Medical Bulletin 20/ March/ 2024

Even small dose of Liquorice can elevate blood pressure, finds study

According to a study conducted by researchers at Linköping University, Sweden, consuming even small quantities of liquorice can lead to an increase in blood pressure. Those who react most strongly also display indications of cardiac strain.

The study was published in The American Journal of Clinical Nutrition.

Liquorice is produced from the root of plants of the Glycyrrhiza species and has long been used as a herbal remedy and flavouring. However, it is known that eating liquorice can also raise blood pressure. This is mainly due to a substance called glycyrrhizic acid that affects the body's fluid balance through effects on an enzyme in the kidney. High blood pressure, in turn, increases the risk of cardiovascular disease.

Both the European Union and the World Health Organization have concluded that 100 mg of glycyrrhizic acid per day may be safe to eat for most individuals.

In the study, 28 participants aged 18-30 were split into two groups. They were instructed to alternate between consuming liquorice and a control product containing salmiak, which gives salty liquorice its flavour. Participants were randomly assigned to eat either liquorice or the control product for two weeks, take a break for two weeks, and then eat the other variety for two weeks. Participants monitored their blood pressure daily, and at the end of each period, researchers evaluated hormone levels, salt balance, and heart workload to compare the effects of both substances.

The study found that liquorice consumption led to an average increase of 3.1 mmHg in participants' blood pressure. Additionally, levels of the hormones, renin and aldosterone, which regulate fluid balance, decreased after consuming liquorice. The most sensitive quarter of participants, identified by the greatest decrease in these hormones, also experienced slight weight gain likely due to increased fluid retention. This group also showed elevated levels of NT-proBNP, indicating heightened fluid volume and heart workload in response to liquorice.

"In the study, we found that a daily intake of liquorice containing 100 mg glycyrrhizic acid raised blood pressure in young healthy people. This hasn't previously been shown for such small amounts of liquorice," said Peder af Geijerstam, doctoral student at the Department of Health, Medicine and Caring Sciences at Linköping University, general practitioner, and lead author of the study.

Reference: Peder af Geijerstam, Annelie Joelsson, Karin Rådholm, Fredrik H Nyström. A low dose of daily licorice intake affects renin, aldosterone, and home blood pressure in a randomized crossover trial. Journal: The American Journal of Clinical Nutrition, 2024; 119 (3): 682 DOI: 10.1016/j.ajcnut.2024.01.011

Metformin use in pregnancy influence offspring brain development: Study

A study published in the Journal Molecular Metabolism revealed that although metformin has positive effects in pregnant mothers, it does not in the offspring as it can cross the placental barrier and may impact the brain development of the child.

With the rise in gestational diabetes and metabolic disorders during pregnancy, metformin is also being prescribed more frequently. It is an oral antidiabetic agent that can cross the placenta and can reach the foetus due to its relatively small molecular size and ability to pass through cell membranes. It may potentially alter neural development or influence mitochondrial function and cellular metabolism, processes that are critical for proper brain development.

For the study, researchers used two mouse models to represent the main causes of gestational diabetes: severe obesity of the mother before pregnancy and excessive weight gain during pregnancy. These metabolic states were achieved by means of different feeding patterns, with the mice receiving either a high-fat or control diet. The antidiabetic treatment of female mice and their offspring took place during the lactation period as this corresponds to the third trimester of a human pregnancy in terms of brain development.

Treatment involved insulin, metformin, or a placebo, whereby the dosage was based on standard human treatments. The research team collected data on the body weight of the mice, analysed various metabolic parameters and hormones, and examined molecular signalling pathways in the hypothalamus.

The results revealed that exposure to anti-diabetic treatment (metformin), in the context of maternal gestational weight gain, resulted in an increased body weight as compared to the control fed or the maternal obese condition. Furthermore, human studies of GDM-affected pregnancies showed that children exposed to metformin in utero are smaller at birth than those whose mothers were treated with insulin. However, metformin-exposed children do become heavier, with higher BMI, in childhood.

“As a result of antidiabetic treatment in the early postnatal period, we were able to identify alterations in the weight gain and hormonal status of the offspring, which were critically dependent on the metabolic state of the mother. Furthermore, sex-specific changes in hypothalamic AMPK signalling in response to metformin exposure were also observed. Together with the metformin-induced shift in the examined hormone levels, the results indicate that the maternal metabolic state must be taken into account before starting the treatment of gestational diabetes.” explained Dr. Rachel Lippert, Junior Research Group Leader.

Reference: Lídia Cantacorps, Jiajie Zhu, Selma Yagoub, Bethany M. Coull, Joanne Falck, Robert A. Chesters, Katrin Ritter, Miguel Serrano-Lope, Katharina Tscherepentschuk, Lea-Sophie Kasch, Maya Paterson, Paula Täger, David Baidoe-Ansah, Shuchita Pandey, Carla Igual-Gil, Annett Braune, Rachel N. Lippert; Developmental metformin exposure does not rescue physiological impairments derived from early exposure to altered maternal metabolic state in offspring mice; Journal: Molecular Metabolism; DOI: 10.1016/j.molmet.2023.101860

Weight loss by diabetes drug linked to "anti-hunger" molecule, finds study

Researchers from Stanford Medicine and Harvard Medical School have discovered an “anti-hunger” molecule that is produced after vigorous exercise is responsible for the moderate weight loss caused by the diabetes medication metformin.

The finding published in the journal Nature Metabolism revealed the critical role the molecule, called lac-phe, plays in metabolism, exercise and appetite which may help to discover a new class of weight loss drugs.

Many people with diabetes who are prescribed metformin lose around 2% to 3% of their body weight within the first year of starting the drug. Although this amount of weight loss is modest when compared with the 15% or more often seen by people taking semaglutide drugs, the discoveries that led to those drugs also grew from observations of relatively minor, but reproducible, weight loss in people taking first-generation versions of the medications.

“Until now, the way metformin, which is prescribed to control blood sugar levels, also brings about weight loss has been unclear,” said Jonathan Long, PhD, an assistant professor of pathology. “Now we know that it is acting through the same pathway as vigorous exercise to reduce hunger. Understanding how these pathways are controlled may lead to viable strategies to lower body mass and improve health in millions of people.”

The researchers observed obese laboratory mice who were given metformin and found increased levels of lac-phe in their blood. They ate less than their peers and lost about 2 grams of body weight during the nine-day experiment.

In the study, Long and colleagues analyzed blood plasma samples from people with Type 2 diabetes before and 12 weeks after starting metformin treatment. They found significant increases in lac-phe levels post-metformin. Additionally, among 79 participants in a multi-ethnic atherosclerosis study taking metformin, those on the drug had higher circulating lac-phe levels compared to non-users.

Moreover, a statistical analysis of individuals in the atherosclerosis study who experienced weight loss over the study and follow-up period revealed a significant connection between metformin usage, lac-phe production, and weight reduction.

“It was nice to confirm our hunch experimentally. The magnitude of effect of metformin on lac-phe production in mice was as great as or greater than what we previously observed with exercise. If you give a mouse metformin at levels comparable to what we prescribe for humans, their lac-phe levels go through the roof and stay high for many hours.” said Long. “These findings suggest there may be a way to optimize oral medications to affect these hunger and energy balance pathways to control body weight, cholesterol and blood pressure. I think what we’re seeing now is just the beginning of new types of weight loss drugs.”

Reference: Journal: Nature Metabolism