1. No category

International Journal of Human Nutrition and Functional Medicine www.ICHNFM.org
Villa de Leyva, Colombia (2014)
Editorial • Essay • Perspective
A Brief Case against "Omics" and "Precision Medicine"
as the Future of Functional Medicine
Consideration of Priorities, Profiteering, Scientific Positivism, Class Privilege,
and Old Trustworthy Dogs versus New Expensive and Unproven Tricks
Alex Vasquez DC ND DO FACN
What is "Omics", precision medicine, and how do these relate to clinical practice? Who will benefit?
The English-language neologism "omics" refers to any of several fields of study in biology ending in -omics, such as
genomics, proteomics or metabolomics; the term can also be used to discuss these disciplines as a grouped whole. Each
of these fields focuses on what might be called its respective physiologic compartment or sector, such as the genome,
proteome or metabolome. Omics is basically the science of identifying and characterizing patterns of biological
molecules and their health/disease associations so that patterns of response can be appreciated, and then—theoretically—
understood and therapeutically manipulated. What I provide in this essay are perspectives and proposals to discourage
and deflate the rising hyperbole surrounding –omics.
My first editorials related to omics were written and published inn 2006 specific to the conversation of the
medical profession's hyperfocus on "molecular medicine" and the related and resultant dream of pharmacogenomics—
for convenience and perspective, those original editorials have been appended to this current one.
What is scientific positivism?
Scientific positivism is an intellectually justified psychological "bait and switch" technique to distract us into focusing
onto an imagined more positive future so that we can ignore the discomforts of our present reality.
My first encounter of and use here of the term scientific positivism stems from the following passage from Friedrich
Nietzsche's 18XX book written in German titled Fröhliche Wissenschaf conveniently and generally translated as Gay
Science but which would have been more accurately translated as The Science of Happiness or Joyful Knowledge.
Updates: The most complete version of this article is available at the following location http://intjhumnutrfunctmed.org/
Copyrights: Copyright © 2015 by author(s) and International College of Human Nutrition and Functional Medicine www.ICHNFM.org
Citation: Vasquez A. The case against -omics as the future of functional medicine. Int J Hum Nutr Funct Med 2015:3(1);2
"Some have still need of metaphysics; but also the impatient longing for certainty which at present discharges itself in
scientific, positivist fashion among large numbers of the people, the longing by all means to get at something stable
(while on account of the warmth of the longing the establishing of the certainty is more leisurely and negligently
undertaken): even this is still the longing for a hold, a support; in short, the instinct of weakness, which, while not
actually creating religions, metaphysics, and convictions of all kinds, nevertheless preserves them. In fact, around all
these positivist systems there fume the vapours of a certain pessimistic gloom, something of weariness, fatalism,
disillusionment, and tear of new disillusionment or else manifest animosity, ill humour, anarchic exasperation, and
whatever there is of symptom or masquerade of the feeling of weakness. Even the readiness with which our cleverest
contemporaries get lost in wretched corners and alleys, for example, in Patriotism (I mean what is called chauvinisme
in France and "deutsch" in Germany), or in petty aesthetic creeds in the manner of Parisian naturalisme. (which only
brings into prominence and uncovers that aspect of nature which excites simultaneously disgust and astonishment they
like at present to call this aspect la verite vraie), or in Nihilism in the St Petersburg style (that is to say, in the belief in
unbelief, even to martyrdom for it): this shows always and above all the need of belief, support, backbone, and
buttress. Belief is always most desired, most pressingly needed, where there is a lack of will: for the will, as the affect
of command, is the distinguishing characteristic of sovereignty and power. That is to say, the less a person knows how
to command, the more urgent is his desire for that which commands, and commands sternly, a God, a prince, a caste, a
physician, a confessor, a dogma, a party conscience.
http://www.lexido.com/EBOOK_TEXTS/THE_GAY_SCIENCE_FIFTH_BOOK_.aspx?S=347
Here's my take on IFM's "omics" = impractical, too expensive, and founded on white priveledge and scientific
positivism
plus avoids dealing with REALITY and problems we can solve without technology
International Journal of Human Nutrition and Functional Medicine www.IntJHumNutrFunctMed.Org 2014 final PDF
International Journal of Human Nutrition and Functional Medicine www.IntJHumNutrFunctMed.Org 2014 final PDF
we must also note the paradox of prioritizing technology over human judgement and interaction, and then calling this
"personalized medicine"
What societal, national, and international health priorities are we avoiding by focusing on omics?
xxx.
Old dogs & new tricks
xxx.
What is the best approach?
xd.
In these days of social extremism, wherein rational dialoug had been replaced with black-and-white polarities that
defie logic, compromise, and consideration have infected and degerated conversations in healthcare ("") and politics
("You are either with us or against us.")
This is a general cases against futurist technology-dependent medicine. Notice that I used the word futurist and not
futuristic.
International Journal of Human Nutrition and Functional Medicine www.IntJHumNutrFunctMed.Org 2014 final PDF
the genome, proteome or metabolome
Reprint Molecular Cell Biology and Interventional Proteogenomics—Part One: The Proposed Future of
Allopathic Medicine
This Editorial was originally printed in Naturopathy Digest
naturopathydigest.com/archives/2006/oct/editor.php
By Alex Vasquez, ND, DC, Editor, Naturopathy Digest
[email protected]
The consensus in allopathic medicine these days is that "the age of molecular medicine" clearly is upon us and will be
the dominant paradigm for assessment and treatment of patients for the foreseeable future. More and more allopathic
medical schools are requiring undergraduate work in molecular cell biology as a prerequisite to application, and the
course curricula of many allopathic/osteopathic colleges is heavily focused on molecular biology and molecular
mechanisms of disease during the basic science portion of the first year. This trend toward the "molecularization" of
patients is a continuation of the pharmaceuticalization of patients that began some 60 years ago (approximate), when
the dominant paradigm in health care was translocated (with generous assistance from the drug companies) from
physiology to pharmacology.
Pharmacogenomics and proteogenomics grew from advancements in knowledge, spurred on by both the technological
advances that have facilitated the elucidation of the molecular/genetic aspects of diseases and the superabundance of
data collected from the Human Genome Project. To what extent these intellectual advances and informational
acquisitions translate into improved patient care and societal health remains to be seen, though some legitimate
breakthroughs already have been harvested.
Utilization/exploitation of this data and its associated technology is, of course, a paramount priority for pharmaceutical
corporations and biotechnology manufacturers who want to be the first on the market with new drugs and diagnostics,
respectively. What might be called "futuristic" by the pharmaco-allopathic camp might be seen as "dehumanizing" or
perhaps "horrific" from a naturopathic perspective. Herein lies a challenge in reconciliation, as we as naturopathic
physicians and educators must be discerning enough to not throw this new biotechnological baby out with its
proverbial bathwater.
During my admittedly limited perusal of the literature on this topic on and off over the past few years, the articles of
Alan Roses, MD (from drug giant Glaxo Wellcome) have stood out as perhaps being exemplary of the direction some
would like to see medicine take. The image conjured is one in which a patient submits a DNA and/or protein sample so
a computer-linked diagnostic test can be performed, which then provides the doctor a list of appropriate drugs, drug
contraindications and drug combinations, which are then prescribed. This, as Dr. Roses notes, will not only take much
of the art out of health care, since judgment will be supplanted by technological accuracy1, but, as I note, also will take
the humanity out of health care, as patients are reduced to a computer-generated readout translating into a shopping list
for drugs.
1
"Through the use of pharmacogenetics, we will soon be able to profile variations between individuals' DNA to predict responses to
a particular medicine. ... [This] will provide information on the likelihood of efficacy and safety of a drug for an individual patient, will
change the practice and economics of medicine." Roses AD. Pharmacogenetics and the practice of medicine. Nature 2000 Jun
15;405(6788):857-65.
International Journal of Human Nutrition and Functional Medicine www.IntJHumNutrFunctMed.Org 2014 final PDF
To the extent that such diagnostic data can be used to predict adverse drug effects (which, along with other doctor
errors, kill about 3,500 Americans per week2), I think we will all agree it does reflect an advancement in health care.
However, to the extent that such "personalized" data is interpreted/applied in such a way as to "depersonalize" the
patient, who is then nothing more than a collection of genes and gene products, then it's antithetical to holism in
general and naturopathy in particular; it's the medical affirmation of genetic determinism. The two paradigms
contained within the advocation of pharmacogenomics are that: 1) diseases are caused (predominately) by defective
genes; and 2) the appropriate treatments for diseases are drugs that interfere with the processes affected by those
defective genes and their post-translational products. Dr. Roses proposes that the patient will be assessed/measured by
submission of samples to the diagnostic testing equipment, that this raw data will be fed into a computer linked to the
Physician's Desk Reference (i.e., a compilation of drug advertisements) and a list of drugs will be printed from which
the physician will select and that the patient will purchase. The assessment of the patient and the formulation of the
treatment plan appear as this, per Roses3, "The patient's micro disk containing his standard genome variations profile
(SGVP), as well as other personal medical and financial profiles, is inserted into the electronic Physician's Desk
Reference Reader linked to the updated database for pharmacogenetic data, covering adverse events and efficacy data
for all medicines registered."
Yeow! How would you like to be a patient and have your treatment plan and your personal future decided for you by a
lab test exclusively tied to drug advertisements? Don't worry, you won't be reduced to only your genes; note that part
of the assessment also includes your "financial profile." Take a few minutes to think about that!!
In next month's editorial, we'll see if we can find a light at the end of this geno-deterministic, pharmaco-financial
tunnel. Is there a bright side of this for naturopathic medicine; are there implications for the immediate future of
naturopathic medical education? I think so. Stay tuned.
Reprint Molecular Cell Biology and Interventional Proteogenomics—Part Two: From Biological Science
to the Possibilities of Pharmacoeconomic Misappropriation
This Editorial was originally printed in Naturopathy Digest
naturopathydigest.com/archives/2006/nov/editor.php
Whether the genomic revolution and the advancing science of molecular cell biology will serve as menaces or
opportunities for the naturopathic profession depends upon the ways in which these sciences and their associated
assessments and interventions are applied clinically, socially and politically, as I began to discuss in the first of this
three-part series. The suggestion that patient assessment and treatment eventually could hinge on the triad of 1)
laboratory tests; 2) financial status; and 3) genomic analysis4, might seem so repulsive that we could be tempted to
discard clinical genomics prima facie and thus potentially deny ourselves and our patients the benefits that might lie
within these rapidly progressing sciences.5
The "central dogma of molecular biology," which you can find in most modern biochemistry textbooks,6 states
that information encoded within DNA is transcribed to mRNA and then translated into proteins that are biologically
active and which then allow for and orchestrate physiologic processes. If those processes are appropriate and well
orchestrated, health is the result. But if the DNA is mutated, the transcription is flawed or the translation is defective,
then the orchestra of organelles and physiologic processes and responses will be out of tune, resulting in poor health, at
best, and overt disease, at worst. Thus, according to current and widely accepted basic science textbooks used in
2
"Recent estimates suggest that each year more than 1 million patients are injured while in the hospital and approximately 180,000
die because of these injuries. Furthermore, drug-related morbidity and mortality are common and are estimated to cost more than
$136 billion a year. The most common type of drug-induced disorder is dose-dependent and predictable." Holland EG, Degruy FV.
Drug-induced disorders. Am Fam Physician 1997 Nov 1;56(7):1781-8, 1791-2
3 Roses AD. 2025: The practice of neurology: back from the future. Arch Neurol 2001 Nov;58(11):1766-7
4 Roses AD. 2025: The practice of neurology: back from the future. Arch Neurol 2001 Nov;58(11):1766-7
5
Cooper and Hausman. The Cell: A Molecular Approach, Fourth Edition.
6 Champe PC, Harvey RA, Ferrier DR. Lippincott's Illustrated Reviews: Biochemistry (Lippincott's Illustrated Reviews Series).
Lippincott 2004
International Journal of Human Nutrition and Functional Medicine www.IntJHumNutrFunctMed.Org 2014 final PDF
medical schools, defective genes and/or defective gene products generally result in dysfunction and disease. While
some defects are either mild or completely subclinical, many others are - sooner or later - a danger to health and life.
The misappropriation of this science, ripe for pharmacoeconomic exploitation, arises from a simple and subtle
reversal of the sequence of what is otherwise a basic science truism. The science states, "Defective genes or defective
gene products result in disease." Exploitation of this science states, "Disease results from defective genes or gene
products." Read those statements again if you need to; they appear similar but are powerfully different, and the
confusion of the former with the latter is what mutates science into pseudoscience.
Again, while we note the subclinical and subpathologic exceptions, we must agree that if the severity and
importance are of a given sufficient magnitude, the defective genes or defective gene products will indeed result in
dysfunction, at best, and disease, at worst. Examples of this truism include sickle cell anemia (caused by a DNA point
mutation that results in the insertion of valine in place of glutamic acid in the betaglobulin chain of hemoglobin) and
cystic fibrosis (caused by homozygous gene mutations, often resulting in an absence of phenylalanine from the CFTR
protein). Indeed, defective genes can result in defective proteins that impair normal function and cause disease, as
these simplistic and stereotypical examples illustrate.
But, when this same linearity is applied to the disorders commonly encountered in clinical practice (such as
obesity, hypertension, diabetes, depression and the autoimmune diseases), the vast majority of which are
multifactorial, we can see how a subtle modification of a well-established truism can fool doctors and patients alike
into believing the common chronic illness they are dealing with is the primary result of defective genes, for which the
appropriate treatment is a gene-specific pharmaceutical drug.
The stronger the gene-disease link appears in the research, the easier it will be to convince doctors and patients
that drugs should be used for the treatment of those diseases, especially those still codified as "idiopathic" within the
medical community. Transitioning from "idiopathic" to "genetic" carries the same therapeutic implications: Generally,
it results in a situation in which the patient is disempowered and forced to rely on some exogenously administered drug
for the treatment/amelioration/suppression of their condition. Again, in situations in which a drug can effectively,
completely, safely and affordably treat a given disease caused by a gene defect, such a drug certainly is an appropriate
consideration and might even be the treatment of choice. However, what happens more often, and what is happening
on a progressively larger and larger scale, is that subcurative drugs are being used either as monotherapy or in
conjunction with other subcurative drugs ("polypharmacy"), simply because a gene association has been identified and
this "association" was later mutated into a "causative association" by pharmaceutical companies that have tied their
drugs to the links between diseases and various gene defects.
As genomic testing becomes more widely used and as the drug companies focus on linking their drugs with
genes (rather than only diseases, as was previously the case), the finding of an associated gene in a patient with a
specific disease will be interpreted to mean that the gene-disease relationship is causal and the gene-specific drug is the
appropriate treatment. This already occurs today, even when the disease is predominately lifestyle- and environmentinduced (e.g., diabetes). The marketing slogan and treatment mantra is, "If you have a disease, it's because you have
bad genes, and you need this drug specific for your genes and your disease if you want to survive your disease." This
paradigm of genetic determinism, coupled with pharmacologic salvation, increasingly is well engrained in our
conceptualizations of nearly all major chronic diseases, and the list of diseases associated with, and therefore, assumed
to be caused by gene defects grows every day. When misappropriated, genomic tests will serve as a fulcrum with
which to propel the sale of pharmaceutical drugs into the high-profit stratosphere. Conversely, genomics could be a
golden opportunity for naturopathic medicine, and this is what we will explore in the next and final article in this
series.
Reprint Molecular Cell Biology and Interventional Proteogenomics—Part Three: New Implications for
Naturopathic Medical Education, Clinical Practice and Naturogenomics
This Editorial was originally printed in Naturopathy Digest
naturopathydigest.com/archives/2006/dec/editor.php
Nothing will stop the advancement of genomic medicine, and perhaps nothing should. At its best, genomic medicine
simply is the clinical application of genomics and the data and insights gleaned from the rapidly advancing basic
science of molecular biology.
International Journal of Human Nutrition and Functional Medicine www.IntJHumNutrFunctMed.Org 2014 final PDF
What remains to be seen is the extent to which this information is either utilized to advance patient care or the
extent to which it's exploited for pharmacoeconomic profitability1 and subsequent indirect and direct suppression of
naturopathic medicine and hindrance of patient care.2
Medical journals, medical associations, and the medical profession as a group (minor exceptions noted) can be
expected to acquiesce to the dictums of the pharmaceutical industry since this private industry controls much of the
research and many of the major medical journals (according to the recent editors of the New England Journal of
Medicine,3 British Medical Journal,4 and The Lancet5). The general population of patients is likewise influenced by
the pharmaceutical industry via direct-to-consumer advertising, which represents the vast majority of their "health
education" in the form of drug advertisements that entice wanton and additive drug consumption.6 As naturopathic
physicians are the only doctorate-level clinicians educated to use nutrition, lifestyle and treatment of the underlying
problem before turning to drugs, it seems probable that if any "balance" to the clinical application of genomics is to be
realized, then it might have to come from the ND perspectives. If this is true, then we must at least consider the
following two questions:
Is there a counterbalancing scientific basis supporting the use of botanical, nutritional and other "naturopathic"
interventions for diseases attributed to genomic defects and adverse patterns of gene expression?
Are naturopathic students in general, and the profession as a whole, aware of and current with the modern state
of the art in molecular cell biology,7 which includes the basic science of gene expression and the means by which a
potentially healthy geneotype is transformed into a disease-ridden phenotype?
The answer to the first question in general is "yes" but it must be applied on a disease-by-disease and case-bycase basis. Generally, most of our nutritional/botanical/naturopathic therapeutics have an effect on gene expression as
part of the mechanism by which their clinical benefits are realized. One important and common example I reviewed
previously8 is the downregulation of NF-kappaB activity effected by the use of routine therapeutics such as vitamin
D,9 lipoic acid,10 green tea,11 rosemary,12 grape seed extract,13 resveratrol,14 caffeic-acid-phenethyl-ester (CAPE)
from bee propolis,15 indole-3-carbinol,16 N-acetyl-L-cysteine,17 selenium18 and zinc.19 The scope and length
limitations of this current article prohibit me from adding more examples, but it should suffice to say that the majority
of nutrients, botanicals and other natural interventions are effective in small or large part due to their effects on gene
expression. This leads us to the second question: Are naturopathic students in general, and the profession as a whole,
aware of and current with the modern state of the art in molecular cell biology?
I propose here that, although it should not supersede the importance of clinical outcome studies, the science of
molecular biology needs to take a more preeminent role in naturopathic education for the following reasons. First, like
it or not, molecular biology will be the language of the next edition of The King's English, published in journals and
underwritten by the pharmacomedical consortium. For the sake of interprofessional communication and keeping pace
with current and future research literature, NDs need to be fluent not only in the basics of transcription and translation,
but in the details of how these processes are effected by spliceosomes and (vitamin-induced) histone modification and
modulated by transcription factors, only one of which is NF-kapppaB. Second, for our own sake, in order to have a
more complete understanding of the mechanisms by which our treatments work, we need to delve deeper into the
science that details these effects. Third, as the naturopathic profession continues to take on larger and more important
roles in national health care, it's no longer sufficient to simply say, "It works;" we have to be able to accurately
describe mechanisms of effectiveness if we are to be on scientific par with our propharmaceutical counterparts.
Every time you make a dietary recommendation for a patient, you are changing his or her genetic expression
and inclination or aversion to disease;20 the modulation of genetic expression via natural/naturopathic interventions,
what I have termed "naturogenomics", is inclusive of nutrigenomics21 but differentiated from pharmacogenomics. The
recent finding that chronic neuropathic pain changes gene expression22,23 opens the door to new horizons for the
chiropractic profession and all of us who use manual, nutritional and botanical medicine in the alleviation of pain and
inflammation, but these and other opportunities will only be available to the profession as a whole if the profession as
a whole works to integrate this and other data on genetic expression and its modulation into our current research
projects, educational standards and clinical protocols. Properly utilized, molecular biology and the insights gleaned
from genomic testing hold scientific and clinical and therefore political promise for the naturopathic profession.
References
International Journal of Human Nutrition and Functional Medicine www.IntJHumNutrFunctMed.Org 2014 final PDF
•
•
•
•
•
•
•
•
•
•
•
•
See the following citations for examples: Roses AD. 2025: the practice of neurology: back from the future.
Arch Neurol 2001 Nov;58(11):1766-7; Angell M. The Truth About the Drug Companies: How They Deceive
Us and What to Do About It. Random House; August 2004; Smith R. Medical journals are an extension of the
marketing arm of pharmaceutical companies. PLoS Med. 2005 May;2(5):e138. Epub 2005 May 17. Click to
view it online; "...despite lush advertisements from companies with obvious vested interests, and authoritative
testimonials from biased investigators who presumably believe in their own work to the point of straining
credulity and denying common sense... (translate: economic improvement, not biological superiority)."
Stevens CW, Glatstein E. Beware the Medical-Industrial Complex. Oncologist 1996;1(4):IV-V. Click to
download PDF.
See the following citations for examples: Wilk CA. Medicine, Monopolies, and Malice: How the Medical
Establishment Tried to Destroy Chiropractic. Garden City Park: Avery, 1996; Carter JP. Racketeering in
Medicine: The Suppression of Alternatives. Norfolk: Hampton Roads Pub; 1993; Morley J, Rosner AL,
Redwood D. A case study of misrepresentation of the scientific literature: recent reviews of chiropractic. J
Altern Complement Med. 2001 Feb;7(1):65-78; Micozzi MS. Double standards and double jeopardy for CAM
research. J Altern Complement Med. 2001 Feb;7(1):13-4; Terrett AG. Misuse of the literature by medical
authors in discussing spinal manipulative therapy injury. J Manipulative Physiol Ther. 1995 May;18(4):20310.
Angell M. The Truth about the Drug Companies: How They Deceive Us and What to Do About It. Random
House; August 2004.
Smith R. Medical journals are an extension of the marketing arm of pharmaceutical companies. PLoS Med.
2005 May;2(5):e138. Epub 2005 May 17. Click to view it online.
Op cit: "Journals have devolved into information laundering operations for the pharmaceutical industry."
Horton R. The Dawn of McScience. New York Rev Books. 2004;51(4):7–9. Click to view it online.
"...many ads may be targeted specifically at women and older viewers. Our findings suggest that Americans
who watch average amounts of television may be exposed to more than 30 hours of direct-to-consumer drug
advertisements each year, far surpassing their exposure to other forms of health communication." Brownfield
ED, Bernhardt JM, Phan JL, Williams MV, Parker RM. Direct-to-consumer drug advertisements on network
television: an exploration of quantity, frequency, and placement. J Health Commun. 2004 Nov-Dec;9(6):4917.
Cooper and Hausman: The Cell: A Molecular Approach, Fourth Edition. ISBN 9780878932191,
www.sinauer.com/detail.php?id=2191. See also www.sinauer.com/cooper/4e/ for samples and animations.
Vasquez A. Reducing Pain and Inflammation Naturally - Part 4: Nutritional and Botanical Inhibition of NFkappaB, the Major Intracellular Amplifier of the Inflammatory Cascade. A Practical Clinical Strategy
Exemplifying Anti-Inflammatory Nutrigenomics. Nutritional Perspectives 2005; July: 5-12. Click to view it
online.
"1Alpha,25-dihydroxyvitamin D3 (1,25-(OH)2-D3), the active metabolite of vitamin D, can inhibit NFkappaB activity in human MRC-5 fibroblasts, targeting DNA binding of NF-kappaB but not translocation of
its subunits p50 and p65." Harant H, Wolff B, Lindley IJ. 1Alpha, 25-dihydroxyvitamin D3 decreases DNA
binding of nuclear factor-kappaB in human fibroblasts. FEBS Lett. 1998 Oct 9;436(3):329-34.
"ALA reduced the TNF-alpha-stimulated ICAM-1 expression in a dose-dependent manner, to levels observed
in unstimulated cells. Alpha-lipoic acid also reduced NF-kappaB activity in these cells in a dose-dependent
manner." Lee HA, Hughes DA.Alpha-lipoic acid modulates NF-kappaB activity in human monocytic cells by
direct interaction with DNA. Exp Gerontol. 2002 Jan-Mar;37(2-3):401-10.
"In conclusion, EGCG is an effective inhibitor of IKK activity. This may explain, at least in part, some of the
reported anti-inflammatory and anti-cancer effects of green tea." Yang F, Oz HS, Barve S, de Villiers WJ,
McClain CJ, Varilek GW. The green tea polyphenol (-)-epigallocatechin-3-gallate blocks nuclear factor-kappa
B activation by inhibiting I kappa B kinase activity in the intestinal epithelial cell line IEC-6. Mol Pharmacol.
2001 Sep;60(3):528-33.
"These results suggest that carnosol suppresses the NO production and iNOS gene expression by inhibiting
NF-kappaB activation, and provide possible mechanisms for its anti-inflammatory and chemopreventive
action." Lo AH, Liang YC, Lin-Shiau SY, Ho CT, Lin JK. Carnosol, an antioxidant in rosemary, suppresses
inducible nitric oxide synthase through down-regulating nuclear factor-kappaB in mouse macrophages.
Carcinogenesis. 2002 Jun;23(6):983-91.
International Journal of Human Nutrition and Functional Medicine www.IntJHumNutrFunctMed.Org 2014 final PDF
•
•
•
•
•
•
•
•
•
•
•
"Constitutive and TNFalpha-induced NF-kappaB DNA binding activity was inhibited by GSE at doses > or
=50 microg/ml and treatments for > or =12 h." Dhanalakshmi S, Agarwal R, Agarwal C. Inhibition of NFkappaB pathway in grape seed extract-induced apoptotic death of human prostate carcinoma DU145 cells. Int J
Oncol. 2003 Sep;23(3):721-7.
"Resveratrol's anticarcinogenic, anti-inflammatory, and growth-modulatory effects may thus be partially
ascribed to the inhibition of activation of NF-kappaB and AP-1 and the associated kinases." Manna SK,
Mukhopadhyay A, Aggarwal BB. Resveratrol suppresses TNF-induced activation of nuclear transcription
factors NF-kappa B, activator protein-1, and apoptosis: potential role of reactive oxygen intermediates and
lipid peroxidation. J Immunol. 2000 Jun 15;164(12):6509-19.
"Caffeic acid phenethyl ester (CAPE) is an anti-inflammatory component of propolis (honeybee resin). CAPE
is reportedly a specific inhibitor of nuclear factor-kappaB (NF-kappaB)." Fitzpatrick LR, Wang J, Le T.
Caffeic acid phenethyl ester, an inhibitor of nuclear factor-kappaB, attenuates bacterial peptidoglycan
polysaccharide-induced colitis in rats. J Pharmacol Exp Ther. 2001 Dec;299(3):915-20.
Takada Y, Andreeff M, Aggarwal BB. Indole-3-carbinol suppresses NF-{kappa}B and I{kappa}B{alpha}
kinase activation causing inhibition of expression of NF-{kappa}B-regulated antiapoptotic and metastatic gene
products and enhancement of apoptosis in myeloid and leukemia cells. Blood. 2005 Apr 5; [Epub ahead of
print].
Paterson RL, Galley HF, Webster NR. The effect of N-acetylcysteine on nuclear factor-kappa B activation,
interleukin-6, interleukin-8, and intercellular adhesion molecule-1 expression in patients with sepsis. Crit Care
Med. 2003 Nov;31(11):2574-8.
Faure P, Ramon O, Favier A, Halimi S. Selenium supplementation decreases nuclear factor-kappa B activity in
peripheral blood mononuclear cells from type 2 diabetic patients. Eur J Clin Invest. 2004;34(7):475-81.
Uzzo RG, Leavis P, Hatch W, Gabai VL, Dulin N, Zvartau N, Kolenko VM. Zinc inhibits nuclear factor-kappa
B activation and sensitizes prostate cancer cells to cytotoxic agents. Clin Cancer Res. 2002;8(11):3579-83.
Trujillo E, Davis C, Milner J. Nutrigenomics, proteomics, metabolomics and the practice of dietetics. J Am
Diet Assoc. 2006 Mar;106(3):403-13.
Kaput J, Rodriguez RL. Nutritional genomics: the next frontier in the postgenomic era. Physiol Genomics.
2004 Jan 15;16(2):166-77.
Rodriguez Parkitna J, et al. Comparison of gene expression profiles in neuropathic and inflammatory pain. J
Physiol Pharmacol. 2006 Sep;57(3):401-14.
Wang H, Sun H, Della Penna K, Benz RJ, Xu J, Gerhold DL, Holder DJ, Koblan KS. Chronic neuropathic
pain is accompanied by global changes in gene expression and shares pathobiology with neurodegenerative
diseases. Neuroscience. 2002;114(3):529-46.
International Journal of Human Nutrition and Functional Medicine www.IntJHumNutrFunctMed.Org 2014 final PDF