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Study explores effects of dietary choline deficiency on neurologic and system-wide health

Arizona State University, January 16, 2023

Choline, an essential nutrient produced in small amounts in the liver and found in foods including eggs, broccoli, beans, meat and poultry, is a vital ingredient for human health. A new study explores how a deficiency of dietary choline adversely affects the body and may be a missing piece in the puzzle of Alzheimer’s disease. It’s estimated that more than 90% of Americans are not meeting the recommended daily intake of choline. The current research, conducted in mice, suggests that dietary choline deficiency can have profound negative effects on the heart, liver and other organs. Lack of adequate choline is also linked with profound changes in the brain associated with Alzheimer’s disease. These include pathologies implicated in the development of two classic hallmarks of the illness: amyloid plaques, which aggregate in the intercellular spaces between neurons; and tau tangles, which condense within the bodies of neurons. The new research, led by scientists at Arizona State University and published in Aging Cell, describes pathologies in normal mice deprived of dietary choline and in choline-deficient transgenic mice, the latter of which already exhibit symptoms associated with the disease. In both cases, dietary choline deficiency results in liver damage, enlargement of the heart and neurologic alterations in the AD mice, typically accompanying Alzheimer’s disease and including increased levels of plaque-forming amyloid-beta protein and disease-linked alterations in tau protein. Further, the study illustrates that choline deficiency in mice causes significant weight gain, alterations in glucose metabolism (which are tied to conditions such as diabetes), and deficits in motor skills. In the case of humans, “it’s a twofold problem,” according to Ramon Velazquez, senior author of the study and assistant professor with the ASU-Banner Neurodegenerative Disease Research Center. “First, people don’t reach the adequate daily intake of choline established by the Institute of Medicine in 1998. And secondly, there is vast literature showing that the recommended daily intake amounts are not optimal for brain-related functions.” The research highlights a constellation of physical and neurological changes linked to choline deficiency. Sufficient choline in the diet reduces levels of the amino acid homocysteine, which has been recognized as a neurotoxin contributing to neurodegeneration, and is important for mediating functions such as learning and memory through the production of acetylcholine. The growing awareness of choline’s importance should encourage all adults to ensure proper choline intake. This is particularly true for those on plant-based diets, which may be low in naturally occurring choline, given that many foods high in choline are eggs, meats, and poultry. Plant-based, choline-rich foods, including soybeans, Brussels sprouts and certain nuts can help boost choline in these cases. Moreover, inexpensive, over-the-counter choline supplements are encouraged to promote overall health and guard the brain from the effects of neurodegeneration. The new study examines mice at 3-12 months, or early to late adulthood (roughly equivalent to 20-60 years of age for humans). In the case of both normal and transgenic mice displaying symptoms of Alzheimer’s, those exposed to a choline-deficient diet exhibited weight gain and adverse effects to their metabolism. Damage to the liver was observed through tissue analysis, as was enlargement of the heart. Elevated soluble, oligomeric and insoluble amyloid-beta protein were detected, as well as modifications to tau protein characteristic of those leading to neurofibrillary tangles in the brain. Further, choline-deficient mice performed poorly in a test of motor skills, when compared with mice receiving adequate choline in their diet. These adverse effects were heightened in the transgenic mice. Translating these findings to humans, this implies that people who are predisposed to Alzheimer’s disease or in the throes of the illness should ensure they are getting enough choline.”Our work provides further support that dietary choline should be consumed on a daily basis given the need throughout the body,” Velazquez says.

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Melanoma: Vitamin D supplements linked to reduced skin cancer risk

University of Eastern Finland & Kuopio University, January 15, 2023

A new study finds that the regular use of vitamin D is associated with lower rates of melanoma skin cancer. The cross-sectional study was a collaboration between the University of Eastern Finland and Kuopio University Hospital. The research involved 498 Finnish adults determined by dermatologists to be at high risk of skin cancer, such as melanoma, as well as squamous cell carcinoma and basal cell carcinoma. According to researchers, people who took vitamin D regularly were less likely to have had melanoma in the past or currently and were deemed by dermatologists to be less likely to develop melanoma in the future. Study participants ranged in age from 21 to 79 years old, including 253 males and 245 females. Participants were divided into three groups based on their intake of vitamin D supplements: non-use, occasional use, or regular use. The researchers were also interested in finding out whether regular use of vitamin D supplements corresponded to higher blood levels of vitamin D, known as serum calcidiol or 25-hydroxy-vitamin D3. This is the “storage form” of vitamin D in the body. Some research has linked low serum calcidiol with increased cancer risk, while other research has suggested otherwise. Nonetheless, it is a measure often used to determine a person’s vitamin D levels. After testing serum calcidiol levels in 260 participants, researchers found that regular vitamin D supplementation corresponded with the highest levels of serum calcidiol and non-supplementation with the lowest levels. “Human skin itself expresses [the enzyme] CYP27A1 that produces calcidiol from vitamin D, and CYP27B1 that produces biologically very active calcitriol from calcidiol,” Dr. Harvima explained, noting that enzyme expression determines the level of vitamin D and its metabolites in the body.

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New research furthers case for exercise promoting youthfulness

University of Arkansas, January 17, 2023

A recent paper published in the Journal of Physiology deepened the case for the youthfulness-promoting effects of exercise on aging organisms, building on previous work done with lab mice nearing the end of their natural lifespan that had access to a weighted exercise wheel. For this paper, the researchers compared aging mice that had access to a weighted exercise wheel with mice that had undergone epigenetic reprogramming via the expression of Yamanaka factors. The Yamanaka factors are four protein transcription factors (identified as Oct3/4, Sox2, Klf4 and c-Myc, often abbreviated to OKSM) that can revert highly specified cells (such as a skin cell) back to a stem cell, which is a younger and more adaptable state. The Nobel Prize in Physiology or Medicine was awarded to Dr. Shinya Yamanaka for this discovery in 2012. In the correct dosages, inducing the Yamanaka factors throughout the body in rodents can ameliorate the hallmarks of aging by mimicking the adaptability that is common to more youthful cells. Of the four factors, Myc is induced by exercising skeletal muscle. Myc may serve as a naturally induced reprogramming stimulus in muscle, making it a useful point of comparison between cells that have been reprogrammed via over expression of the Yamanaka factors and cells that have been reprogrammed through exercise—”reprogramming” in the latter case reflecting how an environmental stimulus can alter the accessibility and expression of genes. Ultimately, the team determined that exercise promotes a molecular profile consistent with epigenetic partial programming. That is to say, exercise can mimic aspects of the molecular profile of muscles that have been exposed to Yamanaka factors (thus displaying molecular characteristics of more youthful cells). This beneficial effect of exercise may in part be attributed to the specific actions of Myc in muscle. Murach sees their research as further validation of exercise as a polypill. “Exercise is the most powerful drug we have,” he says, and should be considered a health-enhancing—and potentially life-extending—treatment along with medications and a healthy diet.

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Exploiting the synergy of nutraceuticals for cancer prevention and treatment
Research suggests that free radicals (ROS) generated upon mixing two nutraceuticals—resveratrol and copper—can help ameliorate various diseases by inactivating cell-free chromatin particles

Tata Memorial Centre (India), January 16, 2023

Chromatin comprises a complex mixture of DNA and proteins that forms the structural basis of chromosomes in the cellular nuclei. When cells die, they release cell-free chromatin particles or “cfChPs” into the circulatory system. In 1996, evidence for tumour-derived DNA circulating in the blood of cancer patients was first reported. This evidence caught the interest Dr. Indraneel Mittra, who is now Professor Emeritus and the Dr. Ernest Borges Chair in Translational Research at Tata Memorial Centre in Mumbai, India. His tryst with research on genetic material in cancer metastases began, and after 15 years of research he has presented various papers, developing a body of evidence that indicates the critical role of cfChPs in orchestrating development of not only cancer, but various other diseases. Emerging evidence indicates that cfChPs play an essential role in ageing, sepsis, cancer development, and chemotherapy-related toxicity. With respect to the latter, Prof. Mittra explains, “Chemo-toxicity is not primarily caused by chemotherapeutic drugs, but rather by cfChPs that are released from the first cells that die after chemotherapy. The released cfChPs set in motion a cascading effect, increasingly damaging the DNA of healthy host cells, and triggering inflammatory processes in a vicious cycle that perpetuates and prolongs the toxicity of chemotherapy.” Recently, a team from Tata Memorial Centre have demonstrated the therapeutic benefits of a pro-oxidant mixture of resveratrol and copper, R-Cu, in patients undergoing chemotherapy for advanced gastric cancer. Combining R with Cu (R-Cu) leads to the generation of free oxygen radicals which can inactivate the offending cfChPs. In this context, the research team launched a single-arm phase II clinical trial to study the synergistic effects of R-Cu administration on cfChPs inactivation in patients with advanced gastric cancer. The primary objective was to determine whether R-Cu, via cfChPs’ inactivation, was successful in reducing the grade ≥ 3 toxicity seen with docetaxel-based chemotherapies. To this end, the researchers monitored the likely changes in the toxicities of chemotherapeutic treatments using a grading system that provides a framework for the assessment of unwanted physiological effects. The results were promising—although R-Cu did not reduce haematological toxicities, it significantly reduced the incidence of non-haematological toxicities comprising hand-foot syndrome, diarrhoea, and vomiting. Moreover, R-Cu reduced docetaxel exposure compared to the control arm without affecting efficacy in terms of overall survival.

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Deep meditation may alter gut microbes for better health

Shanghai Jiao Tong University School of Medicine (China), January 16, 2023

Regular deep meditation, practiced for several years, may help to regulate the gut microbiome and potentially lower the risks of physical and mental ill health, finds a small comparative study published in the open access journal General Psychiatry. The gut microbes found in a group of Tibetan Buddhist monks differed substantially from those of their secular neighbors, and have been linked to a lower risk of anxiety, depression, and cardiovascular disease. Research shows that the gut microbiome can affect mood and behavior through the gut–brain axis. This includes the body’s immune response, hormonal signaling, stress response and the vagus nerve—the main component of the parasympathetic nervous system, which oversees an array of crucial bodily functions. The significance of the group and specimen design is that these deep-thinking Tibetan monks can serve as representatives of some deeper meditations. Although the number of samples is small, they are rare because of their geographical location. The researchers analyzed the stool and blood samples of 37 Tibetan Buddhist monks from three temples and 19 secular residents in the neighboring areas. None of the participants had used agents that can alter the volume and diversity of gut microbes: antibiotics; probiotics; prebiotics; or antifungal drugs in the preceding 3 months. Sample analysis revealed significant differences in the diversity and volume of microbes between the monks and their neighbors.”Collectively, several bacteria enriched in the meditation group [have been] associated with the alleviation of mental illness, suggesting that meditation can influence certain bacteria that may have a role in mental health,” write the researchers. These include Prevotella, Bacteroidetes, Megamonas and Faecalibacterium species, the previously published research suggests. Finally, blood sample analysis showed that levels of agents associated with a heightened risk of cardiovascular disease, including total cholesterol and apolipoprotein B, were significantly lower in the monks than in their secular neighbors by their functional analysis with the gut microbes.

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Curcumin/Boswellia shows promise in chronic kidney disease

Baylor University, January 14, 2023.

The Journal of Complementary and Integrative Medicine reports the finding of researchers at Baylor University of a reduction in a marker of inflammation among chronic kidney disease patients given a combination of Curcuma longa (curcumin) and Boswellia serrata. The study included sixteen individuals receiving standard care for chronic kidney disease who were not undergoing dialysis. Participants were randomized to receive capsules containing curcumin from turmeric extract plus Boswellia serrata, or a placebo for eight weeks. Blood samples collected before and after treatment were analyzed for plasma interleukin-6 (IL-6), tumor necrosis factor alpha (markers of inflammation), and the endogenous antioxidant enzyme glutathione peroxidase, as well as serum C-reactive protein (CRP, another marker of inflammation.) Blood test results from the beginning of the study revealed increased inflammation and reduced glutathione peroxide levels. At the study’s conclusion, participants who received curcumin and Boswellia serrata experienced a reduction in interleukin-6 in comparison with pretreatment values, indicating decreased inflammation, while IL-6 values rose among those who received a placebo. In their discussion of the findings, the authors remark that curcumin and Boswellia serrata have been separately shown to lower interleukin-6 via inhibition of the nuclear factor kappa beta and mitogen activated protein kinase (MAPK) signaling pathways.