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 summarized 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)(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)