Asthma in Vitamin K points of view

By Kyle J. Norton

The widespread of incidence of asthma over large 20 years in South East Asian population, specially in children and aging group has caused some concerns to the government and scientific community. It may be due to over intake in artificial ingredients, polluted environment as well as intake foods triggering the inflammatory allergens.
Vitamin K(K1, phylloquinone; K2, menaquinones), is a fat soluble vitamin, found abundantly in leafy green vegetables, broccoli, and Brussels sprouts, etc. It is best known for promotion of coagulation and bone health.
Epidemiological studies focusing vitamin K in reduced risk and treatment of asthma have been inconclusive(a)(b)(c).

Menaquinone (vitamin K2), a variant of vitamin K, in a double blind study of 191 patients with bronchial asthma, showed an effective rate of 90.9% in mild patients, 86.7% in moderate patients, and 72.7% in severe patients(1). Other researchers suggested that treatment of menaquinone for long periods in patients with bronchial asthma indicated a significant inhibition of the disease(2). The data base of PubMed showed limitation in quantity of the research, we, therefore make no conclusion of the effectiveness of the vitamin in reduced risk and treatment of asthma. Overdoses can induce symptoms of Skin rash, Diarrhea, Nausea, Vomiting, Anemia, etc. Please make sure you follow the guideline of the Institute of Medicine of the National Academies.

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References
(a) Maternal intake of vitamins A, E and K in pregnancy and child allergic disease: a longitudinal study from the Danish National Birth Cohort by Maslova E, Hansen S, Strøm M, Halldorsson TI, Olsen SF.(PubMed)
(b) Fat-soluble vitamins and atopic disease: what is the evidence? by Litonjua AA.(PubMed)
(c) [Antioxidant and fat intake in patients with polinic asthma].[Article in Spanish] by de Luis DA1, Izaola O, Aller R, Armentia A, Cuéllar L.(PubMed)
(1) Menaquinone (vitamin K2) therapy for bronchial asthma. II. Clinical effect of menaquinone on bronchial asthma by Kimur I, Tanizaki Y, Sato S, Saito K, Takahashi K.(PubMed)
(2) Menaquinone (vitamin K2) therapy for bronchial asthma. I. Mechanism of action menaquinone on allergic reactions by Kimura I, Tanizaki Y, Sato S, Saito K, Takahashi K.(PubMed)

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Asthma in Vitamin E points of view

By Kyle J. Norton

The widespread of incidence of asthma over large 20 years in South East Asian population, specially in children and aging group has caused some concerns to the government and scientific community. It may be due to over intake in artificial ingredients, polluted environment as well as intake foods triggering the inflammatory allergens.
Vitamin E, a fat soluble vitamin, consisting eight different variants (alpha-, beta-, gamma-, and delta-tocopherol and alpha-, beta-, gamma-, and delta-tocotrienol) with varying levels of biological activity(2), found abundantly in corn oil, soybean oil, margarine, wheat germ oil, sunflower,safflower oils, etc. plays an important role in neurological functions and inhibition of platelet aggregation, regulation of enzymatic activity, free radical scavenger, etc..
General consensus suggestion of increased dietary vitamin E intake is associated with a reduced incidence of asthma, due its antioxidant status, but epidemiological studeies, linking vitamin E inreduced risk and treatment of asthma have not been conclusive(a)(b)(c)(d)(e).

1. Serum levels of vitamin E
Serum levels of vitamin in asthmatic patients may be correlated to the occurrence of the diseases. The University of Tampere study of in five European rural settings with Children of 1133 mothers recruited during pregnancy, showed no associated of with allergies or asthma by 6 years of age regardless the concentration of vitamin E(1). and the study of the Yamaguchi University, also indicated no correlation of levels of vitamin E and asthma in the a total of Of 2796 students attending schools in Shunan, Japan, in 2006.(1a). The University of Medical Sciences study indicated other wise as treatment of fluticasone and vitamin E (50mg/day) showed an significantly increased of Serum level of Vitamin E, with improved FEV1 and FEV1/FVC ratio(2). The study of acute asthmatic attack in children, showed a high degree of reactive oxygen species formation causing considerable oxidative stress with the high level of oxidants Serum malondialdehyde (MDA) and low level of antioxidants(vitamin C, vitamin E and uric acid)(3). Researchers at the Oslo University Hospital, in the study of children of 7-12 yr with asthma (n = 50) and no asthma (controls) (n = 52)indicated that schoolchildren with asthma and rhinitis had reduced levels of the major serum antioxidant albumin, and poorly controlled asthma was associated with decreased vitamin E and transferrin levels(4).

2. The effects
The Northwestern University study indicated the opposing regulatory effects as allergic inflammation is inhibited by supplementation with the purified natural vitamin E isoform α-tocopherol but elevated by the isoform γ-tocopherol when administered at physiological tissue concentrations(5)(6). But according to University of North Carolina School of Medicine, γ-tocopherol (GT) significantly decreased (p < 0.05) internalization of attached zymosan bioparticles and macrophage expression of CD206, CD36 and CD86 in allergic asthmatics through downregulation of both innate and adaptive immune response elements, and atopic status(7). The composition containing 623 mg of gamma-tocopherol, 61.1 mg of d-alpha-tocopherol, 11.1 mg of d-beta-tocopherol (11.1 mg), and 231 mg of d-sigma-tocopherol capsule in Phase I human dosing study showed the decreased systemic oxidative stress, increased serum levels of gamma-tocopherol, and inhibited monocyte responses to LPS without any adverse health effects(8). In Ovalbumin (OVA)-sensitized Brown Norway rats, treatment of gamma-tocopherol (gammaT), inhibited the pathogenesis of both AR and asthma inflammatory pathways(9). Suggestion of oxidant stress and diminished antioxidant defenses may be a cause of asthmatic disease(10) and uncontrolled asthma and severe asthma pattern have impaired antioxidant defences and are thus most susceptible to the damaging effects of oxidative stress(11). 1500 IU of natural-source d-α-tocopheryl acetate daily for at least 16 weeks in volunteered asthmatic patient, showed to inhibited oxidant stress, through modulation of allergic inflammation and airway hyperresponsiveness in human atopic asthmatics in vivo(12).

Taken altogether, Aγ-tocopherol, a variant of vitamin E, may be effective in reduced risk and treatment of asthmatic disorder, but further large sample and in multi centers studies are necessary to validate it claims. Over doses of vitamin E supplement can cause symptoms of blurred vision, weakness, dizziness, nausea, diarrhea, etc., please make sure you follow the guideline of the Institute of Medicine of the National Academies.

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References
(a) Vitamin E supplements in asthma: a parallel group randomised placebo controlled trial by Pearson PJ1, Lewis SA, Britton J, Fogarty A(PubMed)
(b) Effects of vitamin E on mitochondrial dysfunction and asthma features in an experimental allergic murine model by Mabalirajan U1, Aich J, Leishangthem GD, Sharma SK, Dinda AK, Ghosh B.(PubMed)
(c) Diet and asthma: vitamins and methyl donors by Han YY1, Blatter J1, Brehm JM1, Forno E1, Litonjua AA2, Celedón JC3.(PubMed)
(d) Asthma, allergy, and responses to methyl donor supplements and nutrients by Sharma S1, Litonjua A(PubMed)
(e) Vitamin e supplementation, lung functions and clinical manifestations in children with moderate asthma: a randomized double blind placebo- controlled trial by Ghaffari J1, Farid Hossiani R, Khalilian A, Nahanmoghadam N, Salehifar E, Rafatpanah H.(PubMed)
(1) Serum vitamin E concentrations at 1 year and risk of atopy, atopic dermatitis, wheezing, and asthma in childhood: the PASTURE study by Nwaru BI1, Virtanen SM, Alfthan G, Karvonen AM, Genuneit J, Lauener RP, Dalphin JC, Hyvärinen A, Pfefferle P, Riedler J, Weber J, Roduit C, Kaulek V, Braun-Fahrländer C, von Mutius E, Pekkanen J; PASTURE study group.(PubMed)
(1a) Association of serum carotenoids and tocopherols with atopic diseases in Japanese children and adolescents by Okuda M1, Bando N, Terao J, Sasaki S, Sugiyama S, Kunitsugu I, Hobara T.(PubMed)
(2) Vitamin e supplementation, lung functions and clinical manifestations in children with moderate asthma: a randomized double blind placebo- controlled trial by Ghaffari J1, Farid Hossiani R, Khalilian A, Nahanmoghadam N, Salehifar E, Rafatpanah H.(PubMed)
(3) Antioxidant status in acute asthmatic attack in children by Al-Abdulla NO1, Al Naama LM, Hassan MK.(PubMed)
(4) Altered oxidative state in schoolchildren with asthma and allergic rhinitis by Bakkeheim E1, Mowinckel P, Carlsen KH, Burney P, Carlsen KC.(PubMed)
(5) Vitamin E isoforms as modulators of lung inflammation by Abdala-Valencia H1, Berdnikovs S, Cook-Mills JM.(PubMed)
(6) Two faces of vitamin E in the lung by Cook-Mills JM1, Abdala-Valencia H, Hartert T.(PubMed)
(7) Effects of ex vivo γ-tocopherol on airway macrophage function in healthy and mild allergic asthmatics by Geiser M1, Lay JC, Bennett WD, Zhou H, Wang X, Peden DB, Alexis NE.(PubMed)
(8) In vivo gamma-tocopherol supplementation decreases systemic oxidative stress and cytokine responses of human monocytes in normal and asthmatic subjects by Wiser J1, Alexis NE, Jiang Q, Wu W, Robinette C, Roubey R, Peden DB.(PubMed)
(9) Gamma-tocopherol prevents airway eosinophilia and mucous cell hyperplasia in experimentally induced allergic rhinitis and asthma by Wagner JG1, Jiang Q, Harkema JR, Ames BN, Illek B, Roubey RA, Peden DB.(PubMed)
(10) Oxidative stress and antioxidant status in Saudi asthmatic patients by Al-Afaleg NO1, Al-Senaidy A, El-Ansary A.(PubMed)
(11) Reduced circulating antioxidant defences are associated with airway hyper-responsiveness, poor control and severe disease pattern in asthma by Wood LG1, Gibson PG.(PubMed)
(12) Natural-source d-α-tocopheryl acetate inhibits oxidant stress and modulates atopic asthma in humans in vivo by Hoskins A1, Roberts JL 2nd, Milne G, Choi L, Dworski R.(PubMed)

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Asthma in Vitamin D points of view

By Kyle J. Norton

The widespread of incidence of asthma over large 20 years in South East Asian population, specially in children and aging group has caused some concerns to the government and scientific community. It may be due to over intake in artificial ingredients, polluted environment as well as intake foods triggering the inflammatory allergens.
Vitamin D is a fat-soluble secosteroids found in small amount in few foods, including salmon, mackerel, sardines and tuna. The vitamin plays an important role in modulation of cellular proliferation, apoptosis induction, tumor growth suppression and promotion in absorption of minerals, including calcium, iron, magnesium, phosphate and zinc.

1. Serum of vitamin D
Epidemiological studies, linking the levels of serum 25-OH vitamin D with asthma may be inconclusive. The study of included 4,999 adults aged 30-60 years in 1999-2001. 3,032 of those included at baseline also participated at a follow-up examination 5 years later and 3,727 answered a 10 year follow-up questionnaire, showed no association of serum serum 25-OH vitamin D and the risk of asthma in Danish adults(1)(1a). Some researchers in the study of general Korean population suggested that vitamin D-insufficiency may have an increased likelihood of atopic dermatitis, but not asthma, allergic rhinitis, or IgE sensitization(2)(2a). But the study by Royal Brompton Hospital, London indicated otherwise in the study of relationships between serum vitamin D, lung function, and pathology in children with severe, therapy-resistant asthma (STRA)(3)(4) and 25 hydroxy vitamin D insufficiency is associated with bronchial asthma(4a) On the other hand, the study of iMayo Clinic indicated the correlation between serum 25(OH)D concentrations and positive pneumococcal antibody levels in all subjects regardless of asthma(5).

2. The benefits
According to the study by Universitätsmedizin Berlin, oral administration of vitamin D in vitamin D deficiency induced asthma, showed an increased expression of CD38 on B cells and a decreased T-cell-dependent proinflammatory cytokine production in doses of(6). In support to above study, Vitamin D found to decreaed inflammatory cytokine production from T-cell subsets implicated in asthma, according to Florida Atlantic University(7). In patient with in patients with steroid-resistant (SR) and steroid-sensitive (SS) asthma, oral administration of vitamin D, although exerted its anti-inflammatory and corticosteroid-enhancing effects in monocytes of patients with SR asthma and patients with SS asthma, the responses to corticosteroids in patients with SR asthma remained significantly lower than those in patients with SS asthma(8). Other in the study of the effect of vitamin D in severe therapy-resistant asthma (STRA) patients, showed an positive effect of 1α,25-dihydroxyvitamin D3, the active form of vitamin D in culture enhanced dexamethasone-induced IL-10 (Defective IL-10 expression causes a significantly diminished levels of anti-inflammatory interleukin (IL)-10))without marked effects on IL-13 or IL-17A production(9). Patients with severe asthma exhibited increased levels of TH17 cytokines.The study of King’s College London, also suggested that 1,25(OH)2D3 inhibits TH17 cytokine production in all patients with moderate-to-severe asthma(10), enhances the frequency of Treg cells(11)and upregulates CD200 on peripheral human CD4+ T cells(12).

Taking altogether, without going into reviews, vitamin D used conjunction with other anti asthma medicine and its the active form 1α,25-dihydroxyvitamin D3, may be associated to reduced risk and treatment of asthmatic diseases. Over doses of vitamin D supplement may cause excessive calcium absorption, calcification, Urinary stones etc. please make sure to follow the guideline of the Institute of Medicine of the National Academies.

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References
(1) The association of serum 25-OH vitamin D with atopy, asthma, and lung function in a prospective study of Danish adults by Thuesen BH1, Skaaby T, Husemoen LL, Fenger M, Jørgensen T, Linneberg A.(PubMed)
(1a) Vitamin d in pediatric inpatients with respiratory illnesses by Iqbal S1, Mosenkis EV, Jain P, Wiles A, Lerner J, Benton AS, Chamberlain JM, Freishtat RJ, Teach SJ.(PubMed)
(2) Low vitamin D levels are associated with atopic dermatitis, but not allergic rhinitis, asthma, or IgE sensitization, in the adult Korean population by Cheng HM1, Kim S2, Park GH3, Chang SE4, Bang S5, Won CH4, Lee MW4, Choi JH4, Moon KC(PubMed)
(2a) Vitamin D with asthma and COPD: not a false hope? A systematic review and meta-analysis By Zhang LL1, Gong J2, Liu CT3.(PubMed)
(3) Childhood asthma and vitamin D deficiency in Turkey: is there cause and effect relationship between them? Uysalol M1, Mutlu LC, Saracoglu GV, Karasu E, Guzel S, Kayaoglu S, Uzel N.(PubMed)
(4) Relationship between serum vitamin D, disease severity, and airway remodeling in children with asthma by Gupta A1, Sjoukes A, Richards D, Banya W, Hawrylowicz C, Bush A, Saglani S.(PubMed)
(4a) Serum 25 Hydroxy Vitamin D Insufficiency Associated with Bronchial Asthma in Lucknow, India by Awasthi S1, Vikram K.(PubMed)
(5) Serum 25-hydroxyvitamin D is associated with enhanced pneumococcal antibody levels in individuals with asthma by Lee J1, Zhao H, Fenta Y, Kita H, Kumar R, Juhn YJ.(PubMed)
(6) Oral vitamin D increases the frequencies of CD38+ human B cells and ameliorates IL-17-producing T cells by Drozdenko G1, Heine G, Worm M.(PubMed)
(7) Effect of vitamin D on T-helper type 9 polarized human memory cells in chronic persistent asthma by Keating P1, Munim A2, Hartmann JX2.(PubMed)
(8) Anti-inflammatory and corticosteroid-enhancing actions of vitamin D in monocytes of patients with steroid-resistant and those with steroid-sensitive asthma by Zhang Y1, Leung DY2, Goleva E3.(PubMed)
(9) Defective IL-10 expression and in vitro steroid-induced IL-17A in paediatric severe therapy-resistant asthma by Gupta A1, Dimeloe S, Richards DF, Chambers ES, Black C, Urry Z, Ryanna K, Xystrakis E, Bush A, Saglani S, Hawrylowicz CM.(PubMed)
(10) Enhanced production of IL-17A in patients with severe asthma is inhibited by 1α,25-dihydroxyvitamin D3 in a glucocorticoid-independent fashion by Nanzer AM1, Chambers ES, Ryanna K, Richards DF, Black C, Timms PM, Martineau AR, Griffiths CJ, Corrigan CJ, Hawrylowicz CM.(PubMed)
(11) The role of 1α,25-dihydroxyvitamin D3 and cytokines in the promotion of distinct Foxp3+ and IL-10+ CD4+ T cells by Urry Z1, Chambers ES, Xystrakis E, Dimeloe S, Richards DF, Gabryšová L, Christensen J, Gupta A, Saglani S, Bush A, O’Garra A, Brown Z, Hawrylowicz CM.(PubMed)
(12) 1α,25-dihydroxyvitamin D3 promotes CD200 expression by human peripheral and airway-resident T cells by Dimeloe S1, Richards DF, Urry ZL, Gupta A, Stratigou V, Farooque S, Saglani S, Bush A, Hawrylowicz CM.(PubMed)

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Asthma in Vitamin C points of view

The widespread of incidence of asthma over large 20 years in South East Asian population, specially in children and aging group has caused some concerns to the government and scientific community. It may be due to over intake in artificial ingredients and polluted environment.
Vitamin C, also known as L-ascorbic acid, is a water-soluble vitamin, found in fresh fruits, berries and green vegetables. It is best known for its free radical scavengers activity and regenerating oxidized vitamin E for immune support.
Epidemiological studies, linking vitamin C in reduced risk and treatment of asthma have been inconclusive(a)(b)(c)(d).

The study of the effects of antioxidant nutritional status with allergic rhinitis (AR) in Korean schoolchildren aged 6-12 years, in a total of 4,554 children in Seoul, Korea, showed a positive effect of Vitamin C intake negatively associated with an increased risk of AR symptoms(1). Accordin got the Rabin Medical Center, vitamin C also enhanced the protective effect on the hyperreactive airways of patients with exercise-induced asthma (EIA)(2). Oxidative stress mediated by reactive oxygen species is known to contribute to the inflammatory process of bronchial asthma. According to Dr. Ruprai RK., in the study of the oxidative stress plasma malondialdehyde and ascorbic acid (Vitamin C) showed an oxidative imbalance in asthmatic patients and antioxidant supply may have a beneficial impact on the free radical induced injury and improvement of respiratory reserve in Asthmatics(3)(4). In Saudi asthmatic patients, King Saud University study showed to exhibit oxidative stress and defective antioxidant status and suggested these may be primary causative factor in the pathogenesis of asthma(5).
In mega doses, vitamin C in asthmatic patients also Vitamin C decreased airway hyperreactivity to methacholine, inflammatory cell numbers in brochoalveolar lavage fluid, and moderate reduction of perivascular and peribronchiolar inflammatory cell infiltration(6).

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References
(a) Vitamin C supplementation for asthma by Kaur B1, Rowe BH, Arnold E.(PubMed)
(b) Vitamin C supplementation for asthma by Ram FS1, Rowe BH, Kaur B(PubMed)
(c) Vitamin C for asthma and exercise-induced bronchoconstriction by Milan SJ1, Hart A, Wilkinson M.(PubMed)
(d) Vitamin C and common cold-induced asthma: a systematic review and statistical analysis by Hemilä H.(PubMed)
(1) Association of antioxidants with allergic rhinitis in children from seoul by Seo JH1, Kwon SO, Lee SY, Kim HY, Kwon JW, Kim BJ, Yu J, Kim HB, Kim WK, Jang GC, Song DJ, Shim JY, Oh SY, Hong SJ.(PubMed)
(2) Blocking effect of vitamin C in exercise-induced asthma by Cohen HA1, Neuman I, Nahum H.(PubMed)
(3) Plasma oxidant-antioxidants status in asthma and its correlation with pulmonary function tests by Ruprai RK.(PubMed)
(4) Antioxidant status in acute asthmatic attack in children by Al-Abdulla NO1, Al Naama LM, Hassan MK.(PubMed)
(5) Oxidative stress and antioxidant status in Saudi asthmatic patients by Al-Afaleg NO1, Al-Senaidy A, El-Ansary A.(PubMed)
(6) Mega-dose vitamin C attenuated lung inflammation in mouse asthma model by Jeong YJ1, Kim JH, Kang JS, Lee WJ, Hwang YI.(PubMed)

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Asthma in Vitamin A points of view

Kyle J. Norton

The widespread of incidence of asthma over last 20 years in South East Asian population, specially in children and aging group has caused some concerns to the government and scientific community. It may be due to over intake in artificial ingredients and polluted environment.
Vitamin A is a general term of Vitamin A Retinol, retinal, beta-carotene, alpha-carotene, gamma-carotene, and beta-cryptoxanthin best known for its functions for vision health and antioxidant scavenger and essential for growth and differentiation of a number of cells and tissues.
Recommended intakes of vitamin A, according to the Institute of Medicine of the National Academies (formerly National Academy of Sciences) is 600 µg daily as extremely high doses (>9000 mg) can be toxicity as causes of dry, scaly skin, fatigue, nausea, loss of appetite, bone and joint pains, headaches, etc.
Epidemiological studies linking vitamin A in reduced risk and treatment of asthma have been inconclusive(a)(b)(c)(d)(e), but according to the University G. D’Annunzio, and Respiratory Pathophysiology Center, dietary supplementation or adequate intake of lycopene and vitamin A rich foods may be beneficial in asthmatic subjects(f).

1. Retinols
Serum vitamin A concentrations was found significantly lower in asthmatic subjects than healthy control subjects and administration of all-trans retinoic acid, ATRA dramatically attenuated airway inflammation through inhibiting Th2 and Th17 differentiation and/or functions. according to the Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine(1). ORMDL3 is a candidate gene of childhood onset asthma, and high-transcript of ORMDL3 is associated with the development of asthma. According to Nanjing Medical University, all-trans retinoic acid (ATRA) is an active metabolite of Vitamin A, reduced the risk of asthma through maintained airway epithelial integrity, inhibited asthma effector cells differentiation, modulating immune response, possibly via facilitates ORMDL3 production probable through PKA/CREB(2). Also in all-trans retinoic acid, ATRA, the Tehran University of Medical Sciences study suggested that ATRA diverted the human immune response in neutral conditions (without adding polarizing cytokines) by increasing FOXP3+ cells and decreasing RORγt+ cells(3). In rats with asthma, ATRA was found to alleviate airway hyperresponsiveness and airway remodeling possibly through decreasing the protein expression of MMP-9(4). The study at 1Inserm U700 and Université Paris 7, in a mouse model of ovalbumin (OVA)-induced T helper (Th) 2-type responses and airway remodeling, indicated a effectiveness of liposomally encapsulated ATRA (Lipo-ATRA) in exacerbates allergic immune and inflammatory responses, most likely through promoting Th2 development(5).
Unfortunately, according to Johns Hopkins University, even though animal models suggest that vitamin A deficiency affects lung development adversely and promotes airway hyperresponsiveness, and may predispose to an increased risk of asthma, but vitamin A supplementation early in life was not associated with a decreased risk of asthma in an area with chronic vitamin A deficiency(6).

2. Carotenoids (beta-carotene, alpha-carotene, gamma-carotene and beta-cryptoxanthin) Carotenoids, plant pigments, converted to vitamin A after intake, play an important role in prevention and treatment of some diseases through it antioxidant effects. In the study of the effect of vitamin intake among asthmatic subject, researchers at the Hung Kuang University, found that nutritional supplement therapy including beta carotene may improve dysregulated oxidant and antioxidant status, inflammation and immune responses, pulmonary function, and health-related quality of life in patients with mild to moderate allergic asthma(7). The John Hunter Hospital study of asthmatic subjects with airway hyper-responsiveness (AHR), indicated a reduced levels of beta-carotene and alpha-tocopherol compared with those without AHR, possibly due to impaired antioxidant defences and are thus most susceptible to the damaging effects of oxidative (8). Other researchers suggested that the imbalance of antioxidants found in asthmatic patients may be the possible causes of the disease(9) and modifying the dietary intake of carotenoids alters clinical asthma outcomes with improvements evident only through increased whole foods intake, not supplements(10)
But according to the study of Yamaguchi University, there was no significant association for asthma in Japanese youth(11) and the study of a total of 423 children from a rural area of Thailand, in a Health Interview for Asthma Control questionnaire, showed no correlation of dietary intake of carotenoids between asthmatic and non-asthmatic children(12).

Taken altogether, using vitamin A in prevention and treatment of asthmatic patient remains controversial. According to the study in summarization of the important of vitamin A in treatment of asthma, excessive intake of vitamin A may increase the risk or severity of asthma in industrialized countries whereas vitamin A deficiency continues to increase mortality from infectious diseases in developing countries(12).
But study summarized the important of vitamin A in treatment of asthma suggested that excessive intake of vitamin A may increase the risk or severity of asthma in industrialized countries whereas vitamin A deficiency continues to increase mortality from infectious diseases in developing countries(13). Overdoses can lead to toxic symptoms. Please make sure you follow the guideline of the Institute of Medicine of the National Academies.

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References
(a) Diet and asthma: vitamins and methyl donors by Han YY1, Blatter J1, Brehm JM1, Forno E1, Litonjua AA2, Celedón JC3.(PubMed)
(b) Maternal intake of vitamins A, E and K in pregnancy and child allergic disease: a longitudinal study from the Danish National Birth Cohort by Maslova E, Hansen S, Strøm M, Halldorsson TI, Olsen SF.(PubMed)
(c) Nutritional supplements and plasma antioxidants in childhood asthma by Fabian E1, Pölöskey P, Kósa L, Elmadfa I, Réthy LA.(PubMed)
(d) Nutritional supplement therapy improves oxidative stress, immune response, pulmonary function, and quality of life in allergic asthma patients: an open-label pilot study by Guo CH1, Liu PJ, Lin KP, Chen PC(PubMed)
(e) Cod liver oil intake and incidence of asthma in Norwegian adults–the HUNT study by Mai XM1, Langhammer A, Chen Y, Camargo CA Jr.(PubMed)
(f) Plasma lycopene and antioxidant vitamins in asthma: the PLAVA study by Riccioni G1, Bucciarelli T, Mancini B, Di Ilio C, Della Vecchia R, D’Orazio N.(PubMed)
(1) All-trans retinoic acid attenuates airway inflammation by inhibiting Th2 and Th17 response in experimental allergic asthma by Wu J1, Zhang Y, Liu Q, Zhong W, Xia Z.(PubMed)
(2) All-trans retinoic acid modulates ORMDL3 expression via transcriptional regulation by Zhuang LL1, Huang BX, Feng J, Zhu LH, Jin R, Qiu LZ, Zhou GP.(PubMed)
(3) Effect of all-trans retinoic acid (ATRA) on viability, proliferation, activation and lineage-specific transcription factors of CD4+ T cells by Bidad K1, Salehi E, Oraei M, Saboor-Yaraghi AA, Nicknam MH.(PubMed)
(4) [Effects of all-trans retinoic acid on airway responsiveness and airway remodeling in rats with asthma].[Article in Chinese] by Li WK1, Li Y, Zhong LL.(PubMed)
(5) Liposomal retinoic acids modulate asthma manifestations in mice by Maret M1, Ruffie C, Periquet B, Campo AM, Menevret M, Phelep A, Dziewiszek K, Druilhe A, Pretolani M.(PubMed)
(6) Supplementation with vitamin A early in life and subsequent risk of asthma by Checkley W1, West KP Jr, Wise RA, Wu L, LeClerq SC, Khatry S, Katz J, Christian P, Tielsch JM, Sommer A.(PubMed)
(7) Nutritional supplement therapy improves oxidative stress, immune response, pulmonary function, and quality of life in allergic asthma patients: an open-label pilot study by Guo CH1, Liu PJ, Lin KP, Chen PC.(PubMed)
(8) Reduced circulating antioxidant defences are associated with airway hyper-responsiveness, poor control and severe disease pattern in asthma by Wood LG1, Gibson PG.(PubMed)
(9) Antioxidants, oxidative stress, and pulmonary function in individuals diagnosed with asthma or COPD by Ochs-Balcom HM1, Grant BJ, Muti P, Sempos CT, Freudenheim JL, Browne RW, McCann SE, Trevisan M, Cassano PA, Iacoviello L, Schünemann HJ.(PubMed)
(10) Manipulating antioxidant intake in asthma: a randomized controlled trial by Wood LG1, Garg ML, Smart JM, Scott HA, Barker D, Gibson PG.(PubMed)
(11) Association of serum carotenoids and tocopherols with atopic diseases in Japanese children and adolescents by Okuda M1, Bando N, Terao J, Sasaki S, Sugiyama S, Kunitsugu I, Hobara T.(PubMed)
(12) Carotenoid intake and asthma prevalence in Thai children by Rerksuppaphol S1, Rerksuppaphol L.(PubMed)
(13) Vitamin A deficiency decreases and high dietary vitamin A increases disease severity in the mouse model of asthma by Schuster GU1, Kenyon NJ, Stephensen CB.(PubMed)

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Skin Lightening (Whitening) in Herbs, Foods and Antioxidants Points of View

Kyle J. Norton

Human skin pigmentation is the result of natural selection evolved to prevent damage to skin through regulation of ultraviolet radiated penetration depending to the production of melanin in the skin cells.
1. Hypo-pigment
a. Vitiligo is defined as a condition of destruction of cells that give your skin its color, causing white patches on your skin.
b. Albinism is a congenital disorder causes of complete or partial absence of pigment in the skin, hair and eyes as a result of restriction of the skin cells from producing melanin
2.Hyper pigment is a result of over production of pigments of certain cells in the skin, causing skin darkening in some area, such as tan or brown patches, commonly on the facial skin
3. Skin discoloring is a result of discoloring your skin in specific spots or very widespread
4. Chloasma is the appearance of brown patches of pigmentation on the forehead, cheeks, and neck
due to hormonal change during pregnancy.
5. Melasma happens to women who have fluctuation of hormones, are taking birth control pills and certain medications. with brownish-grayish patches on the skin, most often on the cheek.
Epidemiological studies, linking herbal medicine in skin lighting may have produced certain interest results(a)(b)(c).

A. The herbs
1. Ampelopsis japonica (Bai Lian)
Bai Lian is also known as Japanese Ampelopsis Root, the bitter, sweet, acrid and cool herb has been used in TCM to redice infection and to treat carbuncles, sores, scalding injuries, dysentery with blood, intestine pain, hemorrhoids as it clears Heat, expels toxins, resolves ulcers, promotes muscle regeneration, etc, by promoting the function of liver channel.
Ampelopsis japonica may process the property in treating skin hyperpigmentation disorders, such as melisma. According to the study at the Macao Polytechnic Institute, Linderagalactone c and (+)-n-methyllaurotetanine found in Ampelopsis japonica exhibited the strongest prospects in topical formulations, throguh high predicted tyrosinase binding scores and displayed good skin permeation properties in Surflex-Dock and the QSAR-based Dermal Permeability Coefficient Program (DERMWIN) and Skin Irritation Corrosion Rules Estimation Tool (SICRET) implemented in Toxtree.(1). The screening of 50 extracts from traditional Chinese medicines (TCM) used for tyrosinase activity-inhibiting agents, Ampelopsis japonica showed similar or greater ratio of cell growth IC(50) to cellular tyrosinase IC(50) when compared with other herbs(2).

2. Ginkgo biloba
Ginkgo biloba is oldest living tree species, genus Ginkgo, belonging to the family Ginkgoaceae, native to China, from temperate zone to subtropical zone and some parts of north America. It Has been used in traditional herbal medicine in treating impotence, memory loss,respiratory diseases, circulatory disorders and deafness as well as preventing drunkenness, and bedwetting.
Ginkgo biloba, one of the potent herb showed more advanced binding energies than the gold standard whitening agents, arbutin and kojic acid(1). Glycol extracts of ginkgo boiloba(F1A+M), may process of arbutin diffusion from the produced hydrogel formulations. According to Uniwersytet Medyczny w Łodzi, formulation containing glycol extract of ginkgo processed the most effective in arbutin release to the acceptor fluid through a semipermeable membrane (3). Other herbal extracts were also found to have a similar effect in promoting the process of arbutin release, including rosemary, sage and nettle(4).

3. Spicebush Root (Wu Yao)
Wu Yao is also known as Spicebush Root. The acrid and warm herb has been used in TCM as increased metabolism, antibiotic, anti-viral agent andto harmonize peristalsis of digestive tract, release intestinal gas, etc., as it moves Qi, warms the Kidneys. calms pain, etc. by enhancing the functions of lung, spleen, kidney and bladder.channels.
The study at Macao Polytechnic Institute, in the finding of herbal medicine used as tyrosinase inhibitors and for treatment of skin hyperpigmentation disorders, showed a promising result of
Spicebush Root’s chemical constituents in tyrosinase binding scores and displayed good skin permeation properties and minimal potential for skin sensitization and irritation(5). Other study at the Institute of Chinese Materia Medica of Shanghai University of Traditional Chinese Medicine, found that Spicebush Root consists appreciable antityrosinase activity with more than 50% inhibition against mushroom tyrosinase activity(6).

4. Chinese gall (Wu Bei zi)
Wu Bei Zi is also known as Chinese Gall. The sour, tart and cold herb has been used in TCM to treat chronic cough, chronic diarrhea with or without infection, spermatorrhea, night sweating, bleeding not during menses, etc., as it restrains Lungs, moves Fire downwards, strengthens the Intestines andthe Essence, prevents sweating, stops bleeding, etc. by enhancing the functions of lung, large intestine and kidney channels.
Chinese gall extract in the testing against mushroom tyrosinase activity inhibition, using ultraviolet A (UVA) or alpha-melanocyte-stimulating hormone (alpha-MSH) to stimulate B16 cells showed a promising effect in inhibition of melanin biosynthesis associated with hyperpigmentation in a dose-dependent manner, according to National Chiayi University(7). In Mouse melanocyte cell lines, water extract of Galla Chinensis, showed to exhibit higher depigmentation activity and caused lower tyrosinase activity(8).

5. Sargassum polycystum(Brown seaweed)
Sargassum polycystum, a type of brown seaweed, has been used for the treatment of skin-related disorders in traditional medicine. The ethanolic crude extract from Sargassum polycystum showed significant inhibition of melanogenesis through down activated cellular tyrosinase activity in B16F10 cells(9).

6. Nardostachys chinensis(Gan Song)
gan Song also known as Nardostachyos Root and Rhizome. The herb has been used in traditional Chinese medicine to treat melasma and lentigines, move Qi, calm pain, eliminate stagnation and invigorates the Spleen. According to Pusan National University, the active 20% methanol chromatographic fraction from the ethyl acetate layer (PPNC) showed to suppressed the melanin synthesis s, through stimulated MEK/ERK phosphorylation and PI3K/Akt signaling with suppressing cAMP levels and subsequently stimulating MITF and TRPs down-regulation(10).

7. Cuscuta japonica(Tu Si Zi)
Tu Si Zi is also known as Dodder Seed. The acrid, sweet and neutral herb has been used in TCM to treat psychological disorder, calm the fetus, prevent miscarriage, etc. as it tonifies kidneys, liver and spleen, improves yin, etc. by enhancing the functions of liver and kidney channels.
According to Pusan National University, the aqueous fraction from Semen cuscutae (AFSC) showed a marked reduction of melanin synthesis and tyrosinase activity in α-MSH-stimulated B16F10 cells through inhibited p38 MAPK phosphorylation with suppressed cAMP levels and subsequently down-regulate MITF and TRP expression(11).

8. Turmeric
Turmeric is a perennial plant in the genus Curcuma, belonging to the family Zingiberaceae, native to tropical South Asia. The herb has been used in trditional medicine as anti-oxidant, hypoglycemic, colorant, antiseptic, wound healing agent, and to treat flatulence, bloating, and appetite loss, ulcers, eczema, inflammations, etc.
Curcumin, a major chemical constituents of turmeric, showed to suppressed alpha-MSH-stimulated melanogenesis probably through involved the down-regulation of MITF and its downstream signal pathway through the activation of MEK/ERK or PI3K/Akt(12). Other sudy conducted by Pusan National University, also showed partial purification from C. longa (PPC) reduced melanin synthesis via MITF and its downstream signal pathway including tyrosinase and TRPs in alpha-MSH-induced melanogenesis, through activation of the MEK/ERK or Akt(13).

9. Fermenting red ginseng
Ginseng is a slow-growing perennial plants with fleshy roots, the genus Panax, belonging to the family Araliaceae. Depending to the climate where it grows, ginseng can be classified mainly into Panax ginseng Asian ginseng (root), Red ginseng(RG), wild ginseng, American ginseng (root).
Fermented red ginseng (FRG), increased contents of ginsenoside metabolites, such as Rg3, Rg5, Rk1, compound K, Rh1, F2, Rg2, and flavonoids content showed to increased anti-wrinkle efficacy, whitening efficacy, and reduced toxicological potency compared to RG(13a)

B. The foods
1. Long Yan (Longan)
Long Yan is also known as longan. The slightly sweet and neutral herb (fruit) has been used in TCM as notification after illnesses, neurasthenia, forgetfulness, palpitation, insomnia, etc. as it tonifies Heart and Spleen, benefits Qi and Blood, etc. Longan seeds containing high levels of polyphenolic compounds such as corilagin, gallic acid and ellagic acid, may be potential sources of potent natural dietary antioxidants in the application as a new natural skin-whitening agent(14), through its higher antioxidant and antityrosinase activities(15).

2. Green tea
Green tea contains more amount of antioxidants than any drinks or food with the same volume, and is the leaves of Camellia sinensis, undergone minimal oxidation during processing, originated from China. Green tea has been a precious drink in traditional Chinese culture and used exceptional in socialization for more than 4000 thousand years. Because of their health benefits, they have been cultivated for commercial purposes all over the world.
Green tea polyphenol may be used as a natural ingredient with excellent physiological functions for the human skin through cosmetic or food composition(16). Other study of the effects of tea polysaccharides (TPS) and polyphenols (TPP) on skin, showed to exhibit the moisture absorption and retention, sunscreen, promoting the proliferation of fibroblast cells, and tyrosinase inhibitory effect(17).

3. Cinnamon
Cinnamon is a spice derived from the inner bark of tree, native to South East Asia, of over 300 species of the genus Cinnamomum, belonging to the family Lauraceae.. The herb has been use in herbal and traditional medicine as anti-fungal and bacteria level to improve reproductive organ, prevent flatulence and intestinal cramping, treat indigestion, diarrhea, bad breath, headache, migraine, etc.
The essential oil extracted from Cinnamomum cassia Presl (CC-EO) and its major component, cinnamaldehyde, possess potent anti-tyrosinase and anti-melanogenic activities through theirs antioxidant activities and may be a potential source of skin-whitening agents(18)

4. Red Onion((Allium cepa)
The onion is a plants in the genus Allium, belongs to the family Alliaceae, a close relation of garlic. It It is often called the “king of vegetables” because of its pungent taste and found in a large number of recipes and preparations spanning almost the totality of the world’s cultures. Depending on the variety, an onion can be sharp, spicy, tangy, pungent, mild or sweet.
Quercetin 4′-O-β-D-glucopyranoside was isolated from the dried skin of A. cepa. showed tyrosinase inhibitory activity as it possesses ingredients with potential for skin-whitening cosmetics(19).

5. Ginger
Ginger (Zingiber officinale) or ginger root is the genus Zingiber, belonging to the family Zingiberaceae, native to Tamil. It has been used in traditional and Chinese medicine to treat dyspepsia, gastroparesis, constipation, edema, difficult urination, colic, etc.
[6]-Gingerol, an active component of ginger not only (25-100 µM) effectively suppressed murine tyrosinase activity and decreases the amount of melanin, but also decreased the intracellular reactive oxygen species (ROS) level in a dose-dependent manner(20). the University of Malaya, in the study of the effects of [8]-Gingerol, another active component of Zinger, found that [8]-gingerol (5-100μM) not only effectively suppressed intracellular tyrosinase activity and decreased the amount of melanin in B16F10 and B16F1 cells, but also fectively decreased intracellular reactive species (RS) and reactive oxygen species (ROS) levels at the same dose manner, probably through down-regulation of both mitogen-activated protein kinases (MAPK) and protein kinase A (PKA) signaling pathways or through its antioxidant properties(21).

6. Pomegranate
Pomegranates is a fruit-bearing small tree, genus Punica, belonging to family Lythraceae, native to Iran but has been cultivated in Asian since ancient time.
Pomegranate extract (PE) containing 90% ellagic acid administered orally, inhibited UV-induced skin pigmentation on the back of brownish guinea pigs with skin-whitening effect was similar between guinea pigs fed with PE and those fed with L-ascorbic acid(21a) and moderate effect in human skin(21b).

C. The Antioxidants
C.1. Free radical scavengers
Suggestions of antioxidants, may be next potential agent in inhibition of tyrosinase activity and reduction of the melanin content in cells(22)(22a)
1. Vitamin C,
Vitamin C also known as L-ascorbic acid, is a water-soluble vitamin, found in fresh fruits, berries and green vegetables. It is best known for its free radical scavengers activity and regenerating oxidized vitamin E for immune support.
Ascorbic acid (AA) has been well known as a skin whitening agent, according to the Mahidol University, AA showed to inhibit UVA-mediated catalase (CAT) inactivation, glutathione (GSH) depletion, oxidant formation and NO production through suppression of eNOS and iNOS mRNA via its antioxidant defense(23). In the comparison of orchid extracts and 3% vitamin C derivative formulated, researchers at the Osaka National Hospital, National Hospital Organizationfound that the orchid-rich plant extracts possess efficacy similar to vitamin C derivative in whitening the skin as well as melasma and lentigo senilis on the face of Japanese women(24). Other study suggested that topical application of the composition of L(+) lactic acid supplemented with ascorbic acid (1%) produced a whitening effect and a modest preferential lightening of age spots which becomes apparent after three months, through demonstrated clinically by the test panelists, and trained clinicians, and with objective instrumental methods(25).

2. Vitamin E
Vitamin E, a fat soluble vitamin, consisting eight different variants (alpha-, beta-, gamma-, and delta-tocopherol and alpha-, beta-, gamma-, and delta-tocotrienol) with varying levels of biological activity(26), found abundantly in corn oil, soybean oil, margarine, wheat germ oil, sunflower,safflower oils, etc. plays an important role in neurological functions and inhibition of platelet aggregation, regulation of enzymatic activity, free radical scavenger, etc..
The study in comparison of the effects of vitamin E analogues (d-alpha-, dl-alpha-, d-beta-, d-gamma-, and d-delta-tocopherols, d-alpha- and dl-alpha-tocopheryl acetates) and 2,2,5,7,8-pentamethyl-6-hydroxychroman (PMC) on melanogenesis in mouse B16 melanoma cells, showed a positive effects of d-beta-tocopherol and d-gamma-tocopherol, 2 variants of vitamin E, in skin whitening with lower skin toxicity, as well as improved skin pigmentation such as skin spots and freckles caused by UV exposure(27). According to Kobe University School of Medicine, alpha-Tocopheryl ferulate (alpha-TF), a compound containing alpha-T (a variant of vitamin E) and ferulic acid exhibited an efficient whitening effects, through suppressed melanogenesis and inhibited biological reactions induced by reactive oxygen species(28)(29).

C.2. The antioxidants
1. Resveratrol
Resveratrol is a phytochemical in the class of Stilbenoids, found abundantly in skins and seed of grape wine, nuts, peanuts, etc.
Piceatannol, a derivative of resveratrol exerted its antimelanogenic action through the combined effect of antioxidative property
and suppressed RS generation while increasing the GSH/GSSG ratio(30). According to 1Johnson &
Johnson Skin Research Center, resveratrol may be a potential cosmetic skin whitening agent through
reduced microphthalmia-associated transcription factor and tyrosinase promoter activities(31).

4. Glutathione
Glutathione (GSH), an antioxidants plays an important role in protecting cells against the free radicals
and ixidative stress, may be a potential agent in the management of hyperpigmentation(32). According
to the Chulalongkorn University, orally administered glutathione, 500 mg per day for 4 weeks, was found
effectively in reduced melanin indices consistently in all subjects(33) and may be used in the treatment
of pigmentary disorders.(34). Other study also indicated the effectiveness of glutathione in regulatesing
melanocytotoxicity and depigmenting potency of N-acetyl-4-S-CAP in black and yellow mice(35)

Taken altogether, although with scattered data, the herbs, foods, and antioxidants indicated above may potent in exhibition of the depigment and lightening (whitening) effects, through inhibited, and biological reactions induced by reactive oxygen species and suppressed melanogenesis and intracellular tyrosinase activity. As always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying.

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References
(a) Tyrosinase modulation by five Rwandese herbal medicines traditionally used for skin treatment by Kamagaju L1, Morandini R, Bizuru E, Nyetera P, Nduwayezu JB, Stévigny C, Ghanem G, Duez P.(PubMed)
(b) An ethnobotanical survey of medicinal plants used in Rwanda for voluntary depigmentation by Kamagaju L1, Bizuru E, Minani V, Morandini R, Stévigny C, Ghanem G, Duez P.(PubMed)
(c) Tyrosinase inhibition by extracts and constituents of Sideroxylon inerme L. stem bark, used in South Africa for skin lightening by Momtaz S1, Mapunya BM, Houghton PJ, Edgerly C, Hussein A, Naidoo S, Lall N.(PubMed))
(1) In silico prediction of the cosmetic whitening effects of naturally occurring lead compounds by Fong P1, Tong HH.(PubMed)
(2) Screening of Chinese herbal medicines for antityrosinase activity in a cell free system and B16 cells by Ye Y1, Chou GX, Mu DD, Wang H, Chu JH, Leung AK, Fong WF, Yu ZL(PubMed)
(3) [Glycol plant extracts in the prescription of topical skin-whitening hydrogels].[Article in Polish] by Piechota-Urbańska M1, Berner-Strzelczyk A.(PubMed)
(4) [The effect of dry standardized plant extracts on the process of arbutin release from topical preparations produced on Carbopol base].[Article in Polish] by Piechota-Urbańska M.(PubMed)
(5) In silico prediction of the cosmetic whitening effects of naturally occurring lead compounds by Fong P1, Tong HH.(PubMed)
(6) Screening of Chinese herbal medicines for antityrosinase activity in a cell free system and B16 cells by Ye Y1, Chou GX, Mu DD, Wang H, Chu JH, Leung AK, Fong WF, Yu ZL.(PubMed)
(7) Melanogenesis inhibition by gallotannins from Chinese galls in B16 mouse melanoma cells by Chen LG1, Chang WL, Lee CJ, Lee LT, Shih CM, Wang CC.(PubMed)
(8) Depigmentation of melanocytes by the treatment of extracts from traditional Chinese herbs: a cell culture assay by Zhong S1, Wu Y, Soo-Mi A, Zhao J, Wang K, Yang S, Jae-Ho Y, Zhu X.(PubMed)
(9) Inhibitory effects of Sargassum polycystum on tyrosinase activity and melanin formation in B16F10 murine melanoma cells by Chan YY1, Kim KH, Cheah SH(PubMed)
(10) Partially purified components of Nardostachys chinensis suppress melanin synthesis through ERK and Akt signaling pathway with cAMP down-regulation in B16F10 cells by Jang JY1, Kim HN, Kim YR, Choi WY, Choi YH, Shin HK, Choi BT.(PubMed)
(11) Aqueous fraction from Cuscuta japonica seed suppresses melanin synthesis through inhibition of the p38 mitogen-activated protein kinase signaling pathway in B16F10 cells by Jang JY1, Kim HN, Kim YR, Choi YH, Kim BW, Shin HK, Choi BT.(PubMed)
(12) Curcumin suppresses alpha-melanocyte stimulating hormone-stimulated melanogenesis in B16F10 cells by Lee JH1, Jang JY, Park C, Kim BW, Choi YH, Choi BT.(PubMed)
(13) Partially purified Curcuma longa inhibits alpha-melanocyte-stimulating hormone-stimulated melanogenesis through extracellular signal-regulated kinase or Akt activation-mediated signalling in B16F10 cells by Jang JY1, Lee JH, Jeong SY, Chung KT, Choi YH, Choi BT.(PubMed)
(13a) Fermenting red ginseng enhances its safety and efficacy as a novel skin care anti-aging ingredient: in vitro and animal study by Lee HS1, Kim MR, Park Y, Park HJ, Chang UJ, Kim SY, Suh HJ.(PubMed)
(14) Evaluation of free radical scavenging and antityrosinase activities of standardized longan fruit extract by Rangkadilok N1, Sitthimonchai S, Worasuttayangkurn L, Mahidol C, Ruchirawat M, Satayavivad J.(PubMed)
(15) Enhanced antioxidant and antityrosinase activities of longan fruit pericarp by ultra-high-pressure-assisted extraction by rasad KN1, Yang B, Shi J, Yu C, Zhao M, Xue S, Jiang Y.(PubMed)
(16) Physiological activity of irradiated green tea polyphenol on the human skin by An BJ1, Kwak JH, Son JH, Park JM, Lee JY, Park TS, Kim SY, Kim YS, Jo C, Byun MW.(PubMed)
(17) Protective effects of tea polysaccharides and polyphenols on skin by Wei X1, Liu Y, Xiao J, Wang Y.(PubMed)
(18) Cinnamomum cassia essential oil inhibits α-MSH-induced melanin production and oxidative stress in murine B16 melanoma cells by Chou ST1, Chang WL, Chang CT, Hsu SL, Lin YC, Shih Y.(PubMed)
(19) Tyrosinase inhibitory effect of quercetin 4′-O-β-D-glucopyranoside from dried skin of red onion (Allium cepa) by Arung ET1, Wijaya Kusuma I, Shimizu K, Kondo R.(PubMed)
(20) Inhibitory effect of [6]-gingerol on melanogenesis in B16F10 melanoma cells and a possible mechanism of action by Huang HC1, Chiu SH, Chang TM.(PubMed)
(21) [8]-Gingerol inhibits melanogenesis in murine melanoma cells through down-regulation of the MAPK and PKA signal pathways by Huang HC1, Chou YC, Wu CY, Chang TM.(PubMed)
(21a) Inhibitory effect of an ellagic acid-rich pomegranate extract on tyrosinase activity and ultraviolet-induced pigmentation by Yoshimura M1, Watanabe Y, Kasai K, Yamakoshi J, Koga T.(PubMed)
(21b) Effects of oral administration of ellagic acid-rich pomegranate extract on ultraviolet-induced pigmentation in the human skin by Kasai K1, Yoshimura M, Koga T, Arii M, Kawasaki S.(PubMed)
(22) Biofunctional Constituents from Liriodendron tulipifera with Antioxidants and Anti-Melanogenic Properties by Li WJ1, Lin YC, Wu PF, Wen ZH, Liu PL, Chen CY, Wang HM.(PubMed)
(22a) The effects of areca catechu L extract on anti-inflammation and anti-melanogenesis by Lee KK1, Choi JD.(PubMed)
(23) Inhibition of UVA-mediated melanogenesis by ascorbic acid through modulation of antioxidant defense and nitric oxide system by Panich U1, Tangsupa-a-nan V, Onkoksoong T, Kongtaphan K, Kasetsinsombat K, Akarasereenont P, Wongkajornsilp A.(PubMed)
(24) \Whitening efficacy of plant extracts including orchid extracts on Japanese female skin with melasma and lentigo senilis by Tadokoro T1, Bonté F, Archambault JC, Cauchard JH, Neveu M, Ozawa K, Noguchi F, Ikeda A, Nagamatsu M, Shinn S.(PubMed)
(25) The effects of topical l(+) lactic Acid and ascorbic Acid on skin whitening by Smith WP.(PubMed)
(26) Traber MG. Vitamin E. In: Shils ME, Shike M, Ross AC, Caballero B, Cousins R, eds. Modern Nutrition in Health and Disease. 10th ed. Baltimore, MD: Lippincott Williams & Wilkins, 2006;396-411.
(27) Comparison of the inhibitory effects of vitamin E analogues on melanogenesis in mouse B16 melanoma cells by Kamei Y1, Otsuka Y, Abe K.(PubMed)
(28) The depigmenting effect of alpha-tocopheryl ferulate on human melanoma cells by Funasaka Y1, Chakraborty AK, Komoto M, Ohashi A, Ichihashi M.(PubMed)
(29) Depigmenting effect of alpha-tocopheryl ferulate on normal human melanocytes by Funasaka Y1, Komoto M, Ichihashi M.(PubMed)
(30) Piceatannol inhibits melanogenesis by its antioxidative actions by Yokozawa T1, Kim YJ.(PubMed)
(31) Modulation of microphthalmia-associated transcription factor gene expression alters skin pigmentation by Lin CB1, Babiarz L, Liebel F, Roydon Price E, Kizoulis M, Gendimenico GJ, Fisher DE, Seiberg M.(PubMed)
(32) Natural ingredients for darker skin types: growing options for hyperpigmentation by Alexis AF Blackcloud P.(PubMed)
(33) Glutathione as an oral whitening agent: a randomized, double-blind, placebo-controlled study by Arjinpathana N1, Asawanonda P.(PubMed)
(34) Glutathione as a depigmenting agent: an overview by Villarama CD1, Maibach HI.(PubMed)
(35) Glutathione plays a key role in the depigmenting and melanocytotoxic action of N-acetyl-4-S-cysteaminylphenol in black and yellow hair follicles by Alena F1, Dixon W, Thomas P, Jimbow K.(PubMed)

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Asthma in Foods points of view

Respiratory Disease is defined as medical conditions which affect the breathing organ and tissues including Inflammatory lung disease, Obstructive lung diseases, Restrictive lung diseases, Respiratory tract infections, trachea, bronchi, bronchioles, alveoli, the nerves and muscles breathing , etc.
Asthma is a chronic inflammatory disease affecting the air way of the lung with recurring symptoms, such as wheezing, chest tightness, shortness of breath, and coughing. The disease affects people of all ages, and mostly starts during childhood. According to American academy, allergy, asthma and immunology, about 1 in 10 children (10%) had asthma and 1 in 12 adults (8%) had asthma in 2009. (about 25 million, or 8% of the U.S. population)(1).
Epidemiological studies, linking foods in reduced risk and treatment have not been conclusive(a)(b)(c)(d), but certain foods have been found to be effectively.

A. Types vegetable reduced risk of asthma
1. Garlic
Garlic (Allium sativum) is a species in the onion genus, belonging to family Amaryllidaceae, native to central Asia. It has been used popularly in traditional and Chinese medicine in treating common cold and flu to the Plague, blood pressure cholesterol levels, natural antibiotic, etc.
Diallyl disulfide (DADS), a major organosulfur compound found in garlic, in an ovalbumin-induced model of allergic asthma and RAW264.7 cells, showed to inhibit the proinflammatory proteins, through up regulation of Nrf-2/HO-1 and down regulation of NF-κB pathways(2). According to the study by Tarbiat Modares University, purified aged garlic extract exhibited the protective effect of asthma through a significant decrease in the hallmark criteria of allergic airway inflammation levels(3).

2. Tomatoes
Tomato is a red, edible fruit, genus Solanum, belongs to family Solanaceae, native to South America. Because of its health benefits, tomato is grown world wide for commercial purpose
and often in green house.
High-antioxidant diet is associated to reduced risk of asthma, according to University of Newcastle, whole foods intake such as tometoes showed to alter clinical asthma outcomes of patient who were in low antioxidant given tomato extract (45 mg lycopene/d)(4). The John Hunter Hospital study also supported the role of tomato juice and extract in reduced airway neutrophil influx with tomato extract also reduced sputum neutrophil elastase activity(5). Naringenin chalcone, the other polyphenols found in the skin of red tomatoes, showed to suppresses asthmatic symptoms through inhibition of Th2 cytokine production from CD4 T(6).

3. Seaweeds
Marine algae have been used as food products and herbal medicine in many countries throughout human history with an abundance of algae floral. In recent studies, marine algae may consist great sources of chemical ingredients in treating inflammatory and allergic disorders, such as such as asthma, atopic dermatitis, and allergic rhinitis (7)(8). According to the study at Pukyong National University, many marine macro- and microalgae have been reported to have potential to ameliorate the effect of asthma and further studies are needed to identify the molecular mechanism of this disease to apply those marine resources against asthma effectively(9). Iota-Carrageenan, derived from red seaweed showed to be potent against anti-rhinoviralas (HRVs may worsen COPD and asthma) its effectively prevents the replication of HRV1A, HRV2, HRV8, HRV14, HRV16, HRV83 and HRV84 in primary human nasal epithelial cells in culture(10).

4. Ginger
Ginger (Zingiber officinale) or ginger root is the genus Zingiber, belonging to the family Zingiberaceae, native to Tamil. It has been used in traditional and Chinese medicine to treat dyspepsia, gastroparesis, constipation, edema, difficult urination, colic, etc.
Purified components of ginger was found to be effective in relax airway smooth muscle (ASM), through involvement of PDE4D inhibition and cytoskeletal regulatory proteins. Together with other chemical constituents such as β-agonists, 6-gingerol, 8-gingerol, or 6-shogaol may augment existing asthma therapy, insisted by Columbia University study(11). Quercetin, a chemical compound found in ginger, relaxed airway smooth muscle via cAMP-mediated pathways and augments β-agonist relaxation(12). The Columbia University Medical Center study also found many ginger’s isolated active components, [6]-gingerol, [8]-gingerol, and [6]-shogaol, relax ASM, and [8]-gingerol attenuated airway hyperresponsiveness, in part by altering [Ca(2+)](i) regulation(13).

5. Broccoli
Broccoli is a mustard/cabbage plant, belong to the family Brassicaceae. It has large flower heads, usually green in color and the mass of flower heads is surrounded by leaves and evolved from a wild cabbage plant on the continent of Europe.
Sulforaphane, a major chemical compound found in broccoli sprout demonstrated the potential preventive and therapeutic potential of broccoli or broccoli sprouts rich in glucoraphanin for reducing the impact of particulate pollution on allergic disease and asthma, according to David Geffen School of Medicine at UCLA(14).In (OVA)-induced murine asthma model, Sulforaphane significantly alleviated the OVA-induced airway hyperresponsiveness possiblt through suppressed the increase in the levels of SOCS-3 and GATA-3 and IL-4 expression in the OVA-challenged mice(15).

6. Spinach
Spinach is an edible flowering plant in the genus Spinacia, belongs to the family of Amaranthaceae and native to central and southwestern Asia. It is considered as a healthy plant containing vary vitamins and minerals. aqueous extract of spinach, in ovalbumin-induced asthmatic model. exerted strong anti-asthmatic effects through induction of a decrease in the CD4+ cell number, IL-4/13, and other molecular markers in the lung(16).

B. Types of fruits reduced risk of asthma
1. Apple
Apple is the pomaceous fruit of the apple tree, a species of the rose family Rosaceae. It is one of the most widely cultivated tree fruits. The tree is originated in Central Asia. Drinking apple juice from concentrate at least once a day (compared with less than once a month) might be negatively associated with current wheeze (17a). According to the Cornell University, phenolics, flavonoids and carotenoids of apple may play a key role in reducing chronic disease risk, including asthma(17)(18)(19). The study at the King’s College London, showed a possibly protective effect of apple in reduced risk of apple with the presence of other flavonoids or polyphenols on obstructive lung disease, instead of catechins, flavonols and flavones(20). According to the Brigham and Women’s Hospital, Belladonna alkaloids, derived from the thorn-apple plant were used to treat asthma in 1905, and chemically synthesized entities in this class are still in use today(21).

2. Grape
Grape is a woody vines of the genus Vitis, belong to the family Vitaceae, native to southern Turkey.
Polyphenols found in Fermented Grape Marc (FGM) may be effective in exhibited several immunomodulating activities, including decreased oxidative burst of human polymorphonuclear cells and monocytes of which induced anti-allergic and anti inflammatory effects in chronic asthma(22). According to the study of Graduate School of Science, Kitasato University, Fermented Grape Marc (FGM) also suppressed both phases of type-I allergic responses, through a fraction extractable with acetone(23).

3. Strawberry
Strawberries is a genius of Fragaria × ananassa belongs to the family Roseaceae. They have been grown all over the world with suitable climate for commercial profits and for health benefits.
Gallic acid (3,4,5-trihydroxybenzoic acid), a polyphenyl natural products found abundantly in gallnut inhibited inflammatory allergic diseases, through blocking histamine release and pro-inflammatory cytokine expression(24). The Johannes Gutenberg University, also suggested that the composition of Gallic acid, methyl gallate and quercetin in animal study showed significant effects with with one certain fraction (GG II, 3 days, 3 x 2 mg/kg) in reduced allergen- and PAF-induced bronchial reactions by more than 70%(25).

C. Seed and Nut
1. Sesame oil
Sesame is a species of Sesamum indicum and belong to the family of Pedaliaceae, native to to sub-saharan Africa. The tree can grow to 1.6 to 3.3 ft tall and is mainly cultivated for their seeds. Sesame oil, a natural product with anti-inflammatory property showed to inhibited pulmonary edema and decreased interleukin (IL)-1 β and IL-6 levels in bronchoalveolar lavage fluid in OVA-treated mice through inhibition of systemic IgE level in allergic asthma(26).

2. Faxseed
Flax seed is native to the region of the eastern Mediterranean to India and also known as common flax or linseed. Flax is an erect annual plant, it can grow to 1.2 m tall. The leaves are 20–40 mm long and 3 mm broad. Suggestions of saturated and n-6 fatty acids and concomitant decrease in n-3 fatty acids may be a major driver of the increase in the incidence of inflammatory diseases such as asthma, allergy, and atherosclerosis. According to the Wake Forest University, dietary supplementation with flaxseed oil affects the biochemistry of fatty acid metabolism through the balance of proinflammatory mediators and atherogenic lipids, affecting the modulation of inflammatory diseases(27) and patients with asthma and allergic rhinitis may benefit from hydration and a diet low in sodium, omega-6 fatty acids, and transfatty acids, but high in omega-3 fatty acids (i.e., fish, almonds, walnuts, pumpkin, and flax seeds)(28).
3. Sunflower seed
Sunflower is a genus of Helianthus, belong to the family Asteraceae and native to the Americas. It grow to heights between 5–12 ft. Sunflower seeds are usually classified by the difference of their husks and are considered as healthy snack of a meal.
Helianthus annuus (Sunflower) seed (HAS) aqueous extract, may consist a potential in reducing the asthma-like symptoms induced by a mouse ovalbumin challenge model(29).

C. Others
1. Green Tea
Green tea contains more amount of antioxidants than any drinks or food with the same volume, and is the leaves of Camellia sinensis, undergone minimal oxidation during processing, originated from China. Green tea has been a precious drink in traditional Chinese culture and used exceptional in socialization for more than 4000 thousand years. Because of their health benefits, they have been cultivated for commercial purposes all over the world.
According to teh study at State University of New York Downstate Medical Center, green tea extract (GTE), and its major catechin, consisted an immunoregulatory effects through suppression of IgE production by peripheral blood mononuclear cells of allergic asthmatic patinets(30) and B cell production of IgE without inducing apoptosis(31). Other study suugested a anti asthmatic effect of aqueous extract of Camellia sinensis through increasing the expression level of tumor necrosis factor-beta and interferon-gamma and decreasing the expression of anti-asthmatic cytokines in the lung(32).

2. Fish and fish oil
Consumption of fish has also been related to lower airway hyperreactivity among children and higher lung function in adults, according to Pan American Health Organization and National Institute of Public Health(33) and fish oil supplements, administered in a dosage of 1 to 1.2 g of EPA and DHA per day, also may be helpful to some patients with asthma(34).According to Ewha Womans University, asthmatic patient were found to consume fewer amounts of kimchi and fish but had a higher cereal intake than those without asthma(35).

3. Whole grain
Wholegrain is cereal grains containing cereal germ, endosperm, and bran. According to the study by National Institute of Public Health and the Environment, intake of whole grain is associated to reduced risk asthma and may have a protective effect against asthma in children(36). Other study suggested that whole grain and high in fruits, vegetables, and low in alcohol and fatty foods may be useful for prevention of cardiovascular disease and cancer, to protect respiratory health in both children and adults(37).

4. Coffee
Coffee made from the roasted seeds of the genus Coffee, belonging to the family Rubiaceae native to southern Arabia. Strong evidence suggested that drinking coffee reduced risk of asthma. according to Istituto Centrale di Statistica, caffeine intake has a bronchodilator effect in asthma, and long-term moderate coffee consumption may not only reduce symptoms, but also prevent the clinical manifestation of bronchial asthma(38) and people who drank coffee on a regular basis had a 29% reduction in the odds of having current asthma(39). The University of London aslo suggested that caffeine appears to improve airways function modestly, for up to four hours, in people with asthma(40).

Taking altogether, some foods have been found effectively in reduced risk and treatment of asthma and allergic induced asthmatic disease. Further studies with large sample size and multi centers are necessary to identify the ingredients for improvement of validation. As always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying

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References
(1) American academy, allergy, asthma and immunology(AAAAI)
(a) Association between nutrition and the evolution of multimorbidity: The importance of fruits and vegetables and whole grain products by Ruel G1, Shi Z, Zhen S, Zuo H, Kröger E, Sirois C, Lévesque JF, Taylor AW.(PubMed)
(b) Dietary factors associated with lifetime asthma or hayfever diagnosis in Australian middle-aged and older adults: a cross-sectional study by Rosenkranz RR1, Rosenkranz SK, Neessen KJ.(PubMed)
(c) Protective effect of fruits, vegetables and the Mediterranean diet on asthma and allergies among children in Crete by Chatzi L1, Apostolaki G, Bibakis I, Skypala I, Bibaki-Liakou V, Tzanakis N, Kogevinas M, Cullinan P.(PubMed)
(d) Effect of diet on asthma and allergic sensitisation in the International Study on Allergies and Asthma in Childhood (ISAAC) Phase Two by Nagel G1, Weinmayr G, Kleiner A, Garcia-Marcos L, Strachan DP; ISAAC Phase Two Study Group.(PubMed)
(2) Diallyl-disulfide, an organosulfur compound of garlic, attenuates airway inflammation via activation of the Nrf-2/HO-1 pathway and NF-kappaB suppression by Shin IS1, Hong J, Jeon CM, Shin NR, Kwon OK, Kim HS, Kim JC, Oh SR, Ahn KS.(PubMed)
(3) Purified aged garlic extract modulates allergic airway inflammation in BALB/c mice by Zare A1, Farzaneh P, Pourpak Z, Zahedi F, Moin M, Shahabi S, Hassan ZM.(PubMed)
(4) Manipulating antioxidant intake in asthma: a randomized controlled trial by Wood LG1, Garg ML, Smart JM, Scott HA, Barker D, Gibson PG.(PubMed)
(5) Lycopene-rich treatments modify noneosinophilic airway inflammation in asthma: proof of concept by Wood LG1, Garg ML, Powell H, Gibson PG.(PubMed)
(6) Naringenin chalcone suppresses allergic asthma by inhibiting the type-2 function of CD4 T cells by Iwamura C1, Shinoda K, Yoshimura M, Watanabe Y, Obata A, Nakayama T.(PubMed)
(7) Potential targets for anti-inflammatory and anti-allergic activities of marine algae: an overview BY Vo TS1, Ngo DH, Kim SK.(PubMed)
(8) Antiallergic benefit of marine algae in medicinal foods by Kim SK1, Vo TS, Ngo DH.(PubMed)
(9) Marine macro- and microalgae as potential agents for the prevention of asthma: hyperresponsiveness and inflammatory subjects by Senevirathne M1, Kim SK.(PubMed)
(10) Iota-Carrageenan is a potent inhibitor of rhinovirus infection by Grassauer A1, Weinmuellner R, Meier C, Pretsch A, Prieschl-Grassauer E, Unger H.(PubMed)
(11) Active components of ginger potentiate β-agonist-induced relaxation of airway smooth muscle by modulating cytoskeletal regulatory proteins by Townsend EA1, Zhang Y, Xu C, Wakita R, Emala CW.(PubMed)
(12) Quercetin acutely relaxes airway smooth muscle and potentiates β-agonist-induced relaxation via dual phosphodiesterase inhibition of PLCβ and PDE4 by Townsend EA1, Emala CW Sr.(PubMed)
(13) Effects of ginger and its constituents on airway smooth muscle relaxation and calcium regulation by Townsend EA1, Siviski ME, Zhang Y, Xu C, Hoonjan B, Emala CW.(PubMed)
(14) Sulforaphane-rich broccoli sprout extract attenuates nasal allergic response to diesel exhaust particles by Heber D1, Li Z, Garcia-Lloret M, Wong AM, Lee TY, Thames G, Krak M, Zhang Y, Nel A.(PubMed)
(15) Sulforaphane inhibits the Th2 immune response in ovalbumin-induced asthma by Park JH1, Kim JW, Lee CM, Kim YD, Chung SW, Jung ID, Noh KT, Park JW, Heo DR, Shin YK, Seo JK, Park YM.(PubMed)
(16) Amelioration of asthmatic inflammation by an aqueous extract of Spinacia oleracea Linn by Heo JC1, Park CH, Lee HJ, Kim SO, Kim TH, Lee SH.(PubMed)
(17) Apple phytochemicals and their health benefits by Boyer J1, Liu RH.(PubMed)
(17a) Childhood asthma and fruit consumption by Okoko BJ1, Burney PG, Newson RB, Potts JF, Shaheen SO.(PubMed)
(18) A comprehensive review of apples and apple components and their relationship to human health by Hyson DA.(PubMed)
(19) Dietary antioxidants and asthma in adults: population-based case-control study by Shaheen SO1, Sterne JA, Thompson RL, Songhurst CE, Margetts BM, Burney PG.(PubMed)
(20) Dietary intake of flavonoids and asthma in adults by Garcia V1, Arts IC, Sterne JA, Thompson RL, Shaheen SO.(PubMed)
(21) Asthma: one hundred years of treatment and onward by Chu EK1, Drazen JM.(PubMed)
(22) Immunomodulating and Anti-Allergic Effects of Negroamaro and Koshu Vitis vinifera Fermented Grape Marc (FGM) by Marzulli G, Magrone T, Vonghia L, Kaneko M, Takimoto H, Kumazawa Y, Jirillo E(PubMed)
(23) Suppression of type-I allergic responses by oral administration of grape marc fermented with Lactobacillus plantarum by Tominaga T1, Kawaguchi K, Kanesaka M, Kawauchi H, Jirillo E, Kumazawa Y.(PubMed)
(24) Gallic acid inhibits histamine release and pro-inflammatory cytokine production in mast cells by Kim SH1, Jun CD, Suk K, Choi BJ, Lim H, Park S, Lee SH, Shin HY, Kim DK, Shin TY.(PubMed)
(25) Antiasthmatic effects of Galphimia glauca, gallic acid, and related compounds prevent allergen- and platelet-activating factor-induced bronchial obstruction as well as bronchial hyperreactivity in guinea pigs by Dorsch W1, Bittinger M, Kaas A, Müller A, Kreher B, Wagner H.(PubMed)
(26) Sesame oil attenuates ovalbumin-induced pulmonary edema and bronchial neutrophilic inflammation in mice by Hsu DZ1, Liu CT, Chu PY, Li YH, Periasamy S, Liu MY.(PubMed)
(27) Mechanisms by which botanical lipids affect inflammatory disorders by Chilton FH1, Rudel LL, Parks JS, Arm JP, Seeds MC.(PubMed)
(28) Respiratory and allergic diseases: from upper respiratory tract infections to asthma by Jaber R.(PubMed)
(29) Aqueous extract of the Helianthus annuus seed alleviates asthmatic symptoms in vivo by Heo JC1, Woo SU, Kweon MA, Park JY, Lee HK, Son M, Rho JR, Lee SH.(PubMed)
(30) Green tea (Camelia sinensis) mediated suppression of IgE production by peripheral blood mononuclear cells of allergic asthmatic humans by Wu SY1, Silverberg JI, Joks R, Durkin HG, Smith-Norowitz TA.(PubMed)
(31) Green tea (Camelia sinensis) suppresses B cell production of IgE without inducing apoptosis by Hassanain E1, Silverberg JI, Norowitz KB, Chice S, Bluth MH, Brody N, Joks R, Durkin HG, Smith-Norowitz TA.(PubMed)
(32) An aqueous extract of green tea Camellia sinensis increases expression of Th1 cell-specific anti-asthmatic markers by Heo JC1, Rho JR, Kim TH, Kim SY, Lee SH.(PubMed)
(33) Diet and obstructive lung diseases by Romieu I1, Trenga C.(PubMed)
(34) Respiratory and allergic diseases: from upper respiratory tract infections to asthma by Jaber R.(PubMed)
(35) Association between kimchi intake and asthma in Korean adults: the fourth and fifth Korea National Health and Nutrition Examination Survey (2007-2011) by Kim H1, Oh SY, Kang MH, Kim KN, Kim Y, Chang N.(PubMed)
(36) Diet and asthma in Dutch school children (ISAAC-2) by Tabak C1, Wijga AH, de Meer G, Janssen NA, Brunekreef B, Smit HA.(PubMed)
(37) Dietary factors in the pathogenesis of asthma and chronic obstructive pulmonary disease by Denny SI1, Thompson RL, Margetts BM.(PubMed)
(38) Coffee drinking and prevalence of bronchial asthma by Pagano R1, Negri E, Decarli A, La Vecchia C.(PubMed)
(39) Caffeine intake and asthma symptoms by Schwartz J1, Weiss ST.(PubMed)
(40) Caffeine for asthma by Welsh EJ1, Bara A, Barley E, Cates CJ.(PubMed)

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Asthma in Herbs’ points of view

Kyle J. Norton

Respiratory Disease is defined as medical conditions which affect the breathing organ and tissues including Inflammatory lung disease, Obstructive lung diseases, Restrictive lung diseases, Respiratory tract infections, trachea, bronchi, bronchioles, alveoli, the nerves and muscles breathing , etc.
Asthma is a chronic inflammatory disease affecting the air way of the lung with recurring symptoms, such as wheezing, chest tightness, shortness of breath, and coughing. The disease affects people of all ages, and mostly starts during childhood. According to American academy, allergy, asthma and immunology, about 1 in 10 children (10%) had asthma and 1 in 12 adults (8%) had asthma in 2009. (about 25 million, or 8% of the U.S. population)(1).
Epidemiological studies, linking herbs in reduced risk and treatment have been inconclusive(a)(b)(c)(d), but certain herbs have been found to be effectively in some studies.
1. Angelica sinensis (Oliv.)
Dang Qui (Angelica sinensis) is a herb of Genus Angelica from the family Apiaceae, indigenous to China. The herb has been used as a Queen herb in traditional Chinese medicine antispasmodic and vasodilatory agent, and to balance the hormones in women for a normal menstrual cycle and menstruation and strengthen heart, spleen, kidneys, and liver for both men and women, etc. In other words, it is used to treat gynecological ailments, fatigue, mild anemia and high blood pressure. It has analgesic, anti-inflammatory, etc. ethanolic extract (AD of Angelica in the study at Korea Institute of Oriental Medicine, showed to suppress airway allergic inflammation, by significantly lower airway eosinophilia, cytokine levels, including interleukin (IL)-4, IL-5, and tumor necrosis factor (TNF)-alpha levels, mucus production and immunoglobulin (Ig)E in mice(1). Danggui Buxue Tang, a composition of Angelica sinensis (AS) and Astragalus membranaceus (AM), in OVA-sensitized mice, its DBT2 or DBT3 showed no improved effects relative to DBT1 in treating asthmatic symptoms but DBT1 showed to suppress airway hyperresponsiveness and OVA-immunoglobulin E (IgE) in serum(2). According to Thammasat University, ethanol found in of Angelica sinensis exert its anti-inflammatory activity through antioxidant effects(3).

2. Ginkgo biloba
Ginkgo biloba is oldest living tree species, genus Ginkgo, belonging to the family Ginkgoaceae, native to China, from temperate zone to subtropical zone and some parts of north America. It Has been used in traditional herbal medicine in treating impotence, memory loss, respiratory diseases, circulatory disorders and deafness as well as preventing drunkenness, and bedwetting.
Ginkgolide B (GKB), a major chemical compound of ginkgo biloba, in BALB/c mice exerted its anti asthaasthmatic activity through inhibited the increase of T-helper 2 cytokines, such as interleukin (IL)-5 and IL-13 in bronchoalveolar lavage fluid (BALF) and decreased eosinophil count via inhibition of the ERK/MAPK signaling pathway(4). The composition of Ginkgo biloba leaf extract (EGb761), astaxanthin (ASX) and vitamin C, also showed to exhibit the inhibition of asthma-associated inflammation in asthmatic guinea-pigs(5) and Ginkgo biloba extracts showed to inhibit asthmatic disorder through suppression tof NF-kappaB gene expression actively in HL-60 cells(6). Accordiong to Dokuz Eylul University Hospital, biloba alleviates all established chronic histological changes of lung except smooth muscle thickness in a mouse model of asthma(7).

3. Licorice
Licorice (Glycyrrhiza Glabra) also known as sweetwood, is the genus Glycyrrhiza, belonging to the family Fabaceae, native to the Mediterranean and certain areas of Asia. The herb has been used in traditional medicine to treat skin diseases, coughs, constipation, bronchitis, inflammation, arthritis, etc. Licochalcone A (Lico A) isolated from the root of Xinjiang liquorice, exerted its anti-inflammatory activity on a non-infectious mouse model of asthma, through inhibition of the increase in T-helper type 2 cytokines and reduced serum levels of OVA-specific IgE and IgG(8). ASHMI, the composition of aqueous extracts of Lingzhi (Ganoderma lucidum), Kushen (Sophora flavescens) and Gancao (Glycyrrhiza uralensis), showed to allergic asthma, through inhibition of production of interleukin (IL)-4 and IL-5 by murine memory Th2 cells and eotaxin-1 production by HLF-1 cells(9).
Other study in a murine model also suggested that ASHMI not only significantly reduce eosinophilic pulmonary inflammation, serum IgE levels, IL-4 and IL-13 levels, but also increase IFN-γ production in lung cell cultures in response to antigen stimulation(10).

4. Chamomile
Chamomile is also known as camomile, common name of many species daisy-like plants in the family Asteraceae. The herb has been used in traditional medicine as antispasmodic and anti-inflammatory constituents and to treat menstrual cramps and sleep disorders, reduce cramping and spastic pain in the bowels, relieve excessive gas and bloating in the intestine, etc. Water composition extract of a mixture of eight herbs (chamomile, saffron, anise, fennel, caraway, licorice, cardomom and black seed), showed to alleviate the symptoms of asthma, through inhibition of histamine released from chemically- and immunologically-induced cells(11).

5. Garlic
Garlic (Allium sativum) is a species in the onion genus, belonging to family Amaryllidaceae, native to central Asia. It has been used popularly in traditional and Chinese medicine in treating common cold and flu to the Plague, blood pressure cholesterol levels, natural antibiotic, etc.
Diallyl disulfide (DADS), a major organosulfur compound found in garlic, in an ovalbumin-induced model of allergic asthma and RAW264.7 cells, showed to inhibit the proinflammatory proteins, through up regulation of Nrf-2/HO-1 and down regulation of NF-κB pathways(12). According to the study by Tarbiat Modares University, purified aged garlic extract exhibited the protective effect of asthma through a significant decrease in the hallmark criteria of allergic airway inflammation levels(13).

6. Grape seed extract
Grapefruit seed extract (GSE) is a liquid extracted from the seeds, pulp, and white membranes of grapefruit. The herb has been used in traditional medicine as an anti bacterial, viral, fungal, parasites and to enhance immune system, protect against colds and flu and malignant disease. Grape seed extract (GSPE) may alleviate the symptoms od asthma through its antioxidant activities. According to the study of University of Ulsan College of Medicine, GSPE effectively suppressed inflammation in both acute and chronic mouse models of asthma, through reduced airway hyperresponsiveness (AHR), decreased inflammatory cells in the BAL fluid, reduced lung inflammation and and decreased IL-4, IL-5, IL-13, and eotaxin-1 expression(14) by downregulating the iNOS expression(15). Other study suggested that GSE significantly ameliorated of the pathological changes of ovalbumin-induced asthma, through inhibition of altered the lung parenchyma pathology and inflammation in ovalbumin-induced murine asthma model(16).

7. Green Tea
Green tea contains more amount of antioxidants than any drinks or food with the same volume, and is the leaves of Camellia sinensis, undergone minimal oxidation during processing, originated from China. Green tea has been a precious drink in traditional Chinese culture and used exceptional in socialization for more than 4000 thousand years. Because of their health benefits, they have been cultivated for commercial purposes all over the world.
According to teh study at State University of New York Downstate Medical Center, green tea extract (GTE), and its major catechin, consisted an immunoregulatory effects through suppression of IgE production by peripheral blood mononuclear cells of allergic asthmatic patinets(17) and B cell production of IgE without inducing apoptosis(18). Other study suggested a anti asthmatic effect of aqueous extract of Camellia sinensis through increasing the expression level of tumor necrosis factor-beta and interferon-gamma and decreasing the expression of anti-asthmatic cytokines in the lung(19).

8. Ephedra sinica
Ephedra prepared from Ephedra sinica has been used in traditional Chinese medicine for 5,000 years to treat asthma, hypotension and fatigue, etc. In testing the effect of Ma huang water decoction, EWD and cough tablets containing ephedra and liquorice, MXCT, with theophylline (one of the most popular antiasthmatic drugs and a typical substrate of cytochrome P450 (CYP) 1A2, a enzyme in metabolism of xenobiotics), in rat, found the effectiveness of EWD or MXCT pretreatment in induced CYP1A2 activity, thus speeding up the metabolism of theophylline(20). Modified Shegan Mahuang Decoction (SGMH), in the study of a total of 154 children with cough and variant asthma (C&VA), exhibited the regulation of the serum levels of TNF-alpha (in the regulation of immune cells with function involved in induced fever, apoptotic cell death, cachexia, inflammation and to inhibit tumorigenesis and viral replication and respond to sepsis via IL1 & IL6 producing cells), IL-10( an anti-inflammatory cytokine) and IL-13(associated primarily with the induction of airway disease, and anti-inflammatory properties)(21), Other compositions of Herba Ephedrae decoction showed a strong effect in antianaphylaxis asthma(22).

9. Stinging nettle (Urtica dioica)
Sting Nettle is a flower plant in the genus Urtica, belonging tothe family Urticaceae, native to Europe, Africa, Asia, and North America.The herb has been used in traditional medicine as diuretic and laxative agent and to treat diarrhea and urinary disorders, to relieve pain, treat arthritis, asthma, bronchitis, sinusitis, etc. According to the Penn State University College of Medicine, extracts from the stinging nettle may provide therapeutic value for some inflammatory medical conditions, due to its released chemicals act to cause itching, dermatitis, and urticaria within moments of contact(23).

10. Boswellia
B. serrata gum resin extract (BSE) may be potential for the treatment of a variety of inflammatory diseases including inflammatory bowel disease, rheumatoid arthritis, osteoarthritis and asthma, according to Central Laboratory of German Pharmacists, Eschborn,(24) and Boswellic acids in some autoimmune diseases including rheumatoid arthritis, Crohn’s disease, ulcerative colitis and bronchial asthma, according to University of Tuebingen(25). The compositions of Boswellia serrata, licorice root (Glycyrrhiza glabra) and Tumeric root (Curcuma longa), in a total of 63 patients with bronchial asthma study, significantly decreased in the plasma levels of Plasma leukotriene C(4) (LTC(4))(,) nitric oxide (NO) and malondialdehyde (MDA) in target therapy group when compared with placebo group(26).

11. kava kava (Piper)
Kava Kava is a tall shrub, genus Piper, belonging to family Piperaceae, native to western Pacific. The herb has been used in traditional medicine as a drink for sedative and anesthetic effects and to treat anxiety, insomnia, etc.
kava kava (Piper) one most commonly used as complementary and alternative medicine (CAM) for treatment of asthma, allergy, and immunologic conditions, may display some adverse effects in the form of a hypersensitivity reaction(27). According to University of Aberdeen, kavain and flavokavains A and B treatment in asthmatic subjects enhanced anti-inflammatory mechanisms, through inhibition of both inhibitor of kappaB (IkappaB) degradation and subsequent translocation of p50 and p65 NF-kappaB subunits from the cytoplasm to the nucleus(28).

12. peppermint oil and leaf (Mentha)
Peppermint is a hybrid mint with small purple or white flowers and downy leaves, in the genus Mentha, belonging to the family Lamiaceae, native to to Europe. The herb has been used in folk medicine as analgesic, antiseptic, antispasmodic, decongestant, agent and to relieve gas, nausea, and stomach pain due to an irritable bowel, intestinal cramps, or indigestion, infecttion, etc.
Mentha, a majopr chemical constituent found in peppermint, its haplocalyx ethanol extract (MH), showed to inhibit inflammation of the airway in an asthmatic model, through inhibited increases in immunoglobulin (Ig) E and T-helper 2 (Th2)-type cytokines such as IL-4 and IL-5 in bronchoalveolar lavage fluid (BALF) and lung tissue(29).

13. Ginseng (Panax)
Ginseng is a slow-growing perennial plants with fleshy roots, the genus Panax, belonging to the family Araliaceae. Depending to the climate where it grows, ginseng can be classified mainly into Panax ginseng Asian ginseng (root), Red ginseng, wild ginseng, American ginseng (root).
According to Gachon University, Korean red ginseng (KRG) was found effectively in treating nasal allergic inflammatory reaction in an allergic murine model by reducing Th2 cytokines(30). RG-II, isolated from Panax ginseng, inhibited asthmatic reaction of an ovalbumin-induced murine model, through regulated the T(H)1/T(H)2 immune response(31). Other researchers suggested that Panax ginseng ameliorates airway inflammation through inhibited the numbers of goblet cells and further small G proteins and increased MAP kinases in bronchoalveolar lavage cells and lung tissues, in ovalbumin-induced allergic asthma in mice(32)

14. The compositions
14.1. Sho-seiryu-to (Xiao-Qing-Long-Tang)
Sho-seiryu-to (Xiao-Qing-Long-Tang) is a herbal composition included Chi Fu Ling, Gui Zhi, Bai Shao, Gan Jiang, Gan Cao, Zhi Ban Xia and Wu Wei Zi. According to the China Medical University, Xiao-Qing-Long-Tang (XQLT), inhibited the allergic inflammation including AHR, IgE elevation and eosinophil infiltration in Der p stimulated mice through regulating neurotrophin and reducing TARC(33) and also exhibited anti-airway inflammatory, anti-airway remodeling, and specific immunoregulatory effects in a chronic asthmatic mice model, through downregulated IL-10, IL-13, RANTES, Eotaxin, and MCP-1 mRNA expression in the lung(34). In the comparison of oral administration of 3 mg/day Shoseiryuto, 30 mg/day LFK, 3 mg/day of Shoseiryuto co-administered with 30 mg/day of LFK, and saline showed a significant reduction in the accumulation of eosinophils at 3 mg/day Shoseiryuto co-administered with 30 mg/day of LFK(35).

14.2. Ma-Xing-Gan-Shi-Tang (MXGST)
Ma-Xing-Gan-Shi-Tang (MXGST) is a Chinese herbal formula, included Ephedra, Apricot seed, R.Gypsum and Licorice frequently used in traditional Chinese medicine for asthmatic children in nationwide clinical database in Taiwan(36). According to the Institute of Chinese Medical Science, China Medical, College, Taichung, Taiwan, in actively sensitized guinea pig study, administration of MXGST (10 g/kg) extracts significantly inhibited the antigen induced immediate asthmatic responses(IAR), through stimulation of beta2-adrenoceptors on bronchial smooth muscle and its anti-inflammatory ability to inhibit the neutrophil into the airway(37).

Taking altogether, herbal medicine list above may be effective in prevention and treatment of asthma disorder, through reduction of air way inflammation via inhibition of histamine released from chemically- and immunologically-induced cells, etc. some researchers suggested that large sample size and muticenter studies are necessary with identification of the active principle in order to improve the validation of the clinical trial. As always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying.

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References
(1) Anti-asthmatic effects of Angelica dahurica against ovalbumin-induced airway inflammation via upregulation of heme oxygenase-1 by Lee MY1, Seo CS, Lee JA, Lee NH, Kim JH, Ha H, Zheng MS, Son JK, Shin HK.(PubMed)
(2) Danggui Buxue Tang attenuates eosinophil infiltration and airway hyperresponsiveness in asthmatic mice by Lin CC1, Liou CJ, Chiang CY, Huang WY, Huang WC.(PubMed)
(3) Antioxidant and nitric oxide inhibition activities of Thai medicinal plants by Makchuchit S1, Itharat A, Tewtrakul S.(PubMed)
(4) A novel anti-inflammatory role for ginkgolide B in asthma via inhibition of the ERK/MAPK signaling pathway by Chu X1, Ci X, He J, Wei M, Yang X, Cao Q, Li H, Guan S, Deng Y, Pang D, Deng X.(PubMed)
(5) Summative interaction between astaxanthin, Ginkgo biloba extract (EGb761) and vitamin C in suppression of respiratory inflammation: a comparison with ibuprofen by Haines DD1, Varga B, Bak I, Juhasz B, Mahmoud FF, Kalantari H, Gesztelyi R, Lekli I, Czompa A, Tosaki A(PubMed)
(6) [Studies on the effect of Ginkgo biloba extracts on NF-kappaB pathway].[Article in Chinese] by Li GH1, Lei XX, Yi YM, Xu BL, Wang HP, Du J.(PubMed)
(7) Effects of Ginkgo biloba on airway histology in a mouse model of chronic asthma by Babayigit A1, Olmez D, Karaman O, Ozogul C, Yilmaz O, Kivcak B, Erbil G, Uzuner N.(PubMed)
(8) Attenuation of allergic airway inflammation in a murine model of asthma by Licochalcone A by Chu X1, Jiang L, Wei M, Yang X, Guan M, Xie X, Wei J, Liu D, Wang D.(PubMed)
(9) Constituents of the anti-asthma herbal formula ASHMI(TM) synergistically inhibit IL-4 and IL-5 secretion by murine Th2 memory cells, and eotaxin by human lung fibroblasts in vitro by Jayaprakasam B1, Yang N, Wen MC, Wang R, Goldfarb J, Sampson H, Li XM.(PubMed)
(10) Glycyrrhiza uralensis flavonoids present in anti-asthma formula, ASHMI™, inhibit memory Th2 responses in vitro and in vivo by Yang N1, Patil S, Zhuge J, Wen MC, Bolleddula J, Doddaga S, Goldfarb J, Sampson HA, Li XM.(PubMed)
(11) The effect of a herbal water-extract on histamine release from mast cells and on allergic asthma by Haggag EG1, Abou-Moustafa MA, Boucher W, Theoharides TC.(PubMed)
(12) Diallyl-disulfide, an organosulfur compound of garlic, attenuates airway inflammation via activation of the Nrf-2/HO-1 pathway and NF-kappaB suppression by Shin IS1, Hong J, Jeon CM, Shin NR, Kwon OK, Kim HS, Kim JC, Oh SR, Ahn KS.(PubMed)
(13) Purified aged garlic extract modulates allergic airway inflammation in BALB/c mice by Zare A1, Farzaneh P, Pourpak Z, Zahedi F, Moin M, Shahabi S, Hassan ZM.(PubMed)
(14) Grape seed proanthocyanidin extract attenuates allergic inflammation in murine models of asthma by Lee T1, Kwon HS, Bang BR, Lee YS, Park MY, Moon KA, Kim TB, Lee KY, Moon HB, Cho YS.(PubMed)
(15) Grape seed proanthocyanidin extract attenuates airway inflammation and hyperresponsiveness in a murine model of asthma by downregulating inducible nitric oxide synthase by Zhou DY1, Du Q, Li RR, Huang M, Zhang Q, Wei GZ.(PubMed)
(16) Grape seed extract attenuates lung parenchyma pathology in ovalbumin-induced mouse asthma model: an ultrastructural study by Mahmoud YI.(PubMed)
(17) Green tea (Camelia sinensis) mediated suppression of IgE production by peripheral blood mononuclear cells of allergic asthmatic humans by Wu SY1, Silverberg JI, Joks R, Durkin HG, Smith-Norowitz TA.(PubMed)
(18) Green tea (Camelia sinensis) suppresses B cell production of IgE without inducing apoptosis by Hassanain E1, Silverberg JI, Norowitz KB, Chice S, Bluth MH, Brody N, Joks R, Durkin HG, Smith-Norowitz TA.(PubMed)
(19) An aqueous extract of green tea Camellia sinensis increases expression of Th1 cell-specific anti-asthmatic markers by Heo JC1, Rho JR, Kim TH, Kim SY, Lee SH.(PubMed)
(20) Effects of ephedra water decoction and cough tablets containing ephedra and liquorice on CYP1A2 and the pharmacokinetics of theophylline in rats by Tang J1, Zhou X, Ji H, Zhu D, Wu L.(PubMed)
(21) [Effect of modified shegan mahuang decoction on cytokines in children patients with cough and variant asthma].[Article in Chinese]by Chen ZX1, Hu GH.(PubMed)
(22)[Effects of among compositions of Herba Ephedrae decoction on genic xpression of 5-lipoxygenase activating protein, IL-4 and leukotriene C4 in asthmatic mice].[Article in Chinese]by Liu YG1, Luo JB.(PubMed)
(23) Stinging nettle dermatitis by Anderson BE1, Miller CJ, Adams DR(PubMed)
(24) Boswellia serrata: an overall assessment of in vitro, preclinical, pharmacokinetic and clinical data by Abdel-Tawab M1, Werz O, Schubert-Zsilavecz M.(PubMed)
(25) Boswellic acids in chronic inflammatory diseases by Ammon HP.(PubMed)
(26) Natural anti-inflammatory products and leukotriene inhibitors as complementary therapy for bronchial asthma by Houssen ME1, Ragab A, Mesbah A, El-Samanoudy AZ, Othman G, Moustafa AF, Badria FA.(PubMed)
(27) Complementary and alternative interventions in asthma, allergy, and immunology by Bielory L.(PubMed)
(28) Inhibition of TNFalpha-induced activation of nuclear factor kappaB by kava (Piper methysticum) derivatives by Folmer F1, Blasius R, Morceau F, Tabudravu J, Dicato M, Jaspars M, Diederich M.(PubMed)
(29) Protective effects of Mentha haplocalyx ethanol extract (MH) in a mouse model of allergic asthma by Lee MY1, Lee JA, Seo CS, Ha H, Lee NH, Shin HK.(PubMed)
(30) The effect of Korean red ginseng on allergic inflammation in a murine model of allergic rhinitis by Jung JH1, Kang IG, Kim DY, Hwang YJ, Kim ST.(PubMed)
(31) RG-II from Panax ginseng C.A. Meyer suppresses asthmatic reaction by Jung ID1, Kim HY, Park JW, Lee CM, Noh KT, Kang HK, Heo DR, Lee SJ, Son KH, Park HJ, Shin SJ, Park JH, Ryu SW, Park YM.(PubMed)
(32) Panax ginseng ameliorates airway inflammation in an ovalbumin-sensitized mouse allergic asthma model by Kim DY1, Yang WM.(PubMed)
(33) Xiao-Qing-Long-Tang shows preventive effect of asthma in an allergic asthma mouse model through neurotrophin regulation by Chang RS1, Wang SD, Wang YC, Lin LJ, Kao ST, Wang JY.(PubMed)
(34) Xiao-Qing-Long-Tang attenuates allergic airway inflammation and remodeling in repetitive Dermatogoides pteronyssinus challenged chronic asthmatic mice model by Wang SD1, Lin LJ, Chen CL, Lee SC, Lin CC, Wang JY, Kao ST.(PubMed)
(35) Enhancement of anti-allergic effects mediated by the Kampo medicine Shoseiryuto (Xiao-Qing-Long-Tang in Chinese) with lysed Enterococcus faecalis FK-23 in mice by Shimada T1, Kondoh M, Motonaga C, Kitamura Y, Cheng L, Shi H, Enomoto T, Tsuruta D, Ishii M, Kobayashi H.(PubMed)
(36) Identifying core herbal treatments for children with asthma: implication from a chinese herbal medicine database in Taiwan by Chen HY1, Lin YH, Thien PF, Chang SC, Chen YC, Lo SS, Yang SH, Chen JL.(PubMed)
(37) The effects of Ma-Xing-Gan-Shi-Tang on respiratory resistance and airway leukocyte infiltration in asthmatic guinea pigs by Kao ST1, Yeh TJ, Hsieh CC, Shiau HB, Yeh FT, Lin JG.
(PubMed)

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Skin aging in Vitamin B3 points of view

Skin aging is one of most visible process which occurs constantly in our skin organ. According to the Clinical Centre of Nis, certain plant extracts may have the ability to scavenge free radicals, to protect the skin matrix through the inhibition of enzymatic degradation, or to promote collagen synthesis in the skin, affect skin elasticity and tightness(a). Other suggested that free radicals induced domino effects in production of reactive oxygen species, can react with DNA, proteins, and fatty acids, causing oxidative damage and impairment of antioxidant system, leading injuries damage regulation pathways of skin, including wrinkles, roughness, appearance of fine lines, lack of elasticity, and de- or hyperpigmentation marks(b).
Niacin, is also known as vitamin B3, nicotinic acid, an organic compound with the formula
C6H5NO2, found abundantly in chicken, beef, fish, cereal, peanuts and legumes. It is best known for its effects in lowering cholesterol and triglycerides and removing toxic from our body and promoting production of steroid hormones.

Vitamin B3 may be effective to protect against skin-aging through its antioxidant activity(1)(2)(3) such as allowness, wrinkling, red blotchiness and hyperpigmented spots(3a)
In the comparison of the effect on aging skin among a cosmetic niacinamide/peptide/retinyl propionate product regimen vs. a prescription 0.02% tretinoin product regimen, researchers at the showed that the composition significantly improved wrinkle appearance after 8 weeks relative to tretinoin, with comparable benefits after 24 weeks with well tolerate adverse effects(4). In facial hyperpigmentation, composition of topical niacinamide and N-acetyl reduced the appearance of irregular pigmentation including hypermelaninization(5) and niacinamide alone enhanced skin lightening, and hyperpigmented lesions(6) through inhibiting melanosome transfer from melanocytes to keratinocytes(7). A daily facial lotion application containing vitamins B3 and E and provitamin B5 on the facial skin of Indian women, 30-60 years of age, for 10 weeks, showed a significantly reduced appearance of hyperpigmentation, improved skin tone evenness, appearance of lightening of skin, and positive effects on skin texture, as early as 6 weeks(8). In Global gene expression skin aging process, compounds niacinamide and hexamidine, may effect the skin hydration, barrier, matrix, pigmentation through theirs’ antioxidant capacity(9). According to Kinki University School of Medicine, application of composition containing 4% niacinamide in 30 healthy Japanese females who had wrinkles in the eye areas showed to reduced wrinkles in the eye areas through a marked and moderate improvement in 64% of the subjects with a significant difference as compared with the control site(10) and niacinamide aloneexhibited a significant reductions in fine lines and wrinkles, hyperpigmented spots, red blotchiness, and skin sallowness (yellowing)(11)(12).

Taken altogether, strong evidence suggested that vitamin B3 used alone or combination with other antioxidants may be beneficial in reduced the early onset skin aging and skin aging progression. Overdoses of vitamin B3 may induce symptoms of severe skin flushing combined with dizziness, rapid heartbeat, itching, nausea, vomiting, abdominal pain, etc. As always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying.

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References
(a) Skin ageing: natural weapons and strategies by Binic I1, Lazarevic V, Ljubenovic M, Mojsa J, Sokolovic D.(PubMed)
(b) Phytoconstituents as photoprotective novel cosmetic formulations by Saraf S1, Kaur CD.(PubMed)
(1) [Anti-aging creams. What really helps?].[Article in German] by Kerscher M1, Buntrock H.(PubMed)
(2) Practical application of cellular bioenergetics to the care of aged skin by Osborne R1, Carver RS, Mullins LA, Finlay DR(PubMed)
(3) Application of genomics to breakthroughs in the cosmetic treatment of skin ageing and discoloration by Osborne R1, Hakozaki T, Laughlin T, Finlay DR.(PubMed)
(3a) Evaluation of anti-wrinkle effects of a novel cosmetic containing niacinamide by Kawada A1, Konishi N, Oiso N, Kawara S, Date A.([PubMed)
(4) A randomized, controlled comparative study of the wrinkle reduction benefits of a cosmetic niacinamide/peptide/retinyl propionate product regimen vs. a prescription 0.02% tretinoin product regimen by Fu JJ1, Hillebrand GG, Raleigh P, Li J, Marmor MJ, Bertucci V, Grimes PE, Mandy SH, Perez MI, Weinkle SH, Kaczvinsky JR.(PubMed)
(5) Reduction in the appearance of facial hyperpigmentation after use of moisturizers with a combination of topical niacinamide and N-acetyl glucosamine: results of a randomized, double-blind, vehicle-controlled trial by Kimball AB1, Kaczvinsky JR, Li J, Robinson LR, Matts PJ, Berge CA, Miyamoto K, Bissett DL(PubMed)
(6) Effective inhibition of melanosome transfer to keratinocytes by lectins and niacinamide is reversible by Greatens A1, Hakozaki T, Koshoffer A, Epstein H, Schwemberger S, Babcock G, Bissett D, Takiwaki H, Arase S, Wickett RR, Boissy RE(PubMed)
(7) The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer by Hakozaki T1, Minwalla L, Zhuang J, Chhoa M, Matsubara A, Miyamoto K, Greatens A, Hillebrand GG, Bissett DL, Boissy RE(PubMed)
(8) The effects of a daily facial lotion containing vitamins B3 and E and provitamin B5 on the facial skin of Indian women: a randomized, double-blind trial by Jerajani HR1, Mizoguchi H, Li J, Whittenbarger DJ, Marmor MJ.(PubMed)
(9) Understanding metabolic pathways for skin anti-aging by Osborne R1, Mullins LA, Jarrold BB.(PubMed).
(10) Evaluation of anti-wrinkle effects of a novel cosmetic containing niacinamide by Kawada A1, Konishi N, Oiso N, Kawara S, Date A.(PubMed)
(11) Niacinamide: A B vitamin that improves aging facial skin appearance by Bissett DL1, Oblong JE, Berge CA(PubMed)
(12) Topical niacinamide reduces yellowing, wrinkling, red blotchiness, and hyperpigmented spots in aging facial skin by Bissett DL1, Miyamoto K, Sun P, Li J, Berge CA.(PubMed)

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Skin aging in Vitamin E points of view

Skin aging is one of most visible process which occurs constantly in our skin organ. According to the Clinical Centre of Nis, certain plant extracts may have the ability to scavenge free radicals, to protect the skin matrix through the inhibition of enzymatic degradation, or to promote collagen synthesis in the skin, affect skin elasticity and tightness(a). Other suggested that free radicals induced domino effects in production of reactive oxygen species, can react with DNA, proteins, and fatty acids, causing oxidative damage and impairment of antioxidant system, leading injuries damage regulation pathways of skin, including wrinkles, roughness, appearance of fine lines, lack of elasticity, and de- or hyperpigmentation marks(b).
Vitamin E, a fat soluble vitamin, consisting eight different variants (alpha-, beta-, gamma-, and delta-tocopherol and alpha-, beta-, gamma-, and delta-tocotrienol) with varying levels of biological activity(2), found abundantly in corn oil, soybean oil, margarine, wheat germ oil, sunflower,safflower oils, etc. plays an important role in neurological functions and inhibition of platelet aggregation, regulation of enzymatic activity, free radical scavenger, etc..

Epidemiological studies, linking vitamin E in reduced progression of aging have been inconclusive(1)(2)(3)(4).
The effects
According to the Universiti Kebangsaan Malaysia, in stress-induced premature senescence (SIPS) model of human diploid fibroblasts (HDFs), γ-tocotrienol (GTT), a vitamin E variant showed to delay cellular senescence of human diploid fibroblasts through the inhibition of intrinsic mitochondria-mediated pathway which involved the regulation of pro- and anti-apoptotic genes and proteins(5) and prevented cellular aging in human diploid fibroblasts(6), probably through modulating gene expression(7) and protected against oxidative stress-induced cellular ageing by modulating the telomere length possibly via telomerase(8). The molecular mechanism of tocotrienol-rich fraction (TRF) study insisted that the variants protected against H(2)O(2)-induced oxidative stress in human skin fibroblast culture by modulating the expression of COL I and COL III genes with concomitant increase in the rate of total collagen synthesis(9). According to the National University of Malaysia, f alpha-tocopherol (ATF), another variant of vitamin E protected against H(2)O(2)-induced DNA damage and telomere shortening of normal human skin fibroblast cells derived from young and old individual donors(10) and topical administration of alpha-tocopherol (ATF), in medium doses, may provided some degree of photoprotection against UVA(11). Some researchers suggested the potent of vitamins in reduced aging progression is a result of the balance between various skin antioxidants of vitamin E and C, through new delivery systems, in delivering vitamins C and E into the skin simultaneously(12). Other antioxidant in improved skin health, include vitamin E, certain flavonoids, and the carotenoids, β-carotene, lycopene and lutein, may also effective through protection against inflammation, oxidative stress, breakdown of the extracellular matrix(13). In Indian women with facial signs of aging study, the composition of niacinamide, panthenol, and tocopheryl acetate significantly reduced appearance of hyperpigmentation, improved skin tone evenness, appearance of lightening of skin, versus control in 6 weeks(14).

Taken altogether, composition of vitamin E and other antioxidants and its variants may be effective
in reduced early onset of skin aging and inhibited skin aging progression, but large sample size and multi centers studies to improved these validation are necessary. Over doses of vitamin E supplement can cause symptoms of blurred vision, weakness, dizziness, nausea, diarrhea, etc., please make sure you follow the guideline of the Institute of Medicine of the National Academies.

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References
(1) Evaluation of the photoprotective effect of oral vitamin E supplementation by Werninghaus K1, Meydani M, Bhawan J, Margolis R, Blumberg JB, Gilchrest BA.(PubMed)
(2) Protective effect against sunburn of combined systemic ascorbic acid (vitamin C) and d-alpha-tocopherol (vitamin E) by Eberlein-König B1, Placzek M, Przybilla B(PubMed)
(3) Effects of oral vitamin E and beta-carotene supplementation on ultraviolet radiation-induced oxidative stress in human skin by McArdle F1, Rhodes LE, Parslew RA, Close GL, Jack CI, Friedmann PS, Jackson MJ(PubMed)
(4) Effect of UV exposure and beta-carotene supplementation on delayed-type hypersensitivity response in healthy older men by Herraiz LA1, Hsieh WC, Parker RS, Swanson JE, Bendich A, Roe DA.(PubMed)
(5) Inhibition of mitochondrial cytochrome c release and suppression of caspases by gamma-tocotrienol prevent apoptosis and delay aging in stress-induced premature senescence of skin fibroblasts by Makpol S1, Abdul Rahim N, Hui CK, Ngah WZ(PubMed)
(6) Gamma-tocotrienol modulation of senescence-associated gene expression prevents cellular aging in human diploid fibroblasts by Makpol S1, Zainuddin A, Chua KH, Yusof YA, Ngah WZ.(PubMed)
(7) Gamma-tocotrienol modulated gene expression in senescent human diploid fibroblasts as revealed by microarray analysis by Makpol S1, Zainuddin A, Chua KH, Mohd Yusof YA, Ngah WZ.(PubMed)
(8) Gamma-Tocotrienol prevents oxidative stress-induced telomere shortening in human fibroblasts derived from different aged individuals by Makpol S1, Abidin AZ, Sairin K, Mazlan M, Top GM, Ngah WZ.(PubMed)
(9) Modulation of collagen synthesis and its gene expression in human skin fibroblasts by tocotrienol-rich fraction by Makpol S1, Azura Jam F, Anum Mohd Yusof Y, Zurinah Wan Ngah W.(PubMed)
(10) Alpha-tocopherol modulates hydrogen peroxide-induced DNA damage and telomere shortening of human skin fibroblasts derived from differently aged individuals by Makpol S1, Zainuddin A, Rahim NA, Yusof YA, Ngah WZ.(PubMed)
(11) A pilot study of the photoprotective effect of almond phytochemicals in a 3D human skin equivalent by Evans-Johnson JA1, Garlick JA, Johnson EJ, Wang XD, Oliver Chen CY.(PubMed)
(11) Main approaches for delivering antioxidant vitamins through the skin to prevent skin ageing by Gašperlin M1, Gosenca M(PubMed)
(12) The role of phytonutrients in skin health by Evans JA1, Johnson EJ.(PubMed)
(14) The effects of a daily facial lotion containing vitamins B3 and E and provitamin B5 on the facial skin of Indian women: a randomized, double-blind trial by Jerajani HR1, Mizoguchi H, Li J, Whittenbarger DJ, Marmor MJ.(PubMed)

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