Mid-Life Weight Loss’s Hidden Cost To The Brain

For most people in the US, losing weight is generally considered a health-positive thing, unless one is underweight to begin with, of course—but then, “underweight to begin with” is already not “most people in the US”.

However, there can be costs.

When less is not always more

We’ve written before about how a lot of mainstream belief presupposes thinness as desirable, and presumes it to be healthy, which frankly, it’s not for everyone. Indeed, for people over a certain age, having a BMI that’s slightly into the “overweight” category is a protective factor against mortality:

When BMI Doesn’t Quite Measure Up

It now seems that there are also such considerations when it comes to brain health. Generally speaking, have a high body fat percentage will tend to put a strain on the heart, and what’s bad for the heart is bad for the brain, because the latter relies on the former to provide it with a healthy flow of blood bearing oxygen and nutrients, and ultimately take away detritus once the glymphatic system has got it out of the brain itself (having a good glymphatic system and poor circulation is an unlikely combination, but if it somehow occurred, the result would be much like if you empty the trash from your house but there’s no municipal service to come pick it up and take it away).

For more on that, see:

• What’s Your Vascular Dementia Risk? ← for the brain-heart connection in general
• How To Clean Your Brain (Glymphatic Health Primer) ← for what we just talked about
• Take Care Of Your Lymphatic System To Beat Cognitive Decline ← because this too plays a part (an indirect part, but an important one nevertheless)

Fat & neuroinflammation

It is known that metabolic dysfunction (as is strongly associated with fat storage in the liver, visceral fat, and less importantly, subcutaneous fat deposits), is a driver of inflammation in general, which in turn makes the metabolic dysfunction worse.

Poorly regulated or persistent brain inflammation has been linked to memory impairment and neurodegenerative diseases such as Alzheimer’s, which is why research has been done into how midlife weight loss might interact with long-term brain health.

Most recently, a mouse study found: Weight loss aggravates obesity-induced hypothalamic inflammation in mid-aged mice

Now, that’s a mouse study and not too exciting in and of itself, but the underlying science is quite applicable, because as it turns out:

❝Combined overconsumption of fat and sugar, but not the overconsumption of fat per se, leads to excessive CML production in hypothalamic neurons, which, in turn, stimulates hypothalamic inflammatory responses such as microgliosis and eventually leads to neuronal dysfunction in the control of energy metabolism.❞

Read in full: Dietary sugars, not lipids, drive hypothalamic inflammation

Which becomes further relevant when: Diet triggers specific responses of hypothalamic astrocytes in time and region dependent manner

Now, that’s about diet, but what of weight loss itself? What if you don’t change your diet but you lose weight for some other reason (intentionally or otherwise; perhaps you changed your exercise routine, perhaps you got ill, etc)?

The short answer is: stability of weight is generally better than strong fluctuation in either direction

Now, this one’s about men rather than mice, so its applicability to women (most of our readers) is not as strong as if it were about women, but it’s worth bearing in mind in any case. It looked at 1,160 men aged 40–59 years at the start of the experiment, and was then a prospective study, i.e. looking at the next 15 years of follow-up, and found:

❝Results: Overall, 183 deaths were observed among the 505 men. Only weight fluctuations had a clear significant impact on all-cause mortality. Adjusted hazard rate ratio (HRR (95%-CI)) was 1.86 (1.31-2.66) after adjustment for age group, pre-existing cardiovascular disease or diabetes mellitus, smoking and socio-economic status. The risk rate due to weight loss was borderline significant (HRR = 1.81 (0.99-3.31)). Risk of death due to weight gain (HRR = 1.15 (0.70-1.88)) or stable obesity (HRR = 1.16 (0.69-1.94)), however, were not significantly increased compared to men staying non-obese for the first 15 years after cohort recruitment.

Conclusion: Weight fluctuations are a major risk factor for all-cause mortality in middle-aged men. Moreover, stable obesity does not increase further mortality in men aged 55-74 years in long-term follow-up.❞

Read in full: Weight change, weight cycling and mortality in the ERFORT Male Cohort Study

So, in other words, even beyond brain health, and even for all-cause mortality, stable is best.

Want to learn more?

You might like this book that we reviewed a while back:

“You Just Need to Lose Weight” And 19 Other Myths About Fat People – by Aubrey Gordon

Take care!