PROTANDIM: This product is made of 225 mg milk thistle extract, 75 mg turmeric extract, 150 mg ashwagandha powder, 150 mg bacopa, and 75 mg green tea extract. It costs $40 if purchased by monthly automatic shipping, otherwise $50 from Lifevantage.com or Protandim.com, or an independent distributor. This product began to be sold in 1993 in retail stores like GNC. The company LifeVantage changed to a network marketing model in 2009 because the product's benefits could be explained better by distributors, and sales skyrocketed. The company states: "Protandim activates the body's natural ability to reduce age-related symptoms on the cellular level. Protandim reduces oxidative stress in humans by an average of 40 percent in 30 days. It activates Nrf2 to communicate with your DNA to deliver a biochemical wake-up call to your genes. Certain foods, especially fruits and vegetables, contain antioxidants. But Protandim will boost your body’s production of antioxidants more effectively by activating the protein Nrf2, telling cells to turn on a network of antioxidant enzymes and protective genes." Dozens of leading institutions are studying Protandim and how it helps people with diabetes, hypertension, skin cancer, bypass grafts, etc. Studies show a 30% increase in Superoxide Dismutase (SOD), 54% increase in Catalase (CAT), and 300% increase in Glutathione, with regulation of over 3000 genes. It has been featured in many popular media sources (Dr. Phil, Dr. Oz, abc primetime, PBS Healing Quest, NBC Today, etc). It is patented. See Lifevantage.com.
ASEA: This product is made of a scientifically formulated liquid containing a special saline water infused with "redox signaling molecules" that supposedly goes quickly to the body's cells to cause homeostasis. It costs $75. for a two bottle pack (32 ounce bottles). Users drink 2 or more ounces per day, and say it tastes like salt water. It can be purchased from asea.net or from an independent distributor. This company began as a network marketing company by two retired executives. The doctors who studied and developed this product were around a table one day when some representatives from a pharmaceutical company suddenly interrupted their meeting and offered to buy the patent and rights to the product for one billion dollars. The doctors said they would discuss the offer while the representatives waited in the lobby. Each doctor gave his opinion. Some of the doctors had studied this formula their whole lives and were not willing to sell out, and all unanimously declined the offer and kept the rights. The company states: "ASEA (also called ASEA water by some people) is trillions of stable, perfectly balanced Redox Signaling Molecules suspended in a pristine saline solution—the same molecules that exist in the cells of the human body. Redox Signaling is a function that is central to all life on the planet. Redox Signaling molecules are created within every cell of the body and are vital to the immune system and to cellular healing mechanisms. They are so essential to life that without them, you would die within seconds. A proper supply of Redox Signaling molecules enables cellular healing: damaged, dysfunctional cells fading away and healthy, vibrant cells taking over. Redox Signaling molecules are vital for the health of your cells; that’s why your body makes its own supply. But after the age of 12, our cells make fewer and fewer of these molecules. ASEA is the world’s only source for replenishing Redox Signaling molecules. ASEA is the first and only stable, perfectly balanced mixture of these Redox Signaling reactive molecules that exists outside of living cells, and can be used to help maintain proper balance inside the body to support the immune system and healing process." Although not advertised as a Nrf2 activator, the research clearly states that it does activate Nrf2, and increases glutathione production 500%. There have been numerous scientific studies on this product. See asea.net.
Ultimate Protector. This product is made from many natural products and foods. It contains USP-grade non-GMO Buffered Vitamin C, AnthoComplete™ (high-ORAC powder: 3000 units/g from Wild Blueberry, Wild Bilberry, Acai, Black Currant Extract, Sweet Cherry, Raspberry, Elderberry, Blackberry, Aronia, Black Soybean Hull Extract, and Blue Corn), CoffeeBerry®Forte® (high-ORAC powder: 6,000 units/g from Coffee Berry), Curcumin (standardized extract with 95% curcuminoids), Trans-Resveratrol (98% from Giant Knotweed), VitaBerry®Plus® (high-ORAC powder: 12,000 units/g from freeze-dried Grape Seed, Wild Blueberry, Wild Bilberry, Cranberry, Tart Cherry, Prune, Raspberry Seed, Strawberry, Trans-Resveratrol, and Quercetin), VitaVeggie® (high-ORAC powder: 6,000 units/g from Broccoli, Broccoli Sprouts, Tomato, Kale, Carrot, Brussels Sprouts, Onion and Spinach), and Bioperine® (a patented black pepper extract that enhances absorption of all ingredients). It sells online only, for $39.95. The company states: “ULTIMATE PROTECTOR™ is a next generation cell protection formula that simultaneously meets the needs for high levels of Vitamin C, full spectrum of high ORAC [oxygen radical absorbance capacity] antioxidants, and protective enzyme activators (Nrf2 activators) in a single product. This potent combination of characteristics distinguishes the formula because no other single product available today offers such complete protection. ULTIMATE PROTECTOR is a quantum leap forward in providing total antioxidant protection from all types of free-radicals! At 486,000 ORAC 5 units per day, this is the most potent antioxidant formula you'll find, anywhere. ULTIMATE PROTECTOR is hands down the most effective cell protection, antioxidant formula ever formulated. Not only does it provide extraordinary protection for cells, but because it so effectively quenches free radical activity, it supports the health of all tissues and organ systems in the body. And, even as it keeps the body healthy by reducing harmful effects of free radicals, it also prevents, mitigates, and reduces adverse free-radical effects due to conditions of poor health that create additional oxidative stress. The formula thereby protects you both from oxidative damage that contributes to poor health and from oxidative damage resulting from conditions of poor health.” It has several patents, and is described quite extensively on its website http://www.integratedhealth.com/hpdspec/ultimate-protector.html.
Cellgevity. This product is made from RiboCeine, Alpha Lipoic Acid, Broccoli Seed, Turmeric, Resveratrol, Grape Seed, Quercetin, Milk Thistle, Vitamin C, Selenomethionine, Cordyceps, Black Pepper, and Aloe. It is sold online or by direct distributing "associates" for $65 loyalty price, $79 wholesale price, or $97 retail price. The company states: “Every cell in your body is under a never-ending attack from free radicals and chemical toxins. Glutathione is the cell's primary protector and detoxifier. It is your body's natural safeguard against accelerated aging. Unfortunately, your cells just can't make enough of it. Cellgevity™ provides your cells with patented nutrients that have been clinically shown to raise intercellular glutathione levels more effectively than any other supplement. Cellgevity features the patented nutrient RiboCeine™ combined with 12 synergistic ingredients scientifically selected to support and enhance the natural functions of glutathione.”
Learn more on their website http://max.com/products/max/full/us/en/cellgevity
Nrf-2 Optimizer. This product is made from Sulforaphane, Black Pepper, Turmeric, Green Tea, Pterostilbene, and Bacopa. It is only available online, for $45.99. The company states: “Our specially formulated NRF2 Optimizer is an antioxidant enforcing supplement that is intended to upregulate our body’s natural antioxidant defense mechanisms for detoxification, reduction of oxidative stress and also downregulates mechanisms that relate to inflammation and overall disease progression. Nuley’s 100% naturally-sourced and vegetarian ingredients help to improve our body’s antioxidant support, Anti inflammatory support and detoxification processes. Although we ingest antioxidants in the food that we eat every day, it is widely known that we cannot eat enough antioxidants to compensate for the volume of free radicals that attack our bodies. Nuley’s modern NRF2 antioxidant amplification supplement represents the pinnacle of knowledge regarding Anti aging nutrition, and increases your body’s natural antioxidant process over 1000%.” Their website is http://www.nuley.com/.
Nrf2 Advantage. This product is made out of the exact ingredients in the same amounts as Nrf-2 Activator (Glucoraphanin, Turmeric, Green Tea, trans-Pterostilbene, and Black Pepper), probably because the holder of the patent is allowing two different companies to sell it under different brand names. However, this one is more expensive, at $76.95. The company even makes the same statement: "Nrf2 Advantage, developed by Dr. David Perlmutter, is an exclusive formula designed to activate the Nrf2 genetic pathway. This pathway regulates the production of important molecules that impart antioxidant activity, such as glutathione and superoxide dismutase (SOD). It also regulates the production of detoxification enzymes, including glutathione S-transferase, and downregulates signaling factors such as NF-ϰB for a healthy response to inflammation. Each ingredient in this formula is backed by extensive research in peer-reviewed journals." It is available online. See the website drperlmutter.com.
AI-3. This product is a drug, available for $169 for 10 mg. The company describes its biological activity as: “Antioxidant response element (ARE) activator; disrupts Nrf2/Keap1 and Keap1/Cul3 interactions and stabilizes Nrf2. Activates ARE in an Nrf2 and PI 3-kinase dependent manner. Induces cytoprotective gene expression in vitro and in vivo.” Reference: Wang et al (2013) In vitro and in vivo characterization of a tunable dual-reactivity probe of the Nrf2-ARE pathway. ACS Chem.Biol. 8 1764. PMID: 23773140. It is available at tocris.com and RNDsystems.com.
Andrographalide. This product is a drug, available for $89 for 50 mg. The company describes its biological activity as: Inhibitor of NF-κB signaling; also attenuates concanavaline-induced IFNγ production in murine T cells (IC50 = 1.7 μM). Blocks androgen receptor (AR) expression in AR-expressing C4-2 cells. Activates Nrf2 in BEAS-2B cells in response to cigarette smoke extract. References: Burgos et al (2005) Andrographolide inhibits IFN-gamma and IL-2 cytokine production and protects against cell apoptosis. Planta.Med. 71 429. PMID: 15931581. Liu et al (2011) Andrographolide targets androgen receptor pathway in castration-resistant prostate cancer. Genes Cancer. 2 151. PMID: 21779488. Guan et al (2012) Andrographolide protects against cigarette smoke-induced oxidative lung injury via augmentation of Nrf2 activity. Br.J.Pharmacol. [Epub ahead of print]. PMID: 23146110. It is available at tocris.com and RNDsystems.com.
Curcumin. This product is sold as a drug, available for $59 for 50 mg. The company describes its biological activity as: Antitumor, anti-inflammatory and antioxidant agent. Downregulates expression of reactive-oxygen-generating enzymes (cyclooxygenase, lipoxygenase, iNOS), TNFα, IL-1, IL-6, PKC, EGFR, NF-κB, IκB kinase and more. Upregulates expression of PPARγ, p53, Nrf2. Also displays antimicrobial, antidiabetic neuro- and cardioprotective properties in vivo. References: Cole et al (2007) Neuroprotective effects of curcumin. Adv.Exp.Med.Biol. 595 197. PMID: 17569212. Kuttan et al (2007) Antitumour, anti-invasion, and antimetastatic effects of curcumin. Adv.Exp.Med.Biol. 595 173. PMID: 17569210. Lin (2007) Molecular targets of curcumin. Adv.Exp.Med.Biol. 595 227. PMID: 17569214. Miriyala et al (2007) Cardioprotective effects of curcumin. Adv.Exp.Med.Biol. 595 359. PMID: 17569220. Aggarwal and Sung (2009) Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets. TiPS 30 85. PMID: 19110321. It is available at tocris.com and RNDsystems.com.
Nrf2 Activator IV. This product is a drug, sold for $178 for 10 mg. The company description is: A cell-permeable vinylsulfone that acts as a more potent Nrf-2 activator than the chalcones in stimulating HO-1 expression in murine microglial BV-2 cultures. Shown to induce overall Nrf2 cellular accumulation & nuclear translocation in murine dopaminergic CATH.a cultures, presumably by freeing Nrf2 from its negative regulator keap1, with concomitant upregulation of Nrf2-regulated antioxidant enzymes expression, effectively protecting CATH.a against BH4 in vitro and preventing MPTP- induced motor dysfunctions and neurodegeneration in a murine PD model in vivo. It is available at the company’s website: embmillipore.com.
Dimethyl Fumarate. This product is a drug, available for $40 for 50 mg. The company describes its biological activity as: “Nuclear factor (erythroid-derived)-like 2 (Nrf2) pathway activator; induces upregulation of antioxidant gene expression. Displays cytoprotective effects in human spinal cord astrocytes, oligodendrocyte precursor cells and hippocampal neurons following hydrogen peroxide challenge. Exerts neuroprotective effects in vivo in experimental autoimmune encephalomyelitis. Primary metabolite (MMF, Cat. No. 4511) available.” References: Linker et al (2011) Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the Nrf2 antioxidant pathway. Brain 134 678. PMID: 21354971.; Scannevin et al (2012) Fumarates promote cytoprotection of central nervous system cells against oxidative stress via the nuclear factor (erythroid-derived)-like 2 pathway. J.Pharmacol.Exp.Ther. 341 274. PMID: 22267202. It is available at tocris.com and RNDsystems.com.
Monomethyl Fumarate. This product is a drug, available for $45 for 50 mg. The company describes its biological activity as: Nuclear factor (erythroid-derived-2)-like 2 (Nrf2) pathway activator. Also exhibits agonist activity at GPR109A. Primary metabolite of DMF (Cat. No. 4512). References: Rao & Mishra (1998) Antihepatotoxic activity of monomethyl fumarate isolated from Fumaria indica. J.Ethnopharmacol. 60 207. PMID: 9613834. Tang et al (2008) The psoriasis durg monomethylfumarate is a potent nicotinic receptor agonist. Biochem.Biophys.Res.Commun. 375 562. PMID: 18722346. Hanson et al (2010) Nicotinic acid- and monomethyl fumarate-induced flushing involves GPR109A expressed by keratinocytes and COX-2-dependent prostanoid formation in mice. J.Clin.Invest. 120 2910. PMID: 20664170. Scannevin et al (2012) Fumarates promote cytoprotection of central nervous system cells against oxidative stress via the nuclear factor (erythroid-derived 2)-like 2 pathway. J.Pharmacol.Exp.Ther. 341 274. PMID: 22267202. It is available at tocris.com and RNDsystems.com.
Oltipraz. This product is a drug, available for $315 for 50 mg. The company describes its biological activity as: Nrf2 activator; activates Nrf, which binds to antioxidant response elements (AREs) and induces Phase-I and -II drug-metabolizing enzymes including CYP2B and NQO1. Also increases mRNA levels of multiple hepatic xenobiotic transporters. Elevates expression of genes encoding anti-oxidant and multidrug resistance-associated proteins. Displays chemopreventive activity. References: Maher et al (2007) Oxidative and electrophilic stress induces multidrug resistance-associated protein transporters via the nuclear factor-E2-related factor-2 transcriptional pathway. Hepatology 46 1597. PMID: 17668877. Manandhar et al (2007) Induction of Nrf2-regulated genes by 3H-1, 2-dithiole-3-thione through the ERK signaling pathway in murine keratinocytes. Eur J Pharmacol. 577 17. PMID: 17854798. Merrell et al (2008) Induction of drug metabolism enzymes and transporters by oltipraz in rats. J.Biochem.Mol.Toxicol. 22 128. PMID: 18418891. It is available at tocris.com and RNDsystems.com.
TAT 14. This product is a drug, available for $155 for 1 mg. The company describes its biological activity as: Nrf2 activator; inhibits Nrf2/Keap1 interaction. Induces upregulation of Nrf2 pathway downstream gene expression including heme-oxygenase 1. Suppresses LPS-induced TNF-α expression in THP-1 cells. Reference: Steel et al (2012) Anti-inflammatory effect of a cell-penetrating peptide targeting the Nrf2/Keap1 interaction. ACS Med.Chem.Lett. 3 407. PMID: 22582137. It is available at tocris.com and RNDsystems.com.
OTHER INFO TO COMPARE:
DRUGS are intended to to diagnose, treat, cure, mitigate, and prevent diseases, and are regulated by the FDA. Most drugs are chemically created in a lab, so they are not natural and usually have undesirable side effects.
DIETARY SUPPLEMENTS are usually vitamins and herbs that are promoted as helping with one's health. They are leaves, stems, or roots of natural plants that grow in various places of the world, and usually have no side effects (unless you have a rare allergy to them). However, although they may have been used as medicinal herbs and treatment for various diseases over the centuries, the FDA does not study herbal remedies, and currently restricts distributors of such products from making such claims as "treatment," since that term is reserved for rigorously studied and approved drugs. So even though some Nrf2 activators are herbs and do the exact same thing as Nrf2 activating drugs, distributors need to be careful not to claim that the herbs are "intended" to cure. Rather, the stated "intention" should be to help the body do its own job better - the body fights the disease (the herb doesn't fight the disease).
EFFECTIVENESS of any herb or drug depends on several factors, including the genetics of the individual and their size, weight, diet, physical activity, exposure to environmental toxins, tobacco or alcohol use, simultaneous use of other medications, etc. Generally healthy or younger people may not feel any benefit of Nrf2 activators at all, unless by paying close attention they notice a quicker recovery time between workouts, less being "sore" after strenuous exercise, better sleep, or less feeling tired during the day. Blood tests will prove Nrf2 activators are working though - even though you can't feel it. Just like a diabetic cannot "feel" what their blood-sugar count is, and you cannot "feel" what your cholesterol level is, you also cannot "feel" what your T-Bar level is (which measures your body's response to oxidative stress). Contrastingly, people with multiple diseases and physical problems may strongly notice a very rapid recovery from their multiple symptoms, and their doctor may shocked at their strikingly quick improvement, and they may be allowed to wean off their dozens of medications and go down to only a few because of their good health.
GLUTATHIONE is a body-generated antioxidant that prevents damage to cell components caused by free radicals. It neutralizes free radicals, maintains vitamin C and E in active forms, has a role in DNA synthesis and repair, synthesizes proteins, activates enzymes, and transports amino acids. Every system in the body can be affected by Glutathione, esp. the immune system, nervous system, gastrointestinal system, and lungs. Low glutathione levels are commonly observed in patients with cancer, HIV/AIDS, sepsis, trauma, burns, athletic overtraining, and autism. Promising studies are currently underway showing that Glutathione makes kids with autism more social. Nrf2 "tells" the DNA to make it.
RETAIL MARKETING is the usual way that people are used to. Companies make a product, then sell it to a wholesaler, who sell it to a retailer, who put it on the shelves at a store. Customers simply come in to the store and buy what they want. They can easily see all the other products and different brands lined up on the shelf, and can compare features and prices and choose what they want. Protandim used to be sold in stores like GNC, but had few sales because it was placed in the aisle with several Antioxidants that cost $12, while Protandim cost $40, and neither the label nor the store clerks could explain why there was such a big price difference. People generally are not aware of the huge benefits of Nrf2 activators because there are few if any of them on the shelves in retail stores today - they are sold mostly on the internet or via network marketing.
INTERNET MARKETING is the new way that people are buying products. Companies make a product and put it up for sale directly on their website. People can search for a product they want on the internet, and keep searching different websites until they find a product they want that will meet their wants or needs. Vitamins, minerals, and supplements tend to do very well with this type of marketing because they are lightweight and easily shipped, and don't require refrigeration or bubble-wrap padding. Most of the Nrf2 activators are sold on company websites.
NETWORK MARKETING is a type of direct sales, in which a person becomes an independent distributor of a company, then has authorization to advertise their product in personal conversations with friends, relatives, co-workers or anyone else they meet. This has been very beneficial to companies that make products that need more explaining than what the product label gives. On a small pill-sized bottle, it is difficult to tell all the benefits of the product when there is barely room to print the brand name, the ingredients, and the FDA-mandated statements. When LifeVantage began selling Protandim using a Network Marketing model, their sales increased dramatically because distributors were able to explain what the product did. With this type of marketing, Instead of paying the 50% markup from wholesale to retail, the companies pay the money directly to their "independent distributors" who do the work of face-to-face advertising and explaining. Distributors often try to recruit others to sell the product too, because the more people they get selling in their "network" that they build, the more products are sold and the more bonuses they can earn. Many customers who have positive experiences with Nrf2 products end up becoming distributors because they are excited about telling their "story" and can get paid when people buy from them or others in their "downline" organization. This is why there seem to be abundant product testimonials from network marketing companies (Protandim, Cellgevity, ASEA, Vivix), and fewer reviews from internet-based or drug companies. The products work regardless of what company they are bought from - it's just that some have a bigger incentive to tell of their experiences.