Food Intake Regulation: Amino Acid Toxicity and Changes in Rat Brain and Plasma Amino Acids

Peng, Yei‐Mei; Gubin, J.; Harper, Alfred E.; Vavich, M. G.; Kemmerer, A. R.

doi:10.1093/jn/103.4.608

Cited by 106 publications

(41 citation statements)

References 30 publications

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“…L-phenylalanine-related effects were also noted in mean food consumption for males and females fed the 5% (w/w) L-phenylalanine diet. Marked suppression of body weight gains and decreased food consumption are known to occur in weanling rats fed diets containing excessive levels (5.0%) of L-phenylalanine (Muramatsu et al,1971) or in rats averaging 170 g at study start and fed 5% L-phenylalanine diets (Peng et al, 1973). The similar, but less profound, effects of L-phenylalanine on a different strain of rats approximately 6-weeks old observed in the current study are consistent with these earlier investigations.…”

Section: Discussionsupporting

confidence: 91%

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28-Day dietary toxicity study of L-phenylalanine in rats

Shibui

Miwa

Kodama

et al. 2014

Fundam. Toxicol. Sci.

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-The purpose of this study was to evaluate the toxicity of L-phenylalanine when administered daily in the diet to rats for at least 28 days. Male and female Crl:CD®(SD)IGS BR rats were assigned to four groups. Each group received diets containing basal diet or 0.5, 1.5, or 5.0% (w/w) L-phenylalanine. There were no clinical or ophthalmic observations that were considered to be related to L-phenylalanine. Effects of L-phenylalanine administration were noted in mean body weights and mean body weight gains in females fed 0.5% and in males and females fed 5.0% (w/w) L-phenylalanine diets. Effects were also noted in mean food consumption in males and females fed the 5.0% (w/w) L-phenylalanine diet. The lower food consumption and body weights of the males and females fed the 5.0% L-phenylalanine diet were considered to be signs of mild toxicity. Administration of L-phenylalanine at a dose of 5.0% of the diet was associated with mildly increased red blood cell count and mildly decreased mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and glucose in females. There were no L-phenylalanine-related toxic changes for organ weight, or macroscopic or microscopic findings. In conclusion, the no-observed-effect level (NOEL) of dietary exposure of male rats to L-phenylalanine is 1.5% (w/w) L-phenylalanine. The NOEL of dietary exposure of female rats to L-phenylalanine is less than 0.5% (w/w) L-phenylalanine. However, the no-observed-adverse-effect level (NOAEL) for males and females is 1.5% (w/w) L-phenylalanine.

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Section: Discussionsupporting

confidence: 91%

“…As for L-phenylalanine, there is some partial toxicological information reported in rats (Muramatsu et al, 1971;Peng et al, 1973) and monkeys (Gibbs et al, 1960). However, its toxicity profile has not yet been comprehensively established, and there are no recent reports regarding orally repeated-dose (dietary) general toxicity of L-phe-…”

Section: Introductionmentioning

confidence: 99%

28-Day dietary toxicity study of L-phenylalanine in rats

Shibui

Miwa

Kodama

et al. 2014

Fundam. Toxicol. Sci.

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“…Peng excess amino acids were elevated 3hr after the force-feeding of young rats with liquid diets containing excess amino acids (16). In the present study, however, the maternal plasma concentrations of the amino acids present in excess in the diet were not markedly elevated, except in groups given excess methionine and threonine .…”

Section: Discussioncontrasting

confidence: 84%

The effects of excess amino acids on maintenance of pregnancy and fetal growth in rats.

Shuji

Niiyama

1982

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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“…Thus, dietary Leu may escape first-pass catabolism in the liver ensuring a rapid flow to the brain. As shown by Peng et al (1973) in rats, ingestion of a diet high in Leu resulted in lower Val, Ile, Met, Phe, Tyr and His concentrations in the brain and in a decrease in the feed intake. It is therefore possible that the excess of Leu competed with Val for transport into the brain, aggravating the effect of Val deficiency in the brain.…”

Section: Discussionmentioning

confidence: 81%

Response of piglets to the valine content in diet in combination with the supply of other branched-chain amino acids

Gloaguen

Floc'H

Brossard

et al. 2011

Animal

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The branched-chain amino acids (BCAA) valine (Val) and isoleucine (Ile) are considered to be among the next-limiting amino acids for growth in piglets. In earlier studies, we estimated the standardized ileal digestible (SID) Val : Lys (lysine) requirement to be at least 70%, whereas the Ile : Lys requirement may be as low as 50%. Because the BCAA partially share a common route of catabolism, the supply of one BCAA may affect the availability of the other BCAA. Four experiments were conducted to determine the response of 6-week-old piglets to the Val supply in relation to the other BCAA. A deficient supply of Val or Ile typically results in a reduction in average daily feed intake (ADFI). Experiment 1 was designed to determine the effect of a limiting Val supply, independent of the effect on feed intake. In a dose-response study using restrictively fed piglets, nitrogen retention did not increase for an SID Val : Lys supply greater than 64%. In the remaining experiments, piglets were offered feed ad libitum using ADFI, average daily gain (ADG) and gain-to-feed ratio as response criteria. The interaction between the Val and leucine (Leu) was studied in Experiment 2 in a 2 3 2 factorial design (60% and 70% SID Val : Lys, and 111% and 165% SID Leu : Lys). Performance was considerably lower in piglets receiving 60% Val : Lys compared with those receiving 70% Val : Lys and was lowest in piglets receiving the diet with low Val and high Leu content. To further evaluate the interaction between Val and Leu, a dose-response study was carried out in which the response to Val supply was studied in combination with high Leu supply (165% Leu : Lys). Using a curvilinear-plateau model, the average SID Val : Lys requirement was 72%. However, low Val supply (60% SID Val : Lys) reduced performance by 13% to 38%, which was much greater than what we observed in earlier studies. Experiment 4 was carried out to test the hypothesis that the Val requirement is not affected by low Ile supply (50% SID Ile : Lys). Performance was not improved for Val : Lys supplies greater than 65%, which may indicate that Ile (and not Lys) was second-limiting in this study. In conclusion, the first response of piglets to deficient Val supply appears to be a reduction in ADFI, rather than a reduction in ADG or nitrogen retention. A large supply of Leu may not affect the Val requirement per se, but may aggravate the consequences of Val deficiency.

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Food Intake Regulation: Amino Acid Toxicity and Changes in Rat Brain and Plasma Amino Acids

Cited by 106 publications

References 30 publications

28-Day dietary toxicity study of L-phenylalanine in rats

28-Day dietary toxicity study of L-phenylalanine in rats

The effects of excess amino acids on maintenance of pregnancy and fetal growth in rats.

Response of piglets to the valine content in diet in combination with the supply of other branched-chain amino acids

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