Aging is associated with an increased inflammation named "inflammageing" and with an altered immune response. Different mechanisms have been proposed to explain the phenomenon of inflammageing and increased oxidative stress: deficiencies in essential amino acids, and some micronutrients have an important impact and may induce immune cell dysregulation. Mitochondrial dysfunction may explain the complex relationship between malnutrition sarcopenia, immune dysfunction and aging. Therefore, a personalized nutritional strategy aiming to improve mitochondrial function, decrease oxidative stress, down-regulate inflammation and restore immunity appears to be a logical approach in order to treat malnutrition and its biological and clinical consequences. MIMOSA will investigate the role of nutritional supplements in rescuing altered mitochondrial function and redox state imbalance.
The study participants will all receive optimal standard care ensuring the optimal protein and energy intakes, with at least 1 g protein per kg body weight and day, and 30 kcal per kg body weight and day (or the measured energy expenditure (EE) value). This will be realized by the daily administration of oral nutritional supplements (ONS) providing whole proteins together with dietary advice \[according with the ESPEN nutrition guidelines. All the patients will receive the standard commercially available product used at CHUV (Resource protein ®, Nestlé) and nutritional counselling (SC). All participants included in this study will receive daily, the oral nutritional supplement (ONS), one sachet and two capsule (for blinding purpose). The intervention nutrients will be delivered as follows: * BCAA: 1 sachet containing 4 g of BCAA (details in Table 1) * Micronutrients: 1 sachet containing 4 g of the micronutrient blend and 2 capsules containing 0.6 g of OMEGA 3 PUFA (details in table 1). The placebos will be delivered like this: -1 sachet containing 1 g of maltodextrin and 2 capsules containing 0.6 g of coconut oil. (detailed in Table 1). The duration of the intervention will be 6 weeks, but at least 4 weeks After enrollment patients will be subjected to evaluation of muscle mass by bioimpedance (BIA), muscle strength will be by handgrip strength and muscle performance by the Short Performance Physical Battery (SPPB). Nutritional status will be evaluated by the Mini Nutritional Assessment short form (MNA-SF), Nutrition Risk screening (NRS) score and Body mass index (BMI). Energy expenditure (EE) will be measured by indirect calorimetry using a canopy. Moreover appropriate experiments will be carried out in order to evaluate mitochondrial bioenergetics, replication, and fusion, as well as of redox state. Analyses of inflammageing and immune-senescence will be done by appropriate lab experiments. Micronutrient status will be measured by ELISA or HPLC and ICPMS respectively. Patients will be evaluated at inclusion, at rehabilitation discharge, and one and two months after rehabilitation discharge. The volume of blood required for the above investigations will be 3 x 30 ml over the 2-month period.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
240
daily administration of oral nutritional supplements (ONS) 1) providing whole proteins together with dietary advice according with the ESPEN nutrition guidelines. All the patients will receive the standard commercially available product used at CHUV (Resource protein ®, nestle) and nutritional counselling (SC) and 4 gram per day of BCAAs mixture. Ratio between the BCAAs will be Leucine/Isoleucine/Valine=2:1:1
daily administration of oral nutritional supplements (ONS) 1) providing whole proteins together with dietary advice according with the ESPEN nutrition guidelines. All the patients will receive the standard commercially available product used at CHUV (Resource protein ®, nestle ) and nutritional counselling (SC) and Vitamin A 1200 mg RE, Vitamin D3 2000 IU, Thiamine B1 100 mg, Cobalamin B12 10 mcg, Ascorbic acid C 200 mg, Iron 30 mg, Selenium 100 mcg, Zinc 20 mg, Omega-3 PUFA 1 g
daily administration of oral nutritional supplements (ONS) 1) providing whole proteins together with dietary advice according with the ESPEN nutrition guidelines. All the patients will receive the standard commercially available product used at CHUV (Resource protein ®, nestle ) and nutritional counselling (SC) and maltodextrin 4 g as placebo
CHUV
Lausanne, Switzerland, Switzerland
RECRUITINGChange in mitochondrial ATP production (nmol/ml)
Production of ATP will be measured using the ATP Bioluminescent Assay Kit
Time frame: change vesus baseline at 30, 60 days after discharge
Change in redox state (plasmatic concentration of metabolites)
analyses of thiometabolome contains: methionine, methionine sulfone, methionine sulfoxide, cysteine, homocysteine, homocystine, cystathionine, formylmethionine, cystine, glutathione, glutathione disulfide, taurine, S-adenosylmethionine, S-adenosylhomocysteine, N-acetylcysteine, cysteic acid, serine, glycine, glutamic acid, lypoic acid, selenocysteine, thioctic acid, pyruvic acid.
Time frame: change vesus baseline at 30, 60 days after discharge
Change in mitochondrial electron flux (nmol cit/min/mg prot)
The activity of Complex I and III will be measured on non-sonicated mitochondrial samples
Time frame: change vesus baseline at 30, 60 days after discharge
change micronutrients status (concentration of micronutrients)
Blood levels of Vitamins A, B12, D and E, as well as of trace elements Cu, Fe, Se, and Zn will be determined by ELISA or HPLC and ICPMS
Time frame: change versus baseline at 60 days after discharge
change in inflammation
Production of pro-inflammatory cytokines involved in inflammageing and in muscle waste will be measured by ELISA technique; we will measure IL-6 and TNF-alpha (pg/ml).
Time frame: change versus baseline at 30, 60 days after discharge
change phase angle (score)
Bioelectrical impedance analysis (BIA) will be carried out
Time frame: change versus baseline at rehab discarge (21 days), 30, 60 days after discharge
muscle function (score)
Short performance physical battery will be used to measure muscle performance
Time frame: change versus baseline at rehab discarge (21 days), 30, 60 days after discharge
muscle mass (Kg/body weight)
Bioelectrical impedance analysis (BIA) will be used to measure muscle mass
Time frame: change versus baseline at rehab discarge (21 days), 30, 60 days after discharge
muscle strength (Kg)
Hand grip will be used to measure muscle strenght
Time frame: change versus baseline at rehab discarge (21 days), 30, 60 days after discharge
change in perceived health status (score)
questionnaire
Time frame: change versus baseline at rehab discarge (21 days), 30, 60 days after discharge
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