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The cholesterol-raising properties of the apolipoprotein E (APOE) epsilon-4 (ε-4) allele has been validated in the South African population. Mounting evidence supports the added value of APOE genotyping for the evaluation of cardiovascular risk in dyslipidemic patients beyond its established role in the diagnosis of late-onset Alzheimer's disease (AD). The aim of this study was to determine the potential benefits of combining AD family history with questionnaire-based lifestyle assessment to facilitate the clinical interpretation of APOE genotyping results. A total of 580 unrelated South African individuals prospectively enrolled in a chronic disease screening program incorporating a genetic component (2010-2015) was selected for inclusion in this study based on the presence (75) or absence (505) of AD family history. Biochemical assessment of their lipid profiles was performed according to standard laboratory protocols. All study participants were genotyped for the APOE ε-2/ε-3/ε-4 alleles using allele-specific TaqMan real-time polymerase chain reaction technology. In patients without a family history of AD, APOE genotype modified the relationship between alcohol intake and body mass index (p = 0.026), with a significant positive correlation noted between these parameters being limited to ε-4 allele carriers. APOE genotype also modified the association between alcohol intake and total serum cholesterol in patients with a positive family history of AD (p = 0.026). We demonstrated the benefits of a questionnaire-based approach for assessment of lifestyle risk factors to facilitate clinical interpretation of APOE genotyping results for targeted intervention in a genetic subgroup of dyslipidemic patients at increased risk for AD.

Integrative Medicine is defined as a post-modern healing-oriented medicine that reaffirms the importance of the relationship between practitioner and patient. All appropriate therapeutic approaches, both conventional and alternative/complimentary informed by evidence are explored with a focus on the whole person (body, mind and spirit). To achieve optimal health the principles of Functional Medicine needs to be applied to address the underlying causes of disease, using a systems-oriented approach and engaging both patient and practitioner in a therapeutic partnership [1]. In the South African context Integrative Medicine includes modern Western (allopathic) medicine, various recognized alternative and complementary models, traditional healers, lifestyle medicine, functional medicine, and the therapeutic doctor/patient relationship. Integrative healthcare services demand interprofessional collaboration between bio-medically trained doctors and traditional, complementary and alternative practitioners to facilitate the process. The main reason for developing integrative healthcare was the increased demand for holistic care from patients. The doctor is expected to provide care that is patient-centered and comprehensive by incorporating high-tech genomic information, systems biology, and functional medicine into routine clinical practice. The doctor of the future will become an integrative healer whose practice differs in many ways from that of today’s typical physician. Patients will increasingly take responsibility for their own health, with medical care focused more extensively on preventing disease and injury.

Alcohol intake is associated with variation in many biochemical markers and metabolic processes implicated in car- diovascular disease (CVD) and other non-communicable diseases associated with advanced aging. Some changes are beneficial, while others may be harmful in relation to individual differences in genetic background. The objective of this study was to compare the effects of alternative moderate consumption of red wine and brandy on the lipid profile in the same experimental population of healthy adults and to identify genetic risk factors that may contribute to differences in response. An 8-week ran- domised crossover intervention study of red wine versus brandy consumption was performed in 37 healthy volunteers (19 males and 18 females) between the ages of 26 and 71 years. The assessments included anthropometric measurements, biochemical determinations and genetic analysis using a multi-gene CVD test. The level of total glutathione as an indicator of antioxidant capacity was significantly decreased only after the brandy intervention when compared to the baseline (p = 0.002). Both the brandy and wine intervention resulted in a significant increase in HDL-cholesterol (p < 0.001). Significant differential effects were shown in relation to genetic variation in the APOE (p = 0.027) and MTHFR (p = 0.048) genes, known to be associated with hyper-responsiveness to alcohol intake. Novel findings included a statistically significant increase of both total cholesterol (p = 0.016) and triglyceride (p = 0.022) levels with alcohol intake only in individuals who tested positive for the low-penetrance H63D and/or C282Y mutations in the HFE gene. This study confirmed the well-established protective effect of moderate alcohol consumption on the lipid profile, especially red wine. Since the genetic background influences the effect of alcohol on biochemical parameters of CVD risk, safe limits of wine and brandy consumption may in future be based partly on the genetic profile.

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.

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.

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.