Intravenous Vitamin C for Advanced Pancreatic Cancer

Thirty-four patients with stage IV pancreatic cancer who had not received prior chemotherapy and who had been recommended to receive gemcitabine and nab-paclitaxel chemotherapy were randomly assigned to receive or not to receive (control group) vitamin C intravenously (75 g 3 times a week). Patients who had contraindications to high-dose vitamin C therapy (i.e., those with glucose-6-phosphate dehydrogenase [G6PD] deficiency or inadequate renal function) were excluded from the study. Treatment continued until the disease progressed, the patient withdrew or died, or unacceptable toxicity occurred. Median overall survival time (16 months vs. 8.3 months; p = 0.03) and median progression-free survival time (6.2 months vs. 3.9 months; p < 0.03) were higher in the vitamin C group than in the control group. The vitamin C group had a longer median treatment time (179 days vs. 94 days) and a higher median total chemotherapy dose than the control group. There was a nonsignificant trend toward better quality of life in the vitamin C group than in the control group. Adding vitamin C did not increase the frequency or severity of adverse events.

Comment: In the 1970s, Nobel Laureate Linus Pauling and Scottish physician Ewan Cameron reported that treatment with 10 g per day of vitamin C markedly increased survival times in patients with terminal cancer. Because their trial was not randomized, the results were met with skepticism in the mainstream medical community. Subsequently, physicians at the Mayo Clinic conducted two randomized controlled trials and concluded that vitamin C was of no value as a treatment for advanced cancer. However, the Mayo Clinic trials had major flaws, the most serious of which was that many patients in the placebo group apparently knew they were not receiving vitamin C and were therefore taking large amounts of the vitamin surreptitiously. Because of the weaknesses of the Mayo Clinic trials, the issue of whether vitamin C is of value for cancer patients has remained unresolved.

The results of the present study provide strong evidence that high-dose vitamin C is beneficial at least for patients with advanced pancreatic cancer who are receiving a specific chemotherapy regimen. Further randomized controlled trials are warranted to determine what other types of cancer patients might benefit from this safe and relatively inexpensive treatment.

Bodeker KL, et al. A randomized trial of pharmacological ascorbate, gemcitabine, and nab-paclitaxel for metastatic pancreatic cancer. Redox Biol. 2024;77:103375.

Cinnamon Improves Blood Sugar Control in People with Prediabetes

Eighteen obese individuals (mean age, 51 years) with prediabetes were randomly assigned to receive, in double-blind fashion, 4 g per day of cinnamon powder (in capsules, taken with breakfast and dinner) or placebo (maltodextrin) for 4 weeks. After a 2-week washout period, each person received the alternate treatment for an additional 4 weeks. All participants consumed a low-fiber, low-polyphenol diet, beginning 2 weeks before the start of the study and continuing for the duration of the study. The mean 24-hour plasma glucose level (as determined by continuous glucose monitoring) was significantly lower during cinnamon treatment than during placebo treatment (p < 0.001). Compared with placebo, cinnamon treatment was associated with lower peak glucose levels during an oral glucose tolerance test (p < 0.03).

Comment: Several studies have found that cinnamon can improve blood glucose control in patients with diabetes. However, other studies have failed to confirm those findings. The results of the present study suggest that cinnamon is useful for obese people with prediabetes. The beneficial effect is thought to be due at least in part to the high polyphenol content of cinnamon, since some polyphenols have been reported to improve insulin sensitivity. Because the diet used in this study was low in polyphenols, it remains to be determined whether cinnamon would have the same effect on people who are not consuming a low-polyphenol diet. Foods rich in polyphenols include fruits, vegetables, whole grains, nuts, seeds, and black tea.

Zelicha H, et al. Effect of cinnamon spice on continuously monitored glycemic response in adults with prediabetes: a 4-week randomized controlled crossover trial. Am J Clin Nutr. 2024;119:649-657.

Safety Concern with Licorice

Twenty-eight healthy volunteers (mean age, 24 years) were randomly assigned to consume licorice (providing 100 mg per day of glycyrrhizic acid, as determined by an independent laboratory analysis) or no licorice for 2 weeks. After a 2-week washout period, each participant was crossed over to the other treatment for an additional 2 weeks. Mean systolic blood pressure increased by 3.1 mm Hg between the start and end of licorice consumption, and decreased by 0.3 mm Hg between the start and end of the control period (p < 0.02 for the difference in the change between treatment periods). Mean diastolic blood pressure increased by 1.9 mm Hg between the start and end of licorice consumption, and increased by 0.6 mm Hg between the start and end of the control period (p = 0.236 for the difference in the change between treatment periods).

Comment: Compounds present in licorice root (Glycyrrhiza glabra) slow the rate of breakdown of certain adrenal hormones (i.e., mineralocorticoids and glucocorticoids). Consumption of large amounts of licorice can cause side effects related to mineralocorticoid excess and, to a lesser extent, glucocorticoid excess. These side effects may include hypokalemia, hypertension, salt and fluid retention, and heart failure. Myopathy and rhabdomyolysis have occurred in cases of severe hypokalemia.

The World Health Organization has suggested that 100 mg per day of glycyrrhizic acid (an amount present in about 50 g per day of licorice candy) would be unlikely to cause adverse effects, but the results of the present study suggest that even this relatively small amount can raise blood pressure after as little as 2 weeks. People who are regularly consuming licorice products should monitor their blood pressure and serum potassium level.

Af Geijerstam P, et al. A low dose of daily licorice intake affects renin, aldosterone, and home blood pressure in a randomized crossover trial. Am J Clin Nutr. 2024;119:682-691.

Can Lutein and Related Carotenoids Prevent Cardiovascular Disease?

Ninety-seven healthy Irish individuals (mean age, 45 years) were randomly assigned to receive, in double-blind fashion, a daily carotenoid supplement (10 mg of lutein, 20 mg of meso-zeaxanthin and 2 mg of zeaxanthin) or placebo (sunflower oil) for 6 months. Compared with placebo, the carotenoid supplement decreased mean serum concentrations of inflammatory cytokines (interleukin 1-beta [p < 0.001] and tumor necrosis factor-alpha [p = 0.003]) and decreased the mean serum concentration of oxidized low-density lipoprotein) (LDL) (p < 0.01).

Comment: Lutein and zeaxanthin are carotenoids that are present in foods such as spinach, kale, other dark green leafy vegetables, egg yolks, corn, grapes, oranges, squash, and zucchini. The human body concentrates these carotenoids in the macular region of the retina, where they appear to prevent the development of age-related macular degeneration by blocking the blue-light portion of the sun’s rays. meso-Zeaxanthin is also present in the macula (it is apparently synthesized in vivo from lutein), although it is not present in any appreciable amount in food.

Systemic inflammation and oxidation of LDL are thought to play a role in the pathogenesis of atherosclerosis. The results of the present study suggest that lutein and related carotenoids exert an anti-inflammatory effect and also prevent LDL from becoming oxidized. These effects would be expected to prevent the development of atherosclerosis.

Egg yolks contain relatively large amounts of both cholesterol and lutein. It has been suggested that eggs may be atherogenic because of their high cholesterol content. However, observational studies have failed to provide any clear evidence that eating eggs is harmful to the cardiovascular system. If the high cholesterol content of egg yolks is harmful to some extent, this effect might be counterbalanced by the lutein present in egg yolks.

Stringham NT, et al. Lutein, zeaxanthin, and meso-zeaxanthin supplementation attenuates inflammatory cytokines and markers of oxidative cardiovascular processes in humans. Nutr Metab Cardiovasc Dis. 2024;34:1976-1983.

Is Coconut Water an Effective Treatment for Ulcerative Colitis?

Ninety-five patients (mean age, 37 years) living in India with mild-to-moderate active ulcerative colitis (median disease duration, 48 months for active treatment, 42 months for placebo) received standard medical therapy and were randomly assigned to receive, in double-blind fashion, 200 ml of coconut water or placebo twice a day for 8 weeks. Outcome measures included clinical remission (Simple Clinical Colitis Activity Index [SCCAI] of 2 or less) and clinical response (SCCAI decline of at least 3 points). The clinical response rate (57.1% vs. 28.3%; p = 0.01) and remission rate (53.1% vs. 28.3%; p = 0.02) were significantly higher with coconut water than with placebo. Adverse events did not differ between groups.

Comment: Coconut water has demonstrated anti-inflammatory activity and can modulate the gut microbiome (which may be beneficial for some people with inflammatory bowel disease). The results of the present study suggest that coconut water is safe and effective for inducing clinical remission and overall clinical improvement in patients with mild-to-moderate ulcerative colitis.

The effect size of coconut water in this study was surprisingly large for a nontoxic natural substance. According to the data, for every 3.47 patients given coconut water, one would have clinically meaningful improvement who otherwise would not have experienced that level of improvement. And for every 4 patients given coconut water, one would achieve clinical remission who otherwise would not have achieved remission. In my extensive review of the research on natural medicine during my 51-year career, I have developed the impression that some research coming from India is of questionable reliability. Confirmatory studies are therefore needed before the effectiveness of coconut water can be considered proven.

Kedia S, et al. Coconut water induces clinical remission in mild to moderate ulcerative colitis: double-blind placebo-controlled trial. Clin Gastroenterol Hepatol. 2024;22:1295-1306.

N-acetylcysteine for Bronchiectasis

Seventeen patients with bronchiectasis were randomly assigned to receive, in double-blind fashion, 1,200 mg of N-acetylcysteine (NAC) or placebo twice a day for 6 weeks. Patients were excluded if they had cystic fibrosis, if they were current smokers, or if they had a history of more than 20 pack-years of smoking. Mean age was 72 years in the NAC group and 62 years in the placebo group. Mean forced vital capacity increased by 10% in the NAC group compared with the change in the placebo group (p = 0.045). Compared with placebo, NAC treatment resulted in significant improvements in coughing and in limitations of activity. Adverse effects were similar in both groups.

Comment: Bronchiectasis is a chronic lung disorder characterized by irreversible dilatation of one or more bronchi. It frequently results from recurrent infection or inflammation and is seen in many patients with cystic fibrosis. Symptoms may include chronic cough with mucopurulent sputum production, impaired clearance of secretions, shortness of breath, and hemoptysis. Medical therapy includes antibiotics and regular drainage to remove bronchial secretions.

Orally administered NAC has been shown in numerous studies to be beneficial for patients with chronic obstructive pulmonary disease (COPD). Beneficial effects included fewer disease exacerbations, an improvement in sputum viscosity, and a reduction in dyspnea and cough. These effects of NAC may be mediated in part by an improvement in the clearance of mucus by pulmonary cilia, a mucolytic effect, and an increase in the synthesis of glutathione.¹ The results of the present study suggest that NAC may also be of value for patients with bronchiectasis.

Jayaram L, et al. Evaluation of high dose N-Acetylcysteine on airway inflammation and quality of life outcomes in adults with bronchiectasis: A randomised placebo-controlled pilot study. Pulm Pharmacol Ther. 2024;84:102283.

Is Vitamin D Beneficial for Benign Paroxysmal Positional Vertigo?

Thirty-eight patients (mean age, 56 years) with benign paroxysmal positional vertigo (BPPV) who had been successfully treated with canalith repositioning procedures and who had a serum 25-hydroxyvitamin D level less than 20 ng/ml were randomly assigned to receive, in double-blind fashion, vitamin D (7,000 IU once a week) or placebo for 1 year. Thirty-seven patients were followed for 6 months and 30 were followed for 12 months. The cumulative recurrence rate of BPPV was lower at 6 months (5.3% vs. 26.7%; p = 0.146) and at 12 months (9.5% vs. 44.4%; p = 0.10) in the vitamin D group than in the placebo group.

Comment: BPPV is a common cause of intermittent vertigo. It is usually triggered by certain changes in head position. BPPV is caused by the presence of small calcium crystals in a portion of the inner ear. The condition is often effectively treated with canalith repositioning procedures, which are a series of head movements designed to move the calcium crystals to a different place in the inner ear.

The results of the present study suggest that vitamin D supplementation can reduce the recurrence rate in people with BPPV. However, since the effect of vitamin D was only of borderline statistical significance, larger studies are needed to confirm the possible beneficial effect of vitamin D.

Kong TH, et al. Vitamin D supplementation in preventing the recurrence of benign paroxysmal positional vertigo. Laryngoscope Investig Otolaryngol. 2024;9:e1225.

Many Pregnant Women are not Consuming Enough Choline

In a study of 2,996 Canadian women participating in the Canadian CHILD cohort study, during the second trimester of pregnancy only 24.8% of the women met the Adequate Intake recommendation for dietary choline (at least 450 mg per day). Mean choline intake was only 375 mg per day.

Comment: Choline is an essential nutrient for fetal and infant brain development. When pregnant rats were fed a choline-deficient diet, the offspring had impaired cognitive function, both early in life and during adulthood. In contrast, feeding a high-choline diet (as compared with a normal amount of choline) during pregnancy resulted in improved cognitive function in the offspring, both early in life and during adulthood.² The results of the present study suggest that many pregnant women are not consuming adequate amounts of choline. For those women, a choline supplement may be worthwhile. Good food sources of choline include eggs, soybeans, fish, chicken, beef, wheat germ, and whole wheat. 

Wiedeman AM, et al. Women in Canada are consuming above the upper intake level of folic acid but few are meeting dietary choline recommendations in the second trimester of pregnancy: data from the CHILD cohort study. Appl Physiol Nutr Metab. 2024;49:868-873.

References

1. Gaby AR. Chronic obstructive pulmonary disease. In Gaby AR. Nutritional Medicine, Third Edition. Concord NH, 2024, chapter 96 (www.doctorgaby.com).

2. Meck WH, Williams CL. Simultaneous temporal processing is sensitive to prenatal choline availability in mature and aged rats. Neuroreport. 1997;8:3045-51.