Measles is the world’s most infectious disease. It has a basic reproductive number (R₀) of 12-18. That means that each infected person infects 12-18 other non immune people. As a result, 90% of susceptible people will get measles from exposure to 1 person with measles. The measles virus can linger in the air for 2 hours after a person with measles has left a room. Any susceptible person who enters that room during the 2 hour time period can be infected with measles. Here is a picture of a child with a typical measles rash.
Most US doctors have never seen a case of measles like this child. That, unfortunately is about to change.
For comparison of infectivity let’s look at the R₀ for other diseases we consider very contagious. R₀ for Ebola is 1.5-2.5, R₀ for COVID is 2.2-3.6 and R₀ for influenza is 1.2-1.4. As you can see none of these diseases comes even close to being as infectious as measles.
There are only two other diseases that are closer to being as contagious as measles. The R₀ for pertussis (whooping cough) is 5-17 (see my recent post on pertussis). The R₀ for varicella (chicken pox) is 10-12.
History of Measles in the US Prior to Measles Vaccine
Prior to the introduction of the measles vaccine in 1963, virtually all children in the US had measles by age 15. Having measles (and surviving it) provides lifetime immunity to measles, so adults born before 1954 have had measles and are already immune. People born before 1954 do not need to be vaccinated for measles.
Symptoms of Measles
Here is a description of measles symptoms from the Mayo Clinic
“Measles symptoms show up around 7 to 14 days after contact with the virus.
The first symptoms usually are:
Fever, which may be as high as 105 degrees Fahrenheit (40.6 degrees Celsius).
Dry cough.
Runny nose.
Red, watering eyes, called conjunctivitis.
About 2 to 3 days after the first symptoms, you also may see tiny white spots inside the mouth, called Koplik spots.
About 3 to 5 days after symptoms first start, or about 14 days after you come into contact with the virus, it’s common to see a rash. The rash is made up of large, flat spots and small raised bumps. The rash starts on the face or neck and spreads down the body from the chest to the arms and legs. A person with measles can spread the virus four days before the rash appears and four days after.”
Measles is obviously not a pleasant disease to have. Fever of 104-105 is pretty scary. All children with measles are miserable, but most children without complications recover from measles in about 10 days.
1 in 10 children with measles get bacterial ear infections that may need antibiotics
Hospitalization
About one in 5 children and adults with measles have to be hospitalized,
Pneumonia
One out of every 20 children with measles gets measles pneumonia. pneumonia is the most common cause of death from measles in children.
Encephalitis
One child out of every 1000 will develop encephalitis (inflammation of the brain). This condition can also cause death, but children who survive may have deafness and/or intellectual disability.
Death
Three children out of every 1000 children with measles will die from their disease, either from respiratory or neurological complications.
Subacute Sclerosing Pan Encephalitis (SSPE)
This is a uniformly fatal brain disease that can occur 7-10 years after a measles infection. Fortunately it is rare, but children who get measles before age 2 are at higher risk of SSPE.
Herd Immunity to Measles
The recommended regimen for MMR (measles, mumps and rubella) vaccination that gives the most protection is to be vaccinated at age 1 year and a second dose at age 4-5. This regimen gives lifelong 97% protection against contracting measles. This means that children under 1 year of age are protected only by everyone around them being immune to measles. Measles is a live vaccine (a weakened strain of the measles virus). People who have weakened immune systems because of chemotherapy or other causes of immune deficiency cannot receive live virus vaccines. Their only protection from measles is herd immunity. Herd immunity means that enough people are vaccinated or immune that a susceptible person who cannot be vaccinated is protected by the “herd” of people who are vaccinated.
Measles is so contagious that 95% vaccination rate is necessary to prevent measles entirely. Outbreaks start to occur if vaccination rates fall below 95%. Large outbreaks occur at vaccination rates below 90%.
In 2025 MMR vaccination rates ranged from a low of 75% in Idaho to 98% in Connecticut. Only 10 states had MMR vaccination rates above 95%.
MMR Side Effects
There are occasional side effects to MMR vaccine but the vast majority of those are mild. They include pain and swelling at the injection site, fever, a mild rash about 10 days after vaccination and some joint stiffness. When they happen these side effects disappear completely in a day or two. There are some very rare more serious reactions including febrile seizures (8 in 10,000 vaccinations), bruising or bleeding from low blood platelets (1 in 20,000 vaccinations) and severe allergic reactions (1 in 1 million vaccinations. Febrile seizure is scary for parents but does not recur and has no long term effects on the child. The other rare side effects are manageable. There are no known deaths from side effects of MMR vaccine. It is also important to point out that all of these side effects are much more common with measles infections.
MMR Vaccination Resistance
Worry about side effects of MMR vaccine has led to parents refusing MMR for their children. The main reason for vaccination resistance is worry that MMR vaccine causes autism. Very large well designed research studies have shown definitively that there is no connection between MMR vaccine and autism. The misinformation about MMR vaccine and autism unfortunately persists. This vaccination resistance has decreased the vaccination rate below the 90% threshold for serious outbreaks of measles in large parts of the US.
As you can see from this graph, measles cases started to rise after 2019 and went through the roof in 2025. 2026 is on track to have even more cases than 2025.
Deaths from Measles
Worldwide in 2025 95,000 children died from measles almost entirely from lack of measles vaccination. Three of those deaths were in the US. Given the resurgence of measles outbreaks across the US, we will undoubtedly see more deaths from measles.
Bottom Line
Measles is the most contagious disease in the world. Most children recover, but complications occur in 20% (one in five) children with measles. Complications include ear infections, hospitalizations, pneumonia, encephalitis and death. Vaccination rates must be at least 95% for complete herd immunity. Once vaccination rates fall below 90% large outbreaks of measles occur Vaccination rates are below 90% for large parts of the country and large outbreaks continue to occur in those communities with low vaccination rates. Measles is back with a vengeance!
A recent article in the journal Pediatrics reported a surge in cases of pertussis, commonly known as whooping cough. Unfortunately the article is only available to subscribers to the journal. Here is a link to a description of that article in a medical news service called Medscape. Pertussis is a bad disease. See below.
History of pertussis
Pertussis is caused by a bacterium, Bordatella Pertussis. Prior to the advent of pertussis vaccines, pertussis was one of the leading US causes of death of children under 5 years of age. There were over 200,00 cases and 9000 childhood deaths in the US from pertussis every year (a rate of 4.5 deaths per thousand children). Pertussis was especially lethal in infants, and was probably the leading cause of death in this age group. Worldwide, pertussis prior to vaccines was just as bad as in the US or worse. Worldwide there were 24.1 million cases and 160,700 deaths in children under five every year.
Epidemiology of pertussis
In un-immunized people pertussis is extremely infectious, almost as much as measles. One infected person on average infects 12-18 other people. In adolescents and adults pertussis is unlikely to cause death or hospitalization, but it is an extremely unpleasant disease. Older children and adults have paroxysms of coughing, followed by a loud, wheezing inspiration (the whoop of whooping cough). These symptoms can last for weeks or months. The coughing is sometimes so severe that people break ribs or develop hernias. Treatment with antibiotics is used to prevent transmission. Antibiotics are also given to contacts to prevent them from getting infected. Antibiotics do not have any effect on the length or severity of the disease. Those who have symptomatic pertussis just have to wait for it to go away. Here is an audio file of a child with pertussis. You should listen to it realize what a severe disease pertussis is. Let me warn you that it is distressing to listen to.
Pertussis vaccines
Whole cell pertussis vaccines
Whole cell pertussis vaccine combined with vaccines for tetanus and diphtheria was widely introduced and given to infants and children in the 1940’s. This was a highly effective vaccine. It not only prevented disease, but also prevented colonization and therefore stopped transmission of pertussis. It reduced the cases of pertussis by 75%. Unfortunately, the whole cell vaccine had rare but concerning side effects.These iincluded persistent crying, febrile seizures and hypotonic-hypoeresponive episodes (HHE). Children with HHE had sudden onset of reduced muscle tone, decreased responsiveness to verbal or other stimuli, and change in skin color (pallor or cyanosis) that occurred shortly after vaccination. These adverse events, though temporary were obviously distressing to parents. There were also rare cases of encephalopathy (Inflammation of the brain) that caused permanent disability. These cases were so rare that it was impossible to know whether these permanent disabilities were caused by the vaccine, or were simply associated but not causal. Controversy over whether the vaccine had any role in these cases continues even today.
Acellular pertussis vaccine
Because of the rare but distressing side effects of whole cell pertussis vaccine, a new vaccine was developed that had components of the pertussis bacterium, but not whole cells. This was called the acellular vaccine. This acellular vaccine had far fewer and milder adverse reactions than the whole cell vaccine. The combination vaccine is abbreviated DTaP (diptheria-tetanus-acellular pertussis). This is the vaccine used for children today. Unfortunately the acellular pertussis vaccine is less effective than the previous whole cell vaccine. It does prevent children from getting ill with pertussis, but it does not prevent colonization of the nose and throat. Children who are colonized in this way are not sick, but they are infectious and can pass on the virus to other children and adults. This keeps the bordatella pertussis bacteria circulating in communities.
Waning Immunity
Neither the whole cell nor the acellular vaccine provides lifetime immunity, unlike the Measles-Mumps-Rubella vaccines, which do provide lifetime immunity. Even people who have pertussis do not get lifetime immunity. Immunity from vaccines and infection wane over time. It appears that the acellular pertussis vaccine gives good protection from getting sick from pertussis for about 4 years, and starts to wane after that. The result is that we still see pertussis even in fully immunized children and adults starting about 5 years after the last routine immunization, which occurs at between 4 and 6 years of age. A booster TDaP is also recommended at around 12 years of age. This means that the most vulnerable children, that is children 5 or under are protected from getting ill from pertussis. Infants below 2 months of age (too early for vaccination) are protected by the recommendation that all pregnant women get a booster TDaP vaccine in the third trimester of every pregnancy. Anyone who is going to have extended contact with an infant under 2 months should also get a booster TDaP.
Risk of resurgence of severe pertussis
Bordatella pertussis continues to circulate in communities because of colonization of immunized children. Resistance to vaccinating children with DTap can quickly cause a resurgence of pertussis in infants and young children. This would be disastrous and is already happening. In 2024, there were 35,435 documented cases of pertussis across the U.S., including 655 in Colorado. That was a huge jump over the 7063 cases in all of 2023. Large states, including New York and California, logged high numbers of pertussis infections in 2024. So did some less-populated states like Idaho, Washington and Oregon, each of which reported more than 1,000 cases of pertussis. There were 10 deaths from pertussis in 2024. Cases are on track to be even higher in 2025.
Research on new pertussis vaccines
The search is on for a new pertussis vaccine that prevents colonization but that also does not cause the distressing side effects that happened with the whole cell pertussis vaccine. The best candidate at the moment is a live vaccine that has been genetically modified to eliminate the toxins produced by the bacterium. If and when approved this vaccine will be administered nasally. In rhesus monkeys it prevented colonization with bordatella pertussis and had no significant side effects. It is currently in phase 3 trials in humans.
Bottom Line
Pertussis is a serious disease and is life threatening to infants and young children. The severity and duration of pertussis are not affected by antibiotics that are given to limit the spread of the disease. The only effective treatment of pertussis is prevention through immunization. Acellular pertussis vaccine is much safer but also less effective than the old whole cell vaccine. It allows bordatella pertussis to continue to circulate in communities. Resistance to immunization of children has led to a marked increase in serious pertussis infections in 2024 with 10 deaths reported. Pertussis cases are on track to be even higher in 2025. A promising new attenuated live pertussis vaccine is in phase 3 trials and may soon be approved assuming research funding is not withheld by the Trump administration.
Longevity is the newest health buzzword. There are an increasing number of so-called longevity experts. They say, just read my book and follow my instructions and you can live past 100 years. Some of these “experts” focus on health span. They say follow my instructions and you will stay healthy and die suddenly at an advanced age. As of 4/21/2024 there are 34 books on longevity listed on Amazon.
In this post I will do my best to distinguish the hype from the science with regard to living a long and healthy life.
Hype
Calorie restricted diets – Some people have extrapolated mouse and rat experiments that show that animals fed restricted calorie diets live a lot longer than animals fed a normal diet. There is not one shred of evidence that this works with humans, and is more likely to lead to diseases of malnourishment.
Nutrtional supplements – Recommendations range from vitamins, to protein powder, to collagen powder, to herbal preparations, to encapsulated fruits and vegetables. There is absolutely no evidence that any of these things or any other supplements including multivitamins work to extend your life. Anecdotal reports of feeling better on these supplements are almost certainly a placebo effect
Anti-aging medicines – reservetrol, metformin, rapamycin have all been shown to prolong life in some experimental animals. In humans Metformin and reservetrol decrease the ability to exercise and rapamycin suppresses the immune system. There is no evidence whatever that these compounds increase life or health span in humans.
Extensive lab tests – Other than lipid (cholesterol) tests, there is no evidence that otherwise healthy non-obese people benefit from any blood tests. More about screening tests later.
Imaging tests – One of the most popular longevity “experts” ,Dr. Peter Attia, recommends full body MRI scans for his patients. Imaging tests in people who have no symptoms are much more likely to lead to over diagnosis and unnecessary treatment than to find things that really need to be treated,
Very intense exercise regimens – The only thing very intense exercise regimens accomplish that moderate exercise regimens do not is that the intense regimens are more likely to cause injury.
Science
Genetics
Up until into the 80’s, lifestyle is the major contributor to healthy aging. There are some people, however who remain healthy well into their 90’s and a few to past 100. Genetics is the main contributor to these “super centenarians.” There is not a single or even a few aging genes. Super aging is caused by hundreds of genetic variants called SNP’s (single nucleotide polymorphisms). We cannot alter our genes (yet), so there are no lifestyle changes you can make in order to live to 100 if you don’t have the rare combination of all these genetic variants.
That is not to say that lifestyle is not important to healthy aging. In the US, the average person’s last birthday in good health is age 65! Lifestyle changes will almost certainly help you do better than that.
Exercise
Regular exercise decreases your risk of chronic disease and therefore increases your chance of living healthier longer. To accomplish the maximum health benefit the CDC recommends 150 minutes of moderate exercise per week. Brisk walking or cycling at a moderate pace on level ground would qualify. If you choose high intensity exercise like jogging or running or high intensity cycling, you only need to do 75 minutes a week according to the CDC. The CDC also recommends activity to strengthen your muscles two days a week. For a population of adults doing this exercise regimen the risk of death is decreased by 17%. This regimen decreases the risk of heart disease, diabetes, certain cancers and decreases the risk of hospitalization or death from infectious diseases like COVID, flu and pneumonia. This regimen also increases bone and muscle strength and thus decreases the risk of falls and fractures. This exercise regimen also helps maintain a healthy weight.
Any amount of walking or activity decreases risk somewhat. The CDC recommended regimen decreases risk the most.
Nutrition
Eat mostly unprocessed foods and avoid ultra-processed foods. The best way to identify ultra-processed foods is to look at the ingredients label. If there are more than four ingredients, and/or if there are some you don’t recognize, then put that food back on the shelf. It is best to keep nutrition advice simple. The most concise recommendation I know comes from author Michael Pollan. “Eat food (food is anything your grandmother would have recognized as food), not too much, mostly plants.” I can’t do much better than that. Most of the evidence about the beneficial effects of good nutrition come from studies of the Mediterranean style diet. The Mediterranean diet adheres to Michal Pollan’s advice. It has lots of fruits, vegetables, fish, olive oil and very little meat. Adherence to this type of diet showed a 46% increase in living healthfully until 70 or greater.
Social Connectedness
The CDC defines social connectedness as the degree to which people have and perceive a desired number, quality, and diversity of relationships that create a sense of belonging, and being cared for, valued, and supported. An analysis of multiple studies showed that high social connectedness as defined above decreases the risk of premature death by 50%! High social connectedness also decreases the risk of heart disease, stroke and dementia.
Social Determinants of Health
The main reason that the US average health span is 65 years is the tremendous inequity of resources in the US. People who live in substandard housing (or no housing at all) do not have the opportunity or resources to do all of the things above that tend to extend life. That is why life expectancy at birth is related to zip code more than any other factor. My feeling is that we should expend our resources working on improving health equity, which will increase both life and health span for everyone rather than focusing on helping wealthy people live to 100.
Screening Tests
There are a few screening tests recommended by the US Preventive Care Task Force for healthy people. These tests are meant to find disease, especially cancer early so it can be more successfully treated and thus prolong healthy life. The absolute risk reduction of death for these tests is small, most around 1%, but that ends up saving a lot of people when you apply it to the whole US population. The recommended screening tests are listed below.
Mammograms for women beginning at age 50. Recommended every two years. Absolute risk reduction about 1%.
Pap Smears beginning at age 21 every 3 years through age 29 and then every 5 years from age 30 to 65. The absolute death risk reduction is .0009%, which means your would need to do pap smears on 11140 women to prevent one death from cervical cancer.
Colorectal cancer screening. There are three different tests: colonoscopy, the most invasive (recommended every 10 years), Cologuard (a stool sent to a lab in a box recommended every 3 years) and fecal immunochemical test (done on a stool sample and either tested at home or sent to lab recommended every year). All three tests reduce deaths from colon cancer with an absolute risk reduction of around 0.6%. Only colonoscopy can prevent some cancers by removing precancerous polyps.
Vaccines
There is no question that vaccines save lives by preventing some serious life threatening diseases, or making them less severe. Vaccines are especially important for infants and children, who are most at risk from the infectious diseases prevented by vaccines. Childhood vaccines prevent diptheria, whooping cough, tetanus, measles, mumps, rubella, polio, rotavirus (which causes severe diarrhea and dehydration in infants), hemophilus influenza (which caused joint infections and meningitis), hepatitis b, RSV (which causes severe respiratory illness), pneumonia caused by strep (the most common kind of bacterial pnuemonia), COVID (also for adults), meningitis, chicken pox, and HPV (the virus that causes cervical cancer in women).
Adults can get any of these vaccines, but also a vaccine to prevent shingles.
Bottom Line
Living in good health to past 100 depends on genetics, not lifestyle. Many things recommended by so called longevity experts do nothing to prolong life and may increase risk. There are a number of lifestyle changes including exercise, good nutrition, social connectedness, certain screening tests and vaccines that increase you chances of remaining healthy well into your eighties. The main cause of early death in the US is poverty, homelessness and systemic racism. Addressing these inequities is a lot more important than helping wealthy people try to live to 100.
Anyone who watches television these days is inundated by ads for supplements promising to improve your memory and your mental processing speed. In this post I will write about the evidence, or lack thereof that any of these supplements do what they promise.
Prevagen
The active ingredient in Prevagen is apoaequorin. It is a calcium binding protein found in luminescent jellyfish. When combined with calcium it causes bioluminescence (like a lighting bug). The manufacturer claims that taking Prevagen helps with brain health and improves aging related memory loss. The ads include testimonials from older people who say that Prevagen improved their memory.
There has been one clinical trial comparing apaequorin with placebo for improved verbal learning. It showed no benefit overall, but a subgroup analysis of people who had normal cognitive tests at baseline showed a slight improvement. Subgroup analyses in clinical trials are notoriously inaccurate. The FDA has not approved apaequorin for memory loss or for anything else.
In fact, apaequorin is a fairly large protein molecule, which means it is very unlikely to be absorbed into the blood stream at all. Proteins are broken down by acid in the stomach to their component amino acids and small peptides.
The bottom line is that Prevagen might combine with some calcium in your intestine and make the inside of your intestine glow in the dark, but it never leaves the intestine and so cannot possibly help your memory or your verbal learning. Any memory improvement that people report is almost certainly a placebo effect. The people giving testimonials on the Prevagen ads are actors reading from a script.
Balance of Nature
Balance of Nature sells fruit and vegetable supplements in capsules. The ads, like Prevagen, use actors reading a script. Like Prevagen, these fake testimonials report improvement in memory and learning. Here is the ingredients label for Balance of Nature fruit capsules:
Supplement Facts Serving size: 3 capsules Servings per container: 30 Amount per serving Calories 10 Total Carbohydrate 2g %DV* <1% Maintain Blend 731 mg † Tomato (fruit), Papaya (fruit), Banana (fruit), Apple (fruit), Grape (fruit), Wild Blueberry (fruit), Strawberry (fruit), Aloe Vera (leaf) Protect Blend 719mg † Orange (fruit), Tart Cherry (fruit), Cranberry (fruit), Wild Blueberry (fruit), Grape (fruit), Apple (fruit), Grapefruit (fruit), Aloe Vera (leaf) Repair Blend 561mg Raspberry (fruit), Pineapple (fruit), Mango (fruit), Sweet Cherry (fruit), Lemon (fruit), Aloe Vera (leaf) * Percent Daily Values (DV are based on a 2,000 calorie diet. †Daily Value (DV) not established. Other ingredients: Vegetable Capsules (cellulose).
Here is the ingredients label for the vegetable capsules:
Supplement Facts Serving size: 3 capsules Servings per container: 30 Amount per serving Calories 5 Total Carbohydrate 1g %DV* <1% Maintain Blend 720mg Broccoli (whole head), Spinach (leaf), Soybean (seed), Green Cabbage (head), Wheatgrass (leaves), Kale (leaf), Cauliflower (whole head), Celery (stalk), White Onion (bulb), Zucchini (fruit) Protect Blend 713mg Garlic (clove), Red Cabbage (head), Red Onion (bulb), Soybean (seed), Carrot (root), Kale (leaf), Cayenne Pepper (fruit & seeds), Shiitake Mushroom (whole), Wheatgrass (leaves), Sweet Potato (tuber) Repair Blend 576mg Carrot (root), Kale (leaf), Green Onion (scape), Soybean (seed), Spinach (leaf), Cauliflower (whole head), Celery (stalk), Zucchini (fruit) * Percent Daily Values (DV) are based on a 2,000 calorie diet. †Daily Value (DV) not established. Other ingredients: Vegetable Capsules (cellulose). Contains: Soy.
There is no question that all of these fruits and vegetables are good for you, but only if you eat them! You could not possibly get enough fruits, vegetables and fiber to do you any good from capsules. There is absolutely no evidence that these supplement capsules have any effect on your memory or anything else except your pocketbook. A bottle of both kinds of supplements costs about $90.00. I would suggest you take that $90 and go to the grocery store and buy real fruits and vegetables!
Ginko Biloba
Ginko Biloba îs an extract from the leaves of the Ginko tree. It has been used in chinese herbal medicine for centuries. The extract contains numerous compounds and extracts sold over the counter are not standardized and may have different combinations of these various compounds. Claims for ginkgo biloba include improved blood circulation, effects on symptoms of old age, and improved memory.
Some older studies did show some effects, but newer well designed studies show that these effects are no greater than the people who take placebo. A meta analysis (a review of multiple studies) showed that ginkgo biloba extract had no effect in the prevention of dementia.
Does anything improve memory and/or prevent dementia?
The answer is yes, but it’s not a pill or a supplement. Here are some things that improve memory and decrease the risk of dementia (they are going to look familiar):
Staying mentally active (reading books, learning new skills, writing, etc)
Regular exercise (especially walking outside)
Eating unprocessed foods, especially fruits and vegetables
Maintaining an active social life (time spent with friends and family)
Getting 7-8 hours sleep per night
Bottom Line
Heavily advertised supplements work no better than placebo to improve brain health or memory in older adults or anyone else. Although ginkgo biloba has been used in chinese medicine for centuries, the evidence shows that it too works no better than placebo.
Lifestyle changes outlined above are the only things that have been shown to improve memory and decrease the risk of dementia.
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.
This is an update and modification of an old post titled Immunizations. It seems particularly relevant now given the politicization of the whole subject of immunization in the last few years.
Many parents are concerned about the number of immunizations that are recommended for their children and whether all these shots may have some serious long term side effects. Public health recommendations that ignore these concerns have created an adversarial situation that is not helpful for parents or for their children.
Two Months: Hepatitis B, Tetanus-Diphtheria-Pertussis, H-flu, Pneumonia, Polio, Rotavirus (Six shots). That’s a lot of needle sticks for a baby! Fortunately there are combined vaccines that reduce the number of shots. Using the combined vaccines reduces the number of shots at two months from six shots to three shots.
Four Months: Same as two months except no Hepatitis B (three shots using combined vaccines)
Six Months: Hepatitis B, Rotovirus, Tetanus-diptheira-Pertussis, H-flu, pneumonia, Polio, flu shot, COVID-19 (four shots using combined vaccines) Another COVID-19 vaccination is recommended 4 weeks after the first one.
One Year: Polio, flu shot, Measles-Mumps-Rubella, Chicken pox, Hepatitis A (Four shots using combined vaccines).
Four Years: Tetanus-Diphtheria-Pertussis, Polio, Measels-Mumps-Rubella, Chicken pox (three shots using combined vaccines).
Nine Years: HPV vaccine. Second dose in 6 months to 1 year. HPV vaccine prevents infection with the wart virus also called human papilloma virus. HPV is the main cause of cervical cancer in women. It is transmitted through sexual intercourse. Given at age 9, the immunity is lifelong so immunizing children (girls and boys) means that as adults, when they become sexually active, there will be much less transmission of HPV and much less cervical cancer in women.
That’s a lot of shots, even with the combined vaccines, not even counting the HPV vaccinations recommended at age nine.. So one question is: Is the benefit of all these shots worth the discomfort to the children (not to mention the parents)? Another question is: Are there risks (other than temporary discomfort) to giving all these immunizations? A third question is: Does delaying immunizations for babies reduce any risks?
Let’s take these questions one at a time.
Vaccines clearly save children’s lives, so the answer to the first question is an unqualified yes! Most parents have never seen a case of polio, or diphtheria, or tetanus (lock jaw). The reason is that vaccines prevent them. These were devastating diseases that killed or paralyzed many infants and children. They have not gone away. If the immunization rate falls, we will see them again. We already have in communities where the immunization rate has fallen below a critical level. In times past, many children died from pneumonia caused by a class of bacteria called pneumococcus. The pneumonia shot has virtually eliminated this disease.
I have my own story about the Hemophilus influenza vaccine (Hib). Until this vaccine came out, I saw at least one child a year with a serious infection from this bacterium. It caused meningitis, joint infections and pneumonia. The sickest child I ever cared for had H-flu meningitis. Since the vaccine came out, I have never seen another case.
Rotavirus is a common cause of severe diarrhea and dehydration in infants, and some die from this. The rotavirus vaccine prevents this disease
Some parents wonder why we give vaccines for measles, mumps, rubella (german measles) and chicken pox. Most adults over 60 had these infections in childhood and recovered just fine. Unfortunately, lots of people did not do just fine. Measles can cause infection of the brain and pneumonia, Many people actually died or were permanently disabled by measles. The same story holds for chicken pox. Rubella (german measles) is a mild, self-limited illness except if a pregnant mother catches it. In that case it causes severe birth defects in the baby.
Another question parents often have is why we give hepatitis B vaccine to all children. Hepatitis B is transmitted by sexual intercourse or by needle stick, but it can also be transmitted to a baby during birth. The recommendation used to be that we gave hepatitis B vaccine only to babies of high risk mothers. That did not work very well because it was impossible to reliably identify high risk mothers. If you know for sure that neither parent has a chance of having hepatitis B, then it is reasonable to delay this vaccine until the child is older. The only way to be sure is for both parents to test negative for hepatitis B antibodies. Since you don’t know and cannot control what sexual experience your child will have later in life, this vaccine should at least be given before puberty.
A final question that parents have is about the COVID-19 vaccine for children. Why do we need to give the vaccine when most children have only mild disease? There are two reasons to give the COVID vaccine to babies. One reason is that although most children have only mild disease, some children get very sick and have to be hospitalized. The other reason we immunize babies and children for COVID-19 is to protect vulnerable adults that they may be exposed to. Most hospitalizations for COVID-19 now are older people and people who have other risk factors such a suppressed immune system, diabetes, COPD and other chronic diseases.
Now lets talk about risks of vaccines. I’m not talking about mild reactions such as a little irritability, low grade fever, or mild swelling at the site of the shot. That type of reaction is fairly common and self limited. The real question most parents have is about long term serious risks to immunizations. Here are some questions frequently asked by parents.
1. Do immunizations increase the risk that my child will get autism? The answer is no. There is one study often quoted by anti-vaccine groups that reported an association between childhood immunizations and autism. It turns out that the author of the study faked a lot of his data. It has been thoroughly discredited and in fact the journal that published it retracted it. Several very large well designed studies that were designed to answer this question found absolutely no connection between childhood immunizations and autism.
2. Do all these immunizations overstimulate children’s immune systems and increase the risk of autoimmune diseases later in life? The answer again is no. In order for the immune system to work properly, it is stimulated by literally thousands of environmental substances called antigens during a child’s life. It makes antibodies against these antigens so that children develop immunities to viruses and bacteria in the environment. The vaccine antigens represent a tiny fraction of all the antigens in the environment, certainly not enough to cause overstimulation. Studies have shown no connection between immunizations and autoimmune diseases such as multiple sclerosis, lupus, or rheumatoid arthritis
3. What about the mercury preservative in vaccines. Does that cause any long term problems? The preservative thimersol, which does contain some mercury, has been removed from all vaccines since 1992. There was no evidence that this caused any problems, but it is nonetheless not an issue anymore.
4. Did some children have severe reactions to the pertussis (whooping cough) vaccine?
The old pertussis vaccine was called a whole cell vaccine. It contained the entire inactivated pertussis germ. There were very rare serious reactions with this vaccine, including high fever and sometimes seizures. Now the pertussis vaccine does not contain the whole germ. It is called an acellular vaccine. Since the acellular vaccine was added to the diphtheria and tetanus vaccines (now called the DTaP vaccine), serious reactions were eliminated.
5. Can COVID-19 vaccine cause decreased fertility or other long term chronic disease?
A tiny number of adolescents who received the COVID-19 vaccine developed some inflammation of the lining around the heart. None of these children were hospitalized and all recovered completely. This did not happen when 6 month old children got the vaccine. There is no evidence whatever that COVID-19 vaccines decrease fertility in women or men. That is one of those pieces of misinformation that grow on the internet like weeds. We have seen no ill effects from the COVID-19 vaccine in infants.
6. Is there any benefit to delaying vaccines until children get older? Once again the answer is an emphatic no. There is no evidence of any health benefit to delaying immunizations. All of the diseases we immunize children against are most dangerous in infancy. Pertussis (whooping cough) and diphtheria killed many infants before we had vaccines to prevent them. All the other diseases we immunize against have a much higher chance of causing death in infants. If you delay your child’s immunizations, you are depending on everyone else getting immunized to protect your child. Not only is that not fair, but in some communities the immunization rate for infants has gotten low enough that you don’t even have that protection.
Bottom Line: Immunizations for infants and children are safe and effective. They prevent diseases that used to kill or maim many infants and children. The only downside is the discomfort of multiple shots, which can be significantly ameliorated by using combined vaccines. Delaying vaccines until children are older is dangerous for the child and provides no health benefits.
First, let me be clear about the definition of cancer screening. Screening for cancer is done for people who feel well and have no symptoms that suggest they might have cancer.The goal is to detect cancer early, before you have symptoms, so that hopefully it is easier to treat and cure.
If you have symptoms of cancer, then tests such as mammograms or colonoscopy are for diagnosis of a disease, not screening. If you are a woman who has a breast lump or abnormal uterine bleeding, or a man with a lump in the testicle, or anyone who has rectal bleeding or difficulty swallowing food, or feeling full after just a little food, you need to see your doctor right away and be tested for cancer. Here is a link to a web page from UCSF that has a more comprehensive look at symptoms of cancer for which you should see your doctor: 17 Cancer Symptoms You Shouldn’t Ignore.
In this post I am going to write about the available screening tests for cancer. For many cancers there are no good screening tests. A good screening test has to meet several criteria. The first is that it detects a kind of cancer that responds better to treatment when detected early. There are other criteria for a good screening test as well. Here is a link to a web page from the American Medical Society Journal of Ethics that talks about all the criteria for a good screening test: What Makes a Screening Exam “Good”?
I will discuss how well each of them work and how well they fit the criteria for a good screening test. I will also write about the risks of getting cancer screening tests (there are some substantial risks).
Cervical Cancer Screening (and Prevention)
Screening for cervical cancer is the poster child for an effective screening test. It is inexpensive, has no significant risk and detects both cervical cancer and pre-cancerous changes. It develops slowly, so it is an ideal cancer for screening. Early detection leads to much more effective treatment even before cancer develops. Since the 1940’s, when the pap smear was invented, death from cervical cancer has decreased by over 70%.
We have learned a lot about cervical cancer since the 1940’s. We now know that cervical cancer is caused by certain strains of the wart virus, otherwise known as HPV (human papilloma virus). The recommendation used to be that women should have a pap smear every year starting after beginning sexual intercourse. We now know that women under 21 most often clear HPV on their own, and there is no reason to do pap smears before age 21. If the pap smear is normal and the HPV test is negative, then for women 30-65 years of age, it is not necessary to do another one for five years. Women over 65 who have had two previous normal pap smears can stop cervical cancer screening.
Not only can the pap smear and HPV test detect cervical cancer early, but they can detect pre-cancerous changes that can be treated before cervical cancer develops. Even better, there is now a vaccine that prevents HPV and therefore cervical cancer altogether. It is called Gardisil, and should be given to adolescent girls and boys before the age they start having sexual intercourse.
Like other screening tests, most women will not benefit from cervical cancer screening. We would have to do pap smear and HPV screening on 1,140 women for ten years to prevent one death from cervical cancer. That means that 1,140 out of every 1,141 women will not benefit from cervical cancer screening,
Breast Cancer Screening
Mammograms are the primary and most studied screening test for breast cancer. Breast cancer is not as ideal for screening as cervical cancer, because some breast cancers develop very rapidly and can spread aggressively between mammography screenings. That means that some women die from breast cancer even if they get regular mammograms. Mammograms also have a high false positive rate, which can lead to more invasive unnecessary tests such as breast biopsies. The false positive rate for any kind of mammogram, including the newer 3D mammograms is 50% over 10 years!
Mammograms do save lives, but a lot fewer than people think. Here is a table from the US Preventive Services Task Force website that shows the benefits and harms of mammograms every two years for every 1000 women screened.
There are a few things to notice about this table. First, almost all the benefit in lives saved by screening is in the 50-74 age group but more false positives, unnecessary biopsies and overdiagnosis occurs in the group that starts mammography at age 40. The other thing to notice is the number of overdiagnosed breast cancers (overdiagnosed means that these tumors would never result in illness or death from the cancer) are much larger than the number of lives saved in each age category.
What this table says is that 125 women need to be screened with mammography to save one life from breast cancer. That is a great number! On the other hand, for every 47 women screened by mammography one woman gets overdiagnosed with breast cancer that would never harm her. That is a terrible number!
Given all this information, what should women do? Here are the US Preventive Services Task Force recommendations as of 2016. These recommendations are currently being updated, but the new recommendations are not available yet. The USPSTF recommends mammograms every other year, rather than every year. Every other year mammograms cut the risk of false positives in half, but result in the same number of lives saved.
The USPSTF recommends biennial screening mammography for women aged 50 to 74 years.
B
Women aged 40 to 49 years
The decision to start screening mammography in women prior to age 50 years should be an individual one. Women who place a higher value on the potential benefit than the potential harms may choose to begin biennial screening between the ages of 40 and 49 years. . For women who are at average risk for breast cancer, most of the benefit of mammography results from biennial screening during ages 50 to 74 years. Of all of the age groups, women aged 60 to 69 years are most likely to avoid breast cancer death through mammography screening. While screening mammography in women aged 40 to 49 years may reduce the risk for breast cancer death, the number of deaths averted is smaller than that in older women and the number of false-positive results and unnecessary biopsies is larger. The balance of benefits and harms is likely to improve as women move from their early to late 40s. . In addition to false-positive results and unnecessary biopsies, all women undergoing regular screening mammography are at risk for the diagnosis and treatment of noninvasive and invasive breast cancer that would otherwise not have become a threat to their health, or even apparent, during their lifetime (known as “overdiagnosis”). Beginning mammography screening at a younger age and screening more frequently may increase the risk for overdiagnosis and subsequent overtreatment. . Women with a parent, sibling, or child with breast cancer are at higher risk for breast cancer and thus may benefit more than average-risk women from beginning screening in their 40s.
C
Other groups recommend more intensive screening, but screening younger women and screening every year results in less than half a percent more lives saved and markedly increases the harms of screening including false positives and overdiagnosis. My feeling is that the USPTF recommendations make the most sense for women.
Prostate Cancer Screening
Screening for prostate cancer with the PSA (prostate specific antigen) is the most controversial of the cancer screening tests. Overdiagnosis with the PSA test is a huge problem. Autopsy studies done on men who died of other causes find that by age 80 more than half the autopsies show prostate cancer. Many, perhaps most prostate cancers grow so slowly that they will never cause any symptoms. More men die with prostate cancer than from prostate cancer. Overdiagnosis leads to radical prostatectomy for tumors that would never cause symptoms or death. Surgery for overdiagnosed tumors results in permanent urinary incontinence for half of men and sexual dysfunction for most of them. On the other hand, prostate cancer kills one out of every 41 men in the US. A good screening test for aggressive prostate cancer would be a wonderful thing. Unfortunately at this point we do not have such a test.
The US Preventive Services Task Force reviews all the available studies of screening tests and makes recommendations based on that evidence. Here is that review for the PSA test if 1000 men are screened with the PSA test annually for13 years,
Number of Men Affected
Men invited to screening
1000
Men who received at least 1 positive PSA test result
240
Men who have undergone 1 or more transrectal prostate biopsies
Men who initially received active treatment with radical prostatectomy or radiation therapy
65
Men who initially received active surveillance
30
Men who initially received active surveillance who went on to receive active treatment with radical prostatectomy or radiation therapy
15
Men with sexual dysfunction who received initial or deferred treatment
50
Men with urinary incontinence who received initial or deferred treatment
15
Men who avoided metastatic prostate cancer
3
Men who died of causes other than prostate cancer
200
Men who died of prostate cancer despite screening, diagnosis, and treatment
5
Men who avoided dying of prostate cancer
1.3
What this table shows is that of 1000 men screened for 13 years, there will be 100 men diagnosed with prostate cancer, but only 1 life saved as a result of screening and 2 other men who avoid metastatic prostate cancer. The cost of that life saved will be 97 men overdiagnosed with prostate cancer and 220 men that have a prostate biopsy. This is not a pleasant procedure and can sometimes result in complications such as infection, as indicated by the 2 men out of the 220 men that were biopsied that were hospitalized because of the biopsy. Five men out of the 1000 died from prostate cancer anyway despite screening, diagnosis and treatment,
African American men and men with a strong family history of aggressive prostate cancer are at substantially higher risk for aggressive prostate cancer. It is worth considering screening for this group. Men at average risk are more at risk for harm than help from prostate cancer screening, at least with the tests we have available now. The USPTF recommendation is that prostate cancer screening is an individual decision and should be discussed with your doctor.
Colorectal Cancer Screening
Colorectal cancer if caught early is almost 100% curable, but if it is not discovered until it invades the intestinal wall, the cure rate gets progressively worse.
Unlike breast cancer and prostate cancer, which have only one kind of screening test, there are a number of different screening tests for colon cancer. They each have advantages and disadvantages.
FOBT (Fecal Occult Blood Test)
This is the oldest test and also the one that has been studied the most. It is also the least expensive ($5-$10). People who do this test every year, and who have a colonoscopy if they have a positive test have reduced deaths from colorectal cancer by about 27%. That means that out of 1000 people who screen annually with FOBT, there will be 270 fewer deaths from colorectal cancer than people who do not do screening.
The biggest problem with this test is that it has a fairly low sensitivity of 50%, which means it will miss half of early colorectal cancers. It also has a fairly low specificity of 78%, which means that about 1/4 of the tests will be false positives.
FIT (Fecal Immunochemical Test)
This newer test is only positive for blood coming from the colon. That makes both the sensitivity and the specificity higher than FOBT. It is also fairly inexpensive (the home test costs about $25)
The sensitivity of the FIT test is about 75%, which means it will miss about 25% of early colorectal cancers. The specificity of the FIT test is about 90%, which means that the false positive rate is only 10%. Because the FIT test is relatively new, there are no randomized controlled trials of lives saved by FIT tests vs no screening. Estimates based on computer models suggest that annual FIT testing with colonoscopy for positive tests would reduce deaths from colorectal cancer by 74%! That means that of 1000 people who screen with the FIT test and get colonoscopy for positive tests, deaths from colorectal cancer will be reduced from 1782 deaths to 457 deaths.
There are several different kinds of FIT tests. Some require sending a stool sample to a lab, but the home test is just as good and is less expensive. The one that seems to work the best is from Pinnacle Biolabs. Here is a link to their website where you can order a test: Second Generation FIT® 1 Pack.
Cologuard
Cologuard is the only commercially available DNA test. It measures the specific DNA shed by cancer cells. It is actually a combination test and includes a FIT test as well. This increases the sensitivity, but decreases the specificity, which means that the Cologuard test has a higher false positive rate than the FIT test alone. It is also very expensive, about $600 per test. A stool sample has to be collected and sent to the lab. Computer modeling suggests that deaths from colon cancer for 1000 people would be reduced from 1782 deaths to 1143 deaths. Not nearly as good as the FIT test alone.
Colonoscopy
Although some groups consider colonoscopy to be a screening test, many organizations feel that colonoscopy should be used only when another screening test is positive. People who are at high risk of colon cancer should probably have colonoscopy as a screening test. Colonoscopy done every ten years, with follow-up exams every 3 to 5 years when polyps were found, would reduce deaths from 1782 deaths to 624 deaths.
Colonoscopy is the most sensitive and specific test, but also carries much more risk as a screening test. Serious complications (bleeding or perforation) occur in 44 people out of every 10,000. 3 people out of 100,000 die from colonoscopy. The average number of colonoscopies to result in one serious complication is 225. It is also very expensive (average cost $1,700). It may seem counterintuitive that FIT testing saves more lives, but that is because it is easy to do FIT testing every year and screening colonoscopies are done only every 10 years. One advantage of colonoscopy is that it reduces the chance of getting colon cancer by identifying and removing pre-cancerous polyps.
Lung Cancer Screening
For a long time we had no good screening test for lung cancer. Annual chest x-rays were shown to be worthless for lung cancer screening. Now there is a screening test for lung cancer. It is a low radiation dose CT scan. It should be done every year, but only for people aged 50 to 80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years.
False positives are a huge problem with lung cancer screening. Of people who get a positive result, 97% of those will be a false positive, meaning no cancer will be found on further testing. Further testing may include a needle biopsy of the lung, which can result in a collapsed lung.
The number needed to screen to prevent 1 lung cancer death is about 300. The number needed to harm (false positives or over diagnosis is 19. Although lung cancer screening with low dose CT does save lives, it comes at a substantial cost of false positives and overdiagnosis.
Common Cancers with No Good Screening Test
There are no good screening tests for ovarian cancer, uterine cancer, pancreatic cancer, esophageal cancer, leukemia, or Hodgkin’s disease (cancer of the lymph nodes. Many of these cancers are treatable once they are found, but they are found because of symptoms, not because of screening.
Galleri test
This is an update to this post, which I just published. Galleri is a new blood test that detects DNA shed by cancer cells. The company claims that it will detect 50 different types of cancer. Although this technology is promising, it is not yet ready for prime time. It is very good at detecting advanced cancer, but not very good at detecting stage 1 cancers when they are most treatable. There is also a high false positive rate of about 30%. Hopefully this technology will improve. If that happens, it will be a game changer with regard to cancer screening.
Bottom Line
If you are higher risk for any of the cancers for which we have screening tests, then getting screened is something you should do. If you are at average or low risk, screening tests are unlikely to help you and may harm you. Everyone should be alert for red flag symptoms that mean you might have cancer. The purpose of this post is not to discourage cancer screening, but to give you information that you should have when making a decision about whether and which cancer screening tests you choose.
This begins a series of posts on chronic diseases. Nearly half of Americans suffer from at least one chronic disease. Chronic diseases include diabetes mellitus, high blood pressure, cancer, stroke, heart disease, respiratory diseases, arthritis, obesity, and oral diseases. Chronic diseases are responsible for 7 out or every 10 deaths in the United States. Almost of these diseases can be prevented or managed successfully.
Type 2 Diabetes mellitus has reached epidemic proportions in the United States. One in every ten people in the United States has type 2 diabetes mellitus. It is the 7th leading cause of death in the U.S. In this post I will talk about the causes of type 2 diabetes mellitus, how it can be prevented, and how it can be treated by diet and exercise modification.
Terminology
The correct terminology for excesssive blood sugar is diabetes mellitus.The greek word from which the word diabetes comes means ”a large discharge of urine.” Mellitus comes from the greek word meaning “sweet.” There is another kind of diabetes (large discharge of urine) called diabetes insipidus, which is a completely different disease. Diabetes insipidus is caused by a deficiency of a hormone called vasopressin that is secreted at the base of the brain.
There are two types of diabetes mellitus and they both cause high blood glucose but they have completely different causes. Type 1 diabetes mellitus is an autoimmune disease that destroys the beta cells in the pancreas, which are the cells that produce insulin. It usually occurs in childhood, often following a viral infection. It is much less common than type 2. People with type 1 diabetes mellitus have high blood glucose because they produce no insulin at all and have to be treated with insulin. People with type 2 diabetes mellitus make plenty of insulin, at least in the beginning of the disease. Their bodies are resistant to insulin, and even though their insulin levels are high, the insulin can’t carry glucose into the body’s cells like it is supposed to and the blood glucose rises. In the rest or this post I’m going to talk exclusively about type 2 diabetes mellitus.
Causes of type 2 diabetes mellitus
Type 2 diabetes mellitus is caused by a complex interaction between genetics and environment.
Heredity
Type 2 diabetes mellitus tends to run in families. The lifetime risk of developing type 2 diabetes mellitus is 40% for individuals who have one parent with type 2 diabetes (I will leave off the mellitus from here on out for the sake of brevity) and 70% if both parents are affected. We know some of the genes that are associated with risk of developing type 2 diabetes but they only account for about 20% of the heredity, so there are a lot more genes to find. Genetic risk is not destiny, though. Environment plays a huge role in the development of type 2 diabetes.
Causes of Insulin Resistance
Insulin resistance is the hallmark of type 2 diabetes. Insulin resistance starts well before the onset of diabetes. At first your pancreatic beta cells make enough extra insulin to keep your blood sugar normal. Eventually, though, they can’t keep up and blood sugar starts to rise. A number of things can lead to insulin resistance, which I will outline below.
Abdominal body fat
Increased waist circumference (greater than 40 inches for men and 35 inches for women) is a marker for what is called visceral fat, which means fat around the internal organs. Visceral fat is one of the main causes of insulin resistance. Just being over fat in general is also a cause of insulin resistance.
Sedentary Lifestyle
Lack of regular exercise causes insulin resistance. I will talk more about exercise later on when I discuss preventing and treating type 2 diabetes.
Diet
A diet high in processed foods with starchy carbohydrates and sugar (or high fructose corn syrup) causes increased insulin release and can eventually lead to insulin resistance.
Microbiome
The microbiome refers to the 100 trillion bacteria that live in our intestinal tracts. The bacteria in the microbiome help digest our food, regulate our immune system, protect against other bacteria that cause disease, and produce vitamins including B vitamins B12, thiamine and riboflavin, and Vitamin K, which is needed for blood coagulation. It turns out that the microbiome may also promote or reduce insulin resistance depending on what kinds of bacteria live in our intestine. Research about this is just beginning, but here is what we know so far. People with type 2 diabetes have a lower diversity of bacterial species in their gut. They specifically lack bacterial species that produce something called butyric acid. Increased bacterial diversity in the microbiome and especially bacteria that produce butyrates are associated with lower insulin resistance. At this point we don’t know if changing the microbiome will help treat or prevent diabetes, but this is an exciting possibility.
Prediabetes
When genetic predisposition and environment interact, insulin resistance starts to develop. There is a condition called prediabetes. It develops up to ten years before people develop frank type 2 diabetes. There are two tests used to diagnose prediabetes (or actual type 2 diabetes). One is called fasting blood glucose. The blood glucose is tested after fasting overnight. Another test is called hemoglobin A1C. It turns out that glucose in the blood forms a molecular bond with the hemoglobin in red blood cells. This molecular bond lasts for the life of the red cell, which is about 90 days. The amount of hemoglobin that is bonded to glucose is proportional to the average blood glucose level over the 90 day life of the red cell. We can measure the amount of hemoglobin bonded to glucose and that gives us a pretty good measure of the average blood glucose over the last 3 months.
Prediabetes is defined as a fasting blood glucose of 100-125 and/or a hemoglobin A1C of 5.7%-6.4%. If either one of these values is higher, then that makes the diagnosis of type 2 diabetes.
The importance of finding prediabetes is that by making diet and lifestyle changes people can prevent the onset of type 2 diabetes. It is much easier to prevent type 2 diabetes than it is to treat it once you already have it.
How to prevent or reduce insulin resistance (whether you have prediabetes or have progressed to frank type 2 diabetes).
Increase your exercise. The CDC recommends 150 minutes a week of moderate exercise (brisk walking for 30 minutes, 5 days a week, for example) or 75 minutes per week of vigorous exercise (jogging or running for 25 minutes 3 days a week for example).
Avoid highly processed foods with added sugar, honey, maple syrup and especially high fructose corn syrup. Replace them with fresh fruit, fresh vegetables, fish and poultry.
Increase the soluble fiber in your diet. Soluble fiber promotes growth of diversity in your microbiome. Here is a link to an article from Healthline.com that identifies the top 20 foods with soluble fiber: Top 20 Foods High in Soluble Fiber
Eat fermented foods with live bacteria in them such as plain yogurt (sweeten with added fruit or berries, not sugar) sauerkraut, or kimchi. These add healthy bacteria to your microbiome. Here is another link to Healthline.com that lists a number of fermented foods that are good for you: 8 Fermented Foods and Drinks to Boost Digestion and Health.
Dietary Treatment of Type 2 Diabetes
If you already have type 2 diabetes you can do all of the things listed above to decrease insulin resistance, which means you may be able to get by on less or no medicines. If you are on any diabetic medicines other than metformin, you should let your doctor know of any changes you plan to make in your diet or exercise. He or she may want to reduce your medicines so you don’t get your blood sugar too low.
There are some additional dietary changes that may help your blood glucose be under better control and reduce or eliminate your diabetic medicines. These are things you definitely need to check with your doctor before you try them.
Ketogenic Diet
There is good evidence that a ketogenic diet is very good for people with type 2 diabetes.
What are ketones?
Normally your body uses glucose for energy for the brain and other body functions. Insulin carries the glucose into cells so they can use it for energy. If you don’t take in enough carbohydrates to produce glucose for energy, then your body starts to mobilize fat. Fat cannot be broken down to glucose, but it can be broken down to something called ketones. Your body and brain can switch over to using ketones for energy. Ketones require little or no insulin to get into cells.
What do you eat on a ketogenic diet?
A ketogenic diet is a very low carbohydrate high fat diet. That sounds unhealthy and it can be if you eat mostly saturated fats. A good ketogenic diet uses mostly healthy unsaturated fats. Here is a link to another Healthline.com article that discusses ketogenic diets for type 2 diabetes: How the Ketogenic Diet Works for Type 2 Diabetes. Do not start a ketogenic diet without checking with your doctor first!
Intermittent Fasting
Intermittent fasting means exactly that. Fasting means not taking in any calories for certain periods. There are all sorts of ways to do intermittent fasting. Most commonly, people fast for 24 hours every other day or they eat all their meals within a limited time period, between 7AM and 3PM for example. There is increasing evidence that intermittent fasting improves control of type 2 diabetes over and above the fat loss that results. Here is a link to a recent review article about the benefits of intermittent fasting for type 2 diabetes: Intermittent fasting: is there a role in the treatment of diabetes? A review of the literature and guide for primary care physicians.
It is important to drink plenty of water when doing intermittent fasting. If doing fasting for longer that 24 hours, one needs to drink liquids with electrolyes rather than plain water. People with type 2 diabetes should NOT start an intermittent fasting program without checking with their doctor.
Many parents are concerned about the number of immunizations that are recommended for their children and whether all these shots may have some serious long term side effects. Public health recommendations that ignore these concerns have created an adversarial situation that is not helpful for parents or for their children.
Two Months: Hepatitis B, Tetanus-Diphtheria-Pertussis, H-flu, Pneumonia, Polio, Rotavirus (Six shots) That’s a lot of needles sticks for a baby! Fortunately there are combined vaccines that reduce the number of shots. Using the combined vaccines reduces the number of shots at two months from six shots to three shots.
Four Months: Same as two months except no Hepatitis B (three shots using combined vaccines)
Six Months: Hepatitis B, Rotovirus, Tetanus-diptheira-Pertussis, H-flu, pneumonia, Polio, flu shot (three shots using combined vaccines)
One Year: Polio, flu shot, Measles-Mumps-Rubella, Chicken pox, Hepatitis A (Four shots using combined vaccines).
Four Years: Tetanus-Diphtheria-Pertussis, Polio, Measels-Mumps-Rubella, Chicken pox (three shots using combined vaccines).
That’s a lot of shots, even with the combined vaccines. So one question is, is the benefit of all these shots worth the discomfort to the children (not to mention the parents)? Another question is, are there risks (other than temporary discomfort) to giving all these immunizations? A third question is, does delaying immunizations for babies reduce any risks?
Let’s take these questions one at a time.
Vaccines clearly save children’s lives, so the answer to the first question is an unqualified yes! Most parents have never seen a case of polio, or diphtheria, or tetanus (lock jaw). The reason is that vaccines prevent them. These were devastating diseases that killed or paralyzed many infants and children. They have not gone away. If the immunization rate falls, we will see them again. We already have in communities where the immunization rate has fallen below a critical level. In times past, many children died from pneumonia caused by a class of bacteria called pneumococcus. The pneumonia shot has virtually eliminated this disease.
I have my own story about the Hemophilus influenza vaccine (Hib). Until this vaccine came out, I saw at least one child a year with a serious infection from this bacterium. It caused meningitis, joint infections and pneumonia. The sickest child I ever cared for had H-flu meningitis. Since the vaccine came out, I have never seen another case.
Rotavirus is a common cause of severe diarrhea and dehydration in infants, and some die from this. The rotavirus vaccine prevents this disease
Some parents wonder why we give vaccines for measles, mumps, rubella (german measles) and chicken pox. Most adults over 60 had these infections in childhood and recovered just fine. Unfortunately, lots of people did not do just fine. Measles can cause infection of the brain and pneumonia, Many people actually died or were permanently disabled by measles. The same story holds for chicken pox. Rubella (german measles) is a mild, self-limited illness except if a pregnant mother catches it. In that case it causes severe birth defects in the baby.
Another question parents often have is why we give hepatitis B vaccine to all children. Hepatitis B is transmitted by sexual intercourse or by needle stick, but it can also be transmitted to a baby during birth. The recommendation used to be that we gave hepatitis B vaccine only to babies of high risk mothers. That did not work very well because it was impossible to reliably identify high risk mothers. If you know for sure that neither parent has a chance of having hepatitis B, then it is reasonable to delay this vaccine until the child is older. Since you don’t know and cannot control what sexual experience your child will have later in life, this vaccine should at least be given before puberty.
Now lets talk about risks of vaccines. I’m not talking about mild reactions such as a little irritability, low grade fever, or mild swelling at the site of the shot. That type of reaction is fairly common and self limited. The real question most parents have is about long term serious risks to immunizations. Here are some questions frequently asked by parents.
1. Do immunizations increase the risk that my child will get autism? The answer is no. There is one study often quoted by anti-vaccine groups that reported an association between childhood immunizations and autism. It turns out that the author of the study faked a lot of his data. It has been thoroughly discredited and in fact the journal that published it retracted it. Several very large well designed studies that were designed to answer this question found absolutely no connection between childhood immunizations and autism.
2. Do all these immunizations overstimulate children’s immune systems and increase the risk of autoimmune diseases later in life? The answer again is no. In order for the immune system to work properly, it is stimulated by literally thousands of environmental substances called antigens during a child’s life. It makes antibodies against these antigens so that children develop immunities to viruses and bacteria in the environment. The vaccine antigens represent a tiny fraction of all the antigens in the environment, certainly not enough to cause overstimulation. Studies have shown no connection between immunizations and autoimmune diseases such as multiple sclerosis, lupus, or rheumatoid arthritis
3. What about the mercury preservative in vaccines. Does that cause any long term problems? The preservative thimersol, which does contain some mercury, has been removed from all vaccines since 1992. There was no evidence that this caused any problems, but it is nonetheless not an issue anymore.
4. Is there any benefit to delaying vaccines until children get older? Once again the answer is an emphatic no. There is no evidence of any health benefit to delaying immunizations. All of the diseases we immunize children against are most dangerous in infancy. Pertussis (whooping cough) and diphtheria killed many infants before we had vaccines to prevent them. All the other diseases we immunize against have a much higher chance of causing death in infants. If you delay your child’s immunizations, you are depending on everyone else getting immunized to protect your child. Not only is that not fair, but in some communities the immunization rate for infants has gotten low enough that you don’t even have that protection.
Bottom Line: Immunizations for infants and children are safe and effective. They prevent diseases that used to kill or maim many infants and children. The only downside is the discomfort of multiple shots, which can be significantly ameliorated by using combined vaccines. Delaying vaccines until children are older is dangerous for the child and provides no health benefits.
