A 34-year-old female presented with a long history of ocular allergies and perennial allergic rhinitis with seasonal exacerbations. She had been treated with oral, intranasal, and ophthalmic antihistamines and glucocorticoids, with varying degrees of success. She also had suffered from asthma since childhood and required frequent use of inhaled glucocorticoids and bronchodilators. Other symptoms included chronic fatigue, sensitivity to cold, waves of nausea with no relation to meals or time of day, difficulty with mental concentration, a general tendency to edema, waking up every night at 2 to 4 a.m. with difficulty falling asleep again, and recurrent palpitations. If she did not eat every 2 to 3 hours, she would develop a feeling of agitation, followed by severe fatigue. She also had an 8-year history of irregular menstrual periods, with cycles occurring approximately every 40 to 50 days. Numerous medications, nutritional supplements, and herbs had been tried for her symptoms, but the results had been for the most part unsatisfactory. Two weeks prior to her first visit, she had undergone extensive testing by an endocrinologist (including TSH and free T4), who had concluded that her endocrine system was normal.

On physical examination her Achilles tendon reflex return was delayed (suggestive of hypothyroidism) and her ankles and lower legs had an appearance of subtle myxedema. Her basal axillary temperature, which had been taken on 6 occasions prior to her first visit, ranged from 95.8 to 97.2 degrees F. On the basis of her symptoms, physical findings, and sub-normal body temperature (which presumably indicates a low basal metabolic rate), a provisional diagnosis of hypothyroidism was made. The patient advised to take 15 mg (1/4 grain) of Armour thyroid per day, increasing to 30 mg per day after 5 days, with a possible further increase, depending on her response and tolerance to the treatment. During the first two weeks, she experienced dramatic improvement in most of her symptoms. Around two months after the start of treatment, there was a recurrence of nausea and a decrease in her energy level. The dose of Armour thyroid was increased to 60 mg per day, and those symptoms again resolved. One month later, a further increase in dosage to 90 mg per day was necessary.

Of note, the patient’s asthma and rhinitis improved rapidly after the start of treatment, to the extent that she rarely needed medication for either condition anymore. At her most recent follow-up, ten months after the start of treatment, she rated the degree of improvement in her symptoms as follows (0% indicates no improvement, 100% indicates complete relief): fatigue and low energy (90%), nausea (90%), difficulty concentrating (95%), irregular menses (99%), asthma (85%), ocular allergies (80%; only seasonal exacerbations remained), palpitations (99%), edema (45%), and waking up at night (70%). Her need to eat every 2 to 3 hours had been extended to every 3 to 4 hours. Her sensitivity to the cold did not improve at all. No adverse side effects occurred and the pulse rate and blood pressure did not change.

Comment: This case illustrates two important points about which few in the medical community are aware: that hypothyroidism can cause allergic manifestations such as rhinitis and asthma, and that patients with clinical hypothyroidism frequently have normal blood tests for thyroid function. I have treated about 1,500 patients for "sub-laboratory hypothyroidism," and my experiences using thyroid hormone are described in the article cited below.

Gaby AR. "Sub-laboratory" hypothyroidism and the empirical use of Armour thyroid. Altern Med Rev. 2004;9:157-179.

A 38-year-old man had a long history of seasonal allergic rhinitis, occurring each spring and lasting about a month. Symptoms included nasal congestion, itchy eyes, and fatigue. During a symptomatic period, an intravenous infusion of 2.5 g of C, 600 mg of magnesium chloride, 1,000 mcg of vitamin B12, 100 mg of pyridoxine, 250 mg of pantothenic acid (dexpanthenol), and 1 ml of vitamin-B-complex-100 provided rapid relief. This treatment was repeated once a week or less often, as needed, during the hay-fever season and successfully controlled his symptoms. In subsequent years, he began the treatments shortly before, and repeated them periodically during, the hay fever season; this approach prevented the development of symptoms.

Comment: The treatment administered in this case was the "Myers cocktail" without the calcium. Several different components of this treatment have potential anti-allergy effects. For example, vitamin C at high concentrations destroys histamine and inhibits phosphodiesterase (an action similar to that of some asthma medications). Pyridoxine also inhibits phosphodiesterase, and niacinamide (present in the vitamin-B-complex-100) inhibited experimentally-induced anaphylactic shock and asthma in animals. The Myers cocktail has relieved allergy symptoms in about one-third to one-half of patients for whom it has been tried. This treatment is also beneficial for many patients with fatigue, fibromyalgia, migraine, asthma, and heart failure. Further information about the Myers cocktail is available in the article cited below.

Gaby AR. Intravenous nutrient therapy: the "Myers' cocktail". Altern Med Rev. 2002;7:389-403.

The mean serum concentration of bisphenol A (BPA) was significantly higher in 45 Japanese women (mean age, 32 years) with a history of 3 or more consecutive first-trimester miscarriages than in 32 age-matched healthy women with no history of live birth, infertility, or miscarriage (2.59 vs. 0.77 ng/ml; p = 0.024). The mean BPA concentration was nonsignificantly higher in recurrent-miscarriage patients who subsequently miscarried again than in those who subsequently had a successful pregnancy (4.39 vs. 1.22 ng/ml).

Comment: BPA is an endocrine disrupter with estrogenic activity. It is used as the monomer for the production of polycarbonate plastic products, which are used in the packaging, storing, and preparation of numerous foods and beverages, including water jugs, bottled beverages, baby food, and juice containers. BPA leaches out of such products at a rate that increases with repeated use. Food stored in cans that are lacquer-coated with a plastic lining may contain substantial amounts of BPA (4-23 mcg). Some vegetables (e.g., peas, artichokes, green beans, mixed vegetables, corn, and mushrooms) preserved in lacquer-coated cans, as well as the liquid in the cans, were found to have estrogenic activity, which was apparently due entirely to the presence of BPA. The results of the present study indicate that exposure to BPA is associated with recurrent miscarriage.

Sugiura-Ogasawara M, et al. Exposure to bisphenol A is associated with recurrent miscarriage. Hum Reprod. 2005;20:2325-2329.

Twenty-one hypercholesterolemic patients (mean age, 56 years) who were otherwise healthy received 20 mg/day of simvastatin for 6 months. The mean left ventricular ejection fraction (LVEF) decreased from 61% at baseline to 58% after one month (p = 0.02), but returned to the baseline value at three and six months. The authors concluded that simvastatin treatment is not associated with impairment in left ventricular function in hypercholesterolemic patients after 6 months of treatment. The study was funded by Merck Sharp and Dohme (Australia).

Comment: CoQ10 deficiency has been found in myocardial tissue of patients with congestive heart failure, and CoQ10 supplementation improved heart failure in some but not all studies. In the new study, the authors' conclusion did not mention the significant decrease in LVEF that occurred after 1 month of simvastatin treatment. This decrease could be clinically significant for patients with heart failure or marginal myocardial function. There are case reports in which initiation of treatment with a statin drug was followed by cardiac decompensation in patients with previously stable heart failure.

The authors of the new study reported that plasma CoQ10 levels decreased with simvastatin treatment, but that the ratio of CoQ10 to LDL cholesterol actually increased. One could argue that the ratio is more important than the absolute CoQ10 concentration, but neither of those measurements necessarily correlates closely with tissue CoQ10 concentrations. In animal studies, administration of lovastatin or pravastatin resulted in a significant reduction in CoQ10 concentrations in myocardial tissue.

One wonders whether statin-induced heart failure will be the next "Vioxx." Perhaps one day the main question in a class-action lawsuit will be what did the drug companies know and when did they know it regarding the potential of statins to cause heart failure and whether or not CoQ10 could prevent it.

Colquhoun DM, et al. Effects of simvastatin on blood lipids, vitamin E, coenzyme Q10 levels and left ventricular function in humans. Eur J Clin Invest. 2005;35:251-258.

Fifteen patients (median age, 36 years) with a chronic anal fissure were studied. Ten had been unsuccessfully treated by local application of isosorbide dinitrate, of whom 6 had experienced a severe headache during treatment. The patients applied 1 ml of a gel containing L-arginine (400 mg/ml) to the affected area five times a day for at least 12 weeks. If the fissure persisted, the treatment was continued for a total of 18 weeks. Thirteen patients completed the trial. After 12 weeks, complete healing was seen in three of 13 patients (23%) and after 18 weeks complete healing was seen in eight patients (62%). None of the 13 patients experienced typical nitric oxide-induced headache. Anal resting pressure decreased significantly, both after the first dose and after 12 weeks of treatment, compared with the baseline value (p < 0.005), and anodermal blood flow increased (p < 0.005) at each of these times. Seven patients experienced mild perianal skin irritation, which disappeared after they were given instructions regarding perianal hygiene and care.

Comment: Chronic anal fissure has a poor healing rate. It is associated with high anal resting pressure caused by overactivity of the internal anal sphincter. The increased tone of this muscle results in reduced anodermal blood blow, especially at the posterior midline. Local application of nitric oxide donors, such as isosorbide dinitrate and glyceryl trinitrate, promotes healing by reducing anal resting pressure and improving anodermal blood flow. However, these treatments cause headache in approximately 40% of patients. The results of the present study indicate that local application of L-arginine promotes healing of anal fissures, even in patients who have failed to respond to isosorbide dinitrate, without causing headache as a side effect.

Gosselink MP, et al. Treatment of chronic anal fissure by application of L-arginine gel: a phase II study in 15 patients. Dis Colon Rectum. 2005;48:832-837.

Two hundred thirty-eight residents of Linxian, China, with histologically confirmed mild or moderate esophageal squamous dysplasia (a precursor to esophageal cancer) were randomly assigned to receive, in double-blind fashion, 200 mcg/day of selenium (as selenomethionine), 200 mg twice a day of celecoxib, both, or placebo for 10 months, in a 2 x 2 factorial design. Esophagogastroduodenoscopy was performed before and after 10 months of treatment. Selenium treatment, as compared with no selenium, resulted in a trend toward increased dysplasia regression (43% vs. 32%) and decreased dysplasia progression (14% vs. 19%) (p = 0.08 for the combined endpoint). In unplanned stratified analysis, compared with no selenium, selenium favorably affected the change in dysplasia grade among 115 subjects with mild dysplasia at baseline (39% vs. 21% for regression, 19% vs. 36% for progression; p = 0.02 for the combined endpoint), but not among 123 subjects with moderate dysplasia at baseline (p = 1.00).

Comment: This study suggests that selenium has a protective effect on disease progression in people with mild, but not moderate, esophageal squamous dysplasia. The results should be interpreted with caution, because they were obtained in a post-hoc stratified analysis, which is less reliable than a pre-planned analysis. Nevertheless, the results are consistent with many other studies showing an anticancer effect of selenium. Selenium prophylaxis would be expected to be most effective when begun early in the course of the disease; for example, at the time someone is offered his or her first cigarette or boiling hot cup of tea.

Limburg PJ, et al. Randomized, placebo-controlled, esophageal squamous cell cancer chemoprevention trial of selenomethionine and celecoxib. Gastroenterology. 2005;129:863-873.

The Vitamin Intervention for Stroke Prevention (VISP) trial did not show efficacy of high-dose vitamin therapy (2.5 mg of folic acid, 25 mg of pyridoxine, and 400 mcg of vitamin B12 daily) as compared with low-dose vitamin therapy (20 mcg of folic acid, 200 mcg of vitamin B6, and 6 mcg of vitamin B12 daily) with respect to recurrent vascular events in patients with a history of a stroke.

In a new study, the data from the VISP trial were re-analyzed, after exclusion of patients with low and very high vitamin B12 levels at baseline (< 250 and > 637 pmol/L, representing the 25th and 95th percentiles). Patients with very low vitamin B12 levels (< 150 pmol/L) in both study arms were receiving parenteral vitamin B12 injections outside of the study, and those with moderately low levels may have been vitamin B12 malabsorbers, and therefore less likely to benefit from oral supplementation. Patients below the tenth percentile of renal function were also excluded. The criteria for this subgroup were defined before any data analysis. In all, 59% of the initial study group was included in the subgroup analysis. For the combined end point of ischemic stroke, coronary disease, or death, there was a 21% reduction in the risk of events in the high-dose group compared with the low-dose group (unadjusted p = 0.049; adjusted for age, sex, blood pressure, smoking, and vitamin B12 level, p = 0.056).

Comment: The results of this study suggest that relatively large doses of vitamin B12 may be necessary for some patients to maximize the benefits of B-vitamin therapy with respect to cardiovascular disease prevention. The failure to use large doses of vitamin B12 in some homocysteine-lowering trials might explain the conflicting results obtained in these studies. Patients with chronic renal failure on hemodialysis are known to require frequent parenteral doses of vitamin B12 in order to achieve the maximum homocysteine-lowering effect. Perhaps some patients with cardiovascular disease also have a higher-than-normal requirement for vitamin B12.

Spence JD, et al. Vitamin Intervention For Stroke Prevention trial: an efficacy analysis. Stroke. 2005;36:2404-2409.

Two hundred-ninety women (aged 21 to 38 years) with low-risk pregnancies were randomly assigned to continue their usual diet (control group) or to adopt a cholesterol-lowering diet (intervention group) that promoted fish, low-fat meats and dairy products, oils, whole grains, fruits, vegetables, and legumes from gestational week 17-20 until delivery. Maternal total- and LDL-cholesterol levels were lower in the intervention group than in the control group (p < 0.01), but lipid levels were similar in the neonates from the two groups. The incidence of premature delivery (< 37 weeks) was 0.7% in the intervention group and 7.4% in the control group (relative risk = 0.10; 95% confidence interval, 0.01-0.77). The incidence of other pregnancy complications was similar in the two groups. The authors concluded that consumption of a cholesterol-lowering diet reduced the incidence of preterm delivery in women with low-risk pregnancies.

Comment: The diet used in this study contained a wide variety of healthful foods. The fact that it was a cholesterol-lowering diet may not be relevant to its beneficial effect on pregnancy outcome. Perhaps the correct conclusion is that a diet containing high-quality macronutrients and abundant amounts of micronutrients favorably influences pregnancy outcome. Eggs are high in cholesterol, but they also contain high-quality protein and a large amount of choline, a nutrient that is crucial for fetal and infant brain development. The results of the new study should not lead to the conclusion that pregnant women should avoid eating eggs.

Khoury J, et al. Effect of a cholesterol-lowering diet on maternal, cord, and neonatal lipids, and pregnancy outcome: a randomized clinical trial. Am J Obstet Gynecol. 2005;193:1292-1301.