Low-Molecular Collagen Peptide Supplementation and Body Fat Mass in Adults Aged ≥ 50 Years: A Randomized, Double-Blind, Placebo-Controlled Trial

Adipose tissue is a metabolically dynamic and endocrine organ and is well known for its function in energy storage and mobilization according to nutrient availability and body needs [1]. It is the largest endocrine organ in the human body, can secrete hormones and inflammatory molecules, and has an important effect on multiple processes such as adipogenesis, metabolism, and chronic inflammation [1, 2]. Therefore, the expansion of adipose tissues, particularly the visceral, causes low-grade inflammation, which contributes to insulin resistance and dyslipidemia [2, 3]. Normal aging involves important changes in the body composition, including decreased muscle mass and increased fat mass [4]. With aging, the body’s muscle mass steadily decreases by 1%–2% annually after the age of 50, and the resulting decrease in the basal metabolic rate induces body fat mass and weight gain [5, 6]. Age-related changes contribute to age-related diseases such as cardiovascular events, diabetes mellitus, hypertension, and several types of cancer [7]. As body fat mass peaks at the age of 65–70 years [4], materials with anti-adipogenic effect must be developed and discovered from naturally available sources for the middle-aged population.

Collagen is the most representative protein in the human body, accounting for 30% of body protein [8]. Specifically, it is the primary structural protein of connective tissues and is ubiquitous within the extracellular matrix of skeletal muscles and tendons [9]. Recently, many products, such as cosmetics or food, containing collagen or denatured collagen, have been widely used for various purposes [10]. Collagen peptides, which are hydrolyzed from natural collagen, have a high absorption rate and are used as a bioavailable food supplement without any side effects [11, 12]. Improving skin quality, including hydration, elasticity, and visibility of wrinkles, is one of the best known benefits of collagen supplementation [13]. Recently, benefits from hydrolyzed collagen were also reported on lesion prevention, tissue repair, weight loss, and increase in fat-free mass (FFM). [14]. In randomized controlled trials, Zdzieblik et al. [7] announced that 15 g of collagen peptide supplementation reduced the body weight and body fat mass in older sarcopenic men. Then, they [15] reported that the intake of specific bioactive collagen peptides (15 g/day) significantly decreased the body fat mass, body weight, and waist circumference following resistance training in middle-aged, untrained men. Jendricke et al. [16] found that specific collagen peptides (15 g/day) in combination with resistance training improve body fat mass in premenopausal women. However, collagen supplementation further enhances the positive effects of resistance training and does not show the effect of collagen supplementation alone.

Those who are not accustomed to exercise training may need more management of body fat mass. However, resistance training in untrained older adults is difficult and increases the risk of falls and fall-related injuries [17]. Several preclinical studies have reported the anti-obesity effect of collagen protein to the reduction of adipogenic differentiation by regulating peroxisome proliferator-activated receptor-γ (Pparγ) and CCAAT/enhancer binding protein-alpha (C/EBPα) expression [18, 19]. Tak et al. [20] reported that the anti-obesity effect of collagen intake was evident even without resistance training. Moreover, intake of low-molecular collagen peptides for 12 weeks reduced the percent body fat in overweight adults; however, no difference in body weight, body mass index (BMI), or fat mass was found. Although they confirmed the effect of 2 g of collagen intake per day, many studies [7, 15, 16] have reported that consuming at least 15 g of collagen per day has clinical effects.

This clinical trial was conducted to confirm whether collagen peptide supplementation has a beneficial effect on body fat control in older adults with daily physical activity level. This study aimed to evaluate the effect of collagen peptide supplementation (15 g/day) for 12 weeks on body fat in older adults aged ≥ 50 years.

The clinical trial evaluated whether collagen peptide supplementation has a beneficial effect on the changes in the body fat of older adults without resistance training. The results confirmed that collagen peptide intake (15 g/day) for 12 weeks had a beneficial effect on body fat reduction, including abdominal fat, in older adults aged ≥ 50 years with daily physical activity level.

Collagen has a relatively low biological value, mainly due to the low amounts of branched chain amino acids and lysine [22]. However, it has an excellent amino acid composition and contains relatively high amounts of arginine and glycine, which are important for the synthesis of creatine in the human body; thus, interest in collagen supplementation has recently drawn attention to the possibility of body composition control [7, 14]. Several recent randomized controlled trials [7, 15, 16] have reported that collagen peptide supplementation reduces body fat mass. However, these are not the only effects of collagen supplementation by consuming collagen peptides intake after resistance exercise training during the intervention period. Zdzieblik et al. [7] reported that collagen peptide supplementation (15 g/day) in combination with resistance training increased FFM and reduced body fat mass in older people with sarcopenia. They [15] also announced that specific bioactive collagen peptides (15 g/day) combined with resistance exercise training significantly improved FFM and SMM and decreased the body fat mass, body weight, and waist circumference in middle-aged men. Jendricke et al. [16] found that specific collagen peptides (15 g/day] in combination with resistance training improve FFM and reduced body fat mass in premenopausal women. That is, FFM and SMM was increased with the intake of collagen, a protein, after resistance exercise, and the body fat mass was decreased together.

Recent preclinical studies have found the anti-obesity effect of collagen peptides through the suppression of body fat accumulation and regulation of lipid metabolism [18, 23]. Astre et al. [19] reported an anti-adipogenic effect of collagen peptides on in vitro and in vivo models. They found that collagen peptide intake prevents lipid accumulation in adipocytes by suppressing the expression of adipogenic master transcription factors such as Pparγ, C/EBPα and adipocyte protein 2 genes, which mainly regulate the differentiation and maintenance of adipocytes [19, 23]. The collagen utilized in the clinical trial was a hydrolyzed low-molecular collagen peptide extracted from porcine, which closely resembles human collagen [22] and comprises functional peptides that demonstrate physiological activity. To date, only one clinical trial evaluated the effect of collagen intake on body composition changes, particularly body fat mass without resistance training. The trial evaluated the effect of 2 g low-molecular collagen intake derived from skate skin for 12 weeks on body fat changes in obese adults [20]. The results revealed that collagen supplementation significantly lowered body fat, but did not affect on body weight, BMI, or sagittal abdomen distance. The intake of 2 g/day of collagen may be insufficient to induce clinical effects; thus, this clinical trial was conducted with 15 g, which is the concentration currently used in many collagen studies [7, 14, 15]. As a result, significant decreases were shown in body weight, BMI, WHR, and abdominal fat mass in older adults aged ≥ 50 years with daily physical activity level.

Changes in body composition are well-known representative age-related changes [4]. With age, FFM and SMM decrease, leading to lower basal metabolic rate, which increased body fat [5, 6]. These changes are a major cause of the increasing incidence of cardiovascular diseases, type 2 diabetes, metabolic syndrome, and various cancers in older adults [7]. They are very interested in reducing body fat for health, but have a high risk of injury, so they cannot rely on exercise to change body composition. Older adults prefer to maintain familiar meals and find it difficult to change their eating habits [24]. Therefore, even if for health, there may be limitations in adapting an unfamiliar 'healthy diet' and maintaining intake. Older adults need a safe and convenient way to manage body fat mass while maintaining their usual physical activity and diet, therefore products must be developed and their effectiveness need to be verified. The collagen peptides used in the clinical trial is a safety-secured product, and it influences body fat reduction in the older adults without exercise. This can be a safe and effective method for older people who want to lose body fat. A decrease in food intake is another change with aging, which is often accompanied by decreased appetite and ability to eat [24, 25]. Poor appetite, dysphagia, or chewing difficulty is a very prevalent condition in older adults, affecting approximately 30% of older people. With aging, the food intake of older adults decreases [26]; however, the recommended amount of protein increases [27, 28]. At this time, protein supplementation can be a good strategy. In the results, the collagen group showed an increase of approximately 10 g in protein intake at 12 weeks compared with the baseline, and no difference in the placebo group was found before and after the test. This means that collagen peptide supplementation is effective not only in managing body fat but also in meeting recommended protein intake in older adults.

Arginine and glycine, amino acids that play important roles as precursors for creatine synthesis in the body, are abundant in collagen [7]. Creatine is present in high concentrations in skeletal and cardiac muscles [29], which can be synthesized through the metabolism of glycine, arginine, and methionine [30]. With age, intake of protein (amino acids) tends to decrease, and people may experience vitamin deficiencies [31]. This means that the creatine synthesis may be a particular burden for older adults [30]. Thus, collagen, which is rich in arginine and glycine, could be a more suitable form of protein supplementation for older people. The collagen utilized in the study was a hydrolyzed low-molecular collagen peptide extracted from porcine, which closely resembles human collagen [32]. The beneficial effects of consuming hydrolyzed collagen are closely linked to metabolic peptides that have undergone degradation in the digestive tract [33]. Collagen peptides with low-molecular size are rapidly absorbed from the gastrointestinal tract also in peptide form. In addition, collagen peptides could act as signal messengers in anabolic cellular processes cartilage, tendons, and ligaments, which might help improve painful symptoms of degenerative diseases in older people.

This study has several limitations. The intake time of collagen supplements by the participants was different. The timing of protein supplementation is crucial for FFM synthesis, and the daily protein intake must be effectively distributed evenly between meals rather than consuming it after meals. The subjects were instructed to take the supplements between meals, however, subjects just used their most convenient time to consume supplements daily. Therefore, the timing of supplement intake may have been insufficient for FFM synthesis. Also, we assumed that the body fat changes were attributed to the collagen consumption, but, we could not exclude the possibility that the effect was merely the effect of the extra protein consumption.

Despite these limitations, this study has several advantages. First, this is one of the few studies that have investigated the effects of collagen peptide supplementation alone, without altering participants’ physical activity levels or eating habits. Let alone, we found a positive effect on body fat mass reduction. Second, the participants of this study showed high intake compliance (> 90%). Therefore, with this, we may suggest taking a collagen drink can be a simple method that have a positive effect on changes in body composition after middle age, when body fat increases and physical activity tends to decrease.

In conclusion, this clinical trial evaluated whether collagen peptide supplementation (15 g/day) for 12 weeks has a beneficial effect on body fat changes in older adults even without resistance training. The results confirmed that collagen peptide intake had a beneficial effect on body fat reduction, including abdominal fat, in older adults aged ≥ 50 years with daily physical activity level. This finding might suggest that collagen peptide supplementation has a positive effect on age-related changes by body fat mass reduction.