High-dose Vitamin Supplements Research Articles

Current Diagnosis and Management of Abetalipoproteinemia.

Abetalipoproteinemia (ABL) is a rare autosomal recessive disorder caused by biallelic pathogenic mutations in the MTTP gene. Deficiency of microsomal triglyceride transfer protein (MTTP) abrogates the assembly of apolipoprotein (apo) B-containing lipoprotein in the intestine and liver, resulting in malabsorption of fat and fat-soluble vitamins and severe hypolipidemia. Patients with ABL typically manifest steatorrhea, vomiting, and failure to thrive in infancy. The deficiency of fat-soluble vitamins progressively develops into a variety of symptoms later in life, including hematological (acanthocytosis, anemia, bleeding tendency, etc.), neuromuscular (spinocerebellar ataxia, peripheral neuropathy, myopathy, etc.), and ophthalmological symptoms (e.g., retinitis pigmentosa). If left untreated, the disease can be debilitating and even lethal by the third decade of life due to the development of severe complications, such as blindness, neuromyopathy, and respiratory failure. High dose vitamin supplementation is the mainstay for treatment and may prevent, delay, or alleviate the complications and improve the prognosis, enabling some patients to live to the eighth decade of life. However, it cannot fully prevent or restore impaired function. Novel therapeutic modalities that improve quality of life and prognosis are awaited. The aim of this review is to 1) summarize the pathogenesis, clinical signs and symptoms, diagnosis, and management of ABL, and 2) propose diagnostic criteria that define eligibility to receive financial support from the Japanese government for patients with ABL as a rare and intractable disease. In addition, our diagnostic criteria and the entry criterion of low-density lipoprotein cholesterol (LDL-C) ＜15 mg/dL and apoB ＜15 mg/dL can be useful in universal or opportunistic screening for the disease. Registry research on ABL is currently ongoing to better understand the disease burden and unmet needs of this life-threatening disease with few therapeutic options.

New Classification and Management of Abetalipoproteinemia and Related Disorders

New Classification and Management of Abetalipoproteinemia and Related Disorders

The Long History of Vitamin C: From Prevention of the Common Cold to Potential Aid in the Treatment of COVID-19.

From Pauling’s theories to the present, considerable understanding has been acquired of both the physiological role of vitamin C and of the impact of vitamin C supplementation on the health. Although it is well known that a balanced diet which satisfies the daily intake of vitamin C positively affects the immune system and reduces susceptibility to infections, available data do not support the theory that oral vitamin C supplements boost immunity. No current clinical recommendations support the possibility of significantly decreasing the risk of respiratory infections by using high-dose supplements of vitamin C in a well-nourished general population. Only in restricted subgroups (e.g., athletes or the military) and in subjects with a low plasma vitamin C concentration a supplementation may be justified. Furthermore, in categories at high risk of infection (i.e., the obese, diabetics, the elderly, etc.), a vitamin C supplementation can modulate inflammation, with potential positive effects on immune response to infections. The impact of an extra oral intake of vitamin C on the duration of a cold and the prevention or treatment of pneumonia is still questioned, while, based on critical illness studies, vitamin C infusion has recently been hypothesized as a treatment for COVID-19 hospitalized patients. In this review, we focused on the effects of vitamin C on immune function, summarizing the most relevant studies from the prevention and treatment of common respiratory diseases to the use of vitamin C in critical illness conditions, with the aim of clarifying its potential application during an acute SARS-CoV2 infection.

The effects of high doses of vitamin D on the composition of the gut microbiome of adolescent girls

Animal studies suggest that vitamin D can change the gut microbiome. The primary aim of this study was to evaluate the effect of a high dose supplementation of vitamin D on the composition of the gut microbiome. After DNA extraction, TaqMan assays were used for the quantitation of selected microbiome in the feces of 50 adolescent girls before and after vitamin D supplementation. The expression fold changes for Enterococcus, Bifidobacterium, Lactobacillus, Bacteroidetes and Firmicutes were; 1.05, 1.20, 0.76, 0.28 and 1.50 respectively. Bacteroidetes and Lactobacillus fell by 72% (P<0.0001) and 24% (P=0.006) respectively, whilst Firmicutes and Bifidobacterium were increased by 1.5 (P<0.0001), 1.2 (P<0.0001) fold after supplementation. Our results suggested that a high dose supplementation of vitamin D alter the human gut microbiome composition. Future studies are required for a better understanding of the mechanisms by which vitamin D affects the gut microbiome.

High Dose Supplementation of Vitamin D Affects Measures of Systemic Inflammation: Reductions in High Sensitivity C-Reactive Protein Level and Neutrophil to Lymphocyte Ratio (NLR) Distribution.

The prevalence of Vitamin D deficiency is increasing worldwide, which has be shown to be associated with increased risk of cardiovascular disease (CVD), autoimmune disease, and metabolic syndrome. These conditions are also associated with a heightened state of inflammation. The aim of the current study was to evaluate the effect of vitamin D supplementation on serum C-Reactive Protein (CRP) level and Neutrophil-to-lymphocyte ratio (NLR) distribution in a large cohort of adolescent girls. A total of 580 adolescent girls were recruited follow by evaluation of CRP and hematological parameters before and after supplementation with vitamin D supplements as 9 of 50000 IU cholecalciferol capsules for 9 weeks taken at weekly intervals. At baseline, serum hs-CRP level was 0.9 (95%CI: 0.5-1.8), while this value after intervention was reduced to 0.8 (95%CI: 0.3-1.6; P = 0.007). Similar results were also detected for NLR (e.g., NLR level was 1.66 ± 0.72 and 1.53 ± 0.67, P = 0.002, before and after therapy with compliance rate of >95.2%). Moreover, we found an association between hs-CRP and BMI, triglyceride, white blood cell count, and lymphocytes. Interestingly we observed a significant reduction in neutrophil count and CRP level after high dose vitamin D supplementation. Our findings showed that the high dose supplementation of vitamin D affects measures of systemic inflammation: reductions in High Sensitivity C-Reactive Protein level and Neutrophil-to-lymphocyte ratio (NLR) distribution. J. Cell. Biochem. 118: 4317-4322, 2017. © 2017 Wiley Periodicals, Inc.

Vitamin C in the Prevention and Treatment of the Common Cold.

During the winter months, absenteeism or decreased productivity at work or school can often be attributed to symptoms of the common cold. Many people seek over-the-counter (OTC) products for their symptoms, and some of the commonly purchased products are those with high-dose supplements of vitamin C (ascorbic acid). The common cold causes enormous morbidity worldwide, and it is important to know the effects of vitamin C for both preventive and therapeutic purposes to correctly recommend the proper OTC product for these symptoms. The purpose of this article is to review the current data on the relationship between vitamin C and immune function, specifically, the utility of vitamin C supplementation in the prevention and treatment of the common cold.

EDTA Chelation Therapy to Reduce Cardiovascular Events in Persons with Diabetes.

The Trial to Assess Chelation Therapy (TACT) was a randomized double-blind placebo-controlled trial enrolling patients age ≥50 years with prior myocardial infarction. TACT used a 2 × 2 factorial design to study ethylene diamine tetraacetic acid (EDTA) chelation and high-dose vitamin supplementation. Chelation provided a modest but significant reduction in cardiovascular endpoints. The benefit was stronger and significant among participants with diabetes but absent in those without diabetes. Mechanisms by which chelation might reduce cardiovascular risk in persons with diabetes include the effects of EDTA chelation on transition and toxic metals. Transition metals, particularly copper and iron, play important roles in oxidative stress pathways. Toxic metals, in particular cadmium and lead, are toxic for the cardiovascular system. This review discusses the epidemiologic evidence and animal and human studies supporting the role of these metals in the development of diabetes and ischemic heart disease and potential ways by which EDTA chelation could confer cardiovascular benefit.

No evidence supports vitamin E indiscriminate supplementation

For many years, the prevailing concept was that LDL oxidation plays the central role in atherogenesis. As a consequence, supplementation of antioxidants, particularly vitamin E, became very popular. Unfortunately, major randomized clinical trials yielded disappointing results and recent meta-analyses concluded that indiscriminate, high dose vitamin E supplementation results in increased mortality. This conclusion raised (quite reasonable) criticism, much of which referred to the characteristics of meta-analysis. In our recent study, we used a Markov-model approach, which is free of most of the limitations of meta-analyses. Our major finding was that the average quality-adjusted life years (QALY) of vitamin E- supplemented individuals was 0.30 QALY (95%CI 0.21 to 0.39) less than that of untreated people. In our view, this supports the view that indiscriminate supplementation of high dose vitamin E can not be recommended to the general public.In the present communication we address several recent studies that demonstrated negative effects of vitamin E and raise possible mechanisms that may be responsible for the harmful effects of vitamin E supplementation. We also review recent studies conducted with specific groups of patients that gained from vitamin E supplementation, indicating that although, on the average, indiscriminate supplementation of high dose vitamin E is not beneficial, specific populations may gain from vitamin E. The challenge is to establish selection criteria that will predict who is likely to benefit from vitamin E supplementation. Such criteria may be based either on the assumption that antioxidants are likely to be beneficial for people under oxidative stress or on knowledge regarding the benefit of sick people with certain diseases. In short, we adopt the view that vitamin E is a "double-edge sword" that should not be consumed until criteria are defined to predict who is likely to benefit from high dose supplementation of vitamin E.

High-dose vitamin supplements for cigarette smokers: caution is indicated.

Results from human intervention studies indicate that smokers should avoid using high-dose dietary beta-carotene supplements. In addition, problems may exist for smokers with high-dose vitamin E supplements.

Assessing Toxicity in Cancer Chemoprevention Trials: The Other Side of the Coin

Clinical cancer chemoprevention started by studying natural agents presumed to be virtually free of toxicity. Beginning with these agents, however, the history of the major cancer chemoprevention trials has shown that evaluating adverse effects is every bit as important as evaluating preventive

Treatment of nonexudative (dry) age-related macular degeneration

The purpose of this report is to review the recent literature and summarize currently available and potential new treatment options for nonexudative age-related macular degeneration. High-dose vitamin supplementation may have some associated systemic toxicity. It is important to check that the patient is taking beta-carotene and not vitamin A as retinal acetate or palmitate, which have been associated with osteoporosis and hepatotoxicity. High-dose vitamins E and C may be associated with cardiovascular disease. Decreasing inflammation by lowering systemic cardiac C-reactive protein, fibrinogen and cholesterol may be important, especially in light of recent epidemiologic and genetic data. The results of randomized trials of laser treatment for drusen and rheopheresis should be available during 2006. Treatment with these modalities before the results of the trials are evaluated should be avoided. The holy grail of therapy for age-related macular degeneration is to avoid the development of choroidal neovascularization. High-dose vitamin supplementation should be used only in those in whom it is indicated and inflammatory parameters including highly sensitive C-reactive protein, fibrinogen and cholesterol should be stabilized because there are data associating these parameters with age-related macular degeneration and also with cardiovascular disease.

Opposite effects of low and high dose supplementation of vitamin E on survival of MRL/ lpr mice

Objective The purpose of this study is to investigate the effects of vitamin E supplementation on the autoimmune disease course in MRL/ lymphoproliferative mice. Methods Three-month-old MRL/lymphoproliferative lpr female mice were fed an AIN-76 diet containing 50 mg/kg (control), 250 mg/kg (E5), 375 mg/kg (E7.5), or 500 mg/kg (E10) all-rac-α-tocopheryl acetate. Eight mice per group were killed for analysis after two months of experimental diets, and the rest of the mice were followed up to observe their proteinuria levels and life span. Results The data suggest that the life span of the E5 group was longer than the E10 group. Though α-tocopherol content in the plasma, liver, and kidneys increased in the mice fed the diet supplemented with vitamin E, the thiobarbituric acid reactive substance values in the liver and kidneys among these groups were not significantly different. IgM anti-ds-DNA and anticardiolipin antibodies were significantly higher in the E10 group than in those of the other groups. Phytohemagglutinin-stimulated interleukin (IL)-2 secretion was significantly lower, but concanavalinA-stimulated IL-4 and IL-10 production was significantly higher in the E10 group compared with the control group. The in vitro study also showed decreased IL-2 secretion and messenger RNA expression in phytohemagglutinin-stimulated splenocytes cultured in medium supplemented with high doses of vitamin E, but increased IL-2 with low doses of vitamin E. Conclusions Our data suggest that low and high dose supplementation of vitamin E has the opposite effect on the survival of MRL/ lpr mice. The inhibitory effect of Th1 from high vitamin E content may not be beneficial for those suffering from Th2 prone autoimmune diseases, such as systemic lupus erythematosus.

A Pilot Study of Vitamins to Lower Plasma Homocysteine Levels in Alzheimer Disease

OBJECTIVE Authors determined the impact of high-dose vitamin supplements on plasma homocysteine levels in patients with Alzheimer disease (AD). METHODS Authors used an open-label trial of folic acid, vitamin B12, and vitamin B6, in combination for 8 weeks, with measurement of plasma homocysteine levels in the fasting state and after methionine-loading. A total of 69 subjects with AD were enrolled, including 33 who were taking standard multivitamin supplements; 66 were available at 8-week follow-up. RESULTS The high-dose vitamin regimen was associated with a significant reduction in fasting and post–methionine-loading homocysteine. Reductions were greater in the subgroup not using multivitamins, but were also significant in the multivitamin users. CONCLUSION High-dose vitamin supplementation reduces homocysteine levels in patients with AD. The effect of supplementation on rate of cognitive decline will be assessed later in a randomized, double-blind study. Authors determined the impact of high-dose vitamin supplements on plasma homocysteine levels in patients with Alzheimer disease (AD). Authors used an open-label trial of folic acid, vitamin B12, and vitamin B6, in combination for 8 weeks, with measurement of plasma homocysteine levels in the fasting state and after methionine-loading. A total of 69 subjects with AD were enrolled, including 33 who were taking standard multivitamin supplements; 66 were available at 8-week follow-up. The high-dose vitamin regimen was associated with a significant reduction in fasting and post–methionine-loading homocysteine. Reductions were greater in the subgroup not using multivitamins, but were also significant in the multivitamin users. High-dose vitamin supplementation reduces homocysteine levels in patients with AD. The effect of supplementation on rate of cognitive decline will be assessed later in a randomized, double-blind study.

A Pilot Study of Vitamins to Lower Plasma Homocysteine Levels in Alzheimer Disease

Authors determined the impact of high-dose vitamin supplements on plasma homocysteine levels in patients with Alzheimer disease (AD). Authors used an open-label trial of folic acid, vitamin B(12), and vitamin B(6), in combination for 8 weeks, with measurement of plasma homocysteine levels in the fasting state and after methionine-loading. A total of 69 subjects with AD were enrolled, including 33 who were taking standard multivitamin supplements; 66 were available at 8-week follow-up. The high-dose vitamin regimen was associated with a significant reduction in fasting and post-methionine-loading homocysteine. Reductions were greater in the subgroup not using multivitamins, but were also significant in the multivitamin users. High-dose vitamin supplementation reduces homocysteine levels in patients with AD. The effect of supplementation on rate of cognitive decline will be assessed later in a randomized, double-blind study.

Immunomodulatory effects of high-dose α-tocopherol acetate on mice subjected to sidestream cigarette smoke

Several recent epidemiological investigations raise serious questions about the health effects of high-dose supplements of Vitamin E (VE) in cigarette smokers. To examine these findings, a total of 96 C57BL/6 mice were randomly assigned to eight groups in a 2×4 factorial design (smoke vs. sham smoke and normal diet vs. 3 VE supplements). The mice were exposed to sidestream cigarette smoke (SSCS), at 0.4 mg total particulate matter/m 3 air, from standard research cigarettes (1R4)/day or filtered room air at 30 min/day, 5 days/week, for 9 weeks through a nose-only exposure chamber. The American Institute of Nutrition 93G purified rodent diet was modulated with 75 (regular diet, 1-fold), 1050 (15-fold), 5550 (75-fold), and 11 175 (150-fold) IU dl-α-tocopherol acetate (α-TA)/kg as VE supplementation and provided ad libitum at an average intake rate of 4.11 g diet/mouse/day. This result demonstrated that SSCS exposure results in lung dysfunction, as indicated by a decrease of pulmonary dynamic compliance ( C dyn) and increase of lung resistance ( R L), and body weight loss in mice fed with regular diet. These changes accompanied with increases of bronchoalveolar lavage (BAL) concentrations of cytokines interleukin (IL)-1β, IL-4 and IFN-γ, as well as hepatic lipid peroxidation. However, supplemental α-TA at the doses of ⩾1050 IU/kg diet prevented the SSCS-induced body weight loss and lung dysfunction. α-TA at ⩾5550 IU/kg significantly increased BAL levels of IL-2 and IL-4 in both the sham SSCS and the SSCS groups. Given at 5550 IU α-TA/kg, but not higher, mice elevated BAL IL-1β level if they were exposed to SSCS. Hepatic lipid peroxidation was decreased in a dose-dependent fashion with different α-TA supplements in both the sham SSCS and SSCS groups. Neither SSCS nor α-TA had an effect on lung permeability, BAL IL-6, splenic T and B lymphocyte proliferation and their T helper (Th)1 and Th2 cytokines measured among all groups. Data suggest that supplemental α-TA may be needed to counteract SSCS-induced oxidative stress, but that potential side effects introduced by high dosage of this synthetic compound should be considered.

The Age-Related Eye Disease Study (AREDS): Design Implications AREDS Report No. 1

The Age-Related Eye Disease Study (AREDS) was initially conceived as a long-term multicenter, prospective study of the clinical course of age-related macular degeneration (AMD) and age-related cataract. Data on progression rates and risk factors from the study will increase understanding of the clinical course of both conditions, generate hypotheses about etiology, and aid in the design of clinical trials of potential interventions. In addition to collecting natural history data, AREDS includes a clinical trial of high-dose vitamin and mineral supplements for AMD and a clinical trial of high-dose vitamin supplements for cataract. The clinical trials were initiated largely because of the widespread public use in the United States of commercially available pharmacologic doses of vitamins and minerals to treat these two eye conditions and the absence of definitive studies on the safety and efficacy of their use. Important design issues for the clinical trials include: defining cataract and AMD, estimating event rates, determining the type and dosage of vitamins and minerals to be tested for each condition, and identifying the parameters necessary for monitoring safety and efficacy. This paper describes the AREDS design, including the study rationale and operational structure, and the approach adopted to combine, for two diseases, clinical trials with a natural history study. Control Clin Trials 1999;20:573–600

Riboflavin responsive multiple acyl-CoA dehydrogenase deficiency: Functional evaluation of recovery after high dose vitamin supplementation

The effect of riboflavin supplementation on muscle performance and exercise metabolism was investigated in four patients with multiple acyl-coenzyme A dehydrogenase deficiency (MAD). Maximum oxygen consumption and endurance measurements were performed to assess the patients' aerobic capacity and energy metabolism during exercise. They were tested before and after treatment with pharmacological doses of riboflavin. The initially low maximum oxygen consumption and high levels of blood lactate during submaximal exercise suggest that the oxidation of both fatty acids and carbohydrates was severely impaired. All four patients experienced a dramatic improvement in aerobic performance under riboflavin supplementation.

Vitamin therapy in the absence of obvious deficiency. What is the evidence?

Vitamins are a group of organic compounds occurring naturally in food and are necessary for good health. Lack of a vitamin may lead to a specific deficiency syndrome, which may be primary (due to inadequate diet) or secondary (due to malabsorption or to increased metabolic need), and it is rational to use high-dose vitamin supplementation in situations where these clinical conditions exist. However, pharmacological doses of vitamins are claimed to be of value in a wide variety of conditions which have no, or only a superficial, resemblance to the classic vitamin deficiency syndromes. The enormous literature on which these claims are based consists mainly of uncontrolled clinical trials or anecdotal reports. Only a few studies have made use of the techniques of randomisation and double-blinding. Evidence from such studies reveals a beneficial therapeutic effect of vitamin E in intermittent claudication and fibrocystic breast disease and of vitamin C in pressure sores, but the use of vitamin A in acne vulgaris, vitamin E in angina pectoris, hyperlipidaemia and enhancement of athletic capacity, of vitamin C in advanced cancer, and niacin in schizophrenia has been rejected. Evidence is conflicting or inconclusive as to the use of vitamin C in the common cold, asthma and enhancement of athletic capacity, of pantothenic acid in osteoarthritis, and folic acid (folacin) in neural tube defects. Most of the vitamins have been reported to cause adverse effects when ingested in excessive doses. It is therefore worthwhile to consider the risk-benefit ratio before embarking upon the use of high-dose vitamin supplementation for disorders were proof of efficacy is lacking.