In general, oxytocin makes people more sociable and less phobic.

Produced naturally in the brain during social interactions, the hormone oxytocin promotes romantic feelings. It’s also the hormone that helps mothers bond with babies and, in general, makes people more sociable and less phobic. Oxytocin is released during orgasm and is also the key birthing hormone that enables the cervix to open and the contractions to work. In situations where labor has to be induced, it is often given to the mother intravenously to kick-start contractions.

Indeed several recent trials have confirmed oxytocin’s “feel good” effects. After testing the hormone on hundreds of patients, Paul Zak of California’s Claremont Graduate University has concluded that its main effect is to curb the instincts of wariness and suspicion that cause anxiety. “It is a hormone that facilitates social contact between people,” argues Zak.

Data collected from the Marshall Protocol study site, as well as information garnered from numerous other clinical studies strongly suggests that people with Th1 disease are often more prone to developing phobias, OCD-like tendencies, and anxiety in general. Of course, there’s a fine line separating such tendencies from the natural feelings that build as a person attempts to deal with the strain of chronic disease. Understandably, chronically ill individuals feel a certain level of depression, anxiety, fear, suspicion, etc. as they try to understand and manage illnesses for which mainstream medicine offers little insight into cause, cure, or means to prevent deterioration.

But as people accumulate an increasing load of the chronic, intraphagocytic metagenomic bacteria that cause inflammatory disease (also called the Th1 pathogens), mental compulsions are directly caused by infection rather than a healthy person’s natural reaction to challenging life events. Many patients on the Marshall Protocol have admitted that they simply didn’t realize the extent of their infection-induced phobias until the symptoms return temporarily as part of the immunopathological response (bacterial die-off reaction). Anxiety, fear, the perception that something is “wrong” when it isn’t, or the feeling that people are conspiring against oneself is often heightened by immunopathology. This suggests that to a large extent, the mental compulsions of people with Th1 disease are not due to circumstance but are instead the result of bacterial infection.

Based on this knowledge, one might hypothesize that levels of oxytocin are often low in patients with chronic disease. And the assumption would be correct. Low levels of oxytocin in the blood have been detected in patients with chronic diseases ranging from sarcoidosis to autism. For example, autistic patients given oxytocin as part of a study in New York found their ability to recognize emotions such as happiness or anger in a person’s tone of voice – reactions that usually elude their mental abilities – improved.

The results of such studies have caused most mainstream researchers to simply write off chronically ill patients as “oxytocin deficient,” with little thought to why the hormone might be low in the first place. But the Marshall Pathogenesis and recent data on the Vitamin D Receptor allow for a reasonable hypothesis that explains why oxytocin is often low in chronic disease.

“The genes that allow for the transcription of the oxytocin receptor are transcribed by the Vitamin D Receptor.”According to researchers at McGill University in Canada, who recently created a database of VDR-target genes, the genes that allow for the transcription of the oxytocin receptor are transcribed by the Vitamin D Receptor. “And very strongly too,” adds biomedical researcher Trevor Marshall.

And there you have it. A small nugget of information allows for a deeper understanding of the pathways that contribute to compulsions and phobias at the molecular level. The Th1 pathogens create substances that dysregulate the Vitamin D Receptor, slowing its activity in the process. The higher a person’s pathogenic load, the more disabled their VDRs become. So as people accumulate the Th1 pathogens, they lose the ability to activate the receptor that would otherwise transcribe the genes necessary for oxytocin production. As transcription of the hormone slows, patients suffer the negative consequences, including an inability to effectively control paranoia, fear, social awkwardness, feelings of exclusion, depression, disconnect with others, and certain manias.

“Another piece of the puzzle falls into place,” Marshall concurs.

In my opinion, such knowledge offers hope when it comes to the future of human relations. Although bacterial load differs greatly from person to person, at the moment, every member of the population harbors at least some of the Th1 pathogens. And in countries where vitamin D supplementation is the norm, nearly everyone has a level of 25-D that is too high. Since elevated 25-D and bacterial ligands block the VDR and subsequently the production of the genes it transcribes, it’s quite possible that nearly everyone in the world currently has lower than normal oxytocin levels. Does that mean that all of us, to different degrees, are a little more anxious, less trusting, a bit more depressed than we would be if we had fully functioning VDRs?

If this is the case, large-scale restoration of VDR homeostasis might allow for a world more willing to compromise and put long held disputes to rest. The possibility is supported by a recent study in which scientists gave doses of oxytocin and a placebo to participants, who were then asked to decide how to split a sum of cash with a stranger. Those given oxytocin offered 80 per cent more money than those given a placebo. And previous research into the hormone by Professor Zak suggests that generous people had higher than average levels of oxytocin in the brain, while “mean-spirited people” have lower than normal levels.

The knowledge that oxytocin levels are regulated by the VDR is an example of knowledge that should allow doctors and researchers to draw a much more accurate line between personality traits and mental tendencies caused by disease. Take extreme shyness. Is extreme shyness simply a result of personality or might it also have an infectious component? In recent trials, researchers at Zurich University in Switzerland managed to ease symptoms of extreme shyness in 120 patients by giving them oxytocin treatment half an hour before they encountered an awkward situation. Such results can only be explained by changes in chemical balance rather than changes in personality, suggesting that, like other chronic mental issues, extreme shyness could result at least partly from infection. It’s of interest that a recent poll found that sixty percent of Britons say they have suffered from shyness, and one in 10 say it impedes their daily life. That’s quite a high prevalence of shyness, suggesting that like almost all other inflammatory diseases, shyness might be on the rise due to vitamin D supplementation, the increased use of immunosuppressant drugs, our sun-loving culture and other circumstances that compromise the integrity of the immune system.

Graeme Obree: deficient in oxytocin?

One could argue that in a world where compulsions can finally be treated, there may be circumstances in which a person would be upset if a mental trait they come to value disappears during recovery. Perhaps a person’s OCD-like tendencies allow them to train beyond the scope of others in order to win an athletic event. If such a person eliminates the pathogenic load in their head, will they still be able to train and compete with such fanaticism? Many would argue that the famous cyclist Graeme Obree, who set the hour record in cycling, was ironically driven to excellence by focusing on memories inspired by his severe depression. There may also be artists whose works are fueled by their phobias. If the MP had existed in the nineteenth century, Van Gogh might very well have become just another artist painting sanguine pictures. Yet when it comes to the majority of people struggling with social anxiety or battling mental compulsions, the ability of the MP to quell a variety of phobias is almost certainly appealing and liberating.

So far I’ve discussed scenarios in which, thanks to VDR activation, oxytocin is naturally able to return to a normal level – a process directed by the body’s own homeostatic mechanisms. Yet, as communicated in a recent article on oxytocin in the Evening Standard‘s website This is London, most researchers seem to have little interest keeping oxytocin levels in the range that would be maintained by a healthy body left to its own ways. Instead, driven by the standard “the more the better” mindset, they seem motivated by the prospects of high-dose oxytocin supplementation. It seems that just like the “experts” who weigh in on vitamin D supplementation, oxytocin proponents are giving little, if any, thought to the possible negative consequences of dousing ourselves with a hormone that under natural circumstances is tightly regulated by the body.

An oxytocin spray has just been successfully trialled at the University of New South Wales and experiments by Dr Eric Hollander at the city’s Mount Sinai School of Medicine found a single intravenous infusion of the chemical triggered improvements that lasted for two weeks. These studies, along with Zak’s work has researchers in the US, Europe and Australia racing to develop commercial forms of the hormone, including a nasal spray. Driven, no doubt in part by the monetary prospects involved in creating oxytocin-containing compounds, such scientists believe that oxytocin can be turned into a “wonder drug” capable of treating a range of personality disorders such as autism, depression and anxiety.

A wonder drug? Wow! I think I just heard the local newscaster regurgitate information about another so-called wonder drug… vitamin D! And whereas vitamin D is fondly coddled as the “sunshine vitamin,” oxytocin will soon be enthusiastically promoted as the “love drug.”

Most scientists seem to have few qualms about high-level oxytocin supplementation.

The comparison would be lovely, if only the view of vitamin D as a helpful “sunshine vitamin” were actually correct. Unfortunately, the majority of vitamin D “experts” have failed to realize that the palliation offered by vitamin D stems only from its ability to slow the innate immune response. So they are content to extol the virtues of the secosteroid’s short-term palliative effects with little regard to the long term immunosuppression – and subsequent rise in bacterial load – it causes when taken in excess.

Zak contends that oxytocin, “is a very safe product that does not have any side effects and is not addictive.” Quite frankly though, how can he pretend to know such information? Clinical studies alone can never reveal the mechanisms by which a compound actually works inside the body and generally do not detect long-term side effects. For example, based on the first generation of clinical and epidemiological studies alone, vitamin D supplementation seemed like an excellent idea. It wasn’t until Marshall used molecular modeling software to mathematically calculate the affinities of the various forms of the secosteroid/hormone for their target receptors that the deleterious effects of 25-D on innate immune function became apparent. So until a researcher succeeds in modelling the effects of the hormone at the molecular level, and proceeds to create a model of the metabolic pathways that regulate its production, it’s madness to think that supplementation with excess oxytocin can simply be assumed to have no negative effects.

Don’t get me wrong, I see possible uses for oxytocin if used in moderation. But the articles I’ve read on the hormone contain quotes from researchers exercising little, if any, caution. According to the Evening Standard‘s article, “The potential uses of oxytocin offer commercial possibilities well beyond individual patients.” Restaurants, for instance, could spray a thin mist over customers to put them at ease. Since researchers at Emory University in Atlanta recently released the results of a study which suggests that oxytocin made rodents more faithful to their partners, some believe that extra levels of oxytocin could be used to prevent extramarital affairs. Others have proposed that oxytocin supplementation could serve as a treatment for alcoholism. Still others argue that oxytocin could be used as a benign form of tear gas, quelling any violent feelings among groups of demonstrators. While it’s plausible that oxytocin spray might succeed in placating a rowdy crowd, does the government really want to disrupt the homeostatic hormonal feedback pathways of large groups of people? And remember the study mentioned above where people given oxytocin gave 80% more money to a stranger? While such generosity may be helpful under some circumstances, it’s possible that if people take too much oxytocin, they may lose their inhibitions to the point where they might give away things they really need. Even some mainstream researchers admit that oxytocin could have potential as a date-rape drug as it is involved in both trust and sexual arousal.

So how about returning to the first scenario discussed in this piece – the scenario in which the Marshall Protocol can be used to restore oxytocin levels to those set by nature. Not that a few extra puffs of oxytocin couldn’t be used under special circumstances, but like vitamin D, it seems to me that hormonal pathways function optimally when left alone.

Yet, I must share this parting thought: could oxytocin spray, if used very carefully, be used to counteract the symptoms of brain immunopathology during difficult times on the MP? While the goal of every MP patient is to allow their hormones to rebalance naturally, those patients who suffer from severe mental infection might be able to use oxytocin in moderation in order to relieve intolerable symptoms. One thing’s clear, when it comes to oxytocin, there remain more questions than answers.

In the following article, I discuss what I will be presenting at Karolinska.

In 2001, Alayne B. spent 8 months staring at a wall. “I went from being a company executive to barely being able to read above a 4th grade level,” states Alayne. “I couldn’t focus/concentrate on anything. My short-term memory turned into about 15 seconds – my nickname was ‘Memento Girl’ after the movie Memento.” The L.A. native would have to write notes immediately after a conversation or she’d forget what had been discussed. She also had to write herself notes in order to remember where she was driving. If she didn’t, she’d forget where she was going and get lost. “Ultimately I had to stop driving because I’d also forget that the notes were on the seat next to me and it’d take me ages to find my way home,” Alayne confesses. “I no longer had any mathematical figuring abilities either.”

Eventually, she started teaching at a private school – a job that was physically demanding, not to mention required increased brain use. “I made it through a few sessions, but would catch pneumonia, etc. and my energy levels were dropping again,” states Alayne. “Plus, I started forgetting words, how to spell, couldn’t understand my own lesson plans, couldn’t figure out the basic math I was also teaching, etc. When students caught a mistake, I’d pretend I’d been trying to catch them up – which they thought was fun. However, that only goes so far. I started teaching exclusively one-on-one in homes, but that also petered out, as I just couldn’t remember what the heck I was doing there.”

In 2005, Alayne was finally properly diagnosed with CFS. Her reading levels fell again to elementary/junior high level, her mathematical abilities to about 0, and her short term memory left her once again. She suffered from high levels of fear and anxiety, her word recall was horrible, and her reasoning abilities were greatly reduced. “I had no choice but to stop teaching even little one-hour tutoring sessions because I was confusing my students AND it would take me 5 days to recover from 3 hours spent away from home (driving, teaching, driving),” states Alayne.

Upon starting the Marshall Protocol in 2005, she was able to grasp enough of the treatment to “see it was the missing puzzle piece.” However, she could not explain it to anyone else, nor remember what she’d read. “I wrote a few notes down and went with it,” she describes. “By that time, I was bed-bound, emaciated, and my boyfriend and I thought I was dying.”

Although the CDC has recently recognized Chronic Fatigue Syndrome (CFS/ME) as a physiological disease, doctors and researchers are only beginning to understand the severe cognitive effects of the illness, such as those described by Alayne.

Alayne

Case histories like Alayne’s are supported by numerous studies that have tested the cognitive abilities of patients with CFS.

Take, for example, a 2007 twin study conducted by researchers at the University of Hawaii. After controlling for genetic and environmental influences, female identical twins, in which one twin met strict criteria for CFS and the co-twin was healthy, underwent a structured psychiatric interview and comprehensive neuropsychological assessment that evaluated 6 cognitive domains. Results indicated that twin groups had similar intellectual and visual memory functioning, but fatigued twins exhibited decreases in motor functions, speed of information processing, verbal memory, and executive functioning.

Similarly, researchers at the Department of Physical Medicine and Rehabilitation, University of Medicine and Dentistry of New Jersey, recently compared the cognitive performance of subjects with chronic fatigue syndrome (11 female subjects, 1 male subject), multiple sclerosis (MS), and healthy controls. After matching subjects for age, education, and verbal intelligence, subjects were given a battery of neuropsychological tests and scores were compared among the groups. Subjects with CFS and MS scored significantly below control subjects on five different tests that examined memory, concentration, word recall, information processing, and other cognitive abilities (CFS subjects scored worse than MS subjects on two of the tests).

“These results indicate that subjects with CFS and subjects with MS show significant impairment on a test of complex concentration when compared with appropriate controls,” state the research team. “The data suggest that subjects with CFS and subjects with MS have difficulty on tasks that require the simultaneous processing of complex cognitive information.”

Interestingly, the vast majority of studies that have tested for various forms of cognitive dysfunction in CFS patients, including those described above, contain only/mostly women as subjects. For starters, more women than men are diagnosed with the disease. In fact, CFS victims are twice as likely to be women.

But while males also suffer from CFS, the cognitive symptoms of women are, for the most part, reported to be more severe then those experienced by their male counterparts. This is not to say that some men with CFS can’t and don’t suffer from severe cognitive dysfunction, only that most of the studies that describe serious cognitive decline in CFS patients focus on women.

While I can’t deny that these studies may suffer from some forms of bias, the notion that women with CFS are more likely to suffer from severe cognitive dysfunction held up when I started research for this paper/presentation. Because I wanted to speak with cognitively impaired CFS patients on a one to one basis, I posted on the Marshall Protocol study site, asking if CFS patients who had suffered or were suffering from cognitive problems could send me an email describing their symptoms. While eight women contacted me, only one male patient volunteered information.

The endometrium

What might explain the hypothesis that women with CFS are more likely to experience serious cognitive dysfunction than their male counterparts? In what ways do men and women differ?

One obvious and rather large difference between men and women is that women have a uterus – an organ that has several internal membranes. One of these layers is the endometrium.

The endometrium is the inner membrane of the mammalian uterus.

The endometrium is the inner membrane of the mammalian uterus. It functions as a lining for the uterus, keeping the walls of the middle layer of the uterine wall separated – thereby maintaining the expanded shape of the uterine cavity.

During the menstrual cycle, the endometrium grows to a thick, blood vessel-rich, tissue layer that is filled with glands. This represents an optimal environment for the implantation of a blastocyst – the mass of cells that eventually forms an embryo if it arrives safely to the uterus.

If no blastocyst is detected, levels of the hormone progesterone (which is secreted in the endometrium) drops, and the endometrial lining is shed during what is known as the menstrual cycle. In the latter case, the process of shedding involves the breaking down of the lining, the tearing of small connective blood vessels, and the loss of the tissue and blood that had constituted it through the vagina. In humans, the cycle of building and shedding the endometrial lining lasts an average of 28 days.

If a blastocyst is able to implant, pregnancy results. In this case, the endometrial lining is neither absorbed nor shed. Instead, it remains as decidua. The decidua becomes part of the placenta; it provides support and protection for the embryo.

The endometrium produces certain hormones which affect other portions of the reproductive system and participate in important feedback pathways. This means that the endometrium is also home to a plethora of receptors whose activity is controlled by these hormones and other molecules.

The vitamin D system in the endometrium

In what is believed to be the first study to investigate the vitamin D system in human cycling endometrium, researchers at the Fondazione Policlinico-Mangiagalli-Regina Elena Hospital at the University of Milano in Italy have recently identified that one of the hormones produced in excess in the endometrium is the active vitamin D metabolite 1,25-D. Not surprisingly then, the research team also confirmed that both cycling and early pregnant endometrial cells express the Vitamin D Receptor (VDR), which is activated by 1,25-D.

One of the body’s most fundamental receptors, the VDR controls the activity of the innate immune system, or the body’s first line of defense against infectious agents. It also transcribes many antimicrobial peptides – peptides that kill bacteria, viruses, and fungi by a variety of mechanisms including disrupting membranes, interfering with metabolism, and targeting components of the machinery inside the cell.

Furthermore, the receptor activates the transcription of hundreds and possibly thousands of genes. Researchers at McGill University have compiled two lists of genes transcribed by the Vitamin D Receptor including 913 genes on the confirmed list and over 20,000 on the putative list. These genes are associated with genes ranging from cancers to multiple sclerosis.

The Italian team was able to gauge the presence and quantity of 1,25-D in the endometrium by using several different molecular methods to track levels of the enzyme 1{alpha}-hydroxylase (1-OHase) – or the enzyme that catalyzes the production of 1,25-D.

The team, under the leadership of P. Vigano, found that the endometrium harbors abundant quantities of 1,25-D, independent of the phase during which it is cycling under normal conditions. They also discovered that the hormone rises to even higher levels during pregnancy when the decidua is formed.

Expression of the Vitamin D Receptor in endometrial stromal cells and early pregnancy decidual cells, as evaluated by the molecular technique, Western blot.

A molecular technique called Western blot analysis showed a 40% increase in the expression of 1-OHase (which correlates with 1,25-D production) in the early pregnant decidua versus the percentage of 1,25-D created in the endometrium under normal conditions that lead to menstruation. The team confirmed these results by using another molecular technique called immunohistochemistry.

In order to confirm that not just 1,25-D, but also the VDR is found in the endometrium, the Italian team used Western blot analysis to look for the presence of nuclear receptor VDR protein. The protein was identified in both proliferate and secretory cells of the endometrium as well as in the decidua. The team confirmed their results by using a rat antibody to the human VDR that, as expected, reacted with both endometrial and decidual samples.

The team also tested whether the endometrium is a site where 25-D – the secosteroid precursor form of vitamin D – can be energetically converted to 1,25-D (the active form of the substance). The team found that the endometrium does indeed “represent a site of local conversion from the precursor to the active form” of vitamin D, and that levels of 1,25-D produced in this manner were similar to those detected in other areas of the body except for the kidneys, where conversion occurs at an even greater rate.

Cellular localization of 1-OHase in the human cycling endometrium and early pregnant decidua as evaluated by immunohistochemistry.

The functional consequences of 1,25-D production and the presence of the VDR in the endometrium were tested by evaluating the expression level of two genes that are transcribed when the VDR is activated – CYP24 and osteopontin. Levels of the genetic material that make up these genes were negligible or very low in unstimulated endometrial or decidual cells (cells that had no 1,25-D). However a “significant and strong increase” was observed in the expression of both genes after 1,25-D was added to the cells. In endometrial cells transcription levels of CYP24 went up to about 2000-fold after about a 1000nM concentration of 1,25 was added; in decidual cells this increase was also very strong. This same addition of 1,25-D stimulated osteopontin expression levels by about 60–70% in both types of cell culture.

The results of the study make one thing clear: because 1,25-D and the VDR are produced at high levels in the endometrium, the substances are over-expressed in women. Why might this be?

Truth be told, nobody knows why the VDR is over-expressed in the endometrium. One possible explanation is that since 1,25-D is the vitamin D metabolite that activates the VDR, it could be that early in human evolution, women acquired the ability to produce more 1,25-D and more VDRs because interactions between the hormone and the receptor would offer them an advantage during pregnancy. Think about it. When the Vitamin D Receptor is activated, the AMPs are produced at a greater rate, causing them to become increasingly active against viral, fungal, and bacterial infection in the fetus.

Furthermore, the innate immune system is strengthened, and hundreds, possibly thousands, of genes are expressed at a prolific rate. This provides an ideal situation for women who are preparing to bear a fetus and eventually conceive a child. Both mother and child should find it easier to fend off new infectious agents encountered during the pregnancy, and genes controlled by the VDR that may affect the success of the pregnancy should work at an optimal level.

Vigano and team seem to agree, stating, “The presence of the enzyme that catalyzes the synthesis of the active form of vitamin D in cycling endometrium and its up-regulation in first trimester decidua, support the possibility that this hormone might be involved in some mechanisms of pregnancy establishment or maintenance.”

Researchers at Children’s Hospital Medical Center in Ohio published a study in Endocrinology confirming that 1,25-D and the VDR are also expressed at high quantities in the placenta. The team found that the extra levels of the hormone and its receptor stimulate the synthesis and release of human placental lactogen – a hormone that modifies the metabolic state of the mother during pregnancy to facilitate the energy supply of the fetus. This supports the hypothesis that elevated 1,25-D and VDR expression are intended to optimize success during pregnancy.

Pathogens hijack the system

But at some point in the history of man, chronic idiopathic pathogens evolved a way to take advantage of the VDR receptor – by creating ligands that block its activity.

Biomedical researcher Trevor Marshall was the first to identify a species of bacteria that creates a ligand capable of binding and blocking the activity of the VDR. After reading a paper that discusses the characteristics of a bacterial species isolated from biofilm deposits on surgically removed human prosthetic hip joints, Marshall noted that the chronic pathogen under study creates a substance – a sulfonolipid called Capnine – that is able to bind the VDR and substantially slow its activity.

A molecular model of capnine blocking the Vitamin D Receptor.

This discovery strongly suggests that other pathogens can create similar substances, each of which can potentially block the VDR and diminish the body’s ability to keep bacteria in check. “There is now proof of concept that bacterial genomes are capable of producing at least one ligand which acts as a strong VDR antagonist,” says Marshall.

One must admit that creating a ligand or other substance capable of blocking the VDR is an exceptionally logical survival mechanism for any form of pathogen. By creating one single substance to block the VDR, they can, in a knockout blow, disable the receptor that would otherwise activate numerous pathways to interfere with their ability to persist in the body – pathways that are activated to an even greater extent by the extra 1,25-D produced in the endometrium, particularly during pregnancy.

“Think about it for a minute,” says Marshall. “If you were a persistent pathogen, wouldn’t it seem a good idea to disable your host’s ability to produce the antimicrobial peptides? And if you discovered that disabling just one receptor, the VDR, would get rid of [many types of AMPs], wouldn’t you try to evolve a mechanism for doing that?”

Because blocking the VDR is such a logical survival mechanism, the idea that most, if not all, of the L-form and biofilm bacteria (collectively called the Th1 pathogens) that cause chronic disease create these substances, is not far-fetched. This suggests that, as a person acquires more and more of these bacteria, their VDRs become increasingly blocked. As the innate immune system slows, it’s much easier for new species of Th1 pathogens, that probably also create VDR blocking substances, to accumulate and enter the body – causing somewhat of a VDR-blocking snowball effect.

Has this bacterial survival mechanism turned what was intended to be a protective situation for a woman (particularly during pregnancy and menstruation) into an environment that now allows pathogens rather than humans to gain the upper hand?

If a woman has acquired a sufficient number of Th1 pathogens, the over-expression of the VDR in the endometrium could suddenly put her at a disadvantage. Since women have more VDRs, they should, in theory, be more impacted by the effects of VDR blockage – a slower innate immune system, fewer AMPs, and reduced gene transcription. “The dysfunction caused by the Th1 pathogens affect women disproportionately,” states Marshall.

Of course, some may argue that the Th1 pathogens cannot cross the placental barrier and enter the endometrium, but evidence is growing that L-form bacteria and other pathogens are able to pass through this protective membrane.

Researchers at Peking University in Beijing recently discovered that the H5N1 bird flu virus can pass through a pregnant woman’s placenta to infect her fetus. Other studies have revealed that other bacterial species such as Borrelia burgdorferi and Mycobacterium tuberculosis are also capable of crossing the placental barrier during pregnancy. If these pathogens can be passed from mother to child during gestation, then why not species of biofilm bacteria and other forms of bacteria that are capable of transforming into the L-form?

Furthermore, if bacteria are unable to infect the endometrium and the placenta, then why do many women who have hysterectomies in order to treat diseases such as cancer or endometriosis find that the procedure affords them symptomatic relief?

For example, the 1994 Maine Women’s Health Study followed approximately 800 women with similar gynecological problems – pelvic pain, urinary incontinence due to uterine prolapse, severe endometriosis, excessive menstrual bleeding, large fibroids, and painful intercourse – for around 12 months. Approximately half of the women had had a hysterectomy while the other half did not. The study found that a substantial number of those who had a hysterectomy had marked improvement in their symptoms following hysterectomy, as well as significant improvement in their overall physical and mental health one year out from their surgery. The study concluded also that, for those who had intractable gynecological problems that had not responded to non-surgical intervention, a hysterectomy was beneficial to their overall health and wellness.

Since the removal of the uterus seems so effective at alleviating Th1 symptoms (an average of 622,000 hysterectomies a year have been performed for the past decade), one can infer that in cases where women feel better after a hysterectomy, the organ was infected – again suggesting that the endometrium is not immune to the effects of L-form and biofilm bacteria.

How might this contribute to the severe cognitive decline seen among women with CFS? It’s possible that women with VDR blockage, who subsequently have a decreased number of AMPs to kill bacteria, and a slowed innate immune system, find that the Th1 pathogens can infect their brains with greater ease. This infectious model seems logical, as nearly all females with CFS report a gradual onset of their mental symptoms – correlating to a gradual increase of bacteria in the brain.

Patients on the Marshall Protocol with diseases ranging from depression to ADD, OCD, anxiety, bipolar disorder, and schizophrenia, are reporting symptomatic improvement after taking bacteriostatic antibiotics aimed at killing the Th1 pathogens. Similarly, almost every patient on the Marshall Protocol is reporting mental as well as physical immunopathology – the name given to the rise in disease symptoms that results from the cytokine and toxin release that occurs when the Th1 pathogens are killed. Symptoms of anxiety, depression, anger, numerous kinds of brain fog, and cognitive deficits are reported along with physical symptoms, confirming that the Th1 pathogens infect the brain as easily as they do the body.

L-form bacteria have also been detected on several occasions in the brains of patients with Alzheimer’s disease. Rolf Zinkernagel at the Institute of Experimental Immunology in Switzerland demonstrated that viruses are able to persist for decades in the brain, so why not other pathogens?

Since, as described by researcher Josep Casadesus in a recent BioEssays paper, every known species of bacteria is probably capable of transforming to the L-form, this means that a plethora of different species of L-form and biofilm bacteria could be causing the neurological symptoms observed in women with CFS, explaining why symptoms are so diverse and differ substantially among individuals.

Of course cognitive decline and “brain fog” are not by any means phenomena unique to CFS. The same type of cognitive deficits observed in patients with CFS are also noted in patients with other Th1 diseases such as sarcoidosis, Lyme disease, and rheumatoid arthritis. Since the basic pathogenesis of these diseases appears to be the same as that of CFS, cognitive decline in these cohorts of patients likely results from the same mechanisms observed in CFS.

PKA

VDR blockage may also directly affect the brain through a pathway that Dr. Marshall will be discussing in his own presentation at the Days of Molecular Modeling conference. This pathway involves the enzyme CYP27B1, which plays a role in the body’s one and only pathway known to produce 1,25-D.

Under conditions where the VDR is activated, this pathway works to carefully limit (through what is known as trans-repression) the amount of transcribed CYP27B1 gene, and in turn the amount of 25-D that is converted into 1,25-D.

Researchers at the University of Tokyo recently published a paper that eloquently describes this feedback pathway in detail, pointing out other molecules involved in the process of limiting the production of CYP27B1. One of these molecules is Camp-dependent protein kinase A (PKA).

Eric Kandel

In his 2000 Nobel Lecture “The Molecular Biology of Memory Storage: A Dialog between Genes and Synapses”, Nobel Prize winner Eric Kandel (who happens to be the person who will be giving the opening talk at the upcoming DMM conference), describes how PKA is involved in broadening action potentials – spikes of energy that allow for communication between neurons in the brain. It also works to strengthen synapses, or specialized junctions through which the cells of the nervous system are able to signal to each other and non-neuronal cells such as those in muscles or glands. These findings provide direct evidence for the role of PKA in the formation of short-term memory.

When one molecule in a pathway is affected, other molecules in the pathway must adjust in order to accommodate new levels of the substance. In cases where high levels of VDR blockage disrupt the trans-repression element that keeps levels of CYP24B1 in a normal range, other molecules in the same pathway, such as PKA are also affected. As levels of PKA are modulated by higher than normal levels of CYP24B1, it is quite possible that PKA can become dysregulated – causing problems in communication between neurons that result in short-term memory loss and other cognitive symptoms.

“We have determined that activation of PKA is regulated by the process of VDR homeostasis in chronic immune disease, pointing towards a putative mechanism whereby immune dysfunction can directly suppress short-term memory,” states Marshall.

However, patients on the Marshall Protocol, who use pulsed, low-dose antibiotics to kill the Th1 pathogens, along with a VDR-agonist, to restore function of the VDR, are reporting not just the return of short-term memory, but also of mid-term and long-term memory. Consequently, it is very important that researchers continue to further investigate the connection between VDR blockage and other forms of cognitive decline besides those associated with short-term memory.

The nuclear receptors

As the Th1 pathogens take hold, the fact that women express more 1,25-D in the endometrium also becomes a problem. As the VDR becomes increasingly blocked, the receptor slows transcription of the gene for CYP24A1- an enzyme that inactivates 1,25-D. “[The production of CYP24A1] is the best documented of the feedback control systems used by the body to limit the concentration of 1,25-D to just that amount needed for proper transcription and activation of the VDR,” states Marshall.

The feedback pathways that control vitamin D metabolism. Graphic by Janet Foutin, taken from a paper by Trevor Marshall

But with a diminishing level of CYP24A1 to keep the body’s level of 1,25-D in check, the level of 1,25-D in patients with VDR blockage starts to rise. Unfortunately, when 1,25-D reaches a certain threshold, it binds many of the body’s other nuclear receptors, displacing the metabolites that are meant to be in the receptors under normal conditions. The receptors affected by 1,25-D include the glucocorticoid receptor, and the alpha and beta thyroid receptors, the adrenal receptors, and the progesterone receptors.

This means that when 1,25-D is high, it competitively displaces cortisol, T3, and other metabolites from their target nuclear receptors. Indeed, in the book Vitamin D: New Research, researcher Joyce Waterhouse PhD and team describe how patients with high levels of 1,25-D do indeed tend to suffer from hormonal abnormalities.

Furthermore, since each of these nuclear receptors transcribes various families of antimicrobial peptides, the displacement of their normal metabolites by 1,25-D causes a decrease in AMP production, generating an immunosuppressive effect (the body’s ability to kill bacteria is slowed without the help of the AMPs).

By “different families of antimicrobial peptides” I mean that there are many different types of AMPs. Although all AMPs are natural antibiotics produced by the body, each family of these peptides works to kill bacteria in different ways, and in different areas of the body.

In a recent article published in BMC Bioinformatics, a team of researchers (who are on the cutting edge of studying the role of the nuclear receptors in the transcription of different families of antimicrobial peptides) found that the glucocorticoid receptor, the androgen receptor, and the Vitamin D Receptor, seem to be in control of 20, 17 and 16 families respectively, out of 22 analyzed.

Excessive levels of 1,25-D affect the progression of chronic disease in both women and men, as 1,25-D is produced in other tissues of the body, including cells of the skin known as keratinocytes, intestinal cells, and in macrophages (macrophage-like differentiated THP-1 cells.) But since the substance is over-expressed in the endometrium, women are again disproportionately susceptible to the immunosuppression that takes place when the hormone displaces ligands from the nuclear receptors, causing a decrease in the production of so many different families of AMPs. Once again, this immunosuppression likely makes it easier for the Th1 pathogens to infect the brain, where they can cause a host of neurological symptoms.

On a similar note, researchers at Tampere University Hospital in Finland have found that several of the nuclear receptors are expressed at different levels throughout the menstrual cycle – for example the androgen receptor, the estrogen receptors, and the progesterone receptor are expressed more abundantly during the proliferative phase of the endometrium than in the secretory phase of the endometrium.

Since the expression of these receptors waxes and wanes during the menstrual cycle, even in healthy women, the activity of the AMPs that they transcribe may fluctuate over the course of a month – allowing for periods when some women may be less able to kill invading pathogens. While men aren’t affected by this surging and waning, it could be part of the reason why women appear to pick up the Th1 pathogens that cause CFS and the neurological symptoms associated with the disease at a greater rate then men.

It could also be hypothesized that women tend to acquire the Th1 pathogens that cause cognitive dysfunction more easily than men because they don’t produce as much testosterone as their male counterparts. Although on average women are more sensitive to testosterone, an adult human male body produces about forty to sixty times more testosterone than an adult female body.

Since males produce more testosterone, the hormone should activate its target nuclear receptor, the androgen receptor, to a greater extent in men than in women. Since the androgen receptor controls 20 families of antimicrobial peptides, this could mean that men produce many of these natural antibiotics at a greater rate than women – giving them an advantage when it comes to fending off infection and targeting the Th1 pathogens.

Then again, the case history of a Marshall Protocol patient suggests that the progesterone receptor may also transcribe antimicrobial peptides – albeit possibly not in the same high quantities as the androgen receptor.

The possibility that the progesterone receptor may also transcribe antimicrobial peptides is supported by the case of Jane T, an MP patient who suffers from a great number of Th1 conditions. One of the symptoms that results from her immunopathology is endometrial bleeding.

A few months ago, Jane’s doctor reported that, after being given a prescription for supplemental synthetic progesterone, her bleeding became stronger and more severe.

Could it be that upon taking the extra progesterone, her progesterone receptors stimulated the production of AMPs? If this were the case, the AMPs might have facilitated her ability to kill more of the bacteria causing the bleeding, leading to a rise in immunopathology in the area. This hypothesis is supported by the fact that her bleeding was reduced when her progesterone dose was cut in half.

Interestingly, the extra synthetic progesterone did not just affect the level of immunopathology in her endometrium. Her symptoms of obsessive-compulsive disorder increased tremendously after her initial dose of high progesterone and also decreased when the progesterone dose was lowered.

This suggests that if AMPs are produced by the progesterone receptor, they are also able to cause an increase in the death of bacteria in the brain. This case history not only sheds light on how intricately different body systems are connected and how easy it is to disrupt the body’s delicate feedback pathways, but also calls for more research into the actions of the nuclear receptors and the AMPs.

Pregnancy

Unfortunately, because of the fact that 1,25-D levels rise to their highest point during pregnancy, the hormone’s ability to cause immunosuppresion by affecting the nuclear receptors is quite prevalent during this time. The subsequent ease at which the Th1 pathogens are able to spread, thanks to the drop in AMP production, may account for part of the reason why many women with CFS often find that occasionally during pregnancy, and almost always after giving birth, they struggle with an increase in cognitive and other symptoms.

According to New York University gynecologist Frederick R. Jelovsek MD, symptoms in CFS and fibromyalgia tend to become worse during the third trimester of pregnancy and during the postpartum period, when women with CFS often report worsening of pain and other symptoms. A 1998 New England Journal of Medicine article also found that in women with multiple sclerosis (a Th1 disease similar to CFS), rates of relapse tend to increase during the first three months postpartum.

However, the majority of women with CFS feel better during pregnancy (at least during the first two trimesters) and report that their disease symptoms seem to improve. Such women are reaping the palliation derived from the decrease in bacterial die-off that occurs when less of the antibmicrobial peptides target the Th1 pathogens. Because less bacteria are killed, immunopathology drops, leading to fewer inflammatory symptoms. However such feelings of “wellness” are short-lived, as after giving birth, such women feel the effects of the new bacteria they have almost surely accumulated during the previous months when AMP production was particularly low.

It doesn’t help that most women are told to take prenatal vitamins that contain vitamin D, which only adds to the excess amount of the substance in the body. “Pregnancy is a time when (these days) the mother is being laced with prenatal vitamins, even though the endometrium is expressing lots of extra 1,25-D during pregnancy itself. So in mothers who start off carrying a sufficient bacterial load, the first pregnancy might well allow proliferation to a point that the subsequent pregnancies could be affected,” states Marshall.

Indeed, a recent study by researchers the University of Hong Kong found that anxiety and depression often increase during pregnancy and are highly prevalent and strongly associated with postpartum depression.

Among a consecutive sample of 357 pregnant women, Lee and colleagues found that more than half (54 percent) had anxiety and more than one third (37 percent) had signs of depression at some point during their pregnancies. Anxiety was more prevalent than depression at all stages of pregnancy.

Between 12 and 17 percent of women in the study were found to have both anxiety and depression at various stages of pregnancy, the researchers report in the medical journal Obstetrics and Gynecology. “Both antenatal anxiety and antenatal depression were found to be more prevalent and severe in the first and third trimesters,” Lee told Reuters Health. Anxiety and depression levels decreased from early to mid-pregnancy, but increased again late in pregnancy.

Since the mechanisms involved in pregnancy are incredibly complex and involve myriad changes – including the production of endorphins, cortisol, and many hormones – the rise in cognitive symptoms in women with CFS cannot be attributed solely to elevated 1,25-D. Yet, it certainly seems to be part of the puzzle.

The cognitive decline seen in women with CFS is serious and must be treated by killing the Th1 pathogens in the brain

While this paper probably raises more questions than it answers, several things are certain. The VDR is at the heart of chronic disease and it is doubtful that the overexpression of the VDR in the endometrium and the tendency of women with Th1 disease to suffer from a greater degree of cognitive dysfunction is simply due to chance.

Furthermore, the cognitive symptoms observed in women with CFS are incredibly debilitating and can only be reversed by a treatment such as the Marshall Protocol that targets the Th1 pathogens in the brain. This means that treatments such as cognitive behavioral therapy, which fail to address the root cause of cognitive symptoms, cannot be used to effectively treat cognitive decline in CFS.

A recent pilot study (Koolhaas, et al., 2008, Netherlands) reported that only 2% of CFS patients are “cured” by cognitive behavioral therapy (CBT), while the greatest share (38%) are actually adversely affected – most reporting substantial deterioration. The study proved to be a stark contrast to claims of psychiatrists and the Dutch Health Council that 70% of CFS patients improve after CBT. Previous studies have also ignored or denied the negative affects of CBT on ME/CFS patients. The pilot study, recently published in the Dutch medical magazine, Medisch Contact, concludes that the previously reported claims of 70% improvement in ME/CFS patients receiving CBT are vastly overstated and misleading.

In contrast, today, after a little over two years on the Marshall Protocol, Alayne feels that her cognitive function is a “gazillion times better.” According to Alayne, her improvements thus far have been absolutely stunning and very obvious.

“On the MP, my brain has been steadily healing over the past 26 months. My parents (academics) see me every 6 months or so and are able to describe the changes for me, which is great,” states Alayne. “I can read books again, although if they’re too intense or convoluted, it takes me time to understand them fully. My reasoning abilities are FAR improved as well, my math skills have returned (although I’m not sure I could teach it now), word recall is FAR better and I find myself at times uttering words I haven’t used for years.”

Alayne finds she can also spell much better again, and despite the occasional dyslexic moment, she no longer has to spell words phonetically.

She’s also able to understand and grasp new concepts far more easily, plus remember them and old ones she never really understood. “My ability to learn new software (that I couldn’t possibly do last summer), has suddenly opened up,” explains Alayne. “I was able to learn three new complicated programs within a few days last fall – ones that had completely stumped me a few months prior.”

Alayne’s level of motivation has increased greatly, up from levels of zero before the MP. “I set myself a schedule or list of ‘things to do’ and actually get them accomplished,” she states. “This is a big change. I still have some difficulties following through with some ‘things’ or projects on a timely basis, but all in all, it’s a lot better.”

In fact, Alayne is now starting a part-time job that will require her to do some freelance work that will stem from her own motivation. She’s also joined another writing group and is taking one of their courses. Since she can now remember numbers and percentages, she’s also able to do small business contracts for other people again.

“Finally, I think I’m more fun to be with,” confesses Alayne. “I’m more social and I’m eager to give feedback during conversations in my classes. I haven’t felt this way for so long.”

“We have seen no sign that the brain doesn’t heal,” says Marshall, who created the Protocol. “The adults recover all their lost faculties as they heal on the MP, and the several children on the MP, who have had a variety of difficulties, also are recovering fully. So our data (at this point) shows that the body heals as bacteria are killed and immune function is restored. All of the body. Including the brain.”

In order to emphasize the severity of cognitive dysfunction experienced by women with CFS, I leave you with the following reports from women who are using the Marshall Protocol to treat their CFS and the cognitive issues that accompany the disease. Happily, these women and others on the Marshall Protocol are experiencing strong immunopathology in the brain and some are at the point where symptoms are beginning to disappear. Complete recovery is expected once all the Th1 pathogens are targeted – a process that takes up to 3-5 years.

Jane and her cat Muffy

When did you start to get sick?

During my teenage years but it took another twenty years or so before I was to become chronically ill and debilitated.

Describe the progression of your disease

While I was at high school I had odd bouts of ill health including chronic tonsillitis and sinusitis. In 1979, while at university, I suffered an episode of sudden fatigue and paralysis in both legs which disabled me for about three weeks. I was not seen by a specialist and it was concluded that I was suffering from “hysteria.”

I was generally healthy until the early 90s when for no apparent reason I began to suffer periods of intermittent fatigue, difficulty in articulating myself, and a collection of seemingly unconnected and disparate symptoms like mild asthma, abdominal pain, weight loss, amenorrhea, malaise, and dizziness. I had an absorbing and challenging professional job, but found it increasingly difficult to perform my work. During my first pregnancy most of my symptoms surprisingly resolved and I thought I had recovered. After a severe chest infection in 1993 the intermittent fatigue became unrelenting. I resigned from my job and did part-time pro-bono work while awaiting the birth of my second child. To my dismay, I had to give even that work up when I found myself completely out of breath just walking to the station.

My symptoms improved somewhat again during my second pregnancy but I began to feel very ill indeed post partum. I developed a host of new symptoms – severe photosensitivity, compression-like headaches, tinnitus, changes in proprioreception, blackouts, hair loss, mild fever, night sweats, anxiety, edema, abdominal pain and discomfort, and, swollen lymph nodes in the neck. In 1997, I decided to consult a general hospital and an ultrasound scan revealed enlarged abdominal lymph nodes. Sarcoidosis was diagnosed on the basis of a cervical lymph node biopsy and confirmed via chest X-ray, BAL (Bronchoalveolar lavage), lung biopsies and a thoracic CT scan. Because my Angiotensin Converting Enzyme assay (commonly used as a marker of Sarcoid inflammation) was only slightly above “normal” and I did not have overt organ damage, the pulmonologist whose care I was under decided to take a “wait and see” approach.

Determined to try and preserve as much function as possible, I walked everywhere but over the next couple of years became increasingly short of breath, the fatigue grew even more profound, and swollen lymph nodes and inflamed joints kept me in chronic low grade pain. Sitting crippled by fatigue in an armchair late in the afternoon while my infant children ran riot around me, I would often wonder why I was not out sailing the world single-handed or climbing mountains like the anecdotal super-patients of the sarcoidosis specialist’s home pages.

During 1999 my headache became more prominent; I developed problems with my sense of balance and position and experienced loss of motor function and peripheral sensation in my arms and legs. I first noticed this in my hands which became very weak and clumsy. I dropped and broke many things. Eventually my fingers became too weak to even operate an ATM key pad. I lost my opposable thumbs so could not do simple things like get change out of my purse.

My legs became leaden and clumsy and I began to trip over my feet. Myasthenia and spasticity obliged me to use elbow crutches or a cane to walk most of the time. To explain how this feels to someone who has not experienced it, imagine having both legs in plaster casts to the thighs with one’s knees cast at 140 degrees. Life and my legs were a drag.

Top: The effects of ptosis and facial palsy – Jane at her worst.
Bottom: What Jane looked like without the palsy. She gets some palsy symptoms when very tired. Rings under her eyes come back when she takes one of the phase III antibiotics, although the rings are getting lighter as time goes by.

Later in 1999 I was admitted to hospital with severe muscular weakness and spasticity in all four limbs barely able to move from the neck down. MR imaging failed to reveal any gross pathology but a diagnosis of sarcoid inflammation of the spinal cord was made via clinical examination. I spent a total of five weeks in hospital, but worse still was being separated from my children for nearly three months as they had to be sent back to New Zealand. I declined methylprednisolone pulse therapy. After a poor response to 10mg/day, I agreed to 50mg/day of the oral corticosteroid prednisolone. After discharge I was kept on varying dosages of prednisolone for 3 years. Prognosis for Sarcoidosis of spinal cord at the time was that 70% patients “deteriorated”. I made arrangements with my lawyers in anticipation that I too would deteriorate, lose cognitive function, and be unlikely to live to see my children go to high school.

Short term memory problems and language difficulties, particularly with Japanese – which is a language I acquired as an adult – made life unbearable. I struggled to make myself understood at the most elementary level and would be misunderstood or treated like a child because I was unable to articulate my thoughts or feelings spontaneously. This was so humiliating that I began to consciously avoid interacting with people. I was completely overwhelmed trying to look after two young children and constantly anxious and very short tempered. Varying doses of the oral steroids left me disconnected and confused. I would do things like turn up at the supermarket counter with insufficient money in my purse, make terrible mistakes in ordering things and was forever losing important documents. Opportune infections caused a continuum of relapses that I never fully recovered from. I lived one day at a time not knowing whether when I got out of bed in the morning I would be able to walk or use my arms.

It was impossible to commit to anything more than a few hours ahead. Central Tokyo, with its aggressive traffic and poor infrastructure, was a nightmare for a disabled person. I spent most of the day asleep but no matter how much I slept it never relieved the fatigue. As my deterioration was slow and subtle those around me didn’t really notice it. It was only when I went back to New Zealand and my mother gasped when she met me at the airport that I realized how much I had changed.

Spasticity in Jane’s hand. Jane’s comment: “At a glance my hand looks normal, but if you try to actually mimick the position and angles of my fingers you will find yourself with a very distorted hand, Now that my muscles are only slightly hyper-reflexive I am no longer able to recreate the observed distortion. My feet were very spastic too at times, but I don’t have a photograph.”

For three years I half lived through a nightmare roller coaster of exacerbations and short lived partial remissions. Every step I made was a conscious effort and it seemed that all my concentration and energy went into fighting intransigent muscles. The side effects of prednisolone were horrible but every attempt to wean from it failed. I was hirsute, bloated, disconnected, and somewhere between ornery and psychotic most of the time. Ever more crippled by fatigue and cognitive dysfunction I withdrew completely and seldom left the house. The toll on my family was immense. It was as if I became the insect of Kafka’s metamorphosis.

What are your symptoms like now?

I seldom think about them.

My spinal cord inflammation has resolved to the extent that I can take tennis coaching twice a week. I have residual spasticity but it is barely discernable except to the trained eye. This is good evidence I believe, of the ability of the CNS to heal. Despite being less supple I feel as if I can run and hit the ball way better and stronger than I did fifteen years ago. I concede though that this may be related in part to having replaced my wooden racquet with a state-of-the art carbon fibre one! The aerobic exercise seems to improve my energy levels and rather than causing me to become fatigued upon exertion; I feel better for it – something that would have been unimaginable even a couple of years ago. Recently I was also quite astonished when someone remarked on the muscle tone in my arms.

Last February I took my open water scuba divers license again after a gap of 20 years and this past New Year’s Day had the time of my life sailing a Laser.

I have rejoined the world cognitively and socially. I am able to read and write again. Once a month I attend a group to read Shakespeare which has been a lot of fun. Last year I surprised a professional association of which I had been an inaugural member in the early 1990s by rejoining after 12 years. Although I did post graduate legal studies in Japanese, disuse of the language during my illness completely eroded my confidence in using it. Recently, I gained the courage to go back to language school for a stringent refresher course. This has enabled me to begin writing in Japanese and feel comfortable about interacting with people again.

I need to be a little careful about conserving my energy as I still get a little tired after taking my medication. Sometimes a recrudescence of symptoms in response to treatment will make me feel unwell for a day or so but these are nothing like the massive IP episodes of the early days. I am hopeful that they will soon resolve and I shall be able to take on professional commitments again.

Jane has now resumed her tennis lessons.

What percent recovered would you say you are?

That is a difficult question. Like everybody else my age, I would like to be a 20 year old again. As there are few precedents for a full recovery from chronic inflammatory disease, I am really having to define my own clinical endpoints. My symptoms fluctuate between 75% and 95% of normal (as compared to between 25% and 75% for the preceding 9 years). My neurological deficits are minimal and it is over a year since I have needed to use a walking aid for any reason. That is a huge milestone for me. I can run to tennis in the mornings, do a solid hour and half coaching then walk back. My bloodwork is very good now barring a couple of anomalies that indicate residual but resolving infection. ACE is down to 15.5 U/l from a peak of 35.6 U/l. Chest x-ray is normal. Lung function tests are completely normal (% predicted: VC140%; FVC141%; FEV1.0 124%;DLCO 108%) with room for further improvement. ECG which showed an ST depression prior to ARB therapy is now normal other than a slight shortening of the PR interval; I no longer suffer from heat failure symptoms (orthopnea, syncope, lightheadedness, exercise intolerance) or arrhythmia. Myasthenia as evidenced by a muscle waning decrement of 30% under Repetitive Nerve Stimulation has resolved. Lateral L2-L4 BMD (bone mineral density) has gone up from a T score of -2.47 (09/00) to -1.09 (04/07) and Z score from -2.11(09/00) to -0.23 (04/07) which I think is pretty good given that the 2007 tests were done before I began high impact sports again. For the first time in my life, I no longer have any nasal congestion and an irritating nasal polyp I had for 15 years has disappeared. Headaches are a thing of the past. I still get the odd bout of fatigue but it is seldom for long. I am generally able to articulate myself in both English and Japanese, I enjoy reading and my short term memory has improved significantly. Most fascinatingly and delightfully I am gradually regaining the memories of people and events from the ten or so years prior to CNS involvement that appeared to have been lost.

In time, I hope to be able to proclaim of sarcoidosis, as did fellow New Zealander, the late Sir Edmund Hillary after conquering Mt. Everest… that I have “knocked the bastard off!”

ACE (Angiotensin Converting Enzyme) is a marker that reflects the severity of inflammatory diseases such as sarcoidosis. In Jane’s case, you can see her ACE was high when starting the treatment and also flared during bacterial killing, but in the end has fallen and continues to fall.

What was your immunopathology like? Was it very strong or easy to control? How did you manage it?

My immunopathology (bacterial die-off reaction) was severe at times and hard to manage psychologically. It typically involved sudden severe weakness and loss of motor function, sometimes in a single limb (I once had to finish a bowl of noodles using chopsticks in my left hand!), in opposing limbs and occasionally in all four limbs rendering me bed-bound until it subsided.

This was particularly so while the MP antibiotic regimen was being developed. There were no set dosages then and the necessity for maintaining sub-inhibitory concentrations on a pulsed schedule was not yet fully understood. I moreover did not have the benefit of Olmesartan in the early stages (it was not yet available in Japan) so had a very difficult time managing the immunopathology (IP). However, after I began suffering from symptoms indicating cardiac inflammation, I was prescribed an ARB called Valsartan. To my amazement, around five days after starting it, the symptoms all but resolved. Not quite believing that Valsartan could have had such an effect, I decided to take a self-appointed “holiday” from the drug a couple of weeks later. Ten hours after missing my dose, the symptoms returned in full force. I resumed the Valsartan and to my relief the symptoms began to resolve some hours later. This convinced me of the phenomenal power of ARBs to alleviate inflammation and without any side effects. I never looked back. Soon after, I was finally able to switch from Valsartan to Benicar. I noticed even more improvement once on Benicar and what are now the standard MP antibiotics.

Top: After taking a break from the MP in May of 2004, Jane developed edema (swelling) in her foot. Her eyes, face, belly, and hands all swelled at the time.
Bottom: The edema went away six days after she resumed taking Benicar.

For the first year and a half on the MP however, I had quite a rocky time. I experienced an endless and incoherent parade of old and new symptoms and what seemed like no real change. A small increase in inflammation in the central nervous system is capable of deranging the function in very different areas of the body so even when transient it can be quite disconcerting. But about nine months into MP Phase II, I suddenly began to notice slight improvements in function and from there on my IP became more stable and my gains sustained.

To date however, no matter how severe my IP, I have been able to manage it by adjusting the timing, amount or constitution of my antibiotic therapy and by increasing my Benicar dosing. This has necessitated some very detailed and timely advice from the MP staff and a huge dose of courage at times but it has invariably worked.

What was the hardest part about doing the MP?

Believing that I was getting better. I had never really thought of myself as “sick,” just a normally healthy person with some irritating problems that I needed to get rid of and quickly. I wanted a magic bullet which the MP is not. It takes time and you have to persevere.

How did you learn about the MP?

In 2002 I had a three-month remission following a course of an antibiotic prescribed for an opportune infection. As this was the second time I had noticed an improvement in my condition after a short course of an antibiotic, I decided to investigate whether there was any connection between my perceived remission and the etiology of sarcoidosis. I typed in “Sarcoidosis” and “remission” and found Sarcinfo.com – the precursor website to what is now the Marshall Protocol study site.

What made you decide to do the treatment?

When I received the diagnosis of sarcoidosis, my father who is a pathologist, had remarked to me that tuberculosis, leprosy, and other granulomatous diseases looked quite similar to sarcoidosis under the microscope so, it was quite conceivable that Sarcoidosis also had an infectious etiology. That insight remained my guiding light. I had already observed two brief remissions after taking antibiotics for opportune infections and was sure that there was a correlation. The role of the vitamin D receptor in chronic inflammation was a great revelation however. While in hospital, I had begun to think that the inexplicable and sometimes severe fluctuations in my symptoms might be hormonal. I even bought a monograph about hormones, however Vitamin D was mentioned only in relation to its role in calcium metabolism so I didn’t make the connection. Later, when I read the Marshalls’ “Angiotensin Hypothesis,” it was like finding the missing piece to a 1000-piece jigsaw puzzle.

I had my 1-25-D/25-D ratio measured and it came out at 4:1 (normally the ratio should be around 1:1.1). Not only did I have an excess of this chemical in my body, it was a steroid hormone that was interfering with the activity of my immune system. Finally I had found a plausible explanation for many of my bizarre and often transient symptoms. My doctor was also persuaded on the basis of my D metabolite test results to prescribe the MP prototype antibiotic therapy on the condition that I persevere with any antibiotic chosen for a minimum of three months.

What was it like to be one of the first people to start the MP?

I felt like an intrepid explorer. I was strongly convinced of the science behind the MP and always kept in mind Pasteur’s dilemma when he decided to treat Joseph Meister for rabies. I had two young children who needed a mother. There was a small chance that the medications might adversely affect me, however the alternative was a half of a life on steroids and a cornucopia of toxic palliative drugs that would do nothing to alter the course of the disease.

Although I had little or no access to information in Japan, the support I received through Sarcinfo and the extraordinary generosity and vision of the American people in making the website PubMed freely available online enabled me to become the arbiter of my own destiny. I was able to make informed choices and to participate in an international clinical trial through the Marshall Protocol study site that I would never otherwise have been considered for. I was more than happy to participate in this experiment, if, as a result, even one person could be spared the misery I had endured.

As the protocol developed and positive responses to the therapy filtered in however, the magnitude of Trevor Marshall’s vision became apparent. Not just a few sarcoidosis patients but many, many patients suffering from a wide range of chronic diseases stood to benefit from the therapy. The feeling was one of exhilaration.

Describe your experience with light. Were you very sensitive at first? How much light can you tolerate now?

During my early days on the MP, I was extremely sensitive to light and had frequent transient black-outs while working under the fluorescent lighting of my kitchen bench. When the blackouts began to occur while I was driving, I stopped driving. Flickering light from any source would make me anxious and irritable and I always wore sunglasses outside because I found looking into sunlight so painful.

Interestingly, I always felt very peaceful when wearing goggles while skiing and it wasn’t until I first bought a pair of NoIR glasses that I understood why. The relief they provided, and still provide is immense. I have largely lost my photosensitivity but still wear the glasses outside as a matter of habit and precaution. Today patients on the MP are required to block light with NoIR glasses until photosensitivity subsides.

How does your doctor feel about your progress?

My physicians have been very supportive. The prognosis for sarcoidosis of the central nervous system is not very good so I would say that my progress has been greeted with “cautious optimism.” One has to remember that neurologists are not particularly used to seeing patients go from crutches to the tennis court.

What advice do you have for new patients on the MP or current patients?

Think Big!

Be knowledgeable and courageous about beginning the MP. My life would have been very different had the MP been available ten years ago. I “lost” what should have been the best ten years of my life.

Read. Understand your clinical condition and the science underpinning the MP as best you can so that you can understand how a temporary exacerbation of symptoms appearing as IP might affect you. Keep good records. I keep two Excel databases:

1. a daily “Drugs vs Symptoms daily monitor”

2. blood test results which I graph to show trends

I keep copies of all diagnostic tests undergone and (no matter how unpleasant this may seem) get people to take digital photographs and occasionally videos of my symptoms.

What lies ahead?

To return to my professional work very soon I hope.

To be able to follow my dreams again – “Last seen sailing an RS800”?

Not to need another doctor’s appointment for the next 35 years.

Interested in doing the Marshall Protocol yourself? Visit curemyth1.org and your questions will be answered free of charge by experienced patient advocates that volunteer for the non-profit organization that runs the treatment. (Th1 is a name currently given to diseases caused by L-form bacteria, hence the name cure my Th1)

“This drug makes women stupid,” Orli Etingin, vice chairman of medicine at NewYork-Presbyterian Hospital, declared at a recent luncheon discussion sponsored by Project A.L.S. to raise awareness of gender issues and the brain. Dr. Etingin, who is also founder and director of the Iris Cantor Women’s Health Center in New York, told those present about a typical patient in her 40s, who after taking Lipitor was unable to concentrate or recall words. Tests found nothing amiss, but when the woman stopped taking Lipitor, the symptoms vanished. When she resumed taking Lipitor, they returned.

“I’ve seen this in maybe two dozen patients,” Dr. Etingin said later, adding that they did better on other statins. “This is just observational, of course. We really need more studies, particularly on cognitive effects and women.”

Gayatri Devi, an associate professor of neurology and psychiatry at New York University School of Medicine, says she’s seen at least six patients whose memory problems were traceable to statins in 12 years of practice. “The changes started to occur within six weeks of starting the statin, and the cognitive abilities returned very quickly when they went off,” says Dr. Devi. “It’s just a handful of patients, but for them, it made a huge difference.”

Researchers at the University of California at San Diego are nearing completion of a randomized controlled trial examining the effects of statins on thinking, mood, behavior, and quality of life. As part of a separate project the team is also collecting anecdotal experiences of patients, good and bad, on statins. They’ve found that in about 5000 people to date, memory problems are the second most common side effect, after muscle aches.

“We have some compelling cases,” says Beatrice Golomb, the study’s lead researcher. One case is that of 69-year-old Jane Brunzie, a San Diego woman who after taking a statin became so forgetful that her daughter sought to put her under care for Alzheimer’s and refused to let her babysit for her 9-year-old granddaughter. Then Brunzie stopped taking the statin. “Literally, within eight days, I was back to normal — it was that dramatic,” says Brunzie.

Doctors put her on different statins three more times. “They’d say, ‘Here, try these samples.’ Doctors don’t want to give up on it,” she says. “Within a few days of starting another one, I’d start losing my words again,” says Mrs. Brunzie, who has gone back to volunteering at the local elementary school she loves.

“I feel very blessed — I got about 99% of my memory back,” she adds. “But I worry about people like me who are starting to lose their words who may think they have just normal aging and it may not be.”

There’s no doubt that some women who take Lipitor, also called atorvastatin, are experiencing increased mental problems. But is their loss of cognitive function an unexplainable side effect of the drug, or is something else going on?

That something else may very well be immunopathology – or the immune system’s response to bacterial death. Women who are prescribed statins are almost certainly infected with L-form bacteria, as the pathogens and other biofilm bacteria (collectively called the Th1 pathogens) are responsible for causing the inflammation that leads to high cholesterol.

As patient reports from the Marshall Protocol site confirm, the Th1 pathogens seldom infect only one area of the body, and everyone in the population acquires them as they age. This means that many women prescribed statins for high cholesterol very likely have these bacteria in their brains as well.

Aside from mild episodes of brain fog or memory loss, most women on statins are probably unaware of the that fact their brains may harbor Th1 pathogens, largely because it’s not until these bacteria are killed that the host becomes acutely aware of their presence.

When the immune system targets the Th1 pathogens, it releases a host of inflammatory molecules in response to their death, which along with the toxins released by the bacteria as they die, and the debri from the cell they once inhabited, cause a rise in symptoms in the area in which the bacteria are been killed (immunopathology).

Interestingly, biomedical researcher Trevor Marshall’s recent molecular modeling research has made it abundantly clear that while statins do lower cholesterol, their main actions on the body come not from their cholesterol lowering properties but from the fact that they bind the nuclear receptors – a class of receptors intrically connected to the activity of the innate immune system. These receptors include the Vitamin D Receptor, the glucocorticoid receptor, and the alpha and beta thyroid receptors.

These are the same receptors activated by Benicar – the ARB medication used by patients on the Marshall Protocol; the medication that activates and enables the innate immune system. In fact, drugs such as Benicar that bind and activate the nuclear receptors can be so effective at turning on the innate immune system that they enable some people to kill the Th1 pathogens even without the help of antibiotics.

Despite the fact that Lipitor doesn’t bind the VDR directly, it still affects, and could very likely activate, the immune system because it binds both the glucocorticoid and thyroid receptors with a very high affinity in both cases. Could this mean that those women who experience a rise in cognitive symptoms from Lipitor are simply feeling the effects of bacterial die-off in the brain as the statin allows their immune system to target pathogens in that area more effectively?

Brain fog, memory loss, inability to process and retain information, loss of problem solving skills, and significant drops in other areas of cognitive function are certainly observed among women who begin to kill bacteria on the Marshall Protocol.

If this is the case, then those women to experience cognitive side effects from Lipitor would be best off starting the Marshall Protocol – using Benicar and the MP antibiotics to fully eliminate Th1 pathogens in the brain. Of course, until the ability of statins to activate the nuclear receptors and the presence of the Th1 pathogens is accepted by mainstream medicine, women like Jean Brunzie will remain perplexed as to how a simple cholesterol lowering medication could so profoundly effect their mood, memory, and ability to think.

The results of this study jive with the work of researchers such as Dr. Trevor Marshall who, while investigating the manner in which L-form bacteria affect people as age, have found that few, if any, people are spared from the actions of these pathogens as they reach their later years.

L-form bacteria are hardy survivors – they cannot be killed by pasteurization or chlorination, nor can they be eliminated by filtering processes or tecniques that purify injectible medicines. They are even found in dry soil. Not to mention that fact that the ubiquitous use of corticosteroid medications, and supplements such as vitamin D (which is itself a corticosteroid), has reduced the immune function of most of the population to the point where L-form bacteria can survive and spread with ease.

Once in the body, these pathogens create ligands which dysregulate the Vitamin D Receptor – slowing the activity of the innate immune system and the antimicrobial peptides, causing the host to further succumb to the actions of these cell-wall-less forms.

Some people eventually fall ill with recognized mental diseases such as Alzheimers and dementia – diseases which have recently been linked to L-form bacteria. But in the majority of cases, the cognitive decline seen amongst the elderly is simply considered a “normal” part of the aging process. This begs the question – are these people suffering needlessly, and if so, do they have signs of brain damage which indicate that they too could benefit from therapy aimed at killing L-form bacteria?

Indeed, this seems to be the case. The Rush team, under the direction of Dr. Julie A. Schneider, evaluated the spectrum of abnormalities found in the brains of 141 older adults, with and without clinically evident dementia. They found that at the time of death, only 20 persons (14.2 percent) were free of brain disease.

The diseases most commonly detected were Alzheimer’s disease pathology and cerebral infarcts (strokes), followed by Alzheimer’s disease and Lewy body disease.

The researchers found that the only way to distinguish persons with dementia (i.e., memory and other cognitive impairments) from “healthy” subjects was the fact that dementia patients tended to have more than one type of pathology in their brain causing impairment, whereas “healthy” subjects tended to have signs of only one disease.

However older persons without dementia frequently had brain disease, most commonly Alzheimer’s-like disease, but also multiple other abnormalities. Having more than one disease in the brain significantly increased the likelihood that symptoms of dementia will be present.

“Older persons can often handle one pathology in their brain, but the burden of more than one pathology may tip them over the threshold of clinical dementia,” argues Schneider.

In the end, the results show that nearly the entire population suffers from brain damage as they age, including people deemed as “normal” by mainstream medicine. It’s proof positive that the vast majority population is infected with L-form bacteria and that as the Marshall Protocol gains acceptance, and L-form bacteria are killed, mental decline may no longer become a hallmark of the aging process.

Payne found that subjects who consumed vitamin D were markedly more likely to have a higher total volume of brain lesions.

The research team was led by Dr. Martha E. Payne, an assistant professor in the department of psychiatry and behavioral sciences with the Neuropsychiatric Imaging Research Laboratory at Duke. Payne reported her findings at the 2007 Experimental Biology Conference in Washington D.C. Her presentation, which took place on May 1, is part of the scientific program of the American Society for Nutrition.

“This is one of the first studies to examine the relationship between diet and brain lesions,” said Payne. “Our finding of a relationship between brain lesions and consumption of both calcium and vitamin D raises the question about a possible downside to high intakes of these nutrients.”

The team examined magnetic resonance imaging (MRI) scans from 232 men and women (79 men, 153 women) between the ages of 60 and 86 (average age 71). All the subjects had at least some brain lesions of varying sizes, including the extremely miniscule ones often seen in even healthy older persons, but those who reported consuming more calcium and vitamin D were markedly more likely to have a higher total volume of brain lesions as measured by MRI scans.

Even after controlling for other factors known to be related to brain legions such as age, hypertension, and other medical conditions, the strong relationship between total lesion volume and high intake of calcium and vitamin D remained. Since the calcium/vitamin D research was part of a longitudinal study of late-life depression, almost half the subjects had been diagnosed with depression. However, the presence or absence of depression also did not appear to influence the relationship between vitamin D and brain lesions.

In earlier studies, Payne and team had found that individuals who consumed more high-fat dairy products had more brain lesions than those who did not follow such a diet but determined that fat intake in general was not a significant factor. However vitamin D is found in high fat dairy products, and a large number of dairy products are fortified with extra vitamin D. Hence the team’s idea to investigate the effect of vitamin D on brain lesions.

Unaware of the latest research on the immunosuppressive properties of high levels of vitamin D, the researchers hypothesized that the calcium rather than the vitamin D was the main culprit in causing the lesions. They speculated that in patients given extra calcium, the calcium might be deposited inside the blood vessels of the brain rather than the bone. According to their theory, vitamin D would accelerate the process because it is involved in regulating calcium absorption and metabolism.

In what is emerging as a new understanding of chronic disease, a much more likely explanation is that the lesions result when L-form bacteria in the brain cause the release of cytokines that damage the tissues. Sometimes the resulting inflammation damages blood vessels and promotes calcification, but it is the L-form bacteria, not the calcium that is the true culprit.

The connection between bacteria and calcification in heart disease has already been noted. Researchers at the Hospital Das Clinicas in Brazil found significantly higher concentrations of Chlamydia pneumoniae and Mycoplasma pneumoniae in calcified nodes of blood vessels throughout the body, including the heart and the aorta – causing them to suggest that “these bacteria may be associated with the development of calcification and inflammation.”

Nearly everyone acquires L-form bacteria as they age. Rolf Zinkernagel at the Institute of Experimental Immunology in Switzerland demonstrated that viruses are able to persist for decades in the brain, so why not other pathogens? It’s not surprising then, that Dr. Alan Macdonald at St. Catherine of Sienna Medical Center found evidence of L-form bacteria in the brain of patients with Alzheimer’s disease.

Elderly patients are particularly susceptible to the immunosuppressive effects of 25-D.

Researchers at the University of British Columbia in Canada have also implicated bacteria in Alzheimer’s Disease. The data obtained from patients on the Marshall Protocol study site also confirms that L-form bacteria are able to infect the tissues of the central nervous system, since patients with a wide variety of mental illnesses and types of cognitive impairment are responding to antibiotic therapy. Studies like these support the view that the elderly patients in Payne’s study had acquired substantial levels of L-form bacteria during their lifetimes.

Why would ingesting vitamin D affect the proliferation of L-form bacteria in the brain? New molecular modeling research by biomedical researcher Trevor Marshall of Autoimmunity Research Foundation has revealed that the precursor form of vitamin D – the steroid 25-D – binds and inactivates the Vitamin D Receptor (VDR), a fundamental receptor of the body that controls the activity of the innate immune system. As people consume products fortified with vitamin D or take supplements containing vitamin D, the level of 25-D rises, often to the level at which it becomes immunosuppressive. It appears that the elderly patients in Payne’s study were consuming levels of vitamin D that were sufficient to block the VDR. As their immune function decreased, the L-form bacteria in their brains were able to spread, proliferate and consequently stimulate the release of an increasing number of cytokines that damaged the tissues of the central nervous system and caused brain lesions.

Furthermore, elderly patients are particularly susceptible to the immunosuppressive effects of 25-D. Bacteria have been identified that can bind and block the VDR in a manner similar to 25-D. Since elderly patients generally have had more time to accumulate bacteria, they would tend to have a greater level of bacterial substances already blocking the VDR. Consequently, 25-D will be likely to exacerbate immunosuppression from VDR blockage already taking place. This means that even relatively low levels of vitamin D supplementation can negatively affect the activity of the immune system in elderly patients.

Certainly, then, it comes as no surprise that the researchers found that only the vitamin D, and not calcium, remained significantly positively associated with brain lesion volume. Since it was an observational study, the researchers used surveys to track how much vitamin D and calcium the subjects obtained from food and supplements. Many supplements and dairy products contain both calcium and vitamin D so a multivariate analysis was used to statistically separate the two variables.

If the calcium had been the primary problem, then the calcium should have had an independent association with the lesions in the multivariate analysis, apart from the vitamin D, and it did not. Only vitamin D had a significant correlation when the effect of calcium was removed. And this occurred even though patients were not ingesting particularly high levels of vitamin D. No patient was consuming more than 1015 IU of vitamin D and only a handful were getting more than 800 IU of vitamin D from foods and supplements combined.

Interestingly, most of the articles written by journalists about the research fail to mention this incredibly important detail, and make it sound as if the calcium was a greater culprit than the vitamin D in causing the brain lesions. Only a few articles mention that calcium was not actually associated with the brain lesions when the researchers analyzed it in the multivariate analysis.

Why is there a bias with regard to vitamin D? There are multiple explanations, among them the fact that researchers seem unable to fathom the idea that any negative effects might be caused by the cherished “sunshine vitamin.” (More info available here.)

MRI testing is used to detect brain lesions.

Not surprisingly, brain lesions are connected to a variety of diseases that are likely to be caused by L-form bacteria. A study by researchers at National Cheng Kung University in Taiwan found that brain lesions shown by MRI were associated with late life depression. Researchers at the University of California at Davis correlated brain lesions with a number of neuropsychiatric disorders, including vascular dementia and Alzheimer’s disease. A team at McLean Brain Imaging Center and Harvard Medical School found an association between brain lesions and bipolar disorder. Another study conducted by researchers at the University of Michigan followed a group of community dwelling older adults for 11 years. They found that the group with the greatest volume of brain lesions experienced an approximately two-fold increased mortality rate. Brain lesions have also been correlated with major depressive disorder with anger attacks, conduct disorder/attention deficit disorder and suicidal tendencies.

Additionally, researchers at the University of New South Wales in Australia found that brain lesion volume as shown by MRI correlated with several measures of brain atrophy. Another recent study of 51 healthy volunteers (average age 71) by the same Australian team confirmed that these lesions are typically progressive, although 8 subjects had a slight decrease in lesion volume over 3 years, indicating the potential for lesion reversal.

Consequently, there is great hope that people who develop brain lesions can reverse damage to the brain by using the Marshall Protocol – a treatment that effectively kills L-form bacteria over the course of several years. While on the treatment, patients greatly lower their intake of vitamin D.

“We have seen no sign that the brain doesn’t heal,” says Marshall, who created the protocol. “The adults recover all their lost faculties as they heal on the MP, and the several children on the MP, who have had a variety of difficulties, also are recovering fully. So our data (at this point) shows that the body heals as bacteria are killed and immune function is restored. All of the body. Including the brain.”

Of course, many doctors justify telling the elderly to supplement with vitamin D because they think it will help increase their bone mass. However, the largest meta-analysis of calcium and vitamin D trials in people over 50 found that the “addition of vitamin D supplementation was not shown to offer additional risk reduction over and above the use of calcium alone.” Similarly, a study by researchers at the Indiana University School of Medicine found that calcium supplementation (about 1300 mg) improved bone density over a four-year period, whereas vitamin D supplementation (600 IU) had no effect. In fact, the effect of calcium on bone loss was blunted in subjects with the highest levels of vitamin D, causing the team to point out the danger of over-supplementation of the elderly with vitamin D if they are on an adequate calcium intake.

One can hope then, that Payne’s study on the connection between vitamin D and brain lesions is just the beginning of more research in this area. “A longitudinal study,” Payne concludes, “is urgently needed in order to determine if calcium and vitamin D lead to vascular calcification and brain lesions in the long term.” The urgency is certainly justified considering the increasing tendency of certain researchers and supplement manufacturers to promote a greater intake of vitamin D, particularly among the elderly.

This article by Joyce Waterhouse, Ph.D. discusses additional information on brain lesions, vascular calcification, osteoporosis, vitamin D and calcium.