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The role of zinc in acne and prevention of resistance: Have we missed the "base" effect?
Abstract
where the use of oral zinc sul-fate was not associated with significant improvement inrosacea severity over a 90-day trial is contrary to existingliterature, though this can be explained by the differencein population race/ethnicity and dietary conditions. Wefeel that the issue of the effects of zinc in acne vulgarisand rosacea should focus on the preparation of zinc used.The available preparations include zinc acetate, zinc octo-ate, zinc citrate, zinc picolinate, zinc ascorbate, zinc glu-conate, and methionine-bound zinc.
... We agree with Sardana et al. 1 regarding the importance of the ongoing search for safe, inexpensive, and effective treatment for rosacea. The identification of new treatment options will hinge in large part on improving our understanding of the pathogenesis of rosacea and therefore in differentiating between the pathogenesis of rosacea and that of other inflammatory conditions such as acne vulgaris. ...
... 5 Moreover, the role of inflammation varies in the different subtypes of rosacea, and accordingly the efficacy of zinc in the management of rosacea may be expected to be variableat best. Unfortunately, the commentary by Sardana et al. 1 addresses acne vulgaris and rosacea together, which makes their findings difficult to interpret. ...
... The principal point by Sardana et al. 1 is that the bioavailability of zinc varies substantially in different formulations and that several oral preparations of zincparticularly methionine-bound zincare associated with better bioavailability than zinc sulfate. The quantity of zinc absorbed is affected not only by the type of zinc preparation used but also by factors such as the quantity of zinc ingested, the time over which the zinc is ingested, and the age of the patient. ...
... It is well known that zinc has adequate effect on stronger emergence, faster stand establishment, healthier root growth, greater potential vigor and increased yield potential. Data regarding the effect of zinc on the yield attributes of late sown wheat is given in Table 1 and other growth attributes presented in Table 2. Sardana et al. (2014) [8] studied the effect of N (120-150 kg /ha); P (60 kg P 2 O 5 /ha); K 2 O (30 and 60 kg/ha): ZnSO 4 (25 and 50kg/ha) on durum wheat cultivars PBW 233. Fertilizer application significantly increased the grain yield. ...
... It is well known that zinc has adequate effect on stronger emergence, faster stand establishment, healthier root growth, greater potential vigor and increased yield potential. Data regarding the effect of zinc on the yield attributes of late sown wheat is given in Table 1 and other growth attributes presented in Table 2. Sardana et al. (2014) [8] studied the effect of N (120-150 kg /ha); P (60 kg P 2 O 5 /ha); K 2 O (30 and 60 kg/ha): ZnSO 4 (25 and 50kg/ha) on durum wheat cultivars PBW 233. Fertilizer application significantly increased the grain yield. ...
... It was later determined that zinc levels in those with acne were significantly lower than controls . Although the exact mechanism by which zinc exerts its effects to improve acne vulgaris is not fully understood, current knowledge suggests multiple mechanisms (Azzouni, Godoy, Li, & Mohler, 2012;Chow, 2009;Gupta, Mahajan, Mehta, & Chauhan, 2014;Kitamura et al., 2006;Ozuguz et al., 2014;Sardana, Chugh, & Garg, 2014;Sugimoto, L opez-Solache, Labrie, & Luu-The, 1995): ...
... 7. Inhibition of integrin and toll-like receptor expression by keratinocytes, thus acting as an anti-inflammatory agent (Kitamura et al., 2006) (Note: P. acnes induces cytokine production through a tolllike receptor-dependent pathway) (Sardana et al., 2014). ...
Acne vulgaris is a chronic disease of the pilosebaceous units presenting as inflammatory or noninflammatory lesions in individuals of all ages. The current standard of treatment includes topical formulations in the forms of washes, gels, lotions, and creams such as antibiotics, antibacterial agents, retinoids, and comedolytics. Additionally, systemic treatments are available for more severe or resistant forms of acne. Nevertheless, these treatments have shown to induce a wide array of adverse effects, including dryness, peeling, erythema, and even fetal defects and embolic events. Zinc is a promising alternative to other acne treatments owing to its low cost, efficacy, and lack of systemic side effects. In this literature review, we evaluate the effectiveness and side-effect profiles of various formulations of zinc used to treat acne.
... Moreover, zinc inhibits interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα) production and modulates expression of integrins, mainly intracellular adhesion molecule-(ICAM-) 1 and leucocyte function associated antigen (7) . ...
... Moreover, zinc ions were found to reduce antibiotic resistance [17] and increase their topical absorption rate (as for erythromycin) [6]. In addition, the effects of zinc compounds in acne might exceed those for some antibiotic therapies [18]. Taking into account the growing antibiotic resistance problem [19,20], there is a need to identify new non-antibiotic solutions for acne treatment. ...
Zinc compounds have a number of beneficial properties for the skin, including antimicrobial, sebostatic and demulcent activities. The aim of the study was to develop new anti-acne preparations containing zinc–amino acid complexes as active ingredients. Firstly, the cytotoxicity of the zinc complexes was evaluated against human skin fibroblasts (1BR.3.N cell line) and human epidermal keratinocyte cell lines, and their antimicrobial activity was determined against Cutibacterium acnes. Then, zinc complexes of glycine and histidine were selected to create original gel formulations. The stability (by measuring pH, density and viscosity), microbiological purity (referring to PN-EN ISO standards) and efficacy of the preservative system (according to Ph. Eur. 10 methodology) for the preparations were evaluated. Skin tolerance was determined in a group of 25 healthy volunteers by the patch test. The preparations containing zinc(II) complexes with glycine and histidine as active substances can be topically used in the treatment of acne skin due to their high antibacterial activity against C. acnes and low cytotoxicity for the skin cells. Dermatological recipes have been appropriately composed; no irritation or allergy was observed, and the preparations showed high microbiological purity and physicochemical stability.
... In a recent review, zinc was reported to be effective in the treatment of acne vulgaris [26]. Among various functions, zinc plays a role in many processes that may affect the development of SD [6,[38][39][40][41][42][43]. Zinc affects the regulation of protein, lipid, and nucleic acid metabolism, acting as a cofactor in metalloenzymes and transcription factors. ...
Background/aim:
Malassezia colonization, sebaceous gland activity, hormones, immune system defects, environmental factors, and the interactions between these factors are thought to contribute to the pathogenesis of seborrheic dermatitis (SD). Zinc, an essential element, is involved in many biological processes including the ones that contribute to the development of SD. The aim of this study is to evaluate serum zinc levels in patients with SD.
Materials and methods:
Forty-three patients with SD and 41 healthy controls were enrolled in the study. Disease activity was assessed by the Seborrheic Dermatitis Area and Severity Index by a single dermatologist. Serum zinc levels of all subjects were evaluated.
Results:
Statistically significantly lower serum zinc levels were noted in SD patients than in the control group (79.16 ± 12.17 vs. 84.88 ± 13.59, respectively; P = 0.045).
Conclusion:
The results of the study demonstrated that patients who had SD had lower levels of serum zinc levels than healthy subjects.
... [28,44,45] To minimize the resistance problem certain measures are advocated, like avoiding antibiotics for milder forms of acne and using antibiotics in combination with topical retinoids or BPO if antibiotics must be administrated for longer than 2 months. [27,28,[45][46][47] Probably adding other agents such as zinc and azealic acid may help to obviate the development of resistance. [27,47,48] However, the misuse of antibiotics in acne, if they exceed the MIC levels "in vitro," will lead to an epidemiological problem and predispose to transfer of resistance to other organisms and patients. ...
Background:
Antibiotic resistance is a worldwide problem in acne patients due to regional prescription practices, patient compliance, and genomic variability in Propionibacterium acnes, though the effect of treatment on the resistance has not been comprehensively analyzed.
Aims:
Our primary objective was to assess the level of antibiotic resistance in the Indian patients and to assess whether there was a difference in the resistance across common treatment groups.
Subjects and methods:
A cross-sectional, institutional based study was undertaken and three groups of patients were analyzed, treatment naïve, those on antibiotics and patients on benzoyl peroxide (BPO) and/isotretinoin. The follicular content was sampled and the culture was verified with 16S rRNA polymerase chain reaction, genomic sequencing, and pulsed-field gel electrophoresis. Minimum inhibitory concentration (MIC) assessment was done for erythromycin (ERY), azithromycin (AZI), clindamycin (CL), tetracycline (TET), doxycycline (DOX), minocycline (MINO), and levofloxacin (LEVO). The four groups of patients were compared for any difference in the resistant strains.
Results:
Of the 52 P. acnes strains isolated (80 patients), high resistance was observed to AZI (100%), ERY (98%), CL (90.4%), DOX (44.2%), and TETs (30.8%). Low resistance was observed to MINO (1.9%) and LEVO (9.6%). Statistical difference was seen in the resistance between CL and TETs; DOX/LEVO and DOX/MINO (P < 0.001). High MIC90 (≥256 μg/ml) was seen with CL, macrolides, and TETs; moreover, low MIC90 was observed to DOX (16 μg/ml), MINO (8 μg/ml), and LEVO (4 μg/ml). Though the treatment group with isotretinoin/BPO had the least number of resistant strains there was no statistical difference in the antibiotic resistance among the various groups of patients.
Conclusions:
High resistance was seen among the P. acnes strains to macrolides-lincosamides (AZI and CL) while MINO and LEVO resistance was low.
The complicated and multifactorial nature of acne pathophysiology provides a multitude of opportunities for vitamins and minerals to disrupt the inflammatory cascade. In their traditional roles as dietary necessities, vitamins and minerals participate in keratinocyte proliferation and maturation, modulation of lipid production in human sebocytes, and inhibition of pro-inflammatory cytokines, matrix metalloproteinases, and antimicrobial peptides, as well as act as antioxidants. Not surprisingly, then, there is considerable in vitro and preclinical data predicting their efficacy in acne. Although conclusive clinical evidence is currently lacking for many of them, more vigorous trials are being conducted with increasingly convincing in vivo data. At this time, data for vitamin A analogs, zinc, and niacinamide is most compelling. It may well be that combination therapy will be more efficacious than monotherapy. Fortunately, due to their large safety margin, we can afford to be generous with our recommendations while awaiting more definitive results.
Antibiotic resistance in cutaneous Propionobacterium is a global problem. As a general rule, resistance levels are high to macrolides, trimethoprim/sulfamethoxazole and clindamycin, while tetracyclines and levofloxacin have low resistance potential. Newer preparations like doxycycline MR and doxycycline 20 mg are subantimicrobial and may not lead to resistance. Sampling techniques are crucial to determine resistance. Genomic evaluation using 16S ribosomal RNA gene sequencing can be useful in diagnosing mutations and mapping phylotypes of Propionobacterium acnes. Resistance may lead to slow response and relapses. Apart from benzoyl peroxide, azelaic acid, topical dapsone, oral zinc and retinoids, novel molecules with little resistance potential include octadecenedioic acid, phytosphingosine, lauric acid, retapamulin, resveratrol, T-3912 and NB-003. The use of oral retinoids and non-antibiotics like zinc can prevent resistance and help reduce the dependence on antibiotics.
Many patients seek alternative and complementary therapies, particularly when diseases are incurable or when conventional treatments have undesirable side effects that are real or perceived. This article reviews some selective evidence behind alternative therapies utilized in the treatment of three common diseases in pediatric dermatology: atopic dermatitis, acne vulgaris, and cutaneous warts. While some show promise, the treatments discussed vary greatly in the quality and quantity of supporting evidence and should be carefully considered when advising patients on their use.
The in vitro antimicrobial activity of ascorbic acid derivatives against Propionibacterium acnes was tested either alone or in combination with a variety of antimicrobial agents, and their fractional inhibitory concentration index was determined using checkerboard tests. The antimicrobial effectiveness of zinc ascorbate in the treatment of acne vulgaris, either alone or in combination with antibiotics such as clindamycin that are commonly used in Japan for the treatment of acne vulgaris, was therefore examined.
The antimicrobial susceptibility of 41 strains of clindamycin-sensitive and/or clindamycin-resistant P. acnes isolated from acne vulgaris patients was tested, in comparison with a type strain of P. acnes.
Zinc ascorbate showed antimicrobial activity against a type strain of P. acnes and its concentration (0.064%) was sufficiently lower than the normal dose (5%) of other ascorbic acid derivatives. Combinations of zinc ascorbate with clindamycin, erythromycin, and chloramphenicol showed an additive effect, and zinc ascorbate alone effectively inhibited the growth of all P. acnes including clindamycin-resistant strains.
The results provide novel evidence that the combination of zinc ascorbate and clindamycin is effective for acne vulgaris treatment.
The bioavailability of zinc-methionine (ZnMET) was compared to that of feed-grade ZnSO4.H2O using three different diets: purified (crystalline amino acid [AA]), semipurified (soy isolate), and complex (corn-soybean [C-SBM]) diet. With the Zn-deficient purified or semipurified diet, weight gain and tibia Zn responded linearly to both ZnSO4.H2O and ZnMET supplementation. Common-intercept, multiple linear regression indicated differences in Zn bioavailability between ZnMET and ZnSO4.H2O for both diets as indicated by bone Zn. With the ZnSO4.H2O standard set at 100%, bioavailability of Zn from ZnMET was 117% (P less than .05) in the AA diet and 177% (P less than .01) in the soy isolate diet. The ZnMET was also compared to ZnSO4.H2O in a C-SBM diet containing 117 mg of Zn/kg. When high levels of Zn were added to this diet (0, 250, 500, and 750 mg/kg of supplemental Zn), consistent tissue Zn responses did not occur beyond the first increment. Addition of lower levels of supplemental Zn (0, 5, 10, 20, 30, 40 and 50 mg/kg) to a Zn-unsupplemented C-SBM basal diet (45 mg/kg of Zn), however, resulted in a broken-line, two-slope response in tibia Zn for both ZnMET and ZnSO4.H2O. Inflection points occurred at 60 and 54 mg of Zn/kg of diet for ZnSO4.H2O and ZnMET, respectively. The ratio of slopes (ZnMET:ZnSO4.H2O) below the inflection points was 206% (P less than .01), indicating that Zn was considerably more bioavailable in ZnMET than in ZnSO4.H2O for chicks consuming C-SBM diets. When feed-grade ZnO was compared to feed-grade ZnSO4.H2O in chicks consuming C-SBM diets, bone Zn slopes below the respective inflection points indicated that Zn was 61% bioavailable in ZnO relative to ZnSO4.H2O.
Tetracyclines and macrolide antibiotics have been in use for acne treatment for more than 20 years. Since 1992 increasing resistance to these antibiotics, and especially to erythromycin, is reported with Propionibacterium acnes. Zinc salts have demonstrated their efficacy in inflammatory acne treatment as well as their bacteriostatic activity against Propionibacterium acnes. The objective of our work was firstly to determine whether the clinical anti-inflammatory efficacy of zinc salts was altered in the presence of erythromycin resistant strains in vivo, and secondly to study the in vitro and in vivo effect of zinc on the sensitivity of Propionibacterium acnes strains to erythromycin. Thirty patients with inflammatory acne were treated by zinc gluconate with a daily dose of 30 mg for two months and bacteriologic samples were taken at D0, D30 and D60. In vivo, this study displayed a reduction in the number of inflammatory lesions after a 2-month treatment whether or not Propionibacterium acnes carriage was present. Concurrently, in vitro addition of zinc salts in the culture media of Propionibacterium acnes reduced resistance of Propionibacterium acnes strains to erythromycin. Thus, association of zinc salts via a systemic route and topical erythromycin treatment seems an interesting option in the light of an increasing number of patients carrying erythromycin resistant Propionibacterium acnes strains.
A 2006 article published in the International Journal of Dermatology reported that oral zinc sulfate 100 mg three times daily was associated with improvement in the severity of facial rosacea (Sharquie et al. 2006; 45: 857-861). The current study was undertaken to further assess the role of zinc in the management of rosacea. This was a randomized, double-blind trial of 220 mg of zinc sulfate twice daily for 90 days in patients with moderately severe facial rosacea at baseline. Subjects were recruited in the Upper Midwest USA between August 2006 and April 2008, and followed until July 2008. Forty-four subjects completed the trial (22 in each arm). Rosacea improved in both groups. There were no differences in magnitude of improvement based on rosacea severity scores between subjects receiving zinc sulfate and subjects receiving placebo (P=0.284). Serum zinc levels were higher in subjects receiving zinc (P<0.001). Oral zinc sulfate was not associated with greater improvement in rosacea severity compared with placebo in this study. Additional studies are needed to determine what role oral zinc may have in the management of rosacea.
Introduction:
Acne is a chronic skin disorder of the pilosebaceous unit; it has a multifactorial pathogenesis. Propionibacterium acnes within the follicle is considered to be a triggering factor of inflammation in acne. Antibiotics have been the primary treatment against P. acnes for more than 40 years. However, a gradual increase in the prevalence of antibiotic-resistant strains of P. acnes has been observed.
Areas covered:
This review discusses the pathophysiology of antibiotic-resistant acne development. It focuses on strategies to minimize the development of resistance and, most importantly, confront the development of antibiotic-resistant acne. The literature search was conducted up to August 2010, using the search terms 'acne', 'antibiotic-resistant acne' and 'bacterial resistance'.
Expert opinion:
Antibiotic-resistant acne is a real phenomenon. Strategies to prevent and confront it should include not only the use of certain treatment regimens but also rational prescribing policies, combination therapies, use of antibacterial non-antibiotic agents and treatment options targeting all the pathogenetic components of acne. Benzoyl-peroxide-based treatment is the most evidence-based approach. Oral isotretinoin remains the most efficacious option for severe acne.
Zinc is a cofactor of many metalloenzymes explaining that it plays a crucial role in cell proliferation and also in the regulation of immune system. It has been shown by different data that it could play a crucial role not only in the regulation of adaptative immunity but also in innate immunity which plays a crucial role in skin.
In this article, we proposed an overview of published information in the literature, on zinc and cutaneous innate immunity.
At the basic level, we gave a synthesis of data related to zinc's cutaneous targets in innate immunity, and then at clinical level selected studies on cutaneous disorders where zinc could be a therapeutic approach and discussed the targets of zinc in these pathologies.
The specific activity of zinc salts on the innate immunity of the skin with different targets can explain why zinc is more specifically involved in cutaneous affection in which inflammation plays a particular important role, such as inflammatory acne, acrodermatitis enteropathica, hidradenitis suppurativa, folliculitis decalvans.
APC is a novel methionine-based zinc complex with antioxidants that has been used in acne as a nutritional supplement. This is based on the proven role of zinc and antioxidants in improving acne, specially the inflammatory lesions. The objectives of this study are to explore the efficacy, safety, and tolerability of APC in acne patients with mild to moderate facial acne vulgaris. In this exploratory trial, 48 patients were treated with oral APC thrice a day for 3 months followed by a 4-week treatment-free period. At the end of treatment (Week 12), there was a statistically significant improvement in the global acne count (p < 0.05), which began after 8 weeks (p < 0.05). Almost 79% (38/48) of the patients had 80-100% improvement. There was a significant reduction in pustules (8 weeks (p < 0.05) and 12 weeks (p < 0.001)), and papules and closed comedones (8 weeks (p < 0.05) and 12 weeks (p < 0.001)). Only two patients had side effects. The current data indicate that treatment with oral APC thrice daily for 12 weeks in patients with mild to moderate facial acne vulgaris is efficacious and well tolerated. As the onset of action is late, concomitant topical therapy can enhance the results.
With a double-blind technique, the effects of oral zinc and tetracyclines were compared in 37 patients with moderate and severe acne. No difference in effect between the treatments was seen and no side-effects were noted in any group. After 12 weeks of treatment, the average decrease in the acne score was about 70% in both groups.
Forty-eight patients participated in a 3-month double-blind study to compare the effect of orally administered zinc sulphate/citrate complex and tetracycline hydrochloride in acne vulgaris. Tetracycline significantly reduced the overall grade, and the number of non-inflamed lesions, papules and pustules by the third month. It also reduced significantly the non-inflamed lesions and papules at the end of the second month. In contrast, zinc therapy only had a significant effect on the pustules at the third month.
The results indicate that tetracycline is far superior to the zinc complex in patients with moderately severe acne.
Propionibacteria resistant to high concentrations of erythromycin [minimal inhibitory concentration (MIC) > or = 0.5 mg/ml] are now commonly isolated from the skin of antibiotic-treated acne patients. This double-blind study was carried out to assess the ability of 4% w/v erythromycin with and without 1.2% w/v zinc acetate to reduce the numbers of erythromycin-resistant propionibacteria in vivo, and also to monitor the acquisition of resistant strains de novo during therapy. Under laboratory conditions, erythromycin-resistant propionibacteria were shown to be as sensitive to zinc acetate as fully sensitive strains. In vivo, the erythromycin/zinc complex and erythromycin alone produced highly significant reductions in total propionibacteria (P < 0.001) and in the number of erythromycin-resistant strains (P < 0.001 at 8 weeks). After 12 weeks, resistant propionibacteria were reacquired, or acquired de novo, by three patients treated with erythromycin alone and four patients treated with the erythromycin/zinc complex. In contrast, changes in numbers of Micrococcaceae were slight and, after 12 weeks, erythromycin-resistant strains were predominant in both treatment groups. In vitro MIC determinations suggested that this finding might be explained by the exceptionally high degree of erythromycin resistance displayed by some staphylococcal strains (MIC > 4 mg/ml) and by the relative insensitivity of all staphylococcal strains to zinc acetate. Erythromycin with and without zinc was clinically effective, and both preparations produced significant reductions in acne grade, and inflamed and non-inflamed lesion counts (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
In addition to tetracyclines, zinc may constitute an alternative treatment in inflammatory lesions of acne.
To evaluate the place of zinc gluconate in relation to antibiotics in the treatment of acne vulgaris.
Zinc was compared to minocycline in a multicenter randomized double-blind trial. 332 patients received either 30 mg elemental zinc or 100 mg minocycline over 3 months. The primary endpoint was defined as the percentage of the clinical success rate on day 90 (i.e. more than 2/3 decrease in inflammatory lesions, i.e. papules and pustules).
This clinical success rate was 31.2% for zinc and 63.4% for minocycline. Minocycline nevertheless showed a 9% superiority in action at 1 month and one of 17% at 3 months, with respect to the mean change in lesion count. Regarding safety, the majority of the adverse effects of zinc gluconate and of minocycline concerned the gastrointestinal system and were moderate (5 dropouts with zinc gluconate and 4 with minocycline).
Minocycline and zinc gluconate are both effective in the treatment of inflammatory acne, but minocycline has a superior effect evaluated to be 17% in our study.
Efficacite′ du gluconate de zinc dans le traitement de lacne′ inflammatoire
- J Revuz
- P Amblard
- B Dreno
Revuz J, Amblard P, Dreno B, et al. Efficacite′ du
gluconate de zinc dans le traitement de lacne′
inflammatoire. Abstr Dermatol 1990; 77: 2-4.
Efficacite′ du gluconate de zinc dans le traitement de l'acne′ inflammatoire
- Revuz