Vitamin deficiencies in children: Lessons from clinical and neuroimaging findings.

BACKGROUND AND AIMS: Water-soluble vitamins play an essential coenzyme role in the nervous system. Acquired vitamin deficiencies are easily treatable, however, without treatment, they can lead to irreversible complications. This study aimed to provide clinical, laboratory parameters and neuroimaging data on vitamin deficiencies in an attempt to facilitate early diagnosis and prompt supplementation. METHODS: From July 1998 to July 2023, patients at Necker-Enfants-Malades Hospital presenting with acute neurological symptoms attributed to acquired vitamin deficiency were included. Clinical data were extracted from Dr Warehouse database. Neuroimaging, biochemical and electrophysiological data were reviewed. RESULTS: Patients with vitamin B1 deficiency exhibited abnormal eye movements (n = 4/4), fluctuations in consciousness (n = 3/4), and ataxia (n = 3/4). Brain MRI showed alterations of fourth ventricle region (n = 4/4), periaqueductal region (n = 4/4), tectum (n = 3/4), and median thalami (n = 3/4). Patients with vitamin B2 deficiency presented with early onset hypotonia (n = 3/4), hyperlactatemia (n = 4/4), and hyperammonemia (n = 4/4). Plasma acylcarnitines revealed a multiple acyl-coA dehydrogenase deficiency-like profile (n = 4/4). In vitamin B12 deficiency, young children presented with developmental delay (n = 7/7) and older children with proprioceptive ataxia (n = 3/3). Brain MRI revealed atrophy (n = 7/7) and spinal MRI hyperintensity in posterior cervical columns (n = 3/3). Metabolic findings showed elevated methylmalonic acid (n = 6/7) and hyperhomocysteinemia (n = 6/7). Patients with vitamin C deficiency exhibited gait disturbances and muscle weakness (n = 2/2). CONCLUSIONS: Acquired vitamin deficiencies may display reversible clinical symptoms mimicking inherited metabolic disorders. Some situations raise suspicion for diagnosis: concordant clinical presentation, suggestive neuroimaging findings, and/or biochemical evidence. Any acute neurological condition should be treated without waiting for definitive biochemical confirmation.

Vitamin Supplement Use in Patients With CKD: Worth the Pill Burden?

All vitamins play essential roles in various aspects of body function and systems. Patients with chronic kidney disease (CKD), including those receiving dialysis, may be at increased risk of developing vitamin deficiencies due to anorexia, poor dietary intake, protein energy wasting, restricted diet, dialysis loss, or inadequate sun exposure for vitamin D. However, clinical manifestations of most vitamin deficiencies are usually subtle or undetected in this population. Testing for circulating levels is not undertaken for most vitamins except folate, B12, and 25-hydroxyvitamin D because assays may not be available or may be costly to perform and do not always correlate with body stores. The last systematic review through 2016 was performed for the Kidney Disease Outcome Quality Initiative (KDOQI) 2020 Nutrition Guideline update, so this article summarizes the more recent evidence. We review the use of vitamins supplementation in the CKD population. To date there have been no randomized trials to support the benefits of any vitamin supplementation for kidney, cardiovascular, or patient-centered outcomes. The decision to supplement water-soluble vitamins should be individualized, taking account the patient's dietary intake, nutritional status, risk of vitamins deficiency/insufficiency, CKD stage, comorbid status, and dialysis loss. Nutritional vitamin D deficiency should be corrected, but the supplementation dose and formulation need to be personalized, taking into consideration the degree of 25-hydroxyvitamin D deficiency, parathyroid hormone levels, CKD stage, and local formulation. Routine supplementation of vitamins A and E is not supported due to potential toxicity. Although more trial data are required to elucidate the roles of vitamin supplementation, all patients with CKD should undergo periodic assessment of dietary intake and aim to receive various vitamins through natural food sources and a healthy eating pattern that includes vitamin-dense foods.

Fat-soluble vitamin deficiency and exocrine pancreatic insufficiency among adults with chronic pancreatitis: Is routine monitoring necessary for all patients?

Chronic pancreatitis (CP) is often associated with exocrine pancreatic insufficiency (EPI), which may increase risk for fat-soluble vitamin depletion. Although vitamin D deficiency is widespread among the general population, vitamins A, E, and K deficiencies may more uniquely present in patients with CP. Yet, it is unclear whether fat-soluble vitamin status should be routinely monitored in all patients with CP or limited to those with EPI. The purpose of this review is to describe the laboratory status of vitamins A, E, and K in adult patients with CP and their association with exocrine pancreatic function. Five primary, observational studies met the inclusion criteria for qualitative synthesis. Biochemical deficiencies in fat-soluble vitamins were observed across trials but results varied with respect to whether EPI increased risk. Challenges related to the diagnosis and treatment of EPI along with potential confounders may contribute to the heterogeneity among study results. Although more studies are needed to determine the influence of pancreatic enzyme replacement therapy on fat-soluble vitamin status as well as effective vitamin repletion strategies, clinicians should consider periodically screening for deficiencies in all patients with CP regardless of EPI to avoid associated health effects of vitamin depletion.

Nutritional peripheral neuropathies.

Nutritional peripheral neuropathies are a global problem, heavily influenced by geopolitical, cultural and socioeconomic factors. Peripheral neuropathy occurs most frequently secondary to B-vitamin deficiencies, which is suspected to increase in years to come due to the popularity of vegan and vegetarian diets and increased use of bariatric surgery.This review will focus on the common B-vitamins for which a causal link to peripheral neuropathy is more established (vitamins B1, B2, B6, B9 and B12). We will review the historical human and animal data on which much of the clinical descriptions of vitamin deficiencies are based and summarise current available tools for accurately diagnosing a nutritional deficiency. We will also review recently described genetic diseases due to pathogenic variants in genes involved in B-vitamin metabolism that have helped to inform the phenotypes and potential causality of certain B-vitamins in peripheral neuropathy (B2 and B9).Endemic outbreaks of peripheral neuropathy over the last two centuries have been linked to food shortages and nutritional deficiency. These include outbreaks in Jamaican sugar plantation workers in the nineteenth century (Strachan's syndrome), World War two prisoners of war, Cuban endemic neuropathy and also Tanzanian endemic optic neuropathy, which remains a significant public health burden today. An improved understanding of lack of which vitamins cause peripheral neuropathy and how to identify specific deficiencies may lead to prevention of significant and irreversible disability in vulnerable populations.

Fat-Soluble Vitamins Deficiency in Pediatric Cholestasis: A Scoping Review.

BACKGROUND: This review aims to identify the current indications and gaps in the management of fat-soluble vitamins in pediatric patients with cholestasis. METHODS: A comprehensive review of the literature using PubMed, Scopus, Web of Science and Embase was performed. Two authors independently identified the most relevant studies published over the past 20 years up to February 2022, including original papers, narrative reviews, observational studies, clinical trials, systematic reviews and meta-analyses. The literature was screened, and preclinical studies about pathogenetic mechanisms were also included. Keywords searched for each fat-soluble vitamin (A, D, E and K), alone or in combination, were "cholestasis", "chronic liver disease", "biliary atresia", "malnutrition" and "nutritional needs". Studies published prior to the selected time range were searched manually and, when considered relevant, included within the list of references. RESULTS: Eight hundred twenty-six articles were initially screened. From these, 48 studies were selected. A comparison of the recommended methods of supplementation for fat-soluble vitamins was then carried out. The causes of malabsorption were explained and current methods for defining deficiency and monitoring complications were summarized. CONCLUSIONS: According to the literature, children with cholestasis are at a higher risk of fat-soluble vitamin deficiency. Although there are general recommendations, the treatment for vitamin deficiency is not uniformly validated.

Osteoporosis and sarcopenia are common and insufficiently diagnosed among chronic pancreatitis patients.

PURPOSE: Chronic pancreatitis (CP) leads to diabetes and pancreatic exocrine insufficiency (PEI). PEI may lead to maldigestion and malnutrition, which may cause fat-soluble vitamin deficiency, sarcopenia and abnormal bone density. We aim to study the prevalence of osteoporosis, sarcopenia and vitamin deficiency among CP patients. METHODS: Long-term (4-5 years) follow-up was implemented on CP patients. We recorded CP duration, BMI, smoking, alcohol consumption and medication. We determined the serum values for A, D and E vitamins, albumin, creatinine, haemoglobin, calcium and magnesium. Bone density measurement was taken from the proximal femur and lumbar spine. CT/MRI scans were used to measure for psoas muscle area. RESULTS: A total of 33 patients (median age 62 [39-81] years, 61% male) were included. None of these patients had earlier diagnosis of osteopathy, and none of them had known vitamin deficiency or were sarcopenic. Nineteen patients (57%) had pancreatic exocrine insufficiency and of these seven patients (37%) had no pancreatic enzyme replacement therapy (PERT) and one (5%) had inadequate enzyme therapy. During the study, osteoporosis was diagnosed in 20% and possible sarcopenia in 48% of patients. PEI and inadequate PERT was associated with low E vitamin levels (75% vs. 0%, p = 0.012), higher risk of osteoporosis (43% vs. 5.6%, p = 0.013) and sarcopenia (80% vs. 36%, p = 0.044). CONCLUSION: This study demonstrates that chronic pancreatitis is associated with osteoporosis, sarcopenia and vitamin deficiency. If untreated, pancreatic exocrine insufficiency is associated with increased risk of these outcomes. This highlights the importance of identifying and treating PEI in CP patients.

Low vitamin K status in adults with cystic fibrosis is associated with reduced body mass index, insulin secretion, and increased pseudomonal colonization.

Patients with cystic fibrosis (CF) are at high risk of fat-soluble vitamin deficiencies, even with supplementation. The contribution of a suboptimal vitamin K status to respiratory and endocrine pathophysiology in CF has been inadequately characterized. This is a cross-sectional study in adult CF patients (≥18 years old) from the Montreal Cystic Fibrosis Cohort. Vitamin K1 (VK1) was measured with high-performance liquid chromatography, using fasted serum samples collected during an oral glucose tolerance test (OGTT: 2 h with plasma glucose and insulin every 30 min) (n = 168). Patients were categorized according to VK1 status (suboptimal defined as <0.30 nmol/L). Suboptimal VK1 levels were observed in 66% of patients. Patients with a suboptimal VK1 status have a higher risk of colonization with Pseudomonas aeruginosa (p = 0.001), have lower body mass index (BMI) (p = 0.003), and were more likely to have exocrine pancreatic insufficiency (p = 0.002). Using an established threshold for VK1, we did show significantly reduced OGTT-derived measures of insulin secretion in patients with a VK1 status below 0.30 nmol/L (first- and second-phase area under the curve (AUC)INS/GLU (p = 0.002 and p = 0.006), AUCINS (p = 0.012) and AUCINS/GLU (p = 0.004)). Subclinical vitamin K deficiency is more common than other fat-soluble vitamin deficiencies in patients with CF. We demonstrate an association between a suboptimal VK1 status and measures of insulin secretion. We highlight the potential associations of mild vitamin K deficiency with pseudomonal colonization and lower BMI, although these need to be validated in prospective studies.

Prevalence, Pathogenesis and Management of Anemia in Inflammatory Bowel Disease: An IG-IBD Multicenter, Prospective, and Observational Study.

BACKGROUND: Anemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD), with a 6% to 74% prevalence and a negative impact on patient survival and quality of life, although the prevalence is apparently declining due to improved disease treatment. We aimed to investigate the prevalence, pathogenesis, and clinical correlates of anemia in Italian patients with IBD. METHODS: A multicenter, prospective, observational study, involving 28 Italian gastroenterology centers, was conducted to investigate the epidemiology and consequences of IBD-associated anemia. Clinical and laboratory data of anemic patients were obtained at study enrolment. RESULTS: Anemia was diagnosed in 737 of 5416 adult IBD outpatients (prevalence 13.6%); females were more commonly affected than males (odds ratio, 1.5; 95% confidence interval [CI], 1.2-1.7) and had more severe anemia. In the majority of cases, anemia was due to iron deficiency (62.5% of cases; 95% CI, 58.3%-66.6%), either isolated or in association with inflammation and/or vitamin deficiencies; anemia of inflammation accounted for only 8.3% of cases. More severe anemia was associated with increasing fatigue and worse quality of life. Only 68.9% of anemic patients with iron deficiency (95% CI, 63.4%-73.8%) and 34.6% of those with vitamin deficiencies (95% CI, 26.2%-44.2%) were properly treated with supplementation therapy. CONCLUSIONS: In Italy, the prevalence of IBD-associated anemia is lower than previously reported. Anemia of IBD is most commonly due to iron deficiency and contributes to fatigue and poor quality of life, but remains untreated in a large proportion of patients with iron and/or vitamin deficiencies. This study is registered at clinicaltrials.gov as NCT02872376.

The prevalence of inflammatory bowel disease­associated anemia is 13.6%. The prevalence is higher among females younger than 50. Anemia is usually due to iron deficiency and adversely affects fatigue and quality of life. Many patients with iron or vitamin deficiency (31% and 65%, respectively) remain untreated.

[Neurological Symptoms Associated With Vitamin Deficiency and Excess: Past and Present Findings].

Vitamin deficiencies and excesses are known to cause various types of brain or peripheral nerve injuries. Improved nutritional status and dietary patterns have led to reduced prevalence, and at least some of these conditions are rare in recent times. However, delayed diagnosis (For example, in patients with Wernicke's encephalopathy) may worsen patient prognosis even in current times. Recent studies have reported an association between cognitive function and some vitamins. In this article, we summarize past and present research focused on neurological symptoms that occur secondary to vitamin deficiencies and excesses.

Critical vitamin deficiencies in autism spectrum disorder: Reversible and irreversible outcomes.

Vitamin deficiencies are an emerging concern in the management of children with autism spectrum disorder (ASD). Particular attention is required for recognizing the variable signs caused by unbalanced food intakes. We herein report two patients with multiple vitamin deficiencies who needed critical care showing different prognoses. Patient 1 with 'Shoshin' beriberi presenting with cardiac arrest had thiamine deficiency developed severe neurological sequelae despite rapid vitamin supplementation. Patient 2, who had leg pain and a limping gait, showed a rapid recovery with intravenous infusion and tube feeding after being diagnosed with scurvy. A literature search revealed several children with ASD with critically ill thiamine deficiency, but few reports documented a life-threatening condition in the form of cardiac arrest at the onset. Considering the high observation rate of food selectivity in children with ASD, early intervention is required to prevent the exacerbation of vitamin deficiencies to severe neurological disabilities.

Fat-Soluble Vitamin Deficiencies and Disruption of the Immune System in Pancreatic Cancer: A Vicious Cycle.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is currently an increasing contributor to cancer-related mortality. Despite advances in cancer treatment, PDAC survival rates have remained roughly unchanged over the years. Specifically, late diagnosis and insensitivity to currently available therapeutic regimens have been identified as the main causes for its poor survival. Pancreatic exocrine insufficiency (PEI) is a typical complication associated with PDAC diagnosis and pancreatic surgery. Pancreatic exocrine insufficiency, a major contributor to maldigestion in PDAC, is often not treated because it remains undetected because of lack of overt signs and symptoms. In this review, we will focus on the major consequences of PEI, including the inadequacy of lipase excretion, which results in deficiency of fat-soluble vitamins. Because PDAC is known for its immune-high jacking mechanisms, we describe key features in which deficiencies of fat-soluble vitamins may contribute to the aggressive biological behavior and immune evasion in PDAC. Because PEI has been shown to worsen survival rates in patients with PDAC, detecting PEI and the related fat-soluble vitamin deficits at the time of PDAC diagnosis is critical. Moreover, timely supplementation of pancreatic enzymes and fat-soluble vitamins may improve outcomes for PDAC patients.

Role of Vitamins in Neurodegenerative Diseases: A Review.

BACKGROUND: Vitamins are the micronutrients required for boosting the immune system and managing any future infection. Vitamins are involved in neurogenesis, a defense mechanism working in neurons, metabolic reactions, neuronal survival, and neuronal transmission. Their deficiency leads to abnormal functions in the brain like oxidative stress, mitochondrial dysfunction, accumulation of proteins (synuclein, Aß plaques), neurodegeneration, and excitotoxicity. METHODS: In this review, we have compiled various reports collected from PubMed, Scholar Google, Research gate, and Science direct. The findings were evaluated, compiled, and represented in this manuscript. CONCLUSION: The deficiency of vitamins in the body causes various neurological disorders like Alzheimer's disease, Parkinson's disease, Huntington's disease, and depression. We have discussed the role of vitamins in neurological disorders and the normal human body. Depression is linked to a deficiency of vitamin-C and vitamin B. In the case of Alzheimer's disease, there is a lack of vitamin- B1, B12, and vitamin-A, which results in Aß-plaques. Similarly, in Parkinson's disease, vitamin- D deficiency leads to a decrease in the level of dopamine, and imbalance in vitamin D leads to accumulation of synuclein. In MS, vitamin-C and vitamin-D deficiency causes demyelination of neurons. In Huntington's disease, vitamin- C deficiency decreases the antioxidant level, enhances oxidative stress, and disrupts the glucose cycle. vitamin B5 deficiency in Huntington's disease disrupts the synthesis of acetylcholine and hormones in the brain.

Vitamin deficiencies/hypervitaminosis and the skin.

Vitamins are an indispensable food source and important owing to the enzyme cofactor and catalytic roles they play in the body. Fat-soluble vitamins A, D, E, K, and B12, are stored in the body and can cause problems with their excessive accumulation. Other vitamins rarely accumulate in the body because they dissolve in water and are excreted through the kidneys. Alcoholism, strict diets, insufficient parental nutrition, and gastrointestinal absorption problems may be included in the causes of vitamin deficiencies. Although clinical findings of vitamin deficiencies display different characteristics depending on the vitamins, the signs that generally occur are cutaneous pigmentation, pigmentation on mucous membranes, palmoplantar keratoderma characterized by fissures, palmar streaking, yellow streaking on the nails, nail layering, and intranail hemorrhage.

The Role of Vitamin Deficiency in Liver Disease: To Supplement or Not Supplement?

Over the past few years, growing interest has been shown for the impact of dietary requirements and nutritional factors on chronic diseases. As a result, nutritional programs have been reinforced by public health policies. The precise role of micronutrients in chronic liver disease is currently receiving particular attention since abnormalities in vitamin levels are often detected. At present, treatment programs are focused on correcting vitamin deficiencies, which are frequently correlated to higher rates of comorbidities with poor outcomes. The literature reviewed here indicates that liver diseases are often related to vitamin disorders, due to both liver impairment and abnormal intake. More specific knowledge about the role of vitamins in liver disease is currently emerging from various results and recent evidence. The most significant benefits in this area may be observed when improved vitamin intake is combined with a pharmacological treatment that may also affect the progression of the liver disease, especially in the case of liver tumors. However, further studies are needed.

Severe vitamin deficiencies in pregnancy complicated by progressive familial intrahepatic cholestasis.

Progressive familial intrahepatic cholestasis (PFIC) is a rare disease of impaired bile acid excretion which can lead to nutritional deficiencies. Vitamin deficiencies during pregnancy can result in adverse maternal and fetal outcomes. A 20-year-old primiparous woman at 30 4/7 weeks with PFIC type 2 presented with worsening cholestasis, coagulopathy and fat-soluble vitamin deficiency. She developed visual deficits and was found to have severe vitamin A deficiency. Her coagulopathy and visual deficits improved following vitamin K and A supplementation, respectively. She delivered at 32 2/7 weeks following preterm labour. This case highlights several unique aspects in the care of pregnant women with liver disease. These patients are at risk for fat-soluble vitamin deficiencies which can result in significant coagulopathy and rarely, visual deficits due to vitamin A deficiency. Prompt treatment is necessary to prevent permanent sequelae.

[A cachectic man with a severe vitamin deficiency]. / Een cachectische man met een ernstig vitaminetekort.

A 57-year-old man, known with severe malnutrition, vitamin E deficiency and peripheral neuropathies, presented with vomiting and abdominal tenderness. There was a suspicion of ileus and small bowel obstruction. During the exploratory laparotomy a complete brown colored bowel without peristalsis was seen.

A Properly Balanced Reduction Diet and/or Supplementation Solve the Problem with the Deficiency of These Vitamins Soluble in Water in Patients with PCOS.

Polycystic ovary syndrome (PCOS) is an increasingly common problem for women in the reproductive age throughout the entire world. A reduction diet with a low glycaemic index (GI) has proved to support the treatment of PCOS. The aim of the study was to analyse the influence of the diet on the level of vitamins soluble in water. The study included 55 women, 40 of which suffered from PCOS (identified by means of the Rotterdam Criteria) and 15 healthy women of the Caucasian race. The level of vitamins before and after the dietary intervention was measured. The diet was a reduction diet with a reduced glycaemic index (GI). Biochemical analyses were made on the basis of liquid chromatography-Infinity 1260 Binary liquid chromatography (LC) Agilent Technology. The level of vitamins in the serum was analysed together with the consumption before and after the dietary intervention. A higher level of vitamin C in the plasma was observed before and after the dietary intervention in the PCOS group in comparison to the control group despite the lower intake of this vitamin in the PCOS group. The remaining vitamins were at a comparable or lower level (B1, B3, B5, B6 and B12). After the dietary intervention, only B1 and B9 were at a clearly lower level (a trend of p = 0.093 and p = 0.085). A properly balanced reduction diet with reduced GI improves the supply of vitamins in women with PCOS. An additional recommendation should be the additional supplementation of B1, niacinamide and the combination of folates with inositol. The level of vitamin C in the plasma may not be a good marker of its supply in the PCOS group.

Impact of malnutrition and vitamin deficiency in geriatric patients undergoing orthopedic surgery.

Background and purpose - There is growing evidence that hypoproteinemia is an important risk factor for adverse events after surgery. Less is known about the impact of vitamin deficiency on postoperative outcome. Therefore we evaluated the prevalence and impact of malnutrition and vitamin deficiency in geriatric patients undergoing elective orthopedic surgery.Patients and methods - In a retrospective analysis of 599 geriatric patients who had undergone elective orthopedic surgery in 2018 and 2019, hypoproteinemia, and deficiency of vitamin D, vitamin B12, and folate were assessed. Reoperation rates, readmission rates, complication rates, and transfusion rates were compared between malnourished patients and patients with normal parameters. Multivariable logistic regression models were used to assess the relationship between malnutrition and postoperative adverse events, controlling for confounding factors such as age, sex, diabetes mellitus, and frailty.Results - Patients with malnutrition showed a higher rate of reoperation (13% vs. 5.5%; p = 0.01) and exhibited more wound-healing disorders (7.4% vs. 1.3%, p = 0.001) as well as Clavien-Dindo IV° complications (7.4% vs. 2.4%; p = 0.03). Deficiency of vitamin D led to a higher rate of falls (8.4% vs. 2.9%, p = 0.006). Deficiency of vitamin B12 and folate did not affect postoperative adverse events. Although correlated to frailty (p = 0.004), multivariable regression analysis identified malnutrition as independent risk factor for reoperation (OR 2.6, 95% CI 1.1-6.2) and wound healing disorders (OR 7.1, CI 1.9-26).Interpretation - Malnutrition is common among geriatric patients undergoing elective orthopedic surgery and represents an independent risk factor for postoperative adverse events.