Table 1.
Highest level of evidence in human studies of lifestyle modification on glioblastoma survival.
| Category | Type of Study | Author | Findings | Current Clinical Trial | Current Status; Estimated Date of Completion |
|---|---|---|---|---|---|
| Ketogenic Diet | Prospective randomized clinical trial | Voss et al. [28] | Patients in the ketogenic diet–intermittent fasting group receiving reirradiation for GBM who achieved blood glucose levels < 83.5 mg/dL had significantly longer PFS and OS | Ketogenic diet in combination with standard-of-care radiation and temozolomide for patients with glioblastoma (NCT03451799) | Recruiting; April 2021 |
| Feasibility study of modified Atkins ketogenic diet in the treatment of newly diagnosed malignant glioma (NCT03278249) | Recruiting; January 2021 |
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| Feasibility, safety, and efficacy of a metabolic therapy program in conjunction with standard treatment for glioblastoma multiforme (NCT04730869) | Not yet recruiting; November 2022 |
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| Calorie Restriction | No human trials; mouse studies only | N/A | N/A | Glioma modified Atkins-based diet in patients with glioblastoma (GLAD) (NCT02286167) | Completed with no results posted yet; July 2019 |
| Characterization of metabolic changes in the glioma tumor tissue induced by transient fasting (ERGO3) (NCT04461938) | Recruiting; March 2022 |
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| Exercise | Prospective observational cohort study | Ruden et al. [41] | Exercise behavior is an independent predictor of survival with those exercising ≥ 9 MET-h/wk having a median survival of 21.84 months compared to 13.03 months in those exercising < 9 MET-h/wk | Does exercise improve progression-free survival in glioblastoma? A prospective single arm intervention trial (NCT03390569) | Recruiting; December 2020 |
| Influence of physical activity in patients with high grade glioma on patients’ psychological well being, sleep and quality of life (NCT03775369) | Recruiting; December 2021 |
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| Vitamin A | Multi-center phase II clinical trial | Jaeckle et al. [49] | Patients with recurrent glioblastoma receiving cis-retinoid acid and temozolomide exceeded the goal of 20% increase in PFS at 6 months compared to historical controls | Phase I/II adaptive randomized trial of vorinostat, isotretinoin, and temozolomide in adults with recurrent glioblastoma multiforme (NCT00555399) | Active, not recruiting; November 2024 |
| Vitamin B3 | No human studies | N/A | N/A | A phase I/II study of niacin in patients with newly diagnosed glioblastoma receiving concurrent radiotherapy and temozolomide followed by monthly temozolomide (NCT04677049) | Recruiting; January 2026 |
| Vitamin C | Phase 1 clinical trial | Schoenfeld et al. [57] | High-dose ascorbic acid is safe and well-tolerated in patients with glioblastoma with a trend toward longer PFS and overall survival compared to historical averages | Pharmacological ascorbate combined with radiation and temozolomide in glioblastoma multiforme: A Phase 2 trial (NCT02344355) | Active, not recruiting; December 2024 |
| A phase I trial of high-dose ascorbate in glioblastoma multiforme (NCT01752491) | Active, not recruiting; December 2021 |
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| Vitamin D | Phase 2 clinical trial | Trouillas et al. [68] | Oral alfacalcidol is safe. 20% of glioblastoma patients had significant clinical and radiographic response and were alive >4 years after diagnosis | None | N/A |
| Melatonin | Randomized controlled trial | Lissoni et al. [78] | 42.9% of glioblastoma patients receiving oral melatonin in addition to radiotherapy were alive at one year compared to 6.2% of those receiving radiotherapy alone | None | N/A |
| Caffeine | Phase 2 clinical trial | Stewart et al. [98] | Caffeine-induced seizures prevented dose escalation to a therapeutic level | None | N/A |
| Alcohol | No human studies | N/A | N/A | None | N/A |
| Cannabis | Randomized double-blind placebo-controlled trial | Twelves et al. [114] | 1-year survival in patients receiving CBD:THC with temozolomide was 83% compared to 56% in those receiving temozolomide plus placebo | Phase Ib, open-label, multicenter, intrapatient dose-escalation clinical trial to assess the safety profile of the TN-TC11G (THC + CBD) combination with temozolomide and radiotherapy in patients with newly diagnosed glioblastoma (NCT03529448) | Not yet recruiting; June 2023 |
| Smoking Cessation | Retrospective cohort study | Paravati et al. [120] | Smokers with KPS < 70 have median survival of 5.2 months compared to 8 months in nonsmokers with KPS < 70 | None | N/A |
| Marital Status | Retrospective population-based cohort study | Xie et al. [123] | Longer overall survival for married patients | None | N/A |
Abbreviation: Karnofsky performance scale (KPS); progression-free survival (PFS); metabolic-equivalent hours per week (MET-h/wk).