Oral supplementation with a combination of l-citrulline and l-arginine rapidly increases plasma l-arginine concentration and enhances NO bioavailability

Murakami, Masahiko; Hayashi, Toshio; Ochiai, Masayuki; Maeda, Morihiko; Yamaguchi, Tomoe; Ina, Koichiro; Kuzuya, Masafumi

doi:10.1016/j.bbrc.2014.10.029

Cited by 102 publications

(86 citation statements)

References 36 publications

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“…As previously reported in animal studies, 17,18) this study was useful in terms of confirming the combination effects on plasma L-arginine increase in humans as well as in animals. One possible reason for this combination effect might be due to the inhibiting effect of L-citrulline on arginase, which metabolizes L-arginine to urea and L-ornithine.…”

supporting

confidence: 75%

“…17) Intriguingly, we recently discovered, in an animal study, that oral supplementation with a combination of L-citrulline and L-arginine efficiently increases plasma L-arginine concentration and peripheral circulation. 18) However, the effects of this combination on humans have not as yet been investigated. We hypothesized that plasma L-arginine would be increased to a greater extent with a combination of L-citrulline and L-arginine, each at half dosage, than by ingesting each of them singly at full dosage.…”

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confidence: 99%

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The effects on plasma L-arginine levels of combined oral L-citrulline and L-arginine supplementation in healthy males

Suzuki

Murakami

Hayashi

et al. 2017

Bioscience, Biotechnology, and Biochemistry

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We investigated the effects of combining 1 g of l-citrulline and 1 g of l-arginine as oral supplementation on plasma l-arginine levels in healthy males. Oral l-citrulline plus l-arginine supplementation more efficiently increased plasma l-arginine levels than 2 g of l-citrulline or l-arginine, suggesting that oral l-citrulline and l-arginine increase plasma l-arginine levels more effectively in humans when combined.

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confidence: 75%

mentioning

confidence: 99%

The effects on plasma L-arginine levels of combined oral L-citrulline and L-arginine supplementation in healthy males

Suzuki

Murakami

Hayashi

et al. 2017

Bioscience, Biotechnology, and Biochemistry

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“…Combination amino acid therapy also warrants consideration. In an animal model, coadministration of arginine and citrulline resulted in a more rapid increase in plasma arginine levels and marked enhancement of NO bioavailability than supplementation of the single amino acids alone 157 . In a murine model, glutamine supplementation improved bioavailability of glutamine and arginine in the fetal plasma and placental fluids 158 .…”

Section: Methods Of Providing Conditionally Essential Amino Acidsmentioning

confidence: 99%

Acquired Amino Acid Deficiencies: A Focus on Arginine and Glutamine

et al. 2017

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Nonessential amino acids are synthesized de novo and therefore not diet dependent. In contrast, essential amino acids must be obtained through nutrition since they cannot be synthesized internally. Several nonessential amino acids may become essential under conditions of stress and catabolic states when the capacity of endogenous amino acid synthesis is exceeded. Arginine and glutamine are 2 such conditionally essential amino acids and are the focus of this review. Low arginine bioavailability plays a pivotal role in the pathogenesis of a growing number of varied diseases, including sickle cell disease, thalassemia, malaria, acute asthma, cystic fibrosis, pulmonary hypertension, cardiovascular disease, certain cancers, and trauma, among others. Catabolism of arginine by arginase enzymes is the most common cause of an acquired arginine deficiency syndrome, frequently contributing to endothelial dysfunction and/or T-cell dysfunction, depending on the clinical scenario and disease state. Glutamine, an arginine precursor, is one of the most abundant amino acids in the body and, like arginine, becomes deficient in several conditions of stress, including critical illness, trauma, infection, cancer, and gastrointestinal disorders. At-risk populations are discussed together with therapeutic options that target these specific acquired amino acid deficiencies.

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“…A rodent study showed that a combination of L‐citrulline and glutathione supplementation was more effective in increasing the plasma NOx concentration than supplementing with L‐citrulline alone (McKinley‐Barnard, Andre, Morita, & Willoughby, ); therefore, the synergism between NO donor and antioxidants could be a strategy to enhance the NO related vasodilation function in lactating sows. Besides, a combination of half dosage of L‐citrulline and half dosage L‐arginine was more effective in increasing plasma NOx concentration and enhancing vasodilation than separately supplemented with a full dosage of L‐citrulline or L‐arginine (Morita et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…The sows were fed either the control diet ( n = 111) or L‐citrulline diet ( n = 110) upon entry to the farrowing house (6 ± 1.8 days [mean ± SD ] before farrowing) until weaning (26 ± 1.5 days lactation). The dosage of the L‐citrulline used in this experiment is based on an experiment by Morita et al, () in the rabbit model, whereby 0.50 g/kg (body weight) via gavage numerically increased the ear blood flow by approximately 7%. Sows were restrict fed 2.5–4 kg from entry until day 3 after farrowing and then fed ad libitum as previously described (Liu et al, ).…”

Section: Methodsmentioning

confidence: 99%

Effects of L‐citrulline supplementation on heat stress physiology, lactation performance and subsequent reproductive performance of sows in summer

Liu¹,

Ruyter²,

Athorn³

et al. 2018

Animal Physiology Nutrition

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Lactating sows are susceptible to heat stress (HS). Part of the thermoregulatory response to HS is to increase peripheral blood flow, which is mediated in part by the vasodilator, nitric oxide (NO). Therefore, the aim of this experiment was to determine the effect of supplementation of L‐citrulline, a NO precursor, on symptoms of HS, lactation performance and subsequent reproductive performance of sows in summer. A total of 221 summer farrowing mixed parity sows were fed either a control diet or supplemented with 1% L‐citrulline upon entry to the farrowing house (6 ± 1.8 days for mean ± standard deviation [SD] before farrowing) until weaning (26 ± 1.5 days). The average daily minimum and maximum temperature in the farrowing house was 21.0 ± 1.88 and 29.2 ± 3.82°C (mean ± SD). Rectal temperature, respiration rate, and plasma and urinary nitrite and nitrate (NOx) of sows were measured on the 19th day post‐farrowing. Supplemental L‐citrulline in the diet did not affect the number of piglets born alive, feed intake of sows, body weight or backfat thickness of sows at weaning, or litter weight gain. L‐citrulline tended to reduce piglet pre‐weaning mortality rate from 18.6% to 15.6% (p = 0.058). L‐citrulline reduced the respiration rate of sows compared to the control diet at 17:00 hr (Time × Diet, p < 0.001); however, rectal temperature was not affected. L‐citrulline tended to increase urinary NOx concentrations (127 vs. 224 µM, p = 0.057) but not plasma NOx concentrations. L‐citrulline did not affect farrowing rate or number of piglets born alive in the subsequent parity. In conclusion, L‐citrulline supplementation reduced respiration rate of lactating sows and reduced piglet pre‐weaning mortality rate in summer. Whether the effects were due to a NO‐dependent mechanism requires further validation.

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Oral supplementation with a combination of l-citrulline and l-arginine rapidly increases plasma l-arginine concentration and enhances NO bioavailability

Abstract: Our data show for the first time that a combination of oral L-citrulline and L-arginine effectively and rapidly augments NO-dependent responses at the acute stage. This approach may have clinical utility for the regulation of cardiovascular function in humans.

Cited by 102 publications

References 36 publications

The effects on plasma L-arginine levels of combined oral L-citrulline and L-arginine supplementation in healthy males

The effects on plasma L-arginine levels of combined oral L-citrulline and L-arginine supplementation in healthy males

Acquired Amino Acid Deficiencies: A Focus on Arginine and Glutamine

Effects of L‐citrulline supplementation on heat stress physiology, lactation performance and subsequent reproductive performance of sows in summer

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