The Story of the Mitochondria and Astaxanthin
by John Carberry
The questions we are seeking to answer, the problem to be solved, is the sudden rise during the past several decades of diseases which are taking an enormous toll on life expectancy and quality of life. Unfortunately, not all medical challenges can be solved with drugs and intervention, some must be solved with profound understanding of who we are and how we evolved. It comes down to actually understanding how our civilization evolved from our earlier prehistorical culture which included habits and traditions which fit like a perfect puzzle piece into a cogent picture.
One of the most defining features of being human is our self-awareness and deep-seated desires to understand who and why we are, where we come from, and even where we are going. This is all about what we will call civilization.
Civilization is the culmination of all our knowledge, intellectual structures and achievements, the arts, our customs, inventions, organization, development, infrastructure, progression, it is the seen in our culture and society.
Society is of course the collection of people, and it is defined by what we call culture. This includes knowledge, customs, arts, institutions, habits, traditions.
As we seek to understand who and why we are and where we come from, we desire also to optimize our lives, its length, health, its pleasure, comfort and power to provide us with self-actualization. The scope of time and depth of knowledge we need to examine in this journey turns out to be a few billion years.
We are programmed through an evolutionary development over billions of years to mediate the balances in our biology mostly through diet. If we consume the right diet, we are programmed to be healthy, reproductively effective, even long lived. The sea’s euphotic zone is the most productive, largest and over time, the most stable food pyramid on earth and has been for a very long time. In this food pyramid Bowhead wales live nearly 300 years, Icelandic sharks 600 years, Rockfish more than 200 years without cancer or disease and they are eating their perfect evolutionary diet.
Within civilization and culture, we have to account for customs and habits and traditions, many of which were programmed into our biology during these few billion years. Our ability to reprogram, to evolve, our cultural habits and traditions is far more powerful and can move far faster than our biological evolution. So as we question the sudden rise in the past few decades of several serious diseases which are shortening our lives and diminishing the quality of our lives, we must reconcile this difference in the time frames of biological and cultural evolution. How important is this? These few curves answer this question and we propose here that we have solutions for mitigating these:
The History of the Evolution of Life on Earth is Integral to Human Health and Wellbeing:
I am 65 years old, finished an undergraduate degree in 1976, and have participated during the past 20 years in the most exciting times, by orders of magnitude in the history of civilization, for learning and intellectual expansion in human knowledge. I believe most all of what we know today we have learned in the past few decades. If one does not work hard to understand this rise of knowledge and integrate all of it into one’s models, one is quite frankly living in a prior age. We do understand now that there are several ages in the evolution of life on earth. And how recently we learned some of this is close to incredible:
In 1977 Dr. Carl Woese introduced the idea that archaebacteria were separate from bacteria. Essentially, he proposed that the traditional model of prokaryotes, which included bacteria, and eukaryotes, which included complex live based on cells with organelles and a nucleus were proceeded by archaea. There are accounts that he was laughed out of the meeting.
In 1996 Dr. Woese published the genome for an archaea. Later he showed that archaebacteria were more closely related to eukaryotes than bacteria. And he suggested that evolution in these earlier days was not competitive, there was a lot of horizontal genetic migration and Darwinian evolution took precedence when later complex eukaryote life form arose.
Archaea evolved and lived on earth during a time when prokaryotes and eukaryotes could not have lived: earth was warm, it was acidic, salty and anaerobic. These are the conditions that archaea favored.
Evolution in our universe is a complex story and has time domains. Some tell the story of the universe, some the story of life on earth, some of humans. They are interdependent:
The Great oxidative event is a major event in the history of life on earth. O2 build-up in the Earth's atmosphere. Red and green lines represent the range of the estimates while time is measured in billions of years ago (Ga). Stage 1 (3.85–2.45 Ga): Practically no O2 in the atmosphere. The oceans were also largely anoxic with the possible exception of O2 in the shallow oceans. Stage 2 (2.45–1.85 Ga): O2 produced, rising to values of 0.02 and 0.04 atm, but absorbed in oceans and seabed rock. Stage 3 (1.85–0.85 Ga): O2 starts to gas out of the oceans but is absorbed by land surfaces. No significant change in oxygen level. Stages 4 and 5 (0.85 Ga–present): Other O2 reservoirs filled; gas accumulates in atmosphere. (https://en.wikipedia.org/wiki/Great_Oxidation_Event#/media/File:Oxygenation-atm-2.svg)
Where did this oxygen come from? Oxygen was first produced and accumulated in the seas by prokaryotic life forms, and then later by eukaryotic organisms in the ocean through photosynthesis. These organisms carried out photosynthesis more efficiently and produced oxygen as a waste product. The first oxygen-producing cyanobacteria would likely have arisen before the great oxidation event.
Archaea did not much care for or tolerate oxygen. As the oxygen content in the seas rose, the opportunity for eukaryotes to evolve and exploit that oxygen evolved. We understand that eukaryotes evolved between 2.1 billion and 1.6 billion years ago and they needed to process oxygen for the purpose of making energy. We understand that archaea evolved into the mitochondria through a process called endosymbiosis. So we took an organism that did not much like oxygen and we gave it a function that involved processing oxygen.
The mitochondrion is part of our respirating process. It takes sugars, glucose for example, and half an oxygen molecule, from O2 it takes an oxygen singlet, and uses COQ10 as an enzyme to convert two adenosine di phosphate (ADP) molecules into two adenosine tri phosphate (ATP) molecules and two free extra electrons. In this handling of oxygen singlets some get lost. They become reactive oxidative species (ROS). For instance, hydrogen peroxide H2O2, is a reactive oxidative species. Other ROS include names such as Super oxide dismutase, Oxygen singlet, hydroxyl radical, super oxide, peroxides, alpha oxides and others. We needed mitochondria to make energy, but we needed to mitigate ROS. So from this time starting 2.1 billion years ago till the large rise of photosynthesizing algae 1.5 billion years ago, this battle with ROS has been a dominating theme in biology:
So how did evolutionary biology mitigate the ROS, and when did it start to effectively manage ROS? The first observation I would make is that in looking at the evolutionary tree for carotenoids it is astaxanthin that is in the food pyramid where it is highly likely that most all evolving live in the seas from about 2.1 billion years ago till about 500 million years ago, where most all of life was evolving, astaxanthin was the only one highly available. And it was made in small quantities by marine algae, about 1 mg per gram, but was concentrated in the food chain.
It is currently thought that photosynthesis started in archaea well before the great oxidation event. This would have included photosynthetic pigments, but this photosynthesis was anaerobic and probably could not tolerate oxygen. Most evolutionary models describing evolution between 1.5 and 2.4 billion years ago use horizontal development models and endosymbiosis is a major theme.
With the advent of the great oxidation event, archaea evolved through endosymbiosis to become mitochondria, and new carotenoids evolved which are part of the photosynthetic evolution and part of the chlorophyll story but have so many other functions in virtually all eukaryotes. In doing so they took up antioxidant functions.
We know that copepods very efficiently assemble carotenoids into astaxanthin. Copepods are near the top of the food chain in the euphotic zone, they eat algae, and make a lot of astaxanthin. From phylogenetic profiles we can trace the current 12,800 species of copepods to a point of divergence about 480 million years ago. Generally, they are believed to have been extent for about 800 million years ago functioning not unlike they function today.
So of all the candidates to fill a role as a nearly universal metabolic antioxidant, astaxanthin from marine algae and copepods are candidate number one.
The mass transfer between ADP and ATP in 24 hours for a 70-kilogram human is about 70 kilograms and will use 700 grams of oxygen. As much as 2% of the processed oxygen has to be mitigated from acting as ROS and damaging the mitochondria, the COQ 10, the histone on the DNA/RNA of the mitochondria, mitigating energy production and traveling out towards the cell plasma membrane and interfering with molecular chemistry processes down stream from there, including eicosanoid cascades. We die in four minutes without oxygen.
The rise of autism, Alzheimer’s, Parkinson’s, Autoimmune Diseases, cancer, lymphoma, and aging are all associated today with well characterized decline in mitochondrial expression, function and efficiency. Astaxanthin is uniquely designed within evolutionary history going back 1.5 billion years to 2.4 billion years ago, or more, to manage the threat to all of these functions from ROS. In our evolution it has always been there, it has always performed this function, and must always be there.
So what is astaxanthin? It’s chemical formula is C40H52O4. It has several characteristic features:
- It has a conjugated backbone where every carbon has one double bond to another carbon, a single bond to the next carbon and a bond to a hydrogen atom. This makes it very hydrophobic and a very strong antioxidant.
- There are two rings on either side, with a double oxygen bond and a hydroxyl
- It has been measured at about 60 in liposomes and 10-20 nm in micelles
- The cell plasma membrane is about 2-10 nm. The cell walls between 5 and 60 nm
- The astaxanthin molecule is composed with about 6 nm long
- The rings tend to be hydrophilic
- The backbone very hydrophobic
- The blood and cell cytoplasm are mostly water
- So astaxanthin is ideally suited to take up semi permeant to permeant residence in the cell membranes and mitochondrial membranes
When astaxanthin rises in the natural food pyramid from algae’s and copepods the astaxanthin is contained in a lipid rich mixture and is highly bioavailable. However the content is not so highly concentrated. For instance if we consume about 200 grams of wild Atlantic Salmon a day we will get the amount of astaxanthin we need to be healthy. And harvesting marine algae and copepods to obtain astaxanthin is not practical or economic.
The synthetic and yeast sources astaxanthin are different stereoisomers and not molecularly effective as needed.
So the world and industry turned to an algae called Haematococcus pluvialis, a fresh water algae that at the end of its growth cycle, just before a long hibernation converts a large amount of its bio mass to astaxanthin, as high as 7%. However, the purpose of this conversion to astaxanthin is unlike the purpose and form of most any other carotenoid: the purpose is to make itself indigestible, un-bioavailable, hardened ad protected from UV. In the picture below, on the left is a TEM of the algae in the green state, and on the right in the encysted state. The cysts are about 60 microns in diameter and filled with astaxanthin literally tied up in physical knots. Its purpose is to survive hibernation, probable ingestion and survival to grow in the next season.
During the rise of our civilization our food was industrialized, most of the astaxanthin was removed from our diets and so many highly oxidizing foods were added to our diet. But it turns out we can formulate astaxanthin from Haematococcus pluvialis (HP) and make it highly bioavailable and solve this most critical needs and problems.
From Nanoliposomes as Vehicles for Astaxanthin: Characterization, In Vitro Release Evaluation and Structure Li Pan et al in 29 September 2018; Accepted: 25 October 2018; Published: 30 October 2018 reported the bio availability of a lipid rich nano emulsion of astaxanthin theorizing they were making liposomes.
Figure 5. In vitro release of astaxanthin from astaxanthin solution and nanoliposomes in PBS (pH 7.4) at 37 ◦C. Data are represented as the mean ± standard deviation (n = 3).
The geography we are addressing in mitigating ROS are the cell and mitochondrial membranes
Sustainable Nutrition’s technology takes the HP algae and processes it with a very low cost process to make it into a nano emulsion where the high lipid content of the HP is nano emulsified with those lipids to set up making micelles and liposomes so to make an otherwise unbioavailable substance highly bioavailable. This takes very high shear temperature, a strong solvent content, low temperatures to make an oleoresin which can now be made highly bioavailable.
Why is astaxanthin so important, so critical? Some observations:
Cells will not divide unless they have enough energy. This means an inventory of ATP, never large, and an ability to make ATP on demand. Here is a schematic of this process:
ATP management within the cell. Schematic representation of mechanisms of ATP synthesis and storage inside the cell. Glycolysis is represented in the yellow and blue boxes, the TCA cycle by the green circle, and oxidative phosphorylation in the orange box. Reduction of pyruvate to lactate is represented inside the red dotted rectangle. Hypothetical contacts between ATP storage vesicles and mitochondria, with preferential ATP transfer, are shown within the red dotted circle
- 2)This means growth and development require adequate supplies of energy which are unlikely to be available without the mitigating power of astaxanthin.
- 3)Most metabolic pathways include complex multistage molecular chemistry which require small prooxidant triggers and protection from strong ROS, as well as great amounts of energy. For instance, using taurine, selenium, or COQ 10 as anti-oxidants is tremendously counter productive since they are poor anti-oxidants compared to astaxanthin and have specific critical necessary metabolic roles. For instance, while astaxanthin has a ORAC value of 2.8 million units, COQ10 which is necessary as an enzyme in the mitochondria to make ATP is 3000 units.
Sustainable Aquatics invented and developed this technology and these insights in order to optimize the production of fish. Fish will not make eggs, big eggs or a lot of eggs unless they have enough energy. Larval fish will not develop through metamorphosis in time to be healthy, achieve their needed metabolic, endocrinal, nervous and other systems in time to compete unless their cells can divide rapidly and they have enough energy. Using our patented technology, which is industrial, has low CAPEX and Low OPEX and very high yield we have been able to show far superior ability to get astaxanthin from HP into animal tissue: here the unextracted is cracked HP cells, the extracted is from Super Critical Carbon Dioxide extraction (SCCO2) and Oleoresin is SN’s lipid rich nano emulsified astaxanthin:
And then we fed it to brood stock for blue tangs, this is Dory from Disney’s movie and fed identical feeds but one with SCCO2 astaxanthin, and the other on the left our lipid rich nano emulsified astaxanthin:
Then we took a batch of clown fish and split it in half. We fed half the cohort rotifers, a live feed, with normal algae, Tetraselmis, and we supplanted the other rotifers with a small amount of our lipid rich nano emulsified astaxanthin:
Clearly the astaxanthin in the fish fed on the right had adequate energy to grow as they needed and became naturally colorful as well.
- So part of our civilization’s evolution was the industrialization of food. At the end of the day, civilization’s nature is its knowledge content and the network capital utility of its knowledge.
- For instance, we now understand the relationship between mitochondrial function and autism. There are a wide range of genetic precursors in the etiology of compromised mitochondrial functional profiles, but they all contribute to the rise of autism.
- In the US a woman preparing to conceive has a .02 chance of having an autistic child. Fifty years ago it was about .001. A woman who has delivered an autistic child then as a 20% chance of a second autistic child. It is proposed that taking 12 mg of a lipid rich nano emulsified astaxanthin could change those odds.
- Astaxanthin passes easily through the blood brain barrier. It is probable it can preclude, mitigate or even cure a wide range of cognitive diseases.
- Autoimmune diseases are the result of the failure of immune system and the eicosanoid system to address problems which require a lot of energy and freedom of metabolic pathways to function optimally. Astaxanthin has a role here.
- Aquaculture is raising animals that in nature consume a lot of astaxanthin. Clearly, they need it to make good eggs and get through metamorphosis. If fish do not get through metamorphosis as programmed, they will be compromised for a life time.
- Fifty years ago broiler egg hatch rate was 98%. Today it is 78%. Astaxanthin can cure this.
- Aging studies today correlate symptoms of aging with mitochondrial decline. But astaxanthin ca cure, mitigate and deliver great effects here.
- All we need is process with hat makes a lipid rich nano emulsified astaxanthin. That is our invention.
- We are the product of a few billion years of evolution, with a great deal of context. Our mitochondria and its needs and management requires astaxanthin and astaxanthin was always there in our evolution.