Hormones and Calories

Something I have found interesting looking at different topics and interests is how the body regulates hormone creation based on calories. I do not think it is necessarily calories to say rather that the loss of mass from adipose tissue likely signals to downregulate other hormones somehow. A prime example is Sex Hormone Binding Globulin (SHBG).

Google Gemini defines SHBG as "a protein produced mainly by the liver that binds to sex hormones like testosterone and oestradiol in the blood, making them inactive."

Recent review into the protein found at DOI: 10.1002/mnfr.202400020 is able to give the following insights when reviewed and cross reviewed with chatgpt.

1. Mechanisms of SHBG regulation

a) Hepatic lipid metabolism / hepatic fat content

• One mechanism: increased hepatic lipogenesis / increased liver fat appears to reduce SHBG production. Conversely, reduction of liver fat and lipogenesis tends to increase SHBG.

• For example, the transcription factor HNF‑4α is involved in hepatic SHBG gene expression; when lipogenesis is high, HNF-4α expression is lower, thus SHBG is lower.

• Lipid-sensing nuclear receptors (e.g., PPAR‑γ) also play a role: PPAR-γ activation tends to suppress SHBG in hepatocytes.

b) Insulin / metabolic signalling

• Low SHBG is seen in insulin resistance, obesity—so insulin/metabolic state plays a role. The review notes diet influences insulin sensitivity, which then may influence SHBG.

• Inflammatory cytokines and metabolic stress also down-regulate SHBG production via hepatic pathways.

c) Nutrient signalling / specific dietary compounds

• Apart from broad macronutrient shifts, specific nutrients or bioactive compounds (monounsaturated fats, polyphenols, caffeine) may up- or down-regulate SHBG production via gene regulatory mechanisms (promoter activation, receptor binding).

  • Example: The review references work where the polyphenol Resveratrol increased SHBG via the constitutive androstane receptor (CAR) in hepatocytes.

  • Another example: oleic acid (a MUFA) increased SHBG production in vitro via down-regulation of PPAR-γ.

    
    

2. Nutritional / dietary factors influencing SHBG

i) Caloric intake / energy balance

• Diets that result in excess hepatic lipogenesis (excess calories, especially from sugars/fructose) may lower SHBG.

• Conversely, caloric restriction and improving metabolic health may increase SHBG (via reducing hepatic fat). The review alludes to this general pattern.

ii) Composition of fats (type of fat)

• Monounsaturated fatty acids (MUFAs), especially oleic acid (e.g., from olive oil) are associated with higher SHBG levels. For example men using olive oil had higher SHBG compared to sunflower-oil users.

• Saturated fats correlate negatively with SHBG in some studies.

• The review suggests diets rich in healthy fats (MUFAs) may promote SHBG via hepatic gene regulation.

iii) Carbohydrates / sugar / fibre

• High ingestion of simple sugars, especially fructose/glucose leading to hepatic de-novo lipogenesis may reduce SHBG by promoting hepatic fat accumulation. (The review mentions high sugar → liver fat → lower SHBG).

• Fibre and complex carbohydrate intake, which improve insulin sensitivity/lower hepatic fat, may favour higher SHBG, though the review emphasises the need for more mechanistic study.

iv) Bioactive compounds / dietary pattern

• Mediterranean-type dietary pattern: with olive oil, red wine polyphenols, high fibre, etc — the review suggests this pattern is associated with higher SHBG.

• The review mentions caffeine (and other bioactives) as potentially increasing SHBG in some contexts.

• Red wine / resveratrol: the review gives specific example: resveratrol increased SHBG via CAR activation.

v) Protein intake

• Some observational evidence links higher protein/fibre/healthy fat diets with higher SHBG; the review mentions that dietary protein content is among the macronutrient variables that affect SHBG.

  
  

3. Clinical / practical implications

• Because low SHBG is associated with metabolic disorders (obesity, insulin resistance, type-2 diabetes, cardiovascular disease) the ability to raise SHBG via diet may have beneficial metabolic implications.

• For hormone-dependent tissues (e.g., muscle, adipose, reproductive tissues) the availability of free sex hormones is influenced by SHBG. Thus diet-induced changes in SHBG might influence muscle mass, fat distribution, androgen/estrogen signalling.

• In individuals with metabolic dysfunction (or athletes with high loads, body composition goals) the manipulation of diet to favour higher SHBG might promote better hormone milieu and metabolic health.

• However, the authors caution that the mechanistic evidence is still incomplete, especially human interventional studies targeting specific nutrients and measuring SHBG as an endpoint. They call for more research.

  
  
  
  

6. Limitations / caveats from the review

• Most data are observational, not always interventional. The review emphasises that while many associations exist (diet vs SHBG), the causal/ mechanistic pathways especially in humans are still emerging.

• Many studies do not separate types of nutrients (e.g., types of fats) in detail.

• Individual variability is substantial: genetics, liver status, hormonal milieu, insulin sensitivity will moderate response.

• The review does not provide specific “doses” of nutrients that reliably alter SHBG in humans (yet).

  
  

7. Summary bullets

• SHBG is a gate-keeper of sex steroid availability.

• Diet influences SHBG via hepatic fat/lipogenesis, insulin/metabolic state, and specific nutrient-gene regulatory mechanisms.

• Diet patterns such as high MUFAs, fibre, Mediterranean-style, moderate bio actives like resveratrol/caffeine are associated with higher SHBG.

• Diets high in simple sugars, saturated fats, or with high hepatic fat are associated with lower SHBG.

• The evidence is still evolving; more interventional work is required.

  
  

References

Brianso-Llort L, Saéz-Lopez C, Alvarez-Guaita A, Ramos-Perez L, Hernandez C, Simó R, Selva DM. Recent Advances on Sex Hormone-Binding Globulin Regulation by Nutritional Factors: Clinical Implications. Mol Nutr Food Res. 2024 Jul;68(14):e2400020. doi: 10.1002/mnfr.202400020. Epub 2024 Jun 27. PMID: 38934352.