Research - Vitamin C
Vitamin C – A new player in regulation of the cancer epigenome
Linn Gillberg ab Andreas D.Ørskov ab Minmin Liuc Laurine B.S.Harsløf a Peter A.Jones c Kirsten Grønbæk ab
Over the past few years it has become clear that vitamin C, as a provider of reduced iron, is an essential factor for the function of epigenetic regulators that initiate the demethylation of DNA and histones. Vitamin C deficiency is rare in the general population, but is frequently observed in patients with cancer. Genes encoding epigenetic regulators are often mutated in cancer, underscoring their central roles in carcinogenesis. In hematological cancers, such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), drugs that reverse epigenetic aberrations are now the standard of care. Recent in vitro studies suggest that vitamin C at physiological concentrations, combined with hypomethylating agents may act synergistically to cause DNA demethylation through active and passive mechanisms, respectively. Additionally, several recent studies have renewed interest in the use of pharmacological doses of vitamin C injected intravenously to selectively kill tumor cells. This review will focus on the potential of vitamin C to optimize the outcome of epigenetic therapy in cancer patients and alternatively to act as a therapeutic at high doses.
Source : Seminars in Cancer Biology
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Genetic and Dietary Factors Influencing the Progression of Nuclear Cataract
Ekaterina Yonova-Doing, MSc Zoe A. Forkin, BSc Pirro G. Hysi, MD, PhD Katie M. Williams, MPhil, FRCOphth Tim D. Spector, MD, PhD, Clare E. Gilbert, FRCOphth, MD Christopher J. Hammond, MD, FRCOphth
To determine the heritability of nuclear cataract progression and to explore prospectively the effect of dietary micronutrients on the progression of nuclear cataract.
Prospective cohort study.
Cross-sectional nuclear cataract and dietary measurements were available for 2054 white female twins from the TwinsUK cohort. Follow-up cataract measurements were available for 324 of the twins (151 monozygotic and 173 dizygotic twins).
MethodsNuclear cataract was measured using a quantitative measure of nuclear density obtained from digital Scheimpflug images. Dietary data were available from EPIC food frequency questionnaires. Heritability was modeled using maximum likelihood structural equation twin modeling. Association between nuclear cataract change and micronutrients was investigated using linear and multinomial regression analysis. The mean interval between baseline and follow-up examination was 9.4 years.
Main Outcome MeasuresNuclear cataract progression.
The best-fitting model estimated that the heritability of nuclear cataract progression was 35% (95% confidence interval [CI], 13–54), and individual environmental factors explained the remaining 65% (95% CI, 46–87) of variance. Dietary vitamin C was protective against both nuclear cataract at baseline and nuclear cataract progression (β = −0.0002, P = 0.01 and β = −0.001, P = 0.03, respectively), whereas manganese and intake of micronutrient supplements were protective against nuclear cataract at baseline only (β = −0.009, P = 0.03 and β = −0.03, P = 0.01, respectively).
Genetic factors explained 35% of the variation in progression of nuclear cataract over a 10-year period. Environmental factors accounted for the remaining variance, and in particular, dietary vitamin C protected against cataract progression assessed approximately 10 years after baseline.
Source : Opthalmology
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Association between Dietary Vitamin C Intake and Risk of Prostate Cancer: A Meta-analysis Involving 103,658 Subjects
Xiao-Yan Bai,1 Xinjian Qu,2 Xiao Jiang,1 Zhaowei Xu,1 Yangyang Yang,1 Qiming Su,2 Miao Wang,1,✉ and Huijian Wu1,2,✉
We attempted to systematically determine the association between dietary intake of vitamin C and risk of prostate cancer. PubMed and Embase were searched to obtain eligible studies published before February 2015. Cohort or case-control studies that reported the relative risk (RR)/odds ratio (OR) estimates with 95% confidence intervals (CIs) for the association between vitamin C intake and prostate cancer risk were included. Eighteen studies regarding dietary vitamin C intake were finally obtained, with a total of 103,658 subjects. The pooled RR of prostate cancer for the highest versus the lowest categories of dietary vitamin C intake was 0.89 (95%CI: 0.83-0.94; p = 0.000) with evidence of a moderate heterogeneity (I2 = 39.4%, p = 0.045). Meta-regression analysis suggested that study design accounted for a major proportion of the heterogeneity. Stratifying the overall study according to study design yielded pooled RRs of 0.92 (95%CI: 0.86-0.99, p = 0.027) among cohort studies and 0.80 (95%CI: 0.71-0.89, p = 0.000) among case-control studies, with no heterogeneity in either subgroup. In the dose-response analysis, an inverse linear relationship between dietary vitamin C intake and prostate cancer risk was established, with a 150 mg/day dietary vitamin C intake conferred RRs of 0.91 (95%CI: 0.84-0.98, p = 0.018) in the overall studies, 0.95 (95%CI: 0.90-0.99, p = 0.039) in cohort studies, and 0.79 (95%CI: 0.69-0.91, p = 0.001) in case-control studies. In conclusion, intake of vitamin C from food was inversely associated with prostate cancer risk in this meta-analysis.
Source : Journal of Cancer
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Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH
Jihye Yun1, Edouard Mullarky1,2, Changyuan Lu3, Kaitlyn N. Bosch1, Adam Kavalier3, Keith Rivera4, Jatin Roper5, Iok In Christine Chio4, Eugenia G. Giannopoulou6,*, Carlo Rago7, Ashlesha Muley1, John M. Asara8, Jihye Paik9,Olivier Elemento6, Zhengming Chen10, Darryl J. Pappin4, Lukas E. Dow1, Nickolas Papadopoulos7,Steven S. Gross3, Lewis C. Cantley1,†
More than half of human colorectal cancers (CRCs) carry either KRAS or BRAF mutations, and are often refractory to approved targeted therapies. We report that cultured CRC cells harboring KRAS or BRAFmutations are selectively killed when exposed to high levels of vitamin C. This effect is due to increased uptake of the oxidized form of vitamin C, dehydroascorbate (DHA), via the GLUT1 glucose transporter. Increased DHA uptake causes oxidative stress as intracellular DHA is reduced to vitamin C, depleting glutathione. Thus, ROS accumulates and inactivates glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Inhibiting GAPDH in highly glycolytic KRAS or BRAF mutant cells leads to an energetic crisis and cell death not seen in KRAS and BRAF wild-type cells. High-dose vitamin C impaired tumor growth in Apc/KrasG12Dmutant mice. These results provide a mechanistic rationale for exploring the therapeutic use of vitamin C for CRCs with KRAS or BRAF mutations.
Source : Scence
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Vitamin and carotenoid intake and risk of head-neck cancer subtypes in the Netherlands Cohort Study1,2
Background: Head and neck cancer (HNC) is the seventh most-common type of cancer worldwide. Evidence regarding the potential protective effect of vitamins and carotenoids on HNC is limited and mostly based on case-control studies.
Objective: We evaluated the association of intake of dietary vitamins C and E (including supplementation) and the most-common carotenoids (α-carotene, β-carotene, lutein plus zeaxanthin, lycopene, and β-cryptoxanthin) and risk of HNC and HNC subtypes in a large prospective study.
Design: The Netherlands Cohort Study included 120,852 participants. For efficiency reasons, a case-cohort design was used. At baseline in 1986, participants completed a food-frequency questionnaire. A subcohort was randomly selected from the total cohort. After 20.3 y of follow-up, 3898 subcohort members and 415 HNC cases [131 oral cavity cancer (OCCs), 88 oro-/hypopharyngeal cancer (OHPs), and 193 laryngeal cancer cases] were available for analysis. Rate ratios and 95% CIs for highest (quartile 4) compared with lowest (quartile 1) quartiles of vitamin and carotenoid intake were estimated by using the Cox proportional hazards model.
Results: A strong inverse association was shown between vitamin C and HNC overall (multivariable-adjusted rate ratio for quartile 4 compared with quartile 1: 0.39; 95% CI: 0.23, 0.66; P-trend < 0.001), OCC (multivariable-adjusted rate ratio for quartile 4 compared with quartile 1: 0.35; 95% CI: 0.16, 0.77; P-trend < 0.05), and OHPC (multivariable-adjusted rate ratio for quartile 4 compared with quartile 1: 0.29; 95% CI: 0.12, 0.67; P-trend < 0.01). No statistically significant results were shown for vitamin E, α-carotene, β-carotene, lycopene, and lutein plus zeaxanthin. The association of vitamin E and HNC was modified by alcohol status (P-interaction = 0.003) with lower risks in alcohol abstainers.
Conclusions: With this study, we show an inverse association between intake of vitamin C and the incidence of HNC and HNC-subtypes. Future research is recommended to investigate the underlying mechanisms and to confirm our results, which may be promising for the prevention of HNC.
Source : American Journal of Clinical Nutrition
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Low vitamin C values are linked with decreased physical performance and increased oxidative stress: reversal by vitamin C supplementation
- Vassilis Paschalis,
- Anastasios A. Theodorou,
- Antonios Kyparos,
- Konstantina Dipla,
- Andreas Zafeiridis,
- George Panayiotou,
- Ioannis S. Vrabas,
- Michalis G. Nikolaidis
It has been suggested that part of the failure of antioxidant supplementation to reduce oxidative stress and promote health is that it has been administered in humans with normal levels of antioxidants.
To test this hypothesis, we screened 100 males for vitamin C baseline values in blood. Subsequently, the 10 individuals with the lowest and the 10 with the highest vitamin C values were assigned in two groups. Using a placebo-controlled crossover design, the 20 selected subjects performed aerobic exercise to exhaustion (oxidant stimulus) before and after vitamin C supplementation for 30 days.
The low vitamin C group had lower VO2max values than the high vitamin C group. Vitamin C supplementation in this group marginally increased VO2max. Baseline concentration of F2-isoprostanes and protein carbonyls was higher in the low vitamin C group compared to the high vitamin C group. Vitamin C supplementation decreased the baseline concentration of F2-isoprostanes and protein carbonyls in both groups, yet the decrease was greater in the low vitamin C group. Before vitamin C supplementation, F2-isoprostanes and protein carbonyls were increased to a greater extent after exercise in the high vitamin C group compared to the low vitamin C group. Interestingly, after vitamin C supplementation, this difference was narrowed.
We show for the first time that low vitamin C concentration is linked with decreased physical performance and increased oxidative stress and that vitamin C supplementation decreases oxidative stress and might increase exercise performance only in those with low initial concentration of vitamin C.
Source : EU Journal of Nutrition
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Effect of high dose vitamin C on Epstein-Barr viral infection
Nina A. MikirovaA,C,D,E and Ronald HunninghakeA
Many natural compounds were tested for the ability to suppress viral replication. The present manuscript details an analysis of high dose vitamin C therapy on patients with EBV infection.
The data were obtained from the patient history database at the Riordan Clinic. Among people in our database who were treated with intravenous vitamin C (7.5 g to 50 g infusions) between 1997 and 2006, 178 patients showed elevated levels of EBV EA IgG (range 25 to 211 AU) and 40 showed elevated levels of EBV VCA IgM (range 25 to 140 AU). Most of these patients had a diagnosis of chronic fatigue syndrome, with the rest being diagnosed as having mononucleosis, fatigue, or EBV infection.
Our data provide evidence that high dose intravenous vitamin C therapy has a positive effect on disease duration and reduction of viral antibody levels.
Plasma levels of ascorbic acid and vitamin D were correlated with levels of antibodies to EBV. We found an inverse correlation between EBV VCA IgM and vitamin C in plasma in patients with mononucleosis and CFS meaning that patients with high levels of vitamin C tended to have lower levels of antigens in the acute state of disease.
In addition, a relation was found between vitamin D levels and EBV EA IgG with lower levels of EBV early antigen IgG for higher levels of vitamin D.
The clinical study of ascorbic acid and EBV infection showed the reduction in EBV EA IgG and EBV VCA IgM antibody levels over time during IVC therapy that is consistent with observations from the literature that millimolar levels of ascorbate hinder viral infection and replication in vitro.
Source : Medical Science Monitor
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Additive Antinociceptive Effects of a Combination of Vitamin C and Vitamin E after Peripheral Nerve Injury
- Ruirui Lu,
- Wiebke Kallenborn-Gerhardt,
- Gerd Geisslinger,
- Achim Schmidtko
Accumulating evidence indicates that increased generation of reactive oxygen species (ROS) contributes to the development of exaggerated pain hypersensitivity during persistent pain. In the present study, we investigated the antinociceptive efficacy of the antioxidants vitamin C and vitamin E in mouse models of inflammatory and neuropathic pain. We show that systemic administration of a combination of vitamins C and E inhibited the early behavioral responses to formalin injection and the neuropathic pain behavior after peripheral nerve injury, but not the inflammatory pain behavior induced by Complete Freund's Adjuvant. In contrast, vitamin C or vitamin E given alone failed to affect the nociceptive behavior in all tested models. The attenuated neuropathic pain behavior induced by the vitamin C and E combination was paralleled by a reduced p38 phosphorylation in the spinal cord and in dorsal root ganglia, and was also observed after intrathecal injection of the vitamins. Moreover, the vitamin C and E combination ameliorated the allodynia induced by an intrathecally delivered ROS donor. Our results suggest that administration of vitamins C and E in combination may exert synergistic antinociceptive effects, and further indicate that ROS essentially contribute to nociceptive processing in special pain states.
Source : PLOSone
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Antioxidants prevent memory deficits provoked by chronic variable stress in rats.
Tagliari B1, Scherer EB, Machado FR, Ferreira AG, Dalmaz C, Wyse AT.Author information
Learning and memory deficits occur in depression and other stress related disorders. Although the pathogenesis of cognitive impairment after stress has not been fully elucidated, factors such as oxidative stress and neurotrophins are thought to play possible roles. Here we investigated the effect of treatment with vitamin E (40 mg/kg) and vitamin C (100 mg/kg) on the effects elicited by chronic variable stress on rat performance in Morris water maze. Brain-derived neurotrophic factor (BDNF) immunocontent was also evaluated in hippocampus of rats. Sixty-day old Wistar rats were submitted to different stressors for 40 days (stressed group). Half of stressed group received administration of vitamins once a day, during the period of stress. Chronically stressed rats presented a marked decrease in reference memory in the water maze task as well as a reduced efficiency to find the platform in the working memory task. Rats treated with vitamins E and C had part of the above effects prevented, suggesting the participation of oxidative stress in such effects. The BDNF levels were not altered in hippocampus of stressed group when compared to controls. Our findings lend support to a novel therapeutic strategy, associated with these vitamins, to the cognitive dysfunction observed in depression and other stress related diseases.
Source : Neurochem Res
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Dietary nutrient intakes and skin-aging appearance among middle-aged American women1,2,3,4
Background: Nutritional factors play a key role in normal dermatologic functioning. However, little is known about the effects of diet on skin-aging appearance.
Objective: We evaluated the associations between nutrient intakes and skin-aging appearance.
Design: Using data from the first National Health and Nutrition Examination Survey, we examined associations between nutrient intakes and skin aging in 4025 women (40–74 y). Nutrients were estimated from a 24-h recall. Clinical examinations of the skin were conducted by dermatologists. Skin-aging appearance was defined as having a wrinkled appearance, senile dryness, and skin atrophy.
Results: Higher vitamin C intakes were associated with a lower likelihood of a wrinkled appearance [odds ratio (OR) 0.89; 95% CI: 0.82, 0.96] and senile dryness (OR: 0.93; 95% CI: 0.87, 0.99). Higher linoleic acid intakes were associated with a lower likelihood of senile dryness (OR: 0.75; 95% CI: 0.64, 0.88) and skin atrophy (OR: 0.78; 95% CI 0.65, 0.95). A 17-g increase in fat and a 50-g increase in carbohydrate intakes increased the likelihood of a wrinkled appearance (OR: 1.28 and 1.36, respectively) and skin atrophy (OR: 1.37 and 1.33, respectively). These associations were independent of age, race, education, sunlight exposure, income, menopausal status, body mass index, supplement use, physical activity, and energy intake.
Conclusions: Higher intakes of vitamin C and linoleic acid and lower intakes of fats and carbohydrates are associated with better skin-aging appearance. Promoting healthy dietary behaviors may have additional benefit for skin appearance in addition to other health outcomes in the population.
Source : American Journal Clinical Nutrition
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Vitamin C linked to Reduced Stroke Risk
A study due to be presented at a conference later this year suggests that eating foods containing vitamin C, such as oranges, peppers, strawberries, papaya and broccoli, may be linked to a reduced risk for hemorrhagic stroke.
According to the US Centers for Disease Control and Prevention (CDC), stroke is the fourth leading cause of death in the US, where every year 795,000 Americans suffer a stroke and 130,000 die from one.
There are two main types of stroke: ischemic and hemorrhagic. Ischemic stroke, by far the most common type, is where a blockage in a blood vessel stops blood from getting to one or more parts of the brain. Hemorrhagic stroke is much rarer but more deadly and occurs when a weakened blood vessel in the brain ruptures and allows blood to leak into and around the brain.
Study author Dr. Stéphane Vannier, of Pontchaillou University Hospital in Rennes, France, says:
"Our results show that vitamin C deficiency should be considered a risk factor for this severe type of stroke, as were high blood pressure, drinking alcohol and being overweight in our study."
The study compared 65 patients who had experienced a hemorrhagic stroke with 65 healthy counterparts.
Both groups underwent blood tests that checked their vitamic C levels. The results showed that 41% of all participants had normal levels, 45% had depleted levels, and 14% had levels so low they were considered deficient in vitamin C.
Participants who experienced stroke had depleted levels of vitamin C However, on average, the participants who had experienced a stroke had depleted levels, while the ones who had not had a stroke had normal levels of vitamin C in their blood.
The results have not been published in a peer-reviewed journal. The American Academy of Neurology released these details to the media in advance of its 66th Annual Meeting, due to take place in Philadelphia, PA, at the end of April, when fuller details of the study will be presented.
Dr. Vannier says more research is now needed to confirm the findings and find out how vitamin C works to reduce stroke risk.
He suggests one way vitamin C might reduce stroke risk could be by reducing blood pressure, and he adds that vitamin C has other benefits, like helping to make collagen, a protein that gives structure to skin, bones and tissue.
Source : Medical News Today
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Intravenous Vitamin C May Boost Chemo's Cancer-Fighting Power
Large doses of intravenous vitamin C have the potential to boost chemotherapy's ability to kill cancer cells, according to new laboratory research involving human cells and mice. Vitamin C delivered directly to human and mouse ovarian cancer cells helped kill off those cells while leaving normal cells unharmed, University of Kansas researchers report.
"In cell tissue and animal models of cancer, we saw when you add IV vitamin C it seems to augment the killing effect of chemotherapy drugs on cancer cells," said study co-author Dr. Jeanne Drisko, director of integrative medicine at the University of Kansas Medical Center.
In follow-up human trials, a handful of cervical cancer patients given intravenous vitamin C along with their chemotherapy reported fewer toxic side effects from their cancer treatment, according to the study published in the Feb. 5 issue of Science Translational Medicine.
"In those patients, we didn't see any ill effects and we noticed they had fewer effects from the chemotherapy," Drisko said. "It seemed to be protecting the healthy cells while killing the cancer cells."
Intravenous vitamin C has been considered an integrative medical therapy for cancer since the 1970s, Drisko noted.
But vitamin C's cancer-killing potential hasn't been taken seriously by mainstream medicine ever since clinical trials performed by the Mayo Clinic with oral vitamin C in the late 1970s and early 1980s found no anti-cancer effects, she explained.
Researchers have since argued that those trials were flawed because vitamin C taken orally is absorbed by the gut and excreted by the kidneys before its levels can build up in the bloodstream.
But it's been hard to attract funding for further research. There's no reason for pharmaceutical companies to fund vitamin C research, and federal officials have been uninterested in plowing research dollars into the effort since the Mayo research was published, Drisko said.
This latest investigation began with researchers exposing human ovarian cancer cells to vitamin C in the lab. They found that the cells suffered DNA damage and died off, while normal cells were left unharmed.
The researchers then tested vitamin C on mice with induced ovarian cancer. The vitamin appeared to help chemotherapy drugs either inhibit the growth of tumors or help shrink them.
Finally, the team conducted a pilot phase clinical trial involving 27 patients with stage III or stage IV ovarian cancer.
The patients who received intravenous vitamin C along with their chemotherapy reported less toxicity of the brain, bone marrow and major organs, the investigators found.
These patients also appeared to add nearly 8.75 months to the time before their disease relapsed and progressed, compared with people who only received chemotherapy. The researchers did note that the study was not designed to test the statistical significance of that finding.
Vitamin C in the bloodstream helps kill cancer cells because it chemically converts into hydrogen peroxide when it interacts with tumors, Drisko said.
"If you can get your blood levels of vitamin C very high, it gets driven into the space around the cancer cells," she explained. "In that space, it's converted into hydrogen peroxide. It's very similar to what our white blood cells do. They create hydrogen peroxide to fight infection."
Dr. Stephanie Bernik, chief of surgical oncology at Lenox Hill Hospital in New York City, said intravenous vitamin C therapy is not unheard of among cancer doctors.
"I've had patients come in and say they were doing vitamin C intravenous therapy," Bernik said. "I always tell them we don't know enough to know whether it is good or bad."
This new research raises interesting possibilities, but until larger clinical trials are conducted Bernik says her advice to patients will not change.
"You have to do a bigger study with patients and look at outcomes. You also have to make sure these treatments don't interfere with the treatments we're giving currently," she said. "There may be some efficacy in what they're doing. It just needs to be proven. This is just the start of more studies looking at this in-depth."
Dr. Michael Seiden, chief medical officer for The US Oncology Network, agreed.
"It is important to emphasize that many vitamin therapies have shown interesting results when applied to cancer cells in test tubes yet, to date, these approaches typically are not effective and occasionally prove harmful in human studies," he said. "At this time, there is still no evidence that high-dose vitamin C should be part of the treatment for women with ovarian cancer."
While she agreed that larger trials need to be conducted, Drisko was not as hesitant.
"It's safe. It's inexpensive. There's a plausible mechanism we're investigating for why it works," she said. "We should be using this in patients, rather than dragging our feet and worrying about using it at all."
SOURCES: Jeanne Drisko, M.D., endowed professor and director, integrative medicine, University of Kansas Medical Center, Kansas City; Stephanie Bernik, M.D., chief, surgical oncology, Lenox Hill Hospital, New York City; Michael Seiden, M.D., chief medical officer, The US Oncology Network; Feb. 5, 2014, Science Translational Medicine
Source : Medline
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Association of vitamin E and C supplement use with cognitive function and dementia in elderly men
- K.H. Masaki, MD,
- K.G. Losonczy, MA,
- G. Izmirlian, PhD,
- D.J. Foley, MS,
- G.W. Ross, MD,
- H. Petrovitch, MD,
- R. Havlik, MD and
- L.R. White, MD
Objective: To determine whether use of vitamin E and C supplements protects against subsequent development of dementia and poor cognitive functioning.
Methods: The Honolulu–Asia Aging Study is a longitudinal study of Japanese-American men living in Hawaii. Data for this study were obtained from a subsample of the cohort interviewed in 1982, and from the entire cohort from a mailed questionnaire in 1988 and the dementia prevalence survey in 1991 to 1993. The subjects included 3,385 men, age 71 to 93 years, whose use of vitamin E and C supplements had been ascertained previously. Cognitive performance was assessed with the Cognitive Abilities Screening Instrument, and subjects were stratified into four groups: low, low normal, mid normal, and high normal. For the dementia analyses, subjects were divided into five mutually exclusive groups: AD (n = 47), vascular dementia (n = 35), mixed/other types of dementia (n = 50), low cognitive test scorers without diagnosed dementia (n = 254), and cognitively intact (n = 2,999; reference).
Results: In a multivariate model controlling for other factors, a significant protective effect was found for vascular dementia in men who had reported taking both vitamin E and C supplements in 1988 (odds ratio [OR], 0.12; 95% CI, 0.02 to 0.88). They were also protected against mixed/other dementia (OR, 0.31; 95% CI, 0.11 to 0.89). No protective effect was found for Alzheimer’s dementia (OR, 1.81; 95% CI, 0.91 to 3.62). Among those without dementia, use of either vitamin E or C supplements alone in 1988 was associated significantly with better cognitive test performance at the 1991 to 1993 examination (OR, 1.25; 95% CI, 1.04 to 1.50), and use of both vitamin E and C together had borderline significance (OR, 1.18; 95% CI, 0.995 to 1.39).
Conclusions: These results suggest that vitamin E and C supplements may protect against vascular dementia and may improve cognitive function in late life.
Source : Journal Neurology
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Vitamin C Prevents Bone Loss in Animal Models
Researchers at Mount Sinai School of Medicine have shown for the first time in an animal model that vitamin C actively protects against osteoporosis, a disease affecting large numbers of elderly women and men in which bones become brittle and can fracture. The findings are published in the October 8 online edition of PLoS ONE. “This study has profound public health implications, and is well worth exploring for its therapeutic potential in people,” said lead researcher Mone Zaidi, MD, Professor of Medicine (Endocrinology, Diabetes and Bone Disease, and of Structural and Chemical Biology, and Director of the Mount Sinai Bone Program.
“The medical world has known for some time that low amounts of vitamin C can cause scurvy and brittle bones, and that higher vitamin C intake is associated with higher bone mass in humans, “said Dr. Zaidi. “What this study shows is that large doses of vitamin C, when ingested orally by mice, actively stimulate bone formation to protect the skeleton. It does this by inducing osteoblasts, or premature bone cells, to differentiate into mature, mineralizing specialty cells.”
The researchers worked with groups of mice whose ovaries had been removed, a procedure known to reduce bone density, and compared them with control mice that had “sham” operations, which left their ovaries intact. The mice with ovariectomies were divided into two groups, one of which was given large doses of vitamin C over eight weeks. The scientists measured the bone mineral density in the lumbar spine, femur, and tibia bones.
The mice who received an ovariectomy – and no vitamin C -- had a much lower bone mineral density (BMD) versus controls, whereas mice who received a ovariectomy and large doses of vitamin C, had roughly the same BMD as the controls, suggesting vitamin C prevented BMD loss in this group.
“Further research may discover that dietary supplements may help prevent osteoporosis in humans,” said Dr. Zaidi. “If so, the findings could be ultimately useful to developing nations where osteoporosis is prevalent and standard medications are sparse and expensive.”
Source : Newswise
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Increase in RDA for Vitamin C Could Help Reduce Heart Disease, Stroke, Cancer
The recommended dietary allowance, or RDA, of vitamin C is less than half what it should be, scientists argue in a recent report, because medical experts insist on evaluating this natural, but critical nutrient in the same way they do pharmaceutical drugs and reach faulty conclusions as a result.The researchers, in Critical Reviews in Food Science and Nutrition, say there’s compelling evidence that the RDA of vitamin C should be raised to 200 milligrams per day for adults, up from its current levels in the United States of 75 milligrams for women and 90 for men.
Rather than just prevent the vitamin C deficiency disease of scurvy, they say, it’s appropriate to seek optimum levels that will saturate cells and tissues, pose no risk, and may have significant effects on public health at almost no expense – about a penny a day if taken as a dietary supplement.
“It’s time to bring some common sense to this issue, look at the totality of the scientific evidence, and go beyond some clinical trials that are inherently flawed,” said Balz Frei, professor and director of the Linus Pauling Institute at Oregon State University, and one of the world’s leading experts on the role of vitamin C in optimum health.
“Significant numbers of people in the U.S. and around the world are deficient in vitamin C, and there’s growing evidence that more of this vitamin could help prevent chronic disease,” Frei said. “The way clinical researchers study micronutrients right now, with the same type of so-called ‘phase three randomized placebo-controlled trials’ used to test pharmaceutical drugs, almost ensures they will find no beneficial effect. We need to get past that.”
Unlike testing the safety or function of a prescription drug, the researchers said, such trials are ill suited to demonstrate the disease prevention capabilities of substances that are already present in the human body and required for normal metabolism. Some benefits of micronutrients in lowering chronic disease risk also show up only after many years or even decades of optimal consumption of vitamin C – a factor often not captured in shorter-term clinical studies.
A wider body of metabolic, pharmacokinetic, laboratory and demographic studies suggests just the opposite, that higher levels of vitamin C could help reduce the chronic diseases that today kill most people in the developed world – heart disease, stroke, cancer, and the underlying issues that lead to them, such as high blood pressure, chronic inflammation, poor immune response and atherosclerosis.
“We believe solid research shows the RDA should be increased,” Frei said. “And the benefit-to-risk ratio is very high. A 200 milligram intake of vitamin C on a daily basis poses absolutely no risk, but there is strong evidence it would provide multiple, substantial health benefits.”
An excellent diet with the recommended five to nine daily servings of fruits and raw or steam-cooked vegetables, together with a six-ounce glass of orange juice, could provide 200 milligrams of vitamin C a day. But most Americans and people around the world do not have an excellent diet.
Even at the current low RDAs, various studies in the U.S. and Canada have found that about a quarter to a third of people are marginally deficient in vitamin C, and up to 20 percent in some populations are severely deficient – including college students, who often have less-than-perfect diets. Smokers and older adults are also at significant risk.
Even marginal deficiency can lead to malaise, fatigue, and lethargy, researchers note. Healthier levels of vitamin C can enhance immune function, reduce inflammatory conditions such as atherosclerosis, and significantly lower blood pressure.
• A recent analysis of 29 human studies concluded that daily supplements of 500 milligrams of vitamin C significantly reduced blood pressure, both systolic and diastolic. High blood pressure is a major risk factor for heart disease and stroke, and directly attributes to an estimated 400,000 deaths annually in the U.S.
• A study in Europe of almost 20,000 men and women found that mortality from cardiovascular disease was 60 percent lower when comparing the blood plasma concentration of vitamin C in the highest 20 percent of people to the lowest 20 percent.
• Another research effort found that men with the lowest serum vitamin C levels had a 62 percent higher risk of cancer-related death after a 12-16 year period, compared to those with the highest vitamin C levels.
Laboratory studies with animals – which may be more accurate than human studies because they can be done in controlled conditions and with animals of identical genetic makeup - can document reasons that could explain all of these findings, Frei said.
Critics have suggested that some of these differences are simply due to better overall diet, not vitamin C levels, but the scientists noted in this report that some health benefits correlate even more strongly to vitamin C plasma levels than fruit and vegetable consumption.
Source : MedPage Today
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Dr. Mercola Talks Vitamin C
Vitamin C is required for the growth and repair of tissues in all parts of your body. It is necessary to form collagen, an important protein used to make skin, scar tissue, tendons, ligaments, and blood vessels. Vitamin C is essential for the healing of wounds, and for the repair and maintenance of cartilage, bones, and teeth.
Vitamin C is one of many antioxidants. Vitamin E and beta-carotene are two other well-known antioxidants. Antioxidants are nutrients that block some of the damage caused by free radicals, which are by-products that result when our bodies transform food into energy.
The build up of these by-products over time is largely responsible for the aging process and can contribute to the development of various health conditions such as cancer, heart disease, and a host of inflammatory conditions like arthritis. Antioxidants also help reduce the damage to the body caused by toxic chemicals and pollutants such as cigarette smoke.
The body does not manufacture vitamin C on its own, nor does it store it. It is therefore important to include plenty of vitamin C-containing foods in your daily diet.
All fruits and vegetables contain some amount of vitamin C. Foods that tend to be the highest sources of vitamin C include green peppers, citrus fruits and juices, strawberries, tomatoes, broccoli, turnip greens and other leafy greens, sweet and white potatoes, and cantaloupe.
Other excellent sources include papaya, mango, watermelon, brussels sprouts, cauliflower, cabbage, winter squash, red peppers, raspberries, blueberries, cranberries, and pineapples.
Read and listen (scroll to bottom) - Dr. Mercola and Dr. Hunninglake about the marvelous medicinal properties of Vitamin C
Vitamin C has taken a backseat in recent years with the advent of many newer antioxidants, but that doesn't make it any less important. Vitamin C is clearly the 'grandfather' of the traditional antioxidants we know of, and its potent health benefits have been clearly established.
Dr. Ronald Hunninghake is an internationally recognized expert on this vitamin. He got his start in this field about 22 years ago when he joined Dr. Hugh Riordan, who conducted research on intravenous (I.V.) vitamin C for cancer patients. His clinic is the successor to Linus Pauling and his work on vitamin C, and there is likely no clinic in the world with as much experience as his.
Dr. Hunninghake's Experience with Vitamin C for Cancer and Infectious Diseases Dr. Riordan carried on a 15-year long research project called RECNAC (cancer spelled backwards). His groundbreaking research in cell cultures showed that vitamin C was selectively cytotoxic against cancer cells.
Together, Hunninghake and Riordan conducted studies with a series of patients who had either stage 3 and stage 4 cancer.
"I.V. vitamin C was found to be very beneficial," Hunninghake says. "It's not considered a stand-alone therapy for cancer, but it's a perfect adjunct to any kind of therapy that the cancer patient is receiving at this time.
It will reduce side effects and improve quality of life. There have actually been two major studies now showing how it improves quality of life."
Cancer is clearly a life threatening disease, and most cancer patients also experience depression, pain, and tremendous fatigue – all of which can make treatment all the more difficult.
These are all signs of scurvy, which is the result of vitamin C deficiency… And if you actually measure vitamin C levels in cancer patients, especially advanced cancer patients, most, if not all, are vitamin C deficient, Hunninghake claims.
"One of the things that I.V. vitamin C does is it immediately relieves their scurvy symptoms," Hunninghake says. "So they start having a greater sense of well being. They don't need as much pain medicine. Their appetite improves. Their mood improves. They have a better quality of life."
Vitamin C may be better known, however, for its benefits for infectious diseases.
Dr. Hunninghake remarked:
"Certainly, anyone that's got a cold or a flu, or chronic fatigue, or any chronic viral infection, we do use [vitamin C].
… Dr. Levy wrote "Curing the Incurable," which is a fantastic book about vitamin C for infectious disease and toxin control. So certainly, I.V. vitamin C works very well for infectious diseases, as well as cancer."
A perfect example of the healing power of this antioxidant vitamin is the dramatic case of Allan Smith, who contracted a serious case of swine flu, and was brought back from the brink of death using a combination of IV and oral vitamin C. (Interestingly, Smith is now also free of the cancer he was diagnosed with while undergoing treatment for swine flu…)
"It's definitely a very underutilized modality in infectious disease," Hunninghake says.
"It's really a premiere treatment for any chronic infection. Again, it's not typically recognized by conventional medicine."
Why is Vitamin C Not a Widely Adopted Treatment Strategy? If vitamin C is so effective, why hasn't conventional medicine caught on?
Dr. Hunninghake tries to explain:
"I'm sure there are several factors here. Number one, most people think of vitamin C as a vitamin. You define vitamin as a trace amount of a substance that you need to prevent [ailments like] scurvy, in the case of vitamin C. But what we're talking about here is something in a pharmacological range.
The way to really understand vitamin C is to go back to the writings of Irwin Stone who wrote The Healing Factor, which was a fantastic book written in the 70s about vitamin C.
He points out that every creature, when they are sick, greatly increase their liver's or their kidney's production of vitamin C. But humans, primates, and guinea pigs have lost that ability.
We still have the gene that makes the L-gulonolactone oxidase enzyme that converts glucose to vitamin C but it's non-functional. We have to get our vitamin C from the outside; from food.
When we give vitamin C intravenously, what we're doing is recreating your liver's ability to synthesize tremendous amounts of vitamin C.
… So I always look upon high dose vitamin C as nature's way of dealing with crisis in terms of your health. This notion however does not exist in the conventional thinking in the medical mind."
There are also financial factors. The standard oncology treatments are extremely expensive while I.V. vitamin C is relatively inexpensive. And conventional medicine, as a general rule, is notoriously uninterested in solutions that can't produce profits.
Administration Methods and Dosage Recommendations There are two primary ways you can administer vitamin C; orally and intravenously.
"For the average patient, I… encourage them to take at least the Linus Pauling dose, which is 1 gram, twice a day, of vitamin C," Hunninghake says.
"Certainly you can do more than that. If you're suffering from chronic infections or chronic fatigue you can go ahead and gradually increase your dose up to what's called the bowel tolerance dose.
It's very safe. The idea that vitamin C causes kidney stones has been completely disproven... There have been several studies by urologists that have shown that is not an issue with high-dose vitamin C.
For the typical patient oral [supplementation] is fine, but if you have a serious illness, you should think in terms of doing intravenous vitamin C from a practitioner because it can greatly amplify and change the benefits of I.V. vitamin C."
As for the typical dosage for intravenous vitamin C, the Riordan IVC protocol calls for a starting dose around 15 grams.
However, it's important to first get your G6PD (Glucose-6-phosphate dehydrogenase)level checked.
Check for G6PD Deficiency Before Starting I.V. Vitamin C G6PD is an enzyme that your red blood cells need to maintain membrane integrity.
What many people don't understand is that high dose intravenous vitamin C is a strong pro-oxidant. And giving a pro-oxidant to a G6PD-deficient patient can cause hemolysis of their red blood cells.
So administering intravenous vitamin C is not for the novice.
I strongly recommend getting it done by an experienced practitioner who uses the Riordan protocol or some other protocol that ensures the vitamin C is administered in a safe manner.
Fortunately, G6PC deficiency is relatively uncommon. People of Mediterranean- and African decent are at greater risk, but it's rare even in those groups. In one series of over 800 G6PD tests, Hunninghake only found four people with a deficiency.
So it's not a great concern, but should you happen to be that rare person with a deficiency, the ramifications of barreling ahead with high dose I.V. vitamin C could be disastrous.
Dr. Riordan's original research suggested that you need to achieve a vitamin C blood level of around 300-350 mg/dl in order to achieve selective cytotoxicity. However, Hunninghake claims blood levels around 250 mg/dl may be sufficient to have an anti-cancer effect.
Dr. Hunninghake expounds on this issue:
"Now, just to put that into perspective for the average person, if we were to measure someone off the street, their blood level would be about 1 mg/dl if they're eating a fairly decent diet. If they're less than 0.6 mg per dl, they're into a scurvy type range of vitamin C.
But what we're talking about for a post-IVC saturation level, giving, let's say 25 to 50 grams of vitamin C intravenously over about a 90-minute period, is in the 200 to 300 mg/dl range.
So we're talking about 200 to 300 times the normal amount of vitamin C that your blood normally experiences just eating a balanced diet."
It's important to understand that these extremely high levels are really only indicated for the treatment cancers and infectious diseases, not for every-day, general health. This is becausevitamin C, which will always be an antioxidant, nevertheless starts to have a pro-oxidant effect at these extreme levels.
Interestingly, this pro-oxidant effect may actually be responsible for vitamin C's anti-cancerous properties…
"… At our second annual Riordan IVC and Cancer Conference held a few weeks ago in Japan, we had Dr. H. Chen, who was the author, along with Mark Levine, on high dose vitamin C as a source for creating hydrogen peroxide in the extracellular space surrounding tumor cells.
It's thought that it is this hydrogen peroxide, or pro-oxidant effect, of vitamin C that's causing the anti-tumor property. It's also that same pro-oxidant effect that, in fact, helps your body get rid of infectious disease."
To hear Dr. Hunninghake share some of the remarkable recoveries from difficult to treat cancers and other diseases, please listen to the interview in its entirety, or read through the transcript.
What You Need to Know About Oral Vitamin C The latest version of oral vitamin C supplementation is liposomal vitamin C, which I was introduced to by Dr. Thomas Levy, who is clearly one of the leaders in this area.
Liposomal vitamin C bypasses many of the complications of traditional vitamin C or ascorbic acid, and, according to Dr. Levy, you can achieve far higher intracellular concentrations this way.
"I'm all in favor of people trying this," Hunninghake says. "I think it can be used as an adjunct to I.V. vitamin C. Most people are only going to do I.V. vitamin C once or twice a week. So by doing the liposomal vitamin C, they can easily do 6 grams of liposomal vitamin C orally without a bit of gastrointestinal distress."
From Hunninghake's perspective, liposomal vitamin C may still be somewhat unproven, but is nonetheless quite safe.
There are also other forms of vitamin C on the market, such as buffered forms of sodium ascorbate. One example would be Ester-C. These buffered forms are also effective and do not cause the gastrointestinal distress associated with conventional ascorbic acid.
So far, I have recommended avoiding Ester-C, as I believe it's an oxidized form of vitamin C, which could do more harm than good. Dr. Hunninghake disagrees with my assessment, stating he's never seen any evidence indicating that Ester-C might be an oxidized form of vitamin C.
Based on Dr. Hunninghake's expertise in this area, I may reconsider my stance on Ester-C, although I still believe liposomal vitamin C has benefits that cannot be matched by buffered forms of vitamin C.
Dosing Frequency Can Also Make a Difference Another factor to keep in mind when taking oral vitamin C is dosing frequency.
Dr. Steve Hickey, who wrote the book Ascorbate, has shown that if you take vitamin C frequently throughout the day, you can achieve much higher plasma levels. So even though your kidneys will tend to rapidly excrete the vitamin C, by taking it every hour or two, you can maintain a much higher plasma level than if you just dose it once a day (unless you're taking an extended release form of vitamin C).
There are also a number of people, primarily with the naturopathic perspective, who believe that in order to be truly effective, ascorbic acid alone is not enough -- you need the combination of the ascorbic acid with its associated micronutrients, such as bioflavonoids and other components.
"There is no question that would be a better way to go. Any time you can [get it from] food, you're going to be better off… [F]ood is still the essential thing your body needs in order to get optimal cellular functioning.
But when you're sick, you can use trace nutrients in orthomolecular doses to achieve effects that you can't get from just food alone.
But in general, for people who are healthy and want to stay healthy, I would recommend using vitamin C that has bioflavonoids and other co-factors associated with it."
As far as getting your vitamin C from food, remember that the more colorful your diet, the higher it will be in bioflavanoids and cartenoids. Eating a colorful diet (i.e. plenty of vegetables) helps ensure you're naturally getting that phytonutrient synergism needed for maintaining health.
One of the easiest ways to ensure you're getting enough vegetables in your diet is by juicing them. For more information, please see my juicing page.
You can also squeeze some fresh lemon or lime juice into some water for a vitamin C rich beverage.
For More Information about Intravenous Vitamin C If you, or someone you know, want more information about using vitamin C as an adjunct to your cancer protocol, please visit www.RiordanClinic.org, where you can find the Riordan IVC Protocol discussed above. That site also contains a number of research articles so that you can review the evidence for yourself.
Dr. Hunninghake has also created a video on how vitamin C fights cancer, available at www.HealthHunterOnline.org.
This site also contains an informative lecture by Dr. Glen Hyland called IVC, Chemotherapy and Radiation - Are They Compatible? Hyland offers compelling evidence showing that not only are they compatible but they are synergistic.
Last but not least, for more details about vitamin C, its many health benefits, and the synergistic effects achieved when combined with other nutrients such as vitamin D, please listen to the entire interview as it contains much more than what I've summarized here.
Final Thoughts In closing, Dr. Hunninghake says:
"If you're going to treat cancer, you can't rely upon one modality. Even though we do kind of focus on I.V. vitamin C at our clinic, we measure nutrient levels.
We have people reexamine their diet. We encourage detoxification strategies, regular exercise, adequate sleep, improving interpersonal relationships… All of these can have a bearing on your outcome in cancer."
In my opinion, a cancer treatment plan that does not include testing and optimizing your vitamin D levels is nothing short of criminal negligence. Optimizing your vitamin D levels is just that important, especially if you have a disease like cancer.
In fact some experts believe that vitamin D is the "new" vitamin C. Of course they are not mutually exclusive and can be taken together, but I am still more of a fan of vitamin D as it really is a hormone and influences up to10 percent of your genes, which has very profound consequences if you are deficient.
However vitamin C also has great potential here, and there is overwhelming evidence showing that using I.V. vitamin C as an adjunct to conventional treatment methods can be extremely beneficial, with virtually no risk.
Source : Dr Mercola
LINK TO SOURCE
LISTEN TO DR. MERCOLA + DR HUNNINGHAKE TALK ABOUT VITAMIN C