Until recently there was great interest in the potential role of
Chlamydia pneumoniae (CP)
as a cause of
atherosclerosis, ischemic heart disease and stroke. Negative results
from clinical trials using antibiotic therapy led to subsequent loss of
interest in this theory, notwithstanding a very large amount of
excellent scientific and epidemiologic data that supports continued
Chlamydia pneumoniae is the principal suspect for infectious causation
of cardiovascular disease. Clinical trials with antibiotic therapy were
based on the mistaken assumption that an active infection with CP was
needed. We now know that CP can persist intracellularly in a cryptic and
arrested state, that cannot be cultured, is immunologically muted, and
becomes resistant to antibiotics. Moreover, treatment with
antibiotics can cause CP to convert into this inert, resistant, and
hidden state. Failure of antibiotic treatment is therefore expected
and can easily be explained by the complex and multiphasic growth cycle
of CP. Consideration of CP as a cause of atherosclerosis remains an
important avenue for research.
Atherosclerosis is Successfully Treated with EDTA Chelation Therapy
n a different, but related field, intravenous EDTA chelation therapy was
recently shown to be of marked benefit in atherosclerotic heart disease,
which suggests a new approach to CP research. The mechanism of action by
EDTA chelation as a treatment for . atherosclerosis remains unknown,
despite a number of theories. It is theorized in this paper that benefit
from EDTA results from an action against CP.
CP as a cause of atherosclerosis can at least partially be explained by metallo-proteins
that are created or upregulated by CP. The principal effect of the EDTA
is binding of metals. It is estimated that from one third to half of all
proteins in the body require a metal co-factor for
biological function. EDTA can disassociate metals from those proteins.
Possible evidence that this occurs comes from early (although anecdotal)
reports of success using intravenous EDTA to treat rattlesnake and spider
bites. Those toxic venoms contain a variety of metallo-proteins that mediate
A $30 million, NIH funded clinical trial of intravenous EDTA chelation
therapy has shown success in treatment of atherosclerotic cardiovascular
[5,6] In that "Trial to Assess Chelation Therapy (TACT)," the
composite primary endpoint was death, reinfarction, stroke, coronary
revascularization, or hospitalization for angina. A total of 1,708
post-myocardial infarction patients who were 50 years or older received
55,222 infusions of either disodium EDTA or placebo, with a median follow-up
of 55 months. Overall, EDTA chelation therapy reduced cardiovascular events
by 18%, with a 5-year number needed to treat (NNT) of 18. A subgroup of 550
patients with diabetes mellitus experienced a 41% reduction
in the primary
endpoint (5-year NNT = 6.5), and a 43% 5-year relative risk reduction in
all-cause mortality (5-year NNT = 12).
Doubtful that Removal of Xenobiotic Metals is the EDTA Mechanism
EDTA has one principal action in the body—it binds (chelates) polyvalent
cationic metals. The currently favored explanation for benefit in
atherosclerosis is by removal of xenobiotic metallic toxins (toxic heavy
metals). However, the link between xenobiotic metals and atherosclerosis is
weak. Consider also that provoked excretion of toxic metals following
chelation is no greater in healthy control subjects, when compared with patients
suffering atherosclerotic cardiovascular disease. [author's unpublished
data] EDTA binds to essential, nutritional metals with a much stronger
affinity, greater by an order of magnitude compared with known toxins.
It is a common misconception that toxins remain toxic in a linear fashion
down to low levels—the "linear-no-threshold model." This is rarely true.
Threshold levels for safe tolerance exist for virtually all toxins, below
which they are safely tolerated. Conversely, excessive levels of essential
nutritional metals all cause toxicity. Provoked urinary increase of a range
of metals occurs following infusion of EDTA. Increases of essential
nutritional metals greatly exceed excretion of known toxins.
All metals are potentially toxic, even essential nutrients. That applies to
all metals, without exception, not just known toxins. Essential nutritional
metals also become toxic when maldistributed within the body (i.e.,
intracellular calcium or sodium). There commonly exists a narrow margin
between optimal and toxic levels for metals. A two or three fold increase
can be toxic.
The Table below is taken from data published in the TEXTBOOK ON EDTA
CHELATION THERAPY,  showing that EDTA chelation has a much greater impact
on a number of essential nutritional metals, compared with known
toxins.. These data suggest that chelation of essential nutritional
elements might be more important for benefit from EDTA than action on
toxic, xenobiotic metals.
This author personally chelated many hundreds of patients with EDTA between
1972 and 2003. Utilizing state-of-the-art inductively coupled argon plasma
photo-emission spectrometry and atomic absorption spectrophotometry,
provoked urinary increases of a range of metals were measured before and
after infusion of EDTA in a large series of sequential patients.
Approximately one-third of tested chelation patients were healthy, with no
known evidence of atherosclerosis. They elected chelation for purely
preventive reasons . They were often spouses, who would otherwise have
needed to wait idly for several hours while a family member received
treatment. Others were healthy individuals, convinced that chelation therapy
would delay or prevent atherosclerosis in later life.
Results of those tests are published in the
TEXTBOOK OF EDTA CHELATION
, chapters 37 and 37.  and are partially summarized in the table
above. In particular, excretion of toxic elements was essentially the same
for healthy individuals and compared with patients diagnosed with
atherosclerosis. No association was found to indicate a
causative relationship between toxic metals and atherosclerosis.
[unpublished data, no longer available]
Life in the 20th century causes toxic metals to accumulate in all
individuals, but usually at levels below a threshold for toxicity. These
facts argue against the theory that benefit from EDTA chelation in
cardiovascular disease results from removal of xenobiotic metals.
Chlamydia as a Cause of Cardiovascular Disease
Many published studies have linked CP to atherosclerosis.[1-4] A literature
search brings up a very large number of such studies. The data are
inconsistent and some studies fail to confirm the association. The
contradictions become understandable with newer discoveries concerning
growth stages of CP.
90% or more of the adult population eventually become infected with CP. The
incidence of infection Increases with age, parallel to the age-related
incidence of atherosclerosis. Evidence exists that CP remains in the body
for decades, perhaps throughout life, in a low-grade inflammatory but
partially dormant state, much like Varicella virus.
Although classified as a bacterium, CP has many characteristics of a virus.
It is an obligate, aerobic, intracellular, gram negative organism with a
unique growth cycle of multiple stages. Like a virus, CP hijacks the energy
metabolism of host cells for survival and replication. Unlike a virus, CP is
partially susceptible to treatment with antibiotics—but not during some stages
of its growth cycle.
The initial acute phase of CP infection commonly lasts only a week or two,
and is mainly respiratory. It can be relatively mild or even unsuspected,
following which the organism migrates throughout the body in monocytes
(macrophages). It then hibernates, as inert, cryptic, and immunologically
attenuated intracellular inclusions. These inclusions are persistent and
remain potentially infective if reactivated. They hide away for decades,
possibly a lifetime, as chronic, low-grade, lingering infections.
Traditional risk factors for atherosclerosis may trigger reactivation.
Atherosclerosis develops slowly, perhaps as a host responses to sustained
The assertions here are simplified and speculative at times. The study of CP
is complex and only partially understood.. Because virtually everyone can
harbor CP, with or without atherosclerosis, research into the presence or
absence of CP has been of little help to prove causation.
EDTA Chelation Has Anti-Chlamydia Properties
The slow, chronic, long-term, multiphasic, and variable nature of
intravascular CP prevents use of Koch's postulates, despite the
infectious nature of this disease. Traits of CP leading to atherosclerosis
require the presence of metal co-factors, that can be bound and inactivated
Significant correlations are known between metallic trace element levels in
plasma, serum, and tissues, with the occurrence and treatment of a variety
of infectious diseases. These data exist for metals that are bound tightly
by EDTA, including copper, iron, zinc chromium, and manganese.
It is counter-intuitive, but a fact, that the inside diameter of a sclerotic
blood vessel need only be increased by 10% to double the flow of blood.
Poiseuille's Law of hemodynamics (a fourth power equation) tells us that
with perfect laminar blood flow, a mere 19 percent increase in the diameter
of an artery doubles the rate of flow. In a vessel with turbulent flow
around a plaque, doubling of flow can result from less than 10% increase in
vessel diameter. In an area with compromised circulation, an increase in
blood flow of less than that could bring functional improvement and relief
of symptoms. Changes in diameter of such small magnitude cannot be detected
on arteriograms. CP might mediate such alterations in several ways, and
reduce risk of acute events. Merely smoothing over the disrupted surface of a
plaque, converting turbulent flow to laminar flow could have an important
effect. Anti-Chlamydia properties of EDTA could reduce plaque turbulence and
size, and stabilize plaque against disruption.
CP most often enters the body through the lungs. Smoking inhibits lung
defenses increasing risk of CP. Perhaps that is a reason why smoking is a
risk factor for atherosclerosis.
EDTA removes calcium from plaque, which might make CP inclusions more
vulnerable to host defenses, in addition to increasing lumen diameter.
CP needs iron for survival. Atherosclerosis is associated with increased
iron levels. EDTA strongly chelates iron. The Chlamydia growth cycle can
be disrupted by iron chelation, using deferoxamine, an iron chelator.
 EDTA is also a strong iron chelator.
Raulston JE. Response of Chlamydia trachomatis Serovar E to Iron Restriction
In Vitro and Evidence for Iron-Regulated Chlamydial Proteins. Infection and
Immunity, Nov. 1997, p. 4539–4547
EDTA chelation therapy requires many slow, infusions, lasting
hours, with 30 or more infusions, requiring several months to
achieve good benefit. Full improvement takes several more months following the
last infusion. Any proposed mechanism of action must take this delay into
consideration. If effects of CP are reduced, full healing of infected
tissues could require such time.
Although EDTA remains mostly extracellular, a powerful
extracellular-to-intracellular diffusion gradient is created during the
infusion. The fibro-calcific-lipoid nature of plaque is unlike a viable cell
and may be more permeable to the effect on of EDTA.
Bits and pieces to Think About
CP is speculated to initiate inflammatory scarring of artery walls,
which could evolve into plaque. CP induces macrophages to become the type of
foam cells associated with plaque formation. CP causes lipid accumulations
as found in plaque. CP is lipophilic. CP oxidizes LDL cholesterol. CP
releases a variety of metallo-proteins that can disrupt tissues. CP may
facilitate plaque rupture. CP releases inflammatory “shock proteins” and a
cytokine cascade that can disrupt host tissues. CP is believed by some
investigators to trigger a coagulation cascade, causing local
hypercoagulability and thrombosis. CP growth cycles have been reported to be
inhibited by statin drugs, unrelated to cholesterol. CP upregulates
production of metallo-proteinases in atheromas increasing risk of plaque
rupture. CP disrupts apoptosis of smooth muscle cells in vascular walls. CP
has been reported to cause thinning of fibrous caps on plaque facilitating
rupture. CP can cause tissue calcification and fibrosis as found in plaques.
It is further speculated that Chlamydia-specific bacteriophage activity
might genetically alter the host expression of this organism.
Chlamydia Research is Needed Relative To Effects of EDTA
It is hoped that microbiologists will find a way to investigate this theory further.
Isolated Amazon Tsimane Tribe has
Virtually No Atherosclerosis, and No Exposure to Chlamydia
this more evidence? Read more at this link.
Miscellaneous Background Information
CP has been implicated in many other chronic or autoimmune diseases, which
could explain why so many different conditions have been reported
anecdotally to improve following EDTA chelation therapy.  A slide
presentation by Dr. Charles Stratton at Vanderbilt University, is linked
below. . He reviews the complex, multiphasic CP growth cycle
and various clinical characteristics. A final linked reference
describes the complexities and medical politics encountered in a clinical
trial related to CP. 
1. Campbell LA, Rosenfeld ME. Persistent C. pneumoniae infection in
atherosclerotic lesions: rethinking the clinical trials. Front Cell Infect
Microbiol. 2014 Mar 21;4:34 [Link to Full Text
2. Fong IW. New Perspectives of Infections in Cardiovascular Disease. Curr
Cardiol Rev. 2009 May; 5(2): 87–104 [Link to Full Text].
3. Honarmand H. Atherosclerosis Induced by Chlamydophila pneumoniae: A
Controversial Theory. Interdiscip Perspect Infect Dis. 2013; 941392.
Published online 2013 Jul 17 [Link to Full text]
4. Hogan RJ, Mathews SA, Mukhopadhyay S, Summersgill JT, Timms P. Chlamydial
persistence: beyond the biphasic paradigm. Infection and Immunity.
2004;72(4):1843–1855. [Link to Full Text]
5. Lamas GA1, Boineau R2, Goertz C3. et al. EDTA chelation therapy alone and
in combination with oral high-dose multivitamins and minerals for coronary
disease: The factorial group results of the Trial to Assess Chelation
Therapy. Am Heart J. 2014 Jul;168(1):37-44 [Link to Full Text ].
6 . Gervasio A. Lamas, MD. The Road to TACT2: Updates from the Second Trial
to Assess Chelation Therapy. CardioSource WorldNews. December 2014. [Link to
7. Cranton E M (ed): A Textbook on EDTA Chelation Therapy, Second Edition,
Charlottesville, VA, Hampton Roads Publishing Co, 2001, Foreword by Linus
Pauling, PhD. Chapters 36-37
.Carver PL. Interrelations between Essential Metal Ions and Human
Diseases. Metal Ions and Infectious Diseases. An Overview from the Clinic.
Metal Ions in Life Sciences Volume 13, 2013, pp 1-28
9. Raulston JE. Response of Chlamydia trachomatis Serovar E to Iron
Restriction In Vitro and Evidence for Iron-Regulated Chlamydial Proteins.
Infection and Immunity, Nov. 1997, p. 4539–4547 [Link to Full Text]
10. Cabbage S, Ieronimakis N, Preusch M, Lee A, Ricks J, Janebodin K, Hays
A, Wijelath ES, Reyes M, Campbell LA, Rosenfeld ME. Chlamydia pneumoniae
infection of lungs and macrophages indirectly stimulates the phenotypic
conversion of smooth muscle cells and mesenchymal stem cells: potential
roles in vascular calcification and fibrosis. Pathog Dis. 2014
11. Stratton CW. Association of Chlamydia pneumoniae with Chronic Human
Diseases. Antimicrobics and Infectious Diseases Newsletter 18(7) 2000.
Elsevier Science Inc [Link to Full Text]
12. Chlamydia Slide Presentation by Dr. Charles Stratton on Chlamydia [Link
to Full Text]
13. Kepner J. Chlamydia Pneumoniae in Chronic Fatigue Syndrome and
Fibromyalgia - An Opinion, by a Patient Advocate [Link to Full Text]