Description

Boron, the fifth chemical element, is a dietary trace mineral found primarily in plant foods. It is essential for plant growth. Recently it has been shown to be essential in an animal species (zebra fish), and evidence is mounting that boron is probably essential for humans, as well. The first edition of The Merck Manual (1899) credits boric acid, the most common form of boron, with being a useful treatment for amenorrhea, dysmenorrhea, epilepsy and elevated uric acid. Boric acid has, in fact, proved to be ineffective for all of those disorders, but recent research lends some preliminary support for the use of boron for the promotion of bone and joint health. There is less evidence that it may be helpful in enhancing mental cognition.

Actions & Pharmacology

Actions

Boron may have estrogen-mimetic and anti-osteoporotic activity. It may also participate in regulating the respiratory burst of neutrophils.

Mechanism of Action

The biochemical mechanism of boron is not yet known. Currently, two hypotheses have been advanced for the biochemical function of boron in animals, including humans. The first is that boron plays a role in cell-membrane functions that influence response to hormone action, trans-membrane signaling and trans-membrane movement of regulatory ions. Boron has been shown, in animal models, to influence the transport of extracellular calcium and the release of intracellular calcium in platelets activated by thrombin. It also influences redox actions involved in cellular membrane transport in plants.

A second hypothesis is that boron acts as a metabolic regulator in several enzymatic systems. Boron may play an important role in regulating the respiratory burst, which is the reactive-oxygen-species mechanism by which white blood cells kill micro-organisms. If boron does in fact regulate the respiratory burst, it assumes the role of a novel antioxidant, preventing some of the collateral damage that may occur when reactive oxygen species react with surrounding tissue.

The biochemistry of boron is essentially that of boric acid. Boric acid forms complexes with many of the chemical substances found in the body, such as carbohydrates (sugars and polysaccharides), nucleotides (such as adenosine monophosphate and niacinamide adenine dinucleotide) and vitamins (such as ascorbic acid, pyridoxine and riboflavin). Boric acid forms esters with hydroxyl groups found in many of these compounds. This occurs preferentially when the hydroxyl groups are next to each other and on the same side of the molecules. The most stable esters are those in which boric acid is the bridge between two carbohydrate molecules, e.g. fructose-boron-fructose. Such soluble boron complexes are found naturally in phloem saps and nectars in plants. Polysaccharides containing boron in similar linkages are found in plant cell walls in the form of pectins.

Pharmacokinetics

Nutritional forms of boron are readily and completely absorbed. They are either rapidly converted to boric acid and are absorbed as such or they are converted to boric acid following absorption. Absorbed boric acid is rapidly distributed throughout body water by passive diffusion. After being absorbed, boron's ratio of blood-to-soft-tissue concentration is approximately one. Concentrations of boron in bone, teeth and fingernails exceed those in blood by about a factor of four. Certain nutritional forms of boron (e.g., boron carbohydrate esters) are metabolized to boric acid. Boric acid itself does not undergo metabolism. It is eliminated unchanged in the urine. The half-life for elimination of boric acid, whether administered orally or intravenously, is about 21 hours.

Indications & Usage

Boron may be indicated for the promotion of bone and joint health, particularly in women. There is less evidence to support claims that boron enhances cognition and ameliorates the symptoms of arthritis. There is no evidence that it promotes the development of lean muscle mass. The evidence that boron may protect against prostate cancer is conflicting.

Overdosage

The lowest levels at which boron supplementation may be toxic have not been established. In 1904, human volunteers consuming greater than 500 mg of boric acid daily (this is equivalent to about 180 mg of elemental boron) showed symptoms of poor appetite and digestive problems. Symptoms of acute toxicity typically include nausea, diarrhea and abdominal cramps. The symptoms of chronic toxicity include nausea, poor appetite and weight loss.

Dosage

Except for tolerable upper intake levels (UL—see table), no DRI (dietary reference intake) has yet been established for boron. However, since there is some evidence for the essentiality of boron in humans, a DRI is likely to be established in the future. The DRI that is likely to be established for boron will probably be an AI (adequate intake) rather than an RDA (recommended dietary allowance).

Fruits and vegetables are the most important dietary sources of boron. A vegetarian diet is higher in boron than the typical American diet. The range of intake in the American diet is 0.5 to 3 mg daily. The average intake is about 1 mg daily. It is lower in the elderly. There is some evidence that this average intake may be too low; a more optimal intake of boron may be 2 to 3 mg daily.

Dietary supplements of boron now available include the following forms: sodium borate, boron citrate, boron aspartate, boron glycinate, calcium fructoborate. Once ingested, all of these forms are rapidly converted in the body to boric acid. Natural plant forms of boron or similar synthetic forms are not yet available, and whether they will have greater health benefits than the currently marketed forms remains to be seen.

Boron is often sold in supplements that combine a variety of nutrients. For example, it is found in products for bone and joint health that often combine such nutrients as vitamin D, calcium, magnesium, soy isoflavones, chondroitin sulfate, glucosamine, curcumin, boswellia, gelatin, ipriflavone, SAMe and others (see monographs on these substances). There's no evidence yet available that the therapeutic effects of boron are increased by such combinations.

The Food and Nutrition Board of the U.S. National Academy of Sciences has published the following Dietary Reference Intakes (DRI) for boron. A summary of DRIs for various age groups is as follows:

Literature

Research & Summary

Boron's potential therapeutic value in promoting bone and joint health is underscored by the widespread incidence of osteoporosis. There are more than 100 million afflicted by this disease worldwide, eight million of them in the United States. Postmenopausal women are mostly affected, but osteoporosis is also found in some men as they age. In the United States, osteoporosis is responsible for 300,000 hip fractures, 700,000 spine fractures and 250,000 wrist fractures each year. Associated health care costs are in the billions of dollars annually.

Adequate intake and metabolism of minerals can largely prevent osteoporosis. Dietary boron has been shown to affect several aspects of mineral metabolism in animal studies. And in a human study, 12 postmenopausal women were fed a diet deficient in boron (0.25 mg daily) for 119 days followed by a 48-day period in which they received supplements of 3 mg daily. On the boron-deficient diet, the women experienced increased loss of both calcium and magnesium. On the boron-supplemented diet, the opposite was true. Urinary excretion of calcium and magnesium was significantly diminished, and serum concentrations of 17 beta-estradiol, as well as testosterone, increased. The findings of the study suggest that maintaining adequate levels of boron, particularly in the presence of adequate levels of magnesium, can help prevent calcium loss and bone demineralization in postmenopausal women and, perhaps, others. The boron effect on testosterone levels, while possibly significant for women, would be too low to have any significance for men.

In a subsequent human study, boron supplementation increased serum levels of 25-hydroxycholecalciferol, a metabolite of vitamin D important in mineral metabolism, in postmenopausal women who were deficient in boron. There were also findings suggesting that estrogen replacement therapy used in conjunction with boron may have a synergistic effect. There is evidence to support the assertion that boron can both mimic and enhance some of the effects of estrogen in post-menopausal women.

Findings to date suggest that boron and calcium actions are inter-related or that the two elements affect similar systems, including the modification of hormone action, the alteration of cell membrane characteristics and/or trans-membrane signaling. Boron appears to be an important partner with calcium metabolism and as such might be expected to play an important role in the prevention of osteoporosis. Conclusive proof of this, however, remains to be demonstrated, though studies to date are suggestive of a positive effect.

Anecdotal reports, combined with some epidemiological findings, suggest that supplemental boron may alleviate the symptoms of osteoarthritis. There are reports that in those areas of the world where daily dietary intake of boron is 1 mg or less the estimated incidence of osteoarthritis ranges from 20 to 70%. In areas of the world where boron intakes are 3 to 10 mg daily, the estimated incidence of the disease ranges from 0 to 10%. This alone does not make a compelling argument for any role for boron in the prevention or treatment of osteoarthritis in the absence of clinical evidence. There is, however, one clinical study and one animal study that may justify further investigation.

The clinical trial involved 20 patients with radiographically confirmed osteoarthritis. This was a double-blind, placebo-controlled study in which half of the subjects were given 6 mg of boron daily while the other half received the placebo. The subjects were evaluated three times--prior to taking the tablets, after three weeks on the tablets and after eight weeks on the tablets. Patients were graded with respect to their symptoms as well as their use of a permitted analgesic. At the end of the eight-week period, 50% of those taking boron showed improvement, while only 10% of those on placebo showed similar improvement. The finding was declared statistically significant.

A recent study using rats indicated that dietary boron might be of benefit in adjuvant-induced arthritis. The benefits were evaluated by the amount of paw and joint swelling following adjuvant injection. A control group that did not receive boron was used for comparison. There was less swelling in the boron-supplemented animals. Measurements of natural killer cells, CD8 lymphocytes and neutrophils were also performed. The conclusion was that supplemental boron modulates the response to antigens of key immune cells and helps control the inflammatory process.

Further investigation is warranted and necessary before any conclusion can be made regarding the role of boron in the prevention and treatment of arthritis.

There is very preliminary evidence that supplemental boron may improve mental function. In one human study, subjects were first given a diet deficient in boron followed by a period in which they received supplemental boron in the amount of 3 mg daily. During the supplementation period, the subjects' electroencephalograms showed alterations suggesting improved behavioral activation (less drowsiness) and mental alertness. Improved psychomotor skills were also noted, along with improvement in attention and memory.

Studies have not supported the claim that boron can increase lean muscle mass. Studies show no effect on plasma testosterone levels or strength in male body builders. Claims to the contrary seem to have arisen from the studies on postmenopausal women, where boron may have induced a slight increase in plasma testosterone levels.

One observational study found an inverse relation between boron intake and prostate cancer. However, another observational study—the VITamins And Lifestyle (VITAL) cohort study—found no evidence among 35,244 males for a preventive role of boron intake on prostate cancer. Further research is needed to determine if boron has any role to play in the prevention of prostate cancer.

Contraindications, Precautions & Adverse Reactions

Contraindications

Known hypersensitivity to a boron-containing product.

Precautions

Because of the lack of long-term safety studies, supplemental boron should be avoided by pregnant women and nursing mothers except if recommended by their physicians.

Adverse Reactions

Doses up to 18 mg of boron daily appear to be safe for adults even if taken for prolonged periods of time. There is no evidence that boron is either carcinogenic or mutagenic. No adverse effects have been observed in either premenopausal or postmenopausal women using boron supplements.