BEWARE: The Ketogenic Diet Used as an Intervention for Bipolar Disorder or Schizophrenia Raises LDL!

(A commentary on a double standard hiding in plain sight)

So let me get this straight: it's the dietary intervention that needs the health warning? 🤔

That question was prompted by a post from Dr Chris Palmer — Harvard psychiatrist and one of the leading voices in metabolic psychiatry — who noted something rather inconvenient: evidence-based treatments for schizophrenia and bipolar disorder often lead to increases in LDL cholesterol. And we prescribe them to millions of patients anyway.

He's right. And the implications are worth sitting with.

What the Evidence Actually Says

We prescribe medications to millions of people with schizophrenia and bipolar disorder that demonstrably raise LDL cholesterol and triglycerides in many cases, cause significant weight gain, or even increase the risk of type 2 diabetes. These are not rare or disputed findings — they are well-documented metabolic effects of many second-generation antipsychotics, including some of the most widely prescribed.

Evidence-based. Guidelines-approved. No further questions.

Forest plot of antipsychotic drugs vs. placebo for the primary outcome “weight gain”. Network meta-analysis estimates of treatment effect of each drug vs. placebo are reported as mean differences (MDs) and 95% credible intervals (CrIs). The order of treatments is according to surface under the cumulative ranking curve (SUCRA) ranking. LAI – long-acting injectable, AMI – amisulpride, ARI – aripiprazole, ASE – asenapine, BRE – brexpiprazole, CAR – cariprazine, CLO – clozapine, CPZ – chlorpromazine, FLP – fluspirilene, FLU – fluphenazine, FPX – flupentixol, HAL – haloperidol, ILO – iloperidone, LUR – lurasidone, OLA –

Now consider what happens when someone's LDL rises on a ketogenic diet being trialled as a metabolic intervention for the same conditions. Suddenly, we have a side effect problem. The alarm bells ring. The caveats multiply. The intervention is regarded with suspicion.

The double standard is not subtle. It is not even trying to be.

Why This Matters

The ketogenic diet is attracting serious scientific interest as a potential metabolic intervention in psychiatry — not as a fringe idea, but as a hypothesis being tested in peer-reviewed clinical trials. The rationale is grounded in mitochondrial function, glucose metabolism, and neuroinflammation. Early results in bipolar disorder and schizophrenia are, to put it mildly, interesting.

Does the ketogenic diet raise LDL in some people? Yes, it can — and this should absolutely be monitored. But the elevation is not universal, it is often transient, and — critically — it must be contextualised against a broader cardiometabolic picture that, for many people on a well-formulated ketogenic diet, tends to improve rather than worsen: triglycerides fall, HDL rises, insulin sensitivity improves, inflammatory markers frequently decline.

Cholesterol arithmetic is not cardiovascular risk arithmetic. The two are related but not interchangeable, and anyone working in this space should know the difference.

The Inconvenient Comparison

The medications we have been prescribing for decades are not metabolically neutral. Many of them carry real, measurable, and well-documented risks — risks that we have collectively decided are an acceptable trade-off for symptom management. That is a legitimate clinical judgement. But it should make us more curious about alternatives, not less.

If we are genuinely concerned about LDL, we should be equally concerned about it regardless of the cause. The fact that we are not — that medication-induced dyslipidaemia attracts far less scrutiny than dietary-induced dyslipidaemia — tells us something about the filters through which we evaluate evidence.

A Note on Nuance

None of this is an argument against medication. Antipsychotics save lives and prevent profound suffering. The point is not to dismiss them — it is to hold dietary interventions to a comparable standard of honest assessment, rather than a higher one.

If a patient's LDL rises modestly on a ketogenic diet while their psychiatric symptoms improve, their weight decreases, their triglycerides fall, and their insulin sensitivity recovers — that is a conversation worth having with a clinician who can look at the whole picture. It is not, in itself, a reason to abandon an intervention that may be offering meaningful benefit.

What to Take Away

The question Dr Palmer raises is a sharp one, and it deserves a sharp answer. We apply different levels of scrutiny to different interventions, and that asymmetry is not always scientifically justified. It is sometimes cultural, sometimes institutional, and sometimes simply a matter of what we are accustomed to accepting.

Metabolic approaches to psychiatric conditions are not going away. The research is building. The clinical interest is real. And the patients who are benefiting are not interested in waiting for a consensus that moves slower than their suffering.

Worth reading the study. Worth asking the question. Worth noticing the double standard.

REFERENCES:

• Longhitano C, Finlay S, Peachey I, Swift J-L, Fayet-Moore F, Bartle T, Vos G, Rudd D, Shareef O, Gordon S, Azghadi MR, Campbell I, Sethi S, Palmer C, Sarnyai Z. The effects of ketogenic metabolic therapy on mental health and metabolic outcomes in schizophrenia and bipolar disorder: a randomized controlled clinical trial protocol. Frontiers in Nutrition. 2024;11:1444483. https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2024.1444483/full

• Burschinski A, Schneider-Thoma J, Chiocchia V, Schestag K, Wang D, Siafis S, Bighelli I, Wu H, Hansen W-P, Priller J, Davis JM, et al. Metabolic side effects in persons with schizophrenia during mid- to long-term treatment with antipsychotics: a network meta-analysis of randomized controlled trials. World Psychiatry. 2023. doi:10.1002/wps.21036

• Palmer CM. LinkedIn post https://www.linkedin.com/in/christopher-palmer-01713032/

This is not a medical advice.

If you are considering any dietary intervention for a health condition, always work with a qualified practitioner who can assess your individual picture — including full lipid panels, metabolic markers, and clinical context.