Dermal Relief

CLINICAL STUDIES ON THE FOLLOWING INGREDIENTS:

Polypodium leucotomos

Mechanistic insights in the use of a Polypodium leucotomos extract as an oral and topical photoprotective agent

Abstract

Photoprotection is essential to prevent the deleterious effects of ultraviolet (UV) light, including skin cancer, photoaging and immunosuppression. Photoprotective agents can be classified according to their main mechanism of action. Some of them absorb or deflect UV photons (sunscreens), whereas others prevent or fix the deleterious effects of UV exposure. Here, we review recent evidence on the cellular and molecular mechanisms underlying the photoprotective effect of a Polypodium leucotomos fern extract (PL). PL is a natural mixture of phytochemicals endowed with powerful antioxidant properties. Its short-term effects include inhibition of reactive oxygen species production induced by UV radiation, DNA damage, isomerization and decomposition of trans-urocanic acid, prevention of UV-mediated apoptosis and necrosis, as well as degradative matrix remodeling, which is the main cause of photoaging. These short-term effects translate into long-term prevention of photoaging and photocarcinogenesis. A striking property is that PL can exert its effect when administered orally. Together, these effects postulate PL as a natural photoprotective agent and a potential adjuvant to phototherapy for various skin diseases.

Source: Gonzalez S, Gilaberte Y, Philips N. “Mechanistic insights in the use of a Polypodium leucotomos extract as an oral and topical photoprotective agent.” Photochem Photobiol Sci. (2010);9(4):559-63.

Beneficial regulation of matrix metalloproteinases and their inhibitors, fibrillar collagens and transforming growth factor-beta by Polypodium leucotomos, directly or in dermal fibroblasts, ultraviolet radiated fibroblasts, and melanoma cells

Abstract

The extracellular matrix (ECM) that gives tissue its structural integrity is remodeled in skin aging/photoaging and cancer via the increased expression/activities of matrixmetalloproteinases (MMP), inhibition of the tissue inhibitors of matrix metalloproteinases (TIMP), or inhibition of collagen synthesis. Transforming growth factor-beta (TGF-beta), a predominant regulator of the ECM, is inhibited in aging/photoaging and stimulated in carcinogenesis. P. leucotomos (fern) extract has potential to counteract these alterations via its antioxidant, anti-inflammatory and photoprotective properties. The goal of this research was to determine the efficacy of P. leucotomos to (a) directly inhibit MMP-1, 2, 3, and 9 activities, (b) inhibit MMP-2, and stimulate TIMPs, fibrillar collagens and TGF-beta in non-irradiated or ultraviolet (UV) radiated fibroblasts, and (c) inhibit MMPs and TGF-beta, and stimulate TIMPs in melanoma cells. To this purpose, we examined the direct effect of P. leucotomos (0-1%) on MMPs' activities, and its effects on the expression (protein and/or transcription levels) of (1) MMPs and TIMPs in dermal fibroblasts, and melanoma cells, (2) TGF-beta in non-irradiated, UVA (2.5 J/cm2) or UVB (2.5 mJ/cm2) irradiated fibroblasts, and melanoma cells, and (3) types I, III, and V collagen in non-irradiated or UV irradiated fibroblasts. P. leucotomos directly inhibited the activities of MMPs as well as the expression of MMPs in fibroblasts, and melanoma cells while stimulating the expression of TIMPs in these cells. P. leucotomos stimulated types I, III, and V collagen in non-irradiated fibroblasts, and types I and V collagen in UV radiated fibroblasts. P. leucotomos had predominant stimulatory effects on TGF-beta expression in non-irradiated or UV radiated fibroblasts, and inhibited TGF-beta expression in melanoma cells. The effects of P. leucotomos were largely similar to that of ascorbic acid. P. leucotomos demonstrated dual protective effects on the ECM via its inhibition of the ECM proteolytic enzymes and the stimulation of the structural ECM collagens. The effects of P. leucotomos on fibroblasts and melanoma cells may be partly via its cell-specific regulation of TGF-beta expression and partly via its antioxidant property. The intake or topical application of P. leucotomos may be beneficial to skin health, in aging and cancer prevention or treatment.

Source: Philips N, Conte J, Chen YJ, Natrajan P, Taw M, Keller T, Givant J, Tuason M, Dulaj L, Leonardi D, Gonzalez S. “Beneficial regulation of matrixmetalloproteinases and their inhibitors, fibrillar collagens and transforming growth factor-beta by Polypodium leucotomos, directly or in dermal fibroblasts, ultraviolet radiated fibroblasts, and melanoma cells.” Arch Dermatol Res. (2009);301(7):487-95.

Polypodium leucotomos extract in atopic dermatitis: a randomized, double-blind, placebo-controlled, multicenter trial

Abstract

Introduction: Topical corticosteroids are used to treat inflammation and relieve itching in atopic dermatitis, but their use is limited by adverse reactions.

Objectives: The main aim of this study was to investigate whether daily treatment with Polypodium leucotomos extract would reduce the use of topical corticosteroids in children and adolescents with atopic dermatitis. We also analyzed oral antihistamine use and changes in disease severity.

Patients and methods: We performed a phase IV randomized, double-blind, placebo-controlled, multicenter trial involving 105 patients aged between 2 and 17 years who were receiving topical corticosteroids to treat moderate atopic dermatitis. The patients were randomized to receive, in addition to their standard treatment, Polypodium leucotomos extract or placebo (both in capsule form) for 6 months. The percentage of days on which topical corticosteroids and other atopic dermatitis treatments were used was calculated.

Results: Use of Polypodium leucotomos extract did not significantly reduce the mean (SD) percentage of days on which topical corticosteroids were used (11% [12%] vs 12% [11%] for placebo). A significant reduction was, however, observed for oral histamine use (median percentage of days, 4.5% in the Polypodium leucotomos group and 13.6% in the placebo group [P= .038]). The percentage of patients who used oral antihistamines was also lower in the Polypodium leucotomos group.

Conclusion: Long-term treatment with Polypodium leucotomos extract has benefits for children and adolescents with atopic dermatitis who require pharmacologic treatment to reduce inflammation and relieve itching.

Source: Ramírez-Bosca A, Zapater P, Betlloch I, Albero F, Martínez A, Díaz-Alperi J, Horga JF; Grupo de Anapsos en Dermatitis Atópica y centros de realización del estudio. “Polypodium leucotomos extract in atopic dermatitis: a randomized, double-blind, placebo-controlled, multicenter trial.” Actas Dermosifiliogr. (2012);103(7):599-607.

Topical or oral administration with an extract of Polypodium leucotomos prevents acute sunburn and psoralen-induced phototoxic reactions as well as depletion of Langerhans cells in human skin

Abstract

Sunburn, immune suppression, photoaging, and skin cancers result from uncontrolled overexposure of human skin to solar ultraviolet radiation (UVR). Preventive measures, including photoprotection, are helpful and can be achieved by topical sunscreening agents. Polypodium leucotomos (PL) has been used for the treatment of inflammatory diseases and has shown some in vitro and in vivo inmunomodulating properties. Its beneficial photoprotective effects in the treatment of vitiligo and its antioxidant properties encouraged us to evaluate in vivo the potentially useful photoprotective property of natural extract of PL after topical application or oral ingestion. Twenty-one healthy volunteers [either untreated or treated with oral psoralens (8-MOP or 5-MOP)] were enrolled in this study and exposed to solar radiation for evaluation of the following clinical parameters: immediate pigment darkening (IPD), minimal erythema dose (MED), minimal melanogenic dose (MMD), and minimal phototoxic dose (MPD) before and after topical or oral administration of PL. Immunohistochemical assessment of CD1a-expressing epidermal cells were also performed. PL was found to be photoprotective after topical application as well as oral administration. PL increased UV dose required for IPD (P < 0.01), MED (P < 0.001) and MPD (P < 0.001). After oral administration of PL, MED increased 2.8 +/- 0.59 times and MPD increased 2.75 +/- 0.5 and 6.8 +/- 1.3 times depending upon the type of psoralen used. Immunohistochemical study revealed photoprotection of Langherhans cells by oral as well as topical PL. The observed photoprotective activities of oral or topical PL reveal a new avenue in examining the potentially useful field of systemic photoprotection and suggests that PL can be used as adjunct treatment and can make photochemotherapy and phototherapy possibly safe and effective when the control of cutaneous phototoxicity to PUVA or UVB is a limiting factor in such phototherapies.

Source: González S, Pathak MA, Cuevas J, Villarrubia VG, Fitzpatrick TB. “Topical or oral administration with an extract of Polypodium leucotomos prevents acute sunburn and psoralen-induced phototoxic reactions as well as depletion of Langerhans cells in human skin.” Photodermatol Photoimmunol Photomed. (1997);13(1-2):50-60.

Histidine

Feeding filaggrin: effects of l-histidine supplementation in atopic dermatitis

Abstract

Atopic dermatitis (AD), also known as eczema, is one of the most common chronic skin conditions worldwide, affecting up to 16% of children and 10% of adults. It is incurable and has significant psychosocial and economic impacts on the affected individuals. AD etiology has been linked to deficiencies in the skin barrier protein, filaggrin. In mammalian skin, l-histidine is rapidly incorporated into filaggrin. Subsequent filaggrin proteolysis releases l-histidine as an important natural moisturizing factor (NMF). In vitro studies were conducted to investigate the influence of l-histidine on filaggrin processing and barrier function in human skin-equivalent models. Our further aim was to examine the effects of daily oral l-histidine supplementation on disease severity in adult AD patients. We conducted a randomized, double-blind, placebo-controlled, crossover, nutritional supplementation pilot study to explore the effects of oral l-histidine in adult AD patients (n=24). In vitro studies demonstrated that l-histidine significantly increased both filaggrin formation and skin barrier function (P<0.01, respectively). Data from the clinical study indicated that once daily oral l-histidine significantly reduced (P<0.003) AD disease severity by 34% (physician assessment using the SCORingAD tool) and 39% (patient self-assessment using the Patient Oriented Eczema Measure tool) after 4 weeks of treatment. No improvement was noted with the placebo (P>0.32). The clinical effect of oral l-histidine in AD was similar to that of mid-potency topical corticosteroids and combined with its safety profile suggests that it may be a safe, nonsteroidal approach suitable for long-term use in skin conditions that are associated with filaggrin deficits such as AD.

Source: Tan SP, Brown SB, Griffiths CE, Weller RB, Gibbs NK. “Feeding filaggrin: effects of l-histidine supplementation in atopic dermatitis.” Clin Cosmet Investig Dermatol. (2017);10:403-411.

New Treatments for Atopic Dermatitis Targeting Skin Barrier Repair via the Regulation of FLG Expression

Abstract

Atopic dermatitis (AD) is one of the most common chronic, inflammatory skin disorders with a complex etiology and a broad spectrum of clinical phenotypes. Despite its high prevalence and effect on the quality of life, safe and effective systemic therapies approved for long-term management of AD are limited. A better understanding of the pathogenesis of atopic dermatitis in recent years has contributed to the development of new therapeutic approaches that target specific pathophysiological pathways. Skin barrier dysfunction and immunological abnormalities are critical in the pathogenesis of AD. Recently, the importance of the downregulation of epidermal differentiation complex (EDC) molecules caused by external and internal stimuli has been extensively emphasized. The purpose of this review is to discuss the innovations in the therapy of atopic dermatitis, including biologics, small molecule therapies, and other drugs by highlighting regulatory mechanisms of skin barrier-related molecules, such as filaggrin (FLG) as a crucial pathway implicated in AD pathogenesis.

Source: Dębińska A. “New Treatments for Atopic Dermatitis Targeting Skin Barrier Repair via the Regulation of FLG Expression.” J Clin Med. (2021);10(11):2506.

l-Histidine Supplementation in Adults and Young Children with Atopic Dermatitis (Eczema)

Abstract

Atopic dermatitis (AD) is an incurable, inflammatory skin condition that is prevalent (∼20%) in young children. There is an unmet clinical need, particularly in children, for safe interventions that target the etiology of the disease. Deficiencies in the skin barrier protein, filaggrin (FLG) have been identified as major predisposing factors in AD. In mammals, l-histidine is rapidly incorporated into epidermal FLG and subsequent FLG proteolysis releases l-histidine as an important natural moisturizing factor (NMF). It has therefore been hypothesized that l-histidine supplementation would be a safe approach to augment both FLG and the NMF, enhance skin barrier function, and reduce AD severity. In a clinical pilot study, adult subjects (n = 24) with AD took either a placebo or 4 g oral l-histidine daily for 8 wk. Unlike the placebo, l-histidine reduced AD (34% reduction in SCORing Atopic Dermatitis scores; P < 0.003) after 4 wk. Nine and 8 adverse events (AEs), and 1 and 0 severe AEs were recorded in the l-histidine or placebo groups, respectively, with no AE being causally related to l-histidine ingestion. A survey of adults (n = 98) taking 4 g l-histidine daily reiterated a lack of causal AEs and also reported a 33% reduction in topical corticosteroid use. A placebo-controlled, clinical pilot study conducted in young children with AD (n = 49; mean age 3.5 y) taking 0.8 g l-histidine daily, showed that eczema area and severity index scores were reduced by 49% (P < 0.02) at 12 wk, whereas a placebo had no effect. The children taking l-histidine had 50 minor AEs (compared with 39 on placebo), with 78% considered as "not," 18% "unlikely," and 4% "possibly" related to l-histidine ingestion. These studies indicate that at the levels reported, oral l-histidine supplementation is well tolerated and has potential as a safe intervention for long-term use in the management of AD in all age groups.

Source: Gibbs NK. “l-Histidine Supplementation in Adults and Young Children with Atopic Dermatitis (Eczema).” J Nutr. (2020);150(Suppl 1):2576S-2579S.

Vitamin D

The Impact of Vitamin D Levels on Inflammatory Status: A Systematic Review of Immune Cell Studies

Abstract

Chronic low-grade inflammation accompanies obesity and its related chronic conditions. Both peripheral blood mononuclear cells (PBMCs) and cell lines have been used to study whether vitamin D has immune modulating effects; however, to date a detailed systematic review describing the published evidence has not been completed. We therefore conducted a systematic review on the effect of vitamin D on the protein expression and secretion of inflammatory markers by human-derived immune cells. The review was registered at the International Prospective Register for Systematic Reviews (PROSPERO, Registration number CRD42015023222). A literature search was conducted using Pubmed, Science Direct, Scopus, Web of Science and Medline. The search strategy used the following search terms: Vitamin D or cholecalciferol or 1,25-dihydroxyvitamin or 25-hydroxy-Vitamin D and Inflam* or cytokine* and supplement* or cell*. These terms were searched in the abstract, title and keywords. Inclusion criteria for study selection consisted of human-derived immune cell lines or cellular studies where PBMCs were obtained from humans, reported in the English language, and within the time period of 2000 to 2015. The selection protocol was mapped according to PRISMA guidelines. Twenty three studies (7 cell line and 16 PBMCs studies) met our criteria. All studies selected except one used the active metabolite 1,25(OH)2, with one study using cholecalciferol and two studies also using 25(OH)D. Four out of seven cell line studies showed an anti-inflammatory effect where suppression of key markers such as macrophage chemotactic protein 1, interleukin 6 and interleukin 8 were observed. Fourteen of sixteen PBMC studies also showed a similar anti-inflammatory effect based on common inflammatory endpoints. Mechanisms for such effects included decreased protein expression of toll-like receptor-2 and toll-like receptor-4; lower levels of phosphorylated p38 and p42/42; reduced expression of phosphorylated signal transducer and activator of transcription 5 and decreased reactive oxygen species. This review demonstrates that an anti-inflammatory effect of vitamin D is a consistent observation in studies of cell lines and human derived PBMCs.

Source: Calton EK, Keane KN, Newsholme P, Soares MJ. “The Impact of Vitamin D Levels on Inflammatory Status: A Systematic Review of Immune Cell Studies.” PLoS One. (2015);10(11):e0141770.

Vitamin D and the skin: Focus on a complex relationship: A review

Abstract

The “sunshine” vitamin is a hot topic that attracted ample attention over the past decades, specially that a considerable proportion of the worldwide population are deficient in this essential nutrient. Vitamin D was primarily acknowledged for its importance in bone formation, however; increasing evidence point to its interference with the proper function of nearly every tissue in our bodies including brain, heart, muscles, immune system and skin. Thereby its deficiency has been incriminated in a long panel of diseases including cancers, autoimmune diseases, cardiovascular and neurological disorders. Its involvement in the pathogenesis of different dermatological diseases is no exception and has been the subject of much research over the recent years. In the current review, we will throw light on this highly disputed vitamin that is creating a significant concern from a dermatological perspective. Furthermore, the consequences of its deficiency on the skin will be in focus.

Source: Mostafa WZ, Hegazy RA. “Vitamin D and the skin: Focus on a complex relationship: A review.” J Adv Res. (2015);6(6):793-804.

The Effects of Oral Vitamin D Supplement on Atopic Dermatitis: A Clinical Trial with Staphylococcus aureus Colonization Determination

Abstract

Background: An increase in Staphylococcus aureus skin colonization in atopic dermatitis patients resulted from the reduction of cathelicidin production in these patients. Recently, an in vivo study demonstrated that vitamin D could stimulate cathelicidin production. Oral supplements of vitamin D might be beneficial in atopic dermatitis.

Objective: To determine the effects of oral vitamin D supplements on clinical impact including Staphylococcus aureus skin colonization evaluation in atopic dermatitis patients.

Material and method: Twenty-four atopic dermatitis patients were included in this double-blind, placebo-controlled study. They were randomly assigned into 2 groups for oral 2,000 IUs/day of vitamin D, supplement and placebo. The lesional swab culture for S. aureus was done at week 0, 2 and 4. Clinical outcomes were assessed by SCORAD score, mexameter for erythema index and konometer for conductance were done at week 0, 2 and 4. Serum vitamin D levels were also determined at week 0 and 4.

Results: Twenty patients completed the protocol. S. aureus skin colonization, SCORAD score and erythema index were significantly reduced from baseline to week 4for vitamin D treated group comparing with placebo (p = 0.022, 0.028 and 0.014, respectively). There was an inverse correlation between serum vitamin D levels with S. aureus skin colonization and SCORAD score (r = -1.0, p < 0.001).

Conclusion: Oral vitamin D supplement could reduce skin colonization of S. aureus and demonstrated the clinical improvement of patients with atopic dermatitis.

Source: Udompataikul M, Huajai S, Chalermchai T, Taweechotipatr M, Kamanamool N. “The Effects of Oral Vitamin D Supplement on Atopic Dermatitis: A Clinical Trial with Staphylococcus aureus Colonization Determination.” J Med Assoc Thai. (2015);98 Suppl 9:S23-30.

Vitamin D Status and Efficacy of Vitamin D Supplementation in Atopic Dermatitis: A Systematic Review and Meta-Analysis

Abstract

Recent literature has highlighted the possible role of vitamin D in atopic dermatitis (AD), and that vitamin D supplementation might help to treat AD. This study determined the relationship between vitamin D level and AD, and assessed the efficacy of vitamin D supplementation. We searched the MEDLINE, EMBASE, and Cochrane databases up to May 2015. Observational studies and randomized controlled trials were included based on the available data on the serum 25-hydroxyvitamin D (25(OH)D) level and quantified data available for severity assessed using the Scoring Atopic Dermatitis (SCORAD) index or Eczema Area and Severity Index (EASI) score. Compared with healthy controls, the serum 25(OH)D level was lower in the AD patients of all ages (standardized mean difference = −2.03 ng/mL; 95% confidence interval (CI) = −2.52 to −0.78), and predominantly in the pediatric AD patients (standardized mean difference = −3.03 ng/mL; 95% CI = −4.76 to −1.29). In addition, the SCORAD index and EASI score decreased after vitamin D supplementation (standardized mean difference = −5.85; 95% CI = −7.66 to −4.05). This meta-analysis showed that serum vitamin D level was lower in the AD patients and vitamin D supplementation could be a new therapeutic option for AD.

Source: Kim MJ, Kim SN, Lee YW, Choe YB, Ahn KJ. “Vitamin D Status and Efficacy of Vitamin D Supplementation in Atopic Dermatitis: A Systematic Review and Meta-Analysis.” Nutrients. (2016);8(12):789.

Vitamin E

Evaluation of dietary intake of vitamin E in the treatment of atopic dermatitis: a study of the clinical course and evaluation of the immunoglobulin E serum levels

Abstract

Background: Vitamin E (VE) is a potent antioxidant that can improve the immune macrophage-mediated response, decrease the production and/or release of prostaglandins in humans, and decrease the serum levels of immunoglobulin E (IgE) in atopic subjects.

Aim: To compare the effects of placebo (PL) and VE intake (400 IU/day) on subjective symptoms and serum IgE levels in 96 subjects with atopic dermatitis.

Materials and methods: A single-blind clinical analysis was performed on 96 subjects randomly divided into two groups. Fifty subjects were given orally 400 IU (268 mg) of VE of natural origin, once a day for 8 months, and 46 took PL for the same period. Complete blood count, serum IgE levels, radioallergosorbent test (RAST) score, antinuclear antibodies (ANA), and biochemical analysis were obtained at the time of enrollment and every 15 days during the 8 months of the study. To evaluate VE therapy, a questionnaire was sent to each subject for completion at the end of the study.

Results: The results were as follows: (A) four subjects treated with VE worsened, compared to 36 in the PL group; (B) six subjects in the VE group and five in the PL group showed no change; (C) slight improvement was observed in 10 subjects in the VE group and four in the PL group; (D) 23 of the 50 subjects treated with VE showed great improvement, compared to only one in the PL group; and (E) there was almost complete remission of atopic dermatitis in seven of the 50 subjects in the VE group, but none in the PL group. Females showed less progression of atopic dermatitis than males in both groups and a higher percentage of almost complete remission (five females and two males). The range of serum IgE levels varied markedly from 1005 to 490 IU/mL in the VE group and from 1239 to 812 IU/mL in the PL group over 8 months. Subjects with great improvement and near remission of atopic dermatitis in the VE group demonstrated a decrease of 62% in serum IgE levels based on initial conditions, while, in subjects taking PL, the difference was approximately 34.4%. No complications were observed in either group. A remarkable improvement in facial erythema, lichenification, and the presence of apparently normal skin was reported. Eczematous lesions healed mostly as a result of decreased pruritus.

Conclusions: The correlation between VE intake, IgE levels, and the clinical manifestations of atopy indicates that VE could be an excellent therapeutic tool for atopic dermatitis.

Source: Tsoureli-Nikita E, Hercogova J, Lotti T, Menchini G. “Evaluation of dietary intake of vitamin E in the treatment of atopic dermatitis: a study of the clinical course and evaluation of the immunoglobulin E serum levels.” Int J Dermatol. (2002);41(3):146-50.

Randomized controlled trial using vitamins E and D supplementation in atopic dermatitis

Abstract

Background: Atopic dermatitis is a chronically relapsing, highly pruritic and inflammatory skin disease. This study was done to assess the effects of vitamins D and E supplementation on the clinical manifestation of atopic dermatitis.

Methods: Forty-five atopic dermatitis patients were included in a randomized, double-blind, placebo-controlled trial. They were randomly divided into four groups and treated for 60 days: group P (n = 11), vitamins D and E placebos; group D (n = 12), 1600 IU vitamin D(3) plus vitamin E placebo; group E (n = 11), 600 IU synthetic all-rac-α-tocopherol plus vitamin D placebo; and group DE (n = 11), 1600 IU vitamin D(3) plus 600 IU synthetic all-rac-α-tocopherol. Serum 25(OH) vitamin D and plasma α-tocopherol were determined before and after the trial. The clinical improvement was evaluated with SCORing Atopic Dermatitis (SCORAD). Data were analyzed by analysis of variance (ANOVA) and Kruskal-Wallis tests.

Results: SCORAD was reduced after 60 days in groups D, E and DE by 34.8%, 35.7% and 64.3%, respectively (p = 0.004). Objective SCORAD also showed significant improvement. There was a positive correlation between SCORAD and intensity, objective, subjective and extent (p < 0.001). We found a significant negative association between plasma α-tocopherol and SCORAD, intensity, objective and extent (p = 0.02).

Conclusion: This study supports the contributing and beneficial effects of vitamins D and E in the treatment of atopic dermatitis.

Source: Javanbakht MH, Keshavarz SA, Djalali M, Siassi F, Eshraghian MR, Firooz A, Seirafi H, Ehsani AH, Chamari M, Mirshafiey A. “Randomized controlled trial using vitamins E and D supplementation in atopic dermatitis.” J Dermatolog Treat. (2011);22(3):144-50.

Ashwagandha

Adaptogenic and Anxiolytic Effects of Ashwagandha Root Extract in Healthy Adults: A Double-blind, Randomized, Placebo-controlled Clinical Study

Abstract

Background: Stress, anxiety and impeded sleep are a frequent feature of life in modern societies. Across socio-economic strata, stress, anxiety and ineffective sleep detract from healthful living and serve as precursors of various ailments. The use of herbs to offset these antecedents and outcomes has greatly increased in recent years. Ashwagandha, an adaptogenic Ayurvedic herb, has been often used to combat and reduce stress and thereby enhance general wellbeing. While there have been other studies documenting the use of Ashwagandha for stress resistance, this is the first study to use a high-concentration root extract while also varying the dosage substantially. Therefore, this is the first study to offer insight into dose-response of a high concentration root extract.

Material and methods: In this eight-week, prospective, randomized, double-blind, placebo-controlled study, the stress-relieving effect of Ashwagandha root extract was investigated in stressed healthy adults. Sixty male and female participants with a baseline perceived stress scale (PSS) score >20 were randomized to receive capsules of Ashwagandha extract 125 mg, Ashwagandha extract 300 mg or identical placebo twice daily for eight weeks in a 1:1:1 ratio. Stress was assessed using PSS at baseline, four weeks and eight weeks. Anxiety was assessed using the Hamilton-Anxiety (HAM-A) scale and serum cortisol was measured at baseline and at eight weeks. Sleep quality was assessed using a seven-point sleep scale. A repeat measures ANOVA (general linear model) was used for assessment of treatment effect at different time periods. Post-hoc Dunnett’s test was used for comparison of two treatments with placebo.

Results: Two participants (one each in 250 mg/day Ashwagandha and placebo) were lost to follow-up and 58 participants completed the study. A significant reduction in PSS scores was observed with Ashwagandha 250 mg/day (P < 0.05) and 600 mg/day (P < 0.001). Serum cortisol levels reduced with both Ashwagandha 250 mg/day (P < 0.05) and Ashwagandha 600 mg/day (P < 0.0001). Compared to the placebo group participants, the participants receiving Ashwagandha had significant improvement in sleep quality.

Conclusion: Ashwagandha root aqueous extract was beneficial in reducing stress and anxiety.

Source: Salve J, Pate S, Debnath K, Langade D. “Adaptogenic and Anxiolytic Effects of Ashwagandha Root Extract in Healthy Adults: A Double-blind, Randomized, Placebo-controlled Clinical Study.” Cureus. (2019);11(12):e6466.

Efficacy and Tolerability of Ashwagandha Root Extract in the Elderly for Improvement of General Well-being and Sleep: A Prospective, Randomized, Double-blind, Placebo-controlled Study

Abstract

Background: Ashwagandha is an excellent adaptogen that is being used since ancient times in Ayurvedic medicine. Traditionally, it is used for various ailments and general well-being, including the treatment of geriatric patients. Managing quality of life (QoL) remains a challenge for the elderly population, especially joint pain management, sleep, and general well-being. With a growing global elderly population, QoL management with efficient medication and supplementation is the major healthcare requirement.

Objective: The objective of this study was to assess the safety, efficacy, and tolerability of Ashwagandha (Withania somnifera (L.) Dunal.) root extract on the improvement of general health and sleep in elderly people.

Methods: This 12-week, prospective, randomized, double-blind, placebo-controlled study was conducted on individuals of either gender aged between 65-80 years. Participants were randomized to receive Ashwagandha root extract at a dose of 600 mg/day (n = 25) orally, or identical placebo capsules with the same dose (n = 25) for 12 weeks. Efficacy was assessed using the WHOQOL-BREF questionnaire, sleep quality, mental alertness on rising, and Physician’s Global Assessment of Efficacy to Therapy (PGAET). The safety and tolerability were assessed using the clinical adverse events reporting and Patient's Global Assessment of Tolerability to Therapy (PGATT).

Results: Statistically significant (P<0.0001) improvement was observed in the Ashwagandha treatment group compared to the placebo. The mean (SD) total score of WHOQOL-BREF improved from 140.53 (8.25) at the baseline to 161.84(9.32) at the end of the study. The individual domain scores were also improved. At baseline, the sleep quality and the mental alertness on rising were comparatively low in both the groups. However, upon intervention, a significant increase in the quality of sleep (P<0.0001) and mental alertness (P<0.034) was observed in the Ashwagandha treatment group when compared to the placebo group. Overall improvement was observed for the general wellbeing, sleep quality, and mental alertness in the study population. The experimental group population displayed good tolerability to the test product and it was reported as safe and beneficial by the study participants.

Conclusion: The study outcomes suggest that Ashwagandha root extract was efficient in improving the QoL, sleep quality, and mental alertness as self-assessed by the elderly participants. The recommended dose used in this study could be effective for the elderly population.

Source: Kelgane SB, Salve J, Sampara P, Debnath K. “Efficacy and Tolerability of Ashwagandha Root Extract in the Elderly for Improvement of General Well-being and Sleep: A Prospective, Randomized, Double-blind, Placebo-controlled Study.” Cureus. (2020);12(2):e7083.

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