Recent attempts to increase vitamin D supplementation to prevent
and treat chronic disease have arisen primarily out of observations
of low vitamin D levels (25-D) being associated with a variety of
diseases. However, new research indicates that these low vitamin
D levels are often the result rather than the cause of the disease
process, just as in the autoimmune disease, sarcoidosis. Trevor
Marshall, PhD, recently summarized this alternative perspective
on vitamin D, in a session he co-chaired at the 6th International
Congress on Autoimmunity. He and his colleagues presented in silico*
and clinical data from the last eight years, indicating that intraphagocytic
bacteria are able to block the vitamin D receptor (VDR), and this
leads to abnormally low measured vitamin D levels. A second consequence
of the bacteria-induced VDR blockage is inhibition of innate immunity.
By blocking the VDR, bacteria are able to cause persistent infection
and inflammation and thus cause many chronic diseases. Short-term
symptom reduction observed from vitamin D supplementation appears
to be due to immune suppression by precursor forms of vitamin D
that add to the bacterial blockage of the VDR. In silico data also
indicates that high levels of vitamin D metabolites suppress antimicrobial
peptide production by binding to other nuclear receptors (e.g.,
thyroid-alpha-1, glucocorticoid). Increasingly, epidemiological,
geographical and clinical data are lending support to this model
of disease. Studies using more advanced cell culture and molecular
techniques are confirming the presence of previously undetected
bacteria, including biofilm and cell wall deficient bacteria, as
well as "persisters." A greater understanding of how
bacteria resist standard antibiotic approaches is also being gained.
A protocol has been developed that is successfully restoring VDR
and innate immune function with a VDR agonist and eliminating pathogens
with low-dose, pulsed combinations of antibiotics. Immunopathological
reactions (a.k.a., Jarisch-Herxheimer reactions) occur due to increased
pro-inflammatory cytokines resulting from bacterial killing. The
result is an exacerbation of symptoms with each dose of antibiotic,
but improvement occurs over the long-term. Remission is being achieved
in numerous chronic conditions, including many autoimmune diseases
and fibromyalgia, as well as many diseases of aging. Although vitamin
D ingestion is avoided as part of this protocol, the evidence indicates
that the net result of the protocol is improved vitamin D receptor
* in silico = performed via computer simulation
Vitamin D is a topic of increasing interest and has been implicated
in many physiological processes beyond its initially recognized
role in calcium absorption and metabolism.1 Vitamin D is found in
supplements and a few foods (e.g., fish, liver, egg yolk, fortified
products). The majority of vitamin D is produced in the skin when
exposed to UV radiation from sunlight. But some have begun advocating
consumption of levels of vitamin D above the RDA, and some advocate
very high levels, ranging from 1,000 to 5,000 IU or more daily.2
Vitamin D is a secosteroid, with a close resemblance in structure
to immunosuppressive steroids. Levels of the various vitamin D metabolites
are the result of complex feedback mechanisms involving multiple
enzymes and receptors, indicating that it is regulated more like
a steroid than a nutrient.1
Short-term symptom reduction has sometimes been observed through
increases in sun exposure 3,4 or vitamin D supplementation.5 However,
this appears to be due to the anti-inflammatory effect arising from
immune suppression, analogous to the effect of a steroid, such as
prednisone. If one were to assume that the inflammation is purely
pathological, this might be considered beneficial, but evidence
that has been accumulating over many decades indicates that inflammation
in most chronic diseases is occurring in response to undetected
chronic bacterial infection (see below). Since immune suppression
can promote the increase of pathogens, the effect of vitamin D supplementation
is not likely to be harmless in this situation, but appears to have
long-term effects associated with increased levels of bacterial
pathogens. The role of this microbiota in producing the inflammation
and oxidative stress observed in so many diseases will be discussed
near the end of this article.6-8
Vitamin D from food or sun is first converted to 25-D (25-hydroxyvitamin-D)
and then converted in a second step to the active 1,25D form (1,25-dihydroxyvitamin-D)
that is able to activate the vitamin D receptor (VDR). The type
of vitamin D usually measured in the blood is the precursor form,
25-D, rather than 1,25-D, the form that activates the receptor.
Activation of the vitamin D receptor is extremely important, as
it has numerous effects, including effects on the immune system1
and cancer.9,10 However, recent research indicates that increasing
vitamin D via supplementation or sun exposure is not the way to
achieve more VDR activation in chronic disease, due to blockage
of the VDR by bacterial products.6 This insight has been put to
use in a new model of chronic disease and a new protocol.6,8,11-14
A New Perspective
on Vitamin D and a New Treatment Approach
Trevor Marshall, PhD, (Murdoch University, Australia) has developed
a model of chronic autoimmune and inflammatory diseases in which
intraphagocytic bacteria cause disease by producing a substance
that binds to and blocks the VDR.1 One such substance has been already
identified providing proof of principle.1 The VDR is important for
adequate innate immune function, including the production of numerous
antimicrobial peptides.15 These include cathelicidin and beta-defensin,
two of the body's own arsenal of internally produced antibiotics.
Thus, VDR blockage would seem to be an excellent bacterial strategy,
as it would lead to poor innate immune system function and further
growth of bacteria and other pathogens. A functioning VDR also appears
to be important in controlling cell growth and metastasis, so as
to help prevent and control cancerous growths.9,10
A protocol based on this model of disease has been achieving a high
rate of improvement/remissions in a wide array of conditions.6,11-14,16-18 It involves the use of a VDR agonist, olmesartan, which
is able to activate the VDR effectively and safely. In addition,
low dosages of combinations of select pulsed antibiotics are used
to eliminate the bacteria, which also helps restore VDR functioning.
The protocol also involves avoidance of vitamin D supplementation.
When faced with VDR dysfunction, the evidence indicates that attempting
to increase 25-D only adds to the dysregulation of the vitamin D
metabolites without being able to adequately overcome the bacteria-induced
Too much vitamin D can be harmful in two ways, according to Marshall's
work.1,6 In silico data from highly sophisticated molecular modeling
shows that high vitamin D levels can block the VDR and thus block
innate immune function.18 In addition, high levels of various vitamin
D metabolites can affect thyroid-alpha-1, glucorticoid, and androgen
receptors and disrupt hormonal control and further affect innate
immune function.1 Thus, any short-term symptom reduction from high
levels of vitamin D that may occur is probably occurring at the
cost of long-term pathogen increase. This has been supported by
observations of patient's responses over time. In the short-term,
even for ten years or more in some cases, the person may feel better
with high vitamin D intake. But in the long-term, the chronic infection
progresses, because the high 25-D is only adding to the bacterial
blockage of the VDR and the suppression of bacterial killing.18
Symptoms increase when the immune system is better able to kill
the pathogens, due to the high levels of inflammatory cytokine levels
that occur. This is called the immunopathological reaction or Jarisch-Herxheimer
reaction.6,11 The symptoms range from pain and fatigue to cognitive
impairment and depression, but include numerous other symptoms characteristic
of the underlying inflammatory condition.6,11 By suppressing the
immune response, vitamin D supplementation may suppress these symptoms
in the short-term and may even result in a sort of dependence on
vitamin D supplementation or sun exposure to keep the symptoms at
The long-term efficacy of the protocol (sometimes called the Marshall
Protocol or MP) in activating the VDR is also supported by improved
or stabilized bone density, which is typical in patients on the
protocol, if the RDA of calcium is consumed. The protocol replaces
vitamin D supplementation with use of the VDR agonist olmesartan
(120 to 160 mg in divided doses) and reduces the level of bacteria
blocking the VDR with antibiotics and, in this way, is apparently
effective in activating the VDR.6,12
Marshall proposes that vitamin D receptor blockage results in the
low levels of 25-D that have been observed in numerous diseases.
The precursor, 25-D form is the form that is most frequently measured.
The VDR blockage typically leads to dysregulation of metabolite
levels, and one effect is down-regulation of the conversion of vitamin
D to 25-D.1 Thus, according to this perspective, low 25-D levels
are the result, not a cause, of the disease process. It follows
that a low serum 25-D is not indicative of a true vitamin D deficiency
in this situation. Both laboratory19 and clinical findings20 have
supported the existence of an apparently similar type of down-regulation
of conversion to 25-D.
At the same time that low 25-D is observed, high 1,25-D levels are
also usually observed. In fact, elevated 1,25-D has been shown to
be a good indicator of inflammatory and autoimmune disease.13,16
When interpreting the results, however, it should be remembered
that samples must be frozen until analyzed for accurate 1,25-D results.
And occasionally, in cases of quite advanced disease or elderly
patients, 1,25-D will be low as well, yet still be consistent with
VDR blockage and inflammatory disease.21
Marshall's protocol was first used to treat sarcoidosis. It is well
established that a dysregulation of vitamin D levels, often with
very high 1,25-D and low 25-D, occurs in this condition.22 Marshall's
and other's work has confirmed that this dysregulation also occurs
in a wide range of other diseases.12,13,23,24 This pattern of high
1,25-D and low 25-D also exists in VDR knockout mice.25 These mice
are genetically engineered to lack a VDR, a situation analogous
to a bacteria-blocked VDR.
The very complex relationships among genes, metabolites, enzymes,
and receptors that Marshall recently summarized1,6 show that vitamin
D is not a mere nutrient. In fact, the active form is a secosteroid
transcriptional factor. It is part of a highly regulated and complex
system influencing many aspects of metabolism and immune function.
There are several feedback and feedforward pathways that influence
the levels of various vitamin D forms that Marshall reviewed in
Marshall was recently invited to co-chair a session on vitamin D
at the 6th Annual International Autoimmunity Conference, and he
gave one of the keynote presentations of the session.6 Several other
presentations were given that support the protocol and model. For
example, Perez presented data on treatment response in 20 autoimmune
conditions that support Marshall's model.11 The autoimmune diseases
successfully treated in this open-label trial include rheumatoid
arthritis, systemic lupus erythematosis, diabetes type 1 and 2,
psoriasis, Hashimoto's thyroiditis, Sjogren's syndrome, scleroderma,
uveitis, myasthenia gravis, and ankylosing spondylitis. Chronic
fatigue syndrome and fibromyalgia were shown to respond to the protocol
in another presentation.17 And another study indicated that dysregulation
of nuclear receptors in the endometrium by vitamin D, along with
chronic bacterial infection, can help explain the higher prevalence
of some autoimmune diseases in women.26
and Short-Term Clinical and Experimental Data
The in silico and clinical data discussed above provide strong evidence
for Marshall's model, and some might argue it is more reliable than
epidemiological and short-term evidence. It is widely recognized
that there are many limitations inherent in epidemiological and
short-term experimental data due to difficulties in obtaining relevant
and accurate results. Confounding factors and the inability to assess
the effects of long-term immune suppression from high levels of
vitamin D make the results less reliable.13,21 Experiments
using animal models have the problem of genetic differences and
different disease causation methods.1,13 Studies of supplementation
are often not randomized and thus are subject to unknown confounding
factors that may affect the choice to take vitamin D supplements.13
Furthermore, sun exposure is hard to quantify and is often left
out of the analyses. Any of the above can lead to invalid conclusions.
Despite this, a number of recent studies that may be relevant will
be discussed here to show that there is much independent support
for Marshall's model among these types of studies. In addition,
some lesser-known aspects of some of the studies used to support
a high vitamin D intake will be reviewed, which cast doubt on some
of their conclusions.
Cancer and All-Cause
In the case of cancer prevention, a recent randomized controlled
trial of calcium and vitamin D by Lappe et al.27 is used
to support vitamin D supplementation. However, it has a number of
serious limitations. One problem is the assumption that removing
the data from the first year is justified. If one looks at Figure
1, in the article by Lappe et al,27 in which the
data from the first year was included, there is very little difference
between calcium and vitamin D vs. calcium alone throughout the study
period. No group of patients was given vitamin D alone. Also, there
is not yet long-term data on incidence, since the study lasted only
four years. Any reduced incidence may reflect delay in diagnosis.
In addition, long-term survival may not ultimately improve. In fact,
patients taking vitamin D might even die sooner (see below). In
addition to the above critique, a number of published comments have
also taken issue with this trial, pointing to other problems and
Another recent study29 reported finding barely significant
lower cancer rates in premenopausal women (95% confidence interval,
0.42-1.0) who consumed more vitamin D. However, they found a marginally
significant higher rate of moderately differentiated tumors in postmenopausal
women who had higher vitamin D intake. And since postmenopausal
women make up a much higher proportion of breast cancer cases, this
is particularly concerning. This is just one example of the rather
inconclusive, mixed data on vitamin D supplementation that becomes
apparent when the vitamin D studies are looked at as a whole (see
Discussion section in ref. 29). Even the benefit for premenopausal
women is questionable. Bertone-Johnson et al.30 pointed
out a quite plausible rationale for the existence of a bias toward
low estrogen in those who choose to take vitamin D supplements.
A number of limitations found in the other studies are used as a
basis for supporting vitamin D supplementation. For instance, the
data is rarely long-term enough and rarely covers all the effects
possible. Although there may be an appearance of benefit in the
short-term or for subsets of the populations studied, a large, long-term
prospective study showed no effect of 25-D on the overall cancer
mortality rate in the long-term.31 Freedman et al.31
even showed a suggestion of a negative effect of higher vitamin
D levels. There was a non-significant increase in overall mortality
in the two groups with 25-D at higher levels (80 to <100 nmol/L:
Risk Ratio = 1.21, 95% CI =0.83 to 1.78; =100 nmol/L: Risk Ratio
= 1.35; 95% CI = 0.78 to 2.31, where 100 nmol/L corresponds to about
This is in accord with a study in prostate cancer32 (also
see discussion in ref. 21) and one in pancreatic cancer33
that found higher cancer rates when 25-D was high. Cancer rates
increased among patients with a 25-D level above approximately 32
ng/ml. Evidence regarding solar radiation and geographical/latitudinal
analyses are also used as evidence, yet solar radiation has many
other effects besides raising 25-D.34,35 Many other relevant
factors, such as pathogen distributions, climate effects on pathogen
spread36,37 and host susceptibility,38 diet,
and pollution levels also vary with geographical location.
It was recently pointed out in the Bulletin
of the World Health Organization that high 25-D has been
found to be associated with greater cancer risk in some studies.39
Studies mentioned, included one that found that there was a higher
rate of many internal cancers in patients who have a type of skin
cancer that is considered to be the best indicator of long-term
sun exposure.40 Another study discussed failed to find
a geographical pattern that would support a protective effect of
increased 25-D.41 On the whole, in these epidemiological
studies, the data is mixed and inconsistent, which is to be expected
when there are so many unknown confounding factors affecting 25-D
levels and disease incidence that may bias the results.13
In addition, a recent large prospective study presented evidence
suggesting that circulating 25-D concentrations may be associated
with increased risk of aggressive prostate cancer.42
For all types of prostate cancer, the data failed to support the
hypothesis that higher vitamin D decreases prostate cancer risk.42
Studies looking at overall mortality benefits of vitamin D are sometimes
misleading at first glance. In the large meta-analysis done recently
on the effect of vitamin D and calcium on mortality rates,43
the abstract attributes reduced mortality to vitamin D, yet the
only statistically significant results were for calcium together
with vitamin D. Another serious problem is that most of the studies
analyzed in the meta-analysis were only a few years in duration,
so long-term effects on mortality and morbidity could not be accurately
Bone Density, Parathyroid Hormone
Another area that should be re-evaluated is the negative association
between parathyroid hormone and 25-D levels. This association is
often used to assert that high levels of 25-D (e.g., 40 –50
ng/ml or more) are optimal. Aloia et al.44 has pointed
out that the studies that conclude these high levels of vitamin
D are needed fail to require adequate calcium intake, and that is
why such high levels are suggested. It should also be considered
whether both low 25-D and high PTH are due to the disease process
rather than the low 25-D causing the elevated PTH. In addition,
only a small percentage of patients with low 25-D have elevated
PTH. The low 25-D may be indicating a systemic chronic bacterial
infection, and the abnormally high PTH levels in a small percentage
of patients may merely be pointing to those cases in which bacteria
have infected the parathyroid gland to a greater degree.
In a study comparing vitamin D supplementation with calcium supplementation,45
"the effect of calcium on bone loss was blunted in subjects
with the highest levels of serum 25OH vitamin D [25-D]." This
last finding is supportive of Marshall's in silico work indicating
that high 25-D actually blocks the VDR.6,18 The largest
meta-analysis so far clearly showed benefit from calcium supplementation;
however, benefit for vitamin D was much less clear.46
No significant benefit for fracture risk was found when comparing
vitamin D and calcium to calcium alone, though some differences
were found between vitamin D levels.
Another factor that needs to be considered is whether immune suppression
is the cause of bone density improvement when high vitamin D levels
are used. Immunosuppressive drugs that lower TNF-alpha using antibodies
can improve bone density by reducing inflammation.47
High levels of vitamin D supplementation can also lower TNF-alpha48
and suppress the immune response. Thus, it is possible that an increase
in bone density from vitamin D supplementation could be the result
of immune suppression via TNF reduction, rather than correction
of a vitamin D deficiency. TNF-lowering drugs such as infliximab
(Remicade) increase risk of cancer and tuberculosis. Thus, the desirability
of improving bone density through immune suppression is questionable.
This immunosuppressive effect of vitamin D may even explain what
seems to be a beneficial effect on falls and muscle strength of
elevating vitamin D through supplementation.21 This may
be only a symptom reduction in the short-term and may be harmful
in the long-term due to the immune suppression.
In the area of autoimmune disease, the data is equally mixed, and
sometimes the larger, more recent studies fail to show any effect
of vitamin D levels. For example, a recent large study failed to
find an association between serum 25-D levels and the incidence
of systemic lupus erythematosis and rheumatoid arthritis.49 Research
has found that the average age at which patients acquired rheumatoid
arthritis is 12 years earlier in Mexico than in Canada and pointed
to the possible role of infectious agents in causing the disease.50
And clearly this study does not support the idea that sun exposure
is beneficial for rheumatoid arthritis, since Mexico gets far more
sun than Canada.
Although some studies in type 2 diabetes have indicated vitamin
D supplementation may be preventive,51 these studies were not randomized
and thus are subject to many known and unknown confounding factors
affecting a parent's decision to give a child supplemental vitamin
D.13 And even if it were clearly established that vitamin D supplementation
reduced the incidence of diabetes in infants and small children,
that would not mean that it would help in established disease or
older patients, nor would it necessarily mean it is the optimal
way to achieve diabetes prevention and long-term health. The positive
response of both type 1 and type 2 diabetes patients to the Marshall
Protocol11 indicates research on the role of bacteria in diabetes
should be a priority.
Influenza and Colds
It has been proposed that vitamin D levels' decline in winter best
accounts for the seasonality of colds and influenza52 and that this
potentially supports the need for increased supplementation.52,53
However, new evidence indicates that changes in the viral coat properties
can account for the seasonal outbreaks at higher latitudes.36,37
Effects on the airways in dry, cold climates also appear to increase
susceptibility to viral and bacterial infections in winter and could
contribute to higher winter prevalence of respiratory infections
in cold climates.38
Another important point is that the patients being followed on the
Marshall Protocol include a number of individuals who report that
during the worst period of their chronic illness, they had few or
no colds or flu-like illnesses, sometimes for many years at a time.
And sometimes this low rate of colds was apparent even years before
their illness. This has also been reported in Parkinson's disease,
with the decrease in viral respiratory infections also occurring
several years before the disease was diagnosed.54 Thus, even if
future research were to establish that vitamin D supplementation
reduced colds and influenza, this is by no means an adequate argument
for its use. The above observations in chronically ill patients
indicate that observing a reduction in respiratory viral infections
is not always a sign of good overall health.
Long-Term Negative Effects of Vitamin D Supplementation
Brannon et al.55 pointed out in a recent report from a roundtable
discussion of vitamin D data needs that many studies so far have
not yet adequately investigated potential negative consequences
such as soft tissue calcification. Vitamin D has been implicated
in arterial calcification in the past56 as well as other negative
effects.13 The report by the roundtable of vitamin D experts expressed
concern that many studies may be shortsighted with regard to adverse
A disturbing new study showed a highly significant correlation (p=0.007)
between increased vitamin D intake from food and supplements and
the volume of brain lesions shown by MRI in elderly adults.57 In
the multivariable regression model, vitamin D intake retained its
significant correlation with brain lesion volume even after the
effects of calcium were statistically removed. However, calcium
did not retain a significant independent correlation with the lesions
when the study controlled for vitamin D. Thus, the analysis points
to vitamin D supplementation as the key factor in higher lesion
volume in this study. These types of brain lesions have been linked
to adverse effects in many studies, e.g., stroke,58 psychiatric
disorders,59,60 brain atrophy,61 and earlier death.62 Interestingly,
the levels of vitamin D intake were not particularly high by some
standards, with the highest intake estimated at 1015 mg daily (mean
of 341 mg), about half coming from supplements and the rest from
The correlation between vitamin D intake and brain lesions seems
to lend further support to Marshall's work. In another study, the
finding that over a three-year period, a small percentage of patients
were found to have a slight regression of their brain lesions,63
leaves room for hope that the lesions are potentially reversible.
Reversibility would be in accord with the improvement of depression
and cognitive deficits and other neurological symptoms reported
in patients on the Marshall Protocol.6,64
Pathogens Are Detected with Improved Methods
Over many decades, researchers have reported evidence that hard-to-detect
bacterial infections are the cause of many diseases,65,66 including
autoimmune disease,65-68 cardiovascular disease,69-71 and even cancer.72-77
Some have noted the recent trend toward finding more infectious
causes of disease and suggested this is likely to increase in the
Recently, Barry Marshall received the Nobel Prize for discovering
that the bacteria Helicobacter pylori causes ulcers. And it is now
known that H. pylori is a causal factor in stomach cancer.77
New techniques using 16s ribosomal RNA shotgun sequencing,81,82
as well as more advanced culturing and observational techniques65,66,80,83-85
are suggesting that, up until now, most microbiologists have failed
to detect a large percentage of potential disease-causing agents.
"Persister" cells have been identified that escape antibiotic
treatment.86 Cell wall deficient organisms have long been studied,65-66
and just recently, advances have been made in understanding their
structure and in culturing techniques.80 Research is also indicating
that a bacterial biofilm-like microbiota of multiple species even
exists within human cells.6,8
Bacteria that grow on a surface in a multi-species community, protected
by both a biofilm and the combined effect of their individual resistance
strategies, have been a growing area of research.79 Bacterial biofilms
have been found to cause the non-healing ulcers in diabetics and
may be successfully treated using novel approaches, thus reducing
the need for limb amputation.88
Other examples of studies detecting unexpected bacterial pathogens
include work linking pathogens in amniotic fluid to pre-term birth89
and research showing numerous previously undetected species in the
biofilms that coat prosthetic hip joints.82 Many species of bacteria
have been in wounds that were previously undetected using older
techniques.81 Macfarlane et al.90 used a combination of more advanced
techniques to study bacteria in biofilm communities in patients
with Barrett's esophagus, a pre-cancerous condition. Their methods
revealed significant differences between patients and controls in
the types and numbers of bacterial species, differences that were
previously undetected using older techniques.
Increasingly, inflammation is observed in chronic diseases ranging
from depression to cardiovascular disease and cancer.87 The above
trends, when combined with observations of bacteria in numerous
diseases6,13,65,66,71,91 and the success of the anti-bacterial
protocol developed by Marshall6,8,11,13 suggest an extensive
role for previously unidentified chronic bacterial infections.
Research is also supporting the ineffectiveness of most standard
antibiotic protocols against these bacteria70 and suggesting why
other approaches may work better. For instance, some antibiotics
target cell walls, and this actually promotes the production of
cell wall deficient forms of bacteria that resist many antibiotics.80
Furthermore, many antibiotics are known to inhibit phagocytosis
and other aspects of the immune response when taken at high, constant
The ability of bacteriostatic antibiotics such as clindamycin to
be effective at low doses has been documented.93,94 The survival
of "persister" cells mean that pulsed antibiotics are
likely to be more effective.86 And fascinating investigations of
biofilm communities have revealed many ways in which bacteria can
resist antibiotics when used in traditional ways.95 The existence
of communities of many bacterial species means that combinations
of antibiotics are probably needed to be effective against all the
species present. Thus, there is increasing support for the use of
pulsed, low dosages of combinations of bacteriostatic antibiotics
as used in the anti-bacterial protocol discussed here.
What is particularly encouraging is that the effectiveness of Marshall's
protocol in many systemic chronic disease indicates that these elusive
pathogens do respond to select currently available bacteriostatic
antibiotics when innate immune function is restored through restoring
vitamin D receptor function.6,11 Not only do the bacterial infections
appear to resolve, the evidence so far suggests that the improved
immune response leads to reduced viral, fungal, and protozoal infections
In silico and clinical data indicate that it is likely that associations
between low vitamin D levels and chronic diseases are not evidence
of deficiency, but result from a bacteria-induced blockage of the
vitamin D receptor, leading to down-regulation of 25-D levels.1,6
According to this model of chronic disease, the short-term benefits
sometimes perceived with high vitamin D levels are not due to correction
of a vitamin D deficiency but due to suppression of bacterial killing
and the immunopathological reaction that accompanies it. Data on
reversal of a range of inflammatory and autoimmune diseases through
an anti-bacterial protocol that includes vitamin D avoidance and
a VDR agonist support this view.6,11
As discussed in detail above, it appears that increasing vitamin
D supplementation is not the answer to these chronic diseases and
is likely to be counter-productive. Other researchers have also
raised concerns regarding vitamin D supplementation's potential
adverse effects. Potential dangers include increased aortic calcification55,56
and brain lesions shown by MRI57 (also see above). In addition,
some studies have even found evidence of increased danger from cancer
in association with higher levels of vitamin D.32,33,39,40,42
Many have been attracted to the area of vitamin D research, recognizing
interesting patterns and responses to supplementation that at first
seemed to indicate widespread deficiency and, at the very least,
indicate that vitamin D plays a powerful role in physiological processes.
Great strides have been made in the last 30 years by scientists
with a range of perspectives, and this has led to great excitement
and a laudable commitment to use that knowledge to help patients.
However, new genomic and molecular research and the positive response
to a new anti-bacterial protocol that involves the avoidance of
vitamin D indicate the need for a reappraisal of the data gathered
so far. It appears that attempting to raise 25-D through vitamin
D supplementation or sun exposure is not the right approach to many,
if not most, common chronic diseases. Instead, as discussed above,
the evidence supports the effectiveness of a new protocol in restoring
vitamin D receptor function, which appears to be a crucial factor
One of the most commendable attributes of a truly objective scientist
is the willingness to be open to changing long-held positions in
the light of new evidence. It will be interesting to see how many
have this all-too-rare quality, as research and discussion of vitamin
D and the VDR continues. It is to be hoped that the tremendous healing
potential likely to be available from eliminating the pathogens
that cause chronic disease will inspire an especially high level
of open-minded discussion and cooperation.
immunopathological reactions from killing the high levels of bacteria
that have accumulated in chronically ill patients can be severe
and even life-threatening, and thus the Marshall Protocol must be
done very carefully and slowly, according to the guidelines.7,96
For the sake of safety, antibiotics must be started at quite low
dosages, starting with only one antibiotic. Health care providers
are responsible for the use of this information. Neither Autoimmunity
Research, Inc., nor the author assume responsibility for the use
or misuse of this protocol.
the author, Prof. Marshall, nor the non-profit Autoimmunity Research,
Inc. have any financial connection with any product or lab mentioned
with regard to the Marshall Protocol. The information needed to
implement the Marshall Protocol is available free of charge from
Joyce Waterhouse, PhD, graduated from
the University of California, Irvine, cum laude and Phi Beta Kappa,
with a bachelor's in Biology. Dr. Waterhouse received a PhD in Systems
Ecology with a minor in Statistics from the University of Tennessee,
Knoxville. She then pursued postdoctoral research at Oak Ridge National
Laboratory. Since 1997, she has written for and edited an online
newsletter focused on chronic illness: CISRA's
Synergy Health Newsletter (http://SynergyHN.com).
She has written a number of articles for peer-reviewed journals,
written a chapter in the book, Vitamin
D: New Research, and is currently a volunteer Research Scientist
with the non-profit Autoimmunity Research, Inc.
(For further links to Dr. Marshall's papers and presentations and
those of his colleagues, see: http://marshallprotocol.com/forum2/2274.html)
(1) Marshall TG. Vitamin D discovery outpaces FDA decision making.
2008; 30:173-82. Available at: http://trevormarshall.com/BioEssays-Feb08-Marshall-Preprint.pdf)
(2) Kimball SM, Ursell MR, O'Connor P, Vieth R. Safety of vitamin
D3 in adults with multiple sclerosis. Am
J Clin Nutr. 2007;86(3):645-51.
(3) Cutolo M, Otsa K, Laas K, Yprus M, Lehtme R, Secchi ME, Sulli
A, Paolino S, Seriolo B. Circannual vitamin D serum levels and disease
activity in rheumatoid arthritis: Northern versus Southern Europe.
Clin Exp Rheumatol.
(4) Cutolo M. Vitamin D and autoimmune rheumatic diseases. 6th International
Congress on Autoimmunity, Porto, Portugal, 2008.
(5) Goldberg P, Fleming MC, Picard EH. Multiple sclerosis: decreased
relapse rate through dietary supplementation with calcium, magnesium
and vitamin D. Med Hypotheses.
(6) Marshall TG. Presentation. VDR receptor competence induces recovery
from chronic autoimmune disease, 6th International Congress on Autoimmunity,
Porto, Portugal. 2008, (video: available at: http://vimeo.com/1787405).
(7) Waterhouse JC. The Marshall Protocol for Lyme disease and other
chronic inflammatory conditions: Part One. Overview and implementation.
2007 Mar;285:85-92. (8) Waterhouse JC. The Marshall Protocol for
Lyme disease and other chronic inflammatory conditions, Part Two:
Scientific background, data, and case histories. Townsend
Letter. 2007 Apr;286:84-90.
(9) Davis CD. Vitamin D and cancer: current dilemmas and future
research needs. Am J Clin Nutr.
(10) Mordan-McCombs S, Valrance M, Zinser G, Tenniswood M, Welsh
J. Calcium, vitamin D and the vitamin D receptor: impact on prostate
and breast cancer in preclinical models. Nutr
Rev. 2007 Aug;65(8 Pt 2):S131-3.
(11) Waterhouse JC, Perez TH, Albert P, Proal A. Presentation. Bacteria-induced
vitamin D receptor dysfunction in autoimmune disease: theoretical
and practical implications for interpretation of serum vitamin D
metabolite levels, 6th International Congress on Autoimmunity, Porto,
Portugal, 2008. (Video: Available at: http://vimeo.com/1789735.
Data: Available at :http://marshallprotocol.com/MP_results_chart.jpg)
(12) Marshall TG, Marshall FE. Sarcoidosis succumbs to antibiotics
– Implications for autoimmune disease. Autoimmun
Rev. 2004; 3(4):295-300.
(13) Waterhouse JC, Marshall TG, Fenter B, Mangin M, Blaney G. High
levels of active 1,25-dihydroxyvitamin D despite low levels of the
25-hydroxyvitamin D precursor – Implications of dysregulated
vitamin D for diagnosis and treatment of chronic disease. In: Stoltz
VD, ed. Vitamin D: New Research.
New York: Nova Science Publishers; 2006:1-23.
(14) Arasaki K. Presentation. Report on a case of systemic sarcoidosis
treated according to the Marshall Protocol. The 26th Conference
of the Japan Society of Sarcoidosis and Other Granulomatous Diseases.
Oct. 2006, Available at: http://autoimmunityresearch.org/transcripts/arasaki_jssog_2006.pdf.
(15) Brahmachary M, Schönbach C, Yang L, Huang E, Tan SL, Chowdhary
R, Krishnan SP, Lin CY, Hume DA, Kai C, Kawai J, Carninci P, Hayashizaki
Y, Bajic VB. Computational promoter analysis of mouse, rat and human
antimicrobial peptide-coding genes. BMC
Bioinformatics. 2007; 18;7
(16) Blaney GP. Presentation. Vitamin D metabolites as clinical
markers in autoimmune and chronic illness, 6th International Congress
on Autoimmunity, Porto, Portugal, 2008. (Video: Available at: http://vimeo.com/1790302.)
(17) Mangin M. Presentation. Monitoring recovery from autoimmune
disease with an interactive, internet-based clinical trial based
on a molecular model of chronic disease. 6th International Congress
on Autoimmunity, Porto, Portugal, 2008.
(18) Marshall TG. VDR nuclear receptor competence is the key to
recovery from chronic inflammatory and autoimmune disease. Presentation.
Days of Molecular Medicine 2006. Available at: http://autoimmunityresearch.org/karolinska-handout.pdf.
(19) Reinholz GG, DeLuca HF. Inhibition of 25-hydroxyvitamin D3
production by 1, 25-dihydroxyvitamin D3 in rats. Arch
Biochem Biophys. 1998;355:77-83.
(20) Bell NH, Shaw S, Turner RT. Evidence that 1,25-dihydroxyvitamin
D3 inhibits the hepatic production of 25-hydroxyvitamin D in man.
J Clin Invest.
(21) Waterhouse JC. Vitamins D in chronic disease. Presentation.
Recovery from Chronic Disease Conference, Autoimmunity Research
Inc., Los Angeles, California, 2006. Available at: http://autoimmunityresearch.org/transcripts/waterhouse_lax2006.pdf.
(22) Fauci A, et al, eds. Harrison's
Principles of Internal Medicine.
New York: McGraw Hill; 1997.
(23) Abreu MT, Kantorovich V, Vasiliauskas EA, Gruntmanis U, Matuk
R, Daigle K, Chen S, Zehnder D Lin Y-C, Yang H, Hewison M, Adams
JS. Measurement of vitamin D levels in inflammatory bowel disease
patients reveals a subset of Crohn's disease patients with elevated
1,25-dihydroxyvitamin D and low bone mineral density. Gut.
(24) Muller K, Kriegbaum NJ, Baslund B, Sorensen OH, Thymann M,
Bentzen K. Vitamin D3 metabolism in patients with rheumatic diseases:
low serum levels of 25-hydroxyvitamin D3 in patients with systemic
lupus erythematosus. Clin Rheumatol.
(25) Yoshizawa T, Handa Y, Uematsu Y, Takeda S, Sekine K, Yoshihara
Y, Kawakami T, Arioka K, Sato H, Uchiyama Y, Masushige S, Fukamizu
A, Matsumoto T, Kato S.
Mice lacking the vitamin D receptor exhibit impaired bone formation,
uterine hypoplasia and growth retardation after weaning. Nat
Genet. 1997 Aug;16(4):391-6.
(26) Proal A. Presentation. Vitamin D induced dysregulation of nuclear
receptors may account for higher prevalence of some autoimmune diseases
in women, 6th International Congress on Autoimmunity, Porto, Portugal,
2008. (Video: Available at: http://vimeo.com/1788640.)
(27) Lappe JM, Travers-Gustafson D, Davies KM, Recker RR. Heaney
RP. Vitamin D and calcium supplementation reduces cancer risk: results
of a randomized trial. Am J Clin
Nutr. 2007 Jun;85(6):1586-91.
(28) Schabas R. Artifact in the control group undermines the conclusions
of a vitamin D and cancer study. Am
J Clin Nutr. 2008 Mar;87(3):792;
author reply 793-4. Comment on: Am
J Clin Nutr. 2007 Jun;85(6):1586-91.
(29) Lin J, Manson JE, Lee IM, Cook NR, Buring JE, Zhang SM. Intakes
of calcium and vitamin D and breast cancer risk in women. Arch
Intern Med. 2007;167(10):1050-1059.
(30) Bertone-Johnson ER. Prospective studies of dietary vitamin
D and breast cancer: more questions raised than answered. Nutr
Rev. 2007 Oct;65(10):459-66.
(31) Freedman DM, Looker AC, Chang SC, Graubard BI. Prospective
study of serum vitamin D and cancer mortality in the United States.
J Natl Cancer Inst. 2007
(32) Tuohimaa P, Tenkanen L, Ahonen M, Lumme S, Jellum E, Hallmans
G, Stattin P, Harvei S, Hakulinen T, Luostarinen T, Dillner J, Lehtinen
M, Hakama M. Both high and low levels of blood vitamin D are associated
with a higher prostate cancer risk: A longitudinal, nested case-control
study in the Nordic countries. Int
J Cancer. 2004; 108:104-8.
(33) Stolzenberg-Solomon RZ, Vieth R, Azad A, Pietinen P, Taylor
PR, Virtamo J, Albanes D. A prospective nested case-control study
of vitamin D status and pancreatic cancer risk in male smokers.
(34) Lucas RM, Ponsonby AL. Considering the potential benefits as
well as adverse effects of sun exposure: can all the potential benefits
be provided by oral vitamin D supplementation? Prog
Biophys Mol Biol. 2006 Sep;92(1):140-9.
(35) Steindal AH, Porojnicu AC, Moan J. Is the seasonal variation
in cancer prognosis caused by sun-induced folate degradation? Med
(36) Lowen AC, Steel J, Mubareka S, Palese P. High temperature (30
degrees C) blocks aerosol but not contact transmission of influenza
virus. J Virol.
(37) Lowen AC, Mubareka S, Steel J, Palese P. Influenza Virus Transmission
Is Dependent on Relative Humidity and Temperature. PLoS
Pathog. 2007 Oct; 3(10):1470-6.
(38) Kalkstein LS, Valimont KM. Climate effects on human health.
In Potential effects of future climate changes on forests and vegetation,
agriculture, water resources, and human health. 1987. EPA Science
and Advisory Committee Monograph no. 25389, 122-52. Washington,
D.C.: US Environmental Protection Agency. Available at: http://www.ciesin.org/docs/001-338/001-338.html
(39) Lucas RM, Repacholi MH, McMichael AJ. Author Response to Comment.
Bull World Health Organ. 2007; 85:325. Available at: https://www.who.int/bulletin/volumes/85/5/06-039446/en/print.html.
(40) Efird JT, Friedman GD, Habel L, Tekawa IS, Nelson LM. Risk
of subsequent câncer following invasive or in situ squamous
cell skin cancer. Ann Epidemiol.
2002; 12: 469-75.
(41) Diffey B. Do we need a revised public health policy on sun
exposure? Br J Dermatol
2006; 154: 1046-51.
(42) Ahn J, Peters U, Albanes D, Purdue MP, Abnet CC, Chatterjee
N, Horst RL, Hollis BW, Huang WY, Shikany JM, Hayes RB. Serum vitamin
D concentration and prostate cancer risk: a nested case-control
study. J Natl Cancer Inst.
2008 Jun 4;100(11):796-804.
(43) Autier P, Gandini S. Vitamin D supplementation and total mortality:
a meta-analysis of randomized controlled trials.
Arch Intern Med. 2007 Sep
(44) Aloia JF, Talwar SA, Pollack S, Feuerman M, Yeh JK. Optimal
vitamin D status and serum parathyroid hormone concentrations in
African American women. Am J Clin
Nutr. 2006 Sep;84(3):602-9.
Available at: http://www.ajcn.org/cgi/content/full/84/3/602.
(45) Peacock M, Liu G, Carey M, McClintock R, Ambrosius W, Hui S,
et al. Effect of calcium or 25OH vitamin D3 dietary supplementation
on bone loss at the hip in men and women over the age of 60. J
Clin End Metab. 2000; 85(9),
(46) Tang BM, Eslick P, Nowson GB, Smith C, Bensoussan A. Use of
calcium or calcium in combination with vitamin D supplementation
to prevent fractures and bone loss in people aged 50 years and older:
a meta-analysis. Lancet.
(47) Lange U, Teichmann J, Müller-Ladner U, Strunk J. Increase
in bone mineral density of patients with rheumatoid arthritis treated
with anti-TNF-alpha antibody: A prospective open-label pilot study.
(48) Schleithoff SS, Zittermann A, Tenderich G, Berthold HK, Stehle
P, Koerfer R. Vitamin D supplementation improves cytokine profiles
in patients with congestive heart failure: a doubleblind, randomized,
placebo-controlled trial. Am J Clin
Nutr. 2006 Apr;83(4):754-9.
Available at: http://www.ajcn.org/cgi/content/full/83/4/754.
(49) Costenbader KH, Feskanich D, Holmes M, Karlson EW, Benito-Garcia
E. Vitamin D intake and risks of systemic lupus erythematosus and
rheumatoid arthritis in women. Ann
Rheum Dis. 2008 Apr;67(4):530-5.
(50) Ramos-Remus C, Sierra-Jimenez G, Skeith K, Aceves-Avila FJ,
Russell AS, Offer R, Olguin-Redes JE, Homik J, Sanchez L, Sanchez-Ortiz
A, Navarro-Cano G. Latitude gradient influences the age of onset
in rheumatoid arthritis patients. Clin
Rheumatol. 2007 Oct;26(10):1725-8.
(51) Ponsonby AL, Lucas RM, van der Mei IA. UVR, vitamin D and three
autoimmune diseases--multiple sclerosis, type 1 diabetes, rheumatoid
arthritis. Photochem Photobiol.
(52) Cannell JJ, Vieth R, Umhau JC, Holick MF, Grant WB, Madronich
S, Garland CF, Giovannucci E. Epidemic influenza and vitamin D.
Epidemiol Infect. 2006;134:1129–1140.
(53) Aloia JF, Li-Ng M. Re: epidemic influenza and vitamin D. Epidemiol
Infect. 2007 Oct;135(7):1095-6, Comment on: Epidemiol
Infect. 2006 Dec;134(6):1129-40.
(54) Kawaguchi N, Yamada T, Hattori T. Rare tendency of catching
cold in Parkinson's disease. Parkinsonism
Relat Disord. 1998 Dec;4(4):207-9.
(55) Brannon PM, Yetley EA, Bailey RL, Picciano MF. Summary of roundtable
discussion on vitamin D research needs. Am
J Clin Nutr. 2008 Aug;88(2):587S-592S.
(56) Norman PE, Powell JT. Vitamin D, shedding light on the development
of disease in peripheral arteries. Arterioscler
Thromb Vasc Biol. 2005 Jan;25(1):39-46.
(57) Payne ME, Anderson JJB, Steffens DC. Calcium and vitamin D
intakes may be positively associated with brain lesions in depressed
and non-depressed elders. Nutr Res.
(58) Wen W, Sachdev PS. Extent and Distribution of White Matter
Hyperintensities in Stroke Patients.
Stroke. 2004; 35:2813. Available
(59) Lyoo IK, Lee HK, Jung JH, Noam GG, Renshaw PF. White matter
hyperintensities on magnetic resonance imaging of the brain in children
with psychiatric disorders. Compr
Psychiatry. 2002; Sep-Oct;43(5):361-8.
(60) Ahn KH, Lyoo IK, Lee HK, Song IC, Oh JS, Hwang J, Kwon J, Kim
MJ, Kim M, Renshaw PF. White matter hyperintensities in subjects
with bipolar disorder. Psychiatry
Clin Neurosci. 2004; Oct;58(5):516-21.
(61) Wen W, Sachdev PS, Chen X, Anstey K. Gray matter reduction
is correlated with white matter hyperintensity volume: a voxel-based
morphometric study in a large epidemiological sample. NeuroImage.
(62) Kerber KA, Whitman GT, Brown DL, Baloh RW. Increased risk of
death in community dwelling older people with white matter hyperintensities
on MRI. J Neurol Sci.
2006; 250(1-2), 33-8.
(63) Sachdev P, Wen W, Chen X, Brodaty H. Progression of white matter
hyperintensities in elderly individuals over 3 years. Neurology.
(64) Mangin M. Monitoring cognitively-disabled subjects in an interactive
Internet-based clinical trial of a multi-factorial treatment based
on a molecular model of chronic disease. Presentation, Days of Molecular
Medicine Conference, Karolinska Institut, Stockholm, Sweden, 2008.
(65) Mattman L. Cell Wall Deficient
Forms: Stealth Pathogens.
Boca Raton: CRC Press; 2000.
(66) Domingue G, Woody H. Bacterial persistence and expression of
disease. Clin Microbiol Rev.
(67) Shoenfeld Y, Isenberg DA. Mycobacteria and autoimmunity. Immunol
Today. 1988 Jun;9(6):178-82.
(68) Fredricks DN, Relman DA.Infectious agents and the etiology
of chronic idiopathic diseases. Curr
Clin Top Infect Dis.1998;18:180-200.
(69) Higuchi-Dos-Santos MH, Pierri H, Higuchi MD, Nussbacher A,
Palomino S, Sambiase NV, et al. Chlamydia pneumoniae and Mycoplasma
pneumoniae in calcified nodes of stenosed aorticvalves.]. Arquivos
Brasileiros de Cardiologia
2005; 84(6):443-8. Available at: http://tinyurl.com/37c58m
(70) Onwuamaegbu ME, Belcher RA, Soare C. Cell wall-deficient bacteria
as a cause of infections: a review of the clinical significance.
J Int Med Res 2005;
33(1):1-20. Available at: http://www.jimronline.net/content/full/2005/58/0545.pdf
(71) Cochran GM, Ewald PW, Cochran KD. Infectious causation of disease:
An evolutionary perspective. Perspect
Biol Med. 2000 Spring;43(3):406-48.
(72) Broxmeyer L. Is cancer just an incurable infectious disease?
2004 63(6), 986-96.
(73) Cohen RJ, Shannon BA, McNeal JE, Shannon T, Garrett KL. Propionibacterium
acnes associated with inflammation in radical prostatectomy specimens:
A possible link to cancer evolution? J.
(74) Cantwell AR Jr. Acid-fast bacteria in-vivo in prostate cancer
and the connection between prostate cancer, other cancers, and the
Kaposi's sarcoma virus. JOIMR
2004;2(3). Available at:: http://www.joimr.org/phorum/read.php?f=2&i=57&t=57.
(75) Cimolai N. Do mycoplasmas cause human cancer? Can
J Microbiol. 2001;47(8);691-7.
(76) Huan S, Li JY, Wu J, Meng L, Shou CC. Mycoplasma infections
and different human carcinomas. World
J Gastroenterol. 2001;7(2):266-9.
(77) de Martel C, Franceschi S. Infections and cancer: Established
associations and new hypotheses. Crit
Rev Oncol Hematol. 2008 Sep
19 [Epub ahead of print].
(78) O'Connor SM, Taylor CE, Hughes JM. Emerging infectious determinants
of chronic diseases. Emerg Infect
Dis. 2006 Jul;12(7):1051-7.
(79) Davey ME, O'Toole GA. Microbial biofilms: From ecology to molecular
genetics. Microbiol Mol Biol Rev.
(80) Casadesús J. Bacterial L-forms require peptidoglycan
synthesis for cell division, BioEssays.
(81) Dowd SE, Sun Y, Secor PR, Rhoads DD, Wolcott BM, James GA,
Wolcott RD. Survey of bacterial diversity in chronic wounds using
pyrosequencing, DGGE, and full ribosome shotgun sequencing. BMC
Microbiology. 2008; 8:43-58.
(82) Dempsey KE, Riggio MP, Lennon A, Hannah VE, Ramage G, Allan
D, Bagg J. Identification of bacteria on the surface of clinically
infected and non-infected prosthetic hip joints removed during revision
arthroplasties by 16S rRNA gene sequencing and by microbiological
culture. Arthritis Res Ther.
(83) Cantwell AR Jr, Cove JK. Variably acid-fast bacteria in a necropsied
case of systemic lupus erythematosus with acute myocardial infarction.
(84) Wirostko E, Johnson L, Wirostko W. Juvenile rheumatoid arthritis
inflammatory eye disease. Parasitization of ocular leukocytes by
mollicute-like organisms. J Rheumatol.
(85) Nilsson K, Pahlson C, Lukinius A, Eriksson L, Nilsson L, Lindquist
O. Presence of Rickettsia helvetica in granulomatous tissue from
patients with sarcoidosis. J Infect
Dis. 2002; 185:1128-38.
(86) Lewis K. Persister cells, dormancy and infectious disease.
Nat Rev Microbiol.
(87) Leonard BE. Inflammation, depression and dementia: are they
connected? Neurochem Res.
(88) James GA, Swogger E, Wolcott R, Pulcini E, Secor P, Sestrich
J, Costerton JW, Stewart PS. Biofilms in chronic wounds. Wound
Repair Regen. 2008 Jan-Feb;16(1):37-44.
(Also see interview, available at: http://bacteriality.com/2008/04/13/wolcott/.)
(89) DiGiulio DB, Romero R, Amogan HP, Kusanovic JP, Bik EM, Gotsch
F, Kim CJ, Erez O, Edwin S, Relman DA. Microbial prevalence, diversity
and abundance in amniotic fluid during preterm labor: a molecular
and culture-based investigation. PLoS
ONE. 2008 Aug 26;3(8):e3056.
(90) Macfarlane S, Furrie E, Macfarlane GT, Dillon JF. Microbial
colonization of the upper gastrointestinal tract in patients with
Barrett's esophagus. Clin Infect
Dis. 2007; 45:29–38.
(91) Pordeus V, Szyper-Kravitz M, Levy RA, Vaz NM, Shoenfeld Y.
Infections and autoimmunity: A panorama. Clin
Rev Allergy Immunol. 2008
(92) Labro M. Interference of antibacterial agents with phagocyte
functions: immunomodulation or "immuno-fairy tales"? Clin
Microbiol Rev. 2000;13(4):615-650.
(93) Milatovic D. Effect of subinhibitory antibiotic concentrations
on the phagocytosis of Staphylococcus aureus. European
J Clin Microbiol. 1982;1(2):97-101.
(94) Starner TD, Shrout JD, Parsek MR, Appelbaum PC, Kim G. Subinhibitory
concentrations of azithromycin decrease nontypeable Haemophilus
influenzae biofilm formation and diminish established biofilms.
Antimicrobial Agents Chemother.
(95) del Pozo JL, Patel R. The challenge of treating biofilm-associated
bacterial infections. Clin Pharmacol
Ther. 2007 Aug;82(2):204-9.
(96) Phase One Guidelines for Marshall Protocol. Available at: http://autoimmunityresearch.org/phase1.pdf .