Radiation Cocktails: Fact or Fiction?
Human beings often go to extreme lengths to evade death. Each one of us knows that our clock is ticking, and we have only a finite amount of time to figure things out or at least have a good time trying. We obsess about our sleep, our exercise, the pollutants in our environment and food sources, or, on less demanding days, how best to relax from the grind. And what better way to do the latter than to combine health-promotion with rest and recreation? In this vein, we have invented the strange, mysterious, but nonetheless riveting practice of flirting with disaster in order to avoid it altogether. And we call this exotic pastime – hormesis.
The principle of hormesis
Hormesis is based on the idea that what may be your poison at a very high dose could otherwise end up doing you good in small amounts. Moreover, those small brushes with malady might even have the opposite effect of a full-blown overdose. And this sweet spot for beneficial outcomes goes by the name of “the hormetic zone”. It is that land of paradoxical magic where low levels of toxins or stress might actually energize you, increase vitality, and prolong your life. Interested in taking a vacation in this wonder zone? Well you are quite in luck: there are many travel packages.
Doing a balancing act on the hormetic tightrope is actually not a new idea: it was in ancient Greece that the word was first coined to described “eagerness and rapid motion”. That is, we use what is dangerous in our environment to provoke the body’s desire for quick change or adaptation. In toxicology, this change is characterized by comparing responses from low to high doses and charting a J-shaped or inverted U-shaped curve. The apex of that curve typically represents the optimal response, after which increased dosing will only produce adverse effects. So in the world of hormetic “biohacking”, we start with a low dose and gradually titrate up until things begin to “go sour”. Somewhere in between will give us the effect we are looking for.
While we still don’t have a full grasp of how hormetic mechanisms work, we’ve none the lest gone quite wild with every manner of experimentation. The most well known example of the hormetic zone is, of course, exercise. Studies have shown increased oxidative stress with both sedentary and “Crossfit Generation” lifestyles. Whether you prefer sitting in a comfortable lounge chair, eating potato chips, and watching re-runs or find yourself strapping redwood trees to your back with metal chains and running marathons, the outcome will be nearly the same: a shortened lifespan.1
Alcoholic beverages are another perfect example. Strong correlations have been made with alcohol consumption and a hormetic dose-response curve for all causes of death, including cardiovascular disease and cancer. One 2005 study claimed that a moderate alcohol intake of 0.1–22.9 g/day (i.e. 1-2 drinks) could decrease death risk by as much as 20% relative to non-drinkers. Pounding away a bottle or two (or ten) of Merlot per day, however, was associated with a statistically significant 40% elevation in all-cause death risk and likely terrible errors in judgement as well (but the latter is purely idle speculation). For those that follow trends in the press, there was a significant spike in blog, news, and magazine articles praising the benefits of a glass of wine per day. This praise was not warmly extended to wine’s distant cousin, hard liquor, but one can only assume many of the most faithful began downing their customary daily shots with more vigor and certitude as well.
But what if your beverage of choice was spiked with ionizing radiation? Would you jump on that bandwagon? Would you be surprised to learn people did just that over a century ago?
The ionizing radiation “health fad”
Back in the early 1900s, radioactivity was a hot topic. It was widely promoted as a cure-all for many ailments and many therapies ranging from uranium blankets to thorium-laced digestive aids were in vogue all around the globe. Conclusions about the safety of irradiated remedies were drawn upon early measurements taken at natural, healing “hot springs”. Radiation detectors showed high levels of radon gas in the waters there produced from thorium and uranium decay deep in the earth. Many individuals had been cured of various disease by bathing in these springs, so the researchers quickly jumped to the conclusion that radon must be behind the beneficial effects.
These faulty conclusions gave rise, unfortunately, to an increase in “radiation drinks” offered by eager yet ill-informed would-be entrepreneurs. We saw the issue of many (now) shocking products such as the Radium Ore Revigator, a uranium-radium ore lined watercooler boasting the ability to emit radon into water. At the same time, William John Aloysius Bailey, a Harvard University dropout claiming to be a doctor of medicine, founded Baily Radium Laboratories, which marketed radioactive radium as a cure for cough, flu, and other such ailments. Mr. Bailey was famous for offering $1,000 to anyone that could prove that his “certified radioactive water” (trade name Radithor) did not contain the generous amounts of radium and thorium claimed in the advertisements.
Radithor was a hit, incidentally — until — in a 1932 edition of the Wall Street Journal, it was revealed that one of its avid consumers, an industrialist by the name of Eben Byers, died from it. The headline was “The Radium Water Worked Fine until His Jaw Came Off.”2
If at first you don’t succeed…
Lest we get carried away with history, lets not lose site of the fact that the anecdotes shared above clearly overstepped the U-curve for hormetic benefit. Being that humans tend not to learn from their mistakes, scientists have continued to study the potential hormetic effects of ionizing radiation in a variety of scenarios with inconsistent results. In one 2008 Taiwanese study, 10,000 peopled were studied for 10 years, inhabiting 100 apartment buildings constructed from recycled radiocontaminated steel. These unsuspectingly lucky residents were getting a modest 50 mSv/year and a 1,000 of them even went as high as 4,000 mSv over ten years. Expected cancer rates for this population were 302, 70 of which would have been caused by natural background radiation. Surprisingly, however, only 7 people died. The conclusion was made that ionizing radiation hormesis was the “protective factor”.3
It should be obvious to the keen reader that the Taiwanese scientists committed a similar error in judgement to the investigators measuring radon levels in hot springs a century ago. The absence of cancer and the presence of low-grade ionizing radiation was automatically correlated to a “hormetic zone effect”. Nonetheless, Taiwan’s National Cancer Registry published a follow-up report showing increased risks of developing certain cancers in specific subgroups of the study’s population.4
Unfortunately, not two years after that publication, the same Cancer Registry declared significant radiation risk for leukemia and a marginally significant dose response for breast cancer. It would seem that all was not entirely joyful in hormetic paradise. Nonetheless, effects of low-dose ionizing radiation have continued to capture the ire and zealous ambition of many a scientist since then.5
DNA repair mechanisms are fallible
Studies abound in the last 20 years demonstrating an increase in gene expression for chromatin-associated enzymes governing the response to low-dose radiation. Two of the most well-studied of these enzymes are PARP-1 and PARP-2, which are involved in the base excision repair pathway. This pathway removes small, non-helix-distorting base lesions from the human genome, thereby avoiding mutations due to mispairing or lead-to breaks in DNA during replication.
ATM (ATM Serine/Threonine Kinase) also serves as a DNA damage sensor. It activates checkpoint signaling during double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA). Upon detection of a double-strand break, the checkpoint is leveraged to repair the severed double-helix with mechanisms such as non-homologous end joining (NHEJ), microhomology-mediated end joining (MMEJ), and homologous recombination (HR). NHEJ, in particular, is in part mediated by XRCC6 (X-Ray Repair Cross Complementing 6), also known as Ku70, an ATP-dependent helicase.
Reading the literature on these various chromatin-associated enzymes and repair factors, one could become quite enamored by the possibility that highly reliable mechanisms are in place to repair damage done by low-dose ionizing radiation. Emboldened with this knowledge, it might even be possible to consider eating radioactive contaminated acquatic species such as those found in the Pacific Ocean after the Fukushima reactor’s release of radionuclides after the 2011 incident. But before you jump off that cliff, take a moment to remember our predecessors both in the turn-of-the-century hot springs and the Taiwanese apartment complexes. Where do we delineate a low dose from a high one?
In the best case scenario, your own individual genetic expression for PARP-1/2, ATM, Ku70, and the XRCC family of genes is free of polymorphisms and, if mutated, well methylated (i.e. silenced and sleeping). This would put your genome in an excellent position to defend itself against environmental insult from ionizing radiation. Nonetheless, it is well known that PARP-1 and 2, among other genes, are also expressed in actively divided tumor cells. As a matter of fact, PARP-1 inhibiors have been applied in the treatment of tumors by enhancing the efficacy of ultrafractionated or low-dose-rate radiotherapy regimens.6
This means that if, for a wide variety of reasons, your DNA repair mechanisms skipped a step, any amount of ionizing radiation, regardless of dose, could potentially create mutations that are carried through mitosis into the somatic cell line. Although this happens rarely in day to day cellular replication, frequency increaes over the course of a lifetime. And it is the hallmark of all oncogenic pathologies.
But how does your risk increase if your genome is not optimally expressed?
Polymorphisms in DNA repair mechanisms are well documented for Poly(ADP-Ribose) Polymerases (PARP1/2). They have been correlated with colorectal7, breast8, lung9, prostate, and ovarian cancers, Burkitt lymphoma10, medulloblastoma, and neuroblastoma.11 Oncologists that are familiar with the pathways governing the progression of these diseases will concur – the greater the genetic polymorphism in DNA repair genes, the greater the risk for faulty damage repair from ANY insult.
The problem with radioactive fish
Ken Buesseler, a radiochemist with the Woods Hole Oceanographic Institution, has raised concern about the continued levels of radioactive cesium in the waters of the Pacific Ocean. He indicates that 1% of the fish in the waters off of Fukushima are currently above the government’s seafood radiation limits. And yes, those breed and migrate. The radiation limits are down by over half since 2011, but does this mean that the fish caught off the West Coast of the United States are safe to eat, moreover liberally? Radioactive particles accumulate in the flesh of marine life, similar to methylmercury. The larger the organism, the greater its potential for toxin stores. Add to this problem this rather troublesome detail: at this time, there is no US federal agency responsible for studies of radioactive contaminants in the ocean.12
Knowing these facts, are you ready to roll the die without concretely knowing the levels of contaminants in the food you eat or the status of your DNA repair mechanisms? Remember, even if you did not inherit polymorphisms in these genes through the germ-line, somatic mutations directly to PARP-1 and 2, ATM, and Ku70 are still possible from any and all genotoxic stresses, not the least of which is ionizing radiation. The problem is simple: you cannot determine a U-based curve if you do not know the dose, absolutely.
In my mind, those that would invoke the studies listed above and interpret them as cart-blanche for the consumption of irradiated food sources does not understand this issue deeply enough. These are the same individuals telling people a century ago to drink radon-infused water for health benefits. You should hold them in the highest suspicion, as they are often chronically prone to draw quick, broad conclusions after only cursory reading or contemplation. Nobody anywhere in the world today can tell you, absolutely, that eating irradiated food is safe. You must learn to distinguish the helpful from the deleterious.
By discussing complex concepts surrounding DNA repair and environmental stressors, some experts would give you a strong (perhaps undeniable) impression that they understand how science on this matter is evolving. But as always, the more you know, the more you will be able to distinguish extrapolation and anecdotal hyperbole from critical scientific observation — and thereby — avoid driving your health off a cliff in search of your next “radiation cocktail”.
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