens-Johnson syndrome, abdominal pain, kidney dysfunction, brain toxicity and liver dysfunction. 127 Given the lack of research regarding its use, glutathione is not currently recommended for the treatment of melasma or PIH. ...
Hyperpigmentation disorders, such as post-inflammatory hyperpigmentation and melasma, are common conditions affecting all skin types. These conditions are largely benign and are influenced by numerous endogenous and exogenous factors impacting melanocyte activity and melanin production. Current treatment modalities for these conditions fall into broad categories, including photoprotection, topical and systemic therapies, chemical peels, and laser or light-based therapies. Biological differences in skin of colour require additional consideration when deciding on treatment and management. This narrative review provides an inclusive summary of these conditions and compares the current treatment options with a specific focus on skin of colour. Photoprotection and sunscreens protective against both UV and visible light are recommended for all individuals. Topical therapy is the recommended first-line treatment, with the gold standard being hydroquinone, which can be used alone or in combination with other agents. Chemical peels and laser or light-based therapies are also effective adjunctive methods of treatment; however, caution should be taken when used in patients with richly pigmented skin due to the increased risk of post-inflammatory hyperpigmentation.
... Although no single GSH-containing preparation has been approved by the FDA as a therapeutic agent, many GSH supplements have already been available on the current market in different forms, such as injections [58], lozenges [59], oral sprays [60], oral liquids [61] and oral capsules [62]. Moreover, several studies have been performed to evaluate the therapeutic potential of GSH in different formulations, such as injections (for prevention of drug-induced neurotoxicity as discussed previously), eye drops (for glaucoma treatment) [56], dermal preparations [63] and oral formulations. GSH supplements may potentially provide a therapeutic strategy for diseases caused by abnormalities in tissue ROS levels. ...
Glutathione (GSH) is a tripeptide with potent antioxidant activity, which is involved in numerous basic biological processes and has been used for interventions in various degenerative diseases. However, oral delivery of GSH remains challenging, similarly to that of other protein and peptide drugs, because the physicochemical barriers in the gastrointestinal (GI) tract lead to low oral bioavailability. Although several approaches have been explored to improve delivery, such as co-administration with penetration enhancers and enzymatic inhibitors, or encapsulation into nanoparticles, microemulsions and liposomes, appropriate formulations with clinical therapeutic effects remain to be developed. This review discusses approaches explored to developing an oral GSH delivery system that could provide protection against proteolytic degradation in the GI tract and enhance molecular absorption across the epithelial membrane. This system may be beneficial for the design and development of an oral formulation of GSH in the future.
... Glutathione is an important component to maintain intracellular redox balance and regulates cell melanin production through various mechanisms, so its skin lightening effect was expected [107]. The results of clinical trials on the skin lightening effect and safety of glutathione reported so far are not fully consistent or conclusive [108,109]. ...
Melanin pigment is a major factor in determining the color of the skin, and its abnormal increase or decrease can cause serious pigmentation disorders. The melanin pigment of the skin is divided into light pheomelanin and dark eumelanin, and a big difference between them is whether they contain sulfur. Melanin synthesis starts from a common reaction in which tyrosine or dihydroxyphenylalanine (DOPA) is oxidized by tyrosinase (TYR) to produce dopaquinone (DQ). DQ is spontaneously converted to leukodopachrome and then oxidized to dopachrome, which enters the eumelanin synthesis pathway. When DQ reacts with cysteine, cysteinyl dopa is generated, which is oxidized to cysteinyl DQ and enters the pheomelanin synthesis pathway. Therefore, thiol compounds can influence the relative synthesis of eumelanin and pheomelanin. In addition, thiol compounds can inhibit enzymatic activity by binding to copper ions at the active site of TYR, and act as an antioxidant scavenging reactive oxygen species and free radicals or as a modulator of redox balance, thereby inhibiting overall melanin synthesis. This review will cover the metabolic aspects of thiol compounds, the role of thiol compounds in melanin synthesis, comparison of the antimelanogenic effects of various thiol compounds, and clinical trials on the skin lightening efficacy of thiol compounds. We hope that this review will help identify the advantages and disadvantages of various thiol compounds as modulators of skin pigmentation and contribute to the development of safer and more effective strategies for the treatment of pigmentation disorders.
... These include its inhibitory effect on tyrosinase enzyme, its ability to modify the melanogenesis process from the darker eumelanin to the lighter phaeomelanin, and its strong free radical scavenging properties [179]. Due to limited absorption and bioavailability of glutathione in oral form [180], topical application strategies have expanded, notably the use of topical GSSG for skin whitening and improving skin conditions and that of a GSH-loaded dissolving microneedle patch prepared with hyaluronic acid [181,182], to improve skin permeability, while reducing the unpleasant odor of GSH. ...
Reactive oxygen species (ROS) are necessary for normal cell signaling and the antimicrobial defense of the skin. However excess production of ROS can disrupt the cellular redox balance and overwhelm the cellular antioxidant (AO) capacity, leading to oxidative stress. In the skin, oxidative stress plays a key role in driving both extrinsic and intrinsic aging. Sunlight exposure has also been a major contributor to extrinsic photoaging of the skin as its oxidising components disrupt both redox- and iron-homeostasis, promoting oxidative damage to skin cells and tissue constituents. Upon oxidative insults, the interplay between excess accumulation of ROS and redox-active labile iron (LI) and its detrimental consequences to the skin are often overlooked. In this review we have revisited the oxidative mechanisms underlying skin damage and aging by focussing on the concerted action of ROS and redox-active LI in the initiation and progression of intrinsic and extrinsic skin aging processes. Based on these, we propose to redefine the selection criteria for skin antiaging and photoprotective ingredients to include natural antioxidants (AOs) exhibiting robust redox–balancing and/or iron-chelating properties. This would promote the concept of natural-based or bio-inspired bifunctional anti-aging and photoprotective ingredients for skincare and sunscreen formulations with both AO and iron-chelating properties.
... A recent review dealing with the clinical effect of glutathione on skin color has been published after the completion of our trial. 34 This article concluded that more quality studies were necessary before being able to be totally affirmative about the existence of the skin-lightening activity of glutathione although there was a marked trend that it can brighten skin color. Interestingly, this review concluded that only a daily dose of 500 mg of Glutathione was able to significantly induce a lightening of the sun-exposed skin, whereas 250 mg per day was ineffective. ...
Background
Glutathione has become a potential skin‐lightening ingredient after the discovery of its anti‐melanogenic properties. Various mechanisms of action have been considered to explain this property, one of them being the skewing of the melanin synthesis pathway towards the production of lighter pheomelanin instead of darker eumelanin, consequently producing a lightening effect.
Aims
To evaluate the skin lightening and anti‐dark spot effects of oral supplementation with L‐Cystine associated with L‐Glutathione as compared to placebo and benchmark.
Methods
Effects of this L‐Cystine‐L‐Glutathione oral combination were investigated in a 12‐week randomized, double‐blind, parallel‐group, benchmark‐ and placebo‐controlled trial involving 124 Asian female subjects. Women were randomly allocated into 4 equal groups (500 mg L‐Cystine and 250 mg L‐Glutathione, 250 mg reduced L‐Glutathione, 500 mg L‐Cystine, or a placebo, daily). Skin color was measured at baseline, after 6 and 12 weeks by spectrophotometry. Size and color of facial dark spots were determined from digital photographs.
Results
A significant skin lightening was observed after 12 weeks of oral supplementation with L‐Cystine associated with L‐Glutathione. This combination also induced a significant reduction in the size of facial dark spots after 6 and 12 weeks. It is noteworthy that the observed effects were not only significantly better than those obtained with placebo, but also with L‐Cystine alone or L‐Glutathione alone.
Conclusion
The daily oral administration of 500 mg L‐Cystine and 250 mg L‐Glutathione during 12 weeks was a safe treatment to effectively lighten the skin and reduce the size of facial dark spots of Asian women.
... 13 Oral glutathione has a low bioavailability, and this may be the motive behind the pursuit of intravenous (IV) glutathione. 27 The estimated half-life of oral glutathione in plasma is 1.6 min. 39 Additionally, it should be noted that any skin lightening treatments sought from this method are temporary as pheomelanin production is low and inconsistent. ...
The skin bleaching industry is a global business with a vast array of anti-melanogenic choices including glutathione. Glutathione is synthesized in vivo but has been used as a bodily supplement by medical personnel to aid in preventative medicine. Known for its antioxidant properties, glutathione has been used for its anti-melanogenic effects. Intravenous glutathione requires more investigation to determine its safety for usage. It continues to be distributed to the cosmetic industry despite antagonism from the Philippine FDA. This study will research the potential effects of intravenous glutathione on women and it will propose the biochemical mechanisms of glutathione in induced disease states in women. The aim is to educate people about safer methods for skin lightening.
Keywords: skin lightening, intravenous glutathione, pheomelanin, Fitzpatrick skin types, Stevens-Johnson syndrome.
... A systematic review performed by Dulokthornsakul et al. also stated there was a trend that glutathione might lighten skin color at sun-exposed areas. However, its skin-whitening effect was still inconclusive, with its inconsistent findings from several studies [13]. e limitations of oral clinical trials are evident since the ability of GSH as an intact molecule decreases as it passes through the gastrointestinal tract. ...
Objectives:
To compare the efficacy and safety profiles of systemic glutathione as a skin-whitening agent in adults from several randomized controlled trials (RCTs).
Methods:
This study is an evidence-based case report with literature search conducted on Clinical Key, Cochrane, Journal of the American Academy of Dermatology, Taylor and Francis Online, ScienceDirect, and PubMed databases. Three relevant RCTs were extracted and assessed for validity, importance, and applicability.
Results:
From 3 included trials, one of the studies opposed glutathione as a skin-whitening agent. However, the other two showed significant results only to some parts of the body or to certain age groups. As a skin-whitening agent, studies showed that glutathione yielded other cosmetic benefits as it may improve skin elasticity and reduce skin wrinkles. Furthermore, glutathione was well tolerated in oral preparations, but not in parenteral preparations.
Conclusions:
Highest-evidence literatures showed that glutathione is not beneficial enough as a skin-whitening agent as it was only effective in some parts of the body and did not elicit long-lasting effects. However, its safety profiles in oral preparations were well tolerated. More researches regarding the time needed for skin color to return to its original state following drug withdrawal need to be conducted as it is yet to be discovered.
... IV use of GSH has been associated with severe lifethreatening reactions including Stevens-Johnson syndrome and anaphylaxis [41]. According to Dilokthornsakul et.al, 2019 skin whitening effect of glutathione is still inconclusive due to the quality of included studies and inconsistent findings [63]. Cosmetic doctors have called on the UK government to warn consumers about the dangers of skin whitening antioxidant glutathione. ...
Hyperpigmentation is one of the most common skin disorders that affects both men and women of all ethnic groups, caused by several factors, such as UV exposure and skin inflammation. Topical whitening agents were found to be the best and the least aggressive therapy for treating hyperpigmentation compared to instrumental approaches. However, topical treatment faces several obstacles due to the low stability of the whitening agents. The number of patients that visit dermatologists with pigmentary disorders is significant. Patients are often overwhelmed with numerous OTC skin lightening agents, many without clinical evidence of efficacy. However, evidence-based studies on many of these agents are still lacking. The treatment of melasma should include a multimodality approach that incorporates photoprotective agents, antioxidant treatments, skin lighteners, exfoliants, and resurfacing procedures, as needed. Evidence-based studies suggest that first line therapies for melasma encompass intense photoprotection and topical lightening agents. Second-line treatments, such as chemical peels and lasers, are efficacious in some patients, but these approaches can be associated with acute and long-term complications, particularly in individuals with darker skin types. Given the global negative impact of melasma on the quality of life, a quest to find more efficacious treatments that offer sustained long-term remission for patients with this frustrating and therapeutically challenging disorder is ongoing.
[Purpose] This review aimed to investigate the effects of vitamin C and glutathione supplementation on exercise performance.[Methods] We conducted a literature search across the PubMed, Google Scholar, and Web of Science databases using the keywords vitamin C, glutathione, antioxidants, exercise, and oxidative stress.[Results] The effects of vitamin C supplementation on exercise performance and oxidative stress levels are inconsistent. Glutathione, with its diverse forms of supplementation and methods, presents mixed outcomes. Vitamin C and glutathione have deeply interconnected antioxidant functions and are mutualy essential to each other. Research investigating the combined intake of these two substances, which are intricately linked biochemically, and their effects on exercise performance remain largely unexplored.[Conclusion] Studies on the effects of vitamin C and glutathione intake on exercise have been conducted using diverse approaches; however, the results have not been consistent. Although an additive effect is anticipated with the combined intake of vitamin C and glutathione, research on this topic is currently insufficient, and further studies are required.
Immune-mediated skin diseases have a high prevalence and seriously affect patients’ quality of life. Gold compounds have been considered promising therapeutic agents in dermatology, but the high incidence of adverse reactions have limited their clinical application. There is a great need to develop more effective and less toxic gold-based drugs. Gold nanoclusters fabricated by using peptides (pep-AuNCs) have appeared as potential biomedical nanomaterials because of their excellent biocompatibility, ease of fabrication and unique physicochemical properties. Glutathione (GSH) is an endogenous tripeptide and has been used for lightening the skin color. Therefore, we fabricated a well-defined gold nanocluster with GSH as an example to explore the immunomodulatory effect of AuNCs on a TNF-α-treated human keratinocyte cell line (HaCaT) in vitro, the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced irritant contact dermatitis (ICD) model and the oxazolone (OXA)-induced psoriatic model in vivo. The results indicated that topically applied AuNCs successfully attenuated the severity of ICD and psoriasis-like lesions. In vitro and in vivo, AuNCs effectively inhibited the abnormal activation of the NF-κB pathway and the consequent overexpression of proinflammatory cytokines in keratinocytes. In particular, the transactivation of IL-17A, the most important cytokine in psoriasis pathology, was effectively inhibited by AuNCs treatment. In addition, AuNCs did not show any obvious cytotoxicity in HaCaT cells at doses even up to 100 µM and did not induce any irritation in the healthy skin and major organs, which indicated their favorable biosafety. These results indicate that biocompatible pep-AuNCs might be a promising gold-based nanomedicine for the treatment of inflammatory skin diseases.
Gamma-glutamyl-cysteine (γ-EC) is a precursor of glutathione (GSH) biosynthesis. We investigated whether it functions as a substrate for three intracellular and one extracellular GSH metabolic enzymes, which mediate the antioxidant defense function of GSH. Among them, glutathione peroxidase, glutathione S-transferase, and γ-glutamyl transferase (GGT) exhibited substrate specificity for γ-EC, whereas glutathione reductase did not. The specificities of γ-EC and its disulfide form to GGT were comparable to GSH and its oxidized form, GSSG, respectively. These result indicate that they can supply GSH constituent amino acids, glutamate, cysteine, and cystine through degradation by GGT. γ-EC may contribute valuable antioxidant defense properties as a food and cosmetic additive.
Skin is the outmost layer of human and sustains most of the external UVB irradiation, which is possibly cause the skin photoaging. As a natural antioxidant, marine natural products have been paid more and more attention to their positive effects on photoaging. 6,6’‐bieckol is a phlorotanin isolated from Ecklonia cava, while its anti‐photoaging bioactivity and mechanism have not been clear yet. This study proves that 6,6’‐bieckol enhances cells viability and decreases the level of ROS in UVB‐induced human immortalized keratinocytes (HaCaT) cells. It also resulted in significant down‐regulation of matrix metalloproteinases (MMPs), p‐c‐Fos, phosphorylated JNK, p38, IκB, and p65. In addition, molecular docking also showed that 6,6’‐bieckol could bind to MMP‐1, MMP‐3, and MMP‐9. Finally, it was proved that 6,6'‐bieckol acts on MMPs through the MAPK/AP‐1 and NF‐κB pathways to reduce UVB‐induced oxidative stress damage in HaCaT cells. Therefore, 6,6'‐bieckol is a functional food and skin care ingredient with great potential in preventing photoaging.
With globalization, cultural cosmetic practices with roots in South Asia, the Middle East, and Africa such as threading, henna, and skin lightening have become more prevalent throughout the world. Cultural competency and cultural humility in understanding these unique practices and traditions is increasingly important for dermatologists in both building a strong physician-patient relationship and identifying and treating cutaneous sequelae that may arise.
Background/objectives:
Glutathione (GSH) is the most abundant endogenous antioxidant and a critical regulator of oxidative stress. Maintenance of optimal tissues for GSH levels may be an important strategy for the prevention of oxidative stress-related diseases. We investigated if oral administration of liposomal GSH is effective at enhancing GSH levels in vivo.
Subjects/methods:
A 1-month pilot clinical study of oral liposomal GSH administration at two doses (500 and 1000 mg of GSH per day) was conducted in healthy adults. GSH levels in whole blood, erythrocytes, plasma and peripheral blood mononuclear cells (PBMCs) were assessed in 12 subjects at the baseline and after 1, 2 and 4 weeks of GSH administration.
Results:
GSH levels were elevated after 1 week with maximum increases of 40% in whole blood, 25% in erythrocytes, 28% in plasma and 100% in PBMCs occurring after 2 weeks (P<0.05). GSH increases were accompanied by reductions in oxidative stress biomarkers, including decreases of 35% in plasma 8-isoprostane and 20% in oxidized:reduced GSH ratios (P<0.05). Enhancements in immune function markers were observed with liposomal GSH administration including Natural killer (NK) cell cytotoxicity, which was elevated by up to 400% by 2 weeks (P<0.05), and lymphocyte proliferation, which was elevated by up to 60% after 2 weeks (P<0.05). Overall, there were no differences observed between dose groups, but statistical power was limited due to the small sample size in this study.
Conclusions:
Collectively, these preliminary findings support the effectiveness of daily liposomal GSH administration at elevating stores of GSH and impacting the immune function and levels of oxidative stress.European Journal of Clinical Nutrition advance online publication, 30 August 2017; doi:10.1038/ejcn.2017.132.
Background
Previous studies showed that supplementation of reduced form of glutathione (GSH, 500 mg/d) has a skin-lightening efficacy in humans. This study was designed to evaluate the influences of both GSH and oxidized form (GSSG), at doses lower than 500 mg/d, on improving skin properties.
Patients and methods
A randomized, double-blind, placebo-controlled, parallel, three-arm study was conducted. Healthy female subjects were equally randomized into three groups and took GSH (250 mg/d), GSSG (250 mg/d), or placebo orally for 12 weeks. At each visit at baseline and for 12 weeks, skin features including melanin index, wrinkles, and other relevant biophysical properties were measured. Blood samples were collected for safety monitoring.
Results
In generalized estimating equation analyses, melanin index and ultraviolet spots of all sites including face and arm when given GSH and GSSG tended to be lower than placebo. At some sites evaluated, subjects who received GSH showed a significant reduction in wrinkles compared with those taking placebo. A tendency toward increased skin elasticity was observed in GSH and GSSG compared with placebo. There were no serious adverse effects throughout the study.
Conclusion
We showed that oral glutathione, 250 mg/d, in both reduced and oxidized forms effectively influences skin properties. Overall, glutathione in both forms are well tolerated.
Non-randomised studies of the effects of interventions are critical to many areas of healthcare evaluation, but their results may be biased. It is therefore important to understand and appraise their strengths and weaknesses. We developed ROBINS-I ("Risk Of Bias In Non-randomised Studies-of Interventions"), a new tool for evaluating risk of bias in estimates of the comparative effectiveness (harm or benefit) of interventions from studies that did not use randomisation to allocate units (individuals or clusters of individuals) to comparison groups. The tool will be particularly useful to those undertaking systematic reviews that include non-randomised studies.
Background:
Glutathione (GSH) is the most abundant naturally occurring non-protein thiol that protects mammalian cells from oxidative stress. Intravenous (IV) GSH for skin lightening is advertised by clinics in South Africa and internationally online, yet to date no published review on the subject exists. Methods. We conducted a MEDLINE search (to 30 September 2015) of GSH use for skin lightening and of all indications in medicine, to evaluate its safety. Results. Two controlled clinical trials (GSH capsules: 60 patients; 2% glutathione disulphide lotion: 30 patients) and a case series (GSH lozenges: 30 patients) reported a significantly decreased melanin index. A case series (GSH soap: 15 patients) reported skin lightening based on photography. Two systematic reviews of IV GSH for preventing chemo-induced toxicity and a third review of adjuvant therapy for Parkinson's disease altogether included 10 trials. Most trials reported either no or minimal GSH adverse effects, but all had treatment durations of a few doses (IV) or 4 -12 weeks. No study reported long-term IV GSH use. Conclusion. In spite of widespread reported use, there are no studies of IV GSH use for skin lightening or of its safety for chronic use (for any indication). The switch from brown to red melanin production may increase the risk of sun-induced skin cancers in previously protected individuals. Regulatory assessment of systemic GSH administration for cosmetic use by the Medicines Control Council seems urgently warranted to protect consumers from potential side-effects and from complications of IV infusions. This is especially concerning because of reports of GSH bought online. Effective topical GSH may be useful for hyperpigmented skin disorders, but this requires scientific scrutiny. The debate on the merits of cosmetic skin lightening is best handled by multidisciplinary teams.
Terrestrial solar ultraviolet radiation exerts both beneficial and adverse effects on human skin. Epidemiological studies show a lower incidence of skin cancer in people with pigmented skins compared to fair skins. This is attributed to photoprotection by epidermal melanin, as is the poorer vitamin D status of those with darker skins. We summarize a wide range of photobiological responses across different skin colours including DNA damage and immunosuppression. Some studies show the generally modest photoprotective properties of melanin, but others show little or no effect. DNA photodamage initiates non-melanoma skin cancer and is reduced by a factor of about 3 in pigmented skin compared with white skin. This suggests that if such a modest reduction in DNA damage can result in the significantly lower skin cancer incidence in black skin, the use of sunscreen protection might be extremely beneficial for susceptible population. Many contradictory results may be explained by protocol differences, including differences in UVR spectra and exposure protocols. We recommend that skin type comparisons be done with solar simulating radiation and physical doses (J/m2) rather than those based solely on clinical endpoints such as erythema. This article is protected by copyright. All rights reserved.
Glutathione is a low molecular weight thiol-tripeptide that plays a prominent role in maintaining intracellular redox balance. In addition to its remarkable antioxidant properties, the discovery of its antimelanogenic properties has led to its promotion as a skin-lightening agent. It is widely used for this indication in some ethnic populations. However, there is a dichotomy between evidence to support its efficacy and safety. The hype around its depigmentary properties may be a marketing gimmick of pharma-cosmeceutical companies. This review focuses on the various aspects of glutathione: its metabolism, mechanism of action and the scientific evidence to evaluate its efficacy as a systemic skin-lightening agent. Glutathione is present intracellularly in its reduced form and plays an important role in various physiological functions. Its skin-lightening effects result from direct as well as indirect inhibition of the tyrosinase enzyme and switching from eumelanin to phaeomelanin production. It is available in oral, parenteral and topical forms. Although the use of intravenous glutathione injections is popular, there is no evidence to prove its efficacy. In fact, the adverse effects caused by intravenous glutathione have led the Food and Drug Administration of Philippines to issue a public warning condemning its use for off-label indications such as skin lightening. Currently, there are three randomized controlled trials that support the skin-lightening effect and good safety profile of topical and oral glutathione. However, key questions such as the duration of treatment, longevity of skin-lightening effect and maintenance protocols remain unanswered. More randomized, double-blind, placebo-controlled trials with larger sample size, long-term follow-up and well-defined efficacy outcomes are warranted to establish the relevance of this molecule in disorders of hyperpigmentation and skin lightening.
Glutathione (GSH) is critical to fight against oxidative stress. Its very low bioavailability limits the interest of a supplementation. The purpose of this study was to compare the bioavailability, the effect on oxidative stress markers and the safety of a new sublingual form of GSH with two commonly used dietary supplements, N-acetylcysteine (NAC) and oral GSH. The study was a three-week randomized crossover trial. 20 Volunteers with metabolic syndrome were enrolled. GSH levels and several oxidative stress markers were determined at different times during each 21-days period. Compared to oral GSH group, an increase of total and reduced GSH levels in plasma and a higher GSH/GSSG ratio (p=0.003) was observed in sublingual GSH group. After 3 weeks of administration, there was a significant increase of vitamin E level in plasma only in sublingual GSH group (0.83µmol/g; p=0.04). Our results demonstrate the superiority of a new sublingual form of GSH over the oral GSH form and NAC in terms of GSH supplementation.
Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
Purpose
Glutathione is a tripeptide consisting of cysteine, glycine, and glutamate and functions as a major antioxidant. It is synthesized endogenously in humans. Glutathione protects thiol protein groups from oxidation and is involved in cellular detoxification for maintenance of the cell environment. Reduced glutathione (GSH) has a skin-whitening effect in humans through its tyrosinase inhibitory activity, but in the case of oxidized glutathione (GSSG) this effect is unclear. We examined the skin-whitening and skin-condition effects of topical GSSG in healthy women.
Subjects and methods
The subjects were 30 healthy adult women aged 30 to 50 years. The study design was a randomized, double-blind, matched-pair, placebo-controlled clinical trial. Subjects applied GSSG 2% (weight/weight [w/w]) lotion to one side of the face and a placebo lotion to the other side twice daily for 10 weeks. We objectively measured changes in melanin index values, moisture content of the stratum corneum, smoothness, wrinkle formation, and elasticity of the skin. The principal investigator and each subject also used subjective scores to investigate skin whitening, wrinkle reduction, and smoothness. Analysis of variance was used to evaluate differences between groups.
Results
The skin melanin index was significantly lower with GSSG treatment than with placebo from the early weeks after the start of the trial through to the end of the study period (at 10 weeks, P<0.001). In addition, in the latter half of the study period GSSG-treated sites had significant increases in moisture content of the stratum corneum, suppression of wrinkle formation, and improvement in skin smoothness. There were no marked adverse effects from GSSG application.
Conclusion
Topical GSSG is safe and effectively whitens the skin and improves skin condition in healthy women.
Being the largest and most visible organ of the body and heavily influenced by environmental factors, skin is ideal to study the long-term effects of aging. Throughout our lifetime, we accumulate damage generated by UV radiation. UV causes inflammation, immune changes, physical changes, impaired wound healing and DNA damage that promotes cellular senescence and carcinogenesis. Melanoma is the deadliest form of skin cancer and among the malignancies of highest increasing incidence over the last several decades. Melanoma incidence is directly related to age, with highest rates in individuals over the age of 55 years, making it a clear age-related disease. In this review, we will focus on UV-induced carcinogenesis and photo aging along with natural protective mechanisms that reduce amount of "realized" solar radiation dose and UV-induced injury. We will focus on the theoretical use of forskolin, a plant-derived pharmacologically active compound to protect the skin against UV injury and prevent aging symptoms by up-regulating melanin production. We will discuss its use as a topically-applied root-derived formulation of the Plectranthus barbatus (Coleus forskolii) plant that grows naturally in Asia and that has long been used in various Aryuvedic teas and therapeutic preparations.
Glutathione (GSH), the most abundant endogenous antioxidant, is a critical regulator of oxidative stress and immune function. While oral GSH has been shown to be bioavailable in laboratory animal models, its efficacy in humans has not been established. Our objective was to determine the long-term effectiveness of oral GSH supplementation on body stores of GSH in healthy adults.
A 6-month randomized, double-blinded, placebo-controlled trial of oral GSH (250 or 1,000 mg/day) on GSH levels in blood, erythrocytes, plasma, lymphocytes and exfoliated buccal mucosal cells was conducted in 54 non-smoking adults. Secondary outcomes on a subset of subjects included a battery of immune markers.
GSH levels in blood increased after 1, 3 and 6 months versus baseline at both doses. At 6 months, mean GSH levels increased 30-35 % in erythrocytes, plasma and lymphocytes and 260 % in buccal cells in the high-dose group (P < 0.05). GSH levels increased 17 and 29 % in blood and erythrocytes, respectively, in the low-dose group (P < 0.05). In most cases, the increases were dose and time dependent, and levels returned to baseline after a 1-month washout period. A reduction in oxidative stress in both GSH dose groups was indicated by decreases in the oxidized to reduced glutathione ratio in whole blood after 6 months. Natural killer cytotoxicity increased >twofold in the high-dose group versus placebo (P < 0.05) at 3 months.
These findings show, for the first time, that daily consumption of GSH supplements was effective at increasing body compartment stores of GSH.
Skin pigmentation is an important human phenotypic trait whose regulation, in spite of recent advances, has not yet been fully understood. The pigment melanin is produced in melanosomes by melanocytes in a complex process called melanogenesis. The melanocyte interacts with endocrine, immune, inflammatory and central nervous systems, and its activity is also regulated by extrinsic factors such as ultraviolet radiation and drugs. We have carried out a review of the current understanding of intrinsic and extrinsic factors regulating skin pigmentation, the melanogenesis stages and related gene defects. We focused on melanocyte-keratinocyte interaction, activation of melanocortin type 1 receptor (MC1-R) by peptides (melanocyte-stimulating hormone and adrenocorticotropic hormone) resulting from proopiomelanocortin (POMC) cleavage, and mechanisms of ultraviolet-induced skin pigmentation. The identification and comprehension of the melanogenesis mechanism facilitate the understanding of the pathogenesis of pigmentation disorders and the development of potential therapeutic options.
The tripeptide glutathione (GSH) is the most abundant free radical scavenger synthesized endogenously in humans. Increasing mechanistic, clinical, and epidemiological evidence demonstrates that GSH status is significant in acute and chronic diseases. Despite ease of delivery, little controlled clinical research data exist evaluating the effects of oral GSH supplementation.
The study objectives were to determine the effect of oral GSH supplementation on biomarkers of systemic oxidative stress in human volunteers.
This was a randomized, double-blind, placebo-controlled clinical trial.
The study was conducted at Bastyr University Research Institute, Kenmore, WA and the Bastyr Center for Natural Health, Seattle, WA.
Forty (40) adult volunteers without acute or chronic disease participated in this study. Intervention: Oral GSH supplementation (500 mg twice daily) was given to the volunteers for 4 weeks.
Primary outcome measures included change in creatinine-standardized, urinary F2-isoprostanes (F2-isoP) and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG). Changes in erythrocyte GSH concentrations, including total reduced glutathione (GSH), oxidized glutathione (GSSG), and their ratio (GSH:GSSG) were also measured by tandem liquid chromatography/mass spectrometry. Analysis of variance was used to evaluate differences between groups.
There were no differences in oxidative stress biomarkers between treatment groups at baseline. Thirty-nine (39) participants completed the study per protocol. Changes in creatinine standardized F2-isoP (ng/mg creatinine) (0.0±0.1 versus 0.0±0.1, p=0.38) and 8-OHdG (μg/g creatinine) (-0.2±3.3 versus 1.0±3.2, p=0.27) were nonsignificant between groups at week 4. Total reduced, oxidized, and ratio measures of GSH status were also unchanged.
No significant changes were observed in biomarkers of oxidative stress, including glutathione status, in this clinical trial of oral glutathione supplementation in healthy adults.
When the plasma glutathione concentration is low, such as in patients with HIV infection, alcoholics, and patients with cirrhosis, increasing the availability of circulating glutathione by oral administration might be of therapeutic benefit.
To assess the feasibility of supplementing oral glutathione we have determined the systemic availability of glutathione in 7 healthy volunteers.
The basal concentrations of glutathione, cysteine, and glutamate in plasma were 6.2, 8.3, and 54 μmol·l−1 respectively. During the 270 min after the administration of glutathione in a dose of 0.15 mmol·kg−1 the concentrations of glutathione, cysteine, and glutamate in plasma did not increase significantly, suggesting that the systemic availability of glutathione is negligible in man.
Because of hydrolysis of glutathione by intestinal and hepatic γ-glutamyltransferase, dietary glutathione is not a major determinant of circulating glutathione, and it is not possible to increase circulating glutathione to a clinically beneficial extent by the oral administration of a single dose of 3 g of glutathione.
Assessment of risk of bias is regarded as an essential component of a systematic review on the effects of an intervention. The most commonly used tool for randomised trials is the Cochrane risk-of-bias tool. We updated the tool to respond to developments in understanding how bias arises in randomised trials, and to address user feedback on and limitations of the original tool.
A consistent underlying index of aging is a decline in the cellular levels of the tripeptide glutathione (GSH). GSH is an essential thiol antioxidant produced in the cytosol of all cells and plays a key role in protecting against oxidative stress by neutralising free radicals and reactive oxygen species (ROS). The decline in GSH has been associated with changes in the expression and activity of the rate-limiting enzyme glutamate cysteine ligase (GCL), which produces the intermediate dipeptide γ-glutamylcysteine (γ-GC). The molecular mechanisms that affect these age-related changes remain unclear due to the complexity of GCL regulation. Impairment of the transcriptional activity of Nrf2 has been demonstrated to contribute to GCL dysregulation in aged rats. However, considering the complex nature of GCL regulation, relatively little research has been conducted to investigate the age-associated post-transcriptional controls of the enzyme. Defining these unknown mechanisms may inform our understanding of the aetiology of many age-related diseases and assist in formulating appropriate therapeutic strategies. This review focuses on the suitability of treatment with exogenous γ-GC to raise GSH levels by circumventing the age-related dysregulation of the rate-limiting step of GSH, providing promise for future research for the treatment of chronic oxidative stress-related diseases.
Glutathione (GSH) is a naturally occurring thiol that has been reported to cause skin lightening in a manner for which several mechanisms have been proposed. Highest plasma concentrations are achieved with IV administration but are accompanied by greater levels of risk. Oral administration has been less successful in elevating plasma GSH levels.
The use of a lozenge containing GSH was investigated in order to evaluate the buccal mucosa as a route for GSH administration. Substances that are absorbed through the buccal route go directly into the systemic circulation, effectively bypassing the gastrointestinal tract.
Thirty Filipino females with Fitzpatrick skin types IV or V received a glutathione-containing lozenge daily for eight weeks.
Findings showed a significant decrease in melanin indices from baseline to endpoint that became evident in as little as two weeks. There were no serious adverse events, and laboratory examination findings remained normal.
The authors conclude that the lozenge containing glutathione was safe and effective in lightening the skin of Filipino women.
© 2015 The International Society of Dermatology.
Evidence for the postulated role of glutathione reductase in melanin pigmentation has been obtained by determinations of the glutathione concentrations in Tortoiseshell guinea pig skin of different colors (black, yellow, red, and white). As expected, the lowest levels of reduced glutathione (GSH) were found associated with eumelanin type pigmentation, whereas the highest ones were found in the skin with phaeomelanin producing melanocytes. On the other hand, white skin of guinea pig having no active melanocytes showed GSH levels which were intermediate between those of the black and yellow areas.
These results are consistent with the view that the activity of the enzyme glutathione reductase, though not primarily related to pigmentation, plays an important role in the regulation and control of the biosynthetic activity of melanocytes leading to various types of melanin pigments.
Glutathione (GSH) is the most abundant antioxidant in aerobic cells, present in micromolar (microM)-concentrations in bodily fluids and in millimolar (mM) concentrations in tissue. GSH is critical for protecting the brain from oxidative stress, acting as a free radical scavenger and inhibitor of lipid peroxidation. GSH also participates in the detoxification of hydrogen peroxide by various glutathione peroxidases. The ratio of reduced GSH to oxidized GSH (GSSG) is an indicator of cellular health, with reduced GSH constituting up to 98% of cellular GSH under normal conditions. However, the GSH/GSSG ratio is reduced in neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease (AD). Measuring the GSH/GSSG ratio in pathological tissues and experimental models thereof in comparison to the results in controls is an excellent way to assess potential therapeutics efficacy in maintaining cellular redox potential. The availability of UV/Visible instruments equipped with 96-well plate readers as common laboratory equipment has made measuring the GSH/GSSG ratio on multiple samples a manageable procedure.
To determine whether orally administered glutathione, 500 mg per day for 4 weeks, affects the skin melanin index, when compared with placebo.
This randomized, double-blind, two-arm, placebo-controlled study was set in the King Chulalongkorn Memorial Hospital, Bangkok, Thailand, a teaching hospital affiliated with a medical school. Sixty otherwise healthy medical students were randomized to receive either glutathione capsules, 500 mg/day in two divided doses, or placebo for 4 weeks. The main outcome was mean reduction of melanin indices measured at six different sites. Several secondary outcomes, including UV spots, were recorded by VISIA™. Efficacies of glutathione and placebo were compared by ANCOVA with baseline values as co-variates.
Sixty participants enrolled and completed the study. At 4 weeks, the melanin indices decreased consistently at all six sites in subjects who received glutathione. The reductions were statistically significantly greater than those receiving placebo at two sites, namely the right side of the face and the sun-exposed left forearm (p-values = 0.021 and 0.036, respectively). This was similarly reflected in the changes in the number of UV spots, as measured by VISIA. Both glutathione and placebo were very well tolerated.
Oral glutathione administration results in a lightening of skin color in a small number of subjects. However, long-term safety has not been established and warrants more extensive clinical trials.
This review is the introduction to a special issue concerning, glutathione (GSH), the most abundant low molecular weight thiol compound synthesized in cells. GSH plays critical roles in protecting cells from oxidative damage and the toxicity of xenobiotic electrophiles, and maintaining redox homeostasis. Here, the functions and GSH and the sources of oxidants and electrophiles, the elimination of oxidants by reduction and electrophiles by conjugation with GSH are briefly described. Methods of assessing GSH status in the cells are also described. GSH synthesis and its regulation are addressed along with therapeutic approaches for manipulating GSH content that have been proposed. The purpose here is to provide a brief overview of some of the important aspects of glutathione metabolism as part of this special issue that will provide a more comprehensive review of the state of knowledge regarding this essential molecule.
Glutathione is an ubiquitous compound found in our bodies. Aside from its many ascribed biologic functions, it has also been implicated in skin lightening. We review in vitro and in vivo studies that show evidence of its involvement in the melanogenic pathway and shed light on the its anti-melanogenic effect. Proposed mechanisms of action include: (a) direct inactivation of the enzyme tyrosinase by binding with the copper-containing active site of the enzyme; (b) mediating the switch mechanism from eumelanin to phaeomelanin production; (c) quenching of free radicals and peroxides that contribute to tyrosinase activation and melanin formation; and d) modulation of depigmenting abilities of melanocytotoxic agents. These concepts supported by the various experimental evidence presented form basis for future research in the use of glutathione in the treatment of pigmentary disorders.
Le glutathion est un composé ubiquitaire présent dans nos organismes. En plus de ses fonctions biologiques déjà décrites, il a été impliqué dans le blanchissement de la peau. Nous passons en revue les études in vitro et in vivo qui apportent des preuves de son implication dans la voie de la mélanogénèse et des possibles explications de son effet anti mélanogénétique. Les mécanismes proposés de cette action incluent: (a) une inactivation directe de l'enzyme tyrosinase par liaison au Cuivre du site actif de l'enzyme; (b) influencer le mécanisme de bascule entre la production d'eumélanine vers la phaeomélanine; (c) extinction des radicaux libres et des peroxydes qui contribuent à activer la tyrosinase; et (d) modulation des capacités dépigmentantes des agents mélanocytotoxiques. Les concepts appuyés par les diverses démonstrations expérimentales présentées ici forment les bases des recherches futures sur l'utilisation du glutathion dans le traitement des désordres pigmentaires.
Sirona Biochem: Potential home run with big licensing deal in Q4
- Media Comcap
Media ComCap. Sirona Biochem: Potential home run with big licensing deal in Q4/2016. In: Sirona Biochem: Potential home run
with big licensing deal in Q4/2016, Vol. 2017, 2016.