원료 사전 탐색/caffeine/CAFFEINE
Tier 1 Monograph · SSOT 15 FieldsRaw .md (GEO) ↗
합성 (Synthetic)

CAFFEINE

식약처 한글 표준명: 카페인
피부컨디셔닝제향료
[식약처 공정서 기원 및 정의] 이 원료는 다음의 구조를 갖는 헤테로사이클릭 유기화합물이다.
[EU CosIng Official Definition] Caffeine is the heterocyclic organic compound that conforms to the formula
결론 선행 Executive Regulatory & Safety Fact BoxAEO / GEO CITATION ANCHOR

화장품에서 카페인 (CAFFEINE)의 글로벌 배합 한도와 핵심 효능·처방 기준은 무엇인가요?

카페인(표준 INCI: CAFFEINE, CAS 번호: 58-08-2)은 화장품 처방에서 주로 피부컨디셔닝제, 향료 목적으로 배합되는 핵심 원료입니다. 한국 식약처(미규제) 및 유럽 CosIng(미규제) 등 6대 권역 법정 기준 하에 관리되며, 통상 0.1–1%(적정 pH 4–8) 범위에서 안정적으로 처방됩니다.

7대 갈래 국가별·용도별 공식 전성분 라벨 표기명 매트릭스

각국 1차 법원 고시 정본 · 기계번역·임의 음차 0건
7-Track Official Statutory Label Names for CAFFEINE
국가·규제 트랙공식 고시 전성분 표기명원클릭 복사
① 한국 (MFDS 화장품 한글 표준명)카페인
② 한국 구명칭 (개정 전 이력 · 301 리다이렉트)——
③ 유럽 (EU CosIng EC 1223/2009)CAFFEINE
④ 미국 일반화장품 (US PCPC / MoCRA INCI)CAFFEINE
⑤ 미국 OTC (FDA Active Ingredient Monograph)— (비-OTC 일반 화장품 원료)—
⑥ 중국 (NMPA IECIC 표준 중문명)咖啡因
⑦ 일본 일반화장품 / 의약부외품 (JCIA / MHLW)カフェイン · [QD: 無水カフェイン]

Layer 1 — 글로벌 6대 권역 법정 배합 한도 및 규제 상태

Layer 1 Statutory Regulatory Limits Across 6 Regions for CAFFEINE
권역규제 상태배합 한도제한 조건 및 1차 법원 출처
일본 (MHLW)제한≤ 2%
—
Source: 化粧品に配合可能な医薬品の成分について(薬食審査発第0524001号) 별첨 「承認化粧品成分の範囲」
⚠️ 참조용 안내 (법적 면책 공지): 이 사전의 성분명·규제 한도·배합 가이드는 연구·개발 참조용으로만 제공됩니다. 각국 고시 개정 시차나 데이터 오기·누락이 있을 수 있으므로, 실제 제품 처방·라벨 표기·인허가 전에는 반드시 관할 기관(식약처 등)의 최신 공식 고시 원문을 직접 확인하시기 바라며, 본 사전의 정보를 잘못 사용하여 발생하는 문제에 대해 운영 주체는 법적 책임을 지지 않습니다.
제형군별 사분위수(Min–Q1–Median–Q3–Max) 분포 그래프

Layer 3 제형군별 통상 배합 농도(%) 레인지 & Layer 1 법정 한도 대조

법정 최대 한도: 2%
O/W · W/O 에멀전·크림n=5
Min 0.1% · Q1 0.5% · Median 1% · Q3 1% · Max 1%
O/W · W/O 에멀전·크림 — 유화 로션·크림 제형 구조 형성 및 피부 컨디셔닝
공식 검증 원천: Global Starter Formulation Library Statistical Distribution (n=5, GRANT 3 · EVONIK 2) (cir_safety) · GRANT 3 · EVONIK 2
권장 중앙값: 1%

Layer 3 — 제형군별 통상 배합 농도(n≥5 사분위수) & 물리화학·상용성 가이드

Layer 3 Formulation Concentration Quartiles by Product Category for CAFFEINE
제형군 분류Min – Q1 – Median – Q3 – Max (%)처방 역할 및 기전Source ID
제형군 B — 유화 로션 · 에멀전 · 크림 (O/W · W/O)0.1% · 0.5% · 1% · 1% · 1%유화 로션·크림 제형 구조 형성 및 피부 컨디셔닝Global Starter Formulation Library Statistical Distribution (n=5, GRANT 3 · EVONIK 2)
피부 투과 과학 시각화 (Bos & Meinardi 500 Dalton Rule)MW: Macro/Complex · LogP: N/A

각질층 장벽 투과 깊이 & 바이오 스피큘 경피전달(DDS) 시뮬레이션

각질층 (Stratum Corneum · 10~20 µm)500 Dalton 장벽 (고분자·친수성 성분 차단)생존 표피층 (Viable Epidermis · 50~100 µm)멜라닌세포 · 각질형성세포 타깃 (미백·장벽·턴오버)진피 유두층 (Papillary Dermis · 150~300 µm)섬유아세포 콜라겐 I/III · 엘라스틴 · PDRN 재생 타깃표피~상부 진피 확산 (<500 Da)
분자량(MW) & 친유성(LogP) 투과 판정
저분자 영역 (320 Da ≤ 500 Da) — 각질층 수동 확산 가능

단독 도포 시 각질층 세포간 지질(Brick & Mortar) 경로를 통해 확산됩니다. 500 Dalton 이상 친수성 분자는 각질층 표면에 주로 머물러 보습·보호막 역할을 수행합니다.

예상 도달 깊이
40–90 µm
권장 전달 시스템
Polyol Enhancer / Serum
계면화학 · pH · 열역학 공정 시각화

pH 안정성 스펙트럼(0~14) · 가열 한계 게이지 · HLB 콜로이드 상거동

Water or glycol phase soluble/dispersible
적정 처방 pH 안전 윈도우 (pH 0 ~ 14 스펙트럼)pH 4.0 – 8.0
0245.5791114

권장 구간 밖(pH < 4 또는 pH > 8)에서는 가수분해·점도 저하·이온 탈리 위험이 증가합니다.

공정 가열 한계 온도 (Max Process Temp)≤ 50°C
25°C45°C60°C75°C85°C100°C

최대 50°C 가열 공정에서 열적 안정성이 유지됩니다.

계면활성·유화 HLB 스펙트럼 (0 ~ 20) & 미셀/액정 배열 시뮬레이터
O/W 수중유형 미셀 에멀전 (수분 크림·로션)
HLB 11.5
W/O (3–6)Lamellar (8–10.5)O/W Emulsion (11–15)Solubilizer (15–19)O/W Droplet
생화학 신호전달 경로 (Biochemical Pathway Map)

세포·분자 타깃 작용 기전 플로우 다이어그램

1. 각질층·표피 작용→ 촉진·활성 (Activation)
각질층 세포간 지질 & 수분 결합 네트워크
→
경피수분손실(TEWL) 억제 및 피부결 개선
2. 염증 매개체 조절⊣ 억제·차단 (Inhibition)
외부 자극 유도 산화 스트레스(ROS) 및 사이토카인
⊣
피부 진정 및 항상성 유지
처방 온톨로지 네트워크 그래프

권장 시너지(🟢 실선) & 배합 금기·주의(🔴 점선) 인터랙티브 관계도

+ GLYCERIN+ CAPRYLIC/CAPRIC TR…+ TOCOPHEROL✕ 처방 내 극단적 pH 조건 및 고농도…CAFFEINE
노드 인터랙션 가이드

🟢 초록색 시너지 원료 노드를 클릭하면 해당 원료 모노그래프로 즉시 이동하며, 🔴 붉은색 점선 노드를 클릭하면 화학적 상충(석출·변색·실활) 메커니즘을 표시합니다.

대표 상용명 참고 (상표법 제90조 제1항 제2호 설명적 표기)
CAFFEINE

상용명 표기는 상표법 제90조 제1항 제2호에 의거하여 연구원에게 원료 등급·규격을 설명하기 위한 참고용이며, 각 상표의 권리는 해당 원료사에 귀속됩니다.

학술·독성·제형 종합 요약 (Tier 1~3 탄력 요약)

Tier 1 Synthesis

이 원료에 매칭된 PubMed 동료심사 논문 초록과 공인 독성 보고서만으로 작성된 학술 요약입니다.

■ [1. 화학적 정체성 및 규격 (Chemical Identity & Standard Nomenclature)] - 표준명: 카페인 | INCI: CAFFEINE | CAS No.: 58-08-2 | EC No.: 200-362-1 - 기원 및 분류: SYNTHETIC | 주요 기능: 피부컨디셔닝제, 향료 - 물리화학 스펙: 분자식 복합 조성이거나 단일 화학식 미지정 | 분자량 고분자/복합물(Polymer/Complex) | 친수/친유 밸런스 특화 | 이온성: non-ionic | CosIng/MFDS 등재 - 7대 권역 공식 라벨 표기: KR [카페인] · EU [CAFFEINE] · US [CAFFEINE] · CN [咖啡因] · JP [カフェイン] · JP의약부외품 [無水カフェイン] ■ [2. 피부과학적 작용 기전 및 제형 내 역할 (Mechanism of Action & Function)] - 이 원료는 다음의 구조를 갖는 헤테로사이클릭 유기화합물이다. 물리화학적 분류상 기원(synthetic)에 기반하여 피부 장벽 및 제형 매트릭스 내에서 고유한 기능(피부컨디셔닝제, 향료)을 수행하며, 계면 안정화·보습·피부 컨디셔닝 또는 유효성분 전달에 기여합니다. ■ [3. 글로벌 6대 권역 법정 규제 및 안전성 한도 (Layer 1 & Layer 2 Regulatory Matrix)] - 6개국 요약: KR: NONE | EU: NONE | US: NONE | CN: ALLOWED | JP: RESTRICTED | ASEAN: NONE (중국 IECIC(2025) 등재번호 4077 (咖啡因)) - [JP / COMPOSITION / limited] (최대 2%): - 공인 안전성·역사적 사용 농도(Layer 2): 제형 목적 및 GMP 안전성 평가 범위 내 적량(QS) 사용 ■ [4. 제형군별 통상 배합 가이드 (Layer 3-A Formulation Dosage Guide)] - [emulsion_cream] 권장 범위: 0.1 ~ 1.0% (중앙값 1.0%, 근거: Global Starter Formulation Library Statistical Distribution (n=5, GRANT 3 · EVONIK 2)) — 유화 로션·크림 제형 구조 형성 및 피부 컨디셔닝 ■ [5. 연구원 공정 설계 · 안정성 · 배합 금기 (Layer 3-B Process & Compatibility)] - 투입 공정(Phase): Water Phase or Cool-down Phase (< 45°C) - 적정 pH 구간: pH 4.0 ~ 8.0 | 공정 내열 온도: 최대 50°C | 전해질(염) 내성: MEDIUM - 배합 주의/금기: 처방 내 극단적 pH 조건 및 고농도 전해질과의 상용성 사전 확인 권장 - 시너지 추천 원료: GLYCERIN, CAPRYLIC/CAPRIC TRIGLYCERIDE, TOCOPHEROL | 참고 상용 원료명: CAFFEINE ■ [6. 학술 논문 및 공인 문헌 근거 (Peer-Reviewed Literature & Compendia)] - PMID 23075568 (2013, Skin Pharmacol Physiol): Caffeine's mechanisms of action and its cosmetic use - PMID 40820949 (2025, J Cosmet Dermatol): A Novel Approach Against Male Pattern Hair Loss With Topical Dimethylglycine Sodium Salt (DMG-Na) and Caffeine: Efficacy - PMID 26004004 (2015, Int J Pharm): Topical and transdermal delivery of caffeine

근거 동료심사 학술 논문 (미국 NIH PubMed) (18)

Caffeine's mechanisms of action and its cosmetic use [PMID: 23075568 · 2013]
Herman A, Herman AP · Skin Pharmacol Physiol (2013)

Caffeine is being increasingly used in cosmetics due to its high biological activity and ability to penetrate the skin barrier. This alkaloid is frequently used as a hydrophilic model substance in human and animal skin penetration as well as different synthetic membrane using Franz diffusion cell experiments. The commercially available topical formulations of caffeine normally contain 3% caffeine. As for a cosmetic purpose, caffeine is used as an active compound in anti-cellulite products because it prevents excessive accumulation of fat in cells. This alkaloid stimulates the degradation of fats during lipolysis through inhibition of the phosphodiesterase activity. Caffeine has potent antioxidant properties. It helps protect cells against the UV radiation and slows down the process of photoaging of the skin. Moreover, caffeine contained in cosmetics increases the microcirculation of blood in the skin and also stimulates the growth of hair through inhibition of the 5-&#x3b1;-reductase activity.

A Novel Approach Against Male Pattern Hair Loss With Topical Dimethylglycine Sodium Salt (DMG-Na) and Caffeine: Efficacy of a 24-Week, Double-Blind, Randomized, Placebo-Controlled Trial [PMID: 40820949 · 2025]
Celleno L, Bussoletti C, Tolaini MV, Rossi A, Ala L, Becker M, V&#xf6;lker JM, Wiesche ESZ · J Cosmet Dermatol (2025)

Male pattern hair loss is the most common form of hair loss in men, occurring in specific patterns. Contributing factors include hormonal changes, stress, malnutrition, and insufficient blood microcirculation. Topical applied dimethylglycine sodium salt (DMG-Na) has been identified to increase skin microcirculation by activating endothelial nitric oxide synthase and inducing nitric oxide production. Given the importance of sufficient microcirculation on hair growth, the goal of this study was to evaluate the effectiveness of topically applied DMG-Na in combination with caffeine against male pattern hair loss. A 24-week, double-blind, randomized, placebo-controlled trial was conducted on 154 men with male pattern hair loss, treated with a DMG-Na and caffeine-containing shampoo or the corresponding placebo. The primary efficacy parameter was the change in the number of hairs pulled via hair pull test from baseline to 6&#x2009;months of daily product application. Clinical efficacy was further evaluated via phototrichogram analysis on a subgroup of 30 subjects. The decreased number of hairs pulled during the hair pull test after 6&#x2009;months of active shampoo application was significantly higher compared to the placebo (-2.8&#x2009;&#xb1;&#x2009;1.6 vs. 0.6&#x2009;&#xb1;&#x2009;2.2; p&#x2009;&lt;&#x2009;0.001), with no reported adverse events. Phototrichogram results showed an increase in the number of hairs, hair density, and percentage of anagen hairs after 6&#x2009;months of active shampoo usage (p&#x2009;&lt;&#x2009;0.001). The clinical efficacy of this novel DMG-Na and caffeine-containing shampoo demonstrates significant potential against male pattern hair loss, offering promising results without any undesirable side effects.

Topical and transdermal delivery of caffeine [PMID: 26004004 · 2015]
Luo L, Lane ME · Int J Pharm (2015)

Caffeine is administered topically and transdermally for a variety of pharmaceutical and cosmetic applications and it is also used as a model hydrophilic compound in dermal risk assessment studies. This review considers the physicochemical and permeation properties of caffeine with reference to its delivery to and through the skin. Since it has been used as a model compound the findings have implications for the delivery of many hydrophilic compounds having similar properties. Various passive and active formulation strategies to promote enhanced skin permeation of caffeine are considered. Models to study percutaneous caffeine penetration are also discussed in detail.

Caffeine and Its Pharmacological Benefits in the Management of Androgenetic Alopecia: A Review [PMID: 32599587 · 2020]
V&#xf6;lker JM, Koch N, Becker M, Klenk A · Skin Pharmacol Physiol (2020)

Caffeine, particularly after ingestion, is well known to exert various pharmacological effects. A growing body of evidence implicates the ingestion of caffeine with beneficial effects on several diseases. The easy penetration of caffeine across the skin barrier and into human skin makes caffeine an ideal compound for topical application. Hair loss is known to negatively affect the quality of life and predispose to depression and anxiety. Androgenetic alopecia (AGA) is the most common type of hair loss in both men and women. To date, only few approved drug-based treatments for AGA exist, and these are inevitably associated with side effects. Therefore, the development of topical treatments based on well-tolerated natural ingredients such as caffeine to alleviate hair loss may provide a much-needed alternative to drug-based approaches.

Challenges of nanotechnology in cosmetic permeation with caffeine [PMID: 34105652 · 2021]
Vogel EM, Bronoski M, Marques LLM, Cardoso FAR · Braz J Biol (2021)

The evolution of beauty market and personal care is constant in Brazil as well in the rest of the world. Technological advances have brought up nanotechnology to the cosmetological field, employing active principles at atoms enveloped by vesicles, in order to take the active principle precisely to the target tissue to optimize the results achieved because of the considerable ease to cross skin barriers. Manufacturing of nanotechnology cosmetics is confronted with low absorption capacity. One of the many active principle found in cosmetic industry is caffeine, a pseudoalkaloid from the xanthine group used as a stimulant with the mechanism of the lipolytic action. This active is widely used in &#x200b;&#x200b;a esthetics and cosmetics field in treatments involving dysfunctions such as localized fat and fibroedema geloid. To work out perfectly, the principle active need to interact and create a set of factors that includes lipolysis intensification. The caffeine encapsulation in gel-based nanocosmetics has the purpose of taking this active up to the adipocyte, the target cell, for mentioned dysfunctions treatment. Thus, we aim to present a review of how has been, the use of caffeine in the production of cosmetics.

Effect of caffeine on UVB-induced carcinogenesis, apoptosis, and the elimination of UVB-induced patches of p53 mutant epidermal cells in SKH-1 mice [PMID: 18179623 · 2008]
Conney AH, Kramata P, Lou YR, Lu YP · Photochem Photobiol (2008)

Oral administration of green tea or caffeine to SKH-1 mice during UVB irradiation for several months inhibited the formation of skin cancer. Similar effects were observed when green tea or caffeine was given to tumor-free UVB-initiated mice with a high risk of developing skin tumors in the absence of further UVB irradiation (high risk mice). Mechanistic studies indicated that topical application of caffeine stimulated UVB-induced apoptosis as well as apoptosis in UVB-induced focal hyperplasia and tumors in tumor-bearing mice. Oral or topical administration of caffeine enhanced the removal of patches of epidermal cells with a mutant form of p53 protein that appeared early during the course of UVB-induced carcinogenesis, and oral administration of caffeine altered the profile of p53 mutations in the patches. In additional studies, topical application of caffeine was shown to have a sunscreen effect, and topical application of caffeine sodium benzoate was more active than caffeine as a sunscreen and for stimulating UVB-induced apoptosis. Caffeine sodium benzoate was also highly active in inhibiting carcinogenesis in UVB-pretreated high risk mice. Our studies indicate that caffeine and caffeine sodium benzoate may be useful as novel inhibitors of sunlight-induced skin cancer.

Differential Time-of-Day Effects of Caffeine Capsule and Mouth Rinse on Physical Performance and Volleyball-Specific Skills in Adolescent Male Volleyball Players [PMID: 42196973 · 2026]
Amor SB, Dhahbi W, Souaifi M, Ceylan H&#x130;, Padulo J, Vando S, Ceylan NB, Muntean RI, Souissi N · Nutrients (2026)

This study compared the acute effects of caffeine capsule ingestion and caffeine mouth rinsing on physical performance and volleyball-specific skills at different times of day in trained adolescent male volleyball players. Twenty-four well-trained male volleyball players (age: 16.9 &#xb1; 0.7 years) completed a randomized, double-blind, placebo-controlled crossover study involving three supplementation conditions, caffeine capsule (CAFcap, 3 mg&#xb7;kg -1 ), caffeine mouth rinse (CAFrinse, 3 mg&#xb7;kg -1 ), and placebo (PLA), administered via a double-dummy procedure (nine sessions per participant: 3 conditions &#xd7; 3 times of day) at 08:00, 12:00, and 18:00. Participants completed squat jump (SJ), countermovement jump (CMJ), block jump, attack jump, 10 &#xd7; 10 m t -test, spike accuracy, and serve accuracy assessments. Data were analyzed using two-way repeated-measures ANOVA. Significant main effects of condition and time of day were observed for all outcomes. Significant condition &#xd7; time-of-day interactions were found for SJ, CMJ, attack jump, and change-of-direction speed, indicating that caffeine-related ergogenic effects were most evident in the morning and at midday, whereas these benefits were attenuated in the evening when baseline performance was highest. At 08:00 and 12:00, both CAFcap and CAFrinse improved jump performance and agility compared with PLA, with capsule ingestion showing a small-to-moderate advantage over mouth rinsing for selected lower-limb power outcomes at midday (mean difference range: 0.51-0.57 cm; dz = 0.57-0.65). For block jump, spike accuracy, and serve accuracy, both caffeine conditions improved performance relative to placebo, while a progressive improvement across the day was observed under all conditions, including placebo, confirming a diurnal rhythm effect independent of supplementation. Overall, the data indicate that caffeine partially reduced the amplitude of diurnal variation in several physical performance measures. Both caffeine capsule ingestion and caffeine mouth rinsing enhanced physical and volleyball-specific performance in trained adolescent male volleyball players. The ergogenic effects were more pronounced earlier in the day, suggesting that caffeine may be particularly useful for attenuating morning and midday performance decrements, while mouth rinsing represents a practical non-ingestive alternative with meaningful efficacy.

Effects of Caffeine Ingestion on Morning Cognitive and Muscle Strength Measures in Males: A Standardized Approach [PMID: 41901129 · 2026]
Agulhari JPS, Chester N, Giacomoni M, Gibbons KC, Hajdukiewicz D, O'Brien HL, O'Brien TD, Jensen J, Lucas B, Moss SL, Pullinger SA, Edwards BJ · Nutrients (2026)

Background/Objectives : We investigated whether ingestion of caffeine (~1 h before) was beneficial to subsequent morning (07:30 h), mood, strength and cognitive measures. Methods : Fourteen recreationally active males were recruited and completed six sessions: (i) one repetition maximum (1RM) for bench press and back squat; (ii) two familiarization sessions of strength measures; (iv) three experimental conditions administered in a double-blinded, randomized counterbalanced design order, either caffeine (Caffeine [CAFF], 300 mg or 2.8-4.3 mg/kg body weight), placebo (Placebo [PLAC]) ingested at 06:30 h, or no-pill control (No Pill [NoPill]). For each experimental session, on arrival at the laboratory, rectal and skin temperature were measured as well as a battery of cognitive performance through a battery of tests (trail-making test, Rey's auditory verbal learning test, and Stroop word-colour interference test). Thereafter, maximum voluntary contraction on an isometric chair (MVC) without and with stimulation was conducted, and three repetitions were performed at 40, 60 and 80% of 1RM for bench press and back squat. Average power (AP), average velocity (AV), peak velocity (PV), mean propulsive velocity (MPV), average acceleration (RDV), displacement (D) and time-to-peak velocity (tPV) were recorded using MuscleLab linear encoders. Rating of perceived exertion and effort was asked after each set (RPE). The data was analysed using a general linear model with repeated measures. Results : MVC peak-force values with and without stimulation showed a significant increase in the CAFF condition compared to values for NoPill and with stimulation PLAC conditions (stim: &#x394;9.0 and 8.7%; no stim: 8.3%; p &lt; 0.05; &#x3b7; 2 p = 0.33 and 0.42). Greater muscle % activation was achieved for the CAFF than the other conditions (~6%, p &#x2264; 0.042; &#x3b7; 2 p = 0.33). In the non-stimulated MVC, RPE was perceived as easier (4.8%, p = 0.04). AV and MPV values were higher in both bench press (&#x394;3.3 and 4.6%) and back squat (&#x394;7.7 and 9.2%) in CAFF than the PLAC condition ( p = 0.031; &#x3b7; 2 p = 0.24 and 0.23 and 0.24 and 0.32). CAFF improved auditory total recall compared to NoPill (9.5%, p = 0.040; &#x3b7; 2 p = 0.22). Conclusions : Early morning ingestion of caffeine improved MVC to levels observed by others in the evening, as well as some aspects of bench press, back squat and recall performance. Caffeine ingestion had no effect on core temperature, mood, tiredness, alertness or other measures of cognitive performance.

High-Intensity Intermittent Exercise and Mouth Rinsing: A Systematic Review and Meta-Analysis [PMID: 41791366 · 2026]
Suen MW, Tsang JH, Wong PS, O'Reilly J, Poon ET · Int J Sport Nutr Exerc Metab (2026)

Carbohydrate (CHO), caffeine (CAF), and menthol (MEN) mouth rinses are emerging ergogenic aids that may enhance sports performance without the gastrointestinal risks of ingestion. However, there is limited evidence specifically regarding their effects on high-intensity intermittent exercise (HIIE) performance. This systematic review and meta-analysis aimed to evaluate the effect of mouth rinsing on HIIE performance, specifically focusing on solutions containing CHO, CAF, and/or MEN. A comprehensive literature search was conducted using seven databases through June 2025, following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Twenty randomized crossover studies were included. Overall, our meta-analysis revealed no significant improvement in overall HIIE performance following CHO mouth rinse (standardized mean difference = 0.18; 95% confidence interval [-0.10, 0.46]; p = .21), CAF mouth rinse (standardized mean difference = 0.37; 95% confidence interval [-0.02, 0.75]; p = .06), and CHO + CAF combined mouth rinse (standardized mean difference = -0.19; 95% confidence interval [-0.68, 0.30]; p = .44). Subgroup analysis based on HIIE performance outcomes, including power output, total distance covered, and sprint time, also showed no significant differences for any mouth rinse (p &gt; .05). MEN mouth rinse reported no performance benefits in hot environments, despite an improved cooling sensation. While some individual studies suggested improvements-particularly with low glycogen availability or frequent rinsing-the overall evidence does not support mouth rinsing as an ergogenic strategy for HIIE. Further well-controlled research is needed to define optimal rinse type, timing, frequency, and dietary context for HIIE applications.

Revisiting the evidence on caffeine mouth rinse: effects on exercise and cognitive performance: a meta-analytic review [PMID: 41774525 · 2026]
Deng H, Fan X, Song T, Bin Mohd Nasiruddin NJ, Ahmad Fuaad AA, Bin Naharudin MN · J Int Soc Sports Nutr (2026)

Caffeine mouth rinsing (Caff-MR) may activate oropharyngeal receptors and rapidly engage central networks for motivation, attention, and pacing without systemic absorption. The only prior meta-analysis found no stable ergogenic effect, yet the evidence base has continued to expand and remains heterogeneous. Six electronic databases were searched up to 2 October 2025 for Caff-MR studies on exercise and cognitive outcomes. Study quality was assessed using modified PEDro and RoB-2. Three-level meta-analyses synthesized both outcomes. Prespecified moderators were sex, training status, habitual caffeine use, feeding state, exercise or cognitive type, rinse duration, and total oral exposure. Sensitivity analyses addressed assumed within-subject correlations, outliers, and influential cases. Thirty-one studies (k&#x2009;=&#x2009;167 effects) met inclusion. Caff-MR was associated with trivial-to-small improvements in exercise performance (k&#x2009;=&#x2009;114; g&#x2009;=&#x2009;0.12, p &#x2009;=&#x2009;0.01). Benefits were most consistent for aerobic endurance and in the fed state; ~5-s rinses outperformed longer durations. Primary dose-response suggested a U-shape (32-133 mg window), but this pattern was not robust to outlier removal; under 5-s conditions, higher total exposure related negatively to performance. Cognitive effects were inconsistent overall (k&#x2009;=&#x2009;53; g&#x2009;=&#x2009;0.23, p &#x2009;=&#x2009;0.07), yet after outlier removal the overall and speed-based effects reached significance, whereas accuracy remained variable. Risk of bias was predominantly "some concerns"; GRADE certainty was moderate (exercise) and very low/low (cognition). Caff-MR is a practical, ingestion-free strategy yielding small, context-dependent benefits, optimized by brief (~5 s) rinses and moderate exposure, particularly for aerobic endurance. Standardized, well-powered trials are needed to refine dosing, timing, and cognitive applications. Caff-MR yields trivial-to-small exercise benefits, most reliably in aerobic endurance and the fed state . Brief (~5 s) rinses perform better than longer durations; escalating exposure does not improve outcomes.Primary U-shaped dose&#x2013;response was not robust; within 5-s rinses, higher exposure may negatively relate to exercise performance. Cognitive effects are task-dependent ; processing speed shows greater sensitivity than accuracy after outlier control.

Clinical Effectiveness of a Novel Caffeine Nano-Cream for Cellulite Reduction: A Randomised Double-Blind Trial [PMID: 41754894 · 2026]
Ponto T, Nastiti CMRR, Luna G, Leite-Silva VR, Moore BR, Wright A, Benson HAE · Pharmaceutics (2026)

Background : Caffeine (CAF), whether extracted from plants or synthesised as a chemical compound, is considered the safest among other xanthine alkaloids. Novel nano-cream formulations have been successfully developed and evaluated to increase the potential of caffeine as a skin cosmeceutical, targeting the minimisation of cellulite appearance. Methods : Nano-cream formulations were prepared through a process of hot-temperature emulsification, in a variety of homogeniser combinations. Results : When chemical penetration enhancers (CPEs) (lanolin, transcutol, and propylene glycol), either alone or in combination, were incorporated into the nano-cream formulations, the permeation of CAF through skin increased. All nano-cream formulations achieved sustained delivery of CAF into and through the skin over 8 h (IVPT). Quantification of CAF from skin tissues was achieved using high-performance liquid chromatography (HPLC). The nano-cream formulation containing lanolin (LAN) showed the highest CAF permeation (8.829 &#xb1; 1.472 &#xb5;g/cm 2 /h) through the skin compared to CAF in an aqueous solution (2.533 &#xb1; 0.480 &#xb5;g/cm 2 /h) and a commercial CAF cellulite product with the same CAF concentration (2.827 &#xb1; 0.555 &#xb5;g/cm 2 /h). Therefore, 2% CAF nano-cream formulation containing LAN was chosen for clinical testing. A double-blind, randomised, placebo-controlled paired trial was conducted, in which each volunteer applied active and placebo creams to the upper thighs twice daily for 12 weeks. The effect of the cream on skin appearance was monitored over 12 weeks. The primary outcome measures were reduced cellulite scores from 3.96 (95% CI: 3.16-4.76) to 2.50 (95% CI: 1.70-3.30) (active) compared with placebo from 3.88 (95% CI: 3.08-4.67) to 2.83 (95% CI: 2.03-3.63). The effect sizes (E.S.) indicated a moderate effect for the active CAF nano-cream formulation (E.S. = 0.475), while the placebo (E.S. = 0.286) had a small effect. Conclusion : We concluded that our optimised 2% CAF nano-cream formulation containing LAN offered an effective formulation strategy for enhancing skin penetration in the IVPT study. The LAN nano-cream formulation demonstrated efficacy and tolerability, both objectively and subjectively, in a human clinical trial.

Comparing Acute Effects of Caffeine Delivery Forms on Cross-Training Performance: A Randomized Placebo-Controlled Crossover Trial [PMID: 41754174 · 2026]
Vargas-Molina S, Bonilla DA, Garc&#xed;a-Sillero M, Iglesias-Placed S, Murri M, Mart&#xed;n-Rivera F, Ben&#xed;tez-Porres J · Nutrients (2026)

Background/Objectives : The aim of this study was to compare the different forms of caffeine (CAF) administration in CrossFit &#xae; participants. The countermovement jump (CMJ), the rate of perceived exertion (RPE), the total number of repetitions, and the maximum (HR max ) and mean heart rate (HR mean ) were evaluated. Methods : Fourteen males with more than six months of continuous CrossFit &#xae; training (30.9 [5.62] years, 179 [1.33] cm, 78 [5.75] kg, 24.3 [1.33] kg&#xb7;m -2 ) participated in this randomized, placebo-controlled, crossover study. Participants were randomized in a repeated measures design using caffeine capsule (CC), caffeine chewing gum (CCG), and caffeine mouth rinse (CMR) protocols, along with a placebo group (PG). Participants were unaware of whether any of the delivery methods contained caffeine. A 7-day washout period before each crossover was used. To ensure ecological validity, we replicated the real-world practice of CAF ingestion 30 min prior to training, mirroring typical athlete pre-workout routines. The participants of CrossFit &#xae; performed the 'Cindy' protocol, and the CMJ as a primary outcome was measured pre- and post-intervention, while the RPE, HR, and the number of repetitions were tracked at the end of the workout for comparisons. Results : No significant differences were found between CAF forms in internal load measures (RPE, HR max , HR mean ) or the number of repetitions. While no changes were observed with other CAF forms, CMR significantly improved the CMJ performance compared to the baseline (&#x394;: +3.5; Cohen's d unb : 0.51], which exceeded the estimated SWC by approximately three-fold. However, the inferential analysis revealed no significant main effects of the caffeine administration method on any measured outcomes. Conclusions : While CAF delivery forms did not improve internal load measures or performance parameters, such as the RPE, HR, or the total number of repetitions, the caffeine mouth rinse (CMR) showed a potentially meaningful improvement in CMJ performance after CrossFit &#xae; training in participants with a certain level of experience.

Green tea-derived exosome-like nanoparticles attenuate oxidative stress-induced skin senescence via modulation of p38 MAPK signaling [PMID: 42131805 · 2026]
Choi W, Cho JH, Park SH, et al. · Front Pharmacol (2026)

Plant-derived exosome-like nanoparticles (PDENs) have emerged as bioactive nanostructures capable of transferring molecular cargos across species; however, their mechanistic roles in mammalian stress-responsive signaling remain incompletely defined. In this study, we investigated the effects of green tea ( Camellia sinensis (L.) Kuntze [Theaceae])-derived exosome-like nanoparticles (GtDENs) on oxidative stress-induced cellular dysfunction in human keratinocytes. To do this, we employed MTT assay, immunoblotting analysis, real-time PCR method, SA-beta-gal assay, flowcytometry, and molecular docking model. GtDENs exhibited no detectable cytotoxicity and significantly attenuated hydrogen peroxide- and UVB-induced reactive oxygen species (ROS) accumulation and cell death. GtDENs suppressed oxidative stress-associated cellular senescence and apoptotic gene expression, including MMP3, p21, and caspases. Mechanistically, GtDENs preferentially reduced phosphorylation of p38 MAPK and downstream c-Fos activation under oxidative stress conditions, while ERK and JNK signaling remained largely unaffected. Functional analyses, including p38 overexpression and pharmacological inhibition experiments, support the involvement of p38 MAPK signaling in mediating GtDEN activity. Phytochemical profiling identified caffeine as the predominant small-molecule component within GtDENs. Molecular docking and cellular thermal shift assays suggest potential interaction between caffeine and p38 MAPK, although direct biochemical binding validation was not performed. Exploratory small RNA profiling further indicated the presence of regulatory RNA species associated with stress-responsive pathways. Collectively, these findings indicate that GtDENs modulate oxidative stress-responsive signaling, with p38 MAPK emerging as a key signaling axis involved in this response.

Vasorelaxing Effect of Hydrolyzed Collagen from Salmon Skin in the Thoracic Aorta and Underlying Mechanisms [PMID: 42123662 · 2026]
Mungmuang P, Onsa-Ard A, Tocharus J, et al. · Int J Mol Sci (2026)

Hydrolyzed collagen (HC) derived from salmon skin is a promising source of bioactive peptides. In this study, the vasorelaxant effects and potential mechanisms of action of HC on isolated rat thoracic aorta rings were investigated using the organ bath technique. The vasorelaxant properties of HC were evaluated using aortic rings from Wistar rats pre-contracted with phenylephrine (PE) or potassium chloride (KCl). HC induced significant vasorelaxation in both endothelium-intact and endothelium-denuded rings, indicating that its mechanism of action was independent of the endothelium and involved direct effects on vascular smooth muscle cells. The vasorelaxant effect of HC was reduced when pre-contraction was induced by tetraethylammonium chloride (TEA). However, the vasodilatory effects of HC were not significantly inhibited by all K + channel blockers, including glibenclamide, barium chloride (BaCl 2 ), or 4-aminopyridine (4-AP). Additionally, pre-incubation with prazosin, an &#x3b1;-adrenoceptor blocker, significantly reduced the vasorelaxation induced by HC, whereas propranolol, a &#x3b2;-adrenoceptor blocker, had no effect. In addition, HC inhibited CaCl 2 -induced contractions induced by both PE and caffeine in a Ca 2+ -free solution. Therefore, HC exhibited the vasorelaxant effects through an endothelium-independent mechanism. The vasodilatory effects of HC were associated with the activation of K Ca channels, suppression of PE-induced contraction via &#x3b1; 1 -adrenergic receptor pathways, and inhibition of CaCl 2 -induced contractions by modulating intracellular Ca 2+ release and extracellular Ca 2+ influx in vascular cells.

Efficient aqueous solubilization of methylxanthines via complexation with natural polyphenolate salts [PMID: 42040972 · 2026]
Hamonou E, Antonczak S, Shenderovich IG, et al. · RSC Adv (2026)

Caffeine, theophylline and theobromine are methylxanthines, a class of alkaloids present in coffee, tea and cocoa and therefore widely consumed all around the world. They exhibit several biological properties making them useful ingredients in cosmetics, as food additives or in pharmaceutical formulations. However, their solubility in water is limited. Extraction and purification often require the use of petrochemical volatile organic solvents. In the present paper, the solubility in water of caffeine, theophylline and theobromine in the presence of various natural solubilizing agents is reported. Niacinamide, as well as sodium or cholinium levulinate, salicylate, ferulate or caffeate were used to enhance the solubility of these methylxanthines in water. For example, solubility of theobromine was found to increase by a factor of 300 in aqueous solutions of ferulate salt. Solubilization mechanisms were investigated experimentally using 1 H NMR and 2D ROESY-NMR and theoretically using molecular dynamics simulations. Both studies point towards the presence of &#x3c0;-stacking-type interactions between methylxanthines and solubilizing compounds. Benzene-based moieties exhibit stronger interactions and &#x3c0;-stacking with caffeine than pyridine-based moieties, such as nicotinic acid and niacinamide. These compounds can therefore be considered as complexing agents for methylxanthines rather than hydrotropes. Importantly, the linear dependence of solubility on solubilizing agent concentration indicates that these complexes maintain their solubilized state upon dilution, thereby enabling complete miscibility in water without precipitation.

Spatial occurrence and distribution of micropollutants (pharmaceuticals and personal care products) in the eThekwini catchment, South Africa [PMID: 41985610 · 2026]
Lawrence TI, Sims N, Kasprzyk-Hordern B, et al. · Environ Pollut (2026)

This study presents, for the first time, the spatial and short-term temporal occurrence of forty-two multiclass pharmaceuticals, their metabolites, and personal care products in wastewater across a catchment area with and without rivers connected to wastewater treatment plants (WWTPs) in the eThekwini Metropolitan Municipality of South Africa. Four major WWTPs were studied, each with different wastewater treatment technologies and their receiving water bodies, over a week. This study compared the efficiency of the treatment plants and found that the removal efficiency depends on the treatment process employed. Wastewater treatment plants that employed activated sludge consistently achieve higher removal efficiencies for pharmaceuticals and personal care products (PPCPs) than plants that rely solely on screening and sedimentation. Most detected PPCPs increased downstream, indicating contributions from WWTP effluent; however, for some compounds, lower concentrations in the effluent relative to upstream concentrations led to dilution after mixing, demonstrating the combined influence of effluent inputs and hydrological mixing on river water quality. There is also concern about synergistic effects from the combination of these PPCPs, which may be detrimental despite their presence at trace levels. Among the PPCPs monitored, 26 were detected in the influent and effluent, with the most detected PPCPs in both being benzophenone-3, metformin, gliclazide, atenolol, carbamazepine, carbamazepine-10,11-epoxide, 10,11-dihydro-10-hydroxycarbamazepine, nicotine, caffeine, 1,7-dimethylxanthine, N-desmethyltramadol, and O-desmethyltramadol. The weekday-weekend concentrations of some PPCPs (citalopram, 1,7-dimethylxanthine, nicotine, metformin, atenolol, cimetidine, benzophenone-3, gliclazide, quetiapine, and 10,11-dihydro-10-hydroxycarbamazepine) were significantly different across the various plants, indicating variation in the consumption habits of the people these plants serve. The highest concentrations in the influents and effluents were observed for 1,7-dimethylxanthine (a metabolite of caffeine), with mean concentrations of 723&#xa0;668.4&#xa0;&#xb1;&#xa0;180&#xa0;002.5&#xa0;ng&#xa0;L -1 and 409&#xa0;405.7&#xa0;&#xb1;&#xa0;173&#xa0;761.3&#xa0;ng&#xa0;L -1 , respectively. Except for acetaminophen, desvenlafaxine, carbamazepine-10,11-epoxide, nicotine, caffeine, and 1,7-dimethylxanthine in one or two treatment plants, the majority of the PPCPs in the effluent showed an insignificant to medium aquatic risk (this level of risk is similar for the studied surface water), based on an ecotoxicological risk assessment. Given that these PPCPs are present as complex mixtures with diverse physicochemical properties and varying capacities to influence a range of molecular and cellular processes in organisms, a better understanding of their ecological risk is needed to promote environmental health.

Ecotoxicological assessment of Zantedeschia aethiopica (L.) and Eisenia foetida Savigny exposure to pharmaceutical and personal care products, and hazelnut shell [PMID: 41965162 · 2026]
Costa-Conceicao K, Villamar-Ayala CA, Ortiz-Calderón C, et al. · Sci Total Environ (2026)

Porous media are the most frequent fate of pharmaceutical and personal care products (PPCPs) during wastewater treatment using nature-based solutions (NBS, e.g. biofiltration). Caffeine, ibuprofen, losartan, and triclosan are pseudo persistent contaminants, generating chronic toxicity, and hydrolysis of organic support as porous media could cause effects on biotic components (plants and earthworms) of biofilters. Therefore, the aim of this study was to evaluate chronic effect (LOEC: lowest observed effect concentration or NOEC: Non-Observed Effect Concentration and biomarkers) of hazelnut shells and PPCPs on plants (Zantedeschia aethiopica (L.)) and annelids (Eisenia foetida Savigny). Annelids (survival, number of cocoons, and weight) and plants (apical growth, diameter basal, chlorophyll a and b, biomarkers) were exposed to different concentrations (Control (0), 12.5, 25, 50 and 100%) of PPCPs (triclosan, ibuprofen, losartan, caffeine) and hazelnut shells. Results showed reduced plant growth (high apical/basal diameter) exposure to hazelnut shell (LOEC&#xa0;=&#xa0;25%). Meanwhile, earthworms reported weight loss to hazelnut shell (LOEC&#xa0;=&#xa0;12.5%) exposure. Non-monotonic (hormetic type) dose-response relationships were observed in both plants and earthworms. The lowest concentration inducing the most pronounced sublethal effects on plants (basal diameter&#xa0;=&#xa0;-10.72&#xa0;mm) and earthworms (weight loss&#xa0;=&#xa0;0.35&#xa0;g) was at triclosan concentrations of 12.5%. Plants exhibited oxidative stress under PPCP exposure (12.5-25%), due to cellular damage induced by hydrolyzed compounds, which triggered antioxidant defense mechanisms and disrupted metabolic homeostasis. Organic residues can serve as promising filter porous in biofiltration. However, chronic exposure to PPCPs may induce molecular-level effects (e.g., redox disruption, enzymatic modulation), highlighting the need for careful material selection and long-term ecotoxicological assessment.

Occurrence and ecological risk of pharmaceuticals and personal care products in Djibouti's coastal waters [PMID: 41785591 · 2026]
Adaneh AE, Ahmed MM, Wong-Wah-Chung P, et al. · Mar Pollut Bull (2026)

Pharmaceuticals and personal care products (PPCPs) are recognized as emerging organic contaminants in marine environments and have gained worldwide attention. The aim of this study is to investigate for the first time, the occurrence, and potential ecological risks of PPCPs in the Djibouti's coastal waters. 25 PPCPs from 11 therapeutic groups of human and veterinary medicine were sought in water samples collected from 7 stations in the Gulf of Tadjourah and three estimation approaches (mRQ MEC/PNEC , mRQ STU , MCR) were explored to assess ecological risks to aquatic life. 16 out of the 25 PPCPs belonging to 5 human therapeutic classes (analgesic-anti-inflammatory, antibiotic, stimulant, topical analgesic, and antiepileptic) were detected in the Djiboutian coastal water samples, with concentrations ranging from 2.29 to 684.75&#xa0;ng/L. To our knowledge, levofloxacin and capsaicin presence were confirmed for the first time in Djibouti coastal waters, indicating an additional risk to aquatic biota. Most offshore sites (M3, M4 and M5) exceeded the risk threshold based on sensitive mRQ MEC/PNEC approach with RQ values higher than 145, 657 and 155, respectively. This result was mainly attributed to the detection of ibuprofen, carbamazepine, and caffeine at high levels. Station M4, the most polluted, is characterized by the direct discharge of untreated urban and hospital wastewater onto the coastline, notably from the unique Djiboutian tuberculosis treatment center. This work would contribute to future research on the Gulf Aden and East Africa coast and help to implement environmental policies related to PPCPs on the East Africa coast.

자주 묻는 질문 (AEO 스니펫 최적화 FAQ)

Q1. 카페인 (CAFFEINE)의 국가별 공식 전성분 표기명은 어떻게 다른가요?
한국 식약처 표준명은 '카페인', 미국 PCPC 및 유럽 CosIng INCI 표기는 'CAFFEINE', 중국 NMPA IECIC 표준명은 '咖啡因', 일본 화장품 표시명칭은 'カフェイン'입니다.
Q2. 카페인의 글로벌 6대 권역 법정 배합 한도(Layer 1)는 무엇인가요?
한국(KR: none), 유럽(EU: none), 미국(US: none), 중국(CN: allowed), 일본(JP: restricted), 아세안(ASEAN: none) 고시 기준을 준수하여 처방해야 합니다.
Q3. 제형 설계 시 카페인의 통상 배합 농도(Layer 3)와 적정 pH는 얼마인가요?
대표 제형군(emulsion_cream) 기준 통상 0.1~1%(권장 중앙값 1%) 범위로 투입하며, 적정 pH는 4~8입니다.
Q4. 카페인 배합 시 주의해야 할 상용성 금기(Incompatibilities)와 시너지 성분은 무엇인가요?
주요 권장 시너지 조합은 GLYCERIN, CAPRYLIC/CAPRIC TRIGLYCERIDE, TOCOPHEROL이며, 배합 주의사항은 처방 내 극단적 pH 조건 및 고농도 전해질과의 상용성 사전 확인 권장입니다.