Abstract
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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data Availability
Not applicable.
Code availability
Not applicable.
Notes
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.
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.
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.
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.
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).
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).
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).
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.
I thank an anonymous reviewer for highlighting this issue.
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).
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.
There is some evidence suggesting that AMPK preceded TOR in evolution, with the latter being a eukaryotic invention (Roustan et al. 2016).
Like bacteria, T. adhaerens exhibits both individual and collective feeding (Fortunato and Aktipis 2019).
I set aside debates over how to define obesity and instead focus on broader issues explaining why it occurs.
For a philosophical analysis of ‘mismatch’ and its use in nutritional ecology, see (Bourrat and Griffiths 2021 forthcoming).
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).
References
Abrams M, DeFriez AIC, Tosteson DC, Landis EM (1949) Self-selection of salt solutions and water by normal and hypertensive rats. Am J Physiol-Leg Content 156:233–247. https://doi.org/10.1152/ajplegacy.1949.156.2.233
Adiciptaningrum A, Osella M, Moolman MC et al (2016) Stochasticity and homeostasis in the E. coli replication and division cycle. Sci Rep 5:18261. https://doi.org/10.1038/srep18261
Altea‐Manzano P, Cuadros AM, Broadfield LA, Fendt S (2020) Nutrient metabolism and cancer in the in vivo context: a metabolic game of give and take. EMBO Rep 21. https://doi.org/10.15252/embr.202050635
Al-Zhoughbi W, Huang J, Paramasivan GS et al (2014) Tumor Macroenvironment and Metabolism. Semin Oncol 41:281–295. https://doi.org/10.1053/j.seminoncol.2014.02.005
Amend SR, Gatenby RA, Pienta KJ, Brown JS (2018) Cancer Foraging Ecology: Diet Choice, Patch Use, and Habitat Selection of Cancer Cells. Curr Pathobiol Rep 6:209–218. https://doi.org/10.1007/s40139-018-0185-7
Amtmann A, Blatt MR (2009) Regulation of macronutrient transport. New Phytol 181:35–52. https://doi.org/10.1111/j.1469-8137.2008.02666.x
Argilés JM, Busquets S, Stemmler B, López-Soriano FJ (2014) Cancer cachexia: understanding the molecular basis. Nat Rev Cancer 14:754–762. https://doi.org/10.1038/nrc3829
Baig AM, Khaleeq A (2020) First Reports of Effects of Insulin, Human-like Insulin Receptors and Adapter Proteins in Acanthamoeba castellanii. Sci Rep 10:11759. https://doi.org/10.1038/s41598-020-63435-4
Behmer ST, Raubenheimer D, Simpson SJ (2001) Frequency-dependent food selection in locusts: a geometric analysis of the role of nutrient balancing. Anim Behav 61:995–1005. https://doi.org/10.1006/anbe.2000.1695
Berardi E, Madaro L, Lozanoska-Ochser B et al (2021) A Pound of Flesh: What Cachexia Is and What It Is Not. Diagnostics 11:116. https://doi.org/10.3390/diagnostics11010116
Bertolaso M (2016) Philosophy of cancer: a dynamic and relational view. Springer, Berlin Heidelberg, New York
Bich L, Pradeu T, Moreau J-F (2019) Understanding Multicellularity: The Functional Organization of the Intercellular Space. Front Physiol 10:1170. https://doi.org/10.3389/fphys.2019.01170
Blackadar CB (2016) Historical review of the causes of cancer. WJCO 7:54. https://doi.org/10.5306/wjco.v7.i1.54
Bognon-Küss C (2019) Between biology and chemistry in the Enlightenment: how nutrition shapes vital organization. Buffon, Bonnet, C.F. Wolff. HPLS 41:11. https://doi.org/10.1007/s40656-019-0248-z
Bolduc J-S, Cézilly F (2012) Optimality modelling in the real world. Biol Philos 27:851–869. https://doi.org/10.1007/s10539-012-9333-3
Bonner JT (2010) Brainless behavior: A myxomycete chooses a balanced diet. Proc Natl Acad Sci 107:5267–5268. https://doi.org/10.1073/pnas.1000861107
Borer KT (2021) Why We Eat Too Much, Have an Easier Time Gaining Than Losing Weight, and Expend Too Little Energy: Suggestions for Counteracting or Mitigating These Problems. Nutrients 13:3812. https://doi.org/10.3390/nu13113812
Borghini A, Engisch P (eds) (2022) A philosophy of recipes: making, experiencing, and valuing, 1st edn. Bloomsbury Academic, New York
Borghini A, Piras N (2021) On Interpreting Something as Food. Food Ethics 6:1. https://doi.org/10.1007/s41055-020-00082-5
Borghini A, Piras N, Serini B (2021) Defective food concepts. Synthese 199:12225–12249. https://doi.org/10.1007/s11229-021-03330-1
Bourrat P, Griffiths P (forthcoming) The idea of mismatch in evolutionary medicine [preprint]. Philos Sci. http://philsci-archive.pitt.edu/19349/
Broach JR (2012) Nutritional Control of Growth and Development in Yeast. Genetics 192:73–105. https://doi.org/10.1534/genetics.111.135731
Brun G (2016) Explication as a Method of Conceptual Re-engineering. Erkenn 81:1211–1241. https://doi.org/10.1007/s10670-015-9791-5
Calle EE, Kaaks R (2004) Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 4:579–591. https://doi.org/10.1038/nrc1408
Camus MF, Fowler K, Piper MWD, Reuter M (2017) Sex and genotype effects on nutrient-dependent fitness landscapes in Drosophila melanogaster. Proc R Soc B 284:20172237. https://doi.org/10.1098/rspb.2017.2237
Cantor JR, Sabatini DM (2012) Cancer Cell Metabolism: One Hallmark, Many Faces. Cancer Discov 2:881–898. https://doi.org/10.1158/2159-8290.CD-12-0345
Cardenas D (2016) What is clinical nutrition? Understanding the epistemological foundations of a new discipline. Clinical Nutrition ESPEN 11:e63–e66. https://doi.org/10.1016/j.clnesp.2015.10.001
Carnap R (1963) Logical Foundations of Probability, 2nd edn. University Press, Chicago
Cavalier-Smith T (2002) The phagotrophic origin of eukaryotes and phylogenetic classification of Protozoa. Int J Syst Evol Microbiol 52:297–354. https://doi.org/10.1099/00207713-52-2-297
Cena H, Calder PC (2020) Defining a healthy diet: evidence for the role of contemporary dietary patterns in health and disease. Nutrients 12:334. https://doi.org/10.3390/nu12020334
Chadwick R (2000) Novel, natural, nutritious: towards a philosophy of food. P Aristotelian Soc 100:193–208. https://doi.org/10.1111/j.0066-7372.2003.00010.x
Chantranupong L, Wolfson RL, Sabatini DM (2015) Nutrient-Sensing Mechanisms across Evolution. Cell 161:67–83. https://doi.org/10.1016/j.cell.2015.02.041
Chen ST, Luo X, Hou R et al (2018) Nutrient Balancing by Captive Golden Snub-Nosed Monkeys (Rhinopithecus roxellana). Int J Primatol 39:1124–1138. https://doi.org/10.1007/s10764-018-0070-6
Chignell A, Cuneo T, Halteman MC (eds) (2016) Philosophy comes to dinner: arguments on the ethics of eating. Routledge-Taylor & Francis, New York
Cohen RW (2001) Diet Balancing in the Cockroach Rhyparobia madera: Does Serotonin Regulate this Behavior? J Insect Behav 14:99–111. https://doi.org/10.1023/A:1007805814388
Coller HA (2014) Is Cancer a Metabolic Disease? Am J Pathol 184:4–17. https://doi.org/10.1016/j.ajpath.2013.07.035
Cooper G (2001) Must There Be a Balance of Nature? Biol Philos 16:481–506. https://doi.org/10.1023/A:1011935220219
Cui X (2012) Nutrient Sensing in Plants. Mol Plant 5:1167–1169. https://doi.org/10.1093/mp/sss107
Curtin DW, Heldke LM (eds) (1992) Cooking, eating, thinking: transformative philosophies of food. Indiana University Press, Bloomington
Daignan-Fornier B, Laporte D, Sagot I (2021) Quiescence Through the Prism of Evolution. Front Cell Dev Biol 9:745069. https://doi.org/10.3389/fcell.2021.745069
Davis CM (1934) Studies in the Self-Selection of Diet by Young Children. J Am Dent Assoc (1992) 21:636–640. https://doi.org/10.14219/jada.archive.1934.0098
DeBerardinis RJ, Chandel NS (2016) Fundamentals of Cancer Metabolism. Sci Adv 2:e1600200. https://doi.org/10.1126/sciadv.1600200
Devic S (2016) Warburg Effect - a Consequence or the Cause of Carcinogenesis? J Cancer 7:817–822. https://doi.org/10.7150/jca.14274
Dussutour A, Latty T, Beekman M, Simpson SJ (2010) Amoeboid organism solves complex nutritional challenges. Proc Natl Acad Sci USA 107:4607. https://doi.org/10.1073/pnas.0912198107
Efeyan A, Comb WC, Sabatini DM (2015) Nutrient-sensing mechanisms and pathways. Nature 517:302–310. https://doi.org/10.1038/nature14190
Elia I, Doglioni G, Fendt S-M (2018) Metabolic Hallmarks of Metastasis Formation. Trends Cell Biol 28:673–684. https://doi.org/10.1016/j.tcb.2018.04.002
Engelberg-Kulka H, Amitai S, Kolodkin-Gal I, Hazan R (2006) Bacterial Programmed Cell Death and Multicellular Behavior in Bacteria. PLoS Genet 2:e135. https://doi.org/10.1371/journal.pgen.0020135
Faubert B, Solmonson A, DeBerardinis RJ (2020) Metabolic reprogramming and cancer progression. Science 368:eaaw5473. https://doi.org/10.1126/science.aaw5473
Ferenci T (2007) Sensing nutrient levels in bacteria. Nat Chem Biol 3:607–608. https://doi.org/10.1038/nchembio1007-607
Folker AP, Andersen H, Sandøe P (2008) Implicit Normativity in Scientific Advice: values in nutrition scientists’ decisions to give public advice. Perspect Biol Med 51:199–206. https://doi.org/10.1353/pbm.0.0001
Folker AP, Sandøe P (2008) Leaping “Out of the Doubt”—Nutrition Advice: Values at Stake in Communicating Scientific Uncertainty to the Public. Health Care Anal 16:176–191. https://doi.org/10.1007/s10728-007-0054-8
Font-Burgada J, Sun B, Karin M (2016) Obesity and Cancer: The Oil that Feeds the Flame. Cell Metab 23:48–62. https://doi.org/10.1016/j.cmet.2015.12.015
Fortunato A, Aktipis A (2019) Social Feeding Behavior of Trichoplax adhaerens. Front Ecol Evol 7:19. https://doi.org/10.3389/fevo.2019.00019
Galef BG (1996) Food selection: Problems in understanding how we choose foods to eat. Neurosci Biobehav Rev 20:67–73. https://doi.org/10.1016/0149-7634(95)00041-C
Galef BG (1991) A contrarian view of the wisdom of the body as it relates to dietary self-selection. Psychol Rev 98:218–223. https://doi.org/10.1037/0033-295X.98.2.218
Galef BG (1981) Development of flavor preference in man and animals: the role of social and nonsocial factors. In: Aslin RN, Alberts JR, Peterson MR (eds) Development of perception: psychobiological perspectives. Academic Press, New York, pp 411–431
Gillies RJ, Robey I, Gatenby RA (2008) Causes and Consequences of Increased Glucose Metabolism of Cancers. J Nucl Med 49:24S-42S. https://doi.org/10.2967/jnumed.107.047258
Giroux É (ed) (2016) Naturalism in the Philosophy of Health: Issues and Implications, 1st ed. 2016. Springer International Publishing : Imprint: Springer, Cham
González A, Hall MN, Lin S-C, Hardie DG (2020) AMPK and TOR: The Yin and Yang of Cellular Nutrient Sensing and Growth Control. Cell Metab 31:472–492. https://doi.org/10.1016/j.cmet.2020.01.015
Gosby AK, Conigrave AD, Raubenheimer D, Simpson SJ (2014) Protein leverage and energy intake. Obes Rev 15:183–191. https://doi.org/10.1111/obr.12131
Gould SJ (1996) Full House: The Spread of Excellence from Plato to Darwin. Three Rivers Press, New York
Hall KD (2020) Challenges of human nutrition research. Science 367:1298–1300. https://doi.org/10.1126/science.aba3807
Hall KD, Farooqi IS, Friedman JM, et al (2022) The energy balance model of obesity: beyond calories in, calories out. Am J Clin Nutr nqac031. https://doi.org/10.1093/ajcn/nqac031
Hall KD, Guo J (2017) Obesity Energetics: Body Weight Regulation and the Effects of Diet Composition. Gastroenterology 152:1718-1727.e3. https://doi.org/10.1053/j.gastro.2017.01.052
Hall KD, Heymsfield SB, Kemnitz JW et al (2012) Energy balance and its components: implications for body weight regulation. Am J Clin Nutr 95:989–994. https://doi.org/10.3945/ajcn.112.036350
Hanahan D, Weinberg RA (2011) Hallmarks of Cancer: The Next Generation. Cell 144:646–674. https://doi.org/10.1016/j.cell.2011.02.013
Haq R (2014) Metabolic Dysregulation in Melanoma: Cause or Consequence? Cancer Discov 4:390–391. https://doi.org/10.1158/2159-8290.CD-14-0173
Hoffmann I (2003) Transcending reductionism in nutrition research. Am J Clin Nutr 78:514S-516S. https://doi.org/10.1093/ajcn/78.3.514S
Ioannidis JPA (2013) Implausible results in human nutrition research. BMJ 347:f6698–f6698. https://doi.org/10.1136/bmj.f6698
Ioannidis JPA (2018) The Challenge of Reforming Nutritional Epidemiologic Research. JAMA 320:969. https://doi.org/10.1001/jama.2018.11025
Jacobs DR, Tapsell LC (2008) Food, Not Nutrients, Is the Fundamental Unit in Nutrition. Nutr Rev 65:439–450. https://doi.org/10.1111/j.1753-4887.2007.tb00269.x
Johnson CA, Raubenheimer D, Rothman JM et al (2013) 30 Days in the Life: Daily Nutrient Balancing in a Wild Chacma Baboon. PLoS ONE 8:e70383. https://doi.org/10.1371/journal.pone.0070383
Jukola S (2019a) On the evidentiary standards for nutrition advice. Stud Hist Philos Sci C 73:1–9. https://doi.org/10.1016/j.shpsc.2018.05.007
Jukola S (2019b) Commercial interests, agenda setting, and the epistemic trustworthiness of nutrition science. Synthese. https://doi.org/10.1007/s11229-019-02228-3
Kaplan DM (ed) (2012) The Philosophy of Food. University of California Press, Berkeley
Katz DL, Meller S (2014) Can We Say What Diet Is Best for Health? Annu Rev Public Health 35:83–103. https://doi.org/10.1146/annurev-publhealth-032013-182351
Kingma E (2014) Naturalism about Health and Disease: Adding Nuance for Progress. J Med Philos 39:590–608
Klimentidis YC, Beasley TM, Lin H-Y et al (2011) Canaries in the coal mine: a cross-species analysis of the plurality of obesity epidemics. Proc R Soc B 278:1626–1632. https://doi.org/10.1098/rspb.2010.1890
Korsmeyer C (2002) Making sense of taste: food and philosophy, 1st pr. Cornell paperb. Cornell Univ. Press, Ithaca
Kroemer G, Pouyssegur J (2008) Tumor Cell Metabolism: Cancer’s Achilles’ Heel. Cancer Cell 13:472–482. https://doi.org/10.1016/j.ccr.2008.05.005
Kwon G, Marshall CA, Pappan KL et al (2004) Signaling Elements Involved in the Metabolic Regulation of mTOR by Nutrients, Incretins, and Growth Factors in Islets. Diabetes 53:S225–S232. https://doi.org/10.2337/diabetes.53.suppl_3.S225
Le Roith D, Shiloach J, Roth J, Lesniak MA (1980) Evolutionary origins of vertebrate hormones: substances similar to mammalian insulins are native to unicellular eukaryotes. Proc Natl Acad Sci 77:6184–6188. https://doi.org/10.1073/pnas.77.10.6184
Lee KP, Kwon S-T, Roh C (2012) Caterpillars use developmental plasticity and diet choice to overcome the early life experience of nutritional imbalance. Anim Behav 84:785–793. https://doi.org/10.1016/j.anbehav.2012.06.033
Lee KP, Simpson SJ, Clissold FJ et al (2008) Lifespan and reproduction in Drosophila: New insights from nutritional geometry. Proc Natl Acad Sci 105:2498–2503. https://doi.org/10.1073/pnas.0710787105
Leshem M, Del Canho S, Schulkin J (1999) Calcium Hunger in the Parathyroidectomized Rat Is Specific. Physiol Behav 67:555–559. https://doi.org/10.1016/S0031-9384(99)00113-4
Levine ME, Suarez JA, Brandhorst S et al (2014) Low Protein Intake Is Associated with a Major Reduction in IGF-1, Cancer, and Overall Mortality in the 65 and Younger but Not Older Population. Cell Metab 19:407–417. https://doi.org/10.1016/j.cmet.2014.02.006
Lewens T (2009) Seven Types of Adaptationism. Biol Philos 24:161–182
Liesenfeld DB, Habermann N, Owen RW et al (2013) Review of Mass Spectrometry-Based Metabolomics in Cancer Research. Cancer Epidemiol Biomarkers Prev 22:2182–2201. https://doi.org/10.1158/1055-9965.EPI-13-0584
Lihoreau M, Buhl J, Charleston MA et al (2014) Modelling nutrition across organizational levels: From individuals to superorganisms. J Insect Physiol 69:2–11. https://doi.org/10.1016/j.jinsphys.2014.03.004
Lineweaver CH, Bussey KJ, Blackburn AC, Davies PCW (2021) Cancer progression as a sequence of atavistic reversions. BioEssays 2000305. https://doi.org/10.1002/bies.202000305
Lipworth WL, Hooker C, Carter SM (2011) Balance, Balancing, and Health. Qual Health Res 21:714–725. https://doi.org/10.1177/1049732311399781
Ludwig DS, Aronne LJ, Astrup A, et al (2021) The carbohydrate-insulin model: a physiological perspective on the obesity pandemic. Am J Clin Nutr nqab270. https://doi.org/10.1093/ajcn/nqab270
Ludwig DS, Kushi LH, Heymsfield SB (2018) Conflicts of Interest in Nutrition Research. JAMA 320:93. https://doi.org/10.1001/jama.2018.5658
Lunt SY, Fendt S-M (2018) Metabolism – A cornerstone of cancer initiation, progression, immune evasion and treatment response. Curr Opin Syst Biol 8:67–72. https://doi.org/10.1016/j.coisb.2017.12.006
Maklakov AA, Simpson SJ, Zajitschek F et al (2008) Sex-Specific Fitness Effects of Nutrient Intake on Reproduction and Lifespan. Curr Biol 18:1062–1066. https://doi.org/10.1016/j.cub.2008.06.059
Margulis L (1975) Symbiotic theory of the origin of eukaryotic organelles; criteria for proof. Symp Soc Exp Biol 29:21–38. PMID: 822529.
Marshall S (2006) Role of Insulin, Adipocyte Hormones, and Nutrient-Sensing Pathways in Regulating Fuel Metabolism and Energy Homeostasis: A Nutritional Perspective of Diabetes, Obesity, and Cancer. Sci STKE 2006(346):re7. https://doi.org/10.1126/stke.3462006re7
Matthewson J, Griffiths PE (2017) Biological criteria of disease: four ways of going wrong. J Med Philos 42:447–466. https://doi.org/10.1093/jmp/jhx004
Mayntz D, Nielsen VH, Sørensen A et al (2009) Balancing of protein and lipid intake by a mammalian carnivore, the mink, Mustela vison. Anim Behav 77:349–355. https://doi.org/10.1016/j.anbehav.2008.09.036
Mente A, Yusuf S (2018) Evolving evidence about diet and health. Lancet Pub Health 3:e408–e409. https://doi.org/10.1016/S2468-2667(18)30160-9
Méthot P-O (2011) Research Traditions and Evolutionary Explanations in Medicine. Theor Med Bioeth 32:75–90
Minderis P, Fokin A, Dirmontas M et al (2021) Caloric Restriction per se Rather Than Dietary Macronutrient Distribution Plays a Primary Role in Metabolic Health and Body Composition Improvements in Obese Mice. Nutrients 13:3004. https://doi.org/10.3390/nu13093004
Mony VK, Benjamin S, O’Rourke EJ (2016) A lysosome-centered view of nutrient homeostasis. Autophagy 12:619–631. https://doi.org/10.1080/15548627.2016.1147671
Moore LL, Chadid S, Singer MR et al (2014) Metabolic Health Reduces Risk of Obesity-Related Cancer in Framingham Study Adults. Cancer Epidemiol Biomarkers Prev 23:2057–2065. https://doi.org/10.1158/1055-9965.EPI-14-0240
Mozaffarian D, Forouhi NG (2018) Dietary guidelines and health—is nutrition science up to the task? BMJ k822. https://doi.org/10.1136/bmj.k822
Muscaritoli M, Anker SD, Argilés J et al (2010) Consensus definition of sarcopenia, cachexia and pre-cachexia: Joint document elaborated by Special Interest Groups (SIG) “cachexia-anorexia in chronic wasting diseases” and “nutrition in geriatrics.” Clin Nutr 29:154–159. https://doi.org/10.1016/j.clnu.2009.12.004
Nedelcu AM (2020) The evolution of multicellularity and cancer: views and paradigms. Biochem Soc Trans 48:1505–1518. https://doi.org/10.1042/BST20190992
Nestle M (2007) Food politics: how the food industry influences nutrition and health, Rev. and expanded ed. University of California Press, Berkeley
Neto C (2020) When imprecision is a good thing, or how imprecise concepts facilitate integration in biology. Biol Philos 35:58. https://doi.org/10.1007/s10539-020-09774-y
Neumann N, Doello S, Forchhammer K (2021) Recovery of Unicellular Cyanobacteria from Nitrogen Chlorosis: A Model for Resuscitation of Dormant Bacteria. Microb Physiol 31:78–87. https://doi.org/10.1159/000515742
Oettmeier C, Döbereiner H-G (2019) Mitochondrial numbers increase during glucose deprivation in the slime mold Physarum polycephalum. Protoplasma 256:1647–1655. https://doi.org/10.1007/s00709-019-01410-1
Okasha S (forthcoming) Cancer and the Levels of Selection [preprint]. Brit J Philos Sci. http://philsci-archive.pitt.edu/19192/
O’Malley MA (2010) The first eukaryote cell: an unfinished history of contestation. Stud Hist Philos Sci C 41:212–224. https://doi.org/10.1016/j.shpsc.2010.07.010
O’Malley MA, Dupré J (2007) Size doesn’t matter: towards a more inclusive philosophy of biology. Biol Philos 22:155–191. https://doi.org/10.1007/s10539-006-9031-0
Orland B, Spary EC (2012) Introduction. Stud Hist Philos Sci C 43:317–322. https://doi.org/10.1016/j.shpsc.2011.10.023
Orzack SH, Sober E (eds) (2001) Adaptationism and Optimality (Cambridge Studies in Philosophy and Biology) Cambridge University Press, Cambridge. https://doi.org/10.1017/CBO9780511609084
Palm W, Thompson CB (2017) Nutrient acquisition strategies of mammalian cells. Nature 546:234–242. https://doi.org/10.1038/nature22379
Patel S, Ahmed S (2015) Emerging field of metabolomics: Big promise for cancer biomarker identification and drug discovery. J Pharm Biomed Anal 107:63–74. https://doi.org/10.1016/j.jpba.2014.12.020
Pavlova NN, Thompson CB (2016) The Emerging Hallmarks of Cancer Metabolism. Cell Metab 23:27–47. https://doi.org/10.1016/j.cmet.2015.12.006
Persson J, Fink P, Goto A et al (2010) To be or not to be what you eat: regulation of stoichiometric homeostasis among autotrophs and heterotrophs. Oikos 119:741–751. https://doi.org/10.1111/j.1600-0706.2009.18545.x
Pfeiffer T, Bonhoeffer S (2003) An evolutionary scenario for the transition to undifferentiated multicellularity. Proc Natl Acad Sci 100:1095–1098. https://doi.org/10.1073/pnas.0335420100
Plutynski A (2018) The Origins of “Dynamic Reciprocity”: Mina Bissell’s Expansive Picture of Cancer Causation. In: Harman O, Dietrich MR (eds) Dreamers, Visionaries, and Revolutionaries in the Life Sciences. University of Chicago Press, pp 96–110
Potochnik A (2009) Optimality modeling in a suboptimal world. Biol Philos 24:183–197. https://doi.org/10.1007/s10539-008-9143-9
Provenza FD, Balph DF (1990) Applicability of Five Diet-Selection Models to Various Foraging Challenges Ruminants Encounter. In: Hughes RN (ed) Behavioural Mechanisms of Food Selection. Springer, Berlin Heidelberg, Berlin, Heidelberg, pp 423–460
Raubenheimer D, Jones SA (2006) Nutritional imbalance in an extreme generalist omnivore: tolerance and recovery through complementary food selection. Anim Behav 71:1253–1262. https://doi.org/10.1016/j.anbehav.2005.07.024
Raubenheimer D, Machovsky-Capuska GE, Gosby AK, Simpson S (2015) Nutritional ecology of obesity: from humans to companion animals. Br J Nutr 113:S26–S39. https://doi.org/10.1017/S0007114514002323
Raubenheimer D, Simpson SJ (1997) Integrative models of nutrient balancing: application to insects and vertebrates. Nutr Res Rev 10:151–179. https://doi.org/10.1079/NRR19970009
Raubenheimer D, Simpson SJ (2020) Eat Like the Animals: What Nature Teaches Us About the Science of Healthy Eating. Houghton Mifflin Harcourt, Boston
Raubenheimer D, Simpson SJ (2019) Protein Leverage: Theoretical Foundations and Ten Points of Clarification. Obesity 27:1225–1238. https://doi.org/10.1002/oby.22531
Raubenheimer D, Simpson SJ (2016) Nutritional Ecology and Human Health. Annu Rev Nutr 36:603–626. https://doi.org/10.1146/annurev-nutr-071715-051118
Raubenheimer D, Simpson SJ, Mayntz D (2009) Nutrition, ecology and nutritional ecology: toward an integrated framework. Funct Ecol 23:4–16. https://doi.org/10.1111/j.1365-2435.2009.01522.x
Raubenheimer D, Simpson SJ, Tait AH (2012) Match and mismatch: conservation physiology, nutritional ecology and the timescales of biological adaptation. Phil Trans R Soc B 367:1628–1646. https://doi.org/10.1098/rstb.2012.0007
Richter CP, Eckert JF (1937) Increased calcium appetite of parathyroidectomized rats. Endocrinology 21:50–54. https://doi.org/10.1210/endo-21-1-50
Richter CP, Holt LE, Barelare B (1938) Nutritional requirements for normal growth and reproduction in rats studied by the self-selection method. Am J Physiol-Leg Content 122:734–744. https://doi.org/10.1152/ajplegacy.1938.122.3.734
Ringel AE, Drijvers JM, Baker GJ et al (2020) Obesity Shapes Metabolism in the Tumor Microenvironment to Suppress Anti-Tumor Immunity. Cell 183:1848-1866.e26. https://doi.org/10.1016/j.cell.2020.11.009
Roberts MT, Bermingham EN, Cave NJ et al (2018) Macronutrient intake of dogs, self-selecting diets varying in composition offered ad libitum. J Anim Physiol Anim Nutr 102:568–575. https://doi.org/10.1111/jpn.12794
Ross AC, Caballero B, Cousins R et al (eds) (2014) Modern nutrition in health and disease, 11th edn. Wolters Kluwer Health/Lippincott Williams & Wilkins, Philadelphia
Roustan V, Jain A, Teige M et al (2016) An evolutionary perspective of AMPK–TOR signaling in the three domains of life. EXBOTJ 67:3897–3907. https://doi.org/10.1093/jxb/erw211
Rozin P (1976) The Selection of Foods by Rats, Humans, and Other Animals. In: Advances in the Study of Behavior. Elsevier, pp 21–76
Sagan L (1967) On the origin of mitosing cells. J Theor Biol 14:225-IN6. https://doi.org/10.1016/0022-5193(67)90079-3
Saito S, Uozumi N (2020) Calcium-Regulated Phosphorylation Systems Controlling Uptake and Balance of Plant Nutrients. Front Plant Sci 11:44. https://doi.org/10.3389/fpls.2020.00044
Saldanha AJ, Brauer MJ, Botstein D (2004) Nutritional Homeostasis in Batch and Steady-State Culture of Yeast. MBoC 15:4089–4104. https://doi.org/10.1091/mbc.e04-04-0306
Sandler RL (2014) Food ethics: the basics. Routledge, Taylor & Francis Group, London ; New York
Satriano L, Lewinska M, Rodrigues PM et al (2019) Metabolic rearrangements in primary liver cancers: cause and consequences. Nat Rev Gastroenterol Hepatol 16:748–766. https://doi.org/10.1038/s41575-019-0217-8
Scrinis G (2013) Nutritionism: the science and politics of dietary advice. Columbia University Press, New York
Scruton R (2010) I drink therefore I am: a philosopher’s guide to wine, Pbk. ed. Continuum, London : New York
Sepp T, Ujvari B, Ewald PW et al (2019) Urban environment and cancer in wildlife: available evidence and future research avenues. Proc R Soc B 286:20182434. https://doi.org/10.1098/rspb.2018.2434
Séron K, Blondel M-O, Haguenauer-Tsapis R, Volland C (1999) Uracil-Induced Down-Regulation of the Yeast Uracil Permease. J Bacteriol 181:1793–1800. https://doi.org/10.1128/JB.181.6.1793-1800.1999
Shi H, Westfall CS, Kao J et al (2021) Starvation induces shrinkage of the bacterial cytoplasm. Proc Natl Acad Sci USA 118:e2104686118. https://doi.org/10.1073/pnas.2104686118
Shik JZ, Dussutour A (2020) Nutritional Dimensions of Invasive Success. Trends Ecol Evol 35:691–703. https://doi.org/10.1016/j.tree.2020.03.009
Shiratori T, Suzuki S, Kakizawa Y, Ishida K (2019) Phagocytosis-like cell engulfment by a planctomycete bacterium. Nat Commun 10:5529. https://doi.org/10.1038/s41467-019-13499-2
Siipi H (2013) Is Natural Food Healthy? J Agric Environ Ethics 26:797–812. https://doi.org/10.1007/s10806-012-9406-y
Simpson SJ, Le Couteur DG, Raubenheimer D (2015) Putting the Balance Back in Diet. Cell 161:18–23. https://doi.org/10.1016/j.cell.2015.02.033
Simpson SJ, Raubenheimer D (1993) A multi-level analysis of feeding behaviour: the geometry of nutritional decisions. Phil Trans R Soc Lond B 342:381–402. https://doi.org/10.1098/rstb.1993.0166
Simpson SJ, Raubenheimer D (2012) The Nature of Nutrition: A Unifying Framework from Animal Adaptation to Human Obesity. Princeton University Press, Princeton
Simpson SJ, Raubenheimer D (2005) Obesity: the protein leverage hypothesis. Obes Rev 6:133–142. https://doi.org/10.1111/j.1467-789X.2005.00178.x
Simpson SJ, Raubenheimer D (2009) Macronutrient balance and lifespan. Aging 1:875–880. https://doi.org/10.18632/aging.100098
Simpson SJ, Raubenheimer D, Behmer ST et al (2002) A comparison of nutritional regulation in solitarious- and gregarious-phase nymphs of the desert locust Schistocerca gregaria. J Exp Biol 205:121–129. https://doi.org/10.1242/jeb.205.1.121
Singer P (2009) Animal liberation: the definitive classic of the animal movement, Updated ed., 1st Ecco pbk. ed., 1st Harper Perennial ed. Ecco Book/Harper Perennial, New York
Sizer FS, Whitney EN (2020) Nutrition: Concepts & Controversies, Fifteenth. Cengage Learning, Boston
Smith BC (ed) (2007) Questions of taste: the philosophy of wine. Oxford Univ. Press, Oxford
Smith CL, Mayorova TD (2019) Insights into the evolution of digestive systems from studies of Trichoplax adhaerens. Cell Tissue Res 377:353–367. https://doi.org/10.1007/s00441-019-03057-z
Smith CL, Reese TS, Govezensky T, Barrio RA (2019) Coherent directed movement toward food modeled in Trichoplax, a ciliated animal lacking a nervous system. Proc Natl Acad Sci USA 116:8901–8908. https://doi.org/10.1073/pnas.1815655116
Sohal RS, Forster MJ (2014) Caloric restriction and the aging process: a critique. Free Radical Biol Med 73:366–382. https://doi.org/10.1016/j.freeradbiomed.2014.05.015
Solon-Biet SM, McMahon AC, Ballard JWO et al (2014) The Ratio of Macronutrients, Not Caloric Intake, Dictates Cardiometabolic Health, Aging, and Longevity in Ad Libitum-Fed Mice. Cell Metab 19:418–430. https://doi.org/10.1016/j.cmet.2014.02.009
Solon-Biet SM, Walters KA, Simanainen UK et al (2015) Macronutrient balance, reproductive function, and lifespan in aging mice. Proc Natl Acad Sci USA 112:3481–3486. https://doi.org/10.1073/pnas.1422041112
Sourjik V, Wingreen NS (2012) Responding to chemical gradients: bacterial chemotaxis. Curr Opin Cell Biol 24:262–268. https://doi.org/10.1016/j.ceb.2011.11.008
Srivastava M, Begovic E, Chapman J et al (2008) The Trichoplax genome and the nature of placozoans. Nature 454:955–960. https://doi.org/10.1038/nature07191
Stearns SC, Koella JC (eds) (2008) Evolution in Health and Disease, Second. Oxford University Press, Oxford
Stocker R (2012) Marine Microbes See a Sea of Gradients. Science 338:628–633. https://doi.org/10.1126/science.1208929
Strauss B, Bertolaso M, Ernberg I, Bissell MJ (eds) (2021) Rethinking cancer: a new paradigm for the postgenomics era. The MIT Press, Cambridge. https://doi.org/10.7551/mitpress/12111.001.0001
Ströhle A, Döring F (2010) Molecularization in nutritional science: A view from philosophy of science. Mol Nutr Food Res 54:1385–1404. https://doi.org/10.1002/mnfr.201000078
Swinburn BA, Sacks G, Lo SK et al (2009) Estimating the changes in energy flux that characterize the rise in obesity prevalence. Am J Clin Nutr 89:1723–1728. https://doi.org/10.3945/ajcn.2008.27061
Tang K-H, Tang YJ, Blankenship RE (2011) Carbon Metabolic Pathways in Phototrophic Bacteria and Their Broader Evolutionary Implications. Front Microbio 2. https://doi.org/10.3389/fmicb.2011.00165
Taubes G (2012) Unraveling the Obesity-Cancer Connection. Science 335:28–32. https://doi.org/10.1126/science.335.6064.28
Telfer E (1996) Food for thought: philosophy and food. Routledge, London, New York
Theodoratou E, Timofeeva M, Li X et al (2017) Nature, Nurture, and Cancer Risks: Genetic and Nutritional Contributions to Cancer. Annu Rev Nutr 37:293–320. https://doi.org/10.1146/annurev-nutr-071715-051004
Thompson PB (2015) From field to fork: food ethics for everyone. Oxford University Press, Oxford, New York
Titley MA, Snaddon JL, Turner EC (2017) Scientific research on animal biodiversity is systematically biased towards vertebrates and temperate regions. PLoS ONE 12:e0189577. https://doi.org/10.1371/journal.pone.0189577
Trigos AS, Pearson RB, Papenfuss AT, Goode DL (2017) Altered interactions between unicellular and multicellular genes drive hallmarks of transformation in a diverse range of solid tumors. Proc Natl Acad Sci USA 114:6406–6411. https://doi.org/10.1073/pnas.1617743114
Vandevijvere S, Chow CC, Hall KD et al (2015) Increased food energy supply as a major driver of the obesity epidemic: a global analysis. Bull World Health Organ 93:446–456. https://doi.org/10.2471/BLT.14.150565
Vineis P, Illari P, Russo F (2017) Causality in cancer research: a journey through models in molecular epidemiology and their philosophical interpretation. Emerg Themes Epidemiol 14:7. https://doi.org/10.1186/s12982-017-0061-7
Vivas M, Sánchez-Vázquez FJ, García García B, Madrid JA (2003) Macronutrient self-selection in European sea bass in response to dietary protein or fat restriction: Protein or fat restriction in macronutrient self-selection in sea bass. Aquac Res 34:271–280. https://doi.org/10.1046/j.1365-2109.2003.00799.x
Wahrheit J, Nicolae A, Heinzle E (2011) Eukaryotic metabolism: Measuring compartment fluxes. Biotechnol J 6:1071–1085. https://doi.org/10.1002/biot.201100032
Wang JD, Levin PA (2009) Metabolism, cell growth and the bacterial cell cycle. Nat Rev Microbiol 7:822–827. https://doi.org/10.1038/nrmicro2202
Ward PS, Thompson CB (2012) Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate. Cancer Cell 21:297–308. https://doi.org/10.1016/j.ccr.2012.02.014
West SA, Fisher RM, Gardner A, Kiers ET (2015) Major evolutionary transitions in individuality. Proc Natl Acad Sci USA 112:10112. https://doi.org/10.1073/pnas.1421402112
Willett WC (1994) Diet and Health: What Should We Eat? Science 264:532–537
Xiao Z, Dai Z, Locasale JW (2019) Metabolic landscape of the tumor microenvironment at single cell resolution. Nat Commun 10:3763. https://doi.org/10.1038/s41467-019-11738-0
Yasid NA, Rolfe MD, Green J, Williamson MP (2016) Homeostasis of metabolites in Escherichia coli on transition from anaerobic to aerobic conditions and the transient secretion of pyruvate. R Soc Open Sci 3:160187. https://doi.org/10.1098/rsos.160187
Zheng Z-L (2009) Carbon and nitrogen nutrient balance signaling in plants. Plant Signal Behav 4:584–591. https://doi.org/10.4161/psb.4.7.8540
Zitvogel L, Pietrocola F, Kroemer G (2017) Nutrition, inflammation and cancer. Nat Immunol 18:843–850. https://doi.org/10.1038/ni.3754
Acknowledgements
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.
Funding
Université de Bordeaux, Région Nouvelle-Aquitaine, and SIRIC-BRIO.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflicts of interest/Competing interests
None.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Sholl, J. Everything in moderation or moderating everything? Nutrient balancing in the context of evolution and cancer metabolism. Biol Philos 37, 14 (2022). https://doi.org/10.1007/s10539-022-09845-2
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s10539-022-09845-2