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Background High density lipoprotein cholesterol (HDL-C) concentration correlates inversely with atherosclerotic cardiovascular disease (ASCVD) risk and is included in risk calculations. Endothelial lipase (EL) is a phospholipase that remodels HDL. Deficiency of EL due to mutations in its gene, LIPG, is associated with hyperalphalipoproteinemia. The effects of EL on HDL function and ASCVD risk remain poorly understood. Objectives To determine whether hyperalphalipoproteinemia due to EL deficiency is protective against ASCVD. Methods We identified LIPG variants amongst patients with severe hyperalphalipoproteinemia (HDL-C >2.5 mmol/L) attending a referral lipid clinic in the Western Cape Province of South Africa. We analysed the clinical and biochemical phenotypes amongst primary hyperalphalipoproteinemia cases (males HDL-C >1.6 mmol/L; females HDL-C >1.8 mmol/L) due to LIPG variants, and the distribution of variants in normal and hyperalphalipoproteinemia ranges of HDL-C. Results 1007 patients with HDL-C concentration ranging from 1.2 to 4.5 mmol/L were included. Seventeen females had primary hyperalphalipoproteinemia. Vascular disease was prominent, but not associated with HDL-C concentration, LDL-C concentration or carotid artery intima media thickness. Two novel and three known LIPG variants were identified in severe hyperalphalipoproteinemia. Four additional variants were identified in the extended cohort. Two common variants appeared normally distributed across the HDL-C concentration range, while six less-common variants were found only at higher HDL-C concentrations. One rare variant had a moderate effect. Conclusion Hyperalphalipoproteinemia due to LIPG variants is commoner in females and may not protect against ASCVD. Use of current risk calculations may be inappropriate in patients with hyperalphalipoproteinemia due to EL deficiency. Our study cautions targeting EL to reduce risk.

Many attempts have been made to define and reconstruct the most plausible ecological and dietary niche of the earliest members of the human species. While earlier models emphasise big-game hunting in terrestrial, largely savannah environments, more recent scenarios consider the role of marine and aquatic foods as a source of polyunsaturated fatty acids (PUFA) and other brain-selective nutrients. Along the coast of southern Africa, there appears to be an association between the emergence of anatomically modern humans and accumulation of some of the earliest shell middens during the Middle Stone Age (200–40 ka). Fragmentary fossil remains classified as those of anatomically modern humans, along with marine food residues and numerous material cultural indicators of increased social and behavioural complexity have been recovered from coastal sites. In this paper, new information on the nutrient content of marine and terrestrial foods available to early modern humans in the southwestern Cape is presented and compared with existing data on the nutritional value of some wild plant and animal foods in Africa. The results suggest that coastal foraging, particularly the collection of abundant and predictable marine molluscs, would have allowed early modern humans to exploit some of the richest and most accessible sources of protein, micronutrients and longer-chain omega-6 and omega-3 fatty acids. Reliable and accessible sources of omega-3 eicosapentaenoic and docosahexaenoic acid are considerably more restricted in terrestrial foods.

Background. Criteria for labelling infant feeds as suitable for the dietary management of cow’s milk protein allergy (CMPA) rely on proving the hypoallergenicity of such feeds or clinical studies showing that the feeds are tolerated by 90% of children with proven CMPA. South African (SA) labelling legislation does not indicate what testing is necessary to prove hypoallergenicity. Objectives. To evaluate all extensively hydrolysed cow’s milk formulas and amino acid-based formulas available in SA for residual allergen content, protein size and amino-acid content. Results. All amino-acid and extensively hydrolysed formulas were found to be similar in composition, with no residual cow’s milk allergens detectable by enzyme-linked immunosorbent assay. Furthermore, proteins were absent and only small molecules in the size range of amino acids and possibly of very small oligopeptides were detected. Conclusions. These findings indicate that the formulas are extremely likely to be compliant with the definition of hypoallergenicity as tolerance in 90% of proven sufferers from cow’s milk allergy. The formulas may therefore be labelled as suitable for the dietary management of infants with CMPA.

Paraoxonase 1 (PON1) activity is markedly influenced by coding polymorphisms, Q/R at position 192 and M/L at position 55 of the PON1 gene. We investigated the frequencies of these polymorphisms and their effects on PON1 and antioxidant activities in 844 South African mixed ancestry individuals. Genotyping was done using allele-specific TaqMan technology, PON1 activities were measured using paraoxon and phenylacetate, oxidative status was determined by measuring the antioxidant activities of ferric reducing antioxidant power and trolox equivalent antioxidant capacity, and lipid peroxidation markers included malondialdehyde and oxidized LDL. The frequencies of Q192R and L55M were 47.6% and 28.8%, respectively, and the most common corresponding alleles were 192R (60.4%) and 55M (82.6%). TheQ192was significantly associated with 5.8 units’ increase in PON1 concentration and 15.4 units’ decrease in PONase activity after adjustment for age, sex, BMI, and diabetes, with suggestion of differential effects by diabetes status. The PON1L55variant was associated with none of the measured indices. In conclusion, we have shown that the Q192R polymorphism is a determinant of both PON1 concentration and activity and this association appeared to be enhanced in subjects with diabetes.

Epidemiological evidence suggests cardiovascular benefits from the consumption of alcoholic beverages, but corroboration by functional and outcome studies is still outstanding. Non-invasive functional tests on the brachial arteries of healthy volunteers were performed before and for two hours after consuming red wine. Brachial artery dimensions were determined by ultrasound at baseline, 30, 60 and 120 min. Flow-mediated dilatation (FMD) was similarly assessed. Putative minimum and maximum lumen diameters were determined after ice immersion and sublingual trinitroglycerine (TNG) at baseline and 60 min after wine consumption. Sixteen subjects had a mean resting brachial artery diameter of 3.84 mm, which significantly increased with wine to 4.44 mm at 30 min, 4.39 mm at 60 min and 4.49 mm at 120 min. The calculated blood flow rates during the study did not differ significantly over the measured intervals. The baseline mean diameter with TNG was not significantly different from the dilation with wine. The vasoconstrictor response varied, with a -2.6 ± 2.9% change with wine, compared with the baseline diameter. There was appreciable variation of the diameter relative to the range found with ice and TNG. The calculated FMDs (% changes) for the study were 10.8, 6.1, 5.6 and 7.5, indicating statistically significant effects of wine (p < 0.0001). The authors conclude that red wine consumption leads to beneficial arterial effects that may relate to different doses or other mechanisms than FMD. Further studies need to be done to discriminate between the effects of alcohol and phenolic compounds on vascular function.

The metabolic syndrome is a target for the dietary prevention of cardiovascular disease. The effect of adding red wine to the diet has not been fully investigated. This study examined whether a Mediterranean-type diet complemented with red wine and mild exercise had an impact on patients with the metabolic syndrome in the short term. Twelve patients with the metabolic syndrome consumed a Mediterranean-type diet for four weeks without and with red wine respectively and performed mild exercise. We implemented the diagnostic criteria for the metabolic syndrome as formulated by the Adult Treatment Panel III (ATP III) in 2001. The patients were also screened for multiple genetic markers implicated in cardiovascular disease. Weight, body mass index, abdominal circumference and blood pressure were measured, as well as various biochemical, haematological and inflammatory markers. There was a significant decrease in the body weight (p = 0.04) and an increase in ORAC value (p = 0.035) after the dietary intervention. A significant decrease in systolic blood pressure (p = 0.045) was observed. Red wine had no additional benefits. Although diet reduced weight and blood pressure, the lipoprotein and pro-coagulant profiles of patients with the metabolic syndrome were not affected in this study. These findings may be explained partly by the diverse genetic profile identified among the study participants, as 50% had mutations involved in lipid metabolism that may influence the response to dietary intervention and alcohol consumption.

Letter by Nutten et al. on article by Levin et al . (Levin ME, Blackhurst DM, Kirstein F, Kok D, van der Watt GF, Marais AD. Residual allergenicity of amino acid-based and extensively hydrolysed cow’s milk formulas. S Afr Med J 2017;107(9):763-767. S Afr Med J 2017;107(3):258-263. https://doi.org/10.7196/SAMJ.2017.v107i9.12137); and response by Levin et al .

The wide acceptance of the oxidation theory of atherogenesis has prompted attention to antioxidant mechanisms, particularly the prevention of lipid oxidation by high-density lipoprotein-associated proteins like paraoxonase 1 (PON1) enzyme. PON1 is a calcium-dependent enzyme that has interested toxicologists since its discovery as an organophosphate hydrolase. There is a growing interest in the enzyme's importance in cardiovascular health prompted by evidence that it may have a role in lipid metabolism and the development of atherosclerosis via its antioxidant effects. PON1 is capable of hydrolyzing homocysteine thiolactone, a metabolite of homocysteine that can impair protein function leading to endothelial dysfunction and vascular damage. Although this lactonase activity has been suggested to be PON1's native activity, the enzyme's specific physiological role and substrate remain unclear. In this review, we summarize developments in the field of PON1 research relating to cardiovascular health, and highlight those that perhaps warrant further research.

A total of 43 individuals were included in a study of genetic and environmental factors associated with cardiovascular disease; seven subjects (16%) were diagnosed with the metabolic syndrome. A statistically significant association was observed between the E2 allele of the apolipoprotein E (Apo E) polymorphism and an increasing number of metabolic syndrome features (p = 0.03). Clinical and biochemical abnormalities identified could be ascribed to the combined effects of unfavorable genotypes and environmental factors known to interact with the Apo E gene. Excessive alcohol intake, high-calorie diets and smoking should be restricted in individuals with the Apo E2 and/or E4 alleles, which are associated with a significantly increased risk of cardiovascular disease.

We evaluated the association of indices of paraoxonase (PON1) and oxidative status with subclinical cardiovascular disease (CVD) in mixed-ancestry South Africans. Participants were 491 adults (126 men) who were stratified by diabetes status and body mass index (BMI). Carotid intima-media thickness (CIMT) was used as a measure of subclinical CVD. Indices of PON1 and oxidative status were determined by measuring levels and activities (paraoxonase and arylesterase) of PON1, antioxidant activity (ferric reducing antioxidant power and trolox equivalent antioxidant capacity), and lipid peroxidation markers (malondialdehyde and oxidized LDL). Diabetic subjects (28.9%) displayed a significant decrease in PON1 status and antioxidant activity as well as increase in oxidized LDL and malondialdehyde. A similar profile was apparent across increasing BMI categories. CIMT was higher in diabetic than nondiabetic subjects(P<0.0001) but showed no variation across BMI categories. Overall, CIMT correlated negatively with indices of antioxidant activity and positively with measures of lipid oxidation. Sex, age, BMI, and diabetes altogether explained 29.2% of CIMT, with no further improvement from adding PON1 and/or antioxidant status indices. Though indices of PON1 and oxidative status correlate with CIMT, their measurements may not be useful for identifying subjects at high CVD risk in this population.

4but the collective term now includes arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), iron (Fe), lead (Pb), manganese (Mn), mercury (Hg), molybdenum (Mo), nickel (Ni), vanadium (V) and zinc (Zn). Some interest also exists in aluminium, cobalt, strontium and other rarer metals. Potassium, calcium and magnesium are expected in wine because of their high intracellular content. Physiologic roles are known for Fe (haem moeities of haemoglobin and cytochromes), Cu (amine oxidases, caeruloplasmin, dopamine hydrolase and collagen synthesis), Mn (superoxide dismutase), Zn (protein synthesis, stabilisation of DNA and RNA) with low requirements of Cr (glucose homeostasis). Other heavy metals ions are not believed to be essential to health, even in trace amounts.

Paraoxonase 1 (PON1) is increasingly measured on samples that have been stored for extended durations. The impact of storage and baseline conditions on the stability of the enzyme is however not well documented. We investigated the influence of hyperglycaemia on the stability of PON1 activity and antioxidant status in human sera stored for 12 months.Blood was collected from 60 individuals aged 35-80 years with chronic hyperglycaemia (HbA1c≥6.5%) or normoglycaemia (HbA1c6.5%) in Cape Town. At baseline and after 12 months at -80°C, levels of PON1 activity (paraoxoase and arylesterase), antioxidant activity (ferric reducing antioxidant power (FRAP) and Trolox equivalent antioxidant capacity (TEAC)) and lipid peroxidation (malondialdehyde and oxidised low density lipoprotein (ox-LDL)) were measured and compared.In normoglycaemic samples, 12-month storage led to minor alterations of10% for the six target variables. In hyperglycaemic samples, alterations ranged from 13% for AREase activity to about 23% for ox-LDLs indicating a twofold to fourfold difference between the two groups in the variables assessed. Changes in levels of FRAP, TEAC and ox-LDL were both statistically and clinically significant. Furthermore, there was evidence of significant statistical interaction by baseline glycaemic status on the alteration of FRAP, TEAC, thiobarbituric acid reactive substances and ox-LDL, but not for PON1 activity.The results indicate that baseline glycaemic status may contribute to a decline in the stability of antioxidant activity and extent of lipid peroxidation but not PON activity.

3-Ribosylurate is a dominant feature on high performance liquid chromatography (HPLC) profiles of acid extracts of erythrocytes from cows and buffalo, but is HPLC-undetectable in acid extracts of erythrocytes from all other species examined to date. Various aspects of this unique low molecular weight substance remain unexplored since it was first identified. In this study, the mutation(s) responsible for the appearance of ribosylurate in these cells is shown to be specific to members of both tribes of the Bovinae subfamily ( Bovidae family), being detectable in the erythrocytes of both the cow and the buffalo ( Bovini tribe) as well as in the kudu ( Strepsicerotini tribe), but not in representative species from the other subfamilies of the Bovidae family. More specifically, expression of the mutation(s) seems to be restricted to the erythrocyte lineage of these species, ribosylurate being undetectable in cow white blood cells and primary cultures of fibroblasts. Novel evidence is presented that ribosylurate has antioxidant activity. Accumulation of high levels specifically within the haemoglobin-rich milieu of circulating erythrocytes may serve to protect perfused tissues by removing pathophysiological levels of hydrogen peroxide from plasma. Maintenance of ribosylurate levels may be important in conditions associated with oxidative stress in Bovinae .

In South Africa, the plant Aspalathus linearis (Brum.f) Dahlg. (Fabaceae) is traditionally used as a "tea" referred to as rooibos or redbush. This plant has been listed as a medicinal plant based mostly on anecdotal evidence.Despite a long history of traditional use in South Africa, very little scientific data are available from controlled clinical trials confirming its popular use. The aim of the present study was to investigate the effect of rooibos on biochemical and oxidative stress parameters in adults at risk for cardiovascular disease.After a washout period of 2 weeks, 40 volunteers consumed six cups of fermented/traditional rooibos daily for 6 weeks, followed by a control period. Blood biochemical parameters indicative of antioxidant activity and content (total polyphenols), lipid peroxidation (conjugated dienes - CDs, thiobarbituric acid reactive substances - TBARS), redox status (total glutathione - tGSH, ratio of reduced to oxidized glutathione - GSH:GSSG), lipid profile (total cholesterol, low density lipoprotein - LDL and high density lipoprotein - HDL cholesterol and triacylglycerol levels) and liver and kidney function were measured at the end of each study period.Plasma antioxidant capacity was not altered, but plasma total polyphenol levels increased significantly after rooibos consumption compared with the control levels (from 79.8±16.9 mg/L to 89.8±14.1 mg/L). Significant decreases in plasma markers of lipid peroxidation were found after rooibos consumption, as reported by levels of CDs (167.3±29.5 nmol/mL vs. 108.8±20.1 nmol/mL) and TBARS (1.9±0.6 μmol/L vs. 0.9±0.3 μmol/L). Reduced glutathione (797±238 μmol/L vs. 1082±140 μmol/L) and the GSH:GSSG ratio (41±14 vs. 76±17) were both significantly increased after consumption of rooibos. The lipid profiles showed that rooibos consumption, compared with the control values, significantly decreased serum LDL-cholesterol (4.6±1.3 mmol/L vs. 3.9±0.7 mmol/L) and triacylglycerols (1.7±0.8 mmol/L vs. 1.2±0.7 mmol/L), while HDL-cholesterol (0.9±0.1 mmol/L vs. 1.2±0.2 mmol/L) was significantly increased.Confirming its popular use, consumption of fermented, traditional rooibos significantly improved the lipid profile as well as redox status, both relevant to heart disease, in adults at risk for developing cardiovascular disease.

Background and aims Atherosclerosis may be ameliorated by red wine consumption possibly by providing antioxidants. The effects of red wine on the peroxidation status of chylomicrons (CM) are unknown. The aims were to compare the lipid peroxidation status of oil rich in polyunsaturated fatty acids (PUFA) from a standardised high-fat meal with that of the CM at peak concentrations following ingestion of the meal with and without wine, and to examine the contribution of wine to the antioxidant content of the plasma. Methods and results Fasted subjects ingested the meal randomly with and without red wine. The peroxidation status was described by conjugated dienes (CD), lipid hydroperoxides (LOOH) and thiobarbituric acid reactive substances (TBARS). CM lag times and the area under the curve (AUC) of CD were determined under oxidative stress. Plasma catechin concentrations and oxygen radical absorbance capacity (ORAC) values were determined. The CM produced with and without wine did not differ in their concentration of CD, LOOH and TBARS. Lag times of CM with and without wine were not significantly different, nor were the AUC. Plasma catechin values increased significantly after consumption of wine with the meal, whereas ORAC values did not. Conclusion Red wine consumption increases plasma catechins, but does not influence lipid peroxidation in postprandial CM.

This 8 week study examined whether a Mediterranean diet supplemented with red wine, had an acute impact on subjects diagnosed with the metabolic syndrome. Twelve non-smoking subjects with diagnostic criteria of the metabolic syndrome on minimal medication, consumed a Mediterranean-like diet for 4 weeks respectively without and with red wine. The amount of red wine consumed was 250 ml (26 grams of alcohol) per day for male and 180 ml (19 grams) per day for female participants. A nutrigenetic profile for cardiovascular risk factors was performed on each participant. Fasting blood specimens were taken at baseline, after the diet and after the diet with wine interventions for platelet function, procoagulants FVII and FVIII, von Willebrand’s factor, fibrinogen, tissue plasminogen activator, plasminogen activator inhibitor-1, highly sensitive C-reactive protein and oxygen radical absorbance capacity (ORAC). After both periods of diet without wine and with wine, ORAC increased significantly compared to baseline levels. Except for platelet H2O2 fluxes and FVII concentration, none of the haemostatic or inflammatory parameters changed significantly after the intervention periods compared with baseline levels. Genetic risk factors for cardiovascular disease were identified in all study participants and the potential genotypic effects relevant to this study were generally in agreement with expected phenotypic response following the dietary intervention. Our conclusions are that the period of intervention was too short for substantial changes in haemostatic or in inflammatory parameters in subjects who already manifest some changes in their cardiovascular system and who showed diverse genetic profiles underlying increased cardiovascular risk.