Move over retinol: a safer, non-irritating, non-sensitizing, non-carcinogenic, non-teratogenic, non-toxic alternative that is scientifically proven to be just as effective for anti-aging is here: bakuchiol (buh-COO-chee-y’all).
Bakuchiol is derived from the babchi seed, a classical herb used in Chinese medicine (Psoralea corylifolia, or Bu Gu Zhi in TCM) so I have been geeking out over learning everything I can about this ingredient since I am a lover of all things TCM (it gave me my life back, after all). It has also classically been used in Ayurvedic medicine.
This ancient plant has been used for thousands of years to reduce inflammation and treat a number of skin conditions, including psoriasis, leukoderma and vitiligo, eczema, and even leprosy (Alam, Khan, & Asad, 2018).
Not only that, but bakuchiol in skincare has been shown in the scientific literature to reduce the appearance of lines and wrinkles, even skin tone and reduce hyperpigmentation, minimize the appearance of pores, make skin look and feel firmer, give skin a bright, glowing, radiant look, reduce redness and inflammation after sun exposure, and even reduce the severity of acne (Alam et al., 2018; R. Chaudhuri, 2015; R. K. Chaudhuri & Bojanowski, 2014; R. K. Chaudhuri & Marchio, 2011; Dhaliwal et al., 2019)
Basically: it can do everything retinol can do, but better, since it carries none of the risks of retinol.
The Dangerous Truth About Retinol and Retinoids
What is retinol?
Retinol and other retinoids are derivatives of Vitamin A which have long been popular in anti-aging skincare because, put simply, they do work at reducing fine lines, wrinkles, pores, and hyperpigmentation and increasing collagen synthesis.
Retinoids to avoid in over-the-counter skincare products include: retinol, retinyl palmitate, retinyl acetate, retinyl linoleate, retinyl propionate, and hydroxypinacolone retinoate. Prescription retinoids include adapalene (Differin), tazarotene (Tazorac), tretinoin (Retin-A), and isotretinoin (Accutane).
Is retinol safe?
Retinol and other retinoids “evoke substantial irritating side effects, including pain and inflammation” (Yin et al., 2013) and cause red, dry, irritated, itchy, red, sensitive skin, known as the “retinoid reaction” or more formally, “retinoid dermatitis”, and experts think this is in part due to the fact that retinol upregulates pro-inflammatory cytokines, especially MCP-1 and IL-8 (Dhaliwal et al., 2019; Kim, Lee, & Kang, 2003).
Interestingly, both naturally occurring and synthetic retinoids (including retinol) activate the same irritant receptor in the skin as capsaicin. You know, the pungent ingredient in chili pepper that causes a burning sensation? Yeah, retinol activates that same receptor in your skin! Transient receptor potential channel vanilloid subtype 1 (TRPV1), for my fellow science geeks (Yin et al., 2013).
Even more worrisome is that according to an FDA study conducted at the National Center for Toxicological Research, retinoids, including retinol, promote tumor formation when the skin is exposed to UV radiation (and yet sunscreen manufacturers in the US continue to add it to formulas). Retinol and other retinoids also have the capacity to cause devastating birth defects by contributing to excessive daily vitamin A intake and are NOT safe to use during pregnancy or breastfeeding. (National Toxicology Program, 2012)
The Environmental Working Group (EWG) Skin Deep Database rates retinol as a 9 as one of the most dangerous ingredients allowed into products.
Unfortunately many skincare companies are guilty of “greenwashing” (using deceptive language to make the consumer believe that the product is safe and non-toxic) their products that contain retinol. There are many otherwise clean brands that get an F in my book for including retinol or other retinoids in their skincare products.
My friend Lindsay over at The Rogue Pharmacist called it retiNOPE which is now what I am going to start calling it!
Bakuchiol as a Safe Retinol Alternative
In 2018 a randomized, double-blind trial comparing bakuchiol to retinol that was conducted at UC Davis was published in the British Journal of Dermatology. The incredible results?
“Bakuchiol and retinol both significantly decreased wrinkle surface area and hyperpigmentation, with no statistical difference between the compounds.” (Dhaliwal et al., 2019)
Bakuchiol was EQUALLY as effective as retinol as an anti-aging ingredient. Amazing!
This study tracked 44 participants aged 31-56 for 12 weeks and measured wrinkles, pigmentation, and tolerability of the two compounds.
Bakuchiol significantly reduced the surface area involvement of fine wrinkles, decreasing them by 5% at 4 weeks, 6.4% at 8 weeks, and a whopping 19% at 12 weeks.
59% of the participants in the bakuchiol group saw a significant reduction in hyperpigmentation at week 12, which the authors think is due to a combination of bakuchiol’s known antioxidant effects and its ability to disrupt the melanin synthesis pathway.
And even though bakuchiol performed just as well as retinol, it was MUCH better tolerated and did not cause stinging or burning. The study authors think that this may be due to bakuchiol’s potent anti-inflammatory effects. It is an analogue of the well-known and well-studied antioxidant resveratrol, after all (Chen et al., 2010).
This UC Davis study supports the results of an earlier study published in 2014 that found
That 2014 study also showed that bakuchiol regulates a wide range of genes related to aging, upregulating things like collagens, elastin, and fibronectin (involved in reducing the appearance of wrinkles and improving firmness/elasticity), hyaluronans and aquaporin 3 (involved in maintaining appropriate hydration, elasticity, and barrier function), and many more.
Bakuchiol and Swiss Alpine Rose as RetiNatural Complex
Clearly bakuchiol is a powerful ingredient all on its own, but the green chemists at Beautycounter took things a step further and paired it with Swiss Alpine Rose (Rhododendron ferrugineum) to make what they call RetiNatural Complex.
Think of bakuchiol doing the heavy lifting to repair skin while Alpine rose protects it from daily environmental stressors. The interesting thing about this flower is that it grows in extraordinarily challenging conditions at the highest altitudes in the Alps, protecting itself remarkably well against dehydration. Used in skincare, it inhibits age-related oxidative damage (i.e. it is an antioxidant).
Bakuchiol and Swiss Alpine Rose, two powerful and exotic natural plant ingredients, can be found in the brand new, totally groundbreaking age-prevention and age-reversal line called Countertime. Incredibly, every single product in the skincare line contains RetiNatural, a testament to how safe and gentle it is and also speaks to the incredible value of the line, since every product has these powerful actives.
My Honest Countertime Review and Results
I was part of a small group of people allowed to try a preview set of the Countertime cleansing oil, essence, tripeptide serum, and tetrapeptide supreme cream at the end of May 2019. I used it for the first time on May 30th and noticed positive changes in my skin the very next day.
I woke up to my skin feeling incredibly soft and smooth and with a subtle glow to it. I could tell immediately how potent these products are!
Each week my skin has continued to both look and feel better. I am actually in awe of just how soft and smooth my skin is. I didn’t think that much could happen to improve on my skin’s condition since I have been so diligent with my facial gua sha (learn how to do it here), nutrient-dense diet, and previous skincare regimen that included a hybrid of Countermatch adaptive moisture products and 5YINA hydrolat and facial oil made with Traditional Chinese Medicine herbs for anti-aging.
I mean, I was already constantly getting compliments on my skin, so I thought I was doing the best I could to care for it. Boy was I wrong!
I’ve been using the full collection (including the antioxidant soft cream and eye cream) since the last week of June and I am so in love. I have absolutely noticed that the fine lines on my forehead are less visible. And I think my skin is the most radiant it has ever been.
I am hoping that with a few more weeks of use I will see fading of hyperpigmentation right below my hairline. It’s subtle, but I notice it there, and based on all of these papers I’ve referenced, after 12 weeks I should be able to notice a reduction.
Here is me, photo taken today after 6 weeks of using Countertime. No filter. No makeup. Two small PMS blemishes, because hey, this is real life.
Here are some photos tracking my progress from before using Countertime to today. Forgive my expression in the first photo; it was taken pre-gua sha and I always take those photos with a completely relaxed face so I can see the sculpting and reduction in inflammation.
You can see in the photos that my frown lines are less visible! And look at how much less red my complexion is now. And check that freckle on my nose…WAY less visible now! Wow!
Beautycounter Countertime FAQs
Why do you like Beautycounter so much?
In short, Beautycounter values the safety of the ingredients in their products just as much as performance. No other company out there (that I am aware of) is as obsessed with scientific safety data of their ingredients, refusing to use more than 1500 ingredients known or suspected to be harmful to human health (aka The Never List). They take the European Union’s list of 1400 banned or restricted ingredients and add to it (bewilderingly, the US only partially restricts 30 ingredients…)
Beautycounter is a certified B Corporation (kind of like a non-profit on steroids) meaning they use profits to do good in the world, and must adhere to the highest standards of verified social and environmental performance, public transparency, and legal accountability to balance profit and purpose.
Beautycounter has a partnership with Dr. Ana Soto’s lab at Tufts University to study new clean beauty ingredients. Dr. Soto is a highly-regarded expert in the field of endocrine disrupting chemicals and her work was instrumental in getting BPA phased out of plastic consumer goods like baby bottles.
In 2018 our CEO Gregg Renfrew was honored by Goldman Sachs as an innovative entrepreneur, FastCompany named us one of the top 50 most innovative companies, and Google announced that we were the top trending beauty brand of 2018. Bono is one of our investors, too!
I could go on and on but I won’t….let’s talk about Countertime! Email me if you want more info or have questions, though.
What is Countertime and what about the Rejuvenating line?
Countertime is the revolutionary new age-prevention and age-reversal line from my favorite safe and high-performance skincare and cosmetics company Beautycounter. It has been in development for 3 years (that’s as long as I have been partnered with them!) and reflects the most cutting-edge research on SAFE and EFFECTIVE anti-aging skincare.
It is going to replace the current anti-aging line called Rejuvenating (now on the Last Chance section of the site) so either stock up or make the switch to Countertime (I promise you’ll love making the switch!)
What are the safe anti-aging ingredients in Countertime?
Bakuchiol and Swiss Alpine Rose extract, combine to make RetiNatural Complex - I already explained these ingredients in detail above, but in short they provide all of the anti-aging benefits of retinol with NONE of the concern or harm.
Tripeptide and tetrapeptide - peptides are super interesting to me because they each have a very specific function to address some sort of structural issue with the skin. For example, the tripeptide in this line very specifically targets vertical lines and wrinkles. Our bodies use peptides as messengers and they tell the skin when there has been damage that needs to be healed. When you apply exogenous peptides (i.e. in skincare) they kind of trick your skin into thinking there has been an injury that needs to be healed, which is why they stimulate collagen synthesis and even hyaluronic acid production.
Amino acids - help protect skin from damaging environmental stressors (pollution, UV exposure, weather, etc.) that lead to aging, while helping skin maintain optimal levels of hydration.
Fermented sugars - help soothe skin and slow the effects of aging by optimizing hydration. Dehydrated skin = prematurely aged skin.
Persian silk tree extract - Proven in independent clinical studies to brighten the eye area, fade dark circles, diminish puffiness, and reduce the appearance of crow’s feet. It also has six times the free-radical scavenging power of vitamin C - that is powerful! (Jung et al., 2003)
Nasturtium flower extract - reinforces the skin barrier, provides potent oxygenation, and protects the skin from drying environmental stressors (Jakubczyk, Janda, Watychowicz, Łukasiak, & Wolska, 2018)
Who can use Countertime?
I’ve been told by an aesthetician that it is prudent to begin an age-prevention skincare regimen in your mid to late 20’s. I didn’t start until I was 32 and seriously regret it since my skin used to be a hot mess before. Once we are in our 20’s, collagen production in the skin decreases by about 1% each year (Ganceviciene, Liakou, Theodoridis, Makrantonaki, & Zouboulis, 2012) which is why it makes sense to be proactive instead of reactive to the inevitable passage of time and aging process we will all see happen in our skin.
This isn’t about stopping time, it’s about feeling good about yourself and taking the best care of your body that you can. Nobody wants to look much older than they really are, and using skincare is one part of the equation for taking great care of your skin so that it both looks and feels the best it possibly can at any age.
Countertime works best with normal to dry skin, but it can work for oily skin as well. Here are my suggestions based on skin type:
Normal to dry skin - this line was designed for you! I recommend the full collection, but if you are on a budget or want to slowly introduce the products, the top 3 I would prioritize are the tripeptide serum, supreme cream, and mineral essence.
Combination/oily/oily and acne-prone skin - use a more clarifying cleanser, like the Countercontrol Clear Pore Cleanser (read my article about this incredible acne treatment line here) or Charcoal Bar (which you can get free this month for becoming a Band of Beauty member). You may need to skip the Supreme Cream (night cream) and use the Soft Cream (day cream) for AM & PM. You may also want to use a true toner in place of the mineral essence, like the Counterman Toner Pads (they can work well for women with this skin type, I promise).
Normal to dry skin that is very sensitive - This line is designed to be gentle enough for sensitive skin. That said, the one product in this collection you will want to go slowly with is the serum. Spot test it before using it all over your face. You may want to start using it only at night and work up to using it twice a day.
Normal skin with an oily T-zone - this collection will work for you, but if you feel you need a more clarifying cleanser choose one of the ones mentioned above. I’d suggest adding in the Balancing Charcoal Mask a few days per week as well, focusing on the T-zone.
Dry skin with acne - this is a tricky skin type that needs lots of TLC and patience. I know that with acne there is a tendency to want to use very stripping, drying products which isn’t appropriate for dry skin (only oily skin with acne). I would use everything except the soft and supreme creams and use the No 3 Balancing Facial Oil as your moisturizer instead. Consider using the Overnight Resurfacing Peel a few nights a week as a treatment in place of the serum. The SOS Acne Spot treatment is also amazing for preventing blemishes from becoming severe and helping them heal faster.
These are general suggestions, but there is no such thing as one-size fits all for skincare. I’d love to give you a complimentary 1:1 consultation based on your unique skin history, current product usage, and top skin concerns. I’ll help you come up with a regimen that fits your budget. Just fill out my skincare consultation form and I’ll get back to you as soon as I can!
Which products are in Countertime and how do you use them?
Let’s take a walkthrough of the products, shall we? First I want to draw your attention to the packaging - just LOOK at how gorgeous it is! Not to mention this pretty frosted glass is more easily recyclable and is sourced from North America. Using glass instead of plastic reduced the line’s greenhouse gas footprint by an estimated 38%!
Any complete skincare regimen, no matter the brand, has 4 steps: cleanse, prep, treat, and protect.
Step 1: Cleanse
This isn’t like other oil cleansers you’ve used, since it transforms into a milky cleanser when you add warm water, which activates sugar-based surfactants. It feels kind of like a hybrid between a traditional oil cleanser and a foaming cleanser. It leaves my skin feeling so clean yet not at all stripped of moisture.
Use 1 or 2 pumps and rub it into the skin for about 30 seconds, get your fingers wet with warm water to mix and form a milky texture, massage again, then wipe away with a soft cloth dampened with warm water. Pat face dry with a clean towel.
Features gentle sugar-based surfactants that activate when you add warm water
Easily removes face and eye makeup
Doesn’t disrupt the skin’s lipid surface, leaving the moisture barrier intact
Leaves skin feeling healthy, soft, and smooth, not stripped or dry
Rinses away clean, leaving no residue, allowing skin care applied afterwards to optimally absorb
Leaves skin looking radiant, luminous, and glowing
Skin looks brighter
Ophthalmologist tested; safe for contact lens wearers
Step 2: Prep
This is the first essence in the Beautycounter lineup! Essences are very popular in Korean skincare and becoming more popular here in the West, but they act as a replacement for toner and preps the skin to better absorb the serum and moisturizer. It is lightweight and deeply nourishing, like a shot of nutrition for the skin.
To use, shake a few drops into the palm of your hand and rub your hands together. Gently press it into your face and neck, and allow it to dry briefly.
Delivers a boost of hydration
Helps minimize the appearance of pores
Leaves skin looking luminous
Prepares skin to better absorb benefits of following skin care steps
Step 3: Treat
If you only get one thing from this line, I’d make it this serum. The specific tripeptide in it specifically targets vertical lines (frown lines aka “elevens” or “number ones”, marionette lines, nasogenian fold) as well as crow’s feet after 6 weeks of use (source). I encourage you to click that so you can SEE the results of this peptide!
To use, massage 1 or 2 pumps into your face and neck using upward strokes. Do not use too much or it may pill when you apply moisturizer or makeup. I find that 1 pump is more than enough for my whole face and neck.
As a whole, this serum:
Visibly increases skin firmness
Layers well with other products
Increases skin elasticity
Improves skin barrier function
Does not leave skin feeling tacky or sticky
Step 4: Protect (AM)
They ain’t lying with this name: this cream is soft. It is the heaviest day cream I have ever used and I initially thought that it was too heavy for me right now, since it is the peak of summer and the humidity is usually around 5000% here in Memphis.
I experimented and learned that it, along with the serum and essence underneath it, provide my skin enough moisture and lubrication that I can do gua sha on my face without needing to put a facial oil on top.
When I do this, the soft cream absorbs PERFECTLY into my skin. It also means I cannot skimp on my daily gua sha ritual! If you have dry skin, this moisturizer should feel perfect and you will likely still need to use an oil to do gua sha. You should NEVER feel harsh friction when doing gua sha. If you’re unsure, ask me!
To use, dispense 1 or 2 pumps and massage into the face and neck.
Features nasturtium flower extract to reinforce the skin barrier, provide potent oxygenation, and protect the skin from drying environmental stressors (Jakubczyk et al., 2018)
Fermented sugars soothe the skin and optimize hydration
Increases skin plumpness
Decreases the appearance of fine lines and wrinkles
Layers well under makeup
Step 4: Protect (PM)
MY FAVORITE PRODUCT! You know, maybe this should be the one thing you get from this collection. It is pretty darn amazing and absolutely worthy of the name “supreme”. Plus the value is tremendous since a little tiny bit goes a LONG way. I think my jar will last me 6 months or more. The sample set I was given was supposedly a one month supply, and by one month I was not even ⅓ of the way through the jar! It’s nice that Beautycounter tends to dramatically underestimate just how long their highly concentrated products last.
The tetrapeptide in this cream has been shown to stimulate collagen, hyaluronan, and fibronectin, which is associated with a significant reduction in wrinkles and roughness (Farwick et al., 2011).
To use, massage a pea sized (or smaller) amount into your face and neck. Do not overuse as this can lead to pilling. You’ll be surprised how little is needed to moisturize your skin.
Supremely rich and luxurious texture, meant to compete with $300 a jar Creme De La Mer
Visibly increases skin firmness
Smooths skin texture to minimize fine lines and wrinkles
Does not pill when layering
Incredibly hydrating yet not heavy and readily absorbed
I LOVE that this product does not contain caffeine, which I react poorly to in eye creams. It has a fascinating ingredient (like all the other actives - ha!): Persian silk tree extract, which has been proven in independent clinical studies to brighten the eye area, fade dark circles, diminish puffiness, and reduce the appearance of crow’s feet.
To use, apply a tiny dab to your ring finger and rub both ring fingers together. Gently pat the eye cream on your orbital bone underneath the eye and on the outsides of your eye. It is not meant for your eyelids, only the undereye area/crow’s feet area.
Brightens eye area
For an added soothing and cooling effect, put the Countertime Ultra Renewal Eye Cream in your refrigerator before use
Eye are feels instantly hydrated
Layers easily with concealer
Tip: don’t apply your moisturizer too close to your eyes; you want the eye cream to have contact with your eye area, and your facial moisturizer with the rest of your face. Eye creams are less effective when layered on top of another moisturizer because they can’t penetrate the skin as well.
How can I do gua sha with Countertime?
First off, if you’re like “gwahh, whaaat??”, read my in-depth blog post about this Chinese medicine health and wellness practice that has significant skin benefits.
Yes, you can absolutely do gua sha while using Countertime. Since my skin is not very dry AND these products are the most hydrating Beautycounter has ever released, I have found that I don’t need to use a facial oil to do gua sha.
BE VERY CAREFUL DOING GUA SHA WITHOUT AN OIL.
I was surprised that I didn’t need one, but the products provide adequate hydrating and “slip” so that my tool glides effortlessly over my skin when I do gua sha immediately after applying my daytime products.
You should NOT feel any friction or tugging. The tool MUST glide smoothly and feel lubricated.
As for which oil to use, if you are looking for extra help fading dark spots and extra antioxidant protection, use No 1 Brightening Facial Oil.
For extra anti-aging benefits and plumping, use No 2 Plumping Facial Oil.
For acne-prone or oily skin or redness, use No 3 Balancing Facial Oil.
What about the Overnight Resurfacing Peel?
I’ll tell you something incredible: since starting Countertime I have gone from NEEDING the Peel 4-5 nights a week to only needing it about once a week.
If you have oily skin, acne, or want an extra boost at fading hyperpigmentation or scars, then you’ll want to continue to incorporate the Peel 2 to 3 nights a week, replacing the serum when you use the Peel (the Peel is a treatment, so it always replaces the serum in your regimen).
Have more questions? Need help? I am here for you! Send me an email, fill out my skincare consultation for personalized recommendations, or leave a comment below.
If you’re interested in non-toxic skincare and cosmetics make sure you join my Clean Beauty Community. We’re on Instagram (it’s private so that I can keep you in the loop about my special offers and deals), Facebook, and I even have a dedicated newsletter for this.
Alam, F., Khan, G. N., & Asad, M. H. H. B. (2018). Psoralea corylifolia L: Ethnobotanical, biological, and chemical aspects: A review. Phytotherapy Research: PTR, 32(4), 597–615. https://doi.org/10.1002/ptr.6006
Chaudhuri, R. (2015). Bakuchiol: A Retinol-Like Functional Compound, Modulating Multiple Retinol and Non-Retinol Targets. In Cosmeceuticals and Active Cosmetics, Third Edition (pp. 1–18). https://doi.org/10.1201/b18895-2
Chaudhuri, R. K., & Bojanowski, K. (2014). Bakuchiol: a retinol-like functional compound revealed by gene expression profiling and clinically proven to have anti-aging effects. International Journal of Cosmetic Science, 36(3), 221–230. https://doi.org/10.1111/ics.12117
Chen, Z., Jin, K., Gao, L., Lou, G., Jin, Y., Yu, Y., & Lou, Y. (2010). Anti-tumor effects of bakuchiol, an analogue of resveratrol, on human lung adenocarcinoma A549 cell line. European Journal of Pharmacology, 643(2-3), 170–179. https://doi.org/10.1016/j.ejphar.2010.06.025
Dhaliwal, S., Rybak, I., Ellis, S. R., Notay, M., Trivedi, M., Burney, W., … Sivamani, R. K. (2019). Prospective, randomized, double-blind assessment of topical bakuchiol and retinol for facial photoageing. The British Journal of Dermatology, 180(2), 289–296. https://doi.org/10.1111/bjd.16918
Farwick, M., Grether-Beck, S., Marini, A., Maczkiewitz, U., Lange, J., Köhler, T., … Krutmann, J. (2011). Bioactive tetrapeptide GEKG boosts extracellular matrix formation: in vitro and in vivo molecular and clinical proof. Experimental Dermatology, 20(7), 602–604. https://doi.org/10.1111/j.1600-0625.2011.01307.x
Ganceviciene, R., Liakou, A. I., Theodoridis, A., Makrantonaki, E., & Zouboulis, C. C. (2012). Skin anti-aging strategies. Dermato-Endocrinology, 4(3), 308–319. https://doi.org/10.4161/derm.22804
Jakubczyk, K., Janda, K., Watychowicz, K., Łukasiak, J., & Wolska, J. (2018). Garden nasturtium (Tropaeolum majus L.) - a source of mineral elements and bioactive compounds. Roczniki Panstwowego Zakladu Higieny, 69(2), 119–126. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/29766690
Jung, M. J., Chung, H. Y., Kang, S. S., Choi, J. H., Bae, K. S., & Choi, J. S. (2003). Antioxidant activity from the stem bark of Albizzia julibrissin. Archives of Pharmacal Research, 26(6), 458–462. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/12877554
Kim, B.-H., Lee, Y.-S., & Kang, K.-S. (2003). The mechanism of retinol-induced irritation and its application to anti-irritant development. Toxicology Letters, 146(1), 65–73. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/14615068
National Toxicology Program. (2012). NTP TECHNICAL REPORT ON THE PHOTOCOCARCINOGENESIS STUDY OF RETINOIC ACID AND RETINYL PALMITATE. Retrieved from National Institutes of Health website: https://ntp.niehs.nih.gov/ntp/htdocs/lt_rpts/tr568_508.pdf
Yin, S., Luo, J., Qian, A., Du, J., Yang, Q., Zhou, S., … Hu, H. (2013). Retinoids activate the irritant receptor TRPV1 and produce sensory hypersensitivity. The Journal of Clinical Investigation, 123(9), 3941–3951. https://doi.org/10.1172/JCI66413