Clinician Q&A: Understanding the Complex Relationship Between Alcohol Use and RA

There is ongoing debate regarding the effects of alcohol intake on health, with many studies linking light to moderate consumption with a reduced risk for cardiovascular disease, ischemic stroke, and diabetes. However, other studies have concluded that there is no safe level of alcohol intake owing to its adverse effects on health and mortality.^1-3 In the field of rheumatology, findings from various studies have suggested the protective effects of alcohol on rheumatoid arthritis (RA), though results in this area are largely inconclusive.

“Low to moderate alcohol consumption is inversely associated with the development of RA in a manner that appears to be dose-dependent, time-dependent, and sex-dependent,” noted Rajat Bhatt, MD, a rheumatologist at Prime Rheumatology in Richmond, Texas. “However, there are several confounding factors, including better self-reported scores by patients using alcohol.”

The Inverse Association: Alcohol Intake Levels and RA

In a systematic review and meta-analysis published in 2021 in Scientific Reports, study authors examined 14 observational studies exploring the effects of alcohol consumption on disease activity and outcomes in a total of 16,347 patients with RA.⁴

The results showed pooled mean differences in disease activity scores (DAS28) of 0.34 (95% CI, 0.24-0.44; P <10⁻⁵) between drinkers and nondrinkers, with lower scores in nondrinkers; 0.33 (95% CI, 0.05-0.62; P =.02) between heavy drinkers and nondrinkers, with lower scores in heavy drinkers; and 0.00 (95% CI, -0.30 to 0.30; P =.98) between low-risk and high-risk drinkers.⁴

In addition, health assessment questionnaire (HAQ) scores were significantly different in drinkers compared with nondrinkers, with lower HAQ scores reported by drinkers (0.3; 95% CI, 0.18-0.41; P <10⁻⁵).⁴

These results align with those of other research indicating the protective effects of alcohol intake on RA risk. A prospective cohort study conducted in 2021 also linked alcohol consumption to a 30% reduction in RA incidence (hazard ratio [HR], 0.69; 95% CI, 0.55-0.86).⁵

“The contribution of alcohol to the pathogenesis of RA remains poorly understood,” said Matthew A. Turk, MSc, a medical student in the department of rheumatology at the University College Dublin in Ireland and coauthor of the Scientific Reports paper.⁴ “Broadly speaking, the general immunosuppressive effects of alcohol may lower systemic immune activation.” 

This potential pathway is also supported by research suggesting protective effects of low to moderate alcohol use in other autoimmune diseases including systemic lupus erythematosus, multiple sclerosis, autoimmune thyroid disease, and autoimmune diabetes. These effects may be partially mediated by the gut microbiome.⁶

Nonetheless, findings on the effects of alcohol intake in RA remain mixed. A study published in 2020 in Arthritis Care and Research reported “no clear benefit of alcohol consumption in RA” and found that higher “disease activity, disability, comorbidity, and poor quality of life contribute to reductions in alcohol use.” Thus, the inverse relationship observed between alcohol intake and disease activity in RA may be explained by reverse causality, authors of the study wrote.⁷

A prospective cohort study published in 2021 in Nutrients demonstrated the harmful impact of increased alcohol use on RA risk, and this association appeared to vary by sex. Each 10 g increase in alcohol intake was significantly associated with an increased risk for RA in women (HR, 1.56; 95% CI, 1.06-2.29), but not in men (HR, 1.10; 95% CI, 0.97-1.25), highlighting the importance of examining sex differences in future research in this area.⁸

Clinical Implications and Research Gaps

“I think the small correlation between moderate alcohol consumption and slightly lower average disease activity should be taken with caution, and we should encourage our patients to live a healthy, active lifestyle that includes being mindful of alcohol use,” Turk advised. “We can reassure them that they may be able to enjoy a drink from time to time, but we should not be encouraging marked increases in alcohol consumption.”

Dr Bhatt agreed and added that patients receiving RA medications, such as methotrexate and leflunomide, should be encouraged to reduce or cease alcohol consumption as it interferes with liver function and increases medication side effects. In general, an emphasis on healthy lifestyles is needed, including “meditation, stress management, sleep, and a sea change in thinking about disease management,” he said.

In terms of research gaps regarding this topic, “[Randomized controlled trials] would be a good next step to investigate whether a true therapeutic relationship exists between moderate alcohol consumption and decreased overall disease activity in RA,” Turk stated. “We are also lacking data in the basic sciences as to how alcohol is immunosuppressive, specifically in RA.”

To get further insight into the alcohol-RA connection, we interviewed Leanna M. Wise, MD, rheumatologist and assistant professor of clinical medicine in the Division of Rheumatology at Keck Medicine of the University of Southern California in Los Angeles.

What does current literature indicate about the association between alcohol intake and RA and how can these studies be interpreted? 

Dr Wise: As with nearly all studies relating to nutrition and dietary intake, it is difficult to parse out direct effects of certain foods or beverages on chronic diseases due to the presence of many confounders, including concomitant intake of health-promoting or disease-promoting foods, exercise, tobacco use, and weight. The nature of self-reported survey data and the need for high-quality longitudinal studies also complicates studies on nutritional patterns and their relationship with chronic disease development and prognosis.

Nevertheless, large epidemiologic cohort studies such as the Nurse’s Health Study I and II, and a large cohort study from Sweden suggest that moderate consumption of alcohol may actually be protective against development of RA.^9,10 Smaller studies also suggest that alcohol consumption may be associated with less severe RA and progression, as well as a decrease in mortality.^11,4

It is important to also know that the vast majority of participants in the aforementioned cohorts were [White], so it is crucial to explore this potential association in non-[White] groups as well. There is also a question about whether the protective effect may be limited to RA profiles with anticitrullinated peptide positivity.¹²

What are some of the proposed mechanisms underlying the link between alcohol consumption and RA?

Dr Wise: Both beer and wine have high concentrations of polyphenols, which are naturally occurring anti-inflammatory agents that appear to have a variety of beneficial roles in immune modulation and reducing pro-inflammatory and pro-autoimmune states.^13,14 Polyphenol intake has also been linked to a beneficial effect on mitigating cardiovascular disease and obesity, both of which occur at high rates in patients with RA.^15,16 The direct effect of alcohol may also interact with the immune system in a regulatory manner.¹⁷

Based on available data, and in light of the potential inverse relationship between alcohol and RA, can you offer guidance to rheumatology providers on counseling patients about alcohol intake?

Dr Wise: While data appear to be in favor of some alcohol consumption being beneficial in RA development and symptomatology, providers should be sure to counsel their patients that this in no way gives them a carte blanche for excessive alcohol use, given the risk for substance abuse or dependency, as well as the increased risk for certain cancers and liver disease with frequent excessive alcohol consumption.

Providers should address alcohol use in patients with RA and caution them to not consume more than the recommended daily amount – no more than 2 daily drinks for men and no more than 1 daily drink for women.¹⁸

Importantly, the potentially increased risk for hepatotoxicity with RA medications and alcohol use needs to be weighed for each patient.

Finally, given that the benefits of alcohol consumption may stem largely from the concurrent consumption of polyphenols in beer and wine, patients should be encouraged to follow a diet high in polyphenol-containing foods, such as fruits and vegetables, rather than rely on alcohol use alone to obtain these beneficial compounds.

What kind of interventions need to be conducted next to further explore and understand the link between alcohol use and RA?

Dr Wise: Some big-picture concepts to be considered are whether patients who have more mild disease tend to feel better and thus are more liberal with their alcohol use, and whether patients who have worse disease have the potential to self-medicate with alcohol use.⁷ A burgeoning field in immunology is focused on the effects of polyphenols on the gut microbiota and the downstream effects on systemic immune function.⁶ The role of alcohol – and its specific polyphenolic constituents – should be explored in this setting.

References

1.     Chiva-Blanch G, Badimon L. Benefits and risks of moderate alcohol consumption on cardiovascular disease: current findings and controversies. Nutrients. 2019;12(1):108. doi:10.3390/nu12010108

2.     Mayo Clinic. Alcohol use: Weighing risks and benefits. Accessed January 11, 2022. https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/in-depth/alcohol/art-20044551

3.     GBD 2016 Alcohol Collaborators. Alcohol use and burden for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2018;392(10152):1015-1035. doi:10.1016/S0140-6736(18)31310-2

4.     Turk JN, Zahavi ER, Gorman AE, Murray K, Turk MA, Veale DJ. Exploring the effect of alcohol on disease activity and outcomes in rheumatoid arthritis through systematic review and meta-analysis. Sci Rep. 2021;11(1):10474. doi:10.1038/s41598-021-89618-1

5.     Hedenstierna L, Bellocco R, Ye W, et al. Effects of alcohol consumption and smoking on risk for RA: results from a Swedish prospective cohort study. RMD Open. 2021;7(1):e001379. doi:10.1136/rmdopen-2020-001379

6.     Caslin B, Mohler K, Thiagarajan S, Melamed E. Alcohol as friend or foe in autoimmune diseases: a role for gut microbiome? Gut Microbes. 2021;13(1):1916278. doi:10.1080/19490976.2021.1916278

7.     Baker JF, England BR, Mikuls TR, et al. Changes in alcohol use and associations with disease activity, health status, and mortality in rheumatoid arthritis. Arthritis Care Res (Hoboken). 2020;72(3):301-308. doi:10.1002/acr.23847

8.     VanEvery H, Yang W, Olsen N, et al. Alcohol consumption and risk of rheumatoid arthritis among Chinese Adults: a prospective study. Nutrients. 2021;13(7):2231. doi:10.3390/nu13072231

9. Di Giuseppe D, Alfredsson L, Bottai M, Askling J, Wolk A. Long term alcohol intake and risk of rheumatoid arthritis in women: a population based cohort study. BMJ. 2012;345:e4230. doi:10.1136/bmj.e4230

10.  Lu B, Solomon DH, Costenbader KH, Karlson EW. Alcohol consumption and risk of incident rheumatoid arthritis in women: a prospective study. Arthritis Rheumatol. 2014;66(8):1998-2005. doi:10.1136/bmj.e4230

11.  Maxwell JR, Gowers IR, Moore DJ, Wilson AG. Alcohol consumption is inversely associated with risk and severity of rheumatoid arthritis. Rheumatology (Oxford). 2010;49(11):2140-2146. doi:10.1093/rheumatology/keq202

12.  Scott IC, Tan R, Stahl D, Steer S, Lewis CM, Cope AP. The protective effect of alcohol on developing rheumatoid arthritis: a systematic review and meta-analysis. Rheumatology (Oxford). 2013;52(5):856-867. doi:10.1093/rheumatology/kes376

13.  Osorio-Paz I, Brunauer R, Alavez S. Beer and its non-alcoholic compounds in health and disease. Crit Rev Food Sci Nutr. 2020;60(20):3492-3505. doi:10.1080/10408398.2019.1696278

14.  Ding S, Jiang H, Fang J. Regulation of immune function by polyphenols. J Immunol Res. 2018;2018:1264074. doi:10.1155/2018/1264074

15.  Stefania S, Clodoveo ML, Cariello M, et al. Polyphenols and obesity prevention: critical insights on molecular regulation, bioavailability and dose in preclinical and clinical settings. Crit Rev Food Sci Nutr. 2021;61(11):1804-1826. doi:10.1080/10408398.2020.1765736

16.  Tangney CC, Rasmussen HE. Polyphenols, inflammation, and cardiovascular disease. Curr Atheroscler Rep. 2013;15(5):324. doi:10.1007/s11883-013-0324-x

17.  Azizov V, Dietel K, Steffen F, et al. Ethanol consumption inhibits T_FH cell responses and the development of autoimmune arthritis. Nat Commun. 2020;11(1):1998. doi:10.1038/s41467-020-15855-z

18.  US Department of Agriculture and US Department of Health and Human Services. Dietary guidelines for Americans, 2020-2025. 9th Edition. Published December 2020. Accessed January 11, 2022. https://www.dietaryguidelines.gov/sites/default/files/2020-12/Dietary_Guidelines_for_Americans_2020-2025.pdf