The Science of Acne: Root Causes, the Four-Pathway Model, and Why Treatments Work

Acne vulgaris is one of the most prevalent skin conditions globally — affecting up to 85% of adolescents and a significant proportion of adults — and one of the most incompletely understood by the people who have it. The narrative that acne is caused by dirty skin, poor diet, or insufficient cleansing is both pervasive and wrong. It creates a cycle of shame-driven over-cleansing and barrier destruction that consistently makes acne worse. The actual pathology of acne involves four converging biological processes that operate at the follicular level, and understanding them explains not just why acne happens but why specific treatments work and others don't — and why some widely used approaches actively aggravate the condition they are meant to treat.

Pathway 1: Excess Sebum Production

Sebum is produced by sebaceous glands attached to hair follicles throughout the face, scalp, chest, and back. Sebum production is primarily regulated by androgens — particularly DHT (dihydrotestosterone) — which bind to androgen receptors in sebocytes (sebum-producing cells) and stimulate lipid synthesis. This is why acne predominantly develops during puberty when androgen levels surge, why hormonal acne in adult women often tracks with the menstrual cycle, and why anti-androgen therapies (spironolactone, oral contraceptives containing anti-androgenic progestins) are effective for hormonal acne patterns.

Sebum composition also matters. Acne-prone skin produces sebum with elevated levels of squalene and reduced levels of linoleic acid relative to sebum in non-acne-prone skin. Linoleic acid is an essential fatty acid that normally helps maintain the integrity of the follicular wall — its deficiency is associated with microcomedone formation. When squalene is oxidised by UV and reactive oxygen species, it produces highly comedogenic squalene peroxides that directly trigger follicular inflammation. This is one mechanism by which UV exposure can worsen acne — not through the widely believed "drying" benefit.

Pathway 2: Abnormal Follicular Keratinisation

Under normal conditions, keratinocytes lining the follicular wall shed continuously, mixing with sebum and being expelled at the surface. In acne-prone follicles, this desquamation process is dysregulated — keratinocytes overproduce, adhere abnormally to each other rather than shedding individually, and accumulate within the follicular canal. Combined with excess sebum, this builds into a microcomedone — a microscopic plug that is the precursor to every visible acne lesion.

The microcomedone is not yet a visible blackhead, whitehead, or pimple. It is an invisible accumulation of keratin and sebum inside the follicle. Over weeks, it either expands to become a closed comedo (whitehead), oxidises at the opening to become an open comedo (blackhead), or becomes colonised by bacteria and inflamed to produce papules and pustules. This follicular plugging stage is the target of comedolytic treatments — retinoids and salicylic acid both normalise keratinisation in the follicular wall, preventing microcomedone formation rather than just treating visible lesions.

Pathway 3: Cutibacterium acnes Colonisation

Cutibacterium acnes (formerly Propionibacterium acnes) is a gram-positive anaerobic bacterium that is a normal component of the skin microbiome, present on all skin. It becomes pathogenic in the acne context not because it is foreign but because of the conditions created by pathways 1 and 2: the microcomedone's anaerobic, lipid-rich environment is ideal for C. acnes proliferation. As C. acnes multiplies, it metabolises sebum triglycerides into free fatty acids using its lipase enzymes — these free fatty acids are comedogenic and pro-inflammatory, further driving the cycle.

Modern understanding of acne microbiology has shifted from "C. acnes causes acne" to recognising that specific C. acnes phylotypes (genetic strains) are more associated with acne-prone skin than others, and that the balance of C. acnes strains — rather than total C. acnes abundance — may be more relevant. The skin microbiome perspective explains why long-term antibiotic use for acne has significant limitations: it disrupts the broader skin microbiome and selects for resistant strains without addressing the sebum and keratinisation drivers that created the hospitable environment in the first place.

Pathway 4: Inflammation

The immune response to C. acnes components (particularly its cell wall proteins and lipase products) is what converts a comedone into an inflamed papule or pustule. Toll-like receptors on keratinocytes and sebocytes recognise C. acnes components, triggering the release of pro-inflammatory cytokines — particularly IL-1α, IL-8, and TNF-α. This cytokine cascade recruits neutrophils into the follicle, producing the pus characteristic of a pustule and the redness and swelling of a papule.

Critically, research by Dréno and others has demonstrated that inflammation is not simply a consequence of C. acnes infection — IL-1α is produced by keratinocytes in the follicular wall even before visible comedone formation, suggesting that inflammatory processes initiate early in the microcomedone stage. This explains why purely antibacterial approaches to acne treatment (targeting only C. acnes) are insufficient for many patients — the inflammatory pathway is partially independent of bacterial load.

Hormonal Acne: The Androgen Driver in Adults

Adult acne — particularly in women aged 25–45 — is predominantly hormonally driven, and understanding this changes which treatments are appropriate. The pattern is characteristic: deep, tender cysts or nodules concentrated on the lower face, jawline, and neck; breakouts that track with the menstrual cycle (typically worsening in the week before menstruation when oestrogen falls and relative androgen dominance increases); and poor response to the topical acne treatments that work well for teenage comedonal acne.

The mechanism is the androgen pathway described in Pathway 1: DHT binds to androgen receptors in sebocytes and triggers sebum overproduction and inflammatory signalling. In adult women, the relevant hormonal drivers include: the normal luteal phase androgen rise before menstruation, PCOS (polycystic ovary syndrome — associated with chronically elevated androgens), and the relative androgen excess that can follow stopping combined oral contraceptives that were previously providing anti-androgenic suppression. Elevated IGF-1 (insulin-like growth factor 1), driven by high glycaemic index diet and dairy consumption in some individuals, also stimulates androgen receptor activity in sebocytes — this is the biological link between diet and acne in people with IGF-1 sensitivity.

Treatment implications: topical retinoids and antibiotics address the downstream pathways (keratinisation, C. acnes) but do not reduce androgen signalling. For hormonally driven adult acne, the most effective interventions address the androgen driver directly — spironolactone (an anti-androgen, reduces DHT activity at the receptor level), combined oral contraceptives containing anti-androgenic progestins (drospirenone, cyproterone acetate in markets where available), or isotretinoin for severe cases. These are prescription medications requiring medical consultation — but understanding that the root cause is hormonal explains why endless topical approaches produce limited results for this specific pattern.

Diet, Lifestyle, and the Acne Evidence

The relationship between diet and acne is more evidence-supported than the dermatological mainstream acknowledged for decades — and more nuanced than the popular narrative of "chocolate causes breakouts." Two dietary factors have consistent, mechanistically coherent evidence: high glycaemic index (GI) foods and dairy.

High-GI foods (white bread, refined sugar, processed carbohydrates) raise blood glucose and insulin rapidly, which stimulates hepatic and peripheral IGF-1 production. IGF-1 directly stimulates androgen receptor expression in sebocytes, increases sebum production, and promotes the abnormal follicular keratinisation of Pathway 2. A 2007 randomised controlled trial by Smith et al. found that a low-GI diet over 12 weeks produced significant reductions in acne lesion count compared to a high-GI diet — one of the most rigorous dietary acne studies conducted. Not everyone's acne is equally sensitive to glycaemic index, but for people whose acne worsens noticeably with high-sugar periods, the mechanism is real.

Dairy — particularly skimmed milk — has been associated with acne in multiple epidemiological studies, with the association being stronger for skimmed than for whole milk (counterintuitively). The proposed mechanisms include bovine IGF-1 in milk, whey protein stimulating endogenous IGF-1 production, and hormones in dairy products influencing sebaceous gland activity. The evidence is observational rather than trial-based, but the biological plausibility is sufficient that a dairy elimination trial is a reasonable diagnostic step for acne that does not respond well to standard treatments.

Cortisol — the primary stress hormone — stimulates sebum production through CRH (corticotropin-releasing hormone) receptors in sebocytes and mast cells in the dermis. This is why skin reliably worsens during high-stress periods: cortisol both increases sebum output and triggers mast cell degranulation, producing an inflammatory state that turns existing microcomedones into inflamed lesions faster. Sleep deprivation, which elevates cortisol and impairs barrier repair during the night, compounds this. See our guide on whether stress affects skin for the full cortisol-skin relationship.

Why Treatments Work: Matching Mechanism to Pathway

What Does Not Cause Acne

Surface hygiene does not cause or prevent acne — the microcomedone forms inside the follicle, driven by sebum and keratinisation. Over-cleansing strips barrier lipids, increases skin sensitivity, can worsen post-inflammatory marks, and does nothing to reduce sebum production or correct follicular keratinisation. Similarly, while high-glycaemic diet and dairy have been associated with acne in some epidemiological studies — through IGF-1 and insulin-mediated androgen stimulation — this is a contributing factor for some people, not a universal cause. Stress worsens acne through CRH (corticotropin-releasing hormone) stimulation of sebocytes, not through "toxins." And chocolate, long a popular acne villain, has limited supporting evidence independent of its sugar content.

For the practical acne-prone skincare routine built on these mechanisms, see our guides on acne and sensitive skin routines, benzoyl peroxide, and adapalene. Use the Skin Stacker Routine Builder to map a routine targeting the pathways most relevant to your acne pattern.