Medical Bulletin 31/ July/ 2024

Researchers at UC San Francisco have discovered a connection between a diet rich in vitamins and minerals, particularly one low in added sugar, and a younger biological age at the cellular level.

The study, published in journal JAMA Network Open, examined the impact of three different healthy eating measures on an "epigenetic clock" – a biochemical test that estimates health and lifespan. Results showed that the healthier the participants' diets, the younger their cells appeared. However, even among those with healthy eating habits, each gram of added sugar consumed was linked to an increase in their epigenetic age.

This study is among the first to demonstrate a link between added sugar and epigenetic aging, and the first to investigate this connection in midlife women.

The women in the study reported an average daily consumption of 61.5 grams of added sugar, with individual intakes ranging from 2.7 to 316 grams per day. For context, a bar of milk chocolate contains about 25 grams of added sugar, while a 12-ounce can of cola has approximately 39 grams. The U.S. Food and Drug Administration recommends that adults limit their added sugar intake to no more than 50 grams per day.

In the cross-sectional study, researchers analysed food records. They compared the women's diets, scored for adherence to a Mediterranean-style diet and a diet linked to lower chronic disease risk, with epigenetic clock measures derived from saliva samples. Additionally, they created an "Epigenetic Nutrient Index (ENI)" based on nutrients linked to anti-oxidative, anti-inflammatory processes, and DNA maintenance, including vitamins A, C, B12, E, folate, selenium, magnesium, dietary fiber, and isoflavones.

Adherence to any healthy diet was significantly associated with lower epigenetic age, with the Mediterranean diet showing the strongest link. However, separate analysis revealed that added sugar consumption was linked to accelerated biological aging, even within healthy diets.

Reference: Chiu, D. T., et al. (2024). Essential Nutrients, Added Sugar Intake, and Epigenetic Age in Midlife Black and White Women: NIMHD Social Epigenomics Program. JAMA Network Open. doi.org/10.1001/jamanetworkopen.2024.22749.

Scientists at the University of Florida, USA, have conducted a randomized crossover trial to examine the cardiometabolic effects of extra virgin olive oil as part of a whole-food, plant-based vegan diet.

The trial's findings were published in the Journal of the American Heart Association.

Low-fat, whole-food, plant-based diets emphasize unrefined foods and limit processed products, refined grains, added sugars, and oils, including restricting vegetable oil fat intake to less than 10%-15% of energy intake. The Mediterranean diet, while also plant-based, includes extra virgin olive oil (EVOO) as the main fat source, with moderate seafood, poultry, and dairy consumption, and up to 35%-40% of energy intake from vegetable oils.

To compare the cardiometabolic effects of EVOO within a low-fat, whole-food, plant-based diet, scientists at the University of Florida have conducted a randomized crossover trial called "The Recipe for Heart Health trial."

The study involved 40 adults aged 18 to 79 with a cardiovascular disease risk of 5% or higher. They were randomly assigned to follow one of two whole-food, plant-based diets for four weeks each. One diet included four tablespoons of extra virgin olive oil daily, while the other included less than one teaspoon daily. Participants switched diets after a one-week break.

To help them stick to the diets, participants attended weekly online cooking classes led by a dietitian/chef. The researchers considered age, sex, and weight changes when analysing the effects of the two diets on LDL cholesterol and other heart health markers like blood lipids, blood sugar levels, and inflammation.

The study measured blood metabolite levels after each 4-week diet period and found that both diets significantly reduced LDL cholesterol, with no major differences between the high- extra virgin olive oil and low- extra virgin olive oil diets. Both diets also similarly lowered total cholesterol, apolipoprotein B, HDL cholesterol, glucose, and high-sensitivity C-reactive protein (CRP) levels compared to the start. However, during the first 4-week period, the low- extra virgin olive oil diet reduced LDL cholesterol, total cholesterol, HDL cholesterol, apolipoprotein B, and glucose levels more than the high- extra virgin olive oil diet. These differences evened out in the second 4-week period.

When looking at the order in which the diets were followed, LDL cholesterol dropped significantly in those who went from high to low extra virgin olive oil, but increased in those who went from low to high extra virgin olive oil. The low to high extra virgin olive oil sequence also raised total cholesterol, HDL cholesterol, and glucose levels. Both diets led to weight loss, but the low- extra virgin olive oil diet resulted in more significant weight reduction.

The findings revealed that both high and low extra virgin olive oil intake reduced blood LDL-C levels, even though total fat made up 48% of total energy during the high-EVOO period and 32% during the low- extra virgin olive oil period.

Reference: Krenek AM. 2024. Recipe for Heart Health: A Randomized Crossover Trial on Cardiometabolic Effects of Extra Virgin Olive Oil Within a Whole‐Food Plant‐Based Vegan Diet. Journal of the American Heart Association. https://www.ahajournals.org/doi/10.1161/JAHA.124.035034

Primary liver cancer is the sixth most common cancer worldwide and the third leading cause of cancer deaths. Major risk factors for liver cancer include chronic infections with hepatitis B or C viruses, exposure to aflatoxins, heavy alcohol use, tobacco use, and metabolic disorders like non- alcoholic fatty liver disease, obesity, and type 2 diabetes.

Since liver cancer often has a poor prognosis, finding ways to prevent it, including using certain medications, is very important for public health. Recently, there has been a lot of research into how medications like aspirin, metformin, and statins might help reduce the risk of liver cancer.

Cholesterol absorption inhibitors, bile acid sequestrants, fibrates, niacin, and omega-3 fatty acids are types of non-statin medications used to manage cholesterol and lipid levels. Each type works differently to help lower cholesterol.

Researchers from the National Cancer Institute studied these five types of non-statin cholesterol-lowering drugs to see if they were linked to liver cancer risk.

Previous research has suggested that statin cholesterol-lowering drugs may reduce the risk of liver cancer. A new study, however, investigated non-statin cholesterol-lowering medications and found that one type was associated with a reduced risk of liver cancer. The findings have been published in CANCER, a peer-reviewed journal of the American Cancer Society, by Wiley Online.

In the study, researchers used data from the Clinical Practice Research Datalink (CPRD) and analysed 3,719 liver cancer cases, comparing them with 14,876 people without cancer and matching them also based on type 2 diabetes and chronic liver disease.

The study found that using cholesterol absorption inhibitors was linked to a 31% lower risk of liver cancer overall. This was also true for people with diabetes and liver disease. Statins were associated with a 35% lower risk of liver cancer.

However, no connection was found between liver cancer risk and the use of fibrates, omega-3 fatty acids, or niacin. While bile acid sequestrants were linked to a higher risk of liver cancer in the overall analysis, the results were inconsistent when considering diabetes and liver disease, indicating the need for further research.

Reference: Shahriar A. Zamani PhD, Barry I. Graubard PhD, Marianne Hyer MS, Emily Carver BS, Jessica L. Petrick PhD, MPH, Katherine A. McGlynn PhD, MPH; Use of cholesterol-lowering medications in relation to risk of primary liver cancer in the Clinical Practice Research Datalink; CANCER; https://doi.org/10.1002/cncr.35436

Autism spectrum disorder (ASD) is a condition that affects how people learn and interact socially. While awareness of ASD has grown, many aspects of the disorder are still not fully understood.

The exact causes of ASD are not known, but neuroinflammation is believed to play a major role. Research in mice suggested that polyunsaturated fatty acids (PUFAs) and their byproducts during pregnancy might influence the development of ASD. These PUFAs are controlled by the cytochrome P450 (CYP) system and can affect fetal development, leading to symptoms similar to ASD. However, it is not yet clear if these findings apply to humans, and more research is needed.

To learn more, a research team from the University of Fukui looked at the levels of CYP-PUFA in umbilical cord blood samples from newborns. The study, published in Psychiatry and Clinical Neurosciences, aimed to uncover more about the possible causes of autism spectrum disorder (ASD).

The researchers hypothesised that changes in certain fatty acids during pregnancy, like lower levels of EpFA, higher levels of diols, and more enzymes that process EpFA, might affect autism symptoms and daily functioning in children.

To test this idea, they looked at the levels of these fatty acids in umbilical cord blood from 200 babies. They collected the blood right after birth and then assessed the children’s autism symptoms and daily skills when they turned six years old, using information from their mothers.

After analysing the data, the researchers found that a specific compound in the cord blood, called 11,12-dihydroxyeicosatrienoic acids (diHETrE), might be strongly linked to the severity of autism. This compound is a type of fatty acid made from arachidonic acid.

The researchers discovered that higher levels of a molecule called 11,12-diHETrE were linked to problems with social interactions in children, while lower levels of another molecule, 8,9-diHETrE, were associated with repetitive and restrictive behaviors. This link was more pronounced in girls than in boys.

The findings could be important for understanding, diagnosing, and even preventing autism spectrum disorder (ASD). Measuring these molecules in umbilical cord blood at birth might help predict whether a child is likely to develop ASD.

Reference: Takaharu Hirai, Naoko Umeda, Taeko Harada, Akemi Okumura, Chikako Nakayasu, Takayo Ohto‐Nakanishi, Kenji J. Tsuchiya, Tomoko Nishimura, Hideo Matsuzaki. Arachidonic acid‐derived dihydroxy fatty acids in neonatal cord blood relate symptoms of autism spectrum disorders and social adaptive functioning: Hamamatsu Birth Cohort for Mothers and Children (HBC Study). Psychiatry and Clinical Neurosciences, 2024; DOI: 10.1111/pcn.13710