NMDF121 SN23 Lecture Toxins...• Nuts, legumes, grains and chocolate higher levels • Fruits and vegetables intermediate content • Fish, milk, eggs lower content • Used in industry

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NMDF121

Session 23

Toxic Metals

Naturopathic Medicine Department


Topic Summary

• Toxic Metals

– Qualities and categories

• Arsenic

• Cadmium

• Mercury

• Nickel

• Aluminium


Toxic Metals

• Not usually consumed by or found in humans

• Difficult to excrete from the system

• Interfere with body function

• Categories:

• Sources of contamination

• Methods of toxicity

• Symptoms of toxicity

• High risk populations

• Treatment of toxicity

• Prevention


Arsenic

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ch&redirs=0&search=arsenic&fulltext=Search&ns0=1&ns6=1&ns1

2=1&ns14=1

http://upload.wikimedia.org/wikipedia/commons/f/f5/Arsenic_acid.svg

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http://upload.wikimedia.org/wikipedia/commons/a/a7/Arsenic_trioxide.jpg

http://upload.wikimedia.org/wikipedia/commons/a/a7/Arsenic_trioxide.jpg


Arsenic

• Aside from conjuring images of toxicity, evidence is accumulating that arsenic is an essential element

• Appears to facilitate use of methyl groups such as SAMe

• Regulates cellular signal transduction pathways including insulin

• Through activation of the G-protein-coupled receptor S1P1, influences cell proliferation and differentiation

(Gropper and Smith 2013)


Sources

• Content depends on soil & pollution

• Weed killers

• Environmental toxin from burning fuel oils and coals

• Small amounts in food such as meats, grains and dairy

• Higher in filtering mollusks, fish and Hijiki seaweed

• Most toxic: inorganic arsenite, trivalent organoarsenicals.

• Less toxic: organic forms, pentavalent, methylated arsenic

compounds

(Agency for Toxic Substances and Disease Registry 2007)

(Food Standards Australia, 2013)


Arsenic

• Metabolism:

• Organic - little or none in liver

• Inorganic - reduced, methylated or both in liver

• Concentrates in skin, hair, nails

• Excreted mostly via kidneys in urine

• Derivative arsenic trioxide approved treatment of acute promyelocytic leukemia• Exhibits potent antitumor activity

• Promoted complete remission in over 50% of patients

• Has side effects on heart and blood cells(Nicolis 2009)


Deficiency

• Recommended intake

• Suggested: 12-25 µg

• No tolerable upper limit established(Gropper et al, 2009)

• Deficiency in animals –

– Impairs methionine metabolism

– Decreased SAMe decarboxylase activity

– Decreased taurine production(Uthus 1993)


Toxicity

• Methods of toxicity:

• May displace phosphorous and phosphates in some

reactions in the body

• Antagonises selenium and iodine (Gropper 2013)

• Symptoms of toxicity:

• Possibly – hair loss, dermatitis, diarrhoea, fatigue,

headaches, confusion, muscle pains, red and white

blood cell problems, neurologic symptoms, and liver

and kidney damage.(Agency for Toxic Substances and Disease Registry 2007)


Arsenic

• Amounts:

• 7-10ppm in hair analysis

• High risk population:

• Miners, smelters and vineyard workers

• Treatment:

• Dimercaprol (given 24 hours after exposure)

• Can be supported with Vitamin C

• Prevention:

• Avoid sources


Cadmium

http://commons.wikimedia.org/wiki/

File:Cadmium_nitrate.png

http://upload.wikimedia.org/wikipedia/commons/a/a2/Cadmium_nitrate.png

http://upload.wikimedia.org/wikipedia/commons/a/a2/Cadmium_nitrate.png


Sources

• Cigarette smoke – 1 mcg/cigarette, 70% exhaled

• Refined foods and root vegetables

• Water pipes - galvanised

• Coal burning

• Shellfish, sea weeds

• Ceramics, dental materials, storage batteries


Methods of Toxicity

• Competes with zinc for binding sites disrupting normal function

• May catalyse oxidation reactions

• Symptoms:• Kidney damage

• Cardiac hypertrophy

• Progressive atherosclerosis

• Depressed immunity

• Prostate enlargement

• Bone deformities

• Emphysema

• Anaemia


Cadmium

• Amounts leading to toxicity:

• Increased absorption with zinc, iron, or calcium

deficiency

• 2ppm in hair analysis

(Bernhoft 2013)


• Industrial and metal workers, zinc miners, smokers

and passive smokers, diets with refined flours and

sugars (white rice)


Cadmium

• Treatment:

• EDTA chelation

• High intake of zinc and selenium will prevent further

absorption

• Iron, copper, selenium and Vitamin C will help

elimination

• Prevention

• Minimise exposure

• Ensure adequate zinc levels (15-30mg/day)

• Strengthen kidney function


Review Questions

1. List common sources of arsenic and cadmium.

2. What are the main functions thought to be

associated with arsenic?

3. Which mineral does cadmium mimic on enzyme

binding sites? Why is this an issue?


Lead

http://commons.wikimedia.org/wiki/File:Lead.jpg

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Sources

• Batteries

• Solder

• Pottery

• Pigments - cosmetics

• Gasoline

• Paint

• Food – grown near industrial areas


Methods and Symptoms of Toxicity

• Interferes with calcium, iron, copper, and zinc

• Inactivates metalloenzymes in brain chemistry

• Can react with cell membranes

• Immunosuppressant

• May have some affect on gastrointestinal function


• Acute – headache, fatigue, muscle pains, anorexia, constipation,

vomiting, pallor, anaemia.

• Low level – affects intelligence, attention span, language and

memory. Insomnia and nightmares, hyperactivity and retardation,

and senility




Lead

• Amounts:

• 0-30ppm may be normal.


• Anyone working directly with lead or those working in zinc or

vanadium mining.

• Children and pregnant women.

• Treatment:

• EDTA

• Calcium and vitamin D and C supplementation

• Cysteine and methionine – 250mg twice daily


Lead

• Prevention:

• Renovation of old houses with lead-based paint

• Do not store food in pottery

• Avoid soldered cans

• Evaluate for lead levels any questionable substances (i.e.

water)

• High amounts of lead has been linked to decreases in

cognitive performance.


Mercury

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http://upload.wikimedia.org/wikipedia/commons/c/c0/Bille-Hg.jpg

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Sources

• Fungicides and pesticides

• Cosmetics – antibacterial additive

• Dental fillings

• Medicines

• Coal burning

• Fish


Methods and Symptoms of Toxicity

• Affects the inherent protein structure via damage to cell membranes and inactivation of enzymes

• Immunodepressant

• May interfere with selenium


• Inhalation – Fever, chills, coughing, and chest pain

• Ingestion – fatigue, insomnia, irritability, anorexia, loss of

sex drive, headache, forgetfulness or poor memory.

Dizziness, tremors, uncoordination, and depression.

• Possible relationship with multiple sclerosis (small trial).

(Attar 2012)


Mercury

• Amounts leading to toxicity:

• >5ppm hair levels


• Farmers and those with amalgam fillings

• Treatment:

• Drinking milk – mercury acts on protein in milk

• Vitamin C, selenium, pectin and alginates

• Prevention:

• High fibre diet

• Selenium 100-200mcg


Mercury• FSANZ advice regarding Mercury:Pregnant women and women

planning pregnancy

1 serve equals 150 grams#

Children (up to 6 years)

1 serve equals 75 grams #

Rest of the population

1 serve equals 150 grams #

2 – 3 serves per week of any fish and seafood not listed below 2 – 3 serves per week of any fish and seafood

not listed in the column below

OR

1 serve per week of Orange Roughy (Sea Perch) or Catfish and no other

fish that week

1 serve per week of Shark (Flake) or Billfish

(Swordfish / Broadbill and Marlin) and no other

fish that week

OR

1 serve per fortnight of Shark (Flake) or Billfish (Swordfish / Broadbill and

Marlin) and no other fish that fortnight

# A 150 gram serve for adults and older children is equivalent to approximately two frozen crumbed fish portions.

A 75 gram serve for children is approximately three fish fingers (Hake or Hoki is used in fish fingers).

Canned fish is sold in various sizes; for example, the snack- size cans of tuna are approximately 95 grams.

If you are in doubt about the type of fish or boneless fish fillets you are buying, ask the retailer and confirm the name of the

fish being supplied. This also applies when eating out.

http://www.foodstandards.gov.au/consumer/chemicals/mercur

y/Pages/default.aspx


Review Questions

1. List the main sources of mercury and lead.

2. What are the main minerals thought to be affected

by lead? Which system has this been noted to

mostly affect?

3. What is the main mineral known to be affected by

mercury? Which endogenously produced

antioxidant compound is dependent on this

mineral?


Activity

o Read the following journal article:

Wright, R. O., & Baccarelli, A. (2007). Metals and neurotoxicology. The

Journal Of Nutrition, 137(12), 2809-2813.

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.com/login.aspx?direct=true&db=mdc&AN=18029504&site=eds-

live&scope=site

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Activity (continued)

o Make a dot point summary of the most important factors

under each of the following headings –

• Neurotoxicity of iron and manganese

• Neurotoxicity of arsenic and cadmium

• Neurotoxicity of zinc and copper

• Metal mixtures and neurodevelopment

o Discuss these points in small groups then present a

summary from your group to the class

o Online students discuss in the online forums


Nickel

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el.jpg

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Sources

• Plant sources contain higher levels than animal

foods

• Nuts, legumes, grains and chocolate higher levels

• Fruits and vegetables intermediate content

• Fish, milk, eggs lower content

• Used in industry for stainless steel and nickel-

cadmium batteries

• Released into environment when burned(Gropper 2013)


Function

o The specific function of nickel in humans in not known.

o Some functions that require more research are:

• May be involved with folate and B12 in the metabolism of methionine

• This mineral is also a co-factor of various enzymes and may substitute other minerals such as Cu, Zn and Fe, typically negatively impacting enzyme function

• Enhances activity and stability in the complement system when replacing Mg in the formation of C3 convertase enzyme

(Gropper, 2013)


Toxicity

• Intense pulmonary and gastrointestinal toxicity.

• Diffuse interstitial pneumonitis.

• Cerebral oedema.

• Antagonises Fe absorption

(Kohlmeier, 2003; Oseicki, 2002)


Deficiency

• In animals –

• Decreased reproduction

• Depressed growth

• Altered Fe, lipid and CHO metabolism

• Impaired haematopoiesis, probably due to altered iron

metabolism

• Effects on bone and thyroid hormone metabolism

• Daily dosage – 100-260mcg

• Toxic dose - >60mg per day(Kohlmeier, 2003; Gropper 2013)


Aluminium

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le:Aluminium_hydroxide.svg

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Sources• Foods

• Food additives – AlPO4 in processed cheese, Potassium

Alum to whiten flour, Sodium silicoaluminate for free-

flowing salt

• Medicines

• Antacids – Aluminum hydroxide

• Cosmetics

• Cookware – leaching from pots, pans and foil

• Especially with acid foods (tomatoes, rhubarb)

• Increased if cooking with fluoridated water


Methods of Toxicity

• May interfere with some magnesium functions

• May reduce vitamin levels or bind to DNA

• Associated with weakened gastrointestinal tissue

• Bind pepsin

• Astringent

• May block underarm lymphatics


Toxicity

• Symptoms:

• Acute – constipation, nausea, anorexia, colic, gastrointestinal irritation, skin problems

• Chronic – muscle twitching, numbness, paralysis, fatty degeneration of kidney and liver

• Hypothesised link to Alzheimer’s and Parkinson’s disease

• Hyperactivity and learning disorders in children

• Amounts:

• Best measured by hair analysis


Aluminum

• High Risk Population:

• Diets high in refined foods, flours, baked goods, processed cheeses and common table salt

• Those using antacids, antiperspirants or cook with aluminum foil or kitchenware

• Treatment:

• Use chelation therapy (EDTA, desferrioxamine)

• Support with Calcium, Magnesium and zinc


Aluminum - Research

Aluminium in Over-the-Counter Drugs Risks Outweigh

Benefits?

Over-the-counter antacids are the most important source for human

aluminium exposure from a quantitative point of view. However,

aluminium can act as a powerful neurological toxicant and provoke

embryonic and foetal toxic effects in animals and humans after

gestational exposure. Despite these facts, the patient information

leaflets from antacids that are available OTC show substantial

differences regarding warnings. It seems advisable that all patients

should receive the same information on aluminium toxicity from patient

information leaflets, in particular with regard to the increased

absorption through concomitant administration with citrate-containing

beverages and the use of such antacids during pregnancy.

(Reinke 2003)


Review Questions

1. List common sources of nickel and aluminium.

2. What are the main functions thought to be

associated with nickel?

3. Which mineral is aluminium thought to interfere

with?


References

• Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for

Arsenic (Update). U.S. Public Health Service, U.S. Department of Health and Human

Services, Atlanta, GA. 2007.

• Gropper and Smith 2013. Advanced Nutrition and Human Metabolism 6th Ed.

Wadsworth Cengage Learning, USA.

• Kakela, R., Kakela, A. and Hyvarinen, H. (1999) Effects of nickel chloride on

reproduction of the rat and possible antagonistic role of selenium, Comparative

Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology,

123, 27-37.

• Lowe, J. F. and Frazee, L. A. (2006) Update on Prostate Cancer Chemoprevention,

Pharmacotherapy, 26, 353-359.

• Nicolis et al 2009. Arsenite medicinal use, metabolism, pharmacokinetics and

monitoring in human hair. Biochemie.91: 1260-67

• Reinke et al. 2003. Aluminium in over-the-counter drugs: risks outweigh benefits?

Drug Saf. 26: 14; 1011-25

• Uthus and Nielsen 1993. Determination of the possible reuqirements and reference

dose level for arsenic in humans. Scand J Work Environ Health 19 (suppl 1) 137-38


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Documents

NMDF121 SN23 Lecture Toxins...• Nuts, legumes, grains and chocolate higher levels • Fruits and vegetables intermediate content • Fish, milk, eggs lower content • Used in industry