By Alan Cocchetto, NCF Medical Director © 2018

From Winter 2018/9 Forum

The “Just Ask.’ ” column is intended to act as a means for patients to inquire about issues related to the NCF ‘s research activities. This column is NOT intended to act as medical advice in any way, shape or form.’ The National CFIDS Foundation assumes no responsibilities for any action or treatment undertaken by readers. For medical advice, please consult your own personal healthcare providers.

Q: Could you explain further what radiation does to damage the human body?

A: Radiation damage occurs from several mechanisms with the relative contribution of each depending upon the amount of exposure. At very high doses, radiation causes cell death from direct DNA damage resulting in complete breakage of double-helical strands of DNA (also referred to as double-strand breaks or DSBs). However, as exposure levels decrease, other effects become significant. Among these are peroxidation processes due to the ionizing energy of radiation producing highly reactive free radicals, particularly associated with elemental oxygen (also referred to as reactive oxygen species or ROS), even in cells whose nucleus escapes direct assault. Reactive oxygen species are toxic because of their propensity to bind to and modify almost anything in their path which include proteins, lipids and nucleic acids. Over time, cells with significant levels of ROS can become as equally compromised as those with direct DNA effects. ROS damage can also lead to DNA abnormalities that eventually are lethal due to genomic instability. Thus, the amount of insult sustained by a cell will depend upon the dose of radiation received and will reflect a mixture of direct DNA damage, ROS damage, and indirect DNA damage due to ROS effects. The timing and extent of the overall damage to an organism then depends heavily on the dose of radiation received that results in a progressive non-linear relationship between survival and exposure. Because of these adverse effects on the cell, there really is no safe level of radiation exposure to humans.

A great example of this are NASA’s astronauts. Space missions expose astronauts to cosmic radiation.

In fact, the medical literature shows measurable increases in chromosome (DNA) damage in the blood of astronauts. Astronaut Scott Kelly’s year in space even altered his chromosomes and thus his DNA by comparison to his twin brother [1,2]. This is but one example of the side-effects of radiation exposure.

References:

1. Scott Kelly's Year in Space Changed His Gene Expression; Scutti S; March 15, 2018;
www.cnn.com/2018/03/14/health/scott-kelly-dna-nasa-twins-study/index.html

2. Scott Kelly: NASA Twins Study Confirms Astronaut's DNA Actually Changed in Space; Hignett K;
March 9, 2018; www.newsweek.com/scott-kelly-astronauts-nasa-dna-838535

Q: I read the NCF’s assessment of Dr. Robert Naviaux’s current research with Dr. Ron Davis ’ group at Stanford University and found the radiation connection rather intriguing. Is there other work being done there that connects Davis’ team at Stanford to the work being done by the NCF?

A: Great question! In the last Forum, the NCF outlined the direct connection between Naviaux’s efforts on the metabolic response identified in CFIDS patients and that of radiation exposure. As pointed out with the previously attached references, radiation produces this same exact response in mice/rat models! In fact, the NCF had been corresponding with Dr. Naviaux via email to inform him of this direct relationship and we have shared several discussions regarding this.

However, the NCF has more data that ties Davis’ work to that done by the NCF and I would encourage you to view the new video, presented by Dr. Davis himself at:
www.omf.ngo/2018/09/17/ron-davis-iimec13

In particular, see the figure showing uranium hair analysis at the 38 minute mark (approx) where Dr. Davis comments on this. Out of 11 patient results that are shared on the overhead, 4 of these patients had abnormal higher levels of uranium via hair analysis....
Be sure to listen to his comments on this.....

While only uranium was included in the hair analysis that Dr. Davis’ team pursued, the National CFIDS Foundation had previously tested for uranium as well as all the other alpha-radionuclides (polonium, thorium, radon etc.) via urine testing in its patient cohort. Our ‘net’ included all the high-LET radionuclides that we could test. In Davis’ overhead, U = uranium which represents just one specific alpha-radionuclide.

According to Reference #1 below, the paper (which the NCF sent to Drs. Davis and Naviaux), states:

"There can be no argument, however, regarding a connection between an elevated concentration of uranium in the hair and exposure of the hair to uranium....When the focus is on uranium exposure rather than uranium intoxication, the determination of uranium concentrations in hair can be a useful tool in the large-scale screening of populations for possible exposure to uranium."

From our perspective regarding high-LET intemal radiation exposure, it is possible that the Stanford group is a subset of our cohort since it appears that they have also identified an environmental association with uranium radionuclides. The National CFIDS Foundation first announced this association in 2010 then went on to pursue specific chromosomal analysis in our patient cohort where we identified high levels of chromosomal damage. The association between radiation exposure and the development of CFS was first identified by the scientists at Chemobyl and this has been widely published.

More recently, Dr. Wenzhong Xiao, a member of Dr. Davis’ group, identified several key metabolites that separated the severely ill CFIDS patients from controls. These included a significant decrease in indolepropionate along with a significant increase in both lysine and hydroxyproline [2]. These same alterations in these same metabolites have been previously identified in metabolomic radiation studies [3]. In addition, the NCF had identified and published on a CFIDS patient autopsy where we had identified a neurode generative tauopathy. This is very important since radiation exposure has already been linked to the development of neurodegenerative tauopathies in the medical literature.

In his video, Dr. Xiao goes on to explain the role of indolepropionic acid, which is made in the gut and it also acts as a neuroprotectant. ln fact, it also aids in inhibiting beta-amyloid fibril formation! This is in total agreement with the neurodegenerative tauopathy that the NCF had previously identified via an autopsy. Furthermore, the NCF identified two papers that are certainly applicable to this work that links the gut to indolepropionic acid to neurodegeneration[4,5].

As the NCF had stated previously, our cohort is fully represented by internal alpha-radiation exposure which leads to chronic radiation sickness with an increased risk for neurode generative tauopathy and cancer resulting from genomic instability and chromosomal abnormalities. The NCF’s researchers have many more publications in the pipeline and that is why we are very encouraged by what we are seeing in other research groups who act to confirm and reinforce our own research ?ndings.

References

1. Efficacy of hair analysis for monitoring exposure to uranium: A mini-review; J oksic AS, Katz SA;
J Environ Sci Health A Tox Hazard Subst Environ Eng. 2014;49(l3):1578-87.

2. Dr. Wenzhong Xiao; Results from the severly ill patient study (SIPS);
https://www.youtube.com/watch?v=_Nlo2gbaCl4   15minute mark

3. Metabolomic applications in radiation biodosimetry: Exploring radiation effects through small molecules; Pannkuk EL, Fomace AJ Jr, Laiakis EC; Int J Radiat Biol. 2017 Oct;93(10):l151-1176.

4. Human gut microbiota: the links with dementia development; Alkasir R, Li J, Li X, J in M, Zhu B; Protein Cell. 2017 Feb;8(2):90-102.

5. Development of indole-3-propionic acid (OXIGON) for Alzheimer's disease; Bendheim PE, Poeggeler B, Neria E, Ziv V, Pappolla MA, Chain DG; J Mol Neurosci. 2002 Aug-Oct;l9(l-2):213-7.