No, I'm not a doctor.
I have taken a very extensive look this time. Consider this some kind of second part because there are some sections of the first post that I didn't rehash. We're going to have to summarize this again, but I can still comment on your summary.
After finishing this I felt like it is nitric oxide and what it is related to may be the major factor of breast growth present in women taking antipsychotics and contraceptives. Read about Nitric Oxide, L-Arginine, and Endothelial Function and you will see what I mean. The endothelium is an endocrine organ, and the endothelium even influences angiogenesis and the immune system. These medications can cause vasodilation by removing calcium ions in the cell, so they may be activating something there. Somehow, these medications may be activating hormones, angiogenesis, and immune cells that influence fibroblasts and growth factors all from the endothelium. The endothelium, a monolayer of endothelial cells, constitutes the inner cellular lining of the blood vessels (arteries, veins, and capillaries) and the lymphatic system, and therefore is in direct contact with the blood/lymph and the circulating cells. Of course, even if that is the case, the side effect only happens sometimes to some women. As you said, it may be because some women have more density of receptors in their breasts, such as Estrogen Receptor Alpha. From what I have found in the past, from a chart I made, moderately sized women have the largest breasts and, most likely, the most cases of macromastia and gigantomastia. So, it must be the case that moderately sized women have the most responsive breasts in general, and that is why their breasts grow larger than the breasts of smaller or larger women. Then again, although most larger women only have smaller breasts, an H cup for example, some larger women have breasts that, at a sister size, may be larger than first expected, such as 42R being a 32W. So, it is important to keep in mind that some of this may be somewhat relative. Breast growth takes a long time, it seems to be 10 to 30 months for 1 cup size in macromastia and 1 to 3 months in gigantomachia, however these are just general averages. Because it can take a long time, many tests would have to be conducted simultaneously so that there are more results per year. Because it is untested doesn't mean that it doesn't work, it just means no one has observed it yet. It is neither proven or disproven. We don't know what the effects and the results are. Caution should be taken because we don't know the side effects yet, there is no data, and medication is being taken while the diet is being changed.
I am not saying that the breasts are highly absorbent, in that way, that they are able to absorb water from an external source and be permeable. I am more so saying that when the water reaches the inside of the breasts, the breasts will absorb and disseminate the contents of the water so that it constructs tissue. Skin requires a penetration enhancer (also called sorption promoter or accelerant). That is what the final section or two of this post is about.
I have identified all kinds of other things that will affect the breasts and activate tissue development. Glycoproteins are involved because they interact with cells for various reason including cell adhesion and to help them communicate with one another. Hormones are one way that communication occurs in the body. Collagen is used in the healing process so it will also be involved in tissue development for reparation of an injury.
Yes. What I was saying in the previous post is that the diet and everything applied to the breasts will provide nutrients and promote tissue development from both the inside and the outside. If we find things that have the greatest likelihood of promoting tissue development, then they are included in the diet and anything that provides nutrients to the developing tissue will be present, waiting for the body to use it. We also want to minimize the need for a diet rich in too much of anything because the body can have vitamin poisoning, mineral poisoning, etc. There is only so much the diet will do because none of it is able to target the breasts directly. So, we want to cause all of this nutrients and tissue promoters to be lead to the breasts themselves by having substance absorbed into the breasts. This will help. There will be a spike of substance in the body and the breasts. Hopefully the body will understand the connection, that the reason why the increase in substances in the breasts that are good for tissue development are also related to the substances in the digestive and cardiovascular system. The substances that are absorbed into the breasts will be used by the breasts directly since the breasts regulate themselves, and this should start the tissue development process. The breasts will contain things like hormones, immune cells, peptides, collagen, collagen promoting vitamins, lipids, sugars, etc. Then, the breasts will also receive the nutrients from the digestive and cardiovascular system to sustain and generate more signals in the breasts. Collagen and Elastin will increase, Adipocytes will increase, blood vessels will increase, and maybe some other things. This has the effect of increasing all the necessary tissues and not just one type. Even the hyaluronic acid, for example, will act as a delivery system, a penetration enhancer, a disseminator, and a collagen promoter.
If we take notice of lipoproteins, something becomes clearer. How does a lipoprotein know to send fat to the breasts? Of course, there are other ways that lipids are transported and stored (such as insulin from the pancreas) but this is a good demonstration. Lipoproteins transport lipids (including cholesterol and triglycerides) through the cardiovascular system to cells around the body. Chylomicrons work from the intestines, Very Low-Density Lipoproteins (VLDL) and Low-Density Lipoproteins (LDL)work from the liver, while High-Density Lipoproteins (HDL) work for the liver, and the cholesterol that HDL finds around the body is excreted. Many molecules in the body work for the body. They travel the body but don’t necessarily target the breasts (or any other area) specifically. Of course, some molecules are focused to certain tasks or certain areas. If hormones, lipids, or proteins affect the breasts, how do they target the breasts when they are also working elsewhere? Various things can be produced or received in a woman’s body, but it may not target a specific area. Yet there are times when the breasts are more susceptible to hormones and hormonal changes, such as pregnancy and when a woman is taking hormone-disrupting or endocrine-disrupting substances. But hormones effect women differently and work across the body, so increase in breast size is a limited side effect as it occurs only in certain women. Some women may even have weight gain across the entire body as well as the breasts. Some women may even be able to lose weight everywhere but the breasts. Antipsychotics and birth control may cause an increase in breast size in some women but not in others, and in the women who have increased breast size, it may cause too many adverse effects to be reasonable. This is why it is important that breasts may be able to regulate their region of the body (e.g. the thyroid gland and breasts can accumulate and use iodine). This allows for another method, topical application. If substances are absorbed through the endodermis into the dermis, they would be deep enough to reach breast tissue, mammary glands, and receptors. Here the breasts would be able to make use of them before they enter the into the hypodermis or the rest of the body.
Of course, there are various surgeries that target the breasts such as breast augmentation. Demora Avarice has had these operations, but she has also had less invasive procedures such as saline infusions which, in this case, are like a temporary augmentation. The breasts can be targeted with saline (salt water), which is interesting because salt (sodium chloride) is a common way that iodine is delivered to the body (iodized sodium chloride). There have been many studies in the last decade or so that have researched the effects of breasts absorbing pollutants. Another interesting piece of information is that fat cells produce estrogen. Not only can substances be absorbed by the breasts, but they may continue to promote skin health or produce estrogen within the breast itself.
There are other skin treatments that also help us understand all of this. Most of them are body contouring or sculpting therapies. Laser lipolysis, ultrasound therapy, and RF therapy all work in a similar way. Energies are used to heat skin and compromise adipocytes (fat cells) by damaging their cell membranes causing the fat cells to be broken down and metabolized or removed while the damage activates fibroblasts to promote collagen production and synthesis in the healing process to repair tissue.
Laser lipolysis uses laser energy, typically in the form of low-level laser light (red and near-infrared wavelengths). Ultrasound therapy uses ultrasound waves. Radiofrequency uses radiofrequency energy. The photons are absorbed by mitochondrial chromophores in skin cells and generates heat from vibration, disrupting fat cells to induce a thermal injury response in turn activating fibroblasts that react to this damage. Cryolipolysis and Cryotherapy do the same but with incredibly cold temperatures instead. Radiofrequency (RF) Microneedling combines RF energy and microneedling, the energy and the needle microinjuries cooperate to activate fibroblasts and enhance collagen production through the healing process. Fractional Laser Therapy is like Radiofrequency (RF) Microneedling because it uses laser energy instead of radiofrequency energy, and the laser damages skin with energy instead of metal implements, however, it is only surface level. All these therapies are based on damaging skin, and the problem is that we want to promote all the tissues. Endermologie and Maderoterapia both massage the skin to manipulate the tissues, smooth the skin surface, and remove blemishes (including cellulite). However, they are also removing fat cells and lymphatic fluids. So, breast massages may not be doing anything either unless they are promoting or distributing hormones, which they may not be, and, instead, they may even be reducing the size of the breasts if the breasts aren’t responding well. It is important that, in the promotion of all tissues, that fat cells are provided with fatty acids, glucose, and glycerol. Inflammation must be reduced, possibly in conjunction with adiponectin, to support growth factors including insulin’s synthesis of triglycerides in fat cells. Insulin is a peptide hormone secreted by the β cells of the pancreatic islets of Langerhans. It is interesting that not only is insulin a peptide, but it, sometimes along with adiponectin (a cell-signaling molecule (cytokine) called adipocytokine), is able to make tissue more receptive to lipids and carbohydrates.
Three procedures can more directly promote tissue growth. Platelet-Rich Plasma (PRP) Injections are created by drawing blood and processing it into a concentrate of platelets that is then injected into the tissue. Platelets are a type of blood cell that is involved in the blood clotting process but is also capable of tissue development and repair. Platelet-derived growth factor (PDGF) is released by the platelets at the site of the injury to promote cell proliferation (including fibroblasts and smooth muscle cells), angiogenesis (new blood vessels to deliver nutrients and oxygen), synthesis of ECMCs (including collagen), and cell migration (for the formation of granulation tissue). This enhanced tissue development and repair is like Cell-Assisted Lipotransfer, which is when stem cells are used to aid the development, acceptance, and adhesion of fat tissue and migrated fat tissue. Dermal Fillers are injections containing substances such as hyaluronic acid and collagen. Hyaluronic acid helps to create a favorable, well-hydrated environment for fibroblast cells, which function more effectively when hydrated, collagen production, and collagen synthesis. Hyaluronic acid also prevents collagen degradation and breakdown. Autologous Fat Grafting (fat transfer) uses harvested and processed fat cells from one area of the body that are injected into the breast tissue in layers by cannula through incisions in the breasts. Obviously, moving fat from one area to another is more effective than hoping for hormones to work, which is why Demora Avarice eventually stopped relying on natural or supplemental breast growth stimulants and had breast augmentations by fat transfer. It is clear here that tissue and tissue development itself is more important than providing substances that support signals to be sent for breast development, although these substances are also necessary. One method in particular, Dermal Filler, can provide the glycoprotein collagen and the glycosaminoglycan hyaluronic acid, which are essential to the ECM tissues in the breasts, to the breast tissue. The peptide hormone insulin can support the synthesis of lipids and carbohydrates into the adipocytes. These substances have the greatest support for ECMC development.
Calcium hydroxylapatite, a mineral form of calcium apatite, and poly-l-lactic acid, a polymer form of lactic acid, are also used in dermal fillers. Calcium apatite is calcium phosphate mineral essential to bones and teeth. Hydroxyapatite is essential to the mineralized matrix in bones and teeth., which is why it is used for bone grafts, dental implants, and coatings on orthopedic implants. Calcium Hydroxyapatite is a form of calcium apatite where the hydroxyl ion is present, and microparticles of it can form a scaffold that stimulates fibroblasts, prompting them to produce more collagen. Poly-l-lactic acid also creates a scaffold from microparticles that stimulates fibroblasts, however, it also causes a mild immune response. This response causes the microparticles to be degraded in the phagocytosis process. This leads to the release of natural lactic acid that is metabolized by the body and also stimulates fibroblasts. The metabolization of poly-l-lactic acid causes collagen production.
What’s interesting about poly-l-lactic acid is that it is a polymer, and its natural form is involved in things like glucose synthesis and metabolism. Polymers are molecules composed of chains of monomer units. Proteins (such as enzymes, antibodies, nucleic acids, collagen, and elastin) are polymers comprised of amino acid monomers linked together by peptide bonds. Polysaccharides (such as glycogen, cellulose, and amylase) are polymer carbohydrates composed of sugar units. There are also synthetic polymers such as polyester (carboxylic acid and alcohol monomer units), polyethylene (ethylene monomer units), and polypropylene (propylene monomer units). These three polymers are used to make medical equipment and reconstructive prosthetics.
Polypropylene is also interesting because it is biocompatible and has been tested in polypropylene implants. These implants worked by irritating the skin and causing the production of serous or serosal fluid, serum made by the serous glands or serous membranes (serosa). Serum secretions are rich with proteins (including albumin), electrolytes (including sodium, potassium, chloride, bicarbonate, and magnesium), enzymes (including Matrix Metalloproteinases (MMPs), Plasmin, Hydrolases, Phospholipases), and water. Serous fluid may also contain small amounts of nutrients (glucose and lipids), hormones (insulin, thyroxine (T4), and triiodothyronine (T3)), and waste products (urea and creatine). Serous fluid is primarily used for digestion. Saliva contains mucus and serous fluid. Saliva from most saliva glands contains the enzyme amylase while salivary glands of von Ebner contain the enzyme lipase. Serous fluid can also lubricate the muscles and lungs. Mucins are glycosylated proteins (glycoproteins), proteins themselves are polysaccharides, that are essential to mucus. They are produced by goblet cells in the respiratory and gastrointestinal tracts, as well as other mucous secreting cells. Mucins have a unique structure with a central protein core and extensive glycosylation, making them highly hydrated and viscoelastic. Mucopolysaccharides, or glycosaminoglycans (GAGs), are also polysaccharides with high viscosity due to their negative charge and the ability to attract water. Glycosaminoglycans hydrate and lubricate connective tissue or ECMCS. Examples of Glycosaminoglycans are hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparan sulfate, and keratan sulfate. These molecules often form complexes with proteins to create proteoglycans, which are essential components of the extracellular matrix (ECM). Proteoglycans include Decorin that regulates collagen fibrillogenesis, Versican that hydrates and develops tissue, Biglycan that regulates collagen and tissue development (including tendons), and Syndecan that regulates growth factors. Mucopolysaccharides are also a part of Mucins, and this creates the gel-like properties of mucus that lubricates mucosal surfaces and strengthens mucosal barriers. Therefore, polypropylene would behave as an inflammatory polymer that would be surrounded by serous fluid, a substance containing mucopolysaccharides, and various substances for anti-inflammation and tissue development. Because polypropylene is moisture resistant it would slowly absorb moisture over a long period of time while stimulating proteins, various receptors, and the production of serous fluid, which in turn would mildly effect tissue growth. Interestingly, the two treatments for lopsided breasts in women who had polypropylene implants were fluid drainage and saline infusions. The immune system can help construct or deconstruct ECMCs and connective tissues and the immune response helps understand some of the effects of the polypropylene implant. Macrophages defend against foreign bodies and when their attempts to engulf a foreign body, such as an implant, fail, they resort to forming foreign body giant cells with other immune cells by cytokine response. When the foreign body giant cells also fail to encapsulate and isolate the foreign body, they resort to fibroblasts that create a fibrous encapsulation from collagen. When the encapsulated foreign body remains, and neutrophil enzymes were unable to break down the foreign body, it causes chronic inflammation that contributes to ongoing immune cell activation, the production of fibrous tissue, and angiogenesis (the formation of new blood vessels to supply nutrients and oxygen to the affected area). Polymers, polysaccharides, glucose, lipids, insulin, proteins, collagen, enzymes (MMPs in particular), fibroblasts, glycosaminoglycans, proteoglycans (Decorin, Versican, Biglycan, Syndecan), and water are significant.
Omega-3 Fatty Acid are found in fatty fish and flaxseeds for example. Fatty acids prevent inflammation, which is a known cause of insulin resistance, and by reducing inflammation, these fatty acids may enhance insulin sensitivity. Adipokines, adipocyte signaling molecules, are of particular importance because they can regulate inflammation focused on adipocytes, and fatty acids are able reduce the amount of pro-inflammatory adipokine activity to create a less inflammatory environment. to Even high amounts of triglycerides and other lipids can inhibit insulin, so by improving lipid metabolism and regulating lipid concentrations, fatty acids are able to further improve insulin sensitivity. More importantly, the structure of adipocytes is directly improved using these fatty acids and the cell membrane fluidity developed also allows for better insulin signaling. Fatty acids themselves activates proteins and gene expression involved in insulin response and glucose metabolism. When the number of adipocytes and the health of adipocytes has improved, they release the hormone adiponectin to regulate glucose metabolism. Increase adiponectin levels can improve insulin sensitivity. Algal oil can be obtained as an extract, it is sometimes called vegan omega-3, and some brands contain Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are the most effective insulin supporting fatty acids. This algal oil extract can be applied to the breasts if it has an agent that helps it enter the dermis.
Omega-9 fatty acids are monounsaturated fatty acids. They are essential to cell, the lipid barrier, and water retention for skin health. Omega-9 fatty acids promote “good cholesterol” high-density lipoprotein (HDL) which remove "bad cholesterol” low-density lipoprotein (LDL) from the bloodstream. Omega-9 fatty acids may influence the production and activity of cytokines, which are signaling molecules involved in the immune response. One of the metabolites of oleic acid, is oleoylethanolamide (OEA), which may have anti-inflammatory and metabolic effects. OEA is an endocannabinoid-like compound that interacts with receptors in the body's endocannabinoid system, influencing anti-inflammatory effects. Oleic acid is a free radical scavenger, meaning it can neutralize free radicals in the body. This helps prevent oxidative stress and damage to cells. Free radicals are highly reactive molecules that contain unpaired electrons. This makes them unstable because they are bonding with almost anything. These unstable molecules can damage cell membranes, proteins, and DNA. Antioxidants, including omega-9 fatty acids like oleic acid, work by donating electrons to stabilize free radicals, preventing them from causing damage to cellular structures. Omega-9 fatty acids also contribute to and work with the absorption of fat-soluble vitamins, such as vitamins A, D, E, and K. In the digestive process, dietary fats are broken down into smaller components called micelles. Micelles are essential for the absorption of fat-soluble vitamins because the vitamins are incorporated into the micelles, which provides a suitable environment for these vitamins to dissolve. Palmitic acid is a saturated fatty acid that belongs to the omega-9 family. It can be converted into triglycerides, a form of fat that serves as an energy reserve in adipose (fat) tissue. Excess palmitic acid or saturated fats can cause insulin resistance, inflammation, and cardiovascular diseases (including atherosclerosis).
Magnesium is involved in glucose metabolism and insulin sensitivity. Magnesium can influence the secretion of adiponectin, is involved in the activation of insulin receptors, supports insulin signaling, supports enzymes that breakdown glucose and are involved in the carbohydrate metabolism, and supports glucose transporting molecules. Magnesium also has anti-inflammatory and antioxidant properties, which may also help insulin sensitivity. Glucose transporters (GLUT Proteins) are membrane proteins that accept glucose through the lipid bilayer of cell membranes. Kinases are enzymes that support the translocation of GLUT4 to the cell membrane through the insulin signaling pathway. GLUT4, is mostly found in insulin-sensitive tissues such as adipose tissue, and it is regulated by insulin (and kinases), which allows for increased glucose uptake at the cell membrane. Magnesium serves as a cofactor for enzymes involved in the phosphorylation and dephosphorylation events that regulate glucose transporter activity. Hexokinase and Glucokinase are the enzymes initially involved in glucose metabolism, they phosphorylate glucose and break it down during glycolysis. Kinases are common signal regulators. In cooperation with magnesium as a cofactor, it can influence phosphorylation processes. Dephosphorylation of proteins is also important and phosphates are enzymes that regulate dephosphorylation, and this has effects on insulin action. ATPases are enzymes that hydrolyze adenosine triphosphate (ATP) to release energy. This energy release is essential to energy-dependent cellular processes including insulin signaling. Adenylate Cyclase is an enzyme that synthesizes cyclic AMP (cAMP), a secondary messenger involved in insulin signaling and hormone response. Enzymes in the Krebs cycle, a main energy production pathway, generate energy from nutrients that can be synthesized into adipocytes. Nucleases are enzymes responsible for cleaving nucleic acids. The cooperation between magnesium and enzymes is very important and even affects DNA and RNA polymerases, synthesis of nucleic acids, and gene expression.
Polyphenols such as Resveratrol, Quercetin, and Epigallocatechin Gallate (EGCG) can help insulin pathways. Polyphenols are most known for their ant-inflammatory and antioxidant properties, which can improve insulin sensitivity and glucose metabolism. Resveratrol protects pancreatic Beta-Cells, which are responsible for insulin secretion, slows glucose release by Alpha-Glucosidase, an enzyme involved in carbohydrate metabolism, activates Sirtuin, a protein responsible for metabolism and insulin sensitivity, and supports mitochondrial function. Polyphenols become more interesting when it is apparent that some are polyphenolic phytoestrogens, substances that may influence estrogen or may interact with estrogen receptors. Isoflavones (such as genistein and daidzein), Lignans (such as secoisolariciresinol and matairesinol), and Coumestans (such as coumestrol) are all examples of polyphenolic phytoestrogens. Polyphenols becomes even more interesting when it is also apparent that some have or may have antidepressant properties. Antidepressant Polyphenols include Flavonoids (such as Quercetin and Kaempferol), Stilbenes (such as Reservatrol), Curcuminoids (such as Curcumin), Lignans or Enterolignans (such as secoisolariciresinol), Catechins (such as Epigallocatechin Gallate), and Anthocyanins (such as Cyanidin). They regulate inflammation and oxidation, as well as serotonin and dopamine. Examples of foods containing antidepressant Polyphenols are turmeric, green tea, red grapes, berries (such as strawberries, blueberries, raspberries), apples, onions, broccoli, citrus fruits including (oranges, grapefruits, and lemons), Nuts and Seeds (including almonds, walnuts, and flaxseeds), and Green Leafy Vegetables (such as spinach, kale, and Swiss chard). It is important to remember that phytoestrogens have structures that merely resemble estrogen and they may have little to no effects on estrogen. Phytoestrogens may even inhibit estrogen receptors. However, they may still have some effect, but the other effects are more important. Considering that polyphenols also have insulin and antidepressant effects, which can support adipocytes and prolactin, it seems that polyphenol phytoestrogens have been used in the wrong way and for the wrong reasons this whole time. Because phytoestrogens can also contain fatty acids, insulin enhancers, and antidepressants, they should be used for fat cell increase instead of their supposed effects on estrogen. It would be more effective to apply the phytoestrogens directly to the breasts because it can increase glucose metabolism and fat intake in the breasts and possibly stimulate prolactin, which could further increase breast size. Flaxseed oil seems to have a mild effect on the breasts; however, it could be made more effective if had an agent that helped it to enter the dermis. Flaxseeds seem to have one of the richest compositions with a range of effects.
Here is a review of flaxseed oil as well as sesame seed oil, soybean oil, walnut oil, almond oil, olive oil, and algal oil, which also have rich compositions.
Flaxseed Oil
- Omega-3 Fatty Acid: Alpha-Linolenic Acid (ALA)
- Omega-6 Fatty Acid: Linoleic Acid
- Omega-9 Fatty Acid: Oleic acid
- Polyphenolic Phytoestrogen: Lignan or Enterolignan (Secoisolariciresinol)
- Antidepressant Polyphenol: Lignan or Enterolignan (Secoisolariciresinol)
- Vitamin: E (Alpha-tocopherol)
- Phytosterols: Beta-sitosterol, Campesterol, and Stigmasterol
Flaxseed or Flaxseed Oil reduces inflammation, reduces oxidization, improves adipocytes cell membranes, helps proteins and gene expression, helps produce adiponectin, improves glucose metabolism, supports insulin, is a phytoestrogen, has antidepressant properties, regulates serotonin and dopamine, and influences prolactin.
Sesame Seed Oil
- Omega-9 Fatty Acid: Oleic acid
- Omega-6 Fatty Acid: Linoleic Acid
- Saturated Fatty Acid: Palmatic Acid
- Polyphenolic Phytoestrogens: Lignans (Sesamin and Sesamolin)
- Vitamin: E (Tocopherols and Tocotrienols)
- Phytosterols: Beta-sitosterol, Campesterol, and Stigmasterol
- Moisturizer and Emollient: Squalene
- Minerals: Copper (cofactor for enzyme lysyl oxidas, prolyl hydroxylase, and superoxide dismutase, and affects Collagen and Elastin)
Soybean Oil
- Omega-6 Fatty Acid: Linoleic Acid
- Omega-3 Fatty Acid: Alpha-Linolenic Acid (ALA)
- Polyphenolic Phytoestrogens: Isoflavones (Genistein and Daidzein)
- Antidepressant Polyphenolic Phytoestrogen: Isoflavones (Genistein)
- Vitamin: E (Tocopherols)
- Phytosterols: Beta-sitosterol
- Antioxidants: Ubiquinone (Coenzyme Q10)
- Proteins: All essential amino acids
Walnut Oil
- Omega-3 Fatty Acid: Alpha-Linolenic Acid (ALA)
- Omega-6 Fatty Acid: Linoleic Acid
- Omega-9 Fatty Acid: Oleic acid
- Polyphenols: Flavonoids (Quercetin, Kaempferol, Catechin, Epicatechin)
- Polyphenolic Phytoestrogens: Flavonoids (Quercetin and Kaempferol)
- Antidepressant Polyphenolic Phytoestrogen: Flavonoid (Quercetin)
- Vitamin: E (Tocopherols)
- Phytosterols: Beta-sitosterol
- Protein: L-Arginine
Almond Oil
- Omega-9 Fatty Acid: Oleic acid
- Omega-6 Fatty Acid: Linoleic Acid
- Phospholipids: Phosphatidylcholine (PC), Phosphatidylethanolamine (PE), Phosphatidylinositol (PI)
- Polyphenols: Flavonoids (Quercetin and Kaempferol), Phenolic Acid (Chlorogenic Acid), Stilbene (Resveratrol)
- Polyphenolic Phytoestrogens: Flavonoids (Quercetin and Kaempferol)
- Antidepressant Polyphenols: Stilbene (Resveratrol)
- Vitamin: E (Tocopherols)
- Phytosterols: Beta-sitosterol, Campesterol, and Stigmasterol
- Moisturizer and Emollient: Squalene
Olive oil
- Omega-9 Fatty Acid: Oleic acid
- Vitamin: E (Tocopherols)
- Polyphenols: Secoiridoids (Hydroxytyrosol and Oleuropein)
- Phytosterols: Beta-sitosterol
- Moisturizer and Emollient: Squalene
- Carotenoids: Beta-Carotene (precursor to vitamin A)
- Minerals: Selenium and Iron
Algal Oil
- Omega-3 Fatty Acids: Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA):
- Phospholipids: Phosphatidylcholine (PC), Phosphatidylserine (PS), and Phosphatidylethanolamine (PE)
- Carotenoid: Astaxanthin
- Vitamin: E (Tocopherols)
- Minerals: Iron and Zinc
Berberine is an alkaloid, which is an organic compound primarily used by plants for self-preservation by either defending against being eaten or attracting pollinators. In some ways, because Berberine is found in grapes, berries, and flowers while also activating AMPK, it is like Resveratrol and Magnesium combined as their effects are similar. Berberine reduces inflammation and activates adenosine monophosphate-activated protein kinase (AMPK), an enzyme that senses and regulates energy for cells. When Kinase is activated, it improves glucose uptake in cells and cooperates with insulin to improve insulin sensitivity. Cinnamon contains cinnamaldehyde, cinnamic acid (a phenolic acid), and proanthocyanidins, which may also activate AMPK and support glucose transporters.
In general, topically applied substances can be absorbed into the skin to some extent, but the extent of absorption depends on factors such as the molecular size of the substance, its lipophilicity (ability to dissolve in fats), and the presence of penetration enhancers in the formulation. Lipophilic compounds have an affinity for lipid-based environments, such as the skin's lipid barrier above the endodermis, and can delivery substances deeper into the skin. Lipophilic compounds are usually hydrophobic (repellent to water).
Micelles are structures formed from surfactants (surface-active agents) or phospholipids. The surfactants or phospholipids themselves are polarized, they have a hydrophilic side and a hydrophobic side, and when these amphiphilic molecules self-assemble, they form a sphere with a hydrophilic shell and a hydrophobic core. Oils or fat-soluble compounds, which are both hydrophobic compounds, can be solubilized after being delivered in micelle cores.
Liposomes are a vesicle composed of lipid bilayers that can encapsulate both lipophilic and hydrophilic substances in their aqueous core to deliver them deep in the skin. Active ingredients can be passed through the skin in a more stable and controlled way because the liposome lipid bilayers fuse with cell membrane lipid bilayers. In cooperation with phosphatidylcholine, liposomes can reach the stratum granulosum and sometimes the stratum spinosum. Phosphatidylcholine is a phospholipid, which is a class of lipids (fats) that are essential to cell membranes and lipid bilayers, including those in liposomes. Phosphatidylcholine has a phosphate and choline hydrophilic head and two fatty acid hydrophobic tails. Phosphatidylcholine emulsifies and break down fats and adds structural integrity to liposomal delivery systems. Phosphatidylcholines are synthesized in the body through the Kennedy pathway. The enzyme choline kinase phosphorylates choline to form phosphocholine, this then condenses with cytidine triphosphate to form cytidine diphosphate-choline, which combines with diacylglycerol by enzyme diacylglycerol cholinephosphotransferase to form phosphatidylcholine. Alternatively, glycerol-3-phosphate acylates to form lysophosphatidic acid, this then reacts with cytidine triphosphate and choline to form cytidine diphosphate-diacylglycerol, and phosphatidylcholine is finally created when the phosphocholine transfers to the diacylglycerol backbone. Fatty acids and choline in the diet are essential parts for the production of Phosphatidylcholine. Choline is not a vitamin but it belongs to the vitamin B complex. Liposomes typically aren’t produced in the body and liposomes used in skincare products are typically created through laboratory processes, however, the lipids and phospholipids in their composition share similarities with the natural lipids in cell membranes. This may facilitate interactions with the skin's lipid barrier. formulations with liposomes as delivery systems and phosphatidylcholine can contain a high concentration of liposomes and phosphatidylcholine.
Fatty acids are molecules with a hydrophilic head and a hydrophobic tail, and they have an affinity for fats, and they effectively penetrate the skin barrier and influence substance delivery. They can reach as far as the stratum spinosum and stratum basale above the dermis. They can also repair the stratum corneum by creating lipophilic lamellar structures and integrating into the lipid matrix at the skin’s surface to act as an occlusive agent, which both prevents transepidermal water loss (TEWL) and protects against microparticle or microbe damage. Other good examples of occlusive agents are petrolatum and mineral oil. Palmitic acid is a saturated fatty acid that is an essential part of the lipid barrier and the stratum corneum, which is why substances with palmitic acid may be more easily absorbed in some cases. Fatty acids alter the fluidity and permeability of cell membranes and are good for transdermal drug delivery as they can solubilize hydrophobic compounds and carry lipophilic compounds deep into the skin. Oleic acid is a mono-unsaturated omega-9 fatty acid and the greatest fatty-acid penetration enhancer. Olive oil is rich with oleic acid.
Surfactants and Solvents are substances that are able to disrupt or dissolve surface tension or other substances, including the lipid barrier. Sodium lauryl sulfate, ethanol, propylene glycol, glycerin, and dimethyl sulfoxide (DMSO) are common examples of surfactants and solvents that are used in skincare products, cosmetics, and medications. Propylene glycol is interesting because it is a glycol alcohol containing propylene (C3H8O2) and is related to Polypropylene, which is a propylene polymer plastic consisting of multiple propylene monomer units (C3H6). Propylene glycol is a skin-conditioning agent, solvent, and a humectant. It attracts and retains moisture, which causes it to stay hydrated and prevents formulations from drying out as well as supporting substance delivery. It protects the lipid barrier while also absorbing a litter further than it. Unlike polypropylene that would gather moisture at an incredibly slow rate over time and cause irritation, propylene glycol would send substances through water that would be metabolized in a short period of time. Glycerin (C3H8O3) has one extra hydroxyl group than propylene glycol (C3H8O2) and the two are related so glycerin is a good substitute for propylene glycol. Propylene glycol is usually made from petrochemicals, which can cause skin irritations, while glycerin is made from plants and animals. Diethylene glycol monoethyl ether (DEGEE) has a similar structure (C6H14O3) to propylene glycol and glycerin, however, it is much more harmful because it is a glycol ether, which can cause nerve damage. It is a penetration enhancer used for transdermal delivery of drugs and active ingredients, and it is so effective that it reduces the need for injections and invasive methods because different formulations can enter the epidermis, dermis, and even reach the hypodermis).
Hyaluronic acid is a glycosaminoglycan, a natural component of the skin and it is highly effective at attracting and retaining water molecules, helping to hydrate and maintain moisture in the skin. A Hyaluronic acid with a higher molecular weight will stay closer to the skins surface, while a lower molecular weight can enter the dermis. Hyaluronic acid with a medium molecular weight can reach and hydrate the dermis, while hyaluronic acid with a low molecular weight can enter the dermis and promote collagen production. Anti-aging products, dermal fillers, moisturizers, serums, and masks may contain LMW hyaluronic acid. Glycolic acid, lactic acid, and salicylic acid are possible alternatives and exfoliants that reach the stratum spinosum.
Some peptides in skincare formulations are small enough to reach the stratum spinosum, and because they are collagen and elastin promoters, they can interact with the interact with the extracellular matrix and stimulate collagen and elastin synthesis. Peptides can deliver other substances.
Retinoids such as retinol (Vitamin A) and tretinoin are collagen and elastin promoters and they can support the synthesis of collagen and elastin. They also have antioxidant and regenerative properties, which helps the health of ECMCs and connective tissues. Retinoids can deliver other substances as far as the stratum basale above the dermis, and they can be so effective because they are lipophilic and restore the lipid barrier. Vitamin C is also a collagen promoter with antioxidant properties that can reach the stratum spinosum, close to the stratum basale, but it cannot deliver other substances. Vitamin E is also a helpful antioxidant for skin health. Niacinamide (Vitamin B3) is also a collagen promoter with anti-inflammation effects, however, while it can help other substances be absorbed, it is only able to pass and reinforce the lipid barrier.
Many natural oils such as jojoba oil, argan oil, squalane, evening primrose oil, and rosehip oil are highly lipophilic and highly moisturizing. Argan oil contains omega-9 fatty acid oleic acid, omega-6 fatty acid linoleic acid, palmitic acid, and stearic acid. Evening primrose oil contains omega-6 gamma-linolenic acid. Rosehip oil contains omega-6 fatty acid linoleic acid, omega-3 alpha-linolenic acid, omega-9 fatty acid oleic acid, palmitic acid, and stearic acid as well as collagen promoters vitamin A and vitamin C, and polyphenols (quercetin, kaempferol, rutin, catechin, ellagic acid. Centella Asiatica Extract contains triterpenoid compounds, including asiaticoside, asiatic acid, and madecassic acid, and Flavonoids (Quercetin and Rutin). Triterpenoids contribute to wound healing by promoting collagen synthesis. Asiaticoside, asiatic acid, and centelloside stimulate collagen production. Aloe Vera is also interesting because of its collagen promoting, regenerative, and moisturizing properties. Aloe Vera contains Acemannan and Mannose. Acemannan is a polysaccharide consisting of acetylated mannose molecules and it causes immunostimulation, promotes wound healing, and stimulates fibroblast proliferation and collagen synthesis. Mannose is a monosaccharide, which are used to build carbohydrates, and these are used to form mannose-rich polysaccharides in aloe vera that have moisturizing and hydrating properties. Aloe Vera can regulate macrophages, T lymphocytes, and cytokines. Macrophages regulate the turnover of proteins in the extra cellular matrix, release growth factors (including transforming growth factor-beta (TGF-β)), enzymes, and cytokines which all influence ECMCs and connective tissues, and remove debris and apoptotic cells. T Lymphocytes regulate fibroblasts and release cytokines, which also regulate fibroblasts. Cytokines released by immune cells can affect the endocrine system by influencing the secretion of hormones from endocrine glands. Interleukins and platelet-derived growth factor (PDGF), which are released by various immune cells, also contribute to the regulation of collagen synthesis. The immune response in general also promotes angiogenesis, the formation of new blood vessels, which are essential for supplying nutrients and oxygen to the healing tissue and supporting the activities of fibroblasts involved in collagen synthesis and other reparative processes.
Squalene, is a triterpene, and it is a moisturizer, a component of sebum, and an antioxidant. Squalene is used to synthesize cholesterol and it is a precursor to lanosterol, a tetracyclic triterpenoid, which is essential in the synthesis of cholesterol. Squalene has been used as an adjuvant in some vaccines to improve their effectiveness by promoting a stronger immune response to the active ingredients.
Decorin, Versican, and Biglycan need Vitamin C, Zinc, Copper, growth factor-beta (TGF-β), and amino acids. Syndecan needs sulfate groups (heparan sulfate, chondroitin sulfate, cysteine, methionine, glucosamine) and cytokines. Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases. MMPs are essential for maintaining tissue homeostasis by balancing the synthesis and degradation of ECM components. In cancer, MMPs contribute to tumor invasion and metastasis by degrading the ECM barriers. MMPs are synthesized as inactive proenzymes (zymogens) and require activation, and they are regulated by tissue inhibitors of metalloproteinases (TIMPs). MMPs have been considered as potential therapeutic targets in diseases characterized by abnormal ECM remodeling.
L-Arginine is a semi-essential amino acid amino acid, which means the body can synthesize it, but dietary intake is also necessary. By the enzyme nitric oxide synthase, L-Arginine is a precursor to the synthesis of nitric oxide, which causes vasodilation, delivers nutrients and oxygen, signals immune cells, and regulates inflammation. The immune cells that nitric oxide signals are macrophages, t lymphocytes, natural killer cells, and tumor-infiltrating lymphocytes. L-Arginine is a precursor to polyamines, which are compounds that are involved in cell proliferation and growth, and ribosomes use L-Argine to assemble amino acids into polypeptide chains, which become proteins such as polyamine. L-Arginine supports collagen synthesis and the release of hormones such as insulin and is a precursor to hormones such as growth hormone (GH), and prolactin. L-Arganine is significant to growth, repair, regeneration, immunity, and hormones. Cold pressed avena sativa oat oil contains beta-glucan, a polysaccharide that also effects the immune system, and L-arginine.
Nitric Oxide is important to endothelial function. It requires Oxygen, Nitrate, Nicotinamide Adenine Dinucleotide Phosphate (NADPH) for conversion, Tetrahydrobiopterin (BH4) for function, and Calcium ions and Calmodulin for regulation. NADPH is derived from niacin (vitamin B3) and supported by riboflavin (vitamin B2) and iron. BH4 is synthesised from GTP (guanosine triphosphate) and precursors to folate. GTP is synthesized from guanosine diphosphate (GDP) through a process that involves energy input from adenosine triphosphate (ATP), which is an energy molecule made from glucose. GDP is derived from guanosine monophosphate (GMP). Guanosine diphosphate (GDP) and guanosine monophosphate (GMP) are molecules related to GTP. They are involved in nucleotide synthesis and cellular processes. Guanosine Monophosphate is phosphorylated to form Guanosine Diphosphate, and yet another phosphate group is added, Guanosine Diphosphate is phosphorylated again to form guanosine triphosphate. Guanylate kinase is an enzyme that promotes GTP through the biosynthetic pathway of purine nucleotides. Several vitamins and minerals are involved in nucleotide synthesis, including riboflavin (vitamin B2), folate (vitamin B9), and magnesium. Guanylate kinase is part of the nucleotide salvage pathway, contributing to the recycling of guanine nucleotides within cells. Adenosine triphosphate (ATP) and guanosine triphosphate (GTP) are phosphate donors to GMP and GDP. ATP is created in a very similar way to GTP. ATP is created from two phosphorylations, from adenosine monophosphate, and from adenosine diphosphate by the enzyme adenylate kinase.
Omega-6 fatty acids are polyunsaturated fatty acids. They are essential to cell membranes (the brain in particular), the lipid barrier, and water retention for skin health. Linoleic acid is a precursor for the synthesis of prostaglandins, which are hormone-like substances involved in inflammation, vasodilation, and blood clotting. Prostaglandins are both pro-inflammatory and anti-inflammatory. Prostaglandins are eicosanoids, which are lipid-based signaling molecules that play a unique role in immune responses. Unlike hormones that travel through the bloodstream to exert their effects, prostaglandins act locally in the tissues where they are produced. This allows them to have specific and immediate effects on nearby cells. Prostaglandins contribute to the reduction of autoimmune disorders by influencing immune tolerance, which is the ability of the immune system to recognize and tolerate the body's own tissues. Prostaglandins sensitize nerve endings to pain, contributing to the perception of pain. They also play a role in the regulation of body temperature and can contribute to the development of fever. Certain prostaglandins help maintain the integrity of the gastrointestinal mucosa. Prostaglandins are involved in the reproductive system, including the induction of labor during childbirth, regulation of menstrual cycles, and control of blood flow to the uterus. Prostaglandins contribute to the regulation of salt and water balance in the kidneys. Immune cels that are signaled are macrophages, T lymphocytes, B lymphocytes. Prostaglandins can stimulate the activity of fibroblasts, promoting the synthesis of new connective tissue (collagen in particular), and can stimulate angiogenesis and help provide immune cells, growth factors, and nutrients by vasodilation. Arachidonic acid (ARA) is an omega-6 fatty acid that serves as a precursor for the synthesis of various signaling molecules, including prostaglandins and leukotrienes. The primary precursors for arachidonic acid are linoleic acid and eicosapentaenoic acid (EPA). Arachidonic acid is a precursor for prostaglandins. Linoleic acid and eicosapentaenoic acid are converted into arachidonic acid through a series of enzymatic reactions involving desaturases and elongases. Nutrients like iron, zinc, magnesium, and vitamins B3, B6, and B12 support the enzymatic processes involved in the conversion of precursor fatty acids to arachidonic acid. Maintaining a balanced ratio of omega-3 to omega-6 fatty acids is important for overall health because EPA is metabloized to form pro-resolving mediators (SPMs), which regulate pro-inflammation prostaglandins.
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