CLINICAL STUDIES ON THE FOLLOWING INGREDIENTS:
Alpha Lipoic Acid
alpha-Lipoic acid increases energy expenditure by enhancing adenosine monophosphate-activated protein kinase-peroxisome proliferator-activated receptor-gamma coactivator-1alpha signaling in the skeletal muscle of aged mice
Skeletal muscle mitochondrial dysfunction is associated with aging and diabetes, which decreases respiratory capacity and increases reactive oxygen species. Lipoic acid (LA) possesses antioxidative and antidiabetic properties. Metabolic action of LA is mediated by activation of adenosine monophosphate-activated protein kinase (AMPK), a cellular energy sensor that can regulate peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha), a master regulator of mitochondrial biogenesis. We hypothesized that LA improves energy metabolism and mitochondrial biogenesis by enhancing AMPK-PGC-1alpha signaling in the skeletal muscle of aged mice. C57BL/6 mice (24 months old, male) were supplemented with or without alpha-LA (0.75% in drinking water) for 1 month. In addition, metabolic action and cellular signaling of LA were studied in cultured mouse myoblastoma C2C12 cells. Lipoic acid supplementation improved body composition, glucose tolerance, and energy expenditure in the aged mice. Lipoic acid increased skeletal muscle mitochondrial biogenesis with increased phosphorylation of AMPK and messenger RNA expression of PGC-1alpha and glucose transporter-4. Besides body fat mass, LA decreased lean mass and attenuated phosphorylation of mammalian target of rapamycin (mTOR) signaling in the skeletal muscle. In cultured C2C12 cells, LA increased glucose uptake and palmitate beta-oxidation, but decreased protein synthesis, which was associated with increased phosphorylation of AMPK and expression of PGC-1alpha and glucose transporter-4, and attenuated phosphorylation of mTOR and p70S6 kinase. We conclude that LA improves skeletal muscle energy metabolism in the aged mouse possibly through enhancing AMPK-PGC-1alpha-mediated mitochondrial biogenesis and function. Moreover, LA increases lean mass loss possibly by suppressing protein synthesis in the skeletal muscle by down-regulating the mTOR signaling pathway. Thus, LA may be a promising supplement for treatment of obesity and/or insulin resistance in older patients.
Source: Wang Y, Li X, Guo Y, Chan L, Guan X. “alpha-Lipoic acid increases energy expenditure by enhancing adenosine monophosphate-activated protein kinase-peroxisome proliferator-activated receptor-gamma coactivator-1alpha signaling in the skeletal muscle of aged mice.” Metabolism (2010) ;59(7):967-76.
Topical 5% alpha lipoic acid cream in the treatment of cutaneous rhytids
Background: Topical 5% alpha lipoic acid cream has been reported to improve the appearance of facial lines associated with photoaging.
Objective: The purpose of this study was to determine the efficacy of 5% alpha lipoic acid cream in the treatment of photodamaged skin.
Methods: Alpha lipoic acid was placed in a lecithin-based cream at a concentration of 5% in combination with the penetration enhancer dimethylaminoethanol and applied to subjects' faces twice a day for 12 weeks.
Results: Topical alpha lipoic acid cream, at a concentration of 5%, resulted in the reduction of facial lines, and almost complete resolution of fine lines in the periorbital region and upper lip was noted in most patients. Also noted was a 50% reduction in depth of medium vertical lines on the upper lip, a significant reduction in pore size, and overall improvement in skin color and texture in all patients. There were no instances of irritation or peeling.
Conclusions: Topical 5% alpha lipoic acid cream is effective in the treatment of photo-damaged skin with no apparent adverse side effects.
Source: Nicholas V. Perricone, MD, “Topical 5% alpha lipoic acid cream in the treatment of cutaneous rhytids.” Aesthetic Surgery Journal, Volume 20, Issue 3, May 2000, Pages 218–222.
Randomized, placebo-controlled, double blind study on the clinical efficacy of a cream containing 5% alpha-lipoic acid related to photoageing of facial skin
Background: alpha-lipoic acid (LA) or the reduced form dihydrolipoate (DHLA) is a potent scavenger with anti-inflammatory properties. Previous uncontrolled studies with topical treatment with 5% LA-containing creams indicate a beneficial effect on photoageing skin.
Objective: The purpose of this study was to investigate whether a cream containing 5% LA showed any advantages concerning a number of the criteria associated with ageing of the facial skin, compared with an identical cream lacking LA.
Material and Methods: Thirty-three women, mean age 54.4 years, were included in this controlled study. After randomization half the face was treated twice daily for 12 weeks with the LA cream and the other half with the control cream. The following methods of assessment were used: self-evaluation by the test subjects, clinical evaluation, photographic evaluation and laser profilometry. Profilometry was performed before the start of treatment and at the end.
Results: All four methods of assessment showed a statistically significant improvement on the LA-treated half of the face. Laser profilometry, the most objective method used, showed an average decrease in skin roughness of 50.8% (44.9-54.0) on the LA-treated side, compared with 40.7% (32.4-48.7) on the placebo-treated half of the face P < 0.001 (Wilcoxon matched pairs test).
Conclusions: It is indicated that 12 weeks of treatment with a cream containing 5% LA improves clinical characteristics related to photoageing of facial skin.
Source: Beitner H. “Randomized, placebo-controlled, double blind study on the clinical efficacy of a cream containing 5% alpha-lipoic acid related to photoageing of facial skin.” Br J Dermatol. (2003);149 (4):841-9.
α-Lipoic acid induces collagen biosynthesis involving prolyl hydroxylase expression via activation of TGF-β-Smad signaling in human dermal fibroblasts
The collapse of collagenous networks with aging results in comprehensive changes in the functional properties of skin. α-Lipoic acid (LA) is known to possess beneficial effects against skin aging, effects often presumed to be its antioxidant potential. However, the effects of LA on fibrillogenesis in dermal fibroblasts have not been adequately assessed. In this study, we demonstrated for the first time that LA enhances the biosynthesis of new collagen in normal human dermal fibroblasts (NHDFs). By using a quantitative dye-binding method and immunochemical approaches, we showed that LA effectively increased the expression and subsequently the deposition of type I collagen in NHDFs. LA also facilitated the expression of a collagen-processing enzyme, prolyl-4-hydroxylase, pointing to the existence of a posttranslational mechanism among the LA-mediated effects on collagen synthesis. In addition, we determined that both Smad 2/3 were rapidly phosphorylated by treatment with LA within 30 min, indicating that LA enhances type I collagen synthesis through the activation of Smad signaling. Pretreatment of SB431542, a specific transforming growth factor-β (TGF-β) receptor type I (TβRI) kinase inhibitor, blocked LA-mediated Smad 2/3 phosphorylations and both type I collagen and prolyl-4-hydroxylase expression, suggesting that LA-mediated cell responses are regulated by TβRI kinase-dependent pathway. Levels of TGF-β secretion after 4 hr of treatment with LA were not remarkably elevated, indicating that LA may be able to mimic TGF-β-mediated cell response. The study results produced new insights into the molecular pharmacology of LA in NHDFs, with potential applications in the treatment of aging skin.
Source: Tsuji-Naito K, Ishikura S, Akagawa M, Saeki H. “α-Lipoic acid induces collagen biosynthesis involving prolyl hydroxylase expression via activation of TGF-β-Smad signaling in human dermal fibroblasts.” Connect Tissue Res. (2010);51(5):378-87.
Oral hyaluronan relieves wrinkles: a double-blinded, placebo-controlled study over a 12-week period
Background: Hyaluronan (HA) has critical moisturizing property and high water retention capacity especially for human skin. This study aimed to evaluate the effect of oral intake of HA.
Methods: The mean molecular weight (MW) of HA is 2 k and 300 k. Sixty Japanese male and female subjects aged 22–59 years who presented with crow’s feet wrinkles were randomly assigned to the HA 2 k or HA 300 k at 120 mg/day or the placebo group. The subjects were administered HA at a rate of 120 mg/day or a placebo for 12 weeks. The skin wrinkles were evaluated by image analysis of skin wrinkle replicas, and their skin condition was evaluated using a questionnaire survey.
Results: During the study period, the HA groups showed better level of the whole sulcus volume ratio, wrinkle area ratio, and wrinkle volume ratio than the placebo group. After 8 weeks of ingestion, the HA 300 k group showed significantly diminished wrinkles compared with the placebo group. Skin luster and suppleness significantly improved after 12 weeks in all groups compared with the baseline.
Conclusion: The results suggest that oral HA (both HA 2 k and HA 300 k) inhibits skin wrinkles and improves skin condition.
Source: Oe, M., Sakai, S., Yoshida, H., Okado, N., Kaneda, H., Masuda, Y., & Urushibata, O. “Oral hyaluronan relieves wrinkles: a double-blinded, placebo-controlled study over a 12-week period.” Clinical, cosmetic and investigational dermatology (2017), 10, 267–273.
Efficacy of a New Topical Nano-hyaluronic Acid in Humans
Background: The aim of this study was to evaluate the efficacy of a new topical low molecular nano-hyaluronic acid preparation in treating wrinkles, skin hydration, and skin elasticity in humans.
Methods: Thirty-three women with an average age of 45.2 were studied for a period of eight weeks to measure the anti-wrinkle efficacy of a new nano-hyaluronic acid. The measurements were performed in the periorbital regions by investigating the three-dimensional structure using a DermaTOP for wrinkles, Corneometer for skin hydration, Cutometer for skin elasticity, and a Chroma Meter for erythema. Thereafter, standardized images were taken and evaluated by six selected and trained raters at the end of the study for reduction of visible wrinkles as well as skin color uniformity and pigmentation.
Results: The results of 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.
Conclusion: The new nano-hyaluronic acid clearly demonstrated a significant benefit in decreasing the depth of wrinkles (up to 40%), and skin hydration (up to 96%) and skin firmness and elasticity were significantly enhanced (up to 55%) at the end of eight weeks.
Source: Jegasothy, S. M., Zabolotniaia, V., & Bielfeldt, S. “Efficacy of a New Topical Nano-hyaluronic Acid in Humans.” The Journal of clinical and aesthetic dermatology (2014), 7(3), 27–29.
A Collagen Supplement Improves Skin Hydration, Elasticity, Roughness, and Density: Results of a Randomized, Placebo-Controlled, Blind Study
The purpose of this randomized, placebo-controlled, blind study was to investigate the effects of the drinkable nutraceutical ELASTEN® (QUIRIS Healthcare, Gütersloh, Germany) on skin aging and skin health. Drinking ampoules provides a blend of 2.5 g of collagen peptides, acerola fruit extract, vitamin C, zinc, biotin, and a native vitamin E complex. This controlled interventional trial was performed on 72 healthy women aged 35 years or older. They received either the food supplement (n = 36) or a placebo (n = 36) for twelve weeks. A skin assessment was carried out and based on objective validated methods, including corneometry (skin hydration), cutometry (elasticity), the use of silicon skin replicas with optical 3D phase-shift rapid in-vivo measurements (PRIMOS) (roughness), and skin sonography (density). The verum group was followed for an additional four weeks (without intake of the test product) to evaluate the sustainability of the changes induced by the intake of the test product. The test product significantly improved skin hydration, elasticity, roughness, and density. The differences between the verum group and the placebo group were statistically significant for all test parameters. These positive effects were substantially retained during the follow-up. The measured effects were fully consistent with the subjective assessments of the study participants. The nutraceutical was well tolerated.
Source: Bolke, L., Schlippe, G., Gerß, J., & Voss, W. “A Collagen Supplement Improves Skin Hydration, Elasticity, Roughness, and Density: Results of a Randomized, Placebo-Controlled, Blind Study.” Nutrients (2019), 11(10), 2494.
Oral intake of specific bioactive collagen peptides reduces skin wrinkles and increases dermal matrix synthesis
Dietary consumption of food supplements has been found to modulate skin functions and can therefore be useful in the treatment of skin aging. However, there is only a limited number of clinical studies supporting these claims. In this double-blind, placebo-controlled study, the effectiveness of the specific bioactive collagen peptide (BCP) VERISOL® on eye wrinkle formation and stimulation of procollagen I, elastin and fibrillin biosynthesis in the skin was assessed. A hundred and fourteen women aged 45-65 years were randomized to receive 2.5 g of BCP or placebo, once daily for 8 weeks, with 57 subjects being allocated to each treatment group. Skin wrinkles were objectively measured in all subjects, before starting the treatment, after 4 and 8 weeks as well as 4 weeks after the last intake (4-week regression phase). A subgroup was established for suction blister biopsies analyzing procollagen I, elastin and fibrillin at the beginning of the treatment and after 8 weeks of intake. The ingestion of the specific BCP used in this study promoted a statistically significant reduction of eye wrinkle volume (p < 0.05) in comparison to the placebo group after 4 and 8 weeks (20%) of intake. Moreover a positive long-lasting effect was observed 4 weeks after the last BCP administration (p < 0.05). Additionally, after 8 weeks of intake a statistically significantly higher content of procollagen type I (65%) and elastin (18%) in the BCP-treated volunteers compared to the placebo-treated patients was detected. For fibrillin, a 6% increase could be determined after BCP treatment compared to the placebo, but this effect failed to reach the level of statistical significance. In conclusion, our findings demonstrate that the oral intake of specific bioactive collagen peptides (Verisol®) reduced skin wrinkles and had positive effects on dermal matrix synthesis.
Source: Proksch E, Schunck M, Zague V, Segger D, Degwert J, Oesser S. “Oral intake of specific bioactive collagen peptides reduces skin wrinkles and increases dermal matrix synthesis.” Skin Pharmacol Physiol. (2014);27(3):113-9.
Daily consumption of the collagen supplement Pure Gold Collagen® reduces visible signs of aging
With age, changes in the metabolic processes of structural components of the skin lead to visible signs of aging, such as increased dryness and wrinkle formation. The nutritional supplement, Pure Gold Collagen®, which consists of hydrolyzed collagen, hyaluronic acid, vitamins, and minerals, was developed to counteract these signs. An open-label study was conducted to investigate the effects of this nutritional supplement on skin properties. Supplementation with 50 mL of Pure Gold Collagen on a daily basis for 60 days led to a noticeable reduction in skin dryness, wrinkles, and nasolabial fold depth. In addition, a significant increase in collagen density and skin firmness was observed after 12 weeks. The data from this study suggest that Pure Gold Collagen can counteract signs of natural aging.
Source: Borumand, M., & Sibilla, S. “Daily consumption of the collagen supplement Pure Gold Collagen® reduces visible signs of aging.” Clinical interventions in aging (2014), 9, 1747–1758.
Ganoderma lucidum total triterpenes prevent radiation-induced DNA damage and apoptosis in splenic lymphocytes in vitro
The development of radioprotective agents has been the subject of intense research, especially in the field of radiotherapy. In this study, we examined the radioprotective activity of the total triterpenes isolated from Ganoderma lucidum (Fr.) P. Karst in mouse splenic lymphocytes in vitro. Using the MTT assay, Ganoderma triterpenes were found to have no effect on cell viability, indicating that they are non-toxic to splenic lymphocytes. The effect of the total triterpenes on DNA damage and apoptosis induced by radiation was analyzed using the comet assay, DNA ladder assay and flow cytometric analysis. Total triterpenes were found to be highly effective in preventing DNA laddering, even at low concentrations (25μg/ml). The comet assay demonstrated that the G. triterpenes effectively prevented DNA damage, and flow cytometry revealed a reduction in apoptotic cells. The effect of the total triterpenes on intracellular reactive oxygen species (ROS) level and endogenous antioxidant enzyme activity in splenic lymphocytes were determined to elucidate possible radioprotective mechanisms. Total triterpenes successfully reduced the formation of intracellular ROS and enhanced endogenous antioxidant enzyme activity in splenic lymphocytes following irradiation. Thus, these findings indicate that the total triterpenes isolated from G. lucidum have a remarkable ability to protect normal cells from radiation-induced damage, which suggests therapeutic potential.
Source: Smina TP, De S, Devasagayam TP, Adhikari S, Janardhanan KK. “Ganoderma lucidum total triterpenes prevent radiation-induced DNA damage and apoptosis in splenic lymphocytes in vitro.” Mutat Res. (2011);726(2):188-94.
Emerging Roles of Ganoderma Lucidum in Anti-Aging
Ganoderma lucidum is a white-rot fungus that has been viewed as a traditional Chinese tonic for promoting health and longevity. It has been revealed that several extractions from Ganoderma lucidum, such as Ethanol extract, aqueous extract, mycelia extract, water soluble extract of the culture medium of Ganoderma lucidum mycelia, Ganodermasides A, B, C, D, and some bioactive components of Ganoderma lucidum, including Reishi Polysaccharide Fraction 3, Ganoderma lucidum polysaccharides I, II, III, IV, Ganoderma lucidum peptide, Ganoderma polysaccharide peptide, total G. lucidum triterpenes and Ganoderic acid C1 could exert lifespan elongation or related activities. Although the use of Ganoderma lucidum as an elixir has been around for thousands of years, studies revealing its effect of lifespan extension are only the tip of the iceberg. Besides which, the kinds of extractions or components being comfrimed to be anti-aging are too few compared with the large amounts of Ganoderma lucidum extractions or constituients being discovered. This review aims to lay the ground for fully elucidating the potential mechanisms of Ganoderma lucidum underlying anti-aging effect and its clinical application.
Source: Wang, J., Cao, B., Zhao, H., & Feng, J. “Emerging Roles of Ganoderma Lucidum in Anti-Aging.” Aging and disease (2017), 8(6), 691–707.
Using Copper to Improve the Well-Being of the Skin
Copper has two key properties that are being exploited in consumer and medical device products in the last decade. On the one hand, copper has potent biocidal properties. On the other hand, copper is involved in numerous physiological and metabolic processes critical for the appropriate functioning of almost all tissues in the human body. In the skin, copper is involved in the synthesis and stabilization of extracellular matrix skin proteins and angiogenesis. This manuscript reviews clinical studies that show that the use of textile consumer and medical device products, embedded with microscopic copper oxide particles, improve the well-being of the skin. These include studies showing a) cure of athlete’s foot infections and improvement in skin elasticity, especially important for individuals suffering from diabetes; b) reduction of facial fine line and wrinkles; and c) enhancement of wound healing; by copper oxide embedded socks, pillowcases and wound dressings, respectively. The manuscript also reviews and discusses the mechanisms by which the presence of copper in these products improves skin well-being.
Source: Borkow G. “Using Copper to Improve the Well-Being of the Skin.” Current chemical biology (2014), 8(2), 89–102.
Selenium: its role as antioxidant in human health
Selenium (Se) is an essential trace element, and its low status in humans has been linked to increased risk of various diseases, such as cancer and heart disease. In recent years, Se research has attracted tremendous interest because of its important role in antioxidant selenoproteins for protection against oxidative stress initiated by excess reactive oxygen species (ROS) and reactive nitrogen species (NOS). The synthesis of selenoproteins requires a unique incorporation of amino acid selenocysteine (Sec) into proteins directed by the UGA codon, which is also a termination codon. Interest in Se research has led to the discovery of at least 30 selenoproteins; however, the biochemical functional roles of some of these selenoproteins are still unknown. Besides in the form of selenoproteins, Se can exist in many different chemical forms in biological materials either as organic Se compounds, such as selenomethionine and dimethylselenide, and inorganic selenites and selenates. In foods, Se is predominantly present as selenomethionine, which is an important source of dietary Se in humans, and also as a chemical form that is commonly used for Se supplements in clinical trials. Concern for potential deficiency diseases associated with low Se status has led to the establishment of the recommended daily requirements for Se in many countries. However, excess Se intakes through supplementation and its potential misuse as health therapy could also pose a risk of adverse health effects if its use is not properly regulated.
Source: Tinggi U. “Selenium: its role as antioxidant in human health.” Environmental health and preventive medicine (2008), 13(2), 102–108.
Effects of plant sterols derived from Aloe vera gel on human dermal fibroblasts in vitro and on skin condition in Japanese women
Background: Aloe is known for its topical use for treating wounds and burns. Many previous studies reported the healing effects of Aloe vera. However, there are few clinical studies on the effect of orally administered A. vera gel on the skin. Aloe sterols are a type of plant sterols that have the capability to regulate the metabolism of glucose and lipids. In a recent study, we confirmed that ingested Aloe sterols reached the peripheral tissues through the bloodstream. However, their influence on dermal fibroblasts has not been investigated.
Methods: First, we investigated the capability of Aloe sterols (cycloartenol and lophenol) to stimulate human dermal fibroblasts in vitro. Then, we investigated the effect of intake of Aloe vera gel powder (AVGP) containing 40 μg Aloe sterols on the skin conditions in Japanese women with dry skin in a randomized, double-blind, placebo-controlled trial.
Results: After cocultivation with Aloe sterols, the production of collagen and hyaluronic acid increased by approximately two-fold and 1.5-fold, and gene expression levels of these enzymes responsible for their synthesis were also observed in human dermal fibroblasts. An increase in arm skin hydration was observed at 8 weeks in the AVGP group, whereas a slight decrease in arm skin hydration was noted in the placebo group. However, there was no statistical difference between AVGP and placebo groups in skin moisture. In subgroup analysis, the change in the mean wrinkle depth was significantly lower in the AVGP group than in the control group. In addition, percent body fat after 8 weeks was significantly lower in the AVGP group. No AVGP intake-dependent harmful phenomenon was observed during the intake period.
Conclusion: The present study confirms that daily oral Aloe sterol-containing AVGP significantly reduced facial wrinkles in women aged ≥40 years, and Aloe sterols stimulate collagen and hyaluronic acid production by human dermal fibroblasts.
Source: Tanaka, M., Misawa, E., Yamauchi, K., Abe, F., & Ishizaki, C. “Effects of plant sterols derived from Aloe vera gel on human dermal fibroblasts in vitro and on skin condition in Japanese women.” Clinical, cosmetic and investigational dermatology (2015), 8, 95–104.
Methylsulfonylmethane: Applications and Safety of a Novel Dietary Supplement
Methylsulfonylmethane (MSM) has become a popular dietary supplement used for a variety of purposes, including its most common use as an anti-inflammatory agent. It has been well-investigated in animal models, as well as in human clinical trials and experiments. A variety of health-specific outcome measures are improved with MSM supplementation, including inflammation, joint/muscle pain, oxidative stress, and antioxidant capacity. Initial evidence is available regarding the dose of MSM needed to provide benefit, although additional work is underway to determine the precise dose and time course of treatment needed to provide optimal benefits. As a Generally Recognized As Safe (GRAS) approved substance, MSM is well-tolerated by most individuals at dosages of up to four grams daily, with few known and mild side effects. This review provides an overview of MSM, with details regarding its common uses and applications as a dietary supplement, as well as its safety for consumption.
- Butawan, M., Benjamin, R. L., & Bloomer, R. J. “Methylsulfonylmethane: Applications and Safety of a Novel Dietary Supplement.” Nutrients (2017), 9(3), 290.
- Bhupendra Singh, Trenton R. Schoeb, Prachi Bajpai, Andrzej Slominski, Keshav K. Singh. Reversing wrinkled skin and hair loss in mice by restoring mitochondrial function. Cell Death & Disease, 2018; 9 (7)
- Beitner H. Randomized, placebo-controlled, double blind study on the clinical efficacy of a cream containing 5% alpha-lipoic acid related to photoageing of facial skin. Br J Dermatol. Oct 2003;149 (4):841-9.
- Jegasothy SM, Zabolotniaia V, Bielfeldt S. Efficacy of a New Topical Nano-hyaluronic Acid in Humans. J Clin Aesthet Dermatol. 2014;7(3):27-29.