Therapeutic Uses
Consumption of fish oil alters the body’s production of certain substances in the class of chemicals called prostaglandins. Some prostaglandins increase inflammation while others decrease it. The prostaglandins whose production is enhanced by fish oil fall into the anti-inflammatory category. Based on this, fish oil has been tried as a treatment for early stages of
rheumatoid arthritis
, with positive results. It is thought to significantly reduce symptoms without causing side effects and may magnify the benefits of standard arthritis drugs.
37,38,179
However, while some standard medications can slow the progression of the disease, there is no evidence that fish oil can do this.
Much weaker evidence hints that fish oil might be helpful for the related disease ankylosing spondylitis.
232
Fish oil’s apparent anti-inflammatory properties are the likely explanation for its apparent benefit in
dysmenorrhea
(menstrual pain), as seen in two studies.
39,40
Similarly, fish oil may be helpful for the autoimmune disease
lupus
.
137,191
(However, two studies failed to find fish oil helpful for
kidney disease
caused by lupus.
138,139
)
Evidence has been mixed regarding whether fish oil is beneficial for
Crohn's disease
or
ulcerative colitis
, conditions in which parts of the digestive tract are highly inflamed.
49-51,61-68, 159,201
More recently, however, two well-designed trials enrolling a total of 738 patients convincingly failed to find any benefit for omega-3 fatty acid supplementations in the prevention of Crohn’s disease relapse.
254
Incomplete evidence hints but does not prove that fish or fish oil might help prevent death caused by
heart disease
.
152,202
This effect seems to result from several separate actions. The best documented involves reducing
high triglyceride levels
; studies enrolling more than 2,000 people have substantiated this use.
1
In addition, fish oil might raise HDL ("good") cholesterol levels, "thin" the blood, lower levels of
homocysteine
, prevent dangerous heart arrhythmias, slow heart rate, improve blood vessel tone, and decrease
blood pressure
.
14,15,51,90-94,96-105,151,160-165,174,177,189,190,203-204,238
These effects also support findings that fish oil may help prevent
strokes
.
20,178
However, results are conflicting on whether people with
angina
should take fish oil or increase intake of fatty fish; one large study actually found that fish oil
increased
risk of sudden death.
206
For a number of theoretical reasons, it has been suggested that fish oil and its constituents (especially a slightly modified form of EPA called ethyl-EPA) might have positive effects on various psychiatric disorders, most notably
depression
. However, there is no convincing evidence that low levels of omega-3 fatty acids in the bloodstream leads to even mild depression.
259
Moreover, larger trials have generally failed to demonstrate a beneficial effect of fish oil-related products in depressed patients.
154,168,188,192,193,207,228,234,241,242,244
Some evidence hints that high doses of fish oil may produce benefits in
bipolar disorder
, reducing risk of relapse and improving emotional state.
41,205,242,284
Other preliminary, and again not altogether consistent, evidence hints that fish oil might enhance the effectiveness of standard drugs (such as
phenothiazines
) for schizophrenia.
48,148,169,170,193,247
One trial of 81 adolescents and young adults (considered at very high risk) found that daily omega-3 fatty acid supplements for 12 weeks delayed transition to a first full-blown psychotic episode (e.g., shcizophrenia) within one year.
276
Fish oil has also shown a bit of promise for borderline personality disorder.
180
In one study, DHA failed to augment the effectiveness of standard therapy for
attention deficit disorder
(ADD).
89
However, two studies that evaluated the potential benefits of fish oil combined with
omega-6 fatty acids
found some evidence of benefit for this condition.
88,194
Finally, one small trial found evidence that use of fish oil might decrease anger and aggressiveness in people with a history of aggressive behaviors, substance abuse, and problems with the law.
243
Small studies also suggest that fish oil may be helpful in
Raynaud's phenomenon
(a condition in which a person's hands and feet show abnormal sensitivity to cold temperatures),
42,43sickle-cell anemia
,
45
and a form of kidney disease called IgA nephropathy.
47
According to some, but not all studies, fish oil may help treat the
undesired weight loss
often experienced by people with cancer.
181-182
In addition, highly preliminary evidence hints that DHA might enhance the effects of the
cancer chemotherapy
drug doxorubicin
157
and decrease side effects of the chemotherapy drug irinotecan.
158
Use of fish oil by
pregnant women
might help prevent premature birth,
184-185,208,236
although evidence is somewhat inconsistent. In addition, use of fish oil by pregnant women may support healthy brain function
183
and help prevent eczema and allergies in offspring.
195
Intriguing, but not yet at all reliable, evidence hints that fish oil, or its constituents, might be helpful for treating
kidney stones
or alleviating the symptoms of
chronic fatigue syndrome
, and reducing the risk of prostate
cancer
.
54,56,58,59
Results are inconsistent regarding whether the use of fish oil can decrease seizure frequency in people with
epilepsy
.
209,246
One study found that insulin metabolism in 278 young, overweight subjects improved on a calorie-restricted diet rich in fish oil from seafood or supplements compared to those on a diet low in fish oil, suggesting that fish oil may help delay the onset of
diabetes
in susceptible individuals.
258
Fish oil has also been proposed as a treatment for many other conditions, including
diabetic neuropathy
,
60allergies
, and
gout
, but there has been little real scientific investigation of these uses.
Some, but not all, studies suggest that fish oil combined with
omega-6 essential fatty acids
may augment the effectiveness of calcium in the treatment of
osteoporosis
.
86,87
One promising, but highly preliminary, double-blind,
placebo-controlled
study suggests that the same combination therapy may improve symptoms of the severe neurological illness called Huntington’s disease.
155
Use of a fish oil product as part of a total parenteral nutrition regimen (intravenous feeding) may help speed recovery after major
abdominal surgery
.
233
For several other conditions, the current balance of the evidence suggests that fish oil is
not
effective.
For example, despite widely publicized claims that fish oil helps
asthma
, most preliminary studies have failed to provide evidence that it is effective, and one study found that fish oil can actually worsen aspirin-related asthma.
69-77,171,271
However, there is some evidence that use of fish oil could help prevent exercise-induced asthma in athletes.
196,212
And, in an interesting randomized, controlled trial with long-term follow-up, mothers who take fish-oil during late pregnancy reduced the risk of asthma in their children up to 16 years later.
263
At least two studies, including a systematic review of 4 trials, have not found evidence to support the use of fish oil for improving lung function in people with cystic fibrosis.
251,281
A 16-week, double-blind, placebo-controlled study of 167 individuals with recurrent
migraine headaches
found that fish oil did not significantly reduce headache frequency or severity.
149
Conflicting results have been seen in other, much smaller trials of fish oil for migraines.
172,173
One study found weak evidence that use of fish oil might decrease aggressive behavior in young girls (but, in this study, not in young boys).
213
Another study found benefit in developmental coordination disorder (a condition in which children suffer from lack of physical coordination as well as problems with learning and behavior).
214
Fish oil is also sometimes recommended for enhancing immunity in
HIV
infection. However, one 6-month, double-blind study found that a combination of the omega-3 fatty acids in fish oil plus the amino acid arginine was no more effective than
placebo
in improving immune function in people with HIV.
78
Fish oil, however, might help individuals with HIV gain weight.
79
In one large, randomized, controlled trial, diets rich in fish and omega-3 fatty acids from fish were associated with a significant reduction in the risk of developing colorectal cancer among men over a 22-year period.
255
Another study provides preliminary evidence for the benefits of fish oil in reducing the risk of prostate cancer.
57
On balance, however, there is still relatively little evidence that the consumption of fish oil
reduces cancer risk
.
215
Preliminary studies have suggested that fish oil could help symptoms of
multiple sclerosis
; however, the largest double-blind study on the subject found no difference between people taking fish oil and those taking olive oil (used as a placebo).
80-84,216
Although one study found fish oil somewhat helpful in
psoriasis
,
133
a much larger study found no benefit.
134
DHA has been evaluated as a possible treatment for
male infertility
, but a double-blind trial of 28 men with impaired sperm activity found no benefit.
85
Combination therapy with GLA and fish oil has failed to prove effective for
cyclic breast pain
.
186
One study failed to find fish oil more effective than placebo for treating
stress
.
217
DHA has also been tried for slowing the progression of
retinitis pigmentosa
(a condition in which the retina gradually degenerates), but without much success.
210-211
In observational studies, people who happen to consume a diet rich in omega-3 fatty acids seem to lower their risk of
age-related macular degeneration
(the most common cause of blindness in the elderly). However, in the absence of randomized controlled trials, it is not possible to say whether or not it is omega-3 that produces this benefit.
260
Studies of fish oil have failed to find it helpful for
Alzheimer's disease
, whether for slowing its progression or improving symptoms.
230,240
In addition, two randomized trials have failed to find any benefit of fish oil for
enhancing memory and mental function
in older adults without dementia.
265,280
Use of essential fatty acids in the omega-3 family has also shown some promise for the treatment of non-alcoholic fatty liver.
245,270
A 12-week, double-blind, placebo-controlled trial involving 68 healthy medical students without anxiety disorders found that taking fish oil supplements may reduce
anxiety
(ie, stress related to test taking).
282
What Is the Scientific Evidence for Fish Oil?
Heart Disease Prevention
Studies on fish or fish oil for preventing cardiovascular disease, slowing the progression of
cardiovascular disease
, and preventing heart-related death have returned somewhat contradictory results.
106-125,150,156
A major review published in 2004 failed to find trustworthy evidence of benefit,
218
and a subsequent study actually found that use of fish oil
increases
risk of sudden death in people with stable heart disease.
219
A 2008 systematic review found that fish oil was associated with modestly reduced cardiac mortality, but not sudden cardiac death, in 11 studies totally over 32,000 patients. The reliability of these results, however, is limited by the inclusion of mostly low-to-moderate quality trials.
272
A 2009 review pooled data from 8 trials examining the effect of omega-3 fatty acids on prevention of cardiac death in almost 21,000 patients with coronary heart disease.
274
This review separated patients into two general groups (those with previous myocardial infarction versus those with angina history) and found that omega-3 supplementation reduced risk of sudden cardiac death in patients with previous myocardial infarction, but
increased
risk in patients with angina. Though compelling, this finding may be limited since it was derived from a retrospective analysis of original data reorganized into subgroups.
Finally, a 2012 review of 14 randomized, controlled trials involving over 20,000 people further questions the supplement's value in patients with cardiovascular disease.286 Researchers concluded that omega-3 fatty acids (ranging from 0.4-4.8 g/day) were no better than placebo at reducing rates of cardiovascular events or cardiovascular-related death.
A gigantic study (over 18,000 participants) published in 2007 was widely described in the media as finally proving beyond a shadow of a doubt that fish oil helps prevent heart problems.
239
Unfortunately, this study lacked a placebo group, and therefore failed to provide reliable evidence.
As noted earlier, fish oil is hypothesized to exert several separate effects that act together to help protect the heart. The most important action of fish oil may be its apparent ability to reduce
high triglyceride levels
. Like cholesterol, triglycerides are a type of fat in the blood that tends to damage the arteries, leading to heart disease. According to most, though not all studies, fish oil supplements can reduce triglycerides by as much as 25%-30%.
90-93,151,256
In a detailed review of 47 randomized trials, researchers concluded that fish oil is capable of significantly reducing triglyceride levels with no change in total cholesterol levels and only slight increases in HDL (“good”) cholesterol and LDL (“bad”) cholesterol.
268
However, in some studies, use of fish oil has markedly raised LDL cholesterol, which might offset some of the benefit.
A 2009 review of 30 trials involving about 1,500 patients with type 2 diabetes demonstrated that marine-derived omega-3 polyunsaturated fatty acids (mean dose 2.4 g per day) lowered triglyceride levels about 15 mg/dL but increased LDL cholesterol by about 3 mg/dL after an average 24 weeks of treatment.275
Fish oil has been specifically studied for reducing triglyceride levels in people with
diabetes (a major risk factor for cardiovascular disease), and it appears to do so safely and effectively.
3,262
In one large trial, however, Omacor (the specially-processed, FDA-approved omega-3 product) was not found to benefit people with diabetes or prediabetes.287 Over 12,000 such patients were randomized to receive Omacor (1 g) or placebo. All of the study participants had cardiovascular disease or had risk factors for the disease. Six years later at the follow-up, researchers found that there were no differences between the two groups in regards to cardiovascular-related death, heart attacks, strokes, or heart-related hospitalizations and surgeries. The only bright spot was that Omacor did help to reduce high triglyceride levels.
Stanols
and sterols (or phytosterols) are naturally occurring substances found in various plants that can help to lower cholesterol in individuals with normal or mildly to moderately elevated levels. A study investigating the possible benefit of combining a phytosterol with fish oil found that together they significantly lowered total cholesterol, LDL-cholesterol and triglycerides, and raised HDL (“good”) cholesterol in subjects with undesirable cholesterol profiles.
257
It also seems to remain effective in individuals who are already using statin drugs to control lipid levels (both people with and without diabetes).
14,15,197
However, one study found that the standard drug
gemfibrozil
is more effective than fish oil for reducing triglycerides.
94
Some but not all studies suggest that fish, fish oil, or EPA or DHA separately may additionally raise the level of HDL ("good") cholesterol and possibly improve other aspects of cholesterol profile as well.
96,97,151,164,165,197
This too should help prevent heart disease.
Additionally, fish oil may help the heart by "thinning" the blood and by reducing blood levels of
homocysteine
,
98,176,190
although not all studies have found a positive effect.
198
Studies contradict one another on whether fish oil can lower
blood pressure
,
99-104,177,264
but on balance the supplement does seem to exert a modest positive effect.
174
A 6-week, double-blind, placebo-controlled study of 59 overweight men suggests that the DHA in fish oil, but not the EPA, is responsible for this benefit.
105
A large Italian trial involving almost 7,000 subjects found that fish oilmay modestly reduce the risk of death or admission to the hospital for cardiovascular reasons in patients suffering from
congestive heart failure
.
266
And, a smaller study involving 138 patients showed similarly beneficial results.
279
Evidence is conflicting on whether fish oil helps prevent
arrhythmias
.
220-224,248,285
In a 2010 study involving 663 people with intermittent atrial fibrillation (the most common cause of arrhythmia), fish oil was no more effective than placebo at reducing the number symptomatic episodes over a 24-week period.
278
Fish oil may slightly reduce heart
rate
.
225
This effect could contribute to preventing heart attacks and other heart problems.
Rheumatoid Arthritis
The results of numerous small double-blind trials indicate that omega-3 fatty acids in fish oil can help reduce the symptoms of
rheumatoid arthritis
.
126,127,179,187
At least one small study suggests that it may help rheumatoid arthritis patients lower their dose of nonsteroidal anti-inflammatory medication (eg, ibuprofen).
253
The benefits of the fish oil effect may be enhanced by a vegetarian diet.
187
Simultaneous supplementation with olive oil (about two teaspoons daily) may further increase the benefits.
226
However, unlike some conventional treatments, fish oil probably does not slow the progression of rheumatoid arthritis.
Menstrual Pain
Regular use of fish oil may reduce the pain of
menstrual cramps
.
In a 4-month study of 42 young women aged 15 to 18, half the participants received a daily dose of 6 g of fish oil, providing 1,080 mg of EPA and 720 mg of DHA daily.
128
After 2 months, they were switched to placebo for another 2 months. The other group received the same treatments in reverse order. The results showed that these young women experienced significantly less menstrual pain while they were taking fish oil.
Another double-blind study followed 78 women, who received either fish oil, seal oil, fish oil with vitamin B
12
(7.5 mcg daily), or placebo for three full menstrual periods.
129
Significant improvements were seen in all treatment groups, but the fish oil plus vitamin B
12
proved most effective, and its benefits continued for the longest time after treatment was stopped (3 months). The researchers offered no explanation why vitamin B
12
should be helpful.
Bipolar Disorder
A 4-month, double-blind, placebo-controlled study of 30 individuals suggests that fish oil can enhance the effects of standard treatments for
bipolar disorder
, reducing risk of relapse and improving emotional state.
130
Eleven of the 14 individuals who took fish oil improved or remained well during the course of the study, while only 6 out of the 16 given placebo responded similarly.
In addition, a systematic review of 6 randomized trials involving 320 people found that those who took omega-3 fatty acids had an improvement in their bipolar depression symptoms.
284
A small study also found that ethyl-EPA (a modified form of EPA) is helpful for the depressive phase of bipolar disease.
227
Depression
A 4-week, double-blind, placebo-controlled trial evaluated the potential benefits of fish oil in 20 individuals with
depression
.
154
All but one participant were also taking standard antidepressants and had been taking them for at least 3 months. By week 3, the level of depression had improved to a significantly greater extent in the fish oil group than in placebo group. Six of 10 participants given fish oil, but only one of 10 given placebo, showed at least a 50% reduction in depression scores by the end of the trial. (A reduction of this magnitude is considered a “cure.”)
A double-blind, placebo-controlled study of 70 people who were still depressed despite standard therapy (such as
SSRIs
) found that additional treatment with ethyl-EPA (a modified form of EPA) improved symptoms.
175
Similar add-on benefits were also seen in other double-blind studies of ethyl-EPA or mixed essential fatty acids.
192-193,228,250
However, one study failed to find benefit with fish-oil as an add-on treatment.
229
Another double-blind study failed to find DHA alone helpful for depression.
188
A third relatively large placebo-controlled study found no benefit for fish oil in improving “mental well-being” among 320 older adults without a diagnosis of depression.
267
Postpartum Depression
The effectiveness of fish oil supplementation in treating or preventing perinatal (including postpartum) depression is, as of yet, unclear.
A small preliminary study of women found that fish oil was significantly more effective than placebo at alleviating postpartum depression.
252
However, another small, placebo-controlled study was unable to show a benefit in women suffering from depression whether before or after delivery.
249
In addition, a 2009 trial of 182 pregnant women with suspected low intake of DHA found that daily DHA supplementation (with or without arachidonic acid) did not reduce risk of postpartum depression compared to placebo.
273
And, inanother much larger study involving 2,399 women, researchers found that fish oil capsules (a combination of DHA 800 mg/day and EPA 100 mg/day) did not prevent postpartum depression. Interesting, it also did not improve the cognitive and language development in their children up to four years after their birth.
277
Raynaud's Phenomenon
In small, double-blind studies, fish oil has been found to reduce the severe finger and toe responses to cold temperatures that occur in
Raynaud's phenomenon
.
131,132
However, these studies suggest that a higher than usual dosage must be used to get results, perhaps 12 g daily.
Osteoporosis
There is some evidence that essential fatty acids may enhance the effectiveness of calcium in
osteoporosis
. In one study, 65 postmenopausal women were given calcium along with either placebo or a combination of omega-6 fatty acids (from evening primrose oil) and omega-3 fatty acids (from fish oil) for a period of 18 months. At the end of the study period, the group receiving essential fatty acids had higher bone density and fewer fractures than the placebo group.
135
However, a 12-month, double-blind trial of 42 postmenopausal women found no benefit.
136
The explanation for the discrepancy may lie in the differences between the women studied. The first study involved women living in nursing homes, while the second studied healthier women living on their own. The latter group of women may have been better nourished and already received enough essential fatty acids in their diet.
Lupus
Lupus
is a serious autoimmune disease that can cause numerous problems, including fatigue, joint pain, and kidney disease. One small, 34-week, double-blind, placebo-controlled crossover study compared placebo against daily doses of EPA (20 g) from fish oil.
137
A total of 17 individuals completed the trial. Of these, 14 showed improvement when taking EPA, while only 4 did so when treated with placebo. Another small study found similar benefits with fish oil over a 24-week period.
191
However, two small studies failed to find fish oil helpful for lupus nephritis (kidney damage caused by lupus).
138,139
Attention Deficit and Hyperactivity Disorder (ADHD)
Based on evidence that essential fatty acids are necessary for the proper development of brain function in growing children, EFAs have been tried for the treatment of
ADHD
and related conditions. The results has been mixed.
A preliminary double-blind, placebo-controlled trial found some evidence that a supplement containing fish oil and
evening primrose oil
might improve ADHD symptoms.
140
However, a high drop-out rate makes the results of this trial unreliable. In a double-blind, placebo-controlled trial of children already using stimulant therapy, addition of DHA for 4 months failed to further improve symptoms.
141
A systematic review produced slightly more promising results, though. In the review, 10 randomized trials involving 699 children with ADHD found that those who took omega-3 fatty acids experienced a modest improvement in certain symptoms like inattentiveness and hyperactivity.
283
Another small study examined fish oil in children with ADHD who had thirst and skin problems. Benefits were seen with fish oil, but they also occurred with placebo and to about the same extent.
194