The Sandpile of Health

In previous posts I have attempted to develop the idea of a perpetual slight instability (or ‘relaxed static stability’) at the core of life, which enables us to quickly adapt to and survive changes in the outside world. This manifests inter alia in the intrinsic variability of rhythm in the healthy heart, the vasomotor fluxes that compensate for changes in position or workload, the shifting rhythm waves that ebb and flow through our capillary beds, and the neuromuscular juggling act of remaining upright.

We must be resilient and able to adapt when required, but the changes we make are at the same time softened by continuity. We remain recognizably ourselves through the vicissitudes of life until one or more limits are exceeded, we reach a biological event horizon and depart. Countering, complementing and integrating into that necessary instability, therefore, we possess equally necessary multiple buffering systems.

These range from the chemical (pH continuity in the blood) and the physicochemical (blood-brain barrier, placenta), to the prohomeostatic damage-responsive generation of palmitoylethanolamide in our tissues (1, 2), our multiple host defenses against cancer (3), the metabolomic modularity characteristic of omnivores (4), the multi-buffering capacity of mast cells (5) and the constantly flickering epigenetic responses (6) that allow us to survive with an inherited and consolidated gene set while circumstances around and inside us change.

These buffers brought us safely out of Africa – or Asia (7, 8) – and kept us going for the first raw 200,000 years. In today’s cooked (over-cooked?) environment, however, many of these buffers are approaching or arriving at the point of failure; not only in individuals, but also collectively.

We see this in the rising tides of so many of the chronic degenerative diseases (9-11). We see it also in the increasing numbers of individuals presenting with malnutrition (12) and related multiple disease states (13), together with the subsequent growth of polypharmacy (14), iatrogenic hospitalisations (15, 16) and, probably, overall deaths (17). The industrial diet appears to be a significant cause of these negative changes (12), with particularly steep increases in multimorbidity emerging in the ultra-processed USA (18) and UK (19).

The decline in our public health is both chaotic and catastrophic, and I use those terms deliberately.

I have long been fascinated by chaos and catastrophe theories, and the point where chaos flips to catastrophe, because I think they can teach us about health and the fraying and final collapse of health into disease, dying and death.

In 1965 I attended a talk given by Jacques Monod at the University of Edinburgh – the easier, public lecture, natch – in which he discussed randomness, an early sub-species of chaos theory, and its involvement in the unpredictability of evolution. My geneticist dad dragged me to this one.

Years later, while I was a student at that same university, I caught Christopher Zeeman’s RI Christmas lecture on TV and became obsessed with Rene Thom’s conceptual model of the weight suspended by multiple threads. In this model, threads break slowly and chaotically until eventually, as the load is born by a diminishing number of threads, and enough bifurcation points have been passed, the process moves into asymptotic/catastrophic mode and the weight crashes to the ground. I couldn’t follow the math but I could, almost, understand the example.

Mark Buchanan’s illuminating 2000 book ‘Ubiquity, Why Catastrophes Happen’, made it easier. He described the famous sandpile experiment (18), which used a computer model to analyze how gradual small inputs into a complex system ie dropping grains of sand onto a sandpile, would eventually trigger a collapse, or avalanche.

Most collapses were relatively small but every now and then a major landslide occurred, demolishing a large part of the whole structure. This may bring back half-forgotten memories from long-gone days at the beach. One of the key findings was that the effect of any single grain was completely unpredictable.

Quoting, selectively, from Buchanan’s book:

“To find out why such unpredictability should show up in their sandpile, the scientists played a trick with their computer. Imagine peering down on the pile from above and coloring it in according to its steepness. Where it is relatively flat and stable, color it green; where steep and, in avalanche terms, “ready to go,” color it red. They found that at the outset, the pile looked mostly green, but that, as the pile grew, the green became infiltrated with ever more red. With more grains, the scattering of red danger spots grew until a dense skeleton of instability ran through the pile. Here was a clue to its peculiar behavior: a grain falling on a red spot can, by domino-like action, cause sliding at other nearby red spots.

“If the red network was sparse, and all trouble spots were well isolated one from the other, then a single grain could have only limited repercussions. But when the red spots come to riddle the pile, the consequences of the next grain become unpredictable. It might trigger only a few tumblings, or it might instead set off a cataclysmic chain reaction involving millions. The sandpile had acquired a hypersensitive and peculiarly unstable condition in which the next falling grain could trigger a response of any size whatsoever.”

I think this is directly applicable to health and nutrition. We are sentient sandpiles, and the nutritional impoverishment of our age has multiplied our red spots of vulnerability (ie 21).

There are various lines of clinical evidence that support the sandpile concept.

It is obvious that most chronic degenerative diseases are increasing in frequency, and decreasing in latency. To complicate matters, some of these conditions appear to selectively increase the risk of developing others.

In some cases plausible mechanistic explanations have been identified, such as CKD and diabetes predisposing to cardiovascular disease via carbamylative, glycemic and inflammatory stress (22, 23). Another example is impaired mineral absorption and increased bone resorption, driven by inflammatory bowel disease, which increases the risk of osteoporosis (24). Having said that, there are likely multiple mechanisms involved here, as the microbiota impact on bone via many routes (24, 25).

In other cases the links are more obscure, at least to me. How does breast cancer raise the risk of coronary heart disease (26)? The cardiotoxic effects of cancer treatments may be involved, and there may be shared risk factors for both pathologies, but is that the whole story? In yet other cases, apparent associations between pathologies most likely center around a shared aetiology (27).

Within this limited thesis, the nature of the links doesn’t matter. Multimorbidity and its attendant polypharmacy confer, inevitably, a significantly increasing risk of death (28-31/32). The asymptomatic drifts towards the asymptotic. By that, I mean that the chaotic progression from pre-clinical and often reversible pathology through to irreversible stages is followed by a catastrophic collapse of health (associated with rapidly rising treatment costs) and a final exponential approach towards death.

Examples of this final rush to the event horizon include the rising crescendo of failing trabeculae that culminates in osteoporotic fracture, the slow growth of atheroma that accelerates into the rupture that precipitates infarct, or the rapidly progressing loss of anti-arrhythmic control. We go medically bankrupt in two ways; gradually, then suddenly.

A similar pattern manifests in the way that risk factors increasingly predict premature death. Early life adversity, smoking, excessive alcohol consumption, physical inactivity, hypertension, obesity, and high levels of triglycerides and low-density lipoprotein cholesterol (LDL-C), constitute a cluster of overlapping risk factors that combine to produce generally supra-additive and, in some cases, multiplicative risk of coronary heart disease and other forms of death (28-33).

The degree of supra-additive and multiplicative risk is exacerbated by socioeconomic factors (29, 33). As our ‘elites’ drive the West into depression, therefore, public health will fall further and faster as we move closer, in a chaotic manner, towards social catastrophe. This is a pattern last seen when Professor Jeffrey Sachs and colleagues administered ‘shock therapy’ to Russia in the early ’90s (34). Much of the subsequent major decline in public health was caused by Western governments withholding critical support (35); Sachs for his part was and is a man of high intelligence and integrity (36).

All of the above constitutes yet another argument for establishing prevention as the first level of the next-gen model of public health, with early detection and the treatment of pre-clinical disease as a second level. Drugs have little application here; in asymptomatic individuals, therapeutic indices and cost are obviously paramount. This makes nutrition and test-based pharmaconutrition the tools of choice in the first and second levels.

Pharmaceutical medicine is not dead, nor will it die, but it should be put in its proper place. For historical, financial and political reasons it is currently used as a blanket first-level approach, and to paper over the fractures generated in individual and public bodies by poor nutritional baselines. In a more rational world it would be primarily retained as a third-level safety net for those who fail the first two stages.

Ozempic and its relatives are a case in point. The medical establishment and their pharma bros continue to find new indications for these drugs, ranging from addiction management to cancer risk reduction. This pharmaceutical holding strategy continues to extend the fingers of instability, creating further and potentially more serious problems further ahead (37). The obvious cure – obvious to all but the usual vested interests – is to put down the syringes, and re-design the food universe.

Increasing numbers of doctors understand that the many fingers of instability in the prevailing socioeconomic and medical models are over-extended, and that we have entered a critical state. Unexpectedly, however, the imminent catastrophic change could be a positive one; thanks in no small measure to Robert Kennedy Jr, the wind is shifting into the right quarter, and we may still avoid the sandbanks of healthcare bankruptcy.

The future, however, is a foreign country, and excess mortality (mortality above the non-crisis mortality rate in the population of interest), has been running at around 10% since the mRNA shots were mandated (38, 39). This is occurring on top of a previously projected steep global decline (40), and if sustained will halve world population by 2031. The sands themselves may be running out.

Next week: How do I love thee? Let me count the ways.

References

1. Esposito E, Cuzzocre S. Palmitoylethanolamide in homeostatic and traumatic central nervous system injuries. CNS Neurol. Disord. Drug Targets. 2013;12:55–61.
2. Gugliandolo E, Peritore AF, Piras C, Cuzzocrea S, Crupi R. Palmitoylethanolamide and Related ALIAmides: Prohomeostatic Lipid Compounds for Animal Health and Wellbeing. Vet Sci. 2020 Jun 16;7(2):78.
3. https://whitesmoke-heron-286383.hostingersite.com/blog/phoenix-rising/
4. Gómez-Romero L, López-Reyes K, Hernández-Lemus E. The Large-Scale Structure of Human Metabolism Reveals Resilience via Extensive Signaling Crosstalk. Front Physiol. 2020 Dec 16;11:588012.
5. https://whitesmoke-heron-286383.hostingersite.com/blog/tied-to-the-mast/
6. O’Dea RE, Noble DWA, Johnson SL, Hesselson D, Nakagawa S. The role of non-genetic inheritance in evolutionary rescue: epigenetic buffering, heritable bet hedging and epigenetic traps. Environ Epigenet. 2016 Feb 15;2(1):dvv014. 
7. Chaimanee Y, Chavasseau O, Beard KC, Kyaw AA, Soe AN, Sein C, Lazzari V, Marivaux L, Marandat B, Swe M, Rugbumrung M, Lwin T, Valentin X, Zin-Maung-Maung-Thein, Jaeger JJ. Late Middle Eocene primate from Myanmar and the initial anthropoid colonization of Africa. Proc Natl Acad Sci U S A. 2012 Jun 26;109(26):10293-7. 
8. Chaimanee Y, Chavasseau O, Lazzari V, Soe AN, Sein C, Jaeger JJ. Early anthropoid primates: New data and new questions. Evol Anthropol. 2024 Jun;33(3):e22022.
9. The national health survey 1935-1936: significance, scope and method of a nation-wide family canvass of sickness in relation to its social and economic setting, preliminary reports. Generated by the United States Division of Public Health Methods, Washington 1938
10. Cumming HS. “Chronic Disease as a Public Health Problem,” Milbank Memorial Fund Quarterly 14, no. 2 (1936): 125–131, 127.
11. CDC (2024), Managing Chronic Health Conditions.
12. Sandal M. ESPEN 2024 – Malnutrizione: un’emergenza europea per anziani e malati. Univadis. https://www.univadis.it/viewarticle/espen-2024-malnutrizione-emergenza-europea-anziani-e-malati-2024a1000gm2
13. Boersma P, Black LI, Ward BW. Prevalence of Multiple Chronic Conditions Among US Adults, 2018. Prev Chronic Dis. 2020 Sep 17;17:E106.
14. Saljoughian M. Polypharmacy and Drug Adherence in Elderly Patients. US Pharm. 2019;44(7):33-36.
15. Pirmohamed M, James S, Meakin S, Green C, Scott AK, Walley TJ, Farrar K, Park BK, Breckenridge AM. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ. 2004 Jul 3;329(7456):15-9. 
16. Osanlou R, Walker L, Hughes DA, Burnside G, Pirmohamed M. Adverse drug reactions, multimorbidity and polypharmacy: a prospective analysis of 1 month of medical admissions. BMJ Open. 2022 Jul 4;12(7):e055551.
17. GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015 Jan 10;385(9963):117-71.
18. King DE, Xiang J, Pilkerton CS. Multimorbidity Trends in United States Adults, 1988-2014. J Am Board Fam Med. 2018 Jul-Aug;31(4):503-513. 
19. Singer L, Green M, Rowe F, Ben-Shlomo Y, Kulu H, Morrissey K. Trends in multimorbidity, complex multimorbidity and multiple functional limitations in the ageing population of England, 2002-2015. J Comorb. 2019 Sep 4;9:2235042X19872030.
20. Bak P, Tang C, Wiesenfeld K. Self-organized criticality. Phys Rev A Gen Phys. 1988 Jul 1;38(1):364-374.
21. https://whitesmoke-heron-286383.hostingersite.com/blog/the-new-vulnerability/
22. https://whitesmoke-heron-286383.hostingersite.com/blog/dry-spell/
23. https://newsroom.heart.org/news/heart-disease-could-hit-up-to-28-years-sooner-for-people-with-ckm-syndrome
24. Wei H, Zhao Y, Xiang L. Bone health in inflammatory bowel disease. Expert Rev Gastroenterol Hepatol. 2023 Jul-Dec;17(9):921-935.
25. Chen Y, Wang X, Zhang C, Liu Z, Li C, Ren Z. Gut Microbiota and Bone Diseases: A Growing Partnership. Front Microbiol. 2022 May 6;13:877776.
26. Dai L, Li R, Hao Q, Bao Y, Hu L, Zhang Y, Kang H, Wu H, Ma X, Song Y. Breast cancer is associated with coronary heart disease: a cross-sectional survey of NHANES 1999-2018. Front Cardiovasc Med. 2023 Dec 6;10:1274976.
27. https://whitesmoke-heron-286383.hostingersite.com/blog/bones-brains-and-automobiles/
28. Voutilainen A, Brester C, Kolehmainen M, Tuomainen TP. Epidemiological analysis of coronary heart disease and its main risk factors: are their associations multiplicative, additive, or interactive? Ann Med. 2022 Dec;54(1):1500-1510. 
29. Mehta N, Preston S. Are major behavioral and sociodemographic risk factors for mortality additive or multiplicative in their effects? Soc Sci Med. 2016 Apr;154:93-9.
30. Vogeli C, Shields AE, Lee TA, Gibson TB, Marder WD, Weiss KB, Blumenthal D. Multiple chronic conditions: prevalence, health consequences, and implications for quality, care management, and costs. J Gen Intern Med. 2007 Dec;22 Suppl 3(Suppl 3):391-5. 
31. Lee TA, Pickard AS, Bartle B, Weiss KB. Osteoarthritis: a comorbid marker for longer life? Ann Epidemiol. 2007 May;17(5):380-4.
32. Cleveland RJ, Nelson AE, Callahan LF. Knee and hip osteoarthritis as predictors of premature death: a review of the evidence. Clin Exp Rheumatol. 2019 Sep-Oct;37 Suppl 120(5):24-30.
33. https://whitesmoke-heron-286383.hostingersite.com/blog/the-shadow-of-your-smile/
34. Notzon FC, Komarov YM, Ermakov SP, Sempos CT, Marks JS, Sempos EV. Causes of declining life expectancy in Russia. JAMA. 1998 Mar 11;279(10):793-800. 
35. https://www.npr.org/transcripts/1097135961
36. https://www.youtube.com/watch?v=bYQ8FI2UhDM
37. https://whitesmoke-heron-286383.hostingersite.com/blog/an-exercise-in-bureaucracy/
38. Dowd E, Becker G, Kennedy RF Jr. “Cause Unknown”: The Epidemic of Sudden Deaths in 2021 & 2022 & 2023 (Children’s Health Defense). https://www.amazon.com/gp/aw/d/1648210732/ref=dp_ob_neva_mobile
39. Degtiareva E, Tilstra AM, Schöley J, Kashyap R, Dowd JB. Cause-Specific Excess Mortality in the US During the COVID-19 Pandemic. medRxiv BMJ Yale. doi: https://doi.org/10.1101/2024.03.05.24303783
40. Vollset SE, Goren E, Yuan C-W and 21 other authors. Fertility, mortality, migration, and population scenarios for 195 countries and territories from 2017 to 2100: a forecasting analysis for the Global Burden of Disease Study.  Lancet 2020 Jul 14;S0140-6736(20)30677-2.