［Soft drinks & Health science］
L-citrulline supplementation is associated with improvements in vascular endothelial function and subjective symptoms, including shoulder stiffness and lower back pain, in middle-aged and older adults with high-normal blood pressure
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May 14, 2026
Kirin Holdings Company, Limited
TOKYO and MATSUYAMA, MAY 14, 2026 – Kirin Holdings Company, Limited (Kirin Holdings) and Matsuyama University conducted a clinical trial focusing on vascular aging in middle-aged and older adults to evaluate the effects of L-citrulline*1 intake on vascular function.
This study showed that L-citrulline intake was associated with improvements in vascular endothelial function and in related subjective symptoms, such as shoulder stiffness and lower back pain, in healthy middle-aged and older adults with high-normal blood pressure*2, as defined at the time of the study.
The results of this study will be presented at the 80th Annual Meeting of the Japan Society of Nutrition and Food Science*3, to be held from May 15 to May 17, 2026, and have been accepted for publication in the international scientific journal Nutrition Research.*4
*1 An amino acid found in abundance in plants of the Cucurbitaceae family, has been reported to support blood flow and help maintain vascular flexibility.
*2 Blood pressure measured in a clinical setting at 130–139 mmHg/85–89 mmHg; while not meeting the criteria for hypertension (≥140/90 mmHg), it is considered a stage associated with an increased risk of future hypertension and cardiovascular disease, for which lifestyle modification is recommended.
The stratification criteria in this study were based on the Japanese Society of Hypertension guidelines in effect at the start of the study; at that time, this blood pressure range was referred to as “high-normal blood pressure.” Following the 2025 revision of the guidelines, the terminology has been updated, but this category remains distinct from prehypertension.
*3 80th Annual Meeting of the Japan Society of Nutrition and Food Science (https://www2.aeplan.co.jp/jsnfs2026/)
*4 Vascular effects of L-citrulline supplementation in healthy adults are largely influenced by the prehypertensive range of blood pressure: A double-blind, randomized, placebo-controlled, parallel-group study - ScienceDirect（https://www.sciencedirect.com/science/article/pii/S0271531726000485）
As the population continues to age rapidly, increasing attention is focused on extending healthy life expectancy and improving quality of life (QOL).
Aging is not due to the deterioration of a single part of the body, but rather reflects the gradual decline of multiple physiological functions. Therefore, it is important to mitigate the risk of decline in these physiological functions.
As has been noted, “individuals are only as old as their arteries”*5, maintaining vascular function is linked not only to cardiovascular health but also to the maintenance of overall health, including cognitive function, kidney function, motor function, and even mood.
*5 Sir William Osler (1849–1919)
Against this backdrop, we focused on vascular aging, a factor closely linked to extending healthy life expectancy, and conducted a clinical trial to evaluate the effects of L-citrulline, a compound Kirin has been researching for many years, on vascular endothelial function and subjective symptoms associated with impaired vascular function.
These findings suggest that L-citrulline intake may be associated with improvements in vascular endothelial function and subjective symptoms associated with impaired vascular function, such as shoulder stiffness and lower back pain, in healthy middle-aged and older adults with high-normal blood pressure.
These findings provide fundamental insights for the further advancement of research on vascular aging based on vascular function.
Research Findings (Summary)
Among the 66 healthy adult men and women aged 45 to 70 who participated in the study, those with high-normal blood pressure at the start of the study showed significantly greater FMD, an indicator of vascular endothelial function, than the placebo group (Figure 1).
Similarly, among participants with high-normal blood pressure, improvements in subjective symptoms such as lower back pain and shoulder stiffness were observed in the group that consumed L-citrulline (Figure 2).
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Figure 1. Changes in vascular endothelial function following L-citrulline supplementation among middle-aged and older adults with high-normal blood pressure
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Figure 2. Changes in subjective symptoms of lower back pain and stiff shoulders following L-citrulline supplementation (change from baseline)
Implications
The study suggested that continuous intake of L-citrulline may be associated with improvements in vascular function and specific subjective symptoms, including lower back pain and shoulder stiffness, in healthy middle-aged and older adults with high-normal blood pressure.
Future Outlook
Moving forward, we aim to contribute to the extension of healthy life expectancy by further advancing research on vascular function and healthy aging, thereby helping to address health-related challenges.
About Kirin Holdings
Kirin Holdings Company, Limited is a global company operating across three core business domains spanning Alcoholic Beverages, Non-alcoholic Beverages & Health Science, and Pharmaceuticals. The company traces its roots to Japan Brewery, established in 1885, which later became Kirin Brewery in 1907. Since then, Kirin has expanded its business operations by leveraging fermentation and biotechnology as core strengths. The company entered the pharmaceutical field in the 1980s, which has since grown into a global business. In 2007, the company transitioned to a pure holding company structure as Kirin Holdings, and it is now strengthening its Non-alcoholic Beverages & Health Science domain.
Under its long-term vision “Innovate2035!”, the Kirin Group is focused on creating value that encourage behavioral change among consumers and patients, creating new lifestyle habits in the areas of food and health. With a unique business portfolio spanning Alcoholic Beverages, Non-alcoholic Beverages & Health Science, and Pharmaceuticals, the Group will further expand group-wide initiatives that support both mental and physical well-being.
The Kirin Group will continue to advance innovation through the combined strength of its people and technology, creating both social and economic value as a global leader in CSV*, while pursuing sustainable, long-term growth in corporate value.
*Creating Shared Value: combined added value for consumers as well as for society at large.
Vascular Effects of L-Citrulline Supplementation in Healthy Adults
Background and Objectives
It is known that impaired vascular function increases the risk of various systemic health disorders. Nitric oxide (NO)*, produced by the vascular endothelium, plays a crucial role in vascular relaxation and the prevention of atherosclerosis. Previous reports have demonstrated the effects of L-citrulline supplementation, a substrate for nitric oxide synthase, on vascular function. However, many of these reports have focused on studies involving patients with conditions such as angina or studies using relatively high doses of L-citrulline. Furthermore, since blood pressure exerts a pressure load on the arterial wall and affects vascular endothelial function, it was hypothesized that blood pressure status could be a key determinant in assessing the effects of L-citrulline. Therefore, this study aimed to evaluate the effects of low-dose L-citrulline supplementation on vascular function in healthy adults, with a focus on individuals with high-normal blood pressure.
* A molecule involved in vasodilation and the maintenance of blood flow
Research Methods
This study was conducted as a randomized, double-blind, placebo-controlled, parallel-group trial. The study included 66 healthy adult men and women aged 45 to 70 years with reduced vascular function. Participants were assigned to receive either L-citrulline supplementation (3,000 mg/day) or a placebo (containing no L-citrulline) for 12 weeks, and evaluations were conducted before the start of intake, at week 6, and at week 12. The outcomes included flow-mediated dilation (FMD), an indicator of vascular endothelial function, and serum 3-nitrotyrosine levels, a factor contributing to atherosclerosis. In addition, the severity of subjective symptoms of lower back pain and stiff shoulders was assessed using the Visual Analogue Scale (VAS), in which participants marked their current condition on a 10-cm line, with the left end representing “none at all” and the right end representing “very severe,” and the distance from the left end was quantified.
Research Results
In participants with high-normal blood pressure prior to the start of supplementation, 12 weeks of L-citrulline supplementation showed significantly greater FMD, an indicator of vascular endothelial function, than the placebo group (Figure 1).
Similarly, in participants with high-normal blood pressure prior to the start of supplementation, changes in subjective symptoms such as lower back pain and stiff shoulders were significantly greater in the L-citrulline group than in the placebo group (Figure 2).
Furthermore, changes in serum 3-nitrotyrosine levels, a factor contributing to atherosclerosis, were also significantly greater in the L-citrulline group than in the placebo group (Figure 3).
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Figure 1. Changes in vascular endothelial function following L-citrulline supplementation among middle-aged and older adults with high-normal blood pressure
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Figure 2. Changes in subjective symptoms of lower back pain and stiff shoulders following L-citrulline supplementation (change from baseline)
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Figure 3. Changes in serum 3-nitrotyrosine levels following L-citrulline supplementation (change from baseline) in participants with high-normal blood pressure
GALLERY
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Figure 1. Changes in vascular endothelial function following L-citrulline supplementation among middle-aged and older adults with high-normal blood pressure
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Figure 2. Changes in subjective symptoms of lower back pain and stiff shoulders following L-citrulline supplementation (change from baseline)
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Figure 3. Changes in serum 3-nitrotyrosine levels following L-citrulline supplementation (change from baseline) in participants with high-normal blood pressure