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Caffeine is a Potent Anti-inflammatory, Anti-oxidant and Diuretic Agent That Can Also Cause Anxiety and Hypertension Based on CytoSolve Analysis of 36,275 Research Articles, Spanning 132 Years that Include 410 Clinical Trials.

  • Dr.SHIVA Ayyadurai, MIT PhD – Inventor of Email, scientist, engineer, educator – gives an overview on a CytoSolve® computational systems analysis on how Caffeine affects Cardiovascular Health.
  • CytoSolve technology is designed to take a Systems Approach and distilled nearly 35,519 research articles, 1,688 clinical trials, and has been studied for over 55 years.
  • Caffeine is stimulant, anti-inflammatory, anti-oxidant, and a diuretic.
  • Caffeine helps with alertness, increasing energy, lowering fatigue but also can increase restlessness, anxiety, insomnia, and elevate blood pressure.
  • Caffeine reduces nitric oxide production in the blood vessels by inhibiting adenosine receptor, thereby causing hypertension.

The original research in this video is made possible by generous contributions from supporters of the Dr.SHIVA Truth Freedom Health® movement. Please contribute so we may continue to bring you such original research, valuable education, and innovative solutions.


Today we’re going to be talking about the effect of what happens when you drink lots of caffeine in the research. What is the effect of high doses of caffeine on nitric oxide, and particularly cardiovascular health. I think you’re gonna enjoy this because of caffeine, there’s a lot of controversy around coffee and caffeine. Many topics, when you really take a scientific approach of multifaceted, they’re not just left or right. And caffeine is one of those. And that’s one of the things that’s why it’s important to take a systems approach. So before I go into that, I want to, to play a little video for you to all those of you who are new, to really share with you the approach that I take in my journey to actually a systems approach and I hope it inspires you to understand sort of the background of where all of this comes from.

What You Will Learn

We’re going to talk today about the system’s approach to looking at caffeine, coffee. Caffeine is not only in coffee, it’s in tea, it’s in a bunch of substances. And its effect on the cardiovascular system, particularly nitric oxide. Now, one of the things that I think everyone needs to understand is, you know, the research on coffee, or caffeine, frankly, suggests this is there’s a lot of controversy because the conditions in which they’ve done as we started to look at the literature, coffee is frankly, nothing not was done in any consistency. So what we’re doing with our work in CytoSolve, is to really hone in on different aspects. And we may actually have to do many a number of videos on coffee or caffeine in particular. 

Today we will talk about what happens when you consume a different dosages of caffeine, such as one cup of coffee over a 24 hour period, or four cups of coffee over a 24 hour period, or 40 cups over a 24 hour period. And what you find is dosage matters. It’s how much is consumed. And this is something extremely important that we need to understand dosage matters, the amount that matters, because fundamentally everyone’s a unique human being. It is a function of genetics, it’s a function of your epigenetics. It’s a function of the stressors and the conditions you live under. And those three things make you. 

So it’s from a systems approach to recognize it is not just, if this is good or bad, is this pro or anti. And that’s one of the things that I want all of you to get away from. And part of that elevation of consciousness is to take a systems approach. And I think coffee is a good example of that, because it’s actually a lot more complex. So initially, I was only going to do one video, and I realized that when you really start looking at caffeine, that it’s, there’s many, many factors here. So today, we’re going to look at what happens when you give lots or when you look at the dosage of caffeine over periods of time, okay. And as a part of doing this, we’re going to go back and review the cardiovascular system, we’re going to go and look at the nitric oxide system. 

So let’s begin by first of all, we want to look at what caffeine is. So I’m talking about coffee and caffeine, we’re actually looking at caffeine to be specific. And then we’re to look at the biological effect functions of caffeine affects the health benefits and the effects on the cardiovascular system. And then what the clinical evidence says on dosage and so on. Here you see the molecule of caffeine, you notice it has a lot of nitrogens in it and one double bonded oxygen here. It’s got a pentagonal ring structure, and a hexagonal ring structure here. It’s an interesting molecule. You can’t ignore a lot of these nitrogens here, and it’s the most widely taken psychoactive stimulant globally. It is also a natural pesticide, which is interesting. And it’s naturally found in more than 60 plants. So caffeine doesn’t only occur in coffee, but occurs in chocolate, kola nuts, guarana berries, tea leaves, yerba mate, etc. So you can see there’s more than 60 plants. So just think a little more broadly, when you think about caffeine is not just coffee, it occurs in many, many different plants

Over 35,000 research articles have been done on caffeine, nearly as you can see, over 1600 clinical trials over a period of 55 years. So a lot of research has really kicked in on coffee over the last 50 years or so you can see this graph here on the bottom, how much of that research has been happening, but a lot of articles we did when we looked at arguing and cardiovascular health data close to 130,000. Tremendous amount of work, but caffeine is up there about 35,000 articles. So how do you go about finding what’s really going on? So as many of you know, I like to take a systems approach. So how do you take all of these articles and figure out what’s going on? 


So from my PhD work, as many of you know, many years ago at MIT, I created a technology platform called CytoSolve. Where we can really look at instead of cherry picking which is a non systems approach. We can look at it systematically and look at what the known researchers organize that literature, as I’ll share with you here using the CytoSolve methodology. And we can sustain ourselves on our platform. It’s really a platform for doing discovery faster, cheaper and safer. We can look at a particular molecular area. So what we’re doing with CytoSolve was we’re literally looking at the particulars of an ingredient, in this case, caffeine and how it affects the complexity of a molecular system. And the molecular system we’re gonna look at is nitric oxide, as we’ve talked about the release of nitric oxide, because nitric oxide is an important biomarker, which means an indicator of cardiovascular health. It supports vasodilation, lowers blood pressure, it was the core of the discovery of viagra, for example. So that’s why we’re going to look at the effects of nitric oxide on that. 

So CytoSolve really helps us do this. It is organized and inside itself comes from recognizing the entire pharmaceutical model of developing a drug, which is a single molecule drug. Typically, they tested in a test tube, and then they tested on animals. This is a research process, finding out if something works or not. And then you go to human trials, this can take up to 13 years by billion dollars. And what’s happening is, as drug companies spend more and more money on this antiquated process, they’re in fact discovering less and less new drugs, which are in fact being allowed by the FDA. So this process is broken. And that really led me to develop cytosol. 

We’ve applied that systems approach here to understand how caffeine in particular works. For many years, we’ve helped some of the largest nutritional companies and even small companies who are putting together products, figure out if their formulations actually work, right now, if you go to Whole Foods or you go on supplements, there’s a lot of snake oil out there, it’s hard to know what actually works with cytosol. But we’re able to take the known science, which is varying at any point in time. We organize the science where we extract the molecular pathways and molecular reactions. Let’s say you want to look at brain health or cardiovascular health, and use a computer to organize that. And then using that we can look at how different ingredients work on the computer long before we go hurt people.

 So about several years ago, we said hey, why don’t you sign us up to actually help, you know, people that we know, directly. So what we did was we looked at all the molecular pathways of pain and inflammation. And we organize all of that. And then we looked at all different kinds of natural ingredients. And we found a combination of ingredients that appear to have some very powerful effect for, you know, reducing pain and discomfort, you know, and swelling and discomfort. And this is exciting because the first time we’ve ever gone, and by doing the research, doing the analysis, doing the computation, and then actually creating a product, it’s called mV25. It’s out there.  So we have more supply now coming. I know some of you are pre ordering. 

So just briefly, what is mV25. It’s a very interesting product where you can notice that the branding is of a scientist myself from a system standpoint. And we’ve used the equation in math and physics called momentum, mass times velocity, its momentum to move. And you can see it’s a blend that’s been CytoSolve optimized. And if you go to the back of the label, it explains that what CytoSolve optimized means that this was formulated using the computational engine, the technology for precision and personalized medicine that came out of my doctoral research at MIT. And this formulation results from integrating 1000s of those peer reviewed journal articles over four decades in 68 research institutions, and we’ve computed trillions of potential combinations of biomolecular interactions, to discover an optimal synergy of competence. 

This formula has been optimized to maximize benefits and the other pieces as Science advances, so we will. So that’s the promise that we’re making in this very revolutionary approach. So and by the way, it’s certified clean, it’s GMP and it’s made in the US. So if you want to go find it, you can go right up on the website and find it right up there. 


So when we look at caffeine now, from a systems approach, what do we find? We find that it’s in many ways, a drug, a medicine. It’s a plant-derived tri-methyl xanthine alkaloid. These are plant alkaloids that can have psychoactive effects. So caffeine is psychoactive. And as you can see here, it’s a tri-methyl xanthine alkaloid. The average dietary caffeine consumption in the US adults is around 200 milligrams per day. And the half life of adults is three to seven hours. What does Half Life mean? Half Life means how long it stays in your house, basically means within, let’s say, three hours is a half life. That means if you consume 200 milligrams of caffeine, the amount that’s in your blood when you first consume it, three hours later, you have that 100 milligrams, or what, three hours later, it will go down and 50 milligrams and so on. 

The half life is important because it shows how much your liver can clearly. So you have a cup of coffee and it depends on the individual. I mean, if I have one cup of coffee, in the middle of the day, it’s hard for me to go to sleep at night. So it dissipates very slowly for me, other people, they clear it quickly. It depends on your appetite for it. 

Now let’s look at the biological effects. Well, first of all, coffee, as most people know, is a stimulant for the nervous system. It is anti-inflammatory. It’s an antioxidant. And it is a diuretic, which means you drink it, you’re going to remove water out of your system, but it’s a stimulant for the central nervous system, but it also has these other properties. Again, this is what we know, based on the known research today, it could have other things again, this is based on the known science across those 35,000 papers. 

What are the health benefits, it’s got a number of health benefits. I’m sure most people know it makes you more alert. It increases your energy. It has anti carcinogenic effects, anti cancer, anti neurodegenerative disease, Alzheimer’s disease and Parkinson’s. It also improves your physical endurance and recovery. It reduces fatigue, improves, improves focus and does support weight loss. 

The adverse effects are also documented in the literature, and the scientists can get you very anxious, it can get you restless, it can cause blurred vision, insomnia, muscle twitches, or tremors, elevated or irregular heart rate and elevated blood pressure. I just want to emphasize that everyone’s a unique person. There are some people who drink a lot of coffee, and they seem absolutely fine, their systems may be different. This research is based on sort of the norm that’s coming out from those papers. By the way, the body from a systems Eastern approach, the anxiety and restlessness is called a Vata aspect. And I teach this in our course, those of you look at Ayurveda and other Eastern systems of medicine. For some people, if they drink lots of coffee, it is going to wire them even more.  So it depends on your body type. So that’s important to remember, not one size does not fit all. Again, that’s what a systems approach teaches us. 

Cardiovascular System

When we look at the cardiovascular system, you have two sides of your heart. And you have the bottom top and bottom, the top of the heart is called the atrium, the left and right atrium, and the bottom of the heart is called the ventricles. Now, on your, on your left atrium is where you know, blood is coming in, which is the top left side of the heart, fresh blood comes in, fresh blood comes in. And then it’s pumped down to the left ventricle, which then pumps out through the aorta, which is the main artery, as you see over here, through all the different parts of your body. So all this oxygenated blood goes. And then what happens is, as your blood uses of that oxygen, the vena cava, brings back the deoxygenated blood to the right atrium, which then sends it down to the right ventricle, which then pumps all that deoxygenated blood to the lungs, and they get re perfused with oxygen. And that’s how the pump works. 

So the cardiovascular system has three subsystems: a heart, which is a pump, as you can see, it’s a powerful pump, which pumps the blood; the blood vessels, and we’re going to look at that which carry the blood and nutrients, all sorts of the body; and, then you have the actual blood, which is the transport oxygen, and supports your immune system. 

The cardiovascular system really has three parts of the vascular system: you have the aorta, or the arteries, which are in the red color, you have the veins, the arteries are the ones that carry oxygen and blood. The veins are the things that carry deoxygenated blood, but they’re interconnected by the capillaries, the capillaries are taking the oxygenated blood through to your tissues and your cells. And then they’re also helping remove the waste of the carbon dioxide, which then flows into your veins and out. The arteries and veins have three layers: the outer structure is known as the tunica adventitia that’s really the structural support. It’s like the bark of a tree. The middle of it is a tunic media, which is a middle layer, which is more of the musculature of the arteries here, the middle here are the veins, and then the inner part of the arteries and the vein is composed of what’s called the tunica intima, which is the endothelial cells. Capillaries, which are the fine blood vessels, are composed of endothelial cells.

Nitric oxide is extremely important to understand. Many years ago, Time magazine had an article saying how nitric oxide is a molecule of the century, because nitric oxide is important for the dilation of vessels, which affects blood pressure, hypertension, etc. So when you exercise for example, blood starts flowing through your arteries and your veins and, and your capillaries. Remember, the capillaries are composed of these things called endothelial cells. So when the blood flows over the endothelium, our research with MIT and a bunch of other institutions showed that your body will release nitric oxide. Okay, so exercise is very valuable. In the presence of arginine the body will release nitric oxide. 

So when you look at the nitric oxide here, what you’ll notice here is that nitric oxide is a molecule with nitrogen double bond to the oxygen. Its key role is maintaining blood pressure. It’s anti-atherogenic. And it’s generated when endothelial nitric oxide synthase (eNOS), which is an enzyme catalyzes arginine. When you exercise, it triggers nitric oxide production. On the inner surface of those capillaries are endothelial cells. When you exercise, in the presence of arginine, eNOS will create nitric oxide as well as l citrulline. And this causes vasodilation. 

CytoSolve collaborated with MIT, Brigham and Women’s Hospital, Harvard and King’s College. And we did some very interesting work, looking at what happens when you move blood through your arteries. So here’s arterial flow. And we’re gonna it’s almost like we’re gonna take a microscope, and we’re going to look deep into the surface of the capillary, you have these little endothelial cells, this is one cell. And on the cell surface right over here, if you can see is a very interesting structure that looks like a Christmas tree. So when blood flows over these endothelial cells, the Christmas tree structure starts shaking. And when this shakes, through a series of chemical reactions, nitric oxide is released. The mechanical force of the structure called the glycocalyx, in the presence of arginine releases nitric oxide. 

When we use CytoSolve, and look at the research, we find every research that has chemical reactions, put all of those reactions together versus cherry picking the data. We’re able to interconnect them on the computer, not by killing animals, but on the computer, we interconnected them. And we can find out how much nitric oxide gets released. And this is CytoSolve’s simulated prediction on this slide. We’ve shown that when we did actual laboratory experiments, CytoSolve matches the lab experiments very closely. The black line represents our predictions and the dots here represent Andrew, who’s work at Harvard and MIT showing how much is actually released, measured. So this was published in one of the leading journals in the world – CELL’s Biophysical Journal, and I was one of the key authors with two other senior authors.

Effect of Caffeine on Cardiovascular System

What I just shared with you here is that we have a proven mathematical model where we looked at all of these chemical equations of the release of nitric oxide, so we modeled that and we published that so it’s validated. Then we asked, what happens now when you take caffeine, what happens when you take lots of caffeine and different dosages? So let’s look at that. So what happens when you just take one cup of coffee? And let’s assume you’re sipping this over a 24 hour period. So the y axis is nitric oxide, And the x axis is how much of that caffeine ends up in your blood, and it’s micromolar amounts. How much ends up at the cell surface. So we’re looking at about 10 micromolar, is what ends up right, that’s what 10 micromolar. So just to be clear, what we’re simulating here, using this proven CytoSolve model of a cell, how much caffeine actually after you’ve digested it onto your bloodstream ends up at the cell surface over that 24 hour period. T

So you can see your nitric oxide level drops, it was at 100%. So it drops down to around 85 to 80%. So the key takeaway is, if you drink one cup of coffee, it will lower your nitric oxide levels. Okay, nitric oxide is important for vasodilation. So that’s what this result shows. Now, let’s look at what happens if you drink four cups of coffee. When you drink four cups of coffee, you increase the level of caffeine in your blood plasma to 48 micromolar. You’ve reduced your nitric oxide production rate down from 100% to 70%. It’s not that bad, but your energy levels are low. So the takeaway there is, you now assume you’re drinking four cups of coffee over a 24 hour period, your nitric oxide level will go down. Remember, nitric oxide is important, again, for cardiovascular health. 

Next, what we did was, there are supplements that bodybuilders take or people want to stay awake take that are the equivalent of 40 cups of coffee, or some people take a shot of this. All right. And so what happens when you take something like that, and what you see here

is that when you take these caffeine supplements, which are the equivalent of 40 cups of coffee, over 24 hours, you can see that your annual level drops down to 60%. Okay, from 100 to 60%. Now, this is for a normal individual, okay, there are people who have cardiovascular issues, hypertension. Tomorrow, I will do a video where we look at what happens when you take arginine and caffeine together. That’s the side of analysis at different levels of hypertension and you can see some people’s and all levels will go down even to 40%. What we’re looking at here is a normal individual. This research is documented, and we published this in the Journal of Dietary Supplementation on caffeine. It was a research done with the US pharmacopoeia and I was one of the senior authors on it. 

Synergy – A Systems Principle

So nature one of the things that I teach, you know, every Monday evenings as a part of our movement, to educate people, activate people give people social media tools, the Truth Freedom Health, an education program every Monday evenings, I teach people in about three hours Systems Thinking, because it is what systems thinking is how we can see the interconnection between the universe, your own body and things at the microscopic level, you can understand political systems. So I want to encourage all of you. When I’m talking about Bitter Gourd, I’m talking about these foods, foods are not like a drug where it just affects one thing. They have a synergistic reaction, they affect multiple pieces. And so you can apply the same principle, getting back to the political aspects to Truth Freedom Health.

Truth Freedom Health®

So the movement for truth typically is with scientists and nerds, quote, unquote, nerds, people want science and truth. So that’s in one little world. And then typically, the movement for you know, freedom is done by people who support the First Amendment, the Second amendment and they’re in their own little cubby holes. And then people aren’t eating well and organic food is earthy, crunchy granola types. But the problem is that we can’t win if all these movements are independent, we need to bring them together. So which is how we go beyond Left and Right, right. Freedom is essential for us to practice science to get to truth. And truth is how we find out what’s right for our bodies or for our environment. And without health is really the infrastructure to support Truth Freedom Health. So I want to encourage all of you to recognize that food is a system your body is a system systems interact. It’s not any one thing. We can’t just have the science guys over here. Doing their science searching for truth. We can just have the 1A and the 2A people for the First and the Second Amendment people, we can just have people doing yoga and thinking they’re great. All of these movements need to come together from a Systems Approach. Because without freedom, we can’t really get to health and without health, we won’t have the strength to fight for truth, or, freedom. So I’m going to play a little video now. And then we’ll come back and finish a Bitter Gourd. So all of you understand that we need to build a movement for Truth Freedom Health. And such a movement is a Systems Approach to winning.

Caffeine – Eastern & Engineering Systems Approach

So when we look at caffeine, we take that systems approach. So when we look at caffeine, you can look at it from a system standpoint. So for example, one of the tools that you get when you become a truth freedom, warrior or supporter, you get this very powerful tool called Your Body, Your System, which helps you look at the body from the from an energetic standpoint, the movement of energy, which is transport, the “T”, the conversion of energy, “C”, and the storage of energy, “S”. And then you can answer a set of questions, self analysis, and you can figure out what kind of system you are, which is that, this triangular space, then you can figure out through another set of questions where your body is today, which is that black dot, and then you can figure out how supplements and foods affect your body as a system to bring you back into where you should be. 

Now, what does coffee do? Well, coffee increases transport motion in your body. In the eastern System Science, they call it increasing Vata – transport. Coffee also increases conversion, right, you move faster. You start motion. It’s a diuretic, which means it increases the movement, the flow of water. You drink a lot of coffee, go to the bathroom a lot. And it also stabilizes kapha, which means storage. So that’s what coffee does. 


Now, how much should you take? Well, the daily consumption, according to Nawrot et al., is no more than 400 milligrams of coffee. Again, this is for the average individual. We know about one cup of coffee with around 200 milligrams of caffeine. That’s sort of seen as a consumption limit for cognition improvement, but 150 milligrams per day. 150 milligrams, for headache. Okay, so 300 to 500 milligrams per day. So that’s what’s known again, you should consult your doctor, this is not a medical show. This is essentially a distillation of what’s out in the literature. So in closing, caffeine is really a double edged sword and I want people to really remember this. 

Thank you, everyone. Be well.

It’s time we move beyond the Left vs. Right, Republican vs. Democrat. It’s time YOU learn how to apply a systems approach to get the Truth Freedom Health you need and deserve. Become a Truth Freedom Health® Warrior.

Join the VASHIVA community – an integrated EDUCATIONAL, COMMUNICATIONS – independent of Big Tech -, and LOCAL ACTIVISM platform to empower YOU to actualize Truth Freedom Health in your local communities by employing a SYSTEMS APPROACH.

The platform we are building for Truth Freedom Health® provides the infrastructure to take on Big Tech, Big Pharma, and Big Academia. Many of you have asked how you can help. You can contribute whatever you can. Based on your level of commitment to get educated, I have also created some wonderful educational gifts to thank you for your contribution.

To get the education you need and deserve, join Dr.SHIVA on his Foundations of Systems course. This course will provide you three pillars of knowledge with the Foundation of Systems Thinking. The three pillars include: 1) The System Dynamics of Truth Freedom Health, 2) The Power of a Bottom’s Up Movement, and 3) The Not So Obvious Establishment. In this course, you will also learn fundamental principles of all systems including your body.

Course registration includes access to his LIVE Monday training, access to the Your Body, Your System tool, four (4) eBooks including the bestselling System and Revolution, access to the Systems Health portal and communications tools – independent of Big Tech – including a forum and social media for you to build community with other Truth Freedom Health Warriors.

This course is available online for you to study at your own pace.

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