Quercetin for Nonalcoholic Fatty Liver Disease

Forty-one Chinese patients (mean age, 40 years) with nonalcoholic fatty liver disease (mean body mass index, 28 kg/m²) were randomly assigned to receive, in double-blind fashion, 500 mg of quercetin once a day or placebo for 12 weeks. After a 4-week washout period, each patient received the alternate treatment for an additional 12 weeks. In intent-to-treat analysis, the mean intrahepatic lipid content decreased from 11.5% to 9.6% during quercetin treatment, whereas the value was 11.1% with placebo both before and after treatment (p = 0.013 for the difference in the change between treatments). Mean body weight decreased by 1.5 kg during quercetin treatment and by 0.3 kg during placebo treatment (p < 004 for the difference in the change between treatments). There was a significant correlation during both quercetin treatment and placebo treatment between the reduction in body weight and the reduction in intrahepatic lipid content.

Comment: Quercetin is a flavonoid present in apples, black tea, onions, berries, and various other plant foods. In this study, supplementation with quercetin decreased intrahepatic lipid content in patients with nonalcoholic fatty liver disease. Patients lost more weight with quercetin than with placebo, and the reduction in liver-fat content may have been due at least in part to weight loss. There is no obvious mechanism to explain how quercetin promoted weight loss, and there are no other obvious mechanisms by which quercetin might decrease hepatic lipid infiltration. The average diet contains about 25 mg of quercetin. While consuming more high-quercetin foods would increase dietary quercetin intake, achieving an intake level of 500 mg per day or more would in most cases require supplementation.

Li N, et al. Quercetin intervention reduced hepatic fat deposition in patients with nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled crossover clinical trial. Am J Clin Nutr. 2024;120:507-517.

Many Americans are Not Consuming Enough Iodine

Iodine intake of US girls and women was examined using dietary recall data and urinary iodine concentrations among participants in the United States National Health and Nutritional Examination Survey. Median iodine intake of girls and nonpregnant, nonlactating women declined between 2011 and 2020 in all three age groups examined (14 years or younger, 15 to 49, and 50 or older). Median iodine intake of pregnant and lactating women also declined. In the 2017-2020 period, the proportion of women who had inadequate iodine intake as assessed by urinary iodine concentrations was 48.8% for nonpregnant, nonlactating women of reproductive age (15-49 years), 63.2% for pregnant women, and 31.3% for lactating women.

Comment: Adequate iodine intake is essential for normal thyroid function. In addition, iodine deficiency during pregnancy can lead to hypothyroidism in the fetus, which can result in developmental deficits, including mental disability. The present study found that iodine intake among U.S. girls and women declined between 2011 and 2020, and that inadequate intake is common. The decrease in dietary iodine consumption may be due in part to a reduction in consumption of milk, which is a significant source of this trace mineral. Other important sources of iodine include meat, fish, poultry, eggs, kelp and other seaweeds, and iodized salt.

Some multivitamin-multimineral products contain iodine, but many do not. A reasonable amount of iodine to include in a nutritional supplement would be around 150 µg per day. Excessive iodine intake can interfere with thyroid function and can cause acne and a number of other side effects. According to the Food and Nutrition Board of the Institute of Medicine of the US National Academy of Sciences, the Tolerable Upper Intake Level (UL) for iodine is 1,100 µg per day for adults. The UL is defined as “the highest average daily nutrient intake level that is likely to pose no risk of adverse health effects to almost all individuals in the general population.” Larger doses of iodine are sometimes used therapeutically, such as in the treatment of fibrocystic breast changes or some types of infections. However, high-dose iodine therapy should be monitored by a healthcare practitioner.

Sun H, Weaver CM. Iodine intake trends in United States girls and women between 2011 and 2020. J Nutr. 2024;154:928-939.

Is Vitamin D Helpful for “Long-COVID?”

Eighty patients (mean age, 34 years) living in Thailand with post-COVID fatigue or neuropsychiatric symptoms (e.g., anxiety, depression, sleep disturbances, or cognitive impairment) were randomly assigned to receive, in double-blind fashion, 60,000 IU of vitamin D₂ once a week or placebo for eight weeks. The mean serum 25-hydroxyvitamin D level at baseline was 18.1 ng/ml. Compared with placebo, significant improvements were seen in the vitamin D group on scales that measured fatigue, anxiety, and cognitive impairment, and a nonsignificant improvement was seen on a scale that measured depression (p = 0.085). No significant side effects were seen.

Comment: Long-COVID (also called post-COVID syndrome) is defined as a chronic condition that occurs after a COVID-19 infection and lasts at least three months. The symptoms may resemble those of chronic fatigue syndrome, and may include severe fatigue, problems with memory, lightheadedness, and impaired taste or smell. Some studies have found that vitamin D supplementation can accelerate recovery from an acute COVID-19 infection, but other studies have failed to confirm those findings. In the present study, vitamin D supplementation improved fatigue, anxiety, and cognitive function in patients with post-COVID syndrome. The bulk of vitamin D research has found that vitamin D₃ is preferable to vitamin D₂ (in terms of both safety and efficacy), and that daily administration of smaller doses is preferable to weekly administration of larger doses.

Charoenporn V, et al. Effects of an 8-week high-dose vitamin D supplementation on fatigue and neuropsychiatric manifestations in post-COVID syndrome: A randomized controlled trial. Psychiatry Clin Neurosci. 2024;78:595-604.

Vitamin K₂ for Nocturnal Leg Cramps

One hundred ninety-nine Chinese individuals aged 65 years or older (mean age, 72.3 years) with nocturnal leg cramps a mean of 2.66 times per week were randomly assigned to receive, in double-blind fashion, 180 µg per day of menoquinone-7 (MK-7, a form of vitamin K₂) or placebo for 8 weeks. Two-thirds of the participants had hypertension and half had diabetes. During the study, the mean number of nocturnal leg cramps per week was lower in the MK-7 group than in the placebo group (0.96 vs. 3.63; p < 0.001). Mean duration of the cramps was significantly lower in the MK-7 group than in the placebo group (15 vs. 59 seconds). Mean severity of cramps was also significantly lower by 46% in the MK-7 group than in the placebo group.

Comment: Nocturnal leg cramps are a common problem, particularly among elderly individuals. In the present study, MK-7 decreased the frequency, duration, and severity of nocturnal leg cramps in elderly Chinese individuals. The mechanism of action is not known. Other nutritional treatments that have been reported to be effective for nocturnal leg cramps include magnesium, vitamin E, and intramuscular injections of vitamin B₁₂.

Tan J, et al. Vitamin K2 in managing nocturnal leg cramps: a randomized clinical trial. JAMA Intern Med. 2024;184:1443-1447.

Prunes (dried plums) for Osteoporosis

Two hundred thirty-five postmenopausal women (mean age, 62 years) in the United States were randomly assigned to consume 50 g per day of prunes (equivalent to 5-6 prunes), 100 g per day of prunes (equivalent to 10-12 prunes), or no prunes for 12 months. The mean cortical volumetric (3-dimensional) bone mineral density at the tibia and estimated bone strength decreased in the control group and did not change in the groups receiving prunes (both groups combined). The difference in the change between groups was significant both for bone mineral density (p = 0.012) and for estimated bone strength (p = 0.024). Prune consumption had no significant effect on bone mineral density at the radius.

Comment: This study supports previous research¹ demonstrating that consumption of prunes can slow bone loss in postmenopausal women. In the previous study, 50 g per day and 100 g per day of prunes produced similar results. There is evidence that consumption of prunes can decrease bone resorption and can also increase osteoblastic activity (which promotes new bone formation). It has been suggested that the active substance in prunes is a polyphenol.

Koltun KJ, et al. Prunes preserve cortical density and estimated strength of the tibia in a 12-month randomized controlled trial in postmenopausal women: The Prune Study. Osteoporos Int. 2024;35:863-875.

Omega-3 Fatty Acid for Migraine Prevention

Seventy individuals (mean age, 39.5 years) living in Taiwan who suffered from episodic migraines were randomly assigned to receive, in double-blind fashion, 900 mg of eicosapentaenoic acid (EPA; from 1 g of ethyl-EPA) twice a day with breakfast and dinner or placebo (soybean oil) for 12 weeks. The mean number of migraine days per month decreased by 4.4 days (from 7.4 days to 3.0 days) in the EPA group and by 0.6 days (from 6.7 days to 6.1 days) in the placebo group (p = 0.001 for the difference in the change between groups). Mean migraine severity and scores on a scale that measured quality of life also improved to a significantly greater degree in the EPA group than in the placebo group. No significant side effects were seen.

Comment: In this study, supplementation with the long-chain omega-3 fatty acid EPA decreased both the frequency and severity of migraines in people with recurrent migraines. Other double-blind studies have found that administration of a similar amount of EPA in the form of fish oil was also useful for migraine prophylaxis. The beneficial effects of EPA may be due to its anti-inflammatory action, since inflammation has been implicated as a factor in the pathogenesis of migraine.

Wang HF, et al. A 12-week randomized double-blind clinical trial of eicosapentaenoic acid intervention in episodic migraine. Brain Behav Immun. 2024;118:459-467.

Vitamin C Supplementation of Pregnant Smokers Improves Airway Function in the Children

Two hundred fifty-one pregnant cigarette smokers were randomly assigned to receive, in double-blind fashion, 500 mg per day of vitamin C or placebo, beginning at a mean of 18 weeks of gestation. One hundred ninety-two children had a pulmonary function test (forced expiratory flow) at 5 years of age, and 213 children were available for assessment of wheezing. Mean forced expiratory flow was 17.2% higher in the children of women given vitamin C than in the children of women given placebo (p < 0.001). The proportion of children who experienced wheezing was lower in the vitamin C group than in the placebo group (28.3% vs. 47.2%; p = 0.003).

Comment: In this study, vitamin C supplementation of pregnant smokers improved airway function of their children at age 5 years and decreased the occurrence of wheezing. Previous studies found that supplementation with a modest amount of vitamin C (100 mg per day) during pregnancy reduced the incidence of premature rupture of membranes and of urinary tract infections in women who were not selected on the basis of whether or not they were smokers. Since cigarette smoking increases vitamin C requirements, vitamin C supplementation may be especially important for pregnant women who smoke. Smoking during pregnancy can cause serious health problems, and pregnant women should be strongly encouraged not to smoke. However, for those who are unable to quit, vitamin C supplementation could mitigate some of the damage caused by smoking.

McEvoy CT, et al. Effect of vitamin C supplementation for pregnant smokers on offspring airway function and wheeze at age 5 years: follow-up of a randomized clinical trial. JAMA Pediatr. 2023;177:16-24.

Can Omega-3 Fatty Acids Help Dissolve Gallstones?

Forty-five patients in South Korea with radiolucent gallstones with a diameter of 15 mm or less, who had no symptoms or mild symptoms, were treated with ursodeoxycholic acid (200 mg 3 times per day with meals) or ursodeoxycholic acid plus omega-3 fatty acids (1,000 mg of Omacor 3 times per day with meals) for 6 months. Each 1,000 mg of Omacor contained around 460 mg of eicosapentaenoic acid and 380 mg of docosahexaenoic acid. The primary outcome measures were the gallstone dissolution rate (defined as the percentage change in gallstone size from baseline to 6 months) and the response rate (defined as the proportion of patients who showed any improvement). The gallstone dissolution rate was nonsignificantly higher in the group receiving combination therapy than in those receiving ursodeoxycholic acid alone (45.7% vs 9.9%; p = 0.07). The radiological response rate was significantly higher in the group receiving combination therapy (90.5% vs. 41.7%; p = 0.007). In both groups, dissolution and response rates were higher in patients with gallbladder sludge than in those with distinct stones. No serious adverse events were observed, and the incidence of adverse events was similar in the 2 groups.

Comment: Ursodeoxycholic acid is a bile acid that has been used to promote the dissolution of radiolucent gallstones. The results of the present study suggest that the combination of ursodeoxycholic acid and omega-3 fatty acids is more effective than ursodeoxycholic acid alone for dissolving radiolucent gallstones. Other research suggests that omega-3 fatty acids may work by decreasing the cholesterol saturation of bile.

Lee SY, et al. Gallstone dissolution effects of combination therapy with n-3 polyunsaturated fatty acids and ursodeoxycholic acid: a randomized, prospective, preliminary clinical trial. Gut Liver. 2024;18:1069-1079.

Reference

1. Hooshmand S, et al. The effect of two doses of dried plum on bone density and bone biomarkers in osteopenic postmenopausal women: a randomized, controlled trial. Osteoporos Int. 2016;27:2271-2279.