BUILDING STRONG BONES


By Stanford Field
Spring 2003

THE STORY

This is a story about building bones that will encompass the chemical structure of bone, how it is made by the body and what is required to build strong bones. The human body is a remarkable arrangement of interrelated biochemical systems that are constantly striving to approach the dynamic equilibrium that is required for life. When these systems are functioning optimally, we are in a state of good health. It is under that condition that the biochemical entity can be anabolic to grow and maintain itself with repairs. Thus, anabolic conditions throughout the body are a basic requirement for building strong bones. Various stresses of all kinds inhibit anabolism. So, what does it take to build strong bones?

BONES: WHY DO WE HAVE THEM?

The skeletal system performs the following functions:

• Support: The skeleton provides a framework for the body and, as such, supports soft tissues and provides points of attachment for skeletal muscles.
• Protection: Internal organs are protected from injury by the skeleton. For example, the brain is protected by the cranial bones while the heart and lungs are protected by the ribs and sternum (breastbone) .
• Movement: Skeletal muscles are attached to bones. When muscles contract, they pull on bones and together they produce movement.
• Mineral Balance: Bones store minerals, especially calcium and phosphorus, that can be distributed to other parts of the body, on demand, to maintain balance.
• Blood Cell Production: In certain bones, a connective tissue (red bone marrow) produces blood cells (hemopoiesis). Red bone marrow consists of immature blood cells and macrophages. Marrow is found in the pelvis, ribs, breastbone, backbones, skull, ends of the arm bones and thigh bones.
  

 

WHAT IS BONE?

Bone tissue contains a great deal of intercellular substance called "matrix" that is surrounded by widely separated cells. The matrix consists of inorganic mineral salts (mainly calcium and phosphorus salts) which make the bone hard, and organic collagen fibers which give bone its flexibility and strength.

Special cells called "osteoblasts" form collagen and bone while other cells called "osteoclasts" actually tear down old, worn or injured parts of the matrix as part of a remodeling process that removes old bone and replaces it with new tissue. After the osteoclasts have finished tearing down the old matrix, the osteoblasts deposit matrix salts around the collagen fibers of the matrix. The tissue then hardens in a process called "calcification." A delicate balance is maintained between the action of the osteoclasts in removing calcium and collagen and the action of the bone-making osteoblasts in depositing calcium and collagen. That balance is hormonally controlled, for the most part.

Bone is not completely solid. It has channels for blood vessels that supply the bone cells with nutrients. Bone is classified as "compact" or "spongy" depending on the size and location of the spaces.

 

WHAT IS COLLAGEN?

Collagen is a major protein in the human body. It constitutes about 25-30% of total body protein - more than half of which is found in bone. Collagen fibers are very tough, yet they allow some flexibility. These fibers occur in bundles which provide great strength. Collagen fibers are found especially in bone, cartilage, tendons and ligaments. Collagen gives blood vessels strength.

Collagen starts out as a linear chain of amino acids that consist mainly of glycine, proline, and lysine. In the next step toward collagen, the proline and lysine are hydroxylated in a process that requires vitamin C, bioflavonoids and ferrous iron. The hydroxylated proline and lysine attract water to provide flexibility.

After hydroxylation, three of the amino acid chains spiral around each other to form a long helical protein fiber (like multistranded rope). Then glucose and galactose sugars are attached to some of the hydroxy groups on the proteins (glycosylation). The procollagen is then moved outside the cell into the extracellular matrix. It is transported to its final position where it is cross-linked into mature collagen. Bone collagen is extensively cross-linked to maximize rigidity. Collagen cross-linking depends on copper which is in an equilibrium with zinc in an approximate weight ratio of 10-20 zinc to 1 copper.

 

WHAT IS CARTILAGE?
 
Articular cartilage is the major connective tissue capping the ends of bones around a joint. Cartilage provides smooth surfaces for unrestricted joint movement and acts as the principle shock absorber during times of impact on the joint.

Cartilage is made up of a dense network of collagen and elastic fibers imbedded in a firm matrix of proteoglycans, water and chondrocytes. The proteoglycans are made up of a protein core and complex amino-sugars (glycosaminoglycans - GAGs). Three principle GAGs found in joints are hyaluronic acid, keratin sulfate and chondroitin sulfate. "Chondro-itin" is derived from "chondro" which means "cartilage" and "itin" which means "substance." The function of GAGs is to increase lubrication of the joint and provide shock absorption by incorporating water molecules into the matrix. Glucosamine is an important raw material used by chondrocytes (cells of mature cartilage) to build GAGs. Glucosamine can repair structural joint damage. However, the rate of repair is lengthened if further damage is inflicted.

 

WHAT IS OSTEOPOROSIS?

Osteoporosis is a net loss of bone mass and flexibility. A principal effect of aging is the decreased ability to form collagen from the organic matrix part of bone. At the same time, calcification is becoming an increasing part of the bone. This combination causes bone to lose its flexibility and become more brittle. Small holes appear making the bone weaker and porous. Osteoporosis is underway. In females, from age 40 to 70, as much as 40% of bone calcium is lost if no counteractive measures are taken. In males, bone calcium loss typically begins after age 60. The disorder may cause pain (especially in the lower back), loss of body height and eventually, bone fractures.

Another medical term is "osteomalacia" which is the abnormal softening of bone. In this disease, there is a marked loss of calcium in the bone matrix which results in weakness, pain, broken bones, loss of desire to eat, and associated weight loss. The lack of minerals in the bone is caused by a poor diet or the poor absorption of minerals and nutrients from the intestines. In addition, there is probably a deficiency in almost all other variables that effect bone growth.

 

BUILDING STRONG BONES

The principles that follow are applicable to people of all ages. However, the elderly (50+ years) have the most problems as "aging" begins to dominate. The variables to be discussed include the following:

• Diet: The diet supplies the raw materials for bone building. However, the endocrine and nervous systems coordinate the functions of all body activities to determine how the raw materials will be used. The control of diet and chronic stress are important factors that determine whether anabolic (building) or catabolic (breaking-down) conditions are occurring in the body. Bone-building and any other constructive activity requires a body that is in an anabolic condition.
• Supplemental Nutrients: These are required to supply not only additional raw materials for bone- building, but also the additional biochemicals that are needed to effect the innumerable chemical reactions necessary for health.
• Exercise: Moderate exercise provides the positive stress that causes bones to strengthen. Lack of exercise weakens muscles and bones.
• Intake of Toxics: Toxins can disrupt hormonal signals, inhibit chemical reactions and prevent bone- building.
• Detoxication: It is necessary to continuously detoxicate body poisons to maintain an anabolic condition.
• Sleep: Deep sleep (reflected by low cortisol levels) is the opportunity for the body to rejuvenate itself to enable anabolism.
  

DIET

Hypothalamic sensitivity (in the brain) is necessary for all hormone production and control. That sensitivity is diminished by chronic stress (excessive cortisol) and enhanced by calmness, patience and a sense of well-being. The stresses associated with aging cause rising cortisol levels and associated loss of hypothalamic responsiveness. Aging is also associated with a chronic catabolic state that makes bone-building difficult.

With that preamble, we can now turn to the effect of diet on hormone control. The hormone glucagon promotes positive cell hormones (eicosanoids), while excess insulin produces negative cell hormones (eicosanoids). The control of glucagon and insulin is in your diet. Excess cortisol (generated from chronic stress) stops the production of both positive and negative eicosanoids which inhibits some of the negative effects of diet, but at the same time, prevents positive results.

The main dietary factors that promote glucagon dominance (positive) are:

• Hypocaloric diet (eat slightly less calories than used - calorie restriction). Severe calorie restriction (speedy loss of weight and low final equilibrium weight) will create physical and psychological stress, secretion of excess cortisol, physical damage, and a dramatic drop in libido and testosterone. Aim for a Body Mass Index (BMI) of 20-25. Begin an isocaloric diet at BMI = 20-22. BMI = (weight in Ibs.)(703) / (height in inches)².
• Weight loss to achieve a BMI of 20-25 should be constrained to an estimated 5-10% per year to maintain homeostatic balance and to allow the body to slowly burn fat without secreting excess cortisol. A more rapid rate of weight loss will create excessive cortisol which will convert muscle to glucose, increase hunger as the first step in the storage of fat and the weight rebound that drastic dieters often experience. Even so, slow weight loss will be difficult for many people because in today's world, we want everything to happen instantly -- another high stress maker!
• Diet should contain about 60 grams per day of protein for a 160 lb. person who exercises moderately 3-4 times per week (scale proportional to weight). The protein source should be mainly fish because cattle meat is contaminated with hormones [estradiol, diethylstilbesterol (it is banned but still used because no one polices its use) and growth hormones, pesticides [hormone disruptors) and antibiotics). Do not eat farmed salmon because they are contaminated with PCBs (put in the salmon feed grain while in storage to prevent bacterial and fungal infestation), antibiotics which are given because the salmon are crowded together in pens and contaminated with feces that can cause diseases, and linoleic acid (carcinogenic) derived from the grains they are fed. The farmed salmon fat is high in linoleic acid rather than the healthy omega-3s of wild salmon.

Some diets recommend eating all the protein you want with no restriction on calories. That kind of diet causes rapid weight loss. So where's the catch? Too much protein can lead to cardiovascular disease, chronic renal failure and Alzheimer's disease. A dietary imbalance between too much methionine (methionine is high in protein) and a deficiency of methylating and detoxifying nutrients (B6, B12, folic acid, trimethylglycine and choline) leads to an accumulation of homocysteine - a powerful oxidant that causes arteriosclerosis - which is the underlying cause of disability and death from vascular disease that affects the heart and brain. At the same time, an eat-all-you- want high protein diet causes metabolic acidosis and chronic renal failure that leads to kidney dialysis and death.

The diet should contain enough fat and complex carbohydrates to maintain the goals of achieving the desired BMI. Fat type should be restricted to olive oil, coconut oil, medium chain triglycerides and a tablespoon per day of uncontaminated cod liver oil. Do not use hydrogenated oils (essentially all supermarket oils) or margarine. Those oils are decidedly harmful to health. Consuming most of your carbohydrates from fresh vegetables allows the control of insulin which is vital to being healthy. Avoid all sugar and high glycemic load foods. The glycemic load concept is far more important than glycemic index, as shown in the following table:

INSULIN CAN BE CONTROLLED BY REDUCING GLYCEMIC LOAD

	Insulin- stimulating carbohydrate (grams)	Glycemic Index (glucose = 100)	Glycemic Load (amount x index)
PASTA (1 cup)	38	59	2240
APPLE (one)	16	54	860
BROCCOLI (one cup)	3	50	150

Be sure to eat enough fiber to slow the digestion process and to promote bowel elimination and detoxication.

The main dietary factors that promote insulin dominance (negative) are:

• Hypercaloric diet (eating more calories than used - gaining weight). As the hypercaloric eater gains weight, the person loses the will and the ability to exercise. Health gets progessively worse. At the root of the situation is usually a diet that is high in simple carbohydrates, high in sugar, high in glycemic load and low in fiber. That kind of diet combined with chronic stress leads to insulin resistance - then diabetes, early aging and early death. Carrying the excess weight for a long time destroys cartilage. The comes all the pain killers. So, forget about building strong bones.

STEROID HORMONES

Many interacting hormones, controlled by the hypothalamus, are involved in both bone-building (by osteoblasts) and bone resorption (dissolving of bone by osteoclasts).  The hierarchy of hormones is dominated by cortisol (secreted by the adrenal glands) which is determines whether the overall body condition is anabolic or catabolic. When excess cortisol is secreted (eg. during an acute starvation episode), the body converts protein from muscles to glucose to keep the body alive. This destructive condition is decidedly catabolic. Chronic stress is the most destructive of all pro-inflammatory and pro- aging forces. An excess of cortisol will inhibit anabolic processes and will accelerate catabolic processes. Building strong bones cannot take place when a person is chronically stressed. To the contrary, chronic stress will contribute to osteoporosis.

The key anabolic steroid hormones are testosterone (dominant in men) and estrogens (estradiol. estrone and estratriol) and progesterone (dominant in women). The dominant catabolic hormone is cortisol for both men and women.

An excess of estrogens in either sex suppresses protein synthesis and cellular energy metabolism. Excess estrogens suppress the activity of both osteoclasts (they dissolve old bone) and osteoblasts (they build new bone). Excess estrogens produce old and brittle bones even though they have maintained some degree of density. The bone density test may be misleading because it cannot distinguish between brittle and flexible bones. Testosterone and progesterone stimulate both osteoclasts and osteoblasts, producing younger, stronger, denser and more flexible bones. Incidentally, the removal of the uterus and ovaries (ovarian hysterectomy) produces substantial bone loss that can be partially offset by progesterone and testosterone supplementation.

When progesterone supplementation doesn't increase bone growth in women with osteoporosis, it's usually because they have low testosterone or high cortisol. High cortisol, depression and bone loss are closely linked.

As a man or woman ages, the anabolic hormones decline, while cortisol rises. Thus, in going from young to old, the ratio of catabolic to anabolic hormones increases steadily. A younger biological age can be achieved by supplementing with anabolic hormones and developing a lifestyle that emphasizes tranquility and calmness.

Chronically high cortisol wreaks havoc on all structural tissues of the body causing a breakdown of skin, muscles, bone and the immune system. Excessive cortisol activates osteoclasts that dissolve bone (speeding bone loss) and inhibits osteoblasts (slowing or stopping bone replacement and new bone growth). Furthermore, excess cortisol inhibits the absorption of essential minerals such as calcium, phosphorus and magnesium, and, excess cortisol causes an expression' of the aromatase enzyme which converts androgens to excess estrogens.

 

RATS IN A MAZE

The American lifestyle of frantic time schedules, long working hours, sedentary work, fast food and the endless pursuit of pseudo-ego-enhancing material goods has created a general state of high chronic stress. We live in a world of high speed information that incessantly bombards us with stimuli that overload any brain. Chemical pollution is a major factor stressing bodies of all ages. This state of chronic stress is reflected in the rising rates of chronic diseases that pervade our society.

Those of us who do not want to be sucked into this societal whirlpool can take action by seeking the peace and serenity of nature, music, art, meditation, reflection of life's accomplishments, contemplation of future achievments, and by sincerely being friendly, compassionate and understanding. The tranquility that comes with that path is linked with health as reflected in a strong immune system, lower blood pressure, longer life and ... stronger bones.

 

ENVIRONMENTAL HORMONE DISRUPTORS
 
The phenomenal rise of the chemical industry during the 20th century has been a marvel to experience. The use of plastics in all parts of everyday life has provided great utility and comfort. The use of pesticides in the agriculture industry has greatly improved productivity, while at the same time, lawns and golf courses were made beautifully green.

Concurrent with the chemical era has been an incessant rise in non-infectious disease rates of all kinds. The pharmaceutical industry responded by creating a multitude of drugs that inhibit biochemical pathways to suppress symptoms of disease. Consequently, conventional doctors began to dispense the drugs because conventional medicine is based on the diagnosis of symptoms and their subsequent suppression. The reasons for disease are rarely relevant to its diagnosis and treatment.

A small group of doctors have begun to understand that much of the rising disease rates are attributable to environmental chemicals, and that we have been lured into a Faustian bargain. These environmentally-oriented doctors are practicing medicine based on the diagnosis of symptoms and their cause. Treatment starts with diet changes, the use of supplemental nutrients and detoxification of the body.

Environmental chemicals that act as hormone disruptors attach themselves to hormone receptor sites throughout the body. In the case of testosterone and estrogen steroid hormones, the hormone disruptor chemicals saturate the steroid receptors. The hypothalamus receives an erroneous feedback that signals natural steroid hormone availability is sufficient. The hypothalamus then slows additional testosterone and estrogen production by reducing the amount of luteinizing hormone sent from the pituitary to the testes (in men) and to the ovaries (in women).  The hormone disruptors are now in control. They suppress protein synthesis, cellular energy metabolism and bone building. Environmental testosterone and estrogen mimics increase sex hormone binding globulin (a protein in the blood that stores sex hormones) which takes active testosterone and natural estrogens out of circulation - thus reducing the anabolic activity of the body.

It is important for the senior part of the population to maintain adequate amounts of anabolic hormones throughout the body in an attempt to thwart the negative effects of environmental hormone mimics. This is most easily done by supplementing with physiological amounts of natural hormones. They are available, by prescription, as creams or gels that can be absorbed transdermally.

 

MORE HORMONES

The body controls biologically active (ionized) calcium in the blood plasma in a very tight range of 44-52 mg/l by interacting with protein-bound calcium which acts as storage. Suppose you drink a can of dilute phosphoric acid that is sweetened with sugar (called a "soft drink"). What happens? The body uses its alkaline resources that include calcium and magnesium to neutralize the acid. The calcium and magnesium are then excreted in the urine. To restore balance to the system, the parathyroid gland secretes parathyroid hormone (PTH) which causes increased reabsorption of calcium in the kidneys, dissolving of calcium from the bones (spine first), and an increase in calcitriol (a vitamin D) which increases the absorption of calcium from the gut. Imagine what happens when the next can of cola comes down the hatch - unbalanced cycling that throws the various systems into chaos and wears out the hormonal glands, kidneys and bones. Chronic diseases occur when the body is forced into wide-swinging adjustments to external inputs in an attempt to achieve balance.

 

VITAMIN D - ANOTHER HORMONE

The main function of biologically active vitamin D (1,25 - dihydroxyvitamin D3) is to maintain adequate plasma levels of calcium. It performs this task by increasing the uptake of calcium by the intestines, minimizing the loss of calcium by the kidneys, and stimulating the dissolution of bone (in the presence of PTH). Activated vitamin D (1,25 dihydroxyvitamin D3) can also increase the availability and use of calcium and phosphorus for proper mineralization of the skeleton.

In addition, activated vitamin D has remarkable anticarcinogenic effects. It has been found to induce redifferentiation (reversion of cancer cells back to normal cells) or to inhibit cell proliferation in a number of malignant cell lines (in vivo) including human prostate cancer cells. Activated vitamin D suppresses growth of colon cancer, malignant melanoma and renal cell carcinoma. The hormone induces apoptosis of cancer cells by downregulating the bcl-2 cancer gene and upregulating the p53 apoptosis gene. Apoptosis is genetically programmed cell death if the cell is not viable.

Vitamin D can be produced from the prohormone, cholecalciferol which is synthesized in the skin from 7-dehydrocholesterol via photochemical reactions using ultraviolet B (UV-B) radiation from sunlight. Since sunscreens inhibit UV-B penetration, one should stay in the sun without sunscreen and without getting sunburned (use olive oil or coconut oil to keep the skin moist).

Everyone should also supplement with cholecalciferol. The best sources of that prohormone are cod liver oil, salmon oil and other cold water ocean fish and their oils. About 50-80% of ingested cholecalciferol is absorbed. The elderly are especially at risk for vitamin D deficiency because of inadequate exposure to sunlight, inadequate intake of vitamin D-containing foods and the use of drugs which interfere with the absorption and metabolism of vitamin D.

After intestinal absorption, cholecalciferol is processed by the liver to make 25-hydroxyvitamn D (biological activity being discovered) which is then sent to the kidneys where magnesium is involved in the conversion to the main biologically active hormone, 1,25-dihydroxyvitamin D3. Reserves of the hormone are stored in the liver and kidneys where the half-life is about 28 days.

The Recommended Dietary Allowance (RDA) which is usually very low because the the government is prescribing one dosage for 250 million people is 400 IU (10 mcg) per day. I have been taking one tablespoon of cod liver oil daily for many years. One tablespoon is 14.4 grams, and It contains 1380 IU (35mcg) of the vitamin D prohormone, cholecalciferol which will become 1,25-dihydroxyvitamin D3 after passing through the liver and kidneys. In addition, a tablespoon of cod liver oil contains vitamin A (14,400 IU), EPA (eicosapentaenoic acid) at (1500 mg) and DHA (docosahexaenoic acid) at (1380 mg). All of those nutrients are needed to for health.

Some people cannot digest cod liver oil. The problem may lie with an inadequate supply of stomach acid and digestive enzymes (especially lipase which digests fats). So, they could try betaine hydrochloride and digestive enzymes along with the cod liver oil. If that doesn't work, they could make salmon an important part of their diet (do not eat farmed salmon because they are heavily contaminated with polychlorobiphenyls [PCBs]).

 

ADDITIONAL SUPPLEMENTAL NUTRIENTS
    
The following suggested protocol should be approached to the extent that you can.

• Betaine Hydrochloride and Digestive Enzymes: Most elderly people have low stomach acid and have difficulty with digestion. Using the betaine hydrochloride and digestive enzymes will enhance your ability to digest what you eat as well as the supplemental nutrients that you take.
• Multivitamin: Use a full spectrum vitamin.
• Multi-B vitamins: Use a full spectrum vitamin.
• Antioxidants:
• Fat-soluble: vitamin E mixed tocopherols (400-800 IU/d); tocotrienols; CoQ10 (100 mg/d); mixed carotenes.
• Fat and Water-soluble: alpha lipoic acid.
  
• Water-soluble: vitamin C (3000-6000 mg/d) as calcium or magnesium ascorbate. Do not use ascorbic acid.
• Bioflavonoids; Selenium; Green tea extract.
• Vitamin K:  This vitamin distributes calcium to the bones. If vitamin K is deficient, calcium is deposited in the arteries contributing to atherosclerosis. Vitamin K is necessary for proper blood clotting and it should not be taken by those taking blood thinners such as heparin and warfarin. Use 5 mg/d of vitamin K. The RDA of vitamin K is 80 mcg/d which is 0.8% of what recent recommendations are.
• Vitamin A: This vitamin contributes to the control of the activity, distribution and coordination of osteoblasts and osteoclasts.
  

Minerals: Calcium, magnesium and phosphorus are in a complex three-way equilibrium with each other. Too much of one causes the excretion of the others. The goal is to seek balance. Strive for 400-800 mg/d of each of the three, as food and supplements. Do not use calcium carbonate (found in many supplements and antacids). It is essentially rock that is hard to digest and absorb. Furthermore, it contains lead which is highly toxic. Use a calcium-magnesium citrate supplement which is 1/1 Ca/Mg and is much more easily absorbed. Do not drink milk because it probably contains antibiotics, hormones and pesticides that need to be detoxified. Milk also has a Ca/Mg ratio of about 10 which is highly unbalanced. Nuts are good sources of magnesium and phosphorus. Liquid supplements are available that contain 600 mg Ca, 300 mg Mg, and 300 mg P per tablespoon. Animal and fish are sources of phosphorus, but too much of those foods can cause an excess of homocysteine which is an underlying cause of arterioscerosis.

Zinc, copper, boron, manganese and silicon are vital to bone building. Zinc (30-60 mg/d) is required for the formation of osteoblasts and osteoclasts, and for the synthesis of various proteins found in bone tissue. High levels of zinc are found in white and red bloods cells, skin, bone, kidneys, liver, pancreas, retina and prostate. Copper works in balance with zinc and vitamin C to form elastin, an important component of all muscle fibers. Copper (3 mg/d) is needed to strengthen blood vessels and it is involved in bone mineralization. Boron (3 mg/d) is required for the conversion of vitamin D to its active form and for the incorporation of calcium, magnesium and phosphorus into bone. Boron also reduces the urinary excretion of calcium and magnesium. Manganese (10-15 mg/d) is required for the absorption of calcium into bone. Silicon (4-6 mg/d) is needed to build bone and cartilage. It makes the skin hold more hydroxyproline, an amino acid needed to prevent wrinkling and sagging.

 

MODERATE EXERCISE

Between the ages of 20 and 70, people lose about 30% of their muscle mass. Moderate exercise strengthens ligaments, tendons, muscles and bones as the body adapts to the requirements imposed by the exercise. In sedentary activity, muscles shrink rapidly and they become weaker. Without mechanical stress, bone does not remodel normally because resorption outstrips bone formation. Bones weaken through demineralization and collagen reduction. Astronauts subjected to the weightlessness of outer space lost as much as 1 % of their bone mass per week. Their protocol now includes mechanical stress exercises. Care must be taken when implementing an exercise program. Injuries occur when a deconditioned body is pushed to do too much. 

 

DETOXICATION

To maintain a strong, healthy body, it is necessary to continuously detoxicate normal metabolic poisons. Furthermore, it is absolutely necessary to minimize the accumulation of environmental chemicals that are poisoning us.

Detoxication in the body takes place in two distinct phases:
   
Phase I of the detoxication process takes lipophilic (fat-soluble) molecules and makes them water-soluble (polar). This task is effected by oxidoreductase enzymes that transfer electrons to and from fat-soluble toxins. These enzymes are collectively called the "cytochrome P450 enzyme system." They are typically found anchored to the membranes of the endoplasmic reticulae and the mitochondria within cells. Cytochrome P450 enzymes are responsible for all molecules that require conversion to water-soluble forms including food-related toxins, most drugs, steroid hormones, neurotransmitters, eicosanoids, bile acids and caffeine. Food pesticides and fungicides have been shown to inhibit cytochrome P450 enzymes.

The water-soluble molecules from Phase I detoxication are reacted with chemicals in the Phase II group that are catalyzed by Phase II enzymes called "transferases." The transfer reactions that occur in Phase II detoxication are typically referred to as "conjugation" reactions because of the joining together of Phase I-activated toxins and Phase II chemical groups. There are five basic types of conjugation reactions in Phase II. They are as follows:

• Sulfation - Uses glutathione (a tripeptide consisting of glutamic acid, glycine and cysteine) and other sulfur sources such as methyl sulfonyl methane (MSM) and dimethyl sulfoxide (DMSO). Glutathione is generally regarded as the most important thiol (-SH) in humans. Glutathione can cause cancer cells to redifferentiate to normal cells. Glutathione is part of the chemotaxis effect that allows immune system phagocytes to engulf and digest microorganisms, cellular debris and foreign particles.
• Methylation - Uses methyl groups from molecules such as trimethylglycine (TMG), trimethylaminoethanol (choline), dimethylaminoethanol (DMAE), and dimethylsulfoxide (DMSO). Methylation deficiency has been linked to schizophrenia, Alzheimer's disease, Parkinson's disease, depression, cancers and general aging.
• Glucuronidation - Uses glucuronic acid from a chemical such as calcium-D-glucarate.
• Acetylation - Uses an acetyl group from a chemical such as acetic acid (vinegar). The body's energy system has an abundant supply of acetyl groups in the form of acetyl coenzyme A.
• Acylation - Uses one of three amino acids (glycine, glutamine or taurine).
  

 

TOO LATE SCHMART is written by Stanford Field (BS chemical engineering, 1951) who has been avidly studying biochemistry and physiology, since 1993, with an aim of staying healthy despite the ever-increasing odds of age-related decline. This publication is written to the best of his ability, and it is intended to document any findings that may be useful to interested readers. The publication has neither profit nor political motives.

Spring 2003
All rights reserved.