I’m going to try to pull together the research on the potential benefits and risks of higher Astaxanthin doses. Ideally we’d identify some biomarkers we can use to see if the compound is providing us the benefits we hope for, while allowing early identification of any of the negatives side effects.
If you have time, please search around on Pubmed and post additional information relevant to this compound. Obviously, top priority is for human clinical trials, and the longer the better.
Here is my start:
Potential Benefits of Astaxanthin:
In double-blind, randomized controlled trials (RCTs), astaxanthin lowered oxidative stress in overweight and obese subjects and in smokers. It blocked oxidative DNA damage, lowered C-reactive protein (CRP) and other inflammation biomarkers, and boosted immunity in the tuberculin skin test. Astaxanthin lowered triglycerides and raised HDL-cholesterol in another trial and improved blood flow in an experimental microcirculation model. It improved cognition in a small clinical trial and boosted proliferation and differentiation of cultured nerve stem cells. In several Japanese RCTs, astaxanthin improved visual acuity and eye accommodation. It improved reproductive performance in men and reflux symptoms in H. pylori patients. In preliminary trials it showed promise for sports performance (soccer). In cultured cells, astaxanthin protected the mitochondria against endogenous oxygen radicals, conserved their redox (antioxidant) capacity, and enhanced their energy production efficiency.
Astaxanthin has been reported to inhibit low-density lipoprotein (LDL) oxidation and to increase high-density lipoprotein (HDL)-cholesterol and adiponectin levels in clinical studies. Accumulating evidence suggests that astaxanthin could exert preventive actions against atherosclerotic cardiovascular disease (CVD) via its potential to improve oxidative stress, inflammation, lipid metabolism, and glucose metabolism.
LDL cholesterol and ApoB were significantly lower after treatment with astaxanthin, compared with the start of administration, whereas none of the lipid profiles was changed in the placebo group. At the baseline, all four biomarkers were not significantly different between the two groups. Compared with the placebo group, MDA and ISP were significantly lower, but TAC was significantly higher in the astaxanthin group at 12 weeks. These results suggest that supplementary astaxanthin has positive effects by improving the LDL cholesterol, ApoB, and oxidative stress biomarkers.
Long-term 1 mg ASTA/kg body weight (BW) supplementation in Wistar rats (for 45 days) significantly delayed time to exhaustion by 29% in a swimming test. ASTA supplementation increased scavenging/iron-chelating capacities (TEAC/FRAP) and limited exercise-induced iron overload and its related pro-oxidant effects in plasma of exercising animals. On the other hand, ASTA induced significant mitochondrial Mn-dependent superoxide dismutase and cytosolic glutathione peroxidase antioxidant responses in soleus muscles that, in turn, increased GSH content during exercise, limited oxidative stress, and delayed exhaustion.
Conclusions: our results suggest that ASTX may have preventive effects against diabetes and atherosclerosis and may be a novel complementary treatment option for the prevention of diabetes in healthy volunteers, including subjects with prediabetes, without adverse effects.
Owing to its ability to cross the blood‑brain barrier, astaxanthin has received attention for its protective effects against neurological disorders, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, cerebral ischemia/reperfusion, subarachnoid hemorrhage, traumatic brain injury, spinal cord injury, cognitive impairment and neuropathic pain. Previous studies on the neurological effects of astaxanthin are mostly based on animal models and cellular experiments. Thus, the biological effects of astaxanthin on humans and its underlying mechanisms are still not fully understood.
Potential Risks of Astaxanthin
Canthaxanthin Retinopathy
Not specific to Astaxanthin, but Canthaxanthin is another Carotenoid, and since there are issues with dosing Canthaxanthin at extremely high doses (10X to 20X higher than the 3grams/day Astaxanthin that is the human equivalent to what the NIA ITP is giving their mice) for long periods of time, it seems that there could be a small but possible risk of similar issues with Astaxanthin.
In high doses it seems Canthaxanthin can accumulate in the eye and cause crystals, which impair vision. When the person stops taking Canthaxanthin generally the crystals degrade / dissolve over time by themselves.
Apparently, some people take Canthaxanthin at high doses to get the desired change in skin color, this supplement is marketed as a “tanning supplement” because it gives people’s skin a brown/orange tint.
Canthaxanthin and other carotenoids locate in biological lipid membranes and based on their orientation and location can influence membrane properties such as permeability and fluidity. They are powerful antioxidants due to their radical scavenging and singlet oxygen-quenching properties [6]. However, in vitro studies have actually demonstrated prooxidant effects of carotenoids at higher concentrations [6]. In the setting of canthaxanthin retinopathy, it is thought that damage occurs at the level of the macular vascular system around areas of canthaxanthin-lipoprotein complex deposits, which comprise the visible crystals [7]. It is proposed that vascular dysfunction occurs due to aggregation of these complexes in vessel lipid layers, which modify and disrupt lipid membrane properties [7].
Incidence and prevalence are difficult to predict due to the generally asymptomatic course of canthaxanthin retinopathy. Some reports state an incidence between 12 and 14% [8, 9]. Harnois et al. [9] noted that crystal appearance follows a dose-dependent correlation, seen with 50% of patients ingesting a total dose of 37 g and with 100% ingesting greater than 60 g.
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Treatment for canthaxanthin retinopathy is immediate discontinuation of the drug as soon as crystals are identified, even if the patient is asymptomatic. Prognosis is very good with complete recovery occurring in the vast majority of patients. Hueber et al. [16] followed five patients for 16–24 years and no long-term adverse effects were found, and fluorescein angiography results were normal, although complete resolution of golden particle appearance took up to 20 years.
In summary, canthaxanthin retinal crystal deposition is a very common finding in patients with prolonged use of the drug. Symptomatic visual loss is less common and correlates with total dosage and possibly patient age. Even with profound visual loss, prognosis for improvement is very good with recognition and discontinuation of the drug.
Source Paper: Canthaxanthin Retinopathy with Visual Loss: A Case Report and Review
Related Paper: Canthaxanthin Retinopathy: Anatomic and Functional Reversibility | JAMA Ophthalmology | JAMA Network
Summary
So - there seems to be a small risk of the reversible condition similar to what is called Canthaxanthin Retinopathy. It is seen in humans who take 37 to 60 grams of Canthaxanthin (which is in the same family of molecules as astaxanthin).
However, the amount of astaxanthin that is being discussed is the human equivalent of the dosing used in the ITP Mouse Studies. The mice receive 4,000ppm of Astaxanthin. This is equivalent to about 3.6 grams/day (by our calculation) in human terms. This is still only 10% of the dosing of Canthaxanthin dosing levels that are seen to cause Canthaxanthin Retinopathy.
