An Annual feature since 2002, this special section of Nutrition Industry Executive (NIE) is designed to help manufacturers gain a better understanding of the ingredients and services available that can make their products stand out. It gives the magazine’s advertisers an opportunity to describe in some detail the research that goes into their branded ingredients, products and company services.

These companies have responded to this opportunity with background information about the health concerns their products are intended to address, histories of nutrients behind their ingredients and details of research that have been carried out.We’ve also provided company addresses, phone numbers, email and website addresses to make obtaining additional information as easy as possible.

Following is an index of companies participating in this year’s NIE Science of Supplements section:

Saving Money on Safety Studies Without Compromising Quality

Over the last decade there has been a dramatic increase in the number of safety studies conducted on nutraceutical and functional ingredients. Navigating the complexities associated with selecting the right studies and laboratories is challenging enough, not to mention funding them. This is why seeking services from a company with decades of experience in commissioning and monitoring toxicological studies can reduce the burden of approving these safety studies. Making costly mistakes, such as approving a protocol that does not meet U.S. regulatory compliance or paying for unnecessary studies, can be avoided. Knowing how to determine the quality of toxicological studies in order to meet FDA regulatory compliance is cost effective and time saving.

Having a comprehensive body of evidence for a product’s safety is of the utmost importance in addition to providing the necessary support for GRAS self-affirmations and New Dietary Ingredient notifications to the FDA. Furthermore, in this litigious society, having such evidence can make the difference between winning and losing a potential lawsuit. For well-researched ingredients and products, there may be a body of literature available in the public domain to support safety. These may be found in peer-reviewed academic journals indexed by the National Library of Medicine at its PubMed website. When studies are lacking, the best approach is to conduct a comprehensive safety assessment that investigates genotoxicity, potential drug interactions, as well as in vivo acute and sub-acute oral toxicity (i.e., 90-day repeated oral toxicity with histopathologies), or other relevant safety assessments.

These studies take time and require a financial investment, so choosing the right laboratory to conduct studies is important. Labs in the U.S. and Western Europe may tend to be more expensive than those located in developing countries. Thus, there is an inclination to consider such labs when “shopping” for safety studies to lower costs. However, many labs lack the decades of historical data on studies available in established labs, which can become vitally important when it comes time to interpret study results or prepare manuscripts for publication in ranked, peer-reviewed toxicology journals.

Because there could potentially be a perception problem with regard to the quality of studies performed outside of North America and Europe, it is essential to understand the criteria for evaluating potential toxicology laboratories. Firstly, make sure the lab meets good laboratory practice (GLP) requirements, and is certified by an internationally recognized health-monitoring agency. Secondly, make sure the study director is a qualified PhD toxicologist. Thirdly, and very importantly, make sure the studies are designed to comply with well-accepted toxicological protocols such as found in the FDA Redbook: Toxicological Principles for the Safety Assessment of Food Ingredients, or OECD Guidelines for the Testing of Chemicals and its revisions. Often, studies cost less because some aspect of the protocol has been modified to reduce cost.

Many companies have come to AIBMR Life Sciences for assistance with Self-affirmed GRAS determinations and eventual FDA GRAS notifications. There have been several occasions where toxicological studies performed or were quoted before contacting AIBMR did not meet the aforementioned protocols, and were therefore not predictive of safety based upon reliably established scientific principles and procedures. For example, in a 90-day repeated, oral-toxicity study, five animals or fewer per sex per group may have been used (likely in an attempt to save money), rather than 10-20 as recommended by the FDA Redbook or OECD protocols, or animals may have been housed in large groups, which can confound results.

Clearly, since a 90-day study takes roughly five months to complete and report, conducting studies that don’t meet FDA recommendations is a waste of both time and money, and could even cost a manufacturer more by losing a first-to-market opportunity. Having to repeat such a study properly would set a company back an additional six months, not to mention tens if not hundreds of thousands of dollars. In conclusion, no matter what laboratory is in consideration for placing toxicological studies, it is prudent to have experts in the field review the protocols to be sure they are compliant from a regulatory perspective.

Alexander G. Schauss, PhD, FACN, is senior director of research at AIBMR Life Sciences and a member of the American College of Toxicology and the Society of Toxicology; John R. Endres, ND, is the company’s CSO and Amy Clewell, ND, is senior research associate. AIBMR guides global ingredient firms and product manufacturers through the process of GRAS self-affirmation and FDA notification, while providing a complete range of natural product consulting and regulatory compliance services.

PhosphoLean NOPE+EGCG For Safe and Successful Weight Management

The pain of dieting: binge eating, high stress and depression, which bring failure. Clearly, it has been shown that one-third of people drop off their diets in the crucial first few weeks, and as a result, they experience little if any success. And in many cases, they actually end up in worse shape from both psychological and metabolic standpoints. In the final analysis, the simple key to success for any individual on any calorie-reduced diet is “length on the diet.” The simple truth is weightloss efforts are painful and true success takes time.

As a result, in nearly every diet study involving pharmaceuticals, nutraceuticals and exercise programs, one-third of the dieters drop off the diet in the crucial first to third weeks. The results are nearly always identical as misery and failure are experienced, and in the end, little if any measurable weight loss is achieved. Worse yet, dieters do not experience even the bare minimum days of diet duration required to restructure their eating and exercise behaviors. Further, depression and weight regain very commonly experienced.

A True Scientific Approach for Overweight and Obesity Control

Recent research involving the manipulation of appetite has shown that suppressing appetite and thus reducing the intake of food can be a very effective means of controlling energy balance. And science has proven that the type of diet really does not matter. Total calories matters—plain and simple. But the real fact is that weight management is so complex that scientists struggle to fully understand the physiological mechanisms that actually control weight.

Since appetite suppression is a major controlling point for energy (food) intake, managing appetite is one of the most important approaches to controlling healthy body weight, especially when combined with health conscious lifestyle choices that include attention to proper food intake and exercise.

PhosphoLean NOPE + EGCG to the Rescue 

PhosphoLean® is a patented, natural compound of N-oleoylphosphatidyl- ethanolamine (NOPE) and EGCG, and it has been clinically proven to help dieters stay on their diets.

No matter what reduced-calorie diet a person is on, these symptoms are typically experienced:

• Hunger pangs

• Diet stress

• Binge eating

• Depression and moodiness In a recent study, PhosphoLean significantly improved diet compliance in a group of healthy, overweight or obese subjects, as demonstrated by dropout rate. It also increased satiety, decreased depressive symptoms, decreased bingeeating severity and provided favorable changes in insulin resistance and lipids.

Recent research has shown that oleoyl ethanolamine (OEA), the active compound liberated from PhosphoLean binds to a cell receptor class called peroxisomeproliferator- activated receptor-alpha (PPAR-á) found in the intestinal tract.

The Science of How PhosphoLean Works 

After oral administration, PhosphoLean is gastro-protected in the stomach, and in the intestinal tract, OEA—a newly discovered lipid mediator involved in the regulation of feeding—is enzymatically liberated. Recent research has shown that OEA binds to a cell receptor class called PPAR-á found in the intestinal tract. These receptors, when activated, are responsible for signaling the brain center to decrease appetite and, hence, to reduce food intake and body weight gain. This signal is “hard-wired” to the brain, where appetite suppression is switched on. The EGCG polyphenols in PhosphoLean act synergistically with OEA via sympathetic activation of thermogenesis and increased fat oxidation, thus enhancing the compound’s weight management effects. The result is that inspired dieters can stick to their longterm diets and achieve success!

Efficacy and Proven Safety of PhosphoLean

In terms of safety, a number of acute toxicity studies have proven that PhosphoLean is unquestionably well tolerated and safe, and additional research and safety studies have proven that important biomarkers including plasma cholesterol and triglyceride levels, lipoperoxide levels and mitochondrial stress, are all positively impacted as well.

DPA: An Increasingly Crucial Link for Heart Health and Cognitive Function

Building the Case for DPA 

For more than 30 years, extensive scientific and clinical research has been conducted on the potential therapeutic and nutritional value of long-chain omega-3 fatty acids in human health and nutrition.
Long-chain omega-3 fatty acids are required for human health, but are not produced by the body. The collective research on omega-3 fish oils has demonstrated therapeutic benefits in regards to neural function, inflammation, cardiovascular disease, and cholesterol and lipid profiles.

In recent years, research has been tailored to reflect specific individual fatty acids, of which the most popular include EPA and DHA. These two fatty acids are commonly found in numerous fish species. However, there is another fatty acid, an intermediary between EPA and DHA called docosapentaenoic acid (DPA), which has recently been called the “missing link” to the larger health puzzle.

DPA has increasingly caught the attention of the medical and scientific communities, as developing research is showing its distinct and powerful role as a nutritional and therapeutic supplement in such diverse conditions as cardiovascular disease, cognitive decline, and cholesterol and triglyceride health.

DPA: A Current Scientific Overview

While a variety of fish oils are good sources of omega-3 fatty acids, the majority of these lack a meaningful amount of DPA. Emerging evidence now seems to indicate DPA plays a substantial role in nutritional supplementation, as it has therapeutic potential to work synergistically with EPA and DHA, and as a stand-alone fatty acid. Below is a summary of the most significant, current scientific findings: 

• While much work has previously shown that omega-3 fatty acids can play a protective role in preventing cardiovascular disease, two clinical studies have demonstrated a positive correlation between DPA and the prevention of cardiovascular disease in humans.

First, researchers in Eastern Finland published a study demonstrating DPA’s role in reducing the risk of acute coronary events. Second, a Japanese study published five years later further corroborated these findings and additionally found a significant association between DPA supplementation and reduced cardiovascular disease.

In addition, DPA has been reported to have a positive role in reducing the expression of inflammatory genes, thereby improving cardiovascular health.

• Over the years, numerous studies have demonstrated that EPA and DHA can lower triglycerides (TG) and cholesterol levels in the plasma and liver. Recently, similar research has shown that DPA also possess lipid metabolism improving effects similar to EPA and DHA. Results point to a synergistic potential of the three compounds in nutritional supplementation for improving cholesterol and TG levels.

• Within the last year, researchers at Trinity College in Dublin, Ireland, published a groundbreaking study that demonstrated DPA plays a significant role in protecting against normal cognitive decline due to aging and general loss of synaptic function. By supplementing the normal diets of rats with DPA, it was found that DPA possesses neuro-restorative effects in the hippocampus of these rats by decreasing two major biochemical mechanisms: microglial activation and oxidative stress. 

Menhaden: A Significant Source of DPA Fish oil sourced from the menhaden species—marketed as OmegaPure® for functional foods and OmegaActiv™ for dietary supplements—is regarded as the No.1 source of DPA, based on USDA (US Department of Agriculture) National Nutrient Database Release 22 (SR22).

DPA is important to overall bodily function, as nearly one-third of the long-chain omega-3 fatty acids circulating in human blood are attributable to DPA.

Omega-3 fatty acids have consistently been shown to play a positive role in preventative and protective health and are now thought to be an important part of any healthy lifestyle. While more scientific and clinical work remains to be done to fully understand and comprehend the role of DPA as a nutritional supplement, it is becoming clear that fish oil supplementation containing DPA —in addition to EPA and DHA—most likely represents a more powerful synergistic nutritional supplement compared with oil extracts containing EPA and DHA alone.

For a complete list of references, visit www.niemagazine.com.

Purple Sweet Potato Extract: A Novel Colored Ingredient for Foods, Beverages and Health Product Formulations

Purple sweet potato is an intensely colorful, fiber-rich, low fat, low sugar, naturally sweet powerhouse of vitamins, minerals, soluble fiber and deep pigmented red, blue and purple antioxidant plant compounds. Originally from South and Central America and the West Indies, purple sweet potatoes have spread all over the world. The sweet potato has the botanical name Ipomoea batatas, which belongs to the morning glory family (Convolvulaceae). It is naturally found with many color variations based on the variation of plant pigments, carotenes and anthocyanins.

Purple sweet potato provides natural color, antioxidants and nutrients to beverages and processed foods, including puddings, ice cream/sherbet/sorbet, dessert fillings, custards, breads, and dried snack foods. In the Philippines, a medium bright lavender color from purple sweet potatoes is known as “ube,” which gives a beautiful color to foods, including pastries, ice cream and puddings. 

A concentrated, water-soluble, botanical extract from purple sweet potato provides a rich concentration purple color anthocyanin pigments for formulating into specialty products. The extract can be used in foods, beverages and in dietary supplements formulated into capsules and tablets.1 This unique food, and its anthocyanin compounds, has been studied in many health areas. Research has shown that purple sweet potato extract effectively increases plasma antioxidant capacity significantly from the absorption of phenolic compounds.2 Purple sweet potatoes are rich in antioxidant compounds and contain as much as 19.78mg/100g anthocyanins and 61.55mg/g total phenolics. 3 

The total antioxidant capacity of purple-fleshed sweet potatoes has the ORAC value comparable to apples, cherries, oranges, pears, broccoli and eggplant.4 For liver health, anthocyanins from purple sweet potato exhibit antioxidant and hepatoprotective activities. One study showed that anthocyanins could reduce liver injury by inducing antioxidant enzymes and reducing expression of COX-2 and iNOS inflammation enzymes. The anthocyanins protected against liver fibrosis, reduced oxidative stress, liver inflammation and acetaminophen- induced liver damage in animal experiments.5-7 Men were treated for borderline hepatitis with 200mg anthocyanins in 125ml of purple sweet potato concentrate during a randomized, double-blind, placebo-controlled, parallel study. Liver enzymes significantly decreased, particularly the GGT level.8 In brain health research, purple sweet potato anthocyanins had several beneficial effects. 

It reduced death of brain cells caused by beta-amyloid oxidative stress, and suppressed acute inflammation in brain tissue exposed to lipopolysaccharides. In aging animal brains, anthocyanins reduced cognitive deficit, oxidative damage and inflammation. 9 Purple sweet potato color improved spatial learning and memory deficits by regulating the expression of synaptic proteins after impairment by d-galactose.10 


The cardiovascular benefits are many. Blood pressure-lowering effects were observed in hypertensive animals fed with one percent pure anthocyanins from purple sweet potatoes.11 In a separate cardiovascular-related experiment, the development of atherosclerotic lesions was reduced and protein glycation was inhibited by the extract.12 Plasma antioxidant capacity is significantly elevated after absorption of these anthocyanins, which also helped to protect LDL cholesterol from oxidation. Anti-hyperglycemic effects were found from its diacylated anthocyanin derived from through the inhibitory action of alpha-glucosidase on the rate of starch digestion and absorption.13 

Other properties include anticancer effects in colorectal cancer studies, and improved immunity of the thymus gland protected from radiation damage. Antimutagenic effects helped counteract heterocyclic amine mutagens.

Irvingia Gabonensis: African Wild Mango

Also known as wild mango and bush mango, Irvingia gabonensis comes at a time when not only the U.S., but the world continues to fight the battle of the bulge. According to the CDC’s Behavioral Risk Factor Surveillance System (BRFSS), more than half of the population in the entire U.S. is either overweight or obese.

What is Irvingia Gabonesis?

Irvingia is a genus of African and Southeast Asian trees in the family Irvingiaceae, sometimes known by the common names wild mango, African mango or bush mango. They bear edible mango-like fruits, and are especially valued for their fat- and protein-rich nuts, known as ogbono, etima, odika or dika nuts.

The subtly aromatic nuts are typically dried in the sun for preservation and are sold whole or in powder form. They may be ground to a paste known variously as dika bread or Gabon chocolate. Their high content of mucilage enables them to be used as thickening agents for dishes such as ogbono soup. The nuts may also be pressed for vegetable oil.

Weight Management Benefits 

Irvingia gabonensis has been shown to significantly reduce body weight and improve metabolic parameters in overweight humans in a randomized, doubleblind, placebo-controlled investigation.

An extract of the African plant Irvingia gabonensis shows tremendous promise in correcting leptin resistance, promoting weight loss and combating components of metabolic syndrome.

In a double-blind study, overweight but otherwise healthy individuals who supplemented with Irvingia extract lost an average of 28 pounds over the course of 10 weeks. Body fat percentage and waist circumference decreased, as did metabolic parameters including cholesterol, LDL, C-reactive protein and fasting glucose. Irvingia facilitates the breakdown of body fat by reducing an enzyme (glycerol- 3-phosphate dehydrogenase) that enables glucose to be stored as triglyceride in fat cells. Furthermore, Irvingia increases the insulin-sensitizing hormone adiponectin and inhibits the digestive enzyme amylase, which is involved in carbohydrate digestion.
Clinical research to date suggests that Irvingia gabonensis at a dose of 150mg twice daily is a safe, effective method to lose excess body fat and fight components of the metabolic syndrome. (Source: Life Extension Magazine) 

Clinical Study

The following clinical abstract was taken from the study conducted by Laboratory of Nutrition and Nutritional Biochemistry, Faculty of Science, University of Yaounde I, Yaounde, Cameroon and Department of Food Science and Nutrition, ENSAI, University of Ngaoundere, BP 686 Ngaoundere, Cameroon.

A recent in vitro study indicates that IGOB131, a novel seed extract of the traditional West African food plant Irvingia gabonensis, favorably impacts adipogenesis through a variety of critical metabolic pathways including PPAR gamma, leptin, adiponectin and glycerol-3 phosphate dehydrogenase. This study was therefore aimed at evaluating the effects of IGOB131 on body weight and associated metabolic parameters in overweight human volunteers.

The study participants comprised of 102 healthy, overweight and/or obese volunteers (defined as BMI > 25 kg/m) randomly divided into two groups. The groups received on a daily basis, either 150mg of IGOB131 or matching placebo in a double-blinded fashion, 30-60 minutes before lunch and dinner. At baseline, four, eight and 10 weeks of the study, subjects were evaluated for changes in anthropometrics and metabolic parameters to include fasting lipids, blood glucose, Creactive protein, adiponectin and leptin.

Significant improvements in body weight, body fat and waist circumference as well as plasma total cholesterol, LDL cholesterol, blood glucose, C-reactive protein, adiponectin and leptin levels were observed in the IGOB131 group compared with the placebo group.

Irvingia gabonensis administered 150mg twice daily before meals to overweight and/or obese human volunteers favorably impacts body weight and a variety of parameters characteristic of the metabolic syndrome. This is the first double-blind, randomized, placebo-controlled clinical trial regarding the anti-obesity and lipid profile modulating effects of an Irvingia gabonensis extract. The positive clinical results, together with [researchers] previously published mechanisms of gene expression modulation related to key metabolic pathways in lipid metabolism, provide impetus for much larger clinical studies. Irvingia gabonensis extract may prove to be a useful tool in dealing with the emerging global epidemics of obesity, hyperlipidemia, insulin resistance and their co-morbid conditions.

Glutathione: A Master Antioxidant for Cellular Protection

Glutathione (GSH), a small peptide comprised of three common amino acids, is one of the primary protective molecules in the body. Its scientific name is N-(N-L-gamma- Glutamyl-L-cysteinyl)glycine.

GSH is present in all tissues and body fluids, both inside and outside of cells. The entire body pool is made and degraded daily through a continuous turnover of both cellular and extracellular glutathione. In most cases, GSH is released from cells and converted to precursor amino acids, which are absorbed and recombined to make new GSH. Cells of the intestinal tract, lung, kidney and possibly brain have specific transport systems to take up intact glutathione, but the liver and most other sites take up the individual amino acids and re-synthesize them to GSH.2,6,10
Sources

Glutathione is provided both through the diet and endogenous synthesis. The best food sources are fresh fruits and vegetables, and freshly prepared meats1. Most methods of food processing destroy glutathione; therefore, processed foods, dairy foods and grain products are poor sources. 

Glutathione is also available in dietary supplements, and Kyowa Hakko USA offers the branded ingredient Setria® glutathione. Setria is pure, stable and allergen- free, and manufactured using a GMP-compliant, proprietary fermentation process that preserves bioavailability.

Roles in Health

The central roles of glutathione in maintaining redox balance and in detoxifying compounds suggest protective roles in all conditions related to oxidative stress. Although large-scale clinical trials still need to be conducted, many observational and laboratory studies suggest:

• Glutathione decreases with aging, beginning in midlife and plunging precipitously after age 6011,12 and healthy elders have high blood glutathione concentrations.13

• Higher glutathione status in older individuals has been correlated with multiple indices of good health—better overall health and vitality, higher levels of self-rated health, normal cholesterol, lower body mass index and normal blood pressure—as compared to older individuals with lower glutathione levels.14

• Higher glutathione status and/or dietary intakes have been correlated with good cardiovascular,15 oral16,17 and eye health.18,19

• Glutathione supplementation may help increase levels of glutathione in certain circumstances associated with low glutathione status including cigarette smoking, heavy drinking, use of large numbers of prescription and non-prescription medications and chemotherapy.2

• Glutathione supplementation may help increase levels of glutathione in conditions associated with low glutathione status including obesity, type 2 diabetes, cardiovascular disease, kidney disease, Parkinson disease, lung disease, AIDS and other diseases.2 

Potential Benefits of Oral Supplementation

Modern diets are often devoid of glutathione due to the excessive intake of processed foods. Dietary intakes of glutathione among Americans have been measured in at least two studies. In the first, intakes ranged from a low of 3mg/day to a high of about 150mg/day, with a mean intake of 35mg/day.1 Another study found an even wider range of intakes among men—from 5mg to 242mg/day and 7mg to 96mg/day in women, with most people regardless of gender falling below 60mg/day.17 If the best diets provide close to 250mg/day and the mean intake is only 35mg, there is a considerable gap in much of the population.

Glutathione levels fluctuate diurnally with lowest levels found in the morning, which may present a window of vulnerability that could be addressed through increased oral intake. The morning shortfall becomes even lower with advancing age.22 Many millions of Americans have one or more dietary, lifestyle or physical factors that may increase their risk for low glutathione levels:23

• 77 million consume fewer than five fruits or vegetables a day

• 91 million are aged 55 and over

• 59 million currently smoke cigarettes

• 74 million have diabetes

• 110 million are overweight or obese

• 15 million chronically consume excessive amounts of alcohol Safety There have been no reported adverse reactions to supplemental glutathione taken orally, inhaled or used intramuscularly or intravenously.24 Doses of 3g have been used experimentally with no adverse effects.25

Rapid Screening Test for Adulteration of Dietary Supplement Ingredients

The FDA and media reports have identified an increasing incidence of adulteration concerns in dietary supplements. There have been 27 FDA-recorded product recalls from January 2010 to January 2011, demonstrating that deliberate adulteration is not an isolated problem. Many of the adulterants of concern are active pharmaceutical materials, added to products to “boost” their desired effect; products have been found to contain erectile dysfunction drugs, anabolic steroids and prohormones, and anorectics, diuretics and stimulants.

Controlled manufacturing processes, ethical business practices and strict quality control (QC) procedures can ensure that no adulteration is introduced during product manufacturing. However, raw materials used in dietary supplements are susceptible to deliberate adulteration.

There have been three instances of multiple product recalls for which a single raw material was found to be the source of adulteration.1 Most of the current adulterant testing procedures use expensive and timeconsuming techniques such as liquid chromatography-tandem mass spectrometry (LC-MS/MS) or gas chromatography- mass spectrometry (GC-MS).

These methods are not practical QC screening tools given the high cost of instrumentation, personnel and time. As a more practical alternative, a rapid technique was developed to screen raw materials for adulteration using Fourier transform infra-red spectroscopy (FTIR).

The method, “Rapid screening test for adulteration in raw materials of dietary supplements,” was published in the March 2011 edition of the peerreviewed journal Vibrational Spectroscopy.2 FTIR instrumentation is commonplace in production facilities, relatively inexpensive, simple to use and requires a considerably shorter run time than other techniques. Many of the adulterants of concern are active pharmaceutical materials, which provide a great deal of infrared (IR) spectral information. This feature allows the method to be functional across a wide variety of raw materials, and can be adapted to identify a broad range of adulterants.

Samples of materials were analyzed using Attenuated Total Reflectance (ATR)-FTIR (PerkinElmer FTIR Spectrum One), which is well suited for solid samples and fine powders. The FTIR-ATR test was designed to search for the IR features of adulterants in the spectra of raw materials. The screening method is easy and rapid to use, requires minimal sample preparation and is easily modified to analyze new raw materials or screen for new adulterants as they emerge.

The method is designed to automatically report a ‘Pass/Fail’ assessment in the PerkinElmer AssureID software package, requiring no data interpretation by the operator.

Since the raw materials and adulterants have distinct spectra, it is possible to identify peaks that will exist in the adulterants, but not the raw materials. The method is set up to determine the similarity between two spectra. Two spectra with very similar patterns will have a high match, whereas two spectra with dissimilar patterns will have a lower correlation. Thus, a sample that has been adulterated will contain additional peaks that are not present in untainted raw material. When an adulterated sample spectrum is compared to an unadulterated sample spectrum, the spectral patterns will not match, and a ‘fail’ report will be generated.

Method reproducibility and repeatability were good. A false negative error rate of only 0.5 percent was obtained during routing screening of 201 ingredients. A false negative is any sample passing the test, which should have failed. The method was designed under strict passing conditions to prevent false negatives. Any false positives require additional investigation.This adds a further layer of safety and assurance to the test. The false positive error rate for the 201 samples was 25 percent.

The limit of detectable adulterants in ingredients was found to be in the range of three to 10 percent (w/w), depending on the ingredient and adulterant.
A 3.0 percent (w/w) detection limit corresponds to 30mg/g of adulterant per sample. This detection limit would be unacceptable for finished product screening, and this method is limited in its applicability to finished product testing. However, it is appropriate for raw material screening. For example, if the finished product is a 1,000mg capsule that contains 100mg of raw material adulterated at 3.0 percent (w/w), the final product would contain 0.3 percent of the adulterant. This amount is well below the reported levels of adulteration found in finished products, which range from 1.46-50.66 percent (w/w).

Clinically Validated to Enhance the Absorption of Nutrients in Intestinal Cells

Sustainability of human life requires the availability of life-supporting essential nutrients to the trillion cells in the human body. Eating a balanced diet that contains all these essential nutrients is only the start as they must be broken down to the molecular level by the digestive process, and absorbed by intestinal cells before they become available to cells.

Much attention has been given to digestion as evidenced by the number of digestive enzymes as well as probiotic products on the markets. Yet, clinical studies and evidence indicate absorption is equally a serious, if not more serious, problem.

The most critical phase in the long and complicated nutrient uptake processes in the human body occurs at the final transportation and absorption phase, which truly decides how much of these nutrients will be available to the trillion cells in human body. The most balanced diet and complete digestion do not guarantee that these nutrients will be totally absorbed. Only when nutrients (except fatty acids) are absorbed (entered) into the intestinal cells are they retained in the body. Otherwise, they are expelled in a few hours.

And the key to enhance the absorption of any nutrient (except fatty acids) is to enhance the gene expressions of the particular mRNA and protein transporter that regulate its passage from the intestine to the inside of intestinal cells where they are collected and transported to the liver by portal vein for systemic distribution throughout the whole body.

Recognizing absorption’s critical role in overall health and well-being, and the serious validation in the effectiveness of absorption-enhancing products on the market, NuLiv Science International launched a major research effort in this area a decade ago. The result of such a long and intensive research effort is AstraGin™, a proprietary, all natural, plant-derived formulation consisting of highly fractionated Panax notoginseng and Astragalus membranaceus extracts using a proprietary pharmaceutical extraction and processing technology.

In over a dozen in vitro studies, AstraGin has demonstrated to significantly increase the absorption of amino acids, vitamins and other nutrients in Caco-2 cells, as well as elevated the cellular ATP level in HepG2 cells when compared to the control groups. The in vitro studies on AstraGin, which were carried out to a very rigorous standard, are similar to the in vitro study published in J. Agric. Food Chem., Vol. 55, No. 5, 2007 by T.C. Chang, et al., that was sponsored and funded by NuLiv Science International.

For example, Caco-2 cells, the gold standard used by all pharmaceutical companies to test new drug candidates, were used in all in vitro studies. The integrity of the Caco-2 cell monolayer and the full development of the tight junctions were monitored before every experiment by determining the transepithelial electrical resistance (TEER) of filter- grown cell monolayer by use of a commercial apparatus (Millicell ERS; Millipore, Bedford, MA). Only cell monolayer with TEER values of 400- 600Ùcm2 were used for experiments. Each absorption assay, such as the one on arginine, was verified by two independent studies of triplicate assays, so the dose-dependent steady-rate of absorption across the cell membrane from apical to basal layer could be calculated accurately and correctly to statistically significant levels (P values) of 0. 05 or even 0.01. 

These in vitro studies have demonstrated that AstraGin regulated the absorption of amino acids, such as arginine, and other nutrients in the Caco-2 (intestinal) cells by increasing and altering both the mRNA (by realtime quantitative PCR (Q-PCR)) and protein transporter (by Western Blot Assay using bicinchoninic acid (BCA) protein assay kit) gene expression levels of these nutrients. Consequently, there were no surprises that the actual arginine and other nutrient absorption assays also showed parallel corresponding increases.

AstraGin is currently used in protein powders and bars, meal replacements, supplements, sport nutrition by body builders, functional beverages and nutraceuticals, such as cardiovascular, energy and children supplements. It can be included in almost any functional food and dietary supplement to enhance the absorption of other ingredients in these products and make these products more effective.

Catotenoids in Focus: Lutemax 2020 Combines Lutein and Zeaxanthin for Sharper Results

carotenoids are pigments that provide bright coloration (reds, oranges and yellows) and strong antioxidant action.1 While most carotenoids are found only in plants, lutein and zeaxanthin isomers are two carotenoids that naturally accumulate in the macula of the eye and are thought to protect against age-related degenerative diseases such as age-related macular degeneration, or AMD.1,2 Lutein and zeaxanthin supply the eyes with a yellow color known as the macular pigment.9,13 

Mechanism of Action 

The mechanisms by which lutein and zeaxanthin isomers are thought to provide protection to the eye are through their roles as blue light filters and as antioxidants. These macular pigments display antioxidant properties, including the ability to quench singlet oxygen and inhibit the peroxidation of membrane phospholipids. The macula is especially exposed to high light intensity and the high concentration of xanthophylls may exert a protective role against oxidative damage.

The Need to Reach Efficacious Levels 

As a natural component of the aging process, levels of lutein and zeaxanthin in the eye decrease with age, leaving the eyes susceptible to impairment.3 Epidemiological studies indicate that a dietary intake level of lutein and zeaxanthin at ~6mg/day would help counter this natural decline and have a positive effect on AMD prevention.3 However, current estimates of dietary intake of lutein and zeaxanthin in the US are around 1-3mg/day4,5,6, far below the level needed for optimum eye health. Given that AMD strikes an estimated 7. 1 percent of Americans aged 50-59, 14. 4 percent of those aged 70-79, and a startling 35.4 percent of Americans aged 80 and above, providing a means of supplementing dietary carotenoid intake is a pressing concern for modern eye health.14 

The Case for Combining Lutein and Zeaxanthin

Many eye health ingredients supply carotenoids solely in the form of lutein, however, both lutein and zeaxanthin are vital to the health of the macula. A healthy human eye requires much higher concentrations of both.8,9 Zeaxanthin is isomeric with lutein. In the eye, lutein is present as a single stereoisomer, while zeaxanthin occurs primarily as a mixture of the 3R,3’R (i.e R. R Zeaxanthin) and 3R,3’S isomer (i.e R’S or meso-zeaxanthin). These three alltrans carotenoids are the major pigments in the retina.13 Healthy diets typically have a 5:1 ratio of lutein to zeaxanthin.7 But traditional lutein ingredients contain only a 5:0.2 ratio. This is important to know because the two key zeaxanthin isomers are present in significantly higher levels in some parts of the eye. Lutein’s essential, but these zeaxanthin isomers have a stronger antioxidant power and an ability to absorb additional harmful radiation, which is crucial.1,15,16,17 

Lutemax 2020 Represents a Significant Eye Health Innovation

To meet the need for an ingredient that delivers nutritionally relevant, enhanced levels of zeaxanthin isomers in addition to lutein, OmniActive introduced Lutemax 2020™ in late 2009. Lutemax 2020 delivers lutein and zeaxanthin isomers in significantly higher concentrations, for convenient and more beneficial nutrient availability for the eyes.

For a complete list of references, visit www.niemagazine.com.

As a natural component of the aging process, levels of lutein and zeaxanthin in the eye decrease with age, leaving the eyes susceptible to impairment. Epidemiological studies indicate that a dietary intake level of lutein and zeaxanthin at ~6mg/day would help counter this natural decline and have a positive effect on AMD prevention.

The Role of Natural Ceramides in Body Homeostasis and Skin Integrity

Ceramides are a class of naturally occurring lipids, known as sphingolipids, recognized for their properties in protecting the integrity of cell membranes in the body. These compounds are well-known to support the protective barrier in the skin against environmental stresses. What is less wellknown is that ceramides can also participate in structure and function of a wide range of tissues and organs in the body as well as the central nervous system.

Due to their biological importance, ceramides are ubiquitous in nature. Both eukaryotic (plants) organisms as well as prokaryotes (animals) contain sphingolipids, which are defined by a common structural feature, namely a backbone sphingosine (D-erythro-1,3- dihydroxy, 2-aminooctadec-4-ene) consisting of an 18 carbon lipid with a fatty acid attached by an amide bond. The sphingolipids of mammalian tissues include ceramides; sphingomyelins or sphingophospolipids; and cerebrosides, gangliosides and sulfatides collectively referred to as glycosphingolipids. Plants, fungi and yeast sphyingolipids, however, contain mainly ceramides, cerebrosides and phosphoinositides. The daily consumption of sphingolipids in a typical human diet is estimated at 0.3-0.4g/d, however there is no known nutritional requirement for sphingolipids.

Until recently, it was assumed that ceramides and other sphingolipids, predominantly found in the bilayer cell membrane, were functioning as structural elements. However, it was recently discovered that ceramides and sphingolipids can act as dynamic molecules that help in communication between cells and coordinate cellular physiology in the process called cellular signaling.

The most well-known functions of ceramides in cellular signaling involve regulating the differentiation, proliferation and programmed cell death or cellular apoptosis. Ceramides generated in the skin during cellular stress (injury or disease process) have been shown to activate important biological molecules that counteract skin injury. The signaling enacted by the ceramides also aid in healing by helping to form the skin protective barrier by potentially up-regulating the cellular membrane transport of ceramide building blocks such as glucosylceramides. The newly formed ceramides supply the protective layer of lipids in superficial layer of the skin to help protect against environmental elements and safeguard against loss of water through the skin.

Therefore, ceramides can signal and regulate their own synthesis and transport, as exemplified by skin ceramides.

The growing science of ceramides justifies its use as a nutritional supplement and skin care product. Vegetable ceramides are the preferred form in skin care due to their well-recognized food safety quality and excellent physical and chemical stability profile.

The biological role of vegetable ceramides in skin and hair care was successfully evaluated in the skin and hair (follicular) fibroblast model (in vivo and exvivo) and in clinical studies with ingestible and gluten-free wheat ceramides (Lipowheat®). A doubleblind, randomized, placebo-controlled study was carried out on 51 women aged 20–63 years with dry to very dry skin who received either 350mg of ceramide softgels or placebo for three months. Evaluation of skin hydration on legs, arms and face was assessed at baseline and at the end of the study.

The dermatologist, using dermatological scores (dryness, roughness, erythema), skin hydration measurement (corneometry) and self-assessment scores (Visual Analogue Scale: VAS), performed the assessment. Lipowheat demonstrated a statistically significant (p<.001) increase in skin hydration of

35. 1 percent compared to an increase of just 0.85 percent with placebo over the course of the three months daily administration. The 350mg capsules of Lipowheat oil were well tolerated with excellent compliance throughout of the study (Int J Cosmet Sci. 2011 Apr;33(2):138-43).

Boswellin PS

Boswellin® PS, representing a complete and full spectrum of bioactives is Sabinsa’s new proprietary extract of Boswellia serrata gum resin, standardized to suppress the proliferation in inflamed areas and prevent the break-down of inflammation affected connective tissues with no side effects like gastric irritation and ulcerogenic activity.

In India, the gum resin exudate of Boswellia serrata (Family-Burseraceae), vernacularly known as Sallaki, Salai guggal and Indian frankincense or Indian olibanum, in English, has been used in ayurveda for several inflammatory disorders. 1 Boswellia serrata in contemporary medicine is primarily used for joint health, as an anti-arthritic and antiinflammatory agent. Boswellic acids are reported to be non-competitive inhibitors of 5-lipoxygenase enzyme.
AKBBA has shown to be the most potent inhibitor of 5-lipoxygenase enzyme.2 

Boswellin PS (PS for Polysal™) contains the active Boswellic acids along with Polysal, a polysaccharide with proven anti-inflammatory activity. The uniqueness of this product lies in the fact that both the water-soluble Polysal and the water-insoluble boswellic acids have been isolated from the same plant Boswellia serrata by an innovative proprietary process. The water-soluble Polysal gets readily absorbed and initiates the anti-inflammatory action, while lipid-soluble boswellic acids provide sustained anti-inflammatory action that in combination with Polysal shows significant enhanced anti-inflammatory effect. Boswellin PS is an example of sensible blending of both water-soluble and water-insoluble fractions of Boswellia serrata to augment the anti-inflammatory response and derive maximum benefit in the management of pain and inflammation, and lacks precedence in alternative healthcare of recent times.

Boswellin PS has shown advantages in three areas, over conventional Boswellia serrata extracts that are standardized for one or more boswellic acids alone: enhanced water solubility; unique, two-stage release profile for actives that support immediate and sustained action; and enhanced activity against pro-inflammatory cytokines, which translates to added benefits in supporting joint health and mobility. In in vitro studies, and in animal models of induced inflammation tested with Boswellin (a conventional extract standardized for boswellic acids), Boswellin PS and Polysal, Boswellin PS was found to be more effective.

Mechanism of Action 

Boswellin PS has a well-defined mechanism of action. Both Boswellic acids and Polysal in Boswellin PS have anti-inflammatory activity and offer a two-pronged mode of action that effectively inhibits inflammatory insults. The effect can be measured by decreases in the levels of TNF-alpha (tumor necrosis factor, a cytokine), which plays a very important role in the pathogenesis of septic shock induced by LPS (lipopolysaccharides). Dysregulation of TNF production has been implicated in a variety of human diseases, including cancer. IL-â (interleukin-beta, a cytokine) features in physiological immune responses and in the development of various immunopathological disorders. Nitric oxide (NO) production is important in protecting vital organs against ischemic damage; however, uncontrolled production is associated with deleterious effects.

The anti-inflammatory potential of Boswellin and Boswellin PS were evaluated by flow cytometric studies. Boswellin PS inhibits pro-inflammatory cytokines, TNF-alpha, IL-1beta and inflammatory mediators like LTB4, PGE2 and nitric oxide in in vitro as well as in vivo preclinical systems. TNF-alpha is involved in immunopathological disorders causing systemic inflammation, thus, stimulating the acute phase inflammatory reaction. Inhibition of IL- 1beta by Boswellin PS demonstrates its inhibitory properties on immune related inflammatory diseases. The various studies done on Boswellin PS indicate that it has a better potential as an antiinflammatory nutrient when compared to its constituents. Boswellin PS decreased the pro-inflammatory markers TNF-á, IL-â and NO radical better than Boswellin.3 As Boswellin PS inhibits the same marker proteins responsible for the development of various inflammatory disorders through its broad spectrum anti-inflammatory activity, it can find potential use in the management of various inflammatory disorders like chronic and ulcerative colitis, Crohn’s disease, asthma, peritumoral brain edemas and inflammatory bowel syndrome besides being a promising candidate in managing rheumatoid arthritis and osteoarthritis.

Both Boswellic acids and Polysal were found to have good safety profile. As per OECD guidelines, acute oral toxicity (LD0) for Boswellic acids was found to be 2,000mg/kg b.w. Acute oral toxicity (LD0) for Polysal™ was also found to be 2,000mg/kg b.w. Boswellin and Polysal are trademarks of Sabinsa Corporation. U.S. and International patents on Boswellin PS are pending.

Probiotic Supplement Reduces Atopic Dermatitis in Preschool Children: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

The burden of atopic disorders including atopic dermatitis (AD) is significant and far-reaching. AD is a common inflammatory skin disorder with a prevalence ranging from 15.6 percent in Europe to 17.2 percent in the U. S., and a steady trend towards increase. The disease often presents in early childhood and persists into adult life in 60 percent of patients—affecting their quality of life as well as those of their caretakers. Complementary and alternative therapies are commonly used because of concerns about potential adverse effects of conventional therapies and lack of response to prescribed medications. Despite the promising results reported with probiotics, herbal medicines and biologic products, the clinical efficacy of such alternative therapies remains to be determined.

The therapeutic use of probiotics has attracted considerable attention after publication of the hygiene hypothesis (BMJ 1989; 299:1259-60). Several clinical studies have demonstrated mild to complete resolution of AD following treatment with probiotics, while other studies have suggested that the effect is limited to selected children with atopy or is undetectable. A recent systematic review of the available evidence called for further clinical trials with new probiotic formulations.

This study was designed to determine the clinical efficacy and impact of a probiotic product (DDS® Junior from UAS Laboratories, Inc.) on peripheral lymphocytes subsets in preschool children with moderate to severe AD. A total of 90 children, ages 1-3 years suffering from moderate-tosevere AD were randomly divided into two groups to receive either the probiotic product or the placebo. Parents administered the doses twice per day to provide a total of 10 billion CFU/g of a combination of L. acidophilus DDS®-1 and B. lactis UABLA-12 with fructooligosaccharides (DDS Junior) for eight weeks.

The primary outcome measure was percent change in scoring of atopic dermatitis (SCORAD) index at week eight. Secondary outcomes were changes in infant dermatitis quality of life (IDQOL), dermatitis family impact (DFI) scores at weeks two, four and eight frequency, and amount of topical corticosteroid used and absolute number and percent of peripheral blood lymphocyte subsets at week eight. Children displayed a progressive decline in SCORAD indexes reaching significant difference at week four in both groups; however, children receiving probiotics experienced a more rapid decline.

At week eight, children receiving the probiotic product (DDS Junior) demonstrated 33.7 percent decrease in SCORAD versus 19.4 percent in the placebo group. Other outcome measures included a 33 percent increase in IDQOL, 19 percent in placebo and a 34.4 percent increase in DFI in the probiotic group versus 23.8 percent in placebo. Use of topical corticosteroid averaged 7.7g less in probiotic patients. Patients with active AD had a reduced percentage of CD3 and CD8 peripheral lymphocytes and increased CD4 and CD25 counts. Hypothetically, the recovery from AD due to use of probiotics may be accompanied by normalization of CD3, CD4, CD8 and CD25 numbers. The study showed a significant correlation between reduction in CD4 and CD25 percent/absolute number and SCORAD values at week eight in the probiotic group.

The research showed that the administration of DDS Junior containing L. acidophilus DDS-1, B. lactis UABLA-12 and fructooligosaccharide was associated with significant clinical improvement in children with AD, and corresponding lymphocyte subset changes in peripheral blood.