Some 3,994 patients aged 55 years or older with vascular disease or diabetes were randomly assigned to receive, in double-blind fashion, 400 IU/day of vitamin E (RRR-alpha-tocopheryl acetate) or placebo for a median of 7.0 years. The incidence of heart failure was 19% higher (14.7% vs. 12.6%; p = 0.007) and the incidence of hospitalization for heart failure was 40% higher (5.8% vs. 4.2%; p = 0.002) in the vitamin E group than in the placebo group. Cardiovascular mortality did not differ significantly between groups. The authors concluded that, in patients with vascular disease or diabetes, long-term supplementation with 400 IU/day of vitamin E may increase the risk for heart failure.

Comment: Virtually all of the clinical research on vitamin E has used alpha-tocopherol, which is only one of the four forms of vitamin E that occur naturally in food (alpha-, beta-, gamma-, and delta-tocopherol). While early research suggested that most of the biological activity of vitamin E resides in the alpha- fraction, it is now known that one of the other components – gamma-tocopherol ¬– has important functions, at least one of which is relevant to the issue of congestive heart failure. Furthermore, treatment with large doses of alpha-tocopherol has been shown to deplete gamma-tocopherol, thereby upsetting the natural balance of vitamin E isomers in the body.

Gamma-tocopherol is metabolized largely to 2,7,8-trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman (gamma-CEHC), a compound that appears to function as a "natriuretic hormone." It has long been known that mammals respond to sodium-induced plasma-volume expansion with a combination of sustained natriuresis (urinary sodium excretion), inhibition of sodium transport, and increased vasoreactivity. It has been assumed that these effects are due to the release of a "natriuretic hormone," but for many years scientists were unable to find an endogenous compound that exerted all of these actions. In 1996, researchers identified gamma-CEHC as such as substance and subsequently found it to be a metabolite of gamma-tocopherol (J Pharmacol Exp Ther 1997;282:657-662). In that respect, gamma-tocopherol might be considered a "pro-hormone," a compound that helps regulate extracellular fluid and sodium balance, which is one factor involved in the pathogenesis of congestive heart failure. It is possible that, for some people, alpha-tocopherol-induced gamma-tocopherol deficiency would lead to impaired regulation of sodium and water balance, thereby increasing the stress that every salty meal or snack would place on the heart.

Alpha-tocopherol has a number of properties that might make it useful as a cardioprotective nutrient. It inhibits platelet aggregation, inhibits the oxidation of LDL cholesterol, prevents the development of atherosclerosis in experimental animals, and reduces the deleterious effects of hypoxia in both animals and humans. Clinical trials have also shown it to be an effective treatment for intermittent claudication and for preventing postoperative thromboembolism. However, whatever beneficial effects alpha-tocopherol has on cardiac health might be counterbalanced by a reduction of gamma-tocopherol levels in the body, a reduction that would presumably be more pronounced when using higher doses of alpha-tocopherol.

While high-dose alpha-tocopherol may have a negative effect in certain groups of susceptible people, the same may not be true of "mixed tocopherols," which is a mixture of the four naturally occurring forms of vitamin E. Approximately 70% of the vitamin E in food is in the form of gamma-tocopherol. Most of the vitamin E supplements on the market, on the other hand, contain only alpha-tocopherol, although mixed tocopherols are commercially available. People who supplement with mixed tocopherols would presumably derive the benefits of both alpha- and gamma-tocopherol, without creating an imbalance in these two forms of vitamin E. While it may be many years before the alpha-tocopherol research is repeated using mixed tocopherols, I predict that a combination of the four naturally occurring tocopherols will eventually be shown to effective both for preventing and treating heart disease. It may even turn out that relatively small doses of mixed tocopherols are effective, if used as part of a comprehensive nutritional and lifestyle program.

Lonn E, et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA 2005;293:1338-1347.

Thirty dental students and auxiliary personnel (aged 21-32 years) were randomly assigned, in double-blind fashion, to rinse their mouths for 5 minutes twice a day with 5 ml (1 teaspoon) of either a 0.1% folic acid solution or placebo solution. After 60 days of treatment, gingival inflammation, as assessed by the gingival index and bleeding index, was significantly less in the folic acid group than in the placebo group.

Comment: Several studies have shown that folic acid supplementation can improve gingivitis. Topical application of folic acid, as in a mouth rinse, has been found to be more effective than oral ingestion of a similar amount of the vitamin. It has been suggested that a localized deficiency of folic acid plays a role in the development of gingivitis, and that this deficiency can be corrected by bathing the gingival tissues in folic acid.

Folic acid has also been used to treat phenytoin (dilantin)-induced gingival hyperplasia. Although this treatment may improve gum health, it should be used with caution, because large doses of folic acid (more than 1 mg/day) have the potential to interfere with the anticonvulsant effect of phenytoin. On the other hand, treatment with phenytoin frequently causes folic acid deficiency, so people taking this drug should receive at least a modest dose of supplemental folic acid.

Vogel RI, et al. The effect of topical application of folic acid on gingival health. J Oral Med 1978;33:20-22.

Ten patients with recurrent oral aphthous ulcers (canker sores) were randomly assigned, in double-blind fashion, to use one of two different toothpastes for three months, and then the alternate toothpaste for an additional three months. The toothpastes differed only in their content of sodium lauryl sulfate (SLS), a commonly used detergent. One of the toothpastes contained 1.2% SLS and the other contained none. The number of new aphthous ulcers that occurred was 64% less with the SLS-free toothpaste than with the SLS-containing toothpaste (p < 0.05).

Comment: Recurrent aphthous ulceration is a common, painful condition of the oral cavity. In many cases, recurrences can be prevented by identifying and avoiding allergenic foods, of which wheat appears to be the most frequent offender. Some patients with aphthous ulcers have deficiencies of iron, zinc, folic acid, or vitamin B12, and correction of these deficiencies may prevent recurrences.

SLS is added to most commercially available toothpastes as a cleaning agent. While it is effective for cleaning the teeth, it may also denature the mucin layer that coats and protects the tissues of the oral cavity, thereby exposing the underlying epithelium and rendering it more vulnerable to exogenous irritants and allergens. While SLS-free toothpastes are hard to find, most health food stores stock one or two acceptable products.

Herlofson BB, Barkvoll P. Sodium lauryl sulfate and recurrent aphthous ulcers. Acta Odontol Scand 1994;52:257-259.

Of approximately 65 patients with treatment-refractory acne-like perioral dermatitis, all had been using toothpaste containing fluoride. When these patients were switched to non-fluoridated toothpaste, about half had a clearance of their lesions within two to four weeks. The non-responders then switched from their present toothpaste, which contained brightening and flavoring agents and other unknown chemicals, to baking soda and a commercially available mouthwash after brushing. Nearly all of these patients had almost complete clearing of their lesions. Patients who resumed fluoride toothpaste invariably developed a recurrence of the dermatitis. Of patients who were able to recall, all stated that the side on which they had the most severe dermatitis was the side on which they generally slept. That observation supports the hypothesis that nocturnal salivary drainage of chemicals onto the involved areas of skin exacerbates the lesions.

Comment: Perioral dermatitis affects up to 1% of the population, and is more prevalent among women than among men. It is characterized by chronic papulopustular lesions around the mouth that resemble rosacea. Perioral dermatitis was first described in 1957, around the time that fluoridated toothpaste was introduced in the United States. In 1967, the German literature described perioral dermatitis as a "new entity." The delayed recognition of this condition in Germany may have been related to the later marketing of fluoridated toothpaste in that country. The results of the present study suggest that sensitivity to fluoride or to other ingredients in toothpaste is the most important cause of perioral dermatitis.

Saunders MA Jr. Fluoride toothpastes: a cause of acne-like eruptions. Arch Dermatol 1975;111:793.

One hundred ninety-five women with high salivary levels of Streptococcus mutans (the bacterium associated with dental caries) were randomly assigned to chew xylitol gum (n = 120), or to receive treatment with chlorhexidine varnish (n = 32) or fluoride (n = 36). The women started using xylitol chewing gum three months after the birth of a baby and continued it until the child was two old. The chewing gum contained 65% (w/w) xylitol; the average frequency of consumption was four times a day, providing a daily xylitol dose of 6 to 7 g. The children did not receive any prophylactic measures against caries before the age of 2 years. Compared with the other treatments, maternal use of xylitol gum significantly reduced S. mutans colonization in the children's teeth at two years of age. At five years of age, the prevalence of dental caries was 70% lower in the xylitol group than in the other two groups. In all groups, the presence of S. mutans colonization in children at the age of two years was significantly related to each child’s age at the first development of caries.

Comment: The results of this study indicate that maternal use of xylitol chewing gum during the first two years of their child’s life (starting at age three months) can reduce the incidence of dental caries in the children, presumably by preventing the transmission of S. mutans from mother to child. Other studies have shown that children old enough to chew gum can reduce the incidence of dental caries by 30-80%, if they chew xylitol gum regularly. The protective effect of xylitol appears to be more pronounced for teeth that erupt after gum chewing has started than for teeth that are already present.

Isokangas P, et al. Occurrence of dental decay in children after maternal consumption of xylitol chewing gum, a follow-up from 0 to 5 years of age. J Dent Res 2000;79:1885-1889.

Strontium is present in bones and teeth and is thought to replace a small fraction of the calcium in the hydroxyapatite crystal during mineralization. Epidemiologic studies have shown that the incidence of caries in areas with optimal fluoridation is related to the level of strontium in the water. The lowest incidence of caries occurred in areas with strontium levels of 5.4 and 8.3 mg/L, with increased incidence at higher and lower levels of water strontium. Strontium supplementation has also reduced the incidence of experimentally induced caries in animals.

Comment: Interest in strontium has been revived recently, after a three-year study demonstrated that large doses of the mineral (680 mg per day) increased bone mineral density and reduced the incidence of fractures in postmenopausal women. However, that dose of strontium is 200 to 300 times the amount normally present in food, and well above the amount that epidemiological studies suggest is optimal for caries prevention. In animal studies, administration of large doses of strontium caused bone mineralization defects and inhibited the synthesis of 1,25-dihydroxyvitamin D (the active form of vitamin D. While no abnormalities of bone mineralization occurred in the three-year human study, one cannot rule out the possibility that longer-term use of pharmacological doses would adversely affect bone or tooth structure.

A typical diet provides about 2 to 3 mg of strontium per day, and epidemiological studies suggest that doubling that amount might help prevent dental caries. Foods high in strontium include fish, whole grains, kale, parsley, lettuce, Brazil nuts, and molasses. More than 95% of the strontium is lost when sugar cane or beets are refined into white sugar. Most of the strontium is lost when whole wheat is refined to white flour.

Anonymous. Strontium and dental caries. Nutr Rev 1983;41:342-344.

Thirty-eight healthy Japanese men (aged 24-46 years) whose body weight was normal to overweight were divided into two groups with similar body mass index (BMI) and waist circumference distributions. The groups were assigned to consume, in double-blind fashion, 340 ml/day of one of two different oolong tea beverages for 12 weeks. One beverage provided 690 mg/day of catechins and the other provided 22 mg/day. The catechin content of the tea was adjusted by adding different amounts of catechins extracted from green tea. At the end of the treatment period, body weight, BMI, waist circumference, body fat mass, and subcutaneous fat area were significantly lower in the group receiving the higher dose of catechins than in the group receiving the lower dose.

Comment: These results suggest that daily consumption of green tea catechins can reduce body fat. Previous research has shown that green tea catechins stimulate thermogenesis (i.e., increase the amount of calories burned) of peripheral tissue in vitro. In a study of healthy men, administration of a green tea extract increased 24-hour energy expenditure by 4% relative to placebo (p < 0.001). Unlike various stimulant drugs used to promote weight loss, the green tea extract did not increase heart rate. In a study of moderately obese people (Phytomedicine 2002;9:3-8), administration of a green tea extract daily for 12 weeks resulted in a mean weight loss of 4.6% and a mean reduction in waist circumference of 4.5% (it was not stated in that study whether dietary modifications were made).

These studies suggest that supplementation with green tea catechins may help people lose weight and body fat. While long-term studies are needed to determine the safety of this treatment, green tea catechins are almost certainly safer than stimulant drugs, and may even help prevent cancer.

Nagao T, et al. Ingestion of a tea rich in catechins leads to a reduction in body fat and malondialdehyde-modified LDL in men. Am J Clin Nutr 2005;81:122-129.

Thirty-nine healthy men and women supplemented their usual diet with 60 mmol of potassium chloride (about 2.3 g of potassium) per 70 kg of body weight per day for 3 days, while 35 others maintained their usual potassium intake. Potassium supplementation significantly decreased platelet reactivity, as determined by an increase in the concentration of ADP needed to produce 50% of the maximal initial rate of platelet aggregation.

Comment: High potassium intake has been shown to reduce blood pressure in people with hypertension. In addition, observational studies have found that increasing potassium intake is associated with lower risk of stroke, even after adjustment for blood pressure. Thus, potassium may help prevent stroke both by lowering blood pressure and by another, as yet unidentified, mechanism. Drugs that inhibit platelet aggregation, such as aspirin and clopidogrel bisulfate (Plavix) are known to reduce the risk of stroke, so it is possible that inhibition of platelet aggregation is the other mechanism by which potassium prevent strokes. Good food sources of potassium include fruits (particularly bananas and oranges), vegetables, legumes, and potatoes (with the skin).

Kimura M, et al. Potassium chloride supplementation diminishes platelet reactivity in humans. Hypertension 2004;44:969-973.