*3.2. Astaxanthin and Cardiovascular Disease: Experimental Studies*

Astaxanthin has undergone investigation in a large number of experimental studies related to the cardiovascular and cerebrovascular systems. Only few studies have investigated the potential benefits of astaxanthin in human health and disease and most of these have been performed in healthy volunteers to assess dosing [26], bioavailability [27,28], safety [29], oxidative stress, and inflammation [26,30]. 

Studies conducted in healthy human volunteers have found significant reductions in oxidative stress, hyperlipidemia and inflammatory markers after astaxanthin oral supplementation. In particular, Cicero *et al.* [31] have demonstrated that food supplements for four weeks containing a combination of natural products such as berberine, policosanol, red yeast extracts, folic acid and astaxanthin could be a useful support to diet and life style changes to correct dyslipidemias and to reduce cardiovascular (CV) risk in 40 subjects with moderate mixed dyslipidemias. In this study total cholesterol (TC), 

LDL-C, high density lipoprotein cholesterol (HDL-C), non HDL-C, Apo-B, Apo-A, Lp(a) and triglycerides (TG) were measured before and at the end of treatments. Berberine and combinations of natural products (policosanol, red yeast extracts, folic acid and astaxanthin) significantly reduced TC (respectively by 16% and 20%), LDL-C (by 20% and 25%), Apo-B (by 15% and 29%) and TG (by 22% and 26%), and increased HDL-C (by 6.6% and 5.1%). Even Yoshida *et al.* [32] demonstrated in a randomized, placebo-controlled human study (61 non-obese subjects aged 20–65 years) that astaxanthin consumption (0, 6, 12, 18 mg/day for 12 weeks) ameliorates TG and HDL-C in correlation with increased adiponectin in humans. In this study, before and after tests, body mass index (BMI) and LDL-C were unaffected at all doses, however, TG decreased, while HDL-C increased significantly. Multiple comparison tests showed that 12 and 18 mg/day doses significantly reduced TG, and 6 and 12 mg doses significantly increased HDL-C. Serum adiponectin was increased by astaxanthin (12 and 18 mg/day), and changes of adiponectin correlated positively with HDL-C changes independent of age and BMI. Iwamoto *et al.* [26] demonstrated a significant inhibition of LDL-C oxidation in 24 healthy volunteers who took doses  of astaxanthin (1.8, 3.6, 14.4 and 21.6 mg/day for 2 weeks). Even Karppi *et al.* [30] in a 12-week randomized double-blind study involving 40 healthy non-smoking Finnish males assessed a significant plasma reduction levels of 12- and 15-hydroxy fatty acids in those taking astaxanthin (8 mg/day) suggesting an important reduced fatty acid oxidation due to astaxanthin. 
