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Fighting Fatigue: Iron Overload vs. Anaemia

The connections between nutrition and fatigue are many. Bill Sardi reports on the lastest state of the science.

Fatigue is a common symptom reported by up to 20 per cent of patients seeking care from primary care physicians in the US.1 According to Melvin R. Werbach, MD, a faculty member at the University of California at Los Angeles, patients should start by modifying their diets: avoid simple carbohydrates, caffeine, and sugar, and selectively use food supplements to overcome that too-common run-down feeling.2

Several common origins of fatigue may be iron or B-vitamin deficiency anaemias (red blood cell shortage); iron overload; or a shortage of nutritional co-factors involved in the production of cells' energy molecules, adenosine triphosphate (ATP).

The nutritional factors contributing to fatigue vary with age and gender. Menstruating women are more likely to feel tired because of an iron deficiency, whereas men 40 years and older are more likely to tire from iron overload.3 Poor absorption of vitamin B12 causes a high percentage of older adults to feel tired. Post-surgical patients may tire easily from blood loss (anaemia).4

Iron In The Balance
Both low and high iron levels may induce fatigue. In a European study of 6,000 people, researchers detected iron-deficiency anaemia amongst 6 per cent of the females and only .5 per cent of males, whereas they found iron overload amongst 1.8 per cent of the study population.5

Low iron levels are a common reason for women feeling tired.6 While anaemia may be understandably common among menstruating females—as prevalent as one in five women—only 2 per cent of males are anaemic. But the anaemia rate of adults older than 85 may be similarly high—ranging from 17 to 28 per cent. Anaemia in this population not only increases symptoms of fatigue but is also associated with higher mortality rates.7

Anaemia has many underlying causes. Because the body stores 80 per cent of its iron in red blood cells, blood loss can cause fatigue. Blood donation, malabsorption, menstruation, peptic ulcers and pregnancy are common causes of iron shortage and subsequent fatigue.8

Iron overload is the flip side of iron-linked fatigue. In a 1997 study in France, 42 per cent of 176 men and 64 per cent of 176 women with iron overload reported fatigue.9 In a state of iron overload, fatigue is often accompanied by arthritis, diabetes, infertility, male impotence, skin pigmentation, and liver or heart disease.10 The only reliable way to distinguish iron overload from anaemia is to conduct a blood test that measures the amount of iron being transported back to the liver, the percentage of saturation, and serum iron and ferretin levels.11

Researchers suggest high-dose iron tablets be sold by prescription because many consumers mistakenly take iron supplements when they feel fatigued.12 Because iron tablets may cause nausea and increase the risk of infection, researchers have proposed supplementary vitamin C, which increases iron absorption from foods. Plant foods contain poorly absorbed iron, whereas meat provides highly absorbed heme iron. The relatively high vitamin C content of plant foods increases iron absorption and prevents anaemia in vegetarians.13 Vitamin A and vitamin B2 (riboflavin) enhance the efficacy of iron supplementation.14

Supplemental Approaches
Because fatigue often demands a quick remedy, food supplements are often employed rather than foods alone.

  • Vitamin B12 deficiency may cause fatigue. It may initially be accompanied by indigestion or diarrhea and by short-term memory loss; sore tongue; and tingling, burning or numb feet in advanced stages. This deficiency disease is also called pernicious anaemia.15 Deficiency symptoms also include confusion, loss of vibration sensation, and walking and balance disturbances.16

    Results from a recent study conducted by the US Department of Agriculture indicates nearly two-fifths of the US adult population has marginal vitamin B12 levels.17 B12 deficiency results in fewer but larger red blood cells.

  • Coenzyme Q10 is vital for the production of cellular energy (ATP) and heart-pumping action.18 Heart failure is likely to produce symptoms of fatigue and swelling, symptoms that were evident in 37 per cent and 66 per cent, respectively, of 753 veterans treated for heart failure in a recent study.19

    The onset of a heart attack may be preceded by unusual tiredness, which may indicate a need for more Co-Q10.20 Doses of 100-255mg/day supplemental Co-Q10 have successfully reversed heart failure.21 Patients who took 200mg/day Co-Q10 showed increased heart-pumping action in one study.22 The daily provision of 200mg Co-Q10 produced universal relief from fatigue and shortness of breath among seven US patients with enlarged hearts.23 A review of 14 studies conducted between 1984 and 1994 showed that Co-Q10 increased the stroke volume and cardiac output of patients with congestive heart failure.24

  • Vitamin B6 supports natural Co-Q10 production in living tissues, so supplementing with this B vitamin and Co-Q10 is reasonable.25 Magnesium also is an essential nutrient in the production of ATP.26
  • Herbal approaches to overcome fatigue may also be beneficial, particularly because of minimal side effects. Rhodiola (Rhodiola rosea) has been reported to reduce stress-related fatigue. In a placebo-controlled, double-blind, crossover trial, low-dose treatment with a standardised extract of rhodiola reduced symptoms of fatigue in 56 young, healthy male and female physicians on night duty. Subjects in the two-week study took 170mg/day, containing approximately 4.5mg salidroside.27

In some cases, unexplained fatigue may be a physical symptom of masked depression. St. John's wort (Hypericum perforatum), 900mcg/day, was used in a small pilot study of 17 women and three men with reported depression lasting for at least two weeks. At the end of the study, only three subjects were still classified as depressed/borderline, and five as anxious/borderline.28

Fatigue often has elusive origins, but accompanying symptoms often provide clues. Nutritional factors play a primary role in fatigue resolution.

Bill Sardi is a health journalist writing from Diamond Bar, California. He is the author of The Iron Time Bomb (Bill Sardi, 1999).


1. King MS. Adrenal insufficiency: an uncommon cause of fatigue. J Am Board Fam Pract 1999;12:386-90.

2. Werbach MR. Nutritional influences on illness, 2nd ed. Tarzana (CA):Third Line Press; 1996. p 283.

3. McDonnell SM, et al. A survey of 2,851 patients with hemochromatosis: symptoms and response to treatment. Am J Med 1999 Jun;106(6):619-24.

4. Baik HW, Russell RM. Vitamin B12 deficiency in the elderly. Annu Rev Nutr 1999;19:357-77.

5. Niederau C, Christoph M. Screening for hemochromatosis and iron deficiency in employees and primary care patients in West Germany. Ann Intern Med 1998;128:337-45.

6. Patterson AJ, et al. Iron deficiency, general health and fatigue: results from the Australian Longitudinal Study on Women's Health. Quality Life Res 2000;9:491-7.

7. Izaks GJ, et al. The definition of anemia in older persons. JAMA 1999;281:1714-7.

8. Wheby M. A rational approach to the anemia workup. Patient Care 1996;30:193-7.

9. Moirand R, et al. Clinical features of genetic hemochromatosis in women compared with men. Ann Internal Med 1997;127:105-10.

10. Adams PC, et al. The relationship between iron overload, clinical symptoms, and age in 410 patients with genetic hemochromatosis. Hepatology 1997;25:162-6.

11. Martinez-Vaxquez C, et al. Prevalence of hereditary hemochromatosis among healthy workers. Diagnostic value of transferrin saturation assay. Ann Med Intern 2000;17:628-31.

12. Borch-Iohnsen B, Hauge A. Should iron preparations be available only by prescription? Tidsskr Nor Laegeforen 2001;121:460-2.

13. Sharma DC, Mathur R. Correction of anemia and iron deficiency in vegetarians by administration of ascorbic acid. Indian J Physiol Pharmacol 1995;39:403-6.

14. Fishman SM, et al. The role of vitamins in the prevention and control of anemia. Pub Health Nutr 2000;3:125-50.

15. Stabler SP. Vitamin B12 deficiency in older people: improving diagnosis and preventing disability. J Am Ger Soc 1998;46:1317-9.

16. Tucker K. B12 deficiency may be more widespread than thought. ARS News Service, USDA. 2000 Aug 2.

17. Goodman KI, Salt WB. Vitamin B12 deficiency. Important new concepts in recognition. Postgrad Med 1990;88:153-8.

18. Fuke C, et al. Coenzyme Q10: a review of essential functions and clinical trials. US Pharmacist 2000;25:1-10.

19. Evangelista LS, et al. Treatment-seeking delays in heart failure patients. J Heart Lung Transplant 2000;19:932-8.

20. Appels A. Exhausted subjects, exhausted systems. Acta Physiol Scand 1997;640:153-4S.

21. Folkers K, et al. Nutrition and cardiac health: a deficiency of coenzyme Q10 is a dominant molecular cause of heart failure. J Optimal Nut 1993;3:364-74.

22. Munkholm H, Hansen HH. Coenzyme Q10 treatment in serious heart failure. Biofactors 1999;9:285-9.

23. Langsjoen PH, et al. Treatment of hypertrophic cardiomyopathy with coenzyme Q10. Mol Aspects Med 1997;18:145-51S

24. Soja AM, Mortensen SA. Treatment of congestive heart failure with coenzyme Q10 illuminated by meta analyses of clinical trials. Mol Aspects Med 1997;18:159-68S.

25. Willis R, Anthony M. Clinical implications of the correlation between coenzyme Q10 and vitamin B6 status. Biofactors 1999;9:359-63.

26. Kisters K, et al. Importance of decreased intracellular phosphate and magnesium concentrations and reduced ATPase activities on spontaneously hypertensive rats. Magnes Res 2000;13:183-8.

27. Carbinyan V, et al. Rhodiola rosea in stress-induced fatigue—a double-blind crossover study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty. Phytomedicine 2000;7(5):365-71.

28. Stevinson C, et al. Hypericum for fatigue—a pilot study. Phytomedicine 1998;5(6):443-7.

Fighting Fatigue: Peer Review Notes

I commend Bill Sardi for his excellent article on the nutritional treatment of fatigue. Many nutrients contribute to vitality and it is important that patients be properly evaluated and treated—despite blood tests being technically in the 'normal' range.

Knowing the cause and pattern of fatigue is important. As Sardi points out, pernicious anaemia can improve with vitamin B12 alone. There are approximately 6 to 12 million Americans with chronic fatigue syndrome or a fibromyalgia-related condition, often associated with fatigue, insomnia, brain fog and diffuse achiness. It is important to treat the nutritional deficiencies, hormonal deficiencies, sleep disorder or infections such as yeast and parasites in an integrated and natural manner.

We demonstrated the effectiveness of this approach in our newly published, double-blind study. More than 85 per cent of the patients in this study improved, some dramatically.

Jacob Teitelbaum, MD, is director of the Annapolis Research Center for Effective FMS/CFS Therapies. He is the author of From Fatigued to Fantastic and senior author of "Effective Treatment of CFS and Fibromyalgia—A Placebo-controlled Study," available at

Chronic Fatigue: Its Own Entity

Chronic fatigue should be distinguished from other fatigue diagnoses. It is characterised by severe lethargy lasting at least six months, accompanied by disability and with other causes of fatigue ruled out. According to the Centers for Disease Control in Atlanta, Georgia, 2 million to 5 million people in the US have chronic fatigue syndrome; a disproportionate number are women.1

The cover story of the Nov. 12, 1990, issue of Newsweek describes chronic fatigue syndrome as a mysterious disorder that affects millions. Despite a decade of research, no single cause of this syndrome has been identified. Melvin R. Werbach, M.D., believes chronic fatigue should be challenged with an array of nutritional supplements, given the rarity of side effects and the possibility that marginal nutritional deficiencies are involved. Werbach lists B vitamins, Coenzyme Q10, essential fatty acids, L-carnitine, magnesium, vitamin C, zinc and other nutrients as worthy of a trial period.2

Patients with chronic fatigue often have shortages of various essential nutrients, including B vitamins,3 particularly vitamin B6 and folic acid.4 These patients also frequently have low blood serum levels of acetyl-L-carnitine.5

In a small study of 12 women with chronic fatigue syndrome, researchers found elevated homocysteine levels in all subjects.6 Supplemental folic acid, betaine and vitamins B6 and B12 may be helpful in reducing homocysteine levels in these cases.17

In 1994, researchers J. Alexander Brailey and Richard S. Lord reported that chronic fatigue symptoms were resolved in 75 per cent of patients after they took 15g/day of a wide range of free-form amino acid supplements for 3 months.8

Ninety per cent of patients with chronic fatigue who took omega-3 fatty acids for 3 months improved fatigue scores, with two-thirds regaining full-time duties.9 A total of 4,000mg/day of the omega-3 fatty acids linoleic, gamma linolenic, eicosapentaenoic and docosahexaenoic acids were also given to patients with prolonged post-viral fatigue syndrome, and 85 per cent reported improvement after 3 months of supplementation compared with 17 per cent of patients who received placebo.


1. Tuck I, Wallace D. Chronic fatigue syndrome: a woman's dilemma. Health Care Women Int 2000;21:457-66.

2. Werbach WR. Nutritional strategies for treating chronic fatigue syndrome. Altern Med Rev 2000;5:93-108.

3. Heap LC, et al. Vitamin B status in patients with chronic fatigue syndrome. J R Soc Med 1999;92:183-5.

4. Jacobson W, et al. Serum folate and chronic fatigue syndrome. Neurology 1993;43:2645-7.

5. Kuratsune H, et al. Low levels of serum acetylcarnitine in chronic fatigue syndrome and chronic hepatitis type C, but not seen in other diseases. Int J Mol Med 1998;2:51-6.

6. Regland B, et al. Increased concentrations of homocysteine in the cerebrospinal fluid in patients with fibromyalgia and chronic fatigue syndrome. Scand J Rheumatol 1997;26:301-7.

7. McCully KS. The Homocysteine Revolution. New Canaan (CT): Keats Publishing Inc.; 1997.

8. Brailey JA, Lord RS. Treatment of chronic fatigue syndrome with specific amino acid supplementation. J Appl Nut 1994;46:74-8.

9. Gray JB, Martinovic AM. Eicosanoids and essential fatty acid modulation in chronic disease and the chronic fatigue syndrome. Med Hypotheses 1994;43:31-42.

10. Behan PO, et al. Effect of high doses of essential fatty acids on the postviral fatigue syndrome. Acta Neurol Scand 1990;82:209-16.

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