TNF-alpha: Inflammation and Your Genes

Do you feel like you are always dealing with inflammation? Joint pain, food sensitivity, etc? Perhaps your body genetically gears towards a higher inflammatory response. Tumor necrosis factor (TNF) is an inflammatory cytokine that acts as a signaling molecule in our immune system. In an acute inflammatory situation, TNF-alpha plays an essential role in protecting us.

What is Tumor Necrosis Factor- Alpha?

TNF-alpha is an inflammatory cytokine produced by the immune system cells (macrophages) during acute inflammation. The main role of this cytokine involves signaling for ‘apoptosis’ meaning the cell needs to be destroyed.[ref]

We think of redness, swelling, heat, and pain with inflammation such as after getting a cut or wound. The inflammatory response is also important for fighting off bad bacteria, viruses, or fungus.  When the body needs an inflammatory response to fight off an invader, it releases cytokines, such as TNF-alpha (and others).

When TNF-alpha binds to its receptor on the surface of a cell, one option is that kills the cell. Kind of like it pulls the pin on a grenade. Another option is that it can also cause the cell to produce other inflammatory response molecules, but the cell still survives.

While cell death sounds bad, it is completely necessary to fight off certain infections or if a cell is cancerous.

In fact, some of the genetic variants that increase TNF-alpha levels are linked to being better able to fight off pathogens, such as malaria.

But that superpower of fighting infection comes with a price.  Chronically elevated levels of TNF-alpha are linked with a lot of autoimmune diseases. The same genetic variant that helped your ancestors survive an infection (and thus live to pass on the variant to you), could be at the root of many of the inflammatory conditions that plague us today.[ref]

Higher TNF-alpha is linked to:

  • rheumatoid arthritis
  • psoriasis
  • ulcerative colitis
  • Crohn’s disease
  • skin infections
  • gum disease
  • asthma
  • diabetic ulcers
  • heart disease
  • septic shock
  • depression

TNF Gene Variants:

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There are several genetic variants linked to naturally more active TNF-alpha.

Check your genetic data for rs1800629 (23andMe v4, v5; AncestryDNA):

  • A/A: higher TNF-alpha levels, more inflammation – see risks below
  • A/G: higher TNF-alpha levels – see risks below
  • G/G: typical, better response to high protein/low carb diet

Members: Your genotype for rs1800629 is .

Studies on rs1800629 (also known as -308) show:

  • Higher risk of: ulcerative colitis[ref] celiac disease[ref] (note – must have HLA type also), septic shock[ref], diabetic foot ulcers[ref], asthma[ref] , Hashimoto’s thyroiditis[ref], skin infections[ref], periodontitis[ref], asthma[ref] in children, COPD[ref], stroke[ref], gum disease[ref]
  • Lower risk of:  Malaria (half the risk)[ref], osteoporosis[ref],  stroke[ref]


Check your genetic data for rs361525 (23andMe v4, v5; AncestryDNA):

  • A/A: higher TNF-alpha levels[ref], increased risk of psoriasis[ref], asthma[ref], COPD[ref]
  • A/G: somewhat higher TNF-alpha levels
  • G/G: typical

Members: Your genotype for rs361525 is .


Check your genetic data for rs1799964   -1031T>C  (23andMe v4, v5; AncestryDNA):

  • C/C: (usually) higher TNF-alpha levels[ref][ref], increased risk of IBD[ref], lupus[ref], gum disease[ref]
  • C/T: somewhat higher TNF-alpha levels
  • T/T: typical – generally not at higher risk for inflammatory diseases

Members: Your genotype for rs1799964 is .

Check your genetic data for rs1799724 (23andMe v4, v5):

  • T/T: (generally) higher TNF-alpha levels[ref][ref]
  • C/T: (generally) higher TNF-alpha levels
  • C/C: typical – generally not at higher risk for inflammatory diseases

Members: Your genotype for rs1799724 is .



Rosmarinic acid (found in rosemary, basil, holy basil, lemon balm, and perilla oil) is a natural TNF-alpha inhibitor.[ref] In addition to adding herbs to your food, holy basil can be found in a tea (called Tulsi tea) or as a supplement. has good information on rosmarinic acid.

Curcumin is another natural TNF-alpha inhibitor.[ref] Turmeric is a spice that is a good source of curcumin in the diet; curcumin supplements are also available and may be easier to take on a daily basis

Probiotics containing Bifidobacteria or Lactobacillus may decrease TNF-alpha levels.[ref] One study showed that B. adolescentis decreased TNF-alpha levels and had an antidepressant effect.[ref] In kids with celiac disease, Bifidobacterium breve BR03 decreased TNF-alpha levels.[ref] Lactobacillus Plantarum has shown to restore tight junctions (decrease leaky gut) in the intestines. It is also decreased TNF-alpha.[ref]

Aged garlic extract was shown in a study to decrease TNF-alpha levels by 35%.[ref][ref] You can find aged black garlic at grocery stores, and it is available as a supplement online if you don’t like the taste of aged garlic.

Glycine has been shown to reduce TNF-alpha and inflammation.[ref] Glycine is an amino acid that is abundant in bone broth, collagen, and gelatin. My favorite way to increase my intake of gelatin is to dissolve it in my coffee each morning.

Magnesium: Low magnesium levels may play a role in higher TNF-alpha levels. Magnesium sulfate, in conjunction with thyroid medication, in hypothyroid rats, decreased TNF-alpha levels.[ref][ref]

Related Articles and Topics:

CTLA-4: Autoimmune Genetic Risk
The CTLA4 gene codes for a protein that is important in the immune system. It acts as a checkpoint that can downregulate your immune system response. Genetic variants in the CTLA4 gene can increase your risk for several different autoimmune diseases.

Psoriasis Genes
Psoriasis is an autoimmune condition that causes dry, sometimes itchy patches of skin. It is caused by the immune system attacking your skin cells, speeding up the turnover of the cells. Genetics plays a role in your susceptibility

Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.