Transdermal Delivery of Niacin Through Polysaccharide Films Ameliorates Cutaneous Flushing in Experimental Wistar Rats.

BACKGROUND: Niacin, an established therapeutic for dyslipidemia, is hindered by its propensity to induce significant cutaneous flushing when administered orally in its unmodified state, thereby constraining its clinical utility. OBJECTIVE: This study aimed to fabricate, characterize, and assess the in-vitro and in-vivo effectiveness of niacin-loaded polymeric films (NLPFs) comprised of carboxymethyl tamarind seed polysaccharide. The primary objective was to mitigate the flushing-related side effects associated with oral niacin administration. METHODS: NLPFs were synthesized using the solvent casting method and subsequently subjected to characterization, including assessments of tensile strength, moisture uptake, thickness, and folding endurance. Surface characteristics were analyzed using a surface profiler and scanning electron microscopy (SEM). Potential interactions between niacin and the polysaccharide core were investigated through X-ray diffraction experiments (XRD) and Fourier transform infrared spectroscopy (FTIR). The viscoelastic properties of the films were explored using a Rheometer. In-vitro assessments included drug release studies, swelling behavior assays, and antioxidant assays. In-vivo efficacy was evaluated through skin permeation assays, skin irritation assays, and histopathological analyses. RESULTS: NLPFs exhibited a smooth texture with favorable tensile strength and moisture absorption capabilities. Niacin demonstrated interaction with the polysaccharide core, rendering the films amorphous. The films displayed slow and sustained drug release, exceptional antioxidant properties, optimal swelling behavior, and viscoelastic characteristics. Furthermore, the films exhibited biocompatibility and non-toxicity towards skin cells. CONCLUSION: NLPFs emerged as promising carrier systems for the therapeutic transdermal delivery of niacin, effectively mitigating its flushing-associated adverse effects.

Relationship between dietary niacin intake and erectile dysfunction: a population-based study.

Existing research on the precise link between dietary niacin intake and erectile dysfunction (ED) is scarce. Thus, this study aimed to investigate the potential association between dietary niacin intake and the risk of ED. Multivariate logistic regression and restricted cubic splines (RCSs) were used to examine the relationship between dietary niacin intake and ED. Subgroup interaction analysis was performed to assess the impact of different subgroups on the study outcomes. In addition, 1:1 propensity score matching (PSM) was employed to adjust for potential confounding factors, ensuring the reliability of the results. The analyzed data were collected from the 2001-2004 National Health and Nutrition Examination Survey (NHANES) in the USA. The study encompassed 3184 adults, among whom 863 participants were identified as having ED. Following adjustments for potential confounders, the findings revealed that higher niacin intake, specifically in the highest tertile, was associated with a decreased risk of ED compared to that in the lowest tertile, showing an odds ratio (OR) of 0.56 (95% confidence interval [CI]: 0.37-0.85). Analysis of dose-response curves illustrated a negative correlation between dietary niacin intake and the risk of ED. Subgroup and interaction analyses fortified the consistency of these results. Furthermore, PSM corroborated the validity of the findings. This study suggests an inverse association between dietary niacin intake and the risk of ED. However, establishing a cause-and-effect relationship remains elusive, and defining the safe threshold of niacin intake to prevent ED requires further investigation.

Effect of Egg-White Protein Alone or Combined With Niacin on Nutritional Status, and Phosphorus Control in Maintenance Hemodialysis Patients: A Randomized Controlled Trial.

OBJECTIVE: Niacin is reported to decrease phosphorus concentration in maintenance hemodialysis (MHD) patients. Egg white is one of the main substitutable proteins in MHD patients due to its low phosphorus content. Therefore, we aimed to evaluate the effects of combined egg white and niacin supplementation on dialysis patients' serum phosphorus and nutritional biomarkers. DESIGN AND METHODS: In this randomized controlled clinical trial, 98 patients on MHD were randomly allocated to four groups for 8 weeks: 24 g egg white (n = 25), 600 g niacin daily (n = 24), egg white combined with niacin (n = 24), and control (n = 24). Calcium, phosphorus, fibroblast growth factor-23, and other nutritional markers were assessed. RESULTS: There was a significant difference among the groups only in phosphorus at the end of the trial, which was significantly lower in the niacin group (4.38 + 0.812 mg/dL) than in both the egg white (5.07 + 0.49 mg/dL) and egg white with niacin supplementation (5.41 + 0.662 mg/dL) groups. In this regard, albumin increased in egg white and egg white with niacin supplementation, while albumin did not change significantly in the niacin group. Urea reduction ratio and Kt/V rose only in the egg-white group, while aspartate aminotransferase increased only in the niacin and control groups. CONCLUSION: Niacin decreases serum phosphorus concentration more than egg-white protein or a combined intervention. Egg white protein supplementation has beneficial effects on some nutritional statuses other than phosphorus control without the side effects of niacin.

Dose-response association between dietary folate and niacin intakes with diabetes among Chinese adults: a cross-sectional study.

BACKGROUND: The aim of this study was to examine the relationship between dietary intake of folate and niacin and diabetes risk in Chinese adults. METHODS: This is a cross-sectional study. Demographic and anthropometric data along with information on dietary intake of vitamins were collected, and eligible participants were recruited to complete the questionnaire. A binary logistic regression analysis was conducted to examine the association between dietary intake of vitamins and diabetes risk, with adjustment for potential confounders. Non-linear dose-response relationships between dietary intake of folate and niacin and diabetes risk were also evaluated using adjusted restricted cubic splines. RESULTS: Of the 3106 eligible participants, 15.9% had diabetes. Median folate was significantly higher in diabetic patients than in controls (32.030 vs. 27.600 gµ), while median niacin was significantly lower (7.000 vs. 7.900 mg). After controlling for potential confounders, binary logistic regression analysis showed that each unit increase in folate intake was associated with a 1.002-fold increase in the risk of developing diabetes (odds ratio (OR) = 1.002; 95% confidence interval (CI) 1.000-1.004; P = 0.022), while each unit increase in niacin intake was associated with a 3.5% reduction in diabetes risk (OR = 0.965; 95% CI 0.944-0.986; P = 0.001). The plots of restricted cubic splines presented an atypical inverted U-shaped association between dietary intake of folate and diabetes risk. CONCLUSIONS: Diabetic patients had a low intake of vitamins, especially the B vitamins. Dietary intake of folate and niacin tended to be independently associated with the risk of diabetes. Nevertheless, this study is observational and a large-scale randomized controlled trial is yet to be conducted, which will add to the evidence of the study results.

Association between B-vitamins intake and frailty among patients with chronic obstructive pulmonary disease.

PURPOSE: Gain insight into the impact of B vitamins, including vitamin B1, vitamin B2, niacin, vitamin B6, total folate, and vitamin B12 on the risk of frailty in patients with chronic obstructive pulmonary disease (COPD). METHODS: This study was an American population-based cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES). A total of 1201 COPD patients were included in the analysis. Of these, the intake of B vitamins was determined by the two 24-h recall interviews. We followed the method constructed by Hakeem et al. to calculate the frailty index (FI), which is used as a reliable tool to assess the debilitating status of patients with COPD. Missing data were imputed by the MissForest method based on random forests. Multivariate logistic regression model and inverse probability weighted based on propensity scores were used to correct for confoundings. RESULTS: Logistic regression models showed that vitamin B6 intake was negatively correlated with frailty risk in COPD patients, while other B vitamins including B1, B2, niacin (vitamin B3), total folic acid and vitamin B12 were not. After adjusting for covariates, the association between vitamin B6 and frailty risk (adjusted OR = 0.80, 95%CI = 0.66-0.95, P = 0.013) remained significant. At the same time, sensitivity analysis proves the robustness of the results. CONCLUSION: COPD patients with lower vitamin B6 intake have a higher risk of frailty. However, intake of vitamin B1, B2, niacin, total folic acid, and vitamin B12 was not associated with frailty risk in COPD patients.

B Vitamins Supplementation Can Improve Cognitive Functions and May Relate to the Enhancement of Transketolase Activity in A Rat Model of Cognitive Impairment Associated with High-fat Diets.

OBJECTIVE: To determine whether B vitamin treatment was sufficient to reduce cognitive impairment associated with high-fat diets in rats and to modulate transketolase (TK) expression and activity. METHODS: To test this, we separated 50 rats into five groups that were either fed a standard chow diet (controls) or a high-fat diet (experimental groups H0, H1, H2, and H3). H0 group animals received no additional dietary supplementation, while H1 group animals were administered 100 mg/kg body weight (BW) thiamine, 100 mg/kg BW riboflavin, and 250 mg/kg BW niacin each day, and group H2 animals received daily doses of 100 mg/kg BW pyridoxine, 100 mg/kg BW cobalamin, and 5 mg/kg BW folate. Animals in the H3 group received the B vitamin regimens administered to both H1 and H2 each day. RESULTS: Over time, group H0 exhibited greater increases in BW and fat mass relative to other groups. When spatial and memory capabilities in these animals were evaluated via conditioned taste aversion (CTA) and Morris Water Maze (MWM), we found B vitamin treatment was associated with significant improvements relative to untreated H0 controls. Similarly, B vitamin supplementation was associated with elevated TK expression in erythrocytes and hypothalamus of treated animals relative to those in H0 (P<0.05). CONCLUSION: Together, these findings suggest B vitamin can modulate hypothalamic TK activity to reduce the severity of cognitive deficits in a rat model of obesity. As such, B vitamin supplementation may be a beneficial method for reducing cognitive dysfunction in clinical settings associated with high-fat diets.

NAMPT reduction-induced NAD+ insufficiency contributes to the compromised oocyte quality from obese mice.

Maternal obesity is associated with multiple adverse reproductive outcomes, whereas the underlying molecular mechanisms are still not fully understood. Here, we found the reduced nicotinamide phosphoribosyl transferase (NAMPT) expression and lowered nicotinamide adenine dinucleotide (NAD+ ) content in oocytes from obese mice. Next, by performing morpholino knockdown assay and pharmacological inhibition, we revealed that NAMPT deficiency not only severely disrupts maturational progression and meiotic apparatus, but also induces the metabolic dysfunction in oocytes. Furthermore, overexpression analysis demonstrated that NAMPT insufficiency induced NAD+ loss contributes to the compromised developmental potential of oocytes and early embryos from obese mice. Importantly, in vitro supplement and in vivo administration of nicotinic acid (NA) was able to ameliorate the obesity-associated meiotic defects and oxidative stress in oocytes. Our results indicate a role of NAMPT in modulating oocyte meiosis and metabolism, and uncover the beneficial effects of NA treatment on oocyte quality from obese mice.

A peculiarly characterised case of isoniazid-induced pellagra- 2 Ds and a C: a case report.

Niacin or tryptophan deficiency causes pellagra. Isoniazid interferes with the absorption of niacin and individuals on Isoniazid (INH) are at risk of pellagra. Isoniazid preventive therapy (IPT) is the administration of isoniazid to immunosuppressed individuals to prevent active tuberculosis (TB). IPT, in sub-Saharan Africa, the region worst hit by HIV and with a high TB prevalence, is recommended. A 40-year-old, HIV+ Zambian woman on Antiretroviral therapy for five years and IPT for three months presented with a four-day history of constipation, generalised body weakness and irrelevant talk. She complained of a generalised rash, sloughing off, and darkening of the skin on the face, neck, forearms, and dorsum of both feet. A physical examination revealed features of pellagra, and rapid response to oral niacin reaffirmed the diagnosis of pellagra. Unlike typical cases of pellagra presenting with the classic 3 Ds of Diarrhoea, Dementia and Dermatitis, our patient presented with constipation instead of diarrhoea. A consideration of Pellagra in HIV+ patients on IPT whose diet is mostly maize-based will be beneficial, even if the classic 3 Ds of diarrhoea, dementia, and dermatitis are not wholly present. A timely diagnosis and prompt treatment of pellagra can be lifesaving.

Higher Dietary Inflammation in Patients with Schizophrenia: A Case-Control Study in Korea.

Inflammation is a risk factor for the onset and progression of schizophrenia, and dietary factors are related to chronic inflammation. We investigated whether the dietary inflammatory index (DII) is associated with schizophrenia in the Korean population. Of the 256 subjects who responded to the questionnaire, 184 subjects (117 controls; 67 individuals with schizophrenia) were included in this case-control study. A semi-quantitative food frequency questionnaire was used to evaluate the dietary intakes of the study participants. The energy-adjusted DII (E-DII) was used to assess the inflammatory potential of the participants' diets. Dietary intakes of vitamin C, niacin, and folate were significantly reduced in the patients with schizophrenia. The patients with schizophrenia had higher E-DII scores than the controls (p = 0.011). E-DII was positively associated with schizophrenia (odds ratio = 1.254, p = 0.010). The additional analysis confirmed that E-DII was significantly associated with schizophrenia, especially in the third tertile group of E-DII scores (odds ratio = 2.731, p = 0.016). Our findings suggest that patients with schizophrenia have more pro-inflammatory diets.

Dietary niacin affects intestinal morphology and functions via modulating cell proliferation in weaned piglets.

Niacin deficiency leads to inflammation of mucous membranes and diarrhoea. There are few reports on the effects of niacin on the intestinal health of weaned piglets. The present study was conducted to analyse the effects of niacin in weaned piglets along with its underlying mechanism. A total of 48 25-day-old weaned piglets (24 females and 24 males) were randomly allotted into four groups, each treatment were supplemented with 22.5, 30, 45, and 75 mg kg-1 niacin for a period of 14 days, with 12 piglets per diet and 1 piglet per pen. Six piglets (3 males and 3 females) were randomly selected from each treatment group and euthanised for intestinal tissue sampling on days 7 and 14 after the weaning day (day 0), respectively. Dietary niacin did not affect the growth performance of weaned piglets but quadratically affected (P < 0.05) the diarrhoea rate from days 7 to 14. The duodenal villus height and width and crypt depth in the 30 mg kg-1 niacin group were greater than those in the 45 mg kg-1 niacin group on day 7, and the jejunal crypt depth, ileal crypt depth, villus height and villus width decreased (linear, P < 0.05) with the increase in dietary niacin. However, the dietary supplementation with niacin increased (linear, P < 0.001) the jejunal villus height, crypt depth and villus width on day 14. Dietary niacin increased (linear, P < 0.05) the alkaline phosphatase activity in the jejunal mucosa of weaned piglets on day 7 but decreased (linear, P < 0.05) its activity on day 14. The number of Ki67 positive cells per crypt was decreased (linear, P < 0.05) with the dietary niacin on day 7 but increased (linear, P < 0.05) with dietary niacin contents on day 14. Moreover, dietary niacin altered (P < 0.05) SLC5A1, SLC15A1, SLC6A19, TJP-1, occludin and claudin-1 mRNA expression in the small intestine. These results indicate that dietary niacin has different effects on intestinal morphology and functions in the first and second weeks postweaning and that the dietary supplementation with niacin may, by modulating intestinal cell proliferation, affect the intestinal health.

Chronic niacin administration ameliorates ovulation, histological changes in the ovary and adiponectin concentrations in a rat model of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common ovarian diseases among women of reproductive age. The reproductive and metabolic traits of PCOS are underpinned by adipocyte dysfunction, especially diminished adiponectin secretion. Based on evidence that niacin stimulates adiponectin secretion, this study evaluated the effects of niacin on adiponectin concentrations and reproductive traits in a rat model of PCOS. PCOS was induced by single injection of 4mg kg-1 oestradiol valerate (i.m.), and PCOS groups were administered orally with saline or niacin (10 or 25mg kg-1) daily for 30 days after PCOS induction. The control group received 0.2mL sesame oil (i.m.) only. At the end of the experimental period, serum samples and ovaries were collected for adiponectin, histological and molecular analyses. Niacin reduced the bodyweight gain and increased ovary weights in PCOS rats. Niacin also increased the number of normal antral follicles and corpora lutea while reducing the number of cystic follicles and the thickness of theca interna. Moreover, niacin significantly increased serum adiponectin concentration and the gene expression of adiponectin and its type 1 receptor. In conclusion, this study indicates that niacin reduces cystic follicles and improves ovulation in PCOS rats. Adiponectin signalling may have contributed, in part, to the beneficial effects.

The efficacy of niacin supplementation in type 2 diabetes patients: Study protocol of a randomized controlled trial.

BACKGROUND: Dyslipidemia is a main risk factor of cardiovascular disease in the diabetic patients. Niacin was found acutely to decrease the plasma concentration of free fatty acids by inhibiting their mobilization from adipose tissue. This present study is a double blinded, randomized, and prospective trial to determine the effect of niacin during dyslipidemia in type 2 diabetic patients. METHODS: This randomized controlled, double-blinded, single center trial is carried out according to the principles of Declaration of Helsinki. This present study was approved in institutional review committee of the Second Affiliated Hospital of Dalian Medical University. All the patients received the informed consent. Diabetic patients were randomized (1:1) to receive 3-month treatment with extended-release niacin or matching placebo. The major outcome of our present study was the change in the level of HbA1c from the baseline to week 12. Secondary outcome measures contained the levels of fasting blood glucose, the concentrations of serum transaminase, the other laboratory variables, and self-reported adverse events. The P < .05 was regarded as statistically significant. RESULTS: We assumed that adding the niacin to the medication in patients with type 2 diabetes would reduce dyslipidemia and achieve target lipid levels. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5925).

The comparative impact among different intensive statins and combination therapies with niacin/ezetimibe on carotid intima-media thickness: a systematic review, traditional meta-analysis, and network meta-analysis of randomized controlled trials.

PURPOSE: To compare the impact of different statins therapies on the reduction of carotid intima-media thickness (CIMT) may reflect their cardiovascular benefits which is useful in clinical decision. METHODS: PubMed, EMBASE, Cochrane Library, and Web of Science were searched, and 3539 articles published from 1992 to 2020 were retrieved. CIMT in randomized controlled trials for statins therapies were included for traditional and network meta-analyses analyzed by Stata 16. The quality of included studies was assessed by the Cochrane Collaboration's tool. RESULTS: Thirty-three randomized controlled trials (n=8762) were eligible for network meta-analysis, of which 18 randomized controlled trials (n=5252) were included for comparison between statins and no statins and 11 randomized controlled trials (n=1338) were included for comparison between high-intensity statins or combination with niacin/ezetimibe and moderate/low-intensity statins in 2 traditional meta-analyses. In the traditional meta-analyses, the statins groups significantly reduce CIMT compared to no statins (standard mean difference=-0.207, 95% confidence interval: -0.291 to -0.123, p<0.001), while high-intensity statins or combination with niacin/ezetimibe performed significant CIMT reduction compared to moderate/low-intensity statins (standard mean difference=-0.287, 95% confidence interval: -0.460 to -0.114, p=0.001). In the network meta-analysis, a relative rank for the ability to reduce CIMT was given as follows: combination therapy with niacin (mean rank: 1.7), high-intensity statins, combination therapy with ezetimibe, and moderate/low-intensity statins. CONCLUSION: Statins combined with niacin performed a greater CIMT reduction compared to high-intensity statins alone and combination therapies with ezetimibe. The advantage of niacin-combined statins therapies to improve cardiovascular endpoint needs further validation through randomized controlled trials. CLINICAL TRIAL REGISTRATION: PROSPERO, CRD42020175972.

Bioequivalence of levamlodipine besylate tablets in healthy Chinese subjects: a single-dose and two-period crossover randomized study.

BACKGROUND: Levamlodipine, a calcium channel blocker, has been show act as a cardiovascular drug. To compare the pharmacokinetic parameters between levamlodipine (test formulation) at a single dose of 5 mg and amlodipine (reference formulation) at a single dose of 10 mg, the bioequivalence study was carried out. METHODS: A single-dose randomized, open-label, two-period crossover study was designed in healthy Chinese subjects. 48 subjects were divided into fasted and fed groups equally. The subjects randomly received the test or reference formulations at the rate of 1:1. Following a 21-day washout period, the alternative formulations were received. The blood samples were collected at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 24, 36, 48, 72, 96, 120, 144, 168 h later. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied to determine the plasma concentrations of levamlodipine. Adverse events were recorded. RESULTS: The 90% confidence intervals (CIs) of the ratio of geometric means (GMRs) of Cmax, AUC0-t, and AUC0-∞ under both fasted and fed conditions were within the prespecified bioequivalence limits between 80 ~ 125%. Under fasted conditions, 24 subjects were enrolled and completed the study. The mean Cmax was (2.70 ± 0.49) ng/mL, AUC0-t was (141.32 ± 36.24) ng × h/mL and AUC0-∞ was (157.14 ± 45.65) ng × h/mL after a single dose of 5 mg levamlodipine. The mean Cmax was (2.83 ± 0.52) ng/mL, AUC0-t was (153.62 ± 33.96) ng × h/mL and AUC0-∞ was (173.05 ± 41.78) ng × h/mL after a single dose of 10 mg amlodipine. Under fed conditions, 24 subjects were enrolled and completed the study. The mean Cmax was (2.73 ± 0.55) ng/mL, AUC0-t was (166.93 ± 49.96) ng × h/mL and AUC0-∞ was (190.99 ± 70.89) ng × h/mL after a single dose of 5 mg levamlodipine. The mean Cmax was (2.87 ± 0.81) ng/mL AUC0-t was (165.46 ± 43.58) ng × h/mL and AUC0-∞ was (189.51 ± 64.70) ng × h/mL after a single dose of 10 mg amlodipine. Serious adverse event was not observed. CONCLUSION: The trial confirmed that levamlodipine at a single dose of 5 mg and amlodipine at a single dose of 10 mg were bioequivalent under both fasted condition and fed condition. TRIAL REGISTRATION: Cinicaltrials, NCT04411875 . Registered 3 June 2020 - Retrospectively registered.

Nutritional Optic Neuropathies: State of the Art and Emerging Evidences.

Nutritional optic neuropathy is a cause of bilateral, symmetrical, and progressive visual impairment with loss of central visual acuity and contrast sensitivity, dyschromatopsia, and a central or centrocecal scotoma. The clinical features are not pathognomonic, since hereditary and toxic forms share similar signs and symptoms. It is becoming increasingly common due to the widespread of bariatric surgery and strict vegetarian or vegan diets, so even the scientific interest has recently increased. In particular, recent studies have focused on possible pathogenetic mechanisms, and on novel diagnostic and therapeutic strategies in order to prevent the onset, make a prompt diagnosis and an accurate nutritional supplementation, and to avoid irreversible optic nerve atrophy. Nowadays, there is clear evidence of the role of cobalamin, folic acid, thiamine, and copper, whereas further studies are needed to define the role of niacin, riboflavin, and pyridoxine. This review aims to summarize the etiology, diagnosis, and treatment of nutritional optic neuropathy, and it is addressed not only to ophthalmologists, but to all physicians who could come in contact with a patient with a possible nutritional optic neuropathy, being a fundamental multidisciplinary approach.

Effectiveness of niacin supplementation for patients with type 2 diabetes: A meta-analysis of randomized controlled trials.

BACKGROUND: Lipid profiles and glycemic control play a critical role in subsequent atherosclerotic cardiovascular disease for patients with type 2 diabetes mellitus (T2DM). This study aimed to evaluate the effectiveness of niacin supplementation on lipid profiles and glycemic control for patients with T2DM. METHODS: The PubMed, Embase, and the Cochrane Library databases were searched to identify randomized controlled trials (RCTs) that investigated the effects of niacin supplementation for patients with T2DM throughout December 2019. The weighted mean differences (WMDs) with 95% confidence intervals (CIs) were applied to calculate the pooled effect estimates using a random-effects model. RESULTS: Eight RCTs comprised a total of 2110 patients with T2DM who were selected for final quantitative analysis. The patients' niacin supplementation was associated with lower levels of total cholesterol (WMD, -0.28; 95% CI, -0.44 to -0.12; P = .001), triglyceride (WMD, -0.37; 95% CI, -0.52 to -0.21; P < .001), and low-density lipoprotein (WMD, -0.42; 95% CI, -0.50 to -0.34; P < .001). Moreover, the level of high-density lipoprotein was significantly increased when niacin supplementation (WMD, 0.33; 95% CI, 0.21 to 0.44; P < .001) was provided. However, niacin supplementation produced no significant effects on plasma glucose (WMD, 0.18; 95% CI, -0.14 to 0.50; P = .275) and hemoglobin A1c (HbA1c) levels (WMD, 0.39; 95% CI, -0.15 to 0.94; P = .158). CONCLUSIONS: This study found that niacin supplementation could improve lipid profiles without affecting the glycemic levels for patients with T2DM. Additional large-scale RCTs should be conducted to evaluate the long-term effectiveness of niacin supplementation.

Micronutrient supplementation of lactating Guatemalan women acutely increases infants' intake of riboflavin, thiamin, pyridoxal, and cobalamin, but not niacin, in a randomized crossover trial.

BACKGROUND: Maternal supplementation during lactation could increase milk B-vitamin concentrations, but little is known about the kinetics of milk vitamin responses. OBJECTIVES: We compared acute effects of maternal lipid-based nutrient supplement (LNS) consumption (n = 22 nutrients, 175%-212% of the RDA intake for the nutrients examined), as a single dose or at spaced intervals during 8 h, on milk concentrations and infant intake from milk of B-vitamins. METHODS: This randomized crossover trial in Quetzaltenango, Guatemala included 26 mother-infant dyads 4-6 mo postpartum who were randomly assigned to receive 3 treatments in a random order: bolus 30-g dose of LNS (Bolus); 3 × 10-g doses of LNS (Divided); and no LNS (Control), with control meals. Mothers attended three 8-h visits during which infant milk consumption was measured and milk samples were collected at every feed. Infant intake was assessed as $\mathop \sum \nolimits_{i\ = \ 1}^n ( {{\rm{milk\ volum}}{{\rm{e}}_{{\rm{feed\ }}n}} \times \ {\rm{nutrient\ concentratio}}{{\rm{n}}_{{\rm{feed}}\ n}}} )$ over 8 h. RESULTS: Maternal supplementation with the Bolus or Divided dose increased least-squares mean (95% CI) milk and infant intakes of riboflavin [milk: Bolus: 154.4 (138.2, 172.5) µg · min-1 · mL-1; Control: 84.5 (75.8, 94.3) µg · min-1 · mL-1; infant: Bolus: 64.5 (56.1, 74.3) µg; Control: 34.5 (30.0, 39.6) µg], thiamin [milk: Bolus: 10.9 (10.1, 11.7) µg · min-1 · mL-1; Control: 7.7 (7.2, 8.3) µg · min-1 · mL-1; infant: Bolus: 5.1 (4.4, 6.0) µg; Control: 3.4 (2.9, 4.0) µg], and pyridoxal [milk: Bolus: 90.5 (82.8, 98.9) µg · min-1 · mL-1; Control: 60.8 (55.8, 66.3) µg · min-1 · mL-1; infant: Bolus: 39.4 (33.5, 46.4) µg; Control: 25.0 (21.4, 29.2) µg] (all P < 0.001). Only the Bolus dose increased cobalamin in milk [Bolus: 0.054 (0.047, 0.061) µg · min-1 · mL-1; Control: 0.041 (0.035, 0.048) µg · min-1 · mL-1, P = 0.039] and infant cobalamin intake [Bolus: 0.023 (0.020, 0.027) µg; Control: 0.015 (0.013, 0.018) µg, P = 0.001] compared with Control. Niacin was unaffected. CONCLUSIONS: Maternal supplementation with LNS as a Bolus or Divided dose was similarly effective at increasing milk riboflavin, thiamin, and pyridoxal and infant intakes, whereas only the Bolus dose increased cobalamin. Niacin was unaffected in 8 h. This trial was registered at clinicaltrials.gov as NCT02464111.