References

Current science supports the view that calcium is mainly absorbed in an ionized state in the small intestine through calcium channels in the enterocyte plasma membranes. Vitamin D3 stimulates the induction of calcium-binding proteins, enhancing calcium ion absorption via those channels.

An isotonic calcium preparation does not require lengthy dissolution in the stomach like a tablet, since the calcium and magnesium are largely in an ionized state. An isotonic product is sophisticated in its delivery system as compared to tablets or capsules. Note that the small intestine (and the very first part of the colon) can only absorb about 300-400 mg of calcium at a meal or from supplementation. The remainder is excreted in the feces.

References:

• Schaafsma, G., Bioavailabilty of Calcium and Magnesium, European Journal of Nutrition 1007;51:S13-16.
• Levenson, D.I., Bockman, R.S., A Review of Calcium Preparations, Nutrition Reviews 52: 221-232, 1994.
• Seigel, J.A. Biphasi nature of gastric emptying. Gut 29: 35-39, 1988
• Sladen, G.E. In: Transport across the Intestine. W.L. Burland and P.D. Samuel(eds.). New York: Academic Press., 1972.
• Graham, D.Y., J.L. Smith, and A.A. Bouvet. What happens to tablets in the stomach. Journal of Pharmaceutical Sciences 79(5): 420-424, 1990.
• Hunt, J.N. Properties of and alimentary osmoreceptor mechanism. Journal of Physiology (London) 132:267-288,1965.

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Free radicals, more accurately described as atoms or molecules with unpaired electrons, are highly reactive and readily undergo chemical reactions (1). Free radicals and their precursors can be produced endogenously through normal metabolic processes or exogenously through air pollutants, smoking and other sources. The body's natural defense mechanism to neutralize free radicals is the production and regeneration of antioxidants. When the concentration of free radicals exceeds the neutralizing capability of the body's antioxidants, these highly reactive species can damage vital molecules such as DNA, RNA, enzymes and structural proteins and large amounts of membrane lipids though peroxidation.

Vitamins and minerals are the most common forms of antioxidants within the body. Beta-Carotene, a member of the carotenoid family, supports normal functioning of the immune system and promotes ocular health (4,5). It promotes the normal development and differentiation of white blood cells that play a critical role in our immune system. Beta-Carotene is also metabolized into retinoic acid, a hormone that promotes normal embryonic development and the transcription of the gene for growth hormone (5). Vitamin C is a highly effective antioxidant, even in small amounts. It has been shown to protect critical molecules in the body such as lipids, proteins, and nucleic acids from free radicals and reactive oxygen species (1). Vitamin E is a fat-soluble antioxidant that protects vulnerable fatty acids in cell membranes from lipid peroxidation. It has also been shown to reduce the lipid oxidation of low-density lipoprotein (LDL) particles, thus promoting cardiovascular health (6). Other antioxidants such as vitamin C are involved in regenerating the antioxidant capability of vitamin E. Minerals are also key components of our immune system. Our body uses selenium-dependent enzymes known as selenoproteins to neutralize reactive oxygen species as well as reactive nitrogen species. Glutathione peroxidases are a group of selenoprotein enzymes that reduce reactive oxygen species such as hydrogen peroxide and lipid hydroperoxides to harmless products such as water and simple alcohols. Thioredoxin reductase is another selenium-dependent enzyme that participates in the regeneration of antioxidant systems, including vitamin C. Maintaining thioredoxin in its reduced form by thioredoxin reductase is important in supporting normal cell growth and vitality (7). Selenium deficiency has been strongly correlated with a weakened immune system (8).

Aside from the established health benefits of vitamins and minerals found in food, ancient medicine has introduced us to the world of herbal antioxidants. Green tea, a health-promoting antioxidant, is full of a powerful class of flavonoids known as catechins. Bilberry, a source of anthocyanidins has demonstrated health benefits ranging from cardiovascular health maintenance to support of cognitive brain function and vision (9). The powerful herb milk thistle has been widely used for almost 2000 years to support liver health (10). Medical doctor Kara Kelly and research scientist Janice Post-White state that preclinical evidence, both in vivo and in vitro, suggests that milk thistle promotes cellular health. (11). It is effective in promoting cell health by promoting normal levels of nuclear factor-kappa B (NF-κB). NF-κB is a transcription factor that activates cytokines, chemokines and leukocyte adhesion molecules involved in inflammatory responses. In an effort to reduce free radicals and promote optimal health, these vitamins, minerals and herbal antioxidants provide a safe, yet powerful supplement to our diet.*

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

References:

1. Flora, S. Role of free radicals and antioxidants in health and disease. Cellular and Molecular Biology. 53(1): 1-2, 2007.
2. Hwang, E. and Bowen, P. DNA damage, a biomarker of carcinogenesis: its measurement and modulation by diet and environment. Critical Reviews in Food Science and Nutrition. 47(1): 27-50, 2007.
3. Ozben, T. Oxidative stress and apoptosis: Impact on cancer therapy. Journal of Pharmaceutical Sciences. 96(9): 2181-2196, 2007.
4. Ross, A. Vitamin a supplementation and retinoic acid treatment in the regulation of antibody responses in vivo. Vitamins and Hormones. 75: 197-222, 2007.
5. Reichrath, J., et al. Vitamins as hormones. Hormone and Metabolic Research. 39(2): 71-84, 2007.
6. Munteanu, A., et al. Anti-atherosclerotic effects of vitamin E--myth or reality? Journal of Cellular and Molecular Medicine. 8(1): 59-76, 2004.
7. Holben, D. and Smith, A. The diverse role of selenium within selenoproteins: a review. Journal of the American Dietetic Association. 99(7): 836-843, 1999.
8. Brenneisen, P., et al. Selenium, oxidative stress, and health aspects. Molecular Aspects of Medicine. 26(4-5): 256-267, 2005.
9. Zafra-Stone, S., et al. Berry anthocyanins as novel antioxidants in human health and disease prevention. Molecular Nutrition and Food Research. 51(6): 675-683, 2007.
10. Tamayo, C. and Diamond, S. Review of clinical trials evaluating safety and efficacy of milk thistle (Silybum marianum [L.] Gaertn.). Integrative Cancer Therapies. 6(2): 146-157, 2007.
11. Post-White, J., et al. Advances in the use of milk thistle (Silybum marianum). Integrative Cancer Therapies. 6(2): 104-109, 2007.
12. Mayer, K., et al. Silymarin treatment of viral hepatitis: a systematic review. Journal of Viral Hepatitis. 12(6): 559-567, 2005.
13. Comelli, M., et al. Toward the definition of the mechanism of action of silymarin: activities related to cellular protection from toxic damage induced by chemotherapy. Integrative Cancer Therapies. 6(2): 120-129, 2007.

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Controlling joint inflammation generally targets the inhibition of prostaglandin production (via the COX enzyme) and leukotrienes (via the enzyme 5-LO). Many health professionals are not aware that there are safe, natural and effective nutritional and herbal approaches to promote bone and joint health. Some effective anti-inflammatory natural herbs include:

Boswellia serratea - (Frankincense)

• Indian plant - gummy resin found under the bark which contains active ingredients (boswellic acids).
• Blocks leukotriene biosynthesis by inhibiting 5-LO.
• May exhibit potent anti-inflammatory effects.
• Safety - not associated with gastro-intestinal side effects.

Scutellaria baicalensi - (Chinese Skullcap- Common Chinese herb used for centuries)

• Anti-Inflammatory properties
• Cyclo-oxygenase (COX-2) inhibition & 5- LO Inhibition
• Anti-oxidant

Oleanolic acid

• Found in numerous botanicals
• Animal models demonstrate:
• Cyclo-oxygenase (COX-2) inhibition
• Important to the maintenance of normal anti-inflammatory mechanisms
• Supports healthy GI tissues (gastroprotective)
• Promotes healthy liver function (hepatoprotective)

These natural anti-inflammatories are synergistic with glucosamine and do not carry side effects such as GI bleeding, interference with cartilage repair, acceleration of cartilage destruction or degradation of the bone matrix. Glucosamine is an amino-monosaccharide produced naturally in humans and needed for normal building and repairing cartilage.

References:

• Reginster JY, et al. Glucosamine sulfate significally reduces progression of knee osteoarthritis over 3 years: A large, randomized, placebo-controlled, double-blind, prospective trial. American College of Rheumatology Annual Meeting, Boston MA, 1999.
• Zerkak D, et al. The use of glucosamine therapy in osteoarthritis. Curr Rheumatol Rep 6:41-5, 2004.
• Matheson AJ, et al. Glucosamine: a review of its use in the management of osteoarthritis. Drugs Aging: 20:1041-60, 2003.
• Holick M, et al. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease and osteoporosis. Am J Clin Nutr 79: 362-71, 2004.
• Van Etten E, et al. 1,25-dihydroxycholecalciferol: endocrinology meets the immune system. Proc Nutrition Society 61:375-80, 2002.
• Bowman BA and Russell RM. Present Knowledge in Nutrition, International Life Sciences Institute, 2001.
• Hawk C. Manganese Deficiency and its Role in Structural Balance. The American Chiropractor, March/April, 1982.
• Ammon HP. Salai Guggal - Boswellia serrata: from a herbal medicine to a non-redox inhibitor of leukotriene biosynthesis. Eur J Med Res 1:369-70, 1996.
• Majeed, M. Boswellin: The Anti-inflammatory Phytonutrient. Piscataway, NJ: Nutriscience Publishers, Inc. 1996.
• Anonymous. Boswellia serrata. Alternative Medicine Review 3:306-7, 1998.
• Chi YS, et al. Effects of wogonin, a plant flavone from Scutellaria radix, on skin inflammation: in vivo regulation of inflammation-associated gene expression. Biochem Pharmacol. 2003 Oct 1;66(7): 127-8.
• Giner-Larza EM, et al. Oleanolic acid, a 3-oxotriterpene from Pistacia, inhibits leukotriene synthesis and has anti-inflammatory activity. Eur J Pharmacol 428: 137-43, 2001.
• Shimamura M, et al. Inhibition of angiogenesis by humulone, a bitter acid from beer hop. Biochem Biophys Res Commun 289:220-4, 2001.
• Lemay M, Murray MA, et al. In vitro and ex vivo cyclooxygenase inhibition by a hops extract. Asia Pacific J Clin Nutr 13 (Suppl): S110, 2004.
• Ricciardelli C, et al. Elevated stromal chondroitin sulfate glycosaminoglycan predicts progression in early-stage prostate cancer. Clin Cancer Res 3:983-92, 1997.

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OPCs are primarily derived from grape seed, pine bark and red wine. Each source has its own unique structure and exerts its own distinct biological activity, thus research scientists recommend an OPC product that contains a diverse blend of OPCs. Grape seed extract and pine bark extracts are exceptional sources of OPCs. These are the two most potent sources of OPCs. The third most abundant source of OPCs is red "wine" extract, as it is extracted from the OPC-rich skins and seeds of red grapes. Science shows OPCs' potential benefits include the following areas:

• Cholesterol: In vitro studies show OPCs neutralize reactive oxygen species (ROS), protecting against oxidation of LDL and promoting healthy cholesterol levels.
• Heart tissue: OPCs help maintain normal heart function.
• Vascular system: OPCs have been found to promote circulation, support healthy aortic tissue, plus improve capillary and microcapillary strength.
• Immune system: OPCs support healthy immune responses. In vitro, OPCs are shown to stimulate the secretion of gamma interferon – a cytokine that boosts immune responses.
• Blood Sugar Maintenance: OPCs from grape seed extract, in combination with niacin-bound chromium, have been found to combat free radical formation and promote healthy blood sugar maintenance.
• Brain tissue: In vitro studies show OPCs from pine bark and grape seed extracts offer protection against cellular damage, including DNA breakage within brain tissue (commonly found with exposure to free radicals and toxic agents).

References:

• J Med Food. 2003 Winter; 6(4):291-9.; Polyphenolics in grape seeds-biochemistry and functionality.; Shi J, Yu J, Pohorly JE, Kakuda Y.
• Curr Med Chem. 2004 May;11(10):1345-59.; Proanthocyanidins in health care: current and new trends.; Caos P, De Bruyne T, Hermans N, Apers S, Berghe DV, Vlietinck AJ.
• Altern Med Rev. 2003 Nov;8(4):442-50.Oligomeric proanthocyanidins (OPCs). Monograph.; [No authors listed]
• Biochem Pharmacol. 2003 Sep 15;66(6):947-54.; Antioxidant protection of low density lipoprotein by procyanidins: structure/activity relationships.; da Silva Porto PA, Laranjinha JA, de Freitas VA.
• New Phytol. 2005 Jan; 165(1):9-28; Proanthocyanidins -- a final frontier in flavonoid research? Dixon RA, Xie DY, Sharma SB.
• ISSN 1007-9327 CN 14-1219/R World J Gastroenterol 2005 August 14;11(30): 4674-4678 Anticancer effects of oligomeric proanthocyanidins on human colorectal cancer cell line, SNU-C4; Youn-Jung Kim, Hae-Jeong Park, Seo-Hyun Yoon, Mi-Ja Kim, Kang-Hyun Leem, Joo-Ho Chung, Hye-Kyung Kim H.
• J Agric Food Chem. 2004 Dec 29;52(26):7872-83.; Proteomics analysis of rat brain protein modulations by grapeseed extract.; Deshane J, Chaves L, Sarikonda KV, Isbell S, Wilson L, Kirk M, Grubbs C, Barnes S, Meleth S, Kim H.
• J Agric Food Chem. 2004 Oct 20; 52(21): 6433-42.Effective separation of potent antiproliferation and antiadhesion components from wild blueberry (Vaccinium angustifolium Ait.) fruits.
• Clin Sci (Lond). 2004 Nov; 107(5):513-7. The procyanidin-induced pseudo laminarshear stress response: a new concept for the reversal of endothelialdysfunction.; Corder R, Warburton RC, Khan NQ, Brown RE, Wood EG, Lees DM.;Schmidt BM, Howell AB, McEniry B, Knight CT, Seigler D, Erdman JW Jr, Lila MA.
• Res Vet Sci. 2004 Dec; 77(3): 239-43.; Green tea flavan-3-ols and oligomeric proanthocyanidins inhibit the motility of infective larvae of Teladorsagia circumcincta and Trichostrongylus colubriformis in vitro.; Molan AL, Sivakumaran S, Spencer PA, Meagher LP.
• Endocrinology. 2004 Nov; 145(11):4985-90. Epub 2004 Jul 22. Grapeseed-derived procyanidins have an antihyperglycemic effect in streptozotocin-induced diabeticrats and insulinomimetic activity in insulin-sensitive cell lines.; Pinent M, Blay M, Blade MC, Salvado MJ, Arola L, Ardevol A.
• Journal Angiology. 2008 Aug/Sept; 59(4):408-14.; Improvement in Circulation and in Cardiovascular Risk Factors With a Proprietary Isotonic Bioflavonoid Formula OPC-3.; Cesarone M, Di Renzo A, Errichi S, Schonlau F, Wilmer J, Blumenfeld J.

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Fish oils are derived predominantly from cold water fish which have fed on other marine life such as phytoplankton. These oils, rich in omega-3 fatty acids, are excellent sources of essential EPA and DHA. EPA and DHA have multiple actions in a number of body systems including the cardiovascular, ocular and the central nervous systems. In the cardiovascular system, fish oils have been shown to support healthy lipid parameters(1,2), blood pressure(3) and promote normal platelet activity(4,5). Studies by Calabresi(1) and Harris(2) have shown that as little as 1.5 grams of fish oils can support healthy cholesterol levels.

More recently, fish oils have been shown to have beneficial effects on vision health. Omega-3 fatty acid supplementation can help maintain visual acuity and support macular density as you age.* EPA and DHA supplementation have recently been investigated in new frontiers of neuroscience research. The brain's need for omega-3 fatty acids is now well established since about 20 percent of the brain by weight is composed of DHA(6).

The role of omega-3 fish oils for maintaining cognitive health during pregnancy is becoming increasingly clear and recognized. According to a news release of the American Psychiatric Association (May 2003), "During pregnancy, women who become depleted of omega-3 essential fatty acids have increased risk of depressive symptoms. With beneficial health effects and no adverse side effects, omega-3 fatty acids are shown to reduce the risk of depression in pregnancy," according to Dr Joseph Hibbeln, a psychiatrist and nationally recognized researcher from the National Institutes of Health.

Additionally, omega-3 fatty acid supplementation is becoming more main stream for clinicians in order to promote healthy cognitive function with stable mood(7).

References:

• Calabresi, L., et al. An omega-3 polyunsaturated fatty acid concentrate increases plasma high-density lipoprotein 2 cholesterol and paraoxonase levels in patients with familial combined hyperlipidemia. Metabolism. 53(2): 153-158, 2004.
• Marlene P. Freeman, Joseph R. Hibbeln, David Mischoulon, et al. Omega-3 Fatty Acids: Evidence for Treatment and Future Research in Psychiatry. Journal of Clinical Psychiatry, December 2006
• Harris, W. Fish oils and plasma lipid and lipoprotein metabolism in humans: a critical review. Journal of Lipid Research. 30(6): 785-807, 1989.
• Geleijnse, J., et al. Blood pressure response to fish oil supplementation: metaregression analysis of randomized trials. Journal of Hypertension. 20(8): 1493-1499, 2002.
• Mori, T., et al. Interactions between dietary fat, fish, and fish oils and their effects on platelet function in men at risk of cardiovascular disease. Atherosclerosis, Thrombosis, and Vascular Biology. 17(2): 279-286, 1997.
• Cangemi, F. TOZAL Study: an open case control study of an oral antioxidant and omega-3 supplement for dry AMD. BMC Ophthalmology. 7:3, 2007.
• Logan, A. Neurobehavioral aspects of omega-3 fatty acids: possible mechanisms and therapeutic value in major depression. Alternative Medicine Review. 8(4): 410-425, 2003.

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