Dietary strategies for chemotherapy-induced nausea and vomiting: A systematic review.

BACKGROUND & AIMS: Chemotherapy-induced nausea and vomiting (CINV) is one of the most distressing cancer treatment side effects, affecting 20-70% of patients despite routine antiemetic prescription. Although dietary modifications are routinely recommended in clinical practice, there is lack of data synthesis to determine which dietary strategies for managing CINV are supported by quality evidence. This systematic review was conducted to examine the effect of dietary strategies on incidence and severity of CINV in adults compared with no intervention, usual care, or alternative strategies. METHODS: Five electronic databases were searched from inception to 15th July 2021 for original research studies of interventional or observational design assessing dietary strategies for CINV. The quality of evidence was appraised, data were synthesized narratively, and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment of the certainty of the evidence was applied. RESULTS: Twenty-one studies were included, 10 (48%) interventional studies and 11 (52%) observational studies. Most interventional and observational studies had a high or neutral risk of bias (70% and 72%, respectively). Of the interventions studied, strongest evidence with highest certainty was found for the very large positive effect of CINV-specific education and support with a personalized meal plan from a dietician, implemented in person or in writing, for reducing the severity of nausea and overall CINV (effect size: very large; GRADE: high). A statistically significant very large positive effect of ginger tea consumption was also found on overall CINV severity; however, certainty in this effect was very low. Although confidence in the findings from observational studies was very low to low, a statistically significant positive association was also found between a moderate intake of alcohol and incidence of nausea, vomiting, or overall CINV as well as nausea severity; the Mediterranean diet and nausea incidence and severity; and adequate intake of energy, protein, fat, or carbohydrate and nausea or vomiting incidence. CONCLUSION: Improved CINV was associated with CINV-specific nutrition education and support from health professionals. Non-restrictive dietary patterns that include adequate energy and macronutrient intakes, particularly protein, and include ginger, and Mediterranean diet concepts may benefit CINV; however, the confidence in the body of evidence to inform these conclusions is mostly very low to moderate. Future rigorous trials with adequate sample sizes, clearly defined dietary strategies, and valid outcome measures are warranted prior to dietary strategies being routinely prescribed alongside antiemetic regimens.

Identification of four novel QTL linked to the metabolic syndrome in the Berlin Fat Mouse.

BACKGROUND: The Berlin Fat Mouse Inbred line (BFMI) is a model for obesity and the metabolic syndrome. This study aimed to identify genetic variants associated with impaired glucose metabolism using the obese lines BFMI861-S1 and BFMI861-S2, which are genetically closely related, but differ in several traits. BFMI861-S1 is insulin resistant and stores ectopic fat in the liver, whereas BFMI861-S2 is insulin sensitive. METHODS: In generation 10, 397 males of an advanced intercross line (AIL) BFMI861-S1 × BFMI861-S2 were challenged with a high-fat, high-carbohydrate diet and phenotyped over 25 weeks. QTL-analysis was performed after selective genotyping of 200 mice using the GigaMUGA Genotyping Array. Additional 197 males were genotyped for 7 top SNPs in QTL regions. For the prioritization of positional candidate genes whole genome sequencing and gene expression data of the parental lines were used. RESULTS: Overlapping QTL for gonadal adipose tissue weight and blood glucose concentration were detected on chromosome (Chr) 3 (95.8-100.1 Mb), and for gonadal adipose tissue weight, liver weight, and blood glucose concentration on Chr 17 (9.5-26.1 Mb). Causal modeling suggested for Chr 3-QTL direct effects on adipose tissue weight, but indirect effects on blood glucose concentration. Direct effects on adipose tissue weight, liver weight, and blood glucose concentration were suggested for Chr 17-QTL. Prioritized positional candidate genes for the identified QTL were Notch2 and Fmo5 (Chr 3) and Plg and Acat2 (Chr 17). Two additional QTL were detected for gonadal adipose tissue weight on Chr 15 (67.9-74.6 Mb) and for body weight on Chr 16 (3.9-21.4 Mb). CONCLUSIONS: QTL mapping together with a detailed prioritization approach allowed us to identify candidate genes associated with traits of the metabolic syndrome. In addition, we provided evidence for direct and indirect genetic effects on blood glucose concentration in the insulin-resistant mouse line BFMI861-S1.

Both high fat and high carbohydrate diets impair vagus nerve signaling of satiety.

Obesity remains prevalent in the US. One potential treatment is vagus nerve stimulation (VNS), which activates the sensory afferents innervating the stomach that convey stomach volume and establish satiety. However, current VNS approaches and stimulus optimization could benefit from additional understanding of the underlying neural response to stomach distension. In this study, obesity-prone Sprague Dawley rats consumed a standard, high-carbohydrate, or high-fat diet for several months, leading to diet-induced obesity in the latter two groups. Under anesthesia, the neural activity in the vagus nerve was recorded with a penetrating microelectrode array while the stomach was distended with an implanted balloon. Vagal tone during distension was compared to baseline tone prior to distension. Responses were strongly correlated with stomach distension, but the sensitivity to distension was significantly lower in animals that had been fed the nonstandard diets. The results indicate that both high fat and high carbohydrate diets impair vagus activity.

Improvement of Obesity and Dyslipidemic Activity of Amomum tsao-ko in C57BL/6 Mice Fed a High-Carbohydrate Diet.

Amomum tsao-ko Crevost et Lemaire (Zingiberaceae) is a medicinal herb found in Southeast Asia that is used for the treatment of malaria, abdominal pain, dyspepsia, etc. The aim of this study was to investigate the effect of an ethanol extract of Amomum tsao-ko (EAT) on obesity and hyperlipidemia in C57BL/6 mice fed a high-carbohydrate diet (HCD). First, the mice were divided into five groups (n = 6/group) as follows: normal diet, HCD, and HCD+EAT (100, 200, and 400 mg/kg/day), which were orally administered with EAT daily for 84 days. Using microcomputed tomography (micro-CT) analysis, we found that EAT inhibited not only body-weight gain, but also visceral fat and subcutaneous fat accumulation. Histological analysis confirmed that EAT decreased the size of fat tissues. EAT consistently improved various indices, including plasma levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein, high-density lipoprotein, atherogenic index, and cardiac risk factors, which are related to dyslipidemia-a major risk factor for heart disease. The contents of TC and TG, as well as the lipid droplets of HCD-induced hepatic accumulation in the liver tissue, were suppressed by EAT. Taken together, these findings suggest the possibility of developing EAT as a therapeutic agent for improving HCD-induced obesity and hyperlipidemia.

Different elemental infant formulas show equivalent phosphorus and calcium bioavailability in healthy volunteers.

Retrospective chart reviews have reported hypophosphatemia associated with elemental formula use in infants and children with systemic disease involving multiple diagnoses. The present study aims to evaluate the bioavailability of phosphorus from 2 commercial elemental formulas and to test our hypothesis of bioequivalence of the 2 products in healthy volunteers receiving gastric acid-suppressive medication. A single-center, double-blind, randomized, cross-over study was conducted in healthy volunteers with esomeprazole-induced hypochlorhydria. After a standardized low phosphorus meal followed by overnight fasting, subjects consumed 1 gram of phosphorus in a single oral dose of 1217 kcal of Product A (Neocate) or Product B (Elecare). The alternate product was given following a 1-week washout period. Blood and urine were collected at baseline and different time-points for up to 6 hours after product consumption. Area-under-the-curve (AUC) and peak values (Cpeak) for serum phosphate and calcium and urinary creatinine-corrected phosphate and calcium were assessed for bioequivalence of Products A and B. Results show that the geometric mean ratio (GMR) and 90% CI for serum phosphate were 1.041 (0.998-1.086) and 1.020 (0.963-1.080) for AUC0-360 and Cpeak, respectively, meeting the predetermined criteria for bioequivalence. Urinary creatinine-corrected phosphate followed a similar pattern after intake of Product A and B, but did not reach bioequivalence criteria (GMR: AUC70-370 = 1.105 (0.918-1.330); Cpeak = 1.182 (1.040-1.343)). Serum calcium concentrations (GMR: AUC0-360 = 1.002 (0.996-1.009); Cpeak = 0.991 (0.983-0.999)) and urinary creatinine-corrected calcium excretion (GMR: AUC70-370 = 1.117 (1.023-1.219); Cpeak = 1.157 (1.073-1.247)) demonstrated bioequivalence of the products. In conclusion, both elemental infant formulas showed equivalent serum phosphorus and calcium bioavailability in healthy volunteers even if combined with treatment with acid-suppressive medication.

The History of Carbohydrates in Type I Allergy.

Although first described decades ago, the relevance of carbohydrate specific antibodies as mediators of type I allergy had not been recognized until recently. Previously, allergen specific IgE antibodies binding to carbohydrate epitopes were considered to demonstrate a clinically irrelevant cross-reactivity. However, this changed following the discovery of type I allergies specifically mediated by oligosaccharide structures. Especially the emerging understanding of red meat allergy characterized by IgE directed to the oligosaccharide alpha-gal showed that carbohydrate-mediated reactions can result in life threatening systemic anaphylaxis which in contrast to former assumptions proves a high clinical relevance of some carbohydrate allergens. Within the scope of this review article, we illustrate the historical development of carbohydrate-allergen-research, reaching from only diagnostically relevant crossreactive-carbohydrate-determinants to clinically important antigens mediating type I allergy. Focusing on clinical and immunological features of the alpha-gal syndrome, we highlight the discovery of oligosaccharides as potentially highly immunogenic antigens and mediators of type I allergy, report what is known about the route of sensitization and the immunological mechanisms involved in sensitization and elicitation phase of allergic responses as well as currently available diagnostic and therapeutic tools. Finally, we briefly report on carbohydrates being involved in type I allergies different from alpha-gal.

Nutritional adequacy of very low- and high-carbohydrate, low saturated fat diets in adults with type 2 diabetes: A secondary analysis of a 2-year randomised controlled trial.

BACKGROUND: Growing evidence supports use of very low-carbohydrate (LC) diets for glycaemic control in type 2 diabetes. However, limited data on the micronutrient adequacy of LC diets exist. OBJECTIVE: This study compared the long-term effects of a very low-carbohydrate, high unsaturated/low saturated fat (LC) diet to a high-carbohydrate, low-fat (HC) diet on micronutrient biomarkers in adults with obesity and type 2 diabetes. METHODS: 115 adults with type 2 diabetes (mean[SD]; BMI:34.6[4.3]kg/m2, age:58[7]yrs, HbA1c:7.3[1.1]%, 56[12]mmol/mol) were randomized to one of two planned, nutritionally-replete, energy-matched, hypocaloric diets (500-1000 kcal/day deficit): (1) LC:14% energy carbohydrate, 28%protein, 58%fat[<10% saturated fat]) or (2) HC:53%carbohydrate, 17%protein, 30%fat [<10%saturated fat]) for 2 years. Nutritional biomarkers- folate, ß-carotene, vitamin B12, D, E, copper, zinc, selenium, calcium, magnesium, sodium, potassium, iron, ferritin, transferrin and transferrin saturation were measured in fasting blood at baseline, 24, 52 and 104 weeks. RESULTS: 61 participants completed the study with similar dropouts in each group (P = 0.40). For all biomarkers assessed, there were no differential response between groups overtime (P ≥ 0.17 time × diet interaction). Mean vitamin and mineral levels remained within normal (laboratory-specific) reference ranges without any reported cases of clinical deficiencies. CONCLUSION: In free-living individuals with type 2 diabetes, nutrition biomarkers within normal ranges at baseline did not change significantly after 2 years on a prescribed LC or HC diet. These results demonstrate the feasibility of delivering a nutritionally replete LC diet and the importance of considering nutritional factors in planning LC diets that have strong public health relevance to the dietary management of type 2 diabetes. TRIAL REGISTRATION: http://www.anzctr.org.au/, ANZCTR No. ACTRN12612000369820.

Ketogenic diet: a pharmaceutical guide for the management of drug therapy in the pediatric population.

For a ketogenic diet to be effective, strict control of carbohydrate intake is paramount. Factors such as medications may upset this delicate balance. The aim of this commentary is to provide physicians who are treating patients with a ketogenic diet, with a step-by-step guide. A list of unsuitable excipients was established. A flowchart with the title "Can this drug be prescribed to a patient following a ketogenic diet?" was then drafted. The first step is to determine the international nonproprietary name, dosage, form and composition. The amount of unsuitable excipients is calculated. Suitable alternatives may be discussed with the pharmacist. As a last resort, the ketogenic diet itself may need to be adapted. The answers provided are included in a database. Determining the amount of unsuitable excipients is a complex task requiring pharmaceutical expertise. Our flowchart can be used in order to provide a clear pathway for answering such questions.

Impact of oral carbohydrate consumption prior to cesarean delivery on preoperative well-being: a randomized interventional study.

PURPOSE: Oral carbohydrate consumption before surgery improves insulin sensitivity, cardiac output and well-being, and shortens hospital stays without adverse effects. No work has compared higher-dose carbohydrate beverages made for preoperative consumption to common, commercial oral rehydration solutions with lower carbohydrate concentrations. METHODS: We recruited low-risk women undergoing scheduled cesarean deliveries with planned spinal anesthesia. Participants were randomized to one of three groups: those who consumed Clearfast® beverage, those who consumed Gatorade Thirst Quencher® beverage, or fasting control. Participants in the two beverage groups received 710 mL of the appropriate beverage the night before surgery and 355 mL 2 h before surgery. Participants in the control group fasted after midnight the night before surgery. Two hours before surgery, we recorded baseline patient well-being using visual analogue scales, followed by beverage consumption for subjects in the beverage groups. One hour later, we repeated the same assessment. Additional recorded measures included cord blood glucose level, intraoperative variables, breastfeeding success, and a quality of recovery assessment administered 1 day after surgery. RESULTS: Forty-seven patients were recruited: 15 received Clearfast®, 17 received Gatorade Thirst Quencher®, and 15 patients fasted after midnight. Group differences in change in patient well-being using visual analog scales were analyzed using linear regression. Both beverage-consuming groups showed significant improvements in patient well-being using visual analog scales while fasted patients showed no change. CONCLUSION: Either a common oral rehydration beverage or a higher-dose carbohydrate beverage consumed preoperatively resulted in superior well-being compared to fasting. No differences in other outcomes were noted. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov with clinical trial registration number: NCT02684513.

Postprandial remodeling of high-density lipoprotein following high saturated fat and high carbohydrate meals.

BACKGROUND: Humans spend most of the time in the postprandial state, yet most knowledge about high-density lipoproteins (HDL) derives from the fasted state. HDL protein and lipid cargo mediate HDL's antiatherogenic effects, but whether these HDL constituents change in the postprandial state and are affected by dietary macronutrients remains unknown. OBJECTIVES: This study aimed to assess changes in HDL protein and lipid composition after the consumption of a high-carbohydrate or high saturated fat (HSF) meal. METHODS: We isolated HDL from plasma collected during a randomized, cross-over study of metabolically healthy subjects. Subjects consumed isocaloric meals consisting predominantly of either carbohydrate or fat. At baseline and at 3 and 6 hours postprandial, we quantified HDL protein and lipid composition by liquid chromatography-mass spectrometry. RESULTS: A total of 15 subjects were included (60% female, aged 34 ± 15 years, body mass index: 24.1 ± 2.7 kg/m2). Consumption of the HSF meal led to HDL enrichment in total lipid (P = .006), triglyceride (P = .02), and phospholipid (P = .008) content and a corresponding depletion in protein content. After the HSF meal, 16 of the 25 measured phosphatidylcholine species significantly increased in abundance (P values range from .027 to <.001), along with several sphingolipids including ceramides (P < .004), lactosylceramide (P = .023), and sphingomyelin-14 (P = .013). Enrichment in apolipoprotein A-I (P = .001) was the only significant change in HDL protein composition after the HSF meal. The high-carbohydrate meal conferred only minimal changes in HDL composition. CONCLUSION: Meal macronutrient content acutely affects HDL composition in the postprandial state, with the HSF meal resulting in enrichment of HDL phospholipid content with possible consequences for HDL function.

Nutritional hypophosphatemic rickets secondary to Neocate® use.

Elemental formula is commonly used in children with feeding intolerance. We describe two, medically complex and feeding tube dependent, patients exclusively fed with Neocate® who subsequently developed hypophosphatemic rickets. Both patients had gross motor decline and pain with physical touch. They were found to have low serum phosphorus, normal calcium, and vitamin D studies, with elevated alkaline phosphatase suggestive of nutritional hypophosphatemia. Both courses were complicated by hypocalcemia following formula change and phosphorus supplementation, highlighting the need for careful management of phosphate repletion in affected individuals. Diligent serial electrolyte monitoring as well as attention to bone health is needed in conjunction with elemental nutrition. Formula change led to restoration of calcium and phosphorus homeostasis and radiographic improvement in these patients.

Elemental formula associated hypophosphataemic rickets.

OBJECTIVES: Hypophosphataemic rickets (HR) is usually secondary to renal phosphate wasting but may occur secondary to reduced intake or absorption of phosphate. We describe a series of cases of HR associated with the use of Neocate®, an amino-acid based formula (AAF). METHODS: A retrospective review of cases with HR associated with AAF use presenting to centres across the United Kingdom. RESULTS: 10 cases were identified, over a 9 month period, all associated with Neocate® use. The age at presentation was 5 months to 3 years. The majority (8/10) were born prematurely. Gastro oesophageal reflux disease (6/10) was the most frequent indication for AAF use. Radiologically apparent rickets was observed after a median of 8 months (range 3-15 months) of exclusive Neocate® feed. The majority (7/10) were diagnosed on the basis of incidental findings on radiographs: rickets (6/10) or fracture with osteopenia (5/10). All patients had typical biochemical features of HR with low serum phosphate, high alkaline phosphatase, normal serum calcium and 25 hydroxyvitamin D. However, in all cases the tubular reabsorption of phosphate (TRP) was ≥96%. Phosphate supplementation resulted in normalisation of serum phosphate within 1-16 weeks, and levels remained normal only after Neocate® cessation. In patients with sufficient follow up duration (4/10), normalisation of phosphate and radiological healing of rickets was noted after 6 months (range: 6-8 months) following discontinuation of Neocate®. CONCLUSION: The presence of a normal TRP and resolution of hypophosphataemia and rickets following discontinuation of Neocate® indicates this is a reversible cause likely mediated by poor phosphate absorption. Close biochemical surveillance is recommended for children on Neocate®, especially in those with gastrointestinal co-morbidities, with consideration of a change in feed or phosphate supplementation in affected children.

Hepatic steatosis risk is partly driven by increased de novo lipogenesis following carbohydrate consumption.

BACKGROUND: Diet is a major contributor to metabolic disease risk, but there is controversy as to whether increased incidences of diseases such as non-alcoholic fatty liver disease arise from consumption of saturated fats or free sugars. Here, we investigate whether a sub-set of triacylglycerols (TAGs) were associated with hepatic steatosis and whether they arise from de novo lipogenesis (DNL) from the consumption of carbohydrates. RESULTS: We conduct direct infusion mass spectrometry of lipids in plasma to study the association between specific TAGs and hepatic steatosis assessed by ultrasound and fatty liver index in volunteers from the UK-based Fenland Study and evaluate clustering of TAGs in the National Survey of Health and Development UK cohort. We find that TAGs containing saturated and monounsaturated fatty acids with 16-18 carbons are specifically associated with hepatic steatosis. These TAGs are additionally associated with higher consumption of carbohydrate and saturated fat, hepatic steatosis, and variations in the gene for protein phosphatase 1, regulatory subunit 3b (PPP1R3B), which in part regulates glycogen synthesis. DNL is measured in hyperphagic ob/ob mice, mice on a western diet (high in fat and free sugar) and in healthy humans using stable isotope techniques following high carbohydrate meals, demonstrating the rate of DNL correlates with increased synthesis of this cluster of TAGs. Furthermore, these TAGs are increased in plasma from patients with biopsy-confirmed steatosis. CONCLUSION: A subset of TAGs is associated with hepatic steatosis, even when correcting for common confounding factors. We suggest that hepatic steatosis risk in western populations is in part driven by increased DNL following carbohydrate rich meals in addition to the consumption of saturated fat.

Caramel color safety - An update.

Caramel color has been used in foods and beverages for over 150 years and is globally regulated as a color additive. The four distinct classes of caramel color (Plain Caramel, Sulfite Caramel, Ammonia Caramel, and Sulfite Ammonia Caramel) are well characterized and each have specifications that take into account processing variables including reactants that can give rise to low molecular weight constituents (e.g., 4-MeI and THI) that may have toxicological significance for evaluating safety. Extensive safety testing has been conducted with the different classes of caramel color and its constituents, including toxicokinetics, genotoxicity, subchronic toxicity, carcinogenicity, and reproductive/developmental toxicity studies. In addition, data is available on uses and use levels that have been used to estimate intakes of caramel colors and their constituents. No Observable Adverse Effect Levels (NOAEL) have been identified for all classes and Acceptable Daily Intakes have been established to ensure safety of use. Available studies support a conclusion that caramel colors are not genotoxic or carcinogenic, and exposure estimates indicate that intake of caramel colors and constituents do not pose undue safety risks. This update summarizes available relevant safety studies and authoritative reviews on caramel colors and its toxicologically important constituents, 4-MeI and THI.

Glycemic index, glycemic load and carbohydrate intake in association with risk of renal cell carcinoma.

Carbohydrate intake affects postprandial glucose levels and insulin response, which plays a role in carcinogenesis. The relationship between carbohydrate intake, dietary glycemic index (GI) and glycemic load (GL), and risk of renal cell carcinoma (RCC) remains unclear. We conducted a case-control study including 854 patients with newly diagnosed RCC (cases) and 1255 healthy participants (controls) recruited since 2002. GI, GL and carbohydrate intake were obtained via a validated food frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression, adjusting for potential confounders. We found that higher GI was significantly associated with RCC risk with an OR of 1.32 (95% CI, 0.99-1.74; Ptrend = 0.026) (the highest versus the lowest quartiles). We also observed an inverse association between fiber intake and RCC risk with OR of 0.70 (95% CI = 0.50-0.99) as well as between starch intake and risk of RCC with OR of 0.65 (95% CI = 0.49-0.87). Individuals with a high-GI diet and hypertension or high body mass index (BMI) had a 2.7 times (OR = 2.67, 95% CI = 1.96-3.64) and two times (OR = 1.95, 95% CI = 1.29-2.92) higher RCC risk, respectively, than those without these factors. Our findings suggest that a high-GI diet is associated with an increased risk of RCC, whereas increased fiber and starch intakes appear to be associated with a decreased risk of RCC. We found that reducing GI levels and increasing fiber intake could be a dietary strategy to decrease RCC risk, especially for individuals with hypertension or high BMI.

Carbohydrate fatty acid monosulphate esters are safe and effective adjuvants for humoral responses.

Carbohydrate fatty acid sulphate esters (CFASEs) formulated in a squalane-in-water emulsion are effective adjuvants for humoral responses to a wide range of antigens in various animal species but rise in body temperature and local reactions albeit mild or minimal hampers application in humans. In rabbits, body temperature increased 1°C one day after intramuscular (IM) injection, which returned to normal during the next day. The effect increased with increasing dose of CFASE but not with the number of injections (up to 5). Antigen enhanced the rise in body temperature after booster immunization (P<0.01) but not after priming. Synthetic CFASEs are mixtures of derivatives containing no sulphate, one or multiple sulphate groups and the monosulphate derivatives (CMS) were isolated, incorporated in a squalane in-water emulsion and investigated. In contrast to CFASE, CMS adjuvant did not generate rise in body temperature or local reactions in rabbits immunized with a purified, recombinant malaria chimeric antigen R0.10C. In comparison to alum, CMS adjuvant revealed approximately 30-fold higher antibody titres after the first and >100-fold after the second immunization. In ferrets immunized with 7.5µg of inactivated influenza virus A/H7N9, CMS adjuvant gave 100-fold increase in HAI antibody titres after the first and 25-fold after the second immunisation, which were 10-20-fold higher than with the MF59-like AddaVax adjuvant. In both models, a single immunisation with CMS adjuvant revealed similar or higher titres than two immunisations with either benchmark, without detectable systemic and local adverse effects. Despite striking chemical similarities with monophospholipid A (MPL), CMS adjuvant did not activate human TLR4 expressed on HEK cells. We concluded that the synthetic CMS adjuvant is a promising candidate for poor immunogens and single-shot vaccines and that rise in body temperature, local reactions or activation of TLR4 is not a pre-requisite for high adjuvanticity.

Psychologically Informed Implementations of Sugary-Drink Portion Limits.

In 2012, the New York City Board of Health prohibited restaurants from selling sugary drinks in containers that would hold more than 16 oz. Although a state court ruled that the Board of Health did not have the authority to implement such a policy, it remains a legally viable option for governments and a voluntary option for restaurants. However, there is very limited empirical data on how such a policy might affect the purchasing and consumption of sugary drinks. We report four well-powered, incentive-compatible experiments in which we evaluated two possible ways that restaurants might comply with such a policy: bundling (i.e., dividing the contents of oversized cups into two regulation-size cups) and providing free refills (i.e., offering a regulation-size cup with unlimited refills). Bundling caused people to buy less soda. Free refills increased consumption, especially when a waiter served the refills. This perverse effect was reduced in self-service contexts that required walking just a few steps to get a refill.