-
1.
Lipid Intake and Breast Cancer Risk: Is There a Link? A New Focus and Meta-Analysis.
Lodi, M, Kiehl, A, Qu, FL, Gabriele, V, Tomasetto, C, Mathelin, C
European journal of breast health. 2022;18(2):108-126
-
-
-
-
Free full text
Plain language summary
Incidence of breast cancer is the leading cause of cancer-related mortality, accounting for 15.5% of all cancer-related deaths. However, there is a lack of complete understanding of the effects of different types of dietary lipids on breast cancer development, such as saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), dietary cholesterol, polyunsaturated fatty acids (PUFA), and unsaturated trans fatty acids (TFA). An evaluation of the effect of lipid consumption on breast cancer and the impact it has on menopausal status was conducted in this meta-analysis, which included forty-four studies. Increased saturated fatty acid intake was associated with an increased risk of breast cancer in postmenopausal women. However, breast cancer risk was not associated with increased consumption of total fat, SFA, MUFA, PUFA, and cholesterol in premenopausal women. The effects of estrogen and the release of proinflammatory cytokines by adipocytes should be evaluated, as well as other pathways that contribute to the development of breast cancer. There is a need for further robust studies to evaluate the effects of different types of lipid consumption on breast cancer. Although the association between SFA and breast cancer is weak, healthcare professionals can use this study's findings to better understand the detrimental effect of SFA, despite the fact that there is a great deal of heterogeneity in the current analysis.
Expert Review
Conflicts of interest:
None
Take Home Message:
- The authors found no association between total fat, saturated fatty-acids, mono and poly-unsaturated fatty acids and cholesterol intake and breast cancer incidence in the general population and in pre-menopausal women.
Evidence Category:
-
X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
-
B: Systematic reviews including RCTs of limited number
-
C: Non-randomized trials, observational studies, narrative reviews
-
D: Case-reports, evidence-based clinical findings
-
E: Opinion piece, other
Summary Review:
- Among lifestyle-related breast cancer risk factors, the role of diet in breast cancer remains uncertain.
- The authors highlight a weak association between high SFA consumption and breast cancer risk in post-menopausal women.
- The authors found no association between total fat, saturated fatty-acids, mono and poly-unsaturated fatty acids and cholesterol intake and breast cancer incidence in the general population and in pre-menopausal women.
Objectives
- To determine if there is an association between total lipid intake, saturated fatty acid (SFA), Poly- and Mono-Unsaturated Fatty Acid (PUFA and MUFA) and cholesterol intake and breast cancer risk.
Results
- Forty-four articles were included in the meta-analysis, consisting of 28 case-control studies and 16 cohort studies.
- In total, this meta-analysis involved 1,185,896 women, of whom 54,553 had breast cancer.
- There was no association between total fat, SFA, MUFA, PUFA and cholesterol intake and breast cancer in the general population and in pre-menopausal women.
- In postmenopausal women, high SFA consumption was associated with increased breast cancer risk in case-control studies [relative risk (RR): 1.12; confidence interval (CI) 95%: 1.03–1.21; p = 0.006 but not in cohort studies (RR: 1.01; CI 95%: 0.85–1.19; p = 0.93).
Limitations
- Studies included in the meta-analysis were carried out on populations from five continents with significant cultural and dietary diversity, and well as different types of oils used in the diet
Conclusion
- At this stage, the authors state it is not possible to establish nutritional recommendations regarding the consumption of lipids to decrease breast cancer risk.
Clinical practice applications:
- The results of this meta-analysis does not demonstrate a statistically significant link between high consumption of total lipids, PUFA, MUFA and cholesterol and the occurrence of breast cancer.
- However, the results suggest that there is an association between SFA intake and breast cancer risk in postmenopausal women, although this was only found in case-controlled studies and not cohort studies.
- While obesity is a known breast cancer risk factor after menopause, the link between the effect of diet and the effect of obesity on the breast may be through different mechanisms.
- The authors investigated if high lipid consumption acts on breast tissue by the same mechanisms as obesity, and found the association between SFA intake and breast cancer risk in postmenopausal women must be through other biological explanations.
- The authors found that while high SFA consumption may increase breast cancer risk among post-menopausal women, biological mechanisms linking SFA and breast cancerogenesis are still unknown.
- The meta-analysis found high blood cholesterol levels appear to increase the risk of breast cancer. However, the authors could not confirm that high dietary cholesterol intake is a risk factor for breast cancer. The authors postulated this may be in part due to the low proportion of cholesterol (about 30%) in the diet, while the rest comes from the degradation of lipids and carbohydrates by the liver.
Considerations for future research:
- As lipids can have different actions in the same family, studies should rather focus on specific lipid consumption
Abstract
Objective: To determine if there is an association between total lipid intake, saturated fatty acid (SFA), Poly- and Mono-Unsaturated Fatty Acid (PUFA and MUFA) and cholesterol intake and breast cancer risk. Materials and Methods: We conducted a systematic review of the literature and a meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We included all cohort and case-control studies published up to December 2020 with subgroup analysis according to menopausal status. Results: We included 44 articles for analysis. There was no association between total fat, SFA, MUFA, PUFA and cholesterol intake and breast cancer in the general population and in pre-menopausal women. In postmenopausal women, high SFA consumption was associated with increased breast cancer risk in case-control studies [relative risk (RR): 1.12; confidence interval (CI) 95%: 1.03-1.21; p = 0.006 but not in cohort studies (RR: 1.01; CI 95%: 0.85-1.19; p = 0.93). Conclusion: There was a weak association between high SFA consumption and breast cancer risk in post-menopausal women, however there was high heterogeneity for this analysis. As lipids can have different actions in the same family, studies should rather focus on specific lipid consumption.
-
2.
Associations between Digital Health Intervention Engagement and Dietary Intake: A Systematic Review.
Delaney, T, Mclaughlin, M, Hall, A, Yoong, SL, Brown, A, O'Brien, K, Dray, J, Barnes, C, Hollis, J, Wyse, R, et al
Nutrients. 2021;13(9)
-
-
-
Free full text
Plain language summary
Digital health interventions (DHIs) are a cost-effective way of delivering public health programs. Current evidence on the effectiveness of DHIs on behaviour change is inconclusive, yet many public health nutrition strategies rely on this modality. The aim of this review is to assess the literature on the efficacy on user engagement and improvements in dietary intake. This review included seven studies and showed supportive yet inconsistent results. The lack of user engagement was shown to be the primary limiting factor. Based on these results, the authors conclude DHIs can be an effective tool when used in conjunction with mixed-method approaches as health behaviour change is nuanced and non-linear. They acknowledge further qualitative research is required to better understand the relationship between DHIs, engagement, and improvements in dietary intake.
Abstract
There has been a proliferation of digital health interventions (DHIs) targeting dietary intake. Despite their potential, the effectiveness of DHIs are thought to be dependent, in part, on user engagement. However, the relationship between engagement and the effectiveness of dietary DHIs is not well understood. The aim of this review is to describe the association between DHI engagement and dietary intake. A systematic search of four electronic databases and grey literature for records published before December 2019 was conducted. Studies were eligible if they examined a quantitative association between objective measures of engagement with a DHI (subjective experience or usage) and measures of dietary intake in adults (aged ≥18 years). From 10,653 citations, seven studies were included. Five studies included usage measures of engagement and two examined subjective experiences. Narrative synthesis, using vote counting, found mixed evidence of an association with usage measures (5 of 12 associations indicated a positive relationship, 7 were inconclusive) and no evidence regarding an association with subjective experience (both studies were inconclusive). The findings provide early evidence supporting an association between measures of usage and dietary intake; however, this was inconsistent. Further research examining the association between DHI engagement and dietary intake is warranted.
-
3.
Depressive Symptoms in Middle-Aged and Elderly Women Are Associated with a Low Intake of Vitamin B6: A Cross-Sectional Study.
Odai, T, Terauchi, M, Suzuki, R, Kato, K, Hirose, A, Miyasaka, N
Nutrients. 2020;12(11)
-
-
-
Free full text
Plain language summary
Depression and anxiety are common mental disorders, which are more prominent in women undergoing menopause. Large hormonal fluctuations are thought to be the driving factor, however treatments for this may have side effects such as heart disease and cancer. Interest in complementary therapies has increased and associations between several nutrients and mental health disorders has been reported, however their affects in perimenopausal and post-menopausal women is still unknown. This cross-sectional study of 289 women aged 40 and over aimed to look at associations between dietary nutrient consumption and anxiety/depressive symptoms. The results showed that over half of the women reported some symptoms of anxiety or depression. Of the 43 nutrients examined, only decreased vitamin B6 intake was associated with symptoms of moderate-severe depression but not symptoms of anxiety. It was concluded that moderate to severe depressive symptoms were associated with a lower dietary intake of vitamin B6. However, it should be noted that dietary intake and not serum levels were used to make associations. This study could be used by healthcare professionals to recommend increased dietary vitamin B6 intake for symptoms of moderate to severe depression in women aged 40 or over.
Abstract
This study investigated the nutritional factors that are associated with anxiety and depressive symptoms in Japanese middle-aged and elderly women. We conducted a cross-sectional study with 289 study participants aged ≥40 years (mean age = 52.0 ± 6.9 years). Their dietary habits, menopausal status and symptoms, and varied background factors, such as body composition, lifestyle factors, and cardiovascular parameters, were assessed. Their anxiety and depressive symptoms were evaluated using the Hospital Anxiety and Depression Scale (HADS), where scores of 0-7 points, 8-10 points, and 11-21 points on either the anxiety or depression subscales were categorized as mild, moderate, and severe, respectively. The dietary consumption of nutrients was assessed using a brief self-administered diet history questionnaire. The relationships between the moderate-to-severe anxiety/depressive symptoms and the dietary intake of 43 major nutrients were investigated using multivariate logistic regression analyses. After adjusting for age, menopausal status, and the background factors that were significantly related to depressive symptoms, moderate and severe depression was significantly inversely associated with only vitamin B6 (adjusted odds ratio per 10 μg/MJ in vitamin B6 intake = 0.89, 95% confidence interval = 0.80-0.99). A higher intake of vitamin B6 could help relieve depressive symptoms for this population.
-
4.
One- and Two-Year Effects of the Healthy Primary School of the Future on Children's Dietary and Physical Activity Behaviours: A Quasi-Experimental Study.
Bartelink, NHM, van Assema, P, Kremers, SPJ, Savelberg, HHCM, Oosterhoff, M, Willeboordse, M, van Schayck, OCP, Winkens, B, Jansen, MWJ
Nutrients. 2019;11(3)
-
-
-
Free full text
Plain language summary
Diet and Physical Activity (PA) habits are formed at a young age, and unhealthy habits can lead to childhood obesity and lifelong health problems. Schools are globally recognised as having access to children across all socio-economic backgrounds and to play an important role in influencing healthy habits. This Dutch experimental longitudinal study looks at the impact Primary schools can have on the health of their students by implementing a dedicated Nutrition and PA Program called ‘Healthy Primary Schools for the Future (HPSF), modelled on an American initiative, piloted in 4 schools and 2 control schools. The study tests whether a fully implemented program (focused on Nutrition and PA - including free lunches & daily PA sessions) or a partial program (focused only on PA sessions) influences healthy change in children’s behaviours versus control schools (no program). The data from 1676 children aged 4-12 yrs was used and the study took place over 3 yrs (2015-2017) with a commitment to continue till 2019 where follow-up data could be obtained. The data was collected once a year using parental and child questionnaires. Additional movement data was obtained from accelerometers the children wore for 7 days during each annual measurement week. The results at year 3 show that a combined nutrition and PA program had greatest benefits on improving diet (variety of foods eaten), and reducing unhealthy snacking, and increasing PA. Neither the partial program or control schools displayed positive changes. The researchers reflect that the full program allowed greater involvement from all parties involved (schools, parents, children’s, educational and health partners) which led to changes becoming an integral part of the school routine. Focusing on nutrition and PA together seemed to encourage complementary behavioural changes compared to focusing only on PA.
Abstract
Schools can help to improve children's health. The 'Healthy Primary School of the Future' (HPSF) aims to sustainably integrate health and well-being into the school system. This study examined the effects of HPSF on children's dietary and physical activity (PA) behaviours after 1 and 2 years' follow-up. The study (n = 1676 children) has a quasi-experimental design with four intervention schools, i.e., two full HPSF (focus: nutrition and PA) and two partial HPSF (focus: PA), and four control schools. Accelerometers and child- and parent-reported questionnaires were used at baseline, after 1 (T1) and 2 (T2) years. Mixed-model analyses showed significant favourable effects for the full HPSF versus control schools for, among others, school water consumption (effect size (ES) = 1.03 (T1), 1.14 (T2)), lunch intake of vegetables (odds ratio (OR) = 3.17 (T1), 4.39 (T2)) and dairy products (OR = 4.43 (T1), 4.52 (T2)), sedentary time (ES = -0.23 (T2)) and light PA (ES = 0.22 (T2)). Almost no significant favourable effects were found for partial HPSF compared to control schools. We conclude that the full HPSF is effective in promoting children's health behaviours at T1 and T2 compared with control schools. Focusing on both nutrition and PA components seems to be more effective in promoting healthy behaviours than focusing exclusively on PA.
-
5.
Association of Folate and Vitamins Involved in the 1-Carbon Cycle with Polymorphisms in the Methylenetetrahydrofolate Reductase Gene (MTHFR) and Global DNA Methylation in Patients with Colorectal Cancer.
Ferrari, A, Torrezan, GT, Carraro, DM, Aguiar Junior, S
Nutrients. 2019;11(6)
-
-
-
Free full text
Plain language summary
This 2012 cross-sectional observational study examines the role of epigenetic gene expression and methylation in 189 patients with colorectal adenocarcinoma, including 128 with MTHFR polymorphisms. The mean age was 61 years and there was a 50/50 gender split. The focus nutrients were folate, vitamins B2, B6, B12, choline, betaine, and methionine, all of which are known to be essential nutrients for DNA synthesis and more specifically have a key role in the 1-carbon cycle, and S-adenosylmethionine (SAM). The study is based on prospective data collection from food frequency and clinical evaluation questionnaires, and blood work. There does not appear to have been any control group or blinding of processes (at least not reported in the study). The results showed that serum folate levels were positively correlated with the equivalent total dietary folate intake and global DNA methylation. No significant differences were found between serum folate levels in relation to the different genotypes of MTHFR polymorphisms such as C677T. A weak association was found between the A1298C polymorphism and lower levels of methylation. No significant findings were reported for the vitamins used in the study. The study concludes that folate intake, serum folate levels, global DNA methylation and age were predictors of clinicopathological staging.
Abstract
Folate, vitamin B2, vitamin B6, vitamin B12, choline, and betaine are nutrients involved in the 1-carbon cycle that can alter the levels of DNA methylation and influence genesis and/or tumor progression. Thus, the objective of this study was to evaluate the association of folate and vitamins involved in the 1-carbon cycle and MTHFR polymorphisms in global DNA methylation in patients with colorectal cancer gene. The study included 189 patients with colorectal adenocarcinoma answering a clinical evaluation questionnaire and the Food Frequency Questionnaire (FFQ) validated for patients with colon and rectal cancer. Blood samples were collected for evaluation of MTHFR gene polymorphisms in global DNA methylation in blood and in tumor. The values for serum folate were positively correlated with the equivalent total dietary folate (total DFE) (rho = 0.51, p = 0.03) and global DNA methylation (rho = 0.20, p = 0.03). Individuals aged over 61 years (p = 0.01) in clinicopathological staging III and IV (p = 0.01) and with + heterozygous mutated homozygous genotypes for the MTHFR A1298C gene had higher levels of global DNA methylation (p = 0.04). The association between dietary intake of folate, serum folate, and tumor stage were predictive of global DNA methylation in patients' blood. The levels of serum folate, the dietary folate and the status of DNA methylation can influence clinicopathological staging.
-
6.
Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer's disease.
Patrick, RP
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2019;33(2):1554-1564
-
-
-
Free full text
-
Plain language summary
Alzheimer’s disease (AD) is a neurodegenerative disorder characterised by progressive memory loss, spatial disorientation, cognitive impairment and behavioural changes. Ageing is the main risk factor for AD, with approximately one-third of Americans over the age of 85 being affected by the condition. The APOE gene provides instructions for making the apolipoprotein E family of proteins that are involved in fat metabolism and cholesterol transport. There are three different variants of this gene, one inherited from each parent. The variant called APOE4 is thought to increase AD risk from 2-3-fold (one inherited copy) to as much as 15-fold (two inherited copies), compared to individuals who do not carry this variant. The omega-3 oil docosahexaenoic acid (DHA) is an essential fatty acid, which comprises approximately 30% of the fats found in the human brain. Low levels of DHA in the brain increase the risk of developing AD, while normal and high levels may prevent the condition and ameliorate symptoms. This review paper brings together several lines of evidence on why individuals with the APOE4 gene variant don’t respond well to DHA supplementation but experience positive effects from dietary intake of DHA. The author suggests that this is due to the different forms of DHA found in dietary and supplemental sources. Some of the DHA present in fish and seafood is in phospholipid form, which is metabolised into lysophosphatidylcholine DHA (DHA-lysoPC) in the body. In contrast, fish oil supplements contain no DHA in phospholipid form, but in other forms that are mostly metabolised to free DHA. This paper puts forward an argument that, due to the breakdown of the integrity of the blood-brain barrier, APOE4 carriers have impaired brain transport of free DHA but not DHA-lysoPC. The author concludes that dietary sources that contain high amounts of DHA in phospholipid form, such as fish and fish roe may help increase plasma levels of DHA-lysoPC, which may be better transported to the brains of APOE4 carriers. She also highlights the pressing need for future clinical trials to evaluate the effects of omega-3 oils in phospholipid form on the cognitive function of APOE4 carriers with AD.
Abstract
Dietary and supplemental intake of the ω-3 fatty acid docosahexaenoic acid (DHA) reduces risk of Alzheimer's disease (AD) and ameliorates symptoms. The apolipoprotein E ( APOE) 4 allele is the strongest risk factor for sporadic AD, exclusive of age. APOE4 carriers respond well to the DHA present in fish but do not respond as well to dietary supplements. The mechanisms behind this varied response remain unknown. I posit that the difference is that fish contain DHA in phospholipid form, whereas fish oil supplements do not. This influences whether DHA is metabolized to nonesterified DHA (free DHA) or a phospholipid form called lysophosphatidylcholine DHA (DHA-lysoPC). Free DHA is transported across the outer membrane leaflet of the blood-brain barrier (BBB) via passive diffusion, and DHA-lysoPC is transported across the inner membrane leaflet of the BBB via the major facilitator superfamily domain-containing protein 2A. I propose that APOE4 carriers have impaired brain transport of free DHA but not of DHA-lysoPC, as a consequence of a breakdown in the outer membrane leaflet of the BBB, putting them at increased risk for AD. Dietary sources of DHA in phospholipid form may provide a means to increase plasma levels of DHA-lysoPC, thereby decreasing the risk of AD.-Patrick, R. P. Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer's disease.
-
7.
Theoretical Food and Nutrient Composition of Whole-Food Plant-Based and Vegan Diets Compared to Current Dietary Recommendations.
Karlsen, MC, Rogers, G, Miki, A, Lichtenstein, AH, Folta, SC, Economos, CD, Jacques, PF, Livingston, KA, McKeown, NM
Nutrients. 2019;11(3)
-
-
-
Free full text
Plain language summary
Knowledge of plant-based diets is important for clinicians to be able to engage with patients about the health benefits and potential concerns. To date, the nutrient composition and nutrient adequacy of these diets has not been thoroughly assessed. The aim of this study was to estimate theoretical food and nutrient levels of whole-food plant-based (WFPB) and vegan diets and compare these levels to the US dietary recommendations. Self-identified vegan and WFPB diet followers reported their most frequently used books and websites for nutritional information and recipes. Using these sources, 30 days of theoretical meal plans were created, and this data was compared to recommendations from a MyPlate meal plan. This data was analysed to measure adherence to the 2015 Dietary Guidelines for Americans. This analysis showed the theoretical nutrient intake from a WFPB diet deviate significantly from MyPlate recommendations. The WFPB diet offered improved quality compared to the typical US diet, providing more nutrient-dense foods with less refined grains and added sugars. While WFPB diets are of higher quality in general, they risk deficiencies of vitamins B12 and D and calcium without adequate supplementation. Based on this analysis, the authors encourage patients to consider a plant-based dietary pattern with attention given to consuming calcium-rich foods, iodised salt, and using supplements for vitamins B12 and D. The authors comment that future research should examine the actual dietary intakes of these groups, rather than the theoretical, to assess actual nutrient intake and adherence to diet.
Abstract
Public interest in popular diets is increasing, in particular whole-food plant-based (WFPB) and vegan diets. Whether these diets, as theoretically implemented, meet current food-based and nutrient-based recommendations has not been evaluated in detail. Self-identified WFPB and vegan diet followers in the Adhering to Dietary Approaches for Personal Taste (ADAPT) Feasibility Survey reported their most frequently used sources of information on nutrition and cooking. Thirty representative days of meal plans were created for each diet. Weighted mean food group and nutrient levels were calculated using the Nutrition Data System for Research (NDSR) and data were compared to DRIs and/or USDA Dietary Guidelines/MyPlate meal plan recommendations. The calculated HEI-2015 scores were 88 out of 100 for both WFPB and vegan meal plans. Because of similar nutrient composition, only WFPB results are presented. In comparison to MyPlate, WFPB meal plans provide more total vegetables (180%), green leafy vegetables (238%), legumes (460%), whole fruit (100%), whole grains (132%), and less refined grains (-74%). Fiber level exceeds the adequate intakes (AI) across all age groups. WFPB meal plans failed to meet the Recommended Dietary Allowances (RDA)s for vitamin B12 and D without supplementation, as well as the RDA for calcium for women aged 51⁻70. Individuals who adhere to WFBP meal plans would have higher overall dietary quality as defined by the HEI-2015 score as compared to typical US intakes with the exceptions of calcium for older women and vitamins B12 and D without supplementation. Future research should compare actual self-reported dietary intakes to theoretical targets.
-
8.
Sex and menopausal status influence human dietary requirements for the nutrient choline.
Fischer, LM, daCosta, KA, Kwock, L, Stewart, PW, Lu, TS, Stabler, SP, Allen, RH, Zeisel, SH
The American journal of clinical nutrition. 2007;85(5):1275-85
-
-
-
Free full text
-
Plain language summary
Choline is used to form cell membranes, and it is a precursor for the neurotransmitter acetylcholine. Other than from the diet, choline can also be derived from the de novo biosynthesis of phosphatidylcholine. The current Adequate Intake for choline is considered sufficient to prevent deficiency, however an Estimated Average Requirement cannot be generated due to lack of availability of adequate human data. The aim of this study was to evaluate the dietary choline requirement in healthy men and women (pre- and postmenopausal), and to identify the clinical and metabolic sequelae of choline deficiency. Fifty-seven adult participants (26 healthy men, 16 premenopausal women and 15 postmenopausal women) were recruited for the study. A randomised double-blind protocol was followed to assign participants in one of the 2 arms; folate only (100 DFE) vs a dietary supplement of 400μg folic acid/d (768 DFE). Results show that independent of folate status, most men and postmenopausal women developed liver or muscle dysfunction when fed a low-choline diet, whereas premenopausal women were more resistant to developing such organ dysfunction. AP activity increased in all subjects in response to the low-choline diet regardless of whether they manifested organ dysfunction. Liver and muscle dysfunction occurred in response to a low-choline diet in both men and women. The current AI for choline was not be sufficient for some of the participants who became depleted despite this level of intake.
Abstract
BACKGROUND Although humans require dietary choline for methyl donation, membrane function, and neurotransmission, choline can also be derived from the de novo synthesis of phosphatidylcholine, which is up-regulated by estrogen. A recommended Adequate Intake (AI) exists for choline; however, an Estimated Average Requirement has not been set because of a lack of sufficient human data. OBJECTIVE The objective of the study was to evaluate the dietary requirements for choline in healthy men and women and to investigate the clinical sequelae of choline deficiency. DESIGN Fifty-seven adult subjects (26 men, 16 premenopausal women, 15 postmenopausal women) were fed a diet containing 550 mg choline x 70 kg(-1) x d(-1) for 10 d followed by <50 mg choline x 70 kg(-1) x d(-1) with or without a folic acid supplement (400 microg/d per randomization) for up to 42 d. Subjects who developed organ dysfunction during this diet had normal organ function restored after incremental amounts of choline were added back to the diet. Blood and urine were monitored for signs of toxicity and metabolite concentrations, and liver fat was assessed by using magnetic resonance imaging. RESULTS When deprived of dietary choline, 77% of men and 80% of postmenopausal women developed fatty liver or muscle damage, whereas only 44% of premenopausal women developed such signs of organ dysfunction. Moreover, 6 men developed these signs while consuming 550 mg choline x 70 kg(-1) x d(-1), the AI for choline. Folic acid supplementation did not alter the subjects' response. CONCLUSION Subject characteristics (eg, menopausal status) modulated the dietary requirement for choline, and a daily intake at the current AI was not sufficient to prevent organ dysfunction in 19 of the subjects.
