Daily Oral Supplementation Research Articles

Treatment of iron deficiency and iron deficiency anaemia in menstruating women

Iron deficiency and anaemia affect premenopausal women's quality of life. Daily oral iron supplements are standard treatment, causing gastrointestinal side effects, which could be overcome by an alternate-day dosing regimen. In this review, we compare dosing strengths and frequencies in trials: Twice-daily doses of 160 mg of elemental iron increases the ferritin- but not the haemoglobin level significantly and is poorly tolerated compared to 60-80 mg elemental iron taken daily or every other day, in mild to moderate anemia, although evidence for severe anaemia is limited.

Krill oil supplementation improves transepidermal water loss, hydration and elasticity of the skin in healthy adults: Results from two randomized, double-blind, placebo-controlled, dose-finding pilot studies.

Dietary marine omega-3 fatty acids and phospholipids have individually shown favorable effects on skin barrier function. Krill oil offers a combination of omega-3 in phospholipid form which might enhance the efficacy in supporting skin health. The aim was to investigate the impact of two different doses of krill oil on skin transepidermal water loss (TEWL) in healthy adults. Secondary outcomes were skin hydration, elasticity and the omega-3 index. Two randomized, double-blind, placebo-controlled, pilot studies were conducted in healthy adults with a baseline TEWL of >10 and ≤24.9 g/m2/h. In study 1, 51 participants consumed 1 g of krill oil or placebo daily. In study 2, 50 participants consumed 2 g of krill oil or placebo daily. The outcomes were assessed at baseline, 6 and 12 weeks. The krill oil supplemented groups significantly increased their omega-3 index versus placebo in both studies. Furthermore, the krill oil groups in both studies showed statistically significant beneficial reductions in TEWL (from 14.47 ± 3.65 to 13.83 ± 3.78 in study 1 and from 14.25 ± 3.21 to 13.02 ± 2.76 in study 2) and increases in hydration and elasticity when compared to placebo. There were significant linear relationships between changes in the omega-3 index and changes in TEWL, hydration and elasticity in both studies. Daily oral supplementation with 1 and 2 g of krill oil showed significant and dose-dependent improvements in skin TEWL, hydration, and elasticity compared to placebo that correlated with changes in the omega-3 index.

Daily oral iron supplementation during pregnancy.

Daily oral iron supplementation during pregnancy.

Efficacy of daily versus intermittent oral iron supplementation for prevention of anaemia among pregnant women: a systematic review and meta-analysis

The World Health Organization recommends daily oral supplementation of iron for prevention of maternal anaemia. However, the adverse effects due to daily supplementation leads to poor compliance among pregnant women. Also, the mucosal block theory suggests that intermittent oral iron may be more efficient than daily iron with respect to optimum absorption. Our meta-analysis reviewed the existing clinical studies for the efficacy of daily versus intermittent oral iron supplementation. In this systematic review and meta-analysis [PROSPERO ID:CRD42024498180], we searched PubMed, Google Scholar, Scopus, Science Direct and Cochrane database for studies published from 1st January 1970 to 31st December, 2023. Studies comparing daily and intermittent iron supplementation in pregnant women were included. The median intermittent iron dose was 120mg/day and daily iron dose was 60mg/day. The primary outcome was endpoint haemoglobin levels after iron supplementation. The data was analysed using the 'meta' and 'metafor' packages in RStudio using random effects model. The heterogeneity, publication bias, risk of bias and certainty of evidence were assessed using I2 statistics, funnel plots, Cochrane Risk of Bias 2 (ROB2) tool, and the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach respectively. Of 4615 search results, 26 studies (n=4365 participants) were included in this meta-analysis. There was no significant difference (p=0.18) between the endpoint mean haemoglobin levels of the daily versus intermittent oral iron groups (standardized mean difference (SMD): 0.51, 95% CI:-0.23 to 1.24, I2=97%, low certainty evidence) irrespective of baseline anaemic status. However, the endpoint ferritin levels were significantly higher in the daily supplementation group (SMD: 0.85, 95% CI: 0.15-1.54, p=0.02, I2=97%, low certainty evidence). The adjusted odds ratio for nausea, (adjusted odds ratio (OR) 3.56, 95% CI: 2.23-5.69, p<0.001, I2=9%, moderate certainty evidence), diarrhoea (adjusted OR 5.40, 95% CI: 1.90-15.33, p=0.002, I2=0%, low certainty evidence) and constipation (adjusted OR 1.95, 95% CI: 1.21-3.14, p=0.006, I2=0%, moderate certainty evidence) was significantly higher in daily oral iron supplementation group. Intermittent oral iron supplementation with a median dose of 120mg/day demonstrates comparable efficacy to daily oral iron supplementation median dose of 60mg/day in increasing haemoglobin levels among pregnant women with a significant reduction in adverse events. There was no funding for this study.

Efficacy of oral sodium chloride in reducing the incidence of hyponatremia in children with epilepsy receiving oxcarbazepine monotherapy: A randomized controlled trial (SCHO Trial)

IntroductionHyponatremia is a well-documented adverse effect of oxcarbazepine treatment, but no clinical trial has yet been conducted to explore any intervention for reducing the incidence of hyponatremia. Materials and MethodsThis open-label trial evaluated the efficacy of add-on daily oral sodium chloride supplementation of 1–2 g/day for 12 weeks in reducing the incidence of hyponatremia in children receiving oxcarbazepine monotherapy aged 1–18 years. Apart from comparing the incidence of symptomatic and severe hyponatremia, serum and urine sodium levels, serum and urine osmolality, changes in behavior and cognition, and the number of participants with recurrence of seizures and requiring additional antiseizure medication (ASM) were also compared. ResultsA total of 120 children (60 in each group) were enrolled. The serum sodium level at 12 weeks in the intervention group was higher than that of the control group (136.5 ± 2.6 vs 135.4 ± 2.5 mEq/L, p = 0.01). The number of patients with hyponatremia was significantly lower in the intervention group (4/60vs14/60, p = 0.01). However, the incidence of symptomatic and severe hyponatremia (0/60vs1/60, p = 0.67 for both), changes in social quotient and child behavior checklist total score (0.6 ± 0.8 vs 0.7 ± 0.5, p = 0.41 and 0.9 ± 1.2 vs 1.1 ± 0.9, p = 0.30 respectively), the number of patients with breakthrough seizures (9/60vs10/60, p = 0.89), and the number of patients requiring additional ASMs (8/60vs10/60, p = 0.79) were comparable in both groups. ConclusionsDaily oral sodium chloride supplementation is safe and efficacious in reducing the incidence of hyponatremia in children with epilepsy receiving oxcarbazepine monotherapy. However, sodium chloride supplementation does not significantly reduce more clinically meaningful outcome measures like symptomatic and severe hyponatremia.Trial registry No. CTRI/2021/12/038388.

Systemic Inflammation in Oncologic Patients Undergoing Systemic Treatment and Receiving Whey Protein-Based Nutritional Support.

There is increasing evidence about the role of inflammation in sarcopenia and tumor progression; thus, its modulation would represent a valuable strategy for improving clinical outcomes in patients with cancer. Several studies have reported that whey protein has significant anti-inflammatory and antioxidant characteristics in humans. We aimed to evaluate the effects of whey protein-based oral nutritional support on circulating cytokines in patients with solid tumors undergoing systemic treatment. Forty-six patients with solid tumors of different origin and undergoing systemic treatment were evaluated. Nutritional support with two daily whey protein-based oral supplements was administered. Circulating levels of IL-6, IL-8, IL-10, MCP-1 and IP-10 were determined. Nutritional evaluation included anthropometric, instrumental and biochemical parameters. Over 63% of the evaluated patients underwent surgery, 56.5% required chemotherapy and almost 50% received combined treatment. Patients with resected primary tumor presented with lower baseline IL-6 (p < 0.05) and IP-10 (p < 0.001); after three months of nutritional support, they presented with lower IL-8 (p < 0.05) and tended to present lower IL-6 and IP-10 (p = 0.053 and 0.067, respectively). Significant positive correlations between circulating cytokines, C-reactive protein and ferritin were observed; similarly, negative correlations with anthropometric and biochemical nutritional parameters were noticed (p < 0.05). We did not observe significant changes in circulating cytokine levels (IL-6, IL-8, IL-10, MCP-1 and IP-10) in patients with cancer undergoing systemic treatment after three months of nutritional support with whey protein-based oral supplements. According to a univariate analysis in our cohort, circulating IL-8 was associated with mortality in these patients, additionally, MCP-1 and IP-10 tended to correlate; but an age- and sex-adjusted multivariate analysis revealed that only baseline MCP-1 was significantly associated with mortality (OR 1.03 (95% CI: 1.00-1.05)). In conclusion, surgery of the primary solid tumor and combination treatment allow significant reduction in circulating cytokine levels, which remained stable while patients received nutritional support with whey protein-based oral supplements over three months. The role of MCP-1 as an independent factor for mortality in these patients should be further evaluated.

Iron deficiency in pregnant women: effect on offspring neuropsychic development

Increasing evidence indicates that adversities in utero and early childhood can have long-lasting effects on physiological and mental health not only in childhood but also in adulthood. Micronutrient deficiency, and in particular iron deficiency, is one of the most significant factors. Based on literature data, to determine the effect of iron deficiency in pregnant women on the neuropsychological development of infants, as well as to determine a cohort of pregnant women who need iron supplements. The search was conducted in MEDLINE (from PubMed), EMBASE (from OVID), Cochrane Library and ClinicalTrials.gov from 2010 to December 2023 without language restrictions. Data were extracted. Primary outcomes included iron deficiency, serum ferritin less than 15 μg/L in pregnant women, perinatal outcomes, and development of children in infancy. The data of serum ferritin in umbilical cord blood in newborns were compared with the serum ferritin of mothers. Data on iron supplementation and its effect on perinatal outcomes were assessed. Daily oral iron supplementation during pregnancy in women without IDA or ID reduces the incidence of iron deficiency anemia at the woman’s due date, reduces the incidence of iron deficiency in fullterm neonates, and reduces the incidence of morbidity in low-birth-weight infants. Iron supplementation during pregnancy and the postpartum period is a strategy for timely replenishment of ID and prevention of IDA to reduce cerebral iron deficiency in the fetus and newborn. The absence of side effects and high bioavailability, enhanced by ascorbic acid, allow us to recommend SunActive®Fe Bonoferlat as a daily supplement for pregnant and lactating women, according to WHO recommendations.

Ergothioneine promotes longevity and healthy aging in male mice

Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age. This was compatible with dramatical suppression by ERGO of the age-related increments in plasma biomarkers (BMs) such as the chemokine ligand 9, creatinine, symmetric dimethylarginine, urea, asymmetric dimethylarginine, quinolinic acid, and kynurenine. The oral intake of ERGO also rescued age-related impairments in learning and memory ability, which might be associated with suppression of the age-related decline in hippocampal neurogenesis and TDP43 protein aggregation and promotion of microglial shift to the M2 phenotype by ERGO ingestion. Ingestion of ERGO may promote longevity and healthy aging in male mice, possibly through multiple biological mechanisms.

Stable iron (58Fe) isotopic measurements in Kenyan toddlers during 3 months of iron supplementation demonstrate that half of the iron absorbed is lost.

Increased iron loss may reduce the effectiveness of iron supplementation. The objective of this study was to determine if daily oral iron supplementation increases iron loss, measured using a stable isotope of iron (58Fe). We enrolled and dewormed 24 iron-depleted Kenyan children, 24-27 months of age, whose body iron was enriched and equilibrated with 58Fe given at least 1 year earlier. Over 3 months of supplementation (6 mg iron/kg body weight [BW]/day), mean (±SD) iron absorption was 1.10 (±0.28) mg/day. During supplementation, 0.55 (±0.36) mg iron/day was lost, equal to half of the amount of absorbed iron. Supplementation did not increase faecal haem/porphyrin or biomarkers of enterocyte damage and gut or systemic inflammation. Using individual patient data, we examined iron dose, absorption and loss among all available long-term iron isotopic studies of supplementation. Expressed in terms of body weight, daily iron loss was correlated significantly with iron absorption (Pearson's r = 0.66 [95% confidence interval 0.48-0.78]) but not with iron dose (r = 0.16 [95% CI -0.10-0.40]). The results of this study indicate that iron loss is increased with daily oral iron supplementation and may blunt the efficacy of iron supplements in children. This study was registered at ClinicalTrials.gov as NCT04721964.

Beneficial effects of a new probiotic formulation on adipocytokines, appetite-regulating hormones, and metabolic parameters in obese women.

Obesity is often accompanied by low-grade chronic inflammation and metabolic syndrome. It has been established that microbiota influences many physiological processes, including the development of obesity, and dysbiosis has been observed in obese individuals. In this study, we aimed to evaluate the impact of a new probiotic formulation, containing two probiotic strains and the bioactive compound octacosanol, on body weight, metabolic parameters, and concentrations of certain adipocytokines and appetite-regulating hormones in obese women. This double blind placebo-controlled supplementary intervention study included twenty-five women in the intervention group and twenty-three in the placebo group, and it lasted 12 weeks. Daily oral supplementation included 7 × 1010 CFU of Lactiplantibacillus plantarum 299v (DSM9843), 5 × 109 CFU of Saccharomyces cerevisiae var. boulardii (DBVPG6763), and 40 mg of octacosanol or placebo. Body weight, metabolic parameters, adipocytokines, and appetite-regulating hormones were assessed before (T0) and after the intervention (T1). After the intervention, significantly lower median concentrations of CRP (p = 0.005) and IL-6 (p = 0.012) were measured in the intervention group than the baseline, while the median concentrations of ghrelin (p = 0.026) and HDL-cholesterol (p = 0.03) were significantly increased. The intervention group had lower CRP levels (p = 0.023) and higher ghrelin levels (p = 0.006) than the placebo group. Significant changes in BMI between groups were not observed. In summary, although the new probiotic formulation showed beneficial effects on IL-6, CRP, HDL, and ghrelin levels, its potential effects on regulating triglyceride, insulin, and glucose levels require further studies before the novel dietary intervention could be considered a useful adjuvant therapy and an effective strategy for the management of obesity and obesity-associated comorbidities.

PSVIII-30 Impaired Glucose-Stimulated Insulin Secretion in Intrauterine Growth-Restricted Neonatal Lambs Is Improved By Daily Supplementation of ω-3 Polyunsaturated Fatty Acid Ca2+ Salts

Abstract Maternofetal heat stress during placental development induces fetal intrauterine growth restriction (IUGR), which in turn reduces birthweight. IUGR-born livestock exhibit deficits in insulin stimulus-secretion coupling and glucose metabolism that contribute to poor growth efficiency. Thus, our objective was to determine whether daily oral supplementation of Ca2+ salts of ω-3 polyunsaturated fatty acids (ω-3 PUFA) to IUGR-born neonatal lambs improves glucose-stimulated insulin secretion and other indicators of metabolic efficiency. Maternal heat stress (40°C, 35% humidity, THI = 85) from d 40 to 95 of gestation was used to induce IUGR. Lambs were weaned at birth and hand-reared on milk replacer. Beginning at birth, lambs received daily oral boluses of 0.5 mL molasses containing 0 or 0.42 g/kg bodyweight of ω-3 PUFA (Virtus Nutrition). All lambs were fitted with femoral catheters at d 24 and a square-wave hyperglycemic clamp study was performed on d 28 to assess basal (i.e., resting) and glucose-stimulated insulin secretion (GSIS). Blood glucose concentrations did not differ among IUGR lambs (n = 8), IUGR+ω-3 lambs (n = 7), and controls (n = 12), but by study design were increased (P &amp;lt; 0.05) 205% from basal during hyperglycemic periods. Basal plasma insulin concentrations did not differ among groups, but basal glucose-to-insulin ratios were greater (P &amp;lt; 0.05) for IUGR+ω-3 lambs than for controls or IUGR lambs. During hyperglycemia, plasma insulin concentrations were 53% less (P &amp;lt; 0.05) for IUGR lambs but only 30% less (P &amp;lt; 0.05) for IUGR+ω-3 lambs compared with controls. Hyperglycemic glucose-to-insulin ratios were greater (P &amp;lt; 0.05) for IUGR lambs (3.24 ± 0.59) compared with controls (1.10 ± 0.29) and were intermediate for IUGR+ω-3 lambs (2.08 ± 0.86). Blood lactate concentrations did not differ among groups or between periods, but blood pH was was greater (P &amp;lt; 0.05) for IUGR (7.448 ± 0.006) and IUGR+ω-3 lambs (7.439 ± 0.003) compared with controls (7.422 ± 0.004). Blood partial pressure of CO2 was less (P &amp;lt; 0.05) for IUGR lambs (43.0 ± 0.3 mmHg) than for controls (46.7 ± 0.9 mmHg) and was intermediate for IUGR+ω-3 lambs (44.0 ± 0.4 mmHg). Blood HCO3 concentrations and O2-bound hemoglobin were greater (P &amp;lt; 0.05) for IUGR and IUGR+ω-3 lambs than for controls. Blood Na+ tended to be less (P = 0.07) and blood K+ was less (P &amp;lt; 0.05) for IUGR and IUGR+ω-3 lambs than for controls. Blood Ca2+ was less (P &amp;lt; 0.05) for IUGR lambs but not for IUGR+ω-3 lambs than for controls. These findings demonstrate that daily oral supplementation of Ca2+ salts of ω-3 PUFA improved deficits in insulin stimulus-secretion coupling and several other metabolic indicators observed in IUGR-born offspring. However, it did not improve all electrolyte concentrations or acid-base balance of the blood.

241 Increased Inflammatory Tone and Impaired Skeletal Muscle Growth in Intrauterine Growth-Restricted Neonatal Lambs Is Improved By Daily Supplementation of ω-3 Polyunsaturated Fatty Acid Ca2+ Salts

Abstract Low birthweight due to fetal intrauterine growth restriction (IUGR) often results from maternofetal heat stress. IUGR fetuses exhibit enhanced inflammatory tone, which persists after birth and impacts body composition, skeletal muscle growth, and metabolic function. Therefore, our objective was to determine whether daily oral supplementation of Ca2+ salts of ω-3 polyunsaturated fatty acids (ω-3 PUFA) to IUGR-born neonatal lambs improved inflammatory tone, body composition, and growth metrics. Pregnant ewes were exposed to heat stress (40°C, 35% humidity, THI = 85) from d 40 to 95 of gestation to induce IUGR. Lambs were weaned at birth and hand-reared on milk replacer. Daily oral boluses of 0.5 mL molasses containing 0 or 0.42 g/kg bodyweight of ω-3 PUFA (Virtus Nutrition) were administered. Femoral catheters were placed at d 24 and lambs were necropsied at d 30. At birth, IUGR lambs (n = 8; 3.12 ± 0.34 kg) and IUGR+ω-3 lambs (n = 7; 3.67 ± 0.32 kg) were lighter (P &amp;lt; 0.05) than controls (n = 12; 4.28 ± 0.15 kg). Plasma TNFα concentrations were greater (P &amp;lt; 0.05) at birth for IUGR (557 ± 121 pg/mL) and IUGR+ω-3 lambs (437 ± 82 pg/mL) than for controls (213 ± 78 pg/mL). Plasma TNFα concentrations remained increased (P &amp;lt; 0.05) for IUGR lambs but not for IUGR+ω-3 compared with controls at 2, 3, and 4 wk of age. Adjusted 30-d bodyweights were lighter (P &amp;lt; 0.05) for IUGR lambs (9.83 ± 0.6 kg) but not for IUGR+ω-3 lambs (11.59 ± 0.4 kg) than for controls (12.35 ± 0.2 kg). Heart and brain weights were 17% and 6% lighter (P &amp;lt; 0.05), respectively, for IUGR lambs than for controls. Brain weight deficits were resolved in IUGR+ω3 lambs, but heart weights did not differ between IUGR and IUGR+ω-3 IUGR lambs. Crown circumference/ bodyweight, abdominal circumference/ bodyweight, and cannon bone length/ bodyweight (indicators of asymmetric body composition) were 11% to 15% greater (P &amp;lt; 0.05) for IUGR lambs than for IUGR+ω-3 lambs or controls. At necropsy, IUGR lambs had lighter (P &amp;lt; 0.05) whole hindlimbs (29%) and flexor digitorum superficialis (24%), soleus (36%), biceps femoris (25%), semitendinosus (24%), gastrocnemius (29%), and longissimus dorsi (26%) muscles compared with controls. Weight deficits were partially or fully resolved in IUGR+ω-3 lambs for whole hindlimbs and for all muscles but the soleus, which did not differ from IUGR lambs. These findings demonstrate that daily oral supplementation of Ca2+ salts of ω-3 PUFA reduced the enhanced inflammatory tone observed in IUGR-born offspring, which coincided with improved skeletal muscle growth and indicators of symmetrical body composition.

IRON COMPLIANCE DURING ANTEPARTUM AND POSTPARTUM PERIOD AMONG WOMEN ATTENDING MATERNAL AND CHILD HEALTH CLINIC OF A TERTIARY HOSPITAL

Background: Daily oral iron supplementation, beginning from second trimester of pregnancy till 45 days postpartum, is recommended by national protocol to reduce risk of low birth weight, maternal anaemia and iron deficiency. The aim of the study was to assess iron compliance during antepartum and postpartum period among women attending maternal and child health clinic. Methods: A descriptive cross-sectional study was carried out among women visiting maternal and child health clinic of Tribhuvan University Teaching Hospital for first dose of infant’s pentavalent vaccine. Non-probability consecutive sampling technique was used to select 426 sample for the study. Data were collected through interview schedule using structured and semi-structured questionnaire. Data were analyzed using descriptive statistics (mean, standard deviation, etc.), and inferential statistics (simple binary logistic and multiple logistic regression). Results: Overall compliance during both pregnancy and postpartum was 61.0%. The common reason for compliance included doctors’ prescription (53.8%) followed by self-awareness (41.1%). For non-compliance, negligence or forgetfulness (16.2%) was commonest reason followed by improper information provided during pregnancy and postpartum (15.3%). Significant association was found between number of ANC visits [p=0.017,OR=0.269(0.091-0.792)], self-awareness on iron supplementation [p=&lt;0.001, OR=0.319(0.198-0.515)] and buying tablets from pharmacy rather than free supply [p=0.001, OR=0.437(0.274-0.698)]. Conclusions: Iron compliance during antenatal and postnatal period is low among women. Enhancing self-awareness on iron supplementation through education and counseling among women during antenatal and postnatal visits and regular prescription could improve iron compliance during pregnancy and postpartum period.

Four-week administration of an energy and protein dense oral nutritional supplement improves micronutrient concentrations but does not completely correct deficiencies in institutionalized malnourished older adults.

Poor food intake is common among elderly living in nursing homes, leading to micronutrient deficiency (MD). There are no recommendations for the management of MD in malnourished older adults. We conducted a single arm, open-label, multicenter interventional study in institutionalized malnourished older adults to describe the effect of a 4-week daily energy and protein dense oral nutritional supplementation (ONS, 600 kcal, 30 g protein per unit) containing 50% of the recommended daily micronutrient intake on micronutrient status. Plasma concentrations of vitamins (A, B9, B12, C, E), magnesium (Mg), selenium (Se) and zinc (Zn), and erythrocyte vitamin B9 were measured at baseline and after 4 weeks. Forty-six participants completed the study (age 87.4 ± 6.6). At baseline, the most frequent MD were Se (48%), Zn (35%), Mg (24%) and vitamin C (24%). Plasma concentrations of vitamins B9, B12, C and E, Mg, Se and Zn significantly increased and the proportion of subjects with at least one MD decreased (p = 0.006). However, after 4 weeks, 40% of subjects still had at least one MD. ONS consumption improved micronutrient status but did not correct MD in all participants. Our data suggest that the prescription of vitamin, mineral and trace element supplementation should be considered in institutionalized malnourished older adults in addition to high energy and high protein ONS.

Iron supplements in pregnant women with normal iron status: A systematic review and meta-analysis.

Effects of daily iron supplementation in iron replete pregnancy are unclear. This systematic review aimed to assess benefits and harms of oral iron supplements in pregnant women without anemia and iron deficiency. We predefined and registered a protocol in PROSPERO (CRD42020186210) and performed the review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. We searched for randomized clinical trials (RCTs) and observational studies comparing daily oral iron supplementation with no iron supplements in non-anemic iron replete pregnant women. Searches were conducted in MEDLINE (by PubMed), EMBASE (by OVID), Cochrane Library, and ClinicalTrials.gov from inception to September 2022 without language restrictions. Two authors independently screened records, extracted data, and assessed risk of bias using the revised Cochrane risk of bias tool (RoB2). One author read full-texts, assessed certainty of evidence by GRADE and conducted meta-analyses using a random-effects model. Primary outcomes included iron deficiency anemia, iron deficiency, hemoglobin >130 g/L, elevated iron status, small for gestational age newborns, low birthweight newborns, preterm birth, and congenital anomalies. Eight RCTs (2822 women) but no observational studies were eligible for inclusion. Daily oral iron supplementation in pregnancy probably reduces iron deficiency anemia at term (risk ratio [RR]: 0.51, 95% confidence interval [CI]: 0.38-0.70; 4 RCTs, 1670 women; I2 = 13%; moderate-certainty evidence) and the incidence of low birthweight babies (RR: 0.30, 95% CI: 0.13-0.68; 2 RCTs, 361 infants; I2 = 0%; moderate-certainty evidence). In addition, it may reduce iron deficiency at term (RR: 0.74, 95% CI: 0.60-0.92; 4 RCTs, 1663 women; I2 = 58%; low-certainty evidence) and the incidence of small for gestational age babies (RR: 0.39, 95% CI: 0.17-0.86; 1 RCT, 213 infants; I2 not estimable; low-certainty evidence). Daily iron supplementation in iron replete non-anemic pregnant women probably reduces the risk of maternal iron deficiency anemia at term and low birthweight.

Effect of exogenous l-carnitine on aortic stiffness in dyslipidemic adolescents: Design of a quadruple-blind, randomized, controlled interventional trial

BackgroundAtherosclerotic cardiovascular disease (ASCVD) risk factors including vascular remodeling leading to hypertension and dyslipidemia are prevalent among children and adolescents. Conflicting observational and Mendelian randomization data suggest endogenous carnitine may affect arterial stiffness and lipid traits. Because of this, we developed a study to evaluate the causal role for carnitine in arterial stiffness at a point when the lifecourse trajectory to hypertension can be modified. MethodsThis study is a mechanistic, double-blinded, randomized control trial (RCT) in 166 adolescents with dyslipidemia for the effect of 6 months of maximum dose 3 g daily oral l-carnitine supplementation (CS+) versus placebo (CS-) on aortic stiffness measured as carotid-femoral pulse wave velocity (CFPWV) and pulse pressure (PP); lipid concentrations (total cholesterol, HDL-C, triglycerides, and LDL-C) and serum fatty acid oxidation biomarkers by metabolomic analysis. ConclusionsThe simultaneous evaluation of endogenous carnitine genetic effects and exogenous l-carnitine supplementation may facilitate future therapies for youth with cardiometabolic derangement to arrest atherosclerotic changes.

136 The effects of cannabidiol on libido and heart rate in stallions

Changes in the Agriculture Improvement Act of 2018 increased popularity of Cannabidiol (CBD) as a supplement. Exogenous CBD, derived from Cannabis Sativa L., binds to cannabinoid receptors in the endocannabinoid system. These receptors are located throughout the body, CB1 being prominent in the central nervous system and CB2 in the immune system. Physiological effects of CBD have been well researched but the effects on libido have not. Lack of libido or sexual drive can be detrimental to stallion breeding productivity. The use of CBD as a calming supplement in animals is increasing due to marketing strategies. The study objective was to evaluate libido and heart rate (HR) in stallions given a daily oral CBD supplement for 90d. Two-year old stallions (n = 7) were assigned to either Control (CON; n = 3) or Cannabidiol (CBD; n = 4) treatment groups. CBD was administered at 0.6mg/kg of BW/d, while CON was administered an equal volume of olive oil, as a placebo of similar nature. Treatments were top-dressed over morning feed. Horses were weighed every Monday with dosages recalculated accordingly. Data collections occurred 2x/wk during semen collections with an artificial vagina. Behaviors were previously defined, calmly called out and logged as they occurred. Observations included time spent licking a tease mare, time to erection, time to first mount, and time to ejaculation. A Polar® heart rate monitoring system linked to the KER® ClockItapp was usedto measure HR. Variations of HR included resting HR, teasing HR, mounting HR, step-off HR, and walk-off HR. Data was analyzed using a repeated measures ANOVA within R Statistical Program®(R Core Team, 2022). Results were considered significant at P ≤ 0.05. Throughout the duration all stallions exhibited normal sexual behavior, regardless of treatment. A treatment affect was not seen for licking time between CBD and CON (11.92s ± 3.76 and 0.32s ± 0.20 respectively). There was no difference between CBD and CON for time to erection (27.64s ± 6.84 and 22.9s ± 4.76 respectively). Time to first mount CBD stallions averaged 330.6s ± 23.04, CON stallions averaged 359.5s ± 25.51, with no effect of treatment. Time to ejaculation in CBD stallions was 356s ± 23.78 and 374s ± 24.84 in CON stallions. There were no differences in behaviors over time. There was a time x day effect for walk-off HR(P = 0.04), though this was significant in both groups. No other differences in HR occurred. Long-term use of CBD for young stallions was seen to not affect libido. However, supplementation may lower HR over time. The immediate and lasting response to CBD use in mature stallions and older aggressive stallions is needed to understand the effects of using these products.

135 Effects of oral supplementation of cannabidiol on stallion spermatogenesis

Cannabidiol (CBD) is gaining popularity in the equine industry since the declassification of hemp in the 2018 farm bill. Cannabidiol, a chemical derivative collected from the plant Cannabis Sativa L., does not have the psychoactive effects of THC, and has a longer half-life. The endocannabinoid system, discovered in the 1990s, is made up of 2 main receptors: cannabinoid receptor subtype 1 (CRN1) and cannabinoid receptor subtype 2 (CRN2). Cannabinoid receptor subtype 1 has been identified in stallion reproductive tract organs including the testes, vas deferens, and prostate gland. Anandamide (AEA), and 2-arachidonoyl glycerol (2-AG), are 2 main endocannabinoids naturally secreted within the body and may have effects on reproductive processes. Although it takes high amounts of the ligand, it is thought that cannabidiol may influence the CB1 receptor. This study was conducted to determine the effects of daily oral supplementation of CBD over 90 consecutive days on seminal parameters in young stallions. Eight, 2-year-old stallions were blocked by weight and assigned to either control (CON; n = 3) or treatment (CBD; n = 4). The treatment group was administered CBD oil (0.6 mg/kg BW), while the control group was given olive oil (0.6 mg/kg BW). All horses were weighed weekly to recalculate dosage rates. Blood samples were drawn weekly via jugular vein puncture for CBD and testosterone level analysisthrough TVMDL lab systems. Stallions were acclimated and trained to collect using artificial vagina for 3 weeks leading up to first sample collection. Semen samples were collected twice weekly and immediately evaluated using a computer assisted semen analysis machine to quantify motility, concentration, and velocity rates. Data was evaluated using Statistical Program (R Core Team, 2022) as an ANOVA with repeated measures to determine effects of treatment on static velocity, rapid velocity, and testosterone levels. Results were considered significant at P < 0.05 and were considered a trend at P ≤ 0.15. Rapid velocity and static velocity were consistent in cell numbers; however, over time static velocity did show a slight numerical increase in static cells in the CBD treatment group (P ≤ 0.0874);(CBD = 270.7+-36.79, CON = 315.0 +-44.35). Average weekly testosterone levels did not differ among stallions; yet tended to decrease by week (57.03 +-9.927 ng/dl and 46.95 +-5.151 ng/dl respectively);(P ≤ 0.0749). These findings indicate that cannabidiol, had no effect on stallion spermatogenesis when fed at 0.6kg/mg consecutively for 90 d. Further research should evaluate cannabidiol effects over a longer period and with different ages of stallions.

A Phase 1 Study of Oral Vitamin D3 in Boys and Young Men With X-Linked Adrenoleukodystrophy.

There are no therapies for preventing cerebral demyelination in X-linked adrenoleukodystrophy (ALD). Higher plasma vitamin D levels have been linked to lower risk of inflammatory brain lesions. We assessed the safety and pharmacokinetics of oral vitamin D dosing regimens in boys and young men with ALD. In this open-label, multicenter, phase 1 study, we recruited boys and young men with ALD without brain lesions to a 12-month study of daily oral vitamin D3 supplementation. Our primary outcome was attainment of plasma 25-hydroxyvitamin D levels in target range (40-80 ng/mL) at 6 and 12 months. Secondary outcomes included safety and glutathione levels in the brain, measured with magnetic resonance spectroscopy, and blood, measured via mass spectrometry. Participants were initially assigned to a fixed dosing regimen starting at 2,000 IU daily, regardless of weight. After a midstudy safety assessment, we modified the dosing regimen, so all subsequent participants were assigned to a weight-stratified dosing regimen starting as low as 1,000 IU daily. Between October 2016 and June 2019, we enrolled 21 participants (n = 12, fixed-dose regimen; n = 9, weight-stratified regimen) with a median age of 6.7 years (range: 1.9-22 years) and median weight of 20 kg (range: 11.7-85.5 kg). The number of participants achieving target vitamin D levels was similar in both groups at 6 months (fixed dose: 92%; weight stratified: 78%) and 12 months (fixed dose: 67%; weight stratified: 67%). Among the 12 participants in the fixed-dose regimen, half had asymptomatic elevations in either urine calcium:creatinine or plasma 25-hydroxyvitamin D; no laboratory deviations occurred with the weight-stratified regimen. Glutathione levels in the brain, but not the blood, increased significantly between baseline and 12 months. Our vitamin D dosing regimens were well tolerated and achieved target 25-hydroxyvitamin D levels in most participants. Brain glutathione levels warrant further study as a biomarker for vitamin D and ALD. This study provides Class IV evidence that fixed or weight-stratified vitamin D supplementation achieved target levels of 25-hydroxyvitamin D in boys and young men with X-ALD without brain lesions.

Amelioration of Osteoarthritis Development by Daily Oral Supplementation of Royal Jelly.

Royal jelly (RJ), an essential food for the queen honeybee, has a variety of biological activities. Although RJ exerts preventive effects on various lifestyle-related diseases, such as osteoporosis and obesity, no study evaluated the effect of RJ on the development of osteoarthritis (OA), the most common degenerative joint disease. Here, we showed that daily oral administration of raw RJ significantly prevented OA development in vivo following surgically-induced knee joint instability in mice. Furthermore, in vitro experiments using chondrocytes, revealed that raw RJ significantly reduced the expression of inflammatory cytokines and enzymes critical for the degradation of the extracellular matrix (ECM). Similar results were observed after treatment with 10-hydroxy-2-decenoic acid, the most abundant and unique fatty acid in raw RJ. Our results suggest that oral supplementation with RJ would benefit the maintenance of joint health and prophylaxis against OA, possibly by suppressing the activity of inflammatory cytokines and ECM-degrading enzymes.