Author Archives: Dr. Greg Maguire, Ph.D.

Atopic Dermatitis, Bugs, and Itching

The skin barrier in the epidermis is constantly exposed to microbes and their products. The role of microbes in itch generation was previously unstudied. Deng et al (2023) find that Staphylococcus aureus, a bacterial pathogen associated with itchy skin diseases, directly activates pruriceptor sensory neurons to drive itch.

When the scientists injected MRSA, a type of S. aureus, under the skin of mice, as expected, the mice itched so much that they damaged their skin. But the authors claim to have measured no inflammation associated with the injection. This provides evidence that inflammation is not required for itch to occur.

Instead, research has found that when S. aureus invades the skin, it releases 10 different enzymes, or proteases. One of them, called V8, binds to a protein on nerve cells called proteinase-activated receptor 1, or PAR1. Activation of PAR1 likely starts a chain reaction from the skin neurons, to the spinal cord, and to the brain, which then triggers the urge to itch. In the mouse model used by Deng et al, the itching stopped when researchers used Vorapaxar, a drug that blocks the PAR1 receptor. This may not be the only mechanism by which itching occurs, but this is an important new discovery and gives us much insight into the some of the mechanisms underlying pruritis.

From Deng et al (2023)

As Ogonowska et al (2023) have described, Staphylococcus aureus massively colonizes the skin of patients with atopic dermatitis (AD), and the frequency of detection of multidrug-resistant S. aureus (MRSA) in AD patients is higher than the healthy population, which makes treatment much more difficult. 

There’s hope though, and that hope involves using simple, topically applied symbiotic bacteria that are safe and natural to the skin. One set of bacteria are the nitrifying bacteria (Nitrosomonas, Nitrospira, and Nitrobacter), used in NeoGenesis MB-1. The MB-1 product has been on the market since 2015 and is multifunctional – benefiting a number of skin conditions, including acne. As one mechanism of action, Maguire and McGee (2023) hypothesize the MB-1 acts to destroy pro-inflammatory bacteriophage (viruses) associated with acne through a natural CRISPR mechanism in the probiotic bacteria.

These type of nitrifying bacteria in MB-1 have also been found to reduce pruritis and inflammation in humans with atopic dermatitis. Additionally, NeoGenesis is currently testing our second probiotic product that incorporates Bacillus subtilis and Lactobacilli. The bacterium B. subtilis has been found to reduce the S. aureus when topically applied, and Lactobacilli have been found to do the same while reducing the symptoms of AD.

NeoGenesis will have two probiotic products that will be used together in a topical application to renormalize the skin’s microbiome in AD, reduce pruritis, and restore barrier function. Stay tuned.

Reducing Sodium Intake Not Only Reduces Blood Pressure, Skin Inflammation is Reduced

In a recent trial (Gupta et al, 2023), the blood pressure–lowering effect of dietary sodium reduction was comparable with a commonly used first-line antihypertensive medication. Salt in the diet is associated with chronic kidney disease. Sodium also accumulates in the skin, inducing inflammation and eczema, so feel better and look better by cutting the sodium intake that is way too high in most people.

I discuss at length in my book, Thinking and Eating For Two: The Science of Using Systems 1 and 2 Thinking to Nourish Self and Symbionts, how diet is key to all chronic diseases. All of the dietary components work together to largely determine health status – not just one and certainly not just genetic factors. Genetics has little to do with health status for most people. Hereditary factors, such as epigenetic transgenerational inheritance and protein inheritance, may have an important influence, but not genetics. It’s the exposome that counts – i.e. all of the things that you’re exposed to in life – and, all of the things that you’re parents and their parents were exposed to. That’s the transgenerational epigenetic inheritance and protein inheritance aspect of the exposome. Now research at the University of California, San Francisco (UCSF) and UC Berkeley, suggests that high levels of dietary sodium may raise the risk of developing atopic dermatitis.

Many factors can influence health, including that of the skin. I’ll discuss salt here, but other factors such as dairy play a big role too – both for cardiovascular health, and skin health. For example, the induction of antibodies (IgE) by the consumption of dairy can lead to cardiovascular disease and death. And dairy, loaded with antigens such as lactose, whey, and casein (even found in mothers milk because of dairy consumption by mom) can be destructive to the skin, even causing cancer.

As Gupta et al (2023) discovered, dietary sodium reduction significantly lowered blood pressure (BP) in the majority of middle-aged to elderly adults they studied. The decline in BP of those who went from a high- to low-sodium diet was independent of hypertension status and antihypertensive medication use, and was consistent across subgroups. Needless to say, reducing sodium intake did not result in adverse events.

Sodium is an essential mineral and osmolyte for the human body. It is the major cation in the extracellular fluid and as such plays a crucial role in homeostatic processes such as regulation of blood volume, osmolarity, and blood pressure. Therefore, sodium plasma concentration is maintained within a relatively narrow range of around 140 mmol/l. The sodium concentration in the interstitial space (the space in between our cells) can be much higher. We consume just the right amount of sodium when we eat a plant based diet without added sodium. If we eat too much sodium, that excessive salt intake may induce several adverse effects, causing microvascular endothelial inflammation, anatomical remodeling, and functional abnormalities, even in normotensive subjects (those with normal blood pressure). More recent studies have shown that changes in sodium plasma levels not only exert their effects on small resistance arteries, but may also affect the function and structure of large elastic arteries. The issue of salt-sensitivity, which refers to individual susceptibility in terms of BP variations following changes in dietary salt intake, has also been recently debated in its pathophysiological mechanisms and clinical implications.

Excess sodium is also stored in the skin.  In the skin microenvironment, higher sodium concentrations enhance macrophage function, potentially leading to innate immune system-based inflammation. Several studies have provided significant evidence that an elevated sodium concentration has an immunomodulating effect by augmenting proinflammatory and antimicrobial macrophage function as well as T-cell activation. And now we know that sodium has accumulated to high levels in the skin of psoriasis patients (Maifeld et al, 2021). Psoriasis is an inflammatory skin condition, and restricting salt in your diet will help to reduce that inflammation. Same for eczema. Reduce the salt because, for one factor, salt promotes the growth of a bad bacteria called staph aureus which is found in patients who have bad flare ups of eczema. With high salt, the skin is unable to repair itself – it’s in a constant state of inflammation.

Cut the salt and your immune system will operate more normally. It requires time to adjust your taste to the low sodium diet – most of us are addicted to salt. But in time, you lose the addiction, and actually begin to better taste all of the other flavors in your food that were masked by the salt. Bon appetite, Pas de sel!

Stem Cell Aging and Loss of Tissue Maintenance Because of Inflammaging

Early and mid-life inflammation ia a mediator of lifelong defects in tissue maintenance and regeneration due to the inflammation aging the stem cells. Inflammation damages the extracellular matrix, DNA, and epigenetic mechanisms, all of which contribute to aging and age-related diseases.

A schematic of stem cell inflammaging (from Bogeska et al, 2022)

Inflammaging, defined as an age-related increase in the levels of pro-inflammatory markers in blood and tissues, is a strong risk factor for multiple diseases that are highly prevalent, and frequent causes of disabilities in elderly individuals but are pathophysiologically uncorrelated, i.e., everything from cancer, to skin diseases, to heart disease, and neurodegeneration. And remember, as I’ve discussed in previous blogs, inflammation in the skin can can lead to systemic inflammation.

Inflammation can wreak havoc on the body, including the skin, through a number of key mechanisms. Let’s have a look at how inflammation can damage tissue, such as by degrading the extracellular matrix, and can damage cells at the molecular level through genetic and epigenetic mechanisms. Genetic refers to how damage occurs to the DNA, and epigenetic refers to how damage occurs “above” the DNA, such as the mechanisms that control the expression of DNA – i.e., affecting how the DNA makes RNA and proteins. Inflammation can also cause misfolding in proteins, resulting in a number of dysfunctional pathways in the body, including the control of epigenetics such as protein-based epigenetics. You read that right – proteins can be inherited and dysfunctional proteins in an adult can be inherited as dysfunctional proteins in the offspring. That’s one reason why genetics and heredity don’t mean the same thing.

Inflammaging is a process induced by chronic inflammatory cytokine signaling that promotes accelerated damage to the extracellular matrix (ECM), stem-cell aging, and precancer stem-cell generation. Multiple different sterile and infection-associated inflammatory stimuli have been shown to provoke primitive stem cells (HSCs) to exit their long-term quiescent state and enter into active proliferation. In other words, inflammation, whether it is sterile inflammation or infection-related inflammation, drives stem cells into a state where they multiply. Therefore, chronic inflammation will induce the constant multiplication of stem cells. And every time a cell multiplies itself, mutations and consequent aging processes will occur. As I’ve said before, one of the most dangerous things a cell can do is to multiply itself. 

As scientists have recently published, their work demonstrates that inflammatory stimuli can provoke a long-lasting inhibitory effect on tissue regeneration that extends far beyond the duration of the original inflammatory event, via the progressive and irreversible attrition of the functional stem cell pool. They argue that prophylactic anti-inflammatory interventions may effectively delay or prevent the evolution of age-associated pathologies, but that such treatments may hold limited capacity to rejuvenate an already aged stem cell system. 

In other words, it is important to reduce inflammation even during our younger years, not just during our aged period, in order to reduce stem cell aging processes. This means eating a plant-forward diet, full of lots of fruits and vegetables, as well as using sunscreen during long sun exposures, as well as using skin products that are not inflammatory – rather using skin care products that reduce inflammation and those that help to maintain or build the skin’s barrier function.

Suboptimal Exosome Product Brought to Market By Failed Company – Benev, and Another Local Company – Invitrx

Failed company brings suboptimal skincare product to market by a manufacturer in Korea, known for fraudulent and corrupt stem cell science, even at it’s premier university, Seoul National University.

Benev is a company that couldn’t survive in the market, and had numerous problems as exemplified by this FDA review where they found poor quality control and the use of expired materials being used in production:

http://fda-warning-letters.blogspot.com/2010/06/benev-company-inc.html

For example, Benev was using expired ingredients to manufacture drugs that went to market, and falsified documents to hide their egregious behavior (below is from a FDA Warning Letter to Benev):

“QCD” refers to Benev’s quality control department.

As a consequence of this violation, and may other violations, FDA concluded that Benev’s drug products were adulterated:

Resulting from continued poor performance, Benev sold themselves to a Korean company, ExoCoBio, that uses Benev to sell exosomes in the USA. A culture of corruption and fraud was highlighted by the veterinarian, Hwang Woo-suk, and his many conspirators who faked a landmark stem cell publication. That culture was exported to the USA by Benev. Previously, Benev worked with another local company called Invitrx, a company with a rich history of FDA violations, a long history, and led by a man, Habib Torfi, known for delivering stem cells to patients in a grocery bag.

There are numerous problems with what Benev (ExoCoBio) is doing to exosomes.

First, exosomes are only a fraction of what stem cells release, and without the non-exosomal fraction being combined with the exosomes, suboptimal results are achieved. In other words, when the exosomes aren’t isolated but are combined with the soluble fraction as is natural when the stem cells release their molecules, the results are superior to using only the isolated exosomes.

Second, they lyophilize their exosomes – this is a freeze-drying process that damages the molecules inside the exosome, and molecules attached to the outside of the exosome. Basically this harsh process removes all the water from the product, leaving a small amount of dry powder. The powder is full of damaged proteins and other molecules. Lyophilization leads to aggregation of proteins and their denaturization. “Unfortunately, the lyophilization process generates both freezing and drying stresses, which can denature proteins to various degrees” (Wang, 2000). Protein denaturation refers to the loss of biological activity through changes of the specific spatial conformation of protein in certain physical or chemical factors, resulting in the change of physical and chemical properties.

Lyophilization is used for the convenience of the company – it’s easier to store and ship a small pellet of lyophilized powder than it is to store and ship fresh, undamaged exosomes contained in their original solution.

From the Benev website we see they’re using lyophilized exosomes, and only the exosomes without the benefit of the soluble fraction (the overlapping text on their website is another example of the lack of attention to detail in this failed company):

To compare, NeoGenesis uses fresh (not damaged from freeze-drying) S2RM that contains both the 1. exosomal fraction, and 2. soluble fraction. Also, NeoGenesis uses both fractions from 3 cell types derived from the skin (mesenchymal stem cells and two types of fibroblasts). In contrast, Benev uses only a portion of the molecules released from one cell type, yielding a much depleted set of molecule types compared to NeoGenesis, many of which are damaged by Benev using  lyophilization. 

Another nearby company, Invitrx, in Lake Forest, is selling non-sterile exosomes for injection – allogenic injection. Talk about dangerous. Invitrx has a long history of unsafe practices. For example, illegally selling stem cells for injection, delivered in a paper grocery bag and selling non-sterile exosomes to physicians as exemplified in this FDA 486 Warning Letter, in which the agency details numerous non-sterile practices used to produce their exosomes.

You can read about the problems with lyophilization with many references to the published literature in my blog:

Why NeoGenesis Doesn’t Lyophyilize (Freeze Dry) Our Secretome/Exosome S2RM – Fresh is Better

Chirality Gobbledygook in the Popular Press and from Company (dis)Info

Please stop using D- and L- because it shows your profound ignorance. And, yes, both R- and S-Mandelic Acid work in the body. And, please don’t use mandelic acid with only one enantiomer as some companies want you to – it’s toxic! And please don’t drink your sunscreen – it’s stupid!

Organic compounds, molecules created around a chain of carbon atom, commonly known as carbon backbone, play an essential role in the chemistry of life. The carbon atom is unique among elements in its tendency to form extensive networks of covalent bonds not only with other elements but also with itself. Because of its position midway in the second horizontal row of the periodic table, carbon is neither an electropositive nor an electronegative element; it therefore is more likely to share electrons than to gain or lose them. In other words, it’s stable and doesn’t require the gain or loss of electrons, yet permissive because it has 4 electrons to share. Of all the elements in the second row, carbon has the maximum number of outer shell electrons (four) capable of forming covalent bonds. Other elements, such as phosphorus [P] and cobalt [Co], are able to form five and six covalent bonds, respectively, with other elements, but they lack carbon’s ability to bond indefinitely with itself. As such, carbon can form an extensive number of molecules types, and indeed, very complex molecules. These molecules are important in the energy they carry, mainly in a form of potential energy between atomic molecules. Since such potential force can be widely affected due to changes in atomic placement, it is important to understand the concept of an isomer, a molecule sharing same atomic constituents as another but differing in structural arrangement.

Stereoisomers are isomers that differ in spatial arrangement of atoms, rather than order of atomic connectivity. One type of isomer is the mirror-image stereoisomers, a non-superimposable set of two molecules that are mirror image of one another. The existence of these molecules are characterized by a concept known as chirality.

D and L configuration is an old classification that is rarely used by scientists, but is commonly used by dilletantes in the popular press and cosmetic companies who are clueless about chemistry, especially stereochemistry. D- and L- as incorrectly used by dilletantes is said to have been used to point out optical rotation in the early days that preceded a knowledge of stereochemistry. Unbeknownst to the dilletantes is that optical rotation is indicated by lowercase “d” and “l”, not uppercase. The modern way of describing chirality of molecules is the R-S system. If you want to understand how chirality is determined using the R,S system, here’s a simple guide, and a summary diagram is given below.

How did D and L originate, and why the confusion? D and L were originally used by Prof. Dr. Emil Fischer, Ph.D., in about 1891, when he was busy determining the configurations of all the sugars (glucose) by building them from d-glyceraldehyde, which has one chiral center. Chiral centers were already known to exist, although scientists were not able to determine their absolute configuration until about 1951. The idea of the chiral center was developed by a Dutch chemist, Prof. Dr. Jacobus Henricus van ‘t Hoff, Ph.D.,  in 1874, the first scientist to be awarded the Nobel prize in chemistry.

Prof. Dr. Emil Fischer, Ph.D., working in Germany, decided that d-glyceraldehyde was what we would now call “R”. Since his method of building sugars from D-glyceraldehyde preserved the original chiral center, he was able to determine that all the sugars he built also had D configuration in their last chiral center; that’s why we talk of “D-sugars.” In other words, building from a D-sugar led to the building of other D-sugars. Big D and Little D simply referred to sugars built from d-glyceraldehyde.

Back in the day when I lectured students about biochemistry, I would introduce D and L as a historical fact that they will have to deal with because of misinformation by non-chemists in the medical literature. Let’s review:

We now use a different system that is absolute in determining the chirality of molecules, and it uses R and S. Here’s a summary:

While the chiral (R)-mandelic acid (R-MA) is important for the drug industry because it’s a useful chiral building block for the synthesis of aromatic drugs, it is of crucial importance in the chemical and pharmaceutical industry. In humans, S-mandelic acid undergoes rapid chiral inversion to R-mandelic acid. So a racemic mixture of the R- and S- enantiomers is of little importance when using mandelic acid for topical skin applications, even if the R- and S- were shown to have different effects – and they haven’t been found to have different effects. Chiral chemicals often have functionality in both enantiomers, often with the function of each enantiomer acting at different pathways. The function of R- versus S- for many chemicals, including drugs, has not been determined.

Possible Toxicity of Using Mandelic Acid With Only One Steroisomer (enantiomer)

Here’s why you don’t want to use pure R-mandelic acid. (R)–MA is mainly synthesized chemically. The cyanide-based method involved two-step reactions including cyanation of benzaldehyde using either NaCN or transition metal catalysts, such as titanium or vanadium complexes of chiral ligands, followed by the hydrolysis of mandelonitrile using HCl to give enantiopure (R)–MA (Blacker and Houson 2002; Corson et al. 2003). This method requires the use of highly toxic cyanide and expensive transition metal catalyst together with chiral ligands but gives unsatisfied ee (meaning it doesn’t yield enantiomer excess, i.e. it doesn’t yield just the R- enantiomer), low overall yields, and generates a lot of by-products and large amount of waste. The dichloroacetophenone-based method involved the chlorination of acetophenone with chlorine, followed by alkaline hydrolysis by NaOH at 65 °C and the acidolysis with HCl. This method requires the use of toxic and dangerous Cl2, high temperature, and also suffers from side products problems (mono, tri-choloroacetophenone) (Aston et al. 2003).

Bottom line, and practically speaking, chemical methods are mainly used to produce racemic Mandelic Acid (not chiral Mandelic Acid) because it works, it’s clean (not toxic), it’s inexpensive, and it’s sustainable. It makes sense.

BareFacedTruth.com is a Blog from a Physician Who Lost His Medical License

Having committed malpractice and losing his medical license, John Sanderson started a company called AnteAge, selling potentially dangerous products to unsuspecting victims. Negligence, repeated negligence, and sexual misconduct with his patients was his contribution to medicine. Now he wants to sell you products for your skin. He also has someone write a blog for him that not only demonstrates his total incompetence yet again, but he projects on others what he does daily – namely lie and commit unethical acts.

Reference: https://www2.mbc.ca.gov/BreezePDL/document.aspx?path=%5cENF0003%5c16%5c&did=FSMB53N0.DID

Mr. Sanderson is a physician who attained a bachelor’s degree in medicine from Canada. This program is 5 years in college total, and the curriculum apparently doesn’t teach ethics or compassion for others.

John Sanderson, M.B.B.S. (bachelor’s degree in medicine) who lost his medical license for negligence and repeated negligence, and sexual misconduct with a female patient.

If you want to read about Mr. Sanderson’s exploits as a practicing physician, look him up here.

I’ve selected a few excerpts shown below:

Sanderson previously was a family practice physician with an undergraduate medical degree – a bachelor’s degree in medicine. Once Sanderson finished his Canadian undergraduate degree in medicine, and once he passed the medical board test in the US, regulations permitted him to use the designation “M.D.” Sanderson frequently finds himself in disputes with other companies, one of which apparently exposed that Sanderson committed domestic violence.

Sanderson was not trained as a dermatologist and was not board certified. He obviously has little to no understanding of the skin’s powerful immune system, and no idea of how bone marrow mesenchymal stem cells work in the body. Upon losing his medical license, he started a company to do further harm to people by having them use products that induce inflammation and potentially cancer. The other physicians who is part of AnteAge and the co-blogger with Mr. Sanderson, is George Taylor, a retired anesthesiologist. Like Sanderson, Taylor has no science background and no published scientific papers. So ignorant is this guy that he has a video saying that red blood cells have no signaling capacity. That they don’t have or react to cytokines. Sorry, George. They do. I’d hate to have this sleepy guy putting me to sleep on the operating table.

Trying to understand why a company would bring a proinflammatory, possibly pro-oncogenic product to the market, I looked closer at the company. Because John Sanderson is not a scientist, and has never listed that he has any scientific publication, only misleading blogs, I wondered how did he come to choose his technology. I discovered that Sanderson had enlisted fellow Canadian, Jonathan Lakey, Ph.D. as his scientific advisor. To no surprise, the man who had lost his medical license because of incompetence had hired a scientist, Jonathan Lakey, who had been fired from his university because of fraud.

A non-profit government organization in Canada fired Jonathan Lakey for the same reason:

Then Jonathan Lakey was charged with fraud and racketeering at one of the companies in which he was an officer:

Jonathan Lakey’s involvement with a number of other companies that are pump and dump schemes has made the news a number of times. Clearly, using a product on your skin from this dynamic fraudster-incompetence duo is a bad choice – they do not have anyone’s well being in mind.

There are other skin care companies led by physicians. I suggest if you’re interested in their products, go to the state medical board website in which they practice, and look at the current status of their medical license. For example, you can search physicians in California here, and in Colorado here. You may be surprised what you find. Simply type in their name, and you’re likely to find disiplinery actions and loss of license.

Eczema (Atopic Dermatitis): Delayed Gut Microbiota Maturation in the First Year of Life is a Hallmark of Pediatric Allergic Disease

Allergic diseases affect millions of people worldwide, and are on the rise. An increase in the prevalence of these diseases has been associated with alterations in the gut microbiome, i.e., the microorganisms within the gastrointestinal tract. Maturation of the infant immune system and gut microbiota occur in parallel; thus, the normal development of the microbiome likely determines tolerant immune programming in the infant. Antigens are substances that can produce an immune response, and tolerant immune programming is a mechanism of immune tolerance where the self-antigen is protected from the immune system’s destructive response. Thus the immune system is programmed to be destructive against non-self-antigens (bacteria and viruses contain non-delf antigens, for example), but not self antigens. 

A new study reported that a trend in maturation alteration is characterized by depletions in the bacterial species A. hadrus, F. saccharivorans, E. hallii, and B. wexlerae in participants who later developed allergic diseases, as well as enrichments in E. lenta, C. innocuum, E. faecalis, E. coli, and T. nexilis in these participants. The depleted bacterial populations are known short-chain fatty acid (SCFA) producers, notably the butyrate producers A. hadrus, E. hallii, and F. saccharivorans and the acetate producer B. wexlerae; SCFAs are metabolites that mediate well-defined host benefits within the gut. The authors also reported a depletion of butyrate in allergy-prone participants and significant associations between A. hadrus and F. saccharivorans respective relative abundance and butyrate concentration. This strengthens the postulation that the production of butyrate and its effect on immune cells is a mode by which optimal immune modulation occurs during early life. In contrast, species enriched in allergy-prone participants have been linked to pathogenic activity and poor health outcomes, with many of these microbiome features associating with metabolites enriched within these same participants.

Most diseases are consequence of our exposome, and not hereditary genetic factors. Our exposome greatly affects our microbiome. Established primarily during infancy, the developing microbiota’s initial expansion and fluctuation are particularly sensitive to external influences before reaching a more stable community. Sensitivity of the microbiome is most pronounced during infancy, and abnormal exposures, such as that in a hospital setting, especially during a C-section, that can drastically alter the microbiome. The number of C-Sections in 2015 doubled in comparison to those registered in 2000, and jurisdictions such as California have instituted programs to stop the medical practice of performing unneeded C-sections. Indeed, many risk factors for allergic diseases, including mode of delivery, diet, urban living, and antibiotic exposure (such as the overprescribed broad spectrum antibiotic Amoxicillin), also influence early microbiota membership and structure. Note: the broad spectrum antibiotics are particularly harmful because the drug kills so many beneficial types of bacteria. While this maturation process usually coincides with the development of healthy immune tolerance, allergic sensitization can emerge in many children because of their exposome during the same period as the microbiota is being established.

Overall, the authors compared 1115 children with asthma, allergic rhinitis, food allergy, or Eczema (atopic dermatitis) to a rigorously defined, non-allergic comparator group. They described detailed underpinnings driving this decrease in gut microbiome maturation, encompassed within the alteration of a core group of bacterial species, functional pathways (i.e., potential intestinal mucous integrity breakdown, elevated oxidative stress levels, and subsequently oxidized monosaccharides, and diminished secondary fermentation), and metabolic imbalance i.e., elevated trace amines that can be involved in inflammation and neural function, and associated with reduced microbiota-maturation age and elevated risk of allergy.

Bottom line, the infant exposome is critical for the development of a normal microbiome and a life without allergy and skin conditions without Eczema.

Finally, Some Good Genetics Research on Aging Processes – Implications for the Skin

Professor Doctor Andreas Beyer, Ph.D., at the University of Cologne, Institute for Genetics in Germany, along with his research team has discovered that as we age, a critical process in our cells, called gene transcription, speeds up. This process involves making a copy of a specific DNA strand into the form of RNA. When the process occurs too fast, more errors are made. The RNA is then used for a number of things, including making the backbone of proteins. Posttranslational modifications then finish the making of proteins. If the protein’s backbone is error ridden, the protein loses function. Likewise, posttranslational modification (PTM) depends on other proteins, and if they are error ridden, then error ridden PTM will also lead to dysfunctional proteins.

What does this mean for our health? Dr. Beyer says, for example, “Our study is saying that, for instance, having a healthy diet or, this caloric restriction intervention, would improve the quality of the transcription of the RNA production in the cell. And this would then have beneficial effects for the cells in the long run.” The evidence for his statement; mice and worms following a low-calorie diet were assessed to gauge the impact on cell transcription during the aging process. In both scenarios, transcription’s pace was observed to be more measured, resulting in fewer errors.

To validate their experiment’s applicability to humans, they conducted assessments using blood samples from both young and elderly humans. Prof. Dr. Argyris Papantonis, Ph.D., at the University of Gottingen in Germany, one of the principal investigators, remarked, “And when we compared the young cells to the very old cells, in vitro, we got exactly the same results.”

Skin aging is characterized by the accumulation of macromolecular and molecular damage within cells, impaired ability of stem and progenitor cells to promote tissue regeneration, and restore the loss of normal physiology. Chronological aging and photo-aging are two processes of skin aging that although related, have different clinical manifestations and pathogenesis. Chronological aging appears as we age and is affected by factors such as ethnicity, individual epigenetics and exposome, and skin site. It is mainly characterized by dry skin, dullness, lack of elasticity, sagging, discoloration, and fine wrinkles. Histological features include epidermal atrophy, reduction in the number of dermal fibroblasts and collagen fibers, slackening, thinness, and functional disorganization of the cells and matrix. The primary causes are: first, the stem cell dysfunction of keratinocytes, decreased regenerative ability of stem cells in the basal layer of the epidermis leading to a decline in skin renewal and repair ability, ultimately causing aging, and second, due to the accumulation of damage and aging skin dysfunction, fibroblasts lose the ability to reshape the extracellular matrix or have a reduced ability to synthesize and secrete collagen or viscous proteins. Third, aging fibroblasts alter intracellular homeostasis through certain paracrine mechanisms Now we know an important basis for these aging associated deficits is an increase in the speed of making transcripts (RNA made from DNA), and the resulting dysfunction of proteins.

As I have written, proteins being affected by our exposome is the largest factor in diseases, including cancer. A big portion of your exposome is diet. So eat well and ignore David Sinclair, your processing of transcripts in the skin will be renormalized..

Carotenoids and Skin Health

Eat your vegetables, because only they can provide all the carotenoids needed by the body for many functions, including anti-cancer effects in the skin.

Carotenoids are yellow, orange, and red organic pigments produced by plants, bacteria, and algae. These pigments are important to human health, including the health of the skin, and must be acquired by diet. Carotenoids can also be fed to the skin topically. The outer layer of the skin is rich in carotenoids, and evidence finds that the sebum and perspiration naturally feed carotenoids to the epidermis. So well formulated topical products can feed the skin carotenoids too.

There are over 1,100 known carotenoids, which can be further categorized into two classes, xanthophylls (which contain oxygen) and carotenes (which are purely hydrocarbons and contain no oxygen). All are produced from 8 isoprene molecules and contain a backbone of 40 carbon atoms. The conjugated carbon chains of carotenoids quench singlet oxygen and other radical species. Carotenoids have antioxidant and anti-inflammatory effects in our tissues. The antioxidant and anti-inflammatory effects of carotenoids have been found to aid in the prevention of a wide range of oxidative disorders, including arteriosclerosis, obesity, and various types of cancers.  In general, carotenoids absorb light wavelengths ranging from 400 to 550 nanometers (violet to green light). This causes the compounds to be deeply colored yellow, orange, or red because the violet to green colored light has been absorbed by the pigment, leaving the longer, yellow to red wavelengths of light to be seen by our eyes. In autumn, when there are fewer daylight hours and temperatures are cooler, photosynthesis slows down and there is less chlorophyll production in plants. The reduction of chlorophyll reveals yellow and orange carotenoid pigments that are usually hidden by the abundance of chlorophyll present in leaves during the growing season. Carotenoids are the dominant pigment in autumn leaf coloration of about 15-30% of tree species. Certain carotenoids that contain unsubstituted beta-ionone rings (including β-carotene, α-carotene, β-cryptoxanthin, and γ-carotene) have vitamin A activity, meaning these carotenoids can be converted to retinol in our skin.

From Tan et al (2019), molecular structures of carotenes (Phytoene, lycopene, γ-carotene, α-carotene, β-carotene, and δ-carotene).

And, molecular structures of some common xanthophylls (β-cryptoxanthin, zeaxanthin, lutein, astaxanthin, and fucoxanthin).

Human skin, is relatively enriched in lycopene and β-carotene types of carotenoids, compared with lutein and zeaxanthin. Dietary lutein and zeaxanthin are selectively taken up into the macula (central area of our retina where high contrast imaging occurs) of the eye, where they absorb up to 90% of blue light and help maintain optimal visual function. Unlike the other carotenoids, they are not precursors to retinol. Carotenoids are important components of the dark brown pigment melanin, which is found in hair, skin, and eyes. Melanin absorbs high-energy light and protects the skin from intracellular damage. β-carotene is an endogenous photoprotector, and its efficacy to prevent UV-induced erythema formation has been found in a number of studies. In the human skin, the highest concentration of carotenoids is found within adipocytes in the fat-rich subcutaneous tissue and in the stratum corneum (SC) within the lipid lamellae. The carotenoid concentration is not homogeneously distributed in the SC and has two maxima, occurring near the surface and near the bottom of the SC, which is explained by the two independent delivery pathways: from the inside due to blood circulation and keratinization, and from the outside with sweat and/or sebum secretion. Topical retinoid treatments inhibit the UV-induced, MMP-mediated breakdown of collagen and protect against UV-induced decreases in procollagen expression. Preclinical data indicate that carotenoids exhibit direct antimelanoma effect, and inhibit cell proliferation, cell migration and invasion in various melanoma cell lines grown in the lab. In a clinical study, topical carotenoids significantly enhanced skin hydration and elasticity, and reduced erythema, melanin and sebum contents over a 12 week treatment period. Several studies have observed positive effects of high-carotenoid diets on the texture, clarity, color, strength, and elasticity of skin. Beta-carotene supplementation altered skin color to increase facial attractiveness and perceived health in humans.

Let’s go a little deeper into the science when we consider our exposure to sunlight. UV radiation from the sun causes the production of free radicals in our skin. Free radicals can be particles, atoms, or molecules that have one or more unpaired electrons on the outer valence shell. This condition changes the chemistry of the molecules in our skin making them chemically very reactive. The free radical molecules try to regain their missing electron by obtaining it from the surrounding molecules. If the electron is obtained, the “stolen” electron leaves the donor molecule in a damaged state. Most free radicals contain oxygen, so they are called reactive oxygen species (ROS). The most common ROS in the biological tissues are superoxide anion radicals (O2•−), hydroxyl radicals (•OH), hydrogen peroxide (H2O2), and singlet oxygen (1O2). Also occurring are reactive nitrogen species (RNS) and lipid oxygen species (LOS) can be developed, such as lipoperoxynitrite radicals (LOO•), causing lipid peroxidation reaction cascades, inflammatory responses, and DNA and protein damage. Oxidized lipids, similar to old, rancid cooking oils that you’ve been warned not to use, can be toxic and act as lipid radicals or oxidants. The interaction of the ROS hydrogen peroxide with iron (Fenton reaction) causes chronic inflammation, sometimes leading to Ferroptosis, a form of programmed cell death. The interaction of ROS and RNS with biological molecules and cells may cause irreversible damage to their structure, which may lead to cellular dysfunction. Most of the oxygen we breath and that is consumed by cellular mitochondria in the multistep processes of oxidative phosphorylation is converted into water, while a small fraction can diffuse out of the respiratory chain as ROS and RNS. ROS and RNS are able to permeate the skin, including the stratum corneum (SC). Plasma medical procedures that damage the skin depend on this mechanism. Therefore, whether the damage is intentional, such as a medical procedure, or unintentional, such as too much exposure to the sun, carotenoids are a critical part of better preventing and remediating such damage through their antioxidant effects.

The human body, including the skin, contains a balanced set of antioxidants that can be divided into two main classes—endogenous and exogenous antioxidants. The major enzymatic endogenous antioxidants include glutathione peroxidase, catalase, and superoxide dismutase. Non-enzymatic endogenous antioxidants include glutathione, lipoic acid, uric acid, coenzyme Q10, vitamin D, intracellular reducing agents nicotinamide adenine dinucleotide (NAD), and nicotinamide adenine dinucleotide phosphate (NADP). Exogenous antioxidants enter the human organism primarily by nutrition (dietary antioxidants), such as carotenoids; vitamins A1, A2, C, and E; polyphenols (including flavonoids); zinc; and selenium Because different types of antioxidants act in synergy, significantly increasing the number of neutralized free radicals and thus improving the efficiency of antioxidant protection, ingesting and topically applying a wide variety of antioxidants, including carotenoids, is important for skin health.

The Benefits of Soy Ingredients

The safety and benefits of soy ingredients, that preferentially activate beta estrogen receptors (ER-beta), have been known by scientists for decades. It’s time for the rest of the world to catch-up to what scientists understand.

Formulating skin care products containing various soy derivatives has led a number of people to ask me why I would use these products when there are concerns about their health risks. Unfortunately, a hysterical mass media has promulgated these ignorant ideas and social media spreads these false concerns faster and more broadly than a raging wildfire. This is something Dr. Elaine Showalter, Ph.D. taught us about back in the 1990s in her book, Hystories: Hysterical Epidemics and Modern Culture. Sadly, the phenomenon is much worse thirty years hence, benefitting the billionaire media moguls who spread alarming falsehoods with their biased algorithms, but confusing most of the rest. So let’s look at soy benefits in general first, and then I’ll describe their benefits in the skin. Once you read this, you’ll understand why I formulate with soy-based ingredients.

Let’s start with a study about the benefits of soy to general health, from Chen et al (2023) at Harvard Public Health, in a PubMed listed journal, “A higher intake of total phytoestrogens, including isoflavones, lignans, and coumarins, and foods rich in these compounds was associated with lower risk of total and certain cause-specific mortality in generally healthy US adults. These data suggest that these phytochemicals and their dietary sources may be integrated into an overall healthy diet to achieve a longer life span.” This was a large study, following nearly 76,000 women.

Soy contains compounds called isoflavones, which can act as antioxidants in the human body. Antioxidant activity may be responsible for the apparent correlation between soy consumption and lower lipid peroxidation, which can reduce the risk of arterial plaques. Higher antioxidant consumption is also associated with decreased cancer risk.

The three major isoflavones in soy—genistin, daidzin, and glycitin—all have weak estrogenic effects, acting primarily at ER-beta. Known as phytoestrogens, these compounds produce pro- or anti-estrogenic effects by binding to estrogen receptors in the body. Whereas human estrogens bind to both estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ), phytoestrogens prefer ERβ, which accounts for the variations in how they affect different tissues. For this reason, phytoestrogens are referred to as selective estrogen receptor modulators, or SERMs. Selective estrogen receptor modulators affect some cells because the cells have specific estrogen receptors, while other cells are not affected because of different receptor types.

Soy derived isoflavones affect those estrogen receptors that are involved in positive effects – the ERβ subtype that is not involved in cancer. Soy blocks estrogenic effects associated with cancer because the isoflavones block ERα without activating it. Soy is inhibitory to the ill-effects of ERα.

Soy actually controls the growth of cancer cells.

Many studies have reported the anti-cancer effects of soy, for example:

The intake of soybean products in those with BRCA mutation decreased breast cancer risk 47% more than the expected risk.

The point here is that soy is safe, and beneficial in many ways including in better building bone:

Scientists in Germany showed how phytoestrogens (soy) preferentially activate ERβ:

ERβ is not located in liver or uterus, where the negative effects of estrogen have been found. Liver contains only ERα, as does the uterus. The skin contains mostly ERβ

Physiological levels of ingested phytoestrogens are safe for the uterus:

Women consuming the highest levels of soy greatly decreased their chances of cancer:

Soy consumption lessens the ill-effects of menopause:

Postmenopausal women benefit greatly from soy consumption, including better bones and muscle mass, and improved weight.

Here’s a two year study of soy milk versus progesterone or doing nothing (control) for preventing bone loss:

The results find that soy is better than progesterone or doing nothing

The benefits of soy are wide-ranging and documented throughout the world:

Soy does not feminize men – how many times have I heard this nonsense?

Soy is beneficial to children, and may decrease their incidence of cancer:

Soy benefits breast cancer survivors:

Conclusions: In this large, ethnically diverse cohort of women with breast cancer living in North America, a higher dietary intake of isoflavone was associated with reduced all-cause mortality. 

Soy reduces the risk of prostate cancer in men:

Another study of bone loss:

Results: Phytoestrogen increases bone mass equal to or better than HRT:

And this means soy lessens the chance of bone fracture in menopausal women:

Soy also benefits the skin:

Dietary soy protein supplementation with isoflavones may improve skin photoaging, including wrinkles and dyspigmentation, and increase skin hydration in postmenopausal women

The mechanisms of action through which isoflavones in soy benefit the skin are many:

Summary

Organic soy is a great addition to the diet and beenfits the body in many ways, especially as we age and estrogen levels in the body, including the skin, decline. Evidence even indicates it has anti-cancer properties.