The link between sugar and depression

 

Our food choices have a huge effect on our mood and emotions. One good example of this food-mood connection is the link between sugar consumption and mood disorders, including depression. Studies show that eating too many refined carbohydrates may increase our risk for depression and several other chronic diseases. Below I will go a little deeper on this evidence-based link between sugar and depression.

Depression is today on the rise, and studies show that diet could be one of the factors to blame for this depression epidemic we are witnessing. According to a study considering 3486 participants, published in The British Journal of Psychiatry, people who ate the highest amount of processed foods (sweetened desserts, fried food, processed meat, refined grains, and high-fat dairy products) had a 58% increased risk of depression while the people who ate the highest amount of whole foods (fruits and vegetables) had a 26% decreased risk of depression after 5 years, meaning a whole food diet protects against depression [1]. Randomized controlled trials (the most reliable type of clinical studies) showed that a healthy diet rich in whole foods can indeed prevent and improve depressive symptoms [2-4]. In fact in one study, the positive results were found in as little as 3 weeks [4].

It is now recognized that depression can be due to nutritional imbalances, such as a lack of certain vitamins, minerals, amino acids, essential fatty acids, disturbances in the gut microbiota, and unstable blood sugar levels as the brain needs a stable supply of glucose.

A correlation between sugar consumption and the prevalence of depression has long been observed [5, 6]. For example, a study, including 1878 high-school students, found that people who drank regularly sugary drinks had higher depressive symptoms than the ones who didn’t drink any soda [7]. Indeed, a meta-analysis study considering 15 other studies and including 20,572 cases of depression among almost 350,000 participants, found that sugary drink consumption increased the risk of depression by 36% [8]. Another study published in Scientific Reports, that analyzed the data of 23,245 people, showed that not only beverages but also sweet food increased the risk of depression and mental disorders [9].

Fast foods and baked goods like muffins, croissants, pastries, doughnuts, cakes and other commercially made baked goods also increase the risk of depression. In one study, researchers found a 38% higher risk of depression in those eating the highest amount of baked goods compared with those eating the least [10]. Here, not only sugar may play a role, but also the trans-fats contained in these products, as suggested by the authors [10].

Moreover, refined carbohydrates (sugar and flour products) not only increase the risk of mood disorders, but they are also associated with higher levels of fatigue and less alertness within the first hour after consumption (what is known as “sugar crash”) [11].

 

Not all carbs are bad – mind the difference between refined and complex carbs

However, please do mind that not all carbohydrates are bad. The quality of carbohydrates does matter – a lot! A study analyzed the quantity and quality of carbs consumed by almost 70,000 women. They studied the glycemic index (GI) of each food consumed. Foods with high GI raise blood sugar more +-and are often made from refined carbs (simple sugars and refined grains), while whole foods, such as vegetables and fruits, have lower GIs. They found that women who ate high-GI foods had a higher risk of depression than women who ate lower GI foods. In addition, women who ate a higher amount of low-GI foods, such as vegetables and fruits, had a low risk of depression [6]. Thus, these results show that it’s not the carbs in general that matter, but the type of carbs, and suggest that high-GI diets could be a risk factor for depression. In fact, consuming whole grains, legumes, vegetables and fruits (high in complex carbs), which are included in the healthiest diets like the Mediterranean and the MIND diet, have been linked to a reduced risk of mental disorders, as shown by many (really many!) studies (for example  [12-15]).

 

Diabetes and depression: same biological origins?

A relationship between diabetes and depression has been quite well documented, as shown in these review articles that analyzed several other articles on the topic [16, 17]: people with diabetes have an increased prevalence of depression and vice-versa. Depressive symptoms are a risk factor for the development of type 2 diabetes, but they have also been shown to contribute to hyperglycemia and diabetic complications.  Evidence is growing that depression and type 2 diabetes share biological origins, including the overactivation of the immune system leading to an exacerbated inflammatory response, and dysregulation of the hypothalamic-pituitary-adrenal axis (which is linked to mental disorders).

 

Why is sugar related to depression?

There are several ways through which sugar may be related to depression [18], namely:

 

Inflammation

Several studies have found that sugar consumption increases inflammation [19], and inflammation is linked to depression [20, 21]. In fact, scientists have acknowledged a bidirectional relationship between depression and inflammation [22]. Added sugars may also trigger specific inflammatory processes in the brain (neuroinflammation), which are in turn linked with impaired cognitive function [18].

 

Vitamin depletion

Besides not providing any vitamins, sugar actually depletes our body from important vitamins such as the B vitamins (which are essential for mood), because it uses them for its catabolism [23]. B-vitamins are essential for neuronal function and deficiencies (for example of B1, B3, folate, vitamin B6 and vitamin B12) have been linked to depression [24, 25], and supplementation with these vitamins has been found helpful to prevent and improve depressive symptoms [26].

 

BDNF suppression

Brain-derived neurotrophic factor (BDNF) is a protein critical for brain health. It stimulates the formation of new neurons, helps protect the brain and regulates energy homeostasis in the brain, among other functions. Low levels of BDNF have been associated with mental health conditions [27].

A refined sugar and high-fat diet has been shown to reduce BDNF levels [28]. BDNF modulates glucose metabolism, stimulates glucose transport and mitochondrial biogenesis and protects neurons against injury [29], so taking something that lowers our BDNF levels is not a good idea.

 

Gut microbiota dysfunction

It is now known that our gut health influences our brain health in several aspects.

A high sugar diet alters our gut health by allowing the growth of harmful bacteria in our gut. There is also growing evidence that sugar can increase intestinal permeability, by inhibiting microbes that maintain the intestinal barrier and by interfering with the proteins necessary to maintain a healthy intestinal barrier [30].

This results in an increased passage of bacteria through the intestinal barrier to the rest of our body, and the subsequent activation of proinflammatory pathways [31]. Indeed, higher consumption of fructose has been linked to an increased presence of bacterial-produced toxins in the blood of humans, which is an indication of increased intestinal permeability [32].

Microbiota-induced inflammation may be a risk factor for the development of depression [18]. In fact, bacteria associated with intestinal inflammation have been found to be overrepresented in depressed individuals [33]. Also, there is some evidence that probiotics (healthy bacteria we can eat) may decrease depression symptoms [34].

 

Dopamin dysregulation

Dopamine is the main brain chemical (neurotransmitter) involved in our pleasure, reward and motivation responses.

Sugar consumption tends to stimulate dopamine: even a sip of sugary beverage immediately activates rewards areas within our brain [35]. And the more sugar is eaten, the more dopamine is released in our brain. In other words, the more sugar you eat, the better you feel, so you keep wanting to consume more. However, when we overstimulate this reward system, problems such as loss of control and cravings (so, addiction symptoms) start showing up. Also, in chronic sugar consumption, there is a decreased dopamine sensitivity, meaning that although we have more dopamine, our brain doesn’t feel it, and we need to consume more and more sugar to feel good [36]. Therefore, over long term, excessive sugar intake is associated with dopamine dysregulation, and dopamine dysregulation is associated with depression [37]. This means that chronic sugar consumption can interfere with the brain’s reward system, inducing lack of pleasure and motivation, which are both hallmarks of depression.

 

Excessive free radical production

Excessive free radicals in our body (oxidative stress) induces toxic effects, such as cellular destruction, inflammation, and accelerated aging.

Studies have shown that depression is characterized by elevated levels of oxidative stress [38]. On the other hand, accumulating scientific research suggests that added sugar consumption can induce oxidative stress. After a high dose of sugar, even healthy individuals have an immediate increase in free radical levels [39].

 

Insulin resistance

Insulin is a key hormone that allows glucose to enter into the cells for energy. Insulin resistance develops when the receptors become less sensitive to insulin. This results in higher levels of blood glucose, whereas the cells are deprived of their main fuel.

Insulin receptors are present throughout the brain, and they play a central role in regulating the use of glucose for brain energy. Some scientists have even suggested that depression could be caused by the brain’s insulin resistance and the resulting disruption of energy utilization by neurons [40, 41]. And indeed, it is known that adults with insulin resistance have an increased risk of depression [42].

Excessive sugar consumption is a strong cause of insulin resistance. Even a short-term, high-fructose diet can increase fasting glucose levels in healthy men and women. In fact, even one week of fructose overfeeding is sufficient to decrease insulin sensitivity [43].

 

Advanced Glycation End-Products

Advanced glycation end-products (AGEs) are toxic molecules that form when sugar molecules react with proteins, fats, or other compounds in the body.

Excessive added sugar consumption promotes AGE formation by increasing the availability of glucose and fructose, which are then irreversibly converted to AGEs within the body [44].

Once formed, AGEs are associated with many adverse effects, including oxidative stress, inflammation, and neurocognitive dysfunction [45, 46].

A study in 862 adults found that those with elevated AGE accumulations in skin tissue had a 42% increase in the risk of depression [47]. Moreover, there was a positive association between measured AGE levels and the severity of depressive symptoms.

 

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References

  1. Akbaraly, T.N., et al., Dietary pattern and depressive symptoms in middle age. Br J Psychiatry, 2009. 195(5): p. 408-13.
  2. Agarwal, U., et al., A multicenter randomized controlled trial of a nutrition intervention program in a multiethnic adult population in the corporate setting reduces depression and anxiety and improves quality of life: the GEICO study. Am J Health Promot, 2015. 29(4): p. 245-54.
  3. Parletta, N., et al., A Mediterranean-style dietary intervention supplemented with fish oil improves diet quality and mental health in people with depression: A randomized controlled trial (HELFIMED). Nutr Neurosci, 2019. 22(7): p. 474-487.
  4. Francis, H.M., et al., A brief diet intervention can reduce symptoms of depression in young adults – A randomised controlled trial. PLoS One, 2019. 14(10): p. e0222768.
  5. Westover, A.N. and L.B. Marangell, A cross-national relationship between sugar consumption and major depression? Depress Anxiety, 2002. 16(3): p. 118-20.
  6. Gangwisch, J.E., et al., High glycemic index diet as a risk factor for depression: analyses from the Women’s Health Initiative. Am J Clin Nutr, 2015. 102(2): p. 454-63.
  7. Pabayo, R., et al., Sweetened beverage consumption is a risk factor for depressive symptoms among adolescents living in Boston, Massachusetts, USA. Public Health Nutr, 2016. 19(17): p. 3062-3069.
  8. Kang, D., Y. Kim, and Y. Je, Non-alcoholic beverage consumption and risk of depression: epidemiological evidence from observational studies. Eur J Clin Nutr, 2018. 72(11): p. 1506-1516.
  9. Knuppel, A., et al., Sugar intake from sweet food and beverages, common mental disorder and depression: prospective findings from the Whitehall II study. Sci Rep, 2017. 7(1): p. 6287.
  10. Sanchez-Villegas, A., et al., Fast-food and commercial baked goods consumption and the risk of depression. Public Health Nutr, 2012. 15(3): p. 424-32.
  11. Mantantzis, K., et al., Sugar rush or sugar crash? A meta-analysis of carbohydrate effects on mood. Neurosci Biobehav Rev, 2019. 101: p. 45-67.
  12. Salari-Moghaddam, A., et al., Adherence to the MIND diet and prevalence of psychological disorders in adults. J Affect Disord, 2019. 256: p. 96-102.
  13. Psaltopoulou, T., et al., Mediterranean diet, stroke, cognitive impairment, and depression: A meta-analysis. Ann Neurol, 2013. 74(4): p. 580-91.
  14. Li, Y., et al., Dietary patterns and depression risk: A meta-analysis. Psychiatry Res, 2017. 253: p. 373-382.
  15. Gibson-Smith, D., et al., Association of food groups with depression and anxiety disorders. Eur J Nutr, 2020. 59(2): p. 767-778.
  16. Egede, L.E. and C. Ellis, Diabetes and depression: global perspectives. Diabetes Res Clin Pract, 2010. 87(3): p. 302-12.
  17. Roy, T. and C.E. Lloyd, Epidemiology of depression and diabetes: a systematic review. J Affect Disord, 2012. 142 Suppl: p. S8-21.
  18. Reis, D.J., et al., The depressogenic potential of added dietary sugars. Med Hypotheses, 2020. 134: p. 109421.
  19. Della Corte, K.W., et al., Effect of Dietary Sugar Intake on Biomarkers of Subclinical Inflammation: A Systematic Review and Meta-Analysis of Intervention Studies. Nutrients, 2018. 10(5).
  20. Ii Timberlake, M. and Y. Dwivedi, Linking unfolded protein response to inflammation and depression: potential pathologic and therapeutic implications. Mol Psychiatry, 2019. 24(7): p. 987-994.
  21. Berk, M., et al., So depression is an inflammatory disease, but where does the inflammation come from? BMC Med, 2013. 11: p. 200.
  22. Beurel, E., M. Toups, and C.B. Nemeroff, The Bidirectional Relationship of Depression and Inflammation: Double Trouble. Neuron, 2020. 107(2): p. 234-256.
  23. Holford, P., Depression: the nutrition connection. Primary Care Mental Health, 2003. 1: p. 9-16.
  24. Mikkelsen, K., L. Stojanovska, and V. Apostolopoulos, The Effects of Vitamin B in Depression. Curr Med Chem, 2016. 23(38): p. 4317-4337.
  25. Fava, M., et al., Folate, vitamin B12 and homocysteine in major depressive disorder. American Journal of Psychiatry, 1997. 254: p. 426-8.
  26. Sangle, P., et al., Vitamin B12 Supplementation: Preventing Onset and Improving Prognosis of Depression. Cureus, 2020. 12(10): p. e11169.
  27. Lin, C.C. and T.L. Huang, Brain-derived neurotrophic factor and mental disorders. Biomed J, 2020. 43(2): p. 134-142.
  28. Molteni, R., et al., A high-fat, refined sugar diet reduces hippocampal brain-derived neurotrophic factor, neuronal plasticity, and learning. Neuroscience, 2002. 112(4): p. 803-14.
  29. Marosi, K. and M.P. Mattson, BDNF mediates adaptive brain and body responses to energetic challenges. Trends Endocrinol Metab, 2014. 25(2): p. 89-98.
  30. Sellmann, C., et al., Diets rich in fructose, fat or fructose and fat alter intestinal barrier function and lead to the development of nonalcoholic fatty liver disease over time. J Nutr Biochem, 2015. 26(11): p. 1183-92.
  31. Piya, M.K., A.L. Harte, and P.G. McTernan, Metabolic endotoxaemia: is it more than just a gut feeling? Curr Opin Lipidol, 2013. 24(1): p. 78-85.
  32. Thuy, S., et al., Nonalcoholic fatty liver disease in humans is associated with increased plasma endotoxin and plasminogen activator inhibitor 1 concentrations and with fructose intake. J Nutr, 2008. 138(8): p. 1452-5.
  33. Jiang, H., et al., Altered fecal microbiota composition in patients with major depressive disorder. Brain Behav Immun, 2015. 48: p. 186-94.
  34. Huang, R., K. Wang, and J. Hu, Effect of Probiotics on Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients, 2016. 8(8).
  35. Stice, E., K.S. Burger, and S. Yokum, Relative ability of fat and sugar tastes to activate reward, gustatory, and somatosensory regions. Am J Clin Nutr, 2013. 98(6): p. 1377-84.
  36. Colantuoni, C., et al., Excessive sugar intake alters binding to dopamine and mu-opioid receptors in the brain. Neuroreport, 2001. 12(16): p. 3549-52.
  37. Grace, A.A., Dysregulation of the dopamine system in the pathophysiology of schizophrenia and depression. Nat Rev Neurosci, 2016. 17(8): p. 524-32.
  38. Black, C.N., et al., Is depression associated with increased oxidative stress? A systematic review and meta-analysis. Psychoneuroendocrinology, 2015. 51: p. 164-75.
  39. Choi, H.J., et al., Effect of glucose ingestion in plasma markers of inflammation and oxidative stress: analysis of 16 plasma markers from oral glucose tolerance test samples of normal and diabetic patients. Diabetes Res Clin Pract, 2013. 99(2): p. e27-31.
  40. Yamagata, A.S., et al., Selfish brain and selfish immune system interplay: A theoretical framework for metabolic comorbidities of mood disorders. Neurosci Biobehav Rev, 2017. 72: p. 43-49.
  41. Hamer, J.A., et al., Brain insulin resistance: A treatment target for cognitive impairment and anhedonia in depression. Exp Neurol, 2019. 315: p. 1-8.
  42. Kan, C., et al., A systematic review and meta-analysis of the association between depression and insulin resistance. Diabetes Care, 2013. 36(2): p. 480-9.
  43. Lecoultre, V., et al., Effects of fructose and glucose overfeeding on hepatic insulin sensitivity and intrahepatic lipids in healthy humans. Obesity (Silver Spring), 2013. 21(4): p. 782-5.
  44. Aragno, M. and R. Mastrocola, Dietary Sugars and Endogenous Formation of Advanced Glycation Endproducts: Emerging Mechanisms of Disease. Nutrients, 2017. 9(4).
  45. Li, J., et al., Advanced glycation end products and neurodegenerative diseases: mechanisms and perspective. J Neurol Sci, 2012. 317(1-2): p. 1-5.
  46. Van Puyvelde, K., et al., Effect of advanced glycation end product intake on inflammation and aging: a systematic review. Nutr Rev, 2014. 72(10): p. 638-50.
  47. van Dooren, F.E., et al., Advanced Glycation End Product (AGE) Accumulation in the Skin is Associated with Depression: The Maastricht Study. Depress Anxiety, 2017. 34(1): p. 59-67.

 

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