Aluminium

Vaccines

What's The Problem?

Aluminium in vaccines acts as an "adjuvant" - it boosts immune response to vaccines, and so makes them more effective.

Aluminium is also a neurotoxin in sufficiently high doses.

The question is whether levels of aluminium in vaccines are safe.

What Do I Think?

The 2011 "Updated aluminum pharmacokinetics following infant exposures through diet and vaccination" paper gives, to me at least, a convincing argument that aluminium toxicity is not an issue on current schedules.

However, it also gives an interesting take on why Offit's famous Offit: 10,000 vaccines quote is so poor. You can't ramp up an aluminium-containing vaccine by 10,000 times. Of course Offit was talking about antigen load when he made his quote - but it gives a good example of how just saying "10,000 vaccines" without a very explicit qualification that we're talking about antigen load is misleading.

Background Papers

May 2009: ATSDR (Agency for Toxic Substances and Disease Registry)

PRIORITY DATA NEEDS FOR ALUMINUM

• PRIORITY DATA NEEDS FOR ALUMINUM
• Prepared by:
• Syracuse Research Corporation
• Under Contract No. 200-2004-09793
• Prepared for:
• U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
• Public Health Services
• Agency for Toxic Substances and Disease Registry

Absorption Rates:

• airborne: 1-2% absorbed
• food: 0.1-0.6% absorbed
• dermal: 0.01% absorbed

Pp 46-47: Gut is a strong barrier (blocks more than 99% of absorption)

Available data indicate that the gastrointestinal absorption of aluminum is often in the range of 0.1–0.6% in humans, although absorption of poorly available aluminum compounds such as aluminum hydroxide can be <0.01% (Day et al. 1991; DeVoto and Yokel 1994; Ganrot 1986; Greger and Baier 1983; Hohl et al. 1994; Jones and Bennett 1986; Nieboer et al. 1995; Priest 1993; Priest et al. 1998; Stauber et al. 1999 Steinhausen et al. 2004). Bioavailability of aluminum varies mainly due to differences in the form of the ingested compound and dietary constituents (i.e., the kinds and amounts of ligands in the stomach with which absorbable aluminum species can be formed). The apparent 10-fold or greater range in aluminum absorption has not been systematically documented using a variety of aluminum compounds and the most suitable analytical techniques. Radiochemical studies are desired because they facilitate accurate quantitation of the small percentages of ingested aluminum that are absorbed without requiring the use of large bolus doses and provide a means to trace administered aluminum and distinguish it from endogenous aluminum or from aluminum contamination of samples (Priest 1993). Additional toxicokinetic studies using 26Al would help to better characterize the likely range of aluminum bioavailability. Information on the bioavailability of aluminum in rodent laboratory feed would also be useful for extrapolating from animal to human exposure. Studies investigating the extent of absorption of aluminum into the placenta and fetal blood circulation would be useful in assessing the relevance of developmental effects in animals to human exposures.

2004: Aluminium toxicokinetics: an updated minireview

Aluminium toxicokinetics: an updated minireview.

• J Environ Monit. 2004 May;6(5):375-403. Epub 2004 Apr 23.
• The biological behaviour and bioavailability of aluminium in man, with special reference to studies employing aluminium-26 as a tracer: review and study update.
• Priest ND.
• SourceProfessor of Environmental Toxicology, Middlesex University, Queensway, Enfield, UK.

Abstract

Until 1990 biokinetic studies of aluminium metabolism and biokinetics in man and other animals had been substantially inhibited by analytical and practical difficulties. Of these, the most important are the difficulties in differentiating between administered aluminium and endogenous aluminium-especially in body fluids and excreta and the problems associated with the contamination of samples with environmental aluminium. As a consequence of these it was not possible to detect small, residual body burdens of the metal following experimental administrations. Consequently, many believed aluminium to be quantitatively excreted within a short time of uptake in all, but renal-failure patients. Nevertheless, residual aluminium deposits in a number of different organs and tissues had been detected in normal subjects using a variety of techniques, including histochemical staining methods. In order to understand the origins and kinetics of such residual aluminium deposits new approaches were required. One approach taken was to employ the radioisotope (67)Ga as a surrogate, but this approach has been shown to be flawed-a consequence of the different biological behaviours of aluminium and gallium. A second arose from the availability, in about 1990, of both (26)Al-a rare and expensive isotope of aluminium-and accelerator mass spectrometry for the ultra-trace detection of this isotope. Using these techniques the basic features of aluminium biokinetics and bioavailability have been unravelled. It is now clear that some aluminium is retained in the body-most probably within the skeleton, and that some deposits in the brain. However, most aluminium that enters the blood is excreted in urine within a few days or weeks and the gastrointestinal tract provides an effective barrier to aluminium uptake. Aspects of the biokinetics and bioavailability of aluminium are described below.

Papers In Support Of Safety

2002 Paper: Aluminum toxicokinetics regarding infant diet and vaccinations.

Aluminum toxicokinetics regarding infant diet and vaccinations.

• Vaccine. 2002 May 31;20 Suppl 3:S13-7.
• Aluminum toxicokinetics regarding infant diet and vaccinations.
• Keith LS, Jones DE, Chou CH.
• SourceAgency for Toxic Substances and Disease Registry, Division of Toxicology, Atlanta, GA 30333, USA. skeith@cdc.gov

Abstract

Some vaccines contain aluminum adjuvants to enhance the immunological response, and it has been postulated that this aluminum could contribute to adverse health effects, especially in children who receive a vaccination series starting at birth. The pharmacokinetic properties and end-point toxicities of aluminum are presented. In assessing the relevance of dietary and medical aluminum exposure to public health, we estimated infant body burdens during the first year of life for breast milk and formula diets and for a standard vaccination schedule. We then compared those body burdens with that expected for intake at a level considered safe for intermediate-duration exposure. The methodology blends intake values and uptake fractions with an aluminum retention function derived from a human injection study using radioactive 26Al. The calculated body burden of aluminum from vaccinations exceeds that from dietary sources, however, it is below the minimal risk level equivalent curve after the brief period following injection.

2011 Paper: Updated aluminum pharmacokinetics following infant exposures through diet and vaccination.

Updated aluminum pharmacokinetics following infant exposures through diet and vaccination. (Pubmed)

Full paper here

• Vaccine. 2011 Nov 28;29(51):9538-43. doi: 10.1016/j.vaccine.2011.09.124. Epub 2011 Oct 11.
• Updated aluminum pharmacokinetics following infant exposures through diet and vaccination.
• Mitkus RJ, King DB, Hess MA, Forshee RA, Walderhaug MO.
• SourceOffice of Biostatistics and Epidemiology, USFDA Center for Biologics Evaluation and Research, 1401 Rockville Pike, HFM-210, Rockville, MD 20852, United States. Robert.Mitkus@fda.hhs.gov

Notes

Gut absorption rate is 0.78%, as per here: Greger JL, Baier MJ. Excretion and retention of low or moderate levels of aluminium by human subjects. Food Chem Toxicol 1983;21(4):473–7.

Abstract

Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earth's surface. Exposure of the general population to aluminum occurs primarily through the consumption of food, antacids, and buffered analgesics. Exposure to aluminum in the general population can also occur through vaccination, since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants. Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants, we developed an up-to-date analysis of the safety of aluminum adjuvants. Keith et al. [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry. We updated the analysis of Keith et al. [1] with a current pediatric vaccination schedule [2]; baseline aluminum levels at birth; an aluminum retention function that reflects changing glomerular filtration rates in infants; an adjustment for the kinetics of aluminum efflux at the site of injection; contemporaneous MRLs; and the most recent infant body weight data for children 0-60 months of age [3]. Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infant's first year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL. We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns.

Conclusion

Using the previous work of Keith et al. [1] as our starting point, we re-evaluated aluminum levels in infants using a number of updated parameters, including a current pediatric vaccination schedule, baseline aluminum levels at birth, a recent aluminum retention function from human volunteers that incorporates glomerular filtration rates in infants, an adjustment for the kinetics of aluminum efflux at the site of injection, the most recent MRL for aluminum, and up-to-date infant body weight data for children 0–60 months of age. Assuming slow release of aluminum adjuvant from the site of injection into the systemic circulation, we have demonstrated that aluminum levels in infants are well below the minimal risk level curves for either median or low-birth weight babies. We also compared the body burden of aluminum contributed by vaccines with that contributed by diet. The body burden of aluminum from vaccines is not more than 2-fold higher than that received in the diet. While the contribution of vaccines to an infant’s aluminum body burden can be slightly higher than that of the dietary contribution in our model, the fact that the primary pool where the aluminum is residing, as a long-term storage depot, is likely to be skeletal and not a more sensitive soft organ system is reassuring [5]. Although aluminum toxicosis is known to occur in humans, it is found exclusively in individuals suffering from kidney disease or in those exposed to high levels of aluminum via occupational inhalation. However, for infants, our study demonstrates that there is little risk for aluminum toxicity following immunizations administered according to ACIP recommendations even with maximal exposures to aluminum adjuvant. For the general population of infants, who receive less than the maximal dose, the risk is even lower.

Papers Not Supporting Safety

2011 Paper: Aluminum Vaccine Adjuvants: Are they Safe?

Aluminum Vaccine Adjuvants: Are they Safe?

• Current Medicinal Chemistry, 2011, 18, 2630-2637
• Aluminum Vaccine Adjuvants: Are they Safe?
• L. Tomljenovic*,1 and C.A. Shaw2
• 1Post-doctoral fellow, Neural Dynamics Research Group, Department of Ophthalmology and Visual Sciences, University of British

Columbia, 828 W. 10th Ave, Vancouver, BC, V5Z 1L8, Canada

• 2Professor, Departments of Ophthalmology and Visual Sciences and Experimental Medicine and the Graduate Program in

Neuroscience, University of British Columbia, Vancouver, British Columbia, 828 W. 10th Ave, Vancouver, BC, V5Z 1L8, Canada

Abstract

Aluminum is an experimentally demonstrated neurotoxin and the most commonly used vaccine adjuvant. Despite almost 90 years of widespread use of aluminum adjuvants, medical science’s understanding about their mechanisms of action is still remarkably poor. There is also a concerning scarcity of data on toxicology and pharmacokinetics of these compounds. In spite of this, the notion that aluminum in vaccines is safe appears to be widely accepted. Experimental research, however, clearly shows that aluminum adjuvants have a potential to induce serious immunological disorders in humans. In particular, aluminum in adjuvant form carries a risk for autoimmunity, long-term brain inflammation and associated neurological complications and may thus have profound and widespread adverse health consequences. In our opinion, the possibility that vaccine benefits may have been overrated and the risk of potential adverse effects underestimated, has not been rigorously evaluated in the medical and scientific community. We hope that the present paper will provide a framework for a much needed and long overdue assessment of this highly contentious medical issue.

Some points in the paper

• Aluminium impact per kg of body weight: An infant receiving 1 HepB injection at birth = 10 adult Hep B doses
• Aluminium impact per kg of body weight: Injections at 2 months on the US schedule = 34 adult Hep B doses

Data

Estimated total aluminum body burden (μg/kg bw/day) per vaccination session in various developed countries. Vaccine schedules were obtained from the following sources: U.K. (U.K. Department of Health [10]), U.S. (Centers for Disease Control and Prevention [9]), Canada (Public Health Agency of Canada [57]) and Australia (Australian Government Department of Health and Aging [58]). Aluminum content of vaccines was according to Offit and Jew [3]

Birth	1 mo	2 mo	3 mo	4 mo	5 mo	6 mo
U.K.	73.5	62.5	245	184	193	0	0
U.S.	73.5	0	245	0	171.1	0	161.2
Canada	73.5	0	220	0	193	0	111.8
Australia	73.5	0	220	0	193	0	144.7

FDA safety limit for Al from parenteral sources: 5 μg/kg bw/day.

Table 3. Comparison of aluminum body burden from vaccines in children and adults. Note that the closest an adult can get to the aluminum body burden from vaccines that compares to that of a child is in special circumstances, such as Gulf War deployed military personnel. Each anthrax vaccine administered to Gulf War veterans contained 1200 μg Al/mL (600 μg Al/dose) [59]. Currently licensed hepatitis B vaccines Engerix-B and Recombivax contain 250 (pediatric) and 500 μg Al/dose (adult) [3]. Age-specific weights were sourced from Haddad and Krishnan [60]

	An infant receiving 1 HepB injection (250 μg/dose) at birth	A 2-month old receiving the full U.S. scheduled set of injections	An adult receiving 6 anthrax injections over 18 months	An adult receiving 73.5 μg/kg bw/visit from HepB at 500 μg/ dose	An adult receiving 245 μg/kg bw/visit from HepB at 500 μg/ dose
Total Al (μg)	250	1225	3600	5145	17,150
Bw (kg)	3.4	5	70	70	70
Total Al μg/kg bw/day	73.5	245	51.4	73.5	245
# of Al-adjuvanted HepB at 500 μg /dose	NA	NA	NA	10	34

Dr Sears

A reasoned sceptical position

On the source of the safety limit

Where does the 4 to 5 mcg per kilogram per day safety limit come from? I found a very interesting study from the New England Journal of Medicine 1997 (See Resource 4) that compared the neurologic development of about 100 premature babies who were fed a standard intravenous feeding solution that contained aluminum with 100 premature babies who were feed the same solution, but with almost all the aluminum purposefully filtered out. What prompted this study (as discussed in the study's introduction) was the knowledge that aluminum can build up to toxic levels in the bloodstream, bones, and brain when injected, that preemies have decreased kidney function and have a higher risk of toxicity, that one preemie with sudden, unexplained death had high aluminum concentrations in the brain on autopsy, and that toxicity can cause progressive dementia. So these researchers sought to prove that aluminum may be harmful to preemie babies. They turned out to be right. The infants who were given IV solutions with aluminum showed impaired neurologic and mental development at 18 months, compared to the babies who were fed much lower amounts of aluminum. Those who got aluminum received an average of about 500 mcg of aluminum spread out over an average of 10 days. This comes out to about 50 micrograms per day. The babies who got the solution with aluminum filtered out received about 10 mcg daily, or 4 to 5 mcg per kilogram of body weight per day. This seems to be where this safety level originated from.

Now, none of these documents or studies mention vaccines. They only look at IV solutions and injectible medications. I'm not sure why that is. Nor is it clear why the FDA does not require aluminum warning labels on vaccines when they do require it on all other injectible medications. Vaccines apparently have some sort of exemption.

All these warnings seem to apply mainly to premature babies and kidney patients. What about larger, full-term babies with healthy kidneys? Using the 5 mcg/kg/day criterion from the first document as a minimum amount we know a healthy baby could handle, a 12-pound 2-month-old baby could safely get at least 30 micrograms of aluminum in one day. A 22 pound one-year-old could get at least 50 micrograms safely. Babies with healthy kidneys could probably handle a lot more than this, but we at least know they could handle this amount. However, these documents don't tell us what the maximum safe dose would be for a health baby or child. And I can't find such information anywhere. This is probably why the A.S.P.E.N. group suggests, and the FDA requires, that all injectable solutions have the 25 mcg limit, since we at least know that is safe.

On Whether There's A Problem

If I could sum up the aluminum controversy in three sentences, it would be this. There is good evidence that large amounts of aluminum are harmful to humans. There is no solid evidence that the amount of aluminum in vaccines is harmful to infants and children. No one has actually studied vaccine amounts of aluminum in healthy human infants to make sure it is safe. Should we now stop and research this matter? Or should we just go on and continue to hope that it is safe?

On How To Settle The Question

Aluminum toxicity, as the FDA, AAP, and others have stated, can't be noticed just by external observation. It would really be a shame to have several such reports show up in the medical literature just to try to put a lid on this issue. The only way the aluminum safety issue can be put to rest is for someone to conduct several real-time studies on thousands of human infants and measure aluminum levels after vaccination. And they should not just look at blood levels. They should find out where aluminum accumulates in the body, if at all, and how it is eliminated from the body and at what rate.

Levels In Food (And Why They Aren't Relevant)

Why This Isn't A Useful Argument Either Way

A common line is to contrast aluminium in vaccines with aluminium in food/drink.

However the vaccine sceptic argument is that food/drink comes up against the gut barrier, which ensures the vast majority of ingested aluminium never reaches the bloodstream - more than 99% is not absorbed.

For this reason, arguments based on Aluminium levels in the diet are not a convincing counter-argument to the vaccine sceptic line.

Typical Figures

A typical site is here: Oxford Vaccine Group - Vaccine Ingredients

Quantity of aluminium in vaccines (per dose) compared with baby milk (per 1000ml, an average daily amount for a 2 month old baby)

Vaccine Brand name	Aluminium (μg)	Type of milk Aluminium	(μg)
5-in-1 DTaP/IPV/Hib vaccine Pediacel	330	Breast milk	40
PCV Prevenar13	125	Infant formula	225
MenC vaccine Neis Vac-C	500
Meningitec	125
Menjugate	400

Quantity of aluminium in vaccines (per dose) compared with foods (per 100g)

Vaccine Brand name	Aluminium (μg)	Food	Aluminium (μg)
Hib/MenC Menitorix	0	Cornflakes	410
MMR vaccine MMRVaxPro	0	Avocado	390
Pre-school booster vaccine Repevax	330	White Bread	220
HPV vaccine Gardasil	225	Spinach	970
Cervarix	500	Brussels Sprouts	420
Teenage booster vaccine Revaxis	350	Parmesan	2000