Endo et al. Journal of Physiological Anthropology 2014, 33:11
http://www.jphysiolanthropol.com/content/33/1/11

SHORT REPORTOpen Access

Acute responses of regional vascular conductanceto oral ingestion of fructose in healthy young
humansMasako Y Endo1, Chizuko Fujihara1, Chinami Yamazaki1, Hideaki Kashima1, Kouhei Eguchi1, Akira Miura1,
Yoshiyuki Fukuoka2 and Yoshiyuki Fukuba1*

Abstract
Background: Recently, it was reported in healthy young subjects that fructose containing drinks increased bloodpressure acutely, without any apparent change in total vascular conductance (TVC). However, because it is wellknown that the splanchnic vasculature is dilated by oral fructose ingestion, it is assumed to be the concomitantvasoconstriction in other peripheral region(s) that is responsible for this finding. Thus, the purpose of this study was
to determine the acute response of regional VC to oral fructose ingestion in young healthy humans.
Results: In 12 healthy young subjects, mean arterial blood pressure (MAP), heart rate, cardiac output, and bloodflow (BF) in the superior mesenteric (SMA), brachial (BA), and popliteal (PA) arteries, in addition to forearm skin BF,
were measured continuously for 2 h after ingestion of 400 ml fructose solution (containing 50 g fructose). Regional
VC was calculated as BF/MAP. MAP increased for 120 min after fructose ingestion without any change in TVC. While
VC in the SMA was elevated after ingestion, VC in BA and PA and forearm skin decreased.
Conclusions: While TVC was apparently unchanged during the 2 h after fructose ingestion, there were coincident
changes in regional VCs in the peripheral circulation, but no net change in TVC.
Keywords: fructose, blood pressure, vascular conductance, central circulation, peripheral circulation

BackgroundIn recent decades, daily consumption of dietary fructose
has increased gradually. In addition to fruit, carbonatedbeverages containing a form of high-fructose corn syrup
have been implicated in the increase [1]. Long-term consumption of fructose results in an increase in plasma triglycerides in humans and animals [2-6], and is considereda significant dietary problem in advanced countries associated with obesity and arteriosclerosis [7-9]. Several recent
studies have suggested that dietary fructose consumption
may lead to the development of cardiovascular diseases
such as hypertension [5,8,10,11]. The current understanding to the background of fructose-derived hypertension is
unclear as to whether overconsumption of fructose itself
induced the elevation of BP directly or indirectly (via
* Correspondence: fukuba@pu-hiroshima.ac.jp
1
Department of Exercise Science and Physiology, School of Health Sciences,
Prefectural University of Hiroshima, 1-1-71 Ujina-higashi, Minami-ku, Hiroshima734-8558, Japan
Full list of author information is available at the end of the article

hyperuricemia, which is subsequently followed by activation of the rennin-angiotensin-aldosterone system anddamage to the renal tubule [11,12]).
The blood pressure (BP) was greater after consumption of a high fructose diet for eight weeks compared withrats consuming a normal diet in rats [11]. In older people,
the BP acutely increased following ingestion of fructosecontaining drinks [13]. Even in healthy young subjects,
Brown et al. [7] showed that oral consumption of a 50-g
pure fructose-containing drink rapidly increased BP, which
was sustained for at least a few hours, whereas there wasno comparable effect after consumption of either a glucosecontaining drink or water [7]. They suggested that fructosespecific acute elevations in BP were mainly mediated not by
a decreased peripheral vascular response (that is, no change
in total vascular conductance, TVC), but by a sustained elevation of cardiac output (CO). However, it is well known
that fructose ingestion results in a slight, but significant,increase in acute splanchnic circulation [14]. Together© 2014 Endo et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain
Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article,
unless otherwise stated.

Endo et al. Journal of Physiological Anthropology 2014, 33:11
http://www.jphysiolanthropol.com/content/33/1/11

with these results, it is hypothesized that regional VC in
areas such as the viscera, limbs, and/or skin would beacutely changed, even while TVC remains apparently
unchanged. Therefore, we did this study as a pilot to reconfirm the results by Brown et al. [7], including the simultaneous measurements of peripheral VCs in several targeted
arteries with our technique (that is, pulsed Doppler ultrasound sonography).
Based on the findings above, focusing on regional VC
after fructose ingestion is important because the accumulation of acute effect(s) to regional cardiovascular regulation may be a precursor to a more chronic phenomenon,
that is, fructose-induced hypertension. Thus, the purposeof this study was to determine acute responses of regional
VC to oral fructose ingestion in young healthy humans.

Methods
Subjects

Twelve healthy young subjects (four males, eight females)
were studied. The mean (± SEM) age, height, and bodymass of the subjects was 21.5 ± 1.4 years, 160.0 ± 6.4 cm,
and 50.8 ± 4.3 kg, respectively. All subjects were informedof the purpose, protocol, and risks associated with theprocedures before giving written informed consent toparticipate in the study, which was approved by the local
Ethics Committee of Hiroshima and was conducted inaccordance with the Declaration of Helsinki. The menstrual
cycle in the female subjects was not controlled.
ProtocolThe subjects arrived at the laboratory in the morning aftera 12-hour fast. After baseline measurements for 30 min,the subjects ingested a 400-ml fructose solution. Then, thesubjects rested for 120 min in a supine position, except at
the time of drink ingestion. The subjects consumed thedrink within 3 min in a sitting position. The test drink
was a water-based solution containing 50 g fructose. Unsweetened lemon juice (10 ml) was added to the drink toprovide a more appetizing taste for the participants. The
ambient temperature of the experimental room was kept
at 23 ± 0.5 °C and 40-50% relative humidity by a thermal
feedback device.
Measurements

Heart rate (HR) was continuously measured using anelectrocardiogram (BPM-300, Nippon Colin Co., Komaki,
Japan) throughout the protocol. Measurement of meanarterial pressure (MAP) was performed using the same
instrument on the left arm by an automated oscillometric method every 10 min. The beat-to-beat stroke volume (SV) was estimated using the model flow method(Finometer PRO, Finapres Medical Systems, Amsterdam,
The Netherlands) on the left middle finger, which provides
a reliable estimate of changes in SV, even during exercise

Page 2 of 5

in healthy humans [15]. Cardiac output (CO) and total
vascular conductance (TVC) were calculated using thefollowing equations:
CO ¼ SV  HR and TVC ¼ CO=MAP; respectively:
Blood velocity (BV) and vessel diameter were obtainedon a beat-by-beat basis using pulsed Doppler ultrasoundsonography (LOGIQ S6, GE Medical Systems, Tokyo,
Japan) on the right brachial and popliteal arteries (BA andPA) every 20 min with a 5.0 MHz linear probe, and with a
3.5-MHz convex probe on the superior mesenteric andright renal arteries (SMA and RA). The BA measurement
was taken 5 cm from the axilla, and the PA measurement
was taken on the popliteal fossa. The locations of SMA
and RA measurements were within 1 to 3 cm from thebranch of each artery. To obtain the highest quality
Doppler tracings, the optimal positions of the Doppler
probe for each subject were determined in a preliminary
trial (that is, the proper alignment of the ultrasoundbeam with the artery). After adjustment of the sample
volume width to cover the target arterial diameter, theDoppler probe was kept constant on the subject’s skinsurface. Ultrasound insonation resulted in an angle between 45 and 60°. To avoid the effect of movement of the
SMA and RA during the cyclic phase of breathing, subjects were told to hold their breath for approximately 10 swith natural expiration. The BV at each time point was
averaged during approximately 10 to 20 cardiac cycles.
Vessel diameter was obtained by analyzing pictures ofthe vertical section of blood vessels using a B-mode
ultrasound. BV was calculated as:
BF ¼ BV  ðvessel diameterÞ2  π=4:The details were described in our previous studies[16,17]. These BFs were always measured in the order BA,
PA, SMA, and RA within 5 min at 20-min intervals. The
VC of each artery was calculated using the following
equation:
VC ¼ BF=MAP:The BF of skin in the right forearm was measured
continuously using a laser rheometer (ALF21; Advance,
Tokyo, Japan).
Statistical analysis

All data are expressed as mean ± SEM. The effect of timeon the variables was examined using repeated measures
one-way analysis of variance (ANOVA). When significant
differences were detected, Dunnett’s post-hoc test wasused to reveal the effect of time against the baseline (thatis, values before ingestion). The level of statistical significance was set at P <0.05. All analyses were performed
using SPSS 12.0 for Windows (SPSS, Chicago, IL, USA).

Endo et al. Journal of Physiological Anthropology 2014, 33:11
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MAP (mmHg)

78
76
74
72
70
68

HR (beats/min)

68
64
60
56
52

SV (ml/beat)

80
76
72
68
64
60

CO (ml/min)

4800
4600
4400
4200
4000
3800

TVC (ml/min/mmHg)

Results and discussion
Changes in MAP, HR, SV, CO, and TVC after ingestion
compared with baseline (that is, before ingestion) are
shown in Figure 1. MAP increased significantly after ingestion and remained elevated for 120 min. HR and CO
increased gradually and were significantly higher compared with baseline from approximately 60 min after ingestion. TVC did not change significantly, but there wasa trend to increase gradually with time.
VC in several peripheral regions is shown in Figure 2.
VCs in SMA and RA in the rest were compatible tothose which were obtained in the similar conditions in
the previous studies [16,17]. VC in the BA and PA decreased rapidly after ingestion and remained decreased
for approximately 90 min. In contrast, VC in the SMA
increased rapidly for the first 20 to 40 min after ingestion. VC in the RA was decreased during the latter halfof the protocol (that is, approximately 90 to 120 min).
Finally, the VC of forearm skin decreased after ingestion
and returned to baseline at approximately 90 min.
The purpose of this study was to determine acute responses of regional VC to oral fructose ingestion in young
healthy humans. As expected from a previous study [7],oral fructose ingestion initiated an acute and significant
elevation of MAP lasting for at least two hours. This waspartially induced by a change not in TVC, but increased
CO via a sustained elevation in HR. While TVC wasapparently unchanged during the two hours after ingestion, there were changes in regional VC, but no net
change in TVC.
The increase in BP associated with oral fructose ingestion was characterized by gradual increases in CO andHR, but no compensatory reduction in TVC (Figure 1).
The acute BP elevation was partially induced by an elevation in CO via a concomitant increase in HR. This
result is in agreement with previous studies [7,18]. Indirect measures using HR variability have indicatedparasympathetic withdrawal and sympathetic activationcompared with baseline [7]. Vollenweider et al. [19] showedno change in muscle sympathetic nervous activity in thelower limbs during continuous venous infusion of fructose
for two hours. The increased HR in this study seemed to be
induced by the parasympathetic withdraw, while the mechanism of the cardiac autonomic stimulation following ingestion of fructose remains to be established.
The novel finding in the present study was that overthe 120 min after fructose drink ingestion, the BP showed
the acute elevation. During such duration, while the TVC
was unchanged, the regional VCs in several peripheral vasculatures showed different features of changes (Figure 2).
In detail, during the first 60 min after oral fructose ingestion, VC in the SMA (supply routes to the duodenum,
small intestine, ascending colon, transverse colon, and pancreas) rapidly increased, whereas VC in the BA and PA

Page 3 of 5

64
60
56
52
48
pre

20

40

60

80 100 120

time (min)Figure 1 Changes in circulation parameters before and afteringestion of fructose. Changes in mean arterial pressure (MAP),
heart rate (HR), stroke volume (SV), cardiac output (CO), and total
vascular conductance (TVC) are shown from the top. Data: mean ± SEM*:
versus pre-ingestion (P <0.05).

Endo et al. Journal of Physiological Anthropology 2014, 33:11
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Page 4 of 5

BA

(ml/min/mmHg)

PA(ml/min/mmHg)

SMA(ml/min/mmHg)

RA

2.4

8.0

4.0

Abbreviations
BA: brachial artery; BF: blood flow; BV: blood velocity; CO: cardiac output;
HR: heart rate; MAP: mean arterial blood pressure; PA: popliteal artery;
RA: renal artery; SMA: superior mesenteric artery; SV: stroke volume; TVC: total
vascular conductance; VC: vascular conductance.

10.0

Competing interests
The authors declare that they have no competing interests.

(ml/min/mmHg/100g)

skin in forearm

2.0(ml/min/mmHg)[18] demonstrated acute increased serum norepinephrine levels during one hour after oral fructose ingestion.

Conclusions/perspectives
We observed systemic and peripheral circulatory responses
to oral fructose ingestion over a 2-hour period. Fructose
ingestion was associated with an acute elevation in BP,
which was associated with an increase in CO. Althoughfructose ingestion did not change TVC, there were several different changes in regional vascular responses
over the period, which may, with repeated exposure, increase the risk of hypertension-induced arteriosclerosis
and events such as stroke and cardiovascular disease inaddition to hyperlipidemia.

1.6
1.2
0.8
0.4

2.0
1.6
1.2

7.0
6.0
5.0

8.0

Authors’ contributions
Contribution of each author is as follows: MYE and YF conceived this study,
outlined the method, directed the experiments, and interpreted the results.
The majority of the article was written by MYE, CF, HK, and YF. CY and KE
contributed to the experiments, data analyses, and manuscript preparation.
CY, HK, and AM discussed the manuscript and aided in revising it criticallyfor important intellectual content with MYE and YF. All authors approved themanuscript.

6.0
4.0
0.020
0.018
0.016
0.014
0.012

pre

20

40

60

80

100 120time (min)Figure 2 Change in regional vascular conductance (VC) before
and after ingestion of fructose. Changes in VC in the brachialartery (BA), popliteal artery (PA), superior mesenteric artery (SMA),
right renal artery (RA), and forearm skin are shown from the top.
Data: mean ± SEM*: versus pre-ingestion (P <0.05).

(supply to mainly skeletal muscles and skin) was reduced.
During the subsequent hour (that is, 60 to 120 min), VC in
the SMA had already returned to baseline, whereas VC in
the RA gradually decreased. In addition, VC in the BA, PA,
and forearm skin gradually returned to baseline (that is,the changes in VC among the BA, PA, and forearm skinwere very similar).
These results indicate that, after oral fructose ingestion,
the vascular beds in peripheral limbs (that is, arms andpresumably lower limbs) were vasoconstricted to compensate for vasodilation in the splanchnic region (thatis, SMA) for the digestion and absorption of fructose.
Such peripheral vasoconstriction seems to be derived
from systemic sympathetic activation, since Jansen et al.

Acknowledgements
This study was supported in part by JSPS KAKENHI (#24700701 to Endo,#22370091 to Fukuoka and #23650390 to Fukuba) and the Descente andIshimoto Memorial Foundation for the Promotion of Sports Science.
Author details
1
Department of Exercise Science and Physiology, School of Health Sciences,
Prefectural University of Hiroshima, 1-1-71 Ujina-higashi, Minami-ku, Hiroshima734-8558, Japan. 2Faculty of Health and Sports Science, Doshisha University,
Kyotanabe, Kyoto 610-0394, Japan.
Received: 3 February 2014 Accepted: 1 May 2014
Published: 17 May 2014
References
1. Rizkalla SW: Health implications of fructose consumption: A review ofrecent data. Nutr Metab 2010, 7:82.
2. Martinez FJ, Rizza RA, Romero JC: High-fructose feeding elicits insulin
resistance, hyperinsulinism, and hypertension in normal mongrel dogs.
Hypertension 1994, 3:456–463.
3. Park J, Lemieux S, Lewis GE, Kuksis A, Steiner G: Chronic exogenous insulin
and chronic carbohydrate supplementation increase de novo VLDL
triglyceride fatty acid production in rats. J Lipid Res 1997, 38:2529–2536.
4. Bantle JP, Raatz SK, Thomas W, Georgopoulos A: Effects of dietary fructose
on plasma lipids in healthy subjects. Am J Clin Nutr 2000, 72:1128–1134.
5. Elliott SS, Keim NL, Stern JS, Teff K, Havel PJ: Fructose, weight gain, and theinsulin resistance syndrome. Am J Clin Nutr 2002, 76:911–922.
6. Stanhope KL, Schwarz JM, Keim NL, Griffen SC, Bremer AA, Graham JL,
Hatcher B, Cox CL, Dyachenko A, Zhang W, McGahan JP, Seibert A, Krauss RM,
Chiu S, Schaefer EJ, Ai M, Otokozawa S, Nakajima K, Nakano T, Beysen C,
Hellerstein MK, Berglund L, Havel PJ: Consuming fructose-sweetened, notglucose sweetened, beverages increases visceral adiposity and lipids anddecreases insulin sensitivity in overweight/obese humans. J Clin Invest 2009,
119:1322–1334.

Endo et al. Journal of Physiological Anthropology 2014, 33:11
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7.

8.
9.
10.

11.

12.

13.

14.

15.

16.

17.

18.

19.

Page 5 of 5

Brown CM, Dulloo AG, Yepuri G, Montani JP: Fructose ingestion acutely
elevates blood pressure in healthy young humans. Am J Physiol 2008,
294:R730–R737.
Madero M, Perez-Pozo SE, Jalal D, Johnson RJ, Laura G: Dietary Fructose
and Hypertension. Curr Hypertens Rep 2011, 13:29–35.
Chong MF, Fielding BA, Frayn KN: Mechanisms for the acute effect offructose on postprandial lipemia. Am J Clin Nutr 2007, 85:1511–1520.
Machi JF, Bernardes N, Mostarda C, Moraes-Silva IC, Irigoyen MC, De Angelis K,
Wichi RB: Walking promotes metabolic and baroreflex sensitivity improvementin fructose-fed male rats. Eur J Appl Physiol 2013, 113:41–49.
Sanchez-Lozada LG, Tapia E, Jimenez A, Bautista P, Cristobal M,
Nepomuceno T, Soto V, Avila-Casado C, Nakagawa T, Johnson RJ,
Herrera-Acosta J, Franco M: Fructose-induced metabolic syndrome isassociated with glomerular hypertension and renal microvasculardamage in rats. Am J Physiol 2007, 292:F423–F429.
Uezono K, Sakaki H, Kawasaki T, Kumagai S: Differences in glucose metabolism
and renin-angiotensin-aldosterone system between normotensive andborderline-hypertensive male students. -2. from the responses to 75 g
fructose ingestion. J Health Sci 2000, 22:137–142.
Visvanathan R, Chen R, Horowitz M, Chapman I: Blood pressure responses
in healthy older people to 50 g carbohydrate drinks with differing
glycaemic effects. Br J Nutr 2004, 92:335–340.
Brundin T, Wahren J: Whole body and splanchnic oxygen consumption
and blood flow after oral ingestion of fructose or glucose. Am J Physiol
1993, 264:E504–E513.
Sugawara J, Tanabe T, Miyachi M, Yamamoto K, Takahashi K, Iemitsu M,
Otsuki T, Homma S, Maeda S, Ajisaka R, Matsuda M: Non-invasive
assessment of cardiac output during exercise in healthy young humans:
comparison between Modelflow method and Doppler echocardiographymethod. Acta Physiol Scand 2003, 179:361–366.
Endo MY, Suzuki R, Nagahata N, Hayashi N, Miura A, Koga S, Fukuba Y:
Differential arterial blood flow response of splanchnic and renal organs
during low-intensity cycling exercise in women. Am J Physiol 2008, 294:
H2322–H2326.
Endo MY, Shimada K, Miura A, Fukuba Y: Peripheral and central vascular
conductance influence on post-exercise hypotension. J Physiol Anthropol
2012, 31:32.
Jansen RW, Penterman BJ, Van Lier HJ, Hoefnagels WH: Blood pressure
reduction after oral glucose loading and its relation to age, bloodpressure and insulin. Am J Cardiol 1987, 60:1087–1091.
Vollenweider P, Tappy L, Randin D, Schneiter P, Jéquier E, Nicod P, Scherrer U:
Differential effects of hyperinsulinemia and carbohydrate metabolism on
sympathetic nerve activity and muscle blood flow in humans. J Clin Invest
1993, 92:147–154.

doi:10.1186/1880-6805-33-11
Cite this article as: Endo et al.: Acute responses of regional vascular
conductance to oral ingestion of fructose in healthy young humans.
Journal of Physiological Anthropology 2014 33:11.

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