Acne: The Gut-Hormone-Insulin Triangle

The Skin Is Speaking

Dermatology treats acne as a local skin problem: excess sebum, clogged pores, bacterial overgrowth, inflammation. Apply a retinoid. Prescribe an antibiotic. If that fails, isotretinoin. If it is hormonal, birth control pills. The lesion is the target. The skin is the battlefield.

Functional medicine sees it differently. The skin is not the battlefield. The skin is the messenger. Acne is a systemic inflammatory condition with cutaneous expression. The real drivers — insulin dysregulation, hormonal imbalance, gut dysfunction, and dietary triggers — are operating beneath the surface. Until those are addressed, topical treatments manage symptoms while root causes persist.

Loren Cordain’s 2002 observation set the frame: acne is virtually absent in non-Westernized populations eating traditional diets. He studied the Kitavan Islanders of Papua New Guinea (1,200 people) and the Ache hunter-gatherers of Paraguay (115 people). Not a single case of acne in either group. Zero. This is not genetics — when these populations adopt Western diets, acne appears within a generation. Acne is a disease of civilization, and the primary civilizational variable is diet.

The Insulin-IGF-1-Androgen Axis

This is the master pathway. High-glycemic foods spike blood glucose, which spikes insulin. Insulin does three things relevant to acne:

First, insulin elevates insulin-like growth factor 1 (IGF-1). IGF-1 stimulates sebocyte proliferation — the sebaceous glands enlarge and produce more sebum. More sebum means more substrate for Cutibacterium acnes (formerly Propionibacterium acnes) to metabolize, producing inflammatory byproducts.

Second, insulin increases androgen bioavailability. It does this by suppressing sex hormone-binding globulin (SHBG) and by directly stimulating ovarian and adrenal androgen production. More free testosterone means more conversion to dihydrotestosterone (DHT) via 5-alpha reductase in the skin. DHT is the most potent stimulator of sebaceous gland activity.

Third, insulin and IGF-1 activate the mTORC1 pathway (mechanistic target of rapamycin complex 1), which drives cell proliferation, lipogenesis in sebocytes, and suppresses autophagy. Melnik (2012) has argued that acne is fundamentally an mTORC1-driven disease — the same pathway implicated in cancer, aging, and metabolic syndrome.

This is why acne and PCOS so frequently coexist. PCOS is characterized by insulin resistance and hyperandrogenism — the same two drivers of acne. Treating the insulin resistance addresses both conditions simultaneously.

Dairy and Acne

The evidence against dairy — particularly skim milk — is now substantial. Adebamowo’s analyses from the Nurses’ Health Study II (2005, 2006) and the Growing Up Today Study (2006) demonstrated a positive association between dairy intake and acne in both women and adolescent boys. The relationship was strongest for skim milk, weaker for whole milk, suggesting the mechanism is not fat-related.

Three mechanisms explain dairy’s acne-promoting effects:

1. Insulin and IGF-1: Cow’s milk is designed to promote rapid growth in calves. It contains bioactive insulin-like growth factors that survive digestion and enter human circulation. Dairy consumption raises serum IGF-1 levels.

2. Hormonal content: Dairy contains 5-alpha reduced steroids (DHT precursors), estrogens, and progesterone — even organic milk, because cows are milked during pregnancy when hormone levels are highest.

3. A1 beta-casein: The A1 variant of beta-casein (predominant in Holstein cows, which produce most commercial milk) generates beta-casomorphin-7 upon digestion, which promotes inflammation and has been linked to various inflammatory conditions.

Whey protein supplementation deserves specific mention — it is a concentrated insulin secretagogue and IGF-1 booster. Bodybuilders and athletes supplementing with whey protein frequently develop acne, even without prior history. Switching to plant-based protein (pea, hemp, rice) typically resolves it within 4-8 weeks.

The Gut-Skin Axis

Bowe and Logan (2011) revived and expanded the Stokes-Pillsbury gut-brain-skin theory from 1930, demonstrating that gut dysbiosis, intestinal permeability, and SIBO contribute to systemic inflammation that manifests as acne.

The mechanisms:

• SIBO: Small intestinal bacterial overgrowth is significantly more prevalent in acne patients (Parodi 2008). Bacterial overgrowth produces lipopolysaccharides (LPS) that enter circulation through a permeable gut lining, activating toll-like receptors and NF-kB inflammatory cascades. This systemic inflammation reaches the skin.
• Dysbiosis: Reduced microbial diversity, particularly low Lactobacillus and Bifidobacterium, correlates with acne severity. Gut microbes modulate systemic inflammation, insulin sensitivity, and hormone metabolism.
• Intestinal permeability: “Leaky gut” allows food antigens, bacterial products, and inflammatory mediators to enter circulation. The skin — as the body’s largest immune organ — becomes a secondary battleground.

Hormonal Acne in Women

Acne that concentrates along the jawline, chin, and lower cheeks in women is classically hormonal — driven by androgens. The pattern reflects the distribution of androgen-sensitive sebaceous glands.

Key hormonal drivers:

• Elevated testosterone and/or DHEA-S: Often seen in PCOS but can occur independently
• Elevated DHT: 5-alpha reductase converts testosterone to DHT in the skin; some women have genetically higher 5-alpha reductase activity
• Low SHBG: Allows more free testosterone to reach skin receptors
• Oral contraceptive withdrawal: Pills containing anti-androgenic progestins (drospirenone, cyproterone acetate) suppress androgens. Stopping them produces a rebound surge — acne often erupts 3-6 months after discontinuation
• Perimenopause: Declining estrogen with relatively preserved androgens shifts the ratio

Testing: free and total testosterone, DHEA-S, androstenedione, SHBG, fasting insulin, DHT (if available), DUTCH test for androgen metabolites (5-alpha vs 5-beta pathway preference).

Spironolactone is the pharmaceutical workhorse for hormonal acne — it blocks androgen receptors and inhibits 5-alpha reductase. Typical dosing: 50-100mg daily, can go to 200mg. Requires monitoring of potassium (potassium-sparing diuretic) and is contraindicated in pregnancy (anti-androgen effects on male fetus). Takes 3-6 months for full effect.

The Functional Acne Protocol

Dietary Foundation

Low glycemic: Smith’s 2007 randomized controlled trial — 43 young men randomized to low-glycemic or standard diet for 12 weeks. The low-glycemic group showed significant improvements in acne lesion count, weight, insulin sensitivity, and androgen levels. The dietary intervention outperformed most topical treatments in the study.

Eliminate dairy: Strict 60-day elimination. This is the single dietary intervention with the most consistent clinical results.

Anti-inflammatory framework: Omega-3-rich fish (wild salmon, sardines, mackerel), colorful vegetables (6-8 cups daily), turmeric, ginger, green tea, berries. Avoid sugar, refined carbohydrates, fried foods, processed seed oils.

Supplement Protocol

Supplement	Dose	Evidence	Notes
Zinc picolinate	30-50mg	Dreno 2001 — comparable to 100mg minocycline after 3 months	Take with food, supplement copper 1-2mg if >30mg zinc long-term
Probiotics (L. rhamnosus SP1)	3 billion CFU	Fabbrocini 2016 — improved acne after 12 weeks	Multi-strain also beneficial
Omega-3 (EPA focus)	2-3g EPA+DHA	Anti-inflammatory, sebum composition	EPA is the anti-inflammatory fraction
DIM (diindolylmethane)	200mg	Shifts estrogen metabolism, mild anti-androgen	Derived from cruciferous vegetables
Berberine	500mg 2x daily	Insulin sensitizer, comparable to metformin	Test liver enzymes; antimicrobial (supports gut)
NAC (N-acetylcysteine)	600mg 2x daily	Glutathione support, anti-inflammatory, anti-androgen	Also supports liver detox of hormones
Vitamin A (retinyl palmitate)	10,000 IU	Sebum regulation, skin cell turnover	Contraindicated in pregnancy; monitor liver if high-dose
Vitamin D3	Test and optimize to 50-70 ng/mL	Anti-inflammatory, immune modulation, antimicrobial peptides	Low vitamin D correlates with acne severity

Gut Protocol for Acne

• Test for SIBO (lactulose breath test) — treat if positive (herbal antimicrobials: berberine, oregano oil, neem — or rifaximin)
• Comprehensive stool analysis (GI-MAP) for dysbiosis, inflammation markers, pathogen screening
• L-glutamine 5g daily for intestinal barrier integrity
• Probiotics: L. rhamnosus, L. plantarum, B. lactis
• Prebiotic fiber (gradual increase): partially hydrolyzed guar gum, GOS, resistant starch
• Bone broth: collagen and glycine for gut lining repair
• Remove additional food triggers identified through elimination or testing

Topical Functional Approach

• Niacinamide (vitamin B3) 4-5%: Draelos 2006 — comparable to 1% clindamycin gel. Anti-inflammatory, sebum-reducing, improves skin barrier. Well-tolerated, no antibiotic resistance
• Tea tree oil 5%: Bassett 1990 — comparable to 5% benzoyl peroxide, slower onset but fewer side effects. Antimicrobial (C. acnes) without antibiotic resistance
• Azelaic acid 15-20%: Anti-inflammatory, antimicrobial, inhibits tyrosinase (fades post-inflammatory hyperpigmentation). Pregnancy-safe. Available over-the-counter at 10%
• Tretinoin (vitamin A derivative) 0.025-0.1%: Gold standard retinoid. Normalizes keratinocyte turnover, prevents comedone formation. Start low, increase gradually. Causes initial purging (4-6 weeks). Must use sunscreen. Prescription
• Zinc pyrithione: Antimicrobial, anti-inflammatory. Available in cleansers
• Green tea extract topical: EGCG reduces sebum and inflammation

Lifestyle Factors

• Sleep: Growth hormone released during deep sleep supports skin repair. Disrupted sleep increases cortisol → increases sebum → worsens acne
• Stress management: Cortisol stimulates sebaceous glands. Chronic stress measurably worsens acne (Chiu 2003 — exam stress study)
• Exercise: Improves insulin sensitivity, reduces androgens, supports detoxification through sweat. Shower immediately after — sweat + bacteria + friction = mechanica
• Don’t touch the face: Mechanical irritation + bacterial transfer. This includes phone screens pressed against cheeks
• Clean pillowcase: Change every 2-3 nights. Silk or satin reduces friction

The timeline for functional acne treatment is longer than isotretinoin — typically 3-6 months for significant improvement. But the results address the whole system. The skin clears because the body underneath has changed. Hormones rebalance. Insulin normalizes. The gut heals. Inflammation recedes. The messenger finally has nothing left to say.

If acne is the body’s way of telling you something is out of balance internally, what else might clear up when you actually listen?