Why Your Diet Isn't Working — And Why It Might Be Your DNA Introduction

Well, hey everyone. Welcome back to my YouTube channel and Pushing the Limits podcast. And if you're new here, welcome. My name is Lisa Tamati. For those who don't know me yet, I spent over 25 years as a professional ultra-endurance athlete — running across deserts, through Death Valley in the middle of summer, and competing in some of the most brutal multi-day races on the planet, from the Sahara to the Gobi and all over the place.

I've spent my life pushing the absolute edge of what the human body can do. But here's the thing about spending that long at your limits — you become really obsessed with understanding the machinery, the body. What makes one person recover faster? Why does one athlete crumble under the same conditions while another thrives? And why does the same training protocol produce elite performance in one person and injury and breakdown in another?

That obsession with individual human performance is what led me eventually away from competition and into the world of functional and cellular medicine, longevity science, and health optimization. Because I realized the questions I was asking on the racecourse were the same questions that people were asking in their daily life — just at different intensities.

But honestly, what really changed everything for me was not a race — it was my mom. Those who know me and my channel will know a little bit about her story. She suffered a massive aneurysm and was given absolutely no chance of getting back to full capacity again. We were told she'd be like a vegetable — put her into an institution. She had massive, severe brain damage. She couldn't walk or talk or do anything.

It took me years of studying and researching to get everything back to full recovery. I got her back to getting a full driver's license, full power of attorney — an incredible story. I wrote about that in my book, Relentless. And that's what really drove me into things like brain regeneration and all that sort of stuff.

Why I'm Passionate About Personalized Health

So what I want to do today — because I really am passionate about people understanding how their body works — is share what I've learned along this 11-year journey. It's not just about diet and it's not just about any one thing. Genetics play a huge role, and you could be doing something that's actually harming you, thinking that you're doing something right.

I want to use a little bit of a case study from my clinical practice. It's all anonymized obviously, but we'll call her Anna. That's not her real name, but it is her story. And I'm sharing it because it's about helping one person stop blaming themselves for something that isn't their fault.

So if you feel like you're banging your head against a brick wall, this story is for you.

Anna's Story

Anna was a lady in her late 40s — very intelligent, health-conscious. She came to me having gained a lot of weight over a short period of time despite eating really well, or what she thought was well. She'd gone full keto, done the exercises, done all of the things.

She'd gone properly keto — had done the research, followed the practitioners and the influencers that she trusted, cut the carbohydrates right down, loaded up on the healthy fats, tracked her macros, and stayed in ketosis. She was committed.

But the weight kept creeping on. Her energy was inconsistent. Her blood glucose wasn't improving the way that keto was supposed to improve it. She was starting to feel like a failure — like there was something fundamentally broken about her body, or her willpower, or both.

I want to really sit with that for a moment, because I think a lot of people watching this may have a similar story. You're doing everything the books or the influencers say and it's not working. And the only conclusion that the diet industry ever seems to offer you is that you must be doing something wrong — you're eating too much, there's always some simple answer like "more calories" or something of that nature.

But Anna wasn't doing anything wrong. The diet was wrong for her. Not wrong in the abstract — keto is a legitimate therapeutic dietary approach that I often use for people and that genuinely helps — but wrong for her specific biology, in a way that was completely predictable once we looked at her genetics.

But no one had ever looked at her genetics.

The Problem With One-Size-Fits-All Diet Advice

Before I get into the specifics of what we found, I want to talk about something that I think is genuinely important, and I'll be direct about it because that's how I operate.

We're living in a golden age of health information, but also misinformation — or advice that's dressed up as health information. And the two are often impossible to tell apart.

Here's how it typically unfolds. Someone — an influencer, an athlete, a podcaster, maybe even a well-credentialed doctor — discovers a dietary approach that transforms their health. They lose 20 kilos. Their autoimmune condition goes into remission. Their mental clarity doubles. Their energy becomes extraordinary. And they are telling the truth — that happened to them.

So they share it, and they absolutely should share it. But what they almost never say — what the before-and-after never captures — is: "This worked for me because of my specific genetics, my hormone profile, my gut microbiome, my stress history, my age, my activity level, and about 40 other variables that I have no idea whether you share."

What they say is, "This worked for me. Try it." And millions of people do. And some of them — the ones whose biology happens to closely match the person sharing those great results — they succeed. Those people become the testimonials, the success stories.

But the people it doesn't work for? They quietly disappear. They feel like failures and they move on to the next trend.

I've watched this cycle play out across every major dietary movement of the last 20 years — low-fat, high-fat, raw, vegan, carnivore, paleo, keto, intermittent fasting. Every single one of these approaches has real, legitimate science behind it. Every single one works extraordinarily well for some people. And every single one, if applied to the wrong biology, is somewhere between ineffective and actively harmful.

The fundamental problem is not a lack of nutrition science. We actually know a lot about how diets affect human health. The problem is that we keep applying population-level research to individual-level situations.

You are not the population. You are a specific, unique biological system with a particular set of genetic instructions, a particular hormonal environment, a particular gut ecosystem, and a particular history of stress and illness and recovery.

Treating you with population-level diet advice is like prescribing the same medication dose to every person regardless of their weight, their liver function, their other medications, or their genetic variance in drug metabolism. We wouldn't accept that in pharmacology. We shouldn't accept that in nutrition.

What Anna's DNA Revealed

So let's get into exactly what Anna's DNA revealed, because this is where the science gets fascinating. This is just one example of why DNA is so powerful and so interesting and how it can affect you. There are many, many more examples, but this is hers.

When we ran her comprehensive genetic panel, three variants in her metabolic genes came up that together told an absolutely clear story about why keto in particular was the wrong approach for her.

PPARα (PPAR Alpha)

The first gene was called PPARα. PPARα is essentially the master regulator of fat metabolism. It governs how efficiently your body uses fat as fuel, particularly saturated fat.

Anna carried a variant in this gene that is specifically associated with abnormal lipid metabolism on high-saturated-fat diets. In plain language, that means the genetic machinery you need to efficiently burn the fats that form the foundation of a ketogenic diet — well, Anna was running at significantly reduced capacity.

When you feed a body like Anna's a classic ketogenic diet, even a well-formulated one, the fat doesn't get burned the way the textbook says it should. Lipid metabolism becomes dysregulated. The fat isn't efficiently oxidized for energy — instead, it gets stored. Blood lipid profiles can shift in directions that increase cardiovascular risk rather than improving it. This is the opposite of what keto is supposed to do. And it's directly predicted by this one genetic variant.

ACSL1

The second variant was a gene called ACSL1. ACSL1 is involved in how your body handles saturated fat in relation to blood glucose regulation. Anna carried the homozygous variant — meaning both copies of the gene carried the change — which is associated with elevated fasting glucose specifically in response to high saturated fat intake.

Here's the irony of Anna's situation. She had gone keto partly because she was concerned about her blood sugar trending in the wrong direction. She was trying to protect her metabolic health. But because of her ACSL1 genotype, high saturated fat was actively raising her blood glucose. The diet she chose to fix the problem was making it worse. Not because she was doing it wrong, but because her genetics were wired differently to the people the advice was designed for.

APOA2

Then there was the third variant — APOA2. APOA2 is a gene involved in how your body responds to saturated fats in terms of body composition. Anna carried the homozygous form, associated with significantly higher BMI when saturated fat intake exceeds approximately 22 grams a day.

To put that into context, 22 grams of saturated fat is roughly two tablespoons of butter or about 150 grams of fatty meat. On a standard keto diet, you might consume that by mid-morning.

The Compounding Effect

Here's what's critical to understand about these three variants taken together. Each one individually might be manageable. Someone with a PPARα variant might tolerate keto with some tweaks. But when you stack PPARα, ACSL1, and APOA2 — all three working against saturated fat metabolism simultaneously — the effect compounds. These genes don't just add, they multiply the problem.

Anna wasn't just slightly wrong for keto. She was, from a genetic standpoint, one of the worst possible candidates for a traditional high-saturated-fat approach. And no amount of discipline, tracking, time-restricted eating, or trying harder would change this — because it wasn't a behavior problem. It was a biology problem.

What Anna Actually Needed

Now importantly, these variants don't mean Anna can't eat fat. They don't mean she needs to go low-fat or avoid avocado and nuts. What they mean is that she needs the right kinds of fat — predominantly monounsaturated fats. Olive oil, avocados, macadamia, omega-3-rich fats from oily fish — rather than the high saturated fat load of butter, cream, and fatty meat that defines classic keto.

Her carbohydrate genetics were actually quite robust. Her insulin response genes were strong. Her body handles moderate complex carbohydrates well. So the diet that actually fits Anna's genetic blueprint is closer to a Mediterranean pattern — quality protein, predominantly unsaturated fats, moderate complex carbohydrates from whole food sources, and abundant veggies. The exact opposite of what she'd been doing for a year.

Once she shifted to that approach, the weight started moving within weeks. The glucose started improving. The energy became more consistent than it had been in years. Not magic, not a miracle protocol — just eating for the body she actually has.

The Gut: The Layer Most People Miss

Here's where Anna's story gets even more interesting. This is the layer that most people never look at, even when they're doing what they think is comprehensive health testing.

We ran a full microbiome mapping, and when we looked at her results in the context of everything else, there was a very clear story being told.

What Was Good

Let me start with what was actually good, because this matters. Anna's gut was not a disaster zone. Her inflammatory markers were excellent. Her calprotectin — a key marker of gut wall inflammation — was completely normal, well under 50. Her zonulin, which tells us about intestinal permeability (what people call leaky gut), was normal. There were no parasites, no H. pylori, no pathogenic bacteria, no fungal overgrowth at all — no candida, nothing. Her pancreatic function was strong, no signs of malabsorption.

On the surface: clean gut, no red flags. That's what a standard test would pick up.

What Was Depleted

But when you look deeper at the bacterial ecosystem itself, the picture is more nuanced. And this is exactly why standard testing misses these things.

Her total Bifidobacteria count was just 6, sitting at the very floor of a reference range that goes up to 2,000. Three of the four Bifidobacterium species — adolescentis, breve, and longum — were below detectable limits. Only Bifidobacterium bifidum was present, and barely.

Why does this matter? Bifidobacteria are not just "nice to have." They are foundational architects of your gut ecosystem.

• Bifidobacterium adolescentis specifically drives GABA production. GABA is your primary calming neurotransmitter. Low GABA means higher anxiety, poorer sleep quality, and a nervous system that runs hotter than it should. In someone already under significant stress — which Anna was — this is not a small thing.

• Bifidobacterium longum regulates inflammatory cytokines and maintains intestinal barrier function. It has one of the strongest evidence bases for immune regulation of any probiotic species we know of. When it's undetectable, your gut immune interface is operating without one of its key moderators.

Her Lactobacillus picture told a similar story. Low total lactobacilli were present, but the diversity was very poor. L. acidophilus, L. plantarum, L. rhamnosus, and L. salivarius were all below the detection threshold or absent.

L. rhamnosus in particular is worth noting because the research is very clear: chronic psychological stress is one of the primary drivers of Lactobacillus depletion. The gut was reflecting the stress load she'd been carrying.

She was also missing Oxalobacter formigenes entirely — a specialist bacterium whose job is to break down oxalate in the gut. Without it, oxalate accumulates, which over time increases the risk of kidney stone formation and has been linked to inflammatory bowel disease. Not a headline finding, but it's the kind of thing you know about if you're looking.

And then there was Faecalibacterium prausnitzii — one of the most important anti-inflammatory bacteria in the entire gut ecosystem, the one most closely associated with gut health and protection against depression, asthma, and metabolic disease. In Anna's case, it was present but at the very low end of normal. Not a crisis, but not thriving.

The Clinical Picture

Here's how I read this picture clinically. Anna's gut was structurally intact — no inflammation, no infection, no permeability problems. Great, the walls were holding. But the population of beneficial organisms living inside it had been depleted, almost certainly by the combination of chronic stress, a high-fat diet that doesn't selectively feed Bifidobacteria and Lactobacilli (take note, ketogenic people), and the broader disruption that prolonged periods of physiological and psychological strain can cause to the gut ecosystem.

The gut-brain axis runs both ways. A nervous system under chronic stress kills off your beneficial gut bacteria. I know this — I've been under a lot of stress in the last 10 years and I have to be very careful with this. And beneficial gut bacteria produce the neurotransmitters and short-chain fatty acids that regulate your stress response. When you deplete them, the whole system becomes less resilient.

The Metabolic Connection

Here's the metabolic piece that ties everything together. Bifidobacteria and Lactobacilli play a direct role in how your body extracts and processes energy from food. When these populations are depleted, your metabolic regulation becomes less precise, your appetite signaling becomes noisier, and your ability to maintain stable blood glucose between meals decreases.

Anna's metabolic dysfunction wasn't just genetic — it was being compounded by a gut ecosystem that had been progressively depleted and a dietary approach that was doing nothing to rebuild it. A high-saturated-fat ketogenic diet does not preferentially feed Bifidobacteria. It actually tends to starve them. The organisms that thrive on fat-dominant diets are very different to the ones that thrive on a diverse, fiber-rich, polyphenol-rich diet.

And her genetics meant that fat wasn't being burned efficiently anyway. So the combination was working against her on two levels simultaneously.

This is why I never look at genetics alone if I can possibly help it. And why I never look at the microbiome alone if I can possibly help it. It's not always doable to do both tests because they cost money. But if the client is able to, I try to look at both as a holistic picture. You need to see them together alongside hormones and blood work to understand what's actually happening in the whole system.

And then there are other tests too — like organic acids, heavy metals, thyroid, and others — that depending on the case we may bring in.

The Good News

The good news — and there is very good news here — is that Bifidobacteria and Lactobacillus depletion is highly reversible. These organisms respond well to targeted probiotic repletion and to dietary changes that feed them. That's really important — not just the pills, but that you're actually eating diverse plant fibers, resistant starch, and polyphenol-rich foods like berries, olive oil, and dark leafy greens.

And the shift to a Mediterranean dietary pattern that Anna needed for her genetic variants also happens to be precisely the dietary pattern that selectively nourishes Bifidobacteria. The genetics and the gut were pointing to the same solution. That's not always the case — sometimes you're working in multiple directions at once and it gets a bit complex. But when you run all the testing, you do occasionally get that moment where everything points the same way. And that's enormously powerful clinically, because you can move with real confidence.

Hormones, Stress, and What Gets Missed

So we had the genetics, we had the gut, and then we had the hormonal picture and the stress biology. These were the final pieces that explain why things had gotten so difficult so fast.

Anna was going through menopause and was on hormone replacement, but her hormones hadn't been properly optimized.

Her SHBG (sex hormone binding globulin) — which is like the taxi cab, the carrier protein that binds hormones and makes them unavailable to cells — was highly elevated. A significant portion of her estrogen and testosterone was bound and inactive. This is a really important finding. A lot of people go on hormone replacement but they don't look at their SHBG. If SHBG is too high, you're taking the hormone but you're not getting the benefit.

Her thyroid conversion was also suboptimal, and her cortisol rhythm was dysregulated after an extended period of significant loss and grief.

Cortisol at chronically elevated levels does specific, measurable things to your body. It drives visceral fat deposition directly. It raises fasting blood glucose. It suppresses the immune function of the gut. And Anna had genetic variants that made her nervous system more sensitive to stress than average. So the events of the past couple of years hit her physiology harder than they would have hit someone with different genetics.

I use the DUTCH test (Dried Urine Test for Comprehensive Hormones) for this. It's fantastic because it shows you not just hormone levels but how those hormones are actually being metabolized and broken down. You can have normal estrogen levels but profoundly abnormal estrogen metabolism. You can have a cortisol level that looks fine at 9 in the morning — which is usually what doctors test — but is completely flat by midday. You don't see those things in a standard blood panel or a standard one-off cortisol test.

I want to say something clearly here because I think it matters: no diet on earth would have fully worked for Anna without addressing the stress biology at the same time. That's not a lifestyle platitude. It's endocrinology. The hormonal environment that you are living in determines the context in which every dietary choice you make either succeeds or fails.

Universal Principles That Apply to Everyone

Now, I don't want this to feel paralyzing — like you need a full clinical workup before you're allowed to eat dinner. So let me give you the ground-floor principles that I believe apply to virtually anyone regardless of your genetics.

Eliminate Processed Seed Oils

These are the most poisonous, horrible things that I think human beings have ever invented. If you look at the process by which they make things like canola oil, soybean oil, sunflower oil — which have these lovely names — and corn oil, you'd be absolutely horrified. They're high in omega-6 fats in quantities that, when embedded in the modern food supply, drive systemic inflammation.

Omega-6 on its own is not bad — it's the relationship to omega-3s and the sheer amount we're getting. Because omega-6 is much more shelf-stable, that's what all of our sauces and processed foods are made with. You get a massive skew in the ratio of omega-6 to omega-3. That's why I'm so pro a good quality omega-3, or eating lots of fatty fish — it's really important to get that balance right.

Cook with avocado oil (higher smoke point), olive oil for salads and lower-temperature cooking. Butter and ghee are good if you don't have the genetic profiles Anna had. Coconut oil is another option. And avoid deep-fried anything from a commercial kitchen — it's absolutely horrific for the membranes of your cells.

Here's why that matters: the fats you eat become the building blocks of your cell membranes. If you eat too much sugar, you can to some degree burn it off. But fats stick around — they become part of your cellular structure. And membranes are where the brains of the cell are. They're what's letting stuff in and letting stuff out. So when those membranes aren't functioning well, everything downstream suffers.

Eliminate Ultra-Processed Food

Not because the calories are evil, but because ultra-processed food is engineered to override your satiety signals and damages your gut microbiome through emulsifiers and additives that don't exist in nature.

Minimize Simple Carbohydrates and Sugar

As we saw with Anna, not all carbs are equal. Some people's genetics actually favor moderate complex carbohydrates. But nobody's genetics make them well-adapted to refined sugar and white flour in the quantities that modern food delivers them.

Our food supply is a complete disaster. The industrial food complex has engineered things to make you want more, to make you addicted. It gets really hard to get off them once you're in their clutches. Be very careful, especially with your children.

Prioritize Protein

Across virtually every genetic profile, adequate protein supports muscle, metabolic rate, satiety, and long-term health. Most people eat less than they need, particularly women as they age.

Get Your Omega-3s

From food and supplementation — whether through oily fish or a quality supplement. It must be quality, because there are some very poor ones out there that have been extracted with hexane and other things you don't want to know about. Get it from a reputable company, preferably a clinical source. Don't get the ones at the supermarket. You want adequate EPA and DHA — it supports almost every system in your body.

Eat for Your Gut

Diverse plant foods, fiber variety, fermented foods, polyphenols. I had Dr. Ross Pelton on my podcast a couple of times and he did a lecture to my doctor group as well — absolutely amazing. He recommends 6 to 9 cups of vegetables and a little bit of fruit every day, in as wide a variety of types as you can possibly do.

That's a lot — it's quite hard to get to. You might want to start at the bottom and work your way up. But what he's saying is that diversity and variety are very important. This feeds those Bifidobacteria and Lactobacilli that your stress response, immune system, and metabolism depend on.

If you're having problems with your immune system, your gut, or stress levels that you just can't seem to cope with like you used to — do this. These are the universal truths, the floor.

Beyond them — your specific fat composition, carbohydrate quantity, protein sources, supplementation — that's where your individual biology needs to be the guide.

Anna's Outcome

Anna shifted to a more Mediterranean-style approach — predominantly monounsaturated fats, oily fish twice a week, quality protein at every meal, moderate complex carbohydrates from whole food sources, and a dramatic increase in dietary diversity that her gut bacteria desperately needed. Specific prebiotic fibers and polyphenol-rich foods that selectively feed Bifidobacteria became daily staples.

We addressed her hormone replacement — optimized the delivery, improved the balance, ensured her hormones were actually bioavailable rather than bound and inactive.

We dropped her melatonin from 10 milligrams to half a milligram — another genetic finding. I'm a big fan of melatonin, especially for certain conditions, but there's a genetic factor. In her case, a variant in a melatonin receptor gene meant high-dose melatonin was impairing her glucose metabolism overnight. That alone made a measurable difference.

We added a targeted probiotic protocol to begin rebuilding the Bifidobacterium and Lactobacillus populations — specifically the strains that were depleted, because not all probiotics are equal. Supplementing the wrong strains is largely a waste of money. I actually like to give a variety over time — not just the same one bottle. Try to do diversity, especially if you don't know exactly what's depleted.

And then we addressed the stress and grief directly, because no protocol works around unprocessed loss. The body holds onto it. If you can get professional help in that direction, it can be very helpful.

The Results

Within 8 weeks, her fasting glucose had dropped back into the healthy range. In 12 weeks, she had lost 4 kilograms — not from restriction, not from suffering, but from her body finally being in an environment that it could actually work with. Her energy was more stable than it had been in years.

She said to me: "I spent a year thinking I was doing everything right and failing. And now I understand I was doing the wrong thing really well."

Great discipline, great commitment — just doing the wrong things. And that's the difference between generic advice and personalized medicine. That is the direction medicine is heading — personalized medicine in drugs, in supplements, in genetics, in microbiome, in hormones.

That's why I'm so passionate about this — because I know how many people are out there right now working hard, following advice they trusted, and quietly wondering what is wrong with them. Been there, done that, did it for years, for decades, because I had no idea.

Nothing is wrong with you. Your body is doing exactly what its instructions tell it to do. The question is whether you know what those instructions actually say.

Check Out Rejuvenate Pro

I've got a biotech company called Aevum Labs. I spent two years in the formulation of Rejuvenate Pro — a supplement aimed at the aging of your immune system, which is extremely closely linked to your gut health. 70–80% of your immune system is in and around your gut. They are two peas in a pod. If your immune system is going south, you've probably got issues in your gut.

Rejuvenate Pro contains:

• Immune Defense Proteins — a suite of 50+ bioactive whey proteins from the cow that were there to protect the cow from inflammation and infection. They do exactly the same thing in humans.

• Immuno-LP20 — an extract of colostrum (the first food of mammals) with all the fats and components we don't want taken out, so it's very concentrated and very powerful. It helps heal leaky gut and increases transfer factors and growth factors. Both are very beneficial for the microbiome, for Bifidobacteria and Lactobacilli.

• Kawakawa — a native New Zealand herb used for centuries by Māori. It's very gut-protective and helps lower inflammatory cytokines, which increase as you age.

• Carnosic Acid — very good for brain health and cardiovascular health. It lowers something called CXCL9, a chemokine that increases your risk for cardiovascular disease. This was one of the key findings from the 1000 Immunomes Project out of Stanford University and the Buck Institute. Dr. David Furman — who I've also interviewed on my show — led this research over 15 years, the largest immunological study of its kind, examining over a thousand people. They found which markers in the blood are really powerful for understanding how well you are aging in regards to your immune system, which is at the foundational level of all the hallmarks of aging. Carnosic acid is also very beneficial for the brain and for lowering inflammatory cytokines like TNF-alpha, NF-kappa B, interleukin-1 beta, and interleukin-6 — all of which go up as you get older.

If you'd like to check out Rejuvenate Pro, head over to my shop at shop.lisatamati.com. There you'll find not only Rejuvenate Pro but also a curated range of longevity supplements. You can also check out Aevum Labs at aevumlabs.co.nz.

Final Thoughts

Thanks for listening today. I know that was a mouthful, but if you're one of those people struggling with your weight, your energy, stress — not knowing why you're so angry or so depleted — get some proper testing done. Work with a clinician who knows what they're doing and takes a holistic approach. This is functional medicine. This is cellular medicine.

I've been very lucky to have some incredible teachers over the years, especially Dr. Elizabeth Yurth at the Boulder Longevity Institute. Highly recommend you check out her work.

Make sure you personalize everything you do. Try to know what it is for yourself. DNA testing is really, really powerful. If you want to do DNA testing, reach out to me — we can make that happen, especially if you're in New Zealand or Australia. If you're overseas, I can do it as well — it takes a bit more work, but it's doable.

Having your genetics is something that every child on this planet should be given at birth, because it's going to affect you for your entire life. All the other tests are moments in time — snapshots, which are really important — but your genetics, this is something that stays with you forever. It's what you've inherited from your mum and dad. It's like getting a user manual for your body. Really, really powerful.

Thanks for listening today, everybody. Please subscribe, share this with your family and friends, and leave a comment below — it helps the channel. I've been going on this channel now for over 15, 16 years and the algorithm isn't always kind. If you don't mind giving us a like and a share, I really, really appreciate it.

We'll see you on the other side at the next one. Thanks, guys.