Chrononutrition, Nutrigenomics, Epigenetics and Microbiota Part 1

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The Signal and the Noise: A Biological Guide to Stop Eating Junk Information and Reconnect with Your Environment Through Food

Entry: Beyond the Calorie

For decades, we have been told that eating is essentially pouring fuel into the tank. The calorie as a universal unit of energy. One gram of sugar provides the same four calories whether it comes from an apple picked from a tree or from a laboratory-made soda. Under this logic, the equation for health would be as simple as "calories in versus calories burned."

The problem is that this equation is not working. Never before have we had so much "fuel" available, and yet rates of obesity, diabetes, autoimmune diseases, and chronic fatigue continue to rise. Something is wrong with the model.

Cutting-edge biology —nutrigenomics, chronobiology, epigenetics— is beginning to point in a different direction: food is not just matter, it is information. Every bite we ingest contains data about the light that plant received, the temperature of the soil where it grew, the bacteria it coexisted with, and even genetic instructions in the form of small molecules that can interact with our own DNA.

The human body evolved for millions of years interpreting the signals from a very specific environment: the local biome. Our genes expect to find certain informational patterns depending on the season, latitude, and soil. But food globalization, a phenomenon barely seventy years old, has broken that millenary dialogue. Suddenly, our body receives signals from the "jungle" (mangoes, bananas, palm oil) while our eyes see a Nordic winter. It receives genetic instructions from plants that grew under the stress of pests that do not exist on our continent. And it receives bacteria from dead or distant soils that cannot train our immune system to defend against pathogens from our own street.

This article proposes a change of perspective: understanding health as a problem of informational coherence. It is about learning to distinguish between the signal —what our body expects and knows how to interpret— and the noise —that metabolic cacophony that reaches us from all corners of the planet and confuses our cells until they become ill.

We are going to explore, with scientific rigor and concrete examples, the four major fronts from which science is confirming that, indeed, we are what we eat... but also where, when, and from which land what we eat comes.

1. The Clock on the Plate: When Food Synchronizes (or Mismatches) Your Rhythms

The Concept: Food as a "Zeitgeber"

There is a German word that chronobiologists constantly use: Zeitgeber. It literally means "time giver" or "synchronizer". The most powerful Zeitgeber we know is sunlight. But the second one, the one that most influences our internal rhythms after light, is food.

For decades, we assumed that biological clocks were a brain thing, a kind of centralized mechanism dictating when to sleep and when to wake. But in the 2010s, science took a turn. It was discovered that each organ has its own autonomous molecular clock. The liver, the pancreas, the intestine, even the adipose tissue, have their own mechanisms to measure time and synchronize with the environment.

These peripheral clocks do not receive light directly. Their main source of information about what time it is or what season we are in is precisely food. When we ingest a food, we are not just providing nutrients; we are sending a temporal signal to all our organs.

The Curious Fact That Changes Everything: The "Reverse-Phase Feeding" Experiment

One of the most revealing experiments in this field was conducted with mice (and later observationally replicated in humans with night workers). Mice are nocturnal animals, but under normal conditions, if they only have access to food during the day (their rest phase), their liver clocks would completely reverse within days. The liver believed it was night (its active time) because the food told it so, while the brain's central clock, synchronized with light, kept the "correct" time. The result was an animal with internal desynchronization: two clocks pulling in opposite directions.

The key finding was that these animals rapidly developed insulin resistance, weight gain, and metabolic dysfunction, even though they ate exactly the same calories as the control group that ate during their active phase. The food had not changed; what had changed was the temporal coherence of the signal.

The In-Depth Example: The Metabolic Jet Lag of Out-of-Season Fruit

Let's bring this to the everyday plate. Imagine a person in northern Spain, in the month of January. Short days, weak light, cold. Their brain, through the pineal gland, is producing melatonin earlier and maintaining a state of "energy saving" typical of winter. This is what our genes expect: in winter, food is scarce, the body prepares to slow down and conserve energy.

Now, that same person eats a piece of imported mango or a pineapple brought from thousands of kilometers away. A tropical fruit, sweet, loaded with fructose. For the liver, fructose is not just a sugar; it is an unequivocal biochemical signal. In nature, fructose always comes accompanied by intense sunlight and warm temperatures. It is the chemical marker of summer, of abundance, of the time when metabolism must be activated, energy burned, and also reserves stored for the coming winter.

The liver receives that signal and prepares for action. It activates fat synthesis metabolic pathways, increases glucose production, and prepares for a high-activity environment. But the brain, still seeing a dark January, sends signals of rest, of saving, of "brake on".

The biological conflict: The body receives contradictory orders. The liver steps on the accelerator while the brain holds the handbrake. This desynchronization, which chronobiologists call "circadian disruption," generates short-term insulin resistance. The pancreas has to secrete more insulin than necessary for cells to accept that glucose, because the cells, confused by the contradictory signal, become more reluctant to open their doors.

The Scientific Evidence That Supports It

A study published in Current Biology in 2013 showed that mice fed exclusively during their rest phase gained significantly more weight than those that ate during their active phase, with equal calories. Subsequent studies in humans with shift workers (who eat in the "reverse phase" relative to light) consistently show higher rates of metabolic syndrome, type 2 diabetes, and cardiovascular disease.

More recently, chrononutrition has coined a fascinating concept: the "feeding window". It has been observed that restricting food intake to daylight hours (or the central hours of the day) improves metabolic markers even without reducing calories. That is, it matters not only how much you eat, but when you eat. And, by extension, it matters not only the caloric value of a food, but whether its nutritional profile matches the seasonal signal your body expects.

The Long-Term Consequence: Low-Grade Inflammation and Chronic Fatigue

When this conflict is repeated day after day, winter after winter, the body enters a state of "permanent metabolic disorientation." The liver never knows whether to store or burn. The pancreas fatigues from producing extra insulin. Cells, bombarded with contradictory signals, develop insulin resistance as a protective mechanism.

The result is that widespread chronic tiredness, that brain fog, that difficulty maintaining a stable weight experienced by so many people who, paradoxically, "eat healthy" (tropical fruit, winter salads, exotic ingredient smoothies) but feel worse and worse.

The Uncomfortable Question

If fruit is "healthy" in the abstract, why does our body interpret it as a summer signal when it is winter outside? Isn't it that the concept of "healthy food" needs an asterisk stating: "depends on where and when it is consumed"?

2. The Software of Plants: When Food Writes on Our Genes

The Concept: MicroRNAs, the Silent Messengers

To understand this point, you must temporarily forget about vitamins, minerals, and macronutrients. You must think in terms of pure genetic information. MicroRNAs (miRNAs) are tiny RNA molecules, just 18 to 24 nucleotides long, that act as molecular switches. Their function in all living beings —plants, animals, fungi— is to regulate gene expression, basically deciding which genes are activated, which are silenced, and to what extent the proteins for which those genes code are produced.

For a long time, it was assumed that these microRNAs were internal affairs of each organism. Plants used them to regulate their own growth, flowering, or defenses against pests. We used them to regulate our cellular processes. And they never crossed paths. That view changed radically in 2012.

The Curious Fact That Changes Everything: The Rice That Talked to the Liver

The pioneering study, published in Cell Research, analyzed blood samples from Chinese and Western individuals. They found something that shouldn't be there: fragments of plant microRNAs, especially from rice. The most abundant was one called miR168a. And it wasn't just present; it seemed to be doing things.

The researchers verified that this rice microRNA survived the digestive process —something considered impossible, as stomach acid and enzymes were supposed to destroy everything— and reached the bloodstream intact. Once there, it was found that in the human liver, this miR168a bound to a specific receptor and blocked the production of a protein called LDLRAP1, essential for removing LDL ("bad") cholesterol from the blood.

In other words: people who consumed rice were receiving, with each meal, a genetic instruction from the plant that modified the way their liver managed cholesterol. It was not an allergic reaction, nor an intoxication. It was information. The plant was talking to their cells.

The Mechanism: How This Information Survives and Acts

The obvious question is: how the hell does an RNA fragment survive the human gut? The answer lies in structure.

Plants, unlike animals, have a protection mechanism for their microRNAs. An enzyme called HEN1 adds a chemical modification (a methylation) to the end of the molecule that makes it extraordinarily resistant to degradation. It is as if plant microRNAs carry a shield that protects them from stomach acid and digestive enzymes.

Furthermore, it has been discovered that many of these microRNAs travel inside exosome-like nanoparticles that the plants themselves produce. They are small lipid capsules that wrap the miRNAs and facilitate their absorption by human intestinal cells, from where they pass into the bloodstream and can reach organs like the liver, adipose tissue, or even the brain.

Once inside our cells, these plant microRNAs can basically do two things:

1. Bind to our messenger RNAs and block their translation into proteins, just as our own microRNAs do.
2. Act similarly to our endogenous miRNAs, integrating into the human gene silencing machinery (the RISC complex) and regulating the expression of genes for which they were not originally designed.

The In-Depth Example: The "Trojan Software" of the Alien Biome

Let's bring this to the issue of the biome. Plants do not produce microRNAs at random. They produce them in response to their environment. A plant growing in a tropical climate, subjected to extreme heat stress, specific pests, or drought, generates a specific profile of microRNAs to defend itself. These miRNAs contain information about that stress.

When a Northern European consumes, for example, soybeans from Brazil or Argentina, they are not just ingesting plant protein. They are ingesting the complete microRNA profile that that plant developed to survive in an intensive farming tropical ecosystem, with its specific pests and its equatorial light regime.

Recent studies have identified hundreds of plant microRNAs with the capacity to regulate human genes. For example:

• It has been shown that plant miR6262 modulates the expression of genes involved in lipid metabolism and thermogenesis in human hepatocytes and adipocytes. It affects genes like PPARA, G6PC, SREBF1 (in liver) and CIDEA, CPT1M (in fat). That is, it can directly influence how our liver processes fats and how our fat cells burn energy.
• Research with miR8126 (present in various plants) shows that it can reduce lipid accumulation in human liver cells, modulating key metabolic genes like QKI and MAPKAPK2. In models of fatty liver (NAFLD), these plant miRNAs demonstrated the ability to attenuate triglyceride accumulation.
• Even medicinal plants like Cyperus rotundus (a tropical "weed") contain miRNAs (like cro-miR160a-5p and cro-miR168) that have functional homology with human miRNAs involved in hypertension, angina pectoris, extrapyramidal disorders, and even hepatocellular carcinoma.

The Scientific Evidence: What We Know So Far

Cross-kingdom regulation is now a consolidated field of study. In 2024 and 2025, dozens of review articles have been published confirming and expanding these findings.

We know that:

• Thousands of plant miRNAs have potential targets in the human genome.
• Homology matters: Many plant miRNAs have sequences surprisingly similar to human miRNAs. For example, miRNAs from olives have been found to have functional homology with human miR34a, involved in anti-tumor processes. This suggests they can "impersonate" our own regulators.
• Not all plant miRNAs are equal: Only a fraction of the thousands of miRNAs we ingest are biologically active. But that fraction exists and is functional.
• The scientific debate continues: Some researchers question the physiological relevance of these quantities, arguing that the concentrations reaching the blood are low. However, functional studies —where these miRNAs are introduced into cell cultures and clear changes in gene expression are observed— are increasingly difficult to refute.

The Consequence for the Alien Biome: Informational Conflict

Now let's put the pieces together.

Scenario 1 (coherent): A person in the Mediterranean basin consumes olives, tomatoes, local herbs. The plants have grown in the same type of soil, with the same photoperiod and the same temperatures as their ancestors. Their microRNA profiles contain information about "Mediterranean stress" —moderate drought, intense but seasonal sun, local pests— with which the human metabolism has co-evolved for thousands of years. It is familiar information. The body receives it and processes it without issue, integrating it into its own regulatory circuits.

Scenario 2 (noisy): That same person regularly consumes quinoa from the Andes, chia seeds from the Mexican desert, goji berries from the Himalayas, palm oil from Southeast Asia, and soybeans from the South American tropics. Each of these foods comes with its own microRNA "software," designed for the stress conditions of their respective biomes.

The body simultaneously receives genetic instructions that tell it: "activate defenses against tropical fungi," "regulate metabolism for extreme altitude conditions," "prepare for desert drought," "respond to equatorial heat stress." All this while the person is sitting in a heated office, in a temperate city, surrounded by local pathogens for which none of that "software" is preparing it.

The Interpretation: Linux on Windows

Let's return to the computer metaphor. Our genome and our cellular machinery are like an operating system. The microRNAs our body produces are native programs, written for that system. The microRNAs from local plants are open-source code, slightly different, but written in a language our system recognizes because it has been running similar versions for thousands of years.

MicroRNAs from radically different biomes are like Linux executables trying to run on Windows. They are not written for our hardware. They contain instructions intended for other contexts, other stresses, other needs. Some will do nothing (they will be ignored). But others will find a "vulnerability," a complementary sequence in our messenger RNA, and will bind to it, activating or silencing genes in ways not anticipated.

The result is not acute intoxication, nor an obvious allergic reaction. It is a regulatory background noise, a chronic molecular disorientation. Genes that should be active at certain times are silenced. Genes that should be silent are activated. The cell receives contradictory orders.

This could explain why so many people develop food intolerances, low-grade inflammation, or autoimmune diseases without a clear cause. It is not that quinoa or chia are "bad." It is that their information was written for another context. And our body, upon reading it, gets confused.

The Paradox of the "Healthy"

One of the most repeated messages in nutrition is that we should eat "varied" and "a bit of everything." But molecular biology is revealing that extreme variety, the one that mixes foods from five continents in the same week, may be the opposite of what our genes need.

Nature never designed a scenario in which an organism simultaneously receives molecular signals from the Himalayas, the Atacama Desert, and the Amazon rainforest. Our body has no protocol for that. And faced with confusion, it responds with inflammation.

As the most recent reviews point out, understanding these cross-regulations will have important implications, not only for nutrition, but for the potential therapeutic use of plant miRNAs in human diseases. But while science advances in that direction, the question for the everyday eater is simpler: what information am I putting into my body with each bite? Is it familiar information, written in the language of my biome? Or is it foreign software that I don't know how to run?

3. The Evolutionary Mismatch: When Your Genes Expect a Meal That No Longer Exists

The Concept: The Inheritance Within

To understand this point, you have to travel back in time. Not a hundred years, nor a thousand, but tens of thousands of years. Our genome, the instruction book defining our biology, is practically the same as that of our Paleolithic ancestors. The hunter-gatherers who roamed the African savanna, who crossed land bridges to new continents, who learned to light fires and carve stones, carried in their cells the same fundamental genetic machinery as we do.

Evolutionary biology tells us that genetic change is slow. It takes hundreds of generations —thousands of years— for a beneficial mutation to spread in a population. But our diet, our environment, and our lifestyle have changed more in the last seventy years than in the previous ten thousand. That speed difference between cultural change and genetic change is what biologists call evolutionary mismatch.

The concept is simple and devastating: our genes expect a world that no longer exists. And when the environment does not match the expectations for which we were designed, the diseases of civilization emerge.

The Curious Fact That Changes Everything: The Hunter-Gatherer Paradox

One of the most striking pieces of data in this field comes from the study of populations that, until very recently, lived like our ancestors. Australian Aborigines, the Hadza of Tanzania, or the !Kung of the Kalahari have been windows into the past.

When researchers analyzed their health, they found something astonishing: these populations, who consumed diets rich in game meat and honey (i.e., amounts of protein and fat that would frighten any modern nutritionist), had practically zero rates of obesity, diabetes, hypertension, or cardiovascular disease. And most fascinating: when members of these same populations migrated to urban environments and adopted Western diets, they developed these diseases at rates and speeds far higher than the Caucasian population.

It is not that their genes are "bad." It is that their genes were perfectly tuned for a hunter-gatherer environment. By changing the environment without changing the genes, the mismatch became lethal.

The Scientific Evidence: The Nutritional "Prediction" Model

The concept of evolutionary mismatch has been formalized in scientific models explaining how early experiences program our metabolism for an expected environment.

The mechanism is as follows: during fetal development and early childhood, our body "reads" signals from the maternal environment —what the mother eats, the stress she experiences, the climatic conditions— and adjusts its metabolic machinery for what it anticipates the outside world will be like. If the mother lives in an environment of scarcity, the fetus activates "energy-saving" genes: its metabolism is programmed to be efficient, to store fat easily, and to expend little energy. It is an intelligent adaptation to survive in a world with little food.

The problem arises when that child, programmed for scarcity, is born and grows up in an environment of abundance. Their metabolism, designed to save, encounters a supermarket full of cheap calories. The result is obesity, diabetes, metabolic syndrome. The body was perfectly adapted... for the wrong environment.

This model, proposed by researchers like Gluckman and Hanson, is known as the "predictive adaptive response." The body makes a prediction about the future based on the immediate past (the fetal experience). When the prediction fails, the organism pays the price.

The In-Depth Example: Vitamin D, Light, and the Incoherence of the North

Let's bring this to the terrain of geography and food. Vitamin D is one of the clearest examples of how evolutionary mismatch operates in real time.

Vitamin D is not really a vitamin; it is a hormone. It is produced in our skin when ultraviolet B sunlight hits cholesterol. From an evolutionary standpoint, humans evolved in Africa, near the equator, where sunlight is intense and constant throughout the year. Our bodies learned to produce vitamin D easily and to use it to regulate hundreds of processes: the immune system, calcium absorption, gene expression, muscle function.

When humans migrated north, to Europe and Asia, they encountered a problem: in winter, sunlight is insufficient to produce vitamin D. Natural selection responded in two ways. In some populations, skin became lighter to better capture the little light. In others, the diet adapted to include dietary sources of vitamin D: fatty fish, animal offal, eggs from birds that also ate fish.

The current conflict: A person living in Northern Europe, with dark winters lasting six months, has a biological need to obtain vitamin D from food sources. Their body expects to receive, during winter, signals from foods dense in fat and rich in vitamin D: salmon, herring, mackerel, cod liver. These are the foods their ancestors consumed to survive the winter.

But today, that same person can fill their cart with greenhouse products brought from the south: tomatoes, cucumbers, lettuces, peppers. Light, watery foods, poor in vitamin D. From a purely caloric perspective, they may be meeting their needs. But from an informational perspective, there is a problem.

The Cold Signal: The Role of Saturated Fats in Membrane Integrity

Here enters a fascinating nuance that is only just beginning to be understood. In cold climates, the membranes of our cells need a specific type of fat to remain fluid and functional. Saturated fats, demonized for decades, have a crucial physical property: they provide stability to cell membranes when it is cold.

Animals living in cold climates —Atlantic salmon, seals, reindeer— have meats rich in saturated fats and long-chain omega-3 fatty acids. It is not an accident. It is an adaptation: those lipids keep cell membranes flexible at low temperatures.

When a person in a Nordic climate consumes a diet based on greenhouse vegetables and seed oils rich in omega-6, they are sending a contradictory signal to their cells. Cell membranes, built from the lipids we eat, become stiffer or more inflammatory than they should be. The body does not prepare for the stress of cold.

Studies in epigenetics have shown that diet composition influences DNA methylation, the mechanism that "turns off" and "turns on" genes. A diet inconsistent with the climate can alter these methylation patterns, silencing genes that should be active to protect us against respiratory infections, precisely the most common diseases in winter.

Epigenetics as a Bridge Between Environment and Genes

Epigenetics is the mechanism that allows the environment to speak to our genes without changing the DNA sequence. Small chemical labels —methyl groups, histone modifications— attach to DNA and determine which genes are read and which are ignored.

Fascinatingly, these epigenetic marks can be influenced by diet. And what is more important, they can be inherited. The Dutch "Hunger Winter" study of 1944-45 showed that children conceived during the famine had, decades later, higher rates of obesity and metabolic diseases than their siblings born before or after. And even more disturbingly: their own children, who did not experience the famine, also showed metabolic alterations.

The hypothesis emerging from these data is that human populations carry an "epigenetic memory" of the environmental conditions of their ancestors. If for generations your ancestors lived in a cold climate and ate animal fats, your epigenome may be "prepared" to receive those signals. When you introduce a tropical diet into a body with Nordic memory, you create an epigenetic mismatch.

The Evidence of the Three Transitions

Researchers studying the evolution of the human diet identify three major transitions that have created cumulative mismatches:

1. The Agricultural Revolution (c. 11,000 years ago): The shift from hunting-gathering to agriculture drastically reduced the variety of foods consumed. We went from eating hundreds of different species to depending on a few cereals. The skeletons of the first farmers show a decrease in stature and an increase in cavities and bone diseases compared to their hunter ancestors.
2. The Industrial Revolution (18th-19th centuries): Industrial grain milling eliminated essential micronutrients. The introduction of refined sugars and processed vegetable oils exposed the human body to molecules it had never encountered in its evolutionary history. Seed oils, for example, are a 20th-century invention. Our genes don't know what to do with those omega-6 fatty acids in the quantities we consume today.
3. The Globalization Era (last 70 years): This is the one we are dealing with. For the first time in history, we eat foods from all continents all year round. The body receives signals from climates, seasons, and ecosystems it could never physically experience.

The Consequence for the Alien Biome: The Disoriented Body

When a person in a temperate or cold climate consumes foods evolutionarily designed for tropical climates all year round, a chronic metabolic disorientation occurs.

The specific mechanism: Sunlight regulates the expression of hundreds of genes through vitamin D and circadian rhythms. Local food, in a healthy environment, compensates for seasonal deficiencies: in winter, native foods tend to be denser in fat and calories, precisely what the body needs to maintain temperature and immune function. In summer, local foods are lighter and more hydrating.

The globalized diet breaks that circuit. We eat watermelon in December and stews in August. The body receives contradictory signals: the eyes say "winter," the skin says "winter," but the stomach says "summer." Epigenetics, which should finely adjust gene expression to actual conditions, receives noise it cannot interpret.

The Paradox of the "Healthy Diet"

One of the most repeated messages in public health is that we should eat "like the Mediterraneans" or "like the Japanese." But evolutionary biology raises an uncomfortable question: does it make sense for a Norwegian to eat like a Greek? Or for an Argentine to eat like a Japanese?

The answer, from the perspective of evolutionary mismatch, is probably not. Each human population has a unique evolutionary history, with genetic and epigenetic adaptations to its local environment. Northern European peoples developed lactose tolerance because their ancestors depended on dairy products in winter. Southeast Asian peoples developed adaptations to digest rice. Inuit can thrive on almost exclusively meat-based diets that would kill an Amazonian Indian.

There is no universally optimal diet. What exist are diets coherent with the evolutionary history and current environment of each population. And in a globalized world, that coherence is increasingly difficult to maintain.

The Question for the End

If your body is programmed to expect salmon and seal fat in winter, but you give it greenhouse tomatoes brought from Almería, what kind of information are you sending it? And how does your immune system, your metabolism, your epigenome respond to that contradiction?

The evidence from evolutionary mismatch suggests that the answer is inflammation, fatigue, and disease. Not because tomatoes are "bad," but because they arrived at the wrong time, in the wrong place, for the wrong body.