Science Digest – February 12, 2021 -pocket

Hi, Premium Members!

Here’s your Friday dose of happy – another awesome issue of the Science Digest.

In this issue we’ve covered a study showing that habitual use of supplemental vitamin D reduces the risk of developing COVID-19. And, because February is American Heart Month, we’ve covered three really interesting studies about nutritional strategies to treat heart failure, including magnesium, CoQ10, and NAD+. And lots more!

In other news…

We’ve got another Crowdcast live Q&A coming up Saturday, March 6th, at 9:30 am PDT. The code for this event is hormesis. Remember, you can always access the most recent event code and Q&A calendar by visiting your dashboard at

ICYMI: My February 6th Q&A has been uploaded to the members-only podcast feed (which you can find on the member’s dashboard). This was a great Q&A that covered a broad range of topics.


Rhonda and team
Science Digest – February 12, 2021
Regular use of supplemental vitamin D reduces the risk of developing COVID-19.

Vitamin D is a fat-soluble vitamin that plays key roles in several physiological processes, including immune function. Research indicates that people who take supplemental vitamin D are less likely to have acute respiratory tract infections. Findings from a new study suggest that regular use of supplemental vitamin D reduces the risk of developing COVID-19.

Vitamin D deficiency in the setting of COVID-19 can lead to over-expression of renin (an enzyme produced in the kidneys) and subsequent activation of the renin-angiotensin-system, a critical regulator of blood pressure, inflammation, and body fluid homeostasis. Disturbances in this system can drive poor outcomes in COVID-19.

The study involved nearly 8,300 adults enrolled in the UK Biobank study who had been tested for COVID-19. The investigators collected information about the participants’ demographics, health status, use of vitamin D supplements (as well as other vitamins), and circulating vitamin D levels.

The authors found that people who took vitamin D regularly (daily or weekly) tended to be older, have better overall health, and to take other supplements. They also had higher levels of circulating vitamin D. Notably, they were 34 percent less likely to develop COVID-19 compared to people who did not take vitamin D.

Although this was an observational study and causation cannot be established, these findings suggest that regular vitamin D supplementation is beneficial in reducing the risk of developing COVID-19. The authors posited that the protective effects of vitamin D are attributable to the vitamin’s capacity to maintain cell junctions to reduce the risk of infection; enhance cellular innate immunity; and modulate the renin-angiotensin-system.

Link to full study.

Supplemental magnesium ameliorates symptoms associated with heart failure.

Heart failure is commonly referred to as the end stage of heart disease – the culmination of all forms of cardiovascular disease. More than 26 million people worldwide have heart failure. Findings from a 2007 study suggested that supplemental magnesium ameliorates symptoms associated with heart failure.

Magnesium is an essential mineral and a cofactor for hundreds of enzymes. It is involved in many physiologic pathways, including energy production, protein synthesis, ion transport, and cell signaling. Magnesium deficiency is linked with increased risk of cardiovascular disease and metabolic disorders, including hypertension and type 2 diabetes. Current magnesium intakes among people living in the United States are below recommended levels of 400-420 milligrams per day for men and 310-320 milligrams per day for women.

The double-blinded, randomized intervention study involved 22 patients with chronic heart failure. Fifteen of the patients received 800 milligrams of supplemental magnesium oxide daily for three months, while the remainder took a placebo. The study investigators measured small and large arterial elasticity and compliance, hemodynamic parameters, exercise capacity, and quality of life at the beginning of the study and again at one week and three months after the intervention. Several of the patients dropped out of the study, with only five completing the full three-month intervention.

Patients who took the magnesium supplement had improved small arterial compliance, a measure of endothelial function. Reduced compliance is an indication of abnormalities in vascular structure.

This study suggests that supplemental magnesium improves endothelial function in symptomatic heart failure patients. However, this was a very small study group, so further study in a larger group of participants is warranted.

Link to full study.

Coenzyme Q10 may be beneficial in treating heart failure.

Coenzyme Q10 (CoQ10) is a fat-soluble nutrient that helps convert food into energy and protects cells against damage from reactive oxygen species. It is produced by the body and is particularly abundant in the heart, liver, kidneys, and pancreas. Findings from a 2014 studied demonstrated that CoQ10 is beneficial in treating heart failure.

People who have heart failure often have low levels of CoQ10 in their heart tissue. Low levels correlate with the severity of symptoms and the extent of left ventricular dysfunction – the inability of the ventricle to fill appropriately. Low plasma CoQ10 levels are independent predictors of death among people with heart failure.

The study, called Q-SYMBIO, was a prospective, randomized, double-blind, placebo-controlled trial involving 420 heart failure patients at 17 European, Asian, and Australian medical centers. Roughly half of the participants took 100 milligrams of CoQ10 three times daily for two years, while the remainder took a placebo. The authors of the study monitored the patients for changes in their New York Heart Association (NYHA) functional classification, capacity to perform a six-minute walk test, and levels of N-terminal pro–B type natriuretic peptide (NT-proBNP) after 16 weeks of the intervention. NT-proBNP is a pro-hormone that increases as heart failure worsens and decreases when the condition is stable. The authors also tracked whether the participants experienced a major cardiovascular event during the two-year period.

No changes in the participants’ NYHA classification, walk test, or NT-proBNP were noted after 16 weeks of the intervention. However, after two years, 26 percent of the participants in the placebo group experienced a major cardiovascular event, whereas only 15 percent of the patients in the CoQ10 group did. Those who took CoQ10 were less likely to die from cardiovascular-related causes or other causes of premature death and were less likely to require hospitalization. Those who took CoQ10 also saw marked improvements in their NYHA classification after two years.

These findings suggest that CoQ10 is beneficial in the treatment of heart failure and may reduce the risk of cardiovascular-related or other causes of premature death.

Link to full study.

NAD+ may be beneficial in treating a common form of heart failure.

Nicotinamide adenine dinucleotide (NAD+) plays an essential role in multiple physiological processes, including energy metabolism, DNA repair, and immune activation. Cellular NAD+ production declines with age, however, and its depletion has been implicated in the onset and progression of a wide range of age-related conditions, including cardiovascular disease. Findings from a new study suggest that NAD+ is beneficial in treating heart failure with preserved ejection fraction.

The heart’s ejection fraction is a measure of how much blood the left ventricle pumps with each contraction. Heart failure with preserved ejection fraction, a condition in which the heart muscle contracts normally but the ventricles don’t properly relax, is a leading cause of hospitalization in older adults. Few therapies for the condition exist, but caloric restriction has been shown to improve disease status in people with heart failure with preserved ejection fraction. Increasing cellular levels of NAD+ mimics the effects of caloric restriction.

The study involved both rodents and humans. In the rodent portion of the study, the authors gave nicotinamide, a precursor to NAD+, to mice and rats that had cardiovascular dysfunction related to aging, salt-sensitivity, or obesity. The animals’ heart function improved in each of the scenarios via enhanced diastolic function, improved heart bioenergetics, and reduced comorbidities, including reductions in blood pressure and body fat.

The human study drew on nutrition and death rate data from a prospective, population-based survey of atherosclerosis among 40- to 79-year-old men and women. The data indicated that higher dietary intake of NAD+ precursors reduced the risk of all causes of premature death, especially those related to cardiovascular diseases. People who consumed more NAD+ precursors were also less likely to have high blood pressure. These findings held true even after taking into account participants’ age, sex, smoking, diabetes, alcohol intake, body mass index, and total cholesterol.

These findings demonstrate that NAD+ precursors show promise as a means of treating heart failure with preserved ejection fraction. The FMF team has developed a collection of articles related to NAD+ and its precursors, nicotinamide mononucleotide and nicotinamide riboside so you can learn more about these important compounds.

Link to study abstract.

Curcumin maintains muscle power and reduces muscle soreness after plyometric exercise.

Plyometric exercises involve quick, powerful movements to promote speed, endurance, and strength. Loss of muscle power and delayed onset muscle soreness commonly occur after plyometric exercise. Findings from a new study suggest that curcumin maintains muscle power and reduces muscle soreness after plyometric exercise.

Curcumin in a bioactive compound produced by the plant Curcuma longa, a member of the ginger family. Curcumin exerts a wide array of beneficial health effects, including anti-inflammatory, anti-cancer, and anti-diabetes properties. It is responsible for the bright yellow pigment of turmeric, a type of spice commonly used in Indian food.

The study involved 22 healthy men and women who took either 500 milligrams of curcumin or a placebo twice daily for 10 days surrounding a single session of plyometric exercise (six days before, the day of, and three days afterward). The exercise consisted of five sets of 20 drop jumps performed from a 24-inch-high platform with a 60-second period of rest between sets. The investigators measured creatine kinase (a marker of muscle damage) and erythrocyte sedimentation rate (a marker of inflammation) in the participants’ blood. The participants performed a vertical jump and provided subjective assessments to gauge muscle soreness pre-supplementation, 24-hours and immediately pre-exercise, immediately afterward, and 24, 48 and 72 hours post-exercise.

Both groups had elevated creatine kinase and soreness immediately after performing the exercise. Those who took curcumin reported less soreness 48 and 72 hours after the exercise, even though there was no difference in creatine kinase levels between the two groups. The participants’ erythrocyte sedimentation rate was elevated immediately after the exercise, but the levels were within normal limits with little difference between the two groups. Those who took curcumin performed better on the vertical jump over time, but the placebo group saw decrements in the performance of this test.

These findings suggest that curcumin reduces soreness and helps maintain muscular power following plyometric exercise.

Link to study abstract.

Caffeine consumption during pregnancy alters neurodevelopment in the fetal brain.

Caffeine is a bioactive compound widely consumed in beverages, foods, and dietary supplements. Current guidelines recommend that women limit caffeine during pregnancy to 200 milligrams (roughly the amount in a 12-ounce serving) per day. Findings from a new study suggest that caffeine consumption during pregnancy alters neurodevelopment in the fetal brain.

During pregnancy, caffeine crosses the placenta and passes into the fetus and amniotic fluid. Maternal caffeine metabolism decreases during pregnancy, extending the half-life of the compound in the mother’s bloodstream to as much as 18 hours by the end of pregnancy. The placenta and fetus lack the necessary enzymes to metabolize caffeine, so fetal exposure is proportional to maternal intake.

The authors of the study analyzed structural MRI data from more than 9,100 children between the ages of nine and 10 years old who were enrolled in the Adolescent Brain Cognitive Development (ABCD) Study. Of particular interest to the researchers were the brain’s white matter tracts – the organized bundles of axons that connect one part of the brain to another. They assessed the effects of caffeine exposure on cognitive measures (working memory, task efficiency) and psychopathology measures (externalization, internalization, somatization, and neurodevelopment).

They found that roughly half of the children were exposed to caffeine during their mothers’ pregnancies. Those who were exposed to caffeine exhibited alterations in the microstructure of the inferior fronto-occipital fasciculus (tracts associated with language processing and goal-oriented behavior) and the corticospinal tract of the left hemisphere (tracts associated with motor activity). The children who were exposed to caffeine also exhibited worse outcomes in terms of psychopathology, but their cognitive function was unaffected.

These findings suggest that caffeine exposure during pregnancy leads to neurodevelopmental problems due to microstructural alterations in the brain.

Link to study abstract.

Eating fish rich in omega-3 fatty acids reduces risk of asthma in some children.

Asthma is a respiratory condition characterized by narrowed airways and difficulty breathing. It commonly manifests in early childhood and affects more than 339 million people worldwide. Findings from a new study suggest that dietary intake of omega-3 fatty acids among children who carry a common variant in the fatty acid desaturase gene reduces the risk of developing asthma.

Fatty acid desaturase is an enzyme that drives the biosynthesis of mono- and polyunsaturated fatty acids in the body. Impairments in the expression and activity of fatty acid desaturases drives many pathological conditions.

The authors of the study analyzed data from healthy male and female children enrolled in the Avon Longitudinal Study of Parents and Children, a prospective birth cohort study conducted in England. They assessed dietary intake of omega-3 fatty acids from fish via food frequency questionnaires when the children were 7 years old and collected information about the incidence of asthma among the children when they were 11 and 14 years old. They duplicated their analysis in the Swedish BAMSE birth cohort.

The authors of the study found no links between intake of omega-3 fatty acids from fish and the incidence of asthma in the full group of children. But when they looked at the subset of children who carried a variant in the fatty acid desaturase gene, they found that high intake of omega-3 fatty acids from fish reduced the risk of developing asthma 51 percent. These findings were replicated in the BAMSE cohort.

These findings suggest that dietary intake of fish rich in omega-3 fatty acids during childhood reduces the risk of developing asthma among children who carry a genetic variant of an enzyme involved in fatty acid synthesis. The authors of the study cautioned that their study was observational and did not identify any causes to explain the relationship.

Link to study abstract.

Restoring immune cell metabolism reduces inflammation and slows cognitive decline in mice.

Aging involves the collective physiological, functional, and mental changes that accrue in a biological organism over time. A key driver of aging is inflammation, which affects multiple organs, including the brain. Findings from a new study demonstrate that altering prostaglandin E2 signaling in macrophages reduces inflammation and slows cognitive decline in mice.

Prostaglandin E2 is an important mediator of inflammation, angiogenesis, cell survival, and proliferation. It is produced via the enzymatic conversion of arachidonic acid, a type of fatty acid. Binding of prostaglandin E2 to its receptors on immune cells alters glucose metabolism in the cells and drives inflammation. Prostaglandin E2 levels increase with age and in the setting of neurodegenerative disease.

Macrophages are a type of immune cell. They are key players in the initiation, maintenance, and resolution of inflammation.

The investigators first studied peripheral blood mononuclear cells collected from younger (less than 35 years) and older (greater than 65 years) human donors to better understand how prostaglandin E2 signaling affected macrophage energy production. They found that prostaglandin E2 reduced glycolysis (the breakdown of glucose) and impaired mitochondrial oxygen use. The primary receptor that mediated these effects was the EP2 receptor, which was present in higher quantities in the macrophages of older donors. Then they treated the cells with an inhibitor to block the EP2 receptor and found that the alterations in energy production reversed.

Next, the investigators studied mice that are predisposed to have Alzheimer’s disease. They treated the animals with EP2 receptor inhibitors or deactivated their EP2 gene. They found that in both situations the macrophages had better energy production, and the mice had lower levels of inflammation and cognitive decline.

These findings suggest that inhibition of immune-related processes that promote inflammation restores immune cell energy production and slows cognitive decline in mice. Learn more about the role of inflammation in cognitive decline in this episode featuring Dr. Dale Bredesen.

Link to study abstract.

Fecal microbiota transplant improves immunotherapy response among melanoma patients.

Fecal microbiota transplant is a therapeutic strategy that involves transfer of feces from a donor to a recipient. The goal of fecal transplant is to restore the microbial balance in the gut of the recipient as a means to improve health. A new study demonstrates that fecal microbiota transplant improves the response to immunotherapy among melanoma patients.

Immunotherapy exploits the immune system to treat cancer. One type of immunotherapy, anti-programmed cell death protein 1 (PD-1) therapy is beneficial in treating patients with advanced melanoma. However, gut microbial composition influences anti-PD-1 efficacy in preclinical models and cancer patients. About 40 percent of melanoma cancer patients do not respond to immunotherapy.

The authors of the study administered fecal microbiota transplants and anti-PD-1 immunotherapy (a drug called pembrolizumab) to melanoma patients who had not responded to all other therapies, including anti-PD-1. The fecal microbiota donors were people who previously demonstrated robust responses to anti-PD-1 immunotherapy.

More than one-third of the patients who received the transplants responded favorably to the anti-PD-1 immunotherapy despite having not responded before the transplant. The types of gut microbes associated with response to anti-PD-1 increased, as did activation of CD8+ T cells. The number of interleukin-8–expressing myeloid cells (which are involved in immunosuppression) decreased.

These findings suggest that fecal microbial transplant is a viable option for improving the response to immunotherapy among melanoma patients and underscore the need for greater understanding of the role the gut microbiota play in immune function.

Link to study abstract.

Vitamin D is a cost-effective means to reduce the number of cancer deaths.

Cancer is the second leading cause of death worldwide, claiming the lives of nearly 10 million people each year. As the number of cancer drugs has increased in recent years, so too have the costs associated with their use. Findings in a recent report indicate that vitamin D may reduce the number of cancer deaths, saving thousands of dollars.

The authors of the study drew on data regarding age- and sex-specific cancer deaths in the German Center for Cancer Registry. They estimated the costs of cancer treatment and years of living lost in people over the age of 50 years since most cancer deaths occur in this age group and because most vitamin D trials are conducted in older adults. They also estimated the costs of vitamin D supplementation and summarized the findings from three recent meta-analyses investigating the effects of vitamin D supplementation on cancer deaths.

The authors estimated that the end-of-life cancer costs in Germany were more than $48,000 per patient, but the cost of vitamin D supplementation was only $30 per year. They estimated that 1,000 IU of vitamin D daily would reduce cancer deaths in Germany by 13 percent, or about 30,000 lives, at a savings of more than $308 million.

These findings suggest that vitamin D is a cost-effective means to reduce cancer deaths, especially among older adults. Learn how vitamin D slows epigenetic aging – a driver of cancer – in this episode featuring Dr. Steve Horvath.

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