www.biology.chapsonline.org.uk/documents/10432_7PoppersSSR.pdf UK 2007 Gay Men's Sector Summary Report on Poppers. Cites limitations of the research showing that poppers use effects the immune system. Fails to cite and reference the published research showing that poppers effect the immune system. Critical analysis of this report is at bottom of this page. see *****
www.biology.chapsonline.org.uk/poppers.aspx Dr. Neil MacDonald, UK researcher of INSIGHT which found poppers use to increase HIV transmission
http://sfhiv.org/substance_use_resources_drugs.php 2008 San Francisco Health Department Office of AIDS Fact Sheet: Poppers & HIV (Word)
www.metrokc.gov/health/apu/infograms/poppers.htm 2007 Seattle Health Department Poppers Alert
www.homohealth.org/mens_program/sexualhealth/poppers.htm#popperssurvey Seattle 2006 Survey
www.tht.org.uk/informationresources/publications/gaymenanddrugs/poppers833.pdf London's Terrence Higgins Trust, poppers pamphlet, 2007
www.homohealth.org/mens_program/sexualhealth/poppers.htm Seattle project directed to gay men
www.dancesafe.org/documents/druginfo/poppers.php.org Harm reduction information
www.dancesafe.org/newlit.php poppers information card: click on picture of card at bottom for blow up
www.gaylib.com/aids/aids20.htm Poppers Information Pamphlet. This initial poppers education pamphlet was produced in 1985 in San Francisco and some of the information and perspective remains relevant.
www.nida.nih.gov/PDF/RRinhalants.pdf National Institute of Drug Abuse - page 7 = nitrite inhalants
***** Critical Analysis of the UK Sector Summary Report on Poppers
The UK Sector Summary Report on Poppers references and relies upon Lisa Ringold's critical overview of the research done on poppers found at www.virusmythpoppersmyth.org/hank_wilson_references. The items below are the issues raised and a response to them.
In the section "Poppers and Immune Suppression":
"Many of the research studies investigating the impact of poppers on immunity come with caveats or methodological flaws such as:"
1. Issue: "data is not published in respected peer reviewed medical journals"
Response: The attempt of the bibliography is to be comprehensive with listings of publications, abstracts, and submissions that come to our attention. A goal has been to compile information for use by consumers,service providers, policy makers,historians, and researchers.
Peer reviewed journals cited in the bibliographies:
AIDS AIDS and Behavior AIDS Care AIDS Education and Prevention
American Journal of Epidemiology American Journal of Medicine
American Journal of Public Health BMC Public Health Cancer Immunology and Immunotherapy
Cancer Research Clinical Infectious Disease Clinical Toxicology Drug and Alcohol Dependence
Experimental Hematology Immunopharmacology and Immunotoxicity
International Journal of Immunopharmacology Journal of Acquired Immune Deficiency Syndrome
Journal of Clinical Virology Journal of Infectious Diseases Journal of Leukocyte Biology
Journal of National Cancer Institute Journal of Neuroimmunology Journal of Psychoactive Drugs
Journal of Substance Abuse Journal of Urban Health The Lancet New England Medical Journal
Pharmacotherapy Sexually Transmitted Diseases Sexually Transmitted Infections
Substance Use and Misuse
Non peer reviewed journals are also cited in the bibliographies. These journals have editors and editorial boards with expertise:
Advances in Experimental Medicine and Biology
Advances in Biochemistry and Psychopharmacology
Biochemistry and Biophysical Research Communications Genetica
Environmental and Molecular Mutagenesis Fundamental and Applied Toxicology
Journal of Toxicology and Environmental Health Journal of Toxicology and Clinical Toxicology
National Institute of Drug Abuse Monograph National Toxicology Program Technical Report Service
Neurobehavioral Toxicology Teratology Nitric Oxide
Research Communications of Chemistry, Pathology and Pharmacology
Abstracts presented at scientific conferences have also been included. Unpublished material is included with "unpublished" disclosed. Abstracts are included to give a historical perspective and to foster timely dissemination of information. the delay of publication subsequent to abstract presentation can take years. It took almost 8 years in one case after the abstract originally surfaced at an International AIDS Conference before it was published in a peer reviewed journal. Some research which is presented at inaccessible conferences as abstracts or presentations is never submitted for publication, or it might never get accepted. We have prioritized timely dissemination of information. Our goal is to present the information so that it can be evaluated and utilized.
2. Issue: "study samples are usually small"
Response: Unfortunately True. Funding limits impact research.
3. Issue: "study results may include preliminary,unconfirmed data or findings not obtained in repeated trials"
Response: Timely dissemination of information is a priority. Time between conference and abstract presentation until publication can be quite long In one case, we included the abstract not knowing it would take over 7 years before the same information was published in a peer review journal. We presented a few studies that were never submitted for publication. Research citations are included that was submitted but not accepted for publication. In each case there is disclosure of the unpublished status to assist evaluation.
Funding limitations,disinterested researchers, researchers that are "too busy" or have "moved on to other things" and unprioritized status have resulted in lack of repeated trials.
4. Issue: "Poppers may be injected into the bloodstream, not inhaled"
Response: Over 20 studies involved mice inhaling poppers, the Dax human studies involved humans inhaling poppers. One study, Maickel 1979, involved only injecting poppers into mice.
5. Issue: "quantity and duration of exposure to poppers can be much greater than typical in recreational use"
Response: The Dax study was designed to simulate an episodic pattern of poppers use. The safety monitoring committee limited the number of inhalations per inhalation session to minimize harm to participants. It was recommended that participants take multiple inhalations in each inhalation session, but the safety committee rejected this recommendation and also refused to allow HIV positive participants less they be permanently harmed.
The Dax human study had two groups, a short study and an extended study. All volunteer gay male participants lived at the closed Addiction Research Center research ward for at least 10 days before two baseline immune profiles which were performed 3 days apart. The ARC research ward is a closed medical facility where the residents' urines are monitored daily to exclude the possibility of surreptitious drug use. All participants had previously used volatile inhalants(poppers), but none had done so in the six months preceding this study. The extended study had participants take one inhalation on the first and third day of the week, for two weeks.Initially participants in both groups took one inhalation 3 times a day for 3 consecutive days. The inhalation schedule was one inhalation at 9AM, noon, and 3PM. The short study inhalations stopped after 3 days. The extended study continued with participants taking one inhalation on the first and third day of the next two weeks. The extended study participants took a total of 13 inhalations during the study period.
Dax: "Single inhalations at 3-4 day intervals result in sustained depression of natural killer activity.Further, our results suggest that chronic exposure to inhaled nitrites, even at relatively infrequent intervals, is sufficient to produce longer lasting alterations in lymphocyte function.""The doses of nitrites administered to the volunteers in this study are moderate compared with those reported by individuals abusing isobutyl nitrite."
There is a wide variation in "typical recreational use." Quantity of use could range from a couple inhalations to a couple dozen inhalations in a use episode. We recommend another human study which more closely matches recreational use patterns. This would include a range of multiple inhalations in a use episode.
6. Issue: " adjustments are often not made for the difference in body mass between rodents and humans"
Response: Toxicology assessment of drugs uses animals to minimize risk to humans. Dose, quantity and duration of exposure are likely factors in development of toxic effects. The scientists conducting the studies on the effect of poppers on the immune system are from multiple institutions and have published their work in multiple peer review journals. The research results taken as a whole, point in the direction that poppers impact the immune system. The significance of the impact would likely be affected by quantity and duration of dose.
7. Issue: "studies frequently involved rodents(some genetically altered to have no immune defences) not humans"
Response: Dax conducted the human studies in 1987. There have been over 20 mice studies with only one of those studies involving genetically altered mice with no immune defence. Toxicology assessments typically involve rodents to minimize harm to humans.
8. Issue: "studies may be conducted on blood cell cultures in the test tube, not in live subjects"
Response: Some of the early studies were blood cell cultures in the test tube: Maickel RP 1979; Quinto I 1980; Hersh EM 1983; Kaled M 1986; Maickel R 1988; Dunkel V 1989.;Mirvish S 1993;
Dax conducted 2 human studies in 1987: Dax E 1988; 1991.
About 20 mice studies have been conducted: Fung HL 2006; Tran DC 2006; Soderberg LS 2004; Ponnappan U 2004; Tran DC 2003; Ponnappan U 2001; Keilbassa W 2000; Guo G 2000; Shafer R 1999; Soderberg LS 1999, 1997,1996,1994,1991; National Toxicology Program 1996; Ortiz JS 1988; Lewis DM 1988; Gangadharam PR 1985; Lewis DM 1985; Lynch DW 1985; Lotzova E 1984; Jacobs RF 1983; Watson S 1982.
9. Issue: " there is research suggesting poppers have no lasting significant effect on the human immune system"
Response: one published study is cited.
10. Issue: "and certainly no conclusive research shows any significant impact on human immunity. In fact, inhaled nitrites break down easily and quickly leave the body."
Response: Natural killer cell function was suppressed and it took 96 hours to return to baseline. Some would consider the Dax human study instructive that nitrite inhalants weaken the bodies natural defense system. If HIV or HHV-8 gets a foothold resulting in infection the impact is long lasting despite the nitrites having left the body.
11. issue: "There is an absence of robust evidence for poppers weakening the immune system. The great majority of studies involve animal, not human subjects, and much of this research is open to criticism for poor methodology. In studies suggesting a negative impact on immunity, there appears to be a modest suppression of CD4 cells(in mice) or natural killer cells (in humans) for 4-7 days following poppers use." "many factors affect immune function or CD4 count, including diet, exercise, smoking and time of day"
Response: suppressing natural killer cell function is important because it could allow HIV/HHV-8 infections to be established if someone is exposed during unprotected sexual exposure.