There are more than 150 types of headaches, which are broadly classified into two main categories: primary and secondary headaches. Secondary headaches arise from underlying medical conditions such as sinusitis, head injury, intracranial hemorrhage, brain tumors, or hypertension. In contrast, primary headaches—including migraine, cluster headache, and tension-type headache—represent the most common causes of discomfort and reduced quality of life worldwide (Wang et al., 2023). Advances in functional neuroimaging, genetics, and neurophysiology have demonstrated that cortical hyperexcitability, brain dysfunction, neural sensitization, and neurodegeneration play critical roles in the pathophysiology of primary headache disorders (Wang et al., 2023).
For both primary and secondary headaches, the immediate cause of pain is often associated with disruptions in neural activity or damage to the nervous system within the brain or head (Bouchier et al., 2023; Hong et al., 2017; Wang et al., 2023). Neuronal damage manifests in various forms, including neuronal degeneration, demyelination, axonal injury, and cell death. These alterations disrupt signal transmission, leading to symptoms such as muscle weakness, numbness, cognitive impairment, or motor dysfunction.
Role of glucose in neural activity
Disruptions in energy metabolism are common factors affecting brain function in general and neurotransmission in particular (Harris et al., 2012; Mergenthaler et al., 2013).
Although energy can be derived from proteins and lipids, the mammalian brain relies primarily on glucose as its main energy source (Mergenthaler et al., 2013). Insufficient energy supply may lead to damage to synapses (Harris et al., 2012). In adults, the brain accounts for approximately 2% of body weight but consumes about 20% of total glucose-derived energy. Most of this energy is used for synaptic activity, with gray matter consuming significantly more energy than white matter. Glucose utilization increases further during brain activation (Mergenthaler et al., 2013). In cases of headache caused by energy deficiency, glucose supplementation can rapidly alleviate symptoms.
Beyond its role as an energy substrate, glucose metabolism also provides essential precursors for maintaining neuronal and glial cells and for synthesizing neurotransmitters (Mergenthaler et al., 2013). It also plays a role in regulating programmed cell death. Notably, hexokinase II (HKII) inhibits apoptosis in many cell types; however, under glucose deprivation, it may promote neuronal cell death. Neuronal depolarization—associated with brain injury and intracranial hemorrhage—has been shown to be mitigated under hyperglycemic conditions (Mergenthaler et al., 2013; Taş et al., 2019).
In short, disruptions such as neurotransmitter depletion, large-scale neuron loss, or loss of membrane potential can all impair brain function and trigger headaches—yet may be partially relieved by restoring glucose supply.
Figure 1. Glucose (Glc) as the Primary Energy Source for the Mammalian Brain
(a) Specialized brain centers detect central and peripheral glucose concentrations and regulate glucose metabolism as well as neuroendocrine signaling via the vagus nerve.
(b) Glucose delivery to the brain is regulated by neurovascular coupling. Glucose enters the brain from the blood by crossing the blood–brain barrier via the glucose transporter GLUT1, and
(c) other metabolites (e.g., lactate) can also be utilized.
(d) Glucose provides energy for neurotransmission, and
(e) several glucose-metabolizing enzymes regulate cell survival. Disturbances in glucose metabolism at any of these levels may lead to various brain disorders [4].
Effects of free radicals on neural activity
Free radicals are highly reactive chemical species capable of inducing damage to various cellular components. They are generated as byproducts of oxidative processes occurring within cells, including electron transport for ATP production and the dissociation of oxyhemoglobin for oxygen delivery (Webb, 2011).
The brain is the most energy-demanding organ in the human body. According to Mergenthaler et al. (2013), it consumes glucose at a rate approximately ten times higher than the average of other organs, with even greater utilization during periods of increased neuronal activity. Consequently, the production of free radicals in the brain is substantial. Structurally, the brain contains up to 50% lipids by dry weight (Fantini & Yahi, 2015), and cholesterol is a critical component of the myelin sheath that insulates nerve fibers and facilitates rapid impulse conduction (Saher & Stumpf, 2015). However, lipids are inherently susceptible to oxidative attack, rendering the brain particularly vulnerable to free radical–induced damage (Clemens & Panetta, 1995).
Free radicals have been implicated in both the etiology and pathogenesis of numerous central nervous system disorders, including neuritis, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, brain aging, cerebrovascular atherosclerosis, and epilepsy (Rokyta et al., 1996).
Under conditions such as prolonged mental exertion, sleep deprivation, or excessive cognitive load, headaches may arise as a result of intensified oxidative damage to brain components. If sustained, this process can lead to more severe and potentially irreversible neurological injury. Therefore, reducing brain activity to a resting state is a primary strategy to limit free radical generation. In addition, the provision of antioxidants represents an effective approach to protect the brain and mitigate oxidative damage. Hydrophilic antioxidants (e.g., vitamin C, polyphenols) exert rapid effects following administration, whereas lipophilic antioxidants (e.g., vitamins A and E, carotenoids) reach target tissues with a longer delay (Rokyta et al., 1996).
The role of oxygen in neural and immune function
Oxygen is indispensable for energy metabolism. Oxygen deficiency disrupts energy production and can lead to widespread neuronal cell death (Mergenthaler et al., 2013). Clinically, hypoxia is associated with symptoms such as dizziness, severe headache, fatigue, nausea, confusion, and loss of consciousness.
In addition to its role in energy production, oxygen contributes to neuroregeneration, immune function, phagocytosis, and the clearance of oxidatively damaged cells. Nitric oxide (NO·), a signaling molecule produced by endothelial cells and macrophages, plays a crucial role in neurotransmission and regulates multiple physiological processes, including memory, sleep, appetite, anxiety, reproduction, and cerebral blood flow (Garthwaite, 2018). Its production depends on oxygen availability (Thomas, 2015). NO also helps neutralize free radicals, thereby limiting oxidative damage.
Increased oxygen supply—through deep breathing or physical activity—not only enhances energy metabolism but also promotes endogenous antioxidant defenses and immune responses.
Conclusion
Headaches are manifestations of disrupted neural activity or impaired neural transmission, which may result from energy deficiency or neural damage within the nervous system. Dysfunction caused by energy deficiency can be rapidly corrected, whereas neural damage always leads to prolonged functional impairment and requires more time to recover. Nevertheless, symptoms can be alleviated by the following measures:
- Glucose supplementation: Providing glucose to the brain rapidly resolves headaches caused by energy deficiency and may reduce the severity of secondary headaches by mitigating neuronal damage (reducing neuronal cell death and membrane depolarization).
- Deep breathing to increase oxygen supply: Enhanced oxygen supply helps eliminate free radicals, a common cause of neuronal injury, and accelerates immune-mediated tissue repair.
- Rest and mental relaxation: Allowing the brain to rest is essential to reducing headaches caused by both energy deficiency and oxidative neural damage.
Because the brain consumes large amounts of energy and produces significant levels of free radicals, continued activity under energy-deficient or damaged conditions may exacerbate neural injury and headache symptoms.
Fresh fruits as an effective remedy for headaches
Fresh fruits contain abundant natural sugars, vitamins, and antioxidants. They provide rapidly absorbable glucose for the brain to address energy deficiency while simultaneously supplying antioxidants that help prevent and reduce neural damage caused by free radicals. Consuming fresh fruits combined with deep breathing and adequate rest may help relieve headaches quickly and effectively.
Although deep breathing may be an effective method for removing free radicals and promoting tissue repair, it may have limited effectiveness in headaches caused by energy deficiency and may be less effective in individuals suffering from malnutrition or general weakness.
According to anecdotal experiences, consuming sugar solutions may help relieve headaches, neuralgia, and fever. Some individuals report that dissolving several teaspoons of cane sugar (commonly brown sugar) in hot water, sometimes with lemon juice, can quickly alleviate headaches. The author has also personally experienced relief from headaches after drinking a cup of black bean sweet soup and noticed that post-alcohol fatigue and headaches disappeared only after eating a small portion of rice.
Notes and Considerations
Under glucose-deficient conditions, lipid oxidation and autophagy are activated to compensate for energy demands (Asadollahi et al., 2024). Lipid oxidation can supply approximately 20% of the brain’s energy (Panov et al., 2014). Notably, in a resting state without active neuronal firing, fatty acid metabolism may help prevent severe ATP depletion and irreversible axonal damage. This may explain why individuals in calm states can tolerate fasting better than those under stress.
Although oxidative stress is a recognized mechanism in neurological diseases, many antioxidant-based therapeutic approaches have shown limited success in clinical settings (Asadollahi et al., 2024). Thus, while antioxidants and fruit consumption may help prevent or mitigate neural damage, they are not sufficient for reversing established neurological injury.
Finally, chronic excessive sugar intake may lead to serious metabolic disorders such as diabetes and obesity (Jacques et al., 2019). Therefore, while fruit consumption may help alleviate headache symptoms, it should not replace proper medical treatment for underlying conditions, nor should sugar be overused as a symptomatic remedy.
Ngo Duy Sa
Faculty of Food Science and Technology
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