Skin, Hair, and Nail Health
Collagen peptides. Preclinical and clinical evidence has demonstrated that oral intake of collagen peptides reduces wrinkles and improves skin moisture, elasticity, and overall condition, and may help protect against photoaging (Proksch, Schunck 2014; Proksch, Segger 2014; Pei 2008; Pyun 2012; Okawa 2012).
In a double-blind placebo-controlled study in 69 adult women, oral ingestion of a specific formulation of bioactive collagen peptides resulted in significant improvement in skin elasticity. A skin moisturizing effect was also observed in some elderly women. The skin benefits of oral collagen can be long-lasting, particularly in women over age 50 (Proksch, Segger 2014).
In another double-blind placebo-controlled study, in 114 women, the same orally administered preparation of bioactive collagen peptides reduced eye wrinkle volume. Collagen and elastin synthesis in the skin of the treatment group increased 65% and almost 18%, respectively, compared with the placebo group (Proksch, Schunck 2014).
Collagen is also a critical component of hair, contributing to its strength and growth. In fact, hair follicles produce certain types of collagen in greater amounts than are present in skin. And age-related hair thinning and loss appears to be related to a loss of collagen (Katsuoka 1988; AAS 2016; Hamers 2016).
Collagen peptides provide amino acids from which the body can make keratin. Early studies found that consumption of gelatin, a form of hydrolyzed collagen, for three months resulted in nails that had been soft, peeling, and easily broken returning to a normal, healthy appearance. A similar effect was observed in the treatment of brittle nails using gelatin (Schwimmer 1957; Rosenberg 1957; CPCE 2016; Purdue University 2016).
Solubilized keratin. Keratin is a major structural protein in skin, hair, and nails (Miller 1999; Fujikawa 2012; Chamcheu 2011). A novel formulation, Cynatine HNS, has been shown to deliver a highly bioavailable solubilized form of keratin to the skin. In a randomized controlled trial in 50 women, oral ingestion of Cynatine HNS containing 500 mg of solubilized keratin plus vitamins and minerals significantly improved various aspects of skin appearance including skin moisture, elasticity, and smoothness. Also, the depth of wrinkles was significantly reduced compared with baseline and placebo (Beer 2013).
Cynatine HNS has also been shown to significantly improve the condition of hair and nails. In a randomized clinical trial, women who took Cynatine HNS for 90 days had significantly less hair loss compared with the placebo group. Overall hair quality including shininess and brightness improved substantially in the Cynatine HNS group. Also, more women in the Cynatine HNS group reported having hard and robust nails, and fewer in this group had broken and roughened nails (Beer 2014).
Polypodium leucotomos extract. Polypodium leucotomos (P. leucotomos) extract is derived from a tropical fern plant native to Central and South America. Accumulating evidence indicates oral supplementation of P. leucotomos extract provides potent protection against skin photoaging, suggesting it may also have a role in skin cancer prevention (El-Haj 2015). P. leucotomos has also been studied as a treatment for several skin conditions exacerbated by sun exposure including psoriasis, atopic dermatitis, and vitiligo (Winkelmann 2015; Nestor 2015; Bosch 2015; Choudhry 2014).
P. leucotomos extract is a systemic protective agent with an excellent safety profile that may be useful in the prevention of skin cancer. P. leucotomos inhibits generation of reactive oxygen radicals, enhances the body’s own defenses against oxidative stress, reduces UV light-induced DNA mutations, and helps repair sun-induced damage (El-Haj 2015).
Other mechanisms by which P. leucotomos protects against sun damage include anti-inflammatory and immunomodulating effects (Bosch 2015). P. leucotomos also directly inhibits metalloproteinases—enzymes that degrade collagen and elastin—and increases production of tissue inhibitors of metalloproteinases (Saito 1998; Skjot-Arkil 2012; Philips 2009).
Nicotinamide. Nicotinamide—a form of vitamin B3—has been successfully used orally as a safe treatment for a variety of inflammatory skin conditions including acne and rosacea (Niren 2006; Wang 2015). Nicotinamide also appears to be effective in the prevention of skin cancers (Chen 2015; Yiasemides 2009).
In a randomized controlled trial for skin cancer chemoprevention, 12 months of oral supplementation with nicotinamide in high-risk patients yielded significant benefits. Treatment with nicotinamide resulted in a 23% lower rate of new non-melanoma skin cancers and an 11‒20% reduction in incidence of the precancerous lesion actinic keratosis compared with the placebo group (Chen 2015).
In a placebo-controlled trial in healthy volunteers, doses of either 500 or 1500 mg of nicotinamide, administered for 1 week, significantly reduced immunosuppression induced by UV radiation from sunlight (Yiasemides 2009).
Nicotinamide is the precursor of nicotinamide adenine dinucleotide (NAD+), a compound required for energy (ATP) production. UV radiation suppresses DNA repair by depleting cellular energy. Nicotinamide appears to block damage from UV light through mechanisms that involve cellular energy metabolism and DNA repair. By increasing cellular NAD+, nicotinamide combats the decline in cellular energy and DNA repair associated with UV exposure. In rodent models, nicotinamide has prevented UV light-induced cancer (Chen 2015; Yiasemides 2009; Surjana 2012).
Red orange extract. Red orange extract, derived from a mixture of three red orange varieties (Citrus sinensis varieties: Moro, Tarocco, Sanguinello), is rich in cyanidin 3-glycosides—compounds with free radical scavenging properties (Saewan 2015; Delazar 2010). In a study in cultured human skin cells, red orange extract was shown to inhibit production of malondialdehyde—a marker of lipid oxidation (Morini 2000).
Through its ability to inhibit oxidation, red orange extract protects against photoaging. In a study in healthy volunteers, supplementation with 100 mg red orange extract daily for 15 days significantly decreased the degree of skin redness induced by UV radiation (Puglia 2014). In another study, supplementation with 100 mg red orange extract twice daily for 15 days increased protection against UVB-induced skin damage in 18 healthy women. Specifically, skin reddening in response to a specific dose of UVB radiation decreased by about 35% (Bonina 2016).
Phytoceramides. Ceramides are an essential component of the lipid-rich protective layer within the epidermis. Although present in other tissues, ceramides are especially concentrated in the skin where they help maintain normal skin hydration and barrier function. It is well established that low ceramide levels are an important causative factor in diseases of the skin, and it has been suggested that age-related skin dysfunction could also be a result of ceramide deficiency (Rabionet 2014; Di Marzio 2008; Choi 2005). Ceramide concentrations decrease with age and exposure to UV radiation, as from sunlight (Jensen 2005; Bak 2011).
In a randomized trial, 51 women aged 20‒63 years with dry skin were given either 350 mg of a non-GMO wheat extract containing ceramides or placebo for three months. In the ceramide group, a significant increase in skin hydration and an improvement in clinical signs of dryness were observed at the end of 3 months (Guillou 2011).
Vitamin D. Insufficient vitamin D levels have been linked in epidemiologic studies to cardiovascular disease, diabetes, autoimmune disease, neurologic disorders, some cancers, Alzheimer disease, and increased overall mortality (Sage 2010; Clemente-Postigo 2015; Lu'o'ng 2013). Apart from its role in the production of vitamin D, the skin is also a target tissue for vitamin D. In its active form as calcitriol, vitamin D contributes to healthy skin cell renewal and repair, and supports the skin’s immune system (Mostafa 2015; Reichrath 2012; Drake 2011).
Vitamin D deficiency is an epidemic in North America and throughout the world (Palacios 2014; Hagenau 2009). With more frequent sunscreen use and less sun exposure, the skin’s ability to manufacture vitamin D is compromised, making supplemental intake advisable (Holick 2008; Sage 2010).
Biotin. Biotin is a B vitamin shown to improve nail health. In a controlled clinical trial, a 25% increase in nail thickness was demonstrated in patients with brittle nails who were given biotin supplements (Colombo 1990). In another study, 91% of patients with brittle nails who were given 2.5 mg biotin daily for several months showed a clear benefit with firmer and harder nails (Floersheim 1989).
Hair loss is a symptom of biotin deficiency. Patients with alopecia areata, a severe type of hair loss, may require higher-than-normal biotin intake. In one study, children with this condition were treated with the corticosteroid, clobetasol propionate, alone or in combination with biotin and zinc supplementation. After one year of treatment, 33% of those in the zinc and biotin group had complete regrowth of hair, compared with none treated with corticosteroids alone (Camacho 1999; Higdon 2015a).
Silicon. Silicon is an essential trace mineral that plays a critical role in connective tissue health and is believed to factor into the structural integrity of hair, nails, and skin (Martin 2013). It is involved in the synthesis and stabilization of collagen. Collagen concentrations are decreased in silicon-deficient animals (Carlisle 1986; Jugdaohsingh 2007; Seaborn 2002; Seaborn 1993). Brittle nails may respond to supplementation with silicon (Scheinfeld 2007).
Zinc. Zinc is an essential mineral for healthy skin and hair: it stabilizes cell membranes, is necessary for proper wound healing, and is concentrated in hair follicles. Six percent of the body’s zinc is present in the skin (Angelo 2013).
In multiple clinical trials, zinc has been used successfully to treat alopecia, an immune-mediated type of hair loss. These trials have used months to years of zinc treatment. In one of these studies, dry scaly skin also resolved with zinc treatment (Sonnichsen 1984; Wolowa 1978; Slonim 1992; Ead 1981; Camacho 1999).
Pantothenic acid. Also known as vitamin B5, pantothenic acid is an essential nutrient in the diet and is important to wound healing. In the form calcium D-pantothenate, vitamin B5 increased healing in a preclinical wound-repair model. In a laboratory model, pantothenic acid deficiency inhibited skin keratinocyte proliferation (Higdon 2015b).
Mice that are deficient in pantothenic acid have been shown to develop gray fur and skin irritation, which resolved upon vitamin B5 supplementation (Higdon 2015b).
Omega-3 fatty acids. Omega-3 fatty acids help protect skin against the damaging effects of UV light. Results from preclinical and clinical trials indicate omega-3 fatty acids have both photoprotective and anti-skin-aging effects (Pilkington 2013; Kim 2006; Kim 2005; Angelo 2012).
In a controlled clinical trial, an omega-3 fatty acid supplement rich in eicosapentaenoic acid (EPA) was found to protect against immunosuppression induced by solar-simulated UV radiation in human skin. Supplementation with fish oil rich in omega-3 fats modifies the fatty acid composition of cell membranes by displacing the omega-6 fatty acid arachidonic acid. This leads to a decline in levels of arachidonic acid-derived prostaglandins—cell-signaling molecules that can intensify the inflammation and immunosuppression generated following UV exposure (Surette 2008; Angelo 2012; James 2000; Pilkington 2013).
Lycopene. Lycopene, which is abundant in tomatoes and tomato-based products, can powerfully reduce oxidative stress in skin (Evans 2010). This property may also confer protection against UV light-induced damage(Schagen 2012; Pandel 2013). In a controlled clinical trial, subjects were given either a drink containing 5.7 mg of lycopene, along with several other tomato-derived antioxidants, or placebo for 26 days. At the end of the trial, blood levels of the inflammatory mediator tumor necrosis factor-alpha were over 34% lower in the group that consumed the tomato-based drink (Riso 2006).
In a randomized controlled trial, 20 women ingested 16 mg of tomato-based lycopene daily for 12 weeks. After being exposed to UV radiation, the lycopene-supplemented group was substantially protected against skin reddening compared with the control group. Researchers concluded that lycopene effectively protected the skin from acute and potentially long-term photodamage (Rizwan 2011).
Resveratrol. Resveratrol is a natural compound found in several plants and foodstuffs such as grapes, peanuts, berries, red wine, and Japanese knotweed. In laboratory studies, resveratrol has been demonstrated to effectively neutralize free radicals, inhibit oxidation of low-density lipoprotein, and suppress inflammation (Higdon 2015c).
Resveratrol holds promise as a safe and effective agent against a wide variety of skin conditions, including skin aging and skin cancers (Ndiaye 2011). In a study in tumor-susceptible mice, oral resveratrol markedly suppressed progression of malignant tumors induced by UVB irradiation. Resveratrol also markedly inhibited the malignant conversion of benign papillomas (skin tags) to squamous cell carcinomas (Kim, Back 2011).
In another study, resveratrol reduced tumor growth and metastasis in a mouse model of melanoma. In the same investigation, resveratrol effectively reduced the invasiveness and migration of cultured mouse melanoma cells (Bhattacharya 2011). These results suggest resveratrol may have potential as a treatment for melanoma.
Green tea polyphenols. Green tea polyphenols have been shown to protect against sunburn, immunosuppression, and skin aging caused by UV radiation (Yusuf 2007). In a placebo-controlled trial in 60 women with healthy skin, participants who consumed a beverage with green tea polyphenols had less UV-induced skin redness and better overall skin characteristics. Specific skin variables that improved in the treatment group included elasticity, roughness, scaling, density, and hydration. The ability of plant polyphenols to absorb UV light may account for their UV protective effects (Heinrich 2011).
Heat exposure (eg, from UV radiation) causes damage to the skin’s structural framework by boosting production of collagen-degrading matrix metalloproteinases, resulting in premature skin aging. In a study in human skin fibroblasts, epigallocatechin-3-gallate (EGCG)—the major polyphenolic compound in green tea—markedly inhibited heat shock-induced production of matrix metalloproteinase-1. These results suggest EGCG might be useful in the prevention and treatment of thermal skin aging (Kim 2013).
Hyaluronic acid. Hyaluronic acid, a natural component of many tissues, is a large polysaccharide that efficiently binds water molecules. Hyaluronic acid plays an important role in keeping the skin properly moisturized (Sudha 2014). Hyaluronic acid injections are a popular dermal filler, helping correct cosmetic facial changes associated with aging (Franca Wanick 2016; Brandt 2008). Topically applied hyaluronic acid has been shown to improve skin hydration and elasticity while also significantly reducing wrinkle depth (Pavicic 2011).
In a test conducted by Rutgers University scientists, skin cells treated with a specially modified hyaluronic acid formulation (Hylasome) retained six times more moisture compared with cells treated with regular hyaluronic acid. Hylasome was also shown to suppress oxidative stress four times more effectively than an unmodified hyaluronic acid preparation, suggesting an additional mechanism by which the likelihood of skin damage and wrinkles may be reduced (Vantage 2016).
Matrixyl synthe’6. Matrixyl synthe’6 is a novel tripeptide that promotes the synthesis of six key components of the skin’s structural framework, or matrix: collagen types I, III, and IV, hyaluronic acid, fibronectin, and laminin (Sederma 2016).
In a two-month clinical trial, Matrixyl synthe’6 noticeably decreased wrinkle volume and depth. Forehead and crow’s feet wrinkles were especially smoothed (Sederma 2016).
Topical vitamin C. Vitamin C is a powerful free radical scavenger that also plays an essential role in collagen synthesis. Since skin concentrations of vitamin C decrease with age, restoring levels directly in the skin may reduce facial wrinkles and improve the appearance of photoaged skin. In fact, topical application of vitamin C increases concentrations of the vitamin in the skin 20‒40 times more effectively than oral supplementation. Multiple clinical trials using topical vitamin C have shown this treatment’s ability to improve subjective and objective appearance of photoaged facial skin (Sauermann 2004; Rhie 2001; Traikovich 1999; Humbert 2003; Fitzpatrick 2002; Burke 2004).
In a 12-week placebo-controlled trial in over 20 volunteers, topical vitamin C significantly reduced fine lines and wrinkles in aged skin. Oxidative stress in the skin was also substantially reduced (Raschke 2004). In another randomized trial performed over six months, topical vitamin C cream decreased deep furrows and improved the appearance of photodamaged skin compared with the control (Humbert 2003).
Additional Topical Support
Melatonin. Regulation of the body’s sleep-wake cycle is in part dependent upon the hormone melatonin. The pineal gland in the brain normally releases melatonin in the evenings in preparation for sleep. Up until the last few decades, melatonin was thought to be primarily isolated to pineal synthesis and function narrowly in the regulation of circadian rhythms. But more recently, melatonin has been observed at sites far removed from the pineal gland, including bile fluid, bone marrow, ovaries, white blood cells, and skin (Fischer 2008).
As with its sites of synthesis and actions, the biological activity of melatonin has come into greater light recently. For example, melatonin is now recognized as a potent antioxidant capable not only of neutralizing free radicals directly, but also stimulating other endogenous antioxidant defense systems. In fact, some researchers have employed the term melatonergic antioxidative system when describing these biochemical interactions (Fischer 2008).
Melatonin exerts a broad range of activity in the skin, which has been shown to express melatonin receptors and is another site of melatonin synthesis outside the pineal gland. Studies have shown that melatonin protects against UV-induced skin reddening and DNA damage, increases levels of glutathione (a powerful endogenous antioxidant), and suppresses growth of carcinoma and melanoma skin cancers (Fischer 2008).
In a randomized double-blind trial, topically applied melatonin was shown to protect against UV irradiation of the skin. The effect was dose-dependent and was enhanced when the melatonin was combined with alpha-tocopherol and vitamin C. The melatonin formula was applied 30 minutes before the skin was exposed to UV radiation (Dreher 1998).
DHEA. Dehydroepiandrosterone (DHEA) is an adrenal hormone involved in many physiological functions; it is also a precursor to more potent androgens such as testosterone. DHEA levels decline with age, and this decline has been associated with several health conditions such as depression, atherosclerosis, osteoporosis, frailty, and sexual dysfunction (Samaras 2015; Shin 2005).
Topical DHEA application has been shown to exert anti-aging effects in the skin. In a 13-week trial that enrolled 75 postmenopausal women, topical DHEA application led to increases in levels of proteins involved in collagen synthesis. The investigators concluded that “…topical DHEA could be used as an efficient and physiological anti-ageing skin agent” (El-Alfy 2010). In another clinical trial, a 1% DHEA topical formulation applied for four months improved several subjective measures of skin health (Nouveau 2008).
In a trial in which subjects applied a 5% DHEA formulation 3 times weekly for four weeks, levels and expression of the collagen precursor procollagen alpha 1 increased. This study also found that the topical DHEA applications decreased expression of matrix metalloproteinase-1, and increased expression of transforming growth factor-beta 1 and tissue growth factor messenger RNA (Shin 2005).
DMAE. DMAE (2-dimethylaminoethanol) is an analog of the B vitamin choline and a precursor of the neurotransmitter acetylcholine. In a randomized clinical study, topical DMAE gel applied to the face for 16 weeks safely and effectively reduced forehead lines and wrinkles around the eyes. Lip shape and fullness, as well as overall skin appearance, also improved with DMAE gel (Grossman 2005).
Vegetal filling spheres. Vegetal filling spheres, composed of a plant-based biopolymer, help smooth wrinkled skin by promoting hydration. These tiny spheres penetrate the skin surface where they swell up and fill in wrinkles and lines (BASF 2014).
Salicylic acid. Salicylic acid is a safe and effective peeling agent used to treat various skin conditions including acne, freckles, and liver spots (Arif 2015; Mammone 2006). It has anti-inflammatory properties and has been shown in a preclinical trial to protect skin against sun damage (Arif 2015).
Pichia-fermented resveratrol. Topical resveratrol has been shown to have anti-inflammatory and anti-aging effects (Farris 2013; Puizina-Ivic 2010). In a mouse model of skin cancer, topical resveratrol inhibited the development of tumors (Jang 1997).
Scientists have now developed a more potent topical preparation of resveratrol that is fermented by pichia pastoris yeast. In a placebo-controlled trial, facial treatment with pichia-fermented resveratrol resulted in marked improvements in skin hydration, tone, and texture as well as an improvement in the appearance of wrinkles (Metabiotics 2009).
Botanimoist AMS apple saccharides. Botanimoist AMS “Apple Moisturizing Saccharide” is extracted from dried apples and has been shown to help moisturize the skin. In a placebo-controlled human trial, a single topical application of Botanimoist AMS increased skin hydration by 89% in 30 minutes. After six hours, skin hydration remained 33% higher than controls (Botanigenics 2016).
Snow algae. Found primarily in polar and mountain regions around the world, snow algae are microorganisms that possess anti-aging properties. Snow algae extract has been shown to activate two master “switches” that extend lifespan: the Klotho gene for longevity and the energy sensor AMPK (adenosine monophosphate-activated protein kinase) (Lukes 2014; Snow-Algae 2014a; Snow-Algae 2014b).
Topically applied snow algae may enhance skin appearance and function. In a clinical trial, snow algae powder strengthened skin barrier function, increased skin hydration, and reduced wrinkles. This study took place during winter, a time when cold can increase stress on and water loss from skin (Snow-Algae 2014c).
Alpine rose stem cell extract. The epidermis (skin surface) undergoes a renewal process approximately every two months (Koster 2009). This significant ability of the skin to renew itself relies on a reservoir of epidermal stem cells (Bickenbach 2006). These epidermal stem cells contribute to repair and healing of skin injury, restoring the integrity and functions of the skin (Morasso 2005; Zouboulis 2008; Charruyer 2011; Margadant 2010).
The Alpine rose (Rhododendron ferrugineum) flourishes in the Swiss Alps and the Pyrenees where it endures harsh environmental stresses such as extreme cold and dryness and searing UV rays (Louis 2010; Peng 2008). An ingredient based on stem cells from Alpine rose leaves has been shown to protect epidermal stem cells from UV stress. In an experimental study, epidermal stem cells treated with Alpine rose stem cells were better able to maintain their integrity and were protected from UV-induced stress (PhytoCellTec 2010).
In a clinical trial, treatment of facial skin with Alpine rose stem cell extract, in participants exposed to extreme environmental conditions in the European Alps, significantly improved skin appearance. Wrinkles were less visible in 45% of treated subjects, water loss from skin was reduced by 39%, and decreased redness and irritation was noticed by 54% of subjects (PhytoCellTec 2010).
Palmitoyl dipeptide-5. Palmitoyl dipeptide-5 is a novel peptide that stimulates collagen synthesis in the dermal-epidermal junction, an area of tissue that joins the outer layer of skin (epidermis) with the layer underneath (dermis). In one trial, a topical mixture containing palmitoyl dipeptide-5 was shown to significantly increase skin firmness, tonicity, and suppleness after two months (Centerchem 2016).
Palmitoyl tripeptide-5. Palmitoyl tripeptide-5 is a peptide shown to activate transforming growth factor beta, a protein that boosts collagen synthesis (Lijnen 2002). In a three-month study in 37 women with signs of skin aging, treatment with a topical formula containing palmitoyl tripeptide-5 demonstrated both immediate (within minutes) and long-term improvements in the appearance of fine and coarse wrinkles (Trookman 2009).
Similarly, in a 12-week study, a serum containing palmitoyl tripeptide-5 produced significant reductions in fine and coarse wrinkles in women with facial photodamage. Skin texture, tone, and radiance were improved as well (Sonti 2013).
Acetyl tetrapeptide-2. Acetyl tetrapeptide-2 is a peptide shown to significantly improve elastin synthesis in human skin fibroblasts. In a clinical study in volunteers aged 50‒60 with saggy facial skin, treatment with acetyl tetrapeptide-2 resulted in visibly firmer facial skin. It also increased the formation of type I collagen by 47% (Lipotec 2013).
Disclaimer and Safety Information
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