The "Right Kind of Poison" Strengthens the Body: The Science of Hormesis

Two thousand years ago, there was a king. Fearing assassination from a young age, this king drank small amounts of poison every day. Arsenic and various other toxins. Little by little, he introduced them into his body.

Mithridates VI of the Kingdom of Pontus. The man who ruled what is now Turkey.

As a result, he acquired resistance to all kinds of poisons. Later, when he was defeated by the Roman Empire and tried to commit suicide, he could not die even after drinking poison. The resistance he had built up was too strong.

I want you to remember this story. It is directly linked to the essence of "strength training" and "health."

This time, I will talk about "Hormesis." It is the principle that small amounts of stress strengthen the body, and everything from strength training and fasting to the health benefits of vegetables can be explained by this.

Philosophers and doctors are saying the same thing.

A famous passage from Nietzsche: "That which does not kill me, makes me stronger."

You often see it in collections of quotes, and I always thought it was just poetry. But it's not. This is a biological fact.

The 16th-century physician Paracelsus, known as the father of modern toxicology, said this:

"All things are poison, and nothing is without poison. The dosage alone determines that it is not a poison."

Even water will kill you if you drink too much. Even oxygen becomes a poison if it is too concentrated. It is not the substance that determines whether it is a poison or a medicine. It is the amount.

However, that "small amount of poison" actually strengthens the body. As a doctor, it was hard to accept. The premise is "avoid harm," so what do you mean harm strengthens the body? But the more I researched it, the more correct it was.

What is Hormesis?

A phenomenon where small amounts of stress actually enhance biological functions. It is easy to understand if you put it on a graph.

If stress is zero, the body weakens. If it is excessive, it breaks down. Only the "just right amount of poison" trains the body. It is an inverted U-shape.

Mithridates proved this with his own body 2,000 years ago. And "that thing" you always do is also hormesis itself.

Yes, strength training.

Strength training is the "right kind of poison" (Hormesis and muscle hypertrophy).

What strength training does is destroy muscle fibers.

Every time you lift a barbell, micro-damage occurs in the muscles. Inflammation occurs. Pain occurs. From a microscopic perspective, it is completely "harmful."

But the body adapts to that harm. It repairs itself slightly stronger than it was before it was damaged. This is supercompensation.

Strength training is planned destruction. It is hormesis itself.

In my 17 years of training, the moment I felt this most acutely was when my bench press stalled at 120kg for three months. I went to the bench every day, changed my form, added accessory exercises, and still didn't gain a single kilogram.

A training partner who couldn't watch me struggle anymore told me, 'Stop benching for a week.' Honestly, I didn't want to. I thought if I rested, I would lose progress.

A week later, the bar felt impossibly light when I gripped it, and I lifted 130kg. 'Just breaking it down isn't enough; you have to let it recover to get stronger.' I finally understood this obvious truth with my own body.

I knew the theory. As a doctor, I had read about supercompensation in textbooks. But 'knowing' and 'understanding' are two completely different things.

Fasting, Cold Water, Blood Donation: Getting Stronger by 'Losing' Things

It's not just strength training. Hormesis is everywhere in daily life.

Fasting

I keep my daily eating window to about 12 hours and finish dinner early. The amount I eat decreases naturally, and my digestive system gets a long rest. I used to push it down to an 8-hour window, but I overdid it, my training recovery dropped, and I started waking up at 3 a.m. Now, I've gone back to a looser schedule and just incorporate longer fasts occasionally, which feels just right. The full process of returning to an appropriate amount from there is written in The story of why I quit the 16-hour fasting I was obsessed with.

Cold Water Immersion

When you submerge yourself in cold water, norepinephrine levels spike. It is a substance that governs focus and alertness. Your head clears, and your mood lifts. The feeling of being 'refreshed' in a cold bath after a sauna is based on a similar principle.

'Saunas are good for the body' vs. 'No, they're bad for the heart.' This couldn't be settled by hormesis alone. Observational studies and intervention trials confirm different things. I wrote about what I found when I re-researched this in The story of a doctor who got hooked on saunas and started skipping the gym (members only).

Japan's 'cold weather training' (kangeiko) wasn't just about willpower, either. It was hormesis.

The next one, blood donation, is my personal favorite.

Blood Donation

Drawing blood. At first glance, it seems bad for the body. But the body tries to compensate for the lost blood by producing a large amount of new red blood cells.

And that's not all.

The male body has almost no mechanism for excreting iron. Women lose iron every month through menstruation, but men do not. Accumulated iron increases oxidative stress.

For men, blood donation is one of the few ways to 'remove iron'.

From Hippocrates to the Middle Ages, doctors used 'bloodletting' as a treatment. Modern medicine dismissed this as 'superstition.' However, observational studies have produced data suggesting that people who donate blood regularly tend to have a lower risk of cardiovascular disease⁵⁾. While we are not at the stage where we can definitively state causality, it cannot be ignored.

The benefits of blood donation are not just about 'removing iron.' When plasma is removed during component donation, old proteins are also removed, prompting the liver to synthesize new ones.

Currently, 'Therapeutic Plasma Exchange' is trending among longevity enthusiasts in Silicon Valley. The idea is to replace old plasma with young plasma to dilute aging factors, costing several million yen per session. However, this is not the same as blood donation. The core of plasma exchange is the process of 'introducing' young plasma, which is its selling point. Blood donation is only about 'removing'.

Even so, the part about 'removing old things and forcing the body to rebuild' happens for free at blood donation centers near train stations. I believe that alone makes it worth going.

However, doing it too much leads to iron deficiency, which is counterproductive. Anemia, fatigue, and decreased concentration. The moment the 'right kind of poison' turns into 'just poison.' Blood donation is also not immune to the inverted U-curve.

I also go to donate blood twice a year. After removing 400ml, I have a sensation that my body feels lighter.

My ferritin (iron storage) levels have dropped from 330 three years ago to 102 through regular blood donation. Why does the male body lack a 'function to discard iron,' how should one interpret ferritin levels in health checkups, and at what pace should one remove it? I have summarized the entire process in Blood Donation is Medical Maintenance (members only).

The relationship between why vegetables are healthy and hormesis

Why vegetables are good for the body. Many people think it is thanks to vitamins and dietary fiber. Half of that is correct. But the other half is wrong.

Sulforaphane in broccoli, polyphenols in blueberries. Those are 'defensive toxins' that plants create to protect themselves from insects and fungi.

Plants cannot run away. Even if they are eaten, they cannot move from that spot. That is why they arm themselves with chemical substances. That bitterness and astringency are their weapons.

When humans eat them, the body recognizes that 'a trace amount of poison has entered,' activates the detoxification and antioxidant system (Nrf2 pathway), and produces a large amount of antioxidants. As a result, you become healthier.

Once you understand this mechanism, you can also understand why the body's reaction differs between 'supplements that only extract vitamin C' and 'whole broccoli.' Supplements only deliver nutrients. Vegetables come with 'a small amount of poison' attached to the nutrients. It is the latter that flips the switch.

There are several reports stating that taking vitamins alone does not have much of a life-extending effect. This is likely the reason.

The reason wasabi is good for the body and chili peppers boost metabolism follows the same principle. That is not 'spiciness,' but 'a trace amount of poison'.

In other words, vegetables are healthy not just because of the nutrients. It is because they are 'slightly poisonous'.

Poison, muscle training, hunger, cold, and vegetables. The same principle exists right at your dining table.

The 'zero-stress faith' that business leaders fall into and the inverted U-curve of hormesis

When working as a personal doctor, I often encounter a certain pattern. It is the business leader who tries to eliminate all stress.

Top-tier bedding. Perfect climate control. Low-irritant meals. Perfectly managed nutrition through supplements. Aiming for "zero stress" at all costs.

I understand the sentiment. You are covered in stress at work every day, so you want at least your private life to be comfortable.

However, a zero-stress environment weakens the body.

NASA astronaut research demonstrates this. In zero gravity (where the load on bones and muscles is almost zero), bone density decreases by 1% to 1.5% per month. Muscles also atrophy rapidly.

The body degenerates without stress.

Conversely, the bones of people who continuously apply load through squats and deadlifts are as strong as steel beams. The astronaut whose bones dissolve and the lifter whose bones grow stronger are two sides of the same principle.

Comfort quietly kills the body.

When I told this to a business executive, they asked, "So, if I skip leg day, is the same thing happening to me as an astronaut?" Yes. The scale is different, but the principle is the same.

Plants grown in a greenhouse wither when taken outside. Plants exposed to the wind develop stronger roots. Humans are the same.

Here, those who read the previous The 'Subtractive Health' a Doctor Realized After 17 Years might have thought, "Hmm?" In that article, I wrote that you should first subtract ultra-processed foods, nightcaps, and smartphones before bed.

There, I said "subtract," and now I am saying "introduce poison." It looks like a contradiction. But it is not. Via Negativa is "subtract unnecessary harm," while hormesis is "introduce the right kind of harm."

There is an order to it. First, subtract the unnecessary things. Convenience store bento boxes, nightcaps, late-night smartphone use. On top of that, introduce the right kind of stress. Strength training, fasting, cold water.

Subtract first, then add. If you do it in reverse, everything will break. You cannot fill a bucket with holes in it by pouring water into it. First, plug the holes.

The order of health is subtraction first.

Three conditions that distinguish "the right kind of poison" from "just poison"

Hormesis is not a panacea. If you overinterpret "stress is good for the body," it can become dangerous.

Chronic sleep deprivation is not "the right kind of poison." It is just poison. Overtraining seven days a week and heavy daily drinking are also just poison.

There are three conditions for "the right kind of poison." It must be temporary. There must be time for recovery. You must be able to control it yourself.

Strength training ends in an hour and recovers in 48 hours. Fasting ends in 16 hours and you eat again. Cold water immersion ends in a few minutes and you warm up. Everything has a beginning and an end.

Stress without an end is nothing but poison.

I made this mistake in my 30s, too. Thinking that 'the harder I push, the stronger I'll get,' I trained six days a week, cut back on sleep, and packed my work schedule to the limit.

As a result, my immune system crashed and I nearly developed pneumonia. A respiratory specialist getting pneumonia—it’s not funny. That wasn't hormesis; it was just overkill.

Let's revisit Paracelsus: 'The dose makes the poison.' Too much, and it’s just poison. And the tricky part is 'stacking too much'.

Fasting, strength training, and cold plunges are each a 'right kind of poison' on their own. But doing a 24-hour fast, pushing yourself with HIIT, and then jumping straight into an ice bath? That’s a simultaneous terrorist attack of toxins.

This is especially common among obsessive entrepreneurs. Because they are stoic, they try to do everything. When I check their blood work, their stress hormone levels are off the charts.

What matters isn't the number of techniques. Once you understand the principle that 'the right amount of poison strengthens the body,' you can decide for yourself what to do and how much to do.

Signs that recovery isn't keeping up

A checklist to see if you're okay.

• You still feel tired after sleeping for three or more consecutive days.

• Your training weights haven't increased for over two weeks (or have actually decreased).

• You are catching colds more frequently.

• You lack motivation. Everything feels like a chore.

If even one of these applies to you, your recovery isn't keeping up. It’s a sign that the 'right kind of poison' has turned into 'just poison.' First, rest.

Hormesis List: The Boundary Between 'Right Poison' and 'Just Poison'

I’ve summarized the hormesis methods mentioned in this article for your reference, including their benefits and what happens when you overdo them.

Strength Training

• Right amount: Muscle hypertrophy, improved bone density, better insulin sensitivity, mental stability.

• Overdoing it: Rhabdomyolysis, joint injury, chronic inflammation, weakened immunity.

• Guideline: 3-4 times a week, within 60 minutes per session. Allow 48 hours for recovery.

After I reduced my training from six days a week to four, my muscle mass clearly increased. The 'days off' are what build the body.

Fasting (Intermittent Fasting)

• Optimal amount: Improved insulin sensitivity, reduced body fat, suppression of late-night snacking

• Excessive amount: Muscle breakdown, hypoglycemia, hormonal abnormalities, rebound overeating

• Guideline: 16 to 24 hours, once to several times a week. Avoid prolonged daily fasting.

Cold Water Immersion/Sauna

• Optimal amount: Increased norepinephrine, alertness/mood switching, stress reduction

• Excessive amount: Risk of arrhythmia, hypothermia, excessive strain on the heart

• Guideline: Cold water for within a few minutes. Start with 1 to 2 sets of cold baths after the sauna.

At first, I would jump out in 10 seconds. Now, I'm fine for a minute. I can feel my body adapting for myself. This, too, is hormesis.

Blood Donation

• Optimal amount: Excretion of excess iron (reduced oxidative stress), removal of aging proteins

• Excessive amount: Iron-deficiency anemia, fatigue, decreased concentration

• Guideline: Whole blood donation 2 to 3 times a year (follow the standards of the blood donation center).

The day after donating 400ml, my body feels strangely light. Thinking that new blood is being made to replace what was taken makes me feel like I've gained something.

Defensive Toxins in Vegetables

• Optimal amount: Activation of the Nrf2 pathway, triggering detoxification and antioxidant systems, reduced risk of chronic disease

• Excessive amount: Large doses via supplements carry a risk of liver and kidney damage (eating vegetables is generally not a problem).

• Guideline: Eat vegetables as they are. Avoid large doses of single-component supplements.

What they all have in common is an inverted U-shape. Zero makes you weak. An optimal amount makes you strong. Excess destroys you.

It's not about "what you do," but "how much you do." What Paracelsus said 500 years ago remains true today.

Finally, what you have in common with Mithridates

After 17 years of training, the biggest change in my body came when I realized that "training is hormesis." I stopped pushing myself recklessly. I became conscious of the cycle of "breaking down" and "recovering." I reduced my schedule from 6 days a week to 4.

When I pulled back, I got stronger.

If you coddle your body, it gets weak. If you break it too much, it breaks. If you "break it correctly," it gets stronger.
Kings 2,000 years ago, doctors 500 years ago, and martial artists standing under freezing waterfalls all knew this. Every time you grip a barbell at the gym, you are doing the same thing.

Summary

• Hormesis = The inverted U-shaped principle where small amounts of stress make the body stronger

• Strength training, fasting, cold water, blood donation, and the defensive toxins in vegetables all work on the same mechanism

• The 3 conditions for the "right kind of poison": temporary, allows for recovery time, and is self-controllable

• Doing all "healthy things" at once is a simultaneous terrorist attack of toxins. Be careful not to overdo it

• The order is "subtract first, then add." Via Negativa comes first, hormesis comes later

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For those who want to know more deeply (Related Articles)

These two articles break down "breaking it correctly" into actual menus and eating habits. How to determine the volume of strength training and the pitfalls of antioxidant supplements.

▼ How hard to push yourself and how many sets to do per week
You didn't need to push to failure or use the hypertrophy range | Explanation of the latest US strength training guidelines

This is the content behind the "I reduced from 6 days to 4 and gained muscle mass" mentioned in this article. Based on the guidelines revised by the ACSM for the first time in 17 years (a review of 137 papers and over 30,000 people), I broke down the facts: you don't need to push to failure, you don't need to obsess over the 8-12 "hypertrophy range," and what works is a total volume of 10 sets per muscle group per week. This is how to determine the amount of training to grow without breaking yourself too much.

▼ Antioxidant supplements alone crush hormesis
The more Vitamin C you take, the more the effects of strength training disappear
This is the flip side of the "vegetables = nutrients + small amount of poison" mentioned in this article. Taking high doses of Vitamin C and E immediately after training can extinguish the reactive oxygen species produced by exercise—in other words, the very switch for adaptation that makes the body stronger. Here, too, hormesis and via negativa (subtracting) are effective. I summarized how to draw the line: get antioxidants from food, and only use supplements when it really counts.

Announcement of the membership "Dr. Mosari Lab"
I run a membership called "Dr. Mosari Lab."
I write about how I implement the "breaking it correctly" method described in this article in my actual outpatient practice and on my own body. What to stop before adding anything, and how to read lab results. I write about things that go a step deeper than what I can put out on X or free notes.

• Content I actually discuss in outpatient visits as a primary care physician for business executives

• Records of what worked and what didn't, tested on my own body while reading research papers

• How to read lab results and how to choose supplements and medications

• Member-only Q&A board

You can read all articles for 1,000 yen per month. You can cancel immediately if it's not for you. If you are interested, please take a look.

*This article is intended for general health and medical information purposes only and does not provide diagnosis, treatment, or medical advice for any specific individual. If you have health concerns, please be sure to consult a medical institution. Fasting and cold water immersion can be dangerous for those with underlying medical conditions. Always consult your primary care physician. For blood donation, please follow the criteria of each blood donation center. The author assumes no responsibility for the consequences of actions taken based on the information in this article.

References: 1) Calabrese EJ, Baldwin LA. Defining hormesis. Human & Experimental Toxicology. 2002;21(2):91-97. DOI: 10.1191/0960327102ht217oa / PMID: 12102503

2) Mattson MP. Hormesis defined. Ageing Research Reviews. 2008;7(1):1-7. DOI: 10.1016/j.arr.2007.08.007 / PMID: 18162444

3) Vaiserman AM. Hormesis, adaptive epigenetic reorganization, and implications for human health and longevity. Dose-Response. 2010;8(1):16-21. DOI: 10.2203/dose-response.09-014.Vaiserman / PMID: 20221294

4) Šrámek P, et al. Human physiological responses to immersion into water of different temperatures. European Journal of Applied Physiology. 2000;81(5):436-442. DOI: 10.1007/s004210050065 / PMID: 10751106

5) Salonen JT, et al. Donation of blood is associated with reduced risk of myocardial infarction. The Kuopio Ischaemic Heart Disease Risk Factor Study. American Journal of Epidemiology. 1998;148(5):445-451. DOI: 10.1093/oxfordjournals.aje.a009669 / PMID: 9737556

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