Elimination of persistent toxicants
from the human body
Stephen J Genuis
There is compelling evidence that various chemical agents are important determinants of myriad health
afflictions – several xenobiotics have the potential to disrupt reproductive, developmental, and neurological
processes and some agents in common use have carcinogenic, epigenetic, endocrine-disrupting, and
immune-altering action. Some toxicants appear to have biological effect at miniscule levels and certain chemical
compounds are persistent and bioaccumulative within the human body. Despite escalating public health mea-
sures to preclude further exposures, many people throughout the world have already accrued a significant
body burden of toxicants, placing them at potential health risk. As a result, increasing discussion is underway
about possible interventions to facilitate elimination of persistent toxicants from the human organism in order
to obviate health affliction and to potentially ameliorate chronic degenerative illness. An overview of the clinical
aspects of detoxification is presented with discussion of established and emerging interventions for the elim-
ination of persistent xenobiotics. Potential therapies to circumvent enterohepatic recirculation and a case
report highlighting a clinical outcome associated with detoxification are also presented for consideration.
bile acid sequestrants, chelation, cholestyramine, colon cleansing, detoxification, dialysis, enterohepatic
circulation, environmental medicine, fasting, massage, plasmapheresis, phlebotomy, probiotics, saponin
compounds, sauna therapy, toxicology, zeolites
Since the Second World War, tens of thousands of
synthetic compounds have been prepared and intro-
duced into the environment to facilitate many indus-
trial, domestic, and personal practices. With lack of
forethought about potential risks of exposure, most
of these manufactured compounds remain inade-
quately tested in relation to human safety. Through
inhalation, ingestion, dermal application, injection
or surgical implantation, vertical transmission, and
via the olfactory conduit, many individuals through-
out the world have been exposed to various toxic
metals, petrochemical byproducts, and assorted
synthetic compounds. Recent research confirms that
some chemical agents are persistent both in the
human body and in the environment and food chains.
The scientific community has begun to witness the
Emerging human and animal studies suggest sig-
nificant potential toxicity associated with exposure
to, and accrual of, some chemical compounds. As a
result, numerous scientific journals are disseminating
emerging information about the potentially adverse
impact of bioaccumulative toxicant exposure. While
public health measures have been implemented in
some areas to protect individuals from further expo-
sure, interventions to eliminate persistent toxicants
from the human body (‘detoxification’) are also being
investigated with the objective of preventing or ame-
liorating health problems in those who have accrued
University of Alberta, Edmonton, Alberta, Canada, T6G 2R3
Stephen Genuis, 2935-66 Street, Edmonton Alberta, Canada.
Human and Experimental Toxicology
ª The Author(s) 2010
Reprints and permission:
Hum Exp Toxicol OnlineFirst, published on April 16, 2010 as doi:10.1177/0960327110368417
In this paper, background knowledge with an over-
view of bioaccumulative toxicant exposure is initially
presented to highlight the issue of persistent toxicants
and to emphasize the ineluctable need for therapeutic
interventions. This is followed by the specific
objective of this work: to assess and present a review
of the available research literature examining inter-
ventions that can be used within clinical settings to
facilitate the removal of persistent bioaccumulative
toxicants. Finally, a case history is offered to
emphasize the potential clinical results achieved with
detoxification of adverse chemicals.
This review was prepared by assessing available
medical and scientific literature from Medline, as well
as by reviewing numerous books, toxicology journals,
conference proceedings, government publications,
and environmental health periodicals. Searching
techniques included key word searches with terms
related to elimination of chemical toxicants. A pri-
mary observation, however, was that limited scientific
literature is available on clinical techniques dealing
with elimination of persistent toxicants or clinical out-
comes associated with such interventions. Available
publications were reviewed and incorporation of data
was confined to information deemed to be of clinical
significance. After the research and clinical data were
compiled, information relevant for clinical practice
was prepared in discussion format as well as in table
form and is presented in this manuscript. The format
of a traditional integrated review was chosen as such
reviews play a pivotal role in scientific research and
professional practice in medical issues with limited
primary study and uncharted clinical territory.1
Overview of toxicant exposure and
Emerging evidence from several scientific and gov-
ernmental sources continue to suggest that we live
in an era of unprecedented exposure of population
groups to myriad chemical agents.2,3The Centers for
Disease Control (CDC) recently published the
findings of the ‘Fourth National Report on Human
Exposure to Environmental Chemicals’ – the largest
ever toxicant study on humans – and found that most
Americans, young and old, have bioaccumulated
numerous toxicants within their body.2An American
Red Cross study on newborn blood also confirmed
that unborn children are routinely exposed through
vertical transmission.4Emerging data from various
nations5-11verifies that routine exposure of popula-
tion groups to and/or accrual of assorted xenobiotics
(foreign chemicals) is not isolated to America but has
become a prevalent problem in many jurisdictions.
With myriad chemical compounds finding their way
into the human body, evidence has recently emerged
which suggests that exposure to, and bioaccumulation
of, some toxicants are eroding human health.12
Although some toxic chemicals are being restricted
and banned, many of today’s populations have
already been harmed by bioaccumulated toxicants.
Numerous examples in the medical and environmen-
tal literature continue to demonstrate the problem.
Elevated body burden of dioxins and related com-
pounds, for example, have been associated with high
blood pressure, elevated triglycerides, and glucose
intolerance among the Japanese population9; the
ongoing presence of lead in some paints and other
materials have inflicted significant harm upon chil-
dren in various jurisdictions including Africa and
North and South America8,13,14; arsenic in the water
supply has caused serious health issues for exposed
groups in India and Bangladesh5-7; unfolding evi-
dence suggests increased prevalence of altered hepa-
tic, immune, and thyroid function in a large
population of people exposed to drinking water con-
taminated with perfluorinated compounds in West
Virginia15; and increasing evidence is emerging about
the causal link between toxic exposure and illness in
Gulf War veterans.16In response to emerging
research linking toxicant exposure to health sequelae,
important public health initiatives to preclude further
exposure have been instituted in some areas.
Groups such as the World Health Organization, the
United Nations, various non-governmental organiza-
tions, and several national governments have (i) spon-
sored epidemiological toxicant research, (ii) devised
precautionary avoidance strategies, and (iii) instituted
educational programs for health professionals about
toxicant exposure.17Furthermore, various interna-
national governments are responding by declaring
some chemicals to be toxic, by banning certain chem-
ing into international treaties to reduce emission of
some chemical agents, with legislation that least-
health initiatives are crucial to prevent further expo-
sure, additional measures are also required. For the
generation of individuals already exposed, the prover-
bial fox has already entered the chicken coop and the
2Human and Experimental Toxicology 000(00)
pressing need for strategies to effectively eliminate
bioaccumulated toxicants in order to address and pre-
clude toxicant-related illness is evident.
In order to meaningfully discuss potential therapies
to address the problem of toxicant bioaccumulation,
an overview of some of the issues and challenges
related to toxicant exposure and diagnosis will be
initially presented. Toxicant chemical compounds
generally fall into one of five broad categories (with
some overlap): i) toxic elements; ii) petrochemicals;
iii) synthetic chemicals; iv) chemical byproducts; and
v) biological toxins. (Figure 1) It is important to note
that human metabolites of some parent chemical com-
pounds within these categories may also be active and
inherently toxic to the human organism. Elements are
chemicals often found in nature and are basic building
blocks of matter. While some elements such as cop-
per, iron, and zinc are essential for human health and
only toxic in excess, there is no known biological role
for lead, cadmium, aluminum, mercury, arsenic, and
other exclusively toxic elements for which there may
be no ‘safe’ level within the human body. Petrochem-
icals are compounds derived or extracted from raw
materials of petroleum or other hydrocarbons – they
include crude oil, diesel, and natural gas and may be
components of products such as detergents, plastics
and fertilizers. Synthetic chemicals are man-made
creations, which are manufactured from basic labora-
tory compounds in order to yield novel chemical
agents with properties that have potential industrial
or domestic application. Chemical byproducts result
from the decomposition, manufacturing, processing
or combustion of various compounds. Examples of
such byproducts include polycyclic aromatic hydro-
carbons (PAHs) formed from burning wood, coal or
tobacco; dioxins and furans produced in municipal
waste incineration or paper pulp bleaching; and
acrylamide formed in carbohydrate-rich foods such
as potatoes that are fried, baked, or roasted at high
temperatures. Biological toxins including bacterial
endotoxins and fungal mycotoxins are byproducts or
metabolites produced by living microbes such as bac-
teria or mold. While some mycotoxins such as ergot,
for example, may have practical application, many
mycotoxins are profoundly toxic to human health.18
As mentioned, there is overlap in this categorization
as some toxicant compounds, for example, may be
active metabolites of chemical byproducts formed
from the processing or combustion of synthetic com-
pounds using agents originally derived from petro-
Recognized challenges associated with
human toxicology research
With the recent claim by the CDC that ‘virtually all
human diseases result from the interaction of genetic
susceptibility and modifiable environmental fac-
tors,’19increased attention in the medical community
is being devoted to identifying modifiable environ-
mental determinants such as chemical toxicants that
may cause or trigger illness. Although widespread
recognition of the toxicant problem and its association
with human illness is increasing, precise understand-
ing of the health impact posed by the spectrum of
stockpiled xenobiotics is lacking. While extensive
study is underway to definitively delineate health
effects associated with specific toxicants, such
research is fraught with challenges.
There is limited available research in some
aspects of clinical chemistry including (i) excre-
tion pathways for many compounds, (ii) out-
comes of interaction between many toxicants
and inherent biochemistry, (iii) synergy and inter-
action between assorted xenobiotic compounds,
and (iv) toxicokinetics for many of the chemical
agents currently in our environment. As a result,
a primary problem with human toxicant research
is that bioactive mechanisms of impact for many
contemporary chemical agents are not yet well
Figure 1. Categories of potentially toxic chemicals.
Genuis S J3
tive clinical trials on the human health effects of
exposures as it is unethical to expose individuals
or groups to potentially toxic compounds –
accordingly animal studies as well as protracted
and less reliable human observational studies are
used instead. With diagnosed evidence of poten-
term observation in some situations. Despite other
types of research evidence, the lack of prospective
randomized controlled trials has resulted in skepti-
icants as a common determinant of illness.
III) Limitations of animal research: Although animal
research has been the primary pathway for toxi-
cant safety testing thus far, this type of research
has limited usefulness. Animal detoxification
mechanisms are often different than human sys-
tems,20and most animal testing explores short-
term outcome rather than chronic effects. The lag
from exposure to clinical outcome in people may
be delayed for many years or decades – short-
term animal safety research may have no validity
when applied to delayed adverse outcomes in
IV) Chemical sequestration:
research and biomonitoring is difficult as stan-
dard testing to assess levels of some accrued tox-
icants is of limited value as many chemicals
sequester in tissues and may not remain primarily
in the bloodstream or may not be excreted in
urine. Levels measured in peripheral blood or
urine on a single occasion only represent a ‘snap-
shot’ that may not reflect the actual degree of
contamination. Much research, however, has
been based on serum or urinary levels of toxi-
cants, a problem which limits the validity and
usefulness of such study. Serum levels of xeno-
biotics tend to under-represent the total body bur-
den of toxicants and serum values for some
toxicants are unreliable as levels fluctuate due
to movement in and out of cells depending on
various factors including exercise and caloric
intake.21Furthermore, tissue biopsies are not
reliable as levels of toxicant accrual may vary
from tissue to tissue and from one area of the
body to another.
V) Genomic variability and chemical interaction:
Many confounders also make it difficult to
interpret the results of toxicant outcome studies.
Each individual, for example, has a unique gen-
ome and may respond differently to toxic expo-
sures. Synergy or interaction between various
chemical compounds may also alter the impact
of any individual agent. With the array of combi-
nations and permutations of potential exposures
continuing to unfold at an unprecedented rate, the
reality is that there is a paucity of credible data on
health sequelae of bioaccumulation for each indi-
vidual compound or for collective chemical
VI) Conflict of interest: Another concern is the influ-
ence of industry on chemical research. Many
toxicology experts are employed or affiliated
with companies that produce potentially toxic
chemical products. It is repeatedly alleged that
some industries hire scientists to further their
message and to deflect attention away from the
potential adverse impact of some toxicants.22
Furthermore, some scientific publications assign
industry-affiliated reviewers to assess emerging
research on products produced by their compa-
nies, placing reviewers in a conflict-of-interest
position with the power to influence decisions
about publication of research exposing harm
from such products.
VII) Inconsistent approach: There has been discus-
sion in toxicological publications about the need
to provide standardized objective approaches to
toxicological analysis in order to optimally assist
with decisions on harm causation and to improve
subsequent decision making in risk manage-
ment.23A move towards evidence-based toxicol-
ogy (EBT) is underway, which aims to use
objective approaches in a structured manner
based on emerging scientific evidence, systema-
tic methodological analysis, and transparent
technique.24A criticism of EBT, however, is that
this movement is heavily supported by certain
industries who – rather than wishing to demon-
strate definitive evidence of safety – wish to
raise the bar of ‘proof of harm’ so high that it
will be very hard to conclusively declare poten-
tially dangerous compounds as being too risky or
too toxic to release and disseminate.
In review, there are many challenges in interpreting
exposure measures, biomarkers of body burden, and
estimation of related toxic effects. Although chal-
lenges remain when attempting to conclusively
4Human and Experimental Toxicology 000(00)
quantify the impact of chemical exposures, long-term
observational research has begun, nonetheless, to elu-
tent human exposure to and bioaccumulation of
toxicants. Public health and toxicology journals con-
tinue to divulge outcomes of such research with
increasing frequency. Exposure to, and/or accrual of,
selected chemical compounds appears to increase the
risk for potentially serious clinical sequelae including
gulation,26immune alteration,27congenital anoma-
as well as neurological and psychiatric
dysfunction.29In response to unfolding research
demonstrating considerable harm, increasing explora-
tion of interventions and strategies to facilitate elimi-
nation of bioaccumulative toxicants is underway.
Study of the endogenous physiological excretion of
toxic compounds has been the subject of many books
and papers over the last few decades.30As the field of
environmental health sciences in relation to multiple
toxicant bioaccumulation is in its relative infancy,
however, research into therapeutic interventions to
eliminate the body burden of toxicants to prevent or
overcome adverse health outcomes is, thus far, very
It is important to clarify that there is a distinction
between external exposure, internal dose, and accrued
internal bioaccumulation. While individuals may be
exposed to adverse chemical compounds, some agents
are rapidly metabolized and excreted and do not
remain in the human body. Other compounds may
remain in the human body for a period of time
depending on the efficiency of inherent detoxification
mechanisms and the chemical properties of the agent.
Finally, some compounds are poorly excreted and
tend to bioaccumulate in tissues. Internal dosing of
toxicant compounds cannot simply be determined
by blood or urine testing as each distinctive com-
pound behaves differently and some agents store in
tissues with minimal or no evidence of the adverse
compound in routine blood or urine testing.
Essentially, there are three routes to minimize
accrual of xenobiotics: (i) precautionary avoidance
of exposure; (ii) endogenous excretion; and (c) thera-
peutic interventions to enhance elimination. The main
routes of elimination are through renal excretion,
fecal elimination, and pulmonary exhalation. Other
endogenous mechanisms of excretion, however, may
include elimination through sweat, hair, nails, and
secretions such as breast milk and tears.
Excretion pathways for different compounds vary
depending on the chemical nature of the toxicant and
the facility of the endogenous biochemistry to deal
with it. In order for endogenous excretion physiology
to operate effectively, proper nutrient status required
for detoxification biochemistry is essential. Defi-
ciency of nutrient compounds involved in conjugation
and toxicant elimination, such as glutathione, glycine,
and taurine, may impair normal elimination and result
found in nuts, seeds, greens, beans, rinds, and whole
grains is also required for efficient fecal elimination
eral, compounds that remain lipophilic and their lipo-
philic metabolites tend to be excreted primarily
and their metabolites are generally eliminated in the
urine. Some bile-excreted xenobiotics that are surface
active, or which possess structural or behavioral prop-
erties similar to endogenous bile acids, however, may
The EHC is a normal physiological re-absorption
mechanism for recycling bile acids and acts as a
means to conserve required biological compounds;
this mechanism, however, can act as a hindrance to
elimination of some toxicants. After hepatic process-
ing, delivery of toxicant compounds into bile with
subsequent excretion into the intestine accounts for
much elimination. In addition, some compounds
appear to be delivered directly to the lumen of the
intestine by exfoliation of the epithelium or exudation
across the mucosa.30
released into the gastrointestinal (GI) tract as well
as conjugated toxicants freed by the action of enteric
micro-organisms, however, become available to be
re-absorbed and return to the liver through the
EHC. Consequently, the cycle of excretion and re-
absorption commences over and over again. The net
result is that the process of recycling toxicants results
in (i) repeated elimination by the liver thus consuming
energy and nutrients, (ii) it severely prolongs the half-
life of involved toxicant compounds, and (iii) it
increases the potential health risk because of retained
xenobiotics and persistent exposure.
mechanism in the kidneys. Some compounds may
Genuis S J5
bioaccumulate due to renal tubular re-absorption
mediated through organic anion transporters.32,33
Although there has been discussion on the impact of
pH changes on renal re-absorption of some toxicants,
determinants of renal excretion are not completely
Persistent compounds, depending on their chemical
nature, tend to be stored in tissues or remain in serum,
potentially affecting health outcomes. As an inherent
defense mechanism to limit exposure of vulnerable
organs to toxicants, lipophilic toxicants tend to be
sequestered and stockpile within adipose tissue found
in various organs including the brain. Some toxicant
non-lipophilic compounds, however, may stay in blood
with increased exposure to target organs and tissues. In
the plasma, serum proteins may bind chemicals in
order to limit their potential toxicity. Within the circu-
lation, such toxicants are routinely shunted to the liver
for elimination. While toxicant excretion can be
tion, or deficiency of nutrients required for hepatic pro-
cesses such as conjugation, some compounds remain
persistent in the human body because of recycling
within the EHC and/or renal tubular re-absorption.
a family of commonly used synthetic chemicals routi-
nely found in furniture, clothing, carpets, and food
packaging in order to repel oil and stains and are also
used in the manufacturing of polytetrafluoroethylene
(Teflon) – a non-stick surfacing often found in cook-
ware. Exposure to PFCs is widespread and some sub-
ochemical manufacturing plants, are highly contami-
nated. Recent research has suggested that some
common PFCs demonstrate reproductive toxicity,34
are likely human carcinogens.38PFCs remain persis-
ical stability and are extraordinarily persistent within
the human body due, in large part, to enterohepatic
half-lives in the human body – thus increasing their
potential adverse impact. Accordingly, there is
ventions to intercept the EHC to facilitate more rapid
elimination of such agents. There is no known clinical
intervention at this juncture to preclude re-absorption
of PFCs or other compounds within the kidney.
Interventions to facilitate excretion of
In order to diminish the risk associated with bioaccu-
sary to facilitate removal of such agents – this can be
achieved by endogenous processing of the chemical
into a non-toxic metabolite or by enhancing the rate
of excretion from the body. Research is underway to
find effective techniques to diminish the total body
burden of toxicants, a process sometimes referred to
as detoxification. With limited science reported in
medical journals on methods to facilitate excretion of
accumulative toxicants, the area of detoxification thus
far has gathered attention primarily among practi-
tioners of complementary and alternative medicine
(CAM). ‘Detoxification Centers’ have become more
prevalent, sometimes offering remedies with limited
orno scientific validation
‘cleanses’ and ‘detox’ treatments to treat increasing
numbers of patients who believe they have accumu-
lated toxicants as a determinant of their affliction.
Table 1 provides an overview of approaches
While some interventions that purport to facilitate
toxicant excretion such as ‘ionic foot baths’ or ‘ayur-
vedic leech therapy’ lack vigorous scientific analysis
and clinical trial evidence, there has been some
research reported in the scientific literature about
selected interventions to diminish the body burden
of toxicants. For example, with the recognition that
perspiration acts a means to excrete xenobiotics, some
reports suggest that induced sweating may be useful
in diminishing toxicant bioaccumulation. There is
limited study thus far on which specific agents are
excreted in sweat and at what rate, but research con-
firms toxic compounds such as methadone,57,69
phine,71and some heavy metals72appear in analytical
studies on sweat. Although further study is required to
determine the clinical usefulness of induced depura-
tion through thermal techniques, several studies thus
far have confirmed that induced perspiration through
sauna therapy can diminish the body burden of
assorted bioaccumulated toxicants including persis-
tent polychlorinated biphenyls (PCBs), polybromi-
hexachlorobenzene, and various other toxicants in
Another recognized intervention to diminish the
body burden of some bioaccumulated toxicants is the
6Human and Experimental Toxicology 000(00)
Table 1. Selected interventions purported to facilitate detoxification of toxic materials
Type of interventionAlleged mechanism of actionEffectiveness
Fasting Lipolysis of fat cells releasing stored xenobio-
tics into circulation and available for excretion
Caloric restriction confirmed to significantly
increased serum concentration of some
Consistent confirmation of enhanced excre-
tion of stored toxicants not found in the sci-
Recognized treatment for some types of heavy
metal poisoning.40,41No evidence in the liter-
ature for removal of other types of toxicants
Evidence in the scientific literature for excre-
tion of some protein-bound toxicants42,43
Massage Mobilization of toxins sequestered within
muscle tissue into the circulation and available
Use ofagents known to chemically bind specific
toxins and to allow for excretion of chelate-
Removal of a portion of the plasma compart-
ment of blood – which contains protein-bound
Sends a current into the body to generate
positively charged ions that allegedly attach to
negatively charged toxins and discards bound
toxicants through foot pores
Removes encrusted material from the colon
thus diminishing absorption of toxicants and
allowing for improved excretion of accumu-
Various mechanisms proposed including (i)
lipolysis of stored toxins in fat cells with
excretion through lungs and perspiration (ii)
enhanced enzymes in detoxification
Medications which bind to specific compounds
released into bile, preventing re-absorption
within the enterohepatic recirculation (EHC)
Technique of circulating blood through filters
outside the body to remove toxic materials
Ionic Foot Baths Consistent confirmation of enhanced excre-
tion of stored toxicants not found in the sci-
Colonic CleansingSome discussion44,45but consistent confirma-
tion of enhanced excretion of stored toxicants
not found in the scientific literature
Preliminary research confirms enhanced
excretion of some compounds with
Bile Acid Sequestrants Numerous studies confirm binding and release
of specific compounds by some bile-acid
Effective with low molecular weight com-
pounds. Limited ability to remove macromo-
lecules such as protein-bound toxins.51
Research to improve this technique is
Emerging evidence of the role of prebiotics and
probiotics in excretion of some toxicants53-55
Restoration of damaged germ environment in
the intestinal flora facilitates GI removal of
Induced perspiration with excretion of toxi-
cants into sweat
Dietary interventions that allegedly stimulate
endogenous release of stored toxicants
Sauna therapy Numerous studies have confirmed release of
Consistent confirmation of enhanced excre-
tion of stored toxicants not found in the sci-
Evidence for removal of excess compounds in
specific conditions such as iron overload
Confirmation of enhanced excretion of stored
toxicants not found in the scientific literature
Evidence for detoxifying effectiveness of
selected supplements,59,60but confirmation of
enhanced excretion of the spectrum of stored
toxicants by myriad supplements is not found
in the scientific literature
Cleanses through vari-
ous food and drink
PhlebotomyRemoval of toxicants retained in red cells and
Leeching Leeches allegedly suck toxins from the blood
Herbal Supplements Some supplements noted to facilitate excre-
tion by enhancing intrinsic detoxification
Genuis S J7
use of medications that bind and remove certain
heavy metals including lead and mercury.40,41Chem-
ical therapies such as dimercaptosuccinic acid
(DMSA) and dimercaptopropane sulfonate (DMPS),
for example, have been found to be safe and effective
chelators of some heavy metals.81-84Chelating agents
work, in part, by interference with renal re-absorption
of some heavy metal toxicants. The contention that
chelation therapy has the ability to detoxify and
cleanse the body via binding and removing all toxi-
cants (including assorted synthetic chemical com-
pounds) in the blood or tissues, however, is not
supported by evidence in the literature.
In addition to single interventions, some methods
of detoxification can be combined to facilitate xeno-
biotic removal. Hemodialysis in combination with use
of chelating agents, for example, may be a safe and
effective means to rapidly lower toxic metals – a
potentially important strategy as high levels of
mercury and lead can impair renal function, and con-
centrated exposure to cadmium can be toxic to the
With the recognition that caloric restriction appears
to greatly enhance lipolysis with release of assorted
toxicants,38fasting techniques and restrictive dietary
measures have also been explored as a means to dimin-
ish the body burden of toxic compounds.39Concern
has been expressed about severe caloric restriction,
however, as it may result in a surge of toxicants enter-
ing the blood stream and the cerebral circulation,21,39
potentially precipitating health compromise in some
patients. In addition, vigorous exercise also appears
excretion of various toxicants.47,48
Certain nutrient interventions are also being
pounds87– malic acid, for example, appears to assist
with the removal of retained aluminium,59,88while
emerged in recent literature which focus on interven-
tions to facilitate elimination of persistent compounds
such as PFCs by interrupting enterohepatic recycling.
Therapies to circumvent the enterohepatic
Although most synthetic chemical compounds appear
to be readily excreted in healthy individuals who are
no longer exposed, some compounds persist as they
are not easily metabolized or as a result of recycling
within the EHC. Interventions to circumvent re-
absorption within the EHC offer promise to diminish
the body burden of persistent toxicants by facilitating
excretion – with potential benefits for human health.
With variations in chemical behavior and structure
between different chemical agents, however, dissimi-
lar interventions may be required to facilitate binding
of dissimilar compounds in order to achieve EHC
interruption – that is no one chemical therapeutic
intervention is likely to circumvent enterohepatic
recycling for all toxicant compounds.
Four types of pharmaco-therapeutic interventions
have been discussed in the literature as potentially
useful in circumventing the EHC. First, therapies that
preclude fat absorption have been found to enhance
the excretion of fecal fat and lipophilic toxicants –
to this end, research is underway on non-absorbable
Table 1 (continued)
Type of interventionAlleged mechanism of action Effectiveness
Medicated baths and
Immersion of body into medicated bath or hot
springs facilitates absorption of compounds
that enhance endogenous release; or alterna-
tively, ‘magnetic’ effect to draw out toxins into
Medicaments or foodstuffs inserted per rec-
tum into the colon designed to stimulate liver
dumping of toxicants into bile and gall bladder
release into the intestine
Through cation exchange, ingested zeolites
release beneficial elements while capturing and
binding toxicants. Heavy metals and other
toxins are allegedly absorbed into the zeolite
cage and then excreted
Confirmation of enhanced excretion of stored
toxicants not found in the scientific literature.
Theoretical benefit of absorption of sulfur
(involved in some detoxification biochemistry)
in natural hot springs
Some discussion44in the scientific literature
but consistent confirmation of enhanced
excretion of stored toxicants not found
Liver and gall bladder
Zeolites (from naturally
occurring volcanic sedi-
Animal research suggests safety61,62and potent
effect with mycotoxins.63,64Binding of some
toxicants65and heavy metals66-68in water, soil,
and other mediums. Human research not
found in scientific literature
8Human and Experimental Toxicology 000(00)
fats that act as a lipophilic sink.89Preliminary results
confirm that these types of compounds, such as
Sucrose Polyester (Olestra), have been effective in
enhancing fecal elimination of a variety of chemical
agents including dioxins, furans, PCBs, and hexa-
chlorobenzene.89,90Other compounds such as mineral
oil91also appear to have some success in enhancing
excretion by this mechanism.
Secondly, there has been preliminary work on
interruption of fat absorption by interfering with pan-
creatic lipase. The drug Orlistat (Xenical) is a pan-
creatic lipase inhibitor that interferes with digestion
of triglyceride and thereby reduces absorption of diet-
ary fat.92Animal work suggests that enhanced excre-
tionof some lipophilic
hexachlorobenzene may be facilitated by use of these
types of agents.31
pounds that accumulate toxic agents from within the
GI tract. For example, activated carbon such as char-
coal and other compounds including bentonites, cer-
tain clays, and zeolites appear to have adsorbent
action, which may decrease re-uptake of some
compounds into the body. (Some zeolites appear to
also work through cation exchange mechanisms.)
Although animal studies have demonstrated promise,
insufficient human research work has been done thus
far to conclusively determine the clinical value of
adsorbent compounds for toxicant removal. Some
adsorbents, for example, appear to be effective in
removing selected biological chemicals such as afla-
toxins in animals.93,94Activated charcoal, however,
has demonstrated inconsistent efficacy with elimina-
study is required to assess the usefulness of these
agents with the range of bioaccumulative compounds.
The fourth mechanism to circumvent enterohepatic
well known and studied of these is cholestyramine
(CSM). CSM is a strongly basic non-absorbable resin
that effectively binds various agents through anion
exchange, interrupts enterohepatic recycling, and pre-
vents intestinal re-absorption. As well as effectiveness
have been shown to bind various bacterial endotox-
some external biotoxins,103drugs such as methotrex-
ate,49and they have also been used as agents to lower
cholesterol levels.Cholesterol, forexample, entersthe
intestine as a component of bile and is absorbed again
tion and re-absorption recur – CSM binds cholesterol,
prevents enterohepatic recycling, and lowers serum
cholesterol by facilitating excretion.
A paper published in the New England Journal of
Medicine reported on a controlled clinical trial where
CSM was successfully used to diminish serum levels
of a toxic pesticide in exposed people50– a significant
increase in the fecal elimination as well as decrease in
body burden was observed in the CSM-treated group
compared to the control group. Other non-absorbable
resins such as colestimide have also been effective at
eliminating certain toxicants, including PCBs.49,104In
order to preclude potential adverse sequelae of these
pharmaceutical compounds, particularly in develop-
ing children (such as induced deficiency of fat-
soluble micronutrients by binding and eliminating
these nutrients), research continues on the use of her-
bal agents such as saponins compounds (originating
from soy or the yucca plant) which are alleged to have
a similar BAS mechanism of action and which purport
to be associated with less adverse effects.105,106The
author was unable to find ample study in the scientific
literature to determine the validity of this proposed
hypothesis about saponins.
Plasmapheresis is a blood purification process that
involves removal of whole blood from the body,
separation of whole blood into the plasma component
and red cellular elements, and reinfusion of the cells
back into the body suspended in a plasma substitute
such as saline, donor plasma, or donor albumin. The
end result of therapeutic plasmapheresis, otherwise
referred to in literature as therapeutic plasma
of the body’s own plasma without depleting red blood
cells, and with the potential to remove protein-bound
toxic substances contained within the plasma.
Although therapeutic plasmapheresis has been
used in selected cases of autoimmune, infectious,
rheumatic, and other types of disease states, this tech-
nique has recently been incorporated as a method of
clinical detoxification. As well as successful out-
comes in the treatment of potentially fatal mushroom
poisoning,109plasmapheresis has been effectively
employed to remove some pharmaceuticals, espe-
cially those with a high protein-binding capacity (thus
not amenable to dialysis), from the circulation. For
Genuis S J9
blockers such as diltiazem111and verapamil,112hor-
monal agents including L-thyroxine,113phenproba-
mate,42and rituximab.43Removal of protein-bound
heavy metals, such as mercury,114,115vanadium,116
and chromium117and elimination of pesticides such
as paraquat118,119and organophosphates120has also
been accomplished through plasmapheresis. Increas-
ing study is underway to determine the range of tox-
Although scientific study is underway to develop
efficacious testing and treatment to eliminate the
spectrum of adverse chemical agents, the prospect
of widespread clinical application of such diagnostic
and therapeutic measures remains low when consider-
ing the lethargic continuum of knowledge translation
in medical practice.121,122With the ubiquitous prob-
lem of toxicant bioaccumulation and the link to ill-
ness, however, it is suggested that clinicians become
increasingly apprised of the need for such testing and
therapy. A case history is presented to illustrate the
potential outcome with elimination of toxicants.
Case history as an example of chemical
In March of 1996, a generally healthy 33-year-old
single woman in apparently excellent physical condi-
tion – non-smoker, non-alcoholic, never used illegal
drugs, no prior history of mental or physical illness
– suffered what was subsequently diagnosed as an
acute, full-blown manic episode. Symptoms included
visual hallucinations, insomnia, cognitive impair-
ment, and delusional thoughts where the individual
claimed to be receiving direct messages from the
spirit world and from God. Her family brought her
to the University Hospital of a major center as they
were concerned with the sudden change in behavior.
As the patient had been employed in a printing
company for 15 years and was exposed to numerous
chemical toxins through direct skin contact and inha-
lation in poorly ventilated conditions, the family
asked the treating physicians to assess for chemical
poisoning. They claim the physicians appeared to
ignore this information and immediately diagnosed
her as having manic-depressive illness with psychotic
features. She was promptly admitted to a psychiatric
unit and antipsychotic medication was commenced.
For a period of more than 2 years, she remained
very ill and was given various medications from
which she suffered numerous harsh side effects
including involuntary movements and a weight gain
of 80 lbs. Despite pharmaceutical management, she
continued to have manic episodes and required recur-
rent psychiatric hospitalization. She and her family
were informed that her mental disability was an incur-
able chronic condition that she had to learn to live
with. Upon considering her alleged prognosis, the
patient became increasingly suicidal.
In 1998, the individual was seen by a physician
trained in environmental health sciences and she
underwent various investigations confirming she had
bioaccumulated high levels of lead. As well as avoid-
ance of further toxicant exposure, chemical detoxifi-
cation of lead was undertaken with a heavy metal
chelator and values of lead progressively diminished.
Concomitant with the decline in accumulated lead,
her psychiatric symptoms gradually subsided and all
medication was discontinued. The individual has
remained generally well for over 10 years, with no
evidence of either bipolar disease or sustained
recurrence of symptoms or signs of mental illness.
The weight issue has persisted, however, as has
intermittent difficulty with insomnia. After recovery,
she was told by several doctors that detoxification
treatment was nothing more than ‘placebo.’ Other
accounts in the medical literature also document
mental health affliction in association with toxicant
exposure,29,123-125with recovery in some cases
following measures to avoid or detoxify adverse
We live in the age of ubiquitous chemical toxicity.
There is increasing global attention to the problem
of persistent pollutants, both in the environment and
within the human body. Compelling research suggests
that accrued toxicants may lead to increased health
risks in the long term. With the 21st century reality
of escalating toxicant exposure and bioaccumulation
among individuals and population groups, research
is now underway to find potential interventions to
facilitate excretion of persistent toxicants in order to
diminish the body burden and to preclude or over-
come related health problems.
Study of interventions to remove bioaccumulated
toxicants, however, remains in its relative infancy and
much scientific research needs to be done to identify
credible modalities with potential to eliminate
accrued xenobiotics. With the scientific knowledge
10 Human and Experimental Toxicology 000(00)
currently available, how should clinicians and the
public health community address the problem of tox-
Thus far, three phases of intervention are required
to address the problem of toxicant bioaccumulation.
First, it is evident that precautionary avoidance to pre-
clude further toxicant exposure is crucial.126This can
be achieved by educational endeavors in schools and
through media to promote awareness among individ-
uals and population groups. This objective also
requires regulation and public legislation to preclude
the release of harmful chemicals into environments
where individuals may be exposed. With considerable
lag time between development of chemical com-
pounds and the extended process required to con-
firm safety of each compound, it behooves the
public health community and government officials
to consider whether ‘proof of safety’ rather than
‘proof of harm’ should be required before potentially
health-compromising compounds continue to be
unleashed into the environment.127
Secondly, proper functioning of inherent toxicant
elimination mechanisms need to be maintained in
exposed individuals. Investigation and treatment for
any physiological impairment of excretion should be
undertaken to secure maximal liver, kidney, and pul-
biochemicals involved in excretion and detoxification
physiology, such as reduced glutathione, need to be
securedin orderto maintain optimal and intact toxicant
Finally, with much discussion in the popular media
and alternative medicine circles about ‘cleansing’ and
‘detoxing,’ it is hard to winnow fact from fable in the
area of detoxification therapies. In order to determine
potential efficacy in the clinical care of exposed
patients, therapeutic interventions to enhance elimi-
nation of persistent compounds require carefully
designed clinical trials to determine evidence-based
scientific validity for each modality. As the field of
environmental health sciences is an emerging clinical
area of medical practice with enormous public health
significance,128it is imperative that the scientific and
medical community stay apprised of the expanding
problem of persistent toxicant bioaccumulation and
become familiar with evidence-based clinical inter-
ventions that facilitate the removal of adverse chemi-
Declaration of conflict of interest
There are no conflicts of interest.
No funds have been received for any part of this work.
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