TNF

If you have an immune systemdisease like rheumatoid arthritis(RA), you may have heard your doctor use the term TNF. It’s shorthand for tumor necrosis factor, a substance in your body that causes inflammation, or swelling.

It may surprise you to learn that inflammation can be a good thing. It happens when your immune system -- your body’s natural defense force -- is fighting a possible threat. For example, when you have a cold, your sinuses swell. When you get a cut, your finger turns warm and red. These things don’t feel good, but they show your immune system is doing its job.

Sometimes, inflammation isn’t good for the body. If you have a disease like RA or psoriatic arthritis, your immune system is confused about what to attack. It goes after healthy body parts, like your joints, by mistake. Your system gets flooded with inflammation, which often means you have too much TNF -- specifically, a type called TNF alpha.

Inflammation Is a Chain Reaction

When you have an infection, certain white blood cells release key chemicals that tell other cells to cause inflammation. Your doctor might call them signaling chemicals. TNF is a major player when it comes to inflammation.

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Diet and Lifestyle to Inhibit TNF

One study found no difference in IL-6 or TNF in people who ate whole grains vs refined grains for 12 weeks (R). However, I’ve come across many studies that do show a reduction in inflammation with legume consumption (R, R2) — but obviously not for lectin sensitive people.

Interestingly, in men, red meat was associated with lower TNF (but was correlated with CRP in women) (R).

• Vagus nerve stimulation (R) – This is being researched as an alternative to MAbs.
• Ketosis (R)
• Acute psychological stress (R) and Glucocorticoids/Cortisol (R) (not recommended)
• Calorie restriction (R)
• Yoga (R)
• Tai Chi (R)
• Wim Hof Breathing/Meditation (R)
• Cycling/Exercise bike with desk (R)
• Mediterranean diet (R) – The resistant starch diet is an upgraded Mediterranean diet.
• Elemental diet  for lectin sensitive (R).
• Napping after sleep loss (R).
• Falling in love, having sex, nursing, and positive social encounters. All of these lead to increased oxytocin (R). L Reuteri also increases oxytocin (R).
• LLLT (R, R2, R3)

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What increases TNF?

• Oxidative stress – TNF activity is dependent on the generation of ROS(R).
• Lectins – For people who are lectin sensitive (perhaps a quarter of the population)
• Sun – Both UVA and UVB, which are emitted by the sun, acutely increase TNF-alpha (R, R2, R3). I still support sun exposure.
• Excessive exercise/Marathons (R)
• Sleep deprivation (R)
• Chronic insomnia – in the day time (R).
• Obesity (R)
• High glucose levels (R) – usually because of high glycemic index foods (R).
• A lack of exercise (R)
• A lack of resistant starch (R)
• Circadian disruption (R)
• Excess alcohol (R)
• Smoking (R)
• A high-fat diet (especially palmitic acid (R) – this doesn’t mean to eat a low fat diet) (R).
• A lack of foods like fruits and vegetables, which contain phytochemicals that inhibit TNF and other kinds of inflammation (R, R2).
• Heavy metals (R)
• Some toxins (R)
• Magnesium deficiency (R)
• Zinc deficiency (R)
• Vitamin D deficiency (R, R2, R3)
• Chromium deficiency (R)
• Choline Deficiency (R) – People who consumed more than 360 mg per a day had a 12% lower concentrations of TNF than those who consumed less.
• Coffee – Coffee drinkers had an average of 28% higher TNF, but maybe people with high TNF are tired, so they’re more likely to drink coffee. I got inflammation from it.
• Goji Berries (R), Aloe – (in cancer cells) (R), Reishi (R) – decreases if high (R), Andrographis (R), Apismin – found in honey and royal jelly(R). (I once took 20X the dosage of royal jelly and got fever from it). Arabinogalactan – (R).
• Vasopressin (R), IGF-1 (R), Angiotensin II (R).

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Top 16 Ways To Inhibit TNF

1. Elemental diet (R)/ Lectin avoidance diet if lectin sensitive
2. Fish Oil/DHA+EPA (R)
3. Calorie restriction (R)
4. Fasting (R)
5. Exercise (R)
6. PQQ (R)
7. Resveratrol (R)
8. Curcumin (R)…powerful (R)
9. EGCG (R)
10. Cinnamon/Sodium Benzoate (R, R2)
11. Black Cumin Seed Oil….powerful (R)
12. Rooibos (R)
13. Carob (R)
14. Licorice (R)
15. Nicotinamide Riboside NAD+ (R)
16. Kombucha/Lactic acid (R)
17. Hops (xanthohumol) (R)…potent.

You can check if your fatigue, mood, and motivation issues are related to TNF by measuring blood TNF-alpha levels.

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Tumor Necrosis Factor

The three most common inflammatory cytokines that are responsible for chronic inflammatory diseases are Tumor Necrosis Factor (TNF), Interleukin-1beta (IL-1b) and Interleukin-6 (IL-6). These are the most commonly talked about cytokines in the literature.

The transcription factor nuclear factor NF-kappaB is also heavily spoken about and these four proteins are what people most likely refer to when they talk about chronic inflammation (whether they are aware of this or not).

TNF can be increased in either Th1 dominance or Th2 dominance.

TNF increases CRP, which is a common blood measurement to gauge inflammation.  However, CRP is not sensitive enough to detect lower, but chronic levels of TNF.  See my discussion of this in my IL-6 post.

It’s important to realize that you can have TNF elevated locally in areas such as your hypothalamus or gut and it wouldn’t show on blood tests.

Many kinds of cells release TNF and then TNF goes on to stimulate other immune cells.

TNF is released by Macrophages, Dendritic cells, T cells, Fat cells, and Fibroblasts.

TNF then affects various cells. In particular, it will affect cells that line our blood vessels (endothelial cells), which causes vascular problems and this strongly causes cancer, as it causes angiogenesis and increased blood vessel formation (hypervascularization). It can also cause heart disease, kidney disease, and cognitive problems.

TNF negatively affects intestinal cells, causing cell death, leaky gut, IBS, and IBD.

TNF stimulates macrophages and effector T cells, which leads to more inflammatory cytokine production and apoptosis resistance (which contributes to cancer).

The Good

TNF induces sleep and it increases non-rem sleep (R).

Therefore, it’s good to have this elevated somewhat at night when we want to fall asleep. TNF is elevated naturally in healthy people at night time.

The duration of daytime sleep in Alzheimer’s disease correlated with the degree of functional impairment in the patient (R), which is a result of elevated inflammation.

Other examples of daytime sleepiness in chronic inflammatory states are Parkinson’s disease (R), traumatic brain injury (TBI) (R), stroke (R), heart failure (R), and type-2 diabetes (R).

TNF is a direct fat buster, which leads to insulin resistance in fat cells (R), but also insulin resistance in muscle cells (R). This means that glucosecan’t make its way into these cells.

TNF suppresses appetite by suppressing orexin (R, R2, R3).

So high levels of TNF makes you thinner by causing you to eat less and by inhibiting glucose into fat cells.

If you decrease TNF, you will become more hungry and store more fat.

Hence, it’s not surprising that anti-TNF therapy results in weight gain -an average of 5.5kg or 11 pounds in only 12 weeks (R).  It’s incredible that only one variable changed (TNF) and the study participants gained on average 11 pounds.

Low doses of TNF given to mice caused insulin and leptin resistance in the hypothalamus, which should contribute to obesity (R).

Even a relatively low level of TNF decreases aldosterone synthesis in response to ACTH (precursor of cortisol), which increases in response to stress and intense exercise (R). This can lower blood pressure.

Exercise increases ACTH, which normally tells our body to conserve saltby increasing aldosterone. However, if we have inflammation, then aldosterone production will be limited and if we sweat a lot it can cause low levels of salt in the body.

The Bad

I have already spoken about how I think trying to increase your motivation or mood by hacks, tricks, or by changing your mindset will only increase your neuroticism.

If you have elevated TNF and you bring it down, this will positively affect your mood and motivation.

TNF plays a major role in many diseases and is a cytokine that is a performance killer.

TNF can cause lasting harm by damaging your mitochondria (R).

TNF makes you tired, lowers your mood and decreases cognitive and physical performance by suppressing orexin (R, R2, R3).

Orexin is an extremely important neurotransmitter for many bodily functions.

Orexin performs a number of key roles in memory acquisition and consolidation, as well as in long-term memory reinforcement (R). Hence, if you have elevated inflammation, it will harm your cognitive performance (also by decreasing BDNF, etc).

TNF can also lower thyroid hormones, causing ‘low T3 syndrome’ (R). It can also lower testosterone (trended, but not significant) (R).

TNF slows wound healing, which means you’ll need more time to recover from exercise/injuries. (R, R2).

TNF can induce a ‘leaky gut’ (R).

Chronically elevated TNF-alpha can also disturb the circadian rhythmand cause fatigue in the day (R).

TNF can keep you from getting into ketosis (R).

When your natural skin fungus gets out of control, the body attacks it with cytokines that include TNF (also IL-6, IL-1b, IL-8), which recruits other aspects of the immune system (R).

Diseases Associated With TNF-alpha

• Autoimmune disease: in general (R), Multiple Sclerosis (R), Behcet’s(R), SLE (R), Scleroderma  (R), Sarcoidosis (R), Hidradenitis suppurativa (R), Ankylosing spondylitis (R), Erythema nodosumleprosum (R)
• Heart disease (R) – Heart failure (R), Atherosclerosis (R), Stroke (R)
• Cancer in general (R), Melanoma (R)
• Insulin Resistance (R), Diabetes II (R)
• Alzheimer’s (R), Parkinson’s (R), ALS (R)
• Major Depression (R) – Depressed people had TNF levels that were about 3.97 pg/ml higher than healthy people (R).
• IBS (R, R2), Crohn’s/Ulcerative Colitis (R)
• Rheumatoid Arthritis (R)
• Osteoporosis (R)
• Psoriasis (R), Eczema (R)
• Asthma (R), COPD (R). TNF  stimulates various molecules which recruit eosinophils, neutrophils, and lymphocytes to the airway. TNF can induce corticosteroid resistance (R).
• OCD – only sometimes (R),  Schizophrenia (R), Bipolar (R, R2), Anorexia (R)
• PCOS (R) – TNF shifts production of cortisol to testosterone, hence causing PCOS (R).
• Chronic Fatigue Syndrome (R), Fibromyalgia (R) – contradictory (R).
• Others: Tinnitus (R), Epilepsy (R), Cystic Fibrosis (R), Chemotherapy-induced neuropathy (R), Diabetic Neuropathy (R), Chronic liver disease (R), Fatty Liver (R)

The Most Significant Factors That Influence TNF

The two main factors that cause elevated TNF, if I had to guess, are lectins(R) and obesity (R), since fat cells produce TNF. If we ate less, a lot of people’s inflammation problems would disappear.

Other likely causes are sleep deprivation (R) and high blood glucoselevels (R) from eating too much, especially high glycemic index foods.

Other common factors are a lack of exercise (R), excess alcohol (R), smoking (R), and not enough fruits and veggies (R, R2).

UV acutely increases TNF (R, R2, R3) (but eventually downregulates it). This is the likely reason why some people experience fatigue from sunbathing.

Recent research indicates that TNF is potently inhibited by exercise (specifically, myokines or proteins produced by the muscles such as IL-6) (R). However, excessive exercise or Marathons will elevate TNF (R).

An infection can also elevate TNF. Bacterial (rather than viral) infections are more likely if you have elevated TNF (R).

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