What’s the news on sucralose?

These past days the press has been abuzz with frightening tales:

• This Common Artificial Sweetener Can Break Down DNA, Scientists Warn
• Sucralose Damages DNA, Linked to Leaky Gut
• Chemical found in common sweetener damages DNA
• Chemical found in widely used sweetener breaks up DNA
• Chemical from Splenda breaks up DNA

How true and/or serious is this?

Firstly, let’s manage expectations. Pineapple juice also breaks down DNA, but is not generally considered a health risk. So let’s keep that in mind, while we look into the science.

Is sucralose as scary as pineapple juice, or is it something actually dangerous?

The new study (that sparked off these headlines)

The much-referenced study is publicly available to read in full—here it is:

Toxicological and pharmacokinetic properties of sucralose-6-acetate and its parent sucralose: in vitro screening assays

You may notice that this doesn’t have quite the snappy punchiness of some of the headlines, but let’s break this down, if you’ll pardon the turn of phrase:

• Toxicological: pertaining to whether or not it has toxic qualities
• Pharmacokinetic: the science of asking, of chemicals in bodies, “where did it come from; where did it go; what could it do there; what can we know?”
• Sucralose-6-acetate: an impurity that can be found in sucralose. For perspective, the study found that the sucralose in Splenda contained “up to” 0.67% sucralose-6-acetate.
• Sucralose: a modified form of sucrose, that makes it hundreds of times sweeter, and non-caloric because the body cannot break it down so it’s treated as a dietary fiber and just passes through
• In vitro: things are happening in petri dishes, not in animals (human or otherwise), which would be called “in vivo”
• Screening assays: “we set up a very closed-parameters chemical test, to see what happens when we add this to this” ⇽ oversimplification, but this is the basic format of a screening assay

Great, now we understand the title, but what about the study?

Researchers looked primarily at the effects of sucralose-6-acetate and sucralose (together and separately) on epithelial cells (these are very simple cells that are easy to study; conveniently, they are also most of what makes up our intestinal walls). For this, they used a fancy way of replicating human intestinal walls, that’s actually quite fascinating but beyond the scope of today’s newsletter. Suffice it to say: it’s quite good, and/but has its limitations too. They also looked at some in vivo rat studies.

What they found was…

Based on samples from the rat feces (somehow this didn’t make it into the headlines), it appears that sucralose may be acetylated in the intestines. What that means is that we, if we are like the rats (definitely not a given, but a reasonable hypothesis), might convert up to 10% of sucralose into sucralose-6-acetate inside us. Iff we do, the next part of the findings become more serious.

Based on the in vitro simulations, both sucralose and sucralose-6-acetate reduced intestinal barrier integrity at least a little, but sucralose-6-acetate was the kicker when it came to most of the effects—at least, so we (reasonably!) suppose.

Basically, there’s a lot of supposition going on here but the suppositions are reasonable. That’s how science works; there’s usually little we can know for sure from a single study; it’s when more studies roll in that we start to get a more complete picture.

What was sucralose-6-acetate found to do? It increased the expression of genes associated with inflammation, oxidative stress, and cancer (granted those three things generally go together). So that’s a “this probably has this end result” supposition.

More concretely, and which most of the headlines latched onto, it was found (in vitro) to induce cytogenic damage, specifically, of the clastogenic variety (produces DNA strand breaks—so this is different than pineapple’s bromelain and DNA-helicase’s relatively harmless unzipping of genes).

The dose makes the poison

So, how much is too much and is that 0.67% something to worry about?

• Remembering the rat study, it may be more like 10% once our intestines have done their thing. Iff we’re like rats.
• But, even if it’s only 0.67%, this will still be above the “threshold of toxicological concern for genotoxicity”, of 0.15µg/person/day.
• On the other hand, the fact that these were in vitro studies is a serious limitation.
• Sometimes something is very dangerous in vitro, because it’s being put directly onto cells, whereas in vivo we may have mechanisms for dealing with that.

We won’t know for sure until we get in vivo studies in human subjects, and that may not happen any time soon, if ever, depending on the technical limitations and ethical considerations that sometimes preclude doing certain studies in humans.

Bottom line:

• The headlines are written to be scary, but aren’t wrong; their claims are fundamentally true
• What that means for us as actual humans may not be the same, however; we don’t know yet
• For now, it is probably reasonable to avoid sucralose just in case

All About Cholesterol

When it comes to cholesterol, the most common lay understanding (especially under a certain age) is “it’s bad”.

A more informed view (and more common after a certain age) is “LDL cholesterol is bad; HDL cholesterol is good”.

A more nuanced view is “LDL cholesterol is established as significantly associated with (and almost certainly a causal factor of) atherosclerotic cardiovascular disease and related mortality in men; in women it is less strongly associated and may or may not be a causal factor”

You can read more about that here:

Statins: His & Hers? ← we highly recommend reading this, especially if you are a woman and/or considering/taking statins. To be clear, we’re not saying “don’t take statins!”, because they might be the right medical choice for you and we’re not your doctors. But we are saying: here’s something to at least know about and consider.

Beyond HDL & LDL

There is also VLDL cholesterol, which as you might have guessed, stands for “very low-density lipoprotein”. It has a high, unhealthy triglyceride content, and it increases atherosclerotic plaque. In other words, it hardens your arteries more quickly.

The term “hardening the arteries” is an insufficient descriptor of what’s happening though, because while yes it is hardening the arteries, it’s also narrowing them. Because minerals and detritus passing through in the blood (the latter sounds bad, but there is supposed to be detritus passing through in the blood; it’s got to get out of the body somehow, and it’s off to get filtered and excreted) get stuck in the cholesterol (which itself is a waxy substance, by the way) and before you know it, those minerals and other things have become a solid part of the interior of your artery wall, like a little plastering team came and slapped plaster on the inside of the walls, then when it hardened, slapped more plaster on, and so on. Macrophages (normally the body’s best interior clean-up team) can’t eat things much bigger than themselves, so that means they can’t tackle the build-up of plaque.

Impact on the heart

Narrower less flexible arteries means very poor circulation, which means that organs can start having problems, which obviously includes your heart itself as it is not only having to do a harder job to keep the blood circulating through the narrower blood vessels, but also, it is not immune to also being starved of oxygen and nutrients along with the rest of the body when the circulation isn’t good enough. It’s a catch 22.

What if LDL is low and someone is getting heart disease anyway?

That’s often a case of apolipoprotein B, and unlike lipoprotein A, which is bound to LDL so usually* isn’t a problem if LDL is in “safe” ranges, Apo-B can more often cause problems even when LDL is low. Neither of these are tested for in most standard cholesterol tests by the way, so you might have to ask for them.

*Some people, around 1 in 20 people, have hereditary extra risk factors for this.

What to do about it?

Well, get those lipids tests! Including asking for the LpA and Apo-B tests, especially if you have a history of heart disease in your family, or otherwise know you have a genetic risk factor.

With or without extra genetic risks, it’s good to get lipids tests done annually from 40 onwards (earlier, if you have extra risk factors).

See also: Understanding your cholesterol numbers

Wondering whether you have an increased genetic risk or not?

Genetic Testing: Health Benefits & Methods ← we think this is worth doing; it’s a “one-off test tells many useful things”. Usually done from a saliva sample, but some companies arrange a blood draw instead. Cost is usually quite affordable; do shop around, though.

Additionally, talk to your pharmacist to check whether any of your meds have contraindications or interactions you should be aware of in this regard. Pharmacists usually know contraindications/interactions stuff better than doctors, and/but unlike doctors, they don’t have social pressure on them to know everything, which means that if they’re not sure, instead of just guessing and reassuring you in a confident voice, they’ll actually check.

Lastly, shocking nobody, all the usual lifestyle medicine advice applies here, especially get plenty of moderate exercise and eat a good diet, preferably mostly if not entirely plant-based, and go easy on the saturated fat.

Note: while a vegan diet contains zero dietary cholesterol (because plants don’t make it), vegans can still get unhealthy blood lipid levels, because we are animals and—like most animals—our body is perfectly capable of making its own cholesterol (indeed, we do need some cholesterol to function), and it can make its own in the wrong balance, if for example we go too heavy on certain kinds of (yes, even some plant-based) saturated fat.

Read more: Can Saturated Fats Be Healthy? ← see for example how palm oil and coconut oil are both plant-based, and both high in saturated fat, but palm oil’s is heart-unhealthy on balance, while coconut oil’s is heart-healthy on balance (in moderation).

Want to know more about your personal risk?

Try the American College of Cardiology’s ASCVD risk estimator (it’s free)

Take care!