toxic11Part I, Part II, and now Part III. It’s my very own version of a cleansing trilogy!

Ok, bad reference, but I’m on a plane right now at 21,000 ft. I’m making my journey to the ultimate geek gathering consisting of all the amazingly cool functional medicine innovators for the hormone module. Hence to say, I’m a little giddy. Anyway, focusing on staying clean in a world of toxic soup can be kind of dreary, not to mention exhausting when you consider everywhere you go there’s another bug-a-boo of a toxin ready to enter your body and wreck its unwelcome havoc. Thankfully, the fatigue that comes with being proactive and educating yourself on avoidance will be lifted as your body’s burden is lightened through decreasing the amount of chemicals, pesticides, herbicides, plastics, and other various toxicants.

In the previous blogs, I reviewed key strategies to avoid the “re-tox” after detox, and included tools for doing just that. Now, it’s time to review some specifics to successfully transition you from post-cleanse into a healthy, happy maintenance program.

 

What Happens With Detoxifying

It may be helpful (and fun) for you to understand some background of how our body rids itself of these xenobiotics (chemicals that are outside of normal metabolism) so you can understand the biochemistry behind various supportive measures for staying lean and clean. As a side note, if you really want to impress your friends at the beach parties, another name of what I’m about to describe is biotransformation.

Most of what we know regarding detoxification and cleansing is based on drug metabolism and pharmokinetics (what the body does to a drug as it moves throughout the body and is excreted). This involves multiple steps in which primarily nonpolar, lipid-soluble toxins (from drugs, metals, food additives, pollutants, household cleaners, bacterial endotoxins, etc.) are biotransformed into polar, water-soluble, components for excretion. This process mostly takes place in the liver and intestines.1-6 It was R.T. Williams in 1947 who proposed how compounds could be transformed in two phases. These two steps involve enzymatic processing pathways and are referred to as phase I, in which oxygen was used to form a reactive site, and phase II, in which a water-soluble group was added to the reactive site (conjugation).5-6

During evolution, species have evolved these multiple enzymes to assist with the elimination process of the toxins that appeared in our environment. Interestingly, there is evidence of genetic adaptation to environmental toxins through variation of these enzymes for survival. This was made evident most recently with a study of inhabitants in the northern Argentinean Andes, an area where elevated levels of arsenic are common. In this study, researchers genotyped this population to assess for a protective variant in a gene by evaluating over 4 million single nucleotide polymorphisms (SNPs). The authors found a connection between the AS3MT (arsenic [+3 oxidation state] methyltransferase) gene and levels of mono- and dimethylated arsenic in the urine, indicating that this Argentinean population exhibited great ability to deal with this environmental toxin through prolonged exposure and resultant natural selection.7-8

This survival mechanism, however, is not optimal for everyone. That is, even with exposure to toxins, some people do not exhibit more robust responses, and their variability affects their capacity to metabolize these toxicants, making them more susceptible to disease processes. For example, there have been associations with various exposures and impaired detoxifying capabilities in relationship to expression of cancer, autism, Parkinson’s and neurodegenerative diseases, fibromyalgia, and chronic fatigue/immune dysfunction.9-12

The study of nutrigenomics and epigenetics is providing more understanding of these essential processes and the results aren’t always as favorable as seen with the Argentina population. For example, there is evidence that epigenetic alternations affecting a variant in glutathione S-transferase P1 (GSTP1), a phase II enzyme that utilizes the potent antioxidant glutathione as a substrate, can impact various cancer risks.13-14

Another example is a SNP in CYP2D6, a phase I enzyme which can cause one to be a “slower detoxifier.”5 Additionally, methylation issues and other genetic variants such as MS (methionine synthase), COMT (catechol-O-methyltransferase), methyltransferases, STM1, GSTP1 (glutathione transferases), APOE 4 (apolipoprotein E 4), and/or impaired metallothionein function can also impede optimal removal of toxins and increase their retention after exposure.

Most people probably know they are poor detoxifiers and report that they seem to be “hyper-reacting” to environmental cues. If this is true, assessing detoxification genomic markers can be incorporated as a helpful adjunct to your wellness protocol in which various nutrients can be used to support the genetic susceptibility. I am one of these unfortunates, along with many of my clients, and we tend to do well with continual support in detoxification using some of the nutrient support I list below.

 

Keeping the Pathways Open for Elimination

Regardless of susceptibility or adaptation, various metabolic pathways and xenobiotic-metabolizing enzymes require cofactors to effectively detoxify. Although some practitioners may confer there is no “evidence” for supporting cleansing and detoxification, basic review of pharmokinetics and phase I (the cytochrome P450 enzymes) and phase II (conjugation pathways) provide examples of various nutrients and phytochemicals that are needed to effectively move toxicants through the pathways and into the bile for excretion in the feces or into the kidneys through the urine.

For example, during phase I reactions in the liver, reactive oxygen species can form as a byproduct, which may lead to cellular damage. Therefore, to quench potential detrimental effects, antioxidants from plant derivatives such as carotenoids (which may also induce phase II response through antioxidant response elements (ARE))15, ascorbic acid, tocopherol, selenium, copper, zinc, manganese, coenzyme Q10, thiols (found in garlic, onions, and cruciferous vegetables), bioflavonoids, silymarin, and other various nutrients (n-acetylcysteine, a-lipoic acid, polyphenols, and curcumin) can be utilized.

In order to effectively modulate phase II conjugation, glucuronidation support (calcium d-glucarate), sulfur containing compounds, glutathione, various amino acids (taurine, glycine, arginine, glutamine, serine, and proline), and acetyl and methyl groups need to be made available. This means that bioavailable amino acids, such as those found in whey and pea protein, can be utilized to effectively supply nutrients for detoxification. Whey protein provides the benefit of up-regulating glutathione with immunomodulatory actions, whereas adding legumes, such as pea protein, to the diet may result in the added benefit of the reduction in pro-inflammatory markers such as CRP and C3, and an improvement in some metabolic features (lipid profile and BP).16

 

Keeping Lean

Obtaining optimal levels of protein and fiber can also assist with satiety,17-18 intestinal health, and healthy weight after a post-cleanse release of toxic fat. Other supportive nutrients for assisting metabolic rate and optimizing fat burning can be used. Example include carnitine,19 EGCg, naringenin, hesperetin,20-22 and modulating cravings with GABA, 5-HTP, and l-tyrosine for calming the brain and modulating dopamine. It is always a wise idea to have neurotransmitters assessed or to do a brain survey when implementing neurotransmitter support.

Finally, more attention has been being placed on phase III detoxification. Phase III transporters which are present in many tissues, including the liver, intestines, kidneys, and brain. There, they provide a barrier against xenobiotic entry, or a mechanism to move toxicants and microbes (xenobiotics and endobiotics) in and out of cells. This is why its important to keep all entries clear. Basically, this means that in order to optimize phase I and II, you want to avoid excess exposures and ensure your poo is regular. You don’t want your liver to clear all the crude and then have your body pump it right back out! This is where those little critters and supporting intestinal integrity comes in.

 

Don’t Forget Your Trillion Little Friends!

We cannot, will not, and should not, overlook the power of our microbiome for anything, this is my motto. These little critters never cease to amaze me at their multitasking mastery of our biochemistry, and detoxification is no different. A 2008 study demonstrated that Bifidobacterum breve and Lactobacillus casei helped rid rats of Bisphenol A, a nasty plastic linked to obesity.23

So, by keeping clean, eating lean protein, and supporting your biochemical pathways, you can stay lean and healthy post-cleanse and not worry about re-toxin’!

 

References

  1. Croom E. Metabolism of xenobiotics of human environments. Prog Mol Biol Transl Sci. 2012;112:31-88. doi: 10.1016/B978-0-12-415813-9.00003-9.
  2. Lang M1, Pelkonen O. Metabolism of xenobiotics and chemical carcinogenesis. IARC Sci Publ. 1999;(148):13-22.
  3. Anzenbacher P1, Anzenbacherová E. Cytochromes P450 and metabolism of xenobiotics. Cell Mol Life Sci. 2001 May;58(5-6):737-47.
  4. Dhakshinamoorthy S1, Long DJ 2nd, Jaiswal AK. Antioxidant regulation of genes encoding enzymes that detoxify xenobiotics and carcinogens. Curr Top Cell Regul. 2000;36:201-16.
  5. Cline JC. Nutritional Aspects of Detoxification in Clinical Practice. Review Article. Alternative Therapies. May/June 2013; 21.3: 54-62.
  6. Liska DJ. The Detoxification Enzyme Systems. Altern Med Rev.1998;3(3):187-198)
  7. Schlebusch CM, Gattepaille LM, Engstrom K, Vahter M, Jakobsson M, Broberg K. Human Adaptation to Arsenic-Rich Environments. Mol Biol Evol. March 3, 2015. doi: 10.1093/molbev/msv046
  8. Alcock J. Human evolution and arsenic detoxification. The Evolution & Medicine Review. Mar 7th, 2015. Available at: http://evmedreview.com/?p=2495#sthash.wW5yENta.dpuf
  9. Anna Lukaszewicz-Hussain. Role of oxidative stress in organophosphate insecticide toxicity – Short review. Pesticide Biochemistry and Physiology. October 2010; 98(2): 145–150,
  10. Shelton JF, Hertz-Piccotto I, Pessah IN. Tipping the Balance of Autism Risk. Potential Mechanisms Linking Pesticides and Autism. Environmental Health Perspectives. 2012;120(7):944-951.http://www.medscape.com/viewarticle/767013_5
  11. D’Amelio M, Ricci I, Sacco R, Liu X, D’Agruma L, Muscarella LA, Guarnieri V, Militerni R, Bravaccio C, Elia M, Schneider C, Melmed R, Trillo S, Pascucci T, Puglisi-Allegra S, Reichelt KL, Macciardi F, Holden JJ,Persico AM. Paraoxonase gene variants are associated with autism in North America, but not in Italy: possible regional specificity in gene-environment interactions. Mol Psychiatry. 2005 Nov;10(11):1006-16.
  12. Hernández AF1, Lacasaña M, Gil F, Rodríguez-Barranco M, Pla A, López-Guarnido O. Evaluation of pesticide-induced oxidative stress from a gene-environment interaction perspective. Toxicology.2013 May 10;307:95-102. doi: 10.1016/j.tox.2012.09.007. Epub 2012 Sep 29.http://www.ugr.es/~fgil/ficheros/publicaciones/Toxicology_2013.pdf
  13. Schnekenburger M, Karius T, Diederich M. Regulation of epigenetic traits of the glutathione S-transferase P1 gene: from detoxification toward cancer prevention and diagnosis. Frontiers in Pharmacology. 2014;5:170. doi:10.3389/fphar.2014.00170.
  14. Beutler E. Nutritional and metabolic aspects of glutathione. Annu. Rev. Nutr. 1989; 9:287-302.
  15. Ben-Dor, A, Steiner M, Gheber L, Danilenko M, Dubi N, Linnewiel K, Zick A, Sharoni Y, Levey J. Carotenoids activate the antioxidant response element transcription system. Mol Cancer Ther. January 2005 4; 177. http://mct.aacrjournals.org/content/4/1/177.long
  16. Hermsdorff HH1, Zulet MÁ, Abete I, Martínez JA. A legume-based hypocaloric diet reduces proinflammatory status and improves metabolic features in overweight/obese subjects. Eur J Nutr. 2011 Feb;50(1):61-9.
  17. Anderson GH, Moore SE. Dietary proteins in the regulation of food intake and body weight in humans. J Nutr2004;134:974S-9S.
  18. Leidy HJ, et al. Beneficial effects of a higher-protein breakfast on the appetitive, hormonal, and neural signals controlling energy intake regulation in overweight/obese, “breakfast-skipping,” late-adolescent girls. Am J ClinNutr. 2013 Apr;97(4):677-88. doi: 10.3945/ajcn.112.053116. Epub 2013 Feb 27.
  19. Kelly GS. L-Carnitine: therapeutic applications of a conditionally-essential amino acid. Altern Med Rev. 1998 Oct;3(5):345-60. Review. http://www.ncbi.nlm.nih.gov/pubmed/9804680
  20. Jung UJ1, Lee MK, Park YB, Kang MA, Choi MS. Effect of citrus flavonoids on lipid metabolism and glucose-regulating enzyme mRNA levels in type-2 diabetic mice. Int J Biochem Cell Biol.2006;38(7):1134-45. Epub 2006 Jan 6.
  21. Jung UJ1, Lee MK, Jeong KS, Choi MS. The hypoglycemic effects of hesperidin and naringin are partly mediated by hepatic glucose-regulating enzymes in C57BL/KsJ-db/db mice.J Nutr.2004 Oct;134(10):2499-503.
  22. Fukuchi Y, Hiramitsu M, Okada M, et al. Lemon Polyphenols Suppress Diet-induced Obesity by Up-Regulation of mRNA Levels of the Enzymes Involved in ?-Oxidation in Mouse White Adipose Tissue. Journal of Clinical Biochemistry and Nutrition.2008;43(3):201-209. doi:10.3164/jcbn.2008066.
  23. Oishi K, Satao T, Yokoi W, Yoshida Y, Ito M, Sawada, H. Effect of Probiotics, Bifidobacterium breve and Lactobacillus casei, on Bisphenol A Exposure in Rats. Bioscience, Biotechnology, and Biochemistry. 2008; 72(6). 72, Issue 6, 2008.