Science Digest – March 26, 2021

Dear Premium Members,

We’re excited to bring you another issue of our Science Digest, full of amazing news stories curated just for you, our members. Read on to learn how…

Sulforaphane inhibits NLRP3 inflammasome activation in mice microglia cells.
Omega-3 fatty acids may reduce muscle loss in older adults.
Exercise reverses effects of sleep deprivation on cardiovascular health.

And much more!

Don’t forget: We’ve got another Crowdcast live Q&A coming up Saturday, April 10th, at 9:30 am PDT. [Note: This is a week later than usual.] The code for this event is mitochondria. Remember, you can always access the most recent event code and Q&A calendar by visiting your dashboard at


Rhonda and team
Science Digest – March 26, 2021
Sulforaphane inhibits activation of the NLRP3 inflammasome in mice microglia cells.

Sulforaphane is a bioactive compound derived from certain cruciferous vegetables, such as broccoli and broccoli sprouts. It exerts potent anti-inflammatory properties and switches on the activity of a vast array of cellular protective proteins. A new study in mice demonstrates that sulforaphane inhibits activation of the NLRP3 inflammasome in mice microglia cells via inhibition of the NF-kB pathway and altered gene expression.

Inflammasomes are large, intracellular complexes that detect and respond to internal and external threats. Activation of inflammasomes has been implicated in a host of inflammatory disorders. The NLRP3 inflammasome in particular triggers the release of proinflammatory cytokines interleukin-1 beta (IL-1β) and IL-18 and drives pyroptosis, a form of cell death that is triggered by proinflammatory signals and closely linked with inflammation.

Microglia are the brain’s resident immune cells. They serve an essential role in maintaining brain microenvironment homeostasis. Acute activation of microglia modulates inflammation and neurotoxicity, but chronic activation promotes brain inflammation and damage.

NF-kB is a family of proteins present in mammalian cells. NF-kB influences several aspects of the body’s stress response via its participation in signaling pathways that drive pro-inflammatory processes, ultimately regulating DNA transcription, cytokine production, cell survival, and immune function.

The authors of the study triggered the activity of the NLRP3 inflammasome in mice microglia cells that had been treated with or without sulforaphane. Then they assessed the level of pyroptosis in the cells, measured expression of IL-1β and IL-18, and tracked the activity of NF-kB. They also measured the cells’ mitochondrial production of reactive oxygen species and mitochondrial membrane integrity.

The cells treated with sulforaphane showed less pyroptosis, reduced expression of IL-1β and IL-18, and impaired NF-kB activity than the untreated cells. Sulforaphane also reduced reactive oxygen species production and helped maintain mitochondrial membrane integrity. These findings suggest that sulforaphane protects the brain via inhibition of the NF-kB pathway and subsequent inhibition of the NLRP3 inflammasome.

Link to study abstract.

Omega-3 fatty acids may reduce muscle loss in older adults.

Sarcopenia is an age-related progressive condition characterized by the loss of skeletal muscle mass and strength. It is one of the leading causes of functional decline and loss of independence in older adults. Contributing factors for sarcopenia include poor nutrition, low physical activity, and inflammation, among others. Findings from a recent meta-analysis suggest that omega-3 fatty acids are beneficial in preventing or treating sarcopenia.

Omega-3 fatty acids participate in a wide range of physiological processes and are essential for human health. Some evidence demonstrates that omega-3 fatty acids play roles in muscle mass synthesis and function. Omega-3 fatty acids include alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). ALA is found mainly in plant oils such as flaxseed, soybean, and canola. DHA and EPA are found in fish and other seafood. The human body can convert some ALA into EPA and then to DHA, but the process is very inefficient.

The authors analyzed data from 10 randomized controlled intervention trials investigating the effects of increased omega-3 fatty acid intake on skeletal muscle mass, muscle strength, or muscle performance. More than 550 adults aged 60 years and older were included in the studies, the duration of which spanned 10 to 24 weeks. Outcomes included changes in muscle mass, muscle strength, or physical performance, assessed by walking time or the Timed Up & Go Test (TUG).

The trials provided omega-3 fatty acids from a variety of sources, including fish oil, flaxseed oil, and healthy dietary patterns that adhered to a low omega-6 to omega-3 ratio. Doses ranged from 0.16 to 2.6 gram per day of EPA and from zero to 1.8 grams per day of DHA. One study provided 14 grams per day of ALA. The participants saw increases in muscle mass of about 0.33 kilograms (~11 ounces), and their TUG test times decreased by 30 seconds. Participants who consumed more than 2 grams of omega-3s per day saw greater improvements, with increases in muscle mass of 0.67 kilograms (~1.8 pounds). For those enrolled in interventions lasting six months or longer, walking times improved by nearly 2 meters per second.

These findings suggest that nutritional interventions that include dietary and/or supplemental omega-3 fatty acids improve muscle mass and physical performance in older adults. The relatively small number of trials and the varying doses, duration, and study designs limit the application of the findings, however.

Link to full study.

Exercise reverses effects of sleep deprivation on cardiovascular health.

Just one night of sleep deprivation can impair arterial function, and chronically poor sleep increases the risk of developing cardiovascular disease. Conversely, high intensity interval exercise can improve multiple markers of cardiovascular health. In this report, researchers tested the effects of exercise on flow mediated dilation, a measure of vascular function, in sleep-deprived participants.

Flow mediated dilation measures how wide an artery expands (dilates) in response to increased blood flow. Meals high in fat normally cause dysfunction in blood vessels, impairing their ability to expand. Previous research reports that high intensity exercise improves flow mediated dilation following a meal.

Fifteen healthy active men (average age, 31 years) completed three nights of sleep for this study. The first night, participants slept a full eight hours and ate a high-fat test meal the next morning. The second night, participants slept a full eight hours, then performed high intensity interval training before eating. The third night, participants slept three and one half hours or less, then performed the same exercise and ate the same meal. The researchers measured the participants’ flow mediated dilation at multiple time points.

After comparing the post-meal flow mediated dilation following a full night of sleep and a full night of sleep plus exercise, the authors found that exercise improved arterial function. Impressively, the benefit of exercise remained following a night of sleep deprivation. Flow mediated dilation rates were similar between exercise conditions regardless of sleep duration the night before.

The authors concluded that high intensity exercise improves arterial function and that these benefits remain even after a night of sleep deprivation. However, they recommended that people get a full night of sleep before strenuous exercise to get the most benefit.

Link to full study.

Learn how exercise can promote good sleep in this clip featuring Dr. Matthew Walker.

Leaky gut decreases the beneficial effects of dietary polyphenol compounds in older adults.

Polyphenols are bioactive compounds found in plant-based foods, many of which have beneficial effects in the body. Bacteria in the human gut break down polyphenols into smaller compounds to increase their absorption. Authors of a recent study measured the relationship between gut health and the absorption of beneficial polyphenols in older adults.

As humans age, the quality of the population of microbes that comprise the gut microbiota decreases, leading to poor gut barrier integrity and causing contents of the gut to leak into the bloodstream, a condition commonly referred to as “leaky gut.” This leaking of toxins, viruses, and bacteria is associated with increased inflammation and disease risk. In addition to causing a leaky gut, poor microbiota quality may decrease the beneficial effects of polyphenol-rich plant foods.

The authors tested the effects of a polyphenol-rich diet in 51 adults (greater than 60 years of age) residing in an assisted living setting. Participants consumed either the normal menu prepared by their facility for eight weeks or a menu that included three servings of polyphenol-rich fruits, teas, and cocoa for eight weeks and then switched to the opposite diet. The researchers collected blood samples to measure serum zonulin, a marker of gut barrier integrity, and urine samples to analyze polyphenol metabolite content before and after each diet period.

Overall, serum zonulin decreased following eight weeks of a polyphenol-rich diet, indicating that gut barrier integrity improved. Participants who started the trial with better gut barrier integrity had greater increases in blood levels of polyphenol metabolites compared to participants with leakier guts. The metabolites found in the group with greater gut barrier integrity were microbial-derived, suggesting these participants had a more health-promoting gut microbiota.

Based on these results, the authors hypothesized that changes in the gut microbiota damage the gut barrier and cause a subsequent reduction in the absorption of dietary polyphenol compounds. They concluded that personalized diet plans could be effective for managing leaky gut in older adults.

Link to full report.
Learn how to make a polyphenol-rich smoothie in this video.

Decreased brain derived neurotrophic factor, physical activity, and brain volume are associated with greater memory impairment.

Brain derived neurotrophic factor (BDNF) is a growth factor associated with decreased risk of dementia and improved cognitive function in humans. While BDNF promotes brain cell growth and plasticity, its precursor form, called proBDNF, has the opposite effect, promoting cell death. The authors of a recent report investigated the relationship between blood levels of proBDNF and memory loss.

The effects of Alzheimer’s disease on the brain can be observed 10 to 15 years before the onset of dementia, presenting the opportunity for early detection. Even though BDNF is known to cross the blood-brain barrier, whether blood levels of BDNF are reflective of BDNF activity in the brain is unclear. Establishing blood biomarkers of dementia risk provides a means for early intervention.

The authors recruited 256 older adults (average age, 68 years) without dementia living in a rural village in Japan. They analyzed magnetic resonance imaging (MRI) scans of the participants’ brains and measured blood levels of BDNF and proBDNF. Participants completed questionnaires to measure memory performance and physical activity habits.

The investigators reported that increased age and decreased physical activity were associated with poorer memory performance. MRI findings showed decreased volume in the hippocampus, the region of the brain associated with memory, in those with worse memory scores. Decreased blood levels of BDNF, but not proBDNF, were associated with worse memory performance.

These results echo earlier findings that exercise is associated with greater BDNF activity and better memory performance. The authors concluded that measuring blood levels of BDNF may be an effective strategy for early detection of dementia.

Link to full report.

Learn more about BDNF and brain health in our overview article.

Body fat increases the risk of death, while muscle mass decreases it.

Body mass index (BMI) is a measure of body size that is calculated by dividing a person’s weight by their height. An abundance of research has demonstrated that having a body mass index outside the normal range (18.5 to 25) increases the risk of death. However, body mass index does not accurately reflect body composition. Authors of a new report investigated the effects of body composition on risk of death.

Body composition is measure of how much of a person’s body weight comes from fat mass versus fat-free (muscle) mass. Having excess body fat is associated with an increased risk of developing a number of chronic diseases, while having larger quantities of fat-free mass is associated with increased disease risk. Previous research has demonstrated mixed results for the effect of body composition and risk of death, likely due to differences in study design.

The authors combined data from seven studies involving more than 16,000 participants between the ages of 20 and 93 years. Researchers measured body composition using bioelectrical impedance and adjusted for age and sex. They also interviewed participants about their health, lifestyle, and socioeconomic factors and tracked them for an average of 14 years.

After adjusting for a number of demographic and lifestyle factors, the researchers found that having body fat levels below or above the normal range increased risk of death among the participants. Those with high body fat (roughly 37 kilograms) were 56 percent more likely to die, while those with the highest fat-free mass were 30 percent less likely to die.

The authors concluded that fat mass and fat-free mass have opposite effects on the risk of death. They noted that their study included a large number of participants and a long follow-up period, which strengthened the quality of their results.

Link to full report.

Vitamin D supplementation and sunlight improve athletic performance.

Vitamin D regulates over 900 genes in the body that affect the immune, musculoskeletal, and endocrine systems, among others. Previous research has shown that vitamin D deficiency may decrease athletic performance. A study published in early 2020 in soccer players demonstrates the importance of maintaining year-round adequate vitamin D levels for athletes.

Estimates suggest that 60 percent of outdoor and 64 percent of indoor athletes may have insufficient vitamin D levels (defined as less than 30 ng/ml), which may impair aerobic capacity and muscle recovery. High-dose supplementation of 5,000 IU per day has been associated with increased vertical jump height and decreased sprint times.

Twenty-eight professional soccer players completed the study, which took place in three stages from January to September. In January, all players completed 10 days of sun exposure while training in Cyprus (latitude of 34 degrees north, 33 degrees east). Next, half of the players consumed 6,000 IU of vitamin D per day for six weeks and half consumed a placebo. In September (the end of the season) the researchers measured changes in serum vitamin D, serum testosterone, body composition, sprint times, and leg power compared to assessments completed in January.

The authors reported that both sun exposure and supplementation increased serum vitamin D levels, serum testosterone levels, and muscle mass, and decreased 5-meter sprint times. However, they noted that most players did not achieve high levels of vitamin D (greater than 50 ng/ml) by September, which may have affected their results.

The authors concluded that vitamin D insufficiency is a problem among athletes, even following summer sun exposure at southern latitudes. They recommended year-round supplementation to support optimal vitamin D status and maximize athletic performance.

Link to full report.

Omega-3 fatty acid supplementation improves cognitive function in adults without dementia.

Diets rich in omega-3 fatty acids have been shown to decrease the risk of Alzheimer’s disease. A growing number of studies have also demonstrated the benefits of omega-3 supplementation in adults with dementia. Authors of a recent report investigated the effects of omega-3 supplementation in adults without cognitive decline.

Both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the two main forms of omega-3 fatty acids, suppress inflammation, regulate neurogenesis, decrease oxidative stress, and protect the aging brain. Previous research has demonstrated that omega-3 fatty acids preserve white and gray matter volume in the brain.

Older adults (average age, 63 years) with stable coronary artery disease who were taking statin medication participated in this trial. Researchers assigned half of the participants to consume 1.9 grams of EPA and 1.5 grams of DHA per day for 30 months while the other half took no supplement. Participants completed a battery of five neuropsychological tests at baseline, 12 months, and 30 months.

Participants in the EPA + DHA group performed better in multiple cognitive domains including verbal fluency, language, memory, psychomotor speed and attention, and visual-motor coordination, compared to the group that took no supplement. This benefit was seen after 12 months of supplementation and remained significant after 30 months.

The authors noted that the high dose and length of supplementation were strengths of their study. They concluded that omega-3s should be recommended for cognitively healthy adults to prevent or delay cognitive decline.

Link to full report.

Micronutrient supplementation before pregnancy improves children’s long-term intellectual functioning.

Pregnancy and early childhood are periods of human development when the body has an increased requirement for micronutrients (vitamins and minerals). Animal studies have shown the importance of preconception nutrition for offspring development; however, long-term human trials are lacking. Investigators aimed to determine the long-term effects of preconception micronutrient supplementation on children’s intellectual functioning.

Several micronutrients play critical roles in fetal development. For example, folic acid supplementation during pregnancy prevents neural tube defects, and iron plays an important role in brain maturation, promoting cell division, myelination, and synaptic development. Less is known about the importance of other micronutrients, however.

The researchers assigned over 5,000 female participants to take folic acid (2,800 micrograms) only; iron plus folic acid (60 milligrams iron and 2800 micrograms folic acid); or multiple micronutrients (15 micronutrients including iron and folic acid) for an average of 33 weeks between baseline and conception. Researchers tracked 1,300 of the participants’ children from birth to the age of six years. They tested the children on multiple domains of intelligence and collected information regarding maternal health and home life.

Compared to children whose mothers received only folic acid, children in the iron plus folic acid and mixed micronutrient group performed better in multiple domains, including verbal comprehension, perceptual reasoning, working memory, and processing speed. This effect was strongest for children whose mothers consumed the supplements for greater than 26 weeks before conception. The effects of supplementation were also stronger for children born to households with low socioeconomic status.

The authors concluded that preconception micronutrient supplementation is important to optimize child development and recommended the promotion of supplementation to all females of child-bearing age.

Link to full report.

Prolonged fasting activates multiple metabolic pathways.

Fasting – the voluntary abstinence from food and drink – triggers the activation of a vast array of biochemical processes and signaling pathways that optimize human performance and physiological function, possibly slowing the processes of aging and disease. A recent study found that prolonged fasting induced profound, diverse increases in the metabolites present in blood.

Metabolites are substances produced in an organism, cell, biological fluid, or tissue during metabolism. The collection of these metabolites in their entirety is referred to as the metabolome. Metabolomics is an emerging field of study involving the identification and quantification of the metabolome at a specific time point to create a metabolic profile that provides information about the body’s physiological state. Previous research has identified 126 distinct metabolites in human blood.

The authors of the study drew blood samples from four healthy, young (average age, 29 years) non-obese volunteers at three intervals (10, 34, and 58 hours) during a period of fasting. They analyzed the participants’ metabolomic profiles in whole blood, plasma, and red blood cells and identified increases or decreases in the metabolites.

Their analysis revealed that the participants’ blood glucose levels remained within the normal range (70 to 80 mg/dL) and ATP levels were consistent throughout the fasting period. Levels of most of the previously identified metabolites remained unchanged during the fast, but 44 metabolites increased, and two decreased.

Metabolites that increased included butyrate, branched-chain amino acids, carnitines, organic acids, coenzymes, pyrimidines, purines, antioxidants, and molecules associated with the pentose phosphate pathway. These compounds support multiple metabolic pathways and biological processes, including gluconeogenesis (the production of glucose from ketones, glycerol, and amino acids), protein synthesis, and mitochondrial activity, among others. The compounds that decreased were aspartate (an amino acid) and gluconate (a glucose derivative).

These findings suggest that fasting induces a metabolically active state in healthy, young adults. However, this was a very small study, so larger studies are needed to confirm the findings.

Link to full study.

Learn more about fasting in this Q&A featuring Dr. Rhonda Patrick.

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