Novel relationships between B12, folate and markers of inflammation, oxidative stress and NAD(H) levels, systemically and in the CNS of a healthy human cohort.

OBJECTIVE: To evaluate the relationship between folate, cobalamin (Cbl), and homocysteine (Hcy), and markers of inflammation and oxidative stress within the periphery and central nervous system (CNS) of a healthy human cohort. METHODS: Thirty-five matched cerebrospinal fluid (CSF) and plasma samples were collected from consenting participants who required a spinal tap for the administration of anaesthetic. Plasma concentrations of Hcy and both plasma and CSF levels of folate, Cbl, nicotinamide adenine dinucleotide (NAD(H)) and markers of inflammation (interleukin-6, IL-6), and oxidative stress (F2-isoprostanes, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and total antioxidant capacity (TAC)) were quantified. RESULTS: In the peripheral circulation, positive associations were observed between plasma folate and Cbl, and plasma TAC (P ≤ 0.01; P ≤ 0.01) and plasma NAD(H) (P ≤ 0.05; P ≤ 0.05) levels, respectively. Plasma folate was inversely associated with plasma Hcy concentrations (P ≤ 0.05); however, no statistically significant relationships were observed between plasma Hcy and plasma markers of inflammation, oxidative stress, or [NAD(H)]. Within the CNS plasma Hcy correlated positively with CSF IL-6 (P ≤ 0.01) and negatively with CSF NAD(H) (P ≤ 0.05) concentrations. An inverse association was observed between CSF folate and CSF levels of IL-6 (P ≤ 0.05). Unexpectedly, a positive association between CSF Cbl and CSF 8-OHdG levels was also found (P ≤ 0.01). DISCUSSION: These results indicate that folate and Cbl concentrations may influence the levels of oxidative damage, inflammation, and NAD(H), both systemically and within the CNS.

Effect of umbilical cord blood prefreeze variables on postthaw viability.

BACKGROUND: Assessment of the overall postthaw (PT) viability of an umbilical cord blood (UCB) unit is an important criterion for determining the quality of the unit for transplantation. Overall PT viability is a measure of cellular damage that can occur to the UCB during collection, storage, processing, freezing, and thawing. STUDY DESIGN AND METHODS: This study investigated factors measured before freezing of the UCB that could affect overall PT viability of the stem cell unit from 257 collected cord blood samples. The analysis included hematologic variables, cord blood collection characteristics, and stem cell separation and preservation factors. RESULTS: Each of the variables, postprocess (PP) neutrophils (%), PP hematocrit, overall PP viability (%), freeze rate (°C/min), and time from collection to freezing (hr) were shown to contribute to overall PT viability. Each UCB sample was given a calculated "viability prediction" (VP) score based on the influence or impact of each of these variables. This score was compared to the measured PT viability. Variables with a low VP score had correspondingly low PT viability, indicating more overall damage to the cells. The results showed that the higher the VP score, the higher the PT viability. CONCLUSION: These findings provide a framework for identifying those units that are most likely to have a high overall PT viability and hence an increased likelihood of successful engraftment of the CB-sourced stem cells. The VP score could aid in the selection of a donor cord blood unit for transplantation.

Effect of maternal iron status on the number of CD34+ stem cells harvested from umbilical cord blood.

BACKGROUND: Hematopoietic progenitor cells (HPCs) from umbilical cord blood (UCB) are an alternative source of stem cells. However an adequate number of HPCs must be harvested from each UCB sample to make therapeutic applications possible. This study investigated the impact of selected maternal indices (in particular iron status) on the number of CD34+ cells collected in the UCB. STUDY DESIGN AND METHODS: Blood samples were collected from 91 matched mother and umbilical cord pairs and analyzed for full blood count, iron status, and C-reactive protein. Viable CD34 enumeration was performed on the cord blood samples. RESULTS: Low CD34+ cell counts were associated with higher maternal serum ferritin (SF), older mothers, lower UCB white blood cell count (WCC), lower UCB nucleated red blood cells (NRBCs), and lower birthweight. Maternal SF correlated with maternal variables of iron status and RBC indices, newborn weight, placental weight, and NRBCs/100 WCC. CONCLUSION: This study indicates that lower numbers of CD34+ cells are more likely to occur when collected from mothers with higher SF. This finding suggests that maternal SF and associated iron status play a significant, but as yet undefined, role in the generation of CD34+ cells in UCB.

Dietary factors influence production of the soy isoflavone metabolite s-(-)equol in healthy adults.

S-(-)equol, an intestinally derived metabolite of the soy isoflavone daidzein, is proposed to enhance the efficacy of soy diets. Adults differ in their ability to produce equol when consuming soy foods for reasons that remain unclear. Therefore, we performed a comprehensive dietary analysis of 143 macro- and micronutrients in 159 healthy adults in the United States (n = 89) and Australia (n = 70) to determine whether the intake of specific nutrients favors equol production. Three-d diet records were collected and analyzed using Nutrition Data System for Research software and S-(-)equol was measured in urine by mass spectrometry. Additionally, in a subset of equol producers and nonproducers (n = 10/group), we examined the long-term stability of equol producer status by retesting 12, 18, and 24 mo later. Finally, the effect of oral administration of the antibiotic metronidazole (500 mg/d for 7 d) on equol production was examined in 5 adults monitored during a 4-mo follow-up period. Equol producers accounted for 30.3% and 28.6% of the United States and Australian participants, respectively (overall frequency, 29.6%). No significant differences were observed for total protein, carbohydrate, fat, saturated fat, or fiber intakes between equol producers and nonproducers. However, principal component analysis revealed differences in several nutrients, including higher intakes of polyunsaturated fatty acids (P = 0.039), maltose (P = 0.02), and vitamins A (P = 0.01) and E (P = 0.035) and a lower intake of total cholesterol (P = 0.010) in equol producers. During a 2-y period, equol producer status remained unchanged in all nonproducers and in 80% of equol producers, whereas metronidazole abolished equol production in only 20% of participants. In conclusion, these findings suggest that major differences in the macronutrient content of the diet appear not to influence equol production, but subtle differences in some nutrients may influence the ability to produce equol, which was a relatively stable phenomenon.

Vitamin B12 and vegetarian diets.

Vitamin B12 is found almost exclusively in animal-based foods and is therefore a nutrient of potential concern for those following a vegetarian or vegan diet. Vegans, and anyone who significantly limits intake of animal-based foods, require vitamin B12-fortified foods or supplements. Vitamin B12 deficiency has several stages and may be present even if a person does not have anaemia. Anyone following a vegan or vegetarian diet should have their vitamin B12 status regularly assessed to identify a potential problem. A useful process for assessing vitamin B12 status in clinical practice is the combination of taking a diet history, testing serum vitamin B12 level and testing homocysteine, holotranscobalamin II or methylmalonic acid serum levels. Pregnant and lactating vegan or vegetarian women should ensure an adequate intake of vitamin B12 to provide for their developing baby. In people who can absorb vitamin B12, small amounts (in line with the recommended dietary intake) and frequent (daily) doses appear to be more effective than infrequent large doses, including intramuscular injections. Fortification of a wider range of foods products with vitamin B12, particularly foods commonly consumed by vegetarians, is likely to be beneficial, and the feasibility of this should be explored by relevant food authorities.

Predicting overall viability of cord blood harvests.

BACKGROUND: Cord blood (CB) is a product rich in primitive adult stem cells used in hematopoietic stem cell transplantation. After collection, the CB is transported to a facility where the unit is processed and then frozen up to 48 hours later. These processes can lead to compromised white blood cell (WBC) viability. This study investigates the factors that affect WBC viability before freezing of the cells. STUDY DESIGN AND METHODS: We retrospectively analyzed WBC viability from 9918 CB collections harvested from 2003 to 2010 to determine if collection volume and time to freezing (TTF) had a significant effect on WBC viability. CB was collected in dispersed clinical locations by local staff trained to the same methods. CB was transported to the central lab under controlled conditions for analysis and processing. RESULTS: The collected CB units had a mean volume of 77.1 ± 31.3 mL, mean WBC count of 10.5 × 10(8) ± 5.6 × 10(8) , mean total CD34+ cell count of 4.0 × 10(6) ± 3.7 × 10(6) , and mean WBC viability of 91.7% ± 6.5%. WBC viability was most significantly affected by the volume of CB collected and the TTF. As collection volumes increased, WBC viability increased, with mean viability of 95.0% ± 3.5% in CB collections of more than 120 mL. Decreased viability was associated with volumes of less than 60 mL and TTF of more than 24 hours. From these data we have developed decision tables that estimate WBC viability based on CB volume and TTF. CONCLUSION: This study identifies optimal TTF for different collection volumes to maintain WBC viability of the collected CB.

The relative impact of a vegetable-rich diet on key markers of health in a cohort of Australian adolescents.

Childhood obesity is a widespread health problem in Australia. Overweight in childhood can lead to adult overweight and the development of risk factors for cardiovascular disease (CVD). Effective strategies for reducing childhood obesity are urgently required. A vegetarian diet has been shown to be an effective prophylactic to many lifestyle diseases in the adult population and may therefore be beneficial in children. However the metabolic demands of adolescents are different to adults and the impact of a vegetarian diet on CVD markers in this demographic is not certain. We compared key physiological and biochemical markers of health against responses to a modified, Schools Physical Activity and Nutrition Survey (SPANS) using one-way and two-way Analysis of Variance. 215 adolescents (14-15 yrs) from 5 Adventist secondary schools in the Sydney and Hunter regions of New South Wales, Australia, participated in this study. Adolescents consuming predominantly vegetarian foods showed significantly better scores on markers of cardiovascular health, including, body mass index (BMI), waist circumference, Cholesterol/High density lipoprotein ratio and low density lipoprotein. Adolescents consuming nuts more than once per week, also showed lower scores for BMI and serum glucose irrespective of their vegetarian status. Markers of general health including haemoglobin and average height were not different between groups; however a lower serum level of vitamin B12 was apparent in the vegetarian cohort. Surprisingly, exercise on its own was not statistically associated with any of the risk factors tested suggesting that diet may be the most significant factor in promoting health in this age group.

Macrocytosis--an Australian general practice perspective.

BACKGROUND: Clinicians' approaches to identifying and investigating red blood cell macrocytosis are variable. There is little literature on the Australian primary care approach. METHODS: Mean corpuscular volume (MCV) in blood counts from an urban Australian general practice were calculated and general practitioners in the surrounding division were surveyed on their experience of and approach to investigating macrocytosis. RESULTS: Mean corpuscular volume above 100 fL was found in 1.7% of patients, and 7.3% had an MCV above 96 fL. Ninety-four percent of responding GPs replied they would further investigate this clinical finding, particularly at levels above 100 fL. Alcohol excess and vitamin B12 deficiency were the most common single causes of macrocytosis in their experience. DISCUSSION: Macrocytosis can be a marker for disease and it is important to identify and investigate its presence. Further research is needed to clarify the reference range for healthy adults in general practice and to formulate evidence based clinical guidelines for investigating isolated macrocytosis.

Analysis of the cobalt content in Australian foods.

The cobalt content of Australian foods is unknown, and as this content is, at least in part, related to the respective concentrations in the Australian soil, data collected previously in other countries may not reflect the levels in Australian produce. To compare reported food cobalt levels to that found in Australian foods, one hundred and fifty different food and beverage items from each of the major food groups were selected for analysis, based on annual sales figures in Australia. Food digests were analysed for cobalt content using a Finnigan High Resolution Inductively Coupled Plasma Mass Spectrometer. While some variation in cobalt content was seen in a small selection of foods from different States, in general terms, the cobalt content of Australian foods is similar to that seen in data from other countries.

Comparison of the dietary cobalt intake in three different Australian diets.

Differences in the dietary intake of cobalt were assessed for vegans, lacto-ovo-vegetarian and non-vegetarian Australians using food intake logs, and daily or average trend recall over three months. A significant decrease in cobalt intake was observed for the lacto-ovo-vegetarian population compared with the intake in vegans and omnivores. There is no RDI for cobalt, however, the cobalt intake of Australians was similar to that reported in other countries. Microflora above the terminal ileum have been shown to produce significant amounts of biologically available vitamin B12. This study was unable to demonstrate a correlation between elemental cobalt intake and serum vitamin B12 concentrations in humans, as has been shown in vitro.