A method of lowering brain tryptophan and, thus, serotonin (5-HT). Administration of a bolus, usually a drink, containing large neutral amino acids (LNAA), but lacking tryptophan, limits the transport of endogenous tryptophan across the blood-brain barrier through competition with other LNAAs undergoing active transport. This is able to subsequently decrease serotonergic neurotransmission and is a useful way for scientists to study the effects of this type of neurotransmission.

The primary protein present in human blood plasma. Albumin binds water, minerals, fatty acids, hormones, bilirubin, and many drugs. Its main function is to regulate the oncotic pressure of blood, a form of osmotic pressure exerted by proteins that tends to pull water into the circulatory system.

A molecule that inhibits oxidative damage to DNA, proteins, and lipids in cells. Oxidative damage plays a role in the aging process, cancer, and neurodegeneration. Many vitamins and plant-based compounds are antioxidants.

Programmed cell death. Apoptosis is a type of cellular self-destruct mechanism that rids the body of damaged or aged cells. Unlike necrosis, a process in which cells that die as a result of acute injury swell and burst, spilling their contents over their neighbors and causing a potentially damaging inflammatory response, a cell that undergoes apoptosis dies in a neat and orderly fashion – shrinking and condensing, without damaging its neighbors. The process of apoptosis is often blocked or impaired in cancer cells. (May be pronounced “AY-pop-TOE-sis” OR “AP-oh-TOE-sis”.)

A developmental disorder characterized by impaired social interaction, behavioral problems, and poor communication. Autism typically manifests in early childhood and is slightly more common among boys than girls. In clinical trials, sulforaphane, a compound derived from broccoli and broccoli sprouts, reduces the characteristic behaviors associated with autism.

A division of the peripheral nervous system that influences the function of internal organs. The autonomic nervous system regulates bodily functions that occur below the level of consciousness, such as heart rate, digestion, respiratory rate, pupillary response, urination, and sexual arousal. It is the primary mechanism in control of the fight-or-flight response and the freeze-and-dissociate response.

A hormone produced in the brain that blocks the sensation of pain. Beta-endorphin is released in response to a wide range of painful stimuli and stressors, including heat.^[1] Beta-endorphin exhibits morphine-like activity, but its effects are up to 33-times more potent than morphine.^[2] Both morphine and beta-endorphin act on the μ-opioid receptor.

A member of the same species.

A steroid hormone that participates in the body’s stress response. Cortisol is a glucocorticoid hormone produced in humans by the adrenal gland. It is released in response to stress and low blood glucose. Chronic elevated cortisol is associated with accelerated aging. It may damage the hippocampus and impair hippocampus-dependent learning and memory in humans.

A broad category of small proteins (~5-20 kDa) that are important in cell signaling. Cytokines are short-lived proteins that are released by cells to regulate the function of other cells. Sources of cytokines include macrophages, B lymphocytes, mast cells, endothelial cells, fibroblasts, and various stromal cells. Types of cytokines include chemokines, interferons, interleukins, lymphokines, and tumor necrosis factor.

A group of interacting brain regions implicated in self-related thinking, rumination, and depression. The default mode network is typically active when a person is not focused on the outside world and the brain is at wakeful rest, such as during daydreaming and mind-wandering. Functions include autobiographical information, self-reference, emotions of one's self and others, theory of mind, moral reasoning, social evaluations, social categories, remembering past, imagining future, and story comprehension.

A general term referring to cognitive decline that interferes with normal daily living. Dementia commonly occurs in older age and is characterized by progressive loss of memory, executive function, and reasoning. Approximately 70 percent of all dementia cases are due to Alzheimer’s disease.

A mood disorder characterized by profound sadness, fatigue, altered sleep and appetite, as well as feelings of guilt or low self-worth. Depression is often accompanied by perturbations in metabolic, hormonal, and immune function. A critical element in the pathophysiology of depression is inflammation. As a result, elevated biomarkers of inflammation, including the proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, are commonly observed in depressed people. Although selective serotonin reuptake inhibitors and cognitive behavioral therapy typically form the first line of treatment for people who have depression, several non-pharmacological adjunct therapies have demonstrated effectiveness in modulating depressive symptoms, including exercise, dietary modification (especially interventions that capitalize on circadian rhythms), meditation, sauna use, and light therapy, among others.

Animals characterized by higher activity during the day and sleeping more at night.

A neurotransmitter best known for its role in motor, motivation, and pleasure control. Dopamine also functions as a paracrine (cell-to-cell) hormone in other parts of the body. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Some evidence suggests that dopamine may also be involved in pain modulation.

A potent endogenous opioid peptide. Dynorphin acts on the kappa-opioid receptor and is associated with a transient feeling of dysphoria. It has many different physiological actions, depending upon its site of production, and is involved in addiction, temperature regulation, appetite, circadian rhythm, pain, stress, and depression. Dynorphin may also be involved in the body’s thermoregulatory response to hyperthermia.^[1]

The annual rites performed by the ancient Greeks at the village of Eleusis near Athens in honor of Demeter and Persephone. They've been referred to as "the most famous of the secret religious rites of ancient Greece" by the Encyclopedia Britannica. The rites, ceremonies, and beliefs were kept secret and consistently preserved from antiquity.

The tendency of things to change into their opposites, especially as a supposed governing principle of natural cycles and of psychological development.

A type of toxin released when bacteria die. Endotoxins can leak through the intestinal wall and pass directly into the bloodstream. The most common endotoxin is lipopolysaccharide (LPS), a major component of the cell membrane of gram-negative bacteria. If LPS leaks into the bloodstream, it can trigger an acute inflammatory reaction. LPS has been linked with a number of chronic diseases, including Alzheimer’s disease, inflammatory bowel disease (Crohn’s disease or ulcerative colitis), cardiovascular disease, diabetes, obesity, autoimmune disorders (celiac disease, multiple sclerosis, and type 1 diabetes), and psychiatric disorders (anxiety and depression).

Any of a group of complex proteins or conjugated proteins that are produced by living cells and act as catalyst in specific biochemical reactions.

A type of water-soluble B-vitamin, also called vitamin B9. Folate is critical in the metabolism of nucleic acid precursors and several amino acids, as well as in methylation reactions. Severe deficiency in folate can cause megaloblastic anemia, which causes fatigue, weakness, and shortness of breath. Certain genetic variations in folate metabolism, particularly those found in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene influences folate status. Inadequate folate status during early pregnancy increases the risk of certain birth defects called neural tube defects, or NTDs, such as spina bifida, anencephaly, and other similar conditions. Folate deficiency and elevated concentrations of homocysteine in the blood are associated with increased risk of cardiovascular disease. Low folate status and/or high homocysteine concentrations are associated with cognitive dysfunction in aging (from mild impairments to dementia). The synthetic form of folate is called folic acid. Sources of folate include most fruits and vegetables, especially green leafy vegetables.

The process in which information stored in DNA is converted into instructions for making proteins or other molecules. Gene expression is highly regulated. It allows a cell to respond to factors in its environment and involves two processes: transcription and translation. Gene expression can be turned on or off, or it can simply be increased or decreased.

A family of proteins produced by cells in response to exposure to stressful conditions. Heat shock proteins are expressed in response to heat as well as exposure to cold and UV light, and during wound healing and tissue remodeling. Many heat shock proteins function as chaperones by stabilizing new proteins to ensure correct folding or by helping to refold proteins that were damaged by cell stress. A 30-minute 73ºC sauna session in healthy young adults has been shown to cause a robust and sustained increase in the production of heat shock proteins for up to 48 hours afterward.^[1]

Relating to or characterized by pleasure. Hedonism is a school of thought that argues that pleasure and happiness are the primary or most important intrinsic goods and the aim of human life.

A small organ located within the brain's medial temporal lobe. The hippocampus is associated primarily with memory (in particular, the consolidation of short-term memories to long-term memories), learning, and spatial navigation. Amyloid-beta plaque accumulation, tau tangle formation, and subsequent atrophy in the hippocampus are early indicators of Alzheimer’s disease.

An organism’s ability to maintain its internal environment within defined limits that allow it to survive. Homeostasis involves self-regulating processes that return critical bodily systems to a particular “set point” within a narrow range of operation, consistent with the organism’s survival.

Biological responses to low-dose exposures to toxins or other stressors such as exercise, heat, cold, fasting, and xenohormetics. Hormetic responses are generally favorable and elicit a wide array of protective mechanisms. Examples of xenohormetic substances include plant polyphenols – molecules that plants produce in response to stress. Some evidence suggests plant polyphenols may have longevity-conferring effects when consumed in the diet.

The infection specificity of certain pathogens to particular hosts and host tissues. This type of tropism explains why most pathogens are only capable of infecting a limited range of host organisms. Pathogens that can infect a wide range of hosts and tissues are said to be amphotropic, while ecotropic pathogens, on the other hand, are only capable of infecting a narrow range of hosts and host tissue.

Hypothermia is a medical emergency that occurs when your body loses heat faster than it can produce heat, causing a dangerously low body temperature. Normal body temperature is around 98.6 F (37 C). Hypothermia occurs as your body temperature passes below 95 F (35 C)

A component of the innate immune system. The inflammasome is expressed in the myeloid cells and promotes the maturation of the pro-inflammatory cytokines IL-1B and IL-18. It is responsible for activation of inflammatory processes.

A critical element of the body’s immune response. Inflammation occurs when the body is exposed to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective response that involves immune cells, cell-signaling proteins, and pro-inflammatory factors. Acute inflammation occurs after minor injuries or infections and is characterized by local redness, swelling, or fever. Chronic inflammation occurs on the cellular level in response to toxins or other stressors and is often “invisible.” It plays a key role in the development of many chronic diseases, including cancer, cardiovascular disease, and diabetes.

A peptide hormone secreted by the beta cells of the pancreatic islets cells. Insulin maintains normal blood glucose levels by facilitating the uptake of glucose into cells; regulating carbohydrate, lipid, and protein metabolism; and promoting cell division and growth. Insulin resistance, a characteristic of type 2 diabetes, is a condition in which normal insulin levels do not produce a biological response, which can lead to high blood glucose levels.

(of two or more things) interlock like the fingers of two clasped hands.

A group of signaling proteins made and released by host cells in response to the presence of several pathogens, such as viruses, bacteria, parasites, and tumor cells. Interferons are named for their ability to interfere with viral replication and are critical components of the body's innate immune response to viruses. SARS-CoV-2, the virus that causes COVID-19, impairs the body's interferon response.

IL-10, also known as human cytokine synthesis inhibitory factor (CSIF), is an anti-inflammatory cytokine with multiple, pleiotropic, effects in immunoregulation and inflammation. It downregulates the expression of Th1 cytokines, MHC class II antigens, and co-stimulatory molecules on macrophages. It also enhances B cell survival, proliferation, and antibody production. A study in mice has shown that IL-10 is also produced by mast cells, counteracting the inflammatory effect that these cells have at the site of an allergic reaction. IL-10 is capable of inhibiting synthesis of pro-inflammatory cytokines such as IFN-γ, IL-2, IL-3, TNFα and GM-CSF made by cells such as macrophages and Th1 T cells.

A pro-inflammatory cytokine that plays an important role as a mediator of fever and the acute-phase response. IL-6 is rapidly induced in the context of infection, autoimmunity, or cancer and is produced by almost all stromal and immune cells. Many central homeostatic processes and immunological processes are influenced by IL-6, including the acute-phase response, glucose metabolism, hematopoiesis, regulation of the neuroendocrine system, hyperthermia, fatigue, and loss of appetite. IL-6 also plays a role as an anti-inflammatory cytokine through inhibition of TNF-alpha and IL-1 and activation of IL-1ra and IL-10.

The kaihōgyō (回峰行) ("circling the mountain") is an ascetic practice performed by Tendai Buddhist monks. The practice involves walking a route on Mount Hiei (the location of the Tendai school headquarters) while offering prayers at halls, shrines and other sacred places. There are two versions: • 100 days (hyaku-nichi kaihōgyō) • 1,000 days (sennichi kaihōgyō)

A compound produced during the conversion of the amino acid tryptophan to the vitamin niacin (vitamin B3). Kynurenine is pivotal to the tryptophan metabolism pathway because it can change into the neuroprotective agent kynurenic acid or to the neurotoxic agent quinolinic acid, the latter of which has been implicated in many disorders such as stroke, epilepsy, and multiple sclerosis, and in neurodegenerative disorders such as Parkinson's disease, Huntington's, and Alzheimer's disease.

Otherwise known as intestinal permeability – a condition in which gaps form between the tight junctions of the endothelial cells that line the gut. These gaps allow pathogens like bacteria or endotoxins – toxins that are released when bacteria die – to leak through the intestinal wall and pass directly into the bloodstream. The most common endotoxin is lipopolysaccharide (LPS), a major component of the cell membrane of gram-negative bacteria. If LPS leaks into the bloodstream, it can trigger an acute inflammatory reaction. LPS has been linked with a number of chronic diseases, including Alzheimer’s disease and cardiovascular disease.

A type of white blood cell. Macrophages engulf and digest cellular debris, foreign substances, microbes, cancer cells, and oxidized LDL in a process called phagocytosis. After phagocytizing oxidized LDL, macrophages are referred to as foam cells.

A hormone that regulates the sleep-wake cycle in mammals. Melatonin is produced in the pineal gland of the brain and is involved in the expression of more than 500 genes. The greatest influence on melatonin secretion is light: Generally, melatonin levels are low during the day and high during the night. Interestingly, melatonin levels are elevated in blind people, potentially contributing to their decreased cancer risk.^[1]

A cluster of at least three of five of the following medical conditions: abdominal (central) obesity, elevated blood pressure, elevated fasting plasma glucose, high serum triglycerides, and low high-density lipoprotein (HDL) levels. Some studies estimate the prevalence in the USA to be 34 percent of the adult population. Metabolic syndrome is associated with the risk of developing cardiovascular disease and diabetes.

The collection of genomes of the microorganisms in a given niche. The human microbiome plays key roles in development, immunity, and nutrition. Microbiome dysfunction is associated with the pathology of several conditions, including obesity, depression, and autoimmune disorders such as type 1 diabetes, rheumatoid arthritis, muscular dystrophy, multiple sclerosis, and fibromyalgia.

The term "mindfulness" is derived from the Pali-term sati which is an essential element of Buddhist practice, including vipassana, satipatthana and anapanasati. It has been popularized in the West by Jon Kabat-zinn with his mindfulness-based stress reduction (MBSR) program. Large population-based research studies have indicated that the construct of mindfulness is strongly correlated with well-being and perceived health.

Cytokines and other small proteins, including brain-derived neurotrophic factor (BDNF) and various interleukins, such as IL-6, which are produced and released by muscle cells in response to muscular contractions. Myokines have autocrine, paracrine and/or endocrine effects and are involved in exercise-associated metabolic changes and adaptations and also participate in tissue regeneration and repair, maintenance of healthy bodily functioning, immunomodulation, cell signaling, expression, and differentiation.

A catabolic product of GTP (the purine nucleotide) synthesized by human macrophages upon stimulation with interferon-gamma. High neopterin production is associated with increased production of reactive oxygen species and serves as an estimate of the extent of oxidative stress elicited by the immune system.

In general, anything that can produce disease. Typically, the term is used to describe an infectious agent such as a virus, bacterium, prion, fungus, or other microorganism.

Shared characteristics between different organisms due to similar ancestry

A disease state in which the hematocrit (the volume percentage of red blood cells in the blood) is elevated. It can be due to an increase in the number of red blood cells ("absolute polycythemia") or to a decrease in the volume of plasma ("relative polycythemia").

Relating to the period after eating. Postprandial biomarkers are indicators of metabolic function. For example, postprandial hyperglycemia is an early sign of abnormal glucose homeostasis associated with type 2 diabetes and is markedly high in people with poorly controlled diabetes.

Organisms that, although not reproducing and residing permanently in the gut, maintain a persistent presence through continual re-introduction via our environment, including through the food we eat and the water we drink.

A naturally occurring psychedelic compound produced by more than 200 species of mushrooms. As a prodrug, psilocybin is quickly converted by the body to psilocin, which has mind-altering effects including euphoria, visual and mental hallucinations, changes in perception, a distorted sense of time, and spiritual experiences, and can include possible adverse reactions such as nausea and panic attacks.

A class of hallucinogenic substances whose primary action is to alter cognition and perception, typically as serotonin receptor agonists, causing thought and visual/auditory changes, and "heightened state of consciousness." Major psychedelic drugs include mescaline, LSD, psilocybin, and DMT. Psychedelics have a long history of traditional use in medicine and religion, for their perceived ability to promote physical and mental healing.

A compound produced during the metabolism of the amino acid, tryptophan. Quinolinic acid is a neurotoxin released by activated macrophages. It may play roles in inflammation and neurodegenerative disorders. Elevated quinolinic acid levels are correlated with the severity of neuropsychological deficits in people who have AIDS.

The practice of dwelling on external stressors to excess. Rumination can set in motion a cascade of hormonal and physiological responses that harm mental and physical health. A key player in the body’s response to rumination is a biological pathway that starts in the brain’s hypothalamus with the release of corticotrophin-releasing hormone and has a direct effect on many parts of the body including the brain, gut, and DNA. Meditation has been shown to reduce rumination and its negative effects.

Salvinorin A is the main active psychotropic molecule in Salvia divinorum, a Mexican plant which has a long history of use as an entheogen by indigenous Mazatec shamans. Salvinorin A can produce psychoactive experiences in humans with a typical duration of action being several minutes to an hour or so. It is structurally distinct from other naturally occurring hallucinogens, acting on the k-opioid receptor instead of the 5-HT2A (serotonin) receptor.

A mental disorder characterized by abnormal social behavior and failure to understand what is real. Common symptoms include false beliefs, unclear or confused thinking, hearing voices that others do not, reduced social engagement and emotional expression, and a lack of motivation. People with schizophrenia often have additional mental health problems such as anxiety disorders, major depressive illness, or substance use disorders.

A small molecule that functions as both a neurotransmitter and a hormone. Serotonin is produced in the brain and gut and facilitates the bidirectional communication between the two. It regulates many physiological functions, including sleep, appetite, mood, thermoregulation, and others. Many antidepressants are selective serotonin reuptake inhibitors (SSRIs), which work by preventing the reabsorption of serotonin, thereby increasing extracellular levels of the hormone.

A change in one nucleotide DNA sequence in a gene that may or may not alter the function of the gene. SNPs, commonly called "snips," can affect phenotype such as hair and eye color, but they can also affect a person's disease risk, absorption and metabolism of nutrients, and much more. SNPs differ from mutations in terms of their frequency within a population: SNPs are detectable in >1 percent of the population, while mutations are detectable in <1 percent.

The junction between one neuron and another or a gland or muscle cell. Synapses are critical elements in the transmission of nerve signals. Their formation is necessary for the establishment and maintenance of the brain’s neuronal network and the precision of its circuitry.

A type of sweat lodge which originated with pre-Hispanic Indigenous peoples in Mesoamerica. The word temazcal comes from the Nahuatl word temāzcalli ("house of heat"), or possibly from the Aztec teme (to bathe) and calli (house).

A physiological process that results in the production of heat. There are two types of thermogenesis: shivering and nonshivering. Shivering thermogenesis, as its name implies, involves shivering to produce heat. During shivering, skeletal muscles undergo repeated, rapid contractions that produce little net movement and instead, produce heat. Nonshivering thermogenesis generates heat in the absence of shivering by unique mechanisms in both skeletal muscle and adipose (fat) tissue depots. These processes involve uncoupling electron transport from ATP synthesis and repetitive, non-productive transport of ions across the adipose cell membrane.

A pathogen that has been shown to alter the behavior of infected rodents in ways that increase their chances of being preyed upon by felids. Support for this "manipulation hypothesis" stems from studies showing T. gondii-infected rats have a decreased aversion to cat urine. Because cats are the only hosts within which T. gondii can sexually reproduce to complete and begin its lifecycle (a "definitive host"), such behavioral manipulations are thought to be evolutionary adaptations that increase the parasite's reproductive success. Though humans and other mammals are not definitive hosts of T. gondii, infection is thought to be widespread with estimates in countries like France as high as 84%.

An essential amino acid. Tryptophan plays key roles in the biosynthesis of proteins and is a precursor to several molecules with physiological significance, including melatonin, niacin, and the neurotransmitter serotonin. Inflammation causes tryptophan to be reallocated from serotonin synthesis to that of kynurenine, which then converts to the neurotoxin quinolinic acid, leading to depression. Dietary sources of tryptophan include most protein-based foods, such as meat, beans, or nuts.

A potent water-soluble antioxidant found in citrus fruits. Vitamin C is an essential nutrient involved in tissue repair, neurotransmission, and immune system function. Also known as ascorbic acid.

The Yokuts (previously known as Mariposas) are an ethnic group of Native Americans native to central California. Before European contact, the Yokuts consisted of up to 60 tribes speaking the same language. "Yokuts" means "People."