Dietary cocoa improves health of obese mice; likely has implications for humans
Penn State University, April 14, 2021
Supplementation of cocoa powder in the diet of high-fat-fed mice with liver disease markedly reduced the severity of their condition, according to a new study by Penn State researchers, who suggest the results have implications for people.
Cocoa powder, a popular food ingredient most commonly used in the production of chocolate, is rich in fiber, iron and phytochemicals reported to have positive health benefits, including antioxidant polyphenols and methylxanthines, noted study leader Joshua Lambert, professor of food science in the College of Agricultural Sciences.
“While it is typically considered an indulgence food because of its high sugar and fat content, epidemiological and human-intervention studies have suggested that chocolate consumption is associated with reduced risk of cardio-metabolic diseases including stroke, coronary heart disease and Type 2 diabetes,” Lambert said. “So, it made sense to investigate whether cocoa consumption had an effect on non-alcohol-related fatty liver disease, which is commonly associated with human obesity.”
This study has several strengths, Lambert explained. It used a commercially available cocoa product at a “physiologically achievable dose” — meaning its equivalent could be duplicated by humans. “Doing the calculations, for people it works out to about 10 tablespoons of cocoa powder a day,” he said. “Or, if you follow the directions on the Hershey’s box of cocoa powder, that’s about five cups of hot cocoa a day.”
The high-fat-fed mouse is a well-established, diet-induced model of obesity, Lambert added. By waiting until mice were already obese before beginning cocoa treatment, researchers were able to test the protective effects of cocoa in a model that better simulates the current public health situation related to non-alcohol-related fatty liver disease.
That’s important, Lambert pointed out, because a significant proportion of the world’s population has preexisting obesity and non-alcohol-related fatty liver disease. “Given the high proportion of people in the United States and other parts of the world with obesity, there is a need to develop potentially effective dietary interventions rather than just preventive agents,” he said.
For this study, researchers examined changes in fatty liver disease, markers of oxidative stress, antioxidant response and cell damage in high-fat-fed obese mice treated with a diet supplemented with 80 mg cocoa powder per gram of food — roughly a pinch per quarter teaspoon — for eight weeks.
In findings recently published in the Journal of Nutritional Biochemistry, the researchers reported that cocoa-treated mice gained weight at a 21% lower rate and had smaller spleen weights — indicating less inflammation — than the high-fat-fed control mice. At the end of the study, mice fed the cocoa-powder-supplemented diet had 28% less fat in their livers than the control mice. Cocoa-treated mice also had 56% lower levels of oxidative stress and 75% lower levels of DNA damage in the liver compared to high-fat-fed control mice.
The mechanisms by which cocoa imparts health benefits are not well understood, but previous studies in Lambert’s lab showed that extracts from cocoa and some of the chemicals in cocoa powder can inhibit the enzymes that are responsible for digesting dietary fat and carbohydrate.
The result, he proposes, is that when mice get cocoa as part of their diet, these compounds in the cocoa powder prevent the digestion of dietary fat. When it can’t be absorbed, the fat passes through their digestive systems. A similar process may occur with cocoa in humans, he hypothesizes.
In view of this new information about cocoa powder, Lambert is not recommending that obese people — or anyone — simply add five cups of hot cocoa to their daily routine and change nothing else in their diet. But he does advise, based on what he has learned in this study, to consider substituting cocoa for other foods, particularly high-calorie snack foods.
“This exchange is potentially beneficial, especially in combination with a healthy overall diet and increased physical activity,” he said. “If you go to the gym and work out, and your reward is you go home and have a cup of cocoa, that may be something that helps get you off the couch and moving around.”
Accelerated cellular aging associated with mortality seen in depressed individuals
Walter Reed Army Institute & University of California San Francisco, April 9, 2021
Cells from healthy individuals with major depressive disorder were found to have higher than expected rates of methylation at specific sites on their DNA, when compared to cells from healthy individuals without MDD, according to a study by a multidisciplinary team of Walter Reed Army Institute of Research and University of California San Francisco scientists, in collaboration with others.
Methylation is a process by which DNA is chemically modified at specific sites, resulting in changes in the expression of certain genes. Methylation of particular sets of genes, called “DNA methylation clocks,” typically change in predictable ways as people age, but the rate of these changes varies between people. Methylation patterns in individuals with MDD suggested that their DNA methylation cellular age was, on average, accelerated relative to matched healthy controls.
In the study, published in Translational Psychiatry, blood samples from 49 individuals with MDD were compared to 60 healthy control subjects of the same chronological age using the ‘GrimAge’ clock–a mathematical algorithm designed to predict an individual’s remaining lifespan based on cellular methylation patterns. Individuals with MDD showed a significantly higher GrimAge score, suggesting increased mortality risk compared to healthy individuals of the same chronological age–an average of approximately two years on the GrimAge clock.
The individuals with MDD were unmedicated prior to the study and showed no outward signs of age-related pathology, as they and the healthy controls were screened for physical health before entry into the study. The methylation patterns associated with mortality risk persisted even after accounting for lifestyle factors like smoking and BMI. These findings provide new insight into the increased mortality and morbidity associated with the condition, suggesting that there is an underlying biological mechanism accelerating cellular aging in some MDD sufferers.
“This is shifting the way we understand depression, from a purely mental or psychiatric disease, limited to processes in the brain, to a whole-body disease,” said Katerina Protsenko, a medical student at UCSF and lead author of the study. “This should fundamentally alter the way we approach depression and how we think about it–as a part of overall health.”
MDD is one of the most prevalent health concerns globally. According to the World health Organization, some 300 million people (4.4% of the population) suffer from some form of depression. MDD is associated with higher incidence and mortality related to increased rates of cardiovascular disease, diabetes, and Alzheimer’s disease among sufferers.
“One of the things that’s remarkable about depression is that sufferers have unexpectedly higher rates of age-related physical illnesses and early mortality, even after accounting for things like suicide and lifestyle habits,” said Dr. Owen Wolkowitz, professor of psychiatry and a member of UCSF’s Weill Institute for Neurosciences, co-senior author of the study. “That’s always been a mystery, and that’s what led us to look for signs of aging at the cellular level.”
The researchers say that they don’t yet know if depression causes altered methylation in certain individuals, or if depression and methylation are both related to another underlying factor. It is possible that some individuals may have a genetic predisposition to produce specific methylation patterns in response to stressors, but this has not been well-studied. Alterations in methylation patterns have previously been observed in individuals with post-traumatic stress disorder.
“These findings will allow us to better understand the relationships between behavioral health disorders–for example, 60% of PTSD cases are co-morbid with MDD. Elucidating these mechanistic and biochemical underpinnings will improve efforts to develop targeted diagnostic and treatment strategies, ultimately improving patient care,” said Dr. Marti Jett, WRAIR chief scientist. Previous research from the group used GrimAge to study men with combat PTSD.
Moving forward, the researchers hope to determine whether pharmacological treatments or therapy may mitigate some methylation changes related to MDD in hopes of normalizing the cellular aging process in affected individuals before it advances. Also, although the “GrimAge” methylation clock has been associated with mortality in other populations, no studies have yet prospectively determined whether this methylation pattern also predicts mortality in MDD.
“As we continue our studies, we hope to find out whether addressing the MDD with anti-depressants or other treatments alters the methylation patterns, which would give us some indication that these patterns are dynamic and can be changed,” said Dr. Synthia Mellon, professor in the Department of Obstetrics, Gynecology and the Reproductive Sciences at UCSF and co-senior author of the study.
Master athletes have longer telomeres than age-matched nonathletes
Catholic University of Brasilia (Brazil), April 2, 2021
According to news reporting from Brasilia, Brazil, research stated, “The aim of this systematic review and meta-analysis was 1) to assess whether master athletes have longer telomeres than age-matched non-athletes and 2) discuss possible underlying mechanisms underlying telomere length preservation in master athletes. A literature search was performed in PubMed, Web of Science, Scopus and SPORTDiscus up to August 2020.”
The news correspondents obtained a quote from the research from the Catholic University of Brasilia, “Only original articles published in peer-reviewed journals that compared telomere length between master athletes and aged-matched non-athletes were included. Eleven studies fulfilled eligibility criteria and were included in the final analysis. Overall, 240 master athletes (51.9 +/- 7.5 years) and 209 age-matched non-athletes (50.1 +/- 9.1 years) were analyzed. Master athletes had been participating in high-level competitions for approximately 16.6 years. Pooled analyses revealed that master athletes had longer telomeres than aged-matched non-athletes (SMD=0.89; 95% CI=0.45 to 1.33; p<0.001). Master athletes showed lower pro oxidant damage (SMD=0.59; 95% CI=0.26 to 0.91; p<0.001) and higher antioxidant capacity (SMD=-0.46; 95% CI=-0.89 to-0.03; p=0.04) than age-matched non-athletes. Further, greater telomere length in master athletes is associated with lower oxidative stress and chronic inflammation, and enhanced shelterin protein expression and telomerase activity.”
According to the news reporters, the research concluded: “1) master athletes have longer telomeres than age-matched non-athletes, which may be the result of 2) lower levels of oxidative stress and chronic inflammation, and elevated shelterin expression and telomerase activity.”
This research has been peer-reviewed.
Total flavonoids of Astragalus Ameliorated Bile Acid Metabolism Dysfunction in Diabetes MellitusMacau University of Science and Technology (China), April 2021
Astragalus Radix is one of the common traditional Chinese medicines used to treat diabetes. However, the underlying mechanism is not fully understood. Flavones are a class of active components that have been reported to exert various activities. Existing evidence suggests that flavones from Astragalus Radix may be pivotal in modulating progression of diabetes. In this study, total flavones from Astragalus Radix (TFA) were studied to observe its effects on metabolism of bile acids both in vivo and in vitro. C57BL/6J mice were treated with STZ and high-fat feeding to construct diabetic model, and HepG2 cell line was applied to investigate the influence of TFA on liver cells. We found a serious disturbance of bile acids and lipid metabolism in diabetic mice, and oral administration or cell incubation with TFA significantly reduced the production of total cholesterol (TCHO), total triglyceride, glutamic oxalacetic transaminase (AST), glutamic-pyruvic transaminase (ALT), and low-density lipoprotein (LDL-C), while it increased the level of high-density lipoprotein (HDL-C). The expression of glucose transporter 2 (GLUT2) and cholesterol 7α-hydroxylase (CYP7A1) was significantly upregulated on TFA treatment, and FXR and TGR5 play pivotal role in modulating bile acid and lipid metabolism. This study supplied a novel understanding towards the mechanism of Astragalus Radix on controlling diabetes.
Bile acids are synthesized by hepatocytes and play a pivotal role in the digestion and absorption of lipids . Recent findings have indicated its role in modulating glucose metabolism and controlling progression of diabetes. Astragalus Radix is a common Chinese medicine used to treat diabetes , and a report has demonstrated that Astragalus Radix can regulate blood lipid and blood glucose levels in HFD-fed mice . Previously, we found active flavonoid components of Astragalus Radix have protective effects against diabetic damage in vitro [10–13], but its influence on bile acid metabolism was not studied. In the present study, we found that TFA could modulate metabolism of bile acid both in vivo and in vitro, and the potential mechanism was also studied.
In conclusion, we found in the present study that TFA ameliorated lipid and bile acid metabolism under diabetic settings, and regulation of FXR and TGR5 should contribute to its effects. Our present findings provide a new understanding on mechanism of Astragalus Radix against progression of diabetes.Suggestions for Combatting COVID-19 by Natural Means in the Absence of Standard Medical Regimens
Georgetown University Medical Center, April 1, 2021
At this point in time, the COVID-19 pandemic appears relentless with no end in sight. Dire predictions of a continuance for as long as an additional two years or more have been voiced. A beneficial vaccine appears to be a long way off. The current standard treatment based on hand washing, face masks, quarantines, and distancing have produced some beneficial progress, but have also brought on a multitude of psychological perturbations. These have been amplified in turn largely by an array of serious economic woes which make the bad situation even worse. Further, while the appearance of a scientifically accepted near 100% cure could end the alarming situation immediately, there are not any readily acceptable ones in plain sight that would satisfy the majority of experts.
In order to come close to finding a rational cure for COVID-19, more precise knowledge about this novel deadly virus must be forth coming. Much has been learned to date but suffice it to say much more is needed. One piece of important information gained recently concerns the individuals most susceptible to the worst outcomes from the virus. Repeated constantly is the fact that the most vulnerable group suffering the worst outcomes is the elderly. So, it goes that if you’re 65 years of age, you’re in trouble. Nevertheless, calm down, because those 75 years of age are even in far more trouble. Is it necessary to compare the problem at 85 years of age?
The one rejoinder to all of this is that the aforementioned elderly’s situation worsens considerably if they possess chronic maladies associated with aging. That last statement is the one comeback that is almost always mentioned in any discussion of the prognosis of COVID-19 in senior patients. In truth though, is this the major reason behind the frequently poor outcome in the elderly—debilitating health issues rather than aging itself? If so, healthy, fit mature individuals may not have that bad a prognosis all things considered. This possibility provides increased optimism. Simply, we can’t do much about aging. It is an unavoidable circumstance, but one can often do something about improving general health. While aging chronologically is unstoppable, aging physiologically can be mitigated and slowed within a proper setting.
This leads to what should be obvious. A feasible major solution is for the vulnerable to build up their overall health status to ward off the pathogen, mitigate the symptomatology, and/or prevent death from the virus. While such should be the goal in a normal lifestyle, it is even more imperative under current circumstances. With the possibility, perhaps the probability, that this pandemic could be long and drawn out, one must think of long-term regimens and remedies to battle the COVID-19 that themselves do essentially no harm.
Putting forward guidance concerning the present pandemic is somewhat difficult—more so in a background of insufficient scientifically proven information to do such. Obviously, with the emergence of this pandemic involving a new agent, there would be insufficient randomized, double-blinded, placebo driven studies present to rely upon. In this situation, however, it is our contention that there may be enough “reasonable background knowledge” to at least begin instituting measures that might prevent or mitigate COVID-19 infections. Suffice it to say, it seems logical to turn to experts in the field and discover under the current circumstance just what they are doing themselves. Enough information may be provided to allow the consumer to make rational choices for themselves.
As mentioned above, the tolerating principle behind any proposal based more on background knowledge than actual scientific facts is that the regimen do no harm and in this case over long stretches of time. A possible answer to consider is whether this could be accomplished by taking a “natural” approach to the situation? This is the method that will be discussed in this report. The suggested natural regimen considered here consists of two stages—one that could be referred to as “directly” antiviral and the other “indirect” to increase the overall health to mitigate the response to COVID-19 .
So, with trepidation, our suggested course of action will be described in more detail. Concerning the antiviral aspects, two safe, potential antivirals are offered to be taken on a daily basis—monolaurin and oil of oregano. These had been examined in the past concerning their effects on bacteria and fungi (1–3).
When the pandemic arose, Dr. Preuss dug into his files and found some preliminary in vitro work concerning their antiviral potential that had been performed but never published. Some success was discovered for both agents against the lipid encapsulated respiratory syncytial virus (RSV). A viral syncytial assay was established using a HEp-2 culture assay based on the concept that when an RSV infects human lung epithelial cells (monolayer), it replicates and invades the adjoining or surrounding cells. A syncytium is formed when infected cells fuze. These infected centers can be visually examined directly or with a phase contrast microscope. Accordingly, effects of oregano oil and monolaurin in comparison with Ribavirin, an antiviral drug on the infection and the development of syncytia were conducted
Monolayers of HEp-2 cells at 80% confluency (in duplicates) were infected with 50 mcl of 10−4 dilutions of the virus stock (approx. 6 × 102 PFU).
Similar to the effects of a drug, Ribavirin, both oregano and monolaurin were able to destroy the ability of the virus to produce syncytial formation. This strengthens the postulate that oregano and monolaurin can destroy lipid-encapsulated viruses.
Lipid encapsulation is mentioned for a specific reason. A major basis behind the effects of monolaurin and oregano has been postulated to be their ability to destroy the protective lipid encapsulation of organisms (1–9). Accordingly, because of the long-term safety records of these natural products, they seem to be reasonable agents to consider therapeutically in the absence of effective drugs.
Concerning the indirect approach to combatting COVID-19, one intriguing aspect mentioned previously is that many of the deceased viral victims had elements of the Metabolic Syndrome (obesity, diabetes, hypertension) which is promoted by insulin resistance. Hence, improving insulin resistance could theoretically provide a better situation to prevent and/or successfully control COVID-19, especially in the elderly. What is insulin resistance? In many people over time, organs such as muscle do not respond to insulin properly. To compensate for this, the body increases insulin release. This is frequently an ongoing process that can result in higher circulating levels of both glucose and insulin which are not ideal for our general health. Insulin resistance with hyperinsulinemia is commonly linked to a general condition of inflammation along with a compromised immune system (10, 11). Unfortunately, insulin resistance is more likely found in the elderly and may explain, at least in part, why the elderly population is especially prone to death from COVID-19.
The postulate is that victims could battle the virus more successfully in a healthy state with the best possible immune reaction. Fortunately, safe inexpensive natural products that can overcome insulin resistance and produce greater immunity are available. In regards to this, vitamin D3 is an “insulin sensitizer” and should be on the first line of defense for two very vital reasons: (1) it may overcome the ravages of insulin resistance and improves the immune system and (2) it has the potential to ameliorate the cytokine storm that is the primary cause of the deaths in the elderly and others with COVID-19 (12–14). A reasonable daily dose of vitamin D3 would be 10,000 IU. A good daily routine to favor optimal health might also include: 500 mg Vitamin C, 800 mcg trivalent chromium, 30 mg zinc glycinate and 1000 mg turmeric. These agents do much good to reduce general inflammation and strengthen the immune system (15).
A healthy body is the best means to avoid and/or combat the virus. Much still can be achieved by advancing general health and bolstering the defenses against viral devastation until standard proven scientifically regimens arrive on the scene.
Effects of tart cherry and its metabolites on aging and inflammatory conditions
University of Delaware, April 9, 2021
According to news reporting out of Newark, Delaware, research stated, “Inflammation is an underlying cause of or a contributing factor to a number of chronic conditions, including hypertension, insulin resistance, arthritis, and cognitive disorders. A chronic inflammatory state is also associated with aging.”
Our news journalists obtained a quote from the research from the University of Delaware, “Tart cherry (TC) has been extensively studied for its ability to prevent or treat inflammatory diseases and their associated risk factors. TC contains active compounds, including polyphenols that may contribute to its antioxidant and anti-inflammatory effects. Inflammatory signaling pathways regulate the recruitment of inflammatory cells important for the pathogenesis of disease. Whole TC, individual compounds, and their metabolites may be viable treatment options because they can target molecules involved in inflammatory pathways. In this review, the effectiveness of TC in reducing inflammatory markers associated with chronic diseases and the effects of the active compounds in TC and their metabolites on inflammatory pathways are discussed. The main polyphenols present in TC include cyanidins, kaempferol, quercetin, melatonin, neochlorogenic acid, chlorogenic acid, and 3-coumaroylquinic acid.”
According to the news editors, the research concluded: “Evidence supports an association between TC intake and reduced risk for inflammatory disease, which may be due to the effects of active compounds in TC on inflammatory pathways, such as NF-kappa B and mitogen-activated protein kinase.”
This research has been peer-reviewed.
Aluminum is intricately associated with the neuropathology of familial Alzheimer’s disease
Keele University (UK), April 9, 2021
This study builds upon two earlier published studies (Mold et al., 2020, Journal of Alzheimer’s Disease Reports) from the same group. The new data, also published in the Journal of Alzheimer’s Disease Reports, demonstrate that aluminum is co-located with phosphorylated tau protein, present as tangles within neurons in the brains of early-onset or familial Alzheimer’s disease (AD). “The presence of these tangles is associated with neuronal cell death, and observations of aluminum in these tangles may highlight a role for aluminum in their formation,” explained lead investigator Matthew John Mold, PhD, Birchall Centre, Lennard-Jones Laboratories, Keele University, Staffordshire, UK.
The earlier research highlighted widespread co-localization of aluminum and amyloid-β in brain tissue in familial AD. The researchers used a highly-selective method of immunolabelling in the current study, combined with aluminum-specific fluorescence microscopy. Phosphorylated tau in tangles co-located with aluminum in the brain tissue of the same cohort of Colombian donors with familial AD were identified. “It is of interest and perhaps significance with respect to aluminum’s role in AD that its unequivocal association with tau is not as easily recognizable as with amyloid-β. There are many more aggregates of aluminum with amyloid-β than with tau in these tissues and the latter are predominantly intracellular,” remarked co-author, Professor Christopher Exley.
Per Dr. George Perry, Editor-in-Chief of Journal of Alzheimer’s Disease, “Aluminum accumulation has been associated with Alzheimer’s disease for nearly half a century, but it is the meticulously specific studies of Drs. Mold and Exley that are defining the exact molecular interaction of aluminum and other multivalent metals that may be critical to formation of the pathology of Alzheimer’s disease.”
“The new data may suggest that the association of aluminum with extracellular senile plaques precedes that with intracellular aggregates of tau. These relationships with both amyloid-β and tau may account for the high levels of aluminum observed in the brain tissue of donors with familial AD versus those without a diagnosis of neurodegenerative disease,” said Dr Mold. “Tau and amyloid-beta are known to act in synergy to produce neurotoxicity in AD and our data provide new evidence for a role of aluminum in this process”.Physical inactivity is associated with a higher risk for severe COVID-19 outcomes: a study in 48,440 adult patients
Kaiser Permanente Medical Center
Objectives To compare hospitalisation rates, intensive care unit (ICU) admissions and mortality for patients with COVID-19 who were consistently inactive, doing some activity or consistently meeting physical activity guidelines.
Methods We identified 48 440 adult patients with a COVID-19 diagnosis from 1 January 2020 to 21 October 2020, with at least three exercise vital sign measurements from 19 March 2018 to 18 March 2020. We linked each patient’s self-reported physical activity category (consistently inactive=0–10 min/week, some activity=11–149 min/week, consistently meeting guidelines=150+ min/week) to the risk of hospitalisation, ICU admission and death after COVID-19 diagnosis. We conducted multivariable logistic regression controlling for demographics and known risk factors to assess whether inactivity was associated with COVID-19 outcomes.
Results Patients with COVID-19 who were consistently inactive had a greater risk of hospitalisation (OR 2.26; 95% CI 1.81 to 2.83), admission to the ICU (OR 1.73; 95% CI 1.18 to 2.55) and death (OR 2.49; 95% CI 1.33 to 4.67) due to COVID-19 than patients who were consistently meeting physical activity guidelines. Patients who were consistently inactive also had a greater risk of hospitalisation (OR 1.20; 95% CI 1.10 to 1.32), admission to the ICU (OR 1.10; 95% CI 0.93 to 1.29) and death (OR 1.32; 95% CI 1.09 to 1.60) due to COVID-19 than patients who were doing some physical activity.
Conclusions Consistently meeting physical activity guidelines was strongly associated with a reduced risk for severe COVID-19 outcomes among infected adults. We recommend efforts to promote physical activity be prioritised by public health agencies and incorporated into routine medical care.