The Gary Null Show - 03.22.21

Choline supplements may help delay dementia in APOE4 gene carriers

MIT and National Institute of Diabetes and Digestive and Kidney Diseases, March 18, 2021

 

Researchers found that the APOE4 gene may increase the risk of developing Alzheimer's disease and other dementias by altering brain cells' lipid metabolism.

Choline supplements reversed these defects in cell studies, supporting further research in people carrying APOE4.

Certain genes can increase the risk of developing dementia, including Alzheimer's disease. One of the most significant genetic risk factors is a form of the apolipoprotein E gene called APOE4. About 25% of people carry one copy of APOE4, and 2 to 3% carry two copies. ApoE4 is the strongest risk factor gene for Alzheimer's disease, although inheriting ApoE4 does not mean a person will definitely develop the disease.

The APOE gene comes in several different forms, or alleles. APOE3 is the most common and not believed to affect Alzheimer's risk. APOE2 is relatively rare and may provide some protection against Alzheimer's disease.

The reason APOE4 increases Alzheimer's risk isn't not well understood. The APOE protein helps carry cholesterol and other types of fat in the bloodstream. Recent studies suggest that problems with brain cells' ability to process fats, or lipids, may play a key role in Alzheimer's and related diseases.

Lipid imbalances can impair many of a cell's essential processes. This includes creating cell membranes, moving molecules within the cell, and generating energy.

Dr. Li-Huei Tsai and the late Dr. Susan Lindquist of MIT investigated how APOE4 affects lipid metabolism in brain cells. The study was funded by NIH's National Institute on Aging (NIA), National Cancer Institute (NCI), and National Institute of Neurological Disorders and Stroke (NINDS). Dr. Priyanka Narayan of NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) was a co-first author. Findings were published in Science Translational Medicine on March 3, 2021.

The research team began by creating brain cells called astrocytes using stem cells. They used skin cells from people carrying APOE3 or APOE4 that were reprogrammed into a state where they could develop into any cell. Called induced pluripotent stem cells, these cells were then coaxed into becoming astrocytes, star-shaped cells that produce the most ApoE in the brain.

The researchers found changes in how APOE4 astrocytes were able to process lipids. The astrocytes accumulated droplets containing fats called triglycerides. These triglycerides had many more unsaturated fatty acid chains than normal. Lipid buildup in the APOE4 astrocytes was much greater than in APOE3 astrocytes. The researchers also found disruptions in lipid metabolism when they coaxed the cells into becoming other brain cells called microglia.

The team next tested whether yeast cells with the human version of APOE4 would have the same disruption in lipid metabolism. Lipid metabolism pathways are very similar between yeast and humans. Yeast with a copy of the APOE4 gene accumulated lipids much like the human cells did. Genetic screens in the yeast identified a molecular pathway that could be responsible for the defects. Boosting the activity of a pathway that normally produces phospholipidsan essential building block of the cell membranereversed some of the lipid accumulation.

Further research showed that supplementing the yeast cells' culture with choline restored normal lipid metabolism. Choline is needed to synthesize phospholipids. Similar benefits were seen after treating the human APOE4 astrocyte cells with choline. These findings provide preliminary support for testing choline supplements in people who carry APOE4.

"What we would really like to see is whether in the human population, in those APOE4 carriers, if they take choline supplements to a sufficient amount, whether that would delay or give them some protection against developing dementia or Alzheimer's disease," Tsai says.

However, it is important to keep in mind that results from isolated cells don't often translate into successful approaches when tested in people.

 

 

Acupuncture Tops Usual Care for Pain in Cancer Survivors

Two types of acupuncture proved superior, with one better than the other

Memorial Sloan Kettering Cancer Center  March 18, 2021

 

Two types of acupuncture significantly reduced chronic musculoskeletal pain in cancer survivors as compared with usual care, a randomized trial showed.

Electroacupuncture reduced patient-reported pain by 1.9 points versus usual care, and auricular acupuncture reduced patients' mean pain score by 1.6 points as compared with usual care, which consisted of analgesics, physical therapy, and steroid injections.

Auricular acupuncture, developed by the U.S. military and widely used in VA health facilities, failed to achieve noninferiority to electroacupuncture and was associated with more adverse events (AEs), reported Jun J. Mao, MD, of Memorial Sloan Kettering Cancer Center in New York City, and co-authors in JAMA Oncology.

"The magnitude of effect of electroacupuncture was clinically important and durable," the authors wrote. "This finding is consistent with evidence from other large acupuncture trials for chronic pain in the general population. Electroacupuncture has been shown to influence endogenous opioid release, which provides a mechanistic basis for chronic pain management."

"The present trial includes a large and diverse group of cancer survivors and provides evidence that electroacupuncture provides additional benefits beyond usual care, including not only reduction in pain severity, but also improvements in physical function and quality of life and reductions in analgesic use."

The U.S. has a growing population of cancer survivors, who have a greater pain burden than the general population. Almost half of cancer survivors receive inadequate pain relief, adversely affecting quality of life, physical function, and cancer-related outcomes.

A large body of evidence supports the superiority of acupuncture over usual care for relief of chronic noncancer pain, and last year CMS approved coverage of acupuncture for chronic lower back pain. A recent meta-analysis showed that acupuncture reduced cancer-associated pain, but the strength of evidence was considered moderate because of trials' small sample sizes and heterogeneity of acupuncture techniques.

Mao and colleagues reported findings from the largest randomized trial to date of acupuncture for cancer-related pain. The multicenter PEACE study enrolled adults with a history of cancer but no current evidence of disease. Eligible patients had musculoskeletal pain for at least 3 months and at least 15 of the preceding 30 days and a worst pain intensity within the past week of ≥4 (moderate or greater) on the 0-10 scale of the Brief Pain Inventory (BPI).

Patients were randomized 2:2:1 to electroacupuncture, auricular acupuncture, or usual care. Licensed experienced acupuncturists provided both types of acupuncture. During electroacupuncture, needles were placed at four sites near the pain location and four additional sites elsewhere on the body to address comorbid symptoms. The angle and depth of insertion were individualized to each patient's body type and point location. Treatment consisted of 10 once-weekly 30-minute sessions.

The protocol for auricular acupuncture, often called "battlefield acupuncture," was standardized and began with insertion of one needle into the cingulate gyrus of one ear. The patient then walked for 1 minute. If pain remained ≥1 on the BPI, another needle was inserted into the other ear. The process was repeated for the remaining ear points: thalamus, omega 2, point zero, and shen men.

The primary endpoint was change in average BPI score from baseline to week 12, and data analysis included 360 patients. Of 145 patients randomized to electroacupuncture, 136 (93.8%) completed at least eight sessions, as did 117 of 143 (81.8%) patients assigned to auricular acupuncture.

Mean baseline BPI scores ranged from 5.0 to 5.6. The most common sites of pain across all three groups were lower back (27.8% to 36.6%), knee/leg (14.5% to 23.6%), and hip/thigh (11.0% to 12.5%). At week 12, mean BPI score had declined by 0.48 in the usual care group, 2.39 in the electroacupuncture group (P<0.001), and 2.03 in the auricular acupuncture group (P<0.001). The 0.36 difference between the two acupuncture groups exceeded the prespecified noninferiority margin of 0.657 for auricular versus electroacupuncture.

AEs in both acupuncture groups were mild or moderate. Bruising was the most common AE in the electroacupuncture group (10.3%), and ear pain was most common with auricular acupuncture (18.9%). Only one patient (0.7%) discontinued electroacupuncture because of an AE, as compared with 15 (10.5%) in the auricular acupuncture group (P<0.001).

 

 

High vitamin D levels may protect against COVID-19, especially for Black people

In a study of individuals tested for COVID-19, vitamin D levels above those traditionally considered sufficient were associated with a lower risk of COVID-19.

University of Chicago Medicine Center, March 19, 2021

A new research study at the University of Chicago Medicine has found that when it comes to COVID-19, having vitamin D levels above those traditionally considered sufficient may lower the risk of infection, especially for Black people.

The study, published March 19 in JAMA Open Network, retrospectively examined the relationship between vitamin D levels and likelihood of testing positive for COVID-19. While levels of 30 ng/ml or more are usually considered "sufficient," the authors found that Black individuals who had levels of 30 to 40 ng/ml had a 2.64 times higher risk of testing positive for COVID-19 than people with levels of 40 ng/ml or greater. Statistically significant associations of vitamin D levels with COVID-19 risk were not found in white people. The study looked at data from over 3,000 patients at UChicago Medicine who had had their vitamin D levels tested within 14 days before a COVID-19 test. 

The research team is now recruiting participants for two separate clinical trials testing the efficacy of vitamin D supplements for preventing COVID-19. 

This research is an expansion of an earlier study showing that a vitamin D deficiency (less than 20 ng/ml) may raise the risk of testing positive for COVID-19. In the current study, those results were further supported, finding that individuals with a vitamin D deficiency had a 7.2% chance of testing positive for the virus. A separate study recently found that over 80% of patients diagnosed with COVID-19 were vitamin D deficient. 

"These new results tell us that having vitamin D levels above those normally considered sufficient is associated with decreased risk of testing positive for COVID-19, at least in Black individuals," said David Meltzer, MD, PhD, Chief of Hospital Medicine at UChicago Medicine and lead author of the study. "This supports arguments for designing clinical trials that can test whether or not vitamin D may be a viable intervention to lower the risk of the disease, especially in persons of color." 

Meltzer was inspired to investigate this topic after seeing an article in early 2020 that found people with vitamin D deficiency who had randomly been assigned to receive vitamin D supplementation had much lower rates of viral respiratory infections compared to those who did not receive supplementation. He decided to examine data being collected at UChicago Medicine on COVID-19 to determine the role that vitamin D levels might be playing. 

"There's a lot of literature on vitamin D. Most of it has been focused on bone health, which is where the current standards for sufficient vitamin D levels come from," Meltzer explained. "But there's also some evidence that vitamin D might improve immune function and decrease inflammation. So far, the data has been relatively inconclusive. Based on these results, we think that earlier studies may have given doses that were too low to have much of an effect on the immune system, even if they were sufficient for bone health. It may be that different levels of vitamin D are adequate for different functions." 

Vitamin D can be obtained through diet or supplements, or produced by the body in response to exposure of the skin to sunlight. Meltzer noted that most individuals, especially people with darker skin, have lower levels of vitamin D; roughly half of the world's population has levels below 30ng/ml. "Lifeguards, surfers, those are the kinds of folks who tend to have more than sufficient vitamin D levels," he said. "Most folks living in Chicago in the winter are going to have levels that are well below that." 

While vitamin D supplements are relatively safe to take, excessive consumption of vitamin D supplements is associated with hypercalcemia, a condition in which calcium builds up in the blood stream and causes nausea, vomiting, weakness, and frequent urination. If left unchecked, it can further lead to bone pain and kidney stones. 

"Currently, the adult recommended dietary allowance for vitamin D is 600 to 800 international units (IUs) per day," said Meltzer. "The National Academy of Medicine has said that taking up to 4,000 IUs per day is safe for the vast majority of people, and risk of hypercalcemia increases at levels over 10,000 IUs per day." 

One of the challenges of this study is that it is currently difficult to determine exactly how vitamin D may be supporting immune function. "This is an observational study," said Meltzer. "We can see that there's an association between vitamin D levels and likelihood of a COVID-19 diagnosis, but we don't know exactly why that is, or whether these results are due to the vitamin D directly or other related biological factors." 

Prompted by the evidence that people with vitamin D deficiency are more likely to test positive for COVID-19 and experience significant symptoms, a team at the University of Chicago and Rush University is conducting two studies to learn whether taking a daily vitamin D supplement can help prevent COVID-19 or decrease the severity of its symptoms.

 

 

Study: 94% of older adults prescribed drugs that raise risk of falling

From 1999-2017, more than 7.8 billion fall-risk-increasing drugs were prescribed to older adults in the US, and deaths from falls doubled

University of Buffalo, March 2021 

Nearly every older adult was prescribed a prescription drug that increased their risk of falling in 2017, according to new University at Buffalo research.

The study found that the percentage of adults 65 and older who were prescribed a fall- risk-increasing drug climbed to 94% in 2017, a significant leap from 57% in 1999. The research also revealed that the rate of death caused by falls in older adults more than doubled during the same time period.

Even minor falls may be dangerous for older adults. Falls that are not fatal can still result in injuries - such as hip fractures and head traumas - that may drastically lower remaining quality of life. Each year, nearly $50 billion is spent on medical costs related to fall injuries among older adults, according to the Centers for Disease Control and Prevention.

The alarming results solidify the importance of interventions to de-prescribe potentially inappropriate drugs among older, frailer patients, says Amy Shaver, PharmD, lead investigator and postdoctoral associate in the UB School of Public Health and Health Professions.

"Our study indicates two trends increasing concurrently at a population level that should be examined at the individual level. Our hope is it will start more conversations on health care teams about the pros and cons of medications prescribed for vulnerable populations," says Shaver.

Additional investigators in the UB School of Pharmacy and Pharmaceutical Sciences include Collin Clark, PharmD, clinical assistant professor; David Jacobs, PharmD, PhD, assistant professor; Robert Wahler Jr., PharmD, clinical associate professor; and Mary Hejna, PharmD, pharmacy resident at Kaleida Health.

Recently published in Pharmacoepidemiology and Drug Safety, the study examined data on deaths due to falls and prescription fills among people 65 and older from the National Vital Statistics System and the Medical Expenditure Panel Survey.

Fall-risk-increasing drugs include antidepressants, anticonvulsants, antipsychotics, antihypertensives (for high blood pressure), opioids, sedative hypnotics, and benzodiazepines (tranquilizers such as Valium and Xanax), as well as other nonprescription medications.

From 1999-2017, more than 7.8 billion fall-risk-increasing drug orders were filled by older adults in the United States. The majority of the prescriptions were for antihypertensives. However, there was also a sharp rise in the use of antidepressants, from 12 million prescriptions in 1999 to more than 52 million in 2017.

"The rise in the use of antidepressant medications seen in this study is likely related to the use of these agents as safer alternatives to older medications for conditions such as depression and anxiety," says Shaver. "However, it is important to note that these medications are still associated with increased risks of falls and fractures among older adults."

Women were also found more likely than men to be prescribed fall-risk-increasing drugs, particularly Black women, who received the medications at the highest rate compared to women of other races. White women who were 85 and older experienced the largest increase in deaths from falls, rising 160% between 1999 and 2017.

The investigators are involved in multidisciplinary de-prescribing initiatives conducted through Team Alice and the UB Center for Successful Aging. The efforts encourage and evaluate patient/caregiver-initiated de-prescribing conversations with health care providers, promote interprofessional education on de-prescribing, and advocate for policy and system changes.

 

Probiotic effective in treating gum inflammation: Study

University of Strasbourg (Germany), March 21, 2021

Probiotics can benefit inflammation of the tissue around the teeth, a meta-analysis suggests.

The authors found that periodontitis, which is usually treated with antibiotics, responded positively to the Lactobacillus reuteri probiotic species providing a viable alternative and lowering antibiotic resistance risk.

The antibiotics commonly used in periodontal treatment are penicillin, tetracycline, macrolide and metronidazole and microbiota of the oral cavity can act as a reservoir of antibiotic-resistant microorganisms, some of which are capable of causing disease.

Currently, in Europe , China, and the United States, periodontitis is reported to affect more than half of the adult population.

In ageing populations, the prevalence of periodontitis is even higher, with 70–90% of individuals aged between 60 and 74 suffering from the malady.

Review methodology

Researchers from the University of Strasbourg began by searching electronic databases.

Randomised controlled trials (RCTs) comparing scale and root planning (SRP) with probiotic treatment vs SRP were included.

A meta-analysis of these database results showed that the use of the probiotic supplement resulted in reduced values that measured the severity of periodontitis (PPD), improvements in measures of clinical manifestation and determinant of periodontal disease (CAL) and reduced bleeding on probing (BOP) in the short term.

“Certain probiotics could be used in combination with SRP for the management of chronic periodontitis, especially in case of deep pockets, with similar results to other adjunctive methods,” the authors noted.

The use of probiotics to accompany SRP has long been suggested as a better decontamination of the root surfaces alongside more first-line treatments such as antibiotics, antiseptics or photodynamic therapy.

Probiotic species such as Lactobacillius or Bifidobacterium are commonly used to treat diseases related to the gastrointestinal tract, as well as urogenital infections, eczema and oro-pharyngeal infections.

At the periodontal level, the application of probiotics in combination with SRP had been previously studied in animal models and produced evidence of delayed and reduced periodontopathogen recolonisation.  

“The most described probiotic regarding CP treatment is L. reuteri, a bacterium able to produce an antimicrobial compound resistant to proteolytic and liplytic enzymes. L.reuteri has shown in vitro an inhibitory effect against periodontopathogenic bacteria,” the study observed.

Conflicting studies

While the influence of L. reuteri on the reduction of gingival inflammation and plaque accumulation had been evaluated in several studies, there were some discrepancies among the results.

One study concluded that L. reuteri reduced both gingivitis and plaque in patients with moderate to severe ginigivitis in 14 days. However, in another study no significant differences in plaque index (PI) or gingival index (GI) were found at 8 weeks between test and control groups

 

 

Health declining in Gen X and Gen Y, national study shows

Ohio State University, March 20, 2021

Recent generations show a worrying decline in health compared to their parents and grandparents when they were the same age, a new national study reveals.

Researchers found that, compared to previous generations, members of Generation X and Generation Y showed poorer physical health, higher levels of unhealthy behaviors such as alcohol use and smoking, and more depression and anxiety.

The results suggest the likelihood of higher levels of diseases and more deaths in younger generations than we have seen in the past, said Hui Zheng, lead author of the study and professor of sociology at The Ohio State University.

"The worsening health profiles we found in Gen X and Gen Y is alarming," Zheng said.

"If we don't find a way to slow this trend, we are potentially going to see an expansion of morbidity and mortality rates in the United States as these generations get older."

Zheng conducted the study with Paola Echave, a graduate student in sociology at Ohio State. The results were published online yesterday (March 18, 2021) in the American Journal of Epidemiology.

The researchers used data from the National Health and Nutrition Examination Survey 1988-2016 (62,833 respondents) and the National Health Interview Survey 1997-2018 (625,221 respondents), both conducted by the National Center for Health Statistics.

To measure physical health, the researchers used eight markers of a condition called metabolic syndrome, a constellation of risk factors for heart disease, stroke, kidney disease and diabetes. Some of the markers include waist circumference, blood pressure, cholesterol level and body mass index (BMI). They also used one marker of chronic inflammation, low urinary albumin, and one additional marker of renal function, creatinine clearance.

The researchers found that the measures of physical health have worsened from the baby boomer generation through Gen X (born 1965-80) and Gen Y (born 1981-99). For whites, increases in metabolic syndrome were the main culprit, while increases in chronic inflammation were seen most in Black Americans, particularly men.

"The declining health trends in recent generations is a shocking finding," Zheng said. "It suggests we may have a challenging health prospect in the United State in coming years."

Zheng said it is beyond the scope of the study to comprehensively explain the reasons behind the health decline. But the researchers did check two factors. They found smoking couldn't explain the decline. Obesity could help explain the increase in metabolic syndrome, but not the increases seen in chronic inflammation.

It wasn't just the overall health markers that were concerning for some members of the younger generations, Zheng said.

Results showed that levels of anxiety and depression have increased for each generation of whites from the War Babies generation (born 1943-45) through Gen Y.

While levels of these two mental health indicators did increase for Blacks up through the early baby boomers, the rate has been generally flat since then.

Health behaviors also show worrying trends.

The probability of heavy drinking has continuously increased across generations for whites and Black males, especially after late-Gen X (born 1973-80).

For whites and Blacks, the probability of using street drugs peaked at late boomers (born 1956-64), decreased afterward, then rose again for late-Gen X. For Hispanics, it has continuously increased since early-baby boomers.

Surprisingly, results suggest the probability of having ever smoked has continuously increased across generations for all groups.

How can this be true with other research showing a decline in overall cigarette consumption since the 1970s?

"One possibility is that people in older generations are quitting smoking in larger numbers while younger generations are more likely to start smoking," Zheng said. "But we need further research to see if that is correct."

Zheng said these results may be just an early warning of what is to come.

"People in Gen X and Gen Y are still relatively young, so we may be underestimating their health problems," he said. "When they get older and chronic diseases become more prevalent, we'll have a better view of their health status."

Zheng noted that the United States has already seen recent decreases in life expectancy and increases in disability and morbidity.

"Our results suggest that without effective policy interventions, these disturbing trends won't be temporary, but a battle we'll have to continue to fight."

 

 

Why Black is the New Green Tea

Life Extension, March 19, 2021

We’ve been drinking green tea for years, and with good reason. Not only does it make for a tasty teatime, but study after study has demonstrated the protective effects of the antioxidants that green tea is loaded with, leading many of us to also take it in extract form. But have we been missing out by giving black tea the shrug off? As it turns out, black tea contains theaflavins, which have health benefits in their own right. Here’s how the two tea varieties compare.

What’s so great about green tea?

So why has green tea been a favorite for so many years? Green tea is loaded with antioxidants, which are potent age-fighting nutrients that protect cells and tissues from destruction caused by free radicals. Produced from environmental toxins, free radicals attack healthy cells and increase inflammation throughout your body, causing irreversible damage. Antioxidants in green tea gobble up those free radicals and reduce inflammation, keeping your cells safe and healthy.

Among other benefits, green tea has been shown to:

• Protect against heart disease
• Support the immune system
• Enhance mood and memory
• Relieve arthritis
• Help manage blood sugar

But green tea has its limits. It can't stop the production of free radicals or prevent inflammation from starting in the first place. That’s where black tea comes in.

Welcome to the dark side: the benefits of black tea

Might black tea be better for you than green tea? If longevity is your game plan, the answer is: perhaps. By influencing the expression of certain genes, black tea can prevent the production of free radicals and stop inflammation before it even starts, thanks to compounds called theaflavins.

Preclinical evidence shows that theaflavins, which give the tea its reddish hue, may protect against a huge array of different threats to our health, including cancer, atherosclerosis, obesity, osteoporosis, periodontal disease, inflammatory disorders and bacterial and viral infections.

Black tea and inflammation

Much of the misery of age-related conditions such as cardiovascular disease, diabetes, chronic pain and even cancer can be traced to inflammation. Chronic inflammation saturates your body in molecules known as cytokines, which are used by immune system cells to signal each other and react to potential threats. Circulating inflammatory cytokines have been linked to arterial disease, heart failure, atrial fibrillation, stroke and coronary heart disease, among other serious concerns.2,3

These inflammatory molecules are the products of specific genes, and black tea theaflavins can turn those genes off, helping to control inflammation when and where it starts.

Highly purified theaflavin extracts have been shown to reduce damage caused by inflammation-based diseases, such as:

• Cancer
• Cardiovascular disease
• Diabetes
• Arthritis
• Inflammatory bowel disease

Black or green, tea is a healthy choice

Both black and green tea have health benefits, whether you’re seeking the healthy mood and inflammatory response of green tea or want to address the genes involved in inflammation at their source with theaflavins from black tea. Since inflammation is the common denominator of all chronic age-related diseases, drink up! Or, seek a black tea or green tea based extract to add to your longevity regimen.