These therapies show efficacy in treating common cancer-related side effects, including nausea and vomiting, pain, fatigue, anxiety, depressive symptoms and improving overall quality of life. Some also have effects on biomarkers such as immune function and stress hormones. Overall studies lack large sample sizes and active comparison groups. Common issues around clearly defining treatments including standardizing treatment components, dose, intensity, duration and training of providers make generalization across studies difficult. MBTs in cancer care show great promise and evidence of efficacy for treating many common symptoms. Future studies should investigate more diverse cancer populations using standardized treatment protocols and directly compare various MBTs to one another.

There is a high prevalence of hyperhomocysteinemia that has been linked to high cardiovascular risk in obese individuals and could be attributed to poor nutritional status of folate and vitamin B12. We sought to examine the association between blood homocysteine (Hcy) folate, and vitamin B12 levels and vascular dysfunction in morbidly obese adults using novel ex vivo flow-induced dilation (FID) measurements of isolated adipose tissue arterioles. Brachial artery flow-mediated dilation (FMD) was also measured. Subcutaneous and visceral adipose tissue biopsies were obtained from morbidly obese individuals and non-obese controls. Resistance arterioles were isolated in which FID, acetylcholine-induced dilation (AChID), and nitric oxide (NO) production were measured in the absence or presence of the NO synthase inhibitor, L-NAME, Hcy, or the superoxide dismutase mimetic, TEMPOL. Our results demonstrated that plasma Hcy concentrations were significantly higher, while folate, vitamin B12, and NO were significantly lower in obese subjects compared to controls. Hcy concentrations correlated positively with BMI, fat %, and insulin levels but not with folate or vitamin B12. Brachial and arteriolar vasodilation were lower in obese subjects, positively correlated with folate and vitamin B12, and inversely correlated with Hcy. Arteriolar NO measurements and sensitivity to L-NAME were lower in obese subjects compared to controls. Finally, Hcy incubation reduced arteriolar FID and NO sensitivity, an effect that was abolished by TEMPOL. In conclusion, these data suggest that high concentrations of plasma Hcy and low concentrations of folate and vitamin B12 could be independent predictors of vascular dysfunction in morbidly obese individuals.

We thank the editor and the reviewers for their thoughtful review of our manuscript and for the opportunity to improve and resubmit. The detailed comments the authors received are indeed beneficial and improve the quality of our data presentation and interpretation. We have responded to the reviewers' comments/critiques below and have incorporated the recommended changes in the manuscript. Major concernsComment # 1: Do you have information on dietary preferences in your sample? Are there omnivores, vegetarian or vegans? This is important due to the potential use of vitamin supplements with vitamin B12. The authors did not discuss the differences in folate and vitamin B12 between controls and subjects with obesity, and how this is related with the observed methylation patterns… this should be addressed due to its one of the strengths of this study. Response to comment # 1:We agree with the reviewer and we obtained questionnaires about supplementations however, most subjects were not able to recall taking supplements that specifically rich in folate or vitamin B12. Accordingly, we decided to measure actual concentrations of folate and B12 in plasma. Also, we do not have specific information about dietary preferences of our subjects but realizing the importance of this information, we will start to implement this questionnaire in our future studies. We also agree that the part about vitamin B12 and folate in obese and non-obese subjects and the relation to methylation was missing in the discussion. Per your recommendation, we added a new paragraph that discusses this part (lines 341-360).Comment # 2: The data in table 2 was analyzed by sex? Considering that HDL-C cut-off is different among men and women…Response to comment # 2: Results for HDL-C did not show significant differences between males and females within each group (obese and non-obese). When compared, the p value was higher than 0.7 in both groups. Comment # 3:The authors show interesting data in Table 2, where HOMA index and FPI is higher in obese subjects in comparison to controls, however, FPG and HbA1c are not different among groups as expected. Please discuss about these result.Response to comment # 3: Insulin can be higher in obese individuals which results in higher HOMA-IR at earlier stages of insulin resistance before the conditions mature to full-blown diabetes where glucose metabolism is actually compromised and manifested as high blood glucose. We believe that some of subjects in the obese group are at early stages of insulin resistance but since they are young (mid 30s in average), a complete picture of diabetes might not have been developed yet. A statement that explain this was added to the discussion (lines 260-263)Comment # 4: Alcohol consumption was measured by a questionnaire, is this validated? This information is not described in methods, fix this issue. In table 2 the data appears as "alcohol drinkers %", however, in the discussion, the authors mentioned that they have classified into none, mild, moderate and heavy drinking, but this...

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Background. Cancer survivors use complementary therapies (CTs) for a variety of reasons; however, with interest and use reportedly on the rise and a widening range of products and practices available, there is a need to establish trends in and drivers of interest. We aimed to determine (1) frequencies of use, level of interest, and barriers for 30 specific CTs and (2) whether physical symptoms, perceived stress (PS), or spiritual well-being were related to interest levels. Method. A total of 212 cancer outpatients were surveyed at the Tom Baker Cancer Centre in Calgary, Canada. Results. Overall, up to 75% of survivors already used some form of CTs since their diagnosis. The most highly used were the following: vitamins B12 and D, multivitamins, calcium, and breathing and relaxation exercises. Those who had not used CTs indicated highest interest in massage, vitamin B12, breathing and relaxation, mindfulness-based stress reduction, and antioxidants. The most frequently reported barriers for all CTs were not knowing enough about what a therapy was and not having enough evidence on whether it worked. High PS predicted higher interest for all CTs, but spirituality was not significantly related to any. Physical symptoms, anxiety, and depression were significant predictors of interest for some CTs. Conclusion. These findings provide a blueprint for future clinical efficacy trials and highlight the need for clinical practice guidelines.