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From the Townsend Letter
June 2013

Rethink Health: Inflammation Is Actually Repair Deficit: Using Physiology First to Achieve Better Outcomes
Part 1: Value and Importance of Understanding Inflammation As Repair Deficit Opportunity
by Russell Jaffe, MD, PhD, CCN, and Jayashree Mani, MS, CCN
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An Integrative Approach to Restore and Repair
Better clinical outcomes incorporate new insights from molecular biology. The Alkaline Way of living is the clinical program or plan that best concurrently enables healthy immune, neurohormone, digestive, and detoxification system functions. The Alkaline Way includes the following four interdependent elements:

1.  Functional Tests
Functional lab tests are suggested that are primary and predictive. Measures of energy metabolism, inflammation, detoxification, oxidative stress, metabolic status, cell communication, acid/alkaline balance, and immune system function are included because they are interdependent. Functional and predictive measures of loss of tolerance to food and environmental chemicals can now be determined by lymphocyte response assays (LRA by ELISA/ACT) that are among the breakthroughs included in this personalized approach to risk reduction.

2.  Healthful Eating and Drinking
An alkalinizing eating plan establishes repair by maintaining healthy cell and body pH levels. There is a Food Effects on Body Chemistry chart that guides more healthful consumption. The Joy of Eating the Alkaline Way is available as a free downloadable summary or a purchasable e-book that includes details of speeding a tasty transition from foods that wear you out to foods that sustain and restore. High-fiber, healthier digestive transit time, enhanced detoxification, improved intestinal repair and function, and increased intake of essential nutrients are all woven into this approach.

3.  Supplementation
Individualized supplement protocols or flow charts address inflammation starting with specific nutrient deficits to make sure that the essentials that cannot be made are present in the amounts needed and in the right places for each individual. The level of toxins in the environment, the reduction in nutrient density in what most people eat, the intensity of distress, sedentary lifestyle – all add up to supplementation, often intensive supplementation, until repair deficit inflammation has been resolved.

Essential and conditionally essential nutrients are required to maintain or restore health rather than elective. Fortunately, using the predictive biomarker tests below, we can now personalize the nutrients needed, confirm the level of risk reduction through repeat tests, and confirm to individuals how much healthier they are on supplements that are needed for sustained health or to restore health.

4.  Healthy Thinking and Doing
Lifestyle choices with an emphasis on activity and mindfulness are geared towards enabling healing responses. Sitting for more than 20 minutes at a time turns out to be among the least healthful activities, particularly for digestion, circulation, and joint health. We suggest a timer that alerts the individual every 20 minutes to get up, stretch, look outside, or at least imagine that you are looking outside and appreciate whatever you have just accomplished or are making progress toward. A few deep abdominal breaths and whatever general and gentle stretching feels best. In addition, 20 minutes twice a day of mindfulness practice to cultivate awareness and nonattachment is an investment in long-term healthy equanimity.

Each step of this approach is described in greater detail below starting with the independent predictive biomarkers that allow each person to know status of key control systems in the body so that you can determine if you are getting all that your body needs to keep you as healthy as possible.

Functional Tests: Predictive Biomarkers
The following functional markers are predictive of outcome and useful in monitoring therapeutic outcomes and responses. These tests have been chosen because taken together they cover the major aspects of metabolism. In addition, these tests have been done on large enough populations and with long enough follow-up that results from these predictive biomarker tests can be translated into years or decades of life at risk, retainable, or reserved depending on the individual's tests results. In addition, we suggest interpreting each individual's tests results compared with the best outcome value for the biomarker. The seven tests that follow have been selected as most predictive and most actionable if test results are not at their goal or best outcome value:

  • Sugar, energy, metabolism: Hgb A1c, fuctosamine, glycation products tests
  • Inflammation: hsCRP, sedimentation rate (sed rate), fibrinogen, ferritin, tumor necrosis factor (TNF), certain cytokines and microalbumin, among other inducible proteins
  • Detoxification and methylation status: Homocysteine
  • Oxidative stress, free radical activity and antioxidant status: Oxidized LDL/HDL & 8-oxo-guanine
  • Metabolic status and acid/alkaline balance: 1st urine pH after 6+ hours rest
  • Cell communication: 25-OH vitamin D
  • Immune tolerance or reactivity: LRA by ELISA/ACT tests

While most labs report a usual or "normal" range for lab results, this information is of use for comparative, statistical but not predictive, clinical purposes. The test value can be used to calculate the years or decades of life either gained or lost, depending on the value for the test obtained for that individual. Predictive biomarker tests are referenced or interpreted based on goal value. For more details, visit

We find that use of goal values represents the best current predictors of health risk or resilience. These tests can be influenced by epigenetic lifestyle actions to influence all-cause morbidity and mortality. Predictive biomarker test results allow a comprehensive yet accessible, actionable personalized, comprehensive health plan. Best outcome goal values are also useful in comparative effectiveness research where objective discriminators are needed when comparing complex therapies in the community.

Best outcome or goal values (GV) follow:

  • Hgb A1c < 5 mg/dl
  • hsCRP < 0.5 mg/L8
  • homocysteine < 6 µmol/L9
  • oxidized HDL/LDL10 and 8-oxo-guanine11 ~0
  • 1st AM urine pH12 6.5–7.5
  • Vitamin D13 (25-OH D) 50–80 ng/L
  • LRA by ELISA/ACT tests; "healthy" means complete tolerance and no delayed allergies

Note that the healthy or goal values above are based on least risk rather than statistical calculations. This means that reported usual or normal ranges for the above tests on lab reports will be different. Usual or normal ranges tell little or nothing about individual relative risk. "Normal" or "usual" lab ranges are calculated and really only reveal if a person is sicker than the population used to standardize the test. Since ambulatory people not known to have the problem are used to establish reference "normal" or "usual" ranges, you only get statistical information. This is useful in distinguishing groups or populations. Unfortunately, since healthy, asymptomatic people are not used to standardize tests, all you really get is information compared to a population. Determining test sensitivity, specificity and predictive index were the best that could be done until functional or predictive tests became available.14

Predictive biomarker test values are consistent with the concept of "optimum" or "high level health" values championed by Cheraskin and Ringsdorf or the individual needs for nutrients pioneered by Roger Williams.15,16

Testing Delayed Allergies: Functional LRA by ELISA/ACT Tests Is Predictive
Delayed allergies are another indicator of a burdened or imbalanced immune system that can contribute to many of the chronic and degenerative illnesses already discussed. Various clinical tests have been used to assess individual adverse responses to environmental antigens.17 Antibodies capable of inciting a delayed response include IgM, sIgA, IgA, and IgG as well as immune complexes and T cell reactions. Serology (antibody) tests are often misleading because they do not distinguish helpful from harmful antibodies. Functional tests such as lymphocyte response assays (LRAs) do not suffer from this methodological limitation.

Limitations of Common Delayed Allergy Tests
IgG antibody assays are performed to detect immunoglobulin G (IgG).18 This has the advantage of examining the system's immunologic memory. Note that most IgG antibodies are helpful, neutralizing, and protective. Only a minority of them are harmful, symptom provoking, and bad.19 Our estimate is that at least 80% of IgG antibodies are helpful and that less than 20% are harmful. More importantly, tests that do not distinguish helpful from harmful results are of limited predictive significance at best. IgG protective antibodies from childhood infections are helpful and not signs of "delayed allergy" to the infection.

Four subclasses of IgG have been identified, which have different biologic functions and vary independently in different clinical conditions.20,21 Clinical interpretation of total IgG antibodies against a specific antigen can be a challenge.22 IgG1 is considered to be primarily for response to bacteria and accounts for 60% to 75% of all IgG. IgG2 is considered to be primarily for response to mucosal or respiratory infections and foreign antigens that access the same areas and accounts for 20% to 30% of all IgG. IgG3 is considered to be primarily for response to atypical substances and accounts for 5% to 8% of all IgG. IgG4 is usually the smallest fraction with the function of balancing specific IgE to reduce or prevent histaminic reactions including to parasites, accounting for just 1% to 4% of total IgG. Only IgG4 is cytophilic for mast cells.23 Thus, some IgG antibodies are protective and others harmful; quantitative serology tests do not distinguish between them.24

Quantitation of IgG antibodies omits information about IgA, sIgA, IgM, immune complex, and T cell offenders while needing multiple subclass assays to provide any predictive clinical information.25 In practice, IgG test results show high rates of false positive and false negative results. This hurts patient compliance and limits successful outcomes.

Immune complex or complement fixation tests can be done in a variety of ways, each with its own methodology limitations.26

Automated cytotoxic tests attempt to identify delayed allergies but only look at cell size change, giving the impression that lymphocytes are tested when any particle of a predetermined size is actually being measured. Understandably, these tests have low reproducibility and offer only short-term benefits.27

LRA Tests Are Functional, Predictive, and More Evidence Based
LRA by ELISA/ACT and MELISA tests both assess reactions of lymphocytes exposed in the lab to different substances but are different by design. Through the technology breakthrough involved in the LRA by ELISA/ACT methodology, it is possible to allow living white cells to react in the laboratory just as they do in the body.28 This determines true delayed allergy/hypersensitivity based on the body's long-lived memory-carrying white blood cells. LRA by ELISA/ACT tests are also unique in that all 3 delayed hypersensitivity pathways are measured on the same specimen and at the same time. The clinical results are more true positive and few false negative reactions confirmed in multiple successful community-based controlled outcome studies.29,30

The acute and delayed allergy pathways are depicted in the "Wheel of Immune Response Mechanism" (Figure 2).31

Figure 2

By testing lymphocyte reactions to purified antigens, it is possible to accurately assess the burden on immune defense and repair systems. The LRA by ELISA/ACT functional tests have a 97% accuracy rate substantially better than static, nonfunctional IgG testing and other automated cytotoxic, particle size procedures that give ambiguous results at best.32,33

The upstream causes of autoimmunity include acquired reactions to foods or other chemicals to which the body had become hypersensitive during times of distress, marked by enhanced antibody, immune complex, or T cell lymphocyte white cell responses that increase activity yet decrease functional benefits.

Part 1 of the this article has focused on the superior value of functional rather than static, conventional tests to guide advanced, personalized care. Predictive biomarker tests are suggested as an objective means of determining resilience or risk for each individual. Part 2 will present suggestions of what actions to take based on this evidence and synthesis for better outcomes with greater value and lower costs.

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