More High Protein Diet Dangers — Low Tryptophan, Low Serotonin, Insulin Resistance

Discussions continue on The CR Society’s list about the best diets for glucose control.  Some advocate high protein diets; however, the self-reported results I’ve seen often indicate insulin resistance.

But why? One answer may be rooted in tryptophan uptake and the pathway it supports, which stimulates insulin production.

If you eat a high protein diet – and some do it in hopes of having “balanced” amino acid intake, you won’t get a balance at all: Absorption of the amino acid tryptophan is prevented by other competing amino acids. Here’s more about it:

Effects of normal meals rich in carbohydrates or proteins on plasma tryptophan and tyrosine ratios.

Wurtman RJ, Wurtman JJ, Regan MM, McDermott JM, Tsay RH, Breu JJ.

American Journal of Clinical Nutrition. 2003 Jan;77(1):128-32

PMID: 12499331, NIH, NLM, PubMed access to MEDLINE biomedical citations

See the full abstract:

A telltale sign of decreased tryptophan absorption is sleep quality, which relies on healthy uptake of tryptophan through the blood brain barrier for conversion to serotonin and then to melatonin.

One of the worst aspects of low serotonin is depression. An inability to stick with a diet goes along with this since serotonin levels can determine satiety. This is why The CR Way to Happy Dieting, the multimedia e-Book that is provided as a download to Healthful Weight Loss members, emphasizes serotonin-producing recipes.

Serotonin plays important roles in may of the body’s organs including pancreatic B cells, which are responsible for making insulin.

Convergence of the insulin and serotonin programs in the pancreatic β-cell.

Ohta Y, Kosaka Y, Kishimoto N, Wang J, Smith SB, Honig G, Kim H, Gasa RM, Neubauer N, Liou A, Tecott LH, Deneris ES, German MS.

Diabetes Center, University of California, San Francisco, San Francisco, CA, USA.

Diabetes. 2011 Dec;60(12):3208-16.



Despite their origins in different germ layers, pancreatic islet cells share many common developmental features with neurons, especially serotonin-producing neurons in the hindbrain. Therefore, we tested whether these developmental parallels have functional consequences.


We used transcriptional profiling, immunohistochemistry, DNA-binding analyses, and mouse genetic models to assess the expression and function of key serotonergic genes in the pancreas.


We found that islet cells expressed the genes encoding all of the products necessary for synthesizing, packaging, and secreting serotonin, including both isoforms of the serotonin synthetic enzyme tryptophan hydroxylase and the archetypal serotonergic transcription factor Pet1. As in serotonergic neurons, Pet1 expression in islets required homeodomain transcription factor Nkx2.2 but not Nkx6.1. In β-cells, Pet1 bound to the serotonergic genes but also to a conserved insulin gene regulatory element. Mice lacking Pet1 displayed reduced insulin production and secretion and impaired glucose tolerance.


These studies demonstrate that a common transcriptional cascade drives the differentiation of β-cells and serotonergic neurons and imparts the shared ability to produce serotonin. The interrelated biology of these two cell types has important implications for the pathology and treatment of diabetes.

PMID:22013016, NIH, NLM, PubMed access to MEDLINE biomedical citations

It’s easy to see why excessive protein intake, which reduces serotonin production, could cause serious health problems including poor glucose control.

You can read more about high dietary protein and its ability to negate CR biochemistry in this forum post on

Why a high protein diet may contribute to insulin resistance



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