- 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 Section C
- 13 General Recommendations
- 14 Glutathione
- 15 Vitamin C
- 16 Clinical Research on Increasing Glutathione Production
- 17 Study Results
- 18 Study Conclusion
- 19 Reference and Precision Sources
- 20 Reference and Precision Notes
- 21 Section B
- 22 Avoiding toxin/toxicant exposure
- 23 Below, a general Heavy Metal Detox Protcol
Both metabolic and holistic detoxification 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 on the Science of Healing Holistically (Section C).
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, while important for removing toxins from healthy cells, can also decrease the effectiveness of pharmaceutical therapies by increasing their clearance. This can be especially problematic with chemotherapy drugs, to which phase III transporters enable cancer cells to become resistant. Therefore, stimulation of phase III activity may not always be desirable.
Dietary factors can have differing effects on phase III transporters. For example, apple polyphenols133, and sulforaphane (at levels equivalent to about two servings of broccoli)134 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.135 Resveratrol decreases phase III protein synthesis which prevented acute myeloid leukemia cells from becoming resistant to the chemotherapy drug doxorubicin in cell culture.136 Silibinin, the chief constituent of milk thistle137, is also a phase III inhibitor, both in vitro and in vivo.138
Bile flow: 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; there is increasing evidence that the detoxification and excretion of clinical drugs into the bile can produce cholestatic liver disease.139 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.
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.140 Caffeoylquinic acids may also be responsible for the choleretic properities of yarrow141,142, fennel143, and dandelion.144 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.145,146,147,148
1. To optimize the metabolic pathways, the body needs quality phytonutrients, in particular sulphur-rich foods like broccoli, bok choy, kale, Brussels sprouts and other cruciferous plants. to maximize your dietary phytonutrients and increase your body’s ability to detoxify. Choose foods high in antioxidants like dark, green leafy veggies and berries. Garlic and onions can also help you detoxify.
Avoid plastics. I recommend non-leaching stainless steel water bottles and glass containers like Pyrex to store leftovers. Instead of buying water in plastic bottles, install a filter at home. I like zero-waste reverse-osmosis filters.
Detox your home and body. Stick with natural, simple products. Household items like vinegar and baking soda can be used to clean your kitchen while coconut oil and brown sugar make excellent skin care products. If you can eat it you know it’s safe to put on your skin! Also, check out EWG’s Skin Deep guide for detailed information on safe ingredients for both home and beauty products.
Stop eating mercury. For those eating Mediterranean, Stick with smaller fish like sardines or cold water fish like the smaller salmon, which have lower mercury levels. Choose organic fruits and vegetables to 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 your food (you can read about toxins and weight gain in one of my previous blog posts).
Exercise and sweat. Exercising and sweating help rid your body of toxins. Get moving and try a sauna or steam bath.
Take high-quality supplements to support detoxification including zinc, vitamin C, and vitamin B complex, as well as special glutathione-boosting compounds such as N-acetyl-cysteine, alpha-lipoic acid, and milk thistle.
Get chelated. Medical therapy with heavy metal chelators can lower mercury, lead, arsenic, and other toxic metals. You’ll want to work closely with a Functional Medicine practitioner if you suspect heavy metals are an issue.
Address toxicity in your home. If you suspect lead or other poisons in paint, floors, or insulation, consult an expert to remove sources of heavy metals and other toxins.
Glutathione is so important for humans, it is known as the “master antioxidant.” It is called this, because it is the most abundant antioxidant in the body and it can regenerate itself in the liver.
Glutathione is found in asparagus, avocado, spinach, broccoli, and, among other sources, some supplements. Sadly, food sources of glutathione are poorly absorbed into the body. Digestive enzymes can break it down before it can be absorbed. There is also no direct transport system for glutathione. (See the Document on Detox enhancement techniques).
Although glutathione is poorly absorbed, diet does play a part in the body’s levels. The body needs key building blocks to manufacture glutathione. Certain foods and nutrients are known to provide them. Eating these building blocks can increase the body’s production of glutathione. These 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 liver detoxification pathways, from oxidative damage. Vitamin C helps protect liver tissues from oxidative damage. Some research also suggests that vitamin C may play a role in toxin removal.
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.
Clinical Research on Increasing Glutathione Production
Scientists conducted a double-blind, placebo-controlled study on a blend 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. 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 glutathione.
- 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 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.
The results back up previous research showing that some phytochemicals may increase plasma vitamin C, even in the absence of vitamin C consumption. It also offers a specific blend of ingredients that can be used to increase the body’s glutathione production.
Reference and Precision Sources
- Hepasil DTX™ Increases Antioxidant and Detoxification Capacity by Boosting Glutathione and Vitamin C (1)
- Hepasil DTX™ Increases Antioxidant and Detoxification Capacity by Boosting Glutathione and Vitamin C (2)
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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. (13) Foods should be stored in glass and not in bisphenol A (BPA) or phthalate-full containers, most of which are made from plastics. Hemp and ceramic containers can be good too. 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. (14) Washing fruits or vegetables can decrease some pesticide residue, although it is not effective against all pesticide types (15), and commercial fruit and vegetable wash solutions may not be any more effective than water alone. (16) Peeling skins off of produce may help to further lower pesticide levels. Using baking soda is also good.
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. In this perspective, numerous toxins are produced by the high temperatures used to manufacture some processed food ingredients. (17)
13. Crinnion MJ. Environmental Medicine, Part 2 – Health Effects of and Protection from Ubiquitous Airborne Solvent Exposure. Altern Med Rev 2000;5 (2) : 133-143
14. Crinnion MJ. Environmental Medicine, Part 4: Pesticides – Biologically Persistent and Ubiquitous Toxins. Altern Med Rev 2000;5 (5) : 432-447
15. Štěpán R. , Tichá J. , Hajšlová J. , Kovalczu, T. and Kocourek V. Baby food production chain: pesticide residues in fresh apples and products. Food Addit Contam 2005; 22 (12):1231-42
16. Krieger RI, Brutsche-Keiper P, Crosby HR, Krieger AD. Reduction of pesticide residues of fruit using water only or Plus Fit Fruit and Vegetable Wash. Bull Environ Contam Toxicol 2003;70(2): 213-8
17. Borchers A, Teuber SS, Keen CL, Gershwin M. Food safety. Clin Rev Allergy Immunol 2010;39 (2) : 95-141