Investigating GLP-1 Injections: Potential Mitochondrial Dysfunction in Non-Diabetic Patients Presenting with Migraines and Hypoglycemia: A Case Report

July 15, 2026 jbenson@innovisionhm.com Journal Article 0

Jana Jamail, CNS; Rachel Knowles, BS, MS, DCN, CNS, LDN; Leslie Fuller, BS, MS, ND

 

Abstract

Introduction • GLP-1 medications are widely used for weight loss in patients with and without type 2 diabetes. However, limited research exists on their effects in non-diabetic patients, particularly concerning mitochondrial function. This case report investigates the potential of altered mitochondrial dysfunction as a cause of side effects of GLP-1 medications in patients without type 2 diabetes.

Case Presentation • The patient, a 43-year-old female with a BMI of 32, presented with hypoglycemia and persistent migraines with auras after Ozempic and Mounjaro injections.

Outcomes • The patient changed her diet to include 90 grams of protein and frequent small meals throughout the day. She took CoQ10, D-ribose, vitamin B complex, and acetyl-l-carnitine, to address the migraines, and this also improved the mitochondrial function. The patient reported balanced blood sugar after changing her diet; her migraines improved and did not return after taking supplementation.

Conclusion • This case report emphasizes the need for awareness and monitoring of potential mitochondrial side effects from GLP-1 injections in patients without type 2 diabetes. Nutritional and supplemental interventions effectively managed the patient’s symptoms and emphasized the need for tailored interventions in patients using GLP-1 medications. Further research is needed to understand how GLP-1 injections impact mitochondrial function. (Integrative Medicine: A Clinicians Journl, 2024,23.6:21-25)

 

Jana Jamail, CNS, Certified Nutritional Consultant, Certified Plant-Based Nutrition, Certified Wellness Counseling. Human Nutrition and Functional Medicine Masters Alumnus, University of Western States, CEO and Founder of Rose+Ginger Nutrition, Austin, Texas, USA.  Rachel Knowles, BS, MS, DCN, CNS, LDN, Doctor of Clinical Nutrition, Licensed Dietitian Nutritionist, Certified Nutrition Specialist, Board Certified in Holistic Nutrition. Adjunct Professor in Human Nutrition and Functional Medicine, University of Western States Founder of Seedling Nutrition, Moorseville, NC, USA.  Leslie Fuller, BS, MS, ND, Naturopathic Physician. Professor in Doctorate of Chiropractic and Human Nutrition and Functional Medicine University of Western States Portland, OR, USA.

 

Corresponding author: Jana Jamail, CNS

E-mail: jana.r.jamail@gmail.com   

 

 

Introduction 

Glucagon-Like Peptide-1 (GLP-1) medications have dramatically increased in popularity as weight loss drugs for patients with and without type 2 diabetes. Semaglutide GLP-1 use has increased since 2022, with over 9 million prescriptions written.1 Patients without diabetes are also utilizing these drugs for weight loss when diet and exercise prove ineffective.1 Semaglutide, Ozempic, and Mounjaro are GLP-1 mimics that decrease blood glucose levels, change gastric emptying time, reduce cravings, and increase satiety.2-4 GLP-1 medications are prescribed as a once-weekly subcutaneous injection of 2.4-3.0 mg, depending on symptoms.2-4

GLP-1 injections were originally used to improve the health of patients with type 2 diabetes. These patients have altered mitochondrial function from decreased insulin sensitivity, and GLP-1 agonists can improve and restore mitochondrial function.5-9 GLP-1 agonists’ impact on metabolic and mitochondrial function has been studied extensively in patients with type 2 diabetes, demonstrating improvements in blood glucose levels, insulin sensitivity, pancreatic beta cell function, and mitochondrial function through mitochondrial uncoupling.5-9 In non-diabetic patients with obesity, GLP-1 agonists improve mitochondrial respiration, mitogenesis, and inflammation, and increase the number of mitochondria in adipose tissue, but there is limited research on how GLP-1 affects mitochondria in other tissues in this patient population.10

Undesirable side effects can accompany GLP-1 medications, and as many as 84% of patients may experience gastrointestinal disorders such as diarrhea, nausea, vomiting, unpleasant burps, gastroesophageal reflux disease (GERD), and peptic ulcers.11,12 In non-diabetic patients, hypoglycemia and headache have been reported in up to 10-21% of patients after taking GLP-1.13 Hypoglycemia could indicate altered mitochondrial function from medically reduced glucagon levels.14 The mechanism and cause of headache were not examined, and migraines were not mentioned.13 Migraines are not commonly reported as a side effect of GLP-1 medications, and an animal study has shown that liraglutide GLP-1 injections can improve migraine symptoms by increasing IL-10 levels.15,16 Migraine pathogenesis could be attributed to altered mitochondrial function in neurons from GLP-1 agonists, however, this topic is underexplored.

Non-diabetic patients taking GLP-1 injections may infrequently experience side effects such as migraines and hypoglycemia, which could indicate altered mitochondrial function in pancreatic alpha and neuron cells. This case explores the potential mechanisms behind migraines-associated headaches as a side effect in non-diabetic patients taking GLP-1 injections for weight loss, with a focus on alteration in mitochondrial function.

 

Case Narrative

A 43-year-old female with a body mass index (BMI) of 32, fasting blood glucose of 80 mg/dL, and HbA1c% of 5.2 indicating obesity and non-diabetes, sought nutritional and supplemental support from a nutritionist to increase her energy and address the side effects from her Ozempic prescription, including nausea and hypoglycemia. The patient’s past medical history was significant for weight gain following pregnancy and occasional migraines with aura. She was taking Lexapro, Synthroid, Gabapentin, and Pantoprazole for acid reflux, and had followed a vegan and vegetarian diet for 16 years.

The patient was prescribed 0.5 mg of Ozempic by her physician in April 2023. After the patient reported adverse side effects of chronic nausea and hypoglycemia her Ozempic dose was decreased to 0.25 mg. Her physician recommended her to wear a glucose monitor in the evenings to wake her if her blood glucose became dangerously low. The patient reported suboptimal protein intake and eating infrequent meals throughout the day due to her job on a dietary recall form.

After six months, in October 2023, the patient’s physician changed to 0.15 mg of Mounjaro to mitigate her chronic nausea. In January 2024, three months after taking 0.15 mg of Mounjaro, the patient reported regular migraine occurrence, and shoulder, hip, and body pain. The migraine symptoms included dizziness, scalp pain, auras, vision changes, misremembering words, and pain on the left side of her head. The patient has had infrequent aura migraines beginning in 2018 but experienced new migraine symptoms after Mounjaro injections.

 

Table 1. Timeline of patient’s nutrition interventions

  Intervention Rationale
04/2023 90 grams of lean protein daily. 20-30 grams of protein at dinner. Frequent small meals eaten throughout the day Improve hypoglycemia.16-17
01/2024 Methylated vitamin B complex once per day Increase absorption of vitamin B12 and improve migraines.13
300 mg CoQ10 once per day with high fiber meal Improve migraines.16,18-19
500 mg Acetyl-L-carnitine once per day
4250 mg D-ribose once per day with a high fiber meal Improve fatigue.20

 

Diagnostic Assessment

The patient was diagnosed with hypoglycemia and recommended to wear a continuous glucose monitor. The nutritionist identified suboptimal protein intake based on the patient’s dietary recall form. Further, the form indicated infrequent meals and ingesting high glycemic foods. No imaging or workup was done for the migraine presentation.

 

Therapeutic Intervention

In April 2023, the nutritionist recommended a diet with 90 grams of protein daily to improve hypoglycemia.17 The nutritionist recommended small frequent meals throughout the day and the removal of high glycemic processed foods to maintain her blood glucose levels.18 In January 2024, regular migraine occurrence was noted by the patient, this was the first speculation that the GLP-1 medication could alter mitochondrial function, rather than being triggered by hypoglycemia. The nutritionist recommended 300 mg of CoQ10 per day, 4250 mg of D-ribose per day, vitamin B complex once per day, and 500 mg of acetyl-L-carnitine per day to address the migraines.19-22 The patient reported nausea as an adverse side effect of acetyl-L-carnitine and discontinued the supplement after two weeks.

 

Outcomes

In April 2023, two weeks after the patient changed her diet to include 90 grams of protein per day and eating regularly throughout the day her, blood glucose levels stabilized as evidenced by the cessation of the glucose monitor waking her during the night. After two weeks she no longer needed to wear the blood glucose monitor. Hypoglycemia was addressed through protein and regular meals.9,10,23 The patient continued the diet after changing to Mounjaro in October 2023. In January 2024, the patient began taking CoQ10, D-ribose, and vitamin B complex and reported her migraine symptoms had gone away within 48 hours of starting the supplements. The patient continued taking CoQ10, D-ribose, and vitamin B complex and her migraine symptoms did not return.

 

Discussion        

The discussion below delineates the potential role of altered mitochondrial function in the onset of migraine headaches in patients taking GLP-1 injections. Migraines and hypoglycemia are possible indicators of increased mitochondrial ATP synthesis and signaling in pancreatic alpha cells and neurons.

 

Mitochondrial Function

The patient’s side effects may be associated with altered mitochondrial function, specifically regarding the pancreatic alpha mitochondria and activity rate in the neuronal electron transport chain.

 

Hypoglycemia

GLP-1 medications decrease blood glucose, and the patient reported hypoglycemia while taking Ozempic but not Mounjaro.2 The patient reported having hypoglycemia at night and wore a glucose monitor to wake her up if her glucose levels dropped too low. Her glucose monitor woke her up three times. When she implemented the high-protein diet her monitor no longer woke her to indicate dangerously low glucose levels.

GLP-1 agonists inhibit glucagon from the alpha cells in the pancreas, which is essential for maintaining blood glucose levels by signaling the liver to convert glycogen through glycogenolysis and into the bloodstream to increase glucose levels and maintain blood sugar.5,7 GLP-1 agonists may inhibit the signal from alpha cell mitochondria to release glucagon and therefore increase the risk of hypoglycemia because the body cannot naturally stabilize blood sugar levels.5,7 This could increase the risk of hypoglycemia in non-diabetic patients with healthy blood sugar levels, as the patient in this case report did, but this is speculative.8 In a clinical trial on obese patients taking varying doses of semaglutide and liraglutide, patients who took 0.3-0.4 mg of GLP-1 medications with and without fasting reported the highest amount of headaches and hypoglycemia.13 The dose of GLP-1 medications could be a factor for both symptoms.13 Practitioners may need to consider prescribing a lower dose in non-diabetic patients with normal blood glucose levels to reduce the potential risk of hypoglycemia.13 Fasting also exacerbated hypoglycemia, and ingesting enough calories is essential for supporting this patient population.13 Research needs to be done to understand how GLP-1 medications affect pancreatic alpha cells in non-diabetic individuals to better support patients taking the drug.

 

Dietary Interventions

Before treatment, this patient followed a vegan and vegetarian diet for 16 years. She did not prioritize protein, which could have contributed to the severity of her hypoglycemic symptoms from Ozempic. She also did not eat regularly throughout the day and sometimes relied on ultra-processed snack foods between meetings.17 Patients who ate four meals per day three to four hours apart saw a decrease in hypoglycemic symptoms, especially when the diet included nutrient-dense whole foods, although these patients were not taking GLP-1 medications.17 Since decreasing blood sugar is one of the main mechanisms of GLP-1 agonists, hypoglycemia was a concern for this patient. Eating 90 grams of protein daily is essential for maintaining blood sugar levels because protein increases glucagon and stabilizes blood sugar.17,18 The patient saw significant improvement in her hypoglycemia when she consistently ate throughout the day and when she ingested 20-30 grams of protein in the evenings from beans, tofu, turkey, fish, and eggs.

 

Speculated Migraine Triggers

Hypoglycemia can contribute to migraines; however, hypoglycemia was addressed, and migraines still occurred. Under the influence of Exendin-4, another GLP-1 agonist medication from Gila monster saliva, mitochondria operate differently.23 Protons leak across the mitochondrial membrane into the matrix, and this diverts energy from the electron transport chain to heat production; this process is called mitochondrial uncoupling (Figure 1).24 Exendin-4 acts as an uncoupling agent which changes the metabolic rate and increases resting energy expenditure.23 Exendin-4 also affects sirtuin enzymes, which regulate mitochondrial function, metabolism, and inflammation, and when increased from mitochondrial uncoupling, can potentially lead to migraines.23 Ozempic and Mounjaro may also influence mitochondrial uncoupling in non-diabetic patients, which could increase the rate of ATP synthesis and contribute to migraines. However, more research needs to be done to determine how the GLP-1 agonists dissociate ATP synthesis in this patient population.

 

Figure 1. Mitochondria uncoupling from GLP-1

 

When observed during functional imaging, the medulla and hypothalamus are activated during migraine attacks.24 As GLP-1 receptors are also found in the medulla and hypothalamus, these cells may have altered mitochondrial function following the use of GLP-1 medications.24 GLP-1 receptors in the medulla and hypothalamus could receive too much GLP-1 hormone from Mounjaro injections, and ATP synthesis activity could increase from mitochondrial uncoupling, resulting in unbalanced reactive oxygen species.25 A cross-sectional study showed an increased rate of mitochondrial ATP synthesis leads to increased levels of reactive oxygen species, resulting in impaired mitochondrial function and the release of peptides hypoxia-inducible factor-1α, fibroblast growth factor-21, calcitonin gene-related peptide, and pituitary adenylate cyclase-activating peptide-38 which can trigger migraines.25 GLP-1 agonists could be causing mitochondrial uncoupling in the receptors in the medulla and hypothalamus in non-diabetic patients, which may increase ATP synthesis and migraines, but this is speculative.9,17,26 Migraines are not commonly reported from GLP-1 agonists, however, another case report included a patient presenting with hemiplegic migraines for over 60 days following GLP-1 injections.16 The case report did not mention mitochondrial function.16

Vitamin B2, CoQ10, and D-ribose are essential for mitochondrial function, particularly in the electron transport chain complexes one, two, and three (Figure 2).19,20,27 CoQ10 is an antioxidant and decreases oxidative stress by rebalancing oxidation in the mitochondria.20 When the patient presented with regularly occurring migraine symptoms after changing medications, this was the first indication that GLP-1 injections could influence changes to mitochondrial activity in neurons, and micronutrient intervention may be necessary to support the electron transport chain. In an animal study, GLP-1 medications altered cholesterol metabolism and reduced cholesterol levels by reducing HMG-CoA reductase and SREBP-1C enzymes.26 HMG-CoA reductase stimulates the synthesis of CoQ10, and if inhibited, CoQ10 levels drop, and energy production is disrupted as CoQ10 is required to initiate the electron transport chain.23 If CoQ10 cannot be used for the electron transport chain and the rate of ATP synthesis increases from GLP-1 injections; this could alter mitochondrial function, and increase levels of reactive oxygen species, oxidative stress, and release peptides that could trigger migraines.20,24,26 D-ribose can improve ATP synthesis and cellular processing when the rate of the electron transport chain is altered or if there are missing enzymes that inhibit energy production.27 D-ribose can bypass enzymatic pathways in the mitochondria and still generate ATP, which can improve mitochondrial function.27

 

Figure 2. Micronutrients for electron transport chain

 

In this case study, the patient experienced relief from migraines after taking CoQ10, vitamin B complex, and D-ribose supplementation while on Mounjaro.18,20,22 GLP-1 -induced alterations to mitochondrial and electron transport function, may have been resolved through supplementation. It is possible that Mounjaro impacted mitochondrial function, ultimately creating a deficit of CoQ10, and contributing to migraine occurrence. Upon CoQ10 supplementation, the energy balances and alterations in mitochondrial function were restored. Human studies need to be conducted to understand how GLP-1 medications interact with mitochondria in the medulla and hypothalamus and with HMG-CoA reductase.


Conclusion

The patient lost 40 pounds after one year of taking Ozempic and Mounjaro, resulting in a BMI of 25.8, and is no longer categorized as obese. She changed her diet to include 90 grams of protein, took the recommended supplements, and found these nutraceutical interventions were the most effective in alleviating medication-related migraine symptoms and hypoglycemia. Non-diabetic individuals with normal blood glucose levels may be at a greater risk of hypoglycemia and migraines from GLP-1 medications because of the speculated changes to mitochondrial function and the rate of ATP synthesis. Future research should explore the effects of GLP-1 agonists on mitochondrial function in neuronal and alpha pancreatic cells through in vitro and in vivo studies. Screening patients for migraine status may be necessary to evaluate the increased risk to benefit of prescribing GLP-1 medications.

 

Patient Perspective

The patient noted that while the high-protein diet was beneficial, the supplements that addressed her migraine symptoms were the most impactful. She appreciated targeted treatments based on her symptoms from Ozempic and Mounjaro.

 

Limitations

The patient submitted her diet through a form which increases the risk of reporting bias.

 

Author Disclosure Statement

There were no conflicts of interest in the making of this case study.

Acknowledgement

The authors thank the patient for their informed consent in using their case information for this case report.

Funding

No funding was received for the writing of this case study.

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