Science News Digest – April 23, 2021

Hey, friends!

We’ve got a great lineup of stories in this issue of our Science Digest, handpicked just for you, our Premium Members. Read on to learn how…

Regular exercise may reduce COVID-19 risk.
Omega-3 fatty acids improve clinical outcomes in COVID-19.
One 60-minute bout of aerobic exercise increases mitochondrial metabolism in sedentary adults.

And much more!

ICYMI: We released a new video this week about the brain-protective effects of sleep. Be sure to check it out!

In other news: We’ve got another Crowdcast live Q&A coming up Saturday, May 1st, at 9:30 am PDT. The code for this event is sulforaphane. Remember, you can always access the most recent event code and Q&A calendar by visiting your dashboard at


Rhonda and team
Science Digest – April 23, 2021
Regular exercise may reduce COVID-19 risk.

Regular physical activity promotes physical and mental well-being and reduces the risk of developing chronic diseases such as cardiovascular disease and cancer. Findings from a new study suggest that regular physical activity also reduces the risk of developing COVID-19.

Most international public health organizations recommend that adults of all ages engage in at least 150 minutes of moderate intensity aerobic physical exercise or at least 75 minutes of vigorous intensity aerobic physical exercise each week, or an equivalent combination of both. Most adults fall far short of these recommendations, however.

The retrospective observational study involved more than 48,000 patients who had been diagnosed with COVID-19 between January and October 2020. The study investigators obtained data regarding the patients’ physical activity levels in the two-year period between March 2018 and March 2020 via their electronic health records. They categorized the patients as “consistently inactive” (zero to 10 minutes per week), having “some activity” (11 to 149 minutes per week), or “consistently meeting guidelines” (150+ minutes per week).

Statistical analysis revealed that COVID-19 patients who were consistently inactive were 2.26 times more likely to be hospitalized; 1.73 times more likely to be admitted to the intensive care unit (ICU), and 2.49 times more likely to die due to COVID-19 than patients who were consistently meeting guidelines. Engaging in some activity mitigated risk slightly: Consistently inactive patients were 1.2 times more likely to be hospitalized, 1.1 times more likely to be admitted to the ICU, and 1.32 times more likely to die from COVID-19 than patients who were doing some physical activity.

These findings suggest that physical activity decreases the risk of developing COVID-19 and underscore public health messaging to promote regular physical activity. For people who are unable to regularly engage in exercise due to physical limitations or injury, sauna use may provide an alternative to tapping into the many metabolic and cardiovascular benefits of exericse. Heat exposure during sauna use mimics many of the physiological responses to exercise, including immune-boosting effects. Learn more about sauna use in our overview article.

Link to full study.

Omega-3 fatty acids improve clinical outcomes in severe COVID-19.

Nutritional status plays critical roles in fighting infections, influencing not only how well the body’s immune system works but also how pathogens behave in the body. Findings from a new study suggest that omega-3 fatty acids improve clinical outcomes in critically ill patients with COVID-19.

Omega-3 fatty acids, such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-linoleic acid (ALA) are essential nutrients. They participate in a wide range of physiological functions, including immune responses. Evidence suggests that omega-3 fatty acids stabilize cell membranes, regulate immune function, impair hyper-inflammatory reactions, and reduce severe outcomes associated with infections, such as systemic inflammatory response syndrome and multiple organ dysfunction syndrome.

The double-blind, randomized clinical trial involved 101 critically ill hospitalized patients (average age, 65 years) diagnosed with COVID-19. Twenty-eight of the patients received 1,000 milligrams of supplemental omega-3 fatty acids via enteral feeding daily for two weeks, commencing 24 hours after admission to the intensive care unit. The supplement provided 400 milligrams of EPA and 200 milligrams of DHA. The remainder of the participants received enteral feeding without supplemental omega-3 fatty acids. The study investigators collected the participants’ anthropometric data, medical histories, dietary records, and biochemical measures of respiratory and renal function.

The one-month survival rate was 21 percent among the patients who received the supplemental omega-3 fatty acids, versus 3 percent among those who did not receive the supplement. The supplemented group also had improved markers of respiratory and renal function, including higher arterial pH, bicarbonate, and urinary output levels and lower blood urea-nitrogen, creatinine, and potassium levels.

These findings suggest that supplemental omega-3 fatty acids improve respiratory and renal function in critically ill patients with COVID-19. Although the study was sufficiently powered, the sample size was small, necessitating future studies with larger groups.

Link to full study.
Learn more about caring for critically ill COVID-19 patients in this episode featuring Dr. Roger Seheult.

One 60-minute bout of aerobic exercise increases mitochondrial metabolism in sedentary adults.

Exercise puts a demand on skeletal muscle cells to produce energy at a faster rate than at rest. To do this, the body increases the delivery of fats to the muscle mitochondria while increasing the mitochondrial capacity to metabolize fats, a process called beta-oxidation. Researchers of a new study aimed to illuminate the cellular mechanisms of mitochondrial fat metabolism following moderate intensity aerobic exercise.

Mitochondria are cellular structures responsible for the production of energy in the form of adenosine triphosphate (ATP). The inner membrane of mitochondria possess a series of enzymes called the electron transport chain. These enzymes transfer electrons from carbohydrates and fats (as well as proteins and nucleic acids to a lesser extent) to the final enzyme in the chain that produces ATP. Electron transfer flavoprotein is an enzyme in this chain that transfers electrons from fats, specifically. The authors of this report have previously presented data demonstrating an increase in electron transfer flavoprotein activity in mice after aerobic exercise training.

The investigators recruited fifteen healthy sedentary adults (average age, 28 years) with a normal body mass index. Participants completed one hour of cycling at 65 percent of their maximum aerobic capacity on one day and rested the next day. The researchers collected biopsies from the participants’ thigh muscle after they had rested and 15 minutes after they exercised. They analyzed the muscle mitochondria for the abundance of electron transfer flavoprotein activity and for the metabolism of fats and nonfat fuel sources.

Following exercise training, mitochondrial metabolism of fats and non-fat sources increased, although this relationship was not statistically significant. Also noted was a six percent increase in hydrogen peroxide, which is a byproduct of fat metabolism that damages cells. Although fat metabolism increased, the authors reported no increase in electron transfer flavoprotein activity abundance.

They authors concluded that just one session of moderate intensity aerobic exercise in sedentary adults increases energy metabolism of both fats and non-fat sources. They suggested future research would include a larger sample of participants.

Link to full report.
Learn how to maximize mitochondria metabolism with magnesium in this video.

Spermidine improves cognitive function in humans.

Age-related changes in the brain drive cognitive impairment, which in turn alters memory formation and promotes mitochondrial dysfunction. A recent study demonstrates that spermidine improves cognitive function in humans.

Spermidine is a dietary compound found in a number of foods, including wheat germ, cauliflower, broccoli, mushrooms, amaranth, a variety of cheeses (especially aged cheeses), and soybean products, such as natto. First identified in semen, spermidine demonstrates anti-aging properties in animal studies, likely due to its capacity to induce autophagy – the process by which the body clears dead and damaged cells. Human studies have demonstrated an association between dietary spermidine intake and increased survival.

The authors of the study investigated the effects of spermidine supplementation in various models of aging. They fed aged mice spermidine in their drinking water and measured the compound’s appearance in the animals’ brains. The compound appeared in brain tissue within one week of administration and continued to accrue to roughly one-third of bloodstream levels. Spermidine altered protein synthesis in the animals’ brains via its actions on hypusine, an amino acid that is essential for the function of ELF5A, a protein that plays roles in mammalian protein production. Mice that received spermidine exhibited improvements in spontaneous behavior, exploration, maze completion, and other measures of cognitive function.

The authors also fed fruit flies spermidine and found that the compound improved mitochondrial function and reduced age-induced memory impairments. These improvements were mediated by Atg7, PINK, and parkin – proteins that play key roles in autophagy and mitophagy.

Then the authors reviewed epidemiological data from food frequency questionnaires and cognitive tests completed by participants in the Bruneck Study, a prospective cohort study of adults living in Bruneck, Italy. They found that higher intake of spermidine-rich foods was associated with greater cognitive function in aging.

These findings suggest that dietary spermidine exerts neuroprotective effects in several model of aging, likely due to the compound’s effects on mitochondrial health. Dietary interventions that promote spermidine-rich foods may be useful in slowing cognitive decline in humans.

Link to full study.
Learn more about dietary spermidine and autophagy in this clip featuring Dr. Guido Kroemer.

A Mediterranean dietary pattern supplemented with low to moderate amounts of beef decreases LDL cholesterol.

The Mediterranean dietary pattern, which is low in saturated fats and high in unsaturated fats, is widely-recognized as a heart-healthy diet when compared to the standard American dietary pattern, which is high in saturated fats. Red meat is traditionally minimized in the Mediterranean dietary pattern to less than 120 grams (about four ounces) per week – roughly the size of a small burger patty; however, this recommendation is largely based on epidemiological evidence, not interventional trials. Authors of a new report aimed to determine the dose-dependent effects of lean beef consumption as part of a Mediterranean dietary pattern on heart disease risk.

Recent research suggests that lean, unprocessed red meat can be included in a heart-healthy dietary pattern. One randomized clinical trial found that consumption of a Mediterranean dietary pattern supplemented with 500 grams (about 17 ounces) of red meat per day over five weeks reduced total and LDL cholesterol.

Fifty-nine generally healthy participants of varying weight status between the ages of 30 and 65 years completed the trial. Participants consumed a Mediterranean dietary pattern (8 percent saturated fat) supplemented with either 0.5, 2.5, or 5.5 ounces of lean, unprocessed beef per 2,000 calories consumed per day. As a comparison diet, participants also consumed an American dietary pattern (12 percent saturated fat). All participants consumed each diet for four weeks in a randomized order and had their blood drawn at multiple time points for cholesterol testing.

Compared to the American dietary pattern, all three Mediterranean dietary patterns significantly reduced LDL cholesterol (0.5 ounces: −10.3 milligrams per deciliter; 2.5 ounces: −9.1 milligrams per deciliter; 5.5 ounces: −6.9 milligrams per deciliter). The authors also reported reductions in LDL particle number for all three Mediterranean dietary patterns, although this reduction was significant for the diets supplemented with 0.5 ounces or 2.5 ounces of red meat but not 5.5 ounces. All four diets resulted in reductions of HDL cholesterol and HDL particle number compared to baseline.

The researchers concluded that the cholesterol-lowering effects of a Mediterranean dietary pattern were not diminished by the inclusion of up to 2.5 ounces of lean, unprocessed beef. They noted that future research should test a similar diet in patients with worse health status than this generally healthy population.

Link to full report.

Fish oil supplementation improves testicular function in young males without infertility.

Evidence suggests that sperm quality in males over the past 50-70 years has declined, likely due to a combination of dietary and lifestyle factors and exposure to endocrine-disrupting chemicals. For example, diets rich in processed meats, full fat dairy, and sugar-sweetened beverages are associated with poor sperm quality, whereas diets rich in vitamins, minerals, and unsaturated fats improve sperm quality and fertility. Results of a recent observational study demonstrate the effects of fish oil supplementation on sperm quality and testicular function in healthy young males.

Infertility affects 15 percent of couples, with male and female reproductive dysfunction contributing equally to infertility rates. Previous epidemiological research has revealed an association between fish consumption and better sperm quality in males seeking infertility treatment. Fish and fish oil supplements are an excellent source of omega-3 fatty acids, a type of polyunsaturated fat with numerous anti-inflammatory and health-promoting properties. Two previous randomized, controlled trials have reported increased antioxidant capacity and decreased DNA fragmentation in the sperm of males experiencing infertility who were supplemented with omega-3 fatty acids. However, the effects of supplementation in men without infertility is unknown.

The investigators recruited more than 1,600 male participants (average age, 19 years) who presented for a physical examination for military service in the Netherlands. Participants volunteered to provide a blood sample for the measurement of sex hormones and a semen sample. Finally, they answered a questionnaire about health, lifestyle, diet, and dietary supplement use over the previous three months.

Only 5.8 percent of the participants had consumed fish oil supplements in the previous three months and only 3.1 percent consumed fish oil supplements for more than 60 days over the previous three months. Participants who supplemented with fish oil less than 60 days had increased sperm volume and testicle size compared to those who did not supplement. Participants who supplemented for more than 60 days had even greater sperm volume and testicle size. Participants who supplemented with fish oil also had a 20 percent lower concentration of follicle-stimulating hormone and a 16 percent lower concentration of luteinizing hormone, an indication of better testicular cell function and greater capacity for sperm production.

The authors concluded that fish oil supplementation improves testicular function in males without infertility, even after taking into account the intake of other dietary supplements. Because this study did not take dose into account, randomized clinical trials are needed to further examine this relationship.

Link to full report.

EPA and DHA supplementation increases serum testosterone levels in males with overweight and obesity.

Long-chain omega-3 fatty acids, such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), increase serum testosterone levels in mice, although the mechanisms that drive these benefits are unclear. While omega-3 fatty acids improve cellular function, omega-6 fatty acids serve as precursors to pro-inflammatory cytokines, such as arachidonic acid, which damage cells. Findings from a recent report detail the effects of long-chain omega-3 fatty acids and omega-6 fatty acids on serum testosterone levels in adults with overweight and obesity.

Omega-3 fatty acids are essential nutrients found in the oils of fatty fish, such as salmon. In humans, they increase cellular membrane flexibility, which improves cellular function. Omega-6 fatty acids are the primary fats in most vegetable oils, such as corn oil. In excess, omega-6 fatty acids can be harmful to health. Leydig cells, located in the testicles, produce testosterone when stimulated with luteinizing hormone. Evidence from studies in mice suggest that long-chain omega-3 fatty acids incorporate into the plasma membranes of Leydig cells increasing their responsiveness to luteinizing hormone and increasing testosterone synthesis.

The authors recruited 22 males with overweight and obesity who did not have type 2 diabetes to participate in the study. Participants consumed either fish oil (providing 860 milligrams of DHA and 120 milligrams of EPA per day) or a placebo (1 gram of corn oil per day) for 12 weeks. They provided blood samples for the analysis of sex hormones and metabolic markers and completed questionnaires about health, diet, dietary supplement use, and other lifestyle factors.

Fish oil supplementation significantly increased serum testosterone concentrations, even after taking into account age and body mass index. This increase in testosterone occurred with an increased concentration of omega-3 fatty acids in the membranes of red blood cells, an indicator of the membrane composition of Leydig cells. The researchers reported an even stronger association between increased testosterone and decreased omega-6 fatty acid concentration in red blood cell membranes. They also noted improvements in insulin sensitivity among the supplemented group compared to the placebo group.

These findings demonstrate that long-chain omega-3 fatty acid supplementation increased serum testosterone levels in males with overweight and obesity. The authors noted that their report is a secondary analysis of a larger clinical trial and that future research with a larger sample of participants is prudent.

Link to full report.

Sugar-sweetened beverage consumption is associated with lower testosterone levels in younger adult males.

Sugar-sweetened beverages are the largest source of added sugar in the American diet. The over consumption of sugar-sweetened beverages is linked to insulin resistance and to multiple diseases including obesity, type 2 diabetes, cardiovascular disease, and gout. One group of investigators aimed to determine the relationship between sugar-sweetened beverage consumption and serum testosterone.

Testosterone is essential for masculine development during puberty and reproductive capacity in adult males. Epidemiological evidence has revealed higher serum testosterone levels in males without diabetes compared to males with diabetes and in active males compared to sedentary males. Previous clinical research has reported a relationship between sugar-sweetened beverage consumption and decreased sperm motility and fertility; however, its relationship with testosterone has not yet been demonstrated.

The authors reviewed data from the 2011-2012 National Health and Nutrition Examination Survey, a large-scale survey research project that tracks the health and nutrition of adults and children in the United States over time. Research staff for this project administer an interview to participants to collect dietary and demographic information and medical, dental, and laboratory tests to collect physiologic measures.

The investigators of this report specifically chose a sample of younger males (between ages 20 and 39 years) because this is the period when fertility is highest. They categorized participants (545 males total) into four levels of sugar-sweetened beverage consumption with participants in the lowest level consuming 137 calories of sugar-sweetened beverages or less per day and the highest consuming 442 calories or more per day.

Ninety percent of participants had a normal testosterone level, defined as greater than 231 nanograms per deciliter. Participants in the highest level of sugar-sweetened beverage consumption were more than twice as likely to have low serum testosterone. After taking into account other factors, including age, race/ethnicity, poverty/income, tobacco and alcohol consumption, and physical activity the authors also found that participants with overweight and obesity were nearly four times more likely to have low serum testosterone compared to lean males, independent of sugar-sweetened beverage consumption.

This report demonstrates that sugar-sweetened beverage consumption and higher body mass index were both associated with lower testosterone levels in males. These associations were independent of each other and not due to other demographic and lifestyle factors.

Link to full report.

Testosterone levels drop in response to glucose consumption regardless of weight status or glucose tolerance.

Hypogonadism, a disorder in which dysfunction of the ovaries or testes results in the diminished production of sex hormones, is a growing concern, demonstrated by a marked increase in prescriptions for testosterone replacement. Previous research has reported lower serum testosterone in males with type 2 diabetes and metabolic disease. To expand on this observational research, investigators aimed to determine the effects of a glucose challenge on testosterone levels.

Testosterone levels change in response to food intake, which activates the secretion of messenger molecules from the hypothalamus that affect the reproductive organs. While some studies have reported a decrease in serum testosterone in response to glucose intake, others have found an increase in serum testosterone in response to a dose of insulin. The mechanisms underlying the relationship between glucose intake and testosterone levels have yet to be illuminated.

The authors conducted their investigational study with a group of 74 healthy males (19 to 74 years old) of varying weight status who had not been diagnosed with type 2 diabetes. The researchers administered an oral glucose tolerance test in which participants consumed 75 grams of glucose, which is roughly the amount of sugar in two cans of sugar-sweetened soda, and had their blood drawn before consuming the glucose (baseline) and at 30, 60, 90, and 120 minutes afterward. The researchers also collected blood for the measurement of testosterone and other hormones, including luteinizing hormone, which stimulates testosterone production.

At baseline, 57 percent of the participants had normal glucose tolerance, 30 percent had impaired glucose tolerance, and 13 percent met the criteria for a diagnosis of type 2 diabetes. Glucose intake resulted in lower serum testosterone at all time points following glucose consumption, with an average maximum decrease of 25 percent from baseline levels. The authors reported no changes in plasma concentrations of luteinizing hormone or cortisol and a significant decrease in plasma levels of the hormone leptin. Finally, they reported no differences in testosterone response between men of varying glucose tolerance or weight status.

The investigators concluded that a challenge of 75 grams of glucose significantly decreased serum testosterone levels, although the mechanisms that drove the decrease are still unclear, given that no changes in luteinizing hormone were found.

Link to full report.

Sugar exposure reduces production of sex hormone-binding globulin, a predictor of metabolic health.

Obesity and metabolic disease are associated with reduced fertility and alterations in several markers of reproductive health, including plasma concentrations of sex hormone-binding globulin. Low levels of sex hormone-binding globulin are common in those with obesity and are predictive of cardiovascular disease and type 2 diabetes risk, although it is unclear how glucose and insulin regulation affect sex hormone-binding globulin levels. A group of investigators recently performed a series of experiments with the aim of identifying mechanisms of sugar metabolism and sex hormone-binding globulin production.

Sex hormone-binding globulin, which is produced by liver, transports sex hormones in the blood and regulates their uptake by sensitive tissues. Hepatocyte nuclear factor-4α, also produced by the liver, stimulates sex hormone-binding globulin production and increases serum testosterone by decreasing its half-life. De novo lipogenesis, the process by which the liver converts excess sugar into fatty acids, suppresses hepatocyte nuclear factor-4α activation and sex hormone-binding globulin production.

In the first experiment, the researchers used transgenic mice whose genomes had been altered to express the human sex hormone-binding globulin gene. They fed these mice a diet high in either sucrose, glucose, or fructose (three types of simple sugars) for one week and measured blood levels of sex hormone-binding globulin. In a second experiment, the researchers exposed human liver cells to varying amounts of insulin and to high concentrations of either glucose or fructose and measured gene expression. Finally, they exposed the same type of liver cells to varying concentrations of glucose and fructose and to the fatty acid palmitate and measured gene expression.

After five days a high fructose diet reduced sex hormone-binding globulin levels in the mice by fructose 80 percent. Sex hormone-binding globulin levels decreased by 40 percent on a high glucose diet and 50 percent on a high sucrose diet. Insulin exposure did not affect sex hormone-binding globulin production in mice. In liver cells, glucose and fructose exposure over five days reduced sex hormone-binding globulin accumulation by 50 percent. This change corresponded to a three- to fourfold reduction in the expression of hepatocyte nuclear factor-4α. Additionally, glucose or fructose exposure over five days resulted in a two- to threefold increase in palmitate production (due to de novo lipogenesis), which corresponded to reductions in sex hormone-binding globulin. Finally, exposure to varying amounts of palmitate over five days reduced hepatocyte nuclear factor-4α expression and sex hormone-binding globulin production.

The authors of this comprehensive study concluded that excess sugar intake resulted in increased de novo lipogenesis, which led to a suppression of hepatic HNF-4α activity, which in turn attenuated sex hormone-binding globulin expression. This work provides a detailed explanation of why sex hormone-binding globulin is a sensitive biomarker of metabolic syndrome and why simple sugars, especially fructose, decrease fertility.

Link to full report.

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