Nine basic principles of chemistry and biology that will help you better understand supplements
In prior emails, I reviewed the DSHEA laws establishing a dichotomy splitting medications into supplements vs drugs. This has led to a lot of confusion and a supplement double standard - supplements are perceived by patients as both effective and having no side effects. In this email, I intend to examine supplements and drugs on a molecular level to help explain why this is a misleading dichotomy. Supplements and drugs are one and the same. They are both concentrated chemicals that interact with complex biological systems.
Bridging the doctor-patient disconnect
There is somewhat of a disconnect between patients and science-based doctors. I believe this disconnect stems from a difference in basic science background. A doctor’s worldview is rooted in thousands of hours of chemistry, biochemistry, physiology, cellular biology, and pharmacology. These disciplines offer us a remarkably reliable and reproducible model of nature.
Without basic science knowledge, however, one is susceptible to pseudoscience. Confident speakers like Dr Oz, Dr Hyman, Dr Weil, and Dr Mercola offer simple explanations with dramatic testimonials - it’s hard to resist.
In an age where many patients are taking health into their own hands (which I applaud), it is imperative for them to learn and understand basic science principles. In the following, you will find nine basic principles that relate to the understanding of supplements and drugs. Once we bridge this basic science disconnect, the real conversation begins.
Principle #1 - Chemicals are the active ingredients in nature
Why does Coffee make you feel energetic? It was once thought that plants and other substances found in nature heal humans by imparting their “life force”. This concept, known as vitalism, can be seen in everything from Hippocratic medicine, to witchcraft, to the raw food movement. It was the best explanation we had prior to the chemical and biochemical revolutions.
Modern chemistry made it possible to find and isolate active ingredients from these medicinal substances. It turns out chemicals are responsible for the their medicinal effects. Although the term “reductionism” has been used in a derogatory sense to label this explanation of nature - it has undeniably proven to work. Individual chemicals purified from plants retain all the activity of the whole plant. For example, Caffeine is responsible for the energy imparted by the Coffee plant, and vitamin C is responsible for treating scurvy with citrus fruits. As I will point out later, it is very important to identify the active ingredient, measure it accurately, and isolate it from other potentially toxic ingredients.
Principle #2 - Everything is made from chemicals
Regardless of what we put in our mouths, natural or not, everything is made from chemicals. Chemicals are the basic building blocks of life. Listed below are the ingredients of a banana by chemical names.
These names probably sound scary to most people; like the ingredients of a Twinkie or a cleaning solvent. Are these banana chemicals bad for you? The answer is - it depends on the dose.
Principle #3 - The dose makes the poison
It is important to know the dose of a chemical because any chemical at a high enough dose can become a poison. Particularly if it is made bioavailable - easily absorbed into the human body. Summed up by sixteenth century Swiss physician Paracelsus: “the dose makes the poison”.
For example, bananas contain the element potassium for which they are famous. If the potassium of a hundred or so bananas were extracted, concentrated, and taken as a supplement it could stop the heart. Because of this, intravenous push of potassium is the preferred agent of assisted suicide and lethal injection. Suppose you were to eat a hundred bananas all at once, would it kill you? Likely not. The body would take hours to digest and absorb the potassium. The peak levels in blood would not reach high enough to kill. Thus, it is only when the potassium from the banana is concentrated and delivered all at once that it becomes lethal. The dose is very important.
Principle #4 - In nature the concentrations of active ingredients are variable
Plants distribute different amounts of chemicals in different parts of the plant. The leaves, the stems, and the roots may differ dramatically in the concentration of a particular active ingredient. The concentration of chemicals also depends on other factors including the different strains of the plant, the amount of light during the growing season, water availability, and the quality of the soil. Thus, from batch to batch, from company to company, supplements can have completely different dosages of the active ingredient. This issue is particularly problematic when purchasing a herbal supplement, like Echinacea or Ginkgo, where the active ingredient has never been identified - knowing the dose is almost impossible.
Principle #5- Plants are not our friends
Plants intentionally produce and concentrate poisons. The disadvantage of plants is that they cannot move or physically defend themselves from predators. Their only defense is chemical warfare. Over hundreds of millions of years evolution has designed the perfect neurotoxins. Caffeine, THC, cocaine, and nicotine are chemicals highly concentrated in certain parts of plants. Their only function in these plants is to kill or ward off insects.
We have learned to repurpose these chemicals into medications by fine-tuning the dosage. We have found their therapeutic windows - the dose that won’t kill us, but has a desired effect. Once again, the dose is very important.
Principle #6 - Supplements have a therapeutic window
“If a little is good, more is better”, has proven to be false in biology. In fact, whether it is penicillin, exercise, aspirin, stress, or vitamin D, there seems to be a sweet spot or therapeutic window. Too little and no effect, and too much will cause side effects (see diagram below). The therapeutic window is determined in a dose titration study. Subjects are given progressively higher dosages to determine response. Many supplements have not been subjected to dose titration studies. Consuming these supplements without a known therapeutic window is a risky undertaking in deed.
Principle #7 - Most chemicals in the body don’t benefit from supplementation
Human primates have a set of essential nutrients that we could not survive without. We must attain them from our food sources. These include 9 amino acids, 2 essential fats, 13 vitamins, and 15 minerals and trace elements. Healthy people in western countries reach the therapeutic window of these essential nutrients from diet alone.
Everything else in your body is synthesized on site from basic building blocks - even complex structures such as DNA, hair, skin, and neurons. This is known as “de novo synthesis”. The food we eat is complex but is broken down into more basic molecules by acids and enzymes in the gut. These basic molecules are then sent via the circulation to parts of the body where they are reassembled into more complex molecules. Therefore, supplementing complex molecules is unlikely to produce results. They would most likely be disassembled in the gut, and end up as non-specific building blocks or fuel for the body. It would not force a specific organ to produce more of that molecule de novo. Your skin is made from collagen; you can ingest all the collagen supplement you want, it’s not going to make your skin younger. Your hair is made from keratin; you can shampoo your head with pure keratin all day long, it’s not going to treat your thinning hair. Your brain is made from DHA fat; you can ingest all the DHA supplements you want, its not going to make you smarter. Yet, this simplified and erroneous view of physiology is pervasive in the supplement world.
Principle #8 - Supplements target complex biological systems
Promoters of supplements claim that supplements can “boost immunity”, “support joints”, “decrease inflammation”, and “improve circulation”. This reduces an entire system to a simple “on” or “off” state, which is either “good” or “bad”. Immunity is good and it should be turned on. Inflammation is bad and must be turned off. Is this how human physiology really works?
Supplements, like drugs, work by targeting a receptor on a cell, or an enzyme in the body. These systems, however, are tightly balanced and linked to other systems. Disruption and imbalance result in a cascade of many effects - some good, some bad, some dependent on the specific patient, and the specific situation. This is a key concept in physiology and is known as “antagonistic pleiotropy”.
The supplement White Willow bark (aka Aspirin), for example, prevents blood from clotting. It does this by inhibiting the COX enzyme. Is prevention of clotting a good thing or a bad thing? It all depends on the patient and the situation. Blood clotting is good if we are skiing and fall, hit our heads, and start bleeding into our brain. Blood clotting is bad if our blood vessels are lined with sticky cholesterol plaque.
Echinacea, as another example, claims to “boost the immune system”. However, the immune system has many subsystems, hundreds of cell types and thousands of signaling chemicals (cytokines). So which part does Echinacea actually “boost”? And what is the entirety of its consequences? Suppose the whole immune system was “boosted”, is that a good thing? Too much immunity can lead to inflammation, autoimmunity, allergy, and clotting of blood.
The biochemistry of the human body is a large delicate interdependent web. The complexity appears greater the deeper we go. Our current knowledge is superficial at best. Beware of simple explanations.
Principle #9 - All chemicals have side effects - even chemicals derived from nature
In the eighteenth and nineteenth centuries, all medications were from natural sources. They included herbs, metals, minerals, tonics, extracts, purgatives, laxatives, etc. Most were very toxic. They could kill infections, for example, but caused so much collateral damage that the cure was worse than the disease. Ironically, a patient was more likely to survive in a homeopathy hospital receiving nothing at all but water and sugar pills. In fact, the toxicity of nineteenth century natural medications is likely to blame for the popularity and proliferation of homeopathy in Europe and the US.
But out of failure comes innovation. The goal of doctors became the discovery of a “Magic Bullet”, a term coined by Paul Ehrlich in the early 1900’s. A magic bullet was a medication that only targets the disease, sparing the rest of the body. The first antibiotics, like Penicillin, were thought to be “Magic Bullets”. Penicillin was a completely natural product extracted from the mold Penicillium. It yielded miraculous cures with no collateral damage. Finally, a “magic bullet”! Unfortunately several problems and side effects began to surface including antibiotic resistance, kidney failure and severe allergy. Most recently we have noticed the effect of antibiotics on the microbiome. The good bacteria are collateral damage. Penicillin is not so “magic” after all.
Approximately 50% of modern prescription medications are derived from natural sources. Penicillin, Statins, Taxol, Colchicine, Digoxin, Quinidine, Metformin, Botox, Lidocaine, hormones, Opioids, to name a few. All have side effects and some are quite lethal. It is exceedingly difficult to produce a true “magic bullet”. Beware of claims of no side effects and do not underestimate the complexity of human physiology. If it is powerful enough to heal, it is powerful enough to harm.
Supplements contain concentrated chemicals. The identification and measurement of which is essential to determine dosage. Supplements target complex biological systems with a cascade of potentially good and bad effects. Before purchasing a supplement, try to ascertain the following:
Has the active ingredient been identified?
Is the dose of the active ingredient listed?
Has the therapeutic dose range been determined?
Do you get enough through diet?
Are there other unknown or unmeasured chemicals in the supplement?
How does the supplement work in the human body?
Could the supplement cause any harm?