COVID-19 and Lab Tests

Coronaviruses are well-known triggers of respiratory infections. However, COVID-19 has emerged only recently and we are still in the early stages of learning about its effects on the human body.

One of the most important questions in this pandemic is what makes certain people fare better and others worse once they get infected?

Research has shown that the following factors are associated with higher COVID-19 hospitalization and mortality [R, R, R, R, R, R, R, R, R]:

• Severe obesity (BMI>35 kg/m2)
• Older age
• Being male
• Smoking
• High blood pressure (hypertension)
• Diabetes
• Heart disease
• Lung disease

Obviously, the only way to know for sure whether or not you have COVID-19 is to do an actual COVID-19 test. But there are other lab tests that may help doctors decide who needs testing when there are not enough tests for everyone. Also, doctors and scientists are looking onto lab tests that could help them predict a person’s risk of hospitalization and severe complications. We’ve summarized them below.

Limitations

In this post, we will go over the different labs that have been used to predict COVID-19 diagnosis and outcomes. However, as we talk about these labs and their link to COVID-19, keep in mind that:

• What we know is often based on a few small studies, which means that there is not enough research and that the studies are of limited quality.
• Many of the lab tests, with the exception of metabolic markers and vitamin D, are useful in hospital settings but are of little practical value to you at home when you are not infected.
• Correlation does not equal causation. This means that although there may be a link between a certain lab test and COVID-19 outcomes, that does not mean that the labs themselves are causing the outcome.

Therefore, take the following information with a grain of salt, because what we know will likely change as new information becomes available. We’ll keep you updated on all new significant findings.

Metabolic Markers

First, let’s discuss metabolic markers which are routinely used to estimate one’s overall metabolic health. If you are not already keeping track of these, now is

The post 14 Labs That Predict COVID-19 Diagnosis and Outcomes appeared first on SelfHacked.

1) White Blood Cells (Leukocytes)

When we are talking about immunity and immune system health, there’s no better place to start than white blood cells (WBC) or leukocytes. These cells protect us against infections and diseases by fighting bacteria, viruses, and other foreign invaders. That is why, when you are checking the health of your immune system, the first step should be to get a complete blood count (CBC) with a WBC differential (or alternatively just a WBC differential).

CBC gives you information about your blood cells: red blood cells (RBCs), white blood cells (WBCs), and platelets. It’s a common test that is normally a part of a routine health exam. Doctors use it to help detect a wide range of health issues, including anemia, infections, clotting problems, immune system disorders, and blood cancers [R, R].

When it comes to white blood cells, having low WBC levels, for example, can mean that your body doesn’t have adequate resources to fight against infections properly. High WBC, one the other hand, may mean that you’re currently fighting an infection or that there’s inflammation in the body.

White Blood Cell Differential

If your white blood cells are decreased or increased, it is important to check which particular cells are the cause. WBC differential means that, apart from giving a total white blood cells count, the test will also include the counts and/or percentages of the 5 major types of white blood cells:

• Neutrophils — these first-responders at infection and inflammation sites help fight infection by ingesting microbes and releasing enzymes that kill them [R, R]
• Lymphocytes — these are cells that produce antibodies against microbes, kill cancer or virus-infected cells, and help direct the immune response [R, R, R, R]
• Monocytes — cells that kill microbes, ingest foreign particles, remove dead cells, and boost the immune response [R, R, R].
• Eosinophils — cells that fight parasite infections and are involved in the allergic response [R]
• Basophils — cells involved in inflammatory responses [R, R, R].

Having a normal

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Vitamin C Deficiency

Symptoms

Early indications of Vitamin C deficiency are fatigue, malaise, depression, and they may manifest as a reduced desire to be physically active [R].

Scurvy (pathological Vitamin C deficiency) leads to blood vessel fragility resulting in hemorrhage, as well as connective tissue damage due to failure in collagen production, often leading to loss of teeth and tendon rupture. At worse, scurvy can lead to death [R, R].

Other signs and symptoms of severe vitamin C deficiency include [R]:

• Poor wound healing
• Fatigue
• Weight loss
• Gum inflammation and bleeding
• Petechiae (tiny purple, red, or brown spots on the skin), ecchymosis (a type of bruise), and purpura (purple-colored spots on the skin)
• Joint pain
• Dry eyes and dry mouth
• Corkscrew hair

Clinical scurvy can be avoided by intaking as little as 10 mg of Vitamin C per day. Scurvy is extremely rare in developed countries [R].

However, mild Vitamin C depletion has been observed in 10-30 % of the presumed healthy population [R, R].

Causes

Causes shown here are commonly associated with vitamin C deficiency. Work with your doctor or other health care professional for an accurate diagnosis.

One of the major causes of low vitamin C levels is eating a poor diet lacking in fresh fruits and vegetables. This is commonly seen in:

• Low-income individuals [R]
• Elderly individuals who eat a tea-and-toast diet [R]
• Alcoholics and drug users [R]
• People who follow fad diets [R]
• Anorexics [R]
• People with mental illness [R]

People with malabsorption issues caused by certain gut conditions (i.e., Crohn’s disease, celiac disease) are also at risk for vitamin C deficiency [R].

Low vitamin C levels can also be caused by:

• Heavy metal toxicity [R]
• Viral illnesses [R]
• Overactive thyroid gland (hyperthyroidism) [R]
• Kidney disease/failure [R]
• Cancer [R]

Certain drugs can lower vitamin C levels:

The post 29+ Foods High in Vitamin C & Deficiency Symptoms appeared first on SelfHacked.

Disclaimer: Levodopa is prescribed, usually in combination with carbidopa, to treat Parkinson’s disease. This post provides a summary of the information on its side effects available in the scientific and clinical literature. Please discuss your medications, dietary supplements, and any potential side effects you are experiencing with your healthcare provider.

L-DOPA & Sinemet Safety Overview

L-DOPA has been the prime treatment for Parkinson’s disease since the 1960s. It increases dopamine levels in the brain, which provides relief of Parkinson’s symptoms [R].

L-DOPA is administered with carbidopa (also known as SINEMET) for the treatment of Parkinson’s disease. The combination is classified by the FDA as a drug and is available only with a doctor’s prescription.

L-DOPA 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. Speak with your doctor before supplementing.

In this article, we’ll go over:

• Typical and rare side effects of L-DOPA and SINEMET (carbidopa levodopa)
• Mixed effects of L-DOPA reported in the scientific literature
• Potential long-term side effects of L-DOPA and SINEMET (carbidopa levodopa)

Side Effects of L-DOPA, Sinemet & Levodopa-Carbidopa Combinations

Summary

The significant body of research on treatments shows that levodopa is generally safe and well-tolerated. Relevant side effects that have been reported with L-DOPA, Sinemet, and various levodopa-carbidopa combinations include the following:

• Agitation [R]
• Fatigue [R]
• Anxiety [R]
• Hallucinations [R]
• Dizziness [R]
• Confusion [R]
• Nausea [R]
• Vomiting [R]
• Coughing [R]
• Hypotension (low blood pressure) [R]
• Gut bleeding [R]
• Arrhythmias [R]
• Insomnia [R]
• Vivid dreams [R]
• Somnolence (sleepiness, drowsiness) [R]
• Hair loss [R]
• Excessive libido [R]
• Swelling [R]

Rare Side Effects

Life-threatening side effects like Neuroleptic Malignant Syndrome (NMS) are rare but possible [R

The post L-DOPA & Sinemet (Carbidopa-Levodopa) Side Effects appeared first on SelfHacked.

What Is Leaky Gut?

The theory is fairly simple. When there are abnormalities in the intestinal barrier, the intestinal permeability increases. This potentially means that more of the gut content can pass/leak through, which is referred to as “leaky gut” [R].

Some scientists think that when the gut is leaky, gut bacteria and their products may escape the gut, which could potentially produce inflammation and cause tissue damage. Similarly, food-derived antigens (proteins or partially digested proteins) could pass through the gut and promote both local or whole-body immune responses [R].

To learn more about what makes the gut “leaky” and the conditions associated with it, check out this post.

How to Prevent a Leaky Gut

As leaky gut may occur as a symptom in a number of underlying diseases, the most important thing is to work with your doctor to address any potential underlying health condition.

For example, several studies have shown that chronic infections can increase gut permeability, and therefore they need to be addressed if possible [R, R, R, R, R].

Some clinical studies show that addressing leaky gut may be beneficial in some gut-related conditions such as inflammatory bowel disease (IBD), diarrhea, irritable bowel syndrome (IBS), and celiac disease. However, at this point in time, there is little to no clinical evidence that addressing leaky gut could improve any particular non-gut related condition.

1) Potentially Beneficial Lifestyle and Dietary Changes

Much of the emerging research shows that stress may increase intestinal permeability [R, R, R]. Managing stress levels is one way to potentially improve the function of your intestinal barrier and your overall health.

A healthy circadian rhythm may also help keep your gut healthy [R].

Alcohol increases intestinal permeability and is best avoided if you have gut issues [R, R, R]. Even moderate consumption can increase intestinal permeability in people who have gut inflammation [R].

If you have certain food sensitivities (e.g. gluten), you may need to avoid offending foods. However, make sure your diet is overall healthy and well balanced, to avoid nutritional deficiencies [R].

2) Moderate Exercise

In 30 people with diabetes who initially had

The post Improving Leaky Gut: Diet, Supplements & How to Heal appeared first on SelfHacked.

What Is Ferritin?

Ferritin is a protein complex that stores iron in a soluble, non-toxic form, and transports it to areas where it is required [R].

Iron has many important roles in our bodies: it helps make red blood cells and is needed for muscle and heart cells to produce energy. But iron can also be toxic to cells because of its capacity to generate reactive species, which can damage DNA and proteins. Ferritin captures and buffers the iron within cells and is very important for good health [R].

Low ferritin levels signal that the body’s iron stores are low. Higher levels, on the other hand, may indicate that you have a condition that causes the body to store too much iron [R]. 

High Ferritin Levels

Interpretation

If ferritin is high, there is iron in excess or else there is an acute inflammatory reaction in which ferritin is mobilized without iron excess.

Ferritin is increased under oxidative stress. It is increased by the antioxidant-responsive element (ARE) [R].

Ferritin, in turn, can increase the liver proinflammatory mediators IL-1b, iNOS, RANTES, IkappaBα, and ICAM1 [R].

Ferritin is used as an indicator of iron overload disorders, such as hemochromatosis or hemosiderosis.

As ferritin is also an acute-phase reactant (a part of the body’s response to inflammation), it is often elevated in various diseases. A normal C-reactive protein (CRP) can be used to exclude elevated ferritin caused by acute phase reactions.

Ferritin levels of greater than 1,000 ng/ml are a nonspecific marker of illness, including infections and cancer [R].

However, ferritin over 300 can indicate some inflammation.

Diseases Associated with Higher Ferritin

At a Glance

The most common causes of elevated ferritin levels are obesity, inflammation, and daily alcohol intake.  The most common cause of genetic-related elevated ferritin levels is the condition hemochromatosis. Additional causes include diabetes and metabolic syndrome [R, R].

We have an in-depth post dedicated to diseases associated with conditions that have higher or lower ferritin.

Circulating ferritin is widely recognized as an acute phase reactant and a marker of acute and chronic inflammation.

The post Potential Dangers of High Ferritin Levels + How to Reduce It appeared first on SelfHacked.

What are Sulforaphane and Broccoli Sprouts?

Sulforaphane (SFN) is an isothiocyanate, a sulfur-containing organic compound [R, R].

It is found in cruciferous vegetables such as broccoli, cabbage, cauliflower, Brussels sprouts, and kale [R, R].

Sulforaphane is produced when glucoraphanin comes into contact with the enzyme myrosinase, contained within the same cells but in different compartments [R, R].

For example, cutting, chewing, or otherwise disrupting the broccoli plant cells initiates the production of sulforaphane. Compared to the stable glucoraphanin, sulforaphane begins degrading soon after production [R].

Three-day-old sprouts of certain cruciferous vegetables contain 10 to 100 times higher concentrations of glucoraphanin than in mature plants [R].

Levels of glucoraphanin and sulforaphane are highest in broccoli sprouts [R].

Sulforaphane has antioxidant, antimicrobial, anticancer, anti-inflammatory, anti-aging, neuroprotective, and anti-diabetic properties [R].

Sulforaphane also protects against cardiovascular and neurodegenerative diseases [R].

Apart from sulforaphane, broccoli sprouts contain many other bioactive, health-promoting compounds, such as gallic, chlorogenic, ferulic, sinapinic, benzoic and salicylic acids, quercetin, kaempferol, and vitamin C [R].

To learn about the many potential benefits of sulforaphane and sulforaphane-rich vegetables, check out this post.

Cancer Research

Prostate Cancer

Sulforaphane (in the form of broccoli sprout extract) boasts some relatively strong clinical evidence for a role in the prevention of prostate cancer and management strategies for preventing recurrence of prostate cancer.

In multiple clinical studies, men with recurrent prostate cancer who took 60 mg of sulforaphane per day had less prostate specific antigen (PSA, a marker used to measure prostate cancer progression) than those who did not take sulforaphane [R, R].

That being said, the FDA has not approved sulforaphane for the prevention of prostate cancer recurrence. Talk to your doctor before supplementing.

Research in Other Cancers

While studies have advanced the furthest for sulforaphane in prostate cancer, it is also under investigation for possible action against other types of cancer. Sulforaphane is considered a promising compound for a few reasons; not least of these is that people who eat sulforaphane-rich Brassica vegetables are significantly less

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What is Lipoic Acid?

Lipoic acid (LA), also known as alpha-lipoic acid (ALA), R-lipoic acid, or thioctic acid, is a disulfide-containing compound (R), found inside every cell of the body (R).

Some call it the “universal antioxidant” (R).

List of Important Functions for Lipoic Acid:

• Lipoic acid acts as a powerful antioxidant both inside and outside of the cells (R, R).
• Lipoic acid scavenges several reactive oxygen species (ROS) (R).
• Lipoic acid helps to regenerate both fat and water-soluble antioxidant vitamins (such as vitamins C and E) (R, R).
• Lipoic acid improves sugar and fat metabolism (R).
• Lipoic acid is an essential cofactor for mitochondrial respiratory enzymes that improves mitochondrial function (R). Lipoic acid exerts a “rejuvenating” impact on mitochondria by protecting them against the higher levels of ROS they produce during the aging process (R).
• Lipoic acid also has anti-inflammatory action, independently of its antioxidant activity (R).

Production of Lipoic Acid in the Human Body

A healthy body makes enough lipoic acid to supply its energy requirements; therefore, there is no daily requirement for this supplement. However, several medical conditions appear to be accompanied by low levels of lipoic acid – specifically, diabetes, liver cirrhosis, and heart disease (R).

In parts of Europe, lipoic acid is approved for the treatment of diabetic neuropathy. It has been shown to enhance insulin sensitivity, improve microcirculation in the limbs, and reduce neuropathic symptoms (R, R).

Also, lipoic acid produced in the body decreases with age, which could increase free radical-induced damage. Lipoic acid supplementation in animal models has also prolonged lifespan and prevented neurological damage (R).

Antioxidant Activity

Lipoic acid neutralizes free radicals and associated oxidative cellular damage (R, R).

Lipoic acid scavenges several reactive oxygen species (ROS) (R).

Lipoic acid also helps regenerate antioxidant vitamins C and E (R, R

The post What is Alpha-Lipoic Acid (ALA)? + Dosage & Side Effects appeared first on SelfHacked.

What is the Organic Acid Test (OAT)?

The Organic Acid Test, popularly known as OAT, measures the levels of organic compounds in urine that are produced in the body as a part of many vital biochemical pathways. It’s used to check for RARE inborn genetic defects of metabolism, most often in newborns.

A defect in a particular pathway can result in either accumulation or lowered levels of its byproducts. Thus, measuring the levels of these markers can help to identify which metabolic process is blocked or compromised.

However, OAT has been increasingly available as a pricy, direct-to-consumer test recommended by many alternative practitioners. In this article, we will break down the science behind testing neurotransmitter metabolites, which are found in the OAT, weighing in on whether they’re worth testing.

Neurotransmitter Metabolism Markers

Phenylalanine and Tyrosine Metabolites

The catecholamines – norepinephrine (noradrenaline), epinephrine (adrenaline), and dopamine – are released when the body is under physical or emotional stress. Their metabolites, vanillylmandelic acid (VMA) and homovanillic acid (HVA), also increase as a result.

Certain drugs (L-dopa, dopamine, epinephrine, and norepinephrine) that can be metabolized to HVA and VMA, may falsely elevate their levels in urine.

Proponents of OAT state that HVA and VMA can be elevated due to stress, from lead toxicity, due to the intake of L-DOPA, dopamine, phenylalanine, or tyrosine, or due to Clostridia metabolites. Elevated HVA/VMA is supposedly commonly caused by the by-products of the Clostridia bacteria.

1) Vanillylmandelic Acid (VMA)

VMA is the end product of the breakdown of ‘fight-or-flight’ hormones norepinephrine and epinephrine, also known as noradrenaline and adrenaline.

Adrenalin and noradrenalin are produced in the adrenal gland and released into the bloodstream. Their main role is to prepare the body for physical stress – they make the heart beat faster, increase blood pressure, expand the lungs, and increase energy supply by mobilizing energy stores in liver and fat cells [R].

Studies have found that VMA levels increase in response to severe stress and anxiety [R, R]. However, they increase only slightly.

Significant elevations in VMA levels are found in tumors, such as pheochromocytoma, a tumor of the adrenal gland or neuroblastoma, a nerve tissue cancer that occurs mainly in children [R, R]. This particular test

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What is the Organic Acid Test?

Organic Acid Test, popularly known as OAT, measures the levels of organic compounds in urine that are produced in the body as a part of many vital biochemical pathways.

A defect in a particular pathway can result in either accumulation or lowered levels of its byproducts. Thus, measuring the levels of these markers can help to identify which metabolic process is compromised.

Abnormal levels of organic acids not only signal issues with the metabolism, but excessive amounts of some organic acids can harm the body, which is why people with inborn metabolic disorders often need lifelong treatment.

Legitimate Use

Doctors will order an organic acids test to check for RARE inborn genetic defects of metabolism, most often in newborns. It’s frequently ordered as a follow-up for a positive newborn screen result, as recommended by American College of Medical Genetics and Genomics [R].

These tests are highly specialized and among the most complex tests performed in many laboratories. Performing the tests and interpreting the results requires highly trained and qualified health practitioners (American Board of Medical Genetics and Genomics or other relevant medical board-certified laboratory director) [R].

Usually, abnormal levels of a single organic acid can point to multiple anomalies. That’s why doctors will use a combination of markers to narrow down the potential root cause. They will focus on the overall pattern, rather than on individual abnormalities [R].

Furthermore, a characteristic abnormal organic acid profile is not always sufficient to establish a diagnosis. Confirmation by other tests is often required [R].

Unsanctioned Use

In recent years, some labs have started offering this test to the general public and many alternative practitioners started recommending it in their practice.

OAT testing has expanded to include “the diagnosis” of non-genetic conditions such as nutritional deficiencies or environmental exposure to toxins, which are then “treated” with supplements.

This type of testing also often includes another category of organic acids that are produced as a result of microbial activity (bacteria and yeast) in the gut that can supposedly uncover gut dysbiosis.

It’s important to know that there isn’t much scientific support for this kind of testing. That’s

The post Organic Acid Test (OAT): Is It Legit or A Hoax? appeared first on SelfHacked.

What is the Organic Acid Test?

Organic Acid Test, popularly known as OAT, measures the levels of organic compounds in urine that are produced in the body as a part of many vital biochemical pathways. It’s used to check for RARE inborn genetic defects of metabolism, most often in newborns.

A defect in a particular pathway can result in either accumulation or lowered levels of its byproducts. Thus, measuring the levels of these markers can help to identify which metabolic process is blocked or compromised.

However, OAT has been increasingly available as a pricy, direct-to-consumer test recommended by many alternative practitioners. In this article, we will break down the science behind testing for the glycolytic cycle, mitochondrial or Krebs cycle, and fatty acid metabolites. Read on to find out which ones are actually worth testing.

Carbohydrate Metabolism – Glycolytic Cycle Metabolites

Glycolysis is the first step in glucose metabolism (breakdown of sugar) producing pyruvate and some energy (ATP). This step takes place in the absence of oxygen. Pyruvate, then, enters mitochondria and is converted into acetyl CoA, which is then metabolized in the Krebs cycle to produce more energy in the presence of oxygen.

1) Pyruvic Acid (Pyruvate)

Pyruvic acid is created in the metabolism of carbs, proteins, and fats. It is one of the intermediate compounds our body uses to convert food into energy [R].

Apart from its role in energy metabolism, pyruvic acid is also an antioxidant and helps decrease inflammation [R].

When mitochondrial functions are compromised due to low oxygen supply or other factors, glycolysis becomes the major source of energy, producing more pyruvate. Excess pyruvate has an escape route where it is converted to oxaloacetate and lactic acid [R]. Thus, pyruvate levels are usually evaluated with levels of lactic acid and other organic acids.

A pyruvic acid test can tell you if there is a lack of oxygen in your body or issues with your blood vessels. A lactic acid (lactate) test, however, is more reliable and much more often used for these purposes.

These can increase pyruvate levels:

• Strenuous exercise [R, R, R]
• Migraines [R]
• Thiamine (vitamin B1) deficiency [R]
• Magnesium

The post OAT: Mitochondrial, Carb & Fatty Acid Metabolites appeared first on SelfHacked.

What is the Organic Acid Test?

Organic Acid Test, popularly known as OAT, measures the levels of organic compounds in urine that are produced in the body as a part of many vital biochemical pathways. It’s used to check for RARE inborn genetic defects of metabolism, most often in newborns.

A defect in a particular pathway can result in either accumulation or lowered levels of its byproducts. Thus, measuring the levels of these markers can help to identify which metabolic process is blocked or compromised.

However, OAT has been increasingly available as a pricy, direct-to-consumer test recommended by many alternative practitioners. In this article, we will break down the science behind testing amino acid metabolites, which are tested as a part of OAT, to find out if testing them has merit.

Amino Acid Metabolites

Low levels of amino acid metabolites are good. Higher levels mean there is impaired enzyme activity, most often due to genetic causes.

1) Keto and Hydroxy Derivatives of Amino Acids

Various markers can be included in this category, such as:

• 2-hydroxyisovaleric acid (2-HIV)
• 2-hydroxyisocaproic acid (2-HICA)
• 2-oxoisovaleric acid (alpha-ketoisovalerate)
• 2-oxoisocaproic acid (alpha-ketoisocaproate)
• 3-methyl-2-oxovaleric acid (2-Keto-3-methylvaleric acid or alpha-keto-beta-methylvalerate)

All of them are metabolites of branched-chain amino acids (BCAA) leucine, isoleucine, and valine [R].

These can increase keto and hydroxy metabolites of amino acids:

• Protein meals; habitual intake of lots of red and processed meat and eggs, and BCAA supplements [R, R]
• Exercise (short-term) (2-HIV) [R]
• Prolonged fasting [R]
• Alcoholism (2-HIV) [R]
• Disturbances in blood pH (lactic acidosis, ketoacidosis) [R, R, R]
• Primary biliary cirrhosis, an autoimmune liver disease [R]
• Bacterial dysbiosis in short bowel syndrome (2-HICA) [R, R]
• Peroxisomal diseases, such as Zellweger syndrome (due to bacterial dysbiosis) (2-HICA) [R]
• Rare inborn metabolic disorders such as maple syrup urine disease and dihydrolipoyl dehydrogenase deficiency [R, R, R, R, R, R, R]

People who can’t process branched-chain amino acids (BCAAs) are usually put on a low protein

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Ketones vs. Ketone Bodies

What Are Ketones?

Ketones are organic compounds that contain a carbon-oxygen double bond (carbonyl group) that is single bonded to 2 hydrocarbon groups [R].

They are found nearly everywhere in both industry and nature.

In industry, ketones are used as chemical building blocks to make explosives, paints, and textiles [R, R].

Ketones are used in natural and synthetic pharmaceutical products. These include antibiotics and steroid hormones (cortisone) [R, R].

In nature, ketones are found in many sugars (ketoses), including fructose, and hormones (progesterone and testosterone) [R, R, R].

Plant-based ketones are known for their sweet smell. They are present in vanilla, cinnamon, almond, and mint extracts [R].

Finally, the blue cheese gets its sharp smell from a group of methyl ketones [R].

Ketone Bodies

Although “ketones” and “ketone bodies” are often used interchangeably, not all ketones are ketone bodies. Neither are all ketone bodies technically ketones.

Ketone bodies are produced naturally in the liver by the breakdown of fatty acids. When we say ketone bodies, we refer to [R, R]:

• Acetone
• Acetoacetic acid (AcAc)
• Beta-hydroxybutyric acid (BHB) – not technically a ketone

Ketone bodies act as an alternate energy source when carbs are not available because of fasting or prolonged exercise [R].

Beta-hydroxybutyric acid and acetoacetate easily pass through membranes and are a source of energy for the body and the brain [R].

Mechanism of Action

In the absence of carbohydrates and when glycogen (glucose) stores are depleted, fats move to the liver. Fats are broken down into glycerol and fatty acid molecules. Fatty acids are then converted into ketone bodies by a process called ketogenesis [R].

Ketogenesis primarily occurs in the mitochondria of liver cells [R].

Acetoacetate is the precursor to the other 2 ketone bodies, acetone and beta-hydroxybutyric acid [R].

Ketone bodies move to

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What is CYP3A5?

CYP3A5 is one of the cytochrome P450 monooxygenases (CYPs). These are enzymes that eliminate most of the drugs and toxins from the human body [R].

Function

This enzyme is very similar in structure and function to CYP3A4. However, unlike CYP3A4, its activity varies greatly between people, and many actually don’t have a functional version of this enzyme [R].

The enzyme is functional in most Africans but in few Whites [R].

In people who do have this enzyme, it can represent over 50% of the total liver CYP3A activity [R].

This enzyme metabolizes:

• Antihypertensive drugs: felodipine [R] and nifedipine [R].
• Immune suppressants: sirolimus [R], tacrolimus [R, R] and cyclosporine A [R].
• Antiemetics: granisetron [R].
• Anticancer drugs: lapatinib [R] and vincristine [R].
• TNF inhibitors: etanercept [R].
• Cholesterol-lowering drugs: simvastatin and atorvastatin [R]
• Sedatives midazolam and alprazolam (Xanax) [R].
• Antibiotic erythromycin [R].
• Antiretroviral drugs: saquinavir [R].

Location

This enzyme is found in various tissues, especially the liver, kidney, and lungs [R, R].

It plays an important function in the kidneys and may be related to blood pressure [R].

Roles in Health

This enzyme may act as a tumor suppressor. Lower enzyme levels may be associated with more aggressive hepatocellular carcinoma (liver cancer), quicker disease recurrence after treatment, and worse overall patient survival [R].

Roles in Disease

This enzyme may promote prostate cancer cell growth. In a study of 873 Japanese women, those with the functional enzyme had higher rates of breast cancer [R, R].

In a trial of 385 subjects, a nonfunctional enzyme variant was associated with higher rates of acute and chronic leukemia [R].

Genetics

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What is CYP2E1?

CYP2E1 is one of the cytochrome P450 monooxygenases (CYPs). These are enzymes that eliminate most of the drugs and toxins from the human body (R).

Function

This enzyme metabolizes:

• Small organic molecules such as alcohol, acetone, and pyrazole (R, R).
• Fatty acids, ketone bodies, and glycerol (R, R).
• Clinically-used drugs such as salicylic acid, halothane, isoniazid, and isoflurane (R), Tylenol (paracetamol/acetaminophen) (R), and phenobarbital (R).
• Toxic chemicals including carbon tetrachloride and chloroform (R).
• Cancer-causing agents present in the diet and tobacco smoke, such as nitrosamines, aniline, and benzopyrene (R, R).
• Environmental toxins such as benzene, and acrylamide (R).

Location

This enzyme is found in various tissues including the brain, lungs, and kidneys. It is most concentrated in the liver (R).

The enzyme is responsible for approximately 20% of alcohol metabolism in the brain (R).

Roles in Health

CYP2E1 is responsible for the detoxification of environmental pollutants (R).

Although some studies suggest CYP2E1 activity is implicated in Parkinson’s disease, other studies show that CYP2E1 brain activity is beneficial. This enzyme can have beneficial effects due to its removal of neurotoxins related to Parkinson’s, such as heavy metals and pesticides (R).

Roles in Disease

This enzyme converts alcohol to acetaldehyde, a known cancer-causing agent. However, the enzyme is induced only at high, chronic levels of alcohol consumption (R, R, R).

CYP2E1 activity is associated with alcohol-induced liver injury in mice and neurodegeneration in rats (R, R).

CYP2E1 deficient mice are resistant to alcohol-induced gut leakiness and liver inflammation (R).

The activity of this enzyme contributes to the damage seen in mice with diabetes, fatty liver, and obesity (R, R).

CYP2E1 deficient mice have higher insulin sensitivity and better glucose tolerance. They are also protected from weight gain and

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What is CYP2C19?

CYP2C19 is one of the cytochrome P450 monooxygenases (CYPs). These are enzymes that eliminate most of the drugs and toxins from the human body (R).

Read more about CYPs here.

This enzyme is responsible for processing more than 25 clinically important drug groups. It clears about 10% of commonly used clinical drugs that undergo Phase I detoxification (R).

Function

This enzyme metabolizes:

• Antidepressants: citalopram, escitalopram (R, R), amitriptyline (R), and sertraline (R)
• Proton pump inhibitors: omeprazole (R)
• Anticonvulsants: mephenytoin (R)
• Diazepam (R)
• Methadone (R)
• Antimalarial proguanil (R)
• Anticoagulant warfarin (R)
• Antiplatelet clopidogrel (Plavix) (R)
• Antifungal voriconazole (R)
• MDMA (ecstasy) (R)

This enzyme is found in the liver. However, it is also active in the fetal brain, with a possible role in brain development (R).

Beneficial Effects

This enzyme participates in converting arachidonic acid to epoxyeicosatrienoic acids (EETs). EETs have beneficial effects on the heart and blood vessels.

Low enzyme activity was associated with heart disease in a study of 162 subjects (R).

Detrimental Effects

High CYP2C19 activity was associated with depression and smaller hippocampus volume in a study of 1418 volunteers (R).

A study of 1472 subjects in Sweden showed that people with high enzyme activity (CYP2C191 carriers) were more likely to be diagnosed with depression than those with defective enzyme function (CYP2C192 carriers) (R).

CYP2C19 deficiency was associated with a lower prevalence of major depressive disorder and lower depression severity in a study of 3848 African-Americans (R).

Among 209 people with depression who had attempted suicide, those with high enzyme activity showed higher suicidality (R).

Mice with high enzyme activity have impaired serotonin and BDNF production in the hippocampus (R).

Gene Polymorphism

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What is CYP2C9?

CYP2C9 is one of the cytochrome P450 monooxygenases (CYPs). These are enzymes that eliminate most of the drugs and toxins from the human body (R).

Read more about CYPs here.

CYP2C9 is responsible for the metabolic clearance of up to 15-20% of all drugs undergoing Phase I detoxification (R).

This enzyme is the third most important cytochrome P450 (CYP) in terms of the number of drugs metabolized (R).

CYP2C9 Function

This enzyme metabolizes:

• Antidiabetics: tolbutamide (R), nateglinide (R) and glipizide (R)
• Antiepileptics: phenytoin (R) and valproate (R). CYP2C9 is responsible for about 90% of phenytoin metabolism (R)
• Antihypertensive losartan (R, R)
• Cannabinol (R)
• Non-steroidal anti-inflammatory drugs (NSAIDs): flurbiprofen (R), ibuprofen (R, R), and celecoxib (R)
• Anticoagulants: warfarin, acenocoumarol, phenprocoumon (R, R)
• Anti-asthmatic zafirlukast (R)
• Cholesterol-lowering fluvastatin (R)

CYP2C9 also metabolizes many hormones and other compounds, such as progesterone, testosterone and arachidonic acid (R).

This enzyme is primarily found in the liver (R), heart and blood vessels (R).

CYP2C9 accounts for about 20% of the total liver CYP content (R).

Beneficial Effects

In the human heart, CYP2C9 produces epoxyeicosatrienoic acids (EETs) from arachidonic acid (R).

EETs have a protective effect on blood vessels, including vasodilatation (widening of the blood vessels), anti-inflammatory, and antithrombotic effects. They are also believed to protect the heart by increasing post-ischemic (low oxygen) function and reducing heart infarct size (R).

People with higher CYP2C9 activity were less likely to develop colorectal adenoma (colon cancer) in a study of 928 subjects (R). This suggests that the activity of this enzyme is protective against cancer.

Detrimental Effects

This enzyme can activate some

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What is the Organic Acid Test?

Organic Acid Test, popularly known as OAT, measures the levels of organic compounds in urine that are produced in the body as a part of many vital biochemical pathways. It’s used to check for RARE inborn genetic defects of metabolism, most often in newborns.

A defect in a particular pathway can result in either accumulation or lowered levels of its byproducts. Thus, measuring the levels of these markers can help to identify which metabolic process is blocked or compromised.

However, OAT has been increasingly available as a pricy, direct-to-consumer test recommended by many alternative practitioners. In this article, we will break down the science behind testing for detoxification markers and oxalate metabolism markers. One of these tests is more useful than the others. Read on to find out more.

Detoxification Markers

According to OAT proponents, low is good for detoxification markers. Higher levels indicate there’s toxic exposure and/or increased oxidative stress.

1) 2-Methylhippuric Acid

Methylhippuric acid (2-methylhippurate) has been used as a marker of xylene exposure [R, R, R].

Common sources for xylene exposure are paint thinners, building products, fuel, exhaust fumes, and industrial solvents.

Unless you are exposed to xylene at work, this test will likely be of limited benefit to you.

2) Orotic Acid

Orotic acid is produced in the body as an intermediate compound in pyrimidine metabolism. Levels increase in many inborn errors of the urea cycle, when there is excess ammonia (hyperammonemia). It also increases in a number of other disorders involving arginine metabolism [R, R].

High orotic acid levels can be caused by:

• Arginine deficiency [R, R, R]
• Refeeding after fasting [R]
• Impaired liver function due to alcohol, drugs (such as valproic acid), liver disease or viral liver infection [R, R, R, R, R, R]
• Physical trauma [R]
• Inborn errors of urea cycle metabolism [R, R]

If your levels are abnormal, work with your doctor to

The post Organic Acid Test (OAT): Detoxification and Oxalates appeared first on SelfHacked.

What is the Organic Acid Test?

Organic Acid Test, popularly known as OAT, measures the levels of organic compounds in urine that are produced in the body as a part of many vital biochemical pathways. It’s used to check for RARE inborn genetic defects of metabolism, most often in newborns.

A defect in a particular pathway can result in either accumulation or lowered levels of its byproducts. Thus, measuring the levels of these markers can help to identify which metabolic process is blocked or compromised.

However, OAT has been increasingly available as a pricey, direct-to-consumer test recommended by many alternative practitioners. In this article, we will break down the science behind testing for particular nutrient deficiencies that OAT tests for, weighing in on whether they make sense.

B vitamins and Other Nutritional markers

1) Methylmalonic acid (Vitamin B12 Marker)

Methylmalonic acid (MMA) is a legitimate functional indicator of vitamin B12 deficiency. That’s because vitamin B12 is required for MMA to be converted to succinyl-CoA. When B12 is low, MMA levels in the blood and urine increase [R].

Methylmalonic acid levels increase in the early stages of vitamin B12 deficiency, when total vitamin B12 levels may still be in the normal range. Therefore, measuring MMA can tell you if you have a mild vitamin B12 deficiency [R].

Elevated MMA levels can be caused by:

• Vitamin B12 deficiency [R]
• Small bowel bacterial overgrowth (SIBO) in short bowel syndrome [R]
• Common harmless genetic mutations [R]
• Genetic disorders (methylmalonic acidemia) [R]
• Aging [R, R]

Levels can be low in kidney disease, even when vitamin B12 deficiency is present [R].

If you have high MMA levels, work with your doctor to find out what’s causing them – your doctor will likely order a vitamin B12 test for confirmation. Many older people have high MMA irrespective of vitamin B12 levels [R, R].

2) Pyridoxic acid (Vitamin B6 Marker)

Pyridoxic acid is the product of vitamin B6 breakdown. Vitamin B6 is needed for more than 160 different metabolic reactions within the body. It works with B6-dependent enzymes, which are important for amino acid production and

The post Organic Acid Test (OAT): Nutrient Deficiencies & Methylation appeared first on SelfHacked.

What is Lactobacillus brevis?

Lactobacillus brevis is a plant-derived lactic acid bacterium isolated from ‘Suguki’, a traditional Japanese pickle produced in Kyoto (R).

L. brevis can be found in fermented foods such as sauerkraut and pickles. It is also a normal part of the human gut microbiota.

Health Benefits of L. brevis

L. brevis probiotic 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. Speak with your doctor before supplementing.

Possibly Effective For

1) Immunity

L. brevis reduced the incidence of influenza in 1089 elementary school children. The improvement was especially pronounced in unvaccinated individuals (R).

Oral administration of live, but not heat-killed, L. brevis significantly increased IFN-α production in 60 volunteers. The intake tended to be most beneficial in subjects with initially low levels of IFN-α production (R).

L. brevis alleviated influenza virus infection symptoms in mice (R).

L. brevis enhanced cytotoxic activity of mouse splenocytes (R).

L. brevis exhibited antiviral activity towards herpes virus (HSV-2) and inhibits HSV-2 multiplication (R).

2) Dental Health

L. brevis improved oral pH, reduced salivary Streptococcus mutans, and reduced bleeding on probing in 191 high caries risk schoolchildren (R).

L. brevis had anti-inflammatory effects and brought about the total disappearance or amelioration of clinical symptoms in 8 healthy subjects and 21 patients with periodontitis (R).

L. brevis exerted oral anti-inflammatory properties, possibly by preventing nitric oxide synthesis, in 34 healthy adults (R).

L. brevis inhibited periodontal inflammation, significantly decreased bone loss and lowered the count of anaerobic bacteria in mice with periodontitis (R).

3) Gut Health

Constipation

Heat-killed L. brevis improved intestinal function in 32 women with constipation and promoted the growth of Bifidobacteria (R).

Marked enhancement of NK-cell activity and improved bowel symptoms were observed in 44 female students with constipation, who consumed pickles containing dead L. brevis cells (R).

The post Could L. brevis Improve Your Health? Immunity, Gut, & More appeared first on SelfHacked.

What is Lactobacillus johnsonii?

Lactobacillus johnsonii is a lactic acid bacterium that resides in the human gastrointestinal tract where it aids in polysaccharide and protein digestion and also generates a variety of nutrients, including vitamins and short-chain fatty acids. L. johnsonii also plays a role in the fermentation and preservation of various food items.

Health Benefits of L. johnsonii

L. johnsonii probiotic 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. Speak with your doctor before supplementing.

Possibly Effective For

1) H. pylori

L. johnsonii was inversely associated with H. pylori colonization in 621 children (R, R) and in 12 asymptomatic volunteers (R).

Fermented milk containing L. johnsonii co-administered with antibiotics was shown to have a favorable effect on H. pylori gastritis in 50 volunteers (R).

During the early infection stages, administration of L. johnsonii attenuated H. pylori-induced gastritis in mice (R).

Both live and heat-killed L. johnsonii inhibited the growth of H. pylori in mice, where they also suppress gastric acid secretion (R).

Insufficient Evidence For

The following purported benefits are only supported by limited, low-quality clinical studies. There is insufficient evidence to support the use of L. johnsonii probiotics for any of the below-listed uses. Remember to speak with a doctor before taking L. johnsonii probiotics, and never use them in place of something your doctor recommends or prescribes.

2) Gut Microbiota

Fermented milk with L. johnsonii increased total Bifidobacteria and Lactobacilli and decreased lecithinase-positive Clostridium in 22 women (R).

L. johnsonii intake increased the populations of C. histolyticum, Lactobacilli, and Bifidobacteria, and decreased those of F. prausnitzii in 8 volunteers (R).

3) Immunity

Fermented milk containing L. johnsonii reduced the rate of infections in 24 elderly, hospitalized patients (R).

L. johnsonii helps recover nutritional status and systemic immune responses in aged mice (R).

L. johnsonii inhibits the growth of Helicobacter

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Phase III Detoxification

Recap: Detox Phases

Our bodies process and remove these foreign chemicals (xenobiotics) thanks to our efficient detoxification mechanisms. These mechanisms also deal with metabolic products such as excess hormones (endobiotics).

“Enzymes of detoxification” are a big family of enzymes that alter foreign chemicals and metabolic waste either by making them more readily excretable or less pharmacologically active (R).

The detoxification process can be roughly divided into three phases (R):

• Phase I is governed by transformation enzymes – these enzymes oxidize, reduce and hydrolyze toxins/drugs
• Phase II is managed by conjugation enzymes – these enzymes conjugate Phase I products
• Phase III is carried out by transport proteins – these proteins transport the final products from the cell

Transporters Eliminate Toxins from Cells

ABC Transporters

Phase III of detoxification is responsible for eliminating toxins and metabolic products from cells.

Phase III transporters can be found in the liver, intestine, kidney, and brain, where they act as a barrier against drug entry, and manage endobiotic and xenobiotic absorption, distribution, and excretion (R).

These transporters are called ABC transporters (ATP-binding cassette transporters) (R), and they require ATP to transport a broad range of compounds across the cell membrane (R). Some of these transporters are also called multidrug resistance proteins (MRPs), because of their involvement in multidrug resistance (R).

Bile Secretion

Note that, although not officially a part of the 3 -phase detoxification process, bile secretion is necessary for the elimination of toxic endo- and xenobiotics such as bilirubin, lipid bacteria products (endotoxin), and several inflammatory mediators. These products are removed through the intestines (R).

Impairment of bile flow may result in a buildup of liver toxins and liver injury.

Dietary Factors that May Improve Bile Flow

Yarrow (Achillea millefolium) and artichoke may stimulate bile flow (R, R), as may potentially cumin, ajowan, garlic and ginger (R, R).

Heavy Metals Detoxification

The post The Science of Detoxification: Phase III & Detox Nutrients appeared first on SelfHacked.

Phase II Detoxification

Recap: Detox Phases

Our bodies process and remove these foreign chemicals (xenobiotics) thanks to our efficient detoxification mechanisms. These mechanisms also deal with metabolic products such as excess hormones (endobiotics).

“Enzymes of detoxification” are a big family of enzymes that alter foreign chemicals and metabolic waste either by making them more readily excretable or less pharmacologically active (R).

The detoxification process can be roughly divided into three phases (R):

• Phase I is governed by transformation enzymes – these enzymes oxidize, reduce and hydrolyze toxins/drugs
• Phase II is managed by conjugation enzymes – these enzymes conjugate Phase I products
• Phase III is carried out by transport proteins – these proteins transport the final products from the cell

Phases I, II, and III must work in unison for the proper removal of unwanted toxins, drugs, and excess hormones.

Enzymatic Conjugation Reduces the Toxicity of Phase I Products

Through phase I transformation, the fat-soluble toxin is converted into a more water-soluble form. However, phase I reactions are not always sufficient to make the toxin water-soluble enough and in many cases, they render the products more reactive, which makes the toxins potentially more destructive. This is where the phase II enzymes kick in (R).

Phase II enzymes increase the solubility and reduce the toxicity of phase I products (R).

Scientists think they play a major role in the cellular detoxification of damaging, genotoxic and carcinogenic chemicals (R).

Gene polymorphisms and/or a lack of these enzymes have been suggested to play a role in several forms of cancer, though far more research is needed to verify this link (R).

Phase II Enzymes

Phase II enzymes contain several superfamilies of conjugating enzymes. Among the most important ones are (R):

• UDP-glucuronosyltransferases (UGT)
• Glutathione S-transferases (GST)
• Sulfotransferases (SULT)
• N-acetyltransferases (NAT), and
• Methyltransferases (MT).

UDP-glucuronosyltransferases (UGTs)

UDP-glucuronosyltransferases (UGTs) are responsible for the glucuronidation reaction, one of the most important detoxification pathways of the Phase II transformation (R).

UGT enzymes are responsible for the metabolism of many xenobiotics (drugs, chemical carcinogens, environmental pollutants, and dietary substances) and endobiotics (bilirubin, steroid hormones, thyroid hormones, bile acids, and fat-soluble vitamins) (R

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Disclaimer: Salvia is illegal in many states in the U.S and is a controlled substance in several countries. We highly advise against the use of salvia until future studies determine its safety and efficacy in medically-supervised and safe settings. The only aim of this post is to outline the research findings.

What is Salvia Divinorum?

Salvia divinorum (also known as Sage of the Diviners, Seer’s Sage, Yerba de la Pastora, Ska Maria, or simply salvia) is a plant species known for its hallucinogenic effects due to psychoactive compounds in its leaves.

Native groups from Mexico have long used this plant in their rituals and as a traditional remedy [R].

Salvia has gained recent popularity as a recreational drug. Street names for this plant include Magic Mint, Purple Sticky, Lady Salvia, and Sally D [R].

Salvia is not considered a controlled substance in the United States, but it has been made illegal in several states. In many other countries, salvia is illegal [R].

History

The salvia plant is native to the sierras of Oaxaca, Mexico. The Mazatec tribe who are native to the region have long used the plant in religious ceremonies and as a medicine for various conditions including headaches, joint pain, and arthritis pain [R, R].

In the 1970s, it was reported that young people from cities in Mexico were traveling to the Sierra Mazateca to purchase Salvia divinorum from the native tribes to make into cigarettes and smoke as a substitute for marijuana [R].

Use in the United States appears to have grown steadily during the 1990s. According to the National Survey on Drug Use and Health, the lifetime prevalence of salvia use increased from 0.7% to 1.3% from 2006 to 2008 [R].

Legal Status

The following section describes the legal status of salvia in different countries. Laws are complex and constantly changing, do not use this information as legal advice. Always verify your own local regulations.

United States

Currently, in the United States, salvia is not a controlled substance on the federal level, although there have been multiple attempts to make salvia and its active compound a Schedule I substance [R].

However, 29 states have made salvia and/or salvinorin A (the active compound in salvia) illegal or

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