Omega-3 Fatty Acids
Omega-3 fatty acids help reduce inflammation that contributes to dry eyes in Sjögren syndrome (Liu 2014; Lin 2014; Sargi 2013). In fact, treatment of dry eye with oral omega-3 fatty acids is included in the Sjögren Syndrome Foundation’s clinical practice guidelines (Vivino 2016).
A higher consumption of omega-3 fatty acids relative to omega-6 fatty acids may decrease chronic inflammation and has been associated with a significantly reduced risk of dry eye syndrome (Simopoulos 2016; Liu 2014). In a three-month placebo-controlled study, both fish and krill oil significantly reduced eye redness (an indicator of eye inflammation) in patients with dry eye. Krill oil conferred additional benefits including significantly reduced tear levels of a pro-inflammatory cytokine implicated in autoimmune disease activity. This may have been related to the antioxidant astaxanthin, which naturally occurs in krill oil (Deinema 2017).
Early evidence suggests eye drops containing omega-3 fatty acids may also be an effective option for managing dry eye. In a mouse model of dry eye, treatment with eye drops containing 0.2% omega-3 fatty acids led to improvements in corneal irregularities and decreased levels of inflammatory markers on the eye surfaces (Li 2014). In another animal study, topical treatment with a synthetic precursor of resolvin E1, a compound produced in the body through omega-3 fatty acid metabolism, reduced the inflammatory response, increased tear production, and maintained eye surface integrity in a study in mice with dry eye disease (Li 2010).
Gamma Linolenic Acid
Omega-6 fatty acids from animal fats and corn, soy, and seed oils can have pro-inflammatory effects in the body. However, the omega-6 fatty acid gamma linolenic acid (GLA) has anti-inflammatory properties. GLA is synthesized in the body from the essential omega-6 fatty acid linoleic acid. Substantial amounts of GLA can also be obtained from certain plant-based oils such as black current seed oil, borage oil, and evening primrose oil (Simopoulos 2016; Sheppard 2013; Kawamura 2011; Kapoor 2006; Kim, Yoo 2012).
A controlled trial assessed the effectiveness of supplemental GLA from black current seed oil combined with omega-3 fatty acids from fish oil in postmenopausal women with moderate-to-severe dry eye. Six months of supplementation with GLA and omega-3 fatty acids significantly reduced eye irritation symptoms, maintained smoothness of the eye surface, and decreased eye inflammation and pain (Sheppard 2013).
The benefits of GLA in dry eye may be due to its ability to raise the concentration of an important anti-inflammatory cell-signaling molecule in the tear film (Barabino 2003).
White Peony Extract
Peony glucosides are biologically active constituents from white peony (Paeonia lactiflora) root, a traditional Chinese medicinal herb. Studies indicate peony glucosides have anti-inflammatory, immune-regulating, and pain-relieving properties (Feng 2016; He 2011; Wang 2014). Peony glucosides have been used extensively for the treatment of autoimmune diseases, including Sjögren syndrome (Zhou 2016; He 2011; Feng 2016).
In a randomized, double-blind, placebo-controlled clinical trial, total glucosides of peony (600 mg three times daily for 24 weeks) improved salivary gland function and decreased blood concentrations of inflammatory cell-signaling molecules in primary Sjögren patients (Zhou 2016). A retrospective study compared peony glucosides with hydroxychloroquine sulfate for treatment of Sjögren syndrome. Peony extract increased salivary flow, improved tear production, and decreased levels of an inflammatory marker as effectively as hydroxychloroquine, but was associated with fewer severe adverse effects (Zhang 2007).
Animal studies suggest the anti-inflammatory effects of peony glucosides play a prominent role in its clinical benefits. In a mouse model of Sjögren syndrome, paeoniflorin, an active peony glucoside, was shown to alleviate inflammation in salivary gland epithelial cells (Li, Sun 2016). In another study in a mouse model of Sjögren syndrome, peony glucosides decreased the production of certain inflammatory cytokines (Wu 2016).
Lactoferrin is an iron-binding protein found in human milk and other body secretions including saliva and tears. Studies indicate oral supplementation with lactoferrin is an effective treatment option for dry eye diseases such as Sjögren syndrome (Devendra 2015; Pastori 2015; Dogru 2007). Low levels of lactoferrin in tears have been associated with increased severity of eye surface damage due to dry eye in patients with Sjögren syndrome (Danjo 1994).
Among its many functions, lactoferrin has antimicrobial and anti-inflammatory activity, promotes wound healing, and stimulates secretion of nerve growth factor. Lactoferrin can also protect cells and tissues against damage caused by oxidative stress (Vogel 2012; Pastori 2015; Dogru 2007).
In a controlled trial in Sjögren syndrome patients, treatment with oral lactoferrin resulted in significant improvement in tear film stability, eye surface lesions, and dry eye symptoms. These improvements diminished when treatment was discontinued (Dogru 2007). In another controlled trial, lactoferrin was shown to alleviate dry eye symptoms postoperatively in cataract surgery patients (Devendra 2015).
Vitamin D modulates the immune system and suppresses autoimmunity (Erten 2015; Baldini 2014; Arnson 2007). Vitamin D deficiency has been strongly associated with dry eye and impaired tear function (Demirci 2016; Yildirim 2016). Vitamin D supplementation has been shown to effectively treat dry eye, and may protect against complications of Sjögren syndrome (Bae 2016; Agmon-Levin 2012).
One study found that women, but not men, with Sjögren syndrome had significantly lower vitamin D levels than healthy controls (Erten 2015). In another study, Sjögren-related peripheral neuropathy and lymphoma were more common in those with low vitamin D levels (Agmon-Levin 2012).
In an observational study, patients with dry eye syndrome resistant to conventional treatment were given a single intramuscular injection of 200,000 IU of vitamin D3. Ten weeks after the injection, dry eye symptoms were reduced, tear secretion was enhanced, and inflammation at the eye surface and eyelid margin was decreased (Bae 2016).
N-acetylcysteine (NAC) is an amino acid-based compound used in conventional medicine as a mucous-thinning agent. NAC is a precursor to glutathione, an important detoxifying molecule in the body that protects cells against oxidative injury (Rushworth 2014).
In Sjögren syndrome, NAC has been used to stimulate saliva flow and tear secretion in the management of dry eyes and mouth (Ramos-Casals 2012). In a double-blind crossover trial, treatment of Sjögren patients with 200 mg NAC three times daily resulted in considerable improvement in mouth and eye dryness. Damage to the eye surface was also improved (Walters 1986).
Maqui Berry Extract (Aristotelia chilensis)
Maqui berry (Aristotelia chilensis) is a tropical berry rich in anthocyanin pigments, which give the berries a dark red or purple color (Watson 2015). In its native Chile, maqui berry has been used for centuries as a traditional medicine to promote wound healing and improve stamina and strength (Romanucci 2016).
In a trial of 13 subjects diagnosed with moderately dry eyes, treatment with either 30 mg or 60 mg maqui berry extract resulted in substantial improvement in tear fluid volume within 30 days. After 60 days of treatment, improvement was sustained in those receiving 60 mg per day, with a nearly 48% increase in tear production compared with baseline, but had diminished slightly in those receiving 30 mg per day. A substantial improvement in dry eye-related quality of life score—a patient-reported measure of eye function, comfort, and symptoms—was also reported in the 60 mg group (Hitoe 2014).
Changes in composition and diversity of the human microbiomeautoimmune diseases (Belkaid 2014; McLean 2015; Karczewski 2014). Ingestion of probiotics improves microbiome health and may modulate autoimmunity (Chae 2012; Hemarajata 2013; de Sousa Moraes 2014; de Oliveira 2017).
Bacteria not only colonize the lining of the intestine, but other mucosal surfaces as well, including those of the mouth and eye (Karczewski 2014; Li, Zou 2016; Terzulli 2015). One study found that the oral microbiome in Sjögren patients differed from that of healthy controls, and was less diverse (Li, Zou 2016).
Sjögren patients with dry mouth have an increased risk for dental caries, periodontal disease, halitosis (bad breath), and oral candidiasis (thrush) (Rischmueller 2016). In a double-blind placebo-controlled trial, administration of lozenges containing the probiotic Streptococcus salivarius strain BLIS M18 over a three-month period significantly reduced formation of dental plaque in children with dental caries. A subgroup of children who demonstrated the most effective bacterial colonization also exhibited reduced counts of Streptococcus mutans, a bacterium that contributes to tooth decay (Burton 2013).
Probiotic lozenges containing Streptococcus salivarius strain BLIS M18 have also been shown in a study in adults to be effective in reducing moderate-to-severe gingivitis and moderate periodontitis (Scariya 2015). A review of studies concluded that oral probiotics are a promising emerging intervention for the treatment and prevention of oral diseases (Saha 2012).
Green Tea Extract
Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol component of green tea (Camellia sinensis) leaves. Animal preclinical studies indicate EGCG has preventive and therapeutic potential in Sjögren syndrome (Dickinson, DeRossi 2014; Dickinson, Yu 2014; Cavet 2011; Ohno 2012; Gillespie 2008). In an animal study, EGCG effectively protected mouse salivary glands from autoimmune-induced inflammation (Gillespie 2008).
Levels of three important enzymes that counteract cell damage caused by free radicals are decreased in affected glandular tissues in Sjögren patients. Findings from preclinical studies suggest EGCG may help restore these enzyme levels (Dickinson, DeRossi 2014).
Resveratrol is a plant polyphenol with anti-inflammatory, oxidative stress-reducing, and immune-modulating effects. Results from animal studies show resveratrol can have beneficial effects in immune-mediated conditions, including Sjögren syndrome (Inoue 2016; Svajger 2012).
In a study on mice with impaired salivary gland function, resveratrol significantly increased secretion of saliva compared with the control group. Enhanced production of an anti-inflammatory cytokine in the salivary glands of the resveratrol-treated mice appeared to have contributed to the beneficial results (Inoue 2016).
Iron, Vitamin B12, and Folic Acid
Iron and vitamin deficiencies frequently occur in individuals with primary Sjögren syndrome. In a study in Sjögren patients, over half of participants had an iron deficiency, and a significant portion of participants had vitamin B deficiencies. These nutrient deficiencies can affect the function of the salivary and lacrimal (tear) glands, as well as the immune system (Lundstrom 2001).
Vitamin B12 deficiency in Sjögren syndrome results primarily from malabsorption of this vitamin. This inability to absorb B12 (as well as iron and folate) is related to low stomach acid and/or gastritis, common manifestations of Sjögren syndrome (Andres 2001; Kim-Lee 2015; Kines 2016; Sugaya 1995; Maury 1985).
Low blood levels of vitamin B12 and folate are associated with elevated plasma levels of homocysteine. High homocysteine levels promote neurodegeneration and increase risk of cardiovascular disease (Stanger 2009; Ganguly 2015). Early detection of these nutrient deficiencies and repletion with appropriate oral supplementation may prevent potential serious complications and protect the overall health of people with Sjögren syndrome (Andres 2001).
Vitamin B12 and Folate Deficiencies in Sjögren Syndrome: Cardiovascular and Cognitive Risks
Deficiencies of vitamin B12 and folate are common in people with Sjögren syndrome (Lundstrom 2001). A deficiency of these B vitamins can lead to elevated blood levels of homocysteine—a molecule that is toxic to the inner arterial lining and significantly increases cardiovascular disease risk. Increased homocysteine levels also trigger damage to the nervous system, and have been linked to cognitive impairment, dementia, depression, and Alzheimer and Parkinson disease (Ganguly 2015; Mao 2016; Wright 2008).
High plasma concentrations of homocysteine have been associated with various diseases of the eye, including dry eye (Wright 2008; Sekeryapan 2013). In one study, elevated plasma homocysteine was detected in nearly 44% of dry eye patients compared with approximately 33% of controls (Sekeryapan 2013). In a study in patients with primary open-angle glaucoma, participants who also had dry eye disease had significantly higher homocysteine levels in tears and blood than those without dry eye disease (Roedl 2008).
Vitamin B12 and folate have been shown to reduce homocysteine levels (Ganguly 2015; Wright 2008). In an analysis of a major stroke prevention trial, the risk of stroke, heart attack, and death decreased by 24% in stroke survivors older than 67 years who were given high-dose vitamin B12 injections to lower homocysteine levels (Towfighi 2014). This finding of greater benefit from homocysteine-lowering therapy in older individuals in consistent with the fact that damage to the arterial lining may sometimes take decades to eventually manifest as overt vascular disease (NIH 2016b; Funk 2012; Vita 2005). People with Sjögren syndrome should strive to maintain good vascular health, as vascular inflammation due to primary Sjögren syndrome may be a risk factor for ischemic stroke (Yang 2016).
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