Topical Application Of Vitamin Research Articles

Topical application of vitamin D cream in particiants with inflammatory acne due to vitamin D deficiency

Acne vulgaris (AV) represents a chronic inflammatory condition affecting pilosebaceous units, characterized by a multifactorial etiology. AV can manifest as both inflammatory and non-inflammatory skin lesions. Non-inflammatory acne is termed a comedone, which can be either closed (whiteheads) or open (blackheads). Inflammatory acne encompasses papules, pustules, nodules, and pseudocysts. The most common regions for acne occurrence are the facial region (90%), thoracic area (14%), and dorsal region (60%). In the study involving transdermal application of vitamin D cream (applied twice daily; morning and evening) in subjects with inflammatory acne due to vitamin D deficiency, 33 participants took part, comprising 8 males and 25 females. The age group most affected was 18-25 years (adolescent age), followed by a lesser impact in the 26-30 age group, and the lowest incidence observed in the late 36-45 age group. Among males, facial and thoracic regions were most affected by inflammatory acne (37.5%), while among females, the facial region showed a higher percentage of 54%, and the thoracic area was at 40%, with a minimal impact on the dorsal region (M=25%; F=8%). Reductions in inflammatory acne ranged from 100% to 10%, with substantial improvements noted in the male population, achieving 100% and 80% reduction (100% reduction: facial region 25%, thoracic area 12.5%, 80% reduction: dorsal region 25%). Similarly, the female group, with a larger sample size (25 participants), demonstrated significant reductions (100% reduction: facial region 36%, thoracic area 24%, 80% reduction: dorsal area 4%). Overall, improvements were evident in all participants, with none falling below a 30% reduction, indicating remarkable outcomes after one month of vitamin D cream use. Numerous factors contribute to the onset of inflammatory acne, with this study specifically highlighting vitamin D deficiency in the blood. Other indications include the occurrence of polycystic ovaries and reduced thyroid function in women, heightened stress, and prostate issues in men. Reduced or deficient vitamin D levels may be associated with further immune system suppression, activating the aforementioned factors. This research marks a significant stride in uncovering the manifold health benefits of vitamin D. Keywords: acne, vitamin D, participants

TRANSDERMAL APPLICATION OF VITAMIN D AND ITS EFFECTS ON PSORIASIS

Psoriasis represents a disorder of skin hypoproliferation, where vitamin D is frequently utilized in its treatment. Ultraviolet (UV) radiation stimulates the synthesis of vitamin D3 (cholecalciferol) in the epidermis. This compound undergoes further conversion into active metabolites, specifically 25-hydroxycholecalciferol and 1,25-hydroxycholecalciferol, which play crucial roles in skin health. However, in conditions like psoriasis, disruptions in skin functioning impede the cutaneous production of vitamin D, initiating a detrimental cycle. This disruption leads to a gradual reduction in vitamin D levels throughout the body, consequently destabilizing skin homeostasis. Topical application of vitamin D enables a substantial reduction in psoriasis on target areas of the body such as the scalp, joints, hands and lumbar region. The research records reductions of 100%, 80%, and 50% in the mentioned regions.

Lasers & topical vitamin C: scars in ehlers-danlos

Background: Hypermobile Ehlers-Danlos Syndrome (hEDS) is a connective tissue disorder with cutaneous manifestations including poor wound healing and atrophic scar formation. There is evidence supporting the use of topical vitamin C and laser for scar revisions, but limited reports of using topical vitamin C in scar revisions in patients with hEDS. Objective: To present a case where topical vitamin C applied post-laser treatment resulted in improved healing and aesthetic outcomes in a patient with a connective tissue disorder. Methods: We present a case of treatment of atrophic and hypertrophic scars in a patient with hEDS with ablative fractional laser, pulsed dye laser, and post-procedural topical vitamin C. We discuss the patient’s treatments, outcomes, and previous literature on the matter. Results: This patient had markedly improved wound healing after topical application of vitamin C post-laser treatment with no complications. Additionally, the patient had improved aesthetic outcomes with topical vitamin C and laser treatment just after one session. Conclusion: This case suggests that hEDS scars may be safely treated with lasers when combined with post-procedural topical vitamin C.

Scientific validation of three-dimensional stereophotogrammetry compared to the IGAIS clinical scale for assessing wrinkles and scars after laser treatment

Measuring outcomes from treatments to the skin is either reliant upon patient’s subjective feedback or scale-based peer assessments. Three-Dimensional stereophotogrammetry intend to accurately quantify skin microtopography before and after treatments. The objective of this study is comparing the accuracy of stereophotogrammetry with a scale-based peer evaluation in assessing topographical changes to skin surface following laser treatment. A 3D stereophotogrammetry system photographed skin surface of 48 patients with facial wrinkles or scars before and three months after laser resurfacing, followed immediately by topical application of vitamin C. The software measured changes in skin roughness, wrinkle depth and scar volume. Images were presented to three observers, each independently scoring cutaneous improvement according to Investigator Global Aesthetic Improvement Scale (IGAIS). As for the results, a trend reflecting skin/scar improvement was reported by 3D SPM measurements and raters. The percentage of topographical change given by the raters matched 3D SPM findings. Agreement was highest when observers analysed 3D images. However, observers overestimated skin improvement in a nontreatment control whilst 3D SPM was precise in detecting absence of intervention. This study confirmed a direct correlation between the IGAIS clinical scale and 3D SPM and confirmed the efficacy and accuracy of the latter when assessing cutaneous microtopography alterations as a response to laser treatment.

Comparative Study on the Outcome of Periorbital Wrinkles Treated with Laser-Assisted Delivery of Vitamin C or Vitamin C Plus Growth Factors: A Randomized, Double-blind, Clinical Trial

BackgroundDespite promising results, laser-assisted drug delivery (LADD) is not yet considered as standard therapies and published data rely mainly on laboratory tests, animal experiments or cadaver skin.ObjectivesThis double-blind, prospective, randomized clinical trial investigates the impact in topical application of vitamin C and a cosmeceutical containing growth factors (GFs) on periorbital wrinkles primarily treated with laser skin resurfacing.Material and MethodsIn total, 149 female patients with periorbital wrinkles were consented and randomized into two study groups, R-C (receiving vitamin C only) and R-CGF (receiving vitamin C and a cosmeceutical containing growth factors). The statistical analysis evaluated the efficacy of each treatment regimen using software readouts provided by a three-dimensional stereophotogrammetry system prior to treatment and three months after the procedure. Results were compared to confirm if there was a significant change in the skin roughness and the average depth of the wrinkles between the two groups after treatment.ResultsThere was a significant reduction in both skin roughness and average depth of the wrinkles in the group treated with vitamin C and growth factors (p <0.01) than those treated with LADD followed by topical application of vitamin C alone. There were no cutaneous reactions or adverse systemic reactions observed in this study related to LADD with vitamin C and GFs.ConclusionControlled laser application might have a great potential to facilitate the absorption of exogenous macromolecules by the skin. Periorbital wrinkles were reduced in both groups, but LADD using vitamin C and GFs provided significantly better results.Level of Evidence IIThis journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Wound healing effects of topical Vitamin K: A randomized controlled trial.

BACKGROUND:The incidence of acute and chronic wounds has rapidly increased which treatment remains as health problem. Previously, we reported the healing effect of Vitamin K in experimental animal models. The aim of this study was to investigate the effects of topical Vitamin K on skin wound healing process in patients.MATERIALS AND METHODS:Sixty-three patients with indication for high-frequency electrocautery were enrolled in this randomized controlled trial. The patients were divided randomly into three groups. All the patients underwent high-frequency electrocautery treatment. Then, the patients in the A group received 1% Vitamin K cream, the patients in the B group received 1% phenytoin cream. Furthermore, the patients in the control group received Eucerin. The wound status (width and the time of recovery) and complications in the three groups were evaluated 2 weeks after procedure by a dermatologist.RESULTS:The effects produced by the topical Vitamin K showed a significant (P < 0.05) healing when compared with Eucerin group in parameters such as wound contraction and time to full recovery. Moreover, the healing time did not differ between phenytoin and Vitamin K groups (P = 0.16).CONCLUSION:A randomized, controlled trial suggests that topical application of Vitamin K significantly reduces healing time in patients.

Topical applications of vitamin D on implant surface for bone‐to‐implant contact enhance: a pilot study in dogs part II

The aim of this study was to evaluate the effect of topical application of vitamin D over implant surface, placed immediately to the extraction, throughout histological and histomorphometric analysis of peri-implant tissue. Six American foxhound dogs were used in the study. Mandibular premolar distal roots were extracted. Twenty-four immediate conical C1 implants (MIS, Barlev, Israel) were randomly assigned to the distal site on each site of the mandible in three groups: (Group CI) 12 titanium implants alone; (Test Group DI) 12 titanium implants supplemented with vitamin D. Prior to implanting, test implants (DI) were submerged in vitamin D 10% solution. No treatment was applied at control implants (CI). After 12weeks, animals were sacrificed. Block sections were obtained and processed for mineralized ground sectioning. Bone-to-implant contact (Total BIC and BIC%), new bone formation (NBF), interthread bone (ITB), and histological linear measurements (HLM) were analyzed. At 12weeks, all implants were clinically stable and histologically osseointegrated. BIC evaluation showed Total BIC mean and SD values for DI (48.96±2.14), CI (44.56±1.75) (P<0.05), BIC% DI (43.59±0.98), and CI (42.67±9.26) (P>0.05). For interthread bone formation, values were as follows: DI (15.21±3.87), CI (14.79±1.45) (P>0.05), no statistically differences. Regarding peri-implant new bone formation, no statistically differences could be found between the two groups DI (31.87±1.23), CI (27.18±2.38) (P>0.05). For linear measurements, test group (DI) showed statistically significant less buccal crestal bone loss (CBL) DI (0.37±0.12)*, CI (1.26±0.8) (P<0.05), and vitamin D implants showed less lingual junctional epithelium DI (1.58±0.43)*, CI (2.18±0.48) (P<0.05). No differences were observed in the buccal mucosa. With the limitation of animal studies, topical application of vitamin D on dental implants could reduce crestal bone loss and increase 10% more bone-to-implant contact at 12-week follow-up period.

Increased nitric oxide level in diabetic rats from vitamin C supplementation: an in vivo detection using diaminofluorescein

Background: Vitamin C is of clinical benefit for improvement of impaired endothelial functions in diabetes, but its direct effect on nitric oxide (NO) available in endothelial cells during diabetes as yet remains unclear. Objective: To examine the correlation between level of bioavailable NO and arteriolar vasodilation under the direct effect of vitamin C, using a novel NO-sensitive fluorescent indicator in diabetic rats. Methods: Male Spraque-Dawley rats (200-250g body weight) were used for the experiment. The rats were divided into control (CON) and diabetic rats (DM). The diabetes was induced in rats by injection of streptozotocin (STZ) (50 mg/kg body weight). The direct effects of vitamin C administration on NO bioavailability were examined using a buffer solution containing 4,5-diaminofluorescein-diacetate (DAF-2DA) and acetylcholine (Ach) with or without vitamin C in Krebs-Ringer solution. Twenty minutes after the buffer solution was superfused on the rat mesentery, the changes in DAF-2T fluorescence intensities were examined along the arteriolar walls. By visualizing the microcirculation using FITC-dextran, Ach-induced vasodilation of the arterioles (15 to 35 μm in diameter) was measured using Image Pro-Plus Software. The analysis was made after pre-constriction with norepinephrine, and after topical application of vitamin C (ascorbic acid) on the mesentery and following topical application of Ach. Results: DAF-2DF was a NO-sensitive fluorescent indicator that did not make the microvascular walls visible without endothelial activation by Ach. The administration of vitamin C increased Ach-evoked vasodilation in CON and DM groups. Twenty minutes after vitamin C administration, the DAF-2T fluorescence intensities increased significantly in both groups. Conclusion: Vitamin C improved diabetes-induced endothelial dysfunction by enhancing NO bioavailability. The level of bioavailable NO and endothelium-dependent vasodilation were highly correlated.

Cause and Possible Treatments of Foot Lesions in Captive Syrian Hamsters (Mesocricetus auratus).

Syrian hamsters (Mesocricetus auratus) run extensively in exercise wheels. This running may cause paw lesions. Three treatments of these wounds (topical application of vitamin E, wheel blocking, and a combination of both) were compared using both sexes. A pretreatment period with or without wheels lasted 15 days and the ensuing treatment period lasted 45 days. At the end of the pre-treatment period, none of the animals without wheels had paw wounds, whereas at least 75% of the females and 100% of the males with wheels did. Females had fewer and smaller wounds than males at this point. At the end of the treatment period, no effect of vitamin E could be discerned, but significant wound healing occurred after wheel blocking in both males and females. Wheel blocking is an easy way to prevent or treat paw wounds, but it presents problems in terms of animal welfare, as wheels are an important cage enrichment for hamsters.

Treatment of pigmented lesions of neurofibromatosis 1 with intense pulsed–radio frequency in combination with topical application of vitamin D3 ointment

Cafe-au-lait spots and pigmented freckling are found in most of patients with neurofibromatosis 1 (NF1). Although many modalities have been used for treating the pigmented lesions, the response to treatment has been variable. Therefore, we performed the treatment of pigmented lesions with NF1 by intense pulsed-radio frequency (IPL-RF) in combination with topical application of vitamin D(3) ointment. Eight patients were treated in this study and the improvement was moderate to good in six cases (75%) although the response was relatively mild. Thus, results from our study indicate that IPL-RF irradiation in combination with topical application of vitamin D(3) ointment would be useful as new modalities, especially for treatment of numerous small pigmented lesions in patients with NF1. Although further studies with large groups of patients should be performed for a better conclusion, it could improve quality of life with NF1 patients who are concerned with serious cosmetic and social problems.

Clinical and instrumental evaluation of topical application of vitamin C on skin whitening effect

Clinical and instrumental evaluation of topical application of vitamin C on skin whitening effect

Improvement of Pigmented Fleckling of Neurofibromatosis 1 (NF1) with Photo RF Irradiation in Combination with Topical Application of Vitamin D3 Ointment

Improvement of Pigmented Fleckling of Neurofibromatosis 1 (NF1) with Photo RF Irradiation in Combination with Topical Application of Vitamin D₃ Ointment

A chemiluminescence study of UVA-induced oxidative stress in human skin in vivo.

Oxidative stress is defined as an imbalance between pro-oxidants and antioxidants in favor of pro-oxidants. Photon emission (also called chemiluminescence) has been widely used to study oxidative stress in biological systems in vitro. In vivo chemiluminescence has been proposed as a non-invasive method to assess oxidative stress in the skin. UVA (320-400 nm part of the ultraviolet radiation) exposure is generally accepted as a source of oxidative stress in the skin. In this study, UVA-induced oxidative stress was studied by using an in vivo chemiluminescence detection method. First, the dose response and the fluence rate response of the UVA-induced oxidative stress in human skin were investigated by examining the decay kinetics of the chemiluminescence signal following UVA exposure. A kinetic model was proposed to help differentiate these two responses. We found that the initial burst of the chemiluminescence signal depended on the UVA fluence rate, whereas the decay of the signal following exposure can be related to the UVA dose involved. Second, a significant reduction of UVA-induced chemiluminescence signal was observed after tape-stripping, indicating that stratum corneum is a major source of UVA-induced oxidative stress in the skin. Furthermore, the oxygen dependence of UVA-induced chemiluminescence signal was also confirmed by application of a pressure cuff, implying that some of the oxidative stress occurs in the deeper layers of the skin. Finally, topical application of vitamin C before exposure significantly reduced the UVA-induced chemiluminescence signal. We thus conclude that chemiluminescence is an effective method to assess the oxidative stress induced by UVA in human skin in vivo.

Topical Antioxidant Vitamins C and E Prevent UVB-Radiation-Induced Peroxidation of Eicosapentaenoic Acid in Pig Skin

Eicosapentaenoic acid protects against UV-radiation-induced immunosuppression and photocarcinogenesis, but it is also prone to oxidative degradation, which may reduce or abolish its beneficial effects. The protective effect of topically applied vitamin E, vitamin C, or both against UVB-radiation-induced lipid peroxidation in the presence of eicosapentaenoic acid was investigated using an ex vivo pig skin model. Changes in the bioavailability of both antioxidants induced by UV radiation were studied in different skin compartments. The UVB-radiation dose used (25 kJ/m2) was similar to that required to induce immunosuppression in BALB/c mice. Exposure of pig skin with an epidermal eicosapentaenoic acid content of 1.0 +/- 0.3 mol% to UVB radiation resulted in an 85% increase of epidermal lipid peroxidation (P < 0.005). Topical application of vitamin E or vitamin C 60 min prior to UVB irradiation resulted in a major increase in both antioxidants in the stratum corneum and viable epidermis (P < 0.05). Vitamin E and vitamin C completely protected against UVB-radiation-induced lipid peroxidation (P < 0.005), but compared to vitamin E, a 500-fold higher vitamin C dose was needed. UVB irradiation induced a vitamin E consumption of up to 100% in the stratum corneum and viable epidermis, and a vitamin C consumption of only 21% in the stratum corneum. Simultaneously applied vitamin E and vitamin C also completely protected against UVB-radiation-induced lipid peroxidation (P < 0.05), and lower antioxidant doses were needed compared to vitamin E or vitamin C alone. In the presence of vitamin C, epidermal vitamin E was more stable upon UVB irradiation (P < 0.05), suggesting interaction between vitamin E and vitamin C. In conclusion, topically applied vitamin E and/or vitamin C efficiently protect against UVB-radiation-induced lipid peroxidation in the presence of eicosapentaenoic acid. The beneficial biological effects of eicosapentaenoic acid may therefore be improved if vitamin E and/or vitamin C are present in sufficient amounts. The ex vivo pig skin model provides a useful tool for assessing short-term biochemical effects related to UVB radiation, without the use of living experimental animals.

Effects of Topical Vitamin E on Keratocyte Apoptosis after Traditional Photorefractive Keratectomy

Purpose: To evaluate the keratocyte apoptosis and effects of topical vitamin E on keratocyte apoptosis after photorefractive surgery. Methods: Rabbits were divided into 7 groups, and all groups were compared with controls after epithelial scraping, epithelial scrape and photorefractive keratectomy (PRK) (traditional PRK), transepithelial PRK, production of a corneal flap with microkeratome and laser-assisted in situ keratomileusis (LASIK). The effects of topical Vitamin E treatment were investigated in the traditional PRK group. The terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labelling assay (to detect DNA fragmentation in situ) and light microscopy have been used to detect apoptosis in rabbit cornea. Results: Transepithelial PRK induced minimal keratocyte apoptosis, less than in all other refractive surgical procedures. The greatest amount of keratocyte apoptosis was observed after traditional PRK (p = 0.001), therefore we tested the effects of topical vitamin E in this group. The number of apoptotic keratocytes significantly reduced after vitamin E therapy (p < 0.005). Conclusion: Keratocytes undergo apoptosis after refractive surgery in response to mechanical epithelial removal, preparing of corneal flap and excimer laser stromal photoablation. The topical application of vitamin E immediately after surgery can prevent keratocyte apoptosis, and this result suggests that free radicals may be partly responsible for keratocyte apoptosis after excimer laser keratectomy.

Topical application of vitamin A to oral leukoplakia - a clinical case series

Due to the possibility of malignant transformation of oral leukoplakia, these lesions must be assessed and managed closely and, if not resolved, must be reassessed on a regular basis. This study evaluated the use of topical 0.05% vitamin A (tretinoin) acid gel for the treatment of oral leukoplakia. Tretinoin was applied topically 4 times a day for the management of non-malignant oral white lesions in 26 patients. The clinical response was evaluated in all patients and post-treatment biopsies were performed in ten patients. The mean age of the patients at the time of diagnosis was 62 years. Of the 26 patients, 50% were tobacco users. Patients were followed for a mean of 23 months. Approximately 27% of the patients had a complete clinical remission. Recurrence of leukoplakia was observed in approximately 40% of patients, in whom complete clinical remission occurred if topical applications were discontinued. A 50% reduction in the clinical grade of leukoplakia from a mean of 2.8 to 1.4 on a scale ranging from 0 (no leukoplakia) to 4 (speckled leukoplakia) was observed. When the pre-treatment and post-treatment biopsies from 10 patients were evaluated, no change in the mean histologic grade (between mild and moderate dysplasia) was noted; however, some reduction in the histologic grade was noted in 3 of these patients (30%). The use of topical vitamin A acid showed a limited effect in controlling oral leukoplakia. Further studies are needed to establish the appropriate indication, efficacy and best choice for chemoprevention agents. Close follow-up of all patients with oral leukoplakia is required. Henk Tideman

Topical application of vitamin A to oral leukoplakia — a clinical case series

Topical application of vitamin A to oral leukoplakia — a clinical case series

PHOTOPROTECTIVE ACTIONS OF TOPICALLY APPLIED VITAMIN E*

Topical application of vitamin E has been shown to decrease the incidence of ultraviolet (UV)-induced skin cancer in mice. Vitamin E provides protection against UV-induced skin photodamage through a combination of antioxidant and UV absorptive properties. Topical application of α-tocopherol on mouse skin inhibits the formation of cyclobutane pyrimidine photoproducts. However, topically applied α-tocopherol is rapidly depleted by UVB radiation in a dose-dependent manner. The photooxidative fate of the α-tocopherol depends on the local environment of the vitamin E. α-Tocopherol quinone and α-tocopherol quinone epoxides are principal photoproducts of vitamin E that has penetrated into the epidermal layer of the skin, whereas tocopherol dimers and trimers are formed from α-tocopherol in a bulk phase at the skin surface. Dimer and trimer products may participate in prevention of UV-induced photodamage.

Hydrolysis of RRR-α-tocopheryl acetate (vitamin E acetate) in the skin and its UV protecting activity (an in vivo study with the rat)

Vitamin E acetate is often used rather than vitamin E as an ingredient of skin care products and dermatological preparations, because it lacks the free phenolic OH group. However, because of this the acetate as such is biologically inactive. In spite of this intrinsic inactivity, the skin is protected against the harmful effects of sunlight after topical application of vitamin E acetate. Therefore it is supposed that hydrolysis takes place in the skin and that the reaction product, the radical scavenger vitamin E, is responsible for the protection observed. In this in vivo study with the rat, we have investigated the hydrolysis of RRR-α-tocopheryl acetate (vitamin E acetate) in the epidermis in relation to UV radiation protection. (As a measure of protection, we used the UV-induced binding of 8-methoxypsoralen to epidermal biomacromolecules.) After a period of 5 h from a single application of vitamin E acetate, hydrolysis into free vitamin E was not observed. No protection was found at this time point, corresponding with the absence of vitamin E. After treatment for 5 days, consisting of one topical application daily, the percentage of acetate present in the stratum corneum which was hydrolysed into free vitamin E was less than 1%, whereas the corresponding value for the viable layer of the epidermis was about 5%. The hydrolysis of vitamin E acetate in the epidermis proceeded very slowly. As a result, the absolute amount of free vitamin E, found in the total epidermis after treatment for 5 days with the acetate, was only a few times higher than the normal level. Yet, this very small amount of free vitamin E proved to be sufficient for maximal protection in this animal model. The results show that vitamin E acetate acts as a prodrug, which very slowly releases minute amounts of active vitamin E.

Hydrolysis of RRR-α-tocopheryl acetate (vitamin E acetate) in the skin and its UV protecting activity (an in vivo study with the rat)

Vitamin E acetate is often used rather than vitamin E as an ingredient of skin care products and dermatological preparations, because it lacks the free phenolic OH group. However, because of this the acetate as such is biologically inactive. In spite of this intrinsic inactivity, the skin is protected against the harmful effects of sunlight after topical application of vitamin E acetate. Therefore it is supposed that hydrolysis takes place in the skin and that the reaction product, the radical scavenger vitamin E, is responsible for the protection observed. In this in vivo study with the rat, we have investigated the hydrolysis of RRR-α-tocopheryl acetate (vitamin E acetate) in the epidermis in relation to UV radiation protection. (As a measure of protection, we used the UV-induced binding of 8-methoxypsoralen to epidermal biomacromolecules.) After a period of 5 h from a single application of vitamin E acetate, hydrolysis into free vitamin E was not observed. No protection was found at this time point, corresponding with the absence of vitamin E. After treatment for 5 days, consisting of one topical application daily, the percentage of acetate present in the stratum corneum which was hydrolysed into free vitamin E was less than 1%, whereas the corresponding value for the viable layer of the epidermis was about 5%. The hydrolysis of vitamin E acetate in the epidermis proceeded very slowly. As a result, the absolute amount of free vitamin E, found in the total epidermis after treatment for 5 days with the acetate, was only a few times higher than the normal level. Yet, this very small amount of free vitamin E proved to be sufficient for maximal protection in this animal model. The results show that vitamin E acetate acts as a prodrug, which very slowly releases minute amounts of active vitamin E.