Another repost from my old website. Hope you find it interesting!
In the interest of getting a better understanding of the endocrinology behind diabetes, I decided this afternoon to have a poke around the web at information on hormonal glucose regulation.
Type 1 diabetes is fundamentally a disorder of glucose regulation related to the body’s inability to produce insulin. The cells of the body that produce insulin are located in the pancreas in the regions known as the “islets of Langerhans” . In type-1 diabetes, these insulin-producing cells (beta-cells) are destroyed due to an autoimmune response resulting in a dramatic reduction or elimination of the body’s production of insulin.
Since there are a number of glucoregulatory hormones which increase blood glucose levels (including one produced in alpha-cells of the pancreas called glucagon), the absence of insulin leads to a state of hyperglycaemia if untreated. Chronically high levels of glucose in the bloodstream can lead to a number of complications. A lack of insulin in the bloodstream can also lead to diabetic ketoacidosis. Ketoacidosis means the pH level of the blood falls below its normal range due to the acidic effect of ketone bodies in the bloodstream. The reason for the presence of ketone bodies in the bloodstream is related to the body’s mechanisms for handling starvation. Continue reading “hormones and type 1 diabetes”
I used to post a bunch of interesting stuff on slightlyodd.com on my old content management system. Sadly, my webhost died and I lost a bunch of articles. However! Thanks to the magic of the internet wayback machine on archive.org, I can repost these articles again! So here we go – the first one on paracetamol poisoning.
During my hours of productive work today, I noticed an article on smh.com.au about the death of a 33 year-old woman to paracetamol poisoning. I briefly considered how tragic this was but in typical fashion soon began wondering about the medical mechanism of paracetamol poisoning. I’d heard that it’s a particularly gruesome kind of death involving liver failure but wasn’t sure of the details. Off to the net I went!
A tiny bit of background (though you’re probably already quite familiar with paracetamol). Also known as acetaminophen, paracetamol is a condensed name derived from para-acetyl-amino-phenol. It’s an analgesic (painkiller) and antipyretic (used for fever relief). Unlike aspirin or ibuprofen, paracetamol is not an anti-inflammatory drug and is therefore more gentle on the stomach. In therapeutic doses, it is among the safest analgesics in use however the therapeutic dose is quite close to the toxic dose. A typical dose consists of 1 gram, taken no closer than 4 hours apart. Packaging usually recommends against consumption of more than 8 tablets in a 24 hour period.
Continue reading “paracetamol poisoning”
Not content to leave methanol without drawing some theoretical conclusions, here’s the last I have to say on the topic.
- Blood’s buffering capacity is around 38.5 mEq/L/pH at physiological pH levels, and is more capable of buffering in an acidic than an alkaline direction.
- 1 mEq of formic acid is 46 milligrams.
- Acidosis is clinically defined as a drop in blood pH below 7.35 (Edit: I forgot to mention, blood’s usual pH is 7.4). By those numbers above, I figure it would take about 88 milligrams of formic acid to reduce the pH of a litre of blood by this amount – remember, you’ve got around 5 litres of blood. You’d have to have over 20 times as much formic acid as is produced by the consumption of one can of artificially sweetened soft-drink. That’s a pretty big margin of safety right there. I mean, as that professor in the document I linked below says, toxicity is all about the dose.
“The adage among toxicologists is “the dose makes the poison”–vitamin
A, iron, and selenium, to name a few, are required by the body but are
toxic at too-high levels.”
So – unless someone can show how methanol harms humans in some way unrelated to the production of formic acid, I’m pretty satisfied this particular metabolic byproduct of aspartame is safe. This is consistent with empirical studies. Next, the other two! Well later, anyway. Feel free to tear down my logic or chemistry in the meantime. It’s been a loooong time since I’ve tried to figure out some of this stuff.
Blood is a pH buffered solution, and the average adult has around 5 liters of it. A standard can of diet coke has approximately 200mg of aspartame, 10% of which is metabolised to methanol. That 20mg of methanol is metabolised rapidly by alcohol dehydrogenase into formaldehyde. This formaldehyde is then rapidly metabolised into formic acid via formaldehyde dehydrogenase – alcohol dehydrogenase is the rate limiting step in this process. By and large, the pathological effects of methanol are related to metabolic acidosis (a drop in blood pH) from build-up of formic acid.
I’ve been messing around with the chemistry for an hour or so, but am way too out of practice to write anything sensible about it. So for now, I’m going to go with the following bits and pieces I’ve found out:
- The lowest recorded fatal dose of methanol is 6 grams. That’s 300 times the amount of methanol produced by the metabolism of one can’s worth of aspartame.
- Methanol is metabolised with a half-life of around 1.5 to 2 hours in humans at levels found in artifically sweetened drinks, fruit juices and red wine.
- A glass of tomato juice contains enough pectin to produce approximately 85mg of methanol during metabolism – as compared to apple juice (21mg) and diet coke (20mg).
Draw whatever conclusions you like from that. Perhaps when I’ve got a bit more free time I might have another stab at calculating the ability of blood to buffer the formic acid. If you feel like having a stab, here’s a journal article outlining the buffering capacity of human blood.
Oh and check out this article too, on aspartame metabolism relating directly to methanol production.
I drink quite a bit of diet coke. Probably two cans, each day that I work. I’m forever being told by people “that’ll give you brain cancer you know” or “that stuff’s gonna kill you!”
I admit, it’s not the best habit to be drinking some kind of synthetic beverage a couple of times a day. It’d probably be more healthy if I drank water instead. However, water doesn’t taste fizzy and delicious so I choose the browner, tastier option. There are several fronts on which people base their concern but certainly the most adamant opposition is due to the use of aspartame as an artificial sweetner. Here’s a quote from the FDA in 1999: “[aspartame is] one of the most thoroughly tested and studied food additives the agency has ever approved.” Just putting that out there, to begin with.
Over the next little while, I’m going to try and bust up some myths using a collection of theoretical biochemistry and citation of empirical studies. I want to debunk the toxicity of each of the first-order metabolic products of aspartame – methanol, phenylalanine and aspartic acid.
I’ve half-written and half-researched methanol thus far. I intend not only to quote the numerous studies and facts everyone else does, but also to show theoretically that the amount of methanol produced from the metabolism of aspartame is far from enough to overcome the blood’s various pH buffering mechanisms. It is metabolic acidosis which leads to the typical symptoms of methanol poisoning.
If I’m not bored after debunking aspartame, I’ll treat you to a couple of other debunkings I’ve come across – like the one about how caffeinated beverages dehydrate you.
Stay tuned! I’m on my little high-horse!
I’m pleased to report that it’s iron containing enzymes like myeloperoxidase that ensure that the colour of the stuff that comes out of your chest and head while sick is a charming green. Present in neutrophils (a type of white blood cell), this enzyme will convert hydrogen peroxide and free chloride ions into hypochlorus acid – not too dissimilar to what you use to clean your bathroom floor.
Sadly, spewing bleach all over the place tends to kill neutrophils, sending their proteiny remains out into your tissue to brighten your day. These are the things I think about when I cough up goo.