Sex, Gender and Disorders

Dr. James Manos (MD)

July 24, 2018

Sex, Gender, and Disorders

The distinction between biological sex, gender identity, gender expression & gender as a role. Also, about the XY sex-determination system, genitalia, gonads, gametes & sexual characteristics

(the terminology was confusing ever for me, although I am familiar with medical issues)

The XY sex-determination system characterizes humans, most other mammals, some insects such as Drosophila (fruit fly), and some plants such as Ginkgo (such as Ginkgo biloba, a famous memory booster herb). In this system, the sex of an individual is determined by a pair of sex chromosomes, also called gonosomes. A chromosome is a packaged and organized structure containing most of the DNA of a living organism. DNA is the abbreviation of deoxyribonucleic acid; chemically, it is a nucleic acid. DNA is a molecule that carries most of the genetic instructions used in developing, functioning, and reproducing all known living organisms and many viruses. Males have two distinct sex chromosomes (XY) and are of heterogametic sex, while females have two of the same kind of sex chromosomes (XX) and are of homogametic sex.

Colloquially, sex and gender are often used interchangeably! However, these terms are not precisely the same. The distinction between sex and gender differentiates sex from gender Sex refers to the anatomy of a person’s reproductive system and the secondary sexual characteristics. In contrast, gender relates to either social roles based on the sex of the person (gender role) or personal identification of one's own gender based on an internal awareness (gender identity). Gender roles and identity may not coincide with the individual's sex. A case in which a person's assigned sex and gender do not align is a transgender person (mentioned below). Among scientists, the term ‘sex differences,’ as compared to ‘gender differences,’ is typically applied to evolved sexually dimorphic traits.

Genitalia, gonads & gametes

The Latin term ''genitalia,'' also known as ''genitals,'' refers to the externally visible sex organs, known as primary genitalia or external genitalia. In male mammals, these are the penis and the scrotum, while in female mammals, these are the clitoris and the vulva. The hidden, not visible, sex organs are called secondary genitalia or internal genitalia. The most important are the gonads, a pair of sex organs, specifically the testes in male mammals and the ovaries in female mammals. Gonads are the real sex organs, generating reproductive gametes, sperm in males, and ova (eggs) in females, containing inheritable DNA in the XY male sex chromosomes and XX female sex chromosomes. There are some rare genetic exceptions related to sex chromosomes, such as the Turner syndrome in females with XO sex chromosomes and the Klinefelter syndrome in males with XXY sex chromosomes.

Gonads additionally produce most of the primary hormones that affect sexual development and regulate other sexual organs and sexually differentiated behaviors. These sex hormones are androgens, such as testosterone, in males and estrogens (estradiol, estrone, and estriol, with estradiol being the most potent and prevalent) and progesterone in females. A gamete is a cell that fuses with another cell during fertilization (conception) in organisms that sexually reproduce. Everyone produces only one type of gametes in species that produce two morphologically distinct gametes. Therefore, females produce the larger class of gamete called an ovum, known colloquially as an ‘egg,’ while male produces the smaller called sperm.

About secondary sexual characteristics

While humans are born with apparent primary sex characteristics directly concerned with reproduction distinguishing males from females, such as the penis in men and the vagina in women. On the other hand, secondary sexual characteristics appear at puberty, such as pubic hair, breast development in females, and beards in males.

In men, secondary sexual characteristics include pronounced body hair characteristics (body hair, usually coarse; beard; facial hair; chest, axilla, abdominal, pubic area hair); heavier musculature than women; angular features (such as the square jaw, triangular mid-region; something like Sylvester Stallone); narrow hips; muscular pectorals (chest muscles); overall, less fat tissue; deeper voice; larynx (windpipe) enlargement (‘Adam’s apple’); broadening of shoulders and chest (shoulder span is wider than hip span), acne (that, when excessive, needs treatment to prevent scars), higher waist-to-hip ratio, and penis enlargement. I think the last change is the most striking and apparent!

In women, secondary sexual characteristics include less pronounced body hair characteristics (mostly in the pubic region, hair is usually finer); lighter musculature; rounded features (i.e., softer facial features, hourglass mid-region); wider pelvis (for childbearing); more pronounced breasts with more fatty tissue; overall, more fat tissue; and higher-pitched voice.

Gender is the range of characteristics differentiating masculinity from femininity, including biological sex (i.e., the state of being male, female, or intersex), sex-based social structures (including gender roles and other social roles), and gender identity.

The distinction between biological sex & gender as a role

In 1955, the sexologist John Money introduced the terminological distinction between biological sex and gender as a role. Money's meaning of the word ‘gender’ did not become widespread until the 1970s when feminist theory embraced the concept of a distinction between biological sex and the social construct of gender. However, even today, the terms ‘gender’ and ‘sex’ are often used interchangeably.

Gender role

The term 'gender role' was first coined by the sexologist John Money in 1955 during his study of intersex individuals. A gender role is a set of societal norms that determine which type of behavior is considered acceptable, appropriate, or desirable for an individual based on their actual or perceived sex and the personal conception and expectation of femininity and masculinity. The gendered expectations may vary substantially among cultures.

Gender identity

Gender identity is our personal experience and sense of gender, referring to being a man or a woman. Notably, some individuals do not identify themselves with some, most, or all of the aspects of gender that are assigned to their biological sex. In most Western societies, there is a gender binary, meaning a social differentiation related to the ideals of masculinity and femininity in all aspects of sex and gender: biological sex, gender identity, and gender expression.

Some societies have 3rd gender categories that can be used by individuals uncomfortable with their gender associated with their sex.  Gender identity is usually formed by age three and is unlikely to change after that milestone. The formation of gender identity usually concludes between the ages of four and six. Gender identity is affected by social factors as well as individual perceptions and preferences. 

Consequently, a three-year-old infant can self-identify as a boy or a girl, even without fully understanding the implications of gender completely! Studies suggest that children develop gender identity in three distinct stages: The first stage involves toddlers and preschool children affected by socialized aspects of gender. The second stage, around the ages of 5–7 years, is a consolidation phase in which identity becomes rigid. After this peak of rigidity follows the third stage in which fluidity returns and socially defined gender roles play a less critical role. 

Sex assignment

Sex assignment, also known as gender assignment, is the discernment of the sex at the birth of a baby. The act of sex assignment is considered an observation or recognition. In most births, a medical professional (a physician, obstetrician, or pediatrician; a midwife or a nurse), or a relative, inspect the genitalia (genitals) visually when the baby is delivered, determining, without the expectation of ambiguity, the baby's gender: male or female. Sex assignment may also be done before birth with the help of ultrasonography.

In most cases, the gender of rearing of the child matches the assigned gender affecting the future expectation of gender identity.  However, in some cases, the assigned sex based on observation may be incorrect, as in the example of transgender or intersex individuals in whom gender identity is not consistent with the assigned sex or sex of rearing! In some cases, termed ''intersex,'' the internal anatomy may not be compatible with the sex assignment based on observation of external anatomy. 

Sexual orientation

Sexual orientation is an enduring pattern of romantic or sexual attraction, or a combination of these, to persons of the opposite sex or gender, the same sex or gender, or to both genders and more than one gender (see above for the difference between sex & gender). According to the American Psychological Association, sexual orientation is related to an individual's sense of identity based on romantic or sexual attractions, associated behaviors, and social interaction with others who share those attractions. 

These attractions related to sexual identity are generally classified as heterosexuality, homosexuality, bisexuality, and asexuality (= the lack of sexual attraction to others). Additionally, some may label themselves as ''pansexual'' or ''polysexual.''

Sexual preference

The term sexual preference overlaps with sexual orientation and may contain a voluntary choice, although the scientific consensus is that sexual orientation is not a choice. However, sexual preference and sexual orientation are distinguished in psychological research. For instance, an individual who self-identifies as bisexual may sexually prefer one sex over another.

Medical diseases that affect gender identification

Medical diseases that affect gender identification include virilization, intersex or ambiguous genitalia, gynandromorphs, true hermaphroditism and pseudohermaphroditism, and gonadal dysgenesis. They also include medical disorders that involve intersex anatomies, such as inherited (gene-related) conditions and endocrinological diseases that may also be inherited or may be acquired. 

It is essential to have in mind that the final body appearance (called phenotype) does not always comply with what is written in the genes and their DNA sequence. Consequently, sometimes there is a discrepancy between genetic (or chromosomal) and phenotypic (or physical appearance) sex. Additional factors may influence sexual differentiation. For instance, the Intersex Society of North America challenges the XY sex-determination system’s assumption that chromosomal sex determines a person's ''original'' biological sex. 

Virilization in medicine is the biological development of sex differences, changes that make a male body different from a female. Most of the variations of virilization are produced by hormones called androgens. Virilization occurs in three conditions: prenatal sexual differentiation, the postnatal changes of normal male puberty, and the excessive androgen effects in males or females.

Feminization in medicine is the development of an organism with physical characteristics unique to females and may represent a standard development process contributing to sexual differentiation. In animals and humans, when feminization occurs in a male or at an inappropriate developmental age, it is often because of an acquired endocrinological disorder or a genetic, congenital (inherited) chromosomal disorder. An example of abnormal feminization is gynecomastia (= the inappropriate development of breasts unrelated to fat tissue in obese people called pseudo-gynecomastia) which may result from elevated levels of female hormones such as estrogens. Another cause of feminization is a deficiency or blockage of virilizing hormones (androgens).

''Intersex,'' in humans and other animals, is a variation in sex characteristics, including chromosomes, gonads, or genitals (described above), that does not allow an individual to be distinctly identified as a male or a female. Such variation may involve genital ambiguity and combinations of chromosomal genotype and sexual phenotype other than XY (male) and XX (female). Intersex infants and children, such as those with ambiguous external (outer) genitalia, may be treated surgically and/or hormonally to achieve more socially acceptable sex characteristics (always when the individual feels uncomfortable with this condition). However, there is a controversy regarding this issue and the favorable outcome of the ''correction.'' 

Research in the late 20th century indicates that diverse intersex bodies are normal, relatively scarce forms of human biology. Intersex people have various gender identities; most identify as male or female, while some may recognize them as neither exclusively male nor solely female. Noteworthy, some intersex individuals may be raised as a male or a female but may identify with another gender later in life!

Ambiguous genitalia (genitals) appear as a large clitoris or small penis. Because there is variation in the development of the sex organs, a child can be born with sexual anatomy typically female or feminine in appearance with a larger-than-average clitoris (called ''clitoral hypertrophy'') or typically male or masculine in appearance with a smaller-than-average penis (called ''micropenis'') that is urinary opening (called ''meatus'') open along the underside (called ''hypospadias''). Specifically, hypospadias refers to a birth defect of the urethra in the male where the urinary opening is not at the usual location on the head of the penis, but, in about 90 percent of cases, the opening (meatus) is on or near the head of the penis (glans), while on the remaining cases, the meatus is near or within the scrotum. Epispadias is another rare birth defect of the penis in which the urethra ends in an opening on the upper aspect (the ''dorsum'') of the penis.

Genitalia may be ambiguous, such as female genitals with a very large clitoris and partially fused labia or male genitals with a very small penis, completely open along the midline (hypospadias; see above), and empty scrotum. Fertility in these cases is variable. According to some scientists, the distinctions "male pseudohermaphrodite," "female pseudohermaphrodite," and especially the term "true hermaphrodite are obsolete and outdated terms of the 19th century, while others believe define the terms "male pseudohermaphrodite," and "female pseudohermaphrodite" the gender in terms of the histology (microscopic appearance) of the gonads (testes (some also call them ''testicles'') or ovaries).

True hermaphroditism is defined as the appearance of both testicular and ovarian tissue. This is not only observed in humans but also in other species. For instance, in 2003, researchers at UCLA University published a study referring to a lateral gynandromorphic Zebra finch (a bird that lives in Australia, Indonesia, and East Timor), which had a testicle on the right and an ovary on the left. Its entire body was split between female and male, with hormones from both gonads running through the blood. This is a very rare example of ''mosaicism'' (= the presence of two or more populations of cells with different genotypes in one individual who has developed from a single fertilized egg) or ''chimerism'' (chimera is a single organism composed of genetically distinct cells; this can result in male and female organs, two blood types, or subtle variations in form).

Importantly, there are no documented cases in which both types of gonadal tissue function. Encountered karyotypes (= the number and appearance of chromosomes in the nucleus of a eukaryotic cell, i.e., a cell that contains a nucleus and other organelles enclosed within membranes) include 47XXY, 46XX/46XY, or 46XX/47XXY, and various degrees of mosaicism including an unusual case of an XY predominant (96 percent) mosaic giving birth. Although many, if not most, medical textbooks mention that true hermaphroditism in humans does not exist, in fact, this condition is infrequent, but it does exist. For example, a search in the PubMed medical database reveals some cases, such as the one published on http://www.ncbi.nlm.nih.gov/pubmed/25295140   

Pseudohermaphroditism is the condition in which an organism is born with primary sex characteristics of one sex but develops secondary sex characteristics that are different from what would be expected based on the gonadal tissue (ovary or testis). Sometimes, the external sex organs appear intermediate between a typical clitoris and penis. In contrast, in other cases, the external sex organs have an appearance that would be expected to be seen with the "opposite" gonadal tissue. For this reason, pseudohermaphroditism is sometimes not identified until puberty or even until adulthood.  The term "male pseudohermaphroditism" is used when a testicle is present, and the term "female pseudohermaphroditism" is used when an ovary is present.

Associated medical conditions in males include 5-alpha-reductase deficiency. An ''ovotestis'' is a gonad (a reproductive gland) with both testicular and ovarian aspects. In humans, ovotestes are an anatomical abnormality associated with ''gonadal dysgenesis.'' There are various forms of ovotestes, such as having two ovotestes or one ovary and one ovotestis, often in the way of streak gonads. The phenotype (= the set of observable characteristics of an individual resulting from the interaction of its genotype with the environment) is not determinable from the ovotestes. In some cases, regarding genital development, the appearance is "fairly typically female," while in others, it is "fairly typically male," or it may be "fairly in-between.

Gonadal dysgenesis is any congenital (= a condition existing at or before birth, regardless of cause) developmental disorder of the reproductive system characterized by a progressive loss of germ cells (= any cell that gives rise to the gametes, i.e., sperm and ovum in humans, of an organism that reproduces sexually) on the developing gonads (reproductive glands) of an embryo (fetus).  This loss leads to extremely hypoplastic (underdeveloped) and dysfunctioning gonads, mainly composed of fibrous tissue called ''streak gonads.'' An example of this defection is a form of aplasia (= defective development or congenital absence of an organ or tissue) in which the ovary is replaced by functionless tissue. 

The accompanying hormonal failure also prevents the development of secondary sex characteristics (described above) in either sex, resulting in a sexually infantile female appearance and infertility. An example of gonadal dysgenesis is Turner’s syndrome (XO) in females that are typical of short stature and have specific facial and body features (such as a short and webbed neck, low-set ears, low hairline at the back of the neck, short stature, and swollen hands and feet) and are infertile.

According to the ‘Intersex Society of North America,’ examples of medical disorders that sometimes involve intersex anatomy (although these conditions are not always intersex) are the following:

•    5 – alpha-reductase deficiency

•    Androgen insensitivity syndrome

•    Aphallia (absence of penis)

•    Clitoromegaly (clitoris enlargement)

•    Congenital adrenal hyperplasia

•    Gonadal dysgenesis (partial & complete)

•    Hypospadias (described above)

•    Klinefelter syndrome (47, XXY)

•    Micropenis (small penis < 8 cm)

•    Mosaicism (described above) involving sex chromosomes

•    Ovotestes (described above)

•    Partial androgen insensitivity syndrome

•    Progestin-induced virilization

•    Swyer syndrome

•    Non – Klinefelter XXY

•    17 – beta-hydroxysteroid dehydrogenase deficiency

•    Cryptorchidism (the testicle or both testes have not descended to the scrotum but remain in the abdominal area)

For an extended list of the disorders affecting sexual development, you may visit:

•    https://en.wikipedia.org/wiki/Disorders_of_sex_development

Thanks for reading!

   

Cosmetics for Wrinkles & Hair Loss

Dr. James Manos (MD)

July 21, 2018 

Cosmetics for wrinkles & hair loss

Image (free to use):   Nepali woman photographed on the Annapurna Circuit in Ghyaru. (October 18, 2012). Source for the image: Author: Nepali_woman,_Ghyaru.jpg: travel way of life derivative work: Bruce1ee. Uploaded by the user: Bruce1ee. Source: Wikipedia. Link: https://en.wikipedia.org/wiki/File:Nepali_woman,_Ghyaru_(crop).jpg

I) Cosmetics for wrinkles

Introduction

The worst enemy for our skin that predisposes us to skin aging, including wrinkles, is the sun! It is also a cause of skin cancer (including melanoma, which is an aggressive type of cancer), skin photosensitivity (allergic reaction from sun exposure), and eye cataract. A high SPF sunscreen for protecting our skin against UV (ultraviolet) sunbeams is essential before exposure to the sun (there are special sunscreens for the face). However, we should not avoid the sun completely, as it is essential for absorbing the vitamin D important for our bones (such as calcium).


Overview

Extrinsically aged skin shows signs of photodamage (damage from sunlight – especially UVB), including wrinkles, pigmented lesions, actinic keratoses, and patchy hypopigmentations. Therapeutic modalities imply photoprotection (protection from sunlight) with sunscreens that prevent sunburn and block ultraviolet irradiation. Other modalities include retinoids, which regulate gene transcription with subsequent cellular differentiation and proliferation. The topical and peroral administration of network antioxidants, such as vitamins E and C, coenzyme Q10, alpha-lipoic acid, and glutathione, enhances the antiaging effect. The other antioxidants, such as green tea, dehydroepiandrosterone (DHEA), melatonin, selenium, and resveratrol, also have anti-aging and anti-inflammatory effects. Topical bleaching agents such as hydroquinone, kojic acid, and azelaic acid can reduce signs of aging. Studies confirm the efficacy of these topical agents in combination with superficial or medium depth or deep peeling agents for photodamaged skin treatment. Indications for the type of chemical peels according to various clinical diagnoses are given, as well as the advantages and disadvantages of diverse types of chemical peels. (Reference: http://www.ncbi.nlm.nih.gov/pubmed/20977120  )

Skin aging & photodamage (damage from sunlight) prevention

The main reason for wrinkles is the sun, so protection from the sun is mandatory, although it is vital for activating vitamin D and preventing osteoporosis! Most people ignore this, as they do not protect their skin from the sun. To prevent skin aging, it is recommended to avoid the sun, which causes aging and skin cancer (including melanoma). Wearing dark glasses that absorb ultraviolet radiation prevents cataracts. Also, a sunscreen of high SPF (e.g., more than 50) and a special sunblock for the face is needed to prevent skin cancer. The deficiency of the ozone layer atmosphere has increased skin cancer rates.

Makeup

Most women, but also some men, use makeup on their faces. However, it closes the skin's pores and does not let it ''breathe'' (like the transpiration of plants).  So, it is better to prevent wrinkles with face creams and serums so that you will not need to cover them with makeup.


Electric devices such as ‘pens’ with low–level laser, radiofrequency (RF), microcurrent, and massagers

For skin wrinkle treatment, on the market, someone can find specially patented pens with low–level laser alone or with microcurrent. Also, on the market, someone can find electric vibration anti-wrinkle eye & face skin massagers. I advise against the use of laser pens by other than beauticians or skin doctors, as the laser may damage the eye (thus, special black glasses are needed) and damage the skin if not used properly. Also, experts use expensive professional lasers or other devices for more appropriate and safe wrinkles from the cheap ones that can be purchased on the web.

Α study investigated using a 975 nm diode laser for skin tightening. The study included the medical records of seventeen patients undergoing photothermal laser therapy to correct deformities in the cervicofacial region. Four cervicofacial lines were measured preoperatively (baseline), immediately after treatment, and 3 months post-treatment with a caliper. The results demonstrated a significant skin tightening in all patients 3 months after the procedure. The study concluded that using a 975 nm diode laser resulted in skin tightening. (Reference: http://www.ncbi.nlm.nih.gov/pubmed/26751918 )

A study evaluated patients after treatment by evaluating the efficacy and safety of the newest generation of monopolar radiofrequency (mRF) devices. Sixty-four patients with mild to moderate facial skin laxity were treated using the new mRF with vibration handpiece. Patients were surveyed between 1 and 10 months after treatment. The study concluded that a new monopolar RF (mRF) system was safely tolerated and efficacious for most patients at facial treatment sites. (Reference: http://www.ncbi.nlm.nih.gov/pubmed/23153312 )

Natural treatments

Introduction

Sleep

A night of good sleep is essential for our cells. It may have anti-aging effects! Adequate sleep is something that, for most people, is a necessity, as most have low quality or quantity of sleep. In adolescence, GH (growth hormone) is secreted during sleep and plays a vital role in development. But it also has anecdotal wrinkle prevention or healing effects.

In growth, growth hormones are typically released during sleep. Growth hormones are suppressed if someone consistently gets too little sleep (known as "sleep deprivation"). Lack of sleep also can affect other hormones. Studies show that sleep deprivation is linked to obesity and diabetes. (Reference (Retrieved July 21, 2018):   https://kidshealth.org/en/teens/sleep-growth.html )

Insomnia hormone imbalance or sleeplessness is both a cause and effect. Hormone imbalance resulting from perimenopause, menopause, adrenal fatigue, or other symptoms may cause sleeplessness, which worsens the hormone imbalance. Insomnia (sleeplessness) also has many other non-hormone-related causes. (Reference (Retrieved July 21, 2018):  https://www.bodylogicmd.com/for-women/insomnia-hormones-sleeplessness )

Sleep is vital for the growth and renewal of multiple physiological systems. A study evaluated the effect of chronic poor sleep quality on skin health and aging measures. Self-perceived satisfaction with appearance was also assessed. In the study, sixty healthy Caucasian women were categorized as poor- or good-quality sleepers. The results showed that good sleepers had significantly lower intrinsic skin aging scores by SCINEXA(TM). The study concluded that chronic poor sleep quality is associated with increased signs of intrinsic aging, diminished skin barrier function, and lower satisfaction with appearance. (Reference:  https://www.ncbi.nlm.nih.gov/pubmed/25266053 )

Some may wonder if sleep position affects wrinkle development. A study was conducted to determine whether there is an association between sleep position and the appearance of facial wrinkles and facial descent. The study concluded that sleep-side preference was not significantly correlated with wrinkles or facial descent. (Reference: https://www.ncbi.nlm.nih.gov/pubmed/23865987  )

Peeling

Peeling is said that helps in treating wrinkles. Instead of peeling, someone can use a subtle face cleansing cream with panthenol (vitamin B5), chamomile, and allantoin. Otherwise, a special cleaning soap may be used, but I do not opt for chemical peeling.

Weight reduction

Being obese and overweight obviously hides the wrinkles as the skin stretches because of the adipose (fat) tissue. However, it is accompanied by many adverse health effects, most importantly cardiovascular and metabolic (including diabetes). Weight reduction should be targeted cautiously as the skin becomes loose or saggy when it is abrupt, and wrinkles worsen. That is why contrary to the past, liposuction is often combined with other plastic surgery procedures such as abdominoplasty ("tummy tuck" surgery). For people on a diet, the ideal is not to lose more than 0.5 to 1 kilogram (1.1 pounds to 2.2 pounds or 0.078 stones to 0.157 stones) weekly, with the former (0.5 kg) being preferable to the latter (1 kilogram) meaning that the more gradual weight loss is better than the abrupt regarding the risk of developing wrinkles because of skin laxity!

Cosmetics for wrinkles contain ingredients such as hyaluronic acid, collagen, retinol (it should be used only at night as it may cause skin redness from the sun & also a sunscreen with high SPF, as well a skin moisturizer should be used), and polypeptides, including copper peptides, hexapeptides and argireline® (acetyl hexapeptide -3).

Natural supplements they are used for wrinkles include vitamins C & E (antioxidants), pomegranate and Royal jelly, walnut oil, avocado oil, sweet almond oil, rose oil, argan oil, sea buckthorn oil, extra virgin olive oil, evening primrose oil, sesame oil, pomegranate seed oil, aloe vera oil, rosemary oil, and Chios Island mastic (plant resin) oil.

Hyaluronic acid (hyaluronate)

Hyaluronic acid (hyaluronate) is very efficient for wrinkles, and experts such as dermatologists (skin doctors) often use hyaluronic injections for skin wrinkles (skin fillers).

A study evaluated the anti-wrinkle effect of a preparation containing human growth factor and hyaluronic acid serum on periorbital (around the eye) wrinkles (crow's feet). In the study participated 23 Korean women (39-59 years old) who were not pregnant, nursing, or undergoing any concurrent therapy. All the patients completed an 8-week trial of twice-daily application of human growth factor and hyaluronic acid serum on the entire face. The results showed that periorbital wrinkles significantly improved after treatment, with improvements noted by the physician's assessment and visiometer analysis. The study concluded that topical application of human growth factor and hyaluronic acid was beneficial in reducing periorbital wrinkles. (Reference: https://www.ncbi.nlm.nih.gov/pubmed/25260051 )

A study tested the intradermal HA hyaluronic acid (HA) injection method to place multiple HA struts by (1) inserting a small needle perpendicularly to the wrinkle and (2) injecting HA as intradermal struts with the skin fully stretched by the practitioner's fingers. The results of both nasolabial folds (NLFs) in ten patients suggest that this technique improves nasolabial folds (NLFs) and maintains the effects more consistently than conventional techniques. However, the effects of both methods were almost lost after six months. (Reference: http://www.ncbi.nlm.nih.gov/pubmed/26893992 ).

    Hyaluronic acid is also used in face creams and is useful for wrinkles. Hyaluronic acid is a ‘heavy’ (regarding its molecular weight) carbohydrate polymer. New forms are used today, such as nano-hyaluronic acid.

A study evaluated the efficacy of a new topical low molecular nano-hyaluronic acid preparation in treating wrinkles, skin hydration, and skin elasticity in humans. Thirty-three women with an average age of 45.2 were studied for eight weeks to measure the anti-wrinkle efficacy of a new nano-hyaluronic acid. The measurements were performed in the periorbital (around the mouth) regions by investigating the three-dimensional structure using a DermaTOP for wrinkles. The study concluded that new nano-hyaluronic acid clearly demonstrated a significant benefit in decreasing the depth of wrinkles (up to 40 percent), and skin hydration (up to 96 percent), and skin firmness and elasticity were significantly enhanced (up to 55 percent) at the end of eight weeks. (Reference: http://www.ncbi.nlm.nih.gov/pubmed/24688623 )

(Hydrolyzed) collagen

Collagen is also used for wrinkles in special creams.

A randomized, double-blind, placebo-controlled clinical trial of ingestion of two types of collagen hydrolysates, which are composed of different contents of the bioactive dipeptides, prolyl-hydroxyproline (Pro-Hyp) and hydroxyprolyl-glycine (Hyp-Gly), to investigate their effects on skin condition improvement. The study concluded that the collagen hydrolysate with a higher content of prolyl-hydroxyproline (Pro-Hyp) and hydroxyprolyl-glycine (Hyp-Gly) showed more improvement in facial skin condition, including facial skin moisture, elasticity, wrinkles, and roughness. (Reference: http://www.ncbi.nlm.nih.gov/pubmed/26840887 )

Vitamins (A, C, E, B3 & provitamin B5)

Vitamins may also ameliorate wrinkles, including vitamins A, C, and E (called ‘ACE’ and are antioxidants), vitamin B3, and provitamin B5 (also called panthenol).

A study assessed the facial skin effects in Indian women of the daily use of a lotion containing niacinamide (vitamin B3, also called niacin, nicotinic acid, and nicotinamide), panthenol (provitamin B5), and tocopherol acetate (vitamin E activity) using quantitative image analysis. Adult women aged 30-60 with epidermal hyperpigmentation were recruited in Mumbai and randomly assigned to apply a test or control lotion to the face daily for ten weeks. The study concluded that daily use of a facial lotion containing niacinamide (vitamin B3, also called niacin, nicotinic acid, and nicotinamide), panthenol (provitamin B5), and tocopheryl acetate (vitamin E activity) improved skin tone and texture and was well tolerated in Indian women with facial signs of aging. (Reference: http://www.ncbi.nlm.nih.gov/pubmed/20061726 )

Chemical Peeling

Chemical peeling is another method experts (dermatologists & beauticians) use for face wrinkles.

A study investigated the effects of chemical peeling and the mechanism of wrinkle reduction in photoaged hairless mice skin. After inducing photoaged skin in hairless mice by repetitive ultraviolet-B irradiation applied over 14 weeks, the scientists applied trichloroacetic acid (TCA) 30 percent, TCA 50 percent, and phenol on areas of the same size on the backs of the mice. Punch biopsies were obtained 7, 14, 28, and 60 days after the procedure for histologic and immunohistochemical analyses. The study concluded that chemical peeling reduces wrinkles and regenerates skin by increasing the dermal (skin) thickness and the amount of collagen and elastic fibers in photoaged (aged from sunlight) skin. (Reference: http://www.ncbi.nlm.nih.gov/pubmed/22126868 )

Retinoids (tretinoin & retinol)

Retinol is the most crucial topical treatment for wrinkles.

Retinoids such as tretinoin (also known as all-trans retinoic acid, ATRA, a pharmaceutical type of retinoic acid, a metabolite of retinol that is vitamin A), and retinol (a form of vitamin A synthesized from the breakdown of beta-carotene) is the most effective treatment for facial wrinkles and is used in face & eye creams.

Retinol, a precursor of retinoic acid, has immense potential as a topical anti-aging molecule. A study assessed the efficacy and safety of 0.1 percent stabilized retinol on photodamaged skin during a one-year treatment. The investigation included two 52-week, double-blind, vehicle-controlled studies. In the primary study, sixty-two subjects applied either a stabilized retinol formulation or its vehicle to the full face. A second exploratory study evaluated histological/histochemical markers in twelve subjects after 52 weeks of either retinol or vehicle use on contralateral dorsal forearms. The study's results showed that the retinol group had significant photodamage improvement over the vehicle at all time points during the study. After 52 weeks, retinol had improved crow's feet fine lines by 44 percent and mottled pigmentation by 84 percent, with over 50 percent of subjects showing +2 improvement in many parameters. Additionally, at week 52, histochemical data confirmed the clinical results, showing increased expression of type I procollagen, hyaluronan, and Ki67 compared to vehicle. The study concluded that a stabilized retinol (0.1 percent) formulation could significantly improve the signs of photoaging, and improvements in photodamage continue with prolonged use. (Reference: https://www.ncbi.nlm.nih.gov/pubmed/25738849 )

A study compared the effects of retinol and retinoic acid on skin structure and expression of skin function-related genes and proteins. It also examined the effect of retinol treatment on skin appearance. The study concluded that topical retinol application significantly affects both the epidermis and dermis' cellular and molecular properties, as shown by skin biopsy and non-invasive imaging analyses. Although the magnitude tends to be smaller, retinol induces similar changes in skin histology and gene and protein expression compared to retinoic acid application. These results were confirmed by the significant facial anti-aging effect observed in the retinol efficacy clinical study. (Reference: http://www.ncbi.nlm.nih.gov/pubmed/26578346  )

Adverse effects

Note from the author of this review: retinoids, such as retinol and tretinoin, have many adverse effects. Retinoids (and vitamin A, retinol) are toxic to the liver, but this is a bigger problem when taken systematically, e.g., orally, such as in acne therapy. Retinoids may also cause skin irritation with redness, burning, itching, and scaling after sun exposure, so the application of the cream should be done only at night, and those taking retinoids should use a sunscreen with high SPF (e.g., more than 50) during exposure to the sun; otherwise, a sunburn may develop. They may also cause skin dryness, so skin moisturizer is required. Moreover, they may cause teratogenesis, so they should not be used by pregnant women, as they may cause birth defects and cause congenital malformations in the fetus. Pregnant women should also avoid excessive vitamin A because of the liver toxicity that may be caused along with birth defects.

People with liver disease, including alcohol-related liver disease, should also avoid retinoids and high amounts of vitamin A that cause hypervitaminosis A due to their damaging effects on the liver (hepatotoxicity), especially if taken systematically (e.g., orally).

(Reference (Retrieved July 21, 2018): https://www.drugs.com/sfx/retin-a-side-effects.html and https://en.wikipedia.org/wiki/Retinol#Side_effects  )

Isotretinoin, retinol, and tretinoin (a retinoid) are used for acne treatment All-trans retinoic acid (ATRA; tretinoin) is also used as a treatment for acute promyelocytic leukemia! Regarding acne, many parents neglect to take their adolescents with moderate to severe acne to a skin doctor for treatment, leaving them with face scars! In women, acne may be a sign of polycystic ovary syndrome (PCOS) that needs a differential diagnosis.

Natural face or eye creams or serums for wrinkles

These may contain panthenol (vitamin B5), pomegranate, rose (it may be wild rose), collagen, hyaluronic acid (alone or with vitamin C and E, as well as flavonoids), argireline®, retinol, and peptides (Oligopeptide-20, Copper Peptide-1, Palmitoyl Pentapeptide-3, and Acetyl Hexapeptide-8).

Copper peptides (e.g., copper tripeptide)

Copper peptides (such as copper tripeptide – 1) are also advertised as a treatment for wrinkles and are used in face & eye creams. However, the author of this review did not find on PubMed any study to prove their effectiveness.

A study investigated the mechanism of copper's role in wound healing or skin aging by regulation of matrix metalloproteinase – 1 (MMP-1) and IL-8 (interleukin – 8) genes. The study concluded that copper facilitates wound healing and skin aging via the induction of MMP-1 expression, with limiting MMP effect at higher concentrations through enhanced IL-8 expression, which favors extracellular matrix deposition. (Reference: http://www.ncbi.nlm.nih.gov/pubmed/20053132 )

Adverse effects

There is also a consideration of the potential side effects of copper, such as the association with Alzheimer’s disease (AD) and the apoptotic effects (associated with programmed cell death).

Copper is known to be a critical factor in Alzheimer's disease (AD) pathogenesis (disease development), as it is involved in amyloid-beta (Aβ) peptide-related toxicity. A study describes that copper dramatically affects Aβ42 aggregation and enhances Aβ42 cytotoxicity, while it shows no significant effects on Aβ40. Moreover, the research authors test the effect of an analog of copper, nickel, on Aβ aggregation and cytotoxicity, finding that nickel also enhances cytotoxicity via Aβ42 nanoscale oligomer formation. These results clarify that the copper-induced Aβ42 nanoscale oligomer formation is the critical process for Aβ neurotoxicity (nerve toxicity) and suggest that disrupting the interactions between copper and Aβ42 peptide to inhibit the nanoscale oligomerization process deserves more attention in Alzheimer's disease (AD) drug development. (Reference: http://www.ncbi.nlm.nih.gov/pubmed/21952557 )

A study assessed the apoptotic (that causes programmed cell death) and genotoxic (causing gene mutations) potential of copper oxide nanoparticles (CuONPs) (50 nm) in the human skin epidermal (HaCaT) cells and its underlying mechanism of cellular toxicity. Significant decreases in cell viability were observed with CuONPs exposure in a dose- and time-dependent manner. Also, they induced a significant reduction in glutathione and induction in lipid peroxidation, catalase, and superoxide dismutase in HaCaT cells. The CuONPs also induced DNA damage that was mediated by oxidative stress. This study investigating the effects of CuONPs in human skin cells has provided valuable insights into the mechanism of potential toxicity induced by CuONPs. (Reference: http://www.ncbi.nlm.nih.gov/pubmed/23667135 )

My comment: the apoptotic (that causes programmed cell death) effects were confirmed on dermal (skin) papilla cells (DPCs).

Other peptides such as palmitoyl oligopeptide-20, palmitoyl pentapeptide-4 και acetyl hexapeptide-8

Other than copper peptides used for wrinkles, peptides include palmitoyl oligopeptide-20, palmitoyl pentapeptide-4, and acetyl hexapeptide-8.

Palmitoyl pentapeptide

The palmitoyl pentapeptide palmitoyl-lysine-threonine-threonine-lysine-serine (pal-KTTKS) is a synthetic material designed as a topical agent to stimulate collagen production and thus provides a skin anti-wrinkle benefit. A 12-week, double-blind, placebo-controlled, split-face, left-right randomized clinical study assessed if pal-KTTKS is effective. Caucasian female subjects (n = 93 subjects, aged 35 – 55) participated. The study assessed two topical products: moisturizer control product vs. the same moisturizer product containing 3 ppm pal-KTTKS. The results showed that Pal-KTTKS was well tolerated by the skin and provided significant improvement vs. placebo control for reducing wrinkles/fine lines by quantitative technical and expert grader image analysis. In self-assessments, subjects also reported significant fine line/wrinkle improvements and noted directional effects for other facial improvement parameters. (Reference: http://www.ncbi.nlm.nih.gov/pubmed/18492182 )

    Synthetic hexapeptides [such as the patented synthetic peptide Argireline ® (acetyl hexapeptide – 3) & the acetyl hexapeptide – 8]

   Synthetic hexapeptides such as the patented synthetic peptide Argireline ® (acetyl hexapeptide – 3) & the acetyl hexapeptide – 8 may also be useful on wrinkles. 

     Argireline® (acetyl hexapeptide – 3)

    Argireline® is a well-known, innovative anti-aging product used in the cosmetic market as an active ingredient in dermal ointment and creams. Argireline prevents the formation of skin lines and wrinkles in a very similar way to the botulinum toxin (Botox), inhibiting neurotransmitter release at the neuromuscular junction! Argireline does not require under-skin muscle injections and is believed to be relatively safe.  However, even though the product manufacturer has provided some toxicity data, there is an evident lack of reliable information about the cytotoxicity of Argireline in the literature.  (Reference: https://www.ncbi.nlm.nih.gov/pubmed/24644551 )

    A study evaluated the safety and efficacy of Argireline ® in the treatment of periorbital (around the eyes) wrinkles in Chinese subjects. Sixty subjects received a randomized therapy of Argireline ® or placebo in a ratio of 3:1. Argireline ® or placebo was applied to their peri-orbital wrinkles twice daily for four weeks. Then evaluations were made for the improvements in wrinkles. The results showed that in the subjective assessment, the total anti-wrinkle efficacy in the Argireline ® group was 48.9 percent, compared with 0 percent in the placebo group. In the objective evaluation, roughness parameters decreased in the Argireline ® group, while no decrease was evident in the placebo group. In conclusion, this study showed that Argireline ® had a significant anti-wrinkle effect in Chinese subjects. (Reference: http://www.ncbi.nlm.nih.gov/pubmed/23417317 )

Adverse effects

A study investigated the antiproliferation effect of an Argireline solution in several concentrations. The influence of Argireline on cellular proliferation was examined against the human embryonic kidney HEK-293 cell line, human neuroblastoma IMR-32 cell line, and human primary skin fibroblasts. The method considered in the study resulted in dose-dependent Argireline anti-proliferation effects. However, the significant cytotoxicity (cell toxicity) of Argireline solution was observed under 18 to 10,000-fold higher concentrations (depending on cells that were examined) in comparison to doxorubicin (a chemotherapy drug). (Reference: https://www.ncbi.nlm.nih.gov/pubmed/24644551 )

LK and AEDG peptides 

A study investigated the influence of LK and AEDG peptides in concentrations 0.05-2.00 ng/ml on organotypic skin cell cultures proliferation in young and old animals. The results showed that these peptides stimulated skin fibroblast proliferation in 29-45 percent of skin cell cultures of young and old rats. This effect was observed in smaller concentration diapason and levels during skin aging in old cell cultures as compared to young cell cultures. (Reference: https://www.ncbi.nlm.nih.gov/pubmed/25946846 )

Botulinum toxin (BTX) (also known as ‘Botox’!)

Botulinum toxin (BTX) is a lethal neurotoxin protein. However, it has been used effectively in cosmetics as an injection for treating facial wrinkles, especially the periorbital (around the eyes), although the results are temporary. A specialist doctor, a plastic surgeon, or a dermatologist (skin doctor) should administer the treatment.

Allantoin

Allantoin is a major metabolic intermediate in most organisms, including animals, plants, and bacteria. It is produced from uric acid, which is a degradation product of purine nucleobases, by urate oxidase (or uricase)

Using planimetric and histological methods, a study assessed the wound healing process profile induced by allantoin incorporated in soft lotion oil/water emulsion. Female Wistar rats (n=60 subjects) were randomly assigned to 3 experimental groups: (C) control group without treatment; (E) group treated with soft lotion O/W emulsion excipients; (EA) group treated with soft lotion O/W emulsion containing allantoin 5 percent. The study showed a histological wound healing profile induced by allantoin in rats and demonstrated that it could improve and fasten the re-establishment of healthy skin. (Reference: http://www.ncbi.nlm.nih.gov/pubmed/20877959 )

Botox (botulinum toxin) injections & surgery

Other methods for face wrinkles include Botox (Botulinum toxin) injections and surgical techniques (from plastic surgeons) such as face lifting.

Other natural treatments

Snail slime!

Some cosmetic companies sell face creams containing snail slime (secretions) that claim they may help people with facial wrinkles.

A 2-center, double-blind, randomized, 14-week study assessed the safety and efficacy of a topical antiphotoaging (skin age from sunlight) product containing secretions of the snail Cryptomphalus aspersa (SCA) for the improvement of facial rhytides (wrinkles). The investigators treated 25 patients with moderate to severe facial photodamage with an emulsion (8 percent SCA), liquid serum (40 percent SCA) on one side of the face, and placebo on the contralateral side for 12 weeks. The study concluded that the daily application of topical products containing secretions of the snail Cryptomphalus aspersa (SCA) proved effective and well-tolerated for improvement in coarse periocular rhytides (wrinkles around the eyes) and fine facial (related to the face) wrinkles. The subjects noted a significant degree of improvement in fine lines at the 8-week time point on the SCA-treated side but did not report a significant difference in the quality of their skin. (Reference: http://www.ncbi.nlm.nih.gov/pubmed/23652894 )

    

    Note: Cornu aspersum (Cryptomphalus aspersa; the old name was Helix aspersa), also known by the common name garden snail, is a species of land snail and it is a terrestrial pulmonate gastropod mollusk that belongs to the family Helicidae (this family includes the most commonly familiar land snails).  


     Plants & herbs

   Although some manufacturers advertise the use of ‘rare species of melons’ from France on face creams for wrinkles, there is a lack of studies on melons and their use for wrinkles.

    Melothria heterophylla (Solena amplexicaulis) 

In a study, Melothria heterophylla was selected for its antioxidant activity and inhibitory effect on Matrix metalloproteinase – 1 (MMP-1) expression in UVA-irradiated human skin fibroblasts. Two compounds (compounds 1 and 2) were isolated. These compounds were found to scavenge radicals and reactive oxygen species (ROS). The study concluded that compounds 1 and 2 significantly inhibited MMP-1 expression at the protein level. Also, these compounds were determined to have potent antioxidant activity. From these results, the authors of this study suggest that these compounds might be useful as a new anti-aging agent for photodamaged (damaged from sun UV beams) skin. Still, the in vitro findings must be verified by in vivo studies. (Reference: http://www.ncbi.nlm.nih.gov/pubmed/16957808 )

     Quercetin

     Quercetin is another supplement used in face creams for wrinkles. However, the published studies on its effectiveness are few.

     In a study, plant phenolic compounds were isolated from a 70 percent aqueous acetone extract of Malus doumeri A. CHEV leaves. var. formosana, a type of Taiwanese indigenous plant, was evaluated for potential application in skin care. A phytochemical investigation of the active fractions resulted in the isolation of seven compounds, of which spectroscopic characterization identified the structures. The study evaluated the isolated phenolic compounds for their free radical-scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and the superoxide radicals, anti-elastase, and for their anti-matrix metalloproteinase-1 (MMP-1) activity in human skin fibroblast cells. Of these compounds, 3-hydroxyphloridzin (2), 3-hydroxyphloretin (6), and quercetin (7) exhibited the strongest DPPH and superoxide radical-scavenging activities. The study results suggest that the extract of Malus doumeri var. formosana containing phenolic compounds could be suitable naturally occurring active constituents for use in anti-aging or cosmetic products.  (Reference: http://www.ncbi.nlm.nih.gov/pubmed/16595910 )

     A study investigated the possible beneficial effects of topical formulations containing quercetin to inhibit UVB irradiation-induced oxidative damage. Quercetin was administered on the hairless mice's dorsal skin using formulation 1 (non-ionic emulsion with high lipid content) and formulation 2 (anionic emulsion with low lipid content). The UVB irradiation induced a dose-dependent increase in the myeloperoxidase (MPO) activity (4-2708 percent) and depletion of reduced glutathione (GSH) (22-68 percent) in the skin of hairless mice after 6h. The study demonstrated the effectiveness of topical formulations containing quercetin to inhibit UVB irradiation-induced skin damage. This data suggest using topical formulations containing quercetin to prevent UVB radiation skin damage. (Reference:  http://www.ncbi.nlm.nih.gov/pubmed/16495072 )

     Argan oil  

     In a study, sixty postmenopausal women consumed butter during the stabilization period. They have randomly divided into two groups for the intervention period: the treatment group of 30 participants received dietary argan oil, the control group of 30 participants received olive oil, and both groups applied cosmetic argan oil in the left volar forearm during a 60-day period. The study concluded that the daily consumption and/or topical application of argan oil have an anti-aging effect on the skin, demonstrated by improved skin elasticity, characterized by increased R-parameters (R2, R5, and R7) and a decrease in RRT. (Reference:  http://www.ncbi.nlm.nih.gov/pubmed/25673976 )

     Vitamin E (tocopherol)

     Vitamin E (tocopherol) is widely advertised and used as an antioxidant in face creams for wrinkles. However, the studies that show its effectiveness are few. 

     Biodynes, a tocotrienol-rich fraction (TRF), and tocopherol have shown anti-aging properties. A study assessed the skin-aging effects of biodynes, TRF, and tocopherol on the stress-induced premature senescence (SIPS) model of human diploid fibroblasts (HDFs) by determining the expression of collagen and MMPs at gene and protein levels. The results showed that biodynes, TRF, and tocopherol upregulated collagen genes and downregulated MMP genes. The findings indicated that biodynes, TRF, and tocopherol effectively enhanced collagen synthesis and inhibited collagen degradation and, therefore, may protect the skin from aging.    (Reference: http://www.ncbi.nlm.nih.gov/pubmed/24396567 )

     A study using both the ascorbate free radical and an EPR spin-trapping system to detect short-lived radicals evaluated the effect of the topically applied antioxidants tocopherol sorbate, alpha-tocopherol, and tocopherol acetate on an ultraviolet radiation-induced free-radical formation. The results showed that tocopherol sorbate significantly decreases the ultraviolet radiation-induced radical flux in the skin. With a chronically exposed mouse model, tocopherol sorbate was substantially more protective against skin photoaging than alpha-tocopherol and tocopherol acetate. These results confirmed ultraviolet radiation-induced free-radical generation in the skin and indicated the utility of tocopherol sorbate as an antioxidant to protect against ultraviolet radiation-induced oxidative damage. (Reference: http://www.ncbi.nlm.nih.gov/pubmed/7706763 )

     Vitamin C (ascorbic acid)

   

    As an antioxidant, vitamin C (ascorbic acid) is widely used in anti-wrinkle face creams.

    A study evaluated by high-frequency ultrasound the cutaneous changes induced by topical use of a vitamin C complex at the facial level. A vitamin C-based solution/Placebo moisturizer cream was applied at the facial level of 60 healthy female subjects according to a predetermined protocol. The study showed that topically applied vitamin C is highly efficient as a rejuvenation therapy, inducing significant collagen synthesis in all age groups with minimal side effects. (Reference: http://www.ncbi.nlm.nih.gov/pubmed/26366101 )

     A study assessed the efficacy and safety of topical 23.8 percent L-ascorbic acid serum on photo-aged skin. Twenty Chinese women with photo-aged skin were enrolled in this split-face study. They were treated with topical L-ascorbic acid serum with iontophoresis on one side of the face once a day for 2 weeks; the other side of the face was spared treatment through participants' self-control. The study concluded that the topical 23.8 percent L-ascorbic acid serum is useful for treating photo-aged skin and does not cause any apparent side effects.  (Reference: http://www.ncbi.nlm.nih.gov/pubmed/22206077 )

Various vitamins (such as biotin (vitamin B7), vitamin A, and provitamin B5), metals (such as iron), and proteins (such as carnitine or peptides that constitute proteins) have been used as a natural treatment of wrinkles, especially on people deficient in these vitamins for various reasons such as in periods of stress, ailment, strenuous job or exercise, school exams, etc. These are used topically or taken systematically (orally), and it is believed that they are helpful for people with wrinkles.

    Coenzyme Q10 (CoQ10)

   Coenzyme Q10 is widely advertised and used as an antioxidant in face creams for wrinkles. However, the studies that show its effectiveness are few. 

    Coenzyme Q10 (CoQ10), an essential compound of cellular bioenergetics, also acts as a potent antioxidant and protects the body against aging. The preparation of a novel proniosomal (PN) gel formulation of CoQ10 employing a systematic design of experiment (DoE) approach is a step ahead in transcending the constraints of the topical delivery. Animal skin was treated with UV radiation, followed by PN gel CoQ10 and conventional CoQ10 in a gel base. The effectiveness of the treatment was evaluated based on biochemical estimation and histopathological studies. By using CoQ10 PN gel formulation, levels of superoxide dismutase (SOD), catalase (CA), glutathione (GSH), and total proteins were restored by 81.3 percent, 72.1 percent, 74.8, and 77.1 percent, respectively to that of the control group. Histopathological studies revealed better protection of skin treated with CoQ10 PN gel than free CoQ10. Prepared PN gel was found not disturbing with the normal histology hence, tolerated by animal skin compared to conventional gel. (Reference: HTTPS://WWW.NCBI.NLM.NIH.GOV/PUBMED/26302815 )

   

     Idebenone (a synthetic analog of coenzyme Q10)

    Idebenone is an antioxidant lower molecular weight analog of coenzyme Q10. In a non-vehicle control study, 0.5 percent and 1.0 percent of idebenone commercial formulations were evaluated in a clinical trial for topical safety and efficacy in photodamaged skin. Forty-one female subjects aged 30-65 with moderate photodamaged skin were randomized to use a blind labeled (either 0.5 percent or 1.0 percent idebenone in otherwise identical lotion bases) skincare preparation twice daily for six weeks. The immunofluorescence staining revealed a decrease in IL-1b, IL-6, and MMP-1 and an increase in collagen I for both concentrations. (Reference: http://www.ncbi.nlm.nih.gov/pubmed/17129261 )

     Note: idebenone has been studied for memory problems, including Alzheimer’s.

Green tea and Ginkgo biloba

Ginkgo biloba is a herb used for memory and circulation problems; however, as it increases circulation, it is believed that it helps wrinkle treatment by assisting the skin's microcirculation.

A study evaluated the effects of cosmetic formulations containing green tea (GT) and/or Ginkgo biloba (GB) extracts through preclinical and clinical studies. For the preclinical research, histological analysis was performed after a five-day period of formulation application on the dorsum of hairless mice. For the clinical research, the formulations were applied on the forearm skin of 48 volunteers and assessed before and after 3 hours and after a 15 and 30 day-period of application. The study concluded that the formulation containing a combination of green tea and Ginkgo biloba extracts effectively improved skin conditions. The effect of formulation FBlend on improving skin elasticity was more pronounced. (Reference: HTTPS://WWW.NCBI.NLM.NIH.GOV/PUBMED/25226010   )

      
    Gotu Kola (Centella asiatica)

    The titrated extract of Centella asiatica (TECA; Gotu kola) is a reconstituted mixture comprising asiatic acid, madecassic acid, asiaticoside, and madecassoside, and is used as a therapeutic agent in wound healing and also as an anti-microbial, anticancer and anti-aging agent. A study investigated the photoprotective role of TECA via microRNA (miRNA) expression profiling analysis. The results suggest that Centella asiatica (TECA; Gotu kola) may serve as a potential natural chemoprotective agent against UVB-mediated damage (from sunlight) in normal human dermal fibroblasts (NHDFs) through changes in the expression of specific miRNAs. (Reference:   http://www.ncbi.nlm.nih.gov/pubmed/22948173 )

     
     Resveratrol

     Resveratrol, a great anti-aging polyphenol

   The oxidative damages induced by a redox imbalance cause age-related changes in cells and tissues. Superoxide dismutase (SOD) enzymes play a pivotal role in the antioxidant system and catalyze superoxide radicals. Since the loss of cytoplasmic SOD (SOD1) resulted in aging-like phenotypes in several types of murine tissue, SOD1 is essential for maintaining tissue homeostasis. Melinjo (Gnetum gnemon) seed extract (MSE) contains trans-resveratrol (RSV) and resveratrol derivatives, including gnetin C, gnemonoside A, and gnemonoside D. MSE intake also exerts no adverse events in human studies. A study investigated the protective effects of MSE on age-related skin pathologies in mice. The results showed that trans-resveratrol (RSV) in Melinjo (Gnetum gnemon) seed extract (MSE) stably suppressed an intrinsic superoxide generation in vivo and in vitro, leading to protecting skin damage. RSV derivative rich Melinjo seed extract (MSE) may be a powerful food for treating age-related skin diseases caused by oxidative damage. (Reference:   http://www.ncbi.nlm.nih.gov/pubmed/26180586 )

     Resveratrol is a plant-derived polyphenol. A study investigated the possible existence of specific binding sites in human skin mediating resveratrol's protective action. The authors used human skin tissue to report specific [(3)H]-resveratrol binding sites mainly located in the epidermis. By acting on particular polyphenol binding sites in the epidermis, the study suggests that resveratrol may be useful for preventing skin disorders associated with aging.   (Reference: http://www.ncbi.nlm.nih.gov/pubmed/20886076 )

Skin aging & herbs

The association between Ayurveda and anti-aging is gaining importance in beauty, health, and wellness. Ayurvedic cosmeceuticals date back to the Indus Valley Civilization. Modern research trends revolve around principles of the anti-aging activity described in Ayurveda: Vayasthapana (age-defying), Varnya (brighten skin glow), Sandhaniya (cell-regeneration), Vranaropana (healing), Tvachya (nurturing), Shothahara (anti-inflammatory), Tvachagnivardhani (strengthening skin metabolism) and Tvagrasayana (retarding aging). Many rasayana plants, such as Emblica officinalis (Amla) and Centella asiatica (Gotu kola), are extensively used (Reference: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3151377 ).

Phytoconstituents are gaining popularity as ingredients in cosmetic formulations as they can protect the skin against exogenous and endogenous harmful agents and help remedy many skin conditions. Exposure of skin to sunlight and other atmospheric conditions causes the production of reactive oxygen species, which can react with DNA, proteins, and fatty acids, causing oxidative damage and impairment of the antioxidant system. Such injuries damage regulation pathways of the skin and lead to photoaging (skin aging from sunlight exposure) and skin cancer development. The effects of aging include wrinkles, roughness, the appearance of fine lines, lack of elasticity, and de- or hyperpigmentation marks. Herbal extracts act on these areas, producing healing, softening, rejuvenating, and sunscreen effects. The authors selected a few photoprotective phytoconstituents, such as curcumin, resveratrol, tea polyphenols, silymarin, quercetin, and ascorbic acid. They discussed the considerations to be undertaken for developing herbal cosmetic formulations that could reduce the occurrence of skin cancer and delay the photoaging process. (Reference: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249896/ ).

The author’s recommended face mask for wrinkles

For face wrinkles, I recommend his ‘patent’ of suffusing the face with a mixture of oils, including rosemary oil, thyme oil, stinging nettle oil, walnut oil, avocado oil, sweet almond oil, rose oil, argan oil (made in Morocco), soybean oil, wheat germ oil, sea buckthorn oil (contains omega 7 fatty acids such as palmitoleic acid), extra – virgin olive oil, evening primrose oil, sesame oil, Chios island mastic (plant resin) oil, and aloe vera oil. The most essential oil in the mixture is virgin olive oil. Buying all these oils is expensive. However, someone may use the oil mixture for many months (e.g., apply it three days weekly). A cheaper solution is to use a mix of 50 percent olive oil and 50 percent vegetable oil (preferably sesame oil or argan oil, but less expensive is soy, sunflower, or corn oil). The oil mixture should be applied on the face for 30 – 60 minutes (sparing the eyes). Then it is advised to apply above (without washing out the skin) a mixture composed of a high-fat (e.g., 10 percent) yogurt, 3 whole eggs, whipped cream (a 200 – 300 ml box; not aerosol) with a high-fat content (e.g., 30 percent), 20 tablespoons of whole-wheat flour, a teacup of 50 percent olive oil and 50 percent of vegetable oil (soybean oil or sunflower or corn oil), and 2 teaspoons of honey. After stirring the mixture with a fork, you may keep it in the fridge to be more solid or apply it to the facial skin for 30 – 60 minutes. You can apply the mixture every other day and, on the weekend, store it in the freezer; the next week, you can thaw it and use it for five more days. That means that the recipe will suffice for nearly two weeks of use. The mixture can also become a cake if baked!

II) Cosmetics for hair loss

Alopecia is hair loss or thinning of hair. It is unbelievable that most people are unaware that the treatment for hair loss already exists and has been used effectively for many years. It is the medication minoxidil that has dramatically improved hair loss treatment. Topical treatment, especially in the foam form, effectively treats hair loss. However, the critical point for its effectiveness is its early use for hair loss prevention when the problem starts, which may even be in adolescence. Another critical issue is poor compliance, as many people do not comply with the proper therapeutic scheme. Some may find minoxidil a bit expensive, but its price is comparable to ‘natural’ lotions that offer minimal or zero effects! Another drug that is used for alopecia (hair loss) is finasteride. Still, it is taken systematically (orally) and should be reserved as a treatment by a specialist skin doctor. The doctors who are experts on hair and scalp problems are called ‘trichologists,’ but it is not a famous specialty, so their number worldwide is still small. I guess the best is in California!

   

Avoid hats!

For preventing wrinkles, you should avoid the sun, while for preventing hair loss, you should avoid wearing a hat all the time, like Americans who wear a baseball or jockey cap not for sun protection but even in the evening because it is trendy!  


The drug Minoxidil

Topical minoxidil as a solution or foam is the best and most effective treatment for alopecia (hair loss). Treatments usually include a 5 percent concentration solution for men and a 2 percent concentration solution for women. Its mechanism comprises potassium channel opening. Initially, it was studied for hypertension! In the US, the FDA approves it. 

Androgenetic alopecia (AGA) is the most common cause of hair loss in men. A new minoxidil formulation with improved cosmetic characteristics (DC0120) was tested for noninferiority vs. a comparator minoxidil product (ALOSTIL^®) stimulating hair growth in men with AGA. Two 10 cm² areas on the scalp of each subject were randomized to receive DC0120, the comparator, or one of their corresponding vehicles, applied twice per day for 16 weeks. Two hundred and twenty subjects were included and randomized, of which 210 completed the study. The study showed that both minoxidil treatments increased non-vellus TAHC compared to vehicle groups at 8 and 16 weeks. No new safety signals were observed. The study concluded that the new minoxidil formulation DC0120 was as safe and effective as a similar marketed minoxidil product for stimulating hair growth in men with androgenetic alopecia (a male autoimmune pattern of hair loss) (AGA). (Reference: https://www.ncbi.nlm.nih.gov/pubmed/29659116  )

A review assessed the published medical and non-medical treatments for male and female androgenetic alopecia (AGA; a male autoimmune pattern of hair loss) using the American College of Physicians evidence assessment methods. The review showed that the medical treatments with the best evidence classification for efficacy and safety for male AGA are oral finasteride and topical minoxidil solution. For female AGA, topical minoxidil solution appears to be the most effective and safe treatment. The medical treatments corresponding to the next level of evidence quality are some commonly used therapeutic non-FDA-approved options, including oral and topical anti-hormonal therapies. Surgical treatment of follicular unit hair transplantation is an option in cases that have failed medical treatment, although there is a high variation in outcomes. The review concluded that the assessment of the evidence quality of current publications indicates that oral finasteride (for men only) and topical minoxidil (for men and women) are the best treatments for androgenetic alopecia (AGA). (Reference: http://www.ncbi.nlm.nih.gov/pubmed/24848508 )

A systematic review & meta-analysis assessed the effects of minoxidil on androgenetic alopecia (AGA; a male autoimmune pattern of hair loss). The results showed that minoxidil is more effective than placebo in promoting total and non-vellus hair growth. A significantly higher proportion of participants in the minoxidil group had greater hair growth than participants in the placebo group, as judged by both investigators and self-reports. Despite significant clinical efficacy, cosmetically acceptable results are present in only a subset of patients. Compliance is considered a significant limiting factor addressed by novel formulations and combinations. (Reference: http://www.ncbi.nlm.nih.gov/pubmed/26380504 )

Adverse effects of minoxidil

Minoxidil has many adverse effects, including skin irritation & allergy, unwanted hair growth elsewhere on the body, temporary hair loss, and worsening hair loss.

Minoxidil may also have antiandrogen effects, as the following study showed (these effects may explain its hair stimulation effects as occurs with finasteride, which is described below and has antiandrogen effects).

Although minoxidil has been used for more than two decades to treat androgenetic alopecia (a male autoimmune pattern of hair loss) (AGA), an androgen-androgen receptor (AR) pathway-dominant disease, its precise mechanism of action remains elusive. The authors hypothesized that minoxidil might influence the androgen receptor (AR) or its downstream signaling. These tests revealed that minoxidil suppressed AR-related functions, decreasing androgen receptor (AR) transcriptional activity in reporter assays, reducing expression of AR targets at the protein level, and suppressing AR-positive LNCaP cell growth. The study's findings provide evidence that minoxidil could be used to treat both cancer and age-related diseases and open a new avenue for applications of minoxidil in treating androgen-AR pathway-related disorders.  (Reference: http://www.ncbi.nlm.nih.gov/pubmed/24742982 )

The drug Finasteride

A systematic review concluded that the assessment of the evidence quality of current publications indicates that oral finasteride (for men only) and topical minoxidil (for men and women) are the best treatments for androgenetic alopecia (AGA, a male autoimmune pattern of hair loss). (Reference: http://www.ncbi.nlm.nih.gov/pubmed/24848508 )

Finasteride is a drug used for benign prostatic hyperplasia (BPH) and hair loss. It is an antiandrogen as it is a type II & III 5-alpha-reductase inhibitor. The enzyme 5α – reductase converts the androgen sex hormone testosterone to the more potent androgen sex hormone dihydrotestosterone (DHT).

The study's authors followed Japanese men with androgenetic alopecia (a male autoimmune male pattern of hair loss) treated with finasteride for five years to evaluate long-term treatment efficacy. Of the 903 men treated with finasteride (1 mg/day), 801 patients were assessed over five years by adjusted global photographic assessment. Although the proportion of improvement was high (99.4 percent), modified global photographic assessment scores after five years of treatment were lower in patients with more advanced diseases as measured by the modified Norwood-Hamilton scale. After separating patients into "sufficient" and "insufficient" efficacy groups according to the modified global photographic assessment score after five years (scores ≥6 and <6, respectively), multivariate analysis showed that independent risk factors of insufficient efficacy were age at the start of treatment of forty years or more and classification on the modified Norwood-Hamilton scale. In contrast, stress at the beginning of therapy was a negative predictor. In conclusion, continuous five-year finasteride treatment improved androgenetic alopecia with sustained effect among Japanese. Younger age and less advanced disease at the start of therapy were the key predictors of higher finasteride efficacy. (Reference: http://www.ncbi.nlm.nih.gov/pubmed/25903108 )

Adverse effects of finasteride

Finasteride is an antiandrogen and may cause sexual dysfunction and mood disorders. It may also increase the risk for high–grade prostate cancer; however, the risk of male breast cancer has not been proven yet. 

FDA notified healthcare professionals that the Warnings and Precautions section of the labels for the 5-alpha-reductase inhibitor (5-ARI) class of drugs had been revised to include new safety information about the increased risk of being diagnosed with a more severe form of prostate cancer (high-grade prostate cancer). 

A retrospective pharmacovigilance disproportionality analysis assessed finasteride for sexual dysfunction (SD) and suicidal ideation (SI) effects.  United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database was assessed. The study concluded that persistent sexual dysfunction (SD) might be a potential risk of low-dose finasteride for androgenic alopecia therapy in young men. This risk might contribute to suicidal ideation (SI). These findings provide a strong hypothesis for pharmaco(=drug)-epidemiologic studies to further examine this association.(Reference: http://www.ncbi.nlm.nih.gov/pubmed/26133534)

Minoxidil plus Finasteride (synergistic effect)

The synergism of combined use between oral finasteride and topical minoxidil has been established in treating androgenetic alopecia (a male autoimmune pattern of hair loss) among men. A study compared the efficacy and safety of a topical solution of 0.25 percent finasteride mixed with 3 percent minoxidil vs. 3 percent minoxidil solution in men with androgenetic alopecia. Forty men aged 18-60 years with androgenetic alopecia were randomized to 24 weeks of treatment with a twice-daily finasteride/minoxidil or minoxidil solution. The primary efficacy endpoint was the change from baseline in hair density and diameter at week 24. The results showed that at week 24, the combined solution of finasteride and minoxidil was significantly superior to minoxidil alone in improved hair density, hair diameter, and global photographic assessment. About 90 percent of patients treated with the combined solution experienced moderate to marked improvement. The mixed solution had minimal effect on plasma dihydrotestosterone levels, with approximately a 5 percent reduction. There were also no systemic adverse events reported by patients in both group. The study concluded that treatment with the topical solution of 0.25 percent finasteride admixed with 3 percent minoxidil was significantly superior to the 3 percent minoxidil solution for promoting hair growth in male androgenetic alopecia and well-tolerated. (Reference: https://www.ncbi.nlm.nih.gov/pubmed/29972712 )

Saw palmetto & beta-sitosterol

Saw palmetto is an herb that resembles the drug finasteride. It is used for benign prostatic hyperplasia (BPH), and some also use it for hair loss. Its mechanism of action is still being investigated. However, antiandrogen effects like finasteride have been described, including the 5α– reductase inhibition (antiandrogen effects). Saw palmetto contains phytosterols (plant sterols) that decrease LDL – (bad) cholesterol levels.

Beta-sitosterol is a plant sterol that inhibits 5α (alpha) – reductase. Thus, it has antiandrogen effects and may help in hair loss. 

My comment: as a plant sterol, beta-sitosterol has been used as an effective way to decrease blood cholesterol and has been added to dairy products such as yogurt, butter, milk, etc. Taken systematically, it may also be a hair loss treatment!

An open-label study assessed the effectiveness of Serenoa repens (Saw palmetto) in treating male androgenetic alopecia (AGA; a male autoimmune pattern of hair loss), by comparing its results with finasteride. The study enrolled 100 male patients with clinically diagnosed mild to moderate AGA. One group received Serenoa repens 320 mg daily for 24 months, while the other received finasteride 1 mg every day for the same period. The results showed that Serenoa repens (Saw palmetto) could improve androgenetic alopecia, while finasteride confirmed its efficacy. The authors also clinically observed that finasteride acts in both the front area and the vertex (the uppermost surface of the head), while Serenoa repens prevalently in the vertex. (Reference: http://www.ncbi.nlm.nih.gov/pubmed/23298508 )

A study assessed botanically derived enzyme 5-alpha-reductase (5AR) inhibitors, specifically the liposterolic extract of Serenoa repens (LSESr; Saw palmetto) and beta-sitosterol, in the treatment of AGA. The study included males between the ages of 23 and 64, in good health, with mild to moderate androgenetic alopecia (AGA; male pattern hair loss). The results of this pilot study showed the effectiveness of naturally occurring enzyme 5-alpha-reductase (5AR) inhibitors against androgenetic alopecia (AGA; male pattern hair loss) for the first time and justified the expansion to more extensive trials. (Reference:  http://www.ncbi.nlm.nih.gov/pubmed/12006122 )

Peptides such as oligopeptide-54, decapeptide-18 and -10, monolaurin-18.

Various peptides have been used for hair loss, and their effectiveness has been studied.

Copper peptides such as copper tripeptide

Copper tripeptide is another substance used for hair loss.

The tripeptide-copper complex, described as a growth factor for various differentiated cells, stimulates the proliferation of dermal fibroblasts and elevates the production of vascular endothelial growth factor but decreases the secretion of transforming growth factor-beta1 by dermal fibroblasts. Dermal papilla cells (DPCs) are specialized fibroblasts essential in hair follicles' morphogenesis and growth. A study assessed the effects of L-alanyl-L-histidyl-L-lysine-Cu2+ (AHK-Cu; a copper tripeptide) on human hair growth ex vivo and cultured dermal papilla cells. The study concluded that AHK-Cu (a copper tripeptide) promotes the growth of human hair follicles, and this stimulatory effect may occur due to stimulation of the proliferation and the preclusion of the apoptosis (programmed cell death) of dermal (skin) papilla cells (DPCs). (Reference:  http://www.ncbi.nlm.nih.gov/pubmed/17703734 )

Adverse effects

There is also a consideration for the potential adverse effects of copper, such as the association with Alzheimer’s disease (AD) and cell apoptosis (programmed cell death). It may also have photodamaging effects (damage from the sunlight) on the hair.

Copper is known to be a critical factor in Alzheimer's disease (AD) pathogenesis (disease development), as it is involved in amyloid-β (Aβ) peptide-related toxicity. The studies mentioned above, in the previous section, referred to wrinkles.

A study assessed whether low levels of redox metals such as copper will accelerate damage to the hair on exposure to UV irradiation and whether this damage can be prevented. The methods used were proteomics to measure the protein damage via protein loss after different periods of exposure and mass spectroscopy methods to identify specific marker peptides specially created by this type of injury. The study demonstrated the role of copper in UV-induced damage to hair and strategies to reduce copper levels in hair using a chelate such as EDDS. (Reference: http://www.ncbi.nlm.nih.gov/pubmed/23962007 )

Ginkgo biloba

This herb is used for memory and circulation problems. However, as it increases circulation, it is believed that it helps hair loss treatment by assisting the microcirculation of the scalp in regenerating the hair follicles. However, there is a lack of studies to prove its effectiveness. The ‘hair cells’ referred to in some studies on Ginkgo biloba are related to the ear (they are the sensory receptors of both the auditory system and the vestibular system in the ears), as this herb is also used for ear problems, including tinnitus.



Shampoos, conditioners, hair masks, and lotions with keratin and/or arginine

Many companies sell shampoos, conditioners, hair masks, and lotions with keratin and/or arginine that are believed to be useful for hair regeneration while they prevent hair loss. These can be purchased from the supermarket and are relatively cheap. I don’t think it is better to take arginine as a dietary supplement when you can buy a cheap conditioner or hair mask with arginine that goes immediately on the scalp. Conditioners and hair masks have the benefit over shampoos that remain longer on the scalp, but you still need to wash them out.   On the other hand, lotions have the advantage of staying longer on the scalp, as they are not washed out immediately.

Vitamins (such as biotin (vitamin B7), vitamins A, C, and E (usually as tocopherol), nicotinamide, vitamin B3, and provitamin B5), metals (such as iron), and proteins (such as carnitine and arginine or peptides (such as biotinyl tripeptide) that constitute proteins) and flavonoids (such as apigenin) and other substances (such as oleanic acid and diguanosine-tetra-phosphate) and herbs (sea buckthorn, thyme, rosemary, wheat, lupin, stinging nettle, honey, chamomile, propolis, Panax ginseng, tea).

Various vitamins (such as biotin (vitamin B7), vitamins A, C, and E (usually as tocopherol), nicotinamide, vitamin B3, and provitamin B5), metals (such as iron), and proteins (such as carnitine and arginine or peptides (such as biotinyl tripeptide) that constitute proteins) have been used as a natural treatment of hair loss, especially on people deficient in these vitamins for various reasons such as in periods of stress, ailment, strenuous job or exercise, school exams, etc. These are used topically (lotion, shampoo, conditioner, hair mask) or taken systematically (orally). These nutrients are believed to be helpful in hair loss.  

Additionally, flavonoids (such as apigenin), herbs (sea buckthorn, thyme, rosemary, wheat, lupin, stinging nettle, honey, chamomile, propolis, Panax ginseng, tea), and other substances (such as oleanic acid and diguanosine-tetra-phosphate) have been used topically (lotion, shampoo, conditioner, hair mask) as hair loss treatment.

Rosemary oil

Rosmarinus officinalis L. is a medicinal plant with diverse activities, including enhancement microcapillary perfusion. A study investigated the clinical efficacy of rosemary oil in treating androgenetic alopecia (AGA; a male autoimmune pattern of hair loss) and compared its effects with minoxidil 2 percent. Patients with AGA were randomly assigned to rosemary oil (n = 50 subjects) or minoxidil 2 percent (n = 50 subjects) for 6 months. After a baseline visit, patients returned to the clinic for efficacy and safety evaluations every 3 months. Each volunteer's standardized professional microphotographic assessment was taken at the initial interview and after 3 and 6 months of the trial. No significant change was observed in the mean hair count at the 3-month endpoint, neither in the rosemary nor the minoxidil group. In contrast, both groups experienced a significant increase in hair count at the 6-month endpoint compared with the baseline and 3-month endpoint. No significant difference was found between the study groups regarding hair count at month 3 or month 6. The frequency of scalp itching at the 3- and 6-month trial points was significantly higher than baseline in both groups (P < .05). Scalp itching was more frequent in the minoxidil group at both assessed endpoints. The findings of the present trial provided evidence concerning the efficacy of rosemary oil in treating androgenetic alopecia (AGA). (Reference: https://www.ncbi.nlm.nih.gov/pubmed/25842469 )

Hair coloring & natural hair dyes

For hair coloring, there are natural hair dyes without PPD (a common cause of allergy), alcohol, lead, ammonia parabens, resorcinol, or other harmful carcinogenic ingredients.  However, they contain hydrogen peroxide, which decolors the hair before applying the dye.

Laser Combs

Special low–level laser combs that use a laser beam of a particular frequency are advertised to stimulate hair growth.

An animal study investigated a low-level laser comb to alleviate the symptoms of androgenetic alopecia (AA; a male autoimmune pattern of hair loss) in a C3H/HeJ mouse model for AA. Fourteen C3H/HeJ mice with induced AA were used in this study. Two were killed to confirm AA through histology. The remaining 12 mice were randomized into two groups; group I received HairMax LaserComb™ (wavelength: 655 nm) for 20 s daily, three times per week for 6 weeks; Group II was treated similarly, except that the laser was turned off (sham-treated). The study concluded that LaserComb™ seems to be a useful and convenient device for treating androgenetic alopecia (AA) in the C3H/HeJ mouse model.  (Reference: http://www.ncbi.nlm.nih.gov/pubmed/21739260 )

A retrospective observational study evaluated the efficacy and safety of low-level laser therapy (LLLT) for androgenetic alopecia (AGA; a male autoimmune pattern of hair loss), either as monotherapy or as concomitant therapy with minoxidil or finasteride, in an office-based setting. In the study, male and female patients with AGA, were treated with the 655 nm-HairMax LaserComb(®), in an office-based setting. Efficacy was assessed with global photographic imaging. The study concluded that low-level laser therapy (LLLT) represents a potentially effective treatment for both male and female androgenetic alopecia (AGA), either as monotherapy or concomitant therapy. Combination treatments with minoxidil, finasteride, and LLLT may act synergistically to enhance hair growth (Reference: http://www.ncbi.nlm.nih.gov/pubmed/25191036  )

Hair transplantation

Surgical treatment of follicular unit hair transplantation by a dermatologist is an effective treatment for hair loss, but it is costly, and a skin doctor performs it.

The author’s natural hair mask recommendation for alopecia (hair loss or thinning of the hair)

For hair loss and generally and for nourishing the hair and stimulation of hair growth, the author of this review recommends suffusing the hair with a mixture of oils, including rosemary oil, thyme oil, stinging nettle oil, walnut oil, avocado oil, sweet almond oil, rose oil, argan oil (made in Morocco), soybean oil, wheat germ oil, sea buckthorn oil (contains omega 7 fatty acids such as palmitoleic acid), extra – virgin olive oil, evening primrose oil, sesame oil, and aloe vera oil. The essential oil in the mixture is virgin olive oil. The cost of buying all these oils is a bit expensive. However, someone may use the oil mixture for months (e.g., you can apply it 3 days weekly). A cheaper solution is to use a mix of 50 percent olive oil and 50 percent vegetable oil (preferably sesame oil or argan oil, but less expensive is soy, sunflower, or corn oil). The oil mixture should be applied on the scalp for 30 – 60 minutes. Then it is advised to apply above it (without washing out the skin) a mixture composed of a high-fat (e.g., 10 percent) yogurt, 3 whole eggs, whipped cream (a 200 – 300 ml box; not aerosol) with a high-fat content (e.g., 30 percent), 20 tablespoons of whole-wheat flour, a teacup of 50 percent olive oil and 50 percent of vegetable oil (soybean oil or sunflower or corn oil), and 2 teaspoons of honey. After stirring the mixture with a fork, keep it in the fridge to be more solid or apply it to the facial skin for 30 – 60 minutes. Then, you can wash your face using tepid water and soap. If you apply the preparation every other day, you can store it in the freezer on the weekend; next week, you can thaw it and use it for five more days. That means the recipe will suffice for nearly two weeks of use. The mixture also becomes a cake if baked!

III) Herbs & dietary supplements used for wrinkles

(With green colors are the herbs & dietary supplements that I consider more important for this issue)

Alpha-lipoic acid

As a topical form, it may benefit people with skin problems, such as wrinkles and blemishes.

Astaxanthin

Two human clinical studies were performed. One was an open-label, non-controlled study involving 30 healthy female subjects for 8 weeks. Significant improvements were observed by combining 6 mg per day of oral supplementation and 2 ml (78.9 μM solution) per day of topical application of astaxanthin. It may suggest that by combining oral supplementation and topical treatment, astaxanthin derived from Haematococcus pluvialis can improve skin condition in all layers, such as the corneocyte layer, epidermis, basal layer, and dermis.

Another was a randomized, double-blind, placebo-controlled study involving 36 healthy male subjects for 6 weeks. Crow's feet wrinkle and elasticity; and transepidermal water loss (TEWL) were improved after 6 mg of astaxanthin (the same as the former study) daily supplementation. Moisture content and sebum oil level at the cheek zone showed strong tendencies for improvement. These results suggest that astaxanthin derived from Haematococcus pluvialis may improve skin conditions in women and men.

Hyaluronic acid

A study evaluated the efficacy of a new topical low molecular nano-hyaluronic acid preparation in treating wrinkles, skin hydration, and skin elasticity in humans. Thirty-three women with an average age of 45.2 were studied for eight weeks to measure the anti-wrinkle efficacy of a new nano-hyaluronic acid. The study showed a statistically significant moisturizing effect of the product range (lotion, serum, and cream, after 2, 4, and 8 weeks of treatment. Measurement of skin roughness showed a significantly finer skin structure after two weeks of treatment, and skin elasticity showed a significant improvement after 2 and 8 weeks of treatment. The study concluded that the new nano-hyaluronic acid clearly demonstrated a substantial benefit in decreasing the depth of wrinkles (up to 40 percent), and skin hydration (up to 96 percent) and skin firmness and elasticity were significantly enhanced (up to 55 percent) at the end of eight weeks.

Hydrolyzed collagen

Idebenone

A synthetic product, similar to coenzyme Q-10.

It is claimed that it has anti-aging properties.

Topical use of vegetable oils (avocado, walnut, sweet almond, rose, argan, sea buckthorn, extra virgin olive, evening primrose, sesame, pomegranate, aloe vera & rosemary).

Argan oil

During menopause, the decrease of estrogenic secretion induces the disruption of skin functioning, thus causing the decline in skin elasticity characteristic of skin aging. A study in postmenopausal (after menopause) women evaluated the effect of daily consumption and/or application of argan oil on skin elasticity. Sixty postmenopausal women consumed butter during the stabilization period and were randomly divided into two groups for the intervention period: the treatment group of thirty participants received dietary argan oil, the control group of 30 participants received olive oil, and both groups applied cosmetic argan oil in the left volar forearm during a 60-day period. The results showed that consumption of argan oil led to a significant increase in the gross elasticity of the skin (R2), the net elasticity of the skin (R5), biological elasticity (R7), and a significant decrease in RRT. The application of argan oil led to a considerable increase in the gross elasticity of the skin (R2), the net elasticity of the skin (R5), biological elasticity (R7), and a significant decrease in RRT. In conclusion, these findings suggest that the daily consumption and/or topical application of argan oil have an anti-aging effect on the skin, demonstrated by improved skin elasticity, characterized by increased R-parameters (R2, R5, and R7) and a decrease of RRT.

IV) Herbs & dietary supplements used for alopecia (hair loss or thinning of hair)

(With green colors are the herbs & dietary supplements that I consider more important for this issue)

Olive oil (topical use)

Topical applications of specific essential oils

Topical use of vegetable oils (avocado, walnut, sweet almond, rose, argan, sea buckthorn, extra virgin olive, evening primrose, sesame, pomegranate, aloe vera & rosemary).

They may help those with skin infections and stimulate new hair growth. Someone can use 3 – 4 drops each of peppermint, rosemary, and sage in 1 tablespoonful of vegetable or olive oil.

Rosemary essential oil & a mixture of essential oils applied topically

In a study of eighty-four people with alopecia areata (a disease in which hair falls out, generally in patches), the results showed that 44 percent of those who massaged their scalps with rosemary and other essential oils (including lavender, thyme, and cedarwood) every day for 7 months experienced significant improvement, compared to those who massaged their scalps without the essential oils.

Saw palmetto & beta-sitosterol

Saw palmetto had been suggested as a potential treatment for male pattern baldness. It contains beta-sitosterol, a plant sterol that decreases cholesterol.

Beta-sitosterol may help in androgenetic alopecia (a male autoimmune pattern of hair loss).

A study tested botanically derived 5-alpha reductase inhibitors, specifically the liposterolic extract of Serenoa repens (saw palmetto) and beta-sitosterol, in the treatment of androgenetic alopecia and showed a highly positive response to treatment – the blinded investigative staff assessment report showed that 60 percent of (6/10) study subjects dosed with the active study formulation were rated as improved at the final visit.

In another study of 34 men and 28 women, topically applied Serenoa Repens (SR) (saw palmetto) extract in lotion and shampoo base for three months led to a 35 percent increase in hair density and a 67 percent increase in sebum reduction assessed by sebometry, pHmetry, hydration studies, and phototrichogram.

Another study showed that adding an extract of 0.5 percent SR to ketoconazole shampoo gave better results than ketoconazole alone.

Topical use of vegetable oils (avocado, walnut, sweet almond, rose, argan, sea buckthorn, extra virgin olive, evening primrose, sesame.

Reference for the above herbs & dietary supplements are my texts on https://herbsanddietarysupplementsdatabase.blogspot.com/ 

Thanks for reading!