The Gary Null Show - 05.26.21

A natural food supplement may relieve anxiety

Weizmann Institute of Science, May 24, 2021

A natural food supplement reduces anxiety in mice, according to a new Weizmann Institute of Science study. The plant-derived substance, beta-sitosterol, was found to produce this effect both on its own and in synergic combination with an antidepressant known under the brand name Prozac. If these findings, published today in Cell Reports Medicine, are confirmed in clinical trials, they could point the way toward the use of beta-sitosterol as a treatment for relieving anxiety in humans.

Anxiety is not always a bad thing. In fact, in evolutionary terms, feeling anxious about potential threats is critical for survival because it helps us mount an appropriate response. That's precisely why developing antianxiety drugs is so challenging. The circuits for anxiety in the brain are closely related to those responsible for memory, awareness and other functions vital for handling danger, so scientists are on the lookout for compounds that can selectively suppress anxiety without causing unwanted side effects.

The starting point for the present study was research conducted several years ago in the lab of Prof. Mike Fainzilber in Weizmann's Biomolecular Sciences Department. Dr. Nicolas Panayotis and other lab members studied the roles of proteins that shuttle cargoes into the nuclei of nerve cells, and they discovered that in stressful situations, mice lacking a shuttling protein known as importin alpha-five showed less anxiety than the control mice. The researchers then checked how these 'calmer' mice differed from regular ones in terms of gene expression, and they identified a genetic signature of their calmness: about 120 genes with a characteristic pattern of expression in the hippocampus, one of the brain regions that regulate anxiety.

In the new study, Panayotis, now a senior intern in Fainzilber's lab, together with colleagues, searched an international genomic database for existing drugs or other compounds that might mimic the same gene expression signature. He identified five candidates and tested their effects on behavior in mice. That was how the researchers zeroed in on beta-sitosterol, a plant substance sold as a dietary supplement intended mainly to reduce cholesterol levels.

In a series of behavioral experiments, mice given beta-sitosterol showed much less anxiety than the controls. They were, for example, less fearful than the controls when placed in an illuminated enclosure, daring to walk into its brightly lit center, whereas regular mice were careful to stay on the darker periphery, avoiding the stress of the bright light. Moreover, the mice receiving beta-sitosterol did not exhibit any of the side effects that might be expected from antianxiety medications—their locomotion was not impaired, and they did not refrain from exploring novel stimuli.

Next, the researchers tested the effects of beta-sitosterol on mice when given in combination with fluoxetine, a drug belonging to the class of selective serotonin reuptake inhibitors, or SSRIs, and sold under the brand name Prozac, among others. The combination had a synergistic effect: Both beta-sitosterol and fluoxetine reduced the anxiety of mice at lower doses when given together, compared with the doses needed to produce the same effect when they were administered separately.

"One of the major problems with existing antianxiety medications is that they produce side effects, so if beta-sitosterol could help cut down the dosage of such medications, it might potentially also reduce the unwanted side effects," Panayotis says.

A great advantage of beta-sitosterol is that it is naturally present in a variety of edible plants, and it is thought to be safe, as it has been marketed for years as a nutraceutical. It is found in particularly large concentrations in avocados, but also in pistachios, almonds and other nuts, in canola oil, in various grains and cereals and more.

However, this does not mean that eating avocado can induce a calming effect, since it doesn't contain enough beta-sitosterol. "You'd need to eat avocado day and night to get the right dose—and you would be more likely to develop digestive problems than relieve your anxiety," Panayotis says.

The precise mechanism of beta-sitosterol's effect on anxiety remains to be revealed, but the scientists did find that the expression of several genes known to be activated in stressful situations was reduced in mice given the supplement. They also found that these mice had changes in the levels of certain metabolites and neurotransmitters in brain areas involved in anxiety.

Since the study focused on brain regions and neural pathways that are involved in regulating anxiety in both mice and humans, it is likely that the findings will apply to humans as well. This will, however, require further clinical testing.

As Fainzilber points out: "There's a need for a clinical trial to test the use of beta-sitosterol for reducing anxiety in humans. Until then, we recommend that people consult their physicians before taking the supplement for this purpose."

 

Benfotiamine, vitamin B derivative, intake associated with reduced progression of cognitive decline

Weil Cornell Medicine, May 20, 2021

A randomized phase II trial reported in 2020 in the Journal of Alzheimer’s Disease resulted in positive effects among individuals with amnestic mild cognitive impairment or mild Alzheimer’s dementia who were given capsules that contained benfotiamine, a derivative of thiamine (vitamin B1). 

The trial included 70 cognitively impaired men and women who received physical examinations and completed the Mini-Mental Status Exam (MMSE) prior to enrollment. Prospective candidates received positron emission tomography (PET)/CT scans of the brain to confirm the presence of amyloid plaques that are characteristic of Alzheimer disease) and other general blood tests, an electrocardiogram and neurological exam prior to enrollment. Screening tests commonly used to test for diabetes were also performed prior to enrollment, and participants were required to have a hemoglobin A1c (HbA1c) of less than 8% and/or a fasting glucose of less than 200 milligrams per deciliter to be enrolled in the trial.

APOE genotype was determined upon enrollment in the trial. The presence of one or two copies of the APOE4 variant of the APOE gene is associated with a greater risk of Alzheimer disease in comparison with APOE2 or APOE3.

Blood testing conducted at the beginning and end of the trial measured levels of vitamin B1 and advanced glycation end-products (AGEs), which are formed when fats or proteins react with sugar in the blood. (Research suggests that AGEs are predictive of long-term decline in cognition-related daily living performance in Alzheimer disease patients.) Participants also underwent fluorodeoxyglucose positron-emission tomography (FDG PET) at these time points to assess brain glucose utilization which, when reduced, is associated with cognitive decline. Cognitive tests, including the Alzheimer Disease Assessment Scale-Cognitive Subscale, Clinical Dementia Rating and others were administered at the beginning of the study and at varying time points thereafter. Participants received capsules containing 300 milligrams benfotiamine or a placebo twice daily for one year. 

At the end of the treatment period, thiamine levels were significantly elevated in the benfotiamine-intake group. The 12 month increase in Alzheimer Disease Assessment Scale-Cognitive Subscale scores (indicating increased cognitive dysfunction) was lower among those who received benfotiamine compared to the placebo group. Benfotiamine intake participants additionally experienced 77% less deterioration in Clinical Dementia Rating scores compared to the placebo group; however, the effect seen with benfotiamine was stronger among participants who did not have the APOE4 variant. Benfotiamine was also associated with a significant reduction in the increase in AGEs compared to the placebo, which again was stronger in noncarriers of APOE4. FDG PET data suggested that participants without APOE4 were more responsive to benfotiamine intake.

“Benfotiamine is safe and cost effective, and the results of this pilot study are encouraging, providing preliminary evidence of efficacy,” authors Gary E. Gibson of Weil Cornell Medicine and colleagues concluded. “Our next step is to propose a larger clinical trial appropriately powered to replicate our findings. We believe that further studies would be very valuable to determine whether benfotiamine may be helpful in delaying onset or treating Alzheimer disease.”

 

'45 is the new 50' as age for colorectal cancer screening is lowered

Dana Farber Cancer Institute, May 21, 2021

BOSTON - Prompted by a recent alarming rise in cases of colorectal cancer in people younger than 50, an independent expert panel has recommended that individuals of average risk for the disease begin screening exams at 45 years of age instead of the traditional 50. 

The guideline changes by the U.S. Preventive Services Task Force (USPSTF), published in the current issue of JAMA, updates its 2016 recommendations and aligns them with those of the American Cancer Society, which lowered the age for initiation of screening to 45 years in 2018.

Colorectal cancer (CRC) is one of the most preventable malignancies, owing to its long natural history of progression and the availability of screening tests that can intercept and detect the disease early. Overall incidence of CRC in individuals 50 years of age and older has declined steadily since the mid-1980s, largely because of increased screening and changing patterns of modifiable risk factors.

"A concerning increase in colorectal cancer incidence among younger individuals (ie, younger than 50 years; defined as young-onset colorectal cancer) has been documented since the mid-1990s, with 11% of colon cancers and 15% of rectal cancers in 2020 occurring among patients younger than 50 years, compared with 5% and 9%, respectively, in 2010," said Kimmie Ng, MD, MPH, first author of an editorial in JAMA accompanying the article about the guideline change of the USPSTF. Ng is the director of the Young-Onset Colorectal Cancer Center at Dana-Farber Cancer Institute. 

The causes of the increase in young-onset CRC aren't currently known. 

Lowering the recommended age to initiate screening "will make colorectal cancer screening, which is so important, available to millions more people in the United States, and hopefully many more lives will be saved by catching colorectal cancer earlier, as well as by preventing colorectal cancer," said Ng.

The USPSTF is an independent panel of experts funded by the U.S. Department of Health and Human Services. It systematically reviews the evidence of effectiveness of preventive services and develops recommendations. American health insurance groups are required to cover, at no charge to the patient, any service that the USPSTF recommends with a grade A or B level of evidence, regardless of how much it costs.

The task force recommendation means that insurers will be required to cover preventive procedures such as colonoscopies and stool tests designed to detect colon cancer in early stages.

The task force selected age 45 based on research showing that initiating screening at that age averted more early deaths than starting at age 50, with a relatively small increase in the number of colonoscopy complications. There is no change to the USPSTF 2016 recommendation to only selectively screen individuals aged 76 to 85, as research shows only small increases in life-years gained.

The accompanying JAMA editorial asked rhetorically whether the age of screening should be lowered even younger than age 45. While the majority of young-onset CRC diagnoses and deaths occurs in persons 45 to 49, the rate of increase in young-onset CRC is actually steepest in the very youngest patients. Colon cancer incidence is increasing by 2% per year in 20 to 29-year-olds, compared with 1.3% in 40 to 49-year-olds. Rectal cancer incidence is increasing by 3.2% per year in 20 to 29-year-olds and 30 to 39-year-olds, versus 2.3% in 40 to 49-year-olds.

"We are now seeing patients even younger than 45 - in their 20s and 30s - who are being diagnosed with this cancer and often at very late stages," said Ng. "Clearly the USPSTF recommendation to start screening at age 45 will not be enough to catch those young people who are being diagnosed."

Ultimately, optimal prevention and early detection of CRC in people younger than 45 will require further research into the underlying causes and risk factors of young-onset CRC, which have thus far remained elusive, said the editorial authors. 

The authors also called for "bold steps" to translate the lowered age of beginning screening into meaningful decreases in CRC incidence and mortality, noting that despite the preventive benefits of colorectal cancer screening, only 68.8 percent of eligible individuals in the United States undergo screening. The rate is lower among the uninsured and underinsured, those with low incomes, and racial and ethnic minorities. Barriers include lack of knowledge of the importance of screening, concerns about the invasive nature of colonoscopy, and lack of access to and provider recommendations for screening.

The editorial lists examples including public awareness campaigns, including those aimed at gaps in CRC incidence and mortality between Black and white Americans, and specific actions. Employers could provide 45-year-old employees with a paid "wellness day" to undergo CRC screening, or offer day care or transportation vouchers to overcome the logistical hurdles of colonoscopies. Health systems could offer weekend or after-hours appointments for colonoscopies.

The new recommendation "represents an important policy change," the authors wrote, "to drive progress toward reducing colorectal cancer incidence and mortality."

 

 

Study Finds New and Effective Treatment for Vitamin D Deficiency

Boston University School of Medicine, May 20, 2021

There are several million people worldwide with various fat malabsorption syndromes including those who have undergone gastric bypass surgery and those with obesity. These patients often have a difficult time absorbing vitamin D and both groups of patients are at an increased risk for vitamin D deficiency and therefore at higher risk for osteoporosis and osteomalacia (softening of the bones). Patients with obesity are also susceptible to vitamin D deficiency as vitamin D derived from intestinal absorption and cutaneous synthesis is diluted in a larger body pool of fat. Now a new study demonstrates 25-hydroxyvitamin D3 is an effective treatment for vitamin D deficiency for these specific patients.

According to the researchers, approximately one third of adults are obese and require much larger doses of vitamin D to satisfy their requirement. "This vitamin D metabolite is better absorbed in patients with fat malabsorption syndromes and since it is not as fat soluble, it does not gets diluted in the body fat and is effective in raising and maintaining blood levels of 25-hydroxyvitamin D in obese people," explained corresponding author Michael F. Holick, PhD, MD, professor of medicine, physiology and biophysics and molecular medicine at Boston University School of Medicine.

Healthy adults, adults with a fat malabsorption syndrome and obese adults were compared to evaluate if a more water-soluble form of vitamin D3 known as 25-hydroxyvitamin D3 was more effective than the same dose of vitamin D3 in improving their vitamin D status. The researchers observed that compared to healthy adults only about 36 percent of orally ingested vitamin D3 was found in the blood of patients with fat malabsorption syndromes including patients who had gastric bypass surgery. When the same adults ingested 25-hydroxyvitamin D3 the patients with fat malabsorption syndromes were able to absorb it as well as the healthy adults thereby raising their vitamin D status to the same degree. A similar observation was made in the obese subjects compared to the healthy controls. "Therefore using 25-hydroxyvitamin D3 could be a novel approach for treating vitamin D deficiency in patients with fat malabsorption syndromes and obese adults," added Holick.

Vitamin D deficiency not only results in bone loss increasing risk for fracture but causes the painful bone disease osteomalacia. Patients who are vitamin D deficient with osteomalacia have unrelenting achiness in their bones and muscles. Vitamin D deficiency has been associated with an increased risk of many chronic illnesses including multiple sclerosis, type 1 diabetes, heart disease, type 2 diabetes, depression, neurocognitive dysfunction and Alzheimer's disease as well as infectious diseases including COVID.

These findings appear online in the American Journal of Clinical Nutrition.

 

Young teens should only use recreational internet and video games one hour daily

Rutgers University, May 24, 2021

Middle-school aged children who use the internet, social media or video games recreationally for more than an hour each day during the school week have significantly lower grades and test scores, according to a study from the Center for Gambling Studies at Rutgers University-New Brunswick.

The findings appear in the journal Computers in Human Behavior. 

Researchers say the findings give parents and children a moderate threshold for using entertainment-related technology -- no more than one hour daily on school days and four hours a day on weekends. 

"Interactive technology is widely used to promote children's educational access and achievement," said lead author Vivien (Wen Li) Anthony, an assistant professor at the School of Social Work and research associate at the Rutgers Center for Gambling Studies. "During the COVID-19 pandemic, technology has been essential to facilitating remote learning. At the same time, there is a growing concern that excessive technology use, particularly for entertainment, may adversely affect children's educational development by facilitating undesirable study habits and detracting from time spent on learning activities." 

The researchers, which include Professor Lia Nower of the Rutgers Center for Gambling Studies and a researcher from Renmin University of China, analyzed the China Education Panel Survey data, a national survey of educational needs and outcomes of children in China. Approximately 10,000 first-year middle school students were surveyed and followed. Their average age was 13.5 years.

The results showed that children who used the internet, social media or video games for entertainment four or more hours daily were four times more likely to skip school than those who did not. Boys used interactive technology for entertainment significantly more than girls. Boys also performed worse and showed lower school engagement levels than girls.

"Such findings are critical, particularly in light of the recent movement toward online learning in countries throughout the world," said Anthony. "In a learning environment that integrates the internet, it is easy for children to move across educational and entertainment platforms during learning without alerting teachers or adults to alternate activities."

Anthony said children in the study who used technology in moderation (i.e., less than one hour per day on weekends) experienced less boredom at school, potentially due to the positive effects of participation in social media, video games and video streaming such as peer bonding and relationship building. Using interactive technology for entertainment in moderation advanced children's cognitive development. 

The findings suggest that parents place time limits on their children's interactive technology use, and that parents and teachers should help children to develop effective time management and self-regulation skills to reduce their reliance on technology.

 

Do people aged 105 and over live longer because they have more efficient DNA repair?

University of Bologna (Italy),  May 19, 2021

Researchers have found that people who live beyond 105 years tend to have a unique genetic background that makes their bodies more efficient at repairing DNA, according to a study published in eLife.

This is the first time that people with ‘extreme longevity’ have had their genomes decoded in such detail, providing clues as to why they live so long and manage to avoid age-related diseases.

“Aging is a common risk factor for several chronic diseases and conditions,” explains Paolo Garagnani, Associate Professor at the Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Italy, and a first author of the study. “We chose to study the genetics of a group of people who lived beyond 105 years old and compare them with a group of younger adults from the same area in Italy, as people in this younger age group tend to avoid many age-related diseases and therefore represent the best example of healthy aging.”

Garagnani and colleagues, in collaboration with several research groups in Italy and a research team led by Patrick Descombes at Nestle Research in Lausanne, Switzerland, recruited 81 semi-supercentenarians (those aged 105 years or older) and supercentenarians (those aged 110 years or older) from across the Italian peninsula. They compared these with 36 healthy people matched from the same region who were an average age of 68 years old.

They took blood samples from all the participants and conducted whole-genome sequencing to look for differences in the genes between the older and younger group. They then cross-checked their new results with genetic data from another previously published study which analysed 333 Italian people aged over 100 years old and 358 people aged around 60 years old.

They identified five common genetic changes that were more frequent in the 105+/110+ age groups, between two genes called COA1 and STK17A. When they cross-checked this against the published data, they found the same variants in the people aged over 100. Data acquired from computational analyses predicted that this genetic variability likely modulates the expression of three different genes.

The most frequently seen genetic changes were linked to increased activity of the STK17A gene in some tissues. This gene is involved in three areas important to the health of cells: coordinating the cell’s response to DNA damage, encouraging damaged cells to undergo programmed cell death and managing the amount of dangerous reactive oxygen species within a cell. These are important processes involved in the initiation and growth of many diseases such as cancer.

The most frequent genetic changes are also linked to reduced activity of the COA1 gene in some tissues. This gene is known to be important for the proper crosstalk between the cell nucleus and mitochondria - the energy-production factories in our cells whose dysfunction is a key factor in aging.

Additionally, the same region of the genome is linked to an increased expression of BLVRA in some tissues - a gene that is important to the health of cells due to its role in eliminating dangerous reactive oxygen species.

“Previous studies showed that DNA repair is one of the mechanisms allowing an extended lifespan across species,” says Cristina Giuliani, Senior Assistant Professor at the Laboratory of Molecular Anthropology, Department of Biological, Geological and Environmental Sciences, University of Bologna, and a senior author of the study. “We showed that this is true also within humans, and data suggest that the natural diversity in people reaching the last decades of life are, in part, linked to genetic variability that gives semi-supercentenarians the peculiar capability of efficiently managing cellular damage during their life course.”

The team also measured the number of naturally occurring mutations that people in each age group had accumulated throughout their life. They found that people aged 105+ or 110+ had a much lower burden of mutations in six out of seven genes tested. These individuals appeared to avoid the age-related increase in disruptive mutations, and this may have contributed in protecting them against diseases such as heart disease.

“This study constitutes the first whole-genome sequencing of extreme longevity at high coverage that allowed us to look at both inherited and naturally occurring genetic changes in older people,” says Massimo Delledonne, Full Professor at the University of Verona and a first author of the study.

“Our results suggest that DNA repair mechanisms and a low burden of mutations in specific genes are two central mechanisms that have protected people who have reached extreme longevity from age-related diseases,” concludes senior author Claudio Franceschi, Professor Emeritus of Immunology at the University of Bologna.

 

 

 

Your Risk of Dying Hinges on Well-Being Not Diseases

 

 

University of Chicago, May 18, 2021

A new study has yielded a radically different picture of aging in America, finding that how old you are plays little or no role in determining differences in health and well-being.

The researchers say the results suggest the medical community is focusing on the wrong set of factors to determine risk of dying. Rather than rely on a checklist of infirmities—heart disease, cancer, diabetes, high blood pressure, and cholesterol levels—perhaps it’s time to consider a new “comprehensive model” that looks at factors such as psychological well-being, sensory function, and mobility.

“The new comprehensive model of health identifies constellations of health completely hidden by the medical model and reclassifies about half of the people seen as healthy as having significant vulnerabilities that affect the chances that they may die or become incapacitated within five years,” says Professor Martha McClintock, a biopsychologist and lead author of the study in the Proceedings of the National Academy of Sciences.

“At the same time, some people with chronic disease are revealed as having many strengths that lead to their reclassification as quite healthy, with low risks of death and incapacity,” adds Professor Linda Waite, a demographer and study coauthor.

The study is a major longitudinal survey of a representative sample of 3,000 people between the ages of 57 to 85 conducted by the independent research organization NORC at the University of Chicago.

SOME OF THE FINDINGS INCLUDE:

• Cancer itself is not related to other conditions that undermine health.
• Poor mental health, which afflicts one in eight older adults, undermines healthin ways not previously recognized.
• Obesity seems to pose little risk to older adults with excellent physical and mental health.
• Sensory function and social participation play critical roles in sustaining or undermining health.
• Breaking a bone after age 45 is a major marker for future healthissues.
• Older men and women have different patterns of healthand well-being during aging.
• Mobility is one of the best markers of well-being.

The comprehensive model reflects a definition of health long advanced, but little studied, by the World Health Organization, which considers health to include psychological, social, and physical factors in addition to the diseases that are the basis for the current medical model of health.

THE HEALTHIEST 22%

Twenty-two percent of older Americans were in the model’s healthiest category. This group was typified by higher obesity and blood pressure, but had fewer organ system diseases, better mobility, sensory function, and psychological health. They had the lowest prevalence of dying or becoming incapacitated (six percent) five years into the study.

A second category had normal weight, low prevalence of cardiovascular disease and diabetes, but had one minor disease such as thyroid disease, peptic ulcers, or anemia. They were twice as likely to have died or become incapacitated within five years.

Two emerging vulnerable classes of health traits, completely overlooked by the medical model, included 28 percent of the older population. One group included people who had broken a bone after age 45. A second new class had mental health problems, in addition to poor sleep patterns, engaged in heavy drinking, had a poor sense of smell, and walked slowly, all of which correlate with depression.

The most vulnerable older people were in two classes—one characterized by immobility and uncontrolled diabetes and hypertension. A majority of people in each of these categories were women, who tend to outlive men.

“From a health system perspective, a shift of attention is needed from disease-focused management, such as medications for hypertension or high cholesterol, to overall well-being across many areas,” says William Dale, associate professor of medicine and a member of the research team.

“Instead of policies focused on reducing obesity as a much lamented health condition, greater support for reducing loneliness among isolated older adults or restoring sensory functions would be more effective in enhancing health and well-being in the older population,” says Edward Laumann, also a collaborator and sociology professor.