From Podcast, ,

Omega-3 fatty acids do treat depression, but not with the formulations that are commonly found on the shelves. Here we point you in the right direction, and give a winding origin story of these essential fatty acids.

CME: Podcast CME Post-Tests are available using this subscription. If you have already enrolled in that program, please log in.

Published On: 03/07/2022

Duration: 22 minutes, 21 seconds

Chris Aiken, MD, and Kellie Newsome, PMHNP, have disclosed no relevant financial or other interests in any commercial companies pertaining to this educational activity.

Transcript:

Omega-3 fatty acids do treat depression, but not with the formulations that are commonly found on the shelves. Today, we’ll point you in the right direction.

Welcome to the Carlat Psychiatry Podcast, keeping psychiatry honest since 2003. I’m Chris Aiken, the editor in chief of the Carlat Report. And I’m Kellie Newsome, a psychiatric NP and a dedicated reader of every issue.

CHRIS AIKEN: Every branch of medicine has a guiding idea about how they cure disease. Internists medicate it. Surgeons cut it out. And psychiatrists are a varied bunch. Not long ago we saw ourselves as the instrument in the cure, as psychotherapists, negotiating a truce between the ego and the id, or challenging the unchecked powers of automatic negative thoughts. But today, we mostly medicate.

But a third path is being paved by a loosely knit group of researchers who are linking psychiatric illness to changes in our environment, diet, sleep patterns, and social life. It’s an old story – one that beckons back to Hippocrates – but one that’s being retooled for modern times as many changes in how we live can contribute to psychiatric illness. We sit around all day, work too much, socialize too little, and fall asleep under the blue light of the screen. And we don’t eat like we used to. While our ancestors ate a seafood rich diet as they built civilizations along the rivers and seas; we eat frozen and processed foods and build our cities along the interstate exits that transport them. And a few things can go wrong when seafood is no longer a staple of the diet.  

For example, there’s the essential fatty acids, which are called essential because you can’t make them on your own – you need to get them from what you eat. Today we’re going to focus on an essential fatty acid that plays an outsized role in the brain – omega-3 fatty acids, or fish oil. But first, a preview of the CME quiz for this podcast.

Which medication can cause side effects that improve with omega 3?

A. Lithium

B. SSRI Antidepressants

C. Valproic acid

D. Modafinil

KELLIE NEWSOME: Fish is the main dietary source of omega-3’s, but particularly oily fish like salmon, mackerel, tuna, herring, sardines, as well as mussels, oysters, and caviar. You’d need to eat 1-2 servings of oily fish a week to get an adequate dose, while for other fish you’d need to indulge in 1 serve a day. Non-fishy sources include nuts – especially walnuts; seeds like flax; beans like Edamame and fruits like berries and kiwi. 

What these omega-3s do is coat brain cells, building the flexible phospholipid membrane that protects the cell and helps it communicate with other neurons. They do that through a unique chemical property – their top hydrophobic half repels water away, sealing the cell so it doesn’t flood and burst, but their bottom half – the part that points into the nerve cell – is hydrophilic – water loving, allowing the inside of the cell to maintain a healthy, homeostatic water balance. 

That’s the biochemistry, but here’s how I describe it to patients. The brain is like a piece of fine leather. You need to oil it, or it turns brittle, just like a leather car seat that’s dried up in the sun without any oil on it. And the oil the brain needs is fish oil. Most of us don’t get enough from our diet unless we’re eating at least one serving of an oily fish like salmon each week, or a daily serving for most other fish. When the brain doesn’t get enough, it substitutes cheaper ingredients like cholesterol, which makes the brain cells more inflexible and less able to adapt to stress. And that’s kind of what it’s like when you’re depressed or irritable – your mind is inflexible, stuck in negative or angry thoughts, and you have trouble finding creative, flexible solutions to life’s problems.

CHRIS AIKEN: Your analogy reminds me of a study where they looked at what happens to the brain after taking omega-3’s, using T2 relaxation times on an MRI in patients with bipolar disorder comparing those who received omega 3 to those who did not. On omega 3, the brain cells were more fluid – exactly what you’d predict

KELLIE NEWSOME: And we see it in the skin as well, which of course is what leather is made from. Supplementation with omega-3’s improves dermatitis, skin ulcers, and protects the skin against 3 dermatologic side effects that we sometimes encounter with mood stabilizers. 

1. Photosensitivity with lamotrigine, as well as with tricyclics and antipsychotics. If you live in a sunny climate, your patients are more likely to sunburn on these meds, so warn them to wear sunscreen with an SPF of at least 30. Omega-3’s give the skin another layer of protection against ultraviolet damage.
2. Acne and psoriasis on lithium. 10 controlled trials have found that omega 3’s improve psoriasis, and a few found benefits in acne.  

CHRIS AIKEN: Omega 3’s are low-risk, and improve many health problems that our patients suffer from. They are FDA cleared for high triglycerides, and have evidence to help hypertension, inflammatory bowel disease, dry eyes, macular degeneration, fatty liver, arthritis, and asthma. But for most of these medical disorders – including psoriasis and acne – they use doses that are about double what we use in psychiatry.  And if you decide to use omega-3’s for mental health, dosing is everything, and it’s a little complex. This month, we feature an up-to-date review of omega 3’s in psychiatry. We concluded they have a small to medium effect in depression, bipolar depression, ADHD, borderline personality disorder, negative symptoms of schizophrenia, and non-specific irritability. How much is a small to medium effect? It’s not so bad – more than buspirone but little less than an antidepressant. 

But wait – maybe your patients are already taking them and you’re not seeing much difference! Well, listen up. There are two types of omega-3’s: EPA and DHA, and we noticed a distinct pattern around the ratio of these two as we combed through over 40 randomized controlled trials. Omega-3’s did not work so well when the trials used products with a lot of DHA, but they had a decent effect when the product was rich in EPA. In our online article we give you the exact specs on the optimal EPA:DHA ratio, the total daily dose, and list 10 low-cost, lab-tested products that have the correct amounts. 9 of them are over the counter, and 1 is prescription only. 

They weren’t easy to track down, because most products on the market are high in DHA, probably because food sources of omega-3’s have more DHA. So most of your patients have probably been taking the wrong omega-3. When I learned about this distinction a few years ago I started to see better results in my practice. I remember one patient who flew to Europe and forgot to take his high EPA fish oil along with him – within a few days he got depressed on what would have been an otherwise joyful holiday.

KELLIE NEWSOME: You ever wonder how we got the idea to use omega-3’s in psychiatry? We’ll end this podcast with that origin story, and like all origin stories, it’s kind of arbitrary where it begins, because everything is connected in this human web, so let’s start with a holiday we recently past by: Valentine’s day, 2022, and journey to the romantic city of Rome, behind the Vatican walls, where a building houses one of the oldest orders of the Catholic Church, the Congregation for the Doctrine of the Faith.

CHRIS AIKEN: The Congregation for the Doctrine of the Faith is the arm of the Vatican that keeps doctrinal order in the Church, and on February 14, 2022 Pope Frances issued a decree to overhaul this ancient body. To quote the Pope, he wants the Congregation to respond to “questions posed by the progress of the sciences and the development of society.” Gay marriage is high on the list of those societal questions. The Pope also wants to shore up the disciplinary arm of the Congregation. They’ve focused on weeding out heresy for centuries, but the rise of clerical sexual abuse has overwhelmed their dockets, which currently have a backlog of 4,500 disciplinary cases to review.

This high court can cause clergy to lose their jobs or force them to recant their radical ideas, but not long ago the punishments were more severe. The wages of heresy were death, and the last heretic to be executed by the Congregation was Cayetano Ripoll, a school teacher who was hanged in 1826 for teaching his students to discern the truth through empirical observation rather than divine inspiration. The governing body responsible for Ripoll’s death is the same one that Pope Frances is trying to reform. Back then, it was known as the inquisition, or its official title: The Congregation of the Holy Roman and Universal Inquisition. The church changed the name in 1908 to distance it from the tarnished reputation of the Inquisition that it started from, but the institution is the same one that put heretics to death for centuries until the harsher edge of the movement was reined in by the French Revolution and the Napoleonic wars. 

Among all the inquisitions, the Spanish were the most brutal, and it was this inquisition that spread fish oil throughout Europe.

KELLIE NEWSOME: In 1478, Spain launched an inquisition to expel, kill, or force the conversion of Jews and Muslims. To escape this persecution, many Sephardic Jews to took refuge in England, and when they did they brought with them a culinary tradition that the British would soon embrace: Fish and Chips. The Sabbath forbids work on Saturdays, including cooking, so the Portuguese Jews developed a way of frying fish that they could eat as left-overs on Saturday. They introduced this to England, and when Thomas Jefferson visited England he wrote admiringly of “fried fish in the Jewish fashion.” As industrial fishing spread in the 1800’s, Fish and chips became a staple in England, and so did a byproduct of the greasy meal: cod liver oil.

Unlike humans – who store fat in their waist, skin, buttocks and breasts – codfish store fat in their liver, and up to half a cod’s weight is in the liver alone. Physicians dating back to Hippocrates have written of the healing benefits of the cod liver, so the fishing industry started extracting this omega-3 rich oil and selling it as a healthy elixir. 

Soon physicians were prescribing cod liver oil for all kinds of ailments, especially to prevent rickets and treat arthritis. The oil is 20% omega-3’s, but it also has vitamins A and D, and physicians thought it was these two vitamins that were responsible for its healing properties. That didn’t add up, however, as giving those vitamins on their own didn’t produce the same effects as the full oil. There was something else in the oil, and in 1979 a remarkable research study gave a hint of what it was. To understand that, we have to travel back a thousand years to Greenland, the year 980. Not 1980, 980.

CHRIS AIKEN: Long before Columbus “discovered” the new world, Nordic explorers from Iceland led by Erik the Red landed on the southwest coast of Greenland in 980. They lived there alongside the Inuit Eskimos for nearly 500 years, even briefly landing in Canada under Leif Erikson, until their small colony collapsed in the early 1400’s, shortly before Columbus set sail. No one knows for sure why their civilization collapsed, but they were in constant conflict with the Inuits, and may have suffered famine because they relied on agriculture in this ice-capped climate and never learned the art of kayak fishing from their Inuit neighbors. 

These scant facts lead bio-historian Jared Diamond to speculate that the Nordic settlement collapsed because of Christian prudery in his book Guns, Germs, and Steel. The Europeans simply wouldn’t eat the the nutritious diet of seal and whale that sustained their Inuit neighbors. Diamond’s hypothesis doesn’t tell the whole story, but it does hold a ring of truth, and 500 years after the collapse of that settlement a different kind of Nordic explorers returned to figure out what they were missing in that Inuit diet.

These modern day explorers were of the scientific ilk, and they were drawn to Greenland by a medical mystery. Heart disease is practically unknown among the Inuit Eskimos, which we might expect if they were vegetarians, but the Inuits sustain themselves on a high-fat diet, full of whale and seal. So in the 1970’s Danish physician Jørn Dyerberg flew to Greenland to figure out the Inuit secret. He published his findings in 1979 in the Lancet, and it changed how we think about omega-3 fatty acids. 

KELLIE NEWSOME: Dyerberg’s study was prominently featured in the Lancet, and it had that irresistible combination of medical mystery, novel findings, and Eskimos that gets people talking. Eventually it led to an FDA indication for omega 3’s for lowering triglycerides in 2004. Meanwhile, researchers were figuring out that omega-3’s were also essential to the brain. When rats were raised without omega 3’s in their diet, their brains were profoundly impaired, and their nerve cells demyelinated. That animal research started to translate to human studies in 1977, psychiatrists found that depressed patients had low levels of omega 3, and follow-up studies found the omega-3 level was correlated with the severity of the depression. 

And then in 1998 Joseph Hibbeln, a psychiatrist at the NIMH, keyed in two sets of data on his computer 1) the rates of depression in 9 different countries from a large international study and 2) the rate of fish consumption for each country. When he connected the dots, it formed a straight line – the more fish the country ate, the lower the rate of depression. Japan took first place for good moods and plentiful fish, while New Zealand, Canada, and Germany lagged behind in the rear.

CHRIS AIKEN: A year later, Andrew Stoll and colleagues published the first clinical trial of omega-3 in psychiatry. Working at Harvard Medical School, they recruited 30 patients with bipolar disorder and randomized them to receive either a high dose of omega (9 grams a day) or an olive oil placebo. Early omega-3 trials used olive oil as a placebo, but they’ve since given that up as we know now that extra virgin olive oil has antidepressant effects of its own. But despite this active placebo, the patients in Stoll’s study who took omega 3 stayed well longer. 

Dr. Stoll’s work inspired nearly a hundred trials of omega 3 in psychiatric disorders and everyone from stressed out college students to irritable old men. Now you can’t go into a grocery store without finding omega 3 in the milk, eggs, and peanut butter. We’ve come full circle from the time a century ago when cod liver oil was on every grocery shelf and mother’s gave it to their children in hopes of good health. But is it really the same? We found one study that looked at that question, and it brings us back to Norway, where in 2007 a group of researchers compared rates of depression among 21,000 people based on whether they regularly consumed cod liver oil or not. Those who did had a 30% lower risk of depression.

And now for the word of the day…. Sleep drive

KELLIE NEWSOME: Human and animal models point to two processes that regulate sleep. The circadian rhythm, which is regulated by melatonin and the cycle of light and darkness, and sleep drive, which is simply the force that makes you fall asleep. While circadian rhythm is cyclical, sleep drive is linear: The longer you are awake, the higher it gets. The biology of this drive is not fully understood, but it does involve adenosine, a by-product of cellular energy consumption. Adenosine accumulates throughout the day as you move your muscles and process your thoughts, and eventually reaches a level that zonks you out. That is, unless you’re taking a lot of caffeine, which suppresses adenosine, or watching TV in bed, which will make your circadian drive counteract your sleep drive. And that’s just the start of the mess that people can get into when they have insomnia. Join us next week where we’ll present the top tips from CBT-insomnia that you can bring to your patients.

CHRIS AIKEN: Start earning CME credits for this podcast by following the link in the show notes. Each episode has 2-3 questions. Add them up and you’ll quickly reach a licensable quota.