Red Blood Cell Choline Research Articles

Unfavorable effect of type 1 and type 2 diabetes on maternal and fetal essential fatty acid status: a potential marker of fetal insulin resistance

Pregestational maternal diabetes increases obesity and diabetes risks in the offspring. Both conditions are characterized by insulin resistance, and diabetes is associated with low membrane arachidonic (AA) and docosahexaenoic (DHA) acids. We investigated whether type 1 and type 2 diabetes in pregnancy compromise maternal and fetal membrane essential fatty acids (FAs). We studied 39 nondiabetic (control subjects), 32 type 1 diabetic, and 17 type 2 diabetic pregnant women and the infants they delivered. Maternal and cord blood samples were obtained at midgestation and at delivery, respectively. Plasma triacylglycerols and choline phosphoglycerides and red blood cell (RBC) choline and ethanolamine phosphoglyceride FAs were assessed. The difference in maternal plasma triacylglycerol FAs between groups was not significant. However, the type 1 diabetes group had lower plasma choline phosphoglyceride DHA (3.7 +/- 0.9%; P < 0.01) than did the control group (5.2 +/- 1.6%). Likewise, RBC DHA was lower in the type 1 [choline: 3.4 +/- 1.5% (P < 0.01); ethanolamine: 5.9 +/- 2.5% (P < 0.05)] and type 2 [choline: 3.5 +/- 1.6% (P < 0.05)] diabetes groups than in the control group (choline: 5.5 +/- 2.2%; ethanolamine: 7.5 +/- 2.5%). Cord AA and DHA were lower in the plasma (type 1: P < 0.01) and RBC (type 2: P < 0.05) choline phosphoglycerides of the diabetics than of the control subjects, and cord RBC ethanolamine phosphoglycerides were lower in DHA (P < 0.05) in both diabetes groups than in the control group. Diabetes (either type) compromises maternal RBC DHA and cord plasma and RBC AA and DHA. The association of these 2 FAs with insulin sensitivity may mean that the current finding explains the higher incidence of insulin resistance and diabetes in the offspring of diabetic women.

Differences in red blood cell choline and lipid-bound choline between patients with Alzheimer disease and control subjects

The concentrations of red blood cell choline, glycerophosphocholine, phosphocholine and lipid-bound choline were measured in patients with Alzheimer disease (AD) and in normal elderly controls. Red blood cell choline in the Alzheimer group (41.4±9.2 nmol/ml) was significantly higher ( p<0.023) than in the elderly controls (17.7±2.3 nmol/ml). Red blood cell lipid-bound choline (1387±58 nmol/ml) in the AD group was significantly lower ( p<0.0022) than in the age-matched controls (1667±65), while there were no significant differences in glycerophosphocholine or phosphocholine. Plasma choline and lipid-bound choline did not differ significantly between the groups. The mechanisms for these changes still need further study, although the finding of decreased lipid-bound choline supports the concept of altered phospholipid metabolism in patients with AD.

Changes in red blood cell choline and choline-bound lipids with oral lithium

The influence of oral lithium on the concentration of red blood cell choline (Ch), lecithin, glycerophosphorylcholine (GPCh) and phosphorylcholine (PCh) was studied. The concentration of RBC Ch was significantly elevated and the concentration of lecithin, GPCh and PCh significantly depressed in 16 patients on oral lithium compared to 9 age-matched controls. We conclude that lithium markedly depletes the red blood cell of choline containing compounds including lecithin. These changes may be responsible for both the therapeutic efficacy and the toxicity of lithium.

Red cell choline in spasmodic torticollis and in a monozygotic twin pair with Tourette's syndrome

1. 1. Alterations in cholinergic function may play a role in the pathophysiology of idiopathic spasmodic torticollis (ST) and Gilles de la Tourette's syndrome (GTS). We measured red blood cell (RBC) choline in (i) ST ( n = 24) and paired controls matched for age and gender (ii) a 20-year old pair of monozygotic twins with GTS, one of whom was moderately affected (CV) and the other virtually recovered (DV) (iii) both parents of the GTS twins, using gas chromatography — mass spectometry 2. 2. RBC choline decreased with age in control men (r = −0.76: p <0.01) but not in control women. 3. 3. RBC choline (nmol/ml) was higher in control men (18.3 ± 4.8, X ± SD) vs control women (13.1 ± 4.3) (p = 0.025). 4. 4. There was no significant difference in RBC choline (nmol/ml) between ST patients (16.6 ± 5.0) and controls (15.5 ± 5.2). 5. 5. The RBC choline values (nmol/ml) in the twins and parents were: 56.6 (CV), 58.3 (DV), 89.8 (father), 38.3 (mother) and in the controls (age 20–24) (n = 5) 18.2 ± 3.6. 6. 6. These data suggest (i) RBC choline is affected by age and gender (ii) RBC choline is unchanged In ST (iii) the regulation of RBC choline is under genetic control (iv) elevated RBC choline is not a state marker for GTS.

RBC and plasma choline in neuroleptic-treated schizophrenic patients

We measured red blood cell (RBC) choline and plasma choline concentrations in 27 chronic schizophrenic inpatients and 23 normal controls. Both blood choline measures had a significant test-retest reliability in patients whose neuroleptic status remained unchanged over 1 month. RBC choline concentration was significantly lower in patients medicated with neuroleptics and cogentin. Patients with a low RBC choline and a low RBC/plasma choline ration were on significantly higher doses of medication and had higher scores on the hostility/suspiciousness subscale of the Brief Psychiatric Rating Scale. RBC choline increased when neuroleptics were discontinued. Blood choline measures were also compared among medication-free schizophrenic patients, inpatients with other diagnoses, and normal controls. No significant differences were seen among these groups for any choline measure, although the schizophrenic patients showed greater variability. Medication-free schizophrenic patients with such clinical factors as tardive dyskinesia and abnormalities on computed tomography contributed to this variability. Age was positively correlated with plasma choline.

Red blood cell/plasma choline ratio in elderly depressed and demented patients

In further study of red blood cell (RBC) and plasma choline concentrations in 160 elderly subjects, we found no significant differences in RBC/plasma choline ratios among depressed, demented, and healthy subjects. On the basis of a smaller sample, we had earlier reported that a significantly higher proportion of Alzheimer patients had RBC/plasma choline ratios >62;1.9. Thus, it now appears that static RBC choline levels cannot be recommended as a specific marker of Alzheimer's dementia. However, within subgroups of these diagnostic categories, determined by RBC/plasma choline ratios ⩽1.9 or >62;1.9, consistent differences in electroencephalographic (EEG) sleep measures were found. The subgroup of demented patients with a RBC/plasma choline ratio >62;1.9 was more impaired on the Blessed Dementia Rating Scale and had less rapid eye movement (REM) sleep than the subgroup with a choline ratio ⩽1.9. Similarly, depressives with a choline ratio ⩽1.9 had a lower REM latency than depressives with a choline ratio >62;1.9. Finally, depressed-demented (i.e., mixed-symptom) patients with a choline ratio >62;1.9 showed less sleep continuity disturbance but more indeterminate non-REM sleep (reflecting loss of spindles and K-complexes) than those with lower choline ratios. These differences parallel those previously reported for diagnostically “pure” depressed and demented patients, and they suggest a possible link between peripheral RBC/plasma choline measures and central nervous system function as reflected in sleep physiological alterations.

Human red blood cell choline uptake with age and Alzheimer's disease

Since previous studies suggested that blood choline homeostasis is altered in aging and in Alzheimer's disease, choline uptake was examined in human red blood cells (RBC) from young adults, intellectually-intact elderly controls and outpatients with Alzheimer's disease. Eadie-Hofstee analysis of uptake by RBC from young controls indicated two components; thus, group comparisons were done with 1 and 50 μM choline in the media. Temperature-dependent choline uptake at low and high choline concentrations increased in RBC from elderly controls (62–66%) or Alzheimer patients (52–54%) compared to young controls. These changes in transport were not directly related to altered RBC choline content, since RBC choline concentrations did not vary significantly between groups. However, plasma choline content was significantly elevated in elderly controls and Alzheimer patients compared to young control values. The RBC to plasma ratio of choline was reduced in elderly compared to young controls, whereas the ratio in Alzheimer patients was between the two other groups. Thus, abnormalities in RBC choline uptake and plasma choline content were not exacerbated in Alzheimer patients, and these results do not support suggestions that Alzheimer's disease is a form of generalized accelerated aging. The striking changes in RBC choline uptake and plasma choline content in elderly subjects do indicate age-related changes in systemic choline homeostasis and these abnormalities may contribute to the predisposition of the elderly to neurological diseases.

NMR chemistry analysis of red blood cell constituents in normal subjects and lithium-treated psychiatric patients

Red blood cells from 18 lithium carbonate-treated patients with bipolar affective disorder and 12 normal volunteers were analyzed using 1H-nuclear magnetic resonance (NMR) spectroscopy. The spectra were analyzed for alanine, adenosine triphosphate (ATP), choline, 2,3-diphosphoglycerol, glucose, glutathione, glycine, and lactate. Significant elevations of choline and lactate were found in the lithium-treated patients compared with normal, unmedicated subjects. The elevation of lactate due to anaerobic metabolism in the red blood cells was further investigated via fluoremetric analysis and appears to be caused by blood standing at room temperature. The observed increases in red blood cell choline are sufficiently high and statistically significant to warrant additional studies on the dramatic effects of lithium on this red cell metabolite, which might be important for an understanding of its mechanism of action in psychiatric disorders.

Lack of clinically significant improvement of patients with tardive dyskinesia following phosphatidylcholine therapy

A double-blind controlled study was undertaken to examine the value of phosphatidylcholine as a treatment for tardive dyskinesia (TD) in 19 psychiatric patients. All patients were maintained on their usual psychotropic medication throughout the entire study. In addition, they were given either phosphatidylcholine (30 g/day) or placebo for 6 weeks. Thirteen of the patients received the crossover treatment for 6 weeks, after which 10 of the 13 were continued on the crossover medication for an additional 6 weeks. At the end of the study, 5 patients had received phosphatidylcholine for 12 weeks and another 12 patients had received the drug for only 6 weeks. Plasma and red blood cell choline levels were monitored every 3 weeks as a measure of compliance. Although some patients showed clinical improvement of their TD, the results did not differ significantly between active drug and placebo. This was in spite of a marked elevation of plasma and red blood cell choline (up to 300% for the Lafayette Clinic patients and up to 400% for the patients from the Ypsilanti Regional Psychiatric Hospital) during treatment with phosphatidylcholine. Side effects of the drug included occasional gastrointestinal upsets and diarrhea but, in general, the medication was tolerated very well. The results indicate that large doses of phosphatidylcholine of soya origin are of no clinical value in treating symptoms of TD in spite of very large increases in blood choline.

Blood choline and response to clonazepam and haloperidol in Tourette's syndrome.

This paper reports the results of a single blind clinical study of drug treatment response of 20 patients with Tourette's syndrome to haloperidol and clonazepam. Because patients with Tourette's syndrome have been reported to have increased red blood cell choline levels, choline levels were examined in relation to treatment response. Differential drug treatment response was found among patients with high versus low red blood cell-to-plasma choline ratios. Patients with high red blood cell-to-plasma choline ratios responded better to clonazepam than to haloperidol. This suggests that there may be two distinct subtypes of patients with Tourette's syndrome.

Red blood cell choline. I: Choline in Alzheimer's disease

Seventeen drug-free patients with Alzheimer's disease (AD) and 15 normal elderly controls of which 13 age- and sex-matched pairs were included, participated in a study of red blood cell (RBC) and plasma choline. Mean values for RBC choline, plasma choline, and the ratio of RBC/plasma choline did not differ between the AD and control groups. Degree of dementia did not correlate with any blood choline measure. A correlation was found between age and RBC choline ( r = 0.57; p ⩽ 0.01) and the RBC/plasma choline ration ( r = 0.56; p ⩽ 0.03) in normals, but not in AD patients. RBC choline correlated with plasma choline in AD patients only ( r = 0.46; p ⩽ 0.03). These results do not support the use of RBC and plasma choline concentrations as either a diagnostic tool to identify AD patients or an antermortem index of the cholinergic deficit in brains of patients with Alzheimer's disease.

Red blood cell choline. II: Kinetics in alzheimer's disease

The kinetic parameters of choline uptake into red blood cells from patients with Alzheimer's disease and normal elderly controls were compared. The K d and V max values for choline uptake into red cells were determined based on a kinetic analysis of choline uptake at six different concentrations of labeled extracellular choline. The theoretical choline uptake, representing the initial rate of choline influx into choline-depleted red cells given the plasma choline concentration and the kinetic parameters of choline uptake, was also calculated. Alzheimer's disease patients and normal controls did not differ in any kinetic parameter of choline uptake. K d and V max values for red cell choline uptake were strongly correlated among normal controls, but not among patients with Alzheimer's disease. In addition, among the patients with Alzheimer's disease, the theoretical choline uptake was strongly correlated with the severity of dementia. The possible significance of these findings in relation to altered choline metabolism in Alzheimer's disease is discussed.

Red cell choline in Korsakoff psychosis

1. Red blood cell (RBC) choline was measured in 48 male patients with Korsakoff psychosis secondary to alcoholism and in 19 age-matched male controls using gas chromatographymass spectrometry. 2. The variance in RBC choline was significantly different between Korsakoff patients and controls (p < 0.002). 3. RBC choline was significantly higher in Korsakoff patients compared with controls (p < 0.02). 4. There was no significant correlation between age and RBC choline. 5. Higher RBC choline levels suggest differences in membrane transport properties. Differences in membrane properties may indicate a neuronal membrane vulnerability to the toxic effect of alcohol or to thiamine deficiency which lead to the degenerative changes associated with Korsakoff psychosis.

Lithium, red blood cell choline and clinical state: A prospective study in manic-depressive patients

Red blood cell (RBC) choline and ergothioneine levels were measured after repeated sampling of bipolar manic-depressive patients over 11 months of lithium maintenance. In addition, blood levels were measured in healthy volunteers, newly hospitalised lithium-free patients and from patients prior to, and after, initiating lithium. RBC choline levels did not differ between normal volunteers and newly admitted lithium-free patients with either mania or depression. After 4 weeks of lithium treatment RBC choline levels increased 6-fold, whereas the levels of the closely related compound ergothioneine did not change. Significant changes in mood during lithium maintenance were not accompanied by changes in RBC choline levels. These data indicate that lithium produced a specific accumulation of choline in erythrocytes. However the increased levels appear to be unrelated to clinical state and do not distinguish lithium responders from non-responders.

Effects on red blood cell choline transport induced by different sulfhydryl compounds.

The uptake of choline was studied in different types of paroxysmal nocturnal hemoglobinuria (PNH)-like RBC obtained from normal human erythrocytes by the action of different sulfhydryl compounds. The results were compared with the uptake of choline in true PNH cells and in normal reticulocytes. The PNH-like cells which better mimicked true PNH were those prepared using acetylcysteine. Indeed these erythrocytes displayed a capacity to incorporate choline against a concentration gradient exactly as PNH cells exposed to either acetylcholine or choline. The uptake of choline by by the other PNH-like cells differed from that of PNH erythrocytes in several ways. The results suggest that every sulfhydryl compound induces a different damage on RBC membrane.

Levels of red blood cell choline after discontinuation of lithium therapy

Levels of red blood cell choline after discontinuation of lithium therapy

RBC and plasma choline levels in control and depressed individuals: A critical evaluation

Red blood cell (RBC) and plasma choline (Ch) were measured in 78 depressed, drug-free patients and in 23 normal, drug-free control subjects. RBC Ch levels displayed a huge variability among the patients, in contrast to those measured in normal controls. Plasma Ch levels, on the other hand, were more consistent within each group, and were correlated with age among the two populations studied. RBC Ch levels would appear to be independent of plasma Ch levels, and to be highly individualized and reproducible within each subject. A segment of the depressed population exhibited significantly higher RBC Ch levels than those seen in the normal control population. A clinical correlation of RBC and plasma Ch levels within the depressed population indicated that the patients with RBC Ch levels exceeding 35 nmole/ml might represent a diagnostically distinct subpopulation with specific clinical characteristics. Results presented here, although preliminary, suggest a role for RBC Ch as a biological marker in certain categories of depressive illness.

Ribosediphosphate in the human erythrocyte

Red blood cells from 18 lithium carbonate-treated patients with bipolar affective disorder and 12 normal volunteers were analyzed using 1H-nuclear magnetic resonance (NMR) spectroscopy. The spectra were analyzed for alanine, adenosine triphosphate (ATP), choline, 2,3-diphosphoglycerol, glucose, glutathione, glycine, and lactate. Significant elevations of choline and lactate were found in the lithium-treated patients compared with normal, unmedicated subjects. The elevation of lactate due to anaerobic metabolism in the red blood cells was further investigated via fluoremetric analysis and appears to be caused by blood standing at room temperature. The observed increases in red blood cell choline are sufficiently high and statistically significant to warrant additional studies on the dramatic effects of lithium on this red cell metabolite, which might be important for an understanding of its mechanism of action in psychiatric disorders.