Medical Biochemistry 101

From my previous posts, I have highlighted the importance of nutrition on human performance.  The typical medical approach for “preventative” illnesses is to provide medications rather than identify and address root cause. There are several reasons for this approach, but the data trends are demonstrating that this method is failing our patients. In my last post, Let Me Be Clear, I had listed many physicians and researchers that have had tremendous success with improving metabolic health through a nutritional approach.  Our ad libidum Standard American Diet (SAD) has significantly disrupted normal intended bodily biochemical processes and created physiological dysfunction. Biochemistry can explain development of many of these processes, which I will highlight in this blog.  Hypertension (high blood pressure), hypercholesterolemia (high cholesterol), type II diabetes mellitus, gout, peripheral artery disease, non-alcoholic fatty liver disease (NAFLD) and obesity all share a common origin. 

There are several genetic disorders (familial hypercholesterolemia , Niemann-Pick Disease, etc.) or other pathological conditions (Cushing’s Syndrome, Multiple Endocrine Neoplasia Syndromes, etc.) that do not follow these patterns.  Fortunately, acquired pathological conditions and genetic diseases are quite rare. As you will see, most of these diseases manifest from carbohydrate consumption, mainly fructose, which is predominant in processed and convenient foods. Interestingly, there are significant subsidies for junk food (and here) and diseases are linked to consuming subsidized commodities. I have mentioned before that the American Medical Association and American Hospital Association are perennially top financial contributors to the federal government in lobbying funds. At some point, we have to question the intent of our medical associations and the federal government.  As patients continue to get sicker and physicians suffering more burnout, with no good answer to reverse any of this, we are headed in a bad direction.

Metabolic Syndrome diagnosis requires having three or more of the following criteria:

  • Large waist: Men with a waistline >40” and women with a waistline >35”
  • High triglycerides: >150 mg/dL
  • Low HDL-C: Men <40 mg/dL and women <50 mg/dL
  • Increased blood pressure: >130/85 mmHg
  • Elevated fasting glucose: >100 mg/dL

Unfortunately, we rarely address conditions for our patients prior to achieving this level of metabolic dysfunction. There are several other subtle laboratory findings that should be scrutinized (some of which the insurance won’t pay for), to assess for worsening metabolic health, prior to achieving fulminant metabolic syndrome. Subtle changes in metabolic health can be assessed through ALT (>25), uric acid (and here) >5.5, triglyceride:HDL ratio (here) , fasting insulin level (>15 mIU/L) and an oral glucose tolerance test (here) to evaluate for insulin hyper secretion (if fasting insulin levels are normal). Our threshold diagnosis for Metabolic Syndrome is akin to our diagnosis of many types of cancers. Many cancers have rapidly advanced prior to their detectability, which makes them difficult to cure.  By the time we have reached the diagnosis threshold of Metabolic Syndrome, the disease has progressed to a level that is difficult to reverse. The strategy has been to identify each of the metrics independently and treat each of them with a medication, failing to recognize a common origin in the majority of patients.

Biochemistry is a discipline of chemical substances and vital reactions in living organisms.  The study is the combination of cell biology and physical chemistry involving sustainment of life. Enzymes, are proteins, used to facilitate reactions, and help to create a homeostatic equilibrium in response to external stimuli.  Some of the most understood biochemical reactions surround carbohydrate metabolism.  Fructose (5-membered ring monosaccharide only metabolized in the liver) metabolism has been demonstrated to be the most disruptive to cellular functioning.  With the addition of high-fructose corn syrup in processed foods that eliminate fiber and add sugar into our diet, our health has not been so poor.  Removal of sugar from the diet ameliorates many of these ailments (given that the patient is not suffering from any genetic disease or other pathophysiological condition leading to inappropriate functioning).

Hyperuricemia, is taught in medical school to come from red meat or alcohol consumption, but this is a small percent of how we create uric acid. Uric acid, the crystals that cause gout, is a byproduct of purine (nucleic acid) metabolism. When fructose is introduced into the hepatocyte (liver cell), it is immediately phosphorylated (energy given in the form of phosphate donation) by adenosine (purine) triphosphate, through the enzyme fructokinase, creating an adenosine diphosphate (ADP).  This ADP is then converted to adenosine monophosphate (AMP) through the adenylate kinase enzyme.  AMP has two destinations, it can either become dephosphorylated by adenosine kinase into adenosine or could be phosphorylated to become ADP and the fate of AMP is reliant upon the activity of AMP kinase (AMPK)which is activated when cellular ATP (energy) is low.  In the fed state, energy levels are high and insulin, in addition to high ATP levels, promotes the creation of adenosine and ultimately metabolized into uric acid (see diagram). Elevated uric acid is intimately associated with increased blood pressure and risk marker for cardiovascular disease by the disruption of nitric oxide synthase and affecting production of nitric oxide that relaxes arterial smooth muscle tone. Disruption of nitric oxide synthase causes vasoconstriction and elevation in blood pressure.

In addition to the increased uric acid production, insulin is an anabolic (promoting growth and proliferation) hormone secreted from the pancreas in response to carbohydrates or, to a much smaller degree, branched-chain amino acids. Insulin stimulates many pathways in the body, promoting energy storage and growth. Glucose storage is the most acknowledged role of insulin, but it also inhibits AMPK, inhibits fatty acid mobilization, promotes fatty acid storage (in the form of triglycerides), promotes glycogen synthesis, indirectly stimulates mTOR (enzyme complex in growth and proliferation) and promotes renal sodium absorption which causes an increase in blood pressure. Although insulin is vital for cellular functioning, too much insulin contributes significantly to diseases of civilization (atherosclerosis, NAFLD, type II diabetes mellitus, obesity, gout, hyperlipidemia, coronary artery disease, etc.). 

There are two types of diabetes mellitus (DM), type I and type II.  Type I DM is characterized by beta cell destruction in the pancreas, leading to hyperglycemia as insulin is imperative to activate GLUT receptors on the cell surface for glucose to gain entry into a cell.  If insulin is absent, glucose accumulates in the blood and cannot be used for cellular energy.  This is an example of internal starvation and ketone bodies are generated from lipolysis (fatty acid metabolism) at such high concentrations, to provide energy for cells, that it can create a decrease in the pH leading to a pathological, sometimes fatal, condition known as ketoacidosis. Giving insulin to these patients (in a controlled fashion to prevent electrolyte imbalance) is life saving. Type II DM, conversely, is a disease characterized by hyperinsulinemia (until pancreatic exhaustion), insulin resistance and obesity.  Obesity is a symptom of disease, not the cause. Insulin is an anabolic (growth and storage) hormone that contributes to energy storage and appositional growth after osseous physeal arrest (closed growth plates). Foods and other stimuli that increase plasma insulin levels will result in growth or fattening. Restriction of such agents will cause the opposite effect. Adoption of a low-carbohydrate, high-fat (healthy fat, coming from real food sources), modest protein diet will ameliorate these conditions, which you will see evidence of from my previous blog (here). 

It has been reported that 88% of the US population is metabolically unhealthy. This number continues to climb by the substances we continue to eat. Packaged and processed food is easy (readily available), cheap (due to government subsidies), quick, has a long shelf life (due to addition of sugar and other preservatives) and is flavorful (due to added sugar). The addition of sugar in the diet, primarily fructose, with the subtraction of soluble and insoluble fiber has led to the health demise of our population and akin to smoking unfiltered cigarettes. The pharmaceutical industry has financially triumphed at the expense of our worsening health, without a reversible solution. Healthy living isn’t achieved by the addition of numerous medications. Health is achieved by the subtraction of the offending agent. With all of the evidence I have presented in my previous blog, Let Me Be Clear, and experienced through my own personal dietary changes, I have no reason to suspect otherwise and the science corroborates this hypothesis. Added sugar and subtraction of fiber from our food creates and perpetuates disease. Even seemingly packaged “healthy foods” have hidden sugar in them as there are 262 names used in processed food and beverages. Until these “foodlike substances” are removed from our diets, we will not be able to adequately address metabolic derangement and the addition of numerous medications will continue to be a game of chasing our tail.

Published by Blakemillerdo

I am an orthopedic trauma surgeon that has become disillusioned by our traditional medical system as I do not believe it works well for the people it is designed to help. We have lost our vision and the cost of care for the product is unacceptable. This site has been designed to help elucidate problems in medicine and help direct a change for our patients!

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