Abnormal sensitivity to sunlight and bright lights is known as photosensitivity and sometimes referred to as “sun flare” or photophobia. In the context of the MP, the ultimate cause of photosensitivity is the Th1 inflammatory disease process – not the treatment itself. Exposure to natural or bright artificial light in a photosensitive person can lead to flares of internal disease activity, including exacerbation of any inflammatory disease symptoms.
Photosensitivity can occur either when the skin is exposed to bright natural light or the eyes are exposed to either natural or artificial light. Photosensitivity symptoms can occur immediately after exposure or begin 1 to 3 days later, sometimes persisting 5 days or more.
Individuals who are photosensitive prior to the MP will likely become more photosensitive on the MP. Individuals who have no signs of photosensitivity may or may not become photosensitive on the MP. Individuals with limited inflammatory symptoms (suggesting early disease) are the most likely to be able to tolerate more light exposure while on the MP. There is no certain way to tell in advance precisely how photosensitive an individual will be while on the MP. Only after an individual has begun treatment can photosensitivity be assessed.
Even though the exact mechanisms by which Th1 disease leads to photosensitivity remains clouded, photosensitivity is well associated with Th1 disease. Examples of photoaggravated diseases include lupus erythematosus, erythema multiforme, atopic eczema, psoriasis, viral exanthemata, pemphigus, dermatitis herpetiformis, rosacea, and multiple sclerosis.1 2 3 Even so, the variety of MP treatable illnesses for which there is a photosensitivity component and the severity of the photosensitivity reaction is widely underestimated by the majority of clinicians and researchers. This may be due to the time window for an adverse reaction, which is often hours or days after light exposure.
The photosensitivity observed among the MP patient cohort is not due to the medications. It is part of the healing process.
If you see photos of me from the period 1987-1999, a decade before the MP, when I was taking no medication whatsoever, you will see me with those 98% Zeiss glasses, which I had to wear everywhere.
Once you start cutting the vitamin D so that your immune system can start functioning properly again, the photosensitivity sets in, and it will stay for 6-24 months, gradually decreasing as you progress on the MP.
As you recover you will get to the point where you can't see anything through those dark glasses any more.
Trevor Marshall, PhD
Note that photosensitivity occurs with sufficient frequency that it is listed as an adverse side effect for patients who take at least one form of Benicar, Benicar HCT, a form which contains thiazide, a diuretic which is contraindicated for MP patients. The reason why it is not more common is that people who take Benicar irregularly (by MP standards) have not taken it consistently enough for a full Benicar blockade to be in place.
Some people feel worse when they begin to avoid sun exposure, causing symptoms such as fatigue, dizziness, headache, photosensitivity, irritability, sleep disturbances, and brain fog. It is also common to become more sensitive to natural light after avoiding sun exposure because the resulting fluctuations in the level of 1,25-D can exacerbate symptoms even if the level of 1,25-D is relatively low. Wearing the required sunglasses may relieve symptoms by calming the neurological effects of light, but it can also make it more difficult to tolerate light without the sunglasses.
In individuals with chronic inflammatory diseases, 1,25-D is rapidly synthesized from 7-dehydrocholesterol when sunlight falls on the keratinocytes of the skin. According to the Marshall Pathogenesis, many of the keratinocytes of Th1 patients are parasitized by bacteria, they produce interferon-gamma (which is part of the bacterial defense mechanism) and TNF-alpha. These cytokines cause the cells of patients to produce much more 1,25-D in their skin than their healthy counterparts. Studies show that all 25-D produced in the skin of individuals with Th1 disease from sunlight is hydroxylated directly into 1,25-D, leaving no 25-D to be stored in fatty tissues. In healthy people, however, there will be remnant 25-D generated. Photosensitivity does not seem to be correlated with a patient's level of 25-D.
…you cannot judge your level of photosensitivity by your level of 25-D. It is far more likely that exposure of the skin to the sun will directly produce 1,25-D in a Th1 patient than 25-D. This is both because of the metabolism, as described in our paper and because an earlier in-vitro study showed just that.
Trevor Marshall, PhD
In patients who get enough natural light on their skin on a regular basis, 1,25-D can elevate high enough to become immunosuppressive and stop bacterial killing. A study of frequent tanners found that the practice has an addictive quality – an effect which, according to the Marshall Pathogenesis, is due to systematic immunosuppression of high levels of 1,25-D.4
However, most MP patients do not get enough regular continuous light exposure on their skin to offset the olmesartan (Benicar) blockade. They can, however, get a surge of natural light exposure that causes an increase in symptoms due to rapid fluctuation of hormones including 1,25-D.
The majority of sunscreens are ineffective in blocking vitamin D production or blocking sun flare symptoms in Th1 patients.
A recent study in mice cast doubt upon the skin as a major producer of 25-D, even though they it was shown that UV exposure on the skin likely does suppress the immune system through multiple pathways.5 It is possible the effect on the body is to cause the catalysis of 25-D systemically, although nobody seems quite sure of that just yet.
I find it hard to continue to cling to the pragma that the skin produces 25-D solely under the influence of UV light. The actual situation is clearly a lot more complex than this, and lines up with some members' experience that even indirect sunlight can cause them severe discomfort.
So I would caution members against any outdoors exposure which gives disquieting symptoms. Photosensitivity is eventually lost as the immune system recovers. Additionally, some of our members never really experience noticeable problems out-of-doors. Photosensitivity seems to depend on the individual's microbiota at any point in time.
Trevor Marshall, PhD
The eyes have a complete, self-contained, renin-angiotensin system (RAS) in them. They are connected directly to the brain via the optic nerve. Any type of bright light (artificial or solar) falling on the eyes causes, via the RAS, the production of a small amount of systemic 1,25-D. Whether exposure of a Th1 patient's eyes to light generates excess quantities of 1,25-D, which then enters the brain or systemic circulation, is not yet well understood.
There is no data on this, and very little we can use to try and guess at the probabilities involved. Even the circulations are somewhat in question at the moment.
It is important for folk who exhibit photosensitivity while they recover their health (which is nearly everybody) to protect their eyes fastidiously. The exact mechanism(s) remain(s) clouded, however.
Trevor Marshall, PhD
The optic nerve directly connects each eye to the brain, possibly the body's most sensitive organ. Thus, light is transmitted to the brain via the eyes. Coursing through the portion of the brain known as the amygdala are nerves connecting it to a number of important brain centers, including the neocortex and visual cortex. Many types of angiotensin receptors are known to be active in the brain. This can have the profound effect of stimulating portions of the brain to cause significant neurological symptoms.
This stimulation of the brain causes many of the neurological symptoms that are so bothersome to individuals with Th1 inflammation. Neurological symptoms include fatigue, irritability, aggressiveness, lack of concentration, brain fog, loss of memory, poor judgement, confusion, anger (Lyme rage), mood swings, anxiety, inattentiveness, poor problem-solving, fear, neurosis and even psychosis.
Decreasing the light that falls on the eyes will make the brain comparatively stable and symptom-free, thus, it will be easier to deal with the surges in immunopathology which will inevitably occur.
The first test of a patient's suitability for the MP is typically the therapeutic probe, which includes Benicar, antibiotics, and the restriction of vitamin D, of which light can catalyze the creation. The therapeutic probe offers early insight into any photosensitivity associated with the disease process, especially sub-clinical inflammation. In deciding how much light to expose themselves to while on a therapeutic probe, patients are advised to work with their physician and to err on the side of caution. Safety should be the primary concern, especially for patients with cardiac, respiratory, and neurological symptoms.
MP patients who expose themselves to light from all sources will soon know if they can tolerate light, and to what degree, based on their symptoms.
There is no typical length of time between natural light exposure and a symptom flare. Some will feel the effects within an hour or two while others may not experience an increase in symptoms for a day or longer. An MP patient's reaction to light exposure may be delayed. Before beginning the MP and avoiding light, many people do not associate this delayed reaction with their disease symptoms since daily exposure and a consistent elevated 1,25-D can mask the effect of this inflammatory process. Once one diligently begins avoiding all sources of sun and bright light, it is easier to correlate the sun or light exposure with its effect on symptoms when the exposure to sun and bright lights is sporadic.
While rare, it is important to note that some MP patients may be at high risk for an acute adverse event caused by sunlight exposure or because the innate immune system, once activated by the MP, continues to kill the bacteria. All MP patients should report adverse symptoms to their physician and understand how to manage a significant adverse event should it occur. MP patients are encouraged to report regularly on the website in order to get early help managing symptoms. A range of measures is available to dampen intolerable symptoms.
Most of the original clinical experience of the MP research team had been with individuals who were so ill they were unable to work or to tolerate even moderate outdoor activities. Others were sufficiently sick to be motivated to make accommodations in their workplace and home in order to avoid light. When they began the MP, these very symptomatic early-adopters almost always noticed a high level of photosensitivity (which resulted in an emergence of or an increase in neurological symptoms during and/or after exposure to sunlight).
Later, however, re-evaluation of reports from the enlarged MP patient cohort has led the MP research team to conclude that people who are less ill may not experience significant photosensitivity. Generally speaking, patients who are more ill and/or more photosensitive prior to beginning the MP will be more photosensitive while on the treatment. However, immunopathology is highly variable, and as puzzling as this concept may appear to some, a bad reaction to light exposure can be life-threatening.
As MP patients' vitamin D metabolism is “reset,” their sensitivity to light diminishes. This will be a gradual process. Later on in the Protocol, MP patients should be able to handle “normal” amounts of sunlight because, in the short period between maintenance doses of antibiotics, they will maintain low bacteria loads.
Photosensitivity is just that, photosensitivity, and it will gradually disappear with time. You need to keep an eye on your general immunopathology and make sure you are progressing on-track to recovery, but otherwise, when you can enjoy the outdoors again, it is a good idea to do so. A little at a time.
As one progresses through Phase 2, the risk of setback from occasional exposures becomes less and less. Eventually the risk disappears (although you will probably never want to sunbathe again). The only way to find out is to try a few “baby-steps” and see. I usually say it takes 18-24 months to get back to any sort of “normal” sensitivities, though.
Trevor Marshall, PhD
In the case of immunopathology – which is generated during the MP and a key part of the recovery process – inflammation from intracellular bacteria affects many areas of the brain, making it difficult to differentiate between neurological symptoms from light stimulation and from immunopathology. Dr. Brian Fallon's study on Lyme found from SPECT data that the main metabolic changes in the brain were in the region of the parahippocampal gyrus.6 This area is responsible for receiving sensory input from the outside world, integrating it, and projecting it onto the hippocampus, which controls memory, and the amygdala, which is in charge of fear, aggression, and mood. Negative symptoms associated with memory, fear, aggression, and mood can certainly be exacerbated by light.
There are two different and independent phenomena, which occur when one is on the MP, both of which are correlated with a temporary rapid rise in 1,25-D: photosensitivity symptoms and immunopathology. Differentiating between immunopathology and photosensitivity symptoms is very important as the former is necessary for progress on the treatment and the latter is not.
Exposure of skin (and perhaps the eyes also, as discussed above) to light does not result in immunopathology. It causes 1,25-D to go up. The rise in 1,25-D causes symptoms of hypervitaminosis-D. This may feel like immunopathology but it is a flare in disease symptoms and a hormonal shift due to elevated 1,25-D, not the result of the immune system killing bacteria. A sun flare would be similar to pre-MP inflammation.
The increase in 1,25-D due to sun exposure will increase inflammation everywhere and may not be perceived as photosensitivity but will be evident as any type of symptom, including even worsening lab test results.
I have been on the Protocol for several years now (7), and in my recent experience, light has been acting like clindamycin. Some hours after the light exposure, I get an increase in IP that feels for all the world like the IP I used to get from clindamycin. That was not my experience in the early years of the MP.
I sat in the reception area, just for once not looking out of place in my Noirs as he is a low vision specialist. It was great to feel normal and not get funny looks.
The point I am getting at is that all was OK until I took off my NoIRs and spectacles for the eye examinations. I had previously explained my circumstances to him and briefly the MP. As soon as I took them off, I started overheating and sweating. I explained what was happening and he turned off the fluorescents in the room (no windows). After a few minutes I was OK again. He noticed this and commented. I had his full attention from then on.
I did go to Wal-Mart and because I was buying some clothes I needed to see the colors, so I didn't have my NoIRs on…so payback… got that old familiar feeling like low blood sugar with sweating and weakness. It hit me after about 30 minutes in the store. Got my NoIRS on quick and got out…didn't sleep well that night. Took a number of light attacks to make me a believer.
One interesting development is my anxiety level is way down…it has been for a while…I feel calmer than I can ever remember. I believe that started to happen with the light deprivation. Avoiding light is obviously very important and is doing some interesting things.
Aunt Diana, MarshallProtocol.com
I have recently started the MP, and have only just now realized that most of my discomfort, which has included pounding heart and shortness of breath, is connected to too much light exposure. I seem to need real darkness, period. Well, no, at night I feel better, even if I don't wear my glasses. But during the day, there seems to be no place dark enough.
Especially early on, I got really confused about what the appropriate amount of light is. What really threw me for a loop was how I seemed not to be noticeably affected by my cubicle environment, but then I started wearing my shades 100% of the time at work and behold, my insomnia went away! So, I was sensitive, but not in a way that was immediately perceptible. It made me think twice about going with my gut when it came to light sensitivity.
Natural light is to a minimum now. Have made more adjustments at work and at home. You were right! I was getting tired and weak because of light exposure. The last few days has been a big difference.
A neural mechanism for exacerbation of headache by light.7
Noseda R, Kainz V, Jakubowski M, Gooley JJ, Saper CB, Digre K, Burstein R. Department of Anesthesia, Boston, Massachusetts, USA. Comment in: Nat Neurosci. 2010 Feb;13(2):150-1. Abstract The perception of migraine headache, which is mediated by nociceptive signals transmitted from the cranial dura mater to the brain, is uniquely exacerbated by exposure to light. We found that exacerbation of migraine headache by light is prevalent among blind individuals who maintain non-image-forming photoregulation in the face of massive rod/cone degeneration. Using single-unit recording and neural tract tracing in the rat, we identified dura-sensitive neurons in the posterior thalamus whose activity was distinctly modulated by light and whose axons projected extensively across layers I-V of somatosensory, visual and associative cortices. The cell bodies and dendrites of such dura/light-sensitive neurons were apposed by axons originating from retinal ganglion cells (RGCs), predominantly from intrinsically photosensitive RGCs, the principle conduit of non-image-forming photoregulation. We propose that photoregulation of migraine headache is exerted by a non-image-forming retinal pathway that modulates the activity of dura-sensitive thalamocortical neurons. PMID: 20062053
Depressed people actually 'see' the world around them in shades of gray, at least subconsciously, a new study suggests.
German researchers used retina scans to monitor the response of the retina to varying black-and-white contrasts, and found that depressed people had dramatically lower retinal response to contrast than those without depression.
This lower response was evident in depressed patients regardless of whether or not they were taking antidepressants. The researchers also found that people with the most severe depression had the lowest levels of retinal response to contrast.
The University of Freiburg team said though more studies are needed, the findings suggest retina scans could eventually be used to diagnosis and measure the severity of depression, as well as assess the success of therapy. This method may also prove valuable in research.
Biol Psychiatry. 2010 Feb 1;67(3):270-4. Epub 2009 Oct 14. Retinal response to light in young nonaffected offspring at high genetic risk of neuropsychiatric brain disorders.
Hébert M, Gagné AM, Paradis ME, Jomphe V, Roy MA, Mérette C, Maziade M. Centre de recherche Université Laval Robert-Giffard, Québec G1J 2G3, Canada. firstname.lastname@example.org Comment in: Biol Psychiatry. 2010 Jul 15;68(2):e3; author reply e5. Abstract BACKGROUND: In neuropsychiatric brain disorders, such as schizophrenia (SZ) and bipolar disorder (BD), the biased effect of chronic drug therapy and the toxic effect of illness once installed constitute obstacles to the identification of valid biomarkers. Such biomarkers could lie at the level of retinal function where anomalies have already been reported in adults suffering from neuropsychiatric disorders. Here, we report a specific electroretinographic (ERG) anomaly in young nonaffected and nonmedicated offspring at high genetic risk (HR) of these disorders. METHODS: Electroretinography was performed in 29 HR offspring having one parent affected by DSM-IV SZ or BD (mean age: 20.8 years, SD 4.4) and 29 healthy control subjects (mean age: 20.6 years, SD 4.2). The HRs' parents descended from multigenerational families affected by SZ or BD. RESULTS: Rod ERG (b-wave amplitude at V(max)) in HRs was significantly lower than control subjects (p < .0001; effect size of -1.47), whereas the cone ERG V(max) showed no difference (p = .27). No effects of gender, age, and seasons of testing were observed. The anomaly in retinal response (rod V(max) b-wave amplitude) was observed independently of parents' diagnosis (SZ; p = .007, effect size of -1.09; BD: p < .0001, effect size of -1.88) and was present in both the younger and older HRs (effect size of -1.6 and -1.8, respectively). CONCLUSIONS: A rod retinal response anomaly before the age of the disease incidence may represent an early and specific biomarker of risk with meaning for further genetic and prevention research. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved. PMID: 19833322
Bacteria in the eyes
“I recently showed that 1,25-D directly activates the Rhodopsin receptors in the retina of the eye. These are the sensors for light. They work in a complicated fashion, so I won't attempt to explain it here, but it is the high 1,25-D level due to killing of the intra-cellular bacteria which is causing your optical phenomena, not the meds. OK, well, it is due to your taking the antibiotic meds, but only indirectly.
The retina of the eye sees a spot of light when a number of receptor molecules, rods or cones, are excited by photons of light. The Xray structure of the rods (Rhodopsin) is known. I have found that 1,25-D binds with high affinity into these. Most scientists seem to think that a cluster of about 5 need to be triggered by photons in order for the brain to see a spot of light. When 1,25-D levels are very high in the eye itself, then some of these rod receptors will always be excited, by the 1,25-D. One member has reported tiny white 'snow flake spots' in the darker parts of an image. The experience of 'glare' sounds similar. So do the more common “floaters.” ..Trevor..
Dec 07 “The rod receptors in the eye are GPCR, similar to Angiotensin-II receptors. There is an Xray model available for Bovine Rhodopsin, and I used that to show that not only are the receptors activated by Retinal, but 1,25D has a high affinity for them too. I am guessing that the receptors are activated by 1,25-D (rather than de-activated), but we don't know enough about the eye to say that just yet.
It is believed that when a pool of about 5 adjacent receptors are simultaneously activated, the electrical signal so produced is sufficient to produce a pulse on the optic nerve. So sight is not based on a single receptor, but on a pool of adjacent receptors. When receptors are activated by 1,25-D (being formed in the eye by incident radiant energy), it will activate vision, but presumably by providing a continuous random stimulus. The optic nerve and brain then have to try and sort out where an image is, based on a consensus of false and true signals from the receptors in the retina.
Additionally, 1,25-D has the role of activating the VDR to produce several key proteins for the retina, without which the retina cannot remain strong and functional. The bacteria in the eye will obviously affect this process of transcription, which is probably why ocular symptoms (floaters, etc) are so common in these diseases.” ..Trevor..