Evaluation of safety and efficacy profile of Nigella sativa oil as an add-on therapy, in addition to alpha-keto analogue of essential amino acids in patients with chronic kidney disease.

Chronic kidney disease (CKD) encompasses a spectrum of different pathophysio- logic processes associated with abnormal kidney function. When it reaches end-stage renal disease (ESRD), the only option is dialysis and renal transplantation. This is unaffordable by most patients. Hence, newer treatment modalities are being looked for, which can slow down the progression of CKD and delay the development of ESRD. This study aimed to evaluate the efficacy and safety of Nigella sativa oil as an add-on therapy in addition to alpha-keto analogue of essential amino acids in patients with CKD Stages 3 and 4. The study was conducted at a tertiary care center in North India on patients with CKD Stages 3 and 4. It was a prospective, comparative, and open-labeled study. One hundred and fifty patients were enrolled and were randomly divided into two interventional groups. Fourteen patients were lost to follow-up. Group I (control) which had 66 patients received conservative management of CKD consisting of alpha-keto analogue (600 mg tablet three times a day), whereas Group II (test) which had 70 patients received conservative management along with alpha-keto analogue and N. sativa oil (2.5 mL, per orally, once daily) for 12 weeks. Hemogram, renal function, and serum electrolyte tests were done, and adverse events were recorded at baseline and at4, 8, and 12 weeks of treatment. After 12 weeks of treatment, there was a marked improvement in clinical features and biochemical parameters in both the control and test groups. There were a significant reduction in blood urea, serum creatinine, and 24-h total urine protein and a significant improvement in 24-h total urine volume and glomerular filtration rate. N. sativa oil supplementation along with alpha-keto analogue is more more efficacious and safe in delaying the progression of disease patients with CKD Stages 3 and 4.

Essential Amino Acid Supplement Lowers Intrahepatic Lipid despite Excess Alcohol Consumption.

Excess alcohol consumption is a top risk factor for death and disability. Fatty liver will likely develop and the risk of liver disease increases. We have previously demonstrated that an essential amino acid supplement (EAAS) improved protein synthesis and reduced intrahepatic lipid in the elderly. The purpose of this exploratory pilot study was to initiate the evaluation of EAAS on intrahepatic lipid (IHL), body composition, and blood lipids in individuals with mild to moderate alcohol use disorder (AUD). Following consent, determination of eligibility, and medical screening, 25 participants (18 males at 38 ± 15 years/age and 7 females at 34 ± 18 years/age) were enrolled and randomly assigned to one of two dosages: a low dose (LD: 8 g of EAAS twice/day (BID)) or high dose (HD: 13 g of EAAS BID). Five of the twenty-five enrolled participants dropped out of the intervention. Both groups consumed the supplement BID for 4 weeks. Pre- and post-EAAS administration, IHL was determined using magnetic resonance imaging/spectroscopy, body composition was analyzed using dual-energy X-ray absorptiometry, and blood parameters were measured by LabCorp. T-tests were used for statistical analysis and considered significant at p < 0.05. While there was no significant change in IHL in the LD group, there was a significant 23% reduction in IHL in the HD group (p = 0.02). Fat mass, lean tissue mass, bone mineral content, and blood lipids were not altered. Post-EAAS phosphatidylethanol was elevated and remained unchanged in LD at 407 ± 141 ng/mL and HD at 429 ± 196 ng/mL, indicating chronic and excess alcohol consumption. The HD of the proprietary EAAS formulation consumed BID seemed to lower IHL in individuals with mild to moderate AUD. We suggest that further studies in a larger cohort be conducted to more completely address this important area of investigation.

Amino acid supplementation alters bone metabolism during simulated weightlessness.

High-protein and acidogenic diets induce hypercalciuria. Foods or supplements with excess sulfur-containing amino acids increase endogenous sulfuric acid production and therefore have the potential to increase calcium excretion and alter bone metabolism. In this study, effects of an amino acid/carbohydrate supplement on bone resorption were examined during bed rest. Thirteen subjects were divided at random into two groups: a control group (Con, n = 6) and an amino acid-supplemented group (AA, n = 7) who consumed an extra 49.5 g essential amino acids and 90 g carbohydrate per day for 28 days. Urine was collected for n-telopeptide (NTX), deoxypyridinoline (DPD), calcium, and pH determinations. Bone mineral content was determined and potential renal acid load was calculated. Bone-specific alkaline phosphatase was measured in serum samples collected on day 1 (immediately before bed rest) and on day 28. Potential renal acid load was higher in the AA group than in the Con group during bed rest (P < 0.05). For all subjects, during bed rest urinary NTX and DPD concentrations were greater than pre-bed rest levels (P < 0.05). Urinary NTX and DPD tended to be higher in the AA group (P = 0.073 and P = 0.056, respectively). During bed rest, urinary calcium was greater than baseline levels (P < 0.05) in the AA group but not the Con group. Total bone mineral content was lower after bed rest than before bed rest in the AA group but not the Con group (P < 0.05). During bed rest, urinary pH decreased (P < 0.05), and it was lower in the AA group than the Con group. These data suggest that bone resorption increased, without changes in bone formation, in the AA group.

Complication of parenteral nutrition composed of essential amino acids and histidine in adults with renal failure.

This is a case report on six patients with hyperammonemia that developed while they were receiving total parenteral nutrition (TPN) as a component of renal failure therapy. Clinically, the hyperammonemia presented as mental status changes in all six cases. Four of the six patients with renal failure initially received 400 mL Amiyu in 1400 mL 17% glucose (total = 1800 mL TPN-A) administered over each 24-hour period. Two patients had been placed on 400 mL complete amino acid in 1400 mL 17% glucose (total = 1800 mL TPN-C over each 24-hour period) prior to therapy with TPN-A. Approximately 3 weeks after initiation of TPN therapy with TPN-A, episodes of mental status changes of increasing duration and paroxysms were documented in five of the six patients. In one of the patients receiving TPN-C prior to TPN-A therapy, toxicity was clinically evident only 4 days after initiation of TPN-A. Serum ammonia levels were obtained and found to be elevated in the acute (ie, presenting) stage in all patients. With the discontinuance of TPN-A, ammonia levels normalized uniformly. Mental status also improved in all cases except for the patient with rapid clinical presentation who died 2 weeks after first evidence of clinical toxicity. In cases 1, 2, and 6, serum amino acid analysis in the acute phase showed reduced levels of ornithine and citrulline, the substrate and product, respectively, of condensation with carbamyl phosphate at its entry into the urea cycle. Moreover, levels of arginine, precursor to ornithine, were found to be elevated.(ABSTRACT TRUNCATED AT 250 WORDS)

Complications of essential amino acid hyperalimentation in children with acute renal failure.

The metabolic effects of intravenous hyperalimentation, using an essential amino acid (EAA) and glucose solution, were evaluated in 2 children with acute renal failure. Hyperammonemia and hyperchloremic metabolic acidosis associated with elevated plasma methionine and depressed plasma citrulline, ornithine, arginine, and histidine levels complicated the nutritional therapy. Initial infusion of a complete amino acid (CAA) solution was not associated with these aberrations and reintroduction of a CAA solution after the EAA trial resulted in a progressive amelioration of or complete recovery from these metabolic disturbances. It is likely that the hyperammonemia was due to an arginine deficiency, while excess methionine and presumably sulfate production may have contributed to the hyperchloremic metabolic acidosis in these two children.

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

The effects of diets, each with an excess of one essential amino acid, on the maintenance of pregnancy and fetal growth were investigated in rats. Rats were fed on 6% casein diet containing 5% threonine, methionine, valine, isoleucine, leucine, tyrosine, phenylalanine, tryptophan, or lysine from day 1 to day 14 or 21 of pregnancy. Excess methionine and leucine diets resulted in complete and 80% loss of fetuses, respectively. This fetal wastage was prevented by daily injection of 0.5 microgram of estrone and 4 mg of progesterone. Judging from the total food consumptions and body weight gains during pregnancy, methionine had the most severe effects, followed in order by leucine, tryptophan, valine, lysine, isoleucine, threonine, phenylalanine, and tyrosine. The weights of fetuses in the excess amino acid groups were significantly lower than those in the respective pair-fed controls. Excess aromatic amino acids caused growth retardation of fetal brain, although the levels of free tyrosine and phenylalanine in fetal brain were not high. The concentrations of free methionine and threonine were markedly elevated in the maternal plasma when these amino acids were fed in excess, but those of other amino acids were not increased appreciably by excess amounts in the diet. Changes in the maternal plasma levels of individual amino acids other than those in excess in the diet were small. On the contrary, the levels of not only the excess amino acids but also of other amino acids in fetal brains were appreciably elevated by these diets. These findings suggest that the blood-brain barrier is immature and that the synthesis of proteins in fetal brain is impaired by excess amino acids in the mothers. The importance of experiments on diets with excess of single amino acids in pregnant animals is discussed in connection with studies on inborn errors of amino acid metabolism.

Hyperammonemic encephalopathy due to essential amino acid hyperalimentation.

Hyperammonemic encephalopathy has occasionally been reported in uremic patients receiving hyperalimentation with essential amino acid (EAA) as a source of nitrogen as one of the remaining treatment options when the enteric routes were prohibited. We encountered this complication in a patient with normal renal function. A rat animal model was designed to elucidate the mechanism of hyperammonemia resulting from hyperalimentation with EAA as a source of nitrogen. Sixty-four male Long-Evan rats were divided into eight groups receiving feeds ad libitum or different formula of hyperalimentation. Hyperammonemia was found in every rat given hyperalimentation with EAA as the only nitrogen source. Using the Tukey honestly significant difference test, the results were significantly higher (p < 0.001) than that of the control group which were given feeds ad libitum and those groups given hyperalimentation for the same number of days but with mixed amino acid (MAA) as the nitrogen source. Adding arginine to EAA for a further four days after initial administration of EAA hyperalimentation for three days only slightly lowered the mean serum ammonia level. When compared to that of the three-day EAA hyperalimentation group, the difference was not statistically significant. Adding arginine, citrulline, and ornithine to EAA for a further four days significantly lowered the mean serum ammonia level. When we changed EAA hyperalimentation to MAA hyperalimentation for a further four days, the mean serum ammonia level decreased dramatically to nearly normal. Hyperalimentation using EAA as the exclusive source of nitrogen resulted in hyperammonemia. A deficiency of arginine or other amino acids of the urea cycle failed to account completely for the hyperammonemia observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth, feed intake, and plasma thyroid hormone levels in chicks fed dietary excesses of essential amino acids.

The consequences of dietary excesses of 10 essential amino acids, His, Ile, Phe, Trp, Val, Arg, Leu, Lys, Met, Thr, on growth, feed intake and plasma levels of triiodothyronine (T3) and thyroxine (T4) in growing chicks were investigated. Each amino acid was added to a starter ration to bring it to a level 2.84x above the National Research Council (1984) requirement. Excesses of all amino acids except His and Leu caused significant reductions in weight gain. Of the amino acid excesses that reduced growth, only Trp and Val did not also reduce feed intake. Gain:feed decreased significantly only in chicks consuming excess Arg, Lys, Phe, and Trp. Chicks fed excesses of Ile and Val had plasma T3 levels that were statistically higher than control levels; none of the other amino acid excesses significantly altered blood concentrations of this hormone. Compared to the control, plasma T4 levels were not significantly altered by the amino acid excesses, but there was a significant difference between Trp and Val, the latter being lower. This study shows that high dietary levels of essential amino acids cause depressions in weight gain and feed intake, and, with Ile and Val, these depressions are accompanied by elevations in plasma T3 levels. Otherwise, the amino acid excesses had little effect on plasma levels of thyroid hormones.

Unaffected arm muscle hypercatabolism in dysphagic subacute stroke patients: the effects of essential amino acid supplementation.

Alterations in muscle protein turnover of the unaffected side of stroke patients could contribute to physical disability. We investigated whether hypercatabolic activity occurred in unaffected arm muscle and whether supplemented essential amino acids (EAAs) could limit muscle hypercatabolism (MH). Thirty-eight dysphagic subacute stroke subjects (<3 months after acute event) (29 males+9 females; 69.7±11.4 yrs) were enrolled and randomized to receive 8 g/day EAAs (n=19; EAA group) or isocaloric placebo (maltodextrin; n=19, Plac group). Before randomization, all patients had their arterial (A) and venous (V) amino acids measured and muscle (A-V) differences calculated in the unaffected arm. Eight matched and healthy subjects served as controls. When compared to healthy controls, the entire stroke population showed significant muscle release (=negative value A-V) of the amino acid phenylalanine (phenyl-) indicating a prevalence of MH. Moreover, randomized EAA and Plac groups had similar rates of MH. After 38 days from the start of the protocol, the EAA group but not the Plac group had MH converted to balanced protein turnover or anabolic activity. We concluded that muscle protein metabolism of the unaffected arm of dysphagic subacute stroke individuals could be characterized by MH which can be corrected by supplemented EAAs.

[Complications due to receiving incorrect amino acid preparations]. / Complicaties door verwisseling aminozuurpreparaten.

Due to improved diagnostics and care there is an increasing number of adults with inherited metabolic diseases. The best-known example is phenylketonuria. Treatment consists of a disease-specific diet, for example protein restriction supplemented with essential amino acids. However, like prescription drugs, diet preparations can have side effects. This implies that a description of the indications and contra-indications, an assessment of the efficacy and a definition of the desired duration of treatment are required. Mistakes in the delivery of these disease-specific diet preparations by the pharmacy can have severe consequences, as illustrated by three case reports.

A "conditionally essential" nutrient, L-carnitine, as a primary suspect in endometriosis.

L-carnitine, when administered to young female mice, has been shown to induce a pathologic condition resembling human endometriosis accompanied by a marked degree of infertility. Thus, the use of this nutrient by young women may be a potential risk factor responsible for the onset of endometriosis at a later stage of their lives.