Fwd: Science Digest – July 16, 2021

Hey, Premium Members!

We have another awesome issue of the Science Digest for your weekend pleasure. Read on to learn how…

Eating protein at breakfast is best for growing muscle mass.
Eating milk chocolate in the morning (but not at night) boosts metabolism.
Omega-3 fatty acids reduce migraine headaches.

And much more!

In case you missed it: We released a brand-new interview, featuring FMF friend Dr. Satchin Panda in June. He and I talked about circadian rhythms, time-restricted eating, and optimizing performance. You can find the Google Presentation from that session here.

In other news: We’ve got another Crowdcast live Q&A coming up August 7th at 9:30am PDT. The code for this event is HIIT. Register here. You can catch the replay from the session that happened earlier this month which covered ivermectin, COVID-19 vaccines, and more, by clicking here.


Rhonda and team

Science Digest – July 16, 2021
Eating protein at breakfast is best for growing muscle mass.

Dietary protein is essential for the growth of skeletal muscle, a process called hypertrophy. Circadian rhythms – the body’s 24-hour cycles of biological, hormonal, and behavioral patterns – modulate a wide array of nutritional and metabolic processes, including amino acid absorption and utilization. However, it is unclear how circadian rhythms affect muscle hypertrophy. A report published this month suggests that distributing dietary protein equally across meals is best for maintaining muscle mass.

Circadian clocks located in the brain and other organs are driven by changes in the expression of genes such as Circadian locomotor output cycles kaput, commonly referred to as “Clock.” Mice that do not express the Clock gene do not experience day-night variations in metabolism, disrupting amino acid absorption by skeletal muscle. Amino acids are required for activation of genes such as the mammalian target of rapamycin (mTOR), which promotes autophagy, a system of disassembly and recycling of unnecessary or dysfunctional cellular components that is essential for hypertrophy.

The investigators conducted a set of experiments in mice and an observational study in humans. They fed mice two meals per day containing either 11.5 percent or 8.5 percent protein for two weeks. Mice consumed these meals in three patterns of protein distribution: high protein at breakfast and low protein at dinner; equal protein at both meals; or low protein at breakfast and high protein at dinner. In a second experiment, the researchers fed mice branched chain amino acids, which are used in high concentrations by the body for building muscle, at breakfast or dinner. In both experiments, the researchers performed muscle overloading, which puts stress on muscles to encourage hypertrophy, similar to weight lifting in humans. They measured changes in muscle strength, muscle gene expression, plasma amino acid concentrations, plasma growth factor concentrations, and autophagy.

All mice gained muscle mass in response to muscle overload; however, mice that consumed a high-protein breakfast and low-protein dinner had greater gains in muscle mass and rate of hypertrophy than mice that consumed a low-protein breakfast and high-protein dinner. Likewise, mice that consumed a branched chain amino acid supplement in the morning gained more muscle mass and had a higher rate of hypertrophy than mice that consumed the supplement at night. Mice that do not express the Clock gene did not experience gains in muscle mass or hypertrophy with early protein or branched chain amino acid intake, suggesting these gains were circadian-related.

The researchers found that branched chain amino acid concentrations increased following a high-protein meal regardless of time, so these gains in hypertrophy were not due to circadian fluctuations in plasma amino acid concentrations. Likewise, insulin-like growth factor concentrations increased following a high-protein meal regardless of time and likely did not affect the rate of hypertrophy. However, the activation of autophagy in overloaded muscle was greater in mice that consumed a high-protein breakfast compared to a high-protein dinner, potentially contributing to a higher rate of hypertrophy.

Next, researchers recruited 60 women who completed a questionnaire about their consumption of protein foods at breakfast, lunch, and dinner. The researchers classified participants as early protein consumers or late protein consumers based on their answers and measured the participants’ body composition, physical activity, and grip strength.

Muscle mass tended to be higher in participants who consumed protein earlier in the day, but this relationship was not statistically significant. Early protein consumers also had significantly greater grip strength and higher skeletal muscle index, which is the ratio of muscle mass in a person’s arms and legs to their height. These relationships remained significant even after taking diet and activity into account. Finally, skeletal muscle index increased as the percent of daily protein eaten at breakfast increased, meaning the more protein that was consumed in the morning, the greater the increase in skeletal muscle index.

These results indicate that circadian genes drive day-night variation in muscle metabolism and protein utilization. Early protein consumption is more beneficial for growing and maintaining muscle than late protein consumption.

Link to full report.
Learn more about circadian rhythms from the author of this paper, Dr. Satchin Panda, in this latest episode featuring Dr. Rhonda Patrick.

Milk chocolate exerts differential health effects, depending on the timing of consumption.

A wide range of beneficial health effects have been ascribed to consumption of chocolate, especially dark chocolate, which is rich in bioactive compounds that exert antioxidant, anti-inflammatory, and cardioprotective properties. Consumption of milk chocolate, however, is widely associated with harmful effects (such as weight gain) due to its high caloric content. Findings from a recent study suggest that milk chocolate exerts differential health effects, depending on the timing of consumption.

A growing body of evidence suggests that the timing of food intake plays important roles in metabolic regulation and circadian rhythmicity. For example, eating a large, carbohydrate-rich meal late in the evening impairs glucose tolerance and insulin secretion, contributing to the risk of developing type 2 diabetes.

The study involved 19 Caucasian postmenopausal females with normal weight or overweight (average age, 52 years; average body mass index, 25). The participants followed their typical dietary pattern for the duration of the study, with three interventions in random order: 100 grams of milk chocolate (roughly the amount in a standard size candy bar – 542 calories) with breakfast for two weeks, within an hour of waking up; 100 grams of milk chocolate for two weeks, within an hour before bedtime; and no chocolate for two weeks. A one-week washout period separated each intervention. They completed questionnaires that assessed their hunger and appetite for sweets at various timepoints throughout the study. The study investigators assessed the participants’ anthropometric measures, including body mass index, total body fat, and waist circumference. They also assessed the composition and function of the participants’ gut microbiota and measured their blood glucose levels, body temperature, and sleep quality.

The study investigators found that consuming 100 grams of milk chocolate in the morning or evening did not cause the women to gain weight. The women reported that they felt less hunger and less desire to eat sweets. When they ate milk chocolate in the morning, they consumed about 300 fewer calories during the rest of the day; their fat burning increased; their fasting blood glucose and waist circumference decreased; and their sleep quality was impaired. When they ate milk chocolate in the evening, they consumed about 150 fewer calories during the rest of the day; their physical activity, heat dissipation after meals, and carbohydrate metabolism increased; and their sleep quality improved. Both timings of chocolate consumption altered the composition and function of the gut microbiota.

These findings demonstrate that the timing of milk chocolate consumption has varied effects on metabolism, dietary intake, and sleep function, potentially influencing overall health. Learn how food timing influences cancer risk in this clip featuring Dr. Ruth Patterson.

Link to full report.

Omega 3 fatty acids may reduce migraine headaches.

Migraine is a neurological disorder commonly manifested as severe headache pain accompanied by nausea, vomiting, and light sensitivity. Approximately 15 percent of people worldwide experience migraine, with women reporting migraine more often than men. Findings from a new study suggest that oxylipins reduce headache pain among people with migraine.

Oxylipins are byproducts of polyunsaturated fatty acid metabolism. They play both pro- and anti-inflammatory roles in the human body and are key regulators of pain. Whereas oxylipins derived from omega-6 fatty acids promote pain, those derived from omega-3 fatty acids reduce pain.

The authors of the report conducted a three arm, parallel group, randomized controlled trial. Participants included 182 adults (average age, 38 years) who experienced migraine headaches five to 20 times per month. They were randomly assigned to consume one of three specially designed diets that contained omega-3 fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) and an omega-6 fatty acid (linoleic acid) for 16 weeks. A high omega-3 diet provided 1.5 grams of EPA+DHA and approximately 7 percent of total caloric intake from linoleic acid daily. A high omega-3/low omega-6 diet provided 1.5 grams of EPA+DHA and approximately 1.8 percent or less of total calories from linoleic acid. A control diet provided less than 150 milligrams of EPA+DHA and approximately 7 percent of total caloric intake from linoleic acid daily. Participants tracked their migraine headache frequency, and the authors measured levels of 17-hydroxydocosahexaenoic acid (17-HDHA), a type of pain-reducing oxylipin, in the participants’ blood.

The high omega-3 and high omega-3/low omega-6 diets decreased the number of headache hours participants experienced per day as well as the number of headache days experienced per month. The high omega-3/low omega-6 diet was nearly twice as effective at reducing the number of headache days per month than the high omega-3 diet, suggesting that lowering linoleic acid provided an additional beneficial effect. The high omega-3 and high omega-3/low omega-6 diets both increased 17-HDHA levels in the participants’ blood, but the control diet did not.

These findings demonstrate that omega-3 fatty acids may help reduce migraine headaches and highlight yet another beneficial health effect associated with these healthful fats.

Link to full report.

Blueberry anthocyanins improve cardiovascular health.

Aging induces a number of disease-related changes to the cardiovascular system, including dysfunction of the endothelial cells that line blood vessels. Eating fruits and vegetables, which are rich in a variety of beneficial bioactive compounds, may slow cardiovascular aging. Investigators tested the effects of anthocyanin compounds from blueberries on flow-mediated dilation.

Flow-mediated dilation refers to the capacity of an artery to expand in response to increased blood flow. It is a widely accepted measure of vascular endothelial function, and poor flow-mediated dilation is a recognized feature of cardiovascular disease. Previous research has demonstrated a relationship between higher blueberry and strawberry intake and decreased risk of heart attack. Blueberries contain a number of bioactive compounds, including anthocyanins, procyanidins, flavonols, phenolic acids, and other phenolic compounds. The body subjects these compounds to a wide range of chemical processes, yielding bioactive metabolites. How these bioactive compounds differ in their effects on cardiovascular health is unclear.

The authors analyzed data from four studies involving a total of 60 participants and conducted a follow-up experiment in mice. In the first study, participants received one of five treatments on five separate days: a control beverage that mimicked blueberry juice; the control beverage with fiber added; the control beverage with added minerals and vitamins; pure anthocyanins; and a beverage made with freeze-dried blueberries. The investigators measured flow-mediated dilation at baseline and one, two, and six hours after participants ingested the beverages. In the second study, participants consumed capsules containing one of six concentrations of anthocyanins (0, 80, 160, 240, 320, or 480 milligrams) on six separate days. The investigators measured flow-mediated dilation at baseline and two and six hours after ingestion.

The third study measured the effects of long-term blueberry consumption. Participants consumed 11 grams of wild blueberry powder (equivalent to about four ounces of fresh blueberries) dissolved in water twice daily for 28 days. The investigators measured flow-mediated dilation at baseline and at seven, 14, 21, and 28 days of consumption. In the fourth study, participants consumed a drink containing 11 grams of wild blueberry powder or a control beverage twice daily for at least 28 days. The investigators measured flow-mediated dilation at baseline and two hours after ingestion on the first day of the intervention and after at least 28 days of consumption. For the follow-up experiment, investigators gave mice an injection of bioactive metabolites that they had identified from the previous human experiments and measured the effects on flow-mediated dilation.

Isolated anthocyanins improved endothelial function as measured by flow-mediated dilation in a dose-dependent manner, meaning that the effects were more robust as dose increased. The effects of these isolated anthocyanins were similar to those of wild blueberries. However, control beverages containing fiber, minerals, or vitamins and minerals had no significant effect on flow-mediated dilation. Twice daily wild blueberry consumption for one month also increased long-term flow-mediated dilation. Finally, injection of metabolites derived from the phenolic compounds found in blueberries improved flow-mediated dilation in mice.

These results demonstrate the beneficial effects of blueberries on cardiovascular health and elucidates the function of anthocyanin compounds as major mediators of vascular function in mice and humans.

Link to full report.

Greater muscle strength reduces depression risk.

Depression is characterized by mood alterations, such as increased sadness and irritability, and physiological changes, such as decreased sleep, appetite, and sexual desire. Previous research has reported a relationship between increased muscle strength and lower depression risk in older adults. Findings of a recent study detail the relationship between muscle strength and depression risk in young adults.

Cytokines are proteins that participate in cell-signaling. Pro-inflammatory cytokines are increased in depression and contribute to the dysfunction of neurotransmission, hippocampal neurogenesis, and stress-related nervous system activation. Skeletal muscle cells secrete a number of pro-inflammatory cytokines, such as interleukin (IL)-6, IL-8, and IL-15. A previous study demonstrated a relationship between lower levels of inflammation in adolescents with increased muscle strength and decreased body fat, but the study did not measure depression risk.

The authors included 600 female participants without depression (average age, 19 years) in their analysis who were part of a larger observational study of physical fitness and health in Chinese college students. Participants completed a survey to measure depression symptoms and a physical exam including the use of a dynamometer to measure grip strength, a proxy for total skeletal muscle strength. The authors collected these measures at baseline and at a one-year follow-up. They classified participants into one of four categories based on the amount of grip strength they gained over the one-year study period.

At the one-year time point, about 11 percent of participants reported depressive symptoms. Participants who gained the most grip strength over the one-year study period had a 66 percent lower risk of depression compared to participants who gained the least grip strength. Participants with the greatest gains in grip strength tended to be younger and smoke less at baseline than participants with the least gains in grip strength. Finally, gains in grip strength were significantly related to body mass index (BMI) at baseline.

Underweight, defined as a BMI less than 18.5, was more common in participants with the lowest gains in grip strength (43 percent), while overweight, defined as a BMI greater than 25, was more common in participants with the greatest gains in grip strength (23 percent).

The authors concluded that increased grip strength is associated with a lower risk of depressive symptoms in young adults.

Link to full report.
Learn more about how exercise may be beneficial in treating or managing symptoms of depression in this episode featuring Dr. Rhonda Patrick.

Fermented foods decrease inflammation and increase diversity of the gut microbiota.

The gut microbiota is composed of the community of bacteria, archaea, fungi, and viruses that live in the human intestine. Dietary components influence the composition and activity of the microbiota. For example, foods high in dietary fiber, such as whole grains and beans, and fermented foods, such as yogurt and sauerkraut, support an abundant and diverse gut microbiota, which is associated with lower disease risk. Authors of a report released this week investigated the effects of high-fiber and fermented foods on the gut microbiota and immune system.

The authors recruited 36 healthy adult participants (average age, 52 years) who consumed little dietary fiber (fewer than 20 grams of fiber per day) and only one serving of fermented foods or less per day. They instructed half of the participants to add 20 grams or more of fiber per day to their baseline consumption. They instructed the other half of participants to consume six servings or more of fermented foods per day.

Participants in both groups consumed their assigned diets for 10 weeks and recorded their food and beverage intake to assess adherence to study instructions. Participants also provided blood samples for the assessment of inflammation and fecal samples for the characterization of the gut microbiome at numerous time points throughout the study.

A high-fiber diet did not reduce inflammation, but did alter the composition of the microbiota, increasing the abundance of bacteria known to metabolize dietary fibers, such as the genus Lachnospira. Higher fiber consumption also promoted greater secretion of enzymes associated with fiber metabolism and increased abundance of fiber metabolites, such as short chain fatty acids. A high-fermented food diet steadily increased microbiota diversity over time and decreased multiple markers of inflammation, including interleukin (IL)-6, IL-10, and IL-12b, among others.

These results suggest that probiotics from fermented foods increase microbiota diversity and decrease inflammation. The authors noted that the lack of immunological response in participants consuming the high fiber diet may have been due to the short duration of the intervention.

Link to full report.
Learn more about the gut microbiota and health from the authors of this report, Drs. Erica and Justin Sonnenberg, in this episode featuring Dr. Rhonda Patrick.

Vaccine-based mRNA does not pass into breast milk.

Maternal exposures during lactation influence the composition of a woman’s breast milk. Out of concern that the mRNA in mRNA-based COVID-19 vaccines could pass into breast milk and alter infant immunological development, many lactating women have declined vaccination against COVID-19 or have stopped breastfeeding prior to vaccination. Findings from a new study indicate that mRNA from an mRNA-based vaccine does not pass into breast milk.

mRNA-based vaccines contain the genetic instructions for synthesis of a single viral protein that, when injected into the body, stimulates the immune system to make antibodies against a specific target. The mRNA is housed in lipid nanoparticles to protect it, and because mRNA can’t enter a cell’s nucleus, concerns about its safety are low. Robust evidence indicates that the mRNA-based vaccines against COVID-19 are highly effective, and a small, prospective cohort study found that maternal vaccination may provide protection against COVID-19 in breastfed infants.

The current study involved seven lactating women (average age, 37 years) who were scheduled to receive either the Pfizer BioNTech or Moderna mRNA-based vaccines against COVID-19. The women provided breast milk samples prior to vaccination and between four and 48 hours afterward. The samples were chilled or frozen until they were analyzed for mRNA content via real-time quantitative polymerase chain reaction assay.

Analysis of the breast milk samples revealed that none of the samples contained detectable levels of vaccine mRNA. The authors of the study posited that if small quantities of mRNA were present in the breast milk (below the detection limits of their assay), they would likely be broken down in the infant gut. Although this was a very small study, these findings suggest that mRNA-based vaccines against COVID-19 are safe for lactating women and their infants, but further study in larger groups is warranted.

Link to full report.

Learn more about mRNA-based COVID-19 vaccines in this clip featuring Dr. Roger Seheult.
Learn more about breast milk and breastfeeding in our overview article.

Heart rate irregularities are common after recovering from COVID-19.

Although most people who have COVID-19 recover within a few weeks of becoming ill, many continue to experience symptoms for several weeks or even months after recovering. The most common long-term effects are fatigue, “brain fog,” and loss of smell or taste. A recent study using data from wearable devices found that people who have COVID-19 often experience resting heart rate irregularities long after recovery.

Wearable health monitoring devices – often simply called “wearables” – are electronic instruments that patients or consumers can wear to monitor their health, fitness, activity, or sleep. Wearables can transmit information to a physician or to the user in real time, allowing the wearer to actively participate in monitoring and maintaining their own health. Examples of wearables include smartwatches, activity trackers, and sleep monitors. Data from wearable devices may help identify people who have COVID-19.

The study investigators drew on data collected from DETECT, an app-based study of people who routinely use a smartwatch or other wearable device. The goal of DETECT is to ascertain whether changes in heart rate, activity levels (measured via step count), and sleep can identify early signs of viral illnesses, including COVID-19. They reviewed data from 875 people who developed symptoms of an acute respiratory illness and were tested for COVID-19. Of these, 234 tested positive, and 641 tested negative. They calculated deviations in the participants’ baseline heart rate by subtracting their average baseline heart rate from their daily heart rate. They grouped participants based on how many beats per minute that their heart rate deviated from baseline (less than one, one to five, or more than five beats) over a period of 28 to 56 days after developing symptoms.

The data revealed that participants who tested positive for COVID-19 took longer to return to their baseline resting heart rate, activity levels, and sleep quantity than those who did not. They tended to experience a brief period early in the course of their illness during which their heart rate was slower than normal (bradycardia), followed by a heart rate that was faster than normal (tachycardia). Their tachycardia did not resolve until approximately 79 days after initially developing symptoms. About 13 percent of the COVID-19-positive participants experienced an increase in heart rate of more than five beats per minute that persisted more than 133 days. These participants were more likely to have reported cough, body aches, and shortness of breath than those who experienced lesser deviations (less than one beat per minute) from their baseline resting heart rate. Participants’ sleep quantity returned to baseline levels about 24 days after developing symptoms, and their activity levels returned to baseline levels after about 32 days.

These findings indicate that COVID-19 elicits a wide range of long-term health effects. The authors of the study posited that these effects reflect autonomic nervous system dysfunction or ongoing inflammation, but further study in larger groups is necessary to fully understand the effects of COVID-19 illness. Learn more about how scientists are using wearable devices to diagnose COVID-19 in this episode featuring Dr. Michael Snyder.

Link to full study.

Dancing slows the progression of Parkinson’s disease symptoms.

Parkinson’s disease is a progressive, incurable neurodegenerative disorder that typically manifests later in life. It is characterized by motor features, such as tremors and a shuffling gait, but can include non-motor features as well, such as fatigue, sleep problems, and mood disorders. Findings from a new study suggest that dancing can slow the progression of both motor and non-motor symptoms of Parkinson’s disease.

A growing body of evidence indicates that physical activities that incorporate learning or skill development are particularly beneficial for people with Parkinson’s disease. Skill-based exercises, such as tennis, yoga, and non-contact boxing, involve goal-oriented movement in which accuracy is important to accomplish the desired outcome. Elements of practice, repetition, feedback, and learning are features of exercise that may be beneficial for people with Parkinson’s disease.

The study involved 16 adults (average age, 69 years) with mild severity Parkinson’s disease. Participants attended a 75-minute structured, supervised dance class once a week for three years. The dancing including both high- and low-intensity activities. Age- and disease severity-matched adults who did not participate in the dance intervention served as a reference group. The authors of the study assessed the participants’ motor and non-motor symptoms (and how those symptoms affected aspects of daily living) at various timepoints during the intervention, based on the Unified Parkinson’s Disease Rating Scale (UPDRS), a widely accepted assessment of disease severity.

The assessments revealed that participants who engaged in the dance intervention experienced no motor impairment over the three-year study period. Those who did not dance (the reference group) showed normal motor declines during that time. Participants who danced also experienced no declines motor aspects of daily living (such as those related to speech and balance) or in non-motor aspects of daily living (such as cognitive function and mood).

These findings suggest that skill-based dancing slows the progression of motor and non-motor symptoms associated with Parkinson’s disease. This was a small study, however, so more research is needed to confirm these findings. Learn more about the benefits of skill-based exercise for people with Parkinson’s disease in this clip featuring Dr. Giselle Petzinger.

Link to full report.
Learn more about Parkinson’s disease in this episode featuring Dr. Giselle Petzinger.

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