Alan R. Gaby, MD
Iron Deficiency Is Very Common Among Young US Females
Serum ferritin levels were measured in 3,490 nonpregnant females (aged 12-21 years) participating in the National Health and Nutrition Examination Surveys in 2003-2010 and 2015-2020. The overall prevalence of iron deficiency (defined, according to the World Health Organization, as a serum ferritin level < 25 µg/L) was 38.6%. The prevalence was 17% using a ferritin cutoff level of 15 µg/L, and 77.5% using a ferritin cutoff level of 50 µg/L. Among premenarchal individuals (5.4% of the study participants) the prevalence of iron deficiency was 27.1% using a ferritin cutoff level of 25 µg/L. The overall prevalence of iron-deficiency anemia (hemoglobin < 12 g/dl and ferritin < 25 µg/L) was 6.3%.
Comment: This study found that iron deficiency is extremely common among young US females. The high prevalence of iron deficiency can be attributed in part to menstrual blood loss, but iron deficiency was also common (27.1%) among girls who had not started menstruating. Iron deficiency can be an important health problem, even in the absence of anemia. Studies have shown that, in people with iron deficiency without anemia, iron supplementation improves exercise performance and decreases fatigue. In addition, iron deficiency can cause or exacerbate symptoms such as anxiety, depression, and difficulty with mental concentration. Most of the iron-deficient participants in this study were not anemic, so the presence of a normal blood count does not rule out iron deficiency. A serum ferritin level or other laboratory measure of iron status should be included as part of an overall health evaluation in young US females.
There is a difference of opinion among doctors and researchers regarding what serum ferritin level warrants iron supplementation. According to some studies, patients with a level below 50 µg/L stand to benefit from extra iron. Iron supplementation of non-deficient patients is not risk-free; it may increase the incidence of cardiovascular disease and some other chronic illnesses, and it can harm people who carry an iron-overload gene. Therefore, iron treatment should be reserved primarily for patients with documented iron deficiency or borderline-low iron status.
Weyand AC, et al. Prevalence of iron deficiency and iron-deficiency anemia in US females aged 12-21 years, 2003-2020. JAMA. 2023;329:2191-2193.
Garlic/Onion Extract Prevents Respiratory Infections
Sixty-five elderly nursing home residents (mean age, 84 years) in Spain were randomly assigned to receive, in double-blind fashion, a single daily dose of an extract of garlic and onion or placebo for 36 weeks. The extract contained 14 mg of garlic powder and 86 mg of concentrated onion extract. The odor of the extract was masked to maintain blinding. The incidences of the common cold and of influenza were each significantly lower in the garlic/onion group than in the placebo group.
Comment: Garlic has demonstrated activity against a wide range of bacteria and also against various viruses and fungi. Onion extracts have also exhibited antimicrobial activity in several studies. The results of the present study indicate that administration of a garlic/onion extract decreased the incidence of respiratory infections in elderly nursing home residents. The inclusion of garlic and onion in the diet or in supplement form should therefore be considered as a component of an overall infection-preventing strategy for elderly individuals, as well as for others who tend to be susceptible to developing infections.
Garcia-Garcia J, et al. Beneficial effects of daily consumption of garlic and onion extract concentrate on infectious respiratory diseases in elderly resident volunteers. Nutrients. 2023;15:2308.
Curcumin Effective for Functional Dyspepsia
Two hundred-six Thai patients (mean age, 49.7 years) with functional dyspepsia were randomly assigned to receive, in double-blind fashion, curcumin (500 mg 4 times a day), omeprazole (20 mg once a day), or both treatments for 28 days. One hundred fifty-one patients completed the study. Significant improvements were seen in the mean Severity of Dyspepsia Assessment score in all 3 groups, with no significant difference between groups.
Comment: Functional dyspepsia (also called non-ulcer dyspepsia or indigestion) is one of the most common gastrointestinal conditions. Symptoms are often provoked by eating, and include epigastric pain or heartburn, belching, nausea, abdominal bloating, and a sensation of abdominal fullness after eating a small amount of food. Dyspepsia is associated with various gastrointestinal diseases and with other conditions such as diabetes and hypothyroidism. It also occurs as a side effect of certain medications. A large proportion of cases are idiopathic.
Proton pump inhibitors have been shown in a number of studies to relieve symptoms of functional dyspepsia. In the present study, curcumin and omeprazole had comparable efficacy in the treatment of functional dyspepsia. The combination of curcumin and omeprazole did not appear to be more effective than either treatment alone. Long-term use of proton pump inhibitors may cause various nutritional deficiencies, and also has been associated with an increased risk of developing infections, osteoporosis, gastric cancer, food allergies, and chronic kidney disease. Curcumin may therefore be a safer alternative for many patients with functional dyspepsia.
A potential downside to curcumin is that it may contain substantial amounts of oxalate, and therefore may increase the risk of kidney stones in susceptible individuals. Curcumin is extracted from the spice, turmeric, which is said to contain high concentrations of oxalate. Some manufacturers claim that their extraction process removes nearly all of the oxalate from the final product. Individuals who need to restrict their oxalate intake should use curcumin products that are certified to have low oxalate content.
Kongkam P, et al. Curcumin and proton pump inhibitors for functional dyspepsia: a randomised, double blind controlled trial. BMJ Evid Based Med. 2023;28:399-406..
Is Curcumin Effective Against Osteoarthritis?
One hundred one Australian adults (mean age, 59 years) with osteoarthritis of the knee were randomly assigned to receive, in double-blind fashion, 500 mg of an extract of turmeric (standardized to contain 50% curcuminoids) twice a day or placebo for 8 weeks. Mean pain severity, as determined by the Knee Injury and Osteoarthritis Outcome score, improved by 20% in the turmeric group and by 9% in the placebo group (p < 0.01 for the difference in the change between groups). Compared with placebo, turmeric also resulted in a significant increase in the distance walked on the 6-minute walk test.
Comment: Curcumin, a compound present in the spice, turmeric, has both anti-inflammatory activity and pain-relieving effects. In the present study, administration of curcuminoids (a combination of curcumin and curcumin derivatives) decreased pain and improved functional capacity in patients with osteoarthritis of the knee. The study was funded by Dolcas Biotech, which manufactures the turmeric product used in the study, and which played a role in the design of the study and in the writing of the manuscript. In addition, one of the study authors was employed by Dolcas Biotech. The results of the study should therefore be interpreted with caution.
A meta-analysis of 8 randomized clinical trials (3 from Thailand, 2 from India, 1 each from Iran, Italy, and Japan) provided support for a beneficial effect of curcumin in the treatment of osteoarthritis. However, the authors of the meta-analysis concluded that the methodological quality of the studies was not sufficient to draw definitive conclusions.[1]
Based on the available evidence, one can conclude that turmeric and curcumin are possibly effective against osteoarthritis, but that additional studies are needed. Precautions regarding the use of curcumin products are discussed in the preceding entry.
Lopresti AL, et al. An investigation into the effects of a curcumin extract (Curcugen®) on osteoarthritis pain of the knee: a randomised, double-blind, placebo-controlled study. Nutrients. 2022;14:41.
Hypothyroidism and Migraines
Eighty-seven adults (mean age, 34 years) living in India who were experiencing episodic migraines and who had subclinical hypothyroidism (defined as a TSH level of 4.5-10.0 mIU/L and a normal free-T4 level) were randomly assigned to receive (method of blinding not clear) 25 µ per day of levothyroxine or placebo for 3 months. After 3 months, the mean frequency of headaches was 49% lower (p = 0.001), mean headache severity was 36% lower (p = 0.001), and the mean Migraine Disability Assessment Score was 19% lower (better) (p < 0.03) in the levothyroxine group than in the placebo group.
Comment: In migraine patients with overt hypothyroidism, treatment of the hypothyroidism is known to improve headaches. The results of the present study suggest that thyroid hormone-replacement therapy may also benefit migraine sufferers who have subtle (subclinical) hypothyroidism.
In my experience, laboratory tests for thyroid function are frequently normal in patients with clinical evidence of hypothyroidism, and an empirical trial of thyroid hormone relieves a wide array of symptoms in many such patients.[2] [3] A clinical trial of thyroid hormone could therefore be considered for migraine sufferers who have clinical evidence of hypothyroidism, even if their laboratory tests are normal.
Dev P, et al. The effect of low dose thyroid replacement therapy in patients with episodic migraine and subclinical hypothyroidism: A randomised placebo-controlled trial. Cephalalgia. 2023;43:3331024231182684.
Can Cocoa Flavanols Prevent Cardiovascular Disease?
US adults (n = 21,442; aged 60 years or older for men and 65 years or older for women) who were free of major cardiovascular disease were randomly assigned to receive, in double-blind fashion, 2 capsules per day of a cocoa extract (providing 500 mg per day of flavanols), a multivitamin, both treatments, or placebo for a median duration of 3.6 years. The present paper reported the results of the cocoa extract arm of the trial. In an analysis that included only those participants who completed the trial and took at least 75% of the study pills, the incidence of total cardiovascular events (a composite of myocardial infarction, stroke, coronary revascularization, cardiovascular death, carotid artery disease, peripheral artery surgery, and unstable angina) was significantly lower by 15% in the cocoa group than in the placebo group. No significant adverse effects were reported.
Comment: Cocoa contains a subclass of polyphenols known as flavanols, which have been shown in short-term trials to have a favorable effect on cardiovascular risk factors. In the present study, daily consumption of cocoa flavanols for a median of 3.6 years reduced the incidence of cardiovascular events among elderly individuals who were free of major cardiovascular disease at baseline. One would have to consume a large amount of cocoa powder or dark chocolate to obtain 500 mg per day of flavanols. However, supplements that provide cocoa flavanols in concentrated form are commercially available.
Sesso HD, et al. Effect of cocoa flavanol supplementation for the prevention of cardiovascular disease events: the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial. Am J Clin Nutr. 2022;115:1490-1500.
Ubiquinol and D-Ribose for Heart Failure
One hundred fifty-three patients (aged 50 years or older) with heart failure with preserved ejection fraction (HFpEF; defined as a left ventricular ejection fraction of 50% or higher) were randomly assigned to receive, in double-blind fashion, 600 mg per day of ubiquinol, 15 g per day of D-ribose powder, both treatments, or placebo for 12 weeks. Compared with placebo, each treatment and the combination treatment produced significant improvements in the Kansas City Cardiomyopathy Questionnaire clinical summary score, level of vigor (as determined by a subscale of the Profile of Mood States), left ventricular ejection fraction, B-type natriuretic peptides, and blood level of ATP. Neither treatment increased the walking distance on the 6-minute walk test compared with placebo. Combination therapy was not more effective than ubiquinol or D-ribose alone.
Comment: Most research on the treatment of heart failure has enrolled patients with a decreased left ventricular ejection fraction (also known as systolic heart failure). Although as many as 50% of heart failure patients may have HFpEF (also known as diastolic heart failure), there has been much less research on the treatment of this type of heart failure. Numerous studies have demonstrated that coenzyme Q10 (in the form of ubiquinone) is beneficial for patients with systolic heart failure, although in some studies the results were negative. Preliminary evidence suggests that ubiquinol (the reduced form of coenzyme Q10) is also effective for systolic heart failure, and may be even more effective than ubiquinone in some cases. The results of the present study suggest that ubiquinol may also be useful for patients with HFpEF.
The rationale for using ribose to treat HFpEF is that in heart failure there may be a decrease in myocardial concentrations of ATP and an associated suppression of diastolic function. Ribose has been shown in animal studies to increase myocardial ATP levels and to improve diastolic function.
Based on the results of the present study, ubiquinol and/or D-ribose may be considered for adjunctive treatment of heart failure with preserved ejection.
Pierce JD, et al. Effects of ubiquinol and/or D-ribose in patients with heart failure with preserved ejection fraction. Am J Cardiol.2022;176:79-88.
Alginate “Raft Therapy” for Laryngopharyngeal Reflux
Fifty Italian patients with laryngopharyngeal reflux were randomly assigned to receive a proton pump inhibitor (PPI; 20 mg of omeprazole once a day) or Gastrotuss (20 ml 3 times a day) for 2 months. Gastrotuss contains magnesium alginate and simethicone (an antifoaming agent used to treat symptoms caused by excessive gas). Symptoms related to reflux improved significantly in both groups, with no significant difference between groups.
Comment: Laryngopharyngeal reflux differs from gastroesophageal reflux disease (GERD) in that patients have daytime (upright) reflux without heartburn or esophagitis. Injury to the larynx can occur as a result of the action of acid and pepsin on the laryngeal tissue. Treatment of laryngopharyngeal reflux may include PPIs and avoidance of acidic foods.
Alginate is a compound derived from seaweed. It interacts with gastric acid within a few minutes and forms a viscous gel that floats on top of the gastric contents like a raft and physically inhibits the reflux of gastric contents into the esophagus. In clinical trials, sodium alginate was at least as effective as an antacid or a PPI in patients with symptomatic GERD. In patients with GERD who continued to have reflux symptoms despite PPI treatment, adding sodium alginate significantly decreased symptoms. The present study suggests that alginate (in the form of magnesium alginate) may also be beneficial in the treatment of laryngopharyngeal reflux.
Pizzorni N, al. Magnesium alginate versus proton pump inhibitors for the treatment of laryngopharyngeal reflux: a non-inferiority randomized controlled trial. Eur Arch Otorhinolaryngol. 2022;279:2533-2542.
References
[1]. Daily JW, et al. Efficacy or turmeric extracts and curcumin for alleviating the symptoms of joint arthritis: a systematic review and meta-analysis of randomized clinical trials. J Med Food. 2016;19:717-729)
[2]. Gaby AR. Hypothyroidism. In Gaby AR. Nutritional Medicine, Third Edition. Concord, NH, 2023, www.doctorgaby.com, chapter 8.
[3]. Gaby AR. “Sub-laboratory” hypothyroidism and the empirical use of Armour Thyroid. Altern Med Rev. 2004;9(2):157-179.
Published February 24, 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.