2

Index Introduction……………………………………………………………....3

STEP 1. Establish the Oxidative Stress (OS) Status of the patient……4

STEP 2. A different proposal for each OS status…………………..…..5

STEP 3. General advices…………..……………………………………..9

3

INTRODUCTION

Free radicals induce oxidative stress, which is balanced by the body's endogenous antioxidant

systems with an input from co-factors and by the ingestion of exogenous antioxidants. If the

generation of free radicals exceeds the protective effects of antioxidants, and some co-factors, this

can cause oxidative damage which accumulates during the life cycle, and has been implicated in

aging, and age dependent diseases such as cardiovascular disease, cancer, neurodegenerative

disorders, and other chronic conditions

Concerning antioxidant supplementation and OS the following issues need to be addressed :

1) further assessment of oxidative mechanisms targeted to the aging process physiopathology,

2) easy and precise dedicated instruments of reliable markers of oxidative damage and

antioxidant status,

3)choice of therapeutic schedules of antioxidant supplementation to beneficial,

4) more knowledge of the antioxidant molecules which in several conditions may act as pro-

oxidants.

Accordingly Callegari S.p.A., has invested it’s resources in developing a reliable and easy to

handle Point of Care Instrument for an accurate assessment of both free radicals and the antioxidant

blood pool, related to illnesses, drugs or nutraceutical administration.

In fact, oxidative stress detection allows the development of intervention strategies which can

contribute to delay the progression of a condition/disease as well as to ameliorate the outcome and

then to enhance the quality of life. Therefore, oxidative stress emerges as a novel health risk factor

–particularly if prolonged and associated with other well known risk factors, such as blood

hypertension, high lipid profiles, hyperglycaemia, overweight, and smoking. Measuring the level of

free radicals in your body (testing the FORT assay) and your antioxidant defence (testing the FORD

assay) is a way of preventing the damages associated to oxidative stress and in the case of high

values intervening to reduce damages which may be caused.

But how should you do it1?

1 The information is based on advice from experts in the fields, many years of experience in OS testing and scientific literature. The information is not intended to replace the advise of a licensed health care professional. Callegari does not recommend changing any current medication or starting/adding any new therapies without consulting a fully qualified medical professional.

STEP 1. Establish the Oxidative Stress (OS) Status of the patient

The first and most essential step is to establish the global OS state of the individual. This requires

testing both the free radical action and the antioxidant defences of a patient.

Once the FORT and the FORD have been obtained, the individual OS level is established

allowing assessment of the health of the patient and the most appropriate course of action for that

patient.

The table below is of use to interpret the OS states of individuals based on both the FORT and FORD results. Five major conditions have been depicted.

4

STEP 2. A different proposal for each OS status

Please see notes below.

5

1 WHO guidelines recommend a minimum of 400g daily that is approx 5 servings. Otherwise, it

may be difficult to get all of the vitamins and minerals the body needs. Also, if you eat only one or

two times a day, you may be limiting the number and variety of servings you eat from the various

food groups. In these cases a supplementation should be advised. 1 You could adopt some of the following healthy habits: add some fruit to your breakfast cereals;

grab pieces of fruit or raw vegetables as snacks; eat fruit for dessert; eat a big salad as lunch. 1 It should contain at least vitamin C (approx 500 mg corresponding to 830% of RDA, see also note

11) and E (approx 200 IU corresponding to 660% of RDA) as well as some minerals including

selenium, zinc, copper, manganese.

6

1 Look for products which contain standardized extracts of phytonutrients. Coloured fruits and

vegetables are known to be rich in carotenoids, some of which such as lutein and zeaxanthin tend to

accumulate at the level of the macula. These may include beta- and alpha-carotene, lycopene, citrus

bioflavonoids, quercitin, bilberry (anthocyanins), pine bark (pycnogenol), red cabbage, red wine

concentrate, grape skin, elderberry, green tea, soy isoflavone concentrate, citrus terpene, broccoli,

garlic, rosemary, turmeric, spirulina, aloe vera, ginkgo biloba, papaya, echinacea, as well as bee

products such as pollen, propolis and royal jelly. Dosage is usually suggested by manufacturers

and/or by health care professional. Read product labels carefully and/or ask for details to the

manufacturers. A diet with a strong vegetable component (without having to be a vegetarian)

provides a very broad range of antioxidants and thus appears to be an important defense against

oxidative stress.

Metro & Cow (Clin Terapeutica 2006 157 /6) 597-10) demonstrated the effects of the diet on AC of

individuals: 50 healthy subjects were requested to consume 2-3 fruit portions (especially

pineapple), 3-5 portions of vegetables (especially tomato) and 2-3 glasses of green tea on a daily

basis for approximately 2 months as an addition to a basic diet. Results showed that an antioxidant

rich diet increased both plasmatic total antioxidant capacity and endogenous antioxidant levels

and reduced the lipid peroxidation of membranes, suggesting a reduction of the oxidative stress. 1 Some supplements may interact with prescription and OTC drugs (refer to note 10 too). Some

supplements can have unwanted effects during surgery. For all these reasons, it is important to fully

inform your doctor about the vitamins, minerals, herbals or any other supplements you are taking,

especially before elective surgery. You may be asked to stop taking these products at least 2-3

weeks ahead of the procedure to avoid potentially dangerous supplement/drug interactions - such as

changes in heart rate, blood pressure and increased bleeding - that could adversely affect the

outcome of your surgery.

7

1 Nutrients are not drugs - so do not expect an immediate results. Most people report a positive

improvement in their health within 2-3 months. The most noted effects are increased energy, mental

acuity, emotional stability and better skin that is a general well being. Often the most exceptional

benefits are noted when significant dietary and lifestyle changes are put into action. 1 Strenuous physical exercise especially without appropriate training promotes conditions of OS.

Practice regular but moderate physical activity. It is essential to avoid a sedentary lifestyle, but it is

equally important not to overdo any sport.

1 If not enough sleep is had over a long period of time, it could be useful to take melatonin (2-3 mg

a day). 1 You can take a double dosage of Vitamin C (1 g) and E (400 UI). Antioxidant cocktails may be

also enriched with vitamin B group and A, cofactors such as coenzyme Q10, reduced glutathione,

lipoic acid. 1 Recommended Dietary Allowance (RDA) is the daily dietary intake level of a nutrient considered

sufficient to meet the requirements of nearly all (97–98%) healthy individuals in each life-stage and

gender group. 1 Some supplements may interact with each other as well as with prescription and OTC medicines.

For example: Coumadin (a prescription medicine), ginkgo biloba (an herbal supplement), aspirin

(an OTC drug) and vitamin E (a vitamin supplement) can each thin the blood, and taking any of

these products together can increase the potential for internal bleeding. Combining St. John's Wort

(an herb extract) with certain HIV drugs significantly reduces their effectiveness. St. John's Wort

may also reduce the effectiveness of prescription drugs for heart disease, depression, seizures,

certain cancers or oral contraceptives.

8

9

STEP 3. General advices

1. Supplement programmes should be periodically reassessed: every 2-3 months at the

beginning of treatment and subsequently at least once every 6 months.

Individual requirements should decrease as subjects get healthier but there are conditions

where supplementation may need to be increased:

♦ individuals leading a stressful lifestyle with poor eating habits

♦ women who are pregnant or are planning a pregnancy

♦ women who are breast feeding

♦ children - especially those that are ‘picky’ eaters

♦ individuals on a restricted diet

♦ individuals with a genetic defect and/or malabsorption disorders

♦ individuals recovering from surgery or a serious illness

♦ individuals who rely heavily on stimulants - such as caffeine, alcohol, nicotine and

sugar

♦ the elderly who tend to rely on convenience foods and have poorer appetites.

2. It is essential that supplements are taken under the best conditions, to achieve maximum

absorption, and assimilation by the body. Unless the medical professional has advised

otherwise, it is best to take supplements with one glass of water. See below some

suggestions:

♦ Water Soluble Vitamins: the B vitamins and Vitamin C can be taken on an empty

stomach or with food. Do not take B vitamins in the evening as they may exacerbate

or trigger insomnia.

♦ Fat Soluble Nutrients: vitamins A, D and E, essential fatty acids (omega 3 & 6) and

CoQ10 are best taken with food.

♦ Amino Acids: amino acids are best taken one to three hours away from food.

Minerals♦ : with the exception of zinc, minerals are best taken with food. Calcium and

♦

magnesium are best taken in the evening (and can help you sleep). Special caution

should be taken during iron-based therapies; for example, vitamin C boosts iron

absorption, instead vitamin E improves tolerance of iron supplementation.

Herbs: herbs are best taken with a little food or as a tea. It is best to consult a fully

trained herbalist.

ents are taken, the goal should be3. If supplem stay within the vitamin safety zone, that range

beginning at the RDA11 and ending at a level that is still safe and well below the toxicity

10

4. oxidative stress status, dietary supplements are appropriate in the following

level. It is not easy for a vitamin-consuming public to decide where to draw the line between

safe and excessive micrograms, milligrams or international units, IU. “There are no

officially established limits for maximum doses. There are no reference guides or tables you

can check to see what levels of vitamins trigger harmful effects” says Paul Saltman, Ph.D., a

professor of biology doing research in nutrition at the University of California at San Diego.

"That's because the danger levels vary from person to person and depend on factors such as

weight, health status, metabolism, diet, nutritional status, the form of the nutrient and how

often you take it”. For these reasons, under no circumstances should any supplements be

taken without the expert guidance of a physician. Many supplements contain active

ingredients that have strong biological effects and their safety is not always assured in all

users. Even at lower dosages, always monitor both the FORT and FORD and respect the

feedback your body provides. In addition, if a dietary supplement has been advised in place

of drugs or in combination with any drug, the health care provider should be informed

first6,12.

To avoid

individuals:

♦ vegetarians or vegans. In these cases you may not consume enough calcium, iron,

CLINICAL INVESTIGATION ADVISED:

D FERRITIN HAEMOGLOBIN,

S LEVELS

♦ postmenopausal woman. After menopause, women experience a sudden drop in

foods could benefit from taking a calcium supplement with vitamin D.

zinc and vitamins B12 and D. You can get these nutrients naturally from non-meat

sources, such as fortified soy products, green leafy vegetables, legumes, whole-grain

products and nuts. If you are not able to regularly consume these foods, dietary

supplements may be necessary.

♦ FORT & FORD

♦ BLOOD IRON AN

♦ CALCIUM

♦ PHOSPHORU

estrogen levels, which increases bone loss. To keep bones strong and to decrease

bone loss, you need calcium as well as vitamin D — the vitamin essential for

absorbing calcium. Women who don't obtain enough calcium and vitamin D through

11

♦ BASAL PROLACTIN LEVEL

OXYPROLINURIA

S FROM COLLAGEN DEGRADATION

ES

♦ rals,

including vitamin C, folate, magnesium and calcium. But dietary supplements won't

IGATION ADVISED:

♦ CEA

ANALYSISALPHA-1 ANTITRYPSIN

BLOOD PRESSURE

♦ During pregnancy or trying in in During this

e, rtain nutrients, especially calcium, folate and iron.

ic evidence shows that pregnancy is a condition exhibiting increased

CLINICAL INVESTIGATION ADVISED:

♦ FORD, FORT and URIC ACID

♦ CORTISOL SERUM

♦ URINARY CALCIUM

♦ PHOSPHORUS HYDR

♦ N and C TELOPEPTIDE

♦ ALKALINE PHOSPHATISE

♦ TOTAL CHOLESTEROL, CHOLESTEROL HDL, TRIGLYCERID

smokers. Tobacco decreases the absorption of many vitamins and mine

make up for the major health risks caused by smoking. The safest option is to avoid

all tobacco products.

CLINICAL INVEST

♦ FORT AND FORD

♦ VENOUS HEMOGAS

♦ BREATH FUNCTION TESTS

♦

dividuals attempting to conceive.

tim you need more of ce

Scientif

susceptibility to oxidative stress. In fact doctors usually recommend a dietary

supplement during pregnancy.

12

LINICAL INVESTIGATION ADVISED:

FORT AND FORD

♦ SIDERIMIA

ING

ESSURE GLUCOSE TESTING

♦ g-term excessive alcohol consumption can impair the

inerals, including vitamin B1,

on, zinc, magnesium and folate. Excessive drinking is defined as more than two

♦ FORT AND FORD

♦ WBC

ESTS

CEA,

♦

♦

C

♦

♦ B12 AND FOLIC ACID LEVELS

♦ FERRITIN

♦ HOMOCYSTEINE

♦ URINE TEST

♦ BLOOD PR

Excessive drinkers. Lon

digestion and absorption of several vitamins and m

ir

drinks a day for men under age 65 and more than one drink a day for men over 65

and women. Taking dietary supplements, however, won't make up for the major

health risks caused by excessive alcohol consumption

CLINICAL INVESTIGATION ADVISED:

♦ RBV

♦ HAMEOGLOBIN

♦ IRON FERRITIN

♦ LIVER FUNCTION T

♦

ALPHAFETOPROTEIN GAMMA GT

BLOOD PRESSURE

13

♦ bese people especially with glucose level impairment and high blood pressure.

sychologically, being overweight can affect your body image and damage self-

steem. In some cases this can cause social anxiety and depression.

ommon physical problems include: difficulties breathing, difficulties walking or

besi increases

♦ ORAL GLUCOSE

LOBIN

INARY ELECTROLYTES.

YSIS

• vy prolonged stressful lifestyle and potential

INVESTIGATIO ADVISED:

RRITIN

ECTROPHORESIS

BASAL PROLACTIN

O

P

e

C

running, increased sweating, pain in the knees and back, skin conditions such as acne

These conditions are often known as obesity-related diseases and are some of the

most common causes of death before the age of 75. This is why o ty

your risk of mortality.

CLINICAL INVESTIGATIO ADVISED:

♦ FORT AND FORD

♦ URIC ACID

♦ LOAD GLYCEMIA,

♦ GLYCATE HAMOG

♦ BLOOD & UR

♦ BLOOD PRESSURE

♦ LIPID PROFILE

♦ BODY COMPOSITION ANAL

Hea psychophysical

malnourishment.

CLINICAL

FORT, FORD

URIC ACID

B12 AND FOLIC ACID

BLOOD IRON FE

ALBUMIN

PROTDEMIA AND EL

14

ES

ES

ILE

5. One of an safety of dietary supplements is bioavailability

THYROID FUNCTION T TS

ANTI THYROID ANTIBODI

LIPID PROF

BLOOD PRESSURE

BMI

the issues relating to the efficacy d .

After y ent, it goes through digestive system, where it's

broken down, and eventually enters in bloodstream. Bioavailability is the term used to

describ tively nutrients can be absorbed and used by the body. High

bioavailability means a supplement is easily absorbed. Thereafter, to be truly effective and

ou swallow a vitamin or supplem

e how easily and effec

functional, the bioavailability of a supplement must be higher as much as possible.

Sometimes substances are just naturally well-received by body. Other times the

bioavailability of active ingredients depends on the presence of "enhancers" (e.g., vitamin C

with iron) and "inhibitors" (e.g., iron with zinc and vice versa). Also interactions with drugs

would have an influence. New formulations also have a significant impact on

bioavailability: some manufacturers use special, high-quality ingredients to enhance

bioavailability or new delivery technology such as the system called ‘enteric coating’. This

is a sort of barrier applied to capsule or tablet forming a protective coating that allows it to

reach the intestines without being dissolved in the acidic environment of the stomach. After

passing through the stomach the coating then disintegrates in the small intestine (duodenum)

ensuring high percentage of bioavailability.