Information and Betalains (Technical)

The constantly increasing demand of natural food products is associated with the pronounced request for natural ingredients and supplements to prevent or treat disease. The multiple functional properties of cactus pear fit well this trend.

In this article, we describe the multiple functional properties of cactus pear juice and the beneficial influence in prevention or treatment of inflammatory disease like Rheumatoid arthritis and Osteoarthritis (OA). The Nopal cactus pear juice contains high antioxidant capacity in vitro of Betalins, especially for superoxide and peroxyl scavenging, which decrees inflammation and rescue cells under attack by the free radicals, therefore increasing the fruits possible health benefits.

Betalains act to clean up the dead cells and help to prevent them from becoming a target for disease and was found to be a potential cyclooxygenase (COX)-1 and COX-2 inhibitor. It also showed a weak effect on lipopolysaccharide (LPS)-induced nitric oxide but no effect on either lymphocyte proliferation or phagocytic capacity.

Several studies in research related the importance of diets and use of supplements in the prevention of inflammatory disease like Rheumatoid arthritis and Osteoarthritis (OA), a common type of arthritis with increased number in the aging population.

Rheumatoid arthritis (RA) often dismissed as joint aches associated with aging, is a chronic disease mainly characterized by inflammation of the synovial membrane of the joints causing pain, warmth, stiffness, redness and swelling around the joint. As the disease progress to chronic stages, the growth of a pannus covering the synovial membrane causes the membrane to be thickened. This process is mediated by production of various cytokines, for example, tumor necrosis factor (TNF- ) and interleukin 1 (IL-1) by antigen-presenting cells and T cells.

The inflamed cells release enzymes that may digest bone and cartilage, often causing the involved joint to lose its shape, alignment, and loss of movement. Intra-articular loose bodies may develop as a consequence of the inflammatory process, thus perpetuating the inflammation themselves. Hyperemia is the first step in the inflammatory cascade. It is a hallmark of acute inflammation and is also seen in exacerbation of chronic disease. This process is reversible. As the inflammation goes on, an infiltration by inflammatory cells is noted. As long as there is no fibrosis and no cartilage or bone destruction, it is to be assumed that the process might be fully reversible. Lymphatic tissue organizes. A spectrum of cytokines and proteases is excreted, causing destruction of cartilage and bone. Because it is a chronic disease, RA continues indefinitely and may not go away.

Many publications list the many benefits of taking supplements for the prevention of inflammation, hypertension, cancer, and the importance of proper diet and supplements during treatments. (Bruera, Strasser, Palmer, Wiley, Calder et al., 2003; Norman, Butrum, Feldman, Heber, Nixon et al., 2003; Bauer & Capra, 2004).

Background:
A high intake of fruits and vegetables was found to be positively associated with a lower chance of many diseases in epidemiological studies and clinical trials linked to the every day damage caused by free radicals.
The free radicals are constantly formed as byproducts of aerobic metabolism in the human body (Davies, K. J. A). These are molecules or atoms with unpaired electrons; they are generally reactive oxygen or nitrogen species (ROS or RNS). The most common are superoxide, peroxyl radical, nitric oxide (NO), and peroxynitrite (ONOO-).

These free radicals have been associated with many chronic and degenerative diseases including, inflammatory disease, vascular diseases, diabetes, cancer, and overall aging.

The body has developed a number of mechanisms to minimize free radical damage and even repair damage. Enzymes such as superoxide dismutase, catalase, and glutathione reductase, as well as antioxidants such as vitamin A, vitamin C, vitamin E, and polyphenols play important roles in protecting the body from free radical damage. Superoxide dismutase (SOD) is present in both the mitochondria and the cytosol. Hydrogen peroxide can be easily transformed into the dangerous hydroxyl radical via reaction with Fe2+. Catalase reacts with hydrogen peroxide to form water and oxygen. Glutathione peroxidase can also react with hydrogen peroxide, by reducing hydrogen peroxide and oxidizing glutathione but all these physiological protective mechanisms are still not protecting has from developing disease.

Dietary antioxidants are believed to be good external sources for protection, working in synergism with the free radical defense mechanism along with the enzymatic processes in the body.

Nitric oxide (NO) is an inorganic free radical that functions as an intracellular messenger and effector molecule. It is produced during the conversion of arginine to citrulline and its production is catalyzed by the enzyme nitric oxide synthase (NOS) (Knowles, R. G).

NOS has three isoforms: NOS I, II, and III. Out of these three isoforms, only NOS II is inducible and is produced during macrophage activation. Macrophage activation is thus accompanied by the induction of inducible nitric oxide synthase and sustained release of NO (MacMicking)

Synthesis of NO endows macrophages with cytostatic or cytotoxic activity against viruses, bacteria, fungi, and tumor cells (Nathan, Hibbs) thus decreasing inflammation.

During the inflammatory process a chemical is released known as myeloperoxidase (MPE).
This is the most powerful oxidant produced by the human neutrophil during acute inflammation, especially from infection or cancer. Betalains found in the Nopal cactus fruit extinguish the fire of inflammation caused by MPE and protect the healthy cells. Betalains rescue the cell by quenching the fire of free radicals.

There are times when the body cannot heal itself. If Inflammation overwhelms a cell it may be damaged beyond repair. Damaged, dead cells must be removed or they will become the focus of infection and illness. Betalains assist macrophage to engulf the dead cell and eliminate it from your body. Then, toxins are drained away from the cell and the protein matrix of Betalains permeates and reinforces the cell, returning it to health. In addition, Betalains drain toxic waste water surrounding the cells and create a cooling environment conducive to cell health.

It is estimated that 27 million Americans age 25 and older have inflammatory diseases like rheumatoid arthritis and osteoarthritis. Although osteoarthritis is more common in older people, younger people can develop it usually as the result of a joint injury, a joint malformation, or a genetic defect in joint cartilage. Both men and women have the disease. Before age 45, more men than women have osteoarthritis; after age 45, it is more common in women. It is also more likely to occur in people who are overweight and in those with jobs that stress particular joints. As the population ages, the number of people with osteoarthritis will increase and by 2030, about 20 percent of Americans – about 72 million people will have passed their 65th birthday and will be at high risk for the disease.

Osteoarthritis, sometimes called degenerative joint disease, is the most common form of arthritis. Osteoarthritis occurs when cartilage in your joints wears down over time. Osteoarthritis can affect any joint in the body, though it most commonly affects joints in the hands, hips, knees and spine. Osteoarthritis typically affects just one joint, though in some cases, such as with finger arthritis, several joints can be affected. Osteoarthritis gradually worsens with time, and no cure exists. But osteoarthritis treatments can relieve pain and help you remain active. Taking steps to actively manage your osteoarthritis may help the individual gain control over osteoarthritis pain. (American Cancer Society, 2008)

Rheumatoid arthritis (RA) is a chronic systemic disease of unknown origin that predominantly involves synovial tissue. RA affects 1.3 million Americans or 0.5%–1.0% of the global population, with females affected more frequently than males.

Rheumatoid arthritis is a serious disease and prevention and early diagnosis are the best treatment in order to prevent severe deformity and joint erosion. The etiology of RA is unknown but seems to be multifactorial. There is a certain genetic susceptibility, and studies in twins indicate a concordance of about 15%–20%. Environmental factors (smoking) or infectious agents are suggested to play a role in the etiology, but their contribution has yet to be defined (Oliver J. Sommer, 2003).

Literature Review:
Over many years we have found that preventing or reducing inflammation is all about the individual listening to his or her body as a warning signal that something is wrong and a rapid response is the solution to a more chronic disease. There are several markers in our blood, indicating inflammation, and one in particular the C-reactive protein (CRP), which can be easily measured to give us an indication of the level of inflammation present in our bodies. Many studies have examined the impact that vitamins such as folic acid and other B vitamins have on tissue function and inflammation.

These show a clear connection between adequate blood levels of certain nutrients, getting homocysteine and CRP- protein normalized, and lowering risk of health conditions caused by inflammation, in arthritis. Along with folic acid, other B vitamins and EFA’s, as described above, vitamin D too has a known anti-inflammatory effect, and vitamins C and E are widely celebrated as powerful antioxidants, countering the harmful effects of free radicals. Bioflavonoids are a class of over 5000 plant chemicals that our bodies metabolize in such a way that offers us strong anti-oxidant, anti-cancer, anti-allergenic and anti-inflammatory effects. Most antioxidant including betalins and bioflavonoids been used traditionally to promote vitality, reduce inflammation and protect against toxins and poisons. Recent research confirms that the Opuntia ficus indica or Nopal pear cactus juice contains the richest concentration of betalains of any plant in the world.

Betalains create health by balancing the environment inside the cell with the environment outside the cell and can be taken in supplemental juice form as part of a natural anti-inflammation regimen. Their study is helping to bring about a whole new range of anti-inflammatory agents that more safely and effectively target the inflammatory cascade well upstream of where conventional NSAID’s and COX-2 inhibitors cause their damaging and unwanted side effects.

Significant amounts of ascorbic acid may be also present in the Nopal cactus juice, ranging from 180 to 300 mg.kg (Cantwell, 1995; Piga et al., 1996; Sáenz, 1995). Cactus pear is higher in vitamin C than other common fruits, such as apple, pear, grape, and banana (Cheftel and Cheftel, 1983), while other vitamins, such as carotenoids, thiamin, riboflavin, and niacin are in trace amounts (Sawaya et al., 1983; Sepúlveda and Sáenz, 1990).

Vitamin C, also known as ascorbic acid, is essential for humans and is required for several essential metabolic reactions. Humans, however, unlike most other organisms, cannot synthesis vitamin C internally, requiring to obtain vitamin C from an outside source such as supplements or diet. Most commonly known, a deficiency of vitamin C in humans can cause scurvy. Vitamin C has several main functions in a healthy body; antioxidant activity, collagen synthesis, the essential part of connective tissue in the body, and support of the immune system, primarily with white blood cells. In some instances of microbial infection, the host fights the infection by producing enzymes that are regulated by inflammatory pathways that result in the creation of free radicals, including reactive oxygen intermediates.

It is a well-known fact that certain types of dietary fat, such as trans fats , and essential fatty acid they play a role in numerous health problems. An essential fatty acid must be obtained from the diet, as they cannot be synthesized in humans.

Polyunsaturated fatty acids, mainly linoleic acid, also was the predominant polyunsaturated acid found in the pulp and seed oil of the Cactus pear. The pulp predominates in linolenic acids, vitamin E and carotene with respect to seed oil (Ramadan and Mörsel, 2003b; Ramadan and Mörsel, 2003). The fruit has a high content of free amino acids, particularly proline and glutamine, the highest level being that of nutraceutical taurine, up to 572.1 mg/L (Stintzing et al., 2001). The mineral pattern is characterized by high amounts of calcium (up to 59 mg.100 g-1) and magnesium. Betalains from Nopal cactus juice reduce inflammation through antioxidant protection of the blood vessel lining and by reducing inflammation in the “bad” LDL cholesterol.4 What is more, Betalains prevent ICAM-1 from hardening the cholesterol compound.5 By doing this, Betalains from Nopal cactus juice provide protection for the delicate lining of the arteries and reduce the risk for heart attacks, stroke and other vascular diseases.

These fatty acids are thought to play a role in biological processes, and unlike other fats, do not play a role in energy production. Then-3 and n-6 fatty acids play a critical role in cell membrane phospholipids and enzyme substrates. These fatty acids are important because they play a vital role in numerous metabolic processes. Alpha linolenic acid (ALA) biosynthesizes EPA and DHA in humans (Terry, Terry, & Rohan, 2004), thus presenting an important and pertinent role of ALA.( Burdge, 2005).

Figure 1: This multi-step sequence of the metabolic pathway by which dietary ALA can be converted by a series of sequential desaturation (D) and elongation (E) reactions into EPA and then DHA in the mammalian liver

There have been many mechanisms proposed as to why n-3 fatty acids would assist in inflammation and cancer prevention and treatment. These mechanisms include, 1) suppression of arachidonic acid (AA), 2) influences on transcription factor activity, gene expression, and signal transduction, 3) alteration of estrogen metabolism, 4) increased or decreased production of free radicals, and 5) mechanisms involving membrane fluidity and insulin sensitivity (Larsson et al., 2004). .
Increased n-3 levels suppress the production of arachidonic acid , AA, which in turn suppresses the production of eicosanoids derived from AA. One of the most important functions of n-3 and n-6 is the enzymatic conversion into eicosanoids, a 20-carbon chain (Larsson et al., 2004).

“Cyclooxygenase (COX) and lipoxygenase (LOX) act on 20 carbon fatty acids to produce cell signaling molecules” (Hardman, 2004, p. 3428S). These fatty acids would be considered n-6 fatty acids. When COX is activated it produces prostaglandins or thromboxanes from AA or EPA (eicosapentaenoic acid). Leukotrienes are produced from LOX activity on AA and EPA.
The prostaglandins produced from EPA are not favorable to the growth and development of cancer cells, where as the prostaglandins produced from AA tend to be proinflamatory and pro-proliferative. When n-3 fatty acids are available, they are used by cyclooxygenase 2 (COX 2) as a substrate. COX 2 is one of two isozymes of cyclooxygenase. COX 2 is produced along with the inflammatory process and catalyzes the formation of prostaglandins and other eicosanoids (Llor et al., 2003; Larsson et al., 2004). N-3 is vital in this because it suppresses COX-2 activity, and competes with n-6 for COX to form eicosanoids (Larsson et al., 2004), that reduce the inflammatory response. This occurs by changing the type of eicosanoids that are produced. The more n-3 present, the more competition for enzymes and COX activity, thus down regulating the production of AA-derived eicosanoids. Therefore, if more n-3 is supplemented into the diet and cell membranes, there will be less productions of PGE2 in normal and tumor tissues (Hardman, 2004; Oomah, 2001). This is important since the inflammation process has been associated with cancer promotion (Hardman, 2004; Dietary Fat and Cancer, 1997; Diet and Breast Cancer, 1994).

Figure 1: Shows the n-3 and n-6 synthesis chains, along with the major eicosanoids from AA, EPA and DGLA also demonstrating how each fatty acid competes for the same enzymes throughout the cascade.

Importantly, in relation to the RA and OA, is because of the lowering of arachidonic-derived eicosanoids, CLA reduces tumorgenesis (Kavanaugh, Lui, & Belury, 2001; Park, Ryu, Ha, & Park, 2001). The reduction of arachidonic-derived eicosanoids can also be contributed to the inhibition of COX-2. CLA may be an antagonist for COX, which reduces the enzyme that is available for arachidonate.

The suggested mechanism for the ameliorating effects of omega-3 fatty acids (DHA plus EPA) on RA is a decrease in inflammation due to EPA’s ability to competitively inhibit omega-6 prostaglandins and thus increasing the production of LTB5, a non- inflammatory eicosanoid and decreasing the production of pro-inflammatory eicosanoids (eg. PGE2, thromboxane and LTB4). The result is decreased vasodilation, neutrophil degranulation, vascular permeability and hyperalgesia. This combination effectively decreases swelling, redness and loss of function which are the hallmark signs and symptoms of RA (Stamp et al ., 2005)..

Conclusion:
Natural nutritional supplements can be an effective part to be added on a classic arthritis treatment plan. Dietary supplements are not classified as drugs, but that doesn’t mean they can’t act like them in helping reduce inflammation. The increasing interest in cactus-pear and the multiple-ingredient should encourage research on health-promoting capacity of cactus pear. Although it is not yet confirmed clinically, the anti-inflammatory propriety of the Nopol cactus juice is definably linked to the variety of components and in particular on the presence of Betalain, vitamin C and fatty acids in the pulp and seeds of this fruit.

Betalains create health by balancing the environment inside the cell with the environment outside the cell. Betalains extinguish runaway inflammation by turning off enzymes that may be turned on by trauma, toxins, deficiency or stress. Betalains protect against toxins and poisons by building an impenetrable bulwark in the wall of blood cells, brain cells and all other cells in your body against the oxidation of premature aging. . Most of the mechanisms identified are associated with common functions of the cells and the avoidance of certain harmful processes, such as the reduction of oxidative damage when using the Nopal cactus juice.

Furthermore, the processes identified that both vitamin C and fatty acid supplementation deal with the natural processes, which are interrupted or increased when an inflammatory process forms. All of the published randomized controlled trials involving omega-3 supplementation with DHA/EPA from fish oil have shown a moderate benefit when combined with standard RA pharmacotherapy (Stamp et al.,2005). Furthermore, there have been reports that symptoms worsened after fish oil supplementation was ceased. Overall, these studies have established that a dose of 2.6 g/day or more of n-3 fatty acid supplementation (DHA+EPA) generally will reduce the symptoms of RA after about 12 weeks; consuming a larger dose will reduce this latency period (Stamp, LK., et al. 2005).

This article shows strong and consistent scientific evidence that Betalins, vitamin C and omega-3 fatty acid and other component present on the Nopal Cactus pear juice supplementation are effective at reducing inflammation and improving symptoms of RA and osteoarthritis. Dietary alteration when combined with standard RA pharmacotherapy provides an added opportunity to give patients some control over their health and management of their disease with out side effect typical of classic treatments.

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