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THE INTEGRATIVE · 2017-02-19 · THE INTEGRATIVE RD What is a “Detoxification Diet” ... and...
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www.integrativeRD.org Spring 2012 Volume 14, Issue 4 Contents THE INTEGRATIVE RD What is a “Detoxification Diet” ......................................... 68 Hepatic Detoxification An Overview ........................ 73 CPE Objectives and Questions ........................................ 77 CPE Certificate ..................... 78 Detoxification In Practice ............................. 79 Functional Laboratory Assessment of Detoxification and Biotransformation A Commentary .................... 82 Laboratory Testing Handout Part 1 ........................................... 85 Part 2 ........................................... 86 Adult Toxin Exposure Questionnaire ..................... 91 Resource Reviews: Therapeutic Fasting ................. 94 The Happiness Diet .................. 94 ALOX5 Gene Variants Affect Eicosanoid Production and Response to Fish Oil Supplementation...................... 95 HOT Nutritional Genomics Research Publications.............. 97 Chair’s Corner ................ 98 Editor’s Notes .................... 99 2011-2012 Leadership Contact Information..... 100 Upcoming Issues • Fall 2012 Editor’s Deadline, July 15, 2012 • Winter 2013 Editor’s Deadline, Nov. 1, 2012 Spring 2012 Volume 14, Issue 4 Jeffery S. Bland, Ph.D. D etoxification is a fundamental metabolic process encoded by more than one hundred genes, ex- pressing enzymes that comprise the phase 1, 2, and 3 detoxifica- tion processes. 1 When discovered in the late 1960s, these enzymes were thought to be in- volved primarily in drug metabolism but were quickly recognized to be critically involved in both general xenobiotic metabolism and metabolic biotransformation of hormone and intermediary metabolites. 2 As such, this system of biotransformation/detoxification enzymes is responsible for the control of in- termediary metabolism, as well as protection of the organism against exposure to and ad- verse metabolic consequences of external (exo) and internal (endo) toxins, ranging from foreign chemicals to enteric bacteria-related endotoxins. 3 The process of metabolic detoxi- fication takes place primarily in the gastroin- testinal and hepatic systems and is involved in the “first pass” detoxification of drugs, xe- nobiotics and substances produced in the gastrointestinal tract. It is important to note that any substance that accumulates in the body’s tissues can potentially become a toxin and, above a certain threshold concentration, can impair metabolic function. An example of this is the cellular metabolite lactic acid. Under normal metabolic conditions, its concentration is controlled within cells, and it does not have a deleterious effect on the organism. However, under certain conditions, such as enhanced lactic acid production during extreme physi- cal exertion, or slowed lactic acid metabolism as a side-effect of some drugs, lactic acid can build up in tissues, resulting in muscle pain, low energy, and central nervous system ab- normalities. Many potentially toxic substances are lipid soluble and can bioaccumulate in lipid-rich tissues. Through the phase 1 cytochrome P450 (CYP450) and phase 2 conjugation sys- tems, these lipid soluble toxic substances are converted into water soluble metabolites that can be excreted in the urine or feces. The phase 1 CYP450 system is made up of nearly a hundred different enzymes, each with dif- ferent affinities for specific substrates. 4 The genes that both encode and control the ex- pression of these CYP450 enzymes have been found to be highly polymorphic. In other words, numerous single nucleotide polymor- phisms (SNPs) have been identified within this family of enzymes, which translates clini- cally into slow, intermediate and fast detoxi- fication phenotypes. 5 This has resulted in the concept of the “yellow canary syndrome” — the name applied to individuals with a genet- ically regulated slow metabolism of specific substances, thus increasing the potential for these individuals to have an adverse response at a lower level of exposure to the substanc- es. 6 Recent information suggests that the genetically controlled detoxification system demonstrates a larger inter-individual varia- tion in function than any other metabolic process; the difference in first phase metabo- lism for a specific substance can vary as much as 1000-fold among healthy individuals. 7 The phase 2 conjugation reactions involved in detoxification include glucuronic acid con- jugation, sulfation, amino acid conjugation, methylation, acetylation, and glutathione conjugation. 8 The phase 2 enzymes convert the biotransformed intermediates produced by CYP450 metabolism into water soluble fi- nal products that can be safely excreted. What is a “Detoxification Diet”? continued on page 69
Transcript of THE INTEGRATIVE · 2017-02-19 · THE INTEGRATIVE RD What is a “Detoxification Diet” ... and...
www.integrativeRD.orgSpring 2012 Volume 14, Issue 4
Contents
THE INTEGRATIVERD
What is a “Detoxification Diet” .........................................68
Hepatic DetoxificationAn Overview ........................ 73
CPE Objectives and Questions ........................................77
CPE Certificate ..................... 78
Detoxification In Practice ............................. 79
Functional Laboratory Assessment of Detoxification and Biotransformation A Commentary .................... 82
Laboratory Testing HandoutPart 1 ........................................... 85Part 2 ........................................... 86
Adult Toxin Exposure Questionnaire ..................... 91
Resource Reviews:Therapeutic Fasting ................. 94
The Happiness Diet .................. 94
ALOX5 Gene Variants Affect Eicosanoid Production and Response to Fish Oil Supplementation...................... 95
HOT Nutritional Genomics Research Publications .............. 97
Chair’s Corner ................98
Editor’s Notes .................... 99
2011-2012 Leadership Contact Information .....100
Upcoming Issues• Fall 2012
Editor’s Deadline, July 15, 2012• Winter 2013
Editor’s Deadline, Nov. 1, 2012
Spring 2012 Volume 14, Issue 4
Jeffery S. Bland, Ph.D.
Detoxification is a fundamental metabolic process
encoded by more than one hundred genes, ex-pressing enzymes that
comprise the phase 1, 2, and 3 detoxifica-tion processes.1 When discovered in the late 1960s, these enzymes were thought to be in-volved primarily in drug metabolism but were quickly recognized to be critically involved in both general xenobiotic metabolism and metabolic biotransformation of hormone and intermediary metabolites.2 As such, this system of biotransformation/detoxification enzymes is responsible for the control of in-termediary metabolism, as well as protection of the organism against exposure to and ad-verse metabolic consequences of external (exo) and internal (endo) toxins, ranging from foreign chemicals to enteric bacteria-related endotoxins.3 The process of metabolic detoxi-fication takes place primarily in the gastroin-testinal and hepatic systems and is involved in the “first pass” detoxification of drugs, xe-nobiotics and substances produced in the gastrointestinal tract.
It is important to note that any substance that accumulates in the body’s tissues can potentially become a toxin and, above a certain threshold concentration, can impair metabolic function. An example of this is the cellular metabolite lactic acid. Under normal metabolic conditions, its concentration is controlled within cells, and it does not have a deleterious effect on the organism. However, under certain conditions, such as enhanced lactic acid production during extreme physi-cal exertion, or slowed lactic acid metabolism as a side-effect of some drugs, lactic acid can build up in tissues, resulting in muscle pain,
low energy, and central nervous system ab-normalities.
Many potentially toxic substances are lipid soluble and can bioaccumulate in lipid-rich tissues. Through the phase 1 cytochrome P450 (CYP450) and phase 2 conjugation sys-tems, these lipid soluble toxic substances are converted into water soluble metabolites that can be excreted in the urine or feces. The phase 1 CYP450 system is made up of nearly a hundred different enzymes, each with dif-ferent affinities for specific substrates.4 The genes that both encode and control the ex-pression of these CYP450 enzymes have been found to be highly polymorphic. In other words, numerous single nucleotide polymor-phisms (SNPs) have been identified within this family of enzymes, which translates clini-cally into slow, intermediate and fast detoxi-fication phenotypes.5 This has resulted in the concept of the “yellow canary syndrome” — the name applied to individuals with a genet-ically regulated slow metabolism of specific substances, thus increasing the potential for these individuals to have an adverse response at a lower level of exposure to the substanc-es.6 Recent information suggests that the genetically controlled detoxification system demonstrates a larger inter-individual varia-tion in function than any other metabolic process; the difference in first phase metabo-lism for a specific substance can vary as much as 1000-fold among healthy individuals.7
The phase 2 conjugation reactions involved in detoxification include glucuronic acid con-jugation, sulfation, amino acid conjugation, methylation, acetylation, and glutathione conjugation.8 The phase 2 enzymes convert the biotransformed intermediates produced by CYP450 metabolism into water soluble fi-nal products that can be safely excreted.
What is a “Detoxification Diet”?
continued on page 69
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The “total load” concept
There is potential for competition among different substrates for biotransformation by the same detoxification enzymes.9 This competition among various substances poses a risk for impaired detoxification due to overloading specific steps in the phase 1 or phase 2 processes, which then exceeds the capacity of the system to manage the “total load” of exposure.10 This has been observed clinically with various potential adverse drug-drug in-teractions, such as amiodarone for heart rhythm problems and simvastatin for elevated serum cholesterol. Another ex-ample—and the most common cause of emergency room visits for poisoning—is the consumption of alcohol while taking the over-the-counter drug acetamino-phen.11
The discovery that diet and specific foods influence detoxification
The field of detoxification/biotransforma-tion took a big step forward in the 1970s with the recognition that diet could have an important impact on the phase 1 and 2 enzyme systems.12 It was first recog-nized that adequate calorie and protein consumption is necessary to support de-toxification.13 Animal models indicated that certain constituents in vegetables and fruits stimulated intestinal drug me-tabolism.14 In 1978, it was reported that vegetarians had a more rapid first pass drug metabolism than omnivores, once again suggesting that certain dietary compositions and specific constituents of vegetable-rich diets were associated with increased detoxification.15 Controlled hu-man dietary intervention trials have con-firmed that consumption of vegetables at levels consistent with normal dietary intakes increases the rate of detoxifica-tion.16-18 It has also been shown that diets rich in plant foods that have an alkaline influence on the body enhance the excre-tion of biotransformed substances.19 Al-kalization of the urine can be achieved by consuming a diet that is high in alkaline ash foods, including vegetables, fruits and legumes. In contrast, diets high in animal proteins, sugars, fat and processed
foods are known to result in acidification of the urine, which is associated with a delayed excretion of biotransformed sub-stances.
From these discoveries, researchers have recognized that unique phytochemicals have specific influences on activation of phase 1, 2, and 3 biotransformation processes.20 Cruciferous vegetables, in-cluding cabbage, Brussels sprouts, broc-coli and cauliflower contain a family of phytochemicals termed glucosinolates. When digested, these compounds re-lease a number of secondary metabolites into the gut, such as sulforaphane, in-dole-3-carbinol, and phenylethyl isothio-cyanate.21 These secondary metabolites have been found to influence the genetic expression of both specific CYP450 and phase 2 enzyme systems.22 These phyto-chemicals are considered to be “bifunc-tional,” in that they simultaneously influ-ence the function of both the phase 1 and phase 2 biotransformation/detoxification enzymes.24 It is very important to achieve proper regulation in modulating phase 1 and phase 2 enzyme systems to produce a substance that can be readily excreted. This process is known as “balanced de-toxification.”
Other vegetable and fruit-derived phy-tochemicals, such as resveratrol from grapes, have also been found to have specific influences on phase 1, 2, and 3 biotransformation functions, as well as on the activation of the genomic antioxi-dant response element.25 It is interesting to note that the xenobiotic response el-ement (XRE), antioxidant response ele-ment (ARE), and metal response element (MRE) are all co-localized in the human genome, indicating that they share pro-moter activities. The XRE, ARE, and MRE control the expression of the genes in-volved in detoxification of foreign chemi-cals, protection against oxidant stress, and detoxification of toxic heavy metals, respectively. One of the central transcrip-tion factors induced by consumption of specific phytochemicals is nuclear regu-latory factor 2 (Nrf2), which activates the XRE, ARE and MRE. When activated by
specific phytochemicals, Nrf2 regulates the genetic expression of phase 1, 2, and 3 biotransformation and antioxidant en-zymes, such as glutathione peroxidase, peroxidase and catalase.
The mechanism of action of phyto-chemicals and their influence on de-toxification
The discovery of the cellular mechanism by which phytochemicals influence de-toxification has contributed to the un-derstanding of the important role that diet and foods have on biotransforma-tion. It is recognized that the relatively small amount of phytochemicals in a well-constructed food plan can have a much greater impact on cellular physiol-ogy than would be presumed from a tra-ditional “dose-response” pharmacology perspective.26 This enhanced activity has been termed “hormesis,” which means that the physiological impact of exposure at relatively low levels of dietary intake is amplified due to a unique mechanism of action. The proposed mechanism of ac-tion of phytochemicals has been termed “xenohormesis” by Sinclair.27 The xeno-hormetic mechanism is built around the recognition that specific phytochemicals influence intercellular signal transduc-tion and the induction of specific nuclear transcription factors. These nuclear tran-scription factors regulate the expression of unique families of genes, which in turn control critical cellular functions, such as xenobiotic detoxification, anti-oxidation, anti-inflammation, and metal detoxifica-tion. It is this influence of specific phyto-chemicals on important regulatory nodes within the genome of an individual that results in a unique metabolic response to exposures to foreign substances.
Cellular biology studies, animal model systems and human intervention trials have all demonstrated the important role of xenohormesis in modulating physio-logical function associated with biotrans-formation and detoxification.28-30 This development in our understanding of the role that diet and specific substances within foods play on intercellular signal transduction has been considered to be
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the seminal nutritional discovery of the 21st century, potentially rivaling the 20th century discovery of vitamins in its impor-tance for combating disease.31
Human clinical trials on detoxification diets and foods
The exciting developments in the field of nutrition related to metabolic bio-transformation and detoxification have been reinforced by a number of pub-lished human clinical trials. These studies have been built upon a solid foundation of basic cellular and animal science. As an example, it was shown that animals that were pre-treated with a nutritional mixture of phytochemicals were able to prevent acetaminophen-induced cellular injury by a xenohormetic increase in bio-transformation/detoxification and antiox-idant response.32 Another example is the evaluation of the influence of the crucif-erous vegetable-derived phytochemical indole-3-carbinol (I3C) and its companion diindolylmethane (DIM) on estrogen bio-transformation/detoxification and reduc-tion of breast cancer risk.33,34 Minich and Bland reviewed the history, safety and use of cruciferous vegetable phytochemicals in detoxification in 2007, concluding their therapeutic use to be both safe and effi-cacious based upon the studies.35
The Department of Molecular and Cel-lular Biology at MetaProteomics and the Functional Medicine Clinical Research Center recently conducted a human clini-cal trial investigating the influence of a phytochemically-enriched diet on de-toxification enzyme systems. Their results demonstrated the effectiveness of this intervention in both enhancing specific detoxification function through activa-tion of genetic expression and reducing clinical symptoms associated with fibro-myalgia.36
A recent series of published clinical tri-als studied the effects of phytochemical supplementation in patients with meta-bolic disturbances associated with insu-lin resistance. Both the control groups and the intervention groups consumed a low glycemic load Mediterranean diet
high in phytochemically-dense foods. The treatment groups received phytochemi-cal supplementation and had a statisti-cally significant improvement in multiple physiological markers associated with biotransformation function.37-39 The phy-tochemical supplementation came in the form of a food concentrate contain-ing specific rho-iso-alpha acids from the common hops plant (Humulus lupulus L.) and polyphenol-containing extract from Acacia nilotica, along with soy-de-rived phytosterols. It is important to note that the control groups consuming the low glycemic load Mediterranean diet achieved an excellent clinical response to the dietary intervention, but the inclusion of the specific phytochemical concen-trate targeting intercellular signal trans-duction pathways, in conjunction with the diet, produced statistically superior outcomes. Lerman et al, in a 2011 clinical intervention study, found that the Medi-terranean-style low glycemic load food plan improved the variables of metabolic syndrome in women, and the addition of a phytochemical-rich medical food en-hanced the benefits on lipoprotein bio-transformation.40
Based on a series of clinical intervention trials, Schiltz et al developed and pub-lished a food plan focused on phyto-chemical support of biotransformation/cellular signaling metabolic networks.41 In discussing the role of phytochemicals in this food plan, Minich and Bland reviewed the functions of specific dietary constitu-ents in supporting proper metabolic biotransformation and the correction of metabolic disturbances and concluded that specific phytochemically-rich foods can improve cellular signaling related to detoxification processes, inflammatory response and insulin sensitivity.42
Is there a “detoxification diet”?
The science that underlies clinical nutri-tion is undergoing a paradigm shift. The concept that specific phytochemicals can modulate intercellular signal transduc-tion processes that regulate genetic ex-pression of phase 1, 2, and 3 enzymes in-volved in the control of biotransformation
processes represents a very important ad-vance in understanding the role that diet and specific foods play in detoxification. These scientific advances, coupled with advances in the field of nutrigenomics, provide for a better appreciation of how to develop personalized nutritional in-tervention programs. While there is not a specific detoxification diet, there are principles relating certain foods and phy-tochemicals to the detoxification process, which can be used to develop personal-ized dietary intervention programs for people with disturbed metabolism asso-ciated with impaired biotransformation/detoxification. The take-away message emerging from the progress made in the fields of clinical nutrition, nutrigenomics and nutritoxigenomics over the past ten years is that food, dietary quality and the specific nutrient and phytonutrient signa-ture of the diet have an important impact on biotransformation/detoxification pro-cesses in humans.
Jeffrey S. Bland, Metagenics’ Chief Science Officer, and President of Metaproteomics, is an internationally recognized leader in the nutritional medicine field. Headquartered in Gig Harbor, WA, Dr. Bland founded Health-Comm International, Inc. in 1985, and served as its Chief Executive Officer until the merger with its strategic partner, Metagen-ics, in 2000. A nutritional biochemist and registered clinical laboratory director, Dr. Bland is a former professor of biochemistry at the University of Puget Sound, and a pre-vious Director of Nutritional Research at the Linus Pauling Institute of Science and Medi-cine. Dr. Bland has authored five books on nutritional medicine for the healthcare professional and five books on nutrition and health for the general public. He is the principal author of over 100 peer-reviewed research papers on nutritional biochem-istry. Contact Dr. Bland at 253-851-3943 / 800-843-9660 or Fax: 253-851-9749.
References
1. Nebert DW, Nelson DR, Adesnik M, et al. The P450 superfamily: updated listing of all genes and rec-ommended nomenclature for the chromosomal loci. DNA. 1989;8:1-13.
2. Nelson DR, Kamataki T, Waxman DJ, et al. The P450 superfamily: update on new sequences, gene
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mapping, accession numbers, early trivial names of enzymes, and nomenclature. DNA Cell Biol. 1993;12:1-51.
3. Ghose R, Guo T, Haque N. Regulation of gene ex-pression of hepatic drug metabolizing enzymes and transporters by the Toll-like receptor 2 ligand, lipoteichoic acid. Biochem Biophys. 2009;481:123-130.
4. Jana S, Paliwal J. Molecular mechanisms of cyto-chrome p450 induction: potential for drug-drug interactions. Curr Protein Pept Sci. 2007;8:619-628.
5. Bukvic N, Lovreglio P, Fanelli M, Susca FC, Ballini A, et al. Influence of some detoxification enzyme polymorphisms on cytogenetic biomarkers be-tween individuals exposed to very low doses of 1,3-butadiene. J Occup Environ Med. 2009;5:811-821.
6. Chen Q, Zhang T, Wang JF, Wei DQ. Advances in human cytochrome P450 and personalized medi-cine. Curr Drug Metab. 2011;12:436-444.
7. Snawder JE, Lipscomb JC. Interindividual vari-ance of cytochrome P450 forms in human hepatic microsomes: correlation of individual forms with xenobiotic metabolism and implications in risk assessment. Regul Toxicol Pharmacol. 2000;32:200-209.
8. Fimognari C, Lenzi M, Hrelia P. Interaction of the isothiocyanate sulforaphane with drug dispo-sition and metabolism: pharmacological and toxicological implications. Curr Drug Metab. 2008;9:668-678.
9. Lahoz A, Donato MT, Picazo L, GÛmez-LechÛn MJ, Castell JV. Determination of major human cyto-chrome P450s activities in 96-well plates using liq-uid chromatography tandem mass spectrometry. Toxicol In Vitro. 2007;21:1247-1252.
10. Yoo HD, Lee YB. Interplay of pharmacoge-netic variations in ABCB1 transporters and cytochrome P450 enzymes. Arch Pharm Res. 2011;34:1817-1828.
11. N Schiødt FV, Rochling FA, Casey DL, Lee WM. Acetaminophen toxicity in an urban county hos-pital. NEJM. 1997;337:1112-1117.
12. Pantuck EJ, Hsiao KC, Loub WD, et al. Stimula-tory effect of vegetables on intestinal drug metabolism in the rat. J Pharmacol Exp Ther. 1976;198:278-283.
13. Brodie MJ, Boobis AR, Toverud EL, et al. Drug me-tabolism in white vegetarians. Br J Clin Pharma-col. 1980;9:523-525.
14. Conney AH, Buening MK, Pantuck EJ, et al. Regu-lation of human drug metabolism by dietary fac-tors. Ciba Found Symp. 1980;76:147-167.
15. Pantuck EJ, Pantuck CB, Garland WA, et al. Stimu-latory effect of Brussels sprouts and cabbage on human drug metabolism. Clin Pharmacol Ther. 1979;25:88-95.
16. Abdull Razis AF, Bagatta M, De Nicola GR, Iori R, Ioannides C. Intact glucosinolates modulate he-patic cytochrome P450 and phase II conjugation activities and may contribute directly to the che-mopreventive activity of cruciferous vegetables. Toxicology. 2010 ;277:74-85.
17. Walter-Sack I, Klotz U. Influence of diet and nutri-tional status on drug metabolism. Clin Pharma-cokinet. 1996;31:47-64.
18. Pantuck EJ, Pantuck CB, Kappas A, Conney AH, Anderson KE. Effects of protein and carbohy-drate content of diet on drug conjugation. Clin Pharmacol Ther. 1991;50:254-258.
19. Minich DM, Bland JS. Acid-alkaline balance: role in chronic disease and detoxification. Altern Ther Health Med. 2007;13:62-65.
20. Villa-Cruz V, Davila J, Viana MT, Vazquez-Duhalt R. Effect of broccoli (Brassica oleracea) and its phytochemical sulforaphane in balanced diets on the detoxification enzymes levels of tilapia (Oreochromis niloticus) exposed to a carcino-genic and mutagenic pollutant. Chemosphere. 2009;74:1145-1151.
21. Konsue N, Ioannides C. Modulation of carcino-gen-metabolising cytochromes P450 in human liver by the chemopreventive phytochemical phenethyl isothiocyanate, a constituent of cru-ciferous vegetables. Toxicology. 2010;268:184-190.
22. Rabot S, Nugon-Baudon L, Szylit O. Alterations of the hepatic xenobiotic-metabolizing enzymes by a glucosinolate-rich diet in germ-free rats: in-fluence of a pre-induction with phenobarbital. Br J Nutr. 1993;70:347-354.
23. Singh A, Rao AR. Evaluation of the modulatory influence of food additive-garam masala on hepatic detoxication system. Indian J Exp Biol. 1992;30:1142-1145.
24. Nho CW, Jeffery E. The synergistic upregulation of phase II detoxification enzymes by glucosino-late breakdown products in cruciferous vegeta-bles. Toxicol Appl Pharmacol. 2001;174:146-152.
25. Hsieh TC, Lu X, Wang Z, Wu JM. Induction of qui-none reductase NQO1 by resveratrol in human K562 cells involves the antioxidant response ele-ment ARE and is accompanied by nuclear trans-location of transcription factor Nrf2. Med Chem. 2006;2:275-285.
26. Son TG, Camandola S, Mattson MP. Hormetic dietary phytochemicals. Neuromolecular Med. 2008;10:236-246.
27. Howitz KT, Sinclair DA. Xenohormesis: sens-ing the chemical cues of other species. Cell. 2008;133:387-391.
28. Minich DM, Lerman RH, Darland G, et al. Hop and acacia phytochemicals decreased lipotoxicity in 3T3-L1 adipocytes, db/db mice, and individuals with metabolic syndrome. J Nutr Metab. 2010; Epub 2010 May 18.
29. Babish JG, Pacioretty LM, Bland JS, et al. Antidia-betic screening of commercial botanical prod-ucts in 3T3-L1 adipocytes and db/db mice. J Med Food 2010;13:5355-5347.
What is a “Detoxification Diet?”
SAVE THE DATE!Saturday October 6, 2012Pre-FNCE DIFM Workshop
Integrative RD: Nutrition As Medicine, Confronting Cardio-Metabolic SyndromeCardiovascular disease and diabetes are twin epidemics with common roots in insulin resistance, obesity,
metabolic dysfunction and toxic overload. Nutrition interventions and lifestyle strategies are the most powerful tools available to confront this healthcare challenge. This workshop will teach practitioners to apply an integrative and functional approach to cardio-metabolic syndrome including an overview of core imbalances, nutrition physical
assessment, dietary supplements and functional laboratory testing. The concept of emotional brain training (EBT) to support behavior change, alleviate stress and promote well-being will be introduced. Case studies illustrating
application in clinical practice will be reviewed along with resources for further exploration.
Speakers: Kathie Madonna Swift, MS RD, Coco Newton, MS RD CCN, Mark Hyman, MD and Laurel Melin MA, RD
Look for more information in the Summer newsletters.
References continued on page 90
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What is a “Detoxification Diet”?
Circle the one best answer
1. Which of the following describes an example of how genetic polymorphism can affect xenobiotic metabolism?
a. Can determine the detoxification genotypes.
b. Can affect the speed of metabolism of specific substances.
c. Can predict the metabolites of first pass metabolism.
2. What role do the glucosinolates from cruciferous vegetables play in biotransformation?
a. Can modulate genetic expression of specific enzyme systems of both phase 1 and 2.
b. Delay the excretion of phase 3 compounds allowing enhanced detoxification.
c. Increase phase 1, first pass metabolism, while allowing phase 2 to remain constant.
3. Greater than expected cellular physiologic activity achieved at a low level of phytochemical intake is an example of which of the following?
a. Balanced detoxification
b. Xenohormesis
c. Yellow canary syndrome
4. Which of the following describes the phytochemical mechanism of action and its influence on detoxification?
a. Inhibition of specific nuclear transcription factors & de-activation of phases 2 & 3.
b. Induction of specific nuclear transcription factors & activation of phases 1, 2, & 3.
c. Deactivation of glucosinolate metabolites, which increases activation of phase 3.
5. Which of the following is an example of the scientific evidence for the use of phytochemicals in enhancing biotransformation processes?
a. Prevention of acetaminophen induced cellular injury & reduction of breast cancer risk.
b. Reversal of acetaminophen poisoning by IV infusion of cruciferous vegetable extracts.
c. In vivo studies demonstrating the prevention of HIV infection by stimulating CYP450.
What is a “Detoxification Diet?”
After reading this CPE article, the nutrition professional will be able to: 1. Describe how genetic polymorphisms can influence xenobiotic metabolism. 2. Identify the role glucosinolates from cruciferous vegetables play in biotransformation. 3. Define “xenohormesis.” 4. Describe the mechanism of action of phytochemicals and their influence on detoxification. 5. Discuss the scientific evidence for the use of phytochemicals in enhancing biotransformation processes. 6. Differentiate between the concept of a specific “detoxification diet” versus using what is known about
certain foods and phytonutrients to develop individualized diets to aid in the detoxification process.
What is a Detoxification Diet?Objectives
Answer Key: 1. b; 2. a; 3. b; 4. b; 5. a
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Hepatic Detoxification — An Overview
Shari Pollack, MPH, RD
Introduction
Among the liver’s many functions, de-
toxification has long been recognized as playing a vital role in maintaining good health and preventing disease. Whether the liver needs help to detoxify the on-slaught of toxic compounds it faces or is capable of handling the job unassisted is an area of intense debate within the medical community. Some argue that the growing toxic burden we face from environmental pollutants, coupled with the nutrient-poor standard American diet, places too great a stress on the liver. Therefore, detoxification support in the form of diet and nutrient supplementa-tion is needed to prevent the accumula-tion of toxins. Others argue that the body is well-equipped to handle the load and that attempting to assist in the detoxifica-tion process may cause more harm than good. A solid understanding of the he-patic detoxification system is necessary for one to appreciate the arguments on either side.
Biotransformation
The cell membrane is one of the body’s first lines of defense against foreign compounds, or xenobiotics. Its lipid bi-layer blocks entry of polar, or hydrophilic, compounds. Lipid-soluble compounds, on the other hand, diffuse across cell membranes with little difficulty. When hydrophobic xenobiotics, such as phar-maceutical and recreational drugs, food toxins, pesticides, and other environmen-tal pollutants find their way into the body, their non-polarity makes them difficult to excrete. The main task of hepatic detoxi-fication is to convert these lipid-soluble compounds into water-soluble metabo-lites that can be more easily excreted in the urine or bile. This conversion process, called biotransformation, is accomplished in two phases—functionalization and conjugation—first identified by RT Wil-liams in 1947.1
Phase 1
In phase 1, lipid-soluble compounds are converted into more polar compounds through chemical reactions that either add or expose a functional group, such as a hydroxyl group (-OH). Oxidation, re-duction, and hydrolysis are the main reac-tions in phase 1.2 In some cases, the result-ing metabolite may be excreted directly. More often, however, it requires further transformation by phase 2 enzymes.
The cytochrome P450 (CYP450) enzymes are responsible for catalyzing the major-ity of phase 1 reactions. This “superfam-ily of mixed function oxidases” is found throughout all biological kingdoms.2 Hu-mans have 57 different CYP450 genes.3 The CYP enzymes are found in the endo-plasmic reticulum (ER) and mitochondria, mainly in the liver, but also in the gastro-intestinal tract, kidneys, lungs, brain, and other tissues. They are hemoproteins with broad substrate specificity that act not only on xenobiotics, but also on endog-enous compounds such as fatty acids, cholesterol, steroid hormones, and eico-sanoids. With NADPH as a cofactor, they catalyze reactions that introduce one atom of oxygen into a substrate; as such, they are sometimes referred to as mono-oxygenases.
While the action of the CYPs 450 enzymes are generally thought of as detoxifying, phase 1 reactions can also produce inter-mediate compounds that are more toxic than the parent compounds; this is re-ferred to as bioactivation.2 These reactive metabolites, if not modified by phase 2 enzymes, are capable of interacting with cellular components, such as proteins, RNA and DNA, causing damage that “can lead to carcinogenicity, immunotoxicity, [and] necrosis.”4
Phase 2
Biotransformation continues in phase 2. The phase 2 enzymes catalyze reactions that add a polar group to the reactive site of the intermediate compounds produced by phase 1 reactions (though some toxins bypass phase 1 and are metabolized by phase 2 enzymes directly). The resulting
conjugates are water-soluble and can be excreted in the urine and bile. The six main reactions in phase 2 are glucuroni-dation, sulfation, acetylation, glutathione conjugation (with subsequent mercap-turic acid formation), amino acid conju-gation, and methylation.5 The co-factors, enzymes, and substrates associated with these reactions can be found in Table 1.
According to Jeffery (2007), some prod-ucts of glucuronidation are excreted via the bile but are then reabsorbed due to the action of a beta-glucuronidase in the gut microflora, which “can break the conjugate, reversing the hydrophilicity gained from conjugation.”2
Phase 3 — Antiporter Activity
The efflux proteins, such as p-glycopro-tein, multidrug resistance-associated pro-teins (MRPs), and breast cancer resistance protein (BCRP), along with solute carrier transporters, carry out phase 3 of detoxifi-cation.9 These ATP-binding cassette (ABC) transporters, or antiporters, are present in the apical membranes of enterocytes and hepatocytes and act as pumps, medi-ating both the uptake of toxins from the intestinal lumen and the excretion of me-tabolites into bile.10 As such, they play an important role, first in regulating the de-gree to which a given toxin is absorbed, and then in shuttling out of the liver the hydrophilic compounds resulting from phase 2 reactions.
Balancing Act
Age, sex, genetics, smoking status, preg-nancy, disease, environmental exposure, and diet can all impact the body’s abil-ity to metabolize xenobiotics.1,7,11 The en-zymes involved in both phase 1 and phase 2 reactions can be induced or inhibited by many factors. For example, some com-pounds will upregulate the production of particular enzymes required for their own biotransformation, thus increasing the rate of detoxification. Some may in-fluence a single enzyme or phase (mono-functional inducers), while others may induce multiple enzyme activities (multi-functional inducers).11 According to Liska (2005):
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Mono-functional inducers, such as poly-cyclic hydrocarbons from cigarette smoke and aryl amines from charbroiled meats, result in dramatic induction of the CY-P1A1 and CYP1A2 enzymes, leading to a substantial increase in Phase 1 activity, with little or no induction of phase 2 en-zymes...Induction of these activities with-out co-induction of Phase 2 activities may lead to an uncoupling of the Phase 1 and Phase 2 balance of activity and, therefore, a higher level of reactive intermediates, which can cause damage to DNA, RNA, and proteins.11
Likewise, induction of phase 1 by supple-mentation with nutrients that increase CYP450 activity, such as ascorbic acid, selenium, and polyphenols, without con-comitant support for phase 2 activity, could lead to cellular damage, as the high concentration of circulating reactive com-pounds exceeds the capacity of phase 2 pathways to detoxify them.
Inhibition of xenobiotic metabolism can result from the action of a single com-pound (for example, the flavanone nar-ingenin, found in grapefruit, which exerts
an inhibitory effect on CYP1A2) or mul-tiple compounds (as when two or more toxins compete for the same enzyme or enzymes). Insufficient intake of protein, fatty acids, phytonutrients, and micronu-trients involved as enzymatic cofactors can also decrease detoxification. Further-more, detoxification can be downregu-lated by the depletion of cofactors. For example, the generation of free radicals by phase 1 reactions can result in the de-pletion of glutathione, an important free radical scavenger/antioxidant, which in turn decreases phase 2 glutathione con-
Hepatic Detoxification — An Overview
Table 1: The Major Phase 2 Reactions
Reaction and Co-factor5,6 Enzymes6 Substrates5,7
Glucuronidation Glucuronosyltransferases Most prescription drugsconjugation with glucuronic acid Fat-soluble vitamins Steroid hormones Bilirubin Food additives/dietary toxins
Sulfation Sulphotransferases Certain drugs (acetaminophen, warfarin)conjugation with adenosine 3’-phosphate- Ethyl alcohol5’-phosphosulfate Melatonin Neurotransmitters Steroid hormones Thyroid hormones Food additives Intestinal bacterial toxins
Acetylation Acetyltransferases Dietary toxinsconjugation with acetyl-CoA Caffeine Histamine Serotonin B-complex vitamins
Glutathione Conjugation Glutathione S-transferases Aflatoxin (mold from Aspergillus flavis conjugation with reduced glutathione (GSH) on peanuts, for example) Bacterial toxins Bilirubin Ethyl alcohol metabolites Lipid peroxides Naphthalene (from plastics) Petrochemicals Prostaglandins Toxic metals
Amino Acid Conjugation Acyl-coenzyme A ligase Food preservativesconjugation with arginine, Acyl-CoA-amino-acid-N- Herbicidesglutamine, glycine, ornithine, or taurine acyltransferased Insecticides NSAIDs (Ibuprofen)d
Methylation Methyltransferases Drugsdonation of methyl groups from S- Estrogensadenosylmethionine (SAM) Vitamin B-12 Pesticides MercuryaSalguero5 cMurray7
bQueen6 dKnights8
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jugation activity.
Take Home Message
With 3.93 billion pounds of toxic chemi-cals released into the US environment, by the latest estimates,12 there can be little doubt that properly functioning detoxi-fication pathways are vital to defending the body against the associated health threats. Reducing one’s exposure to en-vironmental toxins, including food addi-tives and pesticide residues, minimizing intake of processed foods, and optimizing nutrient intake through a whole foods diet is a conservative and prudent ap-proach to handling the ever-increasing toxic burden with which we are faced. Due to individual variability in detoxifi-cation capacity related to factors such as genetics, lifestyle, drug intake, and other environmental exposures, this approach may not go far enough. Hepatic detoxi-fication involves a highly complex array of enzymes, cofactors, and reactions. Maintaining the proper balance between phase 1 and phase 2 activity is essential,
and attempts to support the detoxifica-tion process through diet or nutritional supplementation require a thorough un-derstanding of the complicated pathways involved.
Shari Pollack, MPH, RD is the Education and Staff Development Dietitian at the Jesse Brown VA Medical Center in Chicago and is the CPE Editor for the DIFM newsletter. She can be contacted at [email protected] or 312-569-6568.
References1. Liska D, Lyon M, Jones DS. Detoxification and bio-
transformational imbalances. In: Jones DS, Quinn S, eds. The Textbook of Functional Medicine. Gig Harbor, WA: The Institute for Functional Medicine; 2005: 275-298.
2. Jeffery EH. IFM symposium: detoxification basics. Altern Ther Health Med. 2007;13(2)(suppl):S96-S97.
3. Nelson DR, Nebert DW. Cytochrome P450 (CYP) gene superfamily. In: Encyclopedia of Life Sciences (ELS). Chicester, West Sussex: John Wiley & Sons, Ltd.; 2011. http://www.els.net/WileyCDA/ElsAr-ticle/refld-a0005667.html. Accessed January 2, 2012.
4. Ioannides C. Effect of diet and nutrition on ex-pression of cytochromes P450. Xenobiotica.
1999;29(2):109-154.
5. Salguero ML. Detoxification. In: Rakel D, ed. Inte-grative Medicine. 2nd ed. Philadelphia, PA: Saun-ders; 2007:1123-1135.
6. Murray RK. Metabolism of Xenobiotics. In: Murray RK, Granner DK, Mayes PA, Rodwell VW, eds. Harp-er’s Biochemistry. 24th ed. Stamford, CT: Appleton & Lange; 1996:750-756.
7. Queen HL. Detox essentials. Health Realities Jour-nal. 2004;20(3):1-12.
8. Knights, K. Amino acid conjugation: contribu-tion to the metabolism and toxicity of xenobiotic carboxylic acids. In: Daly A, ed. Drug Metaboliz-ing Enzymes: Fundamentals, Study Methods, Re-cent Advances and Clinical Significance. Henry Stewart Talks Web site. http://hstalks.com/lib.php?t=HST9.9_20_1_2&c=252. 2007. Accessed January 11, 2012.
9. Murakami T, Takano M. Intestinal efflux transport-ers and drug absorption. Expert Opin Drug Metab Toxicol. 2008;4(7):923-939.
10. Oude Elferink RP, de Waart R. Transporters in the intestine limiting drug and toxin absorption. J Physiol Biochem. 2007;63(1):75-81.
11. Liska DJ. The detoxification enzyme systems. Al-ternat Med Rev. 1998;3(3):187-198.
12. US Environmental Protection Agency. 2010 Toxins Release Inventory National Analysis Summary. Epa.gov Web site. http://www.epa.gov/tri/Nation-alAnalysis/index.htm. Accessed January 7, 2012.
Hepatic Detoxification — An Overview
Fig. 22.1 Liver detoxification pathways and supportive nutrients, Textbook of Functional Medicine, © 2005 Institute for Functional Medicine
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Hepatic Detoxification—An Overview
Choose the one best answer.
1. Which of the following is the general process by which the liver detoxifies xenobiotics?
a. Converting lipid-soluble compounds into excretable water-soluble metabolites.
b. Converting water-soluble compounds into excretable lipid-soluble metabolites.
c. Altering the lipid membrane creating tight junctions to prevent entry of foreign matter.
2. Which of the following describes bioactivation?
a. Formation of a less reactive/toxic product after phase 1 reaction.
b. Formation of a more reactive/toxic product after phase 1 reaction.
c. Formation of a neutral compound after phase 2 reaction.
3. Which of the following best describes biotransformation?
a. Conversion process relying largely on oxidases, glucosinolases and ligases.
b. Conversion process that results in a hydrophobic metabolite post phase 2.
c. Conversion process relying largely on CYP450 enzymes and conjugation OR Conversion process accomplished via functionalization and conjugation.
4. Which of the following is the main outcome of phase 1 reaction?
a. Hydroxylated or more polar compound.
b. Hydroxylated or more hydrophobic compound.
c. Lipid peroxidation to a neutral compound.
5. Which is the primary family of enzymes involved in phase 1 detoxification?
a. Mixed function oxidases; CYM 450.
b. Mixed function oxidases; CYG 450.
c. Mixed function oxidases; CYP 450.
6. Which four types of conjugation reactions are involved in phase 2 detoxification?
a. Peroxidation, sulfation, acetylation and glutathione conjugation.
b. Amino acid conjugation, methylation, glucuronidation and sulfation.
c. Sulfation, hydroxylation, acetylation, and glucuronidation.
7. Which of the following is a role of the phase 3 efflux proteins?
a. Mediating uptake of intestinal toxins & excretion of the conjugated compound.
b. Inducing the activity of CYP1A1 enzymes and inhibiting CYP1A2 enzymes.
c. Re-establishing the lipid bilayer of the cell membrane after phase 1 reactions.
Hepatic Detoxification — An Overview
Answer Key: 1. a; 2. b; 3. c; 4. a; 5. c; 6. b; 7. aHepatic Detoxification—An OverviewObjectives
After reading this CPE article, the nutrition professional will be able to: 7. Describe the general process by which the liver detoxifies xenobiotics. 8. Differentiate between biotransformation and bioactivation. 9. Identify the main outcome of phase 1 reactions. 10. Identify the primary family of enzymes involved in phase 1 detoxification. 11. Identify at least 4 types of conjugation reactions involved in phase 2 detoxification. 12. Understand possible reasons for and consequences of an imbalance between phase 1 and phase 2
reactions. 13. Understand the role of the phase 3 efflux proteins.
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CPE Objectives and Questions
CPE Reporting Form • Spring 2012 • Detoxification. Expiration Date May 31, 2013
Please print or type
Name: ______________________________________________________________________________________________
Address: ____________________________________________________________________________________________
Academy Membership #: __________________________________Phone: ______________________________________
Email Address: _______________________________________________________________________________________
DIFM Member Yes No Date Test Completed: ____/____/____ This activity has been approved for three hours of CPE credit. You will be notified if hours are not approved.Possible Learning Codes: 2000, 2010, 2020, 2080, 2100, 4000, Level 2.
1) Read both Continuing Professional Education articles and answer the associated quiz questions. For each question, select the one best response. Compare your answers to the answer keys pages 72 and 76.
2) Send your completed quiz and application for CPE credit by email, fax, or mail to:
Shari Pollack, MPH, RD4500 Keeney Street, Skokie, IL [email protected]: 312-569-6118
3) Complete the CPE Certificate on page 78 and retain it for your records. You will be notified only if your application for credit is not approved.
Instructions for Completing the CPE Activity for Credit
CPE answer sheet for questions for Spring 2012 CPE and reporting instructions: Detoxification
These articles are approved for 3.0 hours of continuing professional education by the Commission on Dietetic Registration. Possible Learning Codes: 2000, 2010, 2020, 4000, 4040, Level 2.
1. a; b; c2. a; b; c3. a; b; c
4. a; b; c5. a; b; c
1. a; b; c 2. a; b; c3. a; b; c
4. a; b; c5. a; b; c6. a; b; c7. a; b; c
What is a “Detoxification Diet”? Hepatic Detoxification—an Overview
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CPE CERTIFICATE
CPEUs AwardedCPEUs Awarded
COPY I: ATTENDEE VEFICATIONPlease obtain a separate Attendance Form for license verification and your own records. You should record each session on your Learning Activities Log (Step 4), and retain a completed form for your file in the event you are audited by CDR.
Continuing Professional Education Certificate of Attendance American Dietetic Association – DPG/MIG
COPY II: STATE LICENSURE VERIFICATION Please complete a separate Certificate of Attendance Form for each session attended. Present a completed form to your state Licensure Board upon request.
Continuing Professional Education Certificate of Attendance American Dietetic Association – DPG/MIG
CDR Accredited Provider Signature RETAIN ORIGINAL COPY FOR YOUR RECORDS
CPE Level
Date(s) Completed
Title of Program
Date(s) Completed
Title of the Program
Participant Name
RD/DTR ID Number
CPEUs Awarded
CDR Accredited Provider # AM003
CDR Accredited Provider # AM003
Participant Name
RD/DTR ID Number
CPE Level Learning Need Code(s)
Learning Need Code(s)
CDR Accredited Provider Signature STATE COPY
Sarah Harding Laidlaw, MS RD CDE
Sarah Harding Laidlaw, MS RD CDE
Academy of Nutrition and Dietetics
Academy of Nutrition and Dietetics
Spring 2012 Volume 14, Issue 4www.integrativeRD.org
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By Kathie Madonna Swift MS, RD, LDN
Detox diets are born, bred and branded at break-
neck speed. There is no doubt that “detox” is a hot
topic for consumers searching for natural ways to ward off disease, manage body burden, achieve healthy weight, and treat inflammatory conditions. A dietitian trained in integrative and functional med-icine can guide an individual interested in “detoxing” and advance their client’s un-derstanding of this sophisticated physi-ological process that is highly dependent on optimal nutrition.
Here are a few key steps that outline how to apply evidence-based research to sup-port detoxification:
1. Use the Integrative and Functional Medical Nutrition Therapy (IFMNT) Radial1 as a “detox map.” This outlines the critical factors to consider in an in-tegrative and functional nutrition “de-tox” care plan including:
a. Genetics. There are certain genetic tendencies or “SNPs” (single nucleo-tide polymorphisms) that influence detoxification, such as GSTM, MTH-FR, COMT, SOD, etc. If you do not have SNP data, investigate your cli-ent’s family history and consider the possibilities that may lie within the family DNA and the individual’s en-vironment that could be interacting with their “book of life.”
b. Triggers. P.A.I.N.T.S. is a heuristic2 that encompasses essential detox data to gather: P=pathogens, A=allergens, I=intolerances, N=nutritional imbal-ances, T= Toxins and S=Stress. In-corporate a thorough environmental history as a part of your nutrition as-sessment that investigates P.A.I.N.T.S.
c. Lifestyle. Tune into clues in the pa-tient’s story or medical history that are especially relevant to detoxification (e.g. mold exposure, toxic food load, sleep deprivation, emotional trau-ma, medications, supplements, etc.).
d. Core Imbalances. A holistic ap-proach to detoxification appreciates that it is not a stand-alone process but is highly integrated and influ-enced by cellular integrity, energy metabolism, digestive processes, neuro-endocrine-immune function, oxidative stress and nutritional sta-tus.
e. System, Signs & Symptoms. A nutrition-fo-cused physical can provide fur-ther evidence about detoxi-fication func-tion. A medical symptom ques-tionnaire (MSQ) is a useful tool that provides i n f o r m a t i o n about physical symptoms rel-evant to de-toxification, in-cluding fatigue, brain fog, fluid retention, elimination problems, etc.
f. Biomarkers. Conventional labs should include basic biomarkers such as C-reactive protein, MTHFR, serum homocysteine, liver enzymes including GGT (marker of potential toxic burden), A1C, and nutrient lev-els including serum 25-OH vitamin D, B vitamins, magnesium and zinc. There are a number of functional di-agnostics that expand the biochemi-cal data, such as urine organic acids, urine toxic elements (heavy metals) and detoxigenomics profiles.
g. Metabolic Pathways/Networks. An understanding of the liver detoxifi-cation pathways (Phase 1, 2 & 3) and their interconnectedness to other biological processes is essential. The liver, aptly dubbed the workhorse organ of detoxification, should be viewed in the context of a “whole systems” approach to health and healing. Connecting the dots of de-
tox data together requires a compre-hension of physiological networks beyond our working knowledge of the infamous Kreb’s cycle.
2. Begin with food. As simple as it sounds, a “foods first” approach is the ideal way to support detoxification in-
cluding these key strategies:
a. Optimize calories and macronu-trients to support detox. The de-toxification pathways are dependent on fuel in the form of high quality, nutrient dense whole foods. Short-changing the system of an optimal amount of calories, as often promot-ed in popularized fasts or cleanses, may impair both phase 1 & 2 de-toxification. However, there is some research on water and juice fasting protocols that warrant our contin-ued attention.
b. Eliminate toxic ingredients and harmful cooking methods. There are numerous chemicals in the food supply (e.g. BPA, organochlorine compounds, parabens, etc.) that increase body burden and disrupt the endocrine system. Advise your clients of the sources of these toxins and identify cookware and cook-ing methods that are safe to use. A valuable resource for environmental
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Detoxification in Practice
Following is a brief description of each of the five key factors affecting heath, as depicted
by the IFMNT Radial. This information will be helpful in understanding the main
components of the Radial, and the interplay between these elements.
Lifestyle: Health promoting lifestyle factors can significantly decrease total body burden,
which can reduce the risk of chronic disease development and progression. “Food as
medicine” and the twin partnership of nutritional science [or nutritional biology?] and the
art of nourishment are cardinal tenets of the Radial’s lifestyle sphere. A whole-foods,
plant-centered diet that embraces one’s unique biochemistry, culture and traditions
provides the foundation for optimal health. Other lifestyle pillars of health include
movement/physical activity, restorative sleep, stress resiliency, mindfulness, spiritual
practices, and connection to nature and community. All of these lifestyle factors
contribute to a nutrition care process that is personalized, meaningful and transformative.
Systems, Signs & Symptoms: Nutritional systems biology makes the connection of
physical signs and symptoms to body systems and how they interact with each other and
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health information is www.ewg.org.
c. Remove food allergens and intol-erances. Adverse food reactions, including both food allergens (e.g. egg, shellfish, etc.) and intolerances (gluten, dairy, fructose, etc.) contrib-ute to a host of systemic disruptions. Compromised intestinal permeabil-ity, also known as “leaky gut,” impairs detoxification capacity.
d. Focus on fiber and fluids. Fiber is a matrix that has multiple functions and is essential for digestive health. Adequate fluids partnered with fi-ber aids in elimination, an important exit route for toxins. Fiber also nour-ishes the gut flora, resident bugs that communicate with the immune sys-tem and influence the second brain (gut brain).
e. Boost antioxidant and micronutri-ent defense. Endogenously derived metabolic toxins, such as advanced glycation end products (AGEs), lipid peroxides, and uric acid are often the result of a nutritionally challenged/
Standard American diet (SAD). Cleaning up the diet by eliminating refined and processed foods, un-healthy fats, excess animal protein and other adulterations is one of the most significant changes that can promote healthy detoxification.
f. Include the Detoxicants. A squad of nutrients, dubbed “detoxicants,” provides the co-factors necessary to drive the detoxification process. A colorful, plant-centric plate should include: dark greens (dandelion, spinach, broccoli raab, etc.); yellow orange (sweet potatoes, carrots, peaches, etc.); red/pink (grapefruit, radiccio, vine-ripened tomatoes, etc.); white/green (garlic, onions, fen-nel, etc.); blue/purple (blueberries, blackberries, eggplant, etc.), along with the phytonutrients found in herbs and spices (turmeric, ginger, rosemary, etc.). By diversifying plant foods in the diet, the messages found in the phytoDNA are transcribed to the benefit of the host.
3. Supplement strategically. A person-alized supplement program may be designed based on the data analyzed and synthesized from a comprehensive nutrition assessment using the IFMNT Radial map. Medical foods, amino ac-ids, B vitamins, omega-3 fatty acids, and digestive products are commonly used supplements in a detoxification program and, if used, must be tailored to the individual’s unique needs.
4. Integrate complementary healing modalities. Body, mind and spirit should be integrated in a natural de-toxification program. Meditation, mindfulness, movement, tai chi, chi gong, guided imagery, prayer and oth-er modalities can be transformative ex-periences in a healing journey.
5. Explore more about detox. There are a number of resources for the Integra-tive RD interested in detoxification. One of my favorite books is Detoxifi-cation and Healing: The Key to Optimal Health by functional medicine expert, Dr. Sydney Baker. The archived Integra-
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Detoxification in Practice
Detox Sample Menu*Breakfast Smoothie: Dark greens, organic apple, fresh ginger, pumpkin seed protein powder, coconut milk
Snack: Pink grapefruit slices
Lunch: Wild salmon (grilled or canned) with parsley pesto, sweet potato, curried cauliflower
Snack: Avocado slices with a splash of lime
Dinner: White Bean Minestrone Soup, radicchio, fennel & arugula salad with extra-virgin olive oil and lemon vinaigrette
* Dairy, Grain, Soy, Nut, Shellfish free
White Bean Minestrone SoupPrep Time: 20 min Cook Time: 40 min Makes: 6 (1 ½ cups) Servings6 cups low-sodium, gluten-free vegetable broth (or The Inside Tract Vegetable Broth)2 carrots, peeled and cut into 1⁄2”-thick rounds2 ribs celery, cut into 1⁄2” pieces1 cup baby portobello mushrooms, quartered3 small zucchini, halved lengthwise, cut into 1⁄2” pieces1 can (15 ounces) cannellini beans, drained1 can (141⁄2 ounces) chopped tomatoes1 teaspoon dried basil1 teaspoon crushed dried rosemarySea salt to tasteFreshly ground black pepper to taste2 cups chopped escaroleFresh basilAdd all the ingredients except the escarole to a 6- to 8-quart pot. Increase the heat to high and bring the soup to a boil. Reduce the heat to medium-low, partially cover the pot and simmer for 30 minutes. Stir in the escarole and simmer 5 minutes longer. Sprinkle with fresh basil and ladle the soup into 6 bowls.(Used with permission from The Inside Tract: Your Good Gut Guide to Great Digestive Health, Rodale 2011)
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tiveRD webinar on Persistent Organic Pollutants by Dr. Elizabeth Redmond is loaded with clinical pearls on detoxifi-cation. You can also purchase the Pre-FNCE CD, Achieving Hormone Balance: An Endocrine Dance of Environment, Genes, Diet and Detoxification from www.IntegatriveRD.org. And if you are up for a detox retreat, join me and my esteemed colleagues in the beautiful Berkshires in Massachusetts, for a five-day CPEU program on natural detoxi-
fication at Kripalu Center for Yoga and Health (www.kripalu.org).
Kathie Madonna Swift, MS, RD, LDN is the founder of SwiftNutrition (www.swiftnutrition.com) and author with Dr. Gerard Mullin of The Inside Tract: Your Good Gut Guide to Great Digestive Health (Rodale, 2011). Kathie leads Healthy Living Immersion programs at Kripalu Center for Yoga and Health, Stockbridge MA. Detoxification in Practice is an excerpt from
Natural Detoxification in her upcoming “SwiftNutrition” ebook series.
References1. Ford D, Raj S, Batheja RK, DeBusk R, Grotto D, et al.
American Dietetic Association: Standards of Prac-tice and Standards of Professional Performance for Registered Dietitians (Competent, Proficient, and Expert) in Integrative and Functional Medi-cine. J ADA.111: 902-913.e23, June 2011. Accessed 4/14/2012
2. Food As Medicine, Center for Mind Body Medi-cine, 2008.
Detoxification in Practice
Philadelphia will play host to this year’s Food & Nutrition Conference & Expo where you can discover new trends, exciting research and new products all under one roof.
Don’t miss out on:
• Career-enhancing educational sessions focusing on what you need to know including social media, technology and leadership.
• Inspirational keynote speaker messages of courage, strength, leadership and, above all, perseverance.
• Your chance to earn a minimum of 20.5 CPE hours.
Earn CPE, make connections and discover innovation @ FNCE.
Ethan A. Bergman, PhD, RD, CD, FADAAcademy President • 2012-2013
Join Me
This is just a sampling of what FNCE 2012 will offer. Visit us at www.eatright.org/fnce for the whole story.
Registration opens June 1.
New name, a new look is coming. The DIFM newsletter name has changed to
THE INTEGRATIVE RD and the look will be changing soon.
Spring 2012 Volume 14, Issue 4www.integrativeRD.org
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Beth Ellen DiLuglio, MS, RD, CCN, LD/N
Metabolic Detoxifi-cation, Toxins, and Nutritional Require-ments
We generate and are exposed to compounds that are potentially harmful to our health. These com-
pounds must be broken down and elimi-nated from the body to minimize negative health effects. Xenobiotics such as pesti-cides, herbicides, fungicides, plastic-based endocrine disruptors (phthalates, Bisphe-nol A, etc.), toxic heavy metals (cadmium, lead, mercury, arsenic, etc.), industrial chemicals (PCBs, PBBs, solvents, styrenes, etc.), and medications can disrupt metabo-lism and damage cells if not defused and removed.1-3 Even endogenously generated hormones, including estrogen and epi-nephrine, must be metabolized and elimi-nated properly. Even at low levels, chronic exposure to and bioaccumulation of toxins and metabolites can alter metabolism and disrupt homeostasis. Such disruptions can negatively affect endocrine, nervous, and immune systems and may contribute to Parkinson’s, Alzheimer’s and autoimmune diseases (e.g. systemic lupus erythemato-sus and scleroderma), allergies, cognitive deficits and mood changes, glucose dys-regulation, and cancer.1-4
We must detoxify or “biotransform” these harmful elements into compounds that can be more easily excreted. The process primarily involves conversion of a fat-solu-ble toxin into a less harmful, water-soluble compound that can be excreted via urine or sweat. There are two main phases of detox-ification, with an intermediary phase dur-ing which molecules with greater toxicity can be generated. Balance between phase I and phase II, as well as ample antioxidant protection during the intermediary phase, is essential for safe and effective detoxi-fication. Upregulation of phase I without adequate completion of phase II can ulti-mately increase toxic burden and disrupt
metabolism. Excretion of biotransformed toxins—via urine, feces, and sweat—is also a crucial step in the process. Saunas may be instrumental in this process by facilitating the mobilization and excretion of stored toxins.5 Some toxins may require chelating or “binding” and can be excreted in the bile and feces. If toxins are not completely de-toxified and excreted, they can accumulate in the liver or get packaged and shipped out for storage in adipose tissue—virtu-ally a “toxic waste dump.” This vital task of detoxification depends on total exposure and body burden, nutritional status, and genetic competence. A system that is over-loaded with toxins and undersupplied with nutrient cofactors may eventually reach TILT (Toxin Induced Loss of Tolerance) and detoxification is no longer adequate or ef-fective. Functional deterioration quickly ensues and signs and symptoms of disease prevail. For a case-based overview of the many facets of detoxification, see Detoxify for Life: How Toxins are Robbing You of Your Health and What You Can Do About It by Dr. John C. Cline, a physician specializing in the treatment of chronic and complex ill-nesses.6
A person’s genetic makeup and degree of exposure also factor into the detoxifica-tion equation. Some individuals may have a SNP (single nucleotide polymorphism) that compromises detoxification capa-bilities because of altered or inadequate production of the enzymes and cofactors.7 Bioaccumulation and exposure during critical periods of development must also be taken into account. Toxins become con-centrated at the top of the food chain and in areas of greater contamination. Prenatal exposure to toxins also must be taken into account considering that an average of 200 chemicals have been measured in the cord blood of newborns—indicative of what the mother was exposed to and stored her-self.8-11 We may be able to reduce our ex-posure to toxins by increasing awareness of their sources, especially pesticides com-monly used in food production. The Envi-ronmental Working Group has compiled a user-friendly list of “The Dirty Dozen” and
“The Clean 15” (a downloadable PDF) that ranks fresh produce by its content and ac-cumulation of pesticides.12
All phases of detoxification rely heavily on a host of nutrients and phytonutrients for completion. The process is energy-dependent as well. Phase I (via oxidation, reduction, hydrolysis, hydration, or deha-logenation) utilizes B-complex vitamins, glutathione, branched-chain amino acids, flavonoids, and phospholipids. Phase II (via sulfation, glucuronidation, glutathione conjugation, acetylation, amino acid con-jugation, or methylation) employs glycine, taurine, glutamine, N-acetylcysteine, cys-teine, methionine, and methyl donors. The volatile intermediary phase is tempered by ascorbic acid, tocopherols, selenium, cop-per, zinc, manganese, CoQ10, thiols (from garlic, onions, and cruciferous vegeta-bles—broccoli, Brussels sprouts, cauliflow-er, watercress and cabbage), bioflavonoids, silymarin, and pycnogenol.3,13,14
Functional Laboratory Assessment
Comprehensive laboratory assessment of detoxification should address current nu-tritional status, actual toxic load, genetic polymorphisms, and detoxification compe-tence. A basic nutrition assessment should include review of an individual’s dietary intake, supplement plan, possible toxic ex-posures and triggers, physical evaluation of nutrient deficiencies, potential drug-in-duced nutrient depletions, complete meta-bolic panel (including RBC magnesium and 25-OH vitamin D) and a CBC with differen-tial. Though the majority of detoxification activity takes place in the liver, traditional “liver function” tests measuring AST, ALT, and GGPT tell us about liver pathology, not actual metabolic function or detoxification capacity.3 The gastrointestinal tract plays a role in detoxification and elimination of toxins and byproducts as well.
Specific lab tests are needed to assess an individual’s actual detoxification activity, capacity, and genetic competence. Serum, urine, saliva, and hair tests help identify toxic load and detoxification capacity. Ge-netic tests are available to identify SNPs
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for the enzymes involved in detoxification, including N-Acetyltransferase and gluta-thione S-transferase M1 and T1. SNPs in folate metabolism and DNA repair are also important in assessing clinical picture and disease risk.7 A functional evaluation of mi-cronutrient status is also recommended, which enables us to look beyond serum levels and assess what is available at the cellular level. Spectracell Laboratories, Inc. assesses micronutrient status by using depletion and repletion studies in white blood cells.15
Assessment of Phase I
Phase I detoxification of xenobiotics is car-ried out primarily by the cytochrome P450 (CYP) enzymes, a family of mixed function oxidases active in gastrointestinal wall cells, kidneys, lung, brain and, most abun-dantly, in the liver. Several compounds can influence and regulate CYP enzymes, including transcriptional factors such as NF-kappaB16,17 and nutritional compounds such as vitamins and minerals. Table 1 lists nutritional influences on CYP enzymes. However, one need note that caution must be used in extrapolating these animal re-sults to humans and that “many studies with individual nutrients were done sev-eral years ago and the indexes that were measured were often not very specific for particular P450 enzymes.18 The CYP en-zymes are believed to be “distinct gene products” and SNPs that affect their func-tion now can be easily identified. Current CYP activity can be assessed through “chal-lenge testing” using a “probe substance” with subsequent measurement of metabo-lites in urine, blood, or saliva.
Activity of the phase I cytochrome P450 enzyme CYP1A2 can be assessed using a caffeine challenge. CYPA12 is instrumental in detoxifying several substances including polyaromatic hydrocarbons and amines (found in pesticides and charbroiled meat, respectively), as well as a number of the carcinogens generated from cigarette smoke. Several factors can influence an individual’s CYPA12 activity, including al-cohol intake, toxin exposure, medication ingestion, nutritional status, and genetic factors.3 Following caffeine ingestion, two
to three saliva samples are obtained. The amount of caffeine and timing of sample acquisition are determined prior to test ad-ministration. Caffeine clearance can then be measured in the saliva.
Assessment of Phase II
Phase II conjugation combines a toxin or activated metabolite with an endogenous substrate (glucuronic acid, sulfate, glu-tathione, a methyl or acetyl group, or an amino acid) to produce a water-soluble compound that is more easily excreted.3 Defects in any of these steps can lead to suboptimal detoxification and metabolic abnormalities.
Phase II detoxification can best be evalu-ated by assessing amino acid and glu-tathione conjugation, glucuronidation, and sulfation. Using acetaminophen as a probe substance, normal detoxification via phase II sulfation (to form acetamino-phen sulfate), or glucuronidation (to form acetaminophen glucuronide) can be as-sessed. If metabolic cofactors are absent or inadequate, or if associated SNPs are present, acetaminophen will undergo a phase I biotransformation first, followed by glutathione conjugation, which will yield acetaminophen mercapturate. N-ace-tyl-p-benzoquinoneimine (NAPQI)—the highly reactive intermediary compound produced from this alternative metabolic pathway— is highly toxic to the liver and must be cleared quickly. NAPQI can easily accumulate if phase I activity is induced without a balance of phase II glutathione conjugation. It is for this reason that high doses of the glutathione precursor N-acetyl-cysteine (NAC) are used as a rescue treatment to detoxify NAPQI in the event of acetaminophen overdose.3
Phase II amino acid conjugation may utilize a variety of amino acids including glycine, arginine, taurine, and ornithine. Because glycine conjugation is a major pathway in humans, its assessment can be useful in evaluating amino acid conjugation over-all. Aspirin or sodium benzoate can be utilized as a probe substance for assessing this common pathway. Because aspirin is degraded to salicylic acid, measurement
of salicyluric acid (the major metabolite) in the urine can assess the competence of glycine conjugation. The minor metabolite salicyl glucuronide can be measured in the urine as well. If an individual is sensi-tive to salicylates, sodium benzoate can be used to assess phase II glycine conjugation. Evaluation of any of these detoxification pathways should be preceded by a 24 hour or more elimination of aspirin, acetamino-phen, foods that contain salicylates and/or sodium benzoate.19
Assessment of Antioxidant Status
Antioxidant intake and status can be as-sessed by a thorough nutrition intake eval-uation, as well as cell-based assessment of antioxidant status. Spectracell Laboratories provides analysis of lipoic acid, CoQ10, cys-teine, glutathione, selenium, vitamin E, and a SPECTROX™ evaluation of total antioxi-dant function as part of their micronutrient testing. Several other nutrients are evalu-ated as well.15
Heavy Metal Burden
The most common toxic elements tested are mercury, lead, arsenic, cadmium, alu-minum, and nickel. The CDC’s Agency of Toxic Substance and Disease Registry dis-cusses individual toxins, http://www.atsdr.cdc.gov/toxfaqs/index.asp. Evaluation of a heavy metal burden can be accomplished by using a variety of tests, including blood, urine (both provocative and not), fecal, and hair analysis.3 Traditionally, urine levels of heavy metals are only measured following administration of a flushing agent such as DMSA (dimercaptosuccinic acid), which mobilizes toxins from storage. Clinicians are now recommending testing a random serum sample prior to administration of the flushing agent in order to measure cir-culating toxins, especially cadmium. Pre-flush samples may also assist in determin-ing which chelating agent is best for the individual. Samples taken after the flushing agent has been administered will reflect total body burden.20-22
Laboratory Testing
The Institute of Functional Medicine (IFM) offers a plethora of user-friendly tools, as-
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sessment forms, and educational materials, many that address detoxification. Guide-lines and questionnaires are provided for addressing toxic exposure, functional labo-ratory testing, toxic metal provocation test-ing (to be administered by a physician), and components of a nutrition physical exam.23 In-depth education tools, programs, and updates are readily available as well. The IFM recommends the tests included in the Laboratory Testing Handout following this article for assessing detoxification and bio-transformation.
There are a number of laboratories that conduct the tests listed. Some can be or-dered by the patients themselves through websites such as DirectLabs.com, while
others must be ordered through a profes-sional account with the specific lab. Some tests must be administered by a physician. Sample lab reports from several of these tests can be viewed online via their respec-tive websites. The following are examples of laboratories and tests available at the time of this writing; information listed is di-rectly from the respective websites and full descriptions are available online.
Doctor’s Data (www.doctorsdata.com) Direct Labs (www.directlabs.com) Genova Diagnostics® (www.gdx.net)Metametrix (www.Metametrix.com)Spectracell Laboratories Micronutrient Testing (www.spectracell.com)Author’s notes: I have had personal com-
munication with functional medicine physicians and practitioners (MD, DO, ND, ARNP, RD, CCN, etc.) and have received and provided continuing education on the topic of laboratory assessment of detoxifi-cation, including recommendations to use the laboratories listed above. Once practi-tioners study and recognize the roles that xenobiotics, detoxification, nutrigenomics, and nutritional status play in both health and disease, evaluation of detoxification capacity will become mainstream.
Disclosure:
The author does maintain professional ac-counts with Directlabs, Metametrix, and Spectracell, but does not receive financial or other compensation.
Nutritional status Effect on index measuredVitamin A deficiency Decrease in P450 (total); decrease in oxidations of aminopyrine, ethylmorphine, aniline, benzo[a]pyrene, and 7-ethoxycoumarin Vitamin A, high concentration Increase in oxidations of aniline and 7-ethoxycourmarin Niacin deficiency Decrease in metabolism of anesthetics Riboflavin deficiency Mild Decrease in NADPH-P450 reductase; increase in oxidations of N-nitroso dimethylamine, aniline, and aminopyrineSevere Decrease in oxidations of benzo[a]pyrene, aminopyrine, ethylmorphine, N methylaniline, aniline, and acetanilidePyridoxine deficiency No effect in several mixed-function oxidases Thiamine deficiency Increase in P450 2E1, NADPH-P450, reductase, and cytochrome b5; decrease in oxidations of N-nitrosodimethylamine, acetaminophen, aniline, aminopyrine, ethylmorphine, zoxazolamine, and benzo[a]pyreneVitamin C deficiency Decrease in P450, NADPH-P450 reductase, and several mono-oxygenation activitiesVitamin C, high concentration Decrease in several monooxygenation activitiesVitamin E deficiency Decrease in oxidations of codeine, ethylmorphine, and benzo[a]pyreneFolic acid deficiency Decrease in induction of P450 2B1 by barbiturates Iron deficiency Decrease in oxidations of hexobarbital and aminopyrine; increase in oxidation of anilinIron, high concentration Increase in NADPH-dependent lipid peroxidationCopper deficiency Decrease in oxidations of aniline and hexobarbital; increase in oxidation of benzo[a]pyreneZinc deficiency Decrease in oxidations of pentobarbital and aminopyrine Calcium deficiency Decrease in several monooxygenation activities Magnesium deficiency Decrease in several monooxygenation activities Selenium deficiency Decrease in induction of P450 by phenobarbital Aluminum, high concentration Decrease in hepatic P450 oxidations of p-nitrophenetole and ethylmorphine Calcium, cobalt, other heavy metals, high concentration Decrease in P450 and related activities Iodide deficiency Increase in several monooxygenation activities
Guengerich FP. Influence of nutrients and other dietary materials on cytochrome P-450 enzymes. Am J Clin Nutr. 1995 Mar;61(3 Suppl):651S-658S. Review. © Used with permission.
TABLE 1 Effect of micronutrients on activities in animals linked to cytochrome P450 (CYP450)
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Beth Ellen DiLuglio is a Certified Clinical Nu-tritionist and Registered Dietitian. She has taught Elements of Nutrition at Palm Beach State College for over a decade, as well as a wide range of continuing education courses focused on nutrition for health professionals. Contact Beth at [email protected] or 561.881.9999.
References:1. Gaby AR. Nutritional Medicine. Concord, NH: Fritz
Perlberg Publishing; 2011.
2. Colborn T, vom Saal FS, Soto AM. Developmental ef-fects of endocrine-disrupting chemicals in wildlife and humans. Environ Health Perspect. 1993;101:378-84.
3. Alexander BJ, Ames BN, Baker SM, et al. Textbook of Functional Medicine, The Institute for Functional Medicine: Gig Harbor, WA, 2010.
4. Crinnion WJ. Environmental medicine, part one: the human burden of environmental toxins and their common health effects. Altern Med Rev. 2000;5:52-63.
5. Crinnion WJ. Sauna as a valuable clinical tool for cardiovascular, autoimmune, toxicant-induced and other chronic health problems. Altern Med Rev. 2011;16:215-25.
6. Cline JC, Grant P. Detoxify for Life: How Toxins are Robbing You of Your Health and What You Can Do About It. Stockton, CA: More Heart Than Talent Pub-lishing, Inc. 2008 http://detoxifyforlife.com/. Ac-cessed 3/11/2012.
7. Norppa H. Cytogenetic biomarkers and genetic polymorphisms. Toxicol Lett. 2004;149(1-3):309-34.
8. Genuis SJ. Nowhere to hide: Chemical toxicants and the unborn child. Reprod Toxicol. 2009;28(1):115-6.
9. EWG. Pollutants in Cord Blood. http://www.ewg.org/reports/bodyburden2/execsumm.php.Accessed 3/11/2012.
10. CDC. http://www.cdc.gov/exposurereport/execu-tive_summary.html. Accessed 3/11/2012.
11. Crinnion WJ. The CDC fourth national report on human exposure to environmental chemicals: what it tells us about our toxic burden and how it assists environmental medicine physicians. Altern Med Rev. 2010;15:101-9.
12. EWG. Shopper’s Guide to Pesticides in Produce. http://www.ewg.org/foodnews/. Accessed 3/11/2012.
13. Percival M. Phytonutrients and detoxification. Clin-ical Nutrition Insights. 1997;5:1-4.
14. Lhoste EF, Gloux K, De Waziers I, et al. The activities of several detoxication enzymes are differentially
induced by juices of garden cress, water cress and mustard in human HepG2 cells. Chem Biol Interact. 2004;150(3):211-9.
15. Spectracell Laboratories. http://www.spectracell.com/mnt/. Accessed 3/12/2012.
16. Zordoky BN, El-Kadi AO. Role of NF-kappaB in the regulation of cytochrome P450 enzymes. Curr Drug Metab. 2009;10:164-78.
17. Guengerich FP. Characterization of human cyto-chrome P450 enzymes. FASEB J. 1992;6(2):745-8.
18. Guengerich FP. Influence of nutrients and other dietary materials on cytochrome P-450 enzymes. Am J Clin Nutr. 1995;61:651S-658S.
19. WebMD. http://www.webmd.com/allergies/guide/salicylate-allergy. Accessed 3/12/2012.
20. Crinnion WJ. The benefits of pre- and post-chal-lenge urine heavy metal testing: Part 1. Altern Med Rev. 2009;14:3-8.
21. Crinnion WJ. The benefit of pre- and post-chal-lenge urine heavy metal testing: part 2. Altern Med Rev. 2009;14(2):103-8.
22. Dr. Crinnion. http://www.crinnionmedical.com/. Accessed 3/11/2012.
23. IFM. functionalmedicine.org. Accessed 3/11/2012.
Functional Laboratory Assessment of Detoxification and Biotransformation
Laboratory Testing HandoutPart I: Tests Grouped by the Functional Medicine Matrix23
Inflammatory ProcessBlood Amino AcidsBlood Fatty AcidsBlood Nutrient/Toxic ElementsBlood Food Antibody Blood ADMABlood Vitamin DBlood Lymphocyte Growth AssaysBlood Lipid Blood Antioxidant CapacityBlood Oxidant Stress Markers (e.g., Glu-tathione)Blood Hs-CRP, Ferritin, and/or FibrinogenBlood SNP Genomic TestsUrinary Toxic Metals (provoked and unprovoked)Urinary Organic AcidsUrinary Oxidant Stress Markers Fecal LysozymeFecal LactoferrinFecal Calprotectin
Hormone and Neurotransmitter RegulationBlood Amino AcidsBlood Fatty AcidsBlood Food AntibodyBlood Estrogen, Progesterone, Testoster-one, DHEA, SHBGBlood Estrogen MetabolitesBlood Vitamin DBlood Lymphocyte Growth AssaysBlood Lipid Blood Thyroid Function (T3, T4, TSH, RT3, antibody)Blood Insulin/GlucoseBlood SNP Genomic Tests Urinary Organic AcidsUrinary Toxic Metals (provoked and unprovoked)Urinary Amino AcidsUrinary Estrogen MetabolitesUrinary IodideUrinary Neurotransmitter Metabolites
Salivary Estrogen, Progesterone, Testos-teroneSalivary Cortisol, DHEASalivary Melatonin
Digestion, Absorption and Barrier IntegrityBlood Fatty AcidsBlood Food AntibodyBlood H. PyloriBlood Candida Antibody/AntigenBlood Celiac ProfileBlood Lymphocyte Growth AssaysBlood Lipid Urinary Organic AcidsUrinary Lactulose/Mannitol Fecal LysozymeFecal LactoferrinFecal Ova & ParasitesFecal Bacteriology Culture Fecal Short-Chain Fatty AcidsFecal Digestive Elements
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Fecal Absorptive ElementsFecal Mycology Culture Fecal H. Pylori AntigenFecal Clostridium Difficile Toxins A & BFecal Enterohemorrhagic E. Coli Cyto-toxin Fecal Elastase-1Fecal CalprotectinBreath Lactose IntoleranceBreath Small Intestine Bacterial Over-growth
Detoxification and BiotransformationBlood Amino AcidsBlood Nutrient/Toxic Elements Blood Estrogen MetabolitesBlood Oxidant Stress Markers (e.g., Glu-tathione)Blood Lymphocyte Growth AssaysBlood Antioxidant CapacityBlood SNP Genomic TestsUrinary Organic Acids Urinary Amino AcidsUrinary Toxic Metals (provoked and unprovoked)Urinary Estrogen MetabolitesUrinary Challenge Detox ProfilesUrinary Mercapturic and D-Glucaric AcidsUrinary Oxidant Stress Markers Fecal Toxic Metals
Hair Toxic MetalsOxidative/Reductive HomeodynamicsBlood Amino Acids Blood Nutrient/Toxic ElementsBlood ADMABlood Estrogen MetabolitesBlood Vitamin DBlood Oxidant Stress Markers (Glutathi-one)Blood Antioxidant CapacityBlood Lymphocyte Growth Assays Blood SNP Genomic TestsUrinary Organic AcidsUrinary Oxidant Stress Markers Urinary Amino AcidsUrinary Toxic Metals (provoked and unprovoked)Urinary Estrogen MetabolitesUrinary Challenge Detox Profiles Immune SurveillanceBlood Amino Acids Blood Nutrient/Toxic ElementsBlood Food AntibodyBlood Vitamin DBlood Mold/Yeast AntibodyBlood Celiac ProfileBlood Lymphocyte Growth AssaysBlood Antioxidant CapacityBlood SNP Genomic Tests
Urinary Organic AcidsUrinary Amino AcidsUrinary Toxic Metals (provoked and unprovoked)Fecal Secretory IgA Psychological and Spiritual Equilib-riumBlood Amino Acids Blood Nutrient/Toxic ElementsBlood Lymphocyte Growth AssaysBlood Antioxidant CapacityBlood Fatty AcidsUrinary Organic AcidsUrinary Amino AcidsUrinary Toxic Metals (provoked and unprovoked)Hair Toxic Metals Structural IntegrityBlood Nutrient/Toxic ElementsBlood Vitamin DBlood Lymphocyte Growth AssaysBlood Antioxidant CapacityBlood Lipid Urinary Organic AcidsUrinary Toxic Metals (provoked and unprovoked)Urinary Bone ResorptionUrinary Amino Acids
Laboratory Testing HandoutPart I: Tests Grouped by the Functional Medicine Matrix
Blood ADMAPlasma asymmetric dimethylarginine (ADMA) is a primary endogenous inhibitor of nitric oxide synthase that inhibits nitric oxide production. Elevated levels are im-plicated in cardiovascular disease and are a cause of hypertension, hyperhomocyste-inemia, diabetes mellitus types 1 & 2, and pre-eclampsia. ADMA becomes elevated due to loss of activity for the ADMA-de-grading enzyme DDAH when antioxidant protection is lacking.
Blood Amino AcidsAmino acid analyses aid in the assessment of: dietary protein adequacy and balance, gastrointestinal dysfunctions, forms of
protein intolerance, nutritional deficien-cies (vitamins, minerals), renal and hepatic dysfunction, psychiatric abnormalities, susceptibility to inflammatory response and oxidative stress, reduced detoxifica-tion capacity, susceptibility to occlusive arterial disease, and many inherent disor-ders of amino acid metabolism. Many free amino acids such as histidine, lysine, threo-nine and serine in plasma provide toxic element ligands for transport and renal excretion. Amino acid hepatic flux stimu-lates carcinogenic toxicant conjugation reactions. Amino acid analysis also shows phase II biotransformation substrates (gly-cine and sulfur amino acids) and status of glutathione precursor amino acids me-
thionine and glycine. Fasting plasma and whole blood (bloodspot) levels provide a reliable assessment of dietary adequacy. Plasma hydroxylysine and hydroxyproline become elevated due to increased rates of bone resorption.
Blood Antioxidant CapacityT-lymphocytes are cultured under op-timal growth conditions and, following mitogenic stimulation, are exposed to in-creasing concentrations of free radicals to measure the cell’s ability to resist oxidative stress. Specific antioxidants (i.e., selenium, tocopherols, glutathione, Coq10, etc.) are available to identify specific intracellular functional deficiencies that may limit anti-
Part II: Brief Descriptions of Functional Laboratory Tests (Tests are organized alphabetically using the names shown in Part I above.)
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oxidant capacity within a highly interactive system of antioxidants.
Blood Candida Antibody/AntigenSerum IgM, IgG, IgA antibodies for Can-dida albicans are used to indirectly assess current, past, and mucosal exposure to this yeast, respectively. Serum Candida al-bicans (antigen) is measured to identify its presence in circulation. Candida is associat-ed with both acute and chronic conditions.
Blood Celiac ProfileTotal immunoglobulins A, tissue transglu-taminase IgA, and anti-gliadin IgA are mea-sured. An elevated tissue transglutamin-ase IgA is highly sensitive and specific for gastrointestinal villous atrophy associated with Celiac. An elevated anti-gliadin IgA in-dicates specific gluten-activated immune response.
Blood Estrogen MetabolitesBlood estrogen metabolites include 2-hydroxyestrone and 16-alpha-hy-droxyestrone, and reflect how estrogen is being processed in the body. Blood sampling provides a direct assessment of circulating estrogen metabolites that act directly on target tissues. Imbalances of these metabolites are associated with car-diovascular disease, depression, osteopo-rosis, lupus, and breast cancer.
Blood Estrogen, Progesterone, Testos-terone, DHEA, SHBGSerum assays provide an accurate and time-tested assessment of estrogen, pro-gesterone, testosterone, and DHEA at a point in time. Sex hormone binding globu-lin (SHBG) is also measured in serum to pro-vide an estimate of free testosterone and estradiol, which are primarily bound by this protein. These hormones are assessed to evaluate ovarian and adrenal dysfunc-tion, and to determine need and dose of related hormone replacement therapy.
Blood Fatty Acids (plasma, RBC, blood spot)Fatty acid (FA) profiles show quantitative results for individual fatty acids, including polyunsaturated omega-3 (including ALA, EPA, DHA), omega-6 (including GLA, DGLA, AA), omega-9 (including oleic, nervonic), saturates (including capric, palmitic, stea-
ric, hexacosanoic), and trans-fatty acids. Fatty acid ratios such as LA/DGLA and AA/EPA are calculated to help identify imbal-ances. Essential FA deficiencies and meta-bolic effects manifest as imbalances within and between families of fatty acids.
Blood Food AntibodySemi-quantitative levels of serum IgE or IgG subclass responses to 30-90 common foods are used to identify food allergy or sensitivity due to leaky gut and to custom-ize elimination/rotation diets.
Blood H. pyloriHelicobacter pylori is the bacterium that causes peptic ulcer disease and is associ-ated with increased risk of gastric cancer. Blood assays indirectly identify the pres-ence of H. pylori by measuring antibody levels in circulation.
Blood Hs-CRP, Ferritin, FibrinogenTesting for these acute phase protein markers in serum provides insight relevant to the inflammatory cascade, free iron modulation, and the clotting cascade, re-spectively.
Blood Insulin/GlucoseElevated fasting serum insulin indicates in-sulin insensitivity that produces increased serum triglycerides and LDL cholesterol. Euglycemia in this scenario is characteristic of the metabolic syndrome, which is asso-ciated with increased risk of cardiovascular disease and diabetes.
Blood Lipids Cardiovascular disease is a multifactorial process whose etiology encompasses both size and number of various lipoproteins. These include HDL and LDL subclasses, remnant lipoprotein, VLDL, and lipoprotein (a). Homocysteine, although not a lipopro-tein, is recognized as a contributing factor to hemostasis, neurological function, and cardiovascular disease, and is easily mea-sured in blood lipid studies.
Blood Lymphocyte Growth AssaysT-lymphocytes are grown in tissue culture by mitogenic stimulation of proliferation. By culturing the cells under a variety of conditions, functional deficiencies of vita-mins, minerals, amino acids, antioxidants
and other micronutrients can be assessed. The assays are a long-term indicator of nu-tritional status and are useful not only in the identification of functional deficiency states, but also in monitoring the effective-ness of repletion to achieve optimal intra-cellular function of the cofactors within cellular metabolism.
Blood Mold and Yeast Mold and yeast blood antibody testing is used to assess for the immunologic reac-tion to these potential toxins. Mold and yeast exposures are associated with vari-ous acute and chronic conditions.
Blood Nutrient and/or Toxic ElementsWhole blood element analysis is a diag-nostic method that assists in determining deficiencies, excesses, and imbalances of essential elements, as well as recent or on-going exposure to specific toxic elements. Whole blood analysis measures total ele-ment levels that circulate extracellularly (serum/plasma) as well as intracellularly (function within blood cells). RBC element levels are very useful for assessing: cardio-tonic influences (magnesium, potassium); anti-inflammatory processes (selenium, copper, zinc); anemia (copper, iron); immu-nological function (zinc, copper, magne-sium); and glucose tolerance (chromium, manganese, and possibly vanadium). Ac-curate assessment of essential element status aids in determination of appropriate supplementation.
Blood Oxidant Stress MarkersPlasma amino acid testing reveals ability to maintain fasting blood levels of glutathi-one precursors methionine, homocysteine and glycine (taurine adds a further assess-ment of sulfur metabolism). Total body oxidant stress is evaluated with serum lipid peroxides. Erythrocyte elemental analysis is used to assess essential elemental cofac-tors, selenium, zinc, copper and manga-nese for redox-balancing enzymes like su-peroxide dismutase, and elevation of toxic elements that contribute to oxidant stress.
Blood SNP Genomic TestsGenomic testing identifies specific varia-tions in nucleic acid sequencing called single nucleotide polymorphisms (SNPs).
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SNPs can influence many different func-tions:
Detoxification: SNPs can alter the ki-netics of enzyme activity, affecting phase I and phase II detoxification and folic acid activation. Identification of these SNPs may indicate the need for lifestyle adjustments and nutritional supplementation that sup-port normal enzyme activity, and highlight environmental exposures that possess in-creased toxicity.
Hormone and neurotransmitters:SNPs that affect induction and activity of enzymes that metabolize hormones and neurotransmitters may increase risk for re-lated cancers and mood disorders. Identifi-cation of these SNPs may indicate the need for lifestyle adjustments and nutritional supplementation that support normal en-zyme activity.
Immune: SNPs that affect the levels and activity of cytokines can modulate immune and inflammatory activity. These variations can affect balance between cell (Th-1) and humoral (Th-2) immunity and reveal potential defects in immune system defense.
Inflammatory: SNPs that affect the lev-els and activity of cytokines can modulate immune and inflammatory activity. These variations can affect balance between cell (Th-1) and humoral (Th-2) immunity, re-veal potential defects in immune system defense, and stimulate mechanisms lead-ing to chronic, overactive inflammatory re-sponses. Identification of these SNPs may indicate the need for lifestyle adjustments and nutritional supplementation that sup-port normal cytokine activity.
Oxidative stress: SNPs that affect the production or management of oxidative stress are associated with chronic illness. SNPs can alter protein induction and activi-ties that elevate oxidative stress, including phase I and II detoxification enzymes, su-peroxide dismutase, and cytokines.
Blood Thyroid function (T3, T4, TSH, RT3, and antibody)A comprehensive thyroid function analysis includes free T3, free T4, TSH, reverse T3, as well as thyroid peroxidase and thyro-
globulin antibodies. These tests are used to diagnose thyroid disease, and to deter-mine need for thyroid support, including need and dose of related thyroid hormone therapy.
Blood Vitamin DSerum 25-hydroxyvitamin D is the major circulating precursor to active 1, 25-dihy-droxy vitamin D. Low values show vitamin D deficiency and repeat testing allows monitoring of repletion in patients with osteoporosis or chronic inflammatory dis-orders.
Blood Vitamin ProfileMeasurement of serum concentrations of fat-soluble vitamins including A, E, CoQ10, beta-carotene, and lycopene allow direct assessment of dietary sufficiency for these key antioxidants, essential or conditionally essential nutrients.
Breath Lactose IntoleranceThis breath test identifies bacterial fermen-tation of lactose in the GI and indicates presence and severity of lactose intoler-ance.
Breath Small Intestine Bacterial Over-growthThis breath test identifies overgrowth of bacteria in the small intestine.
Fecal Absorptive ElementsLong-chain fatty acids, phospholipids, cho-lesterol, triglycerides, and total fecal fat are measured in the stool to assess malabsorp-tion. When poorly absorbed, these fecal fats will be elevated in the stool.
Fecal Bacteriology Culture Bacteria are cultured from stool samples to identify the presence and relative abun-dance of specific bacteria, both beneficial and dysbiotic. When dysbiotic bacteria are present, further testing is performed to de-termine which natural and pharmaceutical agents might eradicate these specific bac-teria.
Fecal CalprotectinCalprotectin is a neutrophil-derived pro-tein that is released in the GI tract in the presence of infectious, inflammatory, or malignant disease. This quantitative assay can identify mild, moderate and severe lev-
els of inflammation, and is FDA approved to differentiate irritable bowel syndrome (IBS) from inflammatory bowel disease (IBD). It can also be used to assess the ef-fectiveness of treatment and to predict re-lapse in IBD cases.
Fecal Clostridium Difficile Toxins A & BThe C. difficile toxin enzyme immunoas-say test is the standard diagnostic tool for identification of overgrowth of C. difficile bacteria in the gastrointestinal tract.
Fecal Digestive ElementsPancreatic elastase 1, chymotrypsin, short-chain fatty acids, meat fibers, and vegeta-ble fibers are used as an indirect evalua-tion of digestive function. These markers provide insight into inadequate digestive enzyme production and maldigestion.
Fecal ElastaseElastase, produced in the pancreas, is a pro-teolytic enzyme that breaks down dietary protein to absorbable amino acids and peptides. Fecal elastase levels are utilized to diagnose poor digestive capacity due to pancreatic exocrine function that may be associated with chronic pancreatitis, cystic fibrosis, carcinoma of the pancreas, type 1 diabetes mellitus, and other etiologies of pancreatic enzyme insufficiency.
Fecal Enterohemorrhagic E. coli Cyto-toxinMeasurement of these specific E. coli cyto-toxins in the feces is a reliable tool for the diagnosis of EHEC infections.
Fecal H. pylori AntigenThe fecal HpSA enzyme immunoassay (EIA) is a qualitative procedure for the de-tection of H. pylori antigens in stool. This noninvasive test’s specificity and sensitiv-ity for diagnosis of H. pylori infection are comparable to blood and tissue biopsy methods. The fecal H. pylori antigen is also excellent for assessing eradication treat-ment efficacy.
Fecal LactoferrinA highly sensitive and specific immunoas-say has recently been developed to mea-sure the fecal concentration of the inflam-matory protein lactoferrin. Lactoferrin is elevated in IBD, but not in IBS or dysbiosis,
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and serves as an important diagnostic tool for chronic GI symptoms. Fecal lactoferrin assessment is a noninvasive screening for IBD (Crohn’s disease and ulcerative colitis).
Fecal LysozymeLysozyme is secreted at sites of inflam-mation in the colonic mucosa. Lysozyme is a general marker for inflammation that is commonly elevated in the presence of dysbiosis. High fecal lysozyme levels may also accompany elevated fecal lactoferrin in IBD.
Fecal Mycology CultureIdentification of abnormal levels of specific yeast species in the stool is an important diagnostic step in therapeutic planning for the patient with chronic gastrointesti-nal and extra-gastrointestinal symptoms. Yeast sensitivities to a variety of prescrip-tive and natural agents are provided when yeast is cultured at any level. This provides the clinician with useful clinical informa-tion to help plan an appropriate treatment protocol.
Fecal Ova & ParasitesChronic gastrointestinal complaints are among the most common reasons that patients seek medical care. Fecal ova and parasite identification can identify a com-mon underlying cause of chronic or acute GI symptoms.
Fecal Secretory IgAThe humoral immune status of the GI tract can be assessed by determining the fecal concentration of sIgA. The sIgA secreted by mucosal-associated lymphoid tissue (MALT) represents a pivotal and specific line of defense in the GI mucosa. As the principal immunoglobulin isotype present in mucosal secretions, sIgA plays an impor-tant role in controlling the intestinal milieu.
Fecal Short-Chain Fatty Acids (SCFAs)SCFAs are the end product of the bacterial fermentation process of dietary soluble fi-ber by beneficial bacteria in the GI. SCFAs decrease inflammation, stimulate healing, and contribute to normal cell metabolism and differentiation.
Fecal Toxic MetalsFecal toxic metal analysis provides impor-
tant information about the potential for toxic metal burden. For many toxic met-als, fecal (biliary) excretion is the primary natural route of elimination from the body. Fecal elemental analysis also provides a direct indication of dietary/oral exposure to toxic metals, and can be used to gauge mercury exposure from dental amalgams.
Hair Toxic MetalsToxic metals may be 200-300 times more highly concentrated in hair than in blood or urine. Hair is the tissue of choice for de-tection of recent or ongoing exposure to elements such as arsenic, aluminum, cad-mium, lead, antimony, and mercury.
Salivary Cortisol, DHEAWhen cortisol is measured in four se-rial specimens (spanning from morning to bedtime on a day of typical stressor expo-sure), abnormalities of cortisol circadian re-lease in response to pituitary ACTH may be assessed. The average of the two mid-day salivary dehydroepiandrosterone (DHEA) levels allows inspection for depressed for-mation from cholesterol in protracted ad-renal dysfunction. Measurement of total sIgA allows detection of suppressed levels due to chronic elevated cortisol impact on the gut-associated immune tissue. Further evaluation of this impact is provided by in-spection for elevated anti-gliadin IgA.
Salivary Estrogen, Progesterone, Tes-tosteroneSalivary estrogen, progesterone, and tes-tosterone are convenient, noninvasive assays, measuring the free, bio-available form of these hormones. Salivary samples are collected at home, providing the op-portunity to evaluate ovarian and adre-nal function throughout their respective cycles, or to help account for mild fluctua-tions that occur in early menopause.
Salivary MelatoninSalivary melatonin is a convenient, nonin-vasive assay that is commonly used to as-sess the circadian secretion patterns over a complete light-dark cycle. This testing can reveal abnormal levels of melatonin that relate to various physical and psychologi-cal symptoms as well as premature accel-eration of the body’s aging process.
Urinary Lactulose/Mannitol Oral challenge with a lactulose/mannitol sugar solution and measurement of uri-nary excretion identifies increased intesti-nal permeability and malabsorption.
Urinary Amino AcidsAmino acid analyses aid in the diagnosis of: dietary protein adequacy and balance, gastrointestinal dysfunctions, forms of protein intolerance, nutritional deficien-cies (vitamins, minerals), renal and hepatic dysfunction, psychiatric abnormalities, susceptibility to inflammatory response and oxidative stress, reduced detoxifica-tion capacity, susceptibility to occlusive ar-terial disease, and many inherent disorders of amino acid metabolism. Amino acid he-patic flux stimulates carcinogenic toxicant conjugation reactions. Amino acid analy-sis also shows phase II biotransformation substrates (glycine and sulfur amino acids) and status of glutathione precursor amino acids methionine and glycine. Neurotrans-mitter and neurotransmitter precursor assessment is provided by measurement of phenylalanine, tyrosine, tryptophan, glycine, taurine and aspartic and glutamic acids. Urinary hydroxylysine and hydroxy-proline become elevated due to increased rates of bone resorption. Both specimens also show 3-methylhistadine rise in states of muscle catabolism.
Urinary Bone ResorptionUrinary deoxypyridinoline (uDPD) assess-ment shows excretion of type I collagen peptide that is elevated when bone re-sorption increases to supply ionic calcium for critical cardiac and brain functions. Treatment efficacy can be monitored by repeat testing.
Urinary Challenge Detox ProfilesChallenge with caffeine, acetaminophen, and salicylic acid, with timed collection of urine and saliva, allows assessment of capacities for hepatic biotransformation phase I and II pathways, including CYP450 1A2, sulfation, glucuronidation, and glyci-nation to meet toxin load demands. Mea-sured compounds show the rate of Phase I caffeine clearance and percentage conver-sion of challenge compounds to oxidized,
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sulfated, glucuronidated, and glycinated products.
Urinary Estrogen MetabolitesUrinary 2-hydroxyestrone, 2-hydroxyestra-diol and 16-hydroxyestrone and the calcu-lated 2/16 ratio are measured to assess the function of the primary (hepatic CYP1A1) and secondary CYP1B1 estrogen clearance pathways. A 2/16 ratio less than 2 is associ-ated with increased risk of developing es-trogen sensitive cancers. Extensively stud-ied diet and food supplement regimens can be used to increase CYP1A1 activity to raise the ratio.
Urinary IodideIodine/Iodide is an essential element that is pivotal to normal function of the thy-roid gland and the health and integrity of breast tissue. Iodine/Iodide intake has de-creased significantly over the past thirty years and clinical symptoms have become more apparent. Iodine/Iodide sufficiency can be assessed by analysis of urinary io-dide excretion with or without a loading protocol.
Urinary Mercapturic and D-glucaric Ac-idsUrinary D-glucaric acid, a byproduct of phase I detoxification, is a valuable indi-cator of chemical exposure or liver dam-age. Urinary mercapturic acids are direct
end-product metabolites of conjugated xenobiotics. Combined assessment of the urinary levels of the two analytes provides valuable information about exposure to xenobiotics and liver disease, and the ca-pability of the liver to eliminate toxins.
Urinary Neurotransmitter MetabolitesUrinary organic acid profiles show low or high levels of principal catabolites of nor-epinephrine and epinephrine (homovani-late) and dopamine (vanilmandelate). These catecholamine metabolites reveal total body turnover that is depressed when the precursor amino acids phenylalanine and tyrosine are insufficient. Elevated lev-els found in patients with chronic stress response are a sign of accelerated utiliza-tion of the precursors that is antecedent to development of insufficiency. Similarly, the serotonin catabolite 5-hydroxyindol-acetic acid reveals serotonin turnover and risk of tryptophan depletion. Simultaneous reporting of quinolinic acid and kynurenic acids allows inspection for inflammatory cytokine stimulation of glutamatergic neu-ronal activity.
Urinary Organic AcidsThe full profile of organic acids in urine provides information on functional nutri-ent deficiencies, mitochondrial efficiency, methylation pathway cofactor sufficien-
cies, neurotransmitter metabolites, oxi-dant stress, detoxification and dysbiosis markers. A primary biochemical commu-nication from the immune system to the CNS is assessed by measuring urinary interferon gamma-stimulated quinolinic acid (NMDA agonist) and kynurenic acid (NMDA antagonist).
Urinary Oxidant Stress MarkersUrinary 8-hydroxy-2’-deoxyguanosine re-veals oxidative damage to DNA. Urinary organic acid profiles include p-hydroxy-phenyllactate (elevated in conditions of increased cell proliferation such as cancer or chronic organ stress); alpha-hydroxybu-tyrate (elevation shows increased glutathi-one demand); pyroglutamate (elevation reveals glutathione wasting); and sulfate (low levels indicate total body glutathione depletion).
Urinary Toxic Metals (provoked and un-provoked)Urinary metal analysis is an invaluable tool for the diagnosis or confirmation of toxic element burden and monitoring of detoxi-fication therapy. A challenge consisting of pre and post provocation testing is recom-mended for diagnosing the presence of toxic element burdens.
Part II: Brief Descriptions of Functional Laboratory Tests
30. Minich DM, Bland JS, Katke J, et al. Clinical safety and efficacy of NG440: a novel combination of rho iso-alpha acids from hops, rosemary, and oleanolic acid for inflammatory conditions. Can J Physiol Pharmacol. 2007;85:8728-8783.
31. Minich DM, Bland JS. Dietary management of the metabolic syndrome beyond macronutrients. Nutr Rev. 2008;66:429-444.
32. Ray SD, Patel N, Shah N, et al. Pre-exposure to a novel nutritional mixture containing a series of phytochemicals prevents acetaminophen-induced programmed and unprogrammed cell deaths by enhancing BCL-XL expression and minimizing oxidative stress in the liver. Mol Cell Biochem. 2006;293:119-136.
33. Davis DL, Telang NT, Osborne MP, Bradlow HL. Bi-functional genetic-hormonal pathways to breast cancer. Environ Health Perspect. 1997;105:571-576.
34. T Rogan EG. The natural chemopreventive com-pound indole-3-carbinol: state of the science. In
Vivo. 2006;20:221-228.
35. Minich DM, Bland JS. A review of the clinical ef-ficacy and safety of cruciferous vegetable phyto-chemicals. Nutr Rev. 2007;65:259-267.
36. Lamb JJ, Konda VR, Quig DW, et al. A program consisting of a phytonutrient-rich medical food and an elimination diet ameliorated fibromyal-gia symptoms and promoted toxic-element de-toxification in a pilot trial. Altern Ther Health Med. 2011;17:36-44.
37. Lerman RH, Minich DM, Darland G, et al. Subjects with elevated LDL cholesterol and metabolic syndrome benefit from supplementation with soy protein, phytosterols, hops rho iso-alpha ac-ids, and Acacia nilotica proanthocyanidins. J Clin Lipidol. 2010;4:59-68.
38. Lerman RH, Minich DM, Darland G, et al. En-hancement of a modified Mediterranean-style, low glycemic load diet with specific phyto-chemicals improves cardiometabolic risk fac-tors in subjects with metabolic syndrome and
hypercholesterolemia in a randomized trial. Nutr Metab. 2008;5:29.
39. Jones JL, Park Y, Lee J, Lerman RH, Fernandez ML. A Mediterranean-style, low-glycemic-load diet reduces the expression of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase in mononuclear cells and plasma insulin in women with metabol-ic syndrome. Nutr Res. 2011;31:659-664.
40. Jones JL, Fernandez ML, McIntosh MS, et al. A Mediterranean-style low-glycemic-load diet improves variables of metabolic syndrome in women, and addition of a phytochemical-rich medical food enhances benefits on lipoprotein metabolism. J Clin Lipidol. 2011;5:188-196.
41. Schiltz B, Minich DM, Lerman RH, et al. A science-based, clinically tested dietary approach for the metabolic syndrome. Metab Syndr Relat Disord. 2009;7:187-192.
42. Minich DM, Bland JS. Dietary management of the metabolic syndrome beyond macronutrients. Nutr Rev. 2008;66:429-444.
What is a “Detoxification Diet?” from page 71
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ADULT TOXIN EXPOSURE QUESTIONNAIRE
If you have been exposed to any of these in the LAST 12 MONTHS please check: • (Y) Yes • (N) No • (?) Unknown • (P) for exposure more than 12 months ago
Community
Home and/or Work Environment
Do you have regular exposure to: Y N ? P Notes
Automobile exhaust Farm/Industrial/Power plant or lines Radio tower Landfill/Dump Hydro tower
Do you live in a: (Circle one) House Apartment Building Mobile Home Do you work in a: (Circle one) House Office Building Factory Bathing/Showering water source: (Circle one) Well Public Works Bottled
Do you have regular exposure at home or work to: Y N ? P Notes
Forced air heat Renovations (new carpets; add ons; etc…) Basement cracks or dirt floor Damp basement or crawl space Wet windows or outside closet walls Water leaks (ceilings, walls, floors) Visible mold Old or cracking ceiling tiles Old or cracking vinyl linoleum flooring Crumbling pipe insulation Crumbling wall or ceiling insulation Old or cracking paint Carpets or rugs Stagnant or stuffy air Gas or propane stove Coal or wood stove Other gas appliance (water heater, furnace) Regular contact with smokers
Adult Toxin Exposure Questionnaire23
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Adult Toxin Exposure QuestionnaireHobby and Work Activities
Personal - Diet
Do you have regular exposure to: Y N ? P Notes
Pesticides or herbicides Harsh chemicals (varnish, glue, gas, acid…) Welding or soldering Metals (Lead, Mercury, etc) Paints Photo developing / Dark room Airplane travel Cleaning chemicals
Drinking/Cooking water source: Well Public Works Bottled Filtered Caffeine? What kind: How Much: Do you regularly eat: Y N ? P Notes Fish (fresh, frozen, canned, etc.) Artificial sweeteners (Circle one): NutraSweet, Equal, Aspartame, Splenda Alcohol Animal products
• How often? • What percentage of your animal product is organic?
Do you wash your produce • What percentage of your produce is organic?
Deep fat fried foods Sodas, juices, drinks containing High Fructose Corn Syrup – how many per day?
Do you have: Y N ? P
Allergies Sensitivity to smells (gas, perfume, paint, etc…) Artificial materials in the body (implants, pins, joints, etc…) Immunizations
Have you ever: Y N ?
Used tobacco Experimented with recreational drugs Led a high stress lifestyle Experienced a stressful or traumatic event Been under anesthesia
Had an illness during foreign travel Had an illness while camping or hiking Had food poisoning
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Dental
Please list all PRESCRIPTION or OVER THE COUNTER medications you currently take on a regular basis, including birth control pills and allergy injections:
Name of medication Dose (mg, ML, IU) How often do you take it?
How long have you taken it?
If you have side effects, please specify
Please list all VITAMINS/MINERALS, HERBS, or OTHER SUPPLEMENTS you currently take on a regular basis:
Name of supplement Dose (mg, ML, IU) How often do you take it?
How long have you taken it?
If you have side effects, please specify
Drug Adverse Reactions: Please list ANY medication / anesthetics / immunizations you have had to stop taking because of side effects or allergic reactions:
Name of medication/ immunization
Type of side effects or allergic reaction that caused you to stop it Age Year
Y N ? Notes Do you currently have amalgam fillings or caps?
• How many amalgam fillings do you have now? Have you removed or lost dental fillings or caps? Did you have fillings as a child?
• How many fillings did you have? Did you have your Wisdom teeth removed?
• At what age? • Any complications such as dry socket or abscesses?
Do you have any root canal treated teeth? • How many and when were they placed?
Did your mother have dental fillings prior to giving birth to you?• During her pregnancy with you?
Other:
Adult Toxin Exposure Questionnaire
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Resource Review
Therapeutic Fasting: The Buchinger Amplius MethodFrancoise Wilhelmi de Toledo, MD, and Robert HohlerThieme (New York) 2012: 156 ppSoftcover, $34.99ISBN 978-3-13-160361-6
For professionals wanting to educate themselves on detoxifica-tion diets, it is refreshing to find a comprehensive book written by an experienced medical expert. In Therapeutic Fasting: The Buchinger Amplius Method, Francoise Wilhelmi de Toledo, MD, writes with passion and conviction about her life’s work. The book is translated from the original German.
Wilhelmi de Toledo has published numerous scientific papers on therapeutic fasting and is the medical director of the Buch-inger Fasting clinics. The Buchinger Amplius Fasting Method was originally developed by the author’s father-in-law, German Physician Otto Buchinger (1878-1966). The Maria Buchinger foundation website is a great source of scientific informa-tion on therapeutic fasting and can be found at: http://maria-buchinger-foundation.com/en/fasten/scientific-publications.
The book opens with an intriguing explana-tion of fasting as an “evolutionary adapta-tion to the climatic conditions on our planet,” when the availability of food changed with the seasons and before the conveniences of modern agriculture and food preservation. According to the fasting principles, when you “temporarily and voluntarily abstain from eating,” your metabolism switches automatically from “external nutrition to nutrition taken from fat reserves.” After the first three days of a therapeutic fast, fat metabolism increases (as ketones are formed) and amino acid transformation to glucose (gluco-neogenesis) is minimized. The therapeutic explanation of the benefits of protein breakdown were a little surprising and quite interesting. On page 33, the author writes “from a naturopathic point of view, fasting offers the opportunity to metabolize old,
pathological, and dispensable protein structures or molecules,” such as “proteins damaged by free-radicals, antigen-antibody immune complexes, and AGEs (advanced glycation end prod-ucts); for example, carcinogen acrylamides contained in potato chips and French fries.”
The Buchinger Amplius Method is a modified fast that includes fresh vegetable broth, fruit and vegetable juices, water and herbal teas (for a total of about 250 calories per day). The fast-ing method is presented in great detail and intended to be carried out under medical supervision by a physician and/or a well-trained fasting counselor. A table on page 35 lists abso-lute contraindications to fasting, including cachexia, and rela-tive contraindications such as cancer, that require experienced medical care. The approach is holistic and includes spiritual-re-ligious, socio-humane, and medical-physical dimensions. Tech-
niques and detailed instructions provided for enhancing the fast include breathing, yoga, massage, hot liver packs, and daily colonic ir-rigation, to name a few. Although the thera-peutic fast is a 10 day fast that includes 5 tran-sitional days and 5 days of fasting, the case is made for occasional transitional “detox” days for the anti-aging and rejuvenating effects of temporary calorie restriction.
The book concludes with low calorie whole food recipes and menus to be used during and after the fast. Some of the recipes are quite interesting, such as the nutrient dense Budwig cream, but knowledge of European
ingredients would be helpful and be sure to have your metric conversions handy. Other practical information includes an in-teresting discussion with Chef Hubert Hohler from the Buch-inger Fasting Clinics about cooking with cold pressed oils and whole grains.
Barbara Goldman MS, RD, CDE, Associate Professor of Nutrition, Palm Beach State College Contact Barbara at: [email protected].
Resource Review
The Happiness Diet: A Nutritional Prescription for a Sharp Brain, Balanced Mood, and Lean, Energized BodyTyler Graham and Drew Ramsey, MDwww.thehappinessdietbook.com2011:288 pages, hardcover, $25.99ISBN 978-60529-327-1
The Happiness Diet is a why-to and how-to guide for anyone interested in exploring how diet impacts overall health, par-ticularly mood, mental health and brain function, and taking a “foods first” approach to healing. The overall sensible advice offered in the book takes a specific stance when it comes to di-
etary fats, defending dietary cholesterol and wholefood sources of organic, pasture-raised animal fats and criticizing highly pro-cessed vegetable fats, like trans fats.
The book is organized into two major parts: part one focuses on the effects of foods on the brain, providing a brief history of the Modern American Diet (MAD), describing “Bad Mood” foods and “Good Mood” foods. The book describes and implicates MAD as a major contributor of obesity and diabetes, as well as all too common mental diseases, ranging from depression and anxiety to Parkinson’s and Alzheimer’s Diseases. MAD is notably high in sugar and overly processed vegetable fats, both relatively new to the human diet, and the authors detail the historical timeline
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Resource ReviewCommentary
ALOX5 Gene Variants Affect Eicosanoid Production and Response to Fish Oil Supplementation Stephensen CB, Armstrong P, Newman JW, et al. J Lipid Res. 2011, 52(5):991-1003. Epub 2011 Feb 4.
Abstract
The objective of this study was to determine whether 5-lipoxy-genase (ALOX5) gene variants associated with cardiovascular disease affect eicosanoid production by monocytes. The study was a randomized, double-masked, parallel intervention trial with fish oil (5.0 g of fish oil daily, containing 2.0 g of eicosap-entaenoic acid [EPA] and 1.0 g of docosahexaenoic acid [DHA]) or placebo oil (5.0 g of corn/soy mixture). A total of 116 subjects (68% female, 20-59 years old) of African American ancestry en-rolled, and 98 subjects completed the study. Neither ALOX5 pro-
tein nor arachidonic acid-derived LTB4, LTD4, and LTE4 varied by genotype, but 5-hydroxyeicosatetraenoate (5-HETE), 6-trans-LTB4, 5-oxo-ETE, 15-HETE, and 5,15-diHETE levels were higher in subjects homozygous for the ALOX5 promoter allele containing five Sp1 element tandem repeats (“55” genotype) than in sub-jects with one deletion (d) (three or four repeats) and one com-mon (“d5” genotype) allele or with two deletion (“dd”) alleles. The EPA-derived metabolites 5-HEPE and 15-HEPE and the DHA-derived metabolite 17-HDoHE had similar associations with genotype and increased with supplementation; 5-HEPE and 15-HEPE increased, and 5-oxo-ETE decreased to a greater degree in the 55 than in the other genotypes. This differential eicosanoid response is consistent with the previously observed interaction of these variants with dietary intake of omega-3 fatty acids in predicting cardiovascular disease risk.1
The following is a commentary on the above abstracted article
that has led to these components’ prominence in the modern world. Also discussed were the studies that demonized dietary fats and cholesterol, as well as the inherent weaknesses and flaws in those studies. Bad Mood foods include sugar and refined carbohydrates, industrially manufactured vegetable fats, conventionally raised animal foods and vegetables imported from far-flung places, bred for transport and storage rather than flavor. Good Mood foods are minimally refined or processed foods that provide 12 key nutrients referred to as the “Essential Elements of Happiness,” like vitamin B12, iodine, magnesium and others, which are described by their ac-tions in the body and what happens when the body is depleted of those nu-trients. Best food sources are provided for each nutrient.
Part two delves into which foods to eat, divided into foods for focus, energy and mood. Free range eggs, grass-fed beef and milk are praised for their brain sup-porting fats, and a strong case is made for diets high in phyto-chemical-rich fruits and vegetables, nutrient-dense nuts, low contaminant fish, leafy greens, legumes, and even coffee and cocoa. The stance on produce is resoundingly pro-organic and local, and the authors include information on the effects of pes-ticides on the body as well as in the environment, which may ap-peal to many readers. This section also offers tips on food shop-ping, storage and preparation, as well as recipes and meal plans.
Sprinkled throughout the book are “Top 100 Reasons to Avoid Processed Foods” factoids, which address a wide variety of rea-
sons to shun processed foods, from potential cancer-causing ef-fects of blue dye No. 2 (used in textiles and found in blue M&Ms) to the specific effects of various preservatives, pesticides and
other additives found in highly processed foods. Also included are gross-out details of common junk foods, like rot allowanc-es in potato chips and allowable maggot content of maraschino cherries.
The authors boldly name names, as they discuss the origins of Crisco by then-soap makers Procter & Gamble and Coca Cola, point out the ill effects of Pringles’ Oles-tra, and the chemicals created by Mon-santo that are found in Old El Paso Taco Dinners. Also mentioned by name are Mountain Dew, Fruit Roll Ups, Dannon, McDonalds and Wonder Bread. Perhaps reading the specific criticisms of such recognizable brands may strengthen the message among consumers.
Overall, this book would be a good read for patients and clients interested in im-
proving their eating habits, but who may need a little convinc-ing as to why they should they should stop fearing minimally processed fats from a variety of minimally processed foods, cut industrially manufactured foods and move to a more locally grown, whole foods diet. It would also be helpful for the many people who struggle with mild mood disorders, like depression, who would like to use a foods-first approach to improve mood and overall health.
Robin Foroutan, MS, RD, HHC is an Integrative Nutritionist in private practice and the DIFM Communications Chair for 2012-2013. Con-tact Robin at [email protected].
Resource Review: The Happiness Diet
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posted to the ISSN website by Raffaele De Caterina, MD, PhD. “G. D’Annunzio” University – Chieti – Italy. For inquiries regarding the commentary, please contact Dr. DeCaterina at [email protected].
Eicosanoids are lipid mediators of inflammation, and include a variety of compounds (prostaglandins, thromboxanes, leukotri-enes (LT), hydroxy- and epoxy-fatty acids, lipoxins and isopros-tanes) derived from the ubiquitous 20 (in Greek: eicosa)-carbon atom arachidonate and a few similar polyunsaturated fatty ac-ids. Esterified in phospholipids of biological membranes, these fatty acids are released upon a variety of stimuli, becoming sub-strates for metabolizing enzymes. More than 20 years ago, Sam-uelsson and coworkers identified LT as a class of eicosanoids de-rived through the action of 5-lipoxygenase (5-LO). This enzyme, selectively expressed in bone marrow-derived cells such as neutrophils, monocytes, macrophages, dendritic cells and mast cells, catalyzes the transformation of arachidonic acid (AA) into LTA4. In turn, LTA4 is either converted by enzymatic hydrolysis into LTB4, or is conjugated with glutathione to form LTC4. LTC4 and its metabolites LTD4 and LTE4 are together referred to as “cysteinyl”(cys)-LT. LTB4 is a potent chemoattractant for neutro-phils, macrophages and other inflammatory cells, and induces the chemokinesis and adhesion of these cells to the vascular en-dothelium. On the other hand, cys-LT increase vascular perme-ability and contract smooth muscle cells, causing broncho- and vasoconstriction. LT have been identified as mediators of a vari-ety of inflammatory and allergic conditions including rheuma-toid arthritis, inflammatory bowel disease, psoriasis and allergic rhinitis, but their most relevant pathophysiological implication has so far been bronchial asthma. Blockers of the cys-LT1 recep-tor or of 5-LO have been marketed worldwide as effective anti-asthmatic medications.
The transcription rate of the 5-LO gene (located in humans on chromosome 10, and conventionally termed ALOX5) is con-trolled by its promoter, and particularly by a region, termed core promoter, containing a sequence of GC-rich tandem repeats, which are binding sites for two transcription factors, Sp-1 and Egr-1. Genetic variants in the core promoter region may change the binding of these transcription factors and the rate of 5-LO transcriptional activation under inflammatory conditions. In-deed, a family of mutations in the GC-rich region, consisting of the deletion of one, deletion of two, or addition of one such binding sites, was associated with altered (reduced) transcrip-tion of the 5-LO gene compared to the common allele. It was then found that carriers of these genetic variants had dimin-ished clinical responses to treatment with anti-LT drugs, indi-cating a pharmacogenetic effect of the promoter sequences on treatment responses.
Originally confined to the area of asthma, these findings more recently expanded their implications to atherosclerosis.
In search for candidate genes contributing to atherosclerosis susceptibility in two widely used mouse models of atheroscle-rosis, the apo-E -/- mice, and the LDL-receptor -/- mice, a locus on mouse chromosome 6 was found to confer almost total re-sistance to atherogenesis. The ALOX5 gene, located in this locus in the mouse, turned out to totally account for this effect, since LDL receptor -/- mice missing even only one of the two allelic copies of the 5-LO gene had a dramatic decrease (about 26-fold) in lesion development. Also, when bone marrow (supplying cir-culating blood cells) from 5-LO -/- mice was transplanted into LDLR -/- there was a significant protection from atherosclerosis, suggesting that 5-LO from white blood cells (likely monocyte-macrophages) was necessary for atherogenesis.
The important contribution of 5-LO to atherosclerosis may oc-cur because the products of 5-LO, LT, mostly produced by mono-cyte-macrophages or dendritic cells in the arterial intima, would foster the chemoattraction of monocytes, T-cells or other circu-lating cell types within the vessel wall and/or increase vascular permeability. This creates a vicious cycle in which inflammatory cells, by producing these lipid mediators, beget local vascular in-flammation perpetuating the recruitment of inflammatory cells and the further production of mediators. 5-LO might also con-tribute by oxidizing LDL or producing natural ligands for nuclear receptors, such as peroxisome proliferator-activated receptor a (PPARa).
Genetic variants of the 5-LO promoter, previously described as associated with variable sensitivity to anti-asthmatic medica-tions, also influence atherosclerosis. A few years ago, Dwyer and coworkers reported that this is apparently the case. ALOX5 gene variants were found in 6% of a cohort of 470 healthy middle aged women and men. Frequent variations occur especially in the promoter region of the ALOX5 gene, which has from 3 to 8 tandem repeats of a consensus binding site for the transcrip-tion factors Sp1 and Egr1. The most frequent allele has 5 such repeats. Variant alleles with 3 or 4 sites (or, rarely, >5 sites) are associated with greater intima-media thickness of the carotid artery in healthy adults from Los Angeles and with occurrence of a first myocardial infarction (MI) in a case-control study in Cos-ta-Ricans. In both studies, the observed diet-gene interactions were more pronounced in subjects with high dietary AA intake and carrying the deletion variants (i.e., “3” or “4” repeats, referred to jointly as “deletion” (“d”) alleles) relative to subjects with two common alleles (i.e., the “55” genotype). Conversely, in the Los Angeles study, this atherogenic effect was reversed in the sub-jects with the “d” alleles having high eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake. Since EPA and DHA may decrease the formation of LT by competing with arachido-nate as substrates for 5-LO and also generate the weaker LT of the 5-series, those findings suggested that the antiatherogenic
Resource Review: ALOX5 Gene Variants Affect Eicosanoid Production and Response to Fish Oil Supplementation
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effects of fish-derived EPA and DHA might be more prominent in (or perhaps limited to) genotype variants favoring increased 5-LO activity.
The direction of the change in IMT in the “d” variant group was however contrary to what one would have expected on the ba-sis of previous findings in vitro, and rather consistent with in-creased, rather than decreased, 5-LO promoter activity associ-ated with the mutant alleles. This issue clearly deserved further investigation through measurements of 5-LO expression and of LT and other eicosanoids in these genetic variants, and evalua-tion of the interaction with recently identified mutations in oth-er genes related to LT production, such as that of 5-lipoxygenase activating protein (FLAP).
In this latest report by Stephensen et al., from the same group initially reporting the nutrigenetic effects of fish oil across ALOX5 variants, the authors now aimed at determining if ALOX5 vari-ants associated with cardiovascular disease affect eicosanoid production by monocytes. The study was a randomized, double-masked, parallel intervention trial with fish oil (5.0 g fish oil daily containing 2.0 g eicosapentaenoic acid [EPA] and 1.0 g docosa-hexaenoic acid [DHA]) or placebo oil (5.0 g of a corn/soy mix). 116 subjects (68% female, 20 - 59 yr) of African American ances-try enrolled and 98 completed the study. Contrary to the most obvious hypothesis, neither ALOX5 protein nor arachidonic acid
(AA)-derived LTB4, LTD4 and LTE4 varied by genotype.
However 5-hydroxyeicosatetraenoate (5-HETE), 6-trans-LTB4, 5-oxo-ETE, 15-HETE and 5,15-DiHETE were higher in subjects homozygous for the ALOX5 promoter allele containing 5 Sp1-element tandem repeats (“55” genotype, the “protective” geno-type) than in subjects with one “deletion” (3 or 4 repeats) and one common allele (“d5”) or with two deletion alleles ( “dd”). The EPA-derived metabolites 5-HEPE and 15-HEPE and the DHA-de-rived metabolite 17-HDoHE had similar associations with geno-type and increased with supplementation; 5-HEPE and 15-HEPE increased and 5-oxo-ETE decreased to a greater degree in the “55” than in the other genotypes. This differential eicosanoid re-sponse is consistent with the previously observed interaction of these variants with dietary intake of omega-3 fatty acids in pre-dicting cardiovascular disease risk and suggests that products different from the originally postulated leukotrienes, but rather hydroxyl and peroxy-fatty acids produced through 5-LO may mediate the pharmacogenetic effects reported previously. Re-search in anti-inflammatory, anti-atherogenic properties of the various eicosanoids increased in the “55” protective genotype, and increased further by fish oil, are now warranted.
PMID: 20950718
1. Abstract available from: http://www.ncbi.nlm.nih.gov/pubmed/21296957. Accessed 4/14/2012.
Resource Review: ALOX5 Gene Variants Affect Eicosanoid Production and Response to Fish Oil Supplementation
Resource Review
HOT Nutritional Genomics Research Publications
Courtesy of the International Society of Nutrigenetics and Nutrigenomics (ISNN), www.isnn.info/, and www.nutrigenetics.net.
Rare variants in the CYP27B1 gene are associated with mul-tiple sclerosis. Ann Neurol. 2011 Dec;70(6):881-6. doi: 10.1002/ana.22678.
Variants in the CYP27B1 gene such as Arg389His result in lower levels of calcitriol (1,25-dihydroxyvitamin D3). This may explain a gene-environment relationship which has been seen between lower levels of UV light and higher risk of multiple sclerosis. The authors conclude by suggesting that vitamin D supplementa-tion studies for prevention are “strongly warranted.”
Metabolic syndrome: Evidences for a personalized nutri-tion. Mol Nutr Food Res. 2012 Jan;56(1):67-76. doi: 10.1002/mnfr.201100531. Epub 2011 Nov 17. New research is beginning to reveal important gene-environment interactions that may be useful for prevention of metabolic syndrome by use of person-alized nutrition. Variants of the following genes are discussed: ADIPOQ, ADIPOR1, ADIPOR2, CAPN10, GCKR, TCF7L2, and LEPR.
Dietary flavonoids are neuroprotective through Nrf2-coordinat-ed induction of endogenous cytoprotective proteins. Nutr Neu-
rosci. 2011 Sep;14(5):226-36. Nrf2 (NFE2L2 gene) is emerging as an important regulator of neuroprotective gene expression resulting from dietary flavonoids. This may lead to novel com-plementary and alternative therapies for various neurological disorders, including strokes.
Black tea extract prevents lipopolysaccharide-induced NF-κB signaling and attenuates dextran sulfate sodium-induced exper-imental colitis. BMC Complement Altern Med. 2011 Oct 11;11:91. Black tea extract was found to reduce colon inflammation by blocking NF-kappaB signaling and apoptosis.
Vitamin D and cardiovascular disease. J Am Coll Nutr. 2011 Jun;30(3):167-70. Vitamin D regulates the expression of various genes, and deficiency of vitamin D is common. Growing evi-dence suggests that vitamin D is important for cardiovascular health, and that a deficiency may be a cardiovascular risk factor.
Genetic and nutritional interactions in cardiovascular dis-ease. World Rev Nutr Diet. 2011;102:150-5. Epub 2011 Aug 5. Nutrition plays a large role in modulating gene expression, and in influencing many of the modifiable risk factors associated with a first myocardial infarction. Variants in genes like ALOX5 and in APOA1 are mentioned as examples. The APOA5 -1131T-C variant is also described in some detail.
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NOS3 Glu298Asp polymorphism interacts with virgin olive oil phenols to determine the postprandial endothelial function in patients with the metabolic syndrome. J Clin Endocrinol Metab. 2011 Oct;96(10):E1694-702. Epub 2011 Aug 3. The Glu298Asp (or 894G-T) variant of NOS3 is considered a risk factor for hyper-tension and cardiovascular disease associated with endothelial dysfunction. In this study, subjects with metabolic syndrome who carry two copies of this variant were found to have lower postprandial levels of endothelial NOS. Most of this difference was reduced when high-phenol olive oil was used instead of low-phenol olive oil.
Lycopene inhibits NF-kB-mediated IL-8 expression and chang-es redox and PPARγ signalling in cigarette smoke-stimulated macrophages. PLoS One. 2011;6(5):e19652. Epub 2011 May 19. The anti-inflammatory action of lycopene in cells exposed to cigarette smoke is explored, with evidence of a mechanism in-volving the inactivation of NF-kappaB.
The impact of common gene variants on the response of bio-markers of cardiovascular disease (CVD) risk to increased fish oil fatty acids intakes. Ann Rev Nutr. 2011 Aug 21;31:203-34. This review article describes inconsistencies in response to di-etary omega-3 fatty acids, and provides an extensive listing and discussion of genes and gene variants which may be responsi-ble. More research is warranted in light of its “wide public health relevance.”
For inquiries about above references, contact Ron L Martin, MS, President, Nutrigenetics Unlimited, Inc.; [email protected]. Check out www.isnn.info/ and choose the “ISSN Application” but-ton to learn more about the Dietitians in Intergrative and Func-tional Medicine membership discount.
ISNN will be hosting a Pre-Congress, Introductory Workshop for Di-etitians, November 18, 2012 in Sao Paulo, Brazil. More information can be obtained from the ISNN website noted above.
Resource Review: HOT Nutritional Genomics Research Publications
Chair’s Corner: Kathy Moore, RD, CCN
Kathy Moore, RD, CCNDIFM Chair 2011-2012“Things may come to those who wait, but only the things left by those who hustle.”
---Abraham Lincoln, Sixteenth President of the United States
As this fiscal year for DIFM draws to a close, and my term as Chair ends, I have been reading a very inspiring
book, The Success Principles™, How to Get from Where You Are to Where You Want to Be, by Jack Canfield and Janet Switzer.
The quote above is in this book, in the Chapter called “Take Ac-tion”. I believe that this charge is so appropriate for our DIFM practice group and for our members. We have a lot at stake as we work to carve out the niche in the nutrition and healthcare world, establishing Integrative RDs as a valued and trusted re-source for guidance in integrative and functional nutrition. One of our first achievements was the publishing of our Standards of Practice and Standards of Professional Performance in June of 2011. Our application to the Council on Future Practice for Certi-fied Specialist Integrative and Functional Nutrition is now being refined for resubmission. It is critical for us to take action—now, and each and every day—to become well educated and highly experienced in our field, so that we earn the credibility and repu-tation that makes us the “go-to” professionals. This means that every member, and every RD who sees integrative nutrition as a key requirement in the holistic picture of health and healthcare, must “own” their desire to participate.
We really must hustle so that we have a position at the table. We can’t sit around and wait! Consumers are demanding this information and this care. Integrative RDs are uniquely poised to blend the art of whole foods and their nutrient components with the science of discovering one’s biochemical needs based on the individuality of nutritional genomics, lifestyle, and envi-ronment. Learning needs to be continual, as this fascinating ap-proach to health continues to unfold like the layers of an onion. So we must take action as a DPG and as individuals to make the education accessible, make it happen, and then apply the prin-ciples in practice to achieve the experience. Will you participate with us?
Your Executive Committee is working on the “big picture plans”. We have offered many valuable webinars this year. Other online training will be coming, as will a valuable pre-FNCE conference in Philadelphia. We welcome your input and suggestions; please send them by email to [email protected].
Thank you to the over 30 members who have worked diligent-ly throughout this year to move DIFM to action, to help us get “where we want to be”. It has been an honor to serve as your Chair this year.
In closing, consider this quote from John Ruskin, English author, art critic, and social commentator:
“What we think or what we know or what we believe is, in the end, of little consequence. The only consequence is what we do.” Let’s commit to TAKE ACTION!
Kathy Moore, RD, CCNDIFM Chair, 2011-2012
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The first day of spring has come and gone, but the season is in full bloom. Like the New Year, many people look
at spring as a time to start fresh or renew. Magazines on the racks beckon us to clean our house, our closets, and our lives of clutter and debris. This issue is not about cleansing our house but about cleansing or detoxing our bodies of the environmental and
physiological clutter and debris that we have gathered over the winter or over a lifetime. This issue of the DIFM newsletter will take you from basic liver physiology, to what a detox diet is and why it can be beneficial, to how to test for harmful compounds, to the correct and healthful way to detox. This will be one issue that members will want to keep as a reference for years to come.
Thinking of Spring and renewal, don’t forget to renew your dues for this valuable practice group if you have not already. Additionally, some of you have unsubscribed to the DIFM eblasts which are our means of communicating with our membership and the vehicle we use to send the DIFM newsletters. Please resubscribe to the DIFM mailing list, so you don’t miss out! To resubscribe, click this link http://visitor.r20.constantcontact.com/
manage/optin/ea?v=001zyOLoEKlyAZZbJk_JleM2Q%3D%3D and add your email address. If you have questions, contact Amy Jarck at [email protected].
As Editor, I always welcome your input and suggestions and encourage you to contact me at [email protected]. Comments, suggestions, and yes, criticisms are shared with our fantastic, diligent Executive Committee who are hard at work on credentialing for the Integrative RD.
I write this as I am listening to the birds, whom I have not heard for so long, sing and converse in the trees outside my office window. After ten years of desert living, Colorado beckoned once again and I returned to a place of seasons—and a healthier environment. Moving was the first step in my own process of detoxing and now I am ready to proceed on to the next by using the key steps and information from this issue to enhance my physiological health. This issue has been much like planting the garden I am planning. The seeds are here to be sown and if they are not planted, they will not grow. So as I put the finishing touches on this issue, I am looking forward to planting the seeds of knowledge gained in this issue as well as the seeds in my first real garden in years!
Editor’s Notes: Sarah Harding Laidlaw, MS, RD, MPA, CDE
SAVE THE DATE:
NUTRITIONAL GENOMICS INTRODUCTORY WORKSHOP 1PM-6PM Sunday, November 18, 2012 (São Paulo, Brazil)
Promoted by:International Society of Nutrigenetics/Nutrigenomics (ISNN)
Brazilian Food and Nutrition Society (SBAN) Dietitians in Integrative and Functional Medicine DPG (Dietetic Practice Group) of the American Academy of
Nutrition and Dietetics
6th ISNN Nutrigenetics and Nutrigenomics Congress November 18-21, 2012 (São Paulo, Brazil)
Please note, the Introductory Workshop has been designed specifically for dietitians and precedes the ISNN Congress, offering a wonderful opportunity to get updated on the latest developments in nutritional genomics.
Specific information can be found at http://www.isnnbrazil.org.br/.
The ISNN and Congress organizers are pleased to offer a 30% discount in registration fee for the VI ISNN Congress to the members of American Academy of Nutrition and Dietetics!
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EXECUTIVE COMMITTEE
Chair 2011-2012sKathy Moore, RD, LD, CCNPo Box 487 Tijeras, NM 87059-0487Phone: 505-286-2428 Cell: 505-410-1922Fax: [email protected]
Past Chair 2011-2012s Deborah Ford, MS, RD, CCN1031 S. Shannon StreetVan Wert, OH 45891-2548 Phone: [email protected]
Chair Elect 2011 - 2012Alicia Trocker, MS, RDs
4078 Black Bird WayCalabasas, California 91302Cell: 818-970-1990Fax: [email protected]
Treasurer 2010-2012Leslie Kay Getzinger, MS, RD s3147 Ferncreek Ln Escondido, CA 92027Phone: 714-454-1813Fax: 858-408-3318 [email protected]
Treasurer-Assistant 2011-2012Julie Starkel, MS, MBA, RD6329 20th Ave NESeattle, WA 98115-6909Phone: 206-729-5111Fax: 206-588-2625 Cell: 206-617-2729 [email protected]
Secretary 2011-2013 Erica Kasuli, MS, RDs
20 West 64th Street, Apt 35NOne Lincoln PlazaNY, NY 10023 Phone [email protected]
sIndicates Voting Member
Communications Chair 2011-2012Robin Foroutan, RD, HHC527 East 6th Street, #2W New York, NY 10009-6649 Cell: 917-453-2517 Phone: 212-677-7218 [email protected] Development Chair 2010-2012Lea Russell, MBA, RD, LDN605 20th Ave NESt Petersburg, FL 33704Phone: 727-822–[email protected]
Development Associate 2011-2012 Maryelaine Sotos, RD710 Colorado StreetApartment 7JAustin, TX 78701Phone: 512-474-2292Cell: [email protected]
DPG Delegate 2010-2013Ane Marie Kis, MS, RD, LDNPO Box 146Ardmore, PA 19003 - 0146Phone: 610-688-3990Cell: 610-453-1193 Fax: [email protected]
Executive Asst/Website Mgr/ EML Coordinator 2011-2012Amy Jarck 6 Juliana DrivePittsfield, MA 01201 Phone: 800-279-6880Cell: 413-448-1734 Fax: [email protected]
Website Editor- Associate 2011-2012 Emily D. Moore, RD, LDN202 Oak DriveMiddletown, DE 19709Phone: [email protected] Website Editor- Associate 2011-2012Sarah D’Emilio, RD, LDN923 Grosstown RoadStowe, PA 19464Phone: [email protected]
Fulfillment Chair 2011-2012 Angela B. Moore, MS, RD7150 E Berry Ave Greenwood Village, CO 80111 Phone: 720-201-1128 [email protected]@fitlifeofcolorado.com
Member Services Chair 2011-2012Jacki Glew, MS, RD, CSO, LDNClinical Nutrition ManagerBlock Center for Integrative Cancer Treatment5230 Old Orchard RdSkokie, IL 60077Phone 847-505-0822 Fax 847-505-0822Cell [email protected]
Member Services Chair – Associate 2011-2012Christine Doolittle MS, RD, CSSD, LDN, CLT730 Bridle Path DriveWexford, PA 15090-6815Phone: 724-272-6351Fax: [email protected]
Network Chair 2011-2012 Kathie Madonna Swift, MS, RD, LDN248 Mountain DrivePittsfield, MA 01201Phone: 413-238-1421Fax: [email protected]
Network Associate 2011-2012Lisa L Powell, MS, RD8110 E Rockgate RdTucson, AZ 85750-9735Phone: 520-749-9655Fax: [email protected]
Network Associate 2011-2012Melinda Dennis227 Coolidge Ave Apt 209Watertown, MA 02472-1550 Phone: [email protected]
Newsletter Editor 2011-2012Sarah Harding Laidlaw, MS, RD, MPA, CDE60870 Kansas Road Montrose, CO 81403 Phone: 970-216-2356 Fax: [email protected]
Newsletter Editor-Associate 2011-2012Jacqueline Santora Zimmerman, MS, RD41 West Hitchcock AveFloral Park, NY 11001Phone: [email protected]
Newsletter Copy Editor 2011-2012 Emily D. Moore, RD, LDN202 Oak DriveMiddletown, DE 19709Phone: [email protected]
Newsletter CPE editor Shari B Pollack, MPH, RD4500 Keeney St.Skokie, IL 60076Phone: 847-213-0424Fax: [email protected]
Newsletter CPE Item WriterJanelle L’Heureux, MS, RD10920 Fairbanks WayCulver City, CA 90230Phone: 213-201-1556 Cell: [email protected]@gmail.com
Newsletter Resource Reviews Editor Barbara Goldman MS, CDE, LDN, RD163 Pennock Trace Dr Jupiter, FL 33458-7577Phone: 561-575-1256 [email protected]
Nominating Committee Chair 2011-2012 Marlisa Brown, MS, RD, CDE, CDN 160 Howells Rd, Suite 6Bay Shore, NY 11706-5320 Phone: 631-666-4297 Cell: 631-987-9406 Fax: 631-666-5284 [email protected] Nominating Committee Chair Elect 2011-2012 Diana Noland, MPH, RD, CCN9018 Balboa Blvd #535 Northridge, CA 91325 Phone: 818-606-8457 Fax: 818-895-2454 [email protected]
Nominating Committee Member 2011-2012Stephen J Roch Jr., RD, LDN, CFT 3716 Page Dr Metairie, LA 70003Phone: 504-455-5813 [email protected]
Nutritional Genomics Advisor 2011-2013Colleen Fogarty Draper, MS, RD, LDN7 High Rock RoadStoneham, MA 02180-2869Phone: 781-438-4749Cell: 617-680-3082Fax: [email protected]
Professional Advancement Chair 2010-2012 Elizabeth Redmond, PhD, MS, RD, LD2312 Spring Creek RoadDecatur, GA 30033Phone: 678-638-2954Cell: [email protected]
Professional Advancement Associate 2010-2012Esther Trepal, RD, MS, CDN God’s Love We Deliver 166 Avenue of the Americas New York, NY 10013Phone: 212-294-8165Cell: 646-831-1613Fax: 212-294-8139 [email protected] Public Policy/Reimbursement Chair 2011-2013Rita Kashi Batheja, MS, RD, CDN825 Van Buren StreetBaldwin Harbor, NY 11510Phone: 516-868-0605Cell: [email protected]
Student Committee Chair 2011-2013Monique M Richard1752 Red Jacket Dr.Antioch, TN 37013Phone: 615-781-6762Cell: [email protected]
DIFM Credentialing Task Force Co-Chair 2011Lisa A Dorfman, LMHC, MS, RD, CSSDPO BOX 565505Miami, FL 33256-5505Phone: 305-854-1065Cell: [email protected]@miami.edu
DIFM Credentialing Task Force Co-Chair 2011Mary Beth Augustine CDN, RD10 Nancy RoadBrewster, NY 10509Phone: 845-278-0530Cell: [email protected]@gmail.com
Technical Advisor 2011-2013Ruth DeBusk, PhD, RDDeBusk Communications, LC3583 Doris DriveTallahassee, FL 32303-2304Phone/Fax: [email protected]
Academy Practice Manager 2011-2012 Carrie KileyManager, DPG/MIG/Affiliate RelationsThe Academy of Nutrition and Dietetics120 S. Riverside Plaza Suite 2000Chicago, IL 60606-6995Phone: 800-877-1600 x 4778 Fax: 312-899-4778 [email protected]
DIFM Office Address Dietitians in Integrative and Functional Medicine P.O. Box 3624Pittsfield, MA 01202Phone: 800-279-6880 Fax: 877-862-8390 email address: [email protected]: www.integrativerd.org
Revised March 12, 2012
2011 - 2012 LEADERSHIP CONTACT INFORMATION
100
THANK YOU TO OUR SPONSORSWithout your generous contributions, many of the opportunities
and member benefits would not be possible.
Titanium
Platinum
Editor
Sarah Harding Laidlaw, MS, RD, CDE
Associate Editor
Jacqueline Santora Zimmerman, MS, RD
Copy Editor
Emily D. Moore, RD, LDN
CPE Editor
Shari B. Pollack, MPH, RD
Communications Chair
Robin Foroutan, RD, HCC
Editors
Christian Calaguas, MPH, RD
Danielle Torisky, PhD, RD
Newsletter CPE Item Writer
Janelle l’Heureux, MS, RD
The views expressed in this newsletter are those of the authors and do not necessarily reflect the policies and/or official positions of the Academy of Nutrition & Dietetics.We invite you to submit articles, news and comments. Contact us for author guidelines.Send change-of-address notification to the Academy of Nutrition & Dietetics, 120 South Riverside Plaza, Ste. 2000, Chicago, IL 60606-6995.Copyright © 2011 Dietitians in Integrative and Functional Medicine, a Dietetic Practice Group of the Academy of Nutrition & Dietetics. All material appearing in this newsletter is covered by copyright law and may be photocopied or otherwise reproduced for noncommercial scientific or educational purposes only, provided the source is acknowledged. For all other purposes, the written consent of the editor is required.
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DIFM EDITORIAL STAFF
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