The respiratory system, which includes the trachea, the bronchi and the lungs can be a source of chronic inflammation that not only affects the respiratory system itself, but can affect other organs as well. The inflammatory process in the respiratory system involves activation of the immune system just like chronic inflammation in any part of the body. It includes pro-inflammatory cytokines, macrophages and lymphocytes.
Causes of respiratory system inflammation
Nitrogen Oxides
Nitrogen oxides, particularly nitrogen dioxide (NO2) is a respiratory irritant that causes inflammation of the bronchi. Exposure to NO2 can cause or exacerbate asthma. In addition, several epidemiological studies have demonstrated associations between NO2 exposure and premature death, chronic lung disease, heart disease, stroke, decreased lung function growth in children, respiratory symptoms, emergency room visits for asthma, and intensified allergic responses. A comprehensive review of the health effects of NO2 exposure, both acute and chronic, can be found at this website: The Health Impacts of NO2 Pollution. The biggest outdoor source of NO2 is through reactions between nitric oxide (NO) and other air pollutants (mostly from automobile exhaust) that require the presence of sunlight. The biggest source of NO2 in home air is the use of unvented natural gas stoves.
Particles
In addition to gases like NO2, air pollution also contains particles. Large and medium size particles lodge in the nose and upper airways and are usually cleared by the airway protective system which includes mucus and cilia that move these particles up and out of the airways. Fine and ultra fine particles (those that are 2.5 microns and smaller) can get all the way down to the alveoli (the air exchange sacks) in the lungs. These tiny particles bypass the lung protective system and cause inflammation in the lungs. They can also sometimes get directly into the circulation and can cause damage in the heart and other organs. According to the EPA, a large body of scientific evidence shows that exposure to fine and especially ultra fine particles can cause heart attacks, heart failure, and strokes, which results in hospital admissions, emergency department visits, and, in some cases, premature death. The scientific evidence shows exposure to fine and ultra fine particles is also likely to cause respiratory effects, including asthma attacks, reduced lung development in children, and increased respiratory symptoms such as coughing, wheezing, and shortness of breath. Prolonged exposure can cause chronic lung disease such as COPD and pulmonary fibrosis. There is more limited scientific evidence for developmental and reproductive effects, lung cancer and other cancers.
Sources of fine and ultra fine particles
Outdoor sources of fine and ultra fine particles come primarily from automobile exhausts as well as some factories. They tend to be much higher in cities, particularly inner city neighborhoods.
Indoor sources are tobacco smoke, wood burning fireplaces, gas space heaters and natural gas stoves. The way food is cooked can also produce fine and ultra fine particles. Frying in hot oil or broiling generates lots of these particles even on electric ranges. Boiling or steaming generates many fewer particles. Air fryers also generate very few particles.
Reducing Indoor Air Pollution
Natural gas is 99% methane, so burning it in a stove in addition to generating dangerous levels of NO2 and fine and ultra fine particles, is also the most potent greenhouse gas. That means that not only are gas stoves bad for your health, they are also bad for the environment. If you have a gas stove, the best option is to replace it with at electric stove with an induction cooktop. Induction cooking is much more efficient than a traditional electric burner. It uses only 60% as much electricity and heats the pot directly rather than the burner itself. Heating with induction burners are actually faster than heating with gas burners. This is of course not practical for everyone. Replacing a stove is expensive and requires an electrician to install a 220 volt outlet if you don’t have one. It is also impossible for renters. If you can’t replace your gas stove and it has a hood that vents to the outside, turn it on high every time you cook. If the hood is not vented to the outside, then opening a window helps substantially decrease NO2 and particles. Whether you have either kind of stove, using a portable air fryer is much safer than frying in hot oil on the stove. Another much less expensive option is to purchase an induction hot plate. Good ones range from 60 to 200 dollars and can plug into a regular 110 volt outlet. Induction burners only work with pots that a magnet will stick to. That includes cast iron skillets and most stainless steel cookware. Inexpensive induction compatible cookware is available at a very reasonable cost from almost all big box stores such as Walmart and Target.
Reducing Outdoor Air Pollution
There is nothing an individual can do by themselves to reduce outdoor air pollution. Working to promote affordable electric vehicles is the only long term solution for automobile exhaust pollution in cities.
Bottom Line
Chronic inflammation of the respiratory system results from air pollution both outdoors (especially in inner cities) and indoors. Smoking tobacco is also a major cause of chronic inflammation of the respiratory system. Chronic inflammation of the respiratory system leads to many chronic lung diseases as well as heart disease and possible lung cancer. Indoor air pollution is caused primarily by unvented natural gas stoves as well as gas space heaters and wood burning fireplaces. The major causes of lung inflammation are nitrogen dioxide (NO2) and fine and ultra fine particles. Indoor pollution can be mitigated by ventilation using either a hood connected to outside or opening a window while cooking. Using electric induction burners are safer and heat even more quickly than gas. Portable electric air fryers are much safer than frying in oil on any kind of stove top. Purchasing an induction hot plate is a much less expensive way to do induction cooking. Reducing outdoor air pollution requires societal change.
All of the following discussion is taken from an excellent review paper: The Role of Inflammation in Cardiovascular Disease. It is not easy reading, so I’m going translate it into language that’s simpler for non-physicians to understand.
The cells that line the arteries in the body, including the arteries in the heart are called the vascular endothelium. In normal people, the endothelium has anti-inflammatory and antithrombotic (anti-clot forming) properties. It controls which molecules can cross it and which cannot. The endothelium also controls the smooth muscle contraction and relaxation which dilates or constricts the arteries. This takes place through the balance between the release of substances which dilate the arteries, such as nitric oxide (NO), and substances that constrict the arteries such as endothelin.
Effects of chronic inflammation on endothelium
Chronic inflammation from any cause reduces nitric oxide and endothelin, resulting in damage to the junctions between the endothelial cells. This allows larger molecules, like cholesterol to cross into the endothelial cells. When chronic inflammation is present, LDL (bad cholesterol) metabolism is shifted from large- and medium-size LDL particles towards small and dense LDL particles. These particles cause more atherosclerosis than larger ones because they are not cleared as well by the liver LDL receptors. They thus tend to persist in the circulation. These small dense LDL particles accumulate underneath the endothelium. These particles induce a local inflammatory response. White blood cells called macrophages engulf the LDL particles and release inflammatory cytokines. Many of these macrophages die forming a necrotic core. This stimulates the the formation of a fibrous collagen cap in the wall of the arteries over the LDL particles and dead macrophages.
From systemic inflammation to focal atherosclerosis
Even though inflammation is systemic, atheromatous plaques are focal. They tend to occur where arteries branch or on side branches because these areas are exposed to disturbed blood flow.
Stable vs unstable plaques
The plaques with the fibrous collagen caps when initially formed are stable. If chronic inflammation stops, then they remain stable and do not cause narrowing of the coronary arteries. If chronic inflammation persists then more macrophages continue to release inflammatory cytokines. These inflammatory molecules start to thin some of the fibrous caps making them unstable and prone to rupture.
What happens when a plaque ruptures?
When a plaque ruptures it exposes the interior of the plaque to the bloodstream. This activates the blood clotting system and a clot forms that can obstruct the artery. If it completely obstructs the artery it causes a classic heart attack, also called a STEMI (ST elevation myocardial infarction). The ST refers to a part of an electrocardiogram called the ST segment. In a classic heart attack there is elevation of the ST segments on the electrocardiogram. The elevation makes the electrocardiogram look like firemen’s hats. Here is an example of an electrocardiogram with marked elevation of the ST segments.
If the clot does not completely obstruct the artery the ST segments do not show elevation, but some damage to the heart muscle still happens. The symptoms of this kind of heart attack are similar to a classic heart attack with chest pain radiating to the arm or neck. This kind of heart attack is called an NSTEMI (Non-ST Elevation MI. It is usually detected by measuring enzymes that are released by the injured heart muscle.
Plaques that partially obstruct arteries
Even plaques that are stable and not in danger of rupture can get large enough to partially obstruct arteries in the heart. When these plaques obstruct more than 50% of the diameter of the artery they can cause symptoms. When a person exercises the heart muscle needs more blood and the obstruction limits the blood flow. In this case a person may get chest pain with exercise (angina) that goes away when they sit down and rest.
Strokes
Chronic inflammation causes exactly the same kind of changes in the carotid arteries and other arteries in the brain. Rupture of a plaque in these vessels can cause a stroke. Sometimes platelets adhere to a ruptured plaque in an artery that causes a transient obstruction of the artery that is then washed away by the blood stream. That results in temporary stroke symptoms that resolve in 5-10 minutes. This is called a TIA (Transient Ischemic Attack). A TIA can be a warning signal of risk of a bigger stroke. People who have TIA’s should be immediately evaluated for risk of a bigger stroke.
Treatment of vascular inflammation
Statins are a class of medicine that we used to think work primarily by lowering LDL cholesterol. It was later found that statins have a powerful anti-inflammatory effect. This may well be the major reason that statins reduce the risk of heart attack and stroke.
Bottom Line
Chronic inflammation results in changes in the endothelium of arteries in the heart and brain. These changes allow LDL cholesterol to accumulate in the endothelium causing fibrous plaques. Continued inflammation causes these plaques to become unstable and prone to rupture. Ruptured plaques cause blood clots to form which can lead to heart attacks and strokes. Statins have a powerful anti-inflammatory effect which may be the main reason they reduce the risk of heart attacks and strokes.
Inflammation is activation of the immune system in response to threat or injury to the body. Acute inflammation mobilizes the immune system to repair an injury or fight an infection. Once healing takes place the immune system goes back to baseline. Chronic inflammation, however, involves long term activation of the immune system caused by some ongoing stress to the body. More and more, researchers are beginning to show that chronic inflammation is the common pathway to many diseases. There are multiple causes of chronic inflammation. In this post I will write about the causes of chronic inflammation. I will also do a series of posts about the many diseases that chronic inflammation causes. These posts will be based on the structure of an excellent book: Inflamed – Deep Medicine and the Anatomy of Injustice. It is not easy to read because it is disturbing but I highly recommend it. I will also write about a test to measure chronic inflammation. I will write about things you can do to decrease chronic inflammation if you have it and how to prevent it if you don’t. There are many causes of chronic inflammation that have to do with the structure of our society. These are things an individual cannot control. These societal causes will take ongoing efforts by all of us to change some of the toxic structures of society.
The Process of Inflammation
The inflammatory process starts with damage or threat of damage to the body. That can be an infection, a wound, or perceived threat of such. The immune system mobilizes white blood cells called macrophages to the injured area or site of infection. The cells of the immune system also release a cascade of messenger molecules called cytokines that amplify inflammation. These include interleukin 1ß, interleukin- 6 and tumor necrosis factor -α. The liver also releases a protein called c-reactive protein. When the threat is neutralized the immune system helps the body start to heal by releasing anti-inflammatory cytokines including interleukin (IL)-1 receptor antagonist, IL-4, IL-10, IL-11, and IL-13.
In chronic inflammation the pro-inflammatory cytokines continue to predominate and the c-reactive protein continues to be elevated.
Causes of Chronic Inflammation
Causes an individual can do something about
Low levels of physical activity.
Having a BMI at or above 30 , especially when excess weight is deep within your belly (visceral fat). The best way to measure belly fat is to use a tape measure to measure your waist at the widest point. Increased belly fat is greater than 35 inches for women or greater than 40 inches for men
An imbalance of healthy and unhealthy bacteria in your intestine (dysbiosis). Dysbiosis can be caused by antibiotics and by eating foods low in soluble fiber.
Regularly eating foods that cause inflammation, especially highly processed foods, or foods high in sugar or salt
Inadequate sleep
Using tobacco products.
Regularly drinking too much alcohol
Periodontal disease (gum infection) and tooth decay
Perceived stress
Societal Causes
Experience of racism (structural or personal)
Poverty
Homelessness
Worry about debt
Work stress
Exposure to air pollution
Exposure to chemicals (pesticides and herbicides for farm workers, glyphosphate (RoundUp) for everyone, microplastics in our bloodstreams for everyone. Every day, we are surrounded by thousands of synthetic chemicals. They are in our food, clothes, tools, furniture, toys, cosmetics and medicines. We know the health effects of only a few of these).
All of the inflammatory cytokines can be measured but those are expensive tests. A simple inexpensive test that measures inflammation, both acute and chronic is high sensitivity CRP. It will also be high with an acute infection or injury, but will return to normal after the infection or injury have resolved. If it remains elevated when you are not sick or injured it is a sign of chronic inflammation. It may be worth asking your doctor to order this test if you have any of the individual or societal risk factors for chronic inflammation. A normal hs-CRP is less than 0.55 mg/dl in men and less than 1.0 mg/dl in women. If your hs-CRP is high in the absence of acute infection or injury, that can serve as motivation to make lifestyle changes to decrease your chronic inflammation and put you in a population that has less risk of developing any of the diseases associated with chronic inflammation.
Anti-inflammatory lifestyle
Exercise regularly. The CDC recommends 30 minutes of moderate exercise (walking briskly) for 30 minutes at least 5 days a week.
Eat mostly unprocessed or minimally processed foods and avoid sugary drinks or foods with added sugar or high fructose corn syrup. Also include foods with high soluble fiber such as beans, carrots, sweet potatoes, nuts, berries and most fruits (not fruit juice). Organic foods, while more expensive, have no residual pesticides or herbicides. If you eat meat buy grass fed beef, and pasture raised chicken and pork. Eat more plant-based foods than meat.
Avoid taking antibiotics as much as possible
Sleep. Average at least 8 hours a night
Floss your teeth daily, brush twice a day and see your dentist every 6 months
If you don’t smoke, don’t start and if you do smoke quit.
It is better not to drink alcohol at all, but if you do limit it to 1 drink a day or less.
Learn meditation or self hypnosis to manage stress. There are good books and videos, but an in person course is best if it is available.
Drink only filtered water and not bottled water in plastic bottles
Gas stoves cause significant indoor air pollution. If possible switch to an electric stove. Induction type burners actually heat more quickly than gas. If you have to use a gas stove, be sure to turn the ventilator fan on and open a window if possible.
Bottom Line
Chronic inflammation is the common pathway for many chronic diseases. There are many individual strategies that reduce or prevent chronic inflammation. Many of these strategies are not possible for people with socioeconomic problems. The stress black people experience from structural and individual racism, homelessness or inadequate housing, anxiety over debt, exposure to environmental synthetic chemicals, and exposure to air pollution are societal problems that we all have a responsibility to address.
My next post will deal with chronic inflammation and cardiovascular disease.
Humans have been drinking beverages containing alcohol for well over a thousand years. Mild to moderate acute alcohol intake has a euphoric effect probably caused by release of dopamine in the brain. At lower blood levels alcohol promotes social interaction, which is likely why it has such a long history of use in human society. The actual effect of alcohol on the brain is complex and not well understood. Brain function is a delicate balance of excitatory and inhibitory neurotransmitters. Alcohol alters this balance in a complex way that is difficult to measure and characterize.
Addiction to alcohol occurs in some people. About half of alcohol addiction is genetically determined. Other causes include use to alleviate mental disorders such as anxiety or depression or psychosocial stress. Physicians used to use the term alcoholism to refer to alcohol addiction, but now the correct term is alcohol use disorder. This can range from mild to severe and is defined by NIH as a medical condition characterized by an impaired ability to stop or control alcohol use despite adverse social, occupational, or health consequences. Severe alcohol use disorder has major health and social consequences for both individuals and society.
In this post I’m not going to write further about alcohol use disorder. That is a subject unto itself. Instead I’m going to focus this post on the health effects of alcohol use that does not meet the definition of alcohol use disorder, so called “social drinking.”
Physicians used to say that a safe level of alcohol use was 2 drinks a day for a male and 1 drink a day for a female. Now physician advice is that no level of alcohol use is safe. Alcohol use has been shown to increase the risk of many cancers as well as heart disease. The real question is how big is the risk for these conditions and at what level of alcohol intake.
Measuring alcohol use
The term “drink” is not very precise. I once had a patient who insisted she only had one drink a day. Her one drink consisted of a 12 ounce glass of vodka. The UK has developed a different measure of alcohol intake called units of alcohol. One unit of alcohol is the amount an average person can metabolize completely in 1 hour. That amount is 10 cc (1/3 of an ounce) or 8 grams of pure alcohol. Here is a list of the number of units in beer, wine and cocktails:
Four ounce glass of wine (red or white) – 1.5 units
Six ounce glass of wine (red or white) – 2.1 units
Eight ounce glass of wine (red or white) – 3 units
Low alcohol pint of beer – 2 units
High alcohol pint of beer – 3 units
Bottle of beer – 1.7 units
Cocktails – 2.5-3 units
If you drink alcohol, add up the number of units you drink per week. The greater the number of units per week, the higher the risk, which I will quantify below. Be aware that most of these risks are very small. There are quite a few people who don’t drink at all or drink only rarely. These people simply don’t have any desire to drink alcohol or don’t like the way it makes them feel. These essentially non-drinkers form the comparison group for the risk of drinking alcoholic beverages.
Risk of Alcohol Use Disorder
The vast majority of social drinkers do not develop alcohol use disorder, but people who have a family history of alcohol use disorder are at greater risk if they start social drinking. Social drinking is also not a good idea for people with severe anxiety or depression.
Risk of Cancer
Drinking alcohol increases the risk of certain cancers, particularly colorectal cancer, breast cancer, liver cancer, esophageal cancer, and throat cancer. The total absolute cancer risk for drinking greater than 14 units of alcohol per week from age 25 to 85 is 4% for men and 5.4% for women. That translates to an annual risk of .0667% for men and .09% for women. To put that risk in perspective, the annual risk of death from a car accident in the US is .013%. and the annual injury risk from a car accident is 1%.
Risk of Death
In a large study in the UK, risk of death from all causes was associated only with drinking more than 42 units of alcohol per week.
Accelerated Ageing
Recent studies have looked at two measures of biologic ageing. At the end of each chromosome are structures called telomeres. It is known that these telomeres shorten as a person ages. The other measure is called epigenetics. These are non-DNA changes that are heritable. Some of these epigenetic changes increase as a person ages. Recent studies show an association between alcohol intake and these biologic ageing changes. There seems to be a dose response relationship. The more alcohol you drink, particularly liquor as opposed to beer and wine, the more your telomeres shorten and epigenetic changes accumulate. This association was most marked in people with alcohol use disorder. There was little association for light to moderate social drinkers. Association does not mean causation, however the researchers controlled for other things that might account for these changes like smoking, diabetes, and others. It is possible and even likely that these ageing changes were caused by alcohol intake.
Risk of Accidents
Even mild to moderate drinking impairs reaction time so driving after drinking any amount of alcohol is not a good idea. Heavier drinking causes more impairment of motor function and increases risk of accidents such as falls. Driving after heavier drinking markedly increases the risk of auto accidents, which can injure or kill others as well as the one who is drinking. Anyone who drinks any amount of alcohol outside the home should have a designated driver who agrees not to drink, or call Uber, Lift, or a taxi to be driven home.
Sleep Disturbance
Drinking alcohol, particularly later in the evening can cause sleep disturbance with early awakening and difficult getting back to sleep. This can occur even with light to moderate drinking.
Bottom Line
Drinking alcohol at all does increase the risk of cancer and heart disease. The annual risk is dose related, but is still very small for light and moderate drinkers (14-21 units per week) The risk of illness and death and accelerated ageing is higher for heavier drinkers, but still relatively small. Drinking alcohol later in the evening often causes sleep disturbance. This can usually be avoided by timing drinking alcohol in the late afternoon or early evening. The risk of cancer and heart disease from drinking is low but not zero. People who choose to drink alcohol are accepting that risk. Driving is not a good idea for any level of alcohol intake. Light to moderate drinking is definitely less risky than heavier drinking, which includes association with accelerated ageing as well as increased risk of auto accidents. These risks are still fairly small. People who have alcohol use disorder should seek professional help and strive to be completely abstinent from alcohol.
It is expected that in 2024, 144 million people in the US will be using artificial sweeteners daily. The rationale for using non caloric or low caloric artificial sweeteners is of course to be able “to have your cake and eat it too.” That is, the sweet tooth can be satisfied without the known ill effects of sugar consumption. You can reduce your calories and therefore lose weight while still getting all the sweetness you crave. Is this true? Are artificial sweeteners safe? Do they help people lose weight? Are there ill effects from consuming artificial sweeteners over a long time? The answers to some of these questions are far from clear, but there is evidence to answer some of them.
There are six different sweetener compounds approved as food additives by the FDA. The FDA also approves the use of three plant and fruit based sweeteners as safe. To complicate things further, there are six FDA approved sugar alcohols (which have slightly less calories than sugar, but are metabolized differently). Below is a table listing all these sweeteners and their brand names. Scroll to the right to see the nutritive sweeteners in the table. Here is a link to the article containing the table
Used as an ingredient in food and beverage products
Stevia®, Truvia™, Sun Crystals®, PureVia™, Sweetleaf Sweetener™
Used as ingredient in food products.
XyloSweet
Used as ingredient in food products.
Zerose
The only thing all these compounds have in common is that they stimulate the human sweet taste receptor. Some are absorbed in the small intestine and some are not absorbed. They have (or may have) different effects on metabolism. Some of them are 2000 times as sweet as sugar and some (the sugar alcohols) are as sweet or half as sweet as sugar.
In this post I’m going to write about the pro and con evidence for each of these different classes of sweeteners. I’m also going to write about the effects of using honey, maple syrup and agave as sweeteners.
Human Taste
Humans have only five kinds of taste buds, mostly on the tongue, but some on the roof of the mouth and the throat. They are sweet, sour, bitter, salt and umami (spicy). All tastes are combinations of activity of these five kinds of receptors. Artificial sweeteners stimulate primarily the sweet taste buds. A few of them in larger quantities stimulate the bitter taste buds as well.
Do artificial sweeteners increase the risk of cancer?
The answer to this question is almost certainly no. There were some early studies of aspartame in rats that showed an increased incidence of bladder cancer. This turned out to be related to physiology specific to rats and not humans. There is no evidence at present to suggest that any artificial sweeteners increase the risk of cancer in humans. Obesity does increase the risk of cancer and many overweight people use artificial sweeteners. There is no evidence that the sweeteners themselves increase the risk of cancer.
Do artificial sweeteners help with weight loss?
The answer to this question is no. Almost all human and animal studies to date show no effect on weight loss or weight gain for any of the artificial sweeteners.
Do artificial sweeteners increase the risk of cardiovascular disease?
The answer to this question is probably yes. A large study in France showed that consumption of artificial sweeteners was associated with cardiovascular disease. The main ones consumed were aspartame, acesulfime potassium and sucralose. Apartame was associated with increased risk of stroke. Consumption of acesulfame potassium and sucralose was associated with an increased risk of coronary disease. Here is a link to that study in the British Medical Journal.
Do artificial sweeteners increase the risk of type 2 diabetes?
The answer to this question is complicated. The large study in France did show some increase in type 2 diabetes in the group that took the largest amount of artificial sweeteners. Some studies suggest that this effect may be due to the artificial sweeteners’ effect on the microbiome. Only sucralose, saccharine, and the sugar alcohols seem to affect the composition of the gut microbiome. It appears that people with certain kinds of composition of their microbiome are at risk of developing diabetes.
Other side effects of artificial sweeteners
People with irritable bowel syndrome may have increased symptoms from artificial sweeteners. People with inflammatory bowel disease (such as ulcerative colitis or crohn’s disease may have exacerbation of their symptoms from artificial sweeteners.
What about using honey, maple syrup, or agave as sweeteners?
Honey and maple syrup have some antioxidants that may be good for you, but they also have as much sugar as regular table sugar. Agave has mostly fructose as opposed to glucose, so it tends to make your blood sugar higher for longer. It also is only metabolized in the liver, and too much fructose can lead to fatty liver. Any of these in small amounts not too frequently is fine. The same is true for sugar.
Bottom Line
There are no health benefits to using any of the artificial sweeteners, including the ones derived from plants and fruits, and including the sugar alcohols. Evidence is accumulating that many of them may cause harm by increasing the risk of cardiovascular disease and adversely affecting the microbiome. You are much better off to use small amounts of sugar, honey, or maple syrup no more than a few times a week. You should avoid foods advertised as sugar free if any of the artificial sweeteners are listed on the label. Refer to the table at the beginning of this post to see what they are called.
Most people know these new effective weight loss drugs by their trade names: Ozempic, Wegovy and Mounjaro. Ozempic and Wegovy are different names for semaglutide. Mounjaro is the trade name for tirzepatide. All of these drugs are in the same class. They are called GL-P1 agonists. They mimic the action of a hormone called glucagon-like peptide. These drugs were developed to treat type 2 diabetes. They lower blood sugar by causing insulin release and also by delaying stomach emptying, which delivers less glucose to the bloodstream. The slowing of emptying from the stomach decreases appetite and causes an increased feeling of fullness. People on these drugs tend to reduce their calorie intake fairly markedly and that is how they work for weight loss.
Common Side Effects
The most common side effects of all these long acting medicines are nausea, vomiting, abdominal pain and diarrhea. These side effects usually disappear within a few weeks, and are less likely to happen if they are started at a low dose and increased gradually. Occasionally they are persistent. Some somewhat less common side effects include headache, fatigue, dizziness, constipation, heartburn, bloating, belching and flatulence (passing gas). People with diabetes can sometimes get low blood sugar. Again, most of these side effects usually go away within a week or two. Occasionally they can be persistent.
Rare Side Effects
These side effects are rare, but much more serious and can result in hospitalization. They include severe allergic reaction, acute pancreatitis, gall stones, acute kidney injury, suicidal thinking, and cancer of the thyroid.
Long Term Effects
The evidence so far is that stopping these medicines results in weight gain back to the original weight. That means that people are likely to have to stay on these medicines to maintain the weight loss. We know that the medicines are relatively safe when taken for two years, but we have no idea what long term side effects might be, or even if the medicines will continue to work past two years.
How well do they work?
The medicines are given by injection once a week and they work very well. These are the most effective medicines for weight loss that we have ever had, and there are some new ones in the pipeline that may even work better. As with any medicine, there are risks as I have documented above as well as benefits. You would not want to take one of these medicines unless the benefit exceeds the risk.
Who should take these medicines and who should not?
Obesity increases the risk of diabetes, heart disease and cancer, especially colorectal cancer. The best predictor of risk of disease from obesity is the waist circumference. Just take a tape measure and measure your waist at the level of the belly button. If you are female your risk of cancer starts to increase if your waist circumference is more than 31.5 inches. Your risk of cancer, especially colorectal cancer increases 5% for every inch above 31.5 inches. Above 35 inches the risk of diabetes, and cardiovascular disease starts to go up. For men the numbers are 37 inches for the risk of cancer going up and 40 inches for the risk of diabetes and cardiovascular disease.
The best treatment for obesity is prevention. That means eating unprocessed foods and regular exercise. If you are already overweight or especially if you are obese, it is very hard to lose weight and keep it off. Once you lose weight, your body thinks it is starving and all kinds of hormones and body changes kick in to try to get the weight back.
If your waist circumference is over 31.5 if your are female and 35 if you are male, then you are a candidate for one of these new weight loss medicines. For you the benefit likely outweighs the risk. If your waist circumference is less than those values, then the risk of taking these medicines is much higher than the potential benefit.
Cost
If your insurance does not cover medicines for weight loss the cost of these medicines may be prohibitive.
Wegovy costs $1,349.00 a month without insurance.
Ozempic costs $892.00 a month without insurance.
Muanjaro costs $1,300 a month without insurance.
Unfortunately many insurance plans do not cover weight loss medicines.
We have all been told for years that the main dietary risk factor for heart disease and stroke is how much saturated fat we eat. We have also been told that eating foods high in cholesterol also increases risk of heart disease and stroke. Evidence is accumulating that consumption of saturated fat increases risk of heart disease and stroke little if at all. Since your body makes cholesterol itself, eating cholesterol rich foods has almost no effect on serum cholesterol. Other aspects of diet have a much greater effect on increasing the risk of heart disease and stroke. In this post I will summarize the evidence and spend some time discussing things we eat and drink that do substantially increase the risk of heart disease, stroke and other chronic diseases.
The Seven Country Study
The most famous study that led to the saturated fat hypothesis was carried out by Ancel Keys. The study started in 1956 and was published in 1978. He looked at the dietary patterns of 7 different countries. The countries included Finland, Greece, US, Italy, Yugoslavia, Netherlands and Japan. He found that saturated fat intake was correlated with increased risk of heart attack and stroke. The country with the lowest saturated fat intake was Crete in Italy, which also had the lowest incidence of heart disease and stroke of the 7 countries. The diet of Crete is the basis for the famous Mediterranean Diet.
Diets of free living humans are notoriously difficult to measure. Keys did his best to accurately determine diet. He had a subset of his subjects in each country weigh their food for a number of days, which is considered the gold standard for dietary studies. The problem with any population study like this is that populations in different countries differ in lots of other ways besides diet. Also diets are complex, so some other factor or factors in diet could account for the low heart disease incidence in Crete. Another problem was that diet was measured in Crete during Lent, when most people did not eat meat. All Keys could really say was that saturated fat intake was associated with heart disease, but he could not say that saturated fat caused heart disease.
People who adhered to the Mediterranean Diet did reduce their population risk of heart disease, but there is a lot more to the Mediterranean Diet than reduced saturated fats. It also includes little added sugar, lots of vegetables and fruit and mostly unprocessed foods. It is not clear that reduction in saturated fat is responsible for the health benefits of the Mediterranean Diet.
The Framingham Study
The next big population study was the Framingham Study. A large group of people in Framingham Massachusetts was followed over many years with surveys about diet, activity, smoking and laboratory measurements of total cholesterol, LDL, HDL and triglyerides among other measurements. Heart attacks, strokes, death from either of these things and death from any cause were recorded in the study group. This was the first large study that implicated cigarette smoking as a cause of cardiovascular disease and cancer. It was also found that the higher the total cholesterol and especially the higher the LDL (low density lipoprotein) the higher the risk of cardiovascular disease. It was also one of the first studies that showed that the higher the blood pressure, the greater the risk of cardiovascular disease. This was a tremendously important and well done study.
The Diet-Heart Hypothesis
The diet-heart hypothesis is that saturated fat is the main dietary cause of cardiovascular disease. It has been very influential over 60 years and is still promoted by the American Heart Association and many cardiologists. Here is the train of thought. The 7 country study implicated saturated fat as associated with cardiovascular disease. It has been found through multiple studies that saturated fat intake raises LDL (so called bad cholesterol). The Framingham study showed that increased LDL was a major risk factor for cardiovascular disease. Since saturated fat raises LDL, therefore saturated fat must cause cardiovascular disease.
That makes perfect sense, so many randomized trials were carried out to nail down the diet-heart hypothesis. Unfortunately, as is often the case with beautiful theories, further randomized trials did not consistently show the expected increase in heart disease from eating saturated fat. The other part of the hypothesis was that eating polyunsaturated fats would decrease the population risk of heart disease. That was based on the observation that consuming polyunsaturated fats decreased LDL levels. Randomized trials have generally failed to consistently show that eating polyunsaturated fats reduces the risk of cardiovascular disease.
Reduced Risk of Cardiovascular Disease in US
Heart disease was epidemic in the US, peaking in the 60’s. Since then, the incidence of heart disease in the US and most other developed countries has decreased by 60%! Scientists debate the cause for this decline. Although saturated fat consumption decreased some, Americans still eat much more saturated fat than the 5% of fat recommended by the American Heart Association. So the fact that we eat somewhat less saturated fat does not explain the remarkable decline in heart disease over the last 60 years. What else changed?
Cigarette Smoking
In the 1940’s half of all Americans said they smoked cigarettes. Smoking began to decline in the US in the 60’s and today only 11.5% of Americans smoke tobacco! This has to be a major factor in the decline of cardiovascular disease (and lung cancer).
High Blood Pressure
High blood pressure is a major risk factor for heart disease. The number of people with high blood pressure successfully controlled on medicine has more than doubled since 1960. This is clearly another major factor in the decline of cardiovascular disease
Trans Fats
The rise of trans fat consumption was an unintended consequence of the heart-diet hypothesis. Because animal fat (mostly saturated fat) was postulated to cause heart disease, the food industry started figuring out how to use vegetable oil to replace lard and butter, which were high in saturated fats. They needed something that would be solid, not liquid at room temperature. They discovered that if they partially hydrogenated vegetable oil, then it would be solid at room temperature and could substitute for lard and butter. They marketed these products as healthier because they were only partially saturated fats, not saturated fats. The medical establishment bought this story and recommended margarine as a substitute for butter and Crisco (the most successfully marketed shortening substitute) as healthier alternatives. I have been unable to find statistics on trans fat consumption in the US, but it was very large.
It turns out that consumption of trans fats markedly increased the risk of cardiovascular disease. For every 2% increase in the consumption of trans fats, heart disease increased by 23%. This is a shocking number! The consumption of trans fats certainly contributed to the epidemic of heart disease in the 50’s and 60’s. The FDA essentially banned the addition of trans fats to food in June of 1978. The elimination of trans fats is almost certainly another major factor in the decline of heart disease.
Interesterification
Since trans fats have been banned, food companies have come up with a new way to make vegetable oil solid and spreadable. It is called interesterification. It is complicated, but the simplest explanation is that it involves changing the arrangement of fatty acids on a glycerol backbone. These are fully hydrogenated fats, so are not trans fats. We know very little about how these new industrial fats affect human health, but the information we do have suggests that these new products may be just as bad for you as trans fats. You would do best to avoid them until we know more. More about how to do this later in this post.
Do we need to limit red meat consumption?
The main risk of consumption of any food is eating too much of it. It is total calorie intake that makes us fat, and being fat increases the risk of cardiovascular disease, diabetes and some cancers. Eating red meat by itself is very unlikely to increase your risk of heart disease as long as your total calorie intake is equal to the calories you burn up. So there is very little health risk to you in eating red meat, but there is a big risk to the environment. Cattle raising worldwide contributes about 16% of greenhouse gas emissions. Here is a link to a balanced discussion of greenhouse gas emissions from cattle raising: Livestock Don’t Contribute 14.5% of Global Greenhouse Gas Emissions.
The other thing to think about when consuming any meat product, including chicken is that almost all the meat you buy in the grocery store comes from giant factory farms, where animals are treated very inhumanely. That in itself is bad enough, but raising all those animals together increases risk of spreading disease to the people who eat them. Antibiotics are used in many factory farms to keep animals from getting sick. This contributes to the evolution of bacteria that are resistant to most antibiotics.
If you are not willing to give up eating meat entirely, try to find locally raised beef, pork and poultry. Farmer’s Markets are a good place to find meat from locally raised animals. It may be a little more expensive, but likely a lot safer.
What about eating fish?
If you are at high risk of cardiovascular disease or have cardiovascular disease then eating oily fish (salmon, sardines, anchovies, herring, mackerel, tuna, swordfish) twice a week reduces your risk of a heart attack by 50%. If you are at average risk, these fish don’t have unusual health benefits but if you like them, it’s fine to eat them. Because most of these fish contain some mercury they should probably be avoided by pregnant women and children. If you get canned tuna, get Pacific Island Tuna at Walmart. It is sustainably caught. Here is a link to an article from the Nature Conservancy about it: The Nature Conservancy. By the way taking fish oil is not nearly as good for you as eating fish.
Highly Processed Foods
There are convincing data that consumption of lots of highly processed foods leads to health concerns ranging from increased risk of obesity, high blood pressure, breast and colorectal cancer, to dying prematurely from all causes.These foods all also contain additives whose health effects have never been adequately tested. How do you recognize them? Just look at the label where the ingredients are listed. If there are more than two things you don’t recognize, put it back on the shelf. Here is an example of an ingredients list from a loaf of bread!
This is not bread you would want to eat! If you mostly stay out of the central aisles of the grocery store you will avoid most highly processed foods. Just be sure to look at the ingredients label before you buy anything.
It is all well and good for me to make these recommendations, but highly processed foods and factory farmed meat are cheap. People who are poor cannot afford to buy anything else. This is only one of the things that have led to the major health inequities that are present in this richest country in the world.
Foods that decrease risk of cardiovascular disease
Fiber
Increased dietary fiber has been shown to decrease risk of cardiovascular disease. This may well have to do with promoting a healthy microbiome in the intestine. Sources of fiber that promote growth of healthy gut bacteria are ones that contain inulin. The highest sources of inulin are leeks, asparagus, onions, wheat, garlic, chicory, oats, soybeans, and Jerusalem artichoke. Sourdough bread (no added sugar, honey, or high fructose corn syrup) is also a good source of fiber. Whole grains, fruits, nuts and vegetables are also good sources of fiber.
Fresh Fruits
Fresh fruits are a good source of fiber and also contain many beneficial nutrients including vitamins and antioxidants. Data from multiple studies show that eating fresh fruit daily reduces risk of cardiovascular disease.
Nuts
Eating a handful of nuts per day reduces your risk of heart disease by 20%. Peanuts are technically of legume, not a nut, but legumes reduce the risk of cardiovascular disease as well. Unsalted nuts are better for you than salted.
Whole grains
Whole grains are also a good source of fiber and other beneficial nutrients. Eating whole grains most days is associated with decreased obesity, diabetes and heart disease. Examples of whole grains are
Barley.
Bulgur, also called cracked wheat.
Farro.
Millet.
Quinoa.
Black rice.
Brown rice.
Red rice.
Wild rice.
Oatmeal.
Popcorn.
Whole-wheat flour.
Whole-grain breakfast cereals.
Whole-wheat bread, pasta or crackers.
Make sure to read the ingredients label for cereals and crackers. Don’t buy anything that has more than two ingredients you don’t recognize.
Fresh Vegetables
Fresh vegetables are also a good source of fiber. Sorry folks, but potato chips and french fries do not count as fresh vegetables! Once again eating fresh vegetables daily significantly lowers your risk of cardiovascular disease.
Bottom Line
Eating red meat and saturated fats does very little to increase your risk of heart disease, but it also does not reduce your risk. Raising livestock on factory farms causes significant harm to the environment and puts people at risk of infectious disease. Eating meat from locally raised animals is safer.
Eating high fiber foods, whole grains, nuts, fruits and vegetable does substantially reduce your risk of cardiovascular disease as well as cancer.
Eating highly processed foods, and this includes the new industrial fats made by interesterfication increases your risk of cardiovascular disease and cancer. The biggest risk of these is probably because they encourage people to eat more calories than they need and have almost certainly led to the epidemic of obesity.
The most concise recommendation for a healthy diet comes from author Michael Poulin: “Eat food (food is anything your grandmother would have recognized as food), mostly plants, not too much.”
Medical care in the US is the most expensive in the world, but almost all our health outcomes are worse than other industrialized countries. We talk a lot about US populations that don’t have enough access to medical care, but this post is about people who get more medical care and procedures than they need. It turns out that too much medical care not only adds to costs, but is actually as bad for you as not getting enough medical care. I’m going to write about both diagnostic and surgical procedures that are unnecessary at best, and dangerous at worst.
Unnecessary Diagnostic Tests
Routine lab work at your annual preventive care visit
It is common for doctors to order “routine” lab work at preventive care visits. This often includes a complete blood count (CBC), a comprehensive metabolic panel (CMP), a lipid panel and a hemoglobin A1C (a long term blood sugar test).
Healthy people who are not overweight and have no symptoms don’t need any of these, except perhaps the lipid panel to screen for high cholesterol but not even that every year. If you are overweight and sedentary, then it makes sense to screen for diabetes or pre-diabetes with an annual hemoglobin A1C. If you have high blood pressure then it makes sense to do a basic metabolic panel, which includes a measure of kidney function once a year. Other lab work should be based on symptoms and risk factors.
One reason that doing unnecessary lab work is dangerous as well as costly is that the more tests you do on someone, the greater the statistical chance that at least one of them will be abnormal. That can lead to a cascade of further tests and even dangerous procedures.
Imaging for low back pain
There is no reason to do x-rays. CT scans or MRI scans for acute low back pain unless it lasts for more than 6 weeks. Imaging should be done sooner if “red flag” symptoms are present such as:
Fever or chills
Recent illness or surgery
Recent severe back injury
History of cancer
Unexplained weight loss
Night pain or pain at rest
Urinary or fecal Incontinence
Saddle anesthesia (loss of feeling in the buttocks and inner thighs)
Weak, numb, or painful leg muscles
Abnormalities on imaging, especially CT and MRI are often present in people who have no back pain. Imaging without red flags, could lead to unnecessary surgery or back injections.
CT or MRI scan for headache with no findings on neurologic physical exam
Headaches are common and the vast majority do not have a serious cause. Headaches without any other symptoms or history of head injury do not need any imaging. Headache in people who have a history of migraine headaches also do not need imaging. There are certain “red flag” symptoms that do require an immediate CT or MRI scan. These include:
Signs of systemic illness (e.g., fever, stiff neck, rash).
Worst headache ever.
Progression in frequency and severity of headaches.
New headache in patients older than 50 years.
Sudden onset of headache – “thunderclap headache.”
New-onset headache in an immunocompromised or cancer patient.
Headache after head trauma.
Headache worsening with Valsalva (straining like you do to have a bowel movement).
DEXA scan for osteoporosis in low risk women before age 65 and in low risk men before age 70
The risk of fractures due to osteoporosis is extremely low in women under 65 and men under 70 who have none of the high risk factors outlined below. DEXA scans in people in this low risk population are not only unnecessary but also result in unnecessary radiation exposure. Radiation exposure is cumulative and can increase the risk of cancer.
Risk factors for osteoporosis include: a family history of osteoporosis, previous fractures, dementia, poor nutrition, cigarette smoking, alcoholism, low weight and body mass index, estrogen deficiency, early menopause (i.e., before age 45) or prolonged lack of menstrual periods in premenopausal women, long-term low calorie intake, history of falls, and inadequate physical activity.
Ultrasound of carotid arteries (carotid dopplers) in people who have no symptoms
People who have no symptoms are unlikely to benefit from carotid stents or surgery even if they have partial obstruction of the carotid arteries. They are much more likely to be harmed by surgery including risk of stroke, heart attack, or even death.
Carotid dopplers are only indicated for people who have symptoms suggestive of a stroke or mini stroke (TIA)
Routine PSA screening for prostate cancer in men
Although a few men’s lives will be saved by routine PSA testing, many, many more will have surgery for slow growing prostate cancer that would never affect their health, resulting in urinary incontinence and sexual dysfunction for a good portion of those.
PSA screening for prostate cancer should always involve shared decision making with the patient. Some people who have a strong family history of prostate cancer or other risk factors may opt for screening. It should never be routine.
Prostate cancer screening should not be done at all in men over 70. The chance of finding anything other than low grade prostate cancer that does not need treatment in men over 70 is very low.
Annual EKG’s (or any other heart screening test) in low risk people without symptoms
Heart screening tests, including resting EKG and exercise stress testing in people in a low risk population have a much higher false positive rate than true positives. This can result in unnecessary invasive procedures including cardiac catheterization and unnecessary heart surgery.
People with multiple risk factors might benefit from screening tests. Here is a link to a heart disease risk calculator: CV Risk Calculator. You will need to know your LDL and HDL levels to use this calculator. If your 10 year risk is over 10%, you might benefit from one of the heart disease screening tests.
Pap smears under age 21 and over age 65
A pap smear is a screening test for cervical cancer, which is caused by chronic infection with the HPV (wart) virus. Women under 21 who are infected with HPV most often clear it without treatment. It therefore makes no sense to screen women under 21 for cervical cancer. Women over 65 whose last pap smear or HPV test was normal have almost zero risk of contracting HPV, so no longer need pap smears.
Annual pap smears are no longer needed for anyone. Pap smears are recommended every 3 years for women age 21-29 and every 5 years from age 30-65 as long as an HPV test is done also.
Unnecessary Procedures
Stents for stable angina
Stents in the coronary arteries can be life saving for heart attack or unstable angina (heart pain that is getting progressively worse). Many people, however have stable coronary disease. They get pain with a predictable amount of exercise that goes away when they rest. It stays the same and does not get worse with time. People with this kind of stable heart disease do just fine when treated with medicines and lifestyle changes. They do not need stents. In fact, stents do not decrease all cause mortality (death) 4 years later compared to treatment with medicines. Some studies suggest that up to half of coronary stent insertions are unnecessary. Stent insertion is an invasive procedure that can have complications including death. You definitely don’t want to have one if it isn’t likely to extend your life significantly.
Hysterectomy (removal of the uterus) for benign disease
Most “elective” hysterectomies are done because of fibroid (benign) tumors, excessive vaginal bleeding, or endometriosis. All of these conditions have alternative less invasive effective treatments. Fibroids that are causing symptoms can be removed without a hysterectomy. Persistent vaginal bleeding can be treated with hormones or with removal of the lining of the uterus without doing a hysterectomy. Endometriosis can usually be treated effectively with hormones. Hysterectomy should be done only for cancer or when alternative treatments for benign disease have been tried and have not been effective.
Knee arthroscopy for arthritis
Osteoarthritis of the knee is one of the most common chronic healthcare conditions. It involves gradual deterioration of the joint surfaces including tears of the menisci. Knee arthroscopy involves using a tiny camera to look inside the knee through a small incision. Another small incision is made to insert small surgical tools. When orthopedists recommend this procedure to patients, they often say that they are going to “clean out” the knee. This means removing fragments of torn cartilage and pieces of meniscus.
People get temporary relief if any from this procedure. It is considered unnecessary surgery. It exposes one to the risks of general anesthesia and possible infection from the procedure.
Vertebroplasty for osteoporotic compression fractures
Compression fractures of the spinal vertebrae are relatively common in women (or men) with osteoporosis. Many times these are not painful and are found incidentally on x-rays. Sometimes they are painful, especially when they first happen. Vertebroplasty involves injecting cement into the fracture site to stabilize it and reduce pain. Most of the time short term pain medicines and temporary spinal braces provide adequate pain relief. There have been no well conducted double blind studies of vertebroplasty, so it is not known how much of the pain relief from this procedure is simply a placebo effect. It may help in very selected patients, but should only be done for persistent pain when conservative measures have failed.
Spinal fusion for back pain
Chronic back pain is a common condition. It can result from arthritis of the spine or can still be present even with normal x-rays. Spinal fusion surgery connects two or more spinal vertebrae together with small screws. Bone chips from the hip bone are used at the site of surgery as a bone graft, which eventually fuses the vertebrae together.
Spinal surgery of any kind, but especially spinal fusion is never appropriate for people with chronic back pain who have normal back x-rays. Osteoarthritis of the lower back, which does show up on x-rays, is best treated conservatively with physical therapy, non-narcotic pain medicines and walking as much as tolerated.
Spinal fusion is only indicated when there is severe instability of the spine that is causing pressure on the spinal cord. This is not a common finding, so spinal fusion is only rarely indicated.
One problem with spinal fusion is that there is increased mobility of the spinal facet joints above the level of the fusion, which can cause recurrent pain. This can lead to another fusion, which is caused by the first one.
Bottom Line
Unnecessary diagnostic tests and lab work increase the probability of unnecessary surgical procedures. You should ask your doctor or nurse practitioner the reason for any diagnostic tests or lab work that they order. If the answer is “routine” then you should consider declining the test.
If any elective surgery (that means not emergency surgery) is recommended you should ask if there is a more conservative option. You may also always request a second opinion. For any of the low value procedures outlined above you should be very wary of having that procedure unless you have one of the red flag indicators.
All mammals, including humans have an innate response to perceived threat or stress. The more common name for it is the “flight or fight” response. Our remote ancestors faced many real threats. Let’s say for example one encountered a saber tooth tiger. As soon as he (or she) saw the tiger, several things happened. Epinephrine and norepinephrine were released, speeding up the heart rate in preparation for running away. A surge of cortisol was also released, which increased glucose in the bloodstream for fuel for muscles and the brain. Cortisol also increases mental alertness. Inflammatory molecules were released to promote wound healing should that be needed.
This kind of acute stress response is a good thing. People or animals with this kind of response were more likely to survive and reproduce. Once the acute threat was over, all the hormones and neurotransmitters quickly returned to their baseline levels.
In today’s world, threats from predators are not a problem for the vast majority of people. The threats we perceive are things like poor work conditions; experiencing discrimination, hate, or abuse; poverty; homelessness; divorce or other family discord; having little control over outcomes; feeling overwhelmed.
These are all things that produce the stress response, but unlike our remote ancestors, these threats are chronic. They are either lifelong or at least last a long time. Instead of returning to normal, the stress hormones and neurotransmitters stay elevated for long periods of time. A chronic stress response is definitely not a good thing!
Allostatic Load
The medical term for the acute stress response is called allostasis. Here is the definition of allostasis from Wikipedia: “Allostasis is the efficient regulation required to prepare the body to satisfy its needs before they arise by budgeting those needed resources such as oxygen, insulin etc., as opposed to homeostasis, in which the goal is a steady state.” Allostasis is an adaptive response to acute stress. Allostatic load on the other hand is the long-term result of failed allostasis, resulting in dysregulation (abnormal function) of multiple systems including the neuroendocrine, cardiovascular, immune, and metabolic systems.
Allostatic load is measured traditionally by 10 indicators of chronic stress. Primary indicators are the hormones and neurotransmitters released by stress. Secondary outcomes are measurements of the systemic effects of the primary indicators. All of these indicators are associated with the perception of stress. Below is a table showing the 10 indicators, how they are measured, and which body systems are affected. Here is a link to the full article from which this table comes: Allostatic Load: Importance, Markers, and Score Determination in Minority and Disparity Populations
Category
Marker
Functional purpose
Primary mediators
Dehydroepiandrosterone sulfate (DHEA), serum
Secreted by the adrenal glands. When high with stress it tends to lower cortisol and be protective in the stress response.
Cortisol, urinary
Integrated measure of 12-hour hypothalamic–pituitary–adrenal axis activity. Secreted by the adrenal glands. Has multiple effects in stress response.
Epinephrine, urinary
Integrated indices of 12-hour sympathetic nervous system activity. Sympathetic nervous system activation increases heart rate and blood pressure.
Norepinephrine, urinary
Secondary outcomes
Systolic blood pressure
Indices of cardiovascular activity and major risk factor for vascular disease
Index of long-term levels of metabolism and adipose (fat) tissue deposition. High value means fat around internal organs which increases inflammation and increases LDL (bad cholesterol) and triglycerides.
High-density lipoprotein cholesterol
Index of atherosclerotic risk protection. Low value increases risk of heart disease.
Total cholesterol
Index of long-term atherosclerotic risk
Hemoglobin A1C
Integrated measure of high blood sugar over 2–3 months
Each indicator that is a certain distance out of the normal range counts as one point. The score can range from zero to ten. The higher the score, the greater the risk of illness or death.
Other Indicators
Although the ten indicators were the ones described in the original papers about allostatic load, other indicators have been used as well.
Heart rate variability is the normal beat to beat variability in the heart rate. In a healthy heart there is slight variation in the timing of one heartbeat to the next. Chronic stress reduces or even eliminates this beat to beat variation.
High sensitivity C-reactive protein (CRP). This is a measure of systemic inflammation that can result from chronic stress.
How is the stress reaction triggered?
The stress reaction begins in the brain. Something in the environment is perceived in a part of the front of the brain called the prefrontal cortex. This is the executive decision maker in the brain. If the prefrontal cortex perceives something in the environment as a threat, then it sends messages to the limbic system (the part of the brain that is involved with emotions). It also sends messages to centers lower in the brain, especially the hypothalamus. The hypothalamus sends messages to the adrenal glands which secrete cortisone, norepinephrine and epinephrine. The hypothalamus secretes DHEA. Messages from the hypothalamus are also sent to the white blood cells which secrete inflammatory chemicals called cytokines. All of this prepares the body to deal with the perceived threat. Different people may perceive different things as a threat. It is the reaction to perceived threats that causes allostatic load. If another person experiences the same thing in the environment as not a threat, then there is no stress reaction.
Diseases associated with high allostatic load (high chronic stress)
A high allostatic load score is not disease in itself, but if chronic stress continues then disease in the cardiac, metabolic, neuroendocrine and immune system can occur. Here is a list of diseases associated with persistent high allostatic load.
Heart disease, primarily progressive blockage of the coronary arteries. This can lead to angina and/or heart attack. Congestive heart failure and arrhythmia like atrial fibrillation can also occur
Peripheral arterial disease. That is blockage in arteries in the legs and sometime fingers.
High blood pressure
Stroke
Autoimmune diseases like rheumatoid arthritis or lupus
Diabetes
Fibromyalgia
Chronic Fatigue Syndrome
Dementia or decreased cognitive function
Depression
PTSD
Cancer, particularly breast and ovarian cancer. The increase in cancer is probably related to decreased immune system function
Allostatic Load and Mortality
Many studies have shown that people with persistently hight allostatic load have about a 25% higher premature death rate than people with low allostatic load.
Disparities in Health Outcomes
The response to chronic stress (allostatic load) may explain some of the disparities we see in health outcomes. We know, for example that Adverse Childhood Events (ACE), which include things like abandonment and abuse, increase the risk of many chronic diseases in adulthood. Studies have shown that adults with a history of ACE have high allostatic load scores.
African Americans have higher incidence of many cancers, as well as poorer outcomes from those cancers. They also have worse outcomes from heart disease, high blood pressure and diabetes. While a good portion of these poorer outcomes are related to lack of access to health care, these disparities persist to some degree even in middle class and upper middle class African Americans. Almost all African Americans have experienced or still experience racism on a chronic basis. African Americans of all social classes have higher allostatic load scores than caucasians. Chronic stress and response to it may be the common denominator for these disparities as well as for health outcome disparities in other marginalized populations.
How to reduce allostatic load
There is typically a long time between the presence of indicators of allostatic load and illness and death caused by diseases associated with these indicators. That presents an opportunity to reduce allostatic load before the chronic stress response leads to illness and death. So how do we reduce allostatic load?
Some of the things that cause allostatic load can only be reduced by societal changes. Things like poverty, structural racism and homelessness cannot be decreased by individual effort. Even these causes, though, can respond to the mind body methods discussed below. On the other hand, if you don’t have enough to eat, have no home, or have a job that gives you no control of your life, it is not likely that you will have the energy or the will, or the financial means to do many of the mind body methods discussed below. We should not be distracted from working to decrease the inequities that are responsible for societal causes of chronic stress.
Mind-Body Medicine
Remember that an external threat is first received by the peripheral nervous system and transmitted to the pre-frontal cortex. In order to reduce allostatic load we can either reduce the threat perception in the prefrontal cortex (top down) or reduce the transmission of threat in the peripheral nerves (bottom up).
Top Down Treatments
Top down treatments start with intentional activity in the prefrontal cortex. The idea is to decrease activation of the limbic system and the hypothalamus. This can be accomplished by mindfulness meditation, hypnosis (including self hypnosis), mental imagery and progressive muscle relaxation. All of these techniques when done regularly have been found to decrease allostatic load indicators and to reduce the risk of stress related illnesses.
Bottom Up Treatments
Bottom up treatments decrease the threat transmission to the prefrontal cortex. They include yoga, Tai Chi, massage and biofeedback. These treatments have also been shown to decrease allostatic load and to reduce stress related illness.
Bottom up and top down are somewhat of an oversimplification. All of these treatments have some aspects of both top down and bottom up. Yoga, for example includes aspects of meditation. The same goes for Tai Chi. Biofeedback involves some attention from the prefrontal cortex. Massage also includes progressive muscle relaxation.
Bottom Line
The body’s reaction to a perceived threat includes a complex cascade of messages from the executive center in the prefrontal cortex to multiple body systems including the nervous system, the endocrine system, the cardiovascular system and the immune system. All of these things prepare the body to deal with the threat. As long as the threat is short term the stress response is very useful to the organism.
Perception of chronic stress leads to continuous secretion of all the stress hormones and inflammatory cytokines and this leads to dysfunction of multiple body systems and eventually to illness and death.
Mind body treatments, both top down and bottom up can reduce the allostatic load (chronic stress response) and reduce the risk of stress induced illness and death.
Many causes of chronic stress have to do with the structure of our society, such as poverty, homelessness and structural racism. Individual effort is not likely to ameliorate the effect of these causes of chronic stress. All of us should be working toward societal change to reduce chronic stress response in marginalized populations.
Cholesterol is one of two fats in the bloodstream called lipids. Your liver makes almost all the cholesterol in your blood. Eating high cholesterol low saturated fat foods (such as eggs and shellfish) does not increase your blood cholesterol. The other fat is triglyceride. Almost all triglyceride comes from what we eat or is made in the liver from foods that have a lot of sugar or starchy carbohydrates. Fat does not dissolve in the blood, so these fats are carried in tiny droplets within a protein shell. These proteins are called lipoproteins. Any of these lipoproteins can be elevated without the others, so although many people may say, ”I have high cholesterol,” it is important to know what kind of ”high cholesterol” they have. In this post I will talk about the different kinds of hyperlipidemia (the medical term for high cholesterol), what kind of damage they can do, and how they can be treated both with medicines and diet.
Types of lipoproteins
There are four major classes of lipoproteins: chylomicrons, very low density lipoproteins (VLDL), low density lipoproteins (LDL) and high density lipoproteins (HDL).
Chylomicrons
Chylomicrons are the largest particles. They carry fat that you eat from the intestine to be used as fuel for the body or stored in fat cells. They are made mostly of triglycerides (90%), which is in the center of the particle with several different kinds of lipoproteins on the outside.
VLDL (very low density lipoproteins)
This is the next smallest class of particles. They contain about 50% triglycerides, 25% cholesterol and the rest a type of fat called phospholipids. They are made in the liver and carry triglycerides and cholesterol to the cells.
LDL (low density lipoproteins)
LDL particles carry more cholesterol than the others. They also deliver cholesterol to the cells. High levels of LDL particles are associated with an increased risk of heart disease. More about this later.
HDL (high density lipoproteins)
HDL particles have the most protein and the least amount of fat contained within them. That makes them more dense, hence the name, high density lipoproteins. The function of HDL particles is to carry cholesterol and triglycerides back from the cells to the liver. This decreases LDL in the cell walls of the arteries and helps prevent heart disease. Low levels of HDL are associated with increased risk of heart disease and high levels with decreased risk of heart disease. Paradoxically, very high levels of HDL actually increase the risk of heart disease.
Cholesterol
Cholesterol is essential to your body. Cell walls are made up of mostly cholesterol. Cholesterol is used to make many essential hormones in the body including estrogen, progesterone, androgen, cortisol and many others. Cholesterol moves in and out of cells to do it’s job. If LDL (and therefore cholesterol) is too high, it can accumulate in the walls of arteries at spots where there is inflammation. More about inflammation later. The immune system sends special cells called macrophages to ”eat” the offending LDL particles, but that causes more inflammation and more accumulation of cholesterol. This cholesterol buildup is called a ”plaque” and these can cause narrowing of the artery and can also cause blood clots to form which can completely block the artery. The result is a heart attack or stroke.
Triglycerides
Triglyceride levels are affected by what we eat. We absorb triglycerides directly from eating saturated fats but the liver also converts any unneeded calories to triglycerides that are then stored in fat cells. Very high triglyceride levels can cause pancreatitis (inflammation of the pancreas). It is likely that high triglycerides also increase the risk of heart disease and stroke, possibly by being deposited in the arterial walls like cholesterol. We are not sure at this point the exact mechanism that connects high triglyceride with cardiovascular disease
Inflammation
Inflammation in the artery walls starts the whole process of cholesterol buildup and plaque formation. In fact, one of the main reasons that statin drugs like atorvastatin (Lipitor) work is that they reduce inflammation in the walls of the arteries as well as lowering LDL (and thus cholesterol). It may well be that inflammation of the artery walls can cause plaque formation to begin even in people with normal LDL levels. We can get some idea how much chronic inflammation is going on in our bodies by having a blood test called high sensitivity C-reactive protein (CRP).
So what causes inflammation of the artery walls and is there anything we can do about it?
Inflammation is increased by our old friends: highly processed foods, sugar, high fructose corn syrup and a diet high in starchy carbohydrates. There is pretty good evidence to suggest that eating large amounts of saturated fats (essentially animal fats) also produces inflammation. Increased belly fat secretes a substance that causes chronic inflammation (See my previous post Why is the United States so fat and what to do about it for instructions about how to measure your belly fat). Finally, inflammation of the gums from plaque on your teeth leads to inflammation in arteries. Of course smoking cigarettes also increases inflammation in your arteries.
You can reduce inflammation in your arteries by stopping smoking if you are a smoker, eating unprocessed foods, especially fresh vegetables, fruits and berries, nuts and fatty fish. Taking good care of your teeth also helps. That means flossing daily and seeing the dentist for cleaning once every 6 months. Regular exercise such as walking at least five times a week also reduces inflammation. If your abdominal circumference is above normal, then losing weight will reduce inflammation. All of these things also tend to reduce LDL and triglycerides too, so you get double duty from these life style behaviors.
When you need to take medicine for hyperlipidemia
A significant portion of high LDL and/or triglycerides is genetic. You can make all the lifestyle changes I talk about above and still have high lipids. If that is the case, then you need to talk to your doctor about starting cholesterol medicine. That will likely be one of the class of drugs called statins. There are quite a few of these and they vary in potency, side effects and drug interactions. Almost everyone will be able to tolerate one of the statins without any significant side effects. There are a few people that have adverse reactions to all of the statins. There are some new non-statin medicines that look promising for decreasing LDL in those few patients who can’t tolerate statins. Your doctor will help you find the right medicine for you to help lower your LDL and/or triglycerides.
Bottom Line
All fats in the blood are carried by special proteins called lipoproteins. Cholesterol is carried mainly by LDL. In the presence of inflammation in the arteries, high levels of LDL lead to plaque formation in the arteries that can eventually lead to heart attack or stroke. High levels of triglycerides also increase the risk of heart disease. Lifestyle changes can reduce both inflammation and number of LDL particles and triglycerides, thus reducing population risk of cardiovascular disease. Sometimes lifestyle changes are not enough and cholesterol lowering medicines are needed.
