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Change in diet may reduce risk of lethal prostate cancer

By Chukwuma Muanya
07 December 2021   |   4:04 am
A study has shown that there may be an association between diet, the gut microbiome, and lethal prostate cancer.

•Regularly consuming fish could protect against vascular brain disease
A study has shown that there may be an association between diet, the gut microbiome, and lethal prostate cancer.

The study, from the Cleveland Clinic, appears in Cancer Epidemiology, Biomarkers & Prevention.

Researchers used data from the PLCO cancer screening trial, a randomized control trial of 148,000 people. It involved screening 76,685 men aged between 55 and 74 for prostate cancer and then monitoring them for up to 13 years.

Researchers analyzed baseline levels of certain dietary nutrients and metabolites from nearly 700 men. Of these, 173 later died of prostate cancer. The median time between baseline sampling and death for those who developed lethal prostate cancer was 11.69 years.

“Men with higher levels of certain diet-related molecules are more likely to develop aggressive prostate cancer,” said Dr. Nima Sharifi, Director, Genitourinary Malignancies Research Centre, Kendrick Family Endowed Chair for Prostate Cancer Research, Cleveland Clinic, lead researcher on the study

The researchers matched those who died for age, race, time of blood sample, and enrolment date with controls in a ratio of 1:3. Of the 519 men in the control sample, 83.6 per cent remained healthy, and 16.4 per cent had a subsequent non-lethal prostate cancer diagnosis during the study period.

On enrolling in the PLCO cancer screening trial, all participants gave blood samples. Researchers analyzed the blood serum for several different metabolites, some of which are formed by gut bacteria from food intake. They compared results from men who later died of prostate cancer with controls.

Increased risk
The researchers found associations between more aggressive prostate cancer and three metabolites – phenylacetylglutamine, choline, and betaine.

Phenylacetylglutamine is produced when gut bacteria break down phenylalanine, an essential amino acid. Choline and betaine are in some foods, as well as being formed by gut bacteria.

Phenylalanine is in high protein foods, such as dairy, meat, poultry, soy, fish, beans, nuts, and diet sodas sweetened with aspartame. It is an essential part of many proteins and enzymes in the body and, when converted to tyrosine, is used to make the neurotransmitter dopamine.

Choline is found mainly in animal products, such as meat, fish, eggs, and dairy, although pulses, nuts, and seeds are sources for vegans. Foods high in betaine include shellfish, wheat, spinach, and beets.

The researchers found that men with elevated phenylacetylglutamine in their blood serum at the start of the study were 2.5 times more likely to die of prostate cancer than those with the lowest levels. Men with increased choline or betaine had almost twice the risk of lethal prostate cancer as controls.

Sharifi commented: “[Our findings] suggest that food intake has a complex interaction with gut bacteria to affect lethal prostate cancer risk.”

Some gut bacteria convert choline and betaine into trimethylamine and trimethylamine N-oxide (TMAO), which a previous study found might also increase the risk of cardiovascular and neurological disorders. This is the first study to show an association between precursors of TMAO and cancer.

“Betaine and choline are being converted into more toxic chemicals in some. This does not mean they are bad for everyone. It’s the diet-microbe interaction that leads to the cancer,” said Prof. Tim Spector, Professor of Genetic Epidemiology, King’s College, London, and Zoe Study Lead.

Studies have shown that reducing meat intake has associations with lower mortality from cardiovascular disease and cancers. This study would appear to reinforce that message for prostate cancer.

Sharifi said: “Generally, the metabolites associated with lethal prostate cancer are found to be enriched in meat and other animal products.”

However, Spector cautioned: “These metabolites are ubiquitous. It’s difficult to cut them out.”

The authors stress that although this study shows an association between the three metabolites and lethal prostate cancer, it cannot demonstrate a causal link. Sharifi and his team are undertaking further studies to determine “how metabolism in humans interacts with prostate cancer.”

Spector believes that the study: “Adds to the story building on how diet affects cancer mediated by the gut microbiome. We are reversing decades of doctors saying it doesn’t really matter what you eat.”

Meanwhile, health experts associate fish consumption with a lower risk of cerebrovascular disease and the accompanying decline in cognitive function.

A recent cross-sectional study found a link between higher fish intake and lower levels of markers for vascular brain damage in healthy older adults, especially those aged 65–74 years.

The study appeared in the journal Neurology.

The effect of consuming fish two–three times per week on cerebrovascular disease-associated brain markers was similar in magnitude to the effect of high blood pressure, which was associated with increased vascular brain damage.

Cerebrovascular disease, or vascular brain disease, refers to multiple conditions that affect the blood vessels and blood circulation in the brain, such as stroke and vascular malformation.

In addition to causing physical disability, cerebrovascular diseases can result in the development and progression of cognitive impairment and dementia.

Moreover, health experts also associate subclinical cerebrovascular damage — that is, brain abnormalities observed in the early stages of the cerebrovascular disease before its symptoms become evident — with an increased risk of dementia.

Healthy lifestyle modifications, including making dietary changes, increasing physical activity levels, and quitting smoking, can reduce the risk of cerebrovascular disease.

For instance, there is a relation between higher intake of fish and a lower risk of stroke. Fish are an excellent source of omega-3 polyunsaturated fatty acids, which may mediate these benefits on cerebrovascular health.

However, the evidence that fish consumption reduces vascular brain damage before the onset of the cerebrovascular disease is mixed.

A recent cross-sectional study investigated the link between fish consumption and vascular brain damage in healthy older adults before cerebrovascular disease onset.

The study reports an association between eating fish two or more times per week and lower levels of brain abnormalities related to vascular brain damage, especially in individuals under the age of 75 years.

The study’s senior author, Dr. Cecilia Samieri, a senior researcher at the University of Bordeaux in France, explains: “Our results are exciting because they show something as simple as eating two or more servings of fish each week is associated with fewer brain lesions and other markers of vascular brain damage, long before obvious signs of dementia appear. However, eating that much fish did not have a protective effect in people 75 years of age and older.”

The present study analysed data collected between March 1999 and March 2001 as part of the Three-City Study, which aims to understand the relationship between vascular diseases and dementia in people aged 65 years and older.

The analysis involved 1,623 people with an average age of 72.3 years and residing in Dijon, France. Individuals were excluded from the study if they had a dementia diagnosis, a history of stroke, or hospitalization for cardiovascular diseases.

The researchers evaluated the extent of subclinical cerebrovascular damage using brain Magnetic Resonance Imaging (MRI) scans.

They analysed the MRI scans for the presence of three markers associated with subclinical cerebrovascular damage: white matter abnormalities, infarcts and enlargement of perivascular spaces.

White matter consists of nerve fibers, or axons, that relay messages between brain regions. Cerebrovascular disease can result in nerve fiber degeneration and cause damage to the myelin sheath that surrounds the nerve fibers. This leads to white matter abnormalities.

Infarcts are regions of dead tissue resulting from inadequate blood supply. This is often due to a blood clot in a blood vessel.

Perivascular spaces are fluid-filled spaces surrounding blood vessels. When enlarged, they are associated with cerebral small vessel disease.

Each of these markers predicts the extent of cognitive decline related to cerebrovascular disease. However, previous studies have shown that a single measure obtained by combining multiple cerebrovascular disease markers can be a better predictor of cognitive decline than any single marker.

Scientists refer to a combined measure of multiple cerebrovascular disease markers as the global cerebrovascular disease burden.

At inclusion, the researchers assessed the participants’ weekly intake of various food items, including meat, fish, fruits and vegetables, legumes, and cereals, with the help of a brief questionnaire.

They assessed the relation between the global cerebrovascular disease burden and the frequency of fish intake. They noted a link between a higher frequency of fish intake and lower cerebrovascular disease marker levels.

The participants consuming fish two or more times per week had lower combined levels of cerebrovascular disease markers than those who consumed fish less frequently.

Moreover, the strength of the association between lower cerebrovascular disease marker levels and frequency of fish intake was influenced by age. This association was strongest in younger participants aged 65–69 years, but it was not statistically significant in individuals aged over 75 years.

The researchers observed similar results after adjusting for multiple variables, such as age, sex, physical activity levels, education levels, brain volume, and the intake of food items.

Health experts associate high blood pressure with an increased risk of cerebrovascular disease. The authors of the current study observed a similar association between cerebrovascular disease marker levels and high blood pressure, regardless of age of the participants.

To further contextualize the results, the researchers compared the impact of high blood pressure on cerebrovascular disease markers with the frequency of fish intake.

In the participants aged 65–69 years, consuming fish twice per week had a similar effect on cerebrovascular disease marker levels as high blood pressure, but in the opposite direction.

Moreover, the magnitude of the effect of consuming fish four or more times per week on levels of vascular brain damage markers was twice that of high blood pressure.