• Cryophilia@lemmy.world
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    15 days ago

    So far we’ve talked about two of the 3 categories, non-profits and government agencies, both of whom say “nicotine bad” with no supporting data at all. So let’s get to the 3rd category: the actual fucking data.

    Let’s look at one of the top results, from the NIH. The introduction starts with the sentence “Tobacco is the leading cause of preventable cancers.” Oof, not a good sign. But let’s continue.

    Nicotine is well known to have serious systemic side effects in addition to being highly addictive. It adversely affects the heart, reproductive system, lung, kidney etc. Many studies have consistently demonstrated its carcinogenic potential.

    Oh yeah? Let’s look at these studies.

    Jensen et al, “Mechanisms for nicotine in the development and progression of gastrointestinal cancers”. This is another “study of studies”. Note we’re two layers deep here and still haven’t seen the actual data. The Jensen study focuses on the mechanisms that nicotine can cause cancer, but doesn’t disclose the crucial data about dosage and likelihood. But it does reference other studies. Let’s go deeper. .

    1a) Tun et al, “Tobacco use and cancer: an epidemiologic perspective for geneticists”. The Jensen article claims, “There is increasing evidence that nicotine and its derivatives activate and promote key processes in the carcinogenesis of GI cancers.” and references the Tun study. The Tun study states in the Abstract:

    This review considers: (a) the epidemiology of tobacco use; (b) cancers presently classified as smoking-attributable by the US Surgeon General; © the magnitude of the epidemic of cancers and other diseases caused by tobacco use; (d) selected issues in the epidemiology of lung cancer; and (e) the interface of genetics and epidemiology in understanding, preventing, and treating tobacco-attributable disease.

    FUCKING TOBACCO, NOT NICOTINE. AGAIN.

    1b) In the section “Role of nicotine in esophageal and oral cancer”, the Jensen study references several different studies.

    1b1)Arredondo et al, “A Receptor-Mediated Mechanism of Nicotine Toxicity in Oral Keratinocytes”: studied possible carcinogenic effects on the skin, mouth, and digestive tract. Studied by incubating human cells in a culture of nicotine, and also by exposing rats to a constant exposure of pure nicotine in water (as well as a different group exposed to cigarette smoke). This is a constant, 24/7 exposure to the equivalent level of nicotine from secondhand smoke from 1 cigarette / 8 minutes for three weeks. As the Materials and Methods section says, “This concentration of sidestream cigarette smoke was selected because it represents a high ambient level that individuals could encounter at home or in other settings where smoking occurs”. It’s a study that tests the secondhand smoke affects of ambient nicotine. The incubated cells were exposed to “10 μM of pure Nic” which is the equivalent of each tiny little cell culture puffing on two cigarettes (10 kilamoles = 1.6224 mg of nic, average cigarette contains about 8.4 mg of nic, source) Best data I can find is that a pack-a-day smoker and a high-concentrate vape user consume about the same levels of nicotine as each other. But vape clouds produce almost undetectable amounts of “secondhand nicotine”, so it’s not directly comparable. The rats who drank the pure nicotine also were given doses of 10 μM (again, equal to about 2 cigarettes worth) constantly for 3 weeks.

    Basically, way more nicotine than the typical vaper will encounter, only generates some indicators for some cells to possibly malform. It’s demonstration that at extremely high concentrations, nicotine can generate a mechanism for cancer.

    1b2) Zong et al, “Nicotine enhances migration and invasion of human esophageal squamous carcinoma cells which is inhibited by nimesulide”: treats cells with 10x-20x the concentration of nicotine as above. Not even worth considering in the context of vaping. It’s a proof-of-concept study to show that nicotine at some level can have these effects, trusting to future studies to dial it in to levels commensurate with smoking/vaping.

    1b3) Nguyen et al, “Choline Acetyltransferase, Acetylcholinesterase, and Nicotinic Acetylcholine Receptors of Human Gingival and Esophageal Epithelia”: paywalled, couldn’t bypass. Appears to be similar study as 1b1 but observing different reactions. No word on dosage in abstract.

    1c) Discusses gastric cancer. Most of these studies are too paywalled.

    1c1) Yang et al, “The role of TNF genetic variants and the interaction with cigarette smoking for gastric cancer risk: a nested case-control study”.: exclusively studies cigarette smoking.

    1c2) Kita et al, “Expression of uPAR mRNA in peripheral blood is a favourite marker for metastasis in gastric cancer cases”: this study doesn’t directly deal with nicotine, but with a certain marker whose prevalence could help metastasize gastric cancers. The reasoning of the Jensen study is that since nicotine increases the prevalence of this marker, nicotine use could contribute to carcinogenic effects. (funny enough the Jensen study then cites another paywalled study whose abstract, at least, does not even mention this particular marker)

    1d) Discusses colon cancer.

    1d1) Wong et al, “Nicotine promotes cell proliferation via α7-nicotinic acetylcholine receptor and catecholamine-synthesizing enzymes-mediated pathway in human colon adenocarcinoma HT-29 cells”: also geared towards cigarette smokers, but investigates nicotine independently. Mostly paywalled, with snippets available. One of the snippets references a dose of 1 μM stimulating adrenaline production, which can lead to increased cancer risk. 1 μM is a significant enough dose for regular vape users, but it’s still several steps removed (nicotine can increase adrenaline, adrenaline can increase cancer risk). Unfortunately, the methods and details part is all paywalled.

    1d2) Wong et al (same Wong), “Nicotine Promotes Colon Tumor Growth and Angiogenesis through β-Adrenergic Activation”: similar line of investigation. Mice were implanted with tumors, and then fed nicotine-laden water at different concentrations. More nicotine --> more adrenaline --> bigger tumors. Note: the amount of nicotine used was supposedly consistent with previous studies showing concentrations of nicotine in typical smokers, but since mice drink about 5.8 ml of water a day and these guys were delivering either 50 or 200 mg of nicotine per ml, that’s 290 or 1160 mg of nicotine–the equivalent of either six or 24 cigarettes per day…FOR A MOUSE. In fact, the study they linked to support their claim that they’re using levels of nicotine consistent with typical smokers, while paywalled, has an excellent abstract stating that a nicotine patch of 44 mg a DAY was equivalent to the nicotine consumption of a >30 cigs/day smoker. That’s a lot lower than the 8.4mg noted in my source above in 1b1, which should suggest 252 mg of nicotine, but either way, it’s an absurd dose to give to a mouse.

    So like, they took the high end of that study they referenced, increased it a little, used that as the low end of their study, made their high end 4 times that, and then gave that amount to a fucking mouse injected with a human tumor. And then did it again, 5 more times a day. And then said that “mimicked the daily intakes of cigarettes in smokers”. HAH.

    1e) Pancreatic cancer. Most of this deals with models and potential modes of carcinogenity from nicotine, not hard data. But we can breadcrumb our way from the models to actual studies.

    1e1) The Jensen study cites this Chowdhury study which cites, amusingly enough, one of those non-sourced government proclamations from my last post, as well as “Unpublished studies from our laboratory”. Their model is convincing enough: nicotine activates certain signaling pathways which starts a cascade effect causing out of control cell proliferation (aka cancer). But the first domino in that chain is literally “trust me, bro” with no published experimental data.

    Side note: see how incestuous this all is? We have a study of studies (NIH) referencing a study of studies (Jensen) referencing a study of studies (Chowdhury), referencing…nothing at all. It’s actually weirdly analogous to cancer itself, or maybe I’m just seeing cancer everywhere by now.

    1f) liver cancer. This section admits “there is limited information” and has to resort to using the old “smoking/nicotine” trick.

    I told you this shit requires a lot of digging. The NIH study-of-studies has 8 different papers it references, just in the “nicotine causes cancer” section. It’s a lot of work to wade through.