• The Cold Shower, Hot Pepper, Brown Fat Weight Control Plan

    Posted March 24, 2015: by Bill Sardi

    Key points

    • In the human body white fat predominates over brown fat by volume. White fat stores energy as triglycerides and is abundant in the midsection and thighs.  Brown fat expends energy in the form of heat and is located in the neck and collarbone area.
    • Brown fat implanted into animals improves their ability to utilize insulin.
    • Brown fat positive subjects don’t gain weight with advancing age.
    • For many years it was mistakenly believed the adult human body had no measurable amount of brown fat. PET scans began to reveal brown fat about a decade ago.  The drawback of PET scans is that they only reveal activated brown fat.
    • Obese individuals exhibit a slightly reduced body temperature during the day compared to lean individuals which results weight gain.
    • More than 60% of the variance in body mass and body fat is determined by brown fat.
    • Cold temperature, insulin, iron, thyroid hormone and adrenal stress hormones (norepinephrine) activate brown fat. Iron deficiency and beta blockers reduce brown fat volume.
    • There are no drugs approved to activate brown fat. A number of nutraceuticals activate brown fat: resveratrol, garlic, capsaicin (red pepper), melatonin, fish oil, curcumin, fucoxanthin from seaweed, green tea
    • The healthy Mediterranean and traditional Japanese diets include foods, spices and teas that activate brown fat.

    Introduction

    A previously overlooked type of fat in the body that generates heat and is associated with leanness is now being avidly investigated.

    Brown fat, also called adipose tissue (BAT), along with white fat are the two types of fat found in mammals.  An average adult has about 30 billion white fat cells, which accounts for about 30 lbs. of total weight, but far less brown fat.  Brown fat’s major function is to generate body heat while white fat’s role is to store energy. [Journal Cellular Physiology March 11, 2015]  White fat stores energy in the form of triglycerides. [Frontiers Medicine Jan 8, 2015]

    When brown fat is implanted in animals, their metabolism (insulin sensitivity and glucose tolerance) is improved. [Journal Clinical Investigation Jan 2013]  So brown fat’s health benefits extend beyond weight control.

    In fact, brown fat is not just beneficial for the waistline.  It is also considered “a powerful therapeutic avenue to ameliorate high cholesterol and protect from arterial disease.” [Nature Communications March 2015]

    The renewed scientific interest in heat-generating brown fat is due to the relatively recent recognition that humans have an abundant amount of this fat.

    For many years it as mistakenly believed that brown fat was only present in babies still in the womb and disappeared after birth. It is now known that the majority of humans have brown fat.

    Over the past decade when PET scans began to be used to visualize the location, size and growth of tumors by the infusion of radioactive sugar, areas around the neck and collarbone exhibited active metabolic activity and uptake of sugar, evidence of heat and energy expenditure that was identified as brown fat.  The mistaken idea that brown fat is not found in adult humans was erased. [Current Diabetes Reports April 2010]

    Brown fat is more commonly detected in women and in younger and leaner individuals.  It is now believed that brown fat can be activated to manage body weight. [Current Opinion Clinical Nutrition Metabolic Care Jan 2011; American Journal Physiology Endocrinology Metabolism Oct 2010]

    Brown fat is not only distinguished from white fat by its color but also by its iron content that gives it a tan to dark red color.  The fat that builds up around the midsection and thighs is white fat while brown fat is mainly found around the collarbones and neck bones.  [Medical News Today Sept 15, 2014]

    PET scans reveal brown fat

    As technologically advanced as PET scans are, they underestimate the prevalence of brown fat because they only measure activated brown fat. [Current Opinion Clinical Nutrition Metabolic Care Jan 2011]  And of course, PET scans expose subjects to a radiation hazard.  So they should not be utilized to routinely screen for activated brown fat, which is a transient condition anyway.

    To prove the presence of brown fat in healthy human adults a group of 162 volunteers underwent PET scan after 2 hours of exposure to cold temperature.  Cold-activated brown fat was detected in 41% of subjects with the brown fat-positive group being younger and leaner.  Brown fat decreased with advancing age, being more than 50% in the 20s but less than 10% in the 50s and 60s.  [Obesity Sept 2011]

    However, even among those individuals who do not exhibit activated brown fat on a PET scan, researchers say PET scans are not optimal for imaging brown fat and that regardless of PET scan status, brown fat is “highly prevalent in adult humans.” [Journal Clinical Endocrinology Metabolism Aug 2011]

    The detection of brown fat by PET scan is protective against diabetes and obesity.  [Molecular Imaging Biology Dec 2011]

    Subjects whose brown fat doesn’t readily take up sugar as visualized on a PET scan tend to have modestly higher blood sugar levels.

    PET scans reveal ~7.5% of women and 3.1% of men have activated brown fat. [New England Journal of Medicine April 9, 2009]

    Health benefits of brown fat

    While the traditional description of the origin of obesity is rooted in an imbalance between energy intake (food consumption) and expenditure (such as exercise), only now have researchers discovered a metabolic difference between the lean and obese.

    In the animal lab, mice whose brown fat has been increased or activated are lean and protected from obesity.  It is the age-related change in brown fat activation that likely explains why the young are generally lean and fat mass increases with advancing age in adulthood.  [Journal Cell Physiology March 11, 2015]

    About 50% of used energy is used to maintain a constant body core temperature.  For the first time researchers now report that lean individuals exhibit a slightly higher core body temperature (100.22 Fahrenheit compared to 98.24 F for obese individuals) during the day (11:30 AM to 5:00 PM) but not at night.  This body core temperature difference would account for the accumulation of ~4.4 lbs. (2.0 kilograms) of body weight per year.  [Chronobiology International 2015]

    Body temperature chart

    Just a few pounds of weight difference in a year between those who have activated brown fat in their body and others who do not may sound almost trivial to a person who is 50, 75, even 100 pounds overweight.  However, in one study it was determined that brown fat activity explains 64% of the variance in body mass and 60% of the variance in body fat from individual to individual.  This is very compelling.

    In one study only 3 out of 15 morbidly obese subjects exhibited cold-temperature induced brown fat activity [PLoS One Feb 24, 2011]

    The current turn away from fat phobia and towards avoidance of refined sugars and carbohydrate intake (bread, rice, pasta) is now well substantiated to produce leaner and healthier humans.  [Cardiovascular Journal Africa 2014] However, unexpectedly, a low carbohydrate/high-fat diet did not produce leaner animals in the laboratory due to an increase in brown fat activation.  Carbohydrate avoidance worked by other mechanisms. [PLoS One June 13, 2012]  But another study shows limitation of carbohydrates did improve brown fat volume. [Nutrition April 2014.  Indeed, adults with diabetes have been shown to choose foods that provide higher amounts of sugar and carbohydrates and lower in fat.  [Nutrition Diabetes Feb 2014]

    And here is a striking fact: brown fat-positive subjects do not gain weight with advancing age! [Obesity Sept 2011]

    Individuals with constitutional thinness, even at temperature-neutral conditions, have a 16.7 times greater glucose uptake in  brown fat compared with normal weight control individuals.  [Journal Clinical Endocrinology Metabolism March 2013]

    Conversion of white fat to brown fat

     What increases brown fat?

    Cold temperature, iron and lack of iron deficiency, insulin that facilitates iron availability, thyroid hormone and norepinephrine, an adrenal stress hormone, are involved in the conversion of white fat to brown fat as well as the activation of brown fat to produce heat.

    Cold temperature

    Brown fat is known as hibernation fat.  This is because cold temperature increases metabolic activity and brown fat uptake of sugar (glucose from the liver) is 10-15 times higher in cold versus normal room temperature.  [Current Opinion Lipidology Feb 2011]

    Brown fat is greater in hibernating animals due to its activation by an internal antioxidant enzyme called heme oxygenase-1.  Modest biological threats such as radiation and food deprivation activate an internal guardian of genes called heme oxygenase-1 via the Nrf2 gene activator. [Canadian Journal Physiology Pharmacology March 2010]

    Exposure to cold temperature, thyroid hormone supplementation and implantation of brown fat, have been shown to improve sugar (glucose) tolerance and insulin sensitivity (ability of cells to utilize insulin).  [Frontiers Physiology Jan 2015]

    In a cold temperature climate researchers in the Netherlands found 96% of subjects were brown-fat positive. [New England Journal Medicine April 9, 2009]

    When adults were tested there was no detectable uptake of radioactive sugar into tissues at high temperature, only at cold temperatures.  [Diabetes July 2009]

    Brown fat is higher (13.7% vs. 4.1%) in January through March when outside temperatures are low compared to the rest of the year. [Journal Nuclear Medicine Aug 2003]

    Anesthesia, which lowers body temperature, or exposure to cold temperature, increases the uptake of radioactive sugar into fat cells by 14.0-fold and 4.9-fold respectively.  [Journal Nuclear Medicine July 2004]

    The ability of stress hormones (norepinephrine) to activate brown fat is compromised in low temperature environments. [American Journal Physiology July 1988]

    One theory is that obese people have greater amounts of fat and may therefore feel less cold, meaning they need less brown fat activation. [Brazilian Archives Endocrinology & Metabolism Dec 2014]

    cold-vs-hot-temp

    PET scan showing activated brown fat (left) in cold environment versus warm environment.

    Brown fat and the diet

    A number of dietary factors affect the conversion of white fat to brown fat as well as the activation of brown fat to produce heat.

    The intake of animal fats decreases thermogenesis (heat generation) compared to consumption of vegetable oils.  Animals given lard do not generate as much heat.  [Journal Nutrition April 1995]

    Consumption of fish oil has been shown to increase brown fat in lab animals. [European Journal Nutrition Jan 23, 2015]

    Iron accumulation increases in brown fat. [Histology Histopathology April 2013]

    Insulin is crucial for the development of brown fat.  [PLoS One Oct 14, 2014]  Iron loading in brown fat has been observed after treatment with insulin. [European Journal Histochemistry 2003]

    Iron-deficient animals given supplemental thyroid hormone exhibit an increase the amount of brown fat in their tissues. [Pediatric Research Oct 1985]

    Experiments show that oxidation of fats is required for cold-induced heat generation (thermogenesis) in brown fat. [Cell Reports Jan 13, 2015]  Therefore, iron-induced oxidation of fats suggests iron and easily oxidized fats such as from fish and flaxseed oil are companions in the activation of brown fat.

    Mechanism of activation

    The molecule that facilitates release of heat energy from brown fat is called uncoupling protein-1 (UCP-1).  It is found in the mitochondria (power generating bodies) of brown fat cells and generates heat.  The activation of brown fat starts with easily- oxidized fats, such as omega-3 fatty acids (fish oil, flaxseed oil) and the release of norepinephrine, a stress hormone.  The white fat cell is transformed from an energy-conserving to an energy-expending state (brown fat cell). [Wikipedia]

    Drugs or other agents that target uncoupling protein-1 (UCP-1) in the mitochondria of living cells are being considered for the treatment of obesity and adult-onset diabetes. [Frontiers Physiology Jan 2015]

    What blocks activation of brown fat?

    Two factors inhibit production and/or activation of brown fat: iron deficiency and beta blockers.  Activated brown fat is reduced by 30% when patients are given a beta blocker.  [Journal Nuclear Medicine July 2004]

    In 90% of subjects given a beta blocker drug, brown fat does not uptake radioactive sugar as observed in a PET scan. [British Journal Radiology Aug 2009]

    Drugs to activate brown fat

    Activation of brown fat is a therapeutic approach to obesity.

    Numerous researchers have proposed the development of drugs that stimulate brown fat.  However, pharmacologists say the commercialization of technologies to harness brown fat synthesis “are currently still lacking.” [Hormone Molecular Biology Clinical Investigation July 2014]

    In a landmark report entitled “Brown Adipose (fat) Tissue and the Cold War Against Obesity” published in the journal Diabetes, researchers lament that “pharmacological strategies aimed at increasing energy expenditure have not delivered on the promise of efficacy or safety when translated from animal models to humans.”  High-dose thyroid hormone or other agents that activate the sympathetic nervous system (norepinephrine), while effective at increasing energy expenditure, result in side effects that eliminate them from practical use in the obesity clinic.  Even though exposure to cold temperature may activate brown fat heat energy researchers say this may also result in increased hunger and “not be so cool after all!” [Diabetes Dec 2014]

    Ironically, physicians widely prescribe a class of drugs that interfere with brown fat activation.  Beta blockers block the uptake of sugar into brown fat. [European Journal Nuclear Medicine Molecular Imaging July 2007]  Millions of Americans take beta blockers every day to help control blood pressure, heart rate and glaucoma.  They unwittingly have no idea this drug produces significant metabolic disturbance that can lead to obesity, insulin resistance and other health problems.

    But why must brown fat activators be expensive and problematic synthetic drugs?

    There are a number of nutraceuticals (aka dietary supplements) that are documented to exert beneficial effects for the production and activation of brown fat.  These include but are not limited to resveratrol, curcumin, EGCG green tea extract, garlic, melatonin, capsaicin from red pepper and Fucoxanthin, a seaweed extract.

    Here is some of the published science that substantiates the use of nutraceuticals in brown fat maintenance:

    Resveratrol

    Researchers only recently recognized resveratrol’s ability to increase brown fat heat generation. [Molecules Nov 14, 2014]

    Resveratrol-fed laboratory mice experience formation of brown fat via activation of AMPK, a protein that is an energy-sensing molecule. [International Journal Obesity March 12, 2015]

    Resveratrol is known to activate the Sirtuin-1 survival gene and is a molecular mimic of a limited calorie diet (influences the same genes that food deprivation does).  Activation of the Sirtuin-1 survival gene enhances brown fat function and enhanced insulin sensitivity and glucose tolerance even on a low-fat diet in laboratory mice. [Molecular Metabolism Dec 18, 2014]

    Garlic

    In an animal laboratory, garlic added to a fed a high-fat diet increased the uncoupling protein-1 (UCP-1) and the AMPK energy sensing molecule and stimulated brown fat. [Journal Nutrition Nov 12, 2011]

    Laboratory mice fed a high-fat (lard) diet with garlic increases urinary excretion of epinephrine and norepinephrine and brown fat mass. [Journal Nutrition Feb 1999]

    Melatonin

    Brown fat mass increases and is activated in animals given melatonin. [Obesity Reviews March 2011]

    Resveratrol + melatonin synergistically increases heme oxygenase the internal antioxidant enzyme that activates brown fat. [Journal Pineal Research March 2011]

    Fucoxanthin

    Fuxoxanthin, a brown carotenoid pigment found in seaweed, has been found to reduce abdominal “belly” white fat and reduces the body weight of laboratory mice via production of the UCP-1 uncoupling protein mentioned earlier in this report.  [Biotechnology Journal Sept 2010; Molecular Nutrition Food Research Dec 2009; Biochemistry Biophysical Research Communications July 2005] Fish oil combined with Fucoxanthin also appears to work well together in weight control. [Journal Agriculture Food Chemistry Sept 2007]

    Fucoxanthin also improves insulin resistance and helps to normalize blood glucose levels. [Journal Oleo Science Feb 2015]

    Another mechanism by which Fucoxanthin works to overcome weight gain is activation of internal antioxidant defenses compromised by a high-fat diet via activation of the Nrf2 gene transcription factor.  [Nutrition Research Practice Dec 2013]

    Fish oil

    Fish oil and the amino acid taurine also are a good combination to reduce white fat. [Journal Food Science June 2012]

    Curcumin

    Curcumin, an extract obtained from turmeric spice, is known to exert its influence on brown fat by activating mitochondrial release of energy. [FASEB Journal April 2014]

    Green tea (EGCG)

    A decade of research confirms that green tea, in particular an extract of green tea (EGCG- epigallocatechin gallate) reduces fat mass, body weight, fat absorption, triglycerides, cholesterol, insulin and increases heat generation (thermogenesis) in lab animals. [Molecular Nutrition Food Research Feb 2006]

    EGCG green tea extract was found to increase uncoupling protein-1 in white fat and slowed the accumulation of body fat in high-fat fed mice without reduction of food intake. [International Journal Obesity June 2005]

    Capsaicin

    Capsaicin is the hot spicy component of red pepper.  Capsaicin ingestion activates brown fat in humans. [American Journal Clinical Nutrition April 2012]

    In a human study, 6-weeks of daily capsaicin supplementation mimicked the effect of repeated cold exposure in the recruitment of brown fat. [Current Opinion Clinical Nutrition Metabolic Care Nov 2013; Journal Clinical Investigation Aug 2013]

    Capsaicin is known to activate brown fat among individuals who have brown fat but not among those who do not. [Current Opinion Lipidology Feb 2013]

    Final notes

    The brown fat paradigm to overcome obesity has yet to take off.  Such a revolution, which was scientifically posited in the 1970s and 1980s got side-tracked when it was mistakenly concluded brown fat was unimportant in adult humans because they have low numbers of brown fat cells.

    The second brown fat renaissance for weight management was called for in 2009. [Obesity Reviews May 2009]  It too has yet to materialize.  It took the National Institutes of Health over 50 years to finally conduct a workshop entitled “Exploring The Roles of Brown Fat in Humans (February 25-26, 2014). [Cell Metabolism Sept 2014]

    Such a revolution appears to have stalled due to the lack of commercialization of the idea.  Yet safe and economical nutraceuticals abound that markedly increase the numbers and activation of brown fat cells.

    While the brown fat revolution may have stalled, physicians would certainly be attracted to the idea of surgically implanting brown fat as has been done successfully on an experimental basis.  A tragic failing of western medicine is what is healthy must be obscenely profitable to gain physician adoption.

    The public appears to be waiting for physicians to prescribe and physicians appear to be waiting for Big Pharma to introduce synthetic drugs to do what nutraceuticals have already been proven to do.

    It is not like brown fat is a totally unproven idea.  Indeed, it is no wonder there is such a lean population in Japan. The traditional Japanese diet includes green tea, seaweed and fish oil that are strong promoters of brown fat.  The same goes for the Mediterranean Diet centered on wine (resveratrol), garlic and fish.

    The definitive book on the topic of brown fat, The Brown Fat Revolution written by James R. Lyons MD, was published in 2009 and has not received rave reviews at Amazon.com.  [Amazon.com] So adoption of dietary and supplemental measures to activate brown fat is slow to materialize.

    There are over ten-thousand published online reports about brown fat at the National Library of Medicine dating back to the 1940s.  Differences between the physiological activity of brown and white fat were presented in 1947. [Science Jan 31, 1947]  There is no shortage of science.

    In reality, the brown fat revolution began long ago.  Today it is called the Mediterranean Diet and the traditional Japanese diet.  It doesn’t need to be focused around any drug such as Lipitor and statin drugs that were the focus of the cholesterol-phobic era.  It doesn’t need to be “as seen on TV.”

    America was once a lean population.  That dates back to the 1970s.  Then came high fructose corn syrup and other obesogens like bisphenol A.  The masses, given choices between what tastes good and what is healthy, will likely continue to opt for the former rather than the latter.

    There will continue to be misdirection.  The landmark study that concluded reduced-calorie diets were equally ineffective in achieving weight loss completely overlooked thermogenesis and brown fat. [New England Journal Medicine Feb 26, 2009]

    Individuals don’t need to wait for government to fortify foods with brown fat stimulators or physicians to prescribe heat-generating drugs or implant brown fat in operations that are paid by insurance. Jump in a cold shower in the morning to activate your brown fat cells.  Sprinkle some red pepper and garlic powder on your breakfast eggs.  Drink green tea.  Take a resveratrol pill with your evening meal.  Studies show you will get a better night’s sleep as well. [Neuroscience Letters March27, 2003] — ©2015 Bill Sardi, Knowledge of Health.

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