Patricia L. Morse, Ph.D.

Estrogen blocks the absorption of magnesium, zinc, vitamin B6, and folate, and their deficiences sound a lot like the side effects a lot of us suffer from. This information is copied verbatim from the NHI OnDemand. It is long, but one reason I like this source is that it is so detailed about symptoms and sources.

Symptoms & Causes of Deficiency Although critical deficiency is rare in the U.S., marginal deficiency appears to be widespread with some studies reporting that approximately 75% of Americans ingest less than the RDA. Deficiency symptoms include muscle cramps, weakness, insomnia, loss of appetite, GI disorders, kidney stones, osteoporosis, nervousness, restlessness, irritability, fear, anxiety, confusion, depression, fatigue, and high blood pressure. Heart attacks: It is now known that many heart attacks occur in people with healthy hearts. Magnesium deficiency allows levels of calcium which can cause cardiac muscle spasm resulting in heart attack and frequently death.

• Food processing is a major cause of magnesium depletion. For example, up to 85% of magnesium is lost when whole wheat is refined to produce white flour.
• Modern farming techniques contribute to increasing soil depletion of magnesium. Artificial fertilizers used by farmers usually do not contain any magnesium.
• Poor food choices, excess calcium intake, intestinal malabsorption, alcohol abuse, liver and kidney disease, and diabetes can also cause deficiencies.
• Hypomagnesemia occurs in approximately 25% of patients with diabetes. Low levels of magnesium have been reported in childhood type 1 diabetes and in adults with type 1 or type 2 diabetes.

Overview Magnesium is a cofactor in over 300 enzymatic reactions in the body. It is necessary for the transmission of nerve impulses, muscular activity, temperature regulation, detoxification reactions, and for the formation of healthy bones and teeth. It also plays critical roles in energy production and the synthesis of DNA and RNA.

A U.S. Department of Agriculture survey revealed that approximately 75% of Americans do not ingest the RDA of magnesium, making it one of the most commonly deficient nutrients in our country. Suboptimal magnesium intake compromises all tissues, especially tissues of the heart, nerves and kidneys.

Magnesium is a nutritional superstar when it comes to cardiovascular disease. Magnesium deficiency is associated with increased incidence of atherosclerosis, hypertension, strokes, and heart attacks. Low levels of magnesium can cause stiffness in the vasculature, which elevates blood pressure and a contraction or spasm in the heart muscle, which can result in sudden death. It is now recognized that many heart attacks happen to individuals with relatively healthy hearts. It is a magnesium deficiency that causes a cardiac spasm which results in death.

Magnesium single-handedly influences many of the activities associated with a wide variety of cardiac medications. For example, magnesium inhibits platelet aggregation (like aspirin), thins the blood (like Coumadin®), blocks calcium uptake (like calcium channel blocking drugs such as Procardia®), and relaxes blood vessels (like ACE inhibitors such as Vasotec®). Magnesium also increases oxygenation of the heart muscle by improving cardiac contractibility.

Biological Function & Effect

• In general, magnesium is required for the metabolism of carbohydrates, proteins and fats, as well as activity related to calcium, phosphorus and vitamin C. It is vital for the health of nervous and muscular tissues throughout the body.
• Magnesium is a cofactor for oxidative phosphorylation in the production of ATP. As such, it is essential for the production and transfer of energy for protein and lipid synthesis, contractility of muscle, and nerve transmission.
• Heart disease: Adequate magnesium intake reduces the risk of cardiovascular disease and increases the rate of survival following a heart attack. If intravenous magnesium is given during the early stages of a heart attack, it results in a 70% decrease in deaths within one month following the event.
• Cardiovascular function: Magnesium influences many aspects of cardiovascular health. It acts to decrease platelet stickiness, helps thin blood, blocks calcium uptake, and relaxes blood vessels.
• Blood pressure: Over 30 reported clinical trials indicate that indicate magnesium can lower elevated blood pressure. However, the effect is usually only moderate, and thus magnesium should not be viewed as a primary treatment for hypertension.
• PMS: Numerous studies report that women with premenstrual syndrome have low levels of magnesium, and some studies report that magnesium helps to relieve PMS symptoms.
• Asthma: Various studies report low magnesium levels in asthma patients. Consuming adequate magnesium may reduce the risk of developing asthma and it is frequently useful as part of an overall treatment program.
• Bone: Magnesium may be more important than calcium for bone health. It is involved in calcium metabolism, the synthesis of vitamin D, and the integrity of skeletal bone-crystal formation.
• Teeth: Magnesium helps to bind calcium to tooth enamel, thus creating an effective barrier to tooth decay.

   

Side Effects & Toxicity Kidney excretion of excess magnesium makes magnesium toxicity rare. Excess magnesium intake frequently causes diarrhea.

RDA The RDA for magnesium is 400mg/day. Pharmacologic doses in the scientific literature range from 500-1500 mg/day.

Dosage Range 400-1000 mg/day

Dietary Sources The magnesium content in foods varies widely, as does the soil content of magnesium. Good food sources include nuts, legumes, cereal grains, and dark green leafy vegetables.

Forms Tablet; Capsule; Powder; Liquid; Spray

Symptoms & Causes of Deficiency Marginal zinc deficiencies are thought to be quite common in the United States, and because of its extensive range of biological activities, zinc deficiency can cause a wide range of deficiency symptoms. The symptoms of zinc deficiency include acne; impaired sense of smell and taste; delayed wound healing; anorexia; decreased immunity; frequent infections; depression; photophobia; night blindness; problems with skin, hair, and nails; menstrual problems; joint pain; and involuntary cyclical movements of the eyeball (nystagmus).

• Zinc deficiency conditions were first reported in the 1960s in growing children and adolescent males from Egypt, Iran and Turkey. Diets low in animal protein and high in phytate-containing grains produced symptoms of dwarfism, hypogonadism and failure to mature sexually.
• Pregnant women have greater zinc needs. Deficiency can cause impaired fetal development, low birth weight infants, and birth defects. Stretch marks during pregnancy are also partially due to zinc deficiency.
• Zinc deficiency can be caused by inadequate dietary intake due to foods grown on zinc-depleted soils. Food processing also removes zinc, so fast foods and processed foods are also zinc depleted.
• Protein and/or calorie-restricted diets can lead to zinc deficiency.
• Zinc depletion is frequently seen in the following medical conditions: alcoholism, macular degeneration, diabetes, malignant melanoma, liver and kidney diseases, malabsorption syndromes such as celiac sprue, and inflammatory bowel diseases such as Crohn's disease.

   

Overview Zinc is necessary for the functioning of well over 300 different enzymes and, as such, it plays a vital role in an enormous number of biological processes. Zinc is widely distributed in microorganisms, plants, and animals. In humans, the highest concentrations of zinc are found in the liver, pancreas, kidneys, bone, and voluntary muscles. Zinc is highly concentrated in parts of the eye, prostate gland, sperm, skin, hair, and nails.

Biological Function & Effect

• A few of zinc's important enzymatic activities include alcohol dehydrogenase, which works in the liver to detoxify alcohol; alkaline phosphatase, which frees inorganic phosphates to be used in bone metabolism; carbonic anhydrase which helps excrete carbon dioxide; zinc/copper-containing superoxide dismutase; cytochrome C, which is important in electron transport and energy production; carboxypeptidase which is necessary for the digestion of dietary proteins.
• Zinc is necessary in the synthesis of DNA and RNA, protein synthesis, cellular division, and gene expression. Zinc protects DNA from damage.
• Immunity: Zinc helps regulate a wide variety of immune system activities, including T lymphocytes, CD4s, natural killer cells, interleukin 2, and Zn/Cu superoxide dismutase.
• Zinc facilitates wound healing, especially in burns, surgical incisions, and other types of scars.
• Antiviral activity: Zinc enhances immune function in AIDS patients.
• Common cold: Zinc lozenges reduce the length and severity of colds.
• Infertility: Zinc is necessary for the maturation of sperm, for ovulation, and for fertilization.
• Zinc is necessary for normal growth and maturation.
• Skin conditions: Zinc is often useful in treating acne and eczema.
• Zinc is a critical regulator of the sensory perceptions of taste, smell, and vision. It controls salt-taste perception, and is necessary for dark adaptation and night vision.
• Zinc regulates vitamin A levels by controlling the release of stored vitamin A from the liver.
• Although zinc is a component of insulin, it does not appear to be a regulator of insulin activity.
• Zinc promotes the conversion of thyroxine to triiodothyronine.
• Zinc has anti-inflammatory properties and has been used successfully to treat some types of arthritis.
• Zinc is necessary for a healthy prostate gland and helps prevent benign prostatic hyperplasia (BPH).

   

Side Effects & Toxicity

• Zinc is relatively nontoxic, and although toxicity has been reported in humans, it is uncommon.
• Ingestion of high levels of zinc can induce a copper deficiency. Doses of 45 mg/day are safe, but regular intakes greater than 150 mg/day could be problematic.
• Zinc toxicity can cause diarrhea, dizziness, drowsiness, vomiting, muscle incoordination, and lethargy.
• Inhalation of zinc oxide in certain industrial environments can also be a source of excess exposure.
• Cooking acidic foods in galvanized cookware used to be a possible source of excess zinc intake. The widespread use of stainless steel and plastic materials to prepare and store foods has largely eliminated this problem.
• Galvanized pipes in older plumbing systems used to leach zinc into drinking water supplies, but modern plumbing has phased out the use of galvanized pipes.

   

Dosage Range 10-50 mg

Dietary Sources The best dietary sources of zinc are lean meats, liver, eggs, and seafood (especially oysters). Whole grain breads and cereals are also good sources of zinc.

Symptoms & Causes of Deficiency Deficiencies of vitamin B6 manifest primarily as dermatologic, circulatory and neurologic changes. Because of its many metabolic roles, there are a wide variety of deficiency symptoms, which include the following:

• Depression
• Sleep disturbances
• Nerve inflammation
• PMS
• Lethargy
• Decreased alertness
• Anemia
• Altered mobility
• Elevated homocysteine
• Nausea
• Vomiting
• Seborrheic dermatitis

Depression from inhibition of serotonin synthesis:
Vitamin B6 is an essential cofactor for 5-hydroxytryptophan decarboxylase, which is an enzyme that catalyzes one of the steps in the conversion of tryptophan to serotonin. Thus, a vitamin B6 deficiency can limit the brain's ability to synthesize serotonin. Low serotonin levels are associated with depression.

Sleep Disturbances from inhibition of melatonin synthesis:
To date, no studies have been conducted to evaluate insomnia and other sleep disturbances in people taking drugs that deplete vitamin B6. However, the metabolic pathways are well understood. Melatonin, which is our biochemical sleep trigger, is synthesized from serotonin in the brain. If a vitamin B6 deficiency inhibits serotonin synthesis, there will be a corresponding decrease in the body's ability to synthesize melatonin.

Elevated homocysteine:
Elevated homocysteine is now recognized as one of the most critical independent risk factors to cardiovascular disease. Homocysteine is a toxic intermediate metabolite in the metabolism of the amino acid methionine. It is capable of directly damaging the vascular system and initiating the process of atherosclerosis. Vitamin B6 is one of the nutrients that is required to metabolize homocysteine so that it does not build up in the blood and begin to damage the lining of the blood vessels.

PMS:
Vitamin B6 appears to influence estrogen-induced gene expression. A B6 deficiency results in a substantial increase in estrogen gene expression. Under these conditions excess estrogen may be produced, which may cause symptoms such as heavy menstrual flow, tender breasts, irregular bleeding, and emotional mood swings.

Vitamin B6 is one of the most commonly deficient nutrients in the United States. One U.S. Department of Agriculture study reported that approximately 80% of Americans consumed less than the RDA for vitamin B6.

Vitamin B6 is water-soluble; substantial amounts are lost in cooking and food processing.

In addition to the above-mentioned drugs that deplete vitamin B6, there are numerous substances in the environment which antagonize vitamin B6 such as alcohol, tobacco smoke, yellow dye #5 (tartrazine), PCBs, rancid fats in fried foods, the chemical used to accelerate the ripening process of fruits, to name a few.

Overview Vitamin B6 is necessary for the proper functioning of over sixty enzymes. Many of its activities are related to the metabolism of amino acids and other protein-related compounds such as hemoglobin, serotonin, various hormones, and the prostaglandins.

After entering a cell, vitamin B6 is phosphorylated, which converts it into its active form, pyridoxal phosphate (PLP).

Biological Function & Effect

• Many pyridoxal phosphate enzymes are involved with amino acid metabolism including: transamination (transfer of amino groups), deamination (removal of amino groups), desulfuration (transfer of sulfhydro groups), decarboxylation (removal of COOH groups).
• Necessary for the formation of hemoglobin and the growth of red blood cells.
• Essential for the synthesis of tryptophan, and the conversion of tryptophan to niacin.
• Required for the production of neurotransmitters derived from amino acids such as serotonin, GABA, norepinephrine, acetylcholine, and histamine.
• Facilitates conversion of glycogen to glucose for energy production.
• Useful in treating depression. Vitamin 136 is involved in the synthesis of serotonin.
• Useful in treating premenstrual syndrome associated with oral contraceptives (estrogens inhibit the absorption of vitamin B6).
• May be beneficial in the prevention and treatment of repetitive motion injuries such as carpal tunnel syndrome.
• Helps prevent atherosclerosis by metabolizing homocysteine.
• Some arthritics respond to pyridoxine. Since it is safe to use, it might be worth trying in all patients with arthritis.
• Many autistic infants respond to vitamin B6 (12 double-blind studies).

Symptoms of Toxicity Vitamin B6 can be neurotoxic when taken in large doses. Several cases have been reported in people taking 2 g or more per day. Symptoms included tingling in the hands and feet, decreased muscle coordination, and a stumbling gait. All recovered without problems.

RDA The RDA for vitamin B6 is 2 mg/day. Therapeutic dosage ranges in the scientific literature vary from 10 mg to 100 mg/day, although some applications go higher.

Dosage Range 2-100 mg/day

Dietary Sources

• The best sources of pyridoxine are brewer's yeast, wheat germ, organ meats (especially liver), peanuts, legumes, potatoes, and bananas.
• Vitamin B6 is also synthesized by the "friendly" intestinal bacteria.

Forms Tablet; Capsule; Liquid; Spray, liposomal; Tablet, effervescent; Powder

Symptoms & Causes of Deficiency Folic acid deficiency harms DNA metabolism, which causes abnormal cellular development, especially in cells with the most rapid rates of turnover, red blood cells, leukocytes, and epithelial cells of the stomach, intestine, vagina and uterine cervix. Folic acid needs are greater during pregnancy. Folic acid is one of the most common vitamin deficiencies. It is easily destroyed by heat, light and oxygen. Substantial losses occur in cooking and storage.

Symptoms of folic acid deficiency include megaloblastic anemia, birth defects, cervical dysplasia, elevated homocysteine, headache, fatigue, hair loss, anorexia, insomnia, diarrhea, nausea, increased infections.

Anemia: Folic acid is necessary for the production of red blood cells (erythrocytes) which carry oxygen from the lungs to the tissues and carbon dioxide from tissues to the lungs. Folic acid deficiency results in anemia and reduced tissue oxygenation. This results in a condition known as megaloblastic anemia, which is a condition characterized by enlarged nucleated abnormal red blood cells. This condition can produce symptoms of tiredness, weakness, diarrhea, and weight loss.

Birth defects: Folic acid helps regulate neural development and the transfer of genetic material to new cells. Numerous drugs have been shown to deplete folic acid. During pregnancy, the rapidly growing fetus substantially increases a woman's need for folic acid and folic acid deficiency during pregnancy dramatically increases the risk of birth defects such as spina bifida and cleft palate. The link between folic acid deficiency and birth defects is so strong, I recommend that all women have their folic acid status checked before trying to become pregnant. If this practice were followed, thousands of birth defects would probably be prevented each year. A laboratory test called the Neutrophilic Hypersegmentation Index (NHI) has been developed that can identify the earliest stages of folate insufficiency.

Cervical dysplasia is a term that refers to the development of abnormal cells in the uterus. It is a precancerous condition that is usually discovered when a woman has her annual PAP exam. This condition may contribute to an increased number of hysterectomies. Over 800,000 women have hysterectomies every year in the United States. Some professionals believe that the folic acid depletion caused by oral contraceptives is linked to this high incidence of cervical dysplasia and hysterectomies.

Elevated homocysteine, also known as hyperhomocysteinemia, is now recognized as a serious independent risk factor to cardiovascular disease. Excess homocysteine is capable of causing direct damage to vascular endothelial cells, and thus it is now being called an arteriosclerotic agent. It has been reported that even moderate elevations of homocysteine represent increased risk for the development of arteriosclerosis and thrombosis. Overview Folic acid is a member of the B vitamin group. Isolated in 1946 from spinach leaves, its name comes from folium, the Latin word for leaf. In the body, folic acid is converted to its biologically active form tetrahydrofolic acid (THFA). Niacin and vitamin C are necessary for this conversion. Structurally, folic acid consists of a pteridine (containing two rings) nucleus, conjugated with para-aminobenzoic acid, and glutamic acid. Hence, its chemical name is pteroylmonoglutamate.

Biological Function & Effect Like vitamin B12, folic acid is intimately involved in the synthesis of both DNA and RNA. Hence, it is essential for proper cellular division and the transmission of our genetic code to all newly formed cells.

• Folic acid may protect against certain types of cancers including precancerous cervical dysplasia in women (especially those taking oral contraceptives), bronchial squamous metaplasia in long-time heavy cigarette smokers, and dysplasia associated with ulcerative colitis and colon cancer.
• Folic acid prevents birth abnormalities such as neural tube defects, cleft palate and cleft lip.
• Essential for the healthy maturation of both red and white blood cells.
• Folic acid supplementation has been shown to prevent and reverse cervical dysplasia, which is recognized as a precancerous condition.
• Folic acid is required for the conversion of homocysteine to methionine. High blood levels of homocysteine are associated with the development of atherosclerosis.

Symptoms of Toxicity Folic acid is essentially nontoxic, even at very high doses. Large doses of folic acid can mask an underlying vitamin B12 deficiency, which if gone undetected, could result in irreversible nerve damage. Consequently, folic acid is limited to 400 mcg in OTC nutritional supplements.

RDA The RDA for folic acid is 200 mcg/day. Pregnant and lactating women require dosages higher than the RDA. Pharmacologic dosages in the scientific literature range from 400 mcg up to 4,000 mcg.

Dosage Range 200-800 mcg/day; however, physicians occasionally need to administer doses to severely deficient patients ranging from 5000-10,000 mcg/day. Supplementation in patients receiving phenytoin and/or co-trimoxazole should not be initiated without consultation with the prescriber. For additional information, see "Scientific Basis" field in phenytoin and co-trimoxazole monographs.

Dietary Sources

• Folic acid occurs in a wide variety of foods. Best sources include dark green leafy vegetables, brewer's yeast, liver, and eggs.
• Other good sources are beets, broccoli, Brussel sprouts, orange juice, cabbage, cauliflower, cantaloupe, kidney and lima beans, wheat germ, whole grain cereals and breads.
• Folic acid is also synthesized by the "friendly" intestinal bacteria.

Forms Tablet; Capsule; Liquid; Spray, liposomal; Tablet, effervescent