Many Gulf War veterans have suffered from multiple symptoms and illnesses for the past 30 years. Isn't it time to really look at what natural medicine can do to help?

Dr. Gary Null reported insufficient research into options for veterans and lack of understanding of Gulf War syndrome (GWS).^[i],[ii] The Veterans' Administration will not acknowledge GWS but calls it "chronic multisymptom iIllness" (CMI) with four illness areas:

1. Chronic fatigue syndrome
2. Fibromyalgia
3. Gastrointestinal disorders
4. Undiagnosed illnesses -- headaches, fatigue, muscle and joint pain, respiratory disorders and neurological problems^[iii]

As many as 300,000 veterans or 44% of those engaged in the Gulf War self-reported having Gulf War Illness (GWI) or what is called GWS.^[iv] Although they served from 1990 to 1991, Gulf War veterans deployed are three times more likely to report GWS symptoms of irritability, feeling detached, muscle weakness, diarrhea and rash than veterans from the same era but in different locations.^[v]

In a comparative study of 962 participants from eight different diseases, including GWS, schizophrenia, Alzheimer's disease, posttraumatic stress disorder (PTSD), major depressive disorder, relapsing-remitting multiple sclerosis (RRMS), Sjögren's syndrome (SS) and rheumatoid arthritis (RA) and a healthy control group, GWS was most similar to three immune-related diseases -- RRMS, SS and RA. GWS impacts immune-related processes by altering brain communications.^[vi]

The variety of GWS symptoms -- pain, fatigue, cognitive dysfunction, gastrointestinal issues, respiratory difficulties and dermatological complaints -- point to GWS being a neuroimmune condition involving systemic inflammation.^[vii]

Researchers have shown an association between neurotoxicant exposures to GWS veterans and increased odds of cognitive/mood, fatigue and neurological symptoms, and it worsens over time.^[viii],[ix]

Seven Natural Options for Gulf War Syndrome

This review highlights research on the most effective natural options such as curcumin, nettle, pine bark, resveratrol, genistein, CoQ10 and probiotics to address the array of symptoms and illnesses associated with GWS.

1. Curcumin

Curcumin has helped with multiple symptoms in GWS -- inflammation, depression, memory, anxiety, gastrointestinal diseases and pain -- due to its anti-inflammatory and analgesic properties.

In a clinical trial of 20 men with GWS, three botanical agents with anti-inflammatory actions --– curcumin, boswellia and pine bark extract -- were tested against a placebo. Participants had 30 days each of placebo, lower-dose botanical and higher-dose botanical. Participants then repeated the process with a new botanical until completing all three botanical cycles. 

Curcumin reduced GWS symptom severity significantly more than placebo at both the lower and higher dosages and pine bark was also more effective than the placebo but only at the higher dosage.^[x] In an animal model of GWS, scientists exposed 43 rats to low doses of GWS-related chemicals and mild stress daily for 28 days followed by either curcumin or control treatment daily for 30 days.

Curcumin helped maintain better hippocampal function -- better memory function and reduced anxiety-like behavior. Several cellular and molecular changes -- increased neurogenesis and diminished numbers of activated microglia in the hippocampus -- appeared to underlie its benefits.^[xi]

A meta-analysis of 32 trials including 2,038 participants showed the anti-inflammatory effects of curcumin -- reductions in C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF α), IL-8 and monocyte chemo attractant protein-1 (MCP1) and increases in IL-10.^[xii]

A group of 108 males between 31 and 59 years old were divided into a treatment group -- two capsules of 1,000 milligrams (mg) of curcumin -- or placebo group -- two capsules of soybean powder daily for six weeks -- along with current medicines. Curcumin significantly reduced antidepressant behavior, inflammatory cytokines and cortisol concentrations and increased plasma brain-derived neurotrophic factor levels compared to the placebo.^[xiii]

GWS complaints include abdominal pain and discomfort, diarrhea and dyspepsia (indigestion) and are frequently diagnosed as functional gastrointestinal disorders such as irritable bowel syndrome (IBS), functional dyspepsia and functional abdominal pain syndrome.^[xiv]  Some natural options to treat GWS include curcumin, fennel and resveratrol.

Inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, are life-long, chronic and relapsing problems. In a systematic review of 30 studies, several treatments -- fiber, polyphenols, fatty acids and diet -- for those patients with Crohn's disease and ulcerative colitis can improve quality of life and invoke clinical remission. Two polyphenols -- curcumin and resveratrol -- have effectively decreased gastrointestinal disease activity.^[xv]

The anti-inflammatory property of curcumin and the antispasmodic (spasm relief) and carminative (gas relief) effects of fennel suggest their combined use to treat functional bowel disorders. In a study of 121 patients with mild-to-moderate IBS symptoms, patients were randomly assigned to 42 mg of curcumin with 25 mg of fennel essential oil treatment or placebo given in two capsules for 30 days.

Results showed significant decreases in IBS symptom severity and abdominal pain and improved quality of life within 30 days of treatment. The percentage of symptom-free patients was 26% in the curcumin-fennel group compared to 7% in the placebo group.^[xvi]

2. Nettle

Extracts of nettle leaf are successfully used as anti-inflammatory remedies for rheumatoid arthritis.^[xvii] In the second part of the study of 29 men suffering from GWS, three botanicals -- stinging nettle, reishi mushrooms and epimedium -- were used at a low dose, high dose and a placebo for 30 days each, until each participant completed all three botanical trials. Only the higher dose of stinging nettle was able to decrease GWS symptom severity for veterans.^[xviii]

3. Pine Bark or Pycnogenol

Pycnogenol is an extract from the bark of the French maritime pine with strong antioxidant and anti-inflammatory abilities. Five trials including 324 participants were reviewed in a meta-analysis showing that more than 150 mg per day of pine bark decreased the inflammatory marker CRP.^[xix]

In an animal model of induced allergic rhinitis or hay fever, rats given pycnogenol had increased IL-10 anti-inflammatory effects and decreased mucosal edema and inflammatory markers TNF-α and the IL-1β, which helped to suppress overall allergic response.^[xx]

Overactivation of microglia produces proinflammatory agents implicated in various GWS brain and neurological issues. In a brain-disease-induced mice study, pycnogenol treatment significantly lowered the inflammatory markers nitric oxide (NO), TNF-α, IL-6 and IL-1β.

Pycnogenol exerted anti-inflammatory effects through pathways inhibiting the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) -- a controller of cytokine production -- and activating protein 1 (AP-1), a regulator of cell proliferation and survival.^[xxi]

4. Resveratrol

Resveratrol is a natural compound found in foods and red wine that has shown positive anti-inflammatory effects for intestinal inflammation and RA. In a meta-analysis of 18 studies involving 544 animals, resveratrol successfully reduced pain, swelling, cartilage loss and arthritic symptoms.

RA is accompanied by increased oxidative stress due to a high malondialdehyde (MDA) level and low superoxide dismutase (SOD) activity. Resveratrol reduced MDA level and increased SOD activity. Experimental RA models also showed a decrease in pro-inflammatory cytokines TNF - α, IL - 6 and IL-1 and increased IL-10, which would help with RA symptoms.^[xxii]

Skin rashes and diseases also plague service people with GWS and resveratrol has been shown to be effective in animal and in vitro studies to alleviate inflammatory and autoimmune skin diseases^[xxiii] like atopic dermatitis,^[xxiv] psoriasis,^[xxv] skin cancers^[xxvi] and skin fibrosis.^[xxvii]

Resveratrol and curcumin both have significant anti-inflammatory, bacteria-regulating and immune-promoting effects. A combination of curcumin and resveratrol was given in an animal model and inhibited the release of critical inflammation molecules -- IL-1β and TNF-α -- and increased the secretion of immunoglobulin.

This combined treatment effectively regulated animal gut microbiota, down-regulated the toll-like receptor 4 (TLR4) signaling pathway, which triggers the immune response, alleviated intestinal inflammation and ultimately increased intestinal immune function.^[xxviii] Resveratrol, curcumin and Simvastatin -- a statin drug -- have been demonstrated efficacious in various experimental animal inflammation models.

In a mice model induced with acute intestinal inflammation, resveratrol treatment resulted in the best long-term survival. All three treatments down-regulated immune responses and maintained gut barrier function. These findings show new natural options with similar or better results than a statin drug that can treat inflammatory bowel diseases common in GWS veterans.^[xxix]

Microglia are the primary cells that exert immune function in the central nervous system and can initiate neurodegenerative diseases. Through in vitro and mouse study of induced neuroinflammatory injury, resveratrol reduced inflammatory damage and promoted microglia polarization, suppressing brain inflammation.^[xxx]

Chronic airway inflammation and issues are characteristics of chronic obstructive pulmonary disease (COPD), which also afflicts many GWS patients. Lymphocytes were isolated from the blood of 34 COPD and 30 healthy subjects, then randomly given a placebo, dexamethasone or DEX (0.5 micromole per liter – µmol/l) -- a steroid drug, resveratrol (12.5 µmol/l) or genistein (25 µmol/l).

The percentage of NF-κB-positive cells and the levels of TNF-α and MMP-9 in lymphocytes from COPD patients was significantly higher than in healthy subjects. All three factors were significantly reduced in lymphocytes treated with DEX, resveratrol and genistein but the inhibitory effects of resveratrol on NF-κB, TNF-α and MMP-9 were more potent than those of genistein and potentially safer than chronic use of steroids.^[xxxi]

5. Genistein

Two isoflavones, genistein -- found in legumes -- and puerarin -- from the kudzu plant -- inhibit oxidative stress and protect the brain.^[xxxii] Oxidative stress plays an essential role in chronic inflammatory diseases in the airway and the brain, indicating that antioxidants like genistein and puerarin may help to control these common GWS illnesses.

In a nutrition study of 1,033 asthma patients, aged 12 to 75, genistein produced better lung function in asthma patients than other nutritional supplements like puerarin.^[xxxiii]

Scientists tested the blood of 32 asthma and 31 healthy subjects and randomly divided them into four treatments -- control, DEX, genistein and puerarin groups. The percentage of NF-kappa B cells and the level of TNF-alpha were significantly higher in asthma patients at 23% compared to 7.2% for healthy people.

Genistein lowered NF-kappa B positive cells to 15.2% while puerarin decreased it to 16.2% compared to 23.1% in control asthma patients. Similarly, TNF showed the biggest decrease in the genistein group followed with slightly less potent results with puerarin, but both antioxidants were significantly better than the control groups in asthma patients.^[xxxiv]

Three of the most common problems of GWS are sleep disorders, fatigue and cognitive trouble.^[xxxv] Sleep deprivation is the main factor in cognitive dysfunction and elevation in oxidative stress and inflammation in the body, including the brain.

In a mouse model of sleep deprivation, genistein at 10 mg, 20 mg and 40 mg per kilogram was administered for 25 days. Dose-dependent genistein overcame cognitive deficits, elevated total antioxidant capacity, SOD and glutathione levels and lowered MDA in the cortex and hippocampus.

Genistein treatment also significantly suppressed oxidative stress markers of NF-κB p65, nitrate oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) activated in the cortex and hippocampus, as well as inhibited the release of pro-inflammatory cytokines TNF-α, IL-6 and IL-1β.^[xxxvi]

6. Coenzyme Q10 or Ubiquinol

Coenzyme Q10 (CoQ10) -- known as ubiquinol in its reduced form --  acts as an antioxidant to protect cells from oxidative stress damage. The chemical and toxic exposures veterans in the Gulf War encountered are known to inhibit acetylcholinesterase (AChE) activity, resulting in the accumulation of neurotransmitters in neuromuscular junctions and synaptic gaps, which can ultimately result in mitochondrial dysfunction.^[xxxvii]

GWS has symptoms similar to patients with certain mitochondrial disorders. In a study of 21 cases of GWS and seven controls, veterans with GWS were found to exhibit greater mitochondrial DNA damage than controls, consistent with mitochondrial dysfunction.^[xxxviii] In a trial of 46 veterans with GWS, compared to a placebo, 100 mg per day of CoQ10 significantly improved physical function and GWS symptoms.^[xxxix]

CoQ10 is a potent free radical scavenger, adenosine triphosphate (ATP) -- the cells' energy source^[xl] -- production enhancer, anti-inflammatory and neuroprotective, so it is not surprising that CoQ10 levels are low and supplementation with 150 mg or 200 mg (during high stress times) of ubiquinol can help to improve symptoms in two GWS illness areas -- fibromyalgia and chronic fatigue syndrome.^[xli],[xlii]

In a study of 130 adults with three or more migraine headache episodes per month, those who took a dietary supplement with CoQ10, riboflavin and magnesium versus a placebo for three months reduced the number of days the headache persisted and their pain and rated their overall relief higher.^[xliii]

7. Probiotics

Many diseases like obesity, liver disease and IBS are being cured or decreased by probiotics and new studies where GWS patients take probiotics for longer periods of time are predicted to improve symptoms connected with GWS.^[xliv]

In a mouse study, exposures to suspected GWS agents -- toxins and chemicals -- were confirmed as factors that increased intestinal inflammation and neuroinflammation as well.^[xlv] In a meta-analysis of 42 clinical trials with 1,138 participants in intervention and 1,120 in control, probiotic supplements significantly reduced pro-inflammatory cytokines, including hs-CRP, TNF-a, IL-6, IL-12 and IL-4, and increased IL-10, an anti-inflammatory cytokine.^[xlvi]

In a systematic review of the literature on probiotics and their role in countering inflammation and allergy conditions, more and more probiotic bacterial strains are being proven for their ability to address immune function, atopic and inflammatory conditions.^[xlvii]

Diet, gut microbiota and their metabolites -- short-chain fatty acids -- impact several inflammatory and autoimmune diseases, like asthma, arthritis, fibromyalgia and IBS. Use of diet and probiotics can prevent and treat these diseases.^[xlviii]

Natural Medicine's Role in Gulf War Syndrome Relief

Thirty years after the Gulf War, veterans are still searching for ways to alleviate GWS illnesses and symptoms and natural medicine may give them answers. Please see GreenMedInfo.com's research on Gulf War Syndrome and the natural options of curcumin, pine bark, resveratrol, nettle, genistein, CoQ10 (ubiquinol) and probiotics.

References

[i] Null, G., GreenMedInfo, Blog Entry, Gulf War Syndrome Killing Our Own, Part 1, /blog/gulf-war-syndrome-killing-our-own-part-1