Hormesis Informs Lithia Works

What is Hormesis?

Around 1796, physicians and researchers in Europe began experimenting with differing doses of substances to see what might or not be a safe yet effective dose, essentially trying to establish, through experimentation, a dose response curve that best reflected observed reality. Surprisingly, about 90 years later, their findings were codified into a very simple concept, named the Arndt-Schultz law. These findings could be described in one short sentence: “For every substance, small doses stimulate, moderate doses inhibit, large doses kill.” This law was based on observations of many hundreds of pharmacological agents, was considered basic science, was taught to every pharmacist and was included in books of pharmacy fundamentals. In more modern terms, this observation described a biphasic response to stimuli, dependent on dose or exposure.

Over the decades, the initial rule disappeared, replaced by dose-responses described as occurring in a linear fashion from low-dose to high. In other words, a low dose of a substance produces a certain effect, and as you increase the dose, the effect increases, essentially forming a straight ascending line. This despite the fact that in many pharmacological clinical trials that occur today, we find either a U shaped or upside down U shaped dose response curve. Indeed, Fluoxetine, or Prozac, the most popular drug made, fits this non-linear response curve. The problem is that the description of a purely linear dose response curve does not well match the full experimental findings.

In the past couple of decades, the person most influential with the desire to describe reality in all its messy clarity is Edward Calabrese, PhD, a professor of Toxicology at University of Massachusetts School of Public Health and Health Sciences, having published numerous books, and over 600 scholarly articles. He was awarded the Marie Curie Prize in 2009 for his work on this biphasic dose response curve, hormesis.

What started him on this path? While conducting an experiment using PHOSFON, a synthetic growth inhibitor on peppermint plants, it was observed that some plant growth was instead stimulated by 40%, the opposite of what was expected. Surprising to everyone, including a young Edward Calabrese, the group had made a dilutional error by a factor of 10. Their experimental finding, using this accidental very low dose of the growth inhibitor, was that plants grew more than expected. At the higher doses of the growth inhibitor, indeed the plant growth was stunted, as predicted. Low dose stimulated whereas high doses inhibited; a biphasic response based on the dilution or concentration of the plant inhibitor was observed.

In his words, after many experiments testing this observation,

 “Regardless of the model (i.e., in vitro or in vivo), inducing agent, endpoint, or receptor/cell signaling pathway mediated mechanism, the quantitative features of the hormetic dose/concentration responses are similar, suggesting that the magnitude of the response is a measure of biological plasticity, within a broad range of biological contexts. These findings represent an important advance in the understanding of the hormetic dose/concentration response, its generalizability and potential biomedical applications, including drug discovery/efficacy assessment and the risk assessment process.”

Hormesis has, at the very basic level two interlocking observations. First, that substances, or stressors, have a biphasic effect, or that subjects/patients have a biphasic response to most stressors. Second, that the lower doses tend to stimulate and the higher doses tend to depress bodily functions. Meaning that instead of a straight dose response curve, we actually find a curvilinear one. For us, the easiest way to explain the contradictory image of what we consider a normal dose response curve and one that includes hormesis is that if you were to measure a dose response curve from ultra-low to very high, one would observe this curvilinear dose response. However, in the current trial design, we tend to look for a certain effect, at more or less a certain dose, and therefore we are not looking at the very ends of the dose response effects. We are looking at the middle parts, and at those parts, the dose response curve is more straight, more as one would expect.

However, that normal straight ascending line looks very neat because we are artificially looking at just part of the response curve. If one were to extend that dosage patterns to the utra-low and ultra-high range, this hormetic response is readily observed. Hormetic responses have been noted for many thousands of substances.

One very clear example of this can be found with lithium. While the current regimen of lithium carbonate use for the treatment of manic depression has been, by and large, miraculous, it does come at a price. For some, the thyroid and the kidneys have known damage by long term use of lithium carbonate, presenting one of the limitations of the drug, and narrowing its therapeutic window. In fact, thyroid disease and kidney disease are two contraindications to its use. This is very well known to every prescribing psychiatrist. Less known is the growing body of evidence that show a potential benefit of low dose lithium or short courses of lithium as kidney protective. Still early in trials, what seems to be developing is a consensus that the GSK3b is modified by lithium and this protects the kidney from damage. You can read about the emerging trials here. The main point I want to make is that while ‘we all know’ that lithium carbonate hurts the kidney in high doses, at the lower dose and for shorter duration, the results may be unexpectedly opposite to it; reflecting a hormetic effect. 

Lithia Works™ leverages the concept of hormetic response to low dose and ultra-low dose stimuli in formulating our products. 

August 18, 2021

Dear folks,

Sadly, we announce that we stopped production, marketing, distribution or sales of Lithia Basic today. This very difficult decision was arrived at in a carefully deliberative manner. We love this product, and know many of you do, too.

As you know, we spent years developing a product that we thought would be applicable for a variety of uses to help normal functioning of different bodily systems, most especially the nervous system/brain and the immune system. We are pretty proud of what we achieved there. However, it had to stop. The reason follows.

We are in the midst of the COVID-19 pandemic. As many of you know, I have been intimately involved in this arena, from both a natural medicine and public health perspective. One point I made early on is that what marks this infection as different than others is how it intersects with underlying chronic conditions of individuals and thereby impacts people in an acute way while also bringing to light or worsening more chronic complaints. One short statement I made was that in the first periods of the epidemic, most people will be focusing on mortality rates, on whether you live or die from this infection. But over time, as the next period begins, we will hear more and more about the chronic suffering that takes place. You may have heard about long haul syndrome and other diagnoses now made, long after the initial infection. This is where we are now.

In my personal practice with patients, I had often given them low dose lithium and zinc as a way to maintain proper health/normal functioning. However, since I also manufacture Lithia Basic, I could not publicize that as well, in terms of both perceived and potential conflict of interest. But the times are dire now. There are an increased number of people that are dealing with chronic neurological, cognitive, physical and emotional effects from COVID. I think this product would be useful for many to maintain normal functioning. But I cannot say that AND sell it. So I am stopping the manufacturing, distribution and selling of Lithia Basic, so that I can fully promote its contents, bought from other manufacturers and have no financial interest in any way. Most of these have not been tested against the virus, and I hope at a future time it will be.

As has always been written throughout The LITHIA WORKS website, you can buy these ingredients individually from numerous companies. These can be found by searching on the web for Lithium Orotate, low dose. The main problem is getting the ingredients in low doses, which is difficult. This means buying the product and then opening up the capsule. A tedious process. It may be that you can buy most of these as a liquid, and just take drops of them. Much less tedious process. Either way, it is doable. JUST KEEPING IT IN LOW DOSES.

Again, I apologize for this reality, but feel my highest calling is to provide actionable information to the broadest number of people and would like to do that free of any perceived conflict of interest. Thank you for your support and understanding.

With wishes for good health and vitality,

 Paul Herscu ND, MPH