Two contrasting research reports on eating high-fat food
By Will Collette
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I pay attention to the latest research and often re-run
journal summaries of interesting new research in Progressive Charlestown. With
so much bullshit being spewed by Robert F. Kennedy Jr. about health and
nutrition, heeding the findings of real scientific research is becoming a
necessity for anyone who wants to live a long and healthy life.
I was somewhat surprised to see two journal reports come out
within a day of each other (December 21 and 22) addressing the health effects
of high-fats diets. Putting aside Bobby Jr.’s advice to use tallow or lard for
cooking instead of most cooking oils, these reports convey two very different
signals about the connection between what we eat and our health.
On December 21, the American Academy of Neurology released a
report showing a correlation between eating high-fat dairy products and a
lowered risk of dementia. They caution that a correlation (a statistical
analysis) is not the same as finding there is cause and effect.
The next day, December 22, MIT released a report that looked
at how high-fat diets cause physical changes in the liver. As they bluntly put
it:
Eating a diet high in fat is one of the strongest known risk factors for liver cancer. New research from MIT explains why, showing that fatty diets can fundamentally change how liver cells behave in ways that make cancer more likely to develop.
During the holidays, we tend to cast away all restraints on
what we eat. But come January, the bill for the debts we accumulate during the
holiday season come due.
I have reprinted the research summaries for both research studies below.
MIT Reveals How High-Fat Diets Quietly Prime the Liver
for Cancer
By Massachusetts Institute
of Technology
A fatty diet doesn’t just damage the liver — it rewires
its cells in ways that give cancer a dangerous head start.
Eating a diet high in fat is one of the strongest known risk
factors for liver cancer. New research from MIT explains why, showing
that fatty diets can fundamentally change how liver cells behave in ways that
make cancer more likely to develop.
The study found that when the liver is exposed to a high-fat
diet, mature liver cells called hepatocytes undergo a striking shift. Instead
of maintaining their specialized roles, these cells revert to a more primitive,
stem-cell-like state. While this transformation helps the cells cope with the
ongoing stress caused by excess fat, it also leaves them far more vulnerable to
becoming cancerous over time.
“If cells are forced to deal with a stressor, such as a
high-fat diet, over and over again, they will do things that will help them
survive, but at the risk of increased susceptibility to tumorigenesis,” says
Alex K. Shalek, director of the Institute for Medical Engineering and Sciences
(IMES), the J. W. Kieckhefer Professor in IMES and the Department of Chemistry,
and a member of the Koch Institute for Integrative Cancer Research at MIT, the
Ragon Institute of MGH, MIT, and Harvard, and the Broad Institute of MIT and
Harvard.
The team also pinpointed several transcription factors that
appear to drive this cellular regression. Because these molecules help control
whether liver cells stay mature or revert to an immature state, they may offer
promising targets for future drugs aimed at reducing cancer risk in vulnerable
patients.
Shalek; Ömer Yilmaz, an MIT associate professor of biology
and a member of the Koch Institute; and Wolfram Goessling, co-director of the
Harvard-MIT Program in Health Sciences and Technology, are the senior authors
of the study, which appears today in Cell. MIT graduate student Constantine
Tzouanas, former MIT postdoc Jessica Shay, and Massachusetts General Brigham
postdoc Marc Sherman are the co-first authors of the paper.
What Happens to Liver Cells Under Long-Term Fat Stress
High-fat diets are known to promote inflammation and fat
buildup in the liver, leading to a condition called steatotic liver disease.
This disorder can also result from other long-term metabolic stresses,
including heavy alcohol use, and may progress to cirrhosis, liver failure, and
eventually cancer.
To better understand what drives this progression, the
researchers focused on how liver cells respond at the genetic level when
exposed to a high-fat diet, especially which genes are activated or shut down
as damage accumulates over time.
The team fed mice a high-fat diet and used single-cell
RNA-sequencing to analyze liver cells at multiple stages of disease
development. This approach allowed them to track changes in gene activity as
the animals moved from early inflammation to tissue scarring and, ultimately,
liver cancer.
Early in the process, hepatocytes began activating genes
that promote survival under stress. These included genes that reduce the
likelihood of cell death and encourage continued cell division. At the same
time, genes essential for normal liver function, such as those involved in
metabolism and protein secretion, were gradually switched off.
“This really looks like a trade-off, prioritizing what’s
good for the individual cell to stay alive in a stressful environment, at the
expense of what the collective tissue should be doing,” Tzouanas says.
Some of these shifts occurred quickly, while others
developed more slowly. In particular, the decline in metabolic enzyme
production unfolded over a longer period. By the end of the study, nearly all
mice on the high-fat diet had developed liver cancer.
Why Immature Cells Are More Vulnerable to Cancer
According to the researchers, liver cells that revert to a
less mature state appear to be especially susceptible to cancer if they later
acquire harmful mutations.
“These cells have already turned on the same genes that
they’re going to need to become cancerous. They’ve already shifted away from
the mature identity that would otherwise drag down their ability to
proliferate,” Tzouanas says. “Once a cell picks up the wrong mutation, then
it’s really off to the races and they’ve already gotten a head start on some of
those hallmarks of cancer.”
The team also identified specific genes that help coordinate
this shift back to an immature state. During the course of the study, a drug
targeting one of these genes (thyroid hormone receptor) was approved to treat a
severe form of steatotic liver disease known as MASH fibrosis. In addition, a
drug that activates another enzyme highlighted in the research (HMGCS2) is
currently being tested in clinical trials for steatotic liver disease.
Another potential drug target identified by the researchers
is a transcription factor called SOX4. This factor is typically active during
fetal development and in only a limited number of adult tissues (but not the
liver), making its reactivation in liver cells particularly notable.
Evidence From Human Liver Disease
After observing these effects in mice, the researchers
examined whether the same patterns could be found in people. They analyzed
liver tissue samples from patients at various stages of liver disease,
including individuals who had not yet developed cancer.
The human data closely matched the findings in mice. Over
time, genes required for healthy liver function declined, while genes linked to
immature cell states became more active. Using these gene expression patterns,
the researchers were also able to predict patient survival outcomes.
“Patients who had higher expression of these
pro-cell-survival genes that are turned on with high-fat diet survived for less
time after tumors developed,” Tzouanas says. “And if a patient has lower
expression of genes that support the functions that the liver normally
performs, they also survive for less time.”
While cancer developed within about a year in mice, the
researchers believe the same process unfolds much more slowly in humans,
potentially over a span of roughly 20 years. The timeline likely varies
depending on factors such as diet, alcohol use, and viral infections, all of
which can encourage liver cells to revert to an immature state.
Can the Damage Be Reversed?
The researchers now plan to explore whether the cellular
changes triggered by a high-fat diet can be reversed. Future studies will test
whether returning to a healthier diet or using weight-loss medications such as
GLP-1 agonists can restore normal liver cell function.
They also hope to further evaluate the transcription factors
identified in the study as possible drug targets to prevent damaged liver
tissue from progressing to cancer.
“We now have all these new molecular targets and a better
understanding of what is underlying the biology, which could give us new angles
to improve outcomes for patients,” Shalek says.
Reference: “Hepatic adaptation to chronic metabolic stress
primes tumorigenesis” 22 December 2025, Cell.
DOI: 10.1016/j.cell.2025.11.031
The research was funded, in part, by a Fannie and John Hertz
Foundation Fellowship, a National Science Foundation Graduate Research
Fellowship, the National Institutes of Health, and the MIT Stem Cell
Initiative through Foundation MIT.
Study links full-fat cheese to lower dementia risk
Full-fat cheese and cream may have an unexpected link to
better brain health.
American Academy of Neurology
Highlights:
- A
large new study suggests that eating more full-fat cheese and cream may be
linked to a lower risk of developing dementia later in life.
- High-fat
cheeses are defined as containing more than 20% fat and include familiar
varieties such as cheddar, Brie and Gouda.
- Participants
who ate 50 grams or more of high-fat cheese each day had a 13% lower risk
of dementia compared with those who ate less than 15 grams daily.
- People
who consumed at least 20 grams of high-fat cream per day also showed a
reduced dementia risk, about 16% lower than those who did not consume
cream.
- Researchers
found no similar link for low-fat cheese, low-fat cream, milk, butter or
fermented milk products.
- Scientists
emphasize that more research is needed to confirm these findings and to
better understand whether certain high-fat dairy foods could help support
brain health.
Full-Fat Dairy and Dementia Risk
People who eat higher amounts of full-fat cheese and cream
may be less likely to develop dementia later in life, according to a new study
published on December 17, 2025, in Neurology, the medical journal of the
American Academy of Neurology. The findings point to a connection between these
foods and dementia risk, but they do not prove that eating high-fat dairy
prevents dementia. Instead, the study identifies an association.
High-fat cheeses are defined as having more than 20% fat and
include common types such as cheddar, Brie and Gouda. High-fat creams generally
contain 30-40% fat and include whipping cream, double cream and clotted cream.
In grocery stores, these products are often sold as "full-fat" or
"regular" options.
"For decades, the debate over high-fat versus low-fat
diets has shaped health advice, sometimes even categorizing cheese as an
unhealthy food to limit," said Emily Sonestedt, PhD, of Lund University,
Sweden "Our study found that some high-fat dairy products may actually
lower the risk of dementia, challenging some long-held assumptions about fat
and brain health."
How the Study Followed Participants Over Time
The research team analyzed dietary and health data from
27,670 adults in Sweden. At the beginning of the study, participants were an
average of 58 years old. They were followed for about 25 years, during which
time 3,208 people were diagnosed with dementia.
To track eating habits, participants recorded everything
they consumed over the course of one week. They also answered questions about
how frequently they ate specific foods during the previous several years and
discussed their food preparation methods with researchers.
Cheese Intake and Dementia Outcomes
One part of the analysis focused on daily consumption of
high-fat cheese. Researchers compared people who ate 50 grams or more per day
with those who ate less than 15 grams per day. Fifty grams of cheese is roughly
equal to two slices of cheddar or about half a cup of shredded cheese and is
approximately 1.8 ounces. A typical serving of cheese is one ounce.
By the end of the study period, 10% of participants who ate
higher amounts of high-fat cheese had developed dementia, compared with 13% of
those who ate less. After accounting for differences in age, sex, education and
overall diet quality, the researchers found that higher cheese consumption was
associated with a 13% lower risk of dementia.
When specific forms of dementia were examined, the
association was strongest for vascular dementia. People who consumed more
high-fat cheese had a 29% lower risk of developing this type.
The researchers also observed a lower risk of Alzheimer's
disease among participants who ate more high-fat cheese, but this pattern was
only seen in those who did not carry the APOE e4 gene variant -- a genetic risk
factor for Alzheimer's disease.
High-Fat Cream and Dementia Risk
The study also looked at consumption of high-fat cream.
Researchers compared people who consumed 20 grams or more per day with those
who did not consume any. Twenty grams of high-fat cream is about 1.4
tablespoons of heavy whipping cream. A recommended serving is about 1-2
tablespoons.
After making similar adjustments for health and lifestyle
factors, the researchers found that daily consumption of high-fat cream was
linked to a 16% lower risk of dementia compared with consuming none.
Differences Among Dairy Products
Not all dairy foods showed the same relationship with
dementia risk. The researchers found no association between dementia and
consumption of low-fat cheese, low-fat cream, high- or low-fat milk, butter or
fermented milk, which includes yogurt, kefir and buttermilk.
"These findings suggest that when it comes to brain
health not all dairy is equal," said Sonestedt. "While eating more
high-fat cheese and cream was linked to a reduced risk of dementia, other dairy
products and low-fat alternatives did not show the same effect. More research
is needed to confirm our study results and further explore whether consuming
certain high-fat dairy truly offers some level of protection for the
brain."
Study Limitations and Future Research
One limitation of the study is that all participants lived
in Sweden, which means the results may not apply to people in other countries.
Sonestedt noted that dietary habits differ between regions. In Sweden, cheese
is often eaten uncooked, while in the United States, cheese is frequently
heated or eaten alongside meat. Because of these differences, she emphasized
that similar studies should also be carried out in the United States.
The study was supported by Swedish Research Council, Swedish
Heart and Lung Foundation, Crafoord Foundation, Magnus Bergvall Foundation and
Albert Påhlsson Foundation.
Journal Reference:
- Yufeng
Du, Yan Borné, Jessica Samuelsson, Isabelle Glans, Xiaobin Hu, Katarina
Nägga, Sebastian Palmqvist, Oskar Hansson, Emily Sonestedt. High-
and Low-Fat Dairy Consumption and Long-Term Risk of Dementia. Neurology,
2026; 106 (2) DOI: 10.1212/WNL.0000000000214343
