Nicorette, Commit lozenge and NicoDerm CQ cancer scares
Two new nicotine replacement therapy safety studies raise significant cancer concerns
Researchers have long known that NNN (N-Nitrosonornicotine) is a potent cancer causing chemical in animals. They know that nicotine is converted into nornicotine as tobacco ages, and that the curing and storage process somehow transforms nornicotine into the deadly carcinogen NNN. They know that additional NNN is created when tobacco is burned and inhaled by smokers. But imagine their horror upon discovering levels of NNN in the urine of nicotine gum and lozenge users that were 7, 31, 36 and 728 times higher than when smoking.
An October 2009 study published in the online version of Cancer Research found that urine NNN levels in 13 of 34 participants in two nicotine gum or lozenge studies were at times equal or greater than background urine NNN levels recorded while still smoking.
The below chart shows measurement of NNN in the urine of eight oral nicotine users in one portion of the study (POB data - see bottom of Table S1). Except for day 3, a week or more passed between urine samples. NNN's half-life inside the body is roughly three hours (184 minutes). NNN's three hour half-life means that within 24 hours more than than 99% of NNN can be eliminated from the body. Sampling urine just once in seven days, clearly, the below chart leaves gaping holes in our understanding of how high NNN spikes can actually rise and how frequently they occur.
|
Total NNN urine levels in 8 POB study subjects as measured in pmol/24h at both baseline while still
smoking and on specific days after quitting smoking while using oral nicotine (nicotine gum or lozenge)
|
| Gum or Lozenge User |
Baseline |
Day 3 |
Day 7 |
Day 14 |
Day 21 |
Day 28 |
Day 42 |
Day 56 |
| Oral NRT User #1 |
67 |
219 |
- |
256 |
622 |
578 |
253 |
130 |
| Oral NRT User #2 |
81.5 |
88 |
59,400 |
1,250 |
11 |
558 |
6.8 |
118 |
| Oral NRT User #3 |
15 |
3.9 |
0.3 |
0.2 |
0.3 |
473 |
0.3 |
0.2 |
| Oral NRT User #4 |
6.5 |
3.2 |
2.7 |
0.2 |
0.3 |
0.3 |
2.9 |
0.3 |
| Oral NRT User #5 |
329 |
14 |
359 |
32 |
16 |
14 |
18 |
3.7 |
| Oral NRT User #6 |
665 |
17,900 |
103 |
18,200 |
3,310 |
23,900 |
4,080 |
8.7 |
| Oral NRT User #7 |
8.7 |
64 |
1.4 |
0.5 |
0.07 |
0.06 |
.015 |
.016 |
| Oral NRT User #8 |
4.4 |
0.1 |
0.1 |
0.1 |
0.06 |
0.1 |
0.1 |
0.17 |
We've known for a decade that applying NNN twice weekly for 28 weeks inside the nasal cavity of three month-old minks required an average of 97 weeks before resulting cancerous tumors invaded the mink's brain (1999 Koppang). What we don't know after 25 years of nicotine gum being on the market is whether or not long-term use of nicotine replacement therapy (NRT) causes cancer.
NNN's primary path of harm in mice, rats and hamsters is development of cancer in the esophagus, trachea and nasal passages (1992 Kopping). But what about humans? Do massive NNN urine spikes suggest concerns about kidney or bladder cancer?
"In my opinion, the most likely cancers to be associated with long term NRT use would be lung and upper aero-digestive tract. But we do not have sufficient epidemiologic data on either" says Stephen S. Hecht, Ph.D, a University of Minnesota cancer prevention professor and researcher, and a co-author of the Cancer Research study.
The U.S. Food and Drug Administration (FDA) first approved prescription nicotine gum in 1984. Today, roughly 40% of Nicorette users are hooked on the cure. President Obama is believed to be among them. Why has it taken a quarter of a century for researchers to realize that NNN spikes in the urine of oral nicotine users can be up to 700 times higher than when smoking?
"Only relatively recently have we developed a method for measurement of NNN in human urine," says Professor Hecht.
Professor Hecht assisted Professor Irina Stepanov, also of the University of Minnesota, in developing a process for measuring tobacco nitrosamines, including NNN. They co-authored an April 2005 paper in Cancer Epidemiology, Biomarkers & Prevention. It found that the mean level of NNN in the urine of 14 smokers was 0.18 pmol/mg, while the level in 11 smokeless tobacco users was 3.5 times higher at 0.64.
But doesn't an NNN urine finding of 59,400 pmol over 24 hours mean that long-term use of oral forms of NRT is unsafe?
"I do not think there are sufficient studies to assess the effects of long term NRT use - safe or unsafe," says Professor Hecht. "NRT is safer than smoking because it does not involve exposure to multiple other toxicants and carcinogens. But our study raises some concerns about NRT use which should be addressed by the manufacturers of these products."
How does the human body transform nicotine into nornicotine and then NNN? Does the e-cigarette's nicotine vapor mist cause massive NNN urine spikes too, or like the transdermal nicotine patch (which the October study also evaluated), will spikes be far less frequent and vastly less profound? And why does the method of nicotine delivery affect NNN levels? We're left with vastly more questions than answers.
Nitrosation is a process of converting organic compounds into nitroso derivatives. According to Professor Hecht, "There are many factors which can influence nitrosation by generating relatively high levels of nitrite in the acidic environment of the stomach, together with nornicotine. These could include diet, infections, and others."
Still, today, we do not know which oral NRT users will experience massive NNN spikes, what causes them, how high the spikes will go, how frequently they'll occur, whether they will cause cancer, and if so, where in the body cancer will result.