FAQ Episode 90: COVID and migraine biophysiology

Frequently Asked Questions about Natural Migraine Relief

May 29, 2025

If you have migraines and also had a bout of COVID, or took the mRNA COVID injection in the past few years, this post is for you. I’ve had patients with migraines who run the spectrum from “had COVID twice, never affected my headaches” to “did fine initially with the vaccine, but then have gone on to have worse migraines the last two years than ever in the previous 25.” This is one of those situations where it obviously doesn’t happen to everyone, say only 1-3 % of the time, but if its true for you, it could be 100% true for you. And that’s what this blog site is about: finding out what migraine root cause factors might be true for you, and then, what to do about them. This article is an extension of past “migraine and COVID” posts: FAQ Episode 56: Update on COVID spike protein levels and migraines and the more extensive FAQ Episode 38: COVID and Migraine: The Spike Protein, Long COVID and therapy options (for paid subscribers). If you think that either an illness from COVID or the SARS mRNA shot (and for some…both) has played a role in your headaches, I would review all three of these posts. This post is almost a “Part III” due to ongoing engagement with this issue in patients I’m seeing, even now at five years post the initial appearence of the COVID-19 virus.

Why was COVID different from most other viral illness?

While COVID-19 is a viral infection like many others we have experienced, it was distinct, especially in the early days, for producing a extraordinary degree of inflammation. This was true for both the acute phase, and can extend through months, or even years later. Having a headache during the acute phase of COVID-19 is reported in 50% or more of patients, and around one-third report persisting headache issues after COVID “recovery.”

I was still working part-time in the ER in 2020-2022, and we would draw a panel of inflammatory factors for COVID positive patients if they were being considered for hospital admission. They were off the charts! We had never seen such combinations of sky high levels for inflammatory markers like c-reactive protein, d-dimer and even cardiac markers like troponin, in patients with respiratory viral infections. In light of that, I would like to review for you:

-why such a strong inflammatory response was present with COVID-19

-how post COVID infection can make migraine headaches worse

-how to assess it, and what you can do about it

Why COVID is so pro-inflammatory, and how does COVID related pathology make migraines worse?

A good part of this is due to the “spike protein” imbedded in the surface of the COVID virus. This protein allows these viruses to penetrate host cells and promote viral replication. This spike protein can also cause damage to the vessels forming the blood brain barrier (BBB). This, along with misdirected immune responses, have been identified as a major cause of chronic neurological symptoms in post COVID inflammatory conditions1 (for more on BBB inflammation, ‘leaky brain’, and migraine see FAQ Episode 86: A damaged blood-brain barrier in migraine: who has it, how to manage it) That's why post-COVID “brain fog” and headache are such common complaints. When the spike protein is produced in excess over time (via either illness or vaccine), it can:

-inflame the blood vessels of the brain. In one study2 looking at post COVID cerebral hemorrhage events, spike protein expression was detected in 43.8 % of COVID vaccinated patients, predominantly localized to the intima of cerebral arteries, and persisting for many months post-vaccination. This was most often seen in the female patients in the study.

-potentially stimuate CGRP pain receptors, as this receptor and the spike protein share some structural mimicry allowing a degree of cross-reactivity.

-cause mitochondrial dysfunction. As migraine is for many, if not most individuals a disorder marked by bioenergetic deficit, this can be a significant root cause provocative factor.

-provoke maladaptive immune responses, which can be pro-inflammatory. A related and notable finding3 showed that markedly elevated levels of full-length spike protein were detected in the plasma of individuals with post COVID-19 vaccine myocarditis, whereas no excess free spike protein was detected in asymptomatic vaccinated control subjects. Immune mediated inflammation in a major organ invites dysfunction, be it inadequate cardiac output in the heart, or overstimulation of the trigeminovascular pathway in the brain, resulting in a migraine.

Of course, these factors will overlap with any other pro-inflammatory conditions an individual may have. Those with “severe or fatal outcomes” with acute COVID infections had the following associated comorbid conditions, all of which had their own pro-inflammatory contributions: Obesity 42% of the time, Hypertension 40%, Diabetes 17%, Cardiovascular disease 13%, Respiratory disease 8%, Cerebrovascular disease 6% or a malignancy 4%. We saw this routinely in the ER setting, where you could almost predict who would end up in the ICU by how many overlapping comorbid problems (especially those top three) they had going on. If you have any one or more of them, a COVID (via illness or vaccine) induced event could make you more prone to migraines, or headaches in general.

Assessing your levels of spike protein damage

While your symptom complex alone may be evidence enough to pursue therapy of “spikology” related inflammation, it may be helpful to quantify the amount of spike protein activity you currently have on board. Most labs can quantify your antibody levels for SARs (COVID-19) spike protein, which is a reasonable proxy for potential spike induced inflammation. At Labcorp, for instance, you or your doctor would ask for test #164090 “SARS-CoV-2 Semi-Quantitative Total Antibody, Spike.” They consider a “high level” to be 2500 U/ml. Some labs don’t even report it higher than this (they just say >2500). The Labcorb test quantifies this level up to 25,000 U/ml. Its interesting that many experts consider a SARS-CoV-2 antibody level >0.8 U/ml to be a protective response. I have seen levels of 15,000 plus in my symptomatic migraine patients. So, is a response of 2500 U/ml, which is 3,125 times higher than the protective threshhold a good thing? How about 15,000 U/ml? That’s 18,750 times that threshold. Still a good thing? As a proportional analogy, an ounce of cool water is refreshing. But 146 gallons? Somewhere between those two volumes is called drowning. What’s the optimal level for ‘protection’ that is still safe from overkill side effects? The real answer is: nobody knows for sure. But when we see post-COVID inflammatory driven side effects, especially migraine, its probably safe to say that reducing spike protein levels could be helpful.

If you have excess anti-spike protein antibody, it will typically drop over time. When the spike protein level drops, the antibody levels will also drop within 1-2 years. However, some people who had the mRNA COVID injection can continue to produce spike protein over time. Right now this extended presence of spike protein has been documented to be up to 2 1/2 years after injection, and and as we monitor it over time, it could turn out to be even longer. In this case, an intact immune system might document high antibody levels that reflect this. If you have documented elevated spike antibody levels, you may want to monitor them over time.

Clearing spike protein and its inflammatory effects

There is a lot of good information online on how to clear excess spike protein related to post COVID or SARs mRNA shot and related “long haul” symptoms. A great resource is the Independant Medical Alliance’s I-Recover protocol.

I’ve used a variation of this the last few years. Its hard to do everything that is recommended, so I’ll triage these interventions within three major categories:

Lifestyle factors:

-intermittent daily fasting (such as eating only between noon and 6 PM) or a full day fast (say, once a week.) Fasting stimulates the removal (autophagy) of spike protein and related misfolded proteins induced by the spike protein. Autophagy can play a critical role in reversing the “spikopathy” induced by COVID infection. There is evidence that ivermectin, along with intermittent fasting, can act synergistically to clear spike protein. See more on ivermectin dosing below.

-healthy sun exposure, aiming for 30 minutes of mid-day sun 3-4 times a week, if possible.

-moderate physical activity. On one hand, patients with this situation typically have limits on the intensity of activity they can tolerate. On the other, whatever you choose, everyday ask yourself “what am I going to do today to move?” Start by staying within limits that don’t worsen your symptoms. Check your heart rate, and start by keeping the max at exercise’s end at or under the 105-110 bpm range. Walking, yoga, water aerobics, tai chi or light resistance training are all entry-level options.

-if you have migraines, strongly consider not taking additional COVID-19 booster injections. Almost goes without saying, but some ‘authorities’ are still routinely promoting them for everyone. Older adults with multiple comorbidities are, as a group, one example of where the innoculation might reduce serious net morbidity or mortality. I don’t think that includes many readers here.

Nutritional cofactors as therapy (in my general version of importance):

-bromelain: can break down the spike protein. It helps to take this once or twice a day on an empty stomach to maximize it being absorbed intact. Look for a dose of 500 mg (containing 2,400 GDU per gram digestive units/cap) to take twice daily.

-ECGC: this extract from green tea can effectively bind the SARS-CoV-2 spike protein. Typical products are in the 275-500 mg size, with a target dose of ~400-800 mg/day. They should be in “standardized extract” form, and decaffeinated. Because EGCG can interfere with the metabolism of folate, which is essential for fetal growth and development, you should not take EGCG supplements if you are pregnant.

-nattokinase: This highly effective fibrinolytic and antiplatelet agent targets the abnormal clotting that can occur from spike protein-related disease. Dosage: 2000 F.U. (fibrin units, also labeled as ‘200 mg’ on some labels) twice daily for 90 days, once daily thereafter. Some good brands include ‘Doctor’s Best’, NutriCost and Swanson’s.

-Vitamins D and K2: optimize your Vitamin D level to 60-80 ng/ml (‘normal’ = 30-100 most labs) along with at least 100 mcg Vit K2/day.

-curcumin 500 mg twice daily. Look for a product where that total is measured as “95% curcuminoids.” The liposomal version is also a good choice. Curcumin is an excellent non-drug anti-inflammatory agent.

-melatonin: A powerful regulator of mitochondrial function, melatonin has anti-inflammatory and antioxidant properties. Should be taken at least an hour prior to bedtime. Usually 3-5 mg is a good place to start, and up to 10 mg if you don’t have excess drowsiness the next A.M.

-resveratrol or a combination flavonoid: is a plant flavonoid with antiviral, anti-inflammatory, anticoagulant, and antioxidant properties. Resveratrol also binds to spike protein which helps to activate the autophagy process.⁷Because resveratrol potentiates the effect of intermittent fasting in activating autophagy it is best taken during fasting (between meals), and not directly with food.

For the purposes of this discussion, it would be taken in a dose of 500 mg twice daily. If, for instance, you were only eating between noon and 7 PM, you might take one dose in the AM on arising and the other at bedtime. For maintenance therapy, once daily at 500 mg would be sufficient.

One of my favorite versions of this nutrient includes the flavonoid quercetin, which acts synergistically with resveratrol and also increases it’s bioavailability. It also assists in blocking viral replication, making it one of my favorite go-to supplements during virus outbreaks. Make sure that you get at least 30 mg of daily zinc with it if taken to potentiate this specific benefit.

The products I have taken and recommend for this combination are:

1) Purely Beneficial brand Resveratrol. Because the oral bioavailability of resveratrol is typically low, I prefer the bio-enhanced formulation containing trans-resveratrol from Japanese Knotweed Root, which has a much better absorption. This product has 605 mg of this trans-resveratrol per cap, along with a well balanced polyphenol mix to potentiate its benefit.

2) Jarrow Formulas Quercetin 500 mg. One dose daily would be a good complement to the resveratrol. If experiencing pandemic type viral exposure, the dose can be twice daily, along with the zinc as mentioned above.

Prescription options

-ivermectin: Ivermectin binds to the spike protein to assist in its elimination. Ivermectin also has potent anti-inflammatory properties. Safe and effective dosages are in the 0.4 mg/kg/day range (12-13 mg twice daily for someone ~150 lbs) I’ve had patients use this for two week intervals in any given month at a time. Check with your physician and the compounding pharmacist for individualized instructions.

-biologics to block CGRP effects. As there may be cross-reactivity between CGRP receptors and spike protein, blocking or modulating the CGRP messenger molecule or its receptors with medications like Aimovig, Ajovy, Emgality, Vyepti, Ubrelvy, Nurtec, Qulipta or Zavzpret may be helpful if persistant or elevated spike protein involvement is suspected. See FAQ Episode 26: Your response to the latest migraine drugs vs. the root causes of your headaches for more information on this, or discuss it further with your prescribing physician.

Be your own best advocate, but also…find your tribe

If you have post COVID onset or worsening of migraines you may likely have to buck the system to get your needs met. The conventional medicine community is just starting to recognize and admit that the COVID mRNA shots were: 1) not for everyone and 2) carried more risk and less benefit than “as originally advertised.” Still, you may get some resistance to getting a lab order for spike protein antibody, or for getting a prescription for ivermectin. Fortunately, many states are going to “OTC” (non-rx) status for ivermectin, and even if you don’t have lab proof of elevated spike levels, the interventions noted above can still be initiated safely. If you find a nearby compounding pharmacy, they typically can identify the local “front-line doctors” who are likely to be versed in these protocols. See FAQ Episode 78: Finding a local integrative minded doc for more on this.

I wish ‘the system’ was set up to offer individualized integrative therapy for migraine (or any other health concern), delivered where you are and at a price we all could afford. In the meantime, you can move forward by identifying the members of your team, and find the allies, locally and online, that will support you and offer additional insights into effectively managing your migraines.

Good luck on your journey! If you maintain a strong sense of curiosity and an obstinate level of persistance, you will find answers!

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