Walter J. Crinnion ND SpiritMed

Walter J. Crinnion NDSpiritMed

www.drcrinnion.comwww.crinnionopinion.com

Overview of Oral Nutrients Supplement Protocol Vitamin C – 3,000-12,000 mg daily Multi-vitamin Whey protein powder – 2 tblspns daily Fiber (RBF/Psyllium) – 3-7 caps at night with H2OHydrochloric acid – with mealsUrine alkalinizing supportProbioticsIn between chelation cycles—support with additional

minerals and mixed traced elements. Extra magnesium is generally needed and has been found to beneficial. (Zn, Se, other ALA)

Ascorbic Acid to Support Heavy Metal DetoxificationVitamin C – 3,000-12,000mg dailyAntioxidantReduces toxicity of heavy metals

JAMA 1999; 281:2289-2293

Adults in the highest serum ascorbic acid tertile has an 89% decreased prevalence of elevated blood lead levels compared with adults in the lowest serum ascorbic acid tertile

Conclusions Our data suggest that high serum levels of ascorbic acid are independently associated with a decreased prevalence of elevated blood lead levels. If these associations are related causally, ascorbic acid intake may have public health implications.JAMA 1999; 281:2289-2293

Ascorbic AcidEnhances CYP functionEnhances incorporation of Fe into hemePrevents nitrosamine formation in GI tractXenobiotics increase AA excretion

Smoking decreases 40% One cigarette 55-200 mg

Sugar 50% decrease

2003

Vitamin C and DMSAWhen given in conjunction with DMSA the

hepatic GSH and catalase levels were restored more effectively than with just DMSA alone.

Vit C given at a dose of 25 mg/kgThat is only 1750 mg for a 70 kg male

Flora SJS, et al. Chem Biol Interactions 2003;145;267-80. PMID 12732454

Nutrients to Support Heavy Metal Detoxification

Magnesium (500-800 mg from Magnesium Citrate-Malate)

This is one of the most commonly deficient nutrients in the toxic patient. Individuals who tend to retain chemical and heavy metal toxins were found to excrete a high amount of Mg in their urine, and have difficulty maintaining proper Mg levels.

Mg deficiency leads decreased amounts of Cytochrome-450 and NADH cytochrome reductase, which are essential to proper functioning of Phase-1 biotransformation.

Mg deficiency leads to low GSH levels

Magnesium40% of CS pts at EHC-Dallas deficientDeficiency leads to:

decreased amounts of CYP450 & NADPH cytochrome reductase (knocks out Phase 1)

Decreased levels of GSHDecreased ATP production Decreased hydroxylation of anilineDecreased methylation of aminopyrine

Supplementation reverses these effectsMills BJ, et al. Proc Soc Exp Biol Med 1986;181:326-32 PMID:

3945642

Magnesium Deficiency S&SMigrainesEyestrainMuscle weaknessFatigueMild myopathyMyopiaIncreased ammoniaHypertension

Muscle spasmConstipationArrythmia, PVCChocolate cravingsKidney stones (with

B6)PMS (with B6 and

potassium)InsomniaDepression

Magnesium deficiencyCadmium toxicity leads to magnesium deficiencyCadmium, lead and mercury may cause or exacerbate

magnesium deficiency, especially for pregnant womenCertain drugs (xenobiotics) lead to reduced RBC

magnesium levels.ROH acts as magnesium diuretic (prevented by Vit E)Homeocysteinemia leads to Mag depletionKobylec-Zamlynska B, et al. Ginekol Pol 1998;69(12):871-7 PMID 10224744Semczuk M, Semczuk-Sikora A. Med Sci Monit 2001;7(2):332-4 PMID 11257745Steidl L, et al. Magnesium 1987;6:284-95 PMID 3129621Rivlin RS. J Am Coll Nutr 1994;13(5):416-23 PMID 7836619Li W, et al. Neurosci Lett 1999;274:83-6 PMID 10553943

Magnesium supplementationSupplementation with magnesium and B6

resulted in decreased RBC levels (increased excretion) of cadmium and lead64 mg elemental Mag and 5 mg B6 per tab, 5 per day

Magnesium supplementation increases GSH levels

Mg is a competitive inhibitor of Cd and Pb and a non-competitive inhibitor of Hg.

Kozielec T, et al. Magnesium Res. 2004;17(3):183-8 PMID 15724866Kedzierska E. Ann Acad Med Stetin 2003;49:131-43 PMID 15552844Mills BJ, et al. Proc Soc Exp Biol Med 1986;181:326-32 PMID 3945642Guiet-Bara A, et al. Magnes Res. 1990;3:31-6 PMID 2397164

Magnesium as a treatment for Pb toxicityRabbits toxed with Pb for 28 days, then treated

for 4 weeksGroup 1 – 40mg/kg magnesium (2.8 gms for 70

kg)Group 2 – 15 mg/kg CaNa2EDTA (therapeutic

dose)Group 3 – contols – no tx.

Soldatovic D, et al. Magnes Res. 1997;10(2):127-33. PubMed PMID: 9368233

Copyright WCrinnion 2013

Urinary Pb levels (umol/L)

Day 0 1 7 13 22 28

Mag 1.62 5.25 6.7 4.54 5.18 3.19

EDTA 2.01 15.0 5.83 1.98 2.67 2.17

Control

1.61 3.96 2.13 1.68 1.88 1.99

Copyright WCrinnion 2013

PMID: 9368233

Pb loss in urine (nmol/L)

Copyright WCrinnion 2013

Days

More resultsMagnesium induced significant decrease in

Zinc protoporphyrin on day 13.Magnesium also lowered ALA better than

CAEDTA

Copyright WCrinnion 2013

PMID: 9368233

Nutrients to Support Heavy Metal DetoxificationN-acetyl-cysteine (200 mg-1800 mg) Protects against lead-induced cytotoxicityNAC along with selenium have been shown to

raise glutathione levels effectively. NAC maintains tissue GSH in face of heavy metal

burdenCombined therapy with DMSA for Pb burden –

“provided more profound efficacy in restoring altered biochem variables and in reducing lead burden…”

Yedjou CG, Tchounwou PB. Int J Environ Res Public Health. 2007 Jun;4(2):132-7 PMID 17617676

Flora SJ, et al. Cell Mol Biol (Noisy-le-grand) 2004;50 Online Pub:OL543-51 PMID 15555419

Pande M, et al. Environ Toxicol Pharmacol 2001;9:173-84 PMID: 11292581

Environmental Health Perspectives Volume 116, Number 1, January 2008

…because NAC is effective at enhancing MeHg excretion when given either orally or intravenously, can decrease brain and fetal levels of MeHg, has minimal side effects, and is widely available in clinical settings, NAC should be evaluated as a potential antidote and biomonitoring agent in humans.

Nutrients to Support Heavy Metal DetoxificationMSM (Methylsulfonylmethane—100 mg)Many hepatic Phase-2 biotransformation

pathways are sulfur dependent. MSM provides a low-cost, well-absorbed sulfur source to facilitate hepatic detoxification.

Nutrients to Support Heavy Metal Detoxification

Alpha Lipoic acid – (100 mg-300 mg) Increases RBC Glutathione levels by 30-70%,

neuroprotective.In addition to being a powerful antioxidant, it

mobilizes As, Pb, Hg, Cd.When used with DMSA it prevents reduction of

GSH in the brain.Pande M, Flora SJS. Toxicology 2002;177:187-96 PMID: 12135622

Does Alpha Lipoic REDUCEmethyl mercury output?

NO!Study on IV application of methyl mercury and

ALA on rats.ALA increased MM excretion into bile by 50-

100% at low doses. Higher doses had a biphasic effect (decr to increase with time)

But, did result in higher brain Hg levels!Gregus Z, et al. Toxicol Appl Pharmacol 1992;114:88-96

PMID: 1585376

Alpha Lipoic AcidAlso effective at ameliorating neural lipid

peroxidation.Animal modelPeroxidation specifically caused by Hg and evident

in cerebral cortex, cerebellum and sciatic nerves.Able to reverse Pb-induced reduction of blood and

brain GSH.Able to reduce brain and kidney Pb levels

Anuradha B, Varalakshmi P. Pharmacol Res 1999;39:67-80 PMID 10051379

Gurer H, et al. Free Rad Biol Med 1999;27:75-81 PMID 10443922

Nutrients to Support Heavy Metal Detoxification

Zinc– (15-45 mg as Zinc Picolinate) Zinc supplementation increases the production

of metallothionein in the body, providing protection for the kidneys from the movement of arsenic, cadmium, and mercury.

Zinc deficiency leads to reduce GSH levelsCo-administration of zinc (10 – 25 mg/kg) and

CaEDTA enhances Pb mobilization.Flora SJS, et al. Pharmacol Toxicol 1994;74:330-333. PMID: 7937565

Nutrients to Support Heavy Metal Detoxification

Selenium– (75-300 mcg. as Selenium Picolinate) Increases glutathione peroxidase levelsSe deficiency lowers GPX levels. Se is antagonistic to Pb, Hg, Al, & Cd in animal

models.

Required component of GSH- PXReduces toxicity of Pb, Cd, Hg

Methionine

Methionine—(150-600 mg)Enhances biliary elimination of lead and help to restore

Pb-induced reduction of GSH.When given with DMPS it reduced liver, kidney and brain cadmium levels better than DMPS alone.

In combination it reduces loss of zinc, copper and iron and restores copper levels

When combined with CaEDTA or DMPS greater Pb excretion occurs

Tandon SK, et al. J Trace Elem Electrolytes Health Dis 1994;8:85-7 PMID 7881280

Nutrients to Support Heavy Metal Detoxification

Copper– (1-4 mg as Copper Picolinate) Can be chelated by DMSA and DMPS

Potassium (3,000 mg from Potassium Citrate)Potassium citrate aids in the renal excretion of

mercury from the body, through alkalinizing the urine.

It is effective by itself and is synergistic when combined with DMSA or DMPS.

Nutrients to Support Heavy Metal Detoxification

Vitamin E– [400-800 IU (mixed complex is more effective than alpha-tocopherol alone]

Membrane stabilizationAntioxidant, crosses BBBPartially prevents CCL4 hepatotoxicity (which is

not lipid peroxide mediated)Pretreatment prevents ozone respiratory damage.Pretreatment decreases adriamycin cardiotoxicityReduced by mercury levels

Botanicals to Support Heavy Metal Detoxification

Uva ursi (75 mg) and Marshmallow (75 mg)—these herbs help protect the kidneys as heavy metals are being eliminated through these organs.

GlutathioneLevels increased by:

IV glutathioneNebulized glutathioneSeleniumNAC and CysteineAscorbic Acid Milk ThistleWhey ProteinAlpha Lipoic Acid

2003

GlutathioneVit E, C and Cysteine have all been shown to

inhibit GSH depletion and lipid peroxidation after endrin exposure.

Oral GSH supplementation in human volunteers failed to show an increase in GSH levels.

Hg and numerous other ubiquitous toxins reduce GSH levels (especially mitochondrial GSH levels).

Additional Help with CleansingReduced L-Glutathione Inhalation by

nebulizer (120 mg 2-3x week) GSH IVs (600 mg-2000 mg)GSH Nasal Spray—1-2 sprays in each nostril

3-4 times daily (60 mg-120 mg)Liposomal GSHOther nutritional IVsAcupunctureMassage/Body workCraniosacral TherapyEnergetic clearing work

Addressing Common Side Effects of Chelating Agents GI upset & nausea from DMSA or DMPS

Peppermint tea, Peppermint tabletsEnteric coated peppermint extract

Caution with preservatives in Normal Saline (benzyl alcohol). Hives or rash along vein of injection site.Rescue Remedy (Bach flowers)Benadryl

Whey Protein Powder Hydrolyzed Lactalbumin—1-2 scoops/day (22.5 g-

45 g) Necessary for proper clearance of chemicals and

metals from the blood. Increases glutathione levels Partial hydrolysis compensates for low HCL and

diminished possible allergy If allergic to Whey, try Soy, Rice or Amino Acid

capsulesHydrolyzing whey protein breaks into smaller,

cysteine and branched-chain amino acids (BCAA), which can help prevent transport of metals across the blood-brain barrier into the brain.

Carbs and Chems and Humans6 subjects fed three different diets for two

weeks eachHigh CHO, High Fat, High Protein

Clearance of antipyrine and theophylline reduced in high CHO and high fat weeks

Clearance of antipyrine and theophylline increased in high protein weeks

Clin Pharmacol Therap 1979;26:493-501

Cruciferous Veggies and Chems10 healthy subjects

Diet known to not induce CYP in animal studiesSubstituted cabbage and brussel sprouts for

veggies in dietAntipyrine T1/2 reduced 13%, clearance

enhanced 11%Phenacetin plasma conc. Reduced 34-67%Clin Pharmacol Therap 1979;25:88-95

Cruciferous veggiesIncreased glucuronic acid conjugates of

phenacetin and antipyrine found.Follow-up study confirmed increased

glucuronidation with cabbage and brussel sprouts.

Protein/CHO ratioIsocalorically increasing P/C ratio enhances

clearance of antipyrine and theophyllineIncreases 2 alpha OH E1 levels and

decreases 16 alpha OH E1Decreases androgen 5 alpha reductionClin Pharmacol Ther 1976;20:643-653J Clin Endocrinol Metab 1984;59:104-107Proc Natl Acad Sci 1983;80:7646-49

The significant association of total calories and dietary fat with blood Pb, independent of other key nutrients, are important findings that, if replicated would further strengthen the recommendation of a low-fat diet as a healthy one for children.

lipophile

hydrophile

Ultrafiltration Tubular secretion

tubular reabsorption

BLOODRENAL ULTRAFILTRATE

URINE (excretion)

Renal Tubules and

Loop of Henle

renal capillary

weak acid tubular reabsorption

to blood in acidic urine lipophilic at low pH e.g. hippuric acid

weak basetubular reabsorption

to blood in alkaline urine e.g. sodium

bicarbonate

AlkalinizationGetting urine pH to >7.5Used medically to treat the following acute

toxicities:Chlorporpamide2,4 – DFlourideMecopropMethotrexateSalicylateEtc.

Proudfoot AT, et al. J Toxicol Clin Toxicol 2004;42(1):1026

Alkaline urineIncreases excretion of mercury

Potassium citrate – 3 gms dailyAssists in clearance of DMSA-complexed cadmium.At pH 5.5 – a significant amount of free CdAt pH 7.4 Cd is “completely chelated” with DMSA

Hibberd AR, et al. J Nutr Env Med 1998;8:219-231

Fang X, et al. Chem Res Toxicol 1996;9(1):284-90 PMID: 8924605

Activated CharcoalEffective at clearing Hg from the intestinal

tract, including the appendix.Used with desferoxamine to prevent GI

absorption of chelated iron.Used for thallium poisoningMcKinney PE. J Toxicol Clin Toxicol 1999;37:103-7 PMID

10078167Gomez HF, et al. Ann Emerg Med 1997;30(5):587-92 PMID

9360566Meggs WJ, et al. J Toxicol Clin Toxicol 1994;32(6):723-30

PMID 7966530

PsylliumNo Recycling of toxins!

Typically 94-97% of bile salts are reabsorbed via enterohepatic recirculation.

Psyllium increases the amount of fecal bile acids by 400% in hamsters (from 6% excretion to 24%)

Cholestryamine only increased it from 6% to 6.6%

Psyllium Necessary to bind toxins in the bowel

preventing hepatic recirculation. Increases activity of CYP7A Increases daily fecal bile concentration

and excretion.Lowers elevated cholesterolLowers elevated blood sugarPrevents gall stone formationIncreases colonic butyrate production

Psyllium and fecal bile acidsRats fed psyllium in their diet had increased

excretion of fecal bile acids3.3% psy. led to increase from 0.5 to 1.5

mmol/day (300% increase)6.67% led to increase to 1.710% led to increase to 2.0

Marlett JA, Fischer MN. J Nutr 2000;130:2137-2142 PMID 12221223

Psyllium and fecal bile acids10 gm daily in six normal subjects

Baseline fecal bile acids = 0.72 mmol/dDuring psyllium use = 0.89 mmol/dPosttest = 0.72 mmol/d

= 23.6% increase in fecal bile acid output

Gelissen IC, et al. Am J Clin Nutr. 1994;59:395-400

PMID 8310991

Rice BranYusho patients given 7-10.5 gm daily

Excretion of dioxins incr. 1.81 and 1.74XYusho patients given RBF and

cholestyramineCombination therapy increased fecal excretion

of PCB, dioxins and furansRBF and cholestryramine

10% RBF incr. PCB excretion 3.4X10% RBF and 5% cholestyramine incr. excr.

5.4XNagayama J, et al. Fukuoka Igaka Zasshi 2005;96:241-8Iida T, et al. Fukuoka Igaka Zasshi 1995;85:226-33Takenaka S, et a. Xenobiotica 1991;21:351-7.

Copyright W Crinnion 2011

Rice Bran and pancreatic lipaseWater extract of defatted rice bran.

Inhibitor of pancreatic lipase4 week trial with mice at 1gm/kg

Suppressed accumulation of visceral fatSuppressed body weight gainNo changes is food consumption, liver or

kidney function

Tsutsumi K, et al. J Agric Food Chem 2000; 48:1653-6

Copyright W Crinnion 2011

Enterohepatic recirculationCompounds ionized at intestinal pH are

more likely to escape this recycling (HCL).

The rate of excretion is a function of the time it takes for the compound to be reabsorbed after excretion. This can be altered by:change in bowel transit timethe rate of hydrolysis by intestinal bacteriathe rate of transport across the cell wall.

Colonic IrrigationsIncrease the clearance of toxic bileLeads to the excretion of lipophylic

chlorinated pesticidesLeads to the excretion of heavy metalsGives tremendous symptomatic improvement

(clinical observation)

Heavy Metals in Colonic Sand

PT ZN AL CU NI PB SN AS CD AN UR THO BE

 1

 625 

 65

 63

 3.1

 2.0

 .96

 .26

 .20

 .13

 .19

 .044

 .015

 2

 22

 23

 6.0

 .31

 2.4

 .15

 .69

 .005

 .34

 .005

 .005

 <dl

 3

 47

 112

 23

 2.7

 1.7

 .17

 .14

 .35

 .018

 .069

 .012

 .007

Thermal Chambers - SaunaIncreases the rate of lipolysis.Xenobiotics in subcutaneous fat pads release

through skin.Xenobiotics from the majority of the fat goes

into circulation.How well can the body handle that?

How well did it handle the toxins before?

Copyright WCrinnion 2008

Heavy metals in sweatCadmium and nickel levels in sweat were higher than

urinary levels.Lead in sweat is associated with dermally absorbed

sources.Lead in sweat may or may not reduce blood lead levels.Daily sweat therapy was used in a single case of Hg

poisoningMercury levels from 76% to 2X that in the urine (ug/L)

Greatest in those who sweated the mostCohn JR. Ann Clin Lab Sci. 1978;8:270-5 PMID: 686643 Lilley SG, et al. Sci Total Environ 1988;76:267-78 PMID: 3238426Omokhodion FO. Sci Total Environ 1991;108:235-42 PMID: 1754878 Omokhodion FO. Sci Total Environ 1991;103:113-22 PMID 1882227Sunderman FW. Ann Clin Lab Sci 1978;8:259-69 PMID 210702Lovejoy HB, et al. J Occup Med 1973;15:590-91 PMID: 4711652

SummaryUse nutrient support during heavy-metal

mobilizationsHave patients on a diet free of heavy metals

and one that will assist the clearance of xenobiotics from the body.

Utilize compounds and techniques that reduce enterohepatic recycling and increase clearance through the fecal and urinary routes.

Utilize thermal chambers