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.

Alteración de las vitaminas en pacientes con cáncer: un estudio comparativo prospectivo / Vitamins disturbance in cancerous patients: A prospective comparison study

Cancers are a complex diseases that involve abnormal cell growth pattern and it is the leading cause of morbidity and mortality worldwide. The chemotherapy is one of the most common treatments for cancer. Cancer cause malnutrition and deficiencies of vitamins, in addition chemotherapy causes those deficiencies by induced anorexia, stomatitis, and alimentary tract disturbances. The study aims to determined and assessed the levels of serum vitamins (A, B12, B6, B9, E, D, and K) before and after chemotherapy administration. A prospective study carried out on newly diagnosed cancerous patients whom receiving chemotherapy. Fifty patients enrolling and recruited. Follow up will be recorded after the first, third, and sixth cycles of chemotherapy. The panel used for evaluation of vitamins concentration included the following six kits: Human Vitamin AV, E, VB6, B12, VD3 DIY, VK and FOLR3 ELISA kits. 38 females and 12 males included, with mean age was 48.35±15.28 years. The mostly distributed age group was belong to fifth decades. The mean body mass index (BMI) was 33.12±5.51 m2 /Kg. The majority of the sample treated were breast cancers females about 26(52%). Regarding chemotherapy regimens, the AC+Taxen protocol was mostly used. The mean level of vitamin A found to be declined to the half from (69.23±24.66 µg/dL) at C0 to (35.73±18.89 µg/dL) at C6. Normal mean value of vitamin B12 level was presented in the most of patients pre- and post- chemotherapy. Vitamin B6 concentrations in the most of patients risen by double post-chemotherapy. Vitamin D concentration not changed in pre- and post- chemotherapy. We observed a statistically significant differences among vitamin E concentration pre- and post- chemotherapy (ANOVA=3.213, P=0.033). In this study, most of patients pre-chemotherapy period had normal folate level, whereas it to decreased from (6.23±3.12 ng/mL) to reached (3.33±2.72 ng/mL) after anti-cancer, with strong statistically significant differences (ANOVA=6.56, P=0.012). In addition, vitamin K concentration was unchanged throughout chemotherapy cycles. Many factors in cancerous participants lead to vitamins deficiencies. Several vitamins remained within normal concentration throughout anti-cancer course might be due to vitamins supplement taken by persons during their regimens. Almost always vitamins concentration dropped during cycles, but still within normal value, except vitamin E, which was deficient in last cycle of chemotherapy. Vitamins replacement are mandatory for substitution dropping level because off those are essential for many body processes and regulation.

Nutritional neuropathies.

Neuropathies associated with nutritional deficiencies are routinely encountered by the practicing neurologist. Although these neuropathies assume different patterns, most are length-dependent, sensory axonopathies. Cobalamin deficiency neuropathy is the exception, often presenting with a non-length-dependent sensory neuropathy. Patients with cobalamin and copper deficiency neuropathy characteristically have concomitant myelopathy, whereas vitamin E deficiency is uniquely associated with a spinocerebellar syndrome. In contrast to those nutrients for which deficiencies produce neuropathies, pyridoxine toxicity results in a non-length-dependent sensory neuronopathy. Deficiencies occur in the context of malnutrition, malabsorption, increased nutrient loss (such as with dialysis), autoimmune conditions such as pernicious anemia, and with certain drugs that inhibit nutrient absorption. When promptly identified, therapeutic nutrient supplementation may result in stabilization or improvement of these neuropathies.

Micronutrient Depletion in Heart Failure: Common, Clinically Relevant and Treatable.

Heart failure (HF) is a chronic condition with many imbalances, including nutritional issues. Next to sarcopenia and cachexia which are clinically evident, micronutrient deficiency is also present in HF. It is involved in HF pathophysiology and has prognostic implications. In general, most widely known micronutrients are depleted in HF, which is associated with symptoms and adverse outcomes. Nutritional intake is important but is not the only factor reducing the micronutrient availability for bodily processes, because absorption, distribution, and patient comorbidity may play a major role. In this context, interventional studies with parenteral micronutrient supplementation provide evidence that normalization of micronutrients is associated with improvement in physical performance and quality of life. Outcome studies are underway and should be reported in the following years.

Impact of Biliopancreatic Limb Length (70 cm vs 120 cm), with Constant 150 cm Alimentary Limb, on Long-Term Weight Loss, Remission of Comorbidities and Supplementation Needs After Roux-En-Y Gastric Bypass: a Prospective Randomized Clinical Trial.

BACKGROUND: The best alimentary and biliopancreatic limb (BPL) lengths in the Roux-en-Y gastric bypass (RYGB) still remain unclear. The aim of this study was to compare the effect of a BPL of 70 vs 120 cm, with a constant AL of 150 cm on long-term weight loss, remission of comorbidities, and supplementation needs after RYGB. PATIENTS AND METHODS: A prospective randomized study of morbidly obese patients undergoing RYGB was performed. Patients were randomized into two groups: those patients undergoing RYGB with a BPL of 70 cm (BPL 70 cm) and those ones undergoing RYGB with a BPL of 120 cm (BPL 120 cm). BMI, excess BMI loss (EBMIL), remission of comorbidities and specific vitamin and mineral supplementation needs at 1, 2, and 5 years were analyzed. RESULTS: Two hundred fifty-three patients were included in each group. There were no significant differences in BMI, EBMIL and the remission of diabetes mellitus, hypertension, and dyslipidemia between groups at 1, 2, and 5 years after surgery. Patients from group BPL 120 cm required greater specific supplementation of vitamin B12, folic acid, and vitamin A during all the follow-up. CONCLUSION: A RYGB with 120 cm BPL does not achieve greater weight loss or remission of comorbidities than a RYGB with 70 cm BPL but is associated with greater deficiencies of vitamin B12, vitamin A, and folic acid. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03607305. https://clinicaltrials.gov/.

Nutritional Status in the First 2 Years of Life in Cystic Fibrosis Diagnosed by Newborn Screening.

OBJECTIVE: To evaluate nutritional status and associated factors in a cystic fibrosis (CF) cohort diagnosed by newborn screening and followed up to month 24. METHODS: A prospective longitudinal multicenter study assessing nutritional status according to pancreatic status, feeding modalities, prescriptions, pulmonary outcome, and biological nutritional parameters. RESULTS: One hundred and five infants were recruited and 99 completed the study. Nutritional care management prevented undernutrition and stunting in those with exocrine pancreatic sufficiency (EPS), but affected (13/87) 15% and (21/86) 24%, respectively, of infants with exocrine pancreatic insufficiency (EPI). The logistic regression model found a positive association between both weight and length z scores "at risk" at month 24, and initial pulmonary symptoms (odds ratio [OR] 0.06, P < 0.01 and OR 0.08, P < 0.01, respectively); these symptoms were less frequent when age at first visit was earlier than 1.2 months (33% vs 67%, P = 0.02); stunting was also associated with high-calorie density intake and Staphylococcus aureus (OR 0.05, P = 0.01 and OR 0.17, P < 0.01). Pulmonary outcome did not differ according to pancreatic status; breast-feeding for at least 3 months delayed first acquisition of Pseudomonas aeruginosa. Despite sodium and fat-soluble vitamin supplementation, half of both cohorts had low urinary sodium output and half of the EPI cohort had low vitamin D levels. CONCLUSIONS: Our data shed light on the fact that stunting was more frequent than undernutrition, while both parameters involved only patients with pancreatic insufficiency. Modalities of feeding were not associated with nutritional status; breast-feeding may provide some protection against acquisition of P aeruginosa.

Suplementación con vitamina D en las edades pediátricas / Supplementation with vitamin D in children

Introducción: el sol constituye la fuente principal de vitamina D, las últimas décadas se han caracterizado por una menor exposición al sol de la población general, lo cual ha posibilitado que el déficit de vitamina D reaparezca como un problema de salud mundial. Esta situación ha generado grandes controversias internacionales sobre el uso de suplementos de vitamina D en la edad pediátrica. Objetivo: reflexionar sobre las recomendaciones internacionales de suplementación con vitamina D en las edades pediátricas, ajustándolas al contexto cubano. Método: revisión documental. Se utilizaron motores de búsqueda (Google Académico, Springer Link, Microsoft Academic y SciELO - Scientific Electronic Library Online), y se emplearon las bases de datos disponibles en la Biblioteca Virtual de Salud, se revisaron evidencias científicas y se realizaron recomendaciones basadas en las mismas. Conclusiones: existen factores que llevan implícito un incremento del riesgo potencial de déficit de vitamina D. En Cuba se destacan la actualización de las medidas de fotoprotección para las edades pediátricas, la prevalencia de fototipos altos y el incremento de la obesidad en la población infantil. Se realizaron 9 recomendaciones para garantizar un aporte adecuado de vitamina D a los niños y adolescentes cubanos, el equivalente a 400 UI de vitamina D para menores de un año y 600 UI para los mayores de esa edad que pertenezcan a grupos de riesgo para esta hipovitaminosis(AU)

Introduction: The sun is the main source of vitamin D. The last decades have been characterized by a lower exposure to the sun by the general population, what has caused the recurrence of vitamin D deficit as a world health problem. This situation has given rise to international controversies on the use of vitamin D supplements in children. Objective: To reflect on the international recommendations about the use of vitamin D supplements in children, meeting the Cuban context. Method: A bibliographic review was carried out, using the search engines Scholar Google, Springer Link, Microsoft Academic and SciELO - Scientific Electronic Library Online, as well as databases available at the Health Virtual Library. Scientific evidences were checked and recommendations based on them were made. Conclusions: There are factors that have an implicit increasing risk of vitamin D deficit. In Cuba some important features stand out, as the updating of photoprotection in children, the prevalence of high phototypes and the increase of obesity in the child population. Nine recommendations were carried out to guarantee an adequate contribution of vitamin D to the Cuban children and adolescents, an equivalent of 400 IU of vitamin D for children younger tan one year and 600 IU for the older ones who belong to risk groups for this type of hypovitaminosis(AU)

Dietary supplements and disease prevention - a global overview.

Dietary supplements are widely used and offer the potential to improve health if appropriately targeted to those in need. Inadequate nutrition and micronutrient deficiencies are prevalent conditions that adversely affect global health. Although improvements in diet quality are essential to address these issues, dietary supplements and/or food fortification could help meet requirements for individuals at risk of deficiencies. For example, supplementation with vitamin A and iron in developing countries, where women of reproductive age, infants and children often have deficiencies; with folic acid among women of reproductive age and during pregnancy; with vitamin D among infants and children; and with calcium and vitamin D to ensure bone health among adults aged ≥65 years. Intense debate surrounds the benefits of individual high-dose micronutrient supplementation among well-nourished individuals because the alleged beneficial effects on chronic diseases are not consistently supported. Daily low-dose multivitamin supplementation has been linked to reductions in the incidence of cancer and cataracts, especially among men. Baseline nutrition is an important consideration in supplementation that is likely to modify its effects. Here, we provide a detailed summary of dietary supplements and health outcomes in both developing and developed countries to help guide decisions about dietary supplement recommendations.

[The first pillar of patient blood management. Types of anemia and diagnostic parameters]. / Primer pilar del "Patient Blood Management". Tipos de anemia y parámetros diagnósticos.

Patient Blood Management (PBM) is the design of a personalized, multimodal multidisciplinary plan for minimizing transfusion and simultaneously achieving a positive impact on patient outcomes. The first pillar of PBM consists of optimizing the erythrocyte mass. The best chance for this step is offered by preoperative preparation. In most cases, a detailed medical history, physical examination and laboratory tests will identify the cause of anemia. A correct evaluation of parameters that assess the state and function of iron, such as ferritin levels, and the parameters that measure functional iron, such as transferrin saturation and soluble transferrin receptor levels, provide us with essential information for guiding the treatment with iron. The new blood count analyzers that measure hypochromia (% of hypochromic red blood cells and reticulocyte hemoglobin concentrations) provide us useful information for the diagnosis and follow-up of the response to iron treatment. Measuring serum folic acid and vitamin B12 levels is essential for treating deficiencies and thereby achieving better hemoglobin optimization.

[Fat-soluble vitamins supplementation in patients with cystic fibrosis: is enough Aquadek's®?]. / Suplementacion con vitaminas liposolubles en pacientes con fibrosis quistica: ¿es suficiente con Aquadek's®?

INTRODUCTION AND OBJECTIVE: Evaluate the safety and efficacy of a novel polyvitaminic (Aquadek's®) in patients with Cystic Fibrosis (CF). MATERIAL AND METHODS: Prospective, longitudinal and non-randomized study. CF patients with pancreatic insufficiency and clinically stable were given Aquadek's® (two chewable tablets) daily for 12 months. Serum levels of retinol, beta-carotene, 25 OH vitamin D and α-tocopherol were evaluated twelve months before, at baseline and 12 months after. STATISTICAL ANALYSIS: paired t tests. RESULTS: 28 patients aged 6 to 39 years (median 18.5 years) were included. Aquadek's® supplementation led to an increase in vitamin A dose and a decrease in the number of tablets administered. At baseline, 89% had at least one vitamin deficiency (61% pro-Vitamin A and 54% vitamin D). After one year, serum beta-carotene levels were increases 160 (95% CI 98-222) mcg/l (p <0.001) and decreased the percentage of patients with pro-vitamin A deficiency 46% (95% CI 22-64) (p <0.001). The proportion of patients with vitamin D insuficiency increased 18%(95% CI 2-32) (p =0.025). In any case serum levels exceeded the upper limits used to assess the risk of toxicity.Conclusions: Two daily Aquadek's® chewable tablets are safe and effective for maintaining vitamin A and E status of CF patients older than 6 years, although it is insufficient to normalize serum 25OHvitaminD according to the current recommendations for this disease.

Introducción y objetivo: Conocer si la suplementación un nuevo polivitamínico (Aquadek´s®) durante 12 meses es segura y eficaz en pacientes con Fibrosis Quística (FQ). Material y Métodos: Estudio prospectivo, longitudinal y no controlado en pacientes con FQ insuficientes pancreáticos, clínicamente estables, que recibieron suplementación con Aquadek´s® (2 comprimidos masticables) durante 12 meses en lugar de su suplementación habitual. Se evaluaron niveles séricos de retinol, betacarotenos, 25 OH vitamina D y α-tocoferol un año antes, al inicio y tras un año de tratamiento. Análisis estadístico: Pruebas t para datos pareados. Resultados: Se incluyeron 28 pacientes entre 6 y 39 años (mediana 18,5 años). La suplementación con Aquadek´s® supuso un incremento en la dosis de vitaminas A y una disminución del número de comprimidos administrados. Al inicio, un 89% presentaban algún tipo de déficit vitamínico: (61% pro-Vitamina A y 54% vitamina D). Tras un año, se produjo un incremento de los niveles de betacarotenos: 160 mcg/l (IC 95% 98-222) (p.

[Vitamins and oxidative stress].

The central and local stress limiting systems, including the antioxidant defense system involved in defending the organism at the cellular and systemic levels from excess activation response to stress influence, leading to damaging effects. The development of stress, regardless of its nature [cold, increased physical activity, aging, the development of many pathologies (cardiovascular, neurodegenerative diseases, diseases of the gastrointestinal tract, ischemia, the effects of burns), immobilization, hypobaric hypoxia, hyperoxia, radiation effects etc.] leads to a deterioration of the vitamin status (vitamins E, A, C). Damaging effect on the antioxidant defense system is more pronounced compared to the stress response in animals with an isolated deficiency of vitamins C, A, E, B1 or B6 and the combined vitamins deficiency in the diet. Addition missing vitamin or vitamins restores the performance of antioxidant system. Thus, the role of vitamins in adaptation to stressors is evident. However, vitamins C, E and beta-carotene in high doses, significantly higher than the physiological needs of the organism, may be not only antioxidants, but may have also prooxidant properties. Perhaps this explains the lack of positive effects of antioxidant vitamins used in extreme doses for a long time described in some publications. There is no doubt that to justify the current optimal doses of antioxidant vitamins and other dietary antioxidants specially-designed studies, including biochemical testing of initial vitamin and antioxidant status of the organism, as well as monitoring their change over time are required.

The influence of deficiencies of essential trace elements and vitamins on the course of Crohn's disease.

In patients with Crohn's Disease (CD), malnutrition is frequently observed and is an important complication, frequently associated with nutritional deficiencies, especially vitamins (both water- and fat-soluble) and essential trace elements. It is often a result of the disease activity, poor oral intake and/or restrictive diets. Nutrition plays an important role in disease management and helps to maintain remission in CD patients. Deficiencies occur in patients with active Crohn's disease, and also in those in remission. Specific supplementation of vitamins and micro- and macronutrients might be helpful or even necessary in this group of patients. This review outlines the most frequent nutritional deficiencies and their complications in relation to the Crohn's Disease Activity Index, and provides an overview of therapeutic perspectives for CD patients in adult patients with inflammatory bowel disease (IBD). Biological therapy, which is being used with increasing frequency, seems not only to mitigate the inflammatory process in the gastrointestinal tract, but also has significant impact on the nutritional status of patients with Crohn's disease.

Invasive pneumonia and septic shock in infants as a presentation of cystic fibrosis with vitamin-deficiency.

Herein we describe three infants with the rare presentation of pneumonia with septic shock as their initial medical encounter leading to the diagnosis of cystic fibrosis (CF). At the time of their presentation all three children had significant nutritional deficiency. We initiated an aggressive treatment regimen including nutritional supplementation which resulted in improvement in their pulmonary status and no further recurrences. This series highlights the possible presentation of CF in infancy as a life-threatening invasive infection of Staphylococcus aureus or Pseudomonas aeruginosa. It also supports neonatal screening and emphasizes the role of early attention to nutritional status and vitamin supplementation.

Evaluación y correlación de variables bioquímicas, antropométricas y de consumo de riboflavina, hierro y vitamina A en escolares venezolanos / Evaluation and correlation of biochemical, anthropometrical and consumption variables of riboflavin, iron and vitamin a in scholars from venezuela

El objetivo fue evaluar el estado de riboflavina, hierro y vitamina A de un grupo de escolares de Caracas, correlacionando variables bioquímicas, de composición corporal y de consumo de energía y nutrientes. Se estudiaron 69 niños con edades comprendidas entre 6 y 8 años a los que se les determinó estrato socioeconómico, consumo de alimentos, adecuación de consumo y fórmula dietética. Se tomaron medidas antropométricas y una muestra de sangre para la determinación de hemoglobina y hematocrito, así como concentraciones plasmáticas de riboflavina por método enzimático, retinol por HPLC, hierro por colorimetría y ferritina por ELISA. Los escolares tuvieron una dieta monótona en la que los cuatro alimentos más consumidos fueron cereales. La dieta resultó inadecuada en vitamina A (48%), hierro (39%), riboflavina (6%) y vitamina B6 (80%). Las determinaciones antropométricas mostraron un importante porcentaje de desnutrición actual (19%), aunque la mayoría presentó estado nutricional antropométrico y composición corporal normales. Las determinaciones hematológicas mostraron deficiencias de riboflavina (16%), retinol (57%), hierro (67%) y anemia (14%). En conclusión, la dieta fue poco variada, deficitaria en calorías, vitamina B6, vitamina A, proteínas y hierro y excesiva en riboflavina, con un estado nutricional antropométrico y composición corporal normales. Los datos de consumo y adecuación de la dieta se correlacionaron con las deficiencias encontradas en pruebas hematológicas, mientras que los datos antropométricos no fueron marcadamente afectados, aunque hubo correlación entre las variables área muscular y área grasa, y el consumo de energía, proteínas, grasa, hierro y riboflavina(AU)

The objective was to evaluate the status of riboflavin, iron and vitamin A in a group of school children from Caracas, correlating biochemical, body composition and consumption data. The sample included 69 scholars aged 6 to 8 years whose socio economic status, food consumption patterns and adequacy as well as dietetic formulae were determined. Anthropometric measures were recorded and a blood sample was taken to determine hemoglobin, hematocrit and plasmatic concentrations of riboflavin by an enzymatic method, retinol by HPLC, iron by a colorimetric method and ferritin by ELISA. The scholars had a monotonous diet and the 4 most consumed food items were cereals. The diet resulted inadequate in vitamin A (48%), iron (39%), riboflavin (6%) and vitamin B6 (80%). Anthropometric evaluation showed an important percentage of recent undernutrition (19%), although most of the individuals had a nutritional anthropometric state and a body composition within normal ranges. Hematological determinations showed deficiencies of riboflavin (16%), retinol (57%), iron (67%) and anemia (14%). In conclusion, the diet was monotonous, deficient in calories, vitamin B6, vitamin A, proteins and iron and excessive in riboflavin, with inadequate anthropometric and body composition status. Data on consumption and diet adequacy correlated with results from hematological tests, while anthropometric data was not markedly affected, although there was a linear correlation between muscular and fat areas with energy, protein, fat, iron and riboflavin consumption(AU)

Oral absorbable fat-soluble vitamin formulation in pediatric patients with cholestasis.

OBJECTIVE: Fat-soluble vitamin (FSV) deficiencies are common complications in pediatric patients with chronic cholestasis. The aim of the present study was to evaluate the status of FSV deficiencies in patients under present practice and to test the effect of an oral, absorbable, fat-soluble vitamin formulation (OAFSV) in these patients. METHODS: We recruited a total of 23 pediatric patients receiving conventional FSV supplementation in a single medical center, with diagnosis of biliary atresia (10), progressive familial intrahepatic cholestasis (9), Alagille syndrome (2), and other conditions (2). Ten patients switched to OAFSV and continued for 3 months. Plasma levels of vitamins A, D, and E and an international normalized ratio (INR) for prothrombin time (PT), a surrogate marker for vitamin K deficiency, were measured. RESULTS: The proportion of patients with FSV A, D, E, and K deficiencies under conventional supplementation was 73.9%, 81.8%, 91.3%, and 20.0%, respectively. In patients with total bilirubin levels ≥3.0  mg/dL, the proportion of at least 1 FSV deficiency was 100%; and the deficiency rates of vitamin A, D, E, and K were 78.6%, 100.0%, 100.0% and 21.4%, respectively. Of the 10 patients receiving standard daily dose of OAFSV for 3 months, no adverse events or overdose effects were found. The rates of vitamin A, D, and E deficiency in the patients receiving OAFSV decreased from 80.0%, 100%, and 100%, respectively, to 70.0%, 60.0%, and 60.0% after 3 months of oral supplementation. CONCLUSIONS: High rates of FSV deficiency were found in pediatric patients with chronic cholestasis under present follow-up. OAFSV supplementation is safe and potentially effective in pediatric patients with cholestasis.

Adrenal insufficiency following bariatric surgery.

A 35-year-old woman with morbid obesity and amenorrhoea underwent a bilo-pancreatic diversion (BPD). Surgery was successful with good weight loss, restoration of menstruation and almost immediately she conceived for the first time. She was commenced on routine vitamin supplements after surgery but failed to attend follow-up clinic. Five years later, she presented with limb girdle pains, lethargy, night blindness, skin pigmentation, amenorrhoea and dizziness. She had stopped taking supplements prescribed after the surgery. Investigations showed severe vitamin A and D deficiency along with iron and calcium deficiency. Her cholesterol was low at 3.5 mmol L⁻¹. Despite aggressive vitamin replacement, she continued to complain of lethargy and dizziness. Subsequently, three short adrenocorticotropic hormone-stimulation tests were suboptimal (basal cortisol: 196, 185 and 223 nmol L⁻¹; 30 min cortisol: 421, 453 and 435 nmol L⁻¹). She was subsequently commenced on adrenal replacement and her symptoms resolved and she conceived. We describe for the first time in the literature the unexpected finding of adrenal insufficiency following a BPD.

Vitamins - wrong approaches.

Deficiencies of essential nutrients have been responsible for many epidemic outbreaks of deficiency diseases in the past. Large observational studies point at possible links between nutrition and chronic diseases. Low intake of antioxidant vitamins e. g. have been correlated to increased risk of cardiovascular diseases or cancer. The main results of these studies are indications that an intake below the recommendation could be one of the risk factors for chronic diseases. There was hardly any evidence that amounts above the RDA could be of additional benefit. Since observational studies cannot prove causality, the scientific community has been asking for placebo-controlled, randomized intervention trials (RCTs). Thus, the consequences of the epidemiological studies would have been to select volunteers whose baseline vitamin levels were below the recommended values. The hypothesis of the trial should be that correcting this risk factor up to RDA levels lowers the risk of a disease like CVD by 20 - 30 %. However, none of the RCTs of western countries was designed to correct a chronic marginal deficiency, but they rather tested whether an additional supplement on top of the recommended values would be beneficial in reducing a disease risk or its prognosis. It was, therefore, not surprising that the results were disappointing. As a matter of fact, the results confirmed the findings of the observational studies: chronic diseases are the product of several risk factors, among them most probably a chronic vitamin deficiency. Vitamin supplements could only correct the part of the overall risk that is due to the insufficient vitamin intake.