BACKGROUND:Sickle cell disorder is a haemoglobinopathy prevalent in the Vidharbha region of Maharashtra, central India. With recent evidence of oxidative stress in sickle haemoglobinopathy, a possible deficiency of antioxidant vitamins was suspected.

METHODS:We measured plasma vitamin E, vitamin C and beta-carotene levels in persons with heterozygous (n=80) and homozygous sickle cell state (n=20), and suitable healthy controls for these groups (n=100 and 66, respectively) in a community-based study in the villages near our institution.

RESULTS:Subjects with heterozygous sickle cell trait had lower vitamin E levels than their respective controls (p<0.05). Subjects with homozygous sickle cell disease had lower levels of all three vitamins (p<0.05). Vitamins E and C levels showed a significant positive correlation in both forms of sickle cell disorder.

CONCLUSION:Our findings suggest that there is depletion of the antioxidant vitamins, particularly in severe forms of sickle cell disorder. A trial of administration of therapeutic doses of vitamin E in this condition is warranted.

Autonomic function following change in posture with or without vitamin C supplementation was studied in ten (10) sickle cell anemia (SCA) and twelve (12) non-sickle cell anemia (NSCA) subjects. Arterial blood pressure and electrocardiographic measurements were taken in the supine position on a couch 80cm high and immediately on assumption of the upright position. Vitamin C was then administered orally (300mg/day for 6 weeks). At the end of the period, blood pressure and ECG measurements were again made in the supine position and in response to change in posture. Change in posture significantly decreased QRS amplitude, QRS duration, PR interval, RR interval and MABP but increased HR and rate pressure product (RPP) in both groups of subjects. The HR and RPP responses were significantly higher in NSCA than in SCA subjects (p<0.001, respectively). Vitamin C caused greater reductions in QRS duration (p<0.01), PR duration p<0.001) in the NSCA subjects than in SCA subjects. It caused, however, greater reduction in RR duration (p<0.001) and MABP in SCA subjects than in NSCA subjects. It also caused significantly greater increases in HR and RPP (p<0.001, respectively) in the SCA subjects than in NSCA subjects. After vitamin C supplementation, change in posture decreased RR interval (p<0.001), QT interval (p<0.01) and MABP (p<0.05) but increased RPP (p<0.01) in NSCA subjects. In SCA subjects, there was a fall in RR interval (p<0.001) and MABP (p<0.01), but elevated RPP (p<0.001). Changes (Delta) in MABP, HR and RPP were similar between NSCA and SCA subjects. In conclusion, these findings indicate a blunted cardiovascular autonomic response to change in posture in sickle cell anemia subjects. Chronic, oral, low-dose vitamin C supplementation equilibrates this response with those of non-sickle cell anemia subjects.

AIM:To compare pulse oximetry in children with sickle cell anaemia (SCA) and controls and test the hypothesis that vitamin C deficiency (VCD;<11.4μmol/L) is associated with nocturnal haemoglobin oxygen desaturation in SCA.

METHODS:We undertook nocturnal and daytime pulse oximetry in 23 children with SCA (median age 8 years) with known steady-state plasma vitamin C concentrations and 18 siblings (median 7 years).

RESULTS:Median nocturnal delta 12 s index (delta12 s), a measure of haemoglobin oxygen saturation (SpO(2)) variability, was 0.38 (interquartile range 0.28-0.51) in SCA and 0.35 (0.23-0.48) in controls, with 9/23 and 6/18, respectively, having a delta12 s>0.4, compatible with obstructive sleep apnoea (OSA). Eleven of twenty-three with SCA had VCD; logged vitamin C concentrations showed a 66% decrease per 0.1 unit increase in delta12 s ([95% CI -86%, -15%]; p=0.023) and delta12 s>0.4 was associated with VCD (odds ratio 8.75 [1.24-61.7], p=0.029). Daytime and mean nocturnal SpO(2) were lower in SCA but there was no association with vitamin C.

CONCLUSION:Obstructive sleep apnoea (OSA), detected from nocturnal haemoglobin oxygen saturation variability, is common in Tanzanian children and associated with vitamin C Deficiency in SCA. The direction of causality could be determined by comparing OSA treatment with vitamin C supplementation.

A certain population of red blood cells in patients with sickle cell anemia has an elevated density and possesses an abnormal membrane. These"dense cells"have a tendency to adhere to neutrophils, platelets, and vascular endothelial cells, and, thus, they could trigger vasoocclusion and the subsequent painful crisis from which these patients suffer. We developed a laboratory method of preparing such dense cells and found that nutritional antioxidant supplements, hydroxyl radical scavengers, and iron-binding agents could inhibit the formation of dense cells in vitro. The concentrations at which effective nutritional supplements could inhibit dense cell formation by 50% were 4.0 mg/mL for aged garlic extract, 0.38 mg/mL for black tea extract, 0.13 mg/mL for green tea extract, 0.07 mg/mL for Pycnogenol, 930 microM for alpha-lipoic acid, 270 microM for vitamin E, 45 microM for coenzyme Q(10), and 32 microM for beta-carotene. Both an ex vivo study and a pilot clinical trial demonstrated that a cocktail consisting of daily doses of 6 g of aged garlic extract, 4-6 g of vitamin C, and 800 to 1200 IU of vitamin E may indeed be beneficial to the patients.

This study seeks to examine the effects of vitamin C supplementation or/and warmth on forearm blood flow (FBF) and forearm vascular resistance (FVR) in sickle cell anaemia (SCA) subjects in the steady state. Sixteen (16) SCA subjects of both sexes (mean age, 23.4+/-1.5 yrs.) were studied. Blood pressure (BP, mm Hg) and FBF (ml/min) measurements were made at rest, with warmth stimulation, after vitamin C supplementation for 6 weeks at 300 mg per day and with warmth stimulation after vitamin C supplementation. Warmth stimulation was induced by immersing the left foot in a bowl of water at a temperature of 40 degrees C for 2 minutes. Forearm blood flow (FBF) [corrected] was measured by means of a forearm plethysmograph. Forearm vascular resistance (FVR, arbitrary units) was calculated by dividing mean arterial pressure (MAP) with FBF. Warmth stimulation at 40 C significantly decreased systolic blood pressure (SBP) (p<0.05), diastolic blood pressure (DBP) (p<0.01), MAP (p<0.01) and FVR (p<0.01) but significantly increased FBF (p<0.01). Vitamin C supplementation also significantly reduced SBP (p<0.001), DBP (p<0.01), MAP (p<0.01) and FVR (p<0.05) but significantly increased FBF (p<0.01). After vitamin C supplementation, warmth stimulation potentiated the reduction in SBP (p<0.001), DBP (p<0.01), FVR (p<0.01) and increase in FBF (p<0.01). In conclusion, warmth stimulation at 40 [corrected] degrees C or vitamin C supplementation caused a decrease in arterial blood pressure, forearm vascular resistance and increase in forearm blood flow in sickle cell anaemia subjects. Pretreatment with vitamin C enhanced the vasodilator effect of warmth.

This study seeks to examine the effects of vitamin C supplementation or/and warmth on forearm blood flow (FBF) and forearm vascular resistance (FVR) in sickle cell anaemia (SCA) subjects in the steady state. Sixteen (16) SCA subjects of both sexes (mean age, 23.4+/-1.5 yrs.) were studied. Blood pressure (BP, mm Hg) and FBF (ml/min) measurements were made at rest, with warmth stimulation, after vitamin C supplementation for 6 weeks at 300 mg per day and with warmth stimulation after vitamin C supplementation. Warmth stimulation was induced by immersing the left foot in a bowl of water at a temperature of 40 degrees C for 2 minutes. Forearm blood flow (FBF) [corrected] was measured by means of a forearm plethysmograph. Forearm vascular resistance (FVR, arbitrary units) was calculated by dividing mean arterial pressure (MAP) with FBF. Warmth stimulation at 40 C significantly decreased systolic blood pressure (SBP) (p<0.05), diastolic blood pressure (DBP) (p<0.01), MAP (p<0.01) and FVR (p<0.01) but significantly increased FBF (p<0.01). Vitamin C supplementation also significantly reduced SBP (p<0.001), DBP (p<0.01), MAP (p<0.01) and FVR (p<0.05) but significantly increased FBF (p<0.01). After vitamin C supplementation, warmth stimulation potentiated the reduction in SBP (p<0.001), DBP (p<0.01), FVR (p<0.01) and increase in FBF (p<0.01). In conclusion, warmth stimulation at 40 [corrected] degrees C or vitamin C supplementation caused a decrease in arterial blood pressure, forearm vascular resistance and increase in forearm blood flow in sickle cell anaemia subjects. Pretreatment with vitamin C enhanced the vasodilator effect of warmth.

The effects of warmth stimulation and/or supplementation with vitamin E (300 mg/day for 6 weeks) on forearm blood flow (FBF) and forearm vascular resistance (FVR) were measured in 8 sickle cell anaemia (SCA) (mean age = 22.8 + 0.8 years) and 11 non sickle cell anaemia (NSCA) subjects (mean age = 23.2 + 1.1 years) of both sexes. Warmth stimulation was induced by immersing the left foot in warm water at 400C for 2 minutes. Forearm blood flow was measured with the venous occlusion plethysmography method. Warmth increased FBF (p<0.01 in each group) and reduced FVR (p<0.05) in NSCA subjects. The change in FBF was greater (p<0.05) in the NSCA subjects than in the SCA subjects. Supplementation with vitamin E reduced systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP) (p<0.001 in each case) in the NSCA subjects but had little or no effect on the SCA subjects. Vitamin E increased FBF in NSCA subjects (p<0.05) and SCA subjects (p<0.01) and decreased FVR in both groups (p<0.05 in NSCA and p<0.01 in SCA subjects). The change in FVR seen in the NSCA subjects was less (p<0.01) than the change in SCA subjects. After supplementation with vitamin E, warmth further decreased SBP (p<0.01 in each group) and FVR (p<0.01 in each case) and increased FBF in both groups (p<0.01 respectively). The changes caused by warmth after vitamin E supplementation on the blood pressure parameters, FBF and FVR were similar in the two groups of subjects.