This post is part of a series about immune balance. It goes over the Th2 response, diseases associated with its overactivity, and complementary approaches – including lifestyle, food, and supplements – that may help keep the immune system in good health.
Achieving Immune Balance
When to See a Doctor
If your goal is to lower your Th2 response because you have serious allergy-related problems – including asthma and severe eczema – it’s important to talk to your doctor, especially if your symptoms are significantly impacting your daily life.
Your doctor should diagnose and treat any underlying conditions causing your symptoms.
Complementary Approaches
Before we talk about the Th2 system in detail, we’ll outline all the complementary approaches that people can be presented with.
Many people just want the bottom line. That’s why we’ve started off with this list. It includes some mechanisms that scientists are investigating in cells and animals but that haven’t been proven in humans.
- Sun/UVB light [1] – UVB decreases IFNy in Th1 dominance but increases it in Th2 dominance. So it’s balancing. It also decreases IgE responses. UVA in the sun also decreases Th2 dominance [2].
- Probiotics… Decreases Th2: L Reuteri [3] (probiotic), L. Plantarum [4] (probiotic), L. salivarius [4] (probiotic), L. lactis [4] (probiotic)… Increases Th1: S Boulardii? [5], L. Sporogenes, L Acidophilus [6], L casei [7], Lactobacillus rhamnosus GG [8], Lactobacillus paracasei [9], Lactobacillus salivarius [9], B Longum [10], L Brevis [11], L fermentum [12].
- NAC/Glutathione sufficiency decreases Th2 [13] and increases Th1 [14].
- Licorice -18/β-glycyrrhetinic acid+LicoA [15, 16]. Glycyrrhizin increases IFNy and decreases the Th2 response [17, 18].
- Gynostemma [19]. This is a Th1 immune stimulant and reduces allergies. Gynostemma is recommended also because it’s a powerful mitochondrial enhancer.
- Ginger or juice the root [20, 21]. Recommended because it has anecdotal support in addition to the research, but also because you can get it everywhere, it has a long history of use and for its multitude of other benefits.
- Reishi [22]
- Tinospora [23]. This has a clinical trial backing it, with some anecdotal support.
- Quercetin [24]
- Astragalus [25] Decreases Th2 and increases Th1.
Anecdotally, people report starting with one supplement at a time to rule out reactions. Aside from any potential effects on Th2 immune dominance, many of these supplements are also thought to strengthen immune defense and may have other beneficial aspects to them.
If you suspect you are Th1 and Th2 dominant, then read this post.
Limitations
Remember that the existing evidence does not suggest that Th2 dominance causes allergies. Complex allergic disorders always involve multiple possible factors – including biochemistry, environment, health status, and genetics – that may vary from one person to another.
Therefore, you may try the strategies listed above if you and your doctor determine that they could be appropriate. Read through the approaches we bring up and discuss them with your doctor before trying them out. This is particularly important if you plan to take any dietary supplements.
Most of the lifestyle, dietary, and supplement factors listed in this article rely on animal and cellular data. These findings can’t be applied to humans. Clinical research is needed before the safety and effectiveness of any approach listed in this post is determined.
Thus, we’re providing a summary of the existing research, which should guide further investigational efforts. However, the studies listed should not be interpreted as supportive of any health benefit.
Additional Precautions
Supplements have not been approved by the FDA for medical use and generally lack solid clinical research. Regulations set manufacturing standards for them but don’t guarantee that they’re safe or effective.
Additionally, supplement-drug interactions can be dangerous and, in rare cases, even life-threatening. That’s why it’s so important to consult your healthcare provider before supplementing and let them know about all drugs and supplements you are using or considering.
Dosage may also matter and different doses will have different effects on Th1/Th2 balance. Safe supplement doses should not be exceeded.
Finally, have in mind that none of these strategies should replace what your doctor recommends or prescribes.
What is Th1 vs Th2?
The Basics
To start with, the human immune system is incredibly complex. We have many types of immune cells that are orchestrated by various factors – from our encounter with microbes, to our health status, genetics, mood, and more.
The Th1/Th2 theory is one attempt at understanding immune regulation, and T-Helper 1 (Th1) and T-Helper 2 (Th2) cells are its key players.
This theory dates back to studies on mouse immune cells in the 80s. However, it is still considered controversial and it’s not without limitations and discrepancies. More large-scale human studies are needed to determine its validity [26].
According to the Th1/Th2 theory [26]:
- Th1 cells drive the so-called type-1 pathway (“cellular immunity”). They are thought to be involved in fighting viruses and other pathogens that enter cells, getting rid of cancerous cells, and triggering delayed-type hypersensitivity (DTH) skin reactions.
- Th2 cells drive the type-2 pathway (“humoral immunity”). They are hypothesized to increase antibody production and fight invaders that are outside cells. They may be involved in tolerance of organ transplants (xenografts) and of the fetus during pregnancy
Th1 cells produce mainly the cytokines or messengers IL-12 and interferon gamma and Th2 cells produce mainly IL-4. Both types of cells produce other cytokines as well [26].
Inconsistency Issues
The Th1/Th2 theory states that overactivation of either the Th1 or the Th2 pattern can cause disease. According to one interpretation, people’s immune systems often tilt to Th1 or Th2. Similarly, either pathway is thought to down-regulate the other [26].
One of the reasons why an increase in one may translate to a decrease of the other is because they differentiate from a progenitor or original cell (Th0) and there’s a limited number of these cells.
The Th1 side is seen as more immune-stimulatory, while the Th2 side is considered to be more “immune-deficient.” However, both can produce “inflammation” in certain situations.
Based on this, some studies claim that most substances that decrease Th1 will increase Th2 and vice versa (decrease Th1 will increase Th2), but this isn’t always the case.
Some nutrients – including long-chain omega-3 fatty acids (EPA and DHA) seem to improve various inflammatory and autoimmune conditions without any specific Th1/Th2 effect [26].
Often, it’s uncertain whether a certain nutrient or intervention stimulates the Th1/Th2 immune system or not.
Additionally, many diseases that were previously classified as Th1- or Th2-dominant failed to meet defined criteria. Plus, Th1 dominance can be polarized to Th2 patterns, and vice versa [26].
The main issue with the whole Th1/Th2 theory, as some scientists have recently pointed out, is that the activity of cytokines and other immune messengers rarely fall into strict Th1 or Th2 patterns. Some cells, like non-helper regulatory T cells (Tregs), may influence (and likely suppress) both Th1 and Th2 responses [26, 27, 28].
Factors that May Balance the Immune System (Lower Th2)
We’re providing a summary of the existing research, which should guide further investigational efforts. The studies listed below were mostly done in animals and should not be interpreted as supportive of any health benefit in humans.
Thus, please read through the factors below having all the limitations and precautions mentioned above in mind.
Lifestyle/Hormones/Pathways
- High-intensity exercise [29]
- Cold exposure (Antarctic winter) [30]
- Oxytocin (decreases IL-4) Falling in love, having sex, nursing, and positive social encounters increase oxytocin [31]. L Reuteri is also being researched for increasing oxytocin [32]
- LLLT [33]
- Inhibiting mTOR.
Foods
- Kiwi [34]
- Black rice [35]
- Rice [36]
- Rice Bran Oil [37]
- Cocoa [38]
- Black Cumin Seed Oil [39]
- Coffee (in moderation) [40]
- Bee products: Royal Jelly [41], Bee Pollen [42] Propolis, YS Royal Jelly/Honey (may increase Th1 and TNF-alpha) [43, 44]
- Black pepper [45]
- Prebiotics [46], FOS and GOS (prebiotics) [47]
- Adequate intake of vitamin B(6), folate, B(12), C, E, and of selenium, zinc, copper, and iron [48]. These may also support healthy immune defense.
Other (Experimental)
The following factors are theoretical and anecdotal. They aren’t backed up by solid science. We bring them up for informational purposes.
- Vitamin A/Retinol [49] (IL-4, IL-13)
- Genistein [50, 51]
- Chondroitin sulfate [52]
- Spirulina [53] – without increasing Th1
- Oregano oil/Carvacrol [54]
- Theanine [55] – decreases a th2 type immune response
- Luteolin [56]
- Resveratrol [57]
- Theaflavins [58] (found in black tea)
- Apple polyphenols [59]
- Lycopene [60] (in tomatoes)
- Lutein [61]
- Fenugreek [62]
- Baicalin/Chinese Skullcap [63]
- Rutin [64]
- Fisetin [65, 66]
- Ashwagandha [67]
- Ginseng (Asian) [68] – Seen as mostly stimulating but also regulating. Being researched for affecting TNF-α, IL-1β, IL-6, and IFN-γ (produced by macrophages) and raising IL-2, IFN-γ, IL-1α, and GMC-SF (produced by sleep cells).
- Grape Seed Extract [69, 70], but animal studies point to decreased Th1 cells in certain experimental conditions like Rheumatoid Arthritis [71]
- Red Wine Polyphenols [72]
- The following are thought to increase Th1: Colostrum [73], Bilberry [74], Icariin [75], and Lion’s Mane
- Andrographis [76]
- Beta Glucans [77] – found in mushrooms and being investigated for inhibiting TNF [78].
- Schisandra [79], Deer Antler Velvet [80], Chrysin [81], Burdock root [82], Cordyceps [83], Ecklonia cava [84], Butterbur, Bamboo extract [85]
- Gallic acid [86]
- Kaempferol [87]
- Caffeic acid (found in coffee, green coffee extract, apples, artichoke, berries, and pears, wine) [88, 89]
- Curcumin [57] – contradictory [90]
- Epigenetics: mir-27b [91], mir-128 [91], mir-135b [91], mir-155 [91], mir-340 [91]
The following might lower Th2 but should be avoided because of numerous detrimental health effects: Nicotine [92], Choline deficiency [93], and Zinc deficiency [94].
Factors that May Disrupt Immune Balance & Raise Th2
You can take a peek at this post to learn about factors that may reduce Th1 activity. Not all of those factors will raise Th2 dominance and some are good for general well-being.
It’s always a good idea to avoid unhealthy habits – such as smoking, fast food, overeating, being under a lot of stress, and drinking too much – that can bring your immune system out of balance. Look to get regular exercise, enough nutrients, sleep, and follow a healthy circadian rhythm.
Lifestyle
- Circadian Disruption
- Severe injury [95]
- Mold, Mycotoxins [96]
- Diesel exhaust particles [97]
- Magnesium deficiency [98]
- Fine-ambient particles [99]
- BPA [100]
- Mercury poisoning [101, 102]
- Glutathione depletion [13]
- Chronic psychological stress [103]
- Excess Vitamin D3 [104]
Addictive/Illegal Substances
The following are addictive and/or illegal substances that should be avoided:
*THC may reduce pain in MS and is also being researched in people with nausea, insomnia, and seizures. However, its use remains controversial because of the high risk of addiction, dependence, side effects, and withdrawal syndrome (particularly with non-medical use). The use of cannabis is illegal under federal law in the US.
Hormone- and Neurotransmitter-Related (Experimental)
Have the following in mind first:
- Corticosteroids, hormones, and other medications should only be used with a doctor’s prescription.
- Pregnenolone is an unapproved drug with a high potential for harm.
- Brain chemistry is not something that people can change on their own with the approaches listed blog posts.
Additionally, the following hormonal factors and neurotransmitters are theoretical. They aren’t backed up by solid science. We bring them up for informational purposes.
- Glucocorticoids [109]
- Estrogen [110]. Inhibits IL-12, TNF-alpha, and IFN-gamma, and increases IL-10, IL-4, and TGF-beta. Plant-based foods have phytoestrogens, especially soy.
- Progesterone [111]
- TRH [112]
- Insulin [113]
- Serotonin [114] 5-htp is a precursor
- Dopamine [115, 115], L-dopa/mucuna is a precursor
- Histamine [116]
Human data are lacking.
Pathways
Scientists are investigating whether the following pathways reduce Th2 patterns in animals and cells: Nrf2 [117]PGE2 [111], DPP-4 inhibitors [118], Nitric oxide scavenging [119], IL-4, IL-2, STAT-6, GATA-3, mir-21 [120], mir126 [120, 13].
Diet
Supplements
The following supplements are not thought to be immune disruptors. Researchers are investigating whether they can suppress Th2 activity in animals or cells:
- Red Yeast Rice/Lovastatin [125]
- Hi-Maize /Butyrate [126] (via inhibiting IL-12 and increasing IL-10)
- Licorice -18β-glycyrrhetinic acid [127]
- Vitamin E – mixed findings [128]
- Grapeseed Extract G [71], contradictory findings [69]
- Olive leaf extract [129]
- Fulvic + humic acid [130]
- Honokiol [131]
- Boswellia [132]
- LDN [133] – low dose naltrexone
- Chrysin [134]
- Emodin [135]
- Vitamin E [128]
- Black Cumin Seed Oil – aqueous [136]
- Inositol [137]
- Astragalus – increased number of Th2 cells [138]
- Feverfew/parthenolide [127]
- Andrographis [139] – contradictory [76]
- Ursolic acid [127]
- St John’s Wort/Hyperforin [140]
- β-sitosterol [127] (in plants, saw palmetto)
- Stinging nettle [141] (IL-4)
- Creatine [142]
- Naringin [143]
- Hesperidin [144]* Mixed effects [145]
- Theanine+NAC [146]
- Echinacea [147, 148]
- Chinese Skullcap/Baicalin [63, 149] (IL-4, IL-5, TGFb, IL-10)
- Eucalyptol [127], Limonene [127], Thymol [127]
- Cat‘s claw [150]
- B. fragilis [151] (common probiotic)
Many of these studies had mixed results and human data are lacking. Th1/Th2 theory inconsistencies and limitations may explain these conflicting findings.
Remember, a certain substance can increase some Th2 cytokines and decrease others. It may both suppress Th1 and Th2 or stimulate both systems [26].
Scientists agree that any attempt to divide the human immune system into two strict Th1/Th2 parts is doomed to fail [26].
Plus, some of these supplements can be safely used under medical guidance. Some support immune health. Check with your doctor if you’re taking any of the supplements mentioned above.
