Hi, Premium Members!
We’ve lined up some really interesting stories for this issue of the Science Digest, curated just for you.
Read on to learn how…
Irisin, a muscle hormone, mediates the neuroprotective effects of exercise.
Sauna use may increase muscle and bone mass.
Vaccination against COVID-19 cuts risk of long-term complications from breakthrough infection by half.
And more!
In other news, we released a brand-new podcast episode today, featuring omega-3 expert Dr. Bill Harris. You won’t want to miss this one.
And we have another Crowdcast live Q&A coming up Saturday, October 2, at 9:30 am PDT. The code for this event is vitaminc. Remember, you can always access the most recent event code and Q&A calendar by visiting your dashboard at foundmyfitness.com/dashboard.
Enjoy!
Rhonda and team
Science Digest – September 10, 2021
Irisin, a muscle hormone, mediates the neuroprotective effects of exercise.
Aging causes brain changes that promote cognitive decline, even in people who do not have Alzheimer’s disease or dementia. However, lifestyle factors like diet and exercise have significant influence over the rate of decline. Previous research has shown that exercise improves brain health and cognitive function during aging. A new report details the role of the muscle hormone irisin in the neuroprotective effects of exercise.
Irisin, a type of myokine, is a hormone secreted from muscle in response to exercise. Previous research has shown that irisin may mediate some of the beneficial effects of exercise on the brain by stimulating the production of brain-derived neurotrophic factor (BDNF), a growth factor that increases neuroplasticity. Irisin is a fragment of the prohormone FNDC5, which is attached to the membranes of muscle cells. During exercise, irisin is cleaved from FNDC5 and circulates throughout the body to induce adaptations to exercise.
The authors used mice of varying ages that lack the genes necessary to produce FNDC5, called knock-outs, and genetically-normal mice, called wild-type. Both groups of mice completed exercise testing to measure balance, grip strength, endurance, and motor coordination; a water maze test to measure spatial learning ability and memory; and an open field test to measure locomotor activity levels, anxiety, and willingness to explore. In order to study the effects of irisin supplementation, the investigators conducted a second experiment in which they administered exogenous (i.e., made outside the body) irisin to a strain of mice who develop an Alzherimer’s-like dementia at an early age due to loss of FNDC5 function. The investigators measured structural and psychological changes in the brain throughout both experiments.
Both knock-out and wild-type mice exercised the same amount during testing. However, unlike the wild-type mice, knock-out mice did not show exercise-induced improvements in spatial learning and memory. Aged knock-out mice had more cognitive decline than wild-type mice and were less likely to prefer novel objects, a behavior associated with loss of function in the hippocampus, the brain region most associated with memory loss in dementia. Indeed, aged knock-out mice showed abnormal neuronal activation patterns in the dentate gyrus, a structure within the hippocampus that contributes to memory formation.
In contrast to knock-out mice and sedentary wild-type mice, wild-type mice that exercised had increased dendritic complexity and length in the dentate gyrus. This demonstrates the ability of exercise to improve neuronal structure and function in brain areas associated with memory through mechanisms involving irisin. Regular injections with exogenous irisin significantly improved performance on spatial learning and memory tasks in mice with Alzheimer’s-like dementia compared to untreated mice. These improvements may have been caused by dampening of overactive glial activity, leading to reduced inflammation.
Taken together, these data suggest that irisin is essential for mediating the beneficial effects of exercise on cognitive function. The authors concluded that these data also demonstrate the efficacy of exogenous irisin administration in regulating cognitive function in mice with Alzheimer’s-like dementia, providing support for future use of irisin therapies in humans with dementia.
Link to full publication.
Learn more about how exercise increases BDNF and protects the brain from depression in this video with Rhonda.
Sauna use may increases muscle and bone mass.
Aging induces many alterations in body composition, even in the absence of changes in body weight. Typically, as a person ages, their fat mass increases, and their muscle mass and bone mineral density decrease. Findings from a recent study suggest that sauna use increases muscle and bone mass.
Sauna use involves transient exposure to heat, stressing the body and eliciting a wide range of protective responses. Evidence indicates that heat stress may promote muscle growth via activation of pathways involved in protein synthesis and drive osteogenesis (bone formation) via activation of heat shock proteins.
The intervention study involved 23 healthy young males (average age, 20 years). Participants completed questionnaires regarding their physical activity and nutritional intake. Half of the participants engaged in 12 sauna sessions, performed three times per week for four weeks. Each session consisted of five sets of 10-minute exposures at 100°C (212°F), with five minutes of recovery at 22°C (room temperature, ~72°F) between sets. The other half carried out normal activities for the duration of the study. The participants underwent bioelectrical impedance and dual-energy X-ray absorptiometry (DEXA) scans to gauge body composition prior to the first sauna session, at the completion of the last sauna session, and two weeks later.
None of the participants experienced any changes in fat mass during the study. However, the DEXA scans revealed that the men who engaged in the sauna sessions experienced increases in their muscle mass, bone mineral content, and bone mineral density, compared to the men who did not engage in sauna sessions.
These findings suggest that heat stress encountered during sauna use exerts favorable changes in lean body composition. Learn more about the health benefits of sauna use in this comprehensive review by Dr. Rhonda Patrick.
Link to full publication.
Vaccination against COVID-19 cuts risk of long-term complications following breakthrough infection by half.
The delta variant of SARS-CoV-2, the virus that causes COVID-19, exhibits greater resistance to antibodies and higher transmissibility than other variants, raising concerns that people who have been vaccinated might be vulnerable to breakthrough infections and subsequent complications. Findings from a recent study indicate that people who are vaccinated against COVID-19 are less likely to develop long-term complications following breakthrough infections.
COVID-19 is an acute illness caused by infection with the SARS-CoV-2 virus. Although most people recover from COVID-19 within a few weeks of presenting with symptoms, some experience long-term complications that affect multiple organs, including the heart, lung, kidney, skin, and brain.
The prospective, case-control study drew on self-reported data from more than 1 million United Kingdom-based adult users of the COVID Symptom Study mobile phone app. Participants had received at least one dose of the two-dose AstraZeneca, Moderna, or Pfizer vaccines during an eight-month period between December 2020 and July 2021. The authors of the study matched vaccinated persons who tested positive for COVID-19 (cases) with vaccinated persons who tested negative for COVID-19 (controls). They also included data from unvaccinated persons.
Of the 1.2 million people who had received only one dose, approximately 0.5 percent reported a breakthrough infection. Of the nearly 1 million people who had received both doses, approximately 0.2 percent reported a breakthrough infection. Those who experienced breakthrough infections were 49 percent less likely to experience long-term complications, were less likely to be hospitalized, and were more likely to have few or no symptoms than unvaccinated persons. People who lived in low-income areas or had obesity were more likely to experience breakthrough infections after receiving only one dose.
These findings suggest that vaccination against COVID-19 reduces the risk of long-term complications following breakthrough infections by half. They underscore the importance of continued efforts to vaccinate eligible persons, especially those who are more likely to experience long-term complications, such as those who live in low-income areas or who have obesity. Learn more about the long-term complications of COVID-19 in this clip featuring Dr. Roger Seheult.
Link to full publication.
Eating walnuts lowers LDL cholesterol.
Heart disease is the leading cause of death among people living in the United States, claiming the lives of roughly 655,000 people every year. Having high levels of low-density lipoprotein (LDL), or “bad” cholesterol, increases a person’s risk of heart disease. Findings from a new study suggest that eating walnuts reduces LDL cholesterol.
Walnuts contain a variety of bioactive compounds that exert antioxidant, anti-inflammatory, and anti-cancer properties. They are also excellent sources of alpha linolenic acid (ALA), an omega-3 fatty acid that plays important roles in human health. ALA is necessary for the production of eicosanoids, a class of signaling molecule that regulates blood clotting, blood pressure, blood lipid levels, immune function, inflammation, pain and fever, and reproduction.
The investigation was part of the Walnuts and Healthy Aging study, an intervention study of health and cognition in approximately 700 healthy older adults (63 to 79 years old) recruited from diverse geographical locations in the United States and Spain. Over a period of two years, half of the participants in each location followed their normal diets but added one serving (about 1/2 cup, a small handful) of walnuts to their diet per day. The other half followed their normal diets but did not add walnuts.
The study investigators measured the participants’ triglycerides, total cholesterol, LDL, and high-density lipoprotein (HDL) blood concentrations at the beginning and end of the intervention. They also measured intermediate-density lipoproteins (IDL) and LDL particle number. IDL is a precursor to LDL. In recent years it has emerged as an important cardiovascular risk factor independent of LDL cholesterol. LDL particle number is a measure of small LDL particles in a person’s blood. Evidence suggests small LDL particles are more atherogenic than large ones.
The effects of adding walnuts to the diet were consistent across both geographical locations. Among those who ate walnuts, total cholesterol concentrations decreased by 4.4 percent, LDL decreased by 3.6 percent, and IDL decreased by 16.8 percent. Triglycerides and HDL cholesterol concentrations did not change. Total LDL particles decreased by 4.3 percent, and small LDL particle number decreased by 6.1 percent. Interestingly, the LDL-lowering effects of the walnut diet differed by sex, with a 7.9 percent decrease in LDL among men and a 2.6 percent decrease among women.
These findings suggest that walnuts exert potent lipid-lowering effects in healthy older adults and align with previous research demonstrating that foods rich in omega-3 fatty acids benefit cardiovascular health.
Link to full publication.
Learn more about the heart-protective effects of omega-3 fatty acids in this short video featuring Dr. Rhonda Patrick.
Folate reduces risk for Alzheimer’s disease.
Alzheimer’s disease, the most common type of neurodegenerative disease in older adults, causes a progressive deterioration of cognitive function. Recent research indicates that deficiencies in certain micronutrients, such as vitamin A and folate, may play roles in Alzheimer’s disease pathology. A recent systematic review and meta-analysis reports that folate deficiency increases the risk for Alzheimer’s disease.
Folate is an essential nutrient used by the body to create new DNA and RNA and to metabolize amino acids, all of which are necessary for cell division. Good sources of folate include legumes, such as peanuts and chickpeas, and green vegetables, such as spinach and asparagus. Previous research has shown that folate supplementation improves cognitive function in older adults through mechanisms that are not well-understood, but likely involve reduced inflammation.
Because dose, population characteristics, and testing methods often vary among clinical trials, coming to a consensus about the efficacy of an investigational treatment presents challenges. However, review articles can be a valuable way to combine and report existing data in a new and informative way. This study is a systematic review and meta-analysis, meaning that the authors searched existing literature for studies related to folate and Alzherimer’s disease, collected studies based on a set of criteria meant to select for high-quality design, and then combined the data and reanalyzed it.
The authors selected 59 studies that met their criteria for high-quality design. In a sample of more than 2,000 participants from a collection of case-control studies, participants with folate deficiency (less than 13.5 nanomoles per liter) were more than twice as likely to develop Alzheimer’s disease compared to participants with normal folate status (greater than 13.5 nanomoles per liter). Likewise, data from a collection of five cohort studies revealed that participants with folate deficiency were 88 percent more likely to develop Alzheimer’s disease compared to those with sufficient folate status. Finally, in a sample of 11 cohort studies, participants who consumed less than the recommended dietary allowance (400 micrograms) were 70 percent more likely to develop Alzheimer’s disease than those who consumed 400 micrograms or more of folate per day.
This review of the evidence supports a relationship between folate intake and serum folate concentration in reducing risk for developing Alzheimer’s disease. Future studies should utilize an interventional design to investigate the mechanisms of folate in Alzheimer’s pathology.
Link to full publication.
Learn how zinc deficiency may also contribute to Alzheimer’s disease risk in this clip featuring Dr. Dale Bredesen.
Many people infected with SARS-CoV-2 do not develop antibodies to the virus.
Current vaccines against COVID-19 provide powerful protection against the disease. Some evidence suggests that when people who have been infected with the original strain of SARS-CoV-2 (the virus that causes COVID-19) are vaccinated against the disease, they develop unusually robust immunity, a phenomenon known as “hybrid immunity.” However, a recent report describes findings that suggest many people infected with SARS-CoV-2 do not develop antibodies to the virus.
The study involved 72 people who had tested positive for COVID-19 but were symptom-free for at least three weeks. The authors of the study tested the participants’ blood for the presence of antibodies to the spike protein (the primary infectious particle of the SARS-CoV-2 virus) as well as other viral particles at the time of enrollment and at subsequent follow-up visits. They gathered information regarding the participants’ demographics, viral load, and symptom severity.
Two of the participants (3 percent) reported no symptoms, 13 (18 percent) reported mild symptoms, 48 (67 percent) reported moderate symptoms, and 9 (12 percent) reported severe symptoms. The authors’ analysis revealed that 36 percent of the participants failed to develop detectable antibody levels against the SARS-CoV-2 spike protein or other infectious particles. Those who did not develop antibodies were on average 10 years younger and had lower viral loads than those who developed higher antibody levels.
These findings indicate that the antibody response to SARS-CoV-2 infection is variable and subject to a variety of factors. Vaccines against COVID-19, on the other hand, provide predictable antibody responses in vaccinated persons. It is important to note that although antibodies are important components of the body’s immune response, cellular immunity plays a critical role, too. Learn more about COVID-19 vaccines in this clip featuring Dr. Roger Seheult.
Link to full publication.
Whole-body hyperthermia activates muscle hormone irisin and increases neuroprotective factors.
Exposure to high heat while sauna bathing causes mild hyperthermia – an increase in the body’s core temperature – that induces a thermoregulatory response to restore homeostasis and condition the body for future heat stressors. These adaptations to high temperatures involve increased production of brain derived neurotrophic factor (BDNF), a promoter of neuroplasticity, and irisin, a biomarker of exercise. Findings of a new report demonstrate that whole-body hyperthermia increases BDNF and irisin in healthy young adults.
Whole-body hyperthermia is a therapeutic strategy used to treat various diseases, including cancer and depression. Previous research has shown that use of a hyperthermia chamber increases BDNF to a greater extent than light intensity exercise. Some research has suggested that BDNF production is stimulated by irisin, a hormone secreted from muscle in response to exercise. Irisin may mediate some of the beneficial effects of exercise and sauna use in humans, but additional research is needed to confirm these findings.
The authors recruited 20 male participants (average age, 22 years) and assessed their baseline heat tolerance using a hyperthermia protocol. Participants reclined in a hyperthermia chamber while the researchers increased the temperature of the chamber by 50°F every ten minutes until the participant reached their personal heat threshold. Next, participants completed ten hyperthermia sessions tailored to their baseline conditioning, during which the hyperthermia chamber was set to a temperature of 150° to 175°F. Following a three-week wash-out period, they completed ten sham treatments over two weeks, during which the hyperthermia chamber was set to a temperature of 75° to 77°F.
Participants had an average core body temperature of 102°F at the end of each whole-body hyperthermia treatment. Following ten whole-body hyperthermia treatments, participants had a significant increase in circulating irisin levels (6.3 micrograms per milliliter) compared to their baseline levels (5.0 micrograms per milliliter) and compared to their irisin levels following the sham treatment (5.4 micrograms per milliliter). Whole-body hyperthermia treatment also significantly increased BDNF levels (28.3 picograms per liter) compared to baseline (25.9 picograms per liter).
These findings indicate that in healthy young adults, whole-body hyperthermia significantly increases irisin and BDNF levels. The authors noted that future studies should explore the effects of whole-body hyperthermia on adipose tissue, which also produces irisin.
Link to full publication.
Learn more about the connections between whole-body hyperthermia, BDNF, and brain health in our overview article.
Omega-3 fatty acids slow memory loss in people with Alzheimer’s disease.
Omega-3 fatty acids are essential for human health. They participate in pathways involved in the biosynthesis of hormones that regulate blood clotting, contraction and relaxation of artery walls, and inflammation. They have been shown to help prevent heart disease and stroke; may help control lupus, eczema, and rheumatoid arthritis; and may play protective roles in cancer and other conditions. Findings from a new study suggest that omega-3 fatty acids slow cognitive decline in Alzheimer’s disease.
Alzheimer’s disease is a neurodegenerative disorder characterized by progressive memory loss and cognitive decline. The primary risk factor for Alzheimer’s disease is aging, with risk roughly doubling every five years after the age of 65 years. Nutritional status also plays key roles in Alzheimer’s disease risk and pathology.
The intervention study involved 33 people who had been diagnosed with Alzheimer’s disease. Approximately half of the participants took a supplement providing 2.3 grams of omega-3 fatty acids daily for six months; the other half took a placebo. All participants took the Mini Mental State Examination (MMSE), a widely accepted measure of memory and cognitive function, before and after the intervention. The study investigators collected cerebrospinal fluid samples before and after the intervention to measure several biomarkers associated with neurodegenerative diseases and inflammation, including amyloid beta proteins, tau, interleukin 6, chitinase-3-like protein 1 (YKL-40), and neurofilament light (NfL). YKL-40 is associated with neuroinflammation, and NfL is associated with damage to the axons of nerves in brain white matter.
The MMSE scores of the participants who took the omega-3 fatty acid supplements remained stable over the six-month intervention, decreasing by only 0.06 points, but the scores of those who took the placebo decreased by 2.0 points. The two groups’ biomarkers were similar at the beginning of the intervention, but YKL-40 and NfL increased slightly in the group that received the omega-3 fatty acid supplement, indicating a possible increase in neurodegeneration and inflammatory responses. However, the increase in the two biomarkers did not correlate with the participants’ MMSE scores.
These findings suggest that omega-3 fatty acids help maintain memory and cognitive function in older adults with Alzheimer’s disease. This was a very small study, however, and further research is needed to confirm any protective effects of omega-3 fatty acid intake in Alzheimer’s disease.
Link to study abstract.
Learn more about the links between DHA (a type of omega-3 fatty acid) and Alzheimer’s disease in this perspective by Dr. Rhonda Patrick.
mRNA vaccines provide long-lasting immunity and protection from SARS-CoV-2 variants.
SARS-CoV-2 mRNA vaccines (e.g., Moderna and Pfizer-N-BioTech) are effective at preventing infection as well as preventing severe COVID-19 illness and hospitalization. However, many people in the United States received their vaccine early in 2021, more than six months before the time of this writing. Whether the protection afforded by vaccination lasts as time passes and more SARS-CoV-2 variants emerge is unclear. Findings of a report published in August 2021 provide insights into long-term immunity following vaccination or SARS-CoV-2 infection, concerns about emerging variants, and implications for vaccination boosters.
During infection with a virus, the innate immune system immediately launches an inflammatory response to fight the infection. Within days or weeks, the adaptive immune system produces antibodies that are specific to the virus. These antibodies bind to a small piece of the viral particle, called an antigen. White blood cells such as macrophages and neutrophils participate in the innate response, while B and T cells facilitate the adaptive response. Plasma B cells are responsible for producing antibodies; however, these cells steadily decrease in number over time. Memory B cells store the genetic information needed to produce virus-specific antibodies upon reinfection. Memory T cells are also responsible for “remembering” viruses in this way. Memory CD4+ T cells rapidly respond to reinfection to support inflammation and antibody production. Memory CD8+ T cells, also called cytotoxic T cells, bind to virus-infected host cells and order them to undergo apoptosis (i.e., programmed cell death).
The authors of the report analyzed 342 blood samples collected from 61 participants at one, three, and six months following vaccination. This group of participants included SARS-CoV-2 naive individuals (i.e., those who were never infected with the virus) and SARS-CoV-2 recovered individuals. The investigators measured the concentration of circulating antibodies that bind to the SARS-CoV-2 receptor binding domain protein and spike protein. They also measured the concentration of memory B cells and T cells and characterized these cells’ response when challenged with SARS-CoV-2 antigens.
The concentration of serum antibodies in the participants’ blood declined over time, but was still detectable at six months post-vaccination. mRNA vaccination produced memory B cells that respond to the receptor binding domain protein of the Alpha, Beta, and Delta variants, a phenomenon called cross-binding memory. These memory B cells had significantly more hypermutation, the process by which B cells rearrange their DNA in order to produce antibodies to new antigens, and increased in concentration between three and six months post-vaccination. Cross-binding B cells were more common in SARS-CoV-2 recovered participants than naive participants. mRNA vaccination also increased memory CD4+ and CD8+ T cells.
The immune response to mRNA vaccination and infection with the SARS-CoV-2 virus evolves over time, which may have implications for the future use of booster vaccines. These results should be considered with caution as this research has yet to be peer-reviewed.
Link to full publication.
Learn more about how mRNA vaccines work in this clip featuring pulmonologist Dr. Roger Sehuelt and Dr. Rhonda Patrick.
Muscles contain sensors for mechanical force that drive growth following exercise.
The question of why muscles grow after exercise seems to have a simple answer – they grow by repairing themselves from the damage exercise causes. However, this theory does not explain the loss of muscle mass that occurs after long periods of rest or in microgravity environments, such as those encountered in space. Authors of a new report suggest that muscle growth is regulated by structures within muscle cells that sense changes in mechanical force.
Muscle fibers lengthen and shorten in cycles to create muscle movement. Fast muscle fiber cycling is use during the fight or flight response, generating nearly instantaneous motion. Over periods of several days, muscles regulate their growth based on the number of these contraction cycles. But how muscles “know” how much they have been used has yet to be elucidated.
The sarcomere is the smallest structural unit of striated muscle (i.e., skeletal and cardiac muscle) and is composed of thin actin and thick myosin filaments, which slide against each other to create the force needed for contraction and relaxation. Titin is a protein at the core of the myosin filaments that changes shape when force is applied. Force “opens” the titin protein structure, exposing a molecular site for phosphorylation (i.e., adding a phosphate group). This phosphorylation initiates a signaling cascade that results in changes to gene expression that affect long-term growth or atrophy of skeletal muscles.
The authors created a mathematical model to explain the mechanism of the mechanosensing (force-sensing) function of titin. The model was divided into three parts. The first part of the model characterized the opening of the titin protein structure in response to force. The second part of the model characterized the creation and degradation of signaling molecules that are downstream in the signaling cascade initiated by titin phosphorylation. The third part of the model characterized how muscle cells compensate for the depletion of short-term adenosine triphosphate (ATP) energy stores that results from energy production through oxidative phosphorylation.
From the modeling calculations, the authors found that titin acts as a mechanosensitive switch that is put under extreme force during resistance exercise (e.g., weight lifting) and less force during endurance exercise (e.g., jogging). The model also explained that titin phosphorylation geometrically inhibits the function of ribosomes, the cell structures that build proteins. Following exercise, some protein synthesis in the muscle is inhibited; however, after a lag of days or weeks, repeated exercise increases the rate of ribosome gene expression and synthesis. Building on this information, the model yielded that these alterations in protein synthesis are ultimately responsible for muscle hypertrophy (growth) following exercise and muscle atrophy following extended rest.
The authors noted that this important research may identify targets for future therapies that prevent the loss of muscle mass that occurs with age and with diseases such as cancer and HIV.
Link to full publication.
