# Interpretable Prediction of Late‐Stage CKM Syndrome Association From Dietary Nutrients in Accelerated Aging Using SHAP and LIME

**Authors:** Hongxiang Tu, Meijie Dai, Yanying Zhu, Min Liang, Mo Shen, Yuehui Chen

PMC · DOI: 10.1002/fsn3.71547 · Food Science & Nutrition · 2026-02-17

## TL;DR

This study explores how dietary nutrients affect the risk of late-stage cardiovascular-kidney-metabolic syndrome in people with accelerated aging, using machine learning and interpretability tools.

## Contribution

The novel use of SHAP and LIME to interpret machine learning models for predicting CKM syndrome progression based on dietary nutrients in accelerated aging populations.

## Key findings

- Dietary nutrient mixtures are inversely associated with late-stage CKM syndrome risk in individuals with accelerated aging.
- LightGBM and Random Forest models showed the highest predictive accuracy for CKM progression.
- Selenium, sodium, and moisture were identified as prominent protective contributors to reducing CKM risk.

## Abstract

The association between habitual dietary nutrient intake and the risk of late‐stage progression of cardiovascular–kidney–metabolic (CKM) syndrome among individuals with accelerated aging remains insufficiently understood. Data were obtained from seven cycles (2005–2018) of the U.S. National Health and Nutrition Examination Survey (NHANES). Six machine learning models were developed to predict late‐stage CKM progression. SHapley Additive exPlanations (SHAP) and Local Interpretable Model‐Agnostic Explanations (LIME) were applied to quantify the relative contributions of individual dietary nutrients to disease risk. Among the evaluated machine learning models, LightGBM and Random Forest demonstrated the highest predictive performance. Time‐series validation further indicated stable model performance across survey cycles. SHAP analysis showed that, when demographic characteristics and dietary intake were jointly incorporated, the strongest negative contributors to late‐stage CKM risk were vitamin B12 (0.011), selenium (0.009), sodium (0.008), moisture (0.008), vitamin B6 (0.008), and vitamin E (0.007). When analyses were restricted to dietary nutrients alone, the leading negative contributors were moisture (0.0597), sodium (0.0368), caffeine (0.0251), niacin (0.0192), vitamin D (0.0191), selenium (0.0188), vitamin B12 (0.0177), and lutein + zeaxanthin (0.0166). Dietary nutrient mixtures are inversely associated with the risk of late‐stage CKM progression in individuals with accelerated aging. LightGBM and Random Forest models achieved superior predictive accuracy. Selenium, sodium, and moisture emerged as prominent protective contributors.

Dietary nutrient mixtures are inversely associated with the risk of late‐stage CKM progression in individuals with accelerated aging. LightGBM and Random Forest demonstrated the highest predictive accuracy. Selenium, sodium, and moisture were among the most notable protective contributors.

## Linked entities

- **Chemicals:** selenium (PubChem CID 6326970), sodium (PubChem CID 5360545), vitamin B12 (PubChem CID 73415824), vitamin B6 (PubChem CID 1054), vitamin E (PubChem CID 14985), caffeine (PubChem CID 2519), niacin (PubChem CID 938), lutein + zeaxanthin (PubChem CID 9876812)

## Full-text entities

- **Genes:** CKM (creatine kinase, M-type) [NCBI Gene 1158] {aka CKMM, CPK-M, M-CK}, SHROOM4 (shroom family member 4) [NCBI Gene 57477] {aka MRXSSDS, SHAP, shrm4}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, LIME1 (Lck interacting transmembrane adaptor 1) [NCBI Gene 54923] {aka LIME, dJ583P15.4}
- **Diseases:** chronic diseases (MESH:D002908), Metabolic dysregulation (MESH:D021081), metabolic abnormalities (MESH:D008659), Vitamin D deficiency (MESH:D014808), CKM Syndrome (MESH:D007674), obesity (MESH:D009765), type 2 diabetes (MESH:D003924), CKD (MESH:D051436), NCHS (OMIM:603663), dehydration (MESH:D003681), prediabetes (MESH:D011236), CVD (MESH:D002318), coronary heart disease (MESH:D003327), hypertension (MESH:D006973), cardiovascular and metabolic disorders (MESH:D024821), Inflammation (MESH:D007249)
- **Chemicals:** folate (MESH:D005492), beta-cryptoxanthin (MESH:D000072743), calcium (MESH:D002118), creatinine (MESH:D003404), glucose (MESH:D005947), magnesium (MESH:D008274), cholesterol (MESH:D002784), vitamin C (MESH:D001205), copper (MESH:D003300), alcohol (MESH:D000438), vitamin B6 (MESH:D025101), vitamin B12 (MESH:D014805), alpha-tocopherol (MESH:D024502), retinol (MESH:D014801), beta-carotene (MESH:D019207), iron (MESH:D007501), lipid (MESH:D008055), vitamin B3 (MESH:D009536), carotenoids (MESH:D002338), lycopene (MESH:D000077276), polyphenols (MESH:D059808), monounsaturated fatty acids (MESH:D005229), carbohydrate (MESH:D002241), fatty acids (MESH:D005227), Lutein (MESH:D014975), theobromine (MESH:D013805), Selenium (MESH:D012643), triglycerides (MESH:D014280), vitamin B2 (MESH:D012256), choline (MESH:D002794), vitamin B1 (MESH:D013831), homocysteine (MESH:D006710), Vitamin E (MESH:D014810), vitamin K (MESH:D014812), Niacin (MESH:D009525), omega-3 fatty acids (MESH:D015525), Caffeine (MESH:D002110), sodium (MESH:D012964), zinc (MESH:D015032), sugar (MESH:D000073893), zeaxanthin (MESH:D065146), polyunsaturated fatty acids (MESH:D005231), phosphorus (MESH:D010758), potassium (MESH:D011188), vitamin D (MESH:D014807), DCA (-), alpha-carotene (MESH:C041635)
- **Species:** Homo sapiens (human, species) [taxon 9606]

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## References

45 references — full list in the complete paper: https://tomesphere.com/paper/PMC12913708/full.md

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Source: https://tomesphere.com/paper/PMC12913708