April 26, 2007 — In a recent small study, older adults who had diets high in omega-6 fatty acids and low in omega-3 fatty acids had high levels of proinflammatory cytokines; this was especially true when they had coexisting depressive symptoms. These findings are published online in the March 30 Early Release issue and in the April print issue of Psychosomatic Medicine.

Lead author Janice K. Kiecolt-Glaser, PhD, from Ohio State University in Columbus, told Medscape: "The major finding here is that yes, [diet] matters, and it probably matters more in people who have high levels of depressive symptoms." She added that this study provides evidence that diet seems to be very important in the way that people respond to depression and stress, and that "diet is not just a sideline player."

The authors explain that prior studies have shown that both depression and stress can enhance the production of proinflammatory cytokines. These cytokines — including interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) — influence the onset and course of many conditions associated with aging, including cardiovascular disease, osteoporosis, and arthritis.

The group writes that in addition, the fatty acid composition of the Western diet changed "dramatically" after 1913, when refined vegetable oil, a major source of omega-6 fatty acids, entered the diet (in the form of margarine, etc), and there was also a decrease in the consumption of foods high in omega-3 fatty acid such as fish, wild game, nuts, seeds, and green, leafy vegetables. Whereas the early hunter-gatherers had a dietary omega-6:omega-3 ratio of 2:1 to 3:1, this ratio is now 15:1 to 17:1 in North America today.

It is believed that these dietary changes might be related to increases in inflammatory-related diseases, including depression and cardiovascular disease, the group writes. They also note that in a "provocative" study by Maes and colleagues published in the May 15, 2000, issue of Biological Psychiatry, students who had higher omega-6:omega-3 ratios before examinations showed larger increases in inflammatory responses when they were stressed during examinations.

The current group sought to examine the intersection of behavior, immune function, and diet, Dr. Kiecolt-Glaser said. Specifically, they investigated the relationship between depressive symptoms, the omega-6:omega-3 ratio, and serum levels of IL-6, the IL-6 soluble receptor, and TNF-α.

The researchers recruited 43 adults: 18 caregivers (who cared for spouses with Alzheimer's disease) and 25 noncaregivers. The participants had a mean age of 67 years (range, 40 - 86 years [only 1 subject younger than 50 years]). The authors chose to study an older population because proinflammatory cytokine production is increased in older individuals. They selected caregivers since they have higher levels of depressive symptoms than noncaregivers.

The participants completed a Center for Epidemiological Studies Depression Scale (CES-D) survey, which assessed the severity of their depressive symptoms. The authors measured the participants' blood levels of IL-6, IL-6 soluble receptor, TNF-α, and fatty acids.

Diet Seemed to Affect Depression-Related Inflammation

The authors found that at higher levels of depressive symptoms, as the omega-6:omega-3 ratio increased, there was a marked increase in proinflammatory cytokine levels. "In individuals with low levels of depressive symptoms, diet didn't matter much in terms of inflammation," Dr. Kiecolt-Glaser said. "But if you had higher levels of depressive symptoms and your diet was poor in terms of the relative balance in omega-6 and omega-3 fatty acids, the increases in proinflammatory cytokines IL-6 and TNF-α really escalated."

They also found that, compared with the study participants who did not have syndromal depression, the 6 participants who had depression had significantly higher omega-6:omega-3 ratios and higher levels of proinflammatory cytokines.

"Important" Preliminary Findings, Larger Study Planned

When people are stressed and depressed, diets are poorer, since people do not usually eat more fruits and vegetables, Dr. Kiecolt-Glaser noted. She added that "any way that people get more omega-3 and less omega-6 is probably good."

The group concludes, "Our findings highlight ways in which diet may enhance or inhibit depression-related inflammation among older adults. These behavior-dietary-immune interactions have important implications for both mental and physical health." The authors are beginning a larger trial to investigate this further.

Psychosom Med. 2007;69:217-224.

Clinical Context

Study Highlights

• In the current study, blood samples from 43 older adults (mean age, 66.67 years; SD, 10.09) provided data on PUFAs and TNF-α, IL-6, and IL-6 soluble receptor.
• Depressive symptoms were assessed with the CES-D.
• Results demonstrated that depressive symptoms and omega-6:omega-3 ratios worked together to enhance proinflammatory cytokines beyond the contribution provided by either variable alone.
• The amount of variance explained by the interactions alone was substantial —13% for IL-6 and 31% for TNF-α — whereas the full models accounted for 18% and 40%, respectively.
• Although predicted cytokine levels were consistent across omega-6:omega-3 ratios with low levels of depressive symptoms, as depressive symptoms increased, there were significantly higher omega-6:omega-3 ratios as well as higher TNF-α, IL-6, and IL-6 soluble receptor levels.
• 6 individuals who met the criteria for major depressive disorder had higher omega-6:omega-3 ratios and TNF-α, IL-6, and IL-6 soluble receptor levels than those who did not meet the criteria; excluding these 6 individuals reduced the variance explained by the depressive symptoms and omega-6:omega-3 ratio interaction.
• Higher levels of IL-6 soluble receptor were associated with higher omega-6:omega-3 ratios.
• Sociodemographic and health behavior variables were evaluated as potential confounders or effect modifiers: none of age, level of education, body mass index, hours of sleep prior night, or exercise were significantly correlated with cytokine levels, fatty acid levels, or depressive symptoms (all P > .18).
• Medication use and chronic health problems were also considered as potential confounders; however, no significant interactions were found.
• Limitations of this study include its cross-sectional nature and small sample size.

Pearls for Practice

• Proinflammatory cytokines have been linked to the onset and course of a spectrum of conditions, including coronary heart disease, osteoporosis, arthritis, type 2 diabetes, approximately 15% of cancers, Alzheimer's disease, and periodontal disease.
• Depression and high omega-6:omega-3 PUFA ratios lead to elevated levels of proinflammatory cytokines, enhancing the risk for inflammatory diseases.

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