Chris Masterjohn, PhD, is one of my favorite researchers worldwide. Here’s his recent explanation of how he deals with allergies. He writes:
On Thursday, April 28, I was planning on finishing my vitamin C report (see the preliminary report here), but my plans got temporarily upended by the onset of seasonal allergies.
My Experience With Allergies This Month
I woke up in the middle of the night with an irritated throat from post-nasal drip. I thought I might be catching a cold, so I went to the bathroom, sprayed some Betadine Cold Defense into each nostril, and went back to bed. When I woke up, my throat was still irritated and I felt a bit mucousy.
The Weather Channel app reported “very high” pollen counts, but low flu and COVID cases, which made me think it was allergies. However, the fact that it came abruptly in the middle of the night seemed to contradict that. I started implementing my COVID protocol (free to paid Substack subscribers here), figuring much of it would help with allergies or colds rather than just COVID and it is better to start early if I’m getting sick.
It seemed to be helping and I got better through the day until I spent 40 minutes outside in the afternoon. Around the 40-minute mark, my nose started dripping slightly. This made me even more convinced it was allergies, but, just in case, I rinsed my nose out with 0.5% povidone-iodine solution. This would stop any nasal symptoms if I were getting sick, but it actually made me sneeze a bit. In contrast, I later rinsed my nose out with a neti pot full of salt water in each nostril and it dramatically reduced the symptoms. At this point, I became completely convinced it was allergies.
I thought about it a bit, and then realized that on April 27 I had my windows open all throughout my apartment to cool the place down before bed. It was extremely windy, and the pollen count was “very high.” My bedroom window is directly over my bed, which means that I had pollen blowing onto my bedsheets and pillow all day long. The night I first woke up with post-nasal drip, I must have been rolling my face back and forth in the pollen on my pillow case for hours.
Once I realized this, I changed my sheets and made a point of showering, changing my clothes, and rinsing my eyes and nose out when I come in from outside and before I go to bed. This helped a lot, although it didn’t completely solve the problem.
One thing I noticed is that people all over the place were complaining how bad their allergies were. At the coffee shop, friends at church, no matter where I went, people were complaining about it and my allergies were rather tame compared to many people around me.
Nevertheless, the post-nasal drip made me have to sleep with my head elevated using a second pillow, the quality of my sleep suffered (for example, my resting heart rate was elevating), and I felt a little foggy-headed during the day.
I then turned from the vitamin C report to doing some research on allergies so I could put together a protocol that would help maximize my well being and work productivity without taking any medications.
In the days where I started implementing this protocol, rain came in and washed the pollen away, giving me time to start reaping the benefits of my protocol before the pollen came back.
A few days ago, the pollen counts started rising from “moderate,” to “high” again, with tree pollen reaching “very high” today. At first it was a little misty or drizzling out, and I didn’t experience any allergies at all.
It is now the third sunny day with pollen counts “high.” I believe my allergies are some 80-90% better since starting my protocol. Not once have I had to sleep with an elevated head. Yesterday I was working outside for hours without developing a runny nose, whereas prior to the protocol my nose would start dripping around the 40-minute mark.
However, I did wake up last night with an itchy throat. I may have woken up because I have not yet put air conditioning in my bedroom this year and the temperature got up to 74. I sleep best with a ChiliPad when the temperature is under 70. I also felt hungry.
I rinsed my nose out with a neti pot, went back to bed, and followed a breathing pattern that usually helps me sleep (inhale for four, hold for four, exhale for six, hold for two, repeat ten times). I didn’t fall back to sleep, so I got up and took 3 grams of glycine to help cool my body temperature. Since I was hungry, I also took 3 milligrams (mg) of melatonin. In my experience, 10 mg of melatonin allows me to sleep even on a 50% caloric deficit, so I figured 3 mg would help me sleep if I were hungry in the middle of night on a calorically neutral diet.
The melatonin I had on hand was Olly’s Sleep gummies, which also have 75 mg of theanine, 17 mg each of chamomile and passionflower extract, and16 mg of lemon balm extract. Dean Kanargelidis had commented on a YouTube video a few days ago asking me if I thought theanine had use as an anti-histamine. As it turns out, there is some research suggesting it has anti-histamine properties.
As an experiment, I sucked on the gummies to see if the theanine being released into my mouth would make my nose and throat feel better. There are two gummies per serving. Remarkably, by the end of the second gummy, my nose and throat felt completely clear. I repeated my breathing pattern through clear nostrils, immediately fell asleep, and slept well through the rest of the night.
I will follow this up with some experiments to see if theanine alone can reliably be used to stop acute histamine-related discomfort and report back when I have findings.
Now, though, I turn to the protocol that seems very much so far to be working.
This is not a complete review of all supplements that have effects on allergies. My research assistant is putting together all of the relevant studies for me and I will be reviewing them more completely next week. This is what I was able to quickly find was effective to put into an immediate action plan for myself.
3 grams of Spirulina Per Day
Compared to a placebo, 2 grams of spirulina per day decreases allergic symptoms in the off-season up to about 75%. The effect seems to be very small in the first two weeks, emerge more clearly at week 3, and reach maximum after it is being taken for four months.
Compared to 10 mg per day cetrizine (Zyrtec) taken for two months during the off-season, 2 grams of spirulina significantly outperforms.
These studies used the off-season so that there would be less variation in allergies as pollen counts of different species went up and down. This reduces statistical noise and makes it easier to see the signal. The downside is it is not as clear how it performs during the pollen season.
Spirulina appears to work by shifting the immune system toward a less allergic-type mix of cytokines, and appears to take a couple of weeks for its effect to start. I think it’s safe to assume that Zyrtec would be much more effective when taken for the first time in response to an acute reaction, but it’s very notable that after two months people are generally experiencing less allergies taking spirulina every day than taking Zyrtec every day.
Spiulina products usually suggest 3 grams per day as a serving. I also wanted an effect that is stronger than 75% and kicks in quicker, so I went with 3 grams per day.
2 Capsules of “Tinofend” Per Day
In one study, 300 mg of the Indian herb Tinospora cordifolia three times a day (900 mg/d total) for 8 weeks, compared to placebo, was highly effective at reducing allergies during an unspecified time of year. Depending on the specific symptom, 60-83% of people reported complete relief at the end of the study, and most of the rest reported 75% relief.
By contrast, most people in the placebo group reported no relief or 50% relief, and very few reported 75% or 100% relief.
Tinospora has evidence as an immune regulator, but it isn’t clear how long it takes to have an effect within the 8 weeks of this study.
I found this as the sole active ingredient of Life Extension’s Tinofend Immune Modulator, where 900 mg is achieved with two capsules, so I added two capsules of this a day to my regimen.
I found two randomized, controlled trials that were clearly testing the effect of local, raw, unfiltered honey on seasonal allergies to pollen.
Both pursued the hypothesis that small amounts of pollen in the honey would desensitize the person to pollen in the air, although they acknowledged that honey could also have anti-inflammatory effects.
The first found no effect at all. It had a very good placebo made from corn syrup and honey flavoring that was optimized during taste tests to taste just like honey. It compared this to supermarket honey and to local, raw, unfiltered honey. It did not analyze the pollen in the honey. The subjects consumed one tablespoon per day, starting at the beginning of the tree pollen season. No instructions were given about how to consume the honey except to consume it in one dose or in three divided doses.
The second found a very strong effect. It did not use a placebo. It compared an untreated control to “regular” local, raw, unfiltered honey, and to the same honey with birch pollen added to it. Control subjects knew they were the controls, but the others were blind to which honey they were getting.
The subjects were diagnosed specifically with birch pollen allergy. The birch pollen honey had 600 times more pollen than the “regular” raw honey. Most of the pollen in both honeys was willow pollen, but birch and alder pollen were only found in the birch pollen honey.
The subjects were instructed to begin consuming the honey five months before the birch pollen season. They started with a drop containing less than one gram, and gradually worked their way up to one teaspoon per day. They were not allowed to mix the honey with any drinks or food. They had to keep it in their mouth for several minutes and mix it around their mouth and up against their palate with their tongue before swallowing.
The honey regimen was finished by the end of March. After that, birch pollen season began and symptoms were recorded.
The birch pollen honey led to a 59% reduction in symptoms. The “regular” raw honey was intermediate between the birch pollen and control, achieving a 34% reduction in symptoms, but wasn’t statistically significantly different from either of them.
This same pattern — birch pollen honey most effective and “regular” raw honey intermediate — was replicated throughout most other metrics. This was true for symptom-free days, severe symptoms, “other symptoms” besides those of the nose and eyes, and how many antihistamines people took. “Regular” raw honey was almost as effective as birch pollen honey for eye and nose symptoms and for symptom-free days.
While one could point out the well designed placebo in the first study, the entire design of the second study is far better suited to the hypothesis that the pollen within honey acts as a form of immunotherapy.
If we compare it to sublingual immunotherapy, which delivers exact antigen sublingually, it probably works primarily by stimulating the immune system to make IgG antibodies to the pollen that compete with IgE antibodies. Since IgE antibodies are much more inflammatory and mediate allergy symptoms, competition from IgG antibodies for pollen-binding blocks the inflammation.
Generally it takes four weeks to develop an antibody response to immunotherapy, with the clinical benefit taking up to 12 weeks to set in, while the benefit may last up to two or three years after the therapy.
If we compare the two studies using this hypothesis, we can note the key differences:
- The first study did not start the honey until the pollen season started. The study went from March through the end of the summer, and it may have taken the first few months for a honey benefit to kick in.
- In the first study, the honey was swallowed. In the second study, it was held and massaged in the mouth for several minutes. The allergens could be digested after swallowing, and if they survive to reach the mucosal immune system of the gut, the immune response will be local and quite isolated from that in the mouth and nose. By contrast, swishing the honey in the mouth for several minutes allows the mucosal immune system of the mouth to respond. Migration of immune cells or pollen grains between the mouth and nose, moreover, is probably relatively easy. This may have even allowed a local immune response in the nose, then.
It is unfortunate that the first study did not have an untreated control, so we could see the actual placebo effect of the honey substitute. Based on a quercetin study in the next section, I would tentatively say that the placebo effect for a nutritional supplement against allergies will be roughly 20%. The effect of the “regular” local, raw, unfiltered honey in the second study was a 34% reduction in symptoms, quite a bit better than a plausible placebo effect.
I am inclined to believe that there is some cross-reactivity with different pollens, and that we may have seen the “regular” honey compete better with the birch pollen honey if the dose, and therefore the pollen being used, was greater.
I used localhoneyfinder.org to locate “hyperlocal” honey made from bees that live in my own neighborhood of New York City. I worked my way up starting with a half teaspoon per day swallowed right away to this dose three times a day held for increasing amounts under my tongue and moved around my mouth until I reached three minutes. I will now focus on increasing the dose over time.
I may add bee pollen to this, although the bee pollen I was able to find is not “hyperlocal” the way the honey is. I am also concerned about having an allergic reaction. In the birch pollen study, mild oral itching was commonly reported and one person dropped out due to “pronounced itching in the mouth.” My plan is to wet my arm, rub a pollen grain on it; if there’s no reaction, do the same on my wrist; if there’s no reaction, lick the pollen grain once; if there’s no reaction increase the number of licks and then eventually transition to a crumb of a pollen grain held in the mouth for increasing amounts of time, and keep working my way up like that. I have not started this yet.
250 mg Quercetin Phytosome
Rats can be made allergic to egg white by vaccinating them against it. This involves injecting them with egg white protein and aluminum hydroxide as an adjuvant.
In rats who are vaccinated against egg white, injection of 80 mg per kilogram body weight of quercetin over seven days lowers the amount of IgE they make to egg white protein dropped into their noses by 14-fold. In fact, it is just as effective as injection of steroids. IgE is a specific type of antibody that is the hallmark of the allergy response.
If we multiply 80 mg by 70 kilograms for the “standard reference man” and then divide by 6.2 to account for differences in surface area between rats and humans, we arrive at 903 mg. Divided over seven days, this is the equivalent of a human getting injected with 129 mg per day.
When we eat quercetin, about 1.4-6.9% is absorbed from food. Absorption of supplemental quercetin will be closer to the 1.4% figure if not modified in any way. Absorption of quercetin phytosome, which is mixed half and half with lecithin, is 18 times higher. Quercetin is fat-soluble, so fat and lecithin help its absorption. You may be able to replicate this effect by taking it with eggs (providing fat and lecithin) and butter (providing more fat), but this hasn’t been studied in humans. In rats, “enzymatically modified isoquercetin,” which has been modified to be water-soluble, is 17 times more absorbable than regular quercetin.
That means that 129 mg per day (mg/d) of injected quercetin, where all of it is absorbed, is the equivalent of 9,214 mg/d regular quercetin, 542 mg of enzymatically modified isoquercetin, or 511 mg/d of quercetin phytosome.
However, it is not that clear whether these are comparable, because injecting bypasses the intestines entirely and partly bypasses the liver. Quercetin is treated by our bodies as a xenobiotic (a foreign substance in need of detoxification) and by the time our intestines and liver get done with it, it mostly circulates as glucuronidated, sulfated, and methylated detoxification products.
Since the rat study only tested one dose, moreover, it isn’t clear whether a dose that high is needed to get the effect.
Nevertheless, if we look for whether the rat study can be replicated in humans, we are looking for a reduction in nasal allergen-specific IgE, or a clinical effect that would result from this, and we are expecting the doses needed to possibly be as high as 500-550 mg of quercetin phytosome or enzymatically modified isoquercetin, or over 9,000 mg of regular quercetin.
Two successive human studies have been published from the same authors of a supplement called “Lertal,” containing 150 mg of regular quercetin, 80 mg of perilla seeds, and 200 IU of vitamin D. Phase I was randomized, blinded, and placebo-controlled, and showed no effect at all. During phase I, everyone was also taking anti-histamines. In phase II, the subjects were unblinded, stopped taking antihistamines, and the placebo group stopped taking the placebo. After unblinding, on any given day, the Lertal users had about a 20% greater probability of not suffering from any worsening of their allergies.
Since there was no effect during the blinded phase, this is obviously a placebo effect and suggests that the placebo effect for a nutritional supplement against allergies is about a 20% reduction.
It is not surprising this had no effect as 150 mg/d of regular quercetin is wildly below the amount we would expect to need to see anything like what occurred in the rat study.
By contrast, two independent placebo-controlled trials (here and here) conducted by a single research group (a different group from the other two studies) found that, during the cedar and cyprus pollen seasons of Japan, 100 mg/d of enzymatically modified isoquercetin rather reliably cuts symptoms in the eyes in half. By contrast, it has relatively little effect in the nose except perhaps to help stuffy nose in some people.
These studies suggest that it takes at least 2-3 weeks for quercetin to kick into gear, and that it has the greatest effect when the pollen count gets the highest.
I have quercetin phytosome in my cabinet as part of my COVID protocol(free to paid Substack subscribers here), and the dose is 250 mg per capsule. Since I already have this formulation, I am taking one capsule per day, which is 2.5 times the dose used in the two successful human studies (which used enzymatically modified isoquercetin rather than quercetin phytosome), and is half the dose we would expect to need when generalizing from the rat study.
Of all the supplements I’ve included, I find quercetin to seem the weakest from the scientific literature, and I’m somewhat uneasy about using the high dose longer than needed. The quercetin content of foods ranges from, in each 100 grams, 2.47 mg in apples, to 17.22 mg in red onions, to 40.27 mg in red lettuce. On a very quercetin-rich diet, you might consume up to 180 mg a day and expect to absorb 7 mg of it. While I do think it deserves more study whether lecithin from eggs or fat more generally substantially increases the absorption, I am wary of perpetually consuming a dose of quercetin I could not get from food in a formulation that has 18 times better absorption, when I know that quercetin is treated by the body as something that needs to be detoxified and removed.
I am much more comfortable using quercetin phytosome temporarily when need arises. I will thus phase it out when I believe the rest of my allergy protocol has fully taken hold.
Vitamins, Minerals, and Diet
Anything added as an immunomodulator (spirulina, tinospora, quercetin), or immunotherapy (hyperlocal honey) should be added onto a diet that is nutritionally adequate, especially in the nutritional factors that reduce the potential for histamine release.
Vitamin A reduces mast cell burden, while oxidative stress and sulfite degranulate mast cells and cause them to release histamine. Molybdenum is the most important protection against sulfite, and sulfur amino acids (methionine and cysteine, most abundant in dairy and eggs and far more abundant in animal proteins than plant proteins) raise the need for molybdenum. The antioxidant nutrients include protein (especially the sulfur amino acids), vitamins E and C, selenium, zinc, copper, iron, and manganese.
The histamine content of mast cells and basophils is determined by methylation, where more methylation means less histamine. Betaine (trimethylglycine), which is synthesized from choline; riboflavin, folate and B12; and the sulfur amino acids stand out as the most important nutrients.
Antioxidant defense and methylation are both completely dependent on the system of energy metabolism, where sufficient calories; blood glucose that is neither too high nor too low; health of the thyroid, adrenal, and sex hormone axes; diabetes prevention; all of the B vitamins; and magnesium, iron, copper, and sulfur stand out as the most important nutrients.
Diamine oxidase is especially important to neutralizing histamine after it has been released. Copper and manganese have been shown to be needed for this enzyme in humans. Evidence from pigs suggests vitamin B6 is also needed.
My allergies were the worst when I was a teenager, living off junk food and smoking cigarettes. They got dramatically better when I made my way from veganism to a Weston A Price-type diet.
I believe the key things that stood out about my transition to a WAPish diet with respect to what I’ve outlined above were these:
- I made it a point to eat at least three eggs a day, instead of a maximum of one a day. This increased my methionine and choline, and promoted a more methylation-dominant state. This also made my diet much richer in the B vitamin biotin.
- I ate much higher animal protein, also leading to much more methylation.
- I replaced all refined sweeteners with natural ones, and ate copious amounts of raw honey.
- I ate a pound of buffalo liver per week, attempting to replete my vitamin A levels, which I had assumed were taxed during my vegan days.
- I ate a lot of raw animal foods. Animal foods, especially raw ones, are much richer in B6 than plant foods.
Other notable things that could play a role would be that I drank copious amounts of raw milk, I restricted my coffee intake, and I was in my early twenties.
I have long ago replaced raw milk with raw cheese, which doesn’t have the whey portion of raw milk, and therefore doesn’t have the glutathione-boosting potential, so critical to antioxidant defense. I use raw honey very intermittently now rather than copiously throughout the year. I drink more coffee now. I’m also much older, and I’ve accumulated inflammatory stresses such as a moldy apartment in 2016-2017, getting COVID twice (likely to have an allergy-exacerbating effect similar to what I would expect from COVID vaccines), and the Great Pscyho-Social-Emotional-Financial Stress of being alive anywhere on earth over the 2020-2021 period.
I haven’t rigorously tracked my allergies, but I do think they’ve gotten worse over the last two years. At least this year I’m not sneezing into a mask and inhaling my own pollen-filled snot anymore. I will never do thatagain.
If I look at my recent diet, during Lent it was lower in total protein, quite low in animal protein (I only ate shellfish for animal foods and occasionally supplemented with whey protein when I felt I needed it), high in folate due to frequent consumption of legumes, and low in choline due to the absence of eggs. I was only getting plant sources of vitamin A (I had intended to add krill oil but never got around to it). I was not eating much creatine, which reduces methylation demand, since creatine is only found in animal proteins.
Now — meaning just recently prior to making changes for the protocol — my animal protein intake is good, but I haven’t systematically gone back to a 3-egg-a-day habit.
My folate has dropped since I got sick of legumes and haven’t been consistently making leafy greens. My folate runs lower than my diet would suggest, likely because I practice rigorous sun exposure for my eczema, and go tanning when UV light isn’t available. UV light destroys folate in the skin. So my folate status is probably mediocre and dropping.
My vitamin A intake should be good for maintenance now that I’ve worked liver back into my diet, but I may be in a deficit from the Lenten period. Moreover, blue and UV light from my rigorous sun exposure will enter my light blue eyes and destroy vitamin A. UV exposure also raises vitamin D. Vitamin D is an important immunoregulator, but increases the need for A. Thus, I’m likely in a relative deficit of A and have a low A/D ratio.
When I get busy, my vitamin C intake often suffers. I’m quite busy right now and I do often run out of fruits and vegetables and have my C intake drop for a few days till I restock.
So these are the changes I made to address what I perceive as my most relevant personal deficits:
- Eat at least three eggs a day.
- For methylation support, 500 mg of TMG (betaine), 400-800 mcg methylfolate, and 5 grams of creatine per day.
- 10,000 IU of vitamin A in the form of retinol daily. Since my D status should be high and since fat-soluble vitamins deplete each other, I also take one Jarrow Tocosorb and 200 micrograms vitamin K2 as MK-7 each day.
- I take one capsule ofPaleovalley’s Essential C Complex twice a day to make sure I’m getting the maximally beneficial dose of whole-food C. Each capsule has 225 mg of vitamin C from whole food sources, and this is almost exactly the optimal dosing strategy (200 mg vitamin C twice a day) for maximizing blood and cellular levels without generating urate or oxalate.
My Personal Protocol
Overall, then, here is my personal protocol:
- 3 grams of spirulina per day, taken before breakfast.
- 450 mg Life Extension Tinofend taken once with breakfast and once with lunch.
- 250 mg quercetin phytosome with dinner or with any other fat-rich meal. I intend to phase this out over time.
- Hyperlocal honey, working up from small doses to larger ones and from small contact times in the mouth up to three minutes under the tongue and massaged throughout the mouth three times a day.
- Eat at least three eggs every day.
- 500 mg TMG taken with breakfast.
- 400 mcg methylfolate taken once with breakfast and usually also once with lunch.
- 5 grams of creatine with breakfast and another 2.5 grams taken with lunch, in each case taken before the meal.
- 10,000 IU vitamin A as retinyl palmitate, paired with one Jarrow Tocosorb and 200 mcg MK-7 per day, with dinner or with any other fat-rich meal.
- OnePaleovalley Essential C before breakfast and one before lunch.
I plan to experiment with bee pollen, being careful about an allergic reaction, and with theanine as an acute anti-histamine.
Gregory Patrick commented on yesterday’s post that raw milk completely eliminated his allergies decades ago. I have not drank raw, whole milk (as opposed to raw cheese) for years. However, I signed up for Essex Farm’s CSA last week, in order to follow my own recommendations for preparing for the emerging food crisis and do my part to support regenerative agriculture. I put a quart of raw milk in this week’s order just to try it, and they delivered it to my doorstep just before I sat down to write this article.
So I drank my first glass of raw milk in years while writing this. It was delicious, and it felt really good to drink it. If I think it helps my allergies, I will report back.
Adapting the Protocol
I believe the supplements are likely to be helpful to most people and can be adapted as is.
For the diet, I think it’s important to think through which nutrients are likely to be the missing links. The easiest way to do that is to use my Vitamins and Minerals 101 Cliff Notes (free to paid Substack subscribers here).
As noted above my research assistant is compiling all of the human studies on supplementation and allergies and I will produce a more systematic review for you next week.
In the mean time, what have you done to help your allergies? Let me know in the comments!
I am not a medical doctor and this is not medical advice. My goal is to empower you with information. Please make all health decisions yourself, consulting sources you trust, including a caring health care professional.
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