Antidote to NEJM Formaldehype Arrives at Last

In January 2015, R. Paul Jensen and colleagues created global headlines with a defective e-cigarette experiment (here).  They claimed in the New England Journal of Medicine that vapor contains “hidden” formaldehyde at far higher levels than cigarettes (here).  Their measurements required overheating or “dry-puffing” e-cigarette liquid, a process that produces such harsh (not hidden) oral sensations that the vapor is intolerable to normal consumers. 

As Churchill said, “A lie gets halfway around the world before the truth has a chance to get its pants on.”  The Jensen mischaracterization caused considerable damage, as it encouraged smokers to believe that vaping is more dangerous than smoking. 

Last week, the formaldehyde fallacy was laid bare.  Dr. Konstantinos Farsalinos and colleagues reproduced the Jensen experiment and found that “The high levels of formaldehyde emissions that were reported in [the Jensen] study were caused by unrealistic use conditions that create the unpleasant taste of dry puffs to e-cigarette users and are thus avoided.” Their work appears in Food and Chemical Toxicology (abstract here). 

Farsalinos’ group painstakingly reproduced the earlier experiment, using the same now-outdated vaping equipment that was prone to dry puffs.  First, they had experienced vapers identify at what settings the “burning” taste of a dry puff was detected: 4.2 volts, 8.0 watts.  They then used Jensen’s methods to measure formaldehyde at various voltage-power settings, seen in the chart (above) adapted from their publication.

Vapers detected dry puffs when the formaldehyde level was 100 micrograms (per 10 puffs).  Given that a microgram is one-millionth of a gram, Jensen’s formaldehyde level wasn’t hidden at all; at 380 micrograms, it was much higher than vapers could tolerate.  At lower, normal vaping power, formaldehyde was only 20 micrograms, or two-thirds that of cigarettes.

Farsalinos cautions the scientific community: “blindly testing e-cigarettes in the laboratory setting without evaluating realistic use is a serious omission that can result in misleading conclusions about the risk to consumers compared to smoking;” and such conclusions can wrongly imply “that there is little to be gained by switching to e-cigarettes.”

In response to the Jensen article in 2015, Clive Bates and Konstantinos Farsalinos published a letter in Addiction calling for its retraction (here); the demand was ignored.  The current publication is a much-needed antidote to Jensen’s seriously flawed and misleading findings.

Up in Vapor: The Real Story Behind the Formaldehyde-Cancer Link

Vapers, rest easy about e-cigarettes and formaldehyde. 

As a pathologist with 28 years’ formaldehyde exposure via workplace inhalation, I have both a professional and a personal interest in whether formaldehyde causes cancer.  It turns out that the formaldehyde-cancer link is weak to nonexistent, and it has been grossly exaggerated by organizations like the International Agency for Research on Cancer (IARC) and the U.S. National Toxicology Program (NTP).  In many ways, formaldehyde has been treated much like smokeless tobacco, which the same agencies list as a carcinogen in spite of weak to nonexistent epidemiologic evidence (here).    

The fact is, IARC and NTP primarily base their formaldehyde carcinogen classification on a single National Cancer Institute (NCI) study claiming that the agent causes nasopharyngeal cancer, or NPC.  That study, published in 2004 by NCI’s Michael Hauptmann and colleagues, has been shown to be unreliable.

The Hauptmann study was based on 25,000 workers, most of whom were exposed to formaldehyde at 10 industrial plants over a 30-year period.  Compared with unexposed workers, Hauptmann et al. reported that formaldehyde-exposed workers had about a two-fold higher risk for NPC, based on eight cases.  No other increased cancer risks were observed.   

The Hauptmann data was reassessed in 2005 by Gary Marsh, Ph.D., a University of Pittsburgh statistician who was supported by the Formaldehyde Council, an industry group. 

Dr. Marsh reported (abstract here) that “reanalysis provided little evidence to support NCI’s suggestion of a causal association between formaldehyde exposure and mortality from NPC.”  He pointed out that Hauptmann had based his conclusion on an excess of NPC in only one plant, located in Wallingford, Connecticut.  In the other nine plants, formaldehyde-exposed workers had lower-than-expected NPC rates.

Dr. Marsh continued to investigate the NPC cancers at Wallingford.  In 2007, he published another study showing that the NPC excess at the Wallingford factory was probably not due to formaldehyde, but to workers’ exposure “to several suspected risk factors for upper respiratory system cancer (e.g., sulfuric acid mists, mineral acid, metal dusts and heat).”

The NCI team had also claimed that the highest exposures to formaldehyde resulted in the highest NPC risks.  Dr. Marsh showed that claim to be wrong in a third study published in 2007 (here).     

In 2010, Annette Bachand and colleagues conducted a comprehensive meta-analysis, which included “all relevant cohort and case-control studies published through May 2009.”  They found no overall increase in NPC risk after excluding Hauptmann’s Wallingford plant data.  Six case control studies produced a marginally elevated risk for NPC among formaldehyde-exposed workers (OR = 1.22, 95% Confidence Interval = 1.00 – 1.50), which may have been due to a failure to adjust for smoking, a known risk factor for NPC.  Seven cohort studies resulted in a lower NPC risk among exposed workers (OR = 0.72, CI = 0.40 – 1.29). Bachand’s results were in agreement with an earlier meta-analysis by Bosetti et al.

Inflated claims by NCI epidemiologists are not unprecedented; witness the 1981 assertion by Dr. Deborah Winn that all American smokeless tobacco users were at risk for mouth cancer (completely refuted here and here).

The only bright side of this story is that the NCI formaldehyde-cancer claim could be analyzed because the agency’s data was available to outside investigators.  In contrast, the Karolinska Institute and the American Cancer Society have issued warnings about smokeless tobacco but persist in withholding the underlying data (here and here) – a violation of data-sharing and research practice standards. 

British Government Backs E-Cigarettes for Smokers

Public Health England last week became the first national government agency to endorse e-cigarettes as safer options for current smokers.  Its report also dispelled several bogus anti-tobacco claims.

PHE encourages smokers to switch to e-cigarettes in order to stop smoking and to reduce smoking-related diseases and deaths.  The agency strongly rejects the claim that vaping is a pathway to smoking: “There is no evidence that e-cigarettes are undermining the long-term decline in cigarette smoking among adults and youth, and may in fact be contributing to it.”

Additionally, PHE refutes scaremongering about nicotine poisoning (a subject I previously discussed here): “When used as intended, e-cigarettes pose no risk of nicotine poisoning to users, but e-liquids should be in ‘childproof’ packaging. The accuracy of nicotine content labelling currently raises no major concerns.”

I have noted that some researchers have fabricated claims that vapor contains dangerous levels of formaldehyde (here and here).  PHE rejects the assertion: “Two recent worldwide media headlines asserted that e-cigarette use is dangerous. These were based on misinterpreted research findings. A high level of formaldehyde was found when e-liquid was over-heated to levels unpalatable to e-cigarette users, but there is no indication that…users are exposed to dangerous levels of aldehydes.”

Unfortunately, the PHE report overreaches in one respect.  It says that “best estimates show e-cigarettes are 95% less harmful to your health than normal cigarettes,” and this became the dominant media headline upon the report’s release.  To be accurate, PHE should have reported that e-cigarettes are far less harmful than combustible cigarettes, without specifying a percentage; there is no hard data to support a number.

The 95% is derived from the reported opinions of a group of international experts in a publication last year.  The opinions were merely “guestimates”.  In truth, the health risks of long-term vaping are not known, and they are at this time unknowable.  While there is universal agreement among tobacco research and policy experts that inhaling a vapor of propylene glycol, nicotine and flavoring agents is vastly safer than inhaling smoke containing thousands of toxins, the precise risk differential is unknown.

I routinely criticize e-cigarette opponents for violating scientific principles when they make outrageous claims against the products.  Recognizing that the PHE report is a welcome endorsement of tobacco harm reduction and e-cigarettes, I am disappointed that its value is at all compromised by a comparison that cannot be scientifically validated.

Bogus Research on Formaldehyde in E-Cig Vapor

The New England Journal of Medicine yesterday published a letter claiming that vapor contains “hidden” formaldehyde at far higher levels than cigarettes (here), which made headlines worldwide.  That conflicts with a report I discussed last week, documenting that formaldehyde levels in e-cigarettes were far lower than those in traditional cigarettes (here).

R. Paul Jensen and colleagues at Portland State University produced the new results by overheating an e-cigarette, a condition (called dry puffing) that is familiar to vapers; the resulting product tastes so bad it cannot be inhaled.  In other words, the formaldehyde produced under abusive conditions is not “hidden” at all, because it is in vapor that users find intolerable.

Dr. Konstantinos Farsalinos, a cardiologist at the University of Patras in Greece and a recognized expert in vapor devices, has documented that the formaldehyde findings are bogus: “Lack of experience on e-cigarettes and no contact with vapers can result in such erroneous and unrealistic results, which can create confusion and misinformation both in the scientific community and among users and potential users of e-cigarettes… The authors of the NEJM study should have read our study and should have known about the existence of this phenomenon.” (here).

One of the new study’s authors, James Pankow, has published other scaremongering reports.  In 2010, he claimed that wintergreen flavor in smokeless tobacco is dangerous (here) and he coauthored a largely theoretical study claiming that “infants and children are particularly at risk” from thirdhand smoke. (here).

Modern automobiles have remarkably low pollutant emissions, but anyone behind a car that is overheating or otherwise abused can smell noxious fumes as they are released.  Using the New England Journal of Medicine, Jensen and colleagues have created global headlines with a defective e-cigarette experiment, producing scientific pollution.