Chocolate and Physical Exercise to Reduce Malnutrition in Pre-dementia Aged People

Summary

We hypothesize that the antioxidant and cytoprotective functions of vitamin E combined with the cortisol-lowering effect of chocolate polyphenols and physical activity may help prevent the age-dependent decline of mitochondrial function and nutrient metabolism in skeletal muscle, key underpinning events in protein-energy malnutrition (PEM) and muscle wasting in the elderly. To test this hypothesis, a vitamin E functionalized dark chocolate rich in polyphenols will be developed with the collaboration of Nestlè Company, and its effects will be investigated combined with physical activity in a 6-month randomized case-control trial on pre-dementia elderly patients, a well-defined population of subjects at risk of undernutrition and frailty. Subjects stabilized on a protein-rich diet (0.9-1.0 g protein/Kg ideal body weight/day) and physical exercise program (High Intensity Interval Training specifically developed for these subjects), will be randomized in 3 groups (n = 34 each): controls (Group A) will maintain the baseline diet and cases will receive either 30 g/day of dark chocolate containing 500 mg total polyphenols (corresponding to 60 mg epicatechin) and 100 mg vitamin E (as RRR-alpha-tocopherol) (Group B) or the high polyphenol chocolate without additional vitamin E (Group C). Diet will be isocaloric and with the same intake of polyphenols and vitamin E in the 3 groups. Muscle mass will be the primary endpoint and other clinical endpoints will include neurocognitive status and previously identified biomolecular indices of frailty in pre-dementia patients. Muscle biopsies will be collected to assess myocyte contraction and mitochondrial metabolism. Laboratory endpoints will include the nutritional compliance to the proposed intervention (blood polyphenols and vitamin E status and metabolism), 24-h salivary cortisol, steroid hormones and IGF-1, and molecular indices of inflammation, oxidant stress, cell death and autophagy. These parameters will be investigated in muscle and blood cells by state-of-the-art omics techniques. Molecular and nutritional findings will also be confirmed in vitro using skeletal myotubes, blood leukocytes and neural cell lines. Clinical and laboratory results will be processed by a dedicated bioinformatics platform (developed with the external collaboration of the omics company Molecular Horizon Srl) to interpret the molecular response to the nutritional intervention and to personalize its application.

Conditions

• Dementia
• Dementia, Mild
• Dementia Moderate
• Dementia Senile
• Malnutrition
• Deficiency Nutritional
• Deficiency Diseases

Interventions

BEHAVIORAL

Combination of High Protein Diet and Physical Exercise protocol

A high Protein Diet (HPro) will be provided to maintain individual caloric endpoint and to adjust protein intake to 0.9-1.0 g/Kg ideal body weight. Each participant will receive a tailored diet (taking into account personal preference) which will follow common general guidelines. Servings of food high in polyphenols will be limited to one per day. Physical exercise will be undertaken three times each week for about 50 minutes per session. The intervention will consist of both aerobic and strength training exercises. Aerobic exercise will consist of walking on a treadmill with 4 x 4 minutes at (85-95% of HRmax), interrupted by 3-minute active recovery periods (60-70% of HRmax). Strength exercise consists of maximal strength training, using a seated leg press with 4 sets of 4 repetitions at \~90% of maximal strength (1RM). Rest periods between the sets will be 3-4 min.

DIETARY_SUPPLEMENT

HPP Choko

Participants add to their diet with 30 g/day of 85% dark chocolate high in polyphenols

DIETARY_SUPPLEMENT

HPP/VE Choko

Participants add to their diet 30 grams of 85% dark chocolate high in polyphenols, functionalized with 100 mg of Vitamin E per day.

Sponsors & Collaborators

• University Of Perugia

  collaborator OTHER

• Instituto de Investigacion Sanitaria INCLIVA

  collaborator INDUSTRY

• Molde University College

  collaborator OTHER

• University of Liverpool

  collaborator OTHER

• Molecular Horizon S.r.l.

  collaborator UNKNOWN

• Nestlé Italiana S.p.A.

  collaborator UNKNOWN

• Massimo Venturelli, PhD

  lead OTHER

Principal Investigators

• Massimo Venturelli, PhD · Universita di Verona

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

65 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-05-01

Primary Completion

2024-12-30

Completion

2024-12-30

Countries

• Italy

Study Locations