Good Essay About Niacinamide In Dermal Therapies
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Introduction: Niacinamide is an amide of niacin. It is the active form of the vitamin. Niacin is converted to niacinamide predominantly in liver. Other body tissues are also capable to amide conversion. Both the forms of vitamin are heterocyclic aromatic compound. They are collectively called Vitamin B3. Yeast, milk, fish, eggs, green vegetables, beans and cereal grains are rich sources of this vitamin. People whose diet is solely based on staple food like corn, are likely to suffer from niacin deficiency. Tryptophan is a substrate for in vivo synthesis of niacin, and this amino acid is deficient in corn. In United States, niacin and niacinamides are added as supplements in flours and breads. A common deficiency disease associated with niacin and niacinamide deficiency is pellagra (webmd.com, 2015). Symptoms of pellagra include: diarrhoea, inflamed mucous membrane, scaly skin, delusions and mental confusions (Nlm.nih.gov,2015). Niacinamide supplementation was found to be effective in treating a myriad of diseases like diabetes, cholera, schizophrenia, drug associated hallucination, Alzheimer’s, cognitive deficiencies, chronic brain syndrome, depression, motion sickness, oedema, headache, indigestion, arthritis. Among skin disorders niacinamide was found effective in treating bullous pemphigoid, granuloma annulare, and inflammatory acne vulgaris (Webmd.com, 2015). The primary function of niacinamide in cells, is to support metabolism. Niacin is used in the synthesis of NADH and NADPH, which have roles to play in all aspects of cell metabolism (Combs, 2012). It was has roles in cell signalling and communication (Gaidarov et al., 2013). The signalling events of niacin are mediated by Erk-1/2 pathways (Gaidarov et al., 2013). Vascular dilation and flushing symptoms associated with niacin application of on the skin is a result of niacin signalling in endothelial cells.
Niacinamide has a pyridine ring with an amide group in position three. Its metabolism within skin is unknown. Nicotinic acid and nicotinamide are active form of the vitamin. Both form possess almost the same activity. Niacin and nicotinic acid are converted to amide form in the tissues. Skin has poor ability to convert niacin to nicotinamide. Purified nicotinamide is an odourless, white, crystalline solid, which easily dissolves in water. It is resistant to heat, light, air and alkali, and thus stable in most cosmetic preparation. Niacinamide a component of NAD and NADP, which are involved in a number of oxidation- reduction reaction of the cell, and participate by transfer of H+ ions. Important metabolic reactions catalysed by NAD and NADP are: glycolysis, TCA cycle, lipid metabolism, glycogen synthesis, glycogen breakdown, fatty acid oxidation, fatty acid synthesis, steroid synthesis and protein metabolism. Niacinamide is rapidly absorbed by the skin. Isoniazid induced pellagra was found to resolve, on topical application of niacinamide. This suggest that, niacinamide was capable of entering the systemic circulation through the skin. Niacinamide taken orally is rapidly cleared from the blood, and distributes itself in high concentration in organs like liver, kidney and adipose tissue. There are no true storage sites for niacinamide/ niacin in the body. Only a small portion of niacinamide is converted to niacin in the skin. No data is available about its metabolism in skin. However studies in rats indicate, that the first phase rapid metabolism and clearance of niacinamide from the body takes place in the liver. The niacin is removed from NAD and NADP by NAD glycohydrolase enzyme of the liver and intestine. The ability of skin to convert niacin to niacinamide is negligible. The catabolic by-products of niacinamide are excreted in the urine, as N-1-methynicotinamide and 4-pyridone or 6-pyridone of N-1- methylnicotinamide. Though diet is the main source of niacin, human body is capable of synthesizing niacin from amino acid tryptophan. Approximately 60 mgs of tryptophan may be required for synthesis of 1 mg of niacin. All cells in the body are capable of synthesizing niacin from tryptophan. (Dcm.com, 2015)
Discuss in detail the mechanism of action of niacinamide on a cellular level:
Niacinamide is the precursor for coenzymes like NADH and NADPH. Both these molecules have an important metabolic role inside the cell. NADPH is vital for conversion of oxidised glutathione to reduced glutathione. Glutathione is an enzyme that has a significant role in removing free radicals from the cell. It converts peroxide into water molecule, by donating its H+ ion, and in the process becomes oxidised to an inactive oxidised form. Oxidised glutathione gains its functioning again, by accepting H+ ion from NADPH. This final reaction is catalysed by the enzyme glutathione reductase (Schoneich & Mozziconacci, 2011). NADPH is also required for the synthesis of fatty acid and complex lipids like ceramide. Malonyl Co A synthase enzyme of fatty acid synthesis pathway uses NADPH as a cofactor (Katiyar & Porter, 1975). NADH is an inhibitor of glycosaminoglycan synthesis. It inhibits both UDP-glucose dehydrogenase and UDP 4’ epimerase activities. Both these enzymes are necessary for the synthesis of glycosaminoglycan (Luca, Speziale, Rindi, Balduini & Castellani, 1976). The above mentioned functions of niacinamide in skin, are important for the maintenance of stratum corneum and strengthening of the skin barrier. Niacinamide can modulate proinflammatory cytokine response and inhibit vascular oxidative stress. It reduces the production of inflammatory cytokine like IL-1, TNF-a and IL-6 from macrophages. It can also inhibit NF-kB activation. These property of niacinamide, makes it an effect anti-inflammatory agent (Zhou et al., 2014). Anti-inflammatory property of niacinamide has proven effective in treating many aging related changes in the skin. It also helps to reduce skin redness. Lately niacinamide was found to be effective in treating skin changes associated with UV damage. It was capable of reducing PGE2 production in keratinocytes that were subjected to stress, by exposure to non-lethal UV radiation (Xu, 2012). It was able to protect the cell from morphological changes, associated with UV exposure (Xu, 2012). These effects could be a result of its ability, to protect cellular metabolism. Niacinamide down regulates the synthesis of MITF, tyrosinase, TRP1, TRP2 and PMEL17; all of which are involved in melanosome synthesis and transport. This property of niacinamide was found useful in reducing hyperpigmentation (Farris, 2013). Though all the mechanistic details of niacinamide’s various function on the skin, still needs to be elucidated; its effectiveness in treating skin conditions was understood from clinical studies.
Identify the skin conditions in which niacinamide is used to treat in dermatological practise:
Of all tissues in the body, skin is extremely sensitive to niacin/ niacinamide deficiency. Dermatitis and scaly skin are common symptoms of niacin deficiency diseases: Pellagra. The symptom can be easily reversed using by niacin/niacinamide supplementation. Nicotinamide when used topically improves skin condition, and is used for treating dry skin, pigmentation, ultra violet induced immunosuppression, wrinkles and sebum production. Topical application was also found to heal algae vulgaris, by benefit of its sebo-supressive, anti-inflammatory and immunosuppressive properties (Rolfe, 2014). Rosacea is a chronic, incurable skin condition that causes red facial skin, flushing, red bumps, and pustules. Niacinamide based moisturiser, applied twice daily for four weeks was effective in improving the symptoms associated with this disease. Niacinamide when applied topically, was found to reduce the progression of nonmelanoma skin cancer. (Rolfe, 2014). There are also reports of its effectiveness in treating bullous pemphigoid, granuloma annulare, and inflammatory acne vulgaris
Discuss the formulation consideration for use of niacinamide to achieve beneficial clinical effects in dermatological practise as determined within research:
Niacin and Niacinamide are used as cosmetics, primary in skin and hair conditioning. Currently there are 30 cosmetic formulations which includes shampoos, hair tonic, skin moisturisers and cleansing formulations that contains niacinamide. Vitamin B3 used in topical skin applications are mainly in the forms of: niacinamide (aka nicotinamide), nicotinic acid and nicotinate esters (Farris, 2013). The concentration of niacinamide varies based on the type of preparation. In preparation made for application in night the concentration is very low as 0.0001%. On the other hand certain hand and body creams have concentrations as high as 3% (Krutmann & Humbert, 2011). However, most common usage range for hand and body creams, lotions, powders and spays are 0.01% and 0.1% for face mask or mud pack (Krutmann & Humbert,2011). These concentration are approved as safe by the Food and drugs control organisation of many countries. Though we know that Niacin/Niacinamide is important for cell metabolism, its mechanism of action in affecting skin, nail and hair health is not completely understood. Skin, hair and nail lesions are noticed in niacin deficiency diseases like Pellagra. However we lack data to understand how niacinamide affects hair and skin growth in normal healthy subjects. Topical applications containing niacinamide, was able to reduce female pattern hair loss. Studies will be required to understand, the effectiveness of oral supplementation over topical application, in preventing hair fall (Krutmann & Humbert, 2011). Topical application of niacinamide on skin, was found to improve texture and reduce pore size. This could be a result of niacinamide’s ability to inhibit sebum production, by reducing free fatty acid and triglyceride synthesis. Sebum block the pores and increases it pore size. Inhibiting sebum production in the skin can help to reduce skin pore size. After four weeks of application of topical niacinamide, there was significant reduction in the sebum production on Caucasian skin (Farris, 2013). Niacinamide also reduces drying of skin and helps to keep it soft, by strengthening the epidermal barrier and preventing transepidermal water loss. It increases the synthesis of lipids (like ceramide) and proteins (like keratin, involurin, filaggrin) that aids in strengthening the epidermal barrier. Niacinamide also exhibits anti-inflammatory properties and inhibits the synthesis of anti-inflammatory cytokines. Niacin is used in antiaging cosmetics, because of its ability to increase collagen synthesis and reduce wrinkling. Niacin along with retinyl propionate inhibits production of glycosaminoglycan in cell culture by 15%. Niacin reduces skin pigmentation by inhibiting transfer of melanosome from melanocyte to keratocytes (Hakozaki et al., 2002). Fairly high concentration of niacin (2-5%) may be required for reducing hyperpigmentation. The other beneficial effect of niacinamide on complexion, is inhibiting skin yellowing. Protein oxidation (Maillard reaction) is an important reason for yellowing of the skin. The anti-oxidant property of NADPH inhibits oxidation by preventing glycation of proteins, which is an important reason for Maillard reaction in cell. Niacinamide also increase blood flow to the skin, causing flush response and warm sensation of skin. This property may be a disadvantage to sensitive skin types and can cause side effects. These above diverse clinical effect of niacinamide were understood from data obtained in double blind, placebo-controlled and left right randomised studies. In these studies topical application of niacinamide reduced fine lines in the skin and reduced wrinkling. The effect was significant after 8-12 weeks of application. Topical niacinamide also reduced sebaceous lipid production, pore size, and improved skin elasticity; thus reducing all three signs of aging seen in skin. Niacinamide containing cosmetics formulation have challenges like, hydrolysis of niacinamide to nicotinic acid. Unlike niacinamide, nicotinic acid causes vascular dilation of skin blood vessel, resulting in a flushing reaction. This effect is noticed even at concentrations less than 0.01%. This symptom is often aggregated in cold and dry environmental conditions. Reducing the formulation pH to 5-7 and using highly pure niacinamide was able to reduce hydrolysis significantly. Long chain esters of nicotinate were resistant to hydrolysis (Baumann & Baumann, 2009).
Niacinamide dose as high as 5% are generally well tolerated by most individuals. In rare circumstances milk skin irritation is observed. Nicotinic acid form of Vitamin B3 is capable of causing vasodilation at small doses much lower than 1%. Nicotinic acid causes irritation and skin reddening. Niacin and niacinamide being water soluble, are easily absorbed through skin, blood and intestine. Within minutes of absorption into blood they distributes in all body tissue. The highest concentration of niacinamide is found in liver, kidney and adipose tissue. The chief by products of niacinamide catabolism: N1 methy nicotinamide and Ni-methy-4 –pyridone-3 carboxamide are excreted in urine. Though niacin and niacinamide are non-toxic, of the two niacinamide can cause more severe side effects than niacin. However dermal formulation of up to 20% was tolerated by guinea pigs and 5% caused marginal skin irritation in rabbits. Niacinamide formulation was negative for mutagenic effect, when tested using Ames test. Likewise it was also negative for chromosomal aberration test, in Chinese hamster ovary cells. Though no data is available on the carcinogenic property of niacin; niacinamide can potentiate tumour induced by established carcinogen. Niacinamide, when taken in combination with streptozoticin or heliotrine was able to induce pancreatic tumour. However this study does not hold any relevance to its effect on skin. No reports are available on reproductive toxicity caused by this molecules. As a whole, niacin and niacinamide are non-toxic at levels, used in cosmetic preparations. (Andersen, 2005)
Conclusion: Niacinamide has a myriad of dermatological benefits and is used commonly in cosmetic formulation to treat a number of skin condition. It will be a cost effect and friendly way of improving ones skin appearance. Though a complete mechanistic understanding of it action may be lacking, clinical proof of effectiveness has been found in different studies. However we may need data from clinical studies to demonstrate its effect as a formulation on different skin disorder. These studies should be based on proper design and be statistically powered, so as to give clear recommendation about its use in diseases. In the future, one can expect to come across more skin care benefits of niacinamide and this may broaden its clinical utility.
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