auto-immune and stress study

Rheumatoid Arthritis

 by Hugo Allen-Stevens

Abstract

Rheumatoid Arthritis (RA) is an auto-immune condition characterised by a cascade. Triggers in the cascade include DNA and genetic expression, Gastrointestinal Integrity and Immune homeostatis. Mediatory factors include stress response, liver detoxification and the inflammatory pathways. Intervention and treatment at any point in the cascade (including prevention) may successfully reduce symptoms and inhibit or resolve expression at any point along the RA cascade. This paper will focus on the use of Dietary and Lifestyle factors as key tools in that intervention.

This paper will also bear reference to the case of a 73 year old female with RA who has in the last year undergone operations to replace her knees which were crippled by RA. This lady has in the last 10 years undergone increased physiological stress whilst acting as carer for her husband. This paper will address how long term stress impacted this lady’s RA cascade. It will also address how the death of this lady’s husband this year and the resultant reduction in stress may be factors that can be combined with nutritional and lifestyle support to address her RA cascade and ease her symptoms. This lady is the mother of the author of this paper.

Description of condition

The RA cascade involves anti-bodies that attack the synovial membrane between bones resulting in damage and degeneration of surrounding cartilage and bone tissue. Marieb notes that RA “begins with inflammation of the synovial membranes […] Inflammatory cells […] enter the joint […] and release a deluge of inflammatory chemicals that destroy body tissue […] In time […] cartilage is destroyed, scar tissue forms and connects bone ends” (2009, p. 173). Marieb further notes that “the course of RA varies as is marked by remissions and flare-ups (rheumat = susceptible to change or flux)” (2009, p. 173). Holford notes that during a remission, joints become “inflamed and enlarged, causing pain, swelling, stiffness and loss of function in the joints and possibly other parts of the body” (2009, p. 4). Holford adds that “sufferers may have a slight fever, they are likely to feel tired and generally run down” (2009, p. 5).

During RA remissions, “involved joints are characteristically quite warm, tender and swollen. The skin over the joint takes on a ruddy purplish hue. X-ay findings usually show soft-tissue swelling, erosion of cartilage, and joint space narrowing. As the disease progresses, deformities develop in the joints of the hands and feet, although deformities can [also] occur in the neck and shoulders” (Murray, 2005, p. 761). Most intriguing, however, is Holford’s assertion that RA “affects the whole body, and usually on both sides of the body (for example, both wrists, rather than simply a weight bearing joint). It often affects fingers, wrists, knees and ankles but can also affect other parts of the body such as heart tissue and muscle” (2009, p. 4). Holford provides a possible explanation for this stating that “some viruses and bacteria particularly affect joints by lodging in them and recurring when […] immune defences are low” (2009, p.13).

As such, a weakened immune system can place any part of the body at risk of RA symptoms. However the cascade that leads to that begins with antigen presentation, identification and immune response.

Cell related immune function

Choy and Panayi (2001) note that RA begins with the presentation of an antigenic protein that could be viral or endogenous. The end result of this presentation is the production of key cytokines that the authors note as being instrumental to the inflammatory process in RA. Those cytokines are: Interleukin-1 (IL-1), interleukin-6 (IL-6), and TNF-alpha (TNFa). IL-1 and TNFa are noted for stimulating neutrophil activity, and neutrophils are noted by the author for releasing enzymes that damage and degrade the proteoglycans in cartilage tissue. Furthermore, CD4 and T-Cell intermediaries, upon being stimulated by the antigen presentation, release chemical compounds that further degrade joint tissue (osteoclastogenesis). This results in the key characteristics of RA – the swelling and degradation of joints and cartilage due to the inflammatory immune response.

RA itself is characterised by periods of remission and “flare-ups” where the swelling of joints (and pain) returns. If this remission becomes prolonged, leading to chronic localised inflammation, degradation of both joint tissue and cartilage may be irreversible. Thus there is a key need to intervene before inflammation becomes chronic.

Simopoulos (2002) notes that dietary intake of fatty acids EPA and DHA from fish oil have been shown to modulate IL-1 as well as TNF production. The studies note prolonged down-regulation of IL-1 and TNF with supplementation. They also noted prolonged down-regulation of these cytokines after supplementation was stopped – indicating how fish oil supplementation can have a regulatory effect on excessive immune activity, returning activity to homeostasis. Also noted is the down-regulation in the production of Leukotriene B4 (LTB4). LTB4 is closely associated with neutrophil activity and down-regulation of LTB4 was shown to lead to down-regulation of neutrophils (neutrophils, as noted above, can damage cartilage tissue). Furthermore, down-regulation of LTB4 was prolonged after supplementation with DHA and EPA was stopped, again illustrating the possible immune regulatory effects of fish oil supplementation. Fish oil, as such, could have a function in reprogramming the immune system.

Simopoulos points out that incorporation of fish oil into the cell membrane of cells throughout the body is closely associated with the function of fish oil in regulating the immune system. Studies evidenced IL-1 and TNF numbers directly relating to the amount of EPA in cell membranes. Correspondingly, increased EPA in cell membranes necessitated less anti-inflammatory medication in RA suffers. So could fish oil function in reprogramming the immune system? Evidence presented by Simopoulos suggests it can. He points out that both fish oil and other Omega 3 sources (such as flax seed) are shown to be rapidly incorporated into cell membranes, particularly the membranes of monocytes. Furthermore, these oils competing with and displace other fatty acids, namely Arachidonic Acid (AA), for incorporation into cell membranes. When they do, they alter cell function by displacing proteins on cell membranes. This is turn results in altered expression by the cell as well as altered interaction with other cells. Furthermore, Omega 3 acids, as composites of cell membranes, suppress RNA genetic expression by monocytes and down-regulation of IL-1 and TNF production is a result of this. The net effect is that Omega 3 oils both down-regulate antigen presentation and the resulting immune cascade.

Simopoulous adds that the incorporation of Omega 3 oils into cell membranes is, itself, down-regulated over time. This suggests that Omega 3 oils reprogram the immune system and down regulate inflammatory responses, after which the body returns to homeostasis and recovers the ability to self-regulate the incorporation of other oils into cell membranes (needed, for example, for possible up-regulation of immune and inflammatory responses.) Over all, there is a clear function for Omega 3 in regulating inflammatory conditions where they are chronic.

Meanwhile other factors triggering a chronic inflammatory state will need to be monitored – especially in RA. These factors include the influence of stress and the adrenal hormones.

Adrenal Hormones

Kiecolt-Glaser (2003) points out over-production of pro-inflammatory cytokine IL-6 is associated with arthritis (as well as osteoporosis, type 2 diabetes, cancer and heart disease). In her study of long term caregivers looking after their spouses, she concluded that IL-6 levels rose in response to stress and remained high in many cases for years after the death of the spouse. She also notes how psychological and emotional factors can trigger the release of IL-6 leading to increased inflammatory damage from this cytokine when release is sustained over long periods of time – such as with caregivers. What is interesting to note is how psychological and emotional behavioural patterns can set up conditions by which pro-inflammatory  cytokines such as IL-6 will be automatically released and levels sustained. This leads to the possibility that the opposite is true – that the adoption of new emotional patterns of behaviour can break the same inflammatory cycle.

Straub and Cutolo (2001) note that long term release of IL-6 disrupts the function of the Hypothalamus and Pituitary glands and their release of both ACTH (AdrenoCorticotropic Hormone ) and CRH (Corticotropin-Releasing Hormone) – effectively leading to disrupted adrenal hormone response. Such a factor could lead to disrupted energy patterns leading to blood glucose imbalances. More important is the disruption to the anti-inflammatory effects of adrenal and gonadal hormones. Straub and Cutolo note that Cortisol, DeHydroEpiAndrosterone (DHEA), Adrenaline, Testosterone (as well as CNS neurotransmitters adenosine and norepinephrine) all have a regulatory effect on key inflammatory cytokines (IL-1, IL-6 and TNF) involved in RA. However they note that sustained cytokine release inhibits sex hormone production. Furthermore, IL-6 converts Estrogen to proinflammatory estradiol. In effect, a chronic inflammatory condition such as RA can be self-sustaining and lack regulatory control, especially when stress is chronic. This lack of regulatory control can lead to RA (or stress) spinning out of control affecting other organ systems, such as the endocrine system.

Straub and Cutolo (2001) also note that inflammatory cytokines not only down-regulate sex hormone production (via the Hypothalmic-Pituitary-Gonadal Axis) but also up-regulate ACTH release via CNS activation. This is echoed by Kharrazian (2009), who points out how Cortisol release is stimulated by inflammatory conditions. As mentioned above, sustained IL-6 circulation eventually leads to down-regulation of Cortisol (via disruption to the Hypothalmic Pituitary axis). However this delicate balance of regulation (presumably functioning to force the body to withdraw from stressful encounters in order to recuperate fully) could presumably be ignored – and stress response  stimulus of Cortisol could be chronic in itself. The danger here is not just increased risk of inflammation (pointed out by Kiecolt-Glaser) but also thyroid hormone problems and adrenal, as well as sexual hormone disruption. Kharrazian (2009) notes that either prolonged stress or chronic inflammation can lead not only to disrupted T4 function and T3 synthesis, it also leads to neurotransmitter problems. And in a sustained spiral of increasing organ system disruption, Straub and Cutolo point out how inflammatory cytokines stimulate the aromatase enzymes and disrupt steroid hormone production – in this case producing estrogen which can then be converted into the pro-inflammatory estradiol. There thus is a clear need for intervention at any point in this cascade, and especially before stress or inflammation in the RA cascade becomes self-sustaining and lacking regulation.

In the case of the mother of the author of this paper, the net effect of this stress response can be seen in the worsening of this lady’s RA condition in the last ten years whilst acting as caregiver – whereby inflammation became chronic as a result, and degradation of synovial membranes in both knees became irreversible. This resulted in the necessitation of surgery to replace those knees. Whilst the stress of acting as caregiver no doubt increased her RA inflammation and led to that joint degradation, this could continue even when that stress apparently disappears. And Kiecolt-Glaser (2003) point out the possibility of stress response being prolonged even after the death of a husband when the wife is the caregiver. They furthermore point out a worsening of the symptoms of RA and also the increased risk of diabetes and heart problems.

If sum, prolonged stress can bring the body to a unregulated pro-inflammatory state, and also disrupt and pose a danger to the endocrine system homeostasis.  There is a thus a clear need for intervention to disrupt stress, the stress response and the dangers they pose. As pointed out above, intervention in the psychological and emotional programming that occurs during chronic stress can disrupt stress response and its influence in inflammatory conditions such as RA. And this could be effected using mind body techniques and lifestyle adjustments (which are detailed later in this paper).

Intimately related to an unregulated adrenal or inflammatory process is the risk of intestinal inflammation being triggered. In fact, intestinal health and inflammation in the Gastro Intestinal (GI) tract can itself be a trigger for the RA cascade.

GI Integrity

Nuclear Factor-κB (NF-κB) is another key cytokine and intermediary in the inflammation pathway. Vojdani and Lambert (2011) point out how factors such as stress and the use of pharmaceuticals can cause bacterial imbalance as well as bacterial crossing of the mucosal lining. They also point out how antigens (such as food allergens) can increase intestinal Tight Junction (TJ) permeability. These factors, amongst many others, trigger immune responses.

Vojdani and Lambert (2011) also point out the key roles of IL-1, IL-6, and TNF in the consequential inflammatory process. They implicate IL-1 as playing a key role in increasing TJ permeability and NFkB as playing a key pivotal role in the resultant enhancement of the inflammatory process. And this process they point out can lead to increasing gut permeability, up-regulated immune stimulation, and an inflammatory cascade that involves permeability of the Blood Brain Barrier and Gastrointestinal Dysfunction.

Due to either RA or the inflammatory response to GI aggravation, the resulting increased circulation of IL-1, IL-6 and TNF may lead to an enhanced sensitivity and triggering of the immune processes involved in either inflammatory pathway (RA or GI permeation). Effectively, one can affect the other, causing an increasing up-regulation of inflammatory processes – both working synergistically to increase each other’s inflammatory cascade. An important factor to note is that GI permeation and inflammation will cause nutritional deficiency (due to decreased absorption) which will detrimentally starve all organs and body functions of key nutrients for homeostasis. Of those functions, immune system homeostasis, if detrimentally affected, could lead to down-regulation and bacterial invasion of body tissues. This in itself is a key factor in the RA cascade – whereby bacteria enters joint synovial fluid activating the inflammatory process.

Another key potential cause of auto-immune disorders such as RA and GI permeability could be immature lymphocyte T and B cells being released before they are sufficiently programmed and thus are “self reactive” to body tissues (Marieb, 2009, p. 429). In a weakened, nutrient deprived state caused by a chronic inflammatory condition, the potential for release of these “self reactive” immune cells could be enhanced and in itself become a trigger for either disorder through immune memory cell programming.

Unwinding these inflammatory processes could be effected using dietary measures. Ichikawa et al. (2006) report that Withanolides in Aswagandha root inhibit NFkB. They also identify suppression by these Withanolides of osteoglastogenesis by NFkB – thus a lowering of the joint damage in the RA cascade. Mulabagal et al. (2009) built on the work of Ichikawa et al. in proving the effective use of Aswagandha Withanolides in suppressing COX-2 enzymes in the Arachidonic Acid inflammatorial cascade. In addition, Chattopadhyay et al. (2004) point out that COX-2 enzymes may be down-regulated due to the broad anti-inflammatorial profile of Curcumin in Turmeric root: they point out that Curcumin has been proved to reduce both TNF and NFkB genetic expression, reduce COX-2 activation, and also have powerful anti-oxidant effects. In addition, Altman et al. (2001) report that Ginger root down-regulates inflammatory compounds such as TNF through inhibition of COX and LipoOxygenase enzymes in the Arachdionic Acid pathway. Meanwhile, Linos et al. (1999) point out the inhibitorial effect of Oleic Acid in Olive Oil on key inflammatorial compounds such as LTB4; their work further illustrates the beneficial effects of dietary fatty acids in flax seed and fish oil and thus adds to the beneficial effects of Omega 3 oils reported by Simopoulos (2002). Garlic, meanwhile, has well noted anti-biotic effects that may be of use in regulating or assisting the immune system involved in inflammatory responses.

Pharmacological intervention

The beneficial use of natural nutrients in treating both GI and RA cascades is well noted in the above studies – especially with regard to their avoidance of problems caused by pharmacological drug treatments of such conditions. Rakel (2007) details these treatments as including Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), Corticosteroids, DMARDs (Disease Modifying Anti-Rheumatic Drugs), as well as other immune-suppressive drugs (such as anti-TNF agents) and also Anti-biotics.

Both Rakel (2007) and Holford (2009) point out the increased risk resultant from the use of these drugs in terms of heart disease, osteoporosis and diabetes, as well as intestinal problems. Holford (2009) notes that NSAIDs decrease immune prostacyclins that act in the GI tract to both protect and repair gut mucosal lining. It should be noted that damage to this lining will increase GI permeability and the cascade that could contribute to the RA cascade. Also, Vojdani and Lambert (2011) point out that medical drugs can upset the balance of gut intestinal bacteria that leads to GI permeability. Additionally, upset caused to this bacteria will lead to and contribute to the formation of food intolerances and allergies, as well as dysbiosis of the colon. And it is these GI problems that should be avoided in treatment of RA and intervention in the RA cascade.

Dietary intervention

“Virtually any food can aggravate RA, but most common offenders are wheat, corn, milk, dairy products, beef, nightshade-family foods (tomatoes, potatoes, eggplants, peppers)”

(Murray, 2005, p. 762)

Due to the inter-relationship between auto-immune conditions like RA and food intolerance and allergenic response factors, Murray (2001, 2005), Rakel (2007) and Holford (2009) advocate identifying and removing possible food allergens. This principle cannot be emphasised enough, for health in the GI tract is needed to supply the body with the nutrients it needs to achieve homeostasis. Rakel and Murray both advocate fasting as a first step in mediating RA symptoms and possible dietary triggers of its onset. And both emphasise fasting followed by the reintroduction of foods avoiding common allergenic aggravators (such as those listed by Murray above). Murray further emphasises a vegetarian diet both as a method to avoid availability of saturated fats for use in the Arachidonic Acid pathway and to provide anti-oxidant support for immune function. It could also be noted that plant based foods down-regulate blood acidity: high blood acidity is associated both with a meat based diet and is further implicated in increasing pain and inflammation.

Kjeldsen-Kragh (1999) further notes the beneficial effects of dietary intervention. He studied the use of dietary fasting as well as the use of vegan and vegetarian diets in controlling pain and swelling in RA patients. He attributed improvements in patients’ conditions from these dietary approaches as stemming largely from beneficial effects of fiber:

“The diet changes the fecal flora and thereby alters the amount and type of bacterial substances absorbed by the intestinal mucosa. The absorbed bacterial substances in turn influence the inflammatory process in the joints.

“The cause-effect relation may be the opposite. Rheumatoid arthritis is a systemic disease that can affect almost all tissues, and a reduction in disease activity may also involve the intestine. Changed conditions in the bowel can in this way influence the growth conditions of the intestinal bacteria and thereby alter the balance between the different species of the microflora.”

(Kjeldsen-Kragh, 1999)

Kjeldsen-Kragh’s study could also have highlighted the possible beneficial effects of nutrient deprivation in a vegan or vegetarian diet, namely reduced protein intake for forming immune compounds. Kjeldsen-Kragh did not specify this, but nutrient deprivation through fasting or a restrictive diet (such as a vegan or vegetarian diet) could be used as a method for immune-suppression and down-regulating excessive immune and inflammatory activity. However it is in the opinion of the author of this paper that ensuring full support for immune function using key nutrients along with lifestyle modifications would provide better tools for addressing the RA cascade. Furthermore, fasting and nutrient deprivation should only be used under expert supervision to interrupt and reset an unregulated (ie chronic) inflammatory condition such as RA.

Other uses of fasting are to provide the GI tract a chance to heal. This is especially necessary when dietary inflammatory aggravators are being ingested. Vojdani (2011) notes the effect of dietary antigens in increasing TJ permeability. Cordain et al. (2000) further expands upon this noting the effects of dietary lectins in both increasing TJ permeability as well as aggravating enterocyte function in the intestinal tract, leading to dysbiosis as well as degradation of the intestinal villi. Furthermore, with the ability to cross the intestinal tract, Cordain et al. then showed that lectins altered lymphocyte function prompting auto-immune triggering of both the RA cascade and other auto-immune disorders. Furthermore they pointed out that lectins could trans-locate after entering to the synovial membranes (of joints), again triggering the RA cascade. Cordain et al. do point out however that lectin activation of both RA and GI disease pathways is possible is some but not all cases of these disorders.

Cordain et el. (2000) back-up Murray (2005) in asserting that wheat is an aggravator of RA (albeit in some but not all cases). Cordain also point out that other lectins, such as those from red beans and other pulses such as lentils, are again aggravators of RA. And nightshade family vegetables, such as potatoes and tomatoes, are again high in lectins and thus potential aggravators as well as initiators of the RA cascade (as well as potentiating GI inflammation and permeability). Cordain et al.’s study thus shows the intricate relationship between GI health and the RA cascade. They also point to the benefits of fasting in lowering both RA and GI inflammatory processes. This combined with Kjeldsen-Kragh’s study of fasting as well as the numerous studies of fasting cited by Murray (2001, 2005), Rakel (2007) and Holford (2009) point to a possible benefit of fasting in treating RA. These studies, however, are not conclusive in their evidence for the benefits of fasting – and many patients under study achieved no benefit.

The author of this paper thus once again concludes that fasting has a potential use in treating RA patients, but under expert supervision. With that supervision, and the re-introduction of foods under supervision and testing, food allergens and aggravators may be identified and eliminated. What may be concluded with that supervision is that food poses no role in aggravating or initiating the RA cascade. However the potential for lectins as well as other potential dietary allergens such as gluten and lactose to be aggravators must be tested – under expert supervision.

Immune support and a 7 or 14 day nutritional program

The role of food nutrients in supporting immune health is the reason the author advises fasting only under supervision. Following that fast, identification and elimination of food allergens is best done with an expert – which potentially could be a 7 or 14 day dietary treatment. Another form of treatment during a 7 to 14 day treatment period could be to providing nutritional immune support. Again, the author advises this be done under expert supervision with immune marker testing. This is due to the potential to use nutrition for down-regulation as well as up-regulation of immune or inflammatory systems. For example Murray (2001) illustrates the potential use of food in up-regulating T-suppressor to T-helper ratios in auto-immune conditions such as RA, as does Haas (2006). This again points to a role of reducing nutrient intake of key foods (such as protein) in order to suppress the immune system. Again however, the author stresses that expert supervision is needed. Otherwise, and assuming GI health is intact, the author advocates immune support through adequate nutrient support.

The possible nutrients that will support immune function are outlined by both Murray (2001) and Haas (2006). Haas advises sufficient protein intake, as well as sufficient intake of Vitamins A, C, E, B1, B2, B3, B5, B6, B12 and Folic acid, the minerals Selenium, Magnesium, Zinc. Haas also advocates intake of Bioflavonoids, Carotenes, Essential Fatty Acids and judicious intake of Iodene, Copper, Iron and Zinc (considering the possibilities of them off-setting each other in absorption or having detrimental effects if taken in excess). Haas also advises intake of Garlic and the use of Goldenseal and Licorice Root as immune supporting herbs. Murray (2001) adds to this list of medicinal herbs stating Echinacea and Astralagus may be taken for short periods with beneficial effects. Meanwhile he advocates a whole food diet with reduced sugar and decrease saturated fat, all to support immune function. As noted above, in Murray (2005) he advocates reduction of meats with saturated fats in order to suppress the Arachdionic Acid pathway. In the same book, Murray advocates the use of dietary enzymes such as Papain and Bromelain in helping with the RA cascade. Holford (2009) advocates the use of Bromelain for its anti-inflammatory effects. Other anti-inflammatory foods Holford recommends are Bioflavonoids (such as Quercetin), Ginger, and the herb Boswellia, as well as Hops extract and Olive extract.

The potential therefore is for a 7 or 14 day dietary program to include a fast, followed by a food elimination program. In doing so, it could follow the “4 R” principal advocated by Bland et al. (2004). In doing so it would include a GI healing program (to “replace” dietary enzymes and stomach acid, as well as “reinoculate” the GI tract with healthy bacteria using probiotics and prebiotics). Finally it would include a “repair” process, involving the introduction of a low irritant diet and GI dietary support that includes anti-oxidants and L-glutamine.

Bland et al. (2004) also point out the use of Omega 3 oils in the Arachidonic (AA) cascade, pointing out how they may be used to attract desaturase enzyme activity  away from desaturating Omega 6 fatty acids into AA cascade. Bland et al. also point out how fish oil, flaxseed oil and primrose oil may all provide fatty acids that may be used for production of anti-inflammatory prostaglandins. Holford (2009) notes that the enzymes needed to desaturate these oils for prostaglandin production need support from Vitamins C, B3 (Niacin) and B6, as well as Biotin and the minerals Zinc and Magnesium.

The above advice echoes and adds to the findings of Simopolous (2002) regarding the use of Omega 3 in re-regulating the immune system, namely Omega 4 oils being incorporated into cell membranes. Bland et al. (2004) illustrate that the beneficial effects of Omega 3 oils being taken into cell membranes (and altering their function) depends on thyroid hormone homeostasis. However Kharrazian (2009) points outs out that thyroid hormone homeostasis may become unstable as a result of both chronic stress and chronic inflammation. In effect, the need to modulate stress once again should be a central feature of any dietary treatment.

Bland et al. (2004) also point out the use of nutritional inhibitors of enzymes in the AA cascade, namely Quercetin, Vitamin E, Turmeric, Ginger, Garlic and Onion, as well as herbal inhibitors such as Licorice, Turmeric, Boswellia, Black willow and Wintergreen. This echoes key findings from studies cited above and underscores the use of nutritional aids as substitutes for pharmacological medicines in treating patients with RA. However, full function of these nutrients requires not only additional nutritional support (to aid the desaturase enzymes for example), they also require support from hormone glands (such as the thyroid) as well as GI integrity. This should be taken into account when selecting a 7 to 14 day program for a patient with RA.

Holford (2009) points out that RA sufferers may need nutritional support for their joints, and to provide the body with the materials to form and prevent the breakdown of proteoglycans, the structural components of joints, synovial fluid and cartilage that are all damaged in the RA inflammatory cascade. In particular he points out the use of Glucosamine, pointing out how it is not only an essential component in making cartilage and produced in body, but that a Chinese study shows it has similar anti-inflammatory and pain reduction properties to ibuprofen [1] (Holford, 2009, p. 184). He also advises adequate intake of Vitamin C, D, the minerals Calcium, Magnesium, and Sulpur containing foods (such as eggs, onion and garlic) as well as supplementation with Chondriotin, all for joint health, as well as bone health. Bone health should be addressed in a dietary program as Holford notes the probability of bone damage both from RA induced inflammation and also hormone disruption (namely progesterone and estrogen).

Under supervision of a dietary expert, the correct 7 to 14 day treatment plan may be carefully chosen from any of the above ideas. Care should be taken with the allergenic foods and RA aggravators at all times. Meanwhile, care should be taken with aggressive treatment plans involving fasting, nutrient deprivation or supplementation. For example, altering the T helper to T regulatory ratio with the use Vitamin D, Fatty acids EPA and DHA, Glutathione, and SuperOxideDismutase may be useful in treating auto-immune cases, it may not be useful for all cases. For this, as with any other specific dietary advice for a 7 to 14 day period, the specifics of the diet relate to the specific situation of the patient (such as age, lifestage, stage in the RA cascade, amongst other considerations). The author of this paper cannot stress enough the need to tailor any 7 to 14 day dietary program to the specific needs of the patient.

Additional nutritional support for key body functions include liver support, anti-oxidant support and blood sugar management. All these could be built into a 7 to 14 day nutritional program – though the author emphasizes that they should be used as part of a longer term lifestyle change for RA patients that also includes stress management.

Liver support

Whilst the health of the GI tract and that of the immune system are closely inter-related (especially with relation to the RA cascade), the RA cascade, as noted above is closely related to the endocrine glands and stress response. Stress, it itself, is closely related to liver function due to the liver’s role in breaking down and eliminating stress hormones. Added, the liver plays a key role in eliminating environmental toxins such as chemical pollutants and medications, toxins that can lead to and trigger the GI permeability cascade.

What is important to note is that many of the key nutrients required for successful liver function and detoxification are exactly the same as those required by the immune system – thus enhanced immune activity, such as in the potentially chronic inflammation in the RA cascade, could lead to nutrients being deprived for use in liver detoxification and function. Conversely (and more likely given the liver’s receipt of blood and nutrients prior to the immune system) extra nutrient use in liver function in breaking down stress hormones or environmental toxins could lead to key nutrients being deprived for use in the immune system. Meanwhile, GI health again is paramount in determining the supply of the key nutrients needed by both the liver and the immune system.

Dietary fiber, as noted above, is needed for GI bacterial balance. It is also needed for assisting in bile secretions from the liver – bile being one of the most important mechanisms by which detoxification end products of the liver are taken from the liver. And fiber has a key role in assisting in preventing the reuptake of these end products in the GI tract (such as hormones that have been broken down) and ensuring their successful elimination from the body. Fiber also plays a key role in blood glucose management which plays a key role in adrenal hormone function and stress response.

Anti-oxidants, such as bioflavonoids, are required by both the liver and the immune system, and their use (and subsequent need for replacement) will be greater in the case of either liver or immune system activity. Bioflavonoids, meanwhile, are needed for collagen health which will be of paramount concern in the RA cascade. Another key nutrient used in both the immune and liver systems is Glutathione. Equally, nutrients required for methylation pathways are required for both liver detoxification and to ensuring homocysteine levels do not in themselves become inflammatory and a burden on immune system resources.

The key nutrients needed for optimal liver function include Betaine (from Beets and fish) used by the liver to process fat, prevent chemical damage ad assist in the metabolism of homocysteine. Choline from egg yolks, organ meats, orange and cauliflower) is another nutrient needed by the liver for exporting fat from the liver and preventing its build up there, as well as being used methylation reactions. Meanwhile, key liver detoxification pathways are

  • Glucuronidation (for breaking down many medical drugs, estrogen and other hormones) which requires nutritional support from sulphur containing foods (such as garlic) and limonene rich foods (such as citrus fruits, dill and caraway)
  • Glutathione conjugation and anti-oxidant activity: Glutathione is made from amino acids methionine and cysteine as well as other source nutrients (such as Selenium) that can be sourced from asparagus, avocados, walnuts, Brassica family plants, and fresh fruits, fish and meat
  • Methylation (for breaking down estrogen and other steroid hormones) which needs nutritional support from Choline, Vitamin B12, Folic acid (from green leafy vegetables); vitamin B6 (from whole grains and legumes); Vitamin B12 (from animal products and supplements)
  • Sulfation (is the main pathway for breaking down environmental toxins, microbial products, drugs and stress hormones) and which needs nutrient support from sulphur containing foods such as egg yolks, red peppers, garlic, onions, broccoli, brussel sprouts as well as amino acids methionine and cysteine

Anti-oxidant support

Both the liver and the immune system, especially during enhanced activity such as increased steroid hormone detoxification or inflammatory response, produce free-radicals. RA itself produces free radicals at sites of inflammation, free-radicals that can build up and cause collateral damage if they are not neutralised by anti-oxidants. Part of the damage done by free-radicals (or Reactive Oxygen Species: ROS) is damage to cell structure and function. ROS also damage DNA, cause the triggering of RNA, and lead to the expression of genetic predisposing factors to diseases such as RA. ROS damage thus may play a causal role in triggering the initial phase of the RA cascade.

However at any part in the RA cascade, Anti-oxidants will be needed to prevent ROS damage and build up during inflammatory immune response. They will all be needed to assist liver detoxification pathways and to support immune health. It is important to note that anti-oxidants have a synergistic effect – enhancing effects when working in combination with each other (eg Vitamin C being boosted by Carotenes). Key anti-oxidants are:

  • Carotenes found in fruits, especially darker fruits such as berries, cherries; and in vegetables: including broccoli, onions, greens, parsley; legumes; green tea and red wine; ginkgo bilboa. Carotenes also enhance immune functions, are anti-tumor, and work primarily to stimulate anti-oxidant mechanisms
  • Flavonoids found in dark-coloured vegtables such as: carrots, squash, spinach, kale, sweet potatoes; fruits such as cantaloupe, apricots. Flavonoids are also anti-inflammatory, anti-allergenic, anti-viral and anti-cancer properties, working primarily to protect cell integrity, function and response
  • Vitamins C and E, Zinc, Copper, Manganese: reduce superoxides through superoxide dismutase enzymes
  • Vitamin C – needed to enhance oxidative capacity and prevent ROS damage and acts as ROS scavenger
  • Vitamin E – very good for reducing exercise induced ROS; protects phospholipid bilayers of all cells; ROS scavenger and important for oxidative stress conditions
  • Coenzyme Q10 (CoQ10): has central role in aerobic metabolism and avoidance of ROS production through enhanced electron transfer capabilities in ATP reactions
  • Selenium: supports production glutathione peroxidase enzyme, which counteracts peroxides, stimulates immune response, and protects against toxins
  • Vitamin B2: assists in maintaining electron balance (and avoiding ROS formation)
  • Sulfur containing L-cysteine and methionine: ROS trappers
  • L-Carnithine: synthesized from lysine (needs Vitamin C) increases utilization of fats in ATP energy production, prevents oxidation and ROS formation

Stress, Pain and Blood Sugar Management:

As mentioned above, Cortisol, Adrenaline and Noradrenaline all have an immune-regulatory and anti-inflammatory effect which can be beneficial in the RA cascade. However, chronic stress leads to imbalances in other endocrine hormones (such as the thyroid and sex hormones). Long term stress  can also raise IL-6 levels that can itself trigger the RA cascade. Meanwhile triggering of the RA cascade can lead to raised levels of IL-6, THF and IL-6 that can disrupt DHEA and sex hormone production. Progesterone, needed to build bone tissue, may thus be down-regulated, with osteoporosis as well as other arthritic conditions being worsened. There is thus a clear need to manage stress during periods where the RA cascade is triggered. Key to this is ensuring liver breakdown of stress hormones through liver support. Added, stimulants such as nicoteen and caffeine not only increase the stress response, they also place an extra burden of toxic substances needed to be broken down by the liver. These stimulants also inhibit stress hormone breakdown (in the case of caffeine and its effect on adrenalin breakdown). And Heliovaara et al. (2000) further demonstrated a causal link between coffee consumption and the risk, and incidence, of RA. In effect, coffee, caffeine and smoking should be avoided and stress should be managed at any stage in the RA cascade.

Holford (2009) points out meanwhile that stress and stimulants (such as caffeine) increases blood  glucose levels that in turn increase inflammation – as such, excess blood glucose can make inflammation more chronic. Insulin, meanwhile, has an anti-inflammatory effect by reducing blood glucose. However, Holford notes that insulin has inflammatory effects in converting Gamma Linolenic Acid (GLA) for use in the Arachidonic Acid pathway. It therefore becomes key for a patient with RA to manage their blood sugar and curb excesses of either glucose or insulin in the blood. A key nutritional tool for this is fiber due its regulatory effect of glucose uptake to the blood in the GI tract. Holford meanwhile advises management of blood glucose via the Glycemic Index dietary principles. With relation to stress, particularly recovery from chronic stress, as well as replacing poor dietary habits (ie excessive sugar consumption) with healthier eating practices, the use of the Glycemic Index diet could be a nutritional aid to both lifestyle change and also stress management. The principle here would be to use a low stimulant, high fiber, managed Glycemic Index profile in order to effect a physiological change that could accompany and synergise with stress reducing techniques. And the author in this instance advocates using these dietary principles to effect lifestyle changes.

A key tool for managing stress, processing stress hormones, and benefiting the immune system is exercise. Kiecolt-Glaser et al. (2003) note how exercise down-regulates IL-6. Meanwhile, exercise can be used to strengthen joints, increase motility of lymph fluids and clearing of immune (and metabolic) wastes. Exercise also improves mood, increases metabolic rate and increases energy levels. Water exercises are most beneficial due to lack of joint stress – however weight bearing activity is needed to prevent bone damage and osteoporosis. Tai Chi and Yoga can be extremely beneficial for any stage of the RA cascade, as well as preventing it – especially with regards to calming the nervous system and down-regulating stress responses.

Rakel (2007) points out how mind body therapy can help with people is the RA cascade and in stress management. A key suggestion he makes is journal writing about stressful events in order to clear them. He also suggests journaling positive emotions (presumably to promote them and the sense of wellbeing). Holford (2009) echoes the value in this, pointing out the toxic side effects of repressing or holding in negative emotions (evidencing a study on the low incidence of RA in people who did not inhibit their impulses and ended up in prison [2]). Rakel also points out the value of meditation and mindfulness training, such as meditative walking, pointing out decreased pain and the possibility of recovery from a debilitating experience of RA inflammation. Murray (2001) expands upon this, indicating the value of meditative practices such as guided imagery, hypnosis, relaxation and positive mental attitude in promoting homeostasis. Murray and Rakel, meanwhile, both indicate the value of laughter, and Murray points out how positive emotions enhance homeostasis. Rakel also points out how being creative, finding meaning in life, trying new things, having positive relationships and the possible use of psychotherapy can all be useful in preventing and treating RA. What is important to note is that not only do all these therapies provide relief from the symptoms of RA, they also provide relief from stress. Meanwhile Rakel adds that Acupuncture and Laser Therapy both have low risks and high success rates in alleviating pain and swelling.

Summary

RA itself is a cascade and an individual may find themselves at any point in that cascade. Factors in that cascade include genetic predisposition, excess ROS damage triggering RNA expression, GI permeability leading to bacterial infection of joint tissue, and inflammation as well as stress responses becoming chronic and unregulated by the body. Added in that cascade are symptoms of pain, swelling and potential lack of joint mobility leading to the necessity for surgery. Intervention in that cascade and remedial treatment will depend on where the individual finds themselves. Broadly speaking, fasting, identifying and eliminating allergenic and RA aggravating foods, mind body therapy as well as stress management techniques all form part of an initial treatment of an RA flare up. And where stress has been chronic, mind body therapy becomes more important: in order to interrupt psychological and emotional patterns and engage individuals in more positive patterns, lifestyles and (supportive) relationships. With expert accompaniment, nutritional therapy can support this process.

Pharmacological drugs are noted for being useful in acute situations of inflammation and pain. However due to their damaging side effects, the use of Omega 3 oils, Turmeric, Ginger, Ashwagandha (as well as Olive Oil and Garlic) are noted for being more beneficial. These natural forms of medicine are also noted in studies for assisting RA patients to stop taking Pharmacological drugs as well as effectively treat less acute conditions.

Elimination and avoidance of toxins, as well as stimulants such as caffeine is recommended, as is key nutrient support of the liver. This support becomes more important during chronic inflammatory episodes due to the relationship between nutrient needs of both the liver and the immune system. And liver support is needed for recovery from an inflammatory flare up. Meanwhile, Anti-oxidants are needed – in prevention, treatment and recovery in all stages and phases of the RA cascade. Anti-oxidants are also needed for immune and liver support.

A plant based diet that avoids saturated fatty acids from animal products is recommended – not just to avoid the inflammatory effects of those fatty acids, but also to enhance intake of fiber. Plant fiber is needed for assisting liver functions as well as ensuring GI health – it also is needed to regulate blood glucose. Blood glucose will need to be monitored, especially with patients involved or recovering from chronic stress, and a low Glycemic Index Diet is recommended in such cases. It is further recommended by the author or this paper that these changes in diet become permanent in the lifestyle of people at any stage of the RA cascade – as is the increased regular intake of deep sea fish such as salmon due to their Omega 3 oils.

Exercise, meanwhile, should be a permanent feature of any person in the RA cascade, especially those involved in stressful lifestyles. Intense exercise training such as weight lifting, power yoga, aerobic exercises (such as running) as well as other sports involves a person in a lifestyle of exercise that may have positive and preventative effects of RA triggering. Regular surfing and contact with salt water can also be beneficial, especially in the leaching of inflammatory compounds (through osmosis) from sites of inflammation – this effect is noted by this paper’s author through his personal experience. Equally the author notes from personal experience that QiGong and advanced level training exercises, such as “Bone Marrow Washing”, are extremely beneficial in treating and preventing inflammatory disorders such as RA. Meanwhile, light exercises such as Tai Chi, Pilates, and light Yoga (as well as Yoga breathing exercises) are all beneficial for patients who are in an inflammatory RA episode, as is swimming. Above all, it is recommended that regular and ongoing exercise of any form, particularly lighter exercises, becomes part of the permanent lifestyle adopted by RA sufferers.

In addition to this, nutrient intake should be optimised – both by ensuring health of the GI tract (through avoiding allergenic foods for example) as well as taking key nutrients to support key body functions.

Conclusion

RA is a cascade triggered and mediated by a number of differing and inter-relating factors – stress and diet being key contributing factors to the onset or worsening of symptoms. Conversely, stress management and diet are the mediating factors where solutions, relief and preventive treatments may be found. Dietary and lifestyle change consisting of a permanent, sustainable set of practices to manage both RA symptoms, the RA cascade itself and stress effectively can be begun in a 7 to 14 day dietary therapy or treatment. However it is strongly recommended by the author of this paper that all people with RA consult a nutritional expert and begin dietary treatment under their supervision. This is due to the highly individual nature of both the testing and analysis that will need to be done, as well as the individually tailored course of treatment, therapy and lifestyle adjustments to each person’s individual requirements.

References:

[1] Jang B.C. et al. (2007). Glucosamine hydrochloride specifically inhibits COX-2 by preventing COX-2 N-glycosylation and by increasing COX-2 protein turnover in a proteasome-dependent manner. Journal of Biological Chemistry, 282 (38), 27622-27632

[2] Study conducted by Dr Ronald Lamont-Havers whilst he was national medical director of the Arthritis and Rheumatism Foundation. “Crime doesn’t pay but keeps arthritis away”, Los Angeles Times, 23 January 1963

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