The Real Science Behind “Anti-Aging” Beauty Products
The beauty industry heavily hypes the nascent promise of stem cells for rejuvenation.
The beauty market abounds with high-end creams and serums that claim the use of stem cells to rejuvenate aging skin.
Selling on the internet and at department stores like Nordstrom, these products promise "breakthrough" applications to plump, smooth, and "reverse visible signs of aging," and at least one product offers to create a "regenerative firming serum, moisturizer, and eye cream" from customers' own stem cells – for a whopping $1200.
The beauty industry is heavily hyping glimmers of the nascent field of stem cell therapy.
Steeped in clinical-sounding terms like "proteins and peptides from pluripotent stem cells," the marketing of these products evokes a dramatic restoration of youthfulness based on cutting-edge science. But the beauty industry is heavily hyping glimmers of the nascent field of stem cell therapy. So what is real and what's not? And is there in fact a way to harness the potential of stem cells in the service of beauty?
Plant vs. Human Stem Cells
Stem cells do indeed have tremendous promise for treating a wide range of diseases and conditions. The cells come from early-stage embryos or, more commonly, from umbilical cord blood or our own bodies. Embryonic stem cells are considered the body's "master" cells because they can develop into any of our several hundred cell types. Adult stem cells, on the other hand, reside in mature tissues and organs like the brain, bone marrow, and skin, and their versatility is more limited. As an internal repair system for many tissue types, they replenish sick, injured, and worn-out cells.
Nowadays, with some sophisticated chemical coaxing, adult stem cells can be returned to an embryonic-like blank state, with the ability to become any cell type that the body might need.
Beauty product manufacturers convey in their advertising that the rejuvenating power of these cells could hold the key to the fountain of youth. But there's something the manufacturers don't always tell you: their products do not typically use human stem cells.
"The whole concept of stem cells is intriguing to the public," says Tamara Griffiths, a consultant dermatologist for the British Skin Foundation. "But what these products contain is plant stem cells and, more commonly, chemicals that have been derived from plant stem cells."
The plant stem cells are cultured in the lab with special media to get them to produce signaling proteins and peptides, like cytokines and chemokines. These have been shown to be good for reducing inflammation and promoting healthy cell functioning, even if derived from plants. However, according to Griffiths, there are so many active ingredients in these products that it's hard to say just what role each one of them plays. We do know that their ability to replenish human stem cells is extremely limited, and the effects of plant stem cells on human cells are unproven.
"...any cosmetic that is advertised to be anti-aging due to plant stem cells at this time is about as effective as all the skin creams without stem cells."
Whether products containing plant cell-derived ingredients work better than conventional skin products is unknown because these products are not regulated by the U.S. Food and Drug Administration and may rest on dubious, even more or less nonexistent, research. Cosmetics companies have conducted most of the research and the exact formulas they devise are considered proprietary information. They have no incentive to publish their research findings, and they don't have to meet standards imposed by the FDA unless they start using human cells in their products.
"There are biological limits to what you can do with plant cells in the first place," says Griffiths. "No plant stem cell is going to morph into a human skin cell no matter what magic medium you immerse it in. Nor is a plant cell likely to stimulate the production of human stem cells if applied to the skin."
According to Sarah Baucus, a cell biologist, for any type of stem cell to be of any use whatsoever, the cells must be alive. The processing needed to incorporate living cells into any type of cream or serum would inevitably kill them, rendering them useless. The splashy marketing of these products suggests that results may be drastic, but none of these creams is likely to produce the kind of rejuvenating effect that would be on par with a facelift or several other surgical or dermatological procedures.
"Plant stem cell therapy needs to move in the right direction to implement its inherent potential in skin care," researchers wrote in a 2017 paper in the journal Future Science OA. "This might happen in the next 20 years but any cosmetic that is advertised to be anti-aging due to plant stem cells at this time is about as effective as all the skin creams without stem cells."
From Beauty Counter to Doctor's Clinic
Where do you turn if you still want to harness the power of stem cells to reinvigorate the skin? Is there a legitimate treatment using human cells? The answer is possibly, but for that you have to switch from the Nordstrom cosmetics counter to a clinic with a lab, where plastic surgeons work with specialists who culture and manipulate living cells.
Plastic surgeons are experts in wound healing, a process in which stem cells play a prominent role. Doctors have long used the technique of taking fat from the body and injecting it into hollowed-out or depressed areas of the face to fill in injuries, correct wrinkles, and improve the face's curvature. Lipotransfer, or the harvesting of body fat and injecting it into the face, has been around for many years in traditional plastic surgery clinics. In recent years, some plastic surgeons have started to cull stem cells from fat. One procedure that does just that is called cell-assisted lipotransfer, or CAL.
In CAL, adipose tissue, or fat, is harvested by liposuction, usually from the lower abdomen. Fat contains stem cells that can differentiate into several cell types, including skin, muscle, cartilage, and bone. Fat tissue has an especially stem cell-rich layer. These cells are then mixed with some regular fat, making in effect a very stem cell-rich fat solution, right in the doctor's office. The process of manipulating the fat cells takes about 90 to 110 minutes, and then the solution is ready to be injected into the skin, to fill in the lips, the cheeks, and the nasolabial folds, or the deep folds around the nose and mouth.
Unlike regular fat, which is often injected into the face, some experts claim that the cell-enriched fat has better, longer-lasting results. The tissue graft grows its own blood vessels, an advantage that may lead to a more long-lasting graft – though the research is mixed, with some studies showing they do and other studies showing the complete opposite.
For almost all stem cell products on the market today in the U.S., it is not yet known whether they are safe or effective, despite how they are marketed.
One of the pioneers in CAL, a plastic surgeon in Brazil named Dr. Aris Sterodimas, says that the stem cells secrete growth factors that rejuvenate the skin -- like the plant stem cells that are used in topical creams and serums. Except that these cells are human stem cells and hence have inherently more potential in the human body.
Note that CAL doesn't actually result in large numbers of fresh, new replacement cells, as might be imagined. It's simply fat tissue treated to make it richer in stem cells, to have more of the growth-inducing proteins and peptides delivered to the dermis layer of the skin.
Sterodimas works alongside a tissue engineer to provide CAL in his clinic. He uses it as a way to rebuild soft tissues in people disfigured by accidents or diseases, or who are suffering the after-effects of radiation treatments for cancer.
Plastic surgeons get plenty of these patients. But how widespread is CAL for beauty purposes? Sterodimas says that he regularly performs the procedure for Brazilians, and it's widely available in Europe and Japan. In the U.S., the procedure hasn't taken off because there is no FDA approval for the various methods used by different doctors and clinics. A few major academic centers in the U.S. offer the treatment on a clinical trials basis and there are several trials ongoing.
But there is a downside to all lipotransfers: the transplanted fat will eventually be absorbed by the body. Even the cell-enriched fat has a limited lifespan before reabsorption. That means if you like the cosmetic results of CAL, you'll have to repeat the treatment about every two years to maintain the plumping, firming, and smoothing effects on the skin. The results of CAL are "superior to the results of laser treatments and other plastic surgery interventions, though the effect is not as dramatic as a facelift," says Sterodimas.
Buyer Beware
For almost all stem cell products on the market today in the U.S., it is not yet known whether they are safe or effective, despite how they are marketed. There are around 700 clinics in the U.S. offering stem cell treatments and up to 20,000 people have received these therapies. However, the only FDA-approved stem cell treatments use cells from bone marrow or cord blood to treat cancers of the blood and bone marrow. Safety concerns have prompted the FDA to announce increased oversight of stem cell clinics.
As for CAL, most of the clinical trials so far have been focused on using it for breast reconstruction after mastectomy, and results are mixed. Experts warn that the procedure has yet to be proven safe as well as effective. It's important to remember that this newborn science is in the early stages of research.
One question that has also not been definitively settled is whether the transplanted stem cells may give rise to tumors — a risk that is ever-present any time stem cells are used. More research is required to assess the long-term safety and effectiveness of these treatments.
Given the lack of uniform industry standards, one can easily end up at a clinic that overpromises what it can deliver.
In the journal Plastic Reconstruction Surgery in 2014, Adrian McArdle and a team of Stanford University plastic surgeons examined the common claims of CAL's "stem cell facelifts" being offered by clinics across the world. McArdle and his team write: "…the marketplace is characterized by direct-to-consumer corporate medicine strategies that are characterized by unsubstantiated, and sometimes fraudulent claims, that put our patients at risk." Given the lack of uniform industry standards, one can easily end up at a clinic that overpromises what it can deliver.
But according to McArdle, further research on CAL, including clinical trials, is proceeding apace. It's possible that as more research on the potential of stem cells accrues, many of the technical hurdles will be crossed.
If you decide to try CAL in a research or clinical setting, be forewarned. You will be taking part in a young science, with many unknown questions. However, the next time someone offers to sell you stem cells in a jar, you'll know what you're paying for.
Questions remain about new drug for hot flashes
In May, a new drug, Fezolinetant, was approved by the FDA to treat hot flashes associated with menopause.
Vascomotor symptoms (VMS) is the medical term for hot flashes associated with menopause. You are going to hear a lot more about it because a company has a new drug to sell. Here is what you need to know.
Menopause marks the end of a woman’s reproductive capacity. Normal hormonal production associated with that monthly cycle becomes erratic and finally ceases. For some women the transition can be relatively brief with only modest symptoms, while for others the body's “thermostat” in the brain is disrupted and they experience hot flashes and other symptoms that can disrupt daily activity. Lifestyle modification and drugs such as hormone therapy can provide some relief, but women at risk for cancer are advised not to use them and other women choose not to do so.
Fezolinetant, sold by Astellas Pharma Inc. under the product name Veozah™, was approved by the Food and Drug Administration (FDA) on May 12 to treat hot flashes associated with menopause. It is the first in a new class of drugs called neurokinin 3 receptor antagonists, which block specific neurons in the brain “thermostat” that trigger VMS. It does not appear to affect other symptoms of menopause. As with many drugs targeting a brain cell receptor, it must be taken continuously for a few days to build up a good therapeutic response, rather than working as a rescue product such as an asthma inhaler to immediately treat that condition.
Hot flashes vary greatly and naturally get better or resolve completely with time. That contributes to a placebo effect and makes it more difficult to judge the outcome of any intervention. Early this year, a meta analysis of 17 studies of drug trials for hot flashes found an unusually large placebo response in those types of studies; the placebo groups had an average of 5.44 fewer hot flashes and a 36 percent reduction in their severity.
In studies of fezolinetant, the drug recently approved by the FDA, the placebo benefit was strong and persistent. The drug group bested the placebo response to a statistically significant degree but, “If people have gone from 11 hot flashes a day to eight or seven in the placebo group and down to a couple fewer ones in the drug groups, how meaningful is that? Having six hot flashes a day is still pretty unpleasant,” says Diana Zuckerman, president of the National Center for Health Research (NCHR), a health oriented think tank.
“Is a reduction compared to placebo of 2-3 hot flashes per day, in a population of women experiencing 10-11 moderate to severe hot flashes daily, enough relief to be clinically meaningful?” Andrea LaCroix asked a commentary published in Nature Medicine. She is an epidemiologist at the University of California San Diego and a leader of the MsFlash network that has conducted a handful of NIH-funded studies on menopause.
Questions Remain
LaCroix and others have raised questions about how Astellas, the company that makes the new drug, handled missing data from patients who dropped out of the clinical trials. “The lack of detailed information about important parameters such as adherence and missing data raises concerns that the reported benefits of fezolinetant very likely overestimate those that will be observed in clinical practice," LaCroix wrote.
In response to this concern, Anna Criddle, director of global portfolio communications at Astellas, wrote in an email to Leaps.org: “…a full analysis of data, including adherence data and any impact of missing data, was submitted for assessment by [the FDA].”
The company ran the studies at more than 300 sites around the world. Curiously, none appear to have been at academic medical centers, which are known for higher quality research. Zuckerman says, "When somebody is paid to do a study, if they want to get paid to do another study by the same company, they will try to make sure that the results are the results that the company wants.”
Criddle said that Astellas picked the sites “that would allow us to reach a diverse population of women, including race and ethnicity.”
A trial of a lower dose of the drug was conducted in Asia. In March 2022, Astellas issued a press release saying it had failed to prove effectiveness. No further data has been released. Astellas still plans to submit the data, according to Criddle. Results from clinical trials funded by the U.S. goverment must be reported on clinicaltrials.gov within one year of the study's completion - a deadline that, in this case, has expired.
The measurement scale for hot flashes used in the studies, mild-moderate-severe, also came in for criticism. “It is really not good scale, there probably isn’t a broad enough range of things going on or descriptors,” says David Rind. He is chief medical officer of the Institute for Clinical and Economic Review (ICER), a nonprofit authority on new drugs. It conducted a thorough review and analysis of fezolinestant using then existing data gathered from conference abstracts, posters and presentations and included a public stakeholder meeting in December. A 252-page report was published in January, finding “considerable uncertainty about the comparative net health benefits of fezolinetant” versus hormone therapy.
Questions surrounding some of these issues might have been answered if the FDA had chosen to hold a public advisory committee meeting on fezolinetant, which it regularly does for first in class medicines. But the agency decided such a meeting was unnecessary.
Cost
There was little surprise when Astellas announced a list price for fezolinetant of $550 a month ($6000 annually) and a program of patient assistance to ease out of pocket expenses. The company had already incurred large expenses.
In 2017 Astellas purchased the company that originally developed fezolinetant for $534 million plus several hundred million in potential royalties. The drug company ran a "disease awareness” ad, Heat on the Street, hat aired during the Super Bowl in February, where 30 second ads cost about $7 million. Industry analysts have projected sales to be $1.9 billion by 2028.
ICER’s pre-approval evaluation said fezolinetant might "be considered cost-effective if priced around $2,000 annually. ... [It]will depend upon its price and whether it is considered an alternative to MHT [menopause hormone treatment] for all women or whether it will primarily be used by women who cannot or will not take MHT."
Criddle wrote that Astellas set the price based on the novelty of the science, the quality of evidence for the drug and its uniqueness compared to the rest of the market. She noted that an individual’s payment will depend on how much their insurance company decides to cover. “[W]e expect insurance coverage to increase over the course of the year and to achieve widespread coverage in the U.S. over time.”
Leaps.org wrote to and followed up with nine of the largest health insurers/providers asking basic questions about their coverage of fezolinetant. Only two responded. Jennifer Martin, the deputy chief consultant for pharmacy benefits management at the Department of Veterans Affairs, said the agency “covers all drugs from the date that they are launched.” Decisions on whether it will be included in the drug formulary and what if any copays might be required are under review.
“[Fezolinetant] will go through our standard P&T Committee [patient and treatment] review process in the next few months, including a review of available efficacy data, safety data, clinical practice guidelines, and comparison with other agents used for vasomotor symptoms of menopause," said Phil Blando, executive director of corporate communications for CVS Health.
Other insurers likely are going through a similar process to decide issues such as limiting coverage to women who are advised not to use hormones, how much copay will be required, and whether women will be required to first try other options or obtain approvals before getting a prescription.
Rind wants to see a few years of use before he prescribes fezolinetant broadly, and believes most doctors share his view. Nor will they be eager to fill out the additional paperwork required for women to participate in the Astellas patient assistance program, he added.
Safety
Astellas is marketing its drug by pointing out risks of hormone therapy, such as a recent paper in The BMJ, which noted that women who took hormones for even a short period of time had a 24 percent increased risk of dementia. While the percentage was scary, the combined number of women both on and off hormones who developed dementia was small. And it is unclear whether hormones are causing dementia or if more severe hot flashes are a marker for higher risk of developing dementia. This information is emerging only after 80 years of hundreds of millions of women using hormones.
In contrast, the label for fezolinetant prohibits “concomitant use with CYP1A2 inhibitors” and requires testing for liver and kidney function prior to initiating the drug and every three months thereafter. There is no human or animal data on use in a geriatric population, defined as 65 or older, a group that is likely to use the drug. Only a few thousand women have ever taken fezolinetant and most have used it for just a few months.
Options
A woman seeking relief from symptoms of menopause would like to see how fezolintant compares with other available treatment options. But Astellas did not conduct such a study and Andrea LaCroix says it is unlikely that anyone ever will.
ICER has come the closest, with a side-by-side analysis of evidence-based treatments and found that fezolinetant performed quite similarly and modestly as the others in providing relief from hot flashes. Some treatments also help with other symptoms of menopause, which fezolinetant does not.
There are many coping strategies that women can adopt to deal with hot flashes; one of the most common is dressing in layers (such as a sleeveless blouse with a sweater) that can be added or subtracted as conditions require. Avoiding caffeine, hot liquids, and spicy foods is another common strategy. “I stopped drinking hot caffeinated drinks…for several years, and you get out of the habit of drinking them,” says Zuckerman.
LaCroix curates those options at My Meno Plan, which includes a search function where you can enter your symptoms and identify which treatments might work best for you. It also links to published research papers. She says the goal is to empower women with information to make informed decisions about menopause.
A company in England has made a test that picks out the compounds from breath that reveal if people have liver disease.
Every year, around two million people worldwide die of liver disease. While some people inherit the disease, it’s most commonly caused by hepatitis, obesity and alcoholism. These underlying conditions kill liver cells, causing scar tissue to form until eventually the liver cannot function properly. Since 1979, deaths due to liver disease have increased by 400 percent.
The sooner the disease is detected, the more effective treatment can be. But once symptoms appear, the liver is already damaged. Around 50 percent of cases are diagnosed only after the disease has reached the final stages, when treatment is largely ineffective.
To address this problem, Owlstone Medical, a biotech company in England, has developed a breath test that can detect liver disease earlier than conventional approaches. Human breath contains volatile organic compounds (VOCs) that change in the first stages of liver disease. Owlstone’s breath test can reliably collect, store and detect VOCs, while picking out the specific compounds that reveal liver disease.
“There’s a need to screen more broadly for people with early-stage liver disease,” says Owlstone’s CEO Billy Boyle. “Equally important is having a test that's non-invasive, cost effective and can be deployed in a primary care setting.”
The standard tool for detection is a biopsy. It is invasive and expensive, making it impractical to use for people who aren't yet symptomatic. Meanwhile, blood tests are less invasive, but they can be inaccurate and can’t discriminate between different stages of the disease.
In the past, breath tests have not been widely used because of the difficulties of reliably collecting and storing breath. But Owlstone’s technology could help change that.
The team is testing patients in the early stages of advanced liver disease, or cirrhosis, to identify and detect these biomarkers. In an initial study, Owlstone’s breathalyzer was able to pick out patients who had early cirrhosis with 83 percent sensitivity.
Boyle’s work is personally motivated. His wife died of colorectal cancer after she was diagnosed with a progressed form of the disease. “That was a big impetus for me to see if this technology could work in early detection,” he says. “As a company, Owlstone is interested in early detection across a range of diseases because we think that's a way to save lives and a way to save costs.”
How it works
In the past, breath tests have not been widely used because of the difficulties of reliably collecting and storing breath. But Owlstone’s technology could help change that.
Study participants breathe into a mouthpiece attached to a breath sampler developed by Owlstone. It has cartridges are designed and optimized to collect gases. The sampler specifically targets VOCs, extracting them from atmospheric gases in breath, to ensure that even low levels of these compounds are captured.
The sampler can store compounds stably before they are assessed through a method called mass spectrometry, in which compounds are converted into charged atoms, before electromagnetic fields filter and identify even the tiniest amounts of charged atoms according to their weight and charge.
The top four compounds in our breath
In an initial study, Owlstone captured VOCs in breath to see which ones could help them tell the difference between people with and without liver disease. They tested the breath of 46 patients with liver disease - most of them in the earlier stages of cirrhosis - and 42 healthy people. Using this data, they were able to create a diagnostic model. Individually, compounds like 2-Pentanone and limonene performed well as markers for liver disease. Owlstone achieved even better performance by examining the levels of the top four compounds together, distinguishing between liver disease cases and controls with 95 percent accuracy.
“It was a good proof of principle since it looks like there are breath biomarkers that can discriminate between diseases,” Boyle says. “That was a bit of a stepping stone for us to say, taking those identified, let’s try and dose with specific concentrations of probes. It's part of building the evidence and steering the clinical trials to get to liver disease sensitivity.”
Sabine Szunerits, a professor of chemistry in Institute of Electronics at the University of Lille, sees the potential of Owlstone’s technology.
“Breath analysis is showing real promise as a clinical diagnostic tool,” says Szunerits, who has no ties with the company. “Owlstone Medical’s technology is extremely effective in collecting small volatile organic biomarkers in the breath. In combination with pattern recognition it can give an answer on liver disease severity. I see it as a very promising way to give patients novel chances to be cured.”
Improving the breath sampling process
Challenges remain. With more than one thousand VOCs found in the breath, it can be difficult to identify markers for liver disease that are consistent across many patients.
Julian Gardner is a professor of electrical engineering at Warwick University who researches electronic sensing devices. “Everyone’s breath has different levels of VOCs and different ones according to gender, diet, age etc,” Gardner says. “It is indeed very challenging to selectively detect the biomarkers in the breath for liver disease.”
So Owlstone is putting chemicals in the body that they know interact differently with patients with liver disease, and then using the breath sampler to measure these specific VOCs. The chemicals they administer are called Exogenous Volatile Organic Compound) probes, or EVOCs.
Most recently, they used limonene as an EVOC probe, testing 29 patients with early cirrhosis and 29 controls. They gave the limonene to subjects at specific doses to measure how its concentrations change in breath. The aim was to try and see what was happening in their livers.
“They are proposing to use drugs to enhance the signal as they are concerned about the sensitivity and selectivity of their method,” Gardner says. “The approach of EVOC probes is probably necessary as you can then eliminate the person-to-person variation that will be considerable in the soup of VOCs in our breath.”
Through these probes, Owlstone could identify patients with liver disease with 83 percent sensitivity. By targeting what they knew was a disease mechanism, they were able to amplify the signal. The company is starting a larger clinical trial, and the plan is to eventually use a panel of EVOC probes to make sure they can see diverging VOCs more clearly.
“I think the approach of using probes to amplify the VOC signal will ultimately increase the specificity of any VOC breath tests, and improve their practical usability,” says Roger Yazbek, who leads the South Australian Breath Analysis Research (SABAR) laboratory in Flinders University. “Whilst the findings are interesting, it still is only a small cohort of patients in one location.”
The future of breath diagnosis
Owlstone wants to partner with pharmaceutical companies looking to learn if their drugs have an effect on liver disease. They’ve also developed a microchip, a miniaturized version of mass spectrometry instruments, that can be used with the breathalyzer. It is less sensitive but will enable faster detection.
Boyle says the company's mission is for their tests to save 100,000 lives. "There are lots of risks and lots of challenges. I think there's an opportunity to really establish breath as a new diagnostic class.”