Injuv: A Better Hyaluronic Acid by Rachel Adams
Injuv:
A Better Hyaluronic Acid C
onsumers are looking for safe “beauty from within” products that can help smooth skin and aid in wound healing. According to a 2011 report from Global Industry Analysts, the global nutricosmetics market is forecasted to reach USD $4.24 billion by 2017. In the United States, nutricosmetics are projected to experience a CAGR (compound annual growth rate) of 14 percent through 2017, the report noted. “Natural” is an important component of the growth of beauty products. Sales within the global natural personal care market increased by almost 10 percent in 2014, according to research firm
Kline & Co. Further, consumers in the United States and Europe are increasingly purchasing beauty products containing natural ingredients, and the natural beauty market is expected to reach a CAGR of 10 percent through 2019, Kline reported. In addition, a beauty online survey conducted by Nielsen showed 53 percent of consumers said “all natural” on beauty product labels is “very” or “moderately” important. Other claims consumers find “very” or “moderately” important on their beauty products include “anti-wrinkle/anti-aging” (44 percent) and “skin lifting/firming and firming” (44 percent). However, natural is just one aspect consumers value; efficacy and safety are also important, and need to be reinforced by adequate research.
Hyaluronic Acid for Skin Health
Hyaluronic acid (HA) is a proven ingredient that benefits skin health, but many offerings on the market may not be bioavailable. HA is found in several parts of the body and is responsible for several important functions. In addition to the skin, Jeanette Fisher, RDN, marketing director, Soft Gel Technologies Inc., said HA is found in the synovial fluid (contained in the membrane that surrounds the joints), the vitreous
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by Rachel Adams
humor of the eye, cartilage, blood vessels, extracellular matrix (ECM) and the umbilical cord. According to Fisher, one of the most important biological functions of HA is its ability to retain water. This is true for HA’s benefit to skin health, which is conveyed via its role in the ECM. Fisher explained that the ECM is produced by the cells and excreted to the extracellular space within the tissues throughout the body, including the skin. Specifically, HA lends structure to the matrix, but also allows it to “lock in moisture” by holding onto water molecules in the matrix. When the ECM fills the extracellular space in the skin, the skin is soft, smooth, moist and elastic. “The ECM has great influence on the integrity and appearance of the skin,” Fisher said. “Cells are surrounded by the ECM—a flexible network containing several classes of proteins, glycoproteins (collagen), proteoglycans and HA.” A 1994 study published in the Journal of Investigative Dermatology found that HA acts as a sponge to hold onto water within the cells throughout the body.1 Importantly, the study also found that aging causes a decrease in the synthesis and a recompartmentalization of HA. Recompartmentalization of HA refers to the transfer of HA from the epidermis to the dermis, explained Fisher. “The decrease in synthesis of HA and the recompartmentalization
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both leave the epidermis depleted in HA, resulting in ‘aged’ skin,” she said. HA’s ability to retain water and promote hydration may be a mechanism for maintaining the normal hydration of skin. “As such, decreasing levels of HA deposition might underlie the changes associated with the aging process,” Fisher said. HA’s additional benefits to the skin include its role in the proper transfer of nutrition and the removal of metabolic waste, 2 and its role in the proper healing of scars.3 HA supplementation can be especially beneficial for the skin; according to Fisher, the half-life of HA in the cartilage is two to three weeks, but the half-life of HA in the epidermis is less than one day. Therefore, daily supplementation allows HA levels to stay consistent.
Injuv Provides Better Bioavailability
Despite its researched benefits, supplementation with standard HA is not always effective due to the size of the HA molecule. “The natural weight of hyaluronic acid is 1.2 million to 1.5 million daltons,” Fisher said, adding that daltons are an arbitrary unit of mass. “This is a molecule that is far too large to pass through the digestive tract and enter the bloodstream.”
However, a technique developed by scientists in Japan—an enzymecleaving technique—allows for absorption of the molecule, said Steve Holtby, president and CEO of Soft Gel. “By using an enzymecleaving technique, naturallyderived hyaluronic acid [from rooster combs] is broken down into lower molecular weight polymers.” Lower molecular weight polymers are formed by the joining of smaller molecules, Fisher added. The cleaving process is patented in Japan (Japanese Patent no. 2971860). Injuv® by Soft Gel Technologies is a low-molecular weight HA complex standardized to 9-percent HA. Each softgel contains 70 mg of Injuv and provides 6.3 mg of HA derived from rooster comb. According to Fisher, “Rooster combs are a very rich source of HA and the purest natural source of HA available.”
Componential analysis on Injuv Analysis item
%
Volume of water
2.2~2.6 *1
3.84
Total protein amount
3.04
Content of Nitrogen
*2
Free amino acid
4.08
*3
N-acetylglucosamine
*4
0 13.4
HA content*5
*1. Semi-micro Kieldahl method *2. Lowry method *3. Ninhydrin process *4. MorganElson method *5. HPLC method
In addition, the HA in Injuv has been enzymatically cleaved. No heat is required for the enzyme-cleaving process; very high heat can denature enzymes. According to Holtby, “When the enzymes are applied, the HA gets cleaved into shorter chains—from
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disaccharides to oligosaccharides. The low-molecular weight polymers measure around 5,000 daltons, on average”—a size much smaller than that of a standard HA molecule, making it possible to for the HA in Injuv to be absorbed by the body. The end-result is an internal cosmeceutical that hydrates skin via a softgel delivery system “with proven absorption and bioavailability,” Holtby said. Past supplementation with HA has been in the form of injection or topical application, Fisher said, “but was a large polymeric structure. Injuv is a low-molecular weight hyaluronic acid supplement providing internal moisture for healthier skin and joints.”
Injuv’s Proven Effects
Multiple clinical trials have been conducted to determine the absorption and bioavailability of Injuv, as well as its benefits to skin health. “Science looks for a clinical endpoint when conducting research,” Fisher said. “In the case of Injuv, wound healing as an endpoint is a way to indicate absorption.” In order for absorption to occur, Injuv must be able to enter the epithelial cells of the small intestine, Fisher said. In addition, it must be able to go from the dermis to the epidermis, and from the synovial fluid to the cartilage. In an unpublished mouse study, Injuv significantly improved normal wound healing compared to placebo. For the study, a skin wound was induced on 30 mice while under anesthesia. The mice were divided into three groups and administered either Injuv (containing 9 percent HA) orally; a known wound-healing enhancer (CGS-21680, by Novartis), which was applied topically; or sterile
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Wound Half-Closure Time— CT50 Linear Regression Analysis 10 9
Days
8
Placebo
9
7
Injuv ®
6
6.5
5 4 3 2 1
CGS-21680
5.3
100
Percent Wound Half-Closure Time
90 80
Closure of Wound (%)
saline orally. The wound area was measured each day and quantified using an image analyzer (Life Science Resources VISTA v.30). The wound half-closure time (CT50) was determined by linear regression analysis using GraphPad Prism software. The results determined that Injuv significantly improved normal wound healing on a daily basis when administered orally compared to placebo. Further, there was little difference between the activity of oral Injuv and the topical woundhealing enhancer. In addition, the study results indicated that the half-closure time was dramatically reduced versus placebo.
70
* p <0.01
n=30
Placebo
Injuv
CGS-21680
®
63.5
56.6 51.7
50
50
44.5
42.3
40
37.1
32.8 33.4
30 20
79.6
68.3 61.1
60
76.4
28.1 19.4
10 0
3
5
7
9
11
Time Event (Days)
Injuv was also tested in humans to determine its effects on skin health. In an unpublished preclinical trial at Otsuma Women’s University in Japan evaluating 96 women aged 22 to 65 years, Injuv showed dramatic improvements of several physiological parameters, including face moisture, skin smoothness and firmness, as well as improvements to joint mobility and pain associated with age or arthritis. In the study, participants received Injuv via six 70-mg tablets standardized to 9 percent HA, which provided 37.8 mg/d of HA
for 45 days. Subjective monitoring was conducted via a questionnaire that assessed skin moisture, smoothness and firmness, in which: 84 percent reported a great improvement in the moisture levels of their hands and face; 83 percent reported a great improvement in the smoothness of their skin; 78 percent reported a great improvement in the softness of their elbows, knees and hands; and 50 percent reported a great improvement in the stiffness of their joints.
number of subjects
Skin Effects 80 60
81
80
40 20 0
12 4
8 8 face moisture
skin smoothness
■ Greatly Improved
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75
■ Improved
12 9 elbows, knees, heels
■ No Improvement
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A human study presented in 2009 at the Nutracon and SupplyExpo conference in Anaheim, California, measured the effects of Injuv on skin moisture content, and found supplementation with Injuv (two 70-mg softgels twice daily) for 30 days improved skin moisture content compared to baseline measurements, as well as when compared to placebo.4 The study evaluated 107 participants aged 30 to 50 years with a skin moisture content value of 12 or less. Participants were healthy individuals and maintained their normal dietary and lifestyle habits throughout the study. Skin surface moisture content was measured before and after supplementation using an SHP88 probe. “Supplementation with Injuv moisturizes skin from the inside out, thereby decreasing the appearance
Comparison of Skin Moisture Content and pH Value Between Injuv-treated and Control Groups Moisture
content
pH
value
Baseline
Postadministration
Baseline
Postadministration
Groups
n
Injuv-treated
52 46.60±9.75
67.53±18.60**##
5.20±0.64
5.53±0.64**##
Control
55 45.60±7.90
55.04±18.33
5.10±0.63
5.24±0.61**
**: p<0.01 for intra-group comparison (vs. baseline) ##: p<0.01 for inter-group comparison (vs. control)
of fine lines and aging,” Holtby said. In addition, he noted Injuv can increase HA content throughout the body and can help the skin stay healthy by removing toxins and metabolic waste products, as well as helping the skin stay nourished. As consumers continue to seek products that will promote outer
beauty via a healthy interior, proven efficacy of beauty from within products will be key. In the case of HA, bioavailability and absorption are challenges that can affect a product’s performance, and Injuv has research that supports its ability to overcome both. ◆
References 1. Meyer LJM et al. “Age-dependent changes of hyaluronan in human skin.” Journal of Investigative Dermatology. 1994;102:385-389. 2. Sakai S et al. “Hyaluronan exists in the normal stratum corneum.” Journal of Investigative Dermatology. 2000;114:1184-1187. 3. Meyer LJM et al. “Reduced hyaluronan in keloid tissue and cultured keloid fibroblasts.” Journal of Investigative Dermatology. 2000;114:953-959. 4. Wakayama S, presenter. “Clinical study on Injuv® demonstrates improvement of skin moisture content.” Poster session presented at the March 2009 Nutracon and SupplyExpo conference, Anaheim, CA.
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