Pocket – Science Digest – April 9, 2021

Hello, friends!

We’ve got some great stories lined up for you in this issue of the Science Digest, your go-to source for the latest research on the topics most important to you. Read on to learn how…

Caffeine consumption prior to exercise improves fat metabolism.
Fasting “jump starts” dietary strategies to improve symptoms of metabolic syndrome.
Cocoa consumption protects vascular function during stress.

And much more!

In other news…

Don’t forget: We’ve got another Crowdcast live Q&A coming up TOMORROW, Saturday, April 10th, at 9:30 am PDT. 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 foundmyfitness.com/dashboard

See you there!

Rhonda and team
Science Digest – April 9, 2021
Caffeine consumption prior to exercise improves fat metabolism.

Coffee contains a wide range of bioactive compounds that influence human health. Evidence suggests that coffee consumption reduces the risk of cardiovascular disease-related deaths and certain types of cancer. Findings from a new study suggest that caffeine in coffee improves fat metabolism when consumed prior to exercise.

Caffeine is an alkaloid compound with potent stimulatory effects. Evidence indicates it improves performance in both endurance and resistance exercise. Some of these effects may be due to caffeine’s capacity to decrease the perception of effort and increase the neural actions on muscle fibers.

The triple-blind, placebo-controlled, crossover trial involved 15 healthy men (average age, 32 years) who were endurance trained but not regular consumers of caffeine. The men cycled on a stationary bike while slightly increasing the resistance every minute until they reached exhaustion. The test was performed four times, either in the morning (8 a.m.) or afternoon (5 p.m.), with each test separated by seven days. Thirty minutes prior to exercising, the men ingested either anhydrous caffeine powder from green coffee beans (3 milligrams per kilogram of bodyweight) or a placebo. The authors of the study monitored the men’s heart rate, maximal fat oxidation (and the exercise intensity at which it occurs), and respiratory function (via VO2 max) during the exercise test.

They found that maximal fat oxidation and the intensity at which it occurs exhibited a diurnal pattern, with higher values seen when the men exercised in the afternoon rather than in the morning. Caffeine potentiated the diurnal effect, increasing the men’s average maximum fat oxidation by nearly 11 percent in the morning and 29 percent in the afternoon. Caffeine also increased the exercise intensity at which the fat oxidation occurred by 11 percent in the morning and by 13 percent in the afternoon.

These findings suggest that caffeine improves fat oxidation in endurance athletes and these effects are influenced by a diurnal rhythm. Consuming caffeine in the morning maximized fat oxidation to a degree similar to that seen without caffeine in the afternoon. It is important to note that while caffeine intake may improve fat oxidation, intake late in the day can impair sleep, potentially negating some of the beneficial effects of exercise. Learn more about the effects of caffeine on sleep in this clip featuring sleep expert Dr. Matthew Walker.

Link to full study.

Fasting “jump starts” dietary strategies to improve symptoms of metabolic syndrome.

Metabolic syndrome is a constellation of conditions that includes high blood pressure, high blood glucose, excess abdominal fat, and abnormal cholesterol levels. People with metabolic syndrome are at higher risk for developing heart disease, stroke, and type 2 diabetes. Findings from a new study suggest that fasting “jump starts” dietary strategies to improve symptoms of metabolic syndrome.

The “Western diet,” also known as the Standard American Diet, is rich in processed foods, red meat, high-fat dairy products, and added sugars. It plays contributing roles in the development of metabolic syndrome. Conversely, the DASH diet – Dietary Approaches to Stop Hypertension – is rich in fruits, vegetables, whole grains, nuts, legumes, low-fat dairy products, and dietary fiber, and low in red meat and sugar-sweetened beverages. It is one of the most commonly prescribed and successful dietary patterns for managing high blood pressure and other aspects of metabolic syndrome.

Gut health also plays a role in development of metabolic syndrome. In fact, an imbalance in the number of harmful versus helpful microbes in the gut, a condition known as dysbiosis, drives many disease states. Fasting and caloric restriction induce changes in the gut microbiota to promote health.

The three-month intervention study included 71 adults between the ages of 50 and 70 years who had high blood pressure and metabolic syndrome. Half of the participants followed a modified DASH diet alone, while the other half followed a combined fasting and modified DASH diet. The modified DASH diet was a plant-based dietary program that was low in sodium, fat, and sugar. The combined fasting/DASH diet started with two calorie-restricted vegan days (no more than 1,200 calories per day), followed by a five-day liquid fast that included vegetable juices and vegetable broth (300 to 500 calories per day). Upon completion of the fast, the participants switched to the modified DASH plan. Both groups received approximately 50 hours of nutrition counseling, cooking lessons, and lifestyle coaching on exercise and stress management.

The authors of the study measured the participants’ blood pressure and other markers of metabolic health, including body weight. They also measured immune cells and assessed the microbial makeup of the participants’ gut microbiota.

Blood pressure (and the need for blood pressure medications) and bodyweight decreased among the participants following the fasting/DASH diet. The gut microbial composition of the participants following the fasting/DASH diet changed markedly during fasting, adopting a profile that was rich in microbes involved in short-chain fatty acid production, mucin degradation, and nutrient utilization. These changes in microbial composition reverted partially upon completion of the three-month DASH diet. The fasting/DASH diet also induced changes in immune cell populations, which were reversed when the participants ended their fast. Notably, fasting reduced the number of proinflammatory immune cells, whereas regulatory T cells increased. The participants who followed the DASH diet alone did not experience changes in their gut microbiota or immune cell populations.

These findings suggest that combining periodic fasting with a modified DASH diet improves blood pressure, body weight, and metabolic health in adults with metabolic syndrome better than the DASH diet alone. The participants in this study were of Caucasian-European background, potentially limiting the application of its findings. Further study is needed in a more heterogenous population.

Link to full study.

Learn more about fasting in this episode featuring Dr. Rhonda Patrick.

Cocoa consumption protects vascular function during mental stress.

Mental stress negatively affects the cardiovascular system, inducing a wide range of impairments in vascular function. In fact, exposure to even a single-episode stressor, such as a natural disaster or other traumatic situation, can trigger an acute cardiovascular event. Findings from a new study suggest that consuming cocoa protects vascular function during a stressful event.

Cocoa is derived from the cacao tree and is the principal component of chocolate. It is rich in flavanols, a class of bioactive compounds found not only in cocoa but also in apples, berries, grapes, and tea. Flavanols are potent antioxidants that exert cardioprotective effects in humans.

The cross-over intervention study involved 30 healthy young males between the ages of 19 and 36 years. After an overnight (12-hour) fast, the participants consumed a cocoa beverage prepared with 8.3 grams of either high- or low-flavanol content cocoa powder dissolved in 300 milliliters of low-nitrate water. The high-flavanol cocoa provided approximately 681 milligrams of flavanols, while the low-flavanol cocoa provided approximately 4 milligrams of flavanols. Then they took an eight-minute Paced Auditory Serial Addition Test, a measure of attention and vigilance.

At various timepoints surrounding the test, the authors of the study measured aspects of the participants’ vascular function, including heart rate, blood pressure, flow-mediated dilation, forearm blood flow, and heart rate variability. Participants repeated the test one week later with the opposite form of the beverage consumed in the first intervention.

The authors found that several measures of vascular function were improved when participants consumed the high-flavanol beverage. Flow-mediated dilation was impaired 30 minutes after the stressor in both groups of participants, but to a lesser degree among those who consumed the high-flavanol beverage. This difference was maintained even at 90 minutes after the stressor. Consuming high-flavanol cocoa improved forearm blood flow before and during the stressor. Stress-induced increases in heart rate, heart rate variability, and blood pressure were similar with both high- and low-flavanol cocoa beverages, however.

These findings suggest that cocoa, a flavanol-rich food, modulates aspects of the cardiovascular responses to stress. For an easy way to add flavanols to your diet, try this flavanol-rich smoothie.

Link to full study.

Supplemental glycine and cysteine restore glutathione levels and correct several markers of aging.

Glutathione is an antioxidant compound produced by the body’s cells. It helps prevent damage from oxidative stress caused by the production of reactive oxygen species, a key contributor to the aging process. Glutathione levels decrease with aging. Findings from a new study suggest that supplemental glycine and cysteine restore glutathione levels and correct several markers of aging.

Glycine and cysteine (commonly provided as N-acetylcysteine, or NAC) are amino acids. They play critical roles in the body’s synthesis of glutathione. Glycine and cysteine levels are typically lower in older adults and people with metabolic disease.

The authors of the study conducted a 36-week trial of combined glycine and cysteine (known as GlyNAC) supplementation in 16 healthy old (average age, 74 years) and young adults (average age, 24 years). The authors drew blood from the participants and assessed their metabolic, physical, and cognitive health at baseline and at 12, 24, and 36 weeks after the start of the intervention. Assessments included measures of mitochondrial fuel oxidation, oxidative stress, inflammation, glucose metabolism, body composition, and strength, among others. The old adults took a GlyNAC supplement (dose varied according to the participants’ bodyweight) every day for 24 weeks; the young adults did not take a GlyNAC supplement.

Twenty-four weeks of supplemental GlyNAC restored red blood cell levels of glutathione, reduced oxidative stress, and improved mitochondrial function. Markers of inflammation, endothelial dysfunction, glucose metabolism, and genomic damage decreased. Measures of cognition, strength, and body composition improved. Discontinuation of supplemental GlyNAC negated these improvements.

These findings suggest that supplemental GlyNAC provides a viable means to improve several measures of metabolic, physical, and cognitive health in older adults. This was a very small study, however, and lacked a blinded placebo group. Further study is warranted.

Link to full study.

Lutein and zeaxanthin supplementation improves visual processing in younger healthy adults.

Cognitive function, including complex executive functions like working memory and basic functions like sensory processing, progressively declines with age. While executive function loss is highly variable and easily measurable in older adult populations, younger adults usually perform at a level consistent with their peers, which makes studying cognitive decline in younger adults difficult. In a 2014 study, researchers measured visual processing ability in young adults before and after supplementation with lutein and zeaxanthin.

Visual processing refers to the brain’s ability to utilize and interpret visual information. Because visual processing utilizes similar brain architecture as more complex tasks, such as working memory, it is a useful measure in assessing brain health and cognitive decline.

Lutein and zeaxanthin are carotenoid pigments found in green leafy vegetables and eggs. These yellow-hued compounds accumulate in the retina and throughout the brain and perform light-absorbing, antioxidant, and anti-inflammatory functions. Animal research has demonstrated that the density of these pigments in the eye is a good indicator of their density in the brain, providing researchers a non-invasive means to measure the relationship between pigmentation and cognitive function. Higher pigment density in the eye has been associated with better cognitive performance and visual processing speed in older adults with or without cognitive decline.

Researchers measured the baseline visual processing speed and retinal concentration of lutein and zeaxanthin in healthy young adults (average age, 22 years). They assigned participants to consume either placebo, zeaxanthin only (20 milligrams), or a combination of zeaxanthin (26 milligrams), lutein (8 milligrams), and mixed omega-3 fatty acids (190 milligrams) per day for four months. They measured retina pigmentation and visual processing speed again following the intervention.

The authors reported a moderate, yet statistically significant, relationship between baseline retinal pigment levels and visual processing speed. Following the intervention, both supplement groups demonstrated a significant increase in retinal pigmentation compared to placebo. Finally, participants in the supplement groups also performed 12 percent better on the critical flicker fusion test and decreased visual motor reaction time by 10 percent, two measures of visual processing.

The authors concluded that lutein and zeaxanthin supplementation may be an effective means to increase visual processing speed, even in young healthy adults.

Link to full study.

Omega-3 fatty acids reduce inflammation and cardiovascular disease risk.

Treatment strategies for cardiovascular disease that reduce inflammation are an important area of research. The omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) both reduce inflammation by decreasing pro-inflammatory cytokines and increasing anti-inflammatory compounds. In a recent report, investigators tested the effects of EPA and DHA supplementation on vascular inflammation, a mediator of atherosclerosis.

Omega-3 fatty acids are found in certain types of fish and seafood. In epidemiological research, higher fish consumption is associated with lower risk of cardiovascular disease and death. In clinical trials, EPA supplementation reduced major cardiovascular events in those with high cholesterol; however, the role of inflammation in this research is unclear.

The investigators conducted three experiments in humans and mice. In the first experiment, healthy adults (average age, 38 years) consumed 4 grams of either EPA only, DHA only, EPA + DHA (2:1 ratio), or a placebo for 30 days. They completed a health assessment and gave a sample of blood before and after treatment. The researchers used the serum collected from participants to culture human vascular cells and measured the response of those cells to an inflammatory stimulus.

In the second experiment, which focused on acute inflammation, researchers treated mice with EPA (600 milligrams per kilogram of body weight), DHA (600 milligrams per kilogram body weight), olive oil, or no treatment daily for 30 days. They measured several markers of vascular inflammation and blood lipids before and after treatment.

In the third experiment, which focused on chronic inflammation, the researchers fed mice a diet known to promote heart disease in mice for 16 weeks. During the final eight weeks of the diet, they treated the mice with the same EPA, DHA, olive oil, or no treatment conditions as the second experiment and measured markers of atherosclerosis and blood lipids.

In the human study, EPA supplementation reduced markers of vascular inflammation better than DHA only or fish oil. In mice from the second experiment, both EPA and DHA supplementation significantly reduced multiple markers of vascular inflammation without affecting cholesterol and triglyceride levels. EPA was more effective in reducing inflammation than DHA. In mice from the third experiment, both DHA and EPA reduced cholesterol and triglyceride levels, with DHA being more effective. EPA supplementation reduced multiple markers of vascular inflammation; however, neither treatment improved markers of atherosclerosis.

The authors concluded that high-dose omega-3 supplementation can reduce vascular inflammation at early and late stages of cardiovascular disease. They also noted that the small sample size of their study may have limited their results and suggested that EPA supplementation should be tested in larger trials.

Link to full study.
Learn more about cholesterol and atherosclerosis in this episode featuring expert Dr. Ronald Krauss.

Sunlight is more effective at inactivating the SARS-CoV-2 virus than predicted.

As the global COVID-19 pandemic continues, new ways of battling SARS-CoV-2, the virus that causes the disease, are needed, especially in areas where vaccine distribution is low. Sunlight is an inexpensive and widely-available tool for disinfection, but may require too much time to be effective. Researchers have discovered a discrepancy between the expected and actual rates of ultraviolet (UV) sterilization for the SARS-CoV-2 virus, although the reason for this discrepancy is unknown.

Sunlight contains a spectrum of wavelengths of UV radiation including UVA and UVB light, which directly damage viral RNA and inactivate viruses. The time it takes for sunlight to sterilize a given virus depends on the size of the viral genome and the wavelength of light. In a 2005 report from the United States Army, researchers created an equation for calculating the sunlight sterilization times for various viruses in different geographic locations.

The same group of researchers used their model to estimate the expected time to 90 percent sterilization of the SARS-CoV-2 virus for different locations within and outside the United States during different seasons. A second group of researchers from the National Biodefense Institute conducted an experimental study in which they measured the 90 percent sterilization time of the SARS-CoV-2 virus suspended in simulated saliva or laboratory media and dried on stainless steel using artificial UVB light.

When compared to the estimates produced by the first group of researchers, actual time to sterilization for the SARS-CoV-2 virus in simulated saliva was eight times faster than expected. When exposed to UV light at a level one would expect at a latitude of 40 degrees north at noontime during the summer, the 90 percent sterilization time was 6.8 minutes. Sterilization time for the virus in laboratory media was three times faster than expected at 14.3 minutes.

Both groups of researchers concluded that sunlight could be an important tool in fighting the spread of the SARS-CoV-2 virus, but factors like latitude, season, and weather all affect the time required for sterilization. They cautioned that low sunlight exposure in many northern cities during the winter months may lengthen the 90 percent sterilization time. Further research is needed to understand why sunlight sterilization is more effective against the SARS-CoV-2 virus than originally estimated.

Link to full study.

Previous COVID-19 infection or vaccination confers long-term protection against future severe disease outcomes.

Following infection with SARS-CoV-2 (the virus that causes COVID-19), the adaptive immune system produces neutralizing antibodies that attack the virus and prevent further illness in those who recover. Vaccination provides another means of developing long-lasting immunity. However, neutralizing antibody concentrations decline with time following vaccination or previous infection. Authors of a recent report created a model for predicting the decline of neutralizing antibody concentrations over time and what is needed to maintain long-term immunity.

Those who recover from SARS-CoV-2 infection have an estimated 89 percent protection from reinfection, while vaccine protection estimates range from 50 to 95 percent. There is concern that new variants may bypass immune protection in previously infected or vaccinated people. Predictive models of immunity may guide the distribution of vaccines and vaccine boosters as the pandemic progresses.

The researchers combined and standardized data from trials studying the neutralizing antibody response to seven different vaccines and data from a group of recovered participants. They created a model based on previous research of the influenza virus to estimate the concentration of antibodies needed to provide 50 percent protection against SARS-CoV-2 infection. Lastly, they used their model to predict the efficacy of a new vaccine released in March 2021.

The authors reported that the antibody concentration needed to provide 50 percent protection is just 20 percent of the average concentration found in recovered people three to four months following infection. The concentration needed to prevent severe COVID-19 disease is only 3 percent of post-infection levels. The investigators’ model predicted a significant decline in antibody concentration over 250 days following vaccination; however, the predicted concentration was still high enough to prevent severe disease. The model was also highly effective in predicting the efficacy of a new vaccine (79 percent estimated efficacy, 81 percent reported efficacy).

The authors noted that methods for measuring neutralizing antibody activity and recovery status varied widely among the studies they used to create the model, potentially decreasing its accuracy; however, early use of the model provided accurate results. This study has not yet been peer-reviewed.

Link to study abstract.

Afternoon exercise improves insulin tolerance more than morning exercise.

The circadian rhythm is controlled by a central clock in the brain and by peripheral clocks in skeletal muscle, adipose tissue, and other organs. Together, these clocks coordinate the expression of genes related to a variety of metabolic processes with daily light, eating, and activity cycles. New research suggests that exercising in the afternoon maximizes metabolic benefits due to circadian-driven cycles.

While light is the main driver of the central circadian clock in the brain, peripheral clocks are responsive to a number of environmental signals such as eating and exercise. When these activities are out of sync with normal light/dark cycles, as seen with shift work, metabolic dysfunction occurs. Previous research in humans has reported severely impaired glucose and insulin regulation with circadian disruption.

The investigators recruited a group of 32 males (average age, 58 years) who had type 2 diabetes or were at risk for developing type 2 diabetes. Participants completed 12 weeks of combined aerobic and resistance training in the morning (8 a.m. to 10 a.m.) or afternoon (3 p.m. to 6 p.m.). The researchers measured insulin tolerance, body composition, and exercise performance before and after the intervention.

Insulin sensitivity in participants who exercised in the afternoon improved by 34 percent, while insulin sensitivity in the morning exercising group improved only 3 percent. The afternoon group also experienced a significantly greater reduction in fasting glucose levels, fat mass, percent body fat, and exercise performance. Although it wasn’t statistically significant, afternoon exercise also tended to improve glucose output from the liver, another marker of metabolic health.

The authors concluded that exercising in the afternoon improved insulin tolerance, body composition, and exercise performance to a greater extent than morning exercise in those with metabolic dysfunction. The authors speculated that circadian cycles in skeletal muscle or cycles in body hormone levels may be the cause of this effect, although further research is needed to fully understand the impact of exercise timing on metabolism.

Link to full study.
Learn more about the importance of circadian rhythms in this episode featuring expert Satchin Panda.

Excess sugar intake in early life impairs memory in adulthood via changes in the gut microbiota.

A healthy gut microbiota is important for cognitive function at any age, but especially during development. Poor dietary quality in early life negatively impacts the composition of the gut microbiota and impairs cognitive functioning; however, the mechanisms that drive these changes are unclear. Authors of a new report detail the functional relationship between detrimental gut microbes and hippocampal memory in rats exposed to excess sugar during adolescence.

Germ-free mice, which are born and raised in a sterile environment, demonstrate impaired brain development compared to mice with a normal gut microbiota. This suggests that microbiota composition in early life may impact cognitive function in adulthood. Dietary strategies that minimize sugar intake may improve microbiota quality and maximize developmental potential in children and adolescents.

The investigators conducted a two-part experiment in rats. In the first experiment, they fed sugar-sweetened water or plain water to juvenile rats for 11 weeks. They sequenced bacterial DNA from the rats’ fecal samples to measure changes in the gut microbiota. In the second experiment, the researchers treated juvenile rats with antibiotics or a placebo for seven days. Then they treated one half of the antibiotic group with a bacterial culture of Parabacteroides distasonis and Parabacteroides johnsonii, while the other half received a placebo. In both experiments, rats completed a series of tests to measure memory function in adulthood. Finally, the researchers measured gene expression in the hippocampus, one of the major memory centers of the brain.

Adult sugar-fed rats exhibited impaired performance on memory tasks associated with the hippocampus, but not other memory centers. The authors found that sugar consumption led to an increase in Parabacteroides bacteria in the gut that correlated with impaired hippocampal function. When antibiotic-treated rats were given Parabacteroides distasonis and Parabacteroides johnsonii as a supplement in adolescence, they exhibited similar deficits in memory performance in adulthood as sugar-fed rats. Sugar consumption altered the expression of genes associated with neurotransmitter signaling, while Parabacteroides treatment altered genes associated with metabolic function, neurodegenerative disease, and dopamine signaling.

The authors of this comprehensive report concluded that early-life dietary factors such as sugar consumption impact brain development and may impair memory via changes in the gut microbiota.

Link to full study.
Learn more about sugar and its effects on the brain and body in this podcast featuring Dr. Rhonda Patrick.

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