The ability of the human body to process nutrients and convert this input to energy and raw materials for our cells is truly remarkable. From a biohacker's point-of-view, modulation of metabolism by diet/intermittent-fasting, and exercise are powerful ways to modulate one's metabolic state.
Metabolic activites are carried out in virtually every cell, in every tissue of the body. However, there is a lot of individual variability in metabolism. For example, a recent paper in Cell showed that increases in blood glucose after identical meals differs hugely among individuals.1This indicates that blanket recommendations for diet may fall short for many individuals, and greater personalization of nutritional recommendations should be the norm. Furthermore, many chronic diseases have their roots in metabolic dysfunction. To this end, we will describe some basic anatomical and cellular constituents of human metabolism, and steps that can be taken to modulate your metabolism.
While the entire body participates in the metabolic process, there are several key organ systems that play particularly important roles as reservoirs of energy, that are mobilized when blood glucose levels fall. In particular, the body's adipose tissue (fat), liver, and muscles are important sites of metabolic activity and reserves of energy.
During fasting, energy is provided to the body in several ways. Glycogen (branched chains of glucose molecules) stores in the liver are mobilized to increase glucose in the blood stream. Fatty acids stored in adipose tissue, are broken down and transported throughout the body. These fatty acids are either made into glucose, or are converted into ketone bodies. These ketone bodies are very efficiently used in the Citric Acid Cycle (described below) to produce energy.
Free glucose in the blood is not directly utilized as energy by the cell. Rather, ATP is the final "energy currency" in biological circuits. The production of ATP from glucose proceeds through several cellular processes: glycolysis, wherein glucose is broken down into pyruvate; pyruvate is converted to acetyl-CoA (not pictured); the citric acid cycle produces NADH; and this NADH is sent through the electron transport chain, where the H+ ions are stripped from NADH, and used to produce ATP through an elaborate mechanism.
This breakdown of glucose and the electron transport chain are perhaps the most well-defined biological processes. A full treatment of this process is by no means presented; however, it is easy to appreciate just how complex the metabolism of glucose is, and how many different proteins play important roles. And it is likely natural genetic variation in the function of these proteins, and experience-dependent modulation of these proteins, contributes to individual differences in metabolism.
Glycolysis: breakdown of glucose into substrates used to produce cellular energy
The Citric Acid Cycle: converting glucose to NADH
The Electron Transport Chain: using NADH to drive the production of ATP
A person's metabolic state are influenced by various factors such as nutrition and exercise. The complex interplay of these factors have effects on cognition as well as prevention from various chronic diseases and conditions such as heart disease and metabolic syndrome.
The powerful influence of our diet on our cognitive processes is just starting to be discovered. Advances in molecular biology are allowing us to uncover how certain nutrients can support the function of synapses - the neuron-to-neuron junctions that are the basis of the nervous system, and improve cognitive performance. In particular, supplementation with omega-3 fatty acids such as DHA can modulate neuronal signaling, and preliminary evidence suggests DHA may improve cognitive function. (Learn more)
Metabolism is also closely linked with aging at a cellular level. In particular, the efficiency of mitochondria, the powerhouse of the cell, are closely linked with aging.
Since 1956, the free radical hypothesis of aging has suggested that aging may be driven by biological stress and damage that accumulates through free radical molecules. Free radicals are compounds that have an excess of electrons, which can readily react with surrounding molecules. These reactions result in molecular damage to proteins, lipids, and other molecules that make up cells. The Mitochondrial Free Radical Theory of Aging (MFRTA) is one of the leading theories of how aging occurs on a biological level. Defining the molecular events and the pathways of aging are still contentious in the study of biology and medicine. One of the prominent theories in the space is the mitochondrial proliferation hypothesis, put forth by Aubrey de Grey. (Learn more)
Optimizing metabolism is important for physical and cognitive health. Firstly, as described above, individual differences in metabolism render blanket recommendations less effective for particular individuals. So to truly optimize metabolism, a biohacker's mindset is critical. Secondly, anybody can benefit from an improved metabolic state. Many of the most deadly chronic diseases are hypothesized or proven to originate from metabolic dysfunction. In diseases ranging from heart disease, to type II diabetes, and Alzheimer's disease, poor metabolic processing plays a key role in disease progression.2,3,4
There are several strategies for modulating metabolism, including variations of fasting, exercise and dieting.
Dieting and nutrition are deeply individual endeavors that should be guided by your goal and what regimen fits best with your lifestyle. (Learn more)
Intermittent fasting (IF) is an umbrella term for forms of fasting that cycle between periods of fasting and feeding. There's a growing body of science behind IF and other forms of caloric restriction showing health benefits including longevity, improved metabolic state, improved insulin resistance, and cognitive improvement. Furthermore, intermittent fasting has been shown to improve symptoms in patients with medical problems including cancer and auto-immmune diseases. (Learn more)
The sirtuin proteins are important sensors of metabolic state, and emerging evidence indicates that increasing sirtuin function can have longevity and metabolic benefits. One of the strategies to increase sirtuin function is by increasing nicotinamide adenine dinucleotide (NAD) - a cofactor that binds to sirtuin proteins and allows them to function properly. However, the best method to modulate NAD for longevity and health benefits in humans is still disputed. (Learn more)
NAD+/NADH and NADP+/NADPH are electron carriers. And they're valuable because electrons play critical roles in carrying out many reactions in the body. NADH is notably known for it's role in generating ATP, which serves as fuel for the body. NADPH is generally known for its role as a reducing agent for mitigating oxidative stress. (Learn more)
Metformin is a drug that is used to increase the body's sensitivity to insulin. While normally its usage is limited to diabetes, recent research has implicated that it may be beneficial for enhancement purposes in people that do not have diabetes. A 15-year long observational study showed that metformin was useful for preventing metabolic deficits related to diabetes, and a number of studies have shown that metformin was useful for prolonging lifespan. (Learn more)
Exercise has been studied through decades of scientific research and is known to trigger widespread a positive effect on various aspects of cognition and metabolism. With reference to cognition, exercise increases concentrations of neurotrophic factors that are instrumental for maintenance of brain tissue. Improvements in memory, mood and creativity have been witnessed in individuals following exercise. With reference to metabolism, exercise induces hormonal changes that are important for homeostasis and prevention of lean muscle breakdown. (Learn more)
There's been debate in the community about whether human growth hormone supplementation is as effective or more effective than sex steroid therapy. In modern medicine, human growth hormone is generally used for people with growth deficiencies, or older individuals who have a decline in human growth hormone levels. On the other hand, sex hormone therapy is typically used for cancer recovery and for treating symptoms of menopause and aging. (Learn more)
Zeevi, D., Korem, T., Zmora, N., Israeli, D., Rothschild, D., Weinberger, A., . . . Segal, E. (2015). Personalized Nutrition by Prediction of Glycemic Responses. Cell, 163(5), 1079-1094. doi:10.1016/j.cell.2015.11.001
Poirier, P., Giles, T. D., Bray, G. A., Hong, Y., Stern, J. S., Pi-Sunyer, F. X., & Eckel, R. H. (2006). Obesity and Cardiovascular Disease: Pathophysiology, Evaluation, and Effect of Weight Loss: An Update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease From the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation, 113(6), 898-918. doi:10.1161/circulationaha.106.171016
Leverve, X. M., Guigas, B., Detaille, D., Batandier, C., Koceir, E. A., Chauvin, C., . . . Wiernsperger, N. F. (2003). Mitochondrial metabolism and type-2 diabetes: a specific target of metformin. Diabetes Metab, 29(4 Pt 2), 6s88-94.
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