A Trial of the Effect of Micronutrient Supplementation on Treatment Outcome, T Cell Counts, Morbidity, and Mortality in Adults with Pulmonary Tuberculosis.

Tuberculosis (TB) often coincides with nutritional deficiencies. The effects of micronutrient supplementation on TB treatment outcomes, clinical complications, and mortality are uncertain. We conducted a randomized, double-blind, placebo-controlled trial of micronutrients (vitamins A, B complex, C, and E, as well as selenium) in Dar es Salaam, Tanzania. We enrolled 471 human immunodeficiency virus (HIV)-infected and 416 HIV-negative adults with pulmonary TB at the time of initiating chemotherapy and monitored them for a median of 43 months. Micronutrients decreased the risk ofTB recurrence by 45% overall (95% confidence interval [CI], 7% to 67%; P = .02) and by 63% in HIV-infected patients (95% CI, 8% to 85%; P = .02). There were no significant effects on mortality overall; however, we noted a marginally significant 64% reduction of deaths in HIV-negative subjects (95% CI, -14% to 88%; P = .08). Supplementation increased CD3+ and CD4+ cell counts and decreased the incidence of extrapulmonary TB and genital ulcers in HIV-negative patients. Micronutrients reduced the incidence of peripheral neuropathy by 57% (95% CI, 41% to 69%; P < .001), irrespective of HIV status. There were no significant effects on weight gain, body composition, anemia, or HIV load. Micronutrient supplementation could improve the outcome in patients undergoing TB chemotherapy in Tanzania

Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: A randomized controlled trial in non-obese humans

Calorie restriction (CR) inhibits inflammation and slows aging in many animal species, but in rodents housed in pathogen-free facilities, CR impairs immunity against certain pathogens. However, little is known about the effects of long-term moderate CR on immune function in humans. In this multi-center, randomized clinical trial to determine CR's effect on inflammation and cell-mediated immunity, 218 healthy non-obese adults (20-50 y), were assigned 25% CR (n=143) or an ad-libitum (AL) diet (n=75), and outcomes tested at baseline, 12, and 24 months of CR. CR induced a 10.4% weight loss over the 2-y period. Relative to AL group, CR reduced circulating inflammatory markers, including total WBC and lymphocyte counts, ICAM-1 and leptin. Serum CRP and TNF-α concentrations were about 40% and 50% lower in CR group, respectively. CR had no effect on the delayed-type hypersensitivity skin response or antibody response to vaccines, nor did it cause difference in clinically significant infections. In conclusion, long-term moderate CR without malnutrition induces a significant and persistent inhibition of inflammation without impairing key in vivo indicators of cell-mediated immunity. Given the established role of these pro-inflammatory molecules in the pathogenesis of multiple chronic diseases, these CR-induced adaptations suggest a shift toward a healthy phenotype

Effects of 2-year calorie restriction on circulating levels of IGF-1, IGF-binding proteins and cortisol in nonobese men and women: A randomized clinical trial

Young-onset calorie restriction (CR) in rodents decreases serum IGF-1 concentration and increases serum corticosterone levels, which have been hypothesized to play major roles in mediating its anticancer and anti-aging effects. However, little is known on the effects of CR on the IGF-1 system and cortisol in humans. To test the sustained effects of CR on these key hormonal adaptations, we performed a multicenter randomized trial of a 2-year 25% CR intervention in 218 nonobese (body mass index between 22 and 27.8 kg m(-2) ) young and middle-aged (20-50 years age range) men and women. Average CR during the first 6 months was 19.5 ± 0.8% and 9.1 ± 0.7% over the next 18 months of the study. Weight loss averaged 7.6 ± 0.3 kg over the 2-years period of which 71% was fat mass loss (P < 0.0001). Average CR during the CR caused a significant 21% increase in serum IGFBP-1 and a 42% reduction in IGF-1:IGFBP-1 ratio at 2 years (P < 0.008), but did not change IGF-1 and IGF-1:IGFBP-3 ratio levels. Serum cortisol concentrations were slightly but significantly increased by CR at 1 year only (P = 0.003). Calorie restriction had no effect on serum concentrations of PDGF-AB and TGFβ-1. We conclude, on the basis of the present and previous findings, that, in contrast to rodents, humans do not respond to CR with a decrease in serum IGF-1 concentration or with a sustained and biological relevant increase in serum cortisol. However, long-term CR in humans significantly and persistently increases serum IGFBP-1 concentration

Effect of Multivitamin Supplementation on Measles Vaccine Response among HIV-exposed Uninfected Tanzanian Infants.

Immunization and nutritional interventions are mainstays of child health programs in sub-Saharan Africa, yet few published data exist on their interactions. HIV-exposed (but uninfected) infants enrolled in a randomized placebo-controlled trial of multivitamin supplements (vitamins B complex, C, and E) conducted in Tanzania were sampled for an assessment of measles IgG quantity and avidity at 15 to 18 months. Infants were vaccinated between 8.5 and 12 months of age, and all mothers received high-dose multivitamins as the standard of care. Of 201 HIV-exposed infants who were enrolled, 138 (68.7%) were seropositive for measles. There were no effects of infant multivitamin supplementation on measles seroconversion proportions, IgG concentrations, or IgG avidity (P > 0.05). The measles seroconversion proportion was greater for HIV-exposed infants vaccinated at 10 to 11 months of age than for those vaccinated at 8.5 to 10 months (P = 0.032) and greater for infants whose mothers had a CD4 T-cell count of <200 cells/μl than for infants whose mothers had a CD4 T-cell count of >350 cells/μl (P = 0.039). Stunted infants had a significantly decreased IgG quantity compared to nonstunted infants (P = 0.012). As for measles avidity, HIV-exposed infants vaccinated at 10 to 11 months had increased antibody avidity compared to those vaccinated at 8.5 to 10 months (P = 0.031). Maternal CD4 T-cell counts of <200 cells/μl were associated with decreased avidity compared to counts of >350 cells/μl (P = 0.047), as were lower infant height-for-age z-scores (P = 0.016). Supplementation with multivitamins containing B complex, C, and E does not appear to improve measles vaccine responses for HIV-exposed infants. Studies are needed to better characterize the impact of maternal HIV disease severity on the immune system development of HIV-exposed infants and the effect of malnutrition interventions on vaccine responses. (This study has been registered at ClinicalTrials.gov under registration no. NCT00197730.)

Perspective: Role of Micronutrients and Omega-3 Long-Chain Polyunsaturated Fatty Acids for Immune Outcomes of Relevance to Infections in Older Adults:A Narrative Review and Call for Action

The immune system is weakened by advancing age, often referred to as immunosenescence, increasing the vulnerability to, and frequently the severity of, infectious diseases in older people. This has become very apparent in the current coronavirus disease 2019 (COVID-19) pandemic for which older people are at higher risk of severe outcomes, even those who are fully vaccinated. Aging affects both the innate and adaptive immune systems and is characterized by an imbalanced inflammatory response. Increasing evidence shows that optimal status of nutrients such as vitamins C, D, and E and selenium and zinc as well as the omega-3 (n-3) fatty acids DHA and EPA can help compensate for these age-related changes. While inadequate intakes of these nutrients are widespread in the general population, this is often more pronounced in older people. Maintaining adequate intakes is a challenge for them due to a range of factors such as physical, physiological, and cognitive changes; altered absorption; and the presence of noncommunicable diseases. While nutritional requirements are ideally covered by a balanced diet, this can be difficult to achieve, particularly for older people. Fortified foods and nutritional complements are effective in achieving adequate micronutrient intakes and should be considered as a safe and cost-effective means for older people to improve their nutritional status and hence support their defense against infections. Complementing the diet with a combination of micronutrients, particularly those playing a key role in the immune system such as vitamins C, D, and E and selenium and zinc as well as DHA and EPA, is recommended for older people. Optimal nutrition to support the immune system in older people will remain essential, particularly in the face of the current COVID-19 pandemic and, thus, developing strategies to ensure adequate nutrition for the growing number of older adults will be an important and cost-effective investment in the future

A Trial of the Effect of Micronutrient Supplementation on Treatment Outcome, T Cell Counts, Morbidity, and Mortality in Adults with Pulmonary Tuberculosis

Background Tuberculosis (TB) often coincides with nutritional deficiencies. The effects of micronutrient supplementation on TB treatment outcomes, clinical complications, and mortality are uncertain. Methods We conducted a randomized, double-blind, placebo-controlled trial of micronutrients (vitamins A, B complex, C, and E, as well as selenium) in Dar es Salaam, Tanzania. We enrolled 471 human immunodeficiency virus (HIV)–infected and 416 HIV-negative adults with pulmonary TB at the time of initiating chemotherapy and monitored them for a median of 43 months. Results Micronutrients decreased the risk of TB recurrence by 45% overall (95% confidence interval [CI], 7% to 67%; P = .02) and by 63% in HIV-infected patients (95% CI, 8% to 85%; P = .02). There were no significant effects on mortality overall; however, we noted a marginally significant 64% reduction of deaths in HIV-negative subjects (95% CI, −14% to 88%; P = .08). Supplementation increased CD3+ and CD4+ cell counts and decreased the incidence of extrapulmonary TB and genital ulcers in HIV-negative patients. Micronutrients reduced the incidence of peripheral neuropathy by 57% (95% CI, 41% to 69%; P < .001), irrespective of HIV status. There were no significant effects on weight gain, body composition, anemia, or HIV load. Conclusions Micronutrient supplementation could improve the outcome in patients undergoing TB chemotherapy in Tanzania

Consensus statement immunonutrition and exercise

In this consensus statement on immunonutrition and exercise, a panel of knowledgeable contributors from across the globe provides a consensus of updated science, including the background, the aspects for which a consensus actually exists, the controversies and, when possible, suggested directions for future research