hydrogen rich water 수소수의 치매치료 효과 논문

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hydrogen rich water 수소수의 치매치료 효과 논문

The effects of 6-month hydrogen-rich water intake on molecular and phenotypic biomarkers of aging in older adults aged 70 years and over: A randomized controlled pilot trial

Author links open overlay panelDragana Zanini a, Nikola Todorovic a, Darinka Korovljev a, Valdemar Stajer a, Jelena Ostojic b, Jelena Purac c, Danijela Kojic c, Elvira Vukasinovic c, Srdjana Djordjievski c, Miron Sopic d, Azra Guzonjic d, Ana Ninic d, Sanja Erceg d, Sergej M. Ostojic a

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https://doi.org/10.1016/j.exger.2021.111574Get rights and content

Abstract

In this randomized controlled pilot trial, we investigated the effects of a 6-month intake of hydrogen-rich water (HRW) on several molecular and phenotypic biomarkers of aging in older adults aged 70 years and over. Forty older adults (20 women) were randomly allocated in a parallel-group design to receive 0.5 L per day of HRW (15 ppm of hydrogen) or control drink (0 ppm of hydrogen) during a 6-month intervention period. The biomarkers assessed at baseline and 6-month follow up were molecular markers in the blood (DNA and chromosomes, nutrient sensing, protein, and lipid metabolism, oxidative stress and mitochondria, cell senescence, inflammation), brain metabolism, cognitive functioning, physical function and body composition, resting blood pressure, facial skin features, sleep outcomes, and health-related quality of life. The mean age, weight, and height of study participants were 76.0 ± 5.6 years, 78.2 ± 16.1 kg, height 167.5 ± 11.5 cm, respectively. A significant treatment vs. time interaction was found for telomere length (P = 0.049), with the length increased after HRW intervention (from 0.99 ± 0.15 at baseline to 1.02 ± 0.26 at follow up) and decreased after drinking control water (from 0.92 ± 0.27 to 0.79 ± 0.15). A marker of DNA methylation (Tet methylcytosine dioxygenase 2, TET2) expression‎ at 6-month follow-up increased in both groups, yet the degree of elevation was significantly higher in HRW (from 0.81 ± 0.52 at baseline to 1.62 ± 0.66 at follow up) comparing to the control water (from 1.13 ± 0.82 to 1.76 ± 0.87) (P = 0.040). A strong trend for treatment vs. time interaction was found for a degree of DNA methylation (P = 0.166), with the methylation increased in the HRW group (from 120.6 ± 39.8 ng at baseline to 126.6 ± 33.8 ng at follow up) and decreased after taking control water (from 133.6 ± 52.9 ng to 121.2 ± 38.4 ng). HRW was superior to control water to increase brain choline and NAA levels in the left frontal grey matter, brain creatine at the right parietal white matter, and brain NAA at the right parietal mesial grey matter (P < 0.05). No significant differences were found between interventions for other outcomes (P > 0.05), except for a significantly improved chair stand performance after HRW intervention compared to the control water (P = 0.01). Owing to pleiotropic mechanisms of hydrogen action, this simple biomedical gas could be recognized as a possible anti-aging agent that tackles several hallmarks of aging, including loss of function and telomere length shortening. The study was registered at ClinicalTrials.gov (NCT04430803).

이 무작위 대조 파일럿 시험에서는 70세 이상 노인의 노화를 나타내는 여러 분자 및 표현형 바이오마커에 대한 6개월간의 수소 함유 물(HRW) 섭취의 효과를 조사했습니다. 40명의 노인(여성 20명)을 무작위로 배정하여 6개월의 중재 기간 동안 하루 0.5L의 HRW(수소 15ppm) 또는 대조 음료(수소 0ppm)를 마시게 하는 평행군 설계로 진행했습니다. 

연구 시작 시점과 6개월 추적 관찰 시 평가한 바이오마커는 혈액 내 분자 마커(DNA 및 염색체, 영양소 감지, 단백질 및 지질 대사, 산화 스트레스 및 미토콘드리아, 세포 노화, 염증), 뇌 대사, 인지 기능, 신체 기능 및 체성분, 안정 시 혈압, 얼굴 피부 특징, 수면 결과, 건강 관련 삶의 질 등이었습니다. 연구 참가자의 평균 연령, 체중, 키는 각각 76.0±5.6세, 78.2±16.1kg, 167.5±11.5cm였습니다. 텔로미어 길이(P = 0.049)에 대해 치료와 시간 간 유의한 상호작용이 발견되었으며, HRW 개입 후 길이가 증가(기준치 0.99 ± 0.15에서 추적 관찰 시 1.02 ± 0.26)하고 대조군 물을 마신 후 감소(0.92 ± 0.27에서 0.79 ± 0.15)했습니다. 6개월 추적 관찰 시 DNA 메틸화(Tet 메틸시토신 디옥시게나제 2, TET2) 발현의 마커는 두 그룹 모두에서 증가했지만, 그 증가 정도는 대조군(1.13 ± 0.82에서 1.76 ± 0.87)에 비해 HRW(기준치 0.81 ± 0.52에서 추적 관찰 시 1.62 ± 0.66)에서 유의하게 더 높았습니다(P = 0.040). DNA 메틸화 정도(P = 0.166)에서 치료 대 시간 상호 작용에 대한 강력한 경향이 발견되었으며, HRW 그룹에서는 메틸화가 증가했고(기준치 120.6 ± 39.8ng에서 추적 관찰 시 126.6 ± 33.8ng) 대조군 섭취 후 감소했습니다(133.6 ± 52.9ng에서 121.2 ± 38.4ng으로). HRW는 대조군 물보다 좌측 전두엽 회백질, 우측 두정엽 백질, 우측 두정엽 내측 회백질에서 뇌 콜린과 NAA 수치를 증가시키는 데 더 효과적이었습니다(P <0.05). 대조군에 비해 HRW 개입 후 의자 스탠드 성능이 유의미하게 개선된 것을 제외하고 다른 결과에서는 개입 간에 유의미한 차이가 발견되지 않았습니다(P > 0.05)(P = 0.01). 이 간단한 생체 의료용 가스는 플라이오트로픽 작용 메커니즘으로 인해 기능 상실 및 텔로미어 길이 단축을 포함한 노화의 여러 특징을 해결하는 노화 방지제로 인식될 수 있습니다. 이 연구는 ClinicalTrials.gov(NCT04430803)에 등록되었습니다.

Introduction

The increase in the number of older adults across developed countries is unprecedented. In 2016, approximately 50 million U.S. adults were aged 65 years or older, representing 15% of the population. That number is expected to reach 71 million by 2030 and 98 million by 2060 when older adults will make up nearly 25% of the population (U.S. National Center for Chronic Disease Prevention Health Promotion, 2021). Age is the leading risk factor for many preval‎ent non-communicable diseases, including cardiovascular and metabolic conditions, neurodegenerative disorders, and cancer (Niccoli and Partridge, 2012). Thus, improving prevention and management of age-related disorders remains of utmost importance for health caregivers in helping the older adults remain healthy as long as possible while tackling the ever-increasing population with effective and safe approaches. Diet appears to be a practical, flexible, and affordable approach that could help older people live longer and healthier lives (Calder et al., 2018), yet the effects of specific dietary components or nutritional formulations in the aging population have yet to be clarified. While the beneficial effects of dietary food components for cognitive function in older adults are well recognized (Ozawa et al., 2021), much less information is available how various nutritional compounds affect other biomarkers of aging. As getting old is accompanied by telomere attrition and DNA damage, any nutraceutical that is able to directly influence telomeres metabolism, slow their deterioration, and diminish aging might extend the life and health span (Vidacek et al., 2017). Among others, hydrogen-rich water (HRW) recently emerged as a novel drinkable dietary product that might favorably affect various aging-related features in interventional trials. For instance, HRW reduces inflammatory responses and prevents programmed cell death (Sim et al., 2020), improves nutrients metabolism (Kajiyama et al., 2008; Song et al., 2013), enhances psychophysiological outcomes (Mizuno et al., 2018), and represses wrinkles formation (Kato et al., 2012). Although promising, the above studies typically recruited mid-age or pre-elderly individuals, administered HRW for a relatively short interval (e.g., seven days to 4 weeks), used open-label or non-randomized research designs, or employed a limited set of aging biomarkers (Xia et al., 2017), leaving many open questions concerning the effects of HRW in older adults. In this randomized controlled pilot trial, we investigated the effects of 6-month HRW intake on several molecular and phenotypic biomarkers of aging in older adults aged 70 years and over. We hypothesized that drinking HRW would improve quantitative indicators of aging, including telomere length and DNA methylation, brain metabolism, cognitive and physical functioning, and skin viability.

Section snippetsParticipants

Forty older adults signed an informed consent to participate in this randomized placebo-controlled parallel-group interventional trial voluntarily. The inclusion criteria were: age 70 years and over (with at least 20% of participants aged over 80 years), body mass index normal or overweight range, no current acute disorders or major chronic diseases (e.g., cancer, neurodegenerative disorders, stroke, psychiatric diseases), able to read and understand written consent form, and willing to take

Results

Forty older adults (mean age 76.0 ± 5.6 years, weight 78.2 ± 16.1 kg, height 167.5 ± 11.5 cm; 20 women) were enrolled in this pilot trial; the average duration of education was 13.0 ± 4.5 years. A total of thirty-four participants (n = 34) completed the follow-up measures, with six subjects dropped out from the study (four from the HRW group and two participants from the control group) due to the reasons not related to the study per se. The volunteers reported no major side effects that

Discussion

This is the first study that comprehensively eval‎uated the effectiveness and safety of medium-term intake of hydrogen-rich water on molecular and phenotypic biomarkers of aging in a cohort of men and women aged 70 years and older. We found that drinking HRW for six months was harmless, and favorably affected several aging-related features, including telomere length, lower body strength, general pain, and brain metabolism indices, and tended to improve DNA methylation, antioxidant status, sleep

Ethical review

The study was approved by the local IRB at the University of Novi Sad (# 46-06-01/2020-1), with the study systematized following the Declaration of Helsinki and International Conference of Harmonization Efficacy Guidelines E6.

Informed consent

All participants signed an informed consent to voluntarily participate in this trial.

Data availability statement

The data that support the findings of this study have already been included in the manuscript. Raw data are available from the corresponding author upon reasonable request.