The Remaining Mysteries About Food

When scientists cracked the human genome in 2003 – sequencing the entire genetic code of a human being – many expected it would unlock the secrets of disease.¹⁾Fact Sheet – Human Genome Project But genetics explained only about 10% of the risk. The other 90% lies in the environment – and diet plays a huge part.²⁾Candela K. Genetics and Health: What Percentage of Diseases Are Genetic? Parsley Health

Worldwide, poor diet is linked to around one in five deaths among adults aged 25 years or older.³⁾Afshin, Ashkan et al. Health effects of dietary risks in 195 countries, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017 The Lancet, Volume 393, Issue 10184, 1958 – 1972 In Europe, it accounts for nearly half of all cardiovascular deaths.⁴⁾Meier T, Gräfe K, Senn F, Sur P, Stangl GI, Dawczynski C, März W, Kleber ME, Lorkowski S. Cardiovascular mortality attributable to dietary risk factors in 51 countries in the WHO European Region from 1990 to 2016: a systematic analysis of the Global Burden of Disease Study. Eur J Epidemiol. 2019 Jan;34(1):37-55. doi: 10.1007/s10654-018-0473-x

But despite decades of advice about cutting fat, salt or sugar, obesity and diet-related illness have continued to rise. Clearly, something is missing from the way we think about food.⁵⁾Benton D. Tackling the Obesity Crisis. Beyond Failed Approaches to Lasting Solutions. Springer 2024

For years, nutrition has often been framed in fairly simple terms: food as fuel and nutrients as the body’s building blocks. Proteins, carbohydrates, fats and vitamins – about 150 known chemicals in total – have dominated the picture. But scientists now estimate our diet actually delivers more than 26,000 compounds, with most of them still uncharted.⁶⁾Barabási, AL., Menichetti, G. & Loscalzo, J. The unmapped chemical complexity of our diet. Nat Food 1, 33–37 (2020). https://doi.org/10.1038/s43016-019-0005-1

Here is where astronomy provides a useful comparison. Astronomers know that dark matter makes up about 27% of the universe. It doesn’t emit or reflect light, and so it cannot be seen directly but its gravitational effects reveal that it must exist.⁷⁾Dark Matter. CERN

Nutrition science faces something similar. The vast majority of chemicals in food are invisible to us in terms of research. We consume them every day, but we have little idea what they do.

Some experts refer to these unknown molecules as “nutritional dark matter”. It’s a reminder that just as the cosmos is filled with hidden forces, our diet is packed with hidden chemistry.⁸⁾Bland JS. The Dark Matter of Nutrition: Dietary Signals Beyond Traditional Nutrients. Integr Med (Encinitas). 2019 Apr;18(2):12-15. PMID: 31341437; PMCID: PMC6601448.

When researchers analyze disease, they look at a vast array of foods, although any association often cannot be matched to known molecules. This is the dark matter of nutrition – the compounds we ingest daily but haven’t been mapped or studied. Some may encourage health, but others may increase the risk of disease. The challenge is finding out which do what.

Foodomics

The field of foodomics aims to do exactly that. It brings together genomics (the role of genes), proteomics (proteins), metabolomics (cell activity) and nutrigenomics (the interaction of genes and diet).

These approaches are starting to reveal how diet interacts with the body in ways far beyond calories and vitamins.

Take the Mediterranean diet (filled with fruits, vegetables, whole grains, legumes, nuts, olive oil and fish, with limited red meat and sweets), for example, which is known to reduce the risk of heart disease.⁹⁾Widmer RJ, Flammer AJ, Lerman LO, Lerman A. The Mediterranean diet, its components, and cardiovascular disease. Am J Med. 2015 Mar;128(3):229-38. doi: 10.1016/j.amjmed.2014.10.014. Epub 2014 Oct 15. doi: 10.1016/j.amjmed.2014.10.014

But why does it work? One clue lies in a molecule called TMAO (trimethylamine N-oxide), produced when gut bacteria metabolize compounds in red meat and eggs.¹⁰⁾Constantino-Jonapa LA, Espinoza-Palacios Y, Escalona-Montaño AR, Hernández-Ruiz P, Amezcua-Guerra LM, Amedei A, Aguirre-García MM. Contribution of Trimethylamine N-Oxide (TMAO) to Chronic Inflammatory and Degenerative Diseases. Biomedicines. 2023 Feb 2;11(2):431. doi: 10.3390/biomedicines11020431. High levels of TMAO increase the risk of heart disease. But garlic, for example, contains substances that block its production. This is one example of how diet can tip the balance between health and harm.¹¹⁾Panyod S, Wu WK, Chen PC, Chong KV, Yang YT, Chuang HL, Chen CC, Chen RA, Liu PY, Chung CH, Huang HS, Lin AY, Shen TD, Yang KC, Huang TF, Hsu CC, Ho CT, Kao HL, Orekhov AN, Wu MS, Sheen LY. Atherosclerosis amelioration by allicin in raw garlic through gut microbiota and trimethylamine-N-oxide modulation. NPJ Biofilms Microbiomes. 2022 Jan 27;8(1):4. DOI: 10.1038/s41522-022-00266-3

Gut bacteria also play a major role. When compounds reach the colon, microbes transform them into new chemicals that can affect inflammation, immunity and metabolism.¹²⁾Rowland I, Gibson G, Heinken A, Scott K, Swann J, Thiele I, Tuohy K. Gut microbiota functions: metabolism of nutrients and other food components. Eur J Nutr. 2018 Feb;57(1):1-24. DOI: 10.1007/s00394-017-1445-8

For example, ellagic acid – found in various fruits and nuts – is converted by gut bacteria into urolithins. These are a group of natural compounds that help keep our mitochondria (the body’s energy factories) healthy.¹³⁾García-Villalba R, Giménez-Bastida JA, Cortés-Martín A, Ávila-Gálvez MÁ, Tomás-Barberán FA, Selma MV, Espín JC, González-Sarrías A. Urolithins: a Comprehensive Update on their Metabolism, Bioactivity, and Associated Gut Microbiota. Mol Nutr Food Res. 2022 Nov;66(21):e2101019. DOI: 10.1002/mnfr.202101019

This shows how food is a complex web of interacting chemicals. One compound can influence many biological mechanisms, which in turn can affect many others. Diet can even switch genes on or off through epigenetics – changes in gene activity that don’t alter DNA itself.

History has provided stark examples of this. For example, children born to mothers who endured famine in the Netherlands during the second world war were more likely to develop heart disease, type 2 diabetes and schizophrenia later in life. Decades on, scientists found their gene activity had been altered by what their mothers ate – or didn’t eat – while pregnant.¹⁴⁾Tobi EW, Slieker RC, Luijk R, Dekkers KF, Stein AD, Xu KM; Biobank-based Integrative Omics Studies Consortium; Slagboom PE, van Zwet EW, Lumey LH, Heijmans BT. DNA methylation as a mediator of the association between prenatal adversity and risk factors for metabolic disease in adulthood. Sci Adv. 2018 Jan 31;4(1):eaao4364. DOI: 10.1126/sciadv.aao4364

Mapping the food universe

Projects such as the Foodome Project are now attempting to catalogue this hidden chemical universe. More than 130,000 molecules have already been listed, linking food compounds to human proteins, gut microbes and disease processes. The aim is to build an atlas of how diet interacts with the body, and to pinpoint which molecules really matter for health.¹⁵⁾Menichetti G et.al. Chemical Complexity of Food and Implications for Therapeutics. N Engl J Med 2025;392:1836-1845 DOI: 10.1056/NEJMra2413243

The hope is that by understanding nutritional dark matter, we can answer questions that have long frustrated nutrition science. Why do certain diets work for some people but not others? Why do foods sometimes prevent, and sometimes promote, disease? Which food molecules could be harnessed to develop new drugs, or new foods?

We are still at the beginning. But the message is clear – the food on our plate is not just calories and nutrients, but a vast chemical landscape we are only starting to chart. Just as mapping cosmic dark matter is transforming our view of the universe, uncovering nutritional dark matter could transform how we eat, how we treat disease and how we understand health itself.

This article is republished from The Conversation under a Creative Commons license. Read the original article.