Medically Speaking

Fasting, according to a recent study from the Icahn School of Medicine at Mount Sinai, may make it more difficult to fight infections and increase your risk of developing heart disease. The study, which used mouse models, is one of the first to show that skipping meals causes the brain to react in a way that damages immune cells. The findings, which focus on breakfast, were published in the journal Immunity and may help researchers better understand how long-term fasting affects the body.

“There is a growing awareness that fasting is healthy, and there is indeed abundant evidence for the benefits of fasting. Our study provides a word of caution as it suggests that there may also be a cost to fasting that carries a health risk,” said lead author Filip Swirski, PhD, Director of the Cardiovascular Research Institute at Icahn Mount Sinai, adding, “This is a mechanistic study delving into some of the fundamental biology relevant to fasting. The study shows that there is a conversation between the nervous and immune systems.”

Researchers wanted to learn more about how fasting affects the immune system, from a short fast of a few hours to a longer fast of 24 hours. They looked at two groups of mice. The first group ate breakfast immediately after waking up (breakfast is their largest meal of the day), while the second group did not. Blood samples were taken from both groups of mice when they awoke (baseline), four hours later, and eight hours later.

When researchers examined the blood work, they noticed a distinct difference in the fasting group. The researchers noticed a difference in the number of monocytes, which are white blood cells that are produced in the bone marrow and travel throughout the body, where they play a variety of important roles ranging from fighting infections to heart disease to cancer.

All mice had the same number of monocytes at the start. Monocytes in mice from the fasting group, on the other hand, were significantly affected after four hours. Researchers discovered that 90% of these cells vanished from the bloodstream after eight hours, and the number continued to decline. Monocytes in the non-fasting group, on the other hand, were unaffected.

Researchers discovered that in fasting mice, monocytes returned to the bone marrow to hibernate. Concurrently, the bone marrow’s ability to produce new cells decreased. Monocytes in the bone marrow, which have a short lifespan, changed dramatically. They lived longer because they remained in the bone marrow and aged differently than monocytes that remained in the blood.

The researchers fasted the mice for up to 24 hours before reintroducing food. Within a few hours, the cells that had been hiding in the bone marrow were released into the bloodstream. This surge resulted in increased inflammation. Instead of protecting the body from infection, these altered monocytes were more inflammatory, making it less resistant to infection.

This is one of the first studies to establish a link between the brain and these immune cells while fasting. The researchers discovered that specific brain regions controlled the monocyte response during fasting. Fasting causes a stress response in the brain, which is what causes people to feel “hangry” (hungry and angry), and this immediately causes a large-scale migration of these white blood cells from the blood to the bone marrow, and then back to the bloodstream shortly after food is reintroduced.

While there is evidence of the metabolic benefits of fasting, Dr. Swirski emphasises that this new study is a useful advance in the full understanding of the body’s mechanisms.

“The study shows that, on the one hand, fasting reduces the number of circulating monocytes, which one might think is a good thing, as these cells are important components of inflammation. On the other hand, the reintroduction of food creates a surge of monocytes flooding back into the blood, which can be problematic. Fasting, therefore regulates this pool in ways that are not always beneficial to the body’s capacity to respond to a challenge such as an infection,” said Dr. Swirski, adding, “Because these cells are so important to other diseases like heart disease or cancer, understanding how their function is controlled is critical.”

Dementia is a major global public health hazard that currently affects 50 million people and is expected to impact more than 150 million people by 2050. Obesity, as measured by the body mass index, is a persistent global issue (BMI). Obesity in middle age has been linked to an increased risk of dementia in previous studies. However, it is yet uncertain if BMI and dementia risk are linked.

Researchers from Boston University Chobanian & Avedisian School of Medicine and the Chinese Academy of Medical Sciences & Peking Union Medical College have shown that various patterns of BMI changes during a person’s life cycle may be a predictor of dementia risk.

“These findings are important because previous studies that looked at weight trajectories didn’t consider how patterns of weight gain/stability/loss might help signal that dementia is potentially imminent,” explained corresponding author Rhoda Au, PhD, professor of anatomy and neurobiology.

“These findings are important because previous studies that looked at weight trajectories didn’t consider how patterns of weight gain/stability/loss might help signal that dementia is potentially imminent,” explained corresponding author Rhoda Au, PhD, professor of anatomy and neurobiology.

A set of individuals in the Framingham Heart Study were tracked for 39 years and their weight was assessed every 2-4 years. The researchers studied distinct weight trends (stable, growth, loss) between people who became demented and those who did not. They discovered that the general trend of decreased BMI was linked to an increased chance of getting dementia.

Further investigation revealed a subgroup with a trend of first increasing BMI followed by dropping BMI, both happening within midlife, which looked to be key to the declining BMI-dementia connection.
Weight monitoring is generally simple for people, family members, and primary care providers, according to Au.

“If after a steady increase in weight that is common as one gets older, there is an unexpected shift to losing weight post midlife, it might be good to consult with one’s healthcare provider and pinpoint why. There are some potential treatments emerging where early detection might be critical in the effectiveness of any of these treatments as they are approved and become available,” she added.

The researchers hope this study will illustrate that the seeds for dementia risk are being sowed across many years, likely even across the entire lifespan. “Dementia is not necessarily inevitable and monitoring risk indicators such as something as easy to notice as weight patterns, might offer opportunities for early intervention that can change the trajectory of disease onset and progression.”

While increasing physical activity, eating better, and meeting new people are all excellent habits, new CU Boulder study shows that gardening can have a substantial impact. The first-ever, randomised, controlled trial of community gardening, funded by the American Cancer Society, discovered that people who began gardening ate more fibre and got more physical activity—two recognised strategies to lessen the risk of cancer and chronic illnesses. They also saw a considerable reduction in tension and anxiety. The findings were reported in the Lancet Planetary Health journal.

“These findings provide concrete evidence that community gardening could play an important role in preventing cancer, chronic diseases, and mental health disorders,” said senior author Jill Litt, a professor in the Department of Environmental Studies at CU Boulder.

Filling a research need Litt has devoted most of her career looking for low-cost, scalable, and long-term approaches to minimise illness risk, particularly in low-income populations. Gardening seemed like a good place to start. “No matter where you go, people say there’s just something about gardening that makes them feel better,” said Litt, who is also a researcher with the Barcelona Institute for Global Health.

But solid science on its benefits is hard to come by. Without evidence, it’s hard to get support for new programs, she said.
Some modest observational studies have discovered that gardeners consume more fruits and vegetables and maintain a better weight. However, it has been unclear whether healthy people just plant more or whether gardening impacts health.
Only three studies have used the randomised controlled trial, the highest standard of scientific research, to investigate the pastime. None have explicitly examined communal gardening.

Litt recruited 291 non-gardening people from the Denver region, with an average age of 41. More than one-third were Hispanic, and more than half were from low-income families. After the final spring frost, half of the participants were assigned to the communal gardening group, while the other half were assigned to a control group that was instructed to wait one year before beginning gardening.

Through the nonprofit Denver Urban Gardens programme and a research partner, the gardening club got a free community garden plot, seeds and seedlings, and an introductory gardening workshop.
Both groups completed surveys about their food consumption and mental health, had their bodies measured, and wore activity trackers on a regular basis.

An increase in fibre
By the autumn, individuals in the gardening group were consuming 1.4 grammes more fibre per day than the control group, a 7% increase. The authors highlight that fibre has a significant impact on inflammatory and immunological responses, impacting everything from how we metabolise food to the health of our gut flora to our susceptibility to diabetes and certain malignancies.

The average adult consumes less than 16 grammes of fibre per day, despite doctors’ recommendations of 25 to 38 grammes.
“An increase of one gramme of fibre can have huge, good benefits on health,” said co-author James Hebert, director of the cancer prevention and control programme at the University of South Carolina. The gardening group also increased their weekly physical activity by roughly 42 minutes. Public health organisations suggest at least 150 minutes of physical exercise each week, which only one-quarter of the US population meets. Participants satisfied 28% of the criteria by visiting the community garden two to three times each week.

Many DUG participants reside in places where access to inexpensive fresh fruits and vegetables is otherwise severely restricted. Some are low-income immigrants who now live in flats; having a garden plot helps them to cultivate food from their native country and pass on traditional recipes to their family and neighbours.
The social link is also enormous.

“Even if you come to the garden looking to grow your food on your own in a quiet place, you start to look at your neighbour’s plot and share techniques and recipes, and over time relationships bloom,” said Litt, noting that while gardening alone is good for you, gardening in the community may have additional benefits. “It’s not just about the fruits and vegetables. It’s also about being in a natural space outdoors together with others.”

Litt said she hopes the findings will encourage health professionals, policymakers and land planners to look to community gardens, and other spaces that encourage people to come together in nature, as a vital part of the public health system. The evidence is clear, she said.

Researchers from the University of Illinois at Chicago evaluated 80 people with nonalcoholic fatty liver disease and discovered that those who followed an alternate-day fasting diet and exercised were able to improve their health.
The researchers report in Cell Metabolism that over a three-month period, people who exercised and alternated feast and fast days (eating without restriction one day and 500 calories or less the next) had increased insulin sensitivity and decreased liver fat, weight, and ALT, or alanine transaminase enzymes, which are markers for liver disease.

Nonalcoholic fatty liver disease is characterised by the accumulation of fat and inflammation in patients who consume little to no alcohol. The disease affects approximately 65% of obese adults, and it is strongly linked to the development of insulin resistance and Type 2 diabetes. If left untreated, fatty liver disease can progress to more serious complications such as cirrhosis or liver failure, but there are few effective treatment options.

Krista Varady, the study’s author, called the findings “pretty amazing.”

“When we compared the results of our study groups, we saw clearly that the most improved patients were in the group that followed the alternate-day fasting diet and exercised five days a week,” said Varady, professor of nutrition at the College of Applied Health Sciences.

“The people who only dieted or only exercised did not see the same improvements, which reinforces the importance of these two relatively inexpensive lifestyle modifications on overall health and on combating chronic diseases like fatty liver disease.”

Participants in the clinical trial were randomly assigned to one of four groups: alternate-day fasting, aerobic exercise, a combined group, or a control group in which no changes were made to their behaviours. Diet group participants tracked their food intake, while exercise group participants used an elliptical machine in Varady’s lab for one hour five days a week.

Varady said the study did not test whether alternate-day fasting was better or worse than other diets when combined with exercise, but she was surprised by how few people dropped out.

“Alternate-day fasting and exercise interventions can be difficult for people to stick to and in prior studies we have seen significant dropout. It was very interesting to see that in this trial we had very high adherence to the interventions,” said Varady, who thought the study’s implementation at the beginning of the COVID-19 pandemic in 2020 could be a plausible explanation for the variation.

The study authors also noted that there were no serious safety events during the trial — the patients were able to safely maintain the diet and exercise for the three-month study, which Varady believes is an indicator that the intervention may be a good option for people with fatty liver disease who want to improve their health without pharmaceuticals, which can have side effects.

The authors write in their paper, “Effect of alternate day fasting combined with aerobic exercise on non-alcoholic fatty liver disease: A randomized controlled trial,” which is the first to look at the effect of intermittent fasting combined with exercise on non-alcoholic fatty liver disease outcomes: “Our findings also indicate that the combination intervention was effective for reducing body weight, fat mass, waist circumference, ALT, fasting insulin, insulin resistance, and increasing insulin sensitivity, among patients with obesity and NAFLD, versus controls.”

An international team of researchers lead by Lithuanian experts adds to the growing body of data that intracranial pressure is important in normal-tension glaucoma, which accounts for up to 50% of all glaucoma cases. A recent clinical study discovered that low intracranial pressure is linked to impaired patient vision, particularly in the nose zone.

Optic nerve degeneration produces glaucoma, one of the main causes of blindness in persons over the age of 60. In glaucoma patients, increased pressure inside the eye (called intraocular pressure or IOP) is frequently noted. However, not everyone who has ocular hypertension develops glaucoma. Furthermore, glaucoma can develop in the presence of normal IOP.

According to several research, the prevalence of so-called normal tension glaucoma (NTG) among patients in the global population ranges from 30 to 90%.  “Contemporary medicine has methods to treat elevated eye pressure and to slow or even stop the damage to the optic nerve. However, these methods do not work in the case of normal tension glaucoma. There is a growing awareness among the scientific community, that glaucoma is a condition caused by two pressures – inside the eye and the skull,” says professor Arminas Ragauskas from Kaunas University of Technology (KTU), Lithuania.

Ragauskas, the Head of KTU’s Health Telematics Science Institute, invented the non-invasive intracranial pressure measuring method employed in the study.

He goes on to explain that the optic nerve is anatomically connected to the brain and is surrounded by cerebrospinal fluid. Intracranial pressure (ICT), which is pressure within our skull measured in cerebrospinal fluid, and intraocular pressure (IOP) can both impact the optic nerve’s health. Recently, researchers have focused on the balance between the two pressures, known as translaminar pressure differential (TPD), and its relationship to the development of glaucoma.

A new study including 80 patients with early-stage normal tension glaucoma (NTG) was done by researchers from Lithuanian, Israeli, and American universities. Between January and October 2018, 300 NTG patients were sent to the Eye Clinic at the Lithuanian University of Health Sciences.

Several measures were taken throughout the investigation, including intraocular pressure (IOP), intracranial pressure (ICP), and visual field perimetry. TPD = IOP – ICP was used to compute the translaminar pressure differential (TPD). There were five zones in the visual field: nasal, temporal, peripheral, central, and paracentral.

The study found multiple statistically significant associations between intracranial pressure, TPD, and changes in visual field. The greater the TPD, the more substantial the impairment to the patient’s visual field. The nasal zone had the most substantial visual field reductions.

“Visual field loss means only one thing – a person is becoming blind. That’s why it is so important to understand the causes of this condition and to reverse it. We are all aware of the dire outcome,” says Prof Ragauskas.

According to the researchers, greater TPD might be considered a risk factor for the detrimental development of normal tension glaucoma. Because TPD is computed by subtracting ICP from IOP, the lower the intracranial pressure reading, the greater the TPD. Thus, decreased intracranial pressure may be a risk factor in normal-tension glaucoma.

“The idea that brain pressure is related to the visual field is not new. Several years ago, we conducted a series of experiments studying the links between visual field and intracranial pressure, using the non-invasive technology developed here, at KTU. In the conferences that followed, I saw how our new idea was met with excitement by the international community of ophthalmologists,” says Prof Ragauskas.

The link between intracranial pressure and glaucoma opens up new possibilities for medical practitioners to investigate the cause and potential therapy of this condition. In addition, data supporting this concept has come in from research organisations operating all around the world in recent years. Prof Ragauskas claims that his study has contributed to the expanding amount of data on the subject, both directly and indirectly.

The intracranial pressure was measured in the above-mentioned study using a two-depth Transcranial Doppler (Vittamed UAB, Lithuania) created by Prof Ragauskas’ team at the Kaunas University of Technology laboratories. Unlike the traditional method of monitoring intracranial pressure, which entails drilling a tiny hole into the patient’s skull, Prof Ragauskas’ innovation uses ultrasound to measure brain pressure non-invasively through the eye. The invention’s industrial uses were patented in the United States and Europe.

“We are not competing with invasive methods, but heading towards an entirely new direction. At the moment, I see that ophthalmology is the field where our technology is needed most, and we are using it for research purposes. However, we are constantly developing our invention and have recently patented a couple of new applications, which might be used in other contexts where measuring intracranial pressure is crucial. For example, in long-term space missions,” says KTU professor Ragauskas.

A new study shows how cannabidiol (CBD), a molecule found in cannabis, reduces seizures in numerous types of treatment-resistant paediatric epilepsy. The present study, led by experts from NYU Grossman School of Medicine, showed that CBD blocked signals transmitted by lysophosphatidylinositol, a molecule (LPI). LPI is present in neurons, which are brain cells, and is assumed to boost nerve transmissions as part of regular operation.

However, sickness can cause LPI to be hijacked and cause seizures. The study, which was published online on February 13 in Neuron, validated a prior result that CBD inhibits LPI’s capacity to enhance nerve impulses in a brain area known as the hippocampus. The recent findings imply, for the first time, that LPI decreases anti-seizure signals, further explaining the benefit of CBD therapy.

“Our results deepen the field’s understanding of a central seizure-inducing mechanism, with many implications for the pursuit of new treatment approaches,” said corresponding author Richard W. Tsien, chair of the Department of Physiology and Neuroscience at NYU Langone Health.

“The study also clarified how CBD counters seizures, but more broadly how circuits are balanced in the brain,” added Tsien. “Related imbalances are present in autism and schizophrenia so that the paper may have a broader impact.”

The findings focus on how each neuron “fires” to send an electrical pulse along an extension of itself until it reaches a synapse, which is the gap that joins it to the next cell in a neural pathway. When the pulse reaches the cell’s end before the synapse, it causes the release of neurotransmitters, which float over the gap and effect the next cell in line. When such signals overlap, the cell is either encouraged to fire (excited) or inhibited from firing (inhibition). The right balance of the two is critical for brain function; too much excitement induces seizures.

The new study examined multiple rat models to investigate seizure processes, generally by monitoring information-carrying electrical current flows with fine-tipped electrodes. Other studies investigated the effect of LPI by genetically eliminating its major signalling partner or by detecting LPI release after seizures.

The researchers discovered that either genetically modifying mice to lack GPR55 or pre-treatment with plant-derived CBD prior to seizure-inducing stimuli inhibited LPI-mediated effects on both excitatory and inhibitory synaptic transmission. While previous research has indicated GPR55 as a CBD seizure-reduction target, the new study revealed a more comprehensive, hypothesised mechanism of action.

The authors believe that CBD inhibits a “positive feedback loop” in which seizures boost LPI-GPR55 signalling, which presumably stimulates more seizures, which raises LPI and GPR55 levels. The postulated vicious loop is one method that might explain recurring epileptic seizures, however further research is required to prove this.

Furthermore, while the present study focused on the plant-based cannabinoid CBD, the authors point out that LPI is part of a signalling network that includes “endocannabinoids” such as 2-Arachidonoylglycerol (2-AG), which occur naturally in human tissues. CBD also regulates LPI and 2-AG target receptors, although their activities at the synapse vary. While LPI amplifies incoming electrical impulses, endocannabinoids such as 2-AG respond to increased brain activity by decreasing neurotransmitter release from nerve cells. Surprisingly, LPI and 2-AG can be transformed into one other by enzyme activity.

“Theoretically, the brain could control activity by toggling between pro-excitatory LPI and the restorative actions of 2-AG,” said first study author Evan Rosenberg, PhD, a post-doctoral scholar in the Tsein’s lab. “Drug designers could inhibit the enzymes that underpin LPI production or promote its conversion to 2-AG, as an additional approach to control seizures. LPI could also serve as a biomarker of seizures or predictor of clinical responsiveness to CBD, providing an area of future research.”