Protandim

LifeVantage
Public
Traded as NASDAQ: LFVN
Industry Multi-level marketing
Founded 2003
Headquarters Salt Lake City, Utah, United States
Area served
 United States, Canada, Japan, Mexico, Australia, Hong Kong
Key people

Darren Jensen President, CEO

Robert M. Urban COO

Mark Jaggi CFO[1]

Joe M. McCord Chief Science Officer (retired)

Products Dietary supplements, skin care
Revenue Increase US$ 208.2 million (2013)[2]
US$ 12.1 million
Website www.lifevantage.com

Protandim is a patented[3] dietary supplement marketed by LifeVantage Corporation (NASDAQ: LFVN; formerly LifeLine Therapeutics, Lifeline Nutraceuticals, and Yaak River Resources, Inc), a Utah-based multi-level marketing company.[4] 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."[5]

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").[6][7][8][9][10][11][12] 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, and glutathione peroxidase, and to offset the ageing process.[11]

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-1152 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,[3] and it was officially launched in February 2005. Myhill and Driscoll resigned from the company later that year.[12][13][14][15]

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;[16] 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 multi-level marketing, selling it instead through a network of commissioned independent distributors. 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.[17][18]

Beginning in 2005, Protandim was produced under a manufacturing agreement with The Chemins Company of Colorado Springs, Colorado.[19] 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).[20]

In 2006, biochemist Joe M. McCord joined the LifeVantage board of directors as the company’s Director of Science.[21] McCord, who is listed by the SEC as a LifeVantage insider shareholder,[22] served as a spokesperson for Protandim and was responsible for distributor training and product research.[22] Under the terms of his 2011 employment agreement, McCord received $529,994 in direct compensation as well as a 50-cent commission on every bottle of Protandim sold.[23][24] During his tenure with the company, McCord co-authored 12 studies on Protandim.[25][26][27][28][29][30][31][32][33][34][35] He went on to serve as LifeVantage’s Chief Scientific Officer from June 2011 until September 2012, and then became a member of the company's science advisory board. LifeVantage announced McCord’s retirement in June 2013.[36][37] Under the terms of the separation agreement, McCord was to receive a payment of $1.7 million from the company.[37]

In January 2014, McCord was replaced by Shawn Talbott (developer of CortiSlim),[38] who served as the company's Chief Science Officer[39] until being relieved of his duties in June 2015[40] and replaced in August 2015 by Natalie Chevreau, who was hired as the company's Senior VP of Research and Development and is credited with the invention of the company's TruScience skin care product.[41]

Product invention

As recently as July 21, 2011, LifeVantage credited McCord as the creator of Protandim on its website.[42] 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.[43]

Voluntary recall

In December 2012, LifeVantage issued a voluntary recall of select lots (10 lots in total comprising 247,896 bottles) of Protandim due to potential health risks arising from the possible inclusion of small metal fragments in the final product.[44][45] In February 2013, the company announced that it was extending the recall to include additional lots of the product, estimating the total cost of the recall at $5.9 million.[46]

Composition

Protandim consists mainly of a blend of 5 herbal ingredients (amounts per caplet listed in parentheses):[26]

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.[47]

Research

Overview

Thirteen peer-reviewed research studies of Protandim have been published as of 2013; all but two[25][31] were conducted in in vitro or in vivo animal models. Twelve of the studies were conducted, authored, or co-authored and/or funded in whole or in part by LifeVantage and/or its employees, or by the company's predecessor, Lifeline Therapeutics.[25][26][27][28][29][30][31][32][33][34][35][35]

LifeVantage advertises Protandim as a Nrf2 activator.[48] 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.[49]

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.[50]

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."[51]

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 in red blood cells while reducing TBAR levels in blood plasma.[8][25]

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.[31] 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[26] and that intraperitoneal injection of an alcohol-based extract of Protandim could suppress skin tumor incidence in an experimental model in mice[27][52] and result in suppression of p53 and induction of MnSOD in isolated mouse epidermal cells in vitro.[53]

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.[35] 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 in isolated human coronary artery endothelial cells[32] and mouse cardiomyocytes in vitro.[33]

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.[28]

Other studies by McCord and colleagues have examined the effects of Protandim on fibrosis in a rodent model of Duchenne muscular dystrophy (DMD)[29] the effects of Protandim in an in vivo model of high altitude cerebral vascular leak,[34] 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.[54]

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.[55]

On October 14, 2011, Burke Hedges, a former LifeVantage distributor (hired for his background as a speaker and trainer) 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.[56]

References

  1. ↑ "Management Team". Livevantage.com. Retrieved 23 October 2015.
  2. ↑ "LifeVantage Announces Fourth Quarter and Full Fiscal Year 2013 Results". LifeVantage Corporation (press release). 12 September 2013. Retrieved 3 July 2014.
  3. 1 2 US 7241461, Myhill, Paul R. & William J. Driscoll, "Composition for alleviating inflammation and oxidative stress in a mammal.", issued 10 July 2007
  4. ↑ LifeVantage Corporation"FAQs - LifeVantage". Retrieved 4 July 2014.
  5. ↑ 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.
  6. ↑ "Lifeline Nutraceuticals, CereMedix sign agreement". Nutraceuticals World. December 1, 2003. Retrieved 2012-08-19.
  7. ↑ "The Uncertain Antiaging Pill (press release)". Betterhumans. December 1, 2004. Retrieved 2012-08-19.
  8. 1 2 Alison McCook (February 2006). "Your Money for Your Life". The Scientist. 20 (3): 33.
  9. ↑ "LifeLine Therapeutics press release". October 16, 2003. Retrieved 2012-08-19.
  10. ↑ Bailey, Patrick. "The Uncertain Antiaging Pill". Betterhumans. Archived from the original on December 4, 2004. Retrieved 2004-11-29.
  11. 1 2 "Scientist returns to build long-life pill plant". The Scotsman. November 17, 2003. Retrieved 2012-08-20.
  12. 1 2 Austin, Marsha (December 8, 2003). "Denver Businessmen Gamble on Selling Fountain of Youth in Pill Form". Denver Post. Retrieved 2012-08-20.
  13. ↑ "Some days it's just hard to believe". Footnoted. November 17, 2005. Retrieved 2012-08-19.
  14. ↑ "Lifeline Therapeutics CEO resigns". Denver Business Journal. July 5, 2005. Retrieved 2012-08-20.
  15. ↑ "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 2012-08-20.
  16. ↑ "Protandim to be Available at General Nutrition Center (GNC) Stores". Lifeline Therapeutics press release. July 20, 2005. Retrieved 2012-08-19.
  17. ↑ "LifeVantage Corporation Appoints Industry Veteran David Brown as President & CEO (LFVN press release)". Reuters. January 14, 2008. Retrieved 2012-08-24.
  18. ↑ "The LifeVantage Story". LifeVantage, Inc. Retrieved 2012-08-24. David Brown, President of LifeVantage Network, recognized Protandim's potential.
  19. ↑ "LIFEVANTAGE CORP - 10KSB/A [Filed 06 January 2006]". sec.edgar-online.com. Retrieved 2011-02-05.
  20. ↑ http://yahoo.brand.edgar-online.com/displayfilinginfo.aspx?FilingID=8164388-16511-132473&type=sect&dcn=0001193125-11-258536[]
  21. ↑ http://www.allbusiness.com/company-activities-management/board-management/5376294-1.html[]
  22. 1 2 http://secwatch.com/mccord-joe-m[]
  23. ↑ "LifeVantage Corp 10-K 2011". sec.edgar-online.com. Retrieved September 5, 2015.
  24. ↑ "Employment agreement with Dr. Joe McCord". U.S. Securities and Exchange Commission. April 1, 2011. Retrieved 2014-09-21.
  25. 1 2 3 4 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.
  26. 1 2 3 4 Velmurugan, Kalpana; Alam, Jawed; McCord, Joe M.; Pugazhenthi, Subbiah (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.
  27. 1 2 3 Liu, Jianfeng; Gu, Xin; Robbins, Delira; Li, Guohong; Shi, Runhua; McCord, Joe M.; Zhao, Yunfeng (2009). Bauer, Joseph Alan, ed. "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 2668769Freely accessible. PMID 19384424.
  28. 1 2 3 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): 1951–60. doi:10.1161/CIRCULATIONAHA.109.883843. PMID 19884466.
  29. 1 2 3 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 2926985Freely accessible. PMID 20740052.
  30. 1 2 3 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. 1 2 3 4 Burnham, Ellen L.; McCord, Joe M.; Bose, Swapan; Brown, Lou Ann S.; House, Robert; Moss, Marc; Gaydos, Jeanette (2012). "Protandim does not influence alveolar epithelial permeability or intrapulmonary oxidative stress in human subjects with alcohol use disorders". American Journal of Physiology. Lung Cellular and Molecular Physiology. 302 (7): L688–99. doi:10.1152/ajplung.00171.2011. PMC 3330762Freely accessible. PMID 22268125.
  32. 1 2 3 Donovan, Elise L.; McCord, Joe M.; Reuland, Danielle J.; Miller, Benjamin F.; Hamilton, Karyn L. (2012). "Phytochemical Activation of Nrf2 Protects Human Coronary Artery Endothelial Cells against an Oxidative Challenge". Oxidative Medicine and Cellular Longevity. 2012: 1. doi:10.1155/2012/132931. PMC 3364676Freely accessible. PMID 22685617.
  33. 1 2 3 Reuland, Danielle J.; Khademi, Shadi; Castle, Christopher J.; Irwin, David C.; McCord, Joe M.; Miller, Benjamin F.; Hamilton, Karyn L. (2013). "Upregulation of phase II enzymes through phytochemical activation of Nrf2 protects cardiomyocytes against oxidant stress". Free Radical Biology and Medicine. 56: 102–11. doi:10.1016/j.freeradbiomed.2012.11.016. PMID 23201694.
  34. 1 2 3 Lisk C, McCord J, Bose S, Sullivan T, Loomis Z, Nozik-Grayck E, Schroeder T, Hamilton K, Irwin DC (May 27, 2013). "Nrf2 Activation: A potential strategy for the prevention of Acute Mountain Sickness". Free Radic Biol Med. pii: S0891-5849(13)00234-7: 264–73. doi:10.1016/j.freeradbiomed.2013.05.024. PMID 23722164.
  35. 1 2 3 4 Hybertson, Brooks M.; Gao, Bifeng; Bose, Swapan K.; McCord, Joe M. (2011). "Oxidative stress in health and disease: The therapeutic potential of Nrf2 activation". Molecular Aspects of Medicine. 32 (4–6): 234–46. doi:10.1016/j.mam.2011.10.006. PMID 22020111.
  36. ↑ http://globenewswire.com/news-release/2013/06/25/556132/10037495/en/Dr-Joe-McCord-LifeVantage-Corporation-s-First-Chief-Science-Officer-Retires-From-Company.html[]
  37. 1 2 "Form 8-K for LifeVantage Corp". Yahoo.com. June 25, 2013. Retrieved 10 November 2013.
  38. ↑ "Three Cortislim Defendants to Give up $4.5 Million in Cash and Other Assets". Federal Trade Commission. September 21, 2005. Retrieved July 14, 2016.
  39. ↑ "LifeVantage Corporation Appoints Shawn Talbott Ph.D. as New Global Chief Science Officer". LifeVantage, Inc. January 7, 2014. Retrieved July 14, 2016.
  40. ↑ Shawn M. Talbott (July 13, 2015). "My New Gig?". Shawn M. Talbott Personal Blog. Retrieved July 14, 2016.
  41. ↑ "Patent WO 2015164504 A1: Topical compositions and methods for reducing oxidative stress". October 29, 2015. Retrieved July 14, 2016.
  42. ↑ "Scientific Breakthrough. [Filed 21 July 2011]".
  43. ↑ "The History of Free Radical Biology, Dr. Joe McCord [Filed 17 August 2011]". Retrieved 2012-08-13.
  44. ↑ "LifeVantage Corporation Announces Voluntary Recall and Replacement of Select Lots of Protandim® Dietary Supplement Due to Potential Health Risk" (Press release). 5 December 2012. Retrieved 7 December 2012.
  45. ↑ "Enforcement Report - Week of January 16, 2013". U.S. Food and Drug Administration. Retrieved 10 August 2013.
  46. ↑ "Form 8-K for LifeVantage Corp". yahoo.brand.edgar-online.com/. February 13, 2013. Retrieved July 11, 2016.
  47. ↑ "FAQ". protandim.com.
  48. ↑ "FAQ". protandim.com.
  49. ↑ Balogun, Elisabeth; Hoque, Martha; Gong, Pengfei; Killeen, Erin; Green, Colin J.; Foresti, Roberta; Alam, Jawed; Motterlini, Roberto (2003). "Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element". Biochemical Journal. 371 (3): 887–95. doi:10.1042/BJ20021619. PMC 1223348Freely accessible. PMID 12570874.
  50. ↑ 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.
  51. ↑ Hall, Harriet. "Pursued by Protandim Proselytizers". Science-Based Medicine. Retrieved 12 November 2011.
  52. ↑ Robbins, Delira; Zhao, Yunfeng (2011). "The Role of Manganese Superoxide Dismutase in Skin Cancer". Enzyme Research. 2011: 1. doi:10.4061/2011/409295. PMC 3092576Freely accessible. PMID 21603266.
  53. ↑ Robbins, Delira; Gu, Xin; Shi, Runhua; Liu, Jianfeng; Wang, Fei; Ponville, Jacqulyne; McCord, Joe M.; Zhao, Yunfeng (2010). Delprato, Anna Maria, ed. "The Chemopreventive Effects of Protandim: Modulation of p53 Mitochondrial Translocation and Apoptosis during Skin Carcinogenesis". PLoS ONE. 5 (7): e11902. doi:10.1371/journal.pone.0011902. PMC 2912769Freely accessible. PMID 20689586.
  54. ↑ Vandenburgh, Herman; Shansky, Janet; Benesch-Lee, Frank; Skelly, Kirsten; Spinazzola, Janelle M.; Saponjian, Yero; Tseng, Brian S. (2009). "Automated drug screening with contractile muscle tissue engineered from dystrophic myoblasts". The FASEB Journal. 23 (10): 3325–34. doi:10.1096/fj.09-134411. PMC 3236595Freely accessible. PMID 19487307.
  55. ↑ Harvey, Tom (2009-12-23). "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.
  56. ↑ "Burke Hedges V. Lifevantage Corporation". United States District Court for the District of Utah: Civil No. 110918424. October 14, 2011.
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