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NUTRACEUTICALS: AN OVERVIEW

Rupesh Borse*1, Neetu Khatri

2, Devendra Gorle

3 and Soniya Mane

4

*1M. Pharm, Dr. D.Y. Patil College of Pharmacy, Akurdi, Pune.

2Assistant Professor, Dr. DY. Patil College of Pharmacy, Akurdi, Pune.

3M. Pharm, Siddhant College of Pharmacy Sudumbare, Pune.

4M. Pharm, JSPM College of Pharmacy Tathawade.

ABSTRACT

Nutraceuticals are the substances which are to be considered as a food

or part of food which possess health benefits including prevention of

diseases and promoting the health. nutraceutical is composed of two

words, one is Nutrition (a nourishing food component) and other one is

Pharmaceuticals (a medical drug). The principal reasons for the growth

of the nutraceutical market worldwide are the current population and

the health trends. Functional food provides the body with the required

amount of vitamins, fats, proteins, carbohydrates, etc. needed for its

healthy survival. When functional food aids in the prevention and/or

treatment of disease and disorders it is called a nutraceutical. The food

products used as nutraceuticals can be categorized as dietary fibers, prebiotics, probiotics,

polyunsaturated fatty acids, antioxidants and other different types of herbal/ natural foods.

The ability of nutraceuticals to influence chronic diseases like diabetes, different types of

cancers, etc. should be recognized as an enormous opportunity in their treatment. They will

play important role in future therapeutic developments. With the advancements in the

qualitative and quantitative determining parameters, the requisition of these products has

been found to be amplified. Due to this, the nutraceutical market has become a million-dollar

industry at a global level.

KEYWORDS: Nutraceuticals, Functional foods, Dietary fibers, Prebiotics, Probiotics.

INTRODUCTION

The term nutraceutical is derived from the word‟s „nutrition‟ and „pharmaceutical‟

Nutraceuticals is a term coined by Dr. Stephen L Defelice in 1989.

World Journal of Pharmaceutical Research SJIF Impact Factor 8.084

Volume 9, Issue 6, 1097-1126. Review Article ISSN 2277– 7105

Article Received on

14 April 2020,

Revised on 04 May 2020,

Accepted on 24 May 2020,

DOI: 10.20959/wjpr20206-17669

*Corresponding Author

Rupesh Borse

M. Pharm, Dr. D.Y. Patil

College of Pharmacy,

Akurdi, Pune.

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Thus, Nutraceuticals are the substances which are to be considered as a food or part of food

which possess health benefits including prevention of diseases and promoting the health.

They consist of nutrients, dietary supplements, specially designed diets or herbal products.

Nutraceuticals are obtained from various sources such as plant and animal and they hold great

opportunities for food industries to bring out novel food catering to future needs. The concept

of nutraceutical was established from the survey in U.K., Germany and France and it stated

that diet is rated more highly by consumer then exercise or hereditary factors to achieving a

good health.

There is a small difference between the functional foods and nutraceuticals. When food is

being prepared using "scientific intelligence" with or without knowledge of how or why it is

being used, the food is called "functional food". Sofunctional food provides the body with the

required amount of vitamins, fats, proteins, carbohydrates, etc. needed for its healthy

survival. When functional food aids in the prevention and/or treatment of disease(s) and/or

disorder(s) other than anemia, it is called a nutraceutical.

Examples of nutraceuticals include fortified dairy products (e.g. milk) and citrus fruits (e.g.

orange juice).[1] [2]

Figure 1: Fortified dairy products.

There are various types of phytochemical constituentspresent in these foods have wide range

of therapeutic effects against a number of diseases like diabetes, heart disease, common cold,

arthritis, cancer, hypertension, dyslipidemia, inflammatory bowel disease, depression etc.

Compounds such as phenylpropanoids, isoprenoids, polyphenols, anthocyanidin‟s,

flavonoids, terpenoids, carotenoids, phytoestrogens and alkaloids etc. possessbeneficial

effects of diet rich in fruits and vegetables.[3]

Nutraceuticals may be classified into natural

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products, functional food and dietary supplements among of these, most rapidly growing

segment is herbal/ natural products followed by dietary supplements.

Generally dietary fibersare obtained from various sources such as fruits, vegetables, whole

grains they are responsible for reducing risk of chronic diseases like cancer and

cardiovascular diseases. A number of phytochemicals as well as other constituents obtained

from plant possess anti-carcinogenic and anti-mutagenic properties. So, these bioactive

compounds are used as chemopreventive substances.[4]

Similarly, soy products and flaxseed have the ability to decrease total and low-density

lipoprotein cholesterol (LDL-C) and increase high density lipoprotein cholesterol (HDL-C)

resulting in reduced risk of cardiovascular diseases (CVDs). CVD risk factors are obesity,

hyperlipidemia, hypertension and diabetes which can be controlled by phytochemicals.[5] [6]

Herbal or plant medicine constitutes an effective source of both traditional as well asmodern

medicines. they are more popular in rural population and around 80% of rural population in

India depends on Herbal or plant medicine for their primary health care.[7]

CLASSIFICATION OF NUTRACEUTICALS

A. BASED ON SOURCE

Table no. 1: Classification based on source.

Source Examples

Plant Tomato, garlic

Animals Shark liver oil, cod liver oil

Minerals Calcium magnesium

Micro- organisms Bifidobacterium, lactobacilli

B. BASED ON CHEMICAL GROUP

Table no. 2: Classification based on chemical group.

Class Examples

Probiotics Helpful bacteria

Prebiotics Digestive enzymes

Dietary fibers Fibers

Antioxidants Natural antioxidants

Fatty acids Polyunsaturated fatty acids

Inorganic mineral supplements Minerals

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C. BASED ON PHARMACOLOGICAL ACTION[8]

Table no. 3: Classification based on pharmacological action.

Action Examples

Anti-oxidant Ascorbic acid

Anti-inflammatory Curcumin

Anti-cancer Genestein

FUNCTIONAL FOOD

According to the International Food Information Council (IFIC), functional foods are “foods

or dietary components that may provide a health benefit beyond basic nutrition.” The

International Life Sciences Institute of North America (ILSI) has defined functional foods as

“foods that by virtue of physiologically active food components provide health benefits

beyond basic nutrition.

As noted by the American Diabetes Association in a position paper dedicated to functional

foods, the term “functional” means food which having some identified value which gives

health beneficial effects, such as reduced risk of disease, to a person consuming it. functional

foods consist of which is obtained from natural sources, such as fruits and vegetables

endowed with antioxidants and fiber, to fortified and enriched foods, such as orange juice

with added calcium or additional carotenoids, to formulated ready-to-drink beverages

containing antioxidants and immune-system supporting factors.

The principle functions of functional food ingredients are related to the maintenance or

improvement of health.[9]

Figure 2: Functional foods.

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All foods consist of adequate number of functional components other than major components

of nutrients which directly or indirectly improve the ones health. Functional food component

are a part of normal diet (proteins, vitamins, carbohydrates), they are not medicine, drugs or

other dietary supplements. fruits, vegetables, cereals, meat, fish, dairy all contains functional

food. Functional food products are not expensive and risky. Many studies regarding to

functional food has confirmed that they great impact for prevention of chronic disease as

most of them are consumed in our daily life. Substance which offer fundamental nutrients

regularly away from quantity obligatory for standard safeguarding, increase, and

improvement of health benefits.[10]

Table no. 4: Functional foods.

Functional foods Functional beverages

Omega fatty acid fortified foods Energy dinks

Probiotic fortified foods Sport drinks

Branded iodinated salts Fortified juices

DIETARY FIBERS

Dietary fiber intake provides many health benefits. However, average fiber intakes for US

children and adults are less than half of the recommended levels. Individuals with high

intakes of dietary fiber appear to be at significantly lower risk for developing coronary heart

disease, stroke, hypertension, diabetes, obesity, and certain gastrointestinal diseases.

Increasing fiber intake lowers blood pressure and serum cholesterol levels.

Increased intake of soluble fiber improves glycemia and insulin sensitivity in non-diabetic

and diabetic individuals. Fiber supplementation in obese individuals significantly enhances

weight loss. Increased fiber intake benefits a number of gastrointestinal disorders including

the following: gastroesophageal reflux disease, duodenal ulcer, diverticulitis, constipation,

and haemorrhoids. Prebiotic fibers appear to enhance immune function. Dietary fiber intake

provides similar benefits for children as for adults. The recommended dietary fiber intakes for

children and adults are 14 g/1000 kcal. More effective communication and consumer

education is required to enhance fiber consumption from foods or supplements.[11]

American Association of Cereal Chemists (AACC) in 2000 defined dietary fibre as the edible

parts of plant or analogous carbohydrates that are resistant to digestion and absorption in the

human small intestine with complete or partial fermentation in the large intestine. Thus, most

appropriately dietary fibre is classified into two categories such as

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water- insoluble/less fermented fibres: cellulose, hemicellulose, lignin

water- soluble/well fermented fibres: pectin, gums and mucilage.

Table no 5: Types of dietary fibers.

Characteristics Fiber content Main food source

Water insoluble

Cellulose Plants(vegetables, sugar beet, various

brans)

Hemicellulose Cereal grains

Lignin Woody plants

Water soluble

Pectins Fruits, vegetables, legumes, sugar

beet, potato

Gums

Leguminous seed plants (gaur locust

bean), seaweed extracts(carrageenan,

alginates), microbial gums(xanthan)

Mucilage Plant extracts(gum acacia, gum

karaya, gum tragacanth)

Application of dietary fibre

i. Addition of soluble and insoluble dietary fibre ingredients influenced the overall quality

(biochemical composition, cooking properties and textural characteristics) of both raw

and cooked pasta. Glucose release is also significantly reduced by the addition of soluble

dietary fibre.[14]

ii. For pastas, the anti-sticking characteristics of certain fibres of oats, barley, soy, rice bran

etc. help to facilitate the extrusion process and may also contribute to dough strength or

improves steam table life of the cooked pasta.

iii. Addition of gums to certain Asian noodle products make the noodles firmer and easier to

rehydrate upon cooking or soaking.

iv. In bread making, the incorporation of fibre ingredients reported to increase the water

hydration values of flour.

v. In case of beverages and drinks, the addition of dietary fibre increases their viscosity and

stability, soluble fibre being the most used because it is more dispersible in water than

insoluble fibre

vi. Oat fibre can be incorporated into milk shakes, instant type-breakfast drinks, fruit and

vegetable juices, ice tea, sports drinks, cappuccino and wine.

vii. Dietary fibres based on pectin, cellulose, soy, wheat, maize or rice isolates and beet fibre

can be used for improving the texture of meat products, such as sausages.

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Table no 6: Functionand benefits of dietary fibre on human health.

Function Benefits

Adds bulk to the diet May reduce appetite

Attracts water in turns into gel during

digestion, trapping carbohydrates and

slowing absorption of glucose

Controls blood sugar levels

Lowers total and LDL cholesterol Reduces chances of heart disease

Regulates blood pressure May reduce onset risk or symptoms of

metabolic syndrome and diabetes

Speeds the passage of food through

digestive system Facilitates regularity

Add bulk to stool Alleviates constipation

Balances intestinal pH and stimulates

intestinal fermentation production of short

chain fatty acids.

Reduces risk of colorectal cancers.

Dietary fibre is naturally present in cereals, vegetables, fruits and nuts. The amount and

composition of fibres differ from food to food. A fibre-rich diet is lower in energy density,

often has a lower fat content, is larger in volume and is richer in micronutrients. This larger

mass of food takes longer to eat and its presence in the stomach may bring a feeling of satiety

sooner, although this feeling of fullness is short term.

It is suggested that healthy adults should eat between 20 and 35 g of dietary fibre each day.

Several non-starch food provide up to 20–35 g of fibre/100 g dry weight and other those

containing starch provide about 10 g/100 g of dry weight and the content of fibre of fruits and

vegetables is 1.5–2.5 g/100 g of dry weight. cereals to be one of the main sources of dietary

fibre, contributing to about 50% of the fibre intake in western countries, 30–40% dietary fibre

may come from vegetables, about 16% from fruits and the remaining 3% from other minor

sources.

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Figure 3: Method of preparation of lemon fiber powder.

The Academy of Nutrition and Dietetics of USA (2015) stated that „the public should

consume adequate amounts of DF from a variety of plant foods‟. Dietary Guidelines

Advisory Committee (2015) recognizes DF as a shortfall nutrient and suggests its under-

consumption in the general public, as in relation to adverse health outcomes, should be

considered as a „public health concern‟. Hence, daily recommended intake levels for DF in

different age groups were proposed in 2010 and 2015 Dietary Guidelines for Americans.[13]

PROBIOTICS

The concept of probiotics probably dates back to 1908, when Noble Prize winner Eli

Metchnikoff suggested that the long life of Bulgarian peasants resulted from their

consumption of fermented milk products.[14]

The term "probiotic" was first used in 1965, by

Lilly and Stillwell for describing substances secreted by one organism which stimulate the

growth of another.[15]

Marteau et al, in 2002 defined them as "microbial preparations or

components of microbial cells that have a beneficial effect on health and well being".[16]

The greatest concentration of commensal organisms is found in the GI tract, which has more

than 400 m 2

of surface area. The GIT harbors a rich flora of more than 500 different bacterial

species, some of which have important health functions, which include stimulating the

immune system, protecting the host from invading bacteria and viruses and aiding

digestion.[17] [18]

The gut flora is acquired rapidly after birth, remains relatively stable

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throughout the life and is essential for human homeostasis. When the intestinal microflora is

developing, the interactions between this microflora with the host results in evolution of a

unique and distinct intestinal immune system.[19]

Definition

The term 'probiotics' was derived from the Greek word, meaning "for life".[20]

An expert

panel commissioned by FAO (Food and Agriculture Organization) and WHO defined

probiotic as "live micro-organisms," which, when administered in adequate amounts confers

a health benefit on the host.[21]

Various bacterial genera most commonly used in probiotic

preparations are Lactobacillus, Bifidobacterium.

Figure 4: Probiotic bacteria.

Lactobacillus rhamnosus GG (LGG) was the first probiotic, which received most clinical

attention to date. Lactobacillusrhamnosus strain GG was discovered in 1985, by developing a

list of ideal qualities for probiotics. Lactobacillus rhamnosus strain GG has proven beneficial

effects on intestinal immunity. It increases the number of IgA and other immunoglobulins

secreting cells in the intestinal mucosa, stimulates local release of interferons.

Table 7: Micro-organisms considered as probiotics.

Lactobacillus

species Bifidobacterium

Other lactic acid

bacteria Non lactic acid bacteria

L. acidophilus B. animalis Enterococcus faecalis Saccharomyces cerevisiae

L. casei B. adolescentis Enterococcus faecium Saccharomyces boulardii

L. crispatus B. bifidum Lactococcus lactis E. Coli strain nissle

L. rhamnosus B. breve Leuconostocmesenteroides Propionibacteriumfreudenreichii

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Properties

For adequate amount of health benefits, a dose of five billion colony forming units a day

(5x10 9 CFU/day has been recommended, for at least five days. The microorganisms used in

probiotic preparations should be generally recognized as safe (GRAS), they should be

resistant to bile, hydrochloric acid and pancreatic juice, have anti-carcinogenic activity and

stimulate immune-system, have reduced intestinal permeability, produce lactic acid, able to

survive both acidic conditions of the stomach and alkaline conditions of the duodenum.

Foods for human consumption that contain mainly lactic acid bacteria include fermented

milks, cheeses, fruit juices, wine, and sausages. Single and mixed cultures of live

microorganisms are used in probiotics preparations.

Mechanism

Gastrointestinal mucosa is the primary interface between the external environment and the

immune system. Whenever intestinal microflora reduces, antigen transport is increased

indicating that the normal gut microflora maintains gut defences. The non-pathogenic

probiotic bacteria interact with the gut epithelial cells and the immune cells to start the

immune signals. These bacteria must interact with M cells in the Peyers patches, with gut

epithelial cells, and with associated immune cells.

Figure 5: Mechanism of action of probiotics.

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Probiotic bacteria have been shown to modulate immunoglobulin production. Secretory IgA

plays an important role in mucosal immunity, contributing to the barrier against pathogenic

bacteria and viruses. The increase in the number of IgA producing cells was the most

remarkable property induced by probiotic organisms and also by fermented milk yogurt.

Probiotics have been shown to be effective in varied clinical conditions- ranging from

infantile diarrhoea, necrotizing enterocolitis, antibiotic associated diarrhoea, relapsing

Clostridium colitis, Helicobacter pylori infections, inflammatory bowel disease to cancer,

female urogenital infection and surgical infections.[7]

Probiotics have preventive as well as curative effects on several types of diarrhoea of

different etiologies. Prevention and therapy of diarrhoea have been successfully investigated

for numerous dietary probiotics micro-organisms.

Rota virus diarrhoea - Lactobacillus rhamnosus strain GG and Bifidobacterium lactis BB-

12 for prevention and Lactobacillus reuteri SD 2222 for treatment of acute diarrhoea caused

by rota virus in children.

Radiation induced diarrhoea - probiotic lactic acid producing bacteria are an easy, safe and

feasible approach to protect cancer patients against the risk of radiation.

Traveller's diarrhoea- Traveller's diarrhoea is a common health complaint among travellers.

Saccharomyces boulardii and a mixture of Lactobacillus acidophilus and

Bifidobacteriumbifidum had significant efficacy.

H.pylori. is a major cause of chronic gastritis and peptic ulcer and a risk factor for gastric

malignancies. Probiotics had an in vitro inhibitory effect, reduced H. pylori associated gastric

inflammation in animals, improved H. pylori associated gastritis and also probiotic treatment

reduced H. pylori therapy associated side effects.

Inflammatory bowel disease

Inflammatory bowel disease classically includes ulcerative colitis and Crohn's disease

representing different patterns of chronic inflammation of GIT. Thus, probiotics have a

potential for inducing or maintaining remissions in IBD.

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Cancers

in intestinal tumour‟s, prevention or delay of tumor development by lactobacilli is that they

bind to mutagenic compounds in the intestine and also suppress the growth of bacteria which

convert procarcinogens into carcinogens.

Other benefit

Role in uro-genital infections-

Two strains, Lactobacillus GG (ATCC 53103) and Lactobacillus rhamnosus GR-1 appear to

be effective at colonizing and protecting urogenital tract.

In this direction, the administration of Lactobacillusrhamnosus and L. fermentum RC-

14 for prevention and treatment of uro-genital infections. By reducing the risk of bacterial

vaginosis, probiotics may also help to reduce infant mortality and pre-term labour in

pregnant women.

Role in prevention of transmission of AIDS and STDs

Lactobacilli play a critical role in the regulation of the vaginal microflora. It has been

suggested that the production of H2O2 rather than a particular species of Lactobacillus, is

essential in the regulation of the vaginal flora.

Antibacterial effects

Different Probiotic agents against several pathogens, including Listeria monocytogenes,

Salmonella, typhimurium, E. coli and H.pyloriamong others. Therefore, probiotic agents may

provide prototypic antimicrobial substances that will be useful for pharmaceutical companies

in the development of new antibiotics.

Role In oral candidiasis- B. animalis was found to reduce the incidence and severity of

mucosal candidiasis.

probiotics have an important emerging role in managing critical illnesses originating in

gastrointestinal tract like acute pancreatitis. Probiotic Lactobacillus reuteri reduces

gingivitis and decreases gum bleeding.

Probiotics in allergic diseases -Most studies on the use of probiotics have assessed

patients with atopic eczema. Also, work has been carried out on the role of probiotics in

respiratory allergies like asthma.

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Lactic acid produced by Lactobacillus can be used as food preservative, flavouring agent

andemulsifier.

FAO/WHO developed Operating Standards in 2002, which gave guidelines for

allcompaniesproducing probiotic products.

These guidelines include

1. Implementation of guidelines for use of probiotics.

2. Phase I, II and III clinical trials to prove health benefits that are as good as or better than

standard prevention or treatments for a particular condition or disease.

3. Good manufacturing practice and production of high-quality products.

4. Studies to identify mechanism of action in-vivo.

5. Informative/precise labelling.

6. Development of probiotic organism that can carry vaccines to hosts and /or antiviral

probiotics.

7. Expansion of proven strains to benefit the oral cavity, nasopharynx, respiratory tract,

stomach, vagina, bladder and skin as well as for cancer, allergies and recovery from

surgery/injury.[24]

ANTIOXIDANTS

Oxygen is absolutely essential for the life of aerobic organism but it may become toxic if

supplied at higher concentrations. Dioxygen in its ground state is relatively unreactive; its

partial reduction gives rise to active oxygen species (AOS) such as singlet oxygen, super

oxide radical anion, hydrogen peroxide etc. This is partly due to the oxidative stress that is

basically the adverse effect of oxidant on physiological function. Free radicals are an atom or

molecule that bears an unpaired electron and is extremely reactive, capable of engaging in

rapid change reaction that destabilize other molecules and generate many more free radicals.

These radicals are highly toxic and thus generate oxidative stress in plants. Plants and other

organism have in built wide range of mechanism to combat with these Free Radical

problems. In plants and animals these free radicals are deactivated by antioxidants. These

antioxidants act as an inhibitor of the process of oxidation, even at relatively small

concentration and thus have diverse physiological role in the body.

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Antioxidant constituents of the plant material act as radical scavengers, and helps in

converting the radicals to less reactive species. A variety of free radical scavenging

antioxidants is found in dietary sources like fruits, vegetables and tea, etc.

Antioxidants are believed to play a very important role in the body defense system against

ROS In another term antioxidant is “any substance that, when present at low concentrations

compared with that of an oxidizable substrate, significantly delays or inhibitsoxidation of that

substrate.

Natural antioxidants occur in all parts of plants. These antioxidants include carotenoids,

vitamins, phenols, flavonoids, dietary glutathione, and endogenous metabolites. Plant-derived

antioxidants have been shown to function as singlet and triplet oxygen quenchers, free radical

scavengers, peroxide decomposers, enzyme inhibitors, and synergists. The most current

research on antioxidant action focuses on phenolic compounds such as flavonoids. Fruits and

vegetables contain different antioxidant compounds, such as vitamin C, vitamin E and

carotenoids, whose activities have been established in recent years. Flavonoids, tannins and

other phenolic constituents Present in food of plant origin are also potential antioxidants.

These components include:

Nutrient-derived antioxidants like ascorbic acid (vitamin C),

tocopherol and tocotrienols (vitamin E), carotenoids,

Low molecular weight compounds such as glutathione and lipoic acid.

Antioxidant enzymes, e.g., super oxide dismutase, glutathione peroxidase, and glutathione

reductase, which catalyse free radical quenching reactions. Metal binding proteins, such as

ferritin, lactoferrin, albumin, and ceruloplasmin that sequester free iron and copper ions that

are capable of catalysing oxidative reactions. Numerous other antioxidant phytonutrients

present in a wide variety of plant foods.[25]

Sources of antioxidants

Vitamin A: Dairy produce, eggs.

Vitamin C: berries, oranges, and bell peppers.

Vitamin E: Nuts and seeds, sunflower, vegetable oils, and green, leafy vegetables

Beta-carotene: Brightly coloured fruits and vegetables, such as carrots, peas, spinach,

and mangoes.

Lycopene: Pink and red fruits and vegetables, including tomatoes and watermelon.

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Figure 6: Classification of antioxidants.

Carotenoids

Carotenoids are a family of over 600 fat-soluble plant pigments, approximately 20 of which

are present in human tissues and blood. They are potent reactive oxygen species (ROS)

scavengers, protecting the skin from oxidative stress. Humans and animals cannot synthesize

carotenoids, so they must obtain them via ingestion of foods or supplements. Skin

concentrations of carotenoids increase with ingestion of the components, but decrease with

oxidative stress and UV exposure.[3]

Here, we focus on four of the major dietary carotenoids:

β-carotene, lycopene, lutein, and zeaxanthin.

1. β-Carotene

β-Carotene is a precursor to vitamin A. It protects cells from damage by inhibiting free

radical and singlet oxygen-induced lipid peroxidation. It also has photoprotective properties,

which increase the minimal erythema dose (MED), and protects against sunburn development

and photosuppression of the immune system. Foods rich in β-carotene are green leafy

vegetables, orange root vegetables, and yellow or orange fruit. Long-term β-carotene

supplementation has been associated with an increased risk of lung cancer, so further studies

are needed to determine the optimal daily allowance while accessing for supplementation

health risks.

2. Lycopene

Lycopene has no vitamin A activity, but is considered the best singlet oxygen quencher in the

carotenoid family. Studies have shown that consumption of tomato paste, which is high in

lycopene, significantly lowers UV-induced erythema and it inhibits proliferation of several

types of cancer cells via cell-cycle arrest and induction of apoptosis. Foods rich in lycopene

are tomatoes, pink grapefruit, and watermelon.

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3. Polyphenols

Polyphenols are secondary metabolites of plants and are found predominately in fruits,

vegetables, cereals, and beverages. For years, polyphenols have been of interest for their

antimutagenic, anticarcinogenic, anti-inflammatory, and antioxidant properties.

4. Curcumin

Curcumin is a polyphenol derived from the turmeric spice. Curcumin serves many

biologically active roles, as anticarcinogenic, anti-inflammatory, and antioxidant roles.

Curcumin has been suggested as a potential treatment for cancer because of its ability to

hinder the production of cancer cells and encourage apoptosis. It has been shown to promote

cell death by influencing the expression of p53 and decreasing the production of nuclear

factor kappa B.

5. Vitamins

a) Vitamin C

Vitamin C is a water-soluble compound. Vitamin C is a powerful antioxidant and free radical

scavenger that protects our tissues, cell membranes, and DNA from oxidative damage.

Vitamin C also decreases the malondialdehyde content in the skin, which is a marker of

oxidative stress. Food sources containing the highest concentrations of vitamin C are raw red

and green peppers, oranges, grapefruits, kiwifruit, broccoli, strawberries, and Brussels

sprouts.

b) Vitamin E

Vitamin E is a group of fat-soluble compounds. The most abundant and biologically active

form of vitamin E, alpha-tocopherol (αT), is the leading form used in human metabolism .αT

protects the skin from UVB damage by halting the formation of ROS, scavenging free

radicals, stabilizing the surface and membranes of cells, reducing the number of apoptotic

cells, and minimizing the activation of nuclear factor kappa B.

6. Astaxanthin

Compared to vitamin C and β-carotene, astaxanthin is a more powerful antioxidant capable of

neutralizing cellular reactive oxygen species. astaxanthin has been shown to be 6,000 times

more powerful than vitamin C, and 5 times more powerful than β-carotene Astaxanthin is

lipid-soluble, and due to its molecular structure, it‟s able to more efficiently sequester free

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radicals. Synthetic forms of astaxanthin are available, however natural sources have been

shown to be most effective.[26]

Prebiotics

Prebiotic act as a nutrient source for the good probioticbacteria. This encourages the probiotic

bacteria to grow in a favourable environment. Inulin is a prebiotic that has been widely used

in processed foods.[27]

The prebiotics concept was introduced for the first time in 1995 by Glenn Gibson and Marcel

Roberfroid. International Scientific Association of Probiotics and Prebiotics (ISAPP) defined

“dietary prebiotics” as “a selectively fermented ingredient that results in specific changes in

the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s)

upon host health”

Types of prebiotics

1. Fructans

This category consists of inulin and fructo-oligosaccharide or oligofructose.

Previously, some studies implicated that fructans can stimulate lactic acid bacteria

selectively. However, over recent years, there are some investigations showing that the chain

length of fructans is an important criterion to determine which bacteria can ferment them

Therefore, other bacterial species can also be promoted directly or indirectly by fructans.

2. Galacto-Oligosaccharides

Galacto-oligosaccharides (GOS), the product of lactose extension, are classified into two

subgroups: (i) the GOS with excess galactose at C3, C4 or C6 and (ii) the GOS manufactured

from lactose through enzymatic trans-glycosylation.

GOSs can greatly stimulate Bifidobacteria and Lactobacilli. Bifidobacteria in infants have

shown high incorporation with GOS. Enterobacteria, Bacteroidetes, and Firmicutes are also

stimulated by GOS, but to a lesser extent than Bifidobacteria.

3. Starch and Glucose-Derived Oligosaccharides

There is a kind of starch that is resistant to the upper gut digestion known as resistant starch

(RS). RS can promote health by producing a high level of butyrate.so it has been suggested to

be classified as a prebiotic. An in vitro study demonstrated that RS could also be degraded

by Ruminococcusbromii and Bifidobacteriumadolescentis.

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4. Other Oligosaccharides

Some oligosaccharides are originated from a polysaccharide known as pectin. This type of

oligosaccharide is called pectic oligosaccharide (POS). They are based on the extension of

galacturonic acid (homogalacturonan) or rhamnose (rhamnogalacturonan I).

5. Non-Carbohydrate Oligosaccharides

Although carbohydrates are more likely to meet the criteria of prebiotics definition, there are

some compounds that are not classified as carbohydrates but are recommended to be

classified as prebiotics, such as cocoa-derived flavanols. In vivo and in vitro experiments

demonstrate that flavanols can stimulate lactic acid bacteria.

Production of prebiotics

Because of their low concentration in foods, they are manufactured on industrial large scales.

Some of the prebiotics are produced by using lactose, sucrose, and starch as raw material.

Since most prebiotics are classified as GOS and FOS regarding industrial scale.

For FOS production, the whole cell of a microorganism or free enzyme can be used. Thereare

different factors that can affect the concentration of produced FOS. β-fructofuranosidase is

capable of converting sucrose to FOS. The glucose produced during FOS fermentation is

converted to gluconic acid by glucose oxidase. GOS were first chemically synthesized by

nucleophilic and electrophilic displacement, but this method is currently deemed to be

uneconomical at the industrial scale. The key enzymes for GOS formation are galactosyl-

transferase and galactosidase.

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Figure 7: Production of prebiotics.

Formation of GOS by means of galactosidase is much cheaper than galactosyl-transferases.

However, galactosidase produces GOS in lower quantities, the amount of GOS produced by

galactosidase can be improved in different ways:

(i) increasing the concentration of donors and acceptors in the reaction,

(ii) lowering water activity of the reaction,

(iii)shifting the reaction equilibrium to the end product direction by the product elimination in

the medium

(iv) altering the synthesis conditions

Prebiotics Mechanisms for Alteration of Gut Microbiota

By the provision of energy sources for gut microbiota, prebiotics are able to modulate the

composition and the function of these microorganisms. Distant bacterial species in phylogeny

share their skills to consume a specific prebiotic regularly.

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Figure 8: Mechanism of action of prebiotics.

A. Prebiotics and Gastrointestinal Disorders

1. Irritable Bowel Syndrome and Crohn’s Disease

There are a few studies about the effects of prebiotics on irritable bowel syndrome (IBS) and

Crohn‟s disease. IBS is a gastrointestinal syndrome characterized by chronic abdominal pain

and altered bowel habits in the absence of any organic cause. Crohn‟s disease is a type of

chronic, relapsing inflammatory bowel disease (IBD), which can involve any part of the

gastrointestinal tract from the mouth to the anus. It has been reported that in both IBS and

Crohn‟s disease, the Bifidobacteria and Faecalibacteriumprausnitzii population along

with Bacteroides to Firmicutes ratio were decreased.

2. Colorectal Cancer

Colorectal cancer, is a multi-step disease from genetic mutation to adenomatous polyps,

which then leads to invasive and metastatic cancer. In addition, a clinical trial demonstrated

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that symbiotic therapy (Lactobacillus rhamnosus and Bifidobacterium Lactis plus inulin)

could reduce the risk of colorectal cancer by reducing the proliferation rate in colorectal,

inducing colonic cells necrosis, which leads to improving the integrity and function of

epithelial barrier.

3. Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) is a gastrointestinal emergency condition primarily in

premature neonates, in which portions of the bowel undergo necrosis. Since prebiotics, such

as FOS and GOS, can stimulate the growth of gut microbiota (e.g., Bifidobacteria) and reduce

the pathogenic bacteria in preterm infants, it is claimed that they can prevent NEC.

B. Prebiotics and the Immune System

Consuming prebiotics can improve immunity functions by increasing the population of

protective microorganisms. Animal and human studies have shown that prebiotics can

decrease the population of harmful bacteria by Lactobacilli and Bifidobacteria. For example,

mannose can reduce colonization of pathogens by promoting mannose adhesion

to Salmonella.

The details of well-known prebiotic effects on the immune systems are discussed below:

I-Oligofructose and inulin mixture: The mixture of oligofructans and inulin can improve

antibody responses toward viral vaccines, such as influenza and measles.

II-FOS: improvement of antibody response to influenza vaccine following FOS

consumption. Moreover, the side effects of the influenza vaccine are reduced.

III-GOS: GOS increased the blood level of interleukin 8 (IL-8), interleukin 10 (IL-10),

and C-reactive protein in adults, but decreased IL-1β. It has been found that the function

of NK cells improves by consuming GOS. In infants, GOS reduces the risk of atopic

dermatitis and eczema.

IV-AOS (acidic oligosaccharides): The possibility of atopic dermatitis is reduced by AOS

in low-risk infants.

C. Prebiotics and the Nervous System

I-Neural Pathway: Some prebiotics, such as FOS and GOS, have regulatory effects on

brain-derived neurotrophic factors, neurotransmitters (e.g., d-serine), and synaptic

proteins (e.g., synaptophysin and N-methyl-D-aspartate or NMDA receptor subunits).

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II-Endocrine Pathway: prebiotics act as a regulator of other hormones, such as plasma

peptide YY

Figure 9: Prebiotics effect for health maintenance and protection against disorders.

III-Immune Pathway: prebiotics are also capable of influencing mood, memory, learning,

and some psychiatry disorders by changing the activity and/or composition of gut

microbiota.

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D. Prebiotics and Cardiovascular System

Prebiotics are able to lower the risk of CVD by reducing the inflammatory elements. an

improvement in the lipid profile by consuming prebiotics. They decreases blood

triacylglycerol (TAG) and liver lipogenesis.

Bimuno® Galacto-oligosaccharides (B-GOS) administration for 12 weeks decreased

circulating cholesterol, TAG, and total: HDL (high-density lipoprotein) cholesterol ratio.

Paradoxically, prebiotics may have a detrimental effect on lipid profile through producing

some SCFAs, such as acetate. Acetate can be converted to acetyl-CoA, which is a substrate to

synthesize fatty acids in hepatocytes.

E. Prebiotics and Calcium Absorption

Prebiotics dietary fibers on the absorption of minerals, such as calcium, but the results are

conflicting consumption of lactulose, TOS or inulin + oligofructose in doses ranged between

5 to 20 g/day significantly absorb calcium absorption.

Digestive enzymes

Figure no 10: Mechanism of action of digestive enzymes.

Stomach cells are responsible for an acid production, as

age increases process of acid production slows down

Due to this transit time of food slows down

Leads to reflux of food from the oesophagus

Digestive enzymes can be used as digestive aid to help

absorb and digest food

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Digestive enzymes are proteins involved in the digestion of food. Found naturally in the body

and available in prescription form, digestive enzymes are also sold as dietary supplements.

Proponents claim that these over-the-counter enzymes can help treat a whole host of health

problems, including digestive issues like:

Celiac disease

Crohn's disease

Heartburn

Indigestion

Irritable bowel syndrome

Ulcerative colitis

Secreted mostly by the pancreas, digestive enzymes aid the body in breaking down fats,

proteins, and carbohydrates. When normal functioning of the pancreas is disrupted and causes

insufficient enzyme production, the body may be unable to properly absorb these nutrients.

Digestive enzyme supplements protect against this malabsorption, which can slow digestion

and lead to uncomfortable symptoms like bloating, flatulence, abdominal cramps, and

diarrhoea.

The digestive enzymes in supplements come from various sources, including animal

pancreases (pigs, cows, or lambs) or from plants. For instance, bromelain is derived from

pineapples, papain from papayas, and lactase from purified yeasts or fungi. Supplements also

often contain a mixture of enzymes, such as proteolytic enzymes like bromelain

and papain (needed to digest protein), lipase (needed to digest fat), and amylase (needed to

digest carbohydrates).

Although digestive enzymes supplements are normally taken with meals for digestive

purposes, when taken in between meals on an empty stomach, they promise to stimulate the

immune system, manage arthritis, reduce inflammation, improve liver health, fight cancer,

and more. Indeed, so much ado is being made about the purported benefits of digestive

enzymes that the global market for these supplements is expected to reach $1.6 billion by

2025.

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Health Benefits

1. Irritable Bowel Syndrome

A digestive enzyme known as pancrelipase may alleviate some symptoms of irritable bowel

syndrome (IBS). pancrelipase experienced a significantly greater improvement in such

symptoms as cramping, bloating, and pain.

2. Inflammatory Bowel Disease

bromelain may help manage colitis, or bowel inflammation. For example, a 2010 study

published in Inflammatory Bowel Diseases found that bromelain helped decrease

inflammation of the colon in mice with colitis.

Digestive enzymes may also be helpful in people with IBD who experience symptoms of

IBS, such as abdominal pain and diarrhoea, despite little or no active inflammation. This new

disorder is called IBD-IBS syndrome.

3. Cancer

Digestive enzymes have been reported to be beneficial to people undergoing cancer treatment

versus affecting the disease process itself, for instance by decreasing complications of

therapy.

4. Arthritis

bromelain may help relieve pain related to osteoarthritis (OA), likely due to its ability to

reduce inflammation.

5. Muscle Soreness

OTC enzymes in improving muscle soreness is mixed, and many studies are small and dated.

6. Autism

Digestive enzymes on children with ASD (autism spectrum disorders). had significant

improvement in emotional response, general behaviour, and gastrointestinal symptoms

(quality of stools, abdominal pain, vomiting, and food variety)

Possible Side Effects

Digestive enzymes may trigger a number of side effects, including stomach pain, nausea,

diarrhoea, and vomiting. In addition, some people may experience allergic reactions to

digestive enzymes.

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Bromelain, the enzyme from the pineapple, may have anti-platelet activity. If you take

blood thinners or have anti-platelet activity, taking it could possibly increase the risk of

bleeding.

Pregnant and lactating women are advised to consult their doctor before taking these

products.[29]

PUFAs

Fats are important for living organisms. Fatty acid (FA) are molecules having a variable

length carbon chain with a methyl terminus and a carboxylic acid head group. based on the

degree of saturation of their carbon chainsthey can be classified.

Saturated FAs possess the maximal number of hydrogen atoms

monounsaturated FAs and polyunsaturated FAs (PUFAs) have one, or two or more,

double bonds, respectively.

PUFAs can be further subdivided on the basis of the location of the first double bond

relative to the methyl terminus of the chain.

For example, n-3 and n-6 FAs are two of the most biologically significant PUFA classes, and

have their first double bond on either the third or sixth carbon from the chain terminus,

respectively. The final carbon in the FA chain is also known as the omega carbon, hence the

common reference to these FAs as omega-3 or omega-6 PUFAs.

Long-chain n-3 and n-6 PUFAs are synthesized from the essential FAs (EFAs) alpha-

linolenic acid (ALA) and linoleic acid, respectively. The typical Western diet provides n-6

and n-3 PUFAs in a ratio ranging from 8:1 to 25:1, values in severe contrast with the

recommendations from national health agencies of approximately 4:1.

Because most diets are already very rich in n-6 PUFAs, greater focus needs to be placed on

incorporating n-3 PUFAs into the diet. Dietary sources of n-3 PUFAs are readily available

but in limited quantities. Fatty fish, such as mackerel, herring and salmon, provide an

excellent source of the long-chain derivatives of ALA, eicosapentaenoic acid (EPA) and

docosahexaenoic acid (DHA).[30]

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Figure no 11: Classification of PUFAs.

Omega-3 [(n-3)] long-chain PUFA, including EPA and DHA, are dietary fats with an array of

health benefits.

They are incorporated in many parts of the body including cell membranes and play a role

in anti-inflammatory processes and in the viscosity of cell membranes.

EPA and DHA are essential for proper fetal development and healthy aging.

DHA is a key component of all cell membranes and is found in abundance in the brain

and retina.

EPA and DHA areprecursors of several metabolites that are potent lipid mediators, so

they are beneficial in the prevention or treatment of several diseases

PUFAs from obtained from Seafood sources such as fish and fish-oil supplements are the

primary contributors of the 2 biologically important dietary omega-3 fatty acids, EPA and

DHA.[31]

deficiency of dietary EPA and DHA is responsible for various conditions such as

increased inflammatory processes as well as poor fetal development, general cardiovascular

health, and risk of the development of Alzheimer's disease (AD).

LA accumulates in blood and tissue lipids with increasing intake, and this exacerbates

competition between LA and limited omega-3 fatty acids for metabolism and acylation into

tissue lipids.[32]

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