Insult Me

Most insults can be disregarded. Some are so harmful that they must be countered if we are to survive; and I’ll talk about these further down the post. But a third group of insults are actually good for us, because they make us stronger (hat tip Friedrich Nietzsche).

Back in the day, my friends and I regularly encountered real life bullying at school. I still remember ‘your lunch money or your life’ threats in the corridors, fistfights behind the assembly hall, and grievous bodily harm on the rugby field. We coped, however, and grew stronger for it.

But Nietzsche seems to be dead, and there is clearly something wrong with today’s snowflake youth. Despite a proliferation of anti-bullying policies, our young folk are more vulnerable than ever; and when I read reports of children killing themselves because of cyber-bullying, I really wonder. Unkind and/or uninformed e-comments can easily be filtered out or switched off – so what’s their problem?

One part of the problem is today’s ultra-processed and truly terrible diet. Our children are eating food that undermines and unbalances their brains, making them less resilient and more prone to depression, poor self-worth and poor impulse control.

As a result too many of them are medicated, with worthless and damaging drugs that enable these small square pegs to be hammered into the small round holes of a terrible educational system, but do nothing to help them heal. Our kids have three strikes against them from the start, thanks to the criminals and sociopaths who run the food, pharmaceutical and educational industries.

This unhappy combination makes them less able to cope with the insults that life inevitably brings; insults that our bodies and brains must learn how to process and resolve in order to thrive, as the great Hungarian endocrinologist Hans Selye explained. His work and the science of adaptogens, now known as xeno-hormetics, teaches us that certain insults, or stressors, are essential to our wellbeing. These are the insults that up-regulate our many stress proteins (SP’s), which can be regarded as part of Selye’s resistance phase.

Under normal conditions the SP’s main function is to carry damaged proteins to the cell’s recycling bins (the proteasomes) for controlled destruction and amino acid re-use, and then help new, newly folded proteins to replace the old ones. In short, the stress proteins are specialised transporters or chaperones that play a key role in protein turnover, and cell and tissue maintenance.

Given the importance of this role, it is not surprising that many of the SP’s are up-regulated in the body when rates of tissue and protein damage increase. Blood and tissue levels of the different SP’s spike in response to a range of insults including exposure to extremes of temperature, infection, inflammation, oxidative stress, starvation, hypoxia; and they are an integral part of the processes of adaptation (to the insult) and healing – which involves, among other things, the resolution of inflammation.

This is how xeno-hormetics such as ginseng, withania or rhodiola work. They are interpreted by the body as minor insults, and trigger SP synthesis. Once levels of SP’s increase, the body’s ability to adapt, strengthen, resolve inflammation and heal is generally enhanced (1). Specifically, there is evidence that xeno-hormetics such as ashwagandha and rhodiola cause the up-regulation of some SP’s (2, 3) and that this contributes to subsequent improvements in mental and/or physical performance (4). 

Physical stressors can work in a similar way. The health benefits of saunas, for example, are generated via SP-up-regulation (5), and so are many if not most of the benefits of exercise. Physical stress causes an uptick in sestrins (6), a sub-set of the SP family, which leads to an interaction with AMP-Kinase (7) and subsequent improvement in muscle fitness (8). 

Nrf2 can be regarded as another SP, which is modulated in an inverse way by oxidative stress. Its normally short half-life is extended by oxidative stress, allowing it to accumulate and enter the cell nucleus where it triggers the up-regulation of multiple antioxidant systems (9, 10). 

If insults are persistently present in excess, however, to the point where they overwhelm even the body’s upgraded defences, they will inevitably lead to progressive damage and disease. (This is an example of Selye’s exhaustion phase.)

While recently snacking in the USA on what I thought was a relatively innocuous combination of savoury crackers, cheese dip and humus, I made the mistake of reading the contents labels on the packs. The cheese dip and the crackers were both full of high fructose corn syrup, which made them disgustingly sweet, and the humus was made not with olive oil (!), but corn oil.  

Three fundamentally healthy foods had been sabotaged by Big Phood. General Mills, Mars and Nestle had crammed enough sugar and omega 6 fatty acids into these products to make them no longer nutritious but toxic, and engineered to create malnutrition, chronic inflammation and mental dysfunction including poor impulse control and depression (11, 12). This is one major reason why life expectancy is falling in the USA and its vassal state the UK, the ever-increasing rates of suicide and why one in 8 Americans is now dependent on potentially dangerous combinations of psychotropic drugs (13).

How, I wondered, could these food companies justify such criminal behaviour? Are they deliberately trying to poison us? I’m withholding judgement on that one, but having met some of Big Phood’s most senior officials, it is clear that they hold consumers like us in deep contempt. Their foods (or more accurately fodder) are, collectively, a most insidious insult to us as individuals, as parents and as members of what used to be polite society.

But it is so hard to stop eating their junk. We are time-poor, often cash-poor too and the ultra-processed foods are cheap and widely available. And they taste so good. 

I have written previously how today’s mas-produced, ultra-processed foods are designed to be addictive, with fast-onset organoleptic rewards (sweet, salt, sour, crunch etc) that disguise their shoddy ingredients and lack of nutrients. Another problem is that their calorie density and excessive omega 6:3 ratios predispose us to obesity, chronic inflammation, disease and depression – which make us less decisive, less active. But now it seems that Big Phood’s Soma demotivates us too, even more directly.

Chronic inflammation in the body and brain triggers changes in the immune system which lead to profound changes in behaviour. Our natural response to sickness is to withdraw, reduce our activity levels, rest. This was originally designed to be an adaptative response to infection, encouraging us to use less energy to move around so that there was more available for the immune system to be activated, clear the infection and restore health. But now, thanks to our lifestyles and diets, we have low-level chronic inflammation almost all the time. And this is affecting our personalities, at a very profound level.

New research has revealed how this works. 

The inflammatory cytokines produced during chronic inflammation down-regulate the mesolimbic dopamine neurons so that they produce less dopamine. Lower dopamine levels decrease the motivation for work, by reducing the perception of reward while increasing the perception of effort involved (12, 14-17). So we become apathetic. We disengage, we shrug our shoulders, we complain but we settle for our mediocre, mendacious politicians. We go back to the supermarket and buy more junk because it is less trouble to eat their Soma, and feed it to our squalling, hyperactive and malnourished children.

This same diet is lacking in the nutrients required to support resilience, and so we break more easily and opt for easier solutions – as do our kids. What we should all be doing is moving towards a more Mediterranean diet (18, 19); or, at the very least, consuming more polyphenols and carotenoids of the kind found in saffron (20-25).

You could go on buying the new, improved Soylent Green from Nestle, General Mills or PepsiCo. It’s an insult to us all, and our children are especially vulnerable. Or, you could stop eating ultra-processed foods, starve the corporate beasts and go back to culinary basics. It’s hard to start this process, I know. But once you start feeding your brain what it needs, everything gets easier. 

REFERENCES

1. Heat-shock proteins induce T-cell regulation of chronic inflammation. van Eden W, van der Zee R, Prakken B. Nat Rev Immunol. 2005 Apr;5(4):318-30.

2. Leong PK, Chen N, Chiu PY, Leung HY, Ma CW, Tang QT, Ko KM. Long-term treatment with shengmai san-derived herbal supplement (Wei Kang Su) enhances antioxidant response in various tissues of rats with protection against carbon tetrachloride hepatotoxicity. J Med Food. 2010 Apr;13(2):427-38. doi: 10.1089/jmf.2009.1296.

3. Hernández-Santana A, Pérez-López V, Zubeldia JM, Jiménez-del-Rio M. A Rhodiola rosea root extract protects skeletal muscle cells against chemically induced oxidative stress by modulating heat shock protein 70 (HSP70) expression. Phytother Res. 2014 Apr;28(4):623-8.

4. Panossian A, Wikman G. Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress—Protective Activity. Pharmaceuticals (Basel). 2010 Jan; 3(1): 188–224.

5. .Garolla A, Torino M, Sartini B, Cosci I, Patassini C, Carraro U, Foresta C. Seminal and molecular evidence that sauna exposure affects human spermatogenesis. Hum Reprod. 2013 Apr;28(4):877-85.

6. Lenhare L, Crisol BM, Silva VRR, Katashima CK, Cordeiro AV, Pereira KD, Luchessi AD, da Silva ASR, Cintra DE, Moura LP, Pauli JR, Ropelle ER. Physical exercise increases Sestrin 2 protein levels and induces autophagy in the skeletal muscle of old mice. Exp Gerontol. 2017 Oct 15;97:17-21.

7. Wang T, Niu Y, Liu S, Yuan H, Liu X, Fu L. Exercise improves glucose uptake in murine myotubes through the AMPKα2-mediated induction of Sestrins. Biochim Biophys Acta Mol Basis Dis. 2018 Oct;1864(10):3368-3377.

8. Liu X, Niu Y, Yuan H, Huang J, Fu L. AMPK binds to Sestrins and mediates the effect of exercise to increase insulin-sensitivity through autophagy. Metabolism. 2015 Jun; 64(6):658-65.

9. Dinkova-Kostova AT, Talalay P. Direct and indirect antioxidant properties of inducers of cytoprotective proteins. Mol Nutr Food Res 2008;52 Suppl 1:S128–S138. 

10. Tebay LE, Robertson H, Durant ST, Vitale SR, Penning TM, Dinkova-Kostova AT et al. Mechanisms of activation of the transcription factor Nrf2 by redox stressors, nutrient cues, and energy status and the pathways through which it attenuates degenerative disease. Free Radic Biol Med 2015;88:108–46. 

11. Darcey VL, McQuaid GA, Fishbein DH, VanMeter JW. Dietary Long-Chain Omega-3 Fatty Acids Are Related to Impulse Controland Anterior Cingulate Function in Adolescents. Front Neurosci. 2019 Jan 9;12:1012.

12. Treadway M, Cooper JA, Miller AH. Can’t or won’t? Immunometabolic constraints on dopaminergic drive. Trends in Cognitive Sciences 2019, May 1, 435-448 (Review)

13. Moore TJ, Mattison DR. Adult Utilization of Psychiatric Drugs and Differences by Sex, Age, and Race. JAMA Intern Med. 2017 Feb 1;177(2):274-275.

14. Felger JC, Treadway MT. Inflammation Effects on Motivation and Motor Activity: Role of Dopamine. Neuropsychopharmacology. 2017 Jan;42(1):216-241. 

15. Felger JC. The Role of Dopamine in Inflammation-Associated Depression: Mechanisms and Therapeutic Implications. Curr Top Behav Neurosci. 2017;31:199-219.

16. Felger JC, Li Z, Haroon E, Woolwine BJ, Jung MY, Hu X, Miller AH. Inflammation is associated with decreased functional connectivity within corticostriatal reward circuitry in depression. Mol Psychiatry. 2016 Oct; 21(10):1358-65.

17. Furuyashiki T, Kitaoka S. Neural mechanisms underlying adaptive and maladaptive consequences of stress: roles of dopaminergic and inflammatory responses. Psychiatry Clin Neurosci. 2019 Jun 19. doi: 10.1111/pcn.12901. [Epub ahead of print] Review.

18. Bonaccio M, Di Castelnuovo A, Costanzo S, Pounis G, Persichillo M, Cerletti C, Donati MB, de Gaetano G, Iacoviello L. Mediterranean-type diet is associated with higher psychological resilience in a general adult population: findings from the Moli-sani study. Eur J Clin Nutr. 2018 Jan;72(1):154-160.

19. Frolinger T, Sims S, Smith C, Wang J, Cheng H, Faith J, Ho L, Hao K, Pasinetti GM. The gut microbiota composition affects dietary polyphenols-mediated cognitive resilience in mice by modulating the bioavailability of phenolic acids. Sci Rep. 2019 Mar 5;9(1):3546.

20. Aubry AV, Khandaker H, Ravenelle R, Grunfeld IS, Bonnefil V, Chan KL, Cathomas F, Liu J, Schafe GE, Burghardt NS. A diet enriched with curcumin promotes resilience to chronic social defeat stress. Neuropsychopharmacology. 2019 Mar;44(4):733-742.

21. Frolinger T, Smith C, Cobo CF, Sims S, Brathwaite J, de Boer S, Huang J, Pasinetti GM. Dietary polyphenols promote resilience against sleep deprivation-induced cognitive impairment by activating protein translation. FASEB J. 2018 Oct;32(10):5390-5404.

22. Blaze J, Wang J, Ho L, Mendelev N, Haghighi F, Pasinetti GM. Polyphenolic Compounds Alter Stress-Induced Patterns of Global DNA Methylation in Brain and Blood. Mol Nutr Food Res. 2018 Apr;62(8):e1700722.

23. Ward L, Pasinetti GM. Recommendations for Development of Botanical Polyphenols as “Natural Drugs” for Promotion of Resilience Against Stress-Induced Depression and Cognitive Impairment. Neuromolecular Med. 2016 Sep;18(3):487-95.

24. Dubner L, Wang J, Ho L, Ward L, Pasinetti GM. Recommendations for Development of New Standardized Forms of Cocoa Breeds and Cocoa Extract Processing for the Prevention of Alzheimer’s Disease: Role of Cocoa in Promotion of Cognitive Resilience and Healthy Brain Aging. J Alzheimers Dis. 2015;48(4):879-89.

25. Affron. Personal experience.