Dietary curcumin may boost brain DHA: Study

UCLA, March 5, 2021

Increased intake of curcumin could boost levels of docosahexaenoic acid (DHA) in the brain by enhancing its conversion from other omega-3 precursors in the liver, say researchers.

The data, published in Biochimica et Biophysica Acta (BBA), explored the possibility that dietary intake of curcumin increases the production of DHA by influencing precursors such ALA and DPA after previous research showed that curcumin prevents reduced DHA content in the brain following brain trauma and that curcumin plus DHA had additive beneficial effects on plasticity, behaviour and brain DHA content.

“The combined supplementation with curcumin plus DHA reduced the brain content of the DHA precursor n-3 DPA, raising the question as to whether curcumin stimulates the synthesis of DHA,” noted the research team, led by senior author Dr Fernando Gomez-Pinilla from the University of California at Los Angeles.

Using a combination of in vitro cell culture tests and animal modelling, the team found that dietary curcumin has the potential to enhance the production of DHA from its precursor, alpha-linolenic acid (ALA).

“We report novel data showing that curcumin elevates DHA synthesis from omega-3 precursors in liver cells, and that in combination with dietary ALA, curcumin increases DHA content in vivo in both the liver and the brain,” said Gomez-Pinilla and colleagues.  “Enzymes involved in the synthesis of DHA, FADS2 and elongase 2, were concurrently elevated, suggesting that curcumin may increase DHA content, in part, by increasing the pool of enzymes available to facilitate the conversion from either ALA or DPA,” they added.

In addition to identifying the mechanism by which dietary curcumin could increase brain levels of DHA, the US-based research team also report data that suggests dietary intake of curcumin and ALA could reduce anxiety-like behaviours.

Using rat models, the team found that supplementation with curcumin and ALA reduced anxiety-like behaviours.

“Feeding animals a combination of curcumin and ALA elevated DHA content in both the liver and the brain,” said the team. “Furthermore, elevations in brain DHA were closely associated with the reduced anxiety-like behaviour tested by EPM.”

The team also suggested that since the liver is the primary site for most of the DHA synthesis in the body; this raises the question as to whether some of the health effects of curcumin can be attributed to the synthesis of DHA.

“For example, deficient liver biosynthesis of DHA was linked to cognitive impairment in Alzheimer’s patients who showed reduced expression of enzymes involved in DHA synthesis,” noted the team. “These data strongly suggest that curcumin increases the hepatic synthesis of DHA from its precursors.”

Such findings have important implications for human health and the prevention of cognitive disease, suggested the team, adding that the findings may be particularly vital for people eating a plant-based diet or who do not consume fish, a primary source of DHA.

“Taken together, these data suggest that curcumin enhances DHA synthesis, resulting in elevated brain DHA content,” the authors concluded

Can zinc levels predict COVID-19 severity?

Hospital del Mar Research Institute & Pompeu Fabra University, March 11, 2021 

• A recent study examined the links between zinc levels in people hospitalized with COVID-19 and both disease progression and outcome.
• The study found that participants with low zinc levels had a 21% mortality rate compared with 5% in those with healthy zinc levels.
• The time to clinical recovery was approximately three times less in those with healthy serum zinc levels.
• The authors conclude that serum zinc levels could help predict the outcome of individuals with COVID-19.

Zinc is a trace element that is naturally present in certain foods and also available in dietary supplements. The human body requires zinc to maintain a range of biological functions.

For instance, hundreds of enzymes require zinc to function properly. It also plays a role in protein synthesis, DNA synthesis and cell division, wound healing, and immune function.

Zinc possesses an anti-inflammatory effect and has direct antiviral activity. As a result, zinc deficiency may reduce both innate and adaptive immune responses.

In people with a viral infection, such as SARS-CoV-2, the innate immune system is the body’s first-line response to prevent the virus from penetrating and replicating before the adaptive immune system develops targeted protection.

Are zinc levels a risk factor?

People with a SARS-CoV-2 infection have a broad spectrum of possible clinical outcomes ranging from asymptomatic to severe disease. Understanding the risk factors that determine COVID-19 severity is crucial in developing effective early stage treatments.

This need prompted doctors and researchers at Hospital del Mar, Hospital del Mar Medical Research Institute, and the Pompeu Fabra University, all in Spain, to investigate the effect of zinc levels in people with severe COVID-19 on disease progression and clinical outcomes.

The scientists also examined the effect of zinc supplementation to block SARS-CoV-2 replication in the laboratory.

Dr. Robert Güerri-Fernández, a doctor at the Infectious Diseases Service of Hospital del Mar and one of the authors of the study, explains the rationale for the study:

“Zinc is an essential element for maintaining a variety of biological processes, and altering its levels causes increased susceptibility to infections and increased inflammatory response. […] zinc levels and zinc supplementation may prove useful tools to tackle the COVID-19 crisis.”

In the study, which appears in the journal Nutrients, the researchers analyzed data from 249 adults admitted to the hospital’s COVID-19 unit between March 9, 2020, and April 1, 2020. The median age of the participants was 65 years, and 51% were male.

In all, 28% of the participants required intensive care unit admission, and 9% died while in the hospital.

Improved outcomes

Approximately 23% of the participants had low serum zinc levels at admission. Participants with low zinc levels were more likely to experience severe COVID-19 and increased levels of inflammatory markers (interleukin-6 and C-reactive protein).

For the participants with healthy zinc levels, the time to recovery was approximately three times less than for those with a low serum level: 8 days versus 25 days, respectively.

Individuals with low zinc levels had a significantly greater mortality rate (21%) than those in the healthy zinc group (5%).

After adjusting for differences in the participants’ age, sex, comorbidities, and disease severity, the study revealed a significant 6% decrease in mortality with every unit increase of serum zinc at admission.

Laboratory study

In a parallel laboratory experiment, the researchers demonstrated that increased zinc concentrations decreased the replication of SARS-CoV-2 in cell cultures.

Dr. Güerri-Fernández elaborates on the important implication of study results, “We have shown the importance of zinc levels in patients’ blood as an additional predictor of outcome in COVID-19, as well as its potential as a therapeutic tool for treatment.”

The study does have some limitations. For instance, it is observational, so it is not possible to demonstrate causality. In other words, the researchers cannot determine from the findings whether low levels of zinc increase the risk of severe COVID-19 or severe COVID-19 causes zinc to become depleted.

Also, the study is relatively small, and all of the participants came from a single center, which could limit the study’s generalizability.

Dr. Güerri-Fernández highlights the study’s importance and the need for more work:

“We, therefore, propose this variable as a new parameter to predict the evolution of patients, and we propose initiating clinical trials concerning zinc supplementation in patients with low levels admitted for COVID-19 and implementing programs to administer supplements to groups at risk of having low zinc levels to reduce the effects of the pandemic.

The gut mycobiome influences the metabolism of processed foods

New research points to a significant role for fungi to shape metabolism, including fat deposition, and metabolic hormones.

University of Alabama, March 8, 2021

Studies of the microbiome in the human gut focus mainly on bacteria. Other microbes that are also present in the gut — viruses, protists, archaea and fungi — have been largely overlooked.

New research in mice now points to a significant role for fungi in the intestine — the communities of molds and yeasts known as the mycobiome — that are the active interface between the host and their diet.

“We showed that the gut mycobiome of healthy mice was shaped by the environment, including diet, and that it significantly correlated with metabolic outcomes,” said Kent Willis, M.D., an assistant professor at the University of Alabama at Birmingham and co-corresponding author of the study, published in the journal Communications Biology. “Our results support a role for the gut mycobiome in host metabolic adaptation, and these results have important implications regarding the design of microbiome studies and the reproducibility of experimental studies of host metabolism.”

Willis and colleagues looked at fungi in the jejunum of the mouse small intestine, site of the most diverse fungal population in the mouse gut. They found that exposure to a processed diet, which is representative of a typical Western diet rich in purified carbohydrates, led to persistent differences in fungal communities that significantly associated with differential deposition of body mass in male mice, as compared to mice fed a standardized diet.

The researchers found that fat deposition in the liver, transcriptional adaptation of metabolically active tissues and serum metabolic biomarker levels were all linked with alterations in fungal community diversity and composition. Variations of fungi from two genera — Thermomyces and Saccharomyces — were the most strongly associated with metabolic disturbance and weight gain.

The study had an ingenious starting point. The researchers obtained genetically identical mice from four different research animal vendors. It is known that gut bacterial communities vary markedly by vendor. Similarly, the researchers found dramatically different variability by vendor for the jejunum mycobiomes, as measured by sequencing internal transcribed spacer rRNA. At baseline, mice from one of the vendors had five unique fungal genera, and mice from the other three vendors had three, two and one unique genera, respectively.

They also looked at interkingdom community composition — meaning bacteria as well as fungi — and found large baseline bacterial community differences. From this initial fungal and bacterial diversity, they then measured the effects of time and differences in diet — standardized chow versus the highly processed diet — on fungal and bacterial community composition.

The researchers also addressed a fundamental question: Are the fungal organisms detected by next-generation sequencing coming from the diet, or are they true commensal organisms that colonize and replicate in the gut? They compared sequencing of the food pellets, which contained some fungi, and the contents of the mouse jejunum to show the jejunum fungi were true commensal colonizers.

Thus, this study, led by Willis — and co-corresponding author Joseph Pierre, Ph.D., and co-first authors Tahliyah S. Mims and Qusai Al Abdallah, Ph.D., from the University of Tennessee Health Science Center, Memphis, Tennessee — showed that variations in the relative abundance and composition of the gut mycobiome correlate with key features of host metabolism. This lays a foundation towards understanding the complex interkingdom interactions between bacteria and fungi and how they both collectively shape, and potentially contribute to, host homeostasis.

“Our results highlight the potential importance of the gut mycobiome in health, and they have implications for human and experimental metabolic studies,” Pierre said. “The implication for human microbiome studies, which often examine only bacteria and sample only fecal communities, is that the mycobiome may have unappreciated effects on microbiome-associated outcomes.”

The research was mostly done at the University of Tennessee Health Science Center, where Willis was an assistant professor before joining the Division of Neonatology in the UAB Department of Pediatrics last summer.

The translational research in the Willis Lung Lab at UAB seeks to understand how such commensal fungi influence newborn physiology and disease, principally via exploring the gut-lung axis in bronchopulmonary dysplasia, a lung disease of premature newborns. The study in Communications Biology using adult animals, Willis says, helped develop models for on-going research in newborn animals.

Convincing evidence that type 2 diabetes is associated with increased risk of Parkinson’s

Queen Mary University (UK), March 8, 2021

Research from Queen Mary University of London has concluded that there is convincing evidence that type 2 diabetes is associated with an increased risk of Parkinson’s disease. The same study found that there was also evidence that type 2 diabetes may contribute to faster disease progression in patients who already have Parkinson’s.

Treating people with drugs already available for type 2 diabetes may reduce the risk and slow the progression of Parkinson’s. Screening for and early treatment of type 2 diabetes in patients with Parkinson’s may be advisable.

Previous systematic reviews and meta-analyses have produced conflicting results around the link between diabetes and the risk of Parkinson’s disease. This new study, published in the Movement Disorders Journal, used meta-analysis of observational data and meta-analysis of genetic data to evaluate the effect of type 2 diabetes on risk and progression of Parkinson’s disease.

Corresponding author Dr Alastair Noyce from Queen Mary University of London said: “This research brings together the results from many other studies to provide convincing evidence that type 2 diabetes likely affects not only Parkinson’s risk, but also Parkinson’s progression. There are many treatment strategies for type 2 diabetes, including prevention strategies, which may be re-purposed for the treatment of Parkinson’s.”

 

Umbrella review concludes protective effect for omega 3 against cardiovascular death

Yonsei University College of Medicine (South Korea), March 8 2021. 

A review of meta-analyses of clinical trials and cohort studies published in the February 2021 issue of the European Review for Medical and Pharmacological Sciences added more evidence to a protective effect for omega 3 fatty acid supplementation against death from cardiovascular causes.

1. Choi of Yonsei University College of Medicine Korea and colleagues selected 29 articles for their review, among which 31 meta-analyses of randomized clinical trials and four meta-analyses of observational cohort studies were identified as statistically significant. The studies’ cardiovascular outcomes included cardiovascular, cardiac, and coronary events; cardiovascular, cardiac, and coronary deaths; arrhythmiaor sudden death; myocardial infarction; stroke or transient ischemic attack; postoperative atrial fibrillation; recurrent atrial fibrillation; and a composite outcome of total mortality from major cardiovascular causes.

A significantly lower risk of experiencing the composite outcome of total mortality from major cardiovascular causes was found among subjects who received omega 3 fatty acid supplements in comparison with those who did not receive the supplements. The protective association was still significant after restricting the analysis to large trials that included over 1,000 participants.

“To the best of our knowledge, an umbrella review focusing only omega 3 effects on cardiovascular outcomes has not been conducted,” Dr Choi and colleagues wrote. “In particular, in this current review study, we aimed to identify true associations between omega 3 fatty acids and cardiovascular outcome more strictly by excluding biases and performing subgroup analyses.”

“Our umbrella review indicates that omega 3 fatty acids supplementation reduces overall mortality from cardiovascular causes,” they concluded. “Even though a few large randomized clinical trials showed no evidence of clinical effect of omega 3 on cardiovascular outcomes, our comprehensive review study still provides a clue of clinical utility of omega 3 fatty acids supplementation.”

Study finds increased risk of death among breast cancer patients who drink sugar-sweetened soda

University of Buffalo, March 10, 2021

New research from the University at Buffalo suggests that breast cancer patients who drink sugar-sweetened beverages regularly are at increased risk for death from any cause and breast cancer in particular.

Compared to women who never or rarely drank non-diet soda, those who reported drinking non-diet soda five times or more per week had a 62% higher likelihood of dying from any causes, and were 85% more likely to die from breast cancer specifically. The findings were published online ahead of print March 2 in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.

Research on soda and breast cancer is fairly new, says study first author Nadia Koyratty, a Ph.D. candidate in the Department of Epidemiology and Environmental Health in UB’s School of Public Health and Health Professions. Because breast cancer is so common, recommendations regarding lifestyle choices to breast cancer survivors are of considerable importance. And, despite the negative health outcomes associated with drinking soda, such as weight gain, Type 2 diabetes and cardiovascular disease, many people continue to drink sugar-sweetened sodas.

There have been only a few observational studies examining the association between sugar-sweetened beverages and cancer mortality. “This study is one of the few that looks at the prognosis of women with breast cancer with respect to non-diet soda consumption,” Koyratty says.

Researchers assessed the relationship between sugar-sweetened soda and both all-cause and breast cancer mortality among 927 women who had been diagnosed with breast cancer, aged 35 to 79. Participants were enrolled in the Western New York Exposures and Breast Cancer (WEB) Study, and followed for a median of nearly 19 years.

The study used a food frequency questionnaire to assess participants’ food and beverage intake in the 12 to 24 months prior to diagnosis of breast cancer. Of the more than 900 women diagnosed with breast cancer, 41% had died by the end of the follow-up period. Among the participants who had died, there was a higher percentage of women who reported high frequency of sugar-sweetened soda consumption compared to the women who were still living.

The associations did not change when researchers included diet soda consumption as a variable.

Why the focus on non-diet soda?

“Non-diet sodas are the highest contributors of sugar and extra calories to the diet, but they do not bring anything else that is nutritionally beneficial,” Koyratty explains. “On the other hand, teas, coffees and 100% fruit juices, unless sugars are added, are healthier beverage options because they do add to the nutritive value through antioxidants and vitamins.”

Sugar-sweetened sodas contain large quantities of sucrose and fructose, which give them the highest glycemic load compared to other foods or beverages. These higher concentrations of glucose and insulin may lead to conditions that have been associated with higher risk of breast cancer, the researchers note.

“There are more than 3.5 million breast cancer survivors alive in the U.S. today. We need to better understand the factors that affect their health,” said study senior author Jo L. Freudenheim, Ph.D., SUNY Distinguished Professor in the Department of Epidemiology and Environmental Health in UB’s School of Public Health and Health Professions.

“While we need more studies to confirm our findings, this study provides evidence that diet may impact longevity of women after breast cancer,” Freudenheim added.

In decision-making, biases are an unconscious tendency that are difficult to eradicate

University of Pompeu Fabra and New York University, March 10, 2021

Often, humans display biases, i.e., unconscious tendencies towards a type of decision. Despite decades of study, we are yet to discover why biases are so persistent in all types of decisions. “Biases can help us make better decisions when we use them correctly in an action that has previously given us great reward. However, in other cases, biases can play against us, such as when we repeat actions in situations when it would be better not to”, says Rubén Moreno Bote, coordinator of the UPF Theoretical and Cognitive Neuroscience Laboratory.

In these cases, decisions are guided by tendencies, or inclinations, that do not benefit our wellbeing. For example, playing the lottery more regularly after winning a small consolation prize is a common bias that unfortunately does not tend to improve our financial situation.

The aim of the research was to establish how biases arise in decision-making using mathematical models and neural recordings

A study led by professor Rubén Moreno Bote’s laboratory, with Grabriela Mochol, researchers at the Center for Brain and Cognition (CBC) at the UPF Department of Information and Communication Technologies (DTIC), in collaboration with the experimental laboratory of professor Roozbeh Kiani of New York University (USA), has studied how biases arise in decision-making using mathematical models and neural recordings in primates. The study was published by the authors on 26 February in the journal Current Biology.

A task dealing with the perception of visual stimuli

The experimental block of the study consisted of a visual perception task in which a monkey observed a certain stimulus, specifically moving dots. The primate had to decide whether there were more dots moving to the right or to the left. Trial after trial, the animal performed this monotonous decision-making process.

The authors found that primate developed two types of bias: a “slow” tendency to indicate right (or left) that lasted several minutes, despite not having any net tendency in the set of stimuli used, and a “fast” tendency that lasted scarcely a few seconds, resulting from the actions had just been made in the previous decision.

The neural representation of biases is similar to the neural representation of relevant information for solving a certain task

“For this research, we study how the prefrontal cortex, which is crucial in decision-making, encodes the two identified biases (slow and fast). The main result of the study shows that the neural representation of biases is similar to the neural representation of relevant information for solving a certain task. This would seem to indicate that the format in which biases and information are coded in the brain are very similar, so similar that it is difficult to distinguish them”, points out Moreno Bote, study principal investigator.

And he adds: “We still have much to understand, but the results of this research could explain why biases are so prevalent in decision-making, and why, much to our regret, they are so difficult to eradicate”.