*7.1. Dosing*

Human clinical studies have used oral astaxanthin in a dose that ranges from 4 mg up to 100 mg/day, given from a one off dose up to durations of one-year (Table 2). 


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## *7.2. Bioavailability*

Astaxanthin bioavailability from the marine environment was assessed in a randomised double blind trial in 28 volunteers [83]. Participants were given either 250 g of wild salmon or aquaculture salmon (5 μg/g) to eat. Wild salmon ingest astaxanthin naturally from krill whereas aquacultured salmon acquire it from fish that are fed astaxanthin that might be derived from a synthetic source. Plasma levels of astaxanthin were higher at 3, 6, 10 and 14 days during ingestion of the aquacultured compared with the wild salmon. Plasma levels of the (3-*S*, 3<sup>ȝ</sup>-S) isomer of astaxanthin appeared at higher levels than its proportionate level in the flesh of the salmon. This suggests that isomers of astaxanthin might have different bioavailability. The plasma isomers of astaxanthin have also been studied after ingestion of single oral dose of 10mg and also 100 mg over four-weeks. Astaxanthin plasma elimination half-life was 52 (SD 40) h and there was a non-linear dose response and selective absorption of z-isomers [79].

## *7.3. Safety*

The safety of astaxanthin administered orally was assessed in a double-blind, randomised placebo-controlled trial undertaken in healthy adults [78]. Volunteers took either 6 mg/day of astaxanthin or placebo for eight-weeks. BP and biochemistry measured after four and eight weeks of therapy revealed no significant differences in these parameters between treatment and placebo groups and these did not differ from baseline. The authors concluded that healthy adults could safely consume 6 mg/day of astaxanthin derived from a *Haematococcus pluvialis* algal extract. Measuring whole blood transit time in 20 healthy males was used to assess the effects of astaxanthin on blood rheology in humans. Six milligrams of oral astaxanthin per day for ten days improved blood rheology as evidenced by decreased whole blood transit time [82]. Escalating concentrations of astaxanthin were tested *in vitro* with blood taken from volunteers, 8 of whom were taking asprin and 12 who were not [85]. Even supra-therapeutic concentrations of astaxanthin had no adverse effects on indices of platelet, coagulation and fibrinolytic function. These results support the safety profile of astaxanthin for future clinical trials. No significant side effects have been reported so far in published human studies in which astaxanthin was administered to humans. 

## *7.4. Oxidative Stress and Inflammation*

Oral supplementation with astaxanthin in studies in healthy human volunteers and patients with reflux oesophagitis demonstrated a significant reduction in oxidative stress, hyperlipidemia and biomarkers of inflammation [70,80,86]. In a study involving 24 healthy volunteers who ingested astaxanthin in doses from 1.8 to 21.6 mg/day for two weeks, LDL lag time, as a measure of susceptibility of LDL to oxidation, was significantly greater in astaxanthin treated participants indicating inhibition of the oxidation of LDL [70]. Plasma levels of 12- and 15-hydroxy fatty acids were significantly reduced in 40 healthy non-smoking Finnish males given astaxanthin [80] suggesting astaxanthin decreased the oxidation of fatty acids [80]. The effects of dietary astaxanthin in doses of  0, 2 or 8 mg/day, over 8 weeks, on oxidative stress and inflammation were investigated in a double blind study in 14 healthy females [84]. Although these participants did not have oxidative stress or inflammation those taking 2 mg/day had lower CRP at week eight. There was also a decrease in DNA damage measured using plasma 8-hydroxy-2ȝ-deoxyguanosine after week four in those taking astaxanthin. Astaxanthin therefore appears safe, bioavailable when given orally and is suitable for further investigation in humans. 
