Fischer LM, daCosta KA, Kwock L, et al. Sex and menopausal status influence human dietary requirements for the nutrient choline. Am J Clin Nutr. 2007;85(5):1275-1285. doi:10.1093/ajcn/85.5.1275
Publication Date: "Available online 1 May 2007"
Peer Reviewed: Yes.
Study Design: "Fifty-seven adult subjects (26 men, 16 premenopausal women, 15 postmenopausal women) were fed a diet containing 550 mg choline · 70 kg−1 · d−1 for 10 d followed by <50 mg choline · 70 kg−1 · d−1 with or without a folic acid supplement (400 μg/d per randomization) for up to 42 d."
Methodology: Subjects were fed diets with controlled choline amounts; blood and urine monitored for toxicity and metabolites; liver fat assessed using MRI.
Sample Size: "57 subjects (26 men, 16 premenopausal women, and 15 postmenopausal women)"
Controls Used: "Subjects who developed organ dysfunction during this diet had normal organ function restored after incremental amounts of choline were added back to the diet."
Dose Used: "550 mg choline · 70 kg−1 · d−1" and "<50 mg choline · 70 kg−1 · d−1."
Statistical Significance Declared: "P < 0.0001," "P = 0.05," "P < 0.01," "P < 0.001," "P = 0.784; Fisher’s exact test"
Adverse Events: "No side effects were observed, other than those associated with the removal of choline… resolved when choline was added back to the diet"
Conflict of Interest: "None of the authors had a financial conflict of interest in relation to this study."

Wallace JMW, McCormack JM, McNulty H, et al. Choline supplementation and measures of choline and betaine status: a randomised, controlled trial in postmenopausal women. British Journal of Nutrition. 2012;108(7):1264-1271. doi:10.1017/S000711451100674X
Publication Date: "15 December 2011"
Peer Reviewed: Yes
Study Design: "randomised, double-blind, placebo-controlled intervention trial"
Methodology: Women aged 49-71 recruited, screened, and stratified by HRT use and fasting tHcy; received 2.4 g choline bitartrate (1 g choline) or placebo for 12 weeks; fasting blood samples collected at baseline, week 6, and week 12; plasma choline, betaine, tHcy, B-vitamins measured; compliance monitored by pill counts.
Sample Size: "forty-two healthy postmenopausal women"
Controls Used: "placebo (2·4 g tartaric acid per d)"
Dose Used: "1 g choline per d (as choline bitartrate)"
Statistical Significance Declared: "significant effects evident after 6 weeks of supplementation (P < 0·001) and remaining significant at 12 weeks (P < 0·001)"; "approached statistical significance (P = 0·058)"
Adverse Events: "no reports of side effects of supplementation"
Conflict of Interest: "No author had any conflict of interest"

DiStefano JK. The Role of Choline, Soy Isoflavones, and Probiotics as Adjuvant Treatments in the Prevention and Management of NAFLD in Postmenopausal Women. Nutrients. 2023;15(12):2670. https://doi.org/10.3390/nu15122670
Publication Date: "8 June 2023"
Peer Reviewed: Yes
Study Design: "review"
Methodology: Examination of current evidence supporting choline, soy isoflavones, and probiotics for NAFLD in postmenopausal women.
Sample Size: Not applicable (review study).
Controls Used: Not applicable (review study).
Dose Used: Not applicable (review study).
Statistical Significance Declared: Not applicable (review study).
Adverse Events: The study does not state any adverse events linked to choline supplementation. However, it does state that due to choline deficiency, "80% of postmenopausal women (12 out of 15) developed the conditions, whereas only 44% of premenopausal women (7 out of 16) did."
Conflict of Interest: "The author declares no conflict of interest."

Oyen J, Gjesdal CG, Karlsson T, Svingen GFT, Tell GS, Strand E, Drevon CA, Vinknes KJ, Meyer K, Ueland PM, Nygård O. Dietary Choline Intake Is Directly Associated with Bone Mineral Density in the Hordaland Health Study. J Nutr. 2017;147(4):572-578. doi:10.3945/jn/116.243006
Publication Date: "Available online 8 March 2017"
Peer Reviewed: Yes
Study Design: "Cross-sectional study of community-dwelling middle-aged and older adults."
Methodology: Nonfasting blood samples collected, dietary intake assessed using a validated 169-item FFQ, BMD measured by dual-energy X-ray absorptiometry, logistic regression, and Spearman's bivariate rank order correlation used for analysis.
Sample Size: "2649 women and 1983 men (aged 46–49 or 71–74 y)."
Controls Used: Adjusted for BMI, plasma cotinine (nicotine exposure), hs-CRP, energy-adjusted dietary vitamin D, calcium, physical activity, age group, and sex.
Dose Used: "Median energy-adjusted total choline intakes in middle-aged women and men were 255 mg/d (IQR: 63 mg/d) and 259 mg/d (IQR: 74 mg/d), respectively, and in elderly women and men 265 mg/d (IQR: 61 mg/d) and 258 mg/d (IQR: 61 mg/d), respectively."
Statistical Significance Declared: "OR: 1.83; 95% CI: 1.24, 2.69; P = 0.002" for free choline in middle-aged men. "OR: 2.13; 95% CI: 1.43, 3.16; P < 0.001" for glycerophosphocholine in middle-aged men. "OR: 1.96; 95% CI: 1.33, 2.88; P = 0.001" for total choline in elderly women. "OR: 1.94; 95% CI: 1.33, 2.84: P = 0.001" for phosphatidylcholine in elderly women.
Adverse Events due to Choline Supplementation: The study does not declare any adverse events directly linked to choline supplementation.
Conflict of Interest: "No conflicts of interest."

Zeisel SH. Choline: an essential nutrient for humans. Nutrition. 2000;16(7):669-671. doi:10.1016/S0899-9007(00)00349-X
Publication Date: Available online 20 July 2000.
Peer Reviewed: Yes.
Study Design: Comprehensive review.
Methodology: Review of existing studies on choline's role in human and animal health, including its synthesis, metabolism, and effects of deficiency.
Sample Size: Various sample sizes in cited studies; specific numbers not provided in the review.
Controls Used: Not applicable (review study).
Dose Used: Not applicable (review study).
Statistical Significance Declared: Not applicable (review study).
Adverse Events due to Choline Supplementation: No direct adverse events linked to choline supplementation stated in the review.
Conflict of Interest: "This study was supported by the National Institutes of Health (AG09525 and DK). Support for this work was also provided by grants from the NIH to the UNC Clinical Nutrition Research Unit (DK56350)."

Wallace TC, Blusztajn JK, Caudill MA, Klatt KC, Zeisel SH. Choline: The Neurocognitive Essential Nutrient of Interest to Obstetricians and Gynecologists. J Dietary Suppl. 2020;17(6):733-752. doi:10.1080/19390211.2019.1639875
Publication Date: "2020"
Peer Reviewed: Yes
Study Design: "randomized controlled trial"
Methodology: Randomized controlled trials, observational studies, feeding trials in humans and animals.
Sample Size: "n = 24", "100 women", "several preclinical investigations", "7 patients with Alzheimer’s disease"
Controls Used: "placebo-treated", "fruit control"
Dose Used: "480 or 930 mg/day" in human maternal supplementation; "7.5 g/d" and "8–20 g/d" in toxicity studies.
Statistical Significance Declared: "higher circulating and urinary concentrations of TMAO (42–62 times; p < 0.0001)"
Adverse Events due to Choline Supplementation: No direct adverse events linked to typical supplementation doses in general population studies, "High intakes of choline are associated with a fishy body odor, vomiting, excessive sweating and salivation, hypotension, and liver toxicity." (>7.5 g/d)
Conflict of Interest: "TCW, JKB, MAC, and SHZ disclose research grant funding, scientific consulting or writing fees, travel reimbursement, and speaker honoraria from various food companies and commodity boards with an interest in choline. KCK is a graduate research assistant to MAC and has no direct conflict of interest to disclose."

Zhang CX, Pan MX, Li B, Wang L, Mo XF, Chen YM, Lin FY, Ho SC. Choline and betaine intake is inversely associated with breast cancer risk: A two-stage case-control study in China. Cancer Sci. 2012 Nov 12. doi:10.1111/cas.12064
Publication Date: "First published: 12 November 2012"
Peer Reviewed: Yes
Study Design: "two-stage case-control study"
Methodology: A validated food frequency questionnaire was used to assess dietary intake by face-to-face interview. Unconditional logistic regression models were used to estimate odds ratios and confidence intervals, adjusting for potential confounding variables including occupation, BMI, age at menarche, live births, family history of breast cancer, passive smoking, alcohol consumption, physical activity, and total energy intake.
Sample Size: "807 cases and 807 age- (5-year interval) and residence (rural/urban)-matched controls"
Controls Used: "Control subjects were patients with no history of cancer who were admitted to the same hospitals during the same time period as the case subjects."
Dose Used: "The mean dietary choline intake in the control group of the present study was 173 mg/day."
Statistical Significance Declared: "Adjusted OR for the highest quartile of intake compared with the lowest were 0.40 (95% CI = 0.28–0.57, Ptrend < 0.001) for total choline intake, 0.58 (95% CI = 0.42–0.80, Ptrend < 0.001) for betaine intake and 0.38 (0.27–0.53, Ptrend < 0.001) for choline plus betaine intake."
Adverse Events due to Choline Supplementation: None reported.
Conflict of Interest: "The authors have no conflict of interest."

Yu D, Shu XO, Xiang YB, Li H, Yang G, Gao YT, Zheng W, Zhang X. Higher Dietary Choline Intake Is Associated with Lower Risk of Nonalcoholic Fatty Liver in Normal-Weight Chinese Women. J Nutr. 2014;144(12):2034-2040. doi:10.3945/jn.114.197533
Publication Date: "Available online 15 October 2014"
Peer Reviewed: Yes.
Study Design: "population-based prospective cohort studies."
Methodology: Face-to-face interviews with validated food-frequency questionnaires, in-person baseline surveys, home visits every 2-3 years, annual records linkage, ultrasound examinations, multivariate logistic regression.
Sample Size: "The final analysis included 37,432 women and 18,763 men."
Controls Used: "Participants with existing hepatitis, cardiovascular disease, or cancer, extreme energy intakes, heavy alcohol consumption, and diagnosis of fatty liver at or before baseline were excluded."
Dose Used: "Mean ± SD intakes of total choline were 289 ± 85 mg/d in women and 318 ± 92 mg/d in men."
Statistical Significance Declared: "The ORs (95% CIs) for the highest vs. the lowest quintiles of choline intake were 0.68 (0.59, 0.79) in women and 0.75 (0.60, 0.93) in men (both P-trend < 0.01)."
Adverse Events due to Choline Supplementation: No adverse events linked to choline supplementation were declared.
Conflict of Interest: "All authors contributed to the preparation of the manuscript and read and approved the final manuscript."