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The question is rather straight forward: I have always been curious as to why, but cannot find an explanation online.
I can imagine that the mechanism is different for each, but why does brain tissue and red blood cells use specifically and only glucose for energy metabolism?
In the case of red blood cells: human erythrocytes (red blood cells) have no mitochondria. Since the mitochondria are the cellular site for oxidative metabolism of fatty acids, erythrocytes cannot oxidise fatty acids to release energy. The erythrocytes also cannot fully oxidise glucose (to carbon dioxide and water) because this is also a mitochondrial process, so they have to rely upon anaerobic glycolysis. The end product of anaerobic glycolysis is pyruvate, and erythrocytes reduce this to lactate (to recycle the NADH that is produced during glycolysis) and then export this lactate into the blood for further metabolism by the liver.
The brain and heart can take advantage of ketone bodies when the amount of glucose is low. These are byproducts of fat metabolism and can be converted to acetyl-coA via the citric acid cycle.
Overproduction of these products can cause pathological conditions:
When the rate of synthesis of ketone bodies exceeds the rate of utilization ,their concentration in blood increases , this is known as ketonemia. This is followed by ketonuria- excretion of ketone bodies in urine. The overall picture of ketonemia and ketouria is commonly referred as ketosis. Smell of acetone in breath is a common feature in ketosis.
Lipid catabolism provides energy mainly through fatty acid beta-oxidation. This process goes through a spiral of four mitochondrial enzymatic steps: one is catalyzed by the mitochondrial trifunctional3-ketoacyl-CoA thiolase (gene HADH). The activity of this thiolase is very low in neurons, explaining the brain need of alternative energy sources. Yang et al., JBC 1987. As previosly mentioned, developing erythrocytes eliminates mitochondria trough autophagy (mitophagy), therefore they became unable to efficiently perform lipid catabolism.
The fat-fueled brain: unnatural or advantageous?
Disclaimer: First things first. Please note that I am in no way endorsing nutritional ketosis as a supplement to, or a replacement for medication.
Disclaimer: First things first. Please note that I am in no way endorsing nutritional ketosis as a supplement to, or a replacement for medication. As you&rsquoll see below, data exploring the potential neuroprotective effects of ketosis are still scarce, and we don&rsquot yet know the side effects of a long-term ketogenic diet. This post talks about the SCIENCE behind ketosis, and is not meant in any way as medical advice.
The ketogenic diet is a nutritionist&rsquos nightmare. High in saturated fat and VERY low in carbohydrates, &ldquoketo&rdquo is adopted by a growing population to paradoxically promote weight loss and mental well-being. Drinking coffee with butter? Eating a block of cream cheese? Little to no fruit? To the uninitiated, keto defies all common sense, inviting skeptics to wave it off as an unnatural &ldquobacon-and-steak&rdquo fad diet.
Yet versions of the ketogenic diet have been used to successfully treat drug-resistant epilepsy in children since the 1920s &ndash potentially even back in the biblical ages. Emerging evidence from animal models and clinical trials suggest keto may be therapeutically used in many other neurological disorders, including head ache, neurodegenerative diseases, sleep disorders, bipolar disorder, autism and brain cancer. With no apparent side effects.
Sound too good to be true? I feel ya! Where are these neuroprotective effects coming from? What&rsquos going on in the brain on a ketogenic diet?
Ketosis in a nutshell
In essence, a ketogenic diet mimics starvation, allowing the body to go into a metabolic state called ketosis (key-tow-sis). Normally, human bodies are sugar-driven machines: ingested carbohydrates are broken down into glucose, which is mainly transported and used as energy or stored as glycogen in liver and muscle tissue. When deprived of dietary carbohydrates (usually below 50g/day), the liver becomes the sole provider of glucose to feed your hungry organs &ndash especially the brain, a particularly greedy entity accounting for
20% of total energy expenditure. The brain cannot DIRECTLY use fat for energy. Once liver glycogen is depleted, without a backup energy source, humanity would&rsquove long disappeared in the eons of evolution.
The backup is ketone bodies that the liver derives primarily from fatty acids in your diet or body fat. These ketones &ndash ?-hydroxybutyrate (BHB), acetoacetate and acetone &ndash are released into the bloodstream, taken up by the brain and other organs, shuttled into the &ldquoenergy factory&rdquo mitochondria and used up as fuel. Excess BHB and acetoacetate are excreted from urine, while acetone, due to its volatile nature, is breathed out (hence the characteristically sweet &ldquoketo breath&rdquo). Meanwhile, blood glucose remains physiologically normal due to glucose derived from certain amino acids and the breakdown of fatty acids &ndash voila, low blood sugar avoided!
Brain on ketones: Energetics, Oxidation and Inflammation
So the brain is happily deriving energy from ketones &ndash sure, but why would this be protective against such a variety of brain diseases?
One answer may be energy. Despite their superficial differences, many neurological diseases share one major problem &ndash deficient energy production. During metabolic stress, ketones serve as an alternative energy source to maintain normal brain cell metabolism. In fact, BHB (a major ketone) may be an even more efficient fuel than glucose, providing more energy per unit oxygen used. A ketogenic diet also increases the number of mitochondria, so called &ldquoenergy factories&rdquo in brain cells. A recent study found enhanced expression of genes encoding for mitochondrial enzymes and energy metabolism in the hippocampus, a part of the brain important for learning and memory. Hippocampal cells often degenerate in age-related brain diseases, leading to cognitive dysfunction and memory loss. With increased energy reserve, neurons may be able to ward off disease stressors that would usually exhaust and kill the cell.
A ketogenic diet may also DIRECTLY inhibit a major source of neuronal stress, by -well- acting like a blueberry. Reactive oxygen species are unfortunate byproducts of cellular metabolism. Unlike the gas Oxygen, these &ldquooxidants&rdquo have a single electron that makes them highly reactive, bombarding into proteins and membranes and wrecking their structure. Increased oxidants are a hallmark of aging, stroke and neurodegeneration.
Ketones directly inhibit the production of these violent molecules, and enhance their breakdown through increasing the activity of glutathione peroxidase, a part of our innate anti-oxidant system. The low intake of carbohydrates also directly reduces glucose oxidation (something called &ldquoglycolysis&rdquo). Using a glucose-like non-metabolized analogue, one study found that neurons activate stress proteins to lower oxidant levels and stabilize mitochondria.
Due to its high fat nature, keto increases poly-unsaturated fatty acids (PUFAs, such as DHA and EPA, both sold over-the-counter as &ldquobrain healthy&rdquo supplements), which in turn reduces oxidant production and inflammation. Inflammatory stress is another &ldquoroot of all evil&rdquo, which PUFAs target by inhibiting the expression of genes encoding for pro-inflammatory factors.
Neurons on Ketones: Dampen that enthusiasm!
Excited neurons transmit signals, process information and form the basis of a functioning brain. OVER-excited neurons tend to die.
The brain teeters on a balance between excitation and inhibition through two main neurotransmitters, the excitatory glutamate and the inhibitory GABA. Tilt the scale towards glutamate, which occurs in stroke, seizures and neurodegeneration, and you get excitotoxicity. In other words, hyper-activity is toxic.
Back in the 1930s, researchers found that direct injection of various ketone bodies into rabbits prevented chemically-induced seizures through inhibiting glutamate release, but the precise mechanism was unclear. A recent study in hippocampal neurons showed that ketones directly inhibited the neuron&rsquos ability to &ldquoload up&rdquo on glutamate &ndash that is, the transmitter can&rsquot be packaged into vesicles and released &ndash and thus decreased excitatory transmission. In a model of epilepsy that used a chemical similar to glutamate to induce damage, the diet protected mice against cell death in the hippocampus by inhibiting pro-death signaling molecules. On the other end of the excitation-inhibition balance, ketones increase GABA in the synapses (where neurotransmitters are released) of rats and in the brains of some (but not all) epileptic humans subjects. This increase in inhibition may confer both anti-seizure effects and neuroprotection, though data is still scant.
Then there are some fringe hypotheses. The acidity of ketones may decrease the pH of certain brain microdomains, which might be the mechanism of keto&rsquos positive effect on Type II Bipolar disorder (lots of mays and mights, I know). As keto affects the whole body, global changes due to calorie restriction and regulation of the satiety hormone Leptin are bound to alter brain function, and play a circumstantial role.
Neuroprotection? Show me the evidence!
All these molecular changes suggest that a ketogenic diet is protective against brain injury. But is there any REAL evidence?
A study with 23 elderly with mild cognitive impairment showed that a ketogenic diet improved verbal memory performance after 6 weeks compared to a standard high carbohydrate diet. In a double-blind, placebo-controlled study, 152 patients with mild- to moderate Alzheimer&rsquos disease were given either a ketogenic agent or a placebo, while maintaining a normal diet. 90 days later, those receiving the drug showed marked cognitive improvement compared to placebo, which was correlated with the level of ketones in the blood.
In a pilot study in 7 patients with Parkinson&rsquos disease, 5 were able to stick to the diet for 28 days and showed marked reduction in their physical symptoms. In an animal model of Amytrophic Lateral Sclerosis (ALS), a ketogenic diet also led to delayed motor neuron death and histological and functional improvements, although it did not increase life span clinical trials are on the way.
Remarkably, a long-term ketogenic diet does not seem to be associated with significant side effects, although constipation, dehydration and electrolyte and micronutrient deficiencies are common complaints. More serious complications include increased chance of kidney stones, gallbladder problems and bone fractures, especially in children. Menstrual irregularities often occur in women, with potential impact on fertlity. Although ketoacidosis &ndash acidification of the blood due to pathological levels of ketones &ndash was historically proposed as a side effect, nutritional ketosis simply cannot achieve the level of ketones required to induce this life-threatening state. Nevertheless, there are no studies directly monitoring the side effects of ketosis yet, hence it&rsquos too early to conclude that the diet is completely safe for everyone.
Brain <3 Bacon?
While promising, large-scale placebo-controlled clinical trials in patients with neurological disorders are still lacking. The existing data needs to be interpreted carefully to avoid generating false hope or encourage patients to &ldquoditch drugs for diet&ldquo. Nevertheless, the possibility that we can reduce symptoms of untreatable neurological disorders through modifying dietary composition is quite incredible that a ketogenic diet may benefit physical and cognitive performance in healthy individuals is an even more tantalizing idea.
As the science behind this age-old dietary therapy gradually comes to light, social issues such as low adherence and public prejudice will need to be resolved. In the meantime, to those neuroscientists interested in studying keto: pass the bacon and I VOLUNTEER!
Final note: Before I let you go, I&rsquod like to stress again that keto is NOT something to try out without talking to your doctor first, nor is it a replacement for pharmaceuticals. There&rsquos simply not enough evidence, on either its effectiveness or side effects. Nevertheless, it&rsquos a cool area of research to keep an eye on!
Related at Scientific American:
The views expressed are those of the author(s) and are not necessarily those of Scientific American.
ABOUT THE AUTHOR(S)
Shelly Xuelai Fan is a PhD Candidate in Neuroscience at the University of British Columbia, where she studies protein degradation in neurodegenerative diseases. She is an aspiring science writer with an insatiable obsession with the brain. She mulls over neuroscience, microbiomes and nutrition over at Neurorexia.
Chemical Reactions That Use Amino Acids
Carbohydrates & Respiration
Both methods of using amino acids for fuel involve a series of chemical reactions known as the Krebs cycle, a series of chemical reactions your body uses to generate energy. When blood glucose levels get very low, the body can use amino acids to make more glucose. This is necessary because some cells, such as neurons and red blood cells, can use only glucose for fuel. The glucogenic amino acids can be converted into large molecules that contain four or five carbon atoms that, when used as a substrate for the Krebs cycle, can be converted into glucose. Ketogenic amino acids form smaller molecules that, though unable to be turned into glucose, can still be used in the Krebs cycle for energy.
- Both methods of using amino acids for fuel involve a series of chemical reactions known as the Krebs cycle, a series of chemical reactions your body uses to generate energy.
- Ketogenic amino acids form smaller molecules that, though unable to be turned into glucose, can still be used in the Krebs cycle for energy.
Protein Building Blocks
Proteins are made of different amino acids, each of which has a different function in the body. One of the more important roles for amino acids is the manufacture of neurotransmitters, which affect your moods and the overall function of your nervous system. Getting amino acids across the BBB involves carrier molecules, which provide a transport vehicle for the amino acids. In addition, the carrier molecules must travel specific pathways through the BBB to get into the brain.
- Proteins are made of different amino acids, each of which has a different function in the body.
- One of the more important roles for amino acids is the manufacture of neurotransmitters, which affect your moods and the overall function of your nervous system.
Hypoglycemia is Brain Starvation
Given what you now know about your brain’s ability to use only glucose as fuel, when the concentration of glucose in your blood falls, your brain is one of the first organs to recognize the problem.
When threatened by low blood glucose, your brain is actually starved for fuel, resulting in confusion, lightheadedness, a loss of balance, slurred speech, and impaired vision. This state is called hypoglycemia, or low blood glucose.
Hypoglycemia can be very dangerous and sometimes fatal – when your brain is starved for glucose, your cognitive abilities rapidly decline, resulting in a system-wide panic.
That’s why it’s very important to ensure that you recognize the symptoms of hypoglycemia immediately, and consume carbohydrate-rich food to restore your brain function back to normal once again.
Best Carbohydrate Sources
The reason carbs have gotten a bad reputation is because many people associate them with starchy, refined carbohydrate-rich foods like white rice, pasta, white bread and sweets which aren’t particularly nutrient-rich. But there are plenty of good-for-you sources of carbohydrate – and they provide an abundance of vitamins, minerals, fiber and phytonutrients. So, if you follow a very low-carb diet, you may be missing these important nutrients which can help you stay healthy.
The healthiest sources of carbohydrates are foods that are generally the least processed (which means they retain their fiber and nutrients) — think fruit, vegetables, dairy, beans and whole grains. On the other hand, it’s best to limit your intake of highly processed carbs and sugars such as baked goods, soda, sugary treats, white rice, and white-flour cereals, pastas and crackers. These foods tend to spike your blood sugar levels, but don’t offer the “staying power” of the healthier carbs. And, they tend to lack the beneficial vitamins, minerals, phytonutrients and fiber, so they don’t offer a lot in the way of nutrition.
Sugar is a carbohydrate, and it’s wise to limit added sugars in the diet – like table sugar, honey, syrups and the like. But foods that naturally contain fruit are another story. When people decide to avoid eating fruit because they believe it to be “full of sugar”, they’re way off base. Fruit is one of the healthiest treats you can eat, and it contains a lot more than sugar.
To put it in perspective: A 50-calorie orange contains about 12 grams, or three teaspoons, of natural sugar, as well as three grams of fiber, 100% of the recommended daily amount of vitamin C, healthy antioxidants, folic acid and potassium. Compare that to a 225-calorie soda that contains 1/3 cup of sugar, and not much else – now that’s what I call “full of sugar”.
After the body metabolizes carbohydrates in your food, they enter the bloodstream in the form of glucose, or blood sugar, which provides energy to the cells. Glucose is also stashed away in your liver and muscles for later use, in a form called glycogen. Glycogen serves as a “reserve tank” for fuel – which is why your body might get that “running out of gas” feeling after prolonged activity, especially if you haven’t eaten enough carbs ahead of time.
Overview of Glucose Transport Regulation
Glucose transport is a highly regulated process that varies considerably from one cell type to another. Some cells, such as red blood cells and brain neurons, have obligate consumption of glucose. For other cells, a facultative use of glucose exists, permitting other metabolic fuels, such as fatty acids, to supply the bulk of local energy requirements. Much evidence suggests that the regulation of glucose transport is also isoform specific. Regulation of transport occurs in response to altered energy requirements of tissues, so it is not surprising that one form of cellular stress, energy lack, is a potent regulator of glucose transport and transporter expression by different tissues. Regulation of GLUT proteins may occur by variation of the amounts of synthesis or degradation of the GLUT protein or mRNA. An increased transcription of GLUT mRNA or other regulatory effects on GLUTs may occur as a result of stress hormones, such as glucocorticoids and epinephrine. In some tissues, these hormones have differing effects on expression of GLUTs or their transport activity, emphasizing their tissue-specific regulation. The effects of growth factors, physiological factors often involved in stress responses, increase GLUT1 transcription.
GLUT1 deficiency syndrome is caused by mutations in the SLC2A1 gene. This gene provides instructions for producing a protein called the glucose transporter protein type 1 (GLUT1). The GLUT1 protein is embedded in the outer membrane surrounding cells , where it transports a simple sugar called glucose into cells from the blood or from other cells for use as fuel.
In the brain, the GLUT1 protein is involved in moving glucose, which is the brain's main energy source, across the blood-brain barrier. The blood-brain barrier acts as a boundary between tiny blood vessels (capillaries ) and the surrounding brain tissue it protects the brain's delicate nerve tissue by preventing many other types of molecules from entering the brain. The GLUT1 protein also moves glucose between cells in the brain called glia, which protect and maintain nerve cells (neurons).
SLC2A1 gene mutations reduce or eliminate the function of the GLUT1 protein. Having less functional GLUT1 protein reduces the amount of glucose available to brain cells, which affects brain development and function.
Learn more about the gene associated with GLUT1 deficiency syndrome
How Statins Really Work Explains Why They Don't Really Work.
The statin industry has enjoyed a thirty year run of steadily increasing profits, as they find ever more ways to justify expanding the definition of the segment of the population that qualify for statin therapy. Large, placebo-controlled studies have provided evidence that statins can substantially reduce the incidence of heart attack. High serum cholesterol is indeed correlated with heart disease, and statins, by interfering with the body's ability to synthesize cholesterol, are extremely effective in lowering the numbers. Heart disease is the number one cause of death in the U.S. and, increasingly, worldwide. What's not to like about statin drugs?
I predict that the statin drug run is about to end, and it will be a hard landing. The thalidomide disaster of the 1950's and the hormone replacement therapy fiasco of the 1990's will pale by comparison to the dramatic rise and fall of the statin industry. I can see the tide slowly turning, and I believe it will eventually crescendo into a tidal wave, but misinformation is remarkably persistent, so it may take years.
I have spent much of my time in the last few years combing the research literature on metabolism, diabetes, heart disease, Alzheimer's, and statin drugs. Thus far, in addition to posting essays on the web, I have, together with collaborators, published two journal articles related to metabolism, diabetes, and heart disease (Seneff1 et al., 2011), and Alzheimer's disease (Seneff2 et al., 2011). Two more articles, concerning a crucial role for cholesterol sulfate in metabolism, are currently under review (Seneff3 et al., Seneff4 et al.). I have been driven by the need to understand how a drug that interferes with the synthesis of cholesterol, a nutrient that is essential to human life, could possibly have a positive impact on health. I have finally been rewarded with an explanation for an apparent positive benefit of statins that I can believe, but one that soundly refutes the idea that statins are protective. I will, in fact, make the bold claim that nobody qualifies for statin therapy, and that statin drugs can best be described as toxins.
2. Cholesterol and Statins
I would like to start by reexamining the claim that statins cut heart attack incidence by a third. What exactly does this mean? A meta study reviewing seven drug trials, involving in total 42,848 patients, ranging over a three to five year period, showed a 29% decreased risk of a major cardiac event (Thavendiranathan et al., 2006). But because heart attacks were rare among this group, what this translates to in absolute terms is that 60 patients would need to be treated for an average of 4.3 years to protect one of them from a single heart attack. However, essentially all of them will experience increased frailty and mental decline, a subject to which I will return in depth later on in this essay.
The impact of the damage due to the statin anti-cholesterol mythology extends far beyond those who actually consume the statin pills. Cholesterol has been demonized by the statin industry, and as a consequence Americans have become conditioned to avoid all foods containing cholesterol. This is a grave mistake, as it places a much bigger burden on the body to synthesize sufficient cholesterol to support the body's needs, and it deprives us of several essential nutrients. I am pained to watch someone crack open an egg and toss out the yolk because it contains "too much" cholesterol. Eggs are a very healthy food, but the yolk contains all the important nutrients. After all, the yolk is what allows the chick embryo to mature into a chicken. Americans are currently experiencing widespread deficiencies in several crucial nutrients that are abundant in foods that contain cholesterol, such as choline, zinc, niacin, vitamin A and vitamin D.
Cholesterol is a remarkable substance, without which all of us would die. There are three distinguishing factors which give animals an advantage over plants: a nervous system, mobility, and cholesterol. Cholesterol, absent from plants, is the key molecule that allows animals to have mobility and a nervous system. Cholesterol has unique chemical properties that are exploited in the lipid bilayers that surround all animal cells: as cholesterol concentrations are increased, membrane fluidity is decreased, up to a certain critical concentration, after which cholesterol starts to increase fluidity (Haines, 2001). Animal cells exploit this property to great advantage in orchestrating ion transport, which is essential for both mobility and nerve signal transport. Animal cell membranes are populated with a large number of specialized island regions appropriately called lipid rafts. Cholesterol gathers in high concentrations in lipid rafts, allowing ions to flow freely through these confined regions. Cholesterol serves a crucial role in the non-lipid raft regions as well, by preventing small charged ions, predominantly sodium (Na+) and potassium (K+), from leaking across cell membranes. In the absence of cholesterol, cells would have to expend a great deal more energy pulling these leaked ions back across the membrane against a concentration gradient.
In addition to this essential role in ion transport, cholesterol is the precursor to vitamin D3, the sex hormones, estrogen, progesterone, and testosterone, and the steroid hormones such as cortisol. Cholesterol is absolutely essential to the cell membranes of all of our cells, where it protects the cell not only from ion leaks but also from oxidation damage to membrane fats. While the brain contains only 2% of the body's weight, it houses 25% of the body's cholesterol. Cholesterol is vital to the brain for nerve signal transport at synapses and through the long axons that communicate from one side of the brain to the other. Cholesterol sulfate plays an important role in the metabolism of fats via bile acids, as well as in immune defenses against invasion by pathogenic organisms.
Statin drugs inhibit the action of an enzyme, HMG coenzyme A reductase, that catalyses an early step in the 25-step process that produces cholesterol. This step is also an early step in the synthesis of a number of other powerful biological substances that are involved in cellular regulation processes and antioxidant effects. One of these is coenzyme Q10, present in the greatest concentration in the heart, which plays an important role in mitochondrial energy production and acts as a potent antioxidant (Gottlieb et al., 2000). Statins also interfere with cell-signaling mechanisms mediated by so-called G-proteins, which orchestrate complex metabolic responses to stressed conditions. Another crucial substance whose synthesis is blocked is dolichol, which plays a crucial role in the endoplasmic reticulum. We can't begin to imagine what diverse effects all of this disruption, due to interference with HMG coenzyme A reductase, might have on the cell's ability to function.
3. LDL, HDL, and Fructose
We have been trained by our physicians to worry about elevated serum levels of low density lipoprotein (LDL), with respect to heart disease. LDL is not a type of cholesterol, but rather can be viewed as a container that transports fats, cholesterol, vitamin D, and fat-soluble anti-oxidants to all the tissues of the body. Because they are not water-soluble, these nutrients must be packaged up and transported inside LDL particles in the blood stream. If you interfere with the production of LDL, you will reduce the bioavailability of all these nutrients to your body's cells.
The outer shell of an LDL particle is made up mainly of lipoproteins and cholesterol. The lipoproteins contain proteins on the outside of the shell and lipids (fats) in the interior layer. If the outer shell is deficient in cholesterol, the fats in the lipoproteins become more vulnerable to attack by oxygen, ever-present in the blood stream. LDL particles also contain a special protein called "apoB" which enables LDL to deliver its goods to cells in need. ApoB is vulnerable to attack by glucose and other blood sugars, especially fructose. Diabetes results in an increased concentration of sugar in the blood, which further compromises the LDL particles, by gumming up apoB. Oxidized and glycated LDL particles become less efficient in delivering their contents to the cells. Thus, they stick around longer in the bloodstream, and the measured serum LDL level goes up.
Worse than that, once LDL particles have finally delivered their contents, they become "small dense LDL particles," remnants that would ordinarily be returned to the liver to be broken down and recycled. But the attached sugars interfere with this process as well, so the task of breaking them down is assumed instead by macrophages in the artery wall and elsewhere in the body, through a unique scavenger operation. The macrophages are especially skilled to extract cholesterol from damaged LDL particles and insert it into HDL particles. Small dense LDL particles become trapped in the artery wall so that the macrophages can salvage and recycle their contents, and this is the basic source of atherosclerosis. HDL particles are the so-called "good cholesterol," and the amount of cholesterol in HDL particles is the lipid metric with the strongest correlation with heart disease, where less cholesterol is associated with increased risk. So the macrophages in the plaque are actually performing a very useful role in increasing the amount of HDL cholesterol and reducing the amount of small dense LDL.
The LDL particles are produced by the liver, which synthesizes cholesterol to insert into their shells, as well as into their contents. The liver is also responsible for breaking down fructose and converting it into fat (Collison et al., 2009). Fructose is ten times more active than glucose at glycating proteins, and is therefore very dangerous in the blood serum (Seneff1 et al., 2011). When you eat a lot of fructose (such as the high fructose corn syrup present in lots of processed foods and carbonated beverages), the liver is burdened with getting the fructose out of the blood and converting it to fat, and it therefore can not keep up with cholesterol supply. As I said before, the fats can not be safely transported if there is not enough cholesterol. The liver has to ship out all that fat produced from the fructose, so it produces low quality LDL particles, containing insufficient protective cholesterol. So you end up with a really bad situation where the LDL particles are especially vulnerable to attack, and attacking sugars are readily available to do their damage.
4. How Statins Destroy Muscles
Europe, especially the U.K., has become much enamored of statins in recent years. The U.K. now has the dubious distinction of being the only country where statins can be purchased over-the-counter, and the amount of statin consumption there has increased more than 120% in recent years (Walley et al, 2005). Increasingly, orthopedic clinics are seeing patients whose problems turn out to be solvable by simply terminating statin therapy, as evidenced by a recent report of three cases within a single year in one clinic, all of whom had normal creatine kinase levels, the usual indicator of muscle damage monitored with statin usage, and all of whom were "cured" by simply stopping statin therapy (Shyam Kumar et al., 2008). In fact, creatine kinase monitoring is not sufficient to assure that statins are not damaging your muscles (Phillips et al., 2002).
Since the liver synthesizes much of the cholesterol supply to the cells, statin therapy greatly impacts the liver, resulting in a sharp reduction in the amount of cholesterol it can synthesize. A direct consequence is that the liver is severely impaired in its ability to convert fructose to fat, because it has no way to safely package up the fat for transport without cholesterol (Vila et al., 2011). Fructose builds up in the blood stream, causing lots of damage to serum proteins.
The skeletal muscle cells are severely affected by statin therapy. Four complications they now face are: (1) their mitochondria are inefficient due to insufficient coenzyme Q10, (2) their cell walls are more vulnerable to oxidation and glycation damage due to increased fructose concentrations in the blood, reduced cholesterol in their membranes, and reduced antioxidant supply, (3) there's a reduced supply of fats as fuel because of the reduction in LDL particles, and (4) crucial ions like sodium and potassium are leaking across their membranes, reducing their charge gradient. Furthermore, glucose entry, mediated by insulin, is constrained to take place at those lipid rafts that are concentrated in cholesterol. Because of the depleted cholesterol supply, there are fewer lipid rafts, and this interferes with glucose uptake. Glucose and fats are the main sources of energy for muscles, and both are compromised.
As I mentioned earlier, statins interfere with the synthesis of coenzyme Q10 (Langsjoen and Langsjoen, 2003), which is highly concentrated in the heart as well as the skeletal muscles, and, in fact, in all cells that have a high metabolic rate. It plays an essential role in the citric acid cycle in mitochondria, responsible for the supply of much of the cell's energy needs. Carbohydrates and fats are broken down in the presence of oxygen to produce water and carbon dioxide as by-products. The energy currency produced is adenosine triphosphate (ATP), and it becomes severely depleted in the muscle cells as a consequence of the reduced supply of coenzyme Q10.
The muscle cells have a potential way out, using an alternative fuel source, which doesn't involve the mitochondria, doesn't require oxygen, and doesn't require insulin. What it requires is an abundance of fructose in the blood, and fortunately (or unfortunately, depending on your point of view) the liver's statin-induced impairment results in an abundance of serum fructose. Through an anaerobic process taking place in the cytoplasm, specialized muscle fibers skim off just a bit of the energy available from fructose, and produce lactate as a product, releasing it back into the blood stream. They have to process a huge amount of fructose to produce enough energy for their own use. Indeed, statin therapy has been shown to increase the production of lactate by skeletal muscles (Pinieux et al, 1996).
Converting one fructose molecule to lactate yields only two ATP's, whereas processing a sugar molecule all the way to carbon dioxide and water in the mitochondria yields 38 ATP's. In other words, you need 19 times as much substrate to obtain an equivalent amount of energy. The lactate that builds up in the blood stream is a boon to both the heart and the liver, because they can use it as a substitute fuel source, a much safer option than glucose or fructose. Lactate is actually an extremely healthy fuel, water-soluble like a sugar but not a glycating agent.
So the burden of processing excess fructose is shifted from the liver to the muscle cells, and the heart is supplied with plenty of lactate, a high-quality fuel that does not lead to destructive glycation damage. LDL levels fall, because the liver can't keep up with fructose removal, but the supply of lactate, a fuel that can travel freely in the blood (does not have to be packaged up inside LDL particles) saves the day for the heart, which would otherwise feast off of the fats provided by the LDL particles. I think this is the crucial effect of statin therapy that leads to a reduction in heart attack risk: the heart is well supplied with a healthy alternative fuel.
This is all well and good, except that the muscle cells get wrecked in the process. Their cell walls are depleted in cholesterol because cholesterol is in such short supply, and their delicate fats are therefore vulnerable to oxidation damage. This problem is further compounded by the reduction in coenzyme Q10, a potent antioxidant. The muscle cells are energy starved, due to dysfunctional mitochondria, and they try to compensate by processing an excessive amount of both fructose and glucose anaerobically, which causes extensive glycation damage to their crucial proteins. Their membranes are leaking ions, which interferes with their ability to contract, hindering movement. They are essentially heroic sacrificial lambs, willing to die in order to safeguard the heart.
Muscle pain and weakness are widely acknowledged, even by the statin industry, as potential side effects of statin drugs. Together with a couple of MIT students, I have been conducting a study which shows just how devastating statins can be to muscles and the nerves that supply them (Liu et al, 2011). We gathered over 8400 on-line drug reviews prepared by patients on statin therapy, and compared them to an equivalent number of reviews for a broad spectrum of other drugs. The reviews for comparison were selected such that the age distribution of the reviewers was matched against that for the statin reviews. We used a measure which computes how likely it would be for the words/phrases that show up in the two sets of reviews to be distributed in the way they are observed to be distributed, if both sets came from the same probability model. For example, if a given side effect showed up a hundred times in one data set and only once in the other, this would be compelling evidence that this side effect was representative of that data set. Table 1 shows several conditions associated with muscle problems that were highly skewed towards the statin reviews.
|Side Effect||# Statin Reviews||# Non-Statin Reviews||Associated P-value|
|Loss of Muscle Mass||54||5||0.01323|
I believe that the real reason why statins protect the heart from a heart attack is that muscle cells are willing to make an incredible sacrifice for the sake of the larger good. It is well acknowledged that exercise is good for the heart, although people with a heart condition have to watch out for overdoing it, walking a careful line between working out the muscles and overtaxing their weakened heart. I believe, in fact, that the reason exercise is good is exactly the same as the reason statins are good: it supplies the heart with lactate, a very healthy fuel that does not glycate cell proteins.
5. Membrane Cholesterol Depletion and Ion Transport
As I alluded to earlier, statin drugs interfere with the ability of muscles to contract through the depletion of membrane cholesterol. (Haines, 2001) has argued that the most important role of cholesterol in cell membranes is the inhibition of leaks of small ions, most notably sodium (Na+) and potassium (K+). These two ions are essential for movements, and indeed, cholesterol, which is absent in plants, is the key molecule that permits mobility in animals, through its strong control over ion leakage of these molecules across cell walls. By protecting the cell from ion leaks, cholesterol greatly reduces the amount of energy the cell needs to invest in keeping the ions on the right side of the membrane.
There is a widespread misconception that "lactic acidosis," a condition that can arise when muscles are worked to exhaustion, is due to lactic acid synthesis. The actual story is the exact opposite: the acid build-up is due to excess breakdown of ATP to ADP to produce energy to support muscle contraction. When the mitochondria can't keep up with energy consumption by renewing the ATP, the production of lactate becomes absolutely necessary to prevent acidosis (Robergs et al., 2004). In the case of statin therapy, excessive leaks due to insufficient membrane cholesterol require more energy to correct, and all the while the mitochondria are producing less energy.
In in vitro studies of phospholipid membranes, it has been shown that the removal of cholesterol from the membrane leads to a nineteen fold increase in the rate of potassium leaks through the membrane (Haines, 2001). Sodium is affected to a lesser degree, but still by a factor of three. Through ATP-gated potassium and sodium channels, cells maintain a strong disequilibrium across their cell wall for these two ions, with sodium being kept out and potassium being held inside. This ion gradient is what energizes muscle movement. When the membrane is depleted in cholesterol, the cell has to burn up substantially more ATP to fight against the steady leakage of both ions. With cholesterol depletion due to statins, this is energy it doesn't have, because the mitochondria are impaired in energy generation due to coenzyme-Q10 depletion.
Muscle contraction itself causes potassium loss, which further compounds the leak problem introduced by the statins, and the potassium loss due to contraction contributes significantly to muscle fatigue. Of course, muscles with insufficient cholesterol in their membranes lose potassium even faster. Statins make the muscles much more vulnerable to acidosis, both because their mitochondria are dysfunctional and because of an increase in ion leaks across their membranes. This is likely why athletes are more susceptible to muscle damage from statins (Meador and Huey, 2010, Sinzinger and O'Grady, 2004): their muscles are doubly challenged by both the statin drug and the exercise.
An experiment with rat soleus muscles in vitro showed that lactate added to the medium was able to almost fully recover the force lost due to potassium loss (Nielsen et al, 2001). Thus, production and release of lactate becomes essential when potassium is lost to the medium. The loss of strength in muscles supporting joints can lead to sudden uncoordinated movements, overstressing the joints and causing arthritis (Brandt et al., 2009). In fact, our studies on statin side effects revealed a very strong correlation with arthritis, as shown in the table.
While I am unaware of a study involving muscle cell ion leaks and statins, a study on red blood cells and platelets has shown that there is a substantial increase in the Na+-K+-pump activity after just a month on a modest 10 mg/dl statin dosage, with a concurrent decrease in the amount of cholesterol in the membranes of these cells (Lohn et al., 2000). This increased pump activity (necessitated by membrane leaks) would require additional ATP and thus consume extra energy.
Muscle fibers are characterized along a spectrum by the degree to which they utilize aerobic vs anaerobic metabolism. The muscle fibers that are most strongly damaged by statins are the ones that specialize in anaerobic metabolism (Westwood et al., 2005). These fibers (Type IIb) have very few mitochondria, as contrasted with the abundant supply of mitochondria in the fully aerobic Type 1A fibers. I suspect their vulnerability is due to the fact that they carry a much larger burden of generating ATP to fuel the muscle contraction and to produce an abundance of lactate, a product of anaerobic metabolism. They are tasked with both energizing not only themselves but also the defective aerobic fibers (due to mitochondrial dysfunction) and producing enough lactate to offset the acidosis developing as a consequence of widespread ATP shortages.
6. Long-term Statin Therapy Leads to Damage Everywhere
Statins, then, slowly erode the muscle cells over time. After several years have passed, the muscles reach a point where they can no longer keep up with essentially running a marathon day in and day out. The muscles start literally falling apart, and the debris ends up in the kidney, where it can lead to the rare disorder, rhabdomyolysis, which is often fatal. In fact, 31 of our statin reviews contained references to "rhabdomyolysis" as opposed to none in the comparison set. Kidney failure, a frequent consequence of rhabdomyolysis, showed up 26 times among the statin reviews, as opposed to only four times in the control set.
The dying muscles ultimately expose the nerves that innervate them to toxic substances, which then leads to nerve damage such as neuropathy, and, ultimately Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease, a very rare, debilitating, and ultimately fatal disease which is now on the rise due (I believe) to statin drugs. People diagnosed with ALS rarely live beyond five years. Seventy-seven of our statin reviews contained references to ALS, as against only 7 in the comparison set.
As ion leaks become untenable, cells will begin to replace the potassium/sodium system with a calcium/magnesium based system. These two ions are in the same rows of the periodic table as sodium/potassium, but advanced by one column, which means that they are substantially larger, and therefore it's much harder for them to accidentally leak out. But this results in extensive calcification of artery walls, heart valves, and the heart muscle itself. Calcified heart valves can no longer function properly to prevent backflow, and diastolic heart failure results from increased left ventricular stiffness. Research has shown that statin therapy leads to increased risk to diastolic heart failure (Silver et al., 2004, Weant and Smith, 2005). Heart failure shows up 36 times in our statin drug data as against only 8 times in the comparison group.
Once the muscles can no longer keep up with lactate supply, the liver and heart will be further imperilled. They're now worse off than they were before statins, because the lactate is no longer available, and the LDL, which would have provided fats as a fuel source, is greatly reduced. So they're stuck processing sugar as fuel, something that is now much more perilous than it used to be, because they are depleted in membrane cholesterol. Glucose entry into muscle cells, including the heart muscle, mediated by insulin, is orchestrated to occur at lipid rafts, where cholesterol is highly concentrated. Less membrane cholesterol results in fewer lipid rafts, and this leads to impaired glucose uptake. Indeed, it has been proposed that statins increase the risk to diabetes (Goldstein and Mascitelli, 2010, Hagedorn and Arora, 2010). Our data bear out this notion, with the probability of the observed distributions of diabetes references happening by chance being only 0.006.
|Side Effect||# Statin Reviews||# Non-Statin Reviews||Associated P-value|
7. Statins, Caveolin, and Muscular Dystrophy
Lipid rafts are crucial centers for transport of substances (both nutrients and ions) across cell membranes and as a cell signaling domain in essentially all mammalian cells. Caveolae ("little caves") are microdomains within lipid rafts, which are enriched in a substance called caveolin (Gratton et al., 2004). Caveolin has received increasing attention of late due to the widespread role it plays in cell signaling mechanisms and the transport of materials between the cell and the environment (Smart et al., 1999).
Statins are known to interfere with caveolin production, both in endothelial cells (Feron et al., 2001) and in heart muscle cells, where they've been shown to reduce the density of caveolae by 30% (Calaghan, 2010). People who have a defective form of caveolin-3, the version of caveolin that is present in heart and skeletal muscle cells, develop muscular dystrophy as a consequence (Minetti et al., 1998). Mice engineered to have defective caveolin-3 that stayed in the cytoplasm instead of binding to the cell wall at lipid rafts exhibited stunted growth and paralysis of their legs (Sunada et al., 2001). Caveolin is crucial to cardiac ion channel function, which, in turn, is essential in regulating the heart beat and protecting the heart from arrhythmias and cardiac arrest (Maguy et al, 2006). In arterial smooth muscle cells, caveolin is essential to the generation of calcium sparks and waves, which, in turn, are essential for arterial contraction and expansion, to pump blood through the body (Taggart et al, 2010).
In experiments involving constricting the arterial blood supply to rats' hearts, researchers demonstrated a 34% increase in the amount of caveolin-3 produced by the rat's hearts, along with a 27% increase in the weight of the left ventricle, indicating ventricular hypertrophy. What this implies is that the heart needs additional caveolin to cope with blocked vessels, whereas statins interfere with the ability to produce extra caveolin (Kikuchi et al., 2005).
8. Statins and the Brain
While the brain is not the focus of this essay, I cannot resist mentioning the importance of cholesterol to the brain and the evidence of mental impairment available from our data sets. Statins would be expected to have a negative impact on the brain, because, while the brain makes up only 2% of the body's weight, it houses 25% of the body's cholesterol. Cholesterol is highly concentrated in the myelin sheath, which encloses axons which transport messages long distances (Saher et al., 2005). Cholesterol also plays a crucial role in the transmission of neurotransmitters across the synapse (Tong et al, 2009). We found highly skewed distribution of word frequencies for dementia, Parkinson's disease, and short term memory loss, with all of these occurring much more frequently in the statin reviews than in the comparison reviews.
A recent evidence-based article (Cable, 2009) found that statin drug users had a high incidence of neurological disorders, especially neuropathy, parasthesia and neuralgia, and appeared to be at higher risk to the debilitating neurological diseases, ALS and Parkinson's disease. The evidence was based on careful manual labeling of a set of self-reported accounts from 351 patients. A mechanism for such damage could involve interference with the ability of oligodendrocytes, specialized glial cells in the nervous system, to supply sufficient cholesterol to the myelin sheath surrounding nerve axons. Genetically-engineered mice with defective oligodendrocytes exhibit visible pathologies in the myelin sheath which manifest as muscle twitches and tremors (Saher et al, 2005). Cognitive impairment, memory loss, mental confusion, and depression were also significantly present in Cable’s patient population. Thus, his analysis of 351 adverse drug reports was largely consistent with our analysis of 8400 reports.
9. Cholesterol's Benefits to Longevity
The broad spectrum of severe disabilities with increased prevalence in statin side effect reviews all point toward a general trend of increased frailty and mental decline with long-term statin therapy, things that are usually associated with old age. I would in fact best characterize statin therapy as a mechanism to allow you to grow old faster. A highly enlightening study involved a population of elderly people who were monitored over a 17 year period, beginning in 1990 (Tilvis et al., 2011). The investigators looked at an association between three different measures of cholesterol and manifestations of decline. They measured indicators associated with physical frailty and mental decline, and also looked at overall longevity. In addition to serum cholesterol, a biometric associated with the ability to synthesize cholesterol (lathosterol) and a biometric associated with the ability to absorb cholesterol through the gut (sitosterol) were measured.
Low values of all three measures of cholesterol were associated with a poorer prognosis for frailty, mental decline and early death. A reduced ability to synthesize cholesterol showed the strongest correlation with poor outcome. Individuals with high measures of all three biometrics enjoyed a 4.3 year extension in life span, compared to those for whom all measures were low. Since statins specifically interfere with the ability to synthesize cholesterol, it is logical that they would also lead to increased frailty, accelerated mental decline, and early death.
For both ALS and heart failure, survival benefit is associated with elevated cholesterol levels. A statistically significant inverse correlation was found in a study on mortality in heart failure. For 181 patients with heart disease and heart failure, half of those whose serum cholesterol was below 200 mg/dl were dead three years after diagnosis, whereas only 28% of the patients whose serum cholesterol was above 200 mg/dl had died. In another study on a group of 488 patients diagnosed with ALS, serum levels of triglycerides and fasting cholesterol were measured at the time of diagnosis (Dorstand et al., 2010). High values for both lipids were associated with improved survival, with a p-value How Statins Really Work Explains Why They Don't Really Work. by Stephanie Seneff is licensed under a Creative Commons Attribution 3.0 United States License.
Hormones Involved in Blood Glucose Regulation
Central to maintaining blood glucose homeostasis are two hormones, insulin and glucagon, both produced by the pancreas and released into the bloodstream in response to changes in blood glucose.
Insulin is made by the beta-cells of the pancreas and released when blood glucose is high. It causes cells around the body to take up glucose from the blood, resulting in lowering blood glucose concentrations.
Glucagon is made by the alpha-cells of the pancreas and released when blood glucose is low. It causes glycogen in the liver to break down, releasing glucose into the blood, resulting in raising blood glucose concentrations. (Remember that glycogen is the storage form of glucose in animals.)
The image below depicts a mouse islet of Langerhans, a cluster of endocrine cells in the pancreas. The beta-cells of the islet produce insulin, and the alpha-cells produce glucagon.
Fig. 5.1. A mouse islet of Langerhans, visualized with immunofluorescent microscopy. In this image, cell nuclei are stained blue, insulin is stained red, and blood vessels are stained green. You can see that this islet is packed with insulin and sits right next to a blood vessel, so that it can secrete the two hormones, insulin and glucagon, into the blood. Glucagon is not stained in this image, but it's there!
In the figure below, you can see blood glucose and insulin throughout a 24-hour period, including three meals. You can see that when glucose rises, it is followed immediately by a rise in insulin, and glucose soon drops again. The figure also shows the difference between consuming a sucrose-rich food and a starch-rich food. The sucrose-rich food results in a greater spike in both glucose and insulin. Because more insulin is required to handle that spike, it also causes a more precipitous decline in blood glucose. This is why eating a lot of sugar all at once may increase energy in the short-term, but soon after may make you feel like taking a nap!
Fig. 5.2. Typical pattern of blood glucose and insulin during a 24-hour period, showing peaks for each of 3 meals and highlighting the effects of consumption of sugar-rich foods.
Let's look a little closer at how insulin works, illustrated in the figure below. Insulin is released by the pancreas into the bloodstream. Cells around the body have receptors for insulin on their cell membranes. Insulin fits into its receptors (labeled as step 1 in the figure), kind of like a key in a lock, and through a series of reactions (step 2), triggers glucose transporters to open on the surface of the cell (step 3). Now glucose can enter the cell, making it available for the cell to use and at the same time lowering the concentration of glucose in the blood.
Fig. 5.3. Insulin binds to its receptors on the cell membrane, triggering GLUT-4 glucose transporters to open on the membrane. This allows glucose to enter the cell, where it can be used in several ways.
The figure also shows several different ways glucose can be used once it enters the cell.
If the cell needs energy right away, it can metabolize glucose through cellular respiration, producing ATP (step 5).
If the cell doesn't need energy right away, glucose can be converted to other forms for storage. If it's a liver or muscle cell, it can be converted to glycogen (step 4). Alternatively, it can be converted to fat and stored in that form (step 6).
In addition to its role in glucose uptake into cells, insulin also stimulates glycogen and fat synthesis as described above. It also stimulates protein synthesis. You can think of its role as signaling to the body that there's lots of energy around, and it's time to use it and store it in other forms.
On the other hand, when blood glucose falls, several things happen to restore homeostasis.
You receive messages from your brain and nervous system that you should eat. If that doesn't work, or doesn't work fast enough….
Glucagon is released from the pancreas into the bloodstream. In liver cells, it stimulates the breakdown of glycogen, releasing glucose into the blood.
In addition, glucagon stimulates a process called gluconeogenesis, in which new glucose is made from amino acids (building blocks of protein) in the liver and kidneys, also contributing to raising blood glucose.
Proven ways to protect your brain
A paradigm shift is happening in terms of how neuroscientists and doctors are thinking about women&rsquos brain health, says Brinton. Rather than treating symptoms when we&rsquore older and cognitively too far gone, we need to take brain-health boosting steps now. In fact, recent population-based studies estimate that over a third of all Alzheimer&rsquos cases could be prevented if people made key lifestyle shifts. Here&rsquos what you can do in your 40s, 50s, and beyond to make your brain more resilient. The best part: It&rsquos never too late to start.
Don&rsquot ignore brain blips.
Brain fog and forgetfulness may seem like normal parts of perimenopause, but they&rsquore actually important clues that estrogen changes are happening in your brain, says Brinton. &ldquoThese are signs that you have a window of opportunity to implement strategies that can prevent risks.&rdquo
For example, you may be a good candidate for hormone replacement therapy (HRT). &ldquoOur research shows that if hormone therapy is prescribed when women have menopausal symptoms, it can reduce the risk of developing Alzheimer&rsquos,&rdquo says Brinton. &ldquoWhen HRT is introduced after menopause, when the brain&rsquos estrogen response system has already been dismantled, HRT is of no benefit.&rdquo
Chow down the brain-healthy way.
If you&rsquore looking for a science-backed diet for your brain&rsquos health, loading up on veggies, herbs, fish, fruits, nuts, beans, and whole grains&mdashthe Mediterranean diet&mdashis the way to go, says Mosconi. Her research found that brains of 50-year-old women following this diet looked five years younger than those of same-age women who ate a typical Western diet. The plant-based foods are rich in phytoestrogens, which act like mild estrogen in the body.
It&rsquos also important to get enough fiber, she says. &ldquoFiber influences levels of sex hormone binding globulin [SHBG], which greatly impacts estrogen,&rdquo says Mosconi. &ldquoFibrous veggies are a great way to get your brain the glucose it needs, because fiber stabilizes your blood sugar, which allows the glucose to reach your brain.&rdquo Veggies with the highest concentration of glucose and fiber include scallions, spring onions, turnips, rutabagas, carrots, parsnips, and red beets.
Move your body.
Exercise is one of the strongest preventive tools against Alzheimer&rsquos disease for everyone, but it seems to be especially important for women: In females younger than 65, physical activity is associated with a 30% lower risk of Alzheimer&rsquos compared with those who are sedentary, and women age 65 to 70 who exercise see a 20% risk reduction.
Not a big fan of the gym? Says Brinton: &ldquoJust try to sneak in more movement throughout your day.&rdquo She has an inexpensive stair stepper next to her desk and uses it for a few minutes every hour. &ldquoIf you love higher-intensity workouts, go for it,&rdquo says Brinton. &ldquoBut know that even little bouts of lower-intensity movement throughout the day will get your heart rate up and increase blood flow to your brain, which helps to keep it healthy.&rdquo
Rest your body and mind.
Research shows that women have a harder time falling asleep and staying asleep than men do, which is a shame, because sleep is what Brinton calls the great brain elixir. &ldquoAs you get older, you have to build in additional repair and recovery time, which happens while you sleep,&rdquo she says.
So follow the good advice you&rsquove heard before: Limit screen time at night, establish a relaxing bedtime routine, spend time in natural light to regulate your circadian rhythm, and avoid daytime naps. And get professional help if you are having trouble sleeping or don&rsquot feel rested when you wake up, says Brinton.
Lighten your mental load.
Female neuroscientists have just started to study the concept of &ldquocognitive load&rdquo (a.k.a. the amount of mental gymnastics most women do on a daily basis to keep all the balls in the air) and its impact on our brains. It turns out that doing most of the planning work in the household&mdashmaking doctor&rsquos appointments, booking the family vacation, and the list goes on&mdashcan mean cognitive problems later in life.
&ldquoHaving some mental load is a good thing,&rdquo says Caldwell, but when this added responsibility gets overwhelming, &ldquoyou&rsquove got a potentially chronic stressor that&rsquos really bad for your brain.&rdquo Be honest about what you can juggle&mdashand what feels like too much. Then take some things off your list. Says Caldwell: &ldquoIf you had a friend with your level of load, what would you tell her?&rdquo
After all, you deserve to focus on your brain health. As Brinton says, &ldquoThe neural circuitry in your brain makes up who you are&mdashwhich means taking care of your brain is crucial if you want to take care of yourself.&rdquo Protecting your noggin is the ultimate form of self-care. So do that for yourself, as Brinton and her colleagues search for solutions for all.
This article originally appeared in the June 2021 issue of Prevention.