Transcript Nutrients for heavy metals acam webinar 4.2009

Walter J. Crinnion ND
SpiritMed
www.drcrinnion.com
www.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 H2O
 Hydrochloric acid – with meals
 Urine alkalinizing support
 Probiotics
 In 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)
Specific Nutrients
Ascorbic Acid to Support
Heavy Metal Detoxification
Vitamin C – 3,000-12,000mg daily
 Antioxidant
 Reduces 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 Acid
 Enhances CYP function
 Enhances incorporation of Fe into heme
 Prevents nitrosamine formation in GI tract
 Xenobiotics increase AA excretion
 Smoking decreases 40%

One cigarette 55-200 mg
 Sugar 50% decrease
2003
Vitamin C and DMSA
 When 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/kg
 That 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
Magnesium
 40% of CS pts at EHC-Dallas deficient
 Deficiency leads to:
 decreased amounts of CYP450 & NADPH cytochrome
reductase (knocks out Phase 1)
 Decreased levels of GSH
 Decreased ATP production
 Decreased hydroxylation of aniline
 Decreased methylation of aminopyrine
 Supplementation reverses these effects
Mills BJ, et al. Proc Soc Exp Biol Med 1986;181:326-32 PMID: 3945642
Magnesium Deficiency S&S
 Migraines
 Muscle spasm
 Eyestrain
 Constipation
 Muscle weakness
 Arrythmia, PVC
 Fatigue
 Chocolate cravings
 Mild myopathy
 Kidney stones (with B6)
 Myopia
 PMS (with B6 and
 Increased ammonia
potassium)
 Insomnia
 Depression
 Hypertension
Magnesium deficiency
 Cadmium toxicity leads to magnesium deficiency
 Cadmium, lead and mercury may cause or exacerbate
magnesium deficiency, especially for pregnant women
 Certain drugs (xenobiotics) lead to reduced RBC
magnesium levels.
 ROH acts as magnesium diuretic (prevented by Vit E)
 Homeocysteinemia leads to Mag depletion
Kobylec-Zamlynska B, et al. Ginekol Pol 1998;69(12):871-7 PMID 10224744
Semczuk M, Semczuk-Sikora A. Med Sci Monit 2001;7(2):332-4 PMID 11257745
Steidl L, et al. Magnesium 1987;6:284-95 PMID 3129621
Rivlin RS. J Am Coll Nutr 1994;13(5):416-23 PMID 7836619
Li W, et al. Neurosci Lett 1999;274:83-6 PMID 10553943
Magnesium supplementation
 Supplementation with magnesium and B6 resulted in
decreased RBC levels (increased excretion) of
cadmium and lead
 64 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 15724866
Kedzierska E. Ann Acad Med Stetin 2003;49:131-43 PMID 15552844
Mills BJ, et al. Proc Soc Exp Biol Med 1986;181:326-32 PMID 3945642
Guiet-Bara A, et al. Magnes Res. 1990;3:31-6 PMID 2397164
Magnesium as a treatment for
Pb toxicity
 Rabbits toxed with Pb for 28 days, then treated for 4
weeks
 Group 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
PMID: 9368233
Copyright WCrinnion 2013
Pb loss in urine (nmol/L)
Days
Copyright WCrinnion 2013
More results
 Magnesium induced significant decrease in Zinc
protoporphyrin on day 13.
 Magnesium also lowered ALA better than CAEDTA
PMID: 9368233
Copyright WCrinnion 2013
Nutrients to Support
Heavy Metal Detoxification
N-acetyl-cysteine (200 mg-1800 mg)
 Protects against lead-induced cytotoxicity
 NAC along with selenium have been shown to raise
glutathione levels effectively.
 NAC maintains tissue GSH in face of heavy metal
burden
 Combined 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
…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.
Environmental Health Perspectives Volume 116, Number 1, January 2008
Nutrients to Support
Heavy Metal Detoxification
MSM (Methylsulfonylmethane—100 mg)
 Many hepatic Phase-2 biotransformation pathways are
sulfur dependent. MSM provides a low-cost, wellabsorbed 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 REDUCE
methyl 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 Acid
 Also effective at ameliorating neural lipid
peroxidation.
 Animal model
 Peroxidation 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 levels
Co-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 levels
Se deficiency lowers GPX levels.
Se is antagonistic to Pb, Hg, Al, & Cd in animal models.
Required component of GSH- PX
 Reduces 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 stabilization
 Antioxidant, crosses BBB
 Partially prevents CCL4 hepatotoxicity (which is not lipid
peroxide mediated)
 Pretreatment prevents ozone respiratory damage.
 Pretreatment decreases adriamycin cardiotoxicity
 Reduced 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.
Glutathione
 Levels increased by:
 IV glutathione
 Nebulized glutathione
 Selenium
 NAC and Cysteine
 Ascorbic Acid
 Milk Thistle
 Whey Protein
 Alpha Lipoic Acid
2003
Glutathione
 Vit 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 Cleansing
 Reduced 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 GSH
 Other nutritional IVs
 Acupuncture
 Massage/Body work
 Craniosacral Therapy
 Energetic clearing work
Addressing Common Side Effects of Chelating Agents
 GI upset & nausea from DMSA or DMPS
 Peppermint tea, Peppermint tablets
 Enteric 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 capsules
Hydrolyzing 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.
Dietary assistance
Macro-view of diets
Carbs and Chems and Humans
 6 subjects fed three different diets for two weeks each
 High 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 Chems
 10 healthy subjects
 Diet known to not induce CYP in animal studies
 Substituted cabbage and brussel sprouts for veggies in
diet
 Antipyrine T1/2 reduced 13%, clearance enhanced 11%
 Phenacetin plasma conc. Reduced 34-67%
Clin Pharmacol Therap 1979;25:88-95
Cruciferous veggies
 Increased glucuronic acid conjugates of phenacetin
and antipyrine found.
 Follow-up study confirmed increased glucuronidation
with cabbage and brussel sprouts.
Protein/CHO ratio
 Isocalorically increasing P/C ratio enhances clearance
of antipyrine and theophylline
 Increases 2 alpha OH E1 levels and decreases 16 alpha
OH E1
 Decreases androgen 5 alpha reduction
Clin Pharmacol Ther 1976;20:643-653
J Clin Endocrinol Metab 1984;59:104-107
Proc 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.
Helping the heavy metals leave
through urine and bile
Renal Ultrafiltration and Selective
Tubular Reabsorption
Ultrafiltration
Tubular secretion
RENAL ULTRAFILTRATE
Renal Tubules
and
Loop of Henle
BLOOD
tubular
reabsorption
lipophile
hydrophile
URINE (excretion)
renal
capillary
Urinary pH & Tubular Reabsorption
 weak acid
 tubular reabsorption to
blood in acidic urine


lipophilic at low pH
e.g. hippuric acid
 weak base
 tubular reabsorption to
blood in alkaline urine

e.g. sodium bicarbonate
Alkalinization
 Getting urine pH to >7.5
 Used medically to treat the following acute toxicities:
 Chlorporpamide
 2,4 – D
 Flouride
 Mecoprop
 Methotrexate
 Salicylate
 Etc.
Proudfoot AT, et al. J Toxicol Clin Toxicol 2004;42(1):1026
Alkaline urine
 Increases excretion of mercury
 Potassium citrate – 3 gms daily
 Assists in clearance of DMSA-complexed cadmium.
 At pH 5.5 – a significant amount of free Cd
 At 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 Charcoal
 Effective at clearing Hg from the intestinal tract,
including the appendix.
 Used with desferoxamine to prevent GI absorption of
chelated iron.
 Used for thallium poisoning
McKinney PE. J Toxicol Clin Toxicol 1999;37:103-7 PMID 10078167
Gomez HF, et al. Ann Emerg Med 1997;30(5):587-92 PMID 9360566
Meggs WJ, et al. J Toxicol Clin Toxicol 1994;32(6):723-30 PMID 7966530
Psyllium
No 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 cholesterol
Lowers elevated blood sugar
Prevents gall stone formation
Increases colonic butyrate production
Psyllium and fecal bile acids
Rats fed psyllium in their diet had increased excretion of
fecal bile acids
 3.3% psy. led to increase from 0.5 to 1.5 mmol/day (300%
increase)
 6.67% led to increase to 1.7
 10% led to increase to 2.0
Marlett JA, Fischer MN. J Nutr 2000;130:2137-2142 PMID 12221223
Psyllium and fecal bile acids
 10 gm daily in six normal subjects
 Baseline fecal bile acids = 0.72 mmol/d
 During psyllium use
= 0.89 mmol/d
 Posttest
= 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 Bran
 Yusho patients given 7-10.5 gm daily
 Excretion of dioxins incr. 1.81 and 1.74X
 Yusho patients given RBF and cholestyramine
 Combination therapy increased fecal excretion of PCB,
dioxins and furans
 RBF and cholestryramine
 10% RBF incr. PCB excretion 3.4X
 10% RBF and 5% cholestyramine incr. excr. 5.4X
Nagayama J, et al. Fukuoka Igaka Zasshi 2005;96:241-8
Iida T, et al. Fukuoka Igaka Zasshi 1995;85:226-33
Takenaka S, et a. Xenobiotica 1991;21:351-7.
Copyright W Crinnion 2011
Rice Bran and pancreatic lipase
 Water extract of defatted rice bran.
 Inhibitor of pancreatic lipase
 4 week trial with mice at 1gm/kg
 Suppressed accumulation of visceral fat
 Suppressed body weight gain
 No 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 recirculation
 Compounds 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 time
 the rate of hydrolysis by intestinal bacteria
 the rate of transport across the cell wall.
Colonic Irrigations
 Increase the clearance of toxic bile
 Leads to the excretion of lipophylic chlorinated
pesticides
 Leads to the excretion of heavy metals
 Gives 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 - Sauna
 Increases 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?
Heavy metals in sweat
 Cadmium 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
poisoning
Mercury levels from 76% to 2X that in the urine (ug/L)
 Greatest in those who sweated the most
Cohn JR. Ann Clin Lab Sci. 1978;8:270-5 PMID: 686643
Lilley SG, et al. Sci Total Environ 1988;76:267-78 PMID: 3238426
Omokhodion FO. Sci Total Environ 1991;108:235-42 PMID: 1754878
Omokhodion FO. Sci Total Environ 1991;103:113-22 PMID 1882227
Sunderman FW. Ann Clin Lab Sci 1978;8:259-69 PMID 210702
Lovejoy HB, et al. J Occup Med 1973;15:590-91 PMID: 4711652
Copyright WCrinnion 2008
Summary
 Use nutrient support during heavy-metal
mobilizations
 Have 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