Chronic-degenerative diseases are a growingly health problem all over the world 1. In Mexico, coronary heart disease and diabetes mellitus are the first and second leading causes of death between general population according to Statistics, Geography and Informatics' National Institute (INEGI) 2. This has been related with recognized environmental factors as a high caloric diet intake, leak of exercise, tobacco and alcohol consumption and genetic predisposition 34567. It is well known that the modification on lipid concentration is a useful approach to decrease cardiovascular mortality through prevention on development of atherosclerotic disease 8910111213.

Spirulina maxima, a filamentous and unicellular alga is a cyanobacterium belonging to the Oscillatoraceae family that usually grows in the alkaline waters of Africa, Asia, North and South America 14. Spirulina has been used as food additive because of its high content of proteins as well as essential nutrients like carotenoids, vitamins and minerals 151617. In addition, previous studies have demonstrated its several biological activities such as inhibit viral replication 151819, prevent anemia 20, decrease genotoxicity induced by drugs 21, prevent fatty liver disease 22232425 and has hypoglycemic 26 and hypolipemic properties 27282930. It has also been studied its effects on vasomotor responses on aortic rings proposing its antihypertensive activities in experimental models 313233. At this point, only few studies have evaluated these effects on human population.

The purpose of this study was to evaluate the effects of Spirulina maxima, orally administered, on serum lipids and blood pressure in a Mexican population after six weeks of treatment, as a possible alternative treatment for dyslipidemia and hypertension.

No changes were observed on AST and glucose values throughout the experimental period (35 ± 18 UI/L and 85 ± 13 mg/dL respectively, results not shown). On the other hand, as shown in Table 1, the initial concentration of lipids did not differ significantly between male (n = 16) and female (n = 20), suggesting their possible association as a single group. Because of the initial triacylglycerol concentrations were 254 ± 173 and 217 ± 184 mg/dL, for male and female groups, respectively, the values suggest a hypertriacylglycerolemic tendency in the studied sample. The other lipid values were in the optimal or limit ranges. In addition, both initial systolic and diastolic blood pressures did not differ significantly between male and female.

At the end of the experimental period there were significant differences in blood lipids after the Spirulina treatment (Table 2). Plasma TAG and TC concentrations were the most diminished (p = 0.001, Mann-Whitney and Student's-t tests) but LDL-C concentrations were also decreased (p = 0.01, Student's-t test), and HDL-C values were increased (p = 0.01, paired Mann-Whitney test). However, the univariate analysis showed that the changes on HDL-C and TC concentrations were dependent on TAG concentration (p = 0.247 and p = 0.108, respectively); while LDL-C concentration was independent of TAG values (p = 0.044). As mentioned before, there were no differences between initial and final AST or glucose concentration. Respect on blood pressure (Table 2) it was shown a significant difference between initial and final systolic and diastolic blood pressure records (p < 0.001 SYST-P; p < 0.05 DIAST-P, Tukey's comparison test). Furthermore, a significant decrease on systolic blood pressure was observed since the fourth week of Spirulina consumption (initial SYST-P 121 ± 9 vs. fourth week SYST-P 114 ± 10 mmHg, p < 0.05; vs. fifth week SYST-P 112 ± 8 mmHg, p < 0.01).

Previous studies have demonstrated the hypolipemic activity of Spirulina maxima in rats with and without toxic substances 27282930. Using a single intraperitoneal dose of 2 mL/kg carbon tetrachloride (CCl₄) as an hepatotoxic in order to induce non alcoholic steatohepatitis, it was demostrated that 5% Spirulina maxima in diet decrease serum AST, liver TAG and TC in rats. The same pattern was observed in the liver free fatty acids (with an important decrease on unsaturated fatty acids) and thiobarbituric acid reactive substances 24. These results suggest that Spirulina has hepatoprotective properties through decreasing on liver lipid profile and lipoperoxidation products. At this way, it has been demonstrated that Spirulina maxima prevents the development of fatty liver induced by simvastatin, ethanol and hypercholesterolemic diet in mice 29.

As previously mentionated, the purpose of this study was to evaluate the effects of Spirulina on human lipid metabolism and blood pressure levels. Parikh P et al., studied the effect of Spirulina supplementation at 2 g/day doses for two months on blood glucose levels, glycosylated hemoglobin and lipid profile of twenty-five diabetic type 2 subjects 26. They found a lowering of fasting and postprandial blood glucose levels and in the HbA1c level; this findings contrast with our results, where glucose levels kept stable during all studied period. Respect on lipid profile, the same report demonstrates a reduction on TAG, TC and in the atherogenic indices TC/HDL-C and LDL-C/HDL-C. Samuels R et al., also observed these effects in patients with hyperlipidemic nephrotic syndrome after supplementation with 1 g/day in the same period 34.

In our study, TAG, TC and LDL-C showed a significant reduction with an increase on HDL-C concentration after a study period of six weeks. However, changes on TC and HDL-C were dependent in TAG concentration, meanwhile LDL-C values decreased after treatment in an independent way. Before treatment, a high prevalence of hypercholesterolemia (27.8%, > 200 mg/dL), hypertriacylglycerolemia (41.7%) and hypoalphalipoproteinemia (27.7%) was found; this observation contrast with a Mexican nationwide previous study where hypertriacylglycerolemia was the second most common dyslipidemia (24.3%) after hypoalphalipoproteinemia (46.2% for men and 28.7% for women) 35; however, the prevalence of hypercholesterolemia was similar to that reported in a more recent study (26.5%) 36. At this point, after treatment it was observed a significant decrease in all prevalence parameters studied with a major effect observed in the oldest age group (49–65 years). This is very important because a lot of chronic-degenerative disorders related with dyslipidemia, incrementing their prevalence in this age group 1133738, could be attenuated with Spirulina consumption.

With regard to blood pressure, only 11% of studied population had normal levels before treatment, whereas 44% prehypertension, 31% hypertension stage 1 and 14% a stage 2. The hypertension prevalence on Mexican people has shown a clear increasing trend, 13.4% on 2000 survey to 22.7% on 2006 survey, indicating that the present prevalence (45%) could not represent the nationwide values 36. According the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) criteria 39, patients with prehypertension or hypertension in any stage, have to include in their treatment a balanced diet and exercise. Several natural products have been used to help in the treatment of hypertensive patients. Lima-Landman et al., in normal and hypertensive rats demonstrated that an aqueous extract of dried leaves from Cecropia glaziovii Sneth had an antihypertensive effect 40. Ojewole J et al., showed that Persea americana Mill aqueous leaf extract (25–800 mg/mL) caused bradycardia, vasorelaxation and hypotension in mammalian experimental models in response to a possibly increased synthesis and release of nitiric oxide 41. After supplementation with Spirulina it was observed 14% hypertension prevalence, 36% patients reached a normal blood pressure whereas patients with hypertension stage 1 or 2 decreased their levels to prehypertension (50%). These changes were observed in men and women, and that youngest group was more blood pressure responsive to Spirulina than the other age groups (data not shown).

The action mechanisms of Spirulina on lipid metabolism and blood pressure are not well understood yet. Nagakoa S et al., found that a concentrate of Spirulina platensis inhibited jejunal cholesterol absorption and ileal bile acid reabsorption, proposing that C-phycocyanin it's the molecule responsible for this effect 42. Li-Kun H et al., isolated an active component designed as glycolipid H-b2 and they found that this glycolipid inhibits pancreatic lipase activity in a dose-dependent manner, lowering rat plasma TAG levels 43. Furthermore, they found that phycocyanin inhibits pancreatic lipase at the same way. These effects could explain the hypocholesterolemic and hypotriacylglycerolemic effects seen on Spirulina maxima, treated patients, but no studies have been conduced at the moment.

On other hand, a diet supplemented with Spirulina maxima has showed to prevent synthesis and release of vasoconstricting metabolites of arachidonic acid induced by fructose and attenuates tension development in response to phenylephrine 33. Other reports, using an ethanolic extract, demonstrated an increased nitric oxide endothelium synthesis/release, a well known vasodilatation metabolite 31. At this point, it's well known that blood pressure could be increased in patients that develop vasoconstriction in response to certain metabolites or due to atherosclerotic process 44. Hypotension observed on patients could be explained on these effects. Hsiao G et al., have proposed that C-phycocyanin inhibits platelet aggregation through inhibition of calcium mobilization and mediation of free radicals released by platelet 45. These could be supported by a well recognized effect of Spirulina mediating several steps on inflammation process that finally reduces atherotrombotic plaque formation. Guan Y et al., have also proposed that high potassium, and low sodium contents of Spirulina, have positive effects on blood pressure 46. We found that supplementation with Spìrulina decreases LDL-C and increases HDL-C with a probably beneficial effect on atherotrombotic indices. Finally, our results also supported vasodilatation theory, as seen in a major effect of Spirulina in diastolic blood pressure mainly determinated by peripherical vessel resistance.

Actually, statins are recognized as the first-line therapy for cholesterol lowering. In a study conduced by Berne in type 2 diabetic patients, prescription of rosuvastatin (10 mg/day) by 4 weeks decreased significatively LDL-C levels in a mean percentage of 47.6%, TC in 33.6%, TAG in 19.2% and increased HDL-C in 4.4%, and demonstrated more response on lipid profile in comparison with atorvastatin at the same dose 47. Rangineni V et al., using dried Eclipta alba leaf powder (3 g/day) in mild hypertensive subjects, observed a reduction on LDL-C, TC and TAG with mean percentages of 24%, 17% and 14%, respectively 48. As mentionated before, treatment with Spirulina maxima, decreased significatively LDL-C, TC and TAG in a mean percentage of 17%, 8% and 20%, respectively, and increased HDL-C in 27%. These results support that Spirulina maxima could be used as an effective supplement on hypertriacilglycerolemic patients.

Respect of blood pressure, dried extract of Hibiscus sabdariffa, a widely used herbal medicinal product administrated for 4 weeks, decreased systolic and diastolic blood pressure in 11.58% and 12.21%, respectively 49. At this way, Eclipta alba dried leaf powder reduced mean arterial pressure by 15% 48. After treatment with Spirulina maxima, systolic and diastolic blood pressure decreased in a mean percentage of 8% and 6%, these results suggest that Spirulina maxima could be used as a supplement on blood pressure lowering therapy; however, these findings deserve more research in view that our study was performed in an open sample, non-representative and small population.

Finally, security on the use of Spirulina was demonstrated with no AST levels elevation trough evaluation period. There were no reports of adverse effects on population studied. Only idiosyncratic adaptative effects as: headache, flatulence, metheorism and increase of intestinal transit (not diarrhea) were reported on the first week of treatment. This is according with other reports where security of oral administration was studied 505152.

The present results demonstrate that Spirulina maxima has hypolipemic effects, especially on the TAG concentration and the LDL-C but indirectly on TC and HDL-C values and positive effects on lowering blood pressure. We propose that because of these pharmacological properties, Spirulina could be used as a dietary supplement on dyslipidemic and hypertensive patients.

The author(s) declare that they have no competing interests.

PVTD participated in the collection, design, analysis and interpretation of data and writing of the manuscript; AFH participated in the collection and analysis of data and performed the statistical analysis and writing of the manuscript; MAJO participated in the design, analysis and interpretation of data and writing of the manuscript. All authors read and approved the final manuscript.