Bioindividual Nutrition: Why There’s No One-Size-Fits-All Diet

By: Siobhan Gray, MD

Everyone wants the perfect diet.

And everyone’s convinced they’ve found it until it stops working.

Peter Attia calls nutrition “the most frustrating field in medicine,” and he’s right. The data are messy, the variables endless. But the truth isn’t that nutrition science has failed. It’s that we’ve been asking the wrong question.

Not, what's the best diet? But what’s the best diet for you?

Why Nutrition Research Contradicts Itself

Nutrition studies are notoriously difficult to control.

We rely on self-reported food questionnaires (“How many cups of broccoli did you eat last year?”) and attempt to isolate single nutrients in an environment where everything interacts: genes, microbiome, stress, sleep, exercise, hormones, even light exposure.

So when headlines conflict: “Eggs raise cholesterol!” vs. “Eggs lower cholesterol!’” they’re both partly right. Each conclusion applies to some people under some conditions.

Here’s why.

1. Genetics: The Blueprint Beneath the Plate

Your genome shapes how you metabolize fat, carbohydrate, and protein.

- Keto and cholesterol: Roughly 20–30 % of people on ketogenic diets develop large rises in LDL-C and ApoB, sometimes doubling within months.¹ These “hyper-responders” often carry variants in APOE ε4, LDLR, or PCSK9, which increase hepatic cholesterol production or reduce LDL clearance. Others, with APOE ε2 or favorable LDL-receptor function, see neutral or improved lipids on the same macros.

- Carbohydrate tolerance: People with copy-number variations in the AMY1 gene (salivary amylase) digest starch differently. High-copy carriers handle carbs smoothly, while low-copy carriers get larger glucose and insulin spikes from the same potato.²

- Caffeine metabolism: Variants in CYP1A2 determine whether coffee lowers or raises your blood pressure. The same latte can either improve performance or increase your heart-attack risk depending on your enzyme speed.³

Nutrition becomes clearer when you stop viewing it through population averages and start seeing it through molecular individuality.

2. The Microbiome: Your Inner Ecosystem

You are not just what you eat. You are what your microbes do with what you eat.

The gut microbiota determine how we extract calories, produce short-chain fatty acids, metabolize bile acids, and even regulate serotonin and estrogen.

- Eggs and TMAO: Some people’s microbes convert choline (from eggs and meat) into trimethylamine N-oxide (TMAO), associated in certain studies with higher cardiovascular risk. Others lack those microbial genes and make little or none, even on the same diet.⁴

- Fiber and fermentation: A vegan athlete with a diverse microbiome can produce abundant butyrate, fueling colon cells and regulating inflammation. Another person lacking those keystone species may bloat, fatigue, or struggle to absorb nutrients on the identical diet.

Your gut flora is as individual as a fingerprint and it constantly shifts with stress, sleep, antibiotics, and environment.

3. Hormones, Sex, and Stage of Life

Nutrition interacts differently with male and female physiology, and it changes across the lifespan.

- Women often experience greater thyroid sensitivity to carbohydrate restriction. Prolonged low-carb diets can lower free T3 and raise cortisol, causing fatigue and menstrual changes.⁵

- Post-menopausal women metabolize fat differently due to lower estrogen and reduced lipoprotein-lipase inhibition, sometimes making higher-fat diets more effective for satiety and glucose control.

- Older adults require more protein (≥1.2 g/kg/day) to offset anabolic resistance and preserve muscle mass.⁶

The same macros that sculpt a 30-year-old triathlete can stall recovery or bone density in a 55-year-old woman.

4. Epigenetics and Metabolic Memory

Gene expression is not fixed. It is dynamic, responsive, and alive.

Every meal, every night of sleep, every season of stress leaves a biochemical fingerprint.

Through mechanisms like DNA methylation, histone acetylation, and micro-RNA signaling, diet and lifestyle choices continuously modify how our genes are read and expressed. These changes don’t alter the genetic code itself, but they do influence which genes are switched on or silenced.

What’s even more extraordinary is that these patterns can echo across generations. Your grandmother’s famine, your mother’s stress during pregnancy, even your own early childhood nutrition can leave molecular imprints that shape insulin sensitivity, fat storage, and inflammatory tone today.⁷ This is the biology of inheritance beyond DNA: epigenetic memory.

Because much of this regulation happens through the gut–brain–immune axis, our microbiome acts almost like an archive, storing experiences, exposures, and environmental cues that influence how genes behave.

What you feed your microbes today can literally rewrite how your genes express tomorrow.

It’s why identical twins diverge metabolically as they age, and why no two nutritional paths ever look quite the same.

Nutrition doesn’t just sustain biology. It edits it.

→ Read more in my related post, “The Gut as an Archive,” on how your microbiome remembers the life you’ve lived.

5. Psychology, Culture, and Connection

Food is never just biochemistry.

It is language, memory, belonging. It is the smell of your grandmother’s kitchen, the rhythm of Sunday dinners, the comfort of coffee shared with a friend. What we eat connects us to family, to culture, to identity.

That’s why adherence is the single most powerful but under-discussed variable in nutrition science. Even the “perfect” diet fails if you can’t or don’t want to sustain it. Studies show that adherence, not macronutrient composition, predicts long-term success in weight management and metabolic health.⁸

Whether it’s low-carb, plant-based, Mediterranean, or something in between, the best diet is the one you can maintain joyfully and consistently over years, not weeks.

And that has as much to do with psychology as physiology.

When eating becomes restrictive, isolating, or moralized, when it separates you from the people and experiences that give your life richness, it creates a chronic stress response. Elevated cortisol, disordered hunger cues, and emotional depletion follow. Over time, the biological cost of rigidity can outweigh the metabolic benefits of any specific plan.

In contrast, eating with awareness and alignment activates the parasympathetic nervous system, the “rest and digest” state that allows for nutrient absorption, immune regulation, and calm. Shared meals, gratitude rituals, and mindful eating practices literally shift vagal tone and blood-glucose response.⁹

Food isn’t only about what you remove. It’s about what you invite in: pleasure, presence, and connection.

Health is not merely the absence of disease. It’s metabolic coherence with your values and your life.

So What’s the “Right” Diet?

There isn’t one. But there is a process:

1. Start with data: labs (ApoB, glucose, CGM, insulin, hs-CRP), maybe genomics or microbiome testing.

2. Experiment deliberately: adjust macros, meal timing, or food quality; retest in 8–12 weeks.

3. Listen to your lived data: energy, sleep, mood, digestion, performance, community connection.

4. Integrate ethics and enjoyment: a diet that conflicts with your identity will never be sustainable.

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The Takeaway

There are countless ways to be healthy.

Find the one that aligns your physiology with your peace, where you feel energized, connected, strong, and true to your values.

Because food isn’t just fuel. It’s information, relationship, and ritual.

And the only diet that truly works is the one your body and your conscience both say yes to.

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References

1. Norwitz N.G., et al. Curr Opin Lipidol. 2021;32(6):405-413.

2. Usher C.L., et al. Nat Genet. 2015;47:921-925.

3. Cornelis M.C., et al. JAMA. 2006;295(10):1135-1141.

4. Wang Z., et al. N Engl J Med. 2011;364:1575-1584.

5. Sarzynski M.A., et al. J Clin Endocrinol Metab. 2019;104(2):370-386.

6. Deutz N.E., et al. Clin Nutr. 2014;33(6):929-936.

7. Dominguez-Salas P., et al. Am J Clin Nutr. 2014;100(6):1825-1831.

8. Hall K.D., et al. BMJ. 2019;366:l4897.

9. Meier A., et al. Nutrients. 2021;13(2):546.

North Reflection Prompt

What’s the way of eating that feels coherent for you, one that nourishes your body and reflects your values?

Where do joy, connection, and physiology meet on your plate?