High doses of caffeine reduce <i>in vivo</i> osteogenic activity in prepubertal rats

Shin, Jaekyung; Choi, Yuri; Kim, Jisook; Yu, A-Ram; Shin, Jisoo; Choi, Yun-Young; Roh, Jaesook

doi:10.1111/joa.12332

Cited by 14 publications

(40 citation statements)

References 32 publications

(81 reference statements)

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“…Consistent with previous reports (5,8), we observed significant reductions in both body weight gain and food intake in caffeine-fed immature animals (Fig. 1A, 1C), indicating that reduced body weight gain can be attributed mainly to decreased food intake.…”

Section: Discussionsupporting

confidence: 93%

The Effects of Caffeine on the Long Bones and Testes in Immature and Young Adult Rats

2017

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This study was to evaluate the age-dependent effects of caffeine exposure on the long bones and reproductive organs using male rats. A total of 15 immature male rats and 15 young adult male rats were allocated randomly to three groups: a control group and two groups fed caffeine with 120 and 180 mg/kg/day for 4 weeks. Exposure to caffeine at either dose significantly reduced body weight gain; a proportional reduction in muscle and fat mass in immature animals, whereas a selective reduction in fat mass with relatively preserved muscle mass in young adult animals. The long bones of immature rats exposed to caffeine were significantly shorter and lighter than those of control animals along with decreased bone minerals. However, there was no difference in the length or weight of the long bones in young adult rats exposed to caffeine. Exposure to caffeine reduced the size and absolute weight of the testes significantly in immature animals in comparison to control animals, but not in young adult animals exposed to caffeine. In contrast, the adrenal glands were significantly heavier in caffeine-fed young adult rats in comparison to control animals, but not in caffeine-fed immature rats. Our results clearly show that the negative effects of caffeine on the long bones and testes in rats are different according to the age of the rat at the time of exposure, and might therefore be caused by changes to organ sensitivity and metabolic rate at different developmental stages. Although the long bones and testes are more susceptible to caffeine during puberty, caffeine has negative effects on body fat, bone minerals and the adrenal glands when exposure occurs during young adulthood. There is a need, therefore, to educate the public the potential dangers of caffeine consumption during puberty and young adulthood.

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Section: Discussionsupporting

confidence: 93%

The Effects of Caffeine on the Long Bones and Testes in Immature and Young Adult Rats

2017

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“…We have also demonstrated that peripubertal exposure to caffeine clearly reduced the in vivo metabolic activity of the epiphyseal growth plate and markedly delayed the closing rate of the growth plate in young, rapidly growing animals (Shin et al. ). These negative influences of caffeine on the growth plate were observed in a dose‐dependent manner even after short‐term exposure (Choi et al.…”

Section: Introductionmentioning

confidence: 88%

“…The doses (120‐ or 180‐mg) levels were previously shown to inhibit the growth of long bones in immature male rats (Shin et al. ; Choi et al. ).…”

Section: Methodsmentioning

confidence: 99%

Longitudinal bone growth is impaired by direct involvement of caffeine with chondrocyte differentiation in the growth plate

Choi

Kim

et al. 2016

Journal of Anatomy

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We showed previously that caffeine adversely affects longitudinal bone growth and disrupts the histomorphometry of the growth plate during the pubertal growth spurt. However, little attention has been paid to the direct effects of caffeine on chondrocytes. Here, we investigated the direct effects of caffeine on chondrocytes of the growth plate in vivo and in vitro using a rapidly growing young rat model, and determined whether they were related to the adenosine receptor signaling pathway. A total of 15 male rats (21 days old) were divided randomly into three groups: a control group and two groups fed caffeine via gavage with 120 and 180 mg kg day for 4 weeks. After sacrifice, the tibia processed for the analysis of the long bone growth and proliferation of chondrocytes using tetracycline and BrdU incorporation, respectively. Caffeine-fed animals showed decreases in matrix mineralization and proliferation rate of growth plate chondrocytes compared with the control. To evaluate whether caffeine directly affects chondrocyte proliferation and chondrogenic differentiation, primary rat chondrocytes were isolated from the growth plates and cultured in either the presence or absence of caffeine at concentrations of 0.1-1 mm, followed by determination of the cellular proliferation or expression profiles of cellular differentiation markers. Caffeine caused significant decreases in extracellular matrix production, mineralization, and alkaline phosphatase activity, accompanied with decreases in gene expression of the cartilage-specific matrix proteins such as aggrecan, type II collagen and type X. Our results clearly demonstrate that caffeine is capable of interfering with cartilage induction by directly inhibiting the synthetic activity and orderly expression of marker genes relevant to chondrocyte maturation. In addition, we found that the adenosine type 1 receptor signaling pathway may be partly involved in the detrimental effects of caffeine on chondrogenic differentiation, specifically matrix production and mineralization, as evidenced by attenuation of the inhibitory effects of caffeine by blockade of this receptor. Thus, our study provides novel information on the integration of caffeine and adenosine receptor signaling during chondrocyte maturation, extending our understanding of the effect of caffeine at a cellular level on chondrocytes of the growth plate.

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“…12 The highest dose (120 mg/kg) was chosen in this study based on the study, which showed no renal toxicity and demonstrated inhibition of long bone growth in prepubertal rats. 13 Thus, the highest dose in the study was chosen to investigate the effect of caffeine on longitudinal bone growth in a timedependent manner within the safe range of renal toxicity. The other two doses (20 and 60 mg/kg) were employed to determine whether the effects noted at the 120 mg dose were present in a dose-related manner.…”

Section: Animalsmentioning

confidence: 99%

“…In fact, based on Simmons Teen Survey data (an analysis of adolescent purchasing), the Mintel International Group reported in 2007 that 31% of [12][13][14][15][16][17] year-olds are reported to be regular consumers of energy drinks in the United States. 1 Among children and adolescents, energy drinks are popularly used for performance enhancement, increased concentration, and wakefulness.…”

Section: Introductionmentioning

confidence: 98%

Peripubertal Caffeine Exposure Impairs Longitudinal Bone Growth in Immature Male Rats in a Dose- and Time-Dependent Manner

Choi

Kim

et al. 2016

Journal of Medicinal Food

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This study investigated the dose- and time-dependent effects of caffeine consumption throughout puberty in peripubertal rats. A total of 85 male SD rats were randomly divided into four groups: control and caffeine-fed groups with 20, 60, or 120 mg/kg/day through oral gavage for 10, 20, 30, or 40 days. Caffeine decreased body weight gain and food consumption in a dose- and time-dependent manner, accompanied by a reduction in muscle and body fat. In addition, it caused a shortening and lightening of leg bones and spinal column. The total height of the growth plate decreased sharply at 40 days in the controls, but not in the caffeine-fed groups, and the height of hypertrophic zone in the caffeine-fed groups was lower than in the control. Caffeine increased the height of the secondary spongiosa, whereas parameters related to bone formation, such as bone area ratio, thickness and number of trabeculae, and bone perimeter, were significantly reduced. Furthermore, serum levels of IGF-1, estradiol, and testosterone were also reduced by the dose of caffeine exposure. Our results demonstrate that caffeine consumption can dose- and time-dependently inhibit longitudinal bone growth in immature male rats, possibly by blocking the physiologic changes in body composition and hormones relevant to bone growth.

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High doses of caffeine reduce in vivo osteogenic activity in prepubertal rats

Cited by 14 publications

References 32 publications

The Effects of Caffeine on the Long Bones and Testes in Immature and Young Adult Rats

The Effects of Caffeine on the Long Bones and Testes in Immature and Young Adult Rats

Longitudinal bone growth is impaired by direct involvement of caffeine with chondrocyte differentiation in the growth plate

Peripubertal Caffeine Exposure Impairs Longitudinal Bone Growth in Immature Male Rats in a Dose- and Time-Dependent Manner

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