Alan R. Gaby, MD

Is Zinc Effective Against Molluscum Contagiosum?

Twenty-three Turkish children (mean age, 2.5 years) with molluscum contagiosum received oral zinc for two months. The dosage was 3 mg per day (as zinc sulfate) for ages three years or younger and 5 mg per day for older children. Three months after the start of zinc treatment the lesions had resolved in six children. At five months after the start of treatment, the lesions had resolved in 19 of the 23 children (83%). None of the children whose lesions resolved had a recurrence over the next 12 months. The mean serum zinc level prior to treatment did not differ between children with molluscum contagiosum and age-matched controls.

Comment: Molluscum contagiosum is viral skin infection that occurs most commonly in children. The condition usually resolves in six to 12 months, but in some cases it may last up to four years. Zinc has antiviral activity and plays a role in immune function, effects that might be useful in the treatment of molluscum contagiosum. Controlled trials are needed to determine to what extent the improvements seen in this study were due to zinc therapy, as opposed to spontaneous remission.

Vehapoglu A. Is molluscum contagiosum related to zinc deficiency in children? Effectiveness of oral zinc sulfate therapy in lesion regression. Nutrition. 2021;91-92:111418.

Niacinamide for Actinic Keratoses

A man in his mid-60s presented with extensive actinic keratoses on his forehead and scalp. He had male pattern baldness and a history of frequent sunburn of the scalp. He had undergone surgery on four separate occasions for invasive squamous cell carcinoma of the scalp. The patient had previously been treated with photodynamic therapy and with topical ingenol mebulate. Both of these treatments produced good results, but the lesions recurred. He was then tried on topical retinoids but developed erosive pustulosis of the scalp, and the treatment was stopped. In April 2019 the man was started on niacinamide (500 mg twice a day), and there was a dramatic decrease in the number of actinic keratoses. Niacinamide was continued and during the next eight months no new lesions appeared.

Comment: Previous studies have shown that oral niacinamide can decrease the number of actinic keratoses and prevent the progression of actinic keratoses to non-melanoma skin cancer.^1,2 Niacinamide may work in part by preventing ultraviolet light-induced immunosuppression. In the previous research, the beneficial effect of niacinamide wore off after treatment was discontinued. In the present case report, the benefits of niacinamide therapy persisted with continued treatment. Thus, ongoing treatment with niacinamide may be necessary to maintain the beneficial effects against actinic keratoses and non-melanoma skin cancer. A niacinamide dose of 500 mg twice a day is generally safe, although larger doses (such as 3,000 mg per day or more) has occasionally caused liver damage.

Paugam C, Dreno B. Is nicotinamide a sustainable therapy for resistant actinic keratoses? J Eur Acad Dermatol Venereol. 2020;34:e624-e626.

Magnesium for Familial Benign Chronic Pemphigus

A 42-year-old woman with familial benign chronic pemphigus (Hailey-Hailey disease) had only a partial response to topical and systemic glucocorticoids and antibiotics, topical tacrolimus, dapsone, and botulinum toxin. Based on previous case reports, she was treated with 300 mg per day of magnesium, as a solution of magnesium chloride in water. The lesions completely resolved in four weeks. Subsequently there was a mild recurrence of some of the lesions, which resolved rapidly after the dosage of magnesium was doubled.

Comment: Hailey-Hailey disease is a rare autosomal dominant skin disease, occurring in about 1 in 50,000 individuals. It presents with eroded, macerated, vegetating, malodorous plaques in the intertriginous regions. Secondary infections are common. Although various medications may improve Hailey-Hailey disease, it is often difficult to control and in many cases is a debilitating condition. The patient described above had a dramatic improvement after taking a magnesium supplement. A similar dramatic response was observed in a previous case report.³ Although the success of magnesium in patients with this difficult-to-treat genetic condition might seem too good to be true, there is nothing to be lost by trying this safe and inexpensive treatment. Several case reports suggest that low-dose naltrexone is also effective against Hailey-Hailey disease, and that the combination of magnesium and low-dose naltrexone is more effective than either treatment by itself.

Dos Santos Garcia MC, et al. Successful treatment of refractory Hailey-Hailey disease with oral magnesium chloride. Dermatol Ther. 2020;33:e14429.

Almonds for Facial Wrinkles

Fifty-six postmenopausal women (mean age, 63.4 years) with Fitzpatrick skin types I or II (light skin) were randomly assigned to consume 20% of their daily energy as almonds or a calorie-matched snack (pretzels, granola bars, and fig bars) for 24 weeks. Participants in both groups were advised to avoid all other nut-containing foods and nut oils. Facial photographs and an image analysis system were used to obtain standardized high-resolution photographs and information on wrinkle width and severity. Compared with baseline, mean wrinkle severity decreased in the almond group by 15% at week 16 (p = 0.02 vs. the control diet) and by 16% at week 24 (p < 0.02 vs. the control diet). Mean facial pigment intensity decreased by 20% at week 16 (p = 0.02 vs. the control diet) and this improvement was maintained at week 24.

Comment: The results of this study suggest that consumption of almonds can improve facial wrinkles and decrease skin pigmentation in postmenopausal women with Fitzpatrick skin types I and II. This study confirms a previous shorter-term study by the same research group. The authors suggested that the beneficial effect of almonds may be due to its fatty acid and antioxidant content. Other research has found that eating almonds may improve LDL-cholesterol levels and decrease insulin resistance.

Rybak I, et al. Prospective randomized controlled trial on the effects of almonds on facial wrinkles and pigmentation. Nutrients. 2021;13:785.

Magnesium for Migraines, or More Iranian Research Fraud?

Two hundred sixty Iranian adults with recurrent migraines were randomly assigned to receive, in double-blind fashion, sodium valproate (200 mg twice a day), magnesium oxide (250 mg twice a day), or both treatments for 12 weeks. A significant decrease in frequency, severity, and duration of migraine attacks was seen in each group. Mean headache severity, duration of headaches, and number of analgesics used were significantly lower in the group receiving combination therapy than in the group receiving sodium valproate alone. The authors concluded that magnesium enhanced the effect of sodium valproate as a prophylactic medication in patients with recurrent migraines.

Comment: There is ample evidence from previous studies that magnesium supplementation is beneficial for migraine prophylaxis. However, as Townsend Letter readers know, I have concerns that many of the research papers coming from Iran appear to be fraudulent. Several issues in the study described above raise questions about its credibility.

1. Dangerous treatment protocol: Sodium valproate is teratogenic and has been associated with severe birth defects, including neural tube defects. The neural tube forms during the second week of pregnancy, when many women do not yet know they are pregnant. For that reason, authorities advise against the use of sodium valproate by women who have the potential to become pregnant, unless the treatment is absolutely necessary. In the present study, 56% of the participants were female, and with a mean age of 35.5 years, more than half were of childbearing age. According to treatment guidelines, women of childbearing age who are taking sodium valproate should be advised of the risks, should use effective contraception, and should be supervised closely. There is no evidence that these actions were taken in this study. One wonders whether the risks of sodium valproate and the need for contraception were discussed in the informed-consent document, considering that 9 of 125 women became pregnant during the 12-week trial. If the women in this study had been advised of the risks, it is unlikely that many of them would have agreed to participate, particularly since other medications for migraine prophylaxis are safe during pregnancy. It is also unlikely that the Ethics Committee of Qom University of Medical Sciences would have approved the study if they had been aware of the risks.
2. Implausible treatment protocol: At the beginning of the study, each participant underwent a one-month run-in period during which they were not given any medication for migraine prophylaxis. It is difficult to believe that anyone would have agreed to participate in such a study, let alone nearly 100% of the subjects who fulfilled the inclusion criteria. The people who enrolled in this study had been referred to a neurology clinic with a mean score of 21.85 on the Migraine Disability Assessment Test (scores of 21 or higher correspond to severe disability). Patients with severe migraines are looking for relief, not to participate in a study that requires them to wait a month before their treatment starts (and also to discontinue any prophylactic medication they were currently taking).
3. Discrepancy regarding funding: The paper stated that the study did not receive any funding. The Iranian Registry of Clinical Trials (IRCT) document that is associated with this study stated that the study was funded by Qom University of Medical Sciences.
4. Discrepancies regarding inclusion and exclusion criteria: One of the inclusion criteria in the paper was having at least four migraine attacks per month. In the IRCT document the inclusion criterion was having at least two migraine attacks per month. The paper stated that patients were excluded if they were taking supplements containing magnesium. The IRCT document stated that patients were excluded if they were taking supplements containing magnesium, calcium, or riboflavin.
5. Discrepancies regarding outcome measures: In the paper the primary outcome measure was migraine frequency. Secondary outcome measures were migraine severity, duration of attacks, and number of pain medicines used. In the IRCT document, all four of these outcome measures were listed as primary outcome measures.

Khani S, et al. Comparative study of magnesium, sodium valproate, and concurrent magnesium-sodium valproate therapy in the prevention of migraine headaches: a randomized controlled double-blind trial. J Headache Pain. 2021;22:21.

Calcifediol (25-hydroxyvitamin D) for COVID-19

An observational study was conducted from March to May 2020 among 838 patients admitted to COVID-19 wards of a hospital in Barcelona, Spain. Four hundred forty-seven patients received calcifediol (25-hydroxyvitamin D), whereas 391 patients (controls) did not receive calcifediol at the time of hospital admission. The dosage of calcifediol was 532 µg on day 1 and 266 µg on days 3, 7, 15, and 30. The proportion of patients who required admission to the intensive care unit (ICU) was significantly lower in patients treated with calcifediol than in the control group (4.5% vs. 21%; p < 0.001). After adjustment for age, sex, 25-hydroxyvitamin D levels at baseline, and comorbidities, patients given calcifediol had a reduced risk of requiring ICU treatment (odds ratio = 0.13; 95% confidence interval [CI], 0.07-0.23). The mortality rate was 4.7% in the calcifediol group and 15.9% in the control group (p = 0.001). After adjustment for potential confounding variables, the odds ratio for mortality was 0.21 (95% CI, 0.10-0.43).

Comment: In a previous randomized trial conducted in Cordoba, Spain, treatment of hospitalized COVID-19 patients with calcifediol (according to a protocol similar to that described above) decreased disease severity and markedly decreased the need for admission to the ICU. The results of the present observational study are consistent with the findings of the previous study.

Vitamin D is converted in vivo to calcifediol, so it would be reasonable to assume that vitamin D would also have some degree of efficacy against COVID-19. That assumption is supported by one previous study.⁴ Widespread use of calcifediol in the United States for COVID-19 is not feasible because it is a prescription drug and because it is very expensive (more than $1,200 for a course of treatment). In contrast, vitamin D is inexpensive and can be obtained without a prescription. Vitamin D therefore seems to be a better candidate than calcifediol for routine use against COVID-19.

It is not clear what dosage of vitamin D would be equivalent to the dosages of calcifediol used in the study described above. A dose of 532 µg of vitamin D3 (the amount of calcifediol given on the first day) is equal to 21,200 IU. However, calcifediol is considered to be more potent than vitamin D because it produces greater increases in serum 25-hydroxyvitamin D concentrations.⁵

Nogues X, et al. Calcifediol treatment and COVID-19- related outcomes. J Clin Endocrinol Metab. 2021;106:e4017-e4027.

Modern Medicine Is Dangerous

The authors of this study estimated the number of visits from 2017 through 2019 to emergency departments (EDs) in the United States that were due to adverse reactions to medications. The estimate was based on visits to 60 EDs participating in the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance Project. Adverse reactions were based on clinicians’ diagnoses and supporting data documented in the medical record. Based on 96,925 ED visits for adverse reactions to medication, there were an estimated 6.1 such visits per 1,000 population per year, and 38.6% of these visits resulted in hospitalization. Rates of ED visits were higher for patients aged 65 years or older than for those younger than 65 (12.1 vs 5.0 per 1,000 population per year). An estimated 69.1% of ED visits for adverse reactions to medication involved therapeutic use of the medication (defined as “use as directed or unintentional errors by adults or adolescents”). Among ED visits involving therapeutic use of medications, the proportion of visits due to certain drug classes were as follows: anticoagulants (21.5%), diabetes agents (13.7%), antibiotics (12.8%), antiplatelet drugs (7.8%), analgesics (6.6%), renin/angiotensin system inhibitors (3.8%), sedative/hypnotic agents (2.4%), beta-blockers (1.6%), and other cardiovascular agents (excluding renin/angiotensin system inhibitors and beta-blockers (3.9%).

Comment: This study demonstrates that around 2 million Americans visit an ED every year because of adverse effects of medications. That is a shockingly high number, especially considering that the medical profession purports to live by the adage, “Above all do no harm.” No treatment is entirely safe, and it is inevitable that some patients will be injured by treatments that are designed to help them. However, practitioners can dramatically decrease the risk of harming their patients by emphasizing safer treatments such as dietary modifications, exercise, stress reduction, and appropriate use of nutritional supplements, botanicals, and other natural substances. Many papers have been written about how dangerous conventional medical therapies can be. I store these papers in a filing cabinet in a file labeled “Iatrogenesis.” This file has gotten rather thick over the years. Fortunately, more and more practitioners are offering approaches that can decrease the need for dangerous medications, and more and more patients are embracing that approach.

Budnitz DS, et al. US emergency department visits attributed to medication harms, 2017-2019. JAMA. 2021;326:1299-1309.

Dutch Doctors Are More “With It” Than American Doctors

A questionnaire was sent to pediatricians and pediatric residents in one academic hospital and six community teaching hospitals in the Netherlands, to examine the use of intravenous magnesium in children with acute asthma. Of 111 practitioners who responded, 96% reported regular use of this treatment. Ninety-three percent of practitioners who used intravenous magnesium for acute asthma were convinced that it was effective.

Comment: A large body of evidence has shown that intravenous magnesium is an effective treatment for acute asthma and may decrease hospitalizations by as much as 30%. Dutch treatment guidelines recommend that practitioners consider intravenous magnesium for children with acute asthma who fail to respond to first-line treatment. The results of this study indicate that Dutch practitioners are, for the most part, following these guidelines.

In the United States, guidelines from the National Heart, Lung and Blood Institute of the National Institutes of Health recommend intravenous magnesium as adjunctive treatment for asthma in the emergency department (ED). However, a study conducted in seven EDs in the United States found that, among 61,854 children presenting with acute asthma, intravenous magnesium was administered in only 10.5% of cases. During 22,495 visits resulting in hospitalization after ED treatment, intravenous magnesium was administered in only 25.7% of cases. Among children who did receive magnesium, the median time in the ED before they received it was slightly more than 2.5 hours.⁶

Thus, Dutch doctors are, for the most part, providing higher-quality care than their American counterparts with respect to treating acute asthma in children. I do not know why US doctors are failing to use this effective and inexpensive treatment. But I do know, based on this and other evidence, that we have no right to claim the US provides the best and most evidence-based healthcare in the world.

van Weelden M, et al. Intravenous magnesium sulphate in children with acute wheeze: a nationwide survey. J Asthma. 2021;58:1444-1450.

This article was originally published in Townsend Letter, April 2022.

References

1. Surjana D, et al. Oral nicotinamide reduces actinic keratoses in phase II double-blinded randomized controlled trials. J Invest Dermatol. 2012;132:1497-500.
2. Chen AC, et al. A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention. N Engl J Med. 2015;373:1618-26.
3. Borghi A, et al. Efficacy of magnesium chloride in the treatment of Hailey-Hailey disease: from serendipity to evidence of its effect on intracellular Ca(2+) homeostasis. Int J Dermatol. 2015;54:543-548.
4. Annweiler C, et al. Vitamin D and survival in COVID-19 patients: A quasi-experimental study. J Steroid Biochem Mol Biol. 2020;204:105771.
5. Quesada-Gomez JM, Bouillon R. Is calcifediol better than cholecalciferol for vitamin D supplementation? Osteoporos Int. 2018;29:1697-1711.
6. Johnson MD, et al. Intravenous magnesium in asthma pharmacotherapy: variability in use in the PECARN registry. J Pediatr. 2020;220:165-174.e2.

Published March 23, 2024

About the Author

Alan R. Gaby, MD, is the author of the textbook, Nutritional Medicine, which is now in its third edition (doctorgaby.com). He received his undergraduate degree from Yale University, his M.S. in biochemistry from Emory University, and his M.D. from the University of Maryland. He was in private practice for 19 years, specializing in nutritional medicine. Over the past 43 years, Dr. Gaby has developed a computerized database of more than 29,000 individually chosen medical journal articles related to the field of natural medicine. He was professor of nutrition and a member of the clinical faculty at Bastyr University in Kenmore, Washington, from 1995 to 2002.

He is past president of the American Holistic Medical Association and gave expert testimony to the White House Commission on Complementary and Alternative Medicine on the cost-effectiveness of nutritional supplements. He is the author of Preventing and Reversing Osteoporosis (Prima, 1994), The Doctor’s Guide to Vitamin B6 (Rodale Press, 1984), and co-author of The Patient’s Book of Natural Healing (Prima, 1999). He was Chief Science Editor for Aisle 7 (formerly Healthnotes, Inc.) and has appeared on the CBS Evening News and the Donahue Show.