Allergen content of popular chemical hair relaxers: A product analysis.

BACKGROUND: Chemical hair relaxers are widely utilized by black women, yet little research exists on the allergens present in these products. OBJECTIVE: This study aims to investigate allergen prevalence in the most popular chemical hair relaxers. METHODS: We analysed 41 products from five major retailers, identifying allergens through ingredient lists and comparing them to the 2020 American Contact Dermatitis Group Core allergen series. RESULTS: The most common contact allergens in chemical relaxers include propylene glycol, cetyl steryl alcohol, fragrance, D/L-a-tocopherol, tea tree oil and cocamidopropyl betaine. CONCLUSION: Understanding allergen exposure in products used by individuals with textured hair is needed for managing contact dermatitis in diverse populations. This analysis underscores the presence of potential allergens in hair relaxers, emphasizing the importance of dermatologists' awareness and patient scrutiny of ingredient lists.

Analysis of patch testing with cocamidopropyl betaine and its impurities in patients with intractable scalp dermatitis in a single clinic in Japan.

BACKGROUND: The allergen responsible for cocamidopropyl betaine (CAPB) allergies has been debated. OBJECTIVES: To investigate the sensitizing agents of CAPB, the patch test positivity rates of impurities were examined in Japanese patients with CAPB-related allergic contact dermatitis. MATERIALS AND METHODS: Thirty patients with scalp dermatitis and positive patch tests for CAPB and/or lauramidopropyl betaine (LAPB) were enrolled in this study. They were patch tested with the detergents that they had been using at the time of their first visit and with the impurities dimethylaminopropylamine (DMAPA) and lauramidopropyl dimethylamine (LAPDMA). RESULTS: The positivity rate in patch tests of the 37 detergents that the patients had been using was 78.4% (29/37). The positivity rates of DMAPA 1% pet., 1% aq. and 0.2% aq. were 32.1% (9/28), 14.3% (4/28) and 13.3% (4/30), respectively, whereas those of LAPDMA 0.1% and 0.05% were 30.0% (9/30) and 16.7% (5/30), respectively. Among the 30 patients, 6 exhibited positive results for both DMAPA and LAPDMA, 3 showed positive results for DMAPA alone and 6 produced positive results for LAPDMA alone. CONCLUSION: Patch tests produced an overall positivity rate for DMAPA, LAPDMA or both of 50.0% (15/30) in patients with scalp dermatitis and positive patch test results for CAPB and/or LAPB.

Betaine prevents cognitive dysfunction by suppressing hippocampal microglial activation in chronic social isolated male mice.

Chronic social isolation (SI) stress, which became more prevalent during the COVID-19 pandemic, contributes to abnormal behavior, including mood changes and cognitive impairment. Known as a functional nutrient, betaine has potent antioxidant and anti-inflammatory properties in vivo. However, whether betaine can alleviate the abnormal behavior induced by chronic SI in mice remains unknown. In this study, we investigated the efficacy of betaine in the treatment of behavioral changes and its underlying mechanism. Three-week-old male mice were randomly housed for 8 weeks in either group housing (GH) or SI. The animals were divided into normal saline-treated GH, normal saline-treated SI, and betaine-treated SI groups in the sixth week. The cognitive and depression-like behavior was determined in the eighth week. We found that long-term betaine administration improved cognitive behavior in SI mice but failed to prevent depression-like behavior. Moreover, long-term betaine administration inhibited hippocampal microglia over-activation and polarized microglia toward the M2 phenotype, which effectively inhibited the expression of inflammatory factors in SI mice. Finally, the protective effect of betaine treatment in SI mice might not be due to altered activity of the hypothalamic-pituitary-adrenal axis. Collectively, our findings reveal that betaine can improve SI-induced cognitive impairment, thus providing an alternative natural source for the prevention of memory loss caused by SI or loneliness.

[ANALYSIS OF PATCH TEST RESULTS USING COCAMIDOPROPYL BETAINE-RELATED SURFACTANTS].

BACKGROUND: A few previous studies have compared the patch test (PT) results obtained using different types of PT units. OBJECTIVES: This study aimed to compare PT results between the Patch Tester 'Torii' and Finn Chamber. METHODS: Thirty-four patients with intractable scalp dermatitis were enrolled in this study. PT were performed with three kinds of amphoteric surfactants, cocamidopropyl betaine (CAPB), high-concentration CAPB (h-CAPB), and lauramidopropyl betaine (LAPB), using both the Patch Tester 'Torii' and Finn Chamber, and the changes in the subjects' symptoms after they stopped using these surfactants were examined. RESULTS: Regarding the PT results for CAPB, h-CAPB, and LAPB, the results obtained with the Finn Chamber included a significantly lower frequency of irritant reactions (CAPB; p=0.003, h-CAPB; p=0.046, LAPB; p=0.002) than those obtained with the Patch Tester 'Torii'. However, there were no significant differences in the frequencies of positive reactions between the Patch Tester 'Torii' and Finn Chamber in each surfactant. The same tendency was seen in PT with LAPB (p=0.041) in 17 selected patients, who showed positive or doubtful reactions in PT performed with the surfactant-containing products they had used and whose symptoms 'markedly improved' or 'improved' after they stopped using these products. Among these surfactants, CAPB exhibited the highest positivity rate; however, the differences were not significant. CONCLUSION: In patients with intractable scalp dermatitis, PT of the abovementioned surfactants performed using the Finn Chamber were superior to those conducted using the Patch Tester 'Torii' because they resulted in fewer irritant reactions.

Postauthorization safety study of betaine anhydrous.

Patient registries for rare diseases enable systematic data collection and can also be used to facilitate postauthorization safety studies (PASS) for orphan drugs. This study evaluates the PASS for betaine anhydrous (Cystadane), conducted as public private partnership (PPP) between the European network and registry for homocystinurias and methylation defects and the marketing authorization holder (MAH). Data were prospectively collected, 2013-2016, in a noninterventional, international, multicenter, registry study. Putative adverse and severe adverse events were reported to the MAH's pharmacovigilance. In total, 130 individuals with vitamin B6 nonresponsive (N = 54) and partially responsive (N = 7) cystathionine beta-synthase (CBS) deficiency, as well as 5,10-methylenetetrahydrofolate reductase (MTHFR; N = 21) deficiency and cobalamin C (N = 48) disease were included. Median (range) duration of treatment with betaine anhydrous was 6.8 (0-9.8) years. The prescribed betaine dose exceeded the recommended maximum (6 g/day) in 49% of individuals older than 10 years because of continued dose adaptation to weight; however, with disease-specific differences (minimum: 31% in B6 nonresponsive CBS deficiency, maximum: 67% in MTHFR deficiency). Despite dose escalation no new or potential risk was identified. Combined disease-specific treatment decreased mean ± SD total plasma homocysteine concentrations from 203 ± 116 to 81 ± 51 µmol/L (p < 0.0001), except in MTHFR deficiency. Recommendations for betaine anhydrous dosage were revised for individuals ≥ 10 years. PPPs between MAH and international scientific consortia can be considered a reliable model for implementing a PASS, reutilizing well-established structures and avoiding data duplication and fragmentation.

[A CASE OF ALLERGIC CONTACT DERMATITIS CAUSED BY DETERGENTS CONTAINING COCAMIDOPROPYL BETAINE IN WHICH AN IMPURITY WAS THE POSSIBLE CAUSATIVE AGENT].

Cocamidopropyl betaine (CAPB) is an amphoteric surfactant. It has several functions, including producing effervescence and washing effects, and thus, it is used in many cleansing products, such as shampoo and liquid body cleansers. Recently, it has become clear that some impurities that arise during the manufacturing process can have sensitizing effects. Herein, we report a case of allergic contact dermatitis caused by detergents containing CAPB, in which an impurity was determined to be the possible causative agent by patch testing and chemical analysis.A 64-year-old Japanese female developed a skin rash on the hairlines of her forehead and nuchal region one month before her first visit to our clinic. Later, the rashes, which were composed of desquamative erythema, expanded to her face, neck, upper back, and chest. Patch tests produced positive results for a shampoo and liquid body cleanser (1% aq.) that she had used as well as for CAPB (1% aq.); lauramidopropyl betaine (LAPB) (1% aq.); and lauramidopropyl dimethylamine (LAPDMA) (0.05% aq.), which is an impurity of CAPB. The rashes resolved completely after we instructed her to use products without CAPB and LAPB. When issuing such instructions, clinicians should have correct knowledge about surfactants, such as the differences between cosmetic ingredient names and quasi-drug ingredient names.

Analytic Approaches for the Treatment of Hyperhomocysteinemia and Its Impact on Vascular Disease.

Homocysteine is an intermediary metabolite in the methionine cycle. Accumulation of homocysteine is caused either by mutation of relevant genes or by nutritional depletion of related vitamin(s). This review covers the historical background of hyperhomocysteinemia in which indispensable subjects in relation to underlying pathophysiological processes are discussed with the view of metabolism and genetics of folate and methionine cycles. This review emphasizes the unique role of homocysteine that is clearly distinct from other risk factors, particularly cholesterol in the development of vascular disease. The critical issue in understanding the role of homocysteine is the relation with plasma folic acid. The majority of subjects with homocysteine > 15 µmol/L exhibit plasma folate < 9 nmol/ L, indicating that depletion of folate is the main cause of hyperhomocysteinemia irrespective of the presence or absence of vascular disease. Furthermore, only the group of subjects with homocysteine levels > 15 µmol/L demonstrated a higher prevalence of vascular disease. Analytic approaches to treat hyperhomocysteinemia are discussed in which stepwise administration with nutritional doses of folic acid, 5-methyitetrahydrofolate (5-MTHF), and betaine is provided singly or by combined manner based on clinical and laboratory evaluations. Whether correction of hyperhomocysteinemia is able to prevent the development of homocysteine-associated vascular disease remains an unresolved issue. The review discussed a biochemical and mechanistic approach to resolve questions involved in the relation between homocysteine and the development of atherosclerotic vascular disease.

Safety Assessment of Alkyl Betaines as Used in Cosmetics.

The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of 11 alkyl betaines as used in cosmetics. These ingredients are reported to function as hair and skin conditioning agents, antistatic agents, surfactants-cleansing agents, and viscosity-increasing agents in cosmetic products. Although there are data gaps, the shared chemical core structure, similar functions and concentrations of use in cosmetics, and the expected similarities in physicochemical properties enabled grouping these ingredients and reading across the available toxicological data to support the safety assessment of each individual compound in the entire group. The Panel concluded alkyl betaines were safe as cosmetic ingredients in the present practices of use and concentration, when formulated to be nonirritating.

Antiseptic mouthwashes could worsen xerostomia in patients taking polypharmacy.

OBJECTIVE: Polypharmacy is a common cause of xerostomia. This study aimed to investigate whether xerostomia could be an adverse drug event of mouthwashes, when they are used for longer than 2 weeks by patients taking polypharmacy. MATERIALS AND METHODS: This cross-sectional observational study included 120 hospitalized patients (60 middle-aged and 60 elderly patients), taking polypharmacy (≥4 drugs daily) and at risk of drug-induced xerostomia. Xerostomia was assessed by questioning participants. RESULTS: A total of 62.5% of patients complained of xerostomia. In the middle-aged group (mean age=44.0 (8.7) years; 35.0% women) xerostomia seemed independently associated to mouthwashes, at the limit of significance (OR=5.00, 95% CI=0.99-25.3, p=0.052). Active principles in mouthwashes were mainly quaternary ammonium compounds (91.9%). Mouthwashes may disturb the healthy balance of the biofilm moisturizing the oral mucosa. The biofilm contains mucins, salivary glycoproteins with oligosaccharides side chains able to sequester water and endogenous bacteria surrounded by a glycocalyx. Oral bacteria are fully susceptible to quaternary ammonium (chlorhexidine, hexetidine, cetylpyridinium chloride) and to other antiseptics used in mouthwashes, such as betain, resorcin, triclosan, essential oils and alcohol. However, caregivers currently recommend such dental plaque control products to patients suffering from xerostomia in order to reduce the risk of caries and periodontitis. CONCLUSION: This study is the first report that use of antiseptic mouthwashes for more than 2 weeks could worsen xerostomia in patients taking polypharmacy. Oral care protocols should avoid this iatrogenic practice, particularly when xerostomia alters the quality-of-life and worsens malnutrition.

Betaine eliminates CFA-induced depressive-like behaviour in mice may be through inhibition of microglia and astrocyte activation and polarization.

Chronic pain can induce not only nociceptive but also depressive emotions. A previous study demonstrated that betaine, a commonly used nutrient supplement, has an anti-nociceptive effect, but whether betaine can alleviate chronic pain-induced depressive emotion is elusive. Our current study found that betaine administration significantly eliminated complete Freund's adjuvant (CFA)-induced pain-related depressive-like behaviour. Mechanistically, betaine treatment inhibited microglia and astrocyte activation. Furthermore, betaine significantly promoted the transition of microglia from the M1 to the M2 phenotype, as well as the transition of astrocytes from the A1 to the A2 phenotype. Additionally, the release of pro-inflammatory factors such as IL-18, IL-1ß and IL-6 and anti-inflammatory factors such as IL-10 in the hippocampus induced by CFA were also reversed by betaine administration. Overall, betaine has therapeutic effects on pain-related depressive-like phenotypes caused by CFA, possibly through altering the polarization of microglia and astrocytes to reduce neuroinflammation.

Maternal methyl-donor supplementation induces prolonged murine offspring colitis susceptibility in association with mucosal epigenetic and microbiomic changes.

Developmental epigenetic changes, such as DNA methylation, have been recognized as potential pathogenic factors in inflammatory bowel diseases, the hallmark of which is an exaggerated immune response against luminal microbes. A methyl-donor (MD) diet can modify DNA methylation at select murine genomic loci during early development. The components of the MDs are routinely incorporated into prenatal human supplements. Therefore, we studied the effects of maternal MD supplementation on offspring colitis susceptibility and colonic mucosal DNA methylation and gene expression changes in mice as a model. Additionally, we investigated the offspring mucosal microbiomic response to the maternal dietary supplementation. Colitis was induced by dextran sulfate sodium. Colonic mucosa from offspring of MD-supplemented mothers following reversal to control diet at weaning was interrogated by methylation-specific microarrays and pyrosequencing at postnatal days 30 (P30) and P90. Transcriptomic changes were analyzed by microarray profiling and real-time reverse transcription polymerase chain reaction. The mucosal microbiome was studied by high throughput pyrosequencing of 16S rRNA. Maternal MD supplementation induced a striking susceptibility to colitis in offspring. This phenotype was associated with colonic mucosal DNA methylation and expression changes. Metagenomic analyses did not reveal consistent bacteriomic differences between P30 and P90, but showed a prolonged effect of the diet on the offspring mucosal microbiome. In conclusion, maternal MD supplementation increases offspring colitis susceptibility that associates with persistent epigenetic and prolonged microbiomic changes. These findings underscore that epigenomic reprogramming relevant to mammalian colitis can occur during early development in response to maternal dietary modifications.

The triggering role of allergic contact dermatitis in discoid lupus erythematosus.

BACKGROUND: The onset and exacerbations of discoid lupus erythematosus (DLE) can be precipitated by several factors like needling, scratches, trauma, X-rays, heat, cold, pressure, tattooing, scars, allergic and irritant dermatitis and inflammatory dermatoses. OBJECTIVE: To investigate the role of allergic contact dermatitis (ACD) in devolopment and triggering of the lesions of DLE. MATERIALS AND METHODS: This study was performed on 30 patients with DLE. European baseline series and cosmetic patch test series were used. At least 1+ reaction was accepted as meaningful. RESULTS: Twenty-three (76.7%) of 30 DLE patients and 16 (40%) of 40 control group patients were allergic to at least one allergen on standard patch test series. The difference between the groups were found statistically significant. Seventeen (56.7%) of 30 DLE patients and 6 (15%) of 40 control group patients were allergic to at least one allergen on cosmetic patch test series. The difference between the groups were statistically significant. The most sensitized allergens in both the groups were nickel sulphate, paraphenylen diamine, potassium dichromate from standard patch test series; quaternium 15, cocamidopropyl betain from cosmetic patch test series, in order. CONCLUSION: This study is distinctive since it is the first study to determine the eliciting role of ACD on DLE by imposing standard and cosmetic patch test series on DLE and control group patients. Worldwide, there is no study based on this subject. In the DLE group, the results of sensitization on standard and cosmetic patch test series were higher and statistically significant. Larger studies are required to reveal the exact role.

Occupational contact allergy to cocamidopropyl betaine and its impurities.

BACKGROUND: Contact allergy to cocamidopropyl betaine has been attributed to its impurities dimethylaminopropylamine and cocamidopropyl dimethylamine. OBJECTIVES: To describe patients with positive patch test reactions to cocamidopropyl betaine-related compounds in an occupational dermatology clinic. METHODS: We reviewed the 2002-2009 patch test records at the Finnish Institute of Occupational Health for allergic reactions to cocamidopropyl betaine, dimethylaminopropylamine, cocamidopropyl dimethylamine, and oleamidopropyl dimethylamine. Results. Irritant reactions to at least one of the test substances were seen in 39% of the 1092 patients tested. Fifteen (1.3%) patients showed allergic reactions: 13 to cocamidopropyl dimethylamine, 11 to dimethylaminopropylamine, 8 to oleamidopropyl dimethylamine, and 2 to cocamidopropyl betaine. Concomitant reactions to cocamidopropyl dimethylamine, dimethylaminopropylamine and oleamidopropyl dimethylamine were common. Ten of the 15 patients were diagnosed with occupational allergic contact dermatitis caused by cocamidopropyl betaine-related compounds. The sources of occupational exposure included hair care products, hair colours, perm wave solutions, and liquid soaps. Multiple contact allergies and exposure to several irritant factors were common, and all patients had hand eczema. CONCLUSIONS: Patch test reactions to cocamidopropyl betaine-related compounds are difficult to interpret, owing to extremely common irritant reactions. Cocamidopropyl betaine itself is probably not an allergen. Occupational allergic contact dermatitis caused by cocamidopropyl betaine-related compounds is relatively rare and, unlike non-occupational cocamidopropyl betaine-related allergy, typically manifests as hand dermatitis.

Final report of the Cosmetic Ingredient Review Expert Panel on the safety assessment of cocamidopropyl betaine (CAPB).

Cocamidopropyl betaine (CAPB) and related amidopropyl betaines are zwitterions used mainly as surfactants in cosmetics. These cosmetic ingredients are similar in their chemistry, in particular with respect to the presence of 3,3-dimethylamino-propylamine (DMAPA) and fatty acid amidopropyl dimethylamine (amidoamine) impurities, which are known as sensitizers. The CIR Expert Panel concluded that because these ingredients present no other significant toxicity, when formulated to be nonsensitizing (which may be based on a quantitative risk assessment), these ingredients are safe for use as cosmetic ingredients in the practices of use and concentration of this safety assessment.

Pathogenic Mechanisms of Trimethylamine N-Oxide-induced Atherosclerosis and Cardiomyopathy.

Trimethylamine N-oxide (TMAO) is a gut microbiota metabolite derived from trimethylamine- containing nutrient precursors such as choline, L-carnitine, and betaine, which are rich in many vegetables, fruits, nuts, dairy products, and meats. An increasing number of clinical studies have demonstrated a strong relationship between elevated plasma TMAO levels and adverse cardiovascular events. It is commonly agreed that TMAO acts as an independent risk factor and a prognostic index for patients with cardiovascular disease. Although most animal (mainly rodent) data support the clinical findings, the mechanisms by which TMAO modulates the cardiovascular system are still not well understood. In this context, we provide an overview of the potential mechanisms underlying TMAO-induced cardiovascular diseases at the cellular and molecular levels, with a focus on atherosclerosis. We also address the direct effects of TMAO on cardiomyocytes (a new and under-researched area) and finally propose TMAO as a potential biomarker and/or therapeutic target for diagnosis and treatment of patients with cardiovascular disease.

Is cocamidopropyl betaine a contact allergen? Analysis of network data and short review of the literature.

BACKGROUND: There is no general agreement on whether cocamidopropyl betaine (CAPB) is a skin sensitizer. OBJECTIVE: To examine the evidence for CAPB being a (non-)sensitizer. METHODS: This was a retrospective analysis of data on patch testing with CAPB 1% aqua collected by the Information Network of Departments of Dermatology from 1996 to 2009, with a focus on the patch test reaction profile, and demographic and clinical features of CAPB positives, supplemented by a literature review. RESULTS: Eighty-three thousand eight hundred and sixty-four patients were patch tested with CAPB 1% aqua, yielding 2.16% [95% confidence interval (CI) 2.06-2.26%] positive (2.03% + and 0.13% + + /+ + + ) and 4.6% non-allergic reactions. Thus, the reaction index was-0.368 and the positivity ratio was 94.2%. Reproducibility on synchronous patch testing (n = 6534) was poor [Cohen's kappa: 0.29 (95% CI 0.25-0.32)] and results upon retesting (n = 1157) were almost non-reproducible [kappa: 0.12 (95% CI 0.05-0.19]. Multifactorial logistic regression analysis revealed an increased risk associated with being male and aged ≥40 years, with atopic dermatitis, with scalp dermatitis, with being a hairdresser, and with a 48-hr patch test application. When only + + or + + + reactions were used as a conservative outcome, only the elevated risk in males and in patients with atopic dermatitis remained significant. CONCLUSION: The vast majority of positive reactions to CAPB are presumably false positive. Allergic reactions are very rare. This would support the notion of CAPB being 'not a significant skin sensitizer', in line with current classification systems.

Betaine Supplementation Moderately Increases Total Cholesterol Levels: A Systematic Review and Meta-Analysis.

Betaine is used to lower elevated plasma homocysteine levels, which are a risk factor for cardiovascular diseases (CVD). However, some studies have shown that betaine may have a negative effect on blood lipids. Betaine supplementation is becoming more and more common, but the relationship between betaine supplementation and blood lipoprotein levels are unclear. The purpose of the study described here was thus to perform a meta-analysis of randomized placebo-controlled trials on the effects of betaine supplementation at a daily dose of at least 4 g on blood lipids in adults. Six randomized controlled trials published between 2002 and 2018 were identified. All six studies used adult participants supplemented with at least 4 g/d of betaine for six to twenty-four weeks. A meta-analysis was carried out using a random-effects model, and the overall effect size was calculated for changes in plasma total cholesterol (TC), HDL cholesterol, LDL cholesterol, and triglycerides (TG). The pooled estimate of the effects of betaine supplementation compared to placebo on TC was 0.34 mmol/L (95% CI: 0.02, 0.65), p = 0.0352. No significant effect was observed for LDL, HDL, or TG. Supplementation with at least 4 g/d of betaine for a minimum of six weeks may moderately increase plasma TC, which might be important in the context of cardiovascular health.

Betaine for nonalcoholic fatty liver disease: results of a randomized placebo-controlled trial.

UNLABELLED: Based on animal studies and pilot studies in humans, betaine, a methyl donor for the remethylation of homocysteine, may be a therapeutic agent for nonalcoholic steatohepatitis (NASH). We evaluated the safety and efficacy of betaine for patients with NASH and whether betaine positively modified factors postulated to be "second hits" and underlying mechanisms of NASH. We conducted a randomized placebo-control study of 55 patients with biopsy-proven NASH who received either oral betaine (20 g daily) or placebo for 12 months. Pre- and posttreatment variables were analyzed using the paired t test or Wilcoxon rank test. Treatment groups were comparable at baseline. Of the 35 patients (17 betaine, 18 placebo) who completed the study, 34 patients (16 betaine, 18 placebo) underwent posttreatment liver biopsy. Patients randomized to betaine had a decrease in steatosis grade. No intra- or intergroup differences or changes in nonalcoholic fatty liver disease activity score or fibrosis stage were noted. Elevations of insulin, glucose, and proinflammatory cytokines and the reduced antioxidant status noted in NASH patients did not improve with betaine therapy. The antiinflammatory agent adiponectin was significantly reduced in both groups and did not change with therapy. Lastly, S-adenosylhomocysteine was approximately twice normal and was not reduced by betaine therapy. CONCLUSION: Compared to placebo, betaine did not improve hepatic steatosis but may protect against worseningsteatosis [corrected]. High-dose betaine supplementation failed to reduce S-adenosylhomocysteine and did not positively affect any of the second hit mechanisms postulated to contribute to NASH that we studied. Although betaine has been proven effective in treating hepatic steatosis in several animal models, translating novel therapeutic options noted in animal studies to humans with NASH will prove challenging.