Posted on April 11, 2017


Finally: An Explanation of Autism


I have reprinted an opinion piece from The New York Times. It traces a significant part of the autism epidemic to inflammation of the immune system. The same system that fights infection attacks the developing brain of the child before birth, though the damage is only obvious as the child develops.


August 25, 2012

An Immune Disorder at the Root of Autism


In recent years, scientists have made extraordinary advances in understanding the causes of autism, now estimated to afflict 1 in 88 children. But remarkably little of this understanding has percolated into popular awareness, which often remains fixated on vaccines.

So here’s the short of it: At least a subset of autism — perhaps one-third, and very likely more — looks like a type of inflammatory disease. And it begins in the womb.

It starts with what scientists call immune dysregulation. Ideally, your immune system should operate like an enlightened action hero, meting out inflammation precisely, accurately and with deadly force when necessary, but then quickly returning to a Zen-like calm. Doing so requires an optimal balance of pro- and anti-inflammatory muscle.

In autistic individuals, the immune system fails at this balancing act. Inflammatory signals dominate. Anti-inflammatory ones are inadequate. A state of chronic activation prevails. And the more skewed toward inflammation, the more acute the autistic symptoms.

Nowhere are the consequences of this dysregulation more evident than in the autistic brain. Spidery cells that help maintain neurons — called astroglia and microglia — are enlarged from chronic activation. Pro-inflammatory signaling molecules abound. Genes involved in inflammation are switched on.

These findings are important for many reasons, but perhaps the most noteworthy is that they provide evidence of an abnormal, continuing biological process. That means that there is finally a therapeutic target for a disorder defined by behavioral criteria like social impairments, difficulty communicating and repetitive behaviors.

But how to address it, and where to begin? That question has led scientists to the womb. A population-wide study from Denmark spanning two decades of births indicates that infection during pregnancy increases the risk of autism in the child. Hospitalization for a viral infection, like the flu, during the first trimester of pregnancy triples the odds. Bacterial infection, including of the urinary tract, during the second trimester increases chances by 40 percent.

The lesson here isn’t necessarily that viruses and bacteria directly damage the fetus. Rather, the mother’s attempt to repel invaders — her inflammatory response — seems at fault. Research by Paul Patterson, an expert in neuroimmunity at Caltech, demonstrates this important principle. Inflaming pregnant mice artificially — without a living infective agent — prompts behavioral problems in the young. In this model, autism results from collateral damage. It’s an unintended consequence of self-defense during pregnancy.

Yet to blame infections for the autism epidemic is folly. First, in the broadest sense, the epidemiology doesn’t jibe. Leo Kanner first described infantile autism in 1943. Diagnoses have increased tenfold, although a careful assessment suggests that the true increase in incidences is less than half that. But in that same period, viral and bacterial infections have generally declined. By many measures, we’re more infection-free than ever before in human history.

Better clues to the causes of the autism phenomenon come from parallel “epidemics.” The prevalence of inflammatory diseases in general has increased significantly in the past 60 years. As a group, they include asthma, now estimated to affect 1 in 10 children — at least double the prevalence of 1980 — and autoimmune disorders, which afflict 1 in 20.

Both are linked to autism, especially in the mother. One large Danish study, which included nearly 700,000 births over a decade, found that a mother’s rheumatoid arthritis, a degenerative disease of the joints, elevated a child’s risk of autism by 80 percent. Her celiac disease, an inflammatory disease prompted by proteins in wheat and other grains, increased it 350 percent. Genetic studies tell a similar tale. Gene variants associated with autoimmune disease — genes of the immune system — also increase the risk of autism, especially when they occur in the mother.

In some cases, scientists even see a misguided immune response in action. Mothers of autistic children often have unique antibodies that bind to fetal brain proteins. A few years back, scientists at the MIND Institute, a research center for neurodevelopmental disorders at the University of California, Davis, injected these antibodies into pregnant macaques. (Control animals got antibodies from mothers of typical children.) Animals whose mothers received “autistic” antibodies displayed repetitive behavior. They had trouble socializing with others in the troop. In this model, autism results from an attack on the developing fetus.

But there are still other paths to the disorder. A mother’s diagnosis of asthma or allergies during the second trimester of pregnancy increases her child’s risk of autism.

So does metabolic syndrome, a disorder associated with insulin resistance, obesity and, crucially, low-grade inflammation. The theme here is maternal immune dysregulation. Earlier this year, scientists presented direct evidence of this prenatal imbalance. Amniotic fluid collected from Danish newborns who later developed autism looked mildly inflamed.

Debate swirls around the reality of the autism phenomenon, and rightly so. Diagnostic criteria have changed repeatedly, and awareness has increased. How much — if any — of the “autism epidemic” is real, how much artifact?

YET when you consider that, as a whole, diseases of immune dysregulation have increased in the past 60 years — and that these disorders are linked to autism — the question seems a little moot. The better question is: Why are we so prone to inflammatory disorders? What has happened to the modern immune system?

There’s a good evolutionary answer to that query, it turns out. Scientists have repeatedly observed that people living in environments that resemble our evolutionary past, full of microbes and parasites, don’t suffer from inflammatory diseases as frequently as we do.

Generally speaking, autism also follows this pattern. It seems to be less prevalent in the developing world. Usually, epidemiologists fault lack of diagnosis for the apparent absence. A dearth of expertise in the disorder, the argument goes, gives a false impression of scarcity. Yet at least one Western doctor who specializes in autism has explicitly noted that, in a Cambodian population rife with parasites and acute infections, autism was nearly nonexistent.

For autoimmune and allergic diseases linked to autism, meanwhile, the evidence is compelling. In environments that resemble the world of yore, the immune system is much less prone to diseases of dysregulation.

Generally, the scientists working on autism and inflammation aren’t aware of this — or if they are, they don’t let on. But Kevin Becker, a geneticist at the National Institutes of Health, has pointed out that asthma and autism follow similar epidemiological patterns. They’re both more common in urban areas than rural; firstborns seem to be at greater risk; they disproportionately afflict young boys.

In the context of allergic disease, the hygiene hypothesis — that we suffer from microbial deprivation — has long been invoked to explain these patterns. Dr. Becker argues that it should apply to autism as well. (Why the male bias? Male fetuses, it turns out, are more sensitive to Mom’s inflammation than females.)

More recently, William Parker at Duke University has chimed in. He’s not, by training, an autism expert. But his work focuses on the immune system and its role in biology and disease, so he’s particularly qualified to point out the following: the immune system we consider normal is actually an evolutionary aberration.

Some years back, he began comparing wild sewer rats with clean lab rats. They were, in his words, “completely different organisms.” Wild rats tightly controlled inflammation. Not so the lab rats. Why? The wild rodents were rife with parasites. Parasites are famous for limiting inflammation.

Humans also evolved with plenty of parasites. Dr. Parker and many others think that we’re biologically dependent on the immune suppression provided by these hangers-on and that their removal has left us prone to inflammation. “We were willing to put up with hay fever, even some autoimmune disease,” he told me recently. “But autism? That’s it! You’ve got to stop this insanity.”

What does stopping the insanity entail? Fix the maternal dysregulation, and you’ve most likely prevented autism. That’s the lesson from rodent experiments. In one, Swiss scientists created a lineage of mice with a genetically reinforced anti-inflammatory signal. Then the scientists inflamed the pregnant mice. The babies emerged fine — no behavioral problems. The take-away: Control inflammation during pregnancy, and it won’t interfere with fetal brain development.

For people, a drug that’s safe for use during pregnancy may help. A probiotic, many of which have anti-inflammatory properties, may also be of benefit. Not coincidentally, asthma researchers are arriving at similar conclusions; prevention of the lung disease will begin with the pregnant woman. Dr. Parker has more radical ideas: pre-emptive restoration of “domesticated” parasites in everybody — worms developed solely for the purpose of correcting the wayward, postmodern immune system.

Practically speaking, this seems beyond improbable. And yet, a trial is under way at the Montefiore Medical Center and the Albert Einstein College of Medicine testing a medicalized parasite called Trichuris suis in autistic adults.

First used medically to treat inflammatory bowel disease, the whipworm, which is native to pigs, has anecdotally shown benefit in autistic children.

And really, if you spend enough time wading through the science, Dr. Parker’s idea — an ecosystem restoration project, essentially — not only fails to seem outrageous, but also seems inevitable.

Since time immemorial, a very specific community of organisms — microbes, parasites, some viruses — has aggregated to form the human superorganism. Mounds of evidence suggest that our immune system anticipates these inputs and that, when they go missing, the organism comes unhinged.

Future doctors will need to correct the postmodern tendency toward immune dysregulation. Evolution has provided us with a road map: the original accretion pattern of the superorganism. Preventive medicine will need, by strange necessity, to emulate the patterns from deep in our past.

Moises Velasquez-Manoff is the author of “An Epidemic of Absence: A New Way of Understanding Allergies and Autoimmune Diseases.”


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Oatmeal – Nutritious and Delicious

Posted on January 25, 2017

Oatmeal for Winter 2016 – 2017 Annual Update


Dr. Nadelberg and I frequently speak of mixing and matching foods to make balanced dishes. Consuming hearty foods is superior to counting calories or trying to stay on restrictive diets. Hearty foods diminish hunger; diets increase hunger. Below is an example of a good winter breakfast that balances carbohydrates and proteins, has beneficial fiber, and can be modified from day to day to keep your taste buds amused.



  1. You want rolled oats, otherwise known as old-fashioned oats. They have been flattened, steamed, and toasted, and take about five minutes to cook. If you have some skill with seasonings, you are all set. However, if shuffling around the kitchen in the dark of morning, you are just as likely to grab for the cayenne (yuck) as the cinnamon, try this: instant oatmeal comes in highly seasoned packets. While they are more processed than rolled oats, they are still good for you.
  2. The rolled oatmeal (takes 5 minutes to cook) is higher in fiber, helps digestion, and lowers cholesterol. The instant oatmeal (2 minutes to cook) has similar, but less pronounced, benefits, but comes in flavors such as Maple, Cinnamon, and Apple. Mix the two together and cook for five minutes.
  3. Instant oatmeal pre-measured packets are convenient for those normally skipping breakfast at home. Skipping breakfast is bad for your health. All you need is a microwave at the office. The other condiments (nuts, fruits) mentioned below are also portable, allowing one to have that all-important weight and metabolism controlling breakfast.

Balancing Nutrients:

  1. Adding a handful of nuts will bring this dish close to a balanced serving.  A serving of uncut oatmeal contains about 70% carbohydrate/30% protein/fiber. Instant oatmeal is 80% carbohydrate/20% protein/fiber.  Add 1/4 cup of cashews, pecans, or walnuts. They are softer than almonds and contain better fats than peanuts.
  2. You can sweeten this delicious breakfast with dried fruit, brown sugar, regular sugar, honey, berries, bananas, or fruit preserves while still maintaining a low glycemic nutritious breakfast.
  3. You can also add milled flaxseed to increase fiber and make it more filing.
This simple oatmeal breakfast lowers cholesterol and heart disease risk, improves digestion, and you can vary the flavors all winter long to suit your tastes.

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Light Pollution

Posted on December 28, 2016

Sometimes that Light at the End of the Tunnel is a Train

The Effect of Light at Night on Health

We just experienced the longest night of the year (Winter Solstice). We shorten the night with electric light. It is the largest uncontrolled experiment in human history. Two thirds of humanity cannot see the Milky Way galaxy at night because of light pollution. Cambridge, of all cities, recently proposed to increase light pollution. I gave testimony to the Cambridge City Council objecting to their proposed lighting ordinance. Below is a summary.


History on the light ordinance: On Jan. 11, 2015, the Zinc apartment complex turned on their rooftop, multicolored, high-intensity, LED lights. Visible from more than ten miles away, the neighborhood erupted in complaints about the “Las Vegas” display. The lights went off.


The City drafted a new regulation which would allow placements of high intensity displays in about 1/3 of the city in exchange for permitting fees, with the proviso they be turned off from midnight to 6 AM, effectively, in this doctor’s opinion, creating an epidemic of insomnia and sleep related health issues.


What happens when we disrupt sleep? There are more car accidents, work-related injuries, heart attacks, cluster headaches, diabetes, obesity, depression, gastrointestinal problems, decreased fertility, and in two recent reports, breast cancer. Children do worse in school. People’s pre-existing sleep disorders get worse. Sound attractive? Think permitting fees can pay for this sort of damage?


To be fair, it isn’t just outdoor lighting that’s the problem. All your flat screens – flat screen televisions, iPads, and smart phones – project high intensity blue light, creating indoor light pollution. Both fall under a new medical syndrome – Artificial Light at Night (ALAN).


Lighting Facts

There are four issues in lighting; exposure, duration, intensity, and color. I will use the Cambridge situation as illustration.


Exposure: The City incorrectly assumes the intensity of light measured directly across from the source is accurate. Light may travel in a straight line in outer space, but down here on earth it, reflects off clouds, snow, fog, air pollution, walls and windows, and cars and trucks – even puddles. The environment in certain parts of the city act like a reflector – the intensity of reflected light will be greater than line-of-sight measurement.


Duration: Adults need 7 to 9 hours of sleep a night, teenagers need 12 to 14, and newborns much more. Disturb this circadian rhythm by having lights on too long and illness results. The Cambridge light ordinance legislates six hours of lower light (12AM-6AM). It takes your brain an hour to recover from bright light before it starts secreting sleep inducing melatonin. So, they legislated five hours of sleep. Less than 2% of adults function well at this level, worse for children.


Intensity: The advent of Light Emitting Diodes – LED’s – has created an epidemic of overly bright lighting. The incandescent bulb turns 100 W electricity into 100 W of light. With an LED, it only takes 7 to 15 W to produce 100 W. The City put high intensity LEDs in West Cambridge, believing they could save money. One can stand on the front steps of those houses and read a book at 3 AM. Lights should be placed to create safe streets, not lighted doorsteps. In some houses, one can read a book indoors from the outside light. The lights should be replaced, but could be modified with shades or dimmers.


Color: The color of light determines how much it scatters. Pure red light scatters very little; it penetrates skin deep enough to show blood vessels. Blue light, however, reflects off surfaces. Blue lights are used by law enforcement because they can be seen at the greatest distance. The high-intensity blue light in West Cambridge can work its way around corners, including light darkening window shades. As anyone with cataracts knows, the high-intensity blue LEDs used on many automobiles create scatter inside the eye.


Light is measured in Kelvin, blue is 4000K+; much softer and less reflective yellow is 2700K. If one chooses more efficient blue lights, they can be placed on dimmer switches. Even better, if one uses a more yellow tone light, such as in Harvard Square, and places them on dimmers and timers, the result has been remarkably few complaints in that neighborhood. This is not rocket science.


The city already has a history of putting in both health sensitive and health insensitive lighting projects. The high intensity, unshaded, 5000 Kelvin blue streetlights in West Cambridge, installed in 2012, are a source of continuing complaints. In contrast, the lights in Harvard Square, though slightly less energy-efficient, are occupant and tourist friendly.  And, yes, if one adds in the health problems prevented, a bargain. I remember hearing something about an ounce of prevention.


Take Away Lesson

Pay careful attention to those boring announcements about town planning projects. If you are planning on replacing lights in your house with LED’s, you should get a few lights between 2700 and 3000 K, and find which ones are most pleasing to you. I strongly recommend you use lights on dimmer switches; you may have to replace your old light switch with LED compatible ones. You should avoid using laptops, IPad, smartphones, and flat screen TV’s the hour before bedtime. Unless, of course, you have an application to change the frequency of light on the display.



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Consumer Reports on Supplements: The Good, the Bad, and the Ambiguous

Posted on August 16, 2016

The Good


In its September 2016 magazine, Consumer Reports has an extensive review of dietary supplements. They present a very good history of the supplement industry, which got its impetus from Linus Pauling, two-time Nobel Prize winner, and his claims in the 1980’s that 3000 mg of vitamin C would abolish the common cold. With over 25,000 articles published on the subject since, it’s safe to say this theory is disproved. He did, however, endow the University of Oregon to found the Linus Pauling Institute for the study of micro nutrients, which does quite good work, and I recommend you visit the site.


Consumer Reports also presents a history of the Dietary Supplement Health and Education Act (DSHEA) of 1994, which was lobbied through Congress by the supplement manufacturers, and exempted them from the FDA drug approval process. It created regulations for manufacturing inspection that are largely unfunded to this day, and created rules that prohibited companies from claiming that a supplement can cure or treat a specific disease. However, manufacturers have crossed that line numerous times because the act does not provide sufficient monitoring. Consumer Reports did not mention that supplement claims are still subject to Federal Trade Commission investigation for false claims in advertising. FTC fines average 3 million dollars; some companies consider that a cost of doing business.


The Bad


Consumer Reports published a list of 15 supplements to avoid. Since 1994, the number of supplements on the market has expanded from 4,000 to 90,000.  So there are hundreds of supplements to avoid, including many that are useless, mislabeled, contaminated, or adulterated with pharmaceuticals. It’s not unusual, when patients come to the office and we review the supplements they are taking, that we recommend them to stop taking about half (and start some different ones). The current system does not provide adequate inspection, and there is no voluntary compliance system in place either. Maintaining purity in the manufacture of food or drugs is difficult, and even the largest manufacturers, such as Tyson Foods or Merck pharmaceuticals, are subject to recalls and fines. Considering how low the bar is for entry into supplement business, it’s not surprising that the Atty. Gen. of New York found that four out of five herbal supplements at GNC and Walmart did not contain the substances mentioned on the label. As Consumer Reports correctly notes, strengthening regulations is “just one crisis away.”


Consumer Reports also did not issue a caution on what I call “supplement alchemy.” Multivitamins, contain many vitamins and minerals, without which people will experience deficiency diseases such as pellagra, scurvy, beri beri, rickets, etc. Supplement manufacturers put together combinations of nutrients for which there are no known deficiency states or diseases. The label will say something like “supports immune function” for which there is about as much evidence that the air under the Zakim bridge “supports” the structure. Or one can go to the, which, while having a pronounced conservative bias, documents many of the overstatements and shenanigans that plague the supplement industry. They list over 70 supplements one might wish to know more about. Caveat emptor.


The Ambiguous


Consumer Reports fails to mention how gray the line can be between a supplement and a pharmaceutical. The same supplement can be a pharmaceutical, or, alternatively, supplements are drugs. In America, melatonin is a supplement; in Europe you need a prescription. In America, progesterone and codeine are available by prescription only; in Europe they’re over-the-counter. Omega-3 fish oil is available as a supplement and as a prescription (Lovaza and Amacor). Both are purified using similar procedures. There have been inconsistent results in clinical trials, as I noted in an earlier newsletter, because scientists have not measured the oxidation in the fish oils they were using. I would imagine that spoiled fish oil doesn’t work very well. A recent trial of Lovaza showed it was quite beneficial after a heart attack. Lovaza is probably less oxidized than supplements because the pharmaceutical pipeline is much more efficient. And at 10 times the cost of a supplement, it is probably handled better.


This ambiguity applies to herbals as well. The leaf of the French Lilac will lower blood sugar; it contains a molecule called metformin. Metformin, a prescription, is considered to be the first line drug to treat diabetes (along with diet and exercise.) If we used every inch of arable forest to produce French lilacs, we could not produce 1% of the metformin consumed across the world.


Consumer Reports compared red yeast rice unfavorably to statin medications for the treatment of elevated cholesterol. The reality is that red yeast rice contains the same molecule as in the statin drug lovastatin, and this is a principal way that it works. Penicillin comes from a mold. There is some evidence the ancient Egyptians may have used it as a medicine. Statin drugs come from a fungus. It’s just not that simple


Like many things in medicine, our understanding of medical benefits and risks change over time. Approximately one third of pharmaceuticals are prescribed for uses not originally approved by the FDA. Because of the cost of going back for additional FDA approvals is so high, this is simply called an “off label” use. Physicians are constantly adapting to this shifting landscape; most now advise patients about supplements as well. 7% sell supplements from their offices.


Consumer Reports mentions that patients taking acid blocking drugs such as Prevacid or Nexium might need supplementation with magnesium and B-12. Acid blocking drugs, commonly given for reflux, actually decrease the absorption of B12, magnesium, iron, calcium, fully casted, and zinc. To achieve better absorption of calcium, patients frequently have to take increased vitamin D and vitamin K2. In addition, the acid blockers can contribute to an increased risk of infection including pneumonia, Clostridium difficile, and cognitive impairment. Lastly, in a study from the Mayo Clinic, the majority of young women on acid blocking drugs actually suffered from delayed gastric emptying and didn’t need acid blocking drugs in the first place. These are complicated questions and you should consult your physician.



There is a large and growing body of scientific evidence concerning utility of supplements. Consumer Reports mentions a few, such as folic acid in pregnancy, or vitamin D in osteoporosis. They rightly point out that neither supplement labels and of the salespeople give adequate warnings about adverse effects and interactions. But they failed to tackle the difficult issues, such as the supplement industry insisting patients need more vitamin D years before the medical community recognized the need. In considering taking a supplement, you must balance “common wisdom” such as Linus Pauling statements about vitamin C, against the fact that the amount of funds available for research don’t go to supplements, because they are not as profitable as pharmaceuticals.


However, part of the promise of supplements has been proven true in multiple scientific studies. They tend to have fewer adverse effects than pharmaceuticals used for similar conditions. For men developing prostatic hypertrophy, saw palmetto or beta-sitosterol can produce significant symptomatic relief with far fewer side effects than finasteride, which can produce temporary impotence, or Tamsulosin, which can produce fainting spells. On the other hand, in an effort to avoid side effects, many people delay the care they need. No one may look further than Steve Jobs, who used alternative care for his neuroendocrine pancreatic cancer, and probably reduced his survival by several years.


Genetics is also showing that supplements have unique benefits for certain individuals. Those with multiple mutations to the MHTFR gene will absorb methyl folate better that standard folic acid (and for those without mutations – the majority of people – the more expensive methyl folate is a waste of money.)  Statins, like Lipitor, can cause muscle aches, which is the most frequent reason people stop taking the class of drugs. Vitamin D deficiency increases the incidence of this myalgia, and correction of the deficiency will frequently abolish the side effect.  Statin drugs reduce CoEnzymeQ10, in some cases in as little as two weeks. Results with CoEnzymeQ10 show similar benefit; the studies are inconsistent because some forms of CoEnzymeQ10 are poorly absorbed. The genetics around statin metabolism, centered around gene SLCO1B1 are still being worked out. However, compliance with prescribed medication in the US is barely 60%; compliance with returning to a medication that has caused a toxic reaction is about 5%. So, among other reasons, Dr. Nadelberg and I treat our patients on statins with Vitamin D and CoEnzymeQ10 to maximize compliance with these important medications.


Age Management Boston

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“Truth” About Supplements?

Posted on January 25, 2016

WGBH Frontline Slams Supplements


There are many ongoing controversies about the use of supplements and their effects on people’s health. The supplement industry in the United States could best be described as a bazaar with various companies hawking their goods based on either carefully worded statements, such as “supports immune function” or testimonials by individuals. What is noticeable is that a $36 billion a year industry does not fund research on its own products.  The industry is protected by a bill that exempts it from regulation by the FDA.


There are many supplements with overstated claims, supplements mislabeled as to the contents, and some are just plain bad for you.


However, there is also medical evidence that supplements, taken in the proper amounts, and with proper manufacturing, are beneficial to health. The bark of the willow tree was the origin of aspirin, the leaf of the French Lilac was the origin of Metformin, and penicillin comes from a species of mold. And the poison strychnine comes from a seed. There is no guarantee of benefit or harm.


The WGBH broadcast criticized the consumption of both multivitamins and megadose vitamins. Megadose vitamins, especially fat-soluble ones like vitamin E, are clearly bad for health. However, a daily multivitamin is recommended by the Linus Pauling Institute at the University of Oregon to compensate for the depleted nutrition in the American food supply and in the average American diet.


Herbal products, like St. John’s wort or ginkgo biloba are rarely pure, frequently have fillers, and their labels do not reflect the contents. The broadcast was correct that DNA testing demonstrated that the vast majority of herbals are a crapshoot as to contents. More enlightened manufacturers are turning to DNA barcode testing to improve their products.


The section on omega-3 fish oils was outright misleading. There are studies in which fish oil is amazingly effective for changing lipid profiles and reducing cardiac death. However, equal numbers of studies show no effect. In 2014, a review article pointed out that almost no researchers tested fish oil products for oxidation; the author suspected that oxidized fish oil produces negative results, while fresh fish oil is beneficial. As an amusing aside, the pharmacist who pointed out the problems with fish oil did not mention that, in his most recent conflict of interest filing, he receives support from seven pharmaceutical firms. The point that fish oil from fish may be more effective than fish oil capsules does have some scientific merit; however fish oil capsules have less mercury in them than the fish they came from.


The section on vitamin D is critical of anyone taking more than 2000 units a day. It did not mention the relationship between dosage recommendations and vitamin D deficiency. The idea, unstated in the broadcast, is that if one has adequate levels of vitamin D, 2000 units a day is more than adequate. However, in conditions of vitamin D deficiency, the American Journal of clinical nutrition recommends dosages up to 20,000 units a day. The definition of vitamin D deficiency 30 years ago was a level of 14; today it is a level of 32. Similarly, the level of toxicity 30 years ago was 50; today it is 100. The changing target levels are grudging acknowledgment by the medical establishment that vitamin D is beneficial.


In point of fact, at Age Management Boston, we subscribe to databases and testing agencies in order to evaluate all supplements we recommend. Like many things in medicine, there are open questions, and I encourage people to keep an open mind. In this case however, I thought Frontline missed the educational opportunities that educational television strives for.

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The Institute of Medicine on Vitamin D

Posted on January 14, 2016

Safe Supplementation of Vitamin D

This study, which recommends people to consume three times more vitamin D than the Institute recommended in 1997, also concludes that consuming more vitamin D could be hazardous. The flaw in the report is its structure which flows through to its conclusions.  The Institute only considered large randomized controlled trials or large cohort trials.  Observational trials and case control trials, which represent the large majority of studies, were excluded.  The Institute also failed to exclude randomized trials that were flawed. In addition, even when a small component of a large trial demonstrated a positive effect from vitamin D, the report only discussed the whole trial as if the focused study did not exist.  Much of the commentary concentrated on vitamin D deficiency causing disease, rather than vitamin D sufficiency preventing disease.

Nonetheless, they could not exclude information from major studies that demonstrate the effectiveness of vitamin D.  On page 122 (of 981 pages) of the report, the Institute cites the Framingham Offspring Study, which clearly demonstrated declining rates of cardiovascular disease as levels of vitamin D rose to 70 ng/mL. They also failed to include subsets of data from the largest survey of nutrition in the US, which has the acronym NHANES (The National Health and Nutrition Examination Survey), and is repeated periodically (NHANES I, NHANES II etc). NHANES I, published in 1988, was responsible for noting the relationship were patients with higher vitamin D consumption had lower rates of breast cancer. This result has been confirmed in other studies. The benefit of vitamin D above 70 ng/mL has not been demonstrated so I don’t recommend it; the last case of vitamin D toxicity reported to the US Poison Control Centers had a level well over 100 (actually 482!). In terms of harm, almost every study showing harm involved the simultaneous administration of calcium with vitamin D.  Excessive calcium administration is bad for you, even without vitamin D.

I reviewed my library of 46 original publications ranging from the American Journal of Clinical Nutrition to the New England Journal of Medicine.  I found well-done studies which indicate vitamin D’s association with reductions in cardiovascular disease, cancer, diabetes, and it certainly makes for stronger bones.

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Testosterone Aiding the Heart

Posted on January 11, 2016


Proper Doses of Testosterone Reduces Heart Attack Risk


A new Veteran’s Administration study looked at records of 83,000 men, average age 66, with no evidence of heart disease or stroke and low total testosterone (TT) at the beginning of the study. Only men with confirmed low TT were included in the study. They were divided into three groups – those that achieved normal TT with treatment, those who were treated but never achieved normal TT, and those who refused treatment.


During seven years of observation, those who achieved normal testosterone levels were 47% less likely to die, had 18% fewer heart attacks, and 30% fewer strokes. Those whose TT level never rose to the normal level had the same hazard as those who had no treatment – no benefit at all. (Treatment failures are caused by lack of absorption of skin creams or lack of compliance, frequently due to cost.)


These results are not surprising. Doctors have known for 50 years that low testosterone shortens life span, increases heart attacks, strokes, and osteoporosis. Secondly, without testosterone supporting muscle function, the same men have an increased risk of obesity, type 2 diabetes, and a host of related disorders.


Two earlier studies, also from the Veterans Administration, received the headlines. They concluded that testosterone administration increased the risk of heart attack in men. However, neither study consistently checked testosterone levels prior to, or during each study. Dr. Nadelberg and I had a letter published in the Journal of the American Medical Association challenging these methods.


So identifying testosterone deficient men and carefully monitoring testosterone supplementation can have significant benefits. Please understand that the definition of a hormonal deficiency is more complicated than a single number on a lab test, and that treatment, while beneficial, is not without risks.


And now, I will discuss the limitations of this study. First, all of the subjects or patients were of the Veterans Administration hospital system. Veterans, as a group, have more chronic illnesses than the general population. Showing that testosterone works well in this group does not mean it would work well with all patients (theoretically, it could also work better in the general population, but improving on a 40% reduction in mortality is unlikely). For example, Lipitor reduces cardiac events in post heart attack patients by almost 20%, but only reduces heart attacks in the general population by about 2%. The study did not consider symptoms of hypogonadism. The study did not look at lifestyle, such as exercise.  Lastly, the study tweaked its statistics by about 4% by using a manipulation called propensity scoring. The definition of “normal” testosterone level is a subject of intense scientific debate. The study did not supply any guidance, such as the percent improvement in testosterone level, so that clinicians could judge where the author stood in the debate on normal


However, you did not see a headline that read “Testosterone Replacement Therapy (TRT) is More Effective than Lipitor for Preventing Heart Attack!” One retrospective study, no matter how large, or well conducted, would be proof of such an assertion. On the other hand, we have seen recent headlines about testosterone treatment causing heart attacks, and the FDA announcing an investigation.


Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men. Rishi Sharma1, Olurinde A. Oni1, Kamal Gupta2, Guoqing Chen3, Mukut Sharma1, Buddhadeb Dawn2, Ram Sharma1, Deepak Parashara2,4, Virginia J. Savin5, John A. Ambrose6, and Rajat S. Barua1,2,4*

Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA 2013;310:1829–1836, Finkle WD, Greenland S, Ridgeway GK, Adams JL, Frasco MA, Cook MB, Fraumeni JF Jr, Hoover RN.

Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS ONE 2014;9:e85805. 13. Baillargeon J, Urban RJ, Kuo YF, Ottenbacher KJ, Raji MA, Du F, Lin YL, Goodwin

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Just the Flax and Nothing but the Flax

Posted on October 2, 2015

The benefits of flaxseed have been described for decades. Flaxseed has a very hard husk and contains several oils. If you eat flaxseeds whole, they will pass through undigested. In practice, the seed is crushed and the oil is harvested. Fish oil is a better source of DHA and EPA, and unless you are allergic to fish, they are the better source. The most important component of the flaxseed is the husk. It is rich in lignin, which has the unique property of binding toxic substances, such as LDL cholesterol and lipoprotein-a, reducing atherosclerotic heart disease, and through a different mechanism, reducing prostate and breast cancer. Many patients with years of irritable bowel syndrome have found relief with milled flax.


The way to maximize lignan exposure is to mill the flaxseed. How one mills can make a significant difference. Historically, the milled seeds contained about 10% to 15% oil, were purchased fresh, and then sold refrigerated or freeze-dried, and kept refrigerated until consumed. Left on the counter, exposed to sun and air, milled flaxseed becomes rancid in 2 to 3 weeks.


I recently found milled flaxseed that doesn’t require refrigeration. It has 5 to 7% oil content and neither smells or tastes like it’s forebear. Researching the topic, I discovered there are four ways to commercially mill flaxseed.  More intense milling results in higher temperatures, smaller particles, and more oil extraction. No one has published an article comparing how this processing affects the binding capacity of hot-milled flax, but I think agricultural science has again found a way to produce a less nutritious product from a better one.


Until I see evidence that this new flaxseed is superior to the old, I would advise sticking with the old.  Colder milled flax is proven to reduce cholesterol, LDL cholesterol, lipoprotein a, and block receptors that are implicated in prostate and breast cancer.  It is the only substance known to bind lipoprotein-a, which the American Heart Association has declared to be a significant independent risk for heart disease. Since I found the suspect flaxseed at Whole Foods, I can only advise you to read labels carefully.  Otherwise, Swanson Vitamins has an inexpensive freeze-dried milled flaxseed.

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Welcome to the New American Heart Attack

Posted on September 29, 2015

The “Hollywood Heart Attack” – sudden, intense, left shoulder and arm pain, crushing chest pain, nausea, sweating and collapse – is ingrained into the American psyche. It is the most memorable presentation, but the majority of heart attacks, in both men and women, don’t present that way.

Martha Lear, wife of famed producer Norman Lear, wrote about her heart attack in the New York Times in 2014 –
“altogether well one moment, vaguely unwell the next; fluttery sensation at the sternum, rising into the throat; mild chest pressure; then chills, sudden nausea, vomiting, some diarrhea. No high drama, just a mixed bag of somethings that added up to nothing you could name. Maybe flu, maybe a bad mussel, maybe too much wine, but the chest pressure caused me to say to my second husband, “Could this be a heart attack?” “Of course not,” he said. “It’s a stomach bug.”

Still, that pressure, slight but there, nagged at me. I called my doctor and reported my symptoms. The mention of diarrhea, almost never a presenting symptom in heart attacks, skewed the picture. He said, “It doesn’t sound like your heart. I can’t say a thousand percent that it’s not, but it doesn’t seem necessary to go racing to the emergency room with the way you feel now. Just see it through and come in for an EKG in the morning.”

The pressure eased. I slept, and woke the next morning feeling well. I went for the test mainly because I had said that I would, fully expecting to be told that I was healthy. First the EKG and then the echocardiogram told a different story: a substantial heart attack, “less than massive,” my doctor said, “but more than mild.” 
She was admitted to the hospital, had her blocked artery opened with a stent, and continues to write about health matters.

But it is not just women.

A 65-year-old businessman is sitting in his office in Copley Square when he suddenly gets a feeling of being totally “washed out.” He has a slight feeling of heartburn, but not sufficient to reach for an antacid. He exercised regularly, ate sensibly, had a reasonable cholesterol. One side of his brain said “this can’t be happening to me.” The feeling of profound fatigue persisted and the other side of his brain jumped in – he recalled the ads on TV, took several aspirin, and drove to a nearby hospital. He parked his car and walked into the ER. Within minutes of setting foot in the Emergency Department, his heart attack was diagnosed and being treated. He did fine after bypass surgery.

A review of roughly 1 million heart attacks by Canto (published in the Journal of the AMA in 2012) showed that roughly 20% of male heart attacks, and 50% of female heart attacks do not resemble the Hollywood Heart Attack. Primary symptoms were weakness, cold sweats, and trouble breathing. And frequently a pattern of sleep disturbances and unexplained fatigue in the days prior. The average heart attack survivor delays going to the ER for two hours.

Don’t wait for the Hollywood Heart Attack! New persistent ill feelings are all you need to experience one of life’s greatest opportunities – interventional cardiology – it really saves lives. But you have to show up!

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Death by Breakfast

Posted on August 8, 2015

After the enthusiastic response to my oatmeal recipe, I thought I should counter with a breakfast warning. Most of you have been deafened with recommendations to “eat fruits and vegetables,” however not all fruits and vegetables are equal. Here is a synopsis of a cautionary tale from The New York Times.

A 42-year-old was barely responding when her husband brought her to the emergency room. Her heart rate was slowing, and her blood pressure was falling. Doctors had to insert a breathing tube, and then a pacemaker to revive her.

The patient’s husband said she suffered from migraines and was taking a blood pressure drug called verapamil to help prevent the headaches. But blood tests showed she had an alarming amount of the drug in her system, five times the safe level.

Did she overdose? Was she trying to commit suicide? It was only after she recovered that doctors were able to piece the story together.

She had a migraine and could not tolerate anything else but grapefruit.

The previous week, she had been subsisting mainly on grapefruit juice. Then she took verapamil, one of dozens of drugs whose potency is dramatically increased if taken with grapefruit. In her case, the interaction was life-threatening.

Last month, Dr. David Bailey, a Canadian researcher who first described this interaction more than two decades ago, released an updated list of medications affected by grapefruit. There are now 85 such drugs on the market, he noted, including common cholesterol-lowering drugs, new anticancer agents, and some synthetic opiates and psychiatric drugs, as well as certain immunosuppressant medications taken by organ transplant patients, some AIDS medications, and some birth control pills and estrogen treatments. (The full list is online; your browser must be configured to handle PDF files.)

“What drove us to write this paper was the number of new drugs that have come out in the last four years,” said Dr. Bailey, a clinical pharmacologist at the Lawson Health Research Institute, who first discovered the interaction by accident in the 1990s.

How often such reactions occur, however, and how often they are triggered in people consuming regular amounts of juice is debated by scientists. Dr. Bailey believes many cases are missed because doctors don’t think to ask if patients are consuming grapefruit or grapefruit juice.

Even if such incidents are rare, Dr. Bailey argued, they are predictable and entirely avoidable. Many hospitals no longer serve juice, and some prescriptions carry stickers warning patients to avoid grapefruit.

“The bottom line is that even if the frequency is low, the consequences can be dire,” he said. “Why do we have to have a body count before we make changes?”

For 43 of the 85 drugs now on the list, consumption with grapefruit can be life-threatening, Dr. Bailey said. Many are linked to an increase in heart rhythm, known as torsade de pointes, that can lead to death. It can occur even without underlying heart disease and has been seen in patients taking certain anticancer agents, erythromycin and other anti-infective drugs, some cardiovascular drugs like quinidine, the antipsychotics lurasidone and ziprasidone, gastrointestinal agents cisapride and domperidone, and solifenacin, used to treat overactive bladders.

Taken with grapefruit, other drugs like fentanyl, oxycodone and methadone can cause fatal respiratory depression. The interaction also can be caused by other citrus fruits, including Seville oranges, limes and pomelos; one published case report has suggested that pomegranate may increase the potency of certain drugs.

Older people may be more vulnerable, because they are more likely to be both taking medications and drinking more grapefruit juice. The body’s ability to cope with drugs also weakens with age, experts say.

Under normal circumstances, the drugs are metabolized in the gastrointestinal tract, and relatively little is absorbed, because an enzyme in the gut called CYP3A4 deactivates them. But grapefruit contains natural chemicals called furanocoumarins, that inhibit the enzyme, and without it the gut absorbs much more of a drug and blood levels rise dramatically.

For example, someone taking simvastatin (brand name Zocor) who also drinks a small 200-milliliter, or 6.7 ounces, glass of grapefruit juice once a day for three days could see blood levels of the drug triple, increasing the risk for rhabdomyolysis, a breakdown of muscle that can cause kidney damage.

Estradiol and ethinyl estradiol, forms of estrogen used in oral contraceptives and hormone replacement, also interact with grapefruit juice. In one case in the journal Lancet, a 42-year-old woman taking the birth control pill Yaz developed a very serious clot that threatened her leg several days after she started eating just one grapefruit a day, said Dr. Lucinda Grande, a physician in Lacey, Wash., and an author of the case report.

But Dr. Grande also noted that the patient had other risk factors and the circumstances were unusual. “The reason we published it as a case report was because it was so uncommon,” she said. “We need to be careful not to exaggerate this.”

Some drugs that have a narrow “therapeutic range” — where having a bit too much or too little can have serious consequences — require vigilance with regard to grapefruit, said Patrick McDonnell, clinical professor of pharmacy practice at Temple University. These include immunosuppressant agents like cyclosporine that are taken by transplant patients to prevent rejection of a donor organ, he said.

Still, Dr. McDonnell added, most patients suffering adverse reactions are consuming large amounts of grapefruit. “There’s a difference between an occasional section of grapefruit and someone drinking 16 ounces of grapefruit juice a day,” he said.

And, he cautioned, “Not all drugs in the same class respond the same way.” While some statins are affected by grapefruit, for instance, others are not.

Here is some advice from experts for grapefruit lovers:

¶ If you take oral medication of any kind, check the list to see if it interacts with grapefruit. Make sure you understand the potential side effects of an interaction; if they are life-threatening or could cause permanent injury, avoid grapefruit altogether. Some drugs, such as clopidogrel, may be less effective when taken with grapefruit.

¶ If you take one of the listed drugs on a regular basis, keep in mind that you may want to avoid grapefruit, as well as pomelo, lime and marmalade. Be on the lookout for symptoms that could be side effects of the drug. If you are on statins, this could be unusual muscle soreness.

¶It is not enough to avoid taking your medicine at the same time as grapefruit. You must avoid consuming grapefruit the whole period that you are on the medication.

¶In general, it is a good idea to avoid sudden dramatic changes in diet and extreme diets that rely on a narrow group of foods. If you can’t live without grapefruit, ask your doctor if there’s an alternative drug for you.

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