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Omega-3 for Depression and Bipolar Disorder
Have we been fishing in all the wrong places for the magic bullet for depression and bipolar disorder? Have scientists been turning a blind eye to a well-known elixir that works well for other diseases and conditions? Ever since psychiatry threw Freud and his couch in the rubbish bin a couple of decades back, the profession has been oriented toward prescription drugs. Now, their focus appears to be widening.
In 1999, a Harvard University study generated a buzz throughout the bipolar community with the prospect of a natural substance that worked - fish oil. After years of being bombarded by industrial-strength pharmaceuticals and toxic salts, people with bipolar disorder and possibly depression could possibly look forward to a kinder and gentler treatment.
What We Know About Omega-3
In 1996, the Journal of the American Medical Association published a study comparing the prevalence of depression across ten nations. The survey yielded eye-opening results in showing how the lifetime and annual rates for depression vary widely from country to country (eg 1.5 in every 100 adults in Taiwan experience depression in their lifetimes while the figure is 19 for every 100 adults in Beirut). A 1998 study published in The Lancet compared this data with fish consumption, finding the higher consuming populations experienced less depression.
A 2003 study published in the American Journal of Psychiatry compared similar cross-national epidemiological data - this time involving bipolar disorder - and seafood consumption, again finding a strong correlation.
The working ingredient of fish oil is omega-3, a polyunsaturated fatty acid which is also found in certain plants such as flaxseed, pumpkin seed, and walnuts. According to Joseph Hibbeln MD of the NIH, who authored the two fish-consumption studies: "In the last century, [Western] diets have radically changed and we eat grossly fewer omega-3 fatty acids now. We also know that rates of depression have radically increased by perhaps a hundred-fold."
In a NY Times article, Dr Hibbeln noted:
Infant monkeys fed baby formula supplemented with omega-3 are stronger and more alert even at less than a week than monkeys given standard baby formula.
Depression is 60 times higher in New Zealand, where the average consumption of seafood is 40 pounds a year compared to Japan, where a person consumes nearly 150 pounds of seafood a year.
Postpartum depression is 50 times more common in countries with low levels of seafood consumption. During pregnancy, a woman’s body becomes depleted of fatty acids, which are transferred to the fetus.
Omega-3 seems to be critical to the growth and maintenance of brain cells, especially cell membranes.
When omega-3 is not available, the body uses omega-6, which produces cell membranes less able to cope with neurotransmitter traffic.
And of course the famous 1999 Harvard pilot study.
We eat far greater amounts of other damaging fatty acids. A healthy diet should provide for at least five grams daily of essential fatty acids, divided between omega-3 and omega-6.
A quick Medline search turns up several studies that show depleted omega-3 levels in the blood, cell membranes, and brains of depressed patients, suggesting that an intake of omega-3 could help reverse the process, though this has yet to be proved in large-scale clinical trials.
The Omega-3 Bipolar Disorder Study
The 1999 Harvard study that started it all was conducted on 30 patients with bipolar disorder, generally in stable condition but with a history of relapses (all had experienced bipolar episodes over the past year). All but eight of the subjects were on medications, which were left unchanged. Half the subjects were given 9.6 grams of fish oil capsules, the other half received olive oil.
Andrew Stoll MD, who conducted the study, admits the olive oil, which did not have a fishy taste, was not a perfect placebo. In one case, a person's cat actually attacked the fish oil capsules. But, as he jokingly confessed in a session at the 2000 DBSA annual conference, "you want a flawed study. That way, you get money to do another study."
The trial was supposed to go on for nine months, but was stopped after four due to its outstanding results, with the omega-3 group staying in remission significantly longer than the placebo patients. By two months, half of the placebo group had dropped out compared to two in the fish oil group. The omega-3 group actually did less well in lowering their mania scores than those taking placebos, but fared much better getting their depression down. Some patients experienced nausea, diarrhea, and fishy aftertaste, not surprising considering the high doses. Currently Dr Stoll is conducting a much larger and longer (three year) study that should conclude fairly soon. Other researchers are undertaking their own studies.
Other Omega-3 Depression and Bipolar Disorder Studies
These include:
Eicosapentaenoic acid (EPA) is one of the active ingredients of omega-3 fish oil. An Israeli study of 20 patients with major depression found that EPA resulted in "highly significant benefits" compared to a placebo by week three.
A 2001 study of 70 depressed patients who had not responded to other treatments were randomized into three groups taking different doses of refined EPA (one, two, or four grams a day) or a placebo. Six of the 52 patients on the EPA dropped out before 12 weeks. The one gram group did "dramatically better" than the placebo group, but surprisingly the two and four gram groups fared only modestly better than the placebo group. Much higher doses (eight to 10 gm/day) have been found effective in treating bipolar.
The higher dose paradox was borne out in a 2003 Stanley Foundation Bipolar Network study of 59 depressed bipolar patients, which found that those on 6 gm/day EPA did no better than those taking the placebo over four months, with CGI-BP depression scores dropping from 4.1 to 2.7 for EPA vs 3.6 to 2.7 for the placebo. A second study on 62 rapid-cycling patients produced similar results.
An NIH study tracking 14,541 women from their eighth week of pregnancy to eight months after giving birth found those who had no seafood - rich in omega-3 - had nearly twice the rate of depression as those who ate 10 ounces of fish daily, leading the authors to conclude: "Omega-3 fatty acids have beneficial health effects with no adverse side effects."
A Finnish/National Cancer Institute survey of 29,133 Finnish men, aged 50 to 69, has found that "there were no associations between the dietary intake of omega-3 fatty acids or fish consumption and depressed mood, major depressive episodes, or suicide."
A 2003 Chinese study of 28 patients with major depression found that those taking 9.6 grams/day of omega-3 had "a significantly decreased [Hamilton] score" after eight weeks.
More on Omega-3
The two active ingredients of omega-3 fish oil are EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). EPA is considered to be the ingredient with the therapeutic effect, so it is important to buy omega-3 that contains more EPA than DHA. A pilot study of EPA on depressed patients produced a beneficial effect while in another study DHA proved a total dud.
Fish oil has been highly touted as a prevention for heart disease and a host of other ills, so there was a ready-made supply on the market long before Dr Stoll's study.
At a seminar at the May 2004 American Psychiatric Association’s annual meeting, Jerry Cott PhD, an FDA researcher, had this to say about omega-3.
Omega-3, he said, is a fatty acid that appears to work much like a calcium channel blocker. Not uncoincidentally, he related, Joseph Hibbeln MD of the NIH, who has led the way in omega-3 research, had been working on a calcium channel blocker study. Omega-3 competes with its sister fatty acid, omega-6, for the same enzyme chain. From there, omega-3 and omega-6 are metabolized, then stored as highly unsaturated fatty acid in tissue phospholipids.. The ideal ratio of omega-6 to omega-3 is one to one, but with modern diets favoring omega-6 at 20 to one it’s fairly obvious which fatty acid is going to win the battle of the enzyme chain.
Less may also be more. Large doses may result in oxidative stress as omega-3 is being metabolized.. This may explain why some studies using EPA (see above) failed at higher doses. Accordingly, Dr Cott recommends omega-3 be taken with vitamins C and E.
Dr Stoll also recommends taking vitamins C and E with omega-3 (1.5 to 3.5 grams of omega-3 a day, taken with food). He does not suggest using cod liver oil, as high amounts can lead to hypervitaminosis A. In buying fish oil, make sure you receive a 90 percent concentration (in the past only 30 percent was available.) Be sure it contains more EPA than DHA, and that it has no heavy metal concentrations.
Dr Stoll recommends fish oil capsules over a diet of cold water fish such as salmon or tuna, citing toxic ingredients as a reason for not going with fish. Even one can of tuna a week is too much, he asserts. Andrew Weil MD - the natural health guru recommends eating fish twice or three times a week, and cautions against capsules that may contain toxic contaminants. Both doctors agree that any fish you eat should be ocean fish rather than farm-raised fish. This is because omega-3 travels up the food chain from algae, while farm-raised fished are fed grains, which do not contain omega-3.
Dr Stoll also favors fish oil over flaxseed oil, as fish oil is more proven at this point. Dr Weil says it's okay to go with flaxseed oil, which will make vegetarians happy.
Flax
An article in the Minneapolis Star Tribune waxes eloquent on the benefits of flax, which is rich in omega-3. The Emperor Charlemagne was such a great fan of the grain that he required his subjects to eat it. Ground flax seed can be sprinkled on yogurt and a dash of flax oil can fortify a smoothie. According to the article, flax seed contains just one type of omega-3, so it is advisable to keep eating fish. Most capsules contain 1,000 mgs of flax oil, although it is not yet clear how much flax the body needs. Flax seed is also a rich source in ligands (which may prevent some hormonally-related cancers) and fibers (the oil alone does not have ligands or fiber). If you buy flax seeds, be sure they are ground or that you grind them, as the body cannot digest the seed's outer hull.
The active ingredient in flax oil is alpha-linolenic acid, which is converted to EPA and DHA in the body.
Finally
Whether as fish or flax oil, omega-3 has a blood thinning effect, but this is weaker than aspirin. Please notify your doctor before you use the two together, and stop taking if you feel any ill effects.
Finally, keep in mind that although omega-3 looks like a promising way to treat depression and bipolar disorder, there are no major clinical trials to guide us. We are barely aware of its putative efficacy, much less its optimal dosage, much less how it actually works on the brain. Accordingly, omega-3 should be considered a complement to medications rather than a replacement, and should not be taken without first consulting your doctor or psychiatrist.
Have we been fishing in all the wrong places for the magic bullet for depression and bipolar disorder? Have scientists been turning a blind eye to a well-known elixir that works well for other diseases and conditions? Ever since psychiatry threw Freud and his couch in the rubbish bin a couple of decades back, the profession has been oriented toward prescription drugs. Now, their focus appears to be widening.
In 1999, a Harvard University study generated a buzz throughout the bipolar community with the prospect of a natural substance that worked - fish oil. After years of being bombarded by industrial-strength pharmaceuticals and toxic salts, people with bipolar disorder and possibly depression could possibly look forward to a kinder and gentler treatment.
What We Know About Omega-3
In 1996, the Journal of the American Medical Association published a study comparing the prevalence of depression across ten nations. The survey yielded eye-opening results in showing how the lifetime and annual rates for depression vary widely from country to country (eg 1.5 in every 100 adults in Taiwan experience depression in their lifetimes while the figure is 19 for every 100 adults in Beirut). A 1998 study published in The Lancet compared this data with fish consumption, finding the higher consuming populations experienced less depression.
A 2003 study published in the American Journal of Psychiatry compared similar cross-national epidemiological data - this time involving bipolar disorder - and seafood consumption, again finding a strong correlation.
The working ingredient of fish oil is omega-3, a polyunsaturated fatty acid which is also found in certain plants such as flaxseed, pumpkin seed, and walnuts. According to Joseph Hibbeln MD of the NIH, who authored the two fish-consumption studies: "In the last century, [Western] diets have radically changed and we eat grossly fewer omega-3 fatty acids now. We also know that rates of depression have radically increased by perhaps a hundred-fold."
In a NY Times article, Dr Hibbeln noted:
Infant monkeys fed baby formula supplemented with omega-3 are stronger and more alert even at less than a week than monkeys given standard baby formula.
Depression is 60 times higher in New Zealand, where the average consumption of seafood is 40 pounds a year compared to Japan, where a person consumes nearly 150 pounds of seafood a year.
Postpartum depression is 50 times more common in countries with low levels of seafood consumption. During pregnancy, a woman’s body becomes depleted of fatty acids, which are transferred to the fetus.
Omega-3 seems to be critical to the growth and maintenance of brain cells, especially cell membranes.
When omega-3 is not available, the body uses omega-6, which produces cell membranes less able to cope with neurotransmitter traffic.
And of course the famous 1999 Harvard pilot study.
We eat far greater amounts of other damaging fatty acids. A healthy diet should provide for at least five grams daily of essential fatty acids, divided between omega-3 and omega-6.
A quick Medline search turns up several studies that show depleted omega-3 levels in the blood, cell membranes, and brains of depressed patients, suggesting that an intake of omega-3 could help reverse the process, though this has yet to be proved in large-scale clinical trials.
The Omega-3 Bipolar Disorder Study
The 1999 Harvard study that started it all was conducted on 30 patients with bipolar disorder, generally in stable condition but with a history of relapses (all had experienced bipolar episodes over the past year). All but eight of the subjects were on medications, which were left unchanged. Half the subjects were given 9.6 grams of fish oil capsules, the other half received olive oil.
Andrew Stoll MD, who conducted the study, admits the olive oil, which did not have a fishy taste, was not a perfect placebo. In one case, a person's cat actually attacked the fish oil capsules. But, as he jokingly confessed in a session at the 2000 DBSA annual conference, "you want a flawed study. That way, you get money to do another study."
The trial was supposed to go on for nine months, but was stopped after four due to its outstanding results, with the omega-3 group staying in remission significantly longer than the placebo patients. By two months, half of the placebo group had dropped out compared to two in the fish oil group. The omega-3 group actually did less well in lowering their mania scores than those taking placebos, but fared much better getting their depression down. Some patients experienced nausea, diarrhea, and fishy aftertaste, not surprising considering the high doses. Currently Dr Stoll is conducting a much larger and longer (three year) study that should conclude fairly soon. Other researchers are undertaking their own studies.
Other Omega-3 Depression and Bipolar Disorder Studies
These include:
Eicosapentaenoic acid (EPA) is one of the active ingredients of omega-3 fish oil. An Israeli study of 20 patients with major depression found that EPA resulted in "highly significant benefits" compared to a placebo by week three.
A 2001 study of 70 depressed patients who had not responded to other treatments were randomized into three groups taking different doses of refined EPA (one, two, or four grams a day) or a placebo. Six of the 52 patients on the EPA dropped out before 12 weeks. The one gram group did "dramatically better" than the placebo group, but surprisingly the two and four gram groups fared only modestly better than the placebo group. Much higher doses (eight to 10 gm/day) have been found effective in treating bipolar.
The higher dose paradox was borne out in a 2003 Stanley Foundation Bipolar Network study of 59 depressed bipolar patients, which found that those on 6 gm/day EPA did no better than those taking the placebo over four months, with CGI-BP depression scores dropping from 4.1 to 2.7 for EPA vs 3.6 to 2.7 for the placebo. A second study on 62 rapid-cycling patients produced similar results.
An NIH study tracking 14,541 women from their eighth week of pregnancy to eight months after giving birth found those who had no seafood - rich in omega-3 - had nearly twice the rate of depression as those who ate 10 ounces of fish daily, leading the authors to conclude: "Omega-3 fatty acids have beneficial health effects with no adverse side effects."
A Finnish/National Cancer Institute survey of 29,133 Finnish men, aged 50 to 69, has found that "there were no associations between the dietary intake of omega-3 fatty acids or fish consumption and depressed mood, major depressive episodes, or suicide."
A 2003 Chinese study of 28 patients with major depression found that those taking 9.6 grams/day of omega-3 had "a significantly decreased [Hamilton] score" after eight weeks.
More on Omega-3
The two active ingredients of omega-3 fish oil are EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). EPA is considered to be the ingredient with the therapeutic effect, so it is important to buy omega-3 that contains more EPA than DHA. A pilot study of EPA on depressed patients produced a beneficial effect while in another study DHA proved a total dud.
Fish oil has been highly touted as a prevention for heart disease and a host of other ills, so there was a ready-made supply on the market long before Dr Stoll's study.
At a seminar at the May 2004 American Psychiatric Association’s annual meeting, Jerry Cott PhD, an FDA researcher, had this to say about omega-3.
Omega-3, he said, is a fatty acid that appears to work much like a calcium channel blocker. Not uncoincidentally, he related, Joseph Hibbeln MD of the NIH, who has led the way in omega-3 research, had been working on a calcium channel blocker study. Omega-3 competes with its sister fatty acid, omega-6, for the same enzyme chain. From there, omega-3 and omega-6 are metabolized, then stored as highly unsaturated fatty acid in tissue phospholipids.. The ideal ratio of omega-6 to omega-3 is one to one, but with modern diets favoring omega-6 at 20 to one it’s fairly obvious which fatty acid is going to win the battle of the enzyme chain.
Less may also be more. Large doses may result in oxidative stress as omega-3 is being metabolized.. This may explain why some studies using EPA (see above) failed at higher doses. Accordingly, Dr Cott recommends omega-3 be taken with vitamins C and E.
Dr Stoll also recommends taking vitamins C and E with omega-3 (1.5 to 3.5 grams of omega-3 a day, taken with food). He does not suggest using cod liver oil, as high amounts can lead to hypervitaminosis A. In buying fish oil, make sure you receive a 90 percent concentration (in the past only 30 percent was available.) Be sure it contains more EPA than DHA, and that it has no heavy metal concentrations.
Dr Stoll recommends fish oil capsules over a diet of cold water fish such as salmon or tuna, citing toxic ingredients as a reason for not going with fish. Even one can of tuna a week is too much, he asserts. Andrew Weil MD - the natural health guru recommends eating fish twice or three times a week, and cautions against capsules that may contain toxic contaminants. Both doctors agree that any fish you eat should be ocean fish rather than farm-raised fish. This is because omega-3 travels up the food chain from algae, while farm-raised fished are fed grains, which do not contain omega-3.
Dr Stoll also favors fish oil over flaxseed oil, as fish oil is more proven at this point. Dr Weil says it's okay to go with flaxseed oil, which will make vegetarians happy.
Flax
An article in the Minneapolis Star Tribune waxes eloquent on the benefits of flax, which is rich in omega-3. The Emperor Charlemagne was such a great fan of the grain that he required his subjects to eat it. Ground flax seed can be sprinkled on yogurt and a dash of flax oil can fortify a smoothie. According to the article, flax seed contains just one type of omega-3, so it is advisable to keep eating fish. Most capsules contain 1,000 mgs of flax oil, although it is not yet clear how much flax the body needs. Flax seed is also a rich source in ligands (which may prevent some hormonally-related cancers) and fibers (the oil alone does not have ligands or fiber). If you buy flax seeds, be sure they are ground or that you grind them, as the body cannot digest the seed's outer hull.
The active ingredient in flax oil is alpha-linolenic acid, which is converted to EPA and DHA in the body.
Finally
Whether as fish or flax oil, omega-3 has a blood thinning effect, but this is weaker than aspirin. Please notify your doctor before you use the two together, and stop taking if you feel any ill effects.
Finally, keep in mind that although omega-3 looks like a promising way to treat depression and bipolar disorder, there are no major clinical trials to guide us. We are barely aware of its putative efficacy, much less its optimal dosage, much less how it actually works on the brain. Accordingly, omega-3 should be considered a complement to medications rather than a replacement, and should not be taken without first consulting your doctor or psychiatrist.
