Secrets Of Blood Chemistry Analysis: Integrating Effective Nutrition By Becoming Your Own Health Detective (part 1 of 4)

Pull out your magnifying lens and become your own health detective! Real health is about self empowerment, patient education and applying and understanding principles and strategies that work for you. Healthcare should be about “health” more than just managing disease. Understanding how to interpret your own blood chemistry test can provide you with a tremendous amount of very valuable insight, which ultimately can be used to develop powerful nutritional strategies for improving your health.

This 4 part series of articles will teach you how to do just that: provide you with the basic data necessary to understand what your blood test results mean, and how to use them to develop effective nutritional strategies.

This series of articles is based upon my experience of having interpreted thousands of blood test results over a 15-year period, having founded a blood chemistry evaluation software (www.True.Report), a 165-page clinical reference guide, as well as created a 10-hour practitioner training course on functional blood chemistry analysis.

This series of articles is going to cover many of the basic components of blood chemistry. It should be known that blood chemistry interpretation can become quite complex. Therefore this series of articles is only going to cover the fundamental material.

Advantages & Disadvantages of Using Blood As A Biopsy

The blood has been called the river of life. In it contains the properties that are used by the cells, tissues, glands and organs of the body. I do not view any one laboratory test as being absolute. I view and use use laboratory data as a way to obtain evidence and information. There are a number of valuable laboratory tests, which each in their own right has something unique to share.

Every lab test provides a unique “snapshot” into a particular system or function of the body. These snapshots are limited by time, function, and effect. Different types of tests yield information about a particular system, or unit of measure, relative to a period of time. Due to the homeostatic nature of blood, it isn’t always clear if the quantitative results of a certain blood chemistry marker represents a “problem”, or an “outlying fluke”. For example, a low sodium result could indicate hyponatremia. However, because blood electrolytes tend to be in constant flux, a single sodium measurement of 135 taken on Wednesday morning may not be clinically relevant, especially if you get tested again on Friday morning and the value is now 141. What caused the 135 reading? Low aldosterone on Thursday night? A moderate change in pH? A shift of the sodium in the serum to the tissues? A dissociation with chloride, due to the formation of leukotrienes? Increased urination and urinary sodium loss? Who knows. We can only speculate.

Since much of what is in the blood is very “homeostatic” (the physiological mechanism that maintain equilibration), it can be argued that the blood is not a very reliable thing to be measuring health. Example: if the body takes calcium from bones in order to keep levels high enough in the blood and cells, how can blood calcium be a valid assessment of calcium metabolism? Since blood steroidal hormones can be bound to certain proteins (such as SHBG) and therefore may not make it to cell receptor sites, how can one accurately assess hormonal function in the blood?

These are 2 of several similar questions which effectively question the efficacy of blood as a valid diagnostic test.

In answer to the 2 proposed questions above, let’s look closer at these issues:

Consider that calcium activity can be assessed not by looking only at serum calcium alone, but by multiple factors that are involved in calcium activity such as phosphorous, albumin and Vitamin D. Or even more interesting, consider that serum calcium levels can actually be used to evaluate the activities of other systems of the body such as parathyroid activity, autonomic functions (see Melvin Page) and digestive functions.

What these series of articles will address is what is called “Functional Analysis of Blood Chemistry”. Since the blood contains so many elements of the chemistry of the body, there are endless blood tests that are available. We will discuss the “Functional” interpretation of the fundamental blood test:

• The Metabolic Panel
• The Lipid Panel
• The CBC (complete blood count)

Replace Conventional Laboratory Reference Ranges With Healthy Person Ranges

Laboratory reference ranges are statistical averages, not ideal values. If you want to really get to the origin of your health issues, this is point #1 that must be addressed. Laboratory reference ranges are created from a mean taken from an increasingly unhealthy population of people. In fact, each lab director sets his/her own reference range based upon the population of people tested for that lab. I have seen completely different reference ranges from 2 different Lab Corp facilities, in 2 different cities. Even more problematic is that some reference ranges are completely erroneous. For example, the Lab Corp reference range for LDL cholesterol (0-99), is a statistical impossibility. If you have an LDL level of ‘0’, you’re dead. How can this possibly be the bottom of a reference range? I’ve observed the same problem with LDH (lactate dehydrogenase). And with fasting insulin, a reference range of 0-28 is totally insane. I will personally challenge anyone to find a person with a fasting insulin level greater than 15 who does not have multiple health issues. A person with a fasting insulin of 15 is either pre-diabetic or diabetic. By the time their fasting insulin is 26 they’re already diabetic. And yet these are the references ranges provided by the largest laboratories in the world. What passes for “normal” on a laboratory reference range I find to be very abnormal in many instances, and in some cases, statistically impossible.

By studying healthy people, free from diseases (such as athletes), we can get a better sense of what a healthy reference range looks like. We have to also take into consideration that certain reference ranges may change based on age, gender and sometimes race. A basic example of this is ALP (alkaline phosphatase). Growing children will have ALP values 1-4x higher than adults because this enzyme can derive from the skeletal system. Conversely, in women of post menopausal age, I can predict the probability of osteoporosis with incremental elevations in ALP, especially if combined with mild elevations in HDL cholesterol.

3 Quadrants of Functional Blood Chemistry Analysis

There are 3 quadrants of functional blood chemistry analysis which allow for the most effective assessment and nutritional strategies.

1. Identify biomarker function – Know the function of individual markers. Understand ALL of the potential relevancies of each biomarker. Know the associated organ/physiological/biochemical pathways for each biomarker.
2. Identify individual biomarkers in relationship to other biomarkers (pattern analysis) – Understand the relationship of individual biomarkers with other biomarkers. Example: Insulin, Glucose, Hemoglobin A1C, LDH are all related. Understand significances of these relationships. Example: When glucose is elevated but Hemoglobin A1C and Insulin are low/normal it suggests adequate glucose control, but some other factor is affecting/increasing glucose.
3. Clinical correlation of biomarkers and patterns to individual patient – How does the biomarker or pattern relate to the patient? Example: The underlying etiology and significance of an elevated ALP and HDL cholesterol in a 26-year old male is likely quite different than for a 70-year old female. Knowing how a pattern relates to the individual is significant, because of differences in age, gender, inter-individualistic genetics, and biochemical individuality. In these cases, the 70-year old female likely has some degree of osteoporosis, and the body’s attempt at osteogenesis by raising the level of ALP in bone. A dexa scan confirms the osteoporosis. The 26-year old male most likely does not have osteoporosis, and his elevated ALP is caused by something else. In which case, you investigate further by looking at the other metabolic enzymes, to see if there are hepatic issues of some kind causing the rise in ALP. You also can choose to run an electrophoresis on the ALP to determine which of the iso-enzymes is elevated. Similar results for 2 patients, 2 different causes and courses of action.

Functional Assessment #1: Glucose Homeostasis

I’ll begin with the assessment of glucose and its related blood chemistry factors. I will provide the reference ranges I consider most important for each factor and then discuss them more in-depth.

• Glucose 80-90 mg/dl; 4.5-5.0 mmol/l
• Insulin 1-6 uIU/ml; 7-35 mmol/l
• Hemoglobin A1C 4.8-5.6%
• LDH: 140-200 U/L

Glucose, Insulin, Hemoglobin A1C & LDH

Glucose is sugar in the blood that is the primary source of energy, burned by all cells of the body. Glucose is transported into most cells, either through insulin signaling, or through GLUT vessicle transport. For most cell types, once inside of a cell, glucose is phosphorylated (glucose 6 phosphate), and then enters in 3 possible pathways: glycolysis, glycogen storage or the pentose phosphate pathway. In addition to food intake, glucose levels are also influenced by many different hormones in the body. 8 hormones are capable of raising glucose, and only 1 lowers it. Therefore, several hormonal factors may be involved in elevated glucose readings. The rate of glucose metabolism may differ significantly from person-to-person. For example, hypoglycemics have rapid glucose oxidation, and this is evidenced by their glucose levels falling fast and quickly (typically 2 hours or less) below baseline, when doing a glucose tolerance test. Hypoglycemia is not suitably defined as “low blood sugar”, but rather as the “rapid, excessive and metabolically inefficient oxidation of glucose”.

When glucose levels begin to rise following a meal, the beta cells of the pancreas secrete insulin. Alternately, glucose can diffuse into cells via GLUT trafficking. Under certain conditions, for example during prolonged fasting or during exercise, glucose can enter cells independently of insulin, via the activation of AMPK proteins in cells, which signal GLUT vessicles to mobilize to the membrane, and enable glucose diffusion. Many researchers consider this pathway (AMPK) to glucose entry to be more efficient than insulin signaling, because of the potential adverse cellular and metabolic effects induced by chronic insulin exposure over time. Type 2 Diabetic drugs (such as metformin), and nutraceuticals (such as lipoic acid, berberine, bitter melon) act through the AMPK/GLUT signaling pathway, as does exercise.

Insulin functions to deliver the glucose in the blood to the cells so that energy can be made. Glucose is subsequently metabolized via the glycolysis pathway, leading to the formation of various glucose substrates, and the generation of pyruvate. Thus, insulin is a primary blood sugar-lowering hormone. The higher the amount of glucose in the blood, the more insulin gets released. If insulin levels continue to rise, the cell receptor sites can become de-sensitized, and “insulin resistance” ensues. The result is higher levels of insulin and glucose in the blood. For many years it was believed that giving insulin as a drug to a type 2 diabetic was ideal. However this approach is rife with problems. I’ve covered this subject in THIS ARTICLE.

Hemoglobin A1C is a 3-4 month indicator for the amount of glucose that red blood cells have been exposed to during their 3-4 month life span. The higher the hemoglobin A1C the greater the exposure to glucose. An elevated hemoglobin A1C is an indicator of glycosylation, stickiness. This itself is problematic. Indeed, elevated hemoglobin A1C values are associated with several mortality risk factors, including stroke and cardiovascular disease. Chronically elevated glucose levels, well into the diabetic range >120 mg/dl, and A1C levels >6.5% may feature various adverse complications, over time. Two such consequences are the formation of AGE’s (advanced glycation end products) and the activation of the polyol pathway. AGE’s create metabolic and cellular toxicity, and are considered a core feature of metabolic toxicity associated with type 2 diabetes. The polyol pathway accounts for roughly 30% of the glucose oxidation among type 2 diabetics. In the polyol pathway, glucose is metabolized by aldose reductase, and this forms a toxic and un-metabolizable sugar known as sorbitol, as well as the formation of fructose. This pathway also causes oxidative stress by using up the cellular pool of NAD+, and creating imbalances in the delicate balance of NAD+/NADH. It’s also likely that polyol pathway activation induces elevations in uric acid (a common issue among type 2 diabetics), because hyperuricemia can be directly induced via fructose (fructose induced hyperurecemia). Research also suggests that elevated uric acid can itself induce an activation of the polyol pathway. Either way, this in turn impairs endothelial function, because elevated uric acid inhibits nitric oxide. This sets the stage for diabetic complications, retinal and kidney damage, NAFLD and hypertension.

It is no wonder that ketogenic and modified versions of a ketogenic and/or low carbohydrate diets have shown through meta-analysis research, to greatly benefit type 2 diabetics. The same promise holds true for fasting and intermittent fasting. Its known that the bile acid TUDCA can sensitize insulin receptors by as much as 30%, and that nutraceuticals such as lipoic acid, chromium, vanadium and botanicals such as berberine, and bitter melon can activate AMPK, reduce NAFLD and improve glucose pathways. Benfotiamine can direct glucose into the pentose phosphate pathway (which functions to generate most of the body’s NADPH, as well as ribose), while Pyridoxamine (a Vitamin B-6 analogue) and L-Carnosine can inhibit AGE formation. Nutritional medicine can cover the biochemical basis in every respect of type 2 diabetes. But the patient must be willing.

Remember that the body has numerous hormonal mechanisms for raising glucose: glucagon, epinephrine, norepinephrine cortisol, thyroxine, growth hormone, ACTH and somatostatin, but only 1 hormonal mechanism for lowering it (insulin). High blood sugar may also be related to stress hormone activation. There appears to be a subset of people who tend to have high morning glucose, compared to other times of the day. I’ve even observed this in those on low carb diets, where A1C values are 5.3 or lower. In these cases, there may be hormonal excess in the morning, increased sympathetic activation (leading to catecholamine release), or some other factor. Therefore, you can’t always rely solely on a fasting glucose level to understand what’s going on in these regards.

A diet that is non-harmonious for one’s individual metabolic needs can be a primary cause of dysregulated glucose homeostasis. Dietary sources of sugars and carbohydrates are primary sources for elevated levels of glucose for many people. However, certain types of protein foods can also increase glucose for certain “Metabolic Types”, as I’ve observed over the years. It’s also possible that food allergies or other antigenic immune responses to certain foods can trigger elevations in glucose. This is due to an autonomic nervous system response following an immune reaction. In this case, one of the sympathetic nervous system hormones (such as epinephrine, norepinephrine or cortisol) could be triggering a rise in glucose.

Ideally a person’s insulin level should be quite low, 1-6 uIU/ml; 7-35 mmol/l. The higher the insulin, the greater the diabetic risk, and the greater the risk for cardiovascular disease, and other complications. There appears to be certain “outliers” that are “high insulin secretors”. It isn’t clear if this is a genetic effect, or some type of pancreatic signaling issue, or a receptor resistance effect.

Individuals who are on ketogenic diets may have a related issue of elevated SHBG (sex hormone binding globulin). This is due to the reciprocal relationship between insulin and insulin-like growth factor with SHBG. It may also explain why diabetics tend to have low SHBG (because insulin is higher). When SHBG levels are higher, this irreversibly binds to sex steroid hormones, leading to their inactivation. This is why boron works, it will quickly inhibit or lower SHBG levels, freeing up sex hormones for use.

LDH (lactate dehydrogenase) is a metabolic enzyme. It doesn’t get routinely tested, but I find it to be of interest and use when working with clients who have blood sugar handling irregularities. It’s a useful tracking marker to establish the efficacy of protocols. LDH functions as an enzyme in the interconversion of pyruvate into lactate, under anaerobic conditions, and therefore it is often useful in monitoring blood sugar metabolism dynamics. Low levels of LDH are associated with hypoglycemia, and may reflect B-1 deficiency in some cases. Higher levels of LDH may be related to hyperglycemia, and protocols aimed at AMPK and glucose metabolism may effectively lower LDH. Elevated LDH levels may also correspond to hypoxia, or pseudohypoxic conditions. Among diabetics with anaerobic metabolism (a less efficient metabolic program that uses lactate to generate energy), LDH levels may appear elevated, and this is reflected in circulatory disturbances, such as blueish-ness of fingers and toes. This can be corrected with the appropriate metabolic balancing. Elevated LDH may also be evident of liver cell damage, or possibly in the damage of other cell types. Electrophoresis can be performed to distinguish which tissues feature high or low LDH iso-enzymes.

We will discuss the relevance of triglycerides, GGT, ALT and AST as its related to liver and NAFLD (non-alcoholic fatty liver) in future parts in this blood chemistry series.