I thought he looked good at his wedding, but in a short few months he seems to have morphed … but just shows we all have different tastes! After all, it’s why we have Mounds and Almond Joy.
What about Astaxanthin. Not only does it have proven benefits for the skin, but it is a potent antioxidant and the NIA ITP lists it as one of the tested molecules that extends life in mice (men only). And do a pubmed search to show other clinically proven benefits: brain health, exercise/muscle improvement, blood pressure, etc.
I asked Claude: “proven benefits of astaxanthin for skin”
Astaxanthin has several clinically supported skin benefits, primarily driven by its exceptional antioxidant potency — estimated to be up to 100x stronger than vitamin E.
Photoprotection
Oral astaxanthin accumulates in both the dermis and epidermis, where it reduces UV-induced reactive oxygen species and limits lipid peroxidation. Clinical trials using 4 mg/day showed a significant increase in minimal erythema dose (MED) — a measure of sunburn resistance — compared to placebo after 10 weeks. It also suppresses UV-induced matrix metalloproteinase-1 (MMP-1), an enzyme that breaks down collagen.
Wrinkles & Elasticity
Human studies at 6 mg/day for 6–8 weeks showed reductions in wrinkle depth and improvements in skin elasticity. Systematic reviews confirm moderate but consistent improvements in elasticity and hydration, though wrinkle effects are more variable across studies. Astaxanthin’s collagen-protective action is a key mechanism behind these results.
Skin Hydration & Barrier Function
Astaxanthin improves barrier function by reducing transepidermal water loss (TEWL) and increasing moisture content. Studies in The Journal of Dermatological Science found that daily supplementation improved skin resistance to UV damage and promoted hydration.
Pigmentation & Tone
Clinical evidence also shows reduced hyperpigmentation and age spots, leading to a more even skin tone. Continuous intake reverses age-related morphological changes in residual skin surface components, with effects especially pronounced in middle-aged subjects.
Practical Guidance
- Dose: 4–12 mg/day oral supplementation is the typical studied range
- Timeline: Benefits generally appear within 6–12 weeks
- Source: Algae-derived astaxanthin is preferred over synthetic forms
- Side effects: Generally well-tolerated; possible GI effects, minor bleeding risk, and blood pressure/glucose changes
Given your interest in longevity and skin aging, astaxanthin pairs well with other antioxidant protocols — it works synergistically with vitamin C and E for enhanced photoprotection.
Prepared using Claude Sonnet 4.6
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That’s the most unintentionally funny comment of the day. WTF there’s seriously people who don’t recognize Jeff Bezos’s ugly mug when they see it?
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It felt deserved that Attia turned into that after what he did.
Also would you believe that I image searched Bezos during writing this comment and had a feeling it was him but didn’t write it? Hahaha.
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Yes, I like astaxanthin. Take 12mg/d. Can’t say I’ve specifically noted any skin benefits, but I think that’s very difficult to tell given all the other factors (other skin treatments, plus the changing season etc).
Still, in theory, it offers some degree of photoprotection in terms of skin ageing, and therefore presumably some degree of skin cancer protection. I don’t think there has been any trial looking at that, but it seems plausible to me that if it increases resistance to sunburn, it should also protect from the damage which causes many cancers.
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UPDATE on estriol face cream experiment for myself (a male):
I did find the estradiol and estriol combo to have a more noticeable visual benefit for the skin compared to just estriol, but the long term hormonal effects for estradiol use concerned me.
I was using estradiol/estriol 1-2x a week. Didn’t experience any side effects.
This past week I used estriol on my face every night. I unfortunately need to report that I experienced sexual side effects. Erectile dysfunction and less sensitivity.
I stopped using the estriol on my face 2 nights ago and noticed improved erectile function, and expect full function to return within 1-2 weeks.
I’m going to take 25mg of Mesterolone (brand name: Proviron) daily for the next 2 weeks as well to counteract some of these side effects.
It’s unfortunate that estriol alone didn’t have the same effects as the combo of estradiol and estriol. I question if estriol even did anything. Perhaps it was just the estradiol.
Equally unfortunate is the fact that estriol use does not seem sustainable in a consistent fashion for men.
I wanted to report this as I felt it was useful data.
UPDATE 24 hours later: Erectile function has improved dramatically since ceasing estriol. A promising sign of quick recovery.
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RLS-1496 is an investigational, first-in-class, disease-modifying, selective glutathione peroxidase 4 (GPX4) modulator that targets pathologic senescent and other stressed, aging cells that drive chronic, age-dependent diseases, such as AK, and represents a novel drug category — Adaptive SenoTherapeutics
Preliminary RLS-1496 Actinic Keratosis Trial Results
- The Phase 1b/2a study of RLS-1496 showed a 46% reduction in AK count compared to 11% for untreated control at 4 weeks in the first 18 of 24 patients evaluated
- RLS-1496 was associated with favorable safety, with no serious adverse events (AEs) and no discontinuations due to AEs during the 4-week study
- RLS-1496 was well-tolerated, causing minimal local irritation, an area of high unmet need in the standard of care
- A Phase 2b dose-ranging AK study for RLS-1496 will begin in Q4
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I don’t want to be ‘that guy’ but can you discount placebo/nocebo effects?
Effects subsiding within 24h is way too fast for it to be attributable to those compounds IMO. If you truly raised systemic estrogens enough to alter your SHBG, testosterone and libido, they wouldn’t normalise that quickly.
Estriol is a weak estrogen and probably wouldn’t have much systemic effect. But estradiol is much stronger and also has a longer half life after transdermal application.
Also, as a random anecdote I actually note that I feel and function better with higher E2 than lower.
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It wasn’t placebo or nocebo. I wasn’t expecting it to cause erectile dysfunction. Effects began subsiding within 48 hours not 24, and symptoms have improved consistently since then.
I don’t plan on using it again, you can try it if you want and report the results.
E2 and E3 are not the same.
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I’m very glad you were willing to do the experiment and tell about the results. Thanks. I considered the potential for skin improvements with Estradiol cream some time ago, but decided “No Way Jose” after reading about the very likely to occur problem of systemic absorption.
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Now the question of what to do with the 6 tubes of estriol and 1 tube of estradiol cream I have lol.
You can send to me in the USA if shipping is not terribly expensive. We are having a shortage of of estrogen products and they can be difficult to come by
It would honestly be cheaper if you purchased it from where I got it. I got it from Maulik who is one of the popular sellers of Rapamycin on this website.
https://www.shreejiimpex.co.in/ is his website.
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Thanks, I’ll do that
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At this point as a male the only estrogen related thing I am interested in trying for skin health and longevity now is 17a estradiol.
Aromatase inhibition makes me feel bad, and topical estradiol and estriol haven’t worked for obvious reasons.
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https://x.com/jefftangx/status/2062225463905275973?s=20
From Gemini:
Product Identification and Source
The product shown in the image HJ5_ID5XoAEqk4d.jpeg is a customized prescription topical preparation utilizing ExoBlue™ , a specialized cosmetic compounding base manufactured by PCCA (Professional Compounding Centers of America).
Source Breakdown
-
Base Manufacturer: PCCA, headquartered in Houston, Texas. PCCA does not sell directly to consumers; instead, they supply proprietary bases and bulk chemical ingredients exclusively to licensed member compounding pharmacies.
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Dispensing Pharmacy: The actual dispensing source is an independent compounding pharmacy, as indicated by the truncated text “…Compounding Pharmac…” printed at the top of the container label in
HJ5_ID5XoAEqk4d.jpeg. The exact identity of the retail pharmacy cannot be determined because the header text is cropped out.
Base Composition and Mechanism
ExoBlue™ (PCCA Product #30-5290) is an advanced skin-conditioning vehicle designed to optimize peptide stability and facilitate multi-pathway skin rejuvenation. Rather than functioning as an inert carrier, the base itself is formulated with a framework of active cosmetic technologies:
PCCA+ 1
| Key Ingredient | Functional Profile |
|---|---|
| GHK-Copper Peptide PURE | Stimulates fibroblast proliferation and collagen synthesis; provides the cream with its inherent light blue tint. |
| Centella asiatica-Derived Exosomes | Act as nanometric cellular messengers to accelerate natural tissue repair pathways. |
| Acetyl Hexapeptide-8 | Minimizes muscle microtensions to smooth expression lines. |
| Zinc Hydrolyzed Hyaluronate | Delivers deep trans-epidermal hydration and supports barrier integrity. |
For detailed documentation, refer to the PCCA ExoBlue™ Product Page and the official PCCA Press Release.
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Beyond Chronology: Why Your Peers See You Differently and the Real Vectors of Facial Aging
Our chronological age is a fixed metric, but our biological age is highly variable, often written directly onto the canvas of our skin. A new study published in the Journal of Dermatologic Science and Cosmetic Technology uncovers a stark divergence between the age on a person’s birth certificate and how old they actually look to an audience of their peers. By deploying a panel of over 60 non-expert, adjacent-age assessors to review standardized digital photographs of 308 Chinese women aged 15–65, researchers mapped out the precise morphological features that govern human age perception.
The overarching finding challenges common assumptions: across the entire cohort, women were perceived as an average of 1.6 years older than their actual chronological age. However, this age distortion is highly non-linear across a lifespan. Chronologically younger women bear the heaviest burden of overestimation. Strikingly, teenagers in the 15–20 age group were judged to be an average of 5.6 years older than their true age. This overestimation tapers off mid-life, stabilized between ages 41–50 where perceived age aligns closely with reality. By contrast, an inversion occurs at the oldest end of the spectrum: women aged 61–65 were perceived as an average of 2.4 years younger than their chronological baseline.
What drives these perceptual shifts? The data reveals that humanity’s internal age-estimation algorithms rely on distinct spatial and surface cues. While deep architectural structural changes like nasolabial folds and marionette lines act as global anchors for aging across all generations, superficial skin quality dictates the fine-tuning of age estimation in older adults. In youth, minor deviations from flawless skin uniformity—such as early under-eye lines or localized sagging—trigger cognitive heuristics that sharply penalize the subject, making them appear prematurely aged to observers. Conversely, older individuals who manage to maintain superior skin radiance, smoothness, and an even complexion stand out as uniquely well-preserved, driving substantial age underestimation by their peers.
Actionable Insights
For longevity practitioners and biohackers tracking appearance as a proxy for biological vitality, this study provides clear directions on where to focus therapeutic and cosmetic interventions:
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Prioritize Mid-Face Structural Integrity Over Minor Eye Wrinkles: Marionette folds and nasolabial folds are the most heavily weighted features driving older age perception across all groups. Surprisingly, isolated markers like crow’s feet had a very low relative weight (ranking 17th out of 25 features), meaning treating them yields minor adjustments to how old you look.
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Target Skin Tone and Glycation Deficits After Age 40: For individuals over 40, skin dullness and skin yellowness increase the risk of looking older by an effect size of 33% (Odds Ratio: 1.11–1.21) and 34% (Odds Ratio: 1.23–1.46) respectively. In the oldest cohort (61–65), skin dullness increases the odds of looking older by 68%. Interventions should focus on preventing advanced glycation end-products (AGEs) and boosting dermal microcirculation.
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Younger Cohorts Must Prevent Mid-Face Sagging and Under-Eye Lines: For individuals aged 15–20, the presence of under-eye wrinkles increases the odds of looking older by more than two-fold (Odds Ratio: 2.38). Overall facial sagging similarly doubles the odds of appearing older (Odds Ratio: 2.04). Protecting the delicate sub-orbital extracellular matrix in early adulthood is paramount.
Source:
- Open Access Paper: An exploration study on the relationship between chronological and perceived age in Chinese women with systematic validation of a new method for perceived age determination
- Institution: Beiersdorf Innovation Center Shanghai.
- Country: China.
- Journal Name: Journal of Dermatologic Science and Cosmetic Technology.
- Impact Evaluation: The impact score of this journal is not yet officially rated or widely indexed with a standard high Impact Factor due to its recent launch in the 2024–2026 window, therefore this is a Low impact journal.
Study Design Specifications
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Type: In vivo observational cohort study with clinical grading and cross-sectional photographic peer evaluation.
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Subjects: 308 healthy Chinese female participants who fully completed the protocol (out of 314 originally enrolled; 6 dropped out due to personal reasons). Subjects were distributed across ten distinct 5-year chronological age intervals from 15 to 65 years old, ensuring at least 30 subjects per bracket.
Biomarker Strength: Correlation with Perceived Age
Spearman correlation coefficients (ρ) quantify the strength of the relationship between clinical structural degradation and peer-perceived age:
- Crow’s feet wrinkles: ρ=0.875 (Very Strong)
- Marionette fold severity: ρ=0.844 (Very Strong)
- Underneath eye wrinkles: ρ=0.835 (Very Strong)
- Inter-ocular wrinkles: ρ=0.824 (Very Strong)
- Middle-face cheek fold: ρ=0.819 (Very Strong)
- Upper-lip wrinkles: ρ=0.813 (Very Strong)
- Fine lines on the forehead: ρ=0.810 (Very Strong)
- Forehead wrinkles (deep): ρ=0.752 (Strong)
- Nasolabial fold depth: ρ=0.768 (Strong)
- Dropping of upper outer eyelid: ρ=0.744 (Strong)
- Glabellar wrinkles: ρ=0.662 (Moderate-Strong)
- Eye Bags: ρ=0.368 (Weak)
Critical Limitations
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Extreme Geographical and Climatic Isolation: A major flaw is that the entire cohort was pulled from a single metropolitan region (Guangzhou, China). This restricts the findings to a population exposed to a specific high-humidity, subtropical environment. It fails to account for how alternative UV baselines, pollution variations, or diverse national skin phenotypes alter aging trajectories.
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Subjective Scaling and Lack of Absolute Biological Clocks: The research relies entirely on visual grading atlases and subjective questionnaires. It completely lacks objective validation against hard biological aging metrics.
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Inherent Assessor Selection Bias: Utilizing peer assessors who are actively participating in a facial appearance study introduces an observer-expectancy bias. These individuals are likely hyper-attentive to structural flaws compared to the general public, potentially inflating the recorded age overestimations.
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Commercial Conflict of Interest: The entire study was funded, designed, and executed by personnel employed by the Beiersdorf Innovation Center Shanghai (the parent conglomerate behind major global skincare brands).
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The biggest collagen study yet reveals what actually works
A massive review of collagen research found that the supplements can improve skin elasticity and hydration while helping reduce osteoarthritis pain and stiffness.
Collagen Supplementation for Skin and Musculoskeletal Health: An Umbrella Review of Meta-Analyses on Elasticity, Hydration, and Structural Outcomes . Aesthetic Surgery Journal Open Forum , 2026; 8 DOI: 10.1093/asjof/ojag018
the following supplement was identified by Google Gemini as helpful to prevent skin aging in this query cited here: What are the best strategies to maintain your early 20s appearance for as long as possible? - #3 by RapAdmin
Google Gemini Information Summary:
Oral Polypodium Leucotomos Extract (PLE) — Evidence Summary
What It Is
Polypodium leucotomos is a tropical Central American fern whose dried leaf extract is rich in phenolic acids (caffeic, ferulic, chlorogenic, and cinnamic acids) — potent antioxidants that confer systemic photoprotection when taken orally.
Mechanisms of Action
PLE works through multiple complementary pathways relevant to skin health and longevity:
Photoprotection & UV Defense: Neutralizes UV-generated reactive oxygen species (ROS), reducing oxidative DNA damage (cyclobutane pyrimidine dimers). A landmark 1997 study in Photodermatology, Photoimmunology & Photomedicine demonstrated that oral PLE prevented acute sunburn, psoralen-induced phototoxic reactions, and — critically — depletion of Langerhans cells, the skin’s frontline immune sentinels.
Anti-Photoaging: Inhibits matrix metalloproteinase-1 (MMP-1), preserving collagen and elastin — the structural proteins degraded by chronic UV exposure and responsible for wrinkles and skin laxity. It also blocks trans-urocanic acid isomerization (an immunosuppressive UV byproduct) and UV-mediated apoptosis and necrosis.
Immunomodulation: Preserves cutaneous immune surveillance by protecting Langerhans cells, which are rapidly depleted by UV — a key mechanism behind UV-induced immune suppression and skin cancer risk.
Clinical Evidence (Level 2 — RCTs)
| Study | Design | Key Finding |
|---|---|---|
| Middelkamp-Hup et al. (2004) JAAD | RCT, n=9, skin types II–III | Oral PLE significantly reduced erythema, sunburn cells, DNA damage, and mast cell infiltration vs. placebo |
| González et al. (2017) JAAD | Human clinical study, UVB response | PLE increased minimal erythema dose (MED); 17/22 subjects showed decreased UVB-induced changes |
| Parrado et al. (2025) Nutrients | RCT, double-blind, 8 weeks | 23.8% increase in MED + 46.2% reduction in erythema intensity in treatment group |
| Choudhry (2014) | RCT, vitiligo patients | Improved repigmentation when combined with NB-UVB |
| Gonzalez et al. (1997) Photoderm | RCT | Prevented Langerhans cell depletion and psoralen phototoxicity |
A 2025 systematic review in Journal of Drugs in Dermatology (21 studies meeting criteria, 11 RCTs) concluded PLE shows “strong evidence of effectiveness” across photoprotection, photoaging, and skin cancer prevention applications.
An ongoing NIH-registered clinical trial (NCT02813902) is investigating PLE specifically for prevention of skin cancer and its precursors.
Clinical Utility for Skin Longevity
PLE is not a sunscreen replacement — it provides an SPF equivalent of roughly 3–5 — but its value is systemic: it addresses UV damage in areas topical sunscreen misses or fails (incomplete coverage, missed reapplication), and it targets the immunosuppressive and pro-aging molecular pathways that drive long-term photoaging and carcinogenesis. Typical evidence-backed dosing is 240–480 mg/day, taken before sun exposure.
Reputable Products
Heliocare — The gold standard brand, built on proprietary Fernblock® PLE technology, extensively used in clinical research. Widely available via dermatologist offices, Amazon, and pharmacies. 240 mg/capsule.
Heliocare Ultra — Higher-dose formulation (480 mg PLE equivalent) with additional antioxidants for higher-risk individuals.
Supersmart Polypodium Leucotomos Extract — 1,000 mg/day dose (500 mg per capsule); manufactured in GMP/HACCP-certified facilities; 30+ year established supplement company.
Nutricost Polypodium Leucotomos Extract — 250 mg of a 20:1 concentrate (equivalent to 5,000 mg whole leaf); NSF-certified, GMP-compliant, FDA-registered facility. Budget-accessible.
NusaPure Polypodium Leucotomos — 240 mg, 10:1 extract; cGMP-manufactured in the USA; non-GMO, vegan.
Note: Heliocare is the most clinically referenced brand by name in dermatology literature and is the product most often recommended by dermatologists specifically because its Fernblock® extract is the standardized form used in many published trials.
Sources:
- Topical or oral PLE prevents Langerhans cell depletion — PubMed (1997)
- Oral PLE decreases ultraviolet-induced damage — PubMed (2004)
- Impact of oral PLE on UVB response — PMC/JAAD (2017)
- 8-Week RCT: Red Orange + PLE on UVB skin responses (2025)
- Fernblock: Molecular Mechanisms & Photoaging Review — PMC
- Clinical Efficacy & Safety of Oral PLE — Systematic Review, SKIN Journal
- Utility of Oral PLE for Dermatologic Diseases — JDD 2025
- Oral PLE for photodermatoses, 57 patients — PubMed
- NIH Clinical Trial: PLE in Skin Cancer Prevention (NCT02813902)
- Combination oral + topical PLE vs. actinic keratosis — Wiley 2023
- Heliocare on Amazon
- Nutricost PLE
Here’s a pricing summary for each product, with direct purchase links:
| Product | Dose / Count | Approx. Price | Buy Link |
|---|---|---|---|
| Heliocare (standard) | 240mg Fernblock®, 60 caps | ~$37 retail / ~$25 with coupons | Amazon · LovelySkin |
| Heliocare Ultra | 480mg Fernblock® + vitamins C/E, lutein, lycopene, 30 caps | ~$40–$42 | Dermacare Direct · Amazon |
| SuperSmart PLE | 1,000mg (4:1 extract), 90 veg caps | ~$19 | SuperSmart Direct · Walmart · Target |
| Nutricost PLE | 250mg (20:1 extract = 5,000mg equivalent), 240 caps | ~$15–$17 | Nutricost.com · Amazon |
| NusaPure PLE | 240mg (10:1 extract = 2,400mg equivalent), 200 veg caps | ~$18–$22 | NusaPure Direct · Amazon |
Value note: Nutricost and SuperSmart offer the best cost-per-dose for budget-conscious buyers. Heliocare commands a premium as the clinically referenced brand with standardized Fernblock® extract — worth it if you want the formulation closest to what was studied in RCTs.
Sources:
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