Your Nutrients

Calcium D-glucarate is the calcium salt of D-glucaric acid, a natural substance found in many fruits and vegetables.

Calcium D-glucarate is available in capsules and tablets. Foods high in glucaric acid (a form of calcium D-glucarate) include apples, Brussels sprouts, broccoli, cabbage, and bean sprouts.

Calcium D-glucarate is not an essential nutrient, and thus no deficiency state exists.

Cancer

No side effects have been reported with calcium D-glucarate. Although there are no known drug interactions, many drugs (especially hormones) are metabolized in the liver by binding to glucuronic acid. It is therefore possible that taking calcium D-glucarate could increase the elimination of certain drugs or hormones from the body, thereby reducing their effectiveness. If you are taking any prescription medication, please consult your physician or pharmacist before taking calcium D-glucarate. At the time of writing, there were no well-known drug interactions with calcium D-glucarate.

Manufacturers of calcium D-glucarate recommend a daily intake of 200 to 400 mg.

Pyruvate (the buffered form of pyruvic acid) is a product created in the body during the metabolism of carbohydrates and protein.

Pyruvate is formed in the body as a byproduct of the normal metabolism of carbohydrates and protein and is present in several foods, including red apples, cheese, dark beer, and red wine. Dietary supplements of pyruvate are also available.

Because it is not an essential nutrient, pyruvate is not associated with a deficiency state.

Weight loss and obesity Athletic performance (for exercise performance) Athletic performance (for improving body composition with strength training in untrained people only)

High intakes of pyruvate can trigger gastrointestinal upset, such as gas, bloating, and diarrhea. One preliminary study in exercising women found 10 grams per day of pyruvate reduced blood levels of HDL (the “good” cholesterol) after one month. At the time of writing, there were no well-known drug interactions with pyruvate.

Most human research with pyruvate and weight loss has used at least 30 grams per day. However, such large amounts may not be necessary. In a six-week double-blind trial, as little as 6 grams per day of pyruvate in combination with exercise, led to greater weight loss and loss of body fat, compared with a placebo plus exercise.

Dehydroepiandrosterone (DHEA) is one of the hormones produced by the adrenal glands. After being secreted by the adrenal glands, it circulates in the bloodstream as DHEA-sulfate (DHEAS) and is converted as needed into other hormones.

DHEA is produced by the adrenal glands. A synthetic form of this hormone is also available as a supplement in tablet, capsule, liquid, and sublingual form. Some products claim to contain “natural” DHEA precursors from wild yam. However, the body cannot convert these substances into DHEA (although a series of reactions in a laboratory can make the conversion).

Meaningful levels of DHEA do not appear in food, and therefore dietary deficiency does not exist. Some people, however, may not synthesize enough DHEA. DHEA levels peak in early adulthood and then start a lifelong descent. By the age of 60, DHEA levels are only about 5–15% of what they were at their peak at younger ages. Whether the lower level associated with age represents a deficiency or a normal part of aging that should not be tampered with remains unknown. People with true adrenal insufficiency (i.e., Addison’s Disease; not the hypothetical adrenal “fatigue” or “burnout” that is sometimes incorrectly referred to as “insufficiency”) have below normal levels of DHEA. When women with adrenal insufficiency were treated with 50 mg of DHEA every morning for three or four months, their DHEA and DHEAS levels returned to normal, with a simultaneous improvement in well-being and sexuality. Some studies have reported lower DHEA levels in groups of depressed patients. However, in one trial, severely depressed people were reported to show increases in blood levels of DHEA. Despite these contradictory findings, a few clinical trials suggest that at least some people who are depressed may benefit from DHEA supplementation. (See “What does it do?” above for more information about use of DHEA supplements in the treatment of depression.) People with multi-infarct dementia (deterioration of mental functions resulting from multiple small strokes) may have lower than normal DHEAS levels, according to a preliminary trial. In this trial, intravenous injection of 200 mg per day of DHEAS for four weeks increased DHEAS levels and improved some aspects of mental function and performance of daily activities. People infected with HIV and those with insulin-dependent diabetes, congestive heart failure, multiple sclerosis, asthma, chronic fatigue syndrome, rheumatoid arthritis, osteoporosis, and a host of other conditions have been reported to have low levels of DHEA in most, but not all, studies. In most cases, the meaning of this apparent deficiency is not well understood. Men under 60 years of age with erectile dysfunction have been found to have lower DHEAS levels than men without the condition. (See “What does it do?” above for more information about use of DHEA supplements in the treatment of men with erectile dysfunction.) Most, but not all, studies have found that people with Alzheimer’s disease have lower blood DHEAS levels than do people without the condition.

Addison’s Disease (to correct deficiency) Crohn’s disease Depression Erectile dysfunction HIV support (for fatigue and depression) Lupus Schizophrenia Ulcerative colitis Alzheimer’s Disease Chronic fatigue syndrome Immune Function Menopause Multi-infarct dementia Osteoporosis Weight loss

Experts have concerns about the use of DHEA, particularly because long-term safety data do not exist. Side effects at high intakes (50–200 mg per day) appear to be acne (in over 50% of people), increased facial hair (18%), and increased perspiration (8%). In a preliminary trial, DHEA was also reported to induce less common side effects, including breast tenderness, weight gain, mood alteration, headache, oily skin, and menstrual irregularity in some people. Since this trial was not controlled, some of these less common “side effects” might have occurred even with a placebo. A case of mania has been reported in an older man who took 200–300 mg of DHEA per day for six months. However, in that case report, other causes of mania could not be ruled out. Significant increases in testosterone levels in both men and women have been reported in some trials. Other reports have found this change in women but not in men. An increase in testosterone might increase the risk of several cancers, and high amounts of DHEA have caused cancer in animals. Moreover, a possible link between higher DHEA levels and risks of prostate cancer in humans has been reported. At least one person with prostate cancer has been reported to have had a worsening of his cancer, despite feeling better, while taking very high amounts (up to 700 mg per day) of DHEA. While younger women with breast cancer may have low levels of DHEA, postmenopausal women with breast cancer appear to have high levels of DHEA, which has researchers concerned. Most, but not all, studies have found that as DHEA blood levels increase, so does the risk of breast cancer. Supplementation with high levels of DHEA (100 mg per day) has adversely affected other indicators of cancer risk in both women and men. Elevated DHEA levels have been reported to be associated with both higher, and lower risk for ovarian cancer. The reason for this discrepancy is unknown. The lack of knowledge about how DHEA supplementation might affect cancer risks provides a reason for caution. Until more is known, people with breast or prostate cancer or a family history of these conditions should avoid supplementing with DHEA. Although anticancer effects of DHEA have also been reported, they involve trials using animals that do not process DHEA the way humans do. Therefore, these positive effects may have no relevance for people. Some doctors recommend that people taking DHEA have liver enzymes measured routinely. Anecdotes of DHEA supplementation (of at least 25 mg per day) leading to heart arrhythmias have appeared. The relationship between DHEA, blood pressure, and heart disease is poorly understood. Increased blood levels of DHEAS have been associated with increased blood pressure and other cardiovascular risk factors in some, but not all, studies. One study found that people with hypertension had significantly decreased blood levels of DHEA. Until clinical trials clear up these inconsistencies and confirm its safety, people with hypertension should avoid using DHEA, except under the close supervision of a doctor. At only 25 mg per day, DHEA has lowered HDL cholesterol while increasing insulin-like growth factor (IGF). Decreasing HDL could increase the risk of heart disease. Increasing IGF might increase the risk of breast cancer. Certain medicines may interact with dehydroepiandrosterone. Refer to drug interactions for a list of those medicines.

Most people do not need to supplement DHEA. The question of who should take this hormone remains controversial. Some experts believe that daily intakes of 5–15 mg of DHEA for women and 10–30 mg for men are appropriate amounts for people with deficient blood levels of DHEA or DHEAS. While a few researchers suggest supplementation with as much as 50 mg per day in postmenopausal women, others consider this level excessive. People should consult a doctor to have DHEA levels monitored before and during supplementation. Healthy people with normal blood levels of DHEA or DHEAS should not take this hormone until more is known about its effects. However, some doctors recommend DHEA supplementation for selected people with depression, autoimmune diseases, or other problems, even if their blood levels are normal. People with systemic lupus erythematosus (SLE) have been shown to improve after taking 100–200 mg per day of DHEA. Such large amounts should never be taken without medical supervision. Discrepancies between label claims and actual DHEA content of DHEA supplements have been reported. Regrettably, the authors of this report failed to identify which brands were properly labeled and which were not.

IP-6 is a naturally occurring component of plant fiber.

IP-6, also known as phytate, is associated with dietary fiber and thus is naturally present in a wide variety of plant foods, especially wheat bran, whole grains, and legumes. Usual dietary intakes range from 1–1.5 grams phytate per day.

While there is no dietary requirement for IP-6, people consuming diets low in dietary fiber and nuts and seeds have the lowest intake.

Kidney stones

Phytate in foods has been associated with reduced mineral absorption. In particular, significant interference with iron absorption has been reported. People who are iron deficient should talk with a doctor before supplementing with IP-6. Even for those who are not iron deficient, if IP-6 supplements are taken for more than several months and fatigue a possible symptom of iron deficiency develops, a doctor should be consulted. How much iron supplementation (if any) should be used to counteract the iron-depleting effect of IP-6 varies from person to person, though many people are likely to not require such supplementation. At the time of writing, there were no well-known drug interactions with IP-6.

Virtually all research suggesting beneficial effects from taking IP-6 involve animals and not people. It is not known whether IP-6 would be useful for humans or if so, what would be the optimal amount.

Betaine (trimethylglycine) functions very closely with choline, folic acid, vitamin B12, and a form of the amino acid methionine known as S-adenosylmethionine (SAMe). All of these compounds function as “methyl donors.” They carry and donate methyl molecules to facilitate necessary chemical processes. The donation of methyl groups by betaine is very important to proper liver function, cellular replication, and detoxification reactions. Betaine also plays a role in the manufacture of carnitine and serves to protect the kidneys from damage. Betaine is closely related to choline. The difference is that choline (tetramethylglycine) has four methyl groups attached to it. When choline donates one of these groups to another molecule, it becomes betaine (trimethylglycine). If betaine donates one of its methyl groups, then it becomes dimethylglycine.

Dietary sources of betaine include fish, beets, and legumes. Betaine is most widely available as betaine hydrochloride (betaine-HCl), but that form is used primarily as a source of hydrochloric acid for people with hypochlorhydria (low stomach acid). The forms used specifically to provide betaine are betaine citrate and betaine aspartate. These forms have also been used to improve liver function.

Betaine is not an essential nutrient, and thus no deficiency state exists.

Alcohol-induced fatty liver Hepatitis (nonalcoholic steatohepatitis) Homocysteine (high) Atherosclerosis

No side effects with betaine at recommended levels have been noted. At the time of writing, there were no well-known drug interactions with betaine.

For people with alcohol-induced fatty liver, the recommended amount for betaine citrate or betaine aspartate supplementation is 1,000 to 2,000 mg three times daily. Lower amounts are often used as nutritional support for general liver health, although use of betaine in this manner has not undergone clinical research.

The amino acids ornithine and glutamine are combined to form ornithine alpha-ketoglutarate (OKG).

Although the amino acids that comprise OKG are present in protein foods such as meat and poultry and fish, the OKG compound is found only in supplements.

A deficiency of OKG has not been reported.

Wound healing

No side effects have been reported with the use of OKG. No clear interactions between OKG and other nutrients have been established. At the time of writing, there were no well-known drug interactions with Ornithine Alpha-Ketoglutarate.

Optimal levels remain unknown, though 10 grams per day has been used in clinical trials.

Methylsulfonylmethane (MSM) is a naturally occurring, organic, sulfur-containing compound related to another sulfur-containing substance, dimethyl sulfoxide (DMSO). MSM is found in small amounts throughout nature and has been detected in small amounts in the blood and urine of humans.

A precursor of MSM is formed initially by ocean plankton and released into the atmosphere, where it interacts with ozone and sunlight and returns to earth as MSM in rainfall. MSM can be taken up by plants and incorporated into their structure, but no measurement of the MSM content of foods has been done. Supplements containing MSM are available.

Although MSM is present in food, it is not an essential nutrient, so deficiency is not likely.

Osteoarthritis

According to some anecdotal reports, MSM has been used in human research for many years in amounts above 2000 mg per day with no significant adverse effects. However, diarrhea, skin rash, headache, and fatigue may be experienced in less than 20% of people, according to other anecdotal reports. Detectable levels of MSM in the brain of a person taking MSM supplements have been reported, but the significance of this finding, if any, is unclear. At the time of writing, there were no well-known drug interactions with methylsulfonylmethane.

Some authorities report anecdotally that 250–500 mg per day has beneficial effects on a variety of health problems. However, the only controlled trial using MSM used over 2000 mg per day to treat osteoarthritis. More research is needed before reliable recommendations for MSM supplementation can be made.

Lactase is the enzyme in the small intestine that digests lactose (the naturally occurring sugar in milk).

Lactase is produced by the body. Dairy products have varying levels of lactose, which affects how much lactase is required for proper digestion. Milk, ice cream, and yogurt contain significant amounts of lactose although for complex reasons yogurt often doesn’t trigger symptoms in lactose-intolerant people.

Only one-third of all people retain the ability to digest lactose into adulthood. Most individuals of Asian, African, and Native American descent are lactose intolerant. In addition, half of Hispanics and about 20 percent of Caucasians do not produce lactase as adults.

Diarrhea (for lactose-intolerant people) Indigestion and heartburn (for lactose-intolerant people) Irritable bowel syndrome (for lactose-intolerant people) Lactose intolerance

Lactase is safe and does not produce side effects. Some, but not all, studies suggest that lactose-intolerant individuals absorb less calcium. At the time of writing, there were no well-known drug interactions with lactase.

Lactose-reduced milk is available and can be used in the same quantities as regular milk. Lactase drops can be added to regular milk 24 hours before drinking to reduce lactose levels. Lactase drops, capsules, and tablets can also be taken directly, as needed, immediately before a meal that includes lactose-containing dairy products. The degree of lactose intolerance varies by individual, so a greater or lesser amount of lactase may be needed to eliminate symptoms of lactose intolerance.

L-tyrosine is a nonessential amino acid (protein building block) that the body synthesizes from phenylalanine, another amino acid. Tyrosine is important to the structure of almost all proteins in the body. It is also the precursor of several neurotransmitters, including L-dopa, dopamine, norepinephrine, and epinephrine.

Dairy products, meats, fish, wheat, oats, and most other protein-containing foods contain tyrosine.

Some people affected by PKU are deficient in tyrosine. Tyrosine levels are occasionally low in depressed people. Any person losing large amounts of protein, such as those with some kidney diseases, may be deficient in several amino acids, including tyrosine.

Stress Depression Phenylketonuria (for deficiency) Alcohol withdrawal support Parkinson’s disease

L-tyrosine has not been reported to cause any serious side effects. However, it is not known whether long-term use of L-tyrosine, particularly in large amounts (such as more than 1,000 mg per day) is safe. For that reason, long-term use of L-tyrosine should be monitored by a doctor. Vitamin B6, folic acid, and copper are necessary for conversion of L-tyrosine into neurotransmitters. Certain medicines may interact with L-tyrosine. Refer to drug interactions for a list of those medicines.

Most people should not supplement with L-tyrosine. Some human research with people suffering from a variety of conditions used 100 mg per 2.2 pounds of body weight, equivalent to about 7 grams per day for an average-sized person. The appropriate amount to use in people with PKU is not known, therefore, the monitoring of blood levels by a physician is recommended.

Fumaric acid is related to malic acid, and, like malic acid, it is involved in the production of energy (in the form of adenosine triphosphate [ATP]) from food.

Fumaric acid is formed in the skin during exposure to sunlight, as well as being available as an oral supplement and as a preparation for topical use.

No deficiencies of fumaric acid have been reported. However, some doctors suggest that people with psoriasis may have a biochemical defect that interferes with adequate fumaric acid production in the skin.

Psoriasis

Kidney disorders have been reported in people taking fumaric acid esters, possibly due to taking large amounts too quickly. Most studies have reported gastrointestinal upset and skin flushing as common side effects; some have also found decreased white blood cell counts with prolonged use. . At the time of writing, there were no well-known drug interactions with fumaric acid.

Only the esterified forms of fumaric acid are used therapeutically, such as fumaric acid monoethylester or fumaric acid di-methylester. Healthy people do not need to supplement with fumaric acid. Those using this substance (either orally or topically) should work with a dermatologist, since determining the optimal intake should be done on an individual basis. Even under these circumstances, supplementing should be started with small amounts (60–100 mg per day) and increased gradually over several weeks until an effect is noted.