Tocopherols, tocotrienols and tocomonoenols: Many similar molecules but only one vitamin E.

The aim of this article is to correct a very general error in scientific articles, in textbooks and in the Internet that has become an accepted fact. In this literature, the term "vitamin E″ is used for several similar molecules (both tocopherols and tocotrienols) that have never been shown to have vitamin property, i.e. a protective effect against the human deficiency disease. In fact, the name "vitamin E″ should only be used to define molecules that prevent the human deficiency disease "Ataxia with Vitamin E Deficiency" (AVED). Only one such molecule is known, α-tocopherol. This error may confuse consumers as well as medical doctors, who prescribe vitamin E without realizing that the current use of the name includes molecules of unknown, if not unwanted functions.

Multiple unexplained fractures in infants and child physical abuse.

When an infant presents with X-rays showing multiple unexplained fractures in various stages of healing (MUFVSH), the child is usually diagnosed with child abuse based on criteria of the Academy of Pediatrics' Committee on Child Abuse and Neglect (AAPCCAAN). Almost always, the infant is subsequently removed from the home and civil or criminal proceeding commence. It may be that healing infantile rickets or other poorly understood metabolic bone disorders of infancy are responsible for these x-rays. Activated vitamin D is a seco-steroid hormone, whose mechanism of action is genetic regulation. Lack of it can result in musculoskeletal defects known as rickets. Low calcium can also cause rickets. However, it is clear that experts for the state believe that the x-rays in these cases are so definitive as to be pathognomonic for child abuse. Therefore, if the caregivers deny abusing their infants, experts following American Academy of Pediatric's Committee on Child Abuse and Neglect. guidelines are essentially claiming that x-rays showing multiple unexplained fractures in various stages of healing are lie detector tests. However, it is not widely appreciated that the gold standard for the diagnosis of rickets is a bone biopsy, not x-rays, as radiologists miss biopsy proven rickets 80% of the time; that is, 4 out of 5 infants with rickets will have normal x-rays. In this article we provide reports of two cases and their outcomes. We discuss information about healing infantile rickets and an example of common sense medical conclusions in these cases. This information could lead to a significant reduction in the number of innocent parents having their infant removed or sent to prison.

Oral Supplementation of Parturient Mothers with Vitamin D and Its Effect on 25OHD Status of Exclusively Breastfed Infants at 6 Months of Age: A Double-Blind Randomized Placebo Controlled Trial.

BACKGROUND: Exclusively breastfed infants are at increased risk of vitamin D deficiency and many lactating mothers have been found deficient in 25OHD stores. OBJECTIVE: To compare serum vitamin D levels in exclusively breastfed infants at 6 months of age with or without oral supplementation of 600,000 IU of vitamin D3 to mothers in early postpartum period. METHODS: Exclusively breastfeeding term parturient mothers were randomized 24-48 hours following delivery to receive either 600,000 IU of vitamin D3 (Cholecalciferol) over 10 days in a dose of 60,000 IU/day or placebo. 25OHD levels were measured by Radio Immuno Assay method at recruitment and after 6 months in all mothers and their infants. Urinary calcium and creatinine ratio was measured to monitor adverse effects of vitamin D3 in both mothers and infants at 14 weeks and 6 months of age. X-ray of both wrists in anteroposterior view and serum alkaline phosphatase of infants were done in both groups at 6 months of age to look for evidence of rickets. RESULTS: Maternal profile was similar in intervention (A) and control (B) groups. Mothers' serum 25OHD levels at recruitment were also similar being 16.2 ± 9.3 ng/mL in group A and 14.1 ± 7.1 ng/mL in group B. After 6 months, 25OHD levels were 40.3 ± 21.6 and 22.9 ± 20.1 ng/mL in group A and group B mothers (p ≤ 0.00), respectively. The serum 25OHD levels in cord blood were 9.9 ± 5.7 and 8.9 ± 5.1 ng/mL, respectively, in infants born to mothers in intervention and control groups (p = 0.433). At 6 months of age, the serum 25OHD levels significantly (p < 0.00) raised to 29.1 ± 14.6 ng/mL in infants of group A compared to those of group B (15.7 ± 17.7 ng/mL). Four infants developed radiological rickets at 6 months of age, two infants each in intervention group and study group. As against 10 infants in the control group (16.94%), no infant in the study group had biochemical rickets. Urinary calcium and creatinine ratio in mothers and infants at 14 weeks and 6 months of age in both intervention and study group was within normal limits, indicating there was no adverse effects of oral administration of 600,000 IU of vitamin D3. CONCLUSION: Serum 25OHD levels of exclusively breastfed infants significantly rise at 6 months of age when their mothers are orally supplemented with 60,000 IU of vitamin D3 daily for 10 days in the early postpartum period in comparison to infants of vitamin D3 unsupplemented mothers.

Sex-related differences in the skeletal phenotype of aged vitamin D receptor global knockout mice.

The role of the vitamin D receptor (VDR) in maintaining skeletal health appears to be complex and dependent on the physiological context. Global Vdr deletion in a mouse model (Vdr-/-) results in hypocalcemia, secondary hyperparathyroidism and bone features typical of vitamin D-dependent rickets type II. When weanling Vdr-/- mice are fed a diet containing high levels of calcium, phosphorus and lactose, termed the rescue diet, normalisation of serum calcium, phosphate and parathyroid hormone levels results in prevention of rickets at 10 weeks of age. However, 17 week old male Vdr-/- mice, fed the rescue diet, have been reported as osteopenic due to a decrease in bone formation when compared to wild type mice. We now report confirmation of this finding with further data on the effect of the rescue diet on appendicular and axial skeletal structures in male and female Vdr-/- mice at 26 weeks of age compared to Vdr+/- controls. All Vdr-/- mice were normocalcemic with no evidence of any mineralization defect. However, male Vdr-/- mice exhibited significantly reduced mineral in femoral and vertebral bones when compared to control littermate Vdr+/- mice, consistent with the previously reported data. In contrast, 26-week-old female Vdr-/- mice demonstrated significantly increased femoral trabecular bone volume although there was decreased vertebral trabecular bone volume, similar to males, and femoral cortical bone volume was unchanged. Thus, the Vdr-/- mouse model displays sex- and site-specific differences in skeletal structures with long-term feeding of a rescue diet. Although the global Vdr-/- ablation does not permit the determination of skeletal mechanisms producing these differences, these data confirm skeletal changes even when fed the rescue diet.

An update on vitamin D deficiency and at risk groups.

Vitamin D is required for healthy bones. We need sunlight and good renal and liver function for the synthesis of vitamin D, although it can also be taken in diet. Severe deficiency causes the bone diseases rickets and osteomalacia. Supplementation with vitamin D can help prevent low birth weight and non-vertebral fractures. Roles for vitamin D in other aspects of health are controversial.

Calcium and vitamin D metabolism in children in developing countries.

Low dietary calcium intakes and poor vitamin D status are common findings in children living in developing countries. Despite many of the countries lying within the tropics and subtropics, overcrowding, atmospheric pollution, a lack of vitamin D-fortified foods, and social customs that limit skin exposure to sunlight are major factors in the development of vitamin D deficiency. Low dietary calcium intakes are typically observed as a consequence of a diet limited in dairy products and high in phytates and oxalates which reduce calcium bioavailability. Calcium intakes of many children are a third to a half of the recommended intakes for children living in developed countries, yet the consequences of these low intakes are poorly understood as there is limited research in this area. It appears that the body adapts very adequately to these low intakes through reducing renal calcium excretion and increasing fractional intestinal absorption. However, severe deficiencies of either calcium or vitamin D can result in nutritional rickets, and low dietary calcium intakes in association with vitamin D insufficiency act synergistically to exacerbate the development of rickets. Calcium supplementation in children from developing countries slightly increases bone mass, but the benefit is usually lost on withdrawal of the supplement. It is suggested that the major effect of calcium supplementation is on reducing the bone remodelling space rather than structurally increasing bone size or volumetric bone density. Limited evidence from one study raises concerns about the use of calcium supplements in children on habitually low calcium intakes as the previously supplemented group went through puberty earlier and had a final height several centimetres shorter than the controls.

Radiographic changes in nutritional ricket hips in children in response to treatment.

PURPOSE: To review radiographic changes in the proximal femurs of children of different ages during the course of treatment for nutritional rickets. METHODS: Pelvic radiographs of 161 children aged ≤ 13 years with nutritional rickets were retrospectively reviewed. Patients were treated with dietary counselling and vitamin D and calcium supplementation. Patients were followed up at week 3 and thereafter at a 2-month interval until ulnar convexity was achieved. Sequential radiographs of the hips in children of different ages were reviewed for each growth plate in terms of (1) the direction of growth, (2) active areas, (3) contribution of growth, and (4) the structure of the epiphysis. Radiographs were superimposed for comparison by matching the triradiate cartilage and the ischial portion of the obturator foramen. RESULTS: The direction of growth of the growth plates was from the physeal plate that is the longitudinal growth plate of the neck (LGP), the femoral neck isthmus (FNI), and the trochanteric growth plate (TGP) to the diaphyseal region, and from the perichondrium to the ossification centre in the proximal femoral epiphysis. Before the age of one year, the growth zone of the proximal femur was homogenous, with no differentiation between the LGP, FNI, and TGP. By the age of 2 years, the differentiation was more clearly established; the FNI was usually smaller than the TGP and LGP. By the age of 3 years, the FNI became prominent and the TGP remained small. By the age of 4 years, the ossification centre of the greater trochanter appeared, and the LGP extended medially as a medial overhang (MOH). During the children's growth, the LGP, FNI, or TGP remained active to a variable extent and were distinct until the age of 6 years. Gradually, the periphery of the LGP became less active than the centre of the LGP and gave rise to the 'eye sign'. The MOH generally ceased to be active beyond the age 9 years. By the age of 12 years, the TGP and FNI were minimally active and only the centre of the LGP remained active. CONCLUSION: The mineralisation process of healing rickets provides a useful biological marker for patterns of growth. Knowledge of the quantitative contribution of various growth plates of the proximal femur in childhood may increase the understanding of the pathomechanism of hip deformations.

Pneumopatía raquítica: el retorno de una entidad clínica del pasado / Rickets pneumopathy: the return of a clinical entity of the past

Introducción. El raquitismo era una enfermedad poco frecuente en los países desarrollados; no obstante, debido a los cambios culturales y los episodios migratorios, vuelve a ser una patología emergente. La neumopatía raquítica se basa en el compromiso de la función respiratoria por una parrilla costal flexible y débil secundaria a una mineralización deficiente de los huesos en crecimiento. Se añade una mayor susceptibilidad a las infecciones y cambios del parénquima pulmonar. Caso clínico. Se presenta el caso de una lactante de 7 meses de padres subsaharianos que consulta por fiebre y dificultad respiratoria. En la inspección destaca un tórax delgado y acampanado, con una depresión transversal en la unión tóraco-abdominal (surco de Harrison), y se palpa craneotabes, por lo que se realiza un estudio que muestra: parathormona y fosfatasa alcalina elevadas, vitamina 25-(OH)-D3 baja, calcio, fósforo y función renal normales. La radiografía de muñeca izquierda muestra ensanchamiento de metáfisis y edad ósea retrasada. Comentarios. Hay descritos casos con presentaciones atípicas, como convulsiones hipocalcémicas, tetania o fractura patológicas, pero hay que remontarse a publicaciones de hace cuatro décadas para encontrar en la literatura artículos sobre patología respiratoria asociada a raquitismo. Cabe resaltar la importancia de la detección precoz de los síntomas y signos en la población de riesgo para disminuir la incidencia de raquitismo mediante una profilaxis adecuada (AU)

Introduction. Rickets is an extremely rare disease in high-income countries; however, cultural changes and migratory phenomena have led to a resurgence of this condition. Patients with rickets pneumopathy have impaired respiratory function resulting from dysfunctional rib cage due to insufficient bone mineralization during growth. In addition, patients have an increased susceptibility to infections and alterations in the lung parenchyma. Case Report. A 7-month-old infant born to Sub-Saharan parents presented with fever and respiratory distress. Physical examination revealed a bell-shaped, narrow thorax, with a horizontal groove along the lower border of the chest (Harrison groove) and palpable craniotabes. Additional evaluation showed elevated levels of parathyroid hormone and alkaline phosphatase, vitamin 25-(OH)-D3 deficiency, and normal calcium, phosphorus, and renal function. Wrist X-ray revealed widening of the metaphysis and delayed bone age. Comments. Several atypical presentations of rickets have been reported, such as hypocalcemic seizures, tetany, or pathological fractures, and yet rickets-associated respiratory diseases have seldom been reported in the last four decades. Early detection of symptoms and signs in populations at risk is paramount to reduce the incidence and severity of rickets and to provide adequate prevention and treatment (AU)

How vitamin D works on bone.

Vitamin D is important for the normal development and maintenance of bone. The elucidation of the vitamin D activation pathway and the cloning of the vitamin D receptor have advanced our understanding of the actions of vitamin D on bone. The preponderance of evidence indicates that 1,25(OH)2D3 enhances bone mineralization through its effects to promote calcium and phosphate absorption. Although 1,25(OH)2D3 stimulates bone resorption in vitro, treatment in vivo can prevent bone loss and fracture through several potential mechanisms. The development of vitamin D analogues has provided new therapeutic options for increasing bone mineral density and reducing fractures.

Oxidant/antioxidant system markers and trace element levels in children with nutritional rickets.

OBJECTIVE: To determine the oxidative stress and trace element levels in vivo in patients with nutritional rachitism associated with vitamin D deficiency. MATERIALS AND METHOD: A total of 30 patients, 18 males and 12 females, were included in the study. Age, sex, medical history, vital, and physical examination findings of each patient documented at presentation were recorded. Serum calcium, phosphorus, alkaline phosphatase, parathormone, and 25-OH vitamin D levels, as well as oxidant and antioxidant system parameters and trace element levels were studied. After being diagnosed with rachitism, the patients were administered a single dose of 300,000 IU vitamin D by intramuscular injection. The same analyses were repeated post-treatment. Thirty children with normal anthropometric measurements were included as the control group. The analyses described above were performed only once for the control group. RESULTS: Serum calcium, phosphorus, alkaline phosphatase, parathormone, and 25-OH vitamin D levels were different between the controls and children in the patient group (p<0.001). Analysis of trace element levels demonstrated markedly lower pretreatment zinc levels for the patient group compared to the controls, with a statistically significant difference (p=0.001). Comparison of pretreatment oxidant and antioxidant system markers between the patient and control groups demonstrated higher values for vitamin C, ß-carotene, reduced glutathione, and superoxide dismutase in the control group, whereas MDA was higher in the patient group. CONCLUSION: The present study demonstrated increased oxidative stress, reduced antioxidant defence system in patients with nutritional rachitism, with reduced oxidative stress and a pronounced improvement in the antioxidant system with vitamin D treatment.

Maternal vitamin D status: implications for the development of infantile nutritional rickets.

The mother is the major source of circulating 25-hydroxyvitamin D concentration in the young infant. Maternal vitamin D status is an important factor in determining the vitamin D status of the infant and their risk of developing vitamin D deficiency and infantile nutritional rickets. There is evidence that the current supplementation recommendations, particularly for pregnant and lactating women, are inadequate to ensure vitamin D sufficiency in these groups. A widespread and concerted effort is needed to ensure daily supplementation of breastfed and other infants at high risk with vitamin D 400 IU from birth and of pregnant women in high-risk communities with 2000 IU. Future studies are required to determine the optimal doses of vitamin D supplementation in pregnancy and during lactation, and for normalizing vitamin D stores in infancy to reduce the prevalence of infantile nutritional rickets. Operational research studies are needed to understand the best methods of implementing supplementation programs and the factors that are likely to impede their success.

Low vitamin D status: definition, prevalence, consequences, and correction.

Vitamin D is obtained from cutaneous production when 7-dehydrocholesterol is converted to vitamin D(3) (cholecalciferol) by ultraviolet B radiation or by oral intake of vitamin D(2) (ergocalciferol) and D(3). An individual's vitamin D status is best evaluated by measuring the circulating 25-hydroxyvitamin D (25(OH)D) concentration. Although controversy surrounds the definition of low vitamin D status, there is increasing agreement that the optimal circulating 25(OH)D level should be approximately 30 to 32 ng/mL or above. Using this definition, it has been estimated that approximately three-quarters of all adults in the United States have low levels. Low vitamin D status classically has skeletal consequences such as osteomalacia/rickets. More recently, associations between low vitamin D status and increased risk for various nonskeletal morbidities have been recognized; whether all of these associations are causally related to low vitamin D status remains to be determined. To achieve optimal vitamin D status, daily intakes of at least 1000 IU or more of vitamin D are required. The risk of toxicity with "high" amounts of vitamin D intake is low. Substantial between-individual variability exists in response to the same administered vitamin D dose. When to monitor 25(OH)D levels has received little attention. Supplementation with vitamin D(3) may be preferable to vitamin D(2).

Rickets in the Benelux. A case report of two Indian immigrants.

The last decades showed a resurgence of rickets and osteomalacia in the developed countries. In this report, we present two cases of dietary rickets in Indian teenage brothers who migrated to Europe. Supplementation of calcium and vitamin D3 to their diet resulted in rapid relief of musculoskeletal symptoms.

Rickets in lion cubs at the London Zoo in 1889: some new insights.

In 1889, when Dr John Bland-Sutton, a prominent surgeon in London, England, was consulted concerning fatal rickets in more than 20 successive litters of lion cubs at the London Zoo, he evaluated the role of diet relative to the development of rickets. He prescribed goat meat and bones and cod-liver oil to be added to the lean horse-meat diet of the cubs and their mothers. Rickets reversed, the cubs survived, and litters were reared successfully. In classic controlled studies conducted in puppies and young rats 3 decades later, the crucial role of calcium, phosphate, and vitamin D in both prevention and therapy of rickets was elucidated. Later studies led to the identification of the structural features of vitamin D. Although the Bland-Sutton interventional diet obviously provides calcium and phosphate from bones and vitamin D from cod-liver oil, other benefits of this diet were not initially recognized. Chewing bones promotes tooth and gum health and removes bacteria-laden tartar. Cod-liver oil also contains vitamin A, which is essential for the prevention of infection and for epithelial cell health. Taurine-conjugated bile salts are also necessary for the intestinal absorption of fat-soluble vitamins, including A and D. Moreover, unlike dogs and rats, all feline species are unable to synthesize taurine yet can only conjugate bile acids with taurine. This sulfur-containing beta-amino acid must be provided in the carnivorous diet of a large cat. Taurine-conjugated bile salts were provided in the oil cold-pressed from cod liver. The now famous Bland-Sutton "experiment of nature," namely, fatal rickets in lion cubs, was cured by the addition of minerals and vitamin D. However, gum health and the presence of taurine-conjugated bile salts undoubtedly permitted absorption of vitamin A and D, the latter promoting the cure of rickets.

Nuevas recomendaciones diarias de ingesta de calcio y vitamina D: prevención del raquitismo nutricional / New recommendations for the daily intake of calcium and vitamin D: prevention of nutritional rickets

El raquitismo atribuible al déficit de vitamina D, tanto en su forma clínica como subclínica, se sigue detectando en todo el mundo. En este artículo se han revisado las nuevas guías de la National Academy of Sciences (NAS), que recomiendan una ingesta mínima de 200 UI diarias de vitamina D para prevenirlos signos clínicos y analíticos de deficiencia de vitamina D, tanto en lactantes como en la infancia y adolescencia. En función de estas recomendaciones, la Academia Americana de Pediatría (AAP) aconseja la ingesta de alimentos ricos en calcio y vitamina D y la suplementación con esta vitamina en los caso sen que no se asegura una ingesta mínima de 200 UI o una exposición solar adecuada(AU)

Clinical and subclinical rickets attributable to vitamin D deficiency is still reported all over the world. In this article, the new guidelines of the National Academy of Sciences have been reviewed and an intake of at least 200 IU per day of vitamin D is recommended to prevent clinical and laboratory findings secondary to vitamin D-deficiency rickets in infants, children and adolescents. Because of these recommendations, the American Academy of Pediatrics recommends the consumption of foods with a high content of calcium and vitamin D and supplementation with this vitamin in children without a minimum intake of 200 IU per day or in the absence of adequate exposure to sunlight(AU)