Ray Cronise on Cold Thermogenesis, Intermittent Fasting, Weight Loss & Healthspan
Posted on May 4th 2016 (almost 2 years)
Dr. Rhonda Patrick speaks with Ray Cronise, a former NASA material scientist and co-founder of zero gravity, a company that offers weightless parabolic flights to consumers and researchers. In this episode, coming at the tail end of a rather extreme 23-day water fast for Ray, we discuss, perhaps unsurprisingly, some of the benefits that are associated with fasting! Ray talks about shifting one's perspective from looking at nutrition only through the lens of meeting day-to-day nutritional needs, and instead, also considering optimizing metabolism for longer-term effects as well, the importance of thinking about longevity in the context of functional healthspan, some of the similarities between the body’s physiological response to heat stress, cold stress, and exercise and so much more.
A nonessential amino acid that is able to be manufactured by the human body and not dietarily required. It is nevertheless found in a wide variety of foods, and is particularly concentrated in meats.
An intracellular degradation system that involves the self-destruction of a cell by degrading its cellular components. This process is used to generate energy and is one reason why fasting increases cellular autophagy to provide energy for surviving cells. Damaged cells are often cleared away via autophagy, and this mechanism is thought to help protect against cancer and even aging by reducing the burden of abnormal cells. **However, the relationship between autophagy and cancer is complex**: autophagy may prevent the survival of pre-malignant cells, but can also be hijacked as a malignant adaptation by cancer, providing it a useful means to scavenge resources needed for further growth.
A laboratory analysis performed on a blood sample obtained either from a needle or finger prick. Blood tests are often used in healthcare to determine disease, mineral content, pharmaceutical drug effectiveness, and organ function. Typical clinical blood panels include a basic metabolic panel or a complete blood count.
A bow wave is the wave that forms at the bow or "forward part" of a ship when it moves through the water. As the bow wave spreads out, it defines the outer limits of a ship's wake.
The belief that it is possible for a person to live without consuming food. Breatharians claim that food, and in some cases water, are not necessary for survival, and that humans can be sustained soley by prana, the vital life force in Hinduism.
Restricting caloric intake by 30% has been shown to extend lifespan in some animals.
Organic pigments that are found mainly in the chloroplasts of plants and are responsible for absorbing light. Plants use carotenoids to create energy and protection from harmful UV rays and animals commonly use carotenoids as a precursor for vitamin A.
A member of the molluscan class Cephalopoda. The class now contains two, only distantly related, extant subclasses: Coleoidea, which includes octopuses, squid, and cuttlefish; and Nautiloidea, represented by Nautilus and Allonautilus. In the Coleoidea, the molluscan shell has been internalized or is absent, whereas in the Nautiloidea, the external shell remains.
Recurring naturally on a twenty-four-hour cycle, even in the absence of light fluctuations. Every cell in the human body follows a circadian rhythm, which governs when a cell is most metabolically active, when hormones are produced, when repair processes are activated, and more.
A substance whose presence is essential for the activity of an enzyme. Many minerals and vitamins are cofactors for enzymes.
Complex carbohydrate foods provide vitamins, minerals, and fiber that are important to the health of an individual. As opposed to simple or refined sugars, which do not have the vitamins, minerals, and fiber found in complex and natural carbohydrates. Simple sugars are often called "empty calories" because they have little to no nutritional value.
A broad and loose category of small proteins (~5-20 kDa) that are important in cell signaling. They are released by cells and affect the behavior of other cells. Cytokines include chemokines, interferons, interleukins, lymphokines, and tumor necrosis factor. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B lymphocytes, and mast cells as well as endothelial cells, fibroblasts, and various stromal cells.
The process by which amino acids are broken down. The amino group is removed from the amino acid and converted to ammonia. The rest of the amino acid is made up of mostly carbon and hydrogen, and is recycled or oxidized for energy.
A medical condition in which patches of skin become rough and inflamed. with blisters that cause itching and bleeding, sometimes resulting from a reaction to irritation (eczematous dermatitis) but more typically having no obvious external cause.
Essential Amino Acids
Amino acids that cannot be synthesized from scratch by the organism, but must be supplied via diet. The nine amino acids humans cannot synthesize are phenylalanine, valine, threonine, tryptophan, methionine, leucine, isoleucine, lysine, and histidine.
A molecule composed of carboxylic acid with a long hydrocarbon chain, which is either saturated or unsaturated. Fatty acids are an important component of cell membranes and are key sources of fuel because, when metabolized, they yield large quantities of ATP. Many cell types can use either glucose or fatty acids for this purpose.
Transfer of fecal material contain bacteria and natural antibacterials from a healthy individual into a diseased recipient.
Fecundity is similar to fertility. Representative of an organism's potential to create offspring.
Flavonoid are widely distributed in plants, fulfilling many functions. Flavonoids have been shown to have a wide range of biological and pharmacological activities in animal, human, and in-vitro studies. Examples include anti-allergic, anti-inflammatory, antioxidant, antimicrobial, anti-cancer, and anti-diarrheal activities.
Also known as Vitamin B9. Folate serves as a precursor to the DNA nucleotide thymine. FOlate deficiency, consequently, has been associated with uracil substitutions, which can cause strand breaks in DNA. Folate is also used to create methyl groups, which are used in genetic regulation (epigenetics), as well as used to convert homocysteine into methionine. ~8% of people in the United States are deficient in folate.
A gene for which increases in activity have been associated with longevity. FOXO3 is a master regulator of many genes involved in dealing with stress, including DNA repair genes, protein misfolding genes, antioxidant genes, anti-inflammatory genes, etc. Humans with a more active version of this gene have a 2.7-fold increased chance of living to be a centenarian.
Refers to how active a gene is. Genes that are highly expressed are active and producing protein and genes that are not expressed are not active.
A metabolic pathway in which the liver produces glucose from non-carbohydrate substrates including glycogenic amino acids (from protein) and glycerol (from lipids).
A polysaccharide, molecularly similar to starch, constituting the principal carbohydrate store material in animals and occurring chiefly in the liver and muscle. Glycogen makes up 5 to 6% of the fresh weight of the liver, and around 1-2% of the muscle mass, the amount of which is affected by things like physical training, basal metabolic rate (BMR), and eating habits.
Gram negative Bacteria
Gram negative bacteria contain within their outer membrane lipopolysaccharides (LPS). This substance is known to elicit strong immune responses in animals and is also used experimentally to induce inflammation in the lab. These molecules are also referred to as **endotoxin** and bacteria that have been killed by the immune system in the gut are the major source of endotoxin.
Individual's basal metabolic rate (BMR) and daily kilocalorie requirements. The estimated BMR values is multiplied by a number that corresponds to the individual's activity level. The resulting number is the recommended daily kilocalorie intake to maintain current body weight.
The number of years a person is able to live in good health.
The production of red bloods cells, white blood cells, and platelets from hematopoietic stem cells, which occurs in the bone marrow. Also called hematogenesis, or hematopoiesis.
Hemoglobin A1C (Glycated Hemoglobin)
A biomarker for the three-month average plasma glucose concentration. It is formed in a non-enzymatic glycation pathway by the hemoglobin's exposure to plasma glucose. As the average amount of plasma glucose increases, the fraction of glycated hemoglobin increases in a predictable way. In diabetes mellitus, higher amounts of glycated hemoglobin, indicating poorer control of blood glucose levels, have been associated with cardiovascular disease, nephropathy, neuropathy, and retinopathy. _Also known as HbA1c_.
Warm-blooded animal species can maintain a body temperature higher than their environment. In particular, homeothermic species maintain a stable body temperature by regulating metabolic processes.
The term for generally-favorable biological responses to low exposures to toxins or other stressors such as exercise, heat stress, fasting, and **xenohormetics**, which are molecules, including plant polyphenols, which are produced in response to stress experienced by plants and can have a longevity-conferring effect in consumers of the plant. Compounds like polyphenols themselves similarly are beneficial, in part, because they trigger mild cellular stress that induces beneficial stress response pathways.
the process of growing plants in sand, gravel, or liquid, with added nutrients but without soil.
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)
Indirect calorimetry calculates heat that living organisms produce by measuring either their production of carbon dioxide and nitrogen waste, or from their consumption of oxygen. This can be combined with other experimental methods to investigate numerous aspects of nutrient assimilation, thermogenesis, the energetics of physical exercise, and the pathogenesis of metabolic diseases.
Part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective response that involves immune cells, blood vessels, and molecular mediators. Chronic inflammation is characterized by simultaneous destruction and healing of the tissue from the inflammatory process.
Insulin-like growth factor 1 (IGF-1)
One of the most potent natural activators of the AKT signaling pathway, stimulator of cell growth and proliferation, potent inhibitor of programmed cell death, primary mediator of the effects of growth hormone, and has been implicated in contributing to aging and enhancing the growth of cancer after it has been initiated. Similar in molecular structure to insulin, IGF-1 plays a role during childhood for growth and continues later in life to have anabolic, as well as neurotrophic effects. Protein intake increases IGF-1 levels in humans, independent of total caloric consumption.
A period of fasting between meals that can last several hours to days that increases the production of ketones due to the use of stored fat as an energy source. Intermittent fasting also activates some of the same genetic pathways as caloric restriction.
A protein secreted from muscle in response to exercise that may mediate some beneficial effects of exercise in humans. Role of irisin in generating weight loss and blocking diabetes has been suggested.
A playful imitation of language consisting of invented, meaningless words; nonsense; gibberish. This term was coined by Lewis Carroll in Jabberwocky, a poem in Through the Looking Glass (1871).
The Sami people. An indigenous Finno-Ugric people inhabiting the Arctic area of Sapmi, which today encompasses parts of far northern Norway, Sweden, Finland, the Kola Peninsula of Russia, and the border area between south and middle Sweden and Norway.
A hormone found in animals (and conserved in plants, fungi, and bacteria) that is critical in regulating our relationship with the light-dark circadian cycle down to a cellular level and also functions as an antioxidant. Melatonin regulates over 500 genes, and, interestingly, has been shown to be elevated in the blind and may play a part in their decreased cancer risk.  Feychting, Maria, Bill Österlund, and Anders Ahlbom. "Reduced cancer incidence among the blind."_ Epidemiology_ (1998): 490-494.
The thousands of biochemical processes that run all of the various cellular processes that produce energy. Since energy generation is so fundamental to all other processes, in some cases the word metabolism may refer more broadly to the sum of all chemical reactions in the cell.
A sulfur-containing amino acid that is a constituent of most proteins. It is an essential nutrient in the diet of vertebrates. Methionine restriction in lower organisms has been shown to extend lifespan.
The trillions of microorganisms that live on or in the body. Microbiomes exist all throughout the body including skin, mouth, intestines, gut, and hair. There is some evidence that certain population level gut signatures may have a strong correlative and even causative relationship with health status, including obesity.
Vitamins and minerals that are required by organisms throughout life in small quantities to orchestrate a range of physiological functions. The term micronutrients encompasses vitamins, minerals, essential amino acids, essential fatty acids.
Nicotinamide adenine dinucleotide (NAD) is a coenzyme found in all living cells used to transfer chemical energy from a food source to the electron transport chain. It exists in two forms, an oxidized and reduced form abbreviated as NAD+ and NADH respectively. NAD levels rise during a fasting state and activates the SIRT1 pathway. NADH levels rise during the fed state and serve as reducing equivalents to produce ATP.
The hormone and neurotransmitter most responsible for vigilant concentration. Its role as a neurotransmitter has been exploited as a molecular target for a class of drugs known as norepinephrine reuptake inhibitors, which were developed for the purpose of treating disorders ranging from ADHD to narcolepsy and depression. Norepinephrine also plays a role in converting white adipose tissue into brown adipose tissue via an uncoupling protein 1 (UCP-1) mediated mechanism.
A carbohydrate polymer comprised of three to ten simple sugars connected through glycosidic bonds.
Surface of one's tongue. Used to describe a person's taste preferences.
A diet based mainly on foods presumed to be available to paleolithic humans. It includes vegetables, fruits, nuts, roots, meat, and organ meats while excluding foods such as dairy products, grains, refined sugar, legumes, and other processed foods.
PGC-1α (Peroxisome proliferator-activated receptor gamma coactivator 1-alpha)
The master regulator of mitochondrial biogenesis. Endurance exercise has been shown to activate the PGC-1α gene in human skeletal muscle. It is strongly induced by cold exposure, linking this environmental stimulus to adaptive thermogenesis. Recently PGC-1a has been implicated as a potential therapy for Parkinson's Disease by conferring protective effects on mitochondrial metabolism.
It is the opposite of a homeotherm. Organisms who do not use metabolism to maintain a certain body temperature. Often they can have variance in body temperature depending on the ambient temperature.
Of or relating to the period immediately after a meal.
Refined carbohydrates are forms of sugars and starches that don't exist in nature. They do come from natural whole foods, but they have been altered in some way by processing to "refine" them. Processing methods include industrial extraction, concentration/purification, and enzymatic transformation which removes many essential vitamins, minerals, and fiber.
Regulatory T Cells
Also known as T regulatory cells or Tregs. A component of the immune system that suppress immune responses of other cells. This is an important "self-check" build into the immune system to prevent excessive reactions. Regulatory T cells come in many forms with the most well-understood being those that express CD4, CD25, and Foxp3 (CD4+CD25+ regulatory T cells).
Cellular respiration is the process by which oxygen is utilized to generate energy inside of the mitochondria.
Resveratrol falls into a category of compounds known as stilbenoids, which includes another notable compound known as pterostilbene, and is produced naturally by several plants in response to injury or when the plant is under attack by pathogens such as bacteria or fungi. Resveratrol exerts its effects through sirtuin 1 (SIRT1), which is an enzyme that deacetylates proteins and thereby contributes to cellular regulation (including autophagy). **Food sources include**: the skin of grapes, blueberries, raspberries, and mulberries. **Resveratrol Autophagy** ↑ Detacetylases (especially SIRT1) → ↓ Protein Acetylation → Autophagy
Respiratory quotient. RQ=CO2 eliminated/O2 consumed. Used in calculations of basal metabolic rate (BMR) when estimated from carbon dioxide production. Such measurements, like measurements of oxygen uptake, are forms of indirect calorimetry. It is measured using a respirometer.
A disease caused by a deficiency of vitamin C. Humans and certain other animals require vitamin C from the diet in order to synthesize collagen. Scruvy can cause spongy gums, bleeding from the mucous membranes, and eventually, loss of teeth and open suppurating wounds form impaired wound healing.
The condition or process of deterioration that occurs with age. Cells that acquired enough damage can become senescent which means they are not metabolically active and do not serve a function. Moreover, they can release inflammatory cytokines which can then lead to the damage of neighboring healthy cells.
One of the sirtuin protein family members, SIRT1 is an enzyme activated by resveratrol, as well as fasting, and deacetylates proteins that contribute to cellular regulation (reaction to stressors, longevity).
A carbohydrate consisting of a large number of glucose units joined by glycosidic bonds. This polysaccharide is produced by most green plants as an energy store and is the most common carbohydrate in human diets, contained in large amounts in staple foods such as potatoes, wheat, maize (corn), rice, and cassava. Pure starch is a white, tasteless and odorless powder.
A class of cholesterol lowering drugs that inhibit the enzymes HMG-CoA reductase which plays a central role in the production of cholesterol.
A telomere is a region of repetitive nucleotide sequences at each end of a chromosome, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes. Telomeres are disposable buffers at the ends of chromosomes which protect genes next to them from being truncated. Over time, due to each cell division, the telomere ends become shorter. They are replenished by the enzyme, telomerase reverse transcriptase.
Theory proposed by Dr. Bruce Ames which proposes that when the body is deficient in a micronutrient it will allocate its scarce supply to enzymes necessary for short-term survival and reproduction at the cost of long-term survival enzymes. This may result in the acceleration of the aging process.
Type A and Type B personality theory
Type A and Type B personality theory describes two contrasting personality types. In this theory, personalities that are more competitive, outgoing, ambitious, impatient and/or aggressive are labeled Type A, while more relaxed personalities are labeled Type B.
Uncoupling protein 1 (UCP1)
A protein found in the mitochondria of brown adipose tissues (BAT) previously known as thermogenin. Part of the mechanism utilized by brown fat to generate heat via non-shivering thermogenesis, which is especially important for heat loss that would otherwise occur in neonates due to their high surface area-volume ratio.
A compound, CO(NH2)2, occurring in urine and other body fluids as a product of protein metabolism.
Volatile organic compound. An organic chemical that has a high vapor pressure at ordinary room temperature.
Molecules such as plant polyphenols, which are produced in response to stress experienced by the plants, can have a longevity-conferring effect on consumers of the plant. Compounds like polyphenols themselves similarly are beneficial, in part, because they trigger mild cellular stress that induces beneficial stress response pathways.
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