To the best of our knowledge, the present study is the first evidence offered to support the hypothesis that the regular consumptions of Chlorella supplement (5 g/day) over 4 weeks significantly reduced serum TG, TC, non-HDL-C, VLDL-C, HDL-C/TG, and apo B in subjects with mild hypercholesterolemia using RCT study design. This study also demonstrated that daily consumption of Chlorella supplement resulted in significant increases inserum lutein/zeaxanthin and α-carotene concentrations. In addition, the changes of serum TG and TC appeared to be associated with the changes in serum lutein/zeaxanthin and α-carotene.
Some studies in open-label (“before and after”) design with relatively small numbers of subjects have shown the effect of Chlorella, focusing on the serum cholesterol levels rather than overall lipid and carotenoid profiles. Okuda et al. showed that the daily intakes of 5 g of Chlorella for three months significantly lowered the TC of subjects with hypercholesterolemia (n = 16) to almost the normal level. In another study, Youko et al. demonstrated reductions in TC and LDL-C concentrations after 9 g of Chlorella supplementation for 12 months in patients with hyperlipidemia (n = 9). Sansawa et al. found that the daily ingestion of 3 g of Chlorella for three months lowered serum TC and LDL-C in patients with mild hypercholesterolemia (n = 20). These small studies suggested a potential of Chlorella supplementation for reductions of TC at doses of 3–9 g, providing a rationale for further evaluations of Chlorella in a randomized, placebo-controlled trials.
In the lipoprotein lipolytic cascade, apo B is required for the secretion of VLDL from the liver and converted to intermediate-density lipoprotein (IDL) by lipoprotein lipase in the endothelial surface of capillaries. The IDL particles can be rapidly taken up and then catabolized mainly in the liver via apo E, a high-affinity ligand for the receptor. However, some IDL particles escape hepatic uptake and remain in the circulation due to lack of apo E and are further converted to LDL . The binding affinity of apo B was relatively low, and thus, LDL particles circulated for a relatively prolonged period before binding to LDL receptors throughout the body [27, 28]. There is a systematically only one apo B per LDL particle and thus plasma level of apo B is strongly associated with LDL particle number, which is an important predictor of cardiovascular risks . Conversely, the HDL accepts cholesterol from peripheral cells and transports it to the liver for bile production. Apo A1 is the major protein constituent of HDL particles, mediating reverse cholesterol transport . It is important to note that the most pronounced effect of Chlorella in the current study were decreases in VLDL and apo B concentrations. This result implicates that there are slowed secretion of apo B and VLDL into the circulation or faster catabolism of VLDL in the liver. This is speculative but the first part is consistent with the previous findings that Chlorella plays an important role in inhibiting the intestinal absorptions of dietary lipids in animals [8–10]. In addition, lowering apo B compromises lowering LDL particle number and promotes CVD risk. It is also worth noting that, in the present study, four weeks of Chlorella supplementation produced no noticeable effects on HDL-C, apo E, and apo A1 compared with the control group, implicating that reverse cholesterol transport was unaffected by Chlorella consumption. The design of the current study did not allow the direct determination of cholesterol absorption. Considering all the results together, however, we can assume that the inhibition of intestinal lipid absorption may have caused the serum lipid profile changes observed in the Chlorella group.
Chlorella provides a wide range of nutrients and phytochemicals that work synergistically to optimize lipid metabolism. It contains a relatively high percentage of omega-3 fatty acids , which are known not to inhibit chylomicron assembly in the intestine, but to inhibit VLDL assembly in the liver . Chlorella is a good source of dietary fiber that affects lymphatic cholesterol and triglyceride absorption by increasing gut viscosity, altering the composition of the bile acid pool, or producing fermentation products in the intestine . Chlorella is also a good source of carotenoids and it significantly increased serum concentration of lutein/zeaxanthin and α-carotene. The steps of carotenoid absorption are similar to those for dietary lipids: the release from the food matrix, solubilization in mixed micelles, packaging into chylomicrons, and secretion into the lymphatic system . Therefore, one can assume that the presence of increased concentrations of carotenoids released from Chlorella compete with dietary lipids for incorporation and transport in lipoproteins, therefore causing the decreased serum lipid levels. In a previous animal study Nicolle et al. investigated the effects of carrot supplementation on lipid metabolism in rats, suggesting that dietary carotenoid consumption modifies lipid absorptions. In this study, we found that individuals with higher levels of serum lutein/zeaxanthin and α-carotene had greater potentials to reduce serum TG concentrations, supporting the notion that carotenoids may inhibit TG absorption. However, contrary to TG, no or weak positive correlation was found between the changes in serum carotenoids and the changes in TC. One possible explanation for these conflict may be that the polar carotenoids are mostly distributed in association with cholesterol-rich lipoproteins in the serum , which masks the degree of inhibitory effects of carotenoids on cholesterol absorption. This notion is further supported by the results of Loane et al., who reported a positive association between serum lutein concentration and both serum LDL and HDL level among healthy subjects.
There are several limitations in this study. First, the suggested molecular mechanism by which Chlorella are thought to exert their effect was not directly determined. Despite this limitation, however, our findings raised the possibility that the effects of Chlorella on the inhibition of intestinal absorption of both dietary and endogenous lipids may have caused the serum lipid profile changes. Another limitation of this study is that there was no more biochemical data to show the localization of carotenoids in lipoproteins. Future studies are warranted to prove these initial findings.