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From the Townsend Letter
July 2013

Rethink Health: Inflammation Is Actually Repair Deficit: Using Physiology First to Achieve Better Outcomes
Part 2: The Alkaline Way is a Synthesis of Synergistic Healthful Habits
by Russell Jaffe, MD, PhD, CCN, and Jayashree Mani, MS, CCN
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Part 1 is also online

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Part 1 presented a deeper understanding of acute inflammation as repair deficits and chronic inflammation as cumulative repair deficits including the use of independent predictive biomarkers to objectively assess each individual's resilience that can add or risk that can cost decades of quality life. Part 2 presents ways practical, practicable, evidence-based ways of eating, drinking, thinking, and doing that can sustain or regain years to decades of quality life.

A metabolically alkaline diet means that what is consumed, assimilated, and eliminated enhances metabolic function and cell repair resilience.34

Metabolic effects can be different from the food's physical chemistry.35 For example, citrus fruits are alkalinizing because the metabolism of citrate, malate, succinate, and fumarate generates more than twice as much bicarbonate buffer as there is acid itself in the food.36 This means that citrus fruit and similar foods are acid in the food yet alkaline forming in the body.

Dietary sugars, especially isolated fructose and refined flours, are triggers of inflammation driving hyperinsulinemia, leading to a biochemical cascade that alters gene expression, promoting inflammation, and downward spiral into further inflammation and insulin resistance.37

A diet high in sugars and pro-inflammatory omega-6 edible oils (soybean, safflower, canola, and corn oil) and low in fiber and anti-inflammatory omega-3 sources (fish oil, borage, flax seeds, and purslane) contributes to the net acid excess and triggers systemic inflammation.38,39

The primary goal of the Alkaline Way approach is to reverse intracellular acidosis because it impairs electron transport, reduces energy production, and impedes detoxification.40 Immune responses directly and indirectly generate substantial amounts of acidic products.41 In the vulnerable patient with impaired buffering capacity, the sine qua non of metabolic acidosis, it is especially important to avoid as many sources of antigen-induced or other causes of optional metabolic acid production acid as possible because of their adverse effects on cell metabolism.42 First morning urine pH is the predictive clinical tool to assess risk of net acid excess, also known as metabolic acidosis. Comprehensive venous blood gas measurement is the reference standard for confirming metabolic acidosis.43
Anti-Inflammatory Pro-Repair Nutrients: Rescue Nutrients Deplete First
Low-level nutrient and antioxidant deficiencies promote inflammation. We discuss here the role of antioxidants, buffering minerals, and detoxifying and energizing nutrients. For adequate repair and inflammatory support, the following nutrients are essential especially when dietary consumption patterns provide insufficient amounts.

Antioxidants and Oxidative Risks
Antioxidants prevent cell death from excess oxidation. Antioxidants accept and transfer electrons so that the cell can usefully extract energy from the electrons and restore the high-energy work molecule of the cell known as ATP (adenosine triphosphate). Healthy cells have 100 times more ATP than ADP (ademosine diphosphate). The high level of ATP creates a large potential of energy that can be used as needed. In contrast, when the ATP level or ratio falls, the cell switches from elective protective functioning to survival mode. In essence, the cell stops expending energy to protect itself and does only what is needed to survive. In the better case, antioxidants are restored and the flow of life energy returns. In the worse case, a slow decline into chronic, degenerative, self-attacking ill health occurs.

When antioxidants are depleted or unavailable, electrons get free. Free electrons or free radicals oxidize and damage essential cell elements. Beneficial fats, cholesterol, enzymes, and cell structural elements can all be harmed by free radical oxidation.

Below are the more important antioxidants and ways that you can determine the quantity of antioxidants needed for each individual.

Ascorbates: Antioxidant supplemen­tation including ascorbate provides protection from oxidative damage, restores cell energy production, rehabilitates mitochondria, and resets homeostatic mechanisms.44 Another goal of repletion is to reverse cumulative antioxidant deficits often observed clinically as inflammation.

Ascorbates must be in the L-ascorbate form, reduced and buffered with alkalinizing minerals such as potassium, magnesium, calcium, and zinc. Intake is determined by the personalized "C Cleanse" protocol (, which also serves as an effective detoxification tool.
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Ascorbate is needed in large amounts because it acts directly, while true vitamins are needed in small amounts to activate specific enzyme catalysts. This means that ascorbate gets used up in proportion to total oxidative stress. Ascorbate is the central recycling antioxidant that protects and regenerates other active molecules, enhances ATP levels, and sets the cell redox or electrochemical potential. Ascorbate does so many helpful things in the body, it is becoming clear why the needed amount varies more widely between people than any other essential nutrient. Fortunately the C Cleanse allows us to find out how much ascorbate individuals need to stimulate repair and respond to their oxidative stress.

We find some highly healthy people require less than 4 grams per day, while some with high degrees of oxidative stress require over 100 grams per day, in both cases to achieve the same tissue level of ascorbates, the difference due to functional half-life for ascorbate of 30 days in healthy people and 30 minutes in the least healthy.

Polyphenolics: Quercetin dihydrate and soluble or low molecular weight (LMW) orthoproanthocyandins (soluble OPC or LMW OPC) with or without freeze-dried pomegranate juice work synergistically with, yet separately from, ascorbates.

Quercetin is a family of bioflavonoids found in most fruits and vegetables. There are thousands of quercetins in nature. Quercetin dihydrate is the safer and more effective quercetin that has been shown to improve vascular functions in diabetics, reduce blood glucose levels, and have prorepair, antiatherogenic effects.45 Anywhere from 0.5 to 50-plus grams of quercetin dihydrate, coupled with soluble OPC and pure pomegranate juice extract (if needed), provides superior oxidative stress reduction, protects the cellular machinery, and activates repair.46 Meals containing bioactive polyphenolics are available.47

Fully buffered ascorbates and flavonoid/flavonol complexes described here work synergistically, and are antihistaminic and hormone sparing.48 Quercetin dihydrate and reduced glutathione both enhance reduction of dehydroascorbic acid (oxidized ascorbate) back to fully reduced ascorbate.49
B-complex, Folates, PABA, Biotin, and Betaine (TMG):  The entire team of B vitamins and the substrate betaine are required for healthy methylation. Impaired methylation is reflected in elevations in homocysteine above the healthy value of <6 µmol/L. Problems with cell communication, detoxification, and transport result from impaired methylation. Adequate B complex, including folates, paraaminobenzoic acid (PABA), biotin, betaine, or trimethylglycine (TMG) is important as methyl donors or for methyl group transfers. Betaine also contributes to healthy stomach acid production. Betaine intake from 50 to 500 mg per day is usually sufficient.

Colorful Carotenoids: Mixed natural carotenoids such as alpha- and beta-carotene, zeaxanthin, cryptoxanthin, lutein, astaxanthin, and lycopene are better than synthetic beta-carotene.50 Each carotenoid has a different and specific helpful function in the body. All are needed. None are redundant. Large intake of synthetic beta-carotene is discouraged. Large intake of mixed natural carotenoids in diet and supplements is encouraged, while taking isolated single forms such as beta-carotene alone are not recommended. We suggest 11 to 55 mg/day of mixed carotenoid intake.

Tocopherols (Vitamin E): Vitamin E is a family of 8 forms (alpha-, beta‑, gamma-, and delta-tocopherol and alpha-, beta-, gamma-, and delta-tocotrienol). Some of the eight members of the vitamin E family share similar functions, and others have functions that are completely different. Mixed natural tocopherols, at least 800 to 3200 IU, are recommended for decreasing oxidized LDL and cholesterol, platelet aggregation, and increasing vasodilation.51 Intake sufficient to keep cholesterol and other polyunsaturated fats oxidation from occurring is recommended. Intake of synthetic single-form vitamin E is discouraged. Taking more than 400 IU of d-alpha-tocopherol is discouraged based on recent studies.

Vitamin D3: Vitamin D3 deficiency can lead to elevated levels of inflammatory markers such as hsCRP, IL-2, IL-6, and insulin resistance. Sufficient amounts of cholecalciferol in medium chain triglycerides (MCT) oil are indicated to maintain levels of 50 to 80 ng/ml.52

Buffering Mineral Ratios and Acid Displacement
Minerals are essential for survival. Mammalian cell metabolism makes more acid than bicarbonate buffer. This means that the cell will die from metabolic acidosis and programmed cell death unless the essential buffering minerals are taken in through the diet. The mineral uptake system, particularly for calcium and magnesium, is subject to inhibition. Newer approaches to enhance mineral uptake are described below.

Potassium and Sodium: Whole foods contain mostly potassium and much less sodium. Processed foods almost always strip out the potassium and add sodium. Potassium is important to keeping cell machinery functioning. Sodium is kept outside cells except when they contract. After contractive action, the cell then has to pump the sodium out, at high energy cost to the cell. In general, if people doubled their potassium intake and halved their sodium intake by eating more whole and fewer processed foods, their health would markedly benefit due to the reduction in chronic metabolic acidosis.

Whole foods provide minerals in the alkalinizing citrate, fumarate, succinate, and/or malate or similar functional forms that lower blood pressure and enhance health. Processed foods contain much chloride, sulfate, and other acidifying salts that raise blood pressure and reduce health.

Magnesium, Calcium and Choline Citrate: Calcium and magnesium are the amplifying second messengers for most hormones and neurochemicals. Calcium says "go!" Magnesium says "relax." The usual intestinal uptake enzyme, the calcium magnesium ATPase, is easily and often inhibited or partially blocked due to exposure to toxic metal and/or persisting pollutants. Fortunately, a recent discovery allows for enhanced magnesium mineral uptake through the concurrent use of choline citrate. While no other form of choline works, choline citrate in vegetable glycerin enhances magnesium uptake. This is particularly important because today's diets tend to have too much calcium and too little magnesium. Indeed, most of what drives calcium mineral loss from the body is an even more severe magnesium cell deficit. We suggest intake of 500 to 1200 mg/day of calcium and 400 to 1200 mg/day intake of magnesium in bioavailable forms that do not cause diarrhea or intestinal distress.

Zinc and Copper: Zinc and copper balance each other at an optimum ratio of 20 to 1. Healthy function depends upon enough of these minerals, particularly zinc. Immune, hormone, neurochemical detoxification, and digestion health depend on a healthy zinc to copper balance. We find intake of 10 to 100 mg/day of zinc and 1 to 5 mg/day of copper optimizes the function of both zinc- and copper-dependent systems for most people.

Chromium and Vanadium: Chromium (0.25–1.5 mg/day as the citrate or picolinate) and vanadium (0.25–1.5 mg/day as the ascorbate) are essential for healthier sugar metabolism. Acting separately, they both help improve insulin function and blood sugar levels.

Molybdenum and Manganese: Molybdenum is essential to activate the enzyme that converts irritating sulfite into sulfate. Manganese is needed for healthy energetics. Some people need 10 to 100 mg/day of manganese when their energetic mechanisms are highly active or challenged by environmental toxins. While large-scale, long-term safety trials of the preferred forms of manganese have not been done yet, the safe upper limits calculated by groups such as the Institute of Medicine at about 10 mg/day are based on an absence of data rather than data on harm at higher intakes. It is also clear that some people need much more than the average to meet their biochemical and metabolic needs. It is also clear that people living near manganese smelters have higher incidences of mental and physical health challenges; however, this may be due more to the ore being smelted than the manganese itself.

Selenium and Strontium: Seleno­methione (Se-met) is the preferred form of selenium supplementation. Se-met metabolism is closely linked to protein turnover. In this organic and natural form of selenium, there is no toxicity as in other synthetic forms, and it is beneficial to the body.53 A healthy dose of 50 to 1000 mcg/day is recommended. Selenite and selenate are more toxic and less effective and not recommended.

Stable strontium is required for healthy bone formation. While at high doses strontium can compete with calcium uptake, we recommend physiologic intake of strontium (50–100 µg per day) as one of the many minerals assimilated. At this low, physiologic level of intake the stable strontium does not interfere significantly with uptake of other minerals such as calcium or magnesium.

Iodide and Iodine: Iodide and iodine are needed for thyroid and other hormone function. In balance, both forms are needed as part of healthy Alkaline Way living. We recommend regular intake of sea vegetables and/or supplementation to provide at least 1 mg/day of iodine and iodide.

Detoxification and Metabolic Energetic Essentials
Biodetox: The increasing load of persistent organic pollutants such as PCBs and pesticides as well as heavy metals such as arsenic, mercury, and lead has been linked to inflammatory conditions such as diabetes and insulin resistance, in part through increased cytokine production.54,55 Detoxification can begin through foods. Superfoods such as garlic, ginger, onions, broccoli sprouts, and eggs (GGOBE;
Figure 3) provide the body with minerals, especially sulfur and sulforaphane, an organosulfur compound, and support healthy detoxification systems. Sulforaphane exhibits anticancer, antidiabetic, and antimicrobial properties. These foods are also a rich source of IP-6 that aids in the metabolism of insulin and calcium; promotes healthy hair growth, bone marrow cell metabolism, and eye membrane development; and helps the liver transfer fat to other parts of the body.

Figure 3

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