History of Astaxanthin
Born from humble origins, astaxanthin is perhaps one of my favorite substances.
A byproduct of a nearly ubiquitous alga, it's created during times of stress, but it imparts a calming effect on biological systems... including our own. I consider it an antidote to anger: calming, ubiquitous, and subtle.
The story begins in the algae of a birdbath, in ephemeral rain puddles, and indeed, in most small, temporary bodies of freshwater. The biflagellate, single-celled green bacterium, Haematococcus pluvialis , is the main producer of astaxanthin, so we will focus on this tiny creature. This single-celled organism lives all over the world, primarily in Europe, Africa, North America, and parts of India, but always in small bodies of water. It has been found in brackish water on coastlines, in freshwater basins filled with melting snow, in dried-up springs in Bulgaria, and even in fishponds in Romania.
Normally, this single-celled organism is green, as you've probably guessed from observing algae-covered birdbaths, and it's quite resilient. However, what's truly remarkable is what the algae does when it gets "angry." Under unfavorable or stressful conditions, the macrozooids lose their flagella and swell. They then begin producing astaxanthin in tiny lipid droplets that accumulate in the cytoplasm. These droplets turn the cells a bright red, and the cell can now withstand the extreme environmental conditions that caused its initial stress. Somehow, this miraculous red substance manages to protect the cell.
A few red droplets in a single-celled organism might not seem to have much of an impact on a global scale, but surprisingly, they do. This red substance enters the food chain and becomes the basis for almost everything red we see in crustaceans, fish, and birds. It's the red in salmon, lobsters, crabs, and shrimp. It's in the feathers of roseate spoonbills. It's in the eyes of quail. And, most importantly, it reaches us.
Within our bodies, astaxanthin does the same thing it does in the algae from which it originates. Cellular stress in algae can range from a high-salinity environment and nitrogen deficiency to elevated temperatures. Stress in a human cell can be imagined through many of the things we've already discussed, such as oxidative damage and free radicals. Astaxanthin works by calming an irritated system and promoting cell survival. It neutralizes free radicals, blocks damage caused by oxidative stress, and acts as an anti-inflammatory. It can alleviate pre-existing trauma and prevent new damage from occurring.
In terms of aging, it can repair some of the accumulated cell damage and help control cell survival in the future.
What is astaxanthin?
Astaxanthin is a xanthophyll carotenoid, which basically means a plant pigment that is usually very colorful. Other substances in this family include carotenes, which are yellow to orange; beta-carotenes, which are green to yellow; lutein, which is yellow; zeaxanthin, which makes Indian corn yellow; and lycopene, which makes tomatoes red. Astaxanthin is also red, but it's a bright red; intensely red. As I mentioned, it's the substance that makes lobsters and crabs red.
The other thing that makes this molecule different is its structure. Formally called 3,3'-dihydroxybeta-beta-carotene-4,4'-dione , or C40H52O4 , it's a long molecule consisting of a carbon chain in the center with an ionone ring at each end; essentially, it resembles a simple chain bracelet with a circular clasp. The conjugated double bonds in the center of the molecule are responsible for the red color, but, well, that's just a geeky detail.
What makes this molecule so special?
The simple fact that it is capable of doing so many incredible and positive things to the body without any real side effects.
Astaxanthin is many things:
Mitochondria / Energy systems: Antioxidant and free radical scavenger.
What's the difference, you ask? This is a key category for astaxanthin, so I'm going to go into a little more detail here.
An antioxidant is a molecule that inhibits the oxidation of other molecules. Oxidation is a chemical reaction that can produce free radicals, leading to chain reactions that can damage cells.
On the other hand, a free radical scavenger is a molecule capable of destroying free radicals. The term 'free radical' refers to a molecule that has one or more unpaired electrons. This makes them very unstable, and they move through the bloodstream, stealing electrons from other cells or donating their unpaired electrons.
Astaxanthin “acts as a safeguard against oxidative damage through several mechanisms, including singlet oxygen capture; scavenging of free radicals to prevent chain reactions; preservation of membrane structure by inhibiting lipid peroxidation; enhancement of immune system function and regulation of gene expression.”
Remember that free radicals and reactive oxygen species are produced by normal cellular functions, and most are handled by the body's own natural defenses.
However, uncontrolled free radicals react with proteins, lipids, and DNA to cause significant molecular damage and aging.
When our astaxanthin molecule reaches an individual cell (we'll discuss transport later), it is able to incorporate itself into both the cell membrane and the mitochondrial membrane. The molecule inserts itself directly into the lipid bilayers and spans the entire membrane.
Called transmembrane orientation, this privileged location allows the molecule to work its magic in various subcellular components. As a direct result, astaxanthin is a far more potent free radical scavenger (ROS) than its molecular cousins. It is 200 times more potent than other polyphenols, 150 times more potent than anthocyanins, 75 times more potent than alpha-lipoic acid, 550 times more potent than vitamin E, 54 times more potent than beta-carotene, 6,000 times more potent than vitamin C, and 800 times more potent than coenzyme Q.
When comparing antioxidant capacities, the results are essentially the same. Astaxanthin is 10 times more potent than lutein and zeaxanthin, 14 times more potent than vitamin E, 54 times more potent than beta-carotene, 65 times more potent than vitamin C, and 100 times more potent than alpha-tocopherol. Astaxanthin is simply more powerful than its competitors.
Astaxanthin is quite unique; it can accept or donate protons, but unlike many other substances, it does not become a pro-oxidant.
Therefore, any potential damage inflicted by free radicals is significantly reduced.
As an interesting example, one study measured the effects of astaxanthin on normal women and their DNA.
Before explaining the study, it's interesting to note that DNA damage can actually be measured. Specifically, we quantified the amount of 8-hydroxy-2-deoxyguanosine in plasma.
Unfortunately, constant DNA damage is a fact, and at least knowledge is power; therefore, we can begin to do something about it.
However, in 2010, a study analyzed healthy women around 21.5 years old who took a placebo, 2 mg, or 8 mg/day of astaxanthin for 8 weeks. Surprisingly, both doses of astaxanthin significantly reduced the rate of DNA breakdown.
An important message here is that even people in their twenties are experiencing measurable DNA damage. They're already aging; they just don't know it.
Seeking further evidence of astaxanthin's power to combat free radicals, eye tissues in diabetic rats were examined for evidence of hyperglycemia-induced oxidative stress damage and its reversibility.
Not only do high glucose levels increase the production of oxygen free radicals, but they also deplete cellular antioxidant defenses. As expected, significant damage to the retina and surrounding eye tissues was observed in the control group. In comparison, the addition of astaxanthin to their diet, at various concentrations, was extremely beneficial.
“The eye tissues of rats treated with astaxanthin had significantly reduced levels of oxidative stress mediators (8-hydroxy-2-deoxyguanosine, nitrotyrosine, and acrolein) and inflammatory mediators… and increased levels of antioxidant enzymes.”
Therefore, it was clearly demonstrated that the addition of astaxanthin had a protective effect and helped to preserve the architecture and function of the ocular tissues.
“Astaxanthin prevents the initiation of cancer by alleviating oxidative damage to DNA.”
“Astaxanthin is well known as a powerful free radical scavenger and an excellent anti-inflammatory agent that suppresses the expression of pro-inflammatory cytokines and chemokines.”
“It is worth mentioning that astaxanthin can act as a safeguard against oxidative damage through various mechanisms, such as singlet oxygen capture, radical scavenging, inhibition of lipid peroxidation, and regulation of gene expression related to oxidative stress.”
What about oxidative stress in people?
Overweight and obese individuals are believed to be particularly vulnerable to oxidative stress, making them good test subjects. To examine this, a 2011 study measured stress markers (malondialdehyde and isoprostanes) and antioxidant capacity markers (superoxide dismutase and total antioxidant capacity). As expected, the untreated obese population had higher stress markers and lower antioxidant capacity than normal-weight individuals. After three weeks of astaxanthin therapy in the obese population, remarkably, all stress markers and antioxidant capacity measures normalized—quite impressive, especially after just a couple of weeks.
In addition to its own inherent antioxidant activity, astaxanthin also stimulates the body's natural defenses and increases cellular levels of catalase, superoxide dismutase, and peroxidase. At least, this is known to occur in rats and rabbits.
"Astaxanthin is not only able to protect against free radicals on its own, it also stimulates the production of the antioxidant enzymes catalase, superoxide dismutase and peroxidase."
As Wu noted in 2015, astaxanthin can act as a safeguard through a variety of mechanisms, such as "singlet oxygen capture, radical scavenging, inhibition of lipid peroxidation, and regulation of gene expression related to oxidative stress."
To reinforce the idea that astaxanthin is good for mitochondria, I offer even more evidence.
Unfortunately, studies on the effects of astaxanthin specifically on mitochondria are somewhat rare. However, there is one large study involving beagles.
Both young and old beagles were fed astaxanthin for 16 weeks, and several things were discovered:
- Astaxanthin suppressed DNA damage; a lot in old dogs and a little in young dogs.
- Mitochondrial mass increased in geriatric dogs.
- Astaxanthin increased ATP or energy production by 12% to 14% in both young and old dogs.
Immune systems / Safety: Anti-inflammatory properties
The evidence for this quality is quite substantial, and we will examine it from the cellular level upwards.
In 2012, a human cell line was bathed in astaxanthin in a warm, comfortable laboratory. The magic substance inhibited ROS-induced NF-κB activation, which suppressed the production of IL-1β, IL-6, and TNF-α. If you recall from the chapter on inflammation, these cytokines can cause significant damage both locally and systemically. Limiting this pathway is, therefore, a good thing.
To further support this, human microglial brain cells, also in a comfortable environment, were perturbed with the addition of LPS (lipopolysaccharides), which incite the production of inflammatory factors, especially IL-6. In this 2010 study, the addition of astaxanthin to the culture medium suppressed the production of IL-6 and NF-κB.
Convinced that isolated cells benefited from astaxanthin, we turned our attention to real mammals.
Knowing that diabetes can wreak havoc throughout the body, but especially in the brain, researchers tried to improve outcomes in diabetic rats treated with astaxanthin.
- After five days of treatment with astaxanthin, the neurocognitive skills of diabetic rats were actually better than those of non-diabetic rats.
- The researchers observed the brains of the treated rats: inflammatory markers such as NF-κβ, TNF-α, IL-1B and IL-6 in the cerebral cortex and hippocampus improved markedly.
- In addition, astaxanthin appeared to help control blood sugar.
In another interesting brain study, rats were pretreated with astaxanthin and then subjected to a subarachnoid hemorrhage. Normally, blood in the brain is extremely inflammatory.
- Astaxanthin reduced neutrophil infiltration.
- It suppressed NF-κβ activity.
- It decreased the levels of IL-1β, TNF and ICAM-1 (intercellular adhesion molecule).
The treatment dramatically reversed brain inflammation, reducing secondary neuronal damage, protecting the blood-brain barrier, and preserving brain function.
Researchers love astaxanthin; they love torturing rats and saving brains. As a result, there is a wealth of research confirming the supplement's protective effect on rat brains.
Therefore, I will summarize the key message: Astaxanthin can cross the blood-brain barrier, enter neural tissue, and work its magic through a multitude of properties.
The next step in examining inflammation is to look at the grandfather of all inflammation: sepsis.
Sepsis is a whole-body phenomenon in which inflammation caused by a triggering factor leads to systemic damage. It is a life-threatening complication in which chemicals released into the bloodstream to fight infection trigger inflammatory responses throughout the body, causing more harm than good.
To test the protective effects of astaxanthin, rats were given a relatively high dose for 7 days and then subjected to a procedure that induced sepsis.
- Compared to untreated rats, astaxanthin reduced the systemic inflammatory response (lower TNF, IL-1β, IL-6).
- It relieved the damage to the organs.
- It reduced the peritoneal bacterial load.
- It improved the survival rate of the rats.
You may not care about the lives of these little septic rats, but you probably will if you ever find yourself in an ICU with a similar problem.