Hothead

Would you kill for a burger, fries and a shake?

Today’s lifestyle promotes dysbiosis, endotoxemia, systemic chronic inflammatory stress, and metabolic disorders. All of these fan the slow-burning fires of neuroinflammation (1-4).

Neuroinflammation in the hypothalamus, hippocampus, and other parts of the brain is a pivotal link between negative elements in our exposome such as the modern diet (5-7), social stress (8,9), a sedentary lifestyle (10, probably!), and a whole range of brain-related pathologies.

These include anxiety (11, 12), depression (12, 13), reduced impulse control (14), impaired memory (15), and autonomic dysfunction (16) – which may feed negatively back to neuroinflammation via colonic/dysbiotic mechanisms (16) – and a heightened risk, over the longer term, of Parkinsonism and Alzheimer’s disease (17, 18).

Chronic neuroinflammatory stress kills neurons via programmed cell death routes, some of which are inherently progressive (19), and damages supra-neuronal organization via degradation of the extracellular matrix (20). It increases the neurotoxicity of pharmaceutical and environmental toxins (21), contributing further to increased neuronal damage and loss.

It is also now persuasively linked to our growing weight problem, with a vicious circle apparently operating between obesity, increased hypothalamic neuroinflammation, and disturbed appetite control (22-24). A diet high in sugars and fats will do this (25, 26), and is centrally involved in food addiction (27-29); constituting a feed-forward loop {{{neuro-inflammation encourages over-eating and obesity (23) which drives neuro-inflammation (23)}}}, that food companies love to feed into.

The modern, ultra-processed diet is at the center of this mess. It is strongly associated with obesity (30, 31), inflammation/neuroinflammation (32, 33), and reduced hippocampal neurogenesis and size (34-35). It is also linked to cognitive decline (36, 37) and, mechanistically, to neurodegenerative diseases (38).

If consumed during pregnancy it likely causes permanent changes in the hypothalamus of the developing fetus (39, 40), creating permanently altered feeding behaviors and adding to our growing epigenetic burden (ie 41).

There is widespread agreement that the modern diet kills many of us, albeit slowly (42). The plot, however, thickens. New evidence indicates that it may be killing increasing numbers of us quickly as well.

In the USA and the UK, the two leading nations in terms of ultra-processed food consumption, both domestic and non-domestic violent crimes have been increasing for at least a decade (43, 44), with a recent up-tick driven by idiotic Covid-19 policies (45-47).

Anti-social behavior is not exclusively due to what we eat; the decline in communality driven by neo-liberalism is probably just as important (48). Nevertheless, an interesting link is emerging between ultra-processed foods, and the old ultraviolence (49).

Do you feel we are seeing more and more road rage, air rage, queue rage, and computer rage (aka desk rage)? Lügenpresse such as the Daily Mail (50) or the Economist (51) cover these stories differently, but the increasing frequency of rage incidents (52, 53) (and anxiety, and depression) suggests that something is going acutely wrong with our brains.

This is reflected in the hallowed Diagnostic and Statistical Manual of Mental Disorders. Impulsive, pathological aggression was first identified/labeled in the 4th edition as Intermittent Explosive Disorder, conveniently abbreviated as IED. The latest (5th) edition includes an entire section on this condition, which if broadly defined is now estimated to affect as many as 7% of Americans (54).

If more conservative definitions of IED are used, ie behavior to the point that interferes with the individual’s work, social life, or relationships, the incidence drops below 3% (55). It is the more severe forms of IED that make the headlines and the crime statistics, but if these are increasing then the less severe forms are likely affecting more of us as well.

The search for causative factors behind this unhappy trend has reached a standoff.

Genes may be involved such as those associated with dopaminergic chemistry (ie 56), but they have not been clearly or consistently defined, and are not increasing in the population. Nurture is also in the frame; bad parenting with childhood exposure to trauma appears to be a distinct risk factor (57), and the combination of bad genes and bad parenting may have supra-additive effects.

There appear to be changes in brain structures, at least in some cases (58), which might be caused by genes and/or by formative experiences. They may also be driven by environmental factors, and the increasing number of reported rage episodes suggests an incoming tide.

A recent rage variant, fast food rage, provides a possible clue. My favorite example; a young woman dressed as the Cookie Monster who ran amok in a McDonalds… (59).

A fast and ultra-processed diet induces neuroinflammatory stress (31-33). We are eating more of these toxic foods, and it seems reasonable to propose that more of us are therefore experiencing more severe neuroinflammation. This likely makes us more prone to the overlapping behaviors of PTSD and violence (60, 61).

Neuroinflammation disrupts neuronal structure and function in many areas of the brain including the insular cortex (57), an area where changes have been found in IED patients (62). As this part of the brain is involved inter alia in monitoring and regulating emotions, risk prediction, decision-making, self-awareness, and complex social functions such as empathy, a loss of insular integrity might well contribute to uncontrolled rage.

It starts to look as if the modern diet is making us angry, and in the worst cases more likely to kill or be killed. It might even be contributing to the increasingly irrational and aggressive nature of American and British foreign policy.

Supporting evidence comes from research that showed raised inflammatory markers in the blood of IED subjects (63), in whom CRP and IL-6 levels correlated surprisingly well with the frequency of their aggressive behavior; and a more recent and much larger study that found a consistent correlation between incidents of violence and diseases with a significant inflammatory component (64).

This last paper is a very nuanced piece of research with profound socioeconomic implications and is worth reading in full. It is in line with patterns of different consumption of fast and ultra-processed foods in different ethnic and socioeconomic groups (65-69), increased impulsivity associated with consuming those foods (70 – although see also 71), and rates of aggressive and criminal behavior in those groups (72).

Overall, these findings suggest that the food industry is helping to create an increasingly aggressive and divided society.If this makes you feel anger, that is a rational response. But when you see folk flaring up over trivia, it may be due to neuroinflammation raising the temperature inside their heads.

If you are mad as hell and unwilling to take this anymore (73), step away from the Doritos, and the Dorito-flavoured vodka too (74).

Instead, learn how to cook. The venerable Moosewood Cookbook, for example, uses ingredients that provide plenty of prebiotic fibers and polyphenols, thereby reducing dysbiosis, chronic inflammation, and neuroinflammation. They’re easy to follow, and the results taste good.

If you can’t stand the heat, get into the kitchen.

Next week: Self-destruction

References:

1. Kurita N, Yamashiro K, Kuroki T, Tanaka R, Urabe T, Ueno Y, Miyamoto N, Takanashi M, Shimura H, Inaba T, Yamashiro Y, Nomoto K, Matsumoto S, Takahashi T, Tsuji H, Asahara T, Hattori N. Metabolic endotoxemia promotes neuroinflammation after focal cerebral ischemia. J Cereb Blood Flow Metab.
2020 Dec;40(12):2505-2520.
2. Stubbs DJ, Yamamoto AK, Menon DK. Imaging in sepsis-associated encephalopathy—Insights and opportunities. Nat. Rev. Neurol. 2013, 9, 551–561.
3. Heming N, Mazeraud A, Verdonk F, Bozza FA, Chrétien F, Sharshar T. Neuroanatomy of sepsis-associated encephalopathy. Crit Care. 2017 Mar 21;21(1):65.
4. Vargas-Soria M, García-Alloza M, Corraliza-Gómez M. Effects of diabetes on microglial physiology: a systematic review of in vitro, preclinical and clinical studies. J Neuroinflammation. 2023 Mar 3;20(1):57.
5. Ávalos Y, Kerr B, Maliqueo M, Dorfman M. Cell and molecular mechanisms behind diet-induced hypothalamic inflammation and obesity. J Neuroendocrinol 2018 Oct;30(10):e12598.
6. Thaler JP, Yi CX, Schur EA, Guyenet SJ, Hwang BH, Dietrich MO, Zhao X, Sarruf DA, Izgur V, Maravilla KR, Nguyen HT, Fischer JD, Matsen ME, Wisse BE, Morton GJ, Horvath TL, Baskin DG, Tschöp MH, Schwartz MW. Obesity is associated with hypothalamic injury in rodents and humans. J Clin Invest. 2012
Jan;122(1):153-62.
7. D’Ambrosio C, Cigliano L, Mazzoli A, Matuozzo M, Nazzaro M, Scaloni A, Iossa S, Spagnuolo MS. Fructose Diet-Associated Molecular Alterations in Hypothalamus of Adolescent Rats: A Proteomic Approach. Nutrients. 2023 Jan 16;15(2):475.
8. Weber MD, Godbout JP, Sheridan JF. Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal. Neuropsychopharmacology. 2017 Jan;42(1):46-61.
9. https://drpaulclayton.eu/blog/social-defeat/
10. Lira FS, Yamashita AS, Rosa JC, Tavares FL, Caperuto E, Carnevali LC Jr, Pimentel GD, Santos RV, Batista ML Jr, Laviano A, Rossi-Fanelli F, Seelaender M. Hypothalamic inflammation is reversed by endurance training in anorectic-cachectic rats. Nutr Metab (Lond). 2011 Aug 24;8(1):60.
11. Hou R, Baldwin DS. (2012). A neuroimmunological perspective on anxiety disorders. Human Psychopharmacology, 27, 6–14.
12. Hovatta L, Juhila J,Donner J. (2011). Oxidative stress in anxiety and comorbid disorders. Neuroscience Research, 68, 261–275
13. Cernackova A, Durackova Z, Trebaticka J, Mravec B. Neuroinflammation and depressive disorder: The role of the hypothalamus. J Clin Neurosci. 2020 May;75:5-10.
14. Gassen J, Prokosch ML, Eimerbrink MJ, Proffitt Leyva RP, White JD, Peterman JL, Burgess A, Cheek DJ, Kreutzer A, Nicolas SC, Boehm GW, Hill SE. Inflammation Predicts Decision-Making Characterized by Impulsivity, Present Focus, and an Inability to Delay Gratification. Sci Rep. 2019 Mar 20;9(1):4928.
15. Pfau ML, Russo SJ. Neuroinflammation Regulates Cognitive Impairment in Socially Defeated Mice. Trends Neurosci. 2016 Jun;39(6):353-355.
16. Bellocchi C, Carandina A, Montinaro B, Targetti E, Furlan L, Rodrigues GD, Tobaldini E, Montano N. The Interplay between Autonomic Nervous System and Inflammation across Systemic Autoimmune Diseases. Int J Mol Sci. 2022 Feb 23;23(5):2449.
17. Chitnis T, Weiner HL. CNS inflammation and neurodegeneration. J Clin Invest. 2017 Oct 2;127(10):3577-3587.
18. https://drpaulclayton.eu/blog/controlled-flight-into-terrain/
19. Heckmann BL, Tummers B, Green DR. Crashing the computer: apoptosis vs. necroptosis in neuroinflammation. Cell Death Differ. 2019 Jan;26(1):41-52.
20. https://drpaulclayton.eu/blog/matrix-reloaded/
21. Ugalde-Muñiz P, Fetter-Pruneda I, Navarro L, García E, Chavarría A. Chronic Systemic Inflammation Exacerbates Neurotoxicity in a Parkinson's Disease Model. Oxid Med Cell Longev. 2020 Jan 13;2020:4807179.
22. Brown SSG, Westwater ML, Seidlitz J, Ziauddeen H, Fletcher PC. Hypothalamic volume is associated with body mass index. Neuroimage Clin. 2023;39:103478.
23. Jais A, Brüning JC. Hypothalamic inflammation in obesity and metabolic disease. J Clin Invest. 2017 Jan 3;127(1):24-32.
24. Dong GZ, Yang HJ, Jiao YW, Zhang QY, Ma Y, Zhu SM, Zhang LH, Zhang M, Yao T, Cao Y, Tang LM. Using quantitative imaging to determine the correlation between hypothalamic inflammation and anxiety and depression in young patients with obesity. Ann Palliat Med. 2021 Jul;10(7):8043-8050.
25. Jamar G, Ribeiro DA, Pisani LP. High-fat or high-sugar diets as trigger inflammation in the microbiota-gut-brain axis. Crit Rev Food Sci Nutr. 2021;61(5):836-854.
26. Mota B, Ramos M, Marques SI, Silva A, Pereira PA, Madeira MD, Mateus N, Cardoso A. Effects of High-Fat and High-Fat High-Sugar Diets in the Anxiety, Learning and Memory, and in the Hippocampus Neurogenesis and Neuroinflammation of Aged Rats. Nutrients. 2023 Mar 11;15(6):1370.
27. Whatnall M, Clarke E, Collins CE, Pursey K, Burrows T. Ultra-processed food intakes associated with food addiction in young adults. Appetite. 2022 No 1;178:106260.
28. Lemos TC, Coutinho GMS, Silva LAA, Stariolo JB, Campagnoli RR, Oliveira L, Pereira MG, Mota BEF, Souza GGL, Canella DS, Khandpur N, David IA. Ultra-Processed Foods Elicit Higher Approach Motivation Than Unprocessed and Minimally Processed Foods. Front Public Health. 2022 Jun 21;10:891546.
29. Stevenson RJ, Francis HM, Attuquayefio T, Gupta D, Yeomans MR, Oaten MJ, Davidson T. Hippocampal-dependent appetitive control is impaired by experimental exposure to a Western-style diet. R Soc Open Sci. 2020 Feb 19;7(2):191338.
30. Askari M, Heshmati J, Shahinfar H, Tripathi N, Daneshzad E. Ultra-processed food and the risk of overweight and obesity: a systematic review and meta-analysis of observational studies Int. J. Obes 44 (10) (2020), 2080-2091
31. Moradi S, Entezari MH, Mohammadi H, Jayedi A, Lazaridi AV, Kermani MAH, Miraghajani M. Ultra-processed food consumption and adult obesity risk: a systematic review and dose-response meta-analysis. Crit Rev Food Sci Nutr. 2023;63(2):249-260.
32. Tristan Asensi M, Napoletano A, Sofi F, Dinu M. Low-Grade Inflammation and Ultra-Processed Foods Consumption: A Review. Nutrients. 2023 Mar 22;15(6):1546.
33. Solteni R, Barnard RJ, Ying Z, Roberts CK, Gómez-Pinilla F. A high-fat, refined sugar diet reduces hippocampal brain-derived neurotrophic factor, neuronal plasticity, and learning. Neuroscience. 2002; 112(4):803-14.
34. Freeman LR, Haley-Zitlin V, Rosenberger DS, Granholm AC. Damaging effects of a high-fat diet to the brain and cognition: a review of proposed mechanisms. Nutr Neurosci. 2014 Nov; 17(6):241-51.
35. Kanoski SE, Zhang Y, Zheng W, Davidson TL. The effects of a high-energy diet on hippocampal function and blood-brain barrier integrity in the rat. J Alzheimers Dis. 2010; 21(1):207-19.
36. Contreras-Rodriguez O, Reales-Moreno M, Fernández-Barrès S, Cimpean A, Arnoriaga-Rodríguez M, Puig J, Biarnés C, Motger-Albertí A, Cano M, Fernández-Real JM. Consumption of ultra-processed foods is associated with depression, mesocorticolimbic volume, and inflammation. J Affect Disord. 2023 Aug 15;335:340-348.
37. Gomes Gonçalves N, Vidal Ferreira N, Khandpur N, Martinez Steele E, Bertazzi Levy R, Andrade Lotufo P, Bensenor IM, Caramelli P, Alvim de Matos SM, Marchioni DM, Suemoto CK. Association Between Consumption of Ultra Processed Foods and Cognitive Decline. JAMA Neurol. 2023 Feb 1;80(2):142-150.
38. Kwon HS, Koh SH. Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes. Transl Neurodegener. 2020 Nov 26;9(1):42.
39. ilà-Gausch M, Ramírez S, Llana SR, Fos-Domènech J, Dropmann LM, Pozo M, et al. Maternal emulsifier consumption programs offspring metabolic and neuropsychological health. PLoS Biol. 2023; 21(8):e3002171.
40. Franssen D, Parent AS. Emulsifiers during gestation: The risks of ultra-processed food revealed in mice. PLoS Biol. 2023 Aug 25;21(8):e3002265.
41. Lecoutre S, Maqdasy S, Breton C. Maternal obesity as a risk factor for developing diabetes in offspring: An epigenetic point of view. World J Diabetes. 2021 Apr 15;12(4):366-382.
42. 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015 Dec 5;386(10010):2287-323.
43. Berk R. Is Violent Crime Increasing? U Penn Dept Criminology (2022). https://crim.sas.upenn.edu/fact-check/violent-crime-increasing
44. Number of police recorded violence against the person offences in England and Wales from 2002/03 to 2022/23. Clark D, Statista 2023. https://www.statista.com/statistics/288256/violent-crimes-in-england-and-
wales/#:~:text=Violent%20crimes%20in%20England%20and%20Wales%20increased%20to%20more%20than,just%20601%2C141%20violent%20crime%20offences.
45. Measuring the Shadow Pandemic: Violence against women during Covid-19. UN Women 2021
46. https://data.unwomen.org/sites/default/files/documents/Publications/Measuring-shadow-pandemic.pdf
47. Boserup B, McKenney M, Elkbuli A. Alarming trends in US domestic violence during the COVID-19 pandemic. Am J Emerg Med. 2020 Dec;38(12):2753-2755.
48. Navarro V. Neoliberalism as a class ideology; or, the political causes of the growth of inequalities. Int J Health Serv. 2007;37(1):47-62.
49. https://www.youtube.com/watch?v=T54uZPI4Z8A
50. https://www.dailymail.co.uk/news/article-12581361/motorist-banged-woman-driver-windscreen-road-rage-incident-unmasked.html
51. https://www.economist.com/gulliver/2016/05/11/resentment-of-first-class-passengers-can-be-a-cause-of-air-rage
52. https://www.forbes.com/sites/marisagarcia/2023/10/20/air-rage-is-getting-worse-and-airlines-cant-fix-it/
53. https://everytownresearch.org/reports-of-road-rage-shootings-are-on-the-rise/
54. Kessler RC, Coccaro EF, Fava M, Jaeger S, Jin R, Walters E. The prevalence and correlates of DSM-IV intermittent explosive disorder in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2006 Jun;63(6):669-78.
55. Scott KM, De Jonge P, Stein DJ and Kessler RC (eds) (2018) Mental Disorders Around the World: Facts and Figures From the WHO World Mental Health Surveys. Cambridge: Cambridge University Press.
56. Modestino EJ, Blum K, Dennen CA, Downs BW, Bagchi D, Llanos-Gomez L, Elman I,Baron D, Thanos PK, Badgaiyan RD, Braverman ER, Gupta A, Gold MS, Bowirrat A.Theorizing the Role of Dopaminergic Polymorphic Risk Alleles with Intermittent Explosive Disorder (IED), Violent/Aggressive Behavior and Addiction: Justification of Genetic Addiction Risk Severity (GARS) Testing. J Pers Med. 2022 Nov 23;12(12):1946.
57. Lee R, Meyerhoff J, Coccaro EF. Intermittent Explosive Disorder and aversive parental care. Psychiatry Res. 2014 Dec 15;220(1-2):477-82.
58. Seok JW, Cheong C. Gray Matter Deficits and Dysfunction in the Insula Among Individuals With Intermittent Explosive Disorder. Front Psychiatry. 2020 May 20;11:439.
59. https://wkfr.com/an-ohio-cookie-monster-attacked-a-mcdonalds-employees-on-video/
60. Shanazz K, Nalloor R, Lucas R, Vazdarjanova A. Neuroinflammation is a susceptibility factor in developing a PTSD-like phenotype. Front Behav Neurosci. 2023 Mar 29;17:1112837.
61. Paulino A, Kuja-Halkola R, Fazel S, Sariaslan A, Rietz ED, Lichtenstein P, Brikell I. Post-traumatic stress disorder and the risk of violent crime conviction in Sweden: a nationwide, register-based cohort study. Lancet Public Health. 2023 Jun;8(6):e432-e441.
62. Rolls A. Immunoception: the insular cortex perspective. Cell Mol Immunol. 2023 Nov;20(11):1270-1276.
63. Coccaro EF, Lee R, Coussons-Read M. Elevated plasma inflammatory markers in individuals with intermittent explosive disorder and correlation with aggression in humans. JAMA Psychiatry. 2014 Feb;71(2):158-65.
64. Castle R, Bushell WC, Mills PJ, Williams MA, Chopra D, Rindfleisch JA. Global Correlations Between Chronic Inflammation and Violent Incidents: Potential Behavioral Consequences of Inflammatory Illnesses Across Socio-Demographic Levels. Int J Gen Med. 2021 Oct 12;14:6677-6691.
65. Wang L, Martínez Steele E, Du M, Pomeranz JL, O'Connor LE, Herrick KA, Luo H, Zhang X, Mozaffarian D, Zhang FF. Trends in Consumption of Ultraprocessed Foods Among US Youths Aged 2-19 Years, 1999-2018. JAMA. 2021 Aug 10;326(6):519-
66. Costa BGGD, Duca GFD, Silva KSD, Benedet J, Malheiros LEA, Quadros EN, Streb AR, Rezende LFM. Socioeconomic inequalities in the consumption of minimally processed and ultra-processed foods in Brazilian adolescents. Cien Saude Colet. 2022 Apr;27(4):1469-1476. 530.
67. Organización Panamericana de la Salud. Organización Mundial de la Salud. Alimentos y Bebidas Ultraprocesados En América Latina: Tendencias, Efecto Sobre La Obesidad e Implicaciones Para Las Políticas Públicas. Departamento de Enfermedades no Transmisibles y Salud Mental; Washington, DC, USA: 2015.
68. Oviedo-Solís CI, Monterrubio-Flores EA, Cediel G, Denova-Gutiérrez E, Barquera S. Trend of Ultraprocessed Product Intake Is Associated with the Double Burden of Malnutrition in Mexican Children and Adolescents. Nutrients. 2022 Oct 17;14(20):4347.
69. https://drpaulclayton.eu/blog/eloi-and-morlocks/
70. Garza KB, Ding M, Owensby JK, Zizza CA. Impulsivity and Fast-Food Consumption: A Cross-Sectional Study among Working Adults. J Acad Nutr Diet. 2016 Jan;116(1):61-68.
71. Ruf A, Neubauer AB, Koch ED, Ebner-Priemer U, Reif A, Matura S.Microtemporal Dynamics of Dietary Intake, Physical Activity, and Impulsivity in Adult Attention-Deficit/Hyperactivity Disorder: Ecological Momentary Assessment Study Within Nutritional Psychiatry. JMIR Ment Health. 2023 Aug 17;10:e46550.
72. Morgan RE, Oudekerk BA. US Bureau of Justice Statistics, September 2019, NCJ 253043. Criminal Victimisation 2018. https://bjs.ojp.gov/content/pub/pdf/cv18.pdf
73. https://www.youtube.com/watch?v=ZwMVMbmQBug
74. https://us.empirical.co/products/doritos-x-empirical