[Sciences/Junk Sciences] Reconsideration of the immunotherapeutic pediatric safe dose levels of aluminum (Lyons-Weiler and Ricketson, J Trace Elem Med Biol 2018)

This is a post I wanted to write about a long time ago but for some reasons, I have been putting on the back burner for many different reasons.
You know what can be the most irritating to read? Papers from anti-science in general. You see, if the data was sound, the experimental setup was robust then I would consider their arguments are valid and sound. The problem with the anti-science papers I have been reading so far (anti-vaccines, anti-GMOs) are most of the time written by scientists that are lacking the expertise and credentials (in terms of publication record) to discuss on a topic, are based on speculation (the experimental data to support their hypothesis is at best paper-thin), the experimental data are most of the time missing the rigor and paradigm needed to make an objective outcome and often cherry-pick the literature.
Under normal conditions, such papers would not even pass a normal peer-review filter and would have been rejected outright. Yet, such papers found their way in very low impact factor journals or in predatory journals (that will publish any garbage study, as long as there is a valid payment method).

1. Who are the authors?
This is the case of this manuscript written by James Lyons-Weiler and Robert Ricketson. In this study, they claim that the current immunization schedule is dangerous, blaming on the extraordinary amount of aluminum and using questionable and speculative pharmacokinetics to support their claims (of course, there is no experimental data to support their claims, only speculation). A tenet in scientific publication is to assess how credible the authors are in the field, this can be judged by the authors affiliation and publication records. James Lyons-Weiler has  (according to his LinkedIn profile) a PhD in Ecology, Evolution and Conservation Biology and currently affiliated to the “Instittute for Pure and Applied Knowledge”. This is not a scientific institute as the Salk Institute, but rather an frontstore for some quackery posing as a “scientific institute”. The second author, Robert Ricketson, is no better. Indeed, he is even worse. Apparently Dr. Ricketson has a history of medical malpractice as a spine surgeon, and has been implicated in a medical malpractice lawsuit in 2001 for inserting a screwdriver in a patient spine. At the publication date, Ricketson affiliation is another “scientific institute” named “Hale O’mana’o Research” in Edmond, OK. A quick verification on his LinkedIn profile suggest that these two Ricketson are the same Ricketson. To summarize, we have two authors with ZERO expertise in pharmacokinetics (including one doctor that got fined over $5 millions for medical malpractice), working in institutes with questionable scientific credientials but established anti-vaccine stance, under the disguise of “vaccine safety” (here and here), published in a journal in which a notorious anti-vaccine scientist is sitting in the editorial board. Is it surprising? For me, it is not. Just a classical MO for anti-vaccine scientist.

2. What the paper is about?
You can find the paper here, since it is behind paywall I cannot legally share the information, so I would request the reader to corroborate my claims by getting the full-text. In this study, the authors consider the safety studies done in animals are not correct and underestimate the toxicity of aluminum because they are based on animal body weight. And thats where the trouble start. The authors solely consider the amount of aluminum injected into animals and patients SOLELY based on the body weight.
They ignore the administration route, they ignore the existing literature and even questions the outcomes and recommendation of the World Health Organization as mentioned as “We found two important errors in the provenance and derivation of provisional aluminum intake levels from World Health Organization (WHO; Supplementary Material) which, unfortunately, led to overestimation of safe exposure levels.” That’s a bold statement by the beginning, coming from two non-experts in pharmacokinetics and toxicokinetics.
So how do they ended up using such claim? By using a derived version of the Clarke’s equation:

Child dose (mg) = Adult Dose (mg) * (child bodyweight (lbs)/adult bodyweight (lbs))

The Clarke’s equation is a common equation used for therapeutic dosing, as we commonly refer to administer doses as x mg/kg. Knowing the patient weight, you can easily calculate the dose administered.  This formula is great…….if you already know the target concentration (or the average plasma concentration) you aim to target. This is usually supported by empirical data and further confirmed by lab tests (you can dose the drug in the patient plasma and assess if such amount falls within the therapeutical window). But this equation tells you nothing about the pharmacokinetics of the drug, or about the bioavailability of the drug, or differences in the administration routes.
It only tells you one thing “How many miligrams of X should I administer to obtain a plasma concentration of X falling into therapeutical range?” That’s it. You assume a dosing regimen (mg/kg), you know your patient weight (in kgs) and thus you can obtain the dose needed (loading dose or maintenance dose).  However, the authors manipulated the equation to be able to transpose the minimal risk level from adults to children as the following:

CED (mg/kg)= HED(adult) mg/kg x [BW(child) (kg)/BW(adult) (kg)]

The rest of the paper is SOLELY based on speculation, no experimental data to support the claim (we rather have a post hoc ergo fallacy unfolding). If the authors wanted to make their claims valid, they would provide experimental data (in forms of blood sampling) for 2 months babies before immunization (baseline control) and 6-24 hours after immunization to show that Al levels in plasma are significantly altered by the immunization. But they never show that data.
Indeed, what they show is a blatant misuse of the data and recommendation of the FDA and a serious miscalculation that a 12th grader would not even do.
They compared the dietary MRL as “JECFA provisional tolerable daily intake from dietary and additive exposures of 140 μg/kg/day and current provisional tolerable daily intake of 290 μg/kg/day per day both before and after the safety factor of 10 is applied (Fig. 3).”
We end up in the classical cases of “apples versus oranges” and trying to make the claim they are the same. Which they are not. Yes, both are extravascular routes and follow similar fate. But in the same time, we have to compare the physics-chemical aspects and the bioavailability of Al in both routes. One is administered by oral route, the other by intramuscular route. In both cases, the bioavailability falls within the same range, with the oral showing about 0.3% and the IM from 0.6% (based on Flarend et al., Vaccine 1997) and 0.9% (Yokel and McNamara estimate, Pharm Tax 2001).

What the authors show us is basically a graph that assume the WHOLE Al injected in 100% bioavaialable at once, exceeding the MRL adjusted to pediatrics) as seen in Figure 4:

There is one thing to consider: The ATSDR. The ATSDR considers the MRL of 1mg/kd/day of ingested aluminum (that is about 100x lower than the NOAEL and adjusted to the bioavailability, as described here: https://www.atsdr.cdc.gov/toxprofiles/tp22-c8.pdf). If we assume a bioavailability of 0.3%, then we expect that out of 1mg/kg/day ingested, we can estimate that about 3microg (or 0.003mg)/kg/day would contribute in the total burden in the Al plasma level. This graph would be correct if 100% of the aluminum injected ended up in the systemic circulation at ONCE and spiked Al levels significantly high. But thats not the case, and the authors blatantly ignored this critical information, coming from previous studies. In order to compare these two items, you have to compare and estimate how much of each of these routes will contribute in the total Al plasma/blood levels.
You cannot just plot the total amount injected (adjusted per kg) and assume it is representing the same variable than estimated plasma levels from the MRL. Now, let consider that the Al injected is available at the rate of 1% a day, the graph will look more like that.

You see, we have a complete different scenario. If we consider that the aluminum is slowly released into the body at a rate of 1% per day we are now being way under the MRL and within safe levels. Again, we consider the MRL of 1mg (1000microg)/kg/day. If we consider a 0.3% bioavailability and difference in 5th and 95th percentiles weight (grey bars), we conclude that the daily burden of Al via dietary route should not exceed a value ranging from 13.20-18.72microg/day. Our values matches the MRL from Lyons-Weiler. In other words, our assumption is correct. If we consider an average weight of 5.35kg (50th percentile) at 2 months and 1mg as a cumulative dose of the immunization occurring the same day (conservative estimate), the amount delivered that day would be 0.187mg or (187microgram). Considering a bioavailability of 1% per day via IM, we have about 1.87microgram of burden from the vaccine added each day to a maximum MRL of 16.05microgram/day for the 50th percentile (weight 50th percentile=5.35kgs). Thats about 11.7% aluminum to be removed from the daily MRL, but within negligible range to have a statistical significance (you need at least 30% to consider it as statically meaningful).  This of course has to be confirmed by studies assessing plasma levels of Al after injections but there are already a literature out there with such data avaialable and reported here and here. Both studies concluded no changes in total Al plasma levels in regard of the vaccination status, including 6-24 hours after immunization.

3. Concluding remarks

Anti-science know how to bangs for their bucks, by sensationalizing claims knowing that the lay person will not or be capable to verify their claim. Most of the times, such claims come from persons that are legitimate scientists in their field, but completely speak out of their expertise domain. This is a common trope we see when people cite Linus Pauling, Otto Warburg or Luc Montagnier. Each of them have done remarkable discoveries in their field, got their Nobel Prizes but once they speak outside their expertise have proven to be wrong or have seen their claims manipulated by quack-peddlers. Lets take Linus Pauling that has been incremental in modern chemistry by describing the chemical bonds, but later claimed cancer(s) can be cured with Vitamin C. Coincidentaly, he died of prostate cancer in 1994.
Same applies in this paper. We have two authors with ZERO knowledge of pharmacokinetics, yet they have given themselves the role to demonize aluminum at all cost, bending and occulting facts to fit their narrative and their conclusion. This paper is the evidence that they are not serious about “vaccine safety”. They are staunch anti-vaccines, and they will use their status of scientists to vilify it at all costs, even if it means reaching outside their expertise, make extraordinary claims without extraordinary evidences (they did not have evidence for this study) and get published in a journal that will favor their claims and obviously lacked the rigor in the review.
Negating the neurotoxic effects of aluminum is not a correct statement either. Aluminum is neurotoxic, but as anything in toxicology it is all about the dose. And one parameter that is critical to assess the safety of aluminum is its plasma level. This safety level is driven by how much aluminum access the systemic circulation (from IV parenteral nutrition bags or from extravascular routes such as vaccines or dietary exposure). What matter at the end is the Al plasma levels and the FDA set a limit on that daily exposure (5 micrograms/kg/day via IV route). This is a problem encountered by patients suffering from non-functional kidneys (95% of aluminum is cleared via renal route) and from patient continuously fed via IV route (total parenteral nutrition).
Both Lyons-Weiler and Ricektson failed to applied basic concepts of pharmacokinetics, ignored the differences between vascular and extravascular routes and willfully used a calculation method that is not appropriated for this purpose. I would even what is worse is that none of their claims is supported by hard data, making their claims even more questionable.
Unfortunately, such “junk paper” felt through the cracks of peer-review and has been used repeatedly used by anti-vaxxers as supporting evidence. As Andrew Wakefield has his second paper removed after 16 years, how long it will take to remove that paper?
I dont know but the damage is done, and until “vaccine safety” scientists come with robust and foul-proof studies published in highly respected journals, they will be considered by me and others as junk scientists, keeping on feeding the literature with their garbage studies that should have been wiped out by a rigorous peer-review process.