Latest / Common Sense Health / Is Lp(a) Actually Dangerous? The Missing Context
Transcript
- Stephen Thomas BSc. Hons: Hello? Let's talk about LP little a, know, the underdog lipoprotein that somehow gets blamed for everything, you know, like a wasp or a barbecue. Now, during consultations, if it pops up on a blood test, people start freaking out immediately and they just go into a panic. And yet at the very same time, you will also hear a totally different camp saying careful lowering LP little a might increase your risk of other things. And that's usually based on a study I will cover very shortly. So rather than do the usual internet thing of panicking or buying supplements and then arguing with some strangers online, I just want to slow down and look at what Lp little a actually is and what the evidence says and why this so-called Lp little a defray might actually be just a little flickering torch. So one of the big studies worth mentioning is a Japanese cohort study from 2012 called the JMS cohort, which linked low Lp little a with higher cancer rates and higher all-cause mortality, meaning death from basically anything, I guess even things like spontaneous combustion. Now, you heard that right, by the way, lower Lp little a was linked to higher cancer rates and higher all-cause mortality. Now, here's what the study did. And I'll do it in plain English for you. They measured Lp little a at baseline, then followed people over time and tracked the outcomes, especially cancer and deaths from any cause. And what they reported was the The LPA group, or LPLP groups, and I quote, were over-represented among those who later developed cancer or died during follow-up. In other words, the people with the very lowest LPLP didn't necessarily go on to win the Longevity Olympics. Now the phrase over-represented is very telling. The authors did not expect the result, but I doff my cap to them for still publishing it. Now, before anyone sprints off to the pharmacy shouting, quick, raise my P little a immediately, we need to put the brakes on because this is where the fine print does matter. This study was observational, meaning it shows an association, not cause and effect. Nobody was randomized to have low LP little a or told to lower with a drug or surgery. So we can't claim that low LP little a caused cancer or death, but it is a signal, but it's not a verdict. And with population studies, there are always confounders floating around in that metabolic soup, know, genetics, diet, lifestyle, underlying illnesses, you know, the whole lot. Still, it does. raise an important point. The biology of LpA is more nuanced than the headlines make it. Because here's an extra bit that rarely gets airtime. LpA may have some benefits. For example, it seems to show up in the context of wound healing, acting a bit like an acute phase reactant after injury. It can accumulate at sites of vascular damage and may support repair. It may also play a role in the immune defense of our body because it appears able to bind and neutralize certain bacterial toxins, which suggests it's not just hanging around for a laugh. And then there's the whole oxidized lipid angle where LP little a may actually help mop up oxidized phospholipids, potentially protective in some contexts. So depends depending on where those oxidized particles end up, of course. So there's also a hypothesis now emphasis on hypothesis that LP little a could have anti-cancer effects through interactions with growth growth factors or tumor angiogenesis, meaning the process of forming new blood vessels that tumors like to hijack. Now, that part isn't proven in robust human trials, but it's part of the bigger picture. This particle likely has roles that aren't purely as a villain. And that brings us to the awkward truth. Now, despite the tsunami of messaging telling you to lower Lp little a or else, we still don't have the kind of long, term large placebo controlled human trials that definitively prove that deliberately lowering LP-LitLA reduces heart outcomes like heart attacks and strokes, or for that matter, that lowering it increases cancer risk. We have associations and we have genetic approaches. We have indirect effects in the broader lipid lowering trials, but that's not the same as a clean change your LP-LitLA and you change outcomes. We don't have that experiment in humans. So if someone speaks with absolute certainty as if it's ⁓ settled science, it's worth asking, are they talking about direct LP little a targeted outcome trials in humans? or are they leaning on association data and extrapolations because those are not the same thing and treating them as the same thing is how people end up terrified of their own blood work. Now, you'll also occasionally hear the evolutionary mismatch story, which goes something like LPA, or LPLittl-A was useful when our ancestors were getting stabbed and now it's betraying us in the modern world of Netflix and takeaways. ⁓ tidy narrative and biology does love a tidy narrative up until the reality turns up and ruins it. So the mismatch idea assumes LP little a is clearly harmful today. But as I've already covered, you've got this data like the JMS cohort suggesting low levels may associate with higher cancer and higher or cause mortality. If LP little a were purely a relic, you'd expect consistent. consistent evidence that lower is better across the board. And that's not what we see. Plus, we need to remember the proposed protective functions to remember immune defense, wound response, handling oxidized lipids. Well, all of those things are not outdated. Your body still needs to heal. It still needs to fight infection and manage oxidative stress. That's whether you're dodging arrows or you're sitting in traffic. And it's also worth remembering that modern cardiometabolic illness didn't arrive because human biology suddenly changed. Our environment changed, the diet changed, the ultra-processed food arrived, and activity patterns changed, our sleep and stress and toxins, the whole metabolic context that blood markers sit within all changed. Which is exactly why when you're interpreting blood results, you always want to do it in context. And yes, that includes the context of ketogenic or carnivore eating, because physiology does not read mainstream guidelines before it decides what it's going to do. I've done all my things now. Let's make sense of what LP little a actually is because the structure explains a lot of the debate. Now there should be a graphic to help explain this. know, LP little a is basically an LDL like particle, but with a key upgrade or curse, depending on your perspective, it has an LDL style lipid core, but it's attached via a covalent disulf, disulfide bond to apolipoprotein A also called APOA. has three repeating loop structures called Kringle domains named because they look like a Scandinavian pastry yes we're discussing cardiovascular risk using the language of baked goods and that's when science can be quite entertaining anyway ApoA is structurally homogulous to plasminogen, the protein involved in breaking down clots. In simple terms, ApoA is similar in structure and looks a lot like plasminogen, which means it can compete for similar binding sites. And that's where the clot angle comes in, because if you interfere with normal clot breakdown, fibrinolysis, you can theoretically influence thrombotic risk or the risk of clots anyway. So ApoA also contains multiple copies of Kringle 4 domains, one Kringle 5 domain and then a protease like domain that looks as if it should be able to cut proteins but doesn't actually have enzymatic activity. That's like owning a very convincing pair of scissors that are permanently blunt and can't do any cutting. Now, one reason Lp little a varies so wildly between people is genetic. There are different subtypes of these Kringle 4 loops and one particular type KIV2 can appear anywhere from 1 to more than 40 times. So some people inherit a short beads on a string version, others inherit a very long one and that strongly influences LpA little a concentration. This is why LpA is often described as a genetic lottery. Lifestyle can affect many blood markers but with LpA genetics usually has the loudest voice in the room has the biggest influence. So then you've got lysine binding sites, especially in certain cringles, which act like molecular Velcro. These sticky spots help LP little a interact with cell surfaces, the extracellular matrix, basically the scaffolding of tissues and oxidized phospholipids. That stickiness is why LP little a can be argued to contribute to plaque processes known in physiology as atherogenesis. But it's also why it may show up in repair and immune related roles. Same feature, different context, different outcome. So where does that leave you practically when you see your LP little a result? Well it leaves you with nuance which is annoyingly less marketable than fear. The JMS study suggested an association between low LP little a and higher cancer and higher all-course mortality but it doesn't prove causation of course. LP little a appears to have plausible biological roles in wound healing, immunity and handling oxidized lipids. And there are hypotheses about anti-cancer effects, but none of that means high is always good either. And crucially, we still lack definitive human outcome trials showing that deliberately changing LP-LLA changes outcomes in a straightforward way. There are many other studies in this, by the way, you can get them all in the description. So next time someone gasps at their LP-LLA like they're holding a live grenade, remember Remember, it's not just a comic book villain. It's more like a complicated character with questionable PR and a few unexpected redeeming qualities. And if anyone tries to recruit you into fear based supplement funnels, just ask them whether they're working from human interventional trials or whether they're remixing observational data into a horror story for clicks. Anyway, as always, keep your head, keep your humor and keep your interpretation grounded in context, especially if you're in carnivore or keto because context changes what many markers mean and one size fits all medicine rarely fits anyone particularly well and if you'd like to go deeper into this kind of joined up common sense discussion and chat with other like-minded people who aren't allergic to nuance come and join my online community the link is in the description and if today's video helped please consider sharing it with someone who's currently staring at their LP little a result like it's a cursed object from an ancient tomb. Right, I'm off to check whether my LP is lower than my tolerance for internet comments. So I'll see you in the next video. 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