Reducing saturated fat intake shows mortality benefit, but only in high-risk individuals

Embargoed for release until 5:00 p.m. ET on Monday 15 December 2025   

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Below please find summaries of new articles that will be published in the next issue of Annals of Internal Medicine. The summaries are not intended to substitute for the full articles as a source of information. This information is under strict embargo and by taking it into possession, media representatives are committing to the terms of the embargo not only on their own behalf, but also on behalf of the organization they represent.   
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1. Reducing saturated fat intake shows mortality benefit, but only in high-risk individuals

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-25-02229

Editorial: https://www.acpjournals.org/doi/10.7326/ANNALS-25-04971

URL goes live when the embargo lifts             

A systematic review of 17 randomized trials found that among high cardiovascular risk individuals, reducing saturated fat was linked to lower all-cause mortality and possible reductions in cardiovascular deaths, heart attacks, and strokes. Notably, the greatest benefit for preventing nonfatal heart attacks occurred when saturated fats were replaced with polyunsaturated fats (PUFA) rather than simply reducing them. For people at low to intermediate cardiovascular risk, cutting or replacing saturated fat intake offered little or no benefit over 5 years. The study is published in Annals of Internal Medicine.  

Researchers from the University of Toronto, McMaster University, Texas A&M University, and colleagues reviewed trials involving 66,337 participants that compared the effect of reducing saturated fat intake or replacement with alternative nutrients such as PUFA on mortality and cardiovascular-related outcomes over at least two years. The data showed that overall, reducing saturated fat intake resulted in important reductions in total cholesterol and low-density lipoprotein cholesterol (LDL-C). For high-risk individuals, low to moderate certainty evidence showed that reducing saturated fat intake may have important benefits for all-cause mortality, cardiovascular mortality, nonfatal myocardial infarction (MI), and stroke. In particular, replacing saturated fat with PUFA showed important absolute reductions in nonfatal MI risk. For low-risk individuals, absolute benefits were not important. These findings suggest that saturated fat reduction may be most relevant for high-risk populations, and that PUFA replacement could enhance benefits. 

Media contacts: For an embargoed PDF, please contact Gabby Macrina at gmacrina@acponline.org. To contact corresponding author Bradley C. Johnston, PhD, please email bradley.johnston@tamu.edu.  

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2.  Screening based on smoking duration may reduce racial disparities in lung cancer detection

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-25-00464

URL goes live when the embargo lifts             

A large, prospective, and racially diverse study evaluating the effect of alternative eligibility criteria for lung cancer screening found that using smoking duration rather than pack-years reduced screening eligibility gaps among African Americans and Latinos relative to Whites. This screening approach also improved 6-year lung cancer detection sensitivity across all races. The study is published in Annals of Internal Medicine.

In 2021, the United States Preventive Services Task Force (USPSTF) lowered lung cancer screening thresholds to 20 pack-years and age 50 to broaden screening eligibility and reduce racial disparities, but gaps remain because pack-years emphasize smoking intensity over duration. Risk-based screening, already adopted internationally, has shown superior detection and reduced disparities, yet its performance compared to duration-based criteria in diverse U.S. populations has not been fully evaluated.

Researchers from Stanford University School of Medicine and colleagues analyzed data for 105,261 adults aged 45–75 years with a smoking history in California and Hawaii who were enrolled in the Multiethnic Cohort Study from 1993 to 1996 to evaluate screening eligibility and prognostic performance of alternative smoking-duration-based criteria vs USPSTF-2021 (≥20 pack-years) and risk-based screening using the recalibrated PLCOm2012_update (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial 2012) model. They found that under USPSTF-2021 criteria, 24% of participants were eligible for screening, with lower rates among African Americans and Latinos compared with Whites. Duration-based criteria increased eligibility for African Americans and Latinos while maintaining similar overall eligibility. Detection sensitivity improved under duration-based criteria, though specificity decreased slightly. Risk-based screening achieved the highest overall sensitivity and specificity but widened eligibility gaps between Latinos and Whites and showed lower sensitivity for Latinos. These findings suggest that smoking duration–based criteria may offer a viable alternative to pack-year based screening, while risk-based approaches may require refinement to ensure equity.

Media contacts: For an embargoed PDF, please contact Gabby Macrina at gmacrina@acponline.org. To contact corresponding author Summer S. Han, PhD please email summer.han@stanford.edu. 

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3. Diagnostic follow-up after positive lung cancer screening often falls short of guidelines

Only 60% of patients receive guideline concordant follow-up after positive lung cancer screening

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-25-00772

URL goes live when the embargo lifts             

A retrospective cohort study assessed diagnostic follow-up after positive low-dose computed tomography (LDCT) lung cancer screening results among Medicare beneficiaries. Researchers found that only about 60% of patients received guideline-concordant care, while nearly one-third had less intensive follow-up than recommended. Non-Hispanic Black, Asian, and Hispanic patients, current smokers, and those undergoing baseline screening were more likely to receive less intensive care. The study is published in Annals of Internal Medicine. 

Researchers from the National Cancer Institute and colleagues analyzed linked data from the American College of Radiology Lung Cancer Screening Registry and Medicare claims for 64,555 adults aged 65 years or older with a first positive LDCT screening result between 2015 and 2021. Positive results were categorized using Lung-RADS scores (3, 4A, 4B, 4X). Overall, 59.7% of participants received guideline-concordant follow-up, 32.3% received less intensive care, and 7.9% received more intensive care. Concordance increased with higher Lung-RADS scores. Within one year, 12.4% of participants were diagnosed with lung cancer, with rates rising alongside follow-up intensity. Invasive procedures were performed in 16.2% of participants overall and in 7.3% of those without lung cancer, including 0.8% who underwent lung resection. These findings highlight gaps in adherence to follow-up guidelines and persistent racial disparities, suggesting a need for targeted interventions to improve timely and appropriate care and improve lung cancer screening outcomes.

Media contacts: For an embargoed PDF, please contact Gabby Macrina at gmacrina@acponline.org. To contact corresponding author Paul F. Pinsky, PhD please email Kara Smigel smigelk@mail.nih.gov.

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4. Bisphosphonates may reduce short-term pain in complex regional pain syndrome but increase adverse events

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-25-03693

URL goes live when the embargo lifts             

A systematic review and meta-analysis has found that bisphosphonates - medicines commonly used to treat osteoporosis - may offer short-term pain relief for people with complex regional pain syndrome (CRPS), but the benefits are uncertain beyond the short term and side effects are likely. The study, the largest analysis of a CRPS treatment to date, is published in Annals of Internal Medicine.

CRPS is a severe and often disabling chronic pain condition that usually develops in a limb after injury or surgery and. Effective treatments are extremely limited, and many patients experience persistent pain, disability and reductions in quality of life.

Researchers from the University of New South Wales Sydney, Neuroscience Research Australia, Brunel University London, University of Liverpool, and colleagues analyzed 11 randomized controlled trials (RCTs) involving 754 adults with CRPS to determine the benefits and harms of bisphosphonates for CRPS. The included evidence evaluated 5 bisphosphonate types given orally or by intravenous infusion. The review found that bisphosphonates may reduce pain intensity in the short-term (around 1 to 3 months after treatment), but immediate- medium- and long-term effects were unclear. The data suggest that bisphosphonates probably increase the risk for adverse events, including joint and muscle, though serious harms were rare. The researchers noted considerable variability in results across studies that could not be fully explained. Some findings hinted that patients with greater underlying bone metabolism changes - one theorized driver of CRPS in its early stages - may respond more favorably, but current evidence is insufficient to confirm this. Overall, the authors say that while bisphosphonates may offer short-term pain relief for CRPS, clinicians should weigh potential benefits against adverse effects and the lack of long-term efficacy data. They add that more research is needed to identify who is most likely to benefit and to determine optimal dosing and treatment duration.

Media contacts: For an embargoed PDF, please contact Gabby Macrina at gmacrina@acponline.org. To contact corresponding author Michael C. Ferraro, BSc (Hons) [m.ferraro@unsw.edu.au] please email Kate Burke at kate.burke@unsw.edu.au. 

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