Original Study| Volume 22, ISSUE 4, P809-815, April 2021

A Novel Fortified Dairy Product and Sarcopenia Measures in Sarcopenic Older Adults: A Double-Blind Randomized Controlled Trial

Published:October 13, 2020DOI:



      To evaluate the efficacy of daily consumption of fortified yogurt with beta-Hydroxy beta-Methyl Butyrate (HMB) and vitamins D and C on measures of sarcopenia, inflammation, and quality of life in sarcopenic older adults.


      In this 12-week randomized double-blind controlled trial, participants received either yogurt fortified with 3 g HMB, 1000 IU vitamin D, and 500 mg vitamin C in the intervention group (n = 33) or plain yogurt in the control group (n = 33).

      Setting and Participants

      A total of 66 older adults with sarcopenia recruited from the community in Shiraz, Iran.


      Body composition, muscle strength, and functionality were measured using Dual-energy-X-ray Absorptiometry (DXA), hydraulic handgrip dynamometer, and usual gait speed, respectively. Serum concentrations of vitamin D, insulin-like growth factor-1 (IGF-1), C-reactive protein (hs-CRP), malondialdehyde, and insulin were measured at baseline and after 12 weeks. Health-related quality of life (HRQoL) was also evaluated using SF-12 questionnaire.


      Consumption of fortified yogurt was associated with improvement in handgrip strength [mean change (95% confidence interval) 4.36 (3.35–5.37) vs. 0.97 (−0.04 to 1.99)] and gait speed [0.10 (0.07–0.13) vs. 0.01 (0.00–0.04)] in the intervention group compared with the control group (P < .001). In addition, the results revealed a significant increase in vitamin D and IGF-1 levels in the intervention group (P < .001). The nutritional intervention significantly prevented any increase in the serum concentration of hs-CRP compared with the control group (P = .033). The results also showed a more significant decrease in the malondialdehyde level in the intervention group compared with the control (P = .008). Moreover, there were significant differences between the 2 groups regarding physical aspects of HRQoL (P = .035).

      Conclusions and Implications

      A novel dairy product fortified with HMB, vitamin D, and vitamin C not only could enhance muscle strength and functionality, but also modulate anabolic and inflammatory conditions as well as quality of life. This study suggested that specific nutritional interventions alone could be beneficial, especially for those who are unable to exercise.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of the American Medical Directors Association
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Cruz-Jentoft A.J.
        • Bahat G.
        • Bauer J.
        • et al.
        Sarcopenia: Revised European consensus on definition and diagnosis.
        Age Ageing. 2018; 48: 16-31
        • Malafarina V.
        • Úriz-Otano F.
        • Iniesta R.
        • Gil-Guerrero L.
        Sarcopenia in the elderly: Diagnosis, physiopathology and treatment.
        Maturitas. 2012; 71: 109-114
        • Dennison E.M.
        • Sayer A.A.
        • Cooper C.
        Epidemiology of sarcopenia and insight into possible therapeutic targets.
        Nat Rev Rheumatol. 2017; 13: 340
        • Bauer J.M.
        • Verlaan S.
        • Bautmans I.
        • et al.
        Effects of a vitamin D and leucine-enriched whey protein nutritional supplement on measures of sarcopenia in older adults, the PROVIDE study: A randomized, double-blind, placebo-controlled trial.
        J Am Med Dir Assoc. 2015; 16: 740-747
        • Abiri B.
        • Vafa M.
        Nutrition and sarcopenia: A review of the evidence of nutritional influences.
        Crit Rev Food Sci Nutr. 2019; 59: 1456-1466
        • Bell K.E.
        • Snijders T.
        • Zulyniak M.
        • et al.
        A whey protein-based multi-ingredient nutritional supplement stimulates gains in lean body mass and strength in healthy older men: A randomized controlled trial.
        PLoS One. 2017; 12: e0181387
        • Negro M.
        • Perna S.
        • Spadaccini D.
        • et al.
        Effects of 12 weeks of essential amino acids (EAA)-based multi-ingredient nutritional supplementation on muscle mass, muscle strength, muscle power and fatigue in healthy elderly subjects: A randomized controlled double-blind study.
        J Nutr Health Aging. 2019; 23: 414-424
        • Robinson S.M.
        • Reginster J.-Y.
        • Rizzoli R.
        • et al.
        Does nutrition play a role in the prevention and management of sarcopenia?.
        Clin Nutr. 2018; 37: 1121-1132
        • Holeček M.
        Beta-hydroxy-beta-methylbutyrate supplementation and skeletal muscle in healthy and muscle-wasting conditions.
        J Cachexia Sarcopenia Muscle. 2017; 8: 529-541
        • Courel-Ibáñez J.
        • Vetrovsky T.
        • Dadova K.
        • et al.
        Health benefits of β-hydroxy-β-methylbutyrate (HMB) supplementation in addition to physical exercise in older adults: A systematic review with meta-analysis.
        Nutrients. 2019; 11: 2082
        • Scott D.
        • Blizzard L.
        • Fell J.
        • et al.
        A prospective study of the associations between 25-hydroxy-vitamin D, sarcopenia progression and physical activity in older adults.
        Clin Endocrinol. 2010; 73: 581-587
        • Garcia M.
        • Seelaender M.
        • Sotiropoulos A.
        • et al.
        Vitamin D, muscle recovery, sarcopenia, cachexia and muscle atrophy.
        Nutrition. 2019; 60: 66-69
        • Cesari M.
        • Incalzi R.A.
        • Zamboni V.
        • Pahor M.
        Vitamin D hormone: A multitude of actions potentially influencing the physical function decline in older persons.
        Geriatr Gerontol Int. 2011; 11: 133-142
        • Liu Z.
        • Ren Z.
        • Zhang J.
        • et al.
        Role of ROS and nutritional antioxidants in human diseases.
        Front Physiol. 2018; 9: 477
        • Cerullo F.
        • Gambassi G.
        • Cesari M.
        Rationale for antioxidant supplementation in sarcopenia.
        J Aging Res. 2012; 2012: 316943
        • Bo Y.
        • Liu C.
        • Ji Z.
        • et al.
        A high whey protein, vitamin D and E supplement preserves muscle mass, strength, and quality of life in sarcopenic older adults: A double-blind randomized controlled trial.
        Clin Nutr. 2019; 38: 159-164
        • Marty E.
        • Liu Y.
        • Samuel A.
        • et al.
        A review of sarcopenia: Enhancing awareness of an increasingly prevalent disease.
        Bone. 2017; 105: 276-286
        • Nasimi N.
        • Dabbaghmanesh M.H.
        • Sohrabi Z.
        Nutritional status and body fat mass: Determinants of sarcopenia in community-dwelling older adults.
        Exp Gerontol. 2019; 122: 67-73
        • Cruz-Jentoft A.J.
        • Sayer A.A.
        Lancet. 2019; 393: 2636-2646
        • Flakoll P.
        • Sharp R.
        • Baier S.
        • et al.
        Effect of β-hydroxy-β-methylbutyrate, arginine, and lysine supplementation on strength, functionality, body composition, and protein metabolism in elderly women.
        Nutrition. 2004; 20: 445-451
        • Chen L.-K.
        • Liu L.-K.
        • Woo J.
        • et al.
        Sarcopenia in Asia: Consensus report of the Asian Working Group for Sarcopenia.
        J Am Med Dir Assoc. 2014; 15: 95-101
        • Phillips S.M.
        • Martinson W.
        Nutrient-rich, high-quality, protein-containing dairy foods in combination with exercise in aging persons to mitigate sarcopenia.
        Nutr Rev. 2018; 77: 216-229
        • Ehling S.
        • Reddy T.M.
        Investigation of the presence of β-hydroxy-β-methylbutyric acid and α-hydroxyisocaproic acid in bovine whole milk and fermented dairy products by a validated liquid chromatography–mass spectrometry method.
        J Agric Food Chem. 2014; 62: 1506-1511
        • Jafari T.
        • Faghihimani E.
        • Feizi A.
        • et al.
        Effects of vitamin D-fortified low fat yogurt on glycemic status, anthropometric indexes, inflammation, and bone turnover in diabetic postmenopausal women: A randomised controlled clinical trial.
        Clin Nutr. 2016; 35: 67-76
        • Beaudart C.
        • Reginster J.-Y.
        • Slomian J.
        • et al.
        Estimation of sarcopenia prevalence using various assessment tools.
        Exp Gerontol. 2015; 61: 31-37
        • St-Onge M.-P.
        • Wang Z.
        • Horlick M.
        • et al.
        Dual-energy X-ray absorptiometry lean soft tissue hydration: Independent contributions of intra-and extracellular water.
        Am J Physiol Endocrinol Metab. 2004; 287: E842-E847
        • Zal F.
        • Mostafavi-Pour Z.
        • Vessal M.
        Comparison of the effects of vitamin E and/or quercetin in attenuating chronic cyclosporine a-induced nephrotoxicity in male rats.
        Clin Exp Pharmacol Physiol. 2007; 34: 720-724
        • Holick M.F.
        • Binkley N.C.
        • Bischoff-Ferrari H.A.
        • et al.
        Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society clinical practice guideline.
        J Clin Endocrinol Metab. 2011; 96: 1911-1930
        • Lauretani F.
        • Russo C.R.
        • Bandinelli S.
        • et al.
        Age-associated changes in skeletal muscles and their effect on mobility: An operational diagnosis of sarcopenia.
        J Appl Physiol. 2003; 95: 1851-1860
        • Sanz-Paris A.
        • Camprubi-Robles M.
        • Lopez-Pedrosa J.
        • et al.
        Role of oral nutritional supplements enriched with B-hydroxy-B-methylbutyrate in maintaining muscle function and improving clinical outcomes in various clinical settings.
        J Nutr Health Aging. 2018; 22: 664-675
        • Berton L.
        • Bano G.
        • Carraro S.
        • et al.
        Effect of oral beta-hydroxy-beta-methylbutyrate (HMB) supplementation on physical performance in healthy old women over 65 years: An open label randomized controlled trial.
        PLoS One. 2015; 10: e0141757
        • Nishizaki K.
        • Ikegami H.
        • Tanaka Y.
        • et al.
        Effects of supplementation with a combination of β-hydroxy-β-methyl butyrate, L-arginine, and L-glutamine on postoperative recovery of quadriceps muscle strength after total knee arthroplasty.
        Asia Pac J Clin Nutr. 2015; 24: 412-420
        • Olveira G.
        • Olveira C.
        • Doña E.
        • et al.
        Oral supplement enriched in HMB combined with pulmonary rehabilitation improves body composition and health related quality of life in patients with bronchiectasis (prospective, randomised study).
        Clin Nutr. 2016; 35: 1015-1022
        • Baier S.
        • Johannsen D.
        • Abumrad N.
        • et al.
        Year-long changes in protein metabolism in elderly men and women supplemented with a nutrition cocktail of β-hydroxy-β-methylbutyrate (HMB), L-arginine, and L-lysine.
        J Parenteral Enteral Nutr. 2009; 33: 71-82
        • Cramer J.T.
        • Cruz-Jentoft A.J.
        • Landi F.
        • et al.
        Impacts of high-protein oral nutritional supplements among malnourished men and women with sarcopenia: A multicenter, randomized, double-blinded, controlled trial.
        J Am Med Dir Assoc. 2016; 17: 1044-1055
        • Fuller Jr., J.C.
        • Baier S.
        • Flakoll P.
        • et al.
        Vitamin D status affects strength gains in older adults supplemented with a combination of β-hydroxy-β-methylbutyrate, arginine, and lysine: A cohort study.
        J Parenteral Enteral Nutr. 2011; 35: 757-762
        • Gunton J.E.
        • Girgis C.M.
        Vitamin D and muscle.
        Bone Rep. 2018; 8: 163-167
        • Rondanelli M.
        • Klersy C.
        • Terracol G.
        • et al.
        Whey protein, amino acids, and vitamin D supplementation with physical activity increases fat-free mass and strength, functionality, and quality of life and decreases inflammation in sarcopenic elderly.
        Am J Clin Nutr. 2016; 103: 830-840
        • Ascenzi F.
        • Barberi L.
        • Dobrowolny G.
        • et al.
        Effects of IGF-1 isoforms on muscle growth and sarcopenia.
        Aging Cell. 2019; 18: e12954
        • Maggio M.
        • De Vita F.
        • Lauretani F.
        • et al.
        IGF-1, the cross road of the nutritional, inflammatory and hormonal pathways to frailty.
        Nutrients. 2013; 5: 4184-4205
        • Barrera G.
        • Pizzimenti S.
        • Daga M.
        • et al.
        Lipid peroxidation-derived aldehydes, 4-hydroxynonenal and malondialdehyde in aging-related disorders.
        Antioxidants. 2018; 7: 102
        • Song Y.-H.
        • Song J.L.
        • Delafontaine P.
        • Godard M.P.
        The therapeutic potential of IGF-I in skeletal muscle repair.
        Trends Endocrinol Metab. 2013; 24: 310-319
        • Arazi H.
        • Taati B.
        • Suzuki K.
        A review of the effects of leucine metabolite (β-Hydroxy-β-methylbutyrate) supplementation and resistance training on inflammatory markers: A new approach to oxidative stress and cardiovascular risk factors.
        Antioxidants. 2018; 7: 148
        • Liberman K.
        • Njemini R.
        • Luiking Y.
        • et al.
        Thirteen weeks of supplementation of vitamin D and leucine-enriched whey protein nutritional supplement attenuates chronic low-grade inflammation in sarcopenic older adults: The PROVIDE study.
        Aging Clin Exp Res. 2019; 31: 845-854
        • Damiano S.
        • Muscariello E.
        • La Rosa G.
        • et al.
        Dual role of reactive oxygen species in muscle function: Can antioxidant dietary supplements counteract age-related sarcopenia?.
        Int J Mol Sci. 2019; 20: 3815
        • Oktaviana J.
        • Zanker J.
        • Vogrin S.
        • Duque G.
        The effect of β-hydroxy-β-methylbutyrate (HMB) on sarcopenia and functional frailty in older persons: A systematic review.
        J Nutr Health Aging. 2019; 23: 145-150