Tiredness, Its Symptoms and Causes

By Irina Bright.

This article is part of our Health & Foods section

So what is tiredness? It is, indeed, a serious health issue worth paying attention to. According to some UK estimates, unexplained tiredness affects 1 in every 5 people (approx. 12 mln. people in UK), while 1 in every 10 people experience prolonged fatigue. (Ref. 1)


green grass, young grass, brown leaves Photo: Richard Tao

1. Introduction

2. Symptoms of Tiredness

3. Causes of Tiredness

4. Causes of Unexplained Tiredness

5. Causes of Chronic Fatigue Syndrome

6. Tiredness Caused by Other Conditions

7. Tiredness Caused by Toxins in the Body

8. Other Causes of Tiredness

9. Nutritional Solutions for Tiredness



1. Introduction

For millions of people around the world, tiredness is a fact of life that they have to deal with on a day-to-day basis.

For the purpose of our discussion, we will divide tiredness into 3 distinct types:

  • Unexplained tiredness,
  • Chronic fatigue syndrome, and
  • Tiredness & chronic fatigue associated with a variety of medical conditions.

We can say that unexplained tiredness is a feeling of general lack in energy & physical strength, without any obvious reasons.

Surely, many of us are familiar with it - we may often feel sub-par and we simply don't know why. We cannot explain such tiredness because adequate rest and ample calorie intake from foods don't seem to help the situation.

Chronic fatigue syndrome (CFS), on the other hand, is a much more complex, medically-defined phenomenon. It is often accompanied not only by physical weakness & energy "deficit", but also by apathy and inability to find mental strength to do things the way other people do. Crucially, chronic fatigue syndrome is characterised by long periods of physical & mental incapacity - which usually leads to its formal diagnosis.

On other occasions though, tiredness & chronic fatigue may be a symptom of an underlying medical condition, ex. diabetes, hypo-thyroidism or liver disease. In cases like that, tiredness is usually accompanied by other symptoms and should certainly be further investigated.

2. Symptoms of Tiredness

While years ago, most of information in respect of tiredness and related issues was only available from doctors and medical research magazines, the advent of internet has given millions of people a direct opportunity to provide their own accounts and personal experiences in this area.

So, our understanding of tiredness as a medical condition has certainly been expanded from: 1) existing & growing academic knowledge, and 2) thousands of individual cases that provide the basis for anecdotal evidence.

Symptoms of Unexplained Tiredness & Chronic Fatigue Symptoms

Symptoms of unexplained tiredness, as we understand it:

  • Occasional, but regular, low levels of *physical energy*,
  • Occasional, but regular, low levels of *mental fitness* that don't let a person "get up & go" without an effort,
  • Occasional, but regular, inability to pull oneself through the day in an efficient manner,
  • Occasional, but regular, feeling generally sub-par, without any specific reason,
  • Such tiredness is usually not accompanied by other symptoms,
  • Such tiredness usually lasts for short periods of time and may naturally disappear, but may also re-appear at a later time, and disappear again.

Unexplained tiredness is only unexplained because there aren't any other obvious offending factors present in a person's life, ex., excessive alcohol consumption & ongoing stress events. If these and other similar factors are present, then the resulting tiredness can be easily explained, and is not included in our definition.

While we can loosely describe symptoms of unexplained tiredness - as most people understand it, chronic fatigue syndrome is generally accepted as a medical condition.

Although this subject is open to debate, below is a list of chronic fatigue syndrome's symptoms, as defined by the US Centers for Disease Control and Prevention.

Symptoms of chronic fatigue syndrome: (Ref. 2)

  • Extreme exhaustion and sickness following physical activity or mental exertion,
  • Sleep problems,
  • Memory and concentration issues,
  • Muscle pain,
  • Joint pain (without redness or swelling),
  • Headache, tender lymph nodes in the neck or armpit, and sore throat.

These symptoms may last for 6 or more consecutive months.

Tiredness & Fatigue as a Symptom of Other Medical Conditions

Tiredness & fatigue can be a symptom of other underlying medical conditions as well. In fact, tiredness can be caused by just about any imaginable illness due to the fact that it can simply drag the whole system down.

But let's take a quick look at some common conditions that can cause fatigue:

  • Diabetes
  • Heart disease
  • Liver disease
  • Cancer
  • Underactive thyroid
  • Irritable bowel syndrome
  • Neurological disorders

Below we discuss some possible causes of all types of tiredness with a focus on nutrient deficiencies.

3. Causes of Tiredness

The focus of this article is specifically on the deficiencies of essential nutrients as potential causes for all 3 types of tiredness we have mentioned above.

Nutritional science asserts that sufficient supply of high-quality essential nutrients to the body can help improve & maintain good health. In other words, essential nutrients may also help resolve an illness that has been acquired from the environment over a person's life-time.

So, what could potentially cause tiredness from the perspective of human nutrition?

Below we have:

1. Nutrient deficiencies including:

  • Vitamin deficiencies,
  • Mineral & trace element deficiencies,
  • Deficiencies of amino acids & fatty acids, and
  • Probiotic / prebiotic deficiencies.

2. Toxins in the body including:

  • Heavy metals,
  • Chemical agricultural additives,
  • Solvents and other harmful compounds.

It is interesting to note that essential nutrients can both eliminate deficiencies AND remove toxins from the system.

Apart from that, we'll also briefly discuss other common causes of tiredness, ex. overworking.

4. Causes of Unexplained Tiredness: Nutrient Deficiencies

We argue that unexplained tiredness can be "explained", at least to a certain degree, by a number of nutrient deficiencies. We demonstrate this below, with all the available evidence from academic research & individual case studies.


cacao powder Cacao is among the richest food sources of vitamin B complex. Learn more about cacao health benefits here.

We will start with the vitamin B complex. Deficiencies in B vitamins can have wide-ranging negative effects on our systems. B vitamins are probably among the best understood compounds.

It is curious to note that symptoms of vitamin B deficiency are the first to show while deficiencies of other vitamins - ex., vitamins A, C, D or K - are not immediately obvious. (Ref. 3)

Even as far back as the 1940s, doctors knew how crucial B vitamins were for overall health. In one test, the effects on human volunteers of diets deficient in the vitamin B complex included: easy fatigue, loss of ambition & efficiency, poor appetite, insomnia, muscle pains, and anaemia. (Ref. 3)

B vitamins work as a "complex" in harmony with each other. But vitamin B12 deficiency sometimes appears to be of special significance. (Ref. 4)

A major issue with B vitamins is that they are water-soluble and aren't stored in the body for long periods of time. So they have to come in sufficient amounts from the diet as well.

We have similar issues with Vitamin C. Just like B vitamins, vitamin C is water-soluble and is rapidly excreted from the body. It has to come in sufficient amounts from the diet as the human body cannot synthesize it.

In one case study dating back to 1947, a medical professional observed how, within half an hour of receiving an injection of ascorbic acid, a patient, "instead of being weak, apathetic, and apparently dying, became alert, bright, and cheerful", thus quickly removing tiredness & associated symptoms. (Ref. 5)

This leads us to believe that vitamin C deficiency may also be one cause of unexplained tiredness.

Many vitamins are natural antioxidants.

We know that excessive action of reactive oxygen species / free radicals within the body can cause general fatigue. (Ref. 6)

We also know that antioxidants - including vitamins A, C, E and others - fight free radicals. This action is also known as "the scavenging of free radicals". As an example, vitamin E is an especially powerful antioxidant.

So, general insufficiency of such vitamins / antioxidants may yet be another cause of tiredness.

Minerals & Trace Elements

These days, a lot more attention is paid to the role of minerals & trace elements, and their importance for the healthy function of the body. Sea-based minerals are considered to be of special value - since seas & oceans contain many unique nutrients.

In a 2013 study in Taiwan, minerals found in deep ocean mineral water: magnesium, potassium and calcium, plus more than 70 trace elements, were shown to significantly accelerate recovery from physical fatigue induced by physical exercise. (Ref. 7)

Iron deficiency has traditionally been linked to general tiredness & fatigue (Ref. 8). But other, less-researched elements such as selenium and zinc are now also coming to the fore. For example, selenium and zinc deficiencies may result in tiredness, anxiety, depression, and headaches. (Ref. 9 & 10)

These several studies allow us to conclude that mineral deficiency would be another cause of tiredness.

Amino Acids & Fatty Acids

Amino acids, or proteins, are essential nutrients that catalyze metabolic reactions, in their main function as enzymes. They also perform a number of other biological functions.

The presence of amino acids within the body is crucial for healthy metabolism & energy creation.

Fatty acids, as essential nutrients, are also required for metabolism & proper muscle function.

By inference, we conclude that insufficiency of amino acids & fatty acids may result in tiredness and fatigue as well.


Just like with minerals & trace elements, probiotics are now gaining more attention as important nutrients that are vital for human health. We are continuously learning more about them, and how they can in fact help us to manage medical conditions.

Probiotics are living organisms that are believed to contribute to a favourable intestinal environment and modulate immunological functions. (Ref. 11)

One study demonstrated how probiotics effectively reversed the symptoms of tiredness in fatigued athletes. (Ref. 12)

Their deficiency within the body may then be a factor in tiredness as well.

5. Causes of Chronic Fatigue Syndrome: Nutrient Deficiencies

Chronic fatigue syndrome is a complex set of symptoms, with an overwhelming presence of tiredness & a feeling of exhaustion that "never goes away".

Probably the most frustrating thing about this condition for those diagnosed with it is the fact that nobody knows for sure what causes it. Some medical professionals even call it "chronic idiopathic fatigue", meaning that its causes are unknown / unidentified.

Many years ago, renowned biochemist Linus Pauling said that the root cause of most medical conditions can be traced down to some basic vitamin & mineral deficiencies.

We hope our analysis below will provide some clues as to the "possible origin" of chronic fatigue syndrome, from the angle of nutrient deficiencies.


Following on from *just* tiredness, we are not surprised to see that the B vitamins may be also implicated in chronic fatigue syndrome.

Vitamins B1, B3 & B12 are some nutrients that may be *at work* here.

In one case, thiamine (vitamin B1) has been successfully used to treat people with symptoms of chronic fatigue, insomnia, nausea, chest and abdominal pain, headache and fever. (Ref. 13)

Deficiency of nicotinamide (vitamin B3) and vitamin B12 have also been shown to be a complication of severe fatigue, chronic fatigue syndrome and fibromyalgia. (Ref. 14 & 15)

A 2009 retrospective study of 221 patients diagnosed with chronic fatigue syndrome showed that their serum vitamin D levels are lower than in the general UK population. The authors suggested that this may be due to their lower exposure to natural sunlight as these patients spend excessive time indoors. (Ref. 16) Another study provided further evidence that people with chronic fatigue may be deficient in vitamin D. (Ref. 17)

Oxidative stress has recently been proposed as a potential underlying factor in chronic fatigue syndrome. (Ref. 18)

This suggestion is supported by evidence that Japanese researchers collected in 2010 on the levels of vitamin E (alpha-tocopherol) in patients with chronic fatigue syndrome.

Vitamin E is a very potent, fat-soluble antioxidant that fights oxidative stress deep within the body. The researchers found that serum concentrations of alpha-tocopherol in CFS patients during the exacerbation phase were significantly lower than in healthy control subjects; but alpha-tocopherol levels were significantly higher in the same CFS patients during the remission phase. (Ref. 18)

This suggests that vitamin E deficiency may be a cause of chronic fatigue syndrome as well.

Minerals & Trace Elements

Just like with general tiredness, deficiencies of minerals & trace elements may be another underlying factor in chronic fatigue syndrome.

Magnesium deficiency comes up over and over again. Magnesium is very important for numerous biological functions. (Ref. 19)

In a study conducted by University of Southampton UK in 1991, patients with chronic fatigue syndrome were tested for magnesium deficiency and were found to have lower red cell magnesium concentrations than healthy control subjects. In a clinical trial performed as part of the same study, each of two groups of CFS patients were given either intramuscular magnesium sulphate every week for 6 weeks or placebo. Those who were given magnesium sulphate reported improved energy levels, better emotional state, and less pain. (Ref. 20)

Iron is another chemical that is often found in suboptimal amounts in patients with chronic fatigue syndrome. (Ref. 21 & 17)

Same goes for zinc. A 2006 study conducted in Belgium reported that levels of serum zinc in CFS patients were significantly lower than in healthy controls. Since zinc is a powerful anti-oxidant, this study may further support the suggestion that chronic fatigue syndrome may indeed be related to oxidative stress. (Ref. 22)

Amino Acids & Fatty Acids

We know that chronic fatigue syndrome may be somehow related to the physiological dysfunction of the brain & central nervous system. This has been recently demonstrated with electro-encephalogram tests performed on CFS patients which "confirmed a consistent pattern of brain difference in CFS". (Ref. 23)

The brain, of course, is one of the most complex structures we can think of.

Two-thirds of the human brain are made up of fatty acids - they form the very basis of this vital organ. (Ref. 24) On the other hand, amino acids perform the role of neurotransmitters without which the brain simply cannot function. (Ref. 25)

So if the brain's physiological dysfunction lies at the heart of chronic fatigue syndrome, could such dysfunction be, at least partially, associated with malabsorption, or general deficiencies, of amino acids and fatty acids in the brains of CFS patients?

There's plenty of research that may support this hypothesis.

Amino acids:

Three studies found significant reductions in the levels of glutamine, ornithine, asparagine, phenylalanine, branch chain amino acids, succinic acid and perforin in CFS patients, as compared to healthy control subjects. (Ref 26, 27 & 28)

Deficiency and malabsorption of tryptophan that is crucial for brain function has also been found in patients with chronic fatigue syndrome and fibromyalgia. (Ref. 14)

Low levels of coenzyme Q10 in patients with chronic fatigue syndrome are believed to play a role here as well. (Ref. 29)

Fatty acids:

One research review suggests that CFS patients show deficiencies of poly-unsaturated fatty acids, which may be an effect rather than the cause of the condition itself. The author suggests that treatment with fatty acids (primrose oil) combined with some vitamins (biotin, niacin, folic acid, vitamin B6, vitamin B12 and vitamin C) and minerals (selenium, zinc and magnesium) may be helpful in managing the condition. (Ref. 30)

Another study found that CFS patients had decreased levels of omega-3 poly-unsaturated fatty acids, alongside lowered levels of serum zinc and defects in T-cell activation. (Ref. 31)


Probiotics are certainly gaining more recognition for their health benefits.

In a pilot study, CFS patients that received a high dose of Lactobacillus casei bacteria every day for 2 months reported a significant improvement in emotional symptoms including a decrease in anxiety and depression. (Ref. 32)

6. Causes of Tiredness & Fatigue Induced by Other Medical Conditions: Nutrient Deficiencies

From as early as the middle of the 20th century, thanks to a number of acclaimed nutritionists, such as Max Gerson and Linus Pauling, the world started gaining more knowledge about how nutrient deficiencies can affect human health, and how properly replenished nutrition within the body can help to fight off disease.

Below is a quick overview of how many medical conditions - many of which usually have tiredness & fatigue among the symptoms - may be caused by some common nutrient deficiencies.


Vitamin A deficiency may lead to:

Cancer (Ref. 33); Liver disease & hepatitis C (Ref. 34 & 35); Vision loss (Ref. 36); Impaired gastrointestinal immunity (Ref. 37); Measles (Ref. 38).

Vitamin B deficiency may contribute to:

Cancer (Ref. 39 & 40); Neuropathy & acute motor deficit (Ref. 41); Fatigue & depression (Ref. 15); Neurological damage, funicular spinal cord disease (myelosis), hematological & neuropsychiatric disorders, depression & dementia, macrocytic anemia, hyperhomocysteinemia, stomatitis, anorexia, diarrhea, gastrointestinal disorders (Ref. 42); Recurrent pregnancy loss (Ref. 43).

Vitamin C deficiency is implicated in:

Cancer, chronic inflammation, heart disease, increased oxidative stress (Ref. 44); Scurvy, inflammation (Ref. 45).

Vitamin D deficiency:

Muscle weakness, bone fractures, infections, auto-immune diseases, heart disease, diabetes, cancer, neurocognitive dysfunction & mental illness, infertility (Ref. 46).

Vitamin E deficiency:

Cancer & impaired immunity (Ref. 47); Cardiovascular disease (Ref. 48); Cerebellar ataxia (Ref. 49); Increased oxidative stress (Ref. 50).

Minerals & Trace Elements

Deficiencies of minerals & trace elements may cause the following.

Calcium deficiency: Fibromyalgia (Ref. 51); Osteoarthritis (Ref. 52).

Magnesium deficiency: Fibromyalgia (Ref. 51); Osteoarthritis (Ref. 52).

Iron deficiency: Fibromyalgia (Ref. 51); Osteoarthritis (Ref. 52).

Selenium deficiency: Cancer (Ref. 53 & 54); Osteoarthritis (Ref. 52).

Zinc deficiency: Cardiometabolic disease (Ref. 55); Osteoarthritis (Ref. 52).

Iodine deficiency: Underactive thyroid (Ref. 56); Osteoarthritis (Ref. 52).

Manganese deficiency: Fibromyalgia (Ref. 51); Osteoarthritis (Ref. 52).

Potassium, phosphorus, boron, cobalt deficiency: Osteoarthritis (Ref. 52).

Amino Acids & Fatty Acids

Amino Acids:

Deficiencies of certain amino acids may cause the following ailments.

Tryptophan deficiency: Fibromyalgia (Ref. 57); Cancer (Ref. 58); Depression (Ref. 59).

Histidine deficiency: Fibromyalgia (Ref. 57); Cancer (Ref. 58).

Serine deficiency: Fibromyalgia (Ref. 57).

Arginine deficiency: Cancer (Ref. 60).

Glutamine deficiency: Cancer (Ref. 58).

Neurotrophins action: Cardiovascular protective action (Ref. 61).

Fatty Acids:

Fatty acids may deliver the following beneficial effects.

Monounsaturated fatty acids: Blood pressure control (Ref. 62).

Polyunsaturated fatty acids: Cancer control (Ref. 63).

Omega-3 fatty acids: Diabetes control (Ref. 64).


Probiotics may be helpful with the following conditions.

Cancer (Ref. 65); Diarrhea, irritable bowel syndrome, general immune health (Ref. 66); Liver disease (Ref. 67); Diabetes (Ref. 68); Cardioprotection against ischemia-reperfusion injury (Ref. 69).

7. Causes of Tiredness, Chronic Fatigue Syndrome & Other Medical Conditions: Toxins in the Body

The toxic weight that we acquire from the environment and carry in our bodies for years, may ultimately end up causing adverse health effects.

Below we provide some evidence that supports this statement.

Unexplained Tiredness

Exposure to Heavy metals & other toxic metals may lead to:

Mercury: Tiredness, lack of energy, loss of appetite, concentration problems, sleep disorders in children; chronic fatigue in adults (Ref. 70 & 71).

Lead: Tiredness, decreased sleep & appetite, general body ache, shoulder joint pain (Ref. 72).

Beryllium: Tiredness, weakness, breathing difficulties, anorexia (Ref. 73).

Aluminium: Fatigue, sleep disturbances, neurological symptoms (Ref. 74).

Exposure to Pesticides, Solvents & Other Chemicals may cause:

Pesticides: Tiredness, headache, dizziness, blurred vision, vomiting (Ref. 75).

Solvents: Fatigue, memory disturbances, headache (Ref. 76).

Bromide: Fatigue, difficulty with concentration, confusion, anxiousness, insomnia (Ref. 77).

Exposure to Free radicals:

Oxidative stress/free radicals: Fatigue (Ref. 78).

Chronic Fatigue Syndrome

There is a body of evidence to support the suggestion that numerous toxins may contribute to chronic fatigue syndrome.

Metals that may contribute to CFS:

Aluminium (Ref. 21); Mercury & cadmium (Ref. 79); Nickel (Ref. 80)

Pesticides, Solvents & Other Chemicals:

Insecticides (Ref. 81); Pesticides (Ref. 82); Solvents (Ref. 83)

Free radicals may be a factor in CFS too:

Oxidative damage from free radicals may result in chronic fatigue syndrome (Ref. 84 & 85).

Various Medical Conditions

Exposure to Heavy metals may lead to:

Cancer: cadmium, lead (Ref. 86); mercury, copper (Ref. 87); arsenic (Ref. 88).

Liver disease: lead, mercury (Ref. 89).

Cardiovascular disease: arsenic, lead, cadmium, mercury (Ref. 90).

Exposure to Pesticides, Solvents & Other Chemicals may lead to:

Pesticides: Respiratory problems: asthma, chronic obstructive pulmonary disease (COPD); Cardiovascular disease: atherosclerosis & coronary artery disease; Chronic nephropathies; Autoimmune diseases: systemic lupus erythematous & rheumatoid arthritis (Ref. 82).

Solvents: Cancer (Ref. 91);

General chemicals: Cancer (Ref. 92);

Particulate pollutants: Cardiovascular dysfunction (Ref. 93);

Perfumes, cleaning chemicals: Multiple chemical sensitivity (Ref. 94).

Free radicals:

Oxidative stress/free radicals: Cancer, neurodegenerative disorders (Ref. 95); Liver disease, hepatitis C (Ref. 96); Cardiovascular disease (Ref. 97).

8. Other Causes of Tiredness, Chronic Fatigue Syndrome & Medical Conditions

Having said that, there are, of course, many other factors that affect us on a daily basis and have an ultimate effect on how we feel.

Some other causes of tiredness & chronic fatigue may be:

  • Stress
  • Overworking
  • Negative thinking
  • Sedentary lifestyle
  • Too much physical exercise
  • Being overweight or underweight
  • Prescription medication / Infections
  • Excessive alcohol consumption
  • Psychological reasons such as low self-esteem and unhappy relationships.

9. Nutritional Solutions for Tiredness

Of course, our challenge is to find nutritional solutions that will deliver all the essential nutrients to the body and will help to detoxify it at the same time.

From this perspective, our best advice would be to consume as much of seaweeds and berries as possible.

Please feel free to browse around our website to learn more.

Written and researched by: Irina Bright
Original publication date:     2013
Republication date:     2020


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31. Maes M, Mihaylova I, Leunis JC (December 2005). In chronic fatigue syndrome, the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activation. Published in Neuro endocrinology letters. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pubmed/16380690

32. A Venket Rao, Alison C Bested, Tracey M Beaulne, Martin A Katzman, Christina Iorio, John M Berardi, and Alan C Logan (2009). A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Published in Gut Pathogens. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2664325

33. Shmarakov IO, Hnep NV, Marchenko MM (November - December 2011). Biochemical features of cancer cachexia under conditions of different provision with vitamin A. Published in Ukrainskii biokhimicheskii zhurnal. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pubmed/22364025

34. Venu M, Martin E, Saeian K, Gawrieh S (March 14, 2013). High prevalence of vitamin A deficiency and vitamin D deficiency in patients evaluated for liver transplantation. Published in Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pubmed/23495130

35. Bitetto D, Bortolotti N, Falleti E, Vescovo S, Fabris C, Fattovich G, Cussigh A, Cmet S, Fornasiere E, Ceriani E, Pirisi M, Toniutto P (March 2013). Vitamin A deficiency is associated with hepatitis C virus chronic infection and with unresponsiveness to interferon-based antiviral therapy. Published in Hepatology (Baltimore, Md.). Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pubmed/23213086

36. Sherry A Tanumihardjo (August 2011). Vitamin A: biomarkers of nutrition for development. Published in The American Journal of Clinical Nutrition. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142734

37. David R. Kaufman, Jaime De Calisto, Nathaniel L. Simmons, Ashley N. Cruz, Eduardo J. Villablanca, J. Rodrigo Mora, and Dan H. Barouch (August 15, 2011). Vitamin A Deficiency Impairs Vaccine-Elicited Gastrointestinal Immunity. Published in The Journal of Immunology. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3150351

38. Clea Melenotte, Philippe Brouqui, and Elisabeth Botelho-Nevers (September 2012). Severe Measles, Vitamin A Deficiency, and the Roma Community in Europe. Published in Emerging Infectious Diseases. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437709

39. Zschbitz S, Cheng TY, Neuhouser ML, Zheng Y, Ray RM, Miller JW, Song X, Maneval DR, Beresford SA, Lane D, Shikany JM, Ulrich CM (February 2013). B vitamin intakes and incidence of colorectal cancer: results from the Women's Health Initiative Observational Study cohort. Published in The American journal of clinical nutrition. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pubmed/23255571

40. Lin CC, Yin MC (August 2007). B vitamins deficiency and decreased anti-oxidative state in patients with liver cancer. Published in European journal of nutrition. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pubmed/17571208

41. D'amico A, Bertini E (2013). Metabolic neuropathies and myopathies. Published in Handbook of clinical neurology. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pubmed/23622366

42. Wolfgang Herrmann, and Rima Obeid (October 2008). Causes and Early Diagnosis of Vitamin B12 Deficiency. Published in Deutsches Artzeblatt. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2696961

43. Puri M, Kaur L, Walia GK, Mukhopadhhyay R, Sachdeva MP, Trivedi SS, Ghosh PK, Saraswathy KN (April 2013). MTHFR C677T polymorphism, folate, vitamin B12 and homocysteine in recurrent pregnancy losses: a case control study among north Indian women. Published in Journal of perinatal medicine. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pubmed/23612630

44. Frei B, Birlouez-Aragon I, Lykkesfeldt J (2012). Authors' perspective: What is the optimum intake of vitamin C in humans? Published in Critical reviews in food science and nutrition. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pubmed/22698272

45. Joris R. Delanghe, Michel R. Langlois, Marc L. De Buyzere, Na Na, Jin Ouyang, Marijn M. Speeckaert, and Mathieu A. Torck (November 2011). Vitamin C deficiency: more than just a nutritional disorder. Published in Genes and Nutrition. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197848

46. Pludowski P, Holick MF, Pilz S, Wagner CL, Hollis BW, Grant WB, Shoenfeld Y, Lerchbaum E, Llewellyn DJ, Kienreich K, Soni M (March 28, 2013). Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality-A review of recent evidence. Published in Autoimmunity reviews. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pubmed/23542507

47. Pekmezci D (2011). Vitamin E and immunity. Published in Vitamins and hormones. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pubmed/21419272

48. Dimitrios Kirmizis and Dimitrios Chatzidimitriou (September 18, 2009). Antiatherogenic effects of vitamin E: the search for the Holy Grail. Published in Vascular Health and Risk Management. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2747395

49. Ponten SC, Kwee ML, Wolters ECh, Zijlmans JC (July 2007). First case of ataxia with isolated vitamin E deficiency in the Netherlands. Published in Parkinsonism and related disorders. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pubmed/17049453

50. Michael J. Ryan, Holly J. Dudash, Megan Docherty, Kenneth B. Geronilla, Brent A. Baker, G. Gregory Haff, Robert G. Cutlip, and Stephen E. Alway (August 10, 2010). Vitamin E and C supplementation reduces oxidative stress, improves antioxidant enzymes and positive muscle work in chronically loaded muscles of aged rats. Published in Experimental Gerontology. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3104015

51. Young-Sang Kim, Kwang-Min Kim, Duck-Joo Lee, Bom-Taeck Kim, Sat-Byul Park, Doo-Yeoun Cho, Chang-Hee Suh, Hyoun-Ah Kim, Rae-Woong Park, and Nam-Seok Joo (October 2011). Women with Fibromyalgia Have Lower Levels of Calcium, Magnesium, Iron and Manganese in Hair Mineral Analysis. Published in The Journal of Korean Medical Science. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192333

52. Joy L Frestedt, Melanie Walsh, Michael A Kuskowski, and John L Zenk (2008). A natural mineral supplement provides relief from knee osteoarthritis symptoms: a randomized controlled pilot trial. Published in Nutrition Journal. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265739

53. You-Lin Qiao, Sanford M. Dawsey, Farin Kamangar, Jin-Hu Fan, Christian C. Abnet, Xiu-Di Sun, Laura Lee Johnson, Mitchell H. Gail, Zhi-Wei Dong, Binbing Yu, Steven D. Mark, and Philip R. Taylor (April 2009). Total and Cancer Mortality After Supplementation With Vitamins and Minerals: Follow-up of the Linxian General Population Nutrition Intervention Trial. Published in Journal of the National Cancer Institute. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2664089

54. Hiroshi Yasuda, Kazuya Yoshida, Mitsuru Segawa, Ryoichi Tokuda, Toyoharu Tsutsui, Yuichi Yasuda, and Shunichi Magara (September 2009). Metallomics study using hair mineral analysis and multiple logistic regression analysis: relationship between cancer and minerals. Published in Environmental Health and Preventive Medicine. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2728251

55. Meika Foster and Samir Samman (July 2012). Zinc and Regulation of Inflammatory Cytokines: Implications for Cardiometabolic Disease. Published in Nutrients. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407988

56. Pearce EN, Andersson M, Zimmermann MB (May 2013). Global iodine nutrition: where do we stand in 2013? Published in Thyroid: official journal of the American Thyroid Association. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pubmed/23472655

57. Yunus MB, Dailey JW, Aldag JC, Masi AT, Jobe PC (January 1992). Plasma tryptophan and other amino acids in primary fibromyalgia: a controlled study. Published in The Journal of rheumatology. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pubmed/1556707

58. Yohei Miyagi, Masahiko Higashiyama, Akira Gochi, Makoto Akaike, Takashi Ishikawa, Takeshi Miura, Nobuhiro Saruki, Etsuro Bando, Hideki Kimura, Fumio Imamura, Masatoshi Moriyama, Ichiro Ikeda, Akihiko Chiba, Fumihiro Oshita, Akira Imaizumi, Hiroshi Yamamoto, Hiroshi Miyano, Katsuhisa Horimoto, Osamu Tochikubo, Toru Mitsushima, Minoru Yamakado, and Naoyuki Okamoto Libing Song, Editor (2011). Plasma Free Amino Acid Profiling of Five Types of Cancer Patients and Its Application for Early Detection. Published in PLoS One. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3168486

59. Young SN (February 2013). The effect of raising and lowering tryptophan levels on human mood and social behaviour. Published in Philosophical transactions of the Royal Society of London. Series B, Biological sciences. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pubmed/23440461

60. Vissers YL, Dejong CH, Luiking YC, Fearon KC, von Meyenfeldt MF, Deutz NE (May 2005). Plasma arginine concentrations are reduced in cancer patients: evidence for arginine deficiency? Published in The American journal of clinical nutrition. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pubmed/15883440

61. ANDREA CAPORALI and COSTANZA EMANUELI (January 2009). Cardiovascular Actions of Neurotrophins. Published in Physiological Reviews. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2836529

62. Miura K, Stamler J, Brown IJ, Ueshima H, Nakagawa H, Sakurai M, Chan Q, Appel LJ, Okayama A, Okuda N, Curb JD, Rodriguez BL, Robertson C, Zhao L, Elliott P; for the INTERMAP Research Group (June 2013). Relationship of dietary monounsaturated fatty acids to blood pressure: the international study of macro/micronutrients and blood pressure. Published in Journal of hypertension. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pubmed/23572200

63. Gu Z, Wu J, Wang S, Suburu J, Chen H, Thomas MJ, Shi L, Edwards IJ, Berquin IM, Chen YQ (April 2013). Polyunsaturated Fatty Acids Affect the Localization and Signaling of PIP3/AKT in Prostate Cancer Cells. Published in Carcinogenesis. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pubmed/23633519

64. Diana P Brostow, Andrew O Odegaard, Woon-Puay Koh, Sue Duval, Myron D Gross, Jian-Min Yuan, and Mark A Pereira (August 2011). Omega-3 fatty acids and incident type 2 diabetes: the Singapore Chinese Health Study. Published in The American Journal of Clinical Nutrition. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142726

65. Yuanmin Zhu, T. Michelle Luo, Christian Jobin, and Howard A. Youngd, (October 2011). Gut Microbiota and Probiotics in Colon Tumorigenesis. Published in Cancer Letters. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3148272

66. Gregor Reid, Jana Jass, M. Tom Sebulsky, and John K. McCormick (October 2003). Potential Uses of Probiotics in Clinical Practice. Published in Clinical Microbiology Reviews. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC207122

67. Imani Fooladi AA, Mahmoodzadeh Hosseini H, Nourani MR, Khani S, Alavian SM (February 2013). Probiotic as a novel treatment strategy against liver disease. Published in Hepatitis monthly. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pubmed/23610585

68. Hsieh FC, Lee CL, Chai CY, Chen WT, Lu YC, Wu CS (April 2013). Oral administration of Lactobacillus reuteri GMNL-263 improves insulin resistance and ameliorates hepatic steatosis in high fructose-fed rats. Published in Nutrition and metabolism. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pubmed/23590862

69. Oxman T, Shapira M, Klein R, Avazov N, Rabinowitz B (August 2001). Oral administration of Lactobacillus induces cardioprotection. Published in Journal of alternative and complementary medicine (New York, N.Y.). Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pubmed/11558777

70. Stephan Bose-O'Reilly, Kathleen M. McCarty, Nadine Steckling, and Beate Lettmeier (September 2010). Mercury Exposure and Children's Health. Published in Current Problems in Pediatric and Adolescent Health Care. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3096006

71. Sae-Ron Shin and A-Lum Han (September 2012). Improved Chronic Fatigue Symptoms after Removal of Mercury in Patient with Increased Mercury Concentration in Hair Toxic Mineral Assay: A Case. Published in Korean Journal of Family Medicine. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481032

72. D'souza Sunil Herman, Menezes Geraldine, and Thuppil Venkatesh (2007). Evaluation, diagnosis, and treatment of lead poisoning in a patient with occupational lead exposure: a case presentation. Published in Journal of Occupational Medicine and Toxicology. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2000868

73. Ross G. Cooper, and Adrian P. Harrison (August 2009). The uses and adverse effects of beryllium on health. Published in Indian Journal of Occupational and Environmental Medicine. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2847329

74. Bengt Sjogren, Anders Iregren, Wolfgang Frech, Maud Hagman, Lotta Johansson, Maria Tesarz, Arne Wennberg (1996). Effects on the nervous system among welders exposed to aluminium and manganese. Published in Occupational and Environmental Medicine. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1128401/pdf/oenvmed00073-0039.pdf

75. A E Souza, T Hermann, and H U Gringer (January 1997). The guide RNA database. Published in Nucleic Acids Research. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1464129

76. Antti-Poika M (1982). Prognosis of symptoms in patients with diagnosed chronic organic solvent intoxication. Published in International archives of occupational and environmental health. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pubmed/7152705

77. Steinhoff BJ, Paulus W (July 1992). Chronic bromide intoxication caused by bromide-containing combination drugs. Published in Deutsche medizinische Wochenschrift (1946). Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pubmed/1618120

78. Sang-Yeon Suh, Woo Kyung Bae, Hong-Yup Ahn, Sung-Eun Choi, Gyou-Chul Jung, and Chang Hwan Yeom (January 2012). Intravenous Vitamin C administration reduces fatigue in office workers: a double-blind randomized controlled trial. Published in Nutrition Journal. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3273429

79. Pacini S, Fiore MG, Magherini S, Morucci G, Branca JJ, Gulisano M, Ruggiero M (September 2012). Could cadmium be responsible for some of the neurological signs and symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Published in Medical hypotheses. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pubmed/22795611

80. Marcusson JA, Lindh G, Evengrd B (May 1999). Chronic fatigue syndrome and nickel allergy. Published in Contact dermatitis. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pubmed/10344482

81. Fernndez-Sol J, Llus Padierna M, Nogu Xarau S, Munn Mas P (April 2005). Chronic fatigue syndrome and multiple chemical hypersensitivity after insecticide exposure. Published in Medicina clnica. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pubmed/15826581

82. Mostafalou S, Abdollahi M (April 2013). Pesticides and human chronic diseases: evidences, mechanisms, and perspectives. Published in Toxicology and applied pharmacology. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pubmed/23402800

83. Racciatti D, Vecchiet J, Ceccomancini A, Ricci F, Pizzigallo E (April 2001). Chronic fatigue syndrome following a toxic exposure. Published in The Science of the total environment. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pubmed/11327394

84. Qiongman Kong and Chien-liang Glenn Lin (June 2010). Oxidative damage to RNA: mechanisms, consequences, and diseases. Published in Cellular and Molecular Life Sciences. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010397

85. Michael Maes and Frank NM Twisk (2010). Chronic fatigue syndrome: Harvey and Wessely's (bio)psychosocial model versus a bio(psychosocial) model based on inflammatory and oxidative and nitrosative stress pathways. Published in BMC Medicine. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2901228

86. Mao Wang, Hong Song, Wei-Qing Chen, Ciyong Lu, Qianshen Hu, Zefang Ren, Yan Yang, Yanjun Xu, Aiming Zhong, and Wenhua Ling (2011). Cancer mortality in a Chinese population surrounding a multi-metal sulphide mine in Guangdong province: an ecologic study. Published in BMC Public Health. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112132

87. Elena A. Belyaeva, Tatyana V. Sokolova, Larisa V. Emelyanova, and Irina O. Zakharova (2012). Mitochondrial Electron Transport Chain in Heavy Metal-Induced Neurotoxicity: Effects of Cadmium, Mercury, and Copper. Published in The Scientific World Journal. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349094

88. Joseph J. Putila, and Nancy Lan Guo (2011). Association of Arsenic Exposure with Lung Cancer Incidence Rates in the United States. Published in PLoS One. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189216

89. Matt Cave, Savitri Appana, Mihir Patel, Keith Cameron Falkner, Craig J. McClain, and Guy Brock (December 2010). Polychlorinated Biphenyls, Lead, and Mercury Are Associated with Liver Disease in American Adults: NHANES 2003-2004. Published in Environmental Health Perspectives. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002193

90. Eman M. Alissa, and Gordon A. Ferns (2011). Heavy Metal Poisoning and Cardiovascular Disease. Published in Journal of Toxicology. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3168898

91. Laura S Gold, Patricia A Stewart, Kevin Milliken, Mark Purdue, Richard Severson, Noah Seixas, Aaron Blair, Patricia Hartge, Scott Davis, and Anneclaire J De Roos (June 2011). The Relationship between Multiple Myeloma and Occupational Exposure to Six Chlorinated Solvents. Published in Occupational and Environmental Journal. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3094509

92. Carpenter DO, Bushkin-Bedient S (May 2013). Exposure to chemicals and radiation during childhood and risk for cancer later in life. Published in The Journal of adolescent health: official publication of the Society for Adolescent Medicine. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pubmed/23601608

93. Timothy D. Nelin, Allan M. Joseph, Matthew W. Gorr, and Loren E. Wold (November 2011). Direct and Indirect Effects of PM on the Cardiovascular System. Published in Toxicology Letters. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248967

94. Chiara De Luca, Desanka Raskovic, Valeria Pacifico, Jeffrey Chung Sheun Thai, and Liudmila Korkina (July 2011). The Search for Reliable Biomarkers of Disease in Multiple Chemical Sensitivity and Other Environmental Intolerances. Published in International Journal of Environmental Research and Public Health. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3155329

95. Federica Sotgia, Ubaldo E Martinez-Outschoorn, and Michael P Lisanti (May 2011). Mitochondrial oxidative stress drives tumor progression and metastasis: should we use antioxidants as a key component of cancer treatment and prevention? Published in BMC Medicine. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123229

96. Ashwani K. Singal, Sarat C. Jampana, and Steven A. Weinman (November 2011). Antioxidants as Therapeutic Agents for Liver Disease. Published in Liver International. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3228367

97. R Lee, M Margaritis, KM Channon, and C Antoniades (June 2012). Evaluating Oxidative Stress in Human Cardiovascular Disease: Methodological Aspects and Considerations. Published in Current Medicinal Chemistry. Retrieved May 11, 2013 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3412204