I'm busy working on my blog posts. Watch this space!
Porphyria (2 of 2)
October 7, 2019
Porphyria is considered to be a rare disease by the medical community. However, I believe it is underdiagnosed, and I also have reason to believe a type of "secondary porphyria" can exist for those that have external causes (such as toxicity or infection) that can create the symptoms of porphyria by also interfering with the heme process, even if one tests negative via genetic testing.
In this post, I will discuss my opinions and thoughts on Porphyria, including possible underlying causes and support ideas. I will also share my story in dealing with Porphyria.
Several nutrient cofactors have been found to be important to the enzymatic function of each gene. Because of this, some countries still successfully treat Porphyria with nutrients, and in particular, B vitamins.
However, in my opinion, since the U.S. is so focused on marketing and selling pharmaceuticals, research & education on, and treatment with nutrients and vitamins has largely been forgotten and fallen by the wayside. It seems that this information is not widely known by US-based doctors, even those very familiar with Porphyria.
There are studies that have demonstrated succesful treatment of various porphyrias with the following vitamins and minerals (note some of those were in addition to small to moderate amounts of glucose syrup):
Type of Porphyria - Nutrients Used in Treatment:
AIP - treated with vitamins B6, B9 (folate), B-complex, and minerals Zinc, Magnesium.
VP - treated with vitamins C, E.
HCP - treated with vitamin B2.
PCT - treated with vitamins B1, B2, B3, B6, B9, B12, C, E.
EPP - treated with vitamins B6, C, A, the mineral Zinc, and the amino acid NAC (N-Acetyl Cysteine).
CEP - treated with vitamin B6.
In addition, the following vitamins, minerals, and nutrients are known as being required for and integral to the following processes and enzymatic functions.
Also, remember that the first step of the heme process requires glycine + succinyl-CoA (which is supplied from the TCA Cycle).
Nutrient Cofactor - Required for Biochemical Process:
B1 (thiamin) - TCA Cycle
B2 (riboflavin) - TCA Cycle, PPOX
B3 (niacin) - TCA Cycle
B5 (pantethenic acid) - TCA Cycle
B6 (pyridoxine) - ALAS, FECH, Glycine synthesis
B7 (biotin) - TCA Cycle
B9 (folate) - Glycine synthesis, PBGD, UROS
B12 (cobalamin) - TCA Cycle
Lipoic Acid - TCA Cycle, UROD
Iron - TCA Cycle, CPOX, FECH
Sulfur - FECH
Zinc - ALAD
Copper - FECH
Dealing with Symptoms
The current traditional medical treatment of the acute porphyrias includes:
-Giving high amounts of glucose to halt an attack. Glucose slows down the initiation of the heme process. This gives the liver and detox systems a chance to "catch up" and clear out the byproduct toxins, without the system continuing to become backlogged. During major attacks, glucose is given intravenously. For minor attacks, "carb-loading" and eating dextrose or glucose/sugar tabs can help for some. Note that giving glucose is just a "band-aid" and doesn't do anything to actually resolve the busted heme process.
-Giving heme intravenously also halts the heme process. This is because the body senses sufficient heme, due to the feedback loop previously discussed, so it stops the signal to continue producing heme (which also then results in lower amounts of the toxic intermediate porpyrin compounds). Giving heme also does not actually resolve the issue, but instead, relieves symptoms temporarily.
-Phlebotomy treatment (which lowers iron in the body) as well as the drug Plaquenil (an anti-malarial that is also frequently used to treat Babesiosis) have been shown to be helpful with PCT.
-Avoiding triggers is huge with porphyria. Depending upon the person and the type of porphyria, these triggers can include:
Sunlight and some artificial lights, stress (including over-exercise), hormones (both estrogen and progesterone have been noted), fasting and low-carb diets, some drugs and medications, some supplements and herbs, high histamine and/or high sulfur foods, toxin and heavy metal exposure (lead and other heavy metals also disrupt the heme synthesis pathway), as well as infections/pathogens.
Regarding medications, herbs, and supplements: anything that affects the liver and induces CYP450 enzymes is known to aggrevate porphyria, as the induction of CYP450 upregulates the heme process. The American Porphyria Foundation has a drug database that can be found here: https://www.porphyriafoundation.org/drugdatabase/
Drivers of Porphyria & The Infection Connection
During my research, I discovered that the vast majority of people with mutations of the "porphyria genes" are asymptomatic. Only between 10-30% (I've heard varying numbers...the new research is saying closer to 10%) of those with the genetic mutations experience porphyria symptoms.
So, as the minority of those with the genetic markers actually become porphyric, there have to be additional underlying drivers that "flip the switch." One researcher hypothesized that a main driver could be lack of B6 (I myself have had low B6 markers for years, despite supplementation). However, I believe it runs deeper than that. I believe there is an infection connection, at least with some patients.
Although Porphryia is considered rare, it seems it is possibly not as rare within the Lyme community when compared to the general population. It is possible that the increased toxic burden carried by those with Lyme and mold-related illness compromises the liver and mitochondria, and therefore, also the heme synthesis process. We know that the mitochondria also "slow down" as part of the CDR (Cell Danger Response).
Another possibility is that some pathogens more directly hijack the heme process, including Babesia and Bartonella, pathogenic bacteria which both have an affinity for heme and therefore also the major tissue sites for heme production: the bone marrow and liver. These pathogens cannot create their own heme, so they scavenge it and precursors from their hosts.
One of the first thoughts I had when I began researching Porphryria was how the pathogenic bacteria Babesia and Bartonella "love" heme. As a side note, I have previously tested positive for both of these bugs, and based on symptoms, they have been some of my larger issues (possibly larger than Lyme/Borrelia itself).
Since porphyria is considered a rare disease, studies in many areas are lacking. This includes studies on the possible link between Porphyria and pathogens/infections such as Babesia and Bartonella. However, after MUCH digging, I did find ONE study from Peru completed in 1961 titled "The Hemolytic Anemia of Human Bartonellosis." This study very briefly mentioned a link:
"It seemed interesting to study the free protoporphyrins in the red cells as well. In table 5 is presented the average obtained in 7 patients with bartonellosis, compared to that obtained in 12 normal subjects. The increase of this hemoglobin precursor was marked, reaching 190.4 mcg per hundred cc. of red cells in the Bartonella patients, while the level in the healthy subjects was 30.6 mcg." (source)
Regarding Babesia, here is one comment in a study titled "The Heme Biosynthesis Pathway Is Essential for Plasmodium falciparum Development in Mosquito Stage but Not in Blood Stages" regarding this pathogen's reliance on scavenging heme:
“It is interesting to note that some Apicomplexan parasites, such as Theileria and Babesia species, have lost the heme biosynthesis genes and must rely entirely on scavenging mechanisms to acquire heme molecules.” (source)
Also, of note, is that the drug Plaquenil (previously mentioned as used in treatment for the PCT type of Porphyria) is also effective against Babesia. Perhaps this is partially why Plaquenil works for at least some types of Porphyria? I could not find where Plaquenil was tested for other types of Porphyria, so I'm unsure of it's effectiveness for more than PCT.
I won't get into the distinction between "primary" and "secondary" Porphyria at this time, as there is currently much debate about what constitutes each, and since most of those with the genetic markers are asymptomatic, it seems that most porphyrias would then be considered "secondary" as they are triggered by something else. So, in my opinion, possibly "primary" and "secondary" designations are just semantics.
There are many other microbes that scavenge heme, or are known to have an affinity for heme, such as Malaria and Trypanosoma cruzi (which causes Chagas Disease).
Based on this preliminary info, and knowing some of the mechanisms of these pathogens, I think further research on the possible links between Porphyria and pathogens is more than warranted.
Above, I discussed the traditional ways in which Porphyria is treated (including glucose, heme IV's, and avoiding triggers). The glucose and heme are simply "band aids" and do not actually resolve the busted heme pathway.
I have yet to find a good source on clear tried-and-true natural or holistic Porphyria support, so much of what I'm including below is speculation and my opinion on being possibly useful in Porphyria. This is also currently limited to myself as my own guinea pig, since Porphyria is still quite rare.
In Neil Nathan's book "TOXIC" - link here - (where I first learned of Porphria), he discusses that the use of activated charcoal as a binder can be helpful for decreasing circulating porphyrins.
There is also a comprehensive book titled "Porphyria: The Ultimate Cause of Common, Chronic, and Environmental Illnesses - With Breakthroughs in Diet, Supplements, and Energy Balancing," by Steven Rochlitz. This book has a lot of great info and is the only naturally inclined book on Porphyria (that I've been able to find). It has a lot of good info, however, I found it a little hard to follow, with some of the supplements that could help or harm contradictory and with no clear "plan of action." Perhaps that is just my opinion, as I've seen others state that they found this book very helpful.
The most helpful comprehensive source on Porphyria that I found is a thesis paper from New Zealand titled "Investigating the Porphyrias Through Analysis of Biochemical Pathways," by Evonne Teresa Nicole Ruegg. She goes over the links between the Porphyrias, vitamins, and nutrients (which I summed up in this post). You can find the complete paper here.
My thoughts on possible Porphyria support
-Deal with the Trigger. This might possibly include ANYTHING that increases toxic load on the body (and liver). Heavy metals, environmental toxins including high EMF's, mold exposure, underlying infections, and/or pharmaceutical drugs that affect the liver or mitochondria.
-Support with Antioxidants. Porphyria has been described as a "hyperoxidative" state. Therefore, using antioxidants can be of help with calming the fire. The use of Vitamins C and E have been shown in studies to be helpful in acute attacks. NAC (N-Acetyl Cysteine) also has at least a couple of studies showing benefit with Porphyria (one here). Increasing SOD (superoxide dismutase) may also be helpful, as well as Lipoic Acid, which is a known cofactor of some heme processes. The master oxidant glutathione (or precursors) might also show benefit. A note on supplementation: I prefer to use whole food sources whenever possible. Please don't supplement willy-nilly without first doing research and/or consulting with a practitioner.
-Support Liver and Detox Pathways. Since most of the heme synthesis occurs in the liver, supporting the liver could prove helpful in those with Porphyria. On one forum, I noted multiple Porphyria patients mention benefit from use of the herb milk thistle / silymarin. NAC, glutathione, and precursors, as mentioned above, can also help in this category, by assisting the liver with detoxification. Dandelion tea is a good gentle liver support that might be tried as well.
Since I knew SAM-e was helpful with liver toxicity, I searched and found a couple of studies that demonstrated it was useful in at least one type of porphyria (one of these studies here).
Lymph support, including consistent and gentle movement, may also decrease some of the systemic toxic burden.
-Support the Mitochondria, and replace needed Nutrients. Many of the vitamins and nutrients mentioned as being cofactors of the heme synthesis processes are also important for mitochondrial health. This includes B vitamins, Lipoic Acid, and vitamins C & E. Vitamins A & D are also important, although I prefer food sources over synthetic. The amino acid L-Carnitine has also been very beneficial for me. Since the mitochondria are integral in the heme synthesis process, it makes sense to give them what they need to do their job properly. Remember again to please consult with a practitioner prior to supplementing, especially with synthetic / non-food sources.
Red light can also help mitochondria, however, one should be careful as some sources of light can also trigger attacks in some. For me, infrared sauna (~800+ nm wavelenght) is beneficial, but I currently can't do sunlight or 650nm or lower wavelenghts. 400-450nm has been shown as the most triggering wavelength for porphyrins.
Having optimal thyroid function and levels is also tied to mitochondrial health and energy. Therefore, supporting the thyroid might also help, if warranted.
-CYP Inhibitors. I couldn't find any studies or anecdotal evidence on this, but it made sense to me that if CYP inducers can trigger porphyria attacks, then CYP inhibitors could perhaps calm or decrease attacks. I then looked up many of the "calming" herbs that I was taking via the Buhner Protocol that have been helping me (Chinese Skullcap, Red Sage, and Kudzu...all in powder form, not alcohol tincture), and sure enough, they are CYP450 inhibitors. CBD (cannabidiol) is another potent CYP inhibitor (source). I'll add more to this list in the future.
Increasing histamine support (such as natural anti- or pre-histamines) can be helpful if the hyperoxidative state of porphyria is causing histamine issues. Some strains of probiotics can degrade histamine, including those found here. Nettle leaf, quercetin, and bromelain can also be helpful in those with histamine issues.
Decreasing inflammation may also be helpful. Some natural anti-inflammatories include quercetin, bromelain, turmeric, hydrogen water, Alka-Seltzer Gold, and enzymes such as serrapeptase.
Since ALA blocks GABA receptors and causes many symptoms of over-excitability and anxiety/panic, natural GABA agonists might be helpful for dealing with symptoms, such as L-Theanine, Chinese Skullcap, or Magnolia Bark.
-Increase Carbs. Low carb diets are not your friend if you are currently dealing with Porphyria. You may need to increase carbs and/or work with a nutritionist to come up with a sufficient meal plan.
-Work on Breathing. Many with Porphyria have low CO2 (bicarbonate) levels (I did for over a year). Dr. Neil Nathan and others have noted that working on changing breathing habits and patterns to include CO2 retention (breath holding, slow exhale, and/or breathing through a paper bag) may help with a Porphyria attack.
As always, use caution when trying any new supplement or herb. Do your research and consult with your Doctor. Since porphyrin reactions build over time, one may not notice that something triggers an attack until several days post-introduction. Introduce anything new slowly and keep a daily symptom/food/supplement journal.
-Decrease Stress. This is a common theme you'll hear in all of my posts, because it's so important. Learn ways to manage stress - deep breathing, taking breaks, putting down the phone and being quiet, taking a walk, saying no. Whatever you need to do to work on this.
Getting in higher levels of carbs on a more paleo-type diet can be a challenge. I'm including some ideas here, in hopes that it may be helpful for others in the same boat. I have been low carb for years, so a higher carb diet is a still a bit foreign to me.
Bananas / banana chips
Plantains / plantain chips
Unsulfured blackstrap molasses~
Dates, Medjool dates
Beans (not technically paleo)
Raw cane sugar
~note this is also high in iron, which could be good or bad, depending upon the person.
*some note issues with red fruits, so be aware.
My Experience with Porphyria
I have not had any skin symptoms of Porphyria, but only neurological symptoms. Most of my Lyme & coinfections symptoms over the last few years have been neurological. I'm unsure how much of that has been tied to Porphyria.
I think I was in some form of attack for the better part of the last year. It started with an extended period of fasting. I noticed the shift then, and two days later I went full hyperthyroid. After I focused on and resolved the hyperthyroidism a few months later, I still had near-constant issues with anxiety, panic, neuropathy, and other neurological symptoms. I am a pretty decent detective, and could not find a common pattern with foods, supplements, etc.
It only made sense in hindsight that I was dealing with Porphyria during this time, after I had a test result come back high for four different types of porphyrins via urine...and this was during a good and more asymptomatic couple of weeks. Remember from post #1 that patients are normally supposed to test during a symptomatic period, as this is typically when porphyrins would show high on testing.
I also later found a study showing that porphyria can trigger hyperthyroidism (possibly due to the fact that porphyria is a "hyper-oxidative" state, so any area of the body prone to inflammation or weakness could then potentially become inflammed or angry).
Once I realized I had likely been experiencing porphyria, I further confirmed this to myself via trial and error. Sure enough, sunlight or certain wavelengths of artificial light, lowered amounts of carbs, fasting, other triggers such as alcohol in herbal tinctures, and a lack of certain nutrients would begin the "building" of symptoms.
For me, it would start with feeling more fatiged than usual, and then I would feel out of breath more easily. Next, I would feel anxiety starting, and then building each day. I knew this was a biochemical anxiety and not driven by my mind or limbic system (which is also a challenge for me that I consistently work on and am making progress with).
The anxiety would turn to true panic, where I had to use all of the calming skills in my toolbox to stay somewhat functional (even just at home) and keep from completely losing my shit and jumping out of skin. Things like driving only 5-10 mins or grocery shopping 15 mins were completely out of the question at this stage, as they were too overstimulating. Brain fog, inability to concentrate, and tasks like finding words would also be intense. My brain would also feel "glitchy" (I have no better way to describe this feeling). I would also begin to have parasthesia (numbness & tingling) in my limbs, especially at night upon laying down.
I would start to feel hypoglycemic 24/7 (very weak, shaky, and lightheaded, dizzy), no matter how much, how often, or what I ate. I would have to eat almost constantly just to keep some of the edge off. I would also get tachycardia, from the inflammation and what I think was also an increase of norepinephrine in my system. I would feel excessively hot during these periods, too.
My whole body would feel inflamed. So, it was essentially a shit storm of inflammation. It is very hard to describe how I felt during an attack, but the inflammation + neurological symptoms felt like pure hell. Like "can't function, laying on the floor crying and just praying for a break" kind of hell. I had also developed a tremor 24/7 due to the inflammation and apparent decrease in GABA.
I was also reacting to foods with histamine and mast cell symptoms, which would cause an increase in anxiety, insomnia, flushing, tachycardia, etc. I was reacting to most supplements and herbs, even ones I had taken for years with no issues. I was (and still currently) reacting to alcohol tinctures, although my tolerance has increased to where I can now take a couple per day.
It's ironic that once I started increasing my carbohdrate intake (including GF "junk foods" that I hadn't eaten in years; I had kept to a "perfect" and very strict paleo type diet for years), my symptoms quieted, including the histamine issues. So, by widening my types of foods to include some levels of junk food, I was able to tolerate MORE foods overall, to the point of going from reactions to most things, to being able to eat anything (except gluten, which I steer clear from), in only a matter of a couple of weeks. This really challenged my prior view of a "perfect diet," and I'm now no longer quite so rigid and strict with my foods.
I also had periods prior to discovering porphyria where I would wake in the middle of the night with what felt like a panic attack: tachycardia, sweating, sheer panic, shaking, tremors. Some nights it would start before I fell asleep. This was happening most nights and would last from about 11 pm to 6 am, which I think coincided with decreased cortisol, which probably helped to keep the inflammation at bay during the day.
I noticed via trial and error that this would become less frequent when I ate carbs just before bed (I also tried protein, but it didn't abate these attacks, only carbs would). High sulphur foods at dinner (hours before...at 6 pm) also increased the attacks, and therefore, molybdenum supplementation (which helps to process sulfurs) helped dramatically decrease attacks.
Also, after increasing my carbs, besides the neurological symptoms abating (often quite dramatically night-and-day difference, going from WEEKS of intense panic, to some level of calm, within literally just a couple of HOURS after carb-loading 100-200g in one sitting), my energy also increased and I was able to start working out again, at levels I had not been able to achieve in many years.
I do still struggle with some fatigue and vestibular / cerebellum issues, but I continue to work on those and am hopeful for a full recovery soon.