You might have seen the following headline on “Psychology Today” this week:
“Do Fatty Foods Deplete Serotonin Levels?” (1)
You might have also seen this article shared on Reddit, with a headline reading:
“Fatty foods may deplete serotonin levels, and there may be a relationship between this and depression, suggest a new study, that found an increase in depression-like behavior in mice exposed to the high-fat diets, associated with an accumulation of fatty acids in the hypothalamus.” (2)
At first glance, these statements might make us want to cut the fat from our diets.
But what does the study in question actually tell us?
Do “fatty foods” actually increase our risk for depression?
Or are these more nonsense nutrition headlines?
The study, titled “A high-fat diet promotes depression-like behavior in mice by suppressing hypothalamic PKA signaling” was published May 10, 2019, in Translational Psychiatry (3).
The study authors looked at three groups of mice:
- One group, the control, were wild-type (WT) mice eating a “normal diet” (ND)
- Another group of WT mice eating a “high fat diet” (HFD) with 60% of its calories coming from fat (it’s not clear what percentage of calories came respectively from carbs and protein).
- A third group of genetically leptin-deficient (ob/ob) mice – predisposing them to overeating, weight gain, impaired glucose control, and low metabolic rate – eating the “normal diet”.
Compared to the control, both the HFD mice and the ob/ob mice demonstrated changes in behavior symptomatic of depression.
That brings us to the first question we must ask about how this study’s findings are presented.
If diet was not a common factor in the mice that developed symptoms of depression, why do the study title and the Reddit headline imply that diet is to blame?
Even the authors acknowledge repeatedly that both diet-induced obesity and genetically-induced obesity play a role in the development of symptoms of depression.
From the Introduction:
“In the present study, we found that either dietary or genetically induced obesity (GIO) in mice lead to depression phenotype and this phenomenon occurs via the disruption of the cAMP/PKA signaling pathway.”
From the Results:
“These results suggest that like DIO, GIO promotes the development of a depressive-like phenotype in mice.”
From the Discussion:
“Using behavioral paradigms in mice, we demonstrated, as have others previously, that either DIO or GIO can be causative for the development of depression.”
If there’s something I’m missing, feel free to comment below or send me a message, because I’m baffled as to why the HFD would be presented as the critical factor in the observed outcomes.
The next question we might ask, then, is what, if not diet, is responsible for the symptoms of depression?
Overeating, weight gain, insulin resistance, and the hypothalamus
Fortunately, there are similarities between the HFD mice and the ob/ob mice that we can explore in our search for what caused the change in behavior.
Both the HFD and ob/ob mice ate more than the control group.
Both the HFD and ob/ob mice gained weight.
Both the HFD and ob/ob mice showed changes in gene expression associated with depression in a region of the brain called the hypothalamus.
The HFD mice showed fat accumulation in the hippocampus, which the scientists concluded was responsible for the change in behavior.
The study doesn’t say anything about hypothalamic fat accumulation in the ob/ob mice, but it’s not unreasonable to assume that this was the case considering the similarities in other upstream and downstream effects.
Let’s talk about some of these observations individually before connecting the dots.
Hypothalamic fat accumulation is associated with insulin resistance (4).
While insulin resistance isn’t fully understood and is thought to have several contributing factors, one idea that’s gaining momentum is that it serves as a response to – even a protective mechanism against – excessive energy intake (5, 6).
Thus, it’s plausible that both the HFD mice and the ob/ob mice developed depression driven by the accumulation of fat in the hypothalamus, as a result of insulin resistance driven by weight gain and energy excess.
Dietary fat and the hypothalamus
So, would the mice have seen the same results if they were eating the same HFD but their calories were controlled to prevent weight gain?
There is research indicating that dietary fat can promote fat accumulation in the hypothalamus independent of energy intake (7).
Additionally, the behavior changes do appear to be a bit more pronounced in the HFD mice than the ob/ob mice (see fig. 1 above).
Thus, it’s possible that the HFD mice would have seen similar effects even without the weight gain, driven by the increased fat content of the diet alone.
However, that the ob/ob mice eating the normal diet developed similar outcomes suggests that the excessive energy intake was an important factor in the effects observed in this study.
Does this mean you or I might see a similar higher risk for depression with increased fat intake, independent of energy intake?
One review concludes “saturated fats have been correlated with symptoms of depression in humans. In contrast, dietary monounsaturated fats tend to be inversely associated with symptoms of depression in humans. Similarly, dietary n-3 fats are most often associated with improvements in depression, although there is some inconsistency in the literature. Finally, positive associations between n-6 fats and risk of suffering from severe depression in humans have been reported.” (8)
Another study showed a relationship between trans fatty acid intake and depression, but a negative correlation between monounsaturated fatty acid intake an polyunsaturated fatty acid intake, with no association observed “for n-3, n-6, n-3 from fish or the ratio between n-3 vs n-6 fatty acids intake” (9).
It appears fat quality (if not quantity) does play an important role in risk of depression, with monounsaturated fats and omega-3 polyunsaturated fats being the safest bet.
Dietary fat and overeating
In case you’re thinking that you still might avoid a high fat diet due to the potential drive to eat more, let’s shift gears for a second and talk about “high fat” diets and overeating – particularly with mice.
One study from 2018 showed that a diet with 60% of calories from fat appears to be the “sweet spot” for driving mice to eat more and gain weight (10).
In that study, as fat content of the diet increased to 60% of total calories, the mice ate less food by mass but the reduction of food was not sufficient to account for the increased energy density of the food.
Once fat content of the diet increased above 60%, however, the mice ate sufficiently less to account for the increased energy density and their total caloric intake dropped as fat content increased.
If you’d like to read more about this study, I wrote about it here.
The main take away is that it may not necessarily be that fat inherently drives consumption and, thus, weight gain.
Rather, that eating just the right amount of fat – 60% of total calories – drives consumption and promotes weight gain.
Foods combining fat and carbohydrate – specifically sugar – have been shown to be “hyperpalatable” and promote overeating (11).
Consider that most comfort and dessert foods we eat aren’t simply high carb or high fat, but high in both.
We might think of these mice eating diets of 60% fat as being given snacks and treats all day.
While the relationship between obesity and depression is complex, this meta-analysis does show that depressed compared to non-depressed people were at significantly higher risk of developing obesity (12).
Thus, it’s not unreasonable that we’d see similar weight gain, insulin resistance, hypothalamic lipid accumulation, and depression in humans driven by hyperpalatability to overeat and gain weight.
There’s at least the possibility that, even if one isn’t directly driving the other, both the depression and the obesity could result from common problematic eating habits, including overeating driven by hyperpalatability.
What you can do
While the role of nutrition in mental health involves far more than the effects of fat on the hypothalamus, here are a couple of steps you might take to minimize risk of what was seen in this study:
1) Avoid energy excess.
I know that this is easier said than done, but it’s worth pointing out.
The common factor in mice in this study that developed symptoms of depression was overeating.
Taking steps to match your energy intake with your energy needs doesn’t require cutting out fats or carbs.
The DIETFITS study (one of my favorites) demonstrated that we can improve our body composition and our health by reducing either carbohydrates or fat intake, so long as there’s an emphasis on finding a sustainable approach based around minimally processed, nutrient-dense foods (14).
Steering clear of hyper-palatable foods combining salt, sugar, fat, and different textures will likely serve you well in terms of managing energy intake.
2) Emphasize quality fats.
Recall that trans fats, but not monounsaturated fats or polyunsaturated fats, were associated with depression.
To avoid trans fats, steer clear of packaged foods and partially hydrogenated oils (check labels).
Prioritize monounsaturated fats like olives, olive oil, avocado, and almonds.
Seek out polyunsaturated fats from nuts, seeds, and fatty cold-water fish like salmon and mackerel.
Pay attention also to lifestyle factors other than nutrition that play a role in your risk for depression.
Sleep, stress management, nature, relationships, and living a life of purpose are all factors you’ll want to consider for optimal mental, physical, and emotional health.
Finally, if you suspect that you might benefit from the help of a professional, don’t hesitate to seek out counseling, therapy, or other treatment.
Mental health is a serious subject and you deserve nothing but to feel awesome.
If you need a little help towards that end, get it.
Remember to take nutrition headlines with a grain of salt.
Focus on the basics.
Aim for consistency, rather than perfection.
Do it for no other reasons than that you freaking rock.
You are worthy.
You’ve got this.