How sugar may damage the brain

Most people have heard that sugar is unhealthy, but how exactly can it work against your good mental health?

When you eat concentrated sources of rapidly-digestible carbohydrates such as sugar, flour, fruit juice, and processed cereal products, your blood sugar (glucose) can rise sharply, triggering an equally strong rise in the hormone insulin in an effort to bring blood glucose back down to normal.1

These dramatic fluctuations in glucose occur inside the brain as well, because brain glucose seems to typically rise and fall in proportion to blood glucose.2

These steep increases and drops in glucose and insulin levels could potentially negatively affect your brain and body chemistry in three critical ways.

Refined carbohydrates can destabilize hormones and mood

The problem with unstable insulin levels is that insulin isn’t simply a blood sugar regulator; it also acts as a signaling hormone that affects numerous other hormones throughout the body. Every time insulin rises and falls, these hormones may follow suit, which can place you on a hormonal rollercoaster.3

Let’s say you start off your morning with a food rich in refined carbohydrates — like orange juice, a bagel, or a bowl of corn flakes. Within a half hour, your blood sugar escalates, and your pancreas immediately releases insulin into your bloodstream to pull the extra sugar (glucose) out of your blood and squirrel it away into your cells. About an hour or so later, as your blood sugar is dropping, you may feel tired, unfocused, and hungry.4

The body perceives rapidly falling glucose as a potential emergency, so it releases a mixture of hormones to keep glucose from falling below normal. This mixture includes the stress hormones cortisol and adrenaline — our “fight-or-flight” hormone.5

Many people consume refined carbohydrates at every meal and as snacks, which can place their hormones on a seesaw all day long and even well into the night. Age, metabolism, gender, genetics, and activity level can influence what your personal hormonal rollercoaster feels like.6 Fluctuating energy levels, difficulty concentrating, mood swings, binge eating, irritability, anxiety attacks, and insomnia are all possibilities, depending on the individual.7

Yet even if you aren’t aware of any symptoms on the outside, trouble may be brewing on the inside, as normal rhythms are disrupted in ways that can slowly, silently lead to health problems down the road. For more information, including graphs of sugar and hormone rollercoasters on different diets, read “Stabilize your mood with food.

Selection of bad sources carbohydrates

Refined carbohydrates can promote oxidation and inflammation

Unnaturally high blood sugar may promote oxidation and inflammation, which are features of many chronic diseases, including psychiatric disorders.8

What is oxidation?

The chemical reactions our cells rely upon to turn food into energy require oxygen molecules that can break apart into reactive “free radicals” during digestion. Free radicals are like little bulls in a china shop — left unchecked, they bump into and react with neighboring structures and DNA, potentially damaging cells from the inside out (oxidation).9

Since some amount of oxidation is normal and necessary, Mother Nature has armed us with a variety of our very own internal antioxidants to mop up excess free radicals. Under normal circumstances, these built-in antioxidants are sufficient to keep oxidation and anti-oxidation forces in balance and prevent cellular damage.10

The problem with high-sugar foods and beverages is that they can present chemical pathways with too much glucose at once, generating more free radicals than our internal antioxidants can neutralize.11 Depression, bipolar disorder, schizophrenia and obsessive-compulsive disorder are all potentially associated with excess oxidation.12

We are often told that the solution to our oxidation problem is to consume colorful, antioxidant-rich fruits and vegetables to bring our systems back into balance. Yet most plant antioxidants, when consumed in their natural form, are poorly absorbed by the human body, and it’s still unclear whether or not they are of much use to us.13

On the other hand, refined carbohydrates may deplete our natural antioxidants, making it appear as if we need more antioxidant power than we already have. Instead of buying antioxidants, wouldn’t it make a lot more sense to simply stop eating pro-oxidants? For more information about the pros and cons of antioxidants, including “superfood” examples, read the “The antioxidant myth.

What is inflammation?

Our immune system reacts to oxidative damage by mounting an inflammatory response. This isn’t the kind of inflammation that makes your brain swollen, red, or sore — it’s inflammation on a microscopic level. Multiple lines of evidence point to a connection between inflammation and many cases of depression, bipolar disorder, and schizophrenia.14

When cells are in distress, they release tiny cries for help in the form of “inflammatory cytokines” such as IL-6 and TNF-alpha that can be measured in the blood. Levels of these molecules are often higher in people with mood and psychotic disorders.15

Inflammatory cytokines may trigger damage to nearby brain cells and cause chemical imbalances in the brain by disrupting normal production of serotonin, dopamine, and glutamate — key neurotransmitters involved in psychiatric disorders.16While we don’t yet have clinical studies cementing a causal relationship, paths leading from sugar to oxidation to inflammation may help to connect the dots between modern diets and mental illnesses.

Mechanistic theories suggest that refined vegetable and seed oils like soybean and sunflower oil might also contribute to excess inflammation. However, this is controversial as a systematic review of randomized trials found no evidence that linoleic acid, the main omega-6 fatty acid in vegetable oils, increases inflammation, at least in healthy people.17 These  oils are found in all kinds of processed foods — from high-carbohydrate foods like chips and baked goods to popular low-carb foods like mayonnaise and salad dressings.

Omega-6 fatty acids are responsible for mounting the inflammatory response to oxidative damage, injuries and infections, whereas omega-3 fatty acids are responsible for initiating the healing response.18

These two forces likely work best when they are roughly in balance. Unfortunately, modern diets are not only extremely high in omega-6 fatty acids, they are also often low in omega-3 fatty acids compared to our hunger-gatherer predecessors.19 Imbalances in these essential fatty acids have been seen in many psychiatric disorders.20

Numerous studies have tested whether anti-inflammatory drugs can be used to treat mood and psychotic disorders — and they do sometimes help to some extent.21 But rather than taking drugs to simply mask symptoms — drugs which cost money and can cause side effects — why not start by eliminating processed foods instead?

Vegetable oils

Vegetable oils: What we know and what we don’t

GuideVegetable oils have quickly become a major source of calories in our food supply. Is that a good thing? To find out, let’s review what we know, and what we don’t know.

Too much sugar contributes to insulin resistance

Insulin resistance is emerging as a potentially important factor in the development of most of the mental health problems we fear — from straightforward conditions such as depression to complex brain degeneration disorders like schizophrenia and Alzheimer’s disease.22 As tragic as this may seem, understanding that insulin resistance strongly influences our risk for psychiatric disorders is tremendously empowering, because insulin resistance is a familiar beast we already know how to tame.

High-sugar diets may place too much pressure on the pancreas to produce high amounts of insulin to keep blood glucose under control. Over time, if exposed to elevated insulin levels too often, the receptors that transmit insulin’s instructions can become damaged and dwindle in number, making it increasingly difficult for cells to respond to insulin’s important messages.23

In people with insulin resistance, the insulin receptors responsible for escorting insulin from the bloodstream into the brain’s interior can malfunction and shrink in number, restricting insulin flow into the brain.24 If you have insulin resistance or type 2 diabetes, glucose may continue to easily enter the brain, but insulin will struggle to gain access.25

Without adequate insulin, brain cells can’t process glucose properly, and will start to slow down. This sluggish glucose processing problem is called “cerebral glucose hypometabolism” and is a key feature of many brain disorders, particularly Alzheimer’s disease.26

How low-carbohydrate diets can improve brain metabolism

If high blood sugar and insulin can jeopardize brain health through inflammation, oxidation, and insulin resistance, then we can hypothesize that reducing blood glucose and insulin levels could help improve brain health. A growing body of scientific literature supports the idea that ketogenic diets have the potential to address all of these underlying biochemical disturbances, and therefore hold great promise for the dietary treatment of psychiatric disorders.27

Carbohydrates tend to raise glucose and insulin levels the most, whereas fats raise them the least.28 So it stands to reason that a low-carb, high-fat diet could be one of the best ways to target these root causes of brain malfunction, improve brain metabolism, and protect the brain from further damage.

It has been known for nearly a century that ketogenic diets have the power to completely eliminate seizures in some children with epilepsy and significantly reduce the frequency of seizures in others.29 Although the exact mechanism is not know, the findings certainly suggest that low-carbohydrate diets can beneficially impact brain chemistry.

The brain is a highly-active organ that demands a constant supply of high-quality fuel. And while it’s true that some of its fuel must be in the form of glucose, that glucose does not need to come from carbohydrates in the diet.

The US Food and Nutrition Board acknowledges that “the lower limit of dietary carbohydrate compatible with life is apparently zero, provided that adequate amounts of protein and fat are consumed.”30 Through a natural process called “gluconeogenesis” (making glucose from scratch), the liver can make glucose and release it into the bloodstream for any cells that require it, including brain cells.31

When carb intake is reduced, insulin levels decrease. If  insulin levels are sufficiently low, your body switches from primarily burning sugar to primarily burning fat. This shift is called ketosis, in which your liver releases fat-like compounds called ketones into the blood to provide fuel for your cells. You can test to see if you are generating ketones with a blood ketone meter.

Although muscle cells and most other cells in the body can use fatty acids for energy, brain cells aren’t equipped to use them.32 So, they use ketones instead. Ketones are an excellent fuel source for the brain. They seem to burn more efficiently than glucose, producing less oxidation and inflammation.33

Although some rapid-fire brain cells always require some glucose (because it burns faster than ketones do), ketones can meet up to a remarkable two-thirds of the brain’s total energy requirements.34 In fact, some data suggests most brain cells will burn ketones over glucose, making ketones the preferred energy source for large portions of the human brain.35

Although insulin resistance of the brain makes it difficult for insulin to cross into the brain, it doesn’t interfere with the flow of ketones.36 Therefore, the more ketones you have in your blood, the higher your brain ketone levels will be, and the more ketones your brain cells can absorb and use for energy.37 As an added bonus, it just so happens that ketones burn beautifully in a low-insulin environment, making ketones an ideal fuel source for the insulin-resistant brain.

The food-mood connection

From glucose and insulin oscillations to oxidation, inflammation, and insulin resistance, a modern diet full of sugar and refined carbohydrates can be a potential driver of psychological distress. For more details about how a whole-food, low-carbohydrate diet can help with specific psychiatric disorders, please visit our guide, The food-mood connection.

If you are struggling with mental health issues and taking medication, we have a lot more information on this topic in our guide, Low carb and mental health: Getting started and managing medications. We also have an FAQ that addresses many common questions and concerns about the links between diet and mental health.

/ Dr. Georgia Ede, MD

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Videos about low carb

  1. These are just three examples of human clinical studies illustrating how blood sugar and insulin respond to high-carbohydrate foods. Many other examples exist.

    The American Journal of Clinical Nutrition 1998: Acute effects on insulin sensitivity and diurnal metabolic profiles of a high-sucrose compared with a high-starch diet [randomized trial; moderate evidence]

    Journal of Nutrition 2003: Physiological validation of the concept of glycemic load in lean young adults [non-controlled study; weak evidence]

    American Journal of Clinical Nutrition 2008: Twenty-four-hour endocrine and metabolic profiles following consumption of high-fructose corn syrup-, sucrose-, fructose-, and glucose-sweetened beverages with meals [randomized trial; moderate evidence]

  2. A strong relationship between blood glucose and and brain glucose was shown in a large observational study of more than 19,000 children:

    New England Journal of Medicine 2012: Relationship between cerebrospinal fluid glucose and serum glucose [cross-sectional study; weak evidence]

  3. Neuroscience & Biobehavioral Reviews 2002: Carbohydrate ingestion, blood glucose and mood [overview article; ungraded]

    Journal of Pediatrics 1995: Enhanced adrenomedullary response and increased susceptibility to neuroglycopenia: mechanisms underlying the adverse effects of sugar ingestion in healthy children [non-controlled study; weak evidence]

  4. Although it is difficult to “prove” that the symptoms come from the rise and fall in blood sugar, clinical experience suggests that is the case. [clinical experience; very weak evidence]

  5. Frontiers in Neuroscience 2014: Neural pathways that control the glucose counterregulatory response [overview article; ungraded]

  6. [clinical experience; weak evidence]

  7. In one study, boys who drank a sweetened beverage experienced a four-fold increase in adrenaline 4-5 hours later, and they reported symptoms such as anxiety, shakiness, and difficulty concentrating:

    Journal of Pediatrics 1995: Enhanced adrenomedullary response and increased susceptibility to neuroglycopenia: mechanisms underlying the adverse effects of sugar ingestion in healthy children [randomized controlled trial; moderate evidence]

  8. Molecular Psychology 2016: A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression. [observational study, weak evidence]

    Frontiers in Psychiatry 2019: What is the role of dietary inflammation in severe mental illness? A review of observational and experimental findings. [overview article; ungraded]

  9. Oxidative Medicine and Cellular Longevity 2017: Oxidative stress: harms and benefits for human health[overview article; ungraded]

  10. Cellular Physiology and Biochemistry 2017: Antioxidants maintain cellular redox homeostasis by elimination of reactive oxygen species [overview article; ungraded]

  11. Medicinal Research Reviews 2015: Postprandial dysmetabolism and oxidative stress in type 2 diabetes: pathogenetic mechanisms and therapeutic strategies [overview article; ungraded]

  12. Journal of Neuroinflammation 2013: Neuroinflammation and psychiatric illness [Review article of clinical trials and observational studies;
    weak to moderate evidence]

  13. Antioxidants & Redox Signaling 2013: Dietary (poly)phenolics in human health: structures, bioavailability, and evidence of protective effects against chronic diseases [overview article; ungraded]

  14. Current Topics in Behavioral Neurosciences 2017: Evidence for inflammation-associated depression [overview article; ungraded]

    Psychiatric Clinics of North America 2016: Bipolar disorder and inflammation [overview article; ungraded]

    International Journal of Molecular Sciences 2017: Neuroinflammation and oxidative stress in psychosis and psychosis risk [overview article; ungraded]

  15. The following analysis of observational studies suggests an association between inflammation and mood disorders. As with all observational studies, it does not prove causation but suggests areas for further research.

    Translational Psychiatry 2019: Inflammation-related biomarkers in major psychiatric disorders: a cross-disorder assessment of reproducibility and specificity in 43 meta-analyses [meta-analyses of case-control studies; weak evidence]

  16. Depression and Anxiety 2013: Cytokine targets in the brain: impact on neurotransmitters and neurocircuits
    [overview article; ungraded]

  17. Journal of the Academy of Nutrition & Dietetics 2012: Effect of dietary linoleic acid on markers of inflammation in healthy persons: a systematic review of randomized controlled trials [strong evidence] 

  18. Prostaglandins, Leukotrienes, and Essential Fatty Acids 2018: Omega-6 fatty acids and inflammation [overview article; ungraded]

  19.  Experimental Biology and Medicine 2008: The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases [overview article; ungraded]

  20. Psychoneuroendocrinology 2018: Omega-3 and omega-6 fatty acid levels in depressive and anxiety disorders [observational study; weak evidence]

    Journal of Clinical Psychiatry 2016: Omega-3 and omega-6 polyunsaturated fatty acids in bipolar disorder: a review of biomarker and treatment studies [observational study; weak evidence]

    Journal of the Canadian Academy of Child and Adolescent Psychiatry 2016: Omega-6 to omega-3 fatty acid ratio in patients with ADHD: a meta-analysis [meta-analysis of case-control studies; weak evidence]

    Psychiatry Research 2013: Red blood cell polyunsaturated fatty acids measured in red blood cells and schizophrenia: a meta-analysis[meta-analysis of case-control studies; weak evidence]

    Nutrients 2017: Relationship between long chain n-3 polyunsaturated fatty acids and autism spectrum disorder: systematic review and meta-analysis of case-control and randomized controlled trials [meta-analysis of case-control studies; weak evidence]

  21. Current Topics in Behavioral Neurosciences 2017: Evidence for inflammation-associated depression [overview article; ungraded]

    Lancet Psychiatry 2015: Inflammation and immunity in schizophrenia: implications for pathophysiology and treatment [overview article; ungraded]

  22. Neuropharmacology 2018: Insulin resistance, an unmasked culprit in depressive disorders: promises for interventions [overview article; ungraded]

    JAMA Psychiatry 2017: Impaired glucose homeostasis in first-episode schizophrenia: a systematic review and meta-analysis [systematic review of case-control studies; weak evidence]

    Journal of Diabetes Science and Technology 2008: Alzheimer’s disease is type 3 diabetes: evidence reviewed [overview article; ungraded]

  23. PLoS One 2014: Insulin resistance induced by hyperinsulinemia coincides with a persistent alteration at the insulin receptor tyrosine kinase domain [test tube study; very weak evidence]

  24. Nature Reviews. Neurology 2018: Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums [overview article; ungraded]

  25. Acta Diabetologia 2014: Evidence for altered transport of insulin across the blood-brain barrier in insulin-resistant humans [observational study; weak evidence]

  26. Journal of Neuroscience Research 2017: Cerebral hypoperfusion and glucose hypometabolism: key pathophysiological modulators promote neurodegeneration, cognitive impairment, and Alzheimer’s disease [overview article; ungraded]

  27. Although quality outcome trials are lacking, the mechanistic data is very encouraging.

    Neuroscience and Biobehavioral Reviews 2018: Ketogenic diet as a metabolic therapy for mood disorders: evidence and developments [review article; ungraded]

    Frontiers in Psychiatry 2017: The current status of the ketogenic diet in psychiatry [review article; ungraded]

  28. American Journal of Clinical Nutrition 2009: Food insulin index: physiologic basis for predicting insulin demand evoked by composite meals [non-controlled study; weak evidence]

  29. Epilepsia 2018: Effect of modified Atkins diet in adults with drug-resistant focal epilepsy: a randomized controlled trial [moderate evidence]

    Acta Neurologica Scandinavica 2017: A randomized controlled trial of the ketogenic diet in refracatory childhood epilepsy [moderate evidence]

    Epilepsy Research 2016: Evaluation of a simplified modified Atkins diet for use by parents with low levels of literacy in children with refractory epilepsy: a randomized controlled trial [moderate evidence]

  30. U.S. Institute of Medicine of the National Academies 2005: Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids 2005 [review article; ungraded]

  31. Frontiers in Endocrinology 2018: Unraveling the regulation of hepatic gluconeogenesis [overview article; ungraded]

  32. Neurochemistry International 2017: Brain energy metabolism spurns fatty acids as fuel due to their inherent mitotoxicity and potential capacity to unleash neurodegeneration [review of mechanisms; ungraded]

  33. Journal of Lipid Research 2014: Ketogenic diets, mitochondria, and neurological diseases [review of mechanisms; ungraded]

  34. Journal of Neurochemistry 2015: Effects of ketone bodies in Alzheimer’s disease in relation to neural hypometabolism, ß-amyloid toxicity, and astrocyte function [review of mechanisms; ungraded]

    Journal of Clinical Investigations 1967: Brain metabolism during fasting [non-controlled trial; weak evidence]

    Critical Care 2011: Clinical review: Ketones and brain injury. [overview article; ungraded]

    Journal of Cerebral Blood flow and Metabolism 2017: Inverse relationship between brain glucose and ketone metabolism in adults during short-term moderate dietary ketosis: A dual tracer quantitative positron emission tomography study [non-controlled trial; weak evidence]

  35. Frontiers in Molecular Neuroscience 2016: Can ketones help rescue brain fuel supply in later life? Implications for cognitive health during aging and the treatment of Alzheimer’s disease [overview article; ungraded]

  36. Journal of Alzheimer’s Disease 2015: Lower brain 18F-fluorodeoxyglucose uptake but normal 11C-acetoacetate metabolism in mild Alzheimer’s disease dementia [case-control study; very weak evidence]

    Experimental Gerontology 2018: A cross-sectional comparison of brain glucose and ketone metabolism in cognitively healthy older adults, mild cognitive impairment and early Alzheimer’s disease [case-control study; very weak evidence]

    Annals of the New York Academy of Sciences 2016: Can ketones compensate for deteriorating brain glucose uptake during aging? Implications for the risk and treatment of Alzheimer’s disease [overview article; ungraded]

  37. Our policy at Diet Doctor is that higher ketone levels are not necessarily “better” than lower levels for general health and weight loss. However, this may not be the case in neurologic conditions. Although we need more high quality research, the initial hypothesis is that higher ketone levels, to a degree, may be more beneficial than lower levels in the brain.