Science Is Real

Science is real. Science is also slow, and sometimes science takes detours. A May 2018 column was about the rise and fall of vitamin E. Briefly, back in the 1990s, claimed benefits led with reducing risk of cardiovascular disease and some types of cancer, but piled on with claims for results for macular degeneration, pregnancy, dementia and other diseases. With no apparent concerns about safety, there was a race up to mega-dose amounts being widely sold as non-prescription dietary supplements. Then the bad news – results from large, placebo-controlled human trials – started to trickle in. As Thomas Huxley put it, “The great tragedy of science – the slaying of a beautiful hypothesis by an ugly fact.”

Yes, vitamin E was confirmed as an antioxidant, and the oxidation theory of diseases of aging is one of cumulative damage. Healthcare professionals who chose to consume a vitamin E dietary supplement had a 1/3 reduction for risk of cardiovascular disease. Sadly, subsequent years-long clinical trials concluded that there was at best a modest reduced risk of heart attack at low doses, increased risk at high doses, no benefit for risk of stroke, and no improvement in all-cause mortality. With hindsight, in the initial research, health professionals who had decided to consume vitamin E supplements may have made other lifestyle decisions that promoted good health. It is an example of correlation not necessarily reflecting causality. Research for other diseases also had mixed results: nothing for pregnancy, nor hair, nor for topical applications for burns or wound healing; mixed results for cancer. There was a trickle of evidence that amounts over 200 mg/day had negative consequences. Sales of dietary supplement vitamin E declined dramatically.

Niacin is both a vitamin and a prescription medication. As a vitamin, intake recommendations made by several countries are that for adults, intakes of 14–18 mg/day are sufficient to meet the needs of healthy people. When niacin is used as a medicine to treat elevated triglycerides and serum low-density lipoprotein cholesterol (LDL-C), daily doses range from 500 to 3,000 mg/day. The LDL-C lowering effect was discovered by accident; niacin was being investigated as a treatment for hypertension, and then in 1952 a group of Russian scientists reported cholesterol-lowering as a side effect. Prescription niacin became widely used as a hyperlipidemia treatment drug some 30 years before the approval of the first statin drug in 1987.

All that is well and good and still true, although the advent of statins, which were more effective that niacin and with fewer side effects, reduced niacin prescriptions by 90 percent. Where niacin veered into a science detour was a second purported health benefit. In addition to lowering LDL-C, niacin also raises high-density lipoprotein cholesterol (HDL-C), often referred to as “good” cholesterol. Population studies showed that people with higher HDL-C were at lower risk for cardiovascular disease. Lifestyle interventions that raised HDL-C, such as exercise or moderate consumption of alcohol, also correlated with lower risk. Collectively, this suggested that HDL-C was a valid biomarker. However (the beautiful hypothesis slain by the ugly fact), niacin in combination with a statin drug proved no better for clinical outcomes than the statin alone, despite having raised HDL-C. Prescription products that had combined niacin with a statin (Simcor, Advicor) were discontinued in 2016.

And now, almost every known drug is being tested for COVID-19 benefits, including known antivirals and repurposed other drugs (and not just drugs – vitamins D and C are being evaluated, too). Hydroxychloroquine – an anti-malarial with other approved treatment indications – has its champions in the COVID-19 arena (“It works on my patients.”), but to date, placebo-controlled clinical trials have shown no evidence that it prevents people from contracting the disease if exposed, no evidence for a faster recovery among those afflicted, and no significant reduction in the percentage of COVID-caused deaths. There are serious adverse reactions (heart, liver, kidney), known to be associated with this drug. There are more trials ongoing, some of which may indicate a benefit, but until there is a clear consensus, doctors are advised to not prescribe this drug for this indication, but because it is approved for other indications, doctors have the option of going “off-label” and prescribing it for COVID, regardless. Again, science is real, science is also slow, and sometimes science takes detours.

Alcohol: What is Moderation?

“Correlation does not imply causation.” Simply put, for two variables if both change, one cannot simply conclude that there is a cause-and-effect relationship between the two. Back in the late 1980s, alcohol, and more specifically, red wine, got a health claims boost from the “French Paradox,” an observation that the French, while known for consuming a butter- and cheese-containing diet high in saturated fats, had a lower than expected incidence of heart disease. This branched into two sets of putative health claims: A) That moderate consumption of alcohol was healthier than not drinking any; and B) that chemicals in red wine had a health benefit separate from the alcohol content.

For alcohol beverages, "Proof" is
2X percent. 'Hard liquor' products
tend to be 80 to 100 proof, labeled as
such, whereas wine and beer are labeled
percent alcohol content.

The observation about alcohol in any form, i.e., wine, beer, spirits, got support from what is described as a “J-shaped curve”, meaning that the relationship between alcohol and cardiovascular or all-cause mortality was not a straight line – with more drinking linked to more deaths – but rather a curved line the lowest risk at a modest alcohol intake, higher risk at zero alcohol intake, and ever-increasingly higher risk at higher and higher intakes (visually, the line resembles an aslant letter “J”). The “sweet spot” (lowest risk) looked to be around one-half to one drink per day.

Red wine contains proanthocyanidins, large molecules that contribute to the astringency of wine. Red wine also contains resveratrol, a small molecule upon which huge health claims were heaped. All sorts of health claims were made for resveratrol dietary supplements, even though the ingredient in question was being extracted from Japanese knotweed rather than grapes. Whilst positive results were demonstrated in animal models, in the end, human trials showed no benefits for lifespan, anti-cancer, anti-dementia, and so on. There was a lot of hullabaloo about resveratrol-like compounds as drugs, but that petered out. The proanthocyanidin story was latched onto by proponents of other natural sources of these compounds, leading to some positive-finding research and a lot of market hype for dark chocolate, blueberries, purple grape juice, and so on. Research on this is still a work-in-progress. Newest thinking is that while proanthocyanidins have antioxidant activity, this is not the mechanism of action.

Back to alcohol. Clearly, there are non-benign consequences of excessive drinking, defined both as a high average per week and occasions of binge drinking, the latter defined as five or more drinks for men and for or more for women. The Centers for Disease Control and Prevention (CDC) estimates that alcohol consumption accounts for approximately 100,000 deaths annually in the United States. That includes motor vehicle fatalities, drownings, suicides and homicides, liver cirrhosis and at least seven types of cancer. Excessive drinking also contributes to non-fatal negative consequences (injuries, arrests, home violence…). As to the alcohol “J-shaped curve,” it turns out that in many cultures, when compared to not drinking at all, modest amounts of alcohol consumption tends to be associated with many risk-lowering behaviors, such as less absence of obesity, more exercise, better diet and being non-users of tobacco. Non-drinkers can also have mental and physical illnesses that led them to never starting to drink in the first place, or else are non-drinkers now because of past illness. Either way, their non-drinking could contribute to the higher incidence of disease and death of non-drinkers that had nothing to do with any purported benefits of modest drinking.   

All this leads up to the fact that the Dietary Guidelines for Americans, a document that is updated every five years, is about to revise downward the definition of moderate consumption of alcohol. Below, a summary of the proposed guidelines for consumption of alcohol-containing beverages. It remains to be seen whether lobbying by the alcoholic beverages industry will lead to a restoration of the current definition of moderation – for men – as up to two drinks per day, of if this downward revision will stick. Draft wording: A) Do not begin to drink alcohol or purposefully continue to drink because you think it will make you healthier; b) If you drink alcohol, at all levels of consumption, drinking less is generally better for health than drinking more; and C) For those who drink alcohol, recommended limits are up to one drink per day for both women and men.

Different countries, different definitions of ‘moderation.’ Back in the 1950s, France recommended that people limit themselves to no more than one bottle per day. Currently no more than two drinks a day for both men and women, recently changed from three and two.

Folate and Folic Acid

Folate is a B-vitamin that occurs naturally in plants – more in some than others. Folic acid is a synthetic compound incorporated into multi-vitamins, dietary supplements and used to fortify foods; once absorbed it is converted into folate. Starting about 20 years ago, the United States decided to mandate fortification of wheat flour and other grains with folic acid in order to reduce the risk of infants being born with spina bifida and other neural tube defects (NTDs). In effect, the decision was made to increase folate in 350 million people to prevent an estimated 1,000 to 1,500 birth defect births per year. At the time, concerns were raised that this folic acid fortification might have unknown health-positive and health-negative consequences, the latter including an increased incidence of cancer. So far, most of this has proven to be not true.

In general, beans, nuts and seeds are good sources of food folate, as are dark, leafy green foods (spinach, etc.) and cruciferous vegetables. Animal liver is a great source, but animal meat, dairy and eggs, not. People who adhere to a vegetarian or vegan diet should have no worries about getting adequate folate from food, although there are other vitamins for which a general-purpose vitamin/mineral supplement is recommended. Currently trendy diets need to be examined for nutrient deficiencies. A ‘keto’ (ketogenic) diet avoids carbohydrates, but if it contains enough in the way of leafy green vegetables it should not shortfall the recommended intake of food folate. Exceptions are any women who might become pregnant, as the recommendation is to be consuming 600 micrograms of folate as folate and folic acid before and during the pregnancy. “Gluten free” diets can lead to folate deficiency, especially if people are replacing wheat-based foods with alternative sources of carbohydrates. Here too, consider a general-purpose vitamin/mineral supplement.

Worldwide, there were about 300,000 live NTDs per year before any country required folic acid fortification. The U.S. and Canada were the first countries to implement fortification in early 1998. For the sixty-some countries that now require fortification of wheat flour, and/or corn meal or rice, the incidence of NTDs has dropped by 25 to 50% (higher in countries that started with low folate intake from diet). The reasoning for fortification over advising women who became pregnant to start taking a folic acid supplement was they the risk for development of neural tube defects is greatest in the first few months of pregnancy – a time when women may not even be sure they are pregnant.

In the U.S., the decision to fortify food with folic acid resulted in roughly a 50 percent increase in total folate (naturally occurring from food plus folic acid). There were hopes among researchers that requiring fortification of foods, and thus increasing folate status in everyone, not just women of child-bearing age, would also have benefits for cardiovascular and mental health. The latest reviews of evidence report no change cardiovascular disease in general, but a modest decrease in the risk of stroke in people who already had pre-existing cardiovascular disease. Evidence for the last came from trials with folic acid supplementation in amounts higher than were achieved just from the food fortification program. In the arena of mental health, there are not enough human trials to determine if there are any benefits toward mild cognitive impairment, dementia in general or Alzheimer’s disease. One promising result is evidence that adequate folate status during pregnancy reduces the risk of the child developing autism.  

As for the whole cancer thing, long-term intake of insufficient amounts of folate appears to increate the risk of several types of cancer, including breast, colorectal, lung and prostate cancer. Although there were theories that folic acid fortification of foods would increase risk of cancer, by promoting growth of preneoplastic lesions, this turned out not to be true. Even supplementation in amounts far in excess of what would be achieved by food fortification did not increase cancer risk – but with one exception – prostate cancer. Multi-year, high-dose trials with folic acid supplements resulted in a 15 to 25 percent increase in prostate cancer compared to unsupplemented control groups. 

The Wikipedia article Folate elaborates on information presented here. Major population centers not requiring mandatory fortification include China, India, the European Union and Russia. Instead, these countries have public health education programs recommending to women that a folic acid dietary supplement be consumed starting months before becoming pregnant and continuing through pregnancy. The U.S. and other countries that now require fortification found that health education alone was not sufficient.

Death by Exercise

Sudden cardiac death – as in the college-age basketball player or the hyper-fit triathlon participant – tends to make the news. As it should. Newsworthy death while exercising provides every non-exerciser with rationale for not exercising. “See” they say, “this person was an avid runner [cyclist, swimmer] and dropped dead at 40.” The contrarian point being that the endurance sports that are supposed to protect against heart disease sometimes appear to do just the opposite.

There is a wisp of truth to this observation. Estimates are that just under one person per 100,000 participating in a marathon, or 1.5/100,000 participating in a triathlon will die during or immediately after the event. Figure a collective three million participants in these types of races and that comes to maybe 30 to 40 deaths per year. There are fuzzier estimates of perhaps one sudden death per every million exercise events for other forms of vigorous exercise. So, the true answer is yes, exercise can kill the physically fit, but no, not a risk factor worth avoiding exercise entirely.

Internet image portraying a man having a heart attack while exercising.

There is more truth in the observation that exertion by the physically unfit can result in fatal cardiovascular events. The classic case is the middle-aged office worker who drops dead shoveling snow while attempting to clear the driveway and get to work. Contributing factors include the fact that blood pressure peaks in the morning a few hours after waking up, and the fact that exertion in cold weather constricts arteries, further adding to heart stress. Snow removal related heart attacks frequently occur in women and men with no known pre-existing heart disease.

Exercise can also result in accidental death. In the U.S., walking, running, bicycling, swimming, boating and winter sports add up to about 10,000 deaths per year. Subtract half who are either children or are adults under the influence of alcohol (as in walking or riding a bike home from a bar, at night), and it’s still a big number. But the total pales compared to the 2,800,000 total deaths per year, of which many are premature cardiovascular deaths brought on by a lifetime of inactivity.

The good news is that benefits from even modest amounts of exercise are becoming clearer. The American Heart Association recommends adults get at least 150 minutes per week of moderate-intensity aerobic activity or 75 minutes per week of vigorous aerobic activity, but notes that even a few minutes per day was better than nothing! Studies have reported the greatest improvement for modest exercise compared to no exercise at all, and diminishing but still cumulative returns for progressively more exercise. A recent article in the Journal of the American Medical Association reported that endurance fitness was a better predictor of good cardiovascular biomarkers (cholesterol, etc.) than strength.

The theory that aside from injuries, over-doing exercise may cause more harm than good has been disproven. A science journal article reviewed studies of longevity of elite athletes. Athletes from endurance sports had 3-6 year longer life spans than the general population. The authors cautioned that elite athletes may by genetically different from the population as a whole, with both their abilities and lifespan being consequences of their genes rather than one causing the other. A review article encompassing 48 published studies confirmed that people doing as much as 7-14 hours per week of moderate to vigorous exercise were had a 15 percent lower mortality risk than those doing only 1-2 hours per week, with no hint that the benefit fades toward the high end.  

There is a non-fatal problem with exercise – it is potentially addictive. As one well-known fitness expert author put it, “…people reduce their lives to fitness routines, training as many as 40 hours a week. That the effort may wreck marriages and compromise immune systems isn’t even relevant. To these people – demographically a diverse lot – exercise is addictive. The more the body gets, the more it wants. In return, the drug of exercise infuses the swimmer, cyclist and runner with two powerful illusions: that he/she is escaping the horrible, and progressing toward the divine.”

Why do We Sweat?

If we were any other species of mammal, including our closest relatives, the great apes, we would not perspire, and the deodorant industry would not exist. Humans perspire a lot; horses a bit. Dogs (and wolves, coyotes, fox, lions) pant. Prey species such as deer are fast in a sprint, but not equipped for long distance running without overheating. It’s us, the hairless ape, that is unique.

The major function of perspiration is to cool. When water on skin evaporates there is a transfer of huge amounts of heat away from the skin. Cooling of the skin’s surface cools blood circulating underneath, which cools the body as a whole. Panting, while not as effective, serves the same purpose. Kangaroos, which neither sweat or pant, lick their forelimbs, achieving evaporative cooling that way.

No evaporation, no cooling. Hence the truth behind “It’s hot, but it’s a dry heat.” In humid weather, we still attempt to cool by sweating, but the moisture soaks our clothing and drips off without the benefit of evaporation. (Standing in front of a fan helps.) In passing, worth a mention that a traditional sauna practice reverses the heat exchange process. Sauna is very dry heat, so a person can be comfortable in temperatures of 140-180 degrees Fahrenheit, versus 110 to 115 degrees tops for a steam bath. “Löyly,” the practice of throwing water on superheated stones during a sauna, converts the water to steam, which then condenses on cooler surfaces, such as skin. The condensation process transfers heat to the skin. The intense wave of heat experienced about 30 seconds after water hits hot stones is the opposite of evaporative cooling.

What is sweat? First, it is initially sterile, and hence not initially smelly. However, our skin is inhabited by billions of moisture-loving bacteria. The smells we associate with sweated up clothing are from the happily replicating bacteria that consumed our skin gland secretions for food and produced their own smelly waste products. Men and women have different mixtures of skin bacteria, and thus different smelling sweat. Interestingly, some studies show that homosexual women and men are more sexually attracted to the smell of same-sex sweat, versus heterosexual women and men who are more turned on by opposite sex sweat, but whether this is genetic or driven by one’s sexual orientation is not known. For some people, skin harbors Propionibacteria which product propionic acid, a compound that smells a lot like the chemically related acetic acid in vinegar. Time to wash those clothes and take a shower!       

Back to sweat. Sweat is 99.9 percent water and one-tenth of one percent minerals and organic compounds. Sodium makes up the majority of the minerals, then potassium and small amounts of calcium, zinc, copper and iron. Sports performance researchers have looked into heat adaptation. Results suggest that sweat at the end of a long, hot day has much the same composition as in the morning. However, over days in a hot environment, mineral content decreases by as much as a third. Thinking is that the body has adapted to conserve minerals while still managing evaporative cooling.

Other causes of sweating are emotional sweating, which can include sweaty hands, not seen during thermal-triggered sweating. A third cause is a reaction to eating very spicy foods.

Sports drinks (Gatorade, Powerade) are a multi-billion dollar industry based on the theory that modest amounts of minerals (primarily sodium, but some potassium and magnesium), plus calories will have a performance benefit over water during a prolonged period of exercise. There is a kernel of truth there. Given water to drink, actively exercising people will drink less than the water being lost to perspiration. And that’s generally okay, as athletic performance begins to suffer only after two percent weight loss. A salty-tasting, slightly sweet beverage will cause people to drink more compared to plain water. More is not necessarily better, just more. The sodium provides no performance benefit. The carbohydrates do provide usable energy, but that only really matters for hours of strenuous exercise.

People in the U.S. consume too much sodium. Our kidneys dump the excess in urine, but the effects of high sodium consumption include hypertension and higher risk of stroke and coronary heart disease deaths. National surveys estimate that average adult consumption is 3,400 milligrams per day, whereas recommendations are to consume less than 2,300 milligrams, and  1,500 milligrams per day is defined as an adequate amount. Only for people doing prolonged, vigorous exercise, say a hundred mile-bicycle ride, might there be a benefit for calorie-containing beverages or snacks during the event. That’s for energy. After the event, normal foods and beverages will replenish whatever minerals were lost.  

Rise and Fall of Vitamin E

Vitamin E was the vitamin D of the 1990s – good for whatever ailed you. Claimed benefits led with cardiovascular disease and cancer, but piled on with macular degeneration, pregnancy, dementia and other significant diseases. With no apparent concerns about safety, there was a race up to mega-dose amounts being widely sold as non-prescription dietary supplements. Vitamin E even ended up in skin care products, with claims for helping hear scars and burns, in shampoos with claims for healthier hair. Things changed.

Worldwide, government organizations are not quite in agreement on how much is recommended and what is the safe upper limit. The U.S. recommends 15 mg/day, and up to 1000 mg/day as safe. Japan recommends 7 mg/day and no more than 900 mg/day (for men, numbers a bit lower for women). The European Union recommends 11 mg/day for women, 13 mg/day for men, and no more than 300 mg/day for both sexes. Actual consumption is less. Worldwide, median dietary intake is 6.2 mg/day for alpha-tocopherol.

Alpha- and gamma-tocopherol are the two most common
forms in plants. Alpha- has three methyl (CH3) groups on
the leftmost ring of carbon atoms while gamma- has two.
The arrows point to the difference. (Internet download).
Click on image to make larger. 

Note that intake number is for alpha-tocopherol. “Vitamin E” is actually a collection of eight chemically related but distinct molecules: alpha-, beta-, delta- and gamma-tocopherol and the same four designations as tocotrienols. Leafy green vegetables are predominately alpha-tocopherol and seed oils gamma-tocopherol (with exceptions). Palm oil is higher in tocotrienols than tocopherols. Although gamma-tocopherol is the highest percentage dietary form, our bodies create a blood transportation protein that preferentially binds only to alpha-tocopherol, making it the majority molecule in blood and organs. It is also by far the most potent antioxidant of the eight. So, “vitamin E” is usually taken to mean alpha-tocopherol, with a minor contribution to alpha-tocopherol equivalents from the other forms.     

The popularity of naturally sourced or synthetic alpha-tocopherol as a dietary supplement began with a juxtaposition of theory and observation. Vitamin E is thought to function as an antioxidant. Oxidation is all about oxygen (duh!). Normal biological processes create oxidating compounds, also referred to as free radicals, that need to be neutralized, else cell damage takes place. One of the theories of aging is that oxidation causes cumulative damage over years and years, leading to what we identify as the diseases of aging. Our bodies create antioxidants and also use vitamin E (and vitamin C, and selenium) as antioxidants. These nutrients, alone and in combination, have been heavily researched for disease prevention. With mixed results.

Observational studies tracked the lifestyle habits and health histories of tens of thousands of nurses and doctors. Results showed that those who on their own either consumed more vitamin E because of food choices, or had chosen to take vitamin E dietary supplements, had a one-third lower risk of heart disease. Publicity from this let to roughly 50% of nurses and doctors to use vitamin E as a dietary supplement. Millions of Americans followed the examples of their health care professionals. Sadly, subsequent clinical trials that enrolled people to either vitamin E or a placebo and tracked them for years were not as consistently positive. Collectively, there appears to be a modest reduced risk for heart attack, no benefit for risk of stroke, and no change in all-cause mortality. With hindsight, in the initial research, health professionals who had decided to consume vitamin E supplements may have made other lifestyle decisions that promoted good health. It is an example of correlation not necessarily reflecting causality.

Research for other diseases has also had mixed results. An antioxidant combination appears to slow progression of age-related macular degeneration, but vitamin E alone has not been evaluated. There has not been enough research for any recommendation on effects on dementia, or on Parkinson’s disease. Vitamin E in combination with vitamin C was not seen as beneficial for pregnancy outcomes. Cancer results are mixed depending on type; also some evidence that while low amounts of a supplement are beneficial, higher amounts actually increase risk (a similar cross-over effect seen for higher amounts and cardiovascular disease).

Despite the widespread belief that topical vitamin E can help with burn and wound healing, rigorous clinical trials belie that conclusion. There is no useful evidence supporting the idea that a vitamin E containing shampoo or conditioner improves hair health.

Cumulatively, doubts about efficacy and concerns for subtle negative effects of higher doses led to a massive decline in the percent of people buying vitamin E.  What to do in the face of all this ambiguity? Eat more fruits and vegetables (always an easy recommendation). Most daily multi-vitamin/mineral products will include 100% of the Daily Value for vitamin E, which can be seen as do-no-harm. Beyond that, the merits for a vitamin E as a supplement are suspect, and this is definitely not a more-is-better situation.

The Wikipedia article on Vitamin E has references for most of this content.

Ticks: Lyme, Anaplasmosis, Babesiosis

From left to right: larvae, nymph, adult male, adult female.
Nymphs and adult females are the vectors for human infection.
Ticks get on your shoes, socks or legs when you brush against
vegetation. Ticks do not drop from above. The CDC website
recommends chemical repellants, also how to do a tick check
and how to wash and dry clothes to kill ticks.

June and July are the prime months for contracting a tick-borne disease. During these months the vector is the nymph stage, which is about the size of a poppy seed. There is a lessening incidence in August, September and further into fall and winter, as the vector becomes the more easily seen adult female tick (the size of a small apple seed), and also because people spend less time outdoors with the onset of colder weather.

An observation here: the term 'bite' is not descriptive. If not detected, a nymph will latch on for 3-4 days for a blood meal before dropping off; adult females stay attached for 7-10 days. Adult males are not on you for a meal. Rather, they are wandering around looking to find and fertilize a female. This meet-and-mate part of the tick's life cycle is the reason that deer are integral to a region harboring a serious tick disease problem. Small mammals (mice, chipmunks, etc.) are vectors for the larval and nymph stages to become infected, but a large mammal species such as deer is essential for the mating and final blood meal that allows the fertilized adult female tick to lay up to 3,000 eggs.    

Lyme, Anaplasmosis and Babesiosis are the big three for New England, but the full count for tick-borne diseases now overtops a dozen. More information on tick-vector diseases can be seen as the Centers for Disease Control website: http://www.cdc.gov/ticks/. The CDC has great information on the tick diseases, and also on practical matters such as how to avoid getting bitten by a tick, and what to do once you have been bitten.

Lyme starts subtle. If the stricken person missed the actual bite, then the first sign is often but not always the signature "bull's eye" rash. Moderate fever, chills, fatigue, muscle ache and a headache may accompany the rash. Only months after the rash and the initial set of symptoms are gone is there a possibility that really bad consequences set in: arthritis, partial facial paralysis, meningitis, limb weakness, and so forth.

Anaplasmosis is not subtle. The symptoms are more akin to being run over by a car, having it circle around to hit you again, and then one more time to park on your head. Some 7 to 10 days after the bite the symptoms arrive all at once: extreme fatigue, high fever, uncontrollable shivering alternating with profuse sweating, night sweats, headache, nausea, abdominal pain, loss of appetite, weight loss, muscle pain, cough, mental confusion, and extreme fatigue. Really extreme.

Babesiosis is not subtle. Symptoms, arriving 10-30 days after being host to a tick, are akin to those of Anaplasmosis, plus it destroys red blood cells and platelets. From the latest data published by the CDC, Massachusetts has more cases of Babesiosis than any other state.

The CDC uses the term "malaise," but this does not convey the soul-crushing lethargy of either of these full-speed infections. Not everyone exhibits all the symptoms, and many of these symptoms overlap with what people expect if they have the flu, causing many people to delay seeking a medical evaluation, or doing so, getting a misdiagnosis.

Actually, these days, diagnosis and treatment are straightforward. Do you have some or all of that litany of symptoms, especially fever and fatigue? Were you in any place a week or four ago where there might have been ticks? That's it. A blood sample will be taken, but especially early in the course of the infection the test results can be false negative (says you don't, but you do). Standard medical practice is to start antibiotic treatment immediately. Treatment should never be delayed until the lab results are back. These days, there is an assumption that more than one disease is transmitted from the same tick, so for Babesiosis, doctors may prescribe multiple antibiotics.

Neither casual contact nor intimate sexual contact will pass on any of these diseases, but receiving a blood transfusion has been a confirmed vector. There are no laboratory screening tests to verify that donated blood is not infected. 

Not treating infections in a timely fashion can have very serious consequences. Delayed treatment may require hospitalization and intravenous antibiotics. Especially in older or immuno-compromised people there are risks of compromised breathing, kidney failure, nerve damage and death. A practical point - your guests can contact a tick disease here, then travel to regions where doctors may not have tick disease awareness. Your parting words might include "Safe travels, and if you develop a rash or become ill, tell your doctor you were in tick territory."

Anaplasmosis - the Other Tick Disease

There is a new kid in town - Anaplasma phagocytophilium. This bacterium is carried by the same deer ticks that bring us Lyme disease. Prime time for tick diseases is May through August. The symptoms are different but the course of action is the same - get diagnosed, get treated.

Lyme disease signs and symptoms start subtly. If the stricken person missed the actual bite, then the first sign is often (but not always) the signature rash. Fever, chills, fatigue, muscle ache and a headache may (or may not) accompany the rash. Only after weeks to months after the rash (which does not always occur) and the initial set of symptoms (ditto) are gone is there a possibility that the really bad consequences set in: arthritis, partial facial paralysis, meningitis, limb weakness, and so forth (or not).

In stark contrast, the symptoms of anaplasmosis are more akin to being run over by a car, having it circle around to hit you again, and then one more time to park on your head. Or in gamers' terms, "All your base." [Look it up.]

Some 7 to 10 days after the bite the anaplasmosis symptoms arrive all at once: extreme fatigue, high fever, uncontrollable shivering alternating with profuse sweating, night sweats, headache, nausea, abdominal pain, loss of appetite, muscle pain, cough, mental confusion, and extreme fatigue. Really extreme. The Centers for Disease Control (CDC) uses the term "malaise," but this does not convey the soul-crushing lethargy of a full-speed Anaplasma assault.

Not everyone exhibits all the symptoms, and many of these symptoms overlap with the flu and other diseases, either causing many people to delay seeking a medical evaluation, or doing so and getting a misdiagnosis.

Actually, these days a diagnosis is straightforward. Do you have some or all of that litany of symptoms, especially fever and fatigue? Were you in any place a week or two ago where there might have been ticks? Do you have any symptoms which hint you may have something else? If not the last, that's it. A blood sample will be taken, but early in the course of the infection the test results can be falsely negative (results say you don't, but you do). Standard medical practice is to start antibiotic treatment immediately. Treatment should never be delayed until the lab results are back. Standard treatment is the same as for Lyme - two weeks of doxycycline.

Not treating an Anaplasma infection in a timely fashion can have serious consequences. Especially in older or immuno-compromised people there are risks of compromised breathing, kidney failure, nerve damage... Treatment may require hospitalization and intravenous antibiotics. Deaths are rare (less than one percent).   

Anaplasmosis does not appear to be casually contagious. As a blood-borne disease it could in theory have the same vector as HIV/AIDS, but there is no mention in the science literature of transmission via sexual contact. There are confirmed reports of infection from blood donations, and in theory the same risk would apply to organ transplant recipients. Currently there are no good blood or organ donor screening tests.

As noted, Anaplasma is carried by the same tick as Lyme disease. Reported cases of Lyme number about 30,000 per year. This is accepted as an undercount, as many people do not seek medical assistance, and so were never diagnosed. Others sought medical help and were misdiagnosed (keep in mind the false negative problem with blood tests also applies to Lyme). And finally, some were correctly diagnosed but not reported to the appropriate health agency. With the same caveats in mind, the anaplasmosis report for 2010 (the latest year with national data) was 1,761 cases. Hotspots for both diseases are the Northeast and the upper Midwest.

 NEWS FLASH: On August 18, 2013, the Centers for Disease Control revised its estimates of numbers of new Lyme disease cases per year from 30,000 to 300,000. This 10X increase was the result of survey blood testing laboratories for numbers of positive blood tests, versus the old method of depending solely on reports from physicians. All physicians are supposed to report all confirmed or suspected Lyme disease to the CDC, but obviously, this has not been true. It is likely that other tick borne diseases are under reported.

More information on tick-vector diseases can be seen as the CDC website: http://www.cdc.gov/ticks/. The CDC has great information on the tick diseases, and also on practical matters such as how to avoid getting bitten by a tick, and what to do once you have been bitten. You can even download a 21-page handbook: Tickborne Diseases of the United States. Another site with a good pictoral of the life cycle and high risk months is www.aldf.com/DeerTickEcology.shtml.       

One small, small benefit from having survived an anaplasmosis infection is that if someone asks how you are, and you answer "I've been worse," you are telling the truth.

In addition to Lyme and Anaplasma, deer ticks may also transmit babesiosis (a parasite disease) and Powassan virus. Babesiosis is rarer than Anaplasma, and Powassan is extremely rare. Other diseases are transmitted by other tick species in other regions of the country. Visit the CDC website for details.

Deer Ticks and Lyme Disease

This is a reposting of a 2011 article, revised, because we are once again in Lyme disease season. See also the anaplasmosis article posted in August 2013 (another tick borne bacteria).

NEWS FLASH: On August 18, 2013, the Centers for Disease Control revised its estimates of numbers of new cases per year from 30,000 to 300,000. This 10X increase was the result of survey blood testing laboratories for numbers of positive blood tests, versus the old method of depending on reports from physicians. All physicians are supposed to report all confirmed or suspected Lyme disease to the CDC, but obviously, this has not been true.

Why “Lyme?” Names can be for symptoms, the discovering doctor’s name, a defining population or a place. The villages of Old Lyme and Lyme, in Connecticut, combined population under 10,000, were the epicenter of an unknown disease in 1975. The story starts with a mother. Polly Murray had two children diagnosed with juvenile rheumatoid arthritis. As she commiserated with other parents of children with JRA, she was struck by how common this supposedly rare condition had become in their small community. Murray complained to the state health department, thinking perhaps there was an unknown pollution problem. 

Her efforts and her list of 39 children with similar symptoms brought in Dr. Snydman of the health department, who brought in rheumatology expert Dr. Allen Steere from Yale University. Dr. Steere made the connection to the possibility of tick-borne bacterial disease. The bacteria responsible for Lyme disease is Borrelia burgdorferi.  Lyme Arthritis, later renamed Lyme disease, could have as easily been Murray’s disease or Steere’s disease.

A tick’s life has three stages played out over two years. Confusingly, people describe deer ticks as the size of a typed dot, a poppy seed, or an apple seed. All descriptions are true. Uninfected larvae hatch from eggs in late spring, hoping to latch on to a field mouse. One blood meal is all they are after, but if the mouse host is infected, so becomes the tick. The larval tick morphs into the nymph stage and forgoes feeding off animals through fall, winter, and early spring. Come May, these poppy seed sized, possibly infected nymphs are hanging out on ground level vegetation, hoping for a mouse or bird to brush by. 

Ground level gardening work puts humans at risk. Most human infections are from nymphs, contracted May through August. The nymph stage is also after only one modest-sized blood meal, so it does not stay attached for long. Gorged, the ticks drop off the host to the ground and morph into adults. Come fall, these adults climb tall grasses and shrubbery to pose there legs outstretched, hoping to latch onto a passing deer. Once on board, females adult settle in for their third and last blood meal, getting the protein they need to make eggs, while males wander around to find and mate with the females. It helps to visualize each deer as a singles cruise ship. 

Females overwinter at ground level, then in the spring lay 1,000 to 3,000 eggs to start the cycle over again. Some adults miss latching onto a deer in the fall, overwinter as adults, and are then out in spring for a last chance at mating and a blood meal (and an infection). More information is available from the American Lyme Disease Foundation [www.aldf.com] or the Centers for Disease Control [http://www.cdc.gov/ticks/]. ALDF has a good pictoral of the life cycle and high risk months at www.aldf.com/DeerTickEcology.shtml.

Trans-species diseases are evolution’s biggest wild card. In theory, diseases are not supposed to eliminate their hosts. Or rather, those that do disappear from the global gene pool along with their hosts – game over. The norm is more like disease, resistance, mutating disease, mutating resistance, ad infinitum. Both survive. More rarely, a disease jumps species.  American chestnut trees, elms and dogwoods all succumbed to non-native diseases. Sheep scabies passed through cows to give us the gift of mad cow disease. The influenza virus drifts across humans, pigs and ducks, wreaking havoc as it mutates. Natural hosts for Lyme disease bacteria are field mice and whitetail deer. Humans are just collateral damage.

No deer means no deer ticks, means no Lyme disease. Extensive land clearing, farming and hunting forced the U.S. whitetail deer population to under half a million a century ago. Subsequent establishment of controlled hunting seasons, loss of natural predators, plus abandonment of many eastern farms to reforestation has resulted in an out-of-control population exceeding twenty million deer. 

While wildlife biologists consider 10 deer per square mile a sustainable population, many northeastern states are seeing 40 to 60 or higher per square mile in rural and suburban areas. Lyme disease cases in the U.S. increased from 10,000 in 1992 to 30,000 in 2012. Of that last total, more than two-thirds were in the New England and mid-Atlantic states. One could argue that not going into the woods is an answer, but as any gardener, landscaper or farmer knows, the deer have come to us.

Water - How Much to Drink?

How much water to drink? The short answer is enough that you pee enough.

Our body's water content is strongly regulated to stay very close to normal hydration. There is no such thing as chronic dehydration unless there is also chronic water rationing. Enough water is enough - more is not better - and too much has risks.

Water comes from beverages, water content of food, and the metabolic water created by converting food to energy (example: sugar metabolized to carbon dioxide and water). Water loss from breathing, from sweating, and as water content of feces are not under strong physiological control. Instead, urine volume is regulated. Normal urine production is 1,200 to 2,000 ml/day (think 1 to 2 quarts). Drinking more than needed increases urine production - can be 10 liters a day or more.

Urine production cannot drop to zero because that is how our bodies dispose of metabolic waste products. Our kidneys can concentrate all the waste into an disposal volume of 500 ml/day, but not much smaller. Drinking more does not dispose of more waste - it just dilutes the same amount into a larger volume of urine.

ADEQUATE INTAKE

There is debate on what is considered Adequate Intake (AI). The U.S. government, through the Dietary Reference Intakes (DRIs) for water, published by the Institute of Medicine in 2005, decided that men ages 19 and older should consume 3.7 liters (125 ounces) per day, and women 19 and older should consume 2.7 liters (91 ounces) per day.

These numbers refer to total water intake (TWI), which includes beverages and water content of foods. The typical split is a tad under 80% from beverages and a tad over 20% from food. Hence, men and women should be drinking 100 and 73 ounces, respectively. The reality here is that the IOM wasn't sure how much water is really needed, so it sort of rationalized that the average intake is an adequate intake.

Europe disagrees. The European Food Safety Authority decided in 2010 that an AI for men is 2.5 L and for women 2.0 L. The World Health Organization likes 2.5 L/day for men and 2.2 L/day for women. But keep in mind that the WHO assumes average weights for men and women as being 154 and 128 pounds, whereas the current averages for U.S. adults are 196 and 166 pounds. Adjusting for weight would put the WHO recommendations closer to the U.S. numbers.

A old rule of thumb that tries to take into account a need for more water with an increase in calories being consumed (because physical work or exercise requires more calories and needs more water to compensate for sweating and breathing losses) is to estimate water needs as 1.5 ml per calorie intake from food and drink. By this math a sedentary person taking in 1800 calories would need 2.7 L, whereas a larger and/or more physically active person consuming 3000 calories per day would need 4.5 L.

CONSEQUENCES OF INADEQUATE INTAKE

There is no evidence that drinking more reduces risk of dying. This from a study that tracked 12,650 people for 6.7 years. What it did was look at how many people died in the lowest 25% for water intake (they averaged 1.75 L/day) and compared the three higher quartiles to the lowest. No statistically significant differences among the four groups.

Higher total water intake does reduce the risk of getting kidney stones. Higher total water intake also reduces the risk of exercise-induced asthma attacks.The evidence for weight management is iffy. Drinking water 30 to 60 minutes before a meal reduces calories eaten in that meal. There is evidence that when water is substituted for calorie-containing beverages, total calories per day decreases. In a large epidemiological study, people who drank more water weighed less. But as water consumption might co-occur with other lifestyle choices, it is not clear if the water intake was responsible for the weight difference.

Evidence for health benefits beyond those mentioned above is either weak or contradictory. Dehydration will increase the risk of constipation, but for adequately hydrated people, drinking more water will not alleviate constipation. The idea of more hydration improving skin health has not been proven. There is inconsistent data for more water lowering the risk of bladder cancer, colon cancer or urinary tract infections.

EXCEPTIONS TO THE RULE OF THE BODY MANAGING HYDRATION

Short-term, dehydration and overhydration are easily achieved, with potential for serious consequences. People doing vigorous physical activity can lose a quart an hour via a combination of perspiration and the moisture of exhaled air. A review of 2,135 athletes who had completed endurance events found that 50% had experienced more than a 3% weight loss. Given that we are 60-70% water, that is roughly 5% water loss. It is well documented that body weight loss of more than 2% is known to compromise exercise capacity and mental function.

The same study reported that 11% were overhydrated. i.e., weighed more at the end of the event than at the beginning, and one-tenth of those had symptoms of hyponatremia (low blood sodium). When so much water is consumed that sodium in the blood is diluted, water moves into cells, resulting in swelling. Puffy hands, ankles and face seem harmless, but brain cells also swell, increasing pressure. Symptoms progress from headache and nausea to stupor, seizures and death. Sports drinks contain some sodium, but not enough to prevent hyponatremia if consumed in excess.

For some people, vigorous exercise shuts off urine production even if they are overhydrated. This can persist for hours after exercise ceased. If under the mistaken belief that they are dehydrated because they are not urinating, and then they drink more, this exacerbates the problem. It is essential to do a body weight check before an endurance event and at the end. If weight has gone up, do not drink anything. If weight has gone up a lot, get to medical care quickly.

WATER AND BODY WEIGHT

As easy way to understand the impact of water on body weight is to weigh oneself just before going to bed and second thing in the morning (after a morning pee). Most people find they are 1.5 to 3.0 pounds lighter in the morning. If that were true body weight loss it would represent 5,000 to 10,000 calories expended (using the loose rule of 3,500 calories per pound), whereas the real estimate of calories burned while at complete bed rest for 7-8 hours is more on the order of 500 calories. So most of that weight loss is from water as urine, breathing out moist air, and water loss through skin. That last occurs even it not noticable as perspiration.

The intestinal tract contains water. Food takes several hours to get from the mouth to the start of the large intestine. At this point the water content is quite high, as in addition to the water content of the food and whatever beverages were consumed with the food, the salivary glands and stomach and small intestine digestive secretions contribute at least a quart more. Once into the large intestine more than 90% of the water is recovered/resorbed, but at any time the large intestine contains 2.5-5.0 pounds of feces, with 75%-90% of that being water.

Normal bowel movements are about a half-pound a day of which about 70% is water, but severe, prolonged diarrhea can be dehydrating because the large intestine did not have an opportunity to recover water.  

Age and Peak Athletic Performance

Sarcopenia - age-related muscle loss - becomes more common

and more severe after age 60, but even for 80 year olds a supervised

program of resistance exercise can add strength and improve quality of life

Peak athletic performance is reached at age 30, with remarkably little decline for the next ten years. After 40 there is a slow, steady decline to age 60, accelerating thereafter. The mid-life decline is a consequence of less oxygen being delivered to muscles; the late-life decline to a complex web of less oxygen delivery plus loss of muscle mass, compounded by disuse, obesity and osteoarthritis. But there is hope.

At the direct physiological level, theories span loss of function of nerves that control muscle movement, less oxygen uptake in the lungs, decreased oxygen delivery by blood, lessened availability of fuel, and poorer fuel use efficiency. While lung function can decline with age, especially in smokers or people with occupational exposure to airborne chemicals, the main cause is ever-decreasing oxygen delivery. With age there is a decline in maximum heart rate (roughly estimated as 220 minus age), less blood volume per heartbeat and progressive loss of capillaries delivering oxygenated blood to muscle cells. 

Fuel availability and usage are not part of the problem - muscle cells have adequate access to fuel and do not require more calories to contract. This aspect, known as "exercise economy," is assessed by looking at the metabolic calorie cost of sustained submaximal exercise.

Other changes factor into sarcopenia. Beyond 60 years, sensitivity is lessened to the signals which in younger people will trigger muscle enlargement, for example, vigorous exercise or consumption of a high protein diet.

Indirect contributors to the age decline include disuse, obesity and osteoarthritis. After college age, few people have physical labor jobs or sufficient leisure time for the 20 to 30 hours of training per week needed to maintain a level of physical activity necessary for peak performance. Recovery from sports injuries take longer. Body fat, especially torso fat, is pre-inflammatory, contributing to muscle cell insulin resistance; without this anabolic signal being received, muscles shrink. Osteoarthritis has a chicken-or-egg-first relationship with fitness, as exercise slows the progression of osteoarthritis, but this disease is a major reason people stop being physically active.

Certain sports appear to contradict the "peak at 30" hypothesis, but on closer examination, may not. For many years women's swimming and tennis were dominated by teenagers. These individual-effort sports channeled young girls into early commitment and intense training. The typical result was an early-age peak followed by mental burn-out and/or career-ending physical injury. With wider access to competitive sports via Title IX, a broader pool of women athletes across a wider range of sports finds peak ability reached in close to 30 years, just like men. In the New York City marathon, women in their mid-40s are competitively close to women ten and twenty years younger.

The net result of the direct and indirect consequences of aging? For healthy, well-trained endurance athletes there is a 20 to 25% decline in performance from age 40 to age 65. Evidence comes from bicycling time trials, and 5K and 10K runs. Decline over time is faster for occasional athletes and the sedentary.

There is hope. For the approximately ten million U.S. adults who have sarcopenia, i.e., age-related muscle loss, a supervised program of resistance exercise can partially reverse muscle weakness and improve quality of life, even when started late in life. Vitamin D at 1,000 IU/day (many elderly are vitamin D deficient) has been proven to reduce the risk of injury from falls by 20 percent. Flavonoids, chemical compounds found in foods such as red wine, dark chocolate, green tea, nuts, and some types of dark-colored fruits, and are thought to contribute to artery health.

"Article Directory by Category" lists eight other health-related topics, such as recovering from donating blood (March 2011).

Death by Exercise, Marathon, Triathlon

Sudden cardiac death – as in the college-age basketball player or the hyper-fit triathlon participant – tends to make the news. As it should. Newsworthy death while exercising provides every non-exerciser with rationale for not exercising. “See” they say, “this person was an avid runner [cyclist, swimmer] and dropped dead at 40.” The contrarian point being that the endurance sports that are supposed to protect against heart disease sometimes appear to do just the opposite.

There is an iota of truth to this observation. Estimates are that just under one person per 100,000 participating in a half-marathon or marathon, or 1.5/100,000 participating in a triathlon race will die during or immediately after the event. The great majority of triathlon deaths occur in the swim phase. Figure a collective three million participants in these types of races each year and that comes to maybe 30 deaths per year. There are fuzzier estimates of perhaps one sudden death per every million exercise event for other forms of exercise. So the true answer is yes, exercise can kill the physically fit, but no, not a risk factor worth avoiding exercise entirely.

There is more truth in the observation that exertion by the physically unfit can result in fatal cardiovascular events. The classic case is the middle-aged office worker who drops dead shoveling snow while attempting to clear the driveway and get to work. Contributing factors include the fact that blood pressure peaks in the morning a few hours after waking up, and the fact that exertion in cold weather constricts arteries, further adding to heart stress (triathlon deaths in cold water probably for the same reason). Snow removal related heart attacks frequently occur in women and men with no known pre-existing heart disease.

Exercise can also result in accidental death. In the U.S., walking, running, bicycling, swimming, boating and winter sports add up to about 10,000 deaths per year. Subtract half who are either children or are adults under the influence of alcohol (as in walking or riding a bike home from a bar, at night), and it’s still a big number. But the total pales compared to the 2,500,000 total deaths per year, of which many are premature cardiovascular deaths brought on by a lifetime of inactivity.

The good news is that benefits from even modest amounts of exercise are becoming clearer. In a 2011 article in The Lancet, C.P. Wen and co-authors reported that for a multi-year tracking study of 416,175 Taiwanese adults, as little as 90 minutes per week of moderate-intensity exercise reduced the risk of death by fourteen percent. Each additional 90 minutes per week added four percent further reduction. Other studies have also reported the greatest improvement for modest exercise compared to no exercise at all, and diminishing returns for progressively more exercise.

The theory that over-doing exercise may cause more harm than good has neither been confirmed nor disproven. A science journal article by Masaru Teramoto reviewed fourteen studies of longevity of elite athletes. Athletes from endurance sports had 3-6 year longer life spans than the general population, but the results were mixed for athletes in power sports. The latter may be disadvantaged by larger body size typical of their sport or from a discontinuation of exercise as they age. The authors caution that elite athletes may by genetically different from the population as a whole, with both their abilities and lifespan being consequences of their genes rather than one causing the other.

There is a non-fatal problem with exercise – it is potentially addictive. As one well-known fitness expert author put it, “…people reduce their lives to fitness routines, training as many as 40 hours a week. That the effort may wreck marriages and compromise immune systems isn’t even relevant. To these people – demographically a diverse lot – exercise is addictive. The more the body gets, the more it wants. In return, the drug of exercise infuses the swimmer, cyclist and runner with two powerful illusions: that he/she is escaping the horrible, and progressing toward the divine.”


Beyond the story: Exercise-related articles on this blog include "Avoiding Overhydration" (Feb 2010), "Hypothermia" (Nov 2010) and "Recovery from Donating Blood" (March 2011). For a detailed, referenced take on death from exercise, go to the entry "Sudden Death and Exercise", in the Encyclopedia of Sports Medicine and Science:  http://www.sportsci.org/encyc/suddendeath/suddendeath.html.