Article Information
Corresponding author : Vandana Garg

Article Type : Research & Retrospective Cross-Sectional Study

Volume : 6

Issue : 2

Received Date : 10 Jan ,2025


Accepted Date : 29 Jan ,2025

Published Date : 06 Feb ,2025


DOI : https://doi.org/10.38207/JCMPHR/2025/FEB06020108
Citation & Copyright
Citation: Garg V, Gadzhieva-Moore A, Wong AY, Lin J, Tan SSL (2025) Effectiveness of Undenatured Collagen Type II (UC-II) On Joint Mobility And Endurance: A Retrospective Cross-Sectional Study. J Comm Med and Pub Health Rep 6(02): https://doi.org/10.38207/JCMPHR/20

Copyright: © 2025 Vandana Garg. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
  Effectiveness of Undenatured Collagen Type II (UC-II) On Joint Mobility And Endurance: A Retrospective Cross-Sectional Study

Vandana Garg1*, Aida Gadzhieva-Moore2, An Yi Wong3, Joseph Lin4, Sheryl S. L. Tan5

1Haleon, GlaxoSmithKline Consumer Healthcare Pte Ltd, 23 Rochester Park, Singapore 139234. ORCID: https://orcid.org/0000-0001-8836-6928

2IQVIA Solutions Asia Pte Ltd, 79 Anson Road, Singapore 079906. ORCID: https://orcid.org/0009-0008-2757-6233

3Haleon, GlaxoSmithKline Consumer Healthcare Pte Ltd, 23 Rochester Park, Singapore 139234. ORCID: https://orcid.org/0009-0005-2011-9425 4Haleon UK Services Limited Taiwan Branch, 24F, No.66, Sec. 1 Zhongxiao W. Rd. Taipei 100507 Taiwan. ORCID: https://orcid.org/0009-0005- 5959-707X

5Haleon, GlaxoSmithKline Consumer Healthcare Pte Ltd, 23 Rochester Park, Singapore 139234. ORCID: https://orcid.org/0000-0002-7485-7037

*Corresponding Author: Vandana Garg, Haleon, GlaxoSmithKline Consumer Healthcare Pte Ltd, 23 Rochester Park, Singapore 139234. ORCID: https://orcid.org/0000-0001-8836-6928.

Abstract
Objectives:
This study aimed to examine the impact of joint symptoms on daily mobility and validate the perceived effectiveness of undenatured collagen type II's (Caltrate® UC-II) regular intake on improving joint mobility in healthy individuals experiencing joint symptoms.

Methods
A 2-phase retrospective cross-sectional study was conducted using self-administered online questionnaires. Phase 1 (n=111) included individuals aged 35 to 60 experiencing joint symptoms with no history of osteoarthritis or recent bone fracture to assess the impact of joint symptoms, specifically identifying areas which were most affected by joint conditions. Phase 2 (n=400) focused on regular users of Caltrate® UC-II's who consumed the product at least three times a week in the past three months prior to recruitment, while also meeting the same criteria as set in phase 1, to evaluate the perceived effectiveness of Caltrate UC-II on those specific areas identified in Phase 1. Participants who took part in phase 1 were not eligible to participate in phase 2. Continuous variables were summarized using mean and standard deviation (SD), while categorical variables were presented using frequency and proportion. Chi-square tests were used to compare categorical variables between groups, while Student's t-tests were applied for continuous variables. Statistical significance was determined at the 5% level (p < 0.05). All data analyses were conducted using IBM SPSS Statistics software, version 28.0.

Results:
Phase 1 has shown that joint symptoms significantly impact daily activities, with most respondents experiencing challenges with posture change (57.7%), climbing stairs (49.5%), squatting (40.5%), bending (30.6%), running (24.3%), and hiking (23.4%). Improvements in these activities was the most important benefit expected by respondents (62.2%) from supplements such as UC-II. In Phase 2, respondents reported a positive impact on daily activities after taking UC-II for 90 days, including more comfortable sitting up and down or changing posture (85.5%); climbing more stairs with less discomfort (84.5%), squatting with less discomfort (84.8%), more comfortable bending (87.8%); running longer distances with less discomfort (82.9%), improvement in the duration, discomfort, and speed while walking (84.5%). Overall, up to 90% of respondents experienced perceived improvements in all 6 daily mobility activities evaluated. Corresponding to these improvements, up to 86.3% reported positive emotional impact and improved quality of life (QoL).

Conclusion:
Our study findings complemented the existing science of UC-II and demonstrated how regular UC-II intake relieves joint symptoms and improves daily mobility.

Keywords: joint symptoms, quality of life, real-world evidence, supplements

Introduction
According to the Global Burden of Disease (GBD) 2019 analysis, around 1.71 billion individuals worldwide are affected by musculoskeletal conditions, including joint disorders (such as osteoarthritis and rheumatoid arthritis) and low back pain.[1] Consequently, musculoskeletal conditions are recognized as substantial contributors to global disability, accounting for approximately 149 million years lived with disability (YLDs), constituting 17% of all YLDs worldwide. This burden was expected to escalate due to the aging and expanding world population.[1] These conditions, impacting joints, bones, muscles, and supporting structures in limbs, neck, and back, often manifested as pain, accompanied by body aches, malaise, and stiffness in affected patients. [2,3]

Joint pain is considered one of the most common types of chronic pain,[4] and among the most affected joints are the knee joints. [5-7] It is also the primary cause of joint discomfort.[4,8] For instance, an 8-year longitudinal cohort study from the Osteoarthritis Initiative (OAI), consisting of 3,053 individuals, reported mild knee pain in at least 67 %.[9] A cross-sectional study conducted on 2,233 adults aged 40 years and older in Germany found that 75% of respondents had experienced joint pain in the current 1-month period, and around one- third reported knee pain.[10] In comparison, the prevalence of knee pain among the Asian population was in the range of 11% to 56% in China,[11,12] 21% to 33% in Malaysia, [7,13] 21% to 23% in Korea [14,15] in adults. Available prevalence data from worldwide studies therefore suggest the possibility of geographical locations in joint pain prevalence.

Several components of the musculoskeletal system play a crucial role in maintaining joint health. With age, bones and muscles gradually weaken over time due to a decline in both bone and muscle mass, as well as power.[16] Additionally, tendons and ligaments become less elastic over time, resulting in reduced flexibility and restricted joint movement.[17] These age-related changes in connective and muscle tissues are linked to a decreased maintenance of tissue homeostasis due to cell senescence and alterations in circulating factors among other cellular changes.[16] Additionally, the cumulative impact of repeated joint use over one's lifetime can gradually wear down the cushioning cartilage between joints, contributing to joint discomfort.[17] Several studies report that a noticeable decline in mobility becomes evident at 60 years of age, although signs of reduced mobility can be detected as early as 20 years of age when more challenging mobility tasks were performed.[18] Similarly, engaging in certain sports poses a risk factor for developing joint.[19] This irony arises as various guidelines advocate for exercise to manage age-related changes to joint health.[17,20] However, vigorous physical activity increases the likelihood of sustaining joint injuries. Sports such as wrestling and powerlifting entail excessive loading of joints, while activities like baseball and ice hockey involve high intensity joint impact, thereby elevating the risk of joint injury.[19] Common symptoms of joint discomfort include stiffness and a restricted range of movement around the affected joint.[19] These impede daily physical activities and jeopardize the individual's quality of life.

Considering knee pain or general joint discomfort as a perceived impediment to daily physical activities, a common strategy to improve mobility and flexibility involves addressing and alleviating discomfort associated with joint movement. Viable and readily accessible approaches for joint protection may include exercise and dietary interventions,[21,22] along with the use of nutraceutical supplements.[23,24] Undenatured collagen stands out as one such dietary supplement that can be utilized in individuals experiencing activity-related joint discomfort, potentially reducing the progression of issues like limited mobility.

Undenatured collagen type II (UC-II) is a natural ingredient derived from chicken sternum, which contains a glycosylated, undenatured type II collagen.[25] It is believed that UC-II exerted its effect via a mechanism in the gastrointestinal tract known as oral tolerance, which is the immune system's ability to become tolerant or less responsive to specific antigens when they are introduced through the oral route.[26,27] UC-II appears to simulate the regulatory T cells (immune cells) in secreting anti-inflammatory cytokines and inducing articular cartilage repair.[28] Compared to other types of collagen, UC-II contains active epitopes—smaller antigenic segments with the potential to elicit an immune response.[25] In vivo studies demonstrated that UC-II enhanced the mechanical function of a compromised joint, prevented undue degradation of articular cartilage, and reduced circulating levels of inflammatory cytokines.[27, 29, 30] Randomized controlled trials (RCTs) demonstrated that daily small doses (10mg to 40mg) of UC-II ameliorated joint symptoms in the population suffering from osteoarthritis (OA).[25,31,32] In healthy individuals experiencing joint discomfort or pain, intake of UC-II enhanced joint symptoms.[26,33-35] Daily intake of 40mg of UC-II for 90 days resulted in improved knee range of motion and reduced pain following a step mill performance test.26 Similarly, healthy individuals with activity-related joint discomfort exhibited significant enhancements in joint mobility (daily step count) and reduced discomfort (subjective discomfort level after repetitive stepping up and down from a platform) after 24 weeks of daily UC-II consumption compared to a placebo group.[33]

Given the significant impact of joint discomfort on everyday mobility activities, as well as the strong show of evidence supporting the benefits of UC-II intake, our cross-sectional study seeks to further validate the real-world effectiveness of regular UC-II intake on mobility health amongst existing product users (Caltrate® UC-II) in Taiwan.

Material and methods
Study design
This was a two-phase cross-sectional study conducted in Taiwan using self-administered, structured online questionnaires. Phase 1 involved respondents who had experienced joint symptoms, focusing on the activities impacted by their joint symptoms and the benefits sought when choosing joint health supplements. Phase 2 involved respondents who regularly used Caltrate® UC-II (daily dose of one tablet contains UC-II 40 mg; Vitamin C 45 mg; Magnesium 52.5 mg; Zinc 7.5 mg; Copper 0.5 mg; Manganese 1.8 mg) to assess their perceived improvement in joint symptoms. There was no overlap in respondents in both phases.

Participants
In the Phase 1 study, eligible respondents were residents of Taiwan aged between 35 and 60. They were required to be self-declared individuals who had experienced joint discomfort, pain, or stiffness in the past 3 months and were open to health supplements or over-the- counter medication for joint relief. Exclusion criteria encompassed having been diagnosed with chronic illnesses such as osteoarthritis, fibromyalgia, gout, or lupus, as well as experiencing bone fractures or broken bones within the preceding 6 months. In Phase 2 of the study, respondents were recruited under the same eligibility criteria as in Phase 1, with the additional criteria that they had been using Caltrate® UC-II for joint relief at least three times a week in the past three months. Sample sizes were calculated using Cochran's (1977) formula. For Phase 1, a minimum required sample of 100 respondents was determined with a 10% margin of error, a standard deviation (SD) of 0.5, and a 95% confidence interval (CI); the final sample for analysis in Phase 1 included data collected from N=111 respondents. For Phase 2, a sample of 400 respondents was determined with a 5% margin of error, SD of 0.5, and a 95% CI; the final sample for analysis in Phase 2 included data collected from N=400 respondents.

Data collection and procedure
Respondents were recruited via an online consumer panel representative of the general population in Taiwan using an online link. The recruitment process also employed quota sampling, with adaptable quotas for age and gender closely monitored throughout. In both phases of the study, interested respondents who accessed the online link were first presented with an informed consent explaining the use of their data and a pre-screening questionnaire. Only those who met the inclusion criteria in the pre-screening questionnaire and aligned with age and gender quotas were invited to complete the remainder of the questionnaire.

Respondents in the Phase 1 study were asked to detail the daily activities impacted by their joint symptoms, their activity metrics performance (e.g., in daily steps, squatting, running performance and daily stairs count), and the key benefits they sought from joint health supplements. In Phase 2, respondents were asked about their perceived effectiveness and satisfaction with the use of Caltrate® UC- II in alleviating joint discomfort, pain, or stiffness and improvement in joint mobility and physical endurance. Respondents were also asked to provide the perceived quantitative changes in daily metric performance encompassing metrics such as daily steps count in walking, running frequency, distance, and duration per session, and squat counts, both before and after incorporating Caltrate® UC-II into their routine. For instance, the perceived quantitative changes in daily steps count for walking were captured by the question: "Thinking about the time before you started taking Caltrate® UC-II, how many steps did you use to walk on an average day? and after taking it for 90 days?" The questionnaire was constructed based on the analysis of a social media listening study involving approximately 6,000 spontaneous online conversations about joint health and mobility, sourced from various blogs, forums, and social networks.

Data analysis
The study endpoints for both phases remain unchanged during the study. In both study phases, only completed questionnaires were analyzed. Respondent characteristics and demographics were summarized using descriptive statistics. Continuous variables were summarized using mean and standard deviation (SD), while categorical variables were presented using frequency and proportion. When comparing between groups, the chi-square test was used for categorical variables. For continuous variables, a Student's t-test was used. The significance of differences between groups was assessed at a 5% significance level (p < 0.05). All data analysis was performed using IBM SPSS Statistics software, version 28.0.

Results
Demographic and joint treatment usage profile

The respondents' characteristics and health supplement usage in both phases were displayed in Table 1. In Phase 1 of the study, a total of 111 respondents completed the questionnaire. The respondents recruited were fairly representative in sex distribution with 48.6% being male and 51.4% female. The majority were between the ages of 40 to 49 years (49%). Approximately two-thirds (64.9%) of the respondents reported experiencing joint bruising, and slightly over one-third (37.8%) had joint sprains in the past 6 months. Additionally, approximately  two-thirds reported experiencing headaches in the past three months. Respondents had also reported treatment to alleviate their joint symptoms in the past three months, with the majority utilizing topical medications and health supplements (66.7% and 55.9%, respectively). Amongst those who had consumed health supplements to relieve their joint symptoms, the most commonly reported options were Glucosamine (65.2%) and type 2 collagen (UC-II) (46.4%). The distribution of type of glucosamine and UC-II consumed by participants are presented in Table 2.

Table 1: Demographics and respondents’ usage profile in both study phases

Characteristics

Phase 1 (N =111)

 

Phase 2 (N=400)

n

%

 

n

%

Gender

 

 

 

 

 

Male

54

48.6%

 

250

62.5%

Female

57

51.4%

 

150

37.5%

Age

 

 

 

 

 

Mean (SD)

44.9 (6.6)

 

46.6 (7.0)

35-39 years old

29

26.1%

 

80

20.0%

40-49 years old

54

48.6%

 

181

45.3%

50-60 years old

28

25.2%

 

139

34.8%

Monthly household income (NT$)

 

 

 

 

 

Mean (SD)

111,621.6 (29,062.3)

 

133,300.0 (38,035.9)

70,001 - 90,000

40

36.0%

 

42

10.5%

90,001 - 110,000

19

17.1%

 

71

17.8%

110,001 - 130,000

13

11.7%

 

106

26.5%

130,001 - 150,000

12

10.8%

 

101

25.3%

150,001 or above

27

24.3%

 

80

20.0%

Condition Experienceda

 

 

 

 

 

Joint stiffness/ pain/ discomfort

111

100.0%

 

400

100.0%

Headache

73

65.8%

 

145

36.3%

Sore throat

56

50.5%

 

146

36.5%

Stomach-ache

43

38.7%

 

128

32.0%

Atopic dermatitis/ eczema

54

48.6%

 

161

40.3%

Injuries (P6M)

 

 

 

 

 

Bruising

72

64.9%

 

90

22.5%

Joint sprain

42

37.8%

 

97

24.3%

Ligament trauma

9

8.1%

 

50

12.5%

Others

0

0.0%

 

244

61.0%

Joint treatment P3M

 

 

 

 

 

Oral prescription medications

24

21.6%

 

152

38.0%

Oral medications available without

prescription/ over-the-counter

19

17.1%

 

237

59.3%

Health supplements/ health food

62

55.9%

 

332

83.0%

Topical medications – creams, gels, rubs etc.

74

66.7%

 

174

43.5%

Natural remedies/ herbals/ TCM

34

30.6%

 

116

29.0%

Physiotherapy/ massage

55

49.5%

 

166

41.5%

TENS

11

9.9%

 

78

19.5%

Others

1

0.9%

 

0

0.0%

Nothing at all

11

9.9%

 

0

0.0%

Supplement used P3Mb

 

 

 

 

 

Undenatured Type II Collagen (UC-II)

32

46.4%

 

400

100.0%

Glucosamine

45

65.2%

 

177

44.3%

Caltrate® UC-II usage duration (months)***

 

 

 

 

 

Mean (SD)

-

 

6.1 (1.7)

3 months

-

-

 

44

11.0%

4 months

-

-

 

41

10.3%

5 months

-

-

 

87

21.8%

> 6 months

-

-

 

228

57.0%

Caltrate® UC-II usage frequency (weekly)b

 

 

 

 

 

Mean (SD)

-

 

5.1 (1.4)

3 times/week

-

-

 

65

16.3%

4-5 times/week

-

-

 

207

51.8%

Daily

-

-

 

128

32.0%

Abbreviations: -, Non-applicable; P6M, past 6 months; P3M, past 3 months; TENS, Transcutaneous Electrical Nerve Stimulation; TCM,

Traditional Chinese Medicine

aCondition experienced was assessed for the past 3 months at Phase 1 and for the past 12 months at Phase 2

bThe number of respondents assessed for supplement brand in Phase 1 is 69

cCaltrate® UC-II usage profile was assessed in Phase 2 study only.

Table 2: Type of joint treatment supplements taken by participants in phase 1

Type of joint treatment supplements

Phase 1 (n=69*)

n

%

Caltrate UCII

18

26.1%

Move Free UCII

13

18.8%

Viatril-S Glucosamine

27

39.1%

Suntory Glucosamine

24

34.8%

Kirkland Glucosamine

10

14.5%

BRANDS UCII

16

23.2%

Others

1

1.4%

None of the above

13

18.8%

*A subset of participants in phase 1 who indicated that they consumed ‘Oral medications available without prescription/ over-the-counter’ or ‘Health supplements/ health food’

Respondents in Phase 2 comprised 400 UC-II users, within the age of 40 to 49 years (45.3%). More than one-third of participants reported occurrences of atopic dermatitis (40.3%), sore throat (36.5%), and headaches (36.3%) over the past 12 months. In addition, a major proportion of respondents (61.0%) indicated experiencing nonspecific joint-related injuries, followed by joint sprains (24.3%) and bruises (22.5%) within the previous six months. Four in five respondents (83.0%) reported consuming joint health supplements as part of joint health treatment over the past three months, and 57% had been using UC-II for over 6 months, typically at a frequency of 5 times a week.

Effect of joint symptoms on daily activities and desired benefits from joint supplements
Respondents encountered difficulties in daily activities due to joint symptoms, with the most affected mobility aspects being posture change and climbing stairs (57.7% and 49.5%, respectively), followed by squatting (40.5%), bending (30.6%), running (24.3%), and hiking (23.4%) (Figure 1a). Consequently, the most important benefits that respondents sought in a joint health supplement included the improvement in the five daily mobility areas (Figure 1b). 62.2% of the respondents have rated "improves my mobility for the 5 most important daily activities -1 Climbing stairs 2 Running 3 Squatting 4 bending 5 walking" as their first or second priority when selecting a joint health supplement.

Figure 1a: Daily activities impacted by joint symptoms.

Figure 1b: Desired benefits from joint health supplements

Figure 1a&b. Daily activities impacted by joint symptoms and desired benefits from joint health supplements. (a) The aggregated percentages of daily activities most affected by joint symptoms reported by the respondents. (b)The aggregated percentages of the most important benefits that respondents sought for in a joint supplement. Data based on Phase 1 study (n = 111).

Perceived benefits in joint symptoms, mobility, and endurance following 90 days of UC-II consumption
In general, nine in ten respondents reported improvements in across all joint symptoms following their use of UC-II over the past 3 months, encompassing reduced joint discomfort (90.8%), decreased joint and knee joint stiffness (88.0% and 89.5%, respectively) as well as improvement in joint flexibility (90.3%) and range of motion (87.5%).

Additionally, 90% of UC-II users reported perceived improvement in the 6 most important daily mobility areas, including climbing stairs, walking, squatting, bending, running, and posture change. Specifically, over 90% of users observed a significant doubling in their daily walking steps to an average of 4,087 steps after UC-II intake (p < 0.001) (Table 3). Additionally, more than 80% of users reported enhancements in discomfort, duration, and walking speed (Table 3). Half of the respondents in Phase 1 reported significant limitations in climbing stairs due to joint symptoms, resulting in fewer than 5 flights of stairs being climbed daily. However, over 80% of UC-II users reported improved endurance and comfort when climbing stairs (Table 4). Regular UC-II users also noticed improvements in the duration, distance, and speed of running, with less discomfort (Table 4). Quantitatively, nine in ten users reported a significant increase in their running frequency to approximately five times per week, along with a two-fold increase in their average running distance and running time (p < 0.001) (Table 3). Moreover, users experienced reduced discomfort during squatting, with a significant two-fold increase in squatting frequency on average following UC-II usage (p< 0.001) (Table 3 and Table 4). Respondents also reported benefits in bending, providing increased comfort during daily activities and physical exercises such as yoga and stretching exercises (Table 4).

Table 3. Perceived quantitative changes in mobility benefits after taking Caltrate® UC-II

 

Mobility areas

Before taking Caltrate® UC-II; Mean (SD)

After taking Caltrate® UC-II; Mean (SD)

Mean Difference; Mean (SD)

 

p-value

Walking

 

 

 

 

Daily steps count

3,367.5

(2,320.1)

7,454.4 (2,594.1)

4,086.9 (2,472.7)

<0.001*

Running

 

 

 

 

Frequency/week

2.3 (1.8)

5.3 (3.4)

2.9 (2.2)

<0.001*

Distance (km) / session

1.8 (1.1)

4.0 (1.5)

2.3 (1.3)

<0.001*

Duration (min) / session

16.4 (8.4)

36.3 (12.1)

20.0 (12.6)

<0.001*

Squatting activities

 

 

 

 

Squat counts/ 30 seconds

9.3 (7.4)

18.1 (11.6)

9.3 (7.6)

<0.001*

 Abbreviations: SD, Standard deviation; km, kilometers; min, minutes
*Significant results

Table 4: Perceived benefits in 5 mobility areas (i.e., walking, climbing stairs, running, squatting, and bending) after 90 days of Caltrate® UC-II intake (N = 400)

Mobility Areas Attribute Statements

Percentage reported (%)

Agree

Neutral

Disagree

Walking

 

 

 

1

Since I started taking Caltrate® UC-II, my mobility can last longer

79.3%

19.3%

1.5%

2

I can walk 30 min or more without discomfort, after taking Caltrate® UC-II

for 90 days

80.0%

18.8%

1.3%

3

Since I started taking Caltrate® UC-II, I enjoy walking more

80.0%

17.5%

2.5%

4

After taking UC-II for 90 days, I can walk 7,000 steps a day or more

without discomfort

80.3%

17.5%

2.3%

5

I can walk longer distance after taking Caltrate® UC-II for 90 days

80.8%

16.5%

2.8%

6

I can walk longer distances without discomfort after taking Caltrate® UC-II

for 90 days

80.8%

16.3%

3.0%

7

I can walk for longer time after taking Caltrate® UC-II for 90 days

82.0%

16.5%

1.5%

8

I enjoy walking more often after taking Caltrate® UC-II for 90 days

83.8%

14.5%

1.8%

9

I have noticed improvement in the duration, discomfort, and speed while

walking since I started taking Caltrate® UC-II

84.5%

14.8%

0.8%

Climbing stairs

 

 

 

1

I can climb 10 flights of stairs with no discomfort after taking Caltrate®

UC-II for 90 days

82.0%

10.8%

3.0%

2

I can climb 5 flights of stairs with no discomfort after taking Caltrate® UC-

II for 90 days

82.5%

11.0%

1.8%

3

After taking Caltrate® UC-II for 90 days, I now choose to take the stairs

more often instead of elevator

83.8%

10.5%

2.5%

4

After taking Caltrate® UC-II for 90 days, I can comfortably climb stairs

84.0%

11.3%

2.3%

5

After taking Caltrate® UC-II for 90 days, I can climb more floors, with less

discomfort

84.5%

10.3%

1.8%

6

I can climb stairs with less discomfort after taking Caltrate® UC-II for 90

days

86.0%

8.3%

1.8%

Running

 

 

 

1

I can run longer distance after taking Caltrate® UC-II

78.1%

19.4%

2.6%

2

I can run comfortably after taking Caltrate® UC-II for 90 days

82.7%

15.6%

1.8%

3

Since I started taking Caltrate® UC-II, I enjoy running more

83.2%

14.5%

2.3%

4

I have noticed an improvement in the duration, discomfort, and speed while

running since I started taking Caltrate® UC-II

79.9%

18.1%

2.0%

5

I can run longer distances with less discomfort after taking Caltrate® UC-II

for 90 days

82.9%

15.6%

1.5%

6

I can run with my friends and family and don’t have the fear of getting left

behind after taking Caltrate® UC-II

79.1%

19.6%

1.3%

7

After taking Caltrate® UC-II for 90 days, I can run 2km or more a day with

less discomfort

79.9%

18.6%

1.5%

8

After taking Caltrate® UC-II for 90 days, I can run for a longer time with

less discomfort

78.8%

19.6%

1.5%

Squatting

 

 

 

1

I can squat longer after taking Caltrate® UC-II for 90 days

83.0%

13.3%

0.8%

2

I can do a greater number of squats with less discomfort, after taking

Caltrate® UC-II for 90 days

84.8%

11.5%

1.5%

3

I can squat comfortably after taking Caltrate® UC-II for 90 days

87.3%

9.8%

0.8%

4

After taking Caltrate® UC-II for 90 days, I can comfortably use / get on

and off the toilet

86.5%

10.8%

1.0%

5

After taking Caltrate® UC-II for 90 days, I can comfortably squat and lift

things off the floor

86.5%

10.3%

1.0%

6

After taking Caltrate® UC-II for 90 days, I can squat without discomfort

and get things from bottom shelves in supermarkets/ from refrigerators

88.3%

8.3%

0.5%

7

After taking Caltrate® UC-II for 90 days, I can squat without discomfort to

clean/ mop the floor

85.8%

11.3%

1.0%

8

After taking Caltrate® UC-II for 90 days, I can comfortably squat and feed

the pets

83.5%

11.5%

1.5%

9

After taking Caltrate® UC-II for 90 days, I can comfortably squat and tie

my shoelaces

86.8%

9.5%

1.0%

10

Standing up from a crouching/ squatting position is easier after taking

Caltrate® UC-II for 90 days

85.3%

11.3%

1.3%

  Bending      

1

After taking Caltrate® UC-II for 90 days, my bending movements are

smoother and more comfortable

87.8%

9.5%

0.5%

2

After taking Caltrate® UC-II for 90 days, I can bend comfortably to put on/

take off socks or shoes

86.8%

11.5%

0.8%

3

After taking Caltrate® UC-II for 90 days, I can bend comfortably and pick

up objects from the floor

85.8%

12.3%

0.5%

4

After taking Caltrate® UC-II for 90 days, I can bend comfortably and do

stretching exercise

86.3%

10.5%

0.8%

5

After taking Caltrate® UC-II for 90 days, I can bend comfortably and sit in

the car

88.5%

8.0%

0.5%

Perceptions and Satisfaction of Caltrate® UC-II
Approximately 90% of Caltrate® UC-II users appreciated the smaller tablet size and once-a-day intake regimen for its convenience (Figure 2). Corresponding to the improvements in joint symptoms with regular Caltrate® UC-II intake, users also reported enhanced QoL and lifestyle improvements. Over 80% of users reported a substantial positive emotional impact and improved QoL, as they are able to engage in increased physical activities and exercise, contributing to a healthier and more active lifestyle (Figure 2).

Overall, 95.8% of regular users were satisfied with Caltrate® UC-II to maintain their joint health, with over 90% of them trusting, planning to continue purchasing it, and willing to recommend it to others (Figure 3).

Figure 2: Lifestyle and quality of life (QoL) related perception and satisfaction among Caltrate® UC-II user. Data based on 400 respondents’ agreement (Phase 2) to the listed lifestyle and QoL statements. The aggregated score of respondents who selected ‘Somewhat Agree’ and ‘Completely Agree’ in a 5-point rating scale is presented.

Figure 3: Overall satisfaction with Caltrate® UC-II. Data based on 111 respondents’ agreement (Phase 1). The aggregated percentages of respondents’ satisfaction with Caltrate® UC-II are presented.

Discussion
This cross-sectional study conducted in Taiwan explored the impact of joint symptoms in daily mobility areas, the desired health benefits consumers are looking for in joint supplements and the potential benefits consumers experienced after consumption of a joint health ingredient – Type II undenatured collagen (UC-II). The study demonstrated that joint symptoms greatly affected different mobility areas, with posture changes such as standing up and sitting down as the most impacted area, followed by walking, climbing stairs, running, squatting, and bending. Respondents also valued joint supplements that could help improve in these six mobility areas. Regular users of UC-II (consumption of Caltrate® UC-II for more than 90 days) perceived positive changes in overall joint symptoms, mobility, as well as lifestyle and QoL-related benefits. This is corroborated by the findings of Lugo et al. [26] indicating that supplementation with 40mg of UC-II over a 90-day period enhanced joint mobility. In general, users reported high rates of satisfaction with Caltrate® UC-II, and thus, this confirmed the consumer acceptance of consuming Caltrate® UC-II to relieve their joint discomfort.

The results of the present study indicated that a substantial proportion, varying from two to five in every ten individuals within the general population in Taiwan with joint symptoms, encountered limitations in the five key mobility aspects: walking, climbing stairs, running, squatting, and bending. This finding is in line with existing literature where mobility limitations in daily activities are prominently associated with joint symptoms, encompassing pain, stiffness, and discomfort. [36,37] More importantly, these mobility limitations may eventually contribute to worsened mobility conditions and reduced quality of life. A cross-sectional study showed that decreased of physical activities with Rheumatoid Arthritis (RA) induced knee pain potentially speed age-related muscle that could eventually lead to loss of independence.[38]

Posture changes such as standing up and sitting down was also identified as the daily acitvitiy that was most impacted by joint symptoms, with over half of the respondents reporting challenges in standing up and/or sitting down due to joint symptoms.

The results of the perceived benefits of 90 days of regular consumption of UC-II on joint flexibility and mobility, reported by nearly 90% of the respondents in the present study, complement previous findings from RCTs conducted on healthy adults with no history of joint diseases. For instance, four to six months of UC-II supplementation improved knee flexibility on the range of motion extension and flexion in adults with activity-related joint discomfort aged < 65, compared to placebo control.[26,35] Schön, Knaub, Alt, Durkee, Saiyed and Juturu [35] further observed this improvement as early as 8 weeks (or 56 days). Another RCT that used daily step count to assess joint mobility, via a step counter, found that participants in the UC-II group took significantly more steps (increased by 217 steps) compared to the placebo group (decreased by 530 steps.[33] These findings could be attributed to the reduced joint discomfort rendering into increased mobility, where the same studies also found an increased time or more repetition before the onset of joint pain when subjected to intervention-controlled mobility tests (i.e., step mill test).[26,35] Therefore, the results of our study, where approximately 90% of respondents reported experiencing alleviation in joint discomfort and stiffness after 90 days regular use of UC-II, support existing published clinical findings. It further provided a real-world perspective to the use of UC-II on healthy adult populations.

Over 95% of consistent users of Caltrate® UC-II expressed satisfaction with their UC-II consumption. This satisfaction corresponded to the perceived positive impact on lifestyle changes and QoL following UC-II intake. Users reported increased confidence and comfort in daily activities, as well as a greater willingness to engage in an active lifestyle, including activities like yoga, running, and hiking. Previous studies have also shown that UC-II effectively enhanced joint comfort, subsequently improving the health-related QoL in OA patients.[31,39] Studies involving healthy adults with joint discomfort have also suggested a reduction in pain duration and recovery time within the UC-II group compared to the placebo group, potentially suggesting confidence of engaging in more physical movements and exercise in these populations.[26,33]

The primary strength of the current study was the investigation of real-world evidence, allowing insight into the perceived benefits of a product or intervention that has undergone thorough evaluation for safety and efficacy, emphasizing the relevance of this methodology. However, this approach resulted in a non-causal interpretation of the finding, and the study's outcomes necessitate cautious interpretation due to a few limitations. The study population predominantly comprised younger adults with an average age of 46, limiting generalizability to an older population, as observed in previous studies on healthy populations with joint symptoms.[26,33,35] Older adults often report a higher incidence of knee pain,[40] and a study suggested that the benefits of UC-II might extend more effectively to this demographic (> 50 years).[34] Furthermore, the Phase 2 study exclusively recruited respondents who were regular users of Caltrate® UC-II (> 90 days) in Taiwan, limiting the generalizability of the results to non-frequent users and individuals outside Taiwan. The recruitment method through an online survey panel, with the requirement of digital device access, may have excluded individuals with limited technology access. Additionally, findings related to Caltrate® UC-II consumption and perceived benefits on joint symptoms and daily mobility areas could be subject to self-reported bias, including recall bias and social desirability.[41] Lastly, there is an absence of a control group in this study, which could provide a more robust comparison to evaluate the effectiveness of Caltrate® UC-II. We encourage future studies to incorporate a control group to further validate and enhance the findings of this research.

Conclusion
This 2-phase cross-sectional study demonstrated the substantial impact of joint symptoms on diverse mobility aspects as well as the perceived benefits and improvements in joint symptoms, mobility, and overall QoL following regular Caltrate® UC-II consumption. Our findings contribute to a better understanding of real-world benefits with regular intake of Caltrate® UC-II, amongst the healthy population in Taiwan experiencing joint symptoms. The high satisfaction rates among users confirmed the acceptance of consuming Caltrate® UC-II to optimize their joint and mobility health.

Acknowledgments
The authors would like to thank Shi Mun Yee for the support in data analysis and report writing; Christler John Real for the support in data processing and analysis; and Freda Jia Xin Jong for the support in report writing.

Authors’ contributions
All authors contributed to the conception of the work and interpreted the data for the work. They revised the work and approved the final version. They agreed to take responsibility for the accuracy or integrity of the work as a whole. They had complete access to the study data that supports the publication. All authors have read and agreed to the published version of the manuscript.

Disclosure Statement
IQVIA has received research funding from GlaxoSmithKline Consumer Healthcare Pte Ltd. The authors are employees of IQVIA and GlaxoSmithKline Consumer Healthcare Pte Ltd. The authors report no other potential conflicts of interest.

Funding
This research was funded by GlaxoSmithKline Consumer Healthcare Pte Ltd.

Ethics approval and informed consent
This was an observational study. No ethical approval and clinical trial registration was required due to the non-interventional nature of the study. This study was conducted according to the guidelines laid down in the Declaration of Helsinki. Informed consent was obtained from all individual respondents before their inclusion in the study. No personal identifiable information of the participants was collected in the course of this study.

About the authors
Vandana Garg is the Director, Medical & Scientific Affairs (Southeast Asia and Taiwan) at Haleon. She has worked in the healthcare industry for more than 15 years with a vast experience in medical affairs across multiple markets and therapeutic areas, in both pharmaceuticals & consumer healthcare. Vandana is passionate about bringing more science backed healthcare innovations to consumers and in her current role at Haleon, she provides medical leadership on innovation and evidence generation for brands such as Centrum and Caltrate.

Aida Gadzhieva-Moore is an Associate Principal at IQVIA Consumer Health in Singapore, where she leads real-world evidence and claim substantiation practice. She holds a BSc in Economics and Management from the London School of Economics and Political Science, UK. With over 15 years of experience in research and analytics across healthcare and other categories, her work focuses on establishing best practices for real-world data generation within Consumer Health industry.

An Yi Wong holds a diploma in Biomedical Science from Ngee Ann Polytechnic and is currently pursuing her Bachelor’s degree with Honours in Biomedical Science and Biobusiness from Nanyang Technological University. An Yi has experience conducting research at both academic and research institutions. An Yi is currently a Medical and Scientific Affairs Intern at Haleon.

Joseph Lin is the Medical and Scientific Manager in Haleon, with has medical and regulatory affairs experience in healthcare and pharmaceutical industries over 15 years, and currently support Southeast Asia and Taiwan business unit.

Sheryl S. L. Tan holds a Ph.D. from the Yong Loo Lin School of Medicine, National University of Singapore, and did her post- doctorate fellowship in Lung Diseases. She has 10 years of research experience in pre-clinical drug development, in the fields of immunology, cancer and respiratory. Sheryl is currently the Head of Medical & Scientific Affairs for Haleon Wider Asia, where she leads real world evidence generation and research partnerships.

Data Availability Statement
The original contributions presented in this study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author(s).

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