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In this discussion, Dr. Shiva Ayyadurai, MIT PhD, the Inventor of Email, presents a special scientific lecture on a seminal paper that was recently published in a high impact journal sharing a breakthrough methodology for quantifying the synergistic effects of multi-combination nutraceuticals and dietary supplements.

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.


  • Dr. Shiva’s CytoSolve® allows for a breakthrough methodology that is far from how Big Pharma and Big Vitamin currently operate.
  • mV25™ is a product made with CytoSolve®, a revolution of health.  
  • Dr.Shiva shares CytoSolve® and the Open Science Institute. The projects, stages, and out of those efforts how mV25™ emerged from this.
  • The framework of Systems architecture of joint pain and identifying the molecular mechanisms that affect the joints for osteoarthritis. The different biomarkers of chemicals that increase when you have pain and inflammation.
  • Bioflavonoid combinations of mV25™ ingredients, and the alchemy for optimum health from compounds found in foods that affect the pain biomarkers in osteoarthritis.
  • CytoSolve®’s potent combinations and quantification of synergistic effects for mV25™. Examples of antagonistic, additive, and synergistic effects based on dosage

Dr. Shiva’s CytoSolve® allows for a breakthrough methodology that is far from how Big Pharma and Big Vitamin currently operate.

There Is a breakthrough methodology to figure out which supplements work and which don’t. This concept of Big Pharma and Big Vitamin are pushing stuff out there without a lot of science by just just throwing stuff together. If it doesn’t sell, then they hire some branding agency or somebody to sell it for them. 

Our methodology is CytoSolve®, a disruptive but new methodology that is going to revolutionize the whole world through health discoveries. One result is giving an overall architecture of joint pain, about the combination discovered.

Using this new approach, how we can actually identify the synergistic effects of these compounds. There is a paper titled “In silico modeling and quantification of synergistic effects of multi combination compounds. 

Case study the attenuation of joint pain, using a combination of phytonutrients.” This paper really speaks to the fact that we have a methodology to apply to a combination that we actually came up with, for joint pain.

mV25 is a product made with CytoSolve®, a revolution of health.   

CytoSolve® was really developed out of the mission to really revolutionize health, be it therapeutics, nutraceuticals and functional foods. There is a need due to the current way that Big Pharma works in the pharmaceutical world of therapeutics. 

They have a compound that takes about 13 years to figure out, and that is very time consuming, which is why pharmaceutical companies have been losing money. The revolution is products like mV25™.

Dr.Shiva shares CytoSolve® and the Open Science Institute. The projects, stages, and out of the efforts mV25™ emerged from this.

Open Science Institute has more info at vashiva.com, and allows us to educate everyone. CytoSolve® has the ability to take lots of compounds. And supplements don’t have just one compound and run it through the engine and figure out if things work or not.

CytoSolve® was working on many, many different projects. The first one that is there is about joint health, in this project, we understood the molecular underpinnings of what constitutes joint health, how those molecular mechanics go, and how these undergo dysfunction and create disease like osteoarthritis. 

Having modeled those molecular mechanisms and discovered new combinations that can help with the indications like joint pain and inflammation. The first stage is understanding the molecular architectures or what would you call a systems architecture for that particular indication.

Next is the publication, in-silico modeling and then the screening of compounds. Which means we have looked at all available natural ingredients, and understand whether those ingredients are actually having any beneficial effect on improving joint health.

mV25™ is a product that emerged out of this, and many other developments in men’s health, brain health, etc. 

The framework of Systems architecture of joint pain and identifying the molecular mechanisms that affect the joints for osteoarthritis. The different biomarkers of chemicals that increase when you have pain and inflammation.

 Developing the System’s architecture of pain and inflammation at the molecular level by mapping out all the tissues that are in the knees as well as particular types of cells. 20,000 papers written out there, and among those 5,000, were found to be decent papers, relative to humans. 

We extracted all of the chemical reactions, mapped it out and built what we call an architecture. It’s like reverse engineering, 

This collaboration identifies the molecular mechanisms that are affecting the disease that affects the joints for osteoarthritis. What tissues are involved in the knee like the joint capsule, articular cartilage, meniscus, patella, synovial membrane, fat pad and the subchondral bone. 

The cartilage has one type of cell called Chondrocytes, whenever the cell is getting affected there are these chemical entities called ligands, that land on the surface of the cell, and then they start a cascade of chemical reactions, which form or contribute towards a function of a particular organ. 

One of the main cytokines that is implicated in osteoarthritis is called IL-1b. That molecule actually affects so many other so many of these molecules within the chondrocytes, and those molecules actually determine the fate of what is going to happen to your cartilage. 

One of the key molecules called MMP 13, this is a protein molecule that degrades the cartilage by initiating dozens of chemical reactions that lead to what we call a catabolic effect. Mapping out the particular pathways that are involved in pain and inflammation, another one of them is called COX-2 synthesis.

IL-1b lands on the receptor, the IL-1 receptor, and that leads to three pathways. One is p38, another is JNK2, while JNK1, which gives you MEK, and ERK which leads have the expression of COX-2. 

NK2 actually suppresses it with the whole being an intelligent system. It produces COX-2, but nature has a way to also suppress it, because you don’t want too much.

The next chemical is PGE2, which is part of this pathway called the Arachidonic acid metabolic pathway. In the cell membrane a series of chemical reactions to the Arachidonic acid takes place to make PGE2. That’s variable number two, that you need to lower if you want to reduce pain. 

Variable number three is TRPV1, a calcium channel. This is a receptor that is found on several of these cells, including the nerve cells. With expression of PGE2, as it lands on the cell surface, it initiates a cascade of reaction that leads to activation of the TRPV1. 

When you have high levels of pain, you have high levels of TRPV1, while PGE2 and COX-2 is really about inflammation. That’s variable number three.

The fourth biomarker, the fourth variable is CGRP, and when you have the overexpression of TRPV1 more of those channels on the cell surfaces, where once they get activated, calcium comes in from outside to inside. 

That initiates a series of reactions leading to the production of this neuropeptide called CGRP, which is what conveys pain to the brain.

The final biomarker, ROS, oxidative stress when your body is undergoing rusting. Pathways for every chemical reaction basically produces Reactive Oxygen Species, which are various types of things, one being H2O2.

Bioflavonoid combinations of mV25™ ingredients, and the alchemy for optimum health from compounds found in foods that affect the pain biomarkers in osteoarthritis.

Studies that looked at effective apigenin and hesperidin, which are bioflavonoids, playing roles as powerful anti-inflammatories. In mV25™ we’ve found a combination of two ingredients that come from parsley and bitter orange and in a very powerful way combine these to hit all those four pathways, which affect all those five biomarkers. 

That’s the alchemy of the traditional medicine healers 1000s of years ago in India. They had a knowledge of particular combinations that really comes down to dosage. How much you can really have or sometimes you might need only small amounts of things to have an effect.

It’s all about dose, and with mV25™ what we’re trying to do here is figure out the right dosage of these two combinations that will block these five different variables.

CytoSolve’s® potent combinations and quantification of synergistic effects for mV25™. Examples of antagonistic, additive, and synergistic effects based on dosage.

Using CytoSolve®, we mathematically modeled all these concepts of synergy, additive and antagonistic. Where the best way to think about something being antagonistic is you take compound A and compound B and you put them together and they annihilate each other.

This happens in bodybuilding. People drink a lot of caffeine and then  take arginine. Arginine will increase nitric oxide, but caffeine actually lowers it. Also, medications like the blood thinners, have adverse effects with the other compounds. 

They advise against combining blood thinners with certain medications or alcohol as it can have adverse effects with any of the heart medications or even the mood stabilizers as well.

Additive effect is you can take compound A and compound B individually, but the question is what happens when you take both of these together? If it brings it to a desirable level, that’s called an additive effect. 

Ginger and curcumin will bring down inflammation alone but if I’ve mixed them together, and it’s within a range that is an additive effect.

There’s something even more powerful if you take compound A and compound B, and it’s not in the additive range, but it actually brings it down even lower, which would mean the whole is greater than the sum of the parts.

This is something we call the synergistic effect, we took this combination of those compounds, and in testing if one of the ingredients, like apigenin the pain went down. Then if we just give hesperidin it will go down too, but when we give the combination at the right dosage it comes down an amazing seven times further. 

PGE2, which is the variable that is involved in the actual discomfort. That’s when you have swelling and pain and inflammation going on, apigenin brings it down and hesperidin does around the same. 

Then combine them and that brings levels down. This combination is additive, but it’s not as powerful as a synergistic effect. 

TRPV1, which is involved in the actual creation of pain, and when apigenin as well as hesperidin effect TRPV1 numbers will go down. When you give the combination of the two at the correct dosage the effect becomes synergistic. 

CGRP which is the next variable of pain, apigenin brings the levels lower and alone hesperidin has a lowering effect, but the combination, the synergy brings levels down about 10,000 times better than each one taken individually.

For reactive oxygen stress (ROS) the control level is the same when apigenin is there while hesperidin will bring levels down. While together the combination is also outside of the additive range making it synergistic.


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