Low omega-3 intake seen as overlapping risk factor; fish oil regarded as likely remedial aid
by Craig Weatherby

Close readers of Vital Choices (or the medical literature) know that omega-3 fatty acids play a positive role in the two big “Ds” that burden health care in America and, increasingly, abroad as well: diabetes and depression.

A recent article in the Boston Globe reported on growing evidence suggesting that each of these debilitating diseases may promote the other.

Rather than the classic chicken-or-egg quandary, this may be a case of mutually reinforcing conditions.

Key Points
  • Many people with diabetes suffer from depression, and vice versa
  • Anti-depressant drugs may worsen diabetes
  • Search for common factors focuses on stress hormone and inadequate intake of omega-3s.
Diabetes and depression: A long history of entanglement
As the Globe story said, awareness of the back-and-forth links between diabetes and depression dates back to the late 1600s, when famed British physician Thomas Willis observed that diabetes occurred more often in chronically melancholy people.

Researchers now estimate that depression occurs more frequently in people with diabetes: about one in four diabetics display some symptoms of depression and one in seven suffer from major depression.

Conversely, a Dutch team led by Dr. Frans Pouwer reported last March that the results of another evidence review led them to conclude that being depressed increases the risk of developing diabetes by 37 percent (Knol MJ et al 2006). This finding is remarkable, since it ranks depression as a diabetes risk factor comparable to smoking or lack of exercise.

And, unfortunately, many depressed diabetics get no relief from anti-depressant drugs. Last year, Dr. Pouwer's group reported that anti-depressant drugs work well in only about half of diabetics suffering from chronic sadness (Pouwer F et al 2005).

The goal of Dr. Pouwer's study was to determine whether omega-3s could alleviate both conditions. And its findings indicate that indeed, these fish-derived fatty acids may help people suffering from both diseases:
  • “Epidemiological and clinical studies suggest that a high intake of omega-3 [fatty acids] protects against the development of depression.”
  • “There is also some evidence that a low intake of omega-3 is associated with an increased risk of Type 2 diabetes...”
  • “Results from randomized controlled trials in non-diabetic subjects with major depression show that eicosapentaenoic acid [EPA, one of the two major omega-3s in fish oil] is an effective adjunct treatment of depression in diabetes...”
  • “Moreover, consumption of omega-3 [fatty acids] reduces the risk of cardiovascular disease and may therefore indirectly decrease depression in Type 2 diabetes, via the reduction of cardiovascular complications.”
  • “Supplementation with omega-3 [fatty acids] ... may be a safe and helpful tool to reduce the incidence of depression and to treat depression in Type 2 diabetes. Further studies are now justified to test these hypotheses...”
Why should depression fuel diabetes?
Scientists are beginning to uncover clues that may explain the diabetes-depression connection.

Diabetes: a tale of two types
Other than the central problem of blood sugar control, the two types of diabetes are distinctly different:
  • Type 1 develops in early childhood and is a relatively rare autoimmune disease in which the immune system destroys the pancreatic islet cells that produce insulin. Patients must receive supplemental insulin by injection as needed, or suffer a coma or death.
  • Type 2 or “adult onset” diabetes usually occurs in people of middle age or older who are overweight and sedentary: conditions that can cause their cells to become “resistant” to insulin's attempts to transport dietary sugar into cells.
Type 1 diabetes patients with a lifetime history of major depression show significantly worse blood-sugar control than their mentally healthy counterparts.

In contrast, Type 2 diabetes patients with a history of major depression did not have significantly worse control than their mentally healthy peers (de Groot M et al 1999).

Four years ago, researchers at the Joslin Diabetes Center found differences in the brains of people with and without Type 1 diabetes (Jacobson AM et al 2002). The brains of diabetics were less dense and less responsive in an area of the prefrontal cortex that helps control emotions and is involved in depression.

Other findings show that blood levels of the stress hormone cortisol are higher than normal in many people with depression. Cortisol also impairs production of insulin and increases the “insulin resistance” characteristic of Type 2 diabetes.

As Pat Lustman, a professor of psychiatry at Washington University in St. Louis told the Globe, “That [chronically elevated cortisol levels] could be the direct link”.

Earlier this year, a team led by Dr. Lustman reported that a Prozac-type anti-depressant drug called Sertraline relieved depression and improved blood-sugar control in Type 2 diabetics (Lustman PJ et al 2006).

In addition to any metabolic interplay between depression and diabetes, the benefits seen in Lustman's study may stem from the simple fact that diabetics' will to control their blood sugar via exercise and diet is enhanced when their depression is eased by drugs… or omega-3s.

And other evidence indicates there may be a dark, diabetes-promoting side to anti-depressants.

Do Prozac and company make matters worse?
The results of a three-year study reported last summer suggest that use of antidepressant drugs might promote diabetes. The study was designed to test ways to prevent diabetes in 3,000 people at high risk for the disease due to poor blood sugar control.

Contrary to the findings of many earlier studies, the participants who reported signs of depression at the outset of the study were no more likely to develop diabetes, but the subjects taking anti-depressant drugs were at greater risk.

Their key finding was that the participants taking anti-depressants along with a drug that lowers blood sugar (metformin hydrochloride) did not develop diabetes: an outcome that suggests that the anti-depressants would have worsened blood sugar control if not for the anti-diabetes drug's opposite effect.

We should note that since the study could not prove that the drugs caused diabetes, people should not abandon prescribed antidepressants unless an alternative therapy is available. (Given the strong evidence that omega-3s may alleviate depression, it makes sense for depressed diabetics to discuss nutritional therapy with their physician.)

New parts of the puzzle: Inflammation and omega-3s
Interestingly, Type 2 diabetes and depression are both characterized by increased production of pro-inflammatory immune-system proteins called cytokines. These messenger chemicals affect the brain's hypothalamus, which plays a key part in regulating mood and blood sugar levels. Researchers are testing treatments that reduce inflammation.

And Dr. Pouwer's Dutch team has been investigating the prospect that omega-3 fatty acids play a central role, since they enhance brain function and mood and help extinguish excessive inflammation.

Diets deficient in omega-3 fatty acids
such as the standard American dietare linked to depression and may reduce the body's ability to control blood sugar. Accordingly, the Dutch group plans to test whether dietary omega-3s can improve mood and reduce insulin resistance in depressed diabetics.

Last, we should note that there may be a gender difference in the diabetes-depression link. Contradicting the equivocal results of a much smaller study published the year before (Lloyd CE et al 2000), the Dutch team reported finding that women were significantly more likely to have elevated levels of a marker for poor blood sugar control (glycosylated hemoglobin), compared with men, possibly because of the effects of estrogen (Pouwer F et al 2001).

  • Knol MJ, Twisk JW, Beekman AT, Heine RJ, Snoek FJ, Pouwer F. Depression as a risk factor for the onset of type 2 diabetes mellitus. A meta-analysis. Diabetologia. 2006 May;49(5):837-45. Epub 2006 Mar 7.
  • Pouwer F, Nijpels G, Beekman AT, Dekker JM, van Dam RM, Heine RJ, Snoek FJ. Fat food for a bad mood. Could we treat and prevent depression in Type 2 diabetes by means of omega-3 polyunsaturated fatty acids? A review of the evidence. Diabet Med. 2005 Nov;22(11):1465-75. Review.
  • Adriaanse MC, Dekker JM, Nijpels G, Heine RJ, Snoek FJ, Pouwer F. Associations between depressive symptoms and insulin resistance: The Hoorn Study. Diabetologia. 2006 Dec;49(12):2874-7. Epub 2006 Oct 26.
  • Jacobson AM, Samson JA, Weinger K, Ryan CM. Diabetes, the brain, and behavior: is there a biological mechanism underlying the association between diabetes and depression? Int Rev Neurobiol. 2002;51:455-79. Review.
  • de Groot M, Jacobson AM, Samson JA, Welch G. Glycemic control and major depression in patients with type 1 and type 2 diabetes mellitus. J Psychosom Res. 1999 May;46(5):425-35.
  • Lustman PJ, Clouse RE, Nix BD, Freedland KE, Rubin EH, McGill JB, Williams MM, Gelenberg AJ, Ciechanowski PS, Hirsch IB. Sertraline for prevention of depression recurrence in diabetes mellitus: a randomized, double-blind, placebo-controlled trial. Arch Gen Psychiatry. 2006 May;63(5):521-9.
  • Pouwer F, Snoek FJ. Association between symptoms of depression and glycaemic control may be unstable across gender. Diabet Med. 2001 Jul;18(7):595-8.
  • Lloyd CE, Dyer PH, Barnett AH. Prevalence of symptoms of depression and anxiety in a diabetes clinic population. Diabet Med. 2000 Mar;17(3):198-202.
  • Dembner A. Diabetics often suffer depression. Depressed people often get diabetes. Why? Boston Globe Staff, October 30, 2006.