GLP-1 receptor agonists, energy availability, and the predictable consequences of an under-fuelled brain

There is growing attention on the psychological and neurocognitive effects of GLP-1 receptor agonists. Much of the discussion asks whether these medications themselves cause mental health harm.

That question, however, starts in the wrong place.

The more useful question is not whether GLP-1s are “good” or “bad”, but whether we are adequately accounting for what happens to the human brain when energy availability falls below physiological need, regardless of how that reduction occurs.

This is not new science. It is old, well-established physiology that we repeatedly forget, mislabel, or psychologise.

And when we do, people get harmed.

The brain does not negotiate with an energy deficit

Across eating disorders, semi-starvation, famine exposure, Relative Energy Deficiency in Sport (RED-S), and chronic illness associated with reduced intake, the same pattern appears again and again.

When energy availability drops below requirements, the brain adapts.

Glucose availability to the brain falls. Insulin, leptin, IGF-1 and thyroid signalling are suppressed. Cortisol rises. Neurotransmission and neuroplasticity shift into conservation mode.

The outward presentation is familiar: slowed thinking, narrowed focus, rigidity, obsessionality, heightened anxiety, emotional lability, impaired judgement, reduced insight.

These are not personality traits. They are not moral failures. They are not evidence of intent.

They are predictable adaptations of a brain trying to survive with insufficient fuel.

Crucially, the brain does not distinguish why intake is reduced. It does not care about motivation, compliance, dieting culture, or diagnosis. It responds to energy availability alone.

Why GLP-1s matter in this context

GLP-1 receptor agonists reduce oral intake by design. Appetite suppression, early satiety, delayed gastric emptying, nausea, and reduced food reward are not side effects; they are the mechanism.

If intake falls and is not actively monitored and compensated for, low energy availability follows. Body size does not protect against this. BMI does not buffer the brain.

From decades of starvation and energy-deficiency research, the pattern is consistent:

A sustained energy deficit of ~20–30% is associated with fatigue, reduced concentration, sleep disturbance, irritability, and rising anxiety.

Larger deficits in the range of ~30–40% are associated with more pronounced cognitive rigidity, obsessionality, impaired judgement, and threat sensitivity, often emerging within weeks.

More abrupt or severe deficits, particularly above ~40–50%, are associated with rapid and clinically significant neurocognitive impairment, especially when intake drops suddenly.

These effects are driven by energy availability relative to need, not weight status.

What the newer GLP-1 nutrition data shows

Recent evidence now confirms what physiology would already predict.

A 2026 narrative review by Urbina and colleagues synthesised data from six adult studies encompassing over 480,000 GLP-1 receptor agonist users and identified clinically meaningful nutritional inadequacy during GLP-1 therapy.

Vitamin D deficiency was the most common abnormality, affecting 7.5% of users at 6 months and 13.6% at 12 months. Iron depletion was frequent, with GLP-1 users demonstrating 26–30% lower ferritin levels compared with SGLT2 inhibitor comparators. More than 60% of users consumed below estimated requirements for calcium and iron, while vitamin D intake averaged only ~20% of recommended levels.

Protein insufficiency was common and associated with lean mass loss and sarcopenia risk. Thiamine and vitamin B12 deficiencies increased over time, and multiple case reports of GLP-1–associated Wernicke encephalopathy were identified, nearly all occurring in the context of rapid weight loss, persistent vomiting, or marked caloric restriction.

Perhaps most tellingly, over 90% of patients had no dietitian involvement prior to GLP-1 initiation.

These findings are observational. They do not prove causality.They do not need to.

They align precisely with what we already know happens when the brain is under-fuelled.

Where we keep getting this wrong

When people on GLP-1s develop anxiety, rigidity, low mood, food avoidance, or cognitive fog, these changes are frequently interpreted as psychological, behavioural, or motivational.

They are not.

They are downstream adaptations to energy deficit.

This distinction matters.

When we misattribute starvation physiology as psychology, we respond with therapy, insight, reassurance, or behavioural advice, while leaving the primary driver untouched.

This is the same mistake repeatedly made in eating-disorder care, in RED-S, and in chronic illness. GLP-1s have simply created a new pathway into the same biological state.

Why dietetic oversight is not optional

GLP-1s are prescribed specifically to suppress intake, yet nutritional assessment is often minimal or absent. Energy requirements are rarely calculated. Carbohydrate adequacy is rarely considered in relation to brain function. Protein sufficiency, micronutrient status, and early cognitive warning signs are inconsistently monitored.

Dietitians are trained to assess energy availability. Not weight loss. Not compliance. Energy availability.

Without this lens, under-nutrition is identified late, once cognition and behaviour have already shifted, and is then mislabelled as a mental health issue rather than recognised as a physiological consequence.

From a systems and governance perspective, this is not an unforeseen risk. It is a foreseeable one.

This is not an argument against GLP-1s

Nothing here argues against GLP-1 receptor agonists as therapeutic tools.

It argues against ignoring what low energy availability does to the brain.

It argues against repeating the same misattribution errors under a different clinical banner.

And it argues for treating adequate nourishment as foundational to cognitive and emotional function, not as an optional add-on once problems appear.

Where this fits

This piece sits squarely within the framework explored in Food Mad.

Food Mad is not about blaming behaviour. It is about correcting causality.

When the brain is under-fuelled, behaviour changes.When fuel is restored, cognition changes. The order matters.

Re-centring brain energy needs is not radical.

It is simply a matter of remembering how human physiology works.

References

Keys, A., Brožek, J., Henschel, A., Mickelsen, O., & Taylor, H. L. (1950). The Biology of Human Starvation. University of Minnesota Press.

Loucks, A. B., & Thuma, J. R. (2003). Luteinizing hormone pulsatility is disrupted at a threshold of energy availability in regularly menstruating women. Journal of Clinical Endocrinology & Metabolism, 88(1), 297–311. https://doi.org/10.1210/jc.2002-020369

Mountjoy, M., Sundgot-Borgen, J., Burke, L., et al. (2018). IOC consensus statement on Relative Energy Deficiency in Sport (RED-S): 2018 update. British Journal of Sports Medicine, 52(11), 687–697. https://doi.org/10.1136/bjsports-2018-099193

Kaye, W. H., Fudge, J. L., & Paulus, M. (2009). New insights into symptoms and neurocircuit function of anorexia nervosa. Nature Reviews Neuroscience, 10, 573–584. https://doi.org/10.1038/nrn2682

Treasure, J., Duarte, T. A., & Schmidt, U. (2020). Eating disorders. The Lancet, 395(10227), 899–911. https://doi.org/10.1016/S0140-6736(20)30059-3

Gaudiani, J. (2019). Sick Enough: A Guide to the Medical Complications of Eating Disorders. Routledge.

Urbina, J., Salinas-Ruiz, L. E., Valenciano, C., & Clapp, B. (2026). Micronutrient and nutritional deficiencies associated with GLP-1 receptor agonist therapy: A narrative review. Clinical Obesity, 16, e70070. https://doi.org/10.1111/cob.70070