The Dose Makes the Remedy: Hormesis and Your Skin

In the sixteenth century, the Swiss physician Paracelsus wrote a line that pharmacologists still quote: the dose makes the poison. Almost anything can harm in excess, and almost anything can be harmless in a small enough amount. Four centuries later, scientists found that the idea has a second half. Sometimes the right dose of something stressful doesn’t just do no harm. It makes the living thing stronger. That second half has a name: hormesis. And it may explain why retinoids and exfoliants work for your skin, and why too much of them backfires.

What Is Hormesis?

In 1943, two researchers, Chester Southam and John Ehrlich, were testing an extract of Western red cedar heartwood on wood-decaying fungi. At high concentrations, the extract stopped the fungi growing, as expected. At very low concentrations, it did something unexpected: the fungi grew more. They named the effect hormesis, from the Greek hormáein, “to set in motion.” The pattern has since been found across biology, from plants and microbes to animals and human cells. Plotted on a graph, it doesn’t look like a straight line, where more of a stressor always means more damage. It looks like a curve. Too little does nothing. The right amount triggers a protective response that leaves the organism better prepared than before. Past a certain point, the same stress overwhelms those defenses and causes harm. The important word is response. The benefit doesn’t come from the stressor itself. It comes from what the body builds in answer to it.

Hormesis in Everyday Life: Exercise, Heat and Mithridates

You know hormesis even if you’ve never heard the word. Exercise is the clearest example. A hard workout creates small amounts of damage in muscle and a burst of reactive oxygen species, the same molecules usually described as harmful. The body answers by repairing the muscle stronger and increasing its own antioxidant defenses. In a 2009 study led by Michael Ristow, healthy young men who took high doses of vitamins C and E during four weeks of exercise saw fewer of exercise’s benefits. Their insulin sensitivity improved less, and so did their bodies’ own antioxidant defenses. The stress, it seems, was part of the signal. Heat works similarly. Brief exposure prompts cells to make heat shock proteins, which help other proteins keep their shape under stress. There is an older, darker version of the idea too. Legend says that Mithridates VI, king of Pontus, feared assassination so much that he took small doses of poison every day to make himself immune. Whether or not the story is true, the word mithridatism survives, and with it the intuition that a body can be taught to withstand what would otherwise harm it. In every one of these examples, the strengthening happens afterwards, in recovery. The workout is the signal. The rest is when the body answers it.

How Plants Use Stress, and What Skin Can Learn

Plants can’t run from a drought, a frost or a burning sun, so they’ve become masters of the stress response. When challenged, many produce protective compounds: antioxidants, pigments and molecules that help their cells hold water and keep their structure. Some scientists think part of the benefit of eating plants comes from these compounds, signals of stress passed from one organism to another. The plants that grow in the harshest places are often the most practiced at this. In LAMELLARE™, we use a cell culture of the blue globe daisy, Globularia cordifolia, a small alpine plant that clings to bare limestone high in the mountains. Its cell culture is studied for a hormetic effect: helping skin activate its own defense and renewal processes, so it looks more radiant, even and resilient. It’s the same principle as exercise, applied at the scale of a single ingredient: don’t do the work for the skin, prompt the skin to do it better itself.

Hormesis and Skin: Retinoids, Exfoliants and the Curve

Hormesis also explains something that anyone who has used a retinoid or an exfoliating acid already knows. These are, in a sense, controlled challenges. An exfoliant loosens the bonds between surface cells so they shed faster. A retinoid speeds up renewal. Used well, skin responds: texture smooths, tone evens, and over weeks the skin becomes more comfortable with the treatment. Dermatologists sometimes call the first phase the “retinization period,” the few weeks in which skin adjusts before it settles. Used too much, too often or without a break, the same treatments push skin past the top of the curve. The barrier, already thinner in dry and mature skin, can’t keep up. Dryness, stinging and redness follow: the classic signs of retinoid irritation and over-exfoliation. More intervention, past a point, is not better intervention. But the bottom of the curve matters too. A treatment too weak to prompt a response does very little, however gently it’s used. That’s why we make our formulas potent, at concentrations informed by research, and let the rhythm of use, not a weaker formula, set the dose. High potency, measured rhythm. The most important variable, then, is often not what you use, but how much and how often, and what happens in between.

Rest Nights: The Layland Method™

The rest is where the answer comes. This is the thinking behind The Layland Method™, our signature protocol. It takes its name from the fallow field, the land left unplanted for a season so the soil can recover and return richer.

Like skin cycling, the Method alternates treatment nights with recovery nights. But it’s built around hormesis: a potent challenge, then the materials and time skin needs to answer it. The Method treats skin the way good training treats the body:

• On chosen evenings, a measured challenge: LISSE™ for gentle exfoliation, or RÉAU™ for retinoid care. Never both on the same night. Start with one to three nights a week.

• On the evenings in between, recovery: BUFFÈRE™ and LAMELLARE™, with lipids, ceramides, humectants and peptides that give the barrier the materials it needs.

• On the driest evenings, a seal: BASTINA™ helps reduce moisture loss overnight, when skin is busiest repairing itself. Layer it over LAMELLARE™ once your skin is comfortable with its treatments. Sealing layers do more than sit on the surface: in a 1992 study, petrolatum helped a damaged skin barrier recover faster.

Rest nights are not “off” nights. They are when the skin answers the challenge. Leave them out, and you have stress without adaptation. Keep them, and the same treatment can do more good with less harm.

The Layland Method™ is our signature skin protocol for very dry, sensitive and aging skin. It pairs high-potency treatments with deliberate rest, and each formula is made in small batches, au bain-marie.

 

How to Use Actives Without Damaging Your Barrier

• Start low. Begin a new active once or twice a week and increase only as your skin stays comfortable.

• Change one thing at a time, so you can tell what your skin is responding to.

• Watch for the edge of the curve. Stinging, tightness that lasts, flaking or redness are signs to pull back, not push through.

• Protect the recovery. Replenish the barrier on rest nights, and wear sunscreen every day: renewing skin is more vulnerable to the sun.

• Remember that more is not better. The goal isn’t the strongest possible routine. It’s the right dose, at the right moment, with time to respond.

Paracelsus was right that the dose makes the poison. But hormesis suggests he was only half right, because the dose also makes the remedy.

Frequently Asked Questions

What is hormesis? Hormesis is a biological response in which a low dose of a stressor triggers protective effects that leave the body stronger, while a high dose of the same stressor causes harm.

Is skin cycling the same as hormesis? Skin cycling uses the same idea. A challenge night, with a retinoid or exfoliant, is followed by recovery nights so skin can adapt instead of becoming irritated.

How often should I use a retinoid? Start with one to three nights a week and increase only while skin stays comfortable. Expect a few weeks of adjustment, sometimes called the retinization period.

Can I use exfoliating acids and retinoids together? Use them on separate nights, not together. Combining them on the same night makes irritation much more likely.

What are the signs of over-exfoliation? Stinging, tightness that lasts, flaking and redness. If you notice them, pull back and focus on barrier repair until your skin settles.

Sources

• Southam CM, Ehrlich J. Effects of extract of western red-cedar heartwood on certain wood-decaying fungi in culture. Phytopathology, 1943;33:517–24. (Background: BMJ, “When I use a word… Hormesis”)

• Calabrese EJ, Baldwin LA. Hormesis: the dose-response revolution. Annual Review of Pharmacology and Toxicology, 2003;43:175–197.

• Ristow M et al. Antioxidants prevent health-promoting effects of physical exercise in humans. PNAS, 2009;106(21):8665–70. (PMC)

• Ghadially R, Halkier-Sorensen L, Elias PM. Effects of petrolatum on stratum corneum structure and function. J Am Acad Dermatol, 1992. (PubMed)

• Sederma (Croda). Use of an extract of Globularia obtained by in vitro plant culture. (US9925135)