Functional Medicine Research with Dr. Nikolas Hedberg, DC Dr. Nikolas Hedberg, DC - Functional Medicine Researcher

A new study entitled, “The Efficacy of Palmitoylethanolamide (Levagen+) on the Incidence and Symptoms of Upper Respiratory Tract Infection-A Double Blind, Randomised, Placebo-Controlled Trial” aimed to evaluate the effectiveness of a signaling lipid called Palmitoylethanolamide (PEA) in reducing the occurrence, duration, and severity of upper respiratory tract infections(URTIs).















The results showed that participants who took PEA experienced fewer URTI episodes and had reduced symptoms compared to those who took a placebo, suggesting that PEA may be a safe and effective treatment option for URTIs.







Palmitoylethanolamide (PEA) is a lipid compound that belongs to the N-acylethanolamine (NAE) family and has similar properties to endocannabinoids. In the context of cold and flu infections, PEA is suggested to regulate interleukins and inhibit mast cell production, thereby reducing inflammation.







PEA activates NF-κB pathways through peroxisome proliferator-activated receptors (PPAR), particularly PPAR-α, and concentration-dependent mechanisms to decrease NLRP3 and inflammasome activation, ultimately leading to a decrease in the expression of cytokines and alleviation of upper respiratory tract infection symptoms.







It is worth noting that the natural levels of PEA in the body and the use of PEA supplements have been found to be ineffective in producing significant clinical results due to poor absorption, resulting in low levels of PEA in the bloodstream. However, when PEA is combined with dispersion technology, such as Levagen+, the absorption of PEA is greatly improved, leading to higher concentrations in the bloodstream, which may enable a therapeutic effect.







This study was conducted over a period of 12 weeks. It was a double-blind, randomized, placebo-controlled trial, where participants were divided into two groups: an active group receiving 300 mg of Levagen+ PEA twice a day and a placebo group receiving maltodextrin. The purpose of the study was to investigate the efficacy of Levagen+ PEA compared to the placebo in terms of the incidence, severity, and duration of upper respiratory tract infections (URTI).  







During the study, 87 participants out of the total enrolled experienced at least one URTI, resulting in a total of 103 URTI episodes. The group receiving Levagen+ PEA reported significantly fewer URTI episodes (39) compared to the placebo group (64), and a lower number of participants who fell sick at least once during the study (32 vs. 55) when compared to the placebo group.







Participants in the Levagen+ PEA group reported a significantly lower severity score for scratchy throat and cough. Overall, compliance with the study was high for both groups in terms of capsule consumption.







The findings of the study indicate that individuals in the Levagen+ PEA group had a significantly lower number of upper respiratory tract infection (URTI) episodes compared to the placebo group.







The study suggests that Levagen+ PEA could be a viable treatment for preventing upper respiratory tract infections (URTIs) and alleviating symptoms of cold and flu. The findings indicate that Levagen+ PEA is safe and effective in reducing the frequency of URTI episodes and relieving scratchy throats and coughing in individuals with URTI symptoms.







I use PEA Luteolin Select from Moss Nutrition, which contains 300 mg of Levagen+ PEA and 50 mg of the flavonoid luteolin per capsule. PEA and luteolin have been shown to work synergistically in COVID-19-related illnesses such as Long COVID.







I have patients take 1 capsule twice a day with meals of PEA Luteolin Select during COVID-19, cold, and flu season for prevention and then increase to 2 capsu...

A new paper entitled “Isorhamnetin protects porcine oocytes from zearalenone-induced reproductive toxicity through the PI3K/Akt signaling pathway” investigated the effects of a natural flavonoid called isorhamnetin on the damage caused by a toxin called Zearalenone (ZEA) to pig oocytes (immature egg cells).















Zearalenone (ZEA) is a harmful mycotoxin found in moldy grain like corn, oats, and millet that can cause irreversible damage to the reproductive system of animals and humans. It can cause reproductive disorders by binding to estrogen receptors and has been shown to impair the development of sperm and oocytes in humans and animals.







ZEA can cause oxidative stress that leads to the production of reactive oxygen species (ROS), which can be harmful and contribute to cell death.







ZEA can also disrupt pregnancy, inhibit the meiosis of oocytes, and induce mitochondrial damage and stress in the maturation of oocytes. Since ZEA is heat-stable and cannot be completely eliminated from the food chain, it is important to explore potential compounds that can protect against ZEA-induced damage to oocytes.







In recent years, natural substances called flavonoids, which have antioxidant properties, have gained attention for their ability to support the development of oocytes. For example, quercetin has been found to increase the proportion of porcine oocytes developing into blastocysts, while kaempferol has shown potential in reducing the negative effects of aging on the development of porcine oocytes by improving mitochondrial function and reducing oxidative stress.







Isorhamnetin is a compound found in the herb ginkgo biloba and in foods like pears, onions, and peanuts. It has various pharmacological activities, such as being an antioxidant, anti-inflammatory, and antiviral.    







Isorhamnetin acts as an antioxidant by decreasing the production of reactive oxygen species (ROS) and increasing the expression of SOD2 protein, which helps protect against oxidative stress.







This study found that isorhamnetin can protect the oocytes from ZEA-induced damage by improving their development, reducing oxidative stress, preventing mitochondrial dysfunction, and inhibiting apoptosis.







This research provides a potential solution for reproductive toxicity caused by ZEA and treating female infertility.







Mold Toxicity and Ginkgo Biloba Clinical Applications







Ginkgo biloba is rich in isorhamnetin as well as other powerful flavonoids like quercetin, kaempferol, and luteolin which makes it the perfect herb for patients with mold toxicity.







Ginkgo biloba has many benefits including anti-inflammatory, antioxidant, antiviral, anticoagulant, anti-obesity, hypolipidemic, hypotensive, anti-diabetic, anti-cancer, adaptogenic, and it protects the brain, eye, inner ear, heart, liver, cardiovascular system, reproductive system, lungs, and kidneys.







Patients with mold toxicity tend to have reactivated herpes viruses like EBV, CMV, and HHV-6 and ginkgo biloba is effective against these types of viruses as explained in this article.







I use VascuSelect from Moss Nutrition which contains 120 mg of standardized ginkgo biloba extract along with grape seed extract and mango extract to further support microcirculation. 120 mg of ginkgo biloba twice a day is the usual dose for this versatile herbal medicine.







If you’re a practitioner who sees patients with mold toxicity and/or infertility, then VascuSelect should be considered an important part of your protocol.







Click here to learn more about the Hedberg Institute Membership to take your functional medicine practice ...

A new paper published in the journal Science entitled, “Persistent complement dysregulation with signs of thromboinflammation in active Long Covid” sheds light on the causes of Long COVID.







The authors begin by pointing out the current hypotheses about the causes of Long COVID, including persistent inflammation, autoimmunity, tissue damage, and viral reservoirs.























In this study, researchers followed 39 healthy individuals and 113 COVID-19 patients for up to a year to identify biomarkers associated with Long COVID. At the 6-month follow-up, 40 patients still experienced Long COVID symptoms. They collected blood samples and measured over 6500 proteins to identify potential biomarkers using computational tools and experimental evaluation.







In patients with Long COVID, there was an increased activation of the complement system, which is a part of the immune system that helps fight pathogens and damaged cells. This activation persists even after the acute phase of the disease. The complement system can cause damage to cell membranes, and in Long COVID patients, there is an imbalance in the formation of a complex called the terminal complement complex (TCC), also known as the membrane attack complex (MAC), which contributes to tissue damage.







Long COVID patients experienced increased markers of tissue injury in their blood, along with a thromboinflammatory signature. This means that there are signs of damage to tissues and an abnormal immune response involving the activation of endothelial cells and the breakdown of red blood cells. These findings suggest that Long COVID is associated with ongoing inflammation and potential blood clotting issues.







In patients with Long COVID, there are lower levels of antithrombin III, a protein that helps regulate blood clotting. This leads to increased cleavage by thrombin, which is a key factor in the formation of terminal complement complexes (TCCs).







Additionally, Long COVID patients show elevated markers of platelet activation and the presence of monocyte-platelet aggregates, particularly in cases where Long COVID symptoms persist for 12 months or more.







These patients also exhibit signs of antibody-mediated activation of the classical complement pathway, which is associated with increased levels of antibodies against cytomegalovirus (CMV) and Epstein-Barr virus (EBV).







In this study, the researchers also used a sensitive test to measure antinuclear antibodies (ANA) in patients with Long COVID. They found that patients with Long COVID had a higher prevalence of positive ANA results compared to those without Long COVID. Positive ANA tests can indicate autoimmunity.







Based on the data presented, it is suggested that Long COVID patients should undergo early cardiovascular assessment due to potential cardiovascular complications. Additionally, antiviral medications targeting SARS-CoV-2 or herpesviruses may help reduce inflammation and blood clotting in Long COVID patients. Therapies that target the terminal complement pathway could also be explored as potential treatment strategies for Long COVID and other post-infection syndromes.







Long COVID Clinical Applications







This paper confirms that inflammation of the blood vessels is common in Long COVID. Supporting microcirculation with herbs like ginkgo biloba, grape seed extract, and mango fruit powder can help reduce this inflammation and repair damaged blood vessels. These three herbs also are effective anti-viral agents against viruses like Epstein-Barr Virus (EBV) and Cytomegalovirus (CMV).







Ginkgo biloba has been shown to help improve the symptoms of Long COVID.

Ginkgo biloba, known for its distinctive fan-shaped leaves, has been used in traditional medicine for centuries, particularly in Asia. Ginkgo biloba is often touted as an herb for brain health, such as improving memory and cognition. This reputation does a great disservice to the most versatile herb in the world.







Ginkgo biloba can be used as a potent antiviral agent for a variety of viruses.















Ginkgo biloba has some key bioactive antiviral components:







Flavonoids and Terpenoids: Ginkgo leaves contain high levels of flavonoids and terpenoids, compounds known for their antioxidant properties. These substances contribute to the antiviral activity of the plant.







Ginkgolides and Bilobalides: These are unique terpene trilactones found in Ginkgo biloba, which have specific antiviral activities.







Ginkgo Biloba’s Mechanisms of Antiviral Action







The antiviral properties of Ginkgo biloba are multi-faceted, involving multiple mechanisms:







Inhibition of the fusions and synthesis of proteins in the viruses herpes simplex 1 and 2 (HSV-1 and HSV-2).







Inhibition of genome replication in cytomegalovirus (HCMV) and Zika virus (ZIKV).







Inhibition of viral fusion proteins in HIV, Ebola virus (EBOV), influenza A virus (IAV), and Epstein-Barr virus (EBV).







Inhibition of the targeting protein and DNA of coronoviruses (SARS-CoV-2), varicella zoster virus (VZV), and measles virus.







Inhibition of Viral Entry and Replication: Some studies suggest that Ginkgo biloba extracts can interfere with the ability of viruses to enter host cells or replicate. This is a key step in preventing the spread of viral infections.







Immune System Modulation: Ginkgo biloba might enhance the body's immune response against viral infections. By modulating immune functions, it could help in controlling viral spread and severity.







Anti-inflammatory Effects: The anti-inflammatory properties of Ginkgo biloba can be beneficial in reducing the severity of symptoms associated with viral infections.







Research on Ginkgo Biloba’s Antiviral Properties







Anti-MERS-CoV and Anti-HCoV-229E Properties: A study focused on the antiviral activities of Ginkgo biloba leaf extracts against Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and Human Coronavirus 229E (HCoV-229E).







Inhibition of Enveloped Viruses: Research published in Scientific Reports discussed how ginkgolic acid, a component of Ginkgo biloba, inhibits the fusion of enveloped viruses.







The study found that ginkgolic acid had a strong inhibitory effect on Human Cytomegalovirus (HCMV) and also tested its effects on Herpes Simplex Virus-1 (HSV-1) and Zika Virus (ZIKV).







Researchers also found broad spectrum inhibition by ginkgolic acid of all three classes of fusion proteins including HIV, Ebola virus (EBOV), influenza A virus (IAV) and Epstein Barr virus (EBV).







In addition, inhibition was found of a non-enveloped adenovirus.







The authors conclude that ginkolic acids may potentially be used to treat acute infections (e.g. Coronavirus, EBOV, ZIKV, IAV and measles), and also topically for the successful treatment of active lesions (e.g. HSV-1, HSV-2 and varicella-zoster virus (VZV)). It was observed that ginkgolic acid could inhibit the entry of these viruses into cells, thereby blocking viral replication.







Another study entitled, “Ginkgolic acids inhibit SARS-CoV-2 and its variants by blocking the spike protein/ACE2 interplay” found that ginkgolic acids from ginkg...

For people with food sensitivities and chronic digestive disorders, the holiday season can be tough. Invitations to indulge in forbidden foods are everywhere—from checkout lines and television ads to office parties and family gatherings. For many, resisting temptation may be an insurmountable challenge.















Sometimes, the visceral presence or memory of how a particular savory dish or sweet treat made one feel in the past is enough to cause one to forget (or simply not care) how that food will make one feel in the present. Which is to say: lousy. Bloated, flatulent, running to the toilet, or in pain. The aftermath of a holiday feast can leave anybody feeling a little sluggish the next day, but those with a medical reason to avoid certain foods might need extra support to recover.







A “3-Day Gut Reset” incorporating a full elemental diet is probably the quickest way to restore digestive function and comfort following such dietary indiscretions. This brief, modified, protein-sparing fast is easy to implement with a product such as Elemental Select™, Moss Nutrition’s tasty, vanilla flavored meal replacement powder.







Elemental Select™ contains all the essential vitamins, minerals, and macronutrients needed for proper physiologic function, in their “elemental” predigested forms. When mixed with water, this complete, easy-to-absorb nutritional shake can be consumed throughout the day without putting any strain on the digestive organs, enabling rapid intestinal healing and repair over the brief course of a three-day period.







Both full and partial elemental diets are recognized as important management strategies for people with digestive disorders. A full elemental diet, for example, was recently shown to prevent surgical recurrence of severe inflammatory bowel disease at a dose of 1200 calories per day. Decreasing intestinal inflammation, reversing leaky gut syndrome and intestinal permeability, rebalancing the microbiome, and improving digestive health are among the clinically researched benefits of elemental diet therapies.







Typically, elemental diets are employed over a period of two to six weeks. But shorter, intensive applications can help with rapid recovery from a relapse, such as may occur when patients with compromised digestion indulge in a holiday spree. A few days of full elemental diet protocol can make a significant difference in helping these folks get back on track and quickly feel their best.







One 30-serving container of Elemental Select™ is sufficient to complete an entire 3-Day Gut Reset. The patient simply consumes ten scoops of the product per day, and nothing else. (Each scoop contains 150 calories of bioavailable nutrition; therefore, ten scoops provide 1500 calories, enough energy for most people to function normally.) The ten daily scoops may be divided in various ways, depending entirely on individual patient preferences. The most popular method is as follows: In a blender, combine two scoops of Elemental Select™ with 8 to 10 ounces of water. Consume five times per day, at regular intervals. 







While two scoops, five times a day is ideal for most people doing a 3-Day Gut Reset, some may prefer to mix a single scoop in 8 ounces of water, and repeat ten times per day, generally on the hour. Others may opt to divide their daily ten scoops into three or four equal servings, and replicate a “breakfast, lunch, and dinner” routine, with optional snack. (In this latter case, at least 16 ounces of water should be used to blend each “meal,” since several scoops of powder will be taken at once.) All these dosing options are absolutely fine.







Whatever schedule is chosen, it is critical to remember that Elemental Select™ is an extremely nutrient dense formula.

Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC) or long-haul COVID, refers to a condition where individuals experience persistent symptoms or develop new symptoms after recovering from the acute phase of COVID-19. Long COVID can affect individuals who had mild, moderate, or severe initial COVID-19 infections and can persist for weeks or months after the initial illness.







The specific symptoms and their duration can vary widely between individuals, but common symptoms of long COVID include fatigue, shortness of breath, cough, joint pain, chest pain, muscle weakness, brain fog, difficulty concentrating, memory problems, sleep issues, depression, anxiety, and other neurological or psychiatric symptoms. It can also affect multiple organs in the body, such as the heart, lungs, kidneys, and brain.























How does COVID-19 affect microcirculation?







Microcirculation refers to the circulation of blood in the smallest blood vessels, including arterioles, capillaries, and venules. While COVID-19 primarily affects the respiratory system, there is evidence suggesting that it can have systemic effects, including impacts on the cardiovascular system and microcirculation.







Here are some potential ways in which COVID-19 may affect microcirculation:







Endothelial Dysfunction:







COVID-19 has been associated with endothelial dysfunction, which is a condition where the cells lining blood vessels (endothelial cells) do not function properly. Endothelial dysfunction can lead to impaired regulation of blood flow and increased permeability of blood vessels.







In severe cases, viral infection and the resulting immune response may damage endothelial cells, contributing to a pro-inflammatory state and a potential disruption of microcirculation.







Blood Clotting and Thrombosis:







COVID-19 is known to be associated with an increased risk of blood clot formation (thrombosis). The formation of blood clots can potentially affect microcirculation by blocking small blood vessels.







The hypercoagulable state observed in some COVID-19 patients may contribute to microvascular thrombosis, leading to impaired blood flow in affected tissues.







Inflammatory Response:







The body's inflammatory response to the virus can also impact microcirculation. Inflammation can lead to the release of inflammatory mediators, causing vasodilation (widening of blood vessels) and increased permeability, which may affect blood flow in the microcirculation.







Hypoxia and Tissue Damage:







Severe cases of COVID-19 may lead to respiratory distress and hypoxia (low oxygen levels). Hypoxia can have detrimental effects on tissues and organs, potentially impacting microcirculation.







Tissue damage and inflammation in the lungs may trigger a systemic response that affects microvascular function in other organs.







Impaired Oxygen Delivery:







In severe cases of COVID-19, where acute respiratory distress syndrome (ARDS) develops, oxygen exchange in the lungs becomes compromised. This can lead to inadequate oxygen delivery to tissues and affect microcirculation.







What is grapeseed extract?







Grapeseed extract is a dietary supplement derived from the seeds of grapes. It is rich in antioxidants, particularly compounds known as oligomeric proanthocyanidin complexes (OPCs). Additionally, grape seed extract contains flavonoids, another class of polyphenols with antioxidant properties.