Vitamin D deficiency is associated with higher risks for SARS-CoV-2 infection and COVID-19 severity: a retrospective case-control study.

Robust evidence of whether vitamin D deficiency is associated with COVID-19 infection and its severity is still lacking. The aim of the study was to evaluate the association between vitamin D levels and the risks of SARS-CoV-2 infection and severe disease in those infected. A retrospective study was carried out among members of Clalit Health Services (CHS), the largest healthcare organization in Israel, between March 1 and October 31, 2020. We created two matched case-control groups of individuals for which vitamin D levels and body mass index (BMI) were available before the pandemic: group (A), in which 41,757 individuals with positive SARS-CoV-2 PCR tests were matched with 417,570 control individuals without evidence of infection, and group (B), in which 2533 patients hospitalized in severe condition for COVID-19 were matched with 2533 patients who were tested positive for SARS-CoV-2, but were not hospitalized. Conditional logistic models were fitted in each of the groups to assess the association between vitamin D levels and outcome. An inverse correlation was demonstrated between the level of vitamin D and the risks of SARS-CoV-2 infection and of severe disease in those infected. Patients with very low vitamin D levels (< 30 nmol/L) had the highest risks for SARS-CoV-2 infection and also for severe COVID-19 when infected-OR 1.246 [95% CI 1.210-1.304] and 1.513 [95% CI 1.230-1.861], respectively. In this large observational population study, we show a significant association between vitamin D deficiency and the risks of SARS-CoV-2 infection and of severe disease in those infected.

Moderate 'multivitamin' supplementation improved folate and vitamin B12 status in the elderly.

The dependent elderly are widely considered to be at higher risk of nutritional problems. Suboptimal micronutrient intake might put the elderly, especially those living in nursing homes, at high risk of morbidity. So far, no public authority, except for the Israel Ministry of Health, has issued particular recommendations for micronutrient supplementation for the elderly. We hypothesized that moderate 'multivitamin' supplementation could improve the vitamin status of the dependent elderly. The study took place in two nursing homes and included 144 dependent elderly (males/females, 35/109). Demographic and clinical data as well as routine blood tests were retrieved from the patient electronic medical records. After a two-year daily 'multivitamin' supplementation, containing 120µg of folic acid, there was a small and non-significant increase of 12% in serum folate; the same 'multivitamin' preparatory, containing 2.4µg of vitamin B12, significantly increased serum vitamin B12 by 8%. Three models of evaluation clearly showed the effect of a two- year vitamin supplementation: 1. The number of subjects with the lowest baseline concentration range, decreased, with moderate concentration, increased, with no difference at the higher concentrations; 2. Above each vitamin concentration, the number of subjects was higher than at baseline; 3. The two vitamins at the two lower concentration tertiles increased, and at the highest tertile, folate was not affected, whereas vitamin B12 decreased. Therefore, very moderate 'multivitamin' supplementation, as practiced in our study, has a high probability of improving vulnerable old population health status without causing any adverse effects to others.

Hair for brain trade-off, a metabolic bypass for encephalization.

Hair loss in humans is perplexing and raises many hypothetical explanations. This paper suggests that hair loss in humans is metabolically related to encephalization; and that hair covered hominids would have been unable to evolve large brains because of a dietary restriction of several amino acids which are essential for hair and brain development. We use simulations to imply that hair loss must have preceded increase in brain size & volume. In this respect we see hair loss as a major force in human evolution. We assume that hair reduction required favorable climatic conditions and must have been quick. Using evolutionary and ecological time scales, we pinpoint hair loss to a period around 2.2-2.4 million years ago. The dating is further supported by a rapid selection at that time of the sialic acid deletion mutation which may have protected growing human brains against calcium ion flux. In summary we view encephalization, in part, as a metabolic trade-off between hair and brain. Other biochemical changes may have intervened in the process too; and the deletion mutation of sialic acid hydroxylation may have been involved as well.

Vitamins in the prevention or delay of cognitive disability of aging.

During the 20th century, the average lifespan in the industrialized societies has enormously increased and it is still rising. With the increase in the number of old people, a parallel increase in the number of the disabled elderly is postulated. Thus, the whole society might suffer from an imbalance between the productive segment of the society and a huge segment of helpless people. Moderation of the physiological processes, which enhance disability in aging, turns out to be a major concern in health research and clinical practice. Preservation of brain integrity, which is partly influenced by nutrition, presumably is the main target in the attempt to delay the development of disability of aging. Optimal micronutrient status would moderate the deterioration in brain integrity. The human brain is probably the most vulnerable tissue affected by a long-term unbalanced nutrition and is particularly vulnerable to reactive oxygen species and to oxidative stress, because of its high oxygen requirement, its iron storage capacity and its elevated polyunsaturated fatty acid content, and because of its low synthesis capacity of endogenous antioxidants. The capability of central nervous system (CNS) cells to regenerate is most limited, because their repair is inhibited by anti-apoptotic molecules. Efficient autophagy is the major mechanism that moderates accumulation of aggregating compounds. Autophagy is probably a crucial and a major process in the preservation of brain integrity. Micronutrients (vitamins, trace-elements and also antioxidants) most likely affect brain integrity by normalizing efficient autophagy. Brain sensitivity to metabolic disorders is demonstrated by the effect of homocysteine on metabolic pathways, on brain integrity and on the cognitive capacity. Brain imaging might be used as a surrogate for detecting long-lasting low status of micronutrients. Comprehensive evaluation of brain scans concomitantly with blood micronutrient examinations may provide reliable criteria for the estimation of the optimal micronutrient intakes or blood concentrations. Recommended dietary intakes for micronutrients are based on a list of biomarkers, but have not been suggested a safe range for their intake or blood concentration. According to many studies, a U-shaped curve prevails for the effect of serum calcidiol concentration on the relative risk of morbidity and mortality. An increased relative risk of morbidity and mortality with lower serum calcidiol has been shown in almost all the studies. A safe range of 20-40 ng/mL was identified for serum calcidiol. A significant detrimental effect of serum calcidiol on the hazard ratio for the combined data of all-cause mortality and acute coronary syndrome morbidity was shown at a concentration higher than 36 ng/ml. Most of the tolerable upper intake levels for the micronutrients, published by authorized institutions, were set without considering the long-term effects of overdosing. Excessive intake of almost all the micromutrients, particularly for a long period of time, produces adverse effects. In most of the elderly people prevail an insufficient intake of one or more micronutruients. Therefore, until an efficient laboratory system for evaluating blood levels is established, a moderate 'multivitamin' supplementation at an amount of about half the American RDA for most of the micronutrients is suggested.

Vitamin D levels for preventing acute coronary syndrome and mortality: evidence of a nonlinear association.

CONTEXT: Low serum calcidiol has been associated with multiple comorbidities and mortality but no "safe" range has been found for the upper concentration. OBJECTIVE: We aim to establish the upper threshold of serum calcidiol, beyond which there is an increased risk for acute coronary syndrome and/or mortality. DESIGN, SETTING, AND PARTICIPANTS: We extracted data for 1,282,822 Clalit Health Services members aged >45 between July 2007 and December 2011. Records of mortality or acute coronary syndrome were extracted during the follow-up period. Kaplan-Meier analysis calculated time to episode and Cox regression models generated adjusted hazard ratios for episode by calcidiol group (<10, 10.1-20, 20.1-36, and >36.1 ng/mL). OUTCOME MEASURES: Acute coronary syndrome subsuming all-cause mortality. RESULTS: During the 54-month study period, 422,822 Clalit Health Services members were tested for calcidiol, of which 12,280 died of any cause (905 with acute coronary syndrome) and 3933 were diagnosed with acute coronary syndrome. Compared to those with 20-36 ng/mL, the adjusted hazard ratios among those with levels of <10, 10-20, and >36 ng/mL were 1.88 (confidence interval [CI]: 1.80-1.96), 1.25 (CI: 1.21-1.30), and 1.13 (CI: 1.04-1.22) (P < .05), respectively. LIMITATIONS: The study cohort comprised only 30% of the population, those tested for vitamin D. The small sample size of those with calcidiol >36 ng/mL prevented further analysis of this group. CONCLUSIONS: Vitamin D in the 20-36 ng/mL range was associated with the lowest risk for mortality and morbidity. The hazard ratio below and above this range increases significantly.

The impact of refeeding on blood fatty acids and amino acid profiles in elderly patients: a metabolomic analysis.

BACKGROUND: Refeeding of elderly frail patients after food deprivation is commonly associated with a high mortality rate. OBJECTIVE: To evaluate the effect of refeeding on metabolite fluctuation of blood carnitine fatty acids (15 compounds) and free amino acids (14 compounds). METHODS: Metabolite fluctuation was followed up in an exploratory, cohort, and noninterventional study in elderly and frail patients (84.5 ± 5 years) after a long period of food deprivation. Patients in the study group were refed by enteral nutrition (EN) and were followed up during 7 days for blood metabolites (n = 27). Patients in the control group (n = 26) had been fed by EN for more than 3 months. Refeeding was initiated with 10 kcal/kg/d and gradual increases of 200 kcal/d for 3 days afterwards. Blood metabolites were assayed in a sample of 25 µL. RESULTS: On food deprivation, the concentrations of all even monocarboxylic carnitine fatty acids were much higher in the study group than in the EN control group (P < .01). Upon refeeding, a remarkable decrease in all carnitine fatty acids was observed. In addition, significant daily fluctuations were observed for most metabolites in the study group of the refed patients as compared with the EN control group (P < .01). The highest fluctuations were observed following refeeding in the 7 patients who later died. CONCLUSION: A significant metabolic instability is observed on refeeding even with a slow refeeding schedule of 10 kcal/kg/d. Measurement of metabolomics parameters may be used for the evaluation of malnutrition, refeeding status, and optimization of the enteral formula.

Serum trace elements in elderly frail patients with oropharyngeal dysphagia.

Microelements have an important role in many vital enzymatic functions. Their optimal intake and serum concentration are not properly defined. For nursing home residents, this issue is further complicated by the high prevalence of oropharyngeal dysphagia. The purpose of this study was to measure microelement concentrations in 3 groups of elderly subjects that differ in their feeding methods and functional state. Forty-six frail elderly patients, in stable clinical condition, 15 on naso-gastric tube (NGT) feeding, 15 orally fed (OF), from skilled nursing departments were recruited to this study. As controls, we studied a group of 16 elderly independent ambulatory patients. A battery of 16 microelements was examined using the Inductively Coupled Plasma Atomic Emission Spectrometry (ICP-AES) and Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The OF frail elderly patients had significantly lower levels of chromium as compared to the NGT fed and the control group. Both frail elderly groups had lower levels of zinc and copper as compared to the controls. In contrast, in the nursing groups, we found higher levels of aluminum, boron, barium, bromine and nickel. Elderly, in particular frail and disabled subjects, are vulnerable to insufficiency or overload of microelements. There is a need to evaluate the actual requirements for each microelement for this population.

Mortality after nasogastric tube feeding initiation in long-term care elderly with oropharyngeal dysphagia--the contribution of refeeding syndrome.

BACKGROUND: The refeeding syndrome (RS) is an underappreciated but clinically important entity characterized by acute electrolyte abnormalities, mainly hypophosphatemia, fluid retention and dysfunction of various organs and systems, which can result in significant morbidity and occasionally death. OBJECTIVE: To examine the incidence of death cases and death causes following nasogastric tube (NGT) feeding initiation in frail elderly with particular reference to RS. METHODS: Forty patients with feeding problems for at least 72 h before restarting of alimentation by NGT were included. Excluded were those in any critical clinical situation. Clinical parameters and nutritional assessment were recorded before and after refeeding. Blood samples were taken before, daily for the first 3 days and 1 week after refeeding initiation. RESULTS: During the 1st week of refeeding, 9 patients (22.5%) died and within 1 month 10 more, summing to 47.5%. Most deaths were due to infectious causes [15 out of 19, (79%)]; some were due to no obvious reason [4 out of 19, (21%)]. Significant electrolyte changes were observed in the 2-3 days following refeeding. Significant were the decreases in phosphorus and elevations in potassium and lymphocytes (day 7). We found no correlations between the severity of decreases in levels of phosphorus and mortality. CONCLUSIONS: Mortality after NGT feeding initiation was high, mainly due to infectious complications. However, in a considerable number of patients hypophosphatemia was noted, suggesting that RS could be a contributory factor of mortality. Since this is a treatable condition, more attention should be paid to detecting and coping with this problem.

Homocysteine effect on protein degradation rates.

OBJECTIVES: To show the effect of homocysteine (Hcy) on the degradation rates of proteins. DESIGN AND METHODS: Degradation rates of short-lived proteins in neutrophils were measured in in vivo human model of elevated plasma Hcy and lower vitamin status and in animal model of Hcy added in vitro to rat neutrophils. RESULTS: In the human study, we found significant coefficients of correlation between plasma total homocysteine (tHcy) and the degradation rates of 21 protein fractions. In the animal model, Hcy significantly increased degradation rates of 57 protein fractions. CONCLUSIONS: The increase in protein degradation rates, induced by Hcy, may provide a clue to our understanding of the mechanism of Hcy detrimental effects. Hcy may amplify the specific effect of cellular solutes on protein conformation, thereby monitor protein degradation rates to control enzyme activity. Consequently, the cell may lose its ability to maintain an efficient control of some crucial metabolic pathways, possibly leading to atherogenesis.

Hyperhomocysteinemia and vitamin score: correlations with silent brain ischemic lesions and brain atrophy.

Elevated fasting plasma total homocysteine concentration (tHcy) and lower vitamin status are associated with atherosclerotic states. Silent brain ischemic lesions and brain atrophy, prevailing in the elderly, are affected by tHcy and vitamin status. The study was performed on 56 outpatients who had undergone brain computed tomography (CT) before the onset of the study. According to brain CT evaluation, three groups were set: minor brain ischemia, brain atrophy and control. Brain CT, tHcy, plasma pyridoxal phosphate (PLP), vitamin B(12), folic acid and cognitive and functional capacities were measured or evaluated in all of the subjects. Plasma vitamin score for three vitamins was calculated. In subjects with minor brain ischemic lesions (n = 21), tHcy was higher by 5.6 microM, whereas vitamin score and cognitive function were lower than in controls (n = 24). In subjects with brain atrophy (n = 11), plasma PLP and cognitive function were lower. Particular attention should be paid to tHcy monitoring, vitamin status assessment and brain impairment evaluation.