Adjunct n-3 Long-Chain Polyunsaturated Fatty Acid Treatment in Tuberculosis Reduces Inflammation and Improves Anemia of Infection More in C3HeB/FeJ Mice With Low n-3 Fatty Acid Status Than Sufficient n-3 Fatty Acid Status.

Populations at risk for tuberculosis (TB) may have a low n-3 polyunsaturated fatty acid (PUFA) status. Our research previously showed that post-infection supplementation of n-3 long-chain PUFA (LCPUFA) in TB without TB medication was beneficial in n-3 PUFA sufficient but not in low-status C3HeB/FeJ mice. In this study, we investigated the effect of n-3 LCPUFA adjunct to TB medication in TB mice with a low compared to a sufficient n-3 PUFA status. Mice were conditioned on an n-3 PUFA-deficient (n-3FAD) or n-3 PUFA-sufficient (n-3FAS) diet for 6 weeks before TB infection. Post-infection at 2 weeks, both groups were switched to an n-3 LCPUFA [eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA)] supplemented diet and euthanized at 4- and 14- days post-treatment. Iron and anemia status, bacterial loads, lung pathology, lung cytokines/chemokines, and lung lipid mediators were measured. Following 14 days of treatment, hemoglobin (Hb) was higher in the n-3FAD than the untreated n-3FAS group (p = 0.022), whereas the n-3FAS (drug) treated control and n-3FAS groups were not. Pro-inflammatory lung cytokines; interleukin-6 (IL-6) (p = 0.011), IL-1α (p = 0.039), MCP1 (p = 0.003), MIP1- α (p = 0.043), and RANTES (p = 0.034); were lower, and the anti-inflammatory cytokine IL-4 (p = 0.002) and growth factor GMCSF (p = 0.007) were higher in the n-3FAD compared with the n-3FAS mice after 14 days. These results suggest that n-3 LCPUFA therapy in TB-infected mice, in combination with TB medication, may improve anemia of infection more in low n-3 fatty acid status than sufficient status mice. Furthermore, the low n-3 fatty acid status TB mice supplemented with n-3 LCPUFA showed comparatively lower cytokine-mediated inflammation despite presenting with lower pro-resolving lipid mediators.

Beneficial effect of long-chain n-3 polyunsaturated fatty acid supplementation on tuberculosis in mice.

Intakes of the omega-3 essential fatty acids (n-3 EFAs) are low in the general adult population, with high n-6/n-3 polyunsaturated fatty acid (PUFA) ratios and the accompanying suboptimal n-3 PUFA status. Eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) have antibacterial and inflammation-resolving effects in tuberculosis (TB). However, whether switching to a diet with optimum n-3 EFA intake after the infection has comparable benefits has not been investigated. We aimed to compare the effects of a diet with sufficient n-3 EFA content in an acceptable n-6/n-3 PUFA ratio for rodents ((n-3)eFAS group) with those on the same diet supplemented with EPA and DHA (EPA/DHA group) in Mycobacterium tuberculosis (Mtb)-infected C3HeB/FeJ mice with a low n-3 PUFA status. Mice were conditioned on an n-3 PUFA-deficient diet with a high n-6/n-3 PUFA ratio for 6 weeks before Mtb infection and randomized to either (n-3)eFAS or EPA/DHA diets 1 week post-infection for 3 weeks. At endpoint, EPA and DHA compositions were higher and arachidonic acid, osbond acid, and total n-6 LCPUFAs lower in all lipid pools measured in the EPA/DHA group (all P < 0.001). Percentage body weight gain was higher (P = 0.017) and lung bacterial load lower (P < 0.001) in the EPA/DHA group. Additionally, the EPA/DHA group had a more pro-resolving lung lipid mediator profile and lower lung in IL-1α and IL-1ß concentrations (P = 0.023, P = 0.049). Inverse correlations were found between the lung and peripheral blood mononuclear cell EPA and DHA and selected pro-inflammatory cytokines. These are the first findings that indicate that EPA/DHA supplementation provides benefits superior to a diet with sufficient n-3 EFAs concerning bacterial killing, weight gain and lung inflammation resolution in Mtb-infected mice with a low n-3 PUFA status. Therefore, EPA and DHA may be worth considering as adjunct TB treatment.

Longer-Term Omega-3 LCPUFA More Effective Adjunct Therapy for Tuberculosis Than Ibuprofen in a C3HeB/FeJ Tuberculosis Mouse Model.

Advancement in the understanding of inflammation regulation during tuberculosis (TB) treatment has led to novel therapeutic approaches being proposed. The use of immune mediators like anti-inflammatory and pro-resolving molecules for such, merits attention. Drug repurposing is a widely used strategy that seeks to identify new targets to treat or manage diseases. The widely explored nonsteroidal anti-inflammatory drug (NSAID) ibuprofen and a more recently explored pharmaconutrition therapy using omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs), have the potential to modulate the immune system and are thus considered potential repurposed drugs in this context. These approaches may be beneficial as supportive therapy to the already existing treatment regimen to improve clinical outcomes. Here, we applied adjunct ibuprofen and n-3 LCPUFA therapy, respectively, with standard anti-TB treatment, in a C3HeB/FeJ murine model of TB. Bacterial loads, lung pathology, lung cytokines/chemokines and lung lipid mediators were measured as outcomes. Lung bacterial load on day 14 post-treatment (PT) was lower in the n-3 LCPUFA, compared to the ibuprofen group (p = 0.039), but was higher in the ibuprofen group than the treated control group (p = 0.0315). Treated control and ibuprofen groups had more free alveolar space initially as compared to the n-3 LCPUFA group (4 days PT, p= 0.0114 and p= 0.002, respectively); however, significantly more alveolar space was present in the n-3 LCPUFA group as compared to the ibuprofen group by end of treatment (14 days PT, p = 0.035). Interleukin 6 (IL-6) was lower in the ibuprofen group as compared to the treated control, EPA/DHA and untreated control groups at 4 days PT (p = 0.019, p = 0.019 and p = 0.002, respectively). Importantly, pro-resolving EPA derived 9-HEPE, 11-HEPE, 12-HEPE and 18-HEPE lipid mediators (LMs) were significantly higher in the EPA/DHA group as compared to the ibuprofen and treated control groups. This suggests that n-3 LCPUFAs do improve pro-resolving and anti-inflammatory properties in TB, and it may be safe and effective to co-administer as adjunct therapy with standard TB treatment, particularly longer-term. Also, our results show host benefits upon short-term co-administration of ibuprofen, but not throughout the entire TB treatment course.

Omega-3 Fatty Acid and Iron Supplementation Alone, but Not in Combination, Lower Inflammation and Anemia of Infection in Mycobacterium tuberculosis-Infected Mice.

Progressive inflammation and anemia are common in tuberculosis (TB) and linked to poor clinical outcomes. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have inflammation-resolving properties, whereas iron supplementation in TB may have limited efficacy and enhance bacterial growth. We investigated effects of iron and EPA/DHA supplementation, alone and in combination, on inflammation, anemia, iron status markers and clinical outcomes in Mycobacterium tuberculosis-infected C3HeB/FeJ mice. One week post-infection, mice received the AIN-93 diet without (control) or with supplemental iron (Fe), EPA/DHA, or Fe+EPA/DHA for 3 weeks. Mice supplemented with Fe or EPA/DHA had lower soluble transferrin receptor, ferritin and hepcidin than controls, but these effects were attenuated in Fe+EPA/DHA mice. EPA/DHA increased inflammation-resolving lipid mediators and lowered lung IL-1α, IFN-γ, plasma IL-1ß, and TNF-α. Fe lowered lung IL-1α, IL-1ß, plasma IL-1ß, TNF-α, and IL-6. However, the cytokine-lowering effects in the lungs were attenuated with Fe+EPA/DHA. Mice supplemented with EPA/DHA had lower lung bacterial loads than controls, but this effect was attenuated in Fe+EPA/DHA mice. Thus, individually, post-infection EPA/DHA and iron supplementation lowered systemic and lung inflammation and mitigated anemia of infection in TB, but not when combined. EPA/DHA also enhanced bactericidal effects and could support inflammation resolution and management of anemia.

The Problem of Hospital Malnutrition in the African Continent.

This study aims to determine the prevalence of risk of malnutrition on admission and discharge in African hospitals, and to identify the association with selected indicators. In this multi-center prospective cohort study, adult patients from hospitals in South Africa, Kenya, and Ghana were screened on admission and discharge and contacted 3 months post-discharge. Relevant morbidity and mortality outcomes were assessed. At risk of malnutrition was indicated if NRS-2002 score ≥3. Adult patients (n = 2126; 43.11 years, IQR: 31.95-55.60; 52.2% female) were screened on admission and 61% were identified as at risk of malnutrition. The proportion of at-risk patients for the three hospitals in Kenya and Ghana (66.2%) were significantly higher than that of the three South African hospitals (53.7%) (Chi2 = 31.0; p < 0.001). Discharge risk of malnutrition was 71.2% (n = 394). Mean length of stay (LOS) was 6.46 ± 5.63 days. During hospitalization, 20.6% lost ≥5% body weight, 18.8% were referred for nutrition support, and discharge BMI (23.87 ± 7.38 kg/m2) was significantly lower than admission BMI (24.3 ± 7.3 kg/m2) (p < 0.001). Admission nutrition risk was associated with lower admission and discharge BMI (p < 0.001), longer LOS (p < 0.001), increased 3-month re-admission rates (Chi2 = 1.35; p = 0.245) and increased mortality (Chi2 = 21.68; p < 0.001). Nearly two-thirds of patients were at risk of malnutrition on admission. This was associated with longer LOS and greater hospital mortality. The nutritional status of patients deteriorated during hospitalization. Routine screening practices with appropriate nutrition support action should be implemented as a matter of urgency.

Stakeholder Attitudes towards Donating and Utilizing Donated Human Breastmilk.

The promotion and support of human milk banks (HMBs) can enhance exclusive breastfeeding rates. The success and sustainability of HMBs depend on the support from relevant healthcare workers and related communities. This study aimed to determine attitudes of key stakeholders, including mothers, healthcare workers and grandmothers, regarding the donation and receipt of human breastmilk. This study was conducted at a public hospital and clinics in the North West Province, South Africa. Eight focus group discussions explored the attitudes regarding donating and receiving human breastmilk: three groups with mothers of infants (n = 13), three with grandmothers (>60 years old) (n = 17) and two with healthcare professionals working with infants (n = 11). Four main themes emerged: perception regarding breast and formula feeding; exposure to the concept of "wet nursing"; breastmilk donation; and utilization and opinions of community members and traditional healers. Specific barriers identified included the processes for donating and receiving milk, safety, human immuno-deficiency virus (HIV) screening and cultural beliefs. Mothers' fears included having insufficient milk for their own infants, changes in the quality of donated milk during pasteurization and transportation and HIV transmission. Despite barriers towards donations to and the use of HMBs, sufficient information could enhance donations by mothers and breastmilk utilization.

Interactions between C-reactive protein genotypes with markers of nutritional status in relation to inflammation.

Inflammation, as indicated by C-reactive protein concentrations (CRP), is a risk factor for chronic diseases. Both genetic and environmental factors affect susceptibility to inflammation. As dietary interventions can influence inflammatory status, we hypothesized that dietary effects could be influenced by interactions with single nucleotide polymorphisms (SNPs) in the CRP gene. We determined 12 CRP SNPs, as well as various nutrition status markers in 2010 black South Africans and analyzed their effect on CRP. Interactions were observed for several genotypes with obesity in determining CRP. Lipid intake modulated the pro-inflammatory effects of some SNPs, i.e., an increase in both saturated fatty acid and monounsaturated fatty acid intake in those homozygous for the polymorphic allele at rs2808630 was associated with a larger increase in CRP. Those harboring the minor alleles at rs3093058 and rs3093062 presented with significantly higher CRP in the presence of increased triglyceride or cholesterol intake. When harboring the minor allele of these SNPs, a high omega-6 to -3 ratio was, however, found to be anti-inflammatory. Carbohydrate intake also modulated CRP SNPs, as HbA1C and fasting glucose levels interacted with some SNPs to influence the CRP. This investigation highlights the impact that nutritional status can have on reducing the inherent genetic susceptibility to a heightened systemic inflammatory state.

The use of predefined diet quality scores in the context of CVD risk during urbanization in the South African Prospective Urban and Rural Epidemiological (PURE) study.

OBJECTIVE: Urbanization is generally associated with increased CVD risk and accompanying dietary changes. Little is known regarding the association between increased CVD risk and dietary changes using approaches such as diet quality. The relevance of predefined diet quality scores (DQS) in non-Western developing countries has not yet been established. DESIGN: The association between dietary intakes and CVD risk factors was investigated using two DQS, adapted to the black South African diet. Dietary intake data were collected using a quantitative FFQ. CVD risk was determined by analysing known CVD risk factors. SETTING: Urban and rural areas in North West Province, South Africa. SUBJECTS: Apparently healthy volunteers from the South African Prospective Urban and Rural Epidemiological (PURE) study population (n 1710). RESULTS: CVD risk factors were significantly increased in the urban participants, especially women. Urban men and women had significantly higher intakes of both macro- and micronutrients with macronutrient intakes well within the recommended CVD guidelines. While micronutrient intakes were generally higher in the urban groups than in the rural groups, intakes of selected micronutrients were low in both groups. Both DQS indicated improved diet quality in the urban groups and good agreement was shown between the scores, although they seemed to measure different aspects of diet quality. CONCLUSIONS: The apparent paradox between improved diet quality and increased CVD risk in the urban groups can be explained when interpreting the cut-offs used in the scores against the absolute intakes of individual nutrients. Predefined DQS as well as current guidelines for CVD prevention should be interpreted with caution in non-Western developing countries.

Beliefs of South Africans regarding food and cardiovascular health.

OBJECTIVES: To investigate the beliefs of South African metropolitan adults regarding the importance of influencing cardiovascular health by eating certain food types, and to compare these beliefs between different race, living standards, age and gender groups. DESIGN: Randomised cross-sectional study. Trained fieldworkers administered questionnaires by conducting face-to-face interviews with consumers. SUBJECTS: Two thousand South Africans (16 years and older) were randomly selected from metropolitan areas in South Africa. The data were weighted to be representative of the total South African metropolitan population (N = 10695000) based on gender, age and race distribution. RESULTS: The majority (94%) of the population indicated that it is important to influence cardiovascular risk-related health issues by eating certain food types, especially the higher LSM (Living Standard Measure) groups within the different race groups. Weight loss was considered the least important (61% indicated that it is important) compared with cholesterol lowering (80%), blood pressure (89%), diabetes (86%) and healthy blood vessels (89%). In the higher LSM groups (7-10) higher proportions of respondents agreed than in the lower LSM groups (2 and 3). No differences were seen in responses between different gender, race and age groups. CONCLUSIONS AND RECOMMENDATIONS: This study shows that the metropolitan South African adult population considers the influence on cardiovascular health by eating certain food types to be important. However, modifying weight loss by eating certain food types was considered less important.