Selenium (Se)

Selenium (Se)

Mineral Health Connection

Over 200 years ago, Jöns Jacob Berzelius discovered the element selenium, which he named after the goddess of the moon, Selene. Aside from its industrial applications, selenium is an essential trace nutrient that is found in seafood, liver, lean red meat, and grains that are grown in selenium-rich soil. A deficiency in selenium is a severe obstacle in areas of the world where the soil contains little selenium such as the case in the United Kingdom, Australia, New Zealand (source) and some areas of China (source) among others.

Supplementing doses above the RDA (40 to 70 μg) is required to inhibit genetic damage and cancer (>100 μg). The most recent revision of of the RDA for selenium is based on the estimated average requirement (EAR) required to maximize the antioxidant enzyme glutathione peroxidase (GPx) activity in plasma (source) and not necessarily for seleniums anticarcinogenic effects. Excessive doses of selenium may cause oxidative damage leading to genomic instability which raises the question, how much is enough? In this article, I try and find clarity regarding this question and bring transparency to selenium and its supplementation.

Americans have been advised that supplementation is not needed on the basis of the EAR and their serum concentrations being met according to the National Health and Nutrition Examination Survey (NHANES III) (source). However, selenium intake is on the decline in many areas of the world due to the effect of sulphur-based fertilisers on crops such as wheat (source).

Worldwide, up to one in seven people have been estimated to have low dietary selenium intake. Using moderate climate change projections, it has been predicted that future soil selenium losses from 58% (between the year 2080–2099). Predicted losses from croplands were even higher, with 66% of croplands predicted to lose 8.7% selenium. These losses could increase the worldwide prevalence of selenium deficiency (source).

Selenium has a protective effect against some forms of cancer and may enhance male fertility, decrease cardiovascular disease mortality, and regulate inflammatory mediators in asthma (source). It has also been proposed that optimal selenium levels may potentially be useful for decreasing the risk of atherosclerosis, cataracts, emphysema, inflammatory-immune disease, senile dementia, aging, and rheumatoid arthritis.

Selenium prevents cellular and subcellular lipids and fats from being peroxidized, which means it prevents body fats from going rancid (seen externally as “age spots” or “liver spots” called ceroid lipofuscin). Iron chelators such as desferrioxamine and antioxidants such as vitamin E, glutathione, and selenium may slow lipofuscin accumulation (source). An exclusive and indispensable role of selenium noted in that it is required to prevent hydroperoxide-induced ferroptosis, preventing fatal epileptic seizures and protecting the brain (source). A subclinical selenium deficiency seems to be associated with reduced immunocompetence, depression, thyroid imbalances and reproduction difficulties in both sexes.

Mechanism of action:

Selenium is essential for the amino acid Selenocysteine, the 21st essential amino acid (source). Selenium exerts various biological functions which are found in at least 25 selenoproteins. Selenoproteins are involved in diverse roles such as stabilizing the integrity of the sperm flagella and are essential for thyroid hormone metabolism aiding conversion of thyroxine (T4) to the active thyroid hormone, 3,3′5-triiodothyronine (T3). Selenium is a vital component of several significant metabolic pathways such as protection from neurodegeneration, maintaining lens cell viability, and reducing oxidative damage during aging. (source, source).

Selenium is a significant contribution to the anti-oxidant system. As a component of glutathione peroxidase, selenium acts as an antioxidant and has a sparing effect on vitamin E. Glutathione peroxidase blocks the generation of free radicals that destroy polyunsaturated fatty acids in cell membranes. Cellular and plasma glutathione peroxidase is the functional parameter used for the assessment of selenium status in the body, though hair and nails are also valuable and accurate. Selenium enhances the enzyme required for the detoxification of xenobiotic chemicals in the liver, glucuronyl transferase, and is involved in the regulation of prostaglandin synthesis and the degradation of intracellular peroxides.

Selenium is believed to encourage the immune system (source) and has been postulated to reduce the risk of cancer by a variety of mechanisms (source, source). Though the potential benefits of selenium supplementation in tumour patients are undeniable (source). By enhancing the stability of the genome inhibiting carcinogen-induced covalent DNA adduct formation, selenium may also reduce the risk of cancer, retard oxidative damage to DNA, lipids, and proteins, retarding angiogenesis, and modulating cellular events critical in cell growth inhibition. Laboratory studies, that have demonstrated oxidative stress induced by sodium selenite at high concentrations in both acute and chronic treatments of prostate cancer cells, have proposed different mechanisms were involved (source). After acute exposure to selenite, cells presented mitochondrial injury and cell death, mainly by apoptosis. While chronic exposure of selenium exerted its effects on human prostate cancer cells by altering the intracellular redox state, subsequently blocking the cell cycle.

Food sources:

The selenium content of foods is largely dependant on soil levels. It can generally be found in brewers yeast, kelp, seaweed, brazil nuts, seafood (e.g. tuna, herring), garlic, milk, eggs, and kidneys.

Dose:

The RDA for selenium is 55 μg for healthy adult males and 55 to 75 μg for healthy females. The RDA for children starts at 15 μg and increases to 40 μg by the age of 9 years. The therapeutic dose range is 200 to 800 μg/day and does not lead to toxicity (source). Selenium has a narrow safety margin, with clinical toxicity reported on daily doses of 1000 to 2000 μg over a month. The dose for long-term use is believed to range between 100 to 400 μg. Extrapolation from animal experiments suggests that 400 to 700 μg/day may be needed for cancer protection. Since 400 μg daily is probably the upper limit of safety, daily doses of 100 to 200 μg may be more realistic and safe objectives for inhibiting genetic damage and carcinogenesis in humans(source, source). Such recommendations are contrary to the traditional nutritional essentiality paradigm; however, as such advice is consistent with a better health outcome, perhaps it is time that the paradigm is reviewed (source, source).   

One of the safest selenium supplements is selenium organically bound to yeast. Yeast-based selenium is approximately 40% selenomethionine, 20% other amino acid conjugates (e.g., selenocysteine, methylselenocysteine), and 40% unidentified selenopeptides (source). Doses of 500 to 1000 μg have been observed to be well tolerated. Another safe form of organic selenium is selenomethionine at doses of 200mcg (source). Selenomethionine appears more effective at increasing selenium status; while selenite and selenate are more bioavailable than selenomethionine. In one animal study, co-administration of vitamin C suppressed the chemopreventive effect of inorganic selenium (selenite), but not those of selenomethionine.

Animal studies have established that the dose and form of selenium compounds are critical factors in regard to circumscribing cellular responses, inorganic selenium at doses up to 10 μmol, and organic selenium compounds at doses equal to or greater than 10 μmol achieve distinctly different cellular responses (source). Animal studies using multiple different tumorigenesis models have mainly found that selenium has notable chemopreventive activity.

Clinical Uses:

Biochemical changes produced by selenium deficiency predisposes people who experience additional stresses to develop certain illnesses (source). Insufficient selenium intake has been estimated to affect up to 1 billion people worldwide (source). Selenium has cancer-protective effects (source, source, source, source). In a placebo-controlled human trial, supplementation of 200 μg selenium from 0.5 g brewer’s yeast has been determined to decrease the incidence of several types of cancers (source). This prospective study found that a daily supplement of 200 μg selenium over an average of 4.5 years revealed no protective effects against the primary endpoint of squamous and basal cell carcinomas of the skin. However, the selenium-treated group did have substantial reductions in the incidence of prostate cancer and total cancer incidence and mortality(source). This dose is three or four times the RDA. Nevertheless, such findings are supported by epidemiologic studies, which have shown that low selenium status is associated with an increased total cancer incidence, particularly of gastrointestinal, prostate, and lung cancers (source). Surely, epidemiologic, laboratory and serendipitous results of two randomized clinical trials suggest that men with high selenium and vitamin E intake have a lower risk of prostate cancer (source). In addition, a case-control study has also found that low plasma selenium is associated with a four-to-five-fold increased risk of prostate cancer (source).
It should be noted that the reduced levels of prostate-specific antigen (PSA), a commonly used marker for prostate cancer, observed with selenium supplementation are expected due to the effect of selenium on cancer cells and not because of selenium interfering with the production of PSA for any reason other than a decrease in cancer cells. A useful indicator in the disease progression in individuals is the change in serum PSA levels during selenium supplementation (source).

Due to the fact that plasma selenium decreases with age, supplementation may be beneficial to older men. It appears that low selenium serum levels have a correlation with cancer of the head, neck (source) and lung (source). Low selenium serum levels have also been associated with increased risk of thyroid cancer and may play a role in carcinogenesis (source). In addition, serum concentrations of selenium are significantly decreased in patients with malignant tumours (source).

While the protective effect of selenium against cancer and the low serum level of selenium is fairly well documented, there is less clinical evidence to support the anti-inflammatory effect of selenium in arthritis. A clinical trial failed to demonstrate that selenium treatment (200 μg/day) produced any clinical benefit in the case of rheumatoid arthritis. However, when examining the quality of life, there was a significant improvement in arm movements and health feeling in selenium-treated patients (source).

The Human Immunosuppression Virus (HIV) depletes the body stores of selenium, which, in turn, cause the immune system failures manifested as Acquired Immunodeficiency Disease Syndrome (AIDS). Selenium supplementation has been shown to forestall the progression of HIV infection to developing AIDS, to reduce the symptoms of AIDS and to improve the lifespan of AIDS patients. (source, source, source)

Selenium can up-regulate genes related to phase II detoxification enzymes, certain selenium-binding proteins and select apoptotic genes, while down-regulating those related to phase I activating enzymes and cell proliferation. Independent of tissue type, selenium arrests cells in G1 phase of cell cycle, inhibits CYCLIN A, CYCLIN D1, CDC25A, CDK4, PCNA and E2F gene expressions while influencing the expressions of P19, P21, P53, GST, SOD, NQO1, GADD153 and certain CASPASES. In addition to those described above, genes such as OPN (involved in metastasis) has been reported to be down-regulated by selenium (source)

Animal studies suggest other areas for investigation. It is possible that selenium deficiency and vitamin E deficiency can activate latent viruses such as herpes (source). Animal studies have also shown that mice on either selenium or vitamin E deficient diets developed myocarditis when exposed to coxsackievirus infection; those with adequate selenium or vitamin E status did not (source). Viral-induced neuropathy was found to abate once selenium, vitamin E, carotenoid, and riboflavin blood levels were increased. It appears that a normally avirulent viral genome may become pathogenic in a nutritionally deprived host. An experimental animal study has also found that growth retardation induced by selenium deficiency is associated with impaired bone metabolism and a reduction in bone mineral density (source).

It appears that selenium is critical for healthy sperm and may improve fertility and the chance of a successful conception for both men and women. Supplementation in the case of selenium deficiencies in the procreation period of both women and men is of utmost significance to prevent gestational complications, miscarriages and the damaging of the nervous and immune systems of the fetus as well as to promote fertility (source). 56% of subfertile men with low selenium status showed a positive response to selenium supplementation, improving sperm motility and the chance of successful conception. This study highlights the inadequate provision of this essential element in the Scottish diet (source).

Hair Test Notes:

There are moderate correlations between selenium levels in whole blood, serum, toenails and hair and correlate with dietary intake assessed through dietary records and food frequency questionnaires (source, source, source, source). Thus hair mineral analysis (HMA) may be a useful tool in monitoring selenium treatment (source) or occupational exposure (source). There is a good correlation between hair and plasma selenium levels in healthy children (source)

Selenium can protect and antagonise arsenic and has the potential to mitigate arsenic toxicity (source). As well as a mutual antagonism between mercury (source), cadmium (source), silver (source), thallium and selenium (source, source). Excess storage of iron can be produced by deficiencies of selenium, copper, zinc, and is wrongly blamed for liver cirrhosis, fibrosis of the pancreas, hypertrophic cardiomyopathy and diabetes. These diseases are not the direct result of iron excess, but rather a deficit or biounavailability of the elements listed above.

High Hair Selenium

High hair selenium can be due to the use of shampoos containing selenium may indicate a loss of selenium through the hair.

Low Hair Selenium

Low hair selenium may be due to dietary deficiency, which is relatively common, especially among those who eat refined foods.

Toxicity or Drug interactions:

Selenium toxicity is increased in animals with low or depleted stores of vitamin E. Chronic ingestion of more than 0.6 mg/day can cause toxicity.

Possible Symptoms of Selenium Toxicity

  • Garlic breath

  • Paresthesia

  • Rough Hair

  • Hair loss

  • Nausea

  • Gastric disturbances

  • Brittle fingernails

  • Dermatitis

  • Hepatorenal damage

  • A metallic taste

  • Nervous irritability

  • Depression

  • Unusual fatigue

  • Vomiting

  • Lameness

  • Pain

  • Sloughing of skin

  • Erosion of joints

  • Liver cirrhosis

  • Cardiac Atrophy

  • Lowered conception rates

  • Anemia

  • Birth defects

  • Muscle spasms

Clinical Caution:

  • Less than 11mcg selenium daily is considered to unquestionably put people at risk of selenium deficiency and genetic damage (source). An increased risk of cancer is suspected to be associated with selenium deficiency. Clinically, conclusions consistent with selenium deficiency include fingernail and skin changes, cardiomyopathy (source), and skeletal muscle fatigue, tenderness, and weakness.

  • Patients on monoamine inhibitors should avoid yeast-containing selenium products.

  • Although an adequate vitamin C status is necessary for normal selenium metabolism, megadoses of vitamin C may decrease absorption of selenium taken as sodium selenite (source).

  • Selenium deficiency could exacerbate iodine deficiency (source).

  • Smoking tends to lower selenium biomarker concentrations, even though smoking is a source of selenium exposure - a phenomenon that might be related to increased excretion of the metalloid due to interaction with cadmium or other heavy metals (source, source)

Selenium Deficiency Diseases:

  • HIV (AIDS) Anemia (RBC fragility)

  • Age Spots & Liver Spots–ceroid lipofucin

  • Fatigue Muscular weakness

  • Myalgia (Fibromyalgia, muscle pain and soreness)

  • Rhabdomyalisis (breakdown of skeletal muscle cell walls following exercise)

  • Scoliosis

  • Muscular Dystrophy (MD, White Muscle Disease, Stiff Lamb Disease)

  • Cystic Fibrosis Cardiomyopathy (Keshan Disease, “Mulberry heart” disease)

  • Multiple sclerosis (MS) Blindness – cataracts, macular degeneration Heart palpitations Irregular heart beat

  • Liver cirrhosis

  • Pancreatitis

  • Pancreatic atrophy

  • Lou Gehrig’s disease (ALS)

  • Parkinson’s Disease

  • Alzheimer’s Disease

  • Adrenoleukodystrophy (ALD – “Lorenzo’s Oil” Syndrome)

  • Infertility

  • Low birth weight

  • High infant mortality

  • Miscarriages

  • Sudden Infant Death Syndrome (SIDS)

  • Cancer

  • Clinical AIDS (HIV infection)

  • Pathogenic viruses

  • Sickle-cell anemia; thalassemia

  • Wilson’s Syndrome (hypothyroidism)

  • Hyperthyroidism

Practice Tips:

  • Animal studies have shown selenium causes birth defects when given in large doses.

  • Close monitoring of patients on selenium supplementation is necessary.

  • Vitamin E 500 IU enhances the efficacy of selenium.

  • Selenium and vitamin E have closely related mechanisms of action, and deficiency in one often overlaps with a deficiency in the other.

  • Muscular pain associated with selenium deficiency may be corrected with 200 μg daily.

  • Selenium modulates T lymphocyte-mediated immune responses and stimulates peripheral lymphocytes to respond to antigens.

  • Selenium 200 μg daily combined with beta-carotene 15 mg and vitamin E 500 IU may reduce the risk of cancer.

  • Selenium does not protect against skin cancer, whether it be basal or squamous cell cancer.

  • Those with low levels of selenium before selenium supplementation had a significantly lower incidence of lung cancer due to selenium supplementation (source, source)

References:

https://lpi.oregonstate.edu/mic/minerals/selenium

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5432259/

https://www.ncbi.nlm.nih.gov/pubmed/18444146

https://ker.com/equinews/selenium-deficiency-or-toxicity-horses/

http://seleniumfacts.com/dr-schrauzer-selenium-researcher/

https://www.sciencedirect.com/science/article/pii/S0006306100801647?via%3Dihub

https://www.ncbi.nlm.nih.gov/pubmed/19514891

https://www.ncbi.nlm.nih.gov/pubmed/14713754

https://ods.od.nih.gov/factsheets/Selenium-HealthProfessional/#en6

https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD005195.pub4/epdf/standard

http://www.selcote.com.au/selenium-deficient-areas/

https://www.lifeextension.com/magazine/2012/ss/selenium-protect-against-cancer/page-01

http://seleniumresearch.com/

https://www.ncbi.nlm.nih.gov/pubmed/1702669

https://www.ncbi.nlm.nih.gov/pubmed/3552651

https://link.springer.com/article/10.1007/BF01989914

https://www.ncbi.nlm.nih.gov/pubmed/10894365













Vitamin E

VitaminE.jpg

Introduction

Vitamin E was the fifth vitamin discovered and hence its name. The existence of vitamin E was first recognized in 1922. It was observed that female rats required a previously unknown dietary factor to maintain pregnancies. Deficient females would ovulate and conceive properly; however, at some point in the pregnancy a spontaneous miscarriage would occur; additionally, lesions in the male’s testes were reported.

It has been estimated that by simply taking just 100 IU of vitamin E daily for those over 50 could save 5-6 billion dollars (source). Vitamin E is a fat-soluble nutrient that has eight active and naturally occurring plant constituents called tocopherols and tocotrienols. The various forms of vitamin E have overlapping and subtle biologic activities. Tocotrienols are less critical for biological physiology than tocopherols. Though tocotrienols have higher antioxidant activity than tocopherols, they have lower bioavailability following oral consumption.

In comparison to alpha- (α-), beta- (β-), gamma- (γ-), and delta- (δ-) tocopherols are less biologically active. Various studies indicate that the body, through specific mechanisms prefers the accumulation of α-tocopherol after absorption. Vitamin E is found in various foods such as seeds and grains. However, the consumption of polyunsaturated fatty acids (PUFA's) increase the need for vitamin E (source, source, source). Vitamin E enhances vitamin A utilisation and functions as an antioxidant and antiestrogenic compound. At high doses, it inhibits platelet aggregation. Vitamin E and other nutrients may have protective effects against cancer, cardiovascular disease, diabetes and cataracts. Serum γ- and α-tocopherol concentrations are highly correlated with serum cholesterol and triglycerides (source, source).

Mechanism of Action

Vitamin E has a critical antiestrogenic (source, source), antioxidant (source)and cell signalling (source) activities. Tocopherols and tocotrienols are part of an interlinking set of antioxidant cycles which form an antioxidant network (source, source). Vitamin E acts directly on many oxygen radicals such as singlet oxygen, lipid peroxide products and superoxide radicals to form the relatively harmless tocopherol radical, protecting from lipid peroxidation (source). α-tocopherol can perform either as an antioxidant or as a prooxidant to promote the lipid peroxidation of LDL. Some have suggested that vitamin E may only be effective alongside vitamin C because it has been shown that the prooxidant activity of α-tocopherol is inhibited by ascorbate which acts as a co-antioxidant (source). Vitamin E also functions in conjunction with the trace element selenium, a cofactor for glutathione peroxidase, and other enzymes such as superoxide dismutase and catalase.

Through its ability to modulate platelet aggregation, α-tocopherol has been shown to play a crucial role in influencing the atherosclerotic process, endothelial dysfunction and inhibiting the activity of protein kinase C, an essential player in several signal transduction pathways (source). The antioxidant effect of vitamin E on LDL potentially retards atherosclerosis. In addition to its protection of nitric oxide, its inhibition of smooth muscle cell proliferation, its inhibition of adhesion to vascular endothelium of monocytes, platelets including other cells, and its modifications of eicosanoid production by neutrophils and monocytes (source). Due to its anti-inflammatory effect, vitamin E may protect against the progression of atherosclerosis. Vitamin E decreases the release of reactive oxygen species (ROS) and reduces lipid peroxidation, moreover, it reduces cytokines such as interleukin-1ss (IL-1ss) and tumour necrosis factor-alpha (TNF-α) along with decrease the adhesion of monocytes to human endothelium in doses of 1,200 IU daily (source). By inhibiting the activation of protein kinase C activity and nuclear factor-kappa B (NF-kappa B) vitamin E prevents leukocyte-endothelial cell adhesion by inhibiting signal transduction involved in the surface expression of adhesion molecules of leukocytes and endothelial cells (source), protecting from inflammation and atherosclerosis. Vitamin E supplementation has also been shown to improve endothelial-dependant vasodilation (source).

The form of vitamin E dictates its biological functions. α-tocopherol is the more effective chain breaking antioxidant for halting lipid peroxidation, while γ-tocopherol is much more effective at to trap lipophilic electrophiles like reactive nitrogen oxide species (source). Both α-tocopherol and γ-tocopherol can prevent smooth muscle cell proliferation by inhibiting the activity of protein kinase C. However, only γ-tocopherol and its metabolites which are water-soluble inhibit cyclooxygenase-2 (COX-2) activity in intact cells and capable of blocking the synthesis of prostaglandin E2 in lipopolysaccharide-stimulated macrophages and interleukin 1β activated epithelial cells. γ-tocopherol has properties that are not shared with α-tocopherol. γ-tocopherol is more effective as an anti-inflammatory and more efficient at quenching reactive nitrogen oxide species that are generated in chronic inflammation.

Tocotrienols benefit cardiovascular disease by inhibiting LDL oxidation and down-regulating 3-hydroxyl-3-methylglutaryl-coenzyme A (HMG CoA) reductase, which is an essential enzyme of the mevalonate pathway (source). In addition, tocotrienols are capable of penetrating quickly through the skin and efficiently combatting UV or ozone-induced oxidative stress. Moreover, critical and novel anti-proliferative and neuroprotective effects of tocotrienols may be independent of their antioxidant activity (source).

Food Sources

Vitamin E can be found in wheat-germ oil, and vegetable oil, along with their seeds such as sunflower, avocado, sweet potato etc., and nuts such as hazelnuts, almonds, pecans, and peanuts. Substantial amounts of vitamin E may be lost due to processing, storage or cooking. A controlled study on healthy individuals confirmed that the plasma concentration of vitamin E and plasma antioxidant activity in response to oral supplementation of vitamin E are notably affected by food intake (source). It should be noted that vitamin E appears to be a poor indicator of plasma levels of vitamin E (source).

Furthermore, while increasing dietary vitamin E intake can increase plasma α-tocopherol levels, the amount of dietary modifications required to achieve potential cardioprotective levels of plasma α-tocopherol is unlikely in practice (source), and supplementation may be required. Due to the lipophilic nature of vitamin E, its absorption is increased with food intake and should be taken with meals. The requirement for vitamin E is closely related to the dietary intake of polyunsaturated fatty acids (PUFA). Vitamin E is metabolically consumed by a protective mechanism to prevent PUFA from being peroxidised. Thus some foods generally considered as sources of vitamin-E, as concluded from their gross vitamin E content, can cause a vitamin E deficiency if not sufficiently compensated by other vitamin E supplying food constituents (source). γ-tocopherol is the most prevalent form of vitamin E and is found in plant seeds, yet α-tocopherol is the form of vitamin E typically found in supplements. Interestingly, while the body preferentially accumulates α-tocopherol, γ-tocopherol has properties which are not shared by α-tocopherol.

Dose

The RDA for vitamin E is currently set in mg, though many supplement companies prefer to use International Units (IU’s). Depending on the source, the current RDI for vitamin E varies from 12-30 IU each day. In the year 2000, the Food and Nutrition Board of the Institute of Medicine published a new dietary reference intake of 15mg (22.4IU) (source). The increase in the RDA has been challenged and supported by others (source, source). The tolerable upper intake level has been reported to be 1,000mg (1,100IU) daily. Careful dietary selection may allow one to transcend the RDA of vitamin E. But it does not take into consideration the vitamin E depleting capacity of PUFA's (source), failing to reach the 100 IU per day minimal therapeutic recommendation (source), the 200IU which appears to be optimal for the immune status of the elderly, or the 400-800 IU that is necessary to reduce the risk of cardiovascular disease (source).

In addition to consuming 5-8 servings of fruit and vegetables in their daily diet, it has been suggested that people should take a supplement of 200 IU vitamin E (source). Vitamin E supplementation is not free of downsides. Synthetic vitamin E is a mixture of 8 isomers, of which only one has the RRR configuration that is found in natural vitamin E. The relative potency remains unproven, though in animals the potency of natural vs synthetic vitamin E is 1.36 (source). In comparison to the natural stereoisomer, RRR-alpha-tocopherol acetate, synthetic vitamin E is an equimolar mixture of eight stereoisomers (source).

The different tocol and tocotrienol derivatives alpha- (α-), beta- (β-), gamma- (γ-), and delta- (δ-) have differing roles and diverse tissue affinities (source). An example is that studies are suggesting γ-tocopherol is required to adequately remove peroxynitrite-derived nitrating species despite α-tocopherols action as an antioxidant (source). Large doses of dietary α-tocopherol have been shown to displace γ-tocopherol in other tissues and plasma and may block this action, which may mean that the current wisdom of vitamin E supplementation with primarily α-tocopherol may require review and it may be beneficial to supplement with a full spectrum vitamin E supplement to gain the most benefit. Variations in the biologic activity of different forms of vitamin E presumably reflect the ease with which each molecule attaches to the cell surface. The biological activity of d-α-tocopherol is 1.49 IU/mg; in contrast, d-γ-tocopherol has a lower biologic activity of 0.15 IU/mg. Certainly, the vitamin E structure dictates its potency.

The standard for calculating the vitamin E content of food is α-Tocopherol content. One mg of natural vitamin E (RRR-α-tocopherol form), provides 1.49 IU of δ-α-tocopherol, while 1 mg of synthetic vitamin E, the all-rac-α-tocopherol form, provides 1.10 IU of dl-alpha-tocopherol. Synthetic vitamin E is inferior in comparison to natural vitamin E, with 1,000 mg of vitamin E providing 1500 IU and 1,000mg providing 1,100 IU respectively. The therapeutic dose ranges from 100 to 2000 IU per day.

Increased dietary consumption of unsaturated fat requires an increased intake of vitamin E. An increased vitamin E intake of 0.4 mg for each gram of linoleic acid and of 3-4 mg for each gram of eicosapentaenoic and docosahexaenoic acids (EPA and DHA) appear to be reasonable. As the concentration of polyunsaturated fatty acids in the diet increases, it is commonly acknowledged that the requirement for vitamin E increases. Nevertheless, a cross over trial has found that 400 mg α-tocopheryl acetate failed to change the small, but statistically significant, increase in oxidative stress reflected in plasma TBARS concentration after consuming fish oil with 2.5g EPA and 1.8g DHA daily (source). However, for those persons on a diet that is rich in polyunsaturated fatty acids, it may be untimely to halt vitamin E supplementation. A useful formula to consider is to supplement 0.4 mg of vitamin E for each gram of linoleic acid and 3-4 mg for each gram of EPA or DHA. Infants receiving a formula that is high in polyunsaturated fatty acids should be supplemented with at least 15-25 IU vitamin E each day or be given 7 IU of vitamin E for every 32 ounces of formula. Always store vitamin E supplements away from heat, damp areas and direct light.

Toxicity/Drug Interactions

The cost and safety profile of vitamin E favors empiric use in recommended doses (source). Within a therapeutic range of 200-1600 α-tocopherol equivalents, animal experiments have shown that vitamin E is not mutagenic, teratogenic or carcinogenic. Vitamin E is regarded as safe at levels up to 800 IU/day, and probably safe at doses of 1,600 IU/day. However, side effects may be expected to begin at doses of around 1,500 IU/day (source), even doses as high as 3,200 mg/day have been shown to be without any consistent risk (source). Nonetheless, some persons consuming vitamin E in doses greater than 400 IU daily over prolonged periods may experience blurred vision, diarrhea, dizziness, headache, nausea or stomach cramps, unusual tiredness, or weakness. Vitamin E decreases platelet adhesion and, at levels above 400 IU daily, may increase clotting times (source) Oral intake of high levels of vitamin E can exacerbate the blood coagulation defect of vitamin K deficiency caused by malabsorption or anticoagulant therapy (source). Provided the prothrombin time or international normalized ratio is tested on starting a new drug and repeated within 7 to 14 days of taking vitamin E, it is safe to use in combination with anticoagulants. Vitamin E, by antagonizing vitamin K and inhibiting prothrombin production, may increase risk of hemorrhagic strokes (source). Vitamin E has a number of nutrient-nutrient and nutrient-drug interactions. Vitamin E supplementation may impair the hematologic response to iron and should be avoided in iron deficiency anemia. Large doses of iron or copper may increase the requirement for vitamin E, while zinc deficiency reduces vitamin E plasma levels. The tocopherol radical can interact with vitamin C to restore tocopherol. On one hand, vitamin C has a sparing effect on vitamin E, and moderate doses of vitamin E have a sparing effect on vitamin A (source). On the other hand, large doses of vitamin E may deplete vitamin A and increase the requirement for vitamin K. Vitamin E may enhance the anti-inflammatory effect of aspirin and decrease the dose of anticoagulant, insulin, and digoxin required. Anti-convulsants, oral contraceptives, sucralfate, colestyramine, and/or liquid paraffin may reduce plasma levels of vitamin E (source).

Clinical Uses

It has been suggested that a daily intake range of 25-67 mg or 0.06-0.16 mmol vitamin E is optimal (source). A ratio of at least 1.3 to 1.5 vitamin C and E should be maintained to avoid oxidative stress. High intakes of α-tocopherol supplementation in humans have clearly shown to decrease lipid peroxidation, platelet aggregation, and that it functions as a potent anti-inflammatory agent according to epidemiologic studies (source). Vitamin E supplementation improves the immune system and offers some protection against cardiovascular disease and certain cancers (source). In all cases, doses are quoted in the units of the reference source.

Various studies suggest clinical uses of vitamin E in daily doses of the following:

  • 50-1500 mg to prevent cardiovascular disease.

  • 400 IU to reduce the risk of cataracts.

  • 20 mg for cancer prevention, increased to 50 mg daily to reduce the risk of prostate cancer in smokers. Data suggests that smoking increases the disappearance of vitamin E from the plasma. (source)

  • 800 IU in two doses of 400 IU to reverse leukoplakia or dysplasia.

  • 1600 IU for 8-12 weeks to alleviate symptoms of tardive dyskinesia. Antipsychotic (neuroleptic) medication, used to treat people with chronic mental illnesses, is associated with a suite of adverse effects, including movement disorders such as tardive dyskinesia. Small trials of uncertain quality indicate that vitamin E protects against deterioration of tardive dyskinesia, but there is no evidence that vitamin E improves symptoms (source)

  • 900 mg to reduce oxidative stress.

  • 900 mg to enhance insulin action in type 1 diabetes.

  • 60 mg in two doses of 30 mg daily to improve immune function. Immune function in the elderly improves on 800 IU/day (source).

Positive relationships between vitamin E intake and the prevention of atherosclerotic heart disease has been demonstrated in a literature search conducted between 1966 and 1999 (source). Positive outcomes such as a 77% reduction in nonfatal myocardial infarction, though there was no corresponding reduction in mortality. Two prospective cohort studies have suggested that persons taking 100-250 IU of vitamin E each day were less likely to have a major coronary event and patients with atherosclerosis on 400-800 IU of vitamin E daily were least likely to have a clinical cardiac event (source). Nevertheless, results from such studies are inconsistent. Although, basic science and animal studies have generally embraced the hypothesis that vitamin E may slow the progression of atherosclerosis. In addition, observational studies, primarily assessing patients without established coronary heart disease, have primarily supported the protective role of vitamin E. Yet initial primary and secondary prevention clinical trials have been disappointing and have failed to show a meaningful benefit from vitamin E (source). For example, a study using carotid ultrasound to evaluate atherosclerotic changes demonstrated benefit from angiotensin-converting enzyme (ACE) inhibitor, ramipril, but failed to show a difference with 400 IU of natural vitamin E. One reason for such failure may relate to the dose and isomers used. Vitamin E in doses under 50 IU/day is clinically worthless, doses over 100 IU/day may prevent or reduce the progression of coronary disease, while doses of above 1300 IU daily may be required to reduce the chance of restenosis (the recurrence of abnormal narrowing artery or valves after corrective surgery)(source).

The dose of vitamin E appears critical to its physiologic result. While doses of 400 IU α-tocopherol daily have a significant protective effect on LDL oxidation (source), at doses of 1200 IU/day, LDL oxidation is significantly greater (source). While normal plasma levels of vitamin E enhance lipoxygenation of arachidonic acid in vitro studies, yet higher concentrations have a suppressive effect (source). Daily doses of vitamin E in above 800 IU may adversely affect platelet function and 1200 IU per day may interfere with the function of vitamin K and granulocyte responses (source). Moreover, daily doses of vitamin E as high as 800 IU may enhance immunity, while doses in above 800 IU may suppress immunity. Although there currently may be insufficient evidence to recommend routine use of vitamin E for the prevention of coronary artery disease or stroke, some regard daily doses of 100-800 IU vitamin E useful for secondary prevention (source).

In addition to potentially benefiting persons with cardiovascular and cerebrovascular disease, vitamin E may assist those with peripheral vascular disease. Vitamin E is helpful for secondary prevention of intermittent claudication (pain caused by ischaemia in the muscles of the leg during exercise), providing the most benefit to those with the poorest collateral circulation and pedal blood flow (source). It could be necessary to maintain therapy for 12-18 months before benefits are observed. Doses vary for 400-1200 mg/day. However, there was insufficient evidence to determine whether vitamin E is an effective treatment for intermittent claudication in a review of clinical trials (source).

A placebo-controlled, clinical trial of 2000 IU (1342 α-tocopherol equivalents) of vitamin E per day in patients with moderately advanced Alzheimer’s disease suggested that vitamin E may slow functional deterioration (source). A double-blind, placebo-controlled, randomized, multi-center trial in patients with moderately severe Alzheimer’s disease demonstrated that α- tocopherol slows the progression of disease by 670 days (source). Vitamin E also delays the onset of memory deficits in animal models and prevents the oxidative damage induced by β-amyloid in cell culture. However, in a review of all unconfounded, double-blind, randomized trials in which treatment with vitamin E at any dose was compared with placebo (source) concluded that there was insufficient evidence for the efficacy of vitamin E in the treatment of people with Alzheimer’s disease.

Patients with type 1 diabetes should consider life-long supplementation of vitamin E. Increased vitamin E intake has been associated with enhanced glucose tolerance and insulin action (source). Pharmacologic doses of vitamin E and C increase insulin-stimulated cellular uptake of glucose. A double-blind study found that 250 IU (168 mg) of RRR-α-tocopherol taken three times/day reduced lipoprotein peroxidation in patients with type 1 diabetes (source). Type 2 diabetes has been associated with increased free radical production, lipid peroxidation, and reduced plasma vitamin E levels. The long-chain polyunsaturated fatty acid content of skeletal muscle phospholipid membranes are related to variations of insulin sensitivity.

Other likely applications for vitamin E involve incorporation as part of a more significant nutritional protocol to prevent cancer. Vitamin E inclusive protocols significantly lessen the incidence of prostate, bladder, and stomach cancers, and prevent recurrences of colonic adenomas (source). Through the stimulation of wild-type p53 tumour suppressor gene, down-regulation of mutant p53, heat shock protein activation, and an anti-angiogenic effect mediated by the blockage of transforming growth factor-alpha (TGF-α) are some of the mechanisms whereby vitamin E may impair carcinogenesis (source).

Hair Test Notes:

According to Dr Lawrence Wilson, “Vitamin E is also essential for adrenal gland activity, and for this reason, perhaps, tends to increase the oxidation or metabolic rate in all cases” (source)

Vitamin E and Selenium have a synergistic relationship (source, source) that effectively inhibit chemical carcinogens by accelerating their detoxification. Prolonged intake of selenium may cause a vitamin E deficiency and vice versa (source).

Clinical Caution

A daily intake of 4 mg vitamin E may result in a critically low plasma vitamin E level of 20-25 umol/L (30 umol/L is desirable). In reality, clinical deficiency is rare,  except in persons with fat malabsorption. A person may consume food-stuffs generally considered as sources of vitamin-E. However, these foods may cause a vitamin E deficiency (source).  Symptoms that suggest vitamin E deficiency include areflexia, psychologic syndromes, cognitive dysfunction, nystagmus, ataxia, muscle weakness, and sensory loss in the arms or legs (source). Other symptoms as a result of deficiency are lipid peroxidation, Alzheimer’s disease, infertility, menopausal symptoms, fatigue, restlessness, insomnia, anemia, creatinuria, cystic fibrosis of the pancreas, impaired circulation, general poor health, poor muscle development or muscle wasting, and asthma or other lung damage due to polluted air (source).

Practise Tips

  • To prevent deficiency, consider supplements of at least 60 mg (40.2 IU) for adult males and females, respectively.

  • Most studies suggest that the therapeutic effects of vitamin E are more likely when intake exceeds 100 IU per day, possibility 200-400 IU per day.  

  • Different antioxidants appear to act synergistically, so supplementation with vitamin E might be more effective if combined with other micronutrients.

  • Combined daily supplementation of vitamin E (200 mg) with vitamin C (1000 mg) function synergistically and enhances immunity more than either vitamin alone.

  • γ-tocopherol form of vitamin E is indicated to reduce chronic inflammation, including atherosclerosis (source).

  • Supplementation with α-tocopherol decreases tissue levels of γ-tocopherol while supplementation with γ-tocopherol increases tissue levels of both α- and γ-tocopherol.

  • At levels of 300-1000 IU, vitamin E appears free of side effects.

  • Supplementing selenium may minimise the effect of deficiency of vitamin E.

  • Muscle cramping may be eased by vitamin E (500 IU daily).

  • Dysmenorrhea may respond to 250 IU alpha-tocopherol twice daily starting ten days premenstrually and continuing for fourteen days.

  • Vitamin E and selenium protect against mercury and silver toxicity (source, source).

  • Vitamin E has anti-estrogenic effects (source,source).

Additional Reading

https://academic.oup.com/ajcn/article-abstract/8/4/451/4829432?redirectedFrom=fulltext

https://www.nrv.gov.au/nutrients/vitamin-e

http://raypeat.com/articles/articles/vitamin-e.shtml

https://www.drlwilson.com/ARTICLES/VITAMINS.htm

Chromium (Cr)

JB_MineralHealth_Chromium.jpg

Mineral Health Connection

Chromium is an essential trace mineral. In its trivalent state, it is critical for carbohydrate, lipid and nucleic acid metabolism. Chromium enhances the effects of insulin. Chromium activates phosphoglucosonetase and other enzymes.

Mechanism of action:

Chromium plays an important role in carbohydrate, fat and protein metabolism and has an impact on the expression of genes and nucleic acid synthesis.  
Insulin binding to cells seems to be increased by the presence of chromium as well as the number of insulin receptors. It activates insulin receptor kinase which increases insulin sensitivity (source). Trivalent chromium is an essential component of glucose tolerance factor. Glucose tolerance factor is believed to aid glucose transport across the cell surface as well as mediate the effects of insulin. Glucose tolerance factor also consists of two nicotinic acid molecules and a small oligopeptide, chromodulin. Chromodulin is believed to play a role in the auto-amplification of insulin signalling (source).

Food sources:

Chromium is found in various foods in quantities that correlate to the presence in the soil. It can be found in brewers yeast, cheese, molasses, wheat germ and whole grains, sugar beets, eggs, meat and seafood. Some recommend barley as a good source for chromium. Absorption of chromium is about 10%.

Dose:

A safe and adequate daily intake of chromium is between 50-200mcg. However, the therapeutic dose ranges from 200-2000mcg/day.

Clinical Uses:

Dietary sugar loads increase the natural rate of urinary chromium loss by 300% for 12 hours (source). Those with glucose intolerance such as type-1, type-2, gestational, and steroid-induced diabetes have all shown improved glucose metabolism with supplemental chromium (source). Chromium picolinate at 1,000mcg/day has had notable beneficial effects on hemoglobin A1C, glucose, insulin and cholesterol levels in those with type-2 diabetes in a clinical trial (source). It should be noted that the beneficial effects of chromium appear to only be relevant at levels which are five-fold higher than the upper limit which is supposed to be the estimated safe and adequate daily intake without any documented side-effects.

The overall requirement of chromium is relative to the degree of glucose intolerance, and while a higher intake is more effective, 200mcg of supplemental chromium is adequate to improve mild glucose intolerance in individuals. Daily intake of 8mcg/kg body weight of chromium is more effective than 4mcg/kg in women with gestational diabetes (source) and steroid-induced diabetes can be reversed with doses of 600mcg/day (source). Corticosteroids deplete chromium. A double-blind, crossover trial has confirmed that chromium supplementation improves glucose and lipid levels while decreasing medication dosage in type 2-diabetes. The results found that brewers yeast (consisting of 23.3mcg/day) was more marginally more effective than chromium chloride (200mcg/day) (source).  Preliminary observations suggest that those with a dysthymic disorder may experience symptomatic improvement within three days of treatment with chromium supplementation once or twice daily and it may enhance antidepressant therapy (source). Chromium supplementation may also be helpful for refractory mood disorders with mild side-effects (enhanced dreaming and mild psychomotor activation). The antidepressant effects of chromium have been accounted for due to the enhancement of insulin utilization and the related increases in tryptophan availability in the central nervous system, and/or by the effect of chromiums norepinephrine release (source).

Caloric restriction in athletes seeking to maintain low bodyweight compromises chromium status. Chromium has been praised as a trace element that maintains lean body mass and decreasing body fat (source), though it appears that supplementation does not promote muscle growth, strength or fat-loss in young men and women (source). Sweating from acute yet intense activity induces a short-term loss of chromium in both urine and sweat which may affect recovery days after exercise.

Significant decreases of chromium concentrations of hair, sweat and blood have been reported in age-related diseases (source).

Hair Test Notes:

Chromium concentrations in human hair is ten times greater than that found in blood. For this reason, hair tissue mineral analysis is a much more accurate representation of chromium stores in the human (there is an average of 1.5 mg in the human body under optimal conditions).

Toxicity/ Drug interactions:

At present, there is little information regarding the long-term toxicity of chromium supplements.

Not much chromium is stored in the human body; once chromium is absorbed, it is almost entirely excreted in the urine (and for this reason, urine chromium levels can be used to approximate dietary chromium status). The estimated safe and adequate daily allowance level appears to be safe and non-harmful (source). Trivalent chromium appears to have a broad safety range and no toxic effects have been reported at doses upwards of 1mg/day (source). Chromium intake excess of 100mg/day may lead to retardation of growth, cardiomyopathy, and perhaps hepatic and renal damage.

Iron and chromium compete for binding on transferrin and supplemental chromium picolinate decreases transferrin (but not chromium chloride). Chromium nicotinate or chromium picolinate has a high bioavailability. Oral hypoglycemic agents may be enhanced by chromium while reducing insulin requirements. Those that are consuming hypoglycemic agents may need to modify their dosage (source)

Vitamin C and the B vitamin niacin increase chromium absorption.  

Antacids, corticosteroids, H2 blockers (such as cimetidine, famotidine, nizatidine, and rantidine), Proton-pump inhibitors (such as omeprazole, lansoprazole, rabeprazole, pantoprazole, and esomeprazole) may inhibit chromium absorption due to alterations in stomach acidity. Whereas Beta-blockers (such as atenolol or propanolol), corticosteroids, insulin, nicotinic acid, nonsteroidal anti-inflammatory drugs (NSAIDS), or prostaglandin inhibitors (such as ibuprofen, indomethacin, naproxen, piroxicam, and aspirin) may have their effects enhanced when taken in conjunction with chromium, or increase chromium absorption (source, source, source, source)

Clinical Caution:

Assessment of dietary chromium is often problematic and suboptimal due to the absence of a reliable indicator for chromium status. Suboptimal intake of chromium is associated with risk factors for diabetes and cardiovascular diseases such as impaired glucose tolerance and metabolism, elevated circulating insulin levels, glucosuria and hyperlipidemia. The lowest normal intake of chromium has deleterious effects on glucose tolerance, insulin and glucagon levels in those with mildly impaired glucose tolerance (source). 200 mcg of chromium increased the number of insulin receptors in people with hyperglycemia. Diabetes may intensify chromium deficiency. People with type-2 diabetes lose more chromium in their urine than those who don't have diabetes. Diets with low chromium intake may have negative effects on those with borderline diabetes (source).

Diseases and Symptoms of Chromium Deficiency:

  • Low blood sugar

  • Reactive hypoglycemia

  • Bedwetting

  • Pre-diabetes

  • Diabetes (Type 2)

  • Hyperinsulinemia

  • Hyperactivity

  • Learning disability

  • ADD/ADHD

  • Hyperirritability

  • Depression

  • Manic depression

  • “Bi-polar” disease

  • Dr Jekyll/Mr. Hyde rages (“Bad Seeds”)

  • Impaired growth

  • Peripheral neuropathy

  • Negative nitrogen balance (protein/muscle loss)

  • Elevated blood triglycerides (> 200)

  • Elevated blood cholesterol (> 270)

  • Coronary artery disease

  • Aortic cholesterol plaque

  • Infertility (anovulation and low sperm count)

  • Shortened life span

  • Elevated CRP

Practice Tips:

  • Long-term chromium supplements are generally not recommended in excessive doses because the effects are unknown.

  • People who consume a diet of refined foods and high dietary sugar over prolonged periods are at risk for a chromium deficiency.

Additional Reading:

https://www.ncbi.nlm.nih.gov/pubmed/10565402

https://www.ncbi.nlm.nih.gov/pubmed/29975702

http://www.orthomolecular.org/library/jom/2000/articles/2000-v15n03-p145.shtml

http://articles.latimes.com/1992-10-20/news/mn-637_1_chromium-picolinate

Manganese (Mn)

JB_MineralHealth_Manganese.jpg

Mineral Health Connection

Manganese is an essential trace element to all known living organisms. It is an activator of several metalloenzymes, including arginase, pyruvate carboxylase, glutamine synthetase, and one form of superoxide dismutase (SOD). Manganese also functions as a non-specific enzyme activator and facilitates the synthesis of mucopolysaccharides (such as chondroitin sulfate), lipids and thyroxine. It helps prevent tissue damage caused by lipid oxidation and is an antioxidative transition metal. Manganese is part of the developmental process and the structure of the fragile ear bones.

Deficiency of this element has been induced in several animal species by feeding diets low in manganese. Signs of deficiency in animals include impaired growth, skeletal defects, depressed reproductive functions, ataxia in newborns, and defects in metabolism.

Mechanism of Action:

Manganese is an essential nutrient involved in the formation of bone and in amino acid, cholesterol, and carbohydrate metabolism. It is an enzyme activator and is a component of many metalloenzymes and may play a prominent role in calcium mobilisation. Manganese is part of the enzyme manganese superoxide dismutase and reduces the exposure to free radicals. It generates oxaloacetate, a substrate in the tricarboxylic acid (Krebs) cycle, as a constituent of pyruvate carboxylase and may play a role in glucose homeostasis. Manganese also activates enzymes that are involved in the synthesis of cartilage, facilitate the formation of urea, and activates various kinases, decarboxylases, hydroxylases and transferases.

Food sources:

Sources of manganese include; nuts, seeds and vegetables. It’s found in hazelnut, blackberries, pineapple, lentils, beans and whole grains. Due to milling, manganese content is much lower in milled whole grains. Absorption of manganese varies from 10-40%. The average body content is 0.012 g.

Dose:

Biliary secretion is the main pathway for manganese excretion (source, source). In the liver, Manganese is extracted from the blood, conjugated with bile and excreted into the intestine. A small amount of manganese in the intestine is reabsorbed, establishing an enterohepatic circulation (source) which is critical for maintaining manganese levels. The recommended intake ranges from 2.5-3mg (source). The therapeutic dose range is between 2-50mg/day.

Clinical Uses:

The control of blood sugar in diabetes and a reduction of inflammation in arthritis has been speculated of manganese.

As a component of superoxide dismutase, manganese may be useful to define therapeutic strategies for the clinical management of glioblastomas. High levels of manganese superoxide dismutase is found in patients with glioblastomas have a median survival time lower (6.11months) whereas those with low levels of this enzyme have a median survival time of 12.17 months (source). Two distinct groups of glioblastomas can be distinguished based on the content of manganese superoxide dismutase.

Toxicity/ Drug Interactions:

Oral consumption of manganese is generally non-toxic. Excessive levels of manganese found in certain community water supplies and in some industrial processes can produce a Parkinsonian syndrome or a psychiatric disorder (“locura manganica”) that resembles schizophrenia.

The clinical syndrome associated with excessive manganese and its neurodegenerative effects of manganese toxicity is known as 'Manganism' (source). However, mild inhalation of manganese could impair memory and coordination, weakness, anorexia, fatigue, depression, apathy and disturbed sleep have all been reported, irritability, hallucinations, and poor coordination have all been reported in those with manganism. Manganese in excess amounts can irreversibly damage the nervous system (source). Several clinical neurological disorders of manganism have been described as extrapyramidal motor system dysfunction and in particular idiopathic Parkinson’s disease and dystonia (source). Tremors are a critical sign of excess manganese. Despite having similar effects as the symptoms described in Parkinson's disease, the dopamine transporter activity (source).

Manganese deposits have been found in patients with biliary atresia. Possibly caused by an increase in portsystemic shunt, and latent or subclinical encephalopathy (source).

Clinical Caution:

The signs and effect of human deficiency of manganese have not been clearly established, but some potential cases in adults have shown failure in normal hair pigmentation, dermatitis, and hypocholesterolemia (source). Deficiency may cause growth impairment, tendon and bone disorders in animals but not necessarily in humans. Multiple sclerosis and Amyotrophic lateral sclerosis may have dysfunctional manganese metabolism.

Mineral Relationships

Manganese, iron, vitamin C and/or molybdenum deficiency can lead to an accumulation of copper.

Synergistic Nutrients

  • Zinc, choline, vitamin K

Antagonistic Nutrients

Absorption

  • Calcium, phosphorus, iron, soy protein.

Metabolic

  • Copper, magnesium, iron, vanadium

Practice Tips:

  • The only known reliable indicator of manganese at this time is hair tissue mineral analysis.

  • Deficiency diseases of manganese ranges from severe congenital birth defects (such as congenital ataxia, deafness, chondrodystrophy, Ehlers-danlos Syndrome etc.), allergies, asthma, convulsions, retarded growth, skeletal defects, disruption of fat and carbohydrate metabolism to joint problems (tendon and ligament degeneration, TMJ, repetitive motion syndrome, carpal tunnel syndrome, etc.), hypoglycemia, diabetes myasthenia gravis, dizziness, ringing in the ears, fatigue, muscular weakness, bone fractures or osteoporosis, weak ligaments and tendons.

Additional Reading:

https://www.crnusa.org/sites/default/files/files/resources/29-CRNVMS3-MANGANESE.pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309959/

https://www.ncbi.nlm.nih.gov/pubmed/25057538

http://www.arltma.com/Mineral_Information/Manganese.html

https://raypeatforum.com/community/threads/manganese-and-its-unimportance-in-health.22375/

http://www.traceelements.com/Docs/The%20Nutritional%20Relationships%20of%20Manganese.pdf

https://www.ncbi.nlm.nih.gov/pubmed/12711814

Iodine (I)

JB_MineralHealth_Iodine.jpg

Mineral Health Connection

Iodine is essential for red and brown algae as well as all invertebrates. The heaviest known essential trace element for humans is iodine (source). Iodine is a member of the halogen family on the periodic table of elements.

A dietary deficiency of iodine is the single most significant cause of preventable brain damage and mental retardation.

A lack of iodine is one of the most common nutritional deficiencies in the world (source).

Mechanism of action

Iodine in combination with the amino acid tyrosine link together to manufacture thyroid hormones. Thyroxine (T4) is much more abundant. However, it is not as biologically active as triiodothyronine (T3). Thyroid hormone speeds up metabolism and increases basal metabolic rate, in addition to controlling the rate of oxygen utilisation and releasing energy from energy-producing nutrients.

When there is inadequate dietary intake, plasma levels of thyroid hormones are reduced and more thyroid stimulating hormones (TSH) is released from the pituitary gland (source). If an iodine deficiency is chronic, the thyroid gland enlarges as an attempt to soak up more iodine to increase thyroid hormones. The glandular response, the stage of disease, and the concentration of thyroid hormones increasing or decreasing is dependant on the amount of iodine present. According to epidemiological studies, the primary consequence of mild to moderate iodine deficiency is hyperthyroidism, which is intricate with symptoms such as cardiac arrhythmia, osteoporosis, and muscle wasting in the elderly (source).

Iodine is a protective antioxidant that can be oxidised to hypoiodite, a potent oxidant involved in the host defence against microorganisms (source).

Food sources

The availability of iodine in foods is different depending on various regions of the world and their soil levels. Good sources for iodine include saltwater fish, seaweed, dairy products, and eggs.

Iodine can be lost during cooking, possibly as much as 70% (source). Thus, iodised salt should be added after cooking and not before or during.

Dose

Absorption of iodine is 100%. The current Recommended Daily Allowance for iodine is 110-150 mcg in adults. The levels are high for those pregnant (220 mcg) and lactating (290 mcg) respectfully (source). Supplementary dosages range between 1,000-10,000 mcg. Prolonged intake of 1,000 mcg may result in toxicosis.

Certain areas of Poland have been classified as being mild to moderately deficient in iodine. Iodine prophylaxis (a preventive protection measure aimed to avoid the health damage of individuals resulting from an accumulation of radioactive iodine in the thyroid in case of nuclear or radiation accident (source)) based only on iodised household table salt that contains 30 mg of potassium iodide per kg of salt has been highly effective (source). If iodised salt is left exposed to the air, that it will slowly lose its iodine content (source).

Many try and mimic the Japanese intake of iodine and depending on their source of information; it could be dangerous. The amount of iodine the Japanese consume daily from seaweeds has previously been estimated as high as 13.5 to 45 mg/day (source, source). Dr Lawrence Wilson suggests that the current RDA is too low and that the ideal dosage of iodine today is much higher, somewhere between 5 and 15 mg daily (source). However, a literature-based analysis estimates that the Japanese iodine intake-- mostly from seaweeds--averages 1,000-3,000 mcg per day or 1-3 mg/day (source). Thus it appears that a daily intake of 2,000 mcg (2 mg) is a safe dosage and non-toxic.

Clinical Uses:

Urinary Iodine test has revived due to the interest and growing realisation of a widespread iodine deficiency (source).

TSH should not be above 3.5, while many physicians use 5 as the upper limit of "normal" (source).

Athletes may require additional iodine as it can be excreted through sweat. Dietary iodine stores could be depleted in an athlete undergoing a regular training regime (source). In one hour of playing soccer, athletes may excrete 52 mcg, and profuse sweating may cause an iodine deficiency. This may suggest that those who have a high workload (such as an athlete), or those which are heat stressed have an increased requirement of iodine (source).

Iodine significantly increased both basal and post-stimulation TSH (source)

Our modern environment is very high in iodine antagonists such as flourine, bromine and chlorine. We quite literally bathe and swim in it! Halogens compete with one another because they look similar at the atomic level and can replace each other (source, source).

Hair Tissue Mineral Analysis Notes:

Hair appears to be a valuable biological indicator tissue for assessing long-term iodine status.

Adequate iodine status corresponds with hair iodine uptake saturation (source).

Thyroid iodine uptake is antagonised by Lead and can inactivate thyroxin (source). Flouride can inhibit thyroid hormone utilisation and interfere with iodine metabolism (source).

Mercury and copper toxicity stimulate hormone synthesis. Thyroxine (T4) requires manganese, iodine, tyrosine, cyclic AMP, vitamin C, B-complex and other micronutrients.

Low hair potassium is associated with reduced sensitivity of the mitochondrial receptors to thyroid hormone (source).

Toxicity / Drug interactions:

Excessive intake of iodine will inhibit the synthesis of thyroid hormone which can result in goitre.

In infants, an enlarged thyroid gland may obstruct their airway. It has been shown that high intakes of iodine may contribute to autoimmune hypothyroidism and that Graves’ disease can manifest at a younger age (source). Foods from the Brassica family, such as broccoli, cabbage, and turnips impair utilisation of iodine and increase dietary intake requirements.

Excessive consumption of brominated vegetable oils will deplete iodine levels. It is commonly found in citrus flavoured soda (source).

Clinical Caution

Nodules are frequently associated with Graves disease in iodine-deficient areas, and the incidence of carcinoma is high in palpable cold nodules. Iodine should be limited for clients that have graves disease. However, they generally need nutrient.

Excessive iodine intake has been linked to both hypothyroid and hyperthyroid (source, source).

It has been noted in literature that an excess of iodine can react with H202 to form free radicals that cause irreversible thyroid tissue damage (source).

Practice Tips

  • Urinary iodine reflects intake while plasma-bound iodine or thyroxine reflects function.

  • Deficiency in dietary iodine can cause low thyroid hormone production, and excess can depress thyroid function as well as cause an overactive thyroid.

Additional Reading:

https://ods.od.nih.gov/factsheets/iodine-healthprofessional/#en1

ARL : Understanding Thyroid Activity - arltma.com.

https://drlwilson.com/Articles/IODINE.htm

Boron (B)

Boron (B)

Mineral Health Connection Series

Boron compounds were known by ancient humans thousands of years ago. "Boron" was derived from the Arabic word "buraq" or the Persian word "burah", and in Sanskrit, "tincal". These are all names for Borax. 

To this day, many households still use boron in various cleaning and laundry products such as the iconic 20 Mule Team Borax laundry booster, or "Boraxo", a powdered hand soap, and can also be found in tooth whitening compounds. 

Boron is a unique elemental chemical and not a metallic mineral. Rather than being produced via stellar nucleosynthesis, boron is produced by cosmic spallation. Boron is of low abundance in both the Earth's crust and the solar system. It is concentrated on Earth by the water-solubility of more common and naturally occurring borate mineral compounds. Borate minerals are typically mined as evaporates, such as borax, boric acid, ulexite, colemanite, boracite, tourmaline, and kernite.  

Sources Of Boron

Leafy vegetables, fruits, nuts, legumes, wine, cider, beer, brown algae.

Functions In The Body

Boron is essential to life for all organisms including both plants and animals. Properties of boric acid include anti-fungal, antiseptic, and antiviral and mildly antimicrobial. Mild solutions of boric acid are used as a wound disinfectant and as an antiseptic eyewash.  Boron seems to aid in the formation of steroid hormones (estrogen) and vitamin D and estrogen and improves copper metabolism. Magnesium deficiency accentuates the effects of boron. [1][2]

Boron is required for the maintenance and metabolism of bone and normal blood levels of estrogen and testosterone; assisting both calcium [4] and magnesium in their functions. Boron is also essential for the proper function of the endocrine glands such as the ovaries, testes, and adrenals. 

  • Increases production of estrogen [4] and testosterone

  • Helps prevent osteoporosis and post-menopausal symptoms

  • May be necessary for growth (animal experiments)

  • Supportive for joints in those with osteo, rheumatoid and juvenile arthritis [5]

Within eight days of supplementing boron, women lost 40 percent less calcium, 33 percent less magnesium and less phosphorus through their urine. Women consuming boron supplementation had blood levels of estradiol 17B doubled to "levels found in women on estrogen replacement therapy,” and that levels of testosterone almost doubles in both men and women. 

The pharmaceutical, Bortezomib, a proteasome inhibitor, is used for the treatment of bone marrow cancer (multiple myeloma) and certain lymphoma. 

Symptoms Associated With A Boron Excess

Low toxicity. In animals, excessive intake affects calcium metabolism and may cause osteoporosis and increased urinary excretion of riboflavin.

In Biology, borates have low toxicity and are similar to table salt. However, it is much more toxic to insects (arthropods) and can be used as insecticides. 

Symptoms Associated With A Boron Deficiency

Osteoporosis, hot flashes and vaginal dryness in post-menopausal women.

Serine metabolism dysregulation.

Hair Analysis Notes

Significance in the hair is not apparent at this point.

Helpful with high calcium and magnesium levels due to its relationship with boron and the amino acid serine.

Research 

[1] Newnham, R.E., “‘Essentiality of Boron for Healthy Bones and joints,”‘ Environmental Health Perspectives, 102: supplement (November 1994), pp. 83-85.

[2] J Am Coll Nutr 1996 Dec;15(6):614-619

[3] Sharmin N, Hasan MS, Parsons AJ, Furniss D, Scotchford CA, Ahmed I, et al. Effect of Boron Addition on the Thermal, Degradation, and Cytocompatibility Properties of Phosphate-Based Glasses. BioMed research international. 2013;2013.

[4] Hunt CD. Dietary boron: progress in establishing essential roles in human physiology. Journal of trace elements in medicine and biology: organ of the Society for Minerals and Trace Elements (GMS). 2012; 26(2-3):157-60.

[5] Boron. Alternative Medicine Review. 2004; 9(4):434-7.

Lithium (Li)

JB_MineralHealth_Lithium.jpg

Mineral Health Connection

Lithium gets its name from the Greek word for stone, lithos because it is present in trace amounts in virtually all rocks [4]. In the human body, lithium is a trace mineral and only needed in minute quantities. Initially discovered in 1800, by the Brazilian chemist José Bonifácio de Andrada e Silva in a mine on an island in Sweden.

Major depression is far more disabling than many other diseases, including lung disease, arthritis and diabetes.. Depression is a world-wide phenomenon, happening at young and younger ages.
— Dr. Myra Weissman, psychiatric epidemiologist at Columbia University Presbyterian Medical Center in New York [3]

More than 10 million people in this country suffer from clinical depression in a given year, and two-thirds of them go undiagnosed or untreated, says Dr. Frederick Goodwin, director of the National Institute of Mental Health.

Gerhard Schrauzer, in a study relating violent crime and the drug use rate of Texas counties lithium levels in the counties drinking water:

Using date for 27 countries from 1978 to 1987, it is shown that the incidence rates of suicide, homicide, and rape are significantly higher in counties who drinking water supplies contain little or no lithium than in other counties with water levels ranging from 7-=17 ug/L;
the differences remain statistically significant (p<0.01) after corrections for population density. The corresponding associations with the incidence rates of robbery, burglary, and theft were statistically significant with p<0.05. these results suggest that lithium has moderating effects on suicidal and violent criminal behavior at levels that may be encountered in municipal water supplies. Comparisons of drinking water lithium levels in the respective Texas counties, with the incidence of arrests for possession of opium, cocaine, and their derivatives (morphine, heroin, and codeine) from 1981 to 1986 also produced statistically significant inverse associations.. [1]
— Lithium in Drinking Water and the Incidences of Crimes, Suicides, and Arrests Related to Drug Addictions [1]

Sources Of Lithium

  • Small amounts are found in a wide variety of foods

  • Lubricating grease

  • Batteries

  • Ceramics and glass

  • Used in medication to treat bipolar disorder

Dietary Sources Of Lithium

Neurotonics, functional foods that have been defined as having a nourishing and tonifying effect on the brain and nervous system, are excellent sources of Lithium such as:

  • Cacao, oats, seafood, seaweed, goji berries, various fruits and vegetables (depending on the soil in which they’re grown), and

  • egg yolks are significant sources of lithium, along with other trace minerals such as iron, copper, and manganese, which are known to co-migrate along with lithium from the soil to the plant. [2]

Functions Of Lithium

  • Decreases manic symptoms in manic-depressive patients

  • May modulate the conversion of essential fatty acids into prostaglandins

  • Anti-aggressive action

  • Correlated with the amino acid histidine

  • Stabilizes the neurotransmitter serotonin, activates glucocorticosteroid receptors and affects the production of CAMP.

Roles In The Body

  • Research by Frazier found that those patients who were helped by lithium experienced increased uptake of sodium through their cell membranes.

  • According to Sheard, lithium can replace sodium in the cells, and its structure resembles calcium and magnesium. It appears to have the same stabilising effect on nerve cells as calcium and magnesium.

Symptoms Associated With A Lithium Deficiencies

Deficiency is associated with excessive aggressiveness, manic states, depression alcohol cravings, impotence and increased suppressor cell activity.

  • Mass Murder - Austin, TX, Waco TX, Oklahoma, Columbine, Fort Hood, Virginia Tech, Batman Theater, Sandy Hook, Boston Marathon, Washington Navy Yard)

  • Serial Killers - Jack the Ripper, Boston Strangler, Jeffrey Dahmer, Green River Murderer, Michigan Old Man Stabber, etc.

  • Cannibalism

  • Domestic Violence

  • Violent Crime - Arson, Murder, Rape, Assault, Armed Robbery, etc

  • Suicide - and Suicide Bombers.

  • Signs of possible deficiency include behavioural problems,

Symptoms Associated With A Lithium Toxicity

Signs of possible deficiency include behavioural issues, depression, alcohol cravings, manic depression, impotence and increased suppressor cell activity. Disturbed mineral transport and fluid balance, nausea, vomiting, tremors, thirst, excessive urination, thyroid swelling, weight gain, drowsiness, confusion, disorientation, delirium, skin eruptions, possible kidney damage, and even seizures, coma and death.

Fluorine also has the capacity to bind to lithium in the brain. [3]

 

Hair Analysis Notes

  • Lithium appears to lower sodium levels. This would correlate with the research by A. Frazier.

  • The meaning of hair lithium levels is a topic of research.

Indications For Supplementation

Aggressive behaviour, manic-depression and some cases of depression.

 

[1] Lithium in Drinking Water and the Incidences of Crimes, Suicides, and Arrests Related to Drug Addictions GERHARD N. SCHRAUZER AND KRISHNA P. SHRESTHA

[2] Lithium as a Nutrient Timothy M. Marshall, PhD.

[3] Walters, Charles. Minerals for the Genetic Code: An Exposition & Analysis of the Dr Olree Standard Genetic Periodic Chart & the Physical, Chemical & Biological Connection (p. 10). Acres U.S.A.. Kindle Edition. 

[4] Lithium: occurrence, dietary intakes, nutritional essentiality. Schrauzer GN