Vitamin A in resistance to and recovery from infection: relevance to SARS-CoV2.

SARS-CoV2 infects respiratory epithelial cells via its cellular receptor angiotensin-converting enzyme 2, causing a viral pneumonia with pronounced inflammation resulting in significant damage to the lungs and other organ systems, including the kidneys, though symptoms and disease severity are quite variable depending on the intensity of exposure and presence of underlying conditions that may affect the immune response. The resulting disease, coronavirus disease 2019 (COVID-19), can cause multi-organ system dysfunction in patients requiring hospitalisation and intensive care treatment. Serious infections like COVID-19 often negatively affect nutritional status, and the resulting nutritional deficiencies may increase disease severity and impair recovery. One example is the viral infection measles, where associated vitamin A (VA) deficiency increases disease severity and appropriately timed supplementation during recovery reduces mortality and hastens recovery. VA may play a similar role in COVID-19. First, VA is important in maintaining innate and adaptive immunity to promote clearance of a primary infection as well as minimise risks from secondary infections. Second, VA plays a unique role in the respiratory tract, minimising damaging inflammation, supporting repair of respiratory epithelium and preventing fibrosis. Third, VA deficiency may develop during COVID-19 due to specific effects on lung and liver stores caused by inflammation and impaired kidney function, suggesting that supplements may be needed to restore adequate status. Fourth, VA supplementation may counteract adverse effects of SARS-CoV2 on the angiotensin system as well as minimises adverse effects of some COVID-19 therapies. Evaluating interactions of SARS-CoV2 infection with VA metabolism may thus provide improved COVID-19 therapy.

Two common single nucleotide polymorphisms in the gene encoding beta-carotene 15,15'-monoxygenase alter beta-carotene metabolism in female volunteers.

The key enzyme responsible for beta-carotene conversion into retinal is beta-carotene 15,15'-monoxygenase (BCMO1). Since it has been reported that the conversion of beta-carotene into vitamin A is highly variable in up to 45% of healthy individuals, we hypothesized that genetic polymorphisms in the BCMO1 gene could contribute to the occurrence of the poor converter phenotype. Here we describe the screening of the total open reading frame of the BCMO1 coding region that led to the identification of two common nonsynonymous single nucleotide polymorphisms (R267S: rs12934922; A379V: rs7501331) with variant allele frequencies of 42 and 24%, respectively. In vitro biochemical characterization of the recombinant 267S + 379V double mutant revealed a reduced catalytic activity of BCMO1 by 57% (P<0.001). Assessment of the responsiveness to a pharmacological dose of beta-carotene in female volunteers confirmed that carriers of both the 379V and 267S + 379V variant alleles had a reduced ability to convert beta-carotene, as indicated through reduced retinyl palmitate:beta-carotene ratios in the triglyceride-rich lipoprotein fraction [-32% (P=0.005) and -69% (P=0.001), respectively] and increased fasting beta-carotene concentrations [+160% (P=0.025) and +240% (P=0.041), respectively]. Our data show that there is genetic variability in beta-carotene metabolism and may provide an explanation for the molecular basis of the poor converter phenotype within the population.

Comparison of the effects of supplemental red palm oil and sunflower oil on maternal vitamin A status.

BACKGROUND: Conflicting results have been reported on the ability of dietary carotenoids to improve vitamin A status in lactating women. Red palm oil is one of the richest dietary sources of beta-carotene. OBJECTIVE: We aimed to determine the efficacy of red palm oil in increasing retinol and provitamin A status in pregnant and lactating women. DESIGN: Ninety rural, pregnant Tanzanian women from 3 randomly selected villages were recruited during their third trimester to participate in 3 dietary intervention groups: a control group, who were encouraged to maintain the traditional practice of eating staples with dark-green leafy vegetables, and 2 study groups, who were given either sunflower or red palm oil for use in household food preparations. The intervention lasted 6 mo. Plasma samples were collected at the third trimester and 1 and 3 mo postpartum, and breast-milk samples were collected 1 and 3 mo postpartum. RESULTS: Supplementation with red palm oil, which is rich in provitamin A, increased alpha- and beta-carotene concentrations significantly (P < 0.001) in both plasma and breast milk. Plasma retinol concentrations were similar in all dietary groups. Breast-milk retinol concentrations tended to decrease from 1 to 3 mo postpartum in the control group, but were maintained in both oil groups. The difference in change in breast-milk retinol concentration between the red palm oil group and the control group was significant (P = 0.041). CONCLUSIONS: Consumption of red palm oil increases concentrations of alpha- and beta-carotene in both breast milk and serum and maintains breast-milk retinol concentrations. Sunflower oil consumption seems to conserve breast-milk retinol similarly to consumption of red palm oil. Breast-milk retinol might be maintained through increased dietary intake of these vegetable oils and use of mild cooking preparation methods (such as the addition of oil at the end of cooking and avoidance of frying).

Short-term effects of dietary sodium intake on bone metabolism in postmenopausal women measured using urinary deoxypyridinoline excretion.

The influence of Na load on bone metabolism was investigated in postmenopausal women using urinary deoxypyridinoline (DPD) as a marker of bone resorption. In a cross-over study, fourteen postmenopausal women were divided into two groups of seven. A fixed diet providing 816 mg Ca/d with either 60 or 170 mmol Na/d was consumed. At the end of an 8 d period the groups switched diets for a further 8 d period. Urine was collected daily for the last 4 d of each period. There was no significant difference in DPD excretion between high-Na and low-Na diets (129 nmol/d v. 132 nmol/d; P = 0.18). There was, however, a significant relationship (P = 0.02) between the changes in DPD excretion and urinary Ca. Plasma Mg fell from 0.83 to 0.81 mmol/l on the high Na intake (P < 0.001), but there was no significant effect on plasma Ca or intact parathyroid hormone levels. It is concluded that varying dietary Na intake may affect Ca and Mg metabolism, but we were unable to demonstrate an effect on bone resorption at the levels of intake used.

Milk cytokines and subclinical breast inflammation in Tanzanian women: effects of dietary red palm oil or sunflower oil supplementation.

Previously, we have found that subclinical breast inflammation, as indicated by raised breastmilk concentrations of sodium and the inflammatory cytokine, interleukin-8 (IL-8), was highly prevalent in Bangladesh and associated with poor infant growth. In order to investigate further the prevalence of subclinical breast inflammation and to assess the impact of dietary intervention, we studied rural Tanzanian women taking part in a study of dietary sunflower or red palm oil supplementation during late pregnancy and lactation. We measured breastmilk concentrations of IL-8, the anti-inflammatory cytokine, transforming growth factor-beta2 (TGF-beta) and the ratio of sodium to potassium. We also estimated systemic inflammation by plasma concentrations of the acute phase proteins, alpha1-acid glycoprotein and C-reactive protein. There were highly significant intercorrelations among milk Na/K ratio and concentrations of IL-8 and TGF-beta, the last only after treatment with bile salts which also improved TGF-beta recovery in the enzyme-linked immunosorbent assay (ELISA). Plasma acute phase protein concentrations tended to correlate with milk Na/K ratio and IL-8, suggesting that subclinical breast inflammation was related to systemic inflammation. Dietary supplementation with vitamin E-rich sunflower oil but not provitamin A-containing red palm oil decreased milk Na/K, IL-8 and TGF-beta at 3 months postpartum; however, the effect was significant only for Na/K ratio. The results suggest that milk Na/K ratio, IL-8, and TGF-beta all measure the same phenomenon of subclinical breast inflammation but that Na/K ratio, having the lowest assay variability, is the most useful. Subclinical breast inflammation may result in part from systemic inflammation and may be improved by increased dietary intake of vitamin E-rich sunflower oil.