Nutrition

Vitamin E

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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

Manganese (Mn)

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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)

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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.

Nourishing Life Force

Our Human body’s innate and regenerative healing capacity functions through elegant and interdependent connections.  These connections are between our cells and the microbiota that we host as a superorganism.  These two basic units of the human supraorganism, communicate, support, and promote each other's duties through teamwork and symbiotic relationships. 

The animating force is called the vital life force, and it is present in all "living beings".  In the natural arts, it is this intelligent "energy" that endeavours to maintain functional integrity and harmony. Its movements are responsible for the inherent tendency of all living beings to move forward and grow, as well as the expression of symptoms.

The natural healing force within each of us, is the greatest force in getting well
— Hippocrates, Father of Western Medicine
The secret of medicine is to distract the patient, while Nature heals itself
— Voltaire
Nature never deceives us, it is always us who deceive ourselves
— Rousseau
Allow [the] physiologic function within to manifest its own unerring potency rather than apply a blind force from without.
— William G. Sutherland DO

These quotes from history, circumscribe the vital and innate life force. It's our inner physician. Developing an understanding of the basic principles of mineral balancing, cellular communication, reciprocal teamwork and cellular polarity, will allow us to begin to support, optimize, balance, energize and restore the innate and vital life force physiology that is essential to restoring harmony and maintain our innate regenerative capacity against the forces of entropy. 

In order to fully appreciate the profound and awe inspiring innate intelligence of Nature, firstly, it is important to acknowledge that each aspect of human is a part of a whole. Whether it be the lowliest of single-celled bacteria, or the most highly complex multi-celled superorganism such as a human being, every single expression of Nature has an inherent function, purpose or dharma. This is also true for us as humans. Every single being, is a unique expression of the whole. Both part and parcel. These functions, however minute or purposeless as they may appear at the surface level, can dramatically influence on a grand scale the movements of the vital life force and its functions in response to stimuli or stressors. They can enhance or negate our innate functions, by assisting in the regeneration of stress-induced damaged organs and/or other systems of the body.

In Quantum Medicine and Integrative Nutritional Balancing, the vital life force physiology is viewed as a dynamic and conscious response to stimuli. Residing at the “vital domain". The vital domain is both non-material and nonlocal. The vital domain is where the blueprints of  innate functions of living organisms at the physical and cellular level are stored and expressed by the vital life force. This neovitalistic view of physiology imparts a holistic perspective, providing an integrated and meaningful understanding of events and signals at every known level of human functioning. 

Furthermore, Quantum Medicine and Integrative Nutritional Balancing acknowledges the various interlocking components of the vital life force physiology through “teamwork”, "communication" and "cooperation" via interdependent actions and shared physiological functions to evoke regeneration and innate healing.

Harnessing vital life force physiology, and nourishing this innate capacity greatly assists in the restoration of our regenerative capacities, health, and wholeness. In order for the cells and microbiota to thrive, it is imperative that they work together, in harmony.

Ecosystem symbiosis and symbiotic reciprocity with one another, is essential for our normal physiological functioning. As these processes become decoherent and less efficient, tissues and organs cells compose begin to function less effectively due to entropy. Thus, the body at the quantum level becomes less coherent, dynamic and adaptable to the stress of life. 

A key to honoring the vital life force, is by shifting our attention toward its profound interconnected functions.

We have to respect that the vital life force, is our inner physician. The ultimate diagnostician and healer. Increasing the awareness of vital life force malfunction is the fulcrum of ancient therapies and modern quantum medicine.

True healing comes from within, this view very decisively empowers people by allowing them to choose to take the reigns of their health destiny.

In order to have success in healing, it is critical to support and promote all the subtle components of the inner physician into a congruent, and comprehensive operational whole. This represents a departure from the fragmented, analytical, reductionist and deterministic cartesian and newtonian thinking and enables us to integrate a different frame of reference for studying the integration of living systems and their interrelationships.

Symptomatically approaching deficiencies, infections, organs, meridians, the spine, or the subtle resonance of cells, etc. does not encourage the vital life force to function effectively or efficiently, nor does this approach enhance the adaptability, to prime the body to handle stress more effectively to augment adrenal and neuron reciprocity that can be enabled to produce powerful anti-inflammatory hormones and neurotransmitters.

Instead of symptomatic approach, we must focus solely on SUPPORTING, BALANCING, OPTIMIZING, ENERGIZING & RESTORING the innate and self-regulating, self-healing abilities of our cells and microbial counterparts, to maximize metabolic activity at every known and unknown levels of human and vital life force physiology.

Defining and reducing vital life force stressors greatly assists in the maintenance of optimal health and wellbeing. Stress is not solely of emotional or perceptual origin. Environmental pollutants too, are major stressors that are taking a toll on the dynamism of the vital life force physiology by inducing and or promoting inflammation, thymic atrophy, slow wound healing, and lowered resilience.

If we do not find effective clinical ways of removing these stressors, the vital life force will remain in a constant state of stress-defense, subject to a great deal of wear and tear and perhaps heavy metal accumulation. When this happens, our body's immune system may unleash a coordinated attack on the body—damaging cell walls, and releasing pro-inflammatory chemical toxins, digesting the lining of the GI tract, and greatly diminished nourishment, detoxification and regeneration.

Untamed immunological responses allow opportunistic pathogens to exploit the bio-terrain to their own advantage. This is a classic "hallmark" or "characteristic" of diminished adrenal gland functioning, and vital life force  bioactivity. Where prolonged inflammatory states, with good intentions, harm the body and diminish its innate functions. During this overactivity, the vital life force becomes depleted and burnt-out. Leading to an inability to either adapt or shut off toxic chemistry of stress.

Very often this leads to calcification, stiffness, prolonged retracing and emotional expressions such as: sadness, despondency, anxiety, depression, and hopelessness.  All of which are unnecessary side effects of stress overload on the vital life force.

When the vital life force is weakened and overwhelmed, due to imbalances, toxins and commensal deficits, the cells that make up the body no longer sing, but rather scream

Creating miscommunication, leading to decoherent vital body and sapped energy. In addition, the immune system may attack healthy cells, such as the case in autoimmune diseases, multiple sclerosis, or cancer cells.

Typical healing reactions of the life-force are:
1) swelling (healing responses always occurs in a fluid environment), 
2) pain (caused by edema, swelling), 
3) fever and inflammation (due to the increased blood flow into the healing tissue), 
4) discharge (to expel remnants and endogenous by-products of the healing process) potentially mixed with blood (during the reconstruction of tissue capillaries break easily), 
5) night sweats (when TB-Bacteria are involved), headaches (due to swelling of the brain, edema in the organ-related brain area), and fatigue (as the autonomic nervous system experiences a prolonged state of vagotonia / chronic sympathicotonia).

Please consider that if any of these "expressions of life force" are present for multiple months, there is a "stall" in the healing process. 

Life of a Cell

Trace elements are more important than are the vitamins, in that they cannot be synthesized by living matter. Thus they are the basic spark-plugs in the chemistry of life, on which the exchanges of energy in the combustion of foods and the building of living tissues depends.
— Dr. Henry Schroeder, The Trace Elements and Man

Have a look at the wonderful orchestra that is within the cells.

This is where mineral levels and ratios on a HTMA ultimately determine physiological and cognitive performance. By optimizing our cellular functions, we optimize overall performance.

When our cells are nourished with elemental nutrients at the optimal levels and ratios, they are able to perform the infinitely complex dance of life.

The Inner Life of a Cell. Narrated with music.  3D animation illustrating the complexity of cellular interaction.

This short film was created to help explain cellular processes to students at Harvard's Department of Molecular and Cellular Biology (BioVision initiative).

Lithium, and other Elements

Jaime Lowe shares her story about how she learned that one of the simplest atoms borne from the Big Bang, Lithium held the key to her psychological function.

This podcast also include poetry inspired by the elements and some neat facts about how we are all composed of minerals. 

Micronutrients and the Mind

We give nutrients to people and they get better... 
”When people who aren’t eating very well start to feel better when getting additional nutrients in pill form, they start to make dietary changes. They don’t crave sugar and carbs as much, and we start to see improvements down the road.. 
Once they see the simple effect of the pill and the impact it can have on their behaviour, a light bulb goes on.
— Julia Rucklidge
This talk was given at a local TEDx event, produced independently of the TED Conferences. In this critically important talk, clinical psychologist Julia Rucklidge explores a range of scientific research, including her own, showing the significant role played by nutrition in mental health or illness.