One day coffee is good for you and the next day it’s bad. The nutrition news is filled with conflicting reports—about wine, chocolate, smoothies, gluten-free snacks, plant-based meat replacements, and more. It’s hard to know which foods can actually help fend off disease and promote better health.
As Michael Pollan wrote in his book In Defense of Food, “Nutrition science is where surgery was about 1650 … really interesting and promising, but would you want to have them operate on you yet? I don’t think so.”
The relationship between food and health is mind-bogglingly complex: The more we discover, the more we need to know. Einstein researchers are trying to make sense of nutrition from a host of different angles. Here’s a sampling of their work.
Decades ago, epidemiologists established that the Western diet—featuring high consumption of red and processed meats, added sugar, and refined grains—is a major contributor to colorectal cancer, increasing its incidence almost tenfold compared with populations consuming non-Western diets. More recently, there has been an alarming increase in colorectal cancer cases among younger Gen Xers and millennials, with diet considered the major driver. But what, physiologically speaking, is causing this cancer, and can anything be done about it?
It has long been thought that the Western diet causes colorectal cancer by mutating the stem cells principally responsible for producing all other intestinal cells. But in recent years, scientists have demonstrated that a large spectrum of intestinal cells can function as “alternate” stem cells.
Researchers led by Len Augenlicht, Ph.D., professor of oncology, of medicine, and of cell biology at Einstein, have shown that the Western diet actually suppresses the activity of those stem cells considered mainly responsible for producing all the other intestinal cells—while, at the same time, the Western diet recruits certain intestinal cells to become alternate stem cells.
Some of those alternate intestinal stem cells harbor mutations and other changes that cause them to develop into cancerous intestinal cells. Different dietary exposures cause rapid changes in the alternate stem cells daily, resulting in colorectal cancer if the “wrong” stem cells prevail. “Most notably,” Dr. Augenlicht says, “our research shows that cells derived from mutated alternate stem cells stimulate an inflammatory response—a major factor in causing them to develop into tumors.”
In recent papers in Nature Genetics, Molecular Cancer Research, and Aging Cell, Dr. Augenlicht and his colleague Jiahn Choi, Ph.D., an instructor in Einstein’s cell biology department, have described the complex mechanisms by which the Western diet encourages the development of defective alternate stem cells that eventually cause colorectal tumors. Those papers report parallels between the inflammation that fuels colorectal cancer and the inflammation characterizing inflammatory bowel disease and aging, both of which are also risk factors for tumor development.
The good news from the Einstein studies is that many of the harmful intestinal changes wrought by the Western diet are quickly reversible. “The intestinal environment is highly dynamic,” says Dr. Augenlicht, whose research is funded by the National Institutes of Health (NIH). “Your gut today is not what it was yesterday or will be tomorrow. It depends upon what you eat. The gut is always adapting, and that includes the programming and functioning of different stem cell populations.”
Which is another way of saying that it’s never too late for people to improve their diets and lower their cancer risk, says the researcher.
Dr. Augenlicht stresses the importance of regular colonoscopies. “We know that screening is extremely effective at preventing colorectal cancer,” he says. “But I think we can make screening, prevention, and treatment even better. The goal is to biopsy suspicious growths and then, based on the molecular changes that we see in intestinal stem cells, recommend to patients how often they should be screened and how they should be treated.”
Len Augenlicht, Ph.D., professor of oncology, of medicine, and of cell biology at Einstein
It has been known for centuries that different parts of the body harbor different microbes. But only recently have scientists realized that the body’s resident collection of bacteria and viruses—now known as the microbiome—influences our health.
Most of these microbes live in the gut, and studies are now implicating imbalances in intestinal flora in everything from heart disease to stroke to obesity to ulcerative colitis. These studies have generally found that unhealthy diets lead to microbiomes that lack diversity, which in turn are associated with increased risk for poor health. Researchers have also identified certain bacterial species that are associated with good health—and others that are associated with disease.
One recent study, published in June 2024 in Nature Medicine and co-authored by several Einstein researchers, suggests that changes in the gut microbiome precede the development of type 2 diabetes—a discovery that could lead to entirely new therapies for preventing or treating this all-too-common chronic disease. The study, the largest and most comprehensive of its kind, characterized the microbiomes of more than 8,000 individuals, including those with type 2 diabetes, prediabetes, or normal blood-glucose levels.
“We found that 19 different species of bacteria were closely associated with type 2 diabetes,” says study co-author Qibin Qi, Ph.D., professor of epidemiology & population health, associate director of the department of epidemiology & population health’s Center for Population Cohorts at Einstein, and a member of the National Cancer Institute–designated Montefiore Einstein Comprehensive Cancer Center. The study also linked different species of microbes with varying levels of type 2 diabetes risk.
The study doesn’t explain why these microbes are associated with diabetes, but it’s a critical first step toward understanding a previously unappreciated contributor to the disease. The findings could lead to biomarkers for predicting a patient’s risk for type 2 diabetes, and to therapies, such as probiotics, fecal transplants, or drugs, aimed at treating or even preventing type 2 diabetes by inhibiting harmful microbes and promoting helpful ones.
“This and other studies tell us that we need to look at the microbiome as an endocrine organ capable of secreting substances that contribute to metabolic health, much as the liver, pituitary gland, and pancreas do,” adds Dr. Qi.
In another diet study, Dr. Qi looked at data from more than 11,000 participants in the Hispanic Community Health Study/Study of Latinos, for which Einstein is one of four national sites. The researchers found that higher fiber intake was associated with specific “good” bacterial species in the participants’ gut microbiome, and that serum metabolites produced by those bacteria have anti-inflammatory and antioxidant properties and improve glucose metabolism. The findings were published online in March 2024 in Circulation Research, a journal of the American Heart Association.
Those gut microbes and metabolites were associated with a lower risk of developing type 2 diabetes during an average follow-up period of six years. Knowing which bacteria and metabolites are linked to higher fiber intake and lower risk for type 2 diabetes could lead to personalized diets and other therapeutic strategies for people at risk for the disease.
Qibin Qi, Ph.D., professor of epidemiology & population health, associate director of the Center for Population Cohorts at Einstein, and a member of Montefiore Einstein Comprehensive Cancer Center
During her Einstein research career, nutrition expert Yasmin Mossavar-Rahmani, Ph.D., R.D., professor of epidemiology & population health, has been involved in several cohort studies examining associations between diet and health. For example, a study she led on postmenopausal women enrolled in the Women’s Health Initiative found that drinking two or more artificially sweetened beverages daily is associated with an increased risk of stroke, coronary heart disease, and death from all causes. She has also participated in studies concluding that drinking one or more sugar-sweetened beverages daily is linked to an increased risk for liver cancer and death from liver cancer, and that a high potassium intake among postmenopausal women is associated with a lower risk of stroke and death from all causes.
Most recently, she has been investigating whether an anti-inflammatory diet called the Multicultural Healthy Diet can reduce cognitive decline and Alzheimer’s disease risk. Her study—a randomized, controlled phase 2 pilot trial—examined the effects of that diet on brain health in a multicultural population in the Bronx. Those enrolled were adults ages 40 to 65.
As is true for the well-known Mediterranean diet, the anti-inflammatory Multicultural Healthy Diet is rich in fruits, vegetables, fish, and whole grains. Additionally, it is designed to emphasize adequate hydration and the use of spices and herbs. By reducing chronic inflammation and oxidative stress in the body, anti-inflammatory diets have been associated with lower risk of heart disease, diabetes, and cancer. But whether such diets can also bolster cognitive health and slow the onset of Alzheimer’s disease has yet to be determined.
Yasmin Mossavar-Rahmani, Ph.D., R.D., professor of epidemiology & population health
The Multicultural Healthy Diet trial follows findings from a study of the MIND diet (short for the Mediterranean-DASH Intervention for Neurodegenerative Delay) published in 2023 in the New England Journal of Medicine. This three-year randomized, controlled trial found no difference in cognitive status in participants who followed the MIND diet versus participants who did not follow the diet. Participants were cognitively normal adults with family histories of dementia.
“The MIND diet trial enrolled people over 65,” says Dr. Mossavar-Rahmani. “At that age, it may be too late to slow the development of dementia. In contrast, we’re looking at adults between 40 and 65 years of age, perhaps before the processes that lead to Alzheimer’s disease have had a chance to take hold. We still don’t know the best time to start a diet intervention and how long it should last to have an impact.”
Her recently concluded Multicultural Healthy Diet trial, funded by the NIH, was designed to coach participants on how to incorporate the diet into their usual cuisine—a task complicated by the pandemic. In-person group meetings for introducing participants to new foods and spices were replaced by Zoom meetings, and limited local supplies of fruits and vegetables during the pandemic made dietary changes difficult.
Five times each day throughout the study, participants were asked to play brain games on their smartphones that measured visual and spatial memory, processing speed, short- and long-term memory, and working memory capacity. The researchers also evaluated the participants’ blood for changes in folate, tocopherols, carotenoids, vitamin B12, fatty acids, and other biomarkers of brain health.
The study’s 290 generally healthy participants were followed for a period of nine months. “That may not be long enough to detect any change in the onset of Alzheimer’s disease,” acknowledges Dr. Mossavar-Rahmani, who is now analyzing data from the study. “But maybe the dietary changes can push biomarkers of cognitive health in the right direction. If results from the phase 2 trial are promising, they have the potential to inform the design and goals of a future phase 3 trial.”
Until a decade or so ago, the liver was thought to quietly conduct its business, receiving the brain’s instructions about metabolizing nutrients, detoxifying substances such as drugs and alcohol, storing or releasing energy-rich glycogen, and more. But the liver turns out to be quite the chatterbox, engaging in a constant dialogue with the brain—particularly the hypothalamus, the brain structure that regulates hunger, blood pressure, mood, and sleep, among other vital functions.
The conversations between the liver and the hypothalamus and what is discussed in them are now being interpreted, thanks in part to studies by Young-Hwan Jo, Ph.D., professor of medicine, of molecular pharmacology, and in the Dominick P. Purpura Department of Neuroscience at Einstein.
Research by Dr. Jo and others points to the vagus nerve as a vital link between the hypothalamus and the liver. The vagus nerve is one of the longest and most complex nerves in the human body, with links to many organs. Complicating matters are the many bundles of vagal nerves that connect to the liver, with each bundle seemingly having a different function.
In a mouse study published in 2020 in Nature Communications, Dr. Jo found a novel pathway between the brain and liver that involves vagal motor neurons. This connection enables communication between the liver and a specific region of the hypothalamus that regulates food intake and maintains energy balance.
“Our studies show that the liver and the hypothalamus use this connection to balance blood glucose levels,” says Dr. Jo. “Importantly, this mechanism appears to work independently of the pancreas and its secretion of insulin, which means that we may have found a new way to treat diabetes and obesity and control appetite.”
In another intriguing line of research, Dr. Jo is investigating the role of liver-brain connections in causing psychological problems. “It’s known that people with a condition known as metabolic dysfunction–associated steatotic liver disease (MASLD), characterized by excess fat in the liver, have a higher risk of psychiatric disorders such as anxiety and depression, suggesting that impaired hepatic lipid metabolism may be closely associated with mental illness,” he says. “We suspect that MASLD has disrupted the brain’s ability to sense the signaling molecules sent to it by the vagal sensory nerves that innervate the liver, resulting in those psychiatric disorders.”
Dr. Jo hopes to discover the vagal sensory neurons involved in communications between the liver and the brain and whether their function is impaired in patients with MASLD. “Our studies may show that signaling molecules secreted by the liver also dictate the messages that liver-innervating vagal neurons send to the brain, thereby influencing energy balance and mental health,” he says.
Young-Hwan Jo, Ph.D., professor of medicine, of molecular pharmacology, and in the Dominick P. Purpura Department of Neuroscience at Einstein
