Cholesterol is the building block for cell membrane and a precursor of steroid hormones. It forms several distinct particles with lipoproteins, mainly high density lipoproteins (HDL), low density lipoproteins (LDL) and very low density lipoproteins (VLDL). It is well established that LDL and VLDL cholesterol levels are atherogenic whereas HDL-cholesterol has protective effects on the development of atherosclerosis [11,12]. Increased LDL and VLDL levels are the major independent risk factor for cardiovascular events whereas low level of HDL and elevated triglycerides (TG) are also recognized as residual risk for cardiovascular diseases . Agents with the ability to decrease LDL/VLDL or total cholesterol levels, increase HDL cholesterol or lower TG have beneficial effects on preventing cardiovascular diseases.
The hypolipidemic effect of Spirulina or its extracts have been demonstrated in various animal models including mouse, rat, hamster and rabbit. The cholesterol lowering activity of Spirulina was first reported in albino rats , followed by in mice . In the mouse study, supplementation of 16% Spirulina in a high fat and cholesterol diet resulted in a significant reduction in total serum cholesterol, LDL, VLDL cholesterol and phospholipids whereas serum HDL cholesterol was concurrently increased. In addition, high hepatic lipids induced by the high fat and cholesterol diet were markedly reduced by Spirulina consumption .
Since the initial report of hypolipidemic effects of Spirulina, several in vivo studies were carried out in rats and mice under various experimentally induced conditions. In one study , hyperlipidemia was induced in Wistar rats by a high fructose (68%) diet. Inclusion of increasing percentages of Spirulina (5, 10, and 15%) in the diet significantly improved the hyperlipidemic profiles. Correlating with such improvement in lipid profiles, Spirulina feeding resulted in a significant increase in lipoprotein lipase and hepatic triglyceride lipase activity. Such increased lipase activity by Spirulina was suggested as a mechanism for improving the hyperlipidemia induced by high fructose diet. In another study with rats , fatty liver was induced by intraperitoneal injection of carbon tetrachloride (CCl4), resulting in an increase in liver total cholesterol and triacylglycerols. However, such increases were significantly reduced by feeding oil extracts of Spirulina or defatted fraction of Spirulina. In addition, CCl4-induced increase in total cholesterol level was completely prevented by feeding a diet containing whole Spirulina. A similar study was performed in CD-1 mice . Fatty liver was induced by a daily dose of simmvastatin (75 mg/kg body weight) for five days with a high cholesterol diet and 20 percent ethanol in the drinking water. Serum and hepatic triacylglycerols, total lipids and cholesterol were all significantly increased. However, Spirulina feeding for two weeks prior to the onset of fatty liver induction decreased hepatic total lipids by 40%, triacylglycerols by 50% and serum triacylglycerols by 45%, accompanied by a 45% increase in serum HDL cholesterol. The hypolipidemic activity of Spirulina was also confirmed in a diabetic mouse model . Diabetic condition was induced by administration of alloxan (250mg/kg body weight), resulting in evident fatty liver accompanied by altered serum and hepatic triacylglycerols and cholesterol levels. However, mice receiving a diet containing 5% Spirulina one week after the administration of alloxan for four weeks totally prevented fatty liver production, decreased serum and hepatic triacylglycerols, and fully or partially normalized HDL, LDL and VLDL cholesterol levels. The study also showed that female mice were more resistant to diabetes induction by alloxan whereas more responsive to Spirulina treatment than male mice.
The hypolipidemic effects of Spirulina observed in mice and rats were verified in two recent studies with hamsters  and rabbits . A group of hamsters fed an atherogenic diet supplemented with Spirulina or its ingredient phycocyanin exhibited lower total cholesterol, LDL and VLDL cholesterol whereas HDL cholesterol was not affected. Furthermore, aortic fatty streak area was significantly reduced in hamsters receiving Spirulina supplement, indicating the antiatherogenic activity of Spirulina . In the study with rabbits, hypercholesterolemia was induced by a high cholesterol diet and the effects of feeding Spirulina (0.5 g daily) for 30 and 60 days on the induced hypercholesterolemia was evaluated . At the end of the study, serum total cholesterol was decreased by 49% while HDL cholesterol was increased by 25%. No significant changes in serum triacylglycerols were observed.
Taken together, the results from studies with various animal models consistently demonstrate the hypolipidemic activity of Spirulina, lowering serum total cholesterol, LDL and VLDL fractions. In addition, other improvements in lipid profile were also observed in certain studies, including an increase in HDL cholesterol levels, decrease in atherogenic indices and triacylglycerol levels.
A number of human clinical trials have been performed to evaluate the hypolipidemic activity of Spirulina (Table 1). The target populations include healthy volunteers, patients with ischaemic heart disease, type 2 diabetes and nephrotic syndrome, and elderly subjects with or without hypercholesterolemic condition.
The first human study was carried out in 1988 with 30 healthy male volunteers with mild hyperlipidemia or hypertention . The 30 subjects were divided into two groups; one group received 4.2g of Spirulina daily for 8 weeks whereas the other group was given Spirulina for 4 weeks, followed by on regular food for another 4 weeks. Intake of Spirulina for 4 or 8 weeks significantly decreased total serum cholesterol and the decrease was more marked in mild hypercholesterolemic than in normocholesterolemic subjects. Discontinuation of Spirulina supplement for 4 weeks resulted in returning of the cholesterol level to the baseline (prior to Spirulina supplementation) and HDL levels were slightly increased but not statistically significant. There were no changes in serum triglycerides and body weight. In addition, no subjects reported adverse effects during the study. In a recent before-and-after clinical trial with 36 healthy volunteers (16 male and 20 female) between ages 18 to 65 , ingestion of Spirulina at a dose of 4.5g daily for 6 weeks decreased total plasma cholesterol and triacylglycerols by 10% and 28 %, respectively. Lipoprotein analysis showed that HDL cholesterol was increased by 15% whereas LDL cholesterol was significantly decreased. In addition, both systolic and diastolic blood pressures were significantly reduced in both men and women.
The hypolipidemic effect of Spirulina was also demonstrated in ischaemic heart disease patients with hypercholesterolemic condition (serum total cholesterol levels above 250mg/dL) , a total of 30 patients were divided into three groups. Two treatment groups received 2 or 4g of Spirulina daily for three months whereas control group was not supplemented with Spirulina. At the end of the supplementation, plasma total cholesterol was significantly decreased by 22.4% and 33.5% in groups receiving 2g and 4g Spirulina, respectively, whereas no significant change was detected in the control group. Lipoprotein fraction analysis showed that LDL and VLDL cholesterol levels were significantly reduced by 31% and 45%, and 22% and 23% in the two treatment groups, respectively. On the other hand, HDL was significantly increased by 11.5% and 12.8%. Furthermore, the concentration of triglycerides was significantly reduced by 22% and 23%. Finally, a significant loss in body weight was observed in both treated groups whereas no change was detected in the control group. Thus, it was concluded that supplementation of Spirulina at a daily dose of 2 or 4 g for three months significantly improved the lipid profile of the patients with ischaemic heart disease.
Non-insulin-dependent diabetes mellitus (NIDDM) or type 2 diabetes mellitus is a recognized independent risk factor for cardiovascular diseases, such as coronary artery disease. The distinction between type 2 diabetes mellitus and cardiovascular disease has been blurred and prevention of cardiovascular diseases is becoming an integrated part of diabetes management. Patients with type 2 diabetes are frequently affected by atherosclerotic vascular disease. The abnormalities of both quantity and quality of lipoproteins in type 2 diabetes patients contribute to an increase in atherosclerotic vascular disease. So far, four human clinical studies have been performed to investigate the hypolipidemic and hyperglycerolemic effects of Spirulina in type 2 diabetic patients [25–28]. The two early studies were carried out by Dr. Iyer’s group in India [25,26]. In a before-and-after study with 15 type 2 diabetes patients , supplementation of Spirulina at a dose of 2g daily for 2 months resulted in a significant decrease in total serum cholesterol, triglycerides and free fatty acid levels. Analysis of lipoprotein fractions revealed that LDL and VLDL cholesterol levels were appreciably reduced. Blood sugar and glycated serum protein levels were also significantly decreased. In a second randomized and controlled study , twenty-five patients with type 2 diabetes mellitus were randomly assigned to a study or control group. Subjects in the study group received Spirulina at a dose of 2g/day for 2 months. At the end of the study, total serum cholesterol and LDL fraction were reduced whereas HDL was slightly increased in the study group. As a result, a significant decrease in atherogenic indices and the ratios of total cholesterol/HDL and LDL/HDL was achieved. Triglycerides and fasting and post prandial blood glucose levels were significantly reduced. Finally, the level of apolipoprotein B showed a significant fall with a concurrent significant increase in the level of apolipoprotein A1. Thus, the hypolipidemic and hypoglycerolemic effects of Spirulina were consistently detected in both clinical studies with type 2 diabetic patients.
The findings from the early studies were confirmed in the two recent human clinical trials with type 2 diabetic patients [27,28]. Both trials were randomized, controlled studies with a relatively large sample size. One study enrolled 37 patients being randomly divided into a treatment or control group . Intake of Spirulina at a dose of 8g daily for 12 weeks significantly reduced total serum cholesterol, LDL fraction and triglyceride levels. Subjects with higher initial total cholesterol, LDL-cholesterol and triglyceride levels showed higher reduction. In addition, blood pressures were also decreased. The second trial included 60 male patients aging from 40 to 60 years . The subjects were randomly assigned into two treatment groups or a control group. The two treatment groups received 1 or 2g Spirulina daily for two months. A significant decrease was observed in serum total cholesterol, triglycerides, LDL and VLDL cholesterol in the two treatment groups. Both fasting and post prandial blood glucose levels were also decreased by 16.3% and 12.5% in 1g-treated group and by 21.8% and 18.9% in 2g-treated group whereas no significant changes were detected in the control group. It was also found that mean carbohydrate and protein intake was significantly decreased in both treatment groups. Taken together, the data are consistent with the notion that Spirulina is a promising agent as a functional food supplement for controlling hyperglycerolemia and hypercholesterolemia and thus reducing cardiovascular risk in the management of type 2 diabetes.
The hypolipidemic benefit of Spirulina was also reported in patients with nephrotic syndrome and hyperlipidemia . One group of patients received medication alone whereas the other group received medication and Spirulina capsules. Supplementation of Spirulina at a dose of 1g daily for 2 months resulted in a reduction in total serum cholesterol, LDL fraction and triglycerides by 46mg/dL, 33mg/dL and 45mg/dL, respectively. The ratios of LDL/HDL and total cholesterol/HDL were also decreased significantly. It was thus concluded that Spirulina supplementation was an effective approach to reduce the increased levels of lipids in patients with hyperlipidemic nephrotic syndrome.
Total and LDL cholesterol levels increase with aging [30,31] as does the incidence of cardiovascular disease . Three human clinical studies have been carried out to investigate the therapeutic effects of Spirulina in elderly population [33–35]. In one study with 12 subjects (6 male and 6 female) between the ages 60 and 75 , subjects received a supplement of Spirulina at a dose of 7.5g/day for 24 weeks. Plasma concentrations of triglycerides, total cholesterol and LDL fraction were decreased after 4 weeks of the supplementation while no changes were observed in dietary intake and anthropometric parameters. It was also noticed that no differences in the hypolipidemic effects of Spirulina were observed between mild hypercholesterolemic (cholesterol at or above 200mg/dL) and normocholesterolemic subjects (cholesterol below 200mg/dL). The second before-and-after trial included 26 elderly women aged over 60 with hypercholesterolaemic condition (serum total cholesterol above 200mg/dL) . Intake of Spirulina at a dose of 7.5mg/day for 8 weeks resulted in a significant reduction in serum levels of total cholesterol, LDL cholesterol and oxidized LDL. In addition, apolipoprotein B levels were also decreased. The most recent clinical trial was a randomized, double-blinded, and placebo-controlled study . Seventy eight subjects between the ages 60 and 87 were randomly assigned into a study or placebo group. After consumption of Spirulina at a dose of 8g/day for 16 weeks, total plasma cholesterol and LDL fraction were significantly reduced in female subjects whereas the lowering effect on plasma total cholesterol and LDL fraction was not statistically significant in male subjects. The levels of HDL fraction and triglycerides did not change after the intervention in both men and women. The data from those clinical trials largely support the notion that Spirulina supplement is beneficial for managing aging-induced alterations in lipid profile in the elderly population.
Taken together, although differences in study design, sample size and patient conditions resulting in minor inconsistency in response to Spirulina supplementation, the cumulative data from those studies clearly demonstrate the hypolipidemic activity of Spirulina in human. However, the majority of those human clinical trials are suffered with limited sample size and poor experimental design. Additional clinical trials with large sample size and high quality experimental design are warranted to confirm the hypolipidemic and hypoglycerolemic benefits of Spirulina in various target populations.