Diet and arthritis
Studies have demonstrated a strong link between diet and arthritis. In particular people who eat foods rich in polyphenols (Fruit, vegetables, teas, herbs, spices, pulses), have a lower risk of osteoarthritis-related, musculoskeletal inflammation [Wang, McAlindon, Williams, Hanninen]. Clinically studies have confirmed a beneficial link between diet and arthritis in a trial were participants fasted, reduced salt intake and increased consumption of vegetables [Muller]. Another study confirmed a fasting followed by a diet of green vegetable and cruciferous-rich vegetables helped number of tender swollen joints, duration of morning stiffness, grip strength and markers of chronic inflammation – erythrocyte sedimentation rate and C-reactive protein [Kjeldsen-Kragh]. These and others from Mount Sinai School of Medicine as well numerous laboratory experiments have highlighted the benefits of adopting a lifestyle to reduce chronic inflammation. In addition to exercising regularly and stopping smoking dietary issues include:
Dietary issues which increase inflammation:
- Being over weight
- Processed sugar and refiled carbohydrates – tips to reduce sugar intake
- Excess alcohol – tips for sensible alcohol intake
- Identify any food allergies such as gluten and lactose which set up chronic gut inflammation.
- Fried and processed foods, such as fried meats and prepared frozen meals
- Advanced glycation end product (AGE), a toxin that appears when foods are grilled, fried, or pasteurised.
Dietary issues to reduce chronic inflammation:
- Eat more plant based proteins – Soy, lentils, quinoa, chickpeas, beans – buckwheat
- Eat more fruit and vegetables
- Eat more polyphenol rich foods – see below
Particular benefits of polyphenol rich foods.
Unlike conventional drugs which relive the symptoms , polyphenol rich foods potentially help prevent the onset of progression of the underlying joint damage via a number of biochemical pathways:
- Anti-inflammatory properties, which reduce the discomfort and stiffness.
- Antioxidant properties, which protect the joint from oxidative damage [Giovannucci, Hanninen]
- Direct anti-apoptopic effects on chondrocytes reducing cartilage degeneration [Shen].
- Modulation of metalloproteinases which can thin cartilage via an ability to regulate extracellular matrix [Dahlberg, Mitchel, Brinckerhoff].
A wide variety of polyphenols and other phytochemicals have been subject to cell line, animal and human experiments to help protect chondrocytes from environmental an physical damage and improve joint health. The evidence for many of these have been summaried in an Arthritis Research review [Aeuk]. In general plant foods which are colourful, tasty and have a nice auoma are rich in polyphenols such as herbs, spices, teas, fruit and vegetables but those with the most robust data include rosehip, turmeric (curcumin); green tea; boswellia serrate, cordyceps militaris, pomegranate; and broccoli and their studies are summarised in the nutritional supplement section below. In the mean time here are some recipes which embrace the anti-inflammatory high polyphenol, high plant protein philosophy:
Specific foods and food supplements.
A large number of studies have evaluated whether concentrating whole foods into a nutritional capsule enhance their anti-arthralgia effects [Shen]. Most of these studies have involved small number of people, not randomised so have been underpowered. Despite this over the counter (OTC) nutritional supplements are particularly popular amongst people with arthritis with formal surveys reporting that up to 60% of arthralgia suffers have tried a variety of products at one stage in their illness [Bishop]. The charity Arthritis Research has comprehensively reviewed 30 available OTC nutritional supplements, highlighting their potential benefits but emphasizing the significant gaps in research [Arthritis research, Shen, Kikuchi]. The more commonly used or potentially beneficial supplements are summarised below:
Glucosamine is an amino sugar made from shellfish or prepared in the laboratory has been found in animal studies to delay the breakdown, and improve repair, of damaged cartilage [Fox, Towheed]. In humans, with established arthritis, the results from 13 RCT’s are mixed, with a few demonstrating an improvement over placebo [Towheed]. A RCT involving 400 women with breast cancer and did demonstrate a significant difference in pain and knee joint space [Bruyere]. However, two large meta-analysis concluded no meaningful benefit or change clinical joint aspects of glucosamine although suggested further research is needed [Wandel, Towheed].
Chondroitin, is a complex sugar found in cartilage usually made commercially from cows, pigs and sharks. Laboratory studies have found it can reduce the activity of enzymes that break down collagen in joints in addition to their anti-inflammatory properties [Thomas K]. In humans, some of the 22 RCT have demonstrated a benefit over placebo but two meta-analysis concluded that, no clinically meaningful benefits could be attributed to regular supplementation [Reichenbach, Wandel].
Fish oils have been reported to improve symptoms of rheumatoid arthritis, and also enable lower non-steroidal intake; this in turn lowers the risks of their long-term intake particularly cardiovascular, renal and gastric disease. Evidence of a benefit for the use of fish liver oil for osteoarthritis lacks sufficient data [Cleland 2006, Fortin 1995]. A recent RCT involving women taking aromatase inhibitors found no benefit over placebo [Hershman 2015]
Rose hip (Rosa canina), a species of wild rose native to some regions in Europe, Africa and Asia contains vitamin C, is rich in the anthocyanin and flavonoids (quercetin and catechin) such as well as the galactolipids [Thomas]. Rosehip demostrated anti-inflammatory activities in several experimental models [Deliorman, Winther]. The anti-inflammatory mechanism of the polyphenols within rosehip have been demonstrated to be via their interaction with arachidonic acid metabolism and inhibition of both cyclooxygenase-1 and 2 [Lattanzio]. Rosehip has also been found to confer chondroprotective effects in vitro [Schwager]. Its clinic effect on joint health has been highlighted in two systemic reviews [Rossnage lK, Chrubasik C]. These included 4 clinical studies, which although small, suggest a meaningful benefit in humans. After 4 month intake of about 4 g a day, compared to versus placebo there were reductions in joint swelling, painkiller use. However, in view of the small numbers (80-100) an that not all trial demonstrated a benefit further studies are recommended.
Turmeric (Curcuma longa) is a perennial plant native to southern Asia originating from the ginger family. Its constituents include the three curcuminoids: curcumin (diferuloylmethane) the primary constituent and the one responsible for it’s vibrant yellow colour, demethoxycurcumin and bisdemethoxycurcumin, as well as volatile oils (tumerone, atlantone and zingiberone)[Thomas]. Pharmacological activities, including antioxidant and antimicrobial properties, have been attributed these curcuminoids, as they are highly pleiotropic molecule capable of interacting with numerous molecular targets involved in inflammation [Handler, Thomas]. Cell culture and animal research trials indicate that curcuminoids may have a role in diseases such as inflammatory bowel disease, pancreatitis and chronic anterior uveitis [Jurenka 2009]. In addition to these mechanisms, turmeric has anti-oxidant properties [White] which influences chondrocytes and peri-articular joint destruction [Jurenka].
In the most notable animal experiment, turmeric was administered on a 1:1 random basis intraperitoneally to rats prior to the onset of streptococcal cell wall-induced arthritis. The turmeric profoundly inhibited joint inflammation and periarticular joint destruction, in a dose-dependent manner. It also prevented local activation of NF-kappaB and the subsequent expression of NF-kappaB-regulated genes which mediate joint inflammation and destruction via including chemokines, cyclooxygenase 2 and RANK. Consistent with these findings, inflammatory cell influx, joint levels of prostaglandin E(2) and peri-articular osteoclast formation were inhibited by the turmeric extract treatment [Funk].
In humans, a crossover double blind RCT gave 50mg of turmeric in combination with zinc complex (50 mg/capsule), as well as other botanicals such as Boswellia serrate or placebo to 42 patients with osteoarthritis three times daily for three months. Participants then, crossed over for a further three months. Those taking the turmeric combination demonstrated significant improvements in pain severity and disability scores [Kulkarni]. Another study, involving 100 men and women with a history of joint pain were randomized participants to a placebo or a supplement containing turmeric root extract and a number of other extracts including: glucosamine sulfate; methylsufonlylmethane; white willow bark extract; ginger root concentrate; boswella serrate; cayenne; and hyaluronic acid. They reported an improvement in joint pain severity, improvements in the ability to perform daily activities and stiffness scores and knee pain after 8 weeks [Nieman]. Finally, a further study involving 107 participants with arthritic pains of the knee randomly compared 2 g turmeric versus 800mg ibuprofen per day, for 6 weeks. Although both groups’ pain levels improved when walking and climbing stairs it was significantly greater degree in the turmeric group [Kuptniratsaikul]. These and other studies have reported minimal adverse events even with intake over 3g/day [Shah, Sharma, Loa].
Green tea (Camellia sinensis) is a rich source of the catechins class of polyphenols, 60% of which constitutes epigallocatechin 3-gallate (EGCG) [Thomas, Manning, Cooper R]. EGCG has potent antioxidant activities, 25 times more than vitamins C, for example [Doss, Cooper]. A number of laboratory studies, using chondrocytes derived from OA cartilage, have demonstrated that pre-incubation with tea extract, or pure EGCG, reduced pro-inflammatory cytokines such as IL-1β, TNFα, IL-6, prostaglandin E2 and COX-2 when exposed to oxidative stress [Ahmed, Singh, [Samuels, Malemud]. Tea catechins, via their influence on inflammatory cytokins, block activation of matrix-degrading enzymes, termed matrix metalloproteinases (MMPs) [Ahmed-5, Brinckerhoff CE, Adcocks, Vankemmelbeke]. MMPs are a large group of collagenase enzymes expressed in high levels in arthritic joints, and involved in the turnover, degradation, and catabolism of extracellular joint matrix [Dahlberg, Mitchel] a subgroup of enzymes. Under normal circumstances, chondrocytes in the cartilage make extracellular matrix components, such as aggrecan and type II collagen, as required in response to mechanical pressure [Samuels]. Under condition of high oxidative stress related to an adverse diet or diseased conditions, however, chondrocyte metabolism is altered under the influence of the increased influx of pro inflammatory cytokines, which then activate MMP’s which promote cartilage degradation [Brinckerhoff, Goo].
In animals, the potential modifying effect of EGCG on arthritis was first discovered in a study in which the consumption of EGCG-containing GTE in drinking water ameliorated collagen-induced arthritis (CIA) in mice [Haqqi]. The reduced CIA incidence and severity was reflected in a marked inhibition of the inflammatory mediators COX-2, IFNγ, and TNFα in arthritic joints of green tea-fed mice. Additionally, total immunoglobulins (IgG) and type II collagen-specific IgG levels, were found to be lower in serum and arthritic joints of green tea-fed mice [Haqqi]. Despite this cell line and animal data there are no significant, adequately powered prospective trial data in humans with arthritis although studies investigating other conditions in humans have confirmed an excellent safety profile [taylor, Heck, Salahuddin, Cooper].
Pomegranate (Punica granatum L) is a ubiquitous tree fruit grown in hot dry countries. In the past decade, numerous studies on the antioxidant, anti-carcinogenic and anti-inflammatory properties of pomegranate constituents have been published, focusing on the treatment and prevention of cancer; cardiovascular disease; diabetes; dental conditions; male infertility; Alzheimer’s disease, arthritis; and obesity [Jurenka]. It contains a variety of phytochemicals including the antioxidant, punicalagin, and the polyphenol, gallic acid. One study demonstrated that pomegranate possesses significantly greater antioxidant capacity at much lower concentrations (>1000-fold dilutions) than either grape or blueberry juice, which was attributed to the higher anthocyanin flavonoid and higher total flavonoid content than the other juices [Ignarro]. These are further enhances by using the whole fruit, as there synergistic actions of the all pomegranate constituents, over that which is provided by single or extracted individual chemical constituents [Lansky]. In animal and in vitro studies, whole fruit pomegranate extract has been shown to inhibit both lipoxygenase and cyclooxygenase enzyme which are key to the conversion of inflammatory mediators arachidonic acid to prostaglandins [Schubert].
Another in vitro studies, pomegranate had a significant inhibitory effect on MMPs within arthritic joints, inhibited IL-1beta- induced destruction of proteoglycan as well as phosphorylation and activation of mitogen-activated protein kinases [Ahmed]. In humans, no randomised trials specifically investigating joint health have been performed but small pilot study demonstrated that pomegranate extract reduced joint tenderness and participants had lower serum markers of oxidative stress [Balbir-Gurman].
Broccoli is a cruciferous vegetable rich in phytochemical chemicals, such as isothiocyanate and its’ metabolite sulforaphane (SFN), and these have been found to have significant health benefits ranging from cancer, artherosclerosis and a variety of inflammatory disorders [ Thomas, Juge, Dinkova-Kostova, Zakkar]. Brocolli phytochemicals are thought to exert their influence via a variety of biochemical mechanisms. Firstly, they are known to be potent inductors of antioxidant enzymes, particularly glutathione which binds free radicals formed by dietary or environmental carcinogens before they damage our DNA, including those within the tissues of our joints [Moore LE et al 2007, Cornelis MC 2007). Secondly, SFN is a potent inducer of the factor NF-E2– related transcription factor 2 (Nrf2), which binds to an antioxidant response element in cognate genes [Juge N, Dinkova-Kostova AT, Brandenburg LO]. More relevant for joint health, SFN has been shown to modulate MMP expression in chondrocytes cell lines [Megias J, Kim HA, Kong JS, Young D]. In animal models of arthritis, mice fed an SFN-rich diet had significantly reduced cartilage destruction at 12 weeks, compared with those fed a control diet via a reduction in the activation and production of interleukin-17 and tumour necrosis factor [Chen WP, Culley, Kong JS]. Another recent animal study, lead by the School of Biological Sciences and Norwich Medical School, found that sulforaphane blocked histone deacetylase (HDAC) inhibitor as well as MMP expression which resulted in direct chondroprotective effects [Davison]. It has been reported that (HDAC) has chondroprotective properties [Young].
Cordyceps militaris, a parasitic caterpillar fungus found in humid tropical countries, is rich in the phytochemical cordycepin, also known as 3-deoxyadenosine a nucleoside derivative [Won]. Various studies have focused on the pharmacological activities of cordycepin and revealed it exerted properties, such as anti-inflammatory, anti-angiogenesis, anti-aging and anti-proliferation [Kim, yoo, lee, lee, rao]. Moreover, an in-vitro study has found that cordycepin inhibited expression of MMP-1 and MMP-3 in interleukin-1 beta (IL-1β) induced rheumatoid arthritis (RA) synovial fibroblasts [Noh]. A more recent study, examined the inhibitory effects of cordycepin on IL-1β induced osteoarthritis (OA) synovial fibroblasts. They discovered that cordycepin protected cartilage via its ability to decrease glycosaminoglycan (GAG) release, which prevents aggrecan degradation and proteoglycan loss, both are hallmark manifestations of OA. This study also highlighted a number of other properties of cordycepin which could potentially lead to the prevention of OA including inhibiting the gene expressions of MMP catabolic enzymes, cathepsin, and inflammatory mediators, such as Cyclo-oxidase-2 in a dose-dependent manner [Penfei]. Studies involving human cartilage and chondrocytes have confirmed cordycepin decreases GAG release, lowers nitric oxide production as well as gene expressions of inflammatory and catabolic mediators [Rao]. Despite what it does to caterpillars in the wild, extract of have been found to be completely safe in toxicology studies [Yan. Yooh]
Boswellia serrate (Indian Frankincense) is a branching tree of the family Burseraceae that grows in dry mountainous regions of India, Northern Africa and Middle East. Its resin contains a number of phytochemicals including monoterpenes, diterpenes; triterpenes; pentacyclic triterpenic acids (boswellic acids) and tetracyclic triterpenic acids [Siddiqui]. These phytochemicals, particularly the boswellic acids have wide range of microbiological effects which have potential disease modifying effects on the arthritis and other chronic conditions [Siddiqui].
In human chondrocytes, Boswellia serrata has demonstrated an ability to suppress a protein known as RANKL which induces osteoclastogenesis and potentiates apoptosis both preventing cartilage and bone reabsorption [Sengupta, Tardaka]. Boswellia has also been shown to suppress the TNF-α induced release of MMP-3 [Siddiqui, Sengupta]. A unique property of boswellic acid is its ability to inhibit leukotriene synthesis by interacting directly with or blocking translocation of the pro-inflammatory enzyme 5-lipoxygenase (5-LO) without effecting arachidonic acid [Siemoneit]. Finally, Boswellia serrata inhibits NF-kB activation from irritants such as cigarette smoke, okadaic acid which trigger TNF-α and IL-1β release or indeed direct exposure the these cytokines themselves [Siddiqui].
In mice with formaldehyde induced arthritis, those feed with Boswellia exhibited a >50% anti-arthritic activity both in terms of preventing arthritis development as well as those with established disease [Singh]. A similar protective effect was seen in rabbits who had arthritis induced by bovine serum albumin [Sharma].
In humans, a RCT involving 75 participants with established osteoarthritis found that, compared to placebo, those given enriched Boswellia serrata extract had improved pain and functional ability scores as well as significant reduction in synovial fluid matrix metalloproteinase-3 [Sengupta]. In another small RCT, 333 mg of Boswellia capsules three times a day for 8 weeks improved pain, knee flexion and walking distance compared to placebo [Kimmatkar]. The same dose was investigated in another trial RCT, this time involving 66 people for 6 months compared to the non-steroidal anti-inflammatory drug (NSAI) valdecoxib. Although pain, stiffness and ability to perform physical activity improved in all participants, the onset of action was slower in participants who were given boswellia. At the end of the trial, those in the Boswellia group experienced a significant less arthritic compared to those given the NSAI with an absolute magnitude of 15%, enough to improve joint related quality of life score [Sontakke]. Other smaller and non controlled randomised trials also involving participants with rheumatoid arthritis report similar benefits [Kulkarni, Chrubasik, Chopra].
Beetroot (Beta vulgaris rubra) is rich in several bioactive compounds including ascorbic acid, carotenoids, phenolic acids and flavonoids but is also one of the few vegetables that contain a group phytochemical pigments known as betalains. These are categorised as either betacyanin pigments that are red-violet in colour or betaxanthin pigments that are yellow-orange in colour [Clifford, Ninfali]. A number of investigations have reported betalains to have high antioxidant and anti-inflammatory capabilities in vitro and via a variety of in vivo animal models [Vidal, Clifford, Reddy]. This suggests beetroot may have a role in the nutritional management of clinical pathologies characterised by oxidative stress and chronic inflammation including arthritis [Pietrzkowski] and even cancer [Das].
The anti-inflammatory effects of betalains are mediated by interfering with pro-inflammatory signaling cascades involving Nuclear Factor-Kappa B (NF-κB) and interleukin-6 (IL-6) [Baker]. Betalains have also been shown to markedly suppress cyclooxygenase-2 (COX-2) expression in vitro, a precursor molecule for pro-inflammatory arachidonic acid metabolites and prostaglandins [Vidal]. One study group reported betanin inhibited COX-2 enzyme activity by 97%, a level comparable or greater than commonly used anti-inflammatory drugs (Ibuprofen, and Celebrex). In humans, therapeutic administration of betalain-rich oral capsules made from beetroot extracts alleviated inflammation and pain in osteoarthritic patients. In addition, after 10 days of supplementation (100, 70 or 35 mg per day), the pro-inflammatory cytokines; tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), had decreased from baseline by up to 30% [Pietrzkowski].
The antioxidant properties of betalain, and other pigments in beetroot, have been reported in several animal models in which numerous cellular elements are directly protected from toxic exposure from oxidative injury [Reddy, Clifford]. For example, in one study, rats were randomize to a normal diet or a diet supplemented with a dried beetroot extract for 7 days prior to being exposed to the known carcinogen reactive oxygen species carbon-tetrachloride, a well-established carcinogen and reactive oxygen, nitrogen species (RONS) generator. Those rats pre-treated with the beetroot expressed significantly lower levels of lipid peroxidation a marker of oxidative damage. Furthermore, the beetroot extracts fed rats maintained endogenous antioxidant enzyme activity (glutathione peroxidase, superoxide dismutase and catalase enzymes) at normal cellular concentrations following the oxidative insult which significantly dropped in the controls. This suggests beetroot also exhibits indirect antioxidant effects via up regulation of the antioxidant defense mechanisms [Vulić].
As a source of plant nitrates, beetroot ingestion provides a natural means of increasing nitric oxide (NO). The mechanism for this starts with the microflora in the upper gut which convert nitrates to nitrates which are then metabolised to NO and other nitrogen oxides by a variety of reductase enzymes [Lundberg]. This process is further enhanced by vitamin C which also prevent its conversion to nitrosamines which have carcinogenic properties [Tannenbaum, Kim-Shapiro]. This also explains why nitrate containing vegetables, which also contain vitamin C, have no cancer risks but cured meats which have added nitrites do [Raphaeolle]. Beetroot is emerging as a potential natural strategy to prevent pathologies associated with diminished NO bioavailability such as those associated with abnormal endothelial function including hypertension, atherosclerosis, type 2 diabetes and dementia [Hobbs, Vanhatalo, Wootton-Beard, Presley]. Studies in humans have demonstrated that the NO generating properties of beetroot are responsible for improvements in cerebrovascular blood flow lower cognitive deficits [Presley, Bondonno] [90–92]. Several studies have now established beetroot supplementation as an effective means of enhancing athletic performance via improved muscle blood flow and absorption of free radicals produced by strenuous exercise [Bailey, Cermak, Vanhatalo, Lansley, Ormsbee].
Piperine (Piper nigrum and Piper longum, respectively) is a constituent of black pepper and long pepper. Studies have shown it increases the bioavaility of polyphenols following ingestion of other foods such as curcumin which is not particularly well absorbed on its own [Belcaro]. For example, in humans 20mg piperine given concomitantly with 2g curcumin increased serum curcumin bioavailability 20-fold [Shoba]. In another study, complexing curcumin with a phospholipid increased absorption 5-fold [Belcaro]. It has also been shown to increase to absorption of polyphenols from other foods [Belcaro].