Higher dietary intakes of choline and betaine are associated with a lower risk of liver cancer

The dietary intake of methyl donors is favorably associated with many diseases, but the findings regarding primary liver cancer (PLC) risk are limited. This study investigated the association between the intake of choline, betaine and methionine and PLC risk in adults. This 1:1 matched case-control study enrolled 644 hospital-based PLC patients and 644 community-based controls who were matched by sex and age, in Guangzhou, China. An interviewer-administered questionnaire and a food-frequency questionnaire were used to collect general information and dietary intake information. Conditional logistic regression showed a significantly inverse association between total choline and betaine intakes and PLC risk. The multivariable-adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) for PLC for the top (vs. bottom) tertile were 0.34 (0.24-0.49; P -trend < 0.001) for total choline and 0.67 (0.48-0.93; P -trend = 0.011) for betaine. No significant association was observed between the intake of methionine and PLC risk (P > 0.05). For individual choline compounds, higher consumptions of free choline, glycerophosphocholine, phosphocholine, phosphatidylcholine and sphingomyelin were associated with a lower PLC risk (all P-trend < 0.05). The studied associations were not significantly modified by the folate intake (P-interactions: 0.488-0.890). Our findings suggest that higher choline and betaine intakes may be associated with a lower risk of PLC.

Zhou, R. F., et al. (2017). "Higher dietary intakes of choline and betaine are associated with a lower risk of primary liver cancer: a case-control study." Sci Rep 7(1): 679.

Higher betaine intake tended to be associated (only a trend p=0.08) with a decreased risk of coronary heart disease mortality in Japanese men after controlling for covariates.

Background: Dietary intakes of betaine and choline may reduce the risk of cardiovascular disease; however, epidemiologic evidence is limited. Seafood is a rich source of betaine and is a popular traditional food in Japan.Objective: We examined the associations of betaine and choline intakes with cardiovascular disease mortality in a population-based cohort study in Japan.
Methods: Study subjects were 13,355 male and 15,724 female residents of Takayama City, Japan, who were aged ≥35 y and enrolled in 1992. Their diets were assessed by a validated food frequency questionnaire. Deaths from coronary heart disease and stroke were identified from death certificates over 16 y.
Results: During follow-up, we documented 308 deaths from coronary heart disease and 676 deaths from stroke (393 from ischemic and 153 from hemorrhagic strokes). Compared with the lowest quartile, the second, third, and highest quartiles of betaine intake were significantly associated with a decreased risk of mortality from coronary heart disease in men after controlling for covariates. The HRs were 0.58 (95% CI: 0.36, 0.93), 0.62 (95% CI: 0.39, 0.998), and 0.60 (95% CI: 0.37, 0.97), respectively. The trend was not statistically significant (P = 0.08). There was no significant association between betaine intake and the risk of mortality from ischemic stroke. In women, betaine intake was unrelated to mortality from coronary heart disease and stroke (P = 0.32 and 0.73, respectively, for interaction by sex). There was no significant association between choline intake and cardiovascular disease mortality in men or women.
Conclusion: Overall, we found no clear evidence of significant associations between choline and betaine intakes and cardiovascular disease mortality in Japanese men and women.

Nagata, C., et al., Choline and Betaine Intakes Are Not Associated with Cardiovascular Disease Mortality in Japanese Men and Women. The Journal of Nutrition, 2015.

No association of betaine intake and peripheral artery disease

OBJECTIVE: Few studies have examined the roles of homocysteine and related nutrients in the development of peripheral artery disease (PAD). We examined the associations between plasma homocysteine, dietary B vitamins, betaine, choline, and supplemental folic acid use and incidence of PAD.
METHODS: We used two cohort studies of 72,348 women in the Nurses' Health Study (NHS, 1990-2010) and 44,504 men in the Health Professionals Follow-up Study (HPFS, 1986-2010). We measured plasma homocysteine in nested matched case-control studies of clinically recognized PAD within both cohorts, including 143 PAD cases and 424 controls within the NHS (1990-2010) and 143 PAD cases and 428 controls within the HPFS (1994-2008). We examined the association between diet and risk of incident PAD in the cohorts using a food frequency questionnaire and 790 cases of PAD over 3.1 million person-years of follow-up.
RESULTS: Higher homocysteine levels were positively associated with risk of PAD in men (adjusted IRR 2.17; 95% CI, 1.08-4.38 for tertile 3 vs. 1). There was no evidence of an association in women (adjusted IRR 1.14; 95% CI, 0.61-2.12). Similarly, higher folate intake, including supplements, was inversely associated with risk of PAD in men (adjusted HR 0.90; 95% CI, 0.82-0.98 for each 250 mug increase) but not women (HR 1.01, 95% CI, 0.88-1.15). Intakes of the other B vitamins, betaine, and choline were not consistently associated with risk of PAD in men or women.
CONCLUSION: Homocysteine levels were positively associated and dietary folate intake was inversely associated with risk of PAD in men but not in women.

Bertoia, M.L., et al., Plasma homocysteine, dietary B vitamins, betaine, and choline and risk of peripheral artery disease. Atherosclerosis, 2014. 235(1): p. 94-101

Individuals with high plasma concentrations of methionine, choline, and betaine may be at reduced risk of colorectal cancer

BACKGROUND: Disturbances in one carbon-metabolism may contribute to carcinogenesis by affecting methylation and synthesis of DNA. Choline and its oxidation product betaine are involved in this metabolism and can serve as alternative methyl group donors when folate status is low.
SUBJECTS AND METHODS: We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), to investigate plasma concentrations of the methyl donors methionine, choline, betaine (trimethylglycine), and dimethylglycine (DMG) in relation to colorectal cancer (CRC) risk. Our study included 1,367 incident CRC cases (965 colon; 402 rectum) and 2,323 controls matched by gender, age group, and study center. Multivariate-adjusted odds ratios (OR) and 95% confidence intervals (CI) for CRC risk were estimated by conditional logistic regression comparing the fifth to the first quintile of plasma concentrations.
RESULTS: Overall, methionine (OR: 0.79, 95%CI: 0.63-0.99, P-trend=0.05), choline (OR: 0.77, 95%CI: 0.60-0.99, P-trend=0.07), and betaine (OR: 0.85, 95%CI: 0.66-1.09, P-trend=0.06) concentrations were inversely associated with CRC risk of borderline significance. In participants with folate concentration below the median of 11.3 nmol/L, high betaine concentration was associated with reduced CRC risk (OR: 0.71, 95%CI: 0.50-1.00, P-trend=0.02), which was not observed for those having a higher folate status. Among women, but not men, high choline concentration was associated with decreased CRC risk (OR: 0.62, 95%CI: 0.43-0.88, P-trend=0.01). Plasma DMG was not associated with CRC risk.
CONCLUSIONS: Individuals with high plasma concentrations of methionine, choline, and betaine may be at reduced risk of colorectal cancer.

Nitter, M., et al., Plasma Methionine, Choline, Betaine, and Dimethylglycine, in relation to Colorectal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Ann Oncol, 2014

Dietary betaine may help prevent NTDs

BACKGROUND: Low maternal intake of dietary choline and betaine (a choline derivative) has recently been investigated as a possible risk factor for neural tube defects (NTDs)
METHODS: This case-control study examined the NTD risk associated with choline and betaine in 409 Mexican-American women who gave birth during 1995 to 2000 in the 14-county border region of Texas RESULTS: Using data from the food frequency questionnaire and the lowest quartiles of intake as the reference categories, a protective association was suggested between higher intakes of choline and betaine and NTD risk although the 95% confidence intervals for all risk estimates included 1.0. For choline intake in the second, third, and fourth quartiles, adjusted odds ratios were 1.2, 0.80, and 0.89, respectively. Betaine appeared more protective with odds ratios of 0.62, 0.73, and 0.61, respectively, for the second, third, and fourth quartiles of intake.
CONCLUSION: Study findings suggest that dietary betaine may help to prevent NTDs.

Lavery, A.M., et al., Dietary intake of choline and neural tube defects in Mexican Americans. Birth Defects Res A Clin Mol Teratol, 2014

Choline and betaine intakes are associated with reduced risk of nasopharyngeal carcinoma

Background: Intakes of choline and betaine have been inversely related to the risk of various neoplasms, but scant data exist on nasopharyngeal carcinoma (NPC). We examined the association between consumption of choline and betaine and risk of NPC.

Methods: We conducted a case-control study with 600 incident NPC patients and 600 controls 1 : 1 matched by age, sex and household type in Guangdong, China. Dietary intake was assessed by a food frequency questionnaire through face-to-face interview.

Results: Intakes of total choline, betaine and choline+betaine were inversely related to NPC after adjustment for various lifestyle and dietary factors. Adjusted odds ratios (95% CI) for quartile 4 (vs quartile 1) were 0.42 (0.29, 0.61) for total choline, 0.50 (0.35, 0.72) for betaine and 0.44 (0.30, 0.64) for betaine+total choline. Regarding various sources of choline, lower NPC risk was associated with greater intakes of choline from phosphatidylcholine, free choline, glycerophosphocholine and phosphocholine, but not sphingomyelin.

Conclusion: These findings are consistent with a beneficial effect of choline and betaine intakes on carcinogenesis.

Zeng, F.F., et al., Choline and betaine intakes are associated with reduced risk of nasopharyngeal carcinoma in adults: a case-control study. Br J Cancer, 2013

Lower level of serum betaine is associated with an increased risk of microangiopathy in diabetics

BACKGROUND: Diabetes represents one of the greatest medical and socioeconomic emergencies worldwide and pathogenesis involved is complicated. The effect of methyl donors and genetic polymorphisms in metabolic enzymes on the risk of microangiopathy in patients with diabetes is not well understood. This study aims to investigate the association of homocysteine, choline, and betaine levels and phosphatidylethanolamine N-methyltransferase (PEMT) G774C (rs12325817) genotypes with the risk of diabetes and its related microangiopathic complications.
METHODS: Between January 2009 and June 2010, 184 diabetic patients and 188 non-diabetic control subjects were enrolled in the hospital-based case-control study. Serum concentrations of betaine and choline were determined by high performance liquid chromatography-mass spectrometry (HPLC-MS). Serum concentration of homocysteine was assayed using HPLC. PEMT gene mutations were detected by polymerase chain reaction and restriction fragment length polymorphism.
RESULTS: After adjustment for the potential confounders, serum total homocysteine had a significant dose-dependent positive association, and serum choline had an inverse association with the risks of diabetes and its microangiopathic complications (both p < 0.001). Although serum betaine was not associated with the risk of diabetes, it had a significant inverse association with diabetic microangiopathy. Compared with GG genotype, the CC genotype of PEMT G774C was associated with a decreased risk of diabetes (OR 0.559, 95%CI 0.338, 0.926) and its microangiopathy (OR 0.452, 95%CI 0.218, 0.937).
CONCLUSION: The GG genotype of the PEMT G774C polymorphism, higher level of serum homocysteine, and lower level of serum betaine are associated with an increased risk of microangiopathy in patients with diabetes.

Chen, L., et al., Higher homocysteine and lower betaine increases the risk of microangiopathy in patients with diabetes mellitus carrying the GG genotype of PEMT G774C. Diabetes Metab Res Rev, 2013

Dietary Choline and Betaine Intakes Vary in an Adult Multiethnic Population

Choline and betaine are important nutrients for human health, but reference food composition databases for these nutrients became available only recently. We tested the feasibility of using these databases to estimate dietary choline and betaine intakes among ethnically diverse adults who participated in the Multiethnic Cohort (MEC) Study. Of the food items (n = 965) used to quantify intakes for the MEC FFQ, 189 items were exactly matched with items in the USDA Database for the Choline Content of Common Foods for total choline, choline-containing compounds, and betaine, and 547 items were matched to the USDA National Nutrient Database for Standard Reference for total choline (n = 547) and 148 for betaine. When a match was not found, choline and betaine values were imputed based on the same food with a different form (124 food items for choline, 300 for choline compounds, 236 for betaine), a similar food (n = 98, 284, and 227, respectively) or the closest item in the same food category (n = 6, 191, and 157, respectively), or the values were assumed to be zero (n = 1, 1, and 8, respectively). The resulting mean intake estimates for choline and betaine among 188,147 MEC participants (aged 45-75) varied by sex (372 and 154 mg/d in men, 304 and 128 mg/d in women, respectively; P-heterogeneity < 0.0001) and by race/ethnicity among Caucasians, African Americans, Japanese Americans, Latinos, and Native Hawaiians (P-heterogeneity < 0.0001), largely due to the variation in energy intake. Our findings demonstrate the feasibility of assessing choline and betaine intake and characterize the variation in intake that exists in a multiethnic population.

Yonemori, K.M., et al., Dietary Choline and Betaine Intakes Vary in an Adult Multiethnic Population. J Nutr, 2013

Estimation of usual intake and food sources of choline and betaine in New Zealand reproductive age women

Recently, choline has been associated with neurodevelopment, cognitive function and neural tube defect incidence. However, data on usual intakes are limited, and estimates of dietary intakes of choline and its metabolite betaine, are not available for New Zealanders. The objective of the present study was to determine usual intake and food sources of choline and betaine in a group of New Zealand reproductive age women. Dietary intake data were collected from a sample of 125 women, aged 18-40 years, by means of a 3-day weighed food record, and usual choline and betaine intake distributions were determined. The mean (SD) daily intakes of choline and betaine were 316 (66) mg and 178 (66) mg, respectively. The total choline intake relative to energy intake and body weight was 0.18 mg/kcal and 5.1 mg/kg, respectively. Only 16% of participants met or exceeded the Adeuate Intake (AI) for adult women of 425 mg of choline. The top five major food contributors of choline were eggs, red meat, milk, bread and chicken; and of betaine were bread, breakfast cereal, pasta, grains and root vegetables (carrots, parsnips, beetroot, swedes). Our findings contribute towards the recent emergence of published reports on the range of dietary choline and betaine intakes consumed by free-living populations. In our sample of New Zealand women, few participants were meeting or exceeding the AI level. Given recent epidemiological evidence suggesting health benefits of increased choline and betaine intakes, recommendations should be made to encourage the consumption of choline and betaine-rich foods.

Mygind, V.L., et al., Estimation of usual intake and food sources of choline and betaine in New Zealand reproductive age women. Asia Pac J Clin Nutr, 2013. 22(2): p. 319-24

Higher betaine intake may be protective against lung cancer through mitigating the adverse effect of smoking

Evidence from human and animal research indicates that choline metabolic pathways may be activated during a variety of diseases, including cancer. We report results of a case-control study of 2821 lung cancer cases and 2923 controls that assessed associations of choline and betaine dietary intakes with lung cancer. Using multivariable logistic regression analyses, we report a significant association between higher betaine intake and lower lung cancer risk that varied by smoking status. Specifically, no significant association was observed between betaine intake and lung cancer among never-smokers. However, higher betaine intake was significantly associated with reduced lung cancer risk among smokers, and the protective effect was more evident among current than former smokers: for former and current smokers, the ORs (95% CI) of lung cancer for individuals with highest as compared to lowest quartiles of intake were 0.70(0.55-0.88) and 0.51(0.39-0.66) respectively. Significant linear trend of higher betaine intake and lower lung cancer risk was observed among both former and current smokers. A similar protective effect was also observed with choline intake both in overall analysis as well as among current smokers, with p-values for chi-square tests being 0.001 and 0.004 respectively, but the effect was less evident, as no linear trend was observed. Our results suggest that choline and betaine intake, especially higher betaine intake, may be protective against lung cancer through mitigating the adverse effect of smoking.

Ying, J., et al., Associations between Dietary Intake of Choline and Betaine and Lung Cancer Risk. PLoS One, 2013. 8(2): p. e54561

Maternal intake of methyl-donor nutrients and child cognition

Methyl-donor nutrients are substrates for methylation reactions involved in neurodevelopment processes. The role of maternal intake of these nutrients on cognitive performance of the offspring is poorly understood. We examined the associations of maternal intake of folate, vitamin B12, choline, betaine and methionine during the first and second trimesters of pregnancy, with tests of cognitive performance in the offspring at 3 years of age using data from 1210 participants in Project Viva, a prospective pre-birth cohort study in Massachusetts. We assessed nutrient intake with the use of food frequency questionnaires. Children's cognition at age 3 years was evaluated with the Peabody Picture Vocabulary Test III (PPVT-III) and visual-motor skills with the Wide Range Assessment of Visual Motor Abilities test. In multivariable models adjusting for potential sociobehavioural and nutritional confounders, for each 600 microg/day increment in total folate intake during the first trimester, PPVT-III score at age 3 years was 1.6 points [95% confidence interval (CI) 0.1, 3.1; P = 0.04] higher. There was a weak inverse association between vitamin B12 intake during the second trimester and PPVT-III scores [-0.4 points per 2.6 microg/day; 95% CI -0.8, -0.1; P = 0.01]. We did not find associations between choline, betaine or methionine and cognitive outcomes at this age. Results of this study suggest that higher intake of folate in early pregnancy is associated with higher scores on the PPVT-III, a test of receptive language that predicts overall intelligence, at age 3 years.

In unadjusted analyses, intake of folate and betaine during the first or second trimester was directly related to PPVT-III scores. After adjustment for potential socio-economic, educational and dietary confounders, however, the associations with both nutrients were attenuated and only the relationship between folate intake during the first trimester and PPVT-III scores remained statistically significant.

Villamor, E., et al., Maternal intake of methyl-donor nutrients and child cognition at 3 years of age. Paediatr Perinat Epidemiol, 2012. 26(4): p. 328-35.

Dietary choline and betaine intakes and risk of cardiovascular diseases: review of epidemiological evidence

BACKGROUND: Cardiovascular diseases (CVD) are the most important causes of human mortality in the world. Higher intakes of choline and betaine have been shown to be associated with lower plasma homocysteine levels (the putative CVD risk factor). This study aimed to review the evidence on the association between dietary intakes of choline and betaine and traditional/novel CVD risk factors.

METHODS: We searched in PubMed website from 1990 to 2009, with the use of following keywords: "dietary choline and betaine, cardiovascular diseases, metabolic syndrome, inflammation". The cross-sectional and prospective studies as well as the clinical trials were recruited in this investigation.

RESULTS: Dietary intakes of “choline”/“choline and betaine” were not significantly associated with CVD risk; however, the higher intakes of choline and betaine were associated with higher serum concentrations of CRP, IL-6 and TNF-α. Individuals with high plasma choline levels were obese and had elevated plasma triglycerides, HDL and non-HDL cholesterol levels; whereas high plasma betaine levels were inversely associated with these biochemical markers. Both choline and betaine supplementation resulted in increased blood lipid profiles.

CONCLUSION: Although dietary intakes of choline and betaine were not significantly associated with CVD incidence, the long-term consumption of these nutrients have been shown to prevent CVD mortality by decreasing inflammation and other risk factors.

Rajaie, S. and A. Esmaillzadeh, Dietary choline and betaine intakes and risk of cardiovascular diseases: review of epidemiological evidence. ARYA Atheroscler, 2011. 7(2): p. 78-86

Choline and betaine food sources and intakes in Taiwanese

Choline and betaine are involved in several similar health-relevant metabolic pathways, but the foods sources are different. We have assessed their intakes (individual, sums and ratios) from a dominantly Chinese food cultural point of view. A representative free-living Taiwanese population aged 13-64 years was drawn from the Nutrition and Health Survey in Taiwan (NAHSIT) 1993-1996. Food intake was derived from interviews as 24-hour recalls. The USDA database, with adaptations for Taiwan, provided choline and betaine food compositions. Major food contributors of these nutrients were identified and compared with data from the US Framingham offspring study. Mean and variance reduced median nutrient intakes were calculated. Top ten major food contributors of choline in Taiwan were eggs, pork, chicken, fish, soybean and its products, dark leafy vegetables, dairy, fruit, wheat products and light leafy vegetables in sequence. For betaine, the top ten were dark leafy vegetables, wheat products, fish, pork, bread, chicken, cake/cookies, grain-based alcoholic beverages, rice and its products and sauces. The main contributors of choline in Taiwan and the USA were, respectively, eggs and red meat; and for betaine, greens were similarly best contributor. The rankings of the main food contributors of choline and betaine differed substantially between Taiwan and the USA. The total daily intakes (mean+/-SE, mg) in Taiwan for choline were 372+/-19 (median=348) in men and 265+/-9 (median 261) for women; for betaine, values were 101+/-3 (median 93) in men and 78+/-8 (median 76) for women. These allow for health outcome considerations.
Chu, D.M., et al., Choline and betaine food sources and intakes in Taiwanese. Asia Pac J Clin Nutr, 2012. 21(4): p. 547-57

High dietary betaine intake associated with less advanced AMD

Objective
We evaluated monozygotic twin pairs with discordant age-related macular degeneration (AMD) phenotypes to assess differences in behavioral and nutritional factors.

Design
Case series.

Participants
Caucasian male twin pairs from the United States Twin Study of Macular Degeneration.

Methods
Twin pairs were genotyped to confirm monozygosity. Ocular characteristics were evaluated based on fundus photographs using the Wisconsin Grading System and a 5-grade Clinical Age-Related Maculopathy Staging System. We selected twin pairs discordant in each of the following phenotypic categories: Stage of AMD (n = 28), drusen area (n = 60), drusen size (n = 40), and increased pigment area (n = 56). The Wilcoxon signed-rank test and linear regression were used to assess associations between behavioral and nutritional characteristics and each phenotype within discordant twin pairs.

Main Outcome Measures
Differences in smoking and dietary factors within twin pairs discordant for stage of AMD, drusen area, drusen size, and pigment area.

Results
Representative fundus photographs depict the discordant phenotypes. Pack-years of smoking were higher for the twin with the more advanced stage of AMD (P = 0.05). Higher dietary intake of vitamin D was present in the twins with less severe AMD (P = 0.01) and smaller drusen size (P = 0.05) compared with co-twins, adjusted for smoking and age. Dietary intakes of betaine and methionine were significantly higher in the twin with lower stage of AMD (P = 0.009) and smaller drusen area (P = 0.03), respectively.

Conclusions
The twin with the more advanced stage of AMD, larger drusen area, drusen size, and pigment area tended to be the heavier smoker. The twin with the earlier stage of AMD, smaller drusen size and area, and less pigment tended to have higher dietary vitamin D, betaine, or methionine intake. Results suggest that behavioral and nutritional factors associated with epigenetic mechanisms are involved in the etiology of AMD, in addition to genetic susceptibility.

Seddon, J.M., et al., Smoking, dietary betaine, methionine, and vitamin D in monozygotic twins with discordant macular degeneration: epigenetic implications. Ophthalmology, 2011. 118(7): p. 1386-94.

High dietary betaine reduces risk of Barrett's esophagus

Folate plays a key role in DNA synthesis and methylation. Limited evidence suggests high intake may reduce risks of esophageal cancer overall; however, associations with esophageal cancer subtypes and Barrett's esophagus (BE), a precancerous lesion, remain unexplored.

We evaluated the relation between intake of folate, B vitamins, and methyl-group donors (methionine, choline, betaine) from foods and supplements, polymorphisms in key folate-metabolizing genes, and risk of BE, esophageal adenocarcinoma (EAC), and esophageal squamous cell carcinoma (ESCC) in 2 population-based case-control studies in Australia. BE patients without (n = 266) or with (n = 101) dysplasia were compared with population controls (n = 577); similarly, EAC (n = 636) or ESCC (n = 245) patients were compared with population controls (n = 1507) using multivariable adjusted logistic regression. Increasing intake of folate from foods was associated with reduced EAC risk (P-trend = 0.01) and mitigated the increased risks of ESCC associated with smoking and alcohol consumption. In contrast, high intake of folic acid from supplements was associated with a significantly elevated risk of BE with dysplasia. High intakes of riboflavin and methionine from food were associated with increased EAC risk, whereas increasing betaine intake was associated with reduced risks of BE without (P-trend = 0.004) or with dysplasia (P-trend = 0.02). Supplemental thiamin, riboflavin, niacin, and vitamin B-12 were associated with increased EAC risk. There were no consistent associations between genetic polymorphisms studied and BE or EAC risk. High intake of folate-containing foods may reduce risk of EAC, but our data raise the possibility that folic acid supplementation may increase risks of BE with dysplasia and EAC.

Ibiebele, T.I., et al., High intake of folate from food sources is associated with reduced risk of esophageal cancer in an Australian population. J Nutr, 2011. 141(2): p. 274-83.

Colorectal cancer

This study prospectively examined the associations between dietary choline and betaine intake and risk of colorectal cancer in men in the Health Professionals Follow-up Study. They did not find any statistically significant associations between choline intake or betaine intake and risk of colorectal cancer. Comparing the top quintile with bottom quintile, multivariate relative risks (95% confidence interval) were 0.97 (0.79-1.20; Ptrend = 0.87) for choline intake and 0.94 (0.77-1.16; Ptrend = 0.79) for betaine intake.

Lee et al (2010). "Choline and Betaine Intake and the Risk of Colorectal Cancer in Men." Cancer Epidemiology Biomarkers & Prevention 19(3):1-4

Breast cancer risk

This study examined the intake of choline and betaine and breast cancer risk among 74, 584 post-menopausal women in the Nurses’ Health Study. Overall, choline (mean±s.d.; 326±61 mg per day) and betaine (104±33 mg per day) intake was not associated with a reduced risk of post-menopausal breast cancer.

Cho E, Holmes MD, Hankinson SE, Willett WC: Choline and betaine intake and risk of breast cancer among post-menopausal women. Br J Cancer 2010:Epub Jan 2010.

Ovarian cancer risk

The authors prospectively examined the relationship between the intake of choline/betaine and ovarian cancer risk among participants from the Nurses' Health Study (NHS) and NHSII. There were no associations between total choline, betaine, as well as choline plus betaine intake and ovarian cancer risk. Results did not vary by alcohol consumption, folate intake or after the exclusion of cases diagnosed during the 4-year period after dietary assessment.

Kotsopoulos et al (2010). "Dietary betaine and choline intake are not associated with risk of epithelial ovarian cancer." Eur J Clin Nutr 64(1): 111-114.

Fibrates may cause abnormal urinary betaine loss

Abnormal urinary loss of betaine is common in patients with the metabolic syndrome or diabetes mellitus. These patients are often treated with fibrates which alter renal function and raise plasma homocysteine concentrations.

- patients taking bezafibrate had higher betaine excretion than patients not taking fibrates
- of 32 patients taking bezafibrate, 20 had abnormal (>97.5 %-ile) betaine excretion
- plasma homocysteine correlated positively with betaine excretion in male patients with lipid disorders who were not taking fibrate, but the relationship was stronger if patients taking bezafibrate were included
- in elderly (>65 years) subjects with hypertension there was a similar correlation, which was stronger when a subject taking bezafibrate was included

Abnormal betaine excretion is common in patients treated with bezafibrate. Bezafibrate appears to exacerbate betaine loss, which will cause a rise in plasma homocysteine. Betaine supplementation could be considered in conjunction with fibrate therapy.

Lever et al (2009). "Fibrates may Cause an Abnormal Urinary Betaine Loss Which is Associated with Elevations in Plasma Homocysteine." Cardiovasc Drugs Ther. Epub Aug 4

Reduced breast cancer risk and mortality

The authors investigated the associations of dietary intakes of choline and betaine and breast cancer risk and mortality in the population-based Long Island Breast Cancer Study Project.

- there was an indication that a higher intake of free choline was associated with reduced risk of breast cancer
- higher intakes of betaine, phosphocholine, and free choline were associated with reduced all-cause as well as breast cancer-specific mortality in a dose-dependent fashion
- the betaine-homocysteine methyltransferase gene (BHMT) rs3733890 polymorphism was associated with reduced breast cancer-specific mortality

The study suggests that high intake of betaine and choline may be a promising strategy to prevent the development of breast cancer and to reduce its mortality.

Xu et al (2009). "High intakes of choline and betaine reduce breast cancer mortality in a population-based study". FASEB J., epub July 27.