Metabolism - for the Centenarian
The 2016 Metabolic Therapeutics Conference on Nutritional Ketosis was held last February and all the top scientist, MDs, nutritionists, and reserchers were on hand for open discussions and lectures. Many of the key-note people are referenced on this website. Lecturer's - Videos.
Another resource is the Bio-Hackers who are exploring all the new Science. Medicine by Chemistry is losing out to Nutrigenomics. Ex: Phamaceuticals - a failed Experiment These bio-hackers are represented at Biohacker Summit.
Metabolism, the sum of all chemical processes by which a plant or an animal uses food, water, etc., to grow and heal and to make energy. Most light-sensitive organisms on earth have acquired an internal system of circadian clocks allowing the anticipation of light or darkness. In humans, the circadian system governs nearly all aspects of physiology and behavior.
Dr. Panda and Dr. Patrick discuss this very important regualatory function ... Circadian Rhythm
(1,1a) It is real and we need to stopping eating when in the
Sleep, Repair and Maintenance mode and eat when we are active.
Completely different genes are active during these periods.
Example: Melatonin's role as a circadian modulator in memory processing. (1c)
The body CLOCKs are controlled by light and food. Circadian clocks are encoded by a transcription-translation feedback loop that aligns energetic processes with the solar cycle. (1b)
(Note 1) For example, the bright sunlight turns on genes that prepare the body for the day's activity, prepares the immune system and syncs
with other system clocks. The liver clock turns on genes when food arrives and then starts up the bodily cycles and nutritional pathways. A
Traffic Jam can occur when these clocks are not in sync.
The body's organs and the gut microbiota each have their own clocks that respond to imminent conditions. (1,1a,6)
- The sum of the processes in the buildup and destruction of protoplasm; specifically : the chemical changes in living cells by which energy is provided for vital processes and activities and new material is assimilated.
- The sum of the processes by which a particular substance is handled in the living organism. Millions of chemical processes are occurring every second in every living organism.
- Life in General: the sum of the metabolic activities taking place in a particular environment, ex.
the metabolism of a house.
- Proteins - extensive mechanisms to digest, metabolize, and eliminate. An essential nutrient with high satiety to avoid excess intake. Multiple metabolic pathways.
- Fats - unlimited energy storage for survival and metabolic energy. A passive essential nutrient with multiple metabolic pathways and storage systems.
- Carbs - low evolutionary exposure, highly toxic response and requires rapid clearance. Insulin is the only safety mechanism. A non-essential nutrient.
- Sleep/Fasting - A minimum requirement as a condition of life.
Adaptive Survival to Environmental Nutrition
- Melatonin, a hormone found in animals that is critical in regulating our relationship with the light-dark cycle down to the cellular level (including fungi, and bacteria), and regulates over 500 genes. (3)
- The circadian rhythm turns on and off genes to regulate DNA repair, and it is now shown that DNA repair occurs during fasting periods, i.e. "Sleep and Time-Restricted Feeding". (4)
- There is a master clock and it resets and turns on and off genes throughout the day. There are internal clocks that regulate organ clocks and body chemistry by regulating 3-6000 gene expressions on a daily cycle. This is approximately 25% of our genes on a clock. Bad diet effects these clocks and time-restricted feeding (TRF) resets these CLOCKs. (1,1a,3,4,5,6) (Note 1)
Key Knowledge: You are turning off your immune system with a poor diet. The body favors short-term survival over long-term health. This trade-off accelerates aging-associated diseases, such as cancer, cardiovascular disease, immune dysfunction, and cognitive decline. High carbohydrate diets shut down the bodies own antioxidant defense genes.
Dr. Phinney, . Dr. Volek, . Dr. Champ, . Dr. Ames, , Dr. Lustig, , Dr. Saul, , Dr. Perlmutter, . Dr. Levy, , Dr. Patrick, ,
Acetyl-CoA is mainly generated by combustion of glucose, fatty acid, and proteins. When in excess, acetyl-CoA can be used to make sterols and fatty acids, and can also conjugate to proteins, forming acetylated protein products. In long term fasting or starvation, acetyl-CoA can be used to form ketone bodies that are needed for brain function. Under normal conditions, acetyl-CoA is metabolized to provide energy via Citric Acid Cycle (aka, Krebs Cycle, TCA cycle) and oxidative phosphorylation inside mitochondria.
Triglycerides (TR) and Lipoprotein Transport,
TRs are fatty acids esterified with glycerol, (Wiki) and seem to be a primary area of concern in the aging/ageing process. Lipoproteins are the Bulk Lipid Blood Transport metabolism of the body. (11) Triglycerides come up all the time with doctors and is a
WTF moment because it is not well understood
why they are high, or even how important it is.
They are a marker for Metabolic Syndrome. From the second diagram, we see that these triglycerides are directly involved with the mitochondria and are
a source of energy in producing ATP.
Humans cannot survive without the
Lipoprotein metabolic pathway (10). We make everything we need; therefore, if our metabolism is of whack, we need to know what went wrong
with our diet. Cells and organisms use lipoproteins to move hydrophobic lipid molecules, which are not water soluble, through the aqueous blood and tissue lymph environment.
Dr. Stephanie Seneff - Cholesterol Sulfate has shown that without sulfur in our diet, the cholesterol sulfate - vitamin D - sun cycle does not work.
Cholesterol must become water soluble by the addition of sulfur. Dr. Seneff proposes that we are actually
Lipoprotein particles are defined by their complement of associated apolipoproteins (Apo) and their content of cholesterol (CHOL), triglyceride (TG) and phospholipid that each particle carries. This protein and lipid content defines the particles buoyant density and subdivides them into 4 major classes: high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), and chylomicrons. (11,11a)Informational brochure by abcam Lipid Metabolism pathway.
Mitochondria = ATP:, Mitochondria, (12) the so-called "powerhouses" of cells, are unusual organelles found in large numbers in most multi-cell organisms in which the biochemical processes of aerobic respiration and energy production occur.
ATP, without which we would die in 15 seconds, is the focus of biological processes that produce cellular energy. B Vitamins are co-factors in the mitochondria metabolism and are required for the mitochondria to function. How Your Mitochondria Influence Your Health - Dr. Mercola and Dr. Rhonda Patrick | may/2016 (13) discuss, mitochondrial biogenesis, cancer prevention, nutrition and the current understand of cell construction and metabolism tradeoffs.
Senescence cells are causes of aging, and optimizing mtDNA (14) is important to overall metabolism. Understanding what co-factors and nutrients are necessary for mitochondria optimal function is primary. B vitamins are one such group important in mitochondrial enzyme processes. Aging, neurodegenerative disorders and metabolic disease are all linked to mitochondria. (15)
Mitochondrial Biogenesis (16) is the process by which new mitochondria are made inside of cells. Many factors can activate biogenesis including aerobic exercise, environmental stimuli (cold/heat shock), TRF (sleep/fasting), and numerous other pathways (ketones bodies, (16a)). These are directly related to the body's immune response and food response i.e. Gut Microbiome. The transcription factor PGC1-a serves as the master regulator of the process. (16b)
Carbohydrates, - A Macronutrient, however they are a
Non-essential Macronutrient. There is no known carbohytrate deficiency disease, and we
can live without this macronutrient. (Note 2) On the flip side excess carbohydrates are the cause of the modern
The Saccharine Disease (Cleave - 17a,17) started in 1956.
The Primal Blueprint Carbohydrate Curve - from Mark's Daily Apple
Mark Sisson, "Mark's Daily Apple", has been living the LCHF Diet and on his website has some of the best analysis anywhere. He summarizes...
Carbohydrate intake is often the decisive factor in weight loss success and prevention of widespread health problems like Metabolic Syndrome, obesity and type 2 diabetes.
These average daily intake levels assume that you are also getting sufficient protein and healthy fats, and are doing some amount of Primal exercise.
Also ref: ... the Centenarian Diet.
You the consumer are responsible for keeping your daily intake of
Carbohydrates below 100mg per day. And the carbs cannot be processed. For an easy reference
USDA Food Composition Databases.
The USDA has many great resources and this is one.
Count Your Carbs - Daily. (18)
Meta Analysis | Sugar vs. Obesity
Sugar Consumption vs. % Population Obesity
Hypothesis, from this chart it is indicated that there is more to the story of
Obesity over the last 60 years. This could be a case of the
Compounding Effects of Epigenetics. There have been 4 generations of
High Consumption of Carbs - Beyond a Metabolic Tolerance this defines
Carbohydrate Intolerance. We know that diet can change our gene expression through
The data is indicating that there is a threshold, 10kg/22lb per year/person, and of above this the body does not seem to be responding well to this dietary environment. Also, besides
Obesity, there is a
corresponding increase in diseases from Metabolic Syndrome and Inflammation.
Ref: Nutrigenomics and Epigenetics | contributor July/2016.
After all, insulin is not designed to
Control Glucose, it is a growth hormone and regulates fat storage and growth.
Ref: Carbohydrates and Longevity | contributor October/2016.
Fats or Lipids, - A Macronutrient - Essential, i.e. energy sources and building block for the body. ... this site - Fats. See
How to Build a Cell as
the cell membrane is a protein lipid protein structure, (19,20) with many pathways across the cell membrane. Fats are also an energy source and are part of the Ketogenesis cycle.
Simplified diagram of the three stages of cellular metabolism that lead from food to waste products in animal cells. (21,21a)
Molecular Biology, How Cells Obtain Energy from Food -Alberts B, Johnson A, Lewis J, et al, 2002 . (22)
This series of reactions produces ATP, which is then used to drive biosynthetic reactions and other energy-requiring processes in the cell. Stage 1 occurs outside cells. Stage 2 occurs mainly in the cytosol, except for the final step of conversion of pyruvate to acetyl groups on acetyl CoA, which occurs in mitochondria. Stage 3 occurs in mitochondria. (21,21a)
TRF - Time Restricted Feeding | Sleep and Fasting
Most light-sensitive organisms on earth have acquired an internal system of circadian clocks allowing the anticipation of light or darkness. In humans, the circadian system governs nearly all aspects of physiology and behavior. Ref: ... this site - Circadian Rhythm.
Time-Restricted Feeding (TRF) Is a Preventative and Therapeutic Intervention, (1,6).
- Time-restricted feeding (TRF) confines food access to 9–12 hr during the active phase.
- TRF is a therapeutic intervention against obesity without calorie restriction.
- TRF protects against metabolic diseases even when briefly interrupted on weekends.
- TRF is effective against high-fat, high-fructose, and high-sucrose diets.
DNA repair is an essential cellular function, (23) which, by removing DNA damaged cells before they mutate, contributes
crucially to the prevention of cancer. For best recovery from stress our body needs a Rest Time.
This means sleep and fasting, as the current knowledge indicate that our Circadian Rhythm controls DNA repair. The genes that control DNA repair are turned on
only when our body is fasting. This simply means that our sleep/fasting cycle is one function -
Restricted Feeding. Studies show that
Restricted Feeding is very beneficial to living organisms.
A minimum of 12 hours for a healthy recovery, is required for the
Restricted Feeding cycle. To create Strength and Endurance this cycle should be 15 hours.
Time-Restricted Feeding and Its Effects on Obesity, Muscle Mass & Heart Health | June/2016.
(Video) Limiting eating to 8-9 hours has many benefits i.e. active hours. DNA repair happens during fasting, this is new understanding of fasting physiology and our primordial rhythms. (24,25)
myCircadianClock.org app that helps you understand your body's rhythms while contributing to research. (25a)
Sleep Metabolism - Circadian Rhythm |
Metabolism Corruption by Carbohydrates
Example: Sleep and Carbohydrates
Insulin is an endocrine hormone, (26,26a) meaning it affects multiple tissues in the body. It is a growth and signaling hormone that transports glucose across the cell membrane signaling the cell to begin creating muscle glucagon. When insulin removes the excess glucose from the blood, it will also take amino acids with it. The result will be that there will be very little tryptophan getting into the brain to make melatonin which sabotages sleep. It should be noted that the Sleep/Night-Circadian oscillator genes also have this effect. Ref: ... Circadian Rhythm - our Metabolic Clock | contributor/2016.
After protein is digested, the amino acids are in the bloodstream travelling up to the brain to make important brain chemicals, one of which is melatonin. This means that we go to sleep with a near-empty melatonin gas tank, and consequently sleep poorly.
The body treats alcohol like a sugar. This means that consuming alcohol will trigger the same type of blood sugar spikes and crashes as eating sugar, white flour, etc. So if you are going to have a few drinks, you will interrupt the metabolism of sleep, hence sabotaging melatonin production.
Fat accumulation is determined by the balance between fat synthesis (lipogenesis) and fat breakdown
(lipolysis/fatty acid oxidation). (27,28)
A balanced diet intake of proteins and fats, with limited carbohydrates, (Note 3), allows the body to deplete its stores of glucose and use ketones as fuel.
High Carbohydrate intake prevents the metabolism and insulin from dipping into the fat burning zone.
Carbohydrate Intake - Prevents Fat Burning
In summary, the increasing number of enzymes and interacting partners on lipid disorders (LD) indicates that lipolysis comprises a large network of factors coordinately acting within a “lipolytic machinery”. Time Restricted Feeding and Low Carbohydrate will improve sleep.
New discoveries will augment the complexity of this machinery and disclose its involvement in the pathogenesis ofLipid-associated Disorders, ... i.e.a Fat-Accumulation Disorderas referenced in ... the Obesogenic Diet.
Ok - Now What?
Our modern society created a Nutritional Disease; therefore, we need a Nutritional Solution. Eating too many of the wrong carbohydrates too often is what causes blood sugar and insulin levels to rise, placing us at high risk for insulin resistance and Alzheimer’s Disease (Type 3 Diabetes). Our bodies have evolved to handle whole food sources of carbohydrates like peppers, broccoli, onions, and tubers etc., but our bodies simply aren’t equipped to cope with modern refined carbohydrates like refined flour and sugar. Ref: The Premise for this Nutritional Solution.
But, doctors are not trained in nutrition, medicine as we know it is in trouble, can we be better doctors than the AMA provides. We certainly can acquire the knowledge to ask better questions.
The AMA has failed in their mission. Dr. Noakes gives a good talk on the problem ...
The Great Diet Controversy: UCT - Challenge Beliefs | Dr. Tim Noakes, november/2013
(30) and Dr. Mercola & Dr. Greger on How Not To Die | December/2015.
Dr. Mercola and Dr. Chutkan talk on
Food as Medicine - The Baby Connection and the importance of Gut Health ... referred to as
Complimentary or Alternative medicine ...
Dr. Mercola and Dr. Chutkan on Gut Health | February/2017. (32)
Dr. Chutkan has a 77% success rate of taking her patients
Simple solution, avoid carbohydrates as they offer no known nutritional benefits. Carbohydrates are however packaged in food source organisms that do provide Longevity Vitamins. We want and need Phytochemicals from our Diet, otherwise we suffer from malnutrition. The symptoms of malnutrition is what this site is all about.
Our foods provide Phytonutrients, macronutrients, micronutrients (for critical DNA repair) (R1), Polyphenols, Phytosterols, Flavonoids, Lignans, Antioxidants, and Carotenoids, that do allow life to continue. Ref: 100 richest dietary sources of polyphenols. (Resource 1,2,3)
Certainly avoid processed carbohydrates, fats and oils, and packaged and processed foods. A direct result of too many carbohydrates is Insulin Resistance functional manifested as Carbohydrate Intolerance. Dr. Volek discusses his current views on the benefits of a LCHF plan - Health-Promoting Effects of a Low-Carbohydrate Lifestyle | july/2016 and this site follows this type of plan with the addition of Dr. Ames' "Triage Theory" ... the Centenarian Diet.
What path are You On?
- CLOCK: a gene encoding a transcription factor (CLOCK) that affects both the persistence and period of circadian rhythms. CLOCK functions as an essential activator of downstream elements in the pathway critical to the generation fo circadian rhythms. In humans, polymorphisms in the CLOCK gene have been associated with the increased insomnia, weight loss difficulty, and recurrence of major depressive episodes in with bipolar disorder. Ex: There are 3-5,000 genes that turn on in the liver, depending on the time of day. (1,1b,6)
- According to Encyclopedia Britannica, there are no known diseases caused by carbohydrate deficiency. The human body has no dietary requirement for carbohydrates. If fewer than 50 to 100 grams of carbohydrates are consumed daily, the body begins to convert protein and fat into glucose, a process called ketosis. We are designed to run on Ketones. Ref: ... this site - Centenarians, Exercise for Longevity.
- Benefits of Time-Restricted Feeding: (1, 6)
- Decreases in fat mass in animals fed an ... Obesogenic Diet.
- Increases in lean muscle mass when on a normal diet.
- Improvements in glucose tolerance and insulin sensitivity.
- Reduction in inflammation, improvements in lipid profile, and favorable changes in gene expression-epigenetics. (30)
- Increases in mitochondrial volume, especially in the liver and brown fat, and an increased production of ketone bodies. (31)
- Protection from mild age related hepatic steatosis. In the obese this effect was especially effective, and a 53% reduction in triglyceride accumulation was seen.
- Further restriction showed an enhancement of endurance in the context of aerobic exercise.
Restricting feeding is important to DNA repair, and allows the body's immune response to rebuild and repair bodily tissues. Therefore, we are biologically set to an eating cycle that depends on the sun. And for best
results we should at a minimum fast for 12 hours. If we can go 15 hours even better, however, that only leaves a 9 hour time slot to eat. 8-5 then fast, which is hard to do but 8-8, or 7-7 is manageable. Water only otherwise.
Satchidananda Panda - Watching Your Diet: One Click at a Time | May/2016
presents the actual facts of our eating habits. Collected from A New Study
AppTool for Circadian Rhythm: myCircadianClock.org.
Cellis a perfect lean mean machine, and we replace all of our cells regularly. Our bodies are doing this every second, plus DNA repair, and immune responses. The cell has evolved to grow, reproduce, and repair itself. 2 billion years to achieve this, then they started organizing ...
The Human - Two Biological Organisms in One.
Our favorite youTube presentations on the cell are: TED TALK: The secret, social lives of bacteria, Dr. Bonnie Bassler | april/09 (32) Chemical Conversations: How Bacteria Talk to Each Other , Dr. Bonnie Bassler | august/10 (33)
Genes are activated, mitochondrial biogenesis is turned on and with it comes the body's own antioxidant response which is used by our immune system.
This is known as Hormesis (34) a beneficial response to stresses (improved health, stress tolerance, growth or longevity).
There is lactate generation which modulates the glycolytic system, (35) molecular mediators used by the cells and all oxygen dependent energy production cycles,
(ex. obesity and insulin resistance (36)) the inflammation response is the body's diagnostic and repair response to stress, whether it is
Exerciseor the complex modern