This Is Why 99% of Skin Conditions Don't Heal — And What Dermatologists Won't Tell You

Episode Overview

• Dr. Mark Hyman (Co-founder of Function Health, Seed Clinical Board member, and daily user of podcast sponsor Timeline Nutrition's Mitopure) and board-certified dermatologist Dr. Mamina Turegano (Co-founder of the prescription skincare service DermClick) explore how internal systemic factors—gut health, insulin sensitivity, hormones, and mitochondrial function—drive chronic inflammatory skin conditions and skin aging.
• The discussion traces the root causes of acne, rosacea, psoriasis, and eczema to metabolic dysfunction and the gut-skin axis, illustrating why conventional immune-suppressing medications fail to address underlying drivers like SIBO, fungal overgrowth, and dietary triggers.
• The episode transitions from internal cellular mechanics—such as glycation, menopausal hormone shifts, and exercise-induced dermal thickening—to an evidence-based evaluation of topical skincare, separating proven ingredients (retinoids, vitamin C, mineral sunscreens) from overhyped or preliminary trends (beef tallow, exosomes, and salmon-sperm-derived PDRN).
• Listeners struggling with adult acne, autoimmune skin flares, or premature aging will learn how to pair an anti-inflammatory "inside-out" lifestyle with a targeted "outside-in" topical routine.

Key Concepts

• Insulin Resistance and Glycation in Skin Pathology: Dr. Hyman claims insulin resistance affects over 90% of Americans to some degree. At Function Health, even using Quest Diagnostics' abnormal cutoff of 18 or above for fasting insulin (whereas optimal is less than 5, and Dr. Hyman's own level at age 66 is 2 to 3), 65% of their over 500,000 members have high insulin and inflammation. In women, high insulin drives high testosterone, triggering acne. Furthermore, excess sugar binds to collagen fibers to form Advanced Glycation End-products (AGEs), making collagen brittle, prone to breaking down, and unable to remodel properly.
• The Gut-Skin Axis and Systemic Inflammation: Roughly one-third to one-half of all metabolites in the human bloodstream are produced by the gut microbiome rather than human cells. Research links rosacea and acne to higher rates of small intestinal bacterial overgrowth (SIBO), Helicobacter pylori, and gut fungal/yeast overgrowth. Low dietary fiber also slows bowel movements, causing a buildup of hormone metabolites that contribute to acne. While Dr. Turegano acknowledges controversy in conventional medicine regarding microbiome and heavy metal testing, Dr. Hyman notes that a lack of large double-blind randomized controlled trials for nutrition and lifestyle stems from a lack of financial incentives. At Cleveland Clinic, a study comparing functional medicine (elimination diet and gut repair without drugs) to standard rheumatology drug care for psoriatic and rheumatoid arthritis showed superior outcomes across the board for the functional medicine group.
• Dietary Drivers, Agricultural Shifts, and Stress: Over the last few decades, adult acne has risen alongside hypothyroidism, hair loss, and infertility—likely driven by agricultural hormones/feed in meat and dairy, glyphosate, endocrine-disrupting chemicals, and stress (which raises cortisol, increasing skin inflammation and making sebum sticky). For acne, the strongest dietary evidence implicates sugar and dairy, with skim milk showing a stronger association with breakouts than whole milk. In psoriasis and dermatitis, gluten sensitivity and anti-gluten antibodies can trigger flares even in non-celiac patients; though Dr. Turegano is not as adamant about strict gluten-free diets if patients test negative for antibodies, Dr. Hyman notes the innate immune system can react to gluten without measurable antibodies.
• Hormonal Decline and Skin Structure: Skin aging spans three structural layers, which Dr. Turegano compares to a bed: the epidermis (mattress cover), where cell turnover slows from every 2 weeks in babies to 4 weeks in adults and even slower in older adults, accompanied by unpredictable melanocytes (sunspots) and reduced sebaceous lipids; the dermis (springs), where collagen, elastin, and glycosaminoglycans like hyaluronic acid break down; and the subcutaneous fat and bone (bed frame), which resorb with age. Thyroid dysfunction impairs circulation and causes dry skin, brittle nails, and hair loss. During the first 5 years of menopause, a drastic drop in estrogen reduces fibroblast activation, collagen, hyaluronic acid, and skin thickness, while declining testosterone and androgens reduce sebum production. Dr. Turegano strongly supports Hormone Replacement Therapy (HRT) for women's skin health based on clinical observation, though she caveats that there are not many dedicated studies on HRT for skin and it is mostly observed as a side effect.
• Strength Training vs. Cardio for Dermal Thickness: In a small study of roughly 60 midlife women comparing aerobic exercise to strength training, both groups improved skin hydration and barrier function, but only the strength training group developed a thicker dermis. Dr. Turegano explains that strength training increases insulin sensitivity, lowers inflammation, and optimizes mitochondrial function so dermal fibroblasts can build more collagen, though she notes she would like to see more studies confirm this.
• Mitochondrial Mitophagy and Urolithin A: UV radiation—alongside alcohol (which stresses the liver and increases oxidative stress) and smoking—drives localized oxidative stress, DNA damage, and mitochondrial dysfunction. Urolithin A, a postbiotic produced by gut bacteria from polyphenols in pomegranates, walnuts, green tea, and cranberries, stimulates mitophagy (clearing damaged mitochondria). Because only about 40% of people have the gut microbiome required to convert dietary polyphenols into urolithin A, oral supplementation (specifically Mitopure, a podcast sponsor that Dr. Turegano notes is the only form with third-party validated, clinically studied dosing) can reduce C-reactive protein (CRP) and improve mitophagy, while topical urolithin A shows evidence for wrinkle reduction, hydration, and barrier repair.
• UV Radiation, Vitamin D, and the Melanoma Paradox: UV radiation accounts for roughly 80% of extrinsic skin aging. Non-melanoma skin cancers (basal cell and squamous cell carcinoma) stem from chronic, cumulative daily sun exposure. Conversely, melanoma is linked to intermittent, prolonged sun exposure and burns (most commonly on the back in men and legs in women), though some melanomas occur in non-sun-exposed areas like between the toes or the anal region. Paradoxically, studies show low vitamin D levels put people at a higher risk for melanoma. Regarding sun protection, the FDA classifies mineral sunscreens as GRASE (Generally Recognized As Safe and Effective), alongside a newer chemical filter called BEMT (Parsol Shield). Traditional chemical sunscreens absorb into the bloodstream, though Dr. Turegano notes we lack human data showing whether that absorption causes harm; she similarly takes the EWG Skin Deep database with a grain of salt because its toxicity data relies on impractically high doses in animal models.
• Evaluating Oral and Topical Skincare Ingredients: Oral collagen peptides do not travel to the skin intact, but act as signaling molecules to help the body build collagen; Dr. Turegano is "on team collagen" but caveats that much of the compelling data is industry-backed. Topically, she pushes back against Dr. Hyman's rule of only putting edible things on the skin, noting that edible lemon juice destroys the skin barrier, and dismisses beef tallow (and coconut oil) as comedogenic and ineffective for sun protection. While topical retinoids, vitamin C, niacinamide, ceramides, hyaluronic acid, and topical GHK-Cu (copper peptides) have solid evidence, Dr. Turegano notes injectable GHK-Cu lacks safety measures and evidence. Similarly, PDRN (derived from salmon sperm) has strong data as an injectable for wound healing and collagen remodeling, but less evidence topically beyond moisturizing. Finally, she describes topical and injectable exosomes and stem cells as "the wild wild west" due to lacking safety data, room-temperature instability (requiring freezing), and uncertainty over the best cellular source.

Quotes

• At 0:00:16 - "The participants who were strength training actually had a thicker dermis, you know, so dermis is where our collagen sits." - Dr. Turegano explaining a study of ~60 midlife women showing why resistance training outperforms cardio for structural skin aging.
• At 0:06:33 - "They're all suppressing your immune system, and it's just like, let's just shut up the immune system so that you can live in peace. But what I've noticed just practicing more and more is that it's not really getting to the root cause." - Dr. Turegano critiquing conventional dermatological treatments for chronic inflammatory skin conditions.
• At 0:09:33 - "We're seeing even at the reference range of Quest, 65% of members, of our over half a million members, have high insulin levels and have inflammation." - Dr. Hyman sharing diagnostic data from Function Health (using Quest's cutoff of 18 or above) to illustrate the prevalence of metabolic dysfunction driving skin issues.
• At 0:16:10 - "Stress can, you know, increase cortisol. So cortisol just sends a whole cascade of signals, including just like increased inflammation in our skin, increase—it makes our sebum more sticky, so like we get more acne from that too." - Dr. Turegano detailing the physiological mechanism linking psychological stress to acne breakouts.
• At 0:20:42 - "I always say the absence of evidence is not the evidence of absence." - Dr. Hyman addressing why nutrition and lifestyle interventions lack large double-blind randomized controlled trials due to a lack of financial incentives.
• At 0:22:54 - "Where we have the most evidence for acne, it's dairy and with sugar. When it comes to dairy, it's more so skim milk than it is whole milk, but the evidence is pretty compelling for really all forms of dairy." - Dr. Turegano identifying the primary dietary triggers supported by dermatological research for acne.
• At 0:27:25 - "We have a drastic drop in estrogen within the first five years of menopause, and estrogen is huge when it comes to just overall skin health." - Dr. Turegano explaining why menopausal hormone shifts lead to rapid collagen loss, dryness, and epidermal atrophy.
• At 0:38:23 - "I think of it like a mattress, you know, like the mattress cover is like our epidermis, and then the springs are like your dermis, and then the actual bed frame is, you know, your bone structure that's supporting everything." - Dr. Turegano providing a structural analogy for how the three layers of the skin and underlying bone age over time.
• At 0:41:30 - "Just because you take collagen peptides doesn't mean that that collagen goes to your skin. It's more so that the collagen peptides can send signals to help your body build better collagen." - Dr. Turegano clarifying the mechanism of action for oral collagen supplements.
• At 0:48:40 - "It's like only 40% of people can actually create their own like urolithin A. So—and urolithin A, we know, helps with mitophagy within your cells." - Dr. Turegano explaining why most people cannot naturally convert dietary polyphenols into the postbiotic urolithin A without supplementation.
• At 0:50:17 - "People don't understand that probably a third or a half of the metabolites in their bloodstream are from their gut microbiome. They're not made by your cells; they're made by these bacteria that are producing all these molecules." - Dr. Hyman highlighting the systemic reach of the gut microbiome in regulating human health and skin inflammation.
• At 0:59:56 - "What's interesting too, we have studies to show that low vitamin D can make melanoma—like can put you at higher risk for melanoma, which is kind of ironic, right? Because we say stay out of the sun to, you know, to prevent melanoma." - Dr. Turegano discussing the counterintuitive relationship between vitamin D status, sun exposure, and melanoma risk.
• At 1:07:20 - "PDRN stands for polydeoxyribonucleotide, and it's derived from salmon sperm. And most of the data is with PDRN injections into the skin. We know that it helps with collagen remodeling when it gets into the dermal layer; it helps with wound healing." - Dr. Turegano breaking down the origin and clinical evidence behind the popular K-Beauty ingredient PDRN.

Takeaways

• Adopt a Mediterranean Diet and Eliminate Acne Triggers: Cut out dairy (especially skim milk) and sugar to reduce acne flares and prevent collagen-damaging glycation (AGEs). Focus on a high-fiber, polyphenol-rich Mediterranean diet with adequate protein, vitamin C, and carotenoids (beta-carotene, lycopene, astaxanthin), and consider a 2-to-3-week gluten elimination trial if you suffer from psoriasis or dermatitis flares.
• Test Fasting Insulin and Omega-3 Levels: In addition to checking vitamin D and thyroid function, ask your doctor to test your fasting insulin and the ratio of insulin to fasting glucose—aiming for an optimal fasting insulin of less than 5 rather than the standard lab cutoff of 18. Additionally, target an Omega Index of over 8% by eating wild fish like sardines and salmon or supplementing with omega-3 fatty acids.
• Investigate Gut Overgrowths for Chronic Skin Conditions: If you have stubborn rosacea, acne, or psoriatic arthritis, work with a practitioner to evaluate and treat underlying SIBO, H. pylori, or fungal overgrowth. As demonstrated in Dr. Hyman's case study—where a patient resolved severe psoriatic arthritis, migraines, IBS, and depression in 6 weeks while losing 20 pounds—combining targeted gut therapy (such as rifaximin and an antifungal) with probiotics, zinc, fish oil, vitamin D, and an elimination diet can resolve systemic inflammation.
• Incorporate Resistance Training: Add strength training to your weekly exercise routine alongside cardio to improve insulin sensitivity, optimize fibroblast mitochondrial function, and directly thicken the collagen-rich dermal layer of your skin.
• Practice Smart Sun Protection: Protect your skin during peak UV hours (10:00 AM to 2:00 PM) using UPF clothing (as UV rays penetrate standard fabric) and mineral sunscreens or BEMT-based filters to prevent the 80% of extrinsic aging and skin cancers driven by UV radiation, while ensuring your vitamin D levels do not drop into a low-risk range.
• Implement an Evidence-Based Morning and Night Topical Routine: Follow Dr. Turegano's daily framework: in the morning, use a gentle cleanser, topical vitamin C (to fight oxidative stress from sun and pollution), moisturizer (with ceramides, hyaluronic acid, or niacinamide), and sunscreen. At night, apply a topical retinoid (such as OTC retinol, retinaldehyde, adapalene, or prescription tretinoin/tazarotene—avoiding use during pregnancy) alongside proven signaling peptides like topical GHK-Cu (copper peptides).
• Avoid Unproven Skincare Trends and Pore-Clogging DIYs: Skip using beef tallow or coconut oil on acne-prone skin as they are comedogenic and offer no sun protection, never apply acidic foods like lemon juice topically, and hold off on expensive injectable copper peptides or room-temperature exosome/stem cell treatments until rigorous human safety and stability standards are established.