Lifestyle Medicine is Clinical Medicine

The six pillars, and the biochemistry beneath them

Part One.

Perhaps you are reading this at work, or before your day begins. Perhaps you are at the end of a very long day. If you are a doctor or healthcare professional, you have cared for patients back-to-back, all day. If you are a curious human who loves science and health, I know you have been a patient yourself. I would like you to meet two of them.

He’s in the waiting room, passing the time on his phone. A new patient. For this man, everything seems to be slipping; his immune system won’t hold, and recurrent infections merge from one into the next. His genuine efforts at diet and exercise are not shifting his persistent weight gain. His cholesterol is inching higher, and he’s only in his late 30s. To look at him, he looks completely fine. He cannot seem to fall asleep, and lies awake for a few hours, then feels exhausted at work. His blood tests are unremarkable.

Across the room, a woman waits for her appointment. She has been here multiple times over 18 months, maybe two years. The deep fatigue she carries is not resolved by sound sleep. Brain fog has become her constant, draining companion; it affects her capacity to think clearly, to the point where she is genuinely worried something is wrong. Bloating, unpredictable digestive dysfunction, unexplained and unconfirmed by any diagnostic workup, has become her new normal. She too looks fine. Her doctor is very happy with her blood test results.

Every consultation they have had was appropriate, thorough and correct.

Both feel frustrated. Both carry a persistent, felt sense that something is not right. As a patient, we struggle to articulate it. As a clinician, we struggle to label or diagnose it, despite having done every investigation necessary.

What have we missed? Even for those of us already practicing Lifestyle Medicine, what, within these consultations is structurally incomplete?

For clinicians in this situation, we have hopefully covered the basics: What time do you go to bed? What is your screen exposure like in the evening? Do you wake overnight, and if so, what happens? What time do you eat your first meal of the day? What do you eat? What is your light exposure in the hour before sleep? These are not complex questions. They are, however, the questions we are most likely to abandon as we reach for the next test to order, the next SNP to screen, the next specialist to refer to. After every possible clinical diagnosis has been eliminated, we are missing a significant opportunity to practice real healthcare, by looking carefully and systematically at how our patients are actually living.

When I told a friend that I had just completed a research thesis, a Masters and a Fellowship in Lifestyle Medicine, they smirked. How is that going to help anyone in the Emergency Department? The easy answer is it won’t. The real answer is that the vast majority of medicine is never delivered in the emergency department. It is delivered in your clinic, in the everyday family medical centres and specialist practices doing their quiet, unglamourous best to keep people out of hospital. And the chronic diseases that fill our EDs? Many of them are the acute exacerbations of conditions that Lifestyle Medicine exists precisely to prevent or meaningfully reduce.

Lifestyle Medicine is not how many holidays you take per year, nor is it soft wellbeing advice that requires you to follow a hack or protocol never tested against your specific physiology, your own habits, your gender or stage of life. We forget that we are living, biological organisms. We respond to our environment. We have somehow, collectively and rather conveniently, forgotten that we are animals, and that our physical capacity, our cognitive capacity and our emotional resilience, are direct expressions of our environment, our choices and our behaviours. Our Lifestyle. Facing that is uncomfortable. Not just for patients, but for clinicians too. It requires communication and connection skills that appointment structures don’t easily accommodate. It requires patients to develop genuine self-efficacy. It also requires us to accept the possibility that not every answer will be a medication, or another test, and that not every presentation can be named.

The fact that we can’t always provide a name or a diagnosis for a patient is not only deeply unsatisfying for both clinician and patient, it’s a situation where a void is created, a troubling, liminal space where we can easily throw up our hands and feel nothing more can be done. This is not true. This gap is where Lifestyle Medicine excels. Proper, rigorous Lifestyle Medicine is not a collection of wellness trends; it’s very clinical, precise and based on first principles of chemistry, biochemistry, anatomy and physiology. And it’s all encompassing. This specialty has evolved to follow the facts rigorously; we are animals responding to our environment. Nutrition, exercise, sleep, stress and emotional wellbeing, substance use, social connection and the natural environment. These are the six pillars of Lifestyle Medicine.

The mechanistic pathways beneath each pillar exist, but for most of us they are buried- lodged somewhere in a textbook study session or a research article we have not had time to read. Lifestyle Medicine is designed to lift these mechanisms out of the literature and into clinical practice, where they belong.

We are at a defining moment in healthcare, and the destination is visible: a meaningful reduction in our chronic disease burden. The evidence that these pillars lead there is substantial. The harder question is how we do this in real time, with full appointment books and patients already living inside the consequences of a system that has not kept pace with the evidence. This is where many of us are feeling the tension.

The answer is not to revise everything from the beginning. Your education and training already gave you the mechanisms. Revisiting them with the eyes of a clinician, not as a student, means applying them to a specific person, with a specific history, sitting in front of you now. You already have the knowledge. Helping patients this precisely is why we went into health care.

Nutrition

Nutrition’s influence on human biology- and we are, simply, animals responding to our environment- extends well beyond blood glucose monitoring or measuring lipid and cholesterol profiles. That is skimming the surface. Nutrition is where clinical practice has the most to gain from returning to first principles. Nutrition is deep biochemistry. There are thousands of biochemical pathways, physiological responses and genetic switches that are critically reliant on what we expose our cells to through food and beverages.

At the cellular level, dietary methyl donors (including folates (B9), choline, methylcobalamin (B12), methionine, etc) act alongside redox-active compounds and micronutrients (including ascorbates (vitamin C), tocopherols (vitamin E), polyphenols, flavonoids, glutathione, carotenoids, Coenzyme Q10 and selenium). Together, they allow direct modulation of DNA methylation, histone acetylation and chromatin remodelling. In plain terms: what a patient eats or drinks alters which of their genes are expressed, without ever touching the underlying DNA sequence. The implications for patients are real. Largely preventive, but some offer evidence as treatment-grade interventions. Long-term disease risk across specific cancers, cardiovascular disease, and infertility is modifiable when we address global DNA hypomethylation- a state of low methylation, mechanistically linked to genomic instability.

This is nutrigenomics operating in every single consultation, whether you name it that or not.

Our microbiomes (ALL of them, including the gut, respiratory, skin and reproductive tract ecosystems) function as central mediating hubs between our diet and our systemic biology. We are teeming with life we cannot see, that evolved on and in us for a reason, and it responds, poorly or very well, to what we eat and drink. Fermentable fibres and resistant starches drive short-chain fatty acid production within our gut bacteria; butyrate in particular feeds our colonocytes, reinforces tight junction integrity at the gut lining and regulates immune cell differentiation, allowing our white blood cells to complete their maturation into the functional, protective cell lines that defend us correctly. Low-fibre, high-fat eating patterns do the opposite, driving dysbiosis, endotoxin release from unhealthy microbial populations and translocation across cellular barriers to our circulation. Upon their presentation to the immune system, we see the unfortunate consequences of long-term innate immune activation and systemic inflammation.

Immune competence is so heavily nutrition-dependent, its importance cannot be overstated, with implications spanning infectious disease management, cancer surveillance and autoimmune disease. Amino acids, zinc, vitamin A-derived retinoic acid, and the ‘vitamin’ D we synthesise via UVB photon exposure all serve as substrates and signalling molecules within critical immune responses. Both undernutrition and specific micronutrient insufficiencies- especially those that don’t always appear in standard pathology testing- silently impair our host defences.

Redox biology, phytochemicals from plants (which is, at its core, simply pharmacology), and nutrient-sensing pathways (including mTOR, AMPK, G-protein coupled receptor signalling) are not adjunctive considerations that might be relevant. They are operating in every patient you treat, detecting energy availability, adjusting cellular growth, autophagy and lipid handling in real-time, in every consultation, with every patient.

There is more mechanistic detail and clinical elaboration coming- this is my entire focus for Analyse, across the newsletter, the podcast, and the lectures. We will get there together. For now, the clinical opportunity is not to become a nutritional biochemist. It is to ask more precise questions, and to understand that the answers are mechanistically relevant. They are not abstract research constructs. They are alive in your patients.

Part Two is coming next.

The remaining pillars- exercise, sleep, stress and emotional health, substance use, social connection and time in nature, deserve their own detailed attention. Each pillar carries the same mechanistic weight as nutrition. Each one is fully operational in your patients right now, whether or not it appears in a pathology result or if it’s able to be measured at all. Lifestyle Medicine stands to bring these gaps into focus. It targets our inherent biology, which has been operating well before the literature was published, and it just keeps running our body continuously, not waiting to see if we will catch up.

Part Two will be the last issue of Analyse available before the paid tier begins in October. If you are not yet a subscriber, now is a reasonable time. To all current subscribers- thank you. Many of you are past undergrad students, colleagues and fellow practitioners, people who have known and supported my work for close to twenty years. You showed up early. For that reason, you are grandfathered/grandmothered and will always remain a free subscriber, that won’t change. It’s my way of sincerely thanking you for being here from the beginning.

Analyse is written primarily for clinicians- GPs, specialists, Naturopaths, medical and naturopathy students or allied health professionals who suspect the current model isn't giving patients the full picture. Clinical biochemistry and physiology, mechanistic and evidence-based. I write and apply everything to the patients already sitting in your waiting room.

But there is another reader I write for equally. The patient who has done their own research, who walks into appointments with questions their doctor wants to answer, but does not always have time for. They want to understand the mechanisms behind their own health- not just their prescription. I write this for you too. You are equally important as any clinician who reads this.

I want to get this into the hands of as many colleagues, past students, and curious minds as I can before the paid tier begins. If you know someone who should be reading this too, please forward it.

Thank you for reading. I am glad you are here.

Annalies

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