Booze Still Glamorized Despite The Strong Alcohol-Cancer Connection

Alcohol is categorized as a class 1 cancer-causing substance. Although the IARC classification doesn’t imply that alcohol is as dangerous as other proven human carcinogens such as benzene and heavy cigarette smoking, the findings should not be overlooked. This is especially true with regard to certain types of cancers and considering that: (1) drinking alcohol is even riskier for women and (2) social attitudes regarding alcohol continue to be extremely permissive, and no cancer warnings exist on any product labels.  As is the case with all carcinogens, the risk tends to increase with the overall amount of ethanol consumed. But the danger-threshold has recently become much lower based on current research.

When I first looked into the alcohol-cancer connection, 11 years ago,  Dr. Rachel Thompson, Science Programme Manager at the WCRF (World Cancer Research Fund) had said ,  “If you are drinking a pint of lager or a large glass of wine everyday, then this might not seem like a lot.” She further added, “But the science shows you are increasing your risk of bowel cancer by 18 percent and your risk of liver cancer by 20 percent.”

One serving (12 fluid oz of beer or 5 fluid oz of wine, or 1.5 fluid oz of 80-proof distilled spirits) contains 14 grams of pure ethanol, the type of alcohol in drinks. The data of the 2012 meta study, which Rachel Thompson referred to, was only available for an average consumption of 25, 50 and 100 g/day, which amounted to approximately 1.5, 3 and 6 drinks a day, respectively.

According to the latest data available in 2023 which has caused recommended guidelines to become more strict, one drink per day for a woman increases the risk of liver cancer by 6.1% but that of cirrhosis by 255%; esophageal cancer by 21.9%; of cancer of the oral cavity and pharynx by 61.4%; breast cancer 14.7%. Even at only 5 grams per day, equivalent to only 2.5 drinks per week, the elevated risks are still not negligible: 

One drink per day for a male increases the risk of colorectal cancer by 10.7%; esophageal cancer by 21.9%; cancer of the larynx by 24%. Those numbers spike significantly when the dose doubles. At 2.5 drinks per week for males, the increased risk dips below 10% for those cancers, except for oral and pharynx cancers, which get elevated by 13.1%, just as they do for women.

Statistics aside, how does ethanol induce cancers? No clear mechanism has been elucidated but there are many plausible scenarios, according to a 2006 review paper in the Lancet. Acetaldehyde (pictured on the right), which is alcohol’s main metabolite, is genotoxic, especially in genetically susceptible individuals where the acetaldehyde is not as quickly oxidized to the innocuous acetate. There is at least in vitro evidence that acetaldehyde and not alcohol itself does genetic damage in the liver, head, neck and breast. Ethanol also increases estrogen concentration, and it acts as a solvent for tobacco’s carcinogens.

In general why are women even more sensitive to alcohol than men? It is due a number of factors: smaller body size increases the concentration. A higher body fat/water ratio retains more alcohol due to alcohol’s high solubility in fat. Hormonal effects are important too. Finally, women produce smaller quantities of the enzyme alcohol dehydrogenase (ADH), which is released in the liver and breaks down alcohol in the body.

Sources:

CCSA-LRDG-Update-of-Canada’s-LRDG-Final-report

Meta Study: http://pubs.niaaa.nih.gov/publications/arh25-4/263-270.htm

Review Paper of Possible Mechanisms


 http://www.omniameeting.com/filereviews/Cortese%20Review.pdf

http://www.ncbi.nlm.nih.gov/pubmed/7895211

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1646951/

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The False Morel Mushroom: Intriguing Chemistry and Biological Mimicry.

The false morel, Gyromitra esculenta

False morels are mushrooms that look like morels but which contain a toxin. One of the species, Gyromitra esculenta, for example, is a false morel that is apparently delicious. But if it’s not cooked properly, it can lead to vomiting and diarrhea. On occasion it could even kill consumers by affecting the heart, given that its poison affects nerves which control muscle coordination.

The first problematic compound is gyromitrin, named after the genus of Gyromitra esculenta. There are several reasons why the effects of eating the false morel vary so much, from having no effect to being mortal. For starters, the amount of the toxin can vary greatly from one mushroom to the other. The amount of gyromitrin in false morels can lie anywhere between 40 to 732 milligrams per kilogram of mushrooms (wet weight). Technically, gyromitrin isn’t poisonous in itself until it gets broken down in the stomach into acetaldehyde & monomethylhydrazine(MMH). Presumably not everyone metabolizes it the same way. But when enough MMH is formed, that compound, which coincidentally is a a rocket propellant that spontaneously ignites when it comes into contact with an oxidizer like N₂O₄, reduces pyridoxine and makes it ineffective. That’s a problem because pyridoxine is a form of Vitamin B6, which among other things, is needed to make neurotransmitters. That explains the poison’s ability to stop the heart.

Monomethylhydrazine. Each blue sphere represents a nitrogen atom; grey, carbon and white, hydrogen.
gyromitrin

 

In the 1950s, US pediatricians observed cases of an unusual seizure disorder in young infants. The usual anticonvulsants did nothing to abate the symptoms, but there was a dramatic improvement when vitamin B6 was given to them. Eventually, someone figured out that the babies affected were fed a commercial formula that contained only one-third the vitamin B6 found in other baby formulas. A manufacturing process reduced the pyridoxine content of the synthetic milk, just like mushroom-derived MMH does.

The toxic false morel, Gyromitra esculenta, and an edible true morel mushroom. Source: Wikipedia.

How one prepares the mushrooms also makes an immense difference to how toxic false morels can be. Airdrying is a good preliminary treatment, as that in itself destroys some toxin.  The bulk of the poison is then destroyed by heating. The ‘safest’ way to prepare Gyromitra species is to boil the mushrooms a couple of times (being careful not to inhale any of the vapors, which could contain the volatile toxin). The cooking water has to be thrown out, and then the mushrooms are to be fried in a separate pan. This removes the majority of the monomethylhydrazine.

In the early stages of growth, the true morel not only has the characteristic cavities, brain-like texture and color of the false morel, but it is also more spherical in shape, like its “impostor”. Is it an interesting example of Batesian mimicry, in which an organism, which is not poisonous, has evolved the appearance similar to those of non-poisonous species? The organism without the poison enjoys the benefits of carrying a poison and avoids being eaten but without having to invest the metabolic energy it takes to produce the poison.

Batesian mimicry: on the left is the non-poisonous mimic  Papilio polytes, which resembles the unpalatable Pachliopta aristolochiae (right). Source: Wikipedia

Several sources point out that “this mushroom is still consumed, despite its known carcinogenic properties”. But IARC has classified it as a group 3 carcinogen since 1987, which means that although it has shown some carcinogenic tendencies in some animals, there is no evidence that it causes cancer in humans. It’s best to focus on how to cook them, if one insists on eating them.

Other Sources:

Deficiency Diseases of the Nervous System Joseph Jankovic MD, in Bradley and Daroff’s Neurology in Clinical Practice, 2022

Journal of Chromatography A, 1125 (2006) 229–233. Mehrdad Arshadi and al.  Gas chromatography–mass spectrometry determination of the pentafluorobenzoyl derivative of methylhydrazine in false morel
(Gyromitra esculenta) as a monitor for the content of the toxin gyromitrin

An Isolated Plant Family

There is a family within the angiosperms (flowering plants) that, from an evolutionary viewpoint, is relatively isolated. The only family that’s somewhat closely related to it is that of the morning glory, Convolvulacea. The family in question has about 1700 species, which is not much compared to the diversity within the pea, orchid and sunflower families, which all together account for over 60 000 species or roughly 20% of all flowering plants.

Its flowers are very often star-shaped with 5 sepals, 5 petals and 5 stamens, and its stems and leaves host a variety of both toxic and useful alkaloids. If you haven’t guessed it yet we are referring to the Solanaceae family, whose most familiar members include tomatoes, eggplants, tobacco, potatoes, petunias, jimson weed and deadly nightshade (belladonna). Not many people realize that the tomato, has a close relative known as the tamarillo or tree tomato, also a native of the Andes. This shrub produces fruits of various colors, with the orange one being sweeter than the red. Currently, the tomato and tamarillo are classified in different genera, but that grouping is probably mistaken according to DNA studies.

On the left are representatives of a couple of tomato varieties from my garden. On the right is a tree tomato, which like its relative is also originally from the Andes.

What kind of alkaloids are found in Solanaceae plants? Potatoes and tomatoes both contain solanine, which has fungicidal and insect-repellent properties. Tomatine in tomatoes serves the same purpose and is also present in unripe tomatoes. If you touch the stems or leaves of tomatoes while picking them, you will cause their tiny hairs (trichomes) to release alkaloids along with oils, which give plants their distinctive scent. Unfortunately, some people are very sensitive to some of the compounds made by the trichomes, and they develop eczema: itchy skin with small, fluid-filled bumps leading to scaly skin from the release of histamines by the immune system.

Other Solanaceae alkaloids go far back in history and have proven to be beneficial. Over 3000 years ago, Egyptians added extracts of a Solanaceae family-member known as mandrake to their beer. Mandrake contains atropine, scopolamine and hyoscyamine, which block the action of the neurotransmitter acetylcholine. The trio of alkaloids, which are also found in jimson weed, belladonna and henbane, can cause hallucinations, but individually, at the right dose and for the right condition, each can serve as a useful drug. Their similar structures can be seen below. Atropine and hyoscyamine (left and top right) are mirror images of one another but not identical in the way that a right handed glove is not the same as a left handed one. Scopolamine differs in having an epoxide ring (triangular arrangement of two carbons and an oxygen) adjacent to the nitrogen ring.

Atropine can be used to dilate eyes, to treat a specific type of heart block and to treat certain cases of organophosphate poisoning. Scopolamine, in the form of a transdermal patch, is used to prevent nausea and vomiting after anesthesia or from narcotic pain medicines, and it’s also good for motion sickness. Hyoscyamine works by decreasing acid-production in the stomach, slowing down the natural movements of the gut and relaxing muscles in many organs, which is why it is used for irritable bowel syndrome and cramps. In Australia, indigenous people have exploited their continent’s Solanaceae’s Duboisia plants (corkwood) for centuries. These plants are also a source of scopolamine and hyoscyamine. The structure of the natural alkaloids has also inspired synthetic derivatives such as benzatropine, which is used to counteract the side effects of antipsychotic drugs and also for Parkinson’s disease.

Benzatropine is a synthetic analogue of atropine. It’s used to counteract dystonia, a side effect of prolonged use of many antipsychotic drugs.

Since atropine, scopolamine and hyoscyamine can easily be absorbed through the skin, it has been told that the flying ointment of underwear-less witches was rubbed on broomsticks, allowing their exposed rectums and vaginas to serve as absorption sites for the drugs. It’s the basis for the notion that witches “flew”— in reality hallucinating—on their broomsticks. When I first heard that story in my youth, I became forever interested in the combination of botany and chemistry!

Sources:

The Botanical Garden. Roger Phillips and Martin Ryx. 2002

Tomato Glycoalkaloids:  Role in the Plant and in the Diet. J. Agric. Food Chem. 2002, 50, 21, 5751–5780

Tropane Alkaloids: Chemistry, Pharmacology, Biosynthesis and Production. Molecules. 2019 Feb; 24(4): 796

Structures from Chemspider.com