- I. Welcome to the Microbiome
Science is full of surprises. Right about the time we developed radio telescopes that can look back 15 billion years to the origin of the galaxy, we discovered that the galaxy we can see is only one third of the universe. Suddenly “dark matter” and “dark energy” surround us, or so it might appear. The reality is they have been there all along.
The sequencing of the human genome is a pinnacle of science. While we have identified the 30,000 human genes, we also discovered that “dark regions” make up the majority of our DNA. What we have learned about the 30,000 genes is that they act in combinations that are almost infinite. However, they interact with our environment to the degree that genetics predicts only about 30% of our future health. The genetic/environmental interaction determines the rest. Our understanding of life got more complex when we started sequencing various other species on the planet. A good, red garden tomato has three times the number of genes as Einstein.
So what is it in our environment that we interact with? Pesticides? Air pollution? Our food? In each instance, like gazing at stars, we have looked too far afield. We carry within and on our body several pounds of bacteria and fungi with which we interact constantly and intimately – so intimately that we have integrated some nonhuman DNA into our own! A human is roughly 10 billion cells; the microbiological load we carry – the microbiome – is 100 trillion cells. While human DNA is roughly 99% identical from one person to the next, each microbiome is only 50% similar. If we look at evolution, DNA is a cranky, stubborn little computer that reluctantly adapted to prolonged climate, agricultural, and/or predator changes. However, our microbiome can shift dramatically in weeks, and can transfer capabilities to other individuals as well as the next generation through simple contact. Think of DNA as internal, permanent evolution, and the microbiome as external, adaptive evolution, capable of changing multiple times within the life of the individual. Please read “Our Bugs, Ourselves” in the Harvard Health Magazine.
II. Is Carnitine in Meat a Principal Cause of Heart Disease? (No!)
Stanley Hazan, of the Cleveland Clinic, published a paper in Nature Medicine which showed that mice, when fed the supplemental protein l-carnitine, produced trimethylamine-N-oxide (TMAO), a known accelerator of atherosclerosis. Further, the paper shows that meat-eating humans produce more TMAO than do vegetarians. Lastly, when the intestinal bacteria of mice were suppressed with antibiotics, their TMAO production did not rise even though the mice were fed l-carnitine. The new theory is that carnitine, via TMAO, changes the metabolism of cholesterol, creating more deposits in artery walls.
Is it time for all meat eaters to throw their beef off the cliff?
Maybe not; part of Hazan’s study showed a correlation between high blood carnitine levels and heart disease. However, in studies of heart attack, congestive heart failure, and cardiomyopathy, distressed cardiac muscle leaks carnitine, resulting in low intracellular levels and high blood levels. When given more l-carnitine, the stressed myocardium improves. So it begs the question – just how long before an acute event does the leaking begin? Perhaps Dr. Hazan should have measured intracellular l-carnitine?
There is extensive research on l-carnitine going back to 1965, demonstrating that it decreases mortality in heart attacks and decreases arrhythmias. It has never been very good for muscle building, but it does help in reducing recovery time between exercise sessions, especially as one ages. Because it is a natural substance, it cannot be patented, and is not attractive to large pharmaceutical firms. The most recent study of l-carnitine, published in the Mayo Clinic proceedings this year, showed improvement in congestive heart failure. There are also children born with a genetic inability to produce l-carnitine. They lead normal lives with supplementation and have not shown any evidence of increased atherosclerosis after a lifetime of l-carnitine well above normal levels for their protection.
This is the typical nutritional mosaic – highly contrasting research findings. The missing piece in this Angel versus Devil piece of metabolism is an understanding of the microbiome. Carnitine is found in many foods besides red meat, including chicken, pork, milk, and fish. Is it meat consumption alone that creates TMAO-generating bacteria? Or do meat eaters have other evil habits that are responsible? In addition, choline, phoshotidyl-choline, and lecithin have also been linked to TMAO. These proteins are found in hundreds of foods. That would change carnitine from a cause to a marker. Lastly, bodybuilders consume enormous quantities of carnitine in protein shakes, yet have no documented increased risk of atherosclerosis. Are their microbiomes generating an antidote to TMAO that keeps it in balance?
My advice is to look at the world wide metabolic ecology and then let our intuition guide us so that we don’t miss the 500 pound gorilla in the middle of the room while distracted by something new and sexy. The theory that meat-containing carnitine creates TMAO which then activates cholesterol is best viewed in reverse. Numerous groups – Hunza tribesman, Masai herdsman, rural Chinese, all with radically different diets – have almost no heart disease. They all have total cholesterol far below the Hazan study group. We know from the Asteroid trial that when total cholesterol gets down towards 130, atherosclerosis reverses. In point of fact, this is the mammalian “sweet spot” for cholesterol and it applies to elephants, gorillas, and even dogs and cats, who have similar cholesterol levels and no heart disease. At Age Management Boston, we are guided by this data. The average American diet ruins insulin control, leads to metabolic syndrome, numerous inflammatory conditions, and disease. In this context, carnitine in meat is like rearranging the chairs on the Titanic. A healthy diet, adequate sleep, and exercise more than likely create a microbiome that can handle lean meats just fine. And considering the amount of time we have been exposed to meat, there may even be specific DNA adaptations for meat eaters – there are indications the Masai have achieved this.
III. Update on the FDA and Compounding Pharmacies
The prescribing of hormones has become more challenging as pharmacies in multiple states, having seen the FDA pressure pharmacy closures, have ceased observing many of the everyday courtesies in medical practice in favor of the “letter of the law.” Prescriptions that could be called in now must be faxed, or even the original mailed. There are three national ID numbers for each physician – and some pharmacists who have known mine for years now insist I use them all. Eventually, Congress will grant the FDA authority over all prescribing including compounding pharmacies. This standardization will work its way into electronic prescribing and this period of turmoil will pass. But anticipate headlines about FDA inspections, closures, and fines until then.