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Amid vape pen lung disease deaths: What exactly is vitamin E oil?

September 11, 2019
(HighGradeRoots/iStock)
Story updated Oct. 4, 2019

An unprecedented outbreak of vaping-associated pulmonary injury (VAPI) has sickened 1,80 people and killed as many as 20 in 48 states this summer.

One current suspect in the outbreak is vitamin E acetate, sometimes used as a vape cartridge additive. It’s a popular new diluent thickener found mostly in illicit market THC vape carts. What is vitamin E oil and what makes it dangerous? We explore below.

Vitamin E oil has natural or synthetic sources

Vitamin E is the common name for several similar types of chemicals called “tocopherols”. They’re commonly found in corn and other vegetable oil or made synthetically from petroleum. We often eat tocopherols as a dietary supplement, and manufacturers put tocopherols in food and cosmetics.

“No vitamin E should be vaped regardless of its chemical structure.”
Eliana Golberstein Rubashkyn, chief scientist, Myriad Pharmaceuticals

From various plant sources of tocopherols, chemists extract vegetable oil, then separate the tocopherols from the rest of the vegetable oil using fractionation. It’s like distilling. The danger there is trace food allergens like soy and nut in tocopherol mixtures.

It’s also possible for chemists to create tocopherols without using plant matter. It’s commonly synthesized in three steps, using toxic petroleum-derived precursor chemicals—most significantly trimethylhydroquinone.

Hydroquinone is a controversial compound sold in the United States as a topical skin lightening agent. It’s used to get rid of dark spots or discolorations. The European Union has banned hydroquinone because of its potential carcinogenic effects. The FDA has expressed concern over the use of the compound but so far has not limited its sale in the United States. Inhaling residual hydroquinone aerosol from a cheap vitamin E oil would be problematic.

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Vitamin E oil has 8 forms

Eight main types of tocopherol exist, from alpha-tocopherol all the way through gamma-tocopherol.

“The most relevant vitamin E compound is alpha-tocopherol since it is the most abundant and potent of the group,” said Vu Lam, an official with Anresco Laboratories in San Francisco.

“The main difference between naturally occurring vitamin E and synthetic vitamin E is the presence of stereoisomers,” Lam explained. “Naturally occurring vitamin E will only contain the D-isomer (i.e. D-alpha-tocopherol). Synthetic vitamin E will typically be a mix of the D- and L–isomers (DL-alpha-tocopherol).”

Alpha-tocopherol is different than tocopheryl-acetate

“Tocopheryl-acetate is the ester form of tocopherol. Tocopheryl-acetate is more stable towards oxidation and will typically have longer shelf life than tocopherol,” Lam said.

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Neither is OK to inhale, experts say

All these chemicals with vitamin E activity go into foot creams, face creams, and other cosmetics as topicals. In some people it can cause rashes.

The cosmetics industry never considered tocopherols’ use for inhalation, at least beyond accidentally getting some lotion in your nose. Its acute inhalation toxicity is not known, and inhaling oil-like chemicals is generally a bad idea.

“Just the lack of toxicity data for inhaled Vitamin E acetate should raise red flags,” said Duke University School of Medicine Dr. Sven-Eric Jordt—expert on dangerous chemicals in vaping aerosol.

“It’s in every store in downtown LA.”
Alex Dixon, Floraplex CEO

“Lipids [i.e. oils] in the lung are highly toxic and have been associated with lung injury for years,” retired California pulmonologist Dr. Howard Mintz told Leafly. “They are most commonly seen in persons using ointments in their noses,” which can lead to a condition known as lipoid pneumonia.

All tocopherols may uniquely disrupt the function of the fluid lining the surface of the lungs.

“No vitamin E should be vaped regardless of its chemical structure,” said Eliana Golberstein Rubashkyn, a New Zealand–based pharmaceutical chemist and the chief scientist of Myriad Pharmaceuticals.

Drug-involved tocopherol inhalation injuries have been documented dating back at least to the year 2000.

Sickened lungs show up as cloudy on the left x-ray, and clear after treatment of one suspected VAPI patient in Utah. (Courtesy University of Utah)

Sickened lungs show up as cloudy on the left X-ray and clear after treatment of one suspected VAPI patient in Utah. (Courtesy University of Utah)

Tocopheryl-acetate may compound problems

The acetate form of vitamin E oil, tocopheryl-acetate, may worsen lung reactions.

Tocopherols adhere to your lung’s liner fluid, called lung surfactant. Lung surfactant enables oxygen to transfer from air into your body. Tocopherols serve to block the necessary gas transfer from occurring.

“Vitamin E has the ability to integrate on membranes by creating a coating over the pulmonary surfactant layer,” said Rubashkyn.

It’s part of a class of “long-chain” hydrocarbons that can adhere to and clump up your lung fluid, she said.

vape pen lung disease suspect Tocopheryl-acetate contains an acetate ring (arrow 1) that enhances its natural binding affinity (arrow 2) for lung fluid. (PubChem/Leafly)

Tocopheryl-acetate contains an acetate ring (arrow 1) that enhances its natural affinity for binding (arrow 2) to lung fluid. (PubChem/Leafly)

“Tocopheryl-acetate destabilizes the fragile, lipo-hydrophilic balance of this lung surfactant, causing occlusion, affecting the permeation of gases and substances in the bronchial structures and alveoli,” said Rubashkyn.

It’s like Saran-wrapping the inside of your lungs.

The result: Lung cells die. That damage can initiate a runaway immune system reaction resembling hypersensitivity pneumonitis, or immune checkpoint-inhibitor pneumonitis. This may especially occur with high doses of tocopheryl-acetate, such as in formulations found in a vape cart cut heavily with the oil. And it may occur even at relatively low vaping temperatures.

“Vitamin E acetate, when inhaled, is likely to accumulate at higher levels in the [lung immune cells],” said Dr. Jordt. “Vitamin E acetate may also oxidize or burn when heated too high in a vaping device, producing toxic chemicals in the vapor. Again, this is hypothetical but these are feasible mechanisms.”

Tocopheryl-acetate’s chemical acetate ring enables it to cling even more strongly to lung surfactant than the non-acetate form. It’s like Saran-wrapping the inside of your lungs.

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“Acetate or no acetate, the long chain that vitamin E has and its interactions with membrane surfaces is still considerable,” said Rubashkyn. “The acetate only makes vitamin E more lipophilic.”

Dumas de Rauly, chair of the ISO Committee on Vaping Standards and CEN Vaping Standards Committee, publicly criticized the use of vitamin E acetate in MJBizDaily. “In no case is this a product that you should be inhaling,” he said. “When you add products like vitamin E … when you add different kinds of lipid solvents to the mix, you’re making all of that oil stickier, and that stickiness is going to create these lung illnesses we’re seeing.”

“Inhalation of large amounts of lipids causes a natural immune response in the lung that tries to clear the chemicals but may also cause the complications we observe in patients,” said Dr. Jordt. “The lipids or hydrocarbons often accumulate in immune cells in the lung, the macrophages. These cells have an important job in the lung, eating up bacteria, viruses and toxic particles. However, if uncontrolled, they attack lung tissue and cause an exaggerated response.”

An oil-laden immune cell extracted from a VAPI patient in Utah (left). On the right, a normal macrophage. (Courtesy Andrew Hansen, Jordan Valley Medical Center)

Rare, oil-laden immune cells (macrophages) extracted from a VAPI patient in Utah (left). On the right, a normal macrophage. (Courtesy Andrew Hansen/Jordan Valley Medical Center)

Subsequent biopsies of lung tissue from 17 victims has broadened VAPI pathology beyond lipoid pneumonia to the more general term “chemical pneumonitis.” Mayo Clinic researchers state that, unlike lipid-laden macrophages, “foamy macrophages and pneumocyte vacuolization were seen in all cases”. Both findings indicate disruption of lung surfactant, and further implicate tocopherols.

Some merchants think it’s safe

Merchants have demonstrated inadequate proof of the product’s safety for inhalation.

Constant Therapeutics of California confirmed earlier this week that the company holds a patent on the use of alpha-tocopherol in a vape pen for medical cannabis patients.

Constance Finley, founder of Constance Therapeutics, said she developed it in consultation with an oncologist and has seen it used by more than 5,500 sick cancer patients.

“We do not have a single reported case of lung distress that has come to our attention,” said Finley.

Finley drew a clear distinction between the alpha-tocopherol her company uses and the tocopheryl-acetate found in some illicit vape cartridges, citing a 2013 New York Times article and one research paper showing differences in lung reaction to different tocopherols. Finley said she considers tocopheryl-acetate unsafe to use in any vape cartridges.

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Drew Jones, the founder of the Oregon-based vape cartridge additive maker Mr. Extractor, told Leafly over the weekend that tocopheryl-acetate was one of the ingredients in his company’s product Clear Cut. The company suspended sales of Clear Cut late last week.

Jones said he believed tocopheryl-acetate was safe based on its FDA safety sheet, which lists it as a nutrient. He also submitted to Leafly a commercial safety data sheet. While the safety sheet warned about inhalation, neither document specified anything about vaping, especially in high concentrations.

Jones also pointed to research studies of a different molecule in rats, a different molecule in 17 sheep, and 33 people who ate tocopheryl-acetate but did not inhale it as a high-temperature gas.

In stark contrast, 38 US children died from vitamin E oil injections in 1984. A follow-up study on pigs showed how high amounts of the oil trigger an immune response and can potentially cause death.

Tocopherols are rampant in the illicit market

Multiple industry operators told Leafly that vitamin E chemicals first appeared in vape pens on the illicit cannabis market in Los Angeles near the end of 2018, in a product called Honey Cut. Honey Cut Labs LLC of California is registered to Joshua Temple of Los Angeles. Honey Cut could be ordered through a website that was taken down shortly after Leafly identified it in a report last week.

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Honey Cut proved so popular as a THC oil cutting agent that dozens of knockoff versions appeared in early 2019 and soon began appearing in street-market vape cartridges nationwide.

Drew Jones estimated that more than 40 companies sold their own versions of a tocopheryl-acetate cutting agent. He estimated that it could be in up to 60% of US vape carts, up from almost none the year before. Alex Dixon, CEO of Floraplex, which makes the chemical thickener Uber Thick, told Leafly that as many as 50 million carts may contain the thickeners.

“It’s in every store in downtown LA,” said Jones. “Just about any [online sales] platform you can think of.”

vape pen lung disease suspect - New York officials said Uber Thick turned up nearly all tocopheryl-acetate. (Screengrab of YouTube video)

New York officials said Uber Thick turned up nearly all tocopheryl-acetate. (YouTube)

Vitamin E oil allowed in most legal markets

So far most of the vape carts seized in the ongoing investigation into the lung injuries have come from the illicit market. Stringent testing in state markets deters additive use—but doesn’t absolutely assure its absence. Regulations in legal adult-use cannabis markets do not explicitly ban many additives, including tocopherols. But they may soon. A number of state cannabis regulatory agencies have scrambled to get on top of the vape lung outbreak, and could be considering emergency new regulations in light of the health crisis.

Leafly freelancer Max Savage Levenson contributed to this report.

David Downs's Bio Image

David Downs

David Downs directs news and lifestyle coverage as the California Bureau Chief for Leafly.com. He's written for WIRED, Rolling Stone and Billboard, and is the former cannabis editor of the San Francisco Chronicle, as well as the author of several cannabis books including 'Marijuana Harvest' by Ed Rosenthal and David Downs. He co-hosts The Hash podcast. TW: @davidrdowns | IG @daviddowns

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  • GK

    The story seems to refer to this as only being a problem in “illicit” carts. So how can I tell if a cart I purchased from a legal shop contains Vitamin E acetate?

    • Anthony

      I would say if it doesn’t explicitly tell you what’s in it (Should be Propylene Glycol, Vegetable Glycerine, Nicotine, Flavorings) I’d stay clear of it. I’d recommend ditching the e-cigs and just get a box mod that you can refill with liquid from an e-juice vendor you trust. Plenty of local shops that mix their own stuff and tell you exactly what’s in it.

  • Jeebus Chocolo

    My freakin’ wife will not listen to me guys. She is still buying and smoking these black market vapes.

    • John Keller

      Destroy them when she is not paying attention. Help her find a trusted source of pure alternatives.

    • Laurie Matson

      She’s made her choice then. Not much you can do about it my friend.

    • MyNameIsTaken

      Honestly, I hope you never have to say, or even think, “I told you so.” anytime in the future.

      Why take a chance when there are so many other ways to get high?

    • Сергій Кабуд

      had a discussion with a friend on this. I was told a theory that it is a competitor’s disinformation covert operation: that there are no real cases, all the fake news bull. He vapes indeed

    • saynotohypocrisy

      I’d keep ragging her about it if I were you.

  • ben2talk

    What’s most annoying is the use of language to taint ‘vaping’ with a very limited case scenario and with Trump jumping on the fake news bandwagon and banning flavours which I don’t think have anything to do with this at all.

    Millions of people in the UK have been vaping for a very long time, where it’s accepted that it’s mor than 95% safer and recent investigations on the media have made it clear this is purely a focus on stupid American teens vaping oils to get high – not general vaping.

  • John Harvey

    Thanks for this article.I had tried them at the local mmj shop in philly. This is a few months ago. Now that it’s in the news, as I recall it made me feel like I was back in college, and the novelty of it all was oh so much fun! So I can’t say I was really testing it resolutely, b/c it was too much fun at the time to analyze anything more complicated than a light switch. They were pretty good but they were like $100 each. Too much for me. So I haven’t been using any lately. Glad to know about this. Thanks for getting the word out.

  • rspurgeon

    how can you find out if your vape cartridge has this stuff in it. I have Blue Dream, Mary Mechanix/

  • MyNameIsTaken

    The flavoring in e-juice is what is getting teenagers hooked on nicotine and probably should be illegal. These deaths are bringing vaping into the news mainstream, making our politicians take notice.

    • Chris Wiz

      okay but instead of a generation of kids on cigarettes there is kids using vapes for nicotine which is safer and less deadly.. still people are mixing the two issues.. the problem with the illness and death is from black market THC cartridges not flavored nicotine.. now if we want to solve the teenager epidemic its quite simple really… start tracking all bottles of flavored nicotine and when it ends up into a kids hand when they get busted they can track it right back to the person who bought it. That will stop people from buying flavors for kids by a tremendous rate, but out right banning them and forcing people like myself back to cigarettes is the worst possible option.

    • Chris Wiz

      I don’t care if they put the cigarette juice in an unmarked box with no label but to outright ban them all because kids vape nicotine is ridiculous there has to be some other kind of way to fix this problem. Besides what is banning flavors going to do to help all the people who are dying from smoking bad weed cartridges because it has nothing to do with vaping nicotine.

    • Treadingjello

      You truly believe the flavoring is what’s getting ‘kids hooked on nicotine’? By that logic, what was it when cigarettes were what kids did in the bathroom at school? Nicotine gets people hooked on nicotine, just as caffeine gets people hooked on caffeine, and alcohol gets people hooked on alcohol, because these substances are habit forming. Should we make all of those things illegal as well? How about this, we stop trying to make everything someone doesn’t like illegal without evidence that it should be, and enforce laws we have on the books for people that sell these products to underage buyers. Or even better, how about PARENTS start PARENTING, and actually pay attention to what their kids are doing, so that people like you don’t feel the need to have Daddy Government make things illegal to ‘protect the children’.

  • Cindy

    I purchased my vape cartridges from a licensed dispensary in November, 2018 (Massachusetts). I have used some this year that were shared by a friend, and I think the brand is one on the list to be concerned about (I told my friend). If I did inhale this in very small quantities, is there a chance it will work itself out of my lungs, or is any damage permanent?

    • saynotohypocrisy

      If the quantities are very small, I think the worst case scenario is a very small amount of damage. Good question about the ability of lungs to repair a small amount of damage, I don’t know the answer.

  • syrina gaston

    So is vitamin e in Vegetable glycerin? because I’ve seen many people making honey oil with that.

  • DaemonJax .

    Is the government is holding back on announcing the link between cannabis vape products and these lung illnesses because of fear of losing a potential source of (present or future) tax revenue in the form of cannabis product sales? It’s really strange that everything I hear and see is aimed at discouraging vaping in general, when the real problem is going to be oil-based additives that aren’t used in nicotine vape products.

    Even this article is guilty of this fear-mongering to some extent: “…Uber Thick, told Leafly that as many as 50 million carts may contain the thickeners.“It’s in every store in downtown LA,” said Jones. “Just about any [online sales] platform you can think of.”

    ^ Carts of what, exactly? Which stores in downtown LA? Which online sales platforms? You’re not going to find this crap in flavored ejuice containing nicotine. These oil-based additives simply can’t be cheaper than a propylene glycol + vegetable glycerin mixture. There’s no financial incentive to use them in any cartridge or juice meant for nicotine delivery.

  • Pand0ra

    I smoked about half of what I’m pretty sure was a contaminated cartridge right before my legal weed card came through, and have only smoked dispensary carts since then (about 2 months). I don’t feel sick but I’m worried I should go to a doc because I heard the vitamin e particles can’t clean out of the lungs on their own. Problem is I don’t have money for a doc, but I’m scared of damage to my lungs. Does anyone know if people who suspect they smoked a tainted cartridge are recommended to see a doc even if they don’t feel sick?