COVID – Vitamin C breakthrough, Baricitinib dramatically improves Survival, Lockdowns and Endemics

This week in Data analysis we start building a face covering (mask) data frame and disease outbreaks. Breakthrough discoveries in Vitamin C and an Arthritis drug Baricitinib. As well as future disease outbreak concerns, vaccine hazards, and sars-cov-2 animal transmission. #covid19 #vitaminc #Baricitinib https://www.eurekalert.org/pub_releas… #sarsvac https://journals.plos.org/plosone/art… #polio https://www.pnas.org/content/115/5/10… #influenza https://www.eurekalert.org/pub_releas… #endemic https://science.sciencemag.org/conten… #zoo https://www.eurekalert.org/pub_releas… #lancetpred https://www.eurekalert.org/pub_releas… #arth

Muscle Mass and Vitamin C

“We know that Vitamin C consumption is linked with skeletal muscle mass. It helps defend the cells and tissues that make up the body from potentially harmful free radical substances. Unopposed these free radicals can contribute to the destruction of muscle, thus speeding up age-related decline.”

#vitaminc #muscle #skeletalmuscle

  1. Lucy N Lewis, Richard P G Hayhoe, Angela A Mulligan, Robert N Luben, Kay-Tee Khaw, Ailsa A Welch. Lower Dietary and Circulating Vitamin C in Middle- and Older-Aged Men and Women Are Associated with Lower Estimated Skeletal Muscle Mass. The Journal of Nutrition, 2020; DOI: 10.1093/jn/nxaa221

https://academic.oup.com/jn/article/150/10/2789/5897318

sarcopenia, skeletal muscle, frailty, vitamin C, ascorbic acid, muscle mass, muscle loss, aging, gain muscle, muscle growth, body mass index, diet ,frailty, skeletal muscles, plasma, ascorbic acid, sarcopenia, calcium ascorbate,

COVID-19 Updated Nutritional Supplement Research

COVID-19 Updated Nutritional Supplement Research

Dietary supplements an important weapon for fighting off COVID-19

Optimal Nutritional Status for a Well-Functioning Immune System Is an Important Factor to Protect against Viral Infections Nutrients 2020, 12(4), 1181; https://doi.org/10.3390/nu12041181

https://www.mdpi.com/2072-6643/12/4/1181/htm

Ayurveda and yoga for COVID-19 prevention

Public Health Approach of Ayurveda and Yoga for COVID-19 Prophylaxis Published Online:20 Apr 2020https://doi.org/10.1089/acm.2020.0129

https://www.liebertpub.com/doi/10.1089/acm.2020.0129

#Ashwagandha, #Dietarysupplements, #sars-cov-2

Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area JAMA. Published online April 22, 2020. doi:10.1001/jama.2020.6775

https://jamanetwork.com/journals/jama/fullarticle/2765184?guestAccessKey=906e474e-0b94-4e0e-8eaa-606ddf0224f5

Eurekalet

https://www.eurekalert.org/

Science Daily

https://www.sciencedaily.com/

Annals of Internal Medicine

https://annals.org/

Ayurveda, sars-cov-2, yoga, dietary supplements, immune system, , dosage, zinc, omega-3, dha, epa, nutritional status, mechanical ventilator, mortality, vitamin e, SARS coronavirus 2, Prophylaxis, immune system; viral infection; influenza; COVID-19; micronutrients, vitamins, omega-3 fatty acids, minerals, vitamin C, vitamin D, influenza, flu, virus,

Psoriasis Corrected in stem cell cultures with Vitamin C

Psoriasis Corrected in stem cell cultures with Vitamin C

Psoriasis Corrected in stem cell cultures with Vitamin C

Lian and Murphy have previously shown that 5-hmC loss in the skin epigenome can be reprogrammed using agents as fundamental as ascorbic acid (vitamin C). They reasoned that therapeutic correction of the epigenomic defect in psoriasis might reverse the entire process. Based on experiments using skin stem cell cultures in the lab, the team presents promising preliminary data suggesting that 5-hmC levels can be restored to correct the deficiency seen in psoriasis.

Loss of the Epigenetic Mark, 5-hmC, in Psoriasis: Implications for Epidermal Stem Cell Dysregulation Li, Feng et al. Journal of Investigative Dermatology DOI:https://doi.org/10.1016/j.jid.2019.10.016

https://www.jidonline.org/article/S0022-202X(19)33467-0/abstract

#psoriasis #vitaminc #ascorbicacid

Psoriasis, vitaminc, ascorbicacid, stemcells, 5-hmc, corrected, treated, reversed, stem cell, vitamin c, ascorbic acid, keratinocyte, 5-hydroxymethylcytosine, treatment

Vitamin C therapy linked to better survival rates after sepsis

Vitamin C therapy linked to better survival rates after sepsis

Vitamin C therapy linked to better survival rates after sepsis

Researchers discovered that intravenous vitamin C therapy reduced mortality in septic patients from 46% in the placebo group to almost 30% in the vitamin C group at day 28.

On average, the vitamin C group spent three fewer days in the ICU (seven days compared to 10) at day 28 and a week less in the hospital overall (15 days versus 22) by day 60 than the placebo group.

#vitaminc #sepsis #septic

Alpha A. Fowler, Jonathon D. Truwit, R. Duncan Hite, Peter E. Morris, Christine DeWilde, Anna Priday, Bernard Fisher, Leroy R. Thacker, Ramesh Natarajan, Donald F. Brophy, Robin Sculthorpe, Rahul Nanchal, Aamer Syed, Jamie Sturgill, Greg S. Martin, Jonathan Sevransky, Markos Kashiouris, Stella Hamman, Katherine F. Egan, Andrei Hastings, Wendy Spencer, Shawnda Tench, Omar Mehkri, James Bindas, Abhijit Duggal, Jeanette Graf, Stephanie Zellner, Lynda Yanny, Catherine McPolin, Tonya Hollrith, David Kramer, Charles Ojielo, Tessa Damm, Evan Cassity, Aleksandra Wieliczko, Matthew Halquist. Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure. JAMA, 2019; 322 (13): 1261 DOI: 10.1001/jama.2019.11825

https://jamanetwork.com/journals/jama/fullarticle/2752063

Vitamin c, ascorbic acid, intravenous, survival, treatment, organ, hospital stay, better, Acute respiratory distress syndrome, ARDS, vitamin C infusions, cure, Vascular Injury, lung injury

Heart Failure improved with Antioxidant Combination

Heart Failure improved with Antioxidant Combination

Heart Failure improved with Antioxidant Combination

“””the measure of function in large blood vessels and of inflammation improved with treatment. Similarly, the presence of biologically available nitric oxide, a compound that helps blood vessels dilate, also increased.””

Over-the-counter Antioxidant Cocktail Improved Vascular Function in Certain Patients with Heart Failure – The American Physiological Society Press Release April 9, 2019

http://www.the-aps.org/mm/hp/Audiences/Public-Press/2019-22.html

Antidepressant foods: An evidence-based nutrient profiling system for depression

Antidepressant foods: An evidence-based nutrient profiling system for depression

Antidepressant foods: An evidence-based nutrient profiling system for depression

The objective of this study is to determine which foods are the most nutrient dense sources of nutrients demonstrated by human studies published in the current scientific literature to play a role in the prevention and promotion of recovery from depressive disorders.

LaChance LR, Ramsey D. Antidepressant foods: An evidence-based nutrient profiling system for depression. World J Psychiatry 2018; 8(3): 97-104

Dietary antioxidants may help repair the Lungs

Dietary antioxidants may help repair the Lungs

Over a 10 year period researchers observed that regular intake of tomatoes may help slow the natural decline in lung function among all adults as well as other findings.

Dietary antioxidants and ten-year lung function decline in adults from the ECRHS survey. European Respiratory Journal, December 2017 DOI: 10.1183/13993003.02286-2016

A Cure for Sepsis ?

 

Highlights: – discovered that a single bolus of vitamin C injected early at the time of induction of sepsis, prevents capillary plugging. He has also found that a delayed bolus injection of vitamin C can  reverse plugging by restoring blood flow in previously plugged capillaries – found that early as well as delayed injections of vitamin C improves chance of survival significantly – the beneficial effect of a single bolus injection of vitamin C is long lasting and prevents capillary plugging for up to 24  hours post-injection – Previous studies have shown that it can be injected intravenously into patients with no side effects * University of Western Ontario and Lawson Health Research Institute NOV 2010 Continue reading “A Cure for Sepsis ?”

Subclinical deficiencies of vitamin C and D have each been linked to psychological abnormalities

Public release date: 23-Sep-2010 HRR: Requested Repost

– Patients administered vitamin C had a rapid and statistically and clinically significant improvement in mood state

“About one in five acute-care patients in our hospital have vitamin C levels so low as to be compatible with scurvy,”

Happy Smiley Face from Urine Samples

Subclinical deficiencies of vitamin C and D have each been linked to psychological abnormalities

Simple treatment may counteract widespread problem of subnormal vitamin levels in acute-care patients Continue reading “Subclinical deficiencies of vitamin C and D have each been linked to psychological abnormalities”

Vitamin C Helps Control Gene Activity in Stem Cells

Vitamin C, in a natural source such as an orange and as a supplement. Vitamin C affects whether genes are switched on or off inside mouse stem cells, and may thereby play a previously unknown and fundamental role in helping to guide normal development in mice, humans and other animals. (Credit: © brozova / Fotolia)

July 1, 2013 — Vitamin C affects whether genes are switched on or off inside mouse stem cells, and may thereby play a previously unknown and fundamental role in helping to guide normal development in mice, humans and other animals, a scientific team led by UC San Francisco researchers has discovered.

The researchers found that vitamin C assists enzymes that play a crucial role in releasing the brakes that keep certain genes from becoming activated in the embryo soon after fertilization, when egg and sperm fuse.

The discovery might eventually lead to the use of vitamin C to improve results of in vitro fertilization, in which early embryos now are typically grown without the vitamin, and also to treat cancer, in which tumor cells abnormally engage or release these brakes on gene activation, the researchers concluded in a study published June 30, 2013 in the journal Nature.

In the near term, stem-cell scientists may begin incorporating vitamin C more systematically into their procedures for growing the most healthy and useful stem cells, according to UCSF stem-cell scientist Miguel Ramalho-Santos, PhD, who led the study. In fact, the unanticipated discovery emerged from an effort to compare different formulations of the growth medium, a kind of nutrient broth used to grow mouse embryonic stem cells in the lab.

Rather than building on any previous body of scientific work, the identification of the link between vitamin C and the activation of genes that should be turned on in early development was serendipitous, Ramalho-Santos said. “We bumped into this result,” he said.

Working in Ramalho-Santos’ lab, graduate student Kathryn Blaschke and postdoctoral fellow Kevin Ebata, PhD, were comparing different commercial growth media for mouse stem cells. The researchers began exploring how certain ingredients altered gene activity within the stem cells. Eventually they discovered that adding vitamin C led to increased activity of key enzymes that release the brakes that can prevent activation of an array of genes.

The brakes on gene activation that vitamin C helps release are molecules called methyl groups. These methyl groups are added to DNA at specific points along the genome to prevent specific genes from getting turned on.

During the development of multicellular organisms, humans among them, different patterns of methylation arise in different cells as methyl groups are biochemically attached to DNA at specific points along the genome during successive cell divisions. Normally this gradual methylation, a key part of the developmental program, is not reversible.

But after fertilization and during early development, a class of enzymes called “Tet” acts on a wide array of the methyl groups on the DNA to remove these brakes, so that genes can be activated as needed.

The UCSF researchers demonstrated that Tet enzymes require vitamin C for optimal activity as they act to remove the methyl groups from the DNA and to stimulate gene activity that more faithfully mimics in cultured stem cells what occurs at early stages of development in the mouse embryo.

“Potential roles for vitamin C in the clinic — including in embryo culture media used during in vitro fertilization, which currently do not contain vitamin C, and in cancers driven by aberrant DNA methylation — deserve exploration,” Ramalho-Santos, said.

In addition, scientists previously have found that many adult tissues also have stem cells, which can generate a variety of cell types found within a specific tissue. This raises the possibility that vitamin C might help maintain healthy stem cell populations in the adult, according to Ramalho-Santos.

“Although we did not in this paper address the function of Vitamin C in adult tissues, given the roles that Tet enzymes are now known to play in adult tissues, we anticipate that Vitamin C might also regulate Tet function in the adult,” Ramalho-Santos said. “This remains to be determined.”

Vitamin C already has become a popular supplement in recent decades, and potential health benefits of vitamin C supplementation continue to be investigated in clinical trials. It has been more than 80 years since vitamin C was first recognized as vital to prevent scurvy, a now rare connective-tissue disease caused by the failure of another enzyme that also relies on vitamin C.

The function of vitamin C as an antioxidant to prevent chemical damage is the likely reason why some commercial suppliers of growth media have included it in their products, Ramalho-Santos said, but other antioxidant molecules cannot replace Vitamin C in the enhancement of the activity of Tet enzymes.

Despite its importance, humans, unlike most animals and plants, cannot synthesize their own Vitamin C and must obtain it through their diet. The mouse makes vitamin C, but that fact does not diminish the expectation that the new findings will also apply to human development, according to Ramalho-Santos. Only adult liver cells in the mouse make vitamin C, he said.

Ramalho-Santos now aims to explore the newly discovered phenomenon in the living mouse. “The next step is to study vitamin C and gene expression in vivo,” he said.

 

http://www.sciencedaily.com/releases/2013/07/130701163755.htm

Foetus suffers when mother lacks vitamin C

Healthy pregnancy

Maternal vitamin C deficiency during pregnancy can have serious consequences for the foetal brain. And once brain damage has occurred, it cannot be reversed by vitamin C supplements after birth. This is shown through new research at the University of Copenhagen just published in the scientific journal PLOS ONE.

vitamin C supplements are important during pregnancy.
Photo: Wikimedia Commons af Tom & Katrien.

Population studies show that between 10-20 per cent of all adults in the developed world suffer from vitamin C deficiency. Therefore, pregnant women should think twice about omitting the daily vitamin pill.

“Even marginal vitamin C deficiency in the mother stunts the foetal hippocampus, the important memory centre, by 10-15 per cent, preventing the brain from optimal development,” says Professor Jens Lykkesfeldt. He heads the group of scientists that reached this conclusion by studying pregnant guinea pigs and their pups. Just like humans, guinea pigs cannot produce vitamin C themselves, which is why they were chosen as the model.

“We used to think that the mother could protect the baby. Ordinarily there is a selective transport from mother to foetus of the substances the baby needs during pregnancy. However, it now appears that the transport is not sufficient in the case of vitamin C deficiency. Therefore it is extremely important to draw attention to this problem, which potentially can have serious consequences for the children affected,” says Jens Lykkesfeldt.

Too late when damage is done

The new results sharpen the focus on the mother’s lifestyle and nutritional status during pregnancy. The new study has also shown that the damage done to the foetal brain cannot be repaired, even if the baby is given vitamin C after birth.
When the vitamin C deficient guinea pig pups were born, scientists divided them into two groups and gave one group vitamin C supplements. However, when the pups were two months old, which corresponds to teenage in humans, there was still no improvement in the group that had been given supplements.
The scientists are now working to find out how early in the pregnancy vitamin C deficiency influences the development of foetal guinea pigs. Preliminary results show that the impact is already made early in the pregnancy, as the foetuses were examined in the second and third trimesters. Scientists hope in the long term to be able to use population studies to illuminate the problem in humans.

Vulnerable groups

There are some groups that may be particularly vulnerable of vitamin C deficiency:
“People with low economic status who eat poorly – and perhaps also smoke – often suffer from vitamin C deficiency. Comparatively speaking, their children risk being born with a poorly developed memory potential. These children may encounter learning problems, and seen in a societal context, history repeats itself because these children find it more difficult to escape the environment into which they are born,” says Jens Lykkesfeldt.
He emphasises that if pregnant women eat a varied diet, do not smoke, and for instance take a multi-vitamin tablet daily during pregnancy, there is no reason to fear vitamin C deficiency.
“Because it takes so little to avoid vitamin C deficiency, it is my hope that both politicians and the authorities will become aware that this can be a potential problem,” concludes Jens Lykkesfeldt.

Read the article in the scientific journal PLOS ONE.

Contact

Professor Jens Lykkesfeldt, Department of Veterinary Disease Biology, Biomedicine
Phone: +45 35333125

The FASEB Journal reports vitamin C reverses abnormalities caused by Werner syndrome gene, including cancer, obesity, diabetes, heart failure and high cholesterol

2009 study posted for filing

Contact: Cody Mooneyhan cmooneyhan@faseb.org 301-634-7104 Federation of American Societies for Experimental Biology

New year, new vitamin C discovery: It ‘cures’ mice with accelerated aging disease

New research in the FASEB Journal reports vitamin C reverses abnormalities caused by Werner syndrome gene, including cancer, obesity, diabetes, heart failure and high cholesterol

A new research discovery published in the January 2010 print issue of the FASEB Journal (http://www.fasebj.org) suggests that treatments for disorders that cause accelerated aging, particularly Werner’s syndrome, might come straight from the family medicine chest. In the research report, a team of Canadian scientists show that vitamin C stops and even reverses accelerated aging in a mouse model of Werner’s syndrome, but the discovery may also be applicable to other progeroid syndromes. People with Werner’s syndrome begin to show signs of accelerated aging in their 20s and develop age-related diseases and generally die before the age of 50.

“Our study clearly indicates that a healthy organism or individuals with no health problems do not require a large amount of vitamin C in order to increase their lifespan, especially if they have a balanced diet and they exercise,” said Michel Lebel, Ph.D., co-author of the study from the Centre de Recherche en Cancerologie in Quebec, Canada. “An organism or individual with a mutation in the WRN gene or any gene affected by the WRN protein, and thus predisposes them to several age-related diseases, may benefit from a diet with the appropriate amount of vitamin C.”

Scientists treated both normal mice and mice with a mutation in the gene responsible for Werner’s syndrome (WRN gene) with vitamin C in drinking water. Before treatment, the mice with a mutated WRN gene were fat, diabetic, and developing heart disease and cancer. After treatment, the mutant mice were as healthy as the normal mice and lived a normal lifespan. Vitamin C also improved how the mice stored and burned fat, decreased tissue inflammation and decreased oxidative stress in the WRN mice. The healthy mice did not appear to benefit from vitamin C.

“Vitamin C has become one of the most misunderstood substances in our medicine cabinets and food,” said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal. “This study and others like it help explain how and why this chemical can help to defend some, but certainly not all, people from premature senescence.”

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Receive monthly highlights from The FASEB Journal by e-mail. Sign up at http://www.faseb.org/fasebjournalreaders.htm. The FASEB Journal (http://www.fasebj.org) is published by the Federation of the American Societies for Experimental Biology (FASEB). The journal has been recognized by the Special Libraries Association as one of the top 100 most influential biomedical journals of the past century and is the most cited biology journal worldwide according to the Institute for Scientific Information. FASEB is composed of 23 societies with more than 90,000 members, making it the largest coalition of biomedical research associations in the United States. FASEB enhances the ability of biomedical and life scientists to improve-through their research-the health, well-being and productivity of all people. Its mission is to advance health and welfare by promoting progress and education in biological and biomedical sciences through service to our member societies and collaborative advocacy.

Details: Laurent Massip, Chantal Garand, Eric R. Paquet, Victoria C. Cogger, Jennifer N. O’Reilly, Leslee Tworek, Avril Hatherell, Carla G. Taylor, Eric Thorin, Peter Zahradka, David G. Le Couteur, and Michel Lebel. Vitamin C restores healthy aging in a mouse model for Werner syndrome. FASEB J. 2010 24: 158-172. http://www.fasebj.org/cgi/content/abstract/24/1/158

Stopping diabetes damage with vitamin C

2009 study posted for filing

Contact: Diane Clay
diane-clay@ouhsc.edu
405-271-2323
University of Oklahoma

First test in humans gets dramatic results from blood sugar control and antioxidant

Researchers at the Harold Hamm Oklahoma Diabetes Center have found a way to stop the damage caused by Type 1 diabetes with the combination of insulin and a common vitamin found in most medicine cabinets.

While neither therapy produced desired results when used alone, the combination of insulin to control blood sugar together with the use of Vitamin C, stopped blood vessel damage caused by the disease in patients with poor glucose control. The findings appear this week in the Journal of Clinical Endocrinology and Metabolism.

“We had tested this theory on research models, but this is the first time anyone has shown the therapy’s effectiveness in people,” said Michael Ihnat, Ph.D., principal investigator and a pharmacologist at the OU College of Medicine Department of Cell Biology.

Ihnat said they are now studying the therapy in patients with Type 2 diabetes.

The goal of the work being done by Ihnat and British scientists from the University of Warwick led by Dr. Antonio Ceriello is to find a way to stop the damage to blood vessels that is caused by diabetes. The damage, known as endothelial dysfunction, is associated with most forms of cardiovascular disease such as hypertension, coronary artery disease, chronic heart failure, peripheral artery disease, diabetes and chronic renal failure.

By reducing or stopping the damage, patients with diabetes could avoid some of the painful and fatal consequences of the disease that include heart disease, reduced circulation and amputation, kidney disease and diabetic retinopathy, which can lead to blindness.

Insulin and many other drugs have long been used to control blood sugar, but Ihnat – in an earlier project with scientists in Italy and Hungary – found that cells have a “memory” that causes damage to continue even when blood sugar is controlled. By adding antioxidants like Vitamin C, Ihnat found that cell “memory” disappeared and cell function and oxidation stress were normalized.

“We have speculated that this happens with endothelial dysfunction, but we did not know until now if it was effective in humans. We finally were able to test it and proved it to be true,” Ihnat said. “For patients with diabetes, this means simply getting their glucose under control is not enough. An antioxidant-based therapy combined with glucose control will give patients more of an advantage and lessen the chance of complications with diabetes.”

While researchers do suggest diabetic patients eat foods and take multivitamins rich in antioxidants like Vitamin C, they warn that additional study is needed. The Vitamin C utilized in their study was given at very high doses and administered directly into the blood stream, so it is unlikely someone would get similar results with an over-the-counter vitamin supplement.

The team is now working to determine how antioxidants work at the molecular level to halt the destructive chain reaction set in motion by high blood sugar levels. In addition, they are evaluating several other antioxidants with an ultimate hope that their work will translate into simple, effective and inexpensive treatments for the control of diabetes.

 

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The Journal of Clinical Endocrinology & Metabolism is the world’s leading peer-reviewed journal for endocrine clinical research and cutting-edge clinical practice reviews.

Dr. Ihnat’s latest work, which is funded by the VA Medical Center, can be found online at http://jcem.endojournals.org/cgi/content/abstract/jc.2009-0762v1.

Vitamin C intake associated with lower risk of gout in men

Contact: Gina DiGravio
gina.digravio@bmc.org
617-638-8491
JAMA and Archives Journals

Men with higher vitamin C intake appear less likely to develop gout, a painful type of arthritis, according to a report in the March 9 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

“Gout is the most common type of inflammatory arthritis in men,” the authors write as background information in the article. “Epidemiologic studies suggest that the overall disease burden of gout is substantial and growing. The identification of the risk factors for gout that are modifiable with available measures is an important first step in the prevention and management of this common and excruciatingly painful condition.”

Hyon K. Choi, M.D., Dr.P.H., then of University of British Columbia, Vancouver, and now of Boston University School of Medicine, and colleagues examined the relationship between vitamin C intake and gout in 46,994 men between 1986 and 2006. Every four years, the men completed a dietary questionnaire, and their vitamin C intake through food and supplements was computed. Every two years, participants reported whether they had been diagnosed with or developed symptoms of gout.

During 20 years of follow-up, 1,317 men developed gout. Compared with men who had a vitamin C intake of less than 250 milligrams per day, the relative risk of gout was 17 percent lower for those with a daily intake of 500 to 999 milligrams, 34 percent lower for those with an intake of 1,000 to 1,499 milligrams per day and 45 percent lower for those with an intake of 1,500 milligrams per day or higher. For every 500-milligram increase in their vitamin C intake, men’s risk for gout appeared to decrease by 17 percent. Compared with men who did not take vitamin C supplements, those who took 1,000 to 1,499 supplemental milligrams per day had a 34 percent lower risk of gout and those who took 1,500 supplemental milligrams per day had a 45 percent lower risk.

Vitamin C appears to reduce levels of uric acid in the blood, the authors note; a buildup of this naturally occurring compound can form crystal deposits in and around joints, leading to the pain, inflammation and swelling associated with gout. Vitamin C may affect reabsorption of uric acid by the kidneys, increase the speed at which the kidneys work or protect against inflammation, all of which may reduce gout risk, the authors note.

“Given the general safety profile associated with vitamin C intake, particularly in the generally consumed ranges as in the present study (e.g., tolerable upper intake level of vitamin C of less than 2,000 milligrams in adults according to the Food and Nutrition Board, Institute of Medicine), vitamin C intake may provide a useful option in the prevention of gout,” they conclude.

 

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(Arch Intern Med. 2009;169[5]:502-507. Available pre-embargo to the media at www.jamamedia.org.)

Editor’s Note: This work was supported in part by grants from the National Institutes of Health and by TAP Pharmaceuticals. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Mount Sinai School of Medicine study shows vitamin C prevents bone loss in animal models

Contact: Jeanne Bernard Jeanne.Bernard@mountsinai.org 212-241-9200 The Mount Sinai Hospital / Mount Sinai School of Medicine

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.”

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About The Mount Sinai Medical Center

The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Mount Sinai School of Medicine. Established in 1968, Mount Sinai School of Medicine is one of the leading medical schools in the United States. The Medical School is noted for innovation in education, biomedical research, clinical care delivery, and local and global community service. It has more than 3,400 faculty in 32 departments and 14 research institutes, and ranks among the top 20 medical schools both in National Institutes of Health (NIH) funding and by U.S. News & World Report.

The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation’s oldest, largest and most-respected voluntary hospitals. In 2012, U.S. News & World Report ranked The Mount Sinai Hospital 14th on its elite Honor Roll of the nation’s top hospitals based on reputation, safety, and other patient-care factors. Mount Sinai is one of 12 integrated academic medical centers whose medical school ranks among the top 20 in NIH funding and by  U.S. News & World Report and whose hospital is on the U.S. News & World Report Honor Roll.  Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 560,000 outpatient visits took place.

For more information, visit http://www.mountsinai.org/.

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Vitamin D, may protect us from background radiation and could be used as a safe protective agent before or after a low-level nuclear incident

2008 study re-posted for filing

Contact: Daniel Hayes
dhayes@health.nyc.gov
Inderscience Publishers

Could vitamin D save us from radiation?

Radiological health expert Daniel Hayes, Ph.D., of the New York City Department of Health and Mental Hygiene suggests that a form of vitamin D could be one of our body’s main protections against damage from low levels of radiation. Writing in the International Journal of Low Radiation, Hayes explains that calcitriol, the active form of vitamin D, may protect us from background radiation and could be used as a safe protective agent before or after a low-level nuclear incident.

Biologists and pharmacologists who specialize in radiation and health are keen to find an effective agent that could be given by mouth, have few side effects and would protect us against a suspected or impending nuclear event, whether an accident, terrorist attack, or other incident.

In terms of protecting people from the long-term effects of radiation, cancer formation would be the main focus. The ideal agent would act by blocking DNA damage or by halting the progression of damaged cells that might eventually grow into cancers.

While a drug is yet to be found with such ideal radio-protective properties, other researchers have demonstrated that certain dietary supplements have at least some of the desired properties. Hayes argues that vitamin D, and in particular its biologically active form, could be the key ingredient in radiological protection.

“Our general understanding and appreciation of the multifaceted protective actions of vitamin D have recently entered a new era,” says Hayes, “It is now becoming recognized that its most active molecular form, 1,25-dihydroxyvitamin D3, may offer protection against a variety of radiation- and otherwise-induced damages.”

Hayes has reviewed the various biochemical mechanisms by which vitamin D protects users_ from the low levels of natural radiation released by the rocks on which we stand and the skies above us. He points out that calcitriol is involved in cell cycle regulation and control of proliferation, cellular differentiation and communication between cells, as well as programmed cell death (apoptosis and autophagy) and antiangiogenesis.

Calcitriol is the form of vitamin D that activates the body’s Vitamin D Receptor (VDR), which allows gene transcription to take place and the activation of the innate immune response.

It is possible that several of the transcribed by the VDR will help transcribe proteins that protect the body against radiation.

“Vitamin D by its preventive/ameliorating actions should be given serious consideration as a protective agent against sublethal radiation injury, and in particular that induced by low-level radiation,” concludes Hayes.

Vitamin C injections slow tumor growth in mice

Repost 2008

Contact: Joan Chamberlain niddkmedia@mail.nih.gov 301-496-3583 NIH/National Institute of Diabetes and Digestive and Kidney Diseases

High-dose injections of vitamin C, also known as ascorbate or ascorbic acid, reduced tumor weight and growth rate by about 50 percent in mouse models of brain, ovarian, and pancreatic cancers, researchers from the National Institutes of Health (NIH) report in the August 5, 2008, issue of the Proceedings of the National Academy of Sciences.  The researchers traced ascorbate’s anti-cancer effect to the formation of hydrogen peroxide in the extracellular fluid surrounding the tumors.  Normal cells were unaffected.

Natural physiologic controls precisely regulate the amount of ascorbate absorbed by the body when it is taken orally.  “When you eat foods containing more than 200 milligrams of vitamin C a day–for example, 2 oranges and a serving of broccoli–your body prevents blood levels of ascorbate from exceeding a narrow range,” says Mark Levine, M.D., the study’s lead author and chief of the Molecular and Clinical Nutrition Section of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the NIH.  To bypass these normal controls, NIH scientists injected ascorbate into the veins or abdominal cavities of rodents with aggressive brain, ovarian, and pancreatic tumors.  By doing so, they were able to deliver high doses of ascorbate, up to 4 grams per kilogram of body weight daily.  “At these high injected doses, we hoped to see drug-like activity that might be useful in cancer treatment,” said Levine.

Vitamin C plays a critical role in health, and a prolonged deficiency leads to scurvy and eventually to death.  Some proteins known as enzymes, which have vital biochemical functions, require the vitamin to work properly.  Vitamin C may also act as an antioxidant, protecting cells from the damaging effects of free radicals.  The NIH researchers, however, tested the idea that ascorbate, when injected at high doses, may have prooxidant instead of antioxidant activity.  Prooxidants would generate free radicals and the formation of hydrogen peroxide, which, the scientists hypothesized, might kill tumor cells.  In their laboratory experiments on 43 cancer and 5 normal cell lines, the researchers discovered that high concentrations of ascorbate had anticancer effects in 75 percent of cancer cell lines tested, while sparing normal cells.  In their paper, the researchers also showed that these high ascorbate concentrations could be achieved in people.

The team then tested ascorbate injections in immune-deficient mice with rapidly spreading ovarian, pancreatic, and glioblastoma (brain) tumors.  The ascorbate injections reduced tumor growth and weight by 41 to 53 percent.  In 30 percent of glioblastoma controls, the cancer had spread to other organs, but the ascorbate-treated animals had no signs of disseminated cancer.  “These pre-clinical data provide the first firm basis for advancing pharmacologic ascorbate in cancer treatment in humans,” the researchers conclude.

Interest in vitamin C as a potential cancer therapy peaked about 30 years ago when case series data showed a possible benefit.  In 1979 and 1985, however, other researchers reported no benefit for cancer patients taking high oral doses of vitamin C in two double-blind, placebo-controlled clinical trials.

Several observations led the NIH researchers to revisit ascorbate as a cancer therapy.  “Clinical and pharmacokinetic studies conducted in the past 12 years showed that oral ascorbate levels in plasma and tissue are tightly controlled.  In the case series, ascorbate was given orally and intravenously, but in the trials ascorbate was just given orally.  It was not realized at the time that only injected ascorbate might deliver the concentrations needed to see an anti-tumor effect,” said Levine, who noted that new clinical trials of ascorbate as a cancer treatment are in the planning stages.

Data from Levine’s earlier studies of the regulation and absorption of dietary vitamin C were used in the revision of the Institute of Medicine’s Recommended Dietary Allowance for the vitamin in 2000.  In the current study, Levine led a team of scientists from the NIDDK and the National Cancer Institute (NCI), both components of the NIH, as well as the University of Kansas.  “NIH’s unique translational environment, where researchers can pursue intellectual high-risk, out-of-the-box thinking with high potential payoff, enabled us to pursue this work,” he said.

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For more information about cancer, please visit the NCI website at www.cancer.gov, or call NCI’s Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

The NIDDK conducts and supports research in diabetes and other endocrine and metabolic diseases; digestive diseases, nutrition, and obesity; and kidney, urologic, and hematologic diseases.  Spanning the full spectrum of medicine and afflicting people of all ages and ethnic groups, these diseases encompass some of the most common, severe, and disabling conditions affecting Americans. For more information about NIDDK and its programs, see www.niddk.nih.gov.

The National Institutes of Health (NIH) — The Nation’s Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services.  It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases.  For more information about NIH and its programs, see www.nih.gov.

Vitamin C and beta-carotene might protect against dementia

Contact: Willi Baur willi.baur@uni-ulm.de 49-731-502-2020 IOS Press

Study examines the influence of antioxidants on the pathogenesis of Alzheimer’s disease

Forgetfulness, lack of orientation, cognitive decline… about 700, 000 Germans suffer from Alzheimer’s disease (AD). Now researchers from the University of Ulm, among them the Epidemiologist Professor Gabriele Nagel and the Neurologist Professor Christine von Arnim, have discovered that the serum-concentration of the antioxidants vitamin C and beta-carotene are significantly lower in patients with mild dementia than in control persons. It might thus be possible to influence the pathogenesis of AD by a person’s diet or dietary antioxidants. 74 AD-patients and 158 healthy controls were examined for the study that has been published in the “Journal of Alzheimer’s Disease” (JAD).

AD is a neurodegenerative disease: Alterations in the brain caused by amyloid-beta-plaques, degeneration of fibrillae and a loss of synapses are held responsible for the characteristic symptoms. Oxidative stress, which constrains the exploitation of oxygen in the human body, is suspected to promote the development of AD. Whereas so called antioxidants might protect against neurodegeneration. In their study, the researchers have investigated whether the serum-levels of vitamin C, vitamin E, beta-carotene as well as lycopene and coenzyme Q10 are significantly lower in the blood of AD-patients. “In order to possibly influence the onset and development of Alzheimer’s disease, we need to be aware of potential risk factors”, says Gabriele Nagel.

Participants were recruited from the cross-sectional study IMCA ActiFE (Activity and Function in the Elderly in Ulm) for which a representative population-based sample of about 1,500 senior citizens has been examined. The 65 to 90 years old seniors from Ulm and the surrounding area underwent neuropsychological testing and answered questions regarding their lifestyle. What is more, their blood has been examined and their body mass index (BMI) was calculated. For the present study, scientists have compared 74 patients with mild dementia (average age 78.9 years) with a control group consisting of 158 healthy, gender-matched persons of the same age. Results are quite interesting: The concentration of vitamin C and beta-carotene in the serum of AD-patients was significantly lower than in the blood of control subjects. Whereas no such difference between the groups could be found for the other antioxidants (vitamin E, lycopene, coenzyme Q10). Potential confounding factors such as education, civil status, BMI, consumption of alcohol and tobacco have been considered in the statistical analysis. Nevertheless, additional parameters such as the storage and preparation of food as well as stressors in the life of participants might have influenced the findings. Therefore, results need to be confirmed in prospective surveys. “Longitudinal studies with more participants are necessary to confirm the result that vitamin C and beta-carotene might prevent the onset and development of Alzheimer’s disease”, says Gabriele Nagel. Vitamin C can for example be found in citrus fruits; beta-carotene in carrots, spinach or apricots.

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The study has been supported by the Ministry of Science, Research and the Arts of Baden-Württemberg (as part of the Geriatric Competence Center Ulm) and by the European Union. Further authors from the University of Ulm comprise Professor Albert Ludolph (Director of the Department of Neurology) and Professor Matthias Riepe, Department of Psychiatry and Psychotherapy II, as well as Professor Richard Peter and Florian Herbolsheimer (Institute of Epidemiology and Medical Biometry). Professor Thorsten Nikolaus (Geriatric Competence Center Ulm) and Professor Hans Biesalski (University of Hohenheim) have also contributed to the study

Vitamin C: A potential life-saving treatment for sepsis

Contact: Kathy Wallis kwallis3@uwo.ca 519-661-2111 x81136 University of Western Ontario

Vitamin C: A potential life-saving treatment for sepsis

Physicians caring for patients with sepsis may soon have a new safe and cost-effective treatment for this life-threatening illness.  Research led by Dr. Karel Tyml and his colleagues at The University of Western Ontario and Lawson Health Research Institute have found that vitamin C can not only prevent the onset of sepsis, but can reverse the disease.

Sepsis is caused by a bacterial infection that can begin anywhere in your body.  Your immune system goes into overdrive, overwhelming normal processes in your blood. The result is that small blood clots form, blocking blood flow to vital organs. This can lead to organ failure. Babies, the elderly and those with weakened immune systems are most likely to get sepsis. But even healthy people can become deathly ill from the disease.

According to Dr. Tyml, a professor at Western’s Schulich School of Medicine & Dentistry, patients with severe sepsis have a high mortality rate, nearly 40 percent, because there is no effective treatment.

“There are many facets to sepsis, but the one we have focused on for the past 10 years is the plugging of capillaries,” says Dr. Tyml.  Plugged capillaries prevent oxygenation and the supply of life-supporting materials to your organ tissue and stop the removal of metabolic waste product.  Plugged capillaries are seen in organs of septic patients.  These organs may eventually fail, leading to multiple organ failure and death.  Dr. Tyml’s lab was the first to discover this plugging by using intravital microscopy, a technique Dr. Tyml pioneered in Canada.

According to Dr. Tyml’s most recent publication, oxidative stress and the activated blood clotting pathway are the major factors responsible for the capillary plugging in sepsis. Through his research, Dr. Tyml has discovered that a single bolus of vitamin C injected early at the time of induction of sepsis, prevents capillary plugging.  He has also found that a delayed bolus injection of vitamin C can reverse plugging by restoring blood flow in previously plugged capillaries.

“Our research in mice with sepsis has found that early as well as delayed injections of vitamin C improves chance of survival significantly,” explains Dr. Tyml.  “Furthermore, the beneficial effect of a single bolus injection of vitamin C is long lasting and prevents capillary plugging for up to 24 hours post-injection.”

Dr. Tyml and his colleagues are eager to find appropriate support to move this research from the bench to the bedside to see if these findings translate to patients with sepsis.

The potential benefit of this treatment is substantial.  “Vitamin C is cheap and safe. Previous studies have shown that it can be injected intravenously into patients with no side effects,” says Dr. Tyml.  “It has the potential to significantly improve the outcome of sepsis patients world-wide.  This could be especially beneficially in developing countries where sepsis is more common and expensive treatments are not affordable.”

* Reposted for Category Submission

Increase in RDA for vitamin C could help reduce heart disease, stroke, cancer

 

CORVALLIS, Ore. – 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.

Scientists in France and Denmark collaborated on this report. Research at OSU on these issues has been supported by the National Center for Complementary and Alternative Medicine, a division of the National Institutes of Health.

About the Linus Pauling Institute: The Linus Pauling Institute at OSU is a world leader in the study of micronutrients and their role in promoting optimum health or preventing and treating disease. Major areas of research include heart disease, cancer, aging and neurodegenerative disease

Sepsis: Blood Poisoning Kills Thousands, But No Drugs to Help / Vitamin C: A potential life-saving treatment for sepsis

Rory Staunton’s death started with a simple cut on his arm.

Rory, a 12-year-old New Yorker, cut himself when he dove for a basketball at his school gym in late March, according to the New York Times. Two days later, he was vomiting, feverish and had a pain in his leg. A few days later, on April 1, Rory died at NYU-Langone Medical Center of a kind of blood poisoning known as sepsis.

His death, and others, point to a major problem in treating sepsis — there are currently no drugs approved to fight it. The only drug developed for it, called Xigris, was withdrawn from the market in 2011, when the drug failed rigorous testing required to maintain regulatory approval. The drug’s fall from grace highlights just how difficult fighting sepsis is, and leaves doctors wondering whether developing a drug will ever be possible.

Bleak Prognosis, Then Brief Promise

About 750,000 people in the U.S. each year get sepsis, and about 225,000 of them die from it. The condition is an infection of the bloodstream, and it can arise from any number of infectious bugs that attack the body, such as meningitis, pneumonia and infections of the skin or bladder, to name a few. The blood poisoning is caused not by the germs themselves, but by the body’s hyper-response to those germs, when it releases a barrage of chemicals that can lead to organ failure.

Those chemicals cause the body to go into shock, and patients have symptoms such as chills, fever, confusion, rapid heartbeat, headache and skin rashes.

The best shot patients have is for doctors to treat them early, ideally giving a patient antibiotics and fluids within the first hour that they show symptoms. Dr. Andre Kalil, an associate professor of medicine at the University of Nebraska Medical Center, said even in the best-case scenario, antibiotics don’t always help.

“Unfortunately even with the best antibiotics and supportive care, a third of these patients will die,” Kalil said. “We don’t have other drugs that actually can act in the body in response to the infection. We just don’t.”

That wasn’t always in the case. In 2001 when the U.S. Food and Drug Administration approved Xigris, made by the pharmaceutical company Eli Lilly, hopes were high that it would keep thousands of patients from dying. The company’s initial clinical trials of the drug showed that it reduced the chances of dying by 20 percent in patients at risk of developing sepsis.

But the drug’s initial performance was somewhat disappointing. Some patients benefited from the drug, others did not, and doctors had trouble defining which type of patient would benefit the most. The drug was also very expensive, so many hospitals put protocols in place that strictly limited when the drug could be given — usually when all other methods had failed.

Dr. Jonathan Janes, medical director of acute care for Eli Lilly, said the company was encouraged by studies of the drug in real-life clinical settings, which showed that it kept many patients alive.

“We felt encouraged by those results, they seemed to support that the drug worked,” Janes said. “Obviously, you need your clinical trial data, but these results were nice to have.”

But questions about the drug’s effectiveness and safety began to surface. Patients getting Xigris had a slightly increased risk of bleeding. Increasingly skeptical that the expensive drug was actually effective, European regulators asked Eli Lilly to conduct a second clinical trial. The results were the nail in Xigris’ coffin — the trial showed that the drug was little better than placebo. Based on those results, Eli Lilly voluntarily pulled the drug from the market in October 2011.

“This was the first drug specifically licensed for sepsis, which leaves us essentially with nothing now,” said Dr. Greg Martin, director of the medical and coronary intensive care units at Emory University.

Drug’s Withdrawal A Premature Decision, Some Say

But a new analysis, published Monday in the journal Lancet Infectious Diseases, throws into question whether or not Xigris should have been withdrawn at all. In it, Nebraska’s Kalil analyzed the results of more than two dozen studies of Xigris, most performed in the “real-world” of clinics and hospitals, trying to save patients with sepsis.

The results suggest that Xigris is effective after all. The study found that Xigris reduced patients’ risk of dying by 18 percent, similar to the results Eli Lilly had reported in its first study of the drug.

“I was expecting to see a very small effect, close to no effect. I was surprised when we saw these kinds of results,” Kalil said.

So should the drug be put back on the market? The answer is uncertain and, as far as Eli Lilly is concerned, unfeasible. Putting the drug back on the market would mean conducting another long, expensive clinical trial to clear regulatory hurdles. Janes said the company has no plans to do that, even in the face of evidence suggesting the drug’s effectiveness.

“We have to live with the results of our clinical trials,” Janes said. “It goes back to the point of deciding what the company is going to invest in.”

Although the drug would likely help hundreds of thousands of patients, it will likely never be as profitable as drugs that can help millions of patients with more common conditions, such as high blood pressure, diabetes or cancer.

And questions remain about whether the drug was ever truly helpful for patients. Doctors never really identified the type of patient who would benefit the most from Xigris. The new study suggests that perhaps only the sickest patients really improve after taking the drug. Trials of the drug in pediatric patients like Rory never succeeded.

Dr. Cliff Deutschman, a professor of anesthesiology and critical care at the University of Pennsylvania, said he was never really convinced that the drug was better than treating patients with antibiotics and fluids.

“Ultimately, it’s pretty hard to know what to make of the results of these studies,” he said.

Since Xigris was introduced and withdrawn, doctors and hospitals also seem to have gotten a little better at screening and stopping sepsis in its early stages. Programs like the Stop Sepsis campaign, a program started by the Greater New York Hospital Association, emphasize promoting awareness of the condition and the critical importance of getting care to patients in the first hours of their symptoms.

But many doctors say a drug like Xigris would be invaluable in saving the lives of hundreds of thousands of patients. Martin said he still believes Xigris could be that drug.

“There’s real potential that this drug has the ability to treat and cure people. But we don’t know who the drug works best in, and that’s probably where the interest was lost,” Martin said.

And for now, it seems that doctors will never know. Since Eli Lilly withdrew the drug from the market, it is no longer available even for research purposes.

Deutschman said the biggest blow is that given the Xigris’s failure and Eli Lilly’s experience, other pharmaceutical companies will be reluctant to spend the money to pursue any treatment for sepsis. For now, the scientific and regulatory bar for a drug is very high.

“There still may be groups of people that it [Xigris] does work on, but because the drug is no longer available we’ll never know. And that’s discouraging,” he said.

Vitamin C: A potential life-saving treatment for sepsis

Public release date: 17-Nov-2010

Physicians caring for patients with sepsis may soon have a new safe and cost-effective treatment for this life-threatening illness.  Research led by Dr. Karel Tyml and his colleagues at The University of Western Ontario and Lawson Health Research Institute have found that vitamin C can not only prevent the onset of sepsis, but can reverse the disease.

Sepsis is caused by a bacterial infection that can begin anywhere in your body.  Your immune system goes into overdrive, overwhelming normal processes in your blood. The result is that small blood clots form, blocking blood flow to vital organs. This can lead to organ failure. Babies, the elderly and those with weakened immune systems are most likely to get sepsis. But even healthy people can become deathly ill from the disease.

According to Dr. Tyml, a professor at Western’s Schulich School of Medicine & Dentistry, patients with severe sepsis have a high mortality rate, nearly 40 percent, because there is no effective treatment.

“There are many facets to sepsis, but the one we have focused on for the past 10 years is the plugging of capillaries,” says Dr. Tyml.  Plugged capillaries prevent oxygenation and the supply of life-supporting materials to your organ tissue and stop the removal of metabolic waste product.  Plugged capillaries are seen in organs of septic patients.  These organs may eventually fail, leading to multiple organ failure and death.  Dr. Tyml’s lab was the first to discover this plugging by using intravital microscopy, a technique Dr. Tyml pioneered in Canada.

According to Dr. Tyml’s most recent publication, oxidative stress and the activated blood clotting pathway are the major factors responsible for the capillary plugging in sepsis. Through his research, Dr. Tyml has discovered that a single bolus of vitamin C injected early at the time of induction of sepsis, prevents capillary plugging.  He has also found that a delayed bolus injection of vitamin C can reverse plugging by restoring blood flow in previously plugged capillaries.

“Our research in mice with sepsis has found that early as well as delayed injections of vitamin C improves chance of survival significantly,” explains Dr. Tyml.  “Furthermore, the beneficial effect of a single bolus injection of vitamin C is long lasting and prevents capillary plugging for up to 24 hours post-injection.”

Dr. Tyml and his colleagues are eager to find appropriate support to move this research from the bench to the bedside to see if these findings translate to patients with sepsis.

The potential benefit of this treatment is substantial.  “Vitamin C is cheap and safe. Previous studies have shown that it can be injected intravenously into patients with no side effects,” says Dr. Tyml.  “It has the potential to significantly improve the outcome of sepsis patients world-wide.  This could be especially beneficially in developing countries where sepsis is more common and expensive treatments are not affordable.”