Does Eating Too Much Sugar Cause Cancer?

The association between intake of total and added sugar and cancer risk was examined in a prospective cohort study of 101,279 French adults (median age, 40.8 years) participating in the NutriNet-Sante prospective cohort study. During a median follow-up period of 5.9 years, after adjustment for known risk factors (sociodemographic, anthropometric, lifestyle, medical history, and nutritional factors), total sugar intake was positively associated with overall cancer risk. The hazard ratio (HR) comparing the highest and lowest quartiles of intake was 1.17 (p for trend = 0.02). For breast cancer, comparing the highest and lowest quartiles, the HR was 1.51 (p for trend = 0.0007).

Comment: In this study, higher sugar intake was associated with an increased risk of total cancers and breast cancer. Although observational studies cannot prove causation, the possibility that eating too much sugar can promote cancer is biologically plausible. High sugar intake can increase obesity, insulin resistance, inflammation, and oxidative stress; and each of these factors is associated with an increased risk of developing various types of cancer. In addition, refined sugar contains no vitamins and minerals and, therefore, dilutes the diet with respect to potential anti-cancer nutrients such as vitamin C, zinc, and selenium.

Debras C, et al. Total and added sugar intakes, sugar types, and cancer risk: results from the prospective NutriNet-Sante cohort. Am J Clin Nutr. 2020;112:1267-1279.

Can Vitamin D Prevent Cancer?

In the Vitamin D and Omega-3 Trial (VITAL), 25,871 men and women (mean age, 67.1 years) in the United States who did not have cardiovascular disease or cancer at baseline were randomly assigned to receive, in double-blind fashion, 2,000 IU per day of vitamin D, 1 g per day of fish oil (Omacor; providing daily 460 mg of eicosapentaenoic acid and 380 mg of docosahexaenoic acid), both treatments, or placebo (olive oil) for a median duration of 5.3 years. As previously reported, no significant differences in cancer incidence were seen in any of the groups. However, in this new secondary analysis, the proportion of participants who developed advanced cancers (metastatic or fatal) was significantly lower in the vitamin D group than in the placebo group (1.7% vs. 2.1%; hazard ratio [HR] = 0.83; p = 0.04). When stratified by body mass index (BMI), the reduction in risk of advanced cancers associated with vitamin D treatment was significant for those with a normal BMI (< 25 kg/m²; HR = 0.62; 95% confidence interval [CI], 0.45-0.86). In contrast, there was no significant effect of vitamin D in participants who were overweight or obese (BMI of 25 to < 30 kg/m²: HR = 0.89; 95% CI, 0.68-1.17; BMI of 30 kg/m² or higher: HR = 1.05; 95% CI, 0.74-1.49) (p for interaction by BMI = 0.03).

Comment: These findings suggest that vitamin D supplementation can decrease the incidence of advanced cancers in normal-weight individuals, but not in people who are overweight or obese. Since vitamin D had no significant effect on the incidence of cancer, it would seem that vitamin D supplementation prevented the progression of some cancers to an advanced stage. Two possible explanations come to mind regarding why vitamin D was not beneficial for overweight and obese people. First, vitamin D is readily taken up by adipose tissue (of which overweight and obese people have more) and therefore might be less available to exert its various biochemical effects in the rest of the body. Second, obesity is associated with many potentially cancer-promoting biochemical abnormalities such as chronic inflammation, increased oxidative stress, and insulin resistance. Some of these factors might overshadow any potential benefit of vitamin D.

Chandler PD, et al. Effect of vitamin D3 supplements on development of advanced cancer: a secondary analysis of the VITAL randomized clinical trial. JAMA Netw Open. 2020;3:e2025850.

Is Testosterone Therapy Safe for Men with a History of Prostate Cancer?

The authors of this study followed 850 patients who underwent radical prostatectomy for prostate cancer, performed by a single surgeon from 2009 to 2018. One hundred fifty-two patients (18.2%) received postoperative testosterone replacement therapy (TRT) because they had a low preoperative calculated free-testosterone level (calculated from serum testosterone and sex hormone-binding globulin levels) and a delayed postoperative recovery of sexual function. These patients were compared with 419 control patients matched by Gleason Grade Group and stage. Biochemical recurrence was defined as two consecutive prostate-specific antigen (PSA) values greater than 0.2 ng/ml. During a median follow-up period of 3.5 years, biochemical recurrence occurred in 7.2% of patients receiving TRT and 12.6% of patients in the control group (p = 0.07). In adjusted time-to-event analysis, TRT was an independent predictor of recurrence-free survival. After accounting for Gleason Grade Group, pathological stage, preoperative PSA level, and calculated free-testosterone level, patients receiving TRT were 54% less likely to have a recurrence. In men who had a recurrence, TRT delayed the time to recurrence by an average of 1.5 years. There were no identifiable health complications associated with TRT.

Comment: Androgens promote the development and progression of prostate cancer in experimental models. Concern has therefore been raised that TRT is unsafe for patients with a history of prostate cancer. However, there is no clear evidence that testosterone promotes the development or progression of prostate cancer in humans. The results of the present study are consistent with previous studies, which found no increase in disease progression in prostate cancer patients receiving TRT.

Ahlering TE, et al. Testosterone replacement therapy reduces biochemical recurrence after radical prostatectomy. BJU Int. 2020;126:91-96.

Can Whole Grains Prevent Colon Cancer?

The association between intake of whole grains, intake of fiber, and risk of colorectal cancer was examined in a prospective cohort study of 478,994 US adults (aged 50-71 years) participating in the NIH-AARP Diet and Health Study. Diet was assessed using a food-frequency questionnaire at baseline in 1995-1996. During a follow-up period of 16 years, 10,200 cases of colorectal cancer were documented. After adjustment for potential confounding variables (including age, body mass index, physical activity, alcohol intake, smoking, intake of red and processed meat, and family history of cancer), there was an inverse association between intake of whole grains and colorectal cancer. The hazard ratio (HR) comparing the highest and lowest quintiles of intake was 0.84 (p for trend < 0.001). The HR for fiber intake (comparing extreme quintiles) was 0.96 (p for trend = 0.40), and for fiber from grains was 0.89 (p for trend < 0.001). There was no significant association between fiber intake from non-grain sources and colorectal cancer.

Comment: Dietary fiber may have certain actions that could decrease the risk of developing colon cancer. These include binding or diluting carcinogens in the intestinal tract, decreasing the conversion of bile acids to carcinogens, production of anticarcinogenic short chain fatty acids as a byproduct of fiber fermentation, and speeding intestinal transit (thereby decreasing the contact time between carcinogens and the bowel wall).^1,2 In addition to having a number of potential direct anticancer effects, the fiber components of some plants are the main dietary sources of lignans, a group of diphenolic compounds that have anticancer activity.³

In the present study, higher intake of whole grains and of fiber from grains (but not fiber from other sources) was associated with a lower incidence of colorectal cancer.

Hullings AG, et al. Whole grain and dietary fiber intake and risk of colorectal cancer in the NIH-AARP Diet and Health Study cohort. Am J Clin Nutr, 2020;112:603-612.

Zinc-L-Carnosine Prevents Chemotherapy Side Effect

Ninety-one patients with hematologic cancer who were scheduled for high-dose chemotherapy followed by hematopoietic stem cell transplantation (HSCT) were randomly assigned to a prevention group (in which zinc-L-carnosine lozenges were started before chemotherapy) or to a control group (in which the lozenges were started immediately after the onset of Grade 2 oral mucositis). Each lozenge contained 18.75 mg of zinc-L-carnosine, and one lozenge was dissolved in the mouth four times per day. Oral mucositis was evaluated daily from the start of chemotherapy until 35 days after transplantation. The incidence of Grade 2-or-higher oral mucositis was significantly lower in the prevention group than in the control group (22.0% vs. 44.7%; p = 0.025). Zinc-L-carnosine did not affect the outcome of HSCT.

Comment: L-Carnosine (beta-alanyl-L-histidine) occurs naturally in the body and has demonstrated multiple biochemical actions, including antioxidant and anti-inflammatory activity. In a previous study, oral zinc supplementation (not as lozenges) prevented chemotherapy-induced mucositis, but in another study zinc was ineffective. In the present study, zinc-L-carnosine lozenges prevented Grade 2-or-higher oral mucositis associated with high-dose chemotherapy, without influencing the outcome of the cancer treatment. Further research is needed to determine whether zinc-L-carnosine is more effective than zinc or L-carnosine alone.

Kitagawa J, et al. Polaprezinc for prevention of oral mucositis in patients receiving chemotherapy followed by hematopoietic stem cell transplantation: a multi-institutional randomized controlled trial. Int J Cancer. 2021;148:1462-1469.

Zinc-L-Carnosine Prevents Side Effects of Radiation Therapy

Forty patients with breast cancer who were undergoing radiation therapy were randomly assigned to receive 10 ml of a suspension of zinc-L-carnosine or placebo twice a day. According to a personal communication from one of the authors, each 10 ml of suspension contained 38 mg of zinc-L-carnosine. Treatment was started on day 1 of radiation therapy and was continued until radiation therapy was complete or until dysphagia developed, at which point steroid therapy was prescribed. The proportion of patients who developed grade 1 or 2 esophagitis (50% vs. 100%; p < 0.0001) and the proportion of patients who needed steroid treatment (15% vs. 85%; p < 0.0001) were significantly lower in the zinc-L-carnosine group than in the placebo group.

Comment: This study demonstrated that treatment with a zinc-L-carnosine suspension markedly decreased the incidence of radiation-induced esophagitis and decreased the need for steroid therapy in patients undergoing radiation therapy for breast cancer.

Saldi S, et al. Zinc-L-carnosine prevented dysphagia in breast cancer patients undergoing adjuvant radiotherapy: Results of a phase III randomized trial. Breast J. 2020;26:1882-1884.

Omega-3 Fatty Acids Prevent Oxaliplatin Neurotoxicity

One hundred seventy-nine Chinese patients with colon cancer who were receiving oxaliplatin combined with capecitabine were randomly assigned to receive, in double-blind fashion, capsules containing omega-3 fatty acids (346 mg of docosahexaenoic acid and 64 mg of eicosapentaenoic acid) or placebo three times a day, during chemotherapy and continuing for one month after chemotherapy was completed. All patients had six chemotherapy treatment cycles. The incidence of chemotherapy-induced peripheral neuropathy was significantly lower in the omega-3 group than in the placebo group (52.2% vs. 69.7%; p < 0.02). In addition, peripheral neuropathy was significantly less severe in the omega-3 group than in the placebo group (p < 0.02). Quality of life, as measured by the Global Health Status score on a questionnaire, was better in the omega-3 group than in the placebo group (p = 0.03).

Comment: Peripheral neuropathy is a common side effect of oxaliplatin and is its dose-limiting toxicity. In the present study, supplementation with omega-3 fatty acids decreased the incidence and severity of oxaliplatin-related neurotoxicity and improved quality of life in patients undergoing chemotherapy for colon cancer. The authors of the study suggested that the beneficial effect of omega-3 fatty acids was due to its antioxidant, anti-inflammatory, and neurotrophic effects.

Zhang X, et al. Prevention of oxaliplatin-related neurotoxicity by omega-3 PUFAs: A double-blind randomized study of patients receiving oxaliplatin combined with capecitabine for colon cancer. Medicine. 2020;99:e23564.

Curcumin for Polycystic Ovary Syndrome, or More Iranian Research Fraud?

Seventy-two overweight or obese Iranian women were randomly assigned to receive, in double-blind fashion, 500 mg of curcumin three times a day or placebo for three months. The mean fasting plasma glucose level and mean serum dehydroepiandrosterone level decreased to a significantly greater extent in the curcumin group than in the placebo group. In addition, curcumin significantly increased gene expression of peroxisome proliferator activated receptor gamma and the activity of glutathione peroxidase, and nonsignificantly increased gene expression of Sirtuin-1 and superoxide dismutase. The mean change in serum fasting insulin, luteinizing hormone, follicle-stimulating hormone, and estradiol did not differ significantly between groups.

Comment: The data cited above came from two different papers. Each paper apparently measured different laboratory parameters from the same study. That these papers were generated from the same study is supported by the following points: Both papers referred to the same document in the Iranian Registry of Clinical Trials (IRCT). In both papers, there were identical recruitment numbers: 112 patients were assessed for eligibility, 25 did not meet inclusion criteria, 8 declined to participate, and 7 were excluded for other reasons. As with numerous other studies coming from Iran, there are many aspects of these papers that make me wonder whether the research is fraudulent.

1. Discrepancy regarding recruitment periods: In one paper, the recruitment period was October 1, 2018, through the end of May 2019. In the other paper, the recruitment period was January 2019 through June 2019.
2. Discrepancies regarding body mass index (BMI): One of the papers and the IRCT document stated that the participants had to have a BMI between 25 and 30 kg/m². However, in the other paper, participants had to have a BMI greater than 25 kg/m², with no upper limit. In Table 2 of the first paper cited below, the baseline characteristics indicated BMIs ranging from 17.75 to 39.56 kg/m². These baseline BMIs violate the inclusion criteria on both the upper and lower end.
3. Discrepancy regarding inclusion criterion: One paper stated that participants had to be 18 to 49 years of age. The IRCT registration document stated that participants had to be 18 to 50. However, in both papers, the baseline characteristics indicated that at least one of the participants was 52 years old.
4. Discrepancy regarding study design: In the second paper cited below, it was stated that the participants came to the clinic only twice: at baseline and 12 weeks after starting the intervention. However, the paper also stated that the capsule packages were checked at the end of each month, and the number of remaining capsules was counted (presumably to assess compliance). It would not be possible to check the packages after one and two months if the participants did not return to the clinic until 12 weeks.
5. Ethical issue: One of the papers stated that the first patient was recruited on October 1, 2018. However, according to the IRCT document, the study was not approved by the ethics committee until October 28, 2018.
6. Issue regarding the placebo: One of the papers stated that the color of the placebo (maltodextrin) was “completely similar” to that of curcumin. However, curcumin is orange and maltodextrin is white. There was no mention of whether anything was added to the maltodextrin to change its color.
7. Discrepancy regarding funding: One paper stated that no funding was received. The other paper did not mention funding. The IRCT document stated that the study was funded by Iran University of Medical Sciences.

Heshmati J, et al. The effects of curcumin supplementation on oxidative stress, Sirtuin-1 and peroxisome proliferator activated receptor gamma coactivator 1alpha gene expression in polycystic ovarian syndrome (PCOS) patients: A randomized placebo-controlled clinical trial. Diabetes Metab Syndr. 2020;14:77-82.

Heshmati J, et al. Effects of curcumin supplementation on blood glucose, insulin resistance and androgens in patients with polycystic ovary syndrome: A randomized double-blind placebo-controlled clinical trial. Phytomedicine. 2021;80:153395.