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===Overview===
===Overview===
Twelve peer-reviewed research studies of Protandim have been published as of 2012; two<ref name=study1/><ref name=clinical2>{{cite journal|coauthors=Burnham EL, McCord JM, Bose S, Brown LA, House R, Moss M, Gaydos J|title=Protandim(R) does not influence alveolar epithelial permeability or intrapulmonary oxidative stress in human subjects with alcohol use disorders|journal=Am J Physiol Lung Cell Mol Physiol|year=2012|volume=Jan 20. [Epub ahead of print]|pmid=22268125|url=http://www.ncbi.nlm.nih.gov/pubmed/22268125}}</ref> were conducted in [[in vitro]] or [[in vivo]] animal models. Eleven additional studies have been done.<ref name=study1/><ref name=clinical2/><ref name=study2/><ref name=study3/><ref name=qurishi/><ref name=study9>{{cite journal | doi = 10.1016/j.mam.2011.10.006| author = Hybertson BM, Gao B, Bose SK, McCord JM| date = 2011 Oct 15. (Epub ahead of print)| title = Oxidative stress in health and disease: The therapeutic potential of Nrf2 activation | journal = Mol Aspects Med | volume = 32| issue = 4-6| pages = 234–46| url = | pmid = 22020111}}</ref><ref name=donovan/><ref name=study4/><ref name=Joddar/><ref name=Reuland/>
Twelve peer-reviewed research studies of Protandim have been published as of 2012; all but two<ref name=study1/><ref name=clinical2>{{cite journal|coauthors=Burnham EL, McCord JM, Bose S, Brown LA, House R, Moss M, Gaydos J|title=Protandim(R) does not influence alveolar epithelial permeability or intrapulmonary oxidative stress in human subjects with alcohol use disorders|journal=Am J Physiol Lung Cell Mol Physiol|year=2012|volume=Jan 20. [Epub ahead of print]|pmid=22268125|url=http://www.ncbi.nlm.nih.gov/pubmed/22268125}}</ref> were conducted in [[in vitro]] or [[in vivo]] animal models. Eleven of the studies were conducted, authored, and/or funded in whole or in part by LifeVantage and/or its employees, or by the company's predecessor, Lifeline Therapeutics.<ref name=study1/><ref name=clinical2/><ref name=study2/><ref name=study3/><ref name=qurishi/><ref name=study9>{{cite journal | doi = 10.1016/j.mam.2011.10.006| author = Hybertson BM, Gao B, Bose SK, McCord JM| date = 2011 Oct 15. (Epub ahead of print)| title = Oxidative stress in health and disease: The therapeutic potential of Nrf2 activation | journal = Mol Aspects Med | volume = 32| issue = 4-6| pages = 234–46| url = | pmid = 22020111}}</ref><ref name=donovan/><ref name=study4/><ref name=Joddar/><ref name=Reuland/>


Lifevantage advertises Protandim as a [[Nrf2]] activator.<ref>{{cite web |url=http://www.protandim.com/faq/ |title=FAQ |publisher=protandim.com}}</ref> A 2003 study showed that Nrf2 and [[heme oxygenase 1]] are induced by low doses of [[curcumin]], (a chemical constituent of [[turmeric]] and one of the principal ingredients in Protandim) in isolated [[kidney]] epithelial cells.<ref name= Balogun>{{cite journal | doi = 10.1042/BJ20021619| author = Balogun E, Hoque M, Gong P, Killeen E, Green CJ, Foresti R, Alam J, Motterlini R | year = 2003 | title = Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element| journal = Biochem J | volume = 371 | issue = 10 | pages = 887–95| pmid = 12570874 | pmc=1223348}}</ref>
Lifevantage advertises Protandim as a [[Nrf2]] activator.<ref>{{cite web |url=http://www.protandim.com/faq/ |title=FAQ |publisher=protandim.com}}</ref> A 2003 study showed that Nrf2 and [[heme oxygenase 1]] are induced by low doses of [[curcumin]], (a chemical constituent of [[turmeric]] and one of the principal ingredients in Protandim) in isolated [[kidney]] epithelial cells.<ref name= Balogun>{{cite journal | doi = 10.1042/BJ20021619| author = Balogun E, Hoque M, Gong P, Killeen E, Green CJ, Foresti R, Alam J, Motterlini R | year = 2003 | title = Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element| journal = Biochem J | volume = 371 | issue = 10 | pages = 887–95| pmid = 12570874 | pmc=1223348}}</ref>

A 2008 review article noted that while many supplements are claimed to act as antioxidants, changes in the levels of [[TBARS]] and increases in the levels of antioxidant enzymes in response to a treatment do not provide a reliable indication that the treatment has an antioxidant effect, since the same responses are produced by [[pro-oxidant]] compounds that induce oxidative stress. The authors suggested that measurement of [[isoprostane]]s might be a better indication of [[lipid peroxidation]] and oxidative damage to DNA.<ref>{{cite journal |last1=Knasmüller |first1=Siegfried |last2=Nersesyan |first2=Armen |last3=Mišík |first3=Miroslav |last4=Gerner |first4=Christopher |last5=Mikulits |first5=Wolfgang |last6=Ehrlich |first6=Veronika |last7=Hoelzl |first7=Christine |last8=Szakmary |first8=Akos |last9=Wagner |first9=Karl-Heinz |title=Use of conventional and -omics based methods for health claims of dietary antioxidants: a critical overview |journal=British Journal of Nutrition |volume=99 |pages=ES3–52 |year=2008 |pmid=18503734 |doi=10.1017/S0007114508965752}}</ref>

A 2011 blog by [[Harriet A. Hall]] in Science-Based Medicine stated, "We simply don’t know enough at this point to recommend Protandim for treatment or prevention of any disease, for anti-aging, for making people feel healthier or more energetic, or for anything else."<ref>{{cite web|last=Hall|first=Harriet|title=Pursued by Protandim Proselytizers|url=http://www.sciencebasedmedicine.org/index.php/pursued-by-protandim-proselytizers/|publisher=Science-Based Medicine|accessdate=12 November 2011}}</ref>


===Human clinical studies===
===Human clinical studies===
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===In vitro and animal studies===
===In vitro and animal studies===
In studies it was reported that Protandim increased glutathione levels in isolated cells<ref name=study2>{{cite journal |last1=Velmurugan |first1=K |last2=Alam |first2=J |last3=McCord |first3=J |last4=Pugazhenthi |first4=S |title=Synergistic induction of heme oxygenase-1 by the components of the antioxidant supplement Protandim |journal=Free Radical Biology and Medicine |volume=46 |issue=3 |pages=430–40 |year=2009 |pmid=19056485 |doi=10.1016/j.freeradbiomed.2008.10.050}}</ref> and that [[intraperitoneal]] injection of an alcohol-based extract of Protandim could suppress skin tumor incidence in an experimental model in mice<ref name=study3>{{cite journal |last1=Liu |first1=Jianfeng |last2=Gu |first2=Xin |last3=Robbins |first3=Delira |last4=Li |first4=Guohong |last5=Shi |first5=Runhua |last6=McCord |first6=Joe M. |last7=Zhao |first7=Yunfeng |title=Protandim, a Fundamentally New Antioxidant Approach in Chemoprevention Using Mouse Two-Stage Skin Carcinogenesis as a Model |journal=PLoS ONE |volume=4 |issue=4 |pages=e5284 |year=2009 |pmid=19384424 |pmc=2668769 |doi=10.1371/journal.pone.0005284}}</ref><ref name=robbins>{{cite journal | author = Robbins D, Zhao Y | date=23 March 2011| title = The role of manganese superoxide dismutase in skin cancer.
In studies published by LifeVantage executive [[Joe M. McCord|Joe McCord]] and colleagues, it was reported that Protandim increased glutathione levels in isolated cells<ref name=study2>{{cite journal |last1=Velmurugan |first1=K |last2=Alam |first2=J |last3=McCord |first3=J |last4=Pugazhenthi |first4=S |title=Synergistic induction of heme oxygenase-1 by the components of the antioxidant supplement Protandim |journal=Free Radical Biology and Medicine |volume=46 |issue=3 |pages=430–40 |year=2009 |pmid=19056485 |doi=10.1016/j.freeradbiomed.2008.10.050}}</ref> and that [[intraperitoneal]] injection of an alcohol-based extract of Protandim could suppress skin tumor incidence in an experimental model in mice<ref name=study3>{{cite journal |last1=Liu |first1=Jianfeng |last2=Gu |first2=Xin |last3=Robbins |first3=Delira |last4=Li |first4=Guohong |last5=Shi |first5=Runhua |last6=McCord |first6=Joe M. |last7=Zhao |first7=Yunfeng |title=Protandim, a Fundamentally New Antioxidant Approach in Chemoprevention Using Mouse Two-Stage Skin Carcinogenesis as a Model |journal=PLoS ONE |volume=4 |issue=4 |pages=e5284 |year=2009 |pmid=19384424 |pmc=2668769 |doi=10.1371/journal.pone.0005284}}</ref><ref name=robbins>{{cite journal | author = Robbins D, Zhao Y | date=23 March 2011| title = The role of manganese superoxide dismutase in skin cancer.
| journal = Enzyme Res| volume = Epub | issue = | pages = 409295| pmc=3092576 | pmid=21603266 | doi=10.4061/2011/409295}}</ref> and result in suppression of [[p53]] and induction of [[SOD2|MnSOD]] in isolated mouse epidermal cells in vitro.<ref name=robbins>{{cite journal |last1=Robbins |first1=Delira |last2=Gu |first2=Xin |last3=Shi |first3=Runhua |last4=Liu |first4=Jianfeng |last5=Wang |first5=Fei |last6=Ponville |first6=Jacqulyne |last7=McCord |first7=Joe M. |last8=Zhao |first8=Yunfeng |title=The Chemopreventive Effects of Protandim: Modulation of p53 Mitochondrial Translocation and Apoptosis during Skin Carcinogenesis |journal=PLoS ONE |volume=5 |issue=7 |pages=e11902 |year=2010 |pmid=20689586 |pmc=2912769 |doi=10.1371/journal.pone.0011902}}</ref>
| journal = Enzyme Res| volume = Epub | issue = | pages = 409295| pmc=3092576 | pmid=21603266 | doi=10.4061/2011/409295}}</ref> and result in suppression of [[p53]] and induction of [[SOD2|MnSOD]] in isolated mouse epidermal cells in vitro.<ref name=robbins>{{cite journal |last1=Robbins |first1=Delira |last2=Gu |first2=Xin |last3=Shi |first3=Runhua |last4=Liu |first4=Jianfeng |last5=Wang |first5=Fei |last6=Ponville |first6=Jacqulyne |last7=McCord |first7=Joe M. |last8=Zhao |first8=Yunfeng |title=The Chemopreventive Effects of Protandim: Modulation of p53 Mitochondrial Translocation and Apoptosis during Skin Carcinogenesis |journal=PLoS ONE |volume=5 |issue=7 |pages=e11902 |year=2010 |pmid=20689586 |pmc=2912769 |doi=10.1371/journal.pone.0011902}}</ref>


An in vitro gene expression microarray study in 2011 examined the effect of Protandim on gene expression profiles in human primary vascular [[Endothelium|endothelial cells]] and a SK-N-MC human neuroblastoma-derived cell line. Protandim was found to upregulate Nrf-2 and to modulate the expression of a variety of other genes.<ref>http://www.sciencedirect.com/science/article/pii/S0098299711000501</ref> Similarly, an alcohol-based extract of Protandim was found to induce Nrf2 nuclear localization, phase II antioxidant enzyme expression, and Nrf2-dependent protection from [[hydrogen peroxide]]-mediated oxidative stress stress in isolated human coronary artery endothelial cells<ref name=donovan>{{cite journal | author = Donovan EL, McCord JM, Reuland DJ, Miller BF, Hamilton KL | year=2012| title = Phytochemical activation of Nrf2 protects human coronary artery endothelial cells against an oxidative challenge | journal = Oxid Med Cell Longev | volume = 2012| issue = | pages = Article ID 132931| url = http://www.hindawi.com/journals/oximed/2012/132931/| pmc= | pmid= 22685617| doi=10.1155/2012/132931}}</ref> and mouse cardiomyocytes in vitro.<ref name= Reuland>{{cite journal | author = Reuland DJ, Khademi S, Castle CJ, Irwin DC, McCord JM, Miller BF, Hamilton KL. | year = 2012| title = Upregulation of phase II enzymes through phytochemical activation of Nrf2 protects cardiomyocytes against oxidant stress | journal =Free Radical Biology and Medicine|volume = | issue = | pages = | url = http://www.sciencedirect.com/science/article/pii/S0891584912018254}}</ref>
An in vitro gene expression microarray study published by Dr. McCord and associates in 2011 examined the effect of Protandim on gene expression profiles in human primary vascular [[Endothelium|endothelial cells]] and a SK-N-MC human neuroblastoma-derived cell line. Protandim was found to upregulate Nrf-2 and to modulate the expression of a variety of other genes.<ref>http://www.sciencedirect.com/science/article/pii/S0098299711000501</ref> Similarly, an alcohol-based extract of Protandim was found to induce Nrf2 nuclear localization, phase II antioxidant enzyme expression, and Nrf2-dependent protection from [[hydrogen peroxide]]-mediated oxidative stress stress in isolated human coronary artery endothelial cells<ref name=donovan>{{cite journal | author = Donovan EL, McCord JM, Reuland DJ, Miller BF, Hamilton KL | year=2012| title = Phytochemical activation of Nrf2 protects human coronary artery endothelial cells against an oxidative challenge | journal = Oxid Med Cell Longev | volume = 2012| issue = | pages = Article ID 132931| url = http://www.hindawi.com/journals/oximed/2012/132931/| pmc= | pmid= 22685617| doi=10.1155/2012/132931}}</ref> and mouse cardiomyocytes in vitro.<ref name= Reuland>{{cite journal | author = Reuland DJ, Khademi S, Castle CJ, Irwin DC, McCord JM, Miller BF, Hamilton KL. | year = 2012| title = Upregulation of phase II enzymes through phytochemical activation of Nrf2 protects cardiomyocytes against oxidant stress | journal =Free Radical Biology and Medicine|volume = | issue = | pages = | url = http://www.sciencedirect.com/science/article/pii/S0891584912018254}}</ref>


Another study investigated the effect of intraperitoneal injection of an alcohol-based extract of Protandim
Another study conducted by Dr. McCord and associates investigated the effect of intraperitoneal injection of an alcohol-based extract of Protandim
in an experimental model of [[pulmonary hypertension]] in rats. It was reported that the extract induced myocardial nuclear factor E2-related factor 2 and heme oxygenase 1, prevented a loss of myocardial capillaries, minimized fibrosis and preserved RV function
in an experimental model of [[pulmonary hypertension]] in rats. It was reported that the extract induced myocardial nuclear factor E2-related factor 2 and heme oxygenase 1, prevented a loss of myocardial capillaries, minimized fibrosis and preserved RV function
<ref name=study4>{{cite journal |last1=Bogaard |first1=H. J. |last2=Natarajan |first2=R. |last3=Henderson |first3=S. C. |last4=Long |first4=C. S. |last5=Kraskauskas |first5=D. |last6=Smithson |first6=L. |last7=Ockaili |first7=R. |last8=McCord |first8=J. M. |last9=Voelkel |first9=N. F. |title=Chronic Pulmonary Artery Pressure Elevation Is Insufficient to Explain Right Heart Failure |journal=Circulation |volume=120 |issue=20 |pages=1951–1960 |year=2009 |pmid=19884466 | doi=10.1161/CIRCULATIONAHA.109.883843}}</ref>
<ref name=study4>{{cite journal |last1=Bogaard |first1=H. J. |last2=Natarajan |first2=R. |last3=Henderson |first3=S. C. |last4=Long |first4=C. S. |last5=Kraskauskas |first5=D. |last6=Smithson |first6=L. |last7=Ockaili |first7=R. |last8=McCord |first8=J. M. |last9=Voelkel |first9=N. F. |title=Chronic Pulmonary Artery Pressure Elevation Is Insufficient to Explain Right Heart Failure |journal=Circulation |volume=120 |issue=20 |pages=1951–1960 |year=2009 |pmid=19884466 | doi=10.1161/CIRCULATIONAHA.109.883843}}</ref>


Other studies have examined the effects of Protandim on fibrosis in a rodent model of [[Duchenne muscular dystrophy|Duchenne muscular dystrophy (DMD)]]<ref name=qurishi>{{cite journal |last1=Qureshi |first1=Muhammad Muddasir |last2=McClure |first2=Warren C. |last3=Arevalo |first3=Nicole L. |last4=Rabon |first4=Rick E. |last5=Mohr |first5=Benjamin |last6=Bose |first6=Swapan K. |last7=McCord |first7=Joe M. |last8=Tseng |first8=Brian S. |title=The Dietary Supplement Protandim® Decreases Plasma Osteopontin and Improves Markers of Oxidative Stress in Muscular DystrophyMdxMice |journal=Journal of Dietary Supplements |volume=7 |issue=2 |pages=159–178 |year=2010 |pmid=20740052 |pmc=2926985 |doi=10.3109/19390211.2010.482041}}</ref> and the effects of an alcohol extract of Protandim in an [[in vitro]] saphenous vein graft model.<ref name=Joddar>{{cite journal |last1=Joddar |first1=Binata |last2=Reen |first2=Rashmeet K. |last3=Firstenberg |first3=Michael S. |last4=Varadharaj |first4=Saradhadevi |last5=McCord |first5=Joe M. |last6=Zweier |first6=Jay L. |last7=Gooch |first7=Keith J. |title=Protandim attenuates intimal hyperplasia in human saphenous veins cultured ex vivo via a catalase-dependent pathway |journal=Free Radical Biology and Medicine |volume=50 |issue=6 |pages=700–9 |year=2011 |pmid=21167278 |doi=10.1016/j.freeradbiomed.2010.12.008}}</ref> In a study investigating the effects of various agents on skeletal muscle tissue function in an in vitro model of DMD, compounds used clinically for DMD treatment, such as the [[glucocorticoids]], were found to produce a potentially beneficial increase in muscular contractile force, while Protandim produced the opposite effect, significantly inhibiting contractile force.<ref name= Vandenburgh>{{cite journal | doi = 10.1096/fj.09-134411| author = Vandenburgh H, Shansky J, Benesch-Lee F, Skelly K, Spinazzola JM, Saponjian Y, Tseng BS | year = 2009 | title = Automated drug screening with contractile muscle tissue engineered from dystrophic myoblasts| journal = FASEB J | volume = 23 | issue = 10 | pages = 3325–34| url = http://www.fasebj.org/content/23/10/3325.long| pmid = 19487307}}</ref>
Other studies by McCord and colleagues have examined the effects of Protandim on fibrosis in a rodent model of [[Duchenne muscular dystrophy|Duchenne muscular dystrophy (DMD)]]<ref name=qurishi>{{cite journal |last1=Qureshi |first1=Muhammad Muddasir |last2=McClure |first2=Warren C. |last3=Arevalo |first3=Nicole L. |last4=Rabon |first4=Rick E. |last5=Mohr |first5=Benjamin |last6=Bose |first6=Swapan K. |last7=McCord |first7=Joe M. |last8=Tseng |first8=Brian S. |title=The Dietary Supplement Protandim® Decreases Plasma Osteopontin and Improves Markers of Oxidative Stress in Muscular DystrophyMdxMice |journal=Journal of Dietary Supplements |volume=7 |issue=2 |pages=159–178 |year=2010 |pmid=20740052 |pmc=2926985 |doi=10.3109/19390211.2010.482041}}</ref> and the effects of an alcohol extract of Protandim in an [[in vitro]] saphenous vein graft model.<ref name=Joddar>{{cite journal |last1=Joddar |first1=Binata |last2=Reen |first2=Rashmeet K. |last3=Firstenberg |first3=Michael S. |last4=Varadharaj |first4=Saradhadevi |last5=McCord |first5=Joe M. |last6=Zweier |first6=Jay L. |last7=Gooch |first7=Keith J. |title=Protandim attenuates intimal hyperplasia in human saphenous veins cultured ex vivo via a catalase-dependent pathway |journal=Free Radical Biology and Medicine |volume=50 |issue=6 |pages=700–9 |year=2011 |pmid=21167278 |doi=10.1016/j.freeradbiomed.2010.12.008}}</ref> In a study investigating the effects of various agents on skeletal muscle tissue function in an in vitro model of DMD, compounds used clinically for DMD treatment, such as the [[glucocorticoids]], were found to produce a potentially beneficial increase in muscular contractile force, while Protandim produced the opposite effect, significantly inhibiting contractile force.<ref name= Vandenburgh>{{cite journal | doi = 10.1096/fj.09-134411| author = Vandenburgh H, Shansky J, Benesch-Lee F, Skelly K, Spinazzola JM, Saponjian Y, Tseng BS | year = 2009 | title = Automated drug screening with contractile muscle tissue engineered from dystrophic myoblasts| journal = FASEB J | volume = 23 | issue = 10 | pages = 3325–34| url = http://www.fasebj.org/content/23/10/3325.long| pmid = 19487307}}</ref>


==Legal issues==
==Legal issues==

Revision as of 01:23, 13 January 2013

LifeVantage
Company typePublic
Nasdaq: LFVN
IndustryNutrition, Skin Care products
Founded2003
Headquarters
Salt Lake City, Utah
,
United States
Area served
United States, Canada, Japan, Mexico, Australia, Hong Kong
Key people
Douglas C. Robinson, David W. Brown, Kirby Zenger, David Colbert, Darlene R. Walley, Joe M. McCord
ProductsProtandim, TrueScience
RevenueIncrease US$ 126.2 million [1]
US$ 17 million[1]
WebsiteLifeVantage.com

Protandim is a patented[2] dietary supplement marketed by LifeVantage Corporation (Nasdaq: LFVN; formerly LifeLine Therapeutics and Yaak River Resources, Inc), a Utah-based multilevel marketing company.[3] The manufacturers of Protandim claim the product can indirectly increase antioxidant activity by upregulating endogenous antioxidant factors such as the enzymes superoxide dismutase (SOD) and catalase, as well as the tripeptide glutathione. Like all dietary supplements, Protandim has not been evaluated by the U.S. Food and Drug Administration (FDA) and "is not intended to diagnose, treat, cure, or prevent any disease."[4]

Product History

In 2003, Lifeline Therapeutics, a privately held Denver-based nutraceutical licensing and marketing company, entered into a joint agreement with Massachusetts biotechnology company CereMedix for the rights to market CMX-1152, an experimental peptide-based compound, under the brand name "Protandim" (also sometimes referred to at that time as "Rholen," "Rejuven8r" and "ependymin").[5][6][7][8][9][10][11] CereMedix was a ten percent owner of Lifeline and members of the CereMedix management board served on Lifeline’s board of directors. CMX-1152 was claimed to upregulate the production of the endogenous antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase and offset the ageing process, potentially allowing people to live up to the age of 120.[10]

CMX-1152 was due to be marketed as an over the counter anti-aging pill in June 2004 after completing human clinical trials. However, plans to market the CMX-152 version of Protandim fell through and in April 2004 Lifeline Therapeutics announced that it would instead be marketing a different (non-peptide) dietary supplement under the name “Protandim CF” (to distinguish it from the peptide version initially developed by Cermedix). The new version of Protandim, a combination of 5 common herbal ingredients including turmeric and green tea was invented following “months of extensive research and development” by Lifeline employees Paul Myhill and William Driscoll (a former oil company executive), who together hold the patent on the product,[2] and it was officially launched in February 2005. Myhill and Driscoll resigned from the company later that year.[11][12][13][14]

Like CMX-1152, the herbal version of Protandim that supplanted it was marketed by Lifeline as an "anti-aging" supplement that increases the body’s antioxidant defenses by upregulating superoxide dismutase, catalase, and glutathione peroxidase. According to the company, the product was initially sold through retail channels such as GNC;[15] however, in 2009, after several consecutive years of multimillion dollar losses, the company, which by then was doing business under the name LifeVantage, stopped marketing Protandim through retailers and switched to multilevel marketing, selling it instead through a network of commissioned independent distributors exclusively. According to LifeVantage, the move from retail to multi-level marketing was prompted by the January 2008 hiring of David W. Brown, (formerly CEO and president of Metabolife) as the company's CEO and president.[16][17]

Beginning in 2005, Protandim was produced under a manufacturing agreement with The Chemins Company of Colorado Springs, Colorado.[18] In July 2008, LifeVantage entered into a new manufacturing agreement with Cornerstone Research & Development to produce Protandim, and with Wasatch Product Development to produce a Protandim-based skin cream (TrueScience).[19]

In December 2012, LifeVantage issued a voluntary recall of select lots of Protandim due to potential health risks arising from the possible inclusion of small metal fragments in the final product.[20]

Composition

Protandim consists mainly of a blend of 5 herbal ingredients (amounts per caplet listed in parentheses):

Additional ingredients include: calcium, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, modified cellulose, silica, and stearic acid.[citation needed]

Side effects

The side effects of Protandim may include allergic responses, gastrointestinal disturbances (stomach ache, diarrhea, vomiting), headache, and rash of the hands and feet.[21][third-party source needed]

Research

Overview

Twelve peer-reviewed research studies of Protandim have been published as of 2012; all but two[22][23] were conducted in in vitro or in vivo animal models. Eleven of the studies were conducted, authored, and/or funded in whole or in part by LifeVantage and/or its employees, or by the company's predecessor, Lifeline Therapeutics.[22][23][24][25][26][27][28][29][30][31]

Lifevantage advertises Protandim as a Nrf2 activator.[32] A 2003 study showed that Nrf2 and heme oxygenase 1 are induced by low doses of curcumin, (a chemical constituent of turmeric and one of the principal ingredients in Protandim) in isolated kidney epithelial cells.[33]

A 2008 review article noted that while many supplements are claimed to act as antioxidants, changes in the levels of TBARS and increases in the levels of antioxidant enzymes in response to a treatment do not provide a reliable indication that the treatment has an antioxidant effect, since the same responses are produced by pro-oxidant compounds that induce oxidative stress. The authors suggested that measurement of isoprostanes might be a better indication of lipid peroxidation and oxidative damage to DNA.[34]

A 2011 blog by Harriet A. Hall in Science-Based Medicine stated, "We simply don’t know enough at this point to recommend Protandim for treatment or prevention of any disease, for anti-aging, for making people feel healthier or more energetic, or for anything else."[35]

Human clinical studies

Two studies of Protandim have been conducted in human subjects. One of these studies, a non-randomized, non-controlled trial, reported that Protandim increased the levels of the antioxidant enzymes SOD and catalase red blood cells while reducing TBAR levels in blood plasma.[7][22]

The second study, a double-blinded, randomized, placebo-controlled trial published by McCord and colleagues in 2012, examined the effect of Protandim on pulmonary oxidative stress and alveolar epithelial permeability in 30 recovering alcoholics.[23] Protandim (14 subjects at a dose of 1350 mg/day; double the daily dose recommended by the manufacturer) or placebo (in 16 subjects) were administered for 7 days. Relative to placebo-treatment, Protandim had no significant effects on alveolar epithelial permeability or on oxidative stress, epithelial growth factor, fibroblast growth factor, interleukin-1β, and interleukin-10 levels in bronchoalveolar lavage fluid. Treatment with placebo, however, produced a significant reduction in plasma levels of TBARS, a marker of oxidative stress (i.e., lipid peroxidation).

In vitro and animal studies

In studies published by LifeVantage executive Joe McCord and colleagues, it was reported that Protandim increased glutathione levels in isolated cells[24] and that intraperitoneal injection of an alcohol-based extract of Protandim could suppress skin tumor incidence in an experimental model in mice[25][36] and result in suppression of p53 and induction of MnSOD in isolated mouse epidermal cells in vitro.[36]

An in vitro gene expression microarray study published by Dr. McCord and associates in 2011 examined the effect of Protandim on gene expression profiles in human primary vascular endothelial cells and a SK-N-MC human neuroblastoma-derived cell line. Protandim was found to upregulate Nrf-2 and to modulate the expression of a variety of other genes.[37] Similarly, an alcohol-based extract of Protandim was found to induce Nrf2 nuclear localization, phase II antioxidant enzyme expression, and Nrf2-dependent protection from hydrogen peroxide-mediated oxidative stress stress in isolated human coronary artery endothelial cells[28] and mouse cardiomyocytes in vitro.[31]

Another study conducted by Dr. McCord and associates investigated the effect of intraperitoneal injection of an alcohol-based extract of Protandim in an experimental model of pulmonary hypertension in rats. It was reported that the extract induced myocardial nuclear factor E2-related factor 2 and heme oxygenase 1, prevented a loss of myocardial capillaries, minimized fibrosis and preserved RV function [29]

Other studies by McCord and colleagues have examined the effects of Protandim on fibrosis in a rodent model of Duchenne muscular dystrophy (DMD)[26] and the effects of an alcohol extract of Protandim in an in vitro saphenous vein graft model.[30] In a study investigating the effects of various agents on skeletal muscle tissue function in an in vitro model of DMD, compounds used clinically for DMD treatment, such as the glucocorticoids, were found to produce a potentially beneficial increase in muscular contractile force, while Protandim produced the opposite effect, significantly inhibiting contractile force.[38]

In 2009, LifeVantage was sued by Utah-based Zrii LLC, a marketer of nutritional fruit drinks endorsed by Deepak Chopra, based on allegations that LifeVantage had conspired with former Zrii executives to “ruin the company” and take it over “on the cheap” following a “mass exodus”. The case was closed in December 2009 following LifeVantage’s settlement payment of $400,000 to Zrii.[39]

On October 14, 2011, Burke Hedges, a former high-level LifeVantage distributor, filed a lawsuit with the Utah District Court against LifeVantage and its executives, seeking $3 million in punitive damages over allegations of wrongful termination and tortious interference.[40]

Advertising and sponsorship

LifeVantage commissioned a Denver-based public relations firm to secure product placement for Protandim on various radio and TV programs including two segments of the television program Today.[41] One of the segments featured nutritionist Elizabeth Somer, who was hired as a consultant/spokesperson for Protandim.[42][43]

On June 20, 2007, LifeVantage announced that it had entered into a 3-year agreement with TV personality Montel Williams to act as a spokesperson for the company’s products.[44] On September 15, 2011, LifeVantage entered into a similar 2-year agreement with entertainer Donny Osmond, stipulating that the company would pay Osmond for various promotional appearances and video recordings and commissions for sales of LifeVantage products.[45]

Product development

As recently as July 21, 2011, LifeVantage credited McCord as the creator of Protandim on its website.[46] At a 2011 conference for LifeVantage distributors, McCord stated, "I was presented with a list of 41 potential ingredients for a product they wanted to call Protandim, and I went through the list and penciled out, rapidly, about 36 of those ingredients," leaving the 5 ingredients in the current formulation of Protandim.[47] In March 2009, former LiveVantage executive, Paul Myhill stated, "We initially decided to hide that fact [that Myhill derived the formulation for Protandim] for marketing purposes and instead rely on the impeccable background of Dr. McCord." [48] In April, 2005, Myhill produced a signed letter from McCord in which McCord stated, "I do not honestly feel that I have made contributions to the intellectual property, up to this point, that would qualify me as an inventor... I must congratulate you and Paul for having framed the concept of Protandim so close to its final embodiment, prior to the beginnings of our association."[49]

References

  1. ^ a b http://biz.yahoo.com/e/120910/lfvn10-k.html
  2. ^ a b US 7241461, Myhill, Paul R. & Driscoll, William J., "Composition for alleviating inflammation and oxidative stress in a mammal.", issued 10 July 2007 
  3. ^ LifeVantage Corporation"www.lifevantage.com". Retrieved 29 March 2010.
  4. ^ This statement or disclaimer is required by US law (DSHEA) when a manufacturer makes a structure/function claim on a dietary supplement label within the United States of America. "FDA: Overview of Dietary Supplements". Retrieved 25 March 2010.
  5. ^ "Lifeline Nutraceuticals, CereMedix sign agreement". Nutraceuticals World. December 1, 2003. Retrieved 08/19/2012. {{cite news}}: Check date values in: |accessdate= (help)
  6. ^ "The Uncertain Antiaging Pill (press release)". Betterhumans. December 1, 2004. Retrieved 08/19/2012. {{cite news}}: Check date values in: |accessdate= (help)
  7. ^ a b Alison McCook (2006). "Your Money for Your Life". The Scientist. 20 (3): 33. {{cite journal}}: Unknown parameter |month= ignored (help)
  8. ^ "LifeLine Therapeutics press release". October 16, 2003. Retrieved 08/19/2012. {{cite news}}: Check date values in: |accessdate= (help)
  9. ^ Bailey, Patrick. "The Uncertain Antiaging Pill". Betterhumans. Retrieved 11/29/2004. {{cite news}}: Check date values in: |accessdate= (help)
  10. ^ a b "Scientist returns to build long-life pill plant". The Scotsman. November 17, 2003. Retrieved 08/20/2012. {{cite news}}: Check date values in: |accessdate= (help)
  11. ^ a b Austin, Marsha (December 8, 2003). "Denver Businessmen Gamble on Selling Fountain of Youth in Pill Form". Denver Post. Retrieved 08/20/2012. {{cite news}}: Check date values in: |accessdate= (help)
  12. ^ "Some days it's just hard to believe". Footnoted. November 17, 2005. Retrieved 08/19/2012. {{cite news}}: Check date values in: |accessdate= (help)
  13. ^ "Lifeline Therapeutics CEO resigns". Denver Business Journal. July 5, 2005. Retrieved 08/20/2012. {{cite news}}: Check date values in: |accessdate= (help)
  14. ^ "Paul R. Myhill. RE: Resignation from the Board of Directors and Executive Committee of Lifeline Therapeutics, Inc (Form 8-K)". United States Securities and Exchange Commission. November 11, 2005. Retrieved 08/20/2012. {{cite news}}: Check date values in: |accessdate= (help)
  15. ^ "Protandim to be Available at General Nutrition Center (GNC) Stores". Lifeline Therapeutics press release. July 20, 2005. Retrieved 08/19/2012. {{cite news}}: Check date values in: |accessdate= (help)
  16. ^ "LifeVantage Corporation Appoints Industry Veteran David Brown as President & CEO (LFVN press release)". Reuters. January 14, 2008. Retrieved 08/24/2012. {{cite news}}: Check date values in: |accessdate= (help)
  17. ^ "The LifeVantage Story". LifeVantage, Inc. Retrieved 08/24/2012. David Brown, President of LifeVantage Network, recognized Protandim's potential. In a bold and daring move, he removed Protandim from retail shelves and in 2009 implemented a network marketing business method better suited to distribute Protandim and share its story. It was a new beginning for LifeVantage {{cite web}}: Check date values in: |accessdate= (help)
  18. ^ "LIFEVANTAGE CORP - 10KSB/A [Filed 06 January 2006]". sec.edgar-online.com. Retrieved 2011-02-05.
  19. ^ http://yahoo.brand.edgar-online.com/displayfilinginfo.aspx?FilingID=8164388-16511-132473&type=sect&dcn=0001193125-11-258536
  20. ^ "LifeVantage Corporation Announces Voluntary Recall and Replacement of Select Lots of Protandim® Dietary Supplement Due to Potential Health Risk" (Press release). December 5, 2012. Retrieved 12/07/2012. {{cite press release}}: Check date values in: |accessdate= (help)
  21. ^ "FAQ". protandim.com.
  22. ^ a b c Nelson, Sally K.; Bose, Swapan K.; Grunwald, Gary K.; Myhill, Paul; McCord, Joe M. (2006). "The induction of human superoxide dismutase and catalase in vivo: A fundamentally new approach to antioxidant therapy". Free Radical Biology and Medicine. 40 (2): 341–7. doi:10.1016/j.freeradbiomed.2005.08.043. PMID 16413416.
  23. ^ a b c "Protandim(R) does not influence alveolar epithelial permeability or intrapulmonary oxidative stress in human subjects with alcohol use disorders". Am J Physiol Lung Cell Mol Physiol. Jan 20. [Epub ahead of print]. 2012. PMID 22268125. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  24. ^ a b Velmurugan, K; Alam, J; McCord, J; Pugazhenthi, S (2009). "Synergistic induction of heme oxygenase-1 by the components of the antioxidant supplement Protandim". Free Radical Biology and Medicine. 46 (3): 430–40. doi:10.1016/j.freeradbiomed.2008.10.050. PMID 19056485.
  25. ^ a b Liu, Jianfeng; Gu, Xin; Robbins, Delira; Li, Guohong; Shi, Runhua; McCord, Joe M.; Zhao, Yunfeng (2009). "Protandim, a Fundamentally New Antioxidant Approach in Chemoprevention Using Mouse Two-Stage Skin Carcinogenesis as a Model". PLoS ONE. 4 (4): e5284. doi:10.1371/journal.pone.0005284. PMC 2668769. PMID 19384424.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  26. ^ a b Qureshi, Muhammad Muddasir; McClure, Warren C.; Arevalo, Nicole L.; Rabon, Rick E.; Mohr, Benjamin; Bose, Swapan K.; McCord, Joe M.; Tseng, Brian S. (2010). "The Dietary Supplement Protandim® Decreases Plasma Osteopontin and Improves Markers of Oxidative Stress in Muscular DystrophyMdxMice". Journal of Dietary Supplements. 7 (2): 159–178. doi:10.3109/19390211.2010.482041. PMC 2926985. PMID 20740052.
  27. ^ Hybertson BM, Gao B, Bose SK, McCord JM (2011 Oct 15. (Epub ahead of print)). "Oxidative stress in health and disease: The therapeutic potential of Nrf2 activation". Mol Aspects Med. 32 (4–6): 234–46. doi:10.1016/j.mam.2011.10.006. PMID 22020111. {{cite journal}}: Check date values in: |date= (help)CS1 maint: multiple names: authors list (link)
  28. ^ a b Donovan EL, McCord JM, Reuland DJ, Miller BF, Hamilton KL (2012). "Phytochemical activation of Nrf2 protects human coronary artery endothelial cells against an oxidative challenge". Oxid Med Cell Longev. 2012: Article ID 132931. doi:10.1155/2012/132931. PMID 22685617.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  29. ^ a b Bogaard, H. J.; Natarajan, R.; Henderson, S. C.; Long, C. S.; Kraskauskas, D.; Smithson, L.; Ockaili, R.; McCord, J. M.; Voelkel, N. F. (2009). "Chronic Pulmonary Artery Pressure Elevation Is Insufficient to Explain Right Heart Failure". Circulation. 120 (20): 1951–1960. doi:10.1161/CIRCULATIONAHA.109.883843. PMID 19884466.
  30. ^ a b Joddar, Binata; Reen, Rashmeet K.; Firstenberg, Michael S.; Varadharaj, Saradhadevi; McCord, Joe M.; Zweier, Jay L.; Gooch, Keith J. (2011). "Protandim attenuates intimal hyperplasia in human saphenous veins cultured ex vivo via a catalase-dependent pathway". Free Radical Biology and Medicine. 50 (6): 700–9. doi:10.1016/j.freeradbiomed.2010.12.008. PMID 21167278.
  31. ^ a b Reuland DJ, Khademi S, Castle CJ, Irwin DC, McCord JM, Miller BF, Hamilton KL. (2012). "Upregulation of phase II enzymes through phytochemical activation of Nrf2 protects cardiomyocytes against oxidant stress". Free Radical Biology and Medicine.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  32. ^ "FAQ". protandim.com.
  33. ^ Balogun E, Hoque M, Gong P, Killeen E, Green CJ, Foresti R, Alam J, Motterlini R (2003). "Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element". Biochem J. 371 (10): 887–95. doi:10.1042/BJ20021619. PMC 1223348. PMID 12570874.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  34. ^ Knasmüller, Siegfried; Nersesyan, Armen; Mišík, Miroslav; Gerner, Christopher; Mikulits, Wolfgang; Ehrlich, Veronika; Hoelzl, Christine; Szakmary, Akos; Wagner, Karl-Heinz (2008). "Use of conventional and -omics based methods for health claims of dietary antioxidants: a critical overview". British Journal of Nutrition. 99: ES3–52. doi:10.1017/S0007114508965752. PMID 18503734.
  35. ^ Hall, Harriet. "Pursued by Protandim Proselytizers". Science-Based Medicine. Retrieved 12 November 2011.
  36. ^ a b Robbins D, Zhao Y (23 March 2011). "The role of manganese superoxide dismutase in skin cancer". Enzyme Res. Epub: 409295. doi:10.4061/2011/409295. PMC 3092576. PMID 21603266.{{cite journal}}: CS1 maint: unflagged free DOI (link) Cite error: The named reference "robbins" was defined multiple times with different content (see the help page).
  37. ^ http://www.sciencedirect.com/science/article/pii/S0098299711000501
  38. ^ Vandenburgh H, Shansky J, Benesch-Lee F, Skelly K, Spinazzola JM, Saponjian Y, Tseng BS (2009). "Automated drug screening with contractile muscle tissue engineered from dystrophic myoblasts". FASEB J. 23 (10): 3325–34. doi:10.1096/fj.09-134411. PMID 19487307.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  39. ^ Harvey, Tom (12/23/2009). "Supplement company Zrii settles suits against rebellious ex-managers: LifeVantage pays $400,000 in dispute stemming from failed takeover attempt". Salt Lake Tribune. Retrieved 6 November 2011. {{cite web}}: Check date values in: |date= (help)
  40. ^ "Burke Hedges V. Lifevantage Corporation". United States District Court for the District of Utah: Civil No. 110918424. October 14, 2011. {{cite web}}: |access-date= requires |url= (help); Missing or empty |url= (help)
  41. ^ "Our case studies -- Protandim" (PDF). Primadonna Public Relations, Inc. Retrieved 08/12/2012. This Primadonna PR webpage shows Protandim as part of the company's portfolio of clients. Services provided by Primadonna included: "increased public awareness of the health supplement considerably through a strategic partnership with nationally recognized nutritionist and author Elizabeth Somer"; "successfully placed Protandim on 'Today' health segments—twice in one year—leading to dramatic spikes in Protandim's Web traffic"; "coordinated successful media tour during which Protandim was discussed on more than 20 local television and radio stations, including the nationally syndicated Health Radio Network; and "landed interview for Protandim scientist with More magazine, which resulted in coverage in an Anti-Aging special section." {{cite web}}: Check date values in: |accessdate= (help)
  42. ^ "Have you heard of a supplement called Protandim?". Elizabeth Somer Blog. Retrieved 08/19/2012. Somer states: "Not only have I heard of Protandim, but I was the spokesperson for the product the first year it came out. Dr. Joe McCord, the researcher that first discovered the antioxidant enzyme, superoxide dismutase, developed the supplement." {{cite web}}: Check date values in: |accessdate= (help)
  43. ^ "Lifeline Therapeutics, Inc. Form 8-K". United States Securities and Exchange Commission. November 21, 2006. Retrieved 08/19/2012. {{cite web}}: Check date values in: |accessdate= (help)
  44. ^ "Montel Williams and LifeVantage Corporation Sign License Agreement to Promote Science-Based Dietary Supplement Products". LifeVantage Press Release. Retrieved February 15, 2012.
  45. ^ "LFVN Form 8-K". SEC.gov. September 20, 2011. Retrieved November 7, 2011.
  46. ^ "Scientific Breakthrough. [Filed 21 July 2011]".
  47. ^ "The History of Free Radical Biology, Dr. Joe McCord [Filed 17 August 2011]". Retrieved 2012-08-13.
  48. ^ "Inside Protandim: The Paul Myhill Interview [Filed 09 March 2009]". Retrieved 2012-08-13.
  49. ^ "McCord Rejects Credit for Inventing Protandim [Filed 29 March 2005]". Joe McCord. Retrieved 2012-08-13.
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