The Role of Vitamin E in Thermal Burn Injuries, Infection, and Sepsis: A Review

Marc A Thompson, Kameel Zuniga, Linda Sousse, Robert Christy, Jennifer Gurney

J Burn Care Res . 2022 Jul 21;irac100. doi: 10.1093/jbcr/irac100. Online ahead of print

Abstract

Thermal burn injuries are still a serious public health concern in the United States, due to the initial insult and resulting co-morbidities. Burned patients are increasingly susceptible to colonization by endogenous and exogenous micro-organisms after having lost skin, which acts as the primary protective barrier to environmental contaminants. Furthermore, the onset of additional pathophysiologies, specifically sepsis, becomes more likely in burned patients compared to other injuries. Despite improvements in the early care of burn patients, infections, and sepsis, these pathophysiologies remain major causes of morbidity and mortality and warrant further investigation of potential therapies. Vitamin E may be one such therapy. We aimed to identify publications of studies that evaluated the effectiveness of vitamin E as it pertains to thermal burn injuries, infection, and sepsis. Several investigations ranging from in vitro bench work to clinical studies have examined the impact on, or influence of, vitamin E in vitro, in vivo, and in the clinical setting. To the benefit of subjects it has been shown that enteral or parenteral vitamin E supplementation can prevent, mitigate, and even reverse the effects of thermal burn injuries, infection, and sepsis. Therefore, a large scale prospective observational study to assess the potential benefits of vitamin E supplementation in patients is warranted and could result in clinical care practice paradigm changes.

Wai Ting Chong, Chin Ping Tan, Yoke Kqueen Cheah, Oi Ming Lai

PLoS One . 2022 May 25;17(5):e0267381. doi: 10.1371/journal.pone.0267381. eCollection 2022

Abstract

Proper wound healing is vital for the survival of higher organisms. Responses to skin injury can lead to complications such as scar formation that can affect the quality of life. In this study, keratinocytes migration (scratch assay) and zebrafish tail regeneration experiments were used to evaluate the wound healing effect of a tocotrienol-based nanoemulsified (NE) system against ascorbic acid and phosphate-buffered saline (PBS) as positive and negative controls, respectively. MTT assay provided a concentration range of 0.35-8.75 μg/ml of nanoemulsion that produced cell viability more than 100%. After 24 hours of treatment, the wound closure of keratinocytes were found to be significantly faster by 73.76%, 63.37% and 35.56%, respectively when treated with 3.50 μg/ml and 1.75 μg/ml of NE compared to the blank. The lethal concentration at 50% (LC50 value) obtained from acute and prolonged toxicity was almost similar, which was 4.6 mg/ml and 5.0 mg/ml, respectively. Growth of zebrafish tail regeneration treated with NE at a concentration of 2.5 mg/ml was significantly faster than the untreated zebrafish, which regenerated to 40% on the fifth day, more than 60% on the tenth day of treatment and fully recovered at the twentieth day. In conclusion, these results showed the potential of the tocotrienols-based nanoemulsified system in enhancing wound healing through accelerated wound closure.

Xiaofang Liu, Guang Yang, Mengxin Luo, Qi Lan, Xiaoxia Shi, Haoyuan Deng, Ningning Wang, Xuezhu Xu, Cong Zhang

PLoS One . 2021 Dec 14;16(12):e0261259. doi: 10.1371/journal.pone.0261259. eCollection 2021.

Abstract

Background: Vitamin E has long been linked to skin health, including all of its possible functions in cosmetic products, to its roles in membrane integrity and even the aging process. However, reports on the relationship between serum vitamin E levels and the risk of chronic inflammatory skin diseases have been inconsistent. We performed a systematic review and meta-analysis to evaluate the association between serum vitamin E levels and chronic inflammatory skin diseases.

Methods: We searched the PubMed, Web of Science and Scopus databases, with no time limit up to 30.06.2021. Studies examining serum vitamin E levels in patients with chronic inflammatory skin diseases were selected.

Results: Twenty articles met the inclusion criteria. Compared with controls, a lower vitamin E level was found in patients with vitiligo (SMD: -0.70, 95% CI: -1.21 to -0.19), psoriasis (SMD: -2.73, 95% CI: -3.57 to -1.18), atopic dermatitis (SMD: -1.08, 95% CI: -1.80 to -0.36) and acne (SMD: -0.67, 95% CI: -1.05 to -0.30).

Conclusions: Our meta-analysis showed that serum vitamin E levels were lower in patients suffering from vitiligo, psoriasis, atopic dermatitis and acne. This study highlights the need to evaluate vitamin E status to improve its level in patients with skin diseases.

Erin M Warshaw, Jenna L Ruggiero, Joel G DeKoven, Jonathan I Silverberg, Howard I Maibach, James S Taylor, Amber R Atwater, Kathryn A Zug, Denis Sasseville, Joseph F Fowler Jr, Anthony F Fransway, Melanie D Pratt, Donald V Belsito, Vincent A DeLeo, Margo J Reeder

Dermatitis . 2021 Sep-Oct 01;32(5):308-318. doi: 10.1097/DER.0000000000000706.

Abstract

Background: Vitamin E (tocopherol) a naturally occurring mixture of antioxidants commonly used in topical skin care products, may cause allergic contact dermatitis.

Objective: The aim of this study was to characterize positive patch test reactions to tocopherol and tocopherol acetate.

Methods: This is a retrospective analysis of North American Contact Dermatitis Group patch test data to tocopherols (dl-α-tocopherol 100% and/or dl-α-tocopherol acetate 100%) from 2001 to 2016.

Results: Of the 38,699 patients patch tested to tocopherol and/or tocopherol acetate, 349 (0.9%) had positive reactions; of these, 87.6% were currently relevant. Most (51.4%) were weak (+) and/or not related to occupation (99.1%). Compared with tocopherol-negative patients, tocopherol-positive individuals were more likely to be female (72.5% vs 67.2%, P = 0.0355), have a final primary diagnosis of allergic contact dermatitis (74.2% vs 52.6%, P < 0.0001), and have dermatitis in a scattered generalized distribution (23.8% vs 18.2%, P = 0.0072); they were also less likely to have hand involvement (16.6% vs 22.3%, P = 0.0064). The most common source of tocopherol was personal care products, especially moisturizers.

Conclusions: Positive patch test reactions to tocopherols were relatively rare given their widespread use. When positive, current clinical relevance was high. Tocopherol-positive patients were more likely to be female and presented with dermatitis on the face or in a scattered generalized pattern.

Enzo Berardesca, Norma Cameli

Dermatol Ther . 2021 Oct 16;e15160. doi: 10.1111/dth.15160. Online ahead of print.

Abstract

Vitamin E is a powerful lipophilic antioxidant that protects membranes from lipid peroxidation, and consequently, oxidative damage. Oxidative stress plays a role in the development of neurodegenerative diseases. Vitamin E supplementation is recommended in patients with vitamin E deficiency due to fat malabsorption. The addition of vitamin E to the diet slows Alzheimer’s disease progression and protects older patients against respiratory infections. Recent studies also point to the involvement of oxidative stress in the pathology of immune-mediated skin diseases, such as atopic dermatitis and psoriasis. We reviewed the available clinical trials that investigated the role of vitamin E supplementation in preventing and treating atopic dermatitis and psoriasis. Data from these studies point to a positive role of vitamin E supplementation in these diseases. Still, due to limitations in study design, further evidence is needed to reach a definite conclusion.

Sooji Song, Yoon-Mi Lee, Yu Young Lee, Kyung-Jin Yeum

Molecules . 2021 Sep 13;26(18):5564. doi: 10.3390/molecules26185564.

Abstract

Oat (Avena sativa) is well known for its various health benefits. The protective effect of oat extract against oxidative stress-induced apoptosis in human keratinocytes HaCaT was determined. First, extracts of two varieties of oat, Daeyang and Choyang, were analyzed for fat-soluble antioxidants such as α-tocotrienol, γ-oryzanols, lutein and zeaxanthin using an UPLC system and for antioxidant activity using a DPPH assay. Specifically, an 80% ethanol extract of Daeyang oat (Avena sativa cv. Daeyang), which had high amounts of antioxidants and potent radical scavenging activity, was further evaluated for protective effect against oxidative stress-induced cell death, intracellular reactive oxygen species levels, the phosphorylation of DNA damage mediating genes such as H2AX, checkpoint kinase 1 and 2, and p53 and the activation of apoptotic genes such as cleaved caspase-3 and 7 and poly (ADP-ribose) polymerase in HaCaT cells. The Daeyang and Choyang oat 80% ethanol extracts had 26.9 and 24.1 mg/100 g γ-oryzanols, 7.69 and 8.38 mg/100 g α-tocotrienol, 1.25 and 0.34 mg/100 g of lutein and 1.20 and 0.17 mg/100 g of zeaxanthin, respectively. The oat 80% ethanol extract treatment (Avena sativa cv. Daeyang) had a protective effect on oxidative stress-induced cell death in HaCaT cells. In addition, the oat 80% ethanol extracts led to a significant decrease in the intracellular ROS level at a concentration of 50-200 μg/mL, the attenuation of DNA damage mediating genes and the inhibition of apoptotic caspase activities in a dose dependent manner (50-200 μg/mL). Thus, the current study indicates that an oat (Avena sativa cv. Daeyang) extract rich in antioxidants, such as polyphenols, avenanthramides, γ-oryzanols, tocotrienols and carotenoids, has a protective role against oxidative stress-induced keratinocyte injuries and that oat may a useful source for oxidative stress-associated skin damage.

Chee Chin Chu, Zafarizal Aldrin Bin Azizul Hasan, Chin Ping Tan, Kar Lin Nyam

J Pharm Sci . 2021 Aug 20;S0022-3549(21)00423-8. doi: 10.1016/j.xphs.2021.08.020.

Abstract

Chronic exposure to ultraviolet (UV) radiation leads to photoaging. There is a tremendous rise in products having a dual activity of photoprotection and antiaging. In vitro analysis in dermal fibroblasts and their biological mechanisms involved are critical to determine antiaging potential. The study aimed to investigate the antiaging potential of sunscreen formulated from nanostructured lipid carrier and tocotrienol-rich fraction (NLC-TRF sunscreen). The antioxidant activity of the NLC-TRF sunscreen was evaluated by radical scavenging and hydrogen peroxide inhibition properties. Also, collagenase, elastase and matrix metalloproteinase-1 (MMP-1) inhibition activities, and type I collagen and elastin protein expression were studied. Quantitative real-time polymerase chain reaction (qPCR) was used to evaluate the mRNA expression of fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), type I collagen (COL1A1), elastin (ELN), MMP-1, MMP-2, and tissue inhibitor matrix metalloproteinase-1 (TIMP-1). The results suggested that NLC-TRF sunscreen is effective in radical, anti-hydrogen peroxide, and collagenase, elastase and MMP-1 inhibition activities. Besides, a significant increase for type I collagen (3.47-fold) and elastin (2.16-fold) protein and fibroblast regeneration genes (FGF (2.12-fold), VEGF (1.91-fold), TGF-β1 (2.84-fold), TIMP-1 (1.42-fold), ELN (2.13-fold)) were observed after sample treatment. These findings support the therapeutic potential of NLC-TRF sunscreen in antiaging.

Katalin Koczok, László Horváth, Zeljka Korade, Zoltán András Mezei, Gabriella P Szabó, Ned A Porter, Eszter Kovács, Károly Mirnics, István Balogh

Biomolecules . 2021 Aug 17;11(8):1228. doi: 10.3390/biom11081228.

Abstract

Smith-Lemli-Opitz syndrome (SLOS) is a severe monogenic disorder resulting in low cholesterol and high 7-dehydrocholesterol (7-DHC) levels. 7-DHC-derived oxysterols likely contribute to disease pathophysiology, and thus antioxidant treatment might be beneficial because of high oxidative stress. In a three-year prospective study, we investigated the effects of vitamin E supplementation in six SLOS patients already receiving dietary cholesterol treatment. Plasma vitamin A and E concentrations were determined by the high-performance liquid chromatography (HPLC) method. At baseline, plasma 7-DHC, 8-dehydrocholesterol (8-DHC) and cholesterol levels were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The clinical effect of the supplementation was assessed by performing structured parental interviews. At baseline, patients were characterized by low or low-normal plasma vitamin E concentrations (7.19-15.68 μmol/L), while vitamin A concentrations were found to be normal or high (1.26-2.68 μmol/L). Vitamin E supplementation resulted in correction or significant elevation of plasma vitamin E concentration in all patients. We observed reduced aggression, self-injury, irritability, hyperactivity, attention deficit, repetitive behavior, sleep disturbance, skin photosensitivity and/or eczema in 3/6 patients, with notable individual variability. Clinical response to therapy was associated with a low baseline 7-DHC + 8-DHC/cholesterol ratio (0.2-0.4). We suggest that determination of vitamin E status is important in SLOS patients. Supplementation of vitamin E should be considered and might be beneficial.

Jessica Hoff, Berit Karl, Jana Gerstmeier, Uwe Beekmann, Lisa Schmölz, Friedemann Börner, Dana Kralisch, Michael Bauer, Oliver Werz, Dagmar Fischer, Stefan Lorkowski, Adrian T Press

Nanomaterials (Basel) . 2021 Jul 28;11(8):1939. doi: 10.3390/nano11081939.

Abstract

Inflammation is a hallmark of tissue remodeling during wound healing. The inflammatory response to wounds is tightly controlled and well-coordinated; dysregulation compromises wound healing and causes persistent inflammation. Topical application of natural anti-inflammatory products may improve wound healing, in particular under chronic pathological conditions. The long-chain metabolites of vitamin E (LCM) are bioactive molecules that mediate cellular effects via oxidative stress signaling as well as anti-inflammatory pathways. However, the effect of LCM on wound healing has not been investigated. We administered the α-tocopherol-derived LCMs α-13′-hydroxychromanol (α-13′-OH) and α-13′-carboxychromanol (α-13′-COOH) as well as the natural product garcinoic acid, a δ-tocotrienol derivative, in different pharmaceutical formulations directly to wounds using a splinted wound mouse model to investigate their effects on the wounds’ proinflammatory microenvironment and wound healing. Garcinoic acid and, in particular, α-13′-COOH accelerated wound healing and quality of the newly formed tissue. We next loaded bacterial nanocellulose (BNC), a valuable nanomaterial used as a wound dressing with high potential for drug delivery, with α-13′-COOH. The controlled release of α-13′-COOH using BNC promoted wound healing and wound closure, mainly when a diabetic condition was induced before the injury. This study highlights the potential of α-13′-COOH combined with BNC as a potential active wound dressing for the advanced therapy of skin injuries.

Lara Camillo, Elena Grossini, Serena Farruggio, Patrizia Marotta, Laura Cristina Gironi, Elisa Zavattaro, Paola Savoia

Skin Pharmacol Physiol . 2021 Jul 8;1-12. doi: 10.1159/000517204. Online ahead of print.

Abstract

Background: The altered balance between oxidants/antioxidants and inflammation, changes in nitric oxide (NO) release, and mitochondrial function have a role in skin aging through fibroblast modulation. Tocopherol is promising in counteracting the abovementioned events, but the effective mechanism of action needs to be clarified.

Objective: The aim of this study was to examine the effects of α-tocopherol on cell viability/proliferation, NO release, mitochondrial function, oxidants/antioxidants, and inflammation in human dermal fibroblasts (HDF) subjected to oxidative stress.

Methods: HDF were treated with H2O2 in the presence or absence of 1-10 μM α-tocopherol. Cell viability, reactive oxygen species (ROS), NO release, and mitochondrial membrane potential were measured; glutathione (GSH), superoxide dismutase (SOD)-1 and -2, glutathione peroxidase-1 (GPX-1), inducible NO synthase (iNOS), and Ki-67 were evaluated by RT-PCR and immunofluorescence; cell cycle was analyzed using FACS. Pro- and anti-inflammatory cytokine gene expression was analyzed through qRT-PCR.

Results: α-Tocopherol counteracts H2O2, although it remains unclear whether this effect is dose dependent. Improvement of cell viability, mitochondrial membrane potential, Ki-67 expression, and G0/G1 and G2/M phases of the cell cycle was observed. These effects were accompanied by the increase of GSH content and the reduction of SOD-1 and -2, GPX-1, and ROS release. Also, iNOS expression and NO release were inhibited, and pro-inflammatory cytokine gene expression was decreased, confirming the putative role of α-tocopherol against inflammation.

Conclusion: α-Tocopherol exerts protective effects in HDF which underwent oxidative stress by modulating the redox status, inflammation, iNOS-dependent NO release, and mitochondrial function. These observations have a potential role in the prevention and treatment of photoaging-related skin cancers.