- 1 Section A
- 2 Reducing One’s toxic burden by supporting the body’s metabolic detoxification processes
- 3 Nrf2 activators
- 4 Sulphur coumpounds
- 5 Citrus
- 6 Calcium D-Glucarate
- 7 Chlorophyll
- 8 Probiotics
- 9 NAC
- 10 Milk Thistle
- 11 Phase III Transporters
- 12 Bile Flow
- 13 Section B
- 14 Avoiding toxin/toxicant exposure
- 15 Conclusion
- 16 General Recommendations
- 17 Key Synergistic Blends
- 18 Glutathione-Boosting Nutrients
- 19 Vitamin C
- 20 Exhibit A
- 21 Clinical Research on Increasing Glutathione Production
- 22 Reference and Precision Notes
- 23 Supporting Downloadable Reference sources
Both metabolic detoxification and purification rituals are fundamental and unifying tools in holistic medicine. In the same way that Traditional Chinese medicine starts with dispersing (and not tonifying) acupuncture point, in a similar way, holistic healing must first start with the “less is more” strategy, with the lowering of the body’s toxicity load, if only because we want to both clean-up endocrine, metabolic and immune signaling pathways and promote the healing crisis mechanism, the one Conventional medicine’s dignitaries choose not to teach.
“Chemicals that store in lipid-rich compartments have the potential for long-term disruption of metabolic and endocrine processes. Given the evidence that persistent organic pollutants (POPs) also alter systemic metabolic, endocrine, and immune system functions, it follows that elevated chemical concentrations in intra-abdominal fat may alter function, through local chemical signaling, of visceral organs.” (Source)
In this Page, I will thus examine how we can reduce one’s toxic burden endogenously (Section A), thereafter, I will looking into avoidance strategies so as to reduce or stop the toxicity influx (Section B) and afterwards, i will conclude with a few practical tips and detox recommendations
Reducing One’s toxic burden by supporting the body’s metabolic detoxification processes
Given the high number of detox enzymes and transport proteins involved in metabolic detoxification and its related pathways, holistic nutrition is a must. Quality macronutrient and micronutrient intake directly modulates (influences) phase I and II systems. Quality protein deficiency tends to decreases CYP metabolism, while high quality protein diets increase it. (1) The opposite effects are observed for carbohydrates, especially with the simple and refined carbs. In particular, efficient phase I reactions require sufficiency in several micronutrients, including, but not limited to vitamins A, B2 and B3, folate, C, E, iron, calcium, copper, zinc, magnesium, and selenium. All of these nutrients have been shown to decrease the activities of one or more phase I enzymes, or slow the transformation of specific drugs. (2) The diverse set of phase II enzymes require an equally diverse set of essential nutrients, especially B vitamins, as cofactors.
The reduced glutathione for GST conjugation depends on adequate dietary sulfur-containing amino acids (methionine or cysteine), vitamin B6 for the conversion of methionine to cysteine, as well vitamins B2 and B3 for the activity of glutathione reductase, which recycles oxidized glutathione. As for the methylation reactions, this pathway uses SAMe as a substrate; which, in turn, is synthesized through folate and vitamin B12-dependent enzymatic reactions. The conjugation reactions of the NAT’s and amino acid acyltransferases use the cofactor acetyl-coenzyme A (acetyl-CoA), which is synthesized from vitamin B5, using enzymes that themselves depend on multiple B vitamins.
Several phase II reactions require the energy molecule ATP in some fashion. For example, the chemical cofactors for the phase II methylation, sulfonation, glucuronidation, and glutathione conjugation reactions are all made using ATP; these ATP mediated reactions are magnesium-dependent. Flavonoids have been extensively studied in vitro and in animal models for their ability to lower the activity of CYPs, and increase phase II enzyme activities (except for SULTs, which they tend to inhibit. (3)
The inhibition of CYP activity by naringenin (the principle flavonoid in grapefruit) has been well documented in humans (4) hence the recommendation to avoid grapefruit when taking prescription drugs. Other flavonoids that have demonstrated mild inhibition of multiple CYPs in animal models include genistein, diadzein, and equol from soy, (5, 6) and theaflavins from black tea. (7)
Green tea extracts and the quercetin derivatives isoquercetin and rutin are an exception to most other flavonoids; green tea tannins can increase CYP activity, at least in vivo (8) as well as phase II activity (GST and UGT). Similarly, the quercetin derivatives were demonstrated to increase intestinal and liver CYPs in rats. (9)
Nrf2 is the gene that governs the production of detox proteins and enzymes. Activating Nrf2 activators is thus particularly useful as a wide variety of dietary components have been shown in vitro and in vivo to activate Nrf2 and directly increase activity of phase II enzymes. These include green tea’s epigallocatechin gallate (EGCG) (10), resveratrol (11), curcumin (12) and its metabolite tetrahydrocurcumin, which has greater phase II activity (13) cinnamaldehyde (14), caffeic acid phenyethyl ester, alpha lipoic acid (15), alpha tocopherol (16) lycopene (17), apple polyphenols (chlorogenic acid and phloridzin) (18), gingko biloba (19) chalcone (20) , capsaicin (21), hydroxytyrosol from olives (22), allyl sulfides from garlic (23) chlorophyllin (24), and xanthohumols from hops (25).
The beneficial effects of these phytochemicals have been demonstrated in numerous animal and human studies, particularly their chemopreventative and antioxidant abilities. Furthermore, these effects may be explained by their indirect stimulation of antioxidant enzyme production and phase II detoxification through Nrf2 signalling. (26) Dr Shade’s video clarifies this question (See link)
Isothiocyanates derived from glucosinolates are reactive sulfur compounds with potent chemopreventive properties. The prototypical member is sulforaphane, a constituent of broccoli that is the subject of several human cancer trials.
Isothiocyanates such as sulforaphane and indoles such as indole-3-carbinol (I3C) are among the most potent natural inducers of phase II detoxification enzymes. (27) Sulforaphane and a derivative of I3C both directly activate Nrf293, which increases the production of several protective enzymes, including GSTs, UGTs and even glutamate-cysteine ligase (which synthesizes glutathione), as well as NQO1. (28) I3C derivatives are also strong inducers of many phase I & II enzymes, and thus are among the most well studied phytochemicals for detoxification, as well as cancer prevention. (29-33)
Compounds from the Japanese horseradish Wasabi japonica (34, 35), and benzyl isothiocyanate (BITC) (36) from cruciferous vegetables similarly stimulate phase II enzyme activity via Nrf2 activation. Both sulforaphane and HITC also lower CYP activity. (37)
In this same vein, Sulfur constituents from garlic are inhibitors of various CYPs (38) and induce GST and NQO1 activity in gastrointestinal tissues in rats. (39)
Interestingly, by activating Nrf2, components in garlic were able to reverse the depletion of antioxidant enzymes caused by a toxic metal compound in the livers of laboratory rats. (40)
D-limonene (from citrus oil) has been investigated for anticancer activity in uncontrolled human trials and animal studies with some success. (41). Part of this chemopreventive activity is due to the induction of phase I and phase II enzymes. In rats, D-limonene has been shown to increase total CYP activity (42), intestinal UGT activity (43) and liver GST and UGT activity. (44-6)
Calcium D-glucarate is present in many fruits and vegetables, and can be produced in small amounts in humans. (47) When activated in the gut, it functions as an inhibitor of beta-glucuronidase, an enzyme produced by colonic bacteria and intestinal cells. In the intestines, beta-glucuronidase removes (deconjugates) glucuronic acid from neutralized toxins, essentially reversing the reaction catalyzed by UGTs. Deconjugation reverts the toxin to its previous dangerous form, and allows it to be reabsorbed. Elevated beta-glucuronidase activity has been associated with increased cancer risk. (48).
Chlorophyllin is a chlorophyll derivative (49) that inhibits CYP activity (50), and stimulates GST activity in cell culture and rodent models. (51) The unique chemical structures of chlorophyllin and chlorophyll enable them to bind and “trap” toxins in the gut preventing their absorption. In animal models, chlorophyllin and chlorophyll lower the bioavailability and accelerate the excretion of several environmental carcinogens. (52, 53) Toxin trapping may partly explain the results of a human trial of residents of Qidong, China, an area with a high incidence of liver cancer due to exposure to aflatoxin (a toxin produced by species of the fungus Aspergillus). Among the 180 people who took 100 mg of chlorophyllin three times daily, urinary levels of DNA-aflatoxin conjugates (a marker for DNA mutation) went down 55% compared to untreated people (54)
Probiotics: Certain strains of probiotic bacteria may minimize toxin exposure by trapping and metabolizing xenobiotics or heavy metals. (55)121 Examples include the detoxification of aflatoxin and patulin (two toxins produced by Aspergillus, a type of mold) (56), the metabolism of heterocyclic amines and dimethylhydrazine (57), and the binding of lead and cadmium. (58)
Additionally, the production of the short chain fatty acid butyrate by lactic acid bacteria (from the fermentation of dietary fiber) has been shown to stimulate GST production in intestinal cell culture; this may also contribute to some of the anticarcinogenic properties of dietary fiber. (59)
N-acetyl cysteine: N-acetyl cysteine is important because it can provide an alternative source of sulfur for glutathione production. It is a free radical scavenger on its own, effective at reducing oxidative stress, particularly due to heavy metal toxicity. (60) Because it can directly replenish glutathione stores, NAC is more effective than methionine at preventing liver damage,(61) and is the current treatment for acetaminophen toxicity. It is an effective treatment for acute liver failure due to non-acetaminophen drug toxicity as well. (62)
Milk Thistle (Silybum marianum), one of the most well-researched plants in the treatment of liver disease (63), contains a mixture of several related polyphenolic compounds called silymarin. Silymarin promotes detoxification by several complementary mechanisms. The antioxidant capacity of silymarin can lower the liver oxidative stress associated with toxin metabolism, particularly lipid peroxidation (64), which has the effect of conserving cellular glutathione levels. (65)
Similarly to NAC, silymarin can protect against acetaminophen toxicity (possibly by the similar mechanism of preserving glutathione levels). Silymarin, however, may be a more effective antidote than NAC for acetaminophen toxicity if the treatment is delayed (in an animal model, it was effective when administered up to 24 hours after overdose). (66)
Phase III Transporters
Phase III transporters are important for removing toxins from healthy cells, they are so efficient that they increase the clearance of synthetic pharmaceutical drugs, including, but not limited to chemotherapy drugs, to which phase III transporters enable cancer cells to become resistant. Big Pharma has of course spent billions to circumvent Nature’s protection mechanisms. Be that as it may, if a person is taken cytotoxic chemo and wants to try it out, his or her oncologist will recommend to inhibit Phase III stimulation.
Dietary factors can have differing effects on phase III transporters. For example, apple polyphenols (67) and sulforaphane (at levels equivalent to about two servings of broccoli (68)) both stimulate the activity of the phase III proteins. In contrast, the curcumin metabolite tetrahydrocurcumin decreases the activity of the phase III transporters in human cervical carcinoma and breast cancer cell lines. (69) Resveratrol decreases phase III protein synthesis which prevented acute myeloid leukemia cells from becoming resistant to the chemotherapy drug doxorubicin in cell culture. (70). Hence, quality red wine before a chemo blast may be indicated if the patient wants the full poison effect of the chemo. Silibinin, the chief constituent of milk thistle (71) is also a phase III inhibitor, both in vitro and in vivo. (72)
As a major carrier of toxins from the body, proper bile flow is a critical final step in the metabolic detoxification process. Impairment of bile flow (cholestasis), resulting from dysfunction within the liver or blockage of the bile duct, can result in the buildup of liver toxins and liver injury. Cholestasis can also be the result of the detoxification process itself. In this realm, there is increasing evidence that the detoxification and excretion of clinical drugs into the bile can produce cholestatic liver disease. (73)
Artichoke has been used for centuries in folk medicine as a liver protectant and to stimulate bile flow (choleresis), and is the best-studied herbal choleretic agent. Thus, if a patient really wants to ingest Big Pharm’s synthetic drugs, with the wine, (for the inhibition of the exit transporters), a few heads of artichokes may be indicated to help with the bile flow.
Furthermore, artichoke contains several antioxidants that can protect against oxidative liver damage, as well as caffeoylquinic acids, which have been shown to stimulate bile flow in animal models. (74) Caffeoylquinic acids may also be responsible for the choleretic properities of yarrow (75, 76) fennel (77) and dandelion. (78) Andrographis, garlic, cumin, ginger, ajowan (carom seed), and curry and mustard leaf have also been shown to stimulate bile flow or bile acid production in rodent models. (78-82)
Avoiding toxin/toxicant exposure
When it is not possible to eliminate toxin/toxicant exposure, there are ways to mitigate their effects and reduce their impact. First off, some kind of HEPA air filter should be used in homes. And efforts should be made at limiting or eliminating the introduction of VOCs in the home by using VOC-free cleaning products, low-VOC paints, and choosing throw rugs (or none at all) instead of new carpeting and the like. (83) Foods should be stored in glass and not in bisphenol A (BPA) or phthalate-full containers, most of which are made from plastics. Hemp, wood and ceramic containers can be good too if they don’t contain toxicants. Avoiding reheating foods in plastic containers and exposing plastic water bottles to heat and the sun is one of the worse things one can do in terms of these endocrine disruptors contaminating food and water.
Food-wise, it’s much better to have a garden or get organic produce. Because organic produce isn’t always pesticide free, a home garden is better, provided it is organic and distant from polluting sources. (84) Washing fruits or vegetables can decrease some pesticide residue, although it is not effective against all pesticide types (85), and commercial fruit and vegetable wash solutions may not be any more effective than water alone. (86) Peeling skins off of produce may help to further lower pesticide levels. Using baking soda is also good. Studies i’ve read actually claim it’s the best method to clean contaminated produce.
Refusing to consume processed foods is usually a good idea. Even ones that are free of synthetic preservatives may contain detectable amounts of toxic compounds that were introduced by chemical transformation, for example, during processing. Just about all animal foods that are not naturally and organic raised will have toxic loads of medication like antibiotics (which kill the good bacteria in the microbiota), growth hormones, mercury from vacination and the like, all of which are carcinogenic and hundreds of other deleterious molecules. With organic animal foods, one must be careful with molds and bacteria, as their endotoxins tend to be more virulent than plant-based bacteria. With processing, numerous toxins are produced by the high temperatures used to manufacture some processed food ingredients. (87)
To optimize the metabolic detoxification pathways, the body needs lots of quality water and quality phytonutrients, including, but not limited to sulphur-rich foods like broccoli, bok choy, kale, Brussels sprouts and other cruciferous plants. Because the microbiota contributes in the detox task, taking good care of this inner garden is indicated, hence the need for both quality probiotics and prebiotics. Fiber-rich foods are also highly recommended, if only to clear out toxic and carcinogenic substances that can stick to intestinal walls.
Putting in place the avoidance strategy mentioned above is recommended. In this perspective, adopting non-leaching quality stainless steel water bottles (not all stainless steel bottles are toxic-free) and glass containers like Pyrex to store food. Spring water and-or reverse-osmosis filters can be a solution for water quality.
Detoxing the home and body is essential. Walls are usually full of many toxicants like cancer-causing formaldehyde that comes from the gluing of the wood. If remodeling is not possible, opening the windows often is recommended, along with air filtration. Cloth, like the bedding and sofas are full of fireretards which affect the thyroid. Hence, today’s epidemics of thyroid diseases. Better to stick with organic coton, hemp, lin or other natural clean textiles. Stickless tyflon kitchen-ware super toxic like microwave ovens, better to ditch these. Household items like vinegar and baking soda can be used to clean the kitchen while coconut and organic olive oil with essential oils make excellent skin care products. (Check out EWG’s Skin Deep guide for detailed information on safe ingredients for both home and beauty products).
With arsenic (even found in the cheaper wines), mercury is one of the three big heavy metals that significantly contributes to chronic diseases epidemics. For those eating Mediterranean, staying with smaller fish like sardines, herring, archovies (anchois) or cold water fish like the smaller salmon can be ok. But because even small fish have heavy metals, ingesting some of the detox foods mentioned above is indicated, as this will reinforce the detox pathway, in particular the gluthetione pathways which thrive with the cruciferous vegetable family.
By choosing organic fruits and vegetables, one can minimize environmental toxin exposure. The EWG has a list of fish that are low in mercury, plus you can use their Dirty Dozen and Clean 15 lists of fruits and veggies to cut out other toxins from the food. Starting at the lowest level of the food supply is always a good idea. Hence, better to get one’s DHA (long chain omega 3 essential fatty acid) from algae, as that is where the planktons and the fishes’ DHA comes from. It is thus more pure.
Exercising and sweating is also indicated, as this helps to rid your body of toxins. Saunas, yoga and walking are great. No need for intense gymnastics. But a once a week strength fitness exercise session does wonders to boost endorphins and testosterone as well as other biochemical pathways. Because testosterone is a rejuvenation hormone, the entire metabolism will function better.
Unless one lives in a pristine isolated mountain area where the soil is still rich in humus and healthy bacteria and worms, and hence the food high in quality, it may be indicated to take high-quality supplements to support the three Phases of the metabolic detoxification processes, including but not limited to magnesium, selenium, zinc, vitamin C, and vitamin B complex, as well as special glutathione-boosting compounds like as N-acetyl-cysteine, alpha-lipoic acid, and milk thistle, inter alia.
Getting chelated via a medical doctor can be indicated for those who live in toxic urban centers where the pollution is high. Medical therapy with heavy metal chelators can lower mercury, lead, arsenic, and other toxic metals. Edta is the common chelator, but there are others like DMPS, DMSA and more. Colonics and anemas can also be cool.
Key Synergistic Blends
With Melatonin, glutathione is one of the master antioxidant. It can also regenerate itself in the liver as needed, but key nutrients are necessary for this molecule to be synthesized.
As stated, glutathione building-blocks are especially found in the cruciferous family as well as a few other sources like avocados and spinach. However, one of the dietary challenges we have with glutathione-enhancing foods is that digestive enzymes can break them down before they can be absorbed. But by eating lots of glutathione producing foods, many of the key nutrients survive the intestinal juices and all the more so that these nutrients will increase the body’s own capacity to produce glutathione. Some of these nutrients include selenium, vitamin E, cruciferous vegetables, alpha-lipoic acid, milk thistle, and N-acetyl cysteine.
Vitamin C is also important in liver detoxification pathways. It helps protect liver detoxification enzymes, created in phase I and phase II of the liver detoxification pathways, from oxidative damage. Vitamin C equally helps to protect liver tissues from oxidative damage. Some research also suggests that vitamin C may play a role in toxin removal.
In terms of production, vitamin C is tightly controlled in the body. Blood levels are mainly determined by vitamin C intake and kidney regulation. Research shows that some phytochemicals may increase plasma vitamin C, even in the absence of vitamin C consumption.
To be on the safe side, it’s a good idea to take a few grams of Vitamin D3 whenever there is significant exposure to toxicants, in association with vitamin C rich foods.
Companies that make dietary supplements like Hepasil DTX have tested the synergy of a few of these nutrients in specific proportions. (See below Exhibit A). However, the H.M. Institute is of the opinion that proper smoothie blends with specific superfoods and nutrients is a superior technique because it is by nature holistic, meaning it allows the body to use what it needs while boosting the body’s capacity to get the detox Job done under the best conditions that 65 million years of biological evolution has fine-tuned. But for this to occur, it is indispensable to feed the body the right high-vibrancy foods without Society’s toxicants that inhibit all phases of the metabolic detoxification pathways.
Ch Joubert (H.M. Institute, Director)
Clinical Research on Increasing Glutathione Production
Scientists conducted a double-blind, placebo-controlled study on multiple blends of nutrients. The purpose was to determine if they promoted increases in plasma glutathione and vitamin C.
The study intervention group used the product Hepasil DTX™, provided by USANA Health Sciences. (Source) Hepasil DTX contains biotin, choline, milk thistle extract, N-acetyl L-cysteine, alpha-lipoic acid, broccoli concentrate, green tea extract, olive fruit extract, and turmeric extract. Fifteen healthy volunteers participated in the study. Subjects were given Hepasil DTX or placebo for 28 days. On days 1, 14, and 28, blood samples were drawn to measure plasma vitamin C and glutathion
Study Results: Hepasil DTX increased plasma glutathione two hours following the first treatment and significantly increased plasma glutathione eight hours after treatment. Plasma glutathione levels increased 74 percent by the end of the study. Hepasil DTX significantly increased plasma vitamin C as soon as two hours following the first treatment. This was maintained during the entire acute phase (0-8 hour time points) The results thus showed a synergistic effect of these nutrients. The treatment formula boosted both glutathione and vitamin C levels. It upregulated the body’s ability to utilize glutathione in detoxification reactions. It also increased the body’s antioxidant capacity.
A follow-up report showed that the increases in both glutathione and vitamin C have clinical benefits. Subjects taking Hepasil DTX were significantly more resistant to oxidative damage than those taking the placebo.
See Hepasil DTX™ Increases Antioxidant and Detoxification Capacity by Boosting Glutathione and Vitamin C (Source)
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