Nocturnal branched‐chain amino acid administration improves protein metabolism in patients with liver cirrhosis: comparison with daytime administration

Fukushima, Hideki; Miwa, Yoshiyuki; Ida, Erika; Kuriyama, Shoko; Toda, Katsuhisa; Shimomura, Yoriko; Sugiyama, Akihiko; Sugihara, Junichi; Tomita, Eiichi; Moriwaki, Hisataka

doi:10.1177/0148607103027005315

Cited by 57 publications

(73 citation statements)

References 27 publications

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“…However, glutamate, ornithine, proline, and two of the BCAAs, isoleucine and valine, had 24-h rhythms with significant fits to a cosine curve, irrespective of the presence or absence of sleep or meals, with levels peaking at night (between 21:00 and 01:30 h). Knowledge of this daily variation in isoleucine and valine may aid in optimizing their therapeutic efficacy, for example, to improve protein metabolism in patients with liver cirrhosis, in whom administration of BCAAs at night is known to be more effective than during the day (52). Further characterization of the endogenous fluctuations of metabolites such as BCAAs under different conditions (e.g., in type 2 diabetes) may help to generate testable hypotheses relating to the best time of day to administer treatments most effectively.…”

Section: Discussionmentioning

confidence: 99%

Effect of sleep deprivation on the human metabolome

Davies

Ang

Revell

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

436

371

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Sleep restriction and circadian clock disruption are associated with metabolic disorders such as obesity, insulin resistance, and diabetes. The metabolic pathways involved in human sleep, however, have yet to be investigated with the use of a metabolomics approach. Here we have used untargeted and targeted liquid chromatography (LC)/MS metabolomics to examine the effect of acute sleep deprivation on plasma metabolite rhythms. Twelve healthy young male subjects remained in controlled laboratory conditions with respect to environmental light, sleep, meals, and posture during a 24-h wake/ sleep cycle, followed by 24 h of wakefulness. Two-hourly plasma samples collected over the 48 h period were analyzed by LC/MS. Principal component analysis revealed a clear time of day variation with a significant cosine fit during the wake/sleep cycle and during 24 h of wakefulness in untargeted and targeted analysis. Of 171 metabolites quantified, daily rhythms were observed in the majority (n = 109), with 78 of these maintaining their rhythmicity during 24 h of wakefulness, most with reduced amplitude (n = 66). During sleep deprivation, 27 metabolites (tryptophan, serotonin, taurine, 8 acylcarnitines, 13 glycerophospholipids, and 3 sphingolipids) exhibited significantly increased levels compared with during sleep. The increased levels of serotonin, tryptophan, and taurine may explain the antidepressive effect of acute sleep deprivation and deserve further study. This report, to our knowledge the first of metabolic profiling during sleep and sleep deprivation and characterization of 24 h rhythms under these conditions, offers a novel view of human sleep/wake regulation.circadian rhythms | total sleep deprivation | melatonin | depression | biomarker C ircadian clocks control the timing of most daily biological processes, including cyclic changes in metabolism and the sleep/wake cycle (1). There is a clear link between the circadian timing system and metabolism (2-4), with disrupted circadian rhythms, sleep restriction, and sleep deprivation associated with metabolic disorders (obesity, insulin resistance, diabetes) and cardiovascular disease (5-8). The underlying mechanisms linking metabolic disease, circadian clock misalignment, and sleep restriction are the subject of current research, elucidation of which will require a global "systems" approach (9). Transcriptomic studies have shown that rhythmic gene expression may be affected by sleep restriction, sleep deprivation, and mistimed sleep (10-12), but, as yet, no studies have directly investigated the effect that sleep and sleep deprivation may have on the metabolic profile. Metabolic profiling, or "metabolomics," is the profiling of small-molecule metabolites and offers the potential to characterize specific metabolic phenotypes associated with disrupted circadian timing and sleep loss. Metabolomics has an advantage over other "omics" techniques, in that it directly samples the metabolic changes in an organism and integrates information from changes at the gene, transcript, an...

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Section: Discussionmentioning

confidence: 99%

Effect of sleep deprivation on the human metabolome

Davies

Ang

Revell

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

436

371

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“…Table 3 provides a summary of all studies completed that examined BCAA supplementation in older adults (average age >60) with liver cirrhosis. Of the 9 studies completed to date, 7 showed improvements in nitrogen balance, ratio of branched chain to aromatic amino acids, serum albumin, fuel metabolism, quality of life scores, liver function, muscle mass, and survival, as well as decreases in serum ketone bodies and muscle cramps [72][73][74][75][83][84][85] . Two of the studies showed no significant differences between the treatment group and the control group [38,82] ; however, they both included very small sample sizes.…”

Section: Branched Chain Amino Acid Supplementation In Older Adults Wimentioning

confidence: 99%

“…Protein in older cirrhotic adults Table 1 Summary of studies examining safety of increased protein intake in liver disease. Author, Year Greenberger et al [36] Keshavarian et al [37] 1984 Christie et al [38] Bunout D et al [39] 1989 Swart GR et al [40] 1989 Cabre E et al [45] 1990 Bianchi et al [41] 1993 Kearns et al [24] 1995 Nielsen et al [42] 1995 Cordoba et al [43] [57] 2000 Yamauchi et al [75] 2001 YamanakaOkumura et al [68] 2006 Fukushima et al [72] 2003 Sako et al [73] 2003 Nakaya et al [74] 2007 YamanakaOkumura et al [76] …”

Section: Branched Chain Amino Acid Supplementation In Older Adults Wimentioning

confidence: 99%

“…Author, Year Christie et al [38] 1985 Marchesini et al [83] 1990 Yamauchi et al [75] 2001 Fukushima et al [72] 2003 Sako et al [73] 2003…”

Section: Length Of the Studymentioning

confidence: 99%

“…A summary of studies providing late evening or overnight supplementation to older adults (average age >60) with cirrhosis can be found in table 2. Of the 7 studies completed to date, all showed various positive benefits including improvements in nitrogen balance, ratio of branched chain to aromatic amino acids, serum albumin, fuel metabolism, and quality of life scores and decreases in serum ketone bodies and muscle cramps [57,68,[72][73][74][75][76] . The majority of the studies lasted 3 months or less, with one being 12 months.…”

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confidence: 99%

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Protein Recommendations for Older Adults with Cirrhosis: A Review

Iiames

Logomarsino

2015

Journal of Gastroenterology and Hepatology Research

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Protein intake has a key role in liver cirrhosis in older adults. However, types and amounts of protein intake in cirrhosis have been controversial. The aim of this paper is to investigate the optimal protein intake for management of cirrhosis and prevention of hepatic encephalopathy in older adults. Protein restriction of 0.6 g/kg/d has traditionally been used as medical nutrition therapy in liver cirrhosis. However, recent evidence has shown that protein restrictions have many negative consequences for older adults with cirrhosis. Current research indicates protein intakes of 1.2-1.5 g/ kg/d in liver cirrhosis; however, many older adults do not consume this amount. Strategies to help increase protein intake and manage cirrhosis include ensuring adequate protein at every meal through either regular intake or supplementation, protein supplementation prior to bedtime or overnight, and supplementation with branchedchain amino acids. An emphasis on vegetable protein versus animal protein is probably not an advantageous treatment option because of lack of conclusive evidence regarding benefits and potential negative side effects. and progression of chronic liver disease and cirrhosis.There are several different factors that naturally occur in older adulthood that help contribute to the development of chronic liver disease and cirrhosis. After reaching maximum size in early adulthood, the liver steadily decreases in both size and the amount of blood flow it receives, leading to decreased function and efficiency over time [10] . Also, increased ammonia production and bacterial overgrowth are common in older adulthood, both of which are thought to play a key role in development of hepatic encephalopathy [11] . Older adults tend to have chronic constipation, intestinal dysmotility, and increased colonic transit time, which predisposes them to increased ammonia production [12] . Finally, older adulthood is associated with a higher incidence of diabetes, which is strongly correlated to progression of liver cirrhosis [13] . Pathogenesis of malnutrition in older adults with cirrhosisIt is estimated that 20% of patients with compensated cirrhosis and 60% of patients with decompensated cirrhosis have malnutrition [14] . In older adults, protein energy malnutrition is associated with high health care costs, increased frequency of infection and bedsores, increased morbidity and mortality, and poor physical functioning [4,5] . In canine trials, poor nutritional status has been shown to encourage the development of hepatic encephalopathy [15] . In addition, malnutrition in cirrhosis is positively associated with old age [14] . Multiple factors help contribute to the development of malnutrition in older adults with cirrhosis, including inadequate intake, altered absorption, sarcopenia, and altered metabolism. All causes must be explored and taken into consideration when developing treatment and prevention strategies.In older adults, food intake naturally decreases over time [16] , which promotes the development of malnutri...

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