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2014 Science Of Supplements

Colorcon
 
Kaneka

Since 2002, Nutrition Industry Executive’s Science of Supplements section has been offered 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 the research that substantiates the safety and efficacy of their branded ingredients, products and services.

These companies have responded to this opportunity with information about the health concerns their products are intended to address, histories of nutrients behind their ingredients and details of research that has been carried out. In order to bridge the gap between interested parties and those participating in this section, we’ve also provided company addresses, phone numbers, and e-mail and website addresses to make obtaining additional information as easy as possible. 

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

Biotron Laboratories ………………………………..42
Certified Nutraceuticals, Inc. ……………………43
Chemi Nutra …………………………………………..44
Ecuadorian Rainforest, LLC. ……………………..45
GC Rieber Omega-3 Concentrates …………..46
Gencor ………………………………………………….47
HerbaKraft Inc. ……………………………………….48
Kyowa Hakko USA ………………………………….49
Nutegrity………………………………………………..50
NutriScience Innovations, LLC ………………….51
PLT Health Solutions, Inc. …………………………52
Sabinsa Corp. …………………………………………53
Stratum Nutrition/ESM Technologies…………54
U.S. Pharmacopeial Convention (USP) ……….55
Verdure Sciences ……………………………………56

Non-GMO Project

Biotron Laboratories

750 N. 1250 W. Centerville, UT 84014 Phone: (801) 298-8438 • Fax: (801) 298-8800 Email: gameil@biotronlabs.com Website: www.biotronlabs.com

Ferractiv: A Unique Iron Preparation

Perhaps the single most important factor for women considering supplementary iron is the frequent occurrence of uncomfortable side effects such as stomach upset, bloating and nausea.

Ferractiv® iron supplement powder is a unique, iron multi-amino acid chelate ingredient that has been clinically proven to be well tolerated. A study of 60 healthy, premenopausal women in a randomized, double blind, placebo-controlled trial showed a statistically significant reduction in side effects when given an equivalent amount of iron as Ferractiv as compared to ferrous sulfate, one of the most commonly used and well-absorbed iron salts.1

Additionally, in-vitro experiments using a novel and highly sensitive iron absorption assay, developed by Dr. Ray Glahn and colleagues at the USDA (U.S. Department of Agriculture) and Cornell University Department of Food Science, have shown Ferractiv iron supplement to be highly bioavailable—meeting or exceeding the benchmark for bioavailability (ferrous sulfate-heptahydrate) in this model system.2

This in-vitro work has been extended to the clinic, where large scale (n=450) trials in pregnant, anemic women demonstrates the performance of Ferractiv iron supplement. Women receiving Ferractiv-containing capsules responded more quickly, with fewer complaints of discomfort, when being treated for iron deficiency anemia by three separate clinical measurements. Importantly, these benefits were realized at a comparable cost on a per-dose basis when compared to frequently used alternatives.3

Finally, Ferractiv has been studied at the atomic level in collaboration with the Canadian Light Source (CLS) at the University of Saskatchewan in Saskatoon, Canada. The CLS is Canada’s national synchrotron. This world-class research facility enables scientists and engineers to study the microstructure and chemical properties of materials. Ferractiv was analyzed using the Hard X-ray Micro Analysis Beamline 6ID. The collaboration between Biotron and the CLS has demonstrated a quantitative difference between both the bonding energy and bond distances of the atomic structures within the multiple amino acid matrix of Ferractiv.4

This data enables a definitive distinction to be made between this fully reacted mineral chelate and other unreacted physical blends or irritating, low value inorganic salts. Taken together, these data demonstrate that Ferractiv is a safe, economical, well-tolerated, highly bioavailable and unique iron-preparation—the ideal iron ingredient for safe, gentle and effective supplementation.

References: 1 Fouad, G.T., Evans, M., Sharma, P, Baisley, J, Crowley, D and Guthrie, N. A Randomized, Double Blind, Clinical Study on the Safety and Tolerability of an Iron Multi-Amino Acid Chelate Preparation in Premenopausal Women. J Diet Supp. (2013) 10(1); 17-28.

2 Glahn, R.P., Lee, O.A., Yeung, A., Goldman, M.I., Miller, D.D. Caco-2 cell ferritin formation predicts nonradiolabeled food iron availability in an in vitro digestion/Caco-2 cell culture model. J. Nutr. 1998 Sep;128(9):1555-61.

3 Abdel-Lah, M., Rasheed, Sl, Hassan,ll, El-sayed, A. Iron chelated amino acid therapy versus oral iron therapy for the treatment of iron deficiency anemia with pregnancy. The J Egyp Soc of Obst and Gyn. 2006; 32 (4,5 &6): 419-428.

4 Data on file, Biotron Laboratories, Inc. Centerville, Utah, 84104 (December, 2008). “X-ray Absorption Spectroscopic Measurements of Cr, Fe and Cu in Dietary Supplements.”

Certified Nutraceuticals, Inc.

41785 Elm St., Ste. 301 Murrieta, CA 92562 Phone: (951) 600-3899 • Fax: (951) 600-8676 Email: info@certifiednutra.com Website: www.certifiednutra.com

kollaGen IVX.HEM: Safe, Efficacious for Joint & Connective Tissue Disorders

Millions of adults in North America alone have a medical condition relating to a skin disorder, joints and/or connective tissues, osteoarthritis, fibromyalgia and lupus. The options available to treat the symptoms associated with arthritis, joint deterioration and other related diseases/conditions are limited and come with side effects. While the majority of past/present treatments (acetaminophen, ASA, Cox 2s, NSAIDS, narcotics, steroids) alleviate the associated symptoms (pain, inflammation), they have had limited success and some varying degree of side effects.

To that end, Certified Nutraceuticals developed kollaGen IVX.HEM™ – Hydrolyzed Egg Membrane, a protein characterized by a developmentally advanced proportion of collagen that is effectively matched to skin. It elevates the fibroblasts activity and promotion, stimulating their growth and strengthening the matrix. Fibroblasts are morphologically heterogeneous with diverse appearances depending on their location and activity. The location and timing of cellular differentiation is stringently controlled for adequate organ formation. A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen. Fibroblasts make collagens, glycosaminoglycans, reticular and elastic fibers, glycoproteins found in the extracellular matrix and cytokine TSLP. Tissue damage stimulates fibrocytes and induces the mitosis of fibroblasts.

kollaGen IVX.HEM contains several bacteriolytic enzymes and other components that alter the effect of heat-resistant gram-positive and gram-negative pathogens, increasing the skin’s ability to withstand a variety of inflammatory processes. It also contains very powerful compounds including: a complex of glycosaminoglycans such as glucosamine, chondroitin and hyaluronic acid, elastin, collagen, desmosine, isodesmosine and transforming growth factor, among others. The compounds are proven to be of use for pain management associated with joint disease, due to the distinctive concentration of the potent, natural compounds in the HEM.

A kollaGen IVX.HEM supplement was given to 20 men and woman during a 60-day clinical trial with the goal to examine the effectiveness of this substance on patients with symptoms associated with osteoarthritis and related inflammatory diseases/conditions, which could prove to be far reaching.

Targeted Clinical Response Results

Supplementation with kollaGen IVX.HEM produced a significant treatment response at seven days for flexibility (74.5 percent increase; P = 0.035) and at 60 days for general pain (91.7 percent reduction; P = 0.006), flexibility (70.6 percent increase; P =0.006) and range of motion associated pain (77.3 percent reduction; P = 0.020). There were no adverse events reported during the study and it was reported that the treatment was well tolerated by study participants.

The graph clearly illustrates the pain reduction level on kollaGen IVX.HEM. In the single-arm pilot trial, the percentage of the study participants experienced greater flexibility and superior free movement, as well as better range of motion for unstable and painful areas of their bodies. Another area of clinical importance was that more than 70 percent of the trial participants experienced an exemplary improvement in their pain and flexibility at 14 days into the trial.

The results from this human clinical trial demonstrate that kollaGen IVX.HEM is a practical treatment option for the overall management of joint and connective tissue disease, symptoms and related superfluous side effects. The study, in particular, noted an excellent response for participants suffering from osteoarthritis. A clinical trial dosage of 500 mg taken daily had a rapid response effect within a seven-day period and more than 70 percent at day 14. The participants’ clinical picture continued upward to 60 days into the trial, receiving the full weight of the substance’s capabilities to reduce pain, inflammation and regional swelling to some degree. The participant’s quality of life had increased upwards of 80 percent after the conclusion of the trial. Another intriguing aspect was that the blood glucose levels of two new participants started to normalize after half way into the trial. Researchers stated this is an exciting discovery that clearly needs further examination to establish how great the margin of treatability actually is.

kollaGen IVX.HEM is a viable option for the treatment/management of joint and connective tissue disease/disorders, marked pain syndrome with a substantial reduction of symptoms. According to Certified Nutraceuticals, trial participants and clinical team exhibited or observed no side effects or allergens (as screened prior) throughout the 60-day trial, indicating not only efficacy but safety as well.

References:

Mortec Scientific Group, Cambridge, Ontario, Canada. Effects of Hydrolyzed Egg Membrane on Human, January 2014.

Wong M, Hendrix MJC, Vonder Mark K, Little C, Stern R. Collagen in the eggshell membranes of the hen. Devel Biol. 104:28-36 (1984).

Arias JL, Fernandez MS, Dennis JE, Caplan AL collagens of the chicken eggshell membranes. Connect Tissue Res. 26:37-45 (1991).

Greco RM, et al. Hyaluronic acid stimulates human fibroblast proliferation within a collagen matrix. J Cell Physiol. 177(3):465-473 (1998).

Chemi Nutra

4463 White Bear Pkwy., Ste. 105 White Bear Lake, MN 55110 Phone: (866) 907-0400 Email: chase@cheminutra.com Website: www.cheminutra.com

Mediator PA: An Alternative for Muscle Mass Loss Health Concerns

Signaling by the mammalian target of rapamycin (mTOR) has been reported to be necessary for mechanical load-induced growth of skeletal muscle (muscular hypertrophy). Several studies indicate that both phospholipase D (PLD) and the lipid second messenger phosphatidic acid (PA) play critical roles in the mechanical activation of mTOR signaling. Interestingly, it has been shown that an elevation in PA concentration is sufficient for the activation of mTOR signaling.

Following extensive investigation into the role of PA, Chemi Nutra discovered how it could significantly influence load-induced growth of skeletal muscle via the mTOR pathway. In addition, it was discovered that orally ingested PA, in fact, exhibited noticeable effects on lean muscle mass and strength development, especially when adequate amounts of protein, administered within the anabolic window, were provided to exercising individuals. As a result of these discoveries, Mediator® PA will find major application in finished nutritional products targeted to sports nutrition, healthy aging, where age-related muscle loss (sarcopenia) is now a major concern, and likely also to ill/bedridden (cachectic) individuals, where loss of lean mass is a health concern.

Thus far, two human efficacy studies have been completed to further investigate PA. The first study1 was performed at the University of Central Florida, Orlando and was led by Jay Hoffman, PhD. The study involved 16 men, aged 19 to 27 years, who all performed the same four-day per week, split routine resistance training program for eight weeks. Both subject groups were provided a 36 g amino acid and collagen protein blend, and one group was given Mediator PA (750 mg PA active), while the other group was given a placebo, on a daily basis. Body composition was determined using whole body dual energy X-ray absorptiometry (Lunar Corp. DEXA), which provided values of total body fat and non-bone lean tissue. In addition, skeletal muscle architecture was assessed in subjects’ self-reported dominant leg using B-mode ultrasound imaging (GE LogIQ P5). Here, vastus lateralis muscle thickness and pennation angle were measured during each test period. Dietary records were maintained by subjects throughout the study period, to include between-meal and late-evening snacks.

Results showed the Mediator PA group had a 12.7 percent increase in squat strength vs. a 9.3 percent increase in squat strength for the placebo group, which was a 37 percent strength increase difference for the PA subjects. The PA group had a 5.1 percent increase in bench press strength vs. a 3.3 percent increase in bench press strength for the placebo group, which was a 55 percent strength increase difference for the PA group. Finally, the PA group had a 2.6 percent increase in lean muscle mass.

A second study2, performed at the University of Tampa’s (FL) Department of Health Sciences and Human Performance Lab with corresponding author Jacob Wilson, PhD, showed even greater results. In this randomized, double-blind study, subjects performed a three day per week resistance training regimen for eight weeks. Some subjects consumed 750 mg of PA, while others received a placebo. PA supplementation resulted in significantly greater increases in muscle cross sectional area and lean body mass compared to the placebo. The PA subjects gained 5.3 lbs. of lean muscle mass compared to the 2.6 lbs. that the placebo gained. This translates to a 200 percent increase in lean muscle mass gain for individuals training and supplementing with PA versus training without. Consumption of PA allowed the subjects to gain 47 percent in bench press strength versus the placebo group; and PA consumption allowed subjects to gain 68 percent more cross sectional area in their large quadriceps muscle versus the placebo group. Perhaps equally surprising are findings in fat mass; subjects who consumed PA lost more than double the amount of fat mass that the placebo group did. Over the eight weeks, PA subjects lost 2.9 lbs. of fat mass versus 1.1 lbs. for the placebo group.

As a result of these impressive findings, Chemi Nutra has filed a series of patents for PA’s use in supplement and functional food products (U.S. Patent Application Number 13/373,649). The company plans to further investigate the use of PA in upcoming studies; where dosage, protocol and population changes.

References:

1 Hoffman J., Stout J., Williams D., Wells A., Fragala M., Mangine G., Gonzalez A., Emerson N., McCormack W., Scanlon T., Purpura M., Jäger R. Efficacy of phosphatidic acid ingestion on lean body mass, muscle thickness and strength gains in resistance-trained men. J Intl Society of Sports Nutrition. 2012, 9:47. Doi: 10.1186/1550-2783-9-47.

2 Unpublished; results presented at the annual International Society of Sports Nutrition (ISSN) conference in June 2013.

Ecuadorian Rainforest, LLC

25 Main St., Bldg. 6 Belleville, NJ 07109 Phone: (973) 759-2002 • Fax: (973) 759-3002 Email: info@intotherainforest.com Website: www.intotherainforest.com

Marine Ingredients: Delivering Vitamins & Minerals Essential for Optimal Health

Man has been tilling the earth for centuries, using the ground’s fertile soil to grow nutrient-dense foods needed to sustain life and civilized society as we know it. Much importance has been placed on foods that can be grown in the ground, from staples like grain, to the more exotic, like superfruits that include pomegranates and mangoes. And, until recently, a large portion of the planet has mostly ignored for its own plants: the world’s oceans. Ecuadorian Rainforest, LLC, believes that the species found in these vast oceans will be an important staple in the diets of consumers who are conscious of their nutritional needs.

Many seaweed and algae varieties contain significant quantities of the necessary vitamins and minerals that are essential for optimal health. Science has been steadily uncovering the potential in marine ingredients and what it can mean for the diets of the people on earth. In one study, researchers measured the therapeutic properties of seaweed. Researchers have focused on the potential benefits of sulfated polysaccharides, found in various species of seaweed. The sulfated polysaccharides are effective in a multitude of ways, one being in antioxidant properties. Antioxidants are molecules that may help combat free radicals, agents found in the body that may accelerate aging.

Seaweed has shown potential to be used as an anti-inflammatory agent, as well. In a study published in August 20111, researchers studied the effects of sulfated polysaccharides found in Solieria filiformis. They discovered that the sulfated polysaccharides had an anti-inflammatory effect in experimental models of nociception in mice. In another study2, researchers tested crude polysaccharides from a brown alga named Turbinaria ornata against carrageenan-induced paw edema in rats. Rats given an oral dosage of the sulfated polysaccharides showed reduced paw edema, another promising sign showing that sulfated polysaccharides found in seaweed may be a natural way to combat inflammation.

Algae are known as one of the best sources of nutrition available in the world. Algae are organisms that contain chlorophyll and host many necessary nutrients. Algae can have a wide array of benefits that include carotenoids, phenolic compounds, phycobiliprotein pigments, polysaccharides and unsaturated fatty acids, according to research published in 2011.3

The study partially focuses on the antioxidant properties of algae. It suggests that sterols such as gramisterol and sitosterol were “inhibited oxidation by acting as hydrogen donors.” That means algae are able to resist the damage caused by oxidation. The nutrients protecting algae from oxidation, including carotenoids, vitamin C, polyphenols and phyco-biliproteins, can be a huge benefit for consumers who are looking to help to combat the problems of oxidation.

“The ocean hosts integral nutrients for our diets,” said Steve Siegel, vice president of Ecuadorian Rainforest. “Each variety of seaweed and algae has distinct nutritional properties. They cover almost every nutritional base imaginable and science is finally catching up. Soon, marine ingredients such as seaweed and algae will become indisposable parts of consumers’ diets. That is why we have such a robust selection of marine ingredients.”

These studies show the nutritional value of marine ingredients and how they can play an important role in the overall health of consumers looking for nutrient-dense ingredients. Ecuadorian Rainforest offers a wide choice of seaweed and algae ingredients collected from South America and beyond.

To find the right marine ingredients for a company’s product, visit Ecuadorian Rainforest at www.intotherainforest.com to explore its catalog.

References:

1 Ianna Wivianne Fernandes de Araújo, Edfranck de Sousa Oliveira Vanderlei, José Ariévilo Gurgel Rodrigues, Chistiane Oliveira Coura, Ana Luíza Gomes Quinderé, Bruno Pedrosa Fontes, Ismael Nilo Lino de Queiroz, Roberta Jeane Bezerra Jorge, et al. Effects of a sulfated polysaccharide isolated from the red seaweed (Solieria filiformison) models of nociception and inflammation. Carbohydrate Polymers. August 30, 2011.

2 Ananthi S., Raghavendran HR, Sunil AG, Gayathri V, Ramakrishnan G, Vasanthi HR. In vitro antioxidant and in vivo anti-inflammatory potential of crude polysaccharide from Turbinaria ornata (marine brown alga). Food and Chemical Toxicology. January 2010.

3 Emad A Shalaby. Algae as promising organisms for environment and health. Plant Signal Behav. September 2011; 6(9): 1338-1350.

GC Rieber Omega-3 Concentrates

Novel Ingredient Services (Exclusive U.S. Distributor) 10 Henderson Dr. West Caldwell, NJ 07006 Phone: (866) 668-3550; (973) 808-5900 Fax: (973) 808-5959

High-Potency DHA Concentrates Benefit Brain, Vision Health at Every Stage

Omega-3 fatty acids rich in DHA have been shown to help promote proper development or maintenance of brain and vision health during all stages of life—from conception to old age. High-potency DHA concentrates—such as GC Rieber’s 70 DHA Ultra TG, one of the industry’s first DHA concentrates with 90 percent total omega-3s—not only offer greater efficacy, they enable formulators to deliver scientifically relevant amounts of DHA in a single dose—even in multi-ingredient formulas.

Pregnant Women

During pregnancy, DHA plays an important role in fetal development, supporting optimal infant brain, eye and nervous system development. It is particularly important during the third trimester when significant brain and organ growth occur. Since babies in utero cannot efficiently produce DHA, they must obtain this vital nutrient through their mothers’ placentae. Studies indicate that high-potency DHA may also help lengthen the gestation period, as well as support mood and mental health during pregnancy.

Nursing Mothers & Infants

After birth, DHA content of the infant’s brain triples during the first three months, and significant brain, eye and nervous system development continues throughout the first two years of life. At this stage, babies rely on their mothers’ supply of DHA (obtained through breast milk). The March of Dimes and National Institutes of Health suggest that women who breastfeed should get 200 to 300 mg of DHA daily, while some research studies recommend as much as 400 mg.

Children

DHA is important for children’s health, particularly cognitive development. From birth to 5 years of age, a child’s brain triples in mass, and the growing body depends on omega-3s to support normal cognitive function, brain and eye development. Recent clinical evidence shows that dietary intake of high-potency DHA may increase mental and visual performance and positively impact behavior and learning ability in young children.

Teens

The human brain grows and develops throughout adolescence, so omega-3s—especially high-potency DHA—play vital roles in teenagers’ learning, cognitive behavior and visual acuity.

Adults & Seniors

In adulthood, the goal is to maintain brain and vision health, and stave off the decline that frequently accompanies old age. Recent research suggests that high-potency DHA may help protect adult eyes and have a positive effect on age-related cognitive decline.

GC Rieber’s ultra-pure, high-potency DHA concentrates, available in 60 percent and 90 percent natural triglyceride (TG) forms, as well as popular ethyl ester (EE) forms, can be quickly and cost-effectively customized to meet unique structure/ function objectives for dietary supplements, functional foods and beverages, nutraceuticals, pharmaceuticals or medical foods. The ingredient is exclusively available through Novel Ingredient Services.

References:

Conquer. Fatty acid analysis of blood plasma of patients with Alzheimer’s disease, other types of dementia and cognitive impairment. Lipids. 2000, 35.12:1305-12.

Kalmijn. Dietary fat intake and the risk of dementia and cognitive decline: a review of clinical and epidemiological studies. Aging. 2000, 4:202-7.

Lauritzen. Maternal fish oil supplementation in lactation: effect on developmental outcome in breastfed infants. Reproduction Nutrition Development. 2005, 45(5):535-47.

Lukiw. Decosahexaenoic acid and the aging brain. Journal of Nutrition. 2008, 138(12):2510-4.

McCann. Is docosahexaenoic acid, an n-3 long-chain polyunsaturated fatty acid, required for development of normal brain function? An overview of evidence from cognitive and behavioral tests in humans and animals. The American Journal of Clinical Nutrition. 2005, 82:281-295.

Montgomery. Low Blood Long Chain Omega-3 Fatty Acids in UK Children Are Associated with Poor Cognitive Performance and Behavior: A Cross-Sectional Analysis from the DOLAB Study. PLoS ONE. 2013, 8(9): 10.1371.

Ryan. Assessing the effect of docosahexaenoic acid on cognitive functions in healthy, preschool children: a randomized, placebo-controlled, double-blind study. Clinical Pediatrics. 2008, 47(4): 355-62.

Stonehouse. DHA supplementation improved both memory and reaction time in healthy young adults: a randomized controlled trial. The American Journal of Clinical Nutrition. 2013, 97(5):1134-43.

Terano. Docosahexanoic acid supplementation improves the moderately severe dementia from thrombotic cerebrovascular disease. Lipids. 1994, 34 (Suppl):S345-6.

Yurko-Mauro. Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimer’s & Dementia. 2010, 6(6):456-64.

Gencor

19700 Fairchild Rd., Ste. 380 Irvine, CA 92612 Phone: (949) 502-5760 • Fax: (732) 875-0306 Email: info@gencorpacific.com Website: www.gencorpacific.com

ActivAMP: To Combat a Sedentary Lifestyle?

By Dr. Paul Clayton, Gencor Chief Scientific Advisor

Physical activity leads to multiple health improvements via the master metabolic regulatory enzyme 5’ adenosine monophosphate-activated protein kinase (AMPK). Broadly, AMPK determines whether available energy is utilized to meet immediate requirements, or stored for future use. Aerobic exercise generates hypoxia and increased cAMP in skeletal muscle. This activates (phosphorylates) AMPK, which triggers a coordinated cascade of positive metabolic responses.1

Firstly, activated AMPK interacts with another gene called MTOR to stimulate autophagy in muscle.2 Old mitochondria and contractile proteins are broken down, recycled and replaced with new ones. In favorable nutritional conditions3, exercise creates positive changes including increased muscle mass, improved capillary networks, more efficient contractile mechanisms,4 mitochondrial neogenesis and increased GLUT4 receptors on muscle cell membranes.5

These changes increase the muscle’s ability to carry out oxidative phosphorylation (muscle gets fitter), and enhance insulin sensitivity. Increased expression of muscle LPL improves plasma lipid profiles. Activated AMPK also increases fat burning via beta oxidation,4 and inhibits both cholesterol synthesis by down-regulating HMG CoA reductase6, and fat formation by down-regulating acetyl CoA carboxylase.

The net effects of this AMPK-induced cascade include improved muscular performance, visceral and other fat loss, and the reversal of metabolic senescence.7,8

New Ways to Activate AMPK

There is a second pathway to AMPK activation via resistance exercise, which up-regulates genes, which code for stress-inducible proteins called sestrins.9,10 These are analogous to the HSP’s (heat shock proteins) and AMP’s (anti-microbial proteins), and appear to be induced by physical stresses detected by transponders in muscle and bone.

Gymnestemma pentaphyllum, an herb traditionally used as a tonic for the frail and elderly, reproduces many of the benefits of exercise. Extracts of this herb were found to activate AMPK, presumably via sestrin up-regulation; and an extract of Gymnestemma pentaphyllum standardized to its actives, saponins known as damulins,11 has been intensively studied. The extract is called ActivAMP.

Pre-Clinical

ActivAMP exerted the same effects in ob/ob mice as the herb did in humans, including reduction of visceral fat.12 The saponins Damulin A and B were potent AMPK activators, considerably more so than AICAR, a synthetic thought to have won several Tours de France before it was banned.13,14

Clinical

Eighty subjects with BMI 25 to 30 were randomized to active or placebo and treated for 12 weeks.8 The active group received 450 mg Activ-AMP/day. Total abdominal fat area, body weight, body fat mass, percent body fat, and BMI were significantly decreased (p=0.044, p<0.05, p<0.0001, p< 0.0001, and p< 0.05, respectively) in the active group compared to placebo. Reduced visceral adiposity was particularly marked, as it is following exercise (see figure). There were no safety issues.

Summary

ActivAMP activates the metabolic master switch AMPK, and replicates the metabolic and health benefits of exercise.* It also has a role in sports and athletics, where its ability to improve muscle fitness is creating intense interest in professional circles.* Gencor is launching ActivAMP this year.

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.”

References:

1 Chau JY, et al. PLoS One. 2013, 8(11):e80000.

2 Egan B, et al. Cell Metab. 2013, 17(2):162–184.

3 Menendez JA, et al (2013). Cell Cycle. 12(4):555-78.

4 Baar K. Med Sci Sports Exerc. 2006, 38(11):1939–1944.

5 Burcelin R, et al. J Clin Invest. 2003, 111:1555–1562.

6 Davies SP, et al. Eur J Biochem. 1992, 203:615–623.

7 Calabrese V, et al. Mol Aspects Med. 2011, 32:279–304.

8 Park SH, et al. Obesity (Silver Spring). 2014, (1):63-71.

9 Lee JH, et al. Cell Metab. 2013, 18(6):792-801.

10 Lee JH, et al. Cell Metab. 2012, Sep 5;16(3):311-21.

11 Razmovski-Naumovski V, et al. Phytochem Rev. 2005, 4:197–219.

12 Gauhar R, et al. Biotechnol Lett. 2012, 34(9):1607-16.

13 Benkimoun P. BMJ. 2009, 339:b4201.

14 Private communications.

HerbaKraft Inc.

121 Ethel Rd. W., Unit 6 Piscataway, NJ 08854 Phone: (732) 463-1000 Fax: (732) 463-3336 Website: www.herbakraft.com

Beneficial Effect of Eurycoma longifolia on Men’s Health

By Vinod Khanijow and Dipanwita Dutta, PhD

In our daily routine, we are invaded by several chemicals mainly through food. Demand for growing more food in shorter duration of time than normal is leading to the usage of hormones, pesticides and other chemicals resulting in critical health effects. Infertility in males due to hormonal imbalance is now emerging as a major concern. These hormonal disturbances in men mostly lead to infertility due to low plasma levels of testosterone or gonadotropins or high plasma levels of estrogen.1 A decrease in testosterone level might result in low libido, erectile dysfunction, enlarged prostate, muscular weakness, risk for heart disease, stroke, type 2 diabetes, osteoporosis, depression and Alzheimer’s disease.2

Eurycoma longifolia, a Malayasian herb also known as tongkat ali or Long Jack, is known as a natural treasure there. The roots of Eurycoma longifolia are been known in traditional medicine to cure sexual dysfunction along with other uses as antipyretic, antimalarial, antibiotic and anti-diabetic properties.

The pharmacological activity of roots of Eurycoma longifolia is attributed by various quassinoids, a group of compounds classified as triterpenoids. Other active compounds include squalene derivatives, alkaloids like beta-carboline, tirucallane-type triterpenes.3,4 Eurycomanone, a major quassinoids demonstrated significant increase in spermatogenesis.5 Clinical trial with Eurycoma longifolia demonstrated significant increase in sperm concentration, semen volume, sperm motility and percentage of morphologically normal sperm.6

In a recent clinical trial, a randomized, double-blind, placebo-controlled and parallel group studies, Eurycoma longifolia showed improvements in libido and sexual performance.7

Norhazlina Abdul Wahab et al, 2010 with their study showed that Eurycoma longifolia appears to enhance virility and sexual performance in males by increasing the testosterone level.8,9 In a separate study, similar observation was noticed on treatment of Leydig cells with Eurycoma longifolia enhanced testosterone steroidogenesis by inhibiting aromatase conversion of testosterone to estrogen.5 Root extract of Eurycoma longifolia also demonstrated dose dependent recurrent and significant increase in the episodes of penile reflexes by increases in quick flips, long flips and erections of the treated male rats.10 It has been confirmed that Eurycoma longifolia elevates levels of free testosterone naturally by affects the LH/FSH feedback loop to improve the production of all of the androgens.

In a 28-days toxicity study, oral administration to mice at dosage 3,500 mg/kg body weight showed no sign of death nor any sign of intoxication.

Based on all scientific evidences, Eurycoma longifolia has a series of implications for the maintenance of men’s health. HerbaKraft’s lyophilized standardized LJack obtained from Malaysian Molson forest that helps not only in maintaining normal testosterone level, but also helps in weight management and to decrease body fat.

References:

1 Pinto ME et al. Exposure of young rats to high estrogen doses leads to degeneration of elongated spermatids. Tissue Cell. 2008, 40:31-42.

2 Shabsigh R. The effects of testosterone on the cavernous tissue and erectile function. World Journal of Urology. 1997, 15; 21-26.

3 Ang H et al. Eurycolactones A-C, novel quassinoids from Eurycoma longifolia. Tetrahedron Lett. 2000, 41; 6849-6853.

4 Le-Van-T et al. Constituents of Eurycoma longifolia Jack. J Org Chem. 1970, 35; 1104-1109.

5 Low BS, et al. Eurycomanone, the major quassinoid in Eurycoma longifolia root extract increases spermatogenesis by inhibiting the activity of phosphodiesterase and aromatase in steroidogenesis. J Ethnopharmacol. 2013, 26; 149(1):201-7.

6 Bin M I et al. Eurycoma longifolia Jack in managing idiopathic male infertility. Asian Journal of Andrology. 2010, 12; 376–380.

7 Ismail S.B et al. “Randomized clinical trial on the use of PHYSTA freeze-dried water extract of Eurycoma longifolia for the improvement of quality of life and sexual well-being in men,” Evidence-Based Complementary and Alternative Medicine. 2012, 10; 2012.

8 Ang H H et al. Eurycoma longifolia Jack enhances sexual motivation in middle-aged male mice. J Basic Clin Physiol Pharmacol. 2003, 14; 301-8.

9 Norhazlina Abdul Wahab et al. The effect of Eurycoma longifolia jack on spermatogenesis in estrogen-treated rats. Clinics. 2010, 65; 93-8.

10 Ang H H et al. Evaluation of the potency activity of aphrodisiac in Eurycoma longifolia Jack. Phytotherapy Research. 2001, 15; 435-436.

Kyowa Hakko USA

600 Third Ave., 19th Fl. New York, NY 10016 Phone: (800) 596-9252 Email: info@kyowa-usa.com Website: www.kyowa-usa.com

L-citrulline: A Powerful Ingredient for Health

L-citrulline is a non-essential amino acid that previously was thought of as just an intermediate metabolite. However, research over the past decade on L-citrulline has dramatically increased due to the understanding and importance of L-citrulline’s metabolism. L-citrulline is converted to L-arginine in the body, leading to increases in both L-arginine and nitric oxide (NO). Increased production of NO promotes vascular dilation, which helps support normal oxygen and blood circulation throughout the body.1 Since L-citrulline is not a component of proteins unlike most other amino acids, dietary proteins cannot be a direct source of L-citrulline to the body. As a result, interest in this nutrient is emerging in various applications for improving health and wellness. In this paper, we will specifically discuss L-citrulline’s role in NO production, vascular health, muscle protein synthesis, ammonia elimination and immune function.

NO Effects

As the natural precursor of L-arginine, L-citrulline plays an important role in the metabolism and regulation of NO, which is synthesized from L-arginine (as previously mentioned). An in-house study demonstrated that L-citrulline oral administration as compared to a control was able to effectively increase nitric oxide in SD rats.2

Ammonia Detoxification

L-citrulline is involved in ammonia detoxification as an L-ornithine cycle amino acid. L-citrulline, along with L-arginine and L-ornithine, has various functions as an amino acid in the L-ornithine cycle. The effect of supplemental L-citrulline on young animals fed arginine-deficient diets is similar to that of supplemental L-arginine. In rat experiments, L-citrulline was shown not only to promote the metabolism of ammonia accumulated in muscle during exercise, but also to elevate the survival rate of rats intraperitoneally injected with a lethal dose of ammonia.3

Effects on Muscle Protein Metabolism

A series of studies have proven that L-citrulline can increase muscle protein content and protein synthesis in animal models. Osowska et. al., found in malnourished aged rats that were fed a L-citrulline-supplemented diet, there was an increase in protein synthesis and protein content in the muscle as compared to the standard diet fed rats.4 It was also found that L-citrulline improved nitrogen balance in rats with short bowel syndrome. In addition, L-citrulline stimulates muscle protein synthesis in fasted adult rats.5 Most recently, Faure et. al., found that L-citrulline supplementation increases expression of the main myofibrillar proteins and seems to induce a switch in muscle energy metabolism, from aerobia toward anaerobia.6

Vascular Health

Because L-citrulline is an effective precursor of L-arginine for NO synthesis, it has been implicated to help support vascular health. More recently, many studies have been published exploring its use in various vascular disorders.7,8

Immune Function

L-citrulline may be a safe means of immunomodulation that preserves the anti-inflammatory mediator response.9

Safety Information

Because it occurs naturally in the living bodies of animals and humans where it plays an important role, L-citrulline is regarded as a highly safe ingredient. Studies in humans have demonstrated that L-citrulline is substantially innocuous.

Kyowa’s L-citrulline

Kyowa’s L-citrulline is an ultra-pure GRAS (generally recognized as safe) ingredient manufactured in the U.S. using a proprietary fermentation process.

References:

1 Bahri S. Zerrouk N. Aussel C. Citrulline: from metabolism to therapeutic use. Nutrition. 29(3):479-84, 2012.

2 Kyowa’s Hakko Bio, Ltd. In-house data.

3 Ortolani EL. Marcondes MC. Treatment of ammonia intoxication in rats through the use of amino acids from the urea cycle. Veterinary & Human Toxicology. 37(3):217-20, 1995.

4 Osowska S. Duchemann T. Walrand S. Paillard A. Citrulline modulates muscle protein metabolism in old malnourished rats. Am J Physiol Endocrinol Metab. 291: E582-E586, 2006.

5 Le Plenier S. Walrand S. Noirt R. Effects of Leucine and Citrulline versus non-essential amino acids on muscle protein synthesis in fasted rat: a common activation pathway? Amino Acids. 43(3): 1171-8, 2012.

6 Faure C. Morio B. Hartman WJ. Torre PM. Prior RL. Dietary citrulline but not ornithine counteracts dietary arginine deficiency in rats by increasing splanchnic release of citrulline. Journal of Nutrition. 124(10):1950-60, 1994.

7 Morita M. Sakurada M. Watanabe F. Effects of Oral L-citrulline Supplementation on Lipoprotein Oxidation and Endothelial Dysfunction in Humans with Vasospastic Angina. Immun., Endoc. & Metab. Agents in Med. Chem. 13: 1-7, 2013.

8 Ochiai M. Hayashi T. Morita M. Short-term effects of L-citrulline supplementation on arterial stiffness in middle-aged men. International Journal of Cardiology. 155:257-61, 2012.

9 Asgeirsson T., Zhang S., Nunoo R., Mascarenas C. Citrulline: A potential immunomodulator in sepsis. Surgery. 150: 744-51, 2011.

Nutegrity

1851 Kaiser Ave. Irvine, CA 92614 Phone: (949) 622-9030 • Fax: (949) 622-9033 Email: sales@nutegrity.com Website: www.nutegrity.com

SOLATHIN: Potato-Based Ingredient Offers Novel Weight Management Solution

As the obesity epidemic continues to be at the forefront of 21st century lifestyle concerns, medical professionals are searching for new ways to solve old problems. Despite the number of available solutions, obesity continues to rise, with estimates predicting that by 2030 more than half of Americans could be obese. The publication entitled “F as in Fat: How Obesity Threatens America’s Future”1 notes six million new cases of diabetes, five million cases of heart disease and stroke, and more than 400,000 cases of cancer in the next 20 years. On top of the medical concerns, projections show Americans could spend upward of $66 billion on treatment to fight illnesses associated with obesity and stand to lose more than $500 billion in economic productivity.

To add to the complexity of the issues at hand, weight management supplements have varied over time with most solutions also carrying a number of drawbacks. Traditionally, supplements have fallen into three broad categories: first, those that increase metabolism and energy expenditure; second, those that decrease appetite and hence decrease consumption of food; and finally, those that decrease the amount of food and calories absorbed by the body through the gastrointestinal (GI) tract. Solutions that increase metabolism have come under scrutiny for causing potentially damaging health effects as a result of increased heart rate, muscle work and reactive oxygen species (ROS). Supplements that promote decreased absorption of food have their own problems, creating unwanted side effects such as diarrhea and gas, and potentially causing serious harm by disrupting fluid balances in the body.

Recognizing the need for a safe and effective weight management solution, Nutegrity launched SOLATHIN®, a pure potato-protein extract that is derived from a mixture of natural potato proteins. The active component in SOLATHIN is a powerful appetite-suppressing agent known as Protease Inhibitor II, or PI-2, which has been studied for more than 20 years. Human clinical studies2-4 show that PI-2 significantly increases the level of cholecystokinin (CKK), a neuropeptide that acts to produce a feeling of fullness, thus helping to reduce food consumption.5-7 SOLATHIN differs from existing PI-2 products because it delivers a composition that is greater than 90 percent protein.

Clinically elevated CCK levels have been shown to directly reduce hunger and induce satiety by decreasing the rate of gastric emptying.8,9 Potatoes have high satiety properties thought to be a result of the presence of PI-2. Short-term study has demonstrated a decrease in total caloric intake by about 18 percent on average over a placebo.6 PI-2 consumption has also been shown to significantly increase plasma CCK level and delayed gastric emptying in addition to reducing postprandial levels of insulin and glucose.4

In a market with many options but few true solutions, SOLATHIN delivers compelling weight management supplementation. It presents a desirable solution that helps reduce food intake by increasing CCK levels to help promote feelings of fullness through PI-2 supplementation. SOLATHIN is hypo-allergenic and non-GMO (genetically modified organism), offering food manufacturers clean label claims, as well as texture and flavor enhancement.

References:

1 “F as in Fat: How Obesity Threatens America’s Future 2013.” Accessible at http://healthyamericans.org/report/108.

2 Peikin SR, Springer CJ, Dockray GJ, Calam J. Oral-administration of the protease inhibitor potato-2 stimulates release of cholecystokinin in man. Gastroenterology. 1987; 92: 1570.

3 Peikin SR. Role of cholecystokinin in the control of food intake. Gastroenterol Clin North America. 1989;18: 757–75.

4 Schwartz JG, Guan D, Green GM, Phillips WT. Treatment with an oral proteinase-inhibitor slows gastric- emptying and acutely reduces glucose and insulin levels after a liquid meal in type-ii diabetic-patients. Diab Care. 1994; 17: 255–262.

5 Liddle RA. Regulation of cholecystokinin secretion in humans. J Gastroenterol. 2000; 35: 181–87.

6 Hill AJ, Peikin SR, Ryan CA, Blundell JE. Oral-administration of proteinase inhibitor-ii from potatoes reduces energy-intake in man. Physiol Behav. 1990; 48: 241–46.

7 Vasselli JR, Greenfield D, Schwartz L, Heymsfield SB. Protease inhibitor from potatoes decreases hunger and increases fullness in overweight subjects following a meal. Obesity Res. 1989.

8 de Graaf C, Blom WA, Smeets PA, Stafleu A, Hendriks HF. Biomarkers of satiation and satiety. Am J Clin Nutr. 2004 Jun;79(6):946-61.

9 Little TJ, Horowitz M, Feinle-Bisset C. Role of cholecystokinin in appetite control and body weight regulation. Obesity Rev. 2005; 6: 297–306.

NutriScience Innovations, LLC

2450 Reservoir Ave. Trumbull, CT 06611 Phone: (203) 372-8877 • Fax: (203) 372-9977 Email: sales@nutriscienceusa.com Website: www.nutriscienceusa.com

Sugar Beet Extract: A Natural Betaine Source to Support the Body Inside & Out

Betaine is a naturally occurring nutrient found in most plants and animals; it serves as an osmolyte that protects against dehydration and stress associated with cell water loss. Natural sources of Betaine include shellfish, whole grains, spinach and beets. High-purity (≥98% by HPLC) supplemental Betaine Anhydrous can be obtained through the processing of sugar beets (Beta vulgaris) using a water extraction method. The high-purity Betaine Anhydrous present in natural sugar beet extract helps to protect cells against environmental stress, supports vital organs, improves physical performance and serves as a humectant to improve the health and feel of hair and skin. Natural Sugar Beet Extract is a multi-functional ingredient with offering numerous internal and external health benefits.

Betaine donates methyl groups (CH3) that support more than 100 normal cell functions. As a methyl donor, Betaine participates in the methionine cycle—primarily in the human liver and kidneys. Inadequate dietary intake of methyl groups leads to hypomethylation in many important pathways, including 1) disturbed hepatic protein (methionine) metabolism as determined by elevated plasma homocysteine concentrations and decreased S-adenosylmethionine concentrations, and 2) inadequate hepatic fat metabolism, which leads to steatosis (fatty accumulation).1 Betaine serves as a lipotrope, which prevents or reduces the accumulation of fat in the liver.

While engaging in athletic pursuits, the body is subject to physical stress and dehydration. When the body becomes fatigued and dehydrated, performance and stamina decrease. As an osmolyte, Natural Sugar Beet Extract plays a vital role in helping to protect against the negative impact of cell water loss. Consuming natural sugar beet extract may offer athletes a competitive edge by helping to improve overall athletic performance through increased power and strength. In a 2012 study on cycling sprint performance, it was found that daily consumption of 2.5 g of Betaine per day yielded increased average peak power, maximum peak power, average mean power and maximum mean power when compared to the baseline and placebo.2 Betaine was also observed to have a positive effect on body composition and performance in a 2013 study that also utilized a daily dose of 2.5 g of Betaine per day. It was observed that Betaine supplementation improved body composition, muscle size and work capacity.3

Water is essential to the health of our skin. Many external and environmental stressors can cause the skin to lose moisture and become dehydrated. Betaine has been shown to help soften skin by helping to establish better moisture balance. Additionally, Betaine offers protection against skin irritation, when used in conjunction with common detergents known to cause skin irritation.4,5 Betaine also has positive effect on hair and scalp health; hair care products containing betaine have been found to significantly improve the silky feel and final conditioning effect when compared to formulations without betaine.6

Consumption and use of Natural Betaine Anhydrous from sugar beet extract offers many positive health benefits from supporting important cell health functions vital to our organs to improving how our bodies perform during physical stress as well as improving conditions related to dehydration and cell water loss due to physical and environmental factors. Natural Betaine from Sugar Beet Extract is pH and heat stable up to 200 degrees C, allowing for easy formulation in a diverse range of applications including dietary supplements, functional foods and beverages, and personal care products.

NutriScience Innovations, LLC is provides research-based, innovative ingredients for the dietary supplement and functional food markets. It welcomes any questions regarding its Sugar Beet Extract (a natural source of Betaine Anhydrous), and encourages contact by phone at (203) 372-8877 or by visiting www.nutriscienceusa.com.

References:

1 Stuart, AS Craig. Betaine in human nutrition. Am J Clin Nutr. 2004, 80: 539-549.

2 Pryor, Luke J., et al. Effect of betaine supplementation on cycling sprint performance. J. Int. Soc. Sports Nutr. 2012, 9:12.

3 Cholew, Jason M., et al. Effects of betaine on body composition, performance, and homocysteine thiolactone. J. Int. Soc. Sports Nutr. 2013, 10:39.

4 Nicander, I., et al. The ability of betaine to reduce the irritating effects of detergents assessed visually, histologically and by bioengineering methods. Skin Res Technol. 2003, 9(1):50-58.

5 Nicander, I., et al. The use of different concentrations of betaine as a reducing irritation agent in soaps monitored visually and non-invasively. Skin Res Technol. 2003, 9(1):43-49.

6 Rigano, L., et al. Benefits of Trimethylglycine (Betaine) in Personal-Care Formulations. Cosmetics & Toiletries. 2000, 115(12): 47-54.

PLT Health Solutions, Inc.

119 Headquarters Plaza Morristown, NJ 07960 Phone: (973) 984-0900 • Fax:  (973) 984-5666 Email: plt@plthealth.com Website: www.plthealth.com

Synapsa Natural Memory Support: Peak Cognitive Performance for All Ages

An emerging trend in the cognitive health category is increasing interest by people in the 18 to 65 age group in achieving peak performance—whether in learning, memory or complex mental tasks. This should not come as a surprise considering the competitive nature of the global workplace and the increased mental demands of the information age. In the United States alone, there were nearly 22 million college and university students (U.S. Department of Education) in 2012. Studies show that there will be more than 100 million knowledge workers in the U.S. by the end of 2014 (Infotrends, 2011). Combined, these groups represent over 40 percent of the U.S. population. This indicates a vast need and market opportunity for the support of cognitive performance related to study and work.

Synapsa™ Natural Memory Support is a patented, standardized form of Bacopa monnieri that has been the subject of more than 30 years of research. Synapsa has been the focus of seven proof-of-concept clinical trials and seven double-blind, placebo-controlled, clinical studies. While much of the research that has been conducted in the cognitive health field has focused on the issue of cognitive decline—mainly in an aging population—most of the studies with Synapsa have focused on “peak cognitive performance” outcomes that offer benefits for a much broader population. These studies have shown support for two distinct types of benefit from Synapsa: daily, long-term (chronic) use to enhance learning and memory, and short-term (acute) use to improve mental performance in cognitively demanding situations, such as test taking. In the placebo-controlled clinical studies on Synapsa, healthy adults showed significantly improved performance in areas such as visual processing, learning rate, working memory, information retention and mental performance in cognitively demanding environments.

Studies Featuring Daily Use of Synapsa

The long-term or chronic use of Synapsa has been featured in four high-quality clinical trials since 2001. Three of these studies focused on the 18 to 65 age group.

• Visual Processing, Learning Rate & Memory Consolidation: A randomized, double-blind, placebo-controlled, 12-week study1 of 46 healthy adults, aged 18 to 60 years, showed a statistically significant improvement in speed of visual information processing, learning rate and memory consolidation in subjects. A statistically significant reduction in the rate of forgetting was also observed.

• Information Retention: A randomized, double-blind, placebo-controlled, 12-week trial2 on a group of 76 adults, aged 40 to 65 years, demonstrated a significant effect of Synapsa on the retention of new information.

• Working Memory, Visual Information Processing, Improved Accuracy: A randomized, double-blind, placebo-controlled, 90-day study3 with 62 participants, aged 18 to 60 years, showed a statistically significant improvement in working memory, visual information processing (sustained attention) and accuracy in complex cognitive tasks.

Acute Studies Featuring Synapsa

Two recent studies focused on short-term or acute results from using Synapsa. These studies examined mental performance in multitasking environments.

• Improved Performance on Demanding Cognitive Tests: Downey and colleagues4 (2012) examined efficacy of Synapsa in a study on sustained cognitive performance, evaluating the acute effect of Synapsa in healthy adult subjects. Significantly improved performance was seen in faster information processing and improved decision-making time, in a multitasking environment.

• Improved Performance in a Multitasking Environment: Benson and colleagues5 examined the impact of two different doses of Synapsa in a study with 17 healthy volunteers. Change from the baseline scores indicated positive cognitive effects, notably at both one-hour post- and two-hour post-Synapsa consumption on several measures of cognitive performance.

On-going Research Clinical studies on Synapsa Natural Memory support are on-going on a variety of fronts—to better understand the mechanism(s) of action and the impact of both long-term and short-term supplementation with the ingredient. In addition to work on the 18 to 65 age group, Synapsa has been chosen by the Australian Research Council for study in the Australian Research Council Longevity Intervention (ARCLI)—a study that is currently underway examining Synapsa supplementation in 465 cognitively healthy older adults (60-75 years old) over a 12-month period.6

References:

1 Stough C, et al. The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects. Psychopharmacology. 2001; 156(4):481-4.

2 Roodenrys S, Booth D, Bulzoni S, Phipps A, Micallef C, Smoker J. Chronic effects of Brahmi (Bacopa monnieri) on human memory. Neuropsychopharmacology. 2002; 27: 279–81.

3 Stough et al. Examining the nootropic effects of a special extract of Bacopa monniera on human cognitive functioning: 90-day double-blind placebo-contrlled randomized trial. Phytomedicine, 2008; 22:1629-34.

4 Downey, L.A., Murray, M., Rourke, J., Patak, B., Pase, M., Zangara, A., Scholey, A. & Stough, C. An acute, double-blind, placebo-controlled, crossover study of 320 mg and 640 mg doses of a special extract of Bacopa monnieri (CDRI 08) on sustained cognitive performance. Phytotherapy Research, 2012.

5 Benson, S., Downey, L.A., Stough, C., Wetherell, M., Zangara, A., & Scholey, A. An acute, double-blind, placebo-controlled, crossover study of 320 mg and 640 mg doses of Bacopa monnieri (CDRI 08) on multitasking stress reactivity and mood. Phythotherapy Research. 2013.

6 Stough, C., Pase, M., Cropley, V., Myers, S., Nolidin, K., King, R., Camfield, D., Wesnes, K., Pipingas, A., Croft, K., Chang, D. & Scholey, A. A randomized, controlled trial investigating the effect of Pycnogenol and Bacopa CDRI 08 herbal medicines on cognitive, cardiovascular, and biochemical functioning in cognitively healthy elderly people: the Australian Research Council Longevity Intervention (ARCLI) study protocol (ANZCTR12611000487910). Nutrition Journal. 2012; 11:1-9.

Sabinsa Corp.

20 Lake Dr. East Windsor, NJ 08520 Phone: (732) 777-1111 • Fax: (732) 777-1443 Email: info@sabinsa.com Website: www.sabinsa.com

The Brain Trust of Ingredients

The brain is the master regulatory organ that directly or indirectly controls the function of all the other organs and tissues in the body. Any dysfunctions in the brain eventually have an effect on other body functions. The human brain controls the central nervous system, the peripheral nervous system and regulates almost all human activity.1

The combination of high fat content and low antioxidant levels in the brain makes the brain vulnerable to fatty acid oxidation, called lipid peroxidation. Most degenerative diseases of the brain can be traced back to lipid peroxidation.2

Alzheimer’s disease is characterized by the presence of oxidized protein called amyloid beta peptide. There is a direct association between amyloid beta peptide formation and lipid peroxidation. Furthermore, amyloid beta peptide causes further damage to brain cells by causing further lipid peroxidation which produces more 4-hydroxynonenyl, a neurotoxic agent and which inhibits glucose uptake by brain cells.2

Brain Support Ingredients From Sabinsa

Sabinsa, a premier ingredients supplier inspired by ayurveda, has developed dietary supplements and nutraceuticals derived from plant sources using the latest technology. In the course of its research, it discovered several plant compounds that have various beneficial actions on brain health.

• Sabinsa’s Curcumin C3 Complex® (protected by U.S. Patent 5,861,415 & E.U. Patent 0839037) is obtained from turmeric and standardized for minimum 95 percent curcuminoids [curcumin, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC)].

• Testing anti-amyloid-beta phagocytosis in Alzheimer’s disease macrophages might be helpful for assessing the ability of patients to respond to immunomodulatory therapy with Curcumin C3 Complex.3

• Low plasma selenium status has been associated with senility and cognitive decline in the elderly and with Alzheimer’s disease. Selenium supplementation improves depressed mental states, mental fatigue and anxiety in adults.3,4 Sabinsa’s Selenium SeLECT® (L-Selenomethionine) and Methyselene® (L-Se-Methylselenocysteine, U.S. Patents 6,794,537 & 6,982,273) are two organic selenium complexes, more bioavailable compared to other inorganic selenium compounds.4,5

• Sabinsa’s Bacopin® is Bacopa monniera extract, a natural memory enhancing herb standardized for Bacosides. Bacosides promote nerve impulse transmission by repairing damaged neurons. This is done by enhancing kinase activity, neuronal synthesis and restoration of synaptic activity.6 Bacopa monniera inhibits lipid peroxidation and thereby prevents damage to cortical neurons.7

• Centella asiatica, branded as Centellin®, or gotu kola, is widely known in ayurvedic medicine. It boosts memory, has wound healing properties, and increases concentration, alertness, anti-anxiety and anti-stress. Centella improves short-term memory and learning performance due to its nootropic action involving cholinergic and GABAergic modulation. Centella also inhibits lipid peroxidation.8 Discover these and much more at www.sabinsa.com, or contact your Sabinsa sales representative today.

References:

1 Gray’s Anatomy for Students, October, 2004. Prof. Richard Drake, PhD, Churchill, Livingstone, publishers.

2 Mark RJ, Pang Z, Geddes JW, Uchida K, Mattson MP. Amyloid beta-peptide impairs glucose transport in hippocampal and cortical neurons: involvement of membrane lipid peroxidation. J Neurosci. 1997, Feb 1; 17(3):1046-54.

3 Laura Zhang, Milan Fiala, John Cashman, James Sayre, Araceli Espinosa, Michelle Mahanian, Justin Zaghi, Vladimir Badmaev, Michael C. Graves , George Bernard, and Mark Rosenthal. Curcuminoids enhance amyloid-β uptake by macrophages of Alzheimer’s disease patients. J. Alzheimers Dis. 2006; 10(1):1-7).

4 Benton D, Cook R, (1991) The impact of selenium supplementation on mood. Biol. Psychiatry. 29(11), 1092-8.

5 Gao et al. (2007) Selenium level and cognitive function in rural elderly Chinese. Am. J. Epidemiol. Apr. 15, 165(8), 955-65.

6 Stough C, Lloyd J, Clarke J, Downey LA, Hutchison CW, Rodgers T, Nathan PJ. The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects. Psychopharmacology (Berl). 2001, Aug; 156(4):481-4.

7 Limpeanchob N, Jaipan S, Rattanakaruna S, Phrompittayarat W, Ingkaninan K. Neuroprotecive effect of Bacopa monnieri on beta-amyloid-induced cell death in primary cortical culture. J Ethnopharmacol. 2008 Oct 30;120(1):112-7.

8 Tabassum R, Vaibhav K, Shrivastava P, Khan A, Ejaz Ahmed M, Javed H, Islam F, Ahmad S, Saeed Siddiqui M, Safhi MM, Islam F. Centella asiatica attenuates the neurobehavioral, neurochemical and histological changes in transient focal middle cerebral artery occlusion rats. Neurol Sci. 2013 Jun;34(6):925-33.

Stratum Nutrition/ESM Technologies

20 Research Park Dr. St. Charles, MO 63304 Phone: (888) 403-5039 Email: info@stratumnutrition.com Website: www.stratumnutrition.com

NEM: Exceptional Safety & Health Benefits for Joints and Surrounding Tissues

Whether the intent is to remain active or simply to stay mobile, maintaining joint health is important to all of us and increasingly so as we age. One ingredient that continues to gain appreciation for its combination of excellent joint health qualities is eggshell membrane, a unique ingredient derived from the thin inner membranes of chicken eggshells. This food-sourced ingredient is composed of matrix of proteins, including three different types of collagen, along with a variety of peptides and amino acids. In addition, it contains glucosamine, chondroitin sulfate, hyaluronic acid and other beneficial components associated with healthy joint tissues. NEM® is all-natural, patented and sustainably sourced from U.S.-domestic eggshells.

NEM is the only brand eggshell membrane supported by multiple published studies, which highlight its exceptional safety and health benefits for joints and surrounding tissues. Two open-label, pilot, clinical studies and one multicenter, randomized, double-blind, placebo-controlled, clinical study demonstrated NEM’s effectiveness in improving joint comfort and flexibility in people with osteoarthritis.1,2 The results from these studies were extended to a European population in an independent, multicenter, open-label, clinical trial recently conducted in Germany.3 These human studies were followed by an in-vitro human cell culture study revealing a potential mechanism of action.4 This study gave preliminary evidence that NEM exerts an immunomodulatory effect that inhibits the uncontrolled release of particular pro-inflammatory cytokines.

Adding to the expanding number of support studies, a newly published animal study further builds upon the in-vitro observations and provides more evidence for at least one of the ways in which NEM yields its positive effects.

The two primary mediators (cytokines) of joint inflammation are IL-1β and TNF-α. These cytokines can in turn induce chondrocytes (cartilage cells) to produce matrix metalloproteinases (MMPs), chemokines (IL-8, MCP-1, MIP-1α, MIP-1β, RANTES and others), as well as nitric oxide and prostaglandins, which subsequently leads to localized tissue destruction, immune cell infiltration, inhibition of cartilage matrix synthesis and increased pain sensitivity. The goal of the present study was to evaluate the effects of NEM on pro-inflammatory and anti-inflammatory cytokines following oral administration in both healthy and inflammation-induced rats.5

The results revealed a trend towards reduction of both IL-1β (Study 1) and TNF-α (Study 2) in healthy rats and statistically significant effects for nearly all of the chemokines (MCP-1, MIP-1α, MIP-1β, RANTES, VEGF) that are currently understood to play key roles in the inflammation and pathogenesis associated with both osteoarthritis and rheumatoid arthritis. It should also be appreciated that there was no negative effect from oral supplementation with NEM on anti-inflammatory cytokines and chemokines (IL-4, IL-6, IL-10 and TIMP-1) in the healthy rats.5

In inflammation-challenged rats (Study 3), there was a substantial (39 to 44 percent) and lasting (through 24 hours) reduction in IL-1β and a smaller but substantial (19 to 32 percent) decrease in TNF-α levels as well.5 These effects on the key mediators of joint inflammation provide further supportive evidence to the observed clinical efficacy of NEM. Evaluation of all of the results demonstrated that oral supplementation with NEM can influence both early-phase pro-inflammatory cytokines like IL-1β and TNF-α when inflammation is present. NEM can also influence later-phase pro-inflammatory cytokines like MCP-1, MIP-1α, MIP-1β, RANTES and VEGF under healthy non-inflammatory conditions. These results not only corroborate the results from the in-vitro mechanism of action study, but also point toward an exceptionally safe intervention for inflammatory conditions.

References:

1 Ruff KJ, DeVore DP, Leu MD, Robinson MA. Eggshell membrane: A possible new natural therapeutic for joint and connective tissue disorders. Results from two open-label human clinical studies. Clinical Interventions in Aging. 2009, 4:235-240.

2 Ruff KJ, Winkler A, Jackson RW, DeVore DP, Ritz BW. Eggshell Membrane in the Treatment of Pain and Stiffness from Osteoarthritis of the Knee: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Clinical Study. Clinical Rheumatology. 2009, 28:907-914.

3 Danesch U, Seybold M, Rittinghausen R, Treibel W, Bitterlich N. NEM Brand Eggshell Membrane Effective in the Treatment of Pain Associated with Knee and Hip Osteoarthritis: Results From A Six-center, Open-label German Clinical Study. Submitted for Publication.

4 Benson KF, Ruff KJ, Jensen GS. Effects of Natural Eggshell Membrane (NEM) on Cytokine Production in Cultures of Peripheral Blood Mononuclear Cells: Increased Suppression of Tumor Necrosis Factor-Levels After In-vitro Digestion. Journal of Medicinal Food. 2012, 15(4):360-368.

5 Ruff KJ. and DeVore DP: Reduction of pro-inflammatory cytokines in rats following 7-day oral supplementation with a proprietary eggshell membrane-derived product. Modern Research in Inflammation. 2014, 3:19-25.

U.S. Pharmacopeial Convention USP

12601 Twinbrook Pkwy. Rockville, MD 20852-1790 Phone: (301) 881-0666 • (800) 227-8772 Email: mediarelations@usp.org Website: www.usp.org

USP Focuses on Microbial Food Cultures

Live microbial food cultures (MFC) include cultures used for food fermentation or probiotic use. As a growing amount of MFC is used in food products, ways to ensure their integrity in food formulations are critical for manufacturers.

The Food Chemicals Codex (FCC)—a compendium of food ingredient standards developed by the U.S. Pharmacopeial Convention (USP)—has added an Appendix entitled, “Microbial Food Cultures Including Probiotics,” which provides food processors and manufacturers with guidance on the characterization of MFC. FCC standards help ensure the integrity of food ingredients by helping to determine their identity, quality and purity. These standards are published in the form of individual product monographs.

The Roles of MFC

MFC are often used in food production as a process aid (i.e. they are added for technological reasons but do not exhibit a function in the final product). For example, yeast is used in bakery products for fermentation, but is subsequently rendered inactive in the baking process. In these cases, they are often referred to as starter cultures or “preparations of microorganisms in their resting forms, whose metabolic activity has desired effects in the fermentation substrate food.”1 They are employed to transform historically uncontrolled fermentation processes performed by indigenous microorganisms into processes that are controlled with regard to predictability, reproducibility, economy, timing, safety and high standard of food quality.

However, in the case of the use of an MFC as a “probiotic” food ingredient, its role is rather functional. Generally speaking, the use of probiotics in foods is motivated by the health benefits purported to be conferred by a specific live microorganism. Because of genetic, biochemical and physiological differences among strains of the same species, care has to be taken to link the purported health benefits of probiotics to the specific strains (and intake levels) tested.2 In other words, health benefits cannot be transferred among different strains of the same species or genus without separate trials. In addition, there is a paucity of information on the role of a food matrix on probiotic physiology and function3, which are critical factors for the survivability of such microorganisms. With a growing trend toward the inclusion of probiotics in a diversity of foods, maintaining the viability of a probiotic ingredient in different food formulations and their concomitant storage conditions can be challenging, and it may be more difficult to understand if and how these different food products impact the physiological function of the probiotic in vivo.

Identity

Proper identification of a probiotic to the genus, species and strain level, however, is identified as a critical component in the FAO/WHO guidelines for use of probiotics in food4 and is needed to achieve correct packaging and labeling. Typically, DNA-based methods, as described in the FCC Appendix section called “Taxonomy—Identification,” are the most reliable for probiotic identification. It is becoming more common for whole genomic sequences to be known for commercial probiotic strains.5

USP’s First Probiotic Monograph

In December 2013, USP proposed a new standard for Bacillus coagulans GBI-30, 6086 in the FCC. This is the first proposed FCC monograph for a probiotic type of MFC. Bacillus coagulans GBI-30, 6086 is classified as a probiotic for its purported support to good digestive and immune health, and was the first Bacillus to receive GRAS (generally recognized as safe) notification from the U.S. Food and Drug Administration (FDA). The proposed monograph is specific to the strain level and represents only food ingredients that are labeled as this specific strain of Bacillus coagulans.

USP continues to seek sponsors of monographs for probiotics and other important food ingredients. For additional information about the FCC, visit http://uspgo.to/food-chemicals-codex.

References:

1 Vogel, R.F., W.P. Hammes, M. Habermeyer, K.H. Engel, Dr. Knoor and G. Eisenbrand. 2011. Microbial food cultures. Opinion of the Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFT). Molecular Nutrition & Food Research, 10.1002/mnfr.201100010, www.dfg.de/download/pdf/dfg_im_profil/reden_stellungnahmen/2-1-/sklm_microbial_food_cultures_100125_en.pdf.

2 Sanders, M. E. 2007. Probiotics: Strains Matter. Functional Food and Nutraceuticals. June: 34–41.

3 Sanders, M. E., and M. L. Marco. 2010. Food Formats for Effective Delivery of Probiotics. Annual Review of Food Science and Technology 1 (1:65–85) (04/01; 2011/02).

4 FAO. Guidelines for the Evaluation of Probiotics in Foods. In Food and Agriculture Organization of the United Nations (FAO) [database online]. London, Canada, 2002 [cited 5 March 2011]. Available from ftp://ftp.fao.org/es/esn/food/wgreport2.pdf.

5 Ventura, M., S. O’Flaherty, M. J. Claesson, F. Turroni, T. R. Klaenhammer, D. van Sinderen, and P. W. O’Toole. 2009. Genome-Scale Analyses of Health-Promoting Bacteria: Probiogenomics. Nat Rev Microbiol. 1 (7).

Verdure Sciences

1250 E. Conner St. Noblesville, IN 46060 Phone: (317) 776-3600 • Fax: (317) 776-3650 Email: info@vs-corp.com Website: www.vs-corp.com

Longvida Optimized Curcumin: A New Paradigm for Healthy Brain Aging

A new paradigm for healthy brain aging is emerging, involving three primary pathways: 1) oxidative stress and free radicals; 2) inflammatory modulation; and 3) regulation of lipid and protein aggregates in the brain. Longvida® Optimized Curcumin is supported by clinical data in all three pathways.

First, oxidative stress is a central factor contributing to brain aging. Curcumin’s antioxidant activity is generally considered to contribute to its diverse therapeutic effects for the brain and target organs.

Secondly, neuroinflammation is cited as a major issue for brain aging, presenting opportunities for nutritional interventions. Numerous research studies have found curcumin modulates inflammatory response by down-regulating activity of many inflammatory markers, including COX-2, TNF-a, NF-kB and cytokines.

The third pathway impacted by curcumin is accumulation of amyloid and tau protein in tissues such as the brain during the aging process. Data from a multi-center human trial in Australia and the U.S. shows Longvida curcumin can bind to amyloid plaques in brain tissue in less than one week.

A challenge in current use of traditional curcumin extracts is its limited bioavailability. When curcumin is consumed, it is converted to non-curcumin metabolites, such as curcumin glucuronide (often incorrectly marketed as curcumin). For example, several “enhanced” forms of curcumin, according to published academic studies, have led to no curcumin (free) in blood, only curcumin glucuronide.

Longvida Optimized Curcumin, based on patented Solid-Lipid Particle (SLP™) technology, was developed by Verdure in collaboration with University of California – Los Angeles (UCLA) neuroscientists Dr. Sally Frautschy, PhD, professor of medicine and neurology, and Dr. Gregory Cole, PhD, professor of medicine and neurology and associate director of the UCLA Alzheimer’s Disease Research Center. Longvida addresses the challenge of absorption of curcumin in its native, free form, reaching blood levels of free (unmetabolized) curcumin more than 65 times greater than non-optimized curcumin.

Based on extensive amounts of research showing efficacy in the brain in preclinical trials, Longvida has been the curcumin of choice in independent human trials at UCLA, Cedars-Sinai Medical Center in Los Angeles, Edith Cowan University, Emory University, the University of Colorado and The Ohio State University.

A randomized, double-blind, placebo-controlled, clinical study on 400 mg/day of Longvida by neuroscientists at Swinburne University in Melbourne, Australia, may be one of the first trials to demonstrate a nutritional supplement (Longvida, 80 mg curcumin) can improve acute and chronic cognitive function and mood in healthy older humans. Over 30 days, outcome measures included performance on key measures of the Computerized Mental Performance Assessment System (COMPASS) and validated measures of mood at acute (day one) and chronic (day 30) time points. Supplementation with Longvida led to significant improvements in working memory and attention tasks, and improved mental energy (fatigue), alertness, calmness and contentedness versus placebo. Excellent safety and tolerability was also reported.

Dr. Robert DiSilvestro, PhD from The Ohio State University Department of Human Nutrition, selected Longvida (80 mg curcumin) for a landmark study on aging-related biomarkers in healthy adults for its low dose, fast action and high bioavailability. His study showed significant improvements in biomarkers key for healthy brain aging, including an 11 percent reduction in plasma amyloid-beta. Curcumin is a key regulator of several steps in the oxidative stress and inflammatory cascade highly correlated with amyloid-beta and cognitive function. In subjects taking Longvida, a 72 percent increase in catalase and 11 percent reduction in C-reactive protein (CRP) were observed (p<0.05 from baseline). Blood lipids, vascular inflammation and oxidative stress are also highly correlated with healthy brain aging. After 30 days, significant 14 percent reduction in plasma triglycerides was observed coinciding with a trend for decrease of plasma cholesterol. Significant 14 percent reduction in vascular marker sICAM-1 and 37 percent increase in endothelial nitric oxide were also observed.

Together, clinical results indicate Longvida’s effectiveness supports a diverse array of biomarkers key for healthy aging of the brain and body.

Longvida is covered under Patent EP 1993365, additional patents pending. Longvida is a registered trademark of Verdure Sciences, Inc.

References:

Baum et al. Letter in J Clin Psychopharm. 2008:28(1), 110-114.

Baum et al. Pharmacol Res. 2007 Dec;56(6):509-14.

Cox and Scholey. Psychobiology, British Psychological Society Annual Meeting, 2013.

Cuomo et al. J Nat Prod. 2011 Mar 17.

DiSilvestro et al. Nutrition Journal. 2012, 11:79

Frautschy and Cole. Mol Neurobiol. 2010 Jun;41(2-3):392-409.

Gota et al. J Agric Food Chem. 2010 Feb 24;58(4):2095-9

Lao et al. BMC Complement Altern Med. 2006;6:10.

Marczylo et al. Cancer Chemother Pharmacol. 2007 Jul;60(2):171-7.

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