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Stress is an unavoidable part of life, and while it often carries a negative connotation, it is actually a fundamental survival mechanism. When faced with a perceived threat, whether physical or emotional, the body instinctively reacts to protect itself. This automatic response is commonly known as the "fight, flight, or freeze" response. While it serves an essential function in dangerous situations, chronic activation of this response due to daily stressors can have significant consequences for mental and physical health.
The body’s response to stress is rooted in human evolution. When our ancestors encountered a predator, their nervous systems immediately prepared them to either confront the threat (fight), escape to safety (flight), or become still and unnoticed (freeze). While modern-day stressors may not include wild animals, our nervous system reacts similarly to job pressures, financial worries, or social conflicts.
According to the Cleveland Clinic, stress is the body's response to change, activating a physiological reaction that helps us adapt and protect ourselves. While short-term stress can be beneficial, prolonged exposure can lead to an overactive stress response, negatively impacting overall well-being.
The fight response prepares the body for direct action. When triggered, the nervous system releases adrenaline, increasing heart rate, blood pressure, and muscle tension. While this reaction once helped early humans fend off predators, today it manifests as irritability, frustration, or aggression.
For instance, the employee who has experienced too much workload may work extremely long hours just to succeed. In short term, the action may produce good results but mostly ends in burnout, anxiety, and physical illness, for example, tension headache or digestion problems.
The flight response triggers an intense need to remove oneself from a stressful situation. Just as our ancestors would flee from danger, modern individuals may avoid conflict, quit jobs impulsively, or detach from relationships when overwhelmed.
Flight mode is linked with restlessness and anxiety. Individuals may have a sense of needing to get up and go-pacing, changing environments constantly, or avoiding tasks that seem too overwhelming. Someone with a flight response might have the desire to change jobs constantly, relocate constantly, or become reclusive in order to avoid perceived dangers.
The freeze response occurs when the nervous system perceives a threat as too overwhelming to fight or flee. Rather than taking action, individuals shut down, feeling numb, disconnected, or paralyzed by fear.
Unlike fight or flight, which involve heightened activation, freeze mode slows down physiological functions. A person experiencing freeze mode may feel physically unable to move, struggle to make decisions, or find themselves dissociating from their emotions. This can manifest in situations such as public speaking anxiety, where someone might "blank out" or feel stuck in the moment.
When faced with a stressor, the autonomic nervous system (ANS) activates, triggering physiological changes, including:
For those experiencing the freeze response, the body undergoes a different reaction, often reducing heart rate and causing physical immobility rather than heightened activation.
While the stress response is necessary for survival, frequent activation due to daily stressors can take a toll on health. Recognizing your default response—whether fight, flight, or freeze—can help in developing effective coping mechanisms.
If possible, changing your environment can help signal to your brain that the threat has passed. Stepping outside for fresh air, finding a quiet place, or distancing yourself from overwhelming stimuli can help regulate emotions.
Deep, slow breathing can be used to counteract the stress response by engaging the parasympathetic nervous system, which promotes relaxation. Techniques such as diaphragmatic breathing or the 4-7-8 method (inhale for four seconds, hold for seven, exhale for eight) can be particularly effective in calming the body.
This helps release pent-up energy and aids in the endorphin cascade, natural boosters for our mood.
Relieving oneself from stress can come in many ways, but sharing it with trusted friends, a family member, or a good therapist will sure give that psychological boost of hope. Social support is an especially effective way of cushioning people against the stressors that they are subjected to in chronic forms.
While occasional stress is normal, chronic activation of the fight, flight, or freeze response can indicate underlying mental health concerns, such as anxiety disorders or post-traumatic stress disorder (PTSD). If stress is affecting daily life—leading to sleep disturbances, difficulty concentrating, or persistent feelings of fear—it may be time to consult a mental health professional.
Credit: Susan Kroll
NBC News producer Susan Kroll, 58, initially attributed her occasional difficulty remembering words to menopause-related brain fog. However, tests revealed an elevated genetic risk of Alzheimer’s disease and abnormal amyloid levels in her brain.
Her journey began when she sought a diagnosis for her mother, who had started experiencing memory problems at 75. While helping her mother, Kroll decided to investigate her own risk after learning that Alzheimer’s risk can be genetic, she wrote on Today.com.
Testing showed that Kroll’s mother carried two copies of a gene called APOE4. Everyone inherits one APOE gene from each parent. The three common variants are APOE2, which may reduce Alzheimer’s risk; APOE3, the most common variant, which has a neutral effect; and APOE4, which increases the risk.
According to the Mayo Clinic, people with two copies of APOE4 are eight to 12 times more likely to develop Alzheimer’s.
To understand her own risk, Kroll took a cheek-swab genetic test in October 2024.
"I had an APOE4 and APOE3 gene, making me two to three times more likely to develop Alzheimer’s. I was a bit relieved," Kroll wrote.
Also read: Normal Ageing or Alzheimer's? Doctors Explain Six Key Differences to Watch For
In May 2025, Kroll took a blood test developed to help diagnose Alzheimer’s disease, which had recently been cleared by the US Food and Drug Administration (FDA).
The test measures certain proteins, including a specific form of tau, that can indicate the presence of amyloid plaques in the brain. These protein deposits are considered a hallmark of Alzheimer’s disease.
Kroll said her "results were well outside the normal range". She had also noticed occasional difficulty remembering words, which she had initially attributed to menopause-related brain fog.
She was given personalised recommendations covering diet, exercise, supplements and sleep.
Kroll made several changes to her daily routine.
"I cut out artificial sweeteners and limited fried and processed foods, red meat, cheese, sweets and alcohol. Every day, I started eating leafy greens, whole grains, veggies and fruit, and every week multiple servings of fish, walnuts, almonds, avocado and berries."
She also intensified her workouts, doing 45–60 minutes of cardio three to four days a week, alongside strength training. She focused on three muscle groups, completing three sets of each exercise with eight to 10 repetitions. She also started going to bed earlier.
Read More: India Gets Its First Alzheimer’s Drug: Know All About Eli Lilly’s Lormalzi
In December 2025, Kroll began treatment with Kisunla, an anti-amyloid infusion approved by the FDA in 2024.
A previous brain scan had shown elevated amyloid levels in every quadrant of her brain. Clinical trials have shown that Kisunla can slow cognitive and functional decline in eligible patients.
After six infusions, Kroll underwent another brain scan in May 2026 to assess her progress.
Her amyloid score dropped from 86 to four. The radiologist noted, "The amyloid issue has resolved."
Further blood tests showed that her tau levels were normal. Kroll suggested that her dietary changes may have contributed to this result.
Kroll currently has neither Alzheimer’s disease nor mild cognitive impairment. However, she continues to have positive biomarkers and an elevated genetic risk. She believes the "early interventions helped slow down or potentially stop the progression of changes years before they could worsen".
Her journey is far from over. She continues to receive care at the Alzheimer’s Prevention Clinic, where her blood and biomarkers are monitored monthly.
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Obesity drugs such as semaglutide and tirzepatide may offer benefits beyond weight loss and blood sugar control. Researchers say these medicines could also help protect brain function, including memory and other cognitive abilities.
Researchers from the University of Gothenburg and the University of Copenhagen examined evidence on how these drugs affect the brain and their potential to inform treatments aimed at preserving cognitive function. The review was published in the journal Science.
Semaglutide and tirzepatide belong to a class of medicines that act on metabolic pathways involved in appetite and blood sugar regulation. They may also influence biological processes important for brain function.
Animal studies suggest that GLP-1 drugs can affect learning and memory. However, findings from human studies have been mixed.
Studies analysing patient records have linked GLP-1 treatment to a lower risk of dementia among people with type 2 diabetes. However, these findings do not establish whether the medicines themselves are responsible for the reduced risk.
The potential benefits of these drugs have also been examined in people with Alzheimer's disease.
In Novo Nordisk's EVOKE and EVOKE+ clinical trials, semaglutide did not slow disease progression in patients with early Alzheimer's disease, despite producing changes in several biological markers associated with the condition.
However, researchers say these findings do not rule out potential benefits in other groups of patients.
People with obesity or type 2 diabetes may experience difficulties with attention, planning and processing speed. These cognitive problems are often associated with metabolic and vascular health, making them potential targets for treatment.
Stina Börchers, first author of the review and a researcher affiliated with the University of Gothenburg and the University of Copenhagen, said it is important to establish whether these treatments can help preserve cognitive abilities, particularly when started before problems become established.
“We need to find out whether these treatments can help people with obesity or diabetes preserve their cognitive abilities, particularly if treatment begins before cognitive problems become established,” Börchers said.
Researchers are trying to understand whether the potential effects of obesity medicines on the brain result from improved metabolism, direct action on the brain, or a combination of both.
Christoffer Clemmensen, senior author of the review and research group leader at the University of Copenhagen, said advances in obesity medicines offer new opportunities to understand how metabolic regulation influences brain function.
“By disentangling the direct and indirect effects of these drugs on the brain, we may ultimately be able to develop treatments specifically aimed at preserving cognitive function,” Clemmensen said.
The researchers are calling for clinical trials that assess memory and other cognitive abilities from the beginning of treatment.
They also stress the need to monitor older and frail patients. Rapid weight loss and loss of muscle mass could affect physical function and potentially reduce the benefits of treatment in these groups.
For now, whether obesity drugs can help preserve cognitive function remains an important research question. More clinical evidence is needed before they can be considered treatments for protecting brain health.
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For 25-year-old Kaela Knight, a nail artist from Colorado, taking tirzepatide, the active ingredient in Eli Lilly's Mounjaro and Zepbound, brought an unusual side effect: skin so sensitive that even a light touch hurt.
Knight started treatment in September 2024 at 210 pounds and eventually reached 125 pounds. But during her second month, as her dose increased from 2.5 mg to 5 mg, she began experiencing burning sensations.
"I always describe it as feeling like a sunburn without any visible redness or irritation," she told the Daily Mail.
The sensation affected her hips, forearms and neck. Episodes lasted 24–48 hours, although some persisted for about a week.
Other patients taking Novo Nordisk's Ozempic and also Mounjaro have reported similar experiences.
Known as allodynia, this nerve-pain condition makes normally harmless sensations, such as clothing brushing against the skin or a light touch, painful. Patients describe it as a sunburn without visible redness or irritation.
Although it is not an established side effect of Ozempic, Wegovy, Mounjaro or Zepbound, medical reports have documented similar symptoms. A direct link remains unproven.
"I have [areas] all over that are burning. It's driving me nuts," one Reddit user wrote. Another said painkillers and lidocaine gels offered little relief.
Some patients report improvement after reducing their dose or stopping treatment.
Also read: Ozempic Hair: GLP-1 Drug Use Linked To 7% Higher Baldness Risk In Men
Semaglutide, used in Ozempic and Wegovy, mimics the GLP-1 hormone. Tirzepatide, used in Mounjaro and Zepbound, targets GLP-1 and GIP receptors.
Dr Richard Siegel, an endocrinologist at Tufts Medicine, told the Daily Mail that these drugs could potentially affect nerve signalling through the brain and spinal cord.
Another theory involves changes in the fat layer beneath the skin during weight loss, which could affect nerve sensitivity. Neither explanation has been proven.
An October 2025 report documented two cases:
Some patients report improvement over time or after reducing their dose.
Dr Siegel said symptoms can last days to weeks, potentially becoming less noticeable as the body adjusts to treatment, much like nausea and constipation.
"It's possible something similar is happening here, where temporary changes in receptor activity alter nerve signaling at first, but become less noticeable as the body adjusts," he said.
Read More: Stopping Ozempic, Wegovy, Mounjaro Linked To 22% Higher Heart Attack, Stroke Risk: Study
Clinical trials have also recorded dysesthesia, a broader category of abnormal sensations, including burning and tingling. It is not necessarily the same as allodynia.
In a high-dose oral semaglutide trial, dysesthesia occurred in fewer than 3% of 334 participants, compared with none receiving placebo.
Phase 3 trials of retatrutide, an experimental drug targeting GLP-1, GIP and glucagon receptors, reported:
Risk factors remain unclear. Dr Siegel believes higher doses could play a role.
"As best as I can tell, it would mostly be people on higher doses of these medications," he said.
He also suggested that people with greater pain sensitivity, including those with fibromyalgia, might be more susceptible.
Patients experiencing unusual skin burning or sensitivity should consult their doctor. Dose adjustments or alternative treatments may be considered, but medication should not be changed or stopped without medical advice.
Allodynia can also occur with shingles, migraines and nerve damage, so symptoms should not automatically be attributed to weight-loss drugs.
Dr Siegel recommends recording when symptoms occur, where they appear and what makes them better or worse.
Persistent or worsening pain should be medically evaluated.
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