Vitamin C may boost effectiveness of acute myeloid leukemia treatment

Date: August 29, 2016

Source: Van Andel Research Institute

Summary:

A simple adjustment to patients' therapeutic regimen may improve the effectiveness of the standard epigenetic treatment for myeloid dysplastic syndrome (MDS) and acute myeloid leukemia (AML).

A simple adjustment to patients' therapeutic regimen may improve the effectiveness of the standard epigenetic treatment for myeloid dysplastic syndrome (MDS) and acute myeloid leukemia (AML).

New findings published in the Proceedings of the National Academy of Sciences showed in lab studies that supplementing an epigenetic cancer drug called decitabine with vitamin C enhanced the drug's ability to impede cancer cell growth and trigger cellular self-destruction in cancer cell lines. A pilot clinical trial based on this work is ongoing in adult patients with MDS or AML at Rigshospitalet in Copenhagen, Denmark. It combines a similar drug called azacitidine -- the standard of care therapy -- with vitamin C. Many cancer patients are deficient in vitamin C; the proposed approach seeks to correct this deficiency rather than overload patients with the vitamin.

"If the pilot trial is successful, we plan to pursue a larger trial to explore this strategy's potential as a straightforward and cost-effective way to improve the existing therapy for AML and MDS," said Peter Jones, Ph.D., D.Sc., co-senior author of the PNAS study, chief scientific officer at Van Andel Research Institute (VARI) and co-leader of the Van Andel Research Institute-Stand Up To Cancer (VARI-SU2C) Epigenetics Dream Team. "At the same time, we must urge patience and caution. Only a clinical trial that combines azacitidine with the blinded addition of either vitamin C or a placebo will give the true answer as to whether or not vitamin C increases the efficacy of azacitidine in patients. We must emphasize that our trial is limited to a certain subset of patients with MDS or AML on a specific therapeutic regimen. We do not have evidence that this approach is appropriate for other cancers or chemotherapies."

The proposed strategy reflects a continuing move toward combination therapies, particularly when it comes to epigenetic approaches, which target the mechanisms that control whether genes are switched "on" or "off." In cancer, these switches inappropriately activate or silence important genes, such as those that regulate cell growth and life cycle, ultimately leading to tumors. Epigenetic therapies are thought to work in two ways to fix these errors in cancer cells -- by correcting the "position" of the gene switches and by making the cell appear as though it's infected by a virus, triggering the immune system.

The trial is led by Kirsten Grønbæk, M.D., DMSc., chief hematologist and professor at University of Copenhagen's Rigshospitalet and member of the VARI-SU2C Epigenetics Dream Team, which is supporting the trial and associated research. It will include 20 patients; preliminary results are expected by spring or summer 2017.

"This type of combination therapy is promising but more work is needed to determine its safety and efficacy," Grønbæk said. "It is truly exciting to consider that there could be a simple and elegant approach to help patients fight MDS and AML. However, as a physician, I strongly urge patients to wait for the results of the clinical trial and to discuss all dietary and supplemental changes with their doctors."

An estimated 13,000 people in the U.S. are diagnosed with MDS annually and about 20,000 are diagnosed with AML. Currently, only about half of patients with MDS and AML respond to the epigenetic therapy alone.

Story Source:

The above post is reprinted from materials provided by Van Andel Research Institute. Note: Content may be edited for style and length.

Journal Reference:

Minmin Liu, Hitoshi Ohtani, Wanding Zhou, Andreas Due Ørskov, Jessica Charlet, Yang W. Zhang, Hui Shen, Stephen B. Baylin, Gangning Liang, Kirsten Grønbæk, Peter A. Jones. Vitamin C increases viral mimicry induced by 5-aza-2′-deoxycytidine. Proceedings of the National Academy of Sciences, 2016; 201612262 DOI:10.1073/pnas.1612262113

Cite This Page:

Van Andel Research Institute. "Vitamin C may boost effectiveness of acute myeloid leukemia treatment." ScienceDaily. ScienceDaily, 29 August 2016. <www.sciencedaily.com/releases/2016/08/160829192647.htm>.

Folic acid fortified food linked to decline in congenital heart defects

Date: August 29, 2016

Source: American Heart Association

Summary:

Food fortified with folic acid helped lower overall rates of congenital heart defects in Canada. The effect was evident in some types of congenital heart defects but not all.

Food fortified with folic acid, a B vitamin required in human diets for numerous biological functions, was associated with reduced rates of congenital heart defects, according to new research in the American Heart Association's journalCirculation.

"Our study examined the effect of folic acid food fortification on each specific subtype of congenital heart disease based on the Canadian experience before and after food fortification was made mandatory in 1998," said K.S. Joseph, M.D., Ph.D., the study's senior author and professor in the Department of Obstetrics and Gynecology and the School of Population and Public Health at the University of British Columbia in Vancouver, Canada.

Controlling for influences such as maternal age, multiple births (twins, triplets), pregnancy complications, prenatal diagnosis and pregnancy terminations, researchers analyzed data from nearly 6 million Canadian births from 1990 to 2011 and found that folic acid food fortification was associated with an 11 percent reduction in rates of congenital heart defects overall.

They also found that the beneficial effects of folic acid were evident in some subtypes of congenital heart defects but not others, such as a:

27 percent reduction in conotruncal defects, or severe heart outflow tract abnormalities; 23 percent reduction in coarctation of the aorta -- a narrowing of the major artery (the aorta) that carries blood to the body; 15 percent reduction in atrial and ventricular septal defects -- holes in the wall separating heart chambers; however, no changes were seen with regard to chromosomally associated defects -- abnormality in the number of an infant's chromosomes.

Canada mandated adding folic acid to all types of flour, enriched pasta and cornmeal, primarily aimed at preventing neural tube defects in 1998. The study's findings are applicable to the U.S. population because food fortification with folic acid was implemented at approximately the same time and levels in the U.S. as Canada because of the North American Fair Trade Agreement of 1994, Joseph said.

Folic acid is especially important for rapid cell division and growth, for instance, when blood is being formed and in pregnancy when the fetus is growing rapidly. Folate deficiency can result in several different complications -- the most important of these are neural tube defects (such as spina bifida, an abnormality of the spine and spinal cord) in babies and anemia (in which the number and function of red blood cells is affected leading to an inability of the blood to carry sufficient oxygen).

Joseph added that women who are likely to get pregnant should start taking folic acid supplements before getting pregnant as they may not necessarily receive adequate folate from diet alone.

It is estimated that there are about 650,000 to 1.3 million children and adults living with congenital heart disease in the United States. Ventricular septal defects are the most common type of defect in children and account for nearly 620,000 of the cases.

Story Source:

The above post is reprinted from materials provided by American Heart Association. Note: Content may be edited for style and length.

Journal Reference:

Shiliang Liu, K.S. Joseph, Wei Luo, Juan Andrés León, Sarka Lisonkova, Michiel Van den Hof, Jane Evans, Ken Lim, Julian Little, Reg Sauve, Michael S. Kramer. Effect of Folic Acid Food Fortification in Canada on Congenital Heart Disease SubtypesClinical Perspective.Circulation, 2016; 134 (9): 647 DOI:10.1161/CIRCULATIONAHA.116.022126

Cite This Page:

American Heart Association. "Folic acid fortified food linked to decline in congenital heart defects." ScienceDaily. ScienceDaily, 29 August 2016. <www.sciencedaily.com/releases/2016/08/160829192639.htm>.