Transcription
Vitamin C is everywhere in your fruits and your vegetables and your multivitamin, if you take one. But when it comes to heart health, vitamin C is wildly underrated. We think we understand it, but we don't. And what I found when I dove into the science shocked me. But we're going to unravel that mystery of vitamin C here together today. And I'm going to arm you with practical insights that will help your heart. And if, if you can make it through to the end, I have a reward for you. But you do need to watch the full video to fully appreciate and understand the reward, which comes in the form of a protocol.
But first, a quick hat tip to what had me running down this vitamin C rabbit hole. I recently did some research and did a video and wrote a newsletter on Lp(a). Ended up being quite popular, and I encourage you to check that out if you're interested in heart health. But this video will be self-contained. So here's what you need to know. Lp(a) is a life-approaching particle. It's kind of like LDL's evil twin. The one that went to villain school and graduated the top of its class in blood clotting. Hey everybody, I'm number one. And Lp(a) is thought to be genetically cemented, genetically determined. And it's become the new hotness in the cardiology world. Perhaps because there are five new drugs in development to radically lower this Lp(a). However, even beyond these medications, some people anecdotally report success lowering their genetically determined Lp(a) with high-dose vitamin C supplementation. That's weird, right? Well, it makes some sense, and that is where we are going to start our journey into nutrition and biology today after I give you a road map of all we're going to cover in this video, which are broken into eight chapters. That's eight.
First, we're going to talk about vitamin C and Lp(a): nature's interesting substitution. Then, we're going to talk about vitamin C in heart disease, going over the human data, the epidemiology, and the control trials. Then we're going to talk more about mechanism: vitamin C in oxidized LDL. Can vitamin C stop cholesterol from turning toxic? Then we're going to talk about vitamin C and nitric oxide and blood vessel health. Why your blood vessels care. Before kind of stepping back and providing a mechanistic summary so you can get a big picture overview about the three prongs by which vitamin C can help your heart. Then we're going to talk about vitamin C dosing. How much do you really need? What's optimal? Are the RDAs correct? And what are the best whole food sources? And then we're really going to get into the nitty-gritty and talk about vitamin C and lysine, the amino acid lysine. And I call this the Batman and Robin pair of nutrients for heart health. Finally, we're going to take a step back and puzzle together the protocol, which you will understand by the end. And lastly, this time for real, before we dig into this topic, I want to warn you. The deeper you go in this video, the more complex the topics become. And if you can get through chapter 7, the vitamin C and lysine one, you've earned my intellectual respect. But with that, let's really begin.
Chapter one, vitamin C and Lp(a). Lp(a) is a spherical particle that floats around in the blood. It looks like an LDL particle, except Lp(a) also has a protein tail called apolipoprotein(a). And this tail endows Lp(a) with the ability to promote blood clots. And this is one way in which Lp(a) is thought to promote cardiovascular disease and atherosclerosis. But in 1990, the double Nobel laureate Linus Pauling and his colleague Dr. Rath came up with a very interesting idea about Lp(a). They hypothesized that Lp(a) was a surrogate for vitamin C. Now, as a quick terminology lesson and kind of a fun fact, vitamin C is also known as ascorbate or ascorbic acid, and it got this name given its antiscorbutic properties, which means the effect of curing scurvy. Kind of makes sense, right? And I only mention this so that if you look at the papers I referenced, you know that ascorbate just means vitamin C. Anyway, most mammals can synthesize their own vitamin C. But about 40 to 60 million years ago, our primate lineage developed a mutation in the GLO gene that prevents us from synthesizing vitamin C. We can't make our own vitamin C. And since vitamin C helps promote wound healing, this placed an environmental pressure to develop alternative means to promote wound healing and halt bleeding. In effect, evolution called for a substitute, which it found in Lp(a), which can likewise bind to clots and promote wound healing.
Now, if it were true that Lp(a) is actually an evolutionary substitute and surrogate for vitamin C, we might expect a pattern whereby animals that synthesize vitamin C lack Lp(a). This is indeed the case. And what's more, species that have lost the ability to synthesize vitamin C, like us, and this includes guinea pigs and the European hedgehog, they also produce Lp(a). So across the animal kingdom, there's this interesting pattern where the ability to synthesize vitamin C remains, Lp(a) is largely missing, and where the ability to synthesize vitamin C is lost, Lp(a) is present. And this provides one comparative evolution argument that Lp(a) might really be a surrogate for vitamin C. But this intrigue doesn't stop there. Chasing on these observations, Pauling and Rath performed various experiments. In one, they deprived guinea pigs of vitamin C, which was sufficient to cause these guinea pigs to develop rapid heart disease, rapid atherosclerosis, characterized by plaques that were filled with Lp(a). Conversely, when the guinea pigs were given vitamin C, negligible amounts of Lp(a) could be found in their arteries. Pretty fascinating.
Now, I want to shift gears and review some of the human data before we get back to mechanisms. So, chapter 2, vitamin C in heart disease in humans. We're going to start with the epidemiology. One possible implication of the Pauling and Rath hypothesis is that higher levels of vitamin C in humans could slow the progression of heart disease, atherosclerosis. Exactly how it does so with respect to Lp(a) modification and other mechanisms deserves more unpacking, and we will get there, I promise. But let's first ask the general question: does vitamin C appear to protect against cardiovascular disease in humans? And in four words, the data are mixed, kind of like feelings about pineapple pizza. However, there are some positive signals. For example, in the Nurses' Health Study, vitamin C intake from supplements was associated with lower risk of coronary heart disease, and in the EPIC study, circulating levels of vitamin C were inversely associated with death from cardiovascular disease and ischemic heart disease.
Now, one obvious and important caveat is one cannot draw cause and effect relationships from these epidemiological studies, and other studies have shown negative results. However, the fact that there is any positive signal, I think, is interesting. And when this is the case and the data seem confused and inconsistent, what I look to do is ask these questions: Could it be that there are responders, those who benefit from vitamin C, and non-responders, those who don't? And if so, what determines who is a responder and who is a non-responder? These are important questions to ask and answer because sometimes in nutrition science, lumping together diverse groups of people can lead us to lose sight of the biological truth through the haze of biological heterogeneity. We are all so different, and lumping us together can confuse topics. We will return to this idea of responder versus non-responder momentarily after we discuss the results of some controlled trials and mechanisms by which vitamin C may be cardioprotective, even beyond Lp(a).
So with respect to the control trials, there have been several successful control trials showing benefits of vitamin C supplementation on heart health. For example, in one double-blinded randomized control trial on 46 patients with coronary artery disease, one group was given a single dose of 2 g of vitamin C and then longer-term treatment with 500 mg of vitamin C, and this was compared to a placebo control. The outcome they were looking at in this study was something called flow-mediated dilation, which just refers to the widening of an artery in response to an increase in blood flow. This flow-mediated dilation test is a non-invasive test to assess the function of the lining of blood vessels and overall blood vessel health. And what they found in this controlled trial is both the single dose and long-term treatment with vitamin C improved blood vessel function. The positive effect was also generalized to both men and women, in those taking cholesterol-lowering medications and not. So it was pretty generalizable.
As another example, in a different randomized trial, in patients undergoing a blood filtering procedure called hemodialysis, the patients were randomized to receive either a placebo or one of two doses of vitamin C, either 300 mg or 600 mg, given intravenously directly into the blood three times per week for 3 months. Now, because of the nature of these patients, they had all undergone a procedure called angioplasty that widens their blood vessels. And a major concern after this procedure is that the blood vessels will clot up again. This is called restenosis. So, simplifying and setting aside the medical jargon, the desired outcome and hypothesis was that vitamin C would slow the rate at which blood vessels narrow and clog up. And indeed, they found that higher dose vitamin C significantly slowed restenosis by half, keeping the blood vessels open wider and for longer. And in yet another 6-year study that measured atherosclerosis progression by carotid intima-media thickness ultrasound of the carotids, supplementation with vitamin C and vitamin E slowed progression of atherosclerosis by 26%. So the big picture point is, in both the epidemiological literature and controlled trial literature, there are signs that vitamin C slows the progression of cardiovascular disease.
Now, let's return to mechanisms in chapter 3. Vitamin C and oxidized LDL. In addition to potentially reducing or diffusing, I'll explain what that means in a minute, Lp(a), vitamin C acts as an antioxidant and can therefore reduce oxidative damage to the blood vessel lining, proteins, and fragile fats. And this includes reducing oxidized LDL levels. In one control trial, supplementation with 500 mg per day of vitamin C lowered oxidized LDL from 87 to 71 units per liter, representing an 18% reduction, which occurred with no significant changes in overall cholesterol levels. It just lowered the oxidized LDL. Additionally, vitamin C can act downstream to protect smooth muscle cells in blood vessels from the harmful effects of oxidized LDL. Now, a key feature of atherosclerotic plaques are dead necrotic cores, including the death of smooth muscle cells in the lining of the blood vessel wall. And one study found that vitamin C defended against the death of these smooth muscle cells when exposed to oxidized LDL. This provides another potential protective benefit of vitamin C against atherosclerosis.
But moving on, chapter 4, vitamin C and nitric oxide. Recall earlier, just a moment ago, we reviewed a trial where vitamin C improved blood vessel function. Now, if you're curious, and I know you are, then perhaps you were scratching your chin and asking yourself, "But how?" Well, a key signaling molecule in blood vessels is called nitric oxide. It's a gaseous hormone that helps blood vessels flex and expand, promoting proper blood flow and nutrient delivery. And nitric oxide is synthesized by nitric oxide synthase enzymes. And these NOS enzymes require co-factors, which are basically molecular assistants. And one key co-factor is called, ready for it? Tetrahydrobiopterin. Try saying that five times fast. Or BH4 for short. Now here's the punch line. Data show that vitamin C can stabilize this BH4 co-factor. This means improving the function of the NOS enzymes and increasing nitric oxide production. This in turn supports proper blood vessel function, as reflected in the human trial data we reviewed earlier. Pretty cool, right?
But now let's do a mechanistic summary. Let's take a step back and piece the puzzle together. Vitamin C can diffuse the Lp(a) bomb. More on that coming up soon. Limit oxidative damage to vessels and lipoproteins, reduce oxidized LDL, and promote better blood flow by enhancing nitric oxide synthesis. And through these three mechanisms and possibly more, vitamin C can help support your heart health. Laying it out this way also helps us understand why the human data might look so mixed and some people might benefit more from vitamin C than others. For example, those with genetically high Lp(a), like me, could potentially benefit a lot more from mechanism 1, diffusing Lp(a). Whereas those with more overall oxidative stress and lower antioxidant capacity might benefit more from mechanism 2. And those with higher blood pressure and worse blood vessel function might benefit more from mechanism 3. So you can see how different people might respond differently based on their predisposing risk factors. Makes sense, right? Okay.
Chapter six, dosing. The recommended daily allowance for vitamin C is 90 mg for men and 75 mg for women. This is not designed to be a target for optimal levels. This is actually often true of recommended daily allowances for nutrient targets. For example, the RDA for protein is 0.36 grams per pound of body weight, which is the equivalent of a single large chicken breast for a fully grown adult male. And the RDA for vitamin D is only 600 international units, which is far lower than recommended by most informed practitioners. So, as a general guideline, the RDA does not equal optimal levels. But that doesn't answer the question of how much vitamin C you should consume. Now, there's no easy answer, but based on available data, balanced with consideration of what I think is tolerable for most people, I would suggest anything between 250 mg and 2,000 mg or 2 g per day. And take that range with a grain of salt. It's not a precise science. But now, I know many of you will want to know about the vitamin C rankings of different fruits and vegetables. So, here's your first gift. It's a table of the 15 common fruits and vegetables ranked by their vitamin C content per 100 grams and also highlighted in terms of their vitamin C to net carbohydrate ratio. Personally, I think the ratio is valuable since it suggests how you can get the most vitamin C bang for your sugar buck. So, you can pause the video here and just screenshot this table. My gift to you. Now, moving on.
Seven. This is where things get, I think, extra fun and dorky. Vitamin C and lysine, the Batman and Robin nutrients for heart health. With all that behind us, I want to bring you to medical school. Now, specifically, I want to talk to you about a clotting process called fibrinolysis, which is one of those pathways every doctor learns about in medical school, but most forget. Fibrinolysis refers to the breaking down of blood clots. Fibrinolysis is a normal body process that prevents blood clots that occur naturally from growing too large and causing problems like clogging up your arteries and causing heart attacks. Now, for fibrinolysis, the breaking down of blood clots to occur, an enzyme called plasminogen needs to be converted into its active form called plasmin. And the plasmin then chops up the fibers, the fibrin that hold the clot together, and this allows the clot to break down. Now, the apolipoprotein(a) tail of Lp(a) is basically a modified copy of plasminogen, but one that is deactivated, for lack of a better term. So Lp(a) competes with plasminogen and in so doing, it effectively boxes out the enzyme that should break down clots, and this is in part how Lp(a) makes the blood more clotty.
Now, here's the interesting thing. How does the Lp(a) tail actually bind to clots? It does so with something called lysine binding sites. Lysine is an amino acid, a building block of proteins, and it's the handhold for Lp(a)'s tail. So to summarize before I give you the punchline as related to vitamin C, Lp(a) binds to clots using lysine binding sites. It thereby competes with the normal clot breakdown machinery, allowing the clot to grow. And as an aside and to reinforce the critical importance of these lysine binding sites, I want to highlight that experiments were conducted where mice were given the gene to produce Lp(a). Remember, mice don't usually produce Lp(a). However, when this was done, mice were given one of two different copies of the gene. One had intact lysine binding sites, and the other one had their lysine binding sites modified to decrease the lysine binding activity by 80%. So those mice that produced Lp(a) with intact lysine binding sites, they showed a fivefold increase in atherosclerosis progression of plaque versus those with the Lp(a) that only had 1/5th the lysine binding activity. Pretty cool, right? Basically, Lp(a) without lysine binding sites is like a rock climber without hands.
Now, I'm going to explain to you how vitamin C is Batman, lysine is Robin, and Lp(a) is the Joker trying to clog Gotham's arteries. First, vitamin C activates an enzyme, lysyl hydroxylase, which converts lysine to hydroxylysine. And this process is essential for the formation of strong, stable collagen fibers that can decrease the molecular handholds for Lp(a). Have the rock climber take away his hands. Basically, vitamin C can help make Lp(a) less sticky, even if it doesn't decrease Lp(a) levels. Additionally, lysine supplementation, which is safe up to 6 g per day, can increase circulating lysine levels that bind to the lysine binding sites on Lp(a), effectively creating molecular decoys that can also help make Lp(a) less sticky. So in this way, we can envision a simple nutritional protocol consisting of routine vitamin C and lysine supplementation that collectively could decrease the harm of Lp(a), either by decreasing its levels or, far more likely, by just making it less sticky and less atherogenic.
And that brings us to chapter 8. I want to reward those of you who stuck with me to this point with a protocol to help combat your Lp(a). It was important to me not to just hand this to you up front, but I really wanted to walk you through the science so you truly understand the why behind this cheap and simple method. I propose quite simply dosing vitamin C, 1,000 mg per day, one gram per day, taken in two separate 500 mg doses. Also, 2 grams of lysine per day. The logic here is that this combination may help diffuse your Lp(a), at least to some degree. As we've reviewed, this protocol should make Lp(a) less sticky while also helping to reduce your oxidized LDL and potentially improve nitric oxide production and blood vessel function.
But now, how do you know I'm not just a clever trickster? How do you know this is actually helping? Well, aside from the fact that I've not yet been bought out by big orange juice and have no motivation to mislead you, you can get tests if you'd like to monitor how this protocol affects you. Here are some tests I suggest that could be the most informative. First, get your Lp(a). You should know your baseline levels. Getting before and after Lp(a) measurements could be interesting. Although, to be perfectly candid, I wouldn't expect to see major changes. While the animal model data suggests vitamin C supplementation can lower Lp(a), and people have reported this anecdotally, so I think there's a possibility, the published human data are less compelling. The presumed benefit is in making Lp(a) less sticky, thereby reducing its accumulation in arteries. But unless you can find a doctor to biopsy your aorta, you can't exactly measure the accumulation of Lp(a) in your arteries while you're alive. Still, I think the before and after test could be interesting. Maybe you will see a reduction. If you do, tell me. If you don't, also tell me.
You also want to get your vitamin C levels. See how supplementation changes your circulating vitamin C levels, maybe after 4 to 8 weeks of supplementation. Also, getting oxidized LDL and oxidized phospholipid measures, their markers of oxidative stress, could be really interesting, and one would hope to see a reduction in these with vitamin C supplementation. Finally, you can get measured an IL-6. IL-6 is an inflammatory molecule that can both signal to the Lp(a) gene to increase Lp(a) production and independently IL-6 promotes atherosclerosis. Interestingly, data suggests that IL-6 and Lp(a) can synergize to accelerate plaque progression, and that inhibiting IL-6 can actually lower Lp(a). So, there's still that possibility there. Additionally, human studies show that vitamin C supplementation can lower IL-6 levels. So, while I'm not sure vitamin C will reduce your measured Lp(a) levels, it might, I do think you'll see a decrease in IL-6 if it's elevated at baseline. So, I think it's worth measuring. Of course, this is not a prescription, just a logical and safe protocol derived from the science we've reviewed together today and transparently shared.
Finally, my only ask to you, if you appreciate the effort that goes into communicating nuanced science here on this channel, and if you found this video interesting and valuable, please do like Lp(a) with intact lysine binding sites and grab on to that subscribe button. I'd really appreciate it. It gives the algorithm a signal that you want more nuanced science so I can keep doing what I do here on this channel and scale it up. Thanks again. Stay curious and go enjoy some strawberries. [Music]