NUTRACEUTICALS / NUTRACEUTICS

  Compiled by Suwaldi Martodihardjo

The term of nutraceutical was first used by Stephen DeFelice in 1991.  Definition of Nutraceutical(s): Any substance that may be considered a food or a part of a food and provides medical or health benefits, including the prevention and treatment of disease According to Mueller and Nestle (1995), “NUTRACEUTICALS” include:Conventional Foods (labeling regulated under NLEA, Nutrition Labeling & Education Act, of 1990) - Conventional foods - Functional foods - Phytochemicals

Foods for Special Dietary Uses (FSDU) (labeling regulated under NLEA, Nutrition Labeling & Education Act, of 1990)

- Hypoallergenic foods - Weight reduction foods - Diabetics’ foods - Reduced sodium foods - Infant formulas

Dietary Supplements (Labeling Regulated Under DSHEA, Dietary Supplement Health and Education Act of 1994)

- Essential nutrients . Vitamins . Minerals . Amino acids - Herbal preparations - Glandular extracts

Medical Foods (Exempt from most NLEA and DSHEA Labeling Requirements)

- Fall under narrower scope than FSDU - Primarily includes products for those with inborn errors of metabolism

Supplements: Supplements could be considered additives because

they become part of the diet even when they are not in a food product. A food additive is any substance that becomes part of a food product.

Broad purposes of food additives include: → maintaining or improving nutritional value such as the

addition of vitamins and minerals to a food products (addition of calcium to juices and other foods)

→to maintain freshness in the food (addition of antioxidants to foods processed with fat and of preservatives help to prevent spoilage)

→to help in the processing and preparation of foods such as emulsifiers are added to peanut butter and mayonnaise to keep the product smooth

→to make food more appealing (addition of coloring agents, synthetic flavors, and sweeteners)

Dietary Supplements: Dietary Supplement Health and Education Act (DSHEA), 1994

‘Any product (other than tobacco) intended to supplement the diet that contains one or more of the following ingredients: a vitamin, mineral, herb or other botanical, an amino acid; a concentrate, metabolite, constituent, extract or combination of any of these ingredients’

‘A supplement must be in “dosage forms such as capsules, tablets, liquids, powders, or soft gels and may not be represented as a conventional food or as a sole item of a meal or of the diet”

In addition, dietary supplements must be labeled as supplements.

Dietary supplements are permitted to carry disease claims for the following:

Folic acid and decreased risk of neural defects

Calcium and a lower risk of osteoporosis

Psyllium seed husk and heart disease Soy protein and heart disease Omega-3 fatty acids and heart disease B vitamins (folic acid, B6, and B12) and

heart disease

The antioxidants, vitamin A, C, and E, are among the most commonly known nutrients which, in general, may be useful in the prevention of cancer and cerebrovascular disease.

The combination of vitamin E, C, and beta-carotene has been useful in reducing LDL oxidation and subsequent atherosclerosis.

Jialal and Fuller (1995, Effect of Vitamin E, Vitamin C and beta-carotene on LDL oxidation and atherosclerosis, Can. J. Cardiol., 11, 97G-103G) speculated that the combination of vitamin E, C, and beta-carotene work synergistically to prevent oxidation of LDL in the following manner:

→ Vitamin C scavenges aqueous radicals and regenerates alpha-tocopherol from the tocopheroxyl radical species;

→Vitamin E, in the form of alpha-tocopherol protects polyunsaturated fatty acids within the LDL particle, reduces platelet adhesion and inhibits smooth muscle cell proliferation and protein kinase C activity; and

→Beta-carotene provides reserve antioxidant activity, especially in the arterial wall where low partial pressures of oxygen are found.

Supplementation with vitamin C may be beneficial in the management of asthma patients, and high dietary intake of vitamin E may prevent Parkinson’s disease

NUTRACEUTICALS FOR EYE HEALTH Sunlight exposure has been linked to premature vision loss, development

of cataracts, and increased risk of age-related macular degeneration (ARMD) – leading cause of blindness in people over sixty-five years of age.

With regard to cataract development, with age, virtually everybody will develop some degree of oxidative damage to the lenses of their eyes (the first step in cataract development)

The macula is a specialized region in the back of the eye (retina) that allows you to see fine details.

As cells in the macula region begin to break down, the eyes begin to lose sight in the center of the field of vision and may develop problems seeing in bright or dark conditions.

Factors have been identified as risk factors for ARMD: 1. sunlight exposure 6. genetic 2. age 7. female 3. smoking 8. high saturated fat intake 4. diet 9. hypertension 5. low antioxidant level 10. low macular pigment density

A cataract is a clouding of the crystalline lens (clear tissue behind the pupil) that causes a gradual loss of vision.

Etiology Aging is the most common cause of cataracts; in fact, most patients

over 50 years of age demonstrate cataractous changes. However cataracts may also be congenital, hereditary, or associated with systemic, metabolic, or ocular diseases, trauma, radiation, maternal infection during pregnancy, electrical injuries, and drug use.

Risk Factors Age over 50 years Genetic diseases (e.g., myotonic dystrophy, neurofibromatosis type

2, Lowe syndrome, Down syndrome) Drug therapy (e.g., miotics, steroids, phenothiazines) Maternal infection (e.g., rubella, cytomegalovirus), drug ingestion,

or radiation therapy during pregnancy Metabolic disorders (e.g., diabetes mellitus, galactosemia,

hypocalcemia) Ocular disorders (e.g., glaucoma, uveitis, retinal detachment,

trauma) High-voltage electrical injury

Signs and Symptoms Decreased or blurred vision (often described as a "fog") Double vision Colored halo around lights Increased refractive power of lens, allowing patients to read without

glasses (i.e., second sight) Brown spots in the visual field

Drug Therapies Some studies have suggested that high-dose aspirin therapy given

for other causes (e.g., arthritis) is associated with a decreased incidence of senile cataract; however, most of the evidence is speculative.

Eye drops (e.g., phenylephrine [Neo- Synephrine, 2.5%], homatropine, 2%), to dilate the pupil to provide better vision in patients with nuclear sclerotic or posterior subcapsular cataract

Aldose reductase inhibitors, to prevent conversion of sugars to polyols in galactosemic or diabetic patients, thereby preventing or delaying cataract formation

Prophylactic antibiotics for three weeks following cataract extraction Steroid eye drops three to six weeks following cataract extraction

Nutritional and herbal therapies help prevent and minimize the progression of cataract formation. Correcting underlying nutritional deficiencies and addressing contributing factors, such as diabetes, is essential to treatment.

Nutrition /Nutraceuticals Increase dietary antioxidants which may protect against free radical

damage to the eye, especially dark leafy greens and orange and yellow vegetables. Dark berries, particularly blueberries, are rich in flavonoids, which may be protective to the lens.

Vitamin C (500 to 1,000 mg bid to tid) is found at high concentrations in the lens of the eye and has antioxidant activity.

Glutathione is highly concentrated in the lens and protects against UV light. Supplementing with glutathionine (200 mg bid) or its amino acid precursors (L-cysteine 200 mg bid, L- glycine 100 mg bid, and L-glutamine 100 mg bid) may be beneficial.

Selenium (200 mcg/day) is a co-factor for glutathionine peroxidase which helps keep glutathionine in its active state.

Vitamin E (400 IU/day) protects against free radical damage. Zinc (15 to 30 mg/day) deficiency may contribute to cataract formation,

especially with impaired glucose metabolism occurring with diabetes or age.

Vitamin A (10,000 IU/day) and beta-carotene (50,000 IU daily) are antioxidants that protect against light-induced damage to the eye.

In terms of diet, individuals who consume fruits and vegetables at least once per day have significantly reduced risk of developing ARMD and cataracts.

Among the dietary antioxidants, carotenoids appear to provide the greatest benefit – two carotenoids in particulars, lutein and zeaxanthin – seem to be the most effective

LUTEIN and ZEAXANTHIN Lutein and zeaxanthin are yellow pigments found in high

concentration in yellow fruits and vegetables as well as in dark green, leafy vegetables such as spinach, broccoli, kale, and collard greens. Egg yolk, corn, orange juice, honey dew melon and orange pepper are also good sources of lutein and zeaxanthin.

Individuals who consume a lot of spinach reduce their risk of developing ARMD by almost 90%.

Lutein and zeaxanthin end up concentrated specifically in the eye

(in the macular region of the retina). High levels of these carotenoids in the eye serve to protect tissues by minimizing free radical damage and by absorbing damaging blue light rays.

Lutein and zeaxanthin are the only carotenoids in the lens.

Lutein and zeaxanthin are able to quench singlet oxygen, a highly reactive free radical that can damage deoxyribonucleic acid (DNA).

Lutein and zeaxanthin are even more effective at preventing lipid peroxidation, and are themselves better protected against secondary oxidative breakdown when melatonin, glutathione, alpha-tocopherol and ascorbate are also present.

Lutein and zeaxanthin are better antioxidants than hydrocarbon carotenoids, such as beta-carotene because lutein and zeaxanthin undergo a 2e-oxidation of hydroxyl groups as opposed to the 1e- oxidation of hydrocarbon carotenoids.

UV light is filtered by the cornea and lens in the anterior aspect of the eye but visible light reaches the retina. Visible light in the blue spectrum is the most damaging. The short wavelength (400-500 nm) is 30 times more damaging than long wavelength light (510-749 nm). Macular pigment absorbs blue light as it enters the inner retinal layers, reducing the amount reaching the fovea. This reduces the potential for photo-oxidation of reactive saturated lipids of photoreceptors.

In people with normal amount s of macular pigment, 20%-40% of light at 460 nm is absorbed and up to 90% can be absorbed in the higher than normal amounts of macular pigment. There is a high degree of individual variability in concentration of lutein and zeaxanthin in the fovea.

In the cells, lutein and zeaxanthin may selectively bind to tubulin, a structural protein necessary in the formation of the cytoskeleton within axons. This could improve structural integrity and function of the cytoskeleton, thus helping maintain eye health and quality of vision the improvements in vision, such as higher contrast sensitivity, less glare, and improved color perception.

The normal range of concentrations of lutein and zeaxanthin in serum is between 0.08 and 0.35 mg/ml. Their serum half-life is around one to two weeks.

There are a number of other nutraceuticals that might have beneficial effects regarding vision and the eye: astaxanthin, pycnogenol, DHA, and ALA,

Some antioxidants vitamins may have beneficial effects in protecting delicate structures from damage as well as promoting repair processes by supporting collagen synthesis; these vitamins are vitamin C, vitamin E, bioflavonoids, beta-carotene, cysteine, and alpha lipoic acid.

Vitamin C levels in the eye decrease with age – a situation that can reduce capillary integrity and increase the risk of cataracts.

One of the major antioxidant enzymes in the eye is glutathione The synthesis of glutathione can be stimulated by a combination of

cysteine, alpha-lipoic acid, vitamin C, and vitamin E. Vitamin B2 and B3 (niacin) are useful support nutrients to help

maintaining glutathione synthesis

Bioflavonoids are known to act as powerful antioxidants to help protect the lens of the eye as well as strengthen the collagen-containing structures of the eye such as the cornea and capillaries.

Bioflavonoids typically found in blueberries, bilberries, red or purple grapes, citrus fruits, and cranberries.

Quercetin is one flavonoid which can help inhibiting accumulation of sugar alcohols such as sorbitol in the eye of diabetics.

NUTRACEUTICALS FOR EYE HEALTH Ingredients

Dose (per day)

Primary claims / Notes

Alpha-lipoic acid 100-300 mg Glutathione support, can be boosted with added cysteine

Beta-carotene 5 – 6 mg Best as part of a mixed carotenoid blend

Bilberry 100–500 mg Promotes better night vision – look for anthocyanoside content of 25 % or more

Bioflavonoids 100-300 mg Look for anthocyanidin and/or polyphenol content

Ginkgo biloba 60-120 mg Look for “24/6” 24% flavone glycosides 6% terpene lactones

Grape seed extract

50-100 mg General antioxidant benefits

Lutein/zeaxanthin 3-6 mg Good antioxidants

Ingredient Dose (per day)

Primary claims/ Notes

N- Acetylcysteine (NAC)

250-1500 mg General antioxidant benefit, increases cellular glutathione levels

Quercetin 50-100 mg General antioxidant benefits

Selenium 70-200 mcgVitamin C 200-1000 mg Collagen support

Vitamin E 100-800 IU Look for natural source d-alpha-tocopherol versus synthetic dl-form

KEY POINTS REGARDING DIETARY SUPPLEMENTS FOR EYE HEALTH

ARMD is the leading cause of blindness in people over age 65 ARMD affects 25-40% of all people over 65, in the USA Females have higher risk of ARMD than males People with light-colored eyes have an increased risk of ARMD ARMD and cataract risk are both related to total sunlight

exposure, cigarette smoking, and dietary intake of antioxidants

Antioxidant-rich fruits and vegetables are linked with lower rates of ARMD and cataracts

Among antioxidant nutrients, the carotenoids lutein and zeaxanthin, appear to be the most effective in directly protecting eye health, while other antioxidant-nutrients, such as bioflavonoids, cysteine, alpha-lipoic acid, beta-carotene, and vitamin C and E, can provide additional support

Lutein and zeaxanthin are the only carotenoids that concentrate specifically in the eye tissue

In the macula region of the eye, lutein and zeaxanthin serve to protect eye tissues from free radical damage and from photo-oxidizing damage of light rays

RELAXATION EFFECTS OF TEA L- THEANINE

In modern society, people are prone to several kinds of stress and stress-induced diseases.

Stress is classified into physicochemical stress, physiological stress, and psychological stress.

Physicochemical stresses are caused by cold, heat, injury, buzz, exhaust fumes, and so on.

Physiological stresses are the result of starvation, infection, overwork, and so on.

Psychological stresses arise from anxiety, strain, dissatisfaction, disappointment, anger, and other emotions.

Stressful events induce both psychological and physical hypertension, which can lead to diseases such as duodenal ulcer, depression, sleeplessness, and autonomic imbalance.

The significance of the correlation between health and stress is increasing, and therefore, relaxation techniques for stress reduction are important.

Relaxation methods can calm down the overly tensed organism and prevent stress-induced diseases.

Mental and physical health is maintained and promoted by acquiring the habit of relaxation, which induces two essential elements, physical and psychological relaxed states.

Mental state of relaxation can be recognized by observing such parameters as oxygen consumption, carbon dioxide elimination, heart rate, respiratory rate, minute ventilation, and arterial blood lactate.

In the relaxed state, blood pressure (systolic, diastolic, and mean blood pressure) and renal temperature do not change, while skin resistance markedly increases and skeletal muscle blood flow slightly increases.

The electroencephalogram (EEG) demonstrates an increase in the intensity of slow α-waves occasionally some θ -waves activity.

These changes are consistent with generalized decreased sympathetic nervous system activity and are distinctly different from the physiological changes noted when a person is sitting quietly or sleeping.

Relaxation methods should be effective to induce the above conditions for proper relaxation.

Food factors help relieve stress and induce a feeling of relaxation. For example, drinking tea for relaxation is common in many parts of the world. In Japan, the tradition of drinking green tea is considered beneficial for stress relief and general well being.

The functional substance in green tea that promotes relaxation is L-theanine, an amino acid abundant in green tea leaves (1 to 2% in dry weight),

It has been recognized that L- theanine is as being responsible for creating a feeling of relaxation and for promoting brain health.

L-Theanine exists in free (non-protein) form, and it is the predominant amino acid (about 50%) of the total free amino acids in green tea leaves.

Brain waves, the very weak electrical pulses from the brain surface, are an index for mental condition. Depending on the electrical frequency, the waves are classified as α, β, δ and θ -waves, which represent relaxation, excitation, sound sleep, and doze sleep, respectively.

The presence of L- theanine in tea leaves was discovered in 1949. Its chemical structure was determined as gamma- ethylamino -L-glutamic acid (L- theanine).

High-quality teas, such as maccha and gyokuro, contain a higher amount of amino acids as well as L- theanine than do inferior ones (bancha).

Suntheanine® is the trade name of L-theanine manufactured by Taiyo Kagaku Co., Ltd.

The study of the relaxation effects of Suntheanine® both in animal and human models and proved that Suntheanine® promotes psychological relaxation by inducing brain waves and suppressing the sympathetic nervous system and promotes physiological relaxation by relieving the effects of premenstrual syndrome (PMS).

KEY POINTS REGARDING THE RELAXATION EFFECTS OF TEA L-THEANINE In modern times, stress has become the root cause of many

abnormalities in our metal and physical conditions.

The state of relaxation is a basic requirement not only to relieve stress but also its side effects. In Japan, drinking green tea for relaxation has been customary from ancient times.

Research on green tea has revealed that L-theanine, an abundant amino acid found in green tea leaves, can bring about a state of relaxation.

L-Theanine commercially sold as Suntheanine® has been shown to induce both psychological and physiological relaxation.

Suntheanine® induces strong α-waves in the brain, which clearly indicates its psychological relaxation effects in humans. Suntheanine® has also been found to alleviate the symptoms of PMS and reduce caffeine-induced excitation as well as blood pressure in hyperactivity by suppressing the central nervous system.

Suntheanine® is safe, and no dietary limits have been imposed in Japan. Based on various studies, Suntheanine® has been widely recommended for various food applications, which target relaxation. Suntheanine® tablets (50 mg /tablet) are convenient to use and highly effective.

CONCLUDING REMARK THANK YOU FOR PAYING ATTENTION

HOPEFULLY, THIS PRESENTATION MAY BROADEN OUR KNOWLEDGE

NUTRACEUTICS IS IMPORTANT TO BE DEVELOPED AT THE FACULTY OF PHARMACY GMU