Mysterious syndrome linked to common imbalance in consumption of omega-3 and omega-6 fatty acids, and to low levels of zinc

by Craig Weatherby

Thanks to innovative research from Belgium, there may be new hope for alleviating the mysterious, generally un-treatable “psycho-neuro-immunological” condition known as Chronic Fatigue Syndrome (CFS).

For decades, sufferers were ignored or dismissed as hypochondriacs, which served only to worsen the depression that often accompanies the condition. Then, various viruses were blamed, before research refuted those claims.

Now the baffling syndrome has at least received official recognition of its reality and characteristic contours. In 1994, an international panel of CFS research experts convened to draft a definition of CFS. They agreed that in order to receive a diagnosis of CFS, a patient must satisfy two criteria:

  • Suffer severe chronic fatigue for six months or longer that cannot be attributed to other known medical conditions.
  • Show four or more of the following symptoms at the same time: substantial impairment in short-term memory or concentration; sore throat; tender lymph nodes; muscle pain; multi-joint pain without swelling or redness; headaches of a new type, pattern or severity; un-refreshing sleep; and post-exercise malaise lasting more than 24 hours. The symptoms must have persisted or recurred during six or more consecutive months of illness and must not have predated the fatigue.

Last December, researchers at the Clinical Research Center for Mental Health in Antwerp, Belgium published findings that may hold hope for CFS sufferers.

Omega-3 shortage, and omega-3/omega-6 imbalance in CFS sufferers

The Belgian team knew that depression and CFS often go together, and that depression often correlates with low blood levels of omega-3s.

Thinking that CFS may be related to a shortage of omega-3s, they recruited 22 CFS patients experiencing symptoms of varying severity, and 12 healthy controls, and analyzed the amounts and ratios of polyunsaturated fatty acids in these subjects' blood.

Is it really CFS?

According to the US Centers for Disease Control and Prevention, there are many treatable illnesses that can result in fatigue, and a doctor's diagnosis of any of these would exclude a diagnosis of CFS unless the condition has been treated sufficiently and no longer explains the fatigue and other symptoms.

Treatable illnesses that also feature fatigue include hypothyroidism, sleep apnea and narcolepsy, major depressive disorders, chronic mononucleosis, bipolar affective disorders, schizophrenia, eating disorders, cancer, autoimmune disease, hormonal disorders, sub-acute infections, obesity, alcohol or substance abuse, and reactions to prescribed medications.

They were looking for abnormalities and extreme imbalances in the amounts of anti-inflammatory omega-3 essential fatty acids (EFAs) and pro-inflammatory omega-6 EFAs. And their findings confirmed their suspicion that EFA imbalances might play a role in CFS:

  • All of the CFS patients had high blood levels of inflammatory omega-6 essential fatty acids (EFAs), in the form of linoleic acid (LA) and arachidonic acid (AA).
  • The ratios of omega-3 EFAs to omega-6 EFAs were significantly lower in CFS patients than in the healthy controls.
  • The ratio of one key omega-3 (EPA) to one key omega-6 AA was heavily skewed in favor of the latter.
  • The CFS patients with the lowest omega-3/omega-6 ratios had the severest fatigue and displayed more of the negative signs found on the diagnostic FibroFatigue scale, such as aches and pain, fatigue, and failing memory.

Linoleic acid is the generally pro-inflammatory omega-6 EFA that dominates common cooking oils (soy, canola, corn, cottonseed, “regular” safflower), while arachidonic acid is found in animal foods and is the omega-6 EFA critical to cell membrane function. The body converts most dietary linoleic acid to arachidonic acid, which also tends to promote inflammation.

The severity of illness was also worse in the CFS patients with the highest blood levels of linoleic and arachidonic acid, mono-unsaturated fatty acids, and the saturated fat known as palmitic acid.

As the Belgians concluded, “The results of this study show that a decreased availability of omega-3 PUFAs plays a role in the pathophysiology [underlying elements] of CFS and is related to the immune pathophysiology of CFS. The results suggest that patients with CFS should respond favorably to treatment withamongst other things—omega-3 PUFAs, such as EPA and DHA.”

When they said, “a decreased availability of omega-3 PUFAs plays a role in the pathophysiology [underlying elements] of CFS…” this means that (point underlined for emphasis) even if a CFS patient consumes what would normally be an adequate amount of dietary omega-3s, a dietary excess of omega-6 EFAs can cause them to suffer a functional deficiency of omega-3s.

This is because both categories of essential fatty acids—omega-3s and omega-6s—compete for inclusion in the same “delta-6-desaturase” metabolic pathway, so an overabundance of one will cause a functional shortage of the other.

Needless to say, these findings must be tested in placebo-controlled clinical trials before we can be sure that changes in patients' dietary fat intake will yield therapeutic benefits.

However, these results suggest that if you are diagnosed with CFS, it makes sense to get a blood test to determine your fatty acid status. And if a blood test shows the same sort of imbalance the Belgians saw in CFS patients, it would make sense to cut way back on standard cooking oils—and the packaged and restaurant foods filled with them—and to increase your intake of fatty fish and fish oil.

The average American suffers from an extreme imbalance in their intake of these two kinds of fatty acid, thanks to the overabundance of omega-6-rich vegetable oils in packaged and restaurant foods (soy, canola, corn, cottonseed, “regular safflower”), and their low intake of fish and fish oil. It may be that some of us are genetically susceptible to acquiring CFS in the context of this imbalance.

For preventive health reasons, expert US and international scientific panels recommend that adults take fish oil supplements daily. (Two capsules of our Sockeye Salmon Oil contain 320 mg of the two key omega-3s—EPA and DHA—respectively.) For details on the experts' differing intake recommendations for men and women, see “How Much Sockeye Salmon Oil Should I Take?”.

Omega-3s, zinc and oxidation in CFS

The Belgians also found a significant correlation between the imbalanced omega-3/omega-6 ratio in CFS patients' blood and low blood levels of zinc. This zinc deficiency may have been responsible for the indications of defects in “early T cell activation”—a marker of immune function—they recorded.

A more recent study by two of the same researchers (Maes M 2006) found that CFS patients had low blood levels of zinc, which was related to the same signs of immune function defects.

This finding suggests that zinc may be an important aid in treating CFS. As they said, “Since zinc is a strong anti-oxidant, the present results further support the findings that CFS is accompanied by increased oxidative stress. The results of these reports suggest that some patients with CFS should be treated with specific antioxidants, including zinc supplements.”

The current Reference Daily Intake (RDI) for zinc is 15 mg per day, and the safe upper intake limit is 40 mg per day. The RDI is the value established by the Food and Drug Administration for use in nutrition labeling. It was based initially on the highest 1968 Recommended Dietary Allowance (RDA) for each nutrient, to assure that needs were met for all age groups.


  • Maes M, Mihaylova I, Leunis JC. 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. Neuro Endocrinol Lett. 2005 Dec;26(6):745-51.
  • Maes M, Mihaylova I, De Ruyter M. Lower serum zinc in Chronic Fatigue Syndrome (CFS): relationships to immune dysfunctions and relevance for the oxidative stress status in CFS. J Affect Disord. 2006 Feb;90(2-3):141-7. Epub 2005 Dec 9.
  • Maes M, Christophe A, Delanghe J, Altamura C, Neels H, Meltzer HY. Lowered omega3 polyunsaturated fatty acids in serum phospholipids and cholesteryl esters of depressed patients. Psychiatry Res. 1999 Mar 22;85(3):275-91.