Building knowledge, optimising physical and mental health and setting up healthier life trajectories in South African women (Bukhali): a preconception randomised control trial part of the Healthy Life Trajectories Initiative (HeLTI).

INTRODUCTION: South Africa's evolving burden of disease is challenging due to a persistent infectious disease, burgeoning obesity, most notably among women and rising rates of non-communicable diseases (NCDs). With two thirds of women presenting at their first antenatal visit either overweight or obese in urban South Africa (SA), the preconception period is an opportunity to optimise health and offset transgenerational risk of both obesity and NCDs. METHODS AND ANALYSIS: Bukhali is the first individual randomised controlled trial in Africa to test the efficacy of a complex continuum of care intervention and forms part of the Healthy Life Trajectories Initiative (HeLTI) consortium implementing harmonised trials in Canada, China, India and SA. Starting preconception and continuing through pregnancy, infancy and childhood, the intervention is designed to improve nutrition, physical and mental health and health behaviours of South African women to offset obesity-risk (adiposity) in their offspring. Women aged 18-28 years (n=6800) will be recruited from Soweto, an urban-poor area of Johannesburg. The primary outcome is dual-energy X-ray absorptiometry derived fat mass index (fat mass divided by height2) in the offspring at age 5 years. Community health workers will deliver the intervention randomly to half the cohort by providing health literacy material, dispensing a multimicronutrient supplement, providing health services and feedback, and facilitating behaviour change support sessions to optimise: (1) nutrition, (2) physical and mental health and (3) lay the foundations for healthier pregnancies and early child development. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Human Ethics Research Committee University of the Witwatersrand, Johannesburg, South Africa (M1811111), the University of Toronto, Canada (19-0066-E) and the WHO Ethics Committee (ERC.0003328). Data and biological sample sharing policies are consistent with the governance policy of the HeLTI Consortium (https://helti.org) and South African government legislation (POPIA). The recruitment and research team will obtain informed consent. TRIAL REGISTRATION: This trial is registered with the Pan African Clinical Trials Registry (https://pactr.samrc.ac.za) on 25 March 2019 (identifier: PACTR201903750173871). PROTOCOL VERSION: 20 March 2022 (version #4). Any protocol amendments will be communicated to investigators, Institutional Review Board (IRB)s, trial participants and trial registries.

Comparison of dietary and plasma phospholipid fatty acids between normal weight and overweight black South Africans according to metabolic health: The PURE study.

BACKGROUND: Information regarding circulating fatty acids (FA) in association with metabolic health in black Africans is scarce, while the usefulness of circulating FAs as biomarkers of dietary fat intake and predictors for medical conditions is increasing. OBJECTIVE: We compared eleven dietary and the levels of 26 plasma phospholipid FAs in metabolically healthy and unhealthy phenotypes in black South African adults. METHODS: Adults from the South African arm of the Prospective Urban and Rural Epidemiology study baseline (n = 711) were categorised into four groups, namely normal weight without metabolic syndrome (MetS) (MHNW), normal weight with MetS (MUNW), metabolically healthy overweight/obese (MHO) and metabolically unhealthy overweight/obese (MUO). Dietary and plasma phospholipid FAs were measured by a quantitative food frequency questionnaire and gas chromatography-tandem mass spectrometry, respectively. We compared dietary FAs, plasma phospholipid FAs, and estimated desaturase activity between the metabolic status groups using ANCOVA adjusted for age and energy intake. RESULTS: MetS was diagnosed in 35% of the participants. After adjustment for age and total energy intake, in comparison to the MHNW reference group, saturated dietary FAs (C14:0 to C18:0) and alpha-linolenic acid intakes were higher in both overweight/obese groups (MHO and MUO), while linoleic acid intakes were higher in the MUO group only. Plasma levels of most saturated FAs (C18:0 to C22:0) and PUFAs were higher, whereas selected MUFAs, palmitic acid, and estimated desaturase activities were lower in the overweight/obese groups. CONCLUSIONS: The overweight groups generally had higher fat intakes than normal-weight groups, but lower plasma levels of palmitic, palmitoleic, oleic, cis-vaccenic and estimated desaturase activities. Therefore, in this population, lower plasma levels of palmitic, palmitoleic, oleic, and cis-vaccenic acids and decreased estimated desaturase activities may be biomarkers of abnormal metabolic health in overweight/obese study participants.

Plasma phospholipid fatty acids are associated with altered fibrin clot properties in a population-based setting.

Evidence regarding the relationship of plasma clot properties with fatty acids is contradictory, owing to different experimental protocols employed. The relationship of fibrinogen and plasma fibrin clot properties with plasma phospholipid fatty acids were cross-sectionally investigated in a population-based setting in 900 individuals. Composite saturated fatty acids (driven by stearic acid) and composite n-3 and n-6 polyunsaturated fatty acids (driven by docosahexaenoic and arachidonic acid respectively) were associated with prothrombotic clot properties. Composite monounsaturated fatty acids (driven by oleic acid) were associated with a profibrinolytic clot phenotype. Fibrinogen and BMI partly mediated these relationships. Individual plasma fatty acids from the same composite group had opposing associations with clot properties indicating that associations with composite fatty acid groups is dependent on the relative composition of the comprising fatty acids. The relationship of the plasma phospholipid fatty acid profile with disease should not be interpreted without considering the role of regulatory mechanisms.

Waist circumference percentiles of black South African children aged 10 - 14 years from different study sites

Background. Waist circumference (WC) is a useful predictor of cardiometabolic risk in children. Published data on WC percentiles of children from African countries are limited.Objectives. To describe age- and sex-specific Wpercentiles in black South African (SA) children from different study sites, and compare these percentiles with median WCpercentiles of African-American (AA) children.Methods. Secondary data on WC for 10 - 14-year-old black SA children (N=4 954; 2 406 boys and 2 548 girls) were extracted from the data sets of six studies. Smoothed WC percentile curves for boys and girls were constructed using the LMS method. The 50th percentile for age- and sex-specific WC measurements was compared across study sites and with AA counterparts.Results. Girls had higher WC values than boys from the 50th to 95th percentiles at all ages. The 50th WC percentiles of all groups of SA children combined were lower than those of AA children. When SA groups were considered separately, Western Cape children had median WC values similar to AA children, while rural Limpopo children had the lowest WC values. The 95th percentiles for Western Cape girls exceeded the adult cutoff point for metabolic syndrome (WC ≥80 cm) from age 11years.Conclusions. The differences in WC values for 10 - 14-year-old children across the six study sites highlight the need for nationally representative data to develop age-, sex- and ethnic-specific WC percentiles for black SA children. The results raise concerns about high WC among Western Cape girls

South African dyslipidaemia guideline consensus statement: 2018 update A joint statement from the South African Heart Association (SA Heart) and the Lipid and Atherosclerosis Society of Southern Africa (LASSA).

South Africa (SA) is home to a heterogeneous population with a wide range of cardiovascular risk factors. Cholesterol reduction in combination with aggressive management of modifiable risk factors, including nutrition, physical activity, blood pressure and smoking, can help to reduce and prevent morbidity and mortality in individuals who are at increased risk of cardiovascular events. This updated consensus guide to management of dyslipidaemia in SA is based on the updated European Society of Cardiology and European Atherosclerosis Society dyslipidaemia guidelines published in 2016. For individuals who are not considered to be at high or very high cardiovascular risk, the decision whether to treat and which interventional strategy to use is based on a cardiovascular risk score calculated using total cholesterol, high-density lipoprotein cholesterol (HDL-C), gender, age and smoking status. The cardiovascular risk score refers to the 10-year risk of any cardiovascular event and includes 4 categories of risk (low, moderate, high and very high). People with established cardiovascular disease, diabetes mellitus, chronic kidney disease and genetic or severe dyslipidaemias are considered to already be at high or very high risk and do not require risk scoring. Therapeutic lifestyle change is the mainstay of management for all patients. The need for and intensity of drug therapy is determined according to baseline low-density lipoprotein (LDL-C) levels and the target LDL-C concentration appropriate to the individual. LDL-C treatment targets are based on pre-treatment risk and are as follows: <3 mmol/L in low- and moderate risk cases; <2.5 mmol/L and a reduction of at least 50% if the baseline concentration is 2.5 - 5.2 mmol/L in high-risk cases; and <1.8 mmol/L and a reduction of at least 50% if the baseline concentration is 1.8 - 3.5 mmol/L in very high-risk cases. A statin is usually recommended first-line; the specific agent is based on the required degree of cholesterol reduction, comorbidities and co-prescribed medication. Special attention should be paid to children with a family history of genetic or severe dyslipidaemia, who should be screened for dyslipidaemia from 8 years of age. In SA, HIV infection is not considered to be a significant cardiovascular risk factor and treatment recommendations for HIV-positive individuals are the same as for the general population, with careful choice of pharmacotherapy to avoid potential adverse drug-drug interactions. The benefit of statins in individuals older than 70 years is uncertain and clinical judgement should be used to guide treatment decisions and to avoid side-effects and overmedication in this group.

Low immune cell ARA and high plasma 12-HETE and 17-HDHA in iron-deficient South African school children with allergy.

Allergy has been associated with altered fatty acid and inflammatory status. In this cross-sectional study of 321 rural iron deficient (ID) South African children (aged 6-11 years), a subsample (n=111) of children with parent-reported allergy data were divided into an allergic (n=30) and non-allergic (n=81) group and compared. PBMC arachidonic acid (ARA; P=0.010) and the PBMC ARA to dihomo-gamma-linolenic acid (DGLA) ratio (P=0.035) were lower in the allergic children. Plasma 12-hydroxyeicosatetraenoic acid and 17-hydroxydocosahexaenoic acid (17-HDHA) were higher (P=0.040 and 0.020, respectively) in the allergic group. Thus, a fatty acid composition and lipid mediator levels indicative of increased release of ARA from PBMC membranes, increased inflammation as well as the resolving thereof, were associated with parent-reported allergy symptoms. This study used baseline data of an intervention study which was registered at clinicaltrials.gov as NCT01092377.

Iron and a mixture of DHA and EPA supplementation, alone and in combination, affect bioactive lipid signalling and morbidity of iron deficient South African school children in a two-by-two randomised controlled trial.

We recently reported that iron supplementation increased respiratory morbidity in iron deficient South African children. This increase, however, was attenuated when iron was provided in combination with a mixture of DHA/EPA. To explore potential underlying mechanisms, we examined the effects of iron and DHA/EPA, alone and in combination, on plasma lipid-derived immune modulator concentrations and related gene expression in peripheral blood mononuclear cells (PBMC). DHA/EPA decreased inflammatory 12-hydroxyeicosatetraenoic acid and tended to increase anti-inflammatory and pro-resolving 17-hydroxydocosahexaenoic acid (17-HDHA), while iron decreased 17-HDHA. However, in combination with iron, the anti-inflammatory effect of DHA/EPA was maintained. These biochemical changes may explain the prevention of iron-induced respiratory morbidity that we observed when iron was supplemented in combination with DHA/EPA during the 8.5 month randomised controlled trial and might lead to a safer approach of delivering iron supplementation. The study was registered at clinicaltrials.gov as NCT01092377.

Overweight impairs efficacy of iron supplementation in iron-deficient South African children: a randomized controlled intervention.

BACKGROUND: Many countries in the nutrition transition have high rates of iron deficiency (ID) and overweight (OW). ID is more common in OW children; this may be due to adiposity-related inflammation reducing iron absorption. OBJECTIVE: We investigated whether weight status predicts response to oral iron supplementation in ID South African children. DESIGN: A placebo-controlled trial of oral iron supplementation (50 mg, 4 × weeks for 8.5 months) was done in ID 6- to 11-year-old children (n=321); 28% were OW or obese. BMI-for-age z-scores (BAZ), hepcidin (in a sub-sample), hemoglobin, serum ferritin (SF), transferrin receptor (TfR), zinc protoporphyrin (ZnPP) and C-reactive protein (CRP) were measured; body iron was calculated from the SF to TfR ratio. RESULTS: At baseline, BAZ correlated with CRP (r=0.201, P<0.001) and CRP correlated with hepcidin (r=0.384, P<0.001). Normal weight children supplemented with iron had significantly lower TfR concentrations at endpoint than the OW children supplemented with iron and the children receiving placebo. Higher BAZ predicted higher TfR (ß=0.232, P<0.001) and lower body iron (ß=-0.090, P=0.016) at endpoint, and increased the odds ratio (OR) for remaining ID at endpoint in both the iron and placebo groups (iron: OR 2.31, 95% CI: 1.13, 4.73; placebo: OR 1.78, 95% CI: 1.09, 2.91). In the children supplemented with iron, baseline hepcidin and BAZ were significant predictors of endpoint TfR, with a trend towards a hepcidin × BAZ interaction (P=0.058). CONCLUSION: South African children with high BAZ have a two-fold higher risk of remaining ID after iron supplementation. This may be due to their higher hepcidin concentrations reducing iron absorption. Thus, the current surge in OW in rapidly developing countries may undercut efforts to control anemia in vulnerable groups. The trial is registered at clinicaltrials.gov as NCT01092377.

Primary Health Care Facility Infrastructure and Services and The Nutritional Status of Children 0 to 71 Months Old and Their Caregivers Attending These Facilities in Four Rural Districts in The Eastern Cape and Kwazulu-Natal Provinces; South Africa

Objective: To assess primary health care (PHC) facility infrastructure and services; and the nutritional status of 0 to 71-month-old children and their caregivers attending PHC facilities in the Eastern Cape (EC) and KwaZulu-Natal (KZN) provinces in South Africa. Design: Cross-sectional survey. Setting: Rural districts in the EC (OR Tambo and Alfred Nzo) and KZN (Umkhanyakude and Zululand). Subjects: PHC facilities and nurses (EC: n = 20; KZN: n = 20); and 0 to 71-month-old children and their caregivers (EC: n = 994; KZN: n = 992). Methods: Structured interviewer-administered questionnaires and anthropometric survey. Results: Of the 40 PHC facilities; 14 had been built or renovated after 1994. The PHC facilities had access to the following: safe drinking water (EC: 20; KZN: 25); electricity (EC: 45; KZN: 85); flush toilets (EC: 40; KZN: 75); and operational telephones (EC: 20; KZN: 5). According to more than 80of the nurses; problems with basic resources and existing cultural practices influenced the quality of services. Home births were common (EC: 41; KZN: 25). Social grants were reported as a main source of income (EC: 33; KZN: 28). Few households reported that they had enough food at all times (EC: 15; KZN: 7). The reported prevalence of diarrhoea was high (EC: 34; KZN: 38). Undernutrition in 0 to younger than 6 month-olds was low; thereafter; however; stunting in children aged 6 to 59 months (EC: 22; KZN: 24) and 60 to 71 months (EC: 26; KZN: 31) was medium to high. Overweight and obese adults (EC: 49; KZN: 42) coexisted. Conclusion: Problems regarding infrastructure; basic resources and services adversely affected PHC service delivery and the well-being of rural people; and therefore need urgent attention

Risk Factors of Poor Anthropometric Status in Children Under Five Years of Age Living In Rural Districts of the Eastern Cape and Kwazulu-Natal Provinces; South Africa

Objectives: Factors associated with children's anthropometric status were determined. Design: Secondary analysis was done using data from a cross-sectional survey including children under five years of age (n = 2 485) and their mothers in rural districts of the Eastern Cape and KwaZulu-Natal provinces; South Africa. Methods: Data generated by questionnaire and anthropometric indices were used to construct a logistic regression model; taking into account hierarchical relationships of risk factors to determine the odds of a child being stunted; underweight or overweight. Statistical significance was set at p 0.05. Results: Factors associated with stunting were child of male gender (odds ratio (OR)

Risk Factors of Poor Anthropometric Status in Children Under Five Years of Age Living In Rural Districts of the Eastern Cape and Kwazulu-Natal Provinces; South Africa

Objectives: Factors associated with children's anthropometric status were determined. Design: Secondary analysis was done using data from a cross-sectional survey including children under five years of age (n = 2 485) and their mothers in rural districts of the Eastern Cape and KwaZulu-Natal provinces; South Africa. Methods: Data generated by questionnaire and anthropometric indices were used to construct a logistic regression model; taking into account hierarchical relationships of risk factors to determine the odds of a child being stunted; underweight or overweight. Statistical significance was set at p 0.05. Results: Factors associated with stunting were child of male gender (odds ratio (OR)

Erythrocyte membrane fatty acids in patients with multiple sclerosis.

BACKGROUND: Reports on fatty acids levels in multiple sclerosis remain inconclusive. OBJECTIVE: To determine the erythrocyte membrane fatty acid levels in multiple sclerosis patients and correlate with Kurtzke Expanded Disability Status Scale. METHODS: Fatty acid composition of 31 multiple sclerosis and 30 control individuals were measured by gas chromatography. RESULTS: The membrane phosphatidylcholine C20:4n - 6 concentration was lower in the multiple sclerosis patients when compared to that of the control group, P = 0.04 and it correlated inversely with the EDSS and FSS. CONCLUSION: Decrease in C20:4n - 6 in the erythrocyte membrane could be an indication of depleted plasma stores, and a reflection of disease severity.

Substitution of high monounsaturated fatty acid avocado for mixed dietary fats during an energy-restricted diet: effects on weight loss, serum lipids, fibrinogen, and vascular function.

OBJECTIVE: First, we wanted to dispel the myth that avocados are fattening and therefore should be avoided in energy-restricted diets. Second, we examined the effects of avocados, a rich source of monounsaturated fatty acids, as part of an energy-restricted diet on weight loss, serum lipids, fibrinogen, and vascular function in overweight and obese subjects. METHODS: Sixty-one free-living volunteers (13 men and 48 women), with body mass index of 32 +/- 3.9 kg/m(2) (mean +/- standard deviation) participated in this randomized, controlled, parallel study. Subjects were paired and randomly assigned to one of two groups. The experimental group consumed 200 g/d of avocado (30.6 g of fat), which substituted for 30 g of other mixed dietary fats such as margarine or oil, and the control group excluded avocado from their energy-restricted diet for 6 wk. Seven-day isoenergetic menus were planned according to mean energy requirements of both sexes to provide total energy intakes consisting of 30% fat, 55% carbohydrates, and 15% protein. Anthropometric measurements, physical activity, blood pressure, and arterial compliance were measured with standard methods at the beginning and end of the intervention. Fasting blood samples were drawn at the beginning and end of the intervention. RESULTS: Fifty-five subjects completed the study. The compliance rate to avocado intake in the experimental group was 94.6%. The percentage of plasma oleic acid increased significantly with the consumption of avocado in the experimental group, whereas a decrease was seen in the percentage of myristic acid from baseline to the end of the intervention in both groups but was significant only in the experimental group. Anthropometric measurements (body mass, body mass index, and percentage of body fat) decreased significantly in both groups during the study (P < 0.001), and the change was similar in both groups. Serum lipid concentrations (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triacylglycerols), fibrinogen, blood pressure, and arterial compliance did not change significantly within or between groups. CONCLUSION: The consumption of 200 g/d of avocado within an energy-restricted diet does not compromise weight loss when substituted for 30 g of mixed dietary fat. Serum lipid concentrations, plasma fibrinogen, arterial compliance, and systolic and diastolic blood pressures were not affected by weight loss or avocado intake.

Dietary modulation of fatty acid profiles and oxidative status of rat hepatocyte nodules: effect of different n-6/n-3 fatty acid ratios.

Male Fischer rats were fed the AIN 76A diet containing varying n-6/n-3 FA ratios using sunflower oil (SFO), soybean oil (SOY), and SFO supplemented with EPA-50 and GLA-80 (GLA) as fat sources. Hepatocyte nodules, induced using diethylnitrosamine followed by 2-acetylaminofluorene/partial hepatectomy promotion, were harvested, with surrounding and respective dietary control tissues, 3 mon after partial hepatectomy. The altered growth pattern of hepatocyte nodules in rats fed SFO is associated with a distinct lipid pattern entailing an increased concentration of PE, resulting in increased levels of 20:4n-6. In addition, there is an accumulation of 18:1 n-9 and 18:2n-6 and a decrease in the end products of the n-3 metabolic pathway in PC, suggesting a dysfunctional delta-6-desaturase enzyme. The hepatocyte nodules of the SFO-fed rats exhibited a significantly reduced lipid peroxidation level that was associated with an increase in the glutathione (GSH) concentration. The low n-6/n-3 FA ratio diets significantly decreased 20:4n-6 in PC and PE phospholipid fractions with a concomitant increase in 20:5n-3, 22:5n-3, and 22:6n-3. The resultant changes in the 20:4/20:5 FA ratio and the 20:3n-6 FA level in the case of the GLA diet suggest a reduction of prostaglandin synthesis of the 2-series. The GLA diet also counteracted the increased level of 20:4n-6 in PE by equalizing the nodule/surrounding ratio. The low n-6/n-3 ratio diets significantly increased lipid peroxidation levels in hepatocyte nodules, mimicking the level in the surrounding and control tissue while GSH was decreased. An increase in n-3 FA levels and oxidative status resulted in a reduction in the number of glutathione-S-transferase positive foci in the liver of the GLA-fed rats. Modulation of cancer development with low n-6/n-3 ratio diets containing specific dietary FA could be a promising tool in cancer intervention in the liver.

Lipids and delta6-desaturase activity alterations in rat liver microsomal membranes induced by fumonisin B1.

Alterations in the membrane structure and function of hepatocyte membranes by fumonisin B1 (FB1) have been proposed to play an important role in the disruption of growth regulatory effects and hence in the cancer-promoting ability of the mycotoxin. Detailed analyses of lipids in liver microsomal fractions of rats exposed to different dietary levels of FB1 over a period of 21 d indicated an increase in PC, PE, PI, and cholesterol (Chol). These changes decreased the PC/PE and increased the total phospholipid/Chol ratios. When considering FA content, the quantities of total FA increased (P < 0.05) in the major phospholipid fractions as a result of the increased phospholipid levels. However, when considering the relative levels (mg/100 mg of the total FA) of specific FA, the monounsaturated FA (16:1 n-7 and 18:1n-9) and 18:2n-6 increased (P < 0.05), whereas the long-chain PUFA decreased (P < 0.05) in the main phospholipid fractions. Enzyme analyses indicated that the activity of the delta6-desaturase was significantly reduced in liver microsomal preparations in a dose-dependent manner. An increase in the 20:3n-6/20:4n-6 ratio also suggested a decrease in the activity of the delta5-desaturase. Disruption of microsomal lipid metabolism at different levels by FB1 could play an important role in the alteration of growth regulatory effects in the liver.

Fumonisin-induced hepatocarcinogenesis: mechanisms related to cancer initiation and promotion.

We review the hepatocarcinogenic effects of fungal cultures of Fusarium verticillioides(= Fusarium moniliforme) strain MRC 826 in male BD IX rats. Subsequent chemical analyses of the fumonisin B (FB) mycotoxin content in the culture material used and long-term carcinogenesis studies with purified FB1 provide information about dose-response effects, relevance of hepatotoxicity during FB1-induced carcinogenesis, and the existence of a no-effect threshold. Fumonisin intake levels of between 0.08 and 0.16 mg FB/100 g body weight (bw)/day over approximately 2 years produce liver cancer in male BD IX rats. Exposure levels < 0.08 mg FB/100 g bw/day fail to induce cancer, although mild toxic and preneoplastic lesions are induced. The nutritional status of the diets used in the long-term experiments was marginally deficient in lipotropes and vitamins and could have played an important modulating role in fumonisin-induced hepatocarcinogenesis. Short-term studies in a cancer initiation/promotion model in rat liver provided important information about the possible mechanisms involved during the initial stages of cancer development by this apparently nongenotoxic mycotoxin. These studies supported the findings of long-term investigations indicating that a cytotoxic/proliferative response is required for cancer induction and that a no-effect threshold exists for cancer induction. The mechanisms proposed for cancer induction are highlighted and include the possible role of oxidative damage during initiation and the disruption of lipid metabolism, integrity of cellular membranes, and altered growth-regulatory responses as important events during promotion.

Changes in essential fatty acid patterns associated with normal liver regeneration and the progression of hepatocyte nodules in rat hepatocarcinogenesis.

Changes in lipid metabolism were monitored in rat hepatocyte nodules at certain time points over 9 months. Tissue obtained from partially hepatectomized rats, collected over a period of 7 days, were included as a control for normal hepatocyte cell proliferation. Two important features regarding the lipid profiles of hepatocyte nodules and normal regenerating liver were the increased concentrations of phosphatidylethanolamine (PE), resulting in a decreased phosphatidylcholine/phosphatidylethanolamine (PC/PE) ratio, and cholesterol. These changes coincided with increased membrane fluidity in the nodules and regenerating liver. With respect to the fatty acid (FA) profiles of the nodules, C18:1omega9 and C18:2omega6 increased in PE and PC whereas C20:4omega6 decreased in PC and increased in PE. C22:5omega6 and C22:6omega3, the end products of the omega6 and omega3 metabolic pathways, respectively, decreased in PC and remained unchanged in PE. The FA levels in PC reflected an impaired delta-6 desaturase enzyme, whereas this effect was masked in PE due to the increased concentration of this phospholipid fraction. In regenerating liver, the FA profiles of PC and PE showed the same pattern as described for the hepatocyte nodules, except for C18:1omega9 which decreased in PC and increased non-significantly in PE. The increased C18:1omega9 level, a FA with anti-oxidative properties, as well as the decreased levels of the long-chain polyunsaturated fatty acids (C20 and C22 carbon chains), have been associated with the decreased lipid peroxidation level in hepatocyte nodules. The resultant decrease in peroxidative metabolites, known to affect apoptosis, could be important in the progression of the nodules into neoplasia. The present results indicate that the altered lipid parameters associated with hepatocyte nodules closely mimics cellular proliferation in regenerating liver and could be responsible for the enhanced proliferation and/or altered growth pattern in these lesions. The altered FA profiles suggest various pathways in which FA could play a role in transmembrane signalling related to the altered cell proliferative and apoptotic pathways. The persistent changes in the hepatocyte nodules suggest that the lipid metabolism escapes the regulatory mechanisms required for normal cellular homeostasis at different levels.

Long-term evaluation of a micronutrient-fortified biscuit used for addressing micronutrient deficiencies in primary school children.

OBJECTIVE: To evaluate the long-term effect on micronutrient status of a beta-carotene-, iron- and iodine-fortified biscuit given to primary school children as school feeding. DESIGN: Children receiving the fortified biscuit were followed in a longitudinal study for 2.5 years (n = 108); in addition, cross-sectional data from three subsequent surveys conducted in the same school are reported. SETTING: A rural community in KwaZulu-Natal, South Africa. SUBJECTS: Children aged 6-11 years attending the primary school where the biscuit was distributed. RESULTS: There was a significant improvement in serum retinol, serum ferritin, haemoglobin, transferrin saturation and urinary iodine during the first 12 months of the biscuit intervention. However, when the school reopened after the summer holidays, all variables, except urinary iodine, returned to pre-intervention levels. Serum retinol increased again during the next 9 months, but was significantly lower in a subsequent cross-sectional survey carried out directly after the summer holidays; this pattern was repeated in two further cross-sectional surveys. Haemoglobin gradually deteriorated at each subsequent assessment, as did serum ferritin (apart from a slight increase at the 42-month assessment at the end of the school year). CONCLUSIONS: This study has shown that fortification of a biscuit with beta-carotene at a level of 50% of the Recommended Dietary Allowance (RDA) was enough to maintain serum retinol concentrations from day to day, but not enough to sustain levels during the long school holiday break. Other long-term solutions, such as local food production programmes combined with nutrition education, should also be examined. The choice of the iron compound used as fortificant in the biscuit needs further investigation.

The effect of evening primrose oil on the radiation response and blood flow of mouse normal and tumour tissue.

PURPOSE: To investigate the effect of the oral administration of evening primrose oil on the radiation response and the blood flow of normal tissue and a tumour in BALB/c mice. METHODS AND MATERIALS: Aliquots of evening primrose oil were fed to BALB/c mice daily and the radiation response of the skin was assessed by the determination of ED50 values for the incidence of moist desquamation, using probit analysis. Tumour radiosensitivity was investigated by determining the growth delay caused by irradiation of a transplantable rhabdomyosarcoma. The 86RbCl uptake technique was used to determine the blood flow in normal foot and tumour tissue. The fatty-acid content of red blood cells, plasma and tumour tissue was measured using gas chromatography. RESULTS: Daily evening primrose oil dietary supplementation reduced the sensitivity of skin to radiation-induced moist desquamation and prevented the radiation-associated increase in blood flow that was observed in this tissue. No modification of tumour blood flow or of tumour sensitivity to radiation resulted from evening primrose oil supplementation of mice. Evening primrose oil supplementation resulted in changes in plasma levels of linoleic acid (LA), gamma-linolenic acid (GLA), dihomo-gamma-linolenic acid (DGLA) and arachidonic acid (AA). These changes were contingent on whether the mice had been irradiated or not. In red blood cells evening primrose oil supplementation increased the GLA level of unirradiated mice and the LA level at 20 days after irradiation. There were no changes in tumour fatty-acid levels as a result of evening primrose oil treatment. CONCLUSIONS: Daily evening primrose oil supplementation reduced the sensitivity of skin to radiation-induced moist desquamation but did not alter tumour sensitivity to radiation.

Effect of palm oil on plasma lipoprotein concentrations and plasma low-density lipoprotein composition in non-human primates.

Palm oil (PO) contains approximately 43% of palmitic acid. It is the most abundant saturated fatty acid in the diet and it is generally considered the primary cholesterol (C)-raising fatty acid. However, the effect of palmitic acid on plasma cholesterol appears to depend on the cholesterol content of the diet. The aim of this study was to determine the effect of PO with either a high-fat, high-C or moderate-fat, moderate-C diet on lipoprotein C and low-density lipoprotein (LDL) composition. Fifty adult, male vervet monkeys were randomly assigned to the high-fat diet group (HFD: 35%E fat, approximately 0.106 mg C/kJ; n = 30) and the moderate-fat diet group (MFD: 30%E fat, approximately 0.027 mg C/kJ; n = 30). Baseline LDL-C, high-density lipoprotein (HDL)-C and body weight were used to stratify the vervets into comparable experimental groups within each dietary group. The HFD group was divided into two groups of 10 each: one group continued with the HFD in which 8.1%E was derived from lard (AF); in the other group, AF was substituted isocalorically with PO. The MFD group was divided into three groups of 10 each: one group continued with the MFD in which 11.8%E was derived from AF; in the other two groups, the AF was substituted isocalorically with either sunflower oil (SO) or PO. This article presents preliminary results on plasma lipoproteins and LDL composition after 6 months of dietary intervention. Plasma total and LDL-C was higher in all the groups, but the mean changes elicited by PO with either the HFD or MFD were no different from that observed with AF and SO. There was no difference in the mean change of LDL molecular weight within the HFD and MFD. It is concluded that PO is no different from AF (HFD and MFD) or SO (MFD) in its cholesterolaemic effect.