Info I read

[Guest guest]

The Detoxx System: Detoxification of Biotoxins in Chronic Neurotoxic

Syndromes

By , M.D., Kane, Ph.D., Neal Speight, M.D.

Chronically ill individuals suffering from neurotoxin exposure

impacts patient populations with CFIDS, Fibromyalgia, MS, Autism,

Cardiovascular Disease, Depression, Rheumatoid Arthritis, IBS,

Infertility, ALS, Parkinsons, Lyme, Toxic Building Syndrome, Estuary

Associated Syndrome, Psychosis, Diabetes without family Hx, Optic

Neuritis, Refractory Heavy Metal Toxicity, Pulmonary Hemorrhage,

Stroke. Patients diagnosed with these chronic illnesses may be

potentially classified as 'Neurotoxic Membrane Syndrome' (NMS) with

the endothelial cell membrane as the target of degeneration.

While hypercoagulation involves a myriad of proteins, it is

ultimately a membrane event, essentially disrupting the phospholipids

that structure the membrane. Agglomeration (blocked cellular exposure

to blood flow/nutrients and impaired cell-to-cell communication)

indicates elevation of phospholipase A2 and the uncoupling of

eicosanoids from the cell membrane causing inflammation. The

agglomeration that eventually occurs is, in essence, a product of a

weakened membrane, and ultimately a disturbed red cell fatty acid

profile.

Clinical Research

We have established a biomedical protocol in our clinics, The

Haverford Wellness Center in Havertown, PA and The Center for

Wellness in Charlotte, NC for patients with neurotoxic illness. Our

biomedical approach is an attempt to reach the systemic nature of

these tenacious neurotoxic syndromes and provide clinically proven

methods that eradicate neurotoxins. Our course of action is that of

freeing the patient of pervasive symptoms of neurotoxic illness in a

noninvasive manner that heals the membrane, and ultimately the body

and brain.

The recent pioneering work of Ritchie Shoemaker, M.D., as

communicated in his book Desperation Medicine and his peer reviewed

papers (Shoemaker 2001), lends strong support to a connection between

Chronic Fatigue Syndrome, Fibromyalgia, Lyme Disease, Pfiesteria

infection and that of numerous Neurotoxic Syndromes.

Biotoxins as Neurotoxins

The presentation of biotoxin exposure often parallels neurological

and psychological impairment due to the interrelationship between the

ENS (Enteral Nervous System) and the CNS. The biliary tree, gall

bladder, and bile formation within the liver serve in the vital

processes of detoxication (disposal of waste products bilirubin,

heavy metals, biotoxins, xenobiotics), lipid metabolism, transport

and digestion (bile acids). Abnormalities of the hepatobiliary system

may involve biliary stasis whereby infectious material or biotoxins

reside within the liver, biliary tree and gall bladder, as a viscous

suspension in biliary sludge.

Biotoxins as bacteria, viruses, parasites, spirochetes,

dinoflagelletes, and fungus may be within biliary sludge often

creating neurotoxins impacting the CNS via the ENS, or the Second

Brain (gut). The occurrence of biliary sludge may be due to prolonged

fasting, low fat intake, high carbohydrate diets or exposure to

pathogens. Restriction of dietary fat may impair biliary flow which

would be contraindicated in attempting to clear toxicity as bile is

paramount to cleansing the body and getting biotoxins and heavy

metals excreted into the fecal matter.

Neurotoxins are minute compounds between 200-1000 KD (kilodaltons)

that are comprised of oxygen, nitrogen and sulfate atoms arranged in

such a way as to make the outside of the molecule fat loving and

water hating. As such, once it enters the body, it tends to bind to

structures that are rich in fat such as most of our cells, especially

the liver, kidney, and brain. Neurotoxins are capable of dissolving

in fatty tissue and moving through it, crossing cell membranes

(transporting against a gradient, particularly with potassium)

disrupting the electrical balance of the cell itself.

As fat soluble neurotoxins move through the cells of the body from

the GI tract to sinus to lung to eye to muscle, to joint to nerve,

whereby they eventually enter the liver and the bile. Once

neurotoxins bind with bile they have access to the liver, the body is

poisoned over and over again as the bile is re-circulated (first

released into the intestine to digest fats, and then reabsorbed).

Neurotoxins cause damage by disrupting sodium and calcium channel

receptors, attacking enzyme reactions involved in glucose production

thereby disrupting energy metabolism in the cell, manufacturing

renegade fatty acids as saturated very long chain, odd chain and

branched chain fatty acids impairing membrane function, stimulating

enzymes (PLA2) which uncouple essential fatty acids from the cell

membrane and impairing the function of the nuclear receptor PPAR

gamma which partially controls transcription (the conversion of

instructions held in our DNA to RNA which then leads to translation

or protein production in the cell).

Heavy Metals reside in Fatty Tissue with Biotoxins

Heavy metals are also lipid soluble and often compound the removal of

biotoxins (Aschner et al 1990, 1998; Dutzak 1991). As has been

observed by many clinicians, often as the patients' heavy metal

toxicity is addressed they are faced with the additional complication

of the presence of biotoxins. Biotoxins and heavy metal exposure co-

exist within the cell membrane and fatty tissue requiring

consideration for both types of toxicity in regard to patient

intervention.

By stabilizing glutathione we in turn impact metallothionein markers

(Nordberb and Nordberb 2000, Ebadi et al 1995, Sato et al 1995,

Kerper et al 1996, to et al 1998), glycoaminoglycans or GAGS

(Klein 1992), methylation, sulfation, hepatic and renal function as

we introduce treatment protocols for detoxication with gentle,

natural modalities that unload cellular toxicity safely. GSH infusion

by fast IV push has been a remarkable tool to unload the body burden

of heavy metals and neurotoxins in both pediatric and adult

populations, without side effects.

Renegade fatty acids as Neurotoxin Markers

Renegade fats as very long chain fats (VLCFAs) that are over

expressed, disrupt the membrane structure. There is a beautiful

geometry to the membrane that is highly sensitive to the size of the

lipid chains. The overall width of the fatty acid portion of the

membrane is ~3 ½ nm which must be maintained for stability. Saturated

or monounsaturated fatty acids with a length of 16 or 18 carbons and

polyunsaturated fatty acids of 18 to 22 carbons are preferred to

permit the structure to maintain optimal horizontal fluidity. VLCSFAs

that range from 20 to 26 carbons force the parallel dimensions

vertically. There simply is not enough room.

The distortion weakens the phosphate bonds that derive their strong

attraction only as long as the phospholipids are parallel to each

other on both sides of the membrane. The cell weakness is then

expressed in leaky attraction to ion channels and receptors which

marginalize cell cytosol fluids and electrolytes with the only option

as early cell death.

The Brain is Comprised of 60% Fat

To view the brain beyond its architecture as a biological

orchestration of the physical and chemical constituents necessary for

performance, we cannot begin to conceptualize without considering the

importance of fatty acids as the human brain is 60% lipid. Dendrites

and synapses are up to 80% in lipid content. Although Arachidonic

acid (AA) has been given a negative association, it is the most

prominent essential fatty acid in the red cell and comprises 12% of

the total brain and 15.5% of the body lipid content.

If AA is depleted by overdosing with marine or flax oil establishing

the balance of the EFAs is profoundly impaired. Often both

prostaglandin one and two series relating to omega six metabolism are

compromised when flax and marine oils are overdosed or lipid intake

is insufficient. When AA, the lead eicosanoid of the body, is

suppressed due to excess intake of omega 3, toxicity or disease the

control circuitry of the body is impaired as is clearly viewed in the

patient's presentation.

Arachidonic acid is preferentially wasted in states of heavy metal

toxicity (Tiin and Lin, 1998) and has been observed to be sharply

suppressed in RBC lipid analysis in states of heavy metal toxicity

(Kane, clinical observation 1997-2002).

The fatty acid cleaving enzyme PLA2

In states of toxicity via biotoxins or heavy metals there is a

dramatic elevation in Phospholipase A2 (PLA2) activity (Verity et al

1994) Increases in PLA2 activity result in premature uncoupling of

the essential fatty acids (EFAs) from phospholipids in the cell

membrane. Accelerated loss of EFA places the patient in a severely

compromised position as that of inflammation which results from the

promiscuous release of AA in the presence of an overexpression of

PLA2. Carbohydrate consumption, as one of the most profound

stimulators of PLA2, must be restricted to control the insulin

response and the subsequent loss of EFAs.

Phospholipids and Neurons

Phospholipids, cholesterol, cerebrosides, gangliosides and sulfatides

are the lipids most predominant in the brain residing within the

architectural bilayers (Bazan et al 1992). The phospholipids and

their essential fatty acid components provide second messengers and

signal mediators. In essence, phospholipids and their essential fatty

acid components play a vital role in the cell signaling systems in

the neuron. The functional behavior of neuronal membranes largely

depends upon the ways in which individual phospholipids are aligned,

interspersed with cholesterol, and associated with proteins.

All neurotransmitters are wrapped up in phospholipid vesicles. The

release and uptake of the neurotransmitters depends upon the

realignment of the phospholipid molecules. The nature of the

phospholipid is a factor in determining how much neurotransmitter or

metal ion will pass out of a vesicle or be taken back in.

Phospholipid re-modeling may be accomplished by supplying generous

amounts of balanced lipids and catalysts via nutritional intervention

and the use of intravenous Phospholipid Exchange (IV Phosphatidyl

choline).

Hypercoagulation and Membrane Integrity

An undesirable course of events in an exposure to biotoxins is

agglomeration in a hypercoagulation state. The distorted membrane

with its weakened structure and almost absolute reduced fluidity is

powerless to resist coagulation. A highly fluid membrane would kick

off an accumulation of oxidized cholesterol; it would not permit it

to attach. This is not the case when the membrane is compromised, as

in much of the patient population affected with neurotoxic illness.

Hypercoagulation is predominantly a non-regulated mass of proteins

disrupting function. When referencing the artery; hypercoagulation

invariably involves the plasmic side of the cell and if endothelial

cells of the vascular system are targeted by a toxin (virus,

neurotoxin, metal, antibody, etc) , restriction of blood flow

ultimately results. If a neuron is targeted then signaling is

disrupted. The presence of neurotoxins invariably involves PLA2,

which is the " sergeant at arms " monitoring cell membrane health. A

membrane disturbance(unwanted mass) would trigger PLA2, which

hydrolyses the release of eicosanoids, which would then induce

inflammation and call to attention the clean-up committee, i.e.

macrophages.

Hypercoagulation is a restrictive agglomeration, (mass) that occurs

principally on the membrane of endothelial cells blocking the flow of

vital fluids, blood, bile, etc., with a high causal relationship to

oxidation, and equally to toxicity, quite often neurotoxins. Oxidized

LDL (Sobel et al 2000) is predominantly a membrane disturbing event

agglomerating and attaching to endothelial cells, while neurotoxins

can move through the lipid membrane and attack the cell itself.

The Liver as the Center of the Storm

Unhealthy bacteria have been known to colonize the liver and its

biliary system. These bacteria as well as viruses, spirochetes,

dinoflagellates, and the like can synthesize very long chain

saturated or renegade fats (Harrington et al 1968, Carballerira et al

1998) that lead to liver toxicity, biliary congestion, impairment of

prostaglandin synthesis and the release of glutathione (Ballatori et

al 1990). Lipids vibrate in the cell at millions of times/second. The

double bonds of the omega 6 and omega 3 lipids are the singing

backbone of life expressed through their high energy level.

These bonds are their vibratory song, and they absolutely carry a

tune befitting every act and function in the exercise of life,

providing all 70 trillion of our cells their flexible nature. When

renegade fats are over represented in the cell membrane they result

in off key expression, and if strong enough, may spell cellular death

and apoptosis. Healing the outer leaflet of the membrane (Schachter

et al 1983), comprised primarily of phosphatidylcholine, with

phospholipid therapy, is our highest priority in addressing chronic

illness and hypercoagulation.

The Visual Contrast Sensitivity Test

Our clinical approach is to first confirm that neurotoxin mediated

illness could in fact be a problem for the patient via the Visual

Contrast Sensitivity test that isolates deficits in velocity of flow

in retinal capillaries. If the patient scores poorly on this test

then the evaluation may include screening for cytokine elevations

followed by coagulation and red blood cell lipid testing through

s Hopkins/interpretation through BodyBio. (For pediatric patients

the Heidelberg Retinal Tomogram Flow Meter Evaluation may be

performed in place of the Visual Contrast Test by an ophthalmologist.)

Neurotoxins and Cytokines

Once neurotoxins enter the cell they move toward the nucleus turning

on indirectly the production of cytokines such as TNF alpha, IL6, and

IL-1Beta (Shrief and 1993, Tsukamoto 1995, Abordo et al

1997,Rajora et al 1997, Brettelal 1989, Hassen et al 1999, son

2001). TNF alpha will stimulate macrophages in the body (macrophages)

to become active. The white cells are also induced to gather in the

area of the cytokine (TNF alpha) release. In addition, TNF alpha

induces endothelial cell adhesion.

Endothelial cells which line the blood vessels of the body

become " sticky " in conjunction with the increase in white cells.

Increased blood viscosity results in restricted blood flow in

neurotoxic patients leading to fatigue and discomfort, and quite

possibly disturbed toxic photoreceptor lipid structures that become

compromised with subsequent reduction in visual performance.

The cellular impact of biotoxin and heavy metal burdens results in

disturbed prostaglandin synthesis, poor cellular integrity, decreased

GSH levels (DeLeve and Kaplowitz 1990, Dentico et al 1995, Hayter et

al 2001, Miles et al 2000, Nagai et al 2002, Zalups and Barfuss 1995,

Watanabe et al 1988, Fernandez-Checa et al 1996), significant

suppression of omega 6 arachidonic acid and marked elevation of

Renegade fats and ultimately with demyelination (depressed DMAs). The

presence of VLCFAs are evidence of peroxisomal dysfunction and

suppression of the beta oxidation of lipids and cellular respiration.

Renegade fats (VLCSFAs, Odd Chains, Branched Chains) are represented

as an increase in fat content in the brain as discovered in stroke

patients examined by Stanley Rapoport, Chief of the Laboratory of

Neuroscience at the NIH. Biotoxins and heavy metals are lipid soluble

thus the effect upon cellular processes and hepatobiliary function is

often gravely deranged. Often, patients do not possess a gross burden

of toxins but rather a burden that has a finite impact upon the cell

by blocking receptor sites such as G proteins, which act as a relay

system through the cell.

Peroxisomes, most prevalent in the liver and kidney, are organelles

within the cell that play a crucial role in clearing xenobiotics and

the third phase of detoxification. Peroxisomes are intimately

involved in cellular lipid metabolism (Bentley et al 1993, Mannaerts

and Van Veldhoven 1992, Luers et al 1990, Leiper 1995) as in the

biosynthesis of fatty acids via ß-oxidation involving physiologically

important substrates for VLCFAs, thromboxanes, leukotrienes and

prostaglandins.

The creation of a prostaglandin is an oxidative event (Diczfalusy

1994). Inappropriate use of antioxidants (mega-dosing) will inhibit ß-

oxidation, the production of prostaglandins and cellular metabolism,

thus the liberal use of potent antioxidants would be contraindicated

in the buildup of Renegade fats as VLCFAs, Odd Chain and Branched

Chains (Akasaka et al 2000) which are the hallmark of toxicity (Kane

and Kane 1997, Kane 1999, Kane 2000, Roels et al 1993, Rustan et al

1992).

Peroxisomal oxidation enzymes are suppressed by elevation of

cytokines such as TNFalpha (Beier et al 1992). Individuals with

immune, CNS, cardiac, GI and endocrine disorders often present with

complex xenobiotics involving disturbances in the cytochrome P450

superfamily (hepatic detoxification difficulties) which parallels

disturbances in peroxisomal function.

The cytochrome P450's are responsible for the biotransformation of

endogenous compounds including fatty acids, steroids, prostaglandins,

leukotrienes and vitamins as well as the detoxification of exogenous

compounds resulting in substantial alterations of P450s (Guengerich

1991) as xenobiotics may turn off or greatly reduce the expression of

constitutive isoenzymes (Sharma et al 1988).

Targeted Nutritional Intervention for Toxicity

Inadequate stores of arachidonic acid can compromise P450 function

(McGiff 1991). Oral application of hormones such as pregnenolone,

DHEA (Di Santo et al 1996, Ram et al 1994, Rao et al 1993) or thyroid

stimulate peroxisomal proliferation and the ß-oxidation of Renegade

fats as would nutrients (riboflavin, pyruvate, manganese) and

oxidative therapies.

Anti-oxidants slow cellular metabolism and must remain in the proper

balance with all the essential nutrients and substrates (lipids,

protein) to maintain metabolic equilibrium. Removal of renegade fats

in the diet is accomplished by the avoidance of mustard, canola oil

(Naito et al 2000), peanuts and peanut oil which contain VLCSFAs that

can challenge patients with liver and CNS toxicity.

The oral use of butyrate, a short 4-carbon chain fatty acid, is of

striking benefit (Fusunyan et al 1998, Segain et al 1983, Yin et al

2001) in mobilizing renegade fats, lowering TNFalpha, sequestering

ammonia, and clearing biotoxins.

In states of toxicity it is paramount to stabilize omega 6 fatty

acids and the lead eicosanoid (Attwell et al 1993) Arachidonic acid

(AA) before introducing omega 3 lipids. There exists a crucial

balance between omega 6 and omega 3 fatty acids in human lipid

metabolism which has only recently been brought into clearer focus

through the work of Yehuda (1993, 1994, 1995, 1998, 2000, 2002). His

development of the SR-3 (specific ratio of omega 6 to omega 3) has

revealed that the optimum ratio of omega 6 to omega 3 FAs is 4:1.

AA, the lead eicosanoid, must be stable first along with the other w6

EFAs before w3 fatty acids are introduced and balanced. Clinicians

are often met with poor patient outcomes when merely administering

omega 3 lipids without first introducing omega 6 fatty acids,

stabilizing the structural lipids, increasing the fat content of the

diet, stimulating the ß-oxidation of renegade fatty acids, flushing

of the gall bladder/biliary tree and supporting digestion of fats

with bile salts and lipase.

The manipulation of lipid distortion involves two basic essential

fats: omega 6 and omega 3. The body loses its ability to metabolize

fats in states of toxicity and therefore becomes depleted in the

eicosanoids and prostaglandins. Essential fatty acids are the

precursors to the regulatory prostaglandins which are " local

hormones " providing the communication controlling all cell to cell

interactions. The human cell membrane cannot be supported nor its

function controlled without respect to lipid substrate, yet fatty

acid metabolism has been poorly delineated in the medical literature.

An optimum balance of fatty acids make up the dynamic membrane. The

membrane of every living cell and organelle is composed of two fatty

acid tails facing each other. This bilipid layer is so minute (3.5

nanometers) that it would take 10,000 membranes layered on top of

each other to make up the thickness of this paper. Yet the dynamics

that occur within this tiny envelope with organelles prancing up and

down the cytoskeleton microtubules is a microcosm that is a challenge

for the human mind to envision. Mercury toxicity damages the

microtubule structure of the cell. All cells must synthesize

molecules and expel waste.

All cells must create, through gene expression, the proteins needed

for cellular gates embedded in the membrane as ion channels and

receptors. The ultimate control of how those peptides behave rests

with the character of the membrane while the integrity of the

membrane rests with the structural (oleic, stearic, palmitic,

cholesterol) and essential lipids (omega 6, omega 3). Without control

of membrane function through lipid manipulation, detoxication is

compromised. In essence, the life of the cell is intimately tied to

health of the membrane and the health of the entire organism.

Our clinical protocol is to initiate treatment with changing the

patients' overall diet, addressing the lipid balance and especially

the outer lipid leaflet of the cell membrane through fatty acid

therapy and the addition of supplementation targeted towards

dissolving fibrin, clearing the liver/biliary tree, and healing the

cell membrane. Patient progress is evaluated through the Visual

Contrast Test and repeat lab evaluation.

Blood thinning agents such as Heparin and Warfarin increase blood

flow around the blocked endothelium, however, reconstituting membrane

fluidity can directly address coagulation in a natural restorative

way. Vibrant healthy membranes will not permit agglomeration. The

high polyunsaturated lipids with a preponderance of

phosphatidylcholine on the plasmic surface precludes undesirable

clumping to occur. Treatment modalities should address dissolving

fibrin and healing the cell membrane.

Spreading Infection

It has been suggested that the use of heparin will address

hypercoagulation. Recent data from JAMA (son 2001) indicates

that the use of low dose heparin may transform a 'benign fungal

infection into a toxic shock-like reaction'. This research was

presented at the 39th annual meeting of the Infectious Diseases

Society of America in 2001 by Margaret K. Hostetter, M.D. of Yale

University School of Medicine (Hostetter 2001 and San-Blas et al

2000).

Hostetter and colleagues found that Candida albicans can attach to

host cells and form invasive hyphae. Low dose heparin utilized in

procedures for hospitalized patients through the practice of heparin

in intravascular catheters may transform C. albicans into a life-

threatening pathogen. Hostetter was able to identify a gene, INT1,

encoding a C. albicans surface protein, Intlp, which was linked with

adhesion, the ability to grow filaments and ultimately virulence of

C. albicans of a systemic nature.

The use of heparin raises the cytokines TNF alpha and IL-6

(son 2001) in addition to Phospholipase A2 (Mudher et al 1999;

Kern et al 2000; Farooqui 1999; Verity et al 1994). Biotoxins which

form neurotoxins, may create a state of hypercoagulation from the

rise in TNF alpha. Consequently, the use of heparin may exacerbate

the hypercoagulation and the neurotoxic condition. The source of the

problem- biotoxins, which have formed neurotoxins creating a state of

hypercoagulation, must be addressed from the context of the

underlying neurotoxic condition and healing the cell membrane.

Evidence Based Clinical Protocols

By stabilizing lipid status with intravenous Phospholipid exchange

and oral EFA supplementation we have remarkable tools to unload the

body burden of neurotoxins ( et al 1982, Cariso et al 1983,

Jaeschke et al 1987, Kolde et al 1992) in both pediatric and adult

populations, without side effects. Oral use of phospholipids in a

Liver Flush is also an effective intervention in addressing

neurotoxic syndromes.

Through isolating individual fatty acids and dimethylacetyls in red

cells we can now examine the cellular integrity/structure, fluidity,

the formation of renegade fats that impair membrane function,

myelination status, and the intricate circuitry of the

prostaglandins. The systemic health of the individual patient may

reached and targeted nourishment utilized through evidence based

intervention which may yield positive patient outcomes.

Healing the membrane is virtually…healing the brain.

> References for this Article

Neal Speight, M.D. may be reached at Center For Wellness in

Charlotte, NC. Kane, Ph.D. at the Haverford Wellness Center

in Havertown, PA. or to obtain the 'The Detoxx Book: Detoxification

of Biotoxins in Chronic Neurotoxic Syndromes' at 888.320.8338 or

856.825.8338

----------------------------------------------------------------------

----------

Dr. Mercola's Comment:

If you are interested in detoxification, I encourage you to check out

the upcoming Detoxx BioMedical Symposium with Dr. Kane. The

symposium will be held in September in both New Jersey and

Connecticut.

----------------------------------------------------------------------

----------