New Data Suggests This Oil Could Help Prevent Alzheimer’s Disease

There's a strong link between the gut and the brain, and what you're seeing here are markers from activated mature microglia. A bacteria, B. ovatus, makes lysophosphatidylcholine , which passes into the brain. MSFD2A transporter that transports it across the blood-brain barrier. A new paper just published in Cell Metabolism has me giddy with excitement. So in my opinion, the best thing you can do to reduce your risk of dementia is to— I have a personal reason to want to know a thing or two about Alzheimer's disease on account of the fact that I carry not one, but two copies of the major risk gene variant for Alzheimer's disease, APOE4. It's actually something that me and Thor, Chris Hemsworth, have in common. But Marvel references aside, and I am a big MCU fan, when I found out that I'm one of these unlucky ones who is vulnerable to Alzheimer's disease, I decided, you know what? These genes won't be my fate. And instead, I'm gonna use this information about myself as motivation early on in my life to pull all the levers at my disposal to prevent Alzheimer's disease and keep my brain healthy well into my 100s. Or in Thor's case, about 1,500 years old. Anyway, I went on to do a PhD in neurometabolism at Oxford. I've written papers on Alzheimer's disease, Alzheimer's prevention, and aim to stay up to date on the literature. And a new paper just published in Cell Metabolism has me giddy with excitement since it provides a potentially accessible and actionable added tool in my Alzheimer's prevention arsenal. One that I want to share with you. So first, for some very high-level background, it's well established there's a strong link between the gut and the brain. Specifically, microbes in your gut, bacteria in your gut, make specific mysterious— I'll elaborate on that in a little bit— metabolites. And these metabolites influence brain health, including cognitive longevity and different forms of neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. Now, what they did in this research study is first look at microbiome patterns that differentiate Alzheimer's mice from control mice, and also confirmed that these same patterns held true in human patients with Alzheimer's disease versus healthy control patients. Indeed, they found patterns, including one I'll highlight: diminished levels of a bacteria called Bacteroides ovatus. Or B. ovatus for short. Here you can see the human data where B. ovatus are diminished in Alzheimer's patients, and the same is true in mice. And impressively, in the mouse model, in the animal model which you can use to show causality and dissect mechanism, treatment of the Alzheimer's mice with this B. ovatus bacteria rescues those mice from the signs and symptoms of Alzheimer's disease. This included a tremendous reduction in amyloid beta accumulation. You can see that here in figures 1i through k. Here you're seeing a hallmark of Alzheimer's disease in green, amyloid beta in the brain, and you can see that treatment with the B. ovatus makes it disappear, or almost disappear. It also, B. ovatus, rescued synaptic function. Here you're looking at the excitatory postsynaptic potentials of neurons, basically how they talk in the brain, and you can see B. ovatus treatment restores cognitive function of the Alzheimer's mice to wild-type function. The B. ovatus treatment also protected against neuroinflammation. And what you're seeing here are markers from activated mature microglia, brain immune cells, and astrocytes. This is all a proxy for gliosis or neuroinflammation. Again, the point is not the jargon. The point is that treatment with the bacteria B. ovatus improves this hallmark of Alzheimer's disease, neuroinflammation. And the B. ovatus improved cognition in functional behavioral tests. Here you're seeing the results from what's called a Morris water maze test. And again, you can see B. ovatus treatment restores cognitive function in the Alzheimer's mice to healthy wild-type function. Again, understanding the exact methods isn't super important, and if you want to, you can go to the paper. But it's important that you comprehend that at multiple levels, what we're seeing here is that this bacteria, has serious beneficial effects on many levels of Alzheimer's pathology and ultimately cognitive function. But that is actually not the important part, at least not in my opinion, because what you really want to know is what mysterious metabolite are the bacteria B. ovatus making that is mediating, that is executing the beneficial effect on the brain? You really care about that because if you can identify it, it's the easiest thing to add back into the body for metabolic benefit. Now, to cut to the chase, the metabolite they identify is so-called lysophosphatidylcholine, or LPC for short. B. ovatus makes lysophosphatidylcholine, LPC, and then LPC is what executes all these beneficial effects we just talked about, reducing amyloid beta accumulation, rescuing synaptic function, reducing neuroinflammation, and overall restoring, improving cognitive function and cognitive longevity. It's the lysophosphatidylcholine that does the work. And they also show how LPC works. LPC has a special transporter called the MSFD2A transporter that transports it across the blood-brain barrier where it binds to a receptor on cell surfaces GPR119, leading to activation of a protein, NRF2, which inhibits cellular death processes, specifically ferroptosis, which is driven by iron-dependent damage to lipids and membranes. So in high-level summary of the mechanisms discovered in this paper, a bacteria, B. ovatus, makes lysophosphatidylcholine, LPC, which passes into the brain via the MSFD2A transporter, binds to receptors GPR119 to ultimately inhibit ferroptosis and cell death, reduce amyloid accumulation, protect against neuroinflammation, and restore cognition, or protect cognitive longevity. Now the kicker is you can actually access lysophosphatidylcholine in food, in particular krill oil, which has a particularly high level of omega-3 lysophosphatidylcholine. To a lesser extent, fish roe and fatty fish also have lysophosphatidylcholine, but krill oil really stands out as the high LPC supplement. Now, given these preclinical data, these mechanistic data, I can't, of course, claim that this will prevent Alzheimer's. But the thing about studying Alzheimer's prevention in humans is it's super, super hard to do rigorously and in a controlled manner because of the nature of the disease, how it takes decades to manifest. You can't really do an easy RCT. So, in my opinion, the best thing you can do to reduce your risk of dementia is to gain an understanding of the metabolism and physiology and neurometabolism, and then use the levers available to you, and of course, common sense. In truth, nothing beats the fundamentals: exercise, including resistance training and cardiovascular, sleep, a good overall diet that maintains metabolic health, with emphasis on omega-3s from fatty fish and possibly krill oil, stress reduction and social connection. But if you're like me and particularly concerned about your cognitive longevity for whatever reason, Well, I find it really reassuring that we are learning more and more about Alzheimer's neurometabolism, and through this knowledge, acquiring means by which we can develop protocols to potentially reduce our risk. And these new data, in my opinion, are one major point in favor of upping lysophosphatidylcholine intake, possibly through krill oil or other supplements to be developed now and in future. So anyway, all this is to say, I'm really excited about what we're learning about the brain. We're starting to unpack what appears to many to be a black box, and through that, gaining knowledge that can be really practical and useful. And to me, it brings a lot of hope. Actually, to get a little sentimental for a moment, one of the things I think about curiosity about metabolism is it does bring forth hope. It brings forth hope that you can always improve, that your genes are not your fate, And also it can be kind of fun if you find people with the right energy to engage with you and be like, guess what? Your metabolic health journey, it's not a chore, it's a privilege, which is why I love doing these papers, bringing them to you. I hope that enthusiasm passes forward and I always appreciate feedback, questions. I hope you found this paper interesting and all the ones that I cover on my channel. So anyway, I'm gonna wrap it up with that. Stay curious and I'll see you in the next one.