Effect of Spirulina Maxima and Exercise on General Fitness and Blood Lipids in Older Adults

Study Overview
=================
Brief Summary
-----------------
The global older adult population has grown more than any other age group, which could be explained by the decrease of birth rate and increase of life expectancy. The healthy life expectancy of older adult in Mexico is 65.8 years, and the population's life expectancy in general is 74.4 years, this means that the population meeting that age is at increased risk of developing some disease or dependence during approximately nine years of their life. For the population over 60 years, the three most frequent health conditions reported were hypertension (40%), diabetes (24.3%), and hypercholesterolemia (20.4%). In this sense, the search for a healthy lifestyle is necessary, which includes a healthy diet that includes supplementation with nutraceuticals and the daily practice of physical activity. Regarding nutraceutical supplementation, the cyanobacterium Spirulina maxima (S. maxima) is an important source of proteins, carotenoids, phenolic compounds and polyunsaturated fatty acids which have been tested for diverse biological activities such as lipid lowering effects, however, existing studies of effects of S. maxima on body composition, physical function and blood lipid profile in humans, mainly in older adults, have a low level of evidence and absence of adequate experimental designs, so its value as a nutraceutical cannot be assured. The effects of performing systematic physical exercise in older adults have been shown to have positive effects on body composition and blood lipid profile, so in the present study it is proposed to evaluate the synergy presented by a supplement such as S. maxima in a systematic physical exercise program on the body composition, physical function and blood lipid profile of sedentary older adults with excess weight in a randomized, double-blind, crossover, placebo controlled trial.

Detailed Description
-----------------
According to international estimations, there will be an increase in the aging population worldwide; with projections of a growth in the population older than 60 years from 900 million in 2015 to two billion in 2050. This means that the older population will move from 12% to 22% of the global population. In Mexico, in the year 2000, people aged 60 and older represented 6.8% of the total population, and an increase of 28% was expected by the year 2050; and only in Baja California State, there were 183,577 inhabitants 65 yr. old and older (Men = 46.3%, Women = 53.7%). Data from a census in Baja California's cities of Mexicali and Tijuana municipalities in 2015, showed the highest cluster of older adults above 65 yr., especially women. In Tijuana, there were 78,019 inhabitants over 65 years; with a projected population by 2020 of 101,574, and 176,134 inhabitants by 2030. The healthy life expectancy of the Mexican older adult is 65.8 years. This means that if the population's life expectancy in general is 74.4 years, the population meeting that age is at increased risk of developing some disease or dependence during approximately nine years of their life. For the population over 60 years, the three most frequent health conditions reported were hypertension (40.0%), diabetes (24.3%) and hypercholesterolemia (20.4%). These diseases affect all body systems and prevent them from carrying out daily life activities such as walking, eating, preparing or buying food, and bathing, among others. In this sense, the search for a healthy lifestyle is necessary, which includes a healthy diet that includes supplementation with nutraceuticals and the daily practice of physical activity. Regarding supplementation with nutraceuticals, the cyanobacterium S. maxima is an important source of antioxidants, currently associated with cardiovascular protection properties. For centuries it has been cultivated and used as a nutritional supplement due to its content of amino acids and essential fatty acids, vitamin C, vitamin E, carotenoids and phycocyanins. Recently, studies on S. maxima have focused on verifying the biological activity of its components, including hypolipidemic effects. However, most studies have been conducted in animal models, with only a few studies focused on the biological effect in humans. However, most studies have been conducted in animal models, with scarce studies focused on its effects on humans. Previous researches have shown smaller adipose depots, lower blood lipid concentrations, and lower body mass gain in mice administered with a high-fat diet and S. maxima than in an high-fat diet mice control. Some studies have found a decrease in body mass, waist circumference, plasma lipid levels, inflammation, and oxidative stress in hypertensive obese patients with S. maxima supplementation (2 g for three months). However, controlled studies focused on the effect of the administration of S. maxima and a systematic exercise program in humans, have not yet been reported. Studies on the potential effects of nutraceutical supplements are increasing in number. There have been reported the effect of 2 g/day of S. maxima supplementation on 40 hypertension subjects in a double-blind, placebo-controlled randomized trial for three months. After the intervention, they reported a significant reduction of body weight, BMI, and blood pressure in the group supplemented with S. maxima, compared with that of the placebo group. Some investigators studied the effect of Spirulina supplementation (1 g/day) during three months on the body weight, BMI, and lipid profile in patients with dyslipidemia and reported a significant decrease in total cholesterol (TC), triglycerides (TG), and cholesterol associated with low-density lipoproteins (LDL-C). Some Spirulina compounds can reduce the macrophages infiltration into visceral fat and prevent the accumulation of liver lipids, resulting in weight reduction, specifically body fat, and there has been proved the effect of Spirulina supplementation (2 g/day) during two months on the serum lipid profile of 15 patients affected by type II diabetes mellitus, resulting in a significant reduction of TG, TC, LDL-C, and free fatty acid in blood concentrations. By means of a better-structured trial. Many of the beneficial effects of Spirulina are attributed to its nutritional content, but its action mechanisms are poorly understood. Some authors suggest that a possible component responsible of the S. maxima hypolipidemic effect is C-phycocyanin protein, which improves the blood lipid profile. Some authors suggest that C-phycocyanin increases endogenous enzymes activity, scavenging free radicals, and downregulates cofactors in fat metabolism like adenine dinucleotide phosphate. Spirulina hypolipidemic effects can be attributed to the fact that dietary supplementation with the cyanobacteria seems to have decreased the intestinal assimilation of cholesterol, probably because Spirulina compounds bind to bile acids in the jejunum, affecting the micellar solubility of cholesterol before suppressing the cholesterol absorption. However, these studies were conducted in animal models and therefore their results cannot be extrapolated to humans, and clinical studies conducted in humans are still very scarce and appropriate clinical trials are needed to elucidate this. Furthermore, it is known that the practice of systematic physical exercise ameliorates the risk of hypertension, diabetes and hypercholesterolemia, physical exercise of moderate intensity has the best protective effect, mainly due to physiological adaptations. Exercise has been also included as part of multicomponent interventions targeting physical function in socioeconomically vulnerable older adults in rural communities. Korean older adults (n= 187) performed a 24-week program that included group exercise, nutritional supplementation and depression management, among other components. Physical function and depression were measured before and after the intervention, with significant improvements following the intervention. Thus, appropriate exercise programs need to be implemented.

Official Title
-----------------
Effect of a Systematic Physical Exercise Program and Spirulina Maxima Supplementation on the Body Composition, Physical Function and Blood Lipid Profile in Sedentary Older Adults With Excess Weight

Conditions
-----------------
Overweight and Obesity

Intervention / Treatment
-----------------
* Dietary Supplement: Spirulina maxima supplementation
* Other: Wash-out
* Other: Placebo supplementation
* Other: Isoenergetic diet
* Other: Systematic physical exercise program


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Sedentary older adults BMI over 25 kg/m2 Volunteered to participate Exclusion Criteria: Presenting a chronical disease Drinking alcohol Taking diet supplements Presenting an impediment to practicing regular physical exercise Elimination Criteria: Attendance by the subject of < 80% to the physical exercise sessions

Ages Eligible for Study
-----------------
Minimum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: evaluate the synergy presented by a supplement such as S. maxima in a systematic physical exercise program on the body composition, physical function and blood lipid profile of sedentary older adults with excess weight in a randomized, double-blind, crossover, placebo controlled trial. This experimental design was chosen to eliminate inter-individual differences related to Spirulina maxima/placebo
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Spirulina maxima supplementation and exercise group<br>Supplementation with Spirulina maxima (4.5 g/d) with a systematic physical exercise program during 12 weeks, then a 2 weeks washout, to finally proceed to the other treatment during 12 more weeks. During the 26 weeks of study duration every participant will have a personal isoenergetic diet. | Dietary Supplement: Spirulina maxima supplementation<br>* Supplementation with Spirulina maxima (4.5 g/d) in capsules during 12 weeks.<br>Other: Wash-out<br>* 2 weeks washout period to each study subject to avoid any possible carryover effect.<br>Other: Isoenergetic diet<br>* All participants will have a personal isoenergetic diet according to their height, weight, body composition and daily physical activity during 26 weeks<br>Other: Systematic physical exercise program<br>* Participants in the systematic physical exercise program groups will exercise for five days a week. The physical activity program will consist of Monday to Friday chair exercises performed during 24 weeks. The approximate exercise duration will be 40 to 50 min. Each exercise session has an initial or warm-up phase (  10 min), a main physical conditioning phase (  25 min), and a cool-down or relaxation phase (  10 min). The physical activities to select have a metabolic equivalent tasks (METs) considered as moderate, between 3.0 and 6.0 METs. Trained personnel will assist older adults to perform the activities, including articular flexibility using elastic bands, postural and proprioception exercises with materials such as rubber balls, wood sticks, and small sandbags. These activities will be selected according to the deterioration and joint stiffness that the participants could present.<br>|
| Experimental: Spirulina maxima supplementation<br>Supplementation with Spirulina maxima (4.5 g/d) without exercise program during 12 weeks, then a 2 weeks washout, to finally proceed to the other treatment during 12 more weeks. During the 26 weeks of study duration every participant will have a personal isoenergetic diet. | Dietary Supplement: Spirulina maxima supplementation<br>* Supplementation with Spirulina maxima (4.5 g/d) in capsules during 12 weeks.<br>Other: Wash-out<br>* 2 weeks washout period to each study subject to avoid any possible carryover effect.<br>Other: Isoenergetic diet<br>* All participants will have a personal isoenergetic diet according to their height, weight, body composition and daily physical activity during 26 weeks<br>|
| Experimental: Exercise group<br>Systematic physical exercise program during 12 weeks, then a 2 weeks washout, to finally proceed to the other treatment during 12 more weeks. During the 26 weeks of study duration every participant will have a personal isoenergetic diet. | Other: Wash-out<br>* 2 weeks washout period to each study subject to avoid any possible carryover effect.<br>Other: Placebo supplementation<br>* Supplementation with placebo (4.5 g/d) in capsules during 12 weeks.<br>Other: Isoenergetic diet<br>* All participants will have a personal isoenergetic diet according to their height, weight, body composition and daily physical activity during 26 weeks<br>Other: Systematic physical exercise program<br>* Participants in the systematic physical exercise program groups will exercise for five days a week. The physical activity program will consist of Monday to Friday chair exercises performed during 24 weeks. The approximate exercise duration will be 40 to 50 min. Each exercise session has an initial or warm-up phase (  10 min), a main physical conditioning phase (  25 min), and a cool-down or relaxation phase (  10 min). The physical activities to select have a metabolic equivalent tasks (METs) considered as moderate, between 3.0 and 6.0 METs. Trained personnel will assist older adults to perform the activities, including articular flexibility using elastic bands, postural and proprioception exercises with materials such as rubber balls, wood sticks, and small sandbags. These activities will be selected according to the deterioration and joint stiffness that the participants could present.<br>|
| Active Comparator: Control group<br>No systematic physical exercise program and No supplementation during 12 weeks, then a 2 weeks washout, to finally proceed to the other treatment during 12 more weeks. During the 26 weeks of study duration every participant will have a personal isoenergetic diet. | Other: Wash-out<br>* 2 weeks washout period to each study subject to avoid any possible carryover effect.<br>Other: Placebo supplementation<br>* Supplementation with placebo (4.5 g/d) in capsules during 12 weeks.<br>Other: Isoenergetic diet<br>* All participants will have a personal isoenergetic diet according to their height, weight, body composition and daily physical activity during 26 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in body composition | Change in body fat percentage by using air displacement plethysmography and of bioimpedance analysis. | 26 weeks | 
| Changes in functional physical condition | The functional physical condition will be evaluated with the Senior Fitness Test (SFT) | 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lower-body strength | The lower-body strength (SFT-LBS) will be assessed by the 30 s test of getting up and sitting down from a chair. | 26 weeks | 
| Changes in upper-body strength | The upper-body strength (SFT-UBS) will be evaluated by the 30 s arm curl with a dumbbell (men = 8-lb, women = 5-lb). | 26 weeks | 
| Changes in lower-body flexibility | Lower-body flexibility (SFT-LBF) will be assessed by the chair flexion test, where participants slowly flex the hip joint, reaching as much as possible or surpassing the toes. | 26 weeks | 
| Changes in upper-body flexibility | Upper-body flexibility (SFT-UBF) will be assessed by the hands test behind the back. The distance between the tips of the middle fingers will be assessed independently of the alignment of the back. | 26 weeks | 
| Changes in agility | Agility will assessed by the 2.44 m timed-up and go test (SFT- TUG), where participants had to get up of a chair, walk as fast as possible 2.44 m and sit down again. | 26 weeks | 
| Changes in aerobic resistance | Aerobic resistance will be evaluated by the 2-min standing marching test (SFT-marching), where participants had to perform as many repetitions (reps) as possible | 26 weeks |