Vitamines et oligo-éléments

ULB – 2011/2012

Certificat de Gastro-entérologie

Vitamins and trace elements

Substances not synthesized by the

organism (or in very small quantities)

but essential for its functioning

Vitamin B1 (thiamine)

• Vitamin B1 (thiamine) is a cofactor for

enzymes involved in AA and CH

metabolism

• Sources: Yeast, pork, rice, legumes

• Absorption in the duodenum

• Deficiency:

– Alcoholics

– Anorexia nervosa

– Bariatric surgery (RYBP)

Clinical spectrum of B1 deficiency

• Beri-beri (malnutrition, bariatric surgery)

• Peripheral neuropathy with sensory and motor

impairments

• Cardiomyopathy, congestive heart failure, tachycardia

• Wernicke-Korsakoff syndrome (alcoholics)

• Wernicke’s encephalopathy: acute form with

nystagmus, opthalmoplegia, ataxia, confusion

• Korsakoff syndrome: chronic condition with short-term

memory loss and confabulation

Galvin et al, Eur J Neurol 2010

Aasheim et al, Ann Surg 2008

Christoforidis et al, AJR 2000

Management of B1 deficiency

• Diagnosis based on clinical presentation

• Lab tests:

• Blood thiamine concentration

• Erythrocyte thiamine transketolase

• Lactate/puryvate ratio (nl <10/1)

• MRI for Wernicke encephalopathy

• IV administration of 100mg thiamine (Vitamine B1

Sterop® 100mg) for 7-14 days followed by per

mouth maintenance therapy (Benerva ® 300mg)

Vitamin B3 (Niacin)

• Pellagra (“raw skin”): photosensitive pigmented

dermatitis, diarrhea and dementia

• Epidemic amongst the corn eating population of SE

USA in the beginning of the 20th century

• Nowadays:

– alcoholics, anorexia nervosa, bariatric surgery, dietary

deficiencies in some regions in China, India, Africa

– Carcinoid syndrome (abnormal metabolism of

tryptophane)

– Prolonged use of isoniazid

• Source: yeast, liver, cereals, seeds

Management of vitamin B3 deficiency

• Ucemine PP ® (Nicotinamide 100mg tablets)

initial dosage: 500-1000mg/day

Vitamin B12 (cobalamin)

• Vitamin B12 (cobalamin) is a cofactor

and coenzyme

– DNA synthesis

– Methionine synthesis from homocysteine

• Animal products (fish, meat, eggs, milk

and milk products, poultry, fortified

breakfast cereals)

• 6-9 µg / day

• According to different diets

Vitamin B12 and food intake

Vegans

0.4 µg

+ milk and

eggs

2.4 µg

+ fish

5 µg

omnivores

7.2 µg

Passive absorption 1-20%

1. Food intake 2. Gastric acid to liberate Cb from binding proteins 3. Pancreatic protease to free Cb from binding to R-factors 4. Secretion of IF from gastric parietal cells 5. Cb-IF receptors in the ileum

Causes of Vitamin B12 deficiency

Dali-Youcef et al, Q J Med 2009

Pernicious anaemia

• B12 malabsorption because of loss of IF secretion

• Prevalence: 2% in the general population • More frequent in the elderly and in

patients with type I diabetes • Characterized by

– Atrophic gastritis – Achlorydria – Hypergastrinemia – IF antibodies – Abnormal schilling test

Food-cobalamin malabsorption

• Decrease in gastric secretion and acidity inability to release cobalamin

from food

• Normal absorption of crystalline free cobalamin

Clinical manifestations

• Large Cb stores compared in relation to daily intake

deficiency takes years to develop

• Neurologic changes – Ataxia (degeneration of the dorsal and lateral spine columns)

– Paresthesis

– Memory loss and personality changes

• Megaloblastic anaemia – Haemolysis

– Low WBC and PLT count

• Glossitis

• Osteoporosis

• Hyperhomocysteinemia – Atherosclerosis

– Venous thromboembolism

Diagnosis

• Lab tests

– Macrocytosis (! Iron deficiency =normal volume)

– IF antibodies (Sn: 50-84%, Sp: 95%)

– High homocysteine levels

• Schilling test

• Upper GI endoscopy

– Atrophic gastritis

B12 supplementation • Parenteral cobalamin (IM)

– Pernicious anemia, malabsorption, ileal resection, gastrectomy

– Dosage: 1mg/day for 7 days, 1mg/week for 4 weeks, 1mg/month

– Vitamine B12 Sterop® (cyanocobalamine, 1 mg/1ml vials)

– Hepavit® (hydroxycyanocobolamine, 5 mg/2ml)

• Oral cobalamin – High dose (1-2 mg/day) in maintenance therapy

• Intranasal (nasal spray) and sublingual forms – Under investigation

Response to B12 supplementation

• After onset of treatment:

– 1-2 days: Hemolysis improves

– 4 days: Hypokaliemia because increase in uptake

– 4 days: Reticulocytosis and decrease in RBC mean

volume

– 10 days: Rise in Hb

– 8 week: Normalisation of Hb

– 3 months: Improvement of neurological symptoms with

maximum at 6-12 months

Folic acid (B9)

• Source: liver, green vegetables, yeast

• Deficiency:

– Alcoholism (inhibition of absorption)

– Poor diet

– Patients with increased requirements

(pregnancy, chronic haemolytic anaemia,

exfoliative skin disease, chemotherapy)

– Patients taking drugs interfering with folate

metabolism (Daraprim, methotrexate)

Acide folique B9

• B9 synthèse méthionine (< homocystéine) et

bases puriques

• Carence en B9 ralentissement des mitoses

– anémie (mégaloblastique)

– troubles immunité

– hyperhomocystéinémie

• risques cardio-vasculaires

• En cas de grossesse :

– défaut de fermeture du tube neural

– retard de croissance intra-utéro

Folic acid deficiency

• Symptoms: – Megaloblastic anemia

– No neurological changes (only in associated B12 deficiency)

• Deficiency can occur within a few months after intake is diminished

• Dosage: – Plasma concentration of folate

• Supplementation: – Oral folic acid (Folavit ® 4mg tablets)

Vitamin C (ascorbic acid)

• Oldest vitamin deficiency described (scurvy)

• Sources: Citrus fruits, tomatoes, strawberries,

spinach

• Strong antioxidant

– Fatty acid transport

– Collagen synthesis

– Neurotrasnmitters

– Prostaglandin metabolism

• Deficiency:

– Severe malnutrition

– Alcohol and drug abusers

Vitamin C deficiency

• Symptoms:

– Ecchymoses

– Bleeding gums

– Impaired wound healing

– Hyperkeratosis

• Supplementation:

– 300-1000 mg daily for 1 month (Redoxon® 500mg)

• Cancer prevention? Not clearly established in RCT

Vitamin D

• Vitamin D is essential in bone

metabolism

• Possible role in decreasing the risk

of other diseases

– Infectious and autoimmune diseases

– Cancers

– Cardio-vascular diseases

Vitamine D

Sources

Alimentation D2 (ergocalciferol) végétaux

D3 (cholecalciferol) produits

d’origine animale

Soleil/peau D3 (< 7-dehydrocholestérol)

Métabolisme

D3 Foie rein (1,25 dihydroxycholecalciferol)

Sources of Vitamin D

• Sunlight

– 5-10 min exposure to sunlight (3000 IU D3)

• Diet

– Salmon (600-1000 IU D3/100 gr)

– Cod liver oil (400-1000 IU D3/tps)

– Egg yolk (20 IU D3)

– Shitake mushrooms (100 IU D3/100 gr)

• Dietary supplements

Holick, NEJM 2007; 357: 266-281

Vitamin D deficiency

• Normal range 20-100 ng/ml • Preferred range 30-60 ng/ml • Groups at risk:

– Elderly – Infants, children and adolescents – Subjects living in higher latitudes – Subjects with dark skin – European countries (no food fortification) – Malabsorption (chronic pancreatitis, IBD, celiac

disease) – Chronic liver disease – Chronic kidney failure – Bariatric surgery

In Belgium

• Recent cross-sectional survey in 401 subjects (40-60 years) living in Belgium for minimum 40 years

• Four different ethnic backgrounds • Autochthonous Belgian

• Moroccan

• Turkish

• Congolese

• 77% (n=306) subjects had vitamin D levels below 20 ng/mL

• Immigrants seemed to be at greater risk

Moreno-Reyes et al, Eur J Nutr 2009; 48: 31-7

Clinical manifestations

• Osteoporosis and bone fractures

• Muscle weakness with increased risk of falls

• Other actions:

• Immunomodulation

• Cell proliferation

• Cardiovascular function

Guidelines to prevent and treat

vitamin D deficiency Prevention Deficiency

Adults

•Inadequate skin

exposure

•Aging (> 50 y)

800-1000 IU Vita D3/day

Or

50,000 IU every 2w or mo

50,000 IU every w

for 8 weeks

Repeat if

necessary

Malabsorption syndroms 50,000 IU every w 50,000 IU every day

or every 2 days

Holick, NEJM 2007; 357: 266-281

One vial of colécalciferol (D3) (D-Cure) 25,000 UI

Drops 10 ml, 2400 IU/ml/30 drops

Is there a need for vitamin D fortification in food?

In case of renal disease 1,25-dihydroxyD3 (1-alpha Leo® 2µgr/day)

Vitamine E

Rôle anti-oxydant

Trace elements

• Minerals that are required in amounts

between 1 to 100 mg/day

• Found in human diet and essential for normal

health and function

• Chromium, copper, fluoride, iodine, iron,

manganese, selenium, zinc

Iron

• Sources:

– Heme iron: meat, poultry, fish

– Non-heme iron: vegetable, fruit,

iron-fortified cereals

• Deficiency

– Microcytic anemia: weakness, headache,

irritability, tachycardia, exercise intolerance

Management

• Oral iron therapy: simple, inexpensive

– First line therapy

• Parenteral iron therapy: complex, expensive, serious adverse effects

– In case of severe intolerance to oral iron therapy or malabsorption

• Blood transfusion

– Active bleeding with hemodynamic instability or end-organ ischemia

Oral iron therapy

• Absorption in the duodenum and proximal jejunum

• In between meals (phosphates, phytates and tannates in food

bind the iron and impair its absorption)

• Avoid concomitant use of anti-acids

• Recommended dose: 150-200mg/day of elemental iron

• Ferrous sulfate (Fe++): better absorption in acidic milieu

– Fero-Grad 500® (105mg Fe++) with ascorbic acid

• Ferric salts (Fe+++):

– Ferricure ®(150 mg Fe+++) tablet or liquid preparation

Response to oral therapy

• Side effects: abdominal discomfort,

nausea/vomiting, diarrhea/constipation (20%)

– Related to the amount ingested

• Within few days of therapy: improved sense of

well-being

• 7-10 days: reticulosis

• 3 weeks: Hb rise of 2 gr/dl

• Normalisation of Hb within 6-8 weeks

Failure to respond to oral therapy

• Coexisting diseases interfering with marrow response – Infection

– Inflammatory disorders

– Malignancy

– Other vitamin deficiency (B12 or folic acid)

• Incorrect diagnosis – Thalassemia

– Lead poisoning

– Copper deficiency

• Lack of compliance

• Lack of absorption – Enteric coated product

– Coeliac disease

– Other medications (anti-acids, tetracycline)

• Continued blood loss

Parenteral iron therapy

• Intravenous administration if major intolerance to

oral forms or malabsorption (IBD, dialysis patients...)

• Fercayl® (Iron dextran) IM (high rate of side effects-

local reaction to anaphylactic shock)

• Venofer® (Iron sucrose) IV

– Vials of 5ml (100mg Fe+++)

– 200 mg = 1 blood unit

– 200 mg 3x/week (maximum dosage)

– Test dose

Zinc

• Usual intake: 4-14 mg/day

• Cofactor in more than 70 enzyme systems

• Important for growth, tissue repair, wound

healing and immune response

• Sources: animal products (meat, seafood, milk)

• Absorbed in the small bowel

Zinc deficiency

• Aetiology

– Dietary zinc depletion (children and adolescents in

developing countries)

– Inherited defect in zinc absorption

– Crohn’s disease

– Cystic fibrosis

– Sickle cell disease

– Liver disease

– Bariatric surgery

Clinical manifestations

• Depressed immunity

• Impaired taste and smell

• Dermatitis (acrodermatitis enteropathica)

• Onset of night blindness

• Alopecia

• Decreased spermatogenesis

Zinc supplementation

• Zinc sulfate tablets 150 mg /day

• Zinc inhibits intestinal absorption of copper! (zinc

toxicity can lead to copper deficiency)

– Preparations containing zinc and copper

Parenteral Nutrition

• Fortification with vitamin complex (Cernevit®) – Thiamine (B1), riboflavine (B2), pyridoxine

(B6), biotin, nicotinamide (B3), panthotenic acid (B5), folic acid, B12,

– A,D, E – No vitamin K (complementary 1 vial/w)

• Trace elements complex (Nonan Novum®) – Iron, zinc, copper, cobalt, manganese, fluoride,

iodine, selenium, molybdene – In case of digestive fluid losses (fistula,

diarrhea, malabsorption) add Zinc and selenium

Gastric restriction and malabsorption

Frequent surgical treatment of obesity

Post-operative

complications

• Malabsorption

• Dumping syndrome

• Vitamin deficiency

Bariatric surgery: RYGB

Mechanisms of nutritional deficiencies

• Insufficient intake

• Decrease in gastric acid secretion (B12 and

iron)

• Duodenal by-pass (main absorption site for

calcium, iron and B1)

• Asynergia between bolus and bilio-

pancreatic secretions (A, D, E, K)

Most frequent deficiencies: iron, B1, folate,

vit D and calcium

Poitou Bernet et al, Diabetes and Metabolism 2007

Before

surgery

3 mo 6 mo 12 mo 18 mo 24 mo Annually

Weight x x x x x x x

Ionogram, calcium x x x x x x x

Blood cell count x x x x x x x

Iron, ferritin x x x x x x

Albumin x x x x x x

B1, folate, B12 x x x x

vitD, PTH x x x x

Osteodensitometry x x x x

Follow-up after RYGB

Poitou Bernet et al, Diabetes and Metabolism 2007

Prevention

• No RCT

• Multivitamin supplements

• Protein intake: 0.8 gr/kg/day

• Supplements of Calcium (1200-1500 mg/day) and

vitamin D (400 UI/day)

• Iron supplements (50-100 mg/day)

• In case of severe or prolonged hair loss: Zinc

• Supplementation on demand according to follow-up

Poitou Bernet et al, Diabetes and Metabolism 2007

Oligo-éléments

• Manganèse :

– carence : rare

– toxicité (en cas de cholestase) : dépôt dans le

cerveau avec pseudo-Parkinson

• Sélénium :

– anti-oxydant

– immunité

• Cuivre : carence : anémie, leucopénie, douleurs

osseuses

• Chrome : carence : résistance à l’insuline

Vitamines Toxicité

Vitamine A hépatopathie

Vitamine D hypercalcémie

B3 (PP) hépatopathie

vasodilatation

B6 (pyridoxine) neuropathie à très forte dose