Metabolism gets a lot of press.
You’ve probably heard that it’s important to have a good metabolism to stay in shape.
Recent research is now shedding light on metabolism’s role in mental health.
Your body’s ability to properly utilize micronutrients, glucose specifically, has a profound effect on your mental state.
There are many reasons for this, most of which are the interplay between blood glucose, hormones, and catecholamines.1Eberhard Barth, Gerd Albuszies, Katja Baumgart, Martin Matejovic, Ulrich Wachter, Josef Vogt, Peter Radermacher, Enrico Calzia. Glucose metabolism and catecholamines, Crit Care Med. 2007
In fact, blood sugar may be the most influential determinant of your body’s physiological stress hormone response.
Once in circulation, these stress hormones can dictate your mental state.
In this article, I’ll explain the connection between blood sugar and stress hormones, how blood sugar directly affects your mood, and what you can do to optimize this system.
How Does Diet Affect Mental Health?
We know that mental health is highly influenced by diet.2A A Kulkarni, B A Swinburn, J Utter. Associations between diet quality and mental health in socially disadvantaged New Zealand adolescents, Eur J Clin Nutr. 2015
As many countries worldwide adopt, a western-style diet made up of mostly fast foods, fried foods, sweets, refined grains, processed meat, and a reduction of fruit/vegetable mental health conditions continue to worsen.3Anu Ruusunen, Soili M Lehto, Jaakko Mursu, Tommi Tolmunen, Tomi-Pekka Tuomainen, Jussi Kauhanen, Sari Voutilainen. Dietary patterns are associated with the prevalence of elevated depressive symptoms and the risk of getting a hospital discharge diagnosis of depression in middle-aged or older Finnish men, J Affect Disord. 2014
In fact, the Western-style diet has been independently associated with a greater risk of developing anxiety and depression.4A A Kulkarni, B A Swinburn, J Utter. Associations between diet quality and mental health in socially disadvantaged New Zealand adolescents, Eur J Clin Nutr. 2015
One of the major reasons for this may be the western diet’s influence on blood sugar dysregulation.
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Blood Sugar and Mental Health
Much has been written about the connection between blood sugar and mental health.
We know that people with diabetes and chronically elevated blood sugar are 2-3 times higher and have depression.5Tapash Roy, Cathy E Lloyd. Epidemiology of depression and diabetes: a systematic review, J Affect Disord. 2012
Anxiety is also present in 40% of diabetics (type 1 and type 2).6Allison B Grigsby, Ryan J Anderson, Kenneth E Freedland, Ray E Clouse, Patrick J Lustman. Prevalence of anxiety in adults with diabetes: a systematic review, J Psychosom Res. 2002
This is also a bidirectional relationship as depression raises diabetes risk by over 60%.7Briana Mezuk, William W Eaton, Sandra Albrecht, Sherita Hill Golden. Depression and type 2 diabetes over the lifespan: a meta-analysis, Diabetes Care. 2008
There are a number of physiological reasons why blood sugar dysregulation negatively influences mental health.
Both hyper and hypoglycemia have been tied to increased heart rate, blood pressure, and overall inflammation.
These physical markers are also associated with higher instances of anxiety and depression.8Afework Edmealem and Caridad Sanchez Olis. Factors Associated with Anxiety and Depression among Diabetes, Hypertension, and Heart Failure Patients at Dessie Referral Hospital, Northeast Ethiopia, Behav Neurol. 2020
While we know that mental health issues are multifactorial, there is plenty of evidence to assume that controlling your blood sugar can help improve overall cognitive function.
Blood Sugar, Depression, and Anxiety
Depression and anxiety can be tied directly to both hyper and hypoglycemic conditions.
A study examining depression in 3,742 diabetic patients showed that individuals who have experienced severe hyperglycemic events had more than twice the risk of depression than those who had not experienced a hyperglycemic event.
And those patients who experienced severe hypoglycemic events had a 75% elevated risk of depression.
The bidirectional relationship likely enables a harmful feed-forward cycle, with depression and severe glycemic events increasing the other’s risk.9Paola Gilsanz, Andrew J Karter, Michal Schnaider Beeri, Charles P Quesenberry Jr, Rachel A Whitmer. The Bidirectional Association Between Depression and Severe Hypoglycemic and Hyperglycemic Events in Type 1 Diabetes, Diabetes Care. 2018
Another meta-analysis of 24 studies showed that depression is associated with hyperglycemic conditions.10P J Lustman, R J Anderson, K E Freedland, M de Groot, R M Carney, R E Clouse. Depression and poor glycemic control: a meta-analytic review of the literature, Diabetes Care. 2000
For many people, anxiety is a more pressing condition when blood sugar is dysregulated.
Hyperglycemia specifically has been shown to incite anxiety.11L A Gonder-Frederick, D J Cox, S A Bobbitt, J W Pennebaker. Mood changes associated with blood glucose fluctuations in insulin-dependent diabetes mellitus, Health Psychol. 1989
The science seems to be clear that your quality of life becomes substantially diminished when you have dysregulated blood sugar.12Andrew J Green, Kathleen M Fox, Susan Grandy, SHIELD Study Group. Self-reported hypoglycemia and impact on quality of life and depression among adults with type 2 diabetes mellitus, Diabetes Res Clin Pract. 2012
The most important thing to understand is that this is all in your control.
A diet high in low glycemic foods, aka junk food, can help eliminate depression, anxiety, and psychiatric disorders.13Fahimeh Haghighatdoost, Leila Azadbakht, et al. Glycemic index, glycemic load, and common psychological disorders, Am J Clin Nutr. 2016
Blood Sugar and Cognitive Decline
Dysregulated blood sugar can be a catalyst for overall cognitive decline.14Laís S. S. Ferreira, Caroline S. Fernandes, Marcelo N. N. Vieira, and Fernanda G. De Felice. Insulin Resistance in Alzheimer’s Disease, Front Neurosci. 2018
One of the big reasons is the interplay of insulin and insulin resistance.
It’s been shown that insulin resistance can slow down cognitive function.
This may be due to insulin being a vasodilator.
It increases blood flow to promote glucose delivery to the muscle, tissue, and the brain.
In insulin-resistant individuals, the vasodilator function is blunted, which leads to impairment of insulin action coupled to a decrease in the delivery of blood and glucose to the brain.15E J Barrett, E M Eggleston, A C Inyard, H Wang, G Li, W Chai, Z Liu. The vascular actions of insulin control its delivery to muscle and regulate the rate-limiting step in skeletal muscle insulin action, Diabetologia. 2009
This is one way to explain cognitive disorders associated with insulin resistance and blood sugar dysregulation, including:
- Fatigue16Sanjay Kalracorresponding and Rakesh Sahay. Diabetes Fatigue Syndrome
, Diabetes Ther. 2018
- Brain Fog17A Moheet, S Mangia, and ER Seaquist. Impact of diabetes on cognitive function and brain structure
, Ann N Y Acad Sci. 2016
- Memory Loss18Jenna Bloemer, Subhrajit Bhattacharya, Rajesh Amin, Vishnu Suppiramaniam. Impaired insulin signaling and mechanisms of memory loss, Prog Mol Biol Transl Sci. 2014
- Alzheimer’s Disease and Dementia19Geert Jan Biessels and Florin Despa. Cognitive decline and dementia in diabetes: mechanisms and clinical implications, Nat Rev Endocrinol. 2019
- ADHD20Richard J. Johnson, MD, et al. Attention-Deficit/Hyperactivity Disorder: Is it Time to Reappraise the Role of Sugar Consumption?, Postgrad Med. 2013
Blood Sugar and Metabolism
Buckle up because we’re getting into some basic biology.
Your blood sugar is measured by the amount of glucose circulating in your bloodstream.
Glucose is the end product of either carbohydrate being broken down from food, or stored glycogen being mobilized endogenously.
It’s important to note that glucose is the fastest acting fuel source for your cells’ ability to produce ATP.
ATP is the main form of cellular energy that comes from a series of biochemical reactions that break down glucose in the cellular mitochondria and fuel virtually every energy-requiring process in the body.21Alberts B, Johnson A, Lewis J, et al.. Molecular Biology of the Cell. 4th edition., Garland Science; 2002
Despite what your keto zealot friends tell you, glucose is necessary to power your body and brain.
But there’s a lot more to the story.
Mainly, how does your body know how much glucose to keep in the blood at any given moment?
Blood Sugar Homeostasis
Your body is always trying to keep things balanced.
We refer to this as homeostasis.22Freddy D Jeanneteau, W Marcus Lambert, Naima Ismaili, Kevin G Bath, Francis S Lee, Michael J Garabedian, Moses V Chao. BDNF and glucocorticoids regulate corticotrophin-releasing hormone (CRH) homeostasis in the hypothalamus, Proc Natl Acad Sci U S A. 2012
Regarding blood sugar, your body wants to keep the optimal amount of glucose in the blood in a goldilocks zone. Not too much, not too little.23Alex Rafacho, Henrik Ortsäter, Angel Nadal, Ivan Quesada. Glucocorticoid treatment and endocrine pancreas function: implications for glucose homeostasis, insulin resistance and diabetes, J Endocrinol. 2014
There are hormones, insulin, and glucagon, excreted from the pancreas and control the flow of glucose in and out of your bloodstream.
However, these are not the only hormones affecting glucose in your blood.
Stress hormones like cortisol are also directing glucose in the blood.
Oddly enough, blood glucose is also dictating cortisol.
This interplay of glucose and hormones can have profound effects on your mood.
Understanding and ultimately working to optimize your hormones through blood sugar control can greatly improve your mental health, sharpen your focus, and boost overall cognitive abilities.
The “Fight Or Flight” Sympathetic Nervous System
Stress and blood sugar have a special relationship that’s over 2 million years old.
Our body’s stress response has evolved to maintain blood sugar homeostasis.
It does this through the autonomic nervous system, which pulls the string of the HPA Axis.
For most of these 2 million years, keeping blood sugar stable was easy.But now our modern diet provides more glucose than our bodies are designed to handle, and this excess is playing out in rising cases of metabolic disorders.
Higher metabolic disorders and blood glucose dysregulation means rising stress in the body.
When a stressor presents itself, your brain switches into the sympathetic nervous system, also known as fight or flight.24A L Curtis, S M Lechner, L A Pavcovich, R J Valentino. Activation of the locus coeruleus noradrenergic system by intracoerulear microinfusion of corticotropin-releasing factor: effects on discharge rate, cortical norepinephrine levels and cortical electroencephalographic activity, J Pharmacol Exp Ther. 1997
This is in direct opposition to your autonomic nervous system’s chill, parasympathetic mode commonly referred to as “rest and digest.”
When your body is in fight or flight, it priorities survival over everything else.
Your body’s ability to make sex hormones, rest, and digest is totally diminished.
Meanwhile, your heart rate increases, your eyesight sharpens, your attention is piqued, and you become more alert.25Sivan Rotenberg and Jennifer J. McGrath. Inter-relation between autonomic and HPA axis activity in children and adolescents, Biol Psychol. 2017
These physical reactions naturally require increased energy expenditure.
Your body delivers this in the form of glucose to be used by the cell.
Cortisol is what steps on the gas and gets the energy to the cells for optimal response.26R M Sapolsky, L M Romero, A U Munck. How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions, Endocr Rev. 2000
Stress and Blood Sugar
When we discuss “stress,” it’s important to understand the different forms of stress we’re talking about.
Of course, there are emotional stresses like deadlines, sitting in traffic, or trying to book a flight.
However, most chronic stressors are physiological.
You can experience a physical stressor from chemicals in your environment, chemicals in your food, and inflammation.
The physiological stress response is controlled through your body’s HPA axis.28Sean M Smith, Wylie W Vale. The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress, Dialogues Clin Neurosci. 2006
Your HPA Axis is the information superhighway made up of your hypothalamus, pituitary, and adrenal glands.
The HPA Axis works within your sympathetic, aka fight or flight, nervous system.
Its job is to ultimately keep the body in a balanced state of homeostasis by supercharging energy delivery, aka glucose, to the muscles, organs, and tissues that need it.29Sharon DeMorrow. Role of the Hypothalamic–Pituitary–Adrenal Axis in Health and Disease, Int J Mol Sci. 2018
When your brain senses a stressor, both emotional and physical, your hypothalamus communicates to your pituitary gland to alert the adrenal glands that the body needs more glucocorticoids (aka cortisol) circulation.30Lahari Vuppaladhadiam, et al. Corticotropin-Releasing Factor Family: A Stress Hormone-Receptor System’s Emerging Role in Mediating Sex-Specific Signaling, Cells. 2020
In many instances, your HPA Axis kicks in simply because a high glycemic insulin response was triggered and left the blood in a hypoglycemic state.31R A Donald, E A Espiner. The plasma cortisol and corticotropin response to hypoglycemia following adrenal steroid and ACTH administration, J Clin Endocrinol Metab. 1975
The HPA Axis makes glucocorticoids like cortisol to help restore blood glucose available, which is good.
Unfortunately, you now have increased circulating stress hormones, which can wreak havoc in other parts of your body, including your brain.
The HPA Axis’ Diurnal Pattern and Circadian Rhythm
Under basal conditions of little or no stress, cortisol secretion follows a diurnal pattern characterized by high concentrations early in the morning and a steady decline throughout the day.32Michael R. Jarcho, et al. Dysregulated diurnal cortisol pattern is associated with glucocorticoid resistance in women with major depressive disorder, Biol Psychol. 2014
This is known as the “diurnal slope.”
This diurnal pattern is designed to wake up in the morning, have enough energy to get through the day, and then fall asleep and stay asleep at night. This is also referred to as your circadian rhythm.
As cortisol lowers throughout the day, your body produces other hormones, including testosterone, estrogen, and melatonin.
An overactive HPA Axis can lead to a disrupted circadian rhythm. Cortisol output is weak in the morning and potent in the evening.33R Leproult, G Copinschi, O Buxton, E Van Cauter. Sleep loss results in an elevation of cortisol levels the next evening, Sleep. 1997
A disrupted circadian rhythm and diurnal cortisol pattern can result in daytime fatigue, sleep problems, illness, and mood disorders like depression and anxiety.34Thaddeus W W Pace, Fang Hu, Andrew H Miller. Cytokine-effects on glucocorticoid receptor function: relevance to glucocorticoid resistance and the pathophysiology and treatment of major depression, Brain Behav Immun. 2007
Dysregulated blood sugar is a recipe for an overactive HPA Axis response, which leads to a disrupted circadian rhythm and all the adrenal-related problems that follow.35R A Donald, E A Espiner. The plasma cortisol and corticotropin response to hypoglycemia following adrenal steroid and ACTH administration, J Clin Endocrinol Metab. 1975
How Does Elevated Blood Sugar Effect Cortisol?
When cortisol is released, then blood glucose rises.36N Bergmann, F Gyntelberg, J Faber. The appraisal of chronic stress and the development of the metabolic syndrome: a systematic review of prospective cohort studies, Endocr Connect. 2014
This is due to cortisol’s promotion of gluconeogenesis and its primary function of making glucose available in the blood.37Taiyi Kuo, Allison McQueen, Tzu-Chieh Chen, Jen-Chywan Wang. Regulation of Glucose Homeostasis by Glucocorticoids, Adv Exp Med Biol. 2015
On the other hand, chronically high blood glucose keeps cortisol pumping, and chronically high cortisol keeps blood sugar elevated.38Guido Di Dalmazi, et al. Glucocorticoids and Type 2 Diabetes: From Physiology to Pathology, Journal of Nutrition and Metabolism. 2012
And because the HPA Axis is a negative feedback loop, eventually, this whole system will stop, and you will begin to experience dysregulated cortisol.39J. M. H. M. REUL, E. R. DE KLOET. Two Receptor Systems for Corticosterone in Rat Brain: Microdistribution and Differential Occupation, Endocrinology. 1985
By stabilizing your blood sugar with diet, supplementation, and adequate sleep, you can effectively modulate your HPA Axis and stress hormone response.
Negative Feedback Loop
The negative feedback loop of the HPA Axis means that when the hypothalamus senses cortisol in circulation, it discontinues the production of cortisol in times of need.40Julia K Gjerstad, Stafford L Lightman, and Francesca Spiga. Role of glucocorticoid negative feedback in the regulation of HPA axis pulsatility, Stress. 2018
This throws off the entire diurnal pattern of daily hormone production.
This happens when your cortisol is abnormally raised due to exposure frequent exposure to stressors such as high-glycemic foods, environmental toxicity, and inflammation.
This means low cortisol in the morning and too much at night.
We refer to this as “wired and tired.”41R McKenzie, A O’Fallon, J Dale, M Demitrack, G Sharma, M Deloria, D Garcia-Borreguero, W Blackwelder, S E Straus. Low-dose hydrocortisone for treatment of chronic fatigue syndrome: a randomized controlled trial, JAMA. 1998
Your morning cortisol is necessary to get you out of bed and feel vibrant, while low nighttime cortisol translates into higher melatonin and deeper sleep.42Zahra Zamanian, Mansooreh Dehghani, and Hassan Hashemi. Outline of Changes in Cortisol and Melatonin Circadian Rhythms in the Security Guards of Shiraz University of Medical Sciences, Int J Prev Med. 2013
As dysregulated cortisol becomes chronic, you’ll begin to experience more serious issues leading eventually to Cushing’s syndrome.43Andrea M Isidori, et al. The hypertension of Cushing’s syndrome: controversies in the pathophysiology and focus on cardiovascular complications, J Hypertens. 2015
In fact, depression, among other psychiatric disturbances, are prevalent in Cushing’s syndrome.44Alice Tang, Anthony J O’Sullivan, Terry Diamond, Andrew Gerard, and Peter Campbell. Psychiatric symptoms as a clinical presentation of Cushing’s syndrome, Ann Gen Psychiatry. 2013
How To Fix Metabolism and Brain Health
If you are like most people eating the western diet, you will benefit from making a few changes to optimize your mental health.
Some dietary changes to make include:
- Lowering sugar and carbohydrate intake
- Eliminating high fructose corn syrup
- Eliminating or substantially lowering processed foods
- Eliminating fried foods
- Eating whole foods like fruit, vegetables, and high-quality animal products.
- Eat more protein
- Avoid carbohydrates in the morning.
- Try intermittent fasting
Nootropics and Supplements That Can Help
This is a shortlist of nootropics and supplements that can help regulate your HPA Axis stress response and blood sugar status.
Devices That Can Help Stabilize Stress and Blood Sugar
If you deal with mental health disorders or cognitive decline, stabilizing your blood sugar should be one of the first things you do to boost your brain naturally.
As this article highlights, there are many connections between blood sugar, metabolism, stress, and mental health.
In fact, it’s widely accepted that stress lies at the heart of most chronic diseases. This includes mental health issues.
Fortunately, there are many low-cost, low-risk methods to boost your metabolism for cognitive enhancement.
Making simple changes to your diet and adding in beneficial supplements and nootropics is one of the most effective ways to boost your metabolism.
Tracking your numbers with a device like a CGM or Lumen can help you further optimize your dietary and lifestyle choices.
By following a drug-free, holistic protocol to lower stress, you will build a solid foundation for boosting cognition and overall life quality.