The Gary Null Show

The Gary Null Show - 11.03.21

November 3, 2021

Supplementation with vitamins C and E associated with decreased risk of cognitive impairment, dementia

 CHU de Québec Research Center, November 1, 2021.


An article that appeared in the Annals of Pharmacotherapy reports an association between the intake of vitamin C and E supplements and a lower risk of developing cognitive decline among men and women aged 65 years and older.


The current investigation included 5,269 men and women who were free of dementia upon enrollment in the Canadian Study of Health and Aging from 1991 to 1992. Follow-up examinations conducted during 1996-1997 and 2001-2002 provided post-enrollment diagnoses of dementia or cognitive impairment without dementia. Information concerning current use of prescription drugs and vitamins was ascertained from interview or questionnaire responses at the beginning of the study.


Approximately 10% of the subjects reported using vitamin C or E. Over up to 11 years of follow up, 821 cases of all-cause dementia (including 560 Alzheimer’s disease cases) were diagnosed and 882 cases of cognitive impairment without dementia developed. In comparison with those who did not report supplementing with either vitamin, the use of vitamin C and/or vitamin E was associated with a 38% lower adjusted risk of all-cause dementia and a 40% lower risk of Alzheimer’s disease. For cognitive impairment without dementia, the risk was 23% lower among those who used either or both vitamins. Evaluation of the effects of using either vitamin alone resulted in associations with similar risk reductions.


 “This study supports a protective role of vitamin E and C supplements in the risk for Alzheimer’s disease and all-cause dementia,” authors Luta L. Basambombo, MSc, of CHU de Québec Research Center and colleagues conclude. “In addition, these supplements may contribute to a reduced risk of CIND [cognitive impairment, not dementia]. Overall, these findings indicate additional support for the use of antioxidants as a preventive strategy against cognitive decline.”




Research suggests calorie restriction may be better than keto for cancer patients

Massachusetts Institute of Technology, October 22 2021. 


Findings reported in Nature revealed that restricting the intake of calories, including fats, rather than adopting a regimen of restricted carbohydrates and increased fats as characterized by a ketogenic diet, was associated with slower tumor growth in mice. 

Evan Lien, PhD, and associates evaluated the effects of calorie restricted, ketogenic or normal diets in mice with pancreatic tumors. While both glucose and plasma and tumor lipid levels declined in calorie-restricted animals, ketogenic diet-fed mice had lower glucose levels, but an increase in lipids. 

In comparison with mice given ketogenic diets, slower tumor growth occurred in the calorie-restricted mice. The finding can be explained by the animals’ reduced levels of lipids, which are needed by cancer cells for membrane production. Diet-induced lipid depletion decreases cellular levels of polyunsaturated fatty acids because they can’t be manufactured by the body and must be obtained from food. When these lipids aren’t available, cells make their own in a process that requires the enzyme SCD, which converts saturated fatty acids into unsaturated fatty acids. Since both diets lowered SCD activity, mice that received calorie restricted diets couldn’t obtain enough fatty acids from their diet or produce their own, whereas animals on the ketogenic diet had abundant lipids. “Not only does caloric restriction starve tumors of lipids, it also impairs the process that allows them to adapt to it,” Dr Lien explained. “That combination is really contributing to the inhibition of tumor growth.” 

“The purpose of these studies isn’t necessarily to recommend a diet, but it’s to really understand the underlying biology,” Dr Lien stated. “They provide some sense of the mechanisms of how these diets work, and that can lead to rational ideas on how we might mimic those situations for cancer therapy.”




Widespread fast-food restaurants linked to higher rates of type 2 diabetes

New York University, November 1, 2021

An increasing number of studies suggest a link between a neighborhood's built environment and the likelihood that its residents will develop chronic diseases such as heart disease, type 2 diabetes (T2D) and certain types of cancers. A new nationwide study led by researchers from NYU Grossman School of Medicine published online today in JAMA Network Open suggests that living in neighborhoods with higher availability of fast-food outlets across all regions of the United States is associated with higher subsequent risk of developing type 2 diabetes.

Findings also indicated that the availability of more supermarkets could be protective against developing T2D, particularly in suburban and rural neighborhoods.

The study—notable for its large geographic breadth—uses data from a cohort of more than 4 million veterans living in 98 percent of U.S. census tracts across the country. It counted fast-food restaurants and supermarkets relative to other food outlets, and is the first, according to the researchers, to examine this relationship in four distinct types of neighborhoods (high-density urban, low-density urban, suburban, and rural) at the hyperlocal level nationwide.

"Most studies that examine the built food environment and its relationship to chronic diseases have been much smaller or conducted in localized areas," said Rania Kanchi, MPH, a researcher in the Department of Population Health at NYU Langone and lead author of the study. "Our study design is national in scope and allowed us to identify the types of communities that people are living in, characterize their food environment, and observe what happens to them over time. The size of our cohort allows for geographic generalizability in a way that other studies do not." 

How the study was conducted

The research team used data from the U.S. Veterans Health Administration (the largest single-payer healthcare system in the country) that captures more than 9 million veterans seen at more than 1,200 health facilities around the country. Using this data, the researchers then constructed a national cohort of more than 4 million veterans without diabetes from the VA electronic health records (EHR) between 2008 and 2016. Each veteran's health status was followed through 2018 or until the individual either developed diabetes, died, or had no appointments for more than two years.

Within each of four distinct neighborhood types, the proportion of restaurants that were fast food, and the proportion of food outlets that were supermarkets were tabulated within a one-mile walk in high- density urban neighborhoods, a two-mile drive in low-density urban neighborhoods, a six-mile drive in suburban communities, and a 10-mile drive in rural communities.

Veterans were followed for a median of five and a half years. During that time, 13.2 percent of the cohort were newly diagnosed with T2D. Males developed T2D more frequently than females (13.6 versus 8.2 percent). Non-Hispanic Black adults had the highest incidence (16.9 percent), compared to non-Hispanic Whites (12.9 percent), non-White Asian and Hispanics (12.8 percent), Native Hawaiian and Pacific Islanders (15 percent), and Native American and Alaskan Indians (14.2 percent).

When stratifying by community types, 14.3 percent of veterans living in high density urban communities developed T2D, while the lowest incidence was among those living in suburban and small town communities (12.6 percent).

Overall, the team concluded that the effect of the food environment on T2D incidence varied by how urban the community was, but did not vary further by region of the country.

"The more we learn about the relationship between the food environment and chronic diseases like type 2 diabetes, the more policymakers can act by improving the mix of healthy food options sold in restaurants and food outlets, or by creating better zoning laws that promote optimal food options for residents," said Lorna Thorpe, Ph.D., MPH, professor in the Department of Population Health at NYU Langone and senior author of the study.

One limitation of the study, according to the authors, is that the study may not be fully generalizable to non-veteran populations, as U.S. veterans tend to be predominantly male and have substantially greater health burdens and financial instability than the civilian population. They are also at greater risk of disability, obesity, and other chronic conditions.

The next phase of the research, say Thorpe and Kanchi, will be to better understand the impacts of the built environment on diabetes risk by subgroups. They plan to examine whether or not the relationships between fast-food restaurants, supermarkets and community types vary by gender, race/ethnicity, and socioeconomic status.


Researchers have discovered neurons needed for acupuncture's anti-inflammatory response

Harvard Medical School, October November 1, 2021

Acupuncture is a traditional Chinese technique that has been used for millennia to treat chronic pain and other health problems associated with inflammation, yet the scientific basis of the technique remains poorly understood.

Now, a team of researchers led by neuroscientists at Harvard Medical School has elucidated the underlying neuroanatomy of acupuncture that activates a specific signaling pathway.

In a study conducted in mice and published Oct. 13 in Nature, the team identified a subset of neurons that must be present for acupuncture to trigger an anti-inflammatory response via this signaling pathway.

The scientists determined that these neurons occur only in a specific area of the hindlimb region—thus explaining why acupuncture in the hindlimb works, while acupuncture in the abdomen does not.

"This study touches on one of the most fundamental questions in the acupuncture field: What is the neuroanatomical basis for body region, or acupoint, selectivity?" said lead investigator Qiufu Ma, HMS professor of neurobiology at Dana-Farber Cancer Institute.

One area of particular interest to the research team is the so-called cytokine storm—the rapid release of large quantities of cytokines that frequently drives severe, systemic inflammation, and can be triggered by many things, including COVID-19, cancer treatment, or sepsis.

"This exuberant immune response is a major medical problem with a very high fatality rate of 15 percent to 30 percent," Ma said. Even so, drugs to treat cytokine storm are lacking.

Adapting an ancient technique to treat aberrant inflammation

In recent decades, acupuncture has been increasingly embraced in Western medicine as a potential treatment for inflammation.

In this technique, acupoints on the body's surface are mechanically stimulated, triggering nerve signaling that affects the function of other parts of the body, including organs.

In a 2014 study, researchers reported that electroacupuncture, a modern version of traditional acupuncture that uses electrical stimulation, could reduce cytokine storm in mice by activating the vagal-adrenal axis—a pathway wherein the vagus nervesignals the adrenal glands to release dopamine.

In a study published in 2020, Ma and his team discovered that this electroacupuncture effect was region-specific: It was effective when given in the hindlimb region, but did not have an effect when administered in the abdominal region. The team hypothesized that there may be sensory neurons unique to the hindlimb region responsible for this difference in response.

In their new study, the researchers conducted a series of experiments in mice to investigate this hypothesis. First, they identified a small subset of sensory neurons marked by expression of the PROKR2Cre receptor. They determined that these neurons were three to four times more numerous in the deep fascia tissue of the hindlimb than in the fascia of the abdomen.

Then the team created mice that were missing these sensory neurons. They found that electroacupuncture in the hindlimb did not activate the vagal-adrenal axis in these mice. In another experiment, the team used light-based stimulation to directly target these sensory neurons in the deep fascia of the hindlimb.

This stimulation activated the vagal-adrenal axis in a manner similar to electroacupuncture. "Basically, the activation of these neurons is both necessary and sufficient to activate this vagal-adrenal axis," Ma said.

In a final experiment, the scientists explored the distribution of the neurons in the hindlimb. They discovered that there are considerably more neurons in the anterior muscles of the hindlimb than in the posterior muscles, resulting in a stronger response to electroacupuncture in the anterior region.

"Based on this nerve fiber distribution, we can almost precisely predict where electrical stimulation will be effective and where it will not be effective," Ma explained.

Together, these results provide "the first concrete, neuroanatomic explanation for acupoint selectivity and specificity," Ma added. "They tell us the acupuncture parameters, so where to go, how deep to go, how strong the intensity should be."

He noted that while the study was done in mice, the basic organization of neurons is likely evolutionarily conserved across mammals, including humans.

However, an important next step will be clinical testing of electroacupuncture in humans with inflammation caused by real-world infections such as COVID-19. Ma is also interested in exploring other signaling pathways that could be stimulated by acupuncture to treat conditions that cause excessive inflammation. 

"We have a lot of tough chronic diseases that still need better treatments," he said, such as inflammatory bowel syndrome and arthritis. Another area of need, he added, is excessive immune reactions that can be a side effect of cancer immunotherapy.

Ma hopes that his research will ultimately advance scientific understanding of acupuncture and provide practical information that can be used to improve and refine the technique.


Happy childhood memories linked to better health later in life

Michigan State University, November 5, 2018


People who have fond memories of childhood, specifically their relationships with their parents, tend to have better health, less depression and fewer chronic illnesses as older adults, according to research published by the American Psychological Association.

"We know that memory plays a huge part in how we make sense of the world—how we organize our past experiences and how we judge how we should act in the future. As a result, there are a lot of different ways that our memories of the past can guide us," said William J. Chopik, Ph.D., from Michigan State University and lead author of the study. "We found that good memories seem to have a positive effect on health and well-being, possibly through the ways that they reduce stress or help us maintain healthy choices in life."

The findings were published in the journal Health Psychology.

Previous research has shown a positive relationship between good memories and good health in young adults, including higher quality of work and personal relationships, lower substance use, lower depression and fewer health problems, according to Chopik. He and his co-author, Robin Edelstein, Ph.D., from the University of Michigan, Ann Arbor, wanted to see how this would apply to older adults.

Also, much of the existing research focused on mothers and rarely examined the role of fathers in child development. Chopik and Edelstein sought to expand on the existing studies to include participants' reflections of their relationships with both parents.

The researchers used data from two nationally representative samples, the National Survey of Midlife Development in the United States and the Health and Retirement Study, with a total of more than 22,000 participants. The first study followed adults in their mid-40s for 18 years and the second followed adults 50 and over for six years. The surveys included questions about perceptions of parental affection, overall health, chronic conditions and depressive symptoms.

Participants in both groups who reported remembering higher levels of affection from their mothers in early childhood experienced better physical health and fewer depressive symptoms later in life. Those who reported memories with more support from their fathers also experienced fewer depressive symptoms, according to Chopik.

"The most surprising finding was that we thought the effects would fade over time because participants were trying to recall things that happened sometimes over 50 years ago. One might expect childhood memories to matter less and less over time, but these memories still predicted better physical and mental health when people were in middle age and older adulthood," said Chopik.

There was a stronger association in people who reported a more loving relationship with their mothers, noted Chopik, but that might change.

"These results may reflect the broader cultural circumstances of the time when the participants were raised because mothers were most likely the primary caregivers," said Edelstein. "With shifting cultural norms about the role of fathers in caregiving, it is possible that results from future studies of people born in more recent years will focus more on relationships with their fathers."

Chopik and Edelstein found that participants with positive childhood memories also had fewer chronic conditions in the first study of 7,100 people, but not in the second study of 15,200, making the results less straightforward


Researchers outline the connection between inflammation and depression

Emory University, October 28, 2021

In a paper published recently in Pharmacological Reviews, Emory University School of Medicine researchers outlined the impact of inflammation on motivation as it relates to depression.

The researchers propose that low grade inflammation affects brain chemicals and brain circuits that regulate motivation, ultimately leading to motivational deficits and a loss of interest or willingness to engage in usually pleasurable activities including work and play. These motivational deficits are reflected as anhedonia, a core and likely the most disabling symptom of depression, as well as other psychiatric disorders.

The paper also outlines how these effects of inflammation on the brain are an adaptation to the energy demands of inflammation that require conservation of energy resources, and thus the shutting down of behavior. Low grade inflammation can be caused by lifestyle changes such as poor diet and sedentary behavior.

"A vicious cycle can occur where poor lifestyle habits lead to increased inflammation that in turn reduce the wherewithal or motivation to change those habits. Such a vicious cycle may be especially relevant during pandemic life when even greater energy resources are required to sustain healthy eating and physical activity," says Andrew H. Miller, MD, William P. Timmie Professor of Psychiatry and Behavioral Sciences, Emory University School of Medicine. Miller co-authored the paper, along with his colleagues in the Department of Psychology and the Emory Behavioral Immunology Program, where he serves as director.

Miller says novel treatment strategies to break this vicious cycle are currently under development. He and his colleagues raise the possibility of developing treatments specifically for the motivational deficits caused by inflammation, thus moving to a much more targeted approach to therapeutic development in psychiatry, as now seen in the oncology field, versus the current use of outdated and non-specific diagnostic categories of psychiatric disease such as "depression."

"We believe more therapies targeted to specific pathophysiologic pathways and symptoms will lead to better outcomes and more precision care. Non-specific therapies as represented by conventional antidepressants, which are still embraced by regulatory agencies, do not instill the confidence that a more personalized approach does. There is widespread interest in moving in this direction internationally," says Miller.

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