Oxford University, July 21, 2021
Globally, coronary heart diseases (caused by narrowed arteries that supply the heart with blood) claim nearly nine million lives each year1, the largest of any disease, and present a huge burden to health systems. Until now, it has been unclear whether eating meat increases the risk of heart disease, and if this varies for different kinds of meat.
Researchers at the University of Oxford's Nuffield Department of Population Health have conducted the largest systematic review of the prospective evidence to date, including thirteen cohort studies involving over 1.4 million people. The study participants completed detailed dietary assessments, and their health was tracked for up to 30 years. The results are published today in Critical Reviews in Food Science and Nutrition.
Overall, the evidence from the analysis indicated that:
- Each 50 g/day higher intake of processed meat (e.g. bacon, ham, and sausages) increased the risk of coronary heart disease by 18%.
- Each 50 g/day higher intake of unprocessed red meat (such as beef, lamb and pork) increased the risk of coronary heart disease by 9%.
- There was no clear link between eating poultry (such as chicken and turkey) and an increased risk of coronary heart disease.
The findings may be because of the high content of saturated fat in red meat, and of sodium (salt) in processed meat. High intakes of saturated fat increase levels of harmful low-density lipoprotein (LDL) cholesterol, whilst excess salt consumption raises blood pressure. Both LDL cholesterol and high blood pressure are well-established risk factors for coronary heart disease.
Previous work from the same research team has also indicated that even moderate intakes of red and processed meat are associated with increased risk of bowel cancer2.
Dr. Keren Papier (Nuffield Department of Population Health), co-lead author of the study, said: "Red and processed meat have been consistently linked with bowel cancer and our findings suggest an additional role in heart disease. Therefore, current recommendations to limit red and processed meat consumption may also assist with the prevention of coronary heart disease."
Dr. Anika Knüppel, from the Nuffield Department of Population Health and the other co-lead author of the study, added: "We know that meat production is a major contributor to greenhouse gas emissions and we need to reduce meat production and thereby consumption to benefit the environment. Our study shows that a reduction in red and processed meat intake would bring personal health benefits too."
Currently in the UK, about 10 in 100 people would be expected to eventually die from coronary heart disease. Based on the findings from the present study and current red and processed meat intakes in the UK,4 if all these 100 people reduced their unprocessed red meat intake by three-quarters (for example from four times a week to one time a week), or if they stopped consuming processed meat altogether, deaths from coronary heart disease would decrease from 10 in 100 down to 9 in 100.
The studies involved in this analysis were mostly based on white adults living in Europe or the U.S.. The research team say more data are needed to examine these associations in other populations, including East Asia and Africa.
La Jolla Institute for Immunology and Emory University, July 22, 2021
You can't make a banana split without bananas. And you can't generate stable regulatory T cells without Vitamin C or enzymes called TET proteins, it appears.
Regulatory T cells (Tregs) help control inflammation and autoimmunity in the body. Tregs are so important, in fact, that scientists are working to generate stable induced Tregs (iTregs) in vitro for use as treatments for autoimmune diseases as well as rejection to transplanted organs. Unfortunately, it has proven difficult to find the right molecular ingredients to induce stable iTregs.
Now scientists at La Jolla Institute for Immunology and Emory University School of Medicine report that Vitamin C and TET proteins can work together to give Tregs their life-saving power.
"Vitamin C can be used to stabilize iTregs generated in vitro," says LJI Instructor Xiaojing Yue, Ph.D., who served as co-first author for the EMBO Reports study. "We hope that these kinds of induced Tregs can be used in the future for treatment of autoimmune diseases and organ transplantation."
The recent study, led by LJI Professor Anjana Rao, Ph.D., and Emory Instructor Benjamin G Barwick, Ph.D., builds on the previous discovery that Vitamin C can enhance the enzymatic activity of TET proteins and prompt the generation of stable iTregs under lab conditions.
This finding was encouraging, but the scientists did not want to work toward new autoimmune therapies without first analyzing the gene expression patterns and other key epigenetic features of the induced Tregs.
"We wanted to study the entire system at a whole genome level using next generation sequencing technology to better understand the molecular features of these cells," says Yue.
Study co-first author Daniela Samaniego-Castruita, a graduate student at LJI, spearheaded the analysis of gene expression and epigenetic changes in the iTregs. A major type of epigenetic modification involves the DNA itself through the addition or removal of molecules called methyl groups from cytosines, one of the four DNA bases. The methyl groups can be further oxidized by TET enzymes. All of these interactions can eventually change how cells "read" the DNA code.
Another type of epigenetic change involves the alteration of DNA accessibility: whether DNA is loosely or tightly coiled. As the DNA coils unwind, regulatory regions become exposed which subsequently influence gene expression.
In their analysis, the researchers found TET proteins are absolutely required for maintaining the gene expression and epigenetic features that make Tregs as what they are; and adding Vitamin C led to iTregs with similar similar gene expression and epigenetic features as normal "wild type" Tregs found in the body. The study also reveals an intriguing connection between TET enzymatic activity, Vitamin C and IL-2/STAT5 signaling.
"In mice that are deficient for components of IL-2/STAT5 signaling, such as IL-2, IL-2 receptors or STAT5, the Tregs cannot develop properly or they can have impaired function," Yue says.
The researchers demonstrate that on one hand, TET-deficiency in Treg cells leads to impaired IL-2/STAT5 signaling; on the other hand, Vitamin C confers iTregs enhanced IL-2/STAT5 signaling by increasing the expression level of IL-2 receptor and the functional form of STAT5, and STAT5 binding to essential regions in the genome, rendering these cells survive better in tough environments with low IL-2 supplementation.
"We are looking for more small molecules to stabilize TET activity and generate induced Tregs that are even more stable," says Yue. "These induced Tregs could eventually be used to treat patients."
"This research gives us a new way to think about treating autoimmune diseases," says Samaniego-Castruita.