Dietary Biotin Research Articles

Reduced Dementia Risk That Originated From Protective Effect of Dietary Biotin on Brain Structure: Evidence From a Large-Population Based Cohort Study

Reduced Dementia Risk That Originated From Protective Effect of Dietary Biotin on Brain Structure: Evidence From a Large-Population Based Cohort Study

Dietary Biotin Associated With Psychological Disorders: A Prospective Study Based on 210, 907 Participants in UK Biobank

Dietary Biotin Associated With Psychological Disorders: A Prospective Study Based on 210, 907 Participants in UK Biobank

Dietary Biotin Deficiency Affects Reproductive Function and Prenatal Development in Hamsters

The effects of maternal dietary biotin deficiency on hamster embryos were examined by adding different amounts of avidin (0, 10, 50, 100 or 1000 mg/kg diet) to a semipurified commercial diet during the entire period of gestation. On d 10 of gestation, reduced dietary biotin resulted in a high incidence of resorbed and dead embryos. In addition, both the crown-rump length and head length of dietary biotin-deficient embryos were lower, and their digit development was retarded. These embryos were characterized by pericardial cavity enlargement (40%) and zig-zag closure line of the neural tube (44%). Some embryos exhibited abnormalities of the craniofacial region and tail. On d 14 of gestation, embryonic growth retardation, morphological abnormalities and skeletal defects were seen in the dietary biotin-deficient group (fed 100 mg avidin/kg diet). The striking abnormalities were cleft palate, micromelia, micrognathia and rib deformities in approximately 10% of the fetuses. Histological examination of the placentae revealed some differences in the spongiotrophoblast and labyrinth layers between the control and dietary biotin-deficient groups. The teratogenic effect of dietary biotin deficiency previously observed in mice was confirmed in hamsters.

Dietary High-Dose Biotin Intake Activates Fat Oxidation and Hepatic Carnitine Palmitoyltransferase in Rat

This study investigated the effects of dietary high-dose biotin intake on fat oxidation in rats using respiratory gas analysis, and evaluated fatty-acid oxidation-related enzyme activities and gene expressions in the liver. Five-week-old male Sprague-Dawley rats were fed a control diet and three biotin-supplemented diets (additive biotin concentration: 0.05%, 0.10%, and 0.20% of diet) for 3 wk. In 2 wk, fat oxidation in the 0.20% biotin-supplemented diet group was higher than that in the 0.05% biotin-supplemented diet group; however, the energy expenditure and carbohydrate oxidation were unchanged between the dietary groups. At the end of 3 wk, body weight and epididymal white adipose tissue weight reduced in the 0.20% biotin diet group, and hepatic triglyceride levels tended to decrease. Additionally, increased plasma adiponectin concentration and hepatic mitochondrial carnitine palmitoyltransferase activity as well as decreased hepatic acetyl-CoA carboxylase 2 gene expression were observed in the 0.20% biotin-supplemented diet group compared with those in the control group. These results provide strong evidence that dietary high-dose biotin intake activated fat oxidation due to the increase in hepatic β-oxidation, which may contribute to the decrease in hepatic triglyceride concentration and white adipose tissue weight.

Biotin alleviates hepatic and intestinal inflammation and apoptosis induced by high dietary carbohydrate in juvenile turbot (Scophthalmus maximus L.)

Excessive dietary carbohydrate commonly impairs the functions of liver and intestine in carnivorous fish. In the present study, a 10-week feeding trial was carried out to explore the regulation of biotin on the hepatic and intestinal inflammation and apoptosis in turbot (Scophthalmus maximus L.) fed with high carbohydrate diets. Three isonitrogenous and isolipidic experimental diets were designed as follows: the CC diet with 18.6% of carbohydrate and 0.04 mg/kg of biotin, the HC diet with 26.9% of carbohydrate and 0.05 mg/kg of biotin, and the HCB diet with 26.9% of carbohydrate and 1.62 mg/kg of biotin. Results showed that high dietary carbohydrate (HC diet) impaired the morphology of liver and intestine, however, inclusion of dietary biotin (HCB diet) normalized their morphology. Inflammation-related gene expression of nuclear factor κB p65 (nf-κb p65), tumor necrosis factor α (tnf-α), interleukin-1β (il-1β), il-6 and il-8, and the protein expression of NF-κB p65 in the liver and intestine were significantly up-regulated in the HC group compared to those in the CC group (P < 0.05), the HCB diet decreased their expression compared to the HC group (P < 0.05). The gene expression of il-10 and transforming growth factor-β (tgf-β) in the liver and intestine were significantly decreased in the HC group compared to the CC group (P < 0.05), and inclusion of dietary biotin increased the il-10 and tgf-β expression in the liver and intestine (P < 0.05). Moreover, compared to the CC group, the HC group had a stronger degree of DNA fragmentation and more TUNEL-positive cells in the liver and intestine, and the HCB group had a slighter degree of DNA fragmentation and fewer TUNEL-positive cells compared to the HC group. Meanwhile, the gene expression of B-cell lymphoma protein-2-associated X protein (bax) and executor apoptosis-related cysteine peptidase 3 (caspase-3) were significantly up-regulated and the gene expression of B-cell lymphoma-2 (bcl-2) was significantly down-regulated both in the liver and intestine in the HC group compared with those in the CC group (P < 0.05). Inclusion of dietary biotin significantly decreased the bax and caspase-3 mRNA levels and increased bcl-2 mRNA level in the liver and intestine (P < 0.05). In conclusion, high dietary carbohydrate (26.9% vs 18.6%) induced inflammation and apoptosis in liver and intestine. Supplementation of biotin (1.62 mg/kg vs 0.05 mg/kg) in diet can alleviate the high-dietary-carbohydrate-induced hepatic and intestinal inflammation as well as inhibit apoptosis in turbot. The present study provides basic data for the application of biotin into feed, especially the high-carbohydrate feed for turbot.

Effects of biotin deficiency on short term memory: The role of glutamate, glutamic acid, dopamine and protein kinase A

Insufficient dietary biotin intake, biotinidase deficiency, drug-biotin interactions can cause biotin deficiency which may result in central nervous system dysfunctions. We hypothesized that biotin deficiency could disrupt learning and memory functions by altering glutamate, glutamine, dopamine levels and protein kinase A (PKA) activity in the hippocampus.Sixteen female and 4 male Wistar rats were mated and females were separated into 4 groups. Three pups were selected from each mother and a total of 48 pups were divided into the following experimental groups. NN group, normal diet in the prenatal and postnatal period. NB group, normal diet in the prenatal and a biotin-deficient diet in the postnatal period. BN group: biotin-deficient diet in the prenatal and a normal diet in the postnatal period, BB group: biotin-deficient diet in both the prenatal and postnatal period. Open Field, Y-Maze, Object Location, and Novel Object Recognition Tests were performed in all groups and rats were sacrificed. Glutamine, glutamate, dopamine levels and PKA activity were analyzed in the hippocampi.In the open field test, distance and velocity values of NB, BN and BB groups were decreased with respect to the NN group. Learning and memory functions of NB, BN and BB groups were found to be impaired in behavioral tests. Dopamine levels and PKA activity were also decreased in all rat pups fed with a biotin deficient diet.In conclusion, we demonstrated that biotin deficiency deteriorates short-term memory and locomotor activity. This impairment may relate to decreased dopamine levels and PKA activity in the hippocampus.

Biotin controls intestinal stem cell mitosis and host-microbiome interactions.

Diet is a key regulator of metabolism and interacts with the intestinal microbiome. Here, we study the role of the Drosophila intestinal stem cell (ISC)-specific biotin transporter Smvt in midgut homeostasis, infection-induced regeneration, and tumorigenesis. We show that Smvt-transported biotin in ISCs is necessary for ISC mitosis. Smvt deficiency impairs intestinal maintenance, which can be rescued by the human Smvt, encoded by SLC5A6. ISC-specific, Smvt-silenced flies exhibit microbial dysbiosis, whereby the growth of Providencia sneebia, an opportunistic pathogen, is favored. Dysbiosis correlates with increased Nox expression, reactive oxygen species (ROS), and enterocyte apoptosis. Flies acquire biotin from their diet and microbiota. We show that, when dietary biotin is scarce, biotin-producing commensals, e.g., E.coli, can rescue reduced ISC mitosis. Smvt and commensals also control intestinal tumor growth. Our findings suggest that direct modification of the gut microbiome by biotin can serve as an approach for the treatment of dysbiosis-promoted diseases and tumorigenesis control.

Dietary biotin supplementation increases proliferation pathways in mice testes without affecting serum follicle-stimulating hormone levels and stem cell factor expression

Supplements containing pharmacological concentrations of biotin are commercially available. The mechanisms by which biotin at pharmacological concentrations exerts its action have been the subject of multiple investigations, particularly for biotin's medicinal potential and wide use for cosmetic purposes. Several studies have reported that biotin supplementation increases cell proliferation; however, the mechanisms involved in this effect have not yet been characterized. In a previous study, we found that a biotin-supplemented diet increased spermatogonia proliferation. The present study was focused on investigating the molecular mechanisms involved in biotin-induced testis cell proliferation. Male BALB/cAnNHsd mice were fed a control or a biotin-supplemented diet (1.76 or 97.7 mg biotin/kg diet) for eight weeks. Compared with the control group, the biotin-supplemented mice presented augmented protein abundance of the c-kit-receptor and pERK1/2Tyr204 and pAKTSer473, the active forms of ERK/AKT proliferation signaling pathways. No changes were observed in the testis expression of the stem cell factor and in the serum levels of the follicle-stimulating hormone. Analysis of mRNA abundance found an increase in cyclins Ccnd3, Ccne1, Ccna2; Kinases Cdk4, Cdk2; and E2F; and Sp1 & Sp3 transcription factors. Decreased expression of cyclin-dependent kinase inhibitor 1a (p21) was observed but not of Cdkn2a inhibitor (p16). The results of the present study identifies, for the first time, the mechanisms associated with biotin supplementation-induced cell proliferation, which raises concerns about the effects of biotin on male reproductive health because of its capacity to cause hyperplasia, especially because this vitamin is available in large amounts without regulation.

The negative impacts of dietary biotin deficiency on antioxidant status, apoptosis and tight junction protein transcription of immune organs in grass carp (Ctenopharyngodon idella)

Low-molecular-weight vitamin biotin is an essential nutrient substance for all animal normal growth. Previous exploration has documented that dietary biotin deficiency led to fish growth retardation and a decrease in immunity, whereas its detrimental impacts on fish other physiological status were still not revealed yet. Herein, further exploration was performed to excavate the latent influence of dietary biotin deficiency on antioxidant status, apoptosis and tight junction protein of immune organs (the skin, spleen and head kidney). In this research, grass carp (Ctenopharyngodon idella) (117.11 ± 0.48 g) as a model were fed six graded levels of biotin diets (0.012, 0.110, 0.214, 0.311, 0.427 and 0.518 mg/kg diet) in triplicate for 70 days, followed by a challenge with A. hydrophila for 6 days. Our data from above three immune organs manifested that biotin deficiency (0.012 mg/kg diet): (1) markedly increased oxidative damage degree as evidenced by the obtained highest value in all oxidative damage indicators and exhibited the lowest significant value in almost all antioxidant enzymes activities and corresponding gene expressions, where this action may be in part correlated with the modulation of Nrf2 signaling (P < 0.05); (2) signally aggravated cell apoptosis by altering the expression profiles of mitochondria and death receptor pathways involved genes (such as caspase-3,8 and FasL), where this mechanism may be partly connected with p38MAPK signaling (P < 0.05); (3) dramatically damaged tight junctions by regulating the expression profiles of a series of complexes (such as occludin and claudins), where the reason may be in part correlated with myosin light chain kinase (MLCK) signaling (P < 0.05). Differently, the transcriptional levels of MnSOD, GPx4, JNK and ZO-2 (only in spleen) were not regulated by dietary biotin in above three immune organs (P > 0.05). Furthermore, a broken line analysis showed that dietary biotin requirement levels for on-growing grass carp is 0.245–0.354 mg/kg diet for parameters (ROS content, caspase3 and claudin-3c expression levels).

45-Year-Old Woman With Fever and Malaise

45-Year-Old Woman With Fever and Malaise

Efficient induction of proximity-dependent labelling by biotin feeding in BMAL1-BioID knock-in mice.

Proximity-dependent biotin identification (BioID) is a useful method to identify unknown protein-protein interactions. Few reports have described genetically engineered knock-in mouse models for in vivo BioID. Thus, little is known about the proper method for biotin administration and which tissues are applicable. Here, we established a BioID knock-in mouse model of Brain and Muscle ARNT-Like 1 (BMAL1) and the BirA biotin ligase with R118G mutation (BirA*). The BMAL1-BioID mouse model was used to investigate the effect of biotin diet feeding on protein biotinylation in several tissues. The BMAL1-BirA* fusion protein-retained proper intracellular localization of BMAL1 and binding to CLOCK protein in HEK293T cells. A biotin labelling assay in mouse embryonic fibroblasts revealed the protein biotinylation activity of BMAL1-BirA* expressed in knock-in mouse cells depending on biotin supplementation. Lastly, feeding a 0.5% biotin diet for 7 days induced protein biotinylation in the brain, heart, testis and liver of BMAL1-BioID mice without adverse effects on spermatogenesis. In the kidney, the biotin diet increased biotinylated protein levels in BMAL1-BioID and control mice, suggesting the existence of endogenous biotinylation activity. These results provide valuable information to optimize the in vivo BioID procedure.

Interactive effects of dietary biotin and carbohydrate on growth performance and glucose metabolism in juvenile turbot Scophthalmus maximus L.

A 10-week feeding trial was conducted to explore the effects of dietary biotin and carbohydrate and their interactions on the growth performance and glucose metabolism in juvenile turbot (Scophthalmus maximus L.). Six isonitrogenous and isolipidic diets from a 2 × 3 factorial design was formulated with two levels of carbohydrate (16% and 25%) and three levels of biotin (0 mg/kg, 0.25 mg/kg and 1.5 mg/kg) respectively. The results showed that juvenile turbots fed with 16% of dietary carbohydrate and 1.5 mg/kg of biotin had the highest specific growth rate (SGR) and higher activities of intestinal amylase and stomach pepsin. Dietary biotin lowered the postprandial plasma glucose at 9 h and 24 h, regardless of dietary carbohydrate levels. However, postprandial plasma glucose at 24 h in groups with 25% of dietary carbohydrate was consistently higher than those in groups with 16% of dietary carbohydrate, regardless of dietary biotin levels. In conclusion, dietary biotin significantly decreased plasma glucose by increasing insulin level in plasma, activating PI3K (phosphoinositide 3-kinase)/AKT (protein kinase b) signaling pathway, promoting glucose transportation, glycolysis, pentose phosphate pathway and glycogen synthesis but inhibiting gluconeogenic pathway. Compared with the increased plasma glucose and growth inhibition in juvenile turbot caused by excessive dietary carbohydrate level (25%), however, the hypoglycemic effect of biotin is limited.

Biotin Controls Intestinal Stem Cell Mitosis and Host-Microbiome Interactions

Detrimental alterations in intestinal microbiota, known as dysbiosis, predispose to inflammation that can lead to tumorigenesis. We show that dysbiosis can also result from impaired intestinal stem cell (ISC) metabolism. We found that the Drosophila intestinal ISC-specific biotin transporter Smvt is necessary for Jak/Stat pathway-mediated ISC mitosis. ISC-specific Smvt silencing impairs intestinal maintenance, which can be partially-rescued by the human Smvt, encoded by SLC5A6. Smvt-deficient flies exhibit microbial dysbiosis, whereby the growth of Providencia sneebia, an opportunistic pathogen, is favored. Dysbiosis correlates with increased Nox expression, ROS and enterocyte apoptosis. Flies acquire biotin from their diet and microbiota. We found that when dietary biotin is scarce, biotin-producing commensals, e.g. E. coli, can rescue reduced ISC mitosis. Smvt and commensals also control intestinal tumor growth. Our findings suggest that direct modification of the gut microbiome by biotin can serve as an approach for the treatment of dysbiosis-promoted diseases and tumorigenesis control.

Response to a glucose tolerance test in early-lactation Holstein cows receiving a supplementation of biotin, folic acid, and vitamin B12

The aim of the study was to evaluate glucose and insulin metabolism of cows receiving a supplementation of biotin (B8), folic acid (B9), and vitamin B12 (B12) during the transition period. According to a 2 × 2 factorial arrangement, 32 cows were randomly assigned to 9 incomplete blocks according to their previous 305-d milk yield. Within each block, cows were randomly assigned to 1 of the following levels of biotin from -27 to 28 d relative to the parturition: (1) no biotin supplement (B8-) or (2) 20 mg/d of dietary biotin (B8+). Within each level of biotin, the cows received either (1) 2-mL weekly intramuscular injections of saline 0.9% NaCl (B9B12-) or (2) 2.6 g/d of dietary folic acid and 2-mL weekly intramuscular injections of 10 mg of vitamin B12 (B9B12+). An intravenous glucose tolerance test was performed at 25 d in milk. Baseline plasma glucagon, glucose, and nonesterified fatty acid concentrations did not differ among treatments. For B9B12+ cows, baseline plasma insulin concentration and maximal glucose concentration after glucose administration were greater when also combined with biotin compared with no biotin combination, whereas there was no effect in B9B12- cows. There was no treatment effect on time to reach half-maximal glucose and insulin concentrations, glucose positive incremental area under the curve, and glucose and insulin clearance rates. Regarding insulin results, maximal plasma concentration and positive incremental area under the curve were respectively 51 and 74% greater for cows receiving the B8 supplement than for cows who did not. Moreover, plasma nonesterified fatty acid concentration nadir tended to be reached later for B8 cows. Insulin peak was reached earlier for cows in the group B9B12+ than cows in B9B12-, regardless of B8 supplementation. Under the current conditions, our results suggested that cows receiving a B8 supplement had a reduced insulin sensitivity in early lactation. Insulin response was faster for B9B12+ cows, but this was not translated into further improvements following the glucose administration challenge.

Effects of Different Levels of Dietary Biotin on The Performance, Apparent Digestibility And Carcass Characteristics of Broilers

Effects of Different Levels of Dietary Biotin on The Performance, Apparent Digestibility And Carcass Characteristics of Broilers

Metabolomic Analysis of Liver from Dietary Biotin Deficient Mice.

Biotin is a water-soluble B-complex vitamin that functions as a cofactor of five carboxylases. Because biotin-dependent carboxylases catalyze indispensable cellular metabolic functions, biotin deficiency is considered to be involved in various pathological conditions. Moreover, biotin supplementation shows pharmacological effects in vivo. However, the precise mechanisms by which biotin deficiency induces pathological conditions remain unclear. Although abnormal metabolites are used as indicators for biotin deficiency, few comprehensive analyses of total metabolites have been reported. In this study, we analyzed the metabolomic profiles of liver extracts prepared from biotin-sufficient (BS) and -deficient (BD) mice. Thirteen of 126 metabolites showed significantly different concentrations between liver extracts from BD and BS mice. The concentrations of 5 essential amino acids, Met, Val, Thr, Ile, and Leu, and 2 conditionally essential amino acids, Cys and Tyr were significantly lower in BD mice than in BS mice. Among these, the concentrations of sulfur-containing amino acids, Cys and Met, were more than 1.5-fold lower in BD mice. The concentrations of Met metabolites, such as S-adenosylmethionine and S-adenosylhomocysteine were not significantly different between the two groups. The concentrations of glutathione and its reaction intermediates γ-Glu-Cys tendency to be lower in BD mice. The present study revealed that biotin deficiency induces an abnormal amino acids composition, especially among sulfur-containing amino acids and provide important information on the effect of biotin as a pharmacological agent.

Dietary biotin deficiency decreased growth performance and impaired the immune function of the head kidney, spleen and skin in on-growing grass carp (Ctenopharyngodon idella)

The aim of this study was to investigate the effects of dietary biotin deficiency on the growth performance and immune function of the head kidney, spleen and skin in on-growing grass carp (Ctenopharyngodon idella). A total of 540 on-growing grass carp (117.11 ± 0.48 g) were fed six diets containing increasing levels of biotin (0.012, 0.110, 0.214, 0.311, 0.427 and 0.518 mg/kg diet) for 70 days. Subsequently, a challenge experiment was performed by infecting them with Aeromonas hydrophila for six days. Our results showed that compared with the appropriate biotin level, (1) biotin deficiency (0.012 mg/kg diet) reduced the activities of lysozyme (LZ) and acid phosphatase (ACP), decreased the contents of complement 3 (C3), C4 and immunoglobulin M (IgM), as well as reduced the mRNA levels of antimicrobial peptides in the head kidney, spleen and skin of on-growing grass carp; (2) biotin deficiency reduced the mRNA levels of anti-microbial substances: liver-expressed antimicrobial peptide (LEAP) -2A, LEAP-2B, hepcidin, β-defensin-1 and mucin 2 in the head kidney, spleen and skin of on-growing grass carp; (3) biotin deficiency increased the mRNA levels of pro-inflammatory cytokines interleukin 1β (IL-1β), IL-6, IL-8, IL-12p40, IL-15, IL-17D, tumour necrosis factor α (TNF-α) and interferon γ2 (IFN-γ2) partially in association with nuclear factor-kappa B (NF-κB) signalling and reduced anti-inflammatory IL-4/13A, IL-10, IL-11 and transforming growth factor β1 (TGF-β1) mRNA levels partially in association with target of rapamycin (TOR) signalling in the head kidney, spleen and skin of on-growing grass carp. Interestingly, biotin deficiency had no effect on the expression of IL-12p35, IL-4/13B, TGF-β2, 4E-BP1 (skin only) or IKKα in the head kidney, spleen and skin of on-growing grass carp. In conclusion, the results indicated that biotin deficiency impaired the immune function of the head kidney, spleen and skin in fish. Finally, based on the percent weight gain (PWG), the ability to prevent skin haemorrhages and lesions, the LZ activity in the head kidney and the C4 content in the spleen, the optimal dietary biotin levels for on-growing grass carp (117–534 g) were estimated as 0.210, 0.230, 0.245 and 0.238 mg/kg diet, respectively.

Dietary Biotin Supplementation Impairs Testis Morphology and Sperm Quality.

Supplements containing pharmacological concentrations of biotin are commercially available over the counter. Classical toxicity studies have considered biotin administration as harmless; however, recent investigations have shown that biotin supplementation modifies tissue morphology without changes in toxicity markers, raising concerns about the consequences of morphological changes on tissues' functions and the safety of pharmacological concentrations of the vitamin. Testes are very sensitive to toxicants, and testicular histology is a reliable method to study its function. In this work, we investigated the effects of dietary biotin supplementation on testis morphology and spermatogenesis function using an experimental model, in which we have not observed unfavorable effects on other tissue functions or toxicity markers. Male BALB/cAnNHsd mice were fed a control or a biotin-supplemented diet (1.76 or 97.7 mg biotin/kg diet) for 8 weeks. Compared to the control group, the biotin-supplemented mice presented remarkable testis morphology changes, including increased spermatogonia layers; the cellular mechanism involved is related to increased proliferation. Sperm count and serum testosterone levels were not affected, but spermatozoa motility and morphology were significantly impaired in the biotin-supplemented mice. These results caution against the use of supplements with high concentrations of biotin and indicate that biotin's pharmacological effects on morphology need to be considered in toxicological studies.

Effect of maternal biotin, folic acid, and vitamin B12 supplementation before parturition on colostral and Holstein calf plasma concentrations in those vitamins

The newborn calf relies on placental and colostral transfers of B vitamins to cover its requirements. This study was conducted to evaluate biotin, folate and vitamin B12 concentrations in colostrum of cows receiving those vitamin supplements and in plasma of their calves fed with their colostrum. According to a 2 × 2 factorial arrangement, non-lactating pregnant cows (n = 34) were assigned to 2 levels of biotin supplement (0 or 20 mg/day of dietary biotin) and 2 levels of folic acid and vitamin B12 supplements (0 or 2.6 g/day of dietary folic acid and 10 mg of intramuscular injections of vitamin B12). Treatments were initiated 26 (SD: 8) days before calving until the parturition. Colostrum sample from the first milking was harvested. Offspring (n = 23) were fed 2.4 (SE: 0.3) kg of their dam colostrum within 3 (SD: 2) h of life (P > 0.24); calves born as twin, stillborn or not receiving their dam colostrum were removed. Calves were blood sampled and weighed 25 (SD: 4) h after birth. Supplementary biotin, folic acid, and vitamin B12 successfully increased their respective prepartum dam plasma and colostrum vitamin concentrations (P < 0.001). Colostral biotin, folate, and vitamin B12 concentrations were respectively increased from 26.8 (95% confidence interval (CI): 20.4–35.1) to 253.7 (95% CI: 193.8–332.3), 673 to 1094 (SE: 52), and 28.6 to 57.9 (SE: 3.3) ng/mL by their respective vitamin supplementation. Colostral IgG concentration did not differ among treatments (P > 0.14) and averaged 49.8 (SD: 23.5) g/L. Calves born to dams receiving folic acid and vitamin B12 supplements were heavier (50 vs. 44, SE: 1 kg; P = 0.003); biotin supplement did not affect calf weight (P = 0.66). Plasma biotin concentrations of calves were increased from 1.1 (95% CI: 0.9–1.4) to 7.5 (95% CI: 6.1–9.2) ng/mL by the maternal biotin supplementation (P < 0.001). Maternal folate and vitamin B12 supplementation during the prepartum period increased calf plasma concentration of folates from 15.9 (SE: 1.9) to 30.8 (SE: 1.8) ng/mL and tended to augment plasma vitamin B12 concentration of offspring, from 0.76 (95% CI: 0.51–1.12) to 1.25 (95% CI: 0.87–1.80) ng/mL (P < 0.07). No treatment effect was noted on calf plasma concentration of IgG (P > 0.54). Results suggest that biotin, folic acid and vitamin B12 supplementation given to the dam before calving increased supply of those vitamins for newborn calves who rely on external supply of the B vitamins to fulfill their requirements before the development of their functional rumen.

Awareness of vitamin B7: A growing problem in clinical practice

Biotin (vitamin B7, hexahydro-2-oxo-1H-thieno[3,4-d]imidazole-4-pentanoic acid) is not synthesized by mammals: dietary sources include plant based foods, yeast, liver, kidneys, heart, pancreas, egg yolk, poultry, and cow’s milk. Synthesis via the gut bacteria may also play a role. Recommended daily allowances are based on normal intake; EU RDA is 50 μg/day, the US adequate intake (AI) for adults is 30 μg/day.Biotin is required for the function of four carboxylases: pyruvate carboxylase, propionyl CoA carboxylase, multiple CoA carboxylase, and acetylCoA carboxylase I and II. Holocarboxylase synthase is required to attach biotin to their active sites. Biotin also modulates the expression of up to 2000 genes, and has effects on immune function, largely through biotinylation of histones and other proteins.Biotinidase, the enzyme which splits biotin from biotinyl lysine (biocytin), and from peptides containing biocytin, recycles biotin from endogenous turnover and facilitates absorption from exogenous sources, together with the sodium-dependent multivitamin transporter.Nutritional deficiency of biotin is rare and most cases relate to inborn errors of biotin metabolism and transport, long-term use of parenteral nutrition, chronic anticonvulsant therapy, or avidin binding of dietary biotin due to excessive ingestion of egg whites.Excessive ingestion of biotin from supplements is increasingly common. Biotin has no direct toxicity, but high circulating levels can interfere with many commercially available immunoassays which use the interaction between biotin and streptavidin. This can result in a spurious but plausible biochemical picture of disease supported by two or more independent immunoassay based tests.The laboratory detection of functional biotin deficiency relies upon detection of multiple carboxylase deficiency, identified and followed by measurement of urinary 3-hydroxyisovaleric acid (3HIVA, ideally using isotope dilution GC-MS, or isotope dilution-LC-MSMS (ID-LC-MSMS)) or plasma 3-hydroxyisovaleryl carnitine (3HIVc, measured using ID-LC-MSMS). These methods are reviewed, together with methods for assessing biotinidase activity.This chapter also describes methods for the direct measurement of biotin in foods, blood, serum/plasma, and urine. These relied for many years on microbiological assays. These were followed by binding assays using avidin with radioactive biotin or enzyme linked biotin as tracers, with or without chromatographic separation to distinguish between biotin, metabolites of biotin, and biotinylated peptides. Latterly, the introduction of specific assays using ID-LC-MSMS should allow traceable and harmonized assay of plasma/serum biotin. These could be particularly helpful to detect excessive ingestion of biotin supplements.We conclude that there is a need for laboratory methods with adequate sensitivity and specificity to reliably diagnose biotin deficiency and monitor biotin levels in patients receiving supplements. There are a limited number of reliable markers of biotin status and no single marker can reliably distinguish moderately deficient biotin from sufficient and supplemented. Measurement of 3HIVA and 3HIVc, the functional markers of biotin status, is currently the recommended approach.