How Insulin Resistance Impacts the Brain and What We Can Do About It
Insulin resistance and hyperinsulinemia adversely affect cognitive health, as evident in Alzheimer's patients. There are viable solutions.
The adverse effects of insulin resistance on the brain are clear now. New-generation scientists started seeing neurodegenerative disorders like Alzheimer’s disease as metabolic disorders for valid reasons.
In those patients, they observed common metabolic abnormalities like impaired glucose metabolism, insulin resistance, oxidative stress, chronic inflammation, and mitochondrial dysfunction.
The pivotal point of these factors is insulin resistance. Insulin is a hormone that regulates blood glucose, the brain's primary energy source. Insulin resistance is a common feature of metabolic disorders, impairing insulin signaling in the brain via various mechanisms I will discuss.
As I will explain in this article, insulin resistance can affect the brain, causing impaired glucose metabolism, oxidative stress, mitochondrial dysfunction, and chronic inflammation. There is significant evidence in the literature on the adverse effects of insulin resistance on the brain.
As highlighted in this paper, “The key intersection among diabetes, obesity, and dementia is insulin resistance, which has been classically described to occur in peripheral tissues in diabetes and obesity and has recently been shown to develop in Alzheimer’s disease brains.”
This 2018 review published in Nature informs that “both type II diabetes and Alzheimer’s disease are associated with brain insulin resistance and brain dysfunction.”
This paper in Molecular Neurobiology informs that “Recent studies are now beginning to recognize type 2 diabetes mellitus, characterized by chronic hyperglycemia and insulin resistance, as a risk factor for Alzheimer’s disease and other cognitive disorders.”
I structured the article into three sections. First, I will introduce the three critical factors affecting insulin resistance in the brain. Then I will provide tips to check insulin resistance and make the body more insulin sensitive.
3 Critical Impacts of Insulin Resistance on the Brain
1 — Impaired Glucose Metabolism
Insulin resistance in the brain can impair glucose uptake and utilization, contributing to neuronal dysfunction and cognitive impairment. Impaired glucose metabolism is explained with the concept of hypometabolism.
“Hypometabolism, characterized by decreased brain glucose consumption, is a common feature of neurodegenerative diseases. Initial hypometabolic brain state, created by characteristic risk factors, may predispose the brain to acquired epilepsy and sporadic Alzheimer’s and Parkinson’s diseases.”
The brain requires a constant supply of glucose to produce energy. The brain cannot produce enough energy to function properly when glucose metabolism is impaired unless it has alternative energy like ketones.
Impaired glucose metabolism can cause a reduced ability of brain cells to produce energy, leading to cognitive impairment and a lack of other brain functions, as evident in patients with neurodegenerative disorders like dementia.
Impaired glucose metabolism can damage blood vessels in the brain, causing reduced blood flow and oxygen to the brain. This situation might damage brain cells and impair cognitive function.
Vascular damage can lead to the development of cerebrovascular diseases (stroke, carotid stenosis, vertebral stenosis, intracranial stenosis, aneurysms) and neurodegenerative disorders like Alzheimer’s disease.
According to this paper, “growing evidence supports the concept that Alzheimer’s disease is fundamentally a metabolic disease with substantial and progressive derangements in brain glucose utilization and responsiveness to insulin and insulin-like growth factor stimulation.”
The paper informs that “impairments in energy metabolism, increased oxidative stress, inflammation, insulin and IGF resistance, and insulin/IGF deficiency in the brain should be incorporated into all equations used to develop diagnostic and therapeutic approaches to Alzheimer’s disease.”
Impaired glucose metabolism can increase oxidative stress and inflammation in the brain, which I cover in the following sections.
2 — Oxidative Stress and Mitochondrial Damage
Insulin resistance can lead to increased oxidative stress in the brain, contributing to neuronal damage and cognitive decline. This oxidative stress can damage neurons (brain cells) and connective tissues.
Insulin resistance can cause oxidative stress by causing mitochondrial dysfunction, inflammation, lipid peroxidation, and impaired antioxidant defense mechanisms.
Mitochondria are the primary site of energy production in cells and neurons. When they are impaired, they can produce excess reactive oxygen species, which can cause oxidative stress.
This 2021 study concluded, “Normal insulin signaling is important for mitochondrial functioning. Brain insulin resistance contributes to obesity and may play an important role in neurodegeneration.”
Insulin resistance can cause increased lipid peroxidation, contributing to oxidative stress. Lipid peroxidation happens when free radicals attack lipids (fat molecules) in cell membranes, causing damage and producing more reactive oxygen species.
Insulin resistance can impair the body’s antioxidant defense mechanisms, increasing oxidative stress. Antioxidants are molecules that can neutralize reactive oxygen species and prevent oxidative damage.
Insulin resistance can reduce glutathione levels and impair their ability to neutralize reactive oxygen species, leading to synaptic pathology.
This paper states, “An increasing body of evidence indicates a deficient or altered energy metabolism that could change the overall oxidative microenvironment for neurons during the pathogenesis and progression of Alzheimer's disease, leading to alterations in mitochondrial enzymes and glucose metabolism in brain tissues.
This 2021 paper concludes, “Oxidative stress associated with insulin resistance also dysregulates glycogen synthase kinase, leading to increased tau phosphorylation. Insulin-degrading enzymes metabolize both insulin and amyloid β-protein. Defects in this enzyme are the basis for a strong association between type II diabetes and Alzheimer’s disease.”
This 2015 review informs, “The most important processes in aging-associated conditions, including neurodegeneration, include insulin, insulin growth factor 1 signaling, the mTOR, and sirtuin. These longevity pathways involve metabolism, cognition, stress response, and brain plasticity.”
Oxidative stress through insulin resistance can also damage the beta cells in the pancreas that produce insulin, leading to a vicious cycle of further insulin resistance and oxidative stress.
3 — Chronic Inflammation in the Brain
By increasing oxidative stress, insulin resistance in the brain can also increase inflammation, contributing to neuronal damage and cognitive impairment.
Insulin resistance can contribute to chronic inflammation in the brain by activating inflammatory signaling pathways in response to high levels of insulin in the blood. These pathways can release pro-inflammatory cytokines and the activation of immune cells in the brain.
This 2021 review informs that “neurodegenerative diseases show cognitive decline and memory loss, which accompany increased systemic inflammation, the ‘inflamm-aging,’ and the insulin resistance.”
Insulin resistance can disrupt the blood-brain barrier. The blood-brain barrier is a specialized layer of cells regulating the movement of molecules into and out of the brain.
More specifically, insulin resistance can lead to the breakdown of the blood-brain barrier, allowing pro-inflammatory cytokines and other immune cells to enter the brain and contribute to chronic inflammation.
According to this paper, “Studies have identified overlapping neurodegenerative mechanisms, including oxidative stress, mitochondrial dysfunction, and inflammation that are observed in obese, typeII diabetes, and Alzheimer’s patients.”
The paper states, “Advanced glycation end products generated by chronic hyperglycemia and their receptor RAGE provide critical links between diabetes and Alzheimer's disease.”
Glycation is a chemical reaction that occurs when sugars bind to proteins or lipids without controlling enzymes, forming advanced glycation end products. In the brain, glycation can occur in neurons, glial cells, and blood vessels, negatively affecting brain function and health.
Glycation in the brain can contribute to the development of neurodegenerative diseases by forming toxic aggregates that can damage neurons and cause inflammation.
Advanced glycation can also contribute to the development of cerebrovascular disease by causing damage to the blood vessels in the brain. This can reduce blood flow to the brain, which can cause cognitive impairment and other neurological disorders.
Since hyperinsulinemia and insulin resistance contribute to Alzheimer’s disease progressions by promoting inflammation in the peripheral system, the researchers of this 2022 paper in Frontiers hypothesized that “hyperinsulinemia might affect microglia, which plays a crucial role in the neuroinflammation of Alzheimer’s disease.”
How do we know we are insulin resistant?
The most apparent symptom of an insulin-resistant body is the growing midsection, even when a person eats less and exercises more.
Excessive visceral fat accumulation is a good indicator. However, there might be some exceptions. Therefore, proper checks with help from healthcare professionals can provide more definitive results.
In addition to the various tests I mentioned below, family doctors or specialists check physical signs, symptoms, medical history, and family history to diagnose insulin resistance.
Physicians can order various glucose tests to detect insulin resistance, metabolic syndrome, prediabetes, and type II diabetes.
Some common ones are fasting plasma glucose, glycated hemoglobin A1c, random plasma glucose, glucose challenge, and oral glucose tolerance tests.
There are also specific tests to diagnose insulin resistance and sensitivity. The procedures are complex and comprehensive, requiring specialist intervention, as documented in this book chapter on the NIH site by medical doctors.
As documented in this paper high triglycerides to HDL-cholesterol ratio is associated with insulin resistance in normal-weight healthy adults. Thus, getting checked for lipids, especially for hyperlipidemia, can provide valuable information on this condition.
As high insulin levels can trigger the growth of skin cells, they might lead to dark spots in the neck, arms, or groin called “acanthosis nigricans.” This condition is one of the symptoms of insulin resistance and hyperinsulinemia.
There are also genetic causes of insulin resistance that require specialists to diagnose. The known genetic conditions are inherited lipodystrophy, myotonic dystrophy, Werner syndrome, and Alstrom syndrome.
How can we make our cells more insulin sensitive?
I have written numerous articles on making the body more insulin sensitive and fat-adapted. Making our cells insulin-sensitive can also make the neurons insulin-sensitive. Instead of repeating the details, I’d like to provide key points here.
Regular exercise is the most effective way to make the body insulin sensitive, especially two hours after meals. Both cardio and resistance training is good for making our muscle cells insulin sensitive. Besides, exercise can put the brain in growth mode by increasing BDNF.
The key mechanisms of exercise for insulin sensitivity are to burn glucose in the bloodstream, lower insulin secretion, and activate cells to take more glucose from the bloodstream and glycogen stores.
As glucose mainly comes from carbohydrates, lowering food with carbs, especially refined carbs full of sugar, is an excellent measure. The best approach is to get calories and nutrients from whole foods.
So, a good option is to arrange macronutrients by lowering carbs and increasing healthy fats with moderate bioavailable proteins to get adequate calories, essential amino acids, vitamins, and minerals.
This regimen is close to a ketogenic diet as fats and proteins impact insulin release less than carbs and create an alternative energy called ketosis.
Ketone bodies are an excellent energy source for brain function, lowering inflammation and increasing BDNF. By entering ketosis, we can clear the garbage from cells by activating autophagy and mitophagy.
Some people prefer frequent meals for various reasons. However, each time we eat, the body releases insulin to lower the glucose from the bloodstream. Therefore, if possible, cutting snacks can be helpful.
Related to meal frequencies, time-restricted eating is one of the most effective ways of making our cells more insulin sensitive.
Some people skip one meal, like breakfast, and others, like me, eat only one meal daily. I also perform long-term fasting occasionally to make my body more insulin sensitive.
As stress is a critical factor in insulin resistance, restorative sleep, rest, and timely recovery, which can lower the cortisol hormone, are crucial. Elevated cortisol can lead to insulin resistance.
Healthy weight management is key to insulin sensitivity. Insulin resistance is more common in overweight and obese people.
So if you are overweight, you may consider losing visceral fat by gradually lowering your caloric intake without compromising your essential nutrients, moving your body joyfully, and getting nightly restorative sleep which can balance your hormones.
Lowering alcohol consumption, stopping smoking, refraining from recreational drugs, and avoiding toxins can put the body in a metabolically advantageous position.
Regularly checking blood sugar and adjusting your calories accordingly can help prevent excessive blood sugar from causing too much insulin secretion. Obtaining professional support is necessary if you have metabolic disorders and hormonal dysfunction.
Conclusions and Takeaways
Studies clearly indicate that insulin resistance can negatively affect the brain via impaired glucose metabolism, oxidative stress, chronic inflammation, and mitochondrial dysregulation.
Awareness of and understanding these mechanisms is important to adjust our lifestyle to prevent insulin resistance leading to neurodegenerative disorders like dementia.
Understanding these mechanisms is also important for healthcare professionals to develop new therapeutic approaches to prevent and treat cognitive decline and impairment.
Ancient wisdom saw the tight connection between body and mind. Modern science neglected the mind for a while. But new generation scientists now pay more attention to it. Holistic health principles encourage us to have healthy lifestyle habits by looking after our bodies and minds.
Chronic stress, which is one of the root causes of metabolic disorders, is the manifestation of an imbalance of our bodies and minds, as evident in the dysfunction of our hormones like insulin and cortisol.
Honoring the body's and mind's fundamental needs is vital to make our cells insulin-sensitive. In addition, we must monitor blood glucose proactively, take personal responsibility, and seek professional support when needed.
Thank you for reading my perspectives. I wish you a healthy and happy life.
As a new reader, please check my holistic health and well-being stories reflecting my reviews, observations, and decades of experiments optimizing my hormones and neurotransmitters.
ALS, Metabolic Syndrome, Type II Diabetes, Fatty Liver Disease, Heart Disease, Strokes, Obesity, Liver Cancer, Autoimmune Disorders, Homocysteine, Lungs Health, Pancreas Health, Kidneys Health, NCDs, Infectious Diseases, Brain Health, Dementia, Depression, Brain Atrophy, Neonatal Disorders, Skin Health, Dental Health, Bone Health, Leaky Gut, Leaky Brain, Brain Fog, Chronic Inflammation, Insulin Resistance, Elevated Cortisol, Leptin Resistance, Anabolic Resistance, Cholesterol, High Triglycerides, Metabolic Disorders, Gastrointestinal Disorders, Thyroid Disorders, Anemia, Dysautonomia, cardiac output, and urinary track disorders.
I also wrote about valuable nutrients. Here are the links for easy access:
Lutein/Zeaxanthin, Phosphatidylserine, Boron, Urolithin, taurine, citrulline malate, biotin, lithium orotate, alpha-lipoic acid, n-acetyl-cysteine, acetyl-l-carnitine, CoQ10, PQQ, NADH, TMG, creatine, choline, digestive enzymes, magnesium, zinc, hydrolyzed collagen, nootropics, pure nicotine, activated charcoal, Vitamin B12, Vitamin B1, Vitamin D, Vitamin K2, Omega-3 Fatty Acids, N-Acetyl L-Tyrosine, and other nutrients.
I publish my lifestyle, health, and well-being stories on EUPHORIA. My focus is on cellular, mitochondrial, metabolic, and mental health. Here is my collection of Insightful Life Lessons from Personal Stories.
Disclaimer: My posts do not include professional or health advice. I only document my reviews, observations, experience, and perspectives to provide information and create awareness.
You might join my six publications on Medium as a writer by sending a request via this link. 22K writers contribute to my publications. You might find more information about my professional background. You may join Medium with my referral link to enjoy unlimited content.
