The Science behind Livital®
Liver Detoxification – a three-phase process
The liver is a remarkable organ that plays a crucial role in our health. A healthy liver can filter all the blood in circulation several times per day removing bacteria and toxic substances including both environmental toxins such as drugs and pollutants as well as compounds created within the body such as metabolic end products. The liver may contain half a liter of blood at any given time.
There are three phases of liver detoxification. Phase 1 detoxification uses between 50 and 100 different enzymes (collectively known as the Cytochrome P450 system) to initially modify toxins. This is usually done by oxidation, reduction, or hydrolysis—essentially adding or removing an oxygen or OH group from the chemical. This initial modification quickly reduces the toxicity of most compounds to some degree and prepares them for Phase 2. Phase 1 detoxification typically makes toxins less harmful, but in some cases it creates metabolites that are more active (toxic) than the original compound. Some Phase 1 metabolites are even carcinogenic.
Phase 2 is the most crucial phase in liver detoxification and it is the final phase for most toxins within the body. In Phase 2 detoxification, the liver further processes the products of Phase 1 in a process called conjugation. Conjugation binds the toxin to another molecule (methyl group, sulphur, glucorate, glycine, or glutathione), which makes them less toxic, and often too large to enter cells. Conjugation also makes the Phase 1 metabolites water-soluble so they can then be eliminated through urine or bile.
In order to conjugate the Phase 1 metabolites, the liver needs metabolic energy to fuel the reaction, the required enzymes to fuel the reactions and the specific building blocks of the conjugation reactions. For example, sulphation reactions require specific sulfotransferase enzymes to facilitate the reaction and bioavailable sulphur molecules (co-factors) to bind to the Phase 1 metabolite. Glycine conjugation requires aceyl co-enzymes and glycine as a co-factor. If the liver does not have enough energy or the specific enzymes or co-factors necessary to conjugate the metabolites created in Phase 1, then there is a bottleneck and Phase 2 detoxification does not occur. When this happens, the Phase 1 metabolites continue to circulate in the body until the bottleneck is resolved. Since Phase 1 detoxification continues to occur, these metabolites continue accumulate in the blood.
In Phase 3 detoxification, some Phase 2 metabolites go through an additional chemical step before being excreted from the body. For example, glutathione conjugates are converted to acetyl-cysteine conjugates. Only some toxins require Phase 3 detoxification.
Phase 2 detoxification is the critical step in liver detoxification. It requires energy, specific co-factors such as sulphur compounds, and specific liver enzymes. When all of these elements are not present in ample amounts, partially metabolized toxins from Phase 1 accumulate. Therefore, it is crucial to provide these important building blocks of Phase 2 detoxification. There is ample evidence that increasing the amount of Phase 2 enzymes to induce more detoxification is a major strategy in protecting against malignant cancers.
BroccoRaphanin® Broccoli seed extract
Brassicas such have broccoli and cabbage have long been suspected as playing a role in protection from cancer and other diseases.[2,3] These vegetables contain not only sulphur compounds but high levels of compounds that induce Phase 2 liver enzymes.
BroccoRaphanin® is the patented form of sulforaphane glucosinolate (SGS), a sulphur compound found in many vegetables in the Brassica family such as broccoli and cabbage. SGS is found in the highest concentration in the sprouted seeds of brocolli (Brassica oleracea italica). SGS has indirect, long-acting antioxidant properties,[5,6,7] is a broad spectrum antimicrobial against both gram-positive and –negative bacteria. SGS also exhibits anticancer properties. GSG has been shown to be safe even in high (therapeutic) doses.
SGS is particularly notable for liver detoxification because it is also the most potent inducer of Phase 2 detoxification enzymes found in nature., SGS has been shown both in cultured cells and animals to be a major inducer of anti-carcinogenic Phase 2 liver enzymes.
A single-blind, randomized, placebo-controlled study of glucosinolate from broccoli sprouts was performed on 200 residents of Qidong, China. Due to high levels of hepatitis virus and environmental toxins such as food contaminated with aflatoxins, the residents of Qidong’s He Zuo township are at high risk for hepatocellular carcinoma. In the study, on half of the subjects were supplemented with hot water extract of broccoli sprouts containing Glucoraphanin a precursor of SGS. The group that received brocolli sprout extract showed a significant decrease in a biomarker for DNA damage from aflatoxin and this reduction in the biomarker increased as the broccoli sprout extract levels increased. The reduction in this biomarker signaled that detoxification was occurring in dose-dependent way from the brocolli sprout extract consumption.
SGS has been shown to convert to the Phase 2 liver enzymes quinone reductase (QR) and glutatione S-transferase (GST) in rodents. GST is the essential enzyme in all glutathione conjugation within the liver. It is a very powerful antioxidant that is depleted by detoxifying Phase 1 metabolites. GST primarily detoxifies toxins from outside the body (xenobiotics) including drugs, pesticides, herbicides, and carcinogens.
N-Acetylecysteine (also known as N-Acetyl-L-Cysteine or NAC) is a compound created by adding an acetyl group to the nitrogen atom to a cysteine amino acid. In the liver, NAC replenishes glutathione so that it can continue to be used in conjugation reactions.
Doctors use NAC as the primary treatment for acetaminophen (Tylenol) overdose. Overdosing on acetaminophen can cause fatal irrevesible liver damage and is the most frequent cause of acute liver failure in the Western world. One of the Phase 1 metabolites of acetaminophen is N-acetyl-P-benzoquinone imine (NAPQI). NAPQI is conjugated by glutathione but in the case of an overdose, NAPQI overwhelms the liver’s supply of glutathione. The build up of toxic NAPQI damages the liver and may ultimately be fatal. To treat this, doctors administer NAC which replenishes glutathione so that the liver can continue to conjugate and eliminate NAPQI.
Acetaminophen overdose is an extreme example of the dangers of overwhelming the liver’s supply of glutathione. However, other Phase 1 metabolites may also overtax the body’s supply of glutathione. Although the results of this depletion are not as accute, because of a lack of glutathione, Phase 2 detoxification of compounds requiring glutathione conjugation will bottleneck if the liver lacks the proper amount of this essential co-factor. Livital includes NAC in its formulation to ensure that the liver has both the proper amount of the glutathione co-factor in addition to the enzyme glutathione S-transferase (GST) which is provided by the BroccoRaphanin® broccoli seed extract. Only with both of these components is the liver is able to freely perform this mechanism of Phase 2 detoxification.
Glucuronidation is one of the mechanisms of Phase 2 liver detoxification often associated with conjugating xenobiotics with glycosidic bonds such as pollutants, drugs, and estrogenic and androgenic compounds. The role in removing estrogen and xenoestrogenic compounds is of particular interest here.
Xenoestrogens occur in nature (e.g. soy isoflavones) but have become far more prolific in the environment over the last 70 years as a result of industrial pollutants. These compounds have been implicated in numerous medical conditions from sexual function and reproductive problems for men[18,19] to breast cancer in women[20,21] to precocious puberty in children to name just a few. Common xenoestrogens include well known pollutants and endocrine disruptors BPA (Bisphenol A), DDT, Dioxin, Parabens, PCBs, and Phthalates.
The body removes excess estrogen and xenoestrogenic compounds via the Phase 2 liver detoxification mechanism of glucuronidation by binding these compounds to glucuronic acid and then excreting them in bile or urine. However, this process can be disrupted by the enzyme beta-glucuronidase which seperates these components again so that the estrogenic compounds are free to move through the body again.
Beta-glucuronidase is present in the intestines where it breaks down some polysaccharides for absoption. Calcium D-Glucarate inhibits beta-glucuronidase so that estrogens or any other toxins conjugated through glucuronidation are not broken down and reabsorbed by the body.
In clinical trials, tissues that are sensitive to excess hormones –such as breast, liver, and lung—have been shown to respond favorably to Calcium D-Glucarate.[23,24,25] Calcium D-Glucarate has been shown to be a protective agent in breast cancer. In addition to estrogen and estrogenic compounds, Calcium D-Glucarate helps promote excretion of other hormone metabolites as well as cellular toxins and steroids.
Published human studies on Calcium D-Glucarate and breast cancer are few but, due to encouraging results of animal studies, the National Cancer Institute has initiated a Phase I trial in high-risk patients for breast cancer at Memorial Sloan Kettering Cancer Center.
Like sulfuraphrane, indole-3-Carbinol (I3C) is a component of brassicas (broccoli, cauliflower, etc.) that is produced by the breakdown of a glucosinolate. Current research suggests that I3C may have anticarcinogenic and antioxidant functions. Most research to date has been in vitro and animal studies. Results have shown decreases in the amount of aflatoxin-DNA binding biomarkers related to the dose of I3C. This has been taken as anti-cancer initiating activity.
I3C induces the arrest of the G1 phase of cell growth for human reproductive cancer cells. The G1 phase is the earliest and typically the longest phase of cell growth, during which these cells synthesize the enzymes they will require to procede to the S phase in which they can begin replicating their DNA. Arresting cell growth during the G1 phase is potentially relevant in preventing and treating cancers.
I3C naturally occurs in brassicas along with the compounds that create sulfraphrane. These may work together as co-factors in detoxification and cancer prevention. In rodent studies, I3C has been shown to induce enhanced levels of GST in the liver and other organs. Livital contains a therapeutic dose of approximately 1,000 times the I3C that a person could normally consume in a normal diet.
Turmeric has a long history as both a culinary spice and a medicinal herbal. Turmeric (Curcurma longa) is a rhizome that resembles ginger. Dried and ground to a powder, it contributes the flavor and characteristic yellow color to curry dishes. The active component, curcumin has been shown to treat inflammation within the body.
There have been over 3,000 preclinical investigations into curcumin’s actions making it one of the most thoroughly investigated compounds available. This research reveals curcumin’s role as a “master switch” for inflammatory compounds within the body because it acts at the body’s gene-expression level to turn off expression of pro-inflammatory enzymes.
In addition to anti-inflammatory actions, Curcumin has been shown to have anticancer, antioxidant actions and liver-protective actions. In one human study of 60 subjects in South Korea, (randomized) subjects received either 3g per day of fermented turmeric powder or a placebo. All subjects were 20 years of age or older and had been diagnosed with mild to moderate levels of elevated alanine aminotransferase (ALT), a biomarker of liver damage and/or disfunction. After 12 weeks of supplementation, the subjects who received turmeric showed significant reductions in both levels of ALT and gamma-glutamyltransferase (GGT) another biomarker for liver damage, indicating reduced liver damage and/or disfunction. The reduction of ALT and GGT persisted as long as the supplementation continued.
Numerous studies have shown curcumin’s ability to protect the liver against alcoholic liver disease, nonalcoholic fatty liver disease and drug-induced liver toxicity.[36,37] Curcumin can normalize antioxidant enzymes and nonenzyme antioxidant compounds including glutathione S-transferase (GST). Due to a variety of specific antioxidant and anti-inflammatory actions, curcumin has been shown to effectively mitigate nonalcoholic fatty liver disease.
One recent study of curcurmin in diabetic rats showed that curcumin supplementation actually helped liver tissues recover from damage from inflammation and accumulation of toxic lipids. In the 8-week trial on diabetic rats, those administered 200mb/kg of body weight were found to have recovered liver tissues and regained a normal pattern of liver micro-structures (veins, sinusoid, hepatocytes and portal triad) compared to the control group. Liver microvascular structure in the curcumin-treated group developed to regenerate and repair normal healthy characteristics.
While curcumin has great powers to protect the liver and reduce inflammation within the body, this is not easy to benefit from because curcumin has relatively low absorption levels. Curcumin is quickly denatured in the acidity of the digestive system. Further, curcumin has low solubility in water or fat. For these reasons, it is challenging to receive a therapeutic dose of curcumin from either dietary turmeric or standard curcumin supplements.
Meriva® is a patented form of curcumin which is bound to a phytosome molecule which makes it more than 20 times more absorbable within the body than curcumin alone. This allows the curcumin in Livital to better get into the body and contribute its liver-protecting effects.
Appendix A: References
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14. Munday, R. and Munday, CM Induction of Phase II Detoxification Enzymes in Rats by Plant-Derived Isothiocyanates: Comparison of Allyl Isothiocyanate with Sulforaphane and Related Compounds AgResearch, Ruakura Agricultural Centre, Private Bag 3123, Hamilton, New Zealand J. Agric. Food Chem., 2004, 52 (7), pp 1867–1871
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18. vom Saal FS, Cooke PS, Buchanan DL, Palanza P, Thayer KA, Nagel SC, Parmigiani S, Welshons WV (1998). “A physiologically based approach to the study of bisphenol A and other estrogenic chemicals on the size of reproductive organs, daily sperm production, and behavior”. Toxicol Ind Health 14 (1–2): 239–60.
19. Luconi M, Bonaccorsi L, Forti G, Baldi E (June 2001). “Effects of estrogenic compounds on human spermatozoa: evidence for interaction with a nongenomic receptor for estrogen on human sperm membrane”. Mol. Cell. Endocrinol. 178 (1–2): 39–45
20. Buterin T, Koch C, Naegeli H (August 2006). “Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells”. Carcinogenesis 27 (8): 1567–78.
21. Darbre PD, Aljarrah A, Miller WR, Coldham NG, Sauer MJ, Pope GS (2004). “Concentrations of parabens in human breast tumours”. J Appl Toxicol 24 (1): 5–13.
22. Aksglaede L, Juul A, Leffers H, Skakkebaek NE, Andersson AM (2006). “The sensitivity of the child to sex steroids: possible impact of exogenous estrogens”. Hum. Reprod. Update 12 (4): 341–9.
23. Walaszek Z, Hanausek-Walaszek M, Minton JP, Webb TE. Dietary glucarate as anti-promoter of 7,12-dimethylbenz[a]anthracene-induced mammary tumorigenesis. Carcinogenesis 1986 Sep;7(9):1463-6.
24. Walaszek, Z., et al. Dietary glucurate as anti-promoter of 7,12-dimethylbenz[a]anthracene-induced mammary tumorigenesis. Carcinogenesis 7(9): 1463-6.
25. Abou-Issa, H., et al. Relative efficacy of glucurate on the initiation and promotion phases of rat mammary carcinogenesis. Anticancer Res. 1995 May-Jun;15(3):805-10.
26. Heerdt AS, et al. Calcium glucarate as a chemopreventive agent in breast cancer. Isr J Med Sci 1995;31:101-5.
27. Dashwood, Rod H.; Arbogast, D.N.; Fong, A.T.; Pereira, C.; Hendricks, J.D.; Bailey, G.S. (1989). “Quantitative inter-relationships between aflatoxin B1 carcinogen dose, indole-3-carbinol anti-carcinogen dose, target organ DNA adduction and final tumor response”. Carcinogenesis 10 (1): 175–81.
28. Hsu, J; Dev, A; Wing, A; Brew, C; Bjeldanes, L; Firestone, G (2006). “Indole-3-carbinol mediated cell cycle arrest of LNCaP human prostate cancer cells requires the induced production of activated p53 tumor suppressor protein”. Biochemical Pharmacology 72 (12): 1714–23.
29. Esther M.M van Lieshouta, Gary H Posnerb, Benjamin T Woodardb, Wilbert H.M Peters. Effects of the sulforaphane analog compound 30, indole-3-carbinol, d-limonene or relafen on glutathione S-transferases and glutathione peroxidase of the rat digestive tract. Biochimica et Biophysica Acta (BBA) – General Subjects
Volume 1379, Issue 3, 2 March 1998, Pages 325–336
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Live with Purpose® for Liver Health
Your liver plays a critical role in health, detoxifying metabolic wastes, hormones and environmental toxins in a three-phase process. The human liver is capable of regenerating itself and liver health can be strongly influenced by nutrition and lifestyle choices.
The Live with Purpose® Program for liver health integrates the best in nutrition, dietary and lifestyle research to create a comprehensive program to get you on the right track quickly and easily. We have done the research into the simplest actions that give you the greatest results—the 80/20 rule for liver health. Here’s what we found:
Start with 5 Simple Steps
Get on the path to better liver health quickly and start feeling better faster by following these five simple steps.
LIVE WITH PURPOSE® PROGRAM FOR LIVER HEALTH
Supplement with Livital®.
Your liver plays a critical role in health, detoxifying metabolic wastes, hormones, and environmental toxins in a three-phase process. Phase 2 is a critical stage where toxins are neutralized, and this process relies on a combination of key micronutrients and enzymes.
Purpose Nutrition® Livital® is a patent-pending formulation of nutrients which work together in the body to nutritionally support efficient Phase 2 detoxification.* Patented calcium D-Glucarate and sulphoraphane glucosinolate from broccoli seeds have been the subject of numerous scientific studies for their role in detoxification and healthy liver function.* The BroccoRaphanin™ sulphoraphane glucosinolate in this product is refined from a proprietary, non-GMO broccoli seed, using a patent-pending process.
Drink a gallon of pure water each day.
Water is the most crucial element of life, and many of us don’t drink enough of it. Water makes us feel full, reduces cravings, keeps us hydrated, and helps flush metabolic wastes from the body.
All of the toxins that the liver detoxifies and tags for removal actually exit the body via the kidneys or intestines and water helps speed these elimination processes. Your liver must process almost a gallon of blood every two minutes. Proper hydration keeps the blood at optimum viscosity levels for the liver to process.
Drinking one gallon of water a day is just eight 16-ounce glasses, or one glass every two hours or so throughout the waking day. Keeping a favorite glass handy is a big help. Some of us have been mildly dehydrated for years, and simply drinking enough pure water can have a dramatic effect on improving the efficiency of our detoxification systems.
This quick start program lets you put the 80/20 rule to work for you basics, so you can start getting 80% of the benefit for just 20% of the effort. To go deeper, download the “Staying Well” chapter from Greg Horn’s latest book, Living Well [here].
Avoid everyday toxins.
Over 70,000 new chemicals have been introduced into our environment over just the past 100 years. Toxins are an inescapable part of our modern daily reality. Some of these toxins—especially estrogen mimics such as plasticizers and BPA found in everything from water bottles to cash register receipts—can alter our hormonal systems.
Avoid plastic water bottles and don’t handle cash register receipts without washing your hands thoroughly afterwards (BPA can absorb through the skin). Put aside the “-icides.” Anything that ends with –icide is meant to kill. Homocide is killing a person, herbicide is killing a plant, pesticide is killing a pest. Chemicals designed to kill cannot possibly be good for you. Put them aside and reduce your own exposure to everyday toxins.
Sleep is the great restorer for our bodies. Getting a consistent eight hours of sleep each night has an import place in any health improvement program. Two recent studies illustrate how important regular sleep is in particular for liver health.
In a study on animals, published in the December 2014 issue of Sleep, researchers found show a direct link where sleep deprivation causes oxidative DNA damage, particularly to the liver, followed by lungs and small intestines.1 Fortunately, the same study found that catching up on sleep can help reverse this damage and repair damaged DNA.
In a separate study on animals, researchers found that if sleep is interrupted from normal circadian rhythms, the liver cannot clear out the fat that it makes (as one of its many normal duties) during the day because two important markers are deactivated.2
Both of these studies have so far only been performed on animals—partly because it would possibly be impossible to perform them on humans—but this is a case where it seems pretty clear that what’s unhealthy for animals’ livers is also unhealthy for ours. The takeaway is this: for the liver to work correctly and avoid cellular damage, it’s necessary to get adequate sleep.
To get better sleep and maximize liver protection during this rest period:
- Make a sleep appointment for eight hours of sleep every night.
- Go to sleep and wake at the same time each day (even on weekends).
- Limit your light exposure for an hour before bed.
- Don’t eat or drink caffeine afternoon.
- Use your bed only for sleep (and one other thing).
Eat clean to live lean.
Eating “clean” means making thoughtful food and drink choices to maximize health. Simply put, food additives, preservatives, and pesticide and herbicide residue enter your body through your mouth—generally in the form of processed food. Your best bet is to minimize processed foods and especially sugars, fried foods and sweet drinks. Our 80/20 analysis yields food choices you can make to minimize load on your liver:
- Minimize processed foods, which contain preservatives, artificial colors, sweeteners and other chemicals that the liver has to process.
- Eliminate fried foods, which are high in fat and hard to process.
- Cut the white stuff, including sugar and refined flour which spike blood sugar.
- Eat low on the food chain, favoring vegetables and whole foods over meats and processed foods.
- Switch to organic foods, which is grown without using synthetic chemicals.
Liver Health Step-by-Step
Here’s an example of how you can easily incorporate the Live with Purpose® Healthy Liver Program into your life. Feel free to adjust times to your schedule, but keep an eight-hour period of uninterrupted sleep.
6:00 AM Wake up refreshed after a solid eight hours of restful, health-restoring sleep.
6:30 AM Choose an “eating clean” breakfast that leaves out sweeteners (sugar or artificial) and refined foods. Avoid white bread, breakfast cereals. (Many contain a lot of sugar and refined carbs), and fried foods like donuts. Unfortunately, fruit juices like OJ are mostly empty sugars without the fiber of real fruit. The good news is, if you’re craving orange juice, you can always eat an organic orange—they’re loaded with fiber and nutrients and actually taste a lot more orangey than sugary OJ.??Organic egg whites, with whole wheat toast and avocados can be a great day-starter that doesn’t come with a lot of toxins or processed, refined carbs. ??Finish breakfast with Livital® and a big glass of water to give your liver the supplements it needs for optimum health.
10:00 AM Time for a big glass of water. Add a small “eating clean” snack like a handful of organic almonds (but say no to granola bars or trail mix with their sugary stuff). Drinking water throughout the day—a sip or a glass at a time—helps keep you hydrated so your liver can work at full efficiency.
Noon Choose a delicious, clean lunch to keep you going through the day. A salad made from organic greens and lean protein would be a great choice. Have more water during the meal but steer clear of sodas (regular or diet) and other sugary or highly processed foods. Finish your meal with another Livital® capsule so your liver has a steady supply of health promoting ingredients.
3:00 PM Keep drinking your water through the afternoon. A fifteen-minute walk in the fresh air can help you recharge. Walking can even help you sleep more soundly at night.
7:00 PM Enjoy a great dinner that includes some fiber—fiber late in the day helps you feel full through the night so you sleep better. Organic whole-wheat pasta with tomato sauce and a serving or two of veggies would be a great option. Keep drinking the water and limit your alcohol intake to 1-2 drinks maximum. Remember, alcohol is a toxin that your liver must expend energy to process.
Have your last Livital® capsule of the day with, you guessed it, a big glass of water!
9:00 PM Start your bedtime routine an hour before you go to sleep (or 15 hours after you wake up, if you’d rather think about it that way). Lower the lights, turn off your digital devices (holding digital screens close to your face can interfere with the production of melatonin—our natural signal that it’s time to fall asleep) and downshift to a more relaxed state. Light housework or reading under a small incandescent lamp is a great way to settle in for sleep.
10:00 PM Time for bed. Make an appointment with yourself to be in bed with the lights out eight hours before you have to wake up the next morning. This will help you get the sleep that your liver—and really your whole body—needs to be healthy and feel great.
Live with Purpose®
Purpose®—we all have one. Pursuing it gives life meaning, making us more conscious of the choices we make in every dimension of our lives. These daily choices—how we nourish our bodies, minds, and intentions—determine our success at what really matters. Live with Purpose® programs are designed to give you maximum benefit most easily. Much more than just recommending a nutrition program, this integrated approach targeting better health for the whole person is our guiding philosophy behind each Live with Purpose® program. We believe that our choices should make yours easier— so you can pursue your purpose.
1. Nedergaard, Maiken et al. “Sleep Drives Metabolite Clearance from the Adult Brain.” Science 18 October 2013: Vol. 342 no. 6156 pp. 373-377 DOI: 10.1126/science.1241224