Prof. Dr Jean NEVEUniversité Libre de Bruxelles and Superior HealthCouncil

BELGIAN DIETARYREFERENCE VALUES FOR

MICRONUTRIENTS

MINERALS

REVISION OF THE DIETARY

RECOMMENDATIONS FOR BELGIUM AND OF MAXIMAL QUANTITIES

OF SELECTED NUTRIENTS

(VITAMINS AND MINERALS) THAT ARE

ALLOWED IN FOOD SUPPLEMENTS

1997200020032006 2009 2015-16

http://www.css-hgr.be

Health Council of Belgium

Nutrients authorised in food supplements :1. Vitamins : A, B (1 to 6, 12), C, D, E, H, K and M2. Minerals and trace-elements : Ca, Cl, Cr, Cu, Fe, I, Mg, Mn, Mo, P, K, Na, Se, Na, Zn3. Amino acids : ARG, PHE, HIS, ILE, LEU, LYS, MET, THR, TRP, VAL4. Fatty acids : linoleic, linolenic, arachidonic, eicosa-pentaenoic, docosahexanoic

« NOTIFICATION » OF FOOD SUPPLEMENTS

Example : DRV Vit C = 110 mg Food supplements : 16,5 to 330 mg

Nutrients formula are authorized for marketing on theconditions that the supplementary intake due to the dailyrecommended dose is in the range• NOT LESS than 15 % of the Dietary Reference Value

(DRV)• NOT MORE than

• 150 % of the DRV for Vit A and D, Cr, Cu, I, Mg, Mn, K,Se and Zn

• 300 % of the DRV for Vit B, C, E, H and K• 200 % of the DRV for other nutrients

QUALITATIVE AND QUANTITATIVE

« Tolerable Upper Intake Level » Vit C = ~ 2.000 mg 10.000 mg

« EUROPEAN » TOLERABLE UPPER

INTAKE LEVEL

1982

RECOMMENDED DAILY DIETARY INTAKERECOMMENDED

INTAKE

Adequatefor 97,5 %of the population(Population Reference Intake)

AVERAGEREQUIREMENT

Adequatefor 50 %of the population

Lower threshold intake : the level below which almost all individuals will be unable to maintain metabolic integrity, according to the criterion chosen for each nutrient .Average Requirement : the level of nutrient intake that is adequate for half of the people in a population group, given a normal distribution of requirement.Recommended Dietary Intake (Population Reference Intake) : the level that isadequate for virtually all people in the population group.

LOWER THRESHOLD INTAKE

Individual needs

Percentagepopulation

(SUPRA-)NUTRITIONAL INTAKES

Adequate intake : the value estimated when a PRI cannot beestablished because an average requirement cannot bedetermined. The AI is the average observed daily level of intake by a group of apparentely healthy people that isassumed to be adequate

RECOMMENDEDINTAKE

ADEQUATEINTAKE

UPPERLEVEL

AVERAGEREQUIREMENT

Ingested dose

Relative riskfor inadequate

intake

1. Biological functions and impact on health2. Recommended intakes for the different population groups3. Risks involved by an excessive intake with estimation of the maximal tolerable level4. Dietary sources and usual intake by the belgian population ;5. Practical aspects :

• Is there a need (justification) for supplementation?

• Which type of supplementation is applicable : healthy diets, functional foods, foodsupplements, population intervention?

• What is the adequate/optimal dose to use for dietary interventions?

• What is the upper dose not to exceed?

CONTENT OF BELGIAN RECOMMENDATIONS

• Nutrition requires nutritional doses (max. 1-3 times RDI)• Supranutritional doses (also called megadoses) but also infra-

nutritional doses (infinitesimal, catalytic, etc.) are sometimes used in non scientific or poorly validated (therapeutic) approaches

• Excessive doses are potentially dangerous or, at least, not useful:• unexpected undesirable effects

(cancers, cardiovascular diseases)• paradoxical effects

(beneficial -> harmful)• unfavourable interactions with

other nutrients or medications• not absorbed by the GI tract• waste of precious substances

Men taking vit E had a 17 % increased risk of prostate cancer

NB : There are validated« pharmacological » uses for a few micronutrients

NUTRITION IS NOT PHARMACOLOGY

Food supplements are notregistered medicines !

IEDM

NUTRITION AND MISLEADING CONCEPTS• Micronutrition• Nutritherapy• Orthomolecular medicine• Intelligent Nutrition• Neuronutrition…

It’s daylight robbery !

CASE STUDIES I

Ca

NaCr Se

A CLASSICAL PROBLEMNa§ Salt (NaCl) intake : 1 to 26 g/d

§ DRV in adults : max 5 g NaCl (2 g Na)/d, i.e. 2 to 3 timeslower than usual intake (9 - 12 g/d)

§ High Na intake favours HTA (and CVD), particularly inaged, overweighted and salt-sensible subjects

§ Suggested actions :(1) Target the food industry and restauration concerningprocessed and prepared food : bread, cheese,delicatessen (charcuteries), sauces and condiments,ready-made meals and school restaurants(2) Educate the population for better choices, limit salt addition,use of substitutes to salt and eat more fruits and vegetables

Greatly salted food, isn’t it ?

Culturalpatrimonyof UNESCO

FCS 2014/5Mean Na dietary intake of the population (3-64 y) is2,3 g/d (5,8 g NaCl/d), very close to the recommended intake. Such a value probablyreflects an under-estimation of the real situation.

24-h urine collections analysis showed that Na intake is more or less twice as high as the recommended intake. It is substantially higher than that previously calculated on the basis of food consumption data.

Do we eat or not too much Na

CALCIUM Ca§ Important for bone constitution (900 to 1.300 g

Ca) and to several other functions§ Bone solidity is linked to Ca intake but other factors are

involved (physical activity, hormonal status, vitamin Dintake, interactions with other food constituents, etc.)

§ The new dietary recommendations (2016) are differentfrom the previous ones (2009) :

(1) They are more elevated in children and teenagers(2) Recommendations for pregnant and lactating women as wellas elderly are not higher than those for adults

FCS 2014/15Only 22 % of subjects between 3 and 64 years of age have usualCa intakes which satisfy the recommandations (27 % of men and 15 % of women)

Food sources : dairy products, mineral waters, Ca-enriched vegetaldrinks, vegetal sources (green vegetables), sea products, etc.

FCS 2014/15 : Contributions of dairy products and substitutes (49 %); non alcooholic beverages (14 %); Cereals and derivatives(10 %); vegetables (6 %); food supplements (1 %).

Practical recommandations¡ The protective effect against bone fractures is insufficiently

demonstrated in observational and intervention studies;¡ A well-balanced regimen satisfies the Ca needs;¡ Ca and vitamin D are important in the prevention of

osteoporosis (risk of fractures) but the optimal regimensare not fully documented (0,5 to 1,2 g Ca and 800 IU Vit D).The protection is insuffisant in secondary prevention (afterfractures);

¡ When 4 portions or more of dairy products are consumed,dietary complements are not necessary.DG4 = SPF/FOD Belgium, 2017. Proposal for modification of 1992 Royal Decrete :Max 1,6 g in food supplements (AMT EFSA : 2,5 g)

MILD IODINE DEFICIENCY IN BELGIUM

FrançoisDELANGE

1997I

Organised by the Ministery of Health, with the scientificsupport of experts from the Royal Academy of Medicine, the Scientific Institute of Public Health and the Superior Health Council. q Information to health practionners (Medical doctors,

pharmacists, nutritionists, etc.) and of the generalpopulation : starting in 2000 (individual prophylaxis)

q Iodine fortification of bread salt (15 mg iodine/kg salt) : started in 2009 (population level fortification)

q In 2010 : survey of iodine status in school and in pregnant and child-bearing women

PUBLIC HEALTH INTERVENTIONS

Moreno Reyes R, Vanderpas J, Nève J, Vandevijvere S, Van Oyen, H., IDD newsletter, August 2008

Age Gender Iodine, µg/day

7-11 months M/F 701-3 y M/F 904-6 y M/F 90

7-10 y M/F 9011-14 y M/F 12015-17 y M/F 130

Adults (> 18 y) M/F 150Pregnancy F 200Lactation F 200

ADEQUATE INTAKE- Adequate Intake instead of Recommended Intake- Criterion (EFSA, 2014) : goiter prevalence in relation to urinary iodine in

european school-aged children (100 µg/L) extrapolated to dietary intake(150 µg/day)

DIETARY RECOMMANDATIONS

FCS 2014/5Mean I intake of the population is 144 µg/d, very close to the recommended intake. Men ingest more (164 µg) thanwomen (125 µg). Intakeincreased as compared to 2014 (53 µg), but this value wasprobably under-estimated

Dietary recomendations : Insufficient intake is very rare in men (3-64 y) and in girls (3-9 y). No conclusions can be draw for women (10-64 y) Dietary sources :Cereals and derived products49 %; dairy products 16 %; meat 16 %; fish and crustaceans 7 %; foodsupplements 2 %

Pregnant

Not preg.

2014/5

2010

• Belgium is (was ?) a marginally iodine deficient country withpossible consequences in young women and children

• Intervention programs (information to the public and medicalauthorities and iodination of bread salt) led to a significantimprovement of iodine status in children but not in women, including pregnant and lactating women

• Practical recommendations• Dietary choices : marine products, milk, iodised kitchen salt(clear infomation and low price)• Active supplementation of young, pregnant and lactating

women with 50 - 100 µg/d (inform health practitioners) • Continue the large scale intervention program of iodinationof bread salt (motivate bread makers)• Do not make anarchic interventions in the food chain

IODINE : STILL NEEDS ATTENTION

DG4 = SPF/FOD Belgium, 2017. Proposal for modification of 1992 Royal Decrete :Max 225 µg in food supplements (AMT EFSA : 600 µg)

2017

NUMEROUS HEALTH BENEFITS

25 Selenoproteins

Se

Dietary Se intake which satisfies physiological needs (µg/day)

ESSADDI 50 – 200RDA (plasma-GSHPx), 1989 55 – 70Platelet GSH-Px (Nève) 80 – 120WHO/FAO/IAEA:

2/3 expression GSH-Px 21 – 40New Zealand data 90DRI USA (re-interprétation) 55Levelling of plasma Se-protein P 70 – 75Anticancer effets > 200 ?

Selenium as a « nutraceutical »: how to conciliatephysiological and supranutritional effects for anessential trace element ; Nève, J., 5:659-633(2002).

NUTRITIONAL ADEQUACY

NUTRITION REVIEWS; 58(12):363-369 (2000)

SELENIUM AND MORTALITY

USA 3rd National Health and Nutrition Examination Survey (NHNES, 13.887 participants, 6 years) : Se concentrations up to 135 µg/L are associated wih decreased mortality.F Epidemiology and Vascular Ageing study (EVA, 1.389 elderly, 9 years) : low plasma Se at baseline(mean 87 µg/L) is associated with increased overalland cancer mortality.

OPTIMISATION AND SAFETY : CASE STUDYEffects of Selenium Supplementation for Cancer Prevention in

Patients With Carcinoma of the Skin: A Randomized ControlledTrial, Larry C. Clark et al. , JAMA. 1996;276(24):1957-1963

« NUTRITIONAL PREVENTION OF CANCER TRIAL » : 200 µg/day Se or placebo over 4.5 years : 50 % decrease in total cancer incidence; 63 % reduction in prostate cancer; 58 % reduction in colorectal cancer and 48 % reduction in lung cancer.

In 2008, SELECT (started in 2001) showed that Se (200 µg/d as Se-MET) and/or vit E (400 UI/d) did not prevent prostate cancer. The trial was stopped because of lack of benefit.

In 2011, data showed that the men taking vitamin E had a 17 % increased risk of prostate cancer compared to placebo.

In 2014, an analysis showed that men who started the trial with high levels of Se (Se in toenail clippings) doubled their risk of developing a high-grade prostate cancer by taking Se supplements and men who had low levels of Se at the start of the trial doubled their risk of high-grade cancer by taking vitamin E.

Vitamin EPlacebo

• Se is a highly promoted trace element (defense)• Se status is not optimal in about 50 % of Belgians• Beneficial effects are alledged for high Se intakes

but studies demonstrated increased toxicity of Se supplements at moderate doses (200 µg/d)

• The UL of EFSA is potentially harmful (300 µg/d)

• Practical recommendations• Dietary choices (healthy diets) are difficult to

manage for Se• Supplementation of persons with low Se status is

recommended with 50-100 µg Se/d but DO NOT supplement subjects with a rather high Se status

• Supra-nutritional intakes (food + complements) are potentially harmfull (prostate cancer, other cancers)

• Overuse of Se supplements must be avoided

100 µg Se

SELENIUM : THE BIG PROTECTOR ?

STATE OF THE ARTSe recommandations for adults (µg/d)

Health Authority RDI or AI Upper Level Food supplements

< 2000 50-200

France 2001 50-60 150 50-100

USA 2006 55 400 No opinion

Belgium 2009 60-70 300 No opinion

Nordic countries 2012 50-60* 300 No opinion

EFSA 2006 and 2014 70* 300 ( ≥ 100 µg ?)

German countries (D-A-CH) 2015

60-70* No opinion Not recommended

Belgium 2015 70* 200 50-100

* Levelling of plasma Se-protein P is the adopted biomarker for Se adequacy

DG4 = SPF/FOD Belgium, 2017. Proposal for modification of 1992 Royal Decrete :Max 105 µg in food supplements

A CONTROVERSIAL ELEMENT • A lot of methodological difficulties due to

contamination and inaccuracy of determination

• An alledged « key » role in glucose homeostatis and insulin activity but never objectivated (« Glucose Tolerance Factor »)

• No clear deficiency symptoms• No functional or biological

indicators• A lot of not validated alledged

uses (weight loss, physicalactivity)

Jacques VERSIECK and Rita CORNELIS

Cr

REQUIREMENTS / RECOMMENDED INTAKE

The role of Cr an essential nutrient is still unclear. If Cr is an essentialtrace element, it must have a specific role and a deficiency shouldproduce a disease or impairment of function. Methods for evaluatingCr status are lacking, and there is still uncertainty about how Crdeficiency in humans manifests itself. Thus the requirement for Cr isnot currently known.

Attempts to create Cr deficiency have not produced consistentresults, and that there is no evidence of essentiality of Cr(III) innutrition. No Average Requirement and no Population ReferenceIntake for Cr can be defined. Several studies assessed the effect of Crsupplementation on glucose and/or lipid metabolism. After analysis,there is no evidence of beneficial effects associated with Cr intake inhealthy subjects. The Panel concluded that the setting of an AdequateIntake for Cr is also not appropriate.

STATE OF THE ARTCr recommandations for adults (µg/d)

Health Authority RDI or AI Upper Level Food supplements

< 2000 50-200

France 2001 50-70 ND 25-50

USA 2006 25-35 ND -

Belgium 2009 25-35 (250, WHO 1996) 25-50 (No risk)

Nordic countries 2012 Impossible No opinion No opinion

EFSA 2006 and 2014 Impossible Impossible No interest

Belgium 2015 Impossible (MDI: 57-84 *)

(250, WHO 1996) 25-50 (No interestand no risk)

* Median dietary Cr intakes in 17 EU countries (EFSA, 2014)

- Doses to be used in humans could be > 1000 µg/d)

DG4 = SPF/FOD Belgium, 2017. Proposal for modification of 1992 Royal Decret :Max 187,5 µg in food supplements

It seems imperative that (US) Academies find a meansto permanently fund this effort and ensure this work willbe done properly in the future. Because DRIs are thefoundation of essentially every nutritionalrecommendation for the population and of definingnutrient adequacy in all national dietary guidelines,Congress should accept as itsobligation the need to appropriatethe funds necessary for producinghigh-quality, evidence-based DRIs.

November 2016, Vol 105, N°5, 1195-1196