The purpose of this research study is to determine how pycnogenol may reduce Gulf War Illness (GWI) symptom severity. The study will also examine the safety of this treatment and determine the optimal dosage. The investigators believe that GWI involves inflammation in the body and brain that causes fatigue, pain, cognitive disruption, and other symptoms. Botanicals that reduce inflammation may help treat GWI.

This study uses a decentralized design where individuals can participate from anywhere in the Alabama. Botanicals will be received by mail. Participants will also receive placebo (capsules with an inactive substance) during the treatment phase of the study. All participants will have been present in the Persian Gulf between 1990 and August 1991. This study will be tested on GWI participants recruited in Alabama, with a total of up to 20 participants enrolled (to account for potential withdrawals to obtain 10 completed participants) for the entire study. Participation will last 12 months.

The first stage of the study is the baseline phase. During this time, participants will complete weekly questionnaires about symptom severity ratings but will not take any capsules. The baseline stage will last for 30 days.

After the 30-day baseline, the treatment stage will begin. Capsules will be taken once in the morning, and once before bed. This study is single-blind, meaning that participants will not know when placebo or pycnogenol are received. There are also four possible dosages for pycnogenol.

The capsules will be packaged to indicate the order in which they should be taken. The capsules will be packaged in blister packs and shipped to participants. The capsules are designed to look the same throughout the study, though the contents can change. This treatment stage is the longest, lasting 10 months.

During the treatment stage, participants will also be asked to complete weekly questionnaires about GWI symptoms. These weekly questionnaires will also ask about changes in symptoms and overall quality of life, as well as changes in physical and mental health. Questionnaires can be completed on a smartphone, computer, or tablet. If participants do not have an appropriate device, or do not want to use a personal device, a tablet can be sent for the study. A research team member will speak with participants to set up electronic device connections and will verify the information is received.

At the end of the treatment stage, participants will stop taking capsules and will complete the end line stage. This stage is the same as the baseline stage in which participants will complete weekly symptom measures without taking capsules. This stage will last for 30 days.

After completion of the study, participants will be told when placebo was received, and what dosage(s) of treatment were received. Participants will also be shown how GWI severity changes over time.

While this study is long, it is designed to not be a significant burden to daily life. On most days, participation (taking morning capsules, taking evening capsules, and completing weekly symptom severity reports) should take approximately 2 minutes.

Inclusion Criteria:

• Meet the Kansas GWI case definition
• Meet the CDC GWI case definition
• Able to commit to a 12-month study
• Male
• Participants will be individuals in our Gulf War database who have already completed our other botanical trial, Curcumin, Resveratrol, and Stinging Nettle as Treatments for Gulf War Illness (NCT05377242).

Exclusion Criteria:

• Currently involved in another experimental treatment study
• Female
• Have a blood clotting disorder
• Reported diagnosis of diabetes with a A1C greater than 9
• Use of contraindicated medications (see below):
• Anticoagulants (such as warfarin, heparin, etc.)
• Lithium
• Tacrolimus (Prograf)
• Cancer medications (Alkylating agents, antitumor antibiotics, Topoisomerase I inhibitors, Tamoxifen)
• Daily Use of Antiplatelet agents (e.g. aspirin, clopidogrel)
• Nitroglycerin
• Hypotension
• Need for surgery during study period.

This study is single-blind, participants will not know when they received placebo or pycnogenol. There are also four possible dosages for pycnogenol. Participants will also receive placebo (capsules with an inactive substance) at some point during the treatment phase of the study.