Cardiovascular Health, Cognitive Function Decline, Functional Health, Physical Performance Decline in Older Adults
Conditions
Keywords
beetroot extract, dietary nitrate, cardiovascular health, functional health, quality of life, cognitive function
Brief summary
The increasing number of adults aged 75 years and older highlights the need for effective, low-cost interventions to preserve cardiovascular health, functional independence, and cognitive performance and to support healthy aging. Beetroot extract (BE), derived from "Beta vulgaris", contains high levels of inorganic nitrate and other bioactive compounds that may positively influence vascular and neuromuscular function. In parallel, multicomponent physical exercise is recognized as an effective strategy to improve physical and cognitive outcomes in older adults. However, evidence on the independent and combined effects of BE supplementation and structured exercise in very old adults remains limited. This randomized controlled trial is designed to evaluate the effects of BE supplementation, alone and in combination with a multicomponent physical exercise program, on blood pressure, functional performance, and cognitive function in adults aged 75 years and older. Participants will be randomly assigned to one of four groups: BE supplementation, multicomponent exercise, combined BE supplementation and exercise, or a control condition, over a predefined intervention period. The exercise program will include strength, balance, mobility, and aerobic components specifically adapted to the abilities and safety requirements of old adults. The primary outcomes of the study will assess changes in cardiovascular health, physical and functional performance, and cognitive function using standardized and validated assessment tools. Secondary outcomes will include additional indicators of physical capacity and health-related quality of life. This trial aims to provide clinically relevant evidence on whether BE supplementation, alone or in combination with multicomponent exercise, represents a practical and scalable intervention to improve cardiovascular, functional, and cognitive health in adults aged 75 years and older.
Interventions
DIETARY_SUPPLEMENTBeetroot Extract Supplementation
Participants receive daily supplementation with beetroot extract juice, with or without participation in a multicomponent physical exercise program, depending on group allocation. When applicable, the exercise program targets strength, balance, mobility, and aerobic capacity, and is supervised by trained professionals during the first 6 weeks and subsequently prescribed but not supervised for the following 6 weeks. This intervention aims to evaluate the independent and combined effects of beetroot extract supplementation and physical exercise on cardiovascular, functional, and cognitive outcomes in adults aged 75 years and older.
DIETARY_SUPPLEMENTPlacebo group: nitrate-depleted beetroot juice
Participants receive daily supplementation with nitrate-depleted beetroot juice, with or without participation in a multicomponent physical exercise program, according to group allocation. The placebo juice is derived from beetroot but has had its nitrate content removed, maintaining similar appearance, taste, and texture to the active supplement. When applicable, the exercise program targets strength, balance, mobility, and aerobic capacity and is supervised by trained professionals during the first 6 weeks, followed by a prescribed but unsupervised phase for the subsequent 6 weeks. This placebo-controlled intervention is designed to isolate the effects of dietary nitrate from beetroot extract and to evaluate the independent and combined effects of physical exercise on cardiovascular, functional, and cognitive outcomes in adults aged 75 years and older.
Sponsors
Fundacion Miguel Servet
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Masking description
The professionals delivering the execise interventions are blinded to beetroot extract or placebo allocation.
Eligibility
Sex/Gender
ALL
Age
75 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Adults aged 75 years and older recruited from the Geriatrics Service of the Hospital Universitario de Navarra (HUN) or primary care settings. 2. Ability to ambulate independently. 3. Ability to communicate effectively. 4. Ability to tolerate physical exercise. 5. Barthel Index score greater than 60 points.
Exclusion criteria
1. Refusal or inability of the participant, caregiver, or legal guardian to provide written informed consent. 2. Advanced or severe dementia (Global Deterioration Scale \[GDS\] stages 6-7). 3. Unstable medical condition or terminal illness with a life expectancy of less than 6 months. 4. Ischemic heart disease or congestive heart failure. 5. Severe renal insufficiency. 6. Hypotension.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood Pressure | At baseline - 6 weeks - 12 weeks | Blood pressure (systolic and diastolic) will be measured three times in a row, and the average of the three readings will be calculated. |
| Heart rate | [Time Frame: Baseline - 6 weeks and 12 weeks] | Heart rate will be measured at rest, after the 6-minute walk test, and then 3 minutes after the test has finished. |
| Stroop Test | At baseline - 6 weeks - 12 weeks | This test measures cognitive control and attention by asking individuals to name the color of a word rather than the word itself. It evaluates the ability to manage interference between conflicting information. |
| Symbol Digit Modalities Test (SDMT) | At Baseline - 6 weeks - 12 weeks | This test assesses processing speed, attention, and working memory by requiring individuals to match symbols with corresponding numbers under time pressure. Faster and more accurate performance indicates better cognitive functioning. |
| Trail Making Test - A (TMT-A) | At baseline - 6 weeks - 12 weeks | This test evaluates visual attention and task switching by asking individuals to connect a sequence of numbers (Part A). It measures cognitive flexibility, speed, and executive function. |
| 6 minute walk test (6MWT) | At baseline - 6 weeks - 12 weeks | This test measures functional exercise capacity by assessing how far a person can walk in six minutes on a flat surface. It reflects endurance and helps evaluate cardiovascular, respiratory, and musculoskeletal function. |
| Short Physical Performance Battery (SPPB) | At baseline - 6 weeks - 12 weeks | Physical Function: Assessed using the Short Physical Performance Battery (SPPB), which combines balance, gait velocity, and leg strength as a single score on a 0 (worst) to 12 (best scale) |
| Strength | At baseline - 6 weeks - 12 weeks | Handgrip strength and maximal concentric strength (leg press, chest press, knee extension, seated row machine). Changes in "1RM", defined as the maximum resistance/load a person can move in one repetition of an exercise will be assessed. These values are mesured in Kilograms and results are individualized. |
| Quality of life (QoL) | At baseline - 12 weeks | Measurment of quality of life using EQ5D-3L, the patients indicate their health state by choosing one level for each of the five dimensions, creating a 5-digit code representing 243 possible health states. EQ VAS, includes a vertical Visual Analogue Scale (0-100) where patients rate their self-rated health, with 100 being the "best imaginable health state". Utility. The responses can be converted into a single index value (utility score) using country-specific valuation sets, where 1 represents full health and 0 represents death. |
| Medication Use (Polypharmacy and Psychotropic Drugs) | At baseline - 12 weeks | Number and type of medications will be recorded. Polypharmacy will be defined as the use of ≥5 medications. Psychotropic drug use and medications related to comorbid or intercurrent conditions (e.g., antibiotics) will also be documented |
| Sleep Health Index (SATED) | At baseline - 12 weeks | SATED : This questionnaire assesses sleep health across five dimensions: Satisfaction, Alertness, Timing, Efficiency, and Duration. It provides a brief evaluation of overall sleep quality and habits. |
| Nutritional Status | At baseline | Mini Nutritional Assessment (MNA) ranges from normal nutritional status (24-30points), risk of malnutrition (17-23.5points), or malnourished(\<17points). |
| Barthel Index | At baseline | Barthel Index of independence during activities of dailyliving (ADLs) ranges from 0 (severe functional dependence) to 100 (functional independence). |
| International Physical Activity Questionnaire (IPAQ) | At baseline | This questionnaire measures physical activity levels by asking about the frequency and duration of different intensities of activity. It is used to estimate total physical activity and categorize individuals into activity levels. |
| Mini-Mental State Examination (MMSE) | At baseline | This test is a brief screening tool used to assess cognitive function, including orientation, memory, attention, language, and visuospatial skills. It helps identify cognitive impairment and monitor changes over time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Continuous Glucose Monitoring | During the first 15 days | Continuous Glucose Monitoring (FreeStyle Libre 2): This system measures glucose levels continuously through a small sensor placed on the skin, providing real-time data without frequent finger pricks. It helps track glucose trends and fluctuations, supporting better diabetes management and treatment decisions. |
| Laboratory Parameters: Blood Nitrate and Nitric Oxide Assessment | At baseline - 6 weeks - 12 weeks | Blood Nitrate and Nitric Oxide Assessment: This measurement evaluates nitric oxide (NO) bioavailability by analyzing changes in blood nitrate levels, a stable indirect marker of NO production, typically expressed in µmol/L. . Blood samples (10-20 mL) will be collected alongside routine clinical testing using Vacutainer tubes (EDTA, citrate, or serum tubes as appropriate). Samples will be left upright for 10 minutes and centrifuged at 3000 rpm for 15 minutes to obtain serum and plasma for analysis. Aliquots will be stored at -80°C for future specialised analyses, including flow cytometry. |
| Body Composition by Bioimpedance | At baseline - 6 weeks - 12 weeks | Body Composition by Bioimpedance (BIA 101 BIVA® PRO): This method assesses body composition by measuring electrical impedance through a two-electrode system, providing estimates of body water, fat mass, and fat-free mass. It also uses bioelectrical impedance vector analysis (BIVA) to evaluate hydration status and cellular health, offering insights into nutritional and physiological condition. |
Countries
Spain
Contacts
CONTACTNicolas Martinez-Velilla, Md-PhD
CONTACTFabricio Zambom-Ferraresi, PhD
PRINCIPAL_INVESTIGATORNicolas Martinez-Velilla, MD-PhD
Navarrabiomed-Fundación Miguel Servet-Hospital Universitario de Navarra
Outcome results
None listed