Is It Time to Scrap Ultraprocessed Foods?

Ultraprocessed foods (UPFs) make up nearly three quarters of the entire US food supply and about 60% of Americans' daily caloric intake. A significant body of research has tied consumption of these foods — awash in added sugar, salt, fat, artificial colors, or preservatives — to cancer, diabetes, and heart disease.

Now, a growing number of studies also link them to poor brain health, including an increased risk of dementia, depression, and anxiety, and some experts are calling for public health policies aimed at reducing UPF consumption.

But what's the science behind the link between UPFs and brain health and what does it mean for clinicians and their patients?

Under Scrutiny

A mainstay of diets in countries around the world, UPFs have come under increasing scrutiny because of their link to major diseases. The ingredients in UPFs add little or no nutritional value. Their primary function is to increase a product's shelf life and platability. Some recent evidence suggests these foods may be as addictive as tobacco. In addition, two pooled analysis studies using the Yale Food Addiction Scale showed that 14% of adults and 12% of children in the US may have a UPF addiction.

The most widely used measure of what is, and what is not, a UPF was developed in 2009 by researchers in Brazil. The NOVA food classification system assigns food and beverages to one of four groups:

Unprocessed and minimally processed foods, such as fruits, vegetables, milk, and meat
Processed culinary ingredients, including white sugar, butter, and oils derived from seeds, nuts, and fruits
Processed foods, such as tomato paste, bacon, canned tuna, and wine
Ultraprocessed foods, such as soda, ice cream, breakfast cereal, and prepackaged meals

Those sounding the alarm about the potential harmful effects of UPFs are particularly concerned about their consumption by young people. The National Health and Nutrition Examination Survey showed that from 1999 to 2018, highly processed foods accounted for the majority of energy intake in those aged 2–19 years.

One of the most commonly used additives in UPFs, the artificial sweetener aspartame, garnered headlines this summer when the World Health Organization (WHO) classified it as a likely carcinogen in humans. Aspartame is used in thousands of products, from soda to chewing gum to chewable vitamins.

The US Food and Drug Administration (FDA) strongly disagreed with the WHO's position and is sticking by its recommended daily limit of 50 mg/kg of body weight — equivalent to 75 packets of the sweetener Equal — as safe for human consumption.

"Aspartame is one of the most studied food additives in the human food supply," FDA officials said in a statement, adding that the agency found "significant shortcomings" in the studies the WHO used to justify the new classification. "FDA scientists do not have safety concerns when aspartame is used under the approved conditions."

Increased attention to consumption of UPFs in general and aspartame particularly in recent years has yielded several studies pointing to the foods' association with compromised brain health.

Link to Depression, Dementia

A recent report on UPF consumption and mental well-being among nearly 300,000 people across 70 countries showed that 53% of those who consumed UPFs several times a day were distressed or were struggling with their mental well-being compared to 18% of those who rarely or never consumed UPFs.

Part of the Global Mind Project run by the nonprofit Sapien Labs in Arlington, Virginia, the report also showed that individuals with the highest rates of UPF consumption reported higher levels of confusion, slowed thinking, unwanted or obsessive thoughts, irritability, and feelings of sadness.

"There seems to be a much broader effect than just depression symptoms," Tara Thiagarajan, PhD, founder and chief scientist of Sapien Labs and co-author of the report, told Medscape Medical News.

The report, which has not been peer reviewed, comes on the heels of several other studies, including one from the Nurses Health Study II that showed that participants who consumed more than eight servings of UPFs daily had about a 50% higher depression risk compared to those who consumed half that much.

"We found that UPFs in general, and artificial sweeteners and beverages in particular, were associated with increased risk," said lead investigator Andrew T. Chan, MD, MPH, professor of medicine at Harvard Medical School and chief of the Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston.

"This was an interesting finding that correlates with data from animal studies that artificial sweeteners may trigger the transmission of particular signaling molecules in the brain that are important for mood," he told Medscape Medical News.

Cognition may also be affected. An analysis of more than 72,000 people in the UK Biobank showed that those who consumed a high levels of UPFs were 50% more likely to develop dementia than those who consumed fewer processed foods. For every 10% increase in UPF consumption, the odds of developing any kind of dementia increased by 25%.

Another study of nearly 11,000 people showed that higher UPF consumption was associated with a significantly faster decline in executive and global cognitive function.

Epigenetic Changes

While these and other studies suggest a link between UPF consumption and brain health, they are designed to demonstrate correlation. To date, no human study has proven that eating highly processed foods directly causes a decline in mental health or cognition.

Animal studies could provide that causal link. Earlier this year, researchers at Florida State University (FSU) in Tallahassee reported learning and memory deficits in two groups of male mice that completed a maze test after being fed water mixed with aspartame for about 20% of their adult lives compared to a group of mice that drank water only. Animals that ingested aspartame could finish the test, but it took them longer, and they needed help.

The amount of aspartame used in the study was just 7% and 15% of the FDA's recommended maximum intake of aspartame (equivalent to two to four 8-ounce diet sodas daily).

Most intriguing was that offspring of the mice in the aspartame groups demonstrated the same levels of cognitive decline and anxiety as their fathers, even though they had never ingested the artificial sweetener. Researchers theorize that in addition to changes in brain gene expression, aspartame also caused epigenetic changes in germ cells.

"Epigenetic changes in germ cells due to environmental exposures are both good and bad," lead investigator Pradeep G. Bhide, PhD, professor of developmental neuroscience and director of the Center for Brain Repair at FSU, told Medscape Medical News. "They are bad because the next generation is affected. But they're good because as long as the exposure no longer occurs, 2 or 3 generations later, that's gone."

The mice, which lacked taste receptors for aspartame, were the same age and weight in all three groups. Because the only difference was exposure to the artificial sweetener, Bhide says it suggests a causal link.

"Extrapolation of data from well-controlled laboratory experiments in mice to humans is always risky," Bhide said. "The extrapolations give us insights into what could happen rather than what will happen."

Potential Mechanisms

Although scientists can't say for certain how UPFs affect brain health, there are several theories. UPFs may influence an inflammatory immune response, which has been linked to depression and dementia. Consumption of highly processed foods may also disrupt the gut microbiome, Chan said, which, in turn, may increase depression risk.

"This is an important potential mechanism linking ultraprocessed food to depression since there is emerging evidence that microbes in the gut have been linked with mood through their role in metabolizing and producing proteins that have activity in the brain," he said.

In addition, with UPFs that contain aspartame, there could be a more direct link to brain function. In the gastrointestinal track, the sweetener is quickly broken down into methanol, aspartic acid, and phenylalanine. All three enter the bloodstream, cross the blood-brain barrier, and are neuroactive.

"Phenylalanine is a precursor for neurotransmitters in the brain, and aspartic acid activates the glutamate excitatory neurotransmitter receptor," Bhide said. "The effects we've seen could be due to these metabolites that have a direct effect on the brain function."

Time to Act?

Some researchers are building a case for classifying UPFs as addictive substances. Others are calling for additional research on UPF safety that is conducted outside the food industry.

There has also been some discussion of placing warning labels on UPFs. However, there is disagreement about what information should be included and how consumers might interpret it. The question of which food products are UPFs and which are not also isn't settled. The NOVA system may be widely used, but it still has its detractors who believe it misclassifies some healthy foods as ultraprocessed.

Chan and other experts say the research conducted thus far requires additional corroboration to inform appropriate public health interventions. That would likely take the form of a large, randomized trial with one group of participants eating a healthy diet and the other consuming large amounts of UPFs.

"This type of study is extremely challenging given the number of people that would have to be willing to participate and be willing to eat a very specific diet over a long period of time," Chan said. "I am also not sure it would be ethical to assign people to such a diet, given what we already know about the potential health effects of UPFs."

Thiagarajan and others have called on funding agencies to direct more grant monies toward studies of UPFs to better understand their effect on brain health.

"Given the magnitude of the problem and given that there is a fair bit of evidence that points to a potential causal link, then we damn well better put money into this and get to the bottom of it," she said.

Others are looking to the FDA to increase the agency's scrutiny of food additives. While some additives such as artificial sweeteners have a place in diets of people with diabetes or obesity, Bhide suggests it may be wise for healthy individuals to reduce their daily intake of UPFs.

"Our data raise this to a different level because of the transgenerational transmission, which has never been shown before," he said. "We are saying that the FDA should look in preclinical models at germ cells and maybe transgenerational transmission before approving any food additive."

Kelli Whitlock Burton is a reporter for Medscape Medical News covering neurology and psychiatry.

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