Supplementing spirulina for metabolic maladies

Metabolic syndrome^[1] is a cluster of conditions that appear to revolve around insulin resistance. This cluster of conditions, depicted in Figure 1, includes impaired glucose tolerance (post-meal blood sugar), elevated triglycerides, and aberrant cholesterol. Metabolic syndrome is a risk factor for type 2 diabetes^[2] (T2DM), cardiovascular disease^[3] (CVD), and other chronic diseases, including non-alcoholic fatty liver disease (NAFLD). As of 2012, the prevalence of metabolic syndrome in the U.S. was about 35% in adults^[4] and about 5-7% in young adults^[5]. As such, treatments that can address metabolic syndrome are needed.

Lifestyle and pharmaceutical interventions are the leading approaches to addressing and managing metabolic syndrome. In terms of lifestyle modification^[6], exercise, caloric restriction, and weight loss are all efficacious in the management of the syndrome. Pharmaceutical interventions involve targeting metabolic syndrome components. These include, for example, the use of glucose-lowering agents like metformin and/or lipid lowering agents such as statins, fenofibrates, or thiazolidinediones.

In addition to lifestyle and pharmaceutical interventions, there have been efforts to discover and implement nutraceutical interventions like fish oil, vitamin D, and omega-3 fatty acids. Spirulina, a species of cyanobacterium^[7] (blue-green algae), has been used as a food supplement due to its high nutrient content, as it contains calcium, magnesium, vitamin E, and vitamin B₆. Recently, however, some evidence has suggested that spirulina might exert beneficial effects on metabolic syndrome. For example, a study^[8] found that among people with type 2 diabetes, spirulina led to improvements in serum triglycerides, independent of changes in bodyweight. The present study is a systematic review and meta-analysis of RCTs regarding the effect of spirulina on glucose and lipid metabolism among participants with metabolic syndrome.

Metabolic syndrome is a cluster of conditions that likely reflect insulin resistance, such as elevated blood glucose and blood lipids. Spirulina is a blue-green algae that displays some glucose-lowering and lipid-lowering effects. The present study is a systematic review and meta-analysis on the effect of spirulina on glucose and lipid metabolism among people with metabolic syndrome.

The study under review was a systematic review and meta-analysis of randomized controlled trials with either parallel or cross-over designs examining the effects of spirulina on glycemic control and serum lipoproteins. The study was not preregistered and did not follow PRISMA guidelines. Furthermore, it was not explicitly stated whether metabolic syndrome was an inclusion criterion.

Outcomes of interest were glycemic control (fasting plasma glucose, fasting insulin, HOMA-IR, QUICKI, HbA1c, and HOMA-IR) and blood lipids (total cholesterol, LDL-C, HDL-C, and triglycerides). Primary outcomes were not specified.

Weighted mean difference (WMD) between the spirulina and control group was used for pooling data to determine effect sizes. Subgroup analyses were also performed based on sample size, dosages, and duration of the study.

The researchers stated that they assessed study quality using the Cochrane Collaboration’s risk of bias tool^[9], and publication bias using Begg’s and Egger’s regression tests, but they were not reported in the paper. Heterogeneity was evaluated using Cochrane’s Q test and I-squared test.

A total of 14 studies, with 510 total participants, were ultimately included in the meta-analysis. Studies were done in India, Korea, Iran, Poland, and Romania and used 0.8 to 14 grams of spirulina.

This meta-analysis of 14 studies examined the effects of spirulina on glycemic control and blood lipids in people with type 2 diabetes and other metabolic diseases. Studies used 0.8 to 14 grams of spirulina for six to 16 weeks.

There was no effect of spirulina on HbA1c, triglyceride levels, or LDL-C/HDL-C ratio. Supplementation with spirulina led to a significant reduction in fasting insulin (WMD = -0.53), total cholesterol (WMD = -20.50), LDL-C (WMD = -19.02), and VDL-C (WMD = -6.72), while it led to a significant increase in HDL-C (WMD = 1.42). For more on weighted mean differences, check out the sidebar in Study Deep Dives #17, “Is organic meat healthier?”. There was no explicit reporting of HOMA-IR or QUICKI. The dosing did not have a substantial impact, with doses of less than four grams or more than four grams per day having similar effects for most outcomes, with some exceptions (HbA1c and LDL-C/HDL-C ratio). The length of the study did not have a consistent effect on the outcomes either, except for HbA1c, in which studies longer than 12 weeks found lower HbA1c, while studies shorter than 12 weeks did not. Check out the full details of the subgroup analyses in Figure 2.

Heterogeneity was moderate to high, ranging from I₂=34% to I₂=98%, with all but one outcome showing an I₂>60%. This indicates that the findings of different studies were quite variable. Publication bias and the results of the Cochrane risk of bias tool were not reported.

Supplementation with spirulina improved fasting insulin and serum lipids but did not have an impact on HbA1c or triglycerides. Spirulina dose and study duration didn’t consistently modify the outcomes.

The current systematic review and meta-analysis shows supplementation with spirulina improves some aspects of glycemic control and lipid metabolism that are commonly disturbed in metabolic syndrome. These data indicate that spirulina may be an effective, non-pharmacological therapy for improving key features of metabolic syndrome.

The present data suggest that spirulina may help reduce the overall burden of disease that is associated with metabolic syndrome. For example, metabolic syndrome increases the risk of cardiovascular disease^[10] and diabetes^[11]. The present study shows that spirulina reduces key features of metabolic syndrome, namely dyslipidemia and elevated fasting insulin (a marker of insulin function), that link to cardiovascular disease and diabetes.

There are several limitations of the current study. First, there were a relatively small amount of studies for each of the outcomes, with many limited to five studies or fewer. Second, outcomes were highly variable between studies, and within the limits of the subgroup analysis that was not well explained by obvious differences in study design, like spirulina dose and study duration. Third, the results of the examination of bias by the Cochrane bias tool and Begg’s and Egger’s tests were not reported, so there is limited insight into if or how the results might be biased. Finally, the authors did not report units for the measurements reported in the results, so it is difficult to determine a true magnitude of the effects.

For people with aspects of metabolic syndrome, supplementation with spirulina improves some aspects of glucose and lipid metabolism. This improvement would be expected to reduce the risk of other diseases linked to metabolic syndrome, including cardiovascular disease and diabetes. However, the study reported very high levels of heterogeneity and no results for systematic biases were reported.

Metabolic syndrome has increased dramatically in prevalence over the last half century and it is estimated that roughly one-third^[12] of all adults in the U.S. have metabolic syndrome. This places a substantial disease burden on the population and interventions that target metabolic syndrome are needed.

The present study provides evidence that spirulina may be a viable strategy for improving key features of metabolic syndrome, primarily blood glucose and blood lipids. While this meta-analysis did show varied results depending on the outcome, there was a consistent signal showing benefit on several metabolic parameters.

Spirulina may be an effective adjuvant treatment in addition to current standard of care interventions due it its mechanisms of action. For example, oxidative stress^[13] is considered to be one of the key contributors to insulin resistance. Spirulina has shown anti-oxidant properties in animal models of diabetes. For example, spirulina was shown to reduce measures of oxidative stress and increase NAD(P)H oxidase^[14] (an endogenous antioxidant) in rodents with type 2 diabetes. Additionally, spirulina was shown to reduce expression of the inflammatory mediator tumor necrosis factor alpha^[15] in mice that were made hyperglycemic through high-dose fructose overfeeding. Putting this information together, as shown in Figure 3, implies that both anti-inflammatory and antioxidant mechanisms may be at play.

Spirulina shows promise for providing therapeutic benefit for people with metabolic syndrome. It appears to work primarily by providing antioxidant benefits through NAD(P)H oxidase and potentially reducing inflammation.

Q. Based on the findings of the study, it appears that the dose of spirulina doesn't matter, in terms of having an effect on some markers associated with metabolic syndrome. So, what is the minimal dose one needs to take to have an effect?

The dose response relationship is not well known at this time and the subgroup analysis by dose did not show any meaningful differences across outcomes in the present study. This makes it difficult to determine the true minimal effective dose. However, the present study did show that 800 milligrams was effective enough to see results. It is important to remain cautious about the lack of clarity on dosing and more work needs to be done to answer this question.

Q. If spirulina is a grown and harvested algae, how do I know it is safe?

Spirulina is considered a food grade product and generally undergoes rigorous testing^[16]. For example, it undergoes microbiological and chemical composition tests as well as tests for contaminants like heavy metals, pesticides, and extraneous materials. However, caution may still be warranted as there have been reports of spirulina leading to adverse outcomes, like rhabdomyolysis^[17].

Metabolic syndrome affects almost a third of the entire U.S. population, representing one of the most widespread health conditions in the nation. While pharmacological approaches are considered the standard of care, there are several non-pharmacological therapeutics that show promise as well.

Spirulina, a blue-green algae that is high in vitamins and bioactive compounds, has shown some promise in improving hallmark features of metabolic syndrome. Previously, randomized controlled trials have yielded mixed results, motivating this systematic review and meta-analysis. This study found that spirulina improved some aspects of glycemic control and serum lipids in people with metabolic syndrome. However, given many of the limitations of this paper, it is difficult to draw any real conclusions about the clinical utility and/or significance of the algae.

The present study does have some limitations that impact the ability to draw robust conclusions, including limited sample size, high heterogeneity, and no reporting of systematic biases present in the literature.