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Health effects of gamma linolenic acid, conjugated linoleic acid and herbal preparations.

An examination of the health effects of essential fatty add supplements, GLA, a novel fatty acid from linoleic add and certain significant herbal products.

There is a growing recognition by the health community of the importance of nutrition in health and disease. Rising costs of health care are forcing both governments and consumers to seek alternatives to traditional therapeutic care. Consumers are becoming much more interested in assuming more responsibility for their own health care and are concentrating upon the prevention, rather than the treatment of disease. In addition, more consumers are avoiding pharmaceutical remedies and turning to "natural" products. The aging of the "baby boomer" segment of the population is also creating a rapidly growing market for alternative health care products as these consumers become more familiar with the relationship between diet and disease. These events have led to increased interest in natural products and their role in optimal health.

Bioriginal Food and Science Corporation has responded to this growing need for alternative health care goods by providing our customers with high quality natural products grown and processed in Saskatchewan. Bioriginal supplies a number of companies which produce and sell health and nutrition products, cosmetics, veterinary and pet food products, over-the-counter products and pharmaceutical products. The main product lines for Bioriginal are specialty oils that are high in Essential Fatty Acids (EFAs). Examples are borage oil, evening primrose oil, flax seed oil and CLA (a new and unique fatty acid). We also market herbal and other natural plant products to a growing consumer market.

We believe that independently conducted clinical research is imperative to the credibility and commercial success of health and nutrition products. Bioriginal is a leader in EFA research, with particular focus upon Gamma Linolenic Acid (GLA). Each year we publish a thorough and unbiased Annotated Bibliography on all the GLA research conducted around the world. Currently, the edition contains close to 700 independent GLA studies. In addition, Bioriginal compiles thorough literature reviews on our other EFA supplements and herbal products to ensure that science supports our marketing efforts.

The Role of Science in the Health Food Industry

Clinical research over the past three decades has shown that a number of natural products may play an important role in the etiology of diseases including skin disorders, rheumatoid arthritis and diabetes mellitus. This article will focus upon the health effects of the essential fatty acid supplement, GLA from borage oil and evening primrose oil, the novel fatty acid conjugated linoleic acid and specific important herbal products.

Essential Fatty Acids

Essential nutrients cannot be produced by the body, yet are necessary for ideal health. There are over 50 such nutrients including the Essential Fatty Acids which must be supplied in the diet. EFA deficiency in experimental animals causes growth retardation, impaired fertility, fragility of red blood cells and skin lesions. Deficiency of EFA also depresses the reaction of the immune system to foreign substances and, thus, reduces the ability of the body to deal with infection.

EFAs serve several functions in the body. They are structural components of cell membranes and are therefore vital to cellular metabolism. EFAs are involved in communication between brain cells and are necessary for proper reception and transmission of nerve impulses.

The EFAs are also important as the starting point in the body for a group of very active, short-lived, hormone-like chemicals called "eicosanoids". Eicosanoids include prostaglandins (PGE), thromboxanes (TXB) and leukotrienes (LT). Each cell type produces its own form of eicosanoid to carry out its metabolic functions. Thus, eicosanoids are involved in numerous physiological activities including platelet aggregation (blood clotting), inflammation, haemorrhage, vasoconstriction and vasodilation, blood pressure, and immune function.

The Omega-6 and the Omega-3 EFA families form different eicosanoids with different activities [1]. A proper balance in the diet of EFA is important for the maintenance of good health as changes in the levels of EFA will have a profound effect on the production of eicosanoids by different cells and tissues, and hence on overall health.

Linoleic Acid, which is prevalent in the North American diet, is converted in the body to a longer chain EFA called arachidonic acid (AA) which is the starting point for the eicosanoids PGE2, TXB2 and LTB4. PGE2 causes inflammation and constriction of the blood vessels. TXB2 is also a powerful vasoconstrictor and also causes platelets to "clump" together or "aggregate". LTB4 is a potent pro-inflammatory agent.

The eicosanoids derived from GLA and from the omega 3 fatty acids like Alpha linolenic Acid (ALA) from flax oil and Eicopentanoic Acid (EPA) from fish oil have dramatically different effects in the body. These essential fatty acids are metabolized into eicosanoids which are anti-inflammatory and generally assist in reducing blood clotting.

Metabolism of GLA in Humans

GLA is then converted into an EFA called DGLA, which is converted to another group of important eicosanoids, PGE1 and 15 hydroxy-DGLA (15-OH-DGLA). Both of these compounds have significant anti-inflammatory and anti-aggregatory effects in the body [2]. DGLA also helps reduce the synthesis of the eicosanoids derived from AA (PGE2, TXB2 and LTB4) which, as indicated above, have negative properties.

GLA can be made in the body from LA, through the action of an enzyme called delta-6-desaturase (D6D). However, D6D, the enzyme that makes GLA (and, therefore, ensures adequate DGLA), is a "lazy" enzyme. Its activity can be reduced by high dietary consumption of alcohol, cholesterol, saturated fats (which are found in animal and dairy products), and trans fatty acids (which are produced in the manufacture of vegetable oil margarines and shortenings). Low dietary levels of some vitamins and minerals such as zinc, Vitamin B6, and magnesium can also reduce D6D activity as can genetic factors such as low insulin (diabetes), skin disorders and aging [3,4].

Therefore, direct dietary supplementation of GLA is often required to ensure that adequate levels of PGE1 and 15-OH DGLA are synthesized by the body. One way to ensure adequate GLA intake is to bypass the D6D enzyme and supply GLA directly through the diet.

Dietary Sources of Gamma Linolenic Acid (GLA)

The primary sources of GLA are plant oils; namely borage, evening primrose and black currant seed. Borage and evening primrose oils are the most popular of the GLA oils among consumers. Borage is a hardy annual or biennial plant native to Europe, North Africa and Asia where it has been grown primarily as an ornamental. Borage is now successfully cultivated in the Canadian prairies, specifically in Saskatchewan, where it thrives on warm days and cool nights. These growing conditions are ideal for high production of GLA in the seed oil. Bioriginal is the largest contract producer of borage in Saskatchewan.

Borage can be recognized by its bright blue flowers and the coarse, stiff, white prickly hairs which cover its surface. Borage leaves have traditionally been used in salads. Historically, herbalists have claimed that the consumption of borage leaves and flowers can treat depression and liver disorders. In addition, parts of the borage plant have diuretic characteristics which have encouraged its use for treating kidney and bladder inflammation.

The other primary source of GLA is the evening primrose plant which are native to North America. Evening primrose produces large yellow flowers with tiny seeds. Traditional use of evening primrose has included parts of the whole plant, externally to heal wounds and to soothe skin inflammation and internally to control coughs, as a sedative, pain killer and diuretic.

Within the last 20 years, borage oil and evening primrose oil (EPO) have been studied extensively as sources of GLA. Borage oil contains the highest level of GLA (22-25%), while EPO contains 8-10% GLA. Borage and EPO products have been granted Drug Identification Numbers by the Health Protection Branch of Health Canada in recognition of the health effects of GLA.

GLA supplementation is used for the production of PGE1 and 15-OH DGLA and to normalize the production of AA derived eicosanoids and, thus, control or cure several disease states.

Gamma Linolenic Acid and Skin Care

GLA and DGLA are important structural components of the upper skin (epidermal) layer which regulates moisture loss from the surface of the skin [5,6]. In the membranes surrounding the cells in the skin, GLA and DGLA help to provide a moisture barrier, stabilizing the membrane and helping to reduce water loss from the surface of the skin. The eicosanoids synthesized from AA, in particular PGE2 and LTB4, are involved in inflammatory reactions in the skin, and are in part responsible for the redness, pain, and intense itching common in such conditions as atopic dermatitis (AD), eczema and psoriasis in both children and adults [7]. In these conditions, levels of the AA derived eicosanoids have been found to be elevated [5]. PGE1, on the other hand, shows potent anti-inflammatory effects in the skin. PGE1 is also important for maintaining healthy skin by regulating water loss and protecting skin from injury and infection [6].

Oral Administration of Gamma Linolenic Acid-Containing Oils

Several recent studies in humans have indicated that orally administered borage oil increases tissue levels of PGE1 and 15-OH-DGLA and suppresses inflammation. Ziboh and Fletcher [8] reported that 1500 mg of borage oil per day for six weeks increased the DGLA content in blood cells by 130% and reduced levels of LTB4.

Borage oil in the form of the product Glandol, was administered to 12 patients with AD and compared to a palm oil placebo in order to evaluate changes in skin parameters [9]. Effects on the skin were measured by means of the Atopic Dermatitis Area and Severity Index (ADASI). The ADASI revealed that five out of seven patients treated with borage oil showed favourable improvements. In comparison, only one of five patients treated with the placebo showed any changes.

Oral administration of EPO have also yielded positive results. Stewart and co-workers [10] reported the treatment of severe and moderately severe atopic dermatitis with EPO in a multi-centre study. Thirteen dermatologists evaluated the clinical responses of 179 patients receiving 360 mg to 540 mg GLA daily (as EPO) for variable periods (3 to 5 months). The overall results were very positive, with 111 patients showing improvement within 12 weeks.

Topical Administration of Gamma Linolenic Acid-Containing Oils

Body creams containing borage oil have been found to be superior to regular hand cream in restoring moisture and smoothness to do', scaly skin when tested for 14 days on the forearms of 20 healthy subjects [ 11 ]. Results indicated that the borage oil cream reduced TEWL which further enhanced moisture levels in the treated skin.

Infantile seborrhoeic dermatitis (ISD), a common condition in infants also known as "cradle cap", has successfully been treated with borage oil. ISD is characterized by dry or moist greasy scales and yellowish crusts on the scalp, eyelids, face, outer surfaces of the ears, armpits, breasts, groin and gluteal folds. In a recent study [12], 48 children with ISD received topical applications of borage oil (0.5 ml) twice daily. Skin lesions cleared up within 10 to 12 days following treatment. Symptoms reappeared within one week when the borage oil treatment was discontinued. The authors hypothesized that immature functioning of the D6D enzyme may be responsible for ISD in this population and can be corrected with GLA in the form of borage oil.

As a result of these positive findings, an EPO product was licensed in the United Kingdom in 1989 as a prescription drug for the symptomatic relief of atopic eczema. Under specific regulations of the Japanese Ministry of Health and Welfare contained in the document Foods for Specified Health Use, claims for the use of GLA containing oils for the treatment of atopic eczema have been approved. Food products that contain GLA can be registered as "foods with medicinal properties" in Japan. In addition, beneficial health claims are allowed for GLA in the area of blood cholesterol lowering.

Borage oil from Bioriginal is used in several skin care products in the United States including the Dermasil and Vaseline skin care lines marketed by Chesebrough Ponds. Borage oil is also used in several Estee Lauder products.

Gamma Linolenic Acid and Rheumatoid arthritis

Rheumatoid arthritis affects as many as 37 million, or one in seven, individuals in North America, making it one of the more common chronic diseases [13]. Conventional arthritis therapy treats the condition, but does not cure it. Treatments used in rheumatoid arthritis usually include anti-inflammatory drugs and corticosteroids which can lead to kidney and liver damage and gastrointestinal problems. Recent research has shown borage oil to be a safer, non-invasive treatment for inflammation.

The administration of 1.1 g/day of GLA from borage oil (9 capsules/day) for 12 weeks significantly suppressed the production of the pro-inflammatory compounds PGE2, TXB2 and LTB4 in seven normal subjects and in seven patients with active rheumatoid arthritis [14]. In six of the seven patients, improvements in sleep patterns, joint scores, morning stiffness and the patient's overall assessment of disease activity were noted. The authors postulated that the positive effects of borage oil were due to a reduction in the synthesis of AA derived eicosanoids. In a study by Leventhal and co-workers [15], borage oil supplementation to provide 1.4 g/day of GLA improved active rheumatoid arthritis in 14 patients treated i for 24 weeks. These patients showed significant reductions of 36% in joint tenderness, of 45% in tender joint score, of 28% in swollen joint count, of 41% in swollen joint score and of 33% in morning stiffness. In 13 patients receiving the placebo, all clinical measures worsened. The researchers concluded that GLA administration from borage oil appears to be a worthwhile strategy for the treatment of chronic synovitis associated with active rheumatoid arthritis. in both of the latter studies, the borage oil supplements were well tolerated and no adverse effects were reported by the subjects.

The overall results of clinical trials with GLA in the form of borage oil support the continued investigation of this oil as a possible therapeutic agent for the treatment of rheumatoid arthritis. For less severe inflammation, lower dosages of borage oil appear to be effective in reducing joint tenderness and swelling, safe and without side-effects. Borage oil appears to be the preferred oil of choice for GLA supplementation due to its higher concentrations of the EFA which allows for larger amounts of GLA to be incorporated into the diet without the necessity of high oil consumption.

Gamma Linolenic Acid and Diabetic Neuropathy

GLA has been found to be effective in reducing symptoms of diabetic neuropathy, a common complication of both insulin-dependent and non-insulin-dependent diabetes mellitus. Diabetics have been shown to require higher amounts of EFAs, specifically GLA, because of impairments in D6D activity, which result in reductions in both GLA and DGLA levels in cell membranes [16].

DGLA is a major constituent of nerve cells and is required for normal neuronal cell membrane structure, normal regulation of nerve conduction, and for the release of eicosanoids involved in nerve microcirculation. Diabetic neuropathy, a common complication of both insulin-dependent and non-insulin-dependent diabetes mellitus, is a condition where nerves degenerate and symptoms of pain and numbness follow [17]. It has been reported to occur in 95% of diabetics with 50% showing clinical symptoms. It can lead to skin ulceration, muscle weakness, cardiovascular problems and impotence. Diabetic neuropathy is the most common reason for leg amputation in many Western countries. In the USA, 20,000 amputations occur yearly as a result of this condition.

The effects of GLA on the prevention and treatment of diabetic neuropathy has been extensively studied. In an early study by Jamal and Carmicheal [18], patients receiving 360 mg GLA in the form of EPO showed statistically significant improvement in a number of parameters of neuropathy over the placebo control group.

Keen and co-workers [19] confirmed the positive effects of GLA on diabetic neuropathy in a study in which 84 patients received GLA (480 mg/day as 12 capsules of EPO) for one year in randomized, double-blind, placebo-controlled parallel design. Sixteen parameters (neurophysical, neurological and biochemical) were evaluated quarterly. For all 16 parameters, the change over one year in response to GLA was more favourable than the change with placebo. The authors concluded that GLA had a beneficial effect on the course of diabetic neuropathy, was not associated with important adverse events and may offer an advance in the management of diabetic neuropathy.

In light of the beneficial effects of GLA on human diabetic neuropathy, Horrobin [17] conducted a large scale trial involving 400 patients supplemented with 480 mg/ day GLA in the form of 6 g of EPO/day. It was reported that GLA supplementation improved a number of parameters of neuropathophysiology. Clinical measurements of thermal threshold also improved. These improvements increased over time from 3 to 12 months. In contrast, in the placebo treated group, all parameters were negatively affected. After treatment was continued for a second year, further improvements were noted in the GLA treated patients. The mechanism responsible for the positive effects of GLA may be due to a restoration of normal nerve conduction velocity.

How Much GLA Should We Consume?

The recommended level of GLA for normal nutritional supplementation is between 150 to 300 mg/day. Amounts of 500 mg/day may be required in some situations, for example, in a diet high in cholesterol and saturated fatty, acids. Even higher levels may be necessary for the treatment of specific disease symptoms upon the advice of a physician.

What Type of GLA Supplements Should Consumers Choose?

High quality GLA supplements are absolutely essential for optimum bioavailability and function in the body. Consistency in quality testing is very important in this regard. Bioriginal has the most complete quality specifications for EFA supplements in the world. Bioriginal's GLA products are processed by expeller pressing (a non-polluting method that avoids gasoline-like hexane residues). Bioriginal was also the first GLA supplier to join the National Nutritional Foods Association Tru-Label assurance program and the first GLA supplier to guarantee that all of its GLA products adhere to the CODEX standards for edible oil safety established by the World Health Organization.

A New Fatty Acid Supplement - Conjugated Linoleic Acid

Conjugated linoleic acid (CLA) is a collective term given to positional and geometric isomers of linoleic acid (LA) CLA and LA are both 18 carbon FA with two double bonds. The two FAs differ in the position of their double bonds. The unique chemistry of CLA results in very different biological and health properties than LA.

Dietary CLA has been studied since the 1940s. Bioriginal has compiled an extensive uses literature review on the health effects of CLA which includes over 50 studies conducted since 1978, on the metabolic and physiological effects of this unique FA.

CLA and Cancer

CLA has been found to be more powerful than any other fatty acid in modulating tumor development in various types of cancer [20]. The cancer-lowering effects of CLA have been reported in skin cancer tumors [21]. in this study, CLA-treated mice developed only one-half the number of tumor cells and exhibited an overall lower tumor incidence in comparison to animals not treated with CLA [21 ]. CLA has also been found to inhibit tumor initiation of mouse forestomach carcinogenesis [22]. Mice treated with CLA developed only hall as many tumors as did animals not supplemented with CLA.

In studies examining mammary carcinogenesis, CLA was found to express a dose-dependent inhibitory effect on tumors in rats [20]. Cell culture experiments using human cell lines supports the anticarcinogenic properties of CLA that have been observed in animal research. Shultz and co-workers [23,24] reported that CLA. suppressed colorectal cancer, melanoma and breast cancer proliferation from 18 to 100% depending on cell type. Within one week, cancer cell growth was reduced by one-half in a number of cancer cell cultures. In this particular research, human breast cancer cells were found to be most responsive.

CLA and Coronary Heart Disease

CLA has recently been reported to be a powerful agent in reducing blood cholesterol levels [27]. Feeding CLA to hamsters significantly reduced total and non-HDL (good) cholesterol levels by 20% and 32%, respectively, in comparison to animals fed diets rich in LA. In the same study, aortic fatty streak formation, the first stage in the development of an atherosclerotic plaque, was significantly reduced by 45% in the animals fed CLA.

CLA and its Antioxidant Properties

There is considerable scientific evidence that free radical-mediated oxidation in the body play a role in the onset of cancer and atherosclerosis. CLA appears to have powerful antioxidant properties which can be beneficial in reducing cancer cell generation and the formation of atherosclerotic plaques [20]. CLA-enriched membranes have been shown to be much more resistant to oxidation than microsomes from animals not treated with CLA [21].

How much CLA Should We Consume?

Human studies to confirm the positive effects of CLA as observed in animal models are currently underway. The recommended dietary intake of CLA has been extrapolated from animal studies and found to be approximately 3.5 grams per day [28].

The Exciting World of Herbs

New herbal products are appearing on the market and their popularity is increasingly being supported by clinical research studies. Feverfew, Echinacea, and Valerian have numerous health benefits which are being exploited by the medical community and by consumers.

Feverfew (Chrysanthemum parthenium) is an aromatic plant with a strong and lasting odour. Feverfew has been studied most extensively for its effects on migraine headaches. in an early, study, Johnson and co-workers [29] reported that approximately 60 mg of feverfew in capsule form, consumed by regular feverfew users, prevented the onset of migraines. The incidence of nausea and vomiting were also reduced in these individuals. These results were repeated by Murphy and co-workers [30] who studied the effects of approximately 82 mg of feverfew on migraine incidence in 30 volunteers. The randomized double-blind placebo-controlled assessment period lasted for four-months. Treatment with feverfew was associated with a reduction in the number and severity of migraines as well as the degree of vomiting. No serious side-effects were reported. "These effects have been attributed to an active ingredient in feverfew called parthenolide.

The herb is also used externally as an insect repellent and for treating insect bites. Herbalists have traditionally recommended feverfew to reduce fevers. More recently, the herbal product has been used as a treatment for disorders including menstrual cramps, muscle aches, nausea, asthma and inflammation.

Numerous studies have focused upon the health effects of several members of the Echinacea family, the two most common being Echinacea purpurea and Echinacea angustifolia. Echinacea is a native North American plant belonging to the daisy family. The flowers are distinguished by their narrow-petaled purple cones. The herb has a long history of use, especially by native Indian tribes. Traditionally, Echinacea roots and leaves were used to treat sore throats, fever, flu, allergies, asthma, eczema, acne, poison ivy and as a digestive aid and diuretic. However, most research has been directed to the effectiveness of Echinacea in strengthening the immune system, specifically as a treatment for cold and flu symptoms especially when aggravated by congestive nasal and respiratory distress. in a German study conducted in 180 men and women ranging in age from 18 to 60, 450 mg or 900 mg of Echinacea purpurea taken as a tincture, was effective in clinically relieving the symptoms and duration of flu-like symptoms [31]. The effects of the higher dose were more dramatic with results apparent after 3-4 days and full effectiveness being reported following 8-10 days. In another study, 108 patients with colds received either an extract of the fresh-pressed juice of Echinacea purpurea (4 ml twice daily) or a placebo for 8 weeks [32]. The results showed that 35.2% of the group receiving Echinacea purpurea remained healthy throughout the study while only 25.9% of the patients taking the placebo exhibiting similar effects. The length of time between infections was increased to 40 days in those individuals treated with Echinacea purpurea compared to 25 days in the group taking the placebo. When infection did develop in the patients receiving Echinacea purpurea, the symptoms were much less severe than in the placebo group. Several other studies have reported similar results.

Echinacea roots and leaves contain polysaccharide compounds known as arabinogalactans which are believed to be in part responsible for immunostimulating effects. Clinically, Echinacea has been reported to enhance the ability of white blood cells to move into areas of infection which assists in reducing both bacterial and vital infections [33]. in addition, Echinacea has been shown to elevate serum white blood cell counts when they are low and to activate these cells, especially T-lymphocytes, macrophages and natural killer cells [34]. Effects on natural killer cells are especially important as these cells are the body's first line of defence against viral infection.

Another herbal product that is attracting interest in the health area is valerian (Valeriana officinalis). The plant grows in a number of different environments and is cultivated in North America having originated from Europe. Valerian has a long history of use in Europe and is still very popular. Over one half dozen Valeriania species are reported to have been used by native indian tribes in North America to treat colds, promote wound healing, and cure headaches [35]. The plant produces tuberous roots which contain alkaloid compounds, in particular valepotriate. Several reports indicate that valerian in moderate doses can produce a calming effect as it acts as mild central nervous system depressant and muscle relaxant [36]. When taken internally, valerian has a sedative effect and may be beneficial to reduce restlessness and nervousness. Herbalists support the use of valerian as a hypotensive agent and as an antispasmodic compound in some clinical cases.

Based upon the growing momentum in clinical research in the area of GLA, CLA and herbal preparations, there will continue to be a greater awareness of the nutritional value of specific novel natural food products.. As the research community, health care professionals, retailers and consumers gain in their understanding of the nutritional value of these unique compounds increases, their popularity will grow. the development of the alternative health care products continues to look more and more positive for consumers.


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36. Krieglstein, J. and Grusla, D., 'Central Depressant Constituent in Valeriana', Deut. Apoth. Zeit., 128:2041, 1988.

Rick Kulow is the President and founder of Bioriginal Foods Inc.
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Author:Kulow, Rick
Publication:Canadian Chemical News
Date:Nov 1, 1997
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