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Everything in moderation or moderating everything? Nutrient balancing in the context of evolution and cancer metabolism


While philosophers of science have marginally discussed concepts such as ‘nutrient’, ‘naturalness’, ‘food’, or the ‘molecularization’ of nutrition, they have yet to seriously engage with the nutrition sciences. In this paper, I offer one way to begin this engagement by investigating conceptual challenges facing the burgeoning field of nutritional ecology and the question of how organisms construct a ‘balanced’ diet. To provide clarity, I propose the distinction between nutrient balance as a property of foods or dietary patterns and nutrient balancing as an evolved capacity to regulate nutrient intake. This distinction raises conceptual and empirical issues, such as what properties constitute this capacity and whether they are the same in all organisms. Additionally, while scientists use the term ‘balancing’, its intension and extension need further clarification. Based on the literature, the properties of external nutrient detection, internal sensing of nutrient levels, and organismal regulation could provide a basic recipe for nutrient balancing. Next, using an evolutionary lens, I examine nutrient acquisition in some prokaryotes, slime molds, simple multicellular eukaryotes, and in the quirks of multicellular metabolism to raise questions about the origins and universality of balancing. Finally, I build on this explication of balance and balancing by considering how obesity and cancer might respectively elucidate problems of organismal nutrient imbalances versus disrupted cellular nutrient balancing.

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  1. Descriptions of a ‘healthy diet’ in nutrition textbooks present ‘variety’, ‘moderation’, ‘calorie control’, and ‘adequacy’ as aspects distinct from ‘balance’ (Sizer and Whitney 2020). Yet, each of the former can be reduced to balance, and a ‘healthy diet’ is quite often simply equated with a ‘balanced diet’ (see throughout (Ross et al. 2014)). Hence, balance, even if often vaguely defined or undefined, is arguably the central organizing concept.

  2. While some degree of conceptual ‘imprecision’ could facilitate the integration of research agendas (Neto 2020), it is nevertheless still clear that precision has benefits – e.g., avoiding ambiguity and/or producing fruitful generalizations. This is generally what the tradition of philosophical explication has in mind (Carnap 1963; Brun 2016) and I broadly see my project as an example of this.

  3. Some qualitative research investigating concepts in healthcare settings similarly distinguishes between ‘balance’ as a state and ‘balancing’ as a process (Lipworth et al. 2011). However, this focuses on how these terms are used by patients and healthcare workers rather than how they are operationalized in a biological context.

  4. Tangential to this, some philosophers question whether ‘balance’ is a useful concept in the ecological sciences (for instance (Cooper 2001)). As we will see, ‘balance’ has a rather specific meaning in nutritional ecology.

  5. Their focus is primarily on macronutrient ratios (proteins, carbohydrates, and fats) since these appear to produce the strongest links to health outcomes, but in theory their model can include any nutrient component (such as micronutrients or minerals), whole foods or dietary patterns (Raubenheimer and Simpson 2016, 2019).

  6. In their work, these authors broadly operationalize ‘Darwinian’ or evolutionary fitness in terms of rates of growth/development and the probability of surviving to a reproductive stage, which are then combined into a general ‘performance index’ (Simpson and Raubenheimer 2012, p. 32).

  7. While it may seem that specialists need only focus on energy intake instead of dietary composition, various studies have shown this to be inaccurate. Even if what is balanced is distinct or less complex (e.g., prioritizing fat instead of protein), and even if specialists are more sensitive to excesses than generalists, specialists still seem to seek a target intake ratio of specific nutrients (Simpson and Raubenheimer 2012, pp. 124–130).

  8. Further support can be found in the old tradition of experimentally altering organisms, e.g., removing part of a rodent involved in nutrient regulation and observing whether/how food preferences change to redress this ablation (Richter and Eckert 1937; Abrams et al. 1949; Leshem et al. 1999).

  9. There are various reasons for why these researchers have chosen to focus on nutrient ratios instead of energy (or caloric) balance, which has been common in traditional ecological models, such as optimal foraging theory. One reason is that while overall energy intake may be a limiting factor for what is consumed in some cases, this fails to explain why organisms (whether specialists or generalists) overeat some foods/nutrients rather than others, such as when making trade-offs in suboptimal food environments or when they are inefficient in digesting or utilizing certain nutrients (Raubenheimer et al. 2009). Focusing only on calories thus risks confounding maximizing specific macronutrients with maximizing energy.

  10. I thank an anonymous reviewer for highlighting this issue.

  11. Similarly: “We are confident that millions of years of natural selection have equipped animals with a physiology that is well qualified to estimate their own nutrient requirements” (Simpson and Raubenheimer 2012, p. 19). And: “How the animal allocates these nutrients is critical to fitness, and as a result natural selection has fashioned animal physiology to achieve a favorable strategy for investing its nutritional ‘income’ across its various requirements” (2012, p. 20).

  12. While it is possible that phagocytosis-like mechanisms were already present in some bacteria (Shiratori et al. 2019), it is nevertheless generally seen as a key eukaryotic feature.

  13. There is some evidence suggesting that AMPK preceded TOR in evolution, with the latter being a eukaryotic invention (Roustan et al. 2016).

  14. Like bacteria, T. adhaerens exhibits both individual and collective feeding (Fortunato and Aktipis 2019).

  15. While early forms of insulin pathways appear to exist already in some unicellular eukaryotes (Le Roith et al. 1980; Baig and Khaleeq 2020), their main function seems to be for regulating internal glucose homeostasis.

  16. I set aside debates over how to define obesity and instead focus on broader issues explaining why it occurs.

  17. For a philosophical analysis of ‘mismatch’ and its use in nutritional ecology, see (Bourrat and Griffiths 2021 forthcoming).

  18. In this case, an individual could eat a ‘balanced’ (fitness-optimizing) diet and still develop obesity or metabolic disorders. This would dissociate, to some degree, fitness and health outcomes. However, the link to fitness can be maintained if we distinguish costs to realized vs. expected fitness (Matthewson and Griffiths 2017, p. 456).


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I would like to warmly thank Maël Lemoine and Thomas Pradeu for their many generous comments and suggestions throughout the writing of the paper. I also kindly thank Paul Griffiths, Bertrand Daignan-Fornier, James DiFrisco, Pierrick Bourrat, and the entire ImmunoConcept team for their comments. My research was funded by Université de Bordeaux, Région Nouvelle-Aquitaine, and SIRIC-BRIO (Site de recherche intégrée sur le cancer – Bordeaux recherche intégrée oncologie). It was also made possible by the support of the PHIBIOMED program (Région Nouvelle-Aquitaine), grant #AAPR2020-2019-8209910.


Université de Bordeaux, Région Nouvelle-Aquitaine, and SIRIC-BRIO.

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Correspondence to Jonathan Sholl.

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Sholl, J. Everything in moderation or moderating everything? Nutrient balancing in the context of evolution and cancer metabolism. Biol Philos 37, 14 (2022).

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  • Nutrient balance
  • Nutrient balancing
  • Nutritional ecology
  • Evolution
  • Multicellularity
  • Cancer metabolism