Anthony Almada 10.01.04
"Life is too short to be small." This call to muscular arms was emblazoned on one "muscle gear" marketer's T-shirts offered for sale in the early 1990s. As we enter the middle of the first decade of the 21st century the sports nutrition industry is displaying signs of both regression and progression. Regulatory forces have been marshaled and deployed, with sniper precision and episodic frequency. Cornerstone bioactive ingredients have hit their zenith and then been plucked from the sky, or had a laser lock placed on their tail. Political bantering has morphed into political bill-slinging, often infused with ignorance and an ultra-anemic evidence base. Science has once again been stretched and tortured to tell tales that are tall and leave a taint. Patents have been issued but their respective offensive plans have frequently been lax or absent.
Despite the challenges, charlatans and charades, the sports nutrition category continues to economically thrive and grow, bested only by weight loss and energy drinks. According to Nutrition Business Journal, San Diego, CA, sports and energy bars accounted for $2.3 billion in consumer sales in 2003, a 26% jump from 2002, surpassed only by sports and energy beverages (inclusive of Gatorade and Red Bull), which posted $4.8 billion in sales, representing 10% growth. "Core" sports nutrition bodybuilder-type products showed less robust growth and far less consumption: $140 million for core prepared "muscle" and protein drinks (+4%); $1.66 billion for powdered products, including protein powders (+8%); and $110 million for solid dose forms, including capsules and tablets (+8%). Let's use both the 50,000 feet spy camera and electron microscope to take a bigger and closer look.
The conundrum confronting a landscape assessment of the sports nutrition market is that no definitive lines of demarcation exist. Do we exclude isotonic drinks like Gatorade (now in India and adulating soccer legend Mia Hamm) and Powerade and basketball teen pre-legend LeBron James' self-designed FLAVA23? Should "energy bars" like Powerbar or Balance Bar Gold, with its clinical research-confirmed low glycemic response be included? What about weight loss products outside of Slim-Fast, e.g. claimed thermogenic agents?
Sports nutrition has traversed the bright line of primarily core physique enthusiasts and gone mainstream for quite some time. The introduction of the patent pending protein-enriched Snickers Marathon bar by M&M Mars, McLean, VA, at the American College of Sports Medicine a few years ago, the launch of Everlast branded supplements (solid dose forms, bars, and powders, all sporting generic compositions) by Vitamin Branding Corporation, New York, NY, into the mass market, and the media pick-up and embrace of AgelessXtra, a fruit-based ready-to-drink (RTD) product claiming concentration- and mobility enhancement (yet lacking any product specific independent placebo-controlled clinical trials demonstrating such) for aging professional golfers promoted by multi-level marketer Oasis Wellness Network/Unigen, Olympia, WA, are only three examples of the once bright line being obscured and blurring.
Link the aforementioned product examples to the end user base that now includes substantial numbers of adolescent boys seeking the over-the-counter (OTC) equivalent of growth hormone and steroids, in addition to baby boomer men and women aspiring to muscular performance and physique peaks, and the blur is broadened. Sports nutrition is no longer limited to the "gym rats" or core element of the physique enthusiast community. "Sports nutrition" is herein defined as the acute or chronic practice of orally ingesting a packaged consumer good with the intent of augmenting one's physical performance or ability ("ergogenic" aid), muscle mass, or recuperative/adaptive response to vigorous physical activity, and it is approaching the mainstream adoption of Starbucks coffee. And a cup of caffeine-rich coffee itself could be considered a "sports nutrition" RTD.
The October 1994 enactment of the Dietary Supplement Health & Education Act (DSHEA)-almost 18 months after creatine began its meteoric rise into sports nutrition stardom-heralded a new vista for the sports nutrition industry. The onus of regulatory fiat by FDA and the ostensible marketing might of structure/function claims was embraced and swallowed. Ephedra was added to everything but drinking water and DHEA evolved into what was claimed to be a super testosterone precursor named androstenedione (andro)-based upon a clinical study conducted in women.
In March this year, FDA executed a "crackdown" on andro when this non-anabolic steroid had been lingering at its sales nadir and been replaced by far more chemically adventurous steroids. The ban and warning letters issued to 23 presumed andro marketers elicited jeering comments from the OTC steroid marketers, who had long moved onto the next two-three generations of steroidal agents. Stan Antosh, a senior executive at OSMO, San Francisco, CA, offered the following juxtaposition in the March 18, 2004 issue of the Washington Post: "It's like a brand new Porsche with two turbo chargers versus a broken down Volkswagen on cement blocks with no tires." In the same article Jim Riggs, president of Schwartz Laboratories, Cincinnati, OH, asserted, "The FDA is so behind the gamethe technology is so far advanced past androstenedione." Pending legislation (S. 2195 and H.R. 3866; Anabolic Steroid Control Acts) would require the listing of andro and other steroid hormones that are in vogue (with the exception of DHEA), which may attenuate the flippancy of the comments of current OTC steroids marketers with still unsubstantiated anabolic efficacy in humans. Add in the international media story behind Victor Conte of BALCO, San Francisco, CA, (the inventor behind dietary supplement ZMA, recent independent studies suggesting it is not effective at enhancing strength or muscle mass) and his alleged distribution of the steroid tetrahydrogestrinone (THG) to elite athletes further fuels the drug-"andro" fire.
Speed and regulatory actions by FDA (and FTC) do not appear to coexist. Rogue marketers making wholly unsubstantiated claims populate the online, on air and in-print worlds. Even automobile and surfing magazines run ads claiming muscle and strength building properties of dietary supplements that have a paucity of suggestive evidence, at best.
However, the FDA's recent harnessing of the New Dietary Ingredient (NDI) provision of DSHEA to ban androstenedione may prove increasingly thwarting to new product development. A New Dietary Ingredient is defined as one that was not lawfully marketed prior to October 15, 1994, or is consumed in a food form that has been chemically altered, and must demonstrate a safe history of use or scientific evidence of safety at the intended level of use prior to its lawful marketing. The common perception is that if an ingredient is simply present in a food, e.g. octopamine or evodiamine, one can market it and its parent biomass under an Old Dietary Ingredient provision. Given the landmark Pharmanex v. Shalala case, the food containing the substance of interest must be marketed for said substance, e.g. Seville orange juice or orange marmalade for synephrine content or Evodia fruit for evodiamine content.
Recent NDI rejections have also ventilated ostensibly airtight submissions. A submission for creatine ethyl ester (Pro-Nutrient Technologies, started by a pharmacologist from the University of Nebraska, and the recipient of NCCAM funds in 2002), was rejected (in 2002 and again in 2003) for a complete absence, or insufficient amount, of safety data, or the position that the ingredient does not meet the definition of a "dietary ingredient" (GNC had this product under consideration for distribution earlier this year). This patented form of creatine is claimed to be superior to generic creatine monohydrate, with any controlled animal and clinical safety and efficacy data being in absentia. (Note: Other marketers have been selling creatine ester-containing products, without filing an NDI submission and receiving a notice of allowance.)
The purported endurance enhancing agent fructose 1,6-diphosphate (marketed by AHD International, Atlanta, GA) was rejected on the grounds that it is the subject of an investigational new drug (IND).
An arginine-HMB complex (Innovative Supplement Concepts, Dunmore, PA) was rejected because its dietary ingredient definition was obscure and no safety data on the ingredient were provided in the submission (Note: HMB, as the calcium salt, has been shown to increase muscle mass and performance in untrained individuals, in studies conducted mostly by individuals with an economic interest in the sale of the ingredient. Other studies have shown that it provides little or no benefit for already trained individuals. The company that markets HMB, Metabolic Technologies Inc. (MTI), an Iowa State University-spawned business entity, also markets a product called Juven, which is an admixture of L-arginine, L-glutamine and calcium HMB. It is likely that the arginine-HMB complex was conceived to circumvent the HMB patent suite owned by MTI.)
The NDI "stick" may be wielded with greater frequency by FDA, suggesting that any marketers considering capital investments (R&D, patents, and/or marketing) in NDI's or products containing such obtain expert legal counsel before making the investment. A well-rounded critical review on this topic has been published by Pat and Chris Noonan, a food and drug attorney and former dietary supplement company executive, and a public health nutritionist with abundant marketing savvy, respectively, in HerbalGram (2004;63:70-74).
The tectonic plate shift caused by the banning of virtually all dietary supplements containing ephedrine alkaloids sold in the U.S. has fostered a furious quest for an "ephedra substitute." The findings of a meta-analysis in JAMA (March 26, 2003; "RAND Report") that the claims of ephedra being ergogenic were wholly unsubstantiated, and that the efficacy of synthetic ephedrine (with or without caffeine) was limited to single, acute dosing added injury to the economic insult of the 2004 ban. Of all the scions of ephedra, the one most frequently used in its place has been synephrine and its biomass source, Citrus aurantium. There appear to be no placebo-controlled, financially independent studies that have shown synephrine, octopamine, hordenine, or tyramine, or any C. aurantium extract to have any ergogenic or physique-enhancing effects. A recent review on C. aurantium by Georgetown University researchers (Exp Biol Med, 2004; 229:698704.) engendered the ire of the American Herbal Products Association (AHPA), Silver Spring, MD, because of the article's assertion that it may foster blood pressure elevation or dangerous elevations in the blood concentrations of certain drugs. However, AHPA did not challenge the conclusion that C. aurantium lacked any evidence of efficacy (specifically related to weight loss). Indeed, the article points out that octopamine, advocated by some companies (in its pure form) as being superior to synephrine, has been shown to be ineffective in human fat cells (synephrine is mildly effective).
One of the strongest-selling offspring of creatine was ATP Advantage Creatine Serum, launched by Muscle Marketing USA, Blaine, WA, in January of 1996. At the time, creatine was believed to be unstable in any solution with even a mildly acidic profile (virtually all flavored liquids/drinks have a slightly to moderately acidic pH). The promise of a "stable" creatine liquid that was superior to conventional creatine powders and without the side effects, coupled with a prodigious and seemingly relentless marketing, promotional and advertising campaigns, facilitated the growth of Creatine Serum into a formidable brand with a variety of line extensions. However, a series of chemical analyses, and later human pharmacokinetic, muscle biopsy and muscular performance studies, completely refuted the claims of 2.5 grams of creatine/serving and its ability to increase muscle creatine. What is provocative is that some of the largest retail marketers of this product were made aware of this data from 2001 forward but continued to offer the product for sale while preventing other companies with far less contentious products from being accepted for distribution.
Degussa Bioactives, Atlanta, GA, manufacturer and marketer of CreaPure brand creatine monohydrate, filed a federal suit against Muscle Marketing USA (MMUSA) in 2002, which ultimately resulted in a permanent injunction against the defendant, preventing them from making any comparison of its product to creatine powder products. No injunction was made in relation to the verity of MMUSA's claims for its own product. However, in July of this year the New Zealand Commerce Commission prevailed in obtaining a fine of $70,000 (NZ) for breaching the Fair Trading Act and making false claims about its ATP Advantage Creatine Serum product. The judge stated, "The company was highly culpable. On a scale of 1-10 it was 8." The New Zealand subsidiary of MMUSA liquidated its assets this past May.
Another category-creating product was NO2, marketed by MRI, Burlingame, CA, and led by EAS co-founder Ed Byrd. The product is a controlled-release composition of the amino acid complex arginine alpha-ketoglutarate. An exclusive distribution relationship with GNC, and an aggressive advertising and marketing in-store and in-print campaign, led to substantial sales of the product, while no controlled clinical trial evidence existed to support claims of increased muscle growth, strength, endurance, muscle hardness/"pump" or sexual performance. A study recently presented at the first International Society of Sports Nutrition (Sports Nutr Rev J, 1:S1-14, 2004; www.sportsnutritionsociety.org), led by Dr. Rick Kreider at Baylor University, did show that daily doses of the product (12 grams per day for eight weeks in resistance-trained males) led to significant increases in maximal single repetition bench press and stationary cycling sprint performance, but proved no better than placebo in relation to muscle or fat mass changes, treadmill endurance, leg extension performance or self-reported measures of sexual function or muscle hardness. It will be interesting to see how these results, contrasted with the backdrop of a legacy of far more aggressive on- and off label claims, will be portrayed by GNC, its publications and in other publications.
The allure of issued patents on compositions, and to a lesser extent, methods of use, for nutraceutical products has enjoyed incremental magnification over the past several years. Seminal examples of patents germane to sports nutrition products and with teeth, i.e. vigilant enforcement campaigns, include HMB (MTI) and chromium picolinate (Nutrition 21, Purchase, NY; prior to the composition of matter patent expiring). Hundreds of patents (issued and pending) claim compositions intended to function as a sports nutrition product. On- and off-label claims of "patented" or "patent pending" continue to become more and more hollow as a fewer and fewer percentage of issued patents are enforced.
Two examples of long infringed patents are both assigned to Muscletech and relating to food supplements containing creatine and a form of lipoic acid or carbohydrates (or any composition that can increase insulin concentrations in the blood, e.g. protein), both as embodied in Muscletech's Cell-Tech product. Numerous companies have been marketing apparently infringing compositions for several years. The creatine-carbohydrate/insulin boosting patent was acquired by Muscletech from the University of Nottingham, its lead inventor being Dr. Paul Greenhaff.
Competitive insulation can be achieved via other means. Case in point is Gatorade and its "35 years of research." The category-creating position, nearly global distribution of the product, and the strong unaided consumer recall of the brand are pivotal elements in its domination of the energy drinks category. This is contrasted to Red Bull, which enjoys a suite of several published clinical trials describing its ergogenic and alertness-enhancing effects, albeit without the ideal control comparisons. The sponsorship activities of Red Bull in motorsports, especially the largest viewed sport on a global scale-Formula 1-helped catapult it past the $1 billion sales mark in 2003, undoubtedly assisted by its popularity in the nocturnal "hydration sportspersons" that frequent night clubs and bars.
A new contender in the energy drinks category hails from Pacific Health Labs, Matawan, NJ. Accelerade, an RTD beverage or ready-to-mix (RTM) powder (both combine carbohydrates + protein) initially positioned for the endurance activity individual, has attempted to erode the prestige and perception of Gatorade (a protein-free beverage/RTM) by sponsoring head-to-head comparison studies at high profile university laboratories and yielding superior results. Endurox R4 is an RTM that leverages a 4:1 ratio of carbohydrates to protein, with some evidence showing increased muscle glycogen repletion following intensive exercise. These products (with a patent and patents pending) were launched with a mass market focus and may build a more infectious viral marketing network and sales velocity if they were repositioned for the core enthusiast. GNC ex-CEO Greg Horn is on the board of the company and may be able to redirect the ship as he did with finesse and aplomb while at the helm of GNC. What will be of additional interest is whether competitor companies will engage in duplicative distraction and elicit patent infringement suits or even claim patent invalidity because of prior art.
It is important to note that U.S. patent law is more lax in its requirement of "data" proving the claims in a patent application. Indeed, in the majority of nutraceutical-centric patents issued NO proof of concept data (in animals or humans) is provided, let alone placebo-controlled, randomized trials. In the U.S. patent system, having a patent on a nutraceutical composition is tantamount to owning a plot of land with no access to water or utilities-it has very little value until its "utility" and "viability" are confirmed despite one still being able to claim they are "land rich."
The sports nutrition market landscape is convoluted, heavily fragmented, and dotted with an increasing number of threats to those that stray outside of the operating boundaries. Product- or ingredient-specific clinical science still marks an infinitesimally small number, while claims and stories by raconteurs and "experts" alike abound. The drive for clinical research substantiation of products and ingredients is indeed compelling more companies to make the investment and take the risk (as they do with advertising and marketing campaigns), but also is fostering a graveyard of undisclosed studies with "non-positive" results. Among the companies that invest in real science and IP (intellectual property), the challenge is to exploit the investment and maintain leader market share, even a category monopoly.
The remainder of this decade will likely unfold with more regulatory enforcement, greater political heat and a thicker cloth being woven that attempts to (spuriously) link illicit ergogenic and anabolic synthetic agents and OTC dietary supplements and even some foods and beverages. With the physiques of certain sportswomen and sportsmen being exalted to an extent that parallels their respective physical talents, questions about "drug-free" will carry on as the Anti-Doping Agency continues its push for aggressive testing and action.
Several years ago we successfully defended a prominent professional football player who had failed a drug test, his urine reflecting use of the anabolic steroid nandrolone, or (as we asserted) ingestion of an OTC dietary supplement steroid that was not on the NFL banned substances list. Today, claiming a dietary supplement caused a failed drug test rarely is a viable defense. What remains enigmatic is why an athlete such as a baseball player can be instantly suspended for using cork in a bat or Vaseline on a baseball but still continue to play if caught using true anabolic steroids or growth hormone. To achieve the rarefied status of being safe and effective the sports nutrition industry needs to put its money where its muscles are and use a strong evidence base to combat the relentless skepticism that it invites. NW
About the author:
Mr. Almada is the co-founder of Experimental and Applied Sciences (EAS), the president and chief scientific officer of IMAGINutrition, Inc., Laguna Niguel, CA, a founding partner in Mercura, LLC (www.mercuraip.com), and is a regular columnist ("Proprietary Perspectives") for Nutraceuticals World. He can be reached at 949-363-5858; Fax: 949-363-1758; E-mail: anthony@imaginutrition.com; Website: www.imaginutrition.com.
Disclosure: Mr. Almada is on the editorial advisory board of Nutrition Business Journal, is a consultant to Nutrition 21, receives royalty payments from iSatori from the sales of Meta-CEL, a creatine/D-pinitol product, and still takes creatine (as Meta-CEL) on a daily basis.
Despite the challenges, charlatans and charades, the sports nutrition category continues to economically thrive and grow, bested only by weight loss and energy drinks. According to Nutrition Business Journal, San Diego, CA, sports and energy bars accounted for $2.3 billion in consumer sales in 2003, a 26% jump from 2002, surpassed only by sports and energy beverages (inclusive of Gatorade and Red Bull), which posted $4.8 billion in sales, representing 10% growth. "Core" sports nutrition bodybuilder-type products showed less robust growth and far less consumption: $140 million for core prepared "muscle" and protein drinks (+4%); $1.66 billion for powdered products, including protein powders (+8%); and $110 million for solid dose forms, including capsules and tablets (+8%). Let's use both the 50,000 feet spy camera and electron microscope to take a bigger and closer look.
Is There a Bright Line?
The conundrum confronting a landscape assessment of the sports nutrition market is that no definitive lines of demarcation exist. Do we exclude isotonic drinks like Gatorade (now in India and adulating soccer legend Mia Hamm) and Powerade and basketball teen pre-legend LeBron James' self-designed FLAVA23? Should "energy bars" like Powerbar or Balance Bar Gold, with its clinical research-confirmed low glycemic response be included? What about weight loss products outside of Slim-Fast, e.g. claimed thermogenic agents?
Sports nutrition has traversed the bright line of primarily core physique enthusiasts and gone mainstream for quite some time. The introduction of the patent pending protein-enriched Snickers Marathon bar by M&M Mars, McLean, VA, at the American College of Sports Medicine a few years ago, the launch of Everlast branded supplements (solid dose forms, bars, and powders, all sporting generic compositions) by Vitamin Branding Corporation, New York, NY, into the mass market, and the media pick-up and embrace of AgelessXtra, a fruit-based ready-to-drink (RTD) product claiming concentration- and mobility enhancement (yet lacking any product specific independent placebo-controlled clinical trials demonstrating such) for aging professional golfers promoted by multi-level marketer Oasis Wellness Network/Unigen, Olympia, WA, are only three examples of the once bright line being obscured and blurring.
Link the aforementioned product examples to the end user base that now includes substantial numbers of adolescent boys seeking the over-the-counter (OTC) equivalent of growth hormone and steroids, in addition to baby boomer men and women aspiring to muscular performance and physique peaks, and the blur is broadened. Sports nutrition is no longer limited to the "gym rats" or core element of the physique enthusiast community. "Sports nutrition" is herein defined as the acute or chronic practice of orally ingesting a packaged consumer good with the intent of augmenting one's physical performance or ability ("ergogenic" aid), muscle mass, or recuperative/adaptive response to vigorous physical activity, and it is approaching the mainstream adoption of Starbucks coffee. And a cup of caffeine-rich coffee itself could be considered a "sports nutrition" RTD.
Regulatory Rigor: A Wrist Slap on Steroids
The October 1994 enactment of the Dietary Supplement Health & Education Act (DSHEA)-almost 18 months after creatine began its meteoric rise into sports nutrition stardom-heralded a new vista for the sports nutrition industry. The onus of regulatory fiat by FDA and the ostensible marketing might of structure/function claims was embraced and swallowed. Ephedra was added to everything but drinking water and DHEA evolved into what was claimed to be a super testosterone precursor named androstenedione (andro)-based upon a clinical study conducted in women.
In March this year, FDA executed a "crackdown" on andro when this non-anabolic steroid had been lingering at its sales nadir and been replaced by far more chemically adventurous steroids. The ban and warning letters issued to 23 presumed andro marketers elicited jeering comments from the OTC steroid marketers, who had long moved onto the next two-three generations of steroidal agents. Stan Antosh, a senior executive at OSMO, San Francisco, CA, offered the following juxtaposition in the March 18, 2004 issue of the Washington Post: "It's like a brand new Porsche with two turbo chargers versus a broken down Volkswagen on cement blocks with no tires." In the same article Jim Riggs, president of Schwartz Laboratories, Cincinnati, OH, asserted, "The FDA is so behind the gamethe technology is so far advanced past androstenedione." Pending legislation (S. 2195 and H.R. 3866; Anabolic Steroid Control Acts) would require the listing of andro and other steroid hormones that are in vogue (with the exception of DHEA), which may attenuate the flippancy of the comments of current OTC steroids marketers with still unsubstantiated anabolic efficacy in humans. Add in the international media story behind Victor Conte of BALCO, San Francisco, CA, (the inventor behind dietary supplement ZMA, recent independent studies suggesting it is not effective at enhancing strength or muscle mass) and his alleged distribution of the steroid tetrahydrogestrinone (THG) to elite athletes further fuels the drug-"andro" fire.
Speed and regulatory actions by FDA (and FTC) do not appear to coexist. Rogue marketers making wholly unsubstantiated claims populate the online, on air and in-print worlds. Even automobile and surfing magazines run ads claiming muscle and strength building properties of dietary supplements that have a paucity of suggestive evidence, at best.
However, the FDA's recent harnessing of the New Dietary Ingredient (NDI) provision of DSHEA to ban androstenedione may prove increasingly thwarting to new product development. A New Dietary Ingredient is defined as one that was not lawfully marketed prior to October 15, 1994, or is consumed in a food form that has been chemically altered, and must demonstrate a safe history of use or scientific evidence of safety at the intended level of use prior to its lawful marketing. The common perception is that if an ingredient is simply present in a food, e.g. octopamine or evodiamine, one can market it and its parent biomass under an Old Dietary Ingredient provision. Given the landmark Pharmanex v. Shalala case, the food containing the substance of interest must be marketed for said substance, e.g. Seville orange juice or orange marmalade for synephrine content or Evodia fruit for evodiamine content.
Recent NDI rejections have also ventilated ostensibly airtight submissions. A submission for creatine ethyl ester (Pro-Nutrient Technologies, started by a pharmacologist from the University of Nebraska, and the recipient of NCCAM funds in 2002), was rejected (in 2002 and again in 2003) for a complete absence, or insufficient amount, of safety data, or the position that the ingredient does not meet the definition of a "dietary ingredient" (GNC had this product under consideration for distribution earlier this year). This patented form of creatine is claimed to be superior to generic creatine monohydrate, with any controlled animal and clinical safety and efficacy data being in absentia. (Note: Other marketers have been selling creatine ester-containing products, without filing an NDI submission and receiving a notice of allowance.)
The purported endurance enhancing agent fructose 1,6-diphosphate (marketed by AHD International, Atlanta, GA) was rejected on the grounds that it is the subject of an investigational new drug (IND).
An arginine-HMB complex (Innovative Supplement Concepts, Dunmore, PA) was rejected because its dietary ingredient definition was obscure and no safety data on the ingredient were provided in the submission (Note: HMB, as the calcium salt, has been shown to increase muscle mass and performance in untrained individuals, in studies conducted mostly by individuals with an economic interest in the sale of the ingredient. Other studies have shown that it provides little or no benefit for already trained individuals. The company that markets HMB, Metabolic Technologies Inc. (MTI), an Iowa State University-spawned business entity, also markets a product called Juven, which is an admixture of L-arginine, L-glutamine and calcium HMB. It is likely that the arginine-HMB complex was conceived to circumvent the HMB patent suite owned by MTI.)
The NDI "stick" may be wielded with greater frequency by FDA, suggesting that any marketers considering capital investments (R&D, patents, and/or marketing) in NDI's or products containing such obtain expert legal counsel before making the investment. A well-rounded critical review on this topic has been published by Pat and Chris Noonan, a food and drug attorney and former dietary supplement company executive, and a public health nutritionist with abundant marketing savvy, respectively, in HerbalGram (2004;63:70-74).
The Ephedra Void: The Emperor is Still Unclothed
The tectonic plate shift caused by the banning of virtually all dietary supplements containing ephedrine alkaloids sold in the U.S. has fostered a furious quest for an "ephedra substitute." The findings of a meta-analysis in JAMA (March 26, 2003; "RAND Report") that the claims of ephedra being ergogenic were wholly unsubstantiated, and that the efficacy of synthetic ephedrine (with or without caffeine) was limited to single, acute dosing added injury to the economic insult of the 2004 ban. Of all the scions of ephedra, the one most frequently used in its place has been synephrine and its biomass source, Citrus aurantium. There appear to be no placebo-controlled, financially independent studies that have shown synephrine, octopamine, hordenine, or tyramine, or any C. aurantium extract to have any ergogenic or physique-enhancing effects. A recent review on C. aurantium by Georgetown University researchers (Exp Biol Med, 2004; 229:698704.) engendered the ire of the American Herbal Products Association (AHPA), Silver Spring, MD, because of the article's assertion that it may foster blood pressure elevation or dangerous elevations in the blood concentrations of certain drugs. However, AHPA did not challenge the conclusion that C. aurantium lacked any evidence of efficacy (specifically related to weight loss). Indeed, the article points out that octopamine, advocated by some companies (in its pure form) as being superior to synephrine, has been shown to be ineffective in human fat cells (synephrine is mildly effective).
Innovation, Invention or Incredulous?
One of the strongest-selling offspring of creatine was ATP Advantage Creatine Serum, launched by Muscle Marketing USA, Blaine, WA, in January of 1996. At the time, creatine was believed to be unstable in any solution with even a mildly acidic profile (virtually all flavored liquids/drinks have a slightly to moderately acidic pH). The promise of a "stable" creatine liquid that was superior to conventional creatine powders and without the side effects, coupled with a prodigious and seemingly relentless marketing, promotional and advertising campaigns, facilitated the growth of Creatine Serum into a formidable brand with a variety of line extensions. However, a series of chemical analyses, and later human pharmacokinetic, muscle biopsy and muscular performance studies, completely refuted the claims of 2.5 grams of creatine/serving and its ability to increase muscle creatine. What is provocative is that some of the largest retail marketers of this product were made aware of this data from 2001 forward but continued to offer the product for sale while preventing other companies with far less contentious products from being accepted for distribution.
Degussa Bioactives, Atlanta, GA, manufacturer and marketer of CreaPure brand creatine monohydrate, filed a federal suit against Muscle Marketing USA (MMUSA) in 2002, which ultimately resulted in a permanent injunction against the defendant, preventing them from making any comparison of its product to creatine powder products. No injunction was made in relation to the verity of MMUSA's claims for its own product. However, in July of this year the New Zealand Commerce Commission prevailed in obtaining a fine of $70,000 (NZ) for breaching the Fair Trading Act and making false claims about its ATP Advantage Creatine Serum product. The judge stated, "The company was highly culpable. On a scale of 1-10 it was 8." The New Zealand subsidiary of MMUSA liquidated its assets this past May.
Another category-creating product was NO2, marketed by MRI, Burlingame, CA, and led by EAS co-founder Ed Byrd. The product is a controlled-release composition of the amino acid complex arginine alpha-ketoglutarate. An exclusive distribution relationship with GNC, and an aggressive advertising and marketing in-store and in-print campaign, led to substantial sales of the product, while no controlled clinical trial evidence existed to support claims of increased muscle growth, strength, endurance, muscle hardness/"pump" or sexual performance. A study recently presented at the first International Society of Sports Nutrition (Sports Nutr Rev J, 1:S1-14, 2004; www.sportsnutritionsociety.org), led by Dr. Rick Kreider at Baylor University, did show that daily doses of the product (12 grams per day for eight weeks in resistance-trained males) led to significant increases in maximal single repetition bench press and stationary cycling sprint performance, but proved no better than placebo in relation to muscle or fat mass changes, treadmill endurance, leg extension performance or self-reported measures of sexual function or muscle hardness. It will be interesting to see how these results, contrasted with the backdrop of a legacy of far more aggressive on- and off label claims, will be portrayed by GNC, its publications and in other publications.
Competitive Insulation: Hollow Trophies in the Attic?
The allure of issued patents on compositions, and to a lesser extent, methods of use, for nutraceutical products has enjoyed incremental magnification over the past several years. Seminal examples of patents germane to sports nutrition products and with teeth, i.e. vigilant enforcement campaigns, include HMB (MTI) and chromium picolinate (Nutrition 21, Purchase, NY; prior to the composition of matter patent expiring). Hundreds of patents (issued and pending) claim compositions intended to function as a sports nutrition product. On- and off-label claims of "patented" or "patent pending" continue to become more and more hollow as a fewer and fewer percentage of issued patents are enforced.
Two examples of long infringed patents are both assigned to Muscletech and relating to food supplements containing creatine and a form of lipoic acid or carbohydrates (or any composition that can increase insulin concentrations in the blood, e.g. protein), both as embodied in Muscletech's Cell-Tech product. Numerous companies have been marketing apparently infringing compositions for several years. The creatine-carbohydrate/insulin boosting patent was acquired by Muscletech from the University of Nottingham, its lead inventor being Dr. Paul Greenhaff.
Competitive insulation can be achieved via other means. Case in point is Gatorade and its "35 years of research." The category-creating position, nearly global distribution of the product, and the strong unaided consumer recall of the brand are pivotal elements in its domination of the energy drinks category. This is contrasted to Red Bull, which enjoys a suite of several published clinical trials describing its ergogenic and alertness-enhancing effects, albeit without the ideal control comparisons. The sponsorship activities of Red Bull in motorsports, especially the largest viewed sport on a global scale-Formula 1-helped catapult it past the $1 billion sales mark in 2003, undoubtedly assisted by its popularity in the nocturnal "hydration sportspersons" that frequent night clubs and bars.
A new contender in the energy drinks category hails from Pacific Health Labs, Matawan, NJ. Accelerade, an RTD beverage or ready-to-mix (RTM) powder (both combine carbohydrates + protein) initially positioned for the endurance activity individual, has attempted to erode the prestige and perception of Gatorade (a protein-free beverage/RTM) by sponsoring head-to-head comparison studies at high profile university laboratories and yielding superior results. Endurox R4 is an RTM that leverages a 4:1 ratio of carbohydrates to protein, with some evidence showing increased muscle glycogen repletion following intensive exercise. These products (with a patent and patents pending) were launched with a mass market focus and may build a more infectious viral marketing network and sales velocity if they were repositioned for the core enthusiast. GNC ex-CEO Greg Horn is on the board of the company and may be able to redirect the ship as he did with finesse and aplomb while at the helm of GNC. What will be of additional interest is whether competitor companies will engage in duplicative distraction and elicit patent infringement suits or even claim patent invalidity because of prior art.
It is important to note that U.S. patent law is more lax in its requirement of "data" proving the claims in a patent application. Indeed, in the majority of nutraceutical-centric patents issued NO proof of concept data (in animals or humans) is provided, let alone placebo-controlled, randomized trials. In the U.S. patent system, having a patent on a nutraceutical composition is tantamount to owning a plot of land with no access to water or utilities-it has very little value until its "utility" and "viability" are confirmed despite one still being able to claim they are "land rich."
For Whom Do the Bells Toll?
The sports nutrition market landscape is convoluted, heavily fragmented, and dotted with an increasing number of threats to those that stray outside of the operating boundaries. Product- or ingredient-specific clinical science still marks an infinitesimally small number, while claims and stories by raconteurs and "experts" alike abound. The drive for clinical research substantiation of products and ingredients is indeed compelling more companies to make the investment and take the risk (as they do with advertising and marketing campaigns), but also is fostering a graveyard of undisclosed studies with "non-positive" results. Among the companies that invest in real science and IP (intellectual property), the challenge is to exploit the investment and maintain leader market share, even a category monopoly.
The remainder of this decade will likely unfold with more regulatory enforcement, greater political heat and a thicker cloth being woven that attempts to (spuriously) link illicit ergogenic and anabolic synthetic agents and OTC dietary supplements and even some foods and beverages. With the physiques of certain sportswomen and sportsmen being exalted to an extent that parallels their respective physical talents, questions about "drug-free" will carry on as the Anti-Doping Agency continues its push for aggressive testing and action.
Several years ago we successfully defended a prominent professional football player who had failed a drug test, his urine reflecting use of the anabolic steroid nandrolone, or (as we asserted) ingestion of an OTC dietary supplement steroid that was not on the NFL banned substances list. Today, claiming a dietary supplement caused a failed drug test rarely is a viable defense. What remains enigmatic is why an athlete such as a baseball player can be instantly suspended for using cork in a bat or Vaseline on a baseball but still continue to play if caught using true anabolic steroids or growth hormone. To achieve the rarefied status of being safe and effective the sports nutrition industry needs to put its money where its muscles are and use a strong evidence base to combat the relentless skepticism that it invites. NW
About the author:
Mr. Almada is the co-founder of Experimental and Applied Sciences (EAS), the president and chief scientific officer of IMAGINutrition, Inc., Laguna Niguel, CA, a founding partner in Mercura, LLC (www.mercuraip.com), and is a regular columnist ("Proprietary Perspectives") for Nutraceuticals World. He can be reached at 949-363-5858; Fax: 949-363-1758; E-mail: anthony@imaginutrition.com; Website: www.imaginutrition.com.
Disclosure: Mr. Almada is on the editorial advisory board of Nutrition Business Journal, is a consultant to Nutrition 21, receives royalty payments from iSatori from the sales of Meta-CEL, a creatine/D-pinitol product, and still takes creatine (as Meta-CEL) on a daily basis.
