Summary: Accumulation of amyloid-beta appears to play a central role in the development of Alzheimer’s. However, researchers have a limited understanding of the production of amyloid protein in brain cells. But new studies show that the production of amyloid-beta protein is increased in those with higher cholesterol synthesis by astrocytes (supporting cells in the brain) and its transportation with the help of apoE protein. It means that regulating the production and transportation of cholesterol by astrocytes may help prevent amyloid-beta overproduction and plaque formation. Thus, it could be a way to prevent Alzheimer’s or slow down its progress.
It could also mean that the accumulation of amyloid-beta could be a surrogate marker of disease, with accumulation due to localized inflammation and lack of clearance.
Keywords: amyloid-beta, brain, Alzheimer’s, astrocytes, cholesterol, apoE
However, researchers are not sure why this accumulation of amyloid and tau plaques occurs. They are unsure if the formation of these plaques is the leading cause of Alzheimer’s or formation of these plaques happens as a result of something else. Demystifying this puzzle may help find the treatment of the condition.
Researchers know that many metabolic disorders result from changes in lifestyle that occurred in the last century or so. They also know that it has led to the dysregulation of cholesterol metabolism, causing a higher prevalence of heart diseases and stroke. However, now a new study shows that cholesterol may play a role in Alzheimer’s, too.
Researchers have also studied the role of the most abundant cells in the brain: astrocytes. They almost tile the whole brain and are about five times more than neurons. They are needed for the working of brain cells neurons. They provide brain cells with vital support. Nonetheless, when we talk about the brain, we often forget about them, only considering neurons1.
It is known that the brain requires lots of cholesterol, as a considerable part of the brain is made of cholesterol. However, as people grow older, neurons start losing their ability to produce cholesterol. Thus, in adults, most of the cholesterol is produced by astrocytes. These brain cells then transport the cholesterol to neurons with the help of a protein called apolipoprotein E (apoE).
Early studies showed that those with apoE defects due to genetic reasons have a higher rate of Alzheimer’s. But researchers did not know why a defect in apoE, the transporter protein, increases the risk of Alzheimer’s2.
The researcher found that increased apoE resulted in increased cholesterol transportation to the neurons in the new finding. Cholesterol is needed by brain cells to produce amyloid protein. However, a high supply of cholesterol may also result in the overproduction of amyloid protein, resulting in the formation of amyloid plaques. It means that astrocytes and their greater supply of cholesterol to neurons may result in the formation and growth of amyloid plaques, thus causing Alzheimer’s.
Studies show that cholesterol levels are high in the brain of those living with Alzheimer’s. It means that suppression of cholesterol production by astrocytes may also help lower the production of amyloid protein. Further, it may be good to suppress apoE, the major transportation protein for cholesterol, to prevent amyloid plaque formation.
In the experimental study, researchers found that reducing the activity of transporter protein apoE resulted in less supply of cholesterol and thus lesser formation of amyloid plaques.
Thus, researchers think that astrocytes and their increased production and transportation of cholesterol to neurons may be causing amyloid-beta accumulation and Alzheimer’s. Tests in animal models show that suppressing the ability of astrocytes to produce cholesterol in the brain or reducing their ability to transport cholesterol may help prevent Alzheimer’s3.
Further, researchers think that reducing the overproduction of cholesterol may be the right way of preventing Alzheimer’s. Although amyloid-beta accumulation ultimately causes Alzheimer’s, suppressing its production is not an option. The brain tightly controls the production of amyloid protein due to its high importance in brain health. It means suppressive amyloid production directly may have unforeseeable results. Moreover, researchers do not have much understanding of how amyloid protein is produced in brain cells. It could also simply be that cholesterol over production is a reactive phenomenon due to underlying metabolic inflammation, and that the amyloid-beta protein tangles accumulate because the clearance mechanism is inhibited.
To conclude, controlling the production and transportation of cholesterol by astrocytes may be a key to preventing Alzheimer’s or slowing down its progress.
References
1. Sofroniew MV, Vinters HV. Astrocytes: biology and pathology. Acta Neuropathol. 2010;119(1):7-35. doi:10.1007/s00401-009-0619-8
2. Yamazaki Y, Painter MM, Bu G, Kanekiyo T. Apolipoprotein E as a Therapeutic Target in Alzheimer’s disease: A Review of Basic Research and Clinical Evidence. CNS Drugs. 2016;30(9):773-789. doi:10.1007/s40263-016-0361-4
3. Wang H, Kulas JA, Wang C, Holtzman DM, Ferris HA, Hansen SB. Regulation of beta-amyloid production in neurons by astrocyte-derived cholesterol. PNAS. 2021;118(33). doi:10.1073/pnas.2102191118
A calorie in physics is the energy required to raise the temperature of 1 gram of water 1 °C.
The calorie you see on a food package is actually a kilocalorie, or 1,000 calories, the amount of energy needed to raise the temperature of 1 kilogram of water 1 degree Celsius.
The original method used to determine calories in a given food directly measured the energy it produced. The food was placed in a sealed container surrounded by water, a bomb calorimeter. The food was completely burned and the resulting rise in water temperature was measured.
Full-fat dairy may protect against obesity. A 2014 study concluded: “Participants in the highest tertile of whole-fat dairy intakes (milk, cheese, yogurt) had significantly lower odds for being obese.”
Full-fat dairy may protect against obesity. A 2014 study concluded: “Participants in the highest tertile of whole-fat dairy intakes (milk, cheese, yogurt) had significantly lower odds for being obese.”
Important Points:
- whole grains
- refined grains
- Western dietary pattern
- diabetes
- obesity
Refined Grains: The Good, the Bad, the Ugly
Flour is all around us and a temptation at every meal. Breakfast toast, bagels, cereal, and pancakes fill our tables. Lunch revolves around sandwiches, wraps, pasta and pizza. Refined grains have been vilified as one of the leadings causes of ill health. Is there any truth to this? Should we toss all refined grain products off our tables? We will have an in-depth look at the good, the bad, and the ugly of refined flour to give you a better understanding of the goodies on your plate.
What are Refined Grains?
Refined grain is the term used to refer to grains that are not whole, because they are missing one or more of their three key parts (bran, germ, or endosperm). White flour and white rice are refined grains, for instance, because both have had their bran and germ removed, leaving only the endosperm. Refining a grain removes about a quarter of the protein in a grain and half to two thirds or more of a score of nutrients, leaving the grain a mere shadow of its original self.
Further refining includes mixing, bleaching, and brominating; additionally, thiamin, riboflavin, niacin, and iron are often added back in to nutritionally enrich the product. Because the added nutrients represent a fraction of the nutrients removed, refined grains are considered nutritionally inferior to whole grains. However, for some grains the removal of fiber coupled with fine grinding results in a slightly higher availability of grain energy for use by the body.
Grain refining led to disastrous and widespread nutritional problems, like the deficiency diseases pelagra and beri-beri. In response, many governments recommended or required that refined grains be “enriched.”
The Good
The federal government’s 2010 Dietary Guidelines for Americans recommend that half your daily grain intake be from high-fiber whole-grain sources, foods like brown rice, oatmeal and whole-wheat bread. Nutritionists often exhort people to choose whole grains over refined ones whenever they can.
But according to one leading nutrition researcher, Julie Miller Jones, a professor emeritus at St. Catherine University, we shouldn’t be so eager to throw out refined grains altogether. Refined grains do have some benefits — namely, nutrients added to refined flours.
Since folic acid was added to bread, cereal and other grains in 1999, the rate of newborns with neural tube defects — a known consequence of folic acid deficiency — has decreased 46%. Additionally, important nutrients like copper and iron are more easily absorbed when eaten with refined grains. Whole grains are healthy because they’re so high in fiber, which Americans don’t get enough of, but that fiber also fast-tracks food through the digestive system, absorbing nutrients along the way.
The Bad
As our national appetite for flour has inched up, so has the incidence of diet-related ills, such as obesity, heart disease and diabetes. Coincidence? Many nutrition experts don’t think so. When they weigh the evidence linking food choices and disease, they see the white, dusty fingerprints of flour everywhere.
Flour started out as an ingenious fix to a vexing problem. Grass seeds were plentiful, but the tough outer shell (the husk) made the seeds difficult to chew and digest. Early humans outsmarted the seeds by grinding them between stones, crushing the outer layers to get at the goodness inside. The result — a coarse powder — was the first whole-grain flour.
The downside was spoilage. Crushing the germ released its oils, which quickly turned rancid when exposed to air. With the advent of industrial milling in the late 1800s, machines began filtering out the germ and pulverized the remaining endosperm into a fine, white powder that lasted on the shelf for months. And so all-purpose white flour was born — along with a host of health problems.
Beneath their rigid architecture, whole-kernel grains conceal an array of vitamins, minerals, phytonutrients and fiber. But when machines pulverize kernels into flour, even whole-grain flour, what’s left behind is a starchy powder capable of wreaking havoc on the body.
The Ugly
Overconsuming flour can lead to a number of problems in the body, including:
- Food Allergies/Intolerances. Gluten intolerance is a term that has become synonymous with the current generation. Wheat is one of the biggest dietary triggers of food allergies and intolerances. While the exact reason is unclear, many experts blame the higher gluten content of modern wheat varieties
- Blood-Sugar Spikes. The difference between a whole-kernel grain and a processed grain all boils down to the glycemic index, which is how quickly the body turns food into fuel, or glucose. Foods made with wheat flour are particularly damaging. A carbohydrate in wheat, called amylopectin A, is more easily converted to blood sugar than just about any other carbohydrate. Two slices of bread made with whole-wheat flour raise blood sugar higher than six teaspoons of table sugar and higher than many candy bars.
- Food Cravings. One of the biggest changes in modern wheat is that it contains a modified form of gliadin, a protein found in wheat gluten. Gliadin releases a feel-good effect in the brain by morphing into a substance that crosses the blood-brain barrier and binds onto the brain’s opiate receptors and makes you want to eat more.
- Caloric Overload. A refined grain packs more calories than a whole-kernel grain because it is more concentrated, and foods that are high in grains also tend to be high in sugar and industrialized fats. These foods contribute largely to obesity and the diabetes epidemic.
- Metabolic Slowdown. Research shows that the body may shift nutrients into fat storage and away from muscle burning in the presence of high-glycemic-index foods. In 2004, Ludwig and his colleagues at Harvard conducted a study, published in the journal Lancet, in which they fed rats diets with identical nutrients, except for the type of starch. By the end of the study, rats in both groups weighed roughly the same, but those eating a high-glycemic diet had 71 percent more fat than the low-glycemic-index group.
- Inflammation. A diet high in grains stokes inflammation. When blood sugar spikes, glucose builds up in the blood significantly. When glucose drifts in the blood, it attaches itself to nearby proteins resulting in a chemical reaction called glycation, a pro-inflammatory process that plays a role in a host of inflammatory diseases.
- GI Disorders. Studies show that the lectins in grains inflame the lining of the gut and create fissures between cells. Also, when whole-kernel grains are refined, 80 percent of the fiber is lost, and gut health suffers. Additionally, fiber helps sweep the gut of debris and supports the body’s critically important elimination and detoxification processes, which also play a role in keeping high cholesterol and inflammation at bay.
- Acid-Alkaline Imbalance. The body has an elaborate system of checks and balances to keep its pH level at a steady 7.4. A diet high in acidic foods, such as grains, forces the body to pull calcium from the bones to keep things on an even keel. When researchers looked at how the diets of more than 500 women affected their bone density, they found that a diet high in refined grains, among other nutrient-poor foods, was linked to bone loss. A highly acidic diet also chips away at our cellular vitality and immunity in ways that can make us vulnerable to chronic disease. Grains are the only plant foods that generate acidic byproducts. Wheat, in particular, is among the most potent sources of sulfuric acid, a powerful substance that quickly overcomes the neutralizing effects of alkaline bases.
The Bottom Line….
Grains are not essential, and there is no nutrient in there that you can’t get from other foods.
Calories in food and calories as measured in physics are not the same. Nutritional calories exclude non-digestible components, excluding dietary fiber and artificial sweeteners; both of which could be burned in a bomb calorimeter to generate heat.
Many of these human non-digestible components, like cellulose, are the primary energy source for other specie
Human calories are dependent upon the body’s ability to catabolize them, usually involving enzymatic action; rather than a high-temperature oxidation reaction.
Reducing dietary saturated fats does not reduce cardiovascular events and death. Improvements in cardiovascular outcomes are independent of direct cholesterol lowering.
Dietary trials that provide abundant natural fats such as α-linoleic acid, polyphenols and Ω-3 fatty acids found in nuts, olive oil, oily fish, and vegetables exert a positive health effect, likely by reducing inflammation, atherosclerosis, and thrombosis.
A meta-analysis including almost 10,000 patients confirmed that high intake of Ω-6 oils (from vegetable oils/margarines) increases the risk of death and heart disease compared to saturated fat plus trans-fat. Human research data suggest that we should remove these vegetable oils from our food supply for optimal health.
Total and LDL cholesterol are a poor marker of cardiovascular health. The cholesterol profile of elevated triglycerides and low HDL is a more predictive marker of cardiac risk and a reliable marker of insulin resistance. In fact, the QRISK calculator, used to estimate the 10-year risk of CVD does NOT use LDL cholesterol but uses a total cholesterol/HDL ratio instead.
Preventing insulin resistance in young men would prevent 42% of myocardial infarctions, a larger reduction than correcting hypertension (36%), low high-density lipoprotein cholesterol (31%), body mass index (21%), or low-density lipoprotein cholesterol (16%).
Treating the root cause of the disease, instead of the symptom is the key. Eliminate all refined carbohydrates to reverse obesity, prediabetes, and type 2 diabetes.