NUTRACEUTICALS

NUTRACEUTICALS

DR.RACHANA P.R

Outline

Introduction Dietary supplements Probiotics Anti oxidants Nutrients Herbal Medicines Phytochemicals Govt Regulation Limitations

• 75% of people below 40 are

stressed

• 36% are prone to diseases

that affected 50 year-plus

people.

THE TIMES ARE CHANGING

Sleep disorders, lifestyle

diseases such as cancer,

stroke, heart-attack etc are becoming common.

Stress due to competitive

pressures is taking a toll

on children as well.

HABIT IMPACT OUR HEALTH

.

Adverse effects of pharmaceuticals

Increased tendency of patients for self-medication

Aging population

WELCOME THE NUTRACEUTICAL REVOLUTION

The term “Nutraceutical” was coined from “Nutrition” & “Pharmaceutical” in 1989 by

Stephen DeFelice

MD, Founder and Chairman of the

Foundation for Innovation in Medicine (FIM).

“Nutraceutical is any substance that is a food or apart of food and provides medical or health benefits, including the prevention and treatment of disease”.

PREVENTION

DISEASE TREATMENT

HEALTH BENEFIT

PLANT DRUG

FOOD NUTRACEUTICAL

CATEGORIESDIETARY SUPPLEMENTS

Probiotics, Prebiotics, Antioxidants, Enzymes, etc.

HERBAL/ PHYTOCHEMICALS

Herbs or Botanical products.

NUTRIENTS Vitamins, Minerals, Amino Acids, Fatty acids, etc.

DIETARY SUPPLEMENTS

What is a Dietary Supplement?

DSHEA -1994

A product (other than tobacco) intended

to supplement the diet that bears or

contains one or more of the following

dietary ingredients.

Vitamins Minerals Herbs or other botanicals Amino acids Concentrate, metabolite, constituent,

extract or combination of above listed ingredients

Contd…

To supplement the diet by increasing the total daily intake or a concentrate, metabolite, constituent, extract, or combinations of these ingredients.

Intended for ingestion in pill, capsule, tablet or liquid form.

Is not represented for use as a conventional food or as the sole item of a meal or diet.

Is labeled as a "dietary supplement”.

Potentially Useful Supplements

Omega-3 Fatty Acids Phytoestrogens CoEnzyme Q10 Glucosamine/

Chondroitin Sulfate Pre-Probiotics Calcium fortification

Probiotic Products

PROBIOTCS

“ Russian Nobel prize winner and father of modern immunology, Elie Metchnikoff, a scientist at the Pasteur Institute, was the first to conceptualize Probiotics at the start of the 20th century”

Understanding the definitons

Probiotics: A substance that contain micro organisms or bacterias that are beneficial to the host organism.

Prebiotics: (greek -before life) A substance that cannot be digested but does promote the growth of beneficial bacteria.

Symbiotics: ( plus life) a substance containing both prebiotic and probiotics.

History of Probiotics- 1930’s

In early 1930’s, in Japan,

Minoru Shirota developed a fermented milk product called

Yakult

In 1935 he started marketing Yakult as a

probiotic yogurt-like product made by

fermenting a mixture of skimmed milk with

a special strain of Lactobacillus caseishirota

Probiotic microorganisms

Able to survive the passage through the digestive system.

Able to attach to the intestinal epithelia and colonize.

Able to maintain good viability.

Able to utilize the nutrients and substrates in a normal diet.

Non-pathogenic and non-toxic.

Most commonly used Probiotics: Lactobacilli-casei,acidophillus Streptococci -thermophillus Bifidobacteria-bifidum,breve,longum,thermophilum

Possible modes of Action: Competitive exclusion Production of bacteriocins Production of organic acids Altered absorption of the intestinal mucosa

PROBIOTICS

Probiotic Research

Allergies Hypercholestrolemia Colon Cancer-Activate the host’s immune system to

antitumorigenesis. Inhibit bacteria that directly or indirectly convert

procarcinogens to carcinogens. UTI IBD, Antibiotic and Traveller’s diarrhoea Infant formula Acne (maintaining a healthy balance of beneficial intestinal

microflora)

Continued clinical research to study the benefits of probiotics

Obesity and Weight Management (exopolysaccharide producing probiotic strains)

Prevention of osteoporosis (improved bioavailability and absorption of nutrients)

Growth development in children (improved bioavailability and absorption of nutrients)

Treating and preventing respiratory infections, specially in children (boost immune system)

ANTIOXIDANTS

AGING DECREASED IMMUNE

RESPONSE ALZHEIMERS ATHEROSCLEROSIS CANCER

ANTIOXIDANTS

A substance present in low concentration that significantly reduce / inhibit oxidation.

Kinds of Antioxidants

Natural antioxidants: 1.Tocopherols (delta>gamma>beta>alpha)

2.Nordihydroguaretic Acid (NDGA)

3.Ascorbic acid

4.Carotene

Synthetic antioxidants: 1.Butylated Hydroxy Anisole (BHA)

2.Butylated Hydroxy Toluene (BHT)

3.Propyl Gallate (PG)

4.Tertiary Butyl Hydroquinone (TBHQ)

Preventive Antioxidants

Superoxide dismutase Catalase Glutathione peroxidase Singlet oxygen quencher Transition metal chelators (EDTA)

Mechanism of Antioxidants Chain breaking reaction eg. α-tocopherol, which act in

lipid phase to trap free radical. By reducing concentration of reactive oxygen species eg.

Glutathione. By scavenging initiating radicals SOD which act in the

lipid phase to trap superoxide free radicals . By chelating transition metal catalyst: Lactoferrin and

ferritin function to keep iron induced oxidant stress in check

Ceruloplasmin and Albumin as copper sequestrants.

Factors Affecting the Efficiency of Antioxidant

Activation energy of antioxidants to donate

hydrogen should be low.

Oxidation potential should be high .

Reduction potential should be low.

Stability to pH and processing.

Characteristics of Antioxidants

The major antioxidants currently used in foods are monohydroxy or polyhydroxy phenol compounds with various ring substitutions.

These compounds have low activation energy to donate hydrogen.

The resulting antioxidant free radical does not initiate another free radical due to the stabilization of delocalization of radical electron.

Ideal Antioxidants

No harmful physiological effects

Not contribute an objectionable flavor, odor, or

color to the fat

Effective in low concentration

Fat-soluble

Carry-through effect No destruction during

processing

Readily-available

Economical

Antioxidant Research

Oxidative StressSickle CellAtherosclerosis Alzheimer’s Heart failure Macular degeneration Diabetes, Inflammatory diseasesDecreased immune responseAging

NUTRIENTS

Most common Nutrients used/ supplemented as Nutraceutical are:

Vitamins and Minerals. in combination in combination with other antioxidants

Contd…

Contd…

VITAMIN LIKE COMPOUNDS

L- Carnitine: Helps in oxidation of fatty acids, role in oxidative phosphorylation.

Choline: Lipotropic agent, used to treat fatty liver and disturbed fat metabolism.

Inositol: For amino acid transport ,secondary messanger.Bulemia nervosa,OCD,panic disorder/

Taurine: Helps in retinal photoreceptor activity, bile acid conjugation, WBC antioxidant activity, CNS neuromodulation, platelet aggregation, cardiac contractibility, sperm motility, insulin activity.

CHOLINE

Water soluble essential nutrient Grouped with Vit B complex Most available dietary supplement form-LECITHIN Lipotropic agent Smart drug- chemical precursor for acetyl choline

production. Reduce homocystine levels Uses: Alzhiemer’s, Hepatitis, BPD, Alcoholism,

neurodegenerative disorders. Cognitive function?

L-CARNITINE

Latin word “ CARNUS”-flesh ( lysine,methionine) Source- food of animal origin Plays an important role in fatty acid oxidation Energy production. Uses- End stage renal disease Sports medicine- Used /Abused? MI, NASH ,PVD Lipoatrophy in HIV patients treated with anti retroviral

therapy Well tolerated.

MINERALS

Calcium: essential for bone and teeth, maintaining bone strength, nerve, muscle and glandular function, blood clotting

Iron: energy production, Hb, oxygen transport.

Magnesium: for healthy nerve and muscle function, bone formation.

Contd…

Phosphorous: energy production, phosphorylation process, bone and teeth, for genetic material.

Selenium: Antioxidant, functioning of cardiac muscle,RA,Infertility,boost immune system.

Zinc: Essential for cell reproduction, for development in neonates, wound healing, production of sperm and testosterone hormone.

HERBAL MEDICINES

Top Ten Herbal Supplements

St. Johns Wort (Hypericum perforatum) Ginseng (Panax ginseng) Evening prime rose oil Cranberry Green tea Echinacea (Echinacea purpurea) Ginkgo (Ginkgo biloba) Garlic (Allium sativum) Sprulina Aleo vera

GINSENG

Ancient Chinese herb used for over 2000 years and known as the ‘ultimate herb’ among most herbalists.

Uses: Erectile dysfunction, Hepatitis Sedative, sleep aid, depression Enhancer of physical and mental

performance Improves mental concentration

Contd..

Interactions: Anti-

hyperglycemia drugs, MAOIs,

Coffee, Tea.

Common Dosage: • 200-600mg daily , 0.5-2g daily

of dry ginseng root.

Side Effects: Diarrhea,

headache, hypertension,

insomnia, Impotence, nausea,

nervousness , palpitations,

vomiting.

Green Tea

Uses: “ Claims”

1. Prevent oxidative stress-Polyphenols,Catechins,EPGC

2. Cancer prevention

3. Reduce LDL levels

4. Anti aging properties

5. Weight loss

Milk Thistle

Used as a liver tonic for centuries with varying degrees of success

Uses: Antidote for poisonous mushrooms, Hepatitis C, Liver

function aid/ “cleanser”, and Liver repair. Interactions: Nil

Common Dosage: 200-800mg daily

Side Effects: Laxative effects, vaginal bleeding.

Echinacea (Echinacea purpurea)

Uses: Antibacterial, Antiviral, wounds, boost immune system.

Interactions: Not known.

Common Dosage: 85-400mg up to three times daily.

Side Effects: Fairly well-tolerated

GARLIC

Among the most extensively studied herbal supplements to date.

Uses: Anti platelet Athlete’s foot Bacterial infections, constipation Diabetes Fungal infections Heavy-metal poisoning Hypertension Dyslipidemia

Contd…

Interactions: Aspirin

Dipyridamole

Warfarin, Indanavir, Ritinavir

Squanavir.

Common Dosage: 600-900mg daily or up to 4

grams of fresh garlic daily Side Effects:

Dizziness, nausea, skin rash, sweating, vomiting, halitosis.

GINKGO

Uses: Dementia Memory enhancement PVD Premenstrual syndrome Macular degeneration Alzhiemers . Others-Tinnitis,Asthma

Contd…

Interactions: SSRI, Ibuprofen, Anticonvulsants,

Warfarin, Clopidogrel.

Common Dosage:

120-240mg daily

Side Effects: Diarrhoea, headache, seizures,

skin irritation, unusual bleeding or bruising.

St. JOHN WORT

Most scientifically studied herbal supplement on the market over the last 20 years

Uses: Mid to moderate depression Bed-wetting ,Bronchial inflammation Burns Cancer, Hemorrhoids, Insect bites, Insomnia,

Scabies, Digestive issues, Wound healing.

Common Dosage: 100-300mg three times daily

Side Effects: Allergic reactions. Constipation. Dry mouth . Sleep disturbances. Photosensitivity.

CLASS DRUGS

Antiretrovirals NNRTI, PI

Benzodiazepines Alprazolam, midazolam

Hormonal contraception

Combined oral contraceptives

Immunosuppressants

Calcineurin inhibitors, cyclosporine, tacrolimus

Antiarrhythmics Amiodarone, flecainide, mexiletine

Beta-blockers Metoprolol, carvedilol

Calcium channel blockers

Verapamil, diltiazem, amlodipine

TCA,MAO,SSRI Amitryptyline,Phenelzine,Citalopram

Others Digoxin, methadone, omeprazole, phenobarbital, theophylline, warfarin, levodopa, buprenorphine

Phytochemicals

Phytochemicals

Biologically active chemical compounds found in plants.

Not nutrients like vitamins or minerals.

Believed to have health benefits especially related to heart disease and cancer.

Mechanism of action

Phytochemicals could provide health benefits as:

Substrate for biochemical reactions Cofactors of enzymatic reactions Inhibitors of enzymatic reactions Absorbents that bind to & eliminate

undesirable constituent in the intestine Scavengers of reactive or toxic chemicals

Enhance the absorption and / or stability of essential nutrients.

Selective growth factor for beneficial bacteria. Fermentation substrate for beneficial bacteria. Selective inhibitors of deleterious intestinal

bacteria.

Most Commonly Studied Phytochemicals

Food Phytochemical(s)

Allium vegetables(garlic, onions, chives, leeks) Allyl sulfides

Cruciferous vegetables(broccoli, cauliflower,cabbage, Brussels sprouts,kale, turnips, bok choy,kohlrabi)

Indoles/glucosinolatesSulfaforaphaneIsothiocyanates/thiocyanatesThiols

Solanaceous vegetables(tomatoes, peppers) Lycopene

Umbelliferous vegetables(carrots, celery, cilantro,parsley, parsnips)

CarotenoidsPhthalidesPolyacetylenes

Compositae plants (artichoke) Silymarin

Citrus fruits(oranges, lemons, grapefruit)Glucarates

Monoterpenes (limonene)Carotenoids

Other fruits (grapes, berries,cherries, apples, cantaloupe,watermelon, pomegranate)

Ellagic acid Phenols Flavonoids (quercetin)

Beans, grains, seeds(soybeans, oats, barley, brownrice, whole wheat, flax seed)Protease inhibitors

Flavonoids (isoflavones) Phytic acid Saponins

Herbs, spices (ginger, mint,rosemary, thyme, oregano,sage, basil, tumeric, caraway,fennel)

Gingerols FlavonoidsMonoterpenes (limonene)

Licorice rootGreen teaPolyphenols

Glycyrrhizin Catechins

Food Phytochemical(s)

Conclusion

Epidemiological evidence suggest that phytochemicals have some protective effect against GI, lung and prostate cancer.

Further studies with human are required before chemoprevention using phytochemicals can be recommended.

Meanwhile it is prudent to consume relatively large

quantities of fruits and vegetables.

Regulating Agencies

US Food and Drug Administration (FDA)

http://www.fda.gov/Food/DietarySupplements/default.htm

Adverse Events Reporting (AER)

http://www.fda.gov/medwatch

Federal Trade Commission (FTC)http://www.ftc.gov/bcp/index.shtml

Governmental Regulation of Herbal Supplements and Pharmaceuticals

. DSHEA (Dietary Supplement Health and Education Act of 1994): Provides a framework for FDA regulation of dietary supplements• Labeling requirements.• Health claims.• Registration of new ingredients.• Establishment of good manufacturing practices (GMP).

• Regulations for products demonstrating adverse reactions.

Labels Must Include the Following

Statement of identity Net quantity of contents Directions for use Other ingredients in descending order of

predominance Storage conditions, warning label, and expiration

date Name and address of manufacturer or distributor The FDA disclaimer if a structure-function

statement is used

Contd…

Dietary supplements are ONLY allowed to make “structural or function” claims on their labeling.

Only broad statements like ‘glucosamine helps

support healthy joints’ or ‘melatonin helps establish normal sleep patterns’ may be made since the validity of these statements have not been proven in a new drug application/clinical trials for the FDA .

Contd…

Acceptable Claims: Helps maintain function, Promotes healthy cholesterol Supports regularity and immune system Reduces stress

Unacceptable Claims: Protects against heart disease Lowers cholesterol Reduces pain of arthritis Prevents urinary tract infections Helps patients with reduced immune function

TRUTH IN LABELLING

STANDARDIZATION

2007-GOOD MANUFACTURING PRACTICE CGMP Final Rule: The FDA issued the final

rule establishing regulations to require current good manufacturing practices for dietary supplements.

Proper controls to meet quality standards.

Contd…

The requirements include provisions related to the

Design and construction of physical plants that facilitate maintenance

Cleaning Proper manufacturing operations Quality control procedures Testing final product or incoming and inprocess

materials Handling consumer complaints Maintaining records

To limit any disruption for dietary supplements produced by small businesses, the rule has a staggered three-year phase-in for small businesses.

The final CGMPs is effective in June 2008 for large companies. Companies with less than 500 employees have until

June 2009 Companies with fewer than 20 employees have until

June 2010 to comply with the regulation.

Unexpected and undesirable side effects Quality problems, such as unusual odor or colour. Unclear or confusing instructions. Failure to deliver the expected benefit.

Report problems to FDA's MedWatch Adverse Event Reporting Program either online, by regular mail, by fax, or by phone.

In INDIA…

The Indian Health Foods and Dietary Supplements Association ,April 2002.

HADSA-Health Foods & Dietary Supplements Association, 2004.

Consumer benefits, it represents the interests of the manufacturers and suppliers of vitamins, minerals and botanical products including organic and health foods, natural ingredients cosmetics, sports nutrition products

herbs and other dietary supplement.

General Studies’ Limitations for Most Supplements

Number of participants

Different forms of herbal supplements (roots, concentrate, elixir, leafy parts, etc) used sometimes in the same study

No certification that all supplements used meet GMP, or are comparative to begin with

Different species of supplements Short-term studies done (not enough

data) Rarely double-blind, randomized, head-

to-head.

“Let food be thy medicine and medicine be your food“ - Hippocrates ( 460-377BC) THANK YOU