Urinary titin represents an exciting biomarker for assessment of muscle health

Abstract

Titin is the largest known protein in the human body and operates as a signaling hub, contributes to passive force in the muscle, and as a molecular spring. Muscle tissue experiences damage and atrophy for many reasons including exercise, disease, or age. When muscle tissue is catabolized, a consistent biomarker can be found in the urine: urinary titin N-terminal fragment (UTF). This biomarker was first identified in 2014, but research into this biomarker began in earnest in 2016 when UTF was found to be elevated in both Duchenne muscular dystrophy patients and individuals post-exercise compared to the control groups. Subsequent research found that while Duchenne muscular dystrophy has increased UTF values, this symptom is common across many muscular dystrophy disorders. It’s been postulated that UTF values could be an effective diagnostic tool for early muscular dystrophy disorders and certain forms of myopathy. Both muscle atrophy and eccentric exercise have both been shown to produce elevated UTF as well. This review highlights the key findings over the past 10 years in this field and identifies questions regarding production of UTF that should be the focus of the next 10 years of work in this area.

Background

Titin, also known as connectin, is the largest known protein in the human body. It spans the entirety of the M-line to the Z-disk within the sarcomere of the muscle and also binds to the thick filament the A-band region. Titin is referred to as the molecular spring for its role in muscle contraction (Wang et al. 1993), but it also serves as a signaling hub for various muscular proteins (Nishikawa et al. 2020) and as a source of passive force (DuVall et al. 2017). During exercise or as a symptom of disease, skeletal muscle is broken down through proteolysis, regulated by numerous enzymes and somatic systems to produce protein fragments that can be broken down further or eliminated as waste products (Pasiakos and Carbone 2014). Among the urinary waste products is a fragment of the N-terminus of titin. Since its identification in 2014, there have been a number of studies correlating physiological response with appearance of the 25 kDa urinary titin N-terminal fragment (UTF). The goal of this review is to compile this research into a comprehensive review of our current understanding of the conditions which affect the concentration of UTF in the samples.

This review refers to the biomarker UTF with great regularity, so it is necessary to outline the nature of this biomarker. The biomarker measured in most articles is the human UTF, a 25 kDa fragment that spans the first residue of human titin to the 200th and appears with regularity in urinary samples (Maruyama et al. 2016; Rouillon et al. 2014; Wang et al. 1993; Nishikawa et al. 2020). Muscle protein fragments enter the urine whenever an instance of muscle proteolysis occurs such as exercise tearing muscles or muscle atrophy from disuse. Table 1 provides a summary of some of the studies that have been conducted on UTF.

Table 1.

Summary of UTF values from various studies

Title	Authors	Year	Study group (pmol/mg Cr)	Study Group description	Control Group	Control group description
Changes in Muscle Shear Modulus and Urinary Titin N-Terminal Fragment after Eccentric Exercise	Inami et al.	2022	151.3 ± 178.7	17 healthy males 96 h after performing a strenuous bicep exercise	2.2 ± 1.2	17 healthy males UTF values prior to any exercise
Diagnostic and clinical significance of the titin fragment in urine of Duchenne muscular dystrophy patients	Awano et al.	2018	965.8 ± 1011.9 171.2 ± 272.7	113 Duchenne muscular dystrophy patients and 36 Becker muscular dystrophy patients respectively	1.4 ± 0.8	9 healthy children
A sandwich ELISA kit reveals marked elevation of titin N-terminal fragment levels in the urine of mdx mice	Shirakawa et al.	2022	5326.5 ± 1721.8	7 mdx (muscular dystrophy induced) mice	10.8 ± 6.8	8 healthy mice
The N-Terminal Fragment of Urine Titin Is Not a Product of Degradation by Calpain 3	Nambu et al.	2024	112.3 [IQR]: 81.03–144.3 212.55 [IQR]: 111.95–486.23	2 patients with limb-gridle muscular dystrophy type 1, and 11 patients with other forms of limb girdle muscular dystrophy	N/A	9 healthy individuals were tested but results were not listed
Urinary titin as a biomarker in Fukuyama congenital muscular dystrophy	Sato et al.	2021	455.5 ± 243.9	18 FMD patients	N/A	None used

Enzymatic catabolism

UTF is catabolized by muscle-specific enzymes. For eleven years it was believed for that calpain-3 was the enzyme responsible for this fragment (Rouillon et al. 2014). This 2014 paper examined urinary samples from five Duchenne muscular Dystrophy (DMD) patients to develop an understanding of their proteome and indicated that Calpain-3 was likely involved in proteolysis of the C-terminus, and matrix metalloproteinase (MMP)−9 was involved in proteolysis at the N-terminus (Rouillon et al. 2014). Modern analysis has confirmed that MMP-9 is necessary for titin degradation, although the paper also suggests that MMP-2 and − 12 are also likely involved (Nambu et al. 2025). This has provided some insights into the source of UTF, but more characterization is necessary to really understand its production.

Muscle catabolism between age groups

Infants are a group that are infrequently observed with regards to UTF values despite them having elevated UTF values compared to adults. One study focused on early childhood levels of UTF examined catabolysis in infants, up to 60 weeks old to determine if there are noticeable differences between preterm and term infants. They used UTF values to illustrate that infants falling under the qualifiers: full, late, and moderate preterm infants had comparable values, but infants born after less than 31 weeks had significantly higher UTF values, these being very and extremely preterm infants as described in the article. The comparable grouping was 12.5, 8.1, and 12.8 pmol/mg/dL Cr respectively versus 26.4 pmol/mg/dL in the very preterm infants, and 81.9 pmol/mg/dL in the extremely preterm group (Fukushima et al. 2022). This study is also the first one to assess typical UTF values in infants, noting that infants have much higher baseline UTF values than their older counterparts.

UTF was also used in a study to explore the catabolism of muscle in pre- vs. post-menopausal women using various techniques. The authors compared UTF samples pre- and post-one rep max test to assess strength and catabolism. A one-rep max is the largest amount of weight a person can lift and still complete one repetition of a movement, for this study they did a one rep max for chest press and seated leg press. They found that post-menopausal women had nearly double the UTF concentration than the pre-menopausal women. The findings indicated that the lowered estrogen of menopause resulted in increased inflammatory markers and decreased muscular activation, which likely resulted in higher proteolysis and elevated UTF values in the post-menopausal women (Willoughby et al. 2024). The UTF values reported here are from a much less common UTF evaluation kit (MyBioSource Cat# MBS762344) which reports values in the form of ng/mL and uses proprietary anti-human antibodies.

Previous biomarkers

The first paper to draw parallels between serum creatine kinase (CK), an established marker of muscle damage, and UTF was in 2014 (Rouillon et al. 2014). It was found that titin fragments were elevated in muscular dystrophy patients and this elevation was more sensitive to the level of damage than serum CK (Rouillon et al. 2014). Serum CK has been the choice biomarker for analyzing skeletal muscle damage since it was exclusive to skeletal muscle and was only released into the blood after cellular membrane disruption (Baird et al. 2012; Clarkson et al. 2006; Yamaguchi et al. 2020a; DuVall et al. 2017; Rouillon et al. 2014; Boehler et al. 2024). However, serum monitoring is more invasive and requires specific training to collect compared to urine sampling, making UTF a potentially easier biomarker to monitor compared to serum CK. While UTF may not completely replace serum CK in the future, the high correlation that has been shown between the two values (Yamaguchi et al. 2020a; Tanabe et al. 2021; Awano et al. 2018; McHugh 2003; Nakanishi et al. 2021; Nakano et al. 2021a, b), has resulted in many more recent studies relying only on UTF values.

Measurement of UTF

The majority of studies discussing UTF have relied on sandwich ELISAs such as studies that observe UTF value changes in exercise, atrophy, myopathies, dystrophies, supplementation, and athletics (Nakano et al. 2021a, b; Hyodo et al. 2024; Ishihara et al. 2021; Maruyama et al. 2016; Tanabe et al. 2021; Yamaguchi et al. 2020a, b). An anti-titin capture antibody is attached to the plate and then the sample is incubated in the plate, and any N-terminal titin is captured by this antibody. A second anti-titin antibody is then used to detect any bound titin, either using an anti-titin antibody directly conjugated to horseradish peroxidase (HRP) or using an anti-mouse secondary with HRP conjugated to the anti-mouse antibody (Nambu et al. 2025; Shirakawa et al. 2022; Maruyama et al. 2016; Kanda et al. 2017). This approach provides a quantitative readout of titin levels and has been developed into a commercial kit. A majority of the articles discussed in this review use that commercial kit, now sold by Immuno-Biological Laboratories (IBL) under the title “Human Titin N-Fragment (Urine) ELISA”.

One factor that is important to control for in this assay is the hydration level of the individual since the urine becomes more concentrated the more dehydrated an individual becomes. The standard method for evaluating UTF is correcting for creatinine as this biomarker scales with muscle activity, is accessible via the urine, and will experience equivalent dilution as the UTF. For this reason, most studies have reported the UTF/creatinine ratio by dividing the UTF concentration (pmol/L) by the creatinine level (mg/dL) to get a ratio of the two markers. This ratio provides a corrected value that can be used to compare values between individuals. To better understand the values described later in this article, the average value for adult individuals is roughly 1–3 pmol/mg Cr.

Duchenne muscular dystrophy

UTF values were first characterized in the paper by Maruyama et al. which established the modern day ELISA method for measuring UTF (Maruyama et al. 2016). That study also concluded that UTF was elevated in both tested DMD patients when compared to the control group, but there is a high degree of standard deviation between the two (Maruyama et al. 2016; Pasiakos and Carbone 2014). A follow-up paper categorically demonstrated that UTF values are significantly elevated in a much larger group of DMD patients, showing that those with DMD have an average UTF value of 965 pmol/mg Cr, which was 700 fold higher than their control group samples (Awano et al. 2018). Research in mice would identify the same pattern in mdx mice, which are genetically designed to mimic human DMD (Shirakawa et al. 2022) and these findings were further supported in mice with added human dystrophy genes (Hiramuki et al. 2025). One additional study combined results from humans, mdx mice and Dmd^mdx rats and showed similar results but the nature of the assay they used makes direct comparison to other studies difficult (Robertson et al. 2017).

Other dystrophy disorders

There are numerous other dystrophin disorders with elevated UTF values including Becker muscular dystrophy (BMD) (Hoffman and Kunkel 1989; Mah et al. 2014), limb-girdle muscular dystrophy (LGMDR) (Wicklund and Kissel 2014), Fukuyama congenital muscular dystrophy (FMD) (Toda et al. 2000), and myotonic dystrophy 1 (DM1) (Udd and Krahe 2012). Urinary titin in BMD is not as well researched as DMD, but compared to the other listed dystrophy disorders, it has been investigated in more articles. Findings indicated that BMD patients had an average of 171 pmol/mg Cr, higher than the 1.2 pmol/mg Cr in the control group (Awano et al. 2018). A follow-up study confirmed the elevated UTF values while examining muscle capabilities in BMD patients (Awano et al. 2025). A single study has examined UTF levels in LGMDR and found that these patients had elevated UTF levels relative to controls, similar values to their BMD counterparts (Nambu et al. 2025). FMD patients indicated an average of 455 pmol/mg Cr (Sato et al. 2021; Maruyama et al. 2016). DM1 patients had an average of 39.3 pmol/mg Cr, the lowest out of any dystrophy disorder, though still significantly higher than controls (Varga et al. 2023). In summary, dystrophin disorders do result in larger UTF values compared to healthy controls, but each value reported had high standard deviation so, while no dystrophy patients were close to control values, there is a high degree of error between individual values. It has been postulated that the pattern of dystrophy disorders resulting in elevated UTF values is likely due to the increase in passive muscle damage accrued by individuals with these disorders (Andrew et al. 2024).

It has been proposed that UTF values could represent a potential method for diagnosing a dystrophy disorder in young children. In a study of 100 healthy three-year-old children (52 male, 48 female) versus four DMD children, the UTF values for the DMD children were significantly higher than their healthy counterparts, suggesting a clinically significant difference might exist (Matsuo et al. 2018). This study has yet to be repeated and although earlier screening for dystrophy disorders may end up being important in the future, further research is necessary before UTF values can be used as a diagnostic tool.

A case study has been done using BMD as well, examining its physiologic presentation in two brothers. Despite similar environment and genetic backgrounds, the elder brother has worse symptomology, exhibiting consistently higher UTF and serum CK values despite their 1 year age difference (Nambu et al. 2024). It is theoretically possible that these differences are simply due to age, but the data does not indicate that the brother is simply behind in the advancement of the disease, it appears that he is having less severe symptomology despite the same mutation (Nambu et al. 2024).

UTF values in dystrophy treatment

An exciting potential use for UTF is for assessment of muscular dystrophy treatment plans. A recent study used UTF to assess the effectiveness of a new potential therapeutic agent. After treating patients with this compound, there was a significant decrease from baseline UTF values for up to 360 days after therapeutic admission, although this decrease does not put the DMD patients at comparable levels to the healthy control groups (Boehler et al. 2024). In one group this correlated well with serum CK levels being reduced, while in the other group CK went up by day 365 (59). This study demonstrated the potential of UTF as a screening tool for new therapeutic compounds for treatment of muscle diseases, although this compound does require further analysis before widespread use.

Muscle atrophy

Muscle atrophy is the loss of muscle mass due to immobility or otherwise lack of use which may result in increased levels of UTF due to catabolism, though this still has not been fully established. A study focused on establishing a link between UTF levels and sarcopenia found a negative correlation between age or illness related muscle mass degeneration and UTF values, suggesting muscle atrophy might have similar correlation (Oshida et al. 2019). A case study of an individual who required venous attenuation for oxygenating their tissues had elevated UTF values ranging from 24 to 38 pmol/mg Cr, attributed to the patient’s inactivity (Nakanishi et al. 2020). However, it is important to consider that the UTF values could have also spiked as a result of significant tissue trauma from the infection and venous attenuation in this study, making the link to atrophy and UTF tenuous. A large scale examination was performed on individuals with ICU-acquired weakness, finding elevation in individuals admitted to the ICU throughout the testing period, correlating with rectus femoris muscle mass loss (Nakanishi et al. 2021), further supporting this link.

The most convincing link between muscle atrophy and UTF levels is from a study that examined UTF levels under a series of catabolic conditions (Hyodo et al. 2024). The authors examined UTF level responses in mice after dosing with cardiotoxins for myolysis, casting their limbs for immobilized atrophy, lipopolysaccharide to replicate sepsis, and induced type II diabetes to correlate UTF responses over time under a range of conditions. The results of this study demonstrated that muscle breakdown due to treatment with cardiotoxin, causes an immediate increase in UTF values whereas atrophy may begin to cause UTF elevation more gradually than the immediate results from cardiotoxin (Hyodo et al. 2024). There was a significant increase in UTF values to roughly 150 pmol/mg/dL by hour 10 following immobilization (Hyodo et al. 2024). By comparison, sepsis causes an increase within 24 h, diabetes within 5 days, and the cardiotoxin was within 4 h (Hyodo et al. 2024).

Contrary to the previous study, a study using denervated mice to induce atrophy found no significant difference between the denervated mice and the control mice (Tanihata and Minamisawa 2023). They also found no cell membrane disruption and concluded the UTF could not be extruded if the membrane was remaining intact (Tanihata and Minamisawa 2023). While these results seem contrary, it is possible that the tissue damage induced by cutting the mice during surgery to access and denervate the nerve was responsible for the UTF elevation. Immobilization would have been an optimal atrophy model as this limits any surgically induced muscle damage. At the moment, the correlation between UTF levels and muscle atrophy is inconclusive and further work in this area is necessary to establish this potential link.

Exercise and muscle damage

Exercise induced muscle damage (EIMD) is one of the more common sources of muscle damage examined in studies of UTF. Maruyama et al. examined UTF values for comparison in DMD patients, but they also examined individuals pre- and post-exercise against healthy individuals who are not exercising (Maruyama et al. 2016). Their study was the first to report that EIMD resulted in a UTF value increase. Subsequent groups found that concentric exercise does not significantly alter UTF values (Yamaguchi et al. 2020a; Matsuo et al. 2018), but eccentric exercise, peaking at 96 h post-exercise, does significantly increase UTF values (Inami et al. 2022; Yamaguchi et al. 2020a, b).

This led to the question of whether UTF values are affected by the repeated bout effect (RBE). The repeated bout effect is a phenomena where a single bout of eccentric exercise has a protecting effect on subsequent bouts of that exercise (McHugh 2003). Studies into this question have found that UTF values during the second bout of eccentric exercise are significantly lower than the first bout (Yamaguchi et al. 2020a; Willoughby et al. 2024), consistent with the protective effect that RBE is thought to produce. Lee et al. have found strong correlations between UTF values and EIMD markers like serum CK and myoglobin (Lee et al. 2021), further supporting the use of UTF to assess muscle damage. However, it is important to highlight that they used a different ELISA method, with different antibodies from the ones commonly used in the Maruyama et al. (2016) paper, to obtain their data, and their calculations are unique, which makes inter-article comparison difficult.

Athletes

Since EIMD contributes to UTF value increases, this raises the natural question of whether athletes experience any unique patterns in their UTF levels. Serum CK and UTF values were examined side-by-side in collegiate soccer players and the results indicated that both markers increased up to a peak after 24 h, then returned to baseline by 48 h following a competitive soccer match (Tanabe et al. 2021). The correlation between UTF levels and severe muscle injuries in professional soccer players has also been examined in literature. It was discovered that there is a higher percentage increase of UTF values from baseline in individuals who have had severe injuries in the past compared to individuals who have not experienced a previous injury (Kawai et al. 2021). These findings indicate that previous muscle injury can have an effect on present muscle injury, present in the UTF values. Further research on this subject could help enable UTF values as a muscular injury predictive tool.

UTF value as a facet of biomarker screening

UTF values being established as a biomarker of muscle health provides an opportunity for UTF to be used in a panel fashion with other biomarkers to assess the bodily reaction to a particular stimulus. For example, it has been shown that within 30 min following a three-kilometer run, several organ damage markers were increased but UTF was not one of them (Tominaga et al. 2021). This seems contradictory to other studies, but UTF values observed 30 min after exercise will not necessarily increase considerably from baseline compared to later times (Maruyama et al. 2016; Yamaguchi et al. 2020a, b), so it is possible that there could be elevated levels if UTF levels were evaluated at later time points.

Unfortunately, UTF values have not proven to be the catch-all for muscle-related issues. One example is a study that attempted to use UTF to develop criteria for skeletal muscle mass loss associated with interstitial lung disease. The study found no correlation between disease severity and UTF values, and no correlation between physical performance and UTF values (Hanada et al. 2023). Therefore, UTF would not serve as an effective biomarker for this disease state.

UTF in supplement research

Supplements and vitamins are commonly used to enhance muscle health and recovery following exercise, which could influence UTF levels. One supplement used with older (> 70 years old) trauma patients is beta-hydroxy-beta-methyl butyrate (HMB), a compound found in wasabi (Nakano et al. 2021a, b). In exploring the effects of HMB, UTF values as well as muscle mass remained unaffected by the HMB treatment, although they found that on day 3 the UTF values spiked for individuals who became critically ill (Nakano et al. 2021a, b), though this spike was potentially a consequence of the coming illness causing some muscle damage, or atrophy. Similarly, a study examined curcumin, a compound suggested to reduce inflammation, at 180 mg/day, the researchers were interested in changes in inflammatory markers and muscle damage markers, like UTF, but they found no significant changes from the use of curcumin (Daniel Vasile et al. 2024; Tanabe et al. 2024).

UTF values are still valuable with regards to assessing therapeutics as many individuals seek to reduce muscle damage in individuals or athletes with a compound, and UTF values give a noninvasive metric for that damage. For example, compounds like 6-(Methylsulfinyl)hexyl Isothiocyanate (MSITC) was examined because previous work indicated MSITC reduced calpain-1 activation. The dosage of 9 mg/day of MSITC was not enough to alter calpain-1, inflammation, nor muscle damage markers which includes UTF (Tanabe et al. 2022). Additionally, UTF was used to examine changes in muscle damage with regards to hyperimmunized milk, which was found to have little to no effect on muscle damage, or the inflammatory responses (Ma et al. 2020). It should be remembered that UTF values have not been identified as correlated with inflammatory responses nor markers and were only used in the previously described studies to evaluate muscle damage. Moreover, the whey protein from grass fed cows was examined in a similar article, determining if the effects of EIMD could be attenuated better with whey protein from a grass fed cow than placebo, but the results indicated no meaningful difference between the protein and placebo (Barenie et al. 2024).

Myopathies

Myopathies frequently alter UTF values, meaning this biomarker has the potential to be a tool for diagnosis. Critical illness myopathy (CIM) affects ICU bed-bound individuals who suffer muscle mass loss due to the loss of myosin (Rodriguez et al. 2022). Individuals with CIM had their UTF values monitored which demonstrated that there may be a correlation between elevated UTF values and muscle weakness (Nakano et al. 2021a, b), though this link is still tentative until more extensive studies can be conducted. The relationship between UTF levels and idiopathic inflammatory myopathy (IIM) have been explored as well due to its relation to muscle damage. They note that individuals with IIM have significantly higher UTF values compared to healthy controls, and those with skeletal muscle damage from IIM have even higher UTF values (Sun et al. 2023). This study also found that muscle enzymes like serum CK are positively correlated with UTF values and that scales for assessing skeletal muscle disease were also positively correlated with UTF values. Other conditions have the symptomology of elevated UTF values like non-alcoholic fatty liver disease (Oshida et al. 2019) and cardiomyopathy (Yoshihisa et al. 2018a, b).

Cardiac issues and muscle damage

As mentioned in the previous segment, cardiomyopathy increases UTF values with one study claiming that UTF values were additionally linked to cardiac and noncardiac related mortality in cardiomyopathy patients due to the muscle fiber damage associated with the disease (Yoshihisa et al. 2018a, b). Additionally, there is a use for UTF values in heart muscle research, such as examining a myocardial infarction. Myocardial infarction can have a 5–30% mortality rate, depending on patient conditions (Ojha and Dhamoon 2025), so determining an accurate method of mortality prediction is necessary. While this article found no statistical difference between individuals’ UTF values when they suffered an acute myocardial infarction (AMI) but were admitted within three hours and non-AMI controls, they found that AMI patients admitted after 3 h had significantly higher UTF values (Arase et al. 2024). To summarize, this study found that significantly more muscle damage was occurring after experiencing prolonged (> 3 h) AMI without medical intervention.

It has been proposed that UTF values could be used in characterizing the amount of proteolysis that occurred due to lack of oxygenated tissues which is critical to creating a prognosis. Another recent study highlighted UTF values in post-cardiac surgery patients, comparing the values of patients who underwent on-pump beating coronary artery bypass graft (CABG), off-pump CABG, and open-heart surgery. The findings indicated that all individuals displayed elevated UTF and no significant difference was detected between on- and off-pump CABG (Tanihata et al. 2019). While this study is specifically interesting because it implies that UTF values could be useful for post-operative myocardial damage analysis, it lacks further detail which would support their claim. Comparing operations with a control group in mice or rats, as done in their previous paper (Tanihata and Minamisawa 2023), would be valuable. At present, the paper makes some interesting speculations, but without any evidence to verify that the act of cutting through muscle tissue to install the pump was not the cause for the spike in UTF values, they should not be used conclusively to verify myocardial damage.

Real-life medical applications

UTF values have been associated with the severity of strokes, 105 patients were involved in a study that found that UTF values elevated sharply immediately after the onset of the stroke. However, later measurements on days 1 and 3 found that there were weaker correlations between UTF values and the impact of the stroke (Ishihara et al. 2021). The correlation between stroke severity and UTF levels requires further research as strokes are not known to cause muscle damage but rather a change to muscle function due to neural oxygen deprivation (Qi et al. 2023).

While strokes have been observed on a large scale in the previously described study, there is at least one case study including UTF values in a clinical setting. The case study on a 60 year old man presented to the ICU with acute respiratory distress syndrome due to influenza, and during his stay they used cannulation to oxygenate his tissues (Nakanishi et al. 2020). UTF values were used in conjunction with blood urea nitrogen levels to indicate severity of muscle catabolism, and following the cannulation both markers were elevated (Nakanishi et al. 2020). Given the uncertain correlation between muscle atrophy and UTF values, it is possible that the elevation stemmed from muscle atrophy, although it is important not to discount the potential muscle damage sustained from the trauma of the influenza infection, intubation, and cannulation.

Cancer and sarcopenia

Sarcopenia is the loss of muscle mass and function over time, typically brought up with regards to aging, but it is also a serious problem for cancer patients. As such, it’s been considered that UTF values should be used to evaluate sarcopenia alongside cancers. One study found that sarcopenia, the natural loss of muscle with age, had strong positive UTF value correlations while other indicators of muscle mass like BMI, albumin, or SMI had strong negative correlations (Miyoshi et al. 2020). However, there were no correlations to be made regarding UTF values and individuals with hepatobiliary-pancreatic or GI cancers (Miyoshi et al. 2020). Furthermore, sarcopenia was examined in 2024 in its manifestation in type II diabetics. This study found that there was a significant elevation in type II diabetic UTF values compared to that of the control samples and that these UTF values had strong negative correlations with muscle strength and performance, but this correlation could not be seen in the control group (Takiguchi et al. 2024).

Evidence has been provided which indicates that UTF values on post-operation day 1 may be predictive for long term muscle loss. The study uses 34 patients going in for gastroenterological cancer surgery. UTF values were collected before the surgery and for 6 months following it, and they found that the highest and most variable values were collected on day 1 following the surgery, and that it correlated with values like BMI, serum LDH, operative time, and intraoperative blood loss (Kyomen et al. 2025). UTF values appear to be indicative of the muscle stress induced by surgery and long-term muscle atrophy (Kyomen et al. 2025). Surgery is a traumatic event for the body and requires some level of tissue damage, so this is to be expected; however, the notion of using UTF values to assess and quantify that stress is a novel concept which may show some promise with further study.

Conclusions

UTF values have been a unique subject of research over the past decade since their first appearance in the Rouillon paper in 2014. During this time, they have been well established as elevated biomarkers in dystrophy patients and, with some more research, may become an effective method for diagnosing young children and infants with these diseases. UTF has also been well established in the athletic research field, demonstrating elevation in EIMD and athletic exertion. Despite there being inconclusive evidence on UTF being relevant to muscle atrophy, these values are being applied clinically to determine the extent of muscle loss in patients. UTF values still need research to confirm their value in some fields of research and medicine, but it should be noted that it is already providing value to research and a noninvasive method for evaluating muscle health.

Abbreviations

UTF

Urinary titin N-terminal fragment

ELISA

Enzyme Linked Immunosorbent Assay

HRP

Horse Radish Peroxidase

Cr

Creatinine

DMD

Duchenne Muscular Dystrophy

BMD

Becker muscular dystrophy (BMD)

LGMDR1

Limb-girdle muscular dystrophy

FMD

Fukuyama congenital muscular dystrophy

DM1

Myotonic dystrophy 1

CK

Creatine Kinase

ICU

Intensive Care Unit

EIMD

Exercise Induced Muscle Damage

RBE

Repeated Bout Effect

HMB

beta-hydroxy-beta-methyl butyrate

MSITC

6-(Methylsulfinyl)hexyl Isothiocyanate

CIM

Critical Illness Myopathy

IIM

Idiopathic Inflammatory Myopathy

MMP

Matrix Metalloproteinase

CABG

Coronary Artery Bypass Graft

AMI

Acute Myocardial Infarction

BMI

Body Mass Index

LDH

Lactate Dehydrogenase

Author contributions

NM did the literature review and drafted the initial manuscript. NM and MG worked together to revise the manuscript. All authors read and approved the final manuscript.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Competing interests

The authors declare no competing interests.