New Developments In Understanding Of Sensitive Skin

Sensitive skin is a condition of subjective cutaneous hyperreactivity to environmental factors. Subjects experiencing this condition report exaggerated reactions when their skin is in contact with cosmetics, soaps, and sunscreens and they often report worsening after exposure to dry and cold climates.

Recent findings support the connection between skin microbiota and sensitive skin. Neurohormones diffuse in sweat and epidermis leading skin bacterial microflora to be largely exposed to these host factors. Bacteria can sense a multitude of neurohormones. Substance P (SP) is stimulating the virulence of Bacillus and Staphylococci. The action of SP is highly specific with a threshold below the nanometer level. In a recent study of the mycobiome of sensitive skin was more phylogenetically diverse than that of non-sensitive skin. Lactobacillus and Mucor racemosus were more abundant on sensitive skin than nonsensitive skin, whereas Malassezia restricta was less abundant. Both skin microbiome and mycobiome varied according to the perceived skin sensitivities of the subjects.

Sensitive skin is not limited to the face and the scalp is an area frequently involved: sensitive scalp showed disrupted barrier function, abnormal sebum amount and composition, as well as the perturbed microbiome, which might be the direct cause. The role of microbiome and mycobiome in sensitive skin needs more investigation as well as the possible neurogenic alterations. A complete understanding of this peculiar syndrome may lead to the development of new and more effective pharmacologic and cosmetic treatments.

Bibliography

Misery, Laurent. 2023. “Sensitive Skin Testing.” In Handbook of Cosmetics Science and Technology, by Elsa Jungman, Kazutami Sakamoto, Howard I. Maibach Frank Dreher, 182-189. Boca Raton, London, New York: CRC Press.

Baby Care Products For Skin And Hair

The primary care products that come in contact with baby skin are diapers and cosmetics. Baby cosmetics can be mainly subdivided in two groups, namely cleansing and protecting cosmetics. Recently there is an increase in baby care products that contain natural ingredients or fewer ingredients, however non-all-natural products like certain plant extracts, are recommended to be used on skin. Certain ingredients like perfumes, could lead to skin reactions and should be avoided in baby products, unless considered safe for use on baby. Other ingredients, like preservatives make sense in products where microorganisms can be a risk, like in aqueous based products.

When formulating products there are several factors that need to be considered and it is recommended to work together with experts like toxicologists and microbiologists to ensure the product is safe to use on baby skin. Some ingredients may also be prohibited or restricted in certain countries and experts need to be consulted to ensure that the product is allowed to be marketed and sold in that country.

Hygiene Products: Diapers

The most appropriate strategy for diaper rash is prophylaxis, including keeping the skin clean and dry. Introduction of superabsorbent polymers is used to turn urine into gel. These are absorbent particles that can absorb huge amounts of liquid and therefore help keep the diapers thin but highly absorbent.

Cleansing Cosmetics

Surfactants and Soaps:

Bathing a baby for 5-7 minutes in lukewarm water (35-36°C) usually is sufficient. Better is to use so-called secondary tensides, including nonionics and amphoterics, or mild anionics such as sulfosuccinates, isethionates, and protein fatty acids condensates.

The use of bath foam is not suitable for babies because of its high content of primary tensides producing excessive foam. Parents often think that foam is important for its cleansing properties but foam has no cleansing function, and the ingredients required to produce a sufficient amount of stable foam are often quite irritating and not suitable to be used in baby shampoo, e.g., alkyl sulfates, and alkyl ether sulfates.

Emulsions and Oils:

For cleansing of the baby and in particular the diaper zone, liquid cleansers based on oil-in-water (o/w) emulsions are often used, especially when water and washcloth are not well tolerated by the baby’s skin.

When a baby is prone to contact dermatitis, it is advised to screen the ingredients list because those tissues often contain high concentrations of preservatives, necessary to prevent microbiological contamination of the tissues.

Baby Wipes

Over the last two decades disposable baby wipes have been developed as an alternative to traditional cleansing methods. Wipes consist of a nonwoven carrier material soaked with an emulsion-type, watery or oily lotion. Cleansing studies confirmed that high-quality baby wipes are suitable for daily cleansing of the diaper area, of healthy babies as well as of babies with comprised, irritated skin, on newborn infants and on atopic and premature populations. A cleansing baby wipes with sufficient pH buffering capacity offers an opportunity to stabilize skin pH at physiologic levels and thus help to overcome the potentially detrimental effects of an elevated skin pH in the diaper area.

Protecting Cosmetics

Emollients/Lotions

In good skin care of diaper zone, the application of emollients plays an important role, and the application of a cream layer can create an effective protective barrier. Protective emollients like petrolatum for the nappy zone are preventive or protect the skin against aggressions from urine, feces, and their interactions. Zinc Oxide (ZnO) is an often-used component in diaper rash protection products but may be considered a cosmetic or drug depending on the country. Allantoin, alpha-bisabolol, Aloe vera extract and silicones can be added to improve water resistance.

Powder

Talc powders are not often applied anymore in the diaper area. They absorb moisture, decrease maceration and help prevent irritation of the baby skin. Talc is susceptible to contamination with microorganisms and needs sterilization.

Bibliography

Susanna Brink, M. O. (2023). Baby Care Products. In E. J. Frank Dreher, Handbook of Cosmetic Science and Technology (pp. 339-340). Boca Raton, FL: CRC Press.

Safety Considerations For Baby Care Products

To bring safe baby cosmetics on the market, risk assessment is a key priority and often includes a broadly recognized iterative four-step quantitative exposure-based risk assessment process (US National Academy of Sciences, WHO and the European Union’s Society Scientific Committee on Consumer Safety and Bureau of Indian Standards IS 4011:2018.

The potential impact of skin irritation on dermal absorption should be taken into consideration during baby cosmetic product development.

A distinction should be made between intact, healthy skin and the potentially damaged skin of the nappy zone for which risk factors exist, which are not present for the rest of the body.

The increased prevalence of allergic contact dermatitis in children has prompted scrutiny of products marketed for neonates and children for the presence of sanitisers.

Criteria

During the development of baby products, a number of criteria should be taken into consideration:

• High quality of raw materials in terms of purity, stability, and microbiology via appropriate Certificate of Analysis (CoA).
• Skin Irritation, which is dose-dependent, can be controlled by avoiding well-known irritative ingredients and/or reducing the concentration or frequency of application.
• The presence of sanitizing molecules such as perfume ingredients, even when IFRA (International Fragrance Association) – tested and/or excluding the 26 allergens taken up in regulations, should be avoided if they are not found to be safe.
• The product information file of baby cosmetics, safety data of all ingredients and the finished product, together with a dedicated risk assessment, carried out by a safety assessor, should be present. It should be indicated what specific measures have been taken for baby skin.
• Special attention should be given to the concentration of (i) reactive substances (ii) promotional additives, ‘natural’ and ‘exotic’ ingredients, complex mixtures, plant extracts and animal-derived ingredients or any ingredient from a questionable, impure source; (iii) potential allergens, penetration enhancers, aggressive organic solvents, highly detersive or foaming agents, and antiseptics in particular in daily use products; and (iv) concentrations of preservatives.
• Good practice is: (i) to protect unsaturated lipids from oxidative reactions by adding anti-oxidants; (ii) to adjust and buffer the pH of the final product to skin-friendly pH between 4.5 and 6; (iii) to add chelating or sequestering agents to prevent heavy metal precipitation and protect the preservative system; and (iv) to use known protective skin barrier ingredients.

Dermal Absorption

Dermal absorption data is compound-dependent, varying molecular weight, hydrophobicity
| hydrophilicity, structure, etc., and frequently determined using adult skin.

• The surface area | body weight ratio is 2.3-fold higher in newborns than in adults decreasing to 1.8-fold at 6 and 12 months, respectively. Application of the same amount of product on a similar body surface of baby versus adult could result in higher blood and tissue concentrations in the newborn.
• Pharmacokinetic parameters differ widely between babies and adults and result in reduced clearance and/or a longer half-life of bioavailable substances, thus increasing the potential risk for adverse reactions in babies. Concerning the total body water content, it is known that infants have a higher water content (80-90%) compared to those of adults, which steadily decreases to 55-60%

Another pharmacokinetic difference is a decreased protein binding capacity which can be linked to lower concentrations of glycoproteins in the plasma of infants.

Full-term neonates, tend to show a three to nine times longer pharmacokinetic half-life than adults.

• The SC thickness is reported to be the rate limiting part for percutaneous penetration and thus dermal absorption. The SC is thinner in baby versus adult skin, as measured by confocal laser scanning microscopy, and needs to be considered. The path that molecules have to follow to penetrate the SC layer is potentially shorter.

Importantly, the SC’s barrier is functional at birth and matures for many key skin characteristics (skin pH) in the first few months after birth.

• In use conditions of topical products also play a role. Cosmetic skin care products often are applied onto large body surfaces, e.g., cleansing lotions, sunscreens, etc., increasing not only the potential risk for local effects but also dermal absorption and potential systemic toxicity. This factor is considered in exposure-based risk assessments.
• The Diaper Area and non-diapered regions are indistinguishable at birth but show differential behavior over the first 14 days, with the diapered region having a higher pH and increased hydration. Innovative hygiene absorbent and baby care products, however, provide an increasingly good skin compatibility profile, making the frequency and severity of DD decline.
• Other important factors for dermal absorption are SC hydration and skin pH. For instance, differences in skin pH change the ionization grade of molecules and will influence dermal absorption.

Bibliography

Susanna Brink, M. O. (2023). Baby Care Products. In E. J. Frank Dreher, Handbook of Cosmetic Science and Technology (pp. 339-340). Boca Raton, FL: CRC Press.

Sensitive Skin Testing

(Patel 2021) (Misery 2023)

The evaluation of sensitive skin is useful for assessing the effectiveness of certain products. The “International Forum for the Study of Itch (IFSI) defined sensitive skin as follows: “A syndrome defined by the occurrence of unpleasant sensations (stinging, burning, pain, pruritus, and tingling sensations) in response to stimuli that normally should not provoke such sensations. These unpleasant sensations cannot be explained by lesions attributable to any skin disease. The skin can appear normal or be accompanied by erythema. Sensitive skin can affect all body locations, especially the face.

In a meta-analysis, cosmetics and physical (variations in temperature, cold, heat, wind, sun, air, conditioning, wet hair and dry hair), chemical (water and pollution) or psychological (emotional) factors are associated with sensitive skin. The most important factors are cosmetics, air conditioning, heat, and water).

The global prevalence of “Sensitive Skin” is approximately 50% with variations among some countries.

According to the high frequency of sensitive skin, a single pathophysiological mechanism is debatable. However, a growing body of data supports the hypothesis that sensitive skin is a neuropathic disorder.

Reactivity Tests​

• Stinging Test

The famous lactic acid stinging test (LAST) of Frosch and Kligman is the first standardized test. It consists of the application of 0.5 mL of 10% (or 5%) lactic acid to the nasolabial fold with subsequent assessment of the severity of the subjective symptoms. Erythema is evaluated. Control is provided by the application of a saline solution to the other fold. This test is very commonly used and is very useful for follow-up. (Maheshvari N Patel n.d.)

• Capsaicin Test

A 0.075% emulsion of capsaicin is applied. Similar to the LAST, it could have been controversial since involving the use of a subjective individual pain scale as well and it induced too painful sensations in very sensitive skin subjects.

Additional Tests

The aim of other tests is to evaluate skin properties which can be modified in subjects with sensitive skin but are not directly related to sensitive skin. Hence, the measurement of structural or physiological cutaneous changes after the application of topical irritants can be performed: Trans Epidermal Water Loss (TWEL), cutaneous pH, and epidermal thickness, measured by ultrasonography, optical microscopy, or confocal microscopy, as well as skin penetrability, assessed with UV light, can be studied parameters. Recently, the use of confocal Raman microspectroscopy was proposed to analyze the molecular composition of stratum corneum and consequently the modifications of the skin barrier in sensitive skin. All these tests are commonly used in studies on sensitive skin, but they do not measure skin hypersensitivity.

Questionnaires

• Sensitive Scale

*Sensitive scale (SS-10) is a 10-item scale. Correlation with the dry skin type, higher age, female gender, fair phototypes, and the Dermatology Quality of Life Index (DLQI). DLQI is a tool to evaluate the quality of life in patients with skin disorders.

Skin Irritation

*Important to be completed by the Patient.

Using a vertical line, indicate the symptoms felt during the past 3 days on the horizontal line (0=absence of irritation, 10 = intolerable irritation)

Skin Condition Felt

• Tingling
• Burning
• Sensations of heat
• Tautness
• Itching
• Pain
• General discomfort
• Hot Flashes

Visible skin condition

• Redness

• 3S Questionnaire

The total score can be obtained by multiplying score severity of abnormal sensations by the number of these sensations. The 3S questionnaire allowed discrimination between subjects with slightly sensitive, sensitive and very sensitive scalp. Itching and prickling are the most frequent symptoms. The 3S questionnaire is a convenient and effective tool for investigating the severity and symptomatology of the sensitive scalp.

• BoSS Questionnaire

The BoSS questionnaire is designed to evaluate all these aspects in patients with sensitive skin. This questionnaire was developed using standardized methods for creating and validating quality-of-life questionnaires, consisting of three phases: a design phase, a development phase, and a validation phase.

Conclusion

A large number of techniques for sensitive skin testing suggests that the authors may try to find a technique for the diagnosis of sensitive skin. In any case, all these subjective and objective tools for sensitive skin testing can be used in comparative studies, especially those that evaluate the efficacy and/or safety of cosmetics and cosmeceuticals.

Bibliography

• Patel, Maheshvari, Gajjar T, Patel N, et al. 2021. “Enhanced efficacy of radiant skin serum in subjects with moderate to severe dry and sensitive skin.” Journal of Dermatology and Cosmetology (MedCrave) Volume 5 (Issue 1): 6-11.
• Misery, Laurent. 2023. “Sensitive Skin Testing.” In Handbook of Cosmetics Science and Technology, by Elsa Jungman, Kazutami Sakamoto, Howard I. Maibach Frank Dreher, 182-189. Boca Raton, London, New York: CRC Press.
• Maheshvari N Patel, Apeksha Merja, Nayan K Patel. n.d. “Standardization and Validation Study for Methods Used for Patch Testing.” Inventi Journals (P) Ltd (Inventi Rapid Clinical Research) 2022 (1): 1-4.

Fundamental of Real-World Evidence Studies

The healthcare industry has been relying on traditional research approaches for a long time, but the information gained from these methods often needs to be expanded in scope.

Real-world evidence studies have the potential to provide new insights into clinical interventions and patient outcomes, giving us a clearer understanding of what works best in different scenarios. Read on to find out why This type of research is essential for making informed decisions in the healthcare sector.

There are several benefits of conducting Real-World Evidence (RWE) studies. RWE can provide insights complementary to traditional clinical trials and help generate new hypotheses about the safety and efficacy of treatments. RWE studies can also be conducted at a fraction of the cost and time of clinical trials, making them an attractive option for drug developers.

Challenges of RWE Studies

There are many challenges associated with conducting real-world evidence studies. First, it can be difficult to identify and enroll appropriate study participants. Second, data collected in the real world is often of lower quality than data collected in controlled clinical trials. It can make it difficult to draw reliable conclusions from real-world evidence studies. Third, real-world evidence studies are often conducted on small samples of patients, which can limit their statistical power and generalizability. Finally, the results of real-world evidence studies can be confounded by numerous factors, such as patients’ baseline characteristics, concomitant medications, and health status at the time of data collection.

Types of RWE Studies

• There are three types of RWE studies: observational, interventional, and hybrid.
• Observational studies are conducted using data already collected, such as from patient registries or electronic health records. These studies can be retrospective (looking back at past data) or prospective (collecting new data).
• Interventional studies involve actively intervening in the care of patients to collect data. These studies can be randomized controlled trials (RCTs) or non-randomized studies.
• Hybrid studies combine elements of both observational and interventional designs. For example, a hybrid study might use data from a registry but also include a component where patients are actively followed over time.

How to Design a Successful RWE Study

There are a few key things to keep in mind when designing a Real-World Evidence (RWE) study:

1. Define your study population and target disease or condition. It will help you determine what data sources to use and how to select your study subjects best.
2. Create a robust data collection plan. It should include specifying which data sources you will use, how you will collect the data, and how you will clean and prepare the data for analysis.
3. Develop clear hypotheses and objectives. Your RWE study should answer specific questions about the effectiveness of treatments or interventions in the real world.
4. Plan for statistical analysis and power calculation. It will ensure that your RWE study is powered to detect meaningful treatment effects.
5. Write a detailed protocol for your RWE study. The document should outline all study aspects, from eligibility criteria to primary and secondary outcomes.
6. Work with experienced partners. Conducting an RWE study can be complex, so it is important to partner with professional organizations or individuals who can help you design and implement the study successfully.

Conclusion

Real-world evidence studies provide invaluable insights into the effectiveness of treatments and therapies in real-world settings. They are an important part of healthcare decision-making, as they can inform decisions that lead to improved patient outcomes. We hope The article has helped you understand the importance of conducting RWE studies and how they can be used effectively in clinical practice. With their help, health professionals can better serve their patients by providing the best possible care based on reliable data.

Ceramide and its metabolites (sphingosine, 4-hydroxy-dihydro sphingosine (phytosphingosine), sphingosine-1-phosphate (S1P) phytosphingosine-1-phosphate and ceramide-1-phosphate (C1P) are lipid mediators that modulate cellular function.

Ceramides and structural pseudo ceramides have been formulated in skin care products and medicine to treat xerosis, psoriasis, atopic dermatitis (AD). Topically applied ceramide, with appropriate chemical formulation, forms stable liquid crystal and bilayer structures, improving permeability barrier integrity on the skin surface. Ceramide may be incorporated into lamellar bilayer structures to enhance barrier integrity in the stratum corneum. It is noted that as changes in ceramide species occur in AD and psoriasis, ceramide species uses for topical agents must be carefully considered. Acylceramide is a ceramide species essential for forming a competent barrier. A suitable selection (and amount) of ceramide is required for the preparation of an effective topical formula. Topically applied ceramide can penetrate into nucleated layers of the epidermis, in particular in barrier-compromised skin. Absorbed ceramide is hydrolyzed to a sphingoid base and FA, which are utilized in endogenous ceramide synthesis.

Oral glycosylceramide and sphingomyelin derived from plants and milk are used (as nutraceuticals) to improve skin moisture and the epidermal permeability barrier. Some oral sphingolipids are hydrolyzed by digestive enzymes and enzymes derived from intestinal microbes and absorbed through the intestinal membrane. Sphingolipids could affect gut immunity. Absorbed sphingolipids are transferred to the liver where they are further metabolized and circulated to peripheral tissues, including skin.

Source: (Uchida)

Clinically Proven” Claim – Scientific Indication

Scientific indications are usually supported with clinical data from relevant human studies that have likely undergone some scientific assessment or scrutiny. Due to this quantifiable scientific research undertaken into their mode of action and/or health benefit, this evidence type is appropriate to support efficacy for your listed medicines/products.
The claim ‘clinically proven’ has become very in demand with marketers of both therapeutic and cosmetic products. This is likely due to the fact that this claim may provide consumers with greater confidence in their choice of products.
In reality, despite the fact that ‘what’ has been clinically proven is not often disclosed, stating that the product is clinically proven suggests that there are proven benefits in using these products, which is enough to influence some consumers to choose these products over others. This is because common consumers might understand a product as having better efficacy, higher safety, or more reliable results.
The word ‘clinical’ refers to the fact that the product has undergone one or more clinical trials, which are clinical studies conducted by a qualified research team in a controlled, scientific unbiased manner. The power of the scientific method is that one can be certain any results obtained are not due to external or uncontrolled factors, and if documented properly, such an experiment is repeatable for anyone wishing to independently verify the results.
The word ‘proven’ means that in the clinical trial(s), the results obtained have been demonstrated to be statistically significant. This means that one can be fairly confident that the results of the product and a test comparator were not obtained due to random variance (chance), or other extraneous factors.
For complementary medicines, the TGA (Australian Government) has some guidance on the use of this term, on their website stating that “…These terms are not acceptable unless supported unequivocally by robustly designed, published peer-reviewed clinical trial(s) conducted on the actual medicine being advertised, or an identical formulation and dose (as a minimum)”. For cosmetic products, the lack of guidelines for the use of claims such as clinically proven might have contributed to some common misconceptions.
The use of the term ‘clinically proven’ in scientific indication infers a level of certainty in the implied health benefits associated with the listed medicines/products in that it has been clinically trialled and proven to be effective. These terms are not acceptable unless supported unequivocally by robustly designed, published peer-reviewed clinical trial(s) conducted on the actual medicine/products being advertised, or an identical formulation and dose (as a minimum). The use of the terms ‘clinical’, ‘clinically’, and ‘scientifically’ coupled with ‘trialled’ or ‘tested’ implies a higher level of certainty associated with the health benefit of your medicine/product and unless matched by well-designed series of clinical studies on your specific medicine/product, may mislead consumers about the effectiveness of your medicine/product.
You must compare your indication with the quoted health benefit in your evidence identified from scientific sources. Your indication will refer to the same clinically significant study outcomes as that reported in the clinical study.
In selecting your scientific indication you should:

• ensure that the medicine’s/product’s therapeutic benefit is demonstrated by the clinical study outcomes
• ensure that any claims you make from your medicine/product imply only the same level of certainty in clinical effectiveness as that reported in clinical studies, for example ‘clinically proven to…’ compared to ‘may assist to…’

Source: (Administration, 2019)

Sunscreen – Complete Sun Protection Strategy

Recurrent exposure of the skin to the sun could result in short-term as well as long-term changes in the structure of the skin. In short-term effects, repeated exposure leads to erythema, whereas repeated exposure in the long term could cause irreversible loss of skin elasticity and the development of melanomas and non-melanomas. Photoprotective agents like sunblocks or sunscreens prevent and reduce the damaging effects of ultraviolet (UV) light.

There are two significant ways that sun exposure can damage your skin health: ultraviolet A (UVA) radiation, which speeds up the aging process in your skin, and ultraviolet B (UVB) radiation, which burns your skin cells. The UV rays from the sun can reach your skin not just when you are outside but even when you are inside your home or car through the windows.

The skin has its natural defense mechanisms to protect it from UV radiation at a certain level. But, it’s insufficient to shield your skin cells from excessive sun exposure, which can result in long-term skin concerns such as age spots, wrinkles, pigmentation, sagging, skin, roughness, darkening, and others.Hence, it is essential to use Sunscreen daily, which acts as a barrier on your skin against sunlight.

Why to use Sunscreen?

The use of sunscreens for protection against the damaging effects of sun rays has been on the rise for years. They have been widely used for their photo protective properties, including the prevention of photocarcinogenesisand photo aging, as well as for the management of photodermatoses. Regular daily use of SPF 15 sunscreen can reduce your risk of developing squamous cell carcinoma (SCC) by about 40 percent, and lower your melanoma risk by 50 percent.

5 W’s and H of Sunscreen:

Who Should Use: Everyone Under the Sun!

Why to Use: Reduce your risk of skin damage and skin cancer!

When to Use:Every day! 30 minutes prior to going outdoors. Reapply every two hours even in winter.

Where to Use: All exposed Skin!

What to Use:Broad spectrum SPF 15 or higher; SPF 30 or higher for a day outdoors!

How to Use:One ounce to the entire body for each application!

**Protected Skin is always in**

Significance of Biotin (Vitamin B) – Supplement for Women with Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common reproductive abnormalities, affecting 5% of the population of reproductive-aged women, is a multifaceted metabolic disease linked with insulin resistance (IR). Women with PCOS produce higher-than-normal amounts of male hormones (Androgens) in the body leading to multiple problems. The exact cause is unknown, but this hormone imbalance causes their body to skip menstrual periods and makes it harder for them to get pregnant. Genetic, Environmental factors; especially nowadays poor diet, and a sedentary lifestyle are the main reasons for PCOD in women. Every 1 in 10 Indian women suffers from PCOD. However, still women are not aware of PCOS/PCOD. It is vital that every woman should know the symptoms so that they can be identified, and treatment can be sought immediately.

Some of the common symptoms involved in PCOS are as follows. In PCOS the arrested follicles (egg sacs) give a typical appearance on ultrasound. The name polycystic ovaries arise from this appearance of the ovaries though these are not cysts but ‘follicles arrested in growth’. Most women with PCOS have insulin resistance meaning that the body’s cells do not respond to insulin in abnormal manner.

Women with PCOS are also in the risk group of developing type 2 diabetes, which makes them more sensitive to insulin. This is why metformin is often used in the treatment of PCOS. Unfortunately,this medicine has an influence on the reduction in vitamin B12 levels after just a few months of intake and is accompanied by an increase in the concentration of homocysteine. Moreover, the inability to get pregnant and random stillbirth in women with PCOS may also be a consequence of the clinical deficiency of B12. In addition, in patients with hyperhomocysteinemia, stillbirth was observed more frequently than in women with correct homocysteine concentration. The researchers have a hypothesis those vitamins soluble in water that hasantioxidant properties and participate in metabolic transformations as regulators may be supplemented together with a reduction diet, thus being beneficial in the treatment of PCOS.

Biotin Helps to Reduce Insulin Resistance: Insulin resistance, inability to utilize insulin hormone is thought to be the main cause of PCOS. A properly balanced reduction diet withreduced GI improves the supply of vitamins in women with PCOS.Biotin (or vitamin B7) is one of the B vitamins.It is also an essential co-factor for a number of important metabolicreactions. For example, it helps the liver and pancreas to manage blood sugar level. Studies have also indicated that biotin or a group of vitamin B is supportive of nervous system health and it may promote healthy Blood fat metabolism.

Benefits of Biotin Supplements:
It is well known that large percentage of women who have polycystic ovarian syndrome also have (IGT) impaired Glucose tolerance. IGT is a pre-diabetic state of disturbed blood sugar that is associated with insulin resistance and increased risk of cardiovascular disease. In future it may also increase in developing higher risk Diabetes. Biotin appears to improve glucose tolerance in women suffering from PCOS. Women with PCOS frequently have unhealthy elevations of cholesterol or triglycerides. High doses of biotin reduce triglycerides as well as a “bad” form for cholesterol. The researchers concluded that pharmacological doses of biotin decrease hypertriglyceridemia. The triglyceride-lowering effect of biotin suggests that biotin could be used in the treatment of hypertriglyceridemia. Water-soluble vitamins do not require special proteins to aid absorption into the bloodstream and are able to move freely throughout the blood and body cells. Excess amounts are secreted in the urine, preventing a toxic build-up. Vitamin B like: Vitamins B2, B3, B5, and B6 are also very useful for controlling obesity in PCOS by the following ways:

• Vitamin B2: Processes fat, sugar, and protein into energy. It is also known as riboflavin.

• Vitamin B3: A component of the glucose tolerance factor which is released every time blood sugar rises, to help keep levels in balance. It is also known as niacin.
• Vitamin B5: This isessential for fat metabolism. It is also known as pantothenic acid.
• Vitamin B6: Maintains hormone balance. Balanced hormones are key to maintaining a healthy body weight.

Lastly, folate and vitamin B12 treatments are shown to improve insulin resistance in patients with metabolic syndrome. So, women with polycystic ovary syndrome should be aware of biotin (Vitamin B) supplements.

ACNE VULGARIS

Acne vulgaris (AV) is a globally occurring inflammatory skin disease manifesting in the pilosebaceous unit of human skin in the form of comedones, papules, and pustules that negatively affect self-esteem and work productivity. The etiopathogenesis of AV is complex, multifactorial, and not fully understood yet. The Cutibacterium acnes bacteria infestation, abnormal keratinization, and excessive lipid production are the main pillars of this disease. The higher colonization of C. acnes observed in inflammatory papules was believed, for decades, to be the main causative factor of AV. C. acnes, under normal aerobic conditions, act as a commensal to the skin, while oxygen deprivation triggers its virulency switching to a pathogenic behavior. C. acnestrapped inside anaerobic comedones environment release lipases with strong proinflammatory and chemoattractant activities that activate the local immune system resulting in inflammation.

Pilosebaceous unit governing cutaneous lipids level is called “the brain in the skin”due to its rich innervation among other skin appendages and its ability to synthetize by sebocytes and other follicular structures of a plethora of neuromediators. These neuromediators, both synthetized denovo and/or released from nerve fibres, regulate cutaneous steroidogenesis, androgen synthesis, and immune functions. The hyperproliferation and hyperactivity of sebocytes in the sebaceous gland during Acne Vulgaris result in excessive sebum production leading to comedones formation.

The nerve growth factor (NGF) plays crucial functions in human skin that are linked to tissue repair and regeneration by enabling reinnervation followed by accelerated cell migration and proliferation. The significantly higher expression of NGF was observed in inflammatory acne lesions, compared to healthy controls. It is proposed that NGF thus may be involved in impaired keratinocytes proliferation, neurogenic inflammation, and pain, all the hallmarks of acne. The cutaneous endocannabinoid system (ECS) regulates cell growth and differentiation, sebum production, and immune functions. The two main ECS representatives, anandamide (AEA) and 2-arachidonoylglycerol are produced by human sebocytes and modulate sebum production in receptor type-dependent fashion. Both ECS and Phytocannabinoids (plant-derived) have been shown to have a strong anti-acne activity that includes the normalization of impaired keratinocytes proliferation, attenuation of inflammatory responses, and homeostasis of SG lipogenesis.

Interestingly, cannabinoids reduce arachidonic acid-induced “acne-like” lipogenesis and facilitate the ‘beneficial’ triglycerides production with anti-inflammatory and microbiome-normalizing properties.

Acetylcholine (ACh) released from autonomic nerves or synthetized by skin cells acting via nicotinic receptor promote infundibular epithelial hyperplasia and follicular plugging leading to comedones formation during Acne Vulgaris.

**Source : (Cezary Skobowiat)**