GLP-1 meds and weight loss vs migraines
Frequently Asked Questions Episode 93
It’s everywhere. TV ads, social media posts and prescribed for at least three people you know.** This “drug class of the decade” augments the effect of glucagon-like peptide-1, a natural hormone that plays a role in regulating blood sugar and appetite. These drugs are “GLP-1 receptor agonists”, often called GLP-1 drugs. Some of the most common versions include:
Dulaglutide (Trulicity)
Semaglutide (Ozempic, Wegovy or Rybelsus).
Tirzepatide (Mounjaro, Zepbound)
The impact of this drug class may make them the most revolutionary pharmaceutical innovation of the 2020’s. To my knowledge, thus far there have been no major studies looking at their impact on migraine headaches. However, I have had several migraine patients report back on the pros and cons of their GLP-1 therapy, and I’d like to use that as a base for considering how the judicious use of these medications may affect users who also have migraine headaches.
**if that stat applies to you, consider forwarding or restacking this post for them.
Before we do, please contribute to this poll as it applies to you:
How do these drugs work?
GLP-1 drugs work by mimicking the natural hormone GLP-1, which plays a key role in regulating blood sugar and appetite. By binding to GLP-1 receptors in the brain, pancreas, and gut, they:
stimulate insulin release, which increases effective calorie burning
reduce glucose production in the liver, which keeps the body from compensating for the reduction of sugar calories in the diet
slow down gastric emptying, which leads to a feeling of fullness and reducing the desire to eat. This slowed digestion helps to prevent blood sugar spikes and keeps blood sugar levels more stable throughout the day
allow your decreased hunger to more effectively pare down the total number of calories eaten per day, helping to improve blood sugar control and manage weight
contribute to the upregulation of the ketogenic pathway, with an increased production of ketone bodies from fat stores. Most organs and tissues can use ketone bodies as an alternative source of energy. Notably, the brain uses them as a major source of energy during periods where glucose is not readily available. This helps make the relative fasting effect of these medications tolerable.
If you combine these factors at the right pace, along with lifestyle and habit changes, you can favor the burning of visceral fat, lower average blood sugar levels and preserve lean body mass for both long-term health and short-to- intermediate term cosmetic benefits.
Using GLP-1 agonist medications may allow for you to change lifestyle habits and ‘reset’ your some aspects of your glucose and lipid metabolism. The evidence shows, however, that unless you hold tight to these lifestyle changes (diet content, portion size, exercise and activity levels) that many if not most treated individuals will trend back toward some version of their initial metabolic status after phasing off this medication.
How can the GLP-1 drugs affect root cause factors in migraines?
I’ve seen no evidence that the GLP-1 agonist drugs themselves directly clear migraines, but here is a short list of how ancillary effects of this therapy that can influence migraine expression. See this post’s last section for related “Action Considerations.” These GLP-1 agonist effects include:
the reducion of visceral fat. This is primarily intra-abdominal fat that plumps out our midsection. For most of us this is the cosmetically unappealing fluffage, so good riddance, right? Visceral fat is also infamous for having a systemic pro-inflammatory effect. It produces cytokines like interleukin-6 and TNF-alpha, and also contributes angiotensin, which contricts blood vessels. Its not surprising that being overweight is a known aggravating factor for migraines. Over time, we would expect that the reduction of weight, especially the visceral fat contributors to migraine root cause factors (like inflammation and vascular instability—which promote migraines) would also reduce vascular headaches in those successfully using the GLP-1 meds. That seems to be the trend with my migraine patients using these medications. I’ll be watching emerging studies on this relationship with interest.
an exaggeration of either dehydration or hypoglycemia states. Both of these can precipitate a migraine event (also see FAQ Episode 72: Hydration and Headaches and FAQ Episode 67: Sweet cravings, hypoglycemia and migraines.) The reduction of both appetite and bowel motility reduce natural signals for us to stabilize baseline fluid and caloric levels. The reduction of craving “background noise” is a key to this therapy’s success, but also requires ongoing vigilance to avoid the dips in hydration or basal blood sugar that can trigger migraines for some people.
the promotion of ketosis. This could either stabilize or aggravate a migraine condition:
-on the one hand, ketosis can add another stable brain energy source. While glucose is the brain’s 7/24 “go to” energy source, it can run lean when you are in a semi-fasting state (i.e. like being on a GLP-1 med.) That’s when the body compensates with production of ketone bodies from the liver. This can give the brain an additional energy source that enhances mitochondrial function, buffers your reserves and stabilizes your migraine threshold.
-on the other, day to day alterations in carb intake could interrupt the ketosis process. This can induce swings in blood glucose and brain energy which can heighten the potential for hypoglycemia induced migraine episodes. If you are on a GLP-1 med and have periods of feeling listless and fatigued, with episodes of brain fog and mood swings, this situation might apply to you. I’ve found that taking a supplement with ketone support can minimize this rollercoaster effect.
the lipid load detox process: the pros and cons of “melting away excess fat”:
-our fat cells store more than fat. Potential toxins like herbicides, pesticides, heavy metals and volatile organic solvents are lipophilic, meaning that they readily bind to and can be stored in fat rich tissue. A relative fasting state, like that induced with the GLP-1 drugs, can ‘liquify’ your fat stores as those calories are used for cellular metabolism. Where do the toxins we had parked there go? Rapid weight loss can lead to an increase in some circulating toxin levels. Typically we clear these through the kidney, liver, GI tract and skin. Part of the fatigue, body aches and ‘brain fog’ complaints in the weight loss process can be due to an inadequate detoxification capacity as we shed fat stores. On the other hand, I’ve worked with migraine patients who successfully navigated through the weight loss and associated detoxification to see over time a definite improvement in headache frequency and intensity.
-unloading excess stores of linoleic acid. Linoleic acid (LA) is the most abundant of the omega-6 ‘seed oils’ that are a ubiquitous part of the American diet. When liberated from fat, LA can break down to lipid peroxides which inhibit mitochondial efficiency and promote inflammation. Both of these concerns are core root causes for migraine headaches. Most of us already have too much LA in our systems, and liberating it too quickly could promote your migraines.
Unloading organic chemicals, heavy metals or excess linoleic acid can all promote inflammation and degrade mitochondrial function. On the other hand, as they are depleted, you will have a cleaner and more efficient metabolic milieu. In the next section I’ll discuss how to limit the damage done during the fat liquification process which is promoted by the GLP-1 meds.
the potential to inhibit chronic pain sensitization pathways. The research on this is just emerging, but the GLP-1 meds seem to help manage addiction pathways in some patients, including those related to coping with chronic pain. This will be interesting to observe going forward, and future GLP-1 drug versions may be developed with more specific applications in this area. In the meantime, if the pain of chronic migraine might be moderated by this drug class, all the better. No promises, but we’ll take what we can get!
Action Considerations
If you choose to try one of the GLP-1 agonist medications, consider the following:
The best advice, without a doubt, is: start low and go slow! I know some people have just got to lose 40 lb by that class reunion/wedding/cruise to Jamaica, etc. in 4 months flat. That’s also the “got nauseated/fatigued beyond belief/constipated, had pancreatitis, and BTW check out my Ozempic face” crew. Don’t be them. They are also the ones whose migraines typically got worse with GLP-1 therapy. They went into ketosis too quickly, with some of the associated hypoglycemia and detox problems we discussed above. They also lost “structural fat” which we need in the face, chest, upper arms and buttocks to maintain functional and cosmetic integrity.
Stay active, and allow for slow but steady progression on your exercise intensity or duration. Include strength training to tone and maintain lean body mass. Excess muscle loss is one of the major pitfalls of rapid weight loss. And if you are past 40, regaining it can be a long and slow process. Pay special attention if exercising in an especially warm or humid environment, or if exercising at altitude (did you know the average elevation in Colorado is 6800’? Years ago I got a headache after running the ‘BOLDERBoulder’ 10K. While massaging my throbbing left temple as I recovered on the grass by the finish, I made the connection, and realized that nearby Denver was called “The Mile High City” for a reason.)
Whether male or female, if you are mid-40’s plus, consider checking and optimizing hormones, especially testosterone, before launching into a major weight loss plan.
include sufficient protein in your diet to preserve and tone your lean body mass. Aim for at least 1 gram of protein per kilogram of body weight per day. As protein gives a sense of satiety that will add to that of the medication, its best to divide your protein intake into several servings throughout the day.
do your best to keep carb intake evenly distributed through the day, especially avoiding taking too large a percent of your daily carbs in one sitting. This will help avoid reactive hypoglycemic events, and also allow your ketosis to have as steady a baseline as possible.
take measures to improve your detoxification capacity, including:
-increasing your level of hydration through the day, not just with exercise.
-encouraging bowel regularity. Sips of water on a regular basis will better tolerated than trying to take 8-12 oz at a sitting.
-taking daily magnesium citrate or glycinate to assist with bowel motility and regularity. Work up to 200-500 mg. per day, or as needed to achieve at least one bowel movement per day. This can also directly help reduce migraines (see FAQ Episode 83: Revisiting the vital role of magnesium in migraine management.)
-if available, add a sauna session 2-3 times per week. Be cautious to start easy, such as only 10-15 minutes/session to start.
-consider using natural toxin sequestrants like cilantro, chlorella and spirulina to assist with liver and bowel detox. Take with water or a meal and back off the dose if it affects your bowel transit (i.e. is constipating.)
safely clear excess stores of linoleic acids. This would include 1) avoiding LA rich processed food and other forms of seed oils (sunflower oil, safflower oil, corn oil, and soybean oil) and 2) increase omega-3 rich foods like fatty fish (salmon, mackerel), flax seeds, and walnuts. While mobilizing linoleic acid, you can reduce related inflammation by using carnosine rich protein sources, like beef, pork, chicken, turkey, tuna, salmon, sardines, dairy and green peas. There are few non-protein sources of carnosine, so vegans may benefit from taking carnosine as a supplement 500-1000 mg day, especially when dropping two or more pounds of fat per week.
consider a nutritional supplement that supports both nutritional bioenergetics as well as ketone bodies to ensure consistent brain energy and repair. My favorite, and really the only product that covers the nutritional and metabolic shortfalls unique to migraine, is Brain Ritual, which contains my favorite migraine nutrients as well as a d-Beta-Hydroxy-butyrate, the bio-identical match for the ketone bodies you make during the semi-fasting state. Taking this twice daily (as 1/2 dose every 12 hours) can be an excellent cross-cover for the nutritional and energy requirements for any migraine patient, especially when on a GLP-1 medication. See this Brain Ritual link for all the details and a $30 off offer for my readers.
By using these guidelines, I hope that those of you who are using a GLP-1 medication while also battling migraines can find your “threading the needle” pathway to success in rewiring your metabolism, weight loss and headache reduction.
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