Natural Killer Cells may be high or low in a variety of conditions. Scientists, therefore, suspect that they might contribute to some diseases and prevent others. Learn how low or high levels might impact health and what may change the levels of these cells in the body.
What Are Natural Killer (NK) Cells?
Overview
Natural Killer (NK) cells are described as a type of toxic lymphocytes that are critical to the immune system [1].
NK cells are produced in the bone marrow, lymph nodes, spleen, tonsils, and thymus, from where they then enter into the circulation [1].
Scientists think that they help quickly degrade stressed cells – such as tumor cells and virus-infected cells. NK cells are hypothesized to become active around 3 days after infection [1].
Studies suggest that NK cells develop long-lived and highly-specific memories to a variety of targets [2].
These cells are extremely diverse, as are genetic factors impacting them [3].
Function
According to recent scientific reviews, people who are genetically-deficient in NK cells have regular viral infections and die prematurely [4].
Individuals deficient in NK cells are prone to early phases of herpesvirus infection [5]. Since NK cells help to fight viruses like HIV, their deficiency may also worsen outcomes in HIV-positive patients [6]
Additionally, mice with poor NK cell function seem to be more prone to carcinogen-triggered cancers [3].
Activation of NK Cells
Scientists think that circulating NK cells remain in their resting phase until they are activated by cytokines. Once activated, they invade tissues with pathogen-infected cells and secrete cytokines such as interferons [7] and TNF-a to fight off the invader [7, 8].
NK cells also appear to release a membrane-disrupting protein, perforin, which causes cell death of the target cell. Perforin got its name because its thought to perforates the “skin” of the pathogen [7, 9].
When to See a Doctor
If your goal is to lower or increase your NK cells because you have serious health problems – including autoimmunity or severe allergies – 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.
Elevated Natural Killer Cells
Associated Conditions
Some studies covered in this section deal with associations only, which means that a cause-and-effect relationship hasn’t been established. Others rely on small sample sizes. The same goes for the associations listed under the “Low Natural Killer Cells” section.
Also, even if a study did find that high NK cells contribute to a certain condition like obesity or asthma, they are highly unlikely to be the only cause.
Complex health issues always involve multiple possible factors – including body and brain chemistry, environment, health status, and genetics – that may vary from one person to another.
The following have been associated with elevated NK cells in limited studies:
- Obesity, as NK can be overproduced in fat tissue [10]
- Insulin resistance, which is also linked with obesity and affects macrophages [11]
- Asthma, in which NK cells are thought to contribute to IgE-mediated immune-responses and worsen symptoms [7]
- Type 1 diabetes, in which NK cells are hypothesized to increase the destruction of the pancreas [7]
- Recurring miscarriages in women (an association) [12]
Th1 Dominance
Th1 dominance (IL-12, IL-2) is hypothesized to increase NK Cell activity [13].
On the other hand, NK cells may, in turn, destroy and suppress Th1 cells [14].
However, there are several gaps in the Th1/Th2 theory. Read more about it in this post.
Low Natural Killer Cells
Associated Conditions
- Cancer [7] – mixed findings; more consistent results were seen only in blood cancers [1]
- Viral infections (low number and activity) [7], since NK cells help fight off viruses.
- CFS (limited data point to low activity) [14]
- Multiple Sclerosis (low activity) [14]
- Rheumatoid Arthritis (low number and activity) [7]
- Lupus (low number and activity) [7]
Impairment of Natural Killer cells has also been associated with advanced aging in limited studies [15].
More research is needed to confirm and better understand these links.
Factors that May Increase Natural Killer Cells
Precautions
You may try the strategies listed in this article 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.
Supplements have not been approved by the FDA for medical use. Supplements 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. Always consult your doctor before supplementing and let them know about all drugs and supplements you are using or considering.
Most of the lifestyle, dietary, and supplement factors listed below rely on animal and cellular data. These findings can’t be applied to humans. Clinical studies are needed before the safety and effectiveness of any approach listed below are determined.
Lifestyle
Supplements
- Curcumin [18]
- Zinc [15]
- Selenium [15]
- Garlic [19]
- Astaxanthin [20]
- Melatonin [21]
- Astragalus [22]
- Amla/Gallic acid [23]
- Spirulina [24]
- Eleuthero [25]
- Danshen/Salvia Miltiorrhiza (proposed to be an alpha-glucosidase inhibitor that slows carb absorption) [26]
- Blueberry [27]
- Echinacea or Cichoric acid (from Echinacea) [28]
- Spleen [29]
- Thymus Peptides – for weakened immunity [29]
Pathways
The following hormonal factors and neurotransmitters are theoretical. They aren’t backed up by solid science. We bring them up for informational purposes.
Factors that May Raise Natural Killer Cell Function
Please read through the precautions mentioned above before making any changes to your lifestyle or supplements regimen.
The factors listed below are hypothesized to increase NK cell function but not necessarily NK cell levels.
Lifestyle
Supplements
These supplements are purported to be good for Th1-dominant people but still may stimulate NK Cells.
- Curcumin [39]
- Resveratrol [40]
- Andrographis [41]
- Ashwagandha [42]
- Magnesium [43]
- Cardamom [44]
- Probiotics: S. Boulardii [45], L. casei [46], L. bulgaricus [47]
- Vitamin B12 [48]
- Garlic (allicin) [19]
The following supplements are thought to be more suitable for people with a weak immune system:
- Thymus [49]
- Astragalus [50]
- Beta-Glucans [51]
- Goji Berries [52]
- Reishi [53]
- Gynostemma [54]
- Amla/Gallic acid
- Ginseng [55]
- Lion’s Mane [56, 57]
- Echinacea, Cichoric acid (from Echinacea) [28]
- Chlorella Tablets [58]
- GOS (galactooligosaccharides) [59]
- Germanium [60]
- Cocoacalm [61]
- CoQ10 – in older women, but not men [15]
- Vitamin E – in older women, but not men [15]
- Arabinogalactan [62, 63]
There is insufficient clinical evidence to support their use in people with immune deficiency.
Low dose naltrexone (LDN) was also researched for increasing NK cells, but its use is controversial [64]
Pathways
The following hormonal factors are theoretical. They aren’t backed up by solid science. We bring them up for informational purposes.
- T3 [65]
- Growth hormone [66]
- IGF-1 [66]
- Prolactin [66]
- MSH [67]
- Th1 activity: IL-12, IL-2 (CD56bright NK cells) [13]
Factors that May Reduce NK Cell Activity
Overview
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.
The following are additional, experimental immune disruptors. Researchers are investigating whether they can suppress NK cells in animals or test tubes.
Many of these studies had mixed results and human data are lacking.
Plus, some of these supplements have purported health benefits and can be safely used under medical guidance. Check with your doctor if you’re taking any of the supplements mentioned below.
Proposed NK Cell Inhibitors
- Lectins are hypothesized to initiate excess polyamine production, which may be the result of an effort to repair the damage to intestinal microvilli caused by lectins [68]. A high polyamine level may decrease NK cell populations [68].
- CRH/ACTH/Cortisol [69] – from stress or other causes
- Indoleamine 2,3-Dioxygenase (IDO) – activated by cortisol and inflammation [70]
- Somatostatin (Growth Hormone-Inhibiting Hormone) [71]
Lipoic Acid [72] and folic acid (synthetic form) may also inhibit NK cells, but they are also used as dietary supplements. Folic acid is a particularly important dietary addition for women in the first trimester as it prevents neural tube defects in the developing fetus [73].
Purported NK Cell Cytotoxicity Inhibitors
Estradiol is likely a natural NK cell inhibitor in women that can be problematic only if out of balance [74].
Testosterone and strength training may act in a similar way in men, and only abnormal testosterone levels warrant medical attention [36].
Acetylcholine [75] and fish oil/DHA are usually considered beneficial. Nonetheless, scientists are investigating whether they reduce NK cell cytotoxicity in test tubes. CBD is under investigation for the same reason [76, 77].
Lastly, the following addictive or Illegal substances also have an NK-cell-cytotoxicity-inhibiting effect and 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.
