Hormesis - What It Is, When It's Unsafe, and Some Common Practices to Consider
Hello, I am Julie Donaldson and I am a clinical nutritionist with functional health training. I specialize in restoring balance in complex, chronic and acute health conditions. I welcome you to peruse other articles that may be of interest to you in your health investigation!
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Fasting, goldenseal, high intensity interval training and cold plunges plus hot therapies all have beneficial effects on the body, and that is one thing they have in common. But here, we are discussing another thing they have in common which is the fact that they are hormetic stressors. What exactly is a hormetic stressor? It is most definitely something to be used in your holistic health regimen, but it has limitations…let’s dive in and cover the facts as well as the warning signs of too much hormesis.
What is hormesis?
Hormesis and cold water
Do you know the feeling of being doused with (or plunging into) cold water? This stimulates hormesis. The practice of cold plunging has long been used across Europe and Scandinavia. Following a hot sauna or steam bath, a cold plunge into water or snow is a common practice and is used for the purpose of creating hormesis. Many people avoid exposure to cold this way due to its extreme feeling! Of course, prolonged exposure would be very stressful. But, used in moderation, it is very good for the body…discomfort actually happens in your brain, not on your cold skin or tired legs. Training your brain to withstand stressors strengthens your adaptive stress response.
Generally speaking, hormesis provides a temporary and unique stress response that initiates change. It is a a process in which exposure to a low dose of a chemical agent or environmental factor that is damaging at higher doses induces an adaptive beneficial effect on the cell or organism.
Hormesis In toxicology is a “dose response phenomenon” to xenobiotics or other stressors characterized by a low-dose stimulation, with zero dose and high-dose inhibition.
In physiology and nutrition, hormesis can be visualized as a curve with regions of deficiency, homeostasis, and toxicity. Physiological concentrations deviating above or below homeostasis concentrations adversely affects an organism with an ensuing shift in physiology. We talk a lot about homeostasis at True Nature and the fact that Metabolic Typing® helps us to attain and maintain homeostasis. Hormesis actually disrupts homeostasis, but also broadens its territory and includes its re-stabilization (when used properly). A disruption of homeostasis leading to the activation of one or more stress responses (SR) to counteract the disruption is the fundamental molecular basis of hormesis. Starting from the exposure to a stressor to the potential occurrence of physiological hormesis, the SR process may be understood via the following steps: (1) stress-induced disturbance in the homeodynamic equilibrium; (2) activation of signaling pathways to initiate SR pathways; (3) activation of SR pathway-mediated effector responses; and (4) restoration of homeodynamics and eventual enhanced adaptive ability . It is important to note that the molecular and physiological responses initiated by SR are not strictly limited to match the level of disruption, and almost always lead to modest overcompensation.
The burst of oxidative stress generated by hormesis induces a signaling pathway involving the transcription factor Nrf2. (Transcription factors are proteins that bind to DNA to activate genes.) The presence of free radicals generated in oxidative stress prevents Nrf2 proteins from breaking down as quickly. This means more Nrf2 can travel into the nucleus of cells, where it binds to DNA and triggers the production of powerful antioxidant enzymes such as glutathione and phase II detoxification enzymes. Nrf2 regulates the expression of phase II detoxifying enzymes and antioxidants in response to noxious stimuli.
This chart displays the critical pathways that are affected by Nrf2 and involve the breaking down and detoxification of chemicals/petrochemicals, hormones, plastics, heavy metals (and other non water soluble molecules). These pathways are investigated and addressed in True Nature processes on a regular basis, and it is important to note that stressing these pathways without providing cofactors and adequate support can produce negative responses:
Nrf-2 affects phase II detoxification
These enzymes make the body more efficient at neutralizing toxins and high levels of oxidative stress. So, oddly enough, by triggering a little oxidative stress now, hormetic stressors can help you neutralize more oxidative stress later.
Akin to any other type of stressor, hormesis is not effective for long-term application. Also, the quantification of “low dose” is extremely difficult because of the inter-individual variability in sensitivity. Indeed, fragile subjects (e.g, elderly, chronically ill, children, fetuses) having poor inducibility of their defense mechanisms activated by hormesis, can experience harm to their health by lower exposure doses tolerated by other subjects. Hormesis is a toxicological event, and thus is ultimately likely to derail homeostasis if used on a prolonged basis.
Also, while hormesis is most often thought of in the context of exposures to exogenous agents or environmental conditions, it should also be recognized that hormesis is integral to the normal physiological function of cells and organisms. For example, exposure of neurons to the excitatory neurotransmitter glutamate during their normal activity results in energetic and oxidative stress accompanied by activation of hormetic pathways that help the neurons cope with more severe stress. However, excessive activation of glutamate receptors can kill neurons in a process called excitotoxicity.
Let’s talk about some other things in this category that many people are over-using because their effects are less immediately noticed…
Fasting is possibly the #1 misused hormetic stressor
I’ve written about healing and fasting, discussing the benefits and potential harms of intermittent fasting, which is currently the most popular form of fasting. The emergence of any positive research results around intermittent fasting (such as weight loss or blood sugar regulation) has led to the belief that it is a practice that should be used regularly. If one is lucky enough to experience those positive benefits, the desire and motivation to utilize it daily become high. Like with many dietary shifts (including ones like Keto & carnivore), there is often an initial positive response and this tends to reinforce the idea that it is beneficial for the long-term. But this is not the case. Long-term use actually halts many of the positive pathway responses that occur initially with intermittent fasting. Remember, intermittent fasting is hormetic and hormesis is a toxicological event - sustained use of intermittent fasting can produce multiple stress responses and toxic effects in the body.
Goldenseal is both powerfully healing and powerfully hormetic
Goldenseal
While the benefits of goldenseal are numerous and quite potent, many people are not aware of its powerful hormetic properties. I have worked with a lot of clients who use it all winter long (often in combination with echinacea) to “prevent” or treat colds and flus - this becomes like long-term fasting, defeating the therapeutic value of the substance and creating health risks.
Its benefits include those of being anti-cancer, cardioprotective, anti-viral and anti-parasitic. On the other hand, its very high berberine and berberrubine content produce hormetic responses and can, with long-term use, cause liver cancer, changes in spleen cell structure and disrupt DNA processes. Goldenseal should only be used for about 3 weeks at a time.
Milk thistle is not traditionally labeled as a hormetic stressor, but let’s talk more about this
Milk thistle
Milk thistle is an incredible offering from Mother Nature. Its benefits include the following:
Liver protection and free radical reduction
With this wide range of exceptional beneficial effects, milk thistle has become one of the most commonly used supplements in the natural medicine world. It is certainly used here at True Nature in many circumstances. But, what is “up for grabs” with milk thistle is the possibility that it is a hormetic stressor. Studies on the herb have been criticized for being “heterogeneous and contradictory”, often based upon specific supplements and not conducted on humans with rigorous guidelines. Perhaps the most important statement made by researchers is this: “As biological studies progress, it remains important to make the distinction between silymarin and silybin and their respective and distinct compositions”. Silybin is the major active constituent in silymarin, the compound in milk thistle that is most frequently researched. Silybin is high in phenolic compounds and phenolics are known to produce hormetins.
We do know that milk thistle stimulates the liver - and we know that it speeds up the production of phase II liver enzymes. While these are potentially beneficial responses, again, too much of a good thing can become a bad thing. We also know that there are potential risks for estrogen-linked disease progression and excess lowering of insulin with long-term milk thistle use. A very general consensus in the field of research is that we need a lot more controlled studies on milk thistle.
For all of these reasons, I tend to put milk thistle in the category of hormetic stressors in my practice. Over the course of decades, I see better results when its use is limited vs. continual. While this is primarily empirical observation (vs. testable), symptom expression and blood chemistry do reveal information that is useful in making these choices. (Note: almost any herb or natural medicine, as well as many foods, could potentially fall into this category - most of them “push” the physical body. For this reason, it is best to use the professional guidance of a trained coach to create the proper individual dose and rhythm of use of any substance for healing.)
Some signs/symptoms that you could be over-doing hormesis
Here are some of the most typical responses in the body when hormesis has turned from helpful to harmful:
food sensitivities and/or digestive stress
insomnia and/or “tired but wired”
agitation/over-stimulated nervous system
poor detox responses
homeostatic dysregulation, especially blood sugar, blood pressure and body temperature
racing heart
headaches
muscle and/or joint pains, jaw clenching
weak immune responses
Summations and solutions for hormetic practices
Hormesis can provide a supportive element in your healing program, but only in the right forms and frequencies. Let’s look at a list of practices ranging from the subtle to more intense.
We all know that too much sun exposure is a bad thing - but studies show that the stress of UV radiation, in the right dose, prevents cancer.
Homeopathy is a healing approach that utilizes micro doses of toxic substances in many circumstances. With the understanding of “like cures like”, a tiny dose of an offensive substance can awaken these pathways and stress responses in the body just enough to create change through an adaptive response..
Breathing techniques that include sustained holding of the breath are considered to be hormetic stressors. Oxygen deprivation produces a specific hormetin.
Heat (sauna) therapy has been shown to be beneficial to all forms/stages of neurodevelopment and anti-aging. That being said, no one can stay in a sauna continuously! Its benefits are driven by heat-shock proteins (hormetins).
Intermittent fasting can absolutely help some people in some conditions with a boost to their healing. For others, it can negatively impact hormonal levels and increase cardiovascular risks. It is never appropriate as a continual practice.
High intensity interval training (HIIT) is also researched to provide the beneficial effects of hormesis. During these intense workouts, your muscles are briefly starved for oxygen, creating hypoxia, which stimulates the production of mitochondria. You're also activating fast-twitch muscles, which may support longevity. Again, too much of a good thing is fairly clear to most people who are regular exercisers and have tried HIIT - mitochondrial boosting turns into exhaustion and inability to recover and exert.
These practices graduate from the subtle to the more intense. Always, consult with a professional before including more intense practices in your regimen - there may be individual health circumstances that create warning for such practices. At True Nature Health Consulting, we are committed to personalizing your approach to your health, beginning with nutrition that stabilizes your healing. We offer holistic telehealth services. Please write to me at Julie@truenaturehealthconsulting.com for more information.