Multiple risk factor syndrome or metabolic syndrome (i.e. the coexistence of several risk factors for artherosclerosis, including hyperglycemia, dyslipidemia and hypertension in the same individual) is a growing medical problem in industrialized countries 12, with obesity being the central and causal component.

Obesity, which is defined as an excess deposition of fat in body fat stores, is determined using the Body Mass Index or BMI scale. It could also be determined by bioelectrical impedance methods, which gives an estimate of the amount of fat stores in the body. The distribution of these fat stores (android or gynoid) is known to be an independent risk factor in obesity-related diseases.

In the United States, over 60% of the adult population is now overweight or obese 3 and 47 million people have metabolic syndrome, which will soon overtake cigarette smoking as the number one risk factor for heart disease 45. Obesity and its related complications were considered for a long time to be limited to industrialized developed countries. This is however no longer the case, with a high incidence now in developing countries who have undergone lifestyle changes which increase the incidence of these diseases.

Obesity has been shown to contribute to high serum cholesterol, low HDL cholesterol and hyperglycemia, all of which increase the chances of cardiovascular disease (CVD) 678. Correlations between central obesity and high blood pressure, high blood cholesterol, low levels of high density lipoprotein cholesterol and high fasting blood glucose levels have been shown for both sexes in various racial and ethnic groups 678910.

The complications of obesity are worsened by oxidative stress (imbalance between pro-oxidants and antioxidants in favor of pro-oxidants). Recent research has shown that long-term caloric restriction promotes longevity and chronic overeating and obesity results in a condition that mimics the aging process, which explains the higher prevalence of inflammation and free radicals, and metabolic and cardiovascular diseases in overweight individuals. Obesity may induce systemic oxidative stress, and increased oxidative stress in accumulated fat is one of the underlying causes of dysregulation of adipocytokines and development of metabolic syndrome 6.

The increased chance of CVD and type 2 diabetes requires therapeutic consideration for the vast numbers of overweight/obese persons now at high risk for these diseases 11. The current International Diabetes Foundation recommendations for preventing or delaying the development of diabetes include both primary and secondary interventions. The former emphasizes lifestyle changes such as calorie restriction and increased physical activity, and the latter (for people at high risk for CVD) uses pharmacological agents 12 that specifically target individual components of metabolic syndrome 121314151617. When used by obese patients in combination with dietary regimes or alone, these agents can produce some weight loss and some prevention or reversal of accompanying complications. The role of pharmacotherapy, however, has been compromised by safety issues leading to the withdrawal of some medications from the market 1819 or from advanced stages of clinical testing. Furthermore, agents that can address the underlying issues behind many of the complications associated with metabolic syndrome have yet to be developed.

This study investigated the effects of ProAlgaZyme algae infusion ("PAZ") vs. placebo on indicators of cardiovascular health by assessing markers of inflammation and oxidative stress, blood sugar, weight and blood lipids in overweight and obese people. ProAlgaZyme (PAZ) is a freshwater algae infusion that has been consumed as a liquid dietary supplement for over 3 decades. PAZ was first marketed as Lebenszeit^TM, meaning "Lifetime" in German, in the 1980's by Ponce de Leon Medical Development Corp. in the U.S., in reference to the legendary fountain of youth. The product became known as ProAlgaZyme or "PAZ" in 2003. The infusion is an aqueous fermentation product of a proprietary blend of freshwater organisms including green algae discovered over 30 years ago within a natural source, and has since been cultivated under controlled conditions. ProAlgaZyme oral liquid dietary supplement, the filtrate of the fermentation process, typically has less than 100 ppm total dissolved solids consisting of approximately 90% salts (free of heavy metals at a detection limit of <0.1 ppm) and a unique blend of organic constituents currently undergoing full characterization.

Anecdotal reports in the U.S. of improvements in symptoms of inflammatory and metabolic conditions after PAZ consumption led to our interest in evaluating PAZ's potential to positively affect factors associated with metabolic syndrome and cardiovascular health. Particularly relevant to this study were anecdotal reports of improvements in high sensitivity C-reactive protein, blood sugar metabolism and body weight, and increases in energy. Patients with metabolic syndrome were specially suited as subjects in this study, as this diagnosis includes both metabolic and inflammatory components. The human clinical study results are reported here.

ProAlgaZyme had a significant effect on the various parameters studied in metabolic syndrome patients over a 10 week period (Table 1). The raw data at 4, 8 and 10 weeks are in additional file 1: MetSyn_Data.xls.

A total of 52 overweight or obese participants aged 25 to 60 years completed the study (87%). Eight patients dropped out of the study; three gave as a reason difficulty in maintaining the dosing schedule, 3 others did not give any reason, while 2 of them moved out of town. While no side effects were reported in either the dropouts or in those completing the trial, it is possible that unreported reactions to the ProAlgaZyme treatment led to the decision in this subgroup to stop participation. Mitigating against this possibility are results from a separate trial (submitted for publication), in which 20 HIV+ individuals received 20 ounces per day (5 times the dose used in this study) for a 12-week period, with no side effects observed or reported.

In this study, we evaluated the effects of ProAlgaZyme algae infusion (PAZ) on indicators of metabolic syndrome and subsequent risk factors for cardiovascular disease. The results obtained showed that PAZ is efficient in improving multiple markers of metabolic syndrome including weight, blood lipids, fasting blood glucose and markers of inflammation, and may have a significant effect on cardiovascular health. The infusion is effective in reducing body weight in obese patients, with an average weight loss of 4.2 kg (9 lbs.) over 10 weeks. This reduction seems to be caused by the decrease in percentage of body fat observed throughout the study in the PAZ group, with an average loss of 2.6% body fat. Accumulation of body fat is tightly linked to non-insulin dependent diabetes mellitus (NIDDM). In this study, results also showed a hypoglycemic effect of PAZ, with an average reduction in fasting blood glucose of nearly 19% or 18.50 mg/dL. It would be interesting to investigate whether this effect could also be observed in people living with diabetes mellitus. Several hypotheses can be made in order to explain the mechanism of the weight/fat loss and blood glucose lowering effect. It should be noted that changes in blood insulin were not significant. It is possible that PAZ may contain some molecule(s) able to act on basal metabolic rate (BMR), thus increasing energy expenditure and leading to consumption of excess fat stores. This hypothesis could be assessed in a further study using calorimetry. Appetite reducers in some cases could be linked to reduced energy intake; however, it is unlikely to be the case with the use of PAZ, since most participants reported an increased rather than reduced appetite. The reduction in inflammation induced by PAZ, as evidenced by strongly decreased levels of C-reactive protein (mean change -6.20 mg/L; -57%), should be considered here, as it may be responsible for improving blood sugar profiles through a reversal of the autoimmune component of insulin resistance. With regard to lipid profile, strong hypolipidemic effects of PAZ in the test group over a 10-week period suggest its potential protection against cardiovascular diseases through a reduction in total cholesterol (mean -64.8 mg/dL; -32%), LDL-cholesterol (mean -40.6 mg/dL; -30%) and triglycerides (mean -18.8 mg/dL; -11%), and an increase in HDL-cholesterol (mean 15.4 mg/dL; +42%). 1 out of 2 test subjects (n = 11) observed an increase of ≥15 mg/dL in HDL-cholesterol over 10 weeks, and nearly a third (n = 7) saw an increase of 20 mg/dL or more. All subjects taking ProAlgaZyme (vs. only 11% of subjects on placebo) saw an increase of ≥1 mg/dL in HDL-C. An increase in HDL-cholesterol alone has been shown to impart possible health benefits in overweight and obese people and reduce the risk for cardiovascular disease 2021. This increase in HDL-C coupled with a decrease in the concentrations of LDL-C and triglycerides could lead to a lowering of atherogenicity and therefore a significant reduction in the potential incidence of coronary heart disease 22. Ten weeks of treatment with ProAlgaZyme brought about a mean reduction in total cholesterol of over 60 mg/dL, while only a 23.2 mg/dL (0.6 mmol/L) reduction of serum cholesterol has been shown to correlate with a 54% reduction of risk 23. Additionally, half of test subjects observed a decrease in LDL-C of at least 36 mg/dL. PAZ may achieve these effects through interaction with enzymes involved in cholesterol biosynthesis, by catalysis of LDL-cholesterol conversion into bile salts, or by other mechanisms. Since a recruitment criterion in the study was hyperlipidemia, these results show clearly that PAZ could be used successfully for the relief of dyslipidemia. This improvement in lipid profile, coupled with a decrease in inflammatory markers, could also assure a protection against lipid plaque buildup and rupture in artery walls, and therefore against cardiovascular disease and hypertension, as suggested in the study by a decrease in blood pressures in PAZ patients. Yet, we cannot exclude the presence of hypotensive molecules in the infusion. Reductions in C-reactive protein, RBC sedimentation rate and Interleukin-6 (IL-6) were significantly greater in the PAZ group compared to placebo, suggesting that PAZ also has a preventive effect on the pro-inflammatory state generally linked to metabolic syndrome, and may be useful for the treatment of other inflammatory disorders. 100% of test subjects (n = 22) observed a 20% or more reduction in CRP (≥2.0 mg/L), and half of these (n = 11) experienced a reduction of 55% or more (≥6.0 mg/L). Collectively, these results support the use of PAZ for weight loss and metabolic and lipid imbalances, and warrant further investigation of the potential effects of ProAlgaZyme on cardiovascular health.

ProAlgaZyme (PAZ) oral algae infusion demonstrated multiple beneficial effects on the various aspects of metabolic syndrome and may significantly promote cardiovascular health in these subjects. ProAlgaZyme was able to reduce body weight and BMI in overweight and obese persons, and trigger an improvement in lipid profile characterized by a decrease of blood total cholesterol, LDL-cholesterol and triglycerides, coupled with an increase in HDL-cholesterol. In addition, the infusion reduced fasting blood glucose and brought about a diminution of markers of inflammation. The infusion was well-tolerated and no side effects were noted in the study. The changes obtained after 10 weeks were significant (p < 0.05 or better). These new findings warrant further exploration into the active components in ProAlgaZyme and its potential newly discovered metabolic and cardiovascular health benefits.

Authors TI, TT, DH and MT declare competing interests. These authors have received salary and/or stocks from Health Enhancement Products, Inc., the company who financed the clinical study above and this manuscript, including the article-processing charge. Authors TT, MT and DH are inventors on patents associated with ProAlgaZyme, the test material used in this study, and these patents have been financed by Health Enhancement Products, Inc.

JO and DM conceived, designed and coordinated the work, as well as drafted the manuscript; EE carried out analytical work; DK carried out analytical and statistical analyses of data; TT participated in the design and editing of the manuscript. All authors have read and approved the manuscript.