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Autoimmune conditions

Everything in the library studied for it, medical and holistic together. Within each kind, what was shown to help comes first, strongest evidence first. What was tested and not shown to help stays on the list.

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Medication4 Supplements21 Practices5 Diets1 Lab markers3

Medication

Oral corticosteroidsStrong

Rheumatoid arthritis

Shown to ease joint tenderness and pain in rheumatoid arthritis more than placebo or NSAIDs, and to slow joint damage on X-ray over 1 to 2 years.

The numbers and sources

Effect: Low-dose prednisolone, at no more than 15 mg a day, improved joint tenderness against placebo by 12 tender joints (95% CI 6 to 18) and improved pain (SMD 1.75, 95% CI 0.87 to 2.64) and grip strength. Against NSAIDs it improved joint tenderness by 9 joints (95% CI 5 to 12) and pain (SMD 1.25, 95% CI 0.26 to 2.24) [4]. Across 15 studies, mostly in early disease and added to other disease-modifying drugs, glucocorticoids slowed X-ray progression (SMD 0.40, 95% CI 0.27 to 0.54), with a similar effect at 2 years (0.42, 95% CI 0.30 to 0.55) [5]. In a 2-year trial of prednisone 10 mg a day, clinical improvement over placebo was seen mainly in the first 6 months and X-ray progression was lower after month 6, with more osteoporotic fractures in the prednisone group [6].
Population: 320 people with rheumatoid arthritis in 10 short-term studies [4]; 1,414 people in 15 studies [5]; people with early active rheumatoid arthritis not yet on disease-modifying drugs [6].
Sources: [4], [5], [6]
Caveats: The short-term review covers small trials [4]. The mean cumulative dose in the X-ray studies was 2,300 mg of prednisone equivalent in the first year [5].

Low-dose naltrexoneLimited

Crohn's disease

Small trials found more clinical and endoscopic responses than placebo in Crohn's disease, while remission did not differ significantly. Evidence was rated low quality.

The numbers and sources

Effect: A Cochrane review found 2 RCTs (46 participants). In 34 adults, 4.5 mg a day for 12 weeks led to clinical remission in 30% against 18% on placebo (RR 1.48, 95% CI 0.42 to 5.24). A 70-point clinical response occurred in 83% against 38% (RR 2.22, 95% CI 1.14 to 4.32), and endoscopic response in 72% against 25% (RR 2.89, 95% CI 1.18 to 7.08). Endoscopic remission did not differ significantly [9].
Population: 34 adults with active Crohn's disease and 12 children [9].
Sources: [9]
Caveats: The review rated the evidence as low quality because of sparse data and found it insufficient for firm conclusions [9].

Low-dose naltrexoneLimited

Multiple sclerosis

Small trials found mixed results in multiple sclerosis: one saw better mental health and pain scores, another no difference from placebo.

The numbers and sources

Effect: In a crossover trial of 80 people, 4.5 mg nightly for 8 weeks raised the SF-36 mental component score by 3.3 points (p 0.04) and the Mental Health Inventory by 6 points (p < 0.01), and improved pain effects by 1.6 points (p 0.04) [10]. In a 17-week crossover trial of 96 people, pain, energy, emotional well-being, cognitive function and overall quality of life did not differ from placebo [11].
Population: Adults with relapsing-remitting or secondary progressive multiple sclerosis, 80 at one center [10] and 96 at two universities [11].
Sources: [10], [11]
Caveats: Only 60 of 80 completed the first trial, and its authors state dropouts and data errors cut its statistical power [10]. Neither trial measured relapses or disability as a main outcome.

Low-dose naltrexoneLimited

Other autoimmune conditions

One trial found no change in disease activity over placebo in lichen planopilaris, a scarring hair loss. No trials in other autoimmune conditions were located.

The numbers and sources

Effect: In 34 patients with lichen planopilaris, an autoimmune scarring hair loss, 3 mg a day added to clobetasol cream for 6 months did not change disease activity more than placebo with clobetasol (p 0.813) [13].
Population: 34 patients analyzed by intention to treat [13].
Sources: [13]
Caveats: One small trial in one condition. No controlled trials in lupus, rheumatoid arthritis, psoriasis or thyroid disease were located.

Supplements

Thunder god vineCautionStrong

Rheumatoid arthritis

Shown to improve joint swelling, stiffness and grip in adults with rheumatoid arthritis, matching or beating standard drugs, in trials mostly from China.

The numbers and sources

Effect: Across 14 RCTs, TwHF extracts improved grip strength, swollen joint count and morning stiffness against placebo (P < 0.001). Against DMARDs, grip strength, morning stiffness, CRP and tender joint count differed (P < 0.05), and ESR and swollen joint count did not [1]. Across 40 RCTs (3,092 patients), tripterygium glycosides added to DMARDs lowered morning stiffness, tender and swollen joint counts, pain scores, CRP, ESR and rheumatoid factor against DMARDs alone (all p < .001) [2]. A network meta-analysis of 21 trials (5,039 participants) ranked TwHF with methotrexate first and TwHF alone second for ACR20 response among the conventional DMARDs compared [3]. In 207 patients, ACR50 response at 24 weeks was 46.4% on methotrexate, 55.1% on TwHF (p 0.014) and 76.8% on both (p < 0.001) [4]. In 121 US patients, 65.0% on TwHF extract and 32.8% on sulfasalazine met ACR20 at 24 weeks (P 0.001) [5].
Population: Adults with active rheumatoid arthritis, mostly in China [1][2][3][4]. 121 patients at US centers [5].
Sources: [1], [2], [3], [4], [5]
Caveats: The methotrexate trial was open label, with blinded assessors [4]. In the sulfasalazine trial only 62 patients had outcome data at 24 weeks, and 62% and 41% stayed on treatment [5]. Most pooled trials were small and Chinese.

TurmericStrong

Rheumatoid arthritis

Shown to lower disease activity, joint counts and inflammation markers in adults with rheumatoid arthritis, in few small trials with very low certainty.

The numbers and sources

Effect: Across 6 publications (539 patients), curcumin lowered DAS28 (MD -1.20, 95% CI -1.85 to -0.55), ESR (MD -29.47), swollen joint count (MD -5.33) and tender joint count (MD -6.33) against controls [19]. Across 7 RCTs, DAS28 fell by 1.47 (95% CI -1.68 to -1.26), with lower rheumatoid factor, ESR and CRP [20]. Across 6 placebo-controlled trials (244 participants), ACR20 response, DAS28, ESR, CRP, pain and joint counts all improved, with very low certainty for most outcomes [21].
Population: Adults with rheumatoid arthritis [19][20][21].
Sources: [19], [20], [21]
Caveats: The trials were few and small, heterogeneity was substantial [20], and the certainty of evidence was very low [21].

TurmericStrong

Ulcerative colitis

Shown to raise clinical remission about twofold added to standard treatment in adults with ulcerative colitis. Reviews differ on endoscopic remission.

The numbers and sources

Effect: Across 8 RCTs (482 patients), curcumin added to standard treatment raised clinical remission against placebo (RR 2.33, 95% CI 1.25 to 4.34, I² 80%). Endoscopic remission did not differ significantly (RR 4.17, 95% CI 0.63 to 27.71) [22]. A meta-analysis of 6 RCTs (385 participants) found more clinical remission (RR 2.10, 95% CI 1.13 to 3.89) and no significant difference in endoscopic remission [23]. Another of 6 RCTs (349 patients) found more clinical remission (OR 5.18, 95% CI 1.84 to 14.56) and endoscopic remission (OR 5.69, 95% CI 1.28 to 25.27) with curcumin added to mesalamine [24].
Population: Adults with ulcerative colitis, mostly on mesalamine [22][23][24].
Sources: [22], [23], [24]
Caveats: Heterogeneity was high and the trials overlap across the reviews [22]. Some trials gave curcumin as an enema rather than by mouth [24].

Vitamin DStrong

Rheumatoid arthritis disease activity

Shown to lower disease activity modestly in adults with rheumatoid arthritis. Reviews disagree on CRP, ESR and pain.

The numbers and sources

Effect: Across 6 studies (438 patients), vitamin D lowered DAS28 (WMD -0.41, 95% CI -0.59 to -0.23), ESR (WMD -3.40) and tender joint count (WMD -1.44) against control [6]. Across 11 RCTs, it lowered pain scores (WMD -1.30) and DAS28-CRP (WMD -0.58, 95% CI -0.86 to -0.31), while CRP, ESR and HAQ did not change [7]. A third meta-analysis of 11 studies found lower DAS28 (WMD -0.83, 95% CI -1.38 to -0.28), CRP and ESR, with no change in HAQ or pain scores [8].
Population: Adults with rheumatoid arthritis in RCTs [6][7][8].
Sources: [6], [7], [8]
Caveats: The reviews disagree on CRP, ESR and pain, and heterogeneity was high [7].

Fish oilModerate

Lupus disease activity

Shown to lower lupus disease activity about 0.9 SLEDAI points at 3 g a day or less in adults with lupus, at low certainty.

The numbers and sources

Effect: Across 5 RCTs (274 patients), omega-3 at 3 g a day or less reduced lupus disease activity (SMD -0.33, 95% CI -0.57 to -0.09), about 0.9 SLEDAI points (95% CI -1.6 to -0.3) [25]. A systematic review of 13 trials found 8 of 10 that measured disease activity reported improvement. Kidney measures, C3, C4 and anti-dsDNA did not change [26].
Population: Adults with systemic lupus erythematosus, 80% or more women, over 12 to 52 weeks [25][26].
Sources: [25], [26]
Caveats: The meta-analysis rated certainty as low [25]. The systematic review describes the evidence as conflicting [26].

ProbioticsModerate

Ulcerative colitis

Shown to raise remission in active ulcerative colitis over placebo, with low certainty. Effect on keeping remission was uncertain.

The numbers and sources

Effect: A Cochrane review of 14 studies (865 participants) found more clinical remission in active disease on probiotics than placebo (RR 1.73, 95% CI 1.19 to 2.54, 9 studies, 594 participants, low certainty, number needed to treat 5). Remission did not differ from 5-ASA (RR 0.92, 95% CI 0.73 to 1.16, 1 study) [20]. For keeping remission, a Cochrane review of 12 studies (1,473 participants) found it uncertain whether relapse differed from placebo (RR 0.87, 95% CI 0.63 to 1.18) and little or no difference from 5-ASA (RR 1.01, 95% CI 0.84 to 1.22) [21].
Population: Mostly adults with mild to moderate ulcerative colitis [20][21].
Sources: [20], [21]
Caveats: Risk of bias was high in all but two or three studies in each review, and certainty ranged from moderate to very low [20][21].

Vitamin DLimited

Preventing autoimmune disease

One trial found about 22% less autoimmune disease over 5 years in older adults, and the difference was gone 2 years after the trial ended.

The numbers and sources

Effect: In VITAL, 2,000 IU a day for a median 5.3 years led to confirmed autoimmune disease in 123 people against 155 on placebo (HR 0.78, 95% CI 0.61 to 0.99, P 0.05). The outcome counted rheumatoid arthritis, polymyalgia rheumatica, autoimmune thyroid disease, psoriasis and others [48]. Two years after the trial ended, the difference was gone (HR 0.98, 95% CI 0.83 to 1.17 at 7 years) [49].
Population: 25,871 US men 50 and older and women 55 and older, mean age 67.1 [48]. 21,592 followed for 2 more years [49].
Sources: [48], [49]
Caveats: Both sources are the same trial. Adding 65 newly confirmed cases from the randomized period changed the HR to 0.85 (95% CI 0.70 to 1.04) [49]. Participants were not selected for deficiency.
Why limited: This rests on one trial, of 25,871 people. Strength counts independent studies that agree, so one trial is limited at any size.

Fish oilModerate

Rheumatoid arthritis

Mixed results: one review found better disease activity markers in rheumatoid arthritis, while others found small or no effects on pain and swollen joints.

The numbers and sources

Effect: Across 20 RCTs (1,252 patients), omega-3 improved eight disease activity markers. Of five inflammatory markers, only leukotriene B4 fell (SMD -0.440, 95% CI -0.676 to -0.205) [11]. Across 23 placebo-controlled trials, pooled effects on pain (SMD -0.16, 95% CI -0.40 to 0.09), tender joints (SMD -0.20, 95% CI -0.46 to 0.05) and swollen joints (SMD -0.10, 95% CI -0.28 to 0.07) were small, with intervals that include no effect [12]. Across 18 RCTs (1,018 patients), tender joint count fell (SMD -0.59, 95% CI -0.79 to -0.39), while ESR, CRP and DAS28 did not change significantly [13].
Population: Adults with rheumatoid arthritis in RCTs [11][12][13].
Sources: [11], [12], [13]
Caveats: The certainty of the evidence was mostly very low or low [12]. The authors of [12] note that earlier findings of lower NSAID use may reflect inadequate blinding.

ProbioticsModerate

Rheumatoid arthritis

Mixed results: reviews agree probiotics lower CRP or IL-6 in rheumatoid arthritis, but disagree on disease activity.

The numbers and sources

Effect: Across 9 studies (361 patients), probiotics lowered IL-6 (SMD -0.708) and did not change disease activity scores (MD 0.023, 95% CI -0.584 to 0.631) [8]. Across 4 RCTs (153 participants), DAS fell (SMD -0.58, 95% CI -0.97 to -0.19), CRP fell borderline (SMD -0.32, 95% CI -0.65 to 0.00), and ESR and cytokines did not change [9]. A review of 8 RA trials (344 patients) found CRP 3.04 mg/L lower (95% CI -4.47 to -1.62). With high risk-of-bias trials excluded, DAS28 did not differ from placebo (SMD -0.54, 95% CI -1.94 to 0.85) [10].
Population: Adults with rheumatoid arthritis, mostly women, over 8 weeks to 1 year [8][9][10].
Sources: [8], [9], [10]
Caveats: The reviews agree on lower CRP or IL-6 and disagree on disease activity. Strains, doses and durations varied [10].

SeleniumModerate

Hashimoto's thyroiditis

Mixed results: thyroid antibodies fell in people with Hashimoto's in both reviews, while reviews disagree on whether TSH changed.

The numbers and sources

Effect: Thyroid peroxidase antibodies fell in both reviews. In people on levothyroxine, the weighted mean difference after 3 months was -271 (95% CI -366 to -175) [5]. Across 29 cohorts, the SMD was -0.96 (95% CI -1.36 to -0.56) [6]. On TSH, sources disagree. In people not on thyroid hormone, a 2017 review found no change in TSH, quality of life or ultrasound findings [7]. A 2024 review found TSH lower (SMD -0.21, 95% CI -0.43 to -0.02, 869 people) [6].
Population: Adults with chronic autoimmune thyroiditis, 16 trials [5], 9 trials [7] and 35 studies [6].
Sources: [5], [6], [7]
Caveats: Antibody levels are a lab marker. The 2016 review rated evidence quality low [5], and the 2024 review moderate, with I² of 90% for antibodies [6].

TurmericModerate

Psoriasis

Mixed results: one review reported lower psoriasis severity, but its confidence interval includes no effect. Small trials of oral and topical curcumin lowered severity.

The numbers and sources

Effect: A meta-analysis of 7 RCTs found curcumin alone or with other treatment improved PASI against controls (std. MD -0.83, p 0.02) [29]. In 63 patients with mild to moderate psoriasis on topical steroids, oral curcumin 2 g a day (Meriva) for 12 weeks lowered PASI more than steroids alone [30]. In 40 patients with scalp psoriasis, a topical turmeric tonic twice a day for 9 weeks lowered PASI and improved quality of life against placebo (P < .05) [31]. In an open trial without placebo, 4.5 g a day of oral curcuminoids gave a response rate of 16.7% (95% CI 2% to 48%) [32].
Population: Adults with plaque or scalp psoriasis [29][30][31][32].
Sources: [29], [30], [31], [32]
Caveats: The meta-analysis abstract gives a 95% CI of -1.53 to 0.14, which includes no effect, alongside p 0.02 [29]. The trials were small and mixed oral and topical forms. The open trial authors attribute its low response to placebo effect or natural history [32].

Vitamin DModerate

Multiple sclerosis

Mixed results: a Cochrane review found no change in relapses or disability in MS, while later analyses found modest drops in relapse and disability.

The numbers and sources

Effect: A Cochrane review of 12 RCTs (933 participants) found vitamin D3 did not change annualized relapse rate (rate difference -0.05, 95% CI -0.17 to 0.07), disability scores (EDSS MD -0.25, 95% CI -0.61 to 0.10) or MRI lesions at 52 weeks, from very low-quality evidence [33]. A later meta-analysis of 21 studies (1,903 patients) found lower EDSS (MD -0.17), fewer patients relapsing (OR 0.66) and fewer new T2 lesions, and no change in annualized relapse rate, fatigue or quality of life [34]. A network meta-analysis of 32 RCTs (2,254 patients) found lower relapse risk (RR 0.80) and EDSS (MD -0.22) with long-term supplementation [35]. In 316 people with a first episode typical of MS, 100,000 IU every 2 weeks for 24 months lowered disease activity (60.3% against 74.1%, HR 0.66, 95% CI 0.50 to 0.87), driven by MRI findings. Relapse did not differ (17.9% against 21.8%, HR 0.69, 95% CI 0.42 to 1.16) [36].
Population: Adults with MS, mostly on standard treatment [33][34][35]. Untreated adults with clinically isolated syndrome in France [36].
Sources: [33], [34], [35], [36]
Caveats: The Cochrane review and the later analyses disagree. The later analyses include more and newer trials, and their authors describe the effects as modest [34].

Vitamin DModerate

Inflammatory bowel disease

Mixed results: one review found about 36% fewer relapses in inflammatory bowel disease, mostly Crohn's in remission, while another found no change in relapse or activity.

The numbers and sources

Effect: Across 7 RCTs (458 patients), vitamin D lowered clinical relapse against placebo (RR 0.64, 95% CI 0.46 to 0.89). In Crohn's disease in remission the RR was 0.47 (95% CI 0.27 to 0.82), and ulcerative colitis had only 2 studies (67 patients) [37]. In adults, the Harvey Bradshaw Index for Crohn's disease fell by 1.47 points (95% CI -2.47 to -0.47) and hs-CRP fell by 1.58 mg/L [38]. A meta-analysis of 17 trials (1,127 patients) found lower CRP (SMD -0.33) and no change in disease activity (SMD -0.13, 95% CI -0.66 to 0.39) or relapse (RR 0.59, 95% CI 0.19 to 1.86) [39].
Population: Adults with Crohn's disease or ulcerative colitis [37][38][39].
Sources: [37], [38], [39]
Caveats: The reviews disagree on relapse. Evidence for ulcerative colitis is thin [37].

Vitamin DModerate

Lupus disease activity

Mixed results: an earlier review found no significant change in lupus activity, while later reviews found modestly lower activity in adults with lupus.

The numbers and sources

Effect: Across 5 RCTs (490 participants), SLEDAI disease activity scores did not differ significantly from placebo (SMD -0.507, 95% CI -1.055 to 0.041), and fatigue scores fell in 2 trials (SMD -1.179) [40]. Later meta-analyses found lower disease activity: SMD -0.54 across 10 RCTs (847 participants) [41], and SLEDAI MD -1 (95% CI -2 to -0.43) in a review of 21 studies [42].
Population: Adults with systemic lupus erythematosus [40][41][42].
Sources: [40], [41], [42]
Caveats: The earlier and later reviews disagree.

Fish oilLimited

Preventing autoimmune disease

One trial found autoimmune disease was not significantly lower on 1,000 mg a day over 5.3 years. Two more years of follow-up found 17% fewer cases.

The numbers and sources

Effect: In VITAL, 1,000 mg a day of marine omega-3 for a median 5.3 years led to confirmed autoimmune disease in 130 people against 148 on placebo (HR 0.85, 95% CI 0.67 to 1.08, P 0.19) [36]. With 2 more years of follow-up after the trial, the HR was 0.83 (95% CI 0.70 to 0.99), with 234 cases against 280 [37].
Population: 25,871 US men 50 and older and women 55 and older [36]. 21,592 followed for 2 more years [37].
Sources: [36], [37]
Caveats: Both sources are the same trial. The randomized result did not reach significance, and the later result includes cases after the trial ended [36][37].
Why limited: This rests on one trial, of 25,871 people. Strength counts independent studies that agree, so one trial is limited at any size.

Fish oilStrong

Crohn's disease and ulcerative colitis

Not shown to prevent relapse of Crohn's disease in the two large low-bias trials, or of ulcerative colitis.

The numbers and sources

Effect: A Cochrane review of 6 studies (1,039 patients) found 39% relapsed on omega-3 at 12 months against 47% on placebo (RR 0.77, 95% CI 0.61 to 0.98). In the two large low risk-of-bias trials (738 patients) it was 37% against 42% (RR 0.88, 95% CI 0.74 to 1.05) [14]. In those two trials, 4 g a day for up to 58 weeks did not change relapse at 1 year (31.6% against 35.7%, HR 0.82, and 47.8% against 48.8%, HR 0.90) [15]. In ulcerative colitis, 3 studies (138 patients) found relapse rates similar to placebo (RR 1.02, 95% CI 0.51 to 2.03) [16]. Across 13 RCTs in people with bowel disease, relapse had RR 0.85 (95% CI 0.72 to 1.01), from low-quality evidence [17].
Population: Patients with Crohn's disease in remission [14][15]. People with ulcerative colitis in remission [16]. Adults in trials of 24 weeks or more [17].
Sources: [14], [15], [16], [17]
Caveats: The Cochrane authors rated the pooled Crohn's result very low quality because of heterogeneity and publication bias [14]. The ulcerative colitis review had few patients [16].

Fish oilStrong

Psoriasis severity

Not shown to reduce psoriasis severity on its own in adults. Added to conventional treatment, PASI scores fell about 4 points.

The numbers and sources

Effect: Across 3 RCTs (337 participants) with usable data, fish oil did not reduce PASI (MD -0.28, 95% CI -1.74 to 1.19) [18]. A review of 18 RCTs (927 participants) found fish oil alone had no effect on PASI (P 0.47), lesion area or itch. Combined with conventional treatment, PASI fell by 3.92 points (95% CI -6.15 to -1.69) [19].
Population: Adults with psoriasis [18][19].
Sources: [18], [19]
Caveats: Only 3 of 13 trials had usable data in [18].

Vitamin DStrong

Psoriasis severity

Not shown to lower psoriasis severity with oral vitamin D in adults. One small pooled effect lost significance after adjustment.

The numbers and sources

Effect: Across 3 trials, oral vitamin D lowered PASI at 6 months (MD -0.92, 95% CI -1.72 to -0.11), and the result lost significance after Hartung-Knapp adjustment (95% CI -2.21 to 0.38) [9]. Across 4 studies (333 patients), PASI, DLQI and CRP changes did not differ from control [10]. In 122 adults in Norway with low vitamin D, 100,000 IU then 20,000 IU a week for 4 months did not change PASI against placebo (adjusted difference 0.11, 95% CI -0.23 to 0.45) [11].
Population: Adults with plaque psoriasis [9][10][11].
Sources: [9], [10], [11]
Caveats: Baseline severity was low in the Norwegian trial (mean PASI 3.1) [11]. This concerns oral vitamin D, not topical vitamin D analogue creams.

ProbioticsModerate

Crohn's disease

Not shown to bring or keep remission in Crohn's disease, in very small studies.

The numbers and sources

Effect: A Cochrane review of 2 studies (46 participants) found no difference from placebo in inducing remission after 6 months (RR 1.06, 95% CI 0.65 to 1.71, very low certainty) [22]. A Cochrane review of 7 small maintenance studies found no significant reduction in relapse with E. coli Nissle (RR 0.43, 95% CI 0.15 to 1.20) or Lactobacillus GG after surgery (RR 1.58, 95% CI 0.30 to 8.40) or medical treatment (RR 0.83, 95% CI 0.25 to 2.80) [23].
Population: Adults and children with Crohn's disease [22][23].
Sources: [22], [23]
Caveats: Studies were very small and could not be pooled for maintenance [23].

Alpha-lipoic acidLimited

Progressive multiple sclerosis

One trial found 1,200 mg a day did not slow walking decline over 24 months in progressive MS. Brain volume looked steadier than on placebo.

The numbers and sources

Effect: Over 24 months, 1,200 mg a day did not slow the decline in walking speed (-0.39 against -0.30 ft/s, difference -0.08, 95% CI -0.33 to 0.17). Mobility and patient-reported outcomes did not differ. Whole-brain and deep gray matter volume appeared stable on lipoic acid and declined on placebo [10].
Population: 115 people with primary or secondary progressive MS at 11 sites in the US and Canada [10].
Sources: [10]
Caveats: 37% on lipoic acid and 17% on placebo left the study [10].

Deer antler velvetLimited

Arthritis

One trial found elk velvet antler did not differ from placebo over 6 months in 168 adults with rheumatoid arthritis.

The numbers and sources

Effect: In 168 people with rheumatoid arthritis on standard treatment, 6 months of elk velvet antler did not differ from placebo on joint pain and swelling, disease activity, function, quality of life or CRP [4]. A systematic review identified 2 rheumatoid arthritis trials and 1 osteoarthritis trial, and its authors wrote that the osteoarthritis findings may have some promise [5].
Population: Adults with stage 2 to 3 rheumatoid arthritis [4]; RCTs [5].
Sources: [4], [5]
Caveats: One osteoarthritis trial.

Practices

Whole-body cryotherapyModerate

Ankylosing spondylitis

Shown to improve pain, function and disease activity scores in people with ankylosing spondylitis in a meta-analysis of 5 studies. C-reactive protein did not change.

The numbers and sources

Effect: Across 5 studies (310 patients), cryotherapy improved the BASDAI disease activity index (p < 0.001), ASDAS (p = 0.015), BASFI function index (p = 0.006) and pain scores (p = 0.005). C-reactive protein did not change (p = 0.684) [11].
Population: 310 people with ankylosing spondylitis in 5 studies with varied temperatures and session lengths of 80 seconds to 3 minutes [11].
Sources: [11]
Caveats: Five studies, with protocols that varied. The abstract gives p values without effect sizes, and the authors call for studies of tolerance and long-term results.

Slow breathing and breathworkLimited

Hyperventilation breathwork and inflammation

Small trials of a program combining cyclic hyperventilation, cold exposure and meditation found a blunted inflammatory response to injected endotoxin, and a fall in ESR in spondyloarthritis.

Compared with untrained volunteers [17]; a control period without training [18]

The numbers and sources

Effect: After 10 days of training in meditation, cyclic hyperventilation with breath retention, and cold immersion, 12 volunteers given intravenous endotoxin had higher plasma adrenaline and anti-inflammatory IL-10, lower TNF-alpha, IL-6 and IL-8, and fewer flu-like symptoms than 12 untrained controls [17]. In 24 patients with axial spondyloarthritis, ESR fell over 8 weeks of the program from a median of 16 to 9 mm/hr (p = 0.040) with no change in controls, and hs-CRP did not change [18]. A systematic review of 8 trials of the Wim Hof Method concluded it may reduce inflammation and found mixed effects on exercise performance [19].
Population: 24 healthy volunteers [17]. 24 patients with moderately active axial spondyloarthritis and raised hs-CRP [18]. 8 trials [19].
Sources: [17], [18], [19]
Caveats: The breathing was never tested apart from the cold and meditation in these trials. The spondyloarthritis trial was open label [18]. Endotoxin injection is a laboratory model of inflammation, not a disease [17].

Infrared saunaLimited

Rheumatoid arthritis and ankylosing spondylitis

Mixed results: pain and stiffness eased during infrared sessions in 34 patients, while changes across the 4-week course did not reach significance.

The numbers and sources

Effect: Pain and stiffness decreased significantly during a session (p < 0.05 in rheumatoid arthritis and p < 0.001 in ankylosing spondylitis). Over 4 weeks and 8 sessions, improvements in pain, stiffness and fatigue did not reach statistical significance. Disease activity scores did not change [27].
Population: 17 people with rheumatoid arthritis and 17 with ankylosing spondylitis, no control group [27].
Sources: [27]
Caveats: A pilot study with no control group.

Hyperbaric oxygen therapyModerate

Multiple sclerosis

Not shown to benefit people with multiple sclerosis in a meta-analysis of 12 randomized trials from the 1980s.

The numbers and sources

Effect: A meta-analysis of 12 randomized studies, most testing 20 sessions at 1.75 to 2.5 ATA over 4 weeks against placebo, found no clinically significant benefit and no plausible effect on the course of the disease [24].
Population: People with multiple sclerosis in 12 randomized trials run between 1983 and 1987 [24].
Sources: [24]
Caveats: No trial has compared it with current standard treatment. The reviewers leave open a small effect in an unidentified subgroup.

Whole-body cryotherapyLimited

Rheumatoid arthritis

One study found people with rheumatoid arthritis improved about equally with whole-body cryotherapy and with traditional rehabilitation over 2 weeks.

The numbers and sources

Effect: Pain, disease activity, fatigue and walking measures improved similarly in both groups, as did interleukin-6 and TNF-alpha. The Health Assessment Questionnaire result was better in the traditional rehabilitation group (p < 0.05) [19].
Population: 25 patients given cryotherapy at -110°C and 19 given traditional rehabilitation [19].
Sources: [19]
Caveats: A comparison of two active programs, not described as randomized, with no untreated group.

Diets

Carnivore dietLimited

Inflammatory bowel disease

Case reports: 10 people with ulcerative colitis or Crohn's disease, selected because they responded, reported improvement on mostly carnivore ketogenic diets.

Compared with no comparison group [4]

The numbers and sources

Effect: Six people with ulcerative colitis and four with Crohn's disease reported improvement of 72 to 165 points on the Inflammatory Bowel Disease Questionnaire [4].
Population: 10 adults with confirmed inflammatory bowel disease, recruited through a social media survey [4].
Sources: [4]
Caveats: A case series that included only people whose disease responded to the diet, so it cannot show how often it helps. No comparison group [4].

Lab markers

Thyroid peroxidase antibodies (TPO antibodies)Moderate

Later hypothyroidism

Linked to later hypothyroidism: over 20 years, women with thyroid antibodies alone had 8 times the odds, and 38 times with a raised TSH as well.

The numbers and sources

Effect: In a 20-year British follow-up, positive thyroid antibodies alone carried odds ratios for developing hypothyroidism of 8 in women (95% CI 5 to 15) and 25 in men (10 to 63). With a raised TSH as well, the odds ratios were 38 (22 to 65) and 173 (81 to 370) [7]. In an Australian cohort, hypothyroidism 13 years later was present in 12.0% of antibody-positive women whose baseline TSH was 2.5 mU/L or less, 55.2% at 2.5 to 4.0 mU/L and 85.7% above 4.0 mU/L [5]. In a 5-year Chinese survey, 14.44% of people positive for TPO or thyroglobulin antibodies developed thyroid dysfunction, against 3.31% of those without antibodies [8]. Among 82 women with subclinical hypothyroidism, overt hypothyroidism developed in 58.5% of those with microsomal antibodies and 23.2% of those without [9]. A US guideline puts progression from subclinical to overt hypothyroidism at 4.3% a year with TPO antibodies and 2.6% a year without [4].
Population: 2,779 adults in the Whickham Survey [7]. 1,184 adults in the Busselton Health Surveys [5]. 3,018 people in three Chinese regions with different iodine intakes [8]. 82 women followed a mean 9.2 years [9].
Sources: [7], [5], [8], [9], [4]
Caveats: Observational. The studies used different antibody assays and cutoffs, and earlier ones measured antibodies by semiquantitative methods, not automated immunoassay [5]. The US guideline also reports that about 75% of people with chronic autoimmune thyroiditis have raised antibody levels, many with normal thyroid function at the time [4].

Thyroid peroxidase antibodies (TPO antibodies)Limited

Thyroid inflammation after childbirth

Limited evidence: a guideline review reports postpartum thyroiditis in 33 to 50% of women who were thyroid antibody positive in the first trimester.

The numbers and sources

Effect: The American Thyroid Association reports that women who are thyroid antibody positive in the first trimester have a 33 to 50% risk of postpartum thyroiditis, and that women with the highest antibody levels have the highest risk. It reports that 10 to 20% of cases result in permanent hypothyroidism [15].
Population: A guideline summary of earlier studies, whose sizes it does not give [15].
Sources: [15]
Caveats: Secondhand figures from guideline text, not a primary study.

Thyroid peroxidase antibodies (TPO antibodies)Limited

Thyroid disease when only thyroglobulin antibodies are positive

One large US survey found thyroglobulin antibodies without TPO antibodies were not significantly associated with thyroid disease, while TPO antibodies were.

The numbers and sources

Effect: In the NHANES III survey, thyroglobulin antibodies were positive in 10.4% and TPO antibodies in 11.3% of people who reported no thyroid disease. TPO antibodies were significantly associated with hypothyroidism or hyperthyroidism and thyroglobulin antibodies were not. Thyroglobulin antibodies alone, in the absence of TPO antibodies, were not significantly associated with thyroid disease [16].
Population: 17,353 people aged 12 and older representing the US population from 1988 to 1994, of whom 16,533 reported no thyroid disease [16].
Sources: [16]
Caveats: One cross-sectional survey, using the assays of its time. Positive antibodies were more common in women, rose with age and were less common in Black participants (4.5%) than in white participants (12.3%) [16].