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- Dr Alan Stewart MRCP
- www.stewartnutrition.co.uk
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- Supplements of vitamins, minerals and other nutrients are taken by 40%
of UK adults
- Studies involving high dose supplements or their prolonged use have
revealed adverse effects
- The risks of supplement use need to be more well known
- Practitioners and the supplement industry need to address the issue of
supplement safety
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- Safety is central to FSA, DEFRA, EFSA & DoH policies
Food Standards Agency is responsible for food supplements
- Professional and Authorizing Bodies
Training of nutritionists is overseen by the National Occupation
Standards, Nutritional Therapy Council and
British Association for Applied Nutrition & Nutritional
Therapy who set standards for training and practice
- UK Supplement Industry – formulation, manufacture & marketing
Health Food Manufacturers’ Association www.hfma.co.uk
“ To promote high standards of product manufacture and
presentation to ensure consumer
safety..”
- Council for Responsible Nutrition UK www.crn.org.uk
“members all agree to abide by voluntary quality standards to
ensure consumer safety and confidence.”
- Medicines Health Regulatory Authority
Accepts reports of adverse reactions to nutritional supplements
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- National Occupation Standards for Nutritional Therapy
CNH8. Knowledge and Understanding
- “16. ways in which individual safety may be compromised by
inappropriate treatment and how to minimise such risks “
https://tools.skillsforhealth.org.uk/competence/show/html/id/2805/
- Nutritional Therapy Council
Core Curriculum for accredited nutrition courses.
- 2.1.3 Micronutrients (L 3-7)
“4. Explain the signs and symptoms associated with micronutrient/
orthomolecular compound deficiency, imbalance and toxicity.”
2.2.2 Treatment and Scope of Methods of Nutritional Therapy
“ 3. Discuss the purpose, range and limitations of different
methods of nutritional therapy”
- British Association for Applied Nutrition & Nutritional Therapy
Mission statement.
- “2. Promote high standards of education, training, practice and
integrity in the nutrition profession”
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- Dietary Reference Values:
- Dept of Health 1991
- LRNI “An amount enough for only the few people in a group who have low
needs”
- EAR “About half will usually need more than the EAR and half less”
- RNI “An amount of the nutrient that is enough, or more than enough, for
about 97% of people in a group”
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- EAR Estimated Average Requirement
- RNI Recommended Nutrient Intake
- LRNI Lower Reference Nutrient Intake an amount enough for only a small %
of population
- UL Tolerable Upper Intake Level at which no evidence of toxicity is
demonstrable
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- “All things are poison and nothing is without poison: only the dose
makes a thing a poison.”
- “Alle Dinge sind Gift und nichts ist ohne Gift: allein die Dosis macht,
das ein Ding kein Gift ist.”
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- Supplement categories are reported with slight differences between
surveys
- Females are usually bigger consumers of supplements than males
- Most iron and multivitamins with iron are consumed equally by females
and males
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10
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- State of Adequacy
- State of Negative Balance:
1. Poor Intake
2. Reduced absorption
3. Increased losses
4. Increased requirement
5. Altered metabolism – illness, alcohol, drugs, toxins,
genetics
- Decline in Tissue Stores
- Loss of Function:
1. Symptoms
2. Physical Signs
3. Organ Failure
- Death
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- State of Adequacy
- State of Negative Balance:
1. Poor Intake
2. Reduced absorption
3. Increased losses
4. Increased requirement
5. Altered metabolism
illness, alcohol, drugs,
genetics
- Decline in Tissue Stores
- Loss of Function:
1. Symptoms
2. Physical Signs
3. Organ Failure
- Death
- State of Adequacy
- State of Positive Balance:
1. Increased Intake
2. Increased absorption
3. Reduced losses
4. Reduced requirement
5. Altered metabolism
illness, alcohol,
drugs, genetics
increased sensitivity
to nutrient
- Increase in Tissue Stores
- Loss of Function:
1. Symptoms
2. Physical Signs
3. Organ Failure
- Death
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- Possible Adverse Effects
Expert reports, data from trials, case reports
US Supplements Label Database
- Dose-Response Effect
Data mainly from trials and epidemiological data
- Exposure Assessment
Sources – food, supplements, water, industrial etc..
UK National Diet and Nutrition Surveys,
UK Committee on Toxicity – intakes from all sources
- Modifying Factors
Age, smoking, asbestos, alcohol, disease of excretory organs –
liver and kidney, drugs, genetic factors etc…
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- Safe Upper Levels for Vitamins and Minerals May 2003
Expert Group on Vitamins and Minerals, FSA
Safe Upper Levels and Guidance Levels
www.food.gov.uk/multimedia/pdfs/vitmin2003.pdf
- Review of Dietary Advice on Vitamin A Sept 2005
Scientific Advisory Committee on Nutrition
http://www.sacn.gov.uk/pdfs/sacn_vita_report.pdf
http://www.sacn.gov.uk/pdfs/Vitamin_A_Report_and_Annexes.pdf
- Tolerable Upper Intake Levels for Vitamins and Minerals Feb 2006
Scientific Committee on Food, European Food Safety
Authority
http://europa.eu.int/comm/food/fc/sc/scf/index_en.html
- Mortality in Randomized Trials of Antioxidant
Supplements for Primary and Secondary Prevention Mar 2007
Bjelakovic G et al JAMA.2007;297:842-857
www.cochrane.org/reviews/en/ab007176.html
- Dietary Reference Intakes (and ULs) Book 2006
(+ Tolerable Upper Intake Levels) Otten JJ et al Institute of
Medicine
http://www.nap.edu/catalog/11537.html
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- Safe Upper Levels, SULs 8
derived from human data
- Guidance Levels, GLs 22
- derived from animal/incomplete human data
- Based on a 60 kg female
- “ ..are the doses of vitamins and minerals that susceptible individuals
could take daily on a life-long basis, without medical supervision.”
- Total Safe Intakes
= food + water + supplements
for retinol and some trace elements
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- Tolerable Upper = NOAEL/LOAEL
- Intake Level (UL) Uncertainty Factor, UF
- Uncertainty Factors selected by
Institute of Medicine
- Manganese = 1
- Vitamin D = 1.2
- Vitamin A and Zinc = 1.5
- Selenium and vitamin B6 = 2
- Folic acid = 5
- Vitamin E = 36
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- UK Safe Upper Levels (SULs) Guidance Levels (GLs) “are the doses of
vitamins and minerals that susceptible individuals could take daily on a
life-long basis, without medical supervision.”
Single figure, applies to adults only, based on 60 kg
female
Total Safe Intakes (TSIs) are set for retinol and some trace
elements
- US Tolerable Upper Intake Levels (ULs)
Range of figures depending upon age and sex
“is the highest average daily nutrient intake level likely to
pose no risk of adverse effects for nearly all people in a particular
group”
Based on total intake from food, water and supplements
- EU Tolerable Upper Intake Level (UL)
“the maximum level of total chronic daily intake of a nutrient
(from all sources) judged to be unlikely to pose a risk of adverse
effects”.
ULs vary with age and sex and exclude “those under medical
supervision and certain disease states” but includes “sensitive
individuals”
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- Acute Toxicity
Minor – gastrointestinal upset – Mg, Fe, Zn,
Severe – large amounts of vitamins A, D, C
- Chronic Toxicity
Osteoporosis – vitamin A
Nervous system – vitamin B6, Mn, Cu
Liver disease – Fe, Cu, vitamin A, beta-carotene
Metabolic Effects – hypercalcaemia, renal stones, induced
deficiency
- Cancer
Induction – antioxidants may act as pro-oxidant
Growth Rate – zinc,
vitamins A and B
- Adverse Pregnancy Effects
Fetal development/growth – Fe, vitamins A, C and E
- Minor and Idiosyncratic Adverse Effects
Dermatological – beta-carotene, vitamin B12, n-3 EFAs and others
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- Food and Beverages
All nutrients
- Fortified Foods
Vits A, D, E, C, B group, Ca, Fe and a few trace elements
- Supplements
All nutrients
- Water
Mains supply – Ca, Mg, Cu, Bottled – Mg, Na
Non-mains supply – Ca, Mg, Cu, Fe and Mn
- Air and Industrial Exposure
Mn (60,000 with exposure in UK – HSE estimate)
Other trace elements
- Drugs and Other
Iodine (disinfectants, amiodarone, thyroxine)
Ca/Mg (antacids), Cu (bracelet), Zn (dental fixative)
Retinol (dermatological preparations), vit K (mouth wash)
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- Four surveys covering ages 1.5 yrs to >85 yrs
- Random samples of the British population with approximately 2,000
subjects in each. The very ill,
pregnant women and those of no fixed abode were not included
- Field-work conducted between 1990 and 2001
- Collected information on:
- 4-7 day weighed dietary intakes
- supplement and drug use
- laboratory measures of nutrient status
- alcohol intake and smoking
- tests of liver and kidney function (elderly only)
- BP and BMI
- The surveys provide detailed information about the prevalence of
nutritional deficiencies and excess and some of the associated risk
factors
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- The above are the nutrients most likely to be associated with a variety
of adverse effects. No intake data on selenium
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- Supplement categories are reported with slight differences between
surveys
- Females are usually bigger consumers of supplements than males
- Most iron and multivitamins with iron are consumed equally by females
and males
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- Total Safe Intake, TSI
1500 ug/day
- UK adult diet provides on average 700 ug/day
- Supplements should usually be limited to 800 ug/day
none in pregnancy
- % population intakes >TSI
- adults (19-64yrs) M 9%,
F 4%
- elderly (65+ yrs) M
11%, F10%
- High intakes can occur from:
- food – liver, very high dairy
- supplements multivitamins
and cod liver oil
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- Acute Toxicity: – rare >50,000ug/day
- liver failure, death
- Chronic Toxicity:
- pregnancy (limb deformity)
- osteoporosis
- hair loss, dry skin
- hypercalcaemia
- Recommendations to:
- Farming Industry
- Food Supplement Industry
- Supplement Industry:
- overages of <30-65%
according to CRN/HFMA
- only 50% of cooperated in a
subsequent survey
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- Cod Liver Oil 10 mls
1,800ug
- Holford Multivitamin
1,200ug
- HealthSpan Multi 50+ 1,000
ug
- H and B ABC Plus Senior 1,050
ug
- Solgar Solovit 750 ug
- Biocare Adult Multi Vit+Mins 600
ug
- Continental Multivitamins None
- Solgar Multivitamins – many None
- Seven Seas Premium CLO None
- CLO in Norway reduced by 70%
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- Nurses’ Health Study in the USA
- 72,337 predominantly white post-menopausal women 18 yr follow-up
- High intakes of retinol >2000 ug/day vs <500 ug/day;
fracture RR 1.89; 95% CI 1.33 to 2.68
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- 2799 women age 50 -74 years in the US
- No linear relationship between serum retinol and risk of hip fracture
- Fracture risk was increased in the:
lowest quintile – HR 1.9
(95% CI:1.1-3.3)
highest quintile – HR 2.1 (95% CI:1.2-3.6)
- Both low and high serum retinol may be associated with an increased risk
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- Prospective study of 2606 British women median age 75 years followed up
for a median duration of 3.7 years
- Subjects were part of a bisphosphonate trial
- 312 incident osteoporotic fractures and 92 incident hip fractures
- The risk of osteoporotic fracture was slightly less in the highest
quartile of serum retinol
- Multivitamin or cod liver oil use was associated with a significantly
lower risk of any fracture
- “We suggest that there is not sufficient evidence to support the
elimination of retinol supplements or restriction of dietary intake of
pre-formed retinol or beta-carotene on the basis of skeletal risk”
- However, this was not a representative survey ……
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- Subject exclusion criteria:
hypocalcaemia
neutropenia
abnormal LFTs
renal impairment
- Serum retinol and 25(OH)D correlated r = 0.12, p <0.001
- * Weight difference
cases vs controls (p
<0.01)
- Conclusion:
CLO/Multivitamins are safe in elderly women
if – none of the above
and not overweight/obese i.e. non-normal population
- However many will have an increased risk as they age
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- Abnormal LFTs may occur in 10% - 30% of UK adults
- Common causes:
- Alcohol excess
- Obesity - NAFLD
- Hepatitis B and C
- Drug-induced
- Auto-immune liver disease
- Elevated Alkaline Phosphatase -
cholestatic liver disease
- increased mortality
- Elevated Gamma GT
- usually alcohol excess
- Abnormal LFTS
- potential accumulation Mn, Cu
- altered vitamin A status
- reduced 25(OH) vit.D
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- Reduced Hepatic Content in Liver Disease
Leo and Lieber. NEJM 1982;307:597-601
- Elevated Plasma Retinol with high Alcohol Intake
20% increase in plasma DNSBA
1989
- Supplements Increase Plasma (Liver) Alkaline Phosphatase
Use of 7,576 ug/day for 3.8 yrs was associated with a 7%
increase
Cartmel B et al AJCN 1999;69:937-43
- Liver Damage with High Doses >15,000 ug/day
Sheth A et al J Am Diet Assoc 2008;108(9) 1536-7
- Hepatitis C - Poorer Response to Interferon in those with high total
intake of retinol
Loguerico C et al Am J Gastro. 2008;103(12) 3159-3166
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- Retinol Binding Protein transports retinol and thyroxine
- Produced by the liver, choroid plexus and adipose tissue
- RBP4 is produced by adipocytes and is the main carrier protein for
retinol in serum
- Elevated RBP4 is associated with abdominal obesity, raised TG levels,
decreased HDL levels and systolic hypertension
- Serum RBP4 correlates with insulin resistance in obese and pre-diabetic
subjects
- Serum RBP4 and serum retinol levels are moderately correlated
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- The response of patients with HCV-hepatitis to standard treatment is
~60%
- The response is significantly better in younger people, with early
disease, who are not obese, drink less alcohol and differs with the
viral genotype
- The patient’s diet may also be a factor
- Intake of some micronutrients may increase and others reduce the chance
of successful outcome to therapy
- Because multiple statistical analyses were made no firm conclusions
about micronutrient intake and disease progression can (yet) be made
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- 1084 with HCV-related chronic hepatitis in Southern Italy 24-48 wk trial
- Patients with HIV, HBV-hepatitis or other major illness were excluded
- 432 Treated with interferon + ribavarin. 246 responded; 186 didn’t
respond
- Non-responders were likely to be >50 yrs, BMI >25 kg/m2 and
alcohol ++
- 7-day diet diaries were used to calculate nutrient intake
- Intakes were also compared with 2,326 healthy blood-donor controls
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- The OC Pill and HRT
These cause a small, probably insignificant, rise in serum
retinol
- Pregnancy and Lactation Requirement Increases
The Reference Nutrient Intake, rises from 600 ug/day to 700 ug
and in lactation to 950 ug/day. A
diet rich in dairy foods and vegetables should be emphasised
- Retinol is needed for growth and particularly in utero and infancy for
full lung and kidney development.
The full consequences of deficiency in the infant might only be
observed later in adult life
- Pregnancy Safety
CMO (1990) and SACN advise pregnant women to avoid liver and
retinol supplements as an excess (3, 000 ug/day) can cause limb
deformity. Beta-carotene
supplements are considered to be safe.
- However the pattern of vitamin A intake has changed dramatically
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- All Sources = retinol + carotene
from diet + supplements
- The fall in liver and full-fat dairy consumption over the last two
decades has greatly reduced the intake of pre-formed retinol especially
in young women
- The impact of this on pregnancy and infant health is not known
- The rise in obesity and alcohol intake in women might influence vitamin
A metabolism, requirements and the suitability and safety of supplements
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- Stop high intake –supplements, foods (liver & fortified foods)
- Reduce weight if obese or abdominal obesity
- Assess liver and renal function and plasma calcium
- Limit alcohol if excessive or abnormal liver function tests
- Reduce weight if overweight especially if T2D or liver disease
- Assess osteoporosis risk and vitamin D status and treat
- Assess other nutrients excess or deficiency (zinc) and treat
- Review drug treatment (oc pill, tetracycline, sodium valproate)
- Advise against pregnancy
- Reassess after 2-3 months
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- A carotenoid with anti-oxidant activity; 1/6-1/12 converted to retinol
- Cleveage of ingested beta-carotene occurs by action of mono-oxygenase
enzyme in gut wall and liver. Activity of enzyme is genetically
determined and zinc is a co-factor
- >5 portions of fruit and vegetables provides ~ 3.0 mg/day
Average UK intake of 2.7 portions provides 1.8 mg/day providing
approximately 33% of male and 40% of female total vitamin A intake
- Supplements of beta-carotene provide 1-3% of total intake in adults
- Plasma beta-carotene lower in smokers of both sexes and male, not
female, alcohol consumers
- Dietary intake and plasma level correlate negatively with risk of many
cancers and heart disease
- 4 Major trials of beta-carotene (ATBC, CARET, PHS, HPS)
- Beta-Carotene Metabolites enhance DNA damage
Possible difference between synthetic and naturally-occurring
forms
van Helden YG et al. Free Radic Biol Med. 2009;46:299-304
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- Plasma beta-carotene levels are higher in women than men
- Plasma levels are higher in infants and some young adult women
- Plasma beta-carotene levels are lower in male alcohol consumers but
slightly higher in female moderate alcohol consumers
- High intake from diet or supplements can lead to:
- carotenoderma (harmless - may be associated with
amenorrhoea)
- corneal deposition (harmless)
- mild liver damage in alcoholics (supplements)
- increased risks of cancer and possibly vascular disease
(in trials of high-dose
supplements)
- Hypercarotenaemia/ carotenoderma can also be caused by:
- hypothyroidism
- coeliac disease
- protein deficiency/malnutrition
- zinc deficiency
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- 22,071 male physicians
- 50% never smokers, 11% current smokers
- 2x2 factorial design
- Beta-carotene 50 mg on alt. days (BASF, reduced bioavailability)
and Aspirin
- No effect on lung cancer or mortality
- Relatively high baseline beta-carotene levels than in other trials
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- 18,314 men and women
14,254 smoking men and women, 4,060 asbestos-exposed men
- 30 mg beta-carotene and 25,000 IU 7567 ug retinol/day
- Serum beta-carotene rose from 170 ng/ml to 2100 ng/ml
- Supplement group increased rates of death
all causes [1.17]
lung cancer [RR1.46]
cardiovascular disease [RR1.26]
- Beta-carotene may increase the risk of a fatal MI
Rapola et al Lancet 1997;349:1715-20
- It was not possible to differentiate between the effects of retinol and
beta-carotene
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- 29,133 male smokers; average 36 pack-years
- 2x2 factorial design
- 20 mg beta-carotene/50 IU alpha-tocopherol/day for 6.5 years
- Vitamin E: no effect lung cancer [RR 0.98]
- Beta-carotene: no effect lung cancer [RR 1.18; 95% CI 1.03-1.36] and
mortality [RR 1.08; 95% CI 1.01-1.16]
- Risk higher in heavy smokers >20 cigs/day [RR 1.25; CI 1.07-1.46],
light smokers 5-19 cigs/day [RR 0.97; 95% CI 0.76-1.23]
- Alcohol consumers (>11g ethanol/day) increased non-small cell lung
cancer
- Baseline intake and serum beta-carotene were inversely related to lung
cancer risk
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- In UK >200,000 cases of industrial asbestos-related lung disease
- Presentation peaks in 2012 with:
- chronic lung disease
- lung cancer
- mesothelioma.
www.lunguk.org
British Lung Foundation
- Chronic low-level exposure of public sector workers, teachers, nurses
and other hospital staff. BBC
30/10/2008
- Lung cancer and mesothelioma risk in those with industrial or low level
exposure may be increased by supplements of retinol/beta-carotene
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- EVM (2003) set Safe Upper Level set at 7 mg per day
“ ..as a matter of prudence, smokers and those heavily exposed to
asbestos should not take beta-carotene supplements.”
- Beta-Carotene (Healthspan) 15 mg/day
Advice on website
“most nutritionists recommend 15 mg per day for optimal health”.
- “There is no evidence that vitamin and mineral supplements in
reasonable doses are harmful (except when smokers take large doses of
beta-carotene)” no mention of asbestos
Dr TS on Healthspan website, undated, (accessed 11/3/2010)
- NICE (2007) Management for Post Myocardial Infarction
“take no supplements containing beta-carotene”
www.nice.org.uk/nicemedia/pdf/CG48FullGuideline.pdf
- Cardioace (Vitabiotics) 4 mg of beta-carotene/day
No mention of contraindications on product page.
- Beta-Carotene 15 mg/day available from many companies
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- “ .. beta-carotene supplements have not been shown to aid in the
prevention of major chronic disease
“
- “ supplements are not advisable
other than as a provitamin A source for the prevention and control of
vitamin A deficiency in at-risk populations.”
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- Stop supplements especially if smoker or asbestos exposed
- Limit foods – carrots, dark green leafy vegetables, fortified foods
- Assess liver, thyroid function and coeliac disease as appropriate
- Check dietary intake of protein and zinc and advise on diet
- Measure plasma zinc if appropriate and advise on diet/supplements
- Check menstrual status and ? family history of carotenoderma
- Limit alcohol if excessive, overweight or abnormal liver function tests
- Reassure patient about harmless nature especially if a young female
- Review drug treatment (oc pill)
- Reassess after 2-3 months
- Very elevated levels could take >6 months to return to normal
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- Adult intakes average 2.77 – 3.42 [95% CI 1.05-8.11] mg/day
- Food sources: grains (50%), tea, beans, blackberries; supplements 3%
- Deficiency rare but may occur in those fed parenterally
- Glucosamine preparations contain 2 to 8 mg per day [34-45 mg]
- GL 4.0 mg (TSI 12.2 mg) but 0.5 mg (TSI 8.7 mg) if >50 yrs
- 1.03% to 4.86% of dietary manganese is absorbed
- Absorption is approximately doubled in iron deficiency (low serum
ferritin) or by low dietary non-haem iron and little by anaemia
- Absorption requires Divalent Metal Transporter, DMT1, in the gut wall
- Any excess of Mn is excreted via the bile, if liver function is normal
- Up to 1.5 mg of Mn may be retained per day; half-life is 12-36 days
- Manganese excess in the brain can occur as a result of cholestatic liver
disease and is associated with fatigue; it may not be reversible
- High Mn concentration in platelets ? raised in thrombocythaemia
- Iron deficiency and abnormal liver function are common in UK
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- Para 64. “Dietary supplements provide up to 10 mg/day, which if added to
the high level dietary exposure results in a total intake of 290 ug/kg
body weight/day in a 60 kg adult, representing 145% of the EVM guidance
value.”
- Para 65. “The Committee concluded that there was insufficient
information to determine whether there are risks associated with dietary
exposure to manganese”.
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- HSE estimate 60,000 workers have industrial exposure: metal- workers,
welders, those in fertiliser and cosmetics industries
- Manganese salts are used as a flux in welding, Mn fumes can cause lung
inflammation, pneumonia and be absorbed resulting in neurological
effects; assessed by Purdue Pegboard Test
- Replacement for lead anti-knock in petrol is MMT methylcyclopentadienyl
manganese tricarbonyl provides 10 mg Mn/l
- Blackberries contain ~ 15mg/kg but variable range (1-153 mg/kg)
MAFF Multi-element survey of wild edible fungi and blackberries
2000 www.food.gov.uk/multimedia/webpage/maffinfo/2000/maff/2000199
- Mn is occasionally found in well water or water/soil from mining areas
and exposure to these sources can cause health problems
- The Committee on Toxicity (UK) consider that Mn toxicty might be a
problem in children and others, if there is increased bioavailability
from some foods or beverages, or if high doses are taken
www.???
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- Developed at Purdue University
- Standard test of manual dexterity assess both hands
- Used to assess workers suitability for manual tasks e.g in electronics
industry
- Dexterity declines with age
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- Data derived from 323 subjects; controls(106), low-exposure (122) and
high exposure (95) workers in a smelting plant in China
- pMIR expressed as xxx of Mn /yyy of Fe
- Cowan DM et al. Neurotoxicology.
2010;30(6):1214-22
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- Neurology
- Fatigue in patients with liver disease and high blood Mn and MRI changes
Fotron DM et al. Gut 2004;53:587-592
- Neurological problems related to drinking water Mn conc. (1.8-2.3 mg/l)*
Kondakis XG et al Arch Environ Health 1989;44:175-8
- High total intakes of iron and manganese increased risk of PD
Powers KM et al Neurology 2003;60:1761-1766
- Impairment of postural balance and high hair Mn (mean 4.4ug/g)*
Standridge JS et al J Occup Environ Med 2008;50:1421-9
- Reproduction
- Reduced sperm motility and concentration with high blood Mn
Wirth JJ et al Epidemiology 2007;18:270
- Lower Infant Birth Wt assoc. with high (>4.0 ug/dl) or low maternal
blood Mn
Zota AR et al Epidemiology 2009;20:367-73
- Child Development
- Reduced child intelligence and high hair Mn (Mean 471.5 ppb)*
Wright RO et al Neurotoxicity 2006;27:210-6
- Reduced child intelligence and high blood Mn (1.4 ug/l) and high blood
Pb
Kim Y et al Neurotoxicity 2009;30:564-71
- * Increased environmental exposure e.g. proximity to mining/metal works
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- Enzyme cofactor in cartilage
- Two US trials Glucosamine plus
Manganese 34 - 45mg/day
No adverse effect in young subjects over a short period
Leffler CT et al
Mil Med 1999;164(2);85-91
Das A et al Osteoarthrits Cartilage 2000;8(5):343-50
- US Cosamin DS, Mn 9.0 mg/day
- UK Gl’amine /Multis contain 1-5mg
- High Dose Supplements
Nutri many products <60mg/day
Health Plus Zinman 9mg/day
ZMC 15mg/tablet
Lamberts 5 mg x 3/day*
* with warning
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- Identify cause (food, supplements, industrial, well water) and stop
- Limit foods – tea, tinned pineapple, ?blackberries, ?home-grown
- Assess anaemia, platelet count and liver function – alkaline
phosphatase, inflammation and refer to specialist if abnormal
- Assess neurological status – poor co-ordination or gait or reduced
tapping speed; refer to neurologist for MRI scan
- Limit alcohol if excessive, overweight or abnormal liver function tests
- Assess status of other trace elements, zinc, copper and iron and treat
any other deficiencies/excesses
- Consider giving zinc 10mg x 2/day to reduce manganese absorption
- Reassess after 2-3 months, re-measure manganese – whole blood and plasma
zinc and copper
- Elevated levels could take >6 months to return to normal and brain
content is unlikely to fall
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70
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- Adult intakes average 50-100 mg /day + that from supplements
- Food sources: fruit and vegetables, potatoes, food additive
- Increases absorption of non-haem iron
- Mild deficiency common in elderly, smokers or very poor diet
- Many preparations provide 500 -1000 mg
- up to 3 g/day
- GL 1000 mg (haemochromatosis – 500 mg in US)
- At high doses ~20% is absorbed; excess may act as a laxative
- Any excess is excreted in the urine some changed to oxalate
- High doses may increase risk of renal oxalate stones in those who are
predisposed
- I.V. use can precipitate haemolysis in those with deficiency of
Glucose-6 Phosphate Dehydrogenase (Africans/Mediterraneans)
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71
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- EVM set Safe Upper Level set at 1gm per day (2003)
- Increased Plasma Ethinyloestradiol in OC pill users
Effect of 1000 mg per day retarding oestrogen catabolism
Back DJ et al BMJ 1981;282:1516
- Possible increased risk of Breast Cancer in WHI Study
Supplemental, not dietary vitamin C >711 mg/day, RR1.16 [95%
CI: 1.04,1.3]
Cui Y et al AJCN 2008;87:1009-1018
- Multivitamin Use and Breast Cancer in Swedish Women
35,329 mammography negative women followed up for mean 9.5
yr
Multivitamin users RR 1.19 [95% CI: 1.04, 1.37]
Larsson SC et al AJCN 2010;91:1268-72
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72
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- Women’s Health Initiative study in US
Supplement use and cataract formation
Multivitamins RR 1.09 [95% CI: 0.94, 1.25]
Vitamin C alone RR 1.38 [95% CI: 1.12, 1.69]
+ HRT RR 1.56 [95% CI: 1.20,
2.02]
+ Corticosteroids
RR 1.97 [95% CI: 1.35, 2.88]
Rautiainen S et al AJCN 2010; 91:487-493
- Male US Physicians
11,545 >50 yrs:
vitamin C 500 mg/day and or vitamin E 400 IU/alt. days
Vitamin E RR 0.99 [95% CI: 0.88, 1.11]
Vitamin C RR 1.02 [95% CI: 0.91, 1.14]
Christen WG et al Arch Ophthalmol 2010;128:1397-405
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73
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- Adult intakes from food average 50 - 70 ug/day
- Food sources: grains, meat, offal, Brazil and cashew nuts; content of
Brazil nuts can vary widely
French Ref
- Low intake/status associated with increased risk of some cancers and
vascular disease
- Deficiency can occur in animals – miscarriage; sheep are often
supplemented
- Plasma selenium was measured as part of NDNS:
deficiency uncertain but may occur in frail, anaemic elderly and
lower levels in some young people
Bates CJ et al J Trace Elem Med Biol. 2002;16:1-8
- Selenium preparations contain 50 to 200 ug per day
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74
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- Acute toxicity: supplements mg doses:
muscle and joint pains, hair loss, nail changes, sour taste,
garlic breath and neurological problems
- Chronic toxicity: diet or long term supplement use
hair loss dermatitis, bad breath, neurotoxicity
- Excess is excreted via faeces, integument and breath
- Diagnosed by: raised plasma/whole blood or hair Se.
- Possible association between Se. excess and T2D but this may reflect
obesity or altered metabolism
Stranges S et al. 2010
- Safe supplement dose for long term use is probably <100 ug/day
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75
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- Total Body Formula/Total Mega Formula
- Most samples contained 200 times the stated amounts
- Toxic effects were observed after 5 to 10 days of daily ingestion
- Effects included: hair loss, muscle cramps, diarrhoea, joint pains,
deformed finger nails and fatigue
- In total there have been 43 reports from 9 states
- The product has been recalled
- See http://www.thedoctorwillseeyounow.com/content/nutrition/art2036.html
Pictures of selenium excess in humans
|
76
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77
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- Committee on Toxicity 2009.
Measurement of the Concentrations of Metals and other Elements
from the UK Total Diet Study
- www.food.gov.uk/science/surveillance
- EVM (2003) Safe Upper Level 5 ug/kg bw/day
- Acute/chronic toxicity results in nail and hair changes, garlic breath
and neurological problems
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78
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- RDBPC trial of yeast-derived selenium 200ug/day in 1312 participants
- Reduced rates of lung, prostate and colorectal cancers over 7.7 years
- Self-reported T2 diabetes HR 1.55 [95% CI:1.03, 2.23]
- T2D risk greater if baseline Se >121.6ng/ml. HR 2.7 [CI: 1.3, 5.61]
Equivalent to 1.5 umol/l
- Trial results initially lead to large Se/Vit E primary prevention trial
SELECT
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79
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- Supplementation with 200 ug per day results in a substantial rise in
plasma selenium within 3 to 6 months
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80
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- Serum Selenium was measured in 13,887 US adults
- Follow-up mortality data over 12 years
- Serum Selenium levels <130 ng/ml (1.6 umol/l)
Associated with an inverse association between serum selenium and
all-cause and cancer mortalities
- Serum Selenium levels >150 ng/ml (1.9 umol/l)
Associated with a modest increase in all-cause mortality
- No association between serum Se and cardiovascular mortality
- Normal Range:
Serum or Plasma Selenium 80 -150 ng/ml
1.0 -1.9 umol/l
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81
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82
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- Phase III RPCT of:
Se-methionine 200 ug/ and/or
vit E all-rac-alpha-tocopheryl acetate 400 IU daily
4 groups including placebo, intentionally for >7 yrs
- 35,534 men >50/55 yrs (black/white)
- Stopped 2009 after an average of 5.5 yrs
- No reduction in prostate or other cancer risk.
- Se group non-statistically significant increase in T2D
- Statistically significant increases in alopecia and dermatitis.
- Group will continue to be followed for several years
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83
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84
|
- “Evidence suggests that Vitamin E
has blood thinning effects.Vitamin E intakes above 1,000 International
Units, IU, per day may increase
the risk of excess bleeding.
Research suggests that doses up to 800 IU may be safe for
individuals on Coumadin (warfarin), but the evidence is not
conclusive. It is best for those
taking Coumadin to ask their physicians about taking Vitamin E
supplements ”
- NIH Drug-Nutrient Task Force 2003
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85
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- Review and meta-analysis of primary and secondary randomised, controlled
prevention trials
- 47 low-bias risk trials (180,938 participants)
- Effect on all-cause mortality compared with placebo:
All trials - RR 1.07; 95% CI 1.04-1.10
vitamin A - RR 1.16;
95% CI 1.10-1.24
beta-carotene - RR 1.07;
95% CI 1.02-1.11
vitamin C - RR 1.06;
95% CI 0.99-1.14
vitamin E - RR 1.04;
95% CI 1.01-1.07
selenium - RR 0.998;
95% CI 0.997-0.9995
- The adverse effects of beta-carotene, vitamins A and E were dose related
- No apparent benefit for elderly >65 yrs
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86
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- Cause of mortality unknown (mainly vascular disease and cancer)
- Variety of doses and combinations of antioxidants used
- Levels of nutrients were not usually assessed or monitored
- Multivitamin/multimineral preparations were not used
- Trials do no reflect the use of supplements in those with proven
deficiency or in situations of increased need
- But there are very few trials showing any benefit of antioxidants
|
87
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- Adult intakes: mean 233 – 311 [95% CI 96 -562] mg/day
- Food sources: cereals (27%), drinks, meat: supplements 1%
- Deficiency (mild) possible: diarrhoea, diuretics, some women
- Preparations contain 50-300 mg per day
- GL 375 mg
- High intake – reduced absorption and increased urine excretion
- Acute toxicity:
diarrhoea especially if has gastrointestinal hurry
- Chronic toxicity:
if renal impairment – drowsiness, hypotension and death
- 5% to 10% of UK elderly have abnormal renal function
- Excess diagnosed by: raised serum magnesium
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88
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- Acute Toxicity
Minor – gastrointestinal upset – Mg, Fe, Zn,
Severe – large amounts of vitamins A, D, C
- Chronic Toxicity
Osteoporosis – vitamin A
Nervous system – vitamin B6, Mn, Cu
Liver disease – Fe, Cu, vitamin A, beta-carotene
Metabolic Effects – hypercalcaemia, renal stones, induced
deficiency
- Cancer
Induction – antioxidants may act as pro-oxidant
Growth Rate – zinc,
vitamin B
- Adverse Pregnancy Effects
Fetal development/growth – Fe, vitamins A, C and E
- Minor and Idiosyncratic Adverse Effects
Dermatological – beta-carotene, vitamin B12, n-3 EFAs and others
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89
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- Adult intakes average 7.9 – 10.7 [95% CI 3.0 -23.0] mg/day
- Food sources: meat (34%), cereals: supplements 3%
- Deficiency: vegetarians/vegans, alcohol excess, malabsorption
- Preparations contain 5-50 mg per day [150 mg on NHS]
- High intake: reduced absorption and increased urinary excretion
- Acute toxicity:
gastric irritation, nausea, vomiting, metallic taste
GI upset more likely if gastritis, ulcer H.pylori
- Chronic toxicity:
copper deficiency due to trapping of Cu in enterocyte by induced
thionein production (anaemia, neutropenia and neurological problems)
poor immune function
raised cholesterol levels
possibly increased cancer growth- greater risk of more advance
prostate cancer if intake >100 mg/day ref…
- Diagnosis; Pl. zinc, low Pl. copper and neutropaenia/anaemia
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- 53 yr old woman; 4-8 capsules of Zinc gluconate (50mg) >1yr
- Spastic and ataxic gait, tingling and numbness in fingers and feet
- Evidence of a sensory and motor neuropathy in the lower limbs and
decreased vibration and proprioception senses
- Haemoglobin 8.3g/dl (11.7-15.7)
MCV 112.5 uM (80-100)
WBC count 2.6 x103 (3.8 - 10.8)
- Normal vitamin B12, folate, immune function, brain and spine MRI
- Serum copper 7 ug/dl (70-150)
serum zinc 2.28 ug/ml (0.66-1.1)
- Treated with oral copper 2mg per day
Full haematological but only partial neurological recovery
Parenteral copper might be required in severe cases
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91
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- 2004: heavy periods, anxiety, marked premenstrual syndrome [AS]
- Improved with dietary change – low wheat, low sodium, high vegetable,
and supplements of vitamin B and magnesium
- Nov 2006 wholistic doctor, anxiety, period problems & constipation
- Normal TFTs but microsomal antibodies +ve titre 1 in 1600
- Given iron, sulphur, vitamin C iodine ~ 5-10 mg/day
- March 2007 T3 6.9 pmol/l (3-6.5)
and TSH 0.05 mu/L (0.35-5.5)
- May 2007 TSH 27.48 mu/l and fluctuated (1.82 to 9.32 mu/l)
- Late 2007 severe menorrhagia, endometrial ablation unsuccessful,
hysterectomy
- [AS] March 2008 v. anxious, hypertensive, fluid retention on HRT
advised to improve diet, referred back to GP and endocrinologist
- Endocrinologist, commenced on thyroxine – felt much better
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- Adult intakes average 11.6 – 14.0 [95% CI 4.0 – 29.1] mg/day
- Food sources: cereals (44%), meat: supplements F 14%, M 5%
- Deficiency common: vegetarians, menorrhagia and infants
- Multi preparations contain ~15mg /day [OTC 65-100 mg x 3/day]
- GL 14.8 mg
- High intakes result in reduced absorption. No excretion route
- Acute toxicity: abdominal pain, nausea, diarrhoea, constipation
- Chronic toxicity: iron accumulates in the liver, skin, joints, resulting
in fatigue, arthritis, diabetes, gonadal failure
- Haemochromatosis in 0.6% of Europeans - iron accumulation
- Chronic liver disease can also lead to accumulation
- Chronic haematological disorders transfusion haemosiderosis)
- Excess diagnosed by:
raised iron saturation >55% (fasting sample no supplements)
raised serum ferritin (if no inflammation)
not by measurement of Haemoglobin
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93
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|
94
|
- Adult intakes average 1.0 – 1.5 [95% CI 0.31-3.56] mg/day
- Food sources: grains (31%), meat, liver, water: supplements 3%
- Deficiency rare: malnourished, bariatric surgery and zinc excess
- Multivit/mineral preparations contain 1 to 2 mg per day [9 mg]
- GL 1.0 mg (TSI: food + water + supplements = 10.0 mg)
- Any excess is excreted via the bile if liver function is normal
10% to 30% of UK adults/elderly have abnormal liver function
- Acute toxicity: nausea, vomiting
- Chronic toxicity: possible due to
Wilson’s disease 1:20,000 Cu accumulation in the liver, brain due
to transport defect; neuropsychiatric/liver problems <50yrs
Mild cognitive impairment in elderly if diet high in saturated
fat
- Excess diagnosed by:
raised plasma Cu in simple excess if no
inflammation/oestrogen
low plasma, high urine and liver Cu in Wilson’s disease
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95
|
- Adult intakes average 292 – 359 [95% CI 91-754] ug/day
- Food sources: grains (33%), vegets, potatoes: suppls M/F 5/13%
- Deficiency: poor diet, coeliac disease, alcohol excess, elderly
- Multivit/minerals contain 200-400 ug per day [5 mg on script]
routinely given to prevent NTD pregnancy [400-5000 ug/day]
- Added to staple foods in over 52 countries not yet in UK
- Easily absorbed, excess excreted as unmetabolised folic acid UMFA
- Acute toxicity: none
- Chronic toxicity: possible due to
Might mask haematological effects of vitamin B12 deficiency
Un-Metabolised Folic Acid may disrupt normal folate metabolism
Growth promoting effect on some tumors
cf Methotrexate is an anti-folate, anti-cancer drug
- Supplements are given (5 mg x 1 /week) to 600,000 adults in the UK
receiving methotrexate for RA and IBD
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96
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|
97
|
- DBPC Trial 1021 men and women (av. age 57 yrs)
- All had had a colorectal adenoma
- Folic acid, FA, 1000 ug/day or placebo for 5 yrs
- Surveillance colonoscopies at 3ys and 5 yrs
- Adenomas: FA vs Placebo: 44.1% vs 42.4% (3yrs) and 41.9% vs 37.2% (5yrs)
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98
|
- Low intakes of folate increase the risk of alcohol-associated breast
cancer
- Moderate intakes have no effect on risk
- High intakes of folic acid from supplements may increase the growth of
an existing tumor
- The effect of folate/folic acid may be influenced by other nutrients and
genetic factors
|
99
|
- DBPC Trial 238 men and women (av.
age 57 yrs)
- All had had Type 1 or 2 diabetes and mild diabetic nephropathy
- Placebo or daily Folic acid 2.5 mg, vitamin B6 25 mg and vitamin B12 1
mg for a mean of 31.9 months
- Assessment by radionuclide measure of Glomerular Filtration Rate
- Measurement of plasma homocysteine
- Assessment of MI, stroke, need for vascular procedure or all cause death
= composite end point
- Baseline: 89% male, BMI 32.0 kg/m2, very little B12/folate deficiency
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100
|
- Deficiencies of both are common in UK (NDNS 65+)
- Supplement use is associated with better folate status but only slightly
better vit B12 status (Dangour 2008)
- NHANES III in the US: those with a serum B12 <148 pmol/l (~35% of UK
elderly) increasing serum folate was associated with increased HCys and
MMA levels
Selhub J et al Am J Clin Nutr 2009;89(2):702S-706S
- EPIC no overall association of prostate cancer risk and the status of
these nutrients
However in those with a high vitamin B12 level there was an
increased risk of more advanced disease.
Johansson M et al Cancer Epidemiol Biomarkers Prev
2008;17(2):279-85
See also Hultdin J et al Int J Cancer 2004;113:819-24
- Ca Prostate patients are more likely to die from renal failure
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101
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|
102
|
- Thiamin is needed for ribose production, transketolase enzyme, TKTL
- Ribose is a constituent of RNA and DNA and needed for cell growth
- Tumours ferment glucose to produce lactate and ribose in anaerobic
conditions - Warburg effect
- Some cancers upregulate mutated transketolase transcript (TKTL1) and
this may allow enhanced oxygen-independent growth
- Strong expression of TKTL1 in colon and urothelial cancers is associated
with a poorer prognosis
- Anti-thiamin agents are being develop for cancer treatment
- But malnourished cancer patients may develop thiamin deficiency
- Ref Langbein et al British Journal of Cancer (2006)94;578-58
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103
|
- Adult intakes average 809 – 1016 [95% CI 320 - 1783] mg/day
- Food sources: dairy foods (48%), cereals: suppl’nts M1%, F5%
- Deficiency possible: vegans, malabsorption, vit. D deficiency
- Preparations contain 100 - 600 mg per day [600 mg x 2/day]
- GL 1500 mg
- High intakes reduced absorption, increased urinary excretion
- Acute toxicity: diarrhoea from excipients sorbitol or xylitol <5%
- Chronic toxicity:
hypercalcaemia if gross excess and antacids Milk-Alkalai
syndr.
renal stones if predisposed former
cardiovascular disease if no vitamin D supplements
- Excess diagnosed by: raised serum calcium
|
104
|
- Regularly used to treat/prevent osteoporotic fractures
- Used standardly in conjunction with all bisphosphonates
- Large placebo-controlled trial of daily supplements of:
calcium 1000mg
vitamin D3 400 IU (10ug)
36,282 postmenopausal women aged 50-79 years
- Slight improvement in hip bone density
- No reduction in fracture risk
- Increased risk of kidney stone formation - 17%
- NEJM 2006;354:669-682
|
105
|
- Meta-analysis of calcium only trials
- 15 eligible trials only 5 with adequate data
- 8151 participants median follow-up 3.6 years
- Outcomes
Myocardial Infarction HR 1.31 [95% CI 1.02, 1.67]
Stroke HR 1.20 [95% CI
0.96, 1.5]
Composite end point HR 1.18 [95% CI 1.00, 1.39] p = 0.057
- Analysis of other trials 11,921 participants;
Calcium recipients pooled
Myocardial Infarction HR 1.27 [95% CI 1.01, 1.59] p = 0.038
- However, only 3% of NHS prescribed calcium is without vit D!
- Take away message: don’t give calcium by itself
|
106
|
- Adult food intakes average 2.8 - 3.7 [95% CI: 0.2 – 9.7] ug/day
- Food sources: oily fish (24%), meat: suppl’nts M12%, F25%
- Deficiency possible: poor sun exposure, vegans, liver disease
- Preparations contain 2.5 – 25 ug per day [10 ug x 1-2/day]
- Acute toxicity:
Only with massive amounts [MS patients]
- Chronic toxicity:
hypercalcaemia if hyperparathyroidism, sacroidosis, TB,
cancer
present in 1%-0.1% of UK adults mainly aged >60 yrs
- Excess diagnosed by: raised serum calcium
Prudent to check in older patients every 2-5 years
|
107
|
- Vitamin D 1 ng/ml = 2.497 nmol/l
- Institute of Medicine norm = >50 nmol/l
- The reason for slight increase in mortality in high serum vit D is
unexplained
|
108
|
- 18,645 Japanese (69% F) with a total cholesterol >6.5 mmol/l
- Statin (pravastatin 10-20 mg or simvastatin 5 – 10 mg/day) or Statin + 3
x 600 mg EPA ethyl ester /day; mean follow up 4.6 years
- Excluded many with serious diseases or haemorrhage
- EPA reduced major coronary events in those with a history of CAD
|
109
|
- Guidance Levels set by EVM 2003
- Boron 6 mg Uncertain adverse effects
- Nickel 260 ug Could aggravate nickel- sensitive eczema
- Tin 13 mg Uncertain adverse effects
- Cobalt 1400 ug Uncertain adverse effects
- Vanadium 7.5mg Uncertain adverse effects
|
110
|
- Chewable supplements - diarrhoea due to intolerance of
(Calcium and Vit C)
sweetener sorbitol/xylitol
- Multivitamins - skin rashes due to azo dye colouring (Centrum and C50 +)
agent
- Vitamin B3 niacin - flushing due to niacin content
(not nicotinamide)
especially if >50 mg
- Vitamin B2 - yellow discolouration of the urine due
to riboflavin; it is
of no consequence
- Vitamin B Complex - ? Insomnia if taken with 6 hours before bed-time ? Due to high blood
levels
- Malaise ? due to vitamin B intolerance
or variants in metabolism
- Choline - Fishy odour to sweat in those with trimethylaminuria
|
111
|
|
112
|
- Patient - Consumer
Information on pack, point of sale, websites; limited or
misleading
- Professionals
Nutritionists undergraduate training – uncertain
information
Doctors – little training, few NHS supplements, no incentive
Pharmacists/Nutritionists post-grad training – industry sponsored
- Authorities
Food Standards Agency & EFSA reports – no simple
summary
FSA website – only limited information
- Industry
Health Supplement Information Service – errors/omissions on site
HFMA – safety statements but limited and out of date
ERNA – Safety Publication and Fact Sheets – out of
date/inaccurate
- Public – Potential consumers/carers
Advertisements, marketing, books, TV; mixed messages & no
detail
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- Holland and Barrett
- “If you are pregnant, breastfeeding or taking any medication consult a doctor
before use”
- Solgar
“If you are pregnant, nursing, taking any medication or have a
medical condition, please consult your healthcare practitioner before
taking any dietary supplement.”
- Whitehall Laboratories Centrum Silver 50+
- “As with any supplement, if you are pregnant, nursing, or taking
medication, consult your doctor before use.
- Long-term intake of high levels of vitamin A may increase the risk of
osteoporosis in adults”
- Simply Supplements
- “Caution: If under medical supervision please consult a doctor before
use.”
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114
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- Advisory statements written in May 2004 after the EVM Report (May 2003)
- Input from Food Standards Agency and
Health Food Manufacturer’s Association
Council for Responsible Nutrition
Proprietary Association of Great Britain
- Statements apply to some high dose products
- Purpose - protect consumer and allow them to make an informed choice
- Statements will be adopted by HFMA/CRN members
- Statements are based on current evidence and are subject to change in
the light of new evidence.
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115
|
|
116
|
|
117
|
|
118
|
- Health Supplement Information Service
www.hsis.co.uk accessed 19/1/2011
Information for public and media by PR company
- Health Food Manufacturer’s Association
www.hfma.co.uk accessed 19/1/2011
Mission statement 4 “ To
promote high standards of product manufacture and presentation to ensure consumer safety..”
Produced several Safety Advisory Statements
- Council for Responsible Nutrition UK
www.crn.org.uk accessed
19/1/2011
“members all agree to abide by voluntary quality standards to
ensure consumer safety and confidence.”
Expert advisory board. No
reference to Safe Upper Levels but members products are usually low
strength
- European Responsible Nutrition Alliance
www.erna.org
- “ERNA is striving to ensure a future European market with a range of
safe, quality products that reflect the latest in supplementation
research”
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119
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- Retinol
“Safe supplemental daily dose is 1500 ug”
However this is the Total Safe Intake and the figure for
supplements should be 800 ug/day
- Manganese
“Safe supplement daily dose is 4.0 mg”
However no mention that for those aged >50 years the safe dose
is 0.5 mg/day
|
120
|
- Cod Liver Oil and Multivitamins
3 for 2 offers and linked sales can lead to excess retinol intake
- Unnecessary Repeat Sales
vitamin A, selenium and manganese, which can easily accumulate
- Controlling Information
Holland and Barrett no books for sale. Healthnotes on Line US not
UK data
- Marketing via non-Experts (Opticians) of very high dose product
ICAPS Supplement for AMD [Alcon]
Mn10 mg, Zn 60 mg, Cu 4 mg per day
Formula now amended with greatly reduced content (2010?)
- Medical Endorsement
Healthspan - articles by seven doctors with scant mention of
safety
- Nutritional Practitioner Education
Minimal/no safety data provided to practitioner who profits from
sales
Results in “Incentivised Risk” similar to UK banking crisis
- “Good Manufacturing Practice = Safe”
GMP = Quality Manufacture.
It does not mean safe for every consumer
|
121
|
- Trade association for OTC medicine/supplement industry
- Codes for advertising, point-of-sale, website, pack information
- Products have authorised Indications and Warnings
- PAGB Consumer Code:
3.5.1 (16) “Care should be taken not to encourage, either
directly or indirectly, the indiscriminate, unnecessary or excessive use
of any medicine”
- 3.5.3 (30) “ All such advertisements must encourage a cautious approach
to the use of medicines in pregnancy”
- 3.5.4 (33) “Advertising shall not suggest that the safety or efficacy
of a product is due the fact that it is natural”
- 3.5.8 (45) “Advertising shall not state or imply that a product is
recommended or used by a health professional or scientist”
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122
|
- “Marketing is also in the front line of an organisation’s attitude to
social responsibility and corporate citizenship.
Society now expects organisations to ensure that their products
are safe and to communicate any risks or problems clearly to the
consumer”
Preface from Principles of Marketing
2nd Edition Drs. F Brassington & F Pettitt.
Prentice Hall 2000
|
123
|
|
124
|
- Wait for changes to SULs/GLs from EFSA 2011/2?
- HFMA/CRN initiate changes:
Do all members apply label safety statements?
Adverse Reaction reporting “system under development”
Database of major reports on adverse events
- Individual Companies initiate changes – possible
- Do nothing – quite likely for many
- So, how real is industry’s commitment to safety?
|
125
|
- Safety is an unaddressed issue for some current patients
- Insurer Balens (Summer 2010) – will wait for individual cases, no desire
to issue guidance
- Practitioner liability means doing nothing is not an option
- EFSA changes to SULs/GLs will make little difference
- Advice from companies is unlikely to be adequate
- BANT plays a key role in maintaining standards
CPD Criteria - companies should address safety issues: dose
>SUL/GL, duration of use, major contraindications and warnings
Formal Guidance on supplement safety would be helpful
|
126
|
- Cancer Treatment, Herbal and Nutritional Supplements
- Ask patients what they are taking before commencing treatment
- Urge patients to seek professional advice on diet and supplements
- If patients are keen take a good quality one-a-day multivitamin and
mineral; do not exceed the dose
- Antioxidants may reduce the effectiveness of chemotherapy; avoid their
use especially high doses
- Monitor and report any adverse interaction through the Yellow Card
Scheme (www.mhra.gov.uk)
|
127
|
- Alerts, Advisories and Guidelines:
- Coral Calcium – false claims of cure 2004
- Vitamin E and Selenium 2008
no benefit in trials HOPE-TOO, SELECT
13% more heart failure with vit E 400 iu/day
- Anticoagulants and vitamin K interactions 2003
- Infants, possible overdose with vitamin D 2010
- Parkinson’s disease and alternative treatments 2006
- Guidelines on supplements and nutraceuticals 2003
www.aace.com/pub/pdf/guidelines/Nutraceuticals2003.pdf
|
128
|
|
129
|
|
130
|
- Information
Published cases, review articles, adverse events reported to MHRA
- Education
Professionals, Public,
Industry and Media
“ Without a grounding in nutrition it is impossible for anyone to
know whether diets are satisfactory, whether an unfamiliar recipe is
nutritious or not, whether advice in an advertisement or an article in a
newspaper is good advice.”
Magnus Pyke. Preface to Manual of Nutrition 1945
- Regulation
“Regulation is effective, risk-based and proportionate, is clear
about the responsibilities of food business operators, and protects
consumers and their interests from fraud and other risks.“
Food Standards Agency Targets 2010-2015
- Legislation
“Nestle believes that, as a general rule, legislation is the most
effective safeguard of responsible conduct.”
www.nestle.com/AllAbout/All/AboutNestle.htm [26/1/10]
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- Thank you for your participation.
- If you would like a two sides of A4 sheet summarizing the main
contraindications to nutritional supplements please email me dr.stewart@stewartnutrition.co.uk
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